Waste management - cytokines, growth factors and cachexia

Muscle damage with a lack of regeneration, manifests itself in several life-threatening diseases, including cancer cachexia, congestive heart failure, AIDS and sepsis. Often misdiagnosed as a condition simply of weight loss, cachexia is actually a highly complex metabolic disorder involving features of anorexia, anaemia, lipolysis and insulin resistance. A significant loss of lean body mass arises from such conditions, resulting in wasting of skeletal muscle. Unlike starvation, the weight loss seen in chronic illnesses arises equally from loss of muscle and of fat. The cachectic state is particularly problematic in cancer, typifying poor prognosis and often lowering responses to chemotherapy and radiation treatment. More than half of cancer patients suffer from cachexia, and strikingly, nearly one-third of cancer deaths are related to cachexia rather than the tumour burden. In considering this disorder, we are faced with a conundrum; how is it possible for uncontrolled growth to prevail in the tumour, in the face of unrestrained tissue loss in our muscles? Consistently, the catabolic state has been associated with a shift in the homeostatic balance between muscle synthesis and degradation mediated by the actions of growth factors and cytokines. Indeed, tumour necrosis factor-alpha (TNF-alpha) levels are raised in several animal models of cachectic muscle wasting, whereas the insulin-like growth factor (IGF) system acts potently to regulate muscle development, hypertrophy and maintenance. This concept of skeletal muscle homeostasis, often viewed as the net balance between two separate processes of protein synthesis and degradation has however changed. More recently, the view is that these two biochemical processes are not occurring independently of each other but in fact are finely co-ordinated by a web of intricate signalling networks. This review, therefore, aims to discuss data currently available regarding the mechanisms of degeneration and regeneration with specific emphasis on the potential and controversial cross-talk which may exist between anabolic growth factors (e.g. IGF-I) and catabolic cytokines (e.g. TNF-alpha). Also importantly, the potential impact at a cellular level of exercise, diet and age will be addressed. Finally, the ability to 'hi-jack' signalling pathways traditionally believed to be for growth and survival or death will be reviewed. It is anticipated that such a review will highlight significant gaps in our knowledge of the cachectic state as well as provide caution with regards to therapeutics suggesting total block on inflammatory processes such as that associated with TNF-alpha action.     

Identification of RAPD markers linked to the karnal bunt resistance genes in wheat

A set of 104 wheat recombinant inbred lines (RILs) obtained from a cross between parents resistant (HD 29) and susceptible (WH 542) to karnal bunt (KB) (caused by Neovossia indica) were screened and used to identify random amplified polymorphic DNA (RAPD) markers linked with resistance to karnal bunt as these would allow indirect marker assisted selection of KB resistant genotypes. The two parents were analysed with 92 RAPD primers. A total of 65 primers proved functional by giving scorable polymerase chain reaction (PCR) products. Of these, 21 (32 %) primers detected polymorphism between the two parental genotypes. Using these primers, bulked segregant analysis was carried out on two bulk DNAs, one obtained by pooling DNA from 10 KB resistant RILs and the other similarly derived by pooling 10 KB susceptible RILs. One marker, OPM-20 showed apparent association with resistance to KB. This was confirmed following selective genotyping of individual RILs included in the bulks.     

Neuroprotective Effects of Bacopa monnieri in Experimental Model of Dementia

Alzheimer disease (AD) is characterized by dementia that begins as mild short term memory deficit and culminates in total loss of cognitive and executive functions. The present study was conducted to evaluate the neuroprotective potential of Bacopa monnieri (BM), an Indian traditional medicinal plant effective against cognitive impairment, in colchicine-induced dementia. Intracerebroventricular administration of colchicine (15?μg/5?μl) induced cognitive impairment in rats as assessed by elevated plus maze. This was accompanied by a significant increase in oxidative stress in term of enhanced levels of lipid peroxidation and protein carbonyls. Concomitantly, decrease in activity of antioxidant enzymes was observed in colchicine treated animals. BM (50?mg/kg body weight) supplementation reversed memory impairment observed in the colchicine treated rats. BM administration attenuated oxidative damage, as evident by decreased LPO and protein carbonyl levels and restoration in activities of the antioxidant enzymes. The activity of membrane bound enzymes (Na(+)K(+) ATPase and AChE) was altered in colchicine treated brain regions and BM supplementation was able to restore the activity of enzymes to comparable values observed in controls. The results suggest therapeutic potential of BM in the treatment of AD associated cognitive decline.     

Identification of Contact Sites between Ankyrin and Band 3 in the Human Erythrocyte Membrane

The red cell membrane is stabilized by a spectrin/actin-based cortical cytoskeleton connected to the phospholipid bilayer via multiple protein bridges. By virtue of its interaction with ankyrin and adducin, the anion transporter, band 3 (AE1), contributes prominently to these bridges. In a previous study, we demonstrated that an exposed loop comprising residues 175-185 of the cytoplasmic domain of band 3 (cdB3) constitutes a critical docking site for ankyrin on band 3. In this paper, we demonstrate that an adjacent loop, comprising residues 63-73 of cdB3, is also essential for ankyrin binding. Data that support this hypothesis include the following. (1) Deletion or mutation of residues within the latter loop abrogates ankyrin binding without affecting cdB3 structure or its other functions. (2) Association of cdB3 with ankyrin is inhibited by competition with the loop peptide. (3) Resealing of the loop peptide into erythrocyte ghosts alters membrane morphology and stability. To characterize cdB3-ankyrin interaction further, we identified their interfacial contact sites using molecular docking software and the crystal structures of D(3)D(4)-ankyrin and cdB3. The best fit for the interaction reveals multiple salt bridges and hydrophobic contacts between the two proteins. The most important ion pair interactions are (i) cdB3 K69-ankyrin E645, (ii) cdB3 E72-ankyrin K611, and (iii) cdB3 D183-ankyrin N601 and Q634. Mutation of these four residues on ankyrin yielded an ankyrin with a native CD spectrum but little or no affinity for cdB3. These data define the docking interface between cdB3 and ankyrin in greater detail.     

Discrepancies in identification of Vibrio cholerae strains as members of Aeromonadaceae and Enterobacteriaceae by automated microbial identification system

Aims: Incidental observation of a discrepancy in identification of Vibrio cholerae prompted a study to understand the ability of an automated microbial identification system to identify this important pathogen. Methods and Results: Twenty clinical isolates of V. cholerae showing difference in genetic profiles by random amplified polymorphic DNA (RAPD) fingerprinting, serologically confirmed as O1, and showing presence of ctxA and tcpA genes in PCR were subjected to analysis by Vitek 2 Compact automated identification system for identification. Vitek 2 Compact detected 10 of 20 isolates correctly, whereas the remaining 10 were identified as various members of Aeromonadaceae and Enterobacteriaceae. Conclusions: Our results indicate that Vitek 2 Compact automated microbial system does not always identify V. cholerae strains correctly. Significance and Impact of Study: These observations should create awareness among end users about possible misidentifications by automated systems and encourage simultaneous use of serology and/or PCR for correct identification at least for V. cholerae, which is one of the most important enteric pathogens.     

Surfactant mediated enhanced biodegradation of hexachlorocyclohexane (HCH) isomers by Sphingomonas sp. NM05

Environmental biodegradation of several chlorinated pesticides is limited by their low solubility and sorption to soil surfaces. To mitigate this problem we quantified the effect of three biosurfactant viz., rhamnolipid, sophorolipid and trehalose-containing lipid on the dissolution, bioavailability, and biodegradation of HCH-isomers in liquid culture and in contaminated soil. The effect of biosurfactants was evaluated through the critical micelle concentration (CMC) value as determined for each isomer. The surfactant increased the solubilization of HCH isomers by 3-9 folds with rhamnolipid and sophorolipid being more effective and showing maximum solubilization of HCH isomers at 40 μg/mL, compared to trehalose-containing lipid showing peak solubilization at 60 μg/mL. The degradation of HCH isomers by Sphingomonas sp. NM05 in surfactant-amended liquid mineral salts medium showed 30% enhancement in 2 days as compared to degradation in 10 days in the absence of surfactant. HCH-spiked soil slurry incubated with surfactant also showed around 30-50% enhanced degradation of HCH which was comparable to the corresponding batch culture experiments. Among the three surfactants, sophorolipid offered highest solubilization and enhanced degradation of HCH isomers both in liquid medium and soil culture. The results of this study suggest the effectiveness of surfactants in improving HCH degradation by increased bioaccessibility.     

Autoimmune thyroid disease in patients with vitiligo: prevalence study in India

ObjectiveTo identify the prevalence of autoimmune thyroid disease (AITD) in Asian Indian patients with vitiligo and to compare the clinical profile between thyroid peroxidase (TPO) antibody-positive and TPO antibodynegative groups.MethodsIn this cross-sectional, case-controlled study, 50 patients with vitiligo (29 women and 21 men) were included. Patients with previous disorders, irradiation, or surgical procedures involving the thyroid were excluded from the study. All participants underwent a complete physical examination, and a single fasting blood sample was analyzed for thyroid function (triiodothyronine, thyroxine, thyroid-stimulating hormone, and TPO and thyroglobulin antibodies), inflammatory and immunologic markers (erythrocyte sedimentation rate, C-reactive protein, and rheumatoid factor), and serum calcium, phosphorus, and alkaline phosphatase concentrations. All patients underwent thyroid ultrasonography, and the data were analyzed by appropriate statistical methods.ResultsThe mean age of the study participants was 42.7 ± 17 years, and 14 of 50 patients (28%) had TPO antibody positivity. A goiter was present in 11 of 50 patients, and the thyroid volume by ultrasonography was similar between the 2 groups. Subclinical hypothyroidism was found in 14 of 50 patients (28%) but more frequently in the TPO antibody-positive group (8 of 14 or 57%) than in the TPO antibody-negative group (6 of 36 or 17%). The prevalence of AITD was 20 of 50 patients (40%) when the TPO antibody-positive group and those with subclinical hypothyroidism were considered collectively. None of the patients had overt hypothyroidism or hyperthyroidism. All other clinical, biochemical, and inflammatory variables did not differ significantly between the TPO antibody-positive and antibody-negative groups.ConclusionOur data showed a 40% prevalence of thyroid disease in patients with vitiligo in India. The risk is exacerbated in patients with thyroid autoimmunity; thus, regular screening of patients with vitiligo for AITD is needed. (Endocr Pract. 2012;18:194-199)