Inhibitors of the Maillard reaction and AGE breakers as therapeutics for multiple diseases

The Maillard reaction is a complex series of reactions that involve reducing-sugars and proteins, giving a multitude of end-products that are known as advanced glycation end-products (AGEs). AGEs can contribute to the pathogenesis of diabetes and neurological diseases such as Alzheimer's disease. AGEs also play a major role in vascular stiffening, atherosclerosis, osteoarthritis, inflammatory arthritis and cataracts. Thus, AGE inhibitors and AGE breakers offer a potential strategy as therapeutics for diverse diseases. Various AGE inhibitors have been developed in recent years, and their underlying mechanism is based on the attenuation of glycoxidation and/or oxidative stress by the sequestration of metal ions, reactive 1,2-dicarbonyl compounds, and reactive oxygen and reactive nitrogen species.     

Effects of diazinon on pseudocholinesterase activity and haematological indices in rats: The protective role of Vitamin E

Diazinon (DZN) is an organophosphate insecticide has been used in agriculture and domestic for several years. Vitamin E (200mg/kg, twice a week), diazinon (10mg/kg, per day) and Vitamin E (200mg/kg, twice a week)+diazinon (10mg/kg, per day) combination were given to rats orally via gavage for 7 weeks. Pseudocholinesterase in serum and haematological indices were investigated at the end of the 1st, 4th and 7th weeks comparatively with control group. At the end of 1st, 4th and 7th weeks, statistically significant decrease of pseudocholinesterase activity in serum were detected when diazinon- and Vitamin E+diazinon-treated groups compared to control group. When diazinon- and Vitamin E+diazinon-treated groups were compared to each other there were no significant changes. When diazinon-treated group was compared to control group, body weight decreased significantly at the end of the 4th and 7th weeks. It was observed that at the end of 1st, 4th and 7th weeks, there was a statistically significance in haematological indices except mean corpuscular hemoglobin (MCH) when diazinon-treated group was compared to control group. At the end of 1st week increase of thrombocyte, at the end of the 4th week increase of hemoglobin and thrombocyte and at the end of the 7th week increase of red blood cell (RBC), hemoglobin, hematocrit, mean corpuscular hemoglobin concentration (MCHC) and thrombocyte were observed statistically significant when Vitamin E+diazinon treated group was compared with diazinon treated group. According to the present study, we conclude that Vitamin E reduces diazinon toxicity, but it does not protect completely.     

Erythropoietin restores bowel damage and hypoperistalsis in gastroschisis

Background and Purpose

Despite the decreased mortality in gastroschisis (Gx), patients experience postoperative intestinal hypoperistalsis, malabsorption, and shortened bowel length. The trophic effects of recombinant human erythropoietin (rEpo) in the developing small bowel have been reported, increasing the length and height of the villi, and villous surface area. This study investigated the effects of rEpo on intestinal malfunction in the chick embryos with Gx.

Methods

Thirteen-day-old fertilized chicken eggs were used to create Gx model. Study groups included the following: group 1, control; group 2, Gx-only; group 3, Gx + 0.075% saline exchange; group 4, Gx + 10 IU rEpo exchange; group 5, Gx + 20 IU rEpo exchange. The bowels were evaluated by in vitro muscle strip technique, and the response was expressed as a percentage of the maximum carbachol-evoked contraction (E_max). In addition, parasympathetic ganglion cells per 10 plexuses and villi height were determined by light microscopy. Results were evaluated statistically by Mann-Whitney U, χ², and Fisher's Exact test tests.

Results

Saline exchange had no effect on ganglion cell number (P = .63) and villi height (P = .10). In group 4, ganglion cell number was not increased (P = .82), but villi height increase was significant (P = .03). In Gx + 20 IU rEpo group, both the number of ganglia (P = .0001) and villi height (P = .002) were significantly increased. The decrease in contractility in group 2 (P = .0121) was significantly reversed by rEpo 20 IU treatment (P = .0216), no significant difference was obtained in groups 3 (P = .0809) and 4 (P = .1516) compared with group 2.

Conclusion

These data suggest that rEpo has prokinetic effects on hypoperistalsis and restores bowel damage in Gx.     

Oxygen supplementation during airway instrumentation improves intestinal barrier dysfunction

Background/Purpose

The study investigates the effect of airway instrumentation on the histopathology of the intestine, contribution of bacterial translocation, and whether oxygen supplementation may counteract the possible detrimental effects of this procedure.

Methods

Fifty-five Wistar rats were assigned to 3 groups. Group 1 served as control. Groups 2 and 3 underwent airway instrumentation. In addition, group 3 received oxygen supplementation during the procedure. Arterial blood gases were measured after the procedure. Samples of mesenteric lymph nodes ileum, cecum, spleen, liver, and blood were harvested for determination of bacterial growth after 24 hours. Ileum was evaluated histologically.

Results

In group 2, the rats presented a decrease in oxygen saturation (90% ± 0.3%, P < .0001), hypoxemia (Pao₂, 73 ± 1.5 mm Hg; P < .0001), and respiratory acidosis (pH 7.27 ± 0.01; Paco₂, 48 ± 1.5 mm Hg; P < .0001) after airway instrumentation. These rats also showed evidence of intestinal injury (P < .0001) and bacterial translocation to mesenteric lymph nodes in 10 of 20 rats compared with 0 of 15 in the controls (P = .004). In group 3, oxygen supplementation provided normal arterial blood gas parameters, and led to minimal histologic changes and bacterial translocation in only 1 of 20 rats, compared with group 2 (P < .0001 and P = .005, respectively).

Conclusions

The study suggests that oxygen supplementation during airway instrumentation prevents hypoxemia, intestinal damage, and bacterial translocation.     

Mid-course thoracic radiotherapy with cisplatin-etoposide chemotherapy in limited-stage small-cell lung cancer

Combination chemoradiotherapy is a standard treatment for limited-stage small-cell lung cancer (LS-SCLC). However, there is still controversery about the optimal timing of thoracic radiotherapy (TRT). In this study, the outcome of 70 patients who had received TRT at a dose of median 50 Gy (range, 46–60 Gy) with a second or third cycle of chemotherapy (CHT) either concurrently (n=41) or sequentially (n=29) were analyzed retrospectively. All patients were administered a median of five cycles (range, four to six cycles) cisplatin plus etoposide (EP) CHT. Prophylactic cranial radiotherapy was delivered to 30 (43%) patients. The median follow-up for all patients was 15 mo (range, 6–60 mo). The median overall survival was 19 mo in the concurrent arm vs 15 mo in the sequential arm. The 2-yr local control, disease-free survival, and overall survival rates were 60%, 19%, and 36%, respectively. The most common toxicity was esophagitis. However, there were no grade 3–4 esophagitis in either arm. Grade 3–4 hematologic toxicity, on the other hand, appeared significantly more in the concurrent arm (p<0.001). Mid-course of once-daily TRT at a moderate total dose with CHT failed to show any improvement in survival. Additionally, there were no differences between concurrent and sequential CHT with TRT. However, acceptable toxicity rates support the use of once-daily fractionation to higher total dose of TRT.     

Expression of steroid receptors in intact rat uterus, mammary gland, and liver treated with selective estrogen receptor modulators and conjugated equine estrogens

The aim of the present study was to determine the effects of conjugated equine estrogens (CEE) and selective estrogen receptor modulators (SERM) (tamoxifen [TAM] and raloxifene [RAL]) on the expression of steroid receptors—estrogen receptor (ER) and progesterone receptor (PR)—in intact rat uterus, mammary gland, and liver. A total of 24 female rats weighing 250 to 300 g were randomized into 4 groups. Groups 1, 2, 3, and 4 were respectively given conjugated equine estrogen, tamoxifen, raloxifene, and vehicle for a 28-day period. ER and PR expression was detected in tissues of the uterus, mammary gland, and liver. Uterine wet weight and serum estradiol levels were established for all groups. No statistical difference was observed between groups in the ER expression of mammary gland and liver and in the PR expression of uterus, mammary gland, and liver, but differences were noted in serum estradiol levels and uterine ER expression. Serum estradiol levels were lower in the TAM-treated group; differences between the TAM-treated group and the other groups were statistically important (P > .05). Uterine ER expression was greater in the CEE-treated group; differences between the CEE-treated group and theTAM and RAL-treated groups were statistically important (P > .05). CEE or SERM versus vehicle treatment in controls did not seem to result in statistically important differences in ER and PR expression in intact rat uterus, mammary gland, and liver. Only ER expression in the uterus was found to be greater in the CEE-treated group than in SERM-treated groups.     

The effects of Islam and traditional practices on women's health and reproduction

The aim of this study was to investigate the effects of Islam as a religion and culture on Turkish women's health. The study included 138 household members residing in the territory of three primary health care centers in Turkey: Güzelbah?e, Fahrettin Altay and Esentepe. Data were collected by means of a questionnaire prepared by a multidisciplinary team that included specialists from the departments of public health, psychiatric nursing and sociology. We found that the women's health behavior changed from traditional to rational as education levels increased, and that religious and traditional attitudes and behaviors were predominant in the countryside, especially practices related to pregnancy, delivery, the postpartum period, induced abortion and family planning. One of the most important prerequisites for the improvement of women's health is that nurses should know the religious practices and culture of the society for which they provide care, so that their efforts to protect and improve women's health will be effective.     

A case of microglandular adenocarcinoma of the endometrium

BACKGROUND: Microglandular adenocarcinoma is a rare type of endometrium carcinoma and had some potential diagnostic problems with difficulties in discriminating from some malign and benign lesions of cervix. CASE REPORT: A 70-year-old woman misdiagnosed as cervical adenocarcinoma was referred to our clinic, and the lesion was ultimately evaluated as microglandular adenocarcinoma in repeat of endometrial curettage specimen. Postoperatively, histopathologic examination of specimen revealed grade 1 microglandular adenocarcinoma. To our best knowledge, this is the twelfth case of uterine carcinoma simulating microglandular hyperplasia in the literature. CONCLUSION: Because microglandular adenocarcinoma can be confused with benign lesions like microglandular hyperplasia and malignant lesions of cervix, we aim to discuss the clinical, demographic and immunohistochemical characteristics of the patients with microglandular adenocarcinoma useful in differential diagnosis.     

Bilateral primary orbital non-Hodgkin's lymphoma in a patient with scleroderma: a case report

Orbital presentation of non-Hodgkin's Lymphoma (NHL) is uncommon but occurs both as the only site of disease and as a site of recurrence. Primary orbital NHLs are usually low-grade, and mostly extranodal marginal zone/mucosa associated lymphoid tissue B-cell neoplasms. They are commonly associated with chronic inflammatory conditions. The issue of bilaterality in orbital lymphoma is not very common. The onset of malignant lymphoproliferation may precede, follow, or exist simultaneously with scleroderma. Different treatment modalities were applied in orbital NHL such as surgery, radiation therapy, chemotherapy or both. We report a 57-year-old man with scleroderma presenting with eyelid hernias who had biopsy-proven marginal zone NHL, successfully treated with radiotherapy and combined chemotherapy, and also review the literature.     

Liver transplant length of stay (LOS) index: A novel predictive score for hospital length of stay following liver transplantation

An index to predict hospital length of stay after liver transplantation could address unmet clinical needs. Length of stay is an important surrogate for hospital costs and efforts to limit stays can preserve our healthcare resources. Here, we devised a scoring system that predicts hospital length of stay following liver transplantation. We used univariate and multivariate analyses on 73 635 adult liver transplant recipient data and identified independent recipient and donor risk factors for prolonged hospital stay (>30 days). Multiple imputation was used to account for missing variables. We identified 22 factors as significant predictors of prolonged hospital stay, including the most significant risk factors: intensive care unit (ICU) admission (OR 1.75, CI 1.58‐1.95) and previous transplant (OR 1.60, CI 1.47‐1.75). The length of stay (LOS) index assigns weighted risk points to each significant factor in a scoring system to predict prolonged hospital stay after liver transplantation with a c‐statistic of 0.75. The LOS index demonstrated good discrimination across the entire population, dividing the cohort into tertiles, which had odds ratios of 2.25 (CI 2.06‐2.46) and 7.90 (7.29‐8.56) for prolonged hospital stay (>30 days). The LOS index utilizes 22 significant donor and recipient factors to accurately predict hospital length of stay following liver transplantation. The index further demonstrates the basis for a clear clinical recommendation to mitigate risk of long hospitalization by minimizing cold ischemia time.