Immobilization of the Aspartate Ammonia-Lyase from Pseudomonas fluorescens R124 on Magnetic Nanoparticles: Characterization and Kinetics.

Aspartate ammonia-lyases (AALs) catalyze the non-oxidative elimination of ammonia from l-aspartate to give fumarate and ammonia. In this work the AAL coding gene from Pseudomonas fluorescens R124 was identified, isolated, and cloned into the pET-15b expression vector and expressed in E. coli. The purified enzyme (PfAAL) showed optimal activity at pH 8.8, Michaelis-Menten kinetics in the ammonia elimination from l-aspartate, and no strong dependence on divalent metal ions for its activity. The purified PfAAL was covalently immobilized on epoxy-functionalized magnetic nanoparticles (MNP), and effective kinetics of the immobilized PfAAL-MNP was compared to the native solution form. Glycerol addition significantly enhanced the storability of PfAAL-MNP. Inhibiting effect of the growing viscosity (modulated by addition of glycerol or glucose) on the enzymatic activity was observed for the native and immobilized form of PfAAL, as previously described for other free enzymes. The storage stability and recyclability of PfAAL-MNP is promising for further biocatalytic applications.

Proportion of patients without mental disorders being treated in mental health services worldwide.

BACKGROUND: Previous research suggests that many people receiving mental health treatment do not meet criteria for a mental disorder but are rather 'the worried well'. AIMS: To examine the association of past-year mental health treatment with DSM-IV disorders. METHOD: The World Health Organization's World Mental Health (WMH) Surveys interviewed community samples of adults in 23 countries (n = 62 305) about DSM-IV disorders and treatment in the past 12 months for problems with emotions, alcohol or drugs. RESULTS: Roughly half (52%) of people who received treatment met criteria for a past-year DSM-IV disorder, an additional 18% for a lifetime disorder and an additional 13% for other indicators of need (multiple subthreshold disorders, recent stressors or suicidal behaviours). Dose-response associations were found between number of indicators of need and treatment. CONCLUSIONS: The vast majority of treatment in the WMH countries goes to patients with mental disorders or other problems expected to benefit from treatment.

Associations between DSM-IV mental disorders and diabetes mellitus: a role for impulse control disorders and depression.

AIMS/HYPOTHESIS: No studies have evaluated whether the frequently observed associations between depression and diabetes could reflect the presence of comorbid psychiatric conditions and their associations with diabetes. We therefore examined the associations between a wide range of pre-existing Diagnostic Statistical Manual, 4th edition (DSM-IV) mental disorders with self-reported diagnosis of diabetes. METHODS: We performed a series of cross-sectional face-to-face household surveys of community-dwelling adults (n = 52,095) in 19 countries. The World Health Organization Composite International Diagnostic Interview retrospectively assessed lifetime prevalence and age at onset of 16 DSM-IV mental disorders. Diabetes was indicated by self-report of physician's diagnosis together with its timing. We analysed the associations between all mental disorders and diabetes, without and with comorbidity adjustment. RESULTS: We identified 2,580 cases of adult-onset diabetes mellitus (21 years +). Although all 16 DSM-IV disorders were associated with diabetes diagnosis in bivariate models, only depression (OR 1.3; 95% CI 1.1, 1.5), intermittent explosive disorder (OR 1.6; 95% CI 1.1, 2.1), binge eating disorder (OR 2.6; 95% CI 1.7, 4.0) and bulimia nervosa (OR 2.1; 95% CI 1.3, 3.4) remained after comorbidity adjustment. CONCLUSIONS/INTERPRETATION: Depression and impulse control disorders (eating disorders in particular) were significantly associated with diabetes diagnosis after comorbidity adjustment. These findings support the focus on depression as having a role in diabetes onset, but suggest that this focus may be extended towards impulse control disorders. Acknowledging the comorbidity of mental disorders is important in determining the associations between mental disorders and subsequent diabetes.

Major depressive disorder subtypes to predict long-term course.

BACKGROUND: Variation in the course of major depressive disorder (MDD) is not strongly predicted by existing subtype distinctions. A new subtyping approach is considered here. METHODS: Two data mining techniques, ensemble recursive partitioning and Lasso generalized linear models (GLMs), followed by k-means cluster analysis are used to search for subtypes based on index episode symptoms predicting subsequent MDD course in the World Mental Health (WMH) surveys. The WMH surveys are community surveys in 16 countries. Lifetime DSM-IV MDD was reported by 8,261 respondents. Retrospectively reported outcomes included measures of persistence (number of years with an episode, number of years with an episode lasting most of the year) and severity (hospitalization for MDD, disability due to MDD). RESULTS: Recursive partitioning found significant clusters defined by the conjunctions of early onset, suicidality, and anxiety (irritability, panic, nervousness-worry-anxiety) during the index episode. GLMs found additional associations involving a number of individual symptoms. Predicted values of the four outcomes were strongly correlated. Cluster analysis of these predicted values found three clusters having consistently high, intermediate, or low predicted scores across all outcomes. The high-risk cluster (30.0% of respondents) accounted for 52.9-69.7% of high persistence and severity, and it was most strongly predicted by index episode severe dysphoria, suicidality, anxiety, and early onset. A total symptom count, in comparison, was not a significant predictor. CONCLUSIONS: Despite being based on retrospective reports, results suggest that useful MDD subtyping distinctions can be made using data mining methods. Further studies are needed to test and expand these results with prospective data.

Efficacy of Biomarkers in Predicting Anastomotic Leakage After Gastrointestinal Resection: A Systematic Review and Meta-Analysis.

Our systematic review and meta-analysis were designed to evaluate the published literature from 2016 to 2019 on which the role of biomarkers in predicting the anastomotic leakage (AL) in gastroesophageal cancer surgery was investigated. This extensive literature search was conducted on the principles of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), and Excerpta Medica dataBASE (EMBASE) were used to gather the relevant information. No restrictions were made on the type of biomarkers. Wald or likelihood ratio (LRT) fixed effect tests were used to estimate the pooled prevalence to generate the proportions with 95% confidence intervals (CI) and model-fitted weights. For analyzing heterogeneity, the Cochran Q test and I square test were used. The Egger regression asymmetry test and funnel plot were used for publication. In this meta-analysis, a total of 15 studies were recruited with 1892 patients undergoing the resection. The pooled elevated C-reactive protein (CRP) was observed as 13.9% ranging from 11.6% to 16.1%. The pooled prevalence of other biomarkers with AL was observed as 4.4%. Significant heterogeneity was observed between studies that reported CRP and other biomarkers (92% each with chi-squared values of 78.80 and 122.78, respectively). However, no significant publication was observed between studies (p=0.61 and p=0.11, respectively). We concluded our study on this note that different biomarkers are involved in the diagnosis of AL. However, all these biomarkers are poor predictors with insufficient predictive value and sensitivity.

Study on Hydroxychloroquinine Sulfate Being Given to the Admitted COVID -19 Positive Patients at Institute of JLNMCH, Bhagalpur, Bihar, India.

Background As the global death toll from new coronavirus illness (COVID-19) rises, the scientific community and healthcare systems are under massive pressure to manage the outbreak and develop effective medical remedies. Meanwhile, desperation has pushed practitioners, scientists, and authorities to recommend and attempt medicines with little or no proof. Despite the lack of clear and unequivocal facts supporting its efficacy and safety, hydroxychloroquine-sulfate (HCQS) has recently received substantial public and political interest in treating and prophylaxis new infectious diseases COVID-19. Aim To analyze the impact of HCQS in COVID-19-positive patients admitted at tertiary level government-owned Jawaharlal Nehru Medical College and Hospital (JLNMCH, Bhagalpur) Bihar. Methods Two hundred two RT-PCR-positive COVID-19 patients were included in this research. The study participants were randomly distributed into the intervention category and control category, each consisting of 101 study subjects. Study participants in the intervention category were administered hydroxychloroquine in 200 mg tablets. The control category was given placebo tablets that looked similar to tablets of hydroxychloroquine and were given in the same pattern. Chest X-ray PA view, 12 lead ECG, baseline hemogram including a concentration of CD4 cells, ratio between the concentration of CD8 cells and CD4 cells and concentration of CD8 cells, the concentration of C-reactive protein, RT PCR test of samples obtained from the oropharyngeal region and nasopharyngeal region nasopharyngeal for verification COVID-19 were done. These measurements were carried out in both the control and intervention categories at baseline and at the moment of obtaining a negative RT-PCR report. Results The confirmed cases of COVID-19 was 52.9% in the intervention category and 53.4% in the control category at the end of the administration of drugs. Symptoms related to COVID-19 were observed in 11.6% of subjects in the intervention category and 13.5% in the control category. Other new symptoms were observed in 16.8% of subjects in the intervention category and 14.5% of study subjects in the control category. One death was reported in the control category. Emergency hospitalization was required for one subject in the intervention category, while two subjects in the control category required emergency hospitalization. 12.4 days was the mean duration of recovery in the intervention category, while 13.6 days were the mean duration of recovery in the control category. The recovery duration and COVID-related symptoms were lesser in the intervention category than in the control category; however, the variation between the two categories was statistically non-significant (p˃0.01). Conclusion According to this research, no statistically significant difference was noticed in COVID-19 incidence between the control category and intervention category, showing that hydroxychloroquine sulfate cannot be utilized as the main curative agent in the treatment of COVID-19. However, there was a reduction in recovery days and symptoms related to COVID-19 in study subjects administered with HCQS.

Effectiveness and Safety of Pirfenidone and Nintedanib for Pulmonary Fibrosis in COVID-19-Induced Severe Pneumonia: An Interventional Study.

Background After a diagnosis of two to five years, the survival length for pulmonary fibrosis (PF) is considered to be medium. The primary objective of PF treatment is to stabilize or minimize the pace of progression of the illness. The treatment of PF by nintedanib and pirfenidone was a breakthrough. In a group of coronavirus disease 2019 (COVID-19)-induced PF patients, we examined the efficacy of pirfenidone and nintedanib. Methodology From May 2021 to April 2022, 5,000 patients receiving antifibrotic treatment with pirfenidone or nintedanib (mean age of 78.3 ± 23.8) for PF were identified. Their clinical and functional information was retrospectively examined at zero, six, and twelve months of therapy. Results The average age of patients receiving nintedanib was greater than the average age of the pirfenidone group (p < 0.0001). Exertional dyspnea and dry cough, with no distinction between the two groups, were the most prevalent symptoms of the illness (p < 0.05). No significant changes between patients on pirfenidone and nintedanib were seen in forced vital capacity, forced expiratory volume in one second, total lung capacity, and diffusing capacity for carbon monoxide at zero or six months (p > 0.05). After one year, lung function measures were similar to the baseline in individuals treated with pirfenidone and nintedanib. This study highlights the appearance of both antifibrotic medicines as promising treatment options for functional stability in COVID-19-induced PF patients. Conclusions The patients affected by COVID-19 and undergoing fibrinolytic therapy may be well treated by any of the drugs with a significant improvement.

Trust-Based Smart Contract for Automated Agent to Agent Communication.

Blockchain technology is now regarded as one of the most interesting and possibly innovative technologies. It enables information to be stored and exchanged securely and transparently without the need for a centralized authority to regulate it. Some of the primary benefits of this technology are the atomicity of the stored data. Given its features, this technology has the potential to provide answers to challenges encountered in a very sensitive sector, namely, Internet of Vehicles (IoV). In IoV, vehicles and service providers autonomously capture and produce data without human intervention. This exchanged data must meet certain criteria such as decentralization, automation, security, and stakeholder trust management. To overcome these challenges, the integration of blockchain technology and multi-agent systems is a key solution. Based on smart contracts, the proposed solution consists of exploiting role-based access control (RBAC) and attribute-based access control (ABAC) techniques. This solution removes the central authority (CA) to reduce maintenance costs and eliminate legacy threats from centralized systems. The results, obtained from consumption costs, show that the developed platform is characterized by security, availability, and privacy.

ResNet-50 for 12-Lead Electrocardiogram Automated Diagnosis.

Nowadays, the implementation of Artificial Intelligence (AI) in medical diagnosis has attracted major attention within both the academic literature and industrial sector. AI would include deep learning (DL) models, where these models have been achieving a spectacular performance in healthcare applications. According to the World Health Organization (WHO), in 2020 there were around 25.6 million people who died from cardiovascular diseases (CVD). Thus, this paper aims to shad the light on cardiology since it is widely considered as one of the most important in medicine field. The paper develops an efficient DL model for automatic diagnosis of 12-lead electrocardiogram (ECG) signals with 27 classes, including 26 types of CVD and a normal sinus rhythm. The proposed model consists of Residual Neural Network (ResNet-50). An experimental work has been conducted using combined public databases from the USA, China, and Germany as a proof-of-concept. Simulation results of the proposed model have achieved an accuracy of 97.63% and a precision of 89.67%. The achieved results are validated against the actual values in the recent literature.

Role of PDT as an adjunct to SRP on whole salivary RANKL and OPG ratio in type-2 diabetic and normoglycemic individuals with chronic periodontitis.

OBJECTIVE: The aim was to assess the effect of scaling and root planing (SRP) with and without adjunct photodynamic therapy (PDT) on the levels of osteoprotegerin (OPG) receptor activator of NF-kappa B ligand (RANKL) in the unstimulated whole saliva (UWS) of type-2 diabetic and normoglycemic individuals with chronic periodontitis (CP). METHODS: Type-2 diabetic and normoglycemic subjects with CP (Groups 1 and 2, respectively) were divided into test- (SRP + PDT) and control (SRP only) groups. Patient demographics were recorded; and periodontal parameters (marginal bone loss [MBL], probing depth [P.D], plaque index [PI], gingival index [GI], and clinical attachment loss [CAL]) were assessed at baseline and at 3-months-follow-up. Rate of flow of unstimulated whole saliva and levels of RANKL and osteoprotegerin were measured at both time intervals. P < 0.05 was considered statistically significant. RESULTS: Eighty-four persons with CP (42 with and 42 without type-2 DM) were included. At baseline, clinicoradiographic parameters were comparable in all groups. At 3-months of follow-up, there was no significant difference in the clinicoradiographic parameters in all groups. At 3-months of follow-up, there was no significant reduction in whole salivary RANKL and osteoprotegerin levels among individuals in the test and control groups among CP patients with and without CP. CONCLUSION: The whole salivary RANKL/OPG ratio remains high in patients with poorly-controlled type-2 DM after SRP with or without adjunct PDT.

Childhood adversities and adult psychopathology in the WHO World Mental Health Surveys.

BACKGROUND: Although significant associations of childhood adversities with adult mental disorders are widely documented, most studies focus on single childhood adversities predicting single disorders. AIMS: To examine joint associations of 12 childhood adversities with first onset of 20 DSM-IV disorders in World Mental Health (WMH) Surveys in 21 countries. METHOD: Nationally or regionally representative surveys of 51 945 adults assessed childhood adversities and lifetime DSM-IV disorders with the WHO Composite International Diagnostic Interview (CIDI). RESULTS: Childhood adversities were highly prevalent and interrelated. Childhood adversities associated with maladaptive family functioning (e.g. parental mental illness, child abuse, neglect) were the strongest predictors of disorders. Co-occurring childhood adversities associated with maladaptive family functioning had significant subadditive predictive associations and little specificity across disorders. Childhood adversities account for 29.8% of all disorders across countries. CONCLUSIONS: Childhood adversities have strong associations with all classes of disorders at all life-course stages in all groups of WMH countries. Long-term associations imply the existence of as-yet undetermined mediators.

Kohl (surma): retrospect and prospect.

Kohl, since antiquity has always been given a prime importance in ophthalmology for the protection and treatment of various eye ailments. However, for decades various conflicting reports in the literature have been published relating to Kohl application to eyes being responsible for causing higher blood lead concentration, which may cause lead poisoning. While at the same time, a number of research studies and reports have also been published negating any such links with increased blood lead level upon Kohl (surma) application. In view of the above mentioned facts, this review article is written with the objective to highlight various data from past and present research studies and reports about Kohl, so as to provide valuable information to both the users and the research workers about it's scientific background and effects when applied into eyes. A large number of items and topics (such as Kohl, surma, eye cosmetic, traditional eye preparations, environmental lead pollution, galena, lead sulphide etc.) have been taken into consideration while compiling this review article. In conclusion, the authors of this review article feel that the relation between Kohl and toxicity or increased blood lead concentration upon it's application to eyes as reported elsewhere is likely to be more of theoretical nature rather than a practical health hazard.

Associations between DSM-IV mental disorders and subsequent onset of arthritis.

OBJECTIVE: We investigated the associations between DSM-IV mental disorders and subsequent arthritis onset, with and without mental disorder comorbidity adjustment. We aimed to determine whether specific types of mental disorders and increasing numbers of mental disorders were associated with the onset of arthritis later in life. METHOD: Data were collected using face-to-face household surveys, conducted in 19 countries from different regions of the world (n=52,095). Lifetime prevalence and age at onset of 16 DSM-IV mental disorders were assessed retrospectively with the World Health Organization (WHO) Composite International Diagnostic Interview (WHO-CIDI). Arthritis was assessed by self-report of lifetime history of arthritis and age at onset. Survival analyses estimated the association of initial onset of mental disorders with subsequent onset of arthritis. RESULTS: After adjusting for comorbidity, the number of mood, anxiety, impulse-control, and substance disorders remained significantly associated with arthritis onset showing odds ratios (ORs) ranging from 1.2 to 1.4. Additionally, the risk of developing arthritis increased as the number of mental disorders increased from one to five or more disorders. CONCLUSION: This study suggests links between mental disorders and subsequent arthritis onset using a large, multi-country dataset. These associations lend support to the idea that it may be possible to reduce the severity of mental disorder-arthritis comorbidity through early identification and effective treatment of mental disorders.

Biopharmaceutical evaluation of oral tablet Atenolol (100 and 50 mg) on local population.

An open-label, randomized study was designed to determine the bioavailability (BA); pharmacokinetic (PK) and pharmacodynamic (PD) behaviour of Atenolol 50 mg (two pills) and 100 mg (one pill) tablet manufactured by a national pharmaceutical industry. Peak plasma concentration (Cmax): 1.33 +/- 0.31 microg/ml, time to peak plasma concentration (Tmax): 2.2 +/- 0.27 hours, AUC (area under the plasma concentration-time curve) 6.34 +/- 2.1 microg-hr/ml for 100 mg tab and Cmax: 1.07 +/- 0.23 microg/ml, Tmax: 2.5 +/- 0.35 hours, AUC 4.97 +/- 1.09 microg-hr/ml for 50 mg (two pills) tab were observed. The BA and PK parameters such as Cmax, Tmax, are comparable to previous studies, although significant decrease in diastolic and systolic blood pressure (mmHg) upto a certain limit for a considerable duration was observed. However, relation between PK and PD may not be established due to regulatory biochemical feedback mechanism.

Effects of tryptophan and valine administration on behavioral pharmacology of haloperidol.

Development of antipsychotics with slight/no extra-pyramidal symptoms (EPS) and/or other side effects is one of the exploring fields of drug research. Haloperidol is a high potency typical neuroleptic used in the treatment of schizophrenia but produces muscles related side effects commonly known as EPS. These effects are not produced following the administration of atypical neuroleptics such as clozapine. A severe side effect of clozapine treatment is however, agranulocytosis. This involves investigation on the mechanism by which a typical neuroleptic acting via serotonergic mechanism tends to produce less or no EPS. The present study was, therefore, designed to determine the effect of serotonin precursor tryptophan and a large neutral amino acid other than tryptophan (valine) on the modulation of haloperidol induced catalepsy and akinesia. Cataleptic effects of the drug and activity reducing effects were monitored on inclined surface and in an activity box or open field respectively. The results are discussed in the context of a role of tryptophan and valine induced changes of brain serotonin in modifying the extrapyramidal and monoaminergic effects of the typical neuroleptic haloperidol. In the present study administration of TRP and valine decreased activity in rats, haloperidol-induced catalepsy' was not modulated by prior administration of tryptophan or valine. Brain serotonin levels were elevated by haloperidol treatment and correlated very well with the behavioral response. These findings suggest a possible serotonergic involvement in neuroleptic induced tardive dyskinesia and an amelioration of the disorder through TRP supplementation.

The Epidemiology of Major Depressive Episode in the Iraqi General Population.

OBJECTIVE: To assess the prevalence, symptom severity, functional impairment, and treatment of major depressive episode (MDE) in the Iraqi general population. METHODS: The Iraq Mental Health Survey is a nationally representative face-to-face survey of 4,332 non-institutionalized adults aged 18+ interviewed in 2006-2007 as part of the WHO World Mental Health Surveys. Prevalence and correlates of DSM-IV MDE were determined with the WHO Composite International Diagnostic Interview (CIDI). FINDINGS: Lifetime and 12-month prevalence of MDE were 7.4% and 4.0%, respectively. Close to half (46%) of the 12-month MDE cases were severe/very severe. MDE was more common among women and those previously married. Median age of onset was 25.2. Only one-seventh of 12-month MDE cases received treatment despite being associated with very substantial role impairment (on average 70 days out of role in the past year). CONCLUSIONS: MDE is a commonly occurring disorder in the Iraqi general population and is associated with considerable disability and low treatment. Efforts are needed to decrease the barriers to treatment and to educate general medical providers in Iraq about the recognition and treatment of depression.

Hypoglycemic potential of tablet Metformin 500 mg (Glucophage & Metphage): a pharmacological end point evaluation.

Quantitative determination of pharmacological response or clinical end point study is essential for successful evaluation of clinical pharmacology and Bioavailability/ Bioequivalence issues. Stride has been made for proper selection of a quality drug product from the various available therapeutic, which is the prime responsibility of Health care provider and specially pharmacist. Study was conducted in respect to investigate the Pharmacodynamics response, differences and individual variation of oral, Metphage (Metformin 500 mg tablet) as a test formulation manufactured by Efroze Chemical Industries (Pvt.) Ltd. and Glucophage (Metformin 500 mg tablet) as a reference formulation manufactured by Merck Marker. Blood glucose levels/hypoglycemic effect produced by both formulation were studied under cross over trial with respect to placebo/control treatment and result were discussed accordingly. There were no hypoglycemic episodes requiring medical intervention and/or pharmacologic therapy so the patients can easily manage it. Results of the study clearly suggest that formulation manufactured by Efroze Chemical Industries (Pvt.) Ltd. is near to the standard formulation and produced comparable results. No significant differences in pharmacodynamics was observed, however, minor differences might relate with inter individual variation in human volunteers and in different formulation as well as different pharmaceutical unit. Although this data assure the ultimate quality of Metformin 500 mg tablet manufactured by Efroze Chemical Industries (Pvt.) Ltd. but every Generic equivalent should be studied for assurance of safety and efficacy because life of patient is a matter of concern. Such type of study would provide better evaluation of the performance of a drug from a dosage form.

Bioavailability study of tablet Bezafibrate 200 mg (Lipocor).

In order to determine the ultimate quality of any formulated dosage form and rationalize the therapeutic plan as well as to individualize the prescription, in vivo measurement of drug is the modem and specialized expertise of the clinical/research area of pharmacy practice, which provides effectiveness and assures the safety of drugs. All pharmacological, therapeutic or toxic responses are subject to reaching of drug at the site of action through connective tissue. Other than physico chemical properties of drug, there are numerous factors from manufacturing process to biochemical behaviour of the individual which resist in the absorption, distribution, metabolism and elimination of drugs in the biological system. Bezafibrate Tablet 200 mg (Lipocor) an oral conventional formulation manufactured by Efroze Chemical Industries (Pvt.) Ltd. was investigated for bioavailability followed by pharmacokinetic studies on adult, male, healthy, human local population. For this purpose, a sensitive, specific and validated method was used for the estimation of bezafibrate in blood. HPLC was performed on a reversed phase C18 column (flow rate 1.5 ml/min, UV = 230 nm) with 0.02 M buffer of KH2PO4 (Adjusted pH 3.5 with Phosphoric Acid) and Methanol (40: 60) whereas extraction of the drug from the plasma was carried out by deproteinization of plasma according to classical method described in previous studies (Obaid A. et al., 1999). Peak level (Tmax) of Bezafibrate Tablet 200 mg (Lipocor) was observed at about 1.42 +/- 0.53 hours after the dose and practically free Bezafibrate Tablet 200 mg (Lipocor) could be detected in blood after 9 hours. Cmax of the investigated formulation of Lipocor register mark or target was 1732 +/- 374.2 ng/ml. Area under curve (AUC) was 5198.65 +/- 1231.8 ng. hr/ml.

Method development for analysis of gliclazide in human plasma by using high-performance liquid chromatography.

Since 1970, dissolution requirements have been included in tablets and capsules monographs, in general, in response to concerns for bioavailability of equal significance is the recognition of the immense value of dissolution testing as a tool for quality control. Thus, equivalence in dissolution behaviour was sought in the light of both bioavailability and quality control considerations (Coppack et al., 1990). Nonetheless, dissolution profiles are often considered by the industry to ascertain the release rates of drug from tablet formulations as a quality assurance tool. However, in terms of sensitivity, precision and specificity, high-performance liquid chromatographic (HPLC) method may offer additional advantages (Charles & Ravenscroft, 1984 and Nawaz, 2001).

Effect of co administration of haloperidol and large neutral amino acids (tryptophan and valine) on rats striatal dopamine, serotonin and their metabolism.

Haloperidol is a high potency typical neuroleptic used in the treatment of schizophrenia. Administration of haloperidol produces muscles related side effects commonly known as extrapyramidal effects (EPS). These effects are not produced following the administration of atypical neuroleptics such as clozapine. A severe side effect of clozapine treatment is however, agranulocytosis. Development of antipsychotics with little/no EPS and/or other side effects is one of the exploring fields of drug research. This involves investigation on the mechanism by which a typical neuroleptic acting via serotonergic mechanism tends to produce less or no EPS. The present study is, therefore, designed to determine the effect of serotonin precursor tryptophan and a large neutral amino acid (valine) other than tryptophan on the modulation of neurochemical changes in the striatum. Neurochemical estimation were done by HPLC-EC. Present study showed that administration of tryptophan increased tryptophan, 5HT, 5HIAA and DA concentration in the striatum. DOPAC and HVA were not effected. Administration of valine increased DOPAC concentration in the striatum and did not alter tryptophan, 5HT, 5HIAA, DA and HVA concentration. Administration of the haloperidol increased HVA, 5HT and 5HIAA concentration. No effect was produced on tryptophan, DOPAC and DA levels. Valine administration followed by haloperidol injection did not alter striatal tryptophan, 5HT, DA, DOPAC and HVA concentration but decreased 5HIAA concentration. Administration of tryptophan followed by haloperidol injection increased tryptophan and 5HT concentrations and decreased DA levels. No effect was produced on 5HIAA, DOPAC and HVA concentrations. Administration of TRP increased plasma and brain concentration as well as DA levels in the striatum. Administration of valine did not decrease striatal TRP concentration while Haloperidol increased striatal 5-HT and 5-HIAA concentrations and no change in DA levels after haloperidol administration. whereas prior injection of TRP that increased 5HT concentration did not alter haloperidol-induced DA turnover in the brain.