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Biomedical subjects

M Tandon

Publications and source records attributed to M Tandon.

At least 55 records · Page 3Linked to original sources

Assessment of iodine deficiency in selected blocks of east and west Champaran districts of Bihar.

OBJECTIVE: A survey conducted in 1964 reported a goitre prevalence of 40.3% in East and West Champaran districts of Bihar. No recent survey has been documented on the prevalence of iodine deficiency in these districts. The present study was therefore undertaken (i) to assess the prevalence of IDD in these districts, and (ii) to estimate the iodine content of salt consumed by population. METHODOLOGY: In each district, one block was selected. In each block more than 630 children in the age group of 6-12 years were included in the study and were clinically examined. Urine samples were collected from 261 children and were analyzed using standard laboratory procedures. A total of 456 salt samples were collected from children and 35 from traders from the two districts and analyzed using the standard iodometric titration method. RESULTS: The total goiter prevalence was 11.6%. The percentage of children with < 2, 2.0-4.9, 5.0-9.9 and > or = 10 mcg/dl of urinary iodine excretion level were 12.3, 13.4, 23.4 and 51.0, respectively. The median urinary iodine excretion of the children was 10.0 mcg/dl. None of the families were consuming salt with a nil iodine content and about 29.3%, were consuming salt with less than 15 ppm of iodine. Of the 35 salt samples collected from traders, all had iodine and about 17% had less than 15 ppm of iodine. CONCLUSION: The study stresses the need for strengthening the existing system of monitoring of quality of salt being provided in the East and West Champaran districts by Government of Bihar.

Child↗

alpha-Trifluoromethyl-beta-alanyl glycine (F3MBAG): a novel mammalian metabolite of trifluridine (F3TdR).

19F NMR spectroscopy has been used to study further the metabolism of 5-trifluoromethyl-2'-deoxyuridine (trifluridine; F3TdR). The synthesis and characterization of alpha-trifluoromethyl-beta-alanyl glycine (F3MBAG), a putative new metabolite of F3TdR, are now reported. This study describes ex vivon and in vivo detection of F3MBAG and other previously reported metabolites of trifluridine, using 19F NMR spectroscopy, in male BALB/C mice bearing EMT-6 tumors. A parallel 19F NMR spectroscopic study was also performed on rats dosed with F3TdR, to observe the qualitative pattern of F3TdR metabolism in another species. Unexpectedly, 5-trifluoromethyl-5,6-dihydroxyuracil (DOHF3T), alpha-trifluoromethyl-beta-ureidopropionic acid (F3MUPA) and fluoride, which result from the metabolic degradation of F3TdR and which were detected in various biological samples from mice dosed with F3TdR, could not be identified in rat urine or in homogenized tissue extracts. The presence of these metabolites in intact tissues is uncertain since in this study 19F NMR spectroscopy of these samples always displayed a broad resonance "hump" across the range of chemical shifts that would encompass these metabolites. No clear explanation for the loss of spectroscopic resolution in this region has been rationalized. N-Carboxy-alpha-trifluoromethyl-beta-alanine (F3MBA-CO2), alpha-trifluoromethyl-beta-alanyl alanine (F3MBAA) and N-acetyl-alpha-trifluoromethyl-beta-alanine (Ac-F3MBA) were synthesized and characterized, but were not detected as metabolites in any of the biological specimens examined.

Animals↗

Plexogenic angiopathy in pulmonary intralobar sequestrations: pathogenetic mechanisms.

Vascular remodeling to form plexiform (glomoid) lesions is a little-known manifestation of intralobar pulmonary sequestration. We describe histologic and immunohistochemical features of these lesions in resected specimens from three subjects aged 3, 19, and 28 years. The vascular changes, which included medial and intimal thickening, angioblastic proliferation, plexiform lesions, and dilation lesions, occurred in a setting of hypoxia, chronic inflammation, and high pressure and flow via a systemic arterial supply. We demonstrated strong immunoreactivity of the angioblastic tissue and the plexiform lesions with antibodies to muscle actin, alpha-smooth muscle actin, and vimentin, and weak to absent reactivity with antibody to desmin. We suggest that in these sequestrations plexiform lesions develop via angioblastic proliferation at arterial branch points and that dilation lesions develop from subsequent expansion of distal anastomoses.

Actins↗

Detection of new metabolites of trifluridine (F3TdR) using 19F NMR spectroscopy.

The metabolism of 5-trifluoromethyl-2'-deoxyuridine (trifluridine, F3TdR) in male BALB/C mice has been studied by 19F NMR spectroscopy. Contrary to previous reports, a number of fluorinated metabolites were observed in urine, whole livers and blood samples taken from mice after i.p. injection of F3TdR. The present study describes the identification of two new metabolites in mouse urine using the 19F NMR technique. The NMR of crude urine showed the presence of F3TdR 5-trifluorothymine (F3T), the newly-identified metabolites, 5-trifluoromethyl-5,6-dihydrouracil (DHF3T) and 5-trifluoromethyl-5,6-dihydroxyracil (DOHF3T), and several new, as yet unidentified fluorinate metabolites. These two new metabolites were characterized by comparison to authentic compounds prepared synthetically from F3T.

Animals↗

Synthesis and biological activity of 5-(2,2-difluorocyclopropyl)-2'-deoxyuridine deoxyuridine diastereomers.

The synthesis of the two diastereomers (9 and 10) of 5-(2,2-difluorocyclopropyl)-2'-deoxyuridine are described. Their antiviral and cytotoxic activities were determined, in comparison with (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and 5-fluoro-2'-deoxyuridine (FDU), respectively. 5-[(1R)-2,2-Difluorocyclopropyl]-2'-deoxyuridine (10) was the most active antiviral agent against HSV-1 (IC50 = 5 micrograms/ml) relative to BVDU (IC50 = 0.082 micrograms/ml), and cytotoxic agent in the CCRF-CEM (IC50 = 230 microM) screen relative to FDU (IC50 = 4.7 x 10(-3) microM). The 5-[(1S)-2,2-difluorocyclopropyl] diastereomer was inactive in both screens. Partition coefficients (P) and affinity for the mouse erythrocyte nucleoside transporter (Ki) were not determinants of antiviral or cytotoxic activities. However, the (1R)-diastereomer (10) was more resistant to glycosidic bond cleavage by thymidine phosphorylase than the (1S)-diastereomer (9).

Animals↗

Synthesis of the diastereomers of 5-(2,2-dichlorocyclopropyl)- and 5-(2-chlorocyclopropyl)-2'-deoxyuridine, and the antiviral and cytotoxic activity of these and bromo analogues.

Syntheses of the two diastereomers (5a and 6a) of 5-(2,2-dichlorocyclopropyl)-, and of the four diastereomers (7a-10a) of 5-(2-chlorocyclopropyl)-2'-deoxyuridine are described. These, and corresponding diastereomers (5b and 6b; 7b-10b) of 5-(2,2-dibromocyclopropyl)- and 5-(2-bromocyclopropyl)-2'-deoxyuridine (prepared in an earlier investigation) were examined for antiviral and cytotoxic activity, in comparison with (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and 5-fluoro-2'-deoxyuridine (FDU). 5-[(1R,2R)-2-Chlorocyclopropyl]-2'-deoxyuridine (9a) was the most active antiviral agent (IC50 = 25 micrograms/ml) against herpes simplex virus type 1 (HSV-1) relative to BVDU (IC50 = 0.082 microgram/ml). Compounds having the R configuration at the C-1 and/or C-2 positions of the 5-[2,2-dichloro(or 2-chloro)cyclopropyl] substituent exhibited the most potent antiviral activity. The cytotoxic activities of the 5-(2,2-dihalocyclopropyl)- (5-6a and b) and 5-(2-halocyclopropyl)- diastereomers (7-10a and b) were dependent upon both the configuration of the C-1 and/or C-2 cyclopropyl carbons and the nature of the halogeno (Cl, Br) substituent. 5-[(1R)-2,2-Dichlorocyclopropyl]-2'-deoxyuridine (6a) was the most active cytotoxic compound in the CCRF-CEM (IC50 = 17 microM) and HL-60 (IC50 = 64 microM) screens relative to FDU, which exhibited IC50 values of 4.7 x 10(-3) and 77 microM in these respective screens.

Antineoplastic Agents↗

Tetrazoles as potent anti-inflammatory agents.

Various new tetrazoles were tested for their anti-inflammatory activity against carrageenin-induced paw oedema in albino rats. Among these, two most potent derivatives were evaluated in detail using cotton pellet implantation methods in albino rats of either sex. These two active analogues were also tested for their analgesic activity in albino mice and ulcerogenic liability in albino rats. All derivatives of the present series were evaluated for their antiproteolytic activity. The toxicity of the compounds was assessed by determination of their approximate LD50 in albino mice. An attempt has also been made to establish the structure activity relationship.

Animals↗

Acute liver failure. Experience with 145 patients.

Acute liver failure (ALF) is an uncommon but serious disease still carrying a high mortality. This report describes one of the largest series of cases of acute failure, managed on a simple intensive supportive therapeutic regimen. One hundred fifty-eight patients with ALF were admitted to the Rajgarhia Liver Unit of the All-India Institute of Medical Sciences (AIIMS) during the period July 1976 to December 1981. Data from 145 were completed and analyzed for this report. Of the patients, 85.4% were below the age of 40 years. The female-to-male ratio was 1.3:1. Of the 77 women in the reproductive age group, 59.7% were pregnant. All cases of ALF were secondary to viral hepatitis. Cerebral edema, bleeding, infection, and renal failure were seen in 57.2, 57.2, 39.3, and 16.5% of patients, respectively. Overall survival was 28.9% of patients. It was 33% below the age of 40 years and only 4.8% above this age. Pregnancy did not adversely affect the prognosis. Survival was related to grade of coma, being 22.8% for patients in Grade IV coma and 62% for patients in Grade I coma. In fatal cases the immediate complications resulting in death were cerebral edema (63%), bleeding (30%), renal failure (10.6%), and infection (8.7%). Presence of HBsAg, a serum bilirubin of over 20 mg%, and serum sodium less that 119 mEq/liter were indicators of poor prognosis. A simple, intensive, support therapy yielded results comparable to those reported by centers using a variety of complex therapeutic regimens.

Acute Disease↗

Acute hepatic failure due to Plasmodium falciparum liver injury.

Nine patients with acute liver failure due to Plasmodium falciparum liver injury admitted to the Rajgarhia Liver Unit of the All-India Institute of Medical Sciences during 1982-84 are presented. The liver was palpable in all the patients, and eight had splenomegaly. Investigations revealed mild to moderate abnormality in liver function tests. All were negative for the markers of acute infection due to hepatitis A and B viruses. Blood film examination showed P. falciparum alone in seven and along with P. vivax in the remaining two patients. Liver histology, which was identical in all eight patients where liver biopsy was done, showed centrizonal necrosis and hyperplastic Kupffer cells loaded with malarial pigment. All the patients recovered with specific anti-malarial and supportive treatment. Our observations suggest that malaria due to P. falciparum may present as jaundice and encephalopathy which stimulates acute hepatic failure due to fulminant hepatitis.

Acute Disease↗

Novel thiazolidinones as potent anti-inflammatory and analgesic agents.

Various new butyridenyl-2-hydroxybenzylidenyl-1,3-thiazolidinones were synthesized and characterized by elemental analyses, IR and PMR spectral data. The compounds were evaluated for their ability to afford protection against inflammation by carrageenin-induced oedema and cotton pellet implantation in albino rats of either sex. The active derivatives of the present series were also tested for their analgesic activity against aconitine-induced writhing in albino mice and ulcerogenic activity in albino rats. The toxicity of the compounds was reflected by determination of their approximate LD50 in albino mice. An attempt has also been made to correlate their structure-activity relationship.

Aconitine↗