Synthesis and biological activity of some new flavonyl-2,4-thiazolidinediones

A new series of flavonyl-2,4-thiazolidinediones (Va-c, VIa-c) was prepared by Knoevenagel reaction. The synthesized compounds were tested for their ability to inhibit rat kidney aldose reductase (AR) and for their insulinotropic activities in INS-1 cells. Compound Vb was able to increase insulin release in the presence of 5.6mmol/l glucose. Compounds VIa-c displayed moderate to high AR inhibitory activity levels. Particularly, compound VIa showed the highest AR inhibitory activity (86.57%).     

Insertion/deletion polymorphism of the angiotensin converting enzyme gene in coronary artery disease in southern Turkey

Genetic factors are important in the pathogenesis of coronary artery disease (CAD). Angiotensin converting enzyme (ACE) gene insertion(I)/deletion(D) polymorphism is one of the genetic factor found to be related with CAD. We investigated the association between I/D polymorphism of the ACE gene and the presence of CAD. Three hundred and seven patients (187 males and 120 females, aged between 35-80, mean 54.3 +/-9.8 years) who underwent diagnostic coronary angiography were included in the study. ACE I/D polymorphism was detected by polymerase chain reaction. Of the 307, 176 had CAD. The most frequently observed genotype in all subjects was ID (47.9 %). However, in patients with CAD the frequency of II genotype was lower whereas DD genotype was higher compared to the controls (p < 0.05). The number of D allele carrying subjects were also higher (p < 0.05) in CAD patients. The logistic regression analysis indicated that the ACE D allele is an independent risk factor (odds ratio = 1.48, 95 % CI = 1.01-2.18, p < 0.05). In conclusion, the I/D polymorphism of ACE gene (carrying D allele) is an independent risk factor for CAD in the studied Turkish population.     

Probiotic Potential and Gluten Hydrolysis Activity of Lactobacillus brevis KT16-2

Probiotics and Antimicrobial Proteins - Celiac disease (CD) is a chronic autoimmune disease that occurs in genetically predisposed individuals. Gluten-hydrolyzing probiotic bacteria are promising...     

Histological and immunohistochemical studies of the structure of lymph nodes in Kilis goats

Ten healthy adult Kilis goat mesenteric lymph nodes were used to examine the general structure of lymph nodes, lymphocytes, plasma cells, reticular cells and reticular fibers using histological methods. We also detected T lymphocytes using anti-CD3 [SP7], anti-CD4 [74-12-4], mouse anti-bovine CD4 [CC30] and mouse anti-bovine CD8 [CC63] monoclonal antibodies (mAb); and B lymphocytes using anti-CD79a [HM57] mAb, macrophages using anti-macrophage [MAC387] mAb and follicular dendritic cells using anti-S100 polyclonal antibody (pAb). The distribution of these cells also was studied. Although the primer antibodies we used for CD3, CD8, CD79a, MAC387 and S100 worked well, the primer antibodies for CD4 were ineffective for paraffin embedded goat lymph nodes.     

Reliability and validity of the modified Conconi test on concept II rowing ergometers

The purpose of this study was to assess the reliability and validity of the modified Conconi test on Concept II rowing ergometers. Twenty-eight oarsmen conducted 3 performance tests on separate days. Reliability was assessed using the break point in heart rate (HR) linearity called the Conconi test (CT) and Conconi retest (CRT) for the noninvasive measurement of anaerobic threshold (AT). Blood lactate measurement was considered the gold standard for the assessment of the AT, and the validity of the CT was assessed by blood samples taken during an incremental load test (ILT) on ergometers. According to the results, the mean power output (PO) scores for the CT, CRT, and ILT were 234.2 +/- 40.3 W, 232.5 +/- 39.7 W, and 229.7 +/- 39.6 W, respectively. The mean HR values at the AT for the CT, CRT, and ILT were 165.4 +/- 11.2 b.min, 160.4 +/- 10.8 b.min, and 158.3 +/- 8.8 b.min, respectively. Interclass correlation coefficient (ICC) analysis indicated a significant correlation between the 3 tests with one another. Also, Bland and Altman plots showed that there was an association between noninvasive tests and the ILT PO scores and HRs (95% confidence interval [CI]). In conclusion, this study showed that the modified CT is a reliable and valid method for determining the AT of elite men rowers.     

Neural network model of on-off units in the fly visual system: simulations of dynamic behavior

We analyze the dynamic properties of a neural network model for on-off spiking neurons recorded in the first optic chiasm of the fly visual system. The model consists of two parallel pathways and three sequential processing stages. The first stage models photoreceptors. At the second stage, the signal is segregated into on- and off-pathways. These pathways are proposed to correspond to two populations of amacrine cells. At the third stage, the on- and off-pathways converge to on-off neurons. Furthermore, according to the model, on-off neurons interact via recurrent connections. This stage is proposed to correspond to lamina L4 neurons. In response to luminance increments and decrements, the model exhibits a three-component response and suggests pathways for each of the components. When stimulated by a train of pulses, the model exhibits fast adaptation for frequencies higher than about 5 Hz. Furthermore, adaptation to on- and off-pulses occurs independently. When the frequency of stimulation is reduced, the unit recovers rapidly from its adapted state. The temporal modulation transfer function has its peak around 7 Hz. The phase characteristics show a phase lead for low temporal frequencies changing to a phase lag for high frequencies. These model predictions are compared with data from Jansonius and van Hateren (1991). Received: 26 May 1997 / Accepted in revised form: 19 February 1998     

Dysphagia in Acute Stroke: Incidence,Burden and Impact on Clinical Outcome

Background

Reported frequency of post-stroke dysphagia in the literature is highly variable. In view of progress in stroke management, we aimed to assess the current burden of dysphagia in acute ischemic stroke.

Methods

We studied 570 consecutive patients treated in a tertiary stroke center. Dysphagia was evaluated by using the Gugging Swallowing Screen (GUSS). We investigated the relationship of dysphagia with pneumonia, length of hospital stay and discharge destination and compared rates of favourable clinical outcome and mortality at 3 months between dysphagic patients and those without dysphagia.

Results

Dysphagia was diagnosed in 118 of 570 (20.7%) patients and persisted in 60 (50.9%) at hospital discharge. Thirty-six (30.5%) patients needed nasogastric tube because of severe dysphagia. Stroke severity rather than infarct location was associated with dysphagia. Dysphagic patients suffered more frequently from pneumonia (23.1% vs. 1.1%, p<0.001), stayed longer at monitored stroke unit beds (4.4±2.8 vs. 2.7±2.4 days; p<0.001) and were less often discharged to home (19.5% vs. 63.7%, p = 0.001) as compared to those without dysphagia. At 3 months, dysphagic patients less often had a favourable outcome (35.7% vs. 69.7%; p<0.001), less often lived at home (38.8% vs. 76.5%; p<0.001), and more often had died (13.6% vs. 1.6%; p<0.001). Multivariate analyses identified dysphagia to be an independent predictor of discharge destination and institutionalization at 3 months, while severe dysphagia requiring tube placement was strongly associated with mortality.

Conclusion

Dysphagia still affects a substantial portion of stroke patients and may have a large impact on clinical outcome, mortality and institutionalization.     

A novel model of early type 1 diabetes mellitus: The chick embryo air sack model

Diabetes Mellitus (DM) is a metabolic disease characterized by hyperglycemia. Chronic hyperglycemia is associated with long-term dysfunction such as retinopathy, nephropathy, neuropathy and cardiovascular diseases. These complications increase rates of death and disability worldwide. Due to the negative effects of DM on the quality of life, the mechanism and treatments of the disease should be investigated in more detail. Most of the research in diabetes is performed in experimental animals. Experimental animal models contributed to the advancement of clinical research, the development of new therapeutic approaches, the discovery of insulin and the purification of insulin. There are many animal models of DM in the literature. But there are a few DM model studies created with chick embryos. In these studies, it was seen that there were differences in STZ doses and STZ administration techniques. The objective of this study was to create a more acceptable and easier DM model. 180 specific pathogen free (SPF) fertilized chicken eggs (White Leghorn chicken) were used in this study. STZ was administered to 160 SPF eggs for an induced DM model. The remaining 20 SPF eggs were separated as a control group. We used two different DM models (Air sack model (ASM) and Chorioallantoic membrane model (CAMM)) and blood sampling technique in our study. 160 SPF eggs were divided into two groups with 80 eggs in each group, according to the model in which STZ was administered. When the relationship between blood glucose and blood insulin levels were examined, it was determined that there was a significantly strong negative correlation in the control group and ASM 1 group; and a significantly very strong negative correlation was found in the ASM 2 group and ASM 3 group. Our data indicate that the optimal STZ dose to create a DM model was 0.45 mg/egg and the best DM model was ASM. The second technique to be the best blood sampling technique for determining blood glucose levels. We believe that ASM can be used in DM studies and anti-DM drug studies in terms of its easebly, applicability, reproducibility and low cost.     

Bone marrow mesenchymal stem cell donors with a high body mass index display elevated endoplasmic reticulum stress and are functionally impaired

Bone marrow mesenchymal stem cells (BM‐MSCs) are promising candidates for regenerative medicine purposes. The effect of obesity on the function of BM‐MSCs is currently unknown. Here, we assessed how obesity affects the function of BM‐MSCs and the role of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) therein. BM‐MSCs were obtained from healthy donors with a normal (<25) or high (>30) body mass index (BMI). High‐BMI BM‐MSCs displayed severely impaired osteogenic and diminished adipogenic differentiation, decreased proliferation rates, increased senescence, and elevated expression of ER stress–related genes ATF4 and CHOP. Suppression of ER stress using tauroursodeoxycholic acid (TUDCA) and 4‐phenylbutyrate (4‐PBA) resulted in partial recovery of osteogenic differentiation capacity, with a significant increase in the expression of ALPL and improvement in the UPR. These data indicate that BMI is important during the selection of BM‐MSC donors for regenerative medicine purposes and that application of high‐BMI BM‐MSCs with TUDCA or 4‐PBA may improve stem cell function. However, whether this improvement can be translated into an in vivo clinical advantage remains to be assessed.     

The Ability to Generate Senescent Progeny as a Mechanism Underlying Breast Cancer Cell Heterogeneity

Background

Breast cancer is a remarkably heterogeneous disease. Luminal, basal-like, “normal-like”, and ERBB2+ subgroups were identified and were shown to have different prognoses. The mechanisms underlying this heterogeneity are poorly understood. In our study, we explored the role of cellular differentiation and senescence as a potential cause of heterogeneity.

Methodology/Principal Findings

A panel of breast cancer cell lines, isogenic clones, and breast tumors were used. Based on their ability to generate senescent progeny under low-density clonogenic conditions, we classified breast cancer cell lines as senescent cell progenitor (SCP) and immortal cell progenitor (ICP) subtypes. All SCP cell lines expressed estrogen receptor (ER). Loss of ER expression combined with the accumulation of p21^Cip1 correlated with senescence in these cell lines. p21^Cip1 knockdown, estrogen-mediated ER activation or ectopic ER overexpression protected cells against senescence. In contrast, tamoxifen triggered a robust senescence response. As ER expression has been linked to luminal differentiation, we compared the differentiation status of SCP and ICP cell lines using stem/progenitor, luminal, and myoepithelial markers. The SCP cells produced CD24+ or ER+ luminal-like and ASMA+ myoepithelial-like progeny, in addition to CD44+ stem/progenitor-like cells. In contrast, ICP cell lines acted as differentiation-defective stem/progenitor cells. Some ICP cell lines generated only CD44+/CD24-/ER-/ASMA- progenitor/stem-like cells, and others also produced CD24+/ER- luminal-like, but not ASMA+ myoepithelial-like cells. Furthermore, gene expression profiles clustered SCP cell lines with luminal A and “normal-like” tumors, and ICP cell lines with luminal B and basal-like tumors. The ICP cells displayed higher tumorigenicity in immunodeficient mice.

Conclusions/Significance

Luminal A and “normal-like” breast cancer cell lines were able to generate luminal-like and myoepithelial-like progeny undergoing senescence arrest. In contrast, luminal B/basal-like cell lines acted as stem/progenitor cells with defective differentiation capacities. Our findings suggest that the malignancy of breast tumors is directly correlated with stem/progenitor phenotypes and poor differentiation potential.