Apolipoprotein E-Dependent Differences in Innate Immune Responses of Maturing Human Neuroepithelial Progenitor Cells Exposed to HIV-1

HIV enters the brain early during infection and induces a chronic inflammatory state that can result in neurological abnormalities in a subset of infected individuals. To investigate the effects of HIV exposure on neurogenesis and neuronal survival in the brain, we have used a model system consisting of human neuroepithelial progenitor (NEP) cells that undergo directed differentiation into astrocytes and neurons in vitro. Changes in gene expression in NEP cultures as a result of HIV exposure were investigated using gene expression microarrays with the Illumina HT-12 V4_0_R1 platform array. Through this approach, we identified a group of genes specifically upregulated by exposure to virus that are strongly related to interferon induced responses and antigen presentation. When the data were stratified by their apolipoprotein genotype, this innate immune response was more robust in the apolipoprotein E3/E3 genotype cultures than in the apolipoprotein E3/E4 counterparts. Biological processes as defined by the gene ontology (GO) program were also differently affected upon virus exposure in cultures of the two genotypes, particularly those related to antigen presentation and the actions of interferons. Differences occurred in both in numbers of genes affected and their significance in the GO processes in which they participate, with apoE3/E3?> apoE3/E4. These data suggest that maturing NEP cultures recognize HIV and respond to it by mounting an innate immune response with a vigor that is influenced by the apolipoprotein E genotype of the cells.     

Impact of pretransplant splenectomy on patients with beta-thalassemia major undergoing a matched-related allogeneic stem cell transplantation

Impact of pretransplant splenectomy in patients with beta-thalassemia major undergoing an allogeneic SCT has never been addressed. Twenty-seven class III patients (29 transplants) had a pretransplant splenectomy. The outcome of these 29 transplants was compared with 76 transplants in class III who did not have a splenectomy. Patients in the splenectomy group were older (11.7 +/- 5.0 vs. 8.5 +/- 3.5 yr; p = 0.003) and had a larger liver size (5.7 +/- 1.8 vs. 4.4 +/- 1.6 cm; p = 0.000). Splenectomized patients had a significantly faster time to ANC >500/mm(3) (15.4 +/- 5.9 vs. 17.5 +/- 4 days; p = 0.002) and platelet >20 000/mm(3) (22.5 +/- 6.7 vs. 32.5 +/- 13.6 days; p = 0.000). The splenectomized group had a significantly reduced requirement of blood transfusion in the first 100 days post-transplant (5.5 +/- 5.1 vs. 7.2 +/- 5.4 units; p = 0.017). There were significantly more deaths related to peri-transplant infections in the post-splenectomy group (24% vs. 5.3%; p = 0.0001). The graft rejections were comparable between the two groups (20.7% vs. 14.5%; p = 0.55). The incidence of acute and chronic GVHD, late infections, and deaths from RRT was not significantly different between the two groups. The five-yr EFS (31.0 +/- 8.6 vs. 60.8 +/- 5.98; p = 0.003) and OS (39.7 +/- 9.3 vs. 71.8 +/- 5.5; p = 0.002) was significantly worse in the splenectomized group. In conclusion, pretransplant splenectomy among patients with beta-thalassemia major was associated with faster engraftment, reduced transfusion support, a higher incidence of peri-transplant infection related deaths, and a reduced EFS and OS.     

An investigation on the antibacterial, cytotoxic, and antibiofilm efficacy of starch-stabilized silver nanoparticles

The increased emergence of drug resistant microbes creates a major challenge to the scientific community for successful development of effective therapeutics. The antimicrobial activities of silver ions are well known, but limited information is available on the effects of green silver-nanoparticles (AgNPs) on human pathogens. In this article, we evaluated the antibacterial activity of starch-stabilized AgNPs against a panel of human pathogens commonly associated with air, water and food borne infections. The shape and size distribution of AgNPs were characterized by transmission electron microscopy. We showed that AgNPs were more effective against Gram-positive and Gram-negative pathogens as compared with acid-fast bacteria. AgNPs were not cytotoxic to macrophages at the bactericidal concentration and can augment intracellular killing potential of macrophages. Furthermore, we showed that AgNPs disrupt biofilm formation and exhibit better antibacterial activity compared to human cationic antimicrobial peptide LL-37. In summary, our data suggest AgNPs as a promising template for the design of novel antibacterial agents.     

Dynamics of coregulator-induced conformational perturbations in androgen receptor ligand binding domain

Extracts from the plant Pygeum africanum are widely used in the therapy of benign prostate hyperplasia (BPH) and in combinational therapy for prostate cancer, the second leading cause of cancer death and the mostly diagnosed form of cancer in men. The androgen receptor (AR) plays a crucial role in the development of the prostate as well as in prostate diseases. Even though the extracts from P. africanum are considered as beneficial for prostate diseases in clinical trials, and some active compounds for treatment of BPH could be identified, compounds responsible for AR inhibition and the molecular mechanism for inhibition of prostatitis need to be identified. Recently, atraric acid and N-butylbenzene-sulfonamide were isolated from a selective dichlormethane extract of P. africanum as two novel AR antagonistic compounds. The molecular mechanisms of AR inhibition were analyzed and are summarized here. Both compounds are the first known natural, complete and specific AR antagonist.     

Lyme Borreliosis and Skin

Lyme disease is a multisystem illness which is caused by the strains of spirochete Borrelia burgdorferi sensu lato and transmitted by the tick, Ixodes. Though very commonly reported from the temperate regions of the world, the incidence has increased worldwide due to increasing travel and changing habitats of the vector. Few cases have been reported from the Indian subcontinent too. Skin manifestations are the earliest to occur, and diagnosing these lesions followed by appropriate treatment, can prevent complications of the disease, which are mainly neurological. The three main dermatological manifestations are erythema chronicum migrans, borrelial lymphocytoma and acrodermatitis chronica atrophicans. Many other dermatological conditions including morphea, lichen sclerosus and lately B cell lymphoma, have been attributed to the disease. Immunofluorescence and polymerase reaction tests have been developed to overcome the problems for diagnosis. Culture methods are also used for diagnosis. Treatment with Doxycycline is the mainstay of management, though prevention is of utmost importance. Vaccines against the condition are still not very successful. Hence, the importance of recognising the cutaneous manifestations early, to prevent systemic complications which can occur if left untreated, can be understood. This review highlights the cutaneous manifestations of Lyme borreliosis and its management.     

Neuropsychological performance in OCD: a study in medication-naïve patients

Background

Obsessive-compulsive disorder (OCD) is associated with impairments in multiple neuropsychological domains but the findings are rather inconsistent across studies. One potential reason for poor replication is the confounding influence of medications. There is limited research on neuropsychological performance in medication-naïve, never treated OCD patients.

Methods

In this study, we assessed 31 medication-naïve, never-treated, DSM-IV OCD patients free of comorbid major depression and 31 healthy controls individually matched for age, gender and years of education, with tests of attention, executive function, memory reasoning and visuo-spatial function.

Results

Medication-naïve OCD patients did not significantly differ from healthy controls on most neuropsychological tests. Patients performed somewhat poorly only on the highest goal hierarchy of the Tower of London (TOL) test (p = 0.001, effect size = 0.68).

Conclusions

It is intriguing to find that symptomatic, drug-naïve OCD patients did not significantly differ from healthy controls on most neuropsychological tests. Our finding of medium effect size on TOL highest goal hierarchy test suggests that brain regions outside the affective orbitofrontal loop may also be perhaps involved in OCD. This finding however needs replication because of modest effect size. Future studies should focus on studying medication-naïve, co-morbidity-free patients and relatives using symptom dimensions for consistent and robust findings.     

Behavioral evaluation of visual function of rats using a visual discrimination apparatus

A visual discrimination apparatus was developed to evaluate the visual sensitivity of normal pigmented rats (n=13) and S334ter-line-3 retinal degenerate (RD) rats (n=15). The apparatus is a modified Y maze consisting of two chambers leading to the rats' home cage. Rats were trained to find a one-way exit door leading into their home cage, based on distinguishing between two different visual alternatives (either a dark background or black and white stripes at varying luminance levels) which were randomly displayed on the back of each chamber. Within 2 weeks of training, all rats were able to distinguish between these two visual patterns. The discrimination threshold of normal pigmented rats was a luminance level of -5.37+/-0.05 log cd/m(2); whereas the threshold level of 100-day-old RD rats was -1.14+/-0.09 log cd/m(2) with considerable variability in performance. When tested at a later age (about 150 days), the threshold level of RD rats was significantly increased (-0.82+/-0.09 log cd/m(2), p<0.03, paired t-test). This apparatus could be useful to train rats at a very early age to distinguish between two different visual stimuli and may be effective for visual functional evaluations following therapeutic interventions.