The reliability of catheter-tip transducers for the measurement of intrauterine pressure in the third stage of labour

In order to assess the reliability of intrauterine pressure measurements in the third stage of labour, catheter-tip transducers were used in 20 women randomly allocated into two groups of 10. In each case in the first group two catheters were tied together and introduced transcervically into the uterine cavity after delivery of the placenta. In each case in the second group two catheters were inserted independently into the same uterine cavity. The active and cumulative active pressures recorded from the pairs of catheters within each uterine cavity were compared. Comparison of individual active pressure readings from separate transducers revealed good agreement whether the catheters were tied together or were seperate. Cumulative active pressure was very similar when assessed by each catheter in the same uterus. Intrauterine catheter-tip transducers can be used reliably to measure uterine activity in the third stage of labour although there may be minor contraction by contraction differences in recordings of individual active pressures.     

Actin Pedestal Formation by Enterohemorrhagic Escherichia coli Enhances Bacterial Host Cell Attachment and Concomitant Type III Translocation

Attachment of enterohemorrhagic Escherichia coli (EHEC) to intestinal epithelial cells is critical for colonization and is associated with localized actin assembly beneath bound bacteria. The formation of these actin “pedestals” is dependent on the translocation of effectors into mammalian cells via a type III secretion system (T3SS). Tir, an effector required for pedestal formation, localizes in the host cell plasma membrane and promotes attachment of bacteria to mammalian cells by binding to the EHEC outer surface protein Intimin. Actin pedestal formation has been shown to foster intestinal colonization by EHEC in some animal models, but the mechanisms responsible for this remain undefined. Investigation of the role of Tir-mediated actin assembly promoting host cell binding is complicated by other, potentially redundant EHEC-encoded binding pathways, so we utilized cell binding assays that specifically detect binding mediated by Tir-Intimin interaction. We also assessed the role of Tir-mediated actin assembly in two-step assays that temporally segregated initial translocation of Tir from subsequent Tir-Intimin interaction, thereby permitting the distinction of effects on translocation from effects on cell attachment. In these experimental systems, we compromised Tir-mediated actin assembly by chemically inhibiting actin assembly or by infecting mammalian cells with EHEC mutants that translocate Tir but are specifically defective in Tir-mediated pedestal formation. We found that an inability of Tir to promote actin assembly resulted in a significant and striking decrease in bacterial binding mediated by Tir and Intimin. Bacterial mutants defective for pedestal formation translocated type III effectors to mammalian cells with reduced efficiency, but the decrease in translocation could be entirely accounted for by the decrease in host cell attachment.     

Blue-emissive two-component supergelator with aggregation-induced enhanced emission

Two-component organogels offer several advantages over one-component gels, but their design is highly challenging. Hence, it is extremely important to design new approaches for the crafting of two-component organogels with interesting optical and mechanical properties. Herein, we report the design of a new class of two-component supergelators obtained from the assembly between acid functionalized tetraphenylethylene (TPE)-based dendrons and alkylated melamine. No gelation behaviour is observed for the individual components, but interestingly, remarkable gelation behaviour is observed for their hydrogen-bonded complex. The primary driving force responsible for the gelation is the strong π–π stacking interaction of TPE units. Because of the strong π-stacking of TPEs in the gel state, the C(sp²)–C(sp²) bond rotation of the TPE segment is completely arrested in the gel state, which results in intense fluorescence emission of the gels. Furthermore, excellent elastic response is observed for the gels as evident from their high storage modulus compared to loss modulus values. Our results clearly demonstrate that by the appropriate selection of the molecular components, this approach can be applied for the creation of functional nanomaterials with emergent properties absent in the individual blocks.

Design of a novel class of two-component, highly emissive, low molecular weight supergelator is reported.     

Potential applications of lactic acid bacteria and bacteriocins in antimycobacterial therapy

Tuberculosis(TB) is a communicable disease caused by Mycobacterium tuberculosis(M. tuberculosis). WHO estimated that 10.4 million new(incident) TB cases worldwide in year 2016. The increased prevalence of drug resistant strains and side effects associated with the current anti-tubercular drugs make the treatment options more complicated. Hence, there are necessities to identify new drug candidates to fight against various sub-populations of M. tuberculosis with less or no toxicity/side effects and shorter treatment duration. Bacteriocins produced by lactic acid bacteria(LAB) attract attention of researchers because of its "Generally recognized as safe" status. LAB and its bacteriocins possess an effective antimicrobial activity against various bacteria and fungi. Interestingly bacteriocins such as nisin and lacticin 3147 have shown antimycobacterial activity in vitro. As probiotics, LAB plays a vital role in promoting various health benefits including ability to modulate immune response against various infectious diseases. LAB and its metabolic products activate immune system and thereby limiting the M. tuberculosis pathogenesis. The protein and peptide engineering techniques paved the ways to obtain hybrid bacteriocin derivatives from the known peptide sequence of existing bacteriocin. In this review, we focus on the antimycobacterial property and immunomodulatory role of LAB and its metabolic products. Techniques for large scale synthesis of potential bacteriocin with multifunctional activity and enhanced stability are also discussed.     

Evidence for an involvement of nitric oxide and gamma aminobutyric acid in the anticonvulsant action of L-arginine on picrotoxin-induced convulsions in rats

Five, 30, and 60 min pretreatment of 1000 mg/kg and not 500 mg/kg of L-arginine inhibited convulsions induced by picrotoxin. The concentrations of nitric oxide (NO) and gamma aminobutyric acid (GABA) were increased in the brain 5, 30, and 60 min after administration of 1000 mg/kg and not 500 mg/kg of L-arginine. A much higher dose of L-arginine (2000 mg/kg), 30 min after administration, produced a lesser anticonvulsant and NO and GABA increasing actions as compared to that produced by 1000 mg/kg of L-arginine. The same dose of L-arginine, 60 min after administration, decreased the concentrations of both NO and GABA and increased the convulsion frequency of picrotoxin. An NO decreasing dose of nitric oxide synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME) decreased brain GABA concentration and increased the convulsant action of picrotoxin. Further, L-NAME pretreatment prevented L-arginine (1000 mg/kg) from producing anticonvulsant and NO and GABA increasing effects. An interpretation of these results suggests that NO synthesized from systemically administered L-arginine inhibits convulsions by increasing the concentration of GABA in the brain. However, the effects of L-arginine are reversible, if it is administered at a higher dose (2000 mg/kg) 60 min prior to the test. It is concluded that L-arginine produces anticonvulsant or proconvulsant action depending upon the dose and time of its administration-related changes in the concentrations of NO and GABA in the brain.     

Evidence for the involvement of L-citrulline but not nitric oxide in the proconvulsant action of the precursor L-arginine on picrotoxin-induced convulsions in rats

To determine the role of the metabolites of L-arginine in its actions on picrotoxin-induced convulsions in rats, the concentrations of nitric oxide (NO) and L-citrulline were measured in the brain 30 and 60 min after the administration of L-arginine (1000 and 2000 mg/kg) or of N-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg), an inhibitor of NO synthase. Animals treated similarly were challenged 30 and 60 min later with picrotoxin (5mg/kg), and the time of onset of myoclonus and clonic convulsions and the frequency of convulsions were determined. These parameters were also determined 30 and 60 min after administering L-arginine in L-NAME-pretreated (30 min) animals. Thirty minutes after the administration of L-arginine, the concentrations of both NO and L-citrulline were raised, the onset of myoclonus and clonic convulsions was delayed, and the frequency of convulsions was decreased, indicating the anticonvulsant property of L-arginine. A 60-min treatment of L-arginine produced a further increase in the concentration of L-citrulline but not that of NO and promoted the frequency of picrotoxin-induced convulsions. Pretreatment with L-NAME prevented L-arginine from raising the concentrations of both NO and L-citrulline; it also promoted the anticonvulsant actions and prevented the proconvulsant actions of L-arginine. These results lead to the conclusion that NO has no involvement in the time-dependent anti and proconvulsant actions of L-arginine on the picrotoxin convulsion model, and that L-citrulline seems to have a role in the proconvulsant action of L-arginine.     

Modulation of fluoride toxicity in rats by calcium carbonate and by withdrawal of fluoride exposure

In order to assess the effect of calcium on the toxic effects of fluoride, adult female Wistar rats were treated with sodium fluoride (NaF, 500 ppm in drinking water) alone or in combination with calcium carbonate (CaCO3, 50 mg/ kg by oral intubation) daily for 60 days. Food, water and fluoride intake were measured daily for 60 days. Body weight gain, exploratory motor activity, rota-rod motor coordination, dental structure, activities of acetylcholinesterase (AchE, brain and skeletal muscle) and Na+ K+ ATPase (erythrocyte membrane and skeletal muscle) and the concentrations of protein (serum and skeletal muscle), calcium (serum) and fluoride (serum) were determined in these animals 24 hr after the last treatment. The same parameters were tested in another group, 60 days after withdrawal of NaF exposure (500 ppm in drinking water daily for 60 days). NaF treatment decreased food and water intake, reduced body-weight gain and impaired exploratory motor activity and rota-rod performance. Dental lesions, inhibition of the activities of AchE and N+ K+ ATPase and a decrease in the concentration of protein, and serum calcium were also observed in these animals. These effects were accompanied by a marked elevation of fluoride concentration in the serum. CaCO3 decreased the concentration of fluoride in the serum of NaF-treated animals. A decrease in serum fluoride concentration was found also after NaF withdrawal. A prevention of locomotor behavioural, biochemical and dental toxicities of fluoride was observed both in these groups. It is concluded that the dose of CaCO3 used in the present study has a potential to prevent the toxicity of fluoride by maintaining serum fluoride at a less toxic level. Further, the toxic effects of fluoride are reversible if its exposure is withdrawn for 2 months.     

Light and ultrastructural study of sciatic nerve lesions induced using intraneural injection of viable Mycobacterium leprae in normal and immunosuppressed Swiss white mice

Freshly harvested M. leprae were microinjected into the sciatic nerves of nonimmunosuppressed (non-TR) and immunosuppressed (TR) mice using the technique described by Wisniewski and Bloom. The lesions thus induced, on bypassing the blood-nerve barrier, were biopsied at regular intervals beginning 24 hr and followed up to one year. The fate of M. leprae and the ensuing inflammation and nerve damage were studied using light and electron microscopy. The lesions in both non-TR and TR mice at 24 hr showed an influx of polymorphonuclear leukocytes and an increase in mast cells. The influx and peaking of lymphocytes were delayed by two weeks and 6 weeks, respectively, in TR mice, but the density of lymphocytes at the peak intervals was comparable in both. The plasma cells denoting the humoral response were seen in both, but there was a delay of 3 weeks in non-TR mice. The lesions in non-TR mice showed differentiation of macrophages into epithelioid cells and the formation of giant cells depicting borderline tuberculoid leprosy (BT), Whereas in TR mice, the macrophages showed foamy cytoplasmic changes depicting borderline lepromatous leprosy (BL). Other significant observations common to both non-TR and TR mice were: a) The lesions remained highly localized and showed signs of regression at the 6th and the 12th month intervals. b) The characteristic segmental demyelination and some attempt at remyelination were seen at the site. c) The influx of lymphocytes concorded well with demyelination. d) Bacteria were only seen in the macrophages and never in the Schwann cells or endothelial cells. e) Bacteria persisted in the macrophages, but appeared progressively degenerate at the 6th and 12th post-inoculation months, suggesting loss of viability. The study shows that there was a very effective containment of the infection and that the Schwann cells were resistant to M. leprae infection in the neural milieu. Nerve damage and Schwann cell bacillation do not go hand-in-hand.     

Preparation of 99mTc-ethylene dicysteine (99mTc-EC) by transchelation using 99mTc-glucoheptonate (99mTc-GHA) and its evaluation for renal function studies

The complexation of ethylene dicysteine (EC) with 99mTc needs to be carried out at pH 12 to achieve a high radiochemical yield. However, the preparation of the kit at high pH poses difficulties and requires very stringent preparation conditions, as stannous tin, one of the main ingredients in the kit, is unstable at high pH. Hence, an alternative method, involving the transchelation preparation of 99mTc-EC using 99mTc-glucoheptonate (99mTc-GHA) prepared at pH 6.5, was attempted, prompted by the reported success of the preparation of 99mTc-sestamibi (99mTc-MIBI) by this method. The preparation of 99mTc-EC by this method first involved the formation of 99mTc-GHA by the addition of sodium pertechnetate-99mTc to the Sn-GHA kit vial at pH 6.5. 99mTc-EC was formed by the addition of reconstituted EC solution at pH approximately 12 to the preformed 99mTc-GHA. The reaction was allowed to proceed both at room temperature and on a boiling water bath. The pH of the final product was adjusted to pH approximately 7 with 0.5 M phosphate buffer at pH 4-5, without affecting the quality of the product. The urinary excretion of 99mTc-EC prepared by transchelation, tested in mice, was similar to that of directly prepared 99mTc-EC, indicating that the final product prepared by the two methods was the same. The clinical evaluation of the product formulated by the new procedure showed satisfactory findings, comparable with the reports in the literature.