Design,synthesis, characterization,antibacterial and antifungal activities of a novel class of 5,7-diaryl-4,4-dimethyl-4,5,6,7-tetrahydropyridino[3,4-d]-1,2,3-selenadiazoles

Compound 26 is more potent against Escherichia coli. and 24 is more active against Staphylococcus aureus, β-Heamolytic streptococcus, Vibreo cholerae, Salmonella typhii, and Shigella flexneri than the standard drug ciprofloxacin. Moreover, of all the compounds tested, 26 is more effective against Aspergillus flavus and Mucor, than the standard drug fluconazole.     

Standard dimensions forcis N-methyl peptide unit and flexibility ofcis peptide units

The mean dimensions of thecis N-methyl peptide unit have been arrived at by analysing the crystal structure data on compounds containing such units. These dimensions can be used as standard in conformational studies on cyclic peptides. While the bonds meeting at C are almost coplanar, those meeting at N show a slight pyramidal disposition. A comparison of the dimensions of the normal and N-methylatedcis peptide units show that there are perceptible differences in the parameters connected with N. In addition, the flexibility of thecis peptide unit has been analysed by studying the distribution of the parameters in different classes of compounds such as cyclic di, tri and higher peptides. The salient features are: (i) The angle C^αCN in cyclic dipeptide and the angle C^δNC^α in higher peptides tend to be lower, when the peptide unit is associated with a prolyl residue; (ii) in cyclic tripeptides the internal anglesviz., C^αCN and CNC^α are significantly larger thereby increasing the intra-annular space; (iii) the bond C^α-C is distinctly shorter when it occurs in cyclic dipeptides. The results lead to the conclusion that thecis peptide unit takes up aneed-based flexibility in its dimension.     

Short course chemotherapy for tuberculous lymphadenitis in children.

OBJECTIVE--To assess the efficacy of a short course chemotherapy regimen for treating tuberculosis of the lymph nodes in children. DESIGN--Open, collaborative, outpatient clinical trial. SETTING--Outpatient department of the Tuberculosis Research Centre, paediatric surgery departments of the Institute of Child Health and Hospital for Children and the Government Stanley Hospital, Madras, South India. PATIENTS--Children aged 1-12 years with extensive, multiple site, superficial tuberculous lymphadenitis confirmed by biopsy (histopathology or culture). INTERVENTIONS--Patients were treated with a fully supervised intermittent chemotherapy regimen consisting of streptomycin, rifampicin, isoniazid, and pyrazinamide three times a week for two months followed by streptomycin and isoniazid twice a week for four months on an outpatient basis. Surgery was limited to biopsy of nodes for diagnosis and assessment. MAIN OUTCOME MEASURES--Response to chemotherapy was assessed by regression of lymph nodes and healing of sinuses and abscesses during treatment and follow up. Compliance with treatment and frequency of adverse reactions were also estimated. RESULTS--197 Patients were admitted to the study and 168 into the analysis. The regimen was well tolerated and compliance was good with 101 (60%) patients receiving the prescribed chemotherapy within 15 days of the stipulated period of six months. Those whose chemotherapy extended beyond that period received the same total number of doses. Clinical response was favourable in most patients at the end of treatment. Sinuses and abscesses healed rapidly. Residual lymphadenopathy (exceeding 10 mm diameter) was present in 50 (30%) patients at the end of treatment; these nodes were biopsied. Fresh nodes, increase in size of nodes, and sinuses and abscesses occurred both during treatment and follow up. After 36 months of follow up after treatment only 5 (3%) patients required retreatment for tuberculosis. CONCLUSION--Tuberculous lymphadenitis in children can be successfully treated with a short course chemotherapy regimen of six months.     

Interaction of alcohol and protein deficiency on rat brain synaptosomal (Na+−K+)-ATPase

Administration of low amounts of ethanol for a prolonged period increases rat brain synaptosomal (Na⁺–K⁺)-ATPase activity, the increase being less in the protein deficient rats. The adaptive mechanism to offset the stress imposed by the continued presence of ethanol seems to be depressed by low plane of nutrition. In vivo and in vitro effects of ethanol on (Na⁺–K⁺)ATPase seems to be different.     

Effect of Maternal Alcohol Consumption on the Lipid Composition of CNS in the Offspring

Maternal alcohol consumption at a level that does not affect calorie intake increases cholesterol concentration and content as well as incorporation of labeled glucose into cholesterol in the brain and spinal cord of newborn rat pups. Continued consumption of alcohol during lactation also affects the galactolipid concentration in the brain and spinal cord of pups at 21 days of age, and this increase seems mainly to be due to an increase in content of myelin lipids. Analysis of myelin shows that the concentration of phospholipids also increases in this fraction. The increase in incorporation of labeled glucose into these membrane lipids suggests an increase in the synthesis of these lipids, which prevents fluidization of the membrane by alcohol. That in the brainstem the increase in levels of cholesterol and galactolipids is higher than in other regions and that there is also an increase in content of sphingomyelin, phosphatidylcholine, and phosphatidylethanolamine suggest that the brainstem needs better protection against fluidization.     

Carcinogen-nucleic acid interactions: equilibrium binding studies of aflatoxins B1 and B2 with DNA and the oligodeoxynucleotide d(ATGCAT)2

Equilibrium binding is believed to play an important role in directing the subsequent covalent attachment of many carcinogens to DNA. We have utilized UV spectroscopy to examine the non-covalent interactions of aflatoxin B1 and B2 with calf thymus DNA, poly(dAdT):poly(dAdT), and poly(dGdC):poly(dGdC), and have utilized NMR spectroscopy to examine non-covalent interactions of aflatoxin B2 with the oligodeoxynucleotide d(ATGCAT)2. UV-VIS binding isotherms suggest a greater binding affinity for calf thymus DNA and poly(dAdT):poly(dAdT) than for poly(dGdC):poly(dGdC). Scatchard analysis of aflatoxin B1 binding to calf thymus DNA in 0.1 M NaCl buffer indicates that binding of the carcinogen at levels of bound aflatoxin less than 1 carcinogen per 200 base pairs occurs with positive cooperativity. The cooperative binding effect is dependent on the ionic strength of the medium; when the NaCl concentration is reduced to 0.01 M, positive cooperativity is observed at carcinogen levels less than 1 carcinogen per 500 base pairs. The Scatchard data may be fit using a "two-site" binding model [L.S. Rosenberg, M.J. Carvlin, and T.R. Krugh, Biochemistry 25, 1002-1008 (1986)]. This model assumes two independent sets of binding sites on the DNA lattice, one a high affinity site which binds the carcinogen with positive cooperativity, the second consisting of lower affinity binding sites to which non-specific binding occurs. NMR analysis of aflatoxin B2 binding to d(ATGCAT)2 indicates that the aflatoxin B2/oligodeoxynucleotide complex is in fast exchange on the NMR time scale. Upfield chemical shifts of 0.1-0.5 ppm are observed for the aflatoxin B2 4-OCH3, H5, and H6a protons. Much smaller chemical shift changes (less than or equal to 0.06 ppm) are observed for the oligodeoxynucleotide protons. The greatest effect for the oligodeoxynucleotide protons is observed for the adenine H2 protons, located in the minor groove. Nonselective T1 experiments demonstrate a 15-25% decrease in the relaxation time for the adenine H2 protons when aflatoxin B2 is added to the solution. This result suggests that aflatoxin B2 protons in the bound state may be in close proximity to these protons, providing a source of dipolar relaxation. Further experiments are in progress to probe the nature of the aflatoxin B1 and B2 complexes with polymeric DNA and oligodeoxynucleotides, and to establish the relationship between the non-covalent DNA-carcinogen complexes observed in these experiments, and covalent aflatoxin B1-guanine N7 DNA adducts.