Bentham Science Publishers (China)

In the current study we investigated the prevalence of the TNF-α 238G/A single nucleotide polymorphism (SNP) of the TNF-α gene in the development of lipodystrophy among HIV-1 infected individuals who had been receiving antiretroviral therapy (ART) in the immunodeficiency clinics of the National AIDS Research Institute (NARI) at Pune, India. We assessed the association of this SNP with the development of lipoatrophy/dyslipidemia and insulin resistance in these patients and measured carotid intima thickening which is a surrogate marker for chronic cardiac morbidity. Our results show that the incidence of the TNF-α 238G/A SNP is ~ two fold higher in patients with lipodystrophy as compared to those without lipodystrophy. Patients with lipodystrophy demonstrated a higher likelihood of the development of metabolic syndrome as evident by increased insulin sensitivity and increased percentage (%) β cell function. Further, a significant increase in left carotid intima thickness was observed in patients with lipodystrophy. Our study validates the association of the TNF-α 238G/A SNP allelic variant with the development of HIV- lipodystrophy via the modulation of TNF-α production, which contributes to dyslipidemia, increased lipolysis, increased insulin resistance, altered differentiation of adipocytes and increased carotid intima thickness. The contribution of genetic determinants such as the TNF-α 238G/A SNP to lipodystrophy, may provide insight into the mechanisms that underlie this disease condition and may be useful in the future for personalized therapy. Additionally, these findings will be useful in monitoring chronic cardiac morbidities among HIV infected individuals who express this SNP.

The most common mechanism of the so-called multidrug resistance (MDR), is mainly associated with an over expression of P-glycoprotein (Pgp). It is an ATP-dependent transport protein that limits the intracellular accumulation of a variety of structurally unrelated compounds within various organs and normal tissues such as kidney, small intestine and the blood brain barrier. Thus, the expression of Pgp has a major impact on the pharmacokinetic profile of many therapeutic agents and therefore, overcoming Pgp-mediated efflux constitutes an attractive means of potentially enhancing their therapeutic efficacy. The flavonoids comprise a large group of polyphenolic compounds that occur in plants and vegetables, and they have been shown to display a wide variety of biological activities. For example, anti-inflammatory, antioxidant, antiallergic, hepatoprotective, antithrombotic, antiviral, and anticarcinogenic activities. The interactions between flavonoids and Pgp have also been extensively studied and some quantitative structure-activity relationships (QSAR) have been reported. In the present work, we have employed 2D-QSAR analysis to evaluate the interactions between Pgp and several flavonoid compounds with the aim of identifying the molecular factors responsible for the Pgp-binding affinity evidenced by these compounds. Thus, the reported data for dissociation constants (KD) between Pgp and 62 flavonoid compounds were modeled by means of multiple regression analysis (MLR), and structures of the compounds under study were characterized by means of calculated physicochemical properties and several topological and constitutional descriptors, as well as geometrical and quantum chemical indexes. The obtained results suggest that the hydrophobic and especially geometric factors are of prime importance for binding, whereas in the case of flavonoid derivatives with flavone (flavonols), flavanone and isoflavone nuclei, the electronic factors are also involved in electron donor/acceptor interactions. In addition, in the case of chalcones, the results suggest that the affinity toward P-gp of such compounds is mainly governed by intermolecular dispersive interactions at the binding site.

Our goal was to address if intermittent hypobaric hypoxia (IHH) exposure can help to increase the number of peripheral blood circulating progenitor cells and side population (SP) stem cells, in order to establish the usefulness of this intervention for skeletal muscle repair, because these cells play a role in tissue regeneration. Male Sprague-Dawley rats were studied in two basal states: untrained and trained and compared with 1, 3, 7 and 14 days stages of damage recovery of trained rats that had suffered skeletal muscle injury. Three experimental groups were studied: rats with passive recovery (CTRL); rats exposed to IHH after muscle damage (HYP); and, trained rats that, in addition to IHH, performed light aerobic exercise sessions (EHYP). We observed an increase in hematopoietic stem cells (HSCs) (mean = 0.153% of cells) and endothelial progenitor cells (EPCs) (mean = 0.0020% of cells) in EHYP on day 7. Also these cells showed characteristics of more primitive progenitors in comparison to the other experimental groups (mean = 0.107% of cells), as deduced by retention of the promising fluorescent probe Vybrant Dye Cycle Violet. We concluded that intermittent exposure to hypobaric hypoxia in combination with light aerobic exercise increased the number of HSCs and EPCs on the 7th day in EHYP group, although the exercise-induced stimulus showed a reverse effect on SP kinetics.

The amyloidoses represent a group of diseases characterized by extracellular deposition of abnormal protein, amyloid, which is formed by insoluble extracellular fibrils in β-pleated sheets. Although cardiac involvement may occur in all types of amyloidoses, clinically relevant amyloid cardiomyopathy is a typical feature of AL amyloidosis and transthyretin-related amyloidoses. Congestive heart failure represents the commonest manifestation of amyloid heart disease. Noninvasive imaging techniques, especially echocardiography and cardiac magnetic resonance, play a major role in the diagnosis of amyloid cardiomyopathy; however, histological confirmation and exact typing of amyloid deposits is necessary whether in extracardiac location or directly in the myocardium. Early diagnosis of amyloid heart disease is of utmost importance as the presence and especially the severity of cardiac involvement generally drives the prognosis of affected subjects and plays a major role in determining the intensity of specific treatment, namely in AL amyloidosis. The management of patients with amyloid heart disease is complex. Loop diuretics together with aldosterone antagonists represent the basis for influencing signs of congestion. In AL amyloidosis, high-dose chemotherapy followed by autologous stem cell transplantation is generally considered to be a front-line treatment option, if the disease is diagnosed at its early stage. The combination of mephalan with dexamethasone has been the standard therapy for severely affected individuals; however, the combinations with several novel agents including immunomodulatory drugs and bortezomibe have been tested in clinical trials with promising results. New therapeutic substances with the potential to slow or even stop the progression of transthyretin-related amyloidosis are also extensively studied.

Diabetes is a chronic disease that affects over 400 million people globally. With 5.5% increase in diabetes re- lated deaths in 2010, as compared to the 2007 and World Health Organisation's projection of diabetes as the 7 th leading cause of death by 2030, has dazed the current drug discovery fraternity. The major focus of drug discovery has been to- wards the control of hyperglycemia while the severe complications arising due to it have been overlooked. Plant based natural products (pure phytochemicals or in the form of crude extracts) have been the mainstay of drug discovery program for treatment of numerous human diseases. In addition, indigenous systems of medicines like Ayurveda and Traditional Chinese Medicine (TCM) possess a rich plethora of knowledge about clinically used medicinal plants for controlling the diabetic complications. With India becoming the capital of diabetes and its associated complications, the present natural products perspective is more evident and highlights the current natural products based research that has been done for the last five years in tackling diabetic complications.

Herbs help in healing and treating the root cause of the ailment by rejuvenating the system in protecting from chronic diseases like Diabetes thus helping in leading a better quality of life, hence this study is aimed at comparing the quality of life assessment of patients taking herbal medicine and allopathic medicine using generic and disease specific tools (SF-36-V2- Short form health survey and QOLID (Quality of life of Indian Diabetic Patients))which helped in iden- tifying the influence of various life domains in diabetic patients and a better understanding of the treatment goal of herbs in diabetes. Significant difference in the outcomes scores in between treatment groups, indicate that herbal treatment is far better in terms of quality of life of specific domains VT (Vitality), BP (Bodily Pain), MH (Mental Health), GH (General Health) and PF (Physical Functioning) compared to the allopathic treatment.

This paper focuses on the physical property prediction of waste cooking oil biodiesel and examines the accuracy of different methods to estimate reliable basic physical properties, including density, viscosity and surface tension of waste cooking oil biodiesel in a wide range of temperature based on its fatty acid methyl ester component. A program for the physical property prediction of the biodiesel was developed and experimental measurements for the density, viscosity and surface tension of the biodiesel were performed to validate the chosen methods. The results show that the modified Rackett equation and the Orrick-Erbar method have the high estimation accuracy for the prediction of the density and the viscosity, respectively. The Sastri-Rao method and the Pizer method have the accuracy enough to predict the surface tension.

GNE (UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase) is a bifunctional enzyme which catalyzes the conversion of UDP-GlcNAc to ManNAc and ManNAc to ManNAc 6-phosphate, key steps in the sialic acid biosynthesis. Mutations in GNE lead to a neuromuscular disorder, Hereditary Inclusion Body Myopathy (HIBM). A major limitation in understanding the function of GNE is lack of recombinant full length GNE (rGNE) protein for detailed biophysical and structural characterization. In the present study, we have used Dictyostelium discoideum (Dd) as an alternate host for successful expression and secretion of functionally active form of GNE and its mutant proteins. We have generated Dd-AX3 stable cell lines harboring wtGNE or its mutants with Dd specific secretory signal sequence, PsA (prespore antigen). Upon starvation, rGNE was secreted in the medium from secretory vesicles. The rGNE was functionally active with epimerase activity (54±5.2 mU/mg) and kinase activity (66.45±3.48 mU/mg), while both epimerase and kinase activities of mutant GNE were drastically reduced. These activities were found to be statistically significant at p value < 0.05. Our study clearly demonstrates that Dd can be used as an expression host for the production of recombinant and functionally active form of GNE and its mutant proteins that can be used for biophysical characterization and structural determination of GNE to understand the pathomechanism of HIBM.

Rheum tanguticum, a source plant for the traditional Chinese medicine Dahuang (rhubarb), is an endangered species. In this study, we first assessed genetic diversity using 102 internal transcribed spacer (ITS) sequences cloned from one population of R. tanguticum on the Qinghai-Tibet Plateau. In total, 1773 polymorphic sites were identified, including 707 sites in the ITS1 region, 773 sites in the ITS2 region, and 293 sites on the 5.8S gene. Overall, transitions were the most common type of mutation and represented 77% of all base substitutions found within the ITS regions of R. tanguticum. We found that the average intra-specific genetic distance was 0.1260±0.0755 and ranged from 0 to 0.3618. Furthermore, a neighbor-joining phylogenetic tree constructed using these sequences strongly supported the conclusion that abundant intra-specific variation exists within the ITS regions of R. tanguticum. Interestingly, we found that eightyseven clones of R. tanguticum had high similarity to the ITS sequence of R. rhabarbarum and ten clones had high similarity to the ITS sequence of R. officinale; however, five clones of R. tanguticum had similarity to Fagopyrum esculentum. Therefore, we observed a significant amount of ITS sequence variation at both the intra-genomic and intra-specific levels in R. tanguticum. Based on these results, we suggest that in situ conservation is preferable for R. tanguticum protection.

The plastic reconstruction of the nose after microscopically controlled tumor surgery poses a particular challenge. The single pedicled nasalis myocutaneous flap is suited for the repair of defects of the distal nose. The flap is characterized by great tissue mobility and ensured vascular supply. Below a case study is presented that involves 4 patients who were treated with this special flap in our hospital after excision of a basal cell carcinoma. The scar quality was measured after one year with the scar assessment tool POSAS (The Patient and Observer Scar Assessment Scale). The single pedicled nasalis myocutaneous flap healed without any complication in all 4 patients. The nose shape could be preserved by the almost tension-free shift of the flap on the myocutaneous pedicle. The evaluation with the POSAS showed good results for all individual parameters and in the overall assessment. The single pedicled nasalis myocutaneous flap offers a good alternative to repair defects on the distal nasal bridge, nasal ala and the nasal tip. The pedicle provides a maximum on mobility combined with a good perfusion of the flap. As the flap is built out of nose tissue the color and texture can be kept which leads to an excellent cosmetic result. The good results are also reflected by the evaluation of the POSAS data.