GAMT deficiency: features, treatment, and outcome in an inborn error of creatine synthesis.

BACKGROUND: Guanidinoactetate methyltransferase (GAMT) deficiency is an autosomal recessive disorder of creatine synthesis. The authors analyzed clinical, biochemical, and molecular findings in 27 patients. METHODS: The authors collected data from questionnaires and literature reports. A score including degree of intellectual disability, epileptic seizures, and movement disorder was developed and used to classify clinical phenotype as severe, moderate, or mild. Score and biochemical data were assessed before and during treatment with oral creatine substitution alone or with additional dietary arginine restriction and ornithine supplementation. RESULTS: Intellectual disability, epileptic seizures, guanidinoacetate accumulation in body fluids, and deficiency of brain creatine were common in all 27 patients. Twelve patients had severe, 12 patients had moderate, and three patients had mild clinical phenotype. Twenty-one of 27 (78%) patients had severe intellectual disability (estimated IQ 20 to 34). There was no obvious correlation between severity of the clinical phenotype, guanidinoacetate accumulation in body fluids, and GAMT mutations. Treatment resulted in almost normalized cerebral creatine levels, reduced guanidinoacetate accumulation, and in improvement of epilepsy and movement disorder, whereas the degree of intellectual disability remained unchanged. CONCLUSION: Guanidinoactetate methyltransferase deficiency should be considered in patients with unexplained intellectual disability, and urinary guanidinoacetate should be determined as an initial diagnostic approach.

Performance of broiler chickens supplemented with Bacillus coagulans as probiotic.

1. A newly isolated Bacillus coagulans strain as probiotic was assayed as the only dietary additive for chickens. 2. Chickens receiving no additive at all or only virginiamycin were used for comparison. 3. Two trials each carried out on 75 chickens showed that, in terms of efficacy in growth and food conversion ratio, the B. coagulans biomass as a probiotic had a growth-promoting, prophylactic effect comparable to that of virginiamycin.

Effects on intestinal microflora, gastrointestinal tolerability and antiinflammatory efficacy of diclofenac and nitrofenac in adjuvant arthritic rats.

Since it is known that nitric oxide plays an important protective role in maintaining the tissue integrity and is cytotoxic for invasive micro-organisms, diclofenac and a new original diclofenac-derivate, nitrofenac (containing the nitric oxide group), was administered at doses of 0.3 and 3 mg kg-1 per os to adjuvant arthritic rats. At the 14th, 21st and 28th days after arthritis induction, the antiinflammatory efficacy and the effects on intestinal microflora of the two drugs were evaluated; moreover, at the end of the study period, the gastrointestinal tract was examined macroscopically for any presence of lesions. Daily oral administration of diclofenac and nitrofenac at 3 mg kg-1 markedly and significantly inhibited arthritis development until the end of the study period. Some significant changes were observed in anaerobic and Gram-negative bacterial flora, particularly the total disappearance, in all treated rats, of Escherichia coli 1, also 7 days after the last drug administration. Finally, no ulcers or severe damage were observed macroscopically with either drug, even if some alterations in the mucosa and haemorrhagic effusions were more evident in rats treated with diclofenac at 3 mg kg-1. In conclusion, in this chronic model a similar therapeutic efficacy of diclofenac and nitrofenac is shown in arthritic rats. The better gastrointestinal tolerability observed in nitrofenac-treated rats could be attributed to the release of nitric oxide.