The histone deacetylase inhibitor, sodium butyrate, alleviates cognitive deficits in pre-motor stage PD

Parkinson's disease (PD) patients often times experience impairment in their cognitive abilities early on in the progression of the disease. The reported deficits appear to mainly involve functions that are associated with frontal lobe and frontal-striatal pathways subserving attentional set-shifting, working memory and executive function. The current study explored executive function deficits in a rat model of PD in the pre-motor deficit stage. The rats were lesioned with 12 μg of 6-hydroxydonpamine (6-OHDA) in the striatum in a two step process (10 μg/μl followed by 2 μg/μl) 48 hours apart. Executive function was tested at 3 weeks post-surgery using a rat analogue of Wisconsin card sorting test called the Extra Dimensional/Intra Dimensional (ED/ID) set-shifting task. The results demonstrated that performance by the pre-motor rat model of PD was equivalent to that of the control groups in the simple and the compound discriminations as well as the intra-dimensional set-shifting. However the PD group exhibited attentional set-shifting deficits similar to those observed in PD patients. Additionally, sodium butyrate, a short chain fatty acid derivative and inhibitor of class I and II histone deacetylase (HDACi), was tested as a potential therapeutic agent to mitigate the pre-motor cognitive deficits in PD. The results indicated that the sodium butyrate treatment not only effectively alleviated the set-shifting deficits, but also improved the attentional set formation in the treated rats.     

Gold-peptide nanoconjugate cellular uptake is modulated by serum proteins

Gold nanoparticles (Au NPs, 20 nm) were conjugated with two different cysteine-terminated peptides. Radio-ligand binding studies were conducted to characterize Au NP-peptide binding, suggesting both covalent and noncovalent interactions. The interactions of serum proteins with Au NP-peptide nanoconjugates were determined using gel electrophoresis and dynamic light scattering. Serum proteins rapidly bound the nanoconjugates (15 minutes). The cellular uptake of free peptides and nanoconjugates into mouse myogenic (Sol8) cells was investigated in the absence or presence of serum. In the absence of serum, peptides presented as nanoconjugates showed significantly higher intracellular fluorescence signals compared to those in the presence of serum (P < 0.05), suggesting that serum proteins inhibit Au NP-mediated peptide delivery. The cellular uptake of nanoconjugates was also confirmed using transmission electron microscopy. These data suggest that Au NP-peptide nanoconjugates are a useful platform for intracellular delivery of therapeutics. However, a deeper understanding of the mechanisms regulating their uptake and intracellular trafficking is needed.     

Severity assessment tools to guide ICU admission in community-acquired pneumonia: systematic review and meta-analysis

Background  

The aim of this meta-analysis was to determine if severity assessment tools can be used to guide decisions regarding intensive care unit (ICU) admission of patients with community-acquired pneumonia.     

Linkage Disequilibrium Pattern in Asthma Candidate Genes from 5q31‐q33 in the Singapore Chinese Population

Studies have shown linkage between microsatellite markers from the chromosome 5q31‐q33 region with asthma, atopy and total IgE levels in the Singapore Chinese population. However, subsequent case‐control studies failed to show association between the polymorphisms in the candidate genes from this region and asthma or related phenotypes. In this study, we investigated 20 asthma candidate genes from this region for all possible informative polymorphisms within our population, linkage disequilibrium (LD) structure and tagging SNP transferability from HapMap populations. We re‐sequenced these genes and identified 267 polymorphisms including 26 insertion‐deletions, four microsatellite markers and 237 single nucleotide polymorphisms. The region contained 17 distinct LD blocks with the largest within the serine peptidase inhibitor kazal type 5 (SPINK5) gene spanning 23 kb. Of the 267 polymorphisms identified, 40% are represented in HapMap Han Chinese from Beijing and 29% in Han Chinese from Denver. 72% of the polymorphisms can be represented by tagged SNPs from the HapMap Beijing Han Chinese population and are highly correlated in terms of minor allele frequencies and LD structure. Our data suggest that although the HapMap Han Chinese population from Beijing is very similar to the Singapore Chinese population, this similarity is insufficient to account for up to 28% of the polymorphisms in the local population.     

A cluster randomized,controlled trial of breast and cervix cancer screening in Mumbai,India: methodology and interim results after three rounds of screening

Cervix and Breast cancers are the most common cancers among women worldwide and extract a large toll in developing countries. In May 1998, supported by a grant from the NCI (US), the Tata Memorial Hospital, Mumbai, India, started a cluster‐randomized, controlled, screening‐trial for cervix and breast cancer using trained primary health workers to provide health‐education, visual‐inspection of cervix (with 4% acetic acid‐VIA) and clinical breast examination (CBE) in the screening arm, and only health education in the control arm. Four rounds of screening at 2‐year intervals will be followed by 8 years of monitoring for incidence and mortality from cervix and breast cancers. The methodology and interim results after three rounds of screening are presented here. Good randomization was achieved between the screening (n = 75360) and control arms (n = 76178). In the screening arm we see: High screening participation rates; Low attrition; Good compliance to diagnostic confirmation; Significant downstaging; Excellent treatment completion rate; Improving case fatality ratios. The ever‐screened and never‐screened participants in the screening arm show significant differences with reference to the variables religion, language, age, education, occupation, income and health‐seeking behavior for gynecological and breast‐related complaints. During the same period, in the control arm we see excellent participation rate for health education; Low attrition and a good number of symptomatic referrals for both cervix and breast.     

Quercetin mediated reduction of angiogenic markers and chaperones in DLA-induced solid tumours

Diet-derived flavonoids, in particular quercetin, may play advantageous roles by preventing or/and inhibiting oncogenesis. Evidence suggests that quercetin can elicit various properties depending on the cell type. The aim of this study was to evaluate its effects on Dalton's lymphoma ascites (DLA) induced solid tumours and to identify the target(s) of action. We addressed this question by inducing subcutaneous solid tumours in Swiss albino mice and investigated whether the quercetin affects essential biological processes that are responsible for tumour growth, morphology, angiogenesis and apoptosis. We also studied influence on several heat shock proteins (HSPs). Our findings demonstrate that intra-tumour administration of quercetin results in decreased volume/weight. Furthermore, we demonstrate that quercetin promotes apoptosis of cancer cells by down-regulating the levels of Hsp90 and Hsp70. Depletion of these two chaperones by quercetin might result in triggering of caspase-3 in treated tumours. Moreover, it also down-regulated the expression of major key angiogenic or pro-angiogenic factors, like HIF-1α and VEGF In addition, H and E staining together with immunofluorescence of fixed tumour tissue provided evidence in support of increased cell death in quercetin-treated mice.     

Disseminated superficial and warty type of porokeratosis: a rare coexistence

A 60-year-old male presented with hyperpigmented annular plaques with raised keratotic wall and central groove along with warty plaque involving the trunk and the extremities, respectively. A provisional diagnosis of porokeratosis was made which was confirmed histopathologically. Herein, we report a case of rare coexistence of disseminated superficial and warty porokeratosis.     

Supercritical Fluid Technology-Based Trans-Resveratrol SLN for Long Circulation and Improved Radioprotection

Purpose

To alleviate the harmful effects of radiations during occupational radiology, radiotherapy and diagnosis, radioprotective system with lower toxicity and extended activity is imperative. Trans-resveratrol (RVL) acts through free radical scavenging/antioxidant mechanism to mitigate the radiation-induced damage. But, its poor solubility and fast metabolism impede its efficacy. Thus, encapsulation of RVL into long circulating solid lipid nanoparticle (SLN) is aimed.

Method

Supercritical CO₂ solution of RVL, Gelucire®50/02 and Gelucire®50/13 SLN, was rapidly expanded into aqueous phase containing Tween 80, sonicated and lyophilized to get SLN. Particle size, polydispersity index (PDI), entrapment efficiency (%EE), scanning electron microscopy (SEM), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), drug release, in vivo pharmacokinetics, antioxidant assays, radiation-induced lipid peroxidation and plasmid DNA relaxation assays were studied. Stability studies were performed to analyze drug degradation and shelf life.

Results

Optimized formulation (F9) had %yield, particle size, PDI, %EE and %drug release (after 72 h) of 68.48?±?5.73 %, 276.7?±?5.33 nm, 0.18?±?0.032, 62.66?±?4.52 % and 70.05?±?3.003 %, respectively. Electron microscopy revealed nearly spherical particles, while DSC and XRD showed reduced crystalline peaks. F9 showed higher AUC and sustained release of RVL in rats (i.v. bolus) and increased antioxidant activities and radioprotection as compared to RVL solution. Shelf life of >2 years was predicted for F9 (at 8 °C).

Conclusion

Results are encouraging to use F9 for radiation exposure prophylaxis.