Polyphosphate and associated enzymes as global regulators of stress response and virulence in Campylobacter jejuni

Campylobacter jejuni (C. jejuni), a Gram-negative microaerophilic bacterium, is a predominant cause of bacterial foodborne gastroenteritis in humans worldwide. Despite its importance as a major foodborne pathogen, our understanding of the molecular mechanisms underlying C. jejuni stress survival and pathogenesis is limited. Inorganic polyphosphate (poly P) has been shown to play significant roles in bacterial resistance to stress and virulence in many pathogenic bacteria. C. jejuni contains the complete repertoire of enzymes required for poly P metabolism. Recent work in our laboratory and others have demonstrated that poly P controls a plethora of C. jejuni properties that impact its ability to survive in the environment as well as to colonize/infect mammalian hosts. This review article summarizes the current literature on the role of poly P in C. jejuni stress survival and virulence and discusses on how poly P-related enzymes can be exploited for therapeutic/prevention purposes. Additionally, the review article identifies potential areas for future investigation that would enhance our understanding of the role of poly P in C. jejuni and other bacteria, which ultimately would facilitate design of effective therapeutic/preventive strategies to reduce not only the burden of C. jejuni-caused foodborne infections but also of other bacterial infections in humans.     

Antidepressant activity of Asparagus racemosus in rodent models

Asparagus racemosus Linn. (AR) is an Ayurvedic rasayana used as an adaptogen. Adaptogenic drugs are those which are useful as anti-stress agents by promoting non-specific resistance of the body. Although, the adaptogenic effect of AR is well documented, its use in psychological disorders like depression is not scientifically evaluated. Hence, the present investigation evaluates the antidepressant effect of methanolic extract of roots of AR (MAR) standardized to saponins (62.2% w/w). Rats were given MAR in the doses of 100, 200 and 400 mg/kg daily for 7 days and then subjected to forced swim test (FST) and learned helplessness test (LH). The results show that MAR decreases immobility in FST and increases avoidance response in LH indicating antidepressant activity. In behavioral experiments, MAR increased the number of head twitches produced by 5-HTP and increased clonidine-induced aggressive behavior indicating facilitatory effect on both serotonergic and adrenergic systems respectively. However, MAR had insignificant effect on l-DOPA-induced aggressive behavior indicating absence of activity on dopaminergic system. MAR also reversed changes to the endogenous antioxidant system induced by FST. Thus, MAR has significant antidepressant activity and this effect is probably mediated through the serotonergic and the noradrenergic systems and augmentation of antioxidant defenses.     

Attenuated bioluminescent Brucella melitensis mutants GR019 (virB4), GR024 (galE), and GR026 (BMEI1090-BMEI1091) confer protection in mice

In vivo bioluminescence imaging is a persuasive approach to investigate a number of issues in microbial pathogenesis. Previously, we have applied bioluminescence imaging to gain greater insight into Brucella melitensis pathogenesis. Endowing Brucella with bioluminescence allowed direct visualization of bacterial dissemination, pattern of tissue localization, and the contribution of Brucella genes to virulence. In this report, we describe the pathogenicity of three attenuated bioluminescent B. melitensis mutants, GR019 (virB4), GR024 (galE), and GR026 (BMEI1090-BMEI1091), and the dynamics of bioluminescent virulent bacterial infection following vaccination with these mutants. The virB4, galE, and BMEI1090-BMEI1091 mutants were attenuated in interferon regulatory factor 1-deficient (IRF-1(-/-)) mice; however, only the GR019 (virB4) mutant was attenuated in cultured macrophages. Therefore, in vivo imaging provides a comprehensive approach to identify virulence genes that are relevant to in vivo pathogenesis. Our results provide greater insights into the role of galE in virulence and also suggest that BMEI1090 and downstream genes constitute a novel set of genes involved in Brucella virulence. Survival of the vaccine strain in the host for a critical period is important for effective Brucella vaccines. The galE mutant induced no changes in liver and spleen but localized chronically in the tail and protected IRF-1(-/-) and wild-type mice from virulent challenge, implying that this mutant may serve as a potential vaccine candidate in future studies and that the direct visualization of Brucella may provide insight into selection of improved vaccine candidates.     

A phase 1 trial of intravenous 4-(N-(S-glutathionylacetyl)amino) phenylarsenoxide (GSAO) in patients with advanced solid tumours

Background

4-(N-(S-glutathionylacetyl)amino) phenylarsenoxide (GSAO) is a water-soluble mitochondrial toxin that binds to adenine nucleotide translocase in the inner mitochondrial membrane, thereby targeting cell proliferation. This phase 1 study investigated safety, dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and pharmacokinetics (PK) of GSAO as a daily 1-h infusion for 5 days a week for 2 weeks in every three. Pharmacodynamics of GSAO was evaluated by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and circulating markers of angiogenesis.

Methods

Patients with advanced solid tumours received GSAO in a dose-escalation trial according to a standard ‘3 + 3’ design that was guided by toxicity and, for the final dose escalation, by arsenic PK data.

Results

A total of 34 patients were treated with GSAO across 9 dose levels (1.3–44.0 mg/m²). Treatment was well tolerated with few adverse events. An additional three patients were enrolled at the 12.4 mg/m² dose level following a DLT of derangement of liver function tests (grade 4). At the 44.0 mg/m² dose level, two out of three patients had DLTs (reversible encephalopathy; paroxysmal atrial fibrillation).

Conclusions

The MTD of GSAO was 22.0 mg/m²/day. There was no biomarker evidence from DCE-MRI or circulating markers of angiogenesis of an anti-vascular effect of GSAO.     

Effects of Blending Tobacco Lignin with HDPE on Thermal and Mechanical Properties

Depletion of fossil fuels and the detrimental environmental impacts of synthetic plastics have prompted a global interest in bio-based polymers. Lignin is an abundant, unused, and low-value byproduct of pulping and biochemical operations that has the potential to decrease the need for plastics derived from petroleum. Melt blending is one of the easiest strategies for expanding the commercial applications of lignin. Concerns remain, however, regarding the negative effects of lignin on the final composite material’s performance, and the increase in manufacturing costs. This study investigates the effects of blending lignin extracted from tobacco using a novel one-step processing technique on injection molding parameters, and the mechanical, physical, and thermal properties of high-density polyethylene (HDPE). By extruding HDPE pellets and lignin powder, varying blend concentrations (0, 5, 10, 15, and 30% wt.) were produced. Scanning electron microscopy (SEM) and optical microscopy were used to investigate the compatibility of the blend morphology. Results indicated that interfacial interactions were achieved as particles of tobacco lignin were well dispersed and uniformly distributed throughout HDPE. Intermolecular interactions between HDPE and lignin were also discovered through Fourier-transform infrared (FTIR) spectral analyses. The tensile test results showed that increase in lignin content up to 15% wt. had little effect on tensile strength, but at 30% wt., a 19% reduction was observed. With the addition of 5, 10, 15, and 30% wt. of lignin, the tensile modulus increased by 4%, 29%, 25%, and 8%, respectively. TGA results demonstrated that at 15% and 30% wt., tobacco lignin acted as a thermal stabilizer. The processability study revealed that tobacco lignin could be processed easily using injection molding without requiring significant changes to the process parameters. Overall, tobacco lignin showed great promise as a biodegradable HDPE filler.     

Assessment of Pharmacy Student Professionalism Across a Curriculum

Objectives

To evaluate changes in professionalism across the curriculum among pharmacy students in different classes.

Methods

A professionalism instrument was administered early in the first (P1) year, upon completing the introductory pharmacy practice experiences (IPPE) near the end of the second (P2) year, and upon completing the advanced pharmacy practice experiences (APPE) at the end of the fourth (P4) year.

Results

The professionalism scale and its subscales were compared for the 3 time points for the class of 2009. Significant differences were noted in professionalism scores between the P1 and P4 years and for altruism, accountability, and honor/integrity subscale scores for the class of 2009. No significant differences were noted when the scores for 4 P1 classes, and 3 P2 classes were compared.

Conclusion

An increase in professionalism scores and altruism, accountability, and honor/integrity scores was demonstrated, providing evidence that the curricular and co-curricular activities in the school of pharmacy helped develop professionalism in the class of 2009 students.     

Spontaneous chylopericardium in an adult due to mediastinal cystic hygroma

Chylopericardium is a rare and benign condition. Apart from common causes like non-surgical trauma, tuberculosis, malignancy, radiation, and postoperative, mediastinal cystic hygroma presenting as chylopericardium is an extremely rare entity. Primary or idiopathic chylopericardium is diagnosed when the precise cause is not known. It is a diagnosis of exclusion. We report a 27-year-old lady with mediastinal cystic hygroma, presenting as spontaneous chylopericardium, who was managed surgically with no recurrence on 18 months follow-up. She was evaluated for complaints of discomfort in the upper abdomen region and breathing difficulty in left lateral position for 4 days, and was found to have a large pericardial effusion with impending tamponade. She underwent pericardiocentesis, and on fluid analysis, it was confirmed as chylous pericardial effusion. She was evaluated thoroughly and was taken up for right video-assisted thoracoscopy. The thoracic duct was clipped and a window was created in the pericardium, the cystic hygroma was excised, and pleurodesis was done. The postoperative period was uneventful. Histopathology of the pericardial window showed chronic inflammatory pathology and cystic lesion was confirmed as a chylous cyst.     

Wound healing activity of the ethanol root extract and polyphenolic rich fraction from Potentilla fulgens

Context: Potentilla fulgens Wall. ex Hook (Rosaceae) is a potent medicinal plant of the Western Himalayas, where its roots are traditionally used by the local people of Uttaranchal (India) to treat wounds and tiger bites.

Objective: The present study scientifically evaluates the wound healing activity of P. fulgens ethanol root extract (EPF) and its ethyl acetate fraction (PFEA) on experimental rats.

Materials and methods: Wounds were inflicted on animals by using both excision and incision models. The wounded animals were treated for 16 days with EPF (oral: 200–400?mg/kg and topical: 5–10% w/w) and PFEA (oral: 75?mg/kg; topical: 1.75% w/w). Various physical (wound contraction, epithelialization rate, tensile strength) and biochemical parameters (hydroxyproline, hexosamine, proteins, DNA) were examined during the study. Oxidant product (lipidperoxidase), antioxidant enzymes (catalase, superoxide-dismutase) and reduced glutathione were determined. Morphological and histopathological studies of the skin tissues were monitored.

Results: A significant (p?<?0.05) wound healing property was observed when the animals were treated topically with EPF (10% w/w) and PFEA (1.75% w/w). A significantly (p?<?0.05) increased in the levels of hydroxyproline, hexosamine, protein and DNA up to 59.22, 70.42, 61.01 and 60.00% was observed, respectively. This effect was further demonstrated by the morphological and histopathological representation, thus showing significant (p?<?0.05) re-epethelialization on the healing area. EPF and PFEA also showed significant (p?<?0.05) antioxidant activity.

Conclusions: The present study provided the scientific evidence, where P. fulgens rich in polyphenolic components possess remarkable wound healing activities, thereby supporting the traditional claims.