Long-acting pasireotide improves clinical signs and quality of life in Cushing's disease: results from a phase III study.

PURPOSE: Cushing's disease (CD) is associated with significant clinical burden, increased mortality risk, and impaired health-related quality of life (HRQoL). This analysis explored the effect of long-acting pasireotide on clinical signs of hypercortisolism and HRQoL in a large subset of patients with CD. METHODS: In this phase III study (clinicaltrials.gov: NCT01374906), 150 adults with CD and a mean urinary free cortisol (mUFC) level between 1.5 and 5.0 times the upper limit of normal (ULN) started long-acting pasireotide 10 or 30 mg every 28 days with dose increases/decreases permitted based on mUFC levels/tolerability (minimum/maximum dose: 5/40 mg). Changes in clinical signs of hypercortisolism and HRQoL were assessed over 12 months of treatment and were stratified by degree of mUFC control for each patient. RESULTS: Patients with controlled mUFC at month 12 (n = 45) had the greatest improvements from baseline in mean systolic (- 8.4 mmHg [95% CI - 13.9, - 2.9]) and diastolic blood pressure (- 6.0 mmHg [- 10.0, - 2.0]). Mean BMI, weight, and waist circumference improved irrespective of mUFC control. Significant improvements in CushingQoL total score of 5.9-8.3 points were found at month 12 compared with baseline, irrespective of mUFC control; changes were driven by improvements in physical problem score, with smaller improvements in psychosocial score. CONCLUSIONS: Long-acting pasireotide provided significant improvements in clinical signs and HRQoL over 12 months of treatment, which, in some cases, occurred regardless of mUFC control. Long-acting pasireotide represents an effective treatment option and provides clinical benefit in patients with CD. CLINICAL TRIAL REGISTRATION NUMBER: NCT01374906.

Comparison of the Ovary and Kidney as Sites for Islet Transplantation in Diabetic Rats.

BACKGROUND: Currently, the most commonly used site for clinical islet transplantation is the liver although it is far from being an ideal site. Low oxygen tension and the induction of an inflammatory response impair islet implantation and lead to significant early loss of islet. The present study aimed to investigate and compare the efficacy of islet transplantation to the ovary and kidney subcapsule in diabetic rats. METHODS: The study was performed with 3 groups of rats (control, ovary, and kidney subcapsule) including 6 Sprague female rats each. Diabetes model was created with the use of streptozotocin, and blood glucose levels of the rats were measured after 72 hours. Thirty days after the transplantation, blood samples were obtained from the rats, and then pancreas, kidney, and ovary specimens were fixed in 10% formaldehyde and the experiment completed. After staining with hematoxylin and eosin, the tissue samples were morphologically evaluated by a specialist histopathologist. RESULTS: Changes in mean blood glucose and C-peptide levels were statistically significant in the ovary and kidney subcapsule groups. Histologic examination revealed that granulosus insulin-bearing cells were detected in the islet grafts of both ovary and kidney subcapsule groups. The renal subcapsule group had inflammation signs on histologic examination. The islet cells of both ovary and renal subcapsule groups had no vacuolization. CONCLUSIONS: We showed that the ovary might be a new site for islet transplantation. Further research should be done on whether the initial results of this study can be reproduced in larger numbers of animal models and eventually in humans.

Bone health and vitamin D status in alcoholic liver disease.

Alcohol consumption is harmful to many organs and tissues, including bones, and it leads to osteoporosis. Hepatic osteodystrophy is abnormal bone metabolism that has been defined in patients with chronic liver disease (CLD), including osteopenia, osteoporosis, and osteomalacia. Decreased bone density in patients with CLD results from decreased bone formation or increased bone resorption. The prevalence of osteopenia in alcoholic liver disease (ALD) patients is between 34 % and 48 %, and the prevalence of osteoporosis is between 11 % and 36 %. Cirrhosis is also a risk factor for osteoporosis. The liver has an important role in vitamin D metabolism. Ninety percent of patients with alcoholic liver cirrhosis have vitamin D inadequacy (<80 nmol/L). The lowest serum vitamin D levels were observed in patients with Child-Pugh class C. Bone densitometry is used for the definitive diagnosis of osteoporosis in ALD. There are no specific controlled clinical studies on the treatment of osteoporosis in patients with ALD. Alcohol cessation and abstinence are principal for the prevention and treatment of osteoporosis in ALD patients, and the progression of osteopenia can be stopped in this way. Calcium and vitamin D supplementation is recommended, and associated nutritional deficiencies should also be corrected. The treatment recommendations of osteoporosis in CLD tend to be extended to ALD. Bisphosphonates have been proven to be effective in increasing bone mineral density (BMD) in chronic cholestatic disease and post-transplant patients, and they can be used in ALD patients. Randomized studies assessing the management of CLD-associated osteoporosis and the development of new drugs for osteoporosis may change the future. Here, we will discuss bone quality, vitamin D status, mechanism of bone effects, and diagnosis and treatment of osteoporosis in ALD.

Clinical significance of ADAMTS1, ADAMTS5, ADAMTS9 aggrecanases and IL-17A, IL-23, IL-33 cytokines in polycystic ovary syndrome.

PURPOSE: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age. A disintegrin and metalloproteinase with thrombospondin-like motifs (ADAMTS) are involved in inflammation and fertility. The aim of this investigation was to evaluate the serum levels of ADAMTS1, ADAMTS5, ADAMTS9, IL-17, IL-23, IL-33 and to find out the relationship between these inflammatory cytokines and ADAMTSs in PCOS patients. METHODS: A case-control study was performed in a training and research hospital. Eighty patients with PCOS and seventy-eight healthy female volunteers were recruited in the present study. Serum ADAMTS and IL levels were determined by a human enzyme-linked immunoassay (ELISA) in all subjects. RESULTS: The IL-17A, IL-23 and IL-33 levels were significantly higher in the PCOS patients compared to the controls (p < 0.05). We could not find significant difference between the groups in terms of ADAMTS1, ADAMTS5 and ADAMTS9 levels. IL-17A had positive correlations with LDL cholesterol and IL-33 and negative correlations with ADAMTS1, ADAMTS5, and ADAMTS9. IL-33 had positive correlation with LDL cholesterol and IL-17A. In ROC curve analysis, PCOS can be predicted by the use of IL-17A, IL-23 and IL-33 which at a cut-off value of 8.37 pg/mL (44 % sensitivity, 83 % specificity), 26.75 pg/mL (36 % sensitivity, 64 % specificity) and 14.28 pg/mL (83 % sensitivity, 39 % specificity), respectively. CONCLUSIONS: The results of the study might suggest that ADAMTS and IL molecules have a role in the pathogenesis of the PCOS. Further efforts are needed to establish causality for ADAMTS-IL axis.

Usefulness of the neutrophil-to-lymphocyte ratio to prediction of type 2 diabetes mellitus in morbid obesity.

BACKGROUND: There is growing consensus in the literature that inflammation plays a central role in the pathophysiology of obesity and type 2 diabetes mellitus (T2DM) and cardiovascular complications. Neutrophil-to-lymphocyte ratio (NLR) provides a simple method for assessment of inflammatory status and it is a new, inexpensive marker. The aim of the present study was to investigate the predictive value of preprocedural (before the OGTT) NLR on development of type 2 diabetes (T2DM) in morbid obesity patients (MOP). METHODS: 306 MOP (body mass index ≥ 40 kg/m(2)) and 95 normal weight patients with normal OGTT [fasting plasma glucose (FPG)<100mg/dL. Two-hour glucose during OGTT<140 mg/dL] were evaluated in this study. RESULTS: The mean ± SD NLR of MOP was significantly higher than that of patients with normal weight healthy patients (3.67 ± 0.95 vs. 1.82 ± 1.02, P<0.001, respectively). In receiver operating characteristics curve analysis, NLR>3.12 had 79.2% sensitivity and 64.9% specificity in predicting T2DM. Logistic regression analysis showed that elevated NLR (OR: 2.577, 95% CI: 1.363-4.872, P=0.004) was an independent variable for predicting T2DM in MOP. CONCLUSIONS: MOP have higher NLR than healthy controls. High NLR is a powerful and independent predictor of T2DM in MOP. Elevated NLR levels are usually considered as an inflammatory marker. The results of this study suggested that inflammation plays a role in the pathogenesis of T2DM with MOP.

Serum nesfatin-1 levels in overt and subclinical hyperthyroidism.

AIM: Nesfatin-1 was recently discovered anorexigenic peptide in the brain which is derived from nucleobindin-2. Central and peripheral administration of nesfatin-1, inhibits food intake, dose-dependently. Hyperthyroid patients have increased appetite and food intake with a craving for carbohydrate-rich food, at the beginning of disease, but the physiological mechanisms underlying this behavior is not known exactly. In this study, we investigated whether nesfatin-1 is involved in the regulation of appetite and body weight in hyperthyroidism, or not. METHODS: A total of 70 patients with subclinical (35) and overt hyperthyroidism (35) compared with 35 control patients. Serum nesfatin-1 level was measured from all samples by commercial ELISA kit. RESULTS: Serum nesfatin-1 levels were similar between three groups (P=0.293). After adjusting for age and body mass index, nesfatin-1 levels in control group was not different from subclinical and overt hyperthyroid group, respectively (P=0.567 and P=0.519). CONCLUSION: These data showed that serum nesfatin-1 levels do not significant change in overt and subclinical hyperthyroidism.

Effect of stem cell application on Asherman syndrome, an experimental rat model.

PURPOSE: We evaluate the effect of stem cells to induce endometrial proliferation and angiogenesis on Asherman Syndrome (AS). METHODS: The experimental study was performed in stemcell research laboratory. Forty Wistar-Albino rats were divided according to groups. In group1 (n = 10) to establish the model; trichloroacetic acid was injected to right uterine horn. Two weeks later, intrauterine synechia was confirmed. In group2 (n = 10), 2 weeks later, 2 × 106 mesenchymal stem cells (MSC) were injected into right uterine horn followed by three intraperitoneal injections of MSCs. In group3 (n = 10), daily oral estrogen was initiated on the second week. In group4 (n = 10), MSC injections and oral estrogen was given together. The amount of fibrosis, vascularisation, inflammation and immunohistochemical staining with vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA) and Ki-67 were evaluated in the uterine tissues. RESULTS: In all treatment groups; fibrosis decreased but vascularisation and immunhistohemical stainings increased in the experimental side. The amount of fibrosis, vascularisation, Ki-67 and PCNA scores were similar between group2 and 3. In group4, comparing to group2, less fibrosis but more Ki-67, PCNA and VEGF staining was observed. CONCLUSION: Stem cells, when added to estrogen, are a highly effective alternative to induce regeneration of endometrium in Asherman Syndrome therapy.

The effect of feto-maternal blood type incompatibility on development of gestational diabetes mellitus.

OBJECTIVE: To assess the relation between fetal and maternal blood type (ABO, Rh) incompatibility and development of gestational diabetes mellitus (GDM). MATERIALS AND METHODS: A total of 500 pregnant women underwent diagnostic test for GDM by a 100-g oral glucose tolerance test (OGTT) after an 8 to 12-h overnight fast participated in this study. OGTT was performed between the 24-28 weeks of gestation, but participants who were at high risk for GDM were tested after the first prenatal visit. In the postpartum period, maternal and infant blood types were determined. Presence of GDM was evaluated in terms of matched and unmatched fetal and maternal ABO and Rh blood types separately. RESULTS: GDM was detected in 235 participants. Unmatched ABO blood types between the mother-infant pairs were present in 44.7% (n=105) of GDM (+) and 35.8 % (n=95) of GDM (-) patients. Incompatible feto-maternal ABO blood type was positively correlated with development of GDM which was marginally significant. (p=0.045; R=1.2;95% CL; 1.004-1.48). However, Rh feto-maternal blood type incompatibility was not related with development of GDM. CONCLUSIONS: Feto-maternal ABO blood type incompatibility may be a weak risk factor for the development of GDM.

Relationship of vaspin and apelin levels with insulin resistance and atherosclerosis in metabolic syndrome.

AIMS: We aimed to investigate, circulating vaspin, apelin-12 and apelin-36 levels in subjects with metabolic syndrome (MetS) and also to search for the association of vaspin and apelin levels with insulin resistance (IR), high sensitivity C-reactive protein (HsCRP), Carotid Artery Intima-Media Thickness (CIMT) and cardiovascular risk factors. METHODS: In this observational case-control study, a total of forty one patients with MetS (30 women and 11 men mean age, 41.3±9.4 years) and thirty nine healthy comparison subjects (27 women and 12 men; mean age, 38.4±6.1 years) were enrolled. Serum HsCRP, lipid profile, insulin levels and the homeostasis model assessment of insulin resistance (HOMA-IR) were evaluated. Apelin-12, apelin-36 and vaspin serum levels were measured via ELISA. High-resolution B-mode ultrasonography was performed. RESULTS: The two study groups did not differ as to age, sex, blood pressure, smoking history. Vaspin, apelin-12 and apelin-36 levels were significantly elevated in patients with MetS when compared with that of control subjects (P<0.001). Serum vaspin levels showed a statistically significant association with CIMT (r=0.365, P<0.001) and HsCRP (r=0.316, P<0.01) levels, whereas both serum apelin-12 and 36 levels were positively correlated with HOMA-IR (r=0.344/0.462 P<0.01). CONCLUSION: Based on the findings of this study, Serum vaspin and apelin levels were found significantly higher in patients with MetS than age-matched control subjects and significantly associated with coronary atherosclerosis. These adipocytokines might play a part in the pathogenesis of MetS. Also serum Apelin levels can be used as specific markers for insulin sensitivity in patients with MetS.

Cardiovascular risk factors, carotid artery intima media thickness, and HSCRP levels in patients with impaired glucose metabolism.

AIM: The aim of this paper was to compare serum high sensitivity C-reactive protein (HsCRP) levels and carotid artery intima-media thickness (CIMT) of patients with impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) with that in control subjects. METHODS: Ninety-six subjects with prediabetes, 48 with IFG, of mean age 50.7±11.3 years, and 48 with IGT, of mean age 50.9±12.3 years, were enrolled, along with 44 age-, sex-, and body mass index-matched controls with normal glucose tolerance. Serum HsCRP, lipid profile, insulin levels and the homeostasis model assessment of insulin resistance (HOMA-IR) was evaluated. High-resolution B-mode ultrasonography was performed. RESULTS: Serum HsCRP levels were significantly elevated in pre-diabetic patients when compared with that of control subjects. Median HsCRP values were 3.1 mg/L in IFG group, 3.47 mg/L in IGT group, and 1.5 mg/L in the controls (P<0.001). CIMT was significantly higher in pre-diabetic groups than that in the control group (IFG: 0.612±0.09; IGT: 0.625±0.1; control: 0.517±0.09, P<0.001). CIMT and HsCRP levels were similar in pre-diabetic groups. CIMT values were positively correlated with HsCRP (r=0.793, P=0.000), age (r=0.435, P=0.000), waist-hip ratio (r=0.170, P=0.044), fasting plasma glucose (r=0.302, P=0.000), HOMA-IR (r=0.173, P=0.041), and low-density lipoprotein cholesterol (r=0.168, P=0.047) levels. CONCLUSION: Both IFG and IGT were associated with increased cardiovascular risk as assessed by serum hsCRP levels and CIMT. In contrast to previous studies, risk appears to be the same in the two categories of prediabetes.

Is NAFLD an independent risk factor for increased IMT in T2DM?

AIM: Recent data have suggested that the presence of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus may also be linked to increased risk of cardiovascular disease (CVD) independent from metabolic syndrome. Therefore the aim of the study is to compare the CVD risk in diabetic and non diabetic participants and to evaluate whether there is an association betweeen NAFLD and CVD risk. METHODS: Fifty five type 2 diabetic (study group) and 44 nondiabetic patients (control group) were included in the study. Patients were divided into two groups according to degree of hepatosteatosis. Group 1 include grade≥2 hepatosteatosis and group 2 include grade<2 hepatosteatosis patients. RESULTS: As a result, hepatosteatosis rates were found to be similar in diabetic and non-diabetic patients (P=0.07). Mean CIMT was significantly higher in diabetic patients (P=0.01). Mean fasting plasma glucose (FPG) and glucolise hemoglobin (HbA1c) were found to be higher in grade≥2 hepatosteatosis group (P=0.002 and 0.004 respectively). But CIMT was found to be similar between hepatosteatosis groups (P=0.618). CONCLUSION: NAFLD is extremely common in people with type 2 diabetes and is mainly associated with uncontrolled diabetes. CIMT values as cardiovascular risk assessment were found to be significantly higher in diabetic patients regardless degree of hepatosteatosis.

The relation of serum 25-hydroxyvitamin-D levels with severity of obstructive sleep apnea and glucose metabolism abnormalities.

Obstructive sleep apnea (OSA) and 25-hydroxyvitamin-D3 (25-OH-D) deficiency are two separate disorders associating with obesity, inflammation, and impaired glucose metabolism. We aimed to investigate the vitamin D status of OSA patients regarding to potential links between lower vitamin D levels and abnormal glucose metabolism, which is one of the main adverse outcomes of OSA. Study group is composed of 190 non-diabetic subjects who were suspected of having OSA. Subjects undergone polysomnography and were grouped due to apnea-hypopnea indices (AHI) as controls (AHI < 5, n = 47), mild OSA (5 ≤ AHI < 15, n = 46), moderate OSA (15 ≤ AHI < 30, n = 47), and severe OSA (AHI ≥ 30, n = 50). Serum 25-OH-D, HbA1c, insulin levels were measured and 75-g oral glucose tolerance test was performed. Serum 25-OH-D level (ng/ml) of OSA patients were lower than control subjects (17.4 ± 6.9 vs. 19.9 ± 7.8), and decrement was parallel to severity of OSA; as 18.2 ± 6.4 (5 ≤ AHI < 15), 17.5 ± 7.4 (15 ≤ AHI < 30), and 16.3 ± 6.9 (AHI > 30), respectively (P = 0.097, r = -0.13). However, severe female OSA patients had significantly lower 25-OH-D levels (11.55 ng/ml), while control males had the highest mean value (21.7 ng/ml) (P < 0.001). Frequency of insulin resistance (IR) was 48%, prediabetes 41%, diabetes 16% in OSA patients. Mean 25-OH-D level of insulin resistant subjects (HOMA-IR ≥ 2.7, n = 77, AHI = 35.5) was lower than non-insulin resistant subjects (HOMA-IR < 2.7, n = 113, AHI = 19.8) as 16.18 ± 7.81 versus 19.2 ± 6.6, respectively (P = 0.004). 25-OH-D level of 91 non-diabetic subjects (n = 91, AHI = 19.7) was 19.5 ± 7.4, prediabetics (n = 75, AHI = 28.7) was 17.45 ± 6.9, and diabetics (n = 24, AHI = 46.3) was 13.8 ± 5.3 (P = 0.02). We showed that subjects with more severe OSA indices (AHI ≥ 15) tended to present lower vitamin D levels correlated to increased prevalence of IR, prediabetes, and diabetes. Vitamin D deficiency may play a role and/or worsen OSA's adverse outcomes on glucose metabolism. OSA patients may be considered for supplementation treatment which was shown to ameliorate abnormal glucose metabolism and inflammation.

Oxidative stress markers are not valuable markers in lean and early age of polycystic ovary syndrome patients.

BACKGROUND: Early atherosclerosis and increased risk of cardiovascular diseases (CVD) have been reported in patients with polycystic ovary syndrome (PCOS). Oxidative stress is an accepted risk factor for the development of CVD. AIM: To evaluate the association between oxidative stress markers [ischemia-modified albumin (IMA), total antioxidant status (TAS), and total oxidant status (TOS) levels], carotid intima- media thickness (CIMT), endocrine and metabolic parameters in patients with PCOS. MATERIALS, SUBJECTS, AND METHODS: We studied 52 patients with PCOS and 36 age- and body mass index (BMI)-matched controls. The diagnosis of PCOS was made according to the Rotterdam criteria. Metabolic, hormonal parameter and IMA, TAS, TOS levels were measured. RESULTS: No statistically significant difference was determined in relation to age, BMI and waist-hip ratio, IMA, TAS, and TOS levels between groups. Mean IMA level was higher in PCOS patients, however, statistical significant difference was not observed. Mean CIMT and homeostasis model assessment of insulin resistance levels were significantly higher in patients with PCOS than in control subjects. CONCLUSION: Our study has shown that although CIMT levels, showing CVD risk, were higher in PCOS patients, TAS and TOS oxidative stress markers were found to be similar between groups, IMA was higher in PCOS patients however the difference was not reach statistical significant. The present results suggest that CIMT increases before the state of ischemia and shows preischemic state of vasculature, while oxidative stress markers are considered to be indicators of ischemia and reperfusion injury in progressive vascular disease. Further studies are needed to show the association between oxidative stress markers, CVD and PCOS.

Somatotropin adenoma and resistance to thyroid hormone.

Resistance to thyroid hormone (RTH) is a rare disease characterized by non-suppressed TSH in spite of high free thyroid hormone levels. Up to date, in the literature, there are more than 600 RTH cases, but co-incidental hypophyseal adenoma was reported in only 1 case. In the literature, despite reported cases with thyrotropinoma accompanying RTH, we could not find a case with somatotropinoma accompanying RTH. Here, we report a 34-yr-old male patient, who was admitted to the hospital with complaints of dyspnea, chest pain, and palpitation in 2003. His alpha- subunit value was normal and the alpha-subunit/TSH molar ratio was <1. His response to TRH stimulation test was normal. His TSH level was suppressed in the T3 suppression test. Hypophyseal magnetic resonance imaging showed a 6-mm hypophyseal microadenoma. Levels of all anterior hypophyseal hormones, including GH and IGF-I, were normal. Oral glucose tolerance test (OGTT)-GH suppression test was normal. The patient was followed with the diagnosis of RTH and incidental hypophyseal adenoma. After 3 yr, because of high levels of IGF-I: 901 ng/ml (68-324), the OGTT-GH suppression test was reported and no suppression was detected. Thus, the patient was referred to surgery with the pre-diagnosis of RTH and acromegaly. Immunohistochemistry was showed as strong GH staining with low Ki 67 index while TSH and other anterior hypophyseal hormones stainings were negative. Post-operative thyroid hormones were still high.

Effects of leptin replacement on macro- and micronutrient preferences.

BACKGROUND: The mechanisms underlying food choices are complex and involve neuroendocrine and biochemical signaling. Among neuroendocrine signals, leptin may play a prominent role in food preference. OBJECTIVE: This study was designed to obtain an understanding of the effects of leptin replacement on macro- and micronutrient preferences in leptin-deficient adults. DESIGN: We studied the effects of leptin replacement on three adults with genetic leptin deficiency during the initial 12 months of treatment. Dietary intake was measured in our study by weighed food consumption records. Nutrient intake was calculated using a nutrition analysis software. RESULTS: After leptin replacement was started, all patients had initially a marked reduction in food intake. The reduction in caloric intake differentially affected intake of macro- and micronutrients. There was an initial shift toward a higher percentage consumption of fats and a decrease in the intake of carbohydrates. Significant differences also occurred in 7 distinct types of macronutrients, 12 vitamins, 11 minerals and 1 amino acid. CONCLUSIONS: We documented several specific leptin-induced changes in macro- and micronutrients intake during the course of leptin-replacement treatment, the majority of which were not related to the decrease in total caloric consumption.

Effect of peritoneal dialysis solution type on serum lipid levels in end-stage renal disease.

Among the different cardiovascular risk factors, lipid abnormalities dominate the high mortality in chronic ambulatory peritoneal dialysis patients. So far, no data comparing the effect of standard glucose-containing, amino acid-containing, and icodextrin-containing peritoneal dialysis solutions on serum lipid concentrations in a chronic ambulatory peritoneal dialysis population are available. To determine the effect of peritoneal dialysis solutions on parameters of lipid metabolism, 67 subjects who had continued their usual dialysis for the last six months were enrolled in the study. Group A consisted of 18 patients who were receiving only glucose-based peritoneal dialysis solutions, group B consisted of 18 patients who were receiving glucose and amino acid-based peritoneal dialysis solutions, and group C consisted of 31 patients who were receiving glucose and icodextrin-based peritoneal dialysis solutions. Serum lipid parameters including total cholesterol, low-density lipoprotein, high-density lipoprotein, triglyceride, and lipoprotein (a) were determined in all groups. No significant difference in serum lipid parameters was found between groups A, B, and C. These results demonstrate the lack of the effect of amino acid or icodextrin-based peritoneal solutions on dyslipidemia of CAPD patients.

Platelet Functions in Patients with Allergic Asthma.

To investigate platelet functions in patients suffering from allergic diseases including asthma, blood was collected from ten asthmatic patients (five females, five males) and ten healthy controls (five females, five males) and by using whole-blood electrical impedance system; platelet count and platelet aggregation studies (maximum aggregation extent, maximum aggregation rate) were performed. Allergy screening was performed with skin test reactions and with high total and specific immunoglobulin E levels (CAP-Phadiatop system). Platelet count (333.1 ± 41.1 x 109/L), collagen induced the response of platelet aggregation (12.95 ± 4.19) and maximum rate of aggregation (8.00 ± 5.22) in allergic patients were found significantly higher than those of controls (252.1 ± 49.1 x 109/L; 8.33 ± 1.19; 4.28 ± 1.31) (p< 0.05). Also ADP induced response of platelet aggregation (18.21 ± 3.56) and maximum rate of aggregation (10.64 ± 2.12) in asthmatic patients were higher than controls (12.37 ± 2.63; 7.80 ± 1.64) with statistical significance (p< 0.01). Secretion products of activated platelets such as histamine, serotonin, PGF2α and PAF may play role in bronchial responsiveness in allergic asthma. The results of this study showed that platelet function tests were effected in asthmatic patients. The changes in platelet functions are thought to be related with increased IgE levels and stimulation of platelets by these antibodies.

Prevention of lens damage associated with cigarette smoke exposure in rats by alpha-tocopherol (vitamin E) treatment.

PURPOSE: To evaluate the possible protective effect and mechanism of alpha-tocopherol (vitamin E) treatment on lens degeneration associated with in vivo exposure to cigarette smoke and to further clarify the role of iron in cigarette smoke-generated lens damage. METHODS: Twenty-eight male Wistar rats were randomly divided into four equal groups. Rats in groups 3 and 4 were exposed to cigarette smoke for 1 hour each day over 90 consecutive days, and rats in groups 1 and 2 were treated in similar fashion but only exposed to room air. Additionally, vitamin E was given to the rats in groups 2 and 4 via intramuscular route. At the end of the study, both eyes of all the animals were enucleated; one eye was prepared for histopathologic examination, and the fellow eye was used for the measurement of iron and calcium levels. RESULTS: Significantly higher iron and calcium levels were observed in the lenses of group 3 rats than in other groups. Similar comparisons performed between groups 1 and 2, groups 1 and 4, and groups 2 and 4 did not show any significant difference. Distinct histopathologic changes in the anterior lens epithelium, such as hyperplasia, hypertrophy, epithelial multilayering, and the presence of epithelial cells over posterior lens capsule, observed in group 3 rats were not present in other groups. CONCLUSIONS: Cataractogenesis after cigarette smoke exposure was associated with an accumulation of iron and calcium in the rat lens, and vitamin E supplementation protected such accumulations and cataractogenesis.