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Biomedical subjects

K Venkatesan

Publications and source records attributed to K Venkatesan.

At least 19 recordsLinked to original sources

Comparative evaluation of Löwenstein-Jensen proportion method, BacT/ALERT 3D system, and enzymatic pyrazinamidase assay for pyrazinamide susceptibility testing of Mycobacterium tuberculosis.

Pyrazinamide (PZA) is an important first-line antituberculosis drug because of its sterilizing activity against semidormant tubercle bacilli. In spite of its very high in vivo activity, its in vitro activity is not apparent unless an acidic environment is available, which makes PZA susceptibility testing difficult by conventional methods. The present study was, therefore, planned to assess the performance of the colorimetric BacT/ALERT 3D system and compare the results with those from conventional tests, i.e., the Löwenstein-Jensen (LJ) proportion method (pH 4.85) and Wayne's pyrazinamidase (PZase) assay, using 107 clinical isolates. The concordance among all of these tests was 89.71% after the first round of testing and reached 92.52% after resolution of the discordant results by retesting. Prolonged incubation of the PZase tube for up to 10 days was found to increase the specificity of the PZase test. The concordances between LJ proportion and BacT/ALERT 3D, LJ proportion and the PZase assay, and BacT/ALERT 3D and the PZase assay were found to be 99.06%, 93.46%, and 92.52%, respectively. Using the LJ results as the gold standard, the sensitivities of BacT/ALERT 3D and the PZase assay were 100 and 82.85%, respectively, while the specificity was 98.61% for both of the tests. The difference between the sensitivities of BacT/ALERT 3D and the PZase assay was significant (P = 0.025). The mean turnaround times for the detection of resistant and susceptible results by BacT/ALERT 3D were 8.04 and 11.32 days, respectively. While the major limitations associated with the PZase assay and the LJ proportion method are lower sensitivity in previously treated patients and a longer time requirement, respectively, the BacT/ALERT 3D system was found to be rapid, highly sensitive, and specific.

Amidohydrolases↗

Volume-demanding cis-trans isomerization of 1,2-diaryl olefins in the solid state.

Volume-demanding cis-trans photoisomerization of the aromatic substituted alkenes 1-3 in the solid state at room temperature and at 50 degrees C is presented. Alkene 3 did not undergo the cis-trans isomerization in the solid state either at room temperature or at 50 degrees C. The importance of the presence of void space near the reaction center to facilitate the large volume change during cis-trans photoisomerization is discussed.

Journal Article↗

Copper- and ligand-free Sonogashira reaction catalyzed by Pd(0) nanoparticles at ambient conditions under ultrasound irradiation.

The Sonogashira reaction proceeds at ambient temperature (30 degrees C) in acetone or room-temperature ionic liquid, 1,3-di-n-butylimidazolium tetrafluoroborate ([bbim]BF4), as solvent under ultrasound irradiation to give enhanced reaction rates, excellent chemoselectivity, and high yields in the absence of a copper cocatalyst and a phosphine ligand. TEM analysis showed the formation of stable, crystalline, and polydispersed Pd(0) nanoparticles as catalyst for the reaction.

Journal Article↗

Large molecular motions are tolerated in crystals of diamine double salt of trans-chlorocinnamic acids with trans-1,2-diaminocyclohexane.

Contrary to the general assumption that photoreactions in crystals may not proceed with large molecular motions, a pedal-like motion prompted by electronic excitation is believed to be involved during the beta-dimer formation from the crystals of the diamine double salt of trans-2,4-dichlorocinnamic acid and trans-1,2-diaminocyclohexane.

Journal Article↗

Location of Zn within the Mg12(LaxCe1-x) lattice by X-ray incoherent channelling patterns.

Systematic electron diffraction studies on intermetallic precipitates formed within a lightweight Mg-RE-Zn alloy (RE = La or Ce) identify these to be of structural type Mn(12)Th (space group I4/mmm). Analytical electron microscopy yields an overall composition of Mg(12)(La(x)Ce(1-x)) with x ~ 0.43, with 1 at.% Zn incorporated within the lattice. Variations in characteristic X-ray emission rates, as an electron beam is rocked near zone-axis orientations, are used to form two-dimensional channelling patterns, termed X-ray incoherent channelling patterns. This channelling contrast enables a specific sublattice site that is occupied by Zn to be unambiguously identified within the Mg(12)RE lattice. The particular sublattice site is denoted by the Wyckoff letter f, and is one of the three different Mg sublattice sites f, i and j. Of these three sites, the Wigner-Seitz cell that is centred on the f sublattice site has the largest Mg-RE interatomic distance, and therefore the f site is expected to be favoured for accommodating the substitution of a larger Zn atom.

Journal Article↗

HOLZ line analysis of lattice parameters in magnesium alloys.

A method of refining lattice parameters from deficit higher-order Laue zone (HOLZ) line data from large angle convergent beam electron diffraction (LACBED) data is presented, relying on distances between nearest neighbour intersections alone in order to minimize effects of distortion over the field of view. Use is made of a dynamical correction deltak to the fast electron wavevector k for kinematic analysis. This correction term is shown to depend on the specific HOLZ beam under consideration, as well as the zone axis and eigenvalue associated with the branch index of the relevant dispersion surface. This method is applied to analysis of data from magnesium alloys, where momentum filtering induced by the LACBED method facilitates HOLZ contrast from a relatively low index zone axis (where contrast is not detectable with conventional CBED), and contrast is enhanced at elevated temperatures from a higher index zone axis. Although the accuracy of refined lattice parameters from these sets of data is shown to be no better than 0.1%, it is felt that issues arising out of the analysis may be of some interest, particularly since these are non-ideal specimens. Full eigen-state analysis of the fast electron wavefunction is presented, and issues related to the influence of the dispersion surface on deficit HOLZ line behaviour are discussed.

Journal Article↗

Rapid detection of Mycobacterium bovis on its lipid profile by thin layer chromatography.

Sixteen Mycobacterium bovis (M. bovis) strains isolated from bovine tissues and one standard reference strain of M. bovis AN5 alongwith other species of mycobacteria for comparison were investigated for the presence of phenolic glycolipid (PGL) and phthiocerol dimycocerosate (PDIM) for rapid identification of M. bovis by thin-layer chromatography (TLC). The study indicated presence of PGL with an Rf value of 0.75 in chloroform-methanol solvent in all 17 M. bovis strains. The dimycocerostate A corresponding to spot A was the major constituent among all the three spots in M. bovis strains. TLC appeared to be a promising alternative to conventional biochemical methods for identification of M. bovis taking into consideration both PGL and PDIM lipids.

Animals↗

Excretion of clofazimine in human milk in leprosy patients.

Clofazimine is an important and effective constituent of multi drug therapy for leprosy. A study has been conducted to determine the distribution of clofazimine in maternal milk so that the safety of breast-feeding during maternal ingestion of the drug can be ascertained. Eight female leprosy patients (LL/BL) on clofazimine, 50 mg daily or 100 mg on alternate days for 1-18 months, (mean 5.0 +/- 1.81 months; median 3.25 months) and in the early lactating phase were studied. Blood samples and milk specimens were collected 4-6 hr after the last daily dose. Clofazimine was assayed in the milk and plasma samples by HPTLC. Mean plasma and milk clofazimine levels were 0.9 +/- 0.03 micrograms/ml and 1.33 +/- 0.09 micrograms/ml respectively. The ratio of milk to plasma drug concentration ranged from 1.0 to 1.7 with a mean of 1.48 +/- 0.08. The amount of drug ingested by the infants was 0.199 +/- 0.013 mg/kg/day which represented 22.1 +/- 1.9% of the maternal dose.

Adult↗

Calcification of peripheral nerves in leprosy.

A study conducted in 74 TT/TB patients, with gross thickening of nerves together with nerve abscess, showed calcification in 8 patients. Calcification was most common in the ulnar nerve followed by the lateral popliteal nerve. All eight patients were males with significantly longer duration of illness before start of treatment. Patients with late onset of nerve abscess were found to be more prone to calcium deposition in the nerves. Caseous pus of the abscess had high lipid content with raised cholesterol and cholesterol ester ratio to total lipids suggesting a dystrophic nature of calcification.

Abscess↗

Pharmacokinetic drug interactions with rifampicin.

Rifampicin, an antituberculosis drug, is usually administered for 4 to 12 months with other antituberculosis drugs or medications from other classes. A potential for drug interactions often exists because rifampicin is a potent inducer of hepatic drug metabolism, as evidenced by a proliferation of smooth endoplasmic reticulum and an increase in the cytochrome P450 content in the liver. The induction is a highly selective process and not every drug metabolised via oxidation is affected. Case reports and studies have demonstrated enhanced metabolism of several drugs; most of these interactions are clinically important. At the start of rifampicin treatment, and again at the end, clinicians must check the dosages of any accompanying medications with which rifampicin may potentially interact. Monitoring of clinical response and blood drug concentrations is essential to adjust the drug dosage during rifampicin therapy. Rifampicin also interacts with cholephils such as bilirubin and bromosulphthalein. Its pharmacokinetics are reported to be altered by ethambutol, p-aminosalicylic acid (through its excipient component), ketoconazole, cyclosporin, clofazimine, probenecid and phenobarbital through one or other of the following mechanisms--impaired absorption of rifampicin, competition between the drug and rifampicin for hepatic uptake and altered hepatic metabolism of rifampicin. Most interactions affecting rifampicin have been relatively minor or are not expected to alter its therapeutic efficacy.

Drug Incompatibility↗

Clinical pharmacokinetic considerations in the treatment of patients with leprosy.

On the basis of the efficacy of the available agents, the World Health Organization has recommended only 4 drugs for combined chemotherapy of leprosy: rifampicin, dapsone, clofazimine and ethionamide/prothionamide. Thiacetazone and isoniazid are also used to a lesser extent by some physicians. Pyrazinamide may find a place in treating 'persister' bacilli. Dapsone is absorbed slowly after oral administration. Peak plasma drug concentration is reached at about 4 hours; absorption half-life is 1.1 hours; elimination half-life is about 30 hours. Oral availability is around 90%. Dapsone is approximately 70% protein-bound, while its monoacetylated metabolite is almost entirely bound. Dapsone crosses the placenta and is excreted into breast milk. It is metabolised via acetylation and N-hydroxylation, but acetylation polymorphism has no effect on dapsone handling by leprosy patients. Dapsone penetrates into sciatic nerves of experimental animals but its presence has not been demonstrated in Schwann cells. Oral doses of rifampicin are rapidly and completely absorbed. The bioavailability is greater when the drug is given before meals; peak concentrations occur at 1 to 2 hours. 80 to 90% of rifampicin is bound to plasma proteins, and the drug is found in saliva, cerebrospinal fluid and breast milk. Its main metabolite, desacetyl rifampicin, also exhibits antimycobacterial activity in tuberculosis. Rifampicin induces its own metabolism, as well as that of dapsone and steroids. Absorption of dapsone and rifampicin is reported to be reduced in leprosy patients. Clofazimine has been in use in leprosy treatment since 1960. In higher doses it exerts an anti-inflammatory action which is useful in treating leprosy patients in reaction. Oral absorption of the drug is slow and dose-dependent; faecal excretion also increases with dose. Single- and multiple-dose studies have shown a plasma half-life of around 10 days. Bioavailability of the drug is higher when given with food than when fasting; the peak plasma concentration occurs at 4 to 8 hours when the drug is administered with breakfast. After absorption, the drug is thought to circulate in protein-bound form, accounting for the fact that it is deposited in various tissues. Uneven distribution and prolonged retention in the tissues are special features of clofazimine metabolism. One unconjugated and 2 conjugated metabolites have been detected in urine, and the urinary excretion of both the parent compound and its metabolites is around 1% of the dose.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗

Isolation, purification and quantification of phenolic glycolipid-1 from human leprosy skin tissues.

Phenolic glycolipid-I, a marker lipid of Mycobacterium leprae, was isolated from skin biopsies obtained from untreated lepromatous leprosy patients by silicic acid and florisil column chromatography and purified by thin layer chromatography. Tissues with varying bacillary loads were analysed for their phenolic glycolipid content. A good correlation was observed between the bacillary population of the tissues and the phenolic glycolipid content.

Antigens, Bacterial↗

The effect of clofazimine on the pharmacokinetics of rifampicin and dapsone in leprosy.

Fifteen untreated leprosy patients were given rifampicin and dapsone for seven days, and then rifampicin, dapsone and clofazimine for seven days. Concentrations of rifampicin and dapsone were estimated in timed plasma specimens and in 24 h urine specimens on days 7 and 14. No significant differences in the pharmacokinetics of rifampicin and dapsone were observed between the two occasions of sampling.

Clofazimine↗

Disposition of dapsone in protein deficiency--an experimental study in mice.

With an aim to evaluate the metabolic disposition of Dapsone (DDS) in protein malnutrition, a study was undertaken to determine DDS content of blood and tissues of protein deficient mice in comparison to the levels in ad-libitum and pair-fed mice. Three groups of Rockfeller's strain mice of same sex (roughly weighing 25 gm) were fed on low protein diet and high protein diet (for pair-fed and ad-libitum groups). After one month feeding DDS was administered by oral intubation daily for 7 days at a dose of 0.01 mg per g body weight. On 7th day animals were sacrificed 3 hours after DDS administration. Heparinised blood was collected from ocular plexus. Tissues (liver and kidney) were taken out for DDS estimations. DDS levels were determined by the method of Simpson (1949) and tissue protein content was assayed by the method of Lowry et al (1951). Hypoproteinemic mice presented higher values for blood and tissue DDS as compared to their pair-fed and ad-libitum fed groups. Our observations indicate that in hypoproteinemic mice, on account of the possible diminished binding of DDS to plasma albumin, the concentration of free DDS in blood and in tissues is higher.

Animals↗