Can the hydrogel form of sodium ascorbate be used to reverse compromised resin infiltrant penetration after bleaching?

Aims: The aim of this study was to investigate the effects of an antioxidant on the bleaching-induced reduction in the penetration depth of infiltrant resins. Materials and Methods: White spot lesions (WSLs) were created on 105 bovine tooth samples, each measuring 6 × 4 × 4 mm. Five samples were randomly selected for the examination of lesion characteristics. The remaining 100 samples were then divided into four groups (n = 25). In Group I, the WSLs were treated with resin infiltration (RI) only. RI was performed on Group II immediately after bleaching. In Group III, an antioxidant was applied for 2 h after bleaching, and this was immediately followed by RI. The Group IV samples were treated with RI at the end of a 1-week waiting period after bleaching. The penetration depths were evaluated through confocal laser scanning microscopy. Results: The lowest penetration rate, which was approximately 57%, was observed in Group II. This was followed by Group III (87%), Group IV (90%), and Group I (92%). Group II, in which the samples were infiltrated immediately after bleaching, had the lowest mean penetration percentage. All the bleached groups exhibited significantly lower penetration percentages than the nonbleached group (Group I) (P < 0.05). Antioxidant application increased the penetration significantly (P < 0.05). Conclusion: Application of sodium ascorbate was found to reverse the reduced resin penetration depth and penetration percentages resulting from bleaching. The postponement of adhesive procedures after bleaching yielded similar results.

Effect of in situ exopolysaccharide production on physicochemical, rheological, sensory, and microstructural properties of the yogurt drink ayran: an optimization study based on fermentation kinetics.

Exopolysaccharide (EPS)-producing starter cultures are preferred for the manufacture of fermented milk products to improve rheological and technological properties. However, no clear correlation exists between EPS production and the rheological and technological properties of fermented milk products such as the yogurt drink ayran. In this study, 4 different strain conditions (EPS- and EPS+ Streptococcus thermophilus strains) were tested as a function of incubation temperature (32, 37, or 42°C) and time (2, 3, or 4 h) to determine the effect of culture type and in situ EPS production on physicochemical, rheological, sensory, and microstructural properties of ayran. Furthermore, we assessed the effect of fermentation conditions on amounts of EPS production by different EPS-producing strains during ayran production. A multifactorial design of response surface methodology was used to model linear, interaction, and quadratic effects of these variables on steady shear rheological properties of ayran samples and in situ EPS production levels. The physicochemical and microbiological characteristics of ayran samples altered depending on incubation conditions and strain selection. Steady shear tests showed that ayran samples inoculated with EPS+ strains exhibited pseudoplastic flow behavior. Production of ayran with EPS- strain (control sample) resulted in the lowest apparent viscosity values (η50), whereas those produced with the combination of 2 EPS+ strains yielded ayran with notably increased η50 values. We concluded that incubation time was the variable with the greatest effect on η50, consistency coefficient (K), and flow behavior index (n) values. In situ EPS production was also affected by these conditions during ayran fermentation in which strain-specific metabolism conditions were found to be the most important factor for EPS production. In addition, these findings correlated the amount of in situ EPS produced with the rheological properties of ayran. Scanning electron microscopy images of the samples showed differences in structural features, revealing a prominent network strand structure in the ayran samples inoculated with the admixture of 2 EPS-producing strains incubated at 37°C for 3 h. These results provide useful information for large-scale production of ayran by the dairy industry.

Biodistribution of radiolabeled alpha-amanitin in mice: An Investigation.

Mushroom poisonings caused by Amanita phalloides are the leading cause of mushroom-related deaths worldwide. Alpha-Amanitin (α-AMA), a toxic substance present in these mushrooms, is responsible for the resulting hepatotoxicity and nephrotoxicity. The objective of our study was to determine the distribution of α-AMA in Balb/c mice by labeling with Iodine-131. Mice were injected with a toxic dose (1.4 mg/kg) of α-AMA labeled with Iodine-131. The mice were sacrificed at the 1st, 2nd, 4th, 8th, 24th, and 48th hours under anesthesia. The organs of the mice were removed, and their biodistribution was assessed in all experiments. The percent injected dose per gram (ID/g %) value for kidney, liver, lung, and heart tissues at 1st hour were 1.59 ± 0.07, 1.25 ± 0.33, 3.67 ± 0.80 and 1.07 ± 0.01 respectively. This study provides insights into the potential long-term effects of α-AMA accumulation in specific organs. Additionally, this study has generated essential data that can be used to demonstrate the impact of antidotes on the biological distribution of α-AMA in future toxicity models.

Review: Cancer and neurodevelopmental disorders: multi-scale reasoning and computational guide.

The connection and causality between cancer and neurodevelopmental disorders have been puzzling. How can the same cellular pathways, proteins, and mutations lead to pathologies with vastly different clinical presentations? And why do individuals with neurodevelopmental disorders, such as autism and schizophrenia, face higher chances of cancer emerging throughout their lifetime? Our broad review emphasizes the multi-scale aspect of this type of reasoning. As these examples demonstrate, rather than focusing on a specific organ system or disease, we aim at the new understanding that can be gained. Within this framework, our review calls attention to computational strategies which can be powerful in discovering connections, causalities, predicting clinical outcomes, and are vital for drug discovery. Thus, rather than centering on the clinical features, we draw on the rapidly increasing data on the molecular level, including mutations, isoforms, three-dimensional structures, and expression levels of the respective disease-associated genes. Their integrated analysis, together with chromatin states, can delineate how, despite being connected, neurodevelopmental disorders and cancer differ, and how the same mutations can lead to different clinical symptoms. Here, we seek to uncover the emerging connection between cancer, including pediatric tumors, and neurodevelopmental disorders, and the tantalizing questions that this connection raises.

Striatin knock out induces a gain of function of INa and impaired Ca2+ handling in mESC-derived cardiomyocytes.

AIM: Striatin (Strn) is a scaffold protein expressed in cardiomyocytes (CMs) and alteration of its expression are described in various cardiac diseases. However, the alteration underlying its pathogenicity have been poorly investigated. METHODS: We studied the role(s) of cardiac Strn gene (STRN) by comparing the functional properties of CMs, generated from Strn-KO and isogenic WT mouse embryonic stem cell lines. RESULTS: The spontaneous beating rate of Strn-KO CMs was faster than WT cells, and this correlated with a larger fast INa conductance and no changes in If. Paced (2-8 Hz) Strn-KO CMs showed prolonged action potential (AP) duration in comparison with WT CMs and this was not associated with changes in ICaL and IKr. Motion video tracking analysis highlighted an altered contraction in Strn-KO CMs; this was associated with a global increase in intracellular Ca2+, caused by an enhanced late Na+ current density (INaL) and a reduced Na+/Ca2+ exchanger (NCX) activity and expression. Immunofluorescence analysis confirmed the higher Na+ channel expression and a more dynamic microtubule network in Strn-KO CMs than in WT. Indeed, incubation of Strn-KO CMs with the microtubule stabilizer taxol, induced a rescue (downregulation) of INa conductance toward WT levels. CONCLUSION: Loss of STRN alters CMs electrical and contractile profiles and affects cell functionality by a disarrangement of Strn-related multi-protein complexes. This leads to impaired microtubules dynamics and Na+ channels trafficking to the plasma membrane, causing a global Na+ and Ca2+ enhancement.

Neurodevelopmental disorders and cancer networks share pathways, but differ in mechanisms, signaling strength, and outcome.

Epidemiological studies suggest that individuals with neurodevelopmental disorders (NDDs) are more prone to develop certain types of cancer. Notably, however, the case statistics can be impacted by late discovery of cancer in individuals afflicted with NDDs, such as intellectual disorders, autism, and schizophrenia, which may bias the numbers. As to NDD-associated mutations, in most cases, they are germline while cancer mutations are sporadic, emerging during life. However, somatic mosaicism can spur NDDs, and cancer-related mutations can be germline. NDDs and cancer share proteins, pathways, and mutations. Here we ask (i) exactly which features they share, and (ii) how, despite their commonalities, they differ in clinical outcomes. To tackle these questions, we employed a statistical framework followed by network analysis. Our thorough exploration of the mutations, reconstructed disease-specific networks, pathways, and transcriptome levels and profiles of autism spectrum disorder (ASD) and cancers, point to signaling strength as the key factor: strong signaling promotes cell proliferation in cancer, and weaker (moderate) signaling impacts differentiation in ASD. Thus, we suggest that signaling strength, not activating mutations, can decide clinical outcome.

Neurodevelopmental disorders, like cancer, are connected to impaired chromatin remodelers, PI3K/mTOR, and PAK1-regulated MAPK.

Neurodevelopmental disorders (NDDs) and cancer share proteins, pathways, and mutations. Their clinical symptoms are different. However, individuals with NDDs have higher probabilities of eventually developing cancer. Here, we review the literature and ask how the shared features can lead to different medical conditions and why having an NDD first can increase the chances of malignancy. To explore these vital questions, we focus on dysregulated PI3K/mTOR, a major brain cell growth pathway in differentiation, and MAPK, a critical pathway in proliferation, a hallmark of cancer. Differentiation is governed by chromatin organization, making aberrant chromatin remodelers highly likely agents in NDDs. Dysregulated chromatin organization and accessibility influence the lineage of specific cell brain types at specific embryonic development stages. PAK1, with pivotal roles in brain development and in cancer, also regulates MAPK. We review, clarify, and connect dysregulated pathways with dysregulated proliferation and differentiation in cancer and NDDs and highlight PAK1 role in brain development and MAPK regulation. Exactly how PAK1 activation controls brain development, and why specific chromatin remodeler components, e.g., BAF170 encoded by SMARCC2 in autism, await clarification.

Performance Assessment of the Network Reconstruction Approaches on Various Interactomes.

Beyond the list of molecules, there is a necessity to collectively consider multiple sets of omic data and to reconstruct the connections between the molecules. Especially, pathway reconstruction is crucial to understanding disease biology because abnormal cellular signaling may be pathological. The main challenge is how to integrate the data together in an accurate way. In this study, we aim to comparatively analyze the performance of a set of network reconstruction algorithms on multiple reference interactomes. We first explored several human protein interactomes, including PathwayCommons, OmniPath, HIPPIE, iRefWeb, STRING, and ConsensusPathDB. The comparison is based on the coverage of each interactome in terms of cancer driver proteins, structural information of protein interactions, and the bias toward well-studied proteins. We next used these interactomes to evaluate the performance of network reconstruction algorithms including all-pair shortest path, heat diffusion with flux, personalized PageRank with flux, and prize-collecting Steiner forest (PCSF) approaches. Each approach has its own merits and weaknesses. Among them, PCSF had the most balanced performance in terms of precision and recall scores when 28 pathways from NetPath were reconstructed using the listed algorithms. Additionally, the reference interactome affects the performance of the network reconstruction approaches. The coverage and disease- or tissue-specificity of each interactome may vary, which may result in differences in the reconstructed networks.

Does pendimethalin develop in pancreatic cancer induced inflammation?

Pendimethalin, one of the dinitroaniline group herbicides, is applied for controlling weeds in cereals, legumes and vegetable crops, and has been classified as possible human carcinogen. It is indicated that pendimethalin should arise risks of developing some cancer types; however, there is no data on the effects of pendimethalin on pancreatic cancer-induced inflammation. Injuries resulting from by acute pancreatitis attacks and inflammation are significant factors in the development of pancreatic cancer. Therefore, we investigated whether pendimethalin triggers inflammation as a mechanism of pancreatic cancer development. Parameters related to pancreatic activation, oxidative stress, and inflammation were measured in the human pancreatic (PANC-1) cell line. In the range of 0-100 µM, the levels of chymotrypsin decreased. It should be indicated that the reason for the decrease in chymotrypsin may be the high rates of cell death (20%) observed in the high concentration levels. We observed that pendimethalin significantly induced oxidative damage, while levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) did not change. The obtained results may draw attention to the usage and possible toxic effect of pendimethalin due to oxidative damage induction; however, detailed inflammation mechanisms and other cancer pathways should be investigated.

Short and long term outcomes after small-incision lenticule extraction: A tertiary referral centre experience.

PURPOSE: The objective of this study is to evaluate the preoperative and short- and long-term postoperative results in terms of visual acuity, refractive error, and corneal wavefront aberrations in patients with myopia and myopic astigmatism undergoing small incision lenticule extraction (SMILE). METHODS: Seventy-nine eyes of 52 myopes with or without astigmatism (41 right and 38 left) were enrolled in this retrospective study. The measurements included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), spherical equivalent (SE) and wavefront aberrations. All the measurements before and after SMILE surgery were systematically recorded. RESULTS: Mean preoperative UDVA was 1.19±0.24 logMAR and improved to 0.06±0.17 logMAR at the 3-year postoperative follow-up. At the conclusion of the 3-year follow-up, UDVA was better than or equal to 20/20 and 20/25 in 73% and 84% of eyes, respectively. At 1 month postoperatively, CDVA was 0.05±0.23 logMAR and significantly lower than the preoperative CDVA, 0.02±0.04 log MAR (P>0.05). However, at 1 year and 3 years after surgery, CDVA showed a significant increase compared to preoperative CDVA. At the conclusion of the 3-year follow-up, SE was -0.47 D, and 69.6% and 83.5% of the eyes were within±0.50 D and±1.00 D, respectively, of the intended correction. HOA's, coma, and spherical aberration increased significantly. No significant change in trefoil was detected. CONCLUSION: This study showed that SMILE produces a stable, safe outcome for surgical treatment of myopia and myopic astigmatism.

Effects of resveratrol on alpha-amanitin-induced nephrotoxicity in BALB/c mice.

Alpha-amanitin (α-AMA), the primary toxin of Amanita phalloides, is known to cause nephrotoxicity and hepatotoxicity. Resveratrol is an antioxidant that has shown efficacy in many nephrotoxicity models. The aim of this study was to investigate the effects of resveratrol against the early and late stages of α-AMA-induced nephrotoxicity, compared to those of silibinin, a well-known antidote for poisoning by α-AMA-containing mushrooms. Mice kidney tissues were obtained from five groups: (1) α-AMA + NS (simultaneous administration of α-AMA and normal saline), (2) α-AMA + SR (simultaneous administration of α-AMA and resveratrol), (3) α-AMA + 12R (resveratrol administration 12 h after α-AMA administration), (4) α-AMA + 24R (resveratrol administration 24 h after α-AMA administration), and (5) α-AMA + Sil (simultaneous administration of α-AMA and silibinin). Histomorphological and biochemical analyses were performed to evaluate kidney damage and oxidant-antioxidant status in the kidney. Scores of renal histomorphological damage decreased significantly in the early resveratrol treatment groups (α-AMA + SR and α-AMA + 12R), compared to those in the α-AMA + NS group (p < 0.05). Catalase levels increased significantly in the α-AMA + SR group, compared to those in the α-AMA + NS group (p < 0.001). Early resveratrol administration within 12 h after α-AMA ingestion may reverse the effects of α-AMA-induced nephrotoxicity, partly through its antioxidant action, thereby suggesting its potential as a treatment for poisoning by α-AMA-containing mushrooms.

Does adenosine A(1) receptor stimulation causes QRS prolongation by blocking beta adrenergic receptors in amitriptyline poisoning?

AIMS: To investigate the role of beta receptor blockade via adenosine A(1) receptor stimulation on amitriptyline-induced QRS prolongation. METHODS: Isolated rat hearts were randomized into three groups (n=8 for each group). After pretreatment with 5% dextrose (control) or DPCPX (8-cyclopentyl-1,3-dipropylxanthine), or propranolol + DPCPX, amitriptyline infusion was given to all groups. Intact beta adrenergic receptor response was verified with a bolus dose of isoproteranol (3 x 10(-5)M). RESULTS: Amitriptyline (5.5 x 10(-5)M) infusion following pretreatment with 5% dextrose or 10(-4)M DPCPX prolonged QRS by 40-110% and 30-75%, respectively. After the beta receptor blockade with 10(-2)M propranolol bolus, amitriptyline infusion following pretreatment with DPCPX prolonged QRS by 40-130%. Amitriptyline infusion following pretreatment with DPCPX (10(-4)M) shortened the QRS at 40, 50 and 60 min significantly when compared to propranolol+DPCPX group (168.8+/-4.9%, p<0.05; 170.8+/-6.9%, p<0.01; 174.0+/-6.9%, p<0.01, respectively). Amitriptyline infusion following pretreatment with 5% dextrose prolonged QRS duration significantly at 50th minutes (209.5+/-6.1%, p<0.05) compared to DPCPX pretreatment group. CONCLUSION: DPCPX pretreatment shortened amitriptyline-induced QRS prolongation. Beta adrenergic receptor blockade enhanced QRS prolongation shortened by DPCPX pretreatment. Adenosine A(1) receptor stimulation related to beta adrenergic receptor blockade may play a role in amitriptyline-induced QRS prolongation in isolated rat hearts.

Proton pump inhibitor omeprazole use is associated with low bone mineral density in maintenance haemodialysis patients.

OBJECTIVE: Limited studies have shown that proton pump inhibitor (PPI) therapy may decrease bone density or insoluble calcium reabsorption through induction of hypochlorhydria. However, PPI therapy may also reduce bone resorption via inhibition of osteoclastic vacuolar proton pumps. The aim of this study was to determine whether the opposing effects of PPI therapy may cause clinically important alterations in bone mineral densitometry (BMD) parameters in maintenance haemodialysis patients. METHODS: Sixty-eight maintenance haemodialysis patients were enrolled in this study. Patients were classified into two groups involving users of PPI therapy (omeprazole 20 mg/day, group 1, n = 36 patients) and non-users of acid suppression drugs (group 2, n = 32 patients). Patients had radius, hip and spine BMD assessed by dual-energy X-ray absorptiometry. RESULTS: The mean duration of PPI therapy with omeprazole was 27 +/- 5 months. The users of PPI therapy had lower values of bone mineral density and T-scores at the anatomical regions than non-users of acid suppression drugs. Serum calcium and phosphate levels, calcium-phosphate product and serum intact parathormone levels and the ratio of users of vitamin D therapy were similar among groups. A mutivariable adjusted odds ratio for lower bone density associated with more than 18 months of omeprazole, when all the potential confounders were considered, was 1.31 in the proximal radius, 0.982 in the femur neck, 0.939 in the trochanter and 1.192 in the lumbal spine. CONCLUSION: The present data suggest that PPI therapy should be cautiously prescribed in maintenance haemodialysis patients, especially with lower BMD values.

The analysis of interleukin-1 receptor antagonist and interleukin-1beta gene polymorphisms in Turkish FMF patients: do they predispose to secondary amyloidosis?

OBJECTIVE: Amyloid development in familial Mediterranean fever (FMF) patients is associated with acute phase response and the acute phase reactant serum amyloid A which is induced by IL-1Beta. Its concentration can increase to more than 1000 fold during inflammation. In view of the inflammatory nature of FMF disease we have investigated whether IL-1Beta and IL-1 receptor antagonist gene polymorphisms may be involved in amyloid development in FMF patients. METHODS: Ninety-nine FMF patients without amyloidosis; 54 FMF patients with amyloidosis and 60 healthy controls samples were genotyped for IL-1Beta-511 (C/T) and IL-1Beta+3953 (C/T) polymorphisms using PCR-RFLP and for IL-1Ra VNTR polymorphism using PCR. RESULTS: The allele and genotype frequencies of IL-1Beta-511 (C/T), IL-1Beta+3953 (C/T) and IL-1Ra VNTR polymorphisms in FMF patients with and without amyloidosis were all compared with those in controls. There were no significant differences between FMF patients with and without amyloidosis and healthy control samples for these polymorphisms (all P-values are >0.05). These polymorphisms were not associated with M694V mutation in FMF patients with and without amyloidosis. CONCLUSION: IL-1Beta-511 (C/T), IL-1Beta+3953 (C/T) and IL-1Ra VNTR polymorphisms are not associated with the development of amyloid in FMF patients.

Utility of the Doppler ultrasound parameter, resistive index, in renal transplant histopathology.

BACKGROUND: Doppler ultrasonography is routinely used by many clinicians during long-term follow-up to identify high-risk patients without diagnosing the exact cause of graft dysfunction. Despite a number of studies showing a correlation between intrarenal resistive index (RI) and renal function in patients with kidney diseases, correlations between RI and renal histopathologic characteristics have not been sufficiently evaluated in renal transplant recipients. The aim of this study was to examine this relationship in grafted kidneys. PATIENTS AND METHODS: The intrarenal RI was retrospectively compared with biopsy findings in 28 kidney recipients. All renal biopsy specimens were reviewed by light microscopy and immunofluorescence staining. For glomerulosclerosis, we considered the percentage of glomeruli showing this change; for interstitial fibrosis/tubular atrophy and interstitial infiltration, we graded abnormalities according to the methods of Kliem et al (Kidney Int 49:666, 1996). RESULTS: The percentage of globally sclerosed glomeruli was significantly greater among patients with RI values higher than 0.75 than below this level (23% vs 47%; P = .022). Patients with grade 1 interstitial fibrosis and tubular atrophy (n = 14) showed lower RI values (0.68 +/- 0.03 vs 0.74 +/- 0.06; P = .047) than those with grade 3 fibrosis (n = 12). Similarly, lower RI values (0.66 +/- 0.02 vs 0.73 +/- 0.05; P = .014) were observed among patients with grade 1 (n = 13) compared with grade 3 interstitial infiltration (n = 13). CONCLUSION: RI seemed to provide a prognostic marker for the graft rather than yielding an exact diagnosis of renal graft dysfunction.

Utility of c2 monitoring in prediction of diastolic dysfunction in renal transplant recipients.

BACKGROUND: A number of experimental studies have suggested that cyclosporine (CsA) toxicity induces cardiac modifications which may cause diastolic dysfunction over the course of time. Doppler echocardiography with tissue Doppler imaging (TDI) could consistently detect diastolic dysfunction. The purpose of this study was to assess diastolic dysfunction using C2 monitoring of CsA exposure in stable renal transplant patients. PATIENTS AND METHODS: Seventy-eight kidney recipients including 42 men and 36 women of overall mean age of 52 +/- 9 years were obtained in 47 living and in 31 cases from cadaveric donations over 12 or more months after transplantation using cases from CsA, mycophenolate mofetil, and steroid. C2 levels were measured by an enzyme multi-immune assay technique. The patients underwent conventional and Doppler echocardiography with TDI. RESULTS: The patients were divided into 2 groups according to C2 levels less than 500 mug/L (group 1, n = 40) versus greater than 500 mug/L (group 2, n = 38). The demographic parameters, serum creatinine and lipid levels, systolic and diastolic blood pressures, number and type of antihypertensive medications, and conventional echocardiographic parameters did not differ significantly between the groups. However, group 1 patients showed significantly higher isovolumic relaxation time (109 +/- 27 vs 86 +/- 14 ms), early diastolic deceleration time (189 +/- 52 vs 137 +/- 59 ms), and lower values of E velocity (56 +/- 32 vs 92 +/- 27 cm/s) and E/A ratios (0.81 +/- 0.23 vs 1.15 +/- 0.46) than group 2. TDI studies revealed significantly lower E'/A' (0.76 +/- 0.25 vs 1.09 +/- 0.32, P < .05) in group 1 versus group 2. CONCLUSION: The data suggested that the higher C2 levels may induce diastolic dysfunction in the hearts of kidney recipients without impairment of contractile performance.

The role of proinflammatory cytokine gene polymorphisms for development of insulin resistance after renal transplantation.

BACKGROUND: Insulin resistance, a frequent prediabetic metabolic complication after renal transplantation, is generally linked to immunosuppressive drugs including corticosteroids, cyclosporine (CsA) or tacrolimus, as well as to age, cadaveric donors and ethnic factors. Cytokines are known to be inflammation modulatory substances that contribute to metabolic derangements after transplantation. The present study investigated the effects of cytokine gene polymorphisms on insulin resistance in renal transplant recipients. PATIENTS AND METHODS: Sixty-one renal transplant recipients (37 men, 24 women; mean age: 39.3 +/- 10.8 years) who attended regular clinical visits without a known history of diabetes were enrolled in the study. All patients were on a regimen of steroid, CsA, and mycophenolate mofetil. Venous blood samples were collected for biochemical analyses after an overnight fast at 08:00 pm. CsA trough levels, C-reactive protein, and fibrinogen were also estimated. Additional 10 mL of blood was withdrawn into an ethylenediamine tetraacetic acid-containing tube to determine cytokine genotypes (tumor necrosis factor-alpha [TNF-alpha] -238 G/A, transforming growth factor-beta [TGF-beta] codon 10 -869 T/C). Insulin resistance was calculated by the homeostasis model assessment (HOMA) method using the values of fasting blood glucose (FBG) and insulin levels. Anthropometric indices as well as body height, weight, waist and hip circumferences were measured simultaneously to calculate body mass index (kg/m2) and waist-to-hip ratio. Impaired fasting glucose (IFG) was described as an FBG > or = 110 but < 126 mg/dL. RESULTS: IFG was detected in 27.9% of this study group. The HOMA index was significantly higher among patients with IFG compared with normal FBG (NoGT) (6.3 +/- 4.5 vs 3.7 +/- 1.5; P = .01). Neither FBG and insulin nor HOMA values correlated with antrophometric, metabolic, or inflammatory parameters. Cytokine genotype allele frequencies, age, sex, immunosuppressive and antihypertensive drug type and doses, CsA trough levels, and donor source (cadaveric/living) were similar for patients with IFG and NoGT. Mutant allele carrier genotypes (AA + GA) for TNF-alpha -238 G/A showed higher fasting insulin (14.0 +/- 7.9 vs 34.1 +/- 17.7 microIU/mL; P = .04) and HOMA (4.01 +/- 2.01 vs 7.95 +/- 5.44; P = .002) levels than GG homozygote subjects. FBG, HOMA, and other metabolic and anthropometric indices were similar between TGF-beta codon 10 -869 T/C genotypes. The daily dose of steroid (mg/d) and A allele frequency for TNF-alpha -238 G/A genotype were significant predictors of HOMA index in linear regression analysis. CONCLUSION: The present study revealed that beside the daily dose of steroids, TNF-alpha -238 G/A genotype may contribute to insulin resistance in renal transplant recipients. Further investigations may highlight the effects of cytokine gene heterogenity on insulin resistance in those patients.

Short and long-term impact of pharmacovigilance training on the pharmacovigilance knowledge of medical students.

OBJECTIVES: The aim of this study was to evaluate the short and long-term impact of pharmacovigilance (PV) training on the 5th year medical students' knowledge about definitions and on the awareness of the regulatory aspects in PV. MATERIALS AND METHODS: In academic year 2010/11, the students completed structured, questionnaire before and just after training. They also completed the same questionnaire 1-year after the training. RESULTS: The students' knowledge about PV significantly increased after training in the short term (P < 0.001). However, the improvement decreased significantly in the long-term (P < 0.001). Although long-term scores were higher than the baseline score, the difference was not statistically significant. Total scores were 17.5 ± 2.0, 20.8 ± 2.0 and 18.0 ± 2.5; before, at short and long-term after the training. CONCLUSION: PV training increased the students' knowledge significantly. However, in the long-term, the impact of the training is limited. Repeated training of PV should be planned.

Endothelial dysfunction in renal transplant recipients: role of vitamin D and fibroblast growth factor-23.

BACKGROUND: Endothelial dysfunction can be detected at early stages of chronic kidney disease. Although endothelial functions improve after successful renal transplantation, renal transplant recipients have still worse endothelial functions compared to healthy subjects. Vitamin D deficiency and high fibroblast growth factor-23 (FGF-23) levels may have a role on endothelial dysfunction in chronic kidney disease patients. The aim of this study is to investigate the association between endothelial functions, vitamin D, and FGF-23 levels in renal transplant recipients. METHODS: One hundred nine renal transplant recipients (71 male, 38 female) underwent brachial flow-mediated dilatation (FMD), serum 25-OH vitamin D, and FGF-23 level measurements. Vitamin D and FGF-23 levels were compared between patients with normal and abnormal endothelial functions. Correlations between FMD, vitamin D, and FGF-23 were also investigated. RESULTS: Endothelial functions were abnormal in 72.5% of the patients. Prevalence of vitamin D deficiency was 80.7%. Vitamin D levels were significantly lower in patients with endothelial dysfunction compared to patients with normal endothelial functions (12.6 ± 6.6 µg/L vs 17.3 ± 10.0 µg/L respectively, P = .02). FGF-23 levels were not different between the two groups. 25-OH vitamin D levels had a significant positive correlation with amount of FMD (r = 0.218 and P = .02) and were an independent predictor of FMD after adjusting for potential confounding factors including age, transplantation duration, body mass index, mean blood pressure, glomerular filtration rate, proteinuria, hemoglobin, and FGF-23 in multivariate regression analysis (beta = 0.194, P = .04). FGF-23 levels were not predictive of FMD in this model (beta: -0.125, P = .197) CONCLUSION: Vitamin D deficiency is associated with endothelial dysfunction in renal transplant recipients. Further clinical and experimental studies are necessary to define a causal relationship between the parameters, discover the potential mechanisms, and observe the effect of vitamin D replacement on endothelial functions in renal transplant recipients.