Smoking blunts sertraline response in depression: A prospective observational cohort study.

Background: Smoking is common in patients of depression and is known to affect response to antidepressants. This study was undertaken to evaluate the effect of smoking on the antidepressant effect of sertraline. Method: Patients with depression were divided into smoker and nonsmoker cohorts and followed up for 8 weeks. Serum sertraline levels were estimated using the high-performance liquid chromatography system. Response to treatment was evaluated with the Hamilton Depression Rating Scale (HAM-D). Results: Serum sertraline levels did not differ between smokers and nonsmokers at 4 and 8 weeks. Nonsmokers responded better to sertraline than smokers after 8 weeks. Adverse drug reaction profile did not vary between the two groups and was not impacted by serum sertraline levels. Nonsmokers showed a greater fall in the HAM-D score than smokers. Conclusion: This study found depression among smokers to be less responsive to sertraline. This was not explained by serum sertraline levels. Treatment of depression in smokers with sertraline might require higher doses and duration, with more frequent reviews.

Longitudinal study of the course and outcome of first-episode psychosis.

Background: Study of first episode psychosis (FEP), an episode of psychotic nature, which manifests for the first time in an individual in the longitudinal continuum of his/her illness, has been a matter of research interest in recent years, as this may give more insight to the overall phenomenology and course of psychotic illnesses. Methods: A study was undertaken to evaluate course and outcome of first episode psychosis. A total of 100 consecutive inpatients were selected for the study. Informed consent was obtained. Structured Proforma was used for recording psychosocial profiles and relevant medical history. Brief Psychiatric Rating Scale (BPRS) was given to assess the severity of psychopathology; Positive and Negative Symptom Scale (PANSS) to assess the severity of psychosis; Becks Suicidal Ideation Scale (BSI) to assess the extent of suicidality and Global Assessment of Functioning (GAF) to assess global functioning of the individual. The assessment was done at baseline, at six months, and at one year. Results: First episode psychosis constituted around a tenth of the caseload. It commonly affected people in the third decade of life. There was an improvement in 92% of the cases over a year of study. Schizophrenia constituted the majority of first episode psychosis. The history of smoking was relatively higher in acute and transient psychotic disorders. Age inversely correlated with the severity of psychopathology. There was no difference in improvement in psychopathology over time in patients of schizophrenia and related disorder vis--vis other psychotic disorders. Conclusion: Our study did not find any significantly varied sociodemographic factors in the course and outcome of the illness. It also refuted the schism between various types of psychosis based on the current classificatory system. It draws our attention toward the unitary concept of psychosis and is a call to re-think our strategies in the management of psychosis.

Impact of cognitive behavioural intervention on caregiver burden in mothers of children diagnosed with cancer.

Background: Mothers of children diagnosed with cancer are found to have coping difficulties in various studies. Most of the studies were done on parents after their child has been newly diagnosed with malignancy, and very few studies were done on coping skills intervention. Hence, this study has been done to assess the impact of cognitive behavioural intervention on caregiver burden in mothers of children diagnosed with cancer. Methods: Twenty mothers coming to the outpatient department of paediatric oncology from 01 September 2018 to 30 April 2019 were enrolled for the study. The participants were administered General Health Questionnaire, Brief Coping Operation Preference Enquiry Scale, Zung Self-Rating Anxiety Scale, and Coping Inventory for Stressful Situations-21 (CISS-21) Scale. Sixteen sessions of cognitive behavioural intervention were given over 8 weeks to all the participants. Reassessment was done after 3 months by use of the above mentioned scales. Results: Participants' mean anxiety score was 49.40 (standard deviation [SD] ±8.89). They used adaptive (active coping and positive reframing) more than the maladaptive (denial and self-blame) coping strategies. Task- and emotion-focused coping mean score on CISS-21 revealed 19.25 (SD ±6.20) and 18.90 (SD ±5.76), respectively. Reassessment after cognitive behavioural intervention revealed statistically significant improvement in maladaptive coping styles, mean anxiety index score, avoidance, and emotion-focused coping. Conclusion: The study has revealed mild to moderate anxiety and the use of both adaptive and maladaptive coping strategies by participants. There is statistically significant improvement in anxiety, maladaptive coping strategies with cognitive behavioural intervention.

Relative bioavailability of folate from the traditional food plant Moringa oleifera L. as evaluated in a rat model.

Moringa oleifera is an affordable and rich source of dietary folate. Quantification of folate by HPLC showed that 5-formyl-5,6,7,8-tetrahydrofolic acid (502.1 µg/100 g DW) and 5,6,7,8-tetrahydrofolic acid (223.9 µg/100 g DW) as the most dominant forms of folate in M. oleifera leaves. The bioavailability of folate and the effects of folate depletion and repletion on biochemical and molecular markers of folate status were investigated in Wistar rats. Folate deficiency was induced by keeping the animals on a folate deficient diet with 1 % succinyl sulfathiazole (w/w). After the depletion period, animals were repleted with different levels of folic acid and M. oleifera leaves as a source of folate. Feeding the animals on a folate deficient diet for 7 weeks caused a significant (3.4-fold) decrease in serum folate content, compared to non-depleted control animals. Relative bioavailability of folate from dehydrated leaves of M. oleifera was 81.9 %. During folate depletion and repletion, no significant changes in liver glycine N-methyl transferase and 5-methyltetrahydrofolate-homocysteine methyltransferase expression were recorded. In RDA calculations, only 50 % of natural folate is assumed to be bioavailable. Therefore, the bioavailability of folate from Moringa is much higher, suggesting that M. oleifera based food can be used as a significant source of folate.

Surfactant induced aggregation behavior of Merocyanine-540 adsorbed on polymer coated positively charged gold nanoparticles.

Surfactant induced aggregation behavior of Merocyanine 540 adsorbed on polymer (PDD) coated gold nanoparticles (AuNP) is reported. The absorption band of the dye shifts to higher energy in the presence of free polymer and polymer coated AuNP implying aggregation. Addition of a negatively charged surfactant (SDS) induces multiple bands in the extinction spectrum of the dye adsorbed on nanoparticle surface. The highest (460nm) and lowest (564nm) energy bands of the dye become prominent at 10 and >50µM SDS concentrations respectively (dye: 10µM; AuNP: 100-200pM). Based on earlier results the high energy band is likely to originate from dye aggregates and the low energy band is likely to originate from dye monomers. This is attributed to the interplay between polymer-surfactant and polymer-dye interactions at the AuNP surface. The extinction spectra of dye adsorbed at AuNP surface remain unaffected in the presence of a positively charged (CTAB) or a neutral surfactant (Tx-100), at low surfactant concentrations. However at higher surfactant concentrations (>60µM) dye aggregation takes place which is attributed to dye-surfactant interactions. The fluorescence intensity of the dye quenched significantly but its lifetime increased in the presence of polymer coated AuNP. This is attributed to aggregation and reduction in the photoisomerization rate of the dye adsorbed on AuNP surface.

TLX activates MMP-2, promotes self-renewal of tumor spheres in neuroblastoma and correlates with poor patient survival.

Nuclear orphan receptor TLX (Drosophila tailless homolog) is essential for the maintenance of neural stem/progenitor cell self-renewal, but its role in neuroblastoma (NB) is not well understood. Here, we show that TLX is essential for the formation of tumor spheres in three different NB cell lines, when grown in neural stem cell media. We demonstrate that the knock down of TLX in IMR-32 cells diminishes its tumor sphere-forming capacity. In tumor spheres, TLX is coexpressed with the neural progenitor markers Nestin, CD133 and Oct-4. In addition, TLX is coexpressed with the migratory neural progenitor markers CD15 and matrix metalloproteinase-2 (MMP-2) in xenografts of primary NB cells from patients. Subsequently, we show the effect of TLX on the proliferative, invasive and migratory properties of IMR-32 cells. We attribute this to the recruitment of TLX to both MMP-2 and Oct-4 gene promoters, which resulted in the respective gene activation. In support of our findings, we found that TLX expression was high in NB patient tissues when compared with normal peripheral nervous system tissues. Further, the Kaplan-Meier estimator indicated a negative correlation between TLX expression and survival in 88 NB patients. Therefore, our results point at TLX being a crucial player in progression of NB, by promoting self-renewal of NB tumor-initiating cells and altering their migratory and invasive properties.

Effect of dehydration methods on retention of carotenoids, tocopherols, ascorbic acid and antioxidant activity in Moringa oleifera leaves and preparation of a RTE product.

Fresh leaves of M. oleifera plants were analysed for nutritionally important phytoconstituents and feasible commercially used dehydration method were evaluated to preserve these in dehydrated leaves. Trans-lutein, trans-ß-carotene and trans-zeaxanthin were found as the major carotenoids in fresh leaves, accounting for 36.9, 18.2 and 5.5 mg/100 g FW, respectively. Similarly, high amounts of ascorbic acid, α-tocopherol and total phenolic content (271.0, 36.9 and 512.0 mg/100 g FW), respectively were recorded in leaves. α-tocopherol was the most stable vitamin under all drying conditions (86.4 % retention during oven drying), compare to other studied phytoconstituents. Cabinet tray drying was found as efficient as lyophilisation to retain maximum content of total carotenoids (60.1 %), trans-ß-carotene (90.1 %), 13-cis-lutein (93.2 %), and DPPH activity, however, lutein (51.3 %) and ascorbic acid (97.8 %) was best preserved by lyophilisation. During dehydration, significant trans to cis isomerization of ß-carotene and lutein was also recorded. A ready to eat (RTE) chutney powder (adjunct) was developed from dehydrated leaves. The product was evaluated using Quantitative Descriptive Analysis and was accepted with a high overall quality score. The present investigation explores the nutritional potential of M. oleifera leaves and suitable methods of drying that could be useful for processed food formulation.

Dietary iron supplements and Moringa oleifera leaves influence the liver hepcidin messenger RNA expression and biochemical indices of iron status in rats.

In this study, the effects of iron depletion and repletion on biochemical and molecular indices of iron status were investigated in growing male Wistar rats. We hypothesized that iron from Moringa leaves could overcome the effects of iron deficiency and modulate the expression of iron-responsive genes better than conventional iron supplements. Iron deficiency was induced by feeding rats an iron-deficient diet for 10 weeks, whereas control rats were maintained on an iron-sufficient diet (35.0-mg Fe/kg diet). After the depletion period, animals were repleted with different source of iron, in combination with ascorbic acid. Iron deficiency caused a significant (P < .05) decrease in serum iron and ferritin levels by 57% and 40%, respectively, as compared with nondepleted control animals. Significant changes in the expression (0.5- to100-fold) of liver hepcidin (HAMP), transferrin, transferrin receptor-2, hemochromatosis type 2, ferroportin 1, ceruloplasmin, and ferritin-H were recorded in iron-depleted and iron-repleted rats, as compared with nondepleted rats (P < .05). Dietary iron from Moringa leaf was found to be superior compared with ferric citrate in overcoming the effects of iron deficiency in rats. These results suggest that changes in the relative expression of liver hepcidin messenger RNA can be used as a sensitive molecular marker for iron deficiency.

Hyper-Rayleigh scattering from gold nanoparticles: effect of size and shape.

We report hyper-Rayleigh scattering (HRS) properties of gold nanoparticles (GNPs) of five different shapes, quasi-spherical (∼10 and ∼20 nm diameter), rod (aspect ratio ∼2), and branched shapes, tetrapod, flower and star with 800 nm, 150 fs laser excitation. Using ∼10 nm spherical GNPs as reference, the first hyperpolarizability (ß) values were calculated for all other shapes. Star and flower shaped GNPs have the highest hyperpolarizability (∼130 and ∼52 times higher, respectively), while rod and tetrapod shaped GNPs only have modest enhancement (∼7 times), which is similar to ∼20 nm size quasi-spherical particles. These enhancements are attributed to reduced symmetry as well as the presence of sharp tips on GNP surface. When the ß values are normalized with respect to the number of atoms per particle, the flower and star shaped GNPs still have the highest hyperpolarizability values. The polar plots of vertically polarized HRS signal as a function of the angle of polarization of the incoming incident light shows two lobes, indicating that excitation is predominantly dipolar in nature although the size of some GNPs are big enough to show a quadrupolar response. It is believed that the presence of sharp tips at the surface of these large sized GNPs is responsible for the observed dipolar response. This study shows that GNPs having sharp tips might be a better candidate when their nonlinear properties are used for sensing applications.

Effect of curcumin on the diffusion kinetics of a hemicyanine dye, LDS-698, across a lipid bilayer probed by second harmonic spectroscopy.

The diffusion kinetics of a hemicyanine dye, LDS-698, across model membrane bilayers was studied in real time by the surface specific second harmonic technique. Using liposomes made from different headgroups, it has been established that the diffusion is initiated by electrostatic adsorption of the positively charged dye to the outer surface of negatively charged liposomes and its time constant is affected by the rigidity of the bilayer. In the presence of the liphophilic drug curcumin (curcumin/lipid mole ratio ~ 0.2), the diffusion of LDS-698 was observed to be faster by ~56 times (from 780 to 14 s) at 25 °C. Under similar curcumin concentration, when cholesterol containing liposomes are used at 2 °C, the observed diffusion time constant increases from 14 to 65 s, showing that the effect of curcumin is superior to the effect of increasing bilayer rigidity on the diffusion process. Control experiments with other lipophilic molecules such as DPH and Nile Red showed that the effect of liposomal curcumin is superior. Consistent with previous reports of curcumin affecting the bilayer organization, this study additionally demonstrates increased permeability of liposomal curcumin, in particular against organic cations. It is speculated that origin of this enhanced membrane permeability by lipophilic molecules may depend upon the interaction of the molecule with the polar headgroup region of the lipid which, in turn, is expected to depend on the chemical structure of the molecule.

Picosecond spectral relaxation of curcumin excited state in a binary solvent mixture of toluene and methanol.

Picosecond spectral relaxation of the excited state of curcumin in a binary solvent mixture of toluene and MeOH (or MeOH-d4) is reported with an instrument time resolution of ∼40 ps. With increasing mole fraction of MeOH (MeOH-d4) the fluorescence intensity and lifetime of curcumin increase to a maximum at a MeOH (MeOH-d4) mole fraction of 0.14 (0.40) and then decrease. In addition, fluorescence decays taken at the red edge of the emission spectrum started to show measurable rise times (170 to 30 ps), the magnitude of which decreased gradually with increasing alcohol mole fraction. This is attributed to the modulation of the nonradiative rates associated with the excited-state intermolecular H(D) bonding between the pigment and the polar protic solvent. As a consequence, the solvation times in the binary mixture were observed to slow down considerably (20-40 times) at certain solvent compositions compared to neat MeOH. The fact that three Gaussian components are needed to adequately represent the steady-state emission spectra and two isosbestic points are observed in the time-resolved area normalized emission (TRANE) spectra of the pigment suggests the existence of at least three species in the excited state. The observed results are rationalized with a scheme where ground state of the pigment exists in free and H-bonded (intermolecular) state. Optical excitation results in a mixture of these species in the excited state and the observed spectral relaxation correspond to the conversion of these two species in to a third species where dipolar solvation and intermolecular H-bonding have been optimized.

Diffusion of chlorin-p6 across phosphatidyl choline liposome bilayer probed by second harmonic generation.

We have investigated the diffusion of the photosensitizer Chlorin-p(6) (Cp(6)) across a egg lecithin lipid bilayer at different pH by the Second Harmonic Generation (SHG) method. Cp(6) has three ionizable carboxylic acid groups, and consequently, neutral and several ionic forms of Cp(6) are expected to be present in the pH range 3-8. The absorption spectra of Cp(6) get considerably modified in the presence of liposomes as the pH is decreased indicating that the drug liposome binding is pH dependent. The first pK(a) of interconversion (D-C) has been identified at pH ~7.0 by fluorescence measurement in an earlier work. In this work, the second pK(a) of interconversion (C-B) has been identified at pH ~4.8 by the hyper-Rayleigh scattering method. At acidic pH (3, 4, and 5), where species A, B, and C are dominant, the addition of liposomes to a Cp(6) solution generates an instantaneous rise (less than 1 s) in the second harmonic (SH) signal followed by decays whose time constants ranged from ten to hundreds of seconds. The instantaneous rise is attributed to the adsorption of Cp(6) to the outer lipid bilayer, and the decay is attributed to the diffusion of the neutral and charged (A and B) species of the drug. The observed fast and slow time constants for diffusion in the pH range 3-5 are attributed to the neutral (A) and ionic form (B) of Cp(6), respectively. At pH 6, the intensity of the generated SH signals on the addition of liposome reduced, and at physiological pH, it was too weak to be detected. These results are consistent with previous studies that show that the interaction between Cp(6) and egg-PC liposomes is pH dependent. At lower pH due to the presence of the hydrophobic species (A and B) of Cp(6), its interaction with liposomes is strong, and at higher pH, the abundance of the negatively charged hydrophilic species (C and D) decreases the interaction with the like charged liposomes. We have also studied the effect of increasing the bilayer rigidity by decreasing the temperature of the medium or by incorporating 50 mol % cholesterol in the lipid bilayer and observed that lowering of temperature has more profound effect on the diffusion rates. The characteristics of the SH signal changed significantly when liposomes incorporating 50 mol % cholesterol were used at a low (3 °C) temperature. Under these conditions, the SH signal consisted of an instantaneous (<1s) followed by a slower rise (10-90s), and then, it decayed on a much longer time scale. This slow rise of the SH signal at pH 3 and 4 may be attributed to the temperature dependent adsorption of the anionic species (B) of Cp(6) with the liposomes. Further investigations are required in order to understand clearly the pH dependent diffusion of this drug across lipid bilayers.

Efficiency of RAPD, SSR and cytochrome P450 gene based markers in accessing genetic variability amongst finger millet (Eleusine coracana) accessions.

Finger millet (Eleusine coracana L.) is an important crop used for food, forage, and industrial products. Three DNA marker techniques, random amplified polymorphic DNA (RAPD), simple sequence repeat (SSR) and cytochrome P(450) gene based markers were used for the detection of genetic polymorphism in 83 accessions of finger millet collected from various geographical regions of India and Africa. A total of 18 RAPD, 10 SSR and 10 pairs of cytochrome P(450) gene based markers were generated 56.17, 70.19 and 54.29% polymorphism, respectively. Mean polymorphism information content (PIC) for each of these marker systems (0.280 for RAPD, 0.89 for SSR and 0.327 for cytochrome P(450) gene based markers) suggested that SSR marker were highly effective in determining polymorphism. The phenograms based on the three markers data indicate that genotypes from different geographical regions are clearly distinguishable as separate clusters. Mantel test employed for detection of goodness of fit established cophenetic correlation values above 0.90 for all the three marker systems. The dendrograms and PCA plots derived from the binary data matrices of the three marker systems are highly concordant. High bootstrap values were obtained at major nodes of phenograms through WINBOOT software. Based on the results of present study, SSR and cytochrome P(450) gene based markers appear to be particularly useful for the estimation of genetic diversity. This study reveals the potential of RAPD, SSR and gene based markers for characterizing germplasm of Eleusine coracana and narrow down the vast germplasm into distinct core groups.

Chemopreventive effect of nonsteroidal anti-inflammatory drugs on 9,10-dimethylbenz[a]anthracene-induced lung carcinogenesis in mice.

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, celecoxib, and etoricoxib were studied as chemopreventive agents in lung cancer in mice induced by 9,10-dimethylbenz[a]anthracene (DMBA). The animals were subjected to a single intratracheal instillation of DMBA by surgical intervention, while they were treated with oral NSAIDs daily at their following anti-inflammatory dose: aspirin 25 mg/kg, celicoxib 6 mg/kg, and etoricoxib 0.6 mg/kg body weight, respectively. The animals were sacrificed after 18 weeks of treatment. Results showed a significant incidence of pulmonary tumors, dysplastic changes in histopathology, and signs of inflammatory occurrence in the DMBA-treated animals, which were grossly reversed by the NSAIDs. A greater number of macrophages, neutrophils, and lymphocytes were seen in the bronchoalveolar lavage (BAL) smear while the inflammatory cell counts decreased in DMBA + NSAIDs groups. A significant increase in the drug-metabolizing enzymes viz. cytochrome p450, cytochrome b5, and glutathione-S-transferase was noted in the DMBA group, which was reverted back in the NSAID-treated mice. Similarly, the subcelluler enzymes were elevated in DMBA, but significantly fell in the NSAID groups. DMBA also caused a higher level of lipid peroxidation as well as the different antioxidant enzyme activity, which were corrected by the NSAIDs. A marked elevation was noticed in the total lipid composition and its individual constituents in the DMBA group, which was reverted back appreciably by the NSAIDs. The results suggest that the DMBA-induced lung tumor development in balb/c mice could be a reliable model to test the chemopreventive potential of the NSAIDs.

Pulmonary carcinogenesis in mice with a single intratracheal instillation of 9, 10-dimethyl benz[a]anthracene.

A single intratracheal instillation of 9,10-dimethyl benz(a)anthracene (DMBA) at 3 different doses of 5, 10, and 20 mg/kg body weight to Balb/c mice for 12 weeks had caused a significant incidence of pulmonary tumors along with inflammatory changes. The number of macrophages in the broncho-alveolar lavage (BAL) fluid increased significantly, while the neutrophil and lymphocyte count as well as the protein content in the BAL fluid remained unchanged. A marked elevation in the lipid peroxidation product as well as the antioxidative enzymes were noted in the DMBA-treated group. The BAL fluid, which contains the surfactant membrane, was tested for rotational diffusion of the small hydrocarbon fluorophore, diphenyl hexatriene, and resulted in an enhanced fluorescence polarization and anisotropy value as well as the order parameter. DMBA treatment also altered the toxicity parameters, such as the lipid peroxidation, catalase, total protein, reduced glutathione, and alanine and amino transferase activities in the liver and kidney tissues. The results suggest that DMBA-induced lung tumor development in Balb/c mice could be an important model for the study of pathophysiology of BAL-fluid-associated surfactant and offers to test a variety of promising chemopreventive/chemotherapeutic agents.

Livestock farmers' perception and epidemiology of bovine trypanosomosis in Kwale District, Kenya.

We did cross-sectional surveys in Kwale District, Kenya to determine the epidemiology of bovine trypanosomosis and livestock owners' perceptions of the disease. The surveys involved relative importance of trypanosomosis, examination of the current disease constraints, current control practices and drug-use patterns. Informal meetings were held with farmers and cattle census undertaken. Tsetse-fly densities and trypanosomosis prevalences in cattle were determined. A total of 132 farmers were interviewed. Trypanosomosis, anaplasmosis, East Coast fever, foot-and-mouth diseases were reported to be the major constraints to livestock production. Trypanosomosis was the most important compared to other diseases. Chemotherapy was the most widely used method of controlling the disease. Farmer-based tsetse-control technologies were poorly adopted. Respondents were quite knowledgeable on the symptoms, causes and treatment of trypanosomosis. Glossina austeni, G. brevipalpis and G. pallidipes were found in the area; the latter was the most common (0.2-738 flies/trap). Trypanosoma congolense and T. vivax were found in cattle with the former more prevalent. Infection prevalences in cattle varied between 0 and 25% (median: 22%).

Effect of Selenium and alpha-Tocopherol on the Antioxidant Defense System of Goat Erythrocytes and the Hemic System.

ABSTRACT The effect of sodium selenite, alpha-tocopherol, and their combination was studied in the hemic system of goat. Incubation of goat blood with selenium and vitamin E for 24 h resulted in a decrease in hemoglobin concentrations in Se-and vitamin E-treated groups, whereas no change in the osmotic fragility was observed. In plasma the levels of albumin did not show any significant change in all the treatment groups. The acute phase protein (total protein) was found to be increased in the group treated with Se at a concentration of 10 mug, and ceruloplasmin in the plasma was significantly increased in the group supplemented with Se at a concentration of 20 mug. The catalase was found to be increased in both the Se treatment groups and the group that received vitamin E at a concentration of 10 mug. However, the effects on lipid peroxidation, acetylcholinesterase, and antioxidant enzymes such as superoxide dismutase are not significant. The sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) pattern of the proteins did not show any alteration. Also, no effect was observed in the membrane permeability and physicochemical alteration of erythrocytes in the presence of Se and vitamin E.