Geochemical evaluation, ecological and human health risk assessment of potentially toxic elements in urban soil, Southern India.

Roadside soil contamination is mostly caused by human-caused pollutant deposition. PTEs are among the many substances that are harmful for both humans and the environment. PTE concentrations in roadside soil in Chennai, southern India, have been determined in this study. To evaluate the seriousness of the threats, more environmental and geochemical indices have been applied. 83 soil samples have been obtained from the study regions and focusing on important roads. Elemental analysis has been analyzed with ED-XRF and sieve-filtered samples focused on PTEs such as arsenic, barium, cobalt, chromium, copper, iron, potassium, nickel, lead, thorium, titanium, zinc, and uranium. Significant metallic variations have been found in soil samples around roads by the investigation. The elements this study examined section ascending in the following sequence: Fe > Ti > Zn > Cr > Pb > Cu > Ni > Th > As > U > K. In the research area, the CD classification denotes high contamination, whereas the CF indices show mild to significant pollution. PLI indicates moderate to high pollution, whereas EF suggests excessive enrichment. Igeo demonstrates a range from uncontaminated to highly contaminated. PERI showed high levels in the northern study region, whereas GUFI shows several hot spots indicating moderate to severe pollution. The Hazard Index (HI) values for all metals were less than one, demonstrating the absence of non-carcinogenic risks for both adults and children. Multivariate data show natural and anthropogenic PTEs in roadside soil. In addition, a soil quality monitoring system is needed to mitigate continual contamination risks.

Optimization of Ultrasound-Assisted Microwave Encapsulation of Peanut Oil in Protein-Polysaccharide Complex.

Research background: Peanut oil (Arachis hypogaea L.) is a rich source of unsaturated fatty acids. Its consumption has been reported to have biological effects on human health. Unsaturated, especially polyunsaturated fatty acids (PUFA) found in peanut oil are highly susceptible to oxidation, leading to the formation of harmful compounds during processing and storage. The aim of this study is to prevent the oxidation of peanut oil PUFA by encapsulation in a protein-polysaccharide complex using microwave drying. Experimental approach: The combined effect of corn starch (CS) and whey protein isolate (WPI) was evaluated for ultrasound-assisted microwave encapsulation of peanut oil to prevent oxidative degradation. The effect of independent parameters, viz. CS:WPI mass ratio (1:1 to 5:1), lecithin mass fraction (0-5 %), ultrasonication time (0-10 min) and microwave power (150-750 W) on the encapsulation of peanut oil was evaluated using response surface methodology (RSM). The process responses, viz. viscosity and stability of the emulsion, encapsulation efficiency, peroxide value, antioxidant activity, free fatty acids (FFA), moisture, angle of repose and flowability (Hausner ratio (HR) and Carr's Index (CI)) were recorded and analysed to optimize the independent variables. Results and conclusions: The viscosity of all emulsions prepared for encapsulation by ultrasonication ranged from 0.0069 to 0.0144 Pa·s and more than 90 % of prepared combinations were stable over 7 days. The observed encapsulation efficiency of peanut oil was 21.82-74.25 %. The encapsulation efficiency was significantly affected by the CS:WPI mass ratio and ultrasonication. The peroxide value, antioxidant activity and FFA ranged from 1.789 to 3.723 mg/kg oil, 19.81-72.62 % and 0.042-0.127 %, respectively. Physical properties such as moisture content, angle of repose, HR and CI were 1.94-8.70 %, 46.5-58.3°, 1.117-1.246 and 10.48-22.14 %, respectively. The physical properties were significantly affected by surface properties of the capsules. The higher efficiency (74.25 %) of peanut oil encapsulation was achieved under optimised conditions of CS:WPI mass ratio 1.25, 0.25 % lecithin, 9.99 min ultrasonication and 355.41 W microwave power. Novelty and scientific contribution: The results of this work contribute to the fields of food science and technology by providing a practical approach to preserving the nutritional quality of peanut oil and improving its stability through encapsulation, thereby promoting its potential health benefits to consumers and applications in various industries such as dairy and bakery.

GLYCOSYLATED FIBRONECTIN AND INHIBIN ARE LOWER AND ANTI-MÜLLERIAN HORMONE IS HIGHER IN UMBILICAL CORD BLOOD WHEN MOTHERS HAVE PREECLAMPSIA.

Objective: Preeclampsia is a common disorder of pregnancy, causing significant morbidity and mortality for mothers and infants. Several molecules, including glycosylated fibronectin (GlyFn), the inhibin-related proteins, anti-müllerian hormone (AMH), and the insulin-like growth factor axis, are altered in maternal plasma in the setting of preeclampsia; however, these molecules have not been previously measured in cord blood of infants born to mothers with preeclampsia, which may represent changes in fetal physiology. We evaluated potential biomarkers of preeclampsia in umbilical cord blood to fill the gap in knowledge. Methods: This is a case-control study of 196 neonates born at a tertiary teaching hospital in Boston from 2010-2017. Forty-nine neonates born to mothers with preeclampsia were matched 1:3 by gestational age, sex, and birth weight z-score with 147 controls. Eleven analytes were measured in cord blood by enzyme-linked immunosorbent assay. Binary logistic regression analyses were performed to evaluate associations between preeclampsia and analytes. Results: Mean cord blood levels of GlyFn and total inhibin were significantly lower in neonates born to mothers with preeclampsia compared to controls, and AMH levels were significantly higher in males born to mothers with preeclampsia than male controls. Associations remained significant after controlling for maternal and neonatal characteristics. Conclusion: Cord blood levels of GlyFn and inhibin are decreased and AMH (male) levels are increased in infants of preeclamptic mothers, which is opposite the pattern these biomarkers show in serum of mothers with preeclampsia. These molecules may be important in the pathophysiology and long-term effects of preeclampsia on the developing fetus. Abbreviations: AMH = anti-müllerian hormone; ELISA = enzyme-linked immunosorbent assay; GlyFn = glycosylated fibronectin; IGF = insulin-like growth factor; IGFBP5 = insulin-like growth factor binding protein 5; LOD = limit of detection; PAPP-A = pregnancy-associated plasma protein A; PAPP-A2 = pregnancy-associated plasma protein A2.

Asthma control and asthma treatment adherence in primary care: results from the prospective, multicentre, non-interventional, observational cohort ASCOPE study in Malaysia.

INTRODUCTION: As the first point of contact for those presenting with asthma symptoms, primary healthcare plays a crucial role in asthma management. This is a nationwide study of assessment of asthma symptom control and adherence to asthma medication among outpatients in public health clinics in Malaysia. METHODS: This is a prospective, observational multicentre study (ASCOPE; NCT03804632). Data on asthma control, assessment of control symptoms, and adherence to treatment were collected from medical records and interviews of patients. The level of asthma control was assessed using the Global Initiative for Asthma (GINA) Assessment of Symptom Control. Adherence of patient to medication for asthma was assessed through interview of patients using four questions adapted from the Malaysian Medication Adherence Scale. RESULTS: Among the 1011 patients recruited, 416 (41%) had well controlled asthma, 388 (38%) were partly controlled, and 207 (21%) had uncontrolled asthma. Majority (81%) had mild asthma and all patients were on asthma medication. Most patients did not have spirometry data (97%) but underwent peak flow rate measurements (98%). Poor adherence occurred at all levels of asthma control but was worst among those with uncontrolled asthma. This was statistically significant across all four questions on adherence (p<0.05). For example, more patients with uncontrolled asthma forgot doses (56%) or stopped treatment (39%) than those with well-controlled asthma (44% and 27%respectively). CONCLUSIONS: Among Malaysian primary care patients with asthma, less than 50% had well-controlled asthma, and low adherence to treatment was common. More effort is needed to improve asthma control among patients in Malaysia, including those with mild asthma.

Multi-energy spectral CT: adding value in emergency body imaging.

Most vendors offer scanners capable of dual- or multi-energy computed tomography (CT) imaging. Advantages of multi-energy CT scanning include superior tissue characterization, detection of subtle iodine uptake differences, and opportunities to reduce contrast dose. However, utilization of this technology in the emergency department (ED) remains low. The purpose of this pictorial essay is to illustrate the value of multi-energy CT scanning in emergency body imaging.

Hydrogen sulfide depletion contributes to microvascular remodeling in obesity.

Structural remodeling of the microvasculature occurs during obesity. Based on observations that impaired H2S signaling is associated with cardiovascular pathologies, the current study was designed to test the hypothesis that altered H2S homeostasis is involved in driving the remodeling process in a diet-induced mouse model of obesity. The structural and passive mechanical properties of mesenteric resistance arterioles isolated from 30-wk-old lean and obese mice were assessed using pressure myography, and vessel H2S levels were quantified using the H2S indicator sulfidefluor 7-AM. Remodeling gene expression was assessed using quantitative RT-PCR, and histological staining was used to quantify vessel collagen and elastin. Obesity was found to be associated with decreased vessel H2S concentration, inward hypertrophic remodeling, altered collagen-to-elastin ratio, and reduced vessel stiffness. In addition, mRNA levels of fibronectin, collagen types I and III, matrix metalloproteinases 2 and 9, and tissue inhibitor of metalloproteinase 1 were increased and elastin was decreased by obesity. Evidence that decreased H2S was responsible for the genetic changes was provided by experiments in which H2S levels were manipulated, either by inhibition of the H2S-generating enzyme cystathionine γ-lyase with dl-propargylglycine or by incubation with the H2S donor GYY4137. These data suggest that, during obesity, depletion of H2S is involved in orchestrating the genetic changes underpinning inward hypertrophic remodeling in the microvasculature.

Wound healing activities of PVA-urea composites from Ormocarpum cochinchinense.

The aim of this work is to prepare ternary blended polyvinyl alcohol (PVA)-urea hydrogels containing Ormocarpum cochinchinense, Cinnamomum zeylanicum and antibiotic cephalexin by freezing-thawing method in order to assess the wound healing qualities. In addition to being a synthetic polymer, PVA is a recyclable and biocompatible artificial polymer blend that has attracted a lot of interest in biological applications. The freezing-thawing process with PVA-urea blend is used to make hydrogel film. Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM) and swelling investigations were carried out for the composite membranes. Biological studies involving antibacterial, antifungal, cytotoxicity and wound healing activities were also carried out for the composite membranes. The composite membrane developed has a lot of potential for wound dressing and other applications.

The role of mitochondrial uncoupling in the regulation of mitostasis after traumatic brain injury.

Mitostasis, the maintenance of healthy mitochondria, plays a critical role in brain health. The brain's high energy demands and reliance on mitochondria for energy production make mitostasis vital for neuronal function. Traumatic brain injury (TBI) disrupts mitochondrial homeostasis, leading to secondary cellular damage, neuronal degeneration, and cognitive deficits. Mild mitochondrial uncoupling, which dissociates ATP production from oxygen consumption, offers a promising avenue for TBI treatment. Accumulating evidence, from endogenous and exogenous mitochondrial uncoupling, suggests that mitostasis is closely regulating by mitochondrial uncoupling and cellular injury environments may be more sensitive to uncoupling. Mitochondrial uncoupling can mitigate calcium overload, reduce oxidative stress, and induce mitochondrial proteostasis and mitophagy, a process that eliminates damaged mitochondria. The interplay between mitochondrial uncoupling and mitostasis is ripe for further investigation in the context of TBI. These multi-faceted mechanisms of action for mitochondrial uncoupling hold promise for TBI therapy, with the potential to restore mitochondrial health, improve neurological outcomes, and prevent long-term TBI-related pathology.

An in vitro comparison of antimicrobial effcacy of three root canal irrigants-BioPure MTAD, 2% chlorhexidine gluconate and 5.25% sodium hypochlorite as a final rinse against E. faecalis.

AIM: This study was conducted to evaluate the antimicrobial activity of 5.25% sodium hypochlorite (NaOCl), 2% chlorhexidine (CHX) and BioPure MTAD when used as a fnal rinse against Enterococcus faecalis. MATERIALS AND METHODS: Sixty single-rooted premolars were biomechanically prepared, inoculated with E. faecalis and divided into various groups. These were then irrigated with the test irrigants and tested microbiologically for growth of E. faecalis immediately after irrigation and after 48 hours. RESULTS: Statistical analysis showed that there was a signifcant difference between the antibacterial activities of BioPure MTAD, 2% CHX and 5.25% NaOCl at 5 minutes; however, the antibacterial activities of the three irrigants were comparable after 2 days of irrigation. CONCLUSION: The present study concludes that BioPure MTAD is as effective against E. faecalis as 5.25% NaOCl and more effective than 2% CHX. CLINICAL SIGNIFCANCE: E. faecalis is one of the most resistant intracanal species and a possible cause of root canal failure. Many authors have stressed the importance of using antimicrobial irrigants during chemomechanical preparation to ensure complete disinfection. Therefore, various irrigating solutions have been used during and immediately after root canal preparation to remove debris and necrotic pulp tissue and to eliminate microorganisms that cannot be reached by mechanical instrumentation.

Aging Skin and Natural Bioactives that Impede Cutaneous Aging: A Narrative Review.

The skin aging which entails modifications in the entire skin and skin support system is caused as a result of complex blend of intrinsic and extrinsic factors. The main objective of this review is to provide critical insights into the effect of the aging determinants (intrinsic and extrinsic) on aging skin and to focus on a few classes of natural bioactives that were reported to counteract symptoms of cutaneous aging, pose potential, and beneficial health effect on aging skin supported with relevant scientific evidence. The narrative review of this cutaneous antiaging study incorporating the literature findings was retrieved from the search of computerized databases PubMed and Scopus, hand searches, and authoritative books. The antiaging skin care approach of using bioactives are basically nutritional hormetins, available from our natural heritage, identified as potent free radical scavengers, antioxidants, moisturizers, cell repairing agents, and ultraviolet protectives which have started to seek considerable attention among researchers and consumers due to the undesirable effect of chemical-based constituents on human health and environment. With the booming antiaging strategies, beauty has become the prime factor in considering one's health and overall "wellness". As promoting healthy aging is essential, the objective of aesthetic dermatology should shift from cosmetic interventions to the betterment of quality of life of aging society. The paper also discusses on certain artificial learning/machine-based algorithms, useful in screening of bioactive ingredients, helpful in developing of more tailored formulations. This narrative overview on skin antiaging natural bioactives and artificial learning-based bioactive screening approaches contributes for the improvement in dermatological drug discovery, in the development of novel targeted lead compounds and accelerates aging research and pharmaceutical research.

Characterizing Sex Differences in Mitochondrial Dysfunction After Severe Traumatic Brain Injury in Mice.

Traumatic brain injury (TBI) is caused by an impact or penetrating injury to the head resulting in abnormal brain function. Mitochondrial dysfunction is an important hallmark of TBI and has been thoroughly studied in male rodent models of brain injury, but relatively little is known about these outcomes in females. These studies were designed to examine sex as a biological variable for mitochondria-related outcomes after the severe controlled cortical impact (CCI) mouse model of TBI. Synaptic and non-synaptic mitochondria were isolated from the sham- or CCI-injured cortex as well as the hippocampus ipsilateral to the craniotomy 3, 12, 24, or 48 h post-surgery, and then bioenergetics were measured. Subtle variations were observed in the timeline of mitochondrial dysfunction between sexes. Non-synaptic cortical mitochondria from injured females showed early impairment at 12 h post-CCI compared to mitochondria from injured males at 24 h post-CCI. Contrastingly, in the synaptic fraction, mitochondria from injured males showed early impairment at 12 h post-CCI, whereas mitochondria from injured females showed impairment at 24 h post-CCI. Based on bioenergetic impairments at 24 h post-CCI, synaptic and non-synaptic mitochondrial calcium loading was also measured at this time point. Consistent with bioenergetic data at 24 h, non-synaptic mitochondria from injured males had increased calcium loading compared to uninjured control, but this effect was not observed in females. Finally, histological assessment of cortical tissue sparing in each sex was measured at 7 days post-injury. There was a lack of sex-based differences in cortical tissue sparing after severe CCI. Overall, there were some subtle sex differences in mitochondrial outcomes after CCI, but these findings were not statistically significant. This study highlights the importance of utilizing both sexes when measuring mitochondrial function after severe CCI.

Mitochondrial Dysfunction After Repeated Mild Blast Traumatic Brain Injury Is Attenuated by a Mild Mitochondrial Uncoupling Prodrug.

Mild traumatic brain injury (mTBI) results in impairment of brain metabolism, which is propagated by mitochondrial dysfunction in the brain. Mitochondrial dysfunction has been identified as a pathobiological therapeutic target to quell cellular dyshomeostasis. Further, therapeutic approaches targeting mitochondrial impairments, such as mild mitochondrial uncoupling, have been shown to alleviate behavioral alterations after TBI. To examine how mild mitochondrial uncoupling modulates acute mitochondrial outcomes in a military-relevant model of mTBI, we utilized repeated blast overpressure of 11 psi peak overpressure to model repeated mild blast traumatic brain injury (rmbTBI) in rats followed by assessment of mitochondrial respiration and mitochondrial-related oxidative damage at 2 days post-rmbTBI. Treatment groups were administered 8 or 80 mg/kg MP201, a prodrug of 2,4 dinitrophenol (DNP) that displays improved pharmacokinetics compared with its metabolized form. Synaptic and glia-enriched mitochondria were isolated using fractionated a mitochondrial magnetic separation technique. There was a consistent physiological response, decreased heart rate, following mbTBI among experimental groups. Although there was a lack of injury effect in mitochondrial respiration of glia-enriched mitochondria, there were impairments in mitochondrial respiration in synaptic mitochondria isolated from the prefrontal cortex (PFC) and the amygdala/entorhinal/piriform cortex (AEP) region. Impairments in synaptic mitochondrial respiration were rescued by oral 80 mg/kg MP201 treatment after rmbTBI, which may be facilitated by increases in complex II and complex IV activity. Mitochondrial oxidative damage in glia-enriched mitochondria was increased in the PFC and hippocampus after rmbTBI. MP201 treatment alleviated elevated glia-enriched mitochondrial oxidative damage following rmbTBI. However, there was a lack of injury-associated differences in oxidative damage in synaptic mitochondria. Overall, our report demonstrates that rmbTBI results in mitochondrial impairment diffusely throughout the brain and mild mitochondrial uncoupling can restore mitochondrial bioenergetics and oxidative balance.

LRP1 Deficiency Promotes Mitostasis in Response to Oxidative Stress: Implications for Mitochondrial Targeting after Traumatic Brain Injury.

The brain undergoes oxidative stress and mitochondrial dysfunction following physiological insults such as Traumatic brain injury (TBI), ischemia-reperfusion, and stroke. Pharmacotherapeutics targeting mitochondria (mitoceuticals) against oxidative stress include antioxidants, mild uncouplers, and enhancers of mitochondrial biogenesis, which have been shown to improve pathophysiological outcomes after TBI. However, to date, there is no effective treatment for TBI. Studies have suggested that the deletion of LDL receptor-related protein 1 (LRP1) in adult neurons or glial cells could be beneficial and promote neuronal health. In this study, we used WT and LRP1 knockout (LKO) mouse embryonic fibroblast cells to examine mitochondrial outcomes following exogenous oxidative stress. Furthermore, we developed a novel technique to measure mitochondrial morphometric dynamics using transgenic mitochondrial reporter mice mtD2g (mitochondrial-specific Dendra2 green) in a TBI model. We found that oxidative stress increased the quantity of fragmented and spherical-shaped mitochondria in the injury core of the ipsilateral cortex following TBI, whereas rod-like elongated mitochondria were seen in the corresponding contralateral cortex. Critically, LRP1 deficiency significantly decreased mitochondrial fragmentation, preserving mitochondrial function and cell growth following exogenous oxidative stress. Collectively, our results show that targeting LRP1 to improve mitochondrial function is a potential pharmacotherapeutic strategy against oxidative damage in TBI and other neurodegenerative diseases.

Calcium homeostasis in vascular smooth muscle cells is altered in type 2 diabetes by Bcl-2 protein modulation of InsP3R calcium release channels.

This study examines the extent to which the antiapoptotic Bcl-2 proteins Bcl-2 and Bcl-x(L) contribute to diabetic Ca(2+) dysregulation and vessel contractility in vascular smooth muscle cells (VSMCs) through their interaction with inositol 1,4,5-trisphosphate receptor (InsP(3)R) intracellular Ca(2+) release channels. Measurements of intracellular ([Ca(2+)](i)) and sarcoplasmic reticulum ([Ca(2+)](SR)) calcium concentrations were made in primary cells isolated from diabetic (db/db) and nondiabetic (db/m) mice. In addition, [Ca(2+)](i) and constriction were recorded simultaneously in isolated intact arteries. Protein expression levels of Bcl-x(L) but not Bcl-2 were elevated in VSMCs isolated from db/db compared with db/m age-matched controls. In single cells, InsP(3)-evoked [Ca(2+)](i) signaling was enhanced in VSMCs from db/db mice compared with db/m. This was attributed to alterations in the intrinsic properties of the InsP(3)R itself because there were no differences between db/db and db/m in the steady-state [Ca(2+)](SR) or InsP(3)R expression levels. Moreover, in permeabilized cells the rate of InsP(3)R-dependent SR Ca(2+) release was increased in db/db compared with db/m VSMCs. The enhanced InsP(3)-dependent SR Ca(2+) release was attenuated by the Bcl-2 protein inhibitor ABT-737 only in diabetic cells. Application of ABT-737 similarly attenuated enhanced agonist-induced [Ca(2+)](i) signaling only in intact aortic and mesenteric db/db vessels. In contrast, ABT-737 had no effect on agonist-evoked contractility in either db/db or db/m vessels. Taken together, the data suggest that in type 2 diabetes the mechanism for [Ca(2+)](i) dysregulation in VSMCs involves Bcl-2 protein-dependent increases in InsP(3)R excitability and that dysregulated [Ca(2+)](i) signaling does not appear to contribute to increased vessel reactivity.

Development and validation of a highly sensitive LC-MS/MS-ESI method for the determination of bicalutamide in mouse plasma: application to a pharmacokinetic study.

A highly sensitive, rapid assay method has been developed and validated for the estimation of bicalutamide in mouse plasma using liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the negative-ion mode. The assay procedure involves extraction of bicalutamide and tolbutamide (internal standard, IS) from mouse plasma with a simple protein precipitation method. Chromatographic separation was achieved using an isocratic mobile phase (0.2% formic acid:acetonitrile, 35:65, v/v) at a flow rate of 0.5 mL/min on an Atlantis dC18 column (maintained at 40 ± 1°C) with a total run time of 3.0 min. The MS/MS ion transitions monitored were m/z 428.9 → 254.7 for bicalutamide and m/z 269.0 → 169.6 for IS. Method validation was performed as per FDA guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 1.04 ng/mL and the linearity range extended from 1.04 to 1877 ng/mL. The intra- and inter-day precisions were in the ranges of 0.49-4.68 and 2.62-4.15, respectively.

Development and validation of an LC-MS/MS-ESI method for the determination of lorglumide, a CCK-1 antagonist in mouse plasma: application to a pharmacokinetic study.

A highly sensitive, rapid assay method was developed and validated for the estimation of lorglumide in mouse plasma using liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in positive-ion mode. The assay procedure involves extraction of lorglumide and phenacetin (internal standard, IS) from mouse plasma with simple protein precipitation. Chromatographic separation was achieved using an isocratic mobile (0.2% formic acid solution-acetonitrile, 20:80, v/v) at a flow-rate of 0.5 mL/min on an Atlantis dC18 column maintained at 40 °C with a total run time of 4.0 min. The MS/MS ion transitions monitored were 459.2 → 158.4 for lorglumide and 180.1 → 110.1 for IS. Method validation was performed as per FDA guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 0.42 ng/mL and the linearity range extended from 0.42 to 500 ng/mL. The intra- and inter-day precisions were in the ranges of 1.47-10.9 and 3.56-7.53, respectively.

Resilience of females to acute blood-brain barrier damage and anxiety behavior following mild blast traumatic brain injury.

Low-level blast exposure can result in neurological impairment for military personnel. Currently, there is a lack of experimental data using sex as a biological variable in neurovascular outcomes following blast exposure. To model mild blast traumatic brain injury (mbTBI), male and female rats were exposed to a single 11 psi static peak overpressure blast wave using the McMillan blast device and cohorts were then euthanized at 6 h, 24 h, 7 d and 14 d post-blast followed by isolation of the amygdala. After mbTBI, animals experience immediate bradycardia, although no changes in oxygen saturation levels or weight loss are observed. Male mbTBI animals displayed significantly higher levels of anxiety-like behavior (open field and elevated plus maze) compared to male sham groups; however, there was no anxiety phenotype in female mbTBI animals. Blast-induced neurovascular damage was explored by measuring expression of tight junction (TJ) proteins (zonula occludens-1 (ZO-1), occludin and claudin-5), glial fibrillary acidic protein (GFAP) and astrocyte end-feet coverage around the blood-brain barrier (BBB). Western blot analysis demonstrates that TJ protein levels were significantly decreased at 6 h and 24 h post-mbTBI in male rats, but not in female rats, compared to sham. Female animals have decreased GFAP at 6 h post-mbTBI while male animals display decreased GFAP expression at 24 h post-mbTBI. By 7 d post-mbTBI, there were no significant differences in TJ or GFAP levels between groups in either sex. At 24 h post-mbTBI, vascular integrity and astrocytic end-feet coverage around the BBB was significantly decreased in males following mbTBI. These results demonstrate that loss of GFAP expression may be due to astrocytic damage at the BBB. Our findings also demonstrate sex differences in acute vascular and behavioral outcomes after single mbTBI. Female animals display a lack of BBB pathology after mbTBI corresponding to improved acute neuropsychological outcomes as compared to male animals.

Apoptosis protection by Mcl-1 and Bcl-2 modulation of inositol 1,4,5-trisphosphate receptor-dependent Ca2+ signaling.

Members of the Bcl-2 protein family play a central role in the regulation of apoptosis. An interaction between anti-apoptotic Bcl-x(L) and the endoplasmic reticulum (ER)-localized inositol trisphosphate receptor Ca(2+) release channel (InsP(3)R) enables Bcl-x(L) to be fully efficacious as an anti-apoptotic mediator (White, C., Li, C., Yang, J., Petrenko, N. B., Madesh, M., Thompson, C. B., and Foskett, J. K. (2005) Nat. Cell Biol. 7, 1021-1028). Physiologically, Bcl-x(L) binds to the InsP(3)R to enhance its gating and Ca(2+) signaling. Here we have discovered that structurally related proteins Bcl-2 and Mcl-1 function similarly. Bcl-2, Mcl-1 and Bcl-x(L) bind with comparable affinity to the carboxyl termini of all three mammalian InsP(3)R isoforms with important functional consequences. Stable expression of Bcl-2 or Mcl-1 lowered ER Ca(2+) content and enhanced the rate of InsP(3)-mediated Ca(2+) release in response to submaximal InsP(3) stimulation in permeabilized wild-type DT40 cells but not in cells lacking InsP(3)R. In addition, expression of either Bcl-2 or Mcl-1 enhanced spontaneous InsP(3)R-dependent Ca(2+) oscillations and spiking in intact cells in the absence of agonist stimulation. Bcl-2- and Mcl-1-mediated protection from apoptosis induced by staurosporine or etoposide was enhanced in cells expressing InsP(3)R, demonstrating that their interactions with InsP(3)R enable Bcl-2 and Mcl-1 to be fully efficacious anti-apoptotic mediators. Our data suggest a molecular mechanism that is shared by several anti-apoptotic Bcl-2 proteins that provides apoptosis resistance by direct interactions at the ER with the InsP(3)R that impinges on cellular Ca(2+) homeostasis.

Sustained release optimized formulation of anastrozole-loaded chitosan microspheres: in vitro and in vivo evaluation.

The purpose of this study was to develop sustained release formulation of anastrozole-loaded chitosan microspheres for treatment of breast cancer. Chitosan microspheres cross-linked with two different cross-linking agents viz, tripolyphosphate (TPP) and glutaraldehyde (GA) were prepared using single emulsion (w/o) method. A reverse phase HPLC method was developed and used for quantification of drug in microspheres and rat plasma. Influence of cross-linking agents on the properties of chitosan microspheres was extensively investigated. Formulations were characterized for encapsulation efficiency (EE), compatibility of drug with excipients, particle size, surface morphology, swelling capacity, erosion and drug release profile in phosphate buffer pH 7.4. EE varied from 30.4 ± 1.2 to 69.2 ± 3.2% and mean particle size distribution ranged from 72.5 ± 0.5 to 157.9 ± 1.5 µm. SEM analysis revealed smooth and spherical nature of microspheres. TPP microspheres exhibited higher swelling capacity, percentage erosion and drug release compared to GA microspheres. Release of anastrozole (ANS) was rapid up to 4 h followed by slow release status. FTIR analysis revealed no chemical interaction between drug and polymer. DSC analysis indicated ANS trapped in the microspheres existed in amorphous form in polymer matrix. The highest correlation coefficients (R (2)) were obtained for Higuchi model, suggesting a diffusion controlled mechanism. There was significant difference in the pharmacokinetic parameters (AUC(0-∞), Kel and t(1/2)) when ANS was formulated in the form of microspheres compared to pure drug. This may be attributed to slow release rate of ANS from chitosan microspheres and was detectable in rat plasma up to 48 h which correlates well with the in vitro release data.

Bioaccumulation of heavy metals in water, sediment, and tissues of major fisheries from Adyar estuary, southeast coast of India: An ecotoxicological impact of a metropolitan city.

Heavy metal content in water, sediment, and tissues of six commonly used edible fishes from Adyar estuary, southeast coast of India, was assessed for metal bioaccumulation. The enrichment of metals in estuarine sediment is due to the discharge of contaminated water from the Chennai Metropolis. The enrichment factor indicated that metals such as Cr (EF=30.9) and Cu (EF=31.9) are highly enriched and fall under the very severe category. Bioaccumulation factor (BAF) revealed that the concentration of heavy metals viz. Ni, Cr, Pb, Cu, Co, Zn, Fe, and Mn in different tissues of fishes was several times higher than their concentrations in water. Moreover, high concentration of heavy metals, especially Cu and Cr was noticed in the muscle and liver tissues of the fishes which are higher than the WHO standards. Among the studied fishes, Arius parkii and Gerres oyena showed higher levels of bioaccumulation in terms of toxic metals.