Further evidence of dopamine transporter dysregulation in ADHD: a controlled PET imaging study using altropane.

BACKGROUND: The dopamine transporter (DAT) is known to be a key regulator of dopamine, and recent studies of genetics, treatment, and imaging have highlighted the role of DAT in attention-deficit/hyperactivity disorder (ADHD). The findings of in vivo neuroimaging of DAT in ADHD have been somewhat discrepant, however. METHOD: Dopamine transporter binding was measured using a highly selective ligand (C-11 altropane) and positron emission tomography (PET). The sample consisted of 47 well-characterized, treatment-na?ve, nonsmoking, non-comorbid adults with and without ADHD. Additionally, control subjects had few symptoms of ADHD. RESULTS: Results showed significantly increased DAT binding in the right caudate in adults with ADHD compared with matched control subjects without this disorder. CONCLUSIONS: These results confirm abnormal DAT binding in the striatum of adults with ADHD and provide further support that dysregulation of DAT may be an important component of the pathophysiology of ADHD.     

Behavior shaping of complete denture patient: a theoretical approach

The psychological status of a geriatric patient undergoing complete denture treatment is one of the key determinants of the success of prosthesis. Hence, the understanding and behavior management of such patients is of paramount importance for any clinician aspiring to be a successful in practice. Even though several attempts have been made to understand the effects of psychology of patients undergoing this particular treatment on the final outcome of treatment, no single theory or classification has been proposed so far as to be able to completely understand the thought process of geriatric patients. The aim of this paper is to propose a theoretical approach, a step by step guide to clinicians to better understand the thoughts, aspirations and expectations of complete denture patients and their effects and consequences in different patients, when not met with.     

Ameliorating effect of coenzyme Q10, riboflavin and niacin in tamoxifen-treated postmenopausal breast cancer patients with special reference to lipids and lipoproteins

OBJECTIVES: Tamoxifen (TAM), a non-steroidal anti-estrogen that is widely used in adjuvant therapy for all stages of breast carcinomas and in chemoprevention of high-risk group. The hepatic estrogenic effect of TAM induces hypertriglyceridemia by reduced activity of lipolytic enzymes (LPL) on triglycerides. Coenzyme Q10 (Co Q10), riboflavin and niacin are proved to be potent antioxidant and protective agents against many diseases including cancer and cardiovascular diseases (CVD). In this context, the objective of the study is to find the effect of the combined modality of Co Q10 (100 mg), riboflavin (10 mg) and niacin (50 mg) with TAM (10 mg twice a day) on serum lipids and lipoprotein levels in postmenopausal women with breast cancer. DESIGN AND METHODS: The vitamin supplementation with tamoxifen was given for a period of 90 days. Blood samples were collected at the base line, 45th and 90th day during the course of treatment. Plasma total cholesterol (TC), free cholesterol (FC), ester cholesterol (EC), phospholipids (PL), triglycerides (TGL), free fatty acids (FFA), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and very low density cholesterol (VLDL-C) were estimated in 78 untreated, only TAM-treated and combinatorialy treated group along with 46 age- and sex-matched controls. RESULTS: Serum TGL and VLDL-C (p<0.001) were found to be significantly elevated and LDL-C (p<0.01), significantly reduced among TAM-treated patients as compared to the untreated breast cancer subjects. All the lipids and lipoprotein levels were found to be significantly altered in the untreated breast cancer patients when compared to their normal counterparts. All the lipid and lipoprotein abnormalities were reverted back to near normal levels on 90 days of treatment on combinatorial therapy. CONCLUSION: The study figures the altered lipid and lipoprotein levels in the untreated and TAM-treated breast cancer patients. On combination therapy with Co Q10, riboflavin and niacin, it counteracts the tamoxifen-induced hyperlipidemia to normal levels.     

Structural requirements for imidazo[1,2-a]pyrazine derivatives as Aurora A kinase inhibitors and validation of the model

Aurora kinases belong to the family of serine/threonine kinases. They are divided into three subclasses, Aurora A kinase, Aurora B kinase, and Aurora C kinase and are reported to be vital for cell proliferation. Abnormal expression of these enzymes leads to cancer. Predictive CoMFA and CoMSIA based quantitative structure activity relationship models have been developed on 51 imidazo[1,2-a]pyrazine derivatives reported previously by Merck Research Laboratories. AutoDock was used for docking of the most active compound (34) and the conformation thus obtained was used for the alignment of 3D structures. The developed (CoMSIA-SEHD) model showed good predictive ability with predictive squared correlation coefficient (r ²) value of 0.752. The best model was validated systematically using different validation parameters. The CoMSIA model gave useful information to understand features required to modify and develop new potential Aurora kinase inhibitors.     

Pharmacological control of blood sugar

Diabetes is a chronic and progressive metabolic disorder characterized by hyperglycaemia. The two main types of diabetes are type 1 diabetes (T1DM) where there is complete lack of insulin and type 2 diabetes (T2DM) which may be due to a combination of insulin resistance and relative insulin deficiency due to impaired β-cell function. Good control of blood glucose near physiological limits is vital to reduce long-term microvascular and macrovascular complications of diabetes. Insulin replacement is a life-saving measure in individuals with T1DM whereas the mainstay of therapy in T2DM includes oral agents, non-insulin injectables (incretin mimetics) and insulin. In T2DM, the incretin mimetics have revolutionized recent treatment options by reducing blood glucose, promoting weight loss and improving β-cell function. Moreover, the emergence of a new class of drugs such as the sodium–glucose transporter inhibitors for patients with T2DM holds much promise. Despite the availability of several drugs to treat this chronic debilitating condition, the management of hyperglycaemia remains challenging. The role of diet, lifestyle changes and patient education is of paramount importance and should be pursued aggressively. This review will look at drugs currently used to optimize blood glucose control and briefly discuss the role of newer therapeutic agents.     

Substituted aminoalcohol ester analogs of indomethacin with reduced toxic effects

Synthesis and evaluation of five different N,N-disubstituted aminoethanol ester derivatives of indomethacin bearing structural resemblance to the aminoethanol ester class of anticholinergics are reported herein. The anticholinergic activity was incorporated into the intact esters to overcome the gastric toxicity of indomethacin, not only by blocking the acidic functionality but also by decreasing gastric secretions and motility. These derivatives exhibited in vitro stability in buffers of pH 2.0 and 7.4 for 6 h and were readily hydrolyzed by human plasma esterases to liberate the parent drug. All the derivatives were significantly less irritating to the gastric mucosa than the parent drug. Though only two esters showed antiinflammatory activity similar to that of the parent drug at equivalent dose levels, all the esters were equipotent to indomethacin in the mouse acetic acid–induced writhing assay for analgesic action. The present evaluation indicates that the combined pharmacological properties of these ester derivatives may prove useful for design and development of novel gastric sparing antiinflammatory molecules with potentially important therapeutic applications.     

Moderate visual impairment in India: the Andhra Pradesh Eye Disease Study

AIM: To assess the prevalence and demographic associations of moderate visual impairment in the population of the southern Indian state of Andhra Pradesh. METHODS: From 94 clusters in one urban and three rural areas of Andhra Pradesh, 11 786 people of all ages were sampled using a stratified, random, cluster, systematic sampling strategy. The eligible people were invited for interview and detailed dilated eye examination by trained professionals. Moderate visual impairment was defined as presenting distance visual acuity less than 6/18 to 6/60 or equivalent visual field loss in the better eye. RESULTS: Of those sampled, 10,293 (87.3%) people participated in the study. In addition to the previously reported 1.84% prevalence of blindness (presenting distance visual acuity less than 6/60 or central visual field less than 20 degrees in the better eye) in this sample, 1237 people had moderate visual impairment, an adjusted prevalence of 8.09% (95% CI 6.89 to 9.30%). The majority of this moderate visual impairment was caused by refractive error (45.8%) and cataract (39.9%). Increasing age, female sex, decreasing socioeconomic status, and rural area of residence had significantly higher odds of being associated with moderate visual impairment. CONCLUSIONS: These data suggest that there is a significant burden of moderate visual impairment in this population in addition to blindness. Extrapolation of these data to the population of India suggests that there were 82 million people with moderate visual impairment in the year 2000, and this number is likely to be 139 million by the year 2020 if the current trend continues. This impending large burden of moderate visual impairment, the majority of which is due to the relatively easily treatable refractive error and cataract, would have to be taken into account while estimating the eye care needs in India, in addition to dealing with blindness. Specific strategies targeting the elderly population, people with low socioeconomic status, those living in the rural areas, and females would have to be implemented in the long term to reduce moderate visual impairment.