Drynaria quercifolia suppresses paracetamol­induced hepatotoxicity in mice by inducing Nrf-2.

Paracetamol is a popular and safe drug preferred by victims of pain or pyrexia; however, its overdose or abuse is a growing concern worldwide. Here the hepatoprotective effect of an ethnomedicinal plant Drynaria quercifolia against paracetamol­induced toxicity in murine model is demonstrated. This fern, native to tropical countries including the Northeast India, is used by local tribes to treat inflammatory conditions. Paracetamol 500 mg/kg body weight was orally administered on alternate days for a period of 21days to mimic a chronic overdose. Drynaria quercifolia acetone extract (DQA) treatment interspaced with paracetamol significantly decreased serum biomarkers of hepatotoxicity (ALT, AST and ALP) renal toxicity (urea, creatinine), lipid peroxidation level, histological damage in liver and kidney. The protein and mRNA expressions of the transcription factor, Nrf2, and its target antioxidant genes (SOD1, CAT and GST) as well as activities of these antioxidant enzymes were downregulated by paracetamol administration but significantly recovered following the DQA treatment (Tab. 3, Fig. 5, Ref. 31). Keywords: acetaminophen/paracetamol, Drynaria quercifolia, renal toxicity, hepatotoxicity, Nrf-2.

Imaging stress and magnetism at high pressures using a nanoscale quantum sensor.

Pressure alters the physical, chemical, and electronic properties of matter. The diamond anvil cell enables tabletop experiments to investigate a diverse landscape of high-pressure phenomena. Here, we introduce and use a nanoscale sensing platform that integrates nitrogen-vacancy (NV) color centers directly into the culet of diamond anvils. We demonstrate the versatility of this platform by performing diffraction-limited imaging of both stress fields and magnetism as a function of pressure and temperature. We quantify all normal and shear stress components and demonstrate vector magnetic field imaging, enabling measurement of the pressure-driven [Formula: see text] phase transition in iron and the complex pressure-temperature phase diagram of gadolinium. A complementary NV-sensing modality using noise spectroscopy enables the characterization of phase transitions even in the absence of static magnetic signatures.

Ascorbic acid formulation for survivability and diazotrophic efficacy of Azotobacter chroococcum Avi2 (MCC 3432) under hydrogen peroxide stress and its role in plant-growth promotion in rice (Oryza sativa L.).

Oxidative stress generates reactive oxygen species which causes cell damage of living organisms and are normally detoxified by antioxidants. Indirect reports signify the damages caused by reactive oxygen species and neutralized by antioxidant, but the direct evidence to confirm this hypothesis is still unclear. To validate our hypothesis, an attempt was made in a diazotrophic bacterium (Azotobacter chroococcum Avi2) as a biological system, and hydrogen peroxide (H2O2) and ascorbic acid were used as oxidative stress and antioxidant supplement, respectively. Additionally, rice plant-growth attributes by Avi2 was also assessed under H2O2 and ascorbic acid. Results indicated that higher concentration of H2O2 (2.5 mM-4.5 mM) showed the complete mortality of Avi2, whereas one ppm ascorbic acid neutralized the effect of H2O2. Turbidity, colony forming unit, DNA quantity, nifH gene abundance, indole acetic acid and ammonia productions were significantly (p < 0.5) increased by 11.93%, 17.29%, 19.80%, 74.77%, 71.89%, and 42.53%, respectively in Avi2-treated with 1.5 mM H2O2 plus ascorbic acid compared to 1.5 mM H2O2 alone. Superoxide dismutase was significantly (p < 0.5) increased by 60.85%, whereas catalase and ascorbate peroxidase activities were significantly (p < 0.05) decreased by 64.28% and 68.88% in Avi2-treated with 1.5 mM H2O2 plus ascorbic acid compared to 1.5 mM H2O2 alone. Germination percentage of three rice cultivars (FR13a, Naveen and Sahbhagi dhan) were significantly (p < 0.5) increased by 20%, 13.33%, and 4%, respectively in Avi2-treated with 0.6 mM H2O2 plus ascorbic acid compared with uninoculated control. Overall, this study indicated that ascorbic acid formulation neutralizes the H2O2-oxidative stress and enhances the survivability and plant growth-promoting efficacy of A. chroococcum Avi2 and therefore, it may be used as an effective formulation of bio-inoculants in rice under oxidative stress.

A phase III study comparing SB3 (a proposed trastuzumab biosimilar) and trastuzumab reference product in HER2-positive early breast cancer treated with neoadjuvant-adjuvant treatment: Final safety, immunogenicity and survival results.

BACKGROUND: The equivalent efficacy between SB3, a proposed trastuzumab biosimilar, and the trastuzumab reference product (TRZ) in terms of the breast pathologic complete response rate after neoadjuvant therapy in patients with early or locally advanced human epidermal growth factor receptor 2-positive breast cancer was demonstrated in the previous report. Here, we report the final safety, immunogenicity and survival results after neoadjuvant-adjuvant treatment. PATIENTS AND METHODS: Patients were randomised 1:1 to receive neoadjuvant SB3 or TRZ for 8 cycles concurrently with chemotherapy (4 cycles of docetaxel followed by 4 cycles of 5-fluorouracil/epirubicin/cyclophosphamide). Patients then underwent surgery, followed by 10 cycles of adjuvant SB3 or TRZ as randomised. End-points included safety, immunogenicity, event-free survival (EFS) and overall survival through the adjuvant period. RESULTS: Of 875 patients randomised, 764 (SB3, n = 380; TRZ, n = 384) completed the study. The median follow-up duration was 437 days in the SB3 group and 438 days in the TRZ group. The incidence of treatment-emergent adverse events was comparable between groups (SB3, 97.5%; TRZ, 96.1%) during the overall study period. Up to the end of study, the overall incidence of antidrug antibody was low in both treatment groups (3 patients each). EFS was comparable between groups with a hazard ratio (SB3/TRZ) of 0.94 (95% confidence interval, 0.59-1.51) and EFS rates at 12 months of 93.7% for SB3 and 93.4% for TRZ. CONCLUSIONS: Final safety, immunogenicity and survival results of this study further support the biosimilarity established between SB3 and TRZ. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02149524); EudraCT (2013-004172-35).

Improved intervention of atherosclerosis and cardiac hypertrophy through biodegradable polymer-encapsulated delivery of glycosphingolipid inhibitor.

D-Threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP), a glycosphingolipid synthesis inhibitor, holds promise for the treatment of atherosclerosis and cardiac hypertrophy but rapid in vivo clearance has severely hindered translation to the clinic. To overcome this impediment, we used a materials-based delivery strategy wherein D-PDMP was encapsulated within a biodegradable polymer composed of poly ethylene glycol (PEG) and sebacic acid (SA). PEG-SA was formulated into nanoparticles that were doped with (125)I-labeled PEG to allow in vivo bio-distribution and release kinetics of D-PDMP to be determined by using γ-scintigraphy and subsequently, by mass spectrometry. Polymer-encapsulation increased the residence time of D-PDMP in the body of a treated mouse from less than one hour to at least four hours (and up to 48 h or longer). This substantially increased in vivo longevity provided by polymer encapsulation resulted in an order of magnitude gain in efficacy for interfering with atherosclerosis and cardiac hypertrophy in apoE-/- mice fed a high fat and high cholesterol (HFHC) diet. These results establish that D-PDMP encapsulated in a biodegradable polymer provides a superior mode of delivery compared to unconjugated D-PDMP by way of increased gastrointestinal absorption and increased residence time thus providing this otherwise rapidly cleared compound with therapeutic relevance in interfering with atherosclerosis, cardiac hypertrophy, and probably other diseases associated with the deleterious effects of abnormally high glycosphingolipid biosynthesis or deficient catabolism.

Role of phosphate fertilizers in heavy metal uptake and detoxification of toxic metals.

As a nonrenewable resource, phosphorus (P) is the second most important macronutrient for plant growth and nutrition. Demand of phosphorus application in the agricultural production is increasing fast throughout the globe. The bioavailability of phosphorus is distinctively low due to its slow diffusion and high fixation in soils which make phosphorus a key limiting factor for crop production. Applications of phosphorus-based fertilizers improve the soil fertility and agriculture yield but at the same time concerns over a number of factors that lead to environmental damage need to be addressed properly. Phosphate rock mining leads to reallocation and exposure of several heavy metals and radionuclides in crop fields and water bodies throughout the world. Proper management of phosphorus along with its fertilizers is required that may help the maximum utilization by plants and minimum run-off and wastage. Phosphorus solubilizing bacteria along with the root rhizosphere of plant integrated with root morphological and physiological adaptive strategies need to be explored further for utilization of this extremely valuable nonrenewable resource judiciously. The main objective of this review is to assess the role of phosphorus in fertilizers, their uptake along with other elements and signaling during P starvation.

Nanostructure and strain in InGaN/GaN superlattices grown in GaN nanowires.

The structural properties and the strain state of InGaN/GaN superlattices embedded in GaN nanowires were analyzed as a function of superlattice growth temperature, using complementary transmission electron microscopy techniques supplemented by optical analysis using photoluminescence and spatially resolved microphotoluminescence spectroscopy. A truncated pyramidal shape was observed for the 4 nm thick InGaN inclusions, where their (0001¯) central facet was delimited by six-fold {101¯l} facets towards the m-plane sidewalls of the nanowires. The defect content of the nanowires comprised multiple basal stacking faults localized at the GaN base/superlattice interface, causing the formation of zinc-blende cubic regions, and often single stacking faults at the GaN/InGaN bilayer interfaces. No misfit dislocations or cracks were detected in the heterostructure, implying a fully strained configuration. Geometrical phase analysis showed a rather uniform radial distribution of elastic strain in the (0001¯) facet of the InGaN inclusions. Depending on the superlattice growth temperature, the elastic strain energy is partitioned among the successive InGaN/GaN layers in the case of low-temperature growth, while at higher superlattice growth temperature the in-plane tensile misfit strain of the GaN barriers is accommodated through restrained diffusion of indium from the preceding InGaN layers. The corresponding In contents of the central facet were estimated at 0.42 and 0.25, respectively. However, in the latter case, successful reproduction of the experimental electron microscopy images by image simulations was only feasible, allowing for a much higher occupancy of indium adatoms at lattice sites of the semipolar facets, compared to the invariable 25% assigned to the polar facet. Thus, a high complexity in indium incorporation and strain allocation between the different crystallographic facets of the InGaN inclusions is anticipated and supported by the results of photoluminescence and spatially resolved microphotoluminescence spectroscopy.

Metaphase arrest and delay in cell cycle kinetics of root apical meristems and mouse bone marrow cells treated with leaf aqueous extract of Clerodendrum viscosum Vent.

OBJECTIVES: To study cell cycle delay and metaphase arresting activity of leaf aqueous extract of Clerodendrum viscosum Vent. (LAECV) in root apical meristems and mouse bone marrow cells. MATERIALS AND METHODS: Cell cycle delay and metaphase arresting activities of LAECV were analysed, in root apical meristems of onion and wheat, and in mouse bone marrow cells, by scoring mitotic index, metaphase frequency and transition of cells from metaphase to anaphase. Colchicine was used as the standard metaphase arresting drug. Phytochemicals present in LAECV were detected and their phytotoxic activity was evaluated by analysing green-gram (Vigna radiata) seedling's root growth retardation and branch root swelling phenomenon. RESULTS: LAECV treatment resulted in dose-dependent root growth retardation of green-gram seedling root length (P < 0.01) and half maximal growth inhibitory concentration (IC(50) ) of LAECV was 0.87 mg/ml at 144 h. In onion and wheat root meristem cells the mitotic index decreased, metaphase frequency increased and transition from metaphase to anaphase reduced. Experimentation with mouse bone marrow cells indicated that LAECV induced metaphase arrest (164.3% increase in arrested metaphases per 300 mg/kg body weight, over 2.5 h). Phytochemicals like carbohydrates, glycosides, saponins, terpenoids, triterpenoids, tannins and trace amounts of alkaloids were detected in LAECV. CONCLUSION: It may be said that LAECV contains mitostatic and metaphase arresting components that are able to induce significant metaphase arrest in root apical meristems and also in mouse bone marrow cells.

Bioactive constituents of Homalomena aromatica essential oil and its antifungal activity against dermatophytes and yeasts.

Homalomena aromatica rhizomes are rich source of essential oils, which have been attributed for various medicinal uses. In the present investigation, essential oil from H. aromatica rhizomes was isolated and subjected to gas chromatography-mass spectrum (GC-MS) analysis. Fifty-five chemical constituents were reported from H. aromatica rhizomes of which T-muurolol (5.32%), viridiflorol (3.69%), α-selinene (2.19%), M-cymene (2.19%) and γ-Muurolene (1.81%) were identified and reported for the first time. Other major components were identified as linalool (62.5%), terpene-4-ol (7.08%), δ-cadinene (5.57%), α-cadinol (3.71%) and spatulenol (1.81%). H. aromatica rhizome essential oil showed high antimicrobial activity against Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum fulvum, Microsporum gypseum, Trichosporon beigelii and Candida albicans.

Application of EPR spectroscopy to identify irradiated Indian medicinal plant products.

UNLABELLED: A study of gamma-irradiated Indian medicinal plant products was carried out using electron paramagnetic resonance (EPR) spectroscopy. Improved approaches like high-power measurement, microwave saturation, and thermal behavior of the radicals were explored for detection of irradiation. Aswagandha (Withania somnifera), vairi (Salacia reticulata), amla (Emblica officinalis), haldi (Curcumin longa), and guduchi (Tinospora cordifolia) exhibited a weak singlet at g = 2.005 before irradiation. Aswagandha, immediately after radiation treatment, revealed a complex EPR spectrum characterized by EPR spectrum simulation technique as superposition of 3 paramagnetic centers. One group of signal with organic origin was carbohydrate and cellulose radical and the other was isotropic signal of inorganic origin (g⟂ =2.0044 and g|| = 1.9980). However, other products did not exhibit any radiation-specific signal after irradiation. Power saturation and thermal behavior techniques were not suitable for these products. However, amongst all the 3 approaches, high-power measurement of EPR spectra emerged as a suitable technique in identification of the irradiated aswagandha. PRACTICAL APPLICATION: Gamma-irradiation confirms hygienic quality and improves shelf life of food and other products. However, there is a lack of international consensus over considering this as a general application and different regulations are being enforced. EPR is one of the most promising techniques to identify irradiated foodstuffs for regulatory requirements but it has many limitations. Improved approaches based on the EPR technique explained in this study may be useful to identify irradiated products and become beneficial to food regulators and food irradiation enterprises to enhance confidence in irradiation technology.

The efficacy of dandelion root extract in inducing apoptosis in drug-resistant human melanoma cells.

Notoriously chemoresistant melanoma has become the most prevalent form of cancer for the 25-29 North American age demographic. Standard treatment after early detection involves surgical excision (recurrence is possible), and metastatic melanoma is refractory to immuno-, radio-, and most harmful chemotherapies. Various natural compounds have shown efficacy in killing different cancers, albeit not always specifically. In this study, we show that dandelion root extract (DRE) specifically and effectively induces apoptosis in human melanoma cells without inducing toxicity in noncancerous cells. Characteristic apoptotic morphology of nuclear condensation and phosphatidylserine flipping to the outer leaflet of the plasma membrane of A375 human melanoma cells was observed within 48 hours. DRE-induced apoptosis activates caspase-8 in A375 cells early on, demonstrating employment of an extrinsic apoptotic pathway to kill A375 cells. Reactive Oxygen Species (ROS) generated from DRE-treated isolated mitochondria indicates that natural compounds in DRE can also directly target mitochondria. Interestingly, the relatively resistant G361 human melanoma cell line responded to DRE when combined with the metabolism interfering antitype II diabetic drug metformin. Therefore, treatment with this common, yet potent extract of natural compounds has proven novel in specifically inducing apoptosis in chemoresistant melanoma, without toxicity to healthy cells.

Selective induction of apoptosis through activation of caspase-8 in human leukemia cells (Jurkat) by dandelion root extract.

AIM OF STUDY: Dandelion extracts have been used in traditional Native American Medicine and Traditional Chinese Medicine (TCM) for treatment of leukemia and breast cancer; however, the mechanism of action remains unknown. Today, DRE is mainly marketed for management of gastrointestinal and liver disorders. The current study aims to determine the anti-cancer activity of dandelion root extract (DRE) against human leukemia, and to evaluate the specificity and mechanism of DRE-induced apoptosis. MATERIALS AND METHODS: The effect of DRE on cell viability was evaluated using the colorimetric-based WST-1 assay. Apoptotic cell death was monitored by nuclear condensation and confirmed by exposure of phosphatidylserine to outer leaflet of plasma membrane. Activation of caspases was detected using a fluorogenic substrate specific to either caspase-8 or -3. Loss of mitochondrial membrane potential was observed by microscopy using JC-1 dye. The apoptotic effect of DRE was also evaluated on a dominant-negative FADD (Fas-associated death domain) cell line and non-cancerous peripheral blood mononuclear cells (PBMCs). RESULTS: Aqueous DRE effectively induces apoptosis in human leukemia cell lines in a dose and time dependent manner. Very early activation of caspase-8 and the subsequent activation of caspase-3 indicate that DRE may be inducing extrinsic or receptor-mediated apoptosis. Caspase inhibition rendered this extract ineffective, thus DRE-induced apoptosis is caspase-dependent. Moreover, the dominant-negative FADD cells that are unable to form a complete DISC (death-inducing signaling complex) were resistant to DRE treatment, which further confirms our hypothesis that DRE induces receptor-mediated apoptosis. Interestingly, non-cancerous peripheral blood mononuclear cells (PBMCs) exposed to aqueous DRE under the same treatment conditions as leukemia cells were not significantly affected. CONCLUSION: Our results suggest that aqueous DRE contains components that act to induce apoptosis selectively in cultured leukemia cells, emphasizing the importance of this traditional medicine and thus presents a potential novel non-toxic alternative to conventional leukemia therapy.

A novel Gymnema sylvestre extract stimulates insulin secretion from human islets in vivo and in vitro.

Many plant-based products have been suggested as potential antidiabetic agents, but few have been shown to be effective in treating the symptoms of Type 2 diabetes mellitus (T2DM) in human studies, and little is known of their mechanisms of action. Extracts of Gymnema sylvestre (GS) have been used for the treatment of T2DM in India for centuries. The effects of a novel high molecular weight GS extract, Om Santal Adivasi, (OSA(R)) on plasma insulin, C-peptide and glucose in a small cohort of patients with T2DM are reported here. Oral administration of OSA(R) (1 g/day, 60 days) induced significant increases in circulating insulin and C-peptide, which were associated with significant reductions in fasting and post-prandial blood glucose. In vitro measurements using isolated human islets of Langerhans demonstrated direct stimulatory effects of OSA(R) on insulin secretion from human ß-cells, consistent with an in vivo mode of action through enhancing insulin secretion. These in vivo and in vitro observations suggest that OSA(R) may provide a potential alternative therapy for the hyperglycemia associated with T2DM.

Aerobiological investigation and in vitro studies of pollen grains from 2 dominant avenue trees in Kolkata, India.

BACKGROUND: Peltophorum pterocarpum and Delonix regia are dominant avenue trees in the city of Kolkata in India. They are well adapted to the humid tropical climate and also grow commonly in different parts of the country. Their pollen grains are reported to be airborne. OBJECTIVE: The aim of this study was to conduct an aerobiological survey in Kolkata to determine the concentration and seasonal periodicity of pollen grains from P pterocarpum and D regia and to analyze the meteorological factors responsible for their levels in the atmosphere. In addition, we analyzed the prevalence of sensitization due to these grains among patients with seasonal respiratory allergy. METHODS: An aerobiological survey was conducted with a volumetric Burkard sampler from 2004 to 2006. Correlations between meteorological parameters and pollen grain concentrations were assessed by Spearman correlation test. The protein profile of the pollen extracts was studied by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Finally, the allergenic potential of the pollen extracts was evaluated in patients with respiratory allergy by skin prick test, immunoglobulin (Ig) E enzyme-linked immunosorbent assay, and IgE immunoblotting. RESULTS: P pterocarpum and D regia pollen grains occur from March to June and April to July, respectively. The pollen concentrations showed statistically significant positive correlations with maximum temperature and wind speed. Positive reactions to P pterocarpum and D regia were observed in 26% and 22% of the patients, respectively. Many protein bands were detected in the pollen extracts over a wide molecular weight range. A total of 5 (P pterocarpum pollen) and 8 (D regia pollen) protein fractions were detected by IgE immunoblotting. CONCLUSION: P pterocarpum and D regia pollen grains are dominant in the atmosphere of south Kolkata and they are influenced by temperature. The pollen grains release proteins that may be responsible for immediate hypersensitivity reactions in sensitive patients.

Phoenix sylvestris Roxb pollen allergy: a 2-year randomized controlled trial and follow-up study of immunotherapy in patients with seasonal allergy in an agricultural area of West Bengal, India.

BACKGROUND: Although the efficacy of allergen immunotherapy has been demonstrated in seasonal pollen allergy, there is no report of a double-blind placebo-controlled trial with standardized pollen extract in seasonal respiratory allergy from India. In the agricultural area of eastern India, Phoenix sylvestris Roxb or date sugar palm is grown or cultivated and seasonal allergic rhinitis is common during the pollen season. OBJECTIVE: The objective of the present study was to observe the clinical and immunological changes during a 2-year double-blind placebo-controlled trial of immunotherapy with standardized P sylvestris pollen extract in respiratory patients sensitive to pollen from this wild date palm. Thirty-five subjects with typical seasonal allergic rhinitis with or without bronchial asthma were selected. A symptom-medication score (based on a questionnaire and diary) was correlated with pollen counts as recorded in a Burkard sampler. Eighteen subjects were randomized to a specific immunotherapy (SIT) group receiving regular injections containing standardized allergen extract and 17 to a placebo control group. Changes in the level of specific immunoglobulin (Ig) E, IgG1, and IgG4 were recorded at 3-month intervals. Measurement of wheal diameter, total IgE level and forced expiratory volume in 1 second (FEV1) were performed before starting and a month after finishing therapy. RESULTS: The SIT group showed decreases of 33.5% and 57% from the baseline symptom-medication scores during the first and second treatment season, respectively. This group showed significant decreases in skin-reactivity to P sylvestris pollen extract and in specific IgE levels, and significant increases in FEV,, specific IgGI (1.95-3.2 times higher) and IgG4 (21.24-30.83 times higher). There were no significant changes in total IgE levels. The control group showed no significant changes for any parameter except the development of new sensitization in 2 cases (to Saccharum officinarum pollen grain and Alternaria species spores). The rate of local adverse reactions was 0.024%. CONCLUSION: After a 2-year study, allergen immunotherapy with standardized P sylvestris pollen extract was found to be effective in seasonal respiratory allergic subjects susceptible to P sylvestris pollen with a narrow range of sensitization.

Aerobiological and immunochemical studies on Carica papaya L. pollen: an aeroallergen from India.

BACKGROUND: Carica papaya L. is a fruit yielding tree, wildly grown or cultivated in the tropics and subtropics. Its pollen grain has been reported to be airborne and cause immunoglobulin E (IgE)-mediated hypersensitivity. OBJECTIVE: To conduct long-term aerobiological study on Carica pollen, along with aeroallergenic particles originating from it and to identify vis-a-vis characterize an important IgE-reactive component present in this pollen. METHODS: The seasonal and diurnal periodicities of airborne C. papaya pollen were recorded in a 5-year survey using a Burkard volumetric sampler. The allergenic potential was studied by skin prick tests, IgE-enzyme-linked immunosorbent assay (ELISA) and also by aeroallergen immunoblotting. The total pollen extract was fractionated by Sephacryl S-200 column, and out of the eluted five fractions, the maximum IgE-reactive fraction (as found in ELISA inhibition) was resolved into five major subfractions in reverse-phase high-performance liquid chromatography (RP-HPLC). The subfraction with optimum IgE reactivity was studied by activity gel, native and nonreducing sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). The homogeneity of the isolated protein fraction was checked by crossed immunoelectrophoresis with rabbit antisera and IgE reactivity was confirmed by ELISA inhibition and immunoblotting using individual patient sera. RESULTS: The Carica pollen occurred in the air round the year with peaks during January and September-October. Among a patient population of 1000, skin-test results showed 27.8% +1 level and 5.6% +2/+3 level reactions. In aeroallergen immunoblotting of exposed Burkard tape segments, the detected allergen spots showed a significant correlation with airborne pollen count recorded. The pollen extract elicited loss of IgE reactivity when treated with reducing agent-like beta-mercaptoethanol and heat, but showed six IgE-reactive components in nonreducing IgE-immunoblot. The fraction 1 eluted from Sephacryl S-200 column showed highest IgE reactivity and resolved into five major components in RP-HPLC. Out of these, the fraction showing optimum IgE reactivity in IgE-ELISA inhibition and immunoblotting with patient antisera, elicited esterase activity and found to be a homogenous protein of 100 kDa. CONCLUSION: Carica papaya tree contributes significantly to the aeropollen and aeroallergen load of the suburban outskirts of Calcutta metropolis, India. The pollen extract contains an important IgE-reactive protein component of 100 kDa molecular weight with esterase activity.

Evaluation of markers of endothelial damage in cases of young myocardial infarction.

The pathogenesis of arterial thrombotic disease involves multiple genetic and environmental factors related to atherosclerosis and thrombosis. The endothelium is a monolayer of polygonal cells that extend continuously over the luminal surface of the entire vasculature. Injury to the endothelium leads to dysfunction. The causes of injury include lipids, immune complexes, microorganisms, smoking, hypertension, aging, diabetes mellitus and trauma. Studies have been done to evaluate the role of different adhesion molecules on the endothelial membrane in the pathogenesis of atherosclerosis. These molecules are intercellular adhesion molecule type-1 (ICAM-1), vascular cell adhesion molecule type-1 (VCAM-1), platelet/endothelial cell adhesion molecule-1 (PECAM-1), soluble P-selectin (sP-selectin) and soluble E-selectin (sE-selectin). One-hundred and twenty patients of myocardial infarction (age below 40 years) were recruited from the out-patients department of Department of Cardiology, KEM Hospital, Mumbai. All the patients were recruited 8-10 weeks after stabilization after MI. We estimated the levels of sP-selectin, sE-selectin, sPECAM-1 and serum homocysteine. Healthy age and sex-matched controls and family controls were also recruited in the present study. The levels of sP-selectin, sE-selectin and sPECAM-1 did not differ significantly in cases as compared to controls (p>0.05). Hyperhomocysteinemia was significantly associated with MI in comparison with controls (p<0.001) with an odds ratio of 6.26 (95% confidence limits 3.11-12.76). Folic acid was able to correct hyperhomocysteinemia in a large majority of the cases. Although the levels of sP-selectin, sE-selectin and sPECAM-1 decreased after folic acid therapy, it was only sE-selectin which was significantly reduced (p<0.05). Thus, folic acid had a dual effect in that it reduced hyperhomocysteinemia and sE-selectin which showed a significant reduction on folate supplementation for 15 days.

Cognitive and other behavioral effects of EGb 761 in animal models.

Extensive pre-clinical and clinical studies conducted over more than three decades have established that EGb 761 (definition see editorial) represents a polyvalent therapeutic principle that is useful in the therapy of mildly to moderately severe dementia and other cognitive disorders. Besides cognition, other emotional and affective aspects of brain function also seem to benefit from EGb 761 treatment. Extensive behavioural studies in experimental animals are generally in line with clinical data since cognition improvement, stress protection, and antidepressive effects have been identified with this extract in proper animal models. While individual effects in all areas have been reported for adult animals and acute dosing, more pronounced effects are usually seen in aged animals and after subchronic treatment. Specifically, for the cognition improving properties pronounced beneficial effects are mainly present in those situations where cognition was impaired by aging or other noxious stimuli. Since all these conditions are associated with mitochondrial dysfunction, the stabilizing or even protecting effect of EGb 761 on mitochondrial function seems to be a major mechanism associated with many of EGb 761's behavioural effects. Bilobalide is most important in this respect. Moreover, bilobalide and the ginkgolides have recently been shown to affect chloride conductance by interfering with the function of membrane proteins related to receptor-gated chloride channels. These mechanisms are probably associated with behavioural effects requiring acute changes of neuronal activity, but might indirectly also improve mitochondrial function.

Structure-activity studies with Ginkgo biloba extract constituents as receptor-gated chloride channel blockers and modulators.

The constituents of Ginkgo biloba leaf extract, ginkgolides A, B, C and J are known as effective antagonists of platelet-activating factor (PAF). Here, we will demonstrate that these substances are also effective blockers of glycine-activated chloride channels in the hippocampal neurons of rat. As examined in several other voltage- and ligand-operated channels, this ginkgolide action is selective. The blocking action of all tested ginkgolides is use-dependent--they block open glycine-activated channels. The IC (50) values for saturating blocking action of ginkgolides B and C are 0.273 microM and 0.267 microM, respectively, while ginkgolides A and J are less effective--IC (50) values are 1.97 microM and 2.0 microM. Corresponding dose-response relationships are close to single-site binding isotherms. Another constituent of EGb 761, bilobalide, is a weak inhibitor of NMDA receptor-activated current. Its synthetic analogue, NV-31, demonstrates a weak facilitatory action on Gly-activated conductance. Novel findings have indicated the possibility that the unique modulating activity profiles of the EGb 761 (definition see editorial) constituents examined are due to their effects on the anion homeostasis of central neurons.