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Since the first description of a creatine deficiency syndrome, the guanidinoacetate methyltransferase (GAMT) deficiency, in 1994, the two further suspected creatine deficiency syndromes--the creatine transporter (CrT1) defect and the arginine:glycine amidinotransferase (AGAT) deficiency were disclosed. GAMT and AGAT deficiency have autosomal-recessive traits, whereas the CrT1 defect is a X-linked disorder. All patients reveal developmental delay/regression, mental retardation, and severe disturbance of their expressive and cognitive speech. The common feature of all creatine deficiency syndromes is the severe depletion of creatine/phosphocreatine in the brain. Only the GAMT deficiency is in addition characterized by accumulation of guanidinoacetic acid in brain and body fluids. Guanidinoacetic acid seems to be responsible for intractable seizures and the movement disorder, both exclusively found in GAMT deficiency. Treatment with oral creatine supplementation is in part successful in GAMT and AGAT deficiency, whereas in CrT1 defect it is not able to replenish creatine in the brain. Treatment of combined arginine restriction and ornithine substitution in GAMT deficiency is capable to decrease guanidinoacetic acid permanently and improves the clinical outcome. The lack of the creatine/phosphocreatine signal in the patient's brain by means of in vivo proton magnetic resonance spectroscopy is the common finding and the diagnostic clue in all three diseases. In AGAT deficiency guanidinoacetic acid is decreased, whereas creatine in blood was found to be normal. On the other hand the CrT1 defect is characterized by an increased concentration of creatine in blood and urine whereas guanidinoacetic acid concentration is normal. The increasing number of patients detected very recently suffering from a creatine deficiency syndrome and the unfavorable outcome highlights the need of further attempts in early recognition of affected individuals and in optimizing its treatment. The study of creatine deficiency syndromes and their comparative consideration contributes to the better understanding of the pathophysiological role of creatine and other guanidino compounds in man
Previous studies of hypothermia as a treatment for neonatal hypoxic-ischemic encephalopathy (HIE) have yielded mixed results. The present investigators compared the efficacy and safety of hypothermia compared with normothermia in randomized and quasi-randomized trials that were assessed independently by 2 reviewers, with discrepancies resolved by a third. Eight studies of acceptable quality were chosen based on concealment of allocation, method of randomization, masking of outcome assessment, and completeness of follow-up. The risk of both death and moderate to severe neurodevelopmental disability was significantly reduced in infants treated by hypothermia compared to control infants for whom normothermia was maintained. The relative risk was 0.76, with a 95% confidence interval of 0.65–0.88. Hypothermia-treated infants had significantly lower rates of severe neurodevelopmental disability and severe cerebral palsy, and less often had low scores on a Mental Developmental Index and Psychomotor Developmental Index. More control infants died after withdrawal of life support. Cardiac arrhythmias and thrombocytopenia were more common in neonates treated with hypothermia, but were not clinically threatening. The investigators recommend hypothermia for treating postintrapartum asphyxial HIE within 6 hours after birth—especially in neonates with moderate encephalopathy. Continued follow-up of surviving infants is vital in order to identify the long-term effects of hypothermia.
Fifteen patients with cardiac failure (New York Heart Association [NYHA] classes II and III) caused by ischemic heart disease or idiopathic dilatative cardiomyopathy were treated with intravenous administration of creatine phosphate in a dose of 4 gm in the morning followed by 2 gm in the evening, for five days. We evaluated mono- and bidimensional echocardiography before treatment, in the acute phase (at the end of and 30 minutes after the infusion of the first 4-gm dose), and at the fifth day of therapy. Creatine phosphate was administered together with conventional therapy for heart failure, such as digitalis, diuretics, and vasodilators, with a constant dosage of these drugs maintained. The results of the acute and short-term phases show a significant increase of ejection fraction and fractional shortening. The velocity of circumferential shortening also significantly increased in the acute phase, while stroke volume increased only in the second acute evaluation. The clinical conditions and subjective symptoms of the patients improved and five patients moved to a lower NYHA class. Finally, creatine phosphate was able to increase cardiac function indices and improve clinical conditions of patients with chronic heart failure even in association with conventional therapy, without causing side effects.
This review covers mechanisms of action, efficacy, side effects, and toxicity of various classes of antidepressants:tricyclic antidepressants, monoamine oxidase inhibitors, second-generation antidepressants including the selective inhibitors of serotonin reuptake, and novel drugs such as mirtazapine, nefazodone, and venlafaxine. (J Clin Psychopharmacol 1997;17[suppl 1]:2S-18S).
Ferreira GK, Rezin GT, Cardoso MR, Gonçalves CL, Borges LS, Vieira JS, Gomes LM, Zugno AI, Quevedo J, Streck EL. Brain energy metabolism is increased by chronic administration of bupropion.
Objectives: Based on the hypothesis that energy impairment may be involved in the pathophysiology of depression, we evaluated the activities of citrate synthase, malate dehydrogenase, succinate dehydrogenase (SDH), mitochondrial respiratory chain complexes I, II, II-III, IV and creatine kinase (CK) in the brain of rats submitted to chronic administration of bupropion.
Methods: Animals received daily administration of bupropion dissolved in saline (10 mg/kg, intraperitoneal) at 1.0 ml/kg body weight. The rats received injections once a day for 14 days; control rats received an equivalent volume of saline. Twelve hours after the last administration, the rats were killed by decapitation and brain was rapidly removed and kept on an ice plate. The activities of the enzymes were measured in different brain areas.
Results: We observed that the activities of citrate synthase and malate dehydrogenase, mithocondrial respiratory chain complexes I, II-III and IV and CK were not altered after chronic administration of bupropion. However, SDH activity was increased in the prefrontal cortex and cerebellum. In the hippocampus, cerebellum and striatum the activity of complex II was increased after chronic administration of bupropion.
Conclusions: Our results demonstrated that bupropion increased some enzymes of brain energy metabolism. These findings are in accordance with other studies which showed that some antidepressants may improve energy metabolism. The present results reinforce the hypothesis that antidepressants modulate brain energy metabolism.
Creatine has become a popular nutritional supplement among athletes. Recent research has also suggested that there may be a number of potential therapeutic uses of creatine. This paper reviews the available research that has examined the potential ergogenic value of creatine supplementation on exercise performance and training adaptations. Review of the literature indicates that over 500 research studies have evaluated the effects of creatine supplementation on muscle physiology and/or exercise capacity in healthy, trained, and various diseased populations. Short-term creatine supplementation (e.g. 20 g/day for 5–7 days) has typically been reported to increase total creatine content by 10–30% and phosphocreatine stores by 10–40%. Of the approximately 300 studies that have evaluated the potential ergogenic value of creatine supplementation, about 70% of these studies report statistically significant results while remaining studies generally report non-significant gains in performance. No study reports a statistically significant ergolytic effect. For example, short-term creatine supplementation has been reported to improve maximal power/strength (5–15%), work performed during sets of maximal effort muscle contractions (5–15%), single-effort sprint performance (1–5%), and work performed during repetitive sprint performance (5–15%). Moreover, creatine supplementation during training has been reported to promote significantly greater gains in strength, fat free mass, and performance primarily of high intensity exercise tasks. Although not all studies report significant results, the preponderance of scientific evidence indicates that creatine supplementation appears to be a generally effective nutritional ergogenic aid for a variety of exercise tasks in a number of athletic and clinical populations.