Excess adenosine in murine penile erectile tissues contributes to priapism via A2B adenosine receptor signaling

Priapism, abnormally prolonged penile erection in the absence of sexual excitation, is associated with ischemia-mediated erectile tissue damage and subsequent erectile dysfunction. It is common among males with sickle cell disease (SCD), and SCD transgenic mice are an accepted model of the disorder. Current strategies to manage priapism suffer from a poor fundamental understanding of the molecular mechanisms underlying the disorder. Here we report that mice lacking adenosine deaminase (ADA), an enzyme necessary for the breakdown of adenosine, displayed unexpected priapic activity. ADA enzyme therapy successfully corrected the priapic activity both in vivo and in vitro, suggesting that it was dependent on elevated adenosine levels. Further genetic and pharmacologic evidence demonstrated that A2B adenosine receptor-mediated (A2BR-mediated) cAMP and cGMP induction was required for elevated adenosine-induced prolonged penile erection. Finally, priapic activity in SCD transgenic mice was also caused by elevated adenosine levels and A2BR activation. Thus, we have shown that excessive adenosine accumulation in the penis contributes to priapism through increased A2BR signaling in both Ada -/- and SCD transgenic mice. These findings provide insight regarding the molecular basis of priapism and suggest that strategies to either reduce adenosine or block A2BR activation may prove beneficial in the treatment of this disorder.     

Correlation between fractional reabsorption of sodium and erythropoietin dose in peritoneal dialysis patients.

BACKGROUND: Erythropoietin (EPO) deficiency of chronic renal failure (CRF) may be a functional consequence of decreased glomerular filtration rate and fractional reabsorption of sodium (FR(Na)). Decreased FR(Na) reduces renal oxygen consumption and increases tissue oxygen pressure, resulting in less EPO production. We hypothesized that, in CRF patients, there is a positive relationship between EPO production and FR(Na) and that, in such patients receiving EPO, a negative correlation is expected between FR(Na) and EPO dose. METHODS: Creatinine clearance, FR(Na), serum iron, transferrin, transferrin saturation, ferritin, and intact parathyroid hormone (iPTH) levels were measured in 91 peritoneal dialysis patients. The correlation between EPO dose and FR(Na) was studied. RESULTS: Mean EPO dose was 7076 +/- 4821 units/week and mean FR(Na) was 93.40% +/- 6.14%. A negative correlation was found between EPO dose and FR(Na) (r = -0.28, p < 0.01), and a positive correlation was found between both ferritin and iPTH and EPO dose (r = 0.39, p < 0.001 and r = 0.35, p < 0.002 respectively). After adjusting for the effect of creatinine clearance, ferritin, and iPTH, there was still a significant correlation between EPO dose and FR(Na) (p < 0.05). CONCLUSION: In CRF patients there is a negative correlation between FR(Na) and EPO dose, which supports the hypothesis that EPO deficiency may be related to the decreased renal oxygen-consuming work of sodium reabsorption.     

The effect of intraarticular serum rich in growth factors (SRGF) on knee osteoarthritis in the rat model

Osteoarthritis (OA) is a degenerative joint disease with high incidence in world. Various treatments have been used for decreasing pain and improving physical function without clearly beneficial evidences. Nowadays, platelet-rich therapy is used as a novel approach in field of regenerative medicine. The present study evaluated the effect of intraarticular serum rich in growth factors (SRGF) on the monosodium iodoacetate induced-osteoarthritis in rat model. SRGF was injected 3 times weekly. Femorotibial joints were examined 2 weeks after last injection. Histopathologic results showed remarkable articular regeneration in the SRGF treated rats. Our findings were less surface irregularities and articular clefts, proliferation of chondrocytes and increasing synthesis of matrix proteoglycan with toluidine blue staining. Destroyed articular cartilage was repaired by fibro-hyaline cartilage in contrast to the OA rats that filled with fibrovascular tissues. The microscopic score had decreased in the treatment group. We concluded that SRGF, as a source of growth factors, have chondroinductive capacity with regard to enhancement of cartilage regeneration.     

Intestinal fungal and parasitic infections in kidney transplant recipients: a multi-center study

Kidney transplant recipients are susceptible to various infections due to the use of immunosuppressive drugs. The present study was performed as studies on the prevalence of intestinal fungal and parasitic infections in kidney transplant recipients are limited. A total of 150 kidney transplant recipients and 225 matched immunocompetent outpatients, who were referred to the laboratory of Noor Hospital, Isfahan, were studied. After recording demographic characteristics, direct test and specific laboratory cultures were carried out on the stool specimens. Patients were instructed on sanitary rules and, during each medical visit, they were reminded of the same. The overall prevalence of intestinal parasitic and fungal infections was 33.3% and 58.7%, respectively, in transplant recipients and 20% and 51%, respectively, in the control group; the difference was not statistically significant. The most prevalent intestinal parasite was Entameba coli, which was seen in 9.3% of the study patients and 6.7% of the controls. The most prevalent fungus was Candida sp., which was seen in 22% of the study patients and 24.4% of the control group. Co-existing infection with two or more fungi was seen in 14.8% and 3.4% in the case and control groups, respectively; P <0.001. Interestingly, there was no significant difference in the prevalence of infection by a single organism between the two groups. However, co-existing infection with two or more species was more prevalent in transplant recipients. We conclude that further investigations are needed to evaluate the pathogenesis of infection with these microorganisms.     

Comparing cystatin C changes as a measure of renal function before and after radiotherapy in patients with stomach cancer

The objective of this study was to determine and compare cystatin C changes before and after radiotherapy in patients with stomach cancer who were candidate for radiotherapy. This study was conducted as a prospective cohort one. Eighteen patients with definite diagnosis of stomach cancer under treatment by radiotherapy who presented to Radiotherapy-Oncology Center of Imam Hossein Hospital, Tehran-Iran, and the treatment in all cases was simultaneous chemoradiation with Xeloda were included. In all patients before radiotherapy and after radiotherapy serum creatinine (Cr) and cystatin C were measured simultaneously. Mean cystatin level before treatment (1.2 ± 0.4) was significantly lower than that of post-treatment (1.6 ± 0.36), (P=0.001). Serum Cr level before treatment was 1.15 ± 0.33 and after radiotherapy was 1.08 ± 0.24 and did not show significant difference. Glomerular filtration rate (GFR) of the patients before radiotherapy was -46.8 ± 21.0 and after radiotherapy was 43.8 ± 15.8 that did not have significant difference (P=0.146) and also blood urea nitrogen (BUN) before radiotherapy was 20.72 ± 3.7 and 20 ± 6.38 after radiotherapy that did not have significant difference (P=0.6). Comparison of the cystatin C difference with total radiation dose of the kidneys that are put in three dose groups in radiotherapy field had association that in dose of less that 18 gray (Gy) the cystatin C change showed significant and positive association (P=0.027; r=0.52) and about 18-24 Gy the cystatin C difference showed significant and negative association (P=0.023, r=-0.53). It seems that for evaluating the renal function, serum cystatin C measurement is preferable than serum Cr. level.     

Psychological insulin resistance among low-income,U.S. racial minority patients with type 2 diabetes

AimsTo examine psychological insulin resistance (PIR), the unwillingness to accept insulin therapy, within a unique U.S. population of patients with diabetes.MethodsA cross-sectional survey of PIR among low-income, U.S. Latino and African-American (AA) patients with type 2 diabetes recruited from a diabetes specialty clinic.ResultsData from 136 insulin-naïve respondents (57% female, 69% Latino, mean age 51.1 ± 10.3 years; $200–$1000 median monthly household income; grade 8–12 median education) revealed a 48% prevalence of complete unwillingness to begin insulin. In comparing Latinos to AA, Latino respondents were younger, lived fewer years in the U.S., had less education, were more likely unwilling to use insulin (53% vs. 30%, p = 0.03), and reported a more negative attitude to 8 of 9 PIR domains (p ≤ 0.01 for each). Fewer years in the U.S. predicted greater unwillingness and a more negative attitude on 8 of 9 PIR domains (p ≤ 0.03 for each); and less education predicted greater feelings of unfairness (p = 0.01).ConclusionsPIR is highly prevalent among low income, U.S. Latino patients with type 2 diabetes. Our data may help to better guide culturally appropriate counseling regarding insulin use.