Immune response to n-terminal and c-terminal deletion mutants of Aspergillus fumigatus major allergen ASP F 3

The ubiquitous fungus Aspergillus fumigatus causes allergic rhinitis, asthma, sinusitis and allergic bronchopulmonary aspergillosis. A number of major allergens from A. fumigatus are purified, but their structure-function role in the pathogenesis of disease is not known. Such information is essential for devising alternative therapy of fungal allergic diseases. In the present study, N-terminal and C-terminal deletion mutants ofAsp f 3 were constructed and their immunopathological responses studied in a mice model of allergy. Three mutants viz,Asp f 3 (aa 33–168), (aa 1–142), and (aa 23–142) were made by deleting certain amino acids from epitopic regions of full lengthAsp f 3, a major allergen of A. furnigatus. TheAsp f 3 and three mutated proteins were expressed in pET vector. The C-terminal deletion mutantAsp f 3 (aa 1–142) induced elevated IFN-γ but low levels of IL-4 by spleen cells. This mutant also showed significant downregulation of peripheral blood eosinophils and lung inflammation in immunized mice. The N-terminal deletion mutantAsp f 3 (aa 33–168) also exhibited an immuno-suppressive effect in terms of IgE production and induction of Th2 cytokine. The results indicate thatrAsp f 3 and its deletion mutants induced distinct immune-inflammatory responses in mice on challenge with these proteins. The non-IgE binding deletion mutants ofAsp f 3 (aa 1–142 and aa 33–168) could deviate Th2 immune response with a concomitant reduction in airway inflammation and infiltration of inflammatory cells.     

Antioxidant status and peroxidative stress in mother and newborn —A pilot study

Serum antioxidant status and peroxidative stress was estimated in 30 pregnant women, their newborn infants and 25 non-pregnant women. Serum Ascorbic acid, α-tocopherol, retinol & β-carotene levels were found to be significantly reduced and peroxidative stress was significantly higher in mothers as compared to matched non-pregnant women. Newborn had significantly higher levels of ascorbic acid as compared to their mother but had significantly lower levels of lipid soluble vitamins. The peroxidative stress in newborn was found to be significantly less as compared to their mothers. A positive correlation of ascorbic acid and α-tocopherol levels between mother and newborn reflects that their status in mother does influence the newborn status.     

Application of Sigma Metrics for the Assessment of Quality Assurance in Clinical Biochemistry Laboratory in India: A Pilot Study

Ensuring quality of laboratory services is the need of the hour in the field of health care. Keeping in mind the revolution ushered by six sigma concept in corporate world, health care sector may reap the benefits of the same. Six sigma provides a general methodology to describe performance on sigma scale. We aimed to gauge our laboratory performance by sigma metrics. Internal quality control (QC) data was analyzed retrospectively over a period of 6 months from July 2009 to December 2009. Laboratory mean, standard deviation and coefficient of variation were calculated for all the parameters. Sigma was calculated for both the levels of internal QC. Satisfactory sigma values (>6) were elicited for creatinine, triglycerides, SGOT, CPK-Total and Amylase. Blood urea performed poorly on the sigma scale with sigma <3. The findings of our exercise emphasize the need for detailed evaluation and adoption of ameliorative measures in order to effectuate six sigma standards for all the analytical processes.     

Changes in serum copper levels in patients with malignant diseases undergoing radiotherapy

Present study repots changes in serum copper levels (SCL) in various neoplastic diseases undergoing radiotherapy. We estimated SCLs in 140 individuals comprising of 90 previously untreated patients with various malignancies and 50 healthy controls. Patients received radiation in doses of 40–70 Gy in 4–7 weeks. SCLs were again estimated in patients following irradiation. The mean SCL was significantly higher (P<0.001) in cancer patients as compared to healthy controls. It declined significantly (P<0.001) following irradiation. However, it remained significantly higher as compared to healthy controls (P<0.01). Highest fall in SCL was seen in complete clinical responders and least in non-responders to radiation treatment. Serial estimation of SCLs may be useful in the treatment monitoring of the neoplasms undergoing radiation treatment.     

Acid base status in chronic obstructive pulmonary disease patients

348 patients of chronic obstructive pulmonary diseases (COPD) were studied for their acid base profile using ABL-3 blood gas analyser (Radiometer, copenhagan). 185 patients (53.1%) had simple disorders (respiratory acidosis—53%, respiratory alkalosis—25.4%, metabolic acidosis—11.3%, metabolic alkalosis—10.2%). Mixed disorders were present in 131 patients (34.9%) (respiratory acidosis and metabolic acidosis—75.2%, respiratory acidosis and metabolic acidosis—14%, metabolic acidosis and metabolic alkalosis—5.7%, metabolic alkalosis and respiratory alkalosis—4.9%). Hypoxemia without other acid base abnormalities was observed in early patients of GOPD (42 patients—12%). Chronic respiratory acidosis was the most common finding in advanced cases of COPD (98%). An almost equal number of such patients had a mixed disorder of respiratory acidosis with metabolic alkalosis (91%). Salt restriction, prolonged use of steriods and hypokalemia were often related to metabolic alkalosis in such patients.     

Neurochemical and Behavioral Dysfunctions in Pesticide Exposed Farm Workers: A Clinical Outcome

The problem of pesticides is not new and its exposure to human due to indiscriminate use is largely associated with the health related problems including neurotoxicological alterations. High levels of pesticide residues and their metabolites in the dietary constituents, food materials, maternal blood, cord blood, placenta breast milk have been reported and linked to alterations in birth weight, crown heel length, head circumference, mid-arm circumference and ponderal index of the neonates. Epidemiological studies have suggested that exposure of pesticide to human could be a significant risk factor for neurological disorders, including Parkinson’s disease, Alzheimer’s disease and multiple sclerosis. Cholinergic and non-cholinergic dysfunctions in pesticide exposed population, especially in children have also been frequently reported in recent years. Developmental neurotoxicity is another concern in the area where pregnant are more prone towards its exposure and which results in the abnormalities in the fetus. In view of the increasing risk of human health through pesticide exposure, the present review has been focused on the studies pertaining to pesticide induced neurochemical alterations and associated behavioral abnormalities in farm workers which could establish a possible link between the its exposure and associated health hazards.     

Distributed R&D, cross-regional knowledge integration and quality of innovative output

We explore the impact of geographic dispersion of a firm's R&D activities on the quality of its innovative output. Using data on over half a million patents from 1127 firms, we find that having geographically distributed R&D per se does not improve the quality of a firm's innovations. In fact, distributed R&D appears to be negatively associated with average value of innovations. This suggests that potential gains from access to diverse ideas and expertise from different locations are, on average, offset by difficulty in achieving integration of knowledge across multiple locations. To investigate whether the innovating teams that do manage cross-fertilization of ideas from different locations achieve more valuable innovations, we analyze innovations for which there is evidence of such knowledge cross-fertilization along any of the followings dimensions: knowledge sourcing from other locations within the firm, having at least one inventor with cross-regional ties, and having at least one inventor that has recently moved from another region. Analysis along all three dimensions consistently reveals a direct positive effect cross-regional knowledge integration has on innovation quality, as well as a positive interaction effect of cross-regional knowledge integration and distributed R&D for innovation quality. More generally, our findings provide new evidence regarding the importance of cross-unit integrative mechanisms for achieving superior performance in multi-unit firms.     

Association of Cholesteryl Ester Transfer Protein (CETP) Gene -629C/A Polymorphism with Angiographically Proven Atherosclerosis

Association of cholesteryl ester transfer protein (CETP) Gene -629C/A Polymorphism with angiographically proven atherosclerosis CETP gene has been linked to CAD risk via its role in HDL and LDL metabolism. There is no agreement of whether CETP is atherogenic or not. Furthermore, various genotypes of CETP gene have been associated with CETP levels and thus with atherosclerosis risk. Our aim was to study the association of CETP -629C/A gene polymorphism with CETP and HDL levels and their association if any with atherosclerosis. Study population consisted of angiographically documented 50 cases with coronary artery atherosclerosis and 50 controls negative for atherosclerosis of coronary artery. Serum lipid profile was measured on SYNCHRON CX-9 using standard kits. Serum CETP levels were measured by ELISA method. CETP -629C/A gene polymorphism was studied using PCR–RFLP method. There was no significant difference in lipid profile of the two groups. However, serum CETP level was significantly higher (46.44 ± 21.75 ng/ml) in cases than controls (37.10 ± 21.92 ng/ml) with p value =0.035. The frequency of -629A allele was higher (0.85) in cases than that of controls (0.81). Homozygosity of A allele was more in subjects with atherosclerosis of coronary artery. We conclude that CETP is atherogenic and could be used as atherogenic risk predictor in angiographically proven atherosclerosis. Also A allele of -629C/A polymorphism is more prevalent in cases; indicating its effect on expression of CETP gene.     

Lipid peroxidation and antioxidant vitamins in urolithasis

The present, study was conducted to determine the level of malondialdehyde (MDA) as an index of free radial induced lipid peroxidation and antioxidant vitamins-vitamins A, vitamin C and vitamin E in 75 confirmed cases of urolithiasis. Significantly high level of MDA (p<0.001) with significantly low levels of vitamin E (p<0.001) and vitamin A (p<0.001) with no significant decrease in vitamin C (p>0.05) were observed in the plasma of urolithiasis cases as compared to normal controls. In conclusion, it appears that a role of lipid peroxidation and oxidative function exists in the pathogenesis of urolithiasis. But, the exact mechanism how this occurs remains to be elucidated.