Investigation of the Factors Affecting Allograft Kidney Functions: Results of 10 Years

IntroductionSignificant improvements in patient and graft survival and reductions in the frequency of acute rejection were obtained in the early period after renal transplantation, but this success was not sufficiently reflected in the long term. Allograft kidney losses in the long term remain a significant problem. In this study, we investigated the specific causes of graft losses in patients who had a good clinical course in the first year but developed graft loss in the long term.MethodsA total of 118 patients who underwent kidney transplantation in 2005 and 2006 in the Organ Transplantation Center of Ege University Medical Faculty Hospital were evaluated. The inclusion criteria were to be older than 18 years and have a serum creatinine value of <2 mg/dL at the 12th month after transplantation.ResultsSixty-one percent of the recipients were male, and the mean age at the time of transplantation was 34 ± 11 years (18 to 61). We observed 29 graft losses during the mean follow-up period of 129 ± 35 months (27 to 162). Three of the graft losses were death by functional graft. Of the 26 patients with graft loss, 16 had chronic rejection, and 8 had recurrent glomerulonephritis. The relationship between nonimmune causes and graft loss was not detected.ConclusionsIn conclusion, nonimmune factors may not be as important as we think in relatively young and healthier recipients. Chronic rejection and recurrent glomerulonephritis are the main causes of long-term graft loss of patients with good graft function at the end of the first year. Improvement of long-term survival will be possible with the prevention and effective treatment of these 2 problems.     

Mucormycosis Presented with Facial Pain in a Renal Transplant Patient: A Case Report

IntroductionMucormycosis is a severe infection in renal transplant recipients. Here, we report a case of maxillary sinus mucormycosis in a patient who presented with a facial pain complaint.CaseA 51-year-old female patient with renal transplantation due to autosomal dominant, polycystic kidney disease and diabetic nephropathy was admitted to our hospital with facial pain and minimal edema of the left half of her face on the 8th month of transplantation. On physical examination, there was only tenderness and slight edema on the left half of the face. On the paranasal computed tomography, extensive soft tissue densities involving septations, filling the left maxillary sinus, extending to the nasal cavity, and obliterating the left osteometeal unit were observed. Because facial pain was not relieved by antibiotics and several, potent analgesic drugs on the second day, mucormycosis infection with bone involvement was suspected. A left maxillary sinus excision was performed. Microscopic examination of the debridement specimen revealed necrotic bone interspersed with fungal hyphae, and culture isolated Rhizopus oryzae. Liposomal amphotericin B was started. The patient was on tacrolimus, prednisolone, and mycophenolate mofetil. Tacrolimus was switched to cyclosporine to regulate serum glucose levels. The left maxillary sinus was washed with liposomal amphoterin B daily and curetted with intervals. The patient started dialysis because of severe renal function loss. The patient was discharged on the 96th day of liposomal amphotericin B.ConclusionIt should be kept in mind that mucormycosis may be present in the sinuses even if there is no evidence for nasal, oral, and dental examination in renal transplant patients with facial pain.     

Hydrogen sulphide inhibits carbachol-induced contractile responses in β-escin permeabilized guinea-pig taenia caecum

Hydrogen sulphide (H(2)S) is an endogenous mediator producing a potent relaxation response in vascular and non-vascular smooth muscles. While ATP-sensitive potassium channels are mainly involved in this relaxant effect in vascular smooth muscle, the mechanism in other smooth muscles has not been revealed yet. In the present study, we investigated how H(2)S relaxes non-vascular smooth muscle by using intact and β-escin permeabilized guinea-pig taenia caecum. In intact tissues, concentration-dependent relaxation response to H(2)S donor NaHS in carbachol-precontracted preparations did not change in the presence of a K(ATP) channel blocker glibenclamide, adenylate cyclase inhibitor SQ-22536, guanylate cyclase inhibitor ODQ, protein kinase A inhibitor KT-5720, protein kinase C inhibitor H-7, tetrodotoxin, apamin/charybdotoxin, NOS inhibitor L-NAME and cyclooxygenase inhibitor indomethacin. We then studied how H(2)S affected carbachol- or Ca(2+)-induced contractions in permeabilized tissues. When Ca(2+) was clamped to a constant value (pCa6), a further contraction could be elicited by carbachol that was decreased by NaHS. This decrease in contraction was reversed by catalase but not by superoxide dismutase or N-acetyl cysteine. The sarcoplasmic reticulum Ca(2+)-ATPase pump inhibitor, cyclopiazonic acid, also decreased the carbachol-induced contraction that was further inhibited by NaHS. Mitochondrial proton pump inhibitor carbonyl cyanide p-trifluromethoxyphenylhydrazone also decreased the carbachol-induced contraction but this was not additionally changed by NaHS. The carbachol-induced Ca(2+) sensitization, calcium concentration-response curves, IP(3)- and caffeine-induced contractions were not affected by NaHS. In conclusion, we propose that hydrogen peroxide and mitochondria may have a role in H(2)S-induced relaxation response in taenia caecum.     

Effects of sertraline on behavioral alterations caused by environmental enrichment and social isolation

Environmental conditions are known to play a critical role in the pathogenesis of affective disorders. In this study, the effects of sertraline, a selective serotonin (5-HT) reuptake inhibitor, on anxiety- and depression-like behaviors were investigated in rats reared in different housing conditions. Wistar rats of both sexes were divided into three groups according to their rearing conditions (Enriched = EC, Isolated = IC and Standard = SC), after weaning at postnatal day 21. While animals in control conditions were housed as a group of 4 rats in regular size plexiglass cages, social isolation groups were housed individually in metal cages. Animals in enriched conditions were housed as a group of 12 rats in specially designed cages equipped with different stimulating objects. Six weeks later, activitymeter, elevated plus maze, rotarod, grip, forced swimming and sucrose preference tests were applied to all animals and all of the tests were repeated after i.p. injection of sertraline (10 mg/kg/day) for 7 days. Environmental enrichment reduced the stereotypic behavior, improved the motor coordination and facilitated the learning skills in animals. However, housing conditions affected depression-like parameters, but not anxiety-like parameters. Sertraline treatment reduced the depression-like effect in EC and SC, but not in IC. It decreased anxiety-like behavior in IC while increased in EC. Socially isolated animals preferentially consumed more sucrose and water than the other groups, and interestingly, these differences became more significant following sertraline treatment. These results show that the responses of animals to anti-depressive drugs could be differentially affected by the behavioral consequences of the diverse housing conditions. Thus, to improve the treatment of depression; behavioral consequences of diverse housing conditions should be taken into consideration.     

IL-1β is induced in reactive astrocytes in the somatosensory cortex of rats with genetic absence epilepsy at the onset of spike-and-wave discharges, and contributes to their occurrence

Interleukin (IL)-1β plays a crucial role in the mechanisms of limbic seizures in rodent models of temporal lobe epilepsy. We addressed whether activation of the IL-1β signaling occurs in rats with genetic absence epilepsy (GAERS) during the development of spike-and-wave discharges (SWDs). Moreover, we studied whether inhibition of IL-1β biosynthesis in GAERS could affect SWD activity.IL-1β expression and glia activation were studied by immunocytochemistry in the forebrain of GAERS at postnatal days (PN)14, PN20, and PN90 and in age-matched non-epileptic control Wistar rats. In PN14 GAERS, when no SWDs have developed yet, IL-1β immunostaining was undetectable, and astrocytes and microglia showed a resting phenotype similar to control Wistar rats. In 3 out of 9 PN20 GAERS, IL-1β was observed in activated astrocytes of the somatosensory cortex; the cytokine expression was associated with the occurrence of immature-type of SWDs. In all adult PN90 GAERS, when mature SWDs are established, IL-1β was observed in reactive astrocytes of the somatosensory cortex but not in adjacent cortical areas or in extra-cortical regions.An age-dependent c-fos activation was found in the somatosensory cortex of GAERS with maximal levels reached in PN90 rats; c-fos was also induced in some thalamic nuclei in PN20 and PN90 GAERS.Inhibition of IL-1β biosynthesis in PN90 GAERS by 4-day systemic administration of a specific ICE/Caspase-1 blocker, significantly reduced both SWD number and duration.These results show that IL-1β is induced in reactive astrocytes of the somatosensory cortex of GAERS at the onset of SWDs. IL-1β has pro-ictogenic properties in this model, and thus it may play a contributing role in the mechanisms underlying the occurrence of absence seizures.     

Lipid peroxidation, DNA damage and coenzyme Q10 in lung cancer patients--markers for risk assessment?

Objectives: Early diagnosis and prevention is very important for lung cancer patients. Previous studies have emphasized that the level of coenzyme Q10 (CoQ10), present primarily in mitochondria, decreases with age and is low in patients with chronic diseases. Our goal was to find out if there is any relationship between lung cancerand CoQ10 and lipid peroxidation levels. Design and Methods: Blood samples from lung cancer patients were collected. Total and oxide CoQ10 levels, 8-OHdG (product of DNA damage), and malondialdehyde (MDA) levels (lipid peroxidation) were analyzed with high performance liquid chromatography (HPLC). Results: The MDAlevel (P<0.001) and DNA damage rate (8-OHdG) (P<0.001) was higher in cancer patients than in the control group; in contrast, theCoQ10 enzyme level was ignificantly lower (P<0.001). Conclusion: The results suggest t hat the aforementioned parameters can be useful for lung cancer risk assessment.     

Factors determining students’ global satisfaction with clerkships: an analysis of a two year students’ ratings database

Clerkships would benefit from teachers’ improved understanding of the didactic aspects of their task. The purpose of this study is to identify factors that determine the teaching quality of clerkships and to examine the predictive value of these factors for students’ global satisfaction. Thus, results would be further reflected to clinical teachers’ tasks. These factors could then be taken into account in future clinical teaching. In this paper, a medical faculty’s 2 year data set of student feedback from a systematic programme evaluation project was used. A factor analysis was performed on 11,780 student questionnaires. Factor loads, and the Cronbach’s alpha coefficients of the questionnaire and factors were calculated. In order to examine the contributions of the factors to the students’ global satisfaction, the study included a multivariate stepwise regression analysis. The analysis revealed four factors, which together explained 60.24% of the variance: Structure & Process (44.66%); Time (5.8 %); Outcome (5.35%) and Input (4.39%). The Structure & Process factor was found to be the best predictor of students’ global satisfaction (R ² = .537). Our conclusion is that “efforts to improve clerkship quality should focus on students’ learning processes and clerkship structure”.     

Presence of obestatin in breast milk: relationship among obestatin, ghrelin, and leptin in lactating women

OBJECTIVE: The peptide hormones ghrelin and leptin have been found in blood and breast milk. This study was undertaken to investigate whether breast milk also contains obestatin, which is derived from the same gene as ghrelin but has opposite actions, and to characterize the relations among serum and milk ghrelin, obestatin, and leptin levels in lactating mothers. METHODS: Venous blood, colostrum, and mature milk were obtained from healthy lactating women (n = 31) just before suckling. The ghrelin and obestatin concentrations were determined by radioimmunoassay. Leptin levels were measured by enzyme-amplified sensitivity immunoassay. RESULTS: Obestatin levels in colostrum (538.9 pg/mL) and mature milk (528.5 pg/mL) were more than twice the corresponding blood levels (270.3 and 289.4 pg/mL, respectively). In contrast, leptin levels in colostrum (2.01 ng/mL) and mature milk (2.04 ng/mL) were more than five-fold lower than the corresponding blood levels (11.54 ng/mL). There was no correlation between breast milk ghrelin levels and leptin (r = -0.18, P > 0.05). However, there was a positive correlation between leptin levels in breast milk and blood (r = 0.369, P < 0.05). CONCLUSION: The origin of milk obestatin is not currently known, but it comes from the blood or breast and may drain through the mammary glands into the milk. Ghrelin, obestatin, and leptin in the milk may directly affect appetite and their levels may be related to the regulation of energy balance and the pathogenesis of obesity.