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1.
Transl Psychiatry ; 11(1): 54, 2021 01 14.
Article in English | MEDLINE | ID: mdl-33446638

ABSTRACT

Neurodevelopmental abnormalities in neural connectivity have been long implicated in the etiology of schizophrenia (SCZ); however, it remains unclear whether these neural connectivity patterns are associated with genetic risk for SCZ in unaffected individuals (i.e., an absence of clinical features of SCZ or a family history of SCZ). We examine whether polygenic risk scores (PRS) for SCZ are associated with functional neural connectivity in adolescents and young adults without SCZ, whether this association is moderated by sex and age, and if similar associations are observed for genetically related neuropsychiatric PRS. One-thousand four-hundred twenty-six offspring from 913 families, unaffected with SCZ, were drawn from the Collaborative Study of the Genetics of Alcoholism (COGA) prospective cohort (median age at first interview = 15.6 (12-26), 51.6% female, 98.1% European American, 41% with a family history of alcohol dependence). Participants were followed longitudinally with resting-state EEG connectivity (i.e., coherence) assessed every two years. Higher SCZ PRS were associated with elevated theta (3-7 Hz) and alpha (7-12 Hz) EEG coherence. Associations differed by sex and age; the most robust associations were observed between PRS and parietal-occipital, central-parietal, and frontal-parietal alpha coherence among males between ages 15-19 (B: 0.15-0.21, p < 10-4). Significant associations among EEG coherence and Bipolar and Depression PRS were observed, but differed from SCZ PRS in terms of sex, age, and topography. Findings reveal that polygenic risk for SCZ is robustly associated with increased functional neural connectivity among young adults without a SCZ diagnosis. Striking differences were observed between men and women throughout development, mapping onto key periods of risk for the onset of psychotic illness and underlining the critical importance of examining sex differences in associations with neuropsychiatric PRS across development.


Subject(s)
Bipolar Disorder , Schizophrenia , Adolescent , Adult , Bipolar Disorder/genetics , Depression , Female , Genetic Predisposition to Disease , Humans , Male , Prospective Studies , Schizophrenia/genetics , Sex Characteristics , Young Adult
2.
Dalton Trans ; 49(14): 4502-4517, 2020 Apr 07.
Article in English | MEDLINE | ID: mdl-32193522

ABSTRACT

NiCr2-xFexO4 (x = 0 and 0.2) polycrystalline ceramics have been synthesized successfully through a simple co-precipitation technique to study the evolution of structural and magnetic properties by doping Fe. X-ray diffraction (XRD) reveals that the high-temperature cubic phase (space group Fd3[combining macron]m) observed at 320 K in bulk NiCr2O4 is stabilized at room temperature by decreasing the particle size to nanometer in x = 0 as well as after incorporating 20 at% Fe in the NiCr2O4 lattice. The cation distribution obtained from X-ray absorption fine structure (XAFS) analysis illustrates that while in x = 0, Ni2+ and Cr3+ ions occupy the tetrahedral (A) and octahedral (B) sites, respectively, x = 0.2, Fe3+ and Cr3+ ions occupy the A and B sites, respectively, and Ni2+ ions are distributed among the A and B sites. This transformation from the normal to mixed spinel structure strongly affects the magnetic properties. While the paramagnetic to long-range ferrimagnetic ordering temperature TC is enhanced from 71 to 192 K, significantly large coercive field (HC) of ∼29 kOe is observed for x = 0.2 as compared to the HC ∼13 kOe for x = 0. Moreover, unusually large conventional and spontaneous exchange bias fields of ∼26 and ∼2.6 kOe are observed for x = 0.2, which is absent for x = 0. The presence of anomalous exchange bias field is ascribed to the unidirectional exchange anisotropy between the two magnetic sublattices at A and B sites. The training effect of the exchange bias field is discussed using a phenomenological model, which considers the contribution from irreversible uncompensated spins that modify the exchange anisotropy at the interface between A and B magnetic sublattices. In addition, diffuse neutron scattering (DNS) with XYZ analysis is employed for both compositions to clearly illustrate the low-temperature peculiar magnetic phase transitions such as spin spiral transition, TS and spin lock-in transition, Tl. The DNS demonstrates that while Tl decreases from 10 K to 7 K with the incorporation of Fe in the NiCr2O4 lattice, TS significantly increases from 28 K to 50 K.

3.
Indian J Nephrol ; 28(3): 220-225, 2018.
Article in English | MEDLINE | ID: mdl-29962673

ABSTRACT

Hepatitis C virus (HCV) infection in renal allograft recipient is associated with increased morbidity and mortality. At present, only few studies related to treatment and outcomes of HCV-infected renal allograft recipients with DAAs have been published. We aimed the study to assess the efficacy and safety of sofosbuvir-based regimens in HCV-infected renal allograft recipients. We analyzed data of 22 eligible HCV-infected renal allograft recipients (14 genotype-3, 6 genotype-1, one each genotype-2 and 4) who were treated with DAAs at our institute. DAA regimen included sofosbuvir and ribavirin with or without ledipasvir or daclatasvir for 12-24 weeks. Patients were followed up for 24 weeks after completion of treatment. A rapid viral response of 91%, end of therapy response of 100%, and sustained viral response at 12 and 24 weeks of 100% with rapid normalization of liver enzymes were observed. Therapy was well tolerated except for ribavirin-related anemia. A significant decrease in tacrolimus trough levels was observed and most patients required increase in tacrolimus dose during the study. Treatment with newer DAAs is effective and safe for the treatment of HCV-infected renal allograft recipients.

4.
Transbound Emerg Dis ; 65(1): 114-122, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28299893

ABSTRACT

During 2013-2015, several and severe outbreaks of African swine fever (ASF) affected domestic pigs in six provinces of Zambia. Genetic characterization of ASF viruses (ASFVs) using standardized genotyping procedures revealed that genotypes I, II and XIV were associated with these outbreaks. Molecular and epidemiological data suggest that genotype II ASFV (Georgia 2007/1-like) detected in Northern Province of Zambia may have been introduced from neighbouring Tanzania. Also, a genotype II virus detected in Eastern Province of Zambia showed a p54 phylogenetic relationship that was inconsistent with that of p72, underscoring the genetic variability of ASFVs. While it appears genotype II viruses detected in Zambia arose from a domestic pig cycle, genotypes I and XIV possibly emerged from a sylvatic cycle. Overall, this study demonstrates the co-circulation of multiple genotypes of ASFVs, involvement of both the sylvatic and domestic pig cycle in ASF outbreaks in Zambia and possible trans-boundary spread of the disease in south-eastern Africa. Indeed, while there is need for regional or international concerted efforts in the control of ASF, understanding pig marketing practices, pig population dynamics, pig housing and rearing systems and community engagement will be important considerations when designing future prevention and control strategies of this disease in Zambia.


Subject(s)
African Swine Fever Virus/isolation & purification , African Swine Fever/virology , Disease Outbreaks/veterinary , Genes, Viral/genetics , Genotype , Sus scrofa/virology , African Swine Fever/epidemiology , African Swine Fever Virus/genetics , Animals , DNA, Viral/genetics , Phylogeny , Polymerase Chain Reaction/veterinary , Sequence Analysis, DNA/veterinary , Swine , Viral Proteins/genetics , Zambia/epidemiology
5.
Enzymes ; 40: 31-64, 2016.
Article in English | MEDLINE | ID: mdl-27776782

ABSTRACT

At any given time and location, plants encounter a flood of environmental stimuli. Diverse signal transduction pathways sense these stimuli and generate a diverse array of responses. Calcium (Ca2+) is generated as a second messenger due to these stimuli and is responsible for transducing the signals downstream in the pathway. A large number of Ca2+ sensor-responder components are responsible for Ca2+ signaling in plants. The sensor-responder complexes calcineurin B-like protein (CBL) and CBL-interacting protein kinases (CIPKs) are pivotal players in Ca2+-mediated signaling. The CIPKs are the protein kinases and hence mediate signal transduction mainly by the process of protein phosphorylation. Elaborate studies conducted in Arabidopsis have shown the involvement of CBL-CIPK complexes in abiotic and biotic stresses, and nutrient deficiency. Additionally, studies in crop plants have also indicated their role in the similar responses. In this chapter, we review the current literature on the CBL and CIPK network, shedding light into the enzymatic property and mechanism of action of CBL-CIPK complexes. We also summarize various reports on the functional modulation of the downstream targets by the CBL-CIPK modules across all plant species.


Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/metabolism , Calcium-Binding Proteins/metabolism , Protein Serine-Threonine Kinases/metabolism , Stress, Physiological , Phosphorylation
6.
J Environ Biol ; 37(2): 179-84, 2016 Mar.
Article in English | MEDLINE | ID: mdl-27097435

ABSTRACT

Biochemical profiling of physiologically mature fruits of 51 diverse Indian gooseberry (Emblica officinalis Gaertn) germplasm accessions was collected from Vindhyan hill region of Madhya Pradesh, with a view to select nutraceutically rich genotypes based on important biochemical traits. The mean ascorbic acid and total phenol (tannin) content amongst different accessions was recorded as 496.47 mg 100 g⁻¹ and 4.88% with highest value found in CISH A-12 (654.50 mg 100 g⁻¹) and CISH A-30 (7.18%), respectively. Apart from the above, wide range of variability in the composition of other important biochemical attributes viz., total soluble solids (8.60-17.70°Brix), acidity (1.61-2.94%), total sugar (4.15-9.17), reducing sugar (2.19-4.45%) and TSS/acid ratio (3.89-8.33) was also recorded. Highest significant and positive correlation was observed between total sugar and TSS (0.895) followed by reducing sugar and TSS (0.882). Significant positive correlation between ascorbic acid and tannins (0.551) was an indication to be associated with binding capacity of ascorbic acid over a longer period of storage.


Subject(s)
Genetic Variation , Phyllanthus emblica/genetics , Phyllanthus emblica/metabolism , Fruit/anatomy & histology , Fruit/chemistry , Gene Expression Regulation, Plant
7.
Indian J Nephrol ; 25(5): 316, 2015.
Article in English | MEDLINE | ID: mdl-26628802
8.
Phys Chem Chem Phys ; 17(44): 30090-101, 2015 Nov 28.
Article in English | MEDLINE | ID: mdl-26499748

ABSTRACT

All scale hierarchical architecturing, matrix/inclusion band alignment and intra-matrix electronic structure engineering, the so called panoscopic approach for thermoelectric materials has been demonstrated to be an effective paradigm for optimizing high ZT. To achieve such hierarchically organized microstructures, composition engineering has been considered to be an efficient strategy. In this work, such a panoscopic concept has been extended to demonstrate for the first time in the case of half-Heusler based thermoelectric materials via a composition engineering route. A series of new off-stoichiometric n-type Zr0.7Hf0.3Ni1+xSn (0 ≤x≤ 0.10) HH compositions have been modified to derive HH(1 -x)/full-Heusler (FH)(x) composite with an all scale hierarchically modified microstructure with FH inclusions within the matrix to study the temperature dependent thermoelectric properties. The structural analysis employing XRD, FE-SEM and HR-TEM of these materials reveal a composite of HH and FH, with hierarchically organized microstructures. In such a submicron/nano-composite, the electronic properties are observed to be well optimized yielding a large power factor; α(2)σ (∼30.7 × 10(-4) W m(-1) K(-2) for Zr0.7Hf0.3Ni1.03Sn) and reduced thermal conductivity (∼2.4 W m(-1) K(-1) for Zr0.7Hf0.3Ni1.03Sn) yielding a high ZT∼ 0.96 at 773 K for composition Zr0.7Hf0.3Ni1.03Sn which is ∼250% larger than the normal HH Zr0.7Hf0.3NiSn (ZT∼ 0.27 at 773 K). The enhancement in ZT of these composites has been discussed in terms of primary electron filtering, electron injection and several phonon scattering mechanisms such as alloy scattering, point defect scattering, and grain boundary scattering. The Bergman and Fel model is used to calculate effective thermoelectric parameters of these composites for comparing the experimental results.

9.
Neuroscience ; 299: 1-17, 2015 Jul 23.
Article in English | MEDLINE | ID: mdl-25934039

ABSTRACT

BACKGROUND: Expression of the neuronal membrane glycoprotein M6a (GPM6A), the proteolipid protein (PLP/DM20) family member, is downregulated in the hippocampus of chronically stressed animals. Its neuroplastic function involves a role in neurite formation, filopodium outgrowth and synaptogenesis through an unknown mechanism. Disruptions in neuroplasticity mechanisms have been shown to play a significant part in the etiology of depression. Thus, the current investigation examined whether GPM6A expression is also altered in human depressed brain. METHODS: Expression levels and coexpression patterns of GPM6A, GPM6B, and PLP1 (two other members of PLP/DM20 family) as well as of the neuroplasticity-related genes identified to associate with GPM6A were determined using quantitative polymerase chain reaction (qPCR) in postmortem samples from the hippocampus (n = 18) and the prefrontal cortex (PFC) (n = 25) of depressed suicide victims and compared with control subjects (hippocampus n = 18; PFC n = 25). Neuroplasticity-related proteins that form complexes with GPM6A were identified by coimmunoprecipitation technique followed by mass spectrometry. RESULTS: Results indicated transcriptional downregulation of GPM6A and GPM6B in the hippocampus of depressed suicides. The expression level of calcium/calmodulin-dependent protein kinase II alpha (CAMK2A) and coronin1A (CORO1A) was also significantly decreased. Subsequent analysis of coexpression patterns demonstrated coordinated gene expression in the hippocampus and in the PFC indicating that the function of these genes might be coregulated in the human brain. However, in the brain of depressed suicides this coordinated response was disrupted. CONCLUSIONS: Disruption of coordinated gene expression as well as abnormalities in GPM6A and GPM6B expression and expression of the components of GPM6A complexes were detected in the brain of depressed suicides.


Subject(s)
Depressive Disorder, Major/metabolism , Gene Expression , Hippocampus/metabolism , Neuronal Plasticity/genetics , Prefrontal Cortex/metabolism , Suicide , Adaptor Proteins, Signal Transducing/metabolism , Adult , Aged , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Cell Cycle Proteins/metabolism , Depressive Disorder, Major/genetics , Female , Humans , Male , Membrane Glycoproteins/genetics , Membrane Glycoproteins/metabolism , Microfilament Proteins/metabolism , Middle Aged , Myelin Proteolipid Protein/genetics , Myelin Proteolipid Protein/metabolism , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Young Adult
10.
Antimicrob Agents Chemother ; 59(4): 2153-68, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25645848

ABSTRACT

Quorum sensing (QS) regulates group behaviors of Candida albicans such as biofilm, hyphal growth, and virulence factors. The sesquiterpene alcohol farnesol, a QS molecule produced by C. albicans, is known to regulate the expression of virulence weapons of this fungus. Fluconazole (FCZ) is a broad-spectrum antifungal drug that is used for the treatment of C. albicans infections. While FCZ can be cytotoxic at high concentrations, our results show that at much lower concentrations, quercetin (QC), a dietary flavonoid isolated from an edible lichen (Usnea longissima), can be implemented as a sensitizing agent for FCZ-resistant C. albicans NBC099, enhancing the efficacy of FCZ. QC enhanced FCZ-mediated cell killing of NBC099 and also induced cell death. These experiments indicated that the combined application of both drugs was FCZ dose dependent rather than QC dose dependent. In addition, we found that QC strongly suppressed the production of virulence weapons-biofilm formation, hyphal development, phospholipase, proteinase, esterase, and hemolytic activity. Treatment with QC also increased FCZ-mediated cell death in NBC099 biofilms. Interestingly, we also found that QC enhances the anticandidal activity of FCZ by inducing apoptotic cell death. We have also established that this sensitization is reliant on the farnesol response generated by QC. Molecular docking studies also support this conclusion and suggest that QC can form hydrogen bonds with Gln969, Thr1105, Ser1108, Arg1109, Asn1110, and Gly1061 in the ATP binding pocket of adenylate cyclase. Thus, this QS-mediated combined sensitizer (QC)-anticandidal agent (FCZ) strategy may be a novel way to enhance the efficacy of FCZ-based therapy of C. albicans infections.


Subject(s)
Antifungal Agents/pharmacology , Antioxidants/pharmacology , Apoptosis/drug effects , Candida albicans/drug effects , Drug Resistance, Fungal/drug effects , Fluconazole/pharmacology , Quercetin/pharmacology , Quorum Sensing/drug effects , Biofilms/drug effects , Hyphae/drug effects , Microbial Sensitivity Tests , Usnea/chemistry , Virulence Factors/metabolism
11.
Haemophilia ; 21(2): 210-218, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25470321

ABSTRACT

Inhibitors are an impediment to the effective management of haemophilia B (HB), but there is limited understanding of the underlying genetic risk factors. In this study we aim to understand the role of F9 gene mutations on inhibitor development in patients with HB. Mutations in the F9 gene were identified and HLA typing performed for five boys with severe HB. Data from the CDC Haemophilia B Mutation Project (CHBMP) database were used to assess association between F9 gene mutation type and inhibitor development. Analysis of the CHBMP database showed that larger disruptions in the F9 gene are associated with a higher life-time prevalence of inhibitors. We detected the following mutations in the five subjects, including four novel mutations: Nonsense in three patients (c.223 C>T; p.Arg75* in two siblings, c.553 C>T; p.Glu185*); Splice site in two patients (c.723 + 1 G>A, c.278-27 A>G); Missense in one patient (c.580 A>G, p.Thr194Ala; c.723 G>T; p.Gln241His). Of the two siblings only one responded to immune tolerance induction (ITI). These siblings have identical F9 gene mutations but differ with respect to the HLA alleles. Interestingly, an analysis of peptide-MHC binding affinities shows a significantly higher (one-sided unpaired t-test, P = 0.0018) median affinity for FIX-derived peptides in the sibling that responded to ITI. We conclude that the nature of the F9 gene mutation may be an important risk factor for the development of inhibitors. In addition, the HLA alleles of the individual patients, in conjunction with the mutation type, could be a predictor for the development of inhibitors as well as the response to ITI.


Subject(s)
Factor IX/genetics , Factor IX/immunology , Hemophilia B/genetics , Hemophilia B/immunology , Isoantibodies/immunology , Adolescent , Child , Computational Biology , Databases, Factual , Exons , Factor IX/therapeutic use , Genetic Association Studies , Genetic Markers , HLA-DRB1 Chains/genetics , HLA-DRB1 Chains/immunology , Hemophilia B/diagnosis , Hemophilia B/drug therapy , Humans , Male , Mutation , Odds Ratio , RNA Splicing , Severity of Illness Index , Young Adult
12.
J Nanosci Nanotechnol ; 14(9): 6606-13, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25924306

ABSTRACT

The synthesis of amphiphilic noble metal nanoparticles involving the functional role of 3-aminopropyltrimethoxysilane (3-APTMS) and 3-glycidoxypropyltrimethoxy-silane (3-GPTMS) is reported herein. The mechanistic approach on the reactivity of these functional alkoxysilane for the typical controlled synthesis of AuNPs as evidenced from UV-visible spectroscopy and transmission electron microscopy (TEM) is reported. The experimental findings demonstrate the followings; (1) Methanolic solution of 3-GPTMS undergo interaction with 3-APTMS and the same is facilitated in the presence of 3-APTMS treated noble metal ions, (2) The molar ratio of 3-GPTMS/3-APTMS control the nanogeometry as well as the dispersibility of AuNPs in both aqueous and non-aqueous media, (3) the dispersion ability of nanoparticles is found to be based on the hydrophobic alkyl chain of the reaction product of 3-GPTMS and 3-APTMS, and (4) AuNPs shows absorption maxima as a function of polarity and refractive index of the medium. A typical application of as synthesized AuNPs as peroxidase mimetic is reported.

13.
Physiol Mol Biol Plants ; 17(3): 223-9, 2011 Jul.
Article in English | MEDLINE | ID: mdl-23573013

ABSTRACT

A field experiment was conducted to study the impact of solar UV-B (280-315 nm) and UV-A (315-400 nm) components on the growth and antioxidant enzyme activity in cotton plant (Gossypium hirsutum var. Vikram). Solar UV components were excluded by filtering the sunlight through selective UV-B (<315 nm) and UV-B/A (<400 nm) absorbing polyester films. Plants grown under filters that transmitted solar UV served as controls. Exclusion of UV-B and UV-B/A enhanced plant height, leaf area and total biomass of plants. The activity of antioxidant enzymes superoxide dismutase (SOD), ascorbic acid peroxidase (APX), glutathione reductase (GR) and guaiacol peroxidase (GPx) assayed in the leaves were lesser in the UV excluded plants. The level of ascorbic acid and UV absorbing substances were also decreased by the exclusion of UV. Solar UV components exerted a limitation on the potential growth of cotton plants. Reduction in the antioxidant enzyme activity and ascorbic acid after UV exclusion indicated that ambient UV components exert a significant stress on cotton plants. Reduction in the production of UAS indicated a changed pattern of metabolism leading to improved primary metabolism. Exclusion of UV components is advantageous from the agricultural point to enhance the growth of cotton plants.

15.
J Interpers Violence ; 24(7): 1175-91, 2009 Jul.
Article in English | MEDLINE | ID: mdl-18840848

ABSTRACT

A cross-sectional study in a representative sample of 751 women, living in slums, examined their perspectives on partner and relationship factors of domestic violence. More than 17% of women experienced physical violence in the past year. Individual factors related to the husband-namely, poor socioeconomic status, use of alcohol, extramarital relations, and visiting red light districts-increased the risk of violence. The following relationship factors were associated with a higher risk of violence: age difference of 5 years or less between spouses, husband's irregular contribution to family expenses, not sharing information about his personal expenses, manifestation of controlling behaviors, and longer duration of marriage. The study concludes that adverse socioeconomic conditions create low self-esteem and insecurity among men, who find expression in aberrant behaviors, and violence is used as a compensatory behavior. Interventions, therefore, need to go beyond the victim-centric approach and address partner and relationship issues for greater impact.


Subject(s)
Battered Women/statistics & numerical data , Poverty/statistics & numerical data , Spouse Abuse/statistics & numerical data , Spouses/statistics & numerical data , Urban Population/statistics & numerical data , Women's Health , Adult , Battered Women/psychology , Cross-Sectional Studies , Female , Humans , India/epidemiology , Marriage/statistics & numerical data , Middle Aged , Prevalence , Risk Factors , Self Concept , Socioeconomic Factors , Spouse Abuse/psychology , Spouses/psychology , Surveys and Questionnaires , Young Adult
16.
Pak J Pharm Sci ; 21(3): 241-8, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18614419

ABSTRACT

The buccal region offers an attractive route of administration for systemic drug delivery. Carvedilol (dose, 3.125-25 mg) is beta-adrenergic antagonist. Its oral bioavailability is 25-35% because of first pass metabolism. Buccal absorption studies of a carvedilol solution in human volunteers showed 32.86% drug absorption. FTIR and UV spectroscopic methods revealed that there was no interaction between carvedilol and polymers. Carvedilol patches were prepared using HPMC, carbopol 934, eudragit RS 100, and ethylcellulose. The patches were evaluated for their thickness uniformity, folding endurance, weight uniformity, content uniformity, swelling behaviour, tensile strength, and surface pH. In vitro release studies were conducted for carvedilol-loaded patches in phosphate buffer (pH, 6.6) solution. Patches exhibited drug release in the range of 86.26 to 98.32% in 90 min. Data of in vitro release from patches were fit to different equations and kinetic models to explain release profiles. Kinetic models used were zero and first-order equations, Hixon-Crowell, Higuchi, and Korsmeyer-Peppas models. In vivo drug release studies in rabbits showed 90.85% of drug release from HPMC-carbopol patch while it was 74.63 to 88.02% within 90 min in human volunteers. Good correlation among in vitro release and in vivo release of carvedilol was observed.


Subject(s)
Adrenergic beta-Antagonists/pharmacokinetics , Carbazoles/pharmacokinetics , Mouth Mucosa/metabolism , Propanolamines/pharmacokinetics , Acrylates/chemistry , Acrylic Resins , Administration, Buccal , Adrenergic beta-Antagonists/administration & dosage , Adrenergic beta-Antagonists/chemistry , Adult , Animals , Carbazoles/administration & dosage , Carbazoles/chemistry , Carvedilol , Cellulose/analogs & derivatives , Cellulose/chemistry , Chemistry, Pharmaceutical , Dosage Forms , Drug Carriers , Drug Compounding , Drug Stability , Drug Storage , Humans , Hydrogen-Ion Concentration , Hypromellose Derivatives , Male , Methylcellulose/analogs & derivatives , Methylcellulose/chemistry , Propanolamines/administration & dosage , Propanolamines/chemistry , Rabbits , Solubility , Surface Properties , Technology, Pharmaceutical/methods , Tensile Strength , Viscosity
17.
Neuroscience ; 139(3): 1017-29, 2006.
Article in English | MEDLINE | ID: mdl-16500030

ABSTRACT

Earlier studies have implicated brain-derived neurotrophic factor in stress and in the mechanism of action of antidepressants. It has been shown that antidepressants upregulate, whereas corticosterone downregulates, brain-derived neurotrophic factor expression in rat brain. Whether various classes of antidepressants reverse corticosterone-mediated downregulation of brain-derived neurotrophic factor is unclear. Also not known is how antidepressants or corticosterone regulates brain-derived neurotrophic factor expression. To clarify this, we examined the effects of various classes of antidepressants and corticosterone, alone and in combination, on the mRNA expression of total brain-derived neurotrophic factor and of individual brain-derived neurotrophic factor exons, in rat brain. Normal or corticosterone pellet-implanted (100 mg, 21 days) rats were injected with different classes of antidepressants, fluoxetine, desipramine, or phenelzine, intraperitoneally for 21 days and killed 2 h after the last injection. mRNA expression of total brain-derived neurotrophic factor and of exons I-IV was measured in frontal cortex and hippocampus. Given to normal rats, fluoxetine increased total brain-derived neurotrophic factor mRNA only in hippocampus, whereas desipramine or phenelzine increased brain-derived neurotrophic factor mRNA in both frontal cortex and hippocampus. When specific exons were examined, desipramine increased expression of exons I and III in both brain areas, whereas phenelzine increased exon I in both frontal cortex and hippocampus but exon IV only in hippocampus. On the other hand, fluoxetine increased only exon II in hippocampus. Corticosterone treatment of normal rats decreased expression of total brain-derived neurotrophic factor mRNA in both brain areas, specifically decreasing exons II and IV. Treatment with desipramine or phenelzine of corticosterone pellet-implanted rats reversed the corticosterone-induced decrease in total brain-derived neurotrophic factor expression in both brain areas; however, fluoxetine reversed the decrease only partially in hippocampus. Interestingly, antidepressant treatment of corticosterone pellet-implanted rats increased only those specific exons that are increased during treatment of normal rats with each particular antidepressant. We found that although corticosterone and antidepressants both modulate brain-derived neurotrophic factor expression, and antidepressants reverse the corticosterone-induced brain-derived neurotrophic factor decrease, antidepressants and corticosterone differ in how they regulate the expression of brain-derived neurotrophic factor exon(s).


Subject(s)
Antidepressive Agents/pharmacology , Brain-Derived Neurotrophic Factor/drug effects , Brain/drug effects , Corticosterone/pharmacology , Animals , Brain/metabolism , Brain-Derived Neurotrophic Factor/genetics , Brain-Derived Neurotrophic Factor/metabolism , Corticosterone/administration & dosage , Corticosterone/blood , Desipramine/pharmacology , Drug Implants , Exons , Fluoxetine/pharmacology , Gene Expression/drug effects , Male , Phenelzine/pharmacology , RNA, Messenger/analysis , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Transcription, Genetic/drug effects
18.
Mol Psychiatry ; 11(1): 86-98, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16172610

ABSTRACT

The Raf kinases Raf-1 and B-Raf are upstream activators of the extracellular signal-regulated kinase (ERK)-signaling pathway and therefore participates in many physiological functions in brain, including neuronal survival and synaptic plasticity. Previously, we observed that activation of ERK-1/2, the downstream component of ERK signaling, is significantly reduced in post-mortem brain of suicide victims. The present study was undertaken to further examine whether suicide brain is also associated with abnormalities in upstream molecules in ERK signaling. The study was performed in prefrontal cortex (PFC) and hippocampus obtained from 28 suicide victims and 21 normal controls. mRNA levels of Raf-1, B-Raf, and cyclophilin were measured by quantitative RT-PCR. Protein levels of Raf-1 and B-Raf were determined by Western blot, whereas their catalytic activities were determined by immunoprecipitation and enzymatic assays. It was observed that the catalytic activity of B-Raf was significantly reduced in PFC and hippocampus of suicide subjects. This decrease was associated with a decrease in its protein, but not mRNA, level. On the other hand, catalytic activity, and mRNA and protein levels, of Raf-1 were not altered in post-mortem brain of suicide subjects. The observed changes were not related to confounding variables; however, Raf-1 showed a negative correlation with age. Also, the changes in B-Raf were present in all suicide subjects, irrespective of psychiatric diagnosis. Our results of selective reduction in catalytic activity and expression of B-Raf but not Raf-1 suggest that B-Raf may be playing an important role in altered ERK signaling in brain of suicide subjects, and thus in the pathophysiology of suicide.


Subject(s)
Depressive Disorder/physiopathology , MAP Kinase Signaling System/physiology , Proto-Oncogene Proteins B-raf/metabolism , Proto-Oncogene Proteins c-raf/metabolism , Suicide , Adult , Aged , Aged, 80 and over , Antidepressive Agents/therapeutic use , Depressive Disorder/drug therapy , Depressive Disorder/metabolism , Enzyme Activation , Extracellular Signal-Regulated MAP Kinases/metabolism , Female , Hippocampus/physiology , Humans , Male , Middle Aged , Prefrontal Cortex/physiology , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins c-raf/genetics , RNA, Messenger/analysis
20.
Appl Microbiol Biotechnol ; 68(3): 417-24, 2005 Aug.
Article in English | MEDLINE | ID: mdl-15806356

ABSTRACT

p-Nitrophenol (PNP), a toxic nitroaromatic compound, can build up in soils due to extensive usage of nitrophenolic pesticides and hence needs to be removed. Arthrobacter protophormiae RKJ100, a PNP-degrading organism, was used in this work to study factors affecting its growth, and then evaluated for its capacity to degrade PNP in soil microcosms. Molasses (10%) treated with 0.1% potassium hexacyanoferrate was found to be a suitable and cheap carbon source for inoculum preparation. Induction studies showed that PNP depletion was quicker when cells were induced by pre-exposure to PNP. The efficiency of PNP degradation in soil by strain RKJ100 was seen to be dependent on pH, temperature, initial PNP concentration and inoculum size. Microcosm studies performed with varying concentrations (1.4-210 ppm) of PNP-spiked soils showed that strain RKJ100 could effectively degrade PNP over the range 1.4-140 ppm. A cell density of 2x10(8) colony forming units/g soil was found to be suitable for PNP degradation over a temperature range of 20-40 degrees C and at a slightly alkaline pH (7.5). Our results indicate that strain RKJ100 has potential for use in in situ bioremediation of PNP-contaminated sites. This is a model study that could be used for decontamination of sites contaminated also with other compounds.


Subject(s)
Arthrobacter/metabolism , Nitrophenols/metabolism , Soil Pollutants/metabolism , Arthrobacter/growth & development , Biodegradation, Environmental , Culture Media , Hydrogen-Ion Concentration , Temperature , Time Factors
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