Stable isotope labeling as a promising tool for rapid drug susceptibility testing in Neisseria gonorrhoeae.

The world is heading towards an era of intractable and impending untreatable N. gonorrhoeae, thereby underlining the significance of rapid and accurate prediction of drug resistance as an indispensable need of the hour. In the present study, we optimized and evaluated a stable isotope labeling-based approach using the MALDI-TOF MS (Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry) for rapid and reliable detection of ciprofloxacin and azithromycin resistance in N. gonorrhoeae. All the isolates were cultured under three varied condition setups viz. medium supplemented with normal lysine, heavy lysine (isotope), and heavy lysine along with the antibiotics (ciprofloxacin/azithromycin), respectively. After incubation, spectra were acquired using the MALDI-TOF MS which were further screened for unique patterns (media-specific spectra) to differentiate drug-susceptible and resistant isolates. The results of the stable isotope labeling assay were comparable to the results of phenotypic methods used for susceptibility testing.

Biosynthesis and characterization of gold nanoparticles: Kinetics, in vitro and in vivo study.

This study reports a facile, cost effective, nontoxic and eco-friendly method for the synthesis of gold nanoparticles. In this paper, leaf extract of Mentha piperita was successfully used to reduce chloroauric acid, leading to synthesis of gold nanoparticles (AuNPs). The synthesized nanoparticles were further characterized by UV-visible spectroscopy, Fourier transform infrared spectroscopy, dynamic light scattering, transmission electron microscopy and field emission scanning electron microscopy. Kinetics studies like effect of volume of leaf extract, precursor, pH, temperature for the synthesis of AuNPs were studied spectrophotometrically. Synthesized AuNPs were found to possess hexagon structure where size of nanoparticles was ~78nm in diameter. These biologically synthesized AuNPs exhibited significant activity against cancerous cell lines MDA-MB-231 and A549 and was compared with the normal 3T3-L1 cell line. Anti-inflammatory and analgesic activities were studied on a Wistar rat model to gauge the impact of AuNPs for a probable role in these applications. AuNPs gave positive results for both these activities, although the potency was less as compared to the standard drugs. These results suggested that the leaves extract of Mentha piperita is a very good bioreductant for the synthesis of AuNPs and have potential for various biomedical and pharmaceutical applications.

A review on therapeutic potential of Lygodium flexuosum Linn.

From the centuries, herbal medicines are used to treat various diseases and now they had become an item of global importance, with both medicinal and economic implications. The demand of herbal medicine is being increasing day by day due to their safety and efficacy. Now herbals had taken over the allopathic system due to their less side effect and efficient working mechanism. Herbals are playing and pivotal role in increasing the economy of the country and had taken the nation on to the new path to achieve the goal of development. Lygodium flexuosum (Linn) Sw. is a fern found nearly throughout India up to an elevation of 1500 meter. It belongs to the family Lygodiaceae and widely used in treating various ailments like jaundice, dysmenorrhea, wound healing and eczema. It is the rich source of alkaloids, flavonoids, saponins and cumarin. The main constitute of the plant is lygodinolide which is mainly used in wound healing. In the present review an attempt had been made to explore different aspects of L. flexuosum.

Antitussive activity of Abies webbiana Lindl. leaf extract against sulphur dioxide-induced cough reflex in mice.

The methanol extract of A. webbiana Lindl was evaluated for its effect on a cough model induced by sulphur dioxide gas in mice. When administered orally it exhibited significant antitussive activity compared with the control in a dose dependent manner. The antitussive activity of the extract was compared with that of codeine phosphate, a prototype antitussive agent. The A. webbiana leaf extract (400 and 600 mg/kg) showed maximum inhibition of cough frequency by 71.69% and 78.67%, respectively, when compared with the control group and was comparable in effect to codeine phosphate.

Effect of hypervitaminosis A on intestinal digestive & absorptive functions in rat.

Oral administration of large doses of retinol to young rats significantly accelerated glucose and galactose uptake in small intestinal segments. It also augmented both total and specific activities of brush border membrane associated disaccharidases and blood glucose level. For this investigation the intestine was examined in three segments viz., proximal, mid and distal portion and also as a whole. In comparison with matched controls, total enzymic activities in with hypervitaminosis A animals were nearly double for lactase, sucrase and maltase in all segments. With specific enzymic activities, the change in enzymic activities were greater for lactase and maltase, but less for sucrase.

HIV-1 protease inhibitors: synthesis and biological evaluation of glycopeptidemimetics.

A series of glycopeptidemimetics based on the hydroxyethylene Phe-Phe isostere have been synthesized and evaluated for their ability to inhibit the enzyme HIV-1 protease. Incorporation of carbohydrate moieties at the P'2-position and elimination of P'3 amino acid in our lead compound 1, provided inhibitors with only nanomolar potencies (400-800 nM). However, incorporation of a carbohydrate moiety at the P'3-position with branched chain amino acid at the P'2-position, resulted in inhibitors with subnanomolar potencies. Within this series, compound 21 was the most potent inhibitor (IC50 value 0.17 nM). This compound has also shown to block the spread of HIV-1 in T-lymphoid cells at an inhibitor concentration of 200 nM.

The bioenergetics of preservation of limbs before replantation. The rationale for intermediate hypothermia.

Of all tissues of the extremities, muscle is the least tolerant of ischemia. Hypothermia of tissue is considered beneficial for the maintenance of viability of muscle in amputated limbs before surgical replantation, but it has never been established that conventional cooling in an ice bath or its equivalent (temperature of tissue, approximately 1 degree Celsius) is the optimum level of hypothermia for minimizing metabolic derangement in ischemic muscle. In this study, we first defined the time course and level of metabolic derangement of muscle in twenty-eight ischemic hind limbs in cats at 22, 15, 10, 5, and 1 degree Celsius. The levels of adenosine triphosphate and phosphocreatine and the mean intracellular pH of the muscles in the lateral aspect of the thigh in each limb were monitored with phosphorus nuclear magnetic-resonance spectroscopy over time. The excised muscles from six freshly amputated legs of live humans were then similarly studied to determine whether muscles from cats and from humans exhibit comparable bioenergetic responses to hypothermic ischemia. A final series of ten ischemic hind limbs from cats was studied by nuclear magnetic resonance and muscle biopsy for direct biochemical assay of tissue energy metabolites to compare the metabolic benefits of two different methods of preserving limbs: continuous cooling in an ice bath, and a newly devised protocol for the rapid induction and maintenance of so-called intermediate (10 +/- 5 degrees Celsius) hypothermia of tissue. Ischemic skeletal muscle in cats exhibited a paradoxical metabolic response to extreme cold (1 degree Celsius). The rate of metabolic deterioration progressively declined with decreasing temperature of tissue to 10 degrees Celsius. However, at 5 degrees Celsius, no additional benefit was detected, and at 1 degree Celsius, there was a significant acceleration in the rates of degradation of adenosine triphosphate and phosphocreatine and in the production of lactate. The rate of degradation of adenosine triphosphate in human ischemic muscle was also faster at 1 degree Celsius than at 10 degrees Celsius. This paradoxical response is apparently due to a severe inhibition of the calcium pump of the sarcoplasmic reticulum of the muscle cell at temperatures of less than 5 degrees Celsius. The inhibition permits an efflux of calcium to the myofibrils, which stimulates both glycolysis and the degradation of adenosine triphosphate by myofibrillar adenosine triphosphatase.

Leishmania donovani: amastigote inhibition and mode of action of berberine.

Berberine, an alkaloid from Berberis aristata Linnaeus, may be a useful drug for the treatment of visceral leishmaniasis. In both the 8-day and long-term models of Leishmania donovani infection in hamsters, it markedly diminished the parasitic load and proved to be less toxic than pentamidine. It rapidly improved the hematological picture of infected animals. Like pentamidine, it inhibited in vitro multiplication of amastigotes in macrophage culture and their transformation to promastigotes in cell free culture. Manometric studies showed that both drugs had inhibitory action on both the endogenous and the glucose-stimulated respiration of amastigotes. They inhibited incorporation of [14C]adenine, [14C]uracil, and [3H]thymidine into nucleic acids, and of [14C]leucine into the protein of amastigotes, indicating an inhibitory action on macromolecular biosynthesis. They also decreased deoxyglucose uptake. Using spectrophotometric, spectrofluorimetric, and circular dichroism techniques, berberine was found to interact in vitro with nuclear DNA from L. donovani promastigotes.

Hemagglutinating activity in extracts of mycelia from submerged mushroom cultures.

Extracts from mycelia of seven different mushrooms agglutinated erythrocytes of several species. More than one agglutinating factor was identified in the extracts of three different mycelia. Agglutination was partially inhibited nonspecifically by high concentrations of glucose, galactose, mannose, fucose, and rhamnose.

Cryosurgery of genital warts in cases in which podophyllin treatment failed or was contraindicated.

A total of 56 cases with warts in which podophyllin treatment was either contraindicated or a failure, were treated with nitrous oxide using a Keymed 500 cryosurgical appliance. Forty-three patients who completed treatment were followed-up for three months. Thirty-seven of these had received applications of podophyllin twice weekly for an average period of three months before cryosurgery. The remaining cases in whom podophyllin was considered to be contraindicated included five with vulval warts (two were pregnant, two were bronchial asthmatics taking oral prednisolone, and one was taking oral clomiphene citrate), and a diabetic patients with penile warts. Thirty-two were cured and 11 relapsed. The latter were re-treated at the end of the follow-up period with two freezing cycles of 45 seconds at an interval of 30 minutes. Seven were cured and the remaining four men who failed to respond belonged to the podophyllin-resistant group and included three with metal warts and one homosexual with anogenital warts. Cryosurgery gave a cumulative success rate of 91%. A single freezing cycle was free from complications but a double freezing cycle was often followed by severe local reaction.