In vitro targeting and selective killing of mcf-7 and colo320dm cells by 5-fluorouracil anchored to carboxylated SWCNTs and MWCNTs.

The intention of the present work was to synthesize the f-MWCNT and f-SWCNT terminated with proper functional group, loading of 5-Flurouracil and to perform cytotoxic activity. Functionalization of MWCNTs and SWCNTs was achieved through the acid treatment (H2SO4 + HNO3). 5-flurouracil was loaded into the prepared functionalized CNTs, thereafter; in vitro drug loading capacity and % drug release were calculated. Also the prepared f-CNTs, 5-flurouracil loaded CNTs were distinguished by using SEM, TGA, DSC, X-ray diffraction, Raman and FTIR spectroscopy. MCF-7 and COLO320DM cells were treated with selected concentrations of 5-FU loaded f-MWCNTs and f-SWCNTs to estimate the cytotoxic activity. It was observed that 5-FU loaded f-SWCNTs showed good activity against selected cell lines than others. Moreover, apoptosis percentage was reported to be 84.46 ± 4.3515 and 92.78 ± 2.6549 for 5-FU loaded f-SWCNTs against MCF-7 and COLO320DM cells respectively. It is evident from the results that the prepared drug loaded CNTs have comparable antitumor activity in cancer cell lines.

Microwave-assisted combustion synthesis and luminescence properties of colour-tunable Eu3+ /Tb3+ co-doped BaLaB9 O16.

In the present study, hexagonal structured borate phosphors BaLaB9 O16 were prepared using a combustion method with colour-tunable emission properties achieved by varying the doping concentration of Eu3+ and Tb3+ in the cluster. The as-prepared materials were analyzed for structural and morphological parameters through X-ray diffraction (XRD) and field emission scanning electron microscopy (FE-SEM) studies. Tuning of colour was predicted through the photoluminescence and photoluminescence excitation spectra of the materials that showed good green and red emissions when doped with Tb3+ and Eu3+ , respectively, whereas the emission of the co-doped sample (Eu3+ and Tb3+ ) can be varied from the green region to red region by varying the excitation range from 207 to 254 nm.

Determinants of High HIV Infection Prevalence in Vijayapura, Bagalkot, and Belagavi Districts in Karnataka, India.

Introduction India has the second-highest number of people living with human immunodeficiency virus (PLHIV). Despite the national decline in the prevalence of the human immunodeficiency virus (HIV) from 2000 to 2021, regional variations persist, particularly in the northeastern and southern states. High-risk populations, including female sex workers (FSW), men who have sex with men (MSM), and injecting drug users (IDU), significantly contribute to these dynamics. This study focuses on high-prevalence districts in Karnataka. Objectives This study aims to identify socioeconomic and behavioral factors associated with high HIV prevalence in high-burden districts of South Indian states. Methodology A cross-sectional study was conducted using data from Integrated Counseling and Testing Centers (ICTCs) and Designated STI/RTI (sexually transmitted infections/reproductive tract infections) Clinics (DSRCs) across 24 centers in the three districts. The centers were determined using a simple random sampling method. Data from 2501 HIV-positive individuals were analyzed, focusing on demographics, risk behaviors, and treatment history. Results Males constituted the majority of HIV cases, accounting for 448 (56.0%) in Vijayapura, 334 (51.4%) in Bagalkot, and 644 (61.1%) in Belagavi districts, with a significant portion referred by government hospitals. High HIV prevalence was linked to adults aged 25-49 years of age; the number of people with HIV was high among daily wage workers and individuals with multiple sexual partners compared to married and educated people. Newly diagnosed discordant couples ranged from 129 (12.2%) in Belagavi to 133 (18.4%) in Vijayapura districts. Most patients were on first-line antiretroviral therapy (ART), with loss to follow-up attributed to system negligence and poor compliance. Conclusion Key determinants of high HIV prevalence include gender, age, marital status, socioeconomic status, and sexual behavior. Effective interventions require targeted education, improved healthcare services, robust surveillance, and strengthened collaboration among stakeholders.

Prevalence of goitre and iodine deficiency among school children (6-12 years) in rural areas of North Karnataka, India: A cross-sectional survey, 2016-19.

Introduction: Iodine deficiency disorders (IDD) have remained an unresolved public health problem in India. In this survey, we have estimated the prevalence of IDD among 6-12 years of school children in rural areas of north Karnataka, India and estimated the prevalence of low iodine content (<15 ppm) in salt at the household level and urine iodine excretion in this population. Material and Methods: In this cross-sectional survey, we recruited 16,827 children between 6 and 12 years of age through multistage sampling from six districts. Goitre was examined clinically for all children. Household-level salt iodine estimation and urinary iodine estimation were carried out among a subset of the participants. Results: Overall prevalence of goitre was 17.1% (95% CI: 16.5, 17.7). Out of this, 76.7% (n = 2116) had Grade-1 goitre, and 23.7% (n = 656) had Grade-2 goitre. The prevalence of goitre was higher among females (17.9%, vs. male 16.4%, P < 0.05). The prevalence of low iodine content (<15 ppm) in salt was 48.5% (95%CI: 46.7, 50.3). The overall median iodine excretion in urine was 85 µg/L (IQR: 60-150 µg/L). In total, 37.2% (n = 601) had mild iodine deficiency, 5.2% (n = 84) had moderate deficiency, and 10.1% (n = 163) had severe deficiency. All parameters showed high inter- and intradistrict variations. Conclusion: North Karnataka has a high goitre prevalence. Low use of iodized salt can be a major reason for the high prevalence of the condition. Ensuring the availability of iodized salt in this region and periodic surveillance to measure the impact of the programme should be the priority in this region.

Simple ammonium salts acting on sigma-1 receptors yield potential treatments for cancer and depression.

Sigma-1 and sigma-2 receptors are emerging therapeutic targets. We have identified that simple ammonium salts bind to these receptors and are effective in vivo. Radioligand binding assays were used to obtain structure-activity relationships of these salts. MTS assays were performed to determine their effect on growth in MCF7 and MDA-MB-486 cells. Anticancer properties were tested in NMRI mice transplanted with a fragment of mouse adenocarcinoma (MAC13). Antidepressant activity was tested using the forced-swim test and tail suspension tests. Dipentylammonium (Ki 43 nM), tripentylammonium (Ki 15 nM) and trihexylammonium (Ki 9 nM) showed high affinity for the sigma-1 receptor. Dioctanoylammonium had the highest affinity (K50 0.05 nM); this also showed the highest affinity for sigma-2 receptors (Ki 13 nM). Dipentylammonium was found to have antidepressant activity in vivo. Branched-chain ammonium salts showed lower affinity. Bis(2-ethylhexyl)ammonium (K50 29 µM), triisopentylammonium (K50 196 µM) and dioctanoylammonium showed a low Hill slope, and fitted a 2-site binding model for the sigma-1 receptor. We propose this two-site binding can be used to biochemically define a sigma-1 receptor antagonist. Bis(2-ethylhexyl)ammonium and triisopentylammonium were able to inhibit the growth of tumours in vivo. Cheap, simple ammonium salts act as sigma-1 receptor agonists and antagonists in vivo and require further investigation.

Co-administration of nitric oxide (NO) donors prevents haloperidol-induced orofacial dyskinesia, oxidative damage and change in striatal dopamine levels.

Tardive dyskinesia (TD) has been considered as a major clinical issue in the treatment of schizophrenia. Various animal studies have indicated the role of oxidative stress and nitric oxide pathway in haloperidol-induced TD. The present study investigated the effect of NO donors (molsidomine and l-arginine) in haloperidol-induced TD in rats. Chronic administration of haloperidol (1 mg/kg i.p. for 21 days) significantly increased vacuous chewing movements (VCMs), tongue protrusions, and facial jerking in rats which was dose dependently inhibited by NO donors. Besides, haloperidol also increased striatal superoxide anion levels and decreased striatal NO and citrulline levels which were prevented by molsidomine and l-arginine. On chronic administration of haloperidol, there was a decrease in the striatal levels of dopamine, which was again reversed by treatment with NO donors. The findings of the present study suggested for the involvement of NO in the development of neuroleptic-induced TD and indicated the potential of NO donors as a possible therapeutic option. Furthermore, a sub-study on a possible schizophrenic phenotype, i.e. a possible clinical worsening in the animals receiving NO donors and neuroleptics will substantiate the clinical utility of the study.

Anti-depressant like effect of curcumin and its combination with piperine in unpredictable chronic stress-induced behavioral, biochemical and neurochemical changes.

Curcumin, a yellow pigment extracted from rhizomes of the plant Curcuma longa (turmeric), has been widely used as food additive and also as a herbal medicine throughout Asia. The present study was designed to study the pharmacological, biochemical and neurochemical effects of daily administration of curcumin to rats subjected to chronic unpredictable stress. Curcumin treatment (20 and 40 mg/kg, i.p., 21 days) significantly reversed the chronic unpredictable stress-induced behavioral (increase immobility period), biochemical (increase monoamine oxidase activity) and neurochemical (depletion of brain monoamine levels) alterations. The combination of piperine (2.5 mg/kg, i.p., 21 days), a bioavailability enhancer, with curcumin (20 and 40 mg/kg, i.p., 21 days) showed significant potentiation of its anti-immobility, neurotransmitter enhancing (serotonin and dopamine) and monoamine oxidase inhibitory (MAO-A) effects as compared to curcumin effect per se. This study provided a scientific rationale for the use of curcumin and its co-administration with piperine in the treatment of depressive disorders.

In vivo microdialysis studies of striatal level of neurotransmitters after haloperidol and chlorpromazine administration.

Therapeutic success of atypical antipsychotics has focused the attention on the role of receptor systems other than dopaminergic system in the pathophysiology of neuroleptics-associated acute (Parkinson's like syndrome) and chronic (tardive dyskinesia) extrapyramidal side effects. This study was planned to investigate changes in striatal levels of norepinephrine, dopamine and serotonin after acute and chronic administration of classical neuroleptics (haloperidol and chlorpromazine). These changes were correlated with behavioural alterations in rats. In vivo microdialysis with HPLC/ECD system revealed that there was a marked decrease in striatal neurotransmitter contents (NE, DA and 5-HT), which was also correlated with severe cataleptic response in rats after acute administration of haloperidol (2 mg/kg) and chlorpromazine (20 mg/kg). Chronic administration of haloperidol (1 mg/kg for 21 days) and chlorpromazine (5 mg/kg for 21 days) resulted in time dependent increase in orofacial hyperkinetic movements. The microdialysis studies also showed a significant decrease in the striatal levels of all the neurotransmitters. The results provide evidence for the involvement of striatal adrenergic and serotonergic systems, besides dopaminergic system in neuroleptic-induced acute and chronic extrapyramidal symptoms.

Modulatory effect of neurosteroids in haloperidol-induced vacuous chewing movements and related behaviors.

RATIONALE: Tardive dyskinesia is a syndrome of abnormal and involuntary movements which occurs as a complication of long-term neuroleptic therapy especially classical neuroleptics such as haloperidol and chlorpromazine. Dysfunction of GABA receptor mediated inhibition, and increased glutamatergic neurotransmission has been implicated in the development of orofacial dyskinesia in rats and tardive dyskinesia in humans. Neurosteroids modulate both GABAergic as well as glutamatergic neurotransmission in various brain areas. OBJECTIVE: The objective of the present study was to elucidate the role of various neurosteroids in neuroleptic-induced vacuous chewing movements and related behaviors in rats by using behavioral, biochemical, and neurochemical parameters. MATERIALS AND METHODS: Animals chronically treated with haloperidol (1 mg/kg i.p.) for a period of 21 days exhibited marked increase in vacuous chewing movements, tongue protrusions, and facial jerkings as compared to vehicle-treated controls. It also resulted in increased superoxide anion levels and lipid peroxidation, whereas decreased levels of endogenous antioxidant enzymes (catalase and superoxide dismutase) in rat brain striatum homogenates. Neurochemical studies revealed that chronic administration of haloperidol resulted in significant decrease in the levels of dopamine, serotonin, and norepinephrine in rat brain striatum homogenates, whereas urine biogenic amines metabolite levels were increased. In a series of experiments, rats co-administered with allopregnanolone (0.5, 1, and 2 mg/kg i.p.) and progesterone (5, 10, and 20 mg/kg i.p.), both positive GABA-modulating [negative N-methyl-D-aspartate (NMDA)-modulating] neurosteroids prevented, whereas pregnenolone (0.5, 1, and 2 mg/kg i.p.) and dihydroxyepiandrosterone sulfate (0.5, 1, and 2 mg/kg i.p.) both negative GABA-modulating (positive NMDA-modulating) neurosteroids aggravated all the behavioral, biochemical, and neurochemical parameters. CONCLUSIONS: These results suggest that neurosteroids may play a significant role in the pathophysiology of vacuous chewing movements and related behaviors by virtue of their action on either the GABA or NMDA modulation. Furthermore, neurosteroids showing selectivity for positive GABA modulation and/or negative NMDA modulation may be particularly efficacious as novel therapeutic agents for the treatment of tardive dyskinesia and deserve further evaluation.

Antidepressant activity of curcumin: involvement of serotonin and dopamine system.

RATIONALE: Curcumin is a major active principle of Curcuma longa, one of the widely used preparations in the Indian system of medicine. It is known for its diverse biological actions. OBJECTIVE: The present study was designed to investigate the involvement of monoaminergic system(s) in the antidepressant activity of curcumin and the effect of piperine, a bioavailability enhancer, on the bioavailability and biological effects of curcumin. METHODS AND OBSERVATIONS: Behavioral (forced swim test), biochemical (monoamine oxidase (MAO) enzyme inhibitory activity), and neurochemical (neurotransmitter levels estimation) tests were carried out. Curcumin (10-80 mg/kg, i.p.) dose dependently inhibited the immobility period, increased serotonin (5-hydroxytryptamine, 5-HT) as well as dopamine levels (at higher doses), and inhibited the monoamine oxidase enzymes (both MAO-A and MAO-B, higher doses) in mice. Curcumin (20 mg/kg, i.p.) enhanced the anti-immobility effect of subthreshold doses of various antidepressant drugs like fluoxetine, venlafaxine, or bupropion. However, no significant change in the anti-immobility effect of imipramine and desipramine was observed. Furthermore, combination of subthreshold dose of curcumin and various antidepressant drugs resulted in synergistic increase in serotonin (5-HT) levels as compared to their effect per se. There was no change in the norepinephrine levels. The coadministration of piperine (2.5 mg/kg, i.p.), a bioavailability enhancing agent, with curcumin (20 and 40 mg/kg, i.p.) resulted in potentiation of pharmacological, biochemical, and neurochemical activities. CONCLUSION: The study provides evidences for mechanism-based antidepressant actions of curcumin. The coadministration of curcumin along with piperine may prove to be a useful and potent natural antidepressant approach in the management of depression.

Protective effect of L-type calcium channel blockers against haloperidol-induced orofacial dyskinesia: a behavioural, biochemical and neurochemical study.

Haloperidol is a classical neuroleptic drug that is still in use and can lead to abnormal motor activity such as tardive dyskinesia (TD) following repeated administration. TD has no effective therapy yet. There is involvement of calcium in triggering the oxidative damage and excitotoxicity, both of which play central role in haloperidol-induced orofacial dyskinesia and associated alterations. The present study was carried out to investigate the protective effect of calcium channel blockers [verapamil (10 and 20 mg/kg), diltiazem (10 and 20 mg/kg), nifedipine (10 and 20 mg/kg) and nimodipine (10 and 20 mg/kg)] against haloperidol induced orofacial dyskinesia and associated behavioural, biochemical and neurochemical alterations in rats. Chronic administration of haloperidol (1 mg/kg i.p., 21 days) resulted in a significant increase in orofacial dyskinetic movements and significant decrease in % retention, coupled with the marked increase in lipid peroxidation and superoxide anion generation where as significant decrease in non protein thiols and endogenous antioxidant enzyme (SOD and catalase) levels in rat brain striatum homogenates. All these deleterious effects of haloperidol were significantly attenuated by co-administration of different calcium channel blockers. Neurochemically, chronic administration of haloperidol resulted in significant decrease in levels of catecholamines (dopamine, serotonin) and their metabolites (HVA and HIAA) but increased turnover of dopamine and serotonin. Co-administration of most effective doses of verapamil, diltiazem, nifedipine and nimodipine significantly attenuated these neurochemical changes. Results of the present study indicate that haloperidol-induced calcium ion influx is involved in the pathogenesis of tardive dyskinesia and calcium channel blockers should be tested in clinical trials with nifedipine as the most promising one.

Activation of striatal inflammatory mediators and caspase-3 is central to haloperidol-induced orofacial dyskinesia.

The undesired extrapyramidal movement disorders observed with long term treatment with haloperidol have been associated with striatal neurodegeneration. The present study was designed to investigate the effect of prolonged haloperidol treatment on striatal levels of inflammatory mediators and caspase-3 and to correlate it with orofacial dyskinesia, a movement disorder observed with long term haloperidol treatment. Prolonged administration of haloperidol (1, 2, 5 mg/kg) to rats produced dose-dependent increase in the orofacial dyskinetic movements and induced a marked oxidative stress in the striatum. Lower dose of haloperidol (1 mg/kg) decreased NO levels but did not induce TNF-alpha or NF-kappaB expression. At higher doses (2 and 5 mg/kg), increased levels of total nitric oxide and TNF-alpha in cytoplasmic lysate and active p65 subunit of NF-kappaB in nuclear lysates of rat brain were observed. These doses (2 and 5 mg/kg) also induced an increased expression of caspase-3 protein in striatal cytoplasmic fraction as shown by western blot analysis. Collectively, we conclude that oxidative stress mediated increase in inflammatory mediators may initiate the apoptotic pathway (caspase-3) after chronic haloperidol treatment. All this is well correlated with behavioural development of orofacial dyskinesia.

On the mechanism of antidepressant-like action of berberine chloride.

Berberine, an alkaloid isolated from Berberis aristata Linn. has been used in the Indian system of medicines as a stomachic, bitter tonic, antiamoebic and also in the treatment of oriental sores. Evidences have demonstrated that berberine possesses central nervous system activities, particularly the ability to inhibit monoamine oxidase-A, an enzyme involved in the degradation of norepinephrine and serotonin (5-HT). With this background, the present study was carried out to elucidate the antidepressant-like effect of berberine chloride in different behavioural paradigms of despair. Berberine (5, 10, 20 mg/kg, i.p.) inhibited the immobility period in mice in both forced swim and tail-suspension test, however, the effect was not dose-dependent. Berberine (5 and 10 mg/kg, i.p.) also reversed the reserpine-induced behavioral despair. Berberine (5 mg/kg, i.p.) enhanced the anti-immobility effect of subeffective doses of various typical but not atypical antidepressant drugs in forced swim test. Berberine (5 mg/kg, i.p.) following its acute administration in mice resulted in increased levels of norepinephrine (31%), serotonin (47%) and dopamine (31%) in the whole brain. Chronic administration of berberine (5 mg/kg, i.p.) for 15 days significantly increased the levels of norepinephrine (29%), serotonin (19%) as well as dopamine (52%) but at higher dose (10 mg/kg, i.p.), there was no change in the norepinephrine (12%) levels but a significant increase in the serotonin (53%) and dopamine (31%) levels was found. The antidepressant-like effect of berberine (5 mg/kg, i.p.) in forced swim test was prevented by pretreatment with l-arginine (750 mg/kg, i.p.) or sildenafil (5 mg/kg, i.p.). On the contrary, pretreatment of mice with 7-nitroindazole (7-NI) (25 mg/kg, i.p.) or methylene blue (10 mg/kg, i.p.) potentiated the effect of berberine (2 mg/kg, i.p.) in the forced swim test. Pretreatment of mice with (+)-pentazocine (2.5 mg/kg, i.p.), a high-affinity sigma1 receptor agonist, produced synergism with subeffective dose of berberine (2 mg/kg, i.p.). Pretreatment with various sigma receptor antagonists viz. progesterone (10 mg/kg, s.c.), rimcazole (5 mg/kg, i.p.) and N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine (BD1047; 1 mg/kg, i.p.) reversed the anti-immobility effects of berberine (5 mg/kg, i.p.). Berberine at lower dose did not affect the locomotor activity and barbiturate-induced sleep time. It produced mild hypothermic action in rats and displayed analgesic effect in mice. Taken together, theses findings demonstrate that berberine exerted antidepressant-like effect in various behavioural paradigms of despair possibly by modulating brain biogenic amines (norepinephrine, serotonin and dopamine). Further, nitric oxide pathway and/or sigma receptors are involved in mediating its antidepressant-like activity in mouse forced swim test.

Progesterone attenuates neuroleptic-induced orofacial dyskinesia via the activity of its metabolite, allopregnanolone, a positive GABA(A) modulating neurosteroid.

GABAergic hypofunction in the basal ganglia is stated as an important mechanism underlying the pathophysiology of tardive dyskinesia. In the present study we sought to establish the protective effect of progesterone in haloperidol-induced orofacial dyskinesia. Besides this we also tried to find out whether the GABA(A) facilitatory action of progesterone metabolites is responsible for the action of progesterone in attenuating the haloperidol-induced orofacial dyskinesia, an animal model of tardive dyskinesia. Chronic administration of haloperidol (1 mg/kg, i.p. 21 days) induced significant increase in hyperkinetic orofacial dyskinetic movements and oxidative damage in the brain as compared to control group. Coadministration of progesterone (5-20 mg/kg, i.p. 21 days) dose dependently prevented the hyperkinetic orofacial movements as well as oxidative damage parameters. The protective activity of progesterone was reversed by pre treatment with finasteride (50 mg/kg i.p.), a 5alpha-reductase inhibitor that blocks the metabolism of progesterone to allopregnanolone and other metabolites. Further, chronic administration of haloperidol resulted in significant decrease in dopamine levels in rat striatum homogenates and increase in catecholamine metabolite levels. Coadministration of progesterone also reversed the decrease in dopamine levels induced by chronic haloperidol treatment, an effect which was again reversed by pre treatment with finasteride. Our study provides strong evidence that the protective effect of progesterone resides in the GABAergic as well as neuroprotective activity of its metabolite allopregnanolone. These findings lend support to recognized GABA hypofunction theory of tardive dyskinesia and strongly suggest progesterone as a protective therapy in this debilitating movement disorder.

Differential striatal levels of TNF-alpha, NFkappaB p65 subunit and dopamine with chronic typical and atypical neuroleptic treatment: role in orofacial dyskinesia.

Long term use of typical neuroleptics such as haloperidol may be limited by unwanted motor side effects like tardive dyskinesia characterized by repetitive involuntary movements, involving the mouth, face and trunk. Atypical neuroleptics, such as clozapine and risperidone are devoid of these side effects. However the precise mechanisms of the neuronal toxicity induced by haloperidol are poorly understood. It is possible that typical and atypical antipsychotic differently affects neuronal survival and death and that these effects considerably contribute to the differences in the development of TD. The aim of the present study is to investigate the role of TNF-alpha and NFkappaB on the toxicity induced by chronic haloperidol administration in an animal model of tardive dyskinesia. Rats were treated for 21 days with: haloperidol (5 mg/kg), clozapine (5 and 10 mg/kg), risperidone (5 mg/kg) or saline. Orofacial dyskinetic movements and total locomotor activity was evaluated. Striatal levels of dopamine were measure by HPLC/ED whereas striatal levels of TNF-alpha and NFkappaB p65 subunit were measured by ELISA technique. Haloperidol increased orofacial dyskinetic movements and total locomotor activity (on day 22) (P

Licofelone: the answer to unmet needs in osteoarthritis therapy?

Licofelone, a competitive inhibitor of cyclooxygenases 1 and 2 and 5-lipoxygenase enzyme, is under clinical evaluation for its effectiveness in the treatment of osteoarthritis (OA). Licofelone decreases the production of both prostaglandins and leukotrienes and has been shown to possess a combination of analgesic or anti-inflammatory effects with a promising gastrotolerability profile. Available clinical data have shown that licofelone is at least as effective as the conventional nonsteroidal anti-inflammatory drugs or coxibs in ameliorating the symptoms of OA, but it may offer the advantage of improved gastrotolerability and fewer or no incidences of worsened peripheral edema. Last, further evidence suggests that it could be a suitable alternative for the long-term treatment of a wide population of patients with OA. The preset review describes the status of licofelone in the treatment of OA.

Protective effect of Curcumin, the active principle of turmeric (Curcuma longa) in haloperidol-induced orofacial dyskinesia and associated behavioural, biochemical and neurochemical changes in rat brain.

Tardive dyskinesia (TD) is a motor disorder of the orofacial region resulting from chronic neuroleptic treatment. A high incidence and irreversibility of this hyperkinetic disorder has been considered a major clinical issue in the treatment of schizophrenia. The molecular mechanism related to the pathophysiology of tardive dyskinesia is not completely known. Various animal studies have demonstrated an enhanced oxidative stress and increased glutamatergic transmission as well as inhibition in the glutamate uptake after the chronic administration of haloperidol. The present study investigated the effect of curcumin, an antioxidant, in haloperidol-induced tardive dyskinesia by using different behavioural (orofacial dyskinetic movements, stereotypy, locomotor activity, % retention), biochemical (lipid peroxidation, reduced glutathione levels, antioxidant enzyme levels (SOD and catalase) and neurochemical (neurotransmitter levels) parameters. Chronic administration of haloperidol (1 mg/kg i.p. for 21 days) significantly increased vacuous chewing movements (VCM's), tongue protrusions, facial jerking in rats which was dose-dependently inhibited by curcumin. Chronic administration of haloperidol also resulted in increased dopamine receptor sensitivity as evident by increased locomotor activity and stereotypy and also decreased % retention time on elevated plus maze paradigm. Pretreatment with curcumin reversed these behavioral changes. Besides, haloperidol also induced oxidative damage in all major regions of brain which was attenuated by curcumin, especially in the subcortical region containing striatum. On chronic administration of haloperidol, there was a decrease in turnover of dopamine, serotonin and norepinephrine in both cortical and subcortical regions which was again dose-dependently reversed by treatment with curcumin. The findings of the present study suggested for the involvement of free radicals in the development of neuroleptic-induced tardive dyskinesia and point to curcumin as a possible therapeutic option to treat this hyperkinetic movement disorder.

Development and validation of an RP-HPLC method for the estimation of adenosine and related purines in brain tissues of rats.

A new, rapid and sensitive RP-HPLC method with UV spectrophotometric detection was developed and validated for the concomitant estimation of adenosine and related purines in rat brain tissue preparations. The HPLC system consisted of C-18 column with UV-photodiode-array detection ranging from 210 to 400 nm, facilitating the online confirmation of peak purity. The column temperature was maintained at 30 degrees C and the injection volume was 20 muL. Elution with an isocratic mobile phase consisting of water/methanol/acetonitrile (88:5:7 by volume) at a flow rate of 0.8 mL/min yielded sharp, utmost-resolved peaks of adenosine (Ade), inosine (Ino), hypoxanthine (Hypoxan) and adenine (Adn) within 10 min. The method was validated with respect to the linearity, accuracy, precision, sensitivity, selectivity and stability. The method was also employed to estimate the naturally occurring purines in discrete regions of rat brain. A new protocol developed for tissue preparation utilizing H(2)SO(4) and Tris buffer gave well-resolved peaks and high component recoveries (>96%) which eliminated the need of an internal standard. The results show that the method for the determination of Ade, Ino, Hypoxan and Adn by RP-HPLC described here has good linearity, accuracy, precision, sensitivity, selectivity and is simple and rapid to perform.

Comparative behavioural profile of newer antianxiety drugs on different mazes.

Anxiety is associated with diverse range of psychiatric conditions. In the present study, antianxiety effect of fluoxetine, citalopram (SSRI's), gabapentin (antiepileptic drugs), venlafaxine (SNRI), clozapine and resperidone (atypical antipsychotics) and a herbal preparation ashwagandha on elevated zero maze and elevated plus maze paradigms was examined. Anti-anxiety potentials of these drugs were compared with diazepam. The drugs tested i.e. fluoxetine (10 mg/kg), citalopram (10 mg/kg), clozapine (0.25, 0.5, 1 mg/kg), resperidone.(0.5, 1 mg/kg), venlafaxine (4, 8, 16 mg/kg), citalopram (10 mg/kg), fluoxetine (10 mg/kg), gabapentin (10, 20 mg/kg) and ashwagandha (100, 200 mg/kg) significantly increased the number of open arm entries and time spent in open arm. These drugs also decreased the latency to enter in open arm as compared to control in both the paradigms. Present study confirms the antianxiety activity of different newer classes of drugs and found some of them comparable to diazepam in both the elevated zero maze and elevated plus maze paradigm.

Possible involvement of L-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling pathway in the antidepressant activity of berberine chloride.

Berberine is an isoquinoline alkaloid isolated from Berberis aristata, a major herb widely used in Indian and Chinese systems of medicine. Berberine possessed a wide range of biological activity including antidiarrheal, antimicrobial, anti-inflammatory effects and some central nervous system activity as well. The present study was designed to explore the antidepressant activity and its possible mechanism of action. Further, the involvement of L-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling pathway in the antidepressant action of berberine chloride was investigated. The antidepressant activity was assessed in forced-swim and tail-suspension tests. Total immobility period was recorded during a six-min test. Berberine (5-20 mg/kg, i.p.) produced a reduction in immobility period in both the tests. When berberine (5 mg/kg, i.p.) was co-administered with other antidepressant drugs, it enhanced the anti-immobility effect of subeffective doses of imipramine (2 mg/kg, i.p.), desipramine (5 mg/kg, i.p.), tranylcypromine (4 mg/kg, i.p.), fluoxetine (5 mg/kg, i.p.), venlafaxine (2 mg/kg, i.p.) or bupropion (10 mg/kg, i.p.) in forced-swim test. However, berberine did not modify the effects of mianserine (32 mg/kg, i.p.) or trazodone (2 mg/kg, i.p.), the two atypical antidepressant drugs. The neurochemical analysis revealed that berberine (5 mg/kg, i.p.) increased the levels of norepinephrine, serotonin or dopamine in the mouse whole brain. The antidepressant-like effect of berberine (5 mg/kg, i.p.) in forced-swim test was prevented by pretreatment with L-arginine (750 mg/kg, i.p.) [substrate for nitric oxide synthase (NOS)]. Pretreatment of mice with 7-nitroindazole (25 mg/kg, i.p.) [a specific neuronal nitric oxide synthase (nNOS) inhibitor] produced potentiation of the action of subeffective dose of berberine (2 mg/kg, i.p.). In addition, treatment of mice with methylene blue (10 mg/kg, i.p.) [direct inhibitor of both nitric oxide synthase (NOS) and soluble guanylate cyclase (sGC)] potentiated the effect of berberine (2 mg/kg, i.p.) in the forced-swim test. Furthermore, the reduction in the immobility period elicited by berberine (5 mg/kg, i.p.) was also inhibited by pretreatment with sildenafil (5 mg/kg, i.p.) [phosphodiesterase 5 inhibitor]. The various modulators and their combination with berberine did not produce any changes in locomotor activity. Our findings demonstrated that berberine exerted antidepressant-like effect in various behavioural paradigms of despair possibly by modulating brain biogenic amines (norepinephrine, serotonin or dopamine) and further, the antidepressant-like effect of berberine in the forced-swim test involved an interaction with the L-arginine-NO-cGMP pathway.