Tyrosinemia type 1 in pediatric nephrology: Not always straightforward

The main clinical features of tyrosinemia type 1 usually appear in the first months of life, including fever, diarrhea, vomiting, liver involvement, growth failure, and renal proximal tubulopathy with subsequent hypophosphatemic rickets. An early diagnosis is crucial in order to provide specific management and to prevent complications. Here, we report on two cases referred primarily to pediatric nephrologists for the diagnosis of “neonatal tubulopathy” and management of “X-linked hypophosphatemia (XLH),” respectively. Our aim is to emphasize that (1) even a mixed tubulopathy can reveal tyrosinemia, and (2) tyrosinemia is a classic differential diagnosis of XLH that should not be forgotten, especially in the era of the anti-FGF23 burosumab.     

Role of retinol in protecting epithelial cell damage induced by Clostridium difficile toxin A

Vitamin A (retinol), a fat-soluble vitamin, is an essential nutrient for the normal functioning of the visual system, epithelial cell integrity and growth, immunity, and reproduction. Our group has investigated the effect of high doses of oral vitamin A on early childhood diarrhea in our prospective community-based studies from Northeast Brazil and found a beneficial role in reducing the mean duration but not incidence of diarrheal episodes. In this study, we explored the role of retinol supplementation in intestinal cell lines following Clostridium difficile toxin A (TxA) challenge. C. difficile is the most common anaerobic pathogen borne with antibiotic-borne diarrhea and pseudomembranous colitis. Since retinol is critical for the integrity of tight junctions and to modulate the cell cycle, we have focused on changes in transepithelial electrical resistance (TEER) in Caco-2, a more differentiated intestinal cell line, and on models of cell proliferation, migration and viability in IEC-6 cells, an undifferentiated crypt cell line, following TxA injury. In this model, retinol therapy reduced apoptosis, improved cell migration and proliferation, and prevented the reduction in TEER, following C. difficile TxA challenge in a glutamine-free medium. These results suggest the role of retinol in protecting intestinal epithelial barrier function from C. difficile TxA enterotoxic damage.     

Labially displaced ectopically erupting maxillary permanent canine: interceptive treatment and long-term results.

This case report demonstrates how extracting a maxillary deciduous canine affects the eruption path of a labially displaced ectopically erupting permanent canine. A long-term follow-up is presented, and the biologic mechanisms are discussed.     

Evolution with age of the acetylcholinesterase activity in rectal suction biopsy in Hirschsprung's disease

The acetylcholinesterase (AChE) activity in Hirschsprung's disease was analyzed for histochemical patterns according to age. Its evolutional nature was also assessed. Two hundred thirty children (0 to 16 years of age) with acute or chronic obstipation were submitted to rectal suction biopsy for AChE histochemical staining. One hundred nineteen of them showed abnormal AChE activity. Retrospective analysis of those cases permitted us to establish three histochemical patterns: Pattern I, thick nerve trunks present only in the submucosa and, characteristically, absence of AChE activity in the lamina propria. This pattern was predominant in newborn up to 3 months of age and was designated the newborn pattern. Pattern II, thin nerve fibers in the muscularis mucosae and submucosa with a clear infiltration in the lamina propria. This pattern was mainly seen in children older than 1 year of age and was called classical pattern. Pattern III, an intermediate pattern showing morphologic characteristics of the two previous patterns with predominance of one or another, according to the age. A prospective study was also made in 15 children with Hirschsprung's disease who were submitted to suction rectal biopsies at different ages. In this study, a clear evolutional character of the AChE activity was observed from the newborn pattern to the intermediate and finally to the classical pattern.     

Evaluation of the clinical, hemodynamic and neurohormonal response to levosimendan administration in decompensated heart failure patients. One-month follow-up.

INTRODUCTION: Levosimendan is an inodilatory drug with hemodynamic effects in patients with decompensated chronic heart failure. AIM: Short-term (one month) evaluation of clinical, hemodynamic and neurohormonal changes in patients with decompensated chronic heart failure undergoing levosimendan therapy. METHODS: Twenty-six (21 male) consecutive patients were studied, corresponding to 32 levosimendan administrations (bolus + 24h infusion), aged 56.7+/-13.0 years, with decompensated chronic heart failure, in NYHA functional class III-IV (78.1% in class IV), and cardiac index (CI) <2.5 l/min/m2. Clinical (NYHA class), non-invasive hemodynamic (echocardiography) and neurohormonal (Elecsys ECLIA NT-ProBNP) evaluations were performed before levosimendan administration and on days 1, 4, 10 and 30. RESULTS: 1) Until day 10, there was a progressive decrease in NT-ProBNP values and weight (p<0.001), with an increase in CI (p<0.001); 2) NYHA functional class improved progressively, with 76% of the patients in NYHA class II at day 30; 3) NT-ProBNP values at day 1 correlated inversely (r=-0.414; p=0.024) with CI at day 4; and 4) the absolute decrease in NT-ProBNP values at day 4 (relative to baseline values) correlated with weight loss at day 4 (r=0.495, p=0.005), day 10 (r=0.424, p=0.031) and day 30 (r=0.486, p=0.030). CONCLUSION: Levosimendan therapy in patients with decompensated chronic heart failure contributes to progressive NYHA class improvement. The variations seen in NYHA class and hemodynamics was reflected in changes in NT-ProBNP.     

p53 expression in Barrett's oesophagus,dysplasia, and adenocarcinoma using antibody DO-7

Barrett's oesophagus has a well-recognized association with oesophageal adenocarcinoma, with phenotypic progression through dysplasia to malignancy. The nuclear phosphoprotein p53 is a putative tumour suppressor with mutations resulting in both loss of negative growth regulatory function and possible gain of oncogene function. Many mutant forms have a prolonged half-life and are demonstrable with immunohistochemical techniques. We examined 62 endoscopic oesophageal biopsies and 36 oesophageal resections for p53 overexpression using the monoclonal antibody DO-7 on paraffin-embedded tissue. The series included 40 cases of Barrett's metaplasia, 13 cases of dysplasia, and 81 cases of adenocarcinoma. None of the cases of metaplasia was p53-positive, compared with 4/13 cases of dysplasia and 52/81 cases of adenocarcinoma. There was no association between the degree of dysplasia and p53 expression, although a trend emerged of increasing p53 expression with higher tumour grade. We conclude that p53 overexpression is frequent in oesophageal adenocarcinoma and may be related to tumour grade. p53 overexpression is not restricted to neoplastic lesions and mutation of this tumour suppressor may occur early in the malignant progression of Barrett's oesophagus.     

Leptospiral antigens in the liver of experimentally infected guinea pig and their relation to the morphogenesis of liver damage.

In order to investigate the morphogenes of experimental leptospirosis by morphologic and immunohistologic methods, 24 guinea-pigs were inoculated intraperitoneally with L. interrogans serogroup Icterohaemorrhagiae. They were divided in 6 groups, sacrificed from the 1st to the 6th day of infection. Semiquantitative analyses of histopathological liver lesions were performed in 1 micron sections of tissue embedded in glycol-methacrylate. The distribution of leptospiral antigen (L. Ag) and its glycolipoprotein (GLP) was demonstrated by peroxidase-antiperoxidase on paraffin embedded tissue. Significant lesions appeared at the 4th day of infection, progressing to a peak on the 6th day. Inflammation was associated with injury of the portal triad. Liver cells showed either swelling or acidophilic degeneration and necrosis, together with loss of cell cohesion, leading to disarray of liver cell plates. Mitochondria were found progressively enlarged and irregularly distributed. L. Ag expression was parallel to the morphological changes. Portal distribution was significant at the 4th day and on later stages centrilobular localization became predominant. Spiral forms suggestive of intact leptospires were initially found but, chiefly at the 6th day, L. Ag was seen in granules, probably resulting from phagocytosis. GLP staining was similar to granular L. Ag in morphology, and distribution. Cytokeratin condensation was seen in liver cells with acidophilic necrosis and was marked in areas of disorganization of cell plates. Our findings lead us to hypothesize a direct leptospiral cytotoxic effect on endothelial and on liver-cell membranes. At first, leptospires themselves would induce subcellular changes acting mainly on membrane permeability. Afterwards, their granular forms, including GLP, would act as adjuvant factors. These findings demonstrate that the disarray of liver cell plates at the late phase of the disease is genuine.