Effects of atorvastatin on talinolol absorption: A potential drug-drug interaction.

In this study, we aimed to determine the drug-drug interaction potential between atorvastatin (ATOR), and talinolol (TAL). Concentration-dependent effects of ATOR on the intestinal permeability of TAL were investigated by an in situ intestinal perfusion method. Dose-dependent effects of ATOR on TAL exposure were evaluated by measuring plasma concentrations after oral administration in rats. ATOR slightly changed the intestinal secretion of TAL in jejunum but not in colon. Plasma AUC levels of TAL were elevated by co-administration of ATOR at low and high doses whereas medium doses of ATOR resulted in a decrease in TAL bioavailability. However, these changes were not statistically significant. In our study, the pharmacokinetics of TAL were not affected by the concurrent use of ATOR in rats. In conclusion, it should be considered that complex interplay between the efflux and uptake transporters in the tissues and inhibition of these transporters by modulating agents may overshadow individual effects of each other.

Prevalence and significance of MEFV gene mutations in patients with sarcoidosis.

OBJECTIVES: Sarcoidosis is a chronic granulomatous disease. Pyrin has anti-inflammatory activity in the regulation of inflammasomes and is encoded by the Mediterranean fever (MEFV) gene. MEFV gene mutations trigger the inflammatory cascade and cause familial Mediterranean fever (FMF). A relationship between various rheumatic diseases and MEFV gene mutations has been demonstrated. The aim of this study was to determine the prevalence of the MEFV gene mutation in Turkish patients with sarcoidosis and to detect any possible correlation with disease phenotype. METHOD: The study included 78 sarcoidosis patients and 85 healthy subjects matched for age, gender, and ethnicity. MEFV gene mutations were investigated with the FMF strip assay, which is based on reverse hybridization of biotinylated polymerase chain reaction (PCR) products. RESULTS: Of the 78 patients with sarcoidosis, nine (11.5%) were found to be carriers of MEFV gene mutations. The distribution of these nine mutations were: three (3.8%) V726A, two (2.5%) E148Q, two (2.5%) M680I, one (1.3%) A744S, and one (1.3%) K695R. Carriers of M694V, M694I, R761H, and P369S were not detected in any of the sarcoidosis patients. None of the sarcoidosis patients were found to be compound heterozygous carriers. The prevalence of the MEFV gene mutation carrier detected in the healthy control group was 22.4%. The distribution of the 19 MEFV gene mutations found in the healthy controls was: nine (10.6%) E148Q, two (2.3%) M694V, one (1.2%) M694I, one (1.2%) M680I, two (2.3%) V726A, one (1.2%) A744S, two (2.3%) K695R, and one (1.2%) P369S. When compared with the control group, a lower prevalence of the MEFV gene mutation carrier was found in sarcoidosis patients but this was not statistically significant (p = 0.067). In nine patients found to be MEFV gene mutation carriers, higher serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels and higher numbers patients with arthritis, enthesitis, and ankle arthritis were found (p = 0.01, p = 0.04, p = 0.028, p = 0.05, p = 0.05, respectively). CONCLUSIONS: When we compared Turkish sarcoidosis patients with the healthy control group, we found a lower prevalence of MEFV gene mutations. In sarcoidosis patients, the MEFV gene mutation carrier was found to be related to high acute-phase responses, arthritis, and enthesitis. The existence of MEFV gene mutations may have a preventive role with regard to the development of sarcoidosis. Prospective studies that include larger patient populations are needed.

Extending the Lincoln-Petersen estimator for multiple identifications in one source.

The Lincoln-Petersen estimator is one of the most popular estimators used in capture-recapture studies. It was developed for a sampling situation in which two sources independently identify members of a target population. For each of the two sources, it is determined if a unit of the target population is identified or not. This leads to a 2 × 2 table with frequencies f11 ,f10 ,f01 ,f00 indicating the number of units identified by both sources, by the first but not the second source, by the second but not the first source and not identified by any of the two sources, respectively. However, f00 is unobserved so that the 2 × 2 table is incomplete and the Lincoln-Petersen estimator provides an estimate for f00 . In this paper, we consider a generalization of this situation for which one source provides not only a binary identification outcome but also a count outcome of how many times a unit has been identified. Using a truncated Poisson count model, truncating multiple identifications larger than two, we propose a maximum likelihood estimator of the Poisson parameter and, ultimately, of the population size. This estimator shows benefits, in comparison with Lincoln-Petersen's, in terms of bias and efficiency. It is possible to test the homogeneity assumption that is not testable in the Lincoln-Petersen framework. The approach is applied to surveillance data on syphilis from Izmir, Turkey.

Association of uric acid and carotid artery disease in patients with ischemic stroke.

BACKGROUND AND PURPOSE: Some previous studies reported an independent association between uric acid and coronary artery disease, while little is known on the association among uric acid and carotid artery disease (CAD). To address this issue, we investigated the association between CAD and higher uric acid level because of the well-known importance of the carotid artery pathologies for ischemic stroke. METHODS: Between 2009 and 2012, we conducted a study among 406 consecutive first-ever ischemic stroke patients to assess the relationship between uric acid and carotid artery. A mean intima-media thickness IMT was calculated for the wall of the left and right common carotid arteries (CCA) and IMT of the bifurcation of the carotid arteries. CAD was assessed by neuroimaging techniques in patients with carotid artery stenosis more than 50%. Logistic regression models were used to determine the relation among pathological changes of the carotid artery and higher uric acid level. RESULTS: In patients with hyperuricemia, the frequency of age (>60 years), hypertriglyceridemia, higher apo B, renal failure were significantly higher than those with normal uric acid level. CAD was more frequent in patients with hyperuricemia than those with normal uric acid level (OR, 1.8, 95% CI, 1.1-3.1; P = 0.01). In patients with higher uric acid level, the mean of the IMT of the CCA and of the bifurcation of the carotid artery were higher than those with normal uric acid level (P = 0.001 for each). Covariance matrix analysis displayed a strong correlation between CAD and age (>60 years) (P < 0.05), sex (P < 0.01), hyperuricemia (P < 0.01), hypertension (P < 0.05), and hypercholesterolemia (P < 0.05). In the models of regression analysis, a strong association was found among patients with CAD and sex, renal failure, hyperuricemia, number of plaques, and size of plaques. CONCLUSION: Our study demonstrated that higher uric acid level is strongly associated with CAD. Elevated uric acid might be injurious for large cerebral arteries with some probable confounding risk factors. Further prospective large clinical trials will determine whether lowering uric acid level reduces the frequency of CAD and ischemic stroke.

Increased oxidative DNA damage in lean normoglycemic offspring of type 2 diabetic patients.

OBJECTIVE: Several studies have shown increased oxidative stress in patients with pre-diabetes and newly diagnosed Type 2 diabetes mellitus (T2DM). It has been proposed that oxidative stress initiates insulin resistance in genetically predisposed individuals. The aim of this study was to evaluate the markers of oxidative stress in the offspring of patients with T2DM. MATERIAL AND METHODS: We examined 60 lean normoglycemic offspring of Type 2 diabetics, and 52 age, sex and body mass index matched subjects without family history of T2DM as controls. Anthropometric, biochemical and carotid intima media thickness (IMT) measurements and oral glucose tolerance test (OGTT) were performed. Erythrocyte superoxide dismutase and glutathione peroxidase activities, serum nitric oxide, plasma total sulfhydryl (tSH) groups, plasma total antioxidant status, plasma malondialdehyde and serum 8-hydroxydeoxy-guanosine (8-OHdG) levels were compared between 2 groups. RESULTS: 2 groups were similar for the measurements of anthropometric, blood pressure, lipids, fasting glucose, HOMA-IR and carotid IMT. Glucose levels during OGTT were significantly higher in the offspring of Type 2 diabetics than controls (p=0.035). The offspring of Type 2 diabetics showed a significant increase in serum 8-OHdG level (p=0.005) and plasma tSH groups (p=0.032) when compared to the controls. Significant differences were not obtained in other oxidative stress marker levels between 2 groups. CONCLUSION: Main finding of our study was the presence of increased oxidative DNA damage in lean normoglycemic offspring of Type 2 diabetic patients. There is a need for further clinical studies in order to explain whether oxidative stress is present in genetically predisposed subjects and induces the insulin resistance.

Effects of Androctonus crassicauda (Olivier, 1807) (scorpiones: buthidae) venom on rats: correlation among acetylcholinesterase activities and electrolytes levels

Scorpions can be considered living fossils because they have changed so little during the last 400 million years. They are venomous arthropods of the Arachnida class and regarded as relatives of spiders, ticks and mites. The aim of the present study was to evaluate the toxicity of Androctonus crassicauda (Olivier, 1807) venom and its effects on the acetylcholinesterase (AchE) activity and on electrolytes levels in rats. Animals were divided into seven groups of five rats each. Test groups received 250æg/kg of venom solution while control group was treated with 200æl of physiological saline solution (PSS). Blood samples were collected from the animals on the 1st, 2nd 4th, 8th, 12th, and 24th hours after subcutaneous injection of venom. Animals were monitored for 24 hours. Androctonus crassicauda venom significantly reduced AchE activity on the 12th hour when compared with control group. A statistically negative correlation between Na+ and K+ (p<0.05) and a positive correlation between Na+ and CL- (p<0.001) ions levels were observed after the administration of A. crassiccauda venom to rats. We can conclude that the differences in the electrolytes levels are due to acute renal failure, since elimination of toxin occurs primarily via the kidney.(AU)

Evidence for single origins of 35delG and delE120 mutations in the GJB2 gene in Anatolia.

Eighteen different sequence changes, including three novel alterations, were detected in GJB2, encoding connexin 26, in 371 Turkish probands with non-syndromic sensorineural hearing loss. Two frequently detected mutations, 35delG and delE120, were shown to have single origins based on the conserved genotypes of two closely linked microsatellite and five single nucleotide polymorphism markers. Carrier frequencies of 35delG and delE120 in Egypt and Turkic populations of the Near East provide insights about the origin of these two mutations.

Biodegradable bromocryptine mesylate microspheres prepared by a solvent evaporation technique. I: Evaluation of formulation variables on microspheres characteristics for brain delivery.

The aim of this study was to formulate biodegradable microspheres containing an anti-parkinsonian agent, bromocryptine mesylate, for brain delivery. The effect of formulation parameters (e.g. polymer, emulsifying agent type and concentration) on the characteristics of the microspheres produced, the efficiency of drug encapsulation, the particle size distribution and in vitro drug release rates from the bromocryptine mesylate microspheres were investigated using a 3(2) factorial design. Bromocryptine mesylate was encapsulated into biodegradable polymers using the following three different polymers; poly(L-lactide), poly(D,L-lactide) and poly(D,L-lactide-co-glycolide). The SEM photomicrographs showed that the morphology of the microspheres greatly depended on the polymer and emulsifying agent. The results indicate that, regardless of the polymer type, increase in emulsifying agent concentration from 0.25-0.75% w/v markedly decreases the particle size of the microspheres. Determination of particle size revealed that the use of 0.75% w/v of emulsifying agent concentration and a polymer solution concentration of 10% w/v resulted in optimum particle size. In order to prepare biodegradable microspheres with high drug content and small particle size, selection of polymer concentration as well as emulsifying agent concentration is critical. Polymer type has a less pronounced effect on the percentage encapsulation efficiency and particle size of microspheres than on the t(50%). The microspheres prepared by all three polymers, at a polymer concentration of 10% w/v and an emulsifying agent concentration of 0.75% w/v with NaCMC:SO (4:1, w/v) mixture was as the optimum formulation.

Mitosis and apoptosis in canine cutaneous histiocytoma and transmissible venereal tumour.

Cell proliferation and apoptosis in canine cutaneous histiocytomas and transmissible venereal tumours were examined in twenty cases. The Ki-67 immunohistochemistry and Tunel methods were used to detect mitotic activity and apoptosis, respectively. The number of Ki-67 immunoreactive cells was 11.65 (+/- 1.1706) in canine cutaneous histiocytomas and 17 (+/- 2.1751) in transmissible venereal tumours. The mean values of apoptotic cells for canine cutaneous histiocytomas and transmissible venereal tumours were 13.25 (+/- 1.8758) and 8.52 (+/- 1.1007), respectively. It was considered that mitotic activity and apoptotic indices were useful in differentiation of canine cutaneous histiocytomas and transmissible venereal tumours. The correlation values for canine cutaneous histiocytomas and transmissible venereal tumours were 0.359 (+/- 0.330) and -0.232 (+/- 0.344), respectively. No significant (P > 0.05) correlation was found between mitosis and apoptosis in these two tumour types.

Serum carotenoids and uric acid levels in relation to cancer.

We studied the levels of serum total carotenoids and uric acid in newly diagnosed cancer cases. The levels of carotenoids and uric acid in serum samples from 94 subjects with cancer affecting different sites (21 breast, 26 head and neck, 13 lung, 17 genitourinary and 17 other sites) were compared with those of 92 controls who were matched for age, sex, Quetelet index and smoking history. Mean (+/- SE) levels of carotenoids were significantly lower among the cases than the controls (51.41 +/- 3.32 vs. 102.75 +/- 4.52 micrograms/dl, P < 0.001), when all the different sites were considered together. The mean (+/- SE) uric acid levels among cases and controls were 5.14 +/- 0.16 mg/dl and 4.21 +/- 0.18 mg/dl (P < 0.001), respectively. It was of interest that patients with genitourinary cancer had the lowest serum carotenoids levels, and the highest levels were found in patients with breast cancer. These results are informative but do not establish a causal link. There was no apparent association between serum urate levels and cancer site. The data presented here do not provide support for the protective antioxidant properties of uric acid in cancer.

Chitosan microspheres of diclofenac sodium: I. application of factorial design and evaluation of release kinetics.

In this study microspheres of diclofenac sodium, an anti-inflammatory agent, were prepared by utilizing a natural polysaccharide, chitosan-H. The objective of this investigation was to sustain the action of diclofenac sodium and to show the effect of various conditions on release kinetics. For this reason factorial design experiments were performed. The independent variables in the 3(3) factorial design were chitosan-H concentration, tripolyphosphate concentration and stabilization time, and in the 3(2) factorial design were chitosan-H and tripolyphosphate concentrations. The dependent variables, t50% and the total drug content were investigated by the polynomial equations. The release profiles were evaluated kinetically and the best fit was obtained by the Higuchi equation.

Physician stress: is it inevitable?

Early attempts to understand the causes of physician stress focused almost exclusively upon the role of external stressors and demands. Recent psychosocial and behavioral research, however, suggests that individual attitudes, beliefs, personality factors, and learned coping strategies probably play a more important role. In addition, such cognitive and behavioral tendencies are within the control of each individual, and clinical experience has shown that these factors can indeed be modified. Freudenberger noted that most health professionals who are experiencing high levels of stress fail to identify the role that they themselves play in generating such symptoms. Instead, they tend to blame others as the cause of their problems and tend to react cynically toward suggestions that they could benefit from help. A large-scale study of family physicians in North Carolina, conducted by May, Revicki, and Jones in 1983, confirmed the fact that most physicians who reported a high level of professional stress also tended to score high on measures of external locus of control--i.e. the perception that external or environmental factors are mainly responsible for one's problems or successes. My own experience in treating physicians and other people with stress tends to confirm these findings. More importantly, I have found that once individuals are helped to identify the role that their own cognitive and behavioral tendencies play in the origin of their stress, they can usually bring about impressive reductions in stress and tension without significant changes in environmental factors or demands. While many people advocate stress-releasing and other relaxation skills for physicians, I have found that such approaches are often counterproductive.(ABSTRACT TRUNCATED AT 250 WORDS)