Development of cloxacillin loaded multiple-unit alginate-based floating system by emulsion-gelation method

This work investigates the development, optimization and in vitro evaluation of liquid paraffin-entrapped multiple-unit alginate-based floating system containing cloxacillin by emulsion-gelation method for gastro retentive delivery. The effect of process variables like drug to polymer ratio by weight, and liquid paraffin to water ratio by volume on various physicochemical properties in case of liquid paraffin-entrapped calcium alginate beads containing cloxacillin applicable to drug entrapment efficiency, density and drug release was optimized using 3² factorial design and analyzed using response surface methodology. The observed (actual values) responses were coincided well with the predicted values, given by the optimization technique. The optimized beads showed drug entrapment efficiency of 64.63 ± 0.78%, density of 0.90 ± 0.05 g/cm³, and drug release of 56.72 ± 0.85% in simulated gastric fluid (pH 1.2) after 8 h with floating lag time of 8.45 min and floated well over 12 h in simulated gastric fluid (pH 1.2). The average size of all dried beads ranged from 1.73 ± 0.04 to 1.97 ± 0.08 mm. The beads were characterized by SEM and FTIR for surface morphology and excipients-drug interaction analysis, respectively. All these beads showed prolonged sustained release of cloxacillin over 8 h in simulated gastric fluid (pH 1.2). The cloxacillin release profile from liquid paraffin beads followed Korsmeyer-Peppas model over a period of 8 h with anomalous (non-Fickian) diffusion mechanism for drug release.     

An efficient micropropagation protocol for Citrus jambhiri Lush. and assessment of clonal fidelity employing anatomical studies and RAPD markers

Citrus jambhiri (rough lemon) is considered a major rootstock source for a number of Citrus species. A simple method for micropropagation from nodal segments is reported. Nodal segments of C. jambhiri were inoculated on MS medium supplemented with different concentrations and combinations of 6-benzylaminopurine (BAP), kinetin, and N6-(2-isopentenyl) adenosine (2iP). Maximum multiple shoot regeneration response (75?%) was observed with BAP at 3?mg?l^?1. Shoots were multiplied for 30?d on fresh medium with similar composition. A total of 67?% of the cultures showed multiplication with the optimum number of shoots (4.02) and height of shoots (1.81?cm) with BAP (3?mg?l^?1) alone. Maximum rooting response (87?%) was observed with naphthaleneacetic acid at 0.5?mg?l^?1. Transverse sections of shoot stems obtained in vivo (sampled from seedlings) and in vitro (regenerated from nodal segments), showed similar anatomies. Randomly amplified polymorphic DNA analysis confirmed that all the regenerated plants were genetically identical to their donor plant, suggesting absence of detectable genetic variation in the regenerated plantlets.     

Heat injury prevention--a military perspective

Heat-related injuries, and specifically exertional heat stroke, are a significant occupational risk in the armed forces, especially for those soldiers who are rapidly deployed from a temperate climate region to hot climate regions. Traditionally, adaptation to heat was considered as a matter of physiological adaptation. It is clear today that these injuries are mostly avoidable when applying proper education and behavioral adaptations. Education on behavioral adaptation for the prevention of heat injuries should be targeted at the individual and the organization level. This article summarizes the issue of proper preventive measures that should be taken to avoid, or at least minimize, the risk of exertional heat related injuries during military operations and training.     

Anti-cooperative and cooperative protein-protein interactions between TetR isoforms on synthetic enhancers

Protein-protein interactions play an important role in determining the regulatory output of cis regulatory regions. In this work, we revisit the regulatory output functions recorded for the synthetic enhancers that contain binding sites for TetR. We use our thermodynamic model as an analysis tool to infer that two different types of interactions may take place between the TetR molecules. First, a strong mutually exclusive anti-cooperative interaction precludes the synthetic enhancer from being occupied by more than one AT (the aTc bound TetR isoform) protein, and a second weak cooperative interaction exists between the aTc-free TetR isoform (T). Consequently, this work highlights the power of the synthetic enhancer approach as a tool for studying protein-protein interactions via an experimentally verifiable prediction for the general mode of binding of the TetR repressor.     

Disparities in counseling for lifestyle modification among obese adults: insights from the Dallas Heart Study

Clinician counseling is a catalyst for lifestyle modification in obesity. Unfortunately, clinicians do not appropriately counsel all obese patients about lifestyle modification. The extent of disparities in clinician counseling is not well understood. Obese participants (BMI ≥30 kg/m², N = 2097) in the Dallas Heart Study (DHS), a probability‐based sample of Dallas County residents ages 18–65, were surveyed regarding health‐care utilization and lifestyle counseling over the year prior to DHS enrollment. Health‐care utilization and counseling were compared between obese participants across three categories based on the presence of 0, 1, or 2+ of the following cardiovascular (CV) risk factors: hypertension, hypercholesterolemia, or diabetes. Logistic regression modeling was used to determine likelihood of counseling in those with 0 vs. 1+ CV risk factors, stratified by race, adjusting for age, sex, insurance status, and education. Among obese subjects who sought medical care, those with 0 CV risk factors, compared to those with 1 or 2+ CV risk factors, were less likely to report counseling about losing weight (41% vs. 67% vs. 87%, P trend <0.001), dietary changes (44% vs. 71% vs. 85%, P trend <0.001), and physical activity (46% vs. 71% vs. 86%, P trend <0.001). Blacks and Hispanics without CV risk factors had a lower odds of receiving counseling than whites without risk factors on weight loss (adjusted odds ratio (OR), 95% confidence interval (CI) for nonwhites 0.19, [0.13–0.28], whites 0.48, [0.26–0.87]); dietary changes (nonwhites 0.19, [0.13–0.27], whites 0.37, [0.21–0.64]); and physical activity (nonwhites 0.22, [0.16–0.32], whites 0.32, [0.18–0.57]). Lifestyle counseling rates by clinicians are suboptimal among obese patients without CV risk factors, especially blacks and Hispanics. Systematic education about and application of lifestyle interventions could capitalize on opportunities for primary CV risk prevention.     

PlzA is a bifunctional c-di-GMP biosensor that promotes tick and mammalian host-adaptation of Borrelia burgdorferi

In this study, we examined the relationship between c-di-GMP and its only known effector protein, PlzA, in Borrelia burgdorferi during the arthropod and mammalian phases of the enzootic cycle. Using a B. burgdorferi strain expressing a plzA point mutant (plzA-R145D) unable to bind c-di-GMP, we confirmed that the protective function of PlzA in ticks is c-di-GMP-dependent. Unlike ΔplzA spirochetes, which are severely attenuated in mice, the plzA-R145D strain was fully infectious, firmly establishing that PlzA serves a c-di-GMP-independent function in mammals. Contrary to prior reports, loss of PlzA did not affect expression of RpoS or RpoS-dependent genes, which are essential for transmission, mammalian host-adaptation and murine infection. To ascertain the nature of PlzA’s c-di-GMP-independent function(s), we employed infection models using (i) host-adapted mutant spirochetes for needle inoculation of immunocompetent mice and (ii) infection of scid mice with in vitro-grown organisms. Both approaches substantially restored ΔplzA infectivity, suggesting that PlzA enables B. burgdorferi to overcome an early bottleneck to infection. Furthermore, using a Borrelia strain expressing a heterologous, constitutively active diguanylate cyclase, we demonstrate that ‘ectopic’ production of c-di-GMP in mammals abrogates spirochete virulence and interferes with RpoS function at the post-translational level in a PlzA-dependent manner. Structural modeling and SAXS analysis of liganded- and unliganded-PlzA revealed marked conformational changes that underlie its biphasic functionality. This structural plasticity likely enables PlzA to serve as a c-di-GMP biosensor that in its respective liganded and unliganded states promote vector- and host-adaptation by the Lyme disease spirochete.     

Romaine lettuce latex deters feeding of banded cucumber beetle: a vehicle for deployment of biochemical defenses

Latex is widely found among plant species and is known to play a defensive role against certain herbivores. Two romaine lettuce, Lactuca sativa L. (Asteraceae) cultivars, 'Valmaine' (resistant) and 'Tall Guzmaine' (susceptible), were selected to study the potential of latex as a defense mechanism against the banded cucumber beetle, Diabrotica balteata LeConte (Coleoptera: Chrysomelidae). Latex from Valmaine strongly inhibited feeding of adult D. balteata compared to latex from Tall Guzmaine when applied to the surface of artificial diet. Beetles consumed significantly less diet from disks treated with Valmaine latex than they consumed from diet treated with Tall Guzmaine latex, in both choice and no-choice tests. In a choice test involving diet disks treated with Valmaine latex from young leaves vs. disks treated with latex from mature leaves, the beetles consumed significantly less diet treated with latex from young leaves. No significant difference in diet consumption was found between diets treated with latex from young and mature leaves of Tall Guzmaine in choice tests. Three solvents of differing polarity (water, methanol, and methylene chloride) were tested to extract deterrent compounds from latex; Valmaine latex extracted with water:methanol (20:80) strongly inhibited beetle feeding when applied to the surface of artificial diet. In no-choice tests, fewer beetles were observed feeding on diet treated with water:methanol (20:80) extract of Valmaine latex than on diet treated with a similar extract of Tall Guzmaine latex, resulting in significantly less consumption of the diet treated with the Valmaine latex extract. These studies suggest that moderately polar chemicals within latex may account for resistance in Valmaine to D. balteata.     

Preparation and reactions of sugar azides with alkynes: synthesis of sugar triazoles as antitubercular agents

5-azido-5-deoxy-xylo-, ribo-, and arabinofuranoses were prepared by the reaction of the respective 5-O-(methanesulfonyl) or p-toluenesulfonyl derivatives with NaN3 in DMF. The intermediate 5-azido-5-deoxy glycofuranoses on 1,3-cycloaddition with different alkynes in the presence of CuSO4 and sodium ascorbate gave the corresponding sugar triazoles in very good yields. The synthesized sugar triazoles were evaluated for their antitubercular activity against Mycobacterium tuberculosis H37Rv, where one of the compounds displayed mild antitubercular activity in vitro with MIC 12.5 microg/mL.