To study the effects of chronic metabolic acidosis on the metabolism of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] rats were given either a low calcium diet (LCD) (0.002% calcium) or chow (1.2% calcium); ammonium chloride (NH4Cl) was added (1 or 1.5%) to the drinking water of some rats eating LCD or chow while others served as nonacidotic controls. LCD increased circulating 1,25(OH)2D3 levels from 46 +/- 14 to 204 +/- 24 pg/ml (P less than 0.001) in the absence of NH4Cl; 1.5% NH4Cl prevented the increase in 1,25(OH)2D3 (25 +/- 6 vs. 27 +/- 8 pg/ml (P, NS) but 1% NH4Cl did not (50 +/- 12 vs. 161 +/- 23 pg/ml; P less than 0.001). Acidosis suppressed neither serum immunoreactive parathyroid hormone (PTH) nor urine cAMP response to LCD. Although total serum calcium and phosphorus showed no regular changes with NH4Cl, acidosis raised blood ionized calcium in rats fed either chow or LCD, and serum 1,25(OH)2D3 levels were inversely correlated with ionized calcium (r = 0.714; P less than 0.001) during LCD. Chronic NH4Cl acidosis prevented serum 1,25(OH)2D3 from rising during LCD, independent of changes in PTH secretion, cAMP generation, or serum phosphorus. The absence of a 1,25(OH)2D3 response may be due to increased ionized calcium produced by acidosis.
Previous studies have shown that thiazide diuretic agents reverse secondary hyperparathyroidism and reduce circulating 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and intestinal calcium absorption rates in patients with idiopathic hypercalciuria of the renal-leak variety. We have investigated whether thiazides can reverse the secondary increase in serum parathyroid hormone (PTH) and 1,25(OH)2D3 levels or intestinal calcium absorption induced by feeding rats a diet low in calcium (LCD, 0.02% calcium) but adequate in phosphorus and vitamin D. We found that LCD increased circulating immunoreactive PTH [chow vs. LCD, 0.52 +/- 0.06 vs. 1.06 +2- 0.1 (SE) ng/ml, P less than 0.001], 1,25(OH)2D3 (chow vs. LCD, 101 +/- 15 vs. 325 +/- 38 pg/ml, P less than 0.001), calcium uptake by everted gut sacs from duodenum, ileum, and descending colon, and net calcium absorption by descending colon studied in Ussing chambers in vitro. Chlorothiazide (CTZ) prevented the increase in PTH during LCD (chow + CTZ vs. LCD + CTZ, 0.69 +/- 0.07 vs. 0.73 +/- 0.06, NS) but not the increase in 1,25(OH)2D3 (chow + CTZ vs. LCD + CTZ, 88 +/- 10 vs. 277 +/- 31, P less than 0.002) or intestinal calcium transport. The drug caused no change in serum 1,25(OH)2D3 or intestinal calcium absorption in rats fed normal chow. In rats given exogenous 1,25(OH)2D3 to stimulate intestinal calcium absorption, CTZ reduced urine calcium excretion greatly but did not alter intestinal calcium absorption.
BACKGROUND The emergence of drug resistant mycobacterium has become a significant public health problem creating an obstacle to effective tuberculosis (TB) control. Freedom from TB is possible with timely, regular, complete treatment, with assurance, prevention and management of side effects of antitubercular drugs. Present study was conducted to evaluate common and rare adverse drug reactions (ADR) of CAT IV and CAT V to analyse demographic, radiological and bacteriological profile and treatment outcome in MDR & XDR patients. We wanted to evaluate the common and rare adverse drug reactions of intensive phase treatment of Multi Drug Resistant Tuberculosis (MDR) and Extensively Drug Resistant Tuberculosis (XDR) as per WHO-UMC Causality Assessment Scale. METHODS 76 patients of MDR and XDR Tuberculosis were admitted in DR-TB (Drug Resistant TB) centre, Burdwan Medical College and Hospital and the adverse drug reaction profile of 2 nd line drugs were analysed during the intensive phase from April 2016 to September 2017 after fulfilling the inclusion and exclusion criteria. Treatment was given as per the guidelines of Revised National TB Control Program PMDT (Programmatic Management of Drug-Resistant TB). RESULTS Adverse drug reactions on GI system were nausea 73 patients (96.10%), vomiting 70 (92.10%), acidity 41 (53.9%), and sulphurous belching and hepatitis 1 (1.31%) each. Peripheral neuropathy, hearing deficit, myopathy, skin rashes, hepatitis, nephrotoxicity, cardiac toxicity and convulsion were also observed. In psychosis, 3 (3.95%) had depression and made suicidal attempt. 1 each (1.31%) in hallucination and paranoia. 5 patients (6.58%) had blurring of vision, 2 patients (3.95%) had redness of eyes and one (1.31%) had eye irritation. Reactions were common in first 60 days of the regimen and in patients with BMI ≤18. CONCLUSIONS Vigilant monitoring is required for these patients during the initial period and sputum smear and culture conversion is very well correlated with clinical and radiological improvement.
A B S T R A C T BACKGROUNDGlobally, an estimated 10.0 million people developed Tuberculosis in 2017. Side effects and toxicity of the first line anti-tubercular drugs were hepatotoxicity, skin rash, and joint pain. If hepatotoxicity develops on reintroduction of treatment with the same regimen, then treatment should be started with hepato-safe regimen. Majority of the reports have used an elevated Alanine Transaminase (ALT) or Aspartate Transaminase (AST) of 3 times upper limit of normal range (ULN) with symptoms attributable to liver injury or 5 times ULN of ALT or AST without symptoms to define hepatotoxicity. Due to paucity of studies regarding adaptive response, this study was conducted to find out the proportion of anti-tubercular drug (ATD) induced hepatitis during Anti-TB treatment and frequency of adaptive changes in Liver Enzymes during the course of anti TB treatment. RESULTSIn 83.3% patients only SGPT level was elevated, while in 71% SGOT was only elevated. Both SGPT and SGOT were elevated in 66.7% of cases. Only 1.8% cases were observed with elevated SGPT and SGOT on six occasions. Only 16.7% had no elevation in SGPT and 28.9% had no elevation in SGOT. Most of the patients had asymptomatic elevation of liver enzymes and didn't need any treatment interruption. 4.38% patients developed drug induced hepatitis and needed treatment interruption for about two weeks and all were reintroduced with the same regimen successfully. CONCLUSIONSDrug induced liver function abnormality is a common occurrence during the course of anti-TB treatment. Most patients show tolerance to anti-TB drugs and get adjusted after transient rise in liver enzymes. Concomitant use of hepatotoxic agent should be avoided as far as possible.
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