A comprehensive review on the role of dopamine in the pathophysiology of tardive dyskinesia

Tardive dyskinesia (TD) is a neurological syndrome characterized by involuntary, repetitive, and unusual movements that primarily impact the orofacial region while also extending to other body parts, encompassing chorea, dystonia, tics, buccolingual stereotypy, and akathisia. This condition stems from iatrogenic factors, particularly the chronic administration of medications that obstruct dopamine receptors. Predominantly implicated are antipsychotic drugs, utilized primarily for schizophrenia and bipolar disorder treatment. These drugs modulate dopamine levels, yet prolonged usage can induce alterations in dopamine receptor sensitivity and disruptions in dopaminergic pathways, consequently fostering TD. Dopamine, a pivotal neurotransmitter governing motor control, motivation, reward processing, and emotional regulation, exerts its effects through distinct dopamine receptor types, of which the D2 subtype assumes particular significance in TD development. The persistent blockade of D2 receptors by antipsychotics prompts a compensatory surge in receptor numbers and sensitivity, ultimately contributing to TD's emergence. In essence, TD reflects a complex interplay between medical intervention and neurological intricacies. The protracted influence of antipsychotics on dopamine receptors highlights the delicate equilibrium essential for optimal brain function. The unconventional movements characterizing TD underscore the intricate role of dopamine and its receptors in orchestrating neural equilibrium.

Estradiol and lipid levels in men with acute myocardial infarction

Background: The incidence of myocardial infarction (MI) is more common in men when compared with women and women after menopause are at high risk of MI. This gender difference in CVD risk might be because of the difference in the circulating estrogen levels in men and women. Dyslipidemia is also one of the major causes of MI. The present study was aimed to estimate the levels of serum estradiol and serum lipids in newly diagnosed male MI cases and to find out any correlation between these two.Methods: The study was conducted on 50 newly diagnosed MI admitted in Cardiology department Narayana general hospital and Medical College, Nellore. Only males were included in the study. Fifty age and sex-matched healthy individuals were selected as controls. Lipid levels are estimated by endpoint colorimetric assay (HUMANSTAR kit) and estradiol was estimated by Chemiluminance immune assay (CLIA).Results: Significantly raised levels of estradiol (p-value <0.0001) and low HDL cholesterol (p-value =0.0085) levels were noticed among the cases compared to controls. No significant correlation was observed between estradiol and lipoproteins (HDL and LDL).Conclusions: The results of the present study in acute MI compared to controls show hyper estrogenemia in Male MI cases, which may be the underlying cause for thrombosis in acute MI. Decreased levels of HDL cholesterol are observed in the MI cases which are known to increase the risk of Atherosclerosis. No significant correlation were noticed between Estradiol and HDL cholesterol in men with acute MI.

Alterations of serum high sensitive C reactive protein and lipid levels in newly diagnosed myocardial infarction subjects

Background: Acute Myocardial Infarction (AMI) is one of the major causes of mortality in the world. Atherosclerosis leading to AMI is the most common and severe clinical manifestation observed. Dyslipidemia is one of main traditional risk factor for MI, but in more than 50% of CHD events dyslipidemia was absent.  Atherosclerosis is considered as both a chronic inflammatory condition and a disorder of lipid metabolism. The present study was aimed to estimate the levels of serum lipids (total cholesterol, LDL cholesterol, HDL cholesterol) and hs-CRP an inflammatory marker in newly diagnosed AMI cases and to find out any correlation between these two.Methods: The study was conducted on 50 newly diagnosed myocardial infarction cases, admitted in Cardiology Department Narayana Medical College, Nellore. Both the sexes were included. Fifty age and sex matched healthy individuals were selected as controls. Lipid levels are estimated by end point colorimetric assay (HUMANSTAR kit) and hs-CRP was estimated by immunofluorescence technique (Boditechkit).Results: Significant raised levels of hs-CRP (p value <0.0001) and low HDL cholesterol (p value =0.0085) levels among the cases was noticed. A significant positive correlation was observed between LDL cholesterol and hsCRP (r=0.109, p=0.040). A non-significant positive correlation between hsCRP and HDL cholesterol  (r=0.291, p=0.453) was observed.Conclusions: The results of the study implicate the role of inflammatory component in causing atherosclerosis or coronary artery disease rather than dyslipidaemias alone to be attributed for atherogenesis. Concomitantly HDL cholesterol levels were found to be low in cases that results from the inflammatory component in atherogenesis.

Hyperuricemia is a risk factor for cardiovascular risk?

Background: Uric acid is the end product of purine metabolism in humans degraded by the hepatic enzyme, urate oxidase (uricase), to allantoin, which is freely excreted in the urine. However, during the Miocene epoch (20 to 5 million years ago), 2 parallel but distinct mutations occurred in early hominoids that rendered the uricase gene non-functional. Uric acid (UA) is a known endogenous scavenger, which provides a major part of the antioxidant capacity against oxidative and radical injury.Methods: The present study was conducted over a period of one year on outpatients attending the General Medicine Department at Narayana General Hospital, Nellore. The study was included 998 subjects (500 male and 498 female) and authors excluded other complications. Data were analyzed by SPSS software.Results: Serum uric acid of the subjects were measured. The mean and standard deviation were calculated for all the Biochemical parameter. The significance between the groups was determined using Student t-test for equality of means. The two-tailed P value is less than 0.0001, which is statistically significant. Confidence interval: the hypothetical mean is 1.0000 and the actual mean is 6.4600. The difference between these two values is 5.4600. The 95% confidence interval of this difference from 5.3489 to 5.5711. Intermediate values used in calculations; t = 96.4583, df = 999 and standard error of difference p = 0.057.Conclusions: About 53% of the subjects of the study are hyperuricemia, with about 74% of these subjects (or about 39% of the total) diagnosed with hypertension or diabetes mellitus or both, indicating a high CVD risk.

A comparative study of trace element levels in coronary artery tissue of Coronary heart disease patients with serum levels in healthy individuals.

Background: Cardiovascular disease/Coronary artery disease (CAD), leading cause of global morbidity and mortality covers any disease of the circulatory system. In -vivo antioxidant nutrients which include vitamin C, trace elements such as Se, Zn and Cu play a crucial role in defending against oxidant damage. Objective: The aim of the present study was to investigate the changes occurring in the levels zinc (Zn), copper (Cu), and Selenium (Se) in coronary artery tissues of patients with CAD. Material and methods: Coronary artery samples collected from these patients during bypass surgery from known CAD patients. These samples were analyzed for Se, Zn, and Cu; results are expressed in terms of wet weight. Normal Healthy serum Se, Zn, and Cu levels were also analyzed to compare with coronary artery samples. Results: The levels of Zn, Cu and Se in patient’s coronary artery samples were observed to be very low when compare to Zn, Cu and Se levels of healthy person’s serum samples. In addition, our study showed that the levels of Zn and Cu in coronary artery samples were low when they compared to heart tissue Zn and Cu levels from CVD patients from other studies. Whereas, Se levels in coronary artery samples in our study are same as heart tissues samples in previous other studies. Yet, there was limited/no observational studies were published to identify levels of trace element levels in coronary artery samples. Hence our present observations interpreted the levels of Zn, Cu and Se in coronary artery samples with 20 numbers of sample size only; further, higher number of samples needed to formulate the standard reference ranges of these trace elements in setting up a newer biochemical marker in correlation/interpretation of CVD/CAD. Conclusion: The finding of our results showed that Se levels in coronary artery observed to be same as heart tissue levels from other study. The myocardial clinical manifestation seems to be due to alteration of levels of these trace elements in serum, tissue levels in patients. In our studies, however, the patients with coronary heart disease had,in general, lower concentrations of Zinc,copper in serum than the healthy controls.

Correction of Serum Leptin after Successful Kidney Transplantation.

Introduction: Serum leptin levels are increased in chronic kidney disease (CKD) patients primarily due to decreased clearance by kidneys. As leptin is a 16 Kda protein, it is also not cleared even by dialysis using conventional dialyzers or by continuous ambulatory peritoneal dialysis (CAPD). Studies have shown that elevated leptin levels are corrected after successful renal transplantation. With this intention, we determined if restoration of renal function with kidney transplantation can reduce serum leptin concentration in CKD patients. Materials and Methods: A total of 21 Patients undergoing living donor kidney transplantation were studied. There were 13 men and 8 women, from 16 to 45 years of age. All patients were receiving Hemodialysis prior to transplant. All patients received triple immunosuppressant therapy after the surgery. There were no graft rejections. Blood samples were collected under fasting conditions before and 6 days after transplantation. Results: The mean age of the patients was 28.38±9.38 years. Pre transplantation leptin concentration was 9.96 + 3.48 ng/ml and this decreased to 4.07±1.7 ng/ml within six days of transplantation (p<0.0001). However there was no concomitant change in Body Mass Index (BMI) as the follow-up was too short. Plasma Creatinine level declined from 7.5±1.6 mg/dl to 1.1±0.7 mg/dl within six days after transplantation. Conclusion: Successful renal transplantation immediately reduces serum leptin levels along with serum creatinine. The reduction in serum leptin levels after renal transplantation is likely due to reversal of renal function. Neither pre nor post transplant plasma Leptin levels correlated significantly with BMI in our study.

Vanadium supplementation reduces high fat diet induced hyperlipidemia, hyper insulinemia & hyperglycemia in rabbits.

Vanadium is considered as an essential trace element in some animals. In human’s classification of vanadium as an essential nutrient is still a topic of debate among various research groups. Nutritionally vanadium is thought to be a cofactor in various enzymatic reactions. Increased levels of insulin in blood (hyperinsulinemia) associated with type-2 diabetes mellitus. Increase intake of fat induces hyperinsulinemia which may leads development of type-2 diabetes mellitus. The present study aimed to know the effect of vanadium supplementation on high fat diet induced hyperlipidemia, hyperinsulinemia and hyperglycemia. In this study New Zealand white breed male rabbits divided into three groups. Group-I: rabbits fed with standard diet Group-II: fed with group-I diet and egg yolk, Group-III: rabbits fed with group-II diet and supplemented with 0.5mg/kg of elemental vanadium as sodium meta vanadate. Total cholesterol, LDL-cholesterol and Triglycerides were significantly decreased in G-III when compared to G-II after the experiment. HDL-cholesterol levels are similar in G-II & G-III. Plasma glucose and insulin levels were significantly decreases in G-III than G-II. The present study shows the antidiabetic and antilipidemic role of vanadium in the experimental rabbits. Supplementation of vanadium may prevents hyperglycemia and cardiovascular risk factors like, insulin resistance and hyperlipidemia in diabetes mellitus.

Tumor necrosis factor–alpha in the development of insulin resistance in type 2 diabetes mellitus.

Obesity and Insulin resistance are very frequent disorders and are described as the dominant risk factors for cardiovascular diseases. Recent research suggests that TNF-alpha, an adipocytokine plays a key role in the development of insulin resistance. Aim of the study was to estimate TNF-alpha levels and to investigate the association of TNF-alpha with the various factors associated with insulin resistance like Body mass index, Waist Hip Ratio, fasting insulin etc. A total of 100 subjects attending out patient department of General Medicine , Narayana Medical College , Nellore were selected for the study.50 patients were diagnosed as type-2 diabetics and 50 subjects were taken as normal healthy controls who attended for a general check-up. Anthropometric and biochemical measurements were analyzed. Serum Insulin and TNF-α were measured using chemiluminescence method and ELISA method respectively. Homeostasis model assessment score was used to gauge the level of insulin resistance. Our Results showed significant elevation in TNF-alpha levels in diabetic subjects and correlations between TNFalpha Body Mass Index and HOMAIR were significant. All correlations were stronger for females compared to males.

Imbalance of oxidants and antioxidant systems in subjects with cirrhosis.

Oxidative stress has been increasingly implicated in the pathogenesis of cirrhosis. Ethanol and various viral infections will increase the production of reactive oxygen species (ROS) in the liver, resulting in an imbalance between oxidants and antioxidants. Thus determination of oxidants along with antioxidants,stated the role of oxidative stress more accurately in the pathogenesis of liver cirrhosis. In the present study we measured the markers of prooxidants, erythrocyte malondialdehyde (MAD), antioxidants that included erythrocyte catalase, reduced glutathione (GSH), glutathione peroxidase (GPx). 30 subjects with age 25-60 years, who were diagnosed as having liver cirrhosis by the department of Gastroenterology, Narayana Medical Hospital were included, 30 normal healthy individuals of the same age were selected as control . The results clearly indicated that the levels of pro oxidants, MDA were high in cirrhotic subjects than in the controls with p value of 0.0001. The levels of antioxidant enzymes GSH, Catalase were low in cirrhosis with p value of 0.0001 (GSH) and 0.067(Catalase). But the mean value of glutathione peroxidase was high in cirrhosis than in controls. This may be due to conterregulation with oxidative stress. Hence this study indicates the role of oxidative stress in liver cirrhosis and it clearly defines the imbalance between oxidants & antioxidants.

Association of insulin resistance with redox imbalance in patients with non diabetic hypertension.

Oxidative stress involved in the pathogenesis of several diseases. Hypertension itself acts as source of oxidative stress. Insulin resistance is involved in the pathogenesis of essential hypertension. In the present study an attempt was made to study the association between insulin resistance and oxidative stress in non diabetic hypertensive patients. Two hundred and three, non diabetic hypertensive patients and two hundred and ten, healthy normotensive subjects were enrolled in this study. Malondialdehyde, reduced glutathione, glutathione peroxidase, Fasting insulin and HOMA-IR levels were estimated in both groups. Fasting insulin, reduced glutathione, glutathione peroxidase and MDA shows significant difference between cases and controls. Among the patients HOMA-IR were significantly correlated with lipid peroxides and shows negative correlation between HOMAIR and glutathione peroxidase. Increased HOMA-IR was found in non diabetic hypertensive patients. This study reveals the link between oxidative stress and insulin resistance.

Inhibition of angiotensin converting enzyme activity by reduced glutathione: A dose dependent invitro study.

The Angiotensin converting enzyme (ACE) is a dipeptidyl carboxypeptidase and plays an important role in the regulation of blood pressure. Several potent inhibitors of this enzyme have been reported to be active antihypertensive agents. Sulfhydryl (SH) group containing ACE inhibitors used as a antihypertensive agents. Reduced glutathione (GSH) as antioxidant play an important role in reducing the blood pressure. Several recent studies have shown that reduced glutathione enhance nitric oxide pathway and increases the bioavailability of nitric oxide resulting in vasodilatation. In this study reduced glutathione and oxidized glutathione (GS-SG) were investigated for inhibition against ACE using Hip-His-Leu (HHL) as substrate. The inhibition of ACE by different concentrations of reduced glutathione was much more than that of oxidized glutathione. The inhibition of ACE by reduced glutathione ranges from 12.5% to 60%. Oxidized glutathione shows less than 5% of inhibition. This study shows that apart from the antioxidant role, reduced glutathione inhibits ACE activity which plays a crucial role in the regulation of blood pressure.

Auto antibodies against oxidized low density lipoproteins and lipid peroxidation in patients with essential hypertension

Lipid peroxidation has been suggested to play a key role in the oxidative modification of LDL (oxd-LDL) which stimulate the production of auto antibodies by Bcells and anti-oxd LDL antibodies are produced. These antibodies could represent a biological marker of oxidative stress and serve as markers of atherosclerosis. Essential hypertension is a major risk factor for atherosclerosis, recently border line hypertension also has been shown to be a risk factor for atherosclerosis. The aim of this study is to examine the correlation between oxd -LDL antibodies and lipid peroxidation in patient with essential hypertension. Blood samples were collected from patients with essential hypertension (n=155) and healthy individuals (n=160) levels of Malonaldihyde (MDA), Total cholesterol, Triglycerides, HDL and LDL were estimated by spectrophotometry and levels of Oxd- LDL antibodies were obtained by ELISA. Plasma levels of MDA, anti-oxdLDL antibodies, Total cholesterol and LDL Cholesterol is higher in patients than those in controls. Among patients concentration of MDA, total cholesterol and LDL cholesterol were not significantly different, however the concentration of anti-oxd LDL were higher in essential hypertensive patients (p=0.003). Significant positive correlation was observed between plasma levels of MDA, total cholesterol, LDL cholesterol and the concentration of anti-oxdLDL in patients but not in the controls. In conclusion High concentrations of anti-oxdLDL and MDA suggest an increase in oxidative stress that would contribute to the development of atherosclerosis. The observed correlation of MDA with anti-oxdLDL indicates the relationship between free radicals and atherosclerosis in essential hypertension.

Effect of Pseudomonas aeruginosa on the giant freshwater prawn, Macrobrachium rosenbergii--histopathological and electron microscopic study.

The giant freshwater prawn Macrobrachium rosenbergii was injected with an inoculum containing LD, 96 hr dose of 10' Pseudomonas aeruginosa (MTCC 1688) to determine the histopathological effects in vivo. The comparison of tissues of both the control and the bacterial endotoxin treated prawns after 96 hr revealed significant degenerative changes in treated prawns. Both light microscopic and electron microscopic observations revealed the infiltration of the tissues of Pseudomonas sp in the muscular and hepatopancreatic tissues of prawn. The muscular tissue changes in the myofibrillar arrangement with blockage at the gap junctions and necrotic lesions were observed. The hepatopancreatic cells were vacuolated with hypertrophied nucleus. Atrophy of hepatopancreatic tubules was conspicuous. The pathogenicity of Pseudomonas aeruginosa is attributed to its infiltration and multiplication inside the tissues and the consequent release of extra-cellular enzymes for its metabolism. The degeneration of host tissues is also attributed to the latter.

Freshwater lakes--a potential source for aquaculture activities--a model study on Perumal Lake, Cuddalore, Tamil Nadu.

The freshwater Perumal lake located at Cuddalore was assessed for its suitability and potential for aquaculture practices. Various hydrobiological parameters determined reveals that the various physicochemical characteristics are with in normal range of values. The DO level, BOD and COD values determined in the lake revealed the consequences of community activities and pollution possibilities. The primary productivity data revealed maximum productivity during March which infer that the lake is unaffected by anthropogenic disturbance and community contamination. The bacterial count remained higher during the monsoon periods, which characterize profuse rainfall and storm water discharge into the lake. The microfauna includes zooplankter such as cladocerans, copepods, rotifers and ostracods. Benthos include carps, catfishes, mullets and prawns. The above study revealed that the various parameters in the lake conform to the levels suited for freshwater fish culture and represents a resource for scientific management.

Ascorbic acid levels in the proglottides of cestode parasite Avitellina lahorea (Woodland, 1972) and host serum (sheep) in relation to their sexual maturity.

The ascorbic acid level was highest in immature proglottides and lowest in gravid proglottides of Avitellina lahorea, the gut parasite of sheep. The ascorbic acid content in all the regions of the parasite viz., immature, mature and gravid taken together remained higher to the value of the host serum. The above gradient between the parasite and the host serum interface suggested its active uptake on the part of the parasite.

Cutaneous manifestations in patients with chronic renal failure on hemodialysis.

BACKGROUND: Chronic renal failure (CRF) presents with an array of cutaneous manifestations. Newer changes are being described since the advent of hemodialysis, which prolongs the life expectancy, giving time for these changes to manifest. AIM: The aim of this study was to evaluate the prevalence of dermatologic problems among patients with chronic renal failure (CRF) undergoing hemodialysis. METHODS: One hundred patients with CRF on hemodialysis were examined for cutaneous changes. RESULTS: Eighty-two per cent patients complained of some skin problem. However, on examination, all patients had at least one skin lesion attributable to CRF. The most prevalent finding was xerosis (79%), followed by pallor (60%), pruritus (53%) and cutaneous pigmentation (43%). Other cutaneous manifestations included Kyrle's disease (21%); fungal (30%), bacterial (13%) and viral (12%) infections; uremic frost (3%); purpura (9%); gynecomastia (1%); and dermatitis (2%). The nail changes included half and half nail (21%), koilonychia (18%), onychomycosis (19%), subungual hyperkeratosis (12%), onycholysis (10%), splinter hemorrhages (5%), Mees' lines (7%), Muehrcke's lines (5%) and Beau's lines (2%). Hair changes included sparse body hair (30%), sparse scalp hair (11%) and brittle and lusterless hair (16%). Oral changes included macroglossia with teeth markings (35%), xerostomia (31%), ulcerative stomatitis (29%), angular cheilitis (12%) and uremic breath (8%). Some rare manifestations of CRF like uremic frost, gynecomastia and pseudo-Kaposi's sarcoma were also observed. CONCLUSIONS: CRF is associated with a complex array of cutaneous manifestations caused either by the disease or by treatment. The commonest are xerosis and pruritus and the early recognition of cutaneous signs can relieve suffering and decrease morbidity.

Influence of Vibrio parahaemolyticus MTCC 451 on the levels of ascorbic acid and histamine in Penaeus monodon (Fabricius).

Juvenile shrimps (Penaeus monodon) weighing about 15-20 gms were procured from the grow-out ponds and reared under laboratory conditions. They were challenged with Vibrio parahaemolyticus MTCC 451 and their LD50 value was evaluated. The ascorbic acid and the histamine activity of both the control and experimental groups were assessed. The results showed a marked decline in both the parameters at all intervals. This reveals the pathogenesis of the inoculated bacterial strain, which affects the defense mechanism by reducing the glutathione content by the decreased level of ascorbic acid and letharginess by the decreased histamine content of the experimental prawns.

Enumeration of hydro-biological parameters and assessment of eco-aquafarming potential in the Velachery Lake (Chennai).

In recent years, aquaculture has acquired vast potential in providing livelihood, security as well as fulfilling the nutritional requirements of the growing population. The hydro-biological parameters studied in Velachery Lake revealed that a large number of essential parameters are conforming to the levels suggested for a shrimp farm. The abundance and availability of zooplankton population reveal their importance in prawn culture.

Effect of Pseudomonas aeruginosa (MTCC 1688) on the tissue phosphatases activity on Macrobrachium rosenbergii (De Man).

A time course study on the endotoxin toxicity of the gram negative bacteria, Pseudomonas aeruginosa MTCC 1688 on the tissue phosphatases activity on the giant freshwater prawn, Macrobrachium rosenbergii was conducted. The results revealed marked elevation of both acid and alkaline phosphatase activity in the haemolymph and body muscle. The hepatopancreas showed reduced phosphatase activity compared to control. The enzymes, being non-specific in action and particularly the acid phosphatase being of lysosomal origin, their increase in muscle and haemolymph has pathogenic significance in the inoculum treated prawns.

Copper sulphate (CuSO4) toxicity on tissue phosphatases activity and carbohydrates turnover in Achatina fulica.

A time course study on the sublethal toxicity of CuSO4 on tissue carbohydrate metabolites level and their phosphatases activity in Achatina fulica revealed differential response. The levels of total carbohydrates and glycogen in the body mass muscle, foot muscle and hemolymph revealed their involvement in the endogenous derivation of energy during stress. The same metabolites in digestive gland revealed its importance to reproduction and development. The lactate accumulated in all the tissues implied the mechanism of CuSO4 toxicosis in the metabolic acidosis. The decrease of pyruvate in foot muscle, body mass muscle and hemolymph inferred the preponderance of glycolysis in energy derivation. In contrast, the pyruvate concentration in digestive gland revealed its differential response in the stress metabolic sequence of changes, as a unique tissue. The lactate/pyruvate ratio and the calcium content in tissues constitute direct evidences for the snails adaptation to toxic stress.