Immunoprotective effect of lentinan in combination with miltefosine on Leishmania-infected J-774A.1 macrophages.

Rejuvenation of deteriorated host immune functions is imperative for successful annihilation of Leishmania parasites. The use of immunomodulatory agents may have several advantages as they conquer immunosuppression and, when given in combination, improve current therapeutic regimens. We herein investigated the immunostimulatory potency of a ß-glucan, lentinan either alone or in combination with short dose of standard drug, miltefosine on Leishmania-infected J-774A.1 macrophages. Our study shows that infected macrophages when stimulated with 2.5 µg/mL and above concentrations of lentinan secreted significant amount of host-protective molecules. The in vitro interaction between lentinan and miltefosine showed some synergy (mean sum of fractional inhibitory concentration [mean ∑FIC] 0.87) at IC50 level. Lentinan (2.5 µg/mL) plus low-dose miltefosine (2 µM) displayed heightened level of pro-inflammatory cytokines, IL-12 (13.6-fold) and TNF-α (6.8-fold) along with nitric oxide (7.2-fold higher) when compared with infected control. In combination group, we also observed remarkably (P<.001) suppressed levels of anti-inflammatory cytokines, IL-10 and TGF-ß, than that of untreated macrophages. Additionally, in comparison with infected group, we observed significant induction in phagocytic activity of macrophages in combination with treated group. Collectively, these findings emphasize the immunostimulatory effect of lentinan alone and in combination with low dose of miltefosine against Leishmania donovani.

Phosphate solubilizing and indole-3-acetic acid producing bacteria from the soil of Garhwal Himalaya aimed to improve the growth of rice.

In the present study, soil bacteria from rainfed agriculture field of Garhwal Himalaya, just prior to sowing of summer crop, were isolated and initially tested for solubilization of inorganic phosphate, production of indole acetic acid (IAA) and siderophore. Two bacterial isolates, having efficient P- solubilizing activity in solid medium, were identified using 16S rRNA sequence analysis as Pseudomonas koreensis strainYB1 Arthrobacter nitroguajacolicus strainYB3 and three bacterial isolates, producing high amount of IAA in liquid medium, were identified as Klebsiella oxytoca strainYB2 and two strain of Arthrobacter nitroguajacolicus, strainYB4 and YB5, respectively. In culture medium supplemented with L-Tryptophan, Klebsiella oxytoca produced high amount of IAA (337.44 µg l(-1)). The selected five bacterial strains were further tested for tricalcium phosphate (TCP) solubilizing abilities at three different incubation temperature viz., 4 degrees C, 10 degrees C and 28 degrees C, under in vitro conditions. At 28 degrees C, three bacterial strains Pseudomonas koreensis, Arthrobacter nitroguajacolicus strainYB4 and Klebsiella oxytoca solubilized the phosphate efficiently. At 10 degrees C only two strains, Pseudomonas koreensis and Arthrobacter nitroguajacolicus strainYB4 solubilized phosphate efficiently as compared to other strains. These five bacterial strains were tested for nitrogen, catalase activity, starch and cellulose hydrolysis as well as growth promotion activity on rice, under controlled conditions. All the five bacterial strains efficiently increased the biomass and phosphorus uptake in Swama and Swarna sub1 varieties of rice.

Antifungal activity, SAR and physicochemical correlation of some thiazole-1,3,5-triazine derivatives.

OBJECTIVE: Present research communication was towards the investigation of antifungal minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) activity of some substituted clubbed thiazole-1,3,5-triazines derivatives and effect of physicochemical properties on bioactivity. MATERIAL AND METHODS: MIC and MFC were evaluated against Candida albicans, Candida glabrata, Cryptococcus neoformans and Aspergillus niger using modified microdilution method recommended by CLSI. Cytotoxicity was determinate on the viability of marine shrimp larvaes. SAR and physicochemical correlations were studied by Molinspiration software. RESULTS: The 5 and 9 derivatives showed an excellent antifungal activity with MIC lower than fluconazole and equivalent to amphotericin B specially against C. albicans and C. glabrata. The toxicity of these two derivatives was non-existent for 5 and moderate for 9 at the used concentration. SAR study around prototype molecule suggests that presence of di-hydrophobic fragment on 1,3,5-triazine is necessary for antifungal activity than halogen substituted aromatic amine. CONCLUSION: On the basis of selectivity, potency and non-toxicity, we have obtained two molecules (5 and 9) as prospective leads for further research work on 1,3,5-triazine as antifungal drug.

Effect of cholecalciferol and calcium supplementation on muscle strength and energy metabolism in vitamin D-deficient Asian Indians: a randomized, controlled trial.

CONTEXT: Vitamin D deficiency is prevalent worldwide. Vitamin D supplementation has shown variable effect on skeletal muscle strength in the elderly with hypovitaminosis D. There is a paucity of similar data in young individuals. OBJECTIVE: To study the effect of cholecalciferol and calcium supplementation on muscle strength and energy metabolism in young individuals. SUBJECTS: Forty healthy volunteers (24 M/16 F, mean age (SD) 31.5 ± 5.0 year) with hypovitaminosis D were randomized to either oral cholecalciferol (60,000 IU D3/week for 8 weeks followed by 60,000 IU/month for 4 months) with 1 g of elemental calcium daily or dual placebos for 6 months. MEASUREMENTS: Handgrip and gastro-soleus dynamometry, pinch-grip strength, respiratory pressures, 6-min walk-test and muscle energy metabolism on (31) P magnetic resonance spectroscopy were assessed at baseline and after 6 months. RESULTS: The mean serum 25(OH)D in the supplemented and placebo groups at baseline, two and 6 months were 25.4 ± 9.9, 94.5 ± 53.8 and 56.0 ± 17.0 nm, and 21.1 ± 9.4, 32.8 ± 14.4 and 29.7 ± 15.0 nm, respectively. The supplemented group gained a handgrip strength of 2.4 kg (95% C.I. = 1.2-3.6); gastro-soleus strength of 3.0 Nm (95% C.I. = 0.1-5.9) and walking distance of 15.9 m (95% C.I. = 6.3-25.5) over the placebo group after adjustment for age, gender and respective baseline parameters. Muscle energy parameters were comparable at 6 months. CONCLUSIONS: Six months of cholecalciferol and calcium supplementation results in enhanced skeletal muscle strength and physical performance despite no change in muscle energy parameters. Cholecalciferol supplementation of 60,000 IU per month could not maintain 25(OH)D levels in the sufficient range.

Lipid peroxidation and antioxidants in different stages of cervical cancer: Prognostic significance.

BACKGROUND: Free radical Injury is associated with cancer, but how the extent of oxidative stress correlates with the FIGO (International Federation of Gynecology and Obstetrics) stage in Carcinoma Cervix (Ca Cx), and its significance as a prognostic marker, is not clear and needs an in-depth study. AIM: To correlate the blood levels of Lipid Peroxidation (LPO), Reduced Glutathione (GSH), Superoxide Dismutase (SOD), and Vitamin A and E levels with the clinical stage in Ca Cx. SETTINGS AND DESIGN: This is a Prospective Case Control Study. MATERIALS AND METHODS: LPO, SOD, reduced GSH were estimated by Bio Chemical Assays and Vitamins by High Performance Liquid Chromatography (HPLC). STATISTICAL ANALYSIS: The cases and controls were compared using One Way ANOVA and different stages over different time periods were individually compared by Repeated Measure Analysis of Variance. RESULTS: The results indicated a statistically significant increase of LPO vis-a-vis the FIGO stage of Ca Cx and control, while the antioxidant status as depicted by GSH and SOD decreased. Vitamin A and E levels were significantly lower in cancer cases as compared to the control. CONCLUSION: Increased LPO and reduced antioxidant levels may be taken as associated predictive markers, thus suggesting that Ca Cx cases should get nutritive supplements to contain the blood LPO level and maintain a positive balance of antioxidants for a better outcome in terms of delayed recurrence and better Quality of Life (QOL).

Antifungal activity of the alkaloids from Eschscholzia californica.

The isoquinoline alkaloids hunnemanine and norsanguinarine have been isolated from methanolic extract of the whole plant of Eschscholzia californica. These two alkaloids were checked for their antifungal activity against phytopathogenic fungi Alternaria melongenae, A. brassicola, A. brassicae, Curvularia lunata, C. maculans, Helminthosporium pennisetti, H. oryzae, H. turcicum, Fusarium undum and F. lini. Hunnemanine exhibited 100 % inhibition of spore germination of A. brassicae, H. pennisetti and F. lini at 1000 ppm whereas norsanguinarine exhibited 100 % inhibition of A. brassicicola and C. maculans at this concentration.

Comparative clinical trial of castor oil and diclofenac sodium in patients with osteoarthritis.

A randomized, double-blind, comparative clinical study was conducted to compare the safety and efficacy of castor oil with diclofenac sodium in patients with knee osteoarthritis. Subjects with symptoms of knee osteoarthritis were given a castor oil capsule 0.9 mL (n = 50) thrice daily for 4 weeks or a capsule of diclofenac sodium (n = 50), 50 mg thrice daily for 4 weeks. The subjects completed an overall evaluation of symptom relief at 2 weeks and 4 weeks of completed treatment. The subjects were evaluated by clinical, routine laboratory and radiographic investigations for improvement of disease conditions and also for adverse drug reaction. On completion of 4 weeks treatment it was observed that both drugs were significantly effective in the treatment of knee osteoarthritis (p < 0.001) and adverse drug reactions were high with diclofenac sodium, whereas with castor oil there were no adverse effects reported. The present study indicates that castor oil can be used as an effective therapy in primary knee osteoarthritis.

A new chalcone glycoside from Rhamnus nipalensis.

A new chalcone glycoside, chalcone-2',4-dihydroxy-4'-O-beta-D-glucoside has been isolated from Rhamnus nipalensis together with sitosterol, lupeol, di-O-methyldaidzein, kaempferol-4'-methylether, quercetin, physcion, sitosterol glucoside, emodin and their structures established by spectroscopic data. Isolation of these compounds are the first report from this plant.

Vitamin E: inflammation and atherosclerosis.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the western world with its incidence increasing lately in developing countries. Several lines of evidence support a role for inflammation in atherogenesis. Hence, dietary micronutrients having antiinflammatory properties may have a potential beneficial effect with regard to CVD. Vitamin E is a potent antioxidant with antiinflammatory properties. It comprises eight different isoforms: four tocopherols (T) (alpha, beta, gamma, and delta) and four tocotrienols (T3) (alpha, beta, gamma, and delta). A wealth of data is available for the preventive efficacy of alpha-T. alpha-T supplementation in human subjects and animal models has been shown to be antioxidant and antiinflammatory in terms of decreasing C-reactive protein (CRP) and release of proinflammatory cytokines, the chemokine IL-8 and PAI-1 levels especially at high doses. gamma-T is effective in decreasing reactive nitrogen species and also appears to have antiinflammatory properties; however, there are scanty data examining pure gamma-T preparations. Furthermore, tocotrienols (alpha and gamma) also have implications for prevention of CVD; however, there are conflicting and insufficient data in the literature with regards to their potency. In this chapter, we have gathered recent emerging data on alpha-T specifically and also have given a composite view of gamma-T and tocotrienols especially with regards to their effect on inflammation as it relates to CVD.

Chemotaxonomic variability in Zizyphus mouritiana varieties and its pharmacological properties in relation to human health.

Twenty varieties of ber (Zizyphus mouritiana), namely umaran, katha, bilayati, kaithli, ZG-3, gola, safeda rohtak, takadi, tikari, banarasi karaka, seo, sonaur-2, sonaur-3, ilaichi, mundia murahra, pathan, kakrola gola, seb, golden yellow and chhuhara, were investigated for the presence of phenolic acids in stem bark, leaves and fruits using high performance liquid chromatograph. Results indicated the presence of tannic (retention time (Rt.) 2.76 min), gallic (Rt. 2.86 min), caffeic (Rt. 3.12 min), vanillic (Rt. 3.26 min), ferulic (Rt. 3.42 min), chlorogenic (Rt. 4.16 min) and cinnamic acids (Rt. 4.45 min) in varying amounts in different parts in of these varieties. In fruits of seven varieties, namely, kaithly, sonaur-2, sonaur-3, mundia murahra, pathan, golden yellow and chhuhara, oxalic acid (Rt. 3.00 min) was also detected. Pharmacological properties of phenolic acids of fruits in relation to human health and the possible implications of different phenolic acids in chemotaxonomy of different varieties of ber are discussed.

DOTS at a tertiary care center in northern India: successes, challenges and the next steps in tuberculosis control.

BACKGROUND AND OBJECTIVES: The past decade has seen a rapid expansion of directly observed treatment, short-course (DOTS) centers throughout India, under the guidance of the Revised National Tuberculosis Control Programme (RNTCP). While expansion has been rapid and extensive, few reports exist detailing individual DOTS centers' experiences, their challenges, and their successes. We present a brief report on the status of a DOTS center being run at a large tertiary care center in northern India for almost four years (2001-2005). METHODS: The DOTS center followed RNTCP guidelines for the evaluation and treatment of suspected TB cases. A register carrying detailed information of all patients seen at the DOTS center was kept by the senior clinician. Data from this register were extracted and analyzed for descriptive measures. RESULTS: A total of 1490 patients were evaluated. Of the 768 patients with cough, 27 per cent (211) were found to be sputum positive for acid-fast bacilli (AFB). Among patients who were initiated on anti-tuberculosis medications, cure was achieved in 92 per cent (71 of 77) of new sputum smear positive patients; treatment completion was achieved in 91 per cent (91 of 100) of extrapulmonary TB (EPTB) and 75 per cent (46 of 61) of sputum-negative pulmonary TB patients. Overall treatment success was achieved in 86 per cent (229 of 266). INTERPRETATION AND CONCLUSION: Treatment results were in keeping with the RNTCP guidelines. Tertiary care centers appear to be excellent place for education of medical students and operational research. The latter is much needed, as HIV-TB co-infection, multi-drug resistant TB, and EPTB continue to be major public health threats even in the era of DOTS.

Evaluation of capsaicin ointment at the Korean hand acupressure point K-D2 for prevention of postoperative nausea and vomiting.

The K-D2 point is the Korean hand acupressure point in Koryo Hand Therapy for prevention of postoperative nausea and vomiting. We evaluated the efficacy of capsaicin ointment at the K-D2 point in 186 patients undergoing laparoscopic cholecystectomy in a randomised, prospective, double-blind and placebo-controlled study. Patients were randomised to have either placebo ointment or capsaicin ointment applied to the K-D2 point of both hands 1 h before surgery under standardised anaesthesia. The ointment was removed 8 h later. Postoperative nausea and vomiting was evaluated 6 and 24 h following surgery. The incidence of postoperative nausea and vomiting was lower in the capsaicin group, with an absolute risk reduction (ARR) of 21%, a relative risk reduction (RRR) of 50% and a number-needed-to-treat (NNT) of 5 at 0-6 h (p = 0.001), and an ARR of 11%, a RRR of 85% and a NNT of 9 at 6-24 h (p = 0.003). The need for rescue anti-emetic treatment was also lower at 0-6 h (3 (3%) vs 11 (12%); p = 0.04) and at 6-24 h (5 (5%) vs 0; p = 0.02).

Acupressure for prevention of pre-operative anxiety: a prospective, randomised, placebo controlled study.

Pre-operative anxiety is associated with many unwanted effects such as increased analgesic and anaesthetic requirement, postoperative pain and prolonged hospital stay. In the present study, we investigated the effects of acupressure on pre-operative anxiety and bispectral index (BIS) values. Seventy-six adults, ASA grade I and II, undergoing elective surgery, were randomly assigned to two equal groups. Group 1 (control) received acupressure at an inappropriate site and group 2 (acupressure) received acupressure at extra 1 point. The study was conducted during the pre-operative period and the duration of the study was 40 min (acupressure was applied for 10 min and thereafter patients were observed for another 30 min). Anxiety was recorded on a visual stress scale (VSS) at the start of the study and thereafter at 10 and 40 min. BIS was recorded at 0, 2, 5, 10, 12, 15, 30 and 40 min. The VSS decreased in both groups following pressure application for 10 min: median VSS (interquartile range) were 5 (1) vs. 8 (1) in the acupressure and 7 (0) vs. 8 (1) in the control groups (p < 0.001). Both pre-operative anxiety and BIS decreased significantly during acupressure application at extra 1 point (p < 0.001). Acupressure is effective in decreasing both pre-operative anxiety and BIS; however, these effects are not sustained 30 min following release of acupressure. Further studies are needed to elucidate the duration for which acupressure is effective.

Phenolic acids in neem (Azadirachta indica): a major pre-existing secondary metabolites.

High Performance Liquid Chromatographic (HPLC) analyses of various parts (fresh and dry bark of stem, mature and tender leaves, flower and different parts of fruit, i.e., raw and ripe fruit epicarp, mesocarp and seed) of neem (Azadirachta indica), which occupies an important place in socio-cultural-religious life in Indian communities, indicate that neem is rich in pre-existing secondary metabolites (phenolic acids). Dry bark showed only tannic acid but in fresh bark three phenolic acids were observed, i.e., gallic, tannic, and ferulic acids. In tender leaves only gallic and ferulic acids were detected, but the levels of these phenolic acids in mature leaves were about three times and fifty times greater, respectively. Flowers had only two phenolic acids in which gallic acid was maximum followed by chlorogenic acid. The level of phenolic acid was maximum in seeds followed by epicarp and pulp. In raw and ripe fruit seeds four phenolic acids were detected. Raw fruit seeds were rich in phenolic acids than ripe fruit seeds. Fruit epicarp was relatively richer than seed, seed pulp and flowers of the plants. Neem flowers were also rich in gallic and chlorogenic acids.

Vitamin E, oxidative stress, and inflammation.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Western world. Its incidence has also been increasing lately in developing countries. Several lines of evidence support a role for oxidative stress and inflammation in atherogenesis. Oxidation of lipoproteins is a hallmark in atherosclerosis. Oxidized low-density lipoprotein induces inflammation as it induces adhesion and influx of monocytes and influences cytokine release by monocytes. A number of proinflammatory cytokines such as interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) modulate monocyte adhesion to endothelium. C-reactive protein (CRP), a prototypic marker of inflammation, is a risk marker for CVD and it could contribute to atherosclerosis. Hence, dietary micronutrients having anti-inflammatory and antioxidant properties may have a potential beneficial effect with regard to cardiovascular disease. Vitamin E is a potent antioxidant with anti-inflammatory properties. Several lines of evidence suggest that among different forms of vitamin E, alpha-tocopherol (AT) has potential beneficial effects with regard to cardiovascular disease. AT supplementation in human subjects and animal models has been shown to decrease lipid peroxidation, superoxide (O2-) production by impairing the assembly of nicotinamide adenine dinucleotide phosphate (reduced form) oxidase as well as by decreasing the expression of scavenger receptors (SR-A and CD36), particularly important in the formation of foam cells. AT therapy, especially at high doses, has been shown to decrease the release of proinflammatory cytokines, the chemokine IL-8 and plasminogen activator inhibitor-1 (PAI-1) levels as well as decrease adhesion of monocytes to endothelium. In addition, AT has been shown to decrease CRP levels, in patients with CVD and in those with risk factors for CVD. The mechanisms that account for nonantioxidant effects of AT include the inhibition of protein kinase C, 5-lipoxygenase, tyrosine-kinase as well as cyclooxygenase-2. Based on its antioxidant and anti-inflammatory activities, AT (at the appropriate dose and form) could have beneficial effects on cardiovascular disease in a high-risk population.

Phosphorus leaching at cold temperatures as affected by wastewater application and soil phosphorus levels.

Land application of wastewater in the northern-tier United States during winter months has been suggested as a means to reduce cost of building storage lagoons. A study was initiated in 1996 to assess land application of potato-processing wastewater on a 120-ha field at Park Rapids, MN. One objective of this study was to evaluate the effects of soil P levels and temperature on P leaching in soil columns. In this paper, we report the P sorption, desorption, and leaching characteristics of a high-P (>200 mg kg(-1)) and a low-P (<25 mg kg(-1)) surface soil from the wastewater irrigation site. The leaching experiment was done with wastewater at 4 +/- 2 or 10 +/- 2 degrees C. The high-P soil resulted in an equilibrium P concentration of 8.0 mg L(-1) compared with 0.14 mg L(-1) for the low-P soil. When low-P wastewater was applied to the high-P soil, the soil acted as a P source, and the total phosphorus (TP) concentration in the leachate was 3.5 times higher than the input TP concentration (C0). When high-P wastewater was applied to the high-P soil, the soil acted as a P sink retarding the TP concentration in the leachate by 80%. Phosphorus desorption was higher at 10 degrees C compared with 4 degrees C. The results showed that depending on P levels of the soil and the wastewater, reduction or increase in leachate P will occur below the surface soil. However, further mobility of this P under field conditions will depend on the volume and rate of percolating water as well as the sorption-desorption characteristics of the subsoil.

Antifungal Activity of Nor-securinine Against Some Phytopathogenic Fungi.

Crude extracts and active principles from medicinal plants have shown potential role in controlling plant diseases in glasshouses as well as in fields as one of the safest and ecofriendly methods. The effect of nor-securinine (an alkaloid) isolated from Phyllanthus amarus has been seen against spore germination of some fungi (Alternaria brassicae, A. solani, Curvularia pennisetti, Curvularia sp., Erysiphe pisi, Helminthosporium frumentacei) as well as pea powdery mildew (Erysiphe pisi) under glasshouse conditions. The sensitivity of fungi to nor-securinine varied considerably. Nor-securinine was effective against most of the fungi. H. frumentacei was more sensitive even at the lowest concentration (1,000 µg/ml). Likewise conidia of E. pisi were also inhibited in partially or completely appressorium formation. Pre-inoculation treatment showed greater efficacy than post-inoculation in inhibiting powdery mildew development on pea plants in a glasshouse. Maximum inhibition occurred at 2000 µg/ml.

Investigation on the phenolics of some spices having pharmacotherapeuthic properties.

Spices are an important group of agricultural commodities being used by many civilizations all over the world to aid flavor, taste and nutritional values in the food. In traditional medical systems, their ability to heal various physical, mental and emotional problems has widely been reported. With this view, HPLC analysis was performed to estimate phenolic acids in 21 spices (asafetida, Bishop's weed, black mustard, coriander, cinnamon, clove, curry leaf, cumin black, cumin, fennel, fenugreek, garlic, ginger, Indian cassia, Indian dill or dill large cardamom, onion, saffron, tamarind, true cardamom, yellow mustard) commonly used in India in different forms. In all, 7 phenolic acids; viz., tannic, gallic, caffeic, cinnamic, chlorogenic, ferulic and vanillic acids could be identified on the basis of their retention time with standard compounds and co-chromatography. Several parts of the spices, for instance, seeds, leaves, barks, rhizomes, latex, stigmas, floral buds and modified stems were used in the study. Maximum amount of tannic and gallic acids was observed in black mustard and clove. Caffeic, chlorogenic and ferulic acids were found maximum in cumin while vanillic and cinnamic acids in onion seeds. The spices are known to significantly contribute to the flavor, taste, and medicinal properties of food because of phenolics.

Two plant alkaloids isolated from Corydalis longipes as potential antifungal agents.

The alkaloids N-methylhydrasteine hydroxylactam and 1-methoxyberberine chloride were isolated from Corydalis longipes. Both alkaloids showed high efficacy individually (in concentration of 50-150 ppm) and also in a 1:1 mixture against spore germination of some fungi, viz. Alternaria alternata, A. brassicae, Curvularia maculans, Curvularia sp., Colletotrichum gloeosporioides, Colletotrichum sp., Helminthosporium speciferum, H. pennisetti, Helminthosporium sp., and Ustilago cynodontis. The antifungal effect of single compounds was dose-dependent. If the mutual ratio of the two components in the mixture was changed from 1:1 to a major content of any of the two compounds, the inhibitory effect on spore germination decreased.

Studies on essential oils: part 10; antibacterial activity of volatile oils of some spices.

The essential oils extracted from the seeds of seven spices, Anethum graveolens, Carum capticum, Coriandrum sativum, Cuminum cyminum, Foeniculum vulgare, Pimpinella anisum and Seseli indicum have been studied for antibacterial activity against eight pathogenic bacteria, causing infections in the human body. It has been found that the oil of C. capticum is very effective against all tested bacteria. The oil of C. cyminum and A. graveolens also gave similar results. These oils are equally or more effective when compared with standard antibiotics, at a very low concentration.