Disruption of redox homeostasis and brain damage caused in vivo by methylmalonic acid and ammonia in cerebral cortex and striatum of developing rats.

Hyperammonemia is a common finding in children with methylmalonic acidemia and propionic acidemia, but its contribution to the development of the neurological symptoms in the affected patients is poorly known. Considering that methylmalonic acid (MMA) and propionic acid (PA) predominantly accumulate in these disorders, we investigated the effects of hyperammonemia induced by urease treatment in 30-day-old rats receiving an intracerebroventricular (ICV) injection of MMA or PA on important parameters of redox homeostasis in cerebral cortex and striatum. We evaluated glutathione (GSH) concentrations, sulfhydryl content, nitrate and nitrite concentrations, 2',7'-dichlorofluorescein (DCFH) oxidation, and the activity of antioxidant enzymes. MMA decreased GSH concentrations and sulfhydryl content and increased nitrate and nitrite concentrations in cerebral cortex and striatum from hyperammonemic rats, whereas MMA or ammonia per se did not alter these parameters. MMA plus hyperammonemia also decreased glutathione reductase activity in rat cerebral cortex, but did not affect catalase, superoxide dismutase and glutathione peroxidase activities, neither DCFH oxidation. Furthermore, ICV PA administration alone or combined with hyperammonemia did not alter any of the evaluated parameters. We also found that pre-treatment with antioxidants prevented GSH reduction and sulfhydryl oxidation, whereas N(ω)-nitro-L-arginine methyl ester (L-NAME) prevented the increased nitrate and nitrite concentrations provoked by MMA plus ammonia treatments. Histological alterations, including vacuolization, ischemic neurons, and pericellular edema, were observed in brain of hyperammonemic rats injected with MMA. The data indicate a synergistic effect of MMA and ammonia disturbing redox homeostasis and causing morphological brain abnormalities in rat brain.

Prevalence of malocclusion in primary dentition in a population-based sample of Brazilian preschool children.

AIM: The purpose of the present study was to assess the prevalence of malocclusion in the primary dentition in a randomised representative sample of Brazilian preschool children. MATERIALS AND METHODS: A cross-sectional survey was carried out in Belo Horizonte, Brazil, involving 1069 male and female preschool children from 60 to 71 months of age, randomly selected from public and private preschools and daycare centers. A questionnaire addressing demographic data was sent to parents/guardians in order to characterise the sample. The oral examination of the children was performed by a single, previously calibrated dentist (kappa inter-examiner agreement value = 0.82). The criterion for the categorisation of malocclusion was at least one of the following conditions: posterior crossbite, overjet (> 2 mm), anterior crossbite, anterior open bite and deep overbite. Univariate analysis was performed using the SPSS software RESULTS: The prevalence of malocclusion was 46.2%. Deep overbite was the most prevalent alteration (19.7% of the sample). Posterior crossbite was diagnosed in 13.1% of the children; 10.5% had accentuated overjet; 7.9% had anterior open bite; and 6.7% had anterior crossbite. CONCLUSION: Malocclusion in primary dentition is becoming a significant problem. The prevalence in the present study was high, especially vertical and transversal malocclusions.

Predisposing factors for traumatic dental injuries in Brazilian preschool children.

AIM: The aim of the present study was to assess the prevalence of traumatic dental injury (TDI) in primary teeth and determine predisposing factors. MATERIALS AND METHODS: A cross-sectional study was carried out on 388 male and female Brazilian preschool children between 60 and 71 months of age. A questionnaire addressing demographic data and history of TDI was sent to parents/caregivers. Socioeconomic status was determined using the Social Vulnerability Index (SVI), family income, number of people in the household and parents/caregivers' schooling. The chi-square test was used for the statistical analysis. RESULTS: The prevalence of TDI was 62.1%; 61.7% of the teeth were affected by enamel fracture. Statistically significant associations were found between TDI and increased overjet [OR = 2.24, 95% CI = 1.11- 4.55] and anterior crossbite [OR = 0.38, 95% CI=0.17-0.87]. No statistically significant associations were found between TDI and number of people in the household, family income, social vulnerability, parents/caregivers' schooling, lip competence, overbite, anterior open bite and dental caries (p>0.05). CONCLUSION: The prevalence of TDI was high and enamel fracture was the most common sign of TDI. Children with an increased overjet suffer more TDIs. Socioeconomic factors had no influence over the prevalence of TDI.

Betaterapia no Brasil: perfil de prática

Betaterapia é uma modalidade terapêutica no arsenal de possibilidades da radioterapia em doenças benignas. Entretanto, pouco se conhece de sua prátic no Brasil. .

Establishment of primary care centre for University Malaysia Sabah.

University Malaysia Sabah campus moved to its present site in Kota Kinabalu, Sabah, Malaysia in 1999. A health centre was included in the development plans and a two-storey building was constructed to provide the facility for in-patient and out-patient care. Clinical catchments include 10,000 students, 1000 academic and support staff. The medical faculty was inaugurated in 2003, and it was given the responsibility to establish and run the facility for students and staff of the University. This paper describes the development of the facility from merely a physical structure to what is now a comprehensive, functional outpatient service catering for student healthcare, screening, preventive medicine and health promotional activities. Currently, these services are provided by the faculty members of the Medical School. The incorporation of the medical student teaching and collaborative research adds intangible value to the facility. Future plans for expansion include specialist medical services.

Creatine prevents behavioral alterations caused by methylmalonic acid administration into the hippocampus of rats in the open field task.

Although a variable degree of psychomotor delay/mental retardation is found in a considerable number of patients affected by methylmalonic acidemia, the mechanisms underlying the neuropathology of this disorder are still poorly defined. The present study investigated the effect of acute intrahippocampal administration of methylmalonic acid (MMA), the biochemical hallmark of this disease, on rat behavior in the open field task. Cannulated 60-day-old male Wistar rats received bilateral intrahippocampal injection of MMA (0.1-1.0 micromol) 10 min before training. Controls received 0.1-1.0 micromol NaCl. Testing session was performed 24 h later. We observed that rats administered with 1.0 micromol MMA, but not with lower doses, did not habituate in the open field task, reflecting a deficit of performance. Motor activity, assessed by the number of crossing responses, was the same at training for the groups infused with MMA or NaCl. The effect of MK-801 (15 nmol) and succinate (1.5 micromol) administered 30 min before MMA injection, and of creatine (50 mg/kg, i.p.) administered twice a day for 3 days on the behavioral alterations provoked by MMA in the open field task revealed that only the energetic substrate creatine prevented these effects, reflecting a possible compromise of brain energy production by MMA. The results indicate that high intrahippocampal concentrations of the major metabolite accumulating in methylmalonic acidemia compromises brain functioning, causing deficit of performance in the open field task that may be related to the psychomotor delay/mental retardation observed in the affected patients.