Graves' disease: pathophysiological aspects and considerations about using the chemometric analysis in the study of the disease.

Graves' disease is an immune system disorder that results in the overproduction of thyroid hormones (hyperthyroidism). Thyroid disorders are a societal problem of great public concern because of their high prevalence. This problem can affect the well-being and quality of life of patients. The predisposing factors leading to this disease are not yet fully established and are likely to be interconnected in a complex way. Chemometric analysis allows for the detection of specific relationships between the medical parameter measurements obtained from the patients in an observation group, and the identification of patterns of similarity between these patients. It is not commonly used in clinical trials; however, it can provide reliable information which may help in creating more successful, individualised treatment strategies for established groups (patterns) of patients.The aim of this review is to summarize the latest knowledge about the risk factors for Graves' disease and considerations about using the chemometric analysis in the study of the disease.

Type 2 diabetes mellitus and cardiovascular risk; what the pharmacotherapy can change through the epigenetics.

Diabetes mellitus and cardiovascular diseases are part of the metabolic syndrome and share similar risk factors, including obesity, arterial hypertension, and dyslipidemia. Atherosclerosis and insulin resistance contribute to the development of the diseases, and subclinical inflammation is observed in both conditions. There are many proofs about the connection between epigenetic factors and different diseases, including diabetes and cardiovascular diseases. Interestingly, recent studies show that at least some anti-diabetic drugs, as well as blockers of the renin-angiotensin-aldosterone system (RAAS), exert epigenetic effects aside from their hypoglycemic and antihypertensive functions, respectively. More studies are needed to discover other positive effects of the medications established through epigenetic mechanisms and to find out more about the epigenetic role in the development of diabetes mellitus and cardiovascular diseases.

Recent Developments of Hydrazide/Hydrazone Derivatives and Their Analogs as Anticonvulsant Agents in Animal Models.

Preclinical Research Epilepsy is a chronic devastating neurological disorder characterized by synchronous interictal discharges. Treatment with antiepileptic drugs (AEDs) can alleviate spontaneous seizure activity without preventing the progression and development of epileptogenesis. Current design and development of new AEDs and strategies for the prevention of epilepsy is focused mainly on attenuating uncontrolled seizures, severe side effects and toxicity in chronic drug therapy. It has thus become necessary to discover new chemical pharmacophores with a broad spectrum of activity and less neurotoxicity. Hydrazide/hydrazone derivatives that possess a -CO-NHN=CH- group constitute an important class of compounds for drug development. This review highlights the specific characteristics of various hydrazide/hydrazone derivatives and structurally related semicarbazones, semicarbazides and Schiff base compounds and their anticonvulsant activities. It is focused on the influence of differently substituted pharmacophores developed through SAR studies and testing their activity against different pharmcological targets. Drug Dev Res 77 : 379-392, 2016. © 2016 Wiley Periodicals, Inc.

Differentiation of obese patients at moderate or higher Findrisc score based on their atherogenic index.

OBJECTIVES: The purpose of this study was to reveal different subgroups of patients with at least moderate risk of developing diabetes in the next 10 years, based on clustering of cardiovascular risk factors. METHODS: We performed a one-center cross-sectional study of adult patients (n = 109, median age 45 years) with Findrisc score of above 11 out of 26 maximum. We included in the cluster analysis anthropometrics, lipid and carbohydrate parameters obtained in oral glucose tolerance test (OGTT), insulin, C-peptide, creatinine, C-reactive protein, liver enzymes, beta-cell function, insulin sensitivity and insulin resistance (HOMA calculations). We also evaluated the atherogenic index of plasma (AIP). RESULTS: We identified three metabolic phenotypes of patients with at least moderate Findrisc score-one 'male' (cluster AM, n = 24), and two 'female' phenotypes (cluster AW, n = 9 and cluster BW, n = 76). Men were almost homogenous for their metabolic phenotype, with lower fat percentage than women (p < .05). Most of the women (cluster BW, n = 76) presented with better metabolic pattern i.e. lower insulin resistance, lower C-reactive protein, lower degree of obesity and visceral fat rating (p < .05), despite the higher fat percentage (p < .05). Some of the women, however, (cluster AW, n = 9) presented with parameters very similar to that of men (cluster AM) and significantly higher than in cluster BW. Despite the lack of significant differences in lipid parameters among clusters, AIP was significantly lower in cluster BW (p < .05). CONCLUSION: Most of the women presented with clearly less unfavorable atherogenic risk than men. Two different phenotypes of obese women with at least moderate Findrisc score were revealed, and the level of inflammation seems to be the main discriminant factor. Larger prospective studies are required to elucidate whether those are really two different pathogenically phenotypes or if they belong to the same phenotype's continuum.

The place of inhaled corticosteroids in the treatment of chronic obstructive pulmonary disease: a narrative review.

Inhaled corticosteroids (ICSs) belong to the armament for treatment of chronic obstructive pulmonary disease (COPD) and as such, they are widely used in real life. This is a narrative review on evidence-based papers published in the English language listed in Medline between 1990 and March 2016 discussing ICS application in COPD. Recent meta-analyses clearly show that ICSs are able to decrease the rate of exacerbation and to delay the decline of lung function, although they do not prolong life, nor stop the progression of the disease. ICSs are included in guidelines for COPD treatment, exclusively in combination with bronch-15 odilators. However, adverse effects as pneumonia, cataracts, osteoporosis, etc. seem obvious. Newer studies show that patients with COPD are not a homogeneous population, and recently several phenotypes were identified, including asthma-COPD overlap syndrome (ACOS), among others. The efficacy of ICSs seems to be unequal for different subpopulations of patients with COPD and further research is needed to address a personalized approach in the treatment of COPD patients, and to 20 identify predictors for ICS treatment success. Usage of ICSs in patients with COPD needs to be précised especially in patients with COPD without asthma.

Synthetic cannabimimetics in Bulgaria 2010-2013.

BACKGROUND: The manufacturing, distribution and use of synthetic cannabimimetics (SCs) have seen dynamic changes over the last few years, and have had an unprecedented growth. Forensic toxicologists in Bulgaria faced SCs for the first time in 2010, as compounds detected in seized blends. METHODS: This is a retrospective survey on the SCs seized in Bulgaria 2010-2013. RESULTS: The number of SCs increased progressively: 17 cases in 2010, 38 in 2011, 75 in 2012, and 80 in 2013. In Bulgaria, from 2010 to 2013, there were two cases of toxicologically proved intoxications (with JWH-018). JWH-018 was the most often detected SC in Bulgaria for the whole studied period. The most popular combination detected in 2013 was: UR-144+MAM-2201 with or without STS-135. Highly potent halogenated SCs appeared in 2013. 5F-AКB-48 (nearly 3 kg) was seized in 12 cases. Published data suggest that SCs may have more severe side effects than marijuana. Parallel adaptation of Bulgarian law with adoption of analog laws tried to meet the increased forensic challenges. CONCLUSIONS: Over the last decade, the rapid growth in the number and types of SCs distributed in Europe has challenged the capacity, and sometimes the credibility, of identification, risk assessment and control systems. Forensic toxicology needs to adapt in a timely manner, providing scientific basis of legislative changes.

Effect of zinc on the activity of Cu/Zn superoxide dismutase and lipid profile in Wistar rats.

AIM: The aim of the present study was to analyze the effect of zinc on the activity of Cu/ZnSOD, lipid profile and arterial blood pressure in male Wistar rats. MATERIAL AND METHODS: The study included 53 male Wistar rats with basal weight 190-210 g. The animals were divided into three groups and put on diets with different zinc content. Group I animals (G1, n = 18) were on a diet with zinc content 52 mg/kg, group II animals (G2, n = 18) were on a diet with zinc content 155 mg/kg corresponding to standard food and group III animals (G3, n = 17) received zinc supplementation (236 mg/kg diet). The activity of Cu/ZnSOD was measured in erythrocytes with RANSOD reactive (RANDOX). Zinc content in the laboratory chow and serum concentration of zinc and copper were analyzed by direct flame atomic-absorption spectrophotometry. Lipid profile was determined with reactives of ABX (France). Arterial blood pressure was measured on the rat's tail by an indirect method without anesthesia. RESULTS: Statistically significant decrease (p < 0.05) was found in the activity of Cu/ZnSOD in G1 animals (1993.51 +/- 303.01) compared with G2 animals (2307.07 +/- 240.23). There was a statistically significant increase (p < 0.05) of serum LDL in G3 (1.52 +/- 0.21) compared with G1 animals (1.09 +/- 0.27) and statistically significant increase in the serum triglycerides in G1 animals (1.19 +/- 0.22) compared with G3 animals (0.75 +/- 0.17). CONCLUSIONS: The results indicate that the activity of Cu/ZnSOD changes in relation to zinc diet and this correlates with the change in the arterial blood pressure. Lipid variables also are influenced and zinc supplementation leads to increase in the serum LDL and decrease in the serum triglycerides in Wistar rats.