l-Carnitine mediates protection against DNA damage in lymphocytes of aged rats

It has been proposed that age-associated disorders are related to a time-dependent shift in the antioxidant/prooxidant balance towards oxidative damage. Increased production of oxidants in vivo can cause damage to intracellular macromolecules such as DNA, proteins and lipids, which can in turn lead to oxidative injury. Carnitine is a vitamin-like compound that serves as a carrier to transport long-chain fatty acids into the mitochondria for β-oxidation. In the present study, the effect of l-carnitine, a widely recognized essential nutrient, was evaluated on the status of lipid peroxidation and certain antioxidant enzymes and DNA damage in lymphocytes with relation to age in male wistar rats. The levels of lipid peroxides were remarkably increased whereas, the activities of antioxidant enzymes were significantly decreased in aged control animals when compared to younger controls. In aged animals, administration of l-carnitine for 21 days significantly decreased the levels of lipid peroxides and improved the activities of antioxidant enzymes like superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. l-Carnitine enhanced T-cell proliferative responses as evaluated by T-cell proliferation assay using [³H] thymidine incorporation and also significantly reduced DNA damage, apoptosis and TNF-α level in lymphocytes of aged animals. Our results suggest that l-carnitine may have a vital role in improving functions in the cells of the immune system particularly the lymphocytes possibly through its antioxidant action.     

Attenuation of store-operated Ca2+ current impairs salivary gland fluid secretion in TRPC1(-/-) mice

Agonist-induced Ca(2+) entry via store-operated Ca(2+) (SOC) channels is suggested to regulate a wide variety of cellular functions, including salivary gland fluid secretion. However, the molecular components of these channels and their physiological function(s) are largely unknown. Here we report that attenuation of SOC current underlies salivary gland dysfunction in mice lacking transient receptor potential 1 (TRPC1). Neurotransmitter-regulated salivary gland fluid secretion in TRPC1-deficient TRPC1(-/-) mice was severely decreased (by 70%). Further, agonist- and thapsigargin-stimulated SOC channel activity was significantly reduced in salivary gland acinar cells isolated from TRPC1(-/-) mice. Deletion of TRPC1 also eliminated sustained Ca(2+)-dependent potassium channel activity, which depends on Ca(2+) entry and is required for fluid secretion. Expression of key proteins involved in fluid secretion and Ca(2+) signaling, including STIM1 and other TRPC channels, was not altered. Together, these data demonstrate that reduced SOC entry accounts for the severe loss of salivary gland fluid secretion in TRPC1(-/-) mice. Thus, TRPC1 is a critical component of the SOC channel in salivary gland acinar cells and is essential for neurotransmitter-regulation of fluid secretion.     

Association of Tumor Necrosis Factor-Alpha Gene Promoter Polymorphisms with Acute Viral Hepatitis in the Indian Population

The key elements that determine the host response to either the self-limited or a severe fulminant form of liver disease are unclear. We have investigated the potential association of single nucleotide polymorphisms (SNPs) in the promoter region of tumor necrosis factor-alpha (TNFα) in their susceptibility to acute viral hepatitis (AVH) and fulminant hepatic failure (FHF) patients exhibiting specific viral etiology. A total of 124 individuals including 64 cases comprising 27 FHF, 37 AVH, and 60 healthy controls were recruited. SNPs at −238 (G/A), −308 (G/A), −857 (C/T), and −863 (C/A) of TNFα were detected by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) and confirmed by direct sequencing. Serum levels of TNFα were determined at admission and death or recovery. Association between the TNFα genotype and susceptibility to FHF was not evident; however, carrier genotypes in relation to the −308 (GA/AA) and −857 (CT/TT) loci were found to be significantly (P ≤ 0.05) associated with susceptibility to AVH in relation to controls. The mean TNFα serum levels at admission were significantly higher (P < 0.001) in FHF than AVH patients, but no marked difference was observed between FHF-E (expired; n = 17) and FHF-S (survivors; n = 10), though the former were comparatively higher. This study suggests that SNPs at −308 and −857 of the TNFα promoter may represent an increased risk for the development of AVH but not for FHF in the Indian population.     

Circumferential Stent Fracture: novel detection and treatment with the use of StentBoost

Circumferential stent fracture is extremely uncommon, and in rare cases, it can cause stent thrombosis. Recognizing stent fracture can be difficult on conventional fluoroscopy because of poor stent radiopacity. We found that StentBoost image acquisition yields improved visibility of stent struts, enabling the identification of stent fracture and the precise positioning of new stents over previously stented segments.We report the case of a 50-year-old man who presented with acute myocardial infarction and subacute stent thrombosis a week after percutaneous transluminal coronary angioplasty and placement of a bare-metal stent. The new lesion was crossed with a guidewire, but multiple attempts to advance a balloon catheter were unsuccessful. Live StentBoost image acquisition revealed circumferential stent fracture into 2 separate sections, with abnormal angulation between the proximal and distal portions of the stent. With StentBoost guidance, the wire and balloon catheter were both easily manipulated to cross the lesion, and angioplasty and restenting were completed with good results.StentBoost can be a useful adjunctive tool for the cardiac interventionist during complex percutaneous transluminal coronary angioplasty, and it was invaluable in this challenging situation. We discuss stent fracture and the benefits of using StentBoost in such situations.     

Transplacentally transferred functional antibodies against Plasmodium falciparum decrease with age

Transplacental transfer of antibodies from clinically malaria immune pregnant women to their fetuses is thought to provide passive protection against malaria during infancy. However, the presences and duration of functional antibodies against Plasmodium falciparum (Pf) in newborns has not been described. We used growth inhibition assays (GIA) to measure total anti-malaria functional antibodies present at birth and over the following year. Samples were drawn from cord blood (n = 86) and in infants at six and 12 months of life (n = 86 and 65 respectively). Three laboratory Pf strains (D10, W2mef, 3D7) and a field isolate (Msambweni 2006) were used in the assays. Median (ranges) GIA levels for cord plasma differed between laboratory parasite strains: D10, 0% (0–81); W2mef, 6% (0–80); 3D7, 18% (0–88); Msambweni 2006, 6% (0–43) (P < 0.001, Wilcoxon signed-rank test). GIA levels against all Pf strains were found to decline in infants from birth to six months (P < 0.01, Wilcoxon, signed-rank test). Functional antibodies as measured by GIA are transferred to the fetus and wane in the infants over time. Infant protection from clinical malaria disease may in part be mediated by these functional anti-malaria antibodies.     

Mosquito larvicidal and pupicidal activity of Euphorbia hirta Linn. (Family: Euphorbiaceae) and Bacillus sphaericus against Anopheles stephensi Liston. (Diptera: Culicidae)

ObjectiveTo explore the larvicidal and pupicidal activity of Euphorbia hirta (E. hirta) leaf extract and Bacillus sphaericus (B. sphaericus) against the malarial vector, Anopheles stephensi (An. stephensi).MethodsThe larvicidal and pupicidal activity was assayed against An. stephensi at various concentrations ranging from (75-375 ppm) under the laboratory as well as field conditions. The LC₅₀ and LC₉₀ value of the E. hirta leaf extract was determined by probit analysis.ResultsThe plant extract showed larvicidal effects after 24 h of exposure; however, the highest larval mortality was found in the methanol extract of E. hirta against the first to fourth instars larvae and pupae of values LC₅₀= 137.40, 172.65, 217.81, 269.37 and 332.39 ppm; B. sphaericus against the first to fourth instars larvae and pupae of values LC₅₀= 44.29, 55.83, 68.51, 82.19 and 95.55 ppm, respectively. Moreover, combined treatment of values of LC₅₀= 79.13, 80.42, 86.01, 93.00 and 98.12 ppm, respectively. No mortality was observed in the control.ConclusionsThese results suggest methanol leaf extracts of E. hirta and B. sphaericus have potential to be used as an ideal eco-friendly approach for the control of the malarial vector, An. stephensi as target species of vector control programs. This study provides the first report on the combined mosquito larvicidal and pupicidal activity of this plant crude extract and bacterial toxin against An. stephensi mosquitoes.     

Pycnodysostosis with visceral manifestation and rickets

Pycnodysostosis is a rare bone disease. Visceral manifestations associated with anemia and/or rickets have been reported in pycnodysostosis. Five children with typical findings of pycnodysostosis with hepatosplenomegaly, anemia with rickets, one with visceromegaly and anemia, and another with rickets alone are reported here. These findings strongly suggest that extramedullary erythropoiesis does occur in pycnodysostosis.     

Tuberculosis subunit vaccine design: the conflict of antigenicity and immunogenicity

The attempts to find an effective antituberculous subunit vaccine are based on the assumption that it must drive a Th1 response. In the absence of effective correlates of protection, a vast array of mycobacterial components are being evaluated worldwide either on the basis of their ability to be recognized by T lymphocytes in in vitro assays during early stage of animal or human infection (antigenicity) or their capacity to induce T cell response following immunization in animal models (immunogenicity). The putative vaccine candidates selected using either of these strategies are then subjected to challenge studies in different animal models to evaluate the protective efficacy. Here we review the outcome of this current scheme of selection of vaccine candidates using an 'antigenicity' or 'immunogenicity' criterion on the actual protective efficacy observed in experimental animal models. The possible implications for the success of some of the leading vaccine candidates in clinical trials will also be discussed.     

MoS2 nanosheet mediated ZnO–g-C3N4 nanocomposite as a peroxidase mimic: catalytic activity and application in the colorimetric determination of Hg(ii)

A novel colorimetric sensing platform using the peroxidase mimicking activity of ternary MoS₂-loaded ZnO–g-C₃N₄ nanocomposites (ZnO–g-C₃N₄/MoS₂) has been developed for the determination of Hg(ii) ions over co-existing metal ions. The nanocomposite was prepared using an exfoliation process, and the product was further characterized using SEM, TEM, XRD and FTIR analysis. The ZnO–g-C₃N₄/MoS₂ possesses excellent intrinsic catalytic activity to induce the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) in aqueous solution in the presence of H₂O₂ to generate deep blue coloured cation radicals (TMB⁺) which can be viewed with the naked eye and produce absorbance at a wavelength of 652 nm. The addition of a well known bioradical scavenger, glutathione (GSH), to the solution hinders the generation of cation radicals and turns the solution colourless. The introduction of Hg(ii) to this solution brings the blue colour back into it, due to the strong affinity of the thiol in the GSH. Based on this mechanism, we have developed a simple and rapid colorimetric sensor for the highly sensitive and selective detection of Hg(ii) ions in aqueous solution with a low detection limit of 1.9 nM. Furthermore, the prepared colorimetric sensor was effectively applied for the quantification analysis of real water samples.

A novel colorimetric sensing platform using the peroxidase mimicking activity of ternary MoS₂-loaded ZnO–g-C₃N₄ nanocomposites (ZnO–g-C₃N₄/MoS₂) has been developed for the determination of Hg(ii) ions over co-existing metal ions.