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Blood volume in the rat
Abstract
The organ distribution of radiopharmaceuticals in the rat is usually estimated using 7% of body weight (BW) for blood volume (BV). In spite of its important impact on the evaluation of new agents, this value has not been validated adequately. We therefore studied blood volume in 70 awake Wistar rats (100 to 400 g BW) in which red blood cell volume (RBCV) and plasma volume (PV) were measured simultaneously. Red blood cell volume was measured by in vitro RBC-tagging with Tc-99m in Sn-pyrophosphate, 0.05 microgram per ml of blood; plasma volume was measured with I-125 human serum albumin (HSA). Ten minutes after injection of the dose, 0.5 ml of blood was withdrawn from the carotid or femoral artery and duplicate samples of 0.025 ml of blood were counted after separating RBCs from plasma. Total blood volume was calculated by adding RBC volume and plasma volume. The relationship for the entire group was: BV (ml) = 0.06 X BW + 0.77 (r = 0.99, n = 70, p less than 0.001). The difference between male and female rats was not statistically significant. The use of an arbitrary value of 7% for estimation of blood volume can lead to significant errors in calculating radiopharmaceutical distribution. The use of the general formula for the blood-volume calculation described here should improve the accuracy and reliability of estimates of radiopharmaceutical distribution.
... The dose of human omentin-1 used in the present study (18 µg/kg) is assumed to be approximately 270 ng/mL in blood, based on the estimation that the circulating blood volume is 62 × {BW (kg) + 0.02} (mL) in rats with BW ≥ 120 (g) [15]. Since this concentration was close to 300 ng/mL at which human omentin-1 had previously shown protective effects on cardiovascular cells in vitro [16][17][18], it was determined to be the appropriate dose. ...
... It was also reported that the serum concentration of human omentin-1 decreased to 72.19 ± 54.33 ng/mL in stage 1 hypertensive patients (140 ≤ SBP ≤ 159 mm Hg and 90 ≤ diastolic blood pressure; DBP ≤ 99 mm Hg) or to 62.45 ± 47.01 ng/mL in stage 2 hypertensive patients (160 ≤ SBP ≤ 179 mm Hg and 100 ≤ DBP ≤ 109 mm Hg) compared with 147.84 ± 58.55 ng/mL in normotensive humans (SBP ≤ 139 mm Hg and DBP ≤ 90 mm Hg) [8]. Similarly, the blood concentration of omentin-1 in rats was reported to be approximately 90 ng/mL in the serum of Zucker lean rats heterozygous for the mutant leptin receptor gene fa (lean Zucker fa/+ ), while it decreased to approximately 30 ng/mL in the serum of Zucker Diabetic Fatty rats (ZDF) homozygous for the fa mutant gene (obese The dose of human omentin-1 used in the present study (18 μg/kg) is assumed to approximately 270 ng/mL in blood, based on the estimation that the circulating blood v ume is 62 × {BW (kg) + 0.02} (mL) in rats with BW ≥ 120 (g) [15]. Since this concentrat was close to 300 ng/mL at which human omentin-1 had previously shown protective fects on cardiovascular cells in vitro [16][17][18], it was determined to be the appropriate do It was also reported that the serum concentration of human omentin-1 decreased to 72 ± 54.33 ng/mL in stage 1 hypertensive patients (140 ≤ SBP ≤ 159 mm Hg and 90 ≤ diasto blood pressure; DBP ≤ 99 mm Hg) or to 62.45 ± 47.01 ng/mL in stage 2 hypertensive tients (160 ≤ SBP ≤ 179 mm Hg and 100 ≤ DBP ≤ 109 mm Hg) compared with 147.84 ± 58 ng/mL in normotensive humans (SBP ≤ 139 mm Hg and DBP ≤ 90 mm Hg) [8]. ...
Hypertension is one of the major risk factors for cardiovascular diseases and is caused by various abnormalities including the contractility of blood vessels. Spontaneously hypertensive rats (SHR), whose systemic blood pressure increases with aging, are a frequently used animal model for investigating essential hypertension and related complications in humans due to the damage of several organs. Human omentin-1 is an adipocytokine consisting of 313 amino acids. Serum omentin-1 levels decreased in hypertensive patients compared with normotensive controls. Furthermore, omentin-1 knockout mice showed elevated blood pressure and impaired endothelial vasodilation. Taken together, we hypothesized that adipocytokine, human omentin-1 may improve the hypertension and its complications including heart and renal failure in the aged SHR (65–68-weeks-old). SHR were subcutaneously administered with human omentin-1 (18 μg/kg/day, 2 weeks). Human omentin-1 had no effect on body weight, heart rate, and systolic blood pressure in SHR. The measurement of isometric contraction revealed that human omentin-1 had no influence on the enhanced vasocontractile or impaired vasodilator responses in the isolated thoracic aorta from SHR. On the other hand, human omentin-1 tended to improve left ventricular diastolic failure and renal failure in SHR. In summary, human omentin-1 tended to improve hypertensive complications (heart and renal failure), while it had no influence on the severe hypertension in the aged SHR. The further study of human omentin-1 may lead to the development of therapeutic agents for hypertensive complications.
... after oral cnicin application (80 µg/mouse) determined by LC-MS. Data represent mean ± SEM (bars) and single values (dots) of individual animals. of distribution of cnicin was 10.6 ml, corresponding to the plasma volume of rats (300 g) (Lee and Blaufox, 1985). Cnicin apparent terminal elimination half-life, calculated from parameter point estimates for the terminal (β) slope of the concentration vs. time curve via microconstants, was about 12.7 min (Gabrielsson and Hjorth, 2016). ...
... Serum was harvested from the whole blood for biochemical analysis of tumour marker: CEA using Enzyme Linked Immunosorbent Assay (ELISA) method (Wild, 1994). However; the total blood volume (TBV) and plasma volume (PV) were calculated as described by Lee and Blaufox (1985) and Bijsterbosch et al. (1981) respectively. TBV (ml) = 0.06 × BW × 0.77 PV (ml) = 0.0291 * BW + 2.54 ...
... The human dose was obtained from published literature and converted to the rat dose using the formula animal dose in mg kg −1 = human equivalent dose in mg kg −1 × 6.2 [62]. Using 20 mL as the blood volume of a 300 g rat as standard [63], the drug concentrations were calculated for the 360 µL capacity of the TEG cup. ...
Centhaquine is a novel vasopressor acting on α2A- and α2B-adrenoreceptors, increasing venous return and improving tissue perfusion. We investigated the effects of centhaquine on blood coagulation in normal state and uncontrolled hemorrhage using ex vivo and in vivo experiments in different species. Thromboelastography (TEG) parameters included clotting time (R), clot kinetics [K and angle (α)], clot strength (MA), and percent lysis 30 min post-MA (LY30). In normal rat blood, centhaquine did not alter R, K, α, MA, or LY30 values of the normal vehicle group or the antithrombotic effects of aspirin and heparin. Subsequently, New Zealand white rabbits with uncontrolled hemorrhage were assigned to three resuscitation groups: Sal-MAP 45 group (normal saline to maintain a mean arterial pressure, MAP, of 45 mmHg), Centh-MAP 45 group (0.05 mg kg−1 centhaquine plus normal saline to maintain a MAP of 45 mmHg), and Sal-MAP 60 group (normal saline to maintain a MAP of 60 mmHg). The Sal-MAP 45 group was characterized by no change in R, reduced K and MA, and increased α. In the Centh-MAP 45 group, TEG showed no change in R, K, and α compared to saline; however, MA increased significantly (p = 0.018). In the Sal-MAP 60 group, TEG showed no change in R, an increase in α (p < 0.001), a decrease in K (p < 0.01), and a decrease in MA (p = 0.029) compared to the Centh-MAP 45 group. In conclusion, centhaquine does not impair coagulation and facilitates hemostatic resuscitation.
... Changes in the estimated plasma volume were calculated using the Strauss formula as follows: Hb baseline/Hb 6 months × [(100 -Ht 6 months) / (100 -Ht baseline) -1] × 100 (33). The Strauss formula was used as a proxy to assess the traditional human and rodent plasma volume measurements with 125 I-human serum albumin (20,34,35). Serum osmolarity was calculated using the following formula: 2 × serum Na + (mEq/L) + plasma glucose (mg/dL) / 18 + blood urea nitrogen (mg/dL) / 2.8 (4,36). ...
Sodium glucose cotransporter 2 (SGLT2) inhibitors have both glucose-lowering and diuretic effects. We recently reported that the SGLT2 inhibitor dapagliflozin exerts short-term fluid homeostatic action in patients with chronic kidney disease (CKD). However, the long-term effects of SGLT2 inhibitors on body fluid status in patients with CKD remain unclear. This was a prospective, non-randomized, open-label study that included a dapagliflozin treatment group ( n = 73) and a control group ( n = 24) who were followed for 6 months. Body fluid volume was measured using a bioimpedance analysis device. The extracellular water-to-total body water ratio (ECW/TBW), a predictor of renal outcomes, was used as a parameter for body fluid status (fluid retention, 0.400 ≤ ECW/TBW). Six-month treatment with dapagliflozin significantly decreased ECW/TBW compared with the control group (−0.65% ± 2.03% vs. 0.97% ± 2.49%, p = 0.0018). Furthermore, dapagliflozin decreased the ECW/TBW in patients with baseline fluid retention, but not in patients without baseline fluid retention (−1.47% ± 1.93% vs. −0.01% ± 1.88%, p = 0.0017). Vasopressin surrogate marker copeptin levels were similar between the control and dapagliflozin groups at 6 months (32.3 ± 33.4 vs. 30.6 ± 30.1 pmol/L, p = 0.8227). However, dapagliflozin significantly increased the change in copeptin levels at 1 week (39.0% ± 41.6%, p = 0.0010), suggesting a compensatory increase in vasopressin secretion to prevent hypovolemia. Renin and aldosterone levels were similar between the control and dapagliflozin groups at 6 months, while epinephrine and norepinephrine (markers of sympathetic nervous system activity) were significantly lower in the dapagliflozin group than in the control group. In conclusion, the SGLT2 inhibitor dapagliflozin ameliorated fluid retention and maintained euvolemic fluid status in patients with CKD, suggesting that SGLT2 inhibitors exert sustained fluid homeostatic actions in patients with various fluid backgrounds.
Clinical trial registration: https://www.umin.ac.jp/ctr/ , identifier [UMIN000048568].
... The dose of human omentin-1 used in the present study (18-21 µg/kg) was assumed to be approximately 270-330 ng/ ml (7.71-9.43 nM) in blood based on the estimation that the circulating blood volume is 62 × {BW (kg) + 0.02} (ml) in rats with BW ≥ 120 (g) (Lee and Blaufox 1985). ...
Purpose
Hypertension is one of the major risk factors for renal failure and cardiovascular diseases, and is caused by various abnormalities including the contractility of blood vessels. Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which mimic human type 2 diabetes, are frequently used to study obesity-induced insulin resistance (IR) and hypertension. Human omentin-1 is one of the recently identified adipocytokines. We previously demonstrated that human omentin-1 not only caused vasodilation in rat isolated blood vessels, but also prevented inflammatory responses, a possible mechanism relating IR, in human vascular endothelial cells. Taken together, we hypothesized that human omentin-1 may reduce obesity-induced IR and hypertension in OLETF rats.
Methods
OLETF rats were intraperitoneally administered with human omentin-1 for 7 days.
Results
Human omentin-1 had no influence on overweight, hyperglycemia, urinary glucose extraction, hyperinsulinemia, and systemic IR in OLETF rats. Human omentin-1 decreased systolic blood pressure in OLETF rats. The measurement of isometric contraction revealed that human omentin-1 had no influence on the agonist-induced contractile and relaxant responses in isolated thoracic aorta from OLETF rats. However, the relaxant response mediated by human insulin was converted into the contractile response in thoracic aorta from OLETF rats, which was prevented by human omentin-1. The Western blotting revealed that human omentin-1 improved the decrease in endothelial nitric oxide synthase activation in isolated thoracic aorta from OLETF rats.
Conclusion
In summary, we for the first time revealed that human omentin-1 partly reduces vascular IR and thereby inhibits hypertension in OLETF rats.
... A separate sample of blood was placed in a Microtainer plasma separation tube in order to estimate content of [ 203 Hg] in plasma and cellular fractions. The total volume of blood was estimated to be 6 % of body weight (Lee and Blaufox, 1985). ...
Mercury (Hg) is an important environmental toxicant to which humans are exposed on a regular basis. Mercuric ions within biological systems do not exist as free ions. Rather, they are bound to free sulfhydryl groups (thiols) on biological molecules. Metallothionein (MT) is a cysteine-rich, metal-binding protein that has been shown to bind to heavy metals and reduce their toxic effects in target cells and organs. Little is known about the effect of MT on the handing and disposition of Hg. Therefore, the current study was designed to test the hypothesis that overexpression of MT alters the corporal disposition of Hg and reduces its nephrotoxicity. Furthermore, the current study examined the transport of Hg-MT complexes in isolated proximal tubules. Rats were treated with saline or Zn followed by injection with a non-nephrotoxic (0.5 µmol kg⁻¹), moderately nephrotoxic (1.5 µmol kg⁻¹), or significantly nephrotoxic (2.25 µmol kg⁻¹) dose of HgCl2 (containing radioactive Hg). Pretreatment with Zn increased mRNA expression of MT and enhanced accumulation of Hg in the renal cortex of male and female rats. In addition, injection with Zn also protected animals from Hg-induced nephrotoxicity. Studies using isolated proximal tubules from rabbit kidney demonstrated that Hg-MT is taken up rapidly at the apical and basolateral membranes. The current findings suggest that at least part of this uptake occurs through an endocytic process. This study is the first to examine the uptake of Hg-MT complexes in isolated proximal tubules. Overall, the findings of this study suggest that supplementation with Zn may be a viable strategy for reducing the risk of Hg intoxication in at-risk populations.
... where: sPi-concentration of serum inorganic phosphate (mmol/L), Ar(P)-atomic weight of phosphorus (30.97 g/mol), BV-average blood volume per 1 kg for rodents (0.06 L) [41], m-rat body weight (g). The levels of urinary albumin were measured by immuno-turbidimetry using reagent kits (Vital, Saint Petersburg, Russia) on an CA-90 analyzer (Furuno, Nagasaki, Japan). ...
Chronic kidney disease—mineral and bone disorder (CKD-MBD) plays a significant role in causing cardiovascular morbidity and mortality related to CKD. CKD-MBD has been studied during advanced stages when changes in inorganic phosphate (Pi) and its hormonal regulation are obvious. The initial phases of myocardial remodeling (MR) in early CKD-MBD remain poorly understood. We induced mild CKD-MBD in spontaneously hypertensive rats using 3/4 nephrectomy. Animals were fed standard chow, containing 0.6% phosphate. In each animal, we analyzed indices of chronic kidney injury, bone turnover and Pi exchange, and assessed the myocardial histology and gene expression profile. Applied CKD-MBD models corresponded to human CKD S1-2 with low bone turnover and without an increase in systemic Pi-regulating factors (parathyroid hormone and fibroblast growth factor 23). In mild CKD-MBD models, we found MR features characterized by cardiomyocyte hypertrophy, interstitial and perivascular fibrosis, intramyocardial artery media thickening, along with alterations in Ppp3ca, Mapk1, Jag1, Hes1, Ptch1, Numb, Lgr4 and Bmp4 genes. Among other genes, the down-regulation of Jag1 was most tightly associated with either myocardial hypertrophy or fibrosis. Myocardial alterations concurrently occurred with mild CKD-MBD and comprised fibrosis preceding cardiomyocyte hypertrophy. The histological features of MR were associated with myocardial P accumulation in settings of low bone turnover, prior to a response of systemic Pi-regulating factors and with alterations in calcineurin, ERK1/2, Notch, BMP and Hedgehog genes.
... The Hct and Hgb levels of both groups were lower after LPS-injection than those at baseline; this finding may be attributed to hemodilution resulting from abundant intravenous infusions. A rat has a circulating blood volume of approximately 5.5%-7% of body weight (Lee and Blaufox, 1985), and in this study, LPS injection and resuscitation fluids were administered according to 3.6% of body weight. This is the reason for lower Hct and Hgb levels after baseline. ...
... S p = 0.2 ml/sec is the pump speed, and BV is the blood volume. Blood volume is estimated based on rat weight according to the established formula: BV [mL] = 0.06 × body weight (g) + 0.77 (mL) [18,36]. The cardiac output (F) and the ICG half-life (τ) were independently calculated (Supplementary Table 1, Supplementary Table 2, and Supplementary Fig. 2). ...
PurposeVascular endothelium plays a central role in the pathogenesis of acute and chronic radiation injuries, yet the mechanisms which promote sustained endothelial dysfunction and contribute to late responding organ failure are unclear. We employed 2nd window (> 1100 nm emission) Near-Infrared (NIR) imaging using indocyanine green (ICG) to track and define the role of the notch ligand Delta-like ligand 4 (Dll4) in mediating vascular injury in two late-responding radiosensitive organs: the lung and kidney.ProceduresConsomic strains of female Salt Sensitive or SS (Dll4-high) and SS with 3rd chromosome inherited from Brown Norway, SS.BN3 (Dll4-low) rats at ages 11–12 weeks were used to demonstrate the impact of reduced Dll4 expression on long-term vascular integrity, renal function, and survival following high-dose 13 Gy partial body irradiation at 42- and 90 days post-radiation. 2nd window dynamic NIR fluorescence imaging with ICG was analyzed with physiology-based pharmacokinetic modeling and confirmed with assays of endothelial Dll4 expression to assess the role of endogenous Dll4 expression on radiation injury protection.ResultsWe show that SS.BN3 (Dll4-low) rats are relatively protected from vascular permeability disruption compared to the SS (Dll4-high) strain. We further demonstrated that SS.BN3 (Dll4-low) rats have reduced radiation induced loss of CD31+ vascular endothelial cells, and increased Dll4 vascular expression is correlated with vascular dysfunction.Conclusions
Together, these data suggest Dll4 plays a key role in pathogenesis of radiation-induced vascular injury to the lung and kidney.
... Implanted osmotic pumps provide continuous release of its contents over the duration of the experiment. Based on pre-exposure body weights and an initial blood volume of 13 mL (Lee & Blaufox, 1985), the rats should have only received 6.25 mg (3.8 mM) of 5-HMF per min compared to an immediate 9 g (5.5 M) with intravenous infusion. Alternatively, the lack of an effect of 5-HMF on SaO 2 may be due to the time and method of blood collection, that is, post-HA during anesthesia. ...
Decreased blood-tissue oxygenation at high altitude (HA) increases mitochondrial oxidant production and reduces exercise capacity. 5-Hydroxymethylfurfural (5-HMF) is an antioxidant that increases hemoglobin's binding affinity for oxygen. For these reasons, we hypothesized that 5-HMF would improve muscle performance in rats exposed to a simulated HA of ~5500 m. A secondary objective was to measure mitochondrial activity and dynamic regulation of fission and fusion because they are linked processes impacted by HA. Fisher 344 rats received 5-HMF (40 mg/kg/day) or vehicle during exposure to sea level or HA for 72 h. Right ankle plantarflexor muscle function was measured pre- and post-exposure. Post-exposure measurements included arterial blood gas and complete blood count, flexor digitorum brevis myofiber superoxide production and mitochondrial membrane potential (ΔΨm), and mitochondrial dynamic regulation in the soleus muscle. HA reduced blood oxygenation, increased superoxide levels and lowered ΔΨm, responses that were accompanied by decreased peak isometric torque and force production at frequencies >75 Hz. 5-HMF increased isometric force production and lowered oxidant production at sea level. In HA exposed animals, 5-HMF prevented a decline in isometric force production at 75-125 Hz, prevented an increase in superoxide levels, further decreased ΔΨm, and increased mitochondrial fusion 2 protein expression. These results suggest that 5-HMF may prevent a decrease in hypoxic force production during submaximal isometric contractions by an antioxidant mechanism.
... The circulating blood volume was calculated using the following formula: blood volume (mL) = 0.06 × body weight (g) + 0.77 [34]. The purified CAF-EVs obtained from in vitro culture conditions were injected intravenously into mice to achieve the indicated CAF-EVs protein concentration in circulation. ...
Background:
Cancer-associated thrombosis (CAT) is the leading cause of morbidity and mortality. Cancer-associated fibroblasts (CAFs) are a prominent component of the tumor microenvironment that contributes to cancer progression through direct cell-cell interactions and the release of extracellular vesicles (EVs). However, the role of CAFs in CAT remains unclear.
Objective:
This study aims to investigate whether CAFs aggravate CAT and the underlying molecular mechanism using a preclinical mouse lung cancer model.
Methods:
We designed a Lewis lung carcinoma (LLC) tumor-bearing mouse model. CAFs were characterized using fluorescence immunohistostaining. The presence of podoplanin, a platelet-activating membrane protein through C-type lectin-like receptor-2 (CLEC-2), in EVs isolated from primary CAFs or LLC tumor tissues was assessed by immunoblotting. The platelet activation and aggregation abilities of the EVs were quantified using flow cytometry. Podoplanin plasma levels were measured by ELISA. Venous thrombosis was induced in the femoral vein using 2.5% ferric chloride. The anti-C type lectin-like receptor 2 (CLEC-2) monoclonal antibody 2A2B10 was used to deplete CLEC-2 on the surface of the platelets.
Results:
CAFs expressing CD90, PDGFRβ, HSP47, CD34, and vimentin, co-expressed podoplanin and induced platelet activation and aggregation in a CLEC-2-dependent manner. Tumor-bearing mice showed elevated podoplanin plasma levels. CAF-EV injection and tumor-bearing mice showed shorter occlusion time in the venous thrombosis model. Although tumor growth was not altered, antibody-induced CLEC-2 depletion suppressed venous thrombosis in the tumor-bearing state but not in the healthy condition.
Conclusions:
CAFs and CAF-derived EVs induce CLEC-2-dependent platelet aggregation and aggravate venous thrombosis.
... The total blood volume (TBV) was calculated according to the following formula: TBV (in milliliters) = weight (in grams)-0.06 (in milligrams per gram) + 0.77 (14). To induce shock, Sprague-Dawley rats were subjected to 50% (7.59-9.99 ...
Objective:
Histone deacetylase inhibitors (HDACIs) have been reported to improve survival in rats with hemorrhagic shock (HS). However, no consensus exists on the most effective HDACIs and their administration routes. We herein aimed to determine the optimal HDACIs and administration route in rats with HS.
Methods:
Survival analysis: In experiment I, male Sprague-Dawley rats were subjected to HS (mean arterial pressure [MAP] was maintained at 30 to 40 mm Hg for 20 min), and intravenously injected with the following agents (n = 8 per group): 1) no treatment, 2) vehicle (VEH), 3) entinostat (MS-275), 4) [N-((6-(Hydroxyamino)-6-oxohexyl)oxy)-3,5-dimethylbenzamide] (LMK-235), 5) tubastatin A, 6) trichostatin A (TSA), and 7) sirtinol. In experiment II, rats were intraperitoneally injected with TSA. Mechanism research: In experiments I and II, rats were observed for 3 h, after which blood samples and liver, heart, and lung tissues were harvested.
Results:
In experiment I, 75% rats in the VEH group but only 25% rats in the LMK-235 and sirtinol groups died within ≤5 h of treatment, whereas the survival of rats in the MS-275, tubastatin A, and TSA groups was significantly prolonged. MS-275, LMK-235, tubastatin A, and TSA significantly reduced histopathological scores, apoptosis cell numbers, and inflammatory cytokine levels. In experiment II, the survival was longer after i.v. TSA treatment than after i.p. TSA treatment, and the IL-6 levels in the heart were significantly lower in rat who received i.p. TSA treatment than in those who received i.v. TSA treatment.
Conclusions:
The i.v. effect was superior to the i.p. effect, while nonselective and isoform-specific classes I and IIb HDACIs had similar effects.
... Body weight (g)+0.77) (Lee and Blaufox, 1985); in a 250 g rat, it would be 15.77 mL. ...
Streptozotocin (STZ) is the most used diabetogenic chemical for creating rat models of type 1 and type 2 diabetes. Despite ~60 years of using STZ in animal diabetes research, some prevailing views about STZ preparation and use are not supported by evidence. Here, we provide practical guides for using STZ to induce diabetes in rats. Susceptibility to the diabetogenic effect of STZ is inversely related to age, and males are more susceptible to STZ than females. Wistar and Sprague-Dawley rats, the most commonly-used rat strains, are sensitive to STZ, but some strains (e.g., Wistar-Kyoto rats) are less sensitive. STZ is mostly injected intravenously or intraperitoneally, but its intravenous injection produces more stable hyperglycemia. Despite the prevailing view, no fasting is necessary before STZ injection, and injection of its anomer-equilibrated solutions (i.e., more than 2 hours of dissolving) is recommended. Mortality following the injection of diabetogenic doses of STZ is due to severe hypoglycemia (during the first 24 h) or severe hyperglycemia (24 h after the injection and onwards). Some measures to prevent hypoglycemia-related mortality in rats include providing access to food soon after the injection, administration of glucose/sucrose solutions during the first 24-48 h after the injection, administration of STZ to fed animals, and using anomer-equilibrated solutions of STZ. Hyperglycemia-related mortality following injection of high doses of STZ can be overcome with insulin administration. In conclusion, STZ is a valuable chemical for inducing diabetes in rats, but some practical guides should be considered to perform well-conducted and ethical studies.
... Indeed, given a kidney-to-body weight ratio of 5.23 mg per g (Zou et al. 1996), we assume a kidney (1988); Zou et al. (1996) fmol/mL Gutkowska et al. (1984) weight W K of 1.49 g. Based on the body weight-to-blood volume relationship from Lee and Blaufox (1985), we assume a circulating blood volume of 17.8 mL. This corresponds to a circulating plasma volume V circ of 10.3 mL, given a hematocrit of 0.42 (Munger and Baylis 1988). ...
The renin-angiotensin system (RAS) plays a pivotal role in the maintenance of volume homeostasis and blood pressure. In addition to the well-studied systemic RAS, local RAS have been documented in various tissues, including the kidney. Given the role of the intrarenal RAS in the pathogenesis of hypertension, a role established via various pharmacologic and genetic studies, substantial efforts have been made to unravel the processes that govern intrarenal RAS activity. In particular, several mechanisms have been proposed to explain the rise in intrarenal angiotensin II (Ang II) that accompanies Ang II infusion, including increased angiotensin type 1 receptor (AT1R)-mediated uptake of Ang II and enhanced intrarenal Ang II production. However, experimentally isolating their contribution to the intrarenal accumulation of Ang II in Ang II–induced hypertension is challenging, given that they are fundamentally connected. Computational modelling is advantageous because the feedback underlying each mechanism can be removed and the effect on intrarenal Ang II can be studied. In this work, the mechanisms governing the intrarenal accumulation of Ang II during Ang II infusion experiments are delineated and the role of the intrarenal RAS in Ang II-induced hypertension is studied. To accomplish this, a compartmental ODE model of the systemic and intrarenal RAS is developed and Ang II infusion experiments are simulated. Simulations indicate that AT1R-mediated uptake of Ang II is the primary mechanism by which Ang II accumulates in the kidney during Ang II infusion. Enhanced local Ang II production is unnecessary. The results demonstrate the role of the intrarenal RAS in the pathogenesis of Ang II-induced hypertension and consequently, clinical hypertension associated with an overactive RAS.
... In skeletal muscle, the interstitial compliance was 13 and 20 mL/kg/mmHg in hypothyroid and euthyroid rats and the corresponding numbers for the back skin are 27 and 50 mL/kg/mmHg [14]. If we set the plasma volume of these rats as 70 mL/kg [15], then we find the value of ξ for the skeletal muscle and back skin is in the range of 1.4 mmHg [=(70 mL/kg)/(50 mL/mmHg/kg)] to 5.4 mmHg [=(70 mL/kg)/(13 mL/kg/mmHg)]. The data analysis of six HD is done with ϕ set as 4 and ξ set as 4 mmHg. ...
Over the course of hemodialysis, fluid and protein are restituted from the tissue compartment to the circulation compartment through the endothelia. Our previous model analysis on fluid and protein transport during hemodialysis is expanded to account for changes occurring in the tissue. The measured initial and end plasma protein concentration (PPC, Cp and Cp’) for six hemodialysis studies are analyzed by this expanded model. The computation results indicate that the total driving pressure to restitute fluid from the tissue to the circulation ranges from 5.4 to 20.3 mmHg. The analysis identifies that the increase in plasma colloidal osmotic pressure (COP) contributes 78 ± 6% of the total driving pressure, the decrease in microvascular blood pressure 32 ± 4%, the increase in the COP of interstitial fluid −6 ± 3%, and the decrease in interstitial fluid pressure −5 ± 2%. Let this ratio (Cp’ − Cp)/Cp’ be termed the PPC increment. The six HDs can be divided into three groups which are to have these PPC increments 25.7%, 14.5 ± 2.6(SD)% and 8.3%. It is calculated that their correspondent filtration coefficients are 0.43, 1.29 ± 0.28 and 5.93 mL/min/mmHg and the relative reductions in plasma volume (RRPV) −22.1%, −13.1 ± 6% and −9.4%. The large variations in PPC increments and RRPV show the filtration coefficient is a key factor to regulate the hemodialysis process.
... The venous cannula was used for drug administration and blood collection, whereas the arterial catheter was used for hemorrhage and hemodynamic monitoring. The estimated total blood volume (ETBV) of the rats was calculated as follows: ETBV (mL) = body weight (g) Â 0.06 (mL/g) + 0.77 (45). The rats were hemorrhaged with 35% of their ETBV over 20 min (17.5% ETBV over 7 min, then 17.5% ETBV over 13 min). ...
Background:
Monocytes and monocyte-derived tissue factor (TF) promote the development of sepsis-induced acute lung injury (ALI). Classical monocytes (C-Mcs) can be induced to express TF. Valproic acid (VPA) alleviates hemorrhagic shock (HS)-induced ALI (HS/ALI) and inhibits TF expression in monocytes. We hypothesized that C-Mcs and C-Mc-derived TF promoted HS/ALI and that VPA could inhibit C-Mc-derived TF expression and attenuate HS/ALI.
Methods:
Wistar rats and THP-1 cells were used to evaluate our hypothesis. Monocyte subtypes were analyzed by flow cytometry, mRNA expression was measured by fluorescence quantitative PCR, protein expression was measured by Western blotting, immunofluorescence or immunohistology, inflammatory cytokines levels were measured by ELISA, and ALI scores were used to determine the degree of ALI.
Results:
The blood %C-Mcs and C-Mcs/non-C-Mcs ratios, monocyte TF levels, serum and/or lung inflammatory cytokine levels, and ALI scores of HS rats were significantly increased (p < 0.05). After monocyte depletion and thrombin inhibition, the inflammatory cytokine levels and ALI scores were significantly decreased (p < 0.05). VPA reduced the %C-Mcs and C-Mcs/non-C-Mcs ratios, TF expression, inflammatory cytokine levels and ALI scores during HS (p < 0.05) and inhibited HS-induced monocyte Egr-1 and p-ERK1/2 expression (p < 0.05). VPA inhibited hypoxia-induced TF expression in THP-1 cells by regulating the p-ERK1/2-Egr-1 axis.
Conclusion:
C-Mcs and C-Mc-derived TF accelerate the development of HS/ALI by increasing thrombin production. VPA inhibits HS-induced C-Mc production of TF by regulating the p-ERK1/2- Egr-1 axis and alleviates HS/ALI.
... The maximum concentration was chosen based off of the initial dilution of degradable NPs into the blood volume of a rat. 42 Following treatment of L929s with various physiologically relevant concentrations of DNPs, we observed no significant decrease in metabolic activity compared to a healthy PBS control (Figure 4D). ...
Nanoparticles that undergo a localized morphology change to target areas of inflammation have been previously developed but are limited by their lack of biodegradability. In this paper, we describe a low ring strain cyclic olefin monomer, 1,3-dimethyl-2-phenoxy-1,3,4,7-tetrahydro-1,3,2-diazaphosphepine 2-oxide (MePTDO), that rapidly polymerizes via ring-opening metathesis polymerization (ROMP) at room temperature to generate well-defined degradable polyphosphoramidates with high monomer conversion (>84%). Efficient MePTDO copolymerizations with norbornene-based monomers are demonstrated, including a norbornenyl monomer functionalized with a peptide substrate for inflammation-associated matrix metalloproteinases (MMPs). The resulting amphiphilic peptide brush copolymers self-assembled in aqueous solution to generate micellar nanoparticles (30 nm in diameter) which exhibit excellent cyto- and hemocompatibility and undergo MMP-induced assembly into micron scale aggregates. As MMPs are upregulated in the heart post-myocardial infarction (MI), the MMP-responsive micelles were applied to target and accumulate in the infarcted heart following intravenous administration in a rat model of MI. These particles displayed a distinct biodistribution and clearance pattern in comparison to non-degradable analogues. Specifically, accumulation at the site of MI, competed with elimination predominantly through the kidney rather than the liver. Together, these results suggest this as a promising new biodegradable platform for inflammation targeted delivery.
... If we account for 74% bioavailability of melatonin after an intraperitoneal injection (Yeleswaram et al., 1997), the resorbed amount of melatonin would then be 1.48 mg. According to the formula BV 0.06 × BM + 0.77, where BV is the total blood volume and the BM is the body mass of a rat (Lee and Blaufox, 1985), the blood volume of a 200 g rat would be 12.77 ml. Thus, the final concentration of the exogenously applied melatonin in a blood volume of 12.77 ml would be 0.11589 mg/ml or 115.89 × 10 6 pg/ml. ...
It has widely been thought that in the process of nerve regeneration Schwann cells populate the injury site with myelinating, non-myelinating, phagocytic, repair, and mesenchyme-like phenotypes. It is now clear that the Schwann cells modify their shape and basal lamina as to accommodate re-growing axons, at the same time clear myelin debris generated upon injury, and regulate expression of extracellular matrix proteins at and around the lesion site. Such a remarkable plasticity may follow an intrinsic functional rhythm or a systemic circadian clock matching the demands of accurate timing and precision of signalling cascades in the regenerating nervous system. Schwann cells react to changes in the external circadian clock clues and to the Zeitgeber hormone melatonin by altering their plasticity. This raises the question of whether melatonin regulates Schwann cell activity during neurorepair and if circadian control and rhythmicity of Schwann cell functions are vital aspects of neuroregeneration. Here, we have focused on different schools of thought and emerging concepts of melatonin-mediated signalling in Schwann cells underlying peripheral nerve regeneration and discuss circadian rhythmicity as a possible component of neurorepair.
... Measured activity from the blood samples was also corrected for the radioactive decay of 89 Zr. Total blood activity was calculated taking into account the theoretical rat blood volume calculated based on body weight using the expression: (Blood volume = 0.06 × Body weight + 0.77 (Lee and Blaufox, 1985)). ...
Adalimumab is an anti-TNFα drug approved for uveitis treatment by subcutaneous injection. This administration route exposes patients to systemic adverse effects and makes difficult to obtain therapeutic drug concentrations in the site of action due to the anatomical and physiological barriers of the eye. These inconveniences could be avoided by intravitreal injection. The aim of this study is to evaluate the pharmacokinetic profile and the biodistribution of the intravitreal administration of ⁸⁹Zr-adalimumab in a uveitis rat model using PET imaging. Adalimumab was radiolabelled to ⁸⁹Zr with a maximum specific activity of 10 MBq/mg. Four μL containing ≃1.74 MBq of ⁸⁹Zr-labelled adalimumab were injected into the vitreous. A microPET acquisition was carried out immediately after the injection and at different time points through a 10-day study and blood samples were obtained through the tail vein. Radiolabelling was successfully performed with a radiochemical purity after ultrafiltration of 99.69%. The antibody ocular pharmacokinetics followed a one-compartment model, showing an intraocular elimination half-life of 9.77 hours for healthy rats and 41.43 hours for rats with uveitis, implying that ⁸⁹Zr-adalimumab remains around four times longer in rats with the disease compared to healthy ones. However, blood concentration half-life had similar values in both groups. In conclusion, this study shows for the first time the ocular and blood pharmacokinetic analysis of adalimumab in a uveitis model in rats.
... Changes in plasma volume were calculated by the Strauss formula (23) = Hb d0 /Hb d2 Â [(100 À Ht d2 )/(100 À Ht d0 ) À 1] Â 100, where Hb is hemoglobin and Ht is hematocrit. The values of the Strauss formula are used as a proxy to assess traditional human and rodent plasma volume measurements with 125 I-labeled human serum albumin (24,25). ...
Loop diuretics are commonly used diuretics in the treatment of fluid retention, but induce hypovolemia-related renal dysfunction. Sodium-glucose cotransporter SGLT2 inhibitors induce osmotic diuresis but body fluid volume is maintained by stimulating vasopressin-induced fluid intake and collecting duct water reabsorption as reported in diabetic rats. We aimed to test the hypothesis that unlike SGLT2 inhibitors, loop diuretics lack activation of similar fluid homeostatic mechanisms. Non-diabetic male Sprague-Dawley rats were treated daily by oral gavage with vehicle, SGLT2 inhibitor ipragliflozin (5mg/kg) or loop diuretic furosemide (50mg/kg) and monitored in metabolic cages for 2 or 7 days. Ipragliflozin and furosemide similarly increased urine volume on day 2. This was associated with increased serum sodium concentration, urine vasopressin excretion, fluid intake, and solute-free water reabsorption in response to ipragliflozin but not to furosemide. Ipragliflozin maintained fluid balance (fluid intake - urine volume) on day 2 and total body water (TBW) measured by bioimpedance spectroscopy and serum creatinine on day 7. In comparison, furosemide decreased fluid balance on day 2, and decreased TBW and increased serum creatinine on day 7. Furosemide, but not ipragliflozin, increased plasma renin activity, and systolic blood pressure was similar among the groups. In conclusion, the osmotic diuresis of the SGLT2 inhibitor increased serum sodium concentration and the vasopressin-related stimulation of fluid intake and renal water retention maintained fluid balance, whereas the loop diuretic did not engage the compensatory vasopressin system. The data suggest differences in vasopressin and fluid homeostatic responses between SGLT2 inhibitors and loop diuretics.
... mL (cisterna magna~0.19 mL) [35][36][37]. With a CSF tracer quantity of 75 μg eventually draining into the systemic blood circulation (assuming complete drainage and without removal from the system), the concentration of tracer in the blood would be about~3.95 ...
Objectives
The current understanding of cerebral waste clearance (CWC) involves cerebrospinal fluid (CSF) participation but lacks convincing evidence for the direct participation of the parenchymal vascular system. The objective of this study was to evaluate the role of the parenchymal vascular system in CSF tracer clearance in rats.Methods
We used superparamagnetic iron oxide–enhanced susceptibility-weighted imaging (SPIO-SWI) and quantitative susceptibility mapping (QSM) methods to simultaneously study 7 T MRI signal changes in parenchymal veins, arteries, and their corresponding para-vascular spaces in 26 rats, following intra-cisterna magna (ICM) infusion of different CSF tracers (FeREX, Ferumoxytol, Fe-Dextran) to determine the amount of tracer in the artery and vein quantitatively.ResultsWe observed that the parenchymal venous system participated in CSF tracer clearance following ICM infusion of different MRI tracers with different concentrations of iron. Parenchymal venous participation was more obvious when 75 μg iron was injected. In the parenchymal veins, the relative mean (± SE) value of the susceptibility increased by 13.5 (± 1.0)% at 15 min post-tracer infusion (p < 0.01), and 33.6 (± 6.7)% at 45 min post-tracer infusion (p = 0.01), compared to baseline. In contrast to the parenchymal veins, a negligible amount of CSF tracer entered the parenchymal arteries: 1.3 (± 2.6)% at 15 min post-tracer infusion (p = 0.6), and 12 (± 19)% at 45 min post-tracer infusion (p = 0.5), compared to baseline.ConclusionsMRI tracers can enter the parenchymal vascular system and more MRI tracers were observed in the cerebral venous than arterial vessels, suggesting the direct participation of parenchymal vascular system in CWC.Key points
• MRI results revealed that the parenchymal venous system directly participates in cerebrospinal fluid tracer clearance following ICM infusion of MRI tracer.
• Different sizes of MRI tracers can enter the parenchymal venous system.
Fluid efflux from the brain plays an important role in solute waste clearance. Current experimental approaches provide little spatial information, and data collection is limited due to short duration or low frequency of sampling. One approach shows tracer efflux to be independent of molecular size, indicating bulk flow, yet also decelerating like simple membrane diffusion. In an apparent contradiction to this report, other studies point to tracer efflux acceleration. We here develop a one-dimensional advection–diffusion model to gain insight into brain efflux principles. The model is characterized by nine physiological constants and three efflux parameters for which we quantify prior uncertainty. Using Bayes’ rule and the two efflux studies, we validate the model and calculate data-informed parameter distributions. The apparent contradictions in the efflux studies are resolved by brain surface boundaries being bottlenecks for efflux. To critically test the model, a custom MRI efflux assay measuring solute dispersion in tissue and release to cerebrospinal fluid was employed. The model passed the test with tissue bulk flow velocities in the range 60 to 190 μ m/h. Dimensional analysis identified three principal determinants of efflux, highlighting brain surfaces as a restricting factor for metabolite solute clearance.
Antibody-based therapeutics (ABTs), including monoclonal/polyclonal antibodies and fragment crystallizable region (Fc)-fusion proteins, are increasingly used in disease treatment, driving the global market growth. Understanding the pharmacokinetic (PK) properties of ABTs is crucial for their clinical effectiveness. This study investigated the PK profile and tissue distribution of efineptakin alfa, a long-acting recombinant human interleukin-7 (rhIL-7-hyFc), using enzyme-linked immunosorbent assay (ELISA) and accelerator mass spectrometry (AMS). Totally, four rats were injected intramuscularly with 1 mg/kg of rhIL-7-hyFc containing 14C-rhIL-7-hyFc, which was prepared via reductive methylation. Serum total radioactivity (TRA) and serum rhIL-7-hyFc concentrations were quantified using AMS and ELISA, respectively. The TRA concentrations in organs were determined by AMS. Serum TRA peaked at 10 hours with a terminal half-life of 40 hours. The rhIL-7-hyFc exhibited a mean peak concentration at around 17 hours and a rapid elimination with a half-life of 12.3 hours. Peak concentration and area under the curve of TRA were higher than those of rhIL-7-hyFc. Tissue distribution analysis showed an elevated TRA concentrations in lymph nodes, kidneys, and spleen, indicating rhIL-7-hyFc’s affinity for these organs. The study also simulated the positions of 14C labeling in rhIL-7-hyFc, identifying specific residues in the fragment of rhIL-7 portion, and provided the explanation of distinct analytes targeted by each method. Combining ELISA and AMS provided advantages by offering sensitivity and specificity for quantification as well as enabling the identification of analyte forms. The integrated use of ELISA and AMS offers valuable insights for the development and optimization of ABT.
Background
The major concern in patients who have suffered from cardiac arrest (CA) and undergone successful extracorporeal cardiopulmonary resuscitation (E‐CPR) is poor neurological outcomes. In this study, we aimed to introduce a rat model of selective brain perfusion (SBP) during E‐CPR to improve the neurological outcome after CA.
Methods
The rats underwent 7 min of untreated asphyxial CA and then were resuscitated with E‐CPR for 30 min. The right external jugular vein and right femoral artery were separately cannulated to the E‐CPR outflow and inflow. The right common carotid artery was cannulated from the proximal to the distal side for SBP. Subsequently, rats were removed from E‐CPR, wounds were closed, and 90 min of intensive care were provided. Neurological deficit scores were tested after 4 h of recovery when the rats were mechanical ventilation‐free. S100 calcium‐binding protein B (S100B) and glial fibrillary acidic protein (GFAP) were detected through immunohistochemistry (IHC) of brain tissue.
Results
The rats that received SBP while resuscitated by E‐CPR showed markedly better neurological performances after 4‐h recovery than those resuscitated by E‐CPR only. The IHC staining of GFAP and S100B in the hippocampus was low in the rats receiving SBP during E‐CPR, but only GFAP showed significant differences.
Conclusions
We successfully developed a novel and reproducible rat model of SBP while resuscitated by E‐CPR to ameliorate the neurological performances after CA. This achievement might have opportunities for studying how to improve the neurological outcome in the clinical condition.
We present one plant that has promising anti-anemic properties in developing countries.
Pre-hospital potentially preventable trauma related deaths are mainly due to hypoperfusion-induced tissue hypoxia leading to irreversible organ dysfunction at or near the point of injury or during transportation prior to receiving definitive therapy. The prolyl hydroxylase domain (PHD) is an oxygen sensor that regulates tissue adaptation to hypoxia by stabilizing hypoxia inducible factor (HIF). The benefit of PHD inhibitors (PHDi) in the treatment of anemia and lactatemia arises from HIF stabilization, which stimulates endogenous production of erythropoietin and activates lactate recycling through gluconeogenesis. The results of this study provide insight into the therapeutic roles of MK-8617, a pan-inhibitor of PHD-1, 2, and 3, in the mitigation of lactatemia in anesthetized rats with polytrauma and hemorrhagic shock. Additionally, in an anesthetized rat model of lethal decompensated hemorrhagic shock, acute administration of MK-8617 significantly improves one-hour survival and maintains survival at least until 4 h following limited resuscitation with whole blood (20% EBV) at one hour after hemorrhage. This study suggests that pharmaceutical interventions to inhibit prolyl hydroxylase activity can be used as a potential pre-hospital countermeasure for trauma and hemorrhage at or near the point of injury.
Antibiotic resistance still represents a global health concern which diminishes the pool of effective antibiotics. With the vancomycin derivative FU002, we recently reported a highly potent substance active against Gram-positive bacteria with the potential to overcome vancomycin resistance. However, the translation of its excellent antimicrobial activity into clinical efficiency could be hampered by its rapid elimination from the blood stream. To improve its pharmacokinetics, we encapsulated FU002 in PEGylated liposomes. For PEG-liposomal FU002, no relevant cytotoxicity on liver, kidney and red blood cells was observed. Studies in Wistar rats revealed a significantly prolonged blood circulation of the liposomal antibiotic. In microdilution assays it could be demonstrated that encapsulation does not diminish the antimicrobial activity against staphylococci and enterococci. Highlighting its great potency, liposomal FU002 exhibited a superior therapeutic efficacy when compared to the free form in a Galleria mellonella larvae infection model.
Platelet transfusions are essential for managing bleeding and hemostatic dysfunction and could be expanded as a cell therapy due to the multifunctional role of platelets in various diseases. Creating these cell therapies will require modifying transfusable donor platelets to express therapeutic proteins. However, there are currently no appropriate methods for genetically modifying platelets collected from blood donors. Here, we describe an approach using platelet-optimized lipid nanoparticles containing mRNA (mRNA-LNP) to enable exogenous protein expression in human and rat platelets. Within the library of mRNA-LNP tested, exogenous protein expression did not require nor correlate with platelet activation. Transfected platelets retained hemostatic function and accumulated in regions of vascular damage after transfusion into rats with hemorrhagic shock. We expect this technology will expand the therapeutic potential of platelets.
Trauma and hemorrhagic shock-associated pre-hospital deaths are mainly due to hypoperfusion-induced tissue hypoxia leading to irreversible organ dysfunction at or near the point of injury or during transportation prior to receiving definitive therapy. The prolyl hydroxylase domain (PHD) is an oxygen sensor that regulates tissue adaptation to hypoxia by stabilizing hypoxia inducible factor (HIF). The benefit of PHD inhibitors (PHDi) in the treatment of anemia and lactatemia arises from HIF stabilization, which stimulates endogenous production of erythropoietin and activates lactate recycling through gluconeogenesis. The results of this study provide insight into the therapeutic roles of MK-8617, a pan-inhibitor of PHD-1, 2, and 3, in the mitigation of lactatemia in anesthetized rats with polytrauma and hemorrhagic shock. Additionally, in an anesthetized rat model of lethal decompensated hemorrhagic shock (65% of estimated blood volume (EBV)), acute administration of MK-8617 significantly improves one-hour survival and maintains survival at least until 4 hours following limited resuscitation with whole blood (20% EBV) at one hour after hemorrhage. This study suggests that pharmaceutical interventions to inhibit prolyl hydroxylase activity can be used as a potential pre-hospital countermeasure for trauma and hemorrhage at or near the point of injury.
Herein, we have developed a drug-loaded matrix metalloproteinase (MMP)-responsive micellar nanoparticle (NP) intended for minimally invasive intravenous injection during the acute phase of myocardial infarction (MI) and prolonged retention in the heart for small-molecule drug delivery. Peptide-polymer amphiphiles (PPAs) bearing a small-molecule MMP inhibitor (MMPi), PD166793, were synthesized via ring-opening metathesis polymerization (ROMP) and formulated into spherical micelles by transitioning to aqueous solution. The resulting micellar NPs underwent MMP-induced aggregation, demonstrating enzyme responsiveness. Using a rat MI model, we observed that these NPs were capable of successfully extravasating into the infarcted region of the heart where they were retained due to the active, enzyme-mediated targeting, remaining detectable after 1 week post administration without increasing macrophage recruitment. Furthermore, in vitro studies show that these NPs demonstrated successful drug release following MMP treatment and maintained drug bioactivity as evidenced by comparable MMP inhibition to free MMPi. This work establishes a targeted NP platform for delivering small-molecule therapeutics to the heart after MI, opening possibilities for myocardial infarction treatment.
Background: Anaemia is a very serious condition in Zambia. One of the plants that has been used traditionally is Phyllanthus muellerianus where different parts of shrub are used to treat a number of diseases in Zambian folklore medicine. Earlier studies have investigated medicinal properties of its aqueous root extracts. This study evaluated the effect of P. muellerianus roots on the haematological indices of albino rats and determined its phytochemical profile. In order to prove this, we carried out phytochemical screening of the root extract and assessed the anti-anaemic effect of the aqueous extract on laboratory rats with tail-bled induced anaemia. Materials and Methods: Thirty-six male albino rats placed in six groups were used for the study. The groups comprised the 100, 200, and 400 mg/kg plant extract, Ranferon (200 mg/kg positive control), anaemic (non-treated control) and a normal (non-anaemic control) groups. Anaemia, induced through bleeding of the rats, was defined as haemoglobin (Hb) levels less than 12 g/dL. The anti-anaemic potential of the plant was determined by comparing its effect on the haematological parameters of rats on treatment to that of the control group. Results: Phytochemical screening revealed positive results for alkaloids, flavonoids, saponins, glycosides, steroids, triterpenoids and tannins with varying amounts. After treatment, rats on the 400 mg/kg plant extract dose showed the greatest increase in the mean values for Hb, Packed cell volume (PCV) and RBC count were 43.31.2%, 15.40.3 g/dL and 6.30.3 x106 /L respectively, when compared to the negative control group (P < 0.05). Conclusions: The aqueous root extract of P. muellerianus was efficacious against anaemia in a dose-dependent manner. The phytochemical compositions seem to be responsible for its haematopoietic properties. Thus, the root decoction of P. muellerianus is useful in alleviating anaemia and the results lend credence to its use in traditional medicine in the management of anaemia.
Hypothesis:
Liposomes coated with long polysarcosine (PSar) chains at a high density might enable long blood circulation and attenuate accelerated blood clearance (ABC) phenomenon.
Experiments:
In this study, we controlled the length (23, 45, 68 mers) and density (5, 10, 15 mol%) of PSar on liposomal coatings and, furthermore, investigated the effects of PSar length and density on the blood circulation time, biodistribution, immune response, and ABC phenomenon induction. Length-controlled PSar-bound lipids (PSar-PEs) were synthesized using a click reaction and inserted into bare liposomes at different combinations of chain lengths and proportions.
Findings:
Although all PSar-coated liposomes (PSar-lipos) had similar morphological, physical, and chemical properties, they had different blood circulation times and biodistribution, and exerted varied effects on the immune system. All PSar-lipos with different PSar length and density showed a similar anti-PSar IgM response. Liposomes modified with the longest PSar chain (68 mers) at a high density (15 mol%) showed the longest blood circulation time and, additionally, attenuated ABC phenomenon compared with PEG-lipo. The ex vivo analysis of the biodistribution of liposomes revealed that a thick PSar layer enhanced the blood circulation time of liposomes due to the reduction of the accumulation of liposomes in the liver and spleen. These findings provide new insights into the relationship between IgM expression and ABC phenomenon inhibition.
Calcium plays a vital role in various biological processes, including muscle contractions, blood clotting, skeletal mineralization, and cell signaling. While extracellular calcium makes up less than 1% of total body calcium, it is tightly regulated since too high or too low extracellular calcium concentration can have dangerous effects on the body. Mathematical modeling is a well-suited approach to investigate the complex physiological processes involved in calcium regulation. While mathematical models have been developed to study calcium homeostasis in male rats, none have been used to investigate known sex differences in hormone levels nor the unique physiological states of pregnancy and lactation. Calcitriol, the active form of vitamin D, plays a key role in intestinal calcium absorption, renal calcium reabsorption, and bone remodeling. It has been shown that when compared to age-matched male rats, females have significantly lower calcitriol levels. In this study we first seek to investigate the impact of this difference as well as other known sex differences on calcium homeostasis using mathematical modelling. Female bodies differ from male bodies in that during their lifetime they may undergo massive adaptations during pregnancy and lactation. Indeed, maternal adaptations impact calcium regulation in all mammals. In pregnant rodents, intestinal absorption of calcium is massively increased in the mother's body to meet the needs of the developing fetus. In a lactating rodent, much of the calcium needs of milk are met by bone resorption, intestinal absorption, and renal calcium reabsorption. Given these observations, the goal of this project is to develop multi-scale whole-body models of calcium homeostasis that represents (1) how sex differences impact calcium homeostasis in female vs. male rats and (2) how a female body adapts to support the excess demands brought on by pregnancy and lactation. We used these models to quantify the impact of individual sex differences as well as maternal adaptations during pregnancy and lactation. Additionally, we conducted "what if" simulations to test whether sex differences in calcium regulation may enable females to better undergo maternal adaptations required in pregnancy and lactation than males.
Background:
Early detection and quantification of perioperative hemorrhage remains challenging. Peripheral intravenous waveform analysis (PIVA) is a novel method that uses a standard intravenous catheter to detect interval hemorrhage. We hypothesize that subclinical blood loss of 2% of the estimated blood volume (EBV) in a rat model of hemorrhage is associated with significant changes in PIVA. Secondarily, we will compare PIVA association with volume loss to other static, invasive, and dynamic markers.
Methods:
Eleven male Sprague Dawley rats were anesthetized and mechanically ventilated. A total of 20% of the EBV was removed over ten 5 minute-intervals. The peripheral intravenous pressure waveform was continuously transduced via a 22-G angiocatheter in the saphenous vein and analyzed using MATLAB. Mean arterial pressure (MAP) and central venous pressure (CVP) were continuously monitored. Cardiac output (CO), right ventricular diameter (RVd), and left ventricular end-diastolic area (LVEDA) were evaluated via transthoracic echocardiogram using the short axis left ventricular view. Dynamic markers such as pulse pressure variation (PPV) were calculated from the arterial waveform. The primary outcome was change in the first fundamental frequency (F1) of the venous waveform, which was assessed using analysis of variance (ANOVA). Mean F1 at each blood loss interval was compared to the mean at the subsequent interval. Additionally, the strength of the association between blood loss and F1 and each other marker was quantified using the marginal R2 in a linear mixed-effects model.
Results:
PIVA derived mean F1 decreased significantly after hemorrhage of only 2% of the EBV, from 0.17 to 0.11 mm Hg, P = .001, 95% confidence interval (CI) of difference in means 0.02 to 0.10, and decreased significantly from the prior hemorrhage interval at 4%, 6%, 8%, 10%, and 12%. Log F1 demonstrated a marginal R2 value of 0.57 (95% CI 0.40-0.73), followed by PPV 0.41 (0.28-0.56) and CO 0.39 (0.26-0.58). MAP, LVEDA, and systolic pressure variation displayed R2 values of 0.31, and the remaining predictors had R2 values ≤0.2. The difference in log F1 R2 was not significant when compared to PPV 0.16 (95% CI -0.07 to 0.38), CO 0.18 (-0.06 to 0.04), or MAP 0.25 (-0.01 to 0.49) but was significant for the remaining markers.
Conclusions:
The mean F1 amplitude of PIVA was significantly associated with subclinical blood loss and most strongly associated with blood volume among the markers considered. This study demonstrates feasibility of a minimally invasive, low-cost method for monitoring perioperative blood loss.
Carbonized nanogels (CNGs) are carbon-based nanomaterials possessing excellent antibacterial and antiviral activities for treating infectious diseases. Thus, investigations of the biodistribution of CNGs are crucial in ensuring their biosafety for in vivo applications. In this study, we combined a labeling scheme, employing tetrachloropalladate (PdCl42-) ions to selectively label the administered CNGs in solubilized tissue samples, and an automatic sample pretreatment scheme, using a knotted reactor to effectively separate the PdCl42--labeled CNGs from the free PdCl42- ions and the tissue matrices, to enable reliable and interference-free quantification of CNGs through measuring the signal intensities of Pd using inductively coupled plasma mass spectrometry (ICP-MS). After optimizing the labeling conditions and the separation scheme, we observed that the PdCl42- ions bound strongly to the CNGs (dissociation constant: 23.0 nM), with the method's detection limits reaching 1.6 fg L-1 and 0.9 μg L-1 within working ranges from 10-4 to 1 μg L-1 and from 1 to 1000 μg L-1, respectively. We verified the reliability and applicability of this analytical method through spike analyses of solubilized rat liver, spleen, kidney, lung, brain, and blood samples (recoveries ranging from 96 to 102%) and through analyses of these rat organ and tissue samples after giving rats an intravenous dose of CNGs (2.5 mg kg-1 body weight). The biodistribution data indicated that these administered CNGs deposited mainly in the liver, lung, and spleen at 10 min and 1 h post-administration. Our study revealed that this post-administration labeling scheme coupled with ICP-MS allows accurate determination of the biodistribution of carbonized nanomaterials.
Gadoxetate, a magnetic resonance imaging (MRI) contrast agent, is a substrate of organic-anion-transporting polypeptide 1B1 and multidrug resistance-associated protein 2. Six drugs, with varying degrees of transporter inhibition, were used to assess gadoxetate dynamic contrast enhanced MRI biomarkers for transporter inhibition in rats. Prospective prediction of changes in gadoxetate systemic and liver AUC (AUCR), resulting from transporter modulation, were performed by physiologically-based pharmacokinetic (PBPK) modelling. A tracer-kinetic model was used to estimate rate constants for hepatic uptake (khe), and biliary excretion (kbh). The observed median fold-decreases in gadoxetate liver AUC were 3.8- and 1.5-fold for ciclosporin and rifampicin, respectively. Ketoconazole unexpectedly decreased systemic and liver gadoxetate AUCs; the remaining drugs investigated (asunaprevir, bosentan, and pioglitazone) caused marginal changes. Ciclosporin decreased gadoxetate khe and kbh by 3.78 and 0.09 mL/min/mL, while decreases for rifampicin were 7.20 and 0.07 mL/min/mL, respectively. The relative decrease in khe (e.g., 96% for ciclosporin) was similar to PBPK-predicted inhibition of uptake (97–98%). PBPK modelling correctly predicted changes in gadoxetate systemic AUCR, whereas underprediction of decreases in liver AUCs was evident. The current study illustrates the modelling framework and integration of liver imaging data, PBPK, and tracer-kinetic models for prospective quantification of hepatic transporter-mediated DDI in humans.
Objective
Shock heart syndrome (SHS) is associated with lethal arrhythmias (ventricular tachycardia/ventricular fibrillation, VT/VF). We investigated whether liposome-encapsulated human hemoglobin vesicles (HbVs) has comparable persistent efficacy to washed red blood cells (wRBCs) for improving arrhythmogenesis in the subacute to chronic phase of SHS.Methods
Optical mapping analysis (OMP), electrophysiological study (EPS), and pathological examinations were performed on blood samples from Sprague-Dawley rats following induction of hemorrhagic shock. After hemorrhagic shock, the rats were immediately resuscitated by transfusing 5% albumin (ALB), HbV, or wRBCs. All rats survived for 1 week. OMP and EPS were performed on Langendorff-perfused hearts. Spontaneous arrhythmias and heart rate variability (HRV) were evaluated using awake 24-h telemetry, cardiac function by echocardiography, and pathological examination of Connexin43.ResultsOMP showed significantly impaired action potential duration dispersion (APDd) in the left ventricle (LV) in the ALB group whereas APDd was substantially preserved in the HbV and wRBCs groups. Sustained VT/VF was easily provoked by EPS in the ALB group. No VT/VF was induced in the HbV and wRBCs groups. HRV, spontaneous arrhythmias, and cardiac function were preserved in the HbV and wRBCs groups. Pathology showed myocardial cell damage and Connexin43 degradation in the ALB group, all of which were attenuated in the HbV and wRBCs groups.ConclusionLV remodeling after hemorrhagic shock caused VT/VF in the presence of impaired APDd. Similar to wRBCs, HbV persistently prevented VT/VF by inhibiting persistent electrical remodeling, preserving myocardial structures, and ameliorating arrhythmogenic modifying factors in the subacute to chronic phase of hemorrhagic shock-induced SHS.
Background:
Onchocerciasis (river blindness) caused by the filarial worm Onchocerca volvulus is a neglected tropical disease that affects the skin and eyes of humans. Mass drug administration with ivermectin (IVM) to control the disease often suffers from severe adverse events in individuals co-injected with high loads of Loa loa microfilariae (mf). Thus loiasis animal models for counter-screening of compounds effective against onchocerciasis are needed, as are the corresponding onchocerciasis screening models. The repertoire of such models is highly limiting. Therefore, this study was aimed at developing and validating mf immunocompetent small animal models to increase tools for onchocerciasis drug discovery.
Methodology/principal findings:
O. ochengi mf from cattle skin and L. loa mf from human blood were used to infect BALB/c mice and Mongolian gerbils, and IVM was used for model validation. O. ochengi mf were given subcutaneously to both rodents while L. loa mf were administered intravenously to mice and intraperitoneally to gerbils. IVM was given orally. In an 8-day model of O. ochengi mf in BALB/c mice, treatment with IVM depleted all mf in the mice, unlike the controls. Also, in a 2.5-day model of L. loa mf in BALB/c, IVM significantly reduced mf in treated mice compared to the untreated. Furthermore, the gerbils were very susceptible to O. ochengi mf and IVM eradicated all mf in the treated animals. In the peritoneal L. loa mf gerbil model, IVM reduced mf motility in treated animals compared to the controls. In a 30-day gerbil co-injection model, IVM treatment cleared all O. ochengi mf and reduced motility of L. loa mf. Both mf survived for up to 50 days in a gerbil co-injection model.
Conclusions/significance:
We have developed two immunocompetent small animal models for onchocerciasis and loiasis that can be used for microfilaricide discovery and to counter-screen onchocerciasis macrofilarides.
Isotopic assays of brain glucose utilization rates have been used for more than four decades to establish relationships between energetics, functional activity, and neurotransmitter cycling. Limitations of these methods include the relatively long time (1–60 min) for the determination of labeled metabolite levels and the lack of cellular resolution. Identification and quantification of fuels for neurons and astrocytes that support activation and higher brain functions are a major, unresolved issues. Glycolysis is preferentially up‐regulated during activation even though oxygen level and supply are adequate, causing lactate concentrations to quickly rise during alerting, sensory processing, cognitive tasks, and memory consolidation. However, the fate of lactate (rapid release from brain or cell–cell shuttling coupled with local oxidation) is long disputed. Genetically encoded biosensors can determine intracellular metabolite concentrations and report real‐time lactate level responses to sensory, behavioral, and biochemical challenges at the cellular level. Kinetics and time courses of cellular lactate concentration changes are informative, but accurate biosensor calibration is required for quantitative comparisons of lactate levels in astrocytes and neurons. An in vivo calibration procedure for the Laconic lactate biosensor involves intracellular lactate depletion by intravenous pyruvate‐mediated trans‐acceleration of lactate efflux followed by sensor saturation by intravenous infusion of high doses of lactate plus ammonium chloride. In the present paper, the validity of this procedure is questioned because rapid lactate–pyruvate interconversion in blood, preferential neuronal oxidation of both monocarboxylates, on‐going glycolytic metabolism, and cellular volumes were not taken into account. Calibration pitfalls for the Laconic lactate biosensor also apply to other metabolite biosensors that are standardized in vivo by infusion of substrates that can be metabolized in peripheral tissues. We discuss how technical shortcomings negate the conclusion that Laconic sensor calibrations support the existence of an in vivo astrocyte–neuron lactate concentration gradient linked to lactate shuttling from astrocytes to neurons to fuel neuronal activity. image
Ethnopharmacological relevance
Anemia is a very serious condition in Zambia. One of the plants that has been used traditionally is Phyllanthus muellerianus where different parts of shrub are used to treat a number of diseases in Zambian folklore medicine. Earlier studies have investigated medicinal properties of its aqueous root extracts. This study evaluated the effect of P. muellerianus roots on the hematological indices of albino rats and determined its phytochemical profile.
Aim of the study
To carry out phytochemical screening of the root extract and assess the ant-anemic effect of the aqueous extract on laboratory rats with tail-bled induced anemia
Materials and Methods
Thirty-six male albino rats placed in six groups were used for the study. The groups comprised the 100, 200, and 400 mg/kg plant extract, Ranferon (200 mg/kg) positive control, anemic non treated control and a normal (non-anemic) control. Anemia, induced through bleeding of the rats, was defined as hemoglobin (Hb) levels less than 12 g/dL. The anti-anemic potential of the plant was determined by comparing its effect on the hematological parameters of rats on treatment to that of the control group.
Results
After treatment, rats on the 400 mg/kg plant extract dose showed the greatest increase in the mean values for Hb, Packed cell volume (PCV) and RBC count were 43.3±1.2%, 15.4±0.3 g/dL and 6.3±0.3 x10⁶ /mL respectively, when compared to the negative control group (P < 0.05). Phytochemical screening revealed positive results for alkaloids, flavonoids, saponins, glycosides, steroids, triterpenoids and tannins with varying amounts.
Conclusions.
The aqueous root extract of P. muellerianus was efficacious against anemia in a dose-dependent manner. The phytochemical compositions seem to be responsible for its hematopoietic properties. Thus, the root decoction of P. muellerianus is useful in alleviating anemia and the results lend credence to its use in traditional medicine in the management of anemia.
Pain management plays an essential role in medical care. Previous studies showed that pain is a dynamic process involving multiple mechanisms, which inspired the concept of multimodal analgesia. Therefore, a drug delivery system loaded with a single analgesic may be insufficient for pain control. In this study, an implantable thermogel/electrospun fiber (Gel/Fiber) system loaded with bupivacaine hydrochloride (BUP-HCl) and acetaminophen (APAP) was synthesized. In the composite, BUP-HCl was preferentially released from the hydrophilic thermogel to relieve nociceptive pain, followed by the release of APAP in a more sustained manner form hydrophobic fibers to reduce the inflammatory reaction. Pain behavioral study and activation assay of spinal glial cells in the chronic constriction injury (CCI) model demonstrated the superior analgesic efficacy and chronic pain prevention property of the Gel/Fiber system.
Furthermore, the composite exhibited satisfactory biocompatibility, as shown by histological and pharmacokinetic analysis. These results indicate that the successful sequential BUP-HCl/APAP release by a Gel/Fiber system alleviates chronic pain with good biocompatibility. Our study may pave the way for the future application of extended-delivery systems.
The use of many benzodiazepines is controlled worldwide due to their high likelihood of abuse and potential adverse effects. Flubromazepam—a designer benzodiazepine—is a long-acting gamma-aminobutyric acid subtype A receptor agonist. There is currently a lack of scientific evidence regarding the potential for flubromazepam dependence or other adverse effects. This study aimed to evaluate the dependence potential, and cardiotoxicity via confirmation of the QT and RR intervals which are the factors on the electrical properties of the heart of flubromazepam in rodents. Using a conditioned place preference test, we discovered that mice treated intraperitoneally with flubromazepam (0.1 mg/kg) exhibited a significant preference for the flubromazepam-paired compartment, suggesting a potential for flubromazepam dependence. In addition, we observed several cardiotoxic effects of flubromazepam; 100-μM flubromazepam reduced cell viability, increased RR intervals but not QT intervals in the electrocardiography measurements, and considerably inhibited potassium channels in a human ether-à-go-go-related gene assay. Collectively, these findings suggest that flubromazepam may have adverse effects on psychological and cardiovascular health, laying the foundation for further efforts to list flubromazepam as a controlled substance at both national and international levels.
Negatively charged microspheres (NCMs) are postulated as a new form of treatment for chronic wounds. Despite the efficacy shown at clinical level, more studies are required to demonstrate their safety and local effect. The objective of the work was to confirm the lack of NCM systemic absorption performing a biodistribution study of the NCMs in an open wound rat animal model. To this end, radiolabeling of NCMs with technetium-99m was optimized and biodistribution studies were performed by in vivo SPEC/CT imaging and ex vivo counting during 24 h after topical administration. The studies were performed on animals treated with a single or repeated dose to study the effect of macrophages during a prolonged treatment. NCM radiolabeling was achieved in a simple, efficient and stable manner with high yield. SPECT/CT images showed that almost all NCMs (about 85 %) remained on the wound for 24 h either after single or multiple administrations. Ex vivo biodistribution studies confirmed that there was no accumulation of NCMs in any organ or tissue except in the wound area, suggesting a lack of absorption. In conclusion, NCMs can be considered safe as local wound treatment since they remain at the administration area.
Surgical preparation of rats for micropuncture resulted in a marked decrease in sodium excretion (UNaV) compared to awake animals. Associated with surgery, hematocrit (Hct) rose. Studies were performed to determine whether the rise in Hct resulted from reduced plasma volume (PV) or increased red cell volume (RCV) and to explore the relation of such alterations to the fall in UNaV. PV and RCV were determined in the calm awake rat using 125I-albumin and 51Cr-labeled red blood cells. Micropuncture surgery was performed and RCV, PV, and Hct again measured. After anesthesia and femoral artery catheterization, Hct was not different from Hct in awake animals (42.9 +/- 2.8%). The Hct increased following surgery to 48.2 +/- 2.8% (P less than 0.001), accompanied by a large fall in PV (-18.9 +/- 2.3%, P less than 0.001) with no change in RCV. Plasma volume repletion to awake values restored UNaV toward levels appropriate for dietary intake in animals on a high salt diet. Althouth plasma repletion slightly increased UNaV above awake values in low salt diet rats, they continued to avidly retain salt with respect to total salt load.
A standard method is described which gives reproducible blood volume values for rats and their various organs and tissues.
A method for simultaneous estimation of plasma volume, red cell volume and thiocyanate space in unanesthetized rats utilizing a polyethylene catheter in the common carotid artery with T-1824, P ³² -tagged red cells, and NaSCN was perfected and determinations were performed on 77 male albino rats. Determinations of plasma volume using T-1824 or I ¹³¹ -serum albumin in the same animal gave essentially identical results. Total blood volume was calculated as the sum of P ³² -red cell volume and T-1824-plasma volume and was found to be 5.75 ml/100 gm body weight in normal rats and 5.61 ml/100 gm in splenectomized rats. There was a wide variation in the F cell values of normal rats but little in splenectomized rats. This difference was highly significant and was attributed to the presence of the spleen. The average thiocyanate space was found to be 33.0 ml and 35.8 ml/100 gm in normal and splenectomized rats, respectively.
A method is described for the catheterization of the carotid of the rat which permits blood volume determinations to be made on unanesthetized animals. The cell volume (P ³² ) and plasma volume (T-1824) were measured simultaneously on the day after catheterization. The average F cells factor was 0.739 (S.D., 0.053) in 11 normal rats and 0.726 (S.D., 0.041) in 10 splenectomized rats. In 50 unanesthetized normal rats the plasma volume averaged 3.90 ml/100 gm body weight. The blood and cell volumes calculated by using the F cells factor of 0.74 and the separately determined plasma trapping' factor of 0.95 averaged 5.93 ml/ 100 gm and 2.14 ml/100 gm, respectively. These values agree closely with those determined from the simultaneous measurement of cell and plasma volumes and also with the values obtained on 27 normal rats under ether.
A micro-method of blood volume determination using commercially available I131-human serum albumin has been described. From a single sample of 25 μl of blood withdrawn from a peripheral site, it is possible to obtain total blood volume, plasma volume and hematocrit in not more than 15 minutes. Normal values are presented for these parameters in the mouse, hamster, rat, guinea pig and rabbit. The normal value for total blood volume by this method was 7.0 to 8.3 ml/100 g of body weight in the rat, hamster, guinea pig and rabbit. A value of 13.3 ml/100 g of body weight was found for the mouse. The plasma volume for all the animal species tested was 3.9 to 5.0 ml/100 g of body weight, with the exception of the mouse. The plasma volume found in the mouse was 8.8 ml/100 g of body weight. There was good agreement of these results when compared to the macro-method which requires a minimum of 2 ml of blood.
1. The mean blood and packed cell volumes of 22 adult male rats, as measured by transfused tagged cells, was found to be 4.95 and 2.32 ml per 100 g of body weight respectively.
1. A method for the determination of blood volume of the rat by radioisotope dilution is described. 2. In 34 normal adult white rats, average blood volume was 6.3% of body weight, with a stand, dev. of 0.7. 3. In 7 rats, the determination was repeated with a maximum error of ±1% body weight. 4. These results are in agreement with those reported in the literature using different methods.
1. The blood volume of normal rats determined by the use of Fe59 labeled red blood cells is essentially the same as with P32 labeled cells.
Determinations of blood and plasma volume partitions in the growing rat
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Metboff i, Favour CB: Determinations of blood and
plasma volume partitions in the growing rat. Am J
Physiol 141:695â€"706, 1944
Changesin blood,plasmaand redcellvolume in the male rat, as a function of age
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GarciaiF: Changesin blood,plasmaand redcellvolume
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19â€"24, 1957
A method for determining bloodvolumein rats
- Griffith Iq
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Griffith iQ, Campbell R: A method for determining
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Intercellular plasma of centni fuged human erythrocytes as measured by means of iodo'31-albumin BetcherEH, HarnissEB: Studiesof plasmavolume,red cell volume and total blood volume in young growing rats
- Ca Owen
- Power
Owen CA, Power MH: Intercellular plasma of centni fuged human erythrocytes as measured by means of iodo'31-albumin. J ApplPhysiol 5:323-329, 1953 19. BetcherEH, HarnissEB: Studiesof plasmavolume,red cell volume and total blood volume in young growing rats. JPhysiol 139:64â€"78, 1957 76 Lee and Blaufox The Journal of Nuclear Medicine
Distribution ofceltsand plasmain the normaland splenectomized dog and its influencein bloodvolumeestimateswith P32and 1-1824
- Eb Reeve
- Mi Gregersen
- Th Allen
Reeve EB, Gregersen MI, Allen TH, et at: Distribution
ofceltsand plasmain the normaland splenectomized dog
and its influencein bloodvolumeestimateswith P32and
1-1824. Am J Physiol 175:195†" 203, 1953
Studiesof plasmavolume,red cell volume and total blood volume in young growing rats
- Harnisseb Betchereh
BetcherEH, HarnissEB: Studiesof plasmavolume,red
cell volume and total blood volume in young growing rats.
JPhysiol 139:64â€"78, 1957