Expression of adenosine deaminase and 5'-nucleotidase in artificially induced deciduoma in rat and hamster.

Enzymes adenosine deaminase (ADA) and 5-nucleotidase (5-'NT) are known to play active role in tissue/cell proliferation and differentiation. To validate this the two enzymes were studied in artificially induced deciduoma of rat and hamster. The deciduoma was induced by traumatizing one of the uterine horns of progesterone primed animals. Non traumatized horn served as control. The animals were later maintained on progesterone, given alone (Gr.I) or conjointly with estrogen (Gr.II). The weight of each uterine horn was recorded to determine the formation of deciduoma. There was no marked difference between the weights of traumatized and control horn on day 2 post-traumatization (PT), but a progressive rise was noticed after this day in both species. The ADA activity however differed, day and species wise. While in the rats of Gr.I it was low in the traumatized horn on all the days, in the hamsters it was remarkably high from day 2 to 6 PT. In the rats of Gr.II also the activity though was low in the traumatized horn, but on day 2 and 4 only; on day 6 and 7 PT it increased markedly. In hamster, on the contrary, again the enzyme activity was remarkably high on all the three days. The 5'-NT activity, however, did not show any marked difference between the two horns under Gr.I and II in both species. It was rather high in the control horn of each group. The results suggest: (I) the progesterone alone though produces a significant rise in the uterine weight of traumatized horn in both species, the ADA activity increases only in hamster, (2) under the conjoint treatment also the enzyme activity remains high in hamster; and (3) the activity of enzyme 5'-NT does not alter during the deciduoma formation in both the species.

Carcinoid tumor of common hepatic duct.

Primary carcinoid tumors of the biliary tract are extremely rare. We report a 36-year-old woman with recurrent acute cholangitis who was diagnosed to have a carcinoid in the common hepatic duct, with enlarged local nodes. She underwent local resection. I-131 metaiodobenzyl guanidine (MIBG) scanning postoperatively showed no uptake in the tumor bed.

Prenatal diagnosis of beta-thalassaemia mutations using the reverse dot blot technique.

BACKGROUND: Beta-thalassaemia is the most common genetic disorder among Indians and a number of mutations causing this disease have been reported. Since effective treatment of thalassaemia major is complicated and very expensive, prenatal diagnosis has become an important option for those at risk of having an affected foetus. We report the use of a rapid hybridization method called 'reverse dot blot' for detection of specific mutations of the beta-globin gene. METHODS: DNA was obtained from a 12-week-old foetus by chorionic villus sampling and was amplified using specific primers by the polymerase chain reaction and analysed by the reverse dot blot test. Results were available within 36 hours after sampling. RESULT: The father and mother were found to be heterozygous for codon 15 (G-A) mutation of the beta-globin gene. The foetus was normal. CONCLUSION: Reverse dot blot is a rapid and reliable technique for mutation detection in the beta-globin gene and can be useful for antenatal diagnosis.

Metabolic disposition of methyl [5-[[4-(2-pyridinyl)-1-piperazinyl] carbonyl]-1-H-benzimidazol-2-yl] carbamate in hamsters: a study to understand chemoprophylactic action against experimental Ancylostomiasis.

Methyl [5-[[4-(2-pyridinyl-1-piperazinyl] carbonyl]-1H- benzimidazol-2-yl] carbamate (CDRI Compound 81-470) exhibits a long prophylactic action against experimental ancylostomiasis, when given parenterally but not orally. To find out an explanation for such a behaviour, metabolic disposition studies were performed in hamsters using [3H] compound 81-470. Following intramuscular administration, the compound was found to form a depot at the site of injection and to remain there in substantial amount for more than 7 weeks. The compound was fairly distributed in all the organs studied and the presence of radioactivity could be easily detected up to 7 weeks of observation period. The compound was very slowly eliminated from the body and only 38% of the radioactivity could be recovered in the urine and faeces during 14 days. The oral dose, to the contrary, was poorly absorbed and more than 62.8% was excreted in the faeces within 48 hr. Consequently, this dose yielded lesser area under plasma curve. More than 95% of the oral dose was eliminated within a week and hardly and radioactivity could be detected in the tissues after day 14. In accord with this pattern, in blood also the im dose was detected up to 7 weeks while the orally given compound reached undetectable level within 6 days only. The lower clearance and prolonged stay in the body of the im dose compared to quick elimination of the oral dose may be responsible for the long chemoprophylactic action of compound 81-470 when given through im route.

Carboline antifilarials: effects on carbohydrate metabolising enzymes in Litomosoides carinii female.

Two antifilarial compounds, viz., 90/55 (7-oxo-1-phenyl-8, 14-dihydropyrido (3,4-b) imidazo (1,2-c) quinazolo (4,5-g) and 87/639 (6-Nitro-1-phenyl-9H-pyrido (3,4-b) indole at 0.5 and 2.0 micron concentrations substantially inhibited glucose uptake and increased lactate production by L. carinii during in vitro incubation for 2 hr. The treated parasites, showed increased activities of glycogen phosphorylase, phosphofructokinase and pyruvate kinase. Hexokinase and fumarate reductase activities level in the worms were significantly lowered. Therefore it appears that both the compounds kill adult L. carinii by interfering with its carbohydrate metabolism.

Adenosine deaminase activity in pleural fluid--a diagnostic test of tuberculous pleural effusion.

Adenosine deaminase (ADA) activity in pleural fluids was studied in 47 patients with pleural effusion of different etiology. Patients were divided into two groups: Group I - Tuberculous pleural effusion (21 patients): Group II - Non tuberculous effusion (26 patients) and these included malignant pleural effusion (9 cases), synpneumonic pleural effusion (9 cases) and transudative pleural effusion (8 cases). The mean ADA activity was 64.67 IU/L +/- 21.68 in group I and 6.99 +/- 3.69 in Group II. Increased mean pleural fluid ADA activity in tuberculous pleural effusion was highly significant (p < 0.001) when compared with pleural effusion of non-tuberculous etiology. Based on lowest value of ADA activity found in tuberculous pleural effusion (30 IU/L), the test has a sensitivity and specificity of 1.

Alterations in metabolic activity of Cysticercus fasciolaris on some anthelmintic treatments.

Effect of candidate compounds 81-470 i.e. methyl [5[4-(2-pyridinyl)-1-piperazinyl]carbonyl]-1H-benzimidazole-2-yl]- carbamate and 86-162 i.e. methyl-5(6)-(alpha-hydroxyphenyl methyl) benzimidazole-2-carbamate along with reference drugs mebendazole and praziquantel on energy metabolism of C. fasciolaris recovered from rats treated with single dose of 500 mg/kg, ip was investigated. All the drugs significantly lowered the rate of uptake of glucose and alanine by the parasite. Suppression in the formation of lactate, the major end-product, was also noticed. Nonetheless the ratio of lactate produced versus the substrates consumed was not substantially affected. The recovered cysticerci also possessed less glycogen and ATP compared to the normal parasites. Although the effects exerted by the drugs were of the identical nature, they significantly differed in the magnitude of their action. Mebendazole followed by praziquantel maximally affected all the above metabolic activities while 86-162 proved to be the weakest in action. The results suggest that the examined drugs exert their chemotherapeutic activity by interfering with uptake of glucose and alanine but do not significantly alter their catabolism.

Impact of surface modifications of Acanthocheilonema viteae microfilariae on cell adhesion.

Exposure of A. viteae microfilariae to various lectins reduced their capacity to react with the peritoneal exudate cells of the host, Mastomys natalensis. Sugars corresponding to these lectins with the exception of N-acetyl glucosamine, did not affect the adhesion per se. They however, protected the parasite against the adverse effect of lectins. Neuraminidase and chitinase also suppressed adhesion capacity of the microfilariae. Except sodium dodecylsulphate which enhanced cell attachment, other surfactants inhibited this reaction considerably. The results indicate that antibody dependent adhesion of the microfilariae with the macrophages involves surface moieties of the parasite, where N-acetylglucosamine acts as the principal sugar residue. Participation of -SH groups also is inferred from the observations that p-chloromercuribenzoate and dithiobis-(2-nitrobenzoic acid) inhibited cell attachment and dithiothreitol provided protection against these agents.

Ancylostoma ceylanicum: ATP production and effect of anthelmintics.

Dicarboxylic acids and a few amino acids were found to support mitochondrial phosphorylation in A. ceylanicum. Anaerobiasis markedly reduced this activity. Maximum effect was observed on succinate supported phosphorylation which in anaerobic atmosphere yielded only 2% ATP compared to that in the presence of air. Known as well as candidate anthelmintics significantly inhibited ATP formation. Mebendazole, amongst them, registered greatest effect. Oxygen consumption by the mitochondria exhibited poor response to the action of anthelmintics other than praziquantel.

Xanthine oxidase, superoxide dismutase, catalase and lipid peroxidation in Mastomys natalensis: effect of Dipetalonema viteae infection.

Status of xanthine oxidase, superoxide dismutase, catalase and lipid peroxidation, the enzymes metabolizing reactive oxygen intermediates in liver, lungs and spleen of M. natalensis during D. viteae infection was investigated. Xanthine oxidase and lipid peroxidation exhibited stimulation, while superoxide dismutase and catalase showed depression in liver and spleen of the infected animals. The filarial infection therefore appears to create O2 toxicity in these tissues. Lungs, on the other hand was found safe as it possessed elevated xanthine oxidase, superoxide dismutase and catalase. Lipid peroxidation in lungs operated below the control level. The impact of these changes in the establishment and development of the infection has been discussed.

Binding properties of diethylcarbamazine.

Diethylcarbamazine (DEC) reacted with liver cell plasma membrane of rodent hosts-cotton rat, albino rat and Mastomys natalensis exhibiting the presence of both saturable and unsaturable components. The presence of lectins or sugar derivatives did not affect the binding significantly. The drug showed similar binding pattern with serum but the saturation was reached at a much lower concentration of the ligand. Data obtained with a variety of macromolecules, particularly with the homopolymers of amino acids indicate that DEC does not require any specific constituent of the membrane for binding. The nonspecific nature of DEC binding does not provide any convincing clue for the accumulation of microfilariae specifically in the liver following the drug treatment.

Effects of methyl [5 [[4-(2-pyridinyl)-1-piperazinyl]carbonyl]-1H-benzimidazol-2-yl] carbamate on energy metabolism of Ancylostoma ceylanicum and Nippostrongylus brasiliensis.

Effects of methyl [5[[4-(2-pyridinyl)-1-piperazinyl] carbonyl] 1H-benzimidazol-2-yl] carbamate (CDRI Comp. 81-470) and mebendazole on the energy metabolism of A. ceylanicum and N. brasiliensis were compared. At 10 and 50 microM concentration both compounds inhibited glucose uptake and its conversion into metabolic endproducts. The shift towards the increased production of lactic acid appeared to be the result of inhibition of PEP carboxykinase and increase in LDH activity. The compounds also caused significant inhibition of ATP production in mitochondria.

Enzymes of carbohydrate metabolism of Cotugnia digonopora and their activity in the presence of anthelmintics, in vitro.

Cotugnia digonopora, a fowl cycllophyllidean cestode, was found to possess most of the enzymes, associated with the glycolytic sequence and phosphoenolpyruvate branch point, in the cytosol fraction. Enzymes of malate metabolism were predominantly mitrochondrial. Anthelmintic agents inhibited hexokinase, phosphofructokinase, glucose-6- phosphate dehydrogenase, malate dehydrogenase, fumarate reductase, and malic enzyme. In intact worms this effect was significantly reduced. However, the activities of glycogen Phosphorylase and pyruvate kinase were significantly enhanced.