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- Primary distal renal tubular acidosis in children in the South of Tunisia: Study of 15 cases. [Journal Article]
- Tunis Med 2013 Apr; 91(4):258-62.
Background:primary distal renal tubular acidosis in children (RTA) is characterized by metabolic acidosis due to defect in urinary excretion of hydrogen (H+) in the distal tubular. aim: To report the epidemiological, clinical, therapeutic and evolutionary of distal RTA in our patients. Patients and methods: We conducted a retrospective study of all cases of distal RTA collected in the department of pediatrics of Hedi Chaker University hospital in the south of Tunisia, during a period of 23 years (1988-2010). We studied the epidemiological, clinical, biological, evolutionary and therapeutic data. results: During the study period 15 cases of distal RTA were collected. The average age was 6 months (1 month -2 years). Most common presenting symptoms were vomiting (8cases), failure to thrive (4cases), lack of appetite, polyuria-polydipsia syndrome (1case) and urinary infection (2cases). The clinical examination showed staturoponderal delay (9 cases), dehydration (6 cases), signs of rickets (3 cases) and polyuria (10 cases). Biological data showed high urine pH in the presence of metabolic acidosis in 11 cases, hypokalaemia in 10 cases and hypercalciuria in all cases. Urine acidification test with ammonium chloride was performed in 4 cases, the urinary pH was always higher than 5.5 in all cases. Ammoniuria performed in 9 cases was less than 40mmol/l. Radiological investigation objectified a nephrocalcinosis in fourteen patients and signs of rickets in three cases. Deafness was found in three patients. Genetic study performed in two cases showed mutation of ATP6V1B1 gene. The medical treatment involved an alkali load. Long-term outcome was favorable in 7 cases.
Conclusion:The distal renal tubular acidosis is a rare pathology in our country but probably under diagnosed. The clinical gravity of this disease and the risk of evolution towards the terminal renal insufficiency justify an antenatal diagnosis to establish a neonatal management or propose a therapeutic interruption of the pregnancy if the distal RTA is associated with a severe pathology.
- [The research applications of db/db mouse]. [English Abstract, Journal Article]
- Sheng Li Ke Xue Jin Zhan 2013 Feb; 44(1):12-8.
The db/db mice are perfect animal models of type 2 diabetes which have been widely used. The phenotypes of severe obesity, hyperphagia, polydipsia, and polyuria are due to a spontaneous mutation of the leptin receptor (Lepr). The course of the disease is markedly influenced by genetic background, which is more serious in the C57BLKS/J background. And there are many other spontaneous mutations in different sites of Lepr, which produce a series of animal models of obesity, including db(3J)/ db(3J) mice, db(5j)/db(5J) mice, db(pas)/db(pas) mice, Zucker fa/fa rats, and Koletsky fa(k)/fa(k) rats, etc. These rodents appear similar hyperphagia and severe obesity, but different levels of blood glucose, kidney damage and reproductive ability, providing profuse material to investigate the complex function of Lepr. Here we review the history of the discovery of the leptin signaling pathway, the abnormal phenotypes of db/db mice in metabolic, reproductive, immune, etc. Discuss their research applications, reproductive strategy, genotyping guideline, the phenotypic diversity of those animal models with Lepr spontaneous mutation and their mutation patterns, respectively.
- Pathological polydipsia from a brain lesion. [Letter]
- Intern Med J 2013 May; 43(5):604.
- Role of nitric oxide in the pathogenesis of alloxan diabetes. [Journal Article]
- Bull Exp Biol Med 2013 Feb; 154(5):602-5.
We studied the effects of N(w)-nitro-L-arginine (L-NNA), a nonselective inhibitor of NO synthases, on the severity of type 1 diabetes mellitus induced by subcutaneous injection of 130 mg/kg alloxan in August rats with high activity of NO system and in Wistar rats. Five days after alloxan injection, hyperglycemia levels after overnight fasting in August and Wistar rats were 27.1±3.7 and 22.0±1.1 mmol/liter, respectively (p<0.03). The mortality over 15 days after alloxan injection in August rats was higher than in Wistar rats (36 and 26%, respectively). L-NNA normalized glucose levels in diabetics of both groups. It completely prevented mortality in August and reduced it to 13% in Wistar rats. Body weight loss and polydipsia after L-NNA injection were also less pronounced in August rats. Plasma nitrite/nitrate concentrations in August rats were 32% higher than in Wistar rats, both in intact and diabetic rats. These data attest to an important role of NO in the pathogenesis of alloxan diabetes.
- Chronic Kidney Disease in Dogs in UK Veterinary Practices: Prevalence, Risk Factors, and Survival. [JOURNAL ARTICLE]
- J Vet Intern Med 2013 May 6.
BACKGROUND:The prevalence for chronic kidney disease (CKD) in dogs varies widely (0.05-3.74%). Identified risk factors include advancing age, specific breeds, small body size, and periodontal disease. HYPOTHESIS/
OBJECTIVES:To estimate the prevalence and identify risk factors associated with CKD diagnosis and survival in dogs. Purebred dogs were hypothesized to have higher CKD risk and poorer survival characteristics than crossbred dogs.
ANIMALS:A merged clinical database of 107,214 dogs attending 89 UK veterinary practices over a 2-year period (January 2010-December 2011).
METHODS:A longitudinal study design estimated the apparent prevalence (AP) whereas the true prevalence (TP) was estimated using Bayesian analysis. A nested case-control study design evaluated risk factors. Survival analysis used the Kaplan-Meier survival curve method and multivariable Cox proportional hazards regression modeling.
RESULTS:The CKD AP was 0.21% (95% CI: 0.19-0.24%) and TP was 0.37% (95% posterior credibility interval 0.02-1.44%). Significant risk factors included increasing age, being insured, and certain breeds (Cocker Spaniel, Cavalier King Charles Spaniel). Cardiac disease was a significant comorbid disorder. Significant clinical signs included halitosis, weight loss, polyuria/polydipsia, urinary incontinence, vomiting, decreased appetite, lethargy, and diarrhea. The median survival time from diagnosis was 226 days (95% CI 112-326 days). International Renal Interest Society stage and blood urea nitrogen concentration at diagnosis were significantly associated with hazard of death due to CKD.
CONCLUSIONSAND CLINICAL IMPORTANCE: Chronic kidney disease compromises dog welfare. Increased awareness of CKD risk factors and association of blood biochemistry results with survival time should facilitate diagnosis and optimize case management to improve animal survival and welfare.
- Hypothalamitis: a diagnostic and therapeutic challenge. [JOURNAL ARTICLE]
- Pituitary 2013 May 3.
To report an unusual case of biopsy-proven autoimmune hypophysitis with predominant hypothalamic involvement associated with empty sella, panhypopituitarism, visual disturbances and antipituitary antibodies positivity. We present the history, physical findings, hormonal assay results, imaging, surgical findings and pathology at presentation, together with a 2-year follow-up. A literature review on the hypothalamic involvement of autoimmune hypophysitis with empty sella was performed. A 48-year-old woman presented with polyuria, polydipsia, asthenia, diarrhea and vomiting. The magnetic resonance imaging (MRI) revealed a clear suprasellar (hypothalamic) mass, while the pituitary gland appeared atrophic. Hormonal testing showed panhypopituitarism and hyperprolactinemia; visual field examination was normal. Pituitary serum antibodies were positive. Two months later an MRI documented a mild increase of the lesion. The patient underwent biopsy of the lesion via a transsphenoidal approach. Histological diagnosis was lymphocytic "hypothalamitis". Despite 6 months of corticosteroid therapy, the patient developed bitemporal hemianopia and blurred vision, without radiological evidence of chiasm compression, suggesting autoimmune optic neuritis with uveitis. Immunosuppressive treatment with azathioprine was then instituted. Two months later, an MRI documented a striking reduction of the hypothalamic lesion and visual field examination showed a significant improvement. The lesion is stable at the 2-year follow-up. For the first time we demonstrated that "hypothalamitis" might be the possible evolution of an autoimmune hypophysitis, resulting in pituitary atrophy, secondary empty sella and panhypopituitarism. Although steroid treatment is advisable as a first line therapy, immunosuppressive therapy with azathioprine might be necessary to achieve disease control.
- Distal renal tubular acidosis: a hereditary disease with an inadequate urinary H+ excretion. [JOURNAL ARTICLE]
- Nefrologia 2013 Mar 12.
Distal renal tubular acidosis (dRTA) or RTA type I is characterised by reduced H+ hydrogen ions and ammonium urinary excretion. In children affected by dRTA there is stunted growth, vomiting, constipation, loss of appetite, polydipsia and polyuria, nephrocalcinosis, weakness and muscle paralysis due to hypokalaemia. This work summarises progress made in dRTA genetic studies in populations studied so far. DRTA is heterogeneous and as such, transporters and ion channels are analysed which have been identified in alpha-intercalated cells of the collecting duct, which could explain cases of dRTA not associated with the hitherto studied genes. DRTA can be autosomal dominant or autosomal recessive. Autosomal recessive dRTA appears in the first months of life and progresses with nephrocalcinosis and early or late hearing loss. Autosomal dominant dRTA is less severe and appears during adolescence or adulthood and may or may not develop nephrocalcinosis. In alpha-intercalated cells of the collecting duct, the acid load is deposited into the urine as titratable acids (phosphates) and ammonium. Autosomal recessive dRTA is associated with mutations in genes ATP6V1B1, ATP6V0A4 and SLC4A1, which encode subunits a4 and B1 of V-ATPase and the AE1 bicarbonate/chloride exchanger respectively. By contrast, autosomal dominant dRTA is only related to mutations in AE1.
- [Does the T4 measurement belong in the standard blood analysis in polyuria/polydipsia?]. [Case Reports, Journal Article]
- Tijdschr Diergeneeskd 2013 Apr 1; 138(4):230-1.
- Adrenal gland function in a dog following unilateral complete adrenalectomy and contralateral partial adrenalectomy. [Journal Article]
- J Am Vet Med Assoc 2013 May 15; 242(10):1398-404.
Case Description-A 40.3-kg (88.7-lb) 6-year-old spayed female Labrador Retriever was evaluated because of acute unilateral epistaxis. Clinical Findings-During the initial evaluation of the dog, systemic hypertension and a left adrenal gland mass were detected. The left adrenal gland mass was surgically removed; results of histologic examination of the mass indicated it was a pheochromocytoma. Ten months later, the dog was evaluated because of persistent systemic hypertension and development of polyuria, polydipsia, and excessive panting. Abdominal ultrasonography revealed a mass in the cranial aspect of the right adrenal gland; results of MRI suggested the mass was a malignant tumor. Treatment and Outcome-Epistaxis resolved after treatment and resolution of severe systemic hypertension. A partial right adrenalectomy was performed to remove the right adrenal gland mass. Results of histologic examination of the mass indicated it was a well-differentiated carcinoma of the cortex of the adrenal gland. Results of ACTH stimulation tests after surgery indicated the dog had adequate adrenal gland function. Clinical Relevance-Partial adrenalectomy may be a safe and feasible treatment option to preserve adrenal gland function in dogs with small eccentrically located adrenal gland masses, particularly for dogs that have undergone removal of the contralateral adrenal gland.
- The PI3K/AKT/mTOR Signaling Pathway Is Overactivated in Primary Aldosteronism. [Journal Article]
- PLoS One 2013; 8(4):e62399.
To date, the available non-invasive remedies for primary aldosteronism are not satisfactory in clinical practice. The phosphoinositide 3-kinase (PI3Ks)/protein kinase B (PKB or AKT)/mammalian target of rapamycin (mTOR) signaling pathway is essential for tumorigenesis and metastasis in many types of human tumors, including renal cancer, adrenal carcinoma and pheochromocytoma. The possibility that this pathway is also necessary for the pathogenesis of primary aldosteronism has not yet been explored. To answer this question, we investigated the activity of the PI3K/AKT/mTOR signaling pathway in normal adrenal glands (NAGs), primary aldosteronism (PA) patients and NCI-H295R cells. METHODOLOGYPRINCIPAL FINDINGS: Between January 2005 and December 2011, we retrospectively reviewed the records of 45 patients with PA. We compared clinical characteristics (age, gender and biochemical data) and the expression of phospho-AKT (p-AKT), phospho-mTOR (p-mTOR), phospho-S6 (p-S6) and vascular endothelial growth factor (VEGF) by immunohistochemical staining and western blotting, analyzing 30 aldosterone-producing adenomas (APAs), 15 idiopathic hyperaldosteronism (IHA) tissues and 12 NAGs following nephrectomy for renal tumors (control group). Compared with the control group, most of the PA patients presented with polydipsia, polyuria, resistant hypertension, profound hypokalemia, hyperaldosteronemia and decreased plasma renin activity. Compared with normal zona glomerulosa, the levels of p-AKT, p-mTOR, p-S6 and VEGF were significantly upregulated in APA and IHA. No significant differences were found between APA and IHA in the expression of these proteins. Additionally, positive correlations existed between the plasma aldosterone levels and the expression of p-AKT and p-mTOR. In vitro studies showed that mTOR inhibitor rapamycin could inhibit cell proliferation in NCI-H295R cells in a dose- and time-dependent manner. Furthermore, this inhibitor also decreased aldosterone secretion.Our data suggest that the PI3K/AKT/mTOR signaling pathway, which was overactivated in APA and IHA compared with normal zona glomerulosa, may mediate aldosterone hypersecretion and participate in the development of PA.