Altered anxiety and weight gain in corticotropin-releasing hormone-binding protein-deficient mice

Corticotropin-releasing hormone (CRH) is widely recognized as the primary mediator of the neuroendocrine and behavioral responses to stress, including stress-induced anxiety. The biological activity of CRH and other mammalian CRH-like peptides, such as urocortin, may be modulated by CRH-binding protein (CRH-BP). To assess directly the CRH-BP function, we created a mouse model of CRH-BP deficiency by gene targeting. Basal adrenocorticotropic hormone and corticosterone levels are unchanged in the CRH-BP-deficient mice, and the animals demonstrate a normal increase in adrenocorticotropic hormone and corticosterone after restraint stress. In contrast, adult male CRH-BP-deficient mice show significantly reduced body weight when compared with wild-type controls. CRH-BP-deficient mice also exhibit a significant increase in anxiogenic-like behavior as assessed by the elevated plus maze and defensive withdrawal tests. The increased anorectic and anxiogenic-like behavior most likely is caused by increased "free" CRH and/or urocortin levels in the brain of CRH-BP-deficient animals, suggesting an important role for CRH-BP in maintaining appropriate levels of these peptides in the central nervous system.     

Synthesis of water-soluble and bio-taggable CdSe@ZnS quantum dots

Many synthesized semiconductor QDs materials are formed using trioctylphosphine oxide (TOPO) but it requires high temperature, is very expensive and is also hydrophobic. Our study deals with selective syntheses of CdSe and core–shell CdSe/ZnS quantum dots (QDs) in aqueous solution by a simple heating and refluxing method. It is more hydrophilic, needs less temperature, is economically viable and is eco-friendly. Bio-ligands, such as thioacetamide, itaconic acid and glutathione, were used as stabilizers for the biosynthesis of QDs. A simplified aqueous route was used to improve the quality of the colloidal nanocrystals. As a result, highly monodisperse, photoluminescent and biocompatible nanoparticles were obtained. The synthesized QDs were characterized by XRD, FTIR, confocal microscopy, ultraviolet (UV) absorption and photoluminescence (PL). The size of synthesized QDs was observed as 5.74 nm and the core–shell shape was confirmed by using XRD and confocal microscopy respectively. The QD nanoparticles showed antibacterial activity against pathogenic bacteria. The QDs could be applied for biological labelling, fluorescence bio-sensing and bio-imaging etc.

Mystristic capped CdSe QDs with schematic diagram and formation mechanism of bio-taggable CdSe@ZnS QDs.     

Cardiovascular magnetic resonance left ventricular strain in end-stage renal disease patients after kidney transplantation

Background

Cardiovascular disease is a significant cause of morbidity and mortality in patients with end-stage renal disease (ESRD) and kidney transplant (KT) patients. Compared with left ventricular (LV) ejection fraction (LVEF), LV strain has emerged as an important marker of LV function as it is less load dependent. We sought to evaluate changes in LV strain using cardiovascular magnetic resonance imaging (CMR) in ESRD patients who received KT, to determine whether KT may improve LV function.

Methods

We conducted a prospective multi-centre longitudinal study of 79 ESRD patients (40 on dialysis, 39 underwent KT). CMR was performed at baseline and at 12?months after KT.

Results

Among 79 participants (mean age 55 years; 30% women), KT patients had significant improvement in global circumferential strain (GCS) (p?=?0.007) and global radial strain (GRS) (p?=?0.003), but a decline in global longitudinal strain (GLS) over 12?months (p?=?0.026), while no significant change in any LV strain was observed in the ongoing dialysis group. For KT patients, the improvement in LV strain paralleled improvement in LVEF (57.4?±?6.4% at baseline, 60.6%?±?6.9% at 12?months; p?=?0.001). For entire cohort, over 12?months, change in LVEF was significantly correlated with change in GCS (Spearman’s r?=???0.42, p?<?0.001), GRS (Spearman’s r?=?0.64, p?<?0.001), and GLS (Spearman’s r?=???0.34, p?=?0.002). Improvements in GCS and GRS over 12?months were significantly correlated with reductions in LV end-diastolic volume index and LV end-systolic volume index (all p?<?0.05), but not with change in blood pressure (all p?>?0.10).

Conclusions

Compared with continuation of dialysis, KT was associated with significant improvements in LV strain metrics of GCS and GRS after 12?months, which did not correlate with blood pressure change. This supports the notion that KT has favorable effects on LV function beyond volume and blood pessure control. Larger studies with longer follow-up are needed to confirm these findings.

     

Understanding the sex disparity in living kidney donation

Living donors are the preferred source of organs for kidney transplantation, which is the treatment modality of choice for end‐stage kidney disease. Health care systems widely promote living kidney donation. However, women are consistently overrepresented among living donors. The reasons behind the sex‐based disparity in living kidney donation remain poorly understood. Compared to women, men possess a greater amount of kidney function, and the higher deceased donation rate among men reflects their higher overall kidney quality. A plausible medical explanation for the sex‐based disparity in living kidney donation includes an uncompromising emphasis on preserving donor health, with less emphasis placed on organ quality, which is the main criterion in deceased donor selection. On the other hand, consent to deceased donation is also greater in women, indicating their greater desire to donate even though fewer women actually become deceased donors. Therefore, nonmedical reasons for the sex disparity in living donation must be sought. Increased empathic distress or emotional memory; a greater sense of responsibility, urgency, and impulsiveness with increased reaction to empathy; a different body image; and a different social status may all contribute to greater living kidney donation in women. Economic inequity may be the singular explanation when personal worth links to economic worth. To better understand the sex disparity in living kidney donation, we need better data on the reasons behind both nondonation and donor rejection after evaluation in clinical practice. Nondirected living kidney donation provides unique opportunities to minimize factors such as emotional distress, empathy, and impulsiveness. More liberal acceptance criteria for donors with isolated medical abnormalities and testing legitimate donor reimbursement strategies based on actual income levels rather than a fixed amount can assist in both ascertaining the reasons behind the sex disparity in living kidney donation and increasing overall living kidney donation rates.     

Frequency of Heterotic Hybrids in Relation to Parental Genetic Divergence and General Combining Ability in Dolichos Bean

Though F₁ hybrids are not the immediate cultivar option, development of heterotic F₁ hybrids is relevant from view point of deriving pure lines, the only cultivar choice in dolichos bean, a predominantly self-pollinated grain legume crop species. Heterotic F₁ generates a high frequency of productive derivatives in F₃ and later generations as compared to non-heterotic F₁. The criteria such as combining ability and genetic diversity between parents are being commonly used to develop heterotic hybrids. In this context, an investigation was carried out at University of Agricultural Sciences, Bengaluru, India, to test the predictability of frequency of heterotic hybrids based on parental gca effects and genetic diversity in dolichos bean. The 48 F₁ hybrids generated by crossing 12 lines and 4 testers were evaluated along with their parents for 6 quantitative characters. The overall gca status (high and low) of each parent and overall sca and heterotic status (high and low) of each hybrid for 6 characters were determined. Based on overall gca status and genetic divergence of parents, the hybrids were grouped into different classes. The hybrids involving parents contrasting for overall gca status and/or those involving parents with intermediate genetic divergence were more frequently heterotic than those involving comparable gca status with extreme genetic divergence. Thus, there exists a limit to parental divergence for the occurrence of heterosis. It is hence, desirable to involve parents with intermediate genetic divergence and contrasting gca effects to recover higher frequencies of heterotic hybrids for economic traits in dolichos bean.     

In vitro Antibacterial Activity of Aqueous and Ethanol Extracts of Aristolochia indica and Toddalia asiatica Against Multidrug-Resistant Bacteria

Bacteria have developed multidrug resistance against available antimicrobial agents. Infectious diseases caused by these multidrug-resistant bacteria are major causes of morbidity and mortality in human beings. Synthetic drugs are expensive and inadequate for the treatment of diseases, causing side effects and ineffective against multidrug-resistant bacteria. The medicinal plants are promising to have effective antimicrobial property due to presence of phytochemical compounds like alkaloids, flavanoids, tannins and phenolic compounds. The present study aimed to find the antimicrobial activity of medicinal plants against multidrug-resistant bacteria. Multidrug-resistant bacteria were identified by Kirby-Bauer disc diffusion method. Production of β-lactamases (extended spectrum β-lactamases, metallo β-lactamase and AmpC β-lactamase) were identified by combination disc method. Antibacterial activity of aqueous and ethanol extract of Aristolochia indica and Toddalia asiatica were detected by agar well diffusion assay and minimum inhibitory concentration. All bacteria used in this study showed antibiotic resistance to ≥3 antibiotics. Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis and Vibrio cholerae were found to be positive for β-lactamase production. Ethanol extract of Aristolochia indica showed more significant antibacterial activity against multidrug-resistant bacteria than Toddalia asiatica. Ethanol extracts of Aristolochia indica and Toddalia asiatica showed minimum inhibitory concentration values of 50-100 μg/ml and 100-200 μg/ml, respectively against multidrug-resistant bacteria. From this study, it was concluded that Aristolochia indica has more potential to treat multidrug-resistant bacteria than Toddalia asiatica.     

A Competent and Commercially Viable Process for the Synthesis of the Anti-Hypertensive Drug Olmesartan Medoxomil

Drug product purity and potency are of most significance in the regulatory market as we notice many recalled batches worldwide, particularly in the US and Japan. Olmesartan Medoxomil is an anti-hypertensive drug. The present invention relates to a process for the preparation of Olmesartan Medoxomil with 99.9% purity in an overall 62% yield. The synthesis includes three isolations and one purification with easy plant operations. This process describes the formation and control of each individual impurity in all stages. This process for Olmesartan Medoxomil and its intermediates is competent for industrial production in very short reaction time intervals with an appreciable yield and high purity.