Hydrogen sulphide: an emerging regulator of plant defence signalling.

Hydrogen sulphide (H2 S), a gaseous signalling molecule in plants, has gained considerable attention in recent years because of its emerging roles in the regulation of plant growth and development and responses to abiotic stressors. Although the involvement of H2 S in biotic stress is not well documented in the literature, a growing body of evidence indicates its potential role in plant defence, particularly against bacterial and fungal pathogens. Recent reports have suggested that H2 S participates in plant defence signalling potentially by (1) regulating glutathione metabolism, (2) inducing expression of pathogenesis-related (PR) and other defence-related genes, (3) modulating enzyme activity through post-translational modifications, and (4) interacting with phytohormones such as jasmonic acid, ethylene and auxin. In this review, we discuss the biosynthesis, metabolism and interaction of H2 S with phytohormones, and highlight evidence gathered so far to support the emerging roles of H2 S in plant defence against invading pathogens.

Over-the-counter medicines: Global perspective and Indian scenario.

Patients often approach a pharmacist instead of visiting a doctor for minor ailments such as cough, cold, allergies, pain, fever, acidity, diarrhea, and skin-related conditions. Purchase of specific medicines over the counter is legally recognized in most countries. 'Over-the-Counter (OTC) Medicines' means drugs which are legally allowed to be sold by pharmacists without need for a prescription. The term does not have a legal definition in India. Technically, drugs are OTC unless they are specifically stated as prescription only drugs. OTC drugs allow faster and cheaper access to healthcare; however, their misuse and adverse health effects cause concerns. This article describes concept of OTC medicines and practices in India against the background of globally prevalent regulations and practices. A recognized category of OTC medicines by law, patient awareness programs, and support of pharmacists and pharmaceutical companies are required to optimize the use of OTC medicines in India.

Lenalidomide as a novel therapy for gastrointestinal angiodysplasia in von Willebrand disease.

INTRODUCTION: Lenalidomide is a thalidomide analog with anti-angiogenic properties. Previous case reports suggest its efficacy in preventing gastrointestinal bleeding (GIB) secondary to angiodysplasia (AD) in hereditary haemorrhagic telangiectasia and potentially in reversing AD. We present the first case series to explore lenalidomide as a treatment for AD-related GIB in patients with von Willebrand disease (VWD). METHODS: A retrospective chart review was conducted to include patients with VWD, who were evaluated from 2010 to 2013 and who had received lenalidomide to treat recurrent GIB secondary to AD. All patients had failed single-agent use of antifibrinolytic agents. Patients were observed for at least 2 years on therapy. RESULTS: Five patients (3 males; 68.2 ± 4.9 years) with VWD (3 with type 3 and 1 each with types 1 and 2a) and AD were found. Sites of AD included the stomach, duodenum, jejunum and colon. Lenalidomide was started at 5 mg oral daily. Uptitration to 10 and 15 mg in 1 patient each was necessary due to recurrence of GIB. The mean number of endoscopies performed for control of GIB post lenalidomide was significantly lower compared to pretherapy (0.25 vs 5.50; P = .001). Mean bleed-free duration on lenalidomide was 12.6 ± 4.7 months. Three patients have reported no GIB on lenalidomide. CONCLUSION: This case series demonstrates significantly reduced number of endoscopies and increased bleed-free duration with lenalidomide treatment in selected patients with VWD and recurrent GIB from AD. Prospective multicenter trials are needed to further define the role of lenalidomide in the management of GIB from angiodysplasia and VWD.

Role of moving average analysis for development of multi-target (Q)SAR models.

In modern drug discovery era, multi target- quantitative structure activity relationship [mt- (Q)SAR] approaches have emerged as novel and powerful alternatives in the field of in-silico drug design so as to facilitate the discovery of new chemical entities with multiple biological activities. Amongst various machine learning approaches, moving average analysis (MAA) has frequently exhibited high accuracy of prediction of diverse biological activities against different biological targets and experimental conditions. Role of MAA in developing (Q)SAR models for prediction of single/dual or multi target activity has been briefly reviewed in the present article. Subsequently, MAA was successfully utilized for developing mt-(Q)SAR models for simultaneous prediction of anti-Plasmodium falciparum and anti-Trypanosoma brucei rhodesiense activities of benzyl phenyl ether derivatives. The statistical significance of models was assessed through intercorrelation analysis, sensitivity, specificity and Matthew's correlation coefficient. Proposed MAA based models were also validated using test set. High predictability of the order of 80% to 95% amalgamated with safety (indicated by high value of selectivity index) of proposed mt-(Q)SAR models justifies use of MAA in developing models in order to obtain more realistic and accurate results for prediction of anti-protozal activity against multiple targets. Active ranges of the proposed models can play a significant role in the development of novel, potent, versatile and safe anti-protozoal drugs with improved profile in terms of both anti-Plasmodium falciparum and anti-Trypanosoma brucei rhodesiense activities.

In vivo delivery aspects of miRNA, shRNA and siRNA.

RNA interference (RNAi) is a wondrous phenomenon that silences the expression of targeted genes via distinct messenger RNA degradation pathways. It has the potential as a therapeutic agent for variety of diseases, including viral infections, cancer, and immune diseases. RNAi mainly conducts gene regulation by 3 ways: microRNA, short hairpin RNA, and small interfering RNA. However, in vivo delivery of RNAi therapeutics is restricted because of charge density, molecular weight, and instability in the presence of nucleases. Furthermore, intracellular accumulation and endosomal escape have remained significant barriers in the delivery of these macromolecules. Many viral and nonviral delivery vectors have been thoroughly investigated to overcome these barriers. Researchers have found applications for RNAi in a variety of diseases and, hence, various delivery systems have been explored to satisfy the need. Both local and systemic strategies have been utilized to elicit RNAi's effect and each carries its own therapeutic implications with varying margins of safety. This review is an effort to describe the types of RNAi and their application in a variety of diseases using both local and systemic delivery approaches. It is sure that advancement in this direction will evolve a new landscape for treating a range of diseases.

Development of siRNA lipoplexes for intracellular delivery in lung cancer cells.

Lung cancer occurrence throughout the world and its unsatisfactory treatment has drawn significant attention from many medical agencies. A genomic approach utilizing siRNA against target gene may resolve this problem. Present investigation includes siRNA lipoplex formulation and its in-vitro characterisation in lung cancer cell line for intracellular uptake and cytotoxicity. Accumulation of siRNA inside the cell as well as less cytotoxicity of prepared carrier system signifies potential of prepared siRNA lipoplex in the treatment of lung cancer.

Clinical profiles of 13 children with Plasmodium vivax cerebral malaria.

BACKGROUND: Bikaner region is endemic for both P. vivax and P. falciparum malaria. Usually, cerebral malaria is caused by P. falciparum but it has been reported recently also in P. vivax mono-infection. Epidemiologic studies and clinical descriptions of P. vivax cerebral malaria in children are rare. AIMS: To describe the clinical features of PCR-confirmed cerebral malaria owing to P. vivax mono-infection and its clinico-laboratory profile in Bikaner, Northwest India. METHODS: This observational prospective study was based on detailed clinical and laboratory investigation of children admitted with cerebral malaria owing to P. vivax between November 2008 and December 2010. Cerebral malaria was categorised according to the WHO (2000) criteria for P. falciparum and the diagnosis of P. vivax mono-infection was established by peripheral blood film and rapid diagnostic tests and confirmed by polymerase chain reaction. The possibility of other diseases/infections causing similar illness were investigated thoroughly. RESULTS: Thirteen children with P. vivax cerebral malaria were studied, eight of whom (61·5%) had multi-organ (two or more organs) dysfunction. Other associated severe manifestations included severe anaemia (7), hepatic dysfunction (2), renal dysfunction (2), bleeding manifestation (2), respiratory distress (2), metabolic acidosis (2) and shock (one). Hypoglycaemia was not observed in any patient. There was no evidence of neurological sequelae. All the children were managed according to WHO guidelines using intravenous artisunate. Thrombocytopenia was detected in five and hyponatraemia in four children. CONCLUSION: P. vivax mono-infection can cause cerebral malaria and multi-organ dysfunction.

Synthesis and mechanical properties of interconnected carbon nanofiber network reinforced polydimethylsiloxane composites.

Carbon nanofiber (CNF) reinforced elastomer composites with light weight, sustainability of large deformation, chemical stability, corrosion and fatigue resistance, and vibration and noise reduction capability can have positive impact on a wide range of applications. However, this type of composite is still a under studied research area due to the difficulties in material handling and processing. To improve processing control and reproducibility for large scale engineering applications, cost effective carbon nanofibers (CNFs) in form of interconnected porous network structure were used as nanofillers. Processing, microstructure and mechanical properties of carbon nanofibers reinforced polydimethylsiloxane (PDMS) have been studied. Mechanical measurements on the composites show that the CNF-PDMS interfacial bonding can be until failure, interfacial debonding happens in the CNF-PDMS composites and the resulted permanent deformation stabilizes with increasing load-unload cycles with significant energy dissipation.

Impact of field vaccination with a Theileria annulata schizont cell culture vaccine on the epidemiology of tropical theileriosis.

Tropical theileriosis, caused by Theileria annulata, is an important tick-borne disease of cattle. A cell culture attenuated vaccine has been developed in our laboratory by long-term in vitro propagation of the schizont stage of the parasite. A longitudinal study was conducted at selected farms housing indigenous, cross-bred and exotic animals to investigate the effect of vaccination on the epidemiology of the disease. A total of 120 animals in 4 age groups were vaccinated with the vaccine before the onset of disease season. An equal number of age-matched animals were kept as controls at the same sites. Animals were monitored for 14 months at monthly intervals. The 97.5% vaccinated animals showed a rise in antibody titres 1 month post-vaccination, as determined by single dilution ELISA. The 78.3% of non-vaccinated animals became sero-positive over the period of observation. Mean antibody titres were significantly higher in vaccinated than non-vaccinated animals. Cross-bred animals showed higher antibody titres followed by exotic and indigenous animals in both the vaccinated and non-vaccinated groups. However, the antibody titres in animals of different ages were similar. The 36.7% vaccinated and 64.2% non-vaccinated animals became carriers (<0.5% piroplasms in erythrocytes) during the observation period. Clinical cases of theileriosis were recorded only in the non-vaccinated group suggesting that vaccinated animals were sufficiently immune to withstand field tick challenge for at least 14 months.

Effect of vaccination in the field with the Theileria annulata (Hisar) cell culture vaccine on young calves born during the winter season.

The responses were monitored of young crossbred calves vaccinated against tropical theileriosis during the winter against a field tick challenge in the disease season. Thirty-eight calves below 2 months of age, born after the end of the disease season, were selected at an organized farm. Twenty-five animals were vaccinated with Theileria annulata (Hisar) cell culture vaccine (developed at CCS HAU Hisar laboratory) after the end of the disease season and 13 calves were kept as non-vaccinated controls. These calves were observed for their susceptibility to theileriosis in the new disease season. There was an increase in antibody titre in 18 of the 25 vaccinated animals one month after vaccination. The antibody titre then declined gradually, but remained higher than those of the non-vaccinated animals at month 0. No fever or other clinical signs of tropical theileriosis were observed in any of the vaccinated animals. Nine out of 25 (36%) vaccinated calves showed occasional piroplasms (<0.5%) in blood smears. All the vaccinated animals withstood the field tick challenge. On the other hand, 9 of the 13 (69%) unvaccinated calves exhibited occasional piroplasms, and included three clinical cases of tropical theileriosis. These observations suggest that young crossbred calves vaccinated with the T. annulata (Hisar) cell culture vaccine at the end of the disease season were relatively resistant during the next disease season.

Validity of self-reports about quality of life among patients with schizophrenia.

Lehman's Quality of Life Interview was administered to 22 patients with schizophrenia and their proxies and to 15 patients with cancer and their proxies. The results indicated that there was a discrepancy between responses on global objective and subjective measures for patients with schizophrenia but not for patients with cancer. A discrepancy was also found for the proxies of the patients with schizophrenia but not for the proxies of the patients with cancer. These findings suggest that the discrepancy between subjective and objective indicators of quality of life of patients with schizophrenia signifies a genuine difference rather than an anomaly related to the patient's psychiatric condition.

Cognitive therapy: looking backward, looking forward.

This article reviews some of the historical factors associated with the unprecedented strength and popularity of cognitive therapy, and offers predictions for the next half-century of this approach to treatment. It is predicted that the future will bring with it increased demands on cognitive therapy for evaluation of processes of change (including identification of therapeutic specifics and nonspecifics, technical specification of the process of therapy, and examination of therapist and patient predictors of change), and accountability and efficiency in the public and private sectors. With the increase in personal autonomy, globalization, and technology, the demands from the general public also will increase. One possible risk of the trend towards increased technology is that cognitive therapy may become overly technical. Although specific therapy techniques are crucial to delivering effective treatment, it is also the "nonspecifics" of therapy that add to the "art" of psychotherapy. The final challenge of cognitive therapy also may be the most difficult--to continue to be an empirically based science while maintaining its role in the art of healing.

Gynecologic cytology from the perspective of the Laboratory Proficiency Testing Program, Ontario, Canada.

The accumulated test results from annual proficiency testing of approximately 150 cytology laboratories during the period 1977-1992 were analyzed. Several features of the test program are presented, including the adaptability of the uniform diagnostic terminology that was in use throughout. Observations include the impact of screening by a technologist; the better diagnostic performance generally, but not exclusively, in larger-volume laboratories; the degree of reproducibility of reporting in the laboratory; the ease of diagnosis in some diagnostic categories; and patterns observed in "false negative" and "false positive" rates. The follow-up analysis of suboptimal performance is recorded, and remedial and educational aspects are emphasized. The impact of levels of performance on the specific population being screened is correlated with the data on laboratory caseloads and with hospital vs. nonhospital laboratories.

NMR characterization of functional groups: 9--isomer ratios of available chloromethylstyrene mixtures.

From the assignments of the 1H and 13C 11.7 tesla NMR spectra of available mixtures of m- and p-chloromethylstyrene, the proportion of the meta and para compounds are easily determined. For these materials from two common commercial sources, proportions of 72 and 28% and 68 and 32% were found. These concentrations are substantially different from the often assumed 60 and 40% for the meta and para compounds, respectively. The influence of this difference on the desired properties of copolymers made from such mixtures is discussed. An alternative quantitative procedure for determining the chloromethyl group isomer ratios is also described which employs silver trifluoroacetate in acetone displacement of chloride and 19F NMR examination of the resulting ester mixture with a 2.3 tesla spectrometer.

Serum gonadotropins and testosterone in infertile patients with varicocele.

Serum concentrations of gonadotropins and testosterone in 25 infertile men with varicocele were compared with those in control men and men with idiopathic oligo-azoospermia. No significant difference was found in values of serum follicle-stimulating hormone (FSH) (14.9 +/- 13.6 mIU/ml), luteinizing hormone (LH) (24.9 +/- 19.1 mIU/ml), and testosterone (5.0 +/- 2.1 ng/ml) when the group with varicocele was compared with either the control group (FSH, 7.0 +/- 3.2 mIU/ml; LH, 23.6 +/- 16.0 mIU/ml; testosterone, 5.3 +/- 1.8 ng/ml) or the group with idiopathic oligo-azoospermia (FSH, 23.0 +/- 22.69 mIU/ml; LH, 36.7 +/- 24.1 mIU/ml; testosterone, 5.31 +/- 2.3 ng/ml). However, compared with the control group, there was a significant elevation of serum FSH levels in patients with varicocele whose testicular biopsy score counts were between 1 and 4. The importance of preoperative determination of the serum FSH level is discussed.