Serum levels of interleukin-13 and interferon-gamma from adult patients with asthma in Mysore

Serum protein analysis for noninvasive quantification of airway inflammation in asthma is a promising research tool in the field of lung diseases. Cytokines are believed to have major role in inflammatory process of the airways of the lung. There is an imbalance between T-helper (Th)-2 cells, which secrete interleukin (IL)-4 and interleukin (IL)-13, and Th1 cells, which secrete interferon (IFN)-gamma in asthma. To test the hypothesis that serum IL-13 and IL-4 levels may be elevated whereas IFN-gamma would be decreased in this cohort of patients, a property that could make them possible candidate biomarkers in determining asthma occurrence and severity, we measured concentrations of IL-4, IL-13 and IFN-gamma in serum samples of 88 subjects (44 normal, 12 with mild asthma, 16 with moderate asthma, and 16 with severe asthma). Serum Levels of IL-4, IL-13, and IFN-gamma were determined by an enzyme-linked immune-sorbent assay (ELISA). Median serum level of IFN-gamma in asthmatic patients was 8.0pg/ml, while it was 11.4pg/ml in healthy controls. However, the difference was not significant. Among the different age groups in whom IFN-gamma was assessed, the highest median value in both cases and controls was observed in the age group of 31-40years. The median serum level of IL-13 was 40.0pg/ml in asthmatic patients and 58.25pg/ml in healthy controls. The difference was not significant. On subgroup analysis, no significant difference of IFN-gamma and IL-13 between asthma of different severities was observed. The study also revealed nonsignificant difference of serum cytokines with the duration of asthma, number of allergens, and severity of sensitization. Normal serum levels of IFN-gamma and IL-13 in asthmatic patients suggest their neutral role in the inflammatory process; however, more studies are required to establish the effect of these cytokines in adulthood asthma in different ethnic populations.     

Olmesartan medoxomil treatment potently improves cardiac myosin-induced dilated cardiomyopathy via the modulation of ACE-2 and ANG 1-7 mas receptor

Angiotensin converting enzyme-2 (ACE-2) is a monocarboxypeptidase that metabolises angiotensin (ANG)-II into angiotensin 1-7 (ANG 1-7), thereby functioning as a negative regulator of the renin-angiotensin system. We investigated whether treatment with ANG-II type 1 receptor blocker, olmesartan medoxomil is associated with the attenuation of cardiac myosin-induced dilated cardiomyopathy (DCM) through recently established new axis of ACE-2/ANG 1-7 mas receptor. DCM was elicited in Lewis rats by immunisation with cardiac myosin, and 28 days after immunisation, the surviving Lewis rats were divided into two groups and treated with either olmesartan medoxomil (10 mg/kg/day) or vehicle. Myocardial protein and mRNA levels of ACE-2, ANG 1-7 mas receptor were upregulated in the olmesartan-treated group compared with those of vehicle-treated DCM rats. In contrast, Olmesartan treatment effectively suppressed the myocardial protein and mRNA expressions of inflammatory markers in comparison to the vehicle-treated DCM rats. Olmesartan treatment significantly reduced fibrosis, hypertrophy and their marker molecules (OPN, CTGF, ANP and GATA-4, respectively), as well as matrix metalloproteinases compared with those of vehicle-treated DCM rats. Enhanced myocardial protein levels of phospho-p38 MAPK, phospho-JNK and phospho MAPKAPK-2 in the vehicle-treated DCM rats were prevented by olmesartan treatment. In addition, olmesartan treatment significantly lowered the protein expressions (Nitrotyrosine, p47phox and p67phox) and superoxide radical production compared with those of vehicle-treated DCM rats. Our present study might serve as a new therapeutic target of DCM in cardiovascular diseases and cardiac myosin-induced DCM via the modulation of ACE-2/ANG 1-7 mas receptor axis in rats with DCM after myosin-immunisation.     

In vitro antibacterial activity of Psidium guajava Linn. leaf extract on clinical isolates of multidrug resistant Staphylococcus aureus

In the present study, antibacterial activity of aqueous and organic extracts of Psidium guajava leaves was evaluated against multidrug resistant (MDR) clinical isolates of Staphylococcus aureus strains collected from hospitals in northern (Malabar region) Kerala. The strains which exhibited resistance against all the antibiotics tested was selected for antibacterial assays. Minimum inhibitory concentration (MIC) for methanolic and aqueous extracts was found to be 625 ug/ml and 7.5 mg/ml, respectively. Minimum bactericidal concentration (MBC) recorded for methanolic and aqueous extracts was 1.25 and 12.5 mg/ml, respectively. Methanolic extract at minimum bactericidal concentration inhibited the growth of MDR strain by 80%. Time-kill assay revealed that methanolic extract (4 mg/ml) killed MDR bacteria within 10 hr. Total polypeptide profiling of bacterial cultures by SDS-PAGE indicated a high degree of protein degradative activity of the extract. Finally, a human RBC based haemolytic assay showed absence of haemolysis even at concentrations higher than that of MBC, advocating thereby its safety in therapeutic use.     

Transgenic rice expressing <Emphasis Type="Italic">Allium sativum</Emphasis>leaf agglutinin (ASAL) exhibits high-level resistance against major sap-sucking pests

Background  

Rice (Oryza sativa) productivity is adversely impacted by numerous biotic and abiotic factors. An approximate 52% of the global production of rice is lost annually owing to the damage caused by biotic factors, of which ~21% is attributed to the attack of insect pests. In this paper we report the isolation, cloning and characterization of Allium sativum leaf agglutinin (asal) gene, and its expression in elite indica rice cultivars using Agrobacterium-mediated genetic transformation method. The stable transgenic lines, expressing ASAL, showed explicit resistance against major sap-sucking pests.     

Insecticide treated mosquito nets for malaria control in India-experience from a tribal area on operational feasibility and uptake

The study assessed the operational feasibility and acceptability of insecticide-treated mosquito nets (ITNs) in one Primary Health Centre (PHC) in a falciparum malaria endemic district in the state of Orissa, India, where 74% of the people are tribes and DDT indoor residual spraying had been withdrawn and ITNs introduced by the National Vector Borne Disease Control Programme. To a population of 63,920, 24,442 ITNs were distributed free of charge through 101 treatment centers during July-August 2002. Interview of 1,130, 1,012 and 126 respondents showed that the net use rates were 80%, 74% and 55% in the cold, rainy and summer seasons, respectively. Since using ITNs, 74.5-76.6% of the respondents observed reduction of mosquito bites and 7.2-32.1% reduction of malaria incidence; 37% expressed willingness to buy ITNs if the cost was lower and they were affordable. Up to ten months post-treatment, almost 100% mortality of vector mosquitoes was recorded on unwashed and washed nets (once or twice). Health workers re-treated the nets at the treatment centers eight months after distribution on a cost-recovery basis. The coverage reported by the PHC was only 4.2%, mainly because of unwillingness of the people to pay for re-treatment and to go to the treatment centers from their villages. When the re-treatment was continued at the villages involving personnel from several departments, the coverage improved to about 90%.Interview of 126 respondents showed that among those who got their nets re-treated, 81.4% paid cash for the re-treatment and the remainder were reluctant to pay. Majority of those who paid said that they did so due to the fear that if they did not do so they would lose benefits from other government welfare schemes. The 2nd re-treatment was therefore carried out free of charge nine months after the 1st re-treatment and thus achieved coverage of 70.4%. The study showed community acceptance to use ITNs as they perceived the benefit. Distribution and re-treatment of nets was thus possible through the PHC system, if done free of charge and when personnel from different departments, especially those at village level, were involved.     

Unpacking the species conundrum: philosophy,practice and a way forward

The history of ecology and evolutionary biology is rife with attempts to define and delimit species. However, there has been confusion between concepts and criteria, which has led to discussion, debate, and conflict, eventually leading to lack of consistency in delimitation. Here, we provide a broad review of species concepts, a clarification of category versus concept, an account of the general lineage concept (GLC), and finally a way forward for species discovery and delimitation. Historically, species were considered as varieties bound together by reproduction. After over 200 years of uncertainty, Mayr attempted to bring coherence to the definition of species through the biological species concept (BSC). This has, however, received much criticism, and the last half century has spawned at least 20 other concepts. A central philosophical problem is that concepts treat species as ‘individuals’ while the criteria for categorization treats them as ‘classes’. While not getting away from this problem entirely, the GLC attempts to provide a framework where lineage divergence is influenced by a number of different factors (and correlated to different traits) which relate to the different species concepts. We also introduce an ‘inclusive’ probabilistic approach for understanding and delimiting species. Finally, we provide a Wallacean (geography related) approach to the Linnaean problem of identifying and delimiting species, particularly for cases of allopatric divergence, and map this to the GLC. Going one step further, we take a morphometric terrain approach to visualizing and understanding differences between lineages. In summary, we argue that while generalized frameworks may work well for concepts of what species are, plurality and ‘inclusive’ probabilistic approaches may work best for delimitation.     

Molecular dynamics simulations of DNA and a protein-DNA complex including solvent

The results of a recent nanosecond (ns) molecular dynamics (MD) simulation of the d(CGCGAATTCGCG) double helix in water and a 100 ps MD study of the repressor-operator complex are described. The DNA simulations are analyzed in terms of the structural dynamics, fluctuations in the groove width and bending of the helical axis. The results indicate that the ns dynamical trajectory progresses through a series of three substates of B form DNA, with lifetimes of the order of hundreds of picoseconds (ps). An incipient dynamical equilibrium is evident. A comparison of the calculated axis bending with that observed in corresponding crystal structure data is presented. Simulation of the DNA in complex with the protein and that of the free DNA in solution, starting from the crystal conformation, reveal the dynamical changes that occur on complex formation.     

Weight in infancy and prevalence of coronary heart disease in adult life.

OBJECTIVE--To determine whether low birth weight and low weight at 1 year are followed by an increased prevalence of coronary heart disease in adult life. DESIGN--A follow up study of men born during 1920-30 whose birth weights and weights at 1 year were recorded. SETTING--Hertfordshire, England. SUBJECTS--290 men born and still living in East Hertfordshire. MAIN OUTCOME MEASURE--The prevalence of coronary heart disease, defined by the Rose/WHO chest pain questionnaire, standard electrocardiographic criteria, or history of coronary artery angioplasty or graft surgery. RESULTS--42 (14%) men had coronary heart disease. Their mean birth weight, 7.9 lb (3600 g), was the same as that of the other men. Their mean weight at 1 year, 21.8 lb (9.9 kg), was 1 lb (454 g) lower (95% confidence interval 0.1 to 1.8, P = 0.02). Percentages of men with coronary heart disease fell from 27% in those who weighed 18 lb (8.2 kg) or less at 1 year to 9% in those who weighed more than 26 lb (11.8 kg) (P value for trend = 0.03). This trend occurred in both smokers and non-smokers and within each social class. CONCLUSION--These findings add to the evidence that coronary heart disease is "programmed" during early growth.