Potentiation of benzoate toxicity by glyoxylate. Inhibition of pyruvate carboxylase and the urea cycle

It has been proposed that administration of non-nitrogenous precursors to glycine is necessary to realize the full potential of benzoate metabolism as a pathway for disposal of waste nitrogen during ammonia intoxication (Coude et al., Clin Chim Acta 136: 211-217, 1984). However, when glyoxylate, a keto acid precursor to glycine, was administered with benzoate 1 hr prior to a challenge of ammonia, protection against ammonia toxicity was less successful than with benzoate alone. At the cellular and subcellular levels, glyoxylate and benzoate each inhibited the urea cycle in isolated hepatocytes and pyruvate carboxylase in isolated mitochondria. The action of each drug was associated with depletion of aspartate content in isolated hepatocytes and reduction of pyruvate-dependent incorporation of CO2 into aspartate in assays with isolated mitochondria. Depression of aspartate regeneration by inhibition of pyruvate carboxylase is a likely mechanism for impairment of urea cycle activity by both drugs. In whole animals, inhibition of pyruvate carboxylase may contribute to benzoate toxicity and the adverse influence of glyoxylate on benzoate therapy.     

Comparative efficacy of Hanifin and Rajka''s criteria and the UK working party''s diagnostic criteria in diagnosis of atopic dermatitis in a hospital setting in North India

BACKGROUND: Diagnosis of atopic dermatitis (AD) depends on clinical features because no definitive diagnostic test exists. Criteria proposed by Hanifin and Rajka (Acta Derm Venereol (Stockh) 1980; Suppl 92: 44-47) were acceptable for hospital-based studies but were found not to be suitable for field studies. A UK working party formulated clinical diagnostic criteria that could be used in both hospital and epidemiological settings. Validation studies of the criteria showed widely variable results, probably due to different clinical settings and ethnicity. AIM AND OBJECTIVE: This study was undertaken to validate Hanifin and Rajka's criteria and to assess the comparative efficacy of their criteria and the UK working party's diagnostic criteria in the diagnosis of AD in a hospital setting in North India. SUBJECTS AND METHODS: This study serially included 101 patients with AD and 48 controls of paediatric age group. The study period was from July 2003 to December 2004. RESULTS: Hanifin and Rajka's criteria (sensitivity 96%, specificity 93.75%, positive predictive value 97% (PPV) and negative predictive value (NPV) 91.84%) had a statistical advantage over the UK working party's diagnostic criteria (sensitivity 86%, specificity 95.83%, PPV 97.75% and NPV 76.67%), with a P-value < 0.005.     

Effects of age and age-related hearing loss on the neural representation of speech cues.

OBJECTIVE: To examine the effects of aging and age-related hearing loss on the perception and neural representation of a time-varying speech cue. METHODS: P1, N1 and P2 cortical responses were recorded from younger and older normal-hearing adults, as well as older adults with age-related hearing loss. Synthetic speech tokens representing 10 ms increments along a /ba/-/pa/ voice-onset-time (VOT) continuum were used to evoke the responses. Each participant's ability to discriminate the speech tokens was also assessed. RESULTS: Compared with younger participants, older adults with and without hearing loss had more difficulty discriminating 10 ms VOT contrasts. In addition, both older groups elicited abnormal neural response patterns. There were no significant age-related findings for P1 latency; however, N1 latencies were prolonged for both older groups in response to stimuli with increased VOT durations. Also, P2 latencies were delayed for both older groups. The presence of age-related hearing loss resulted in a significant increase in N1 amplitude in response to voiceless stimuli. CONCLUSIONS: Aging and age-related hearing loss alter temporal response properties in the central auditory system. Because both older groups had difficulty discriminating these same speech stimuli, we conclude that some of the perceptual difficulties described by older adults might be due to age-related changes regulating excitatory and inhibitory processes. SIGNIFICANCE: Some of the speech understanding difficulties expressed by elderly adults may be related to impaired temporal precision in the aging auditory system. This might explain why older adults frequently complain that wearing a hearing aid makes speech louder, but does not necessarily improve their ability to understand speech.     

A midface swelling in a child – A possible diagnostic dilemma

A lump on the midface of a child can pose as a diagnostic dilemma. There is a wide variety of possible differential diagnoses, ranging from simple benign conditions such as a sebaceous cyst, dermoid cyst, lipoma, neuroma and neurofibroma, to potentially devastating conditions such as odontogenic myxoma.A case of a child in which the formulation of a definite diagnosis was clinically and histologically challenging is presented.     

Contribution of glucose tolerance and plasma insulin levels to the relationships between body fat distribution and plasma lipoprotein levels in women.

Numerous interrelated metabolic and morphological variables such as plasma insulin levels, glucose tolerance and abdominal obesity are associated with changes in plasma lipoprotein levels. The present study was undertaken to differentiate, using a multivariate approach, the respective contributions of plasma glucose and insulin levels, obesity and regional adipose tissue distribution to the variance in plasma lipoproteins. The study group was composed of 69 healthy premenopausal women (age 35.4 +/- 5.0 years (mean +/- s.d.); percent body fat 40.7 +/- 10.1). Indices of carbohydrate metabolism showed significant univariate correlations with triglyceride (TG) and/or cholesterol (CHOL) content of plasma VLDL, LDL and HDL (P less than 0.05). Multivariate analyses indicated that the explained variance in plasma VLDL-TG (R2 x 100 = 44 percent, P less than 0.05) and LDL-apoprotein (apo) B levels (R2 x 100 = 33.1 percent, P less than 0.08) was entirely accounted for by indices of carbohydrate metabolism and body fat distribution, whereas total body fatness added no significant contribution to these models. Multivariate analyses also revealed that the best possible regression model to predict the variation in plasma HDL2-CHOL levels only included computed tomography-derived deep abdominal adipose tissue area (P less than 0.0001). All other variables were unable to further improve the explained variance in plasma HDL2-CHOL levels. In partial correlation analyses, indices of carbohydrate metabolism and the waist-to-hip circumference ratio (WHR) remained significantly correlated with plasma VLDL-TG and LDL-apo B levels after adjustment of VLDL-TG and LDL-apo B for either insulin and glucose levels, or for the WHR (P less than 0.08). After correcting for deep abdominal fat accumulation, no significant correlation was observed between indices of carbohydrate metabolism and plasma HDL2-CHOL levels whereas deep abdominal fat showed significant correlations with HDL2-CHOL levels (P less than 0.05) after correction for indices of carbohydrate metabolism. These results suggest that both disturbances in glucose-insulin homeostasis and abdominal obesity are significantly associated with changes in plasma VLDL-TG and LDL-apo B levels and that these associations are partly independent from each other. These results also indicate that mechanisms other than disturbances in glucose homeostasis and hyperinsulinemia are responsible for the association between the level of deep abdominal fat and plasma HDL2-CHOL levels.