Background Ulcerative colitis (UC) is a chronic inflammatory disease of large intestine. Overproduction of free radicals, lowered antioxidant capacity and abnormal apoptosis are involved in pathogenesis. Nebivolol, a β blocker with vasodilatory, antioxidant, anti-inflammatory effects, can play future role in therapies for UC. Aim of the study The purpose of this study was to evaluate the protective effect of nebivolol against acetic acid (AA)-induced UC in rats. Methods Male wistar rats were pre-treated orally with nebivolol 5 mg/kg/d, 10 mg/kg/day, for seven days, before and 3 days after induction of colitis (by intra-rectal administration of 2 ml of 4% AA). Colonic macroscopic scoring and histopathological examination were done. Colonic content of thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD) and myeloperoxidase (MPO) activities were assessed. Apoptosis was monitored by determining caspase-3 gene expression. Serum levels of interleukin (IL)1-β, SOD, TBARS and tumour necrosis factor (TNF)-α were measured. Results In AA- group, serum levels of TBARS, TNF-α and IL-1β were significantly increased. SOD activity was significantly reduced. Caspase 3 protein expression was upregulated. Colonic content of TBARS and the activity of MPO were elevated. GSH concentration and activity of SOD were significantly reduced, compared to control group. In nebivolol pretreated groups (5 and 10 mg/kg/d) and sulfasalazine group, all parameters were near normal. Nebivolol significantly decreased colonic macroscopic scoring and wet colon weight compared to AA group. The coloprotective effect of nebivolol was confirmed by histopathological examination. Conclusion Nebivolol has a protective effect against AA- induced colitis, through its anti-inflammatory, anti-oxidant and anti-apoptotic effects.

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Rationale Multiple cranial nerve palsies can be a feature of infective, inflammatory and neoplastic processes. It is very important to differentiate between these conditions as the treatment is completely different. In the case that we are reporting, meningeal biopsy helped in revealing the diagnosis. Case Summary A 64 year old man presented with headache for 6 weeks, facial weakness for 3 weeks and swelling of the right eye with inability to move the right eye for 1 week. Our initial impression was cavernous sinus thrombosis, but the MRI brain did not show thrombosis of the cavernous sinus. Moreover there was thickening of the meninges on the MRI. As the patient had a history of myositis and pulmonary fibrosis and he had remained on steroids, we considered a septic or an autoimmune process. We empirically started steroids and antibiotics and the patient started to improve. However, to establish a diagnosis, we decided to go for a meningeal biopsy. It showed granulomatous inflammation and staining for infections and malignancies was negative. Considering his history of autoimmune disease and pulmonary fibrosis, we diagnosed him as a case of neurosarcoidosis and gave him high dose steroids and the patient improved. Conclusion Meningeal biopsy is helpful in establishing the diagnosis and to differential between infectious, inflammatory and neoplastic processes.

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Background Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system of unknown reason or definite cure, heavily impacting the patient's mobility and overall quality of life. Purpose Through this study the authors propose safe, alternative phototherapies for the early management of MS. Study design This is a repeated-measures randomized control trial. Materials and methods Twenty-four patients with relapsing remitting MS, of both sexes, aged 25–45 years, completed the study; they were randomly assigned to four groups. Seven patients in the control group (group 1) received monthly intravenous infusion of 1 g solu-medrol therapy for MS; six patients in group 2 received solu-medrol plus low-intensity laser therapy (LILT) at 850 nm; six patients in group 3 received solu-medrol plus broadband ultraviolet B radiation (BB-UVBR) (280–320 nm); five patients in group 4 received solu-medrol and scanner LILT and BB-UVBR. All three groups received a total of 12 sessions over a period of 3 days/week. Expanded disability status scale (EDSS) and H-reflex latency were assessed before treatment, after treatment, and at 3 months’ follow-up. Results There was statistically significant reduction (P = 0.009∗∗) in H-reflex latency but not in H/M ratio (P ≥ 0.05) in the LILT group (group 2), whereas EDSS was significantly reduced (P = 0.011∗) by 1 point in the BB-UVBR group (group 3). These results were maintained 3 months after treatment. Conclusion This study suggests that LILT can efficiently reduce spasticity in the short term in patients with relapsing remitting MS. While BB-UVBR therapy alone is more efficient in ameliorating the disability status (EDSS), and combining LILT with UVBR, surprisingly, might have an undermining effect.

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Objective The aim of this study was to evaluate the role of Cerebrolysin in muscle healing in vivo. Materials and methods Twenty adult albino rats were used in this study. Both right and left gastrocnemius muscles of the albino rats were cut at 60% of their length from their distal insertion through 75% of their width and 50% of their thickness and then sutured with simple sutures using absorbable catgut sutures. The gastrocnemius muscles of all albino rats were injected directly in the lesion with 100 ng/ml/kg of cerebrolysin at 1, 3, and 5 days after laceration. The sham control muscles were subjected to the same treatment but were injected with the same volume of physiological normal saline. One week after the injury the animals were killed and the gastrocnemius muscles were removed and processed for paraffin sectioning and stained with hematoxylin and eosin, Bcl-2 (B-cell lymphoma 2), and P53 (tumor suppressor gene) immune peroxidase stains. Results There was a significant increase in the mean myonuclei/myofiber diameter ratio and the size of the regenerating myofibers as an index of muscle regeneration in the cerebrolysin-injected group compared with the control. It is anticipated that cerebrolysin is a potent stimulator of muscle regeneration in vivo. It has also been found that regenerating myofibers were located both in the deep and the superficial areas of the injured site of muscles only when treated with cerebrolysin, thereby demonstrating greater initial healing when the injured muscle is treated with cerebrolysin. Cerebrolysin retarded apoptosis in neutrophils, macrophages, and other inflammatory cells by activating the anti-apoptotic Bcl-2 (B-cell lymphoma 2) protein leading to accumulation of these inflammatory cells. Conclusion This study has shown that injections of cerebrolysin into an injured muscle improved muscle healing in vivo. Also, documents the occurrence of a protective Bcl-2 in inflammatory neutrophils and macrophages, which were expressed in cerebrolysin-treated muscles, leading to enhancement of the effect of these inflammatory cells. We have also found that Inflammatory cells play a role in satellite cell activation and proliferation but, the tumor suppressor gene p53, which is recognized as a central regulator of cell cycle and apoptosis, had no role in muscle regeneration in this in-vivo study.

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Background Worldwide, breast cancer is the most common cancer in women. Currently, Bmi1 has been linked to a stem cell-like 11 gene expression microarray signature, predictive of tumor relapse, metastasis, and resistance to therapy in multiple human cancers. Aim The aim of this study was to evaluate immunohistochemical expression of Bmi1 in invasive breast cancer, and its correlation with the clinicopathological features, hormone receptor status [estrogen receptor (ER) and progesterone receptor (PR)], HER2/neu score, Ki67 proliferation index, and molecular subtypes. Patients and methods Fifty invasive breast carcinomas were studied for immunohistochemical demonstration of Bmi1, ER, PR, HER2/neu, and Ki67. Cases were classified into four molecular subtypes (luminal A, luminal B, Her2-enriched, and triple negative). Results Bmi1 expression was detected in 37 (74%) breast carcinoma cases, and a significant positive association with tumor size (P=0.03) and lymph node metastasis (P=0.01) was reported in this study. No significant correlation was detected between Bmi1 expression and other variables such as age, histologic type, grade, hormone receptor status, Her2 status, Ki67, and molecular subtypes (P>0.05). Conclusion Bmi1 stem cell marker was detected in a high percentage of breast cancer cells, and there was a significant positive association with tumor size and lymph node metastasis, which confirms its role in aggressiveness and dissemination of cancer cells. However, no correlations with ER, PR, Her2, Ki67 expressions, or molecular subtyping were found. Further studies are required to rule out the prognostic value of cancer stem cell marker Bmi1 and its therapeutic targeting.

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Background and objectives The colorectum is the segment of the gastrointestinal tract most frequently affected by tumors. Most colonic tumors are benign epithelial polyps. There are many histologic types of polyps. The best characterized and most common cancer precursor is the adenomatous polyp. The size, number of adenomas, grade of dysplasia, and villous features predict the future risk for advanced neoplasia, including malignancy in patients who harbor adenomas. A number of studies have been published studies evaluating the clinical use of cyclin D1 immunohistochemical (IHC) expression as a predictor of malignant transformation in colorectal adenomas. The aim of the study was to evaluate the significance of IHC expression of cyclin D1 in colorectal adenomas as a marker for the prediction of malignant transformation. Patients and methods This study is a retrospective one in which a total of 39 formalin-fixed paraffin-embedded polypectomy specimens from patients with colorectal adenomas without concurrent or previous colorectal adenocarcinoma were retrieved from the archival materials during the period from March 2013 to March 2014. The histopathological diagnosis had been revised and all specimens were stained using IHC technique with cyclin D1. Results IHC expression of cyclin D1 had a significant correlation with villous type (P=0.003) and high-grade dysplasia in adenomas (P=0.021). However, there was no significant difference in the IHC expression of cyclin D1 according to the age and sex of the patients, and the size and site of colorectal adenomas (P>0.05). Conclusion Cyclin D1 potentially contributes to the multistep process of colorectal oncogenesis. It plays an important role in the malignant conversion of colorectal adenomas, as it is more likely to be expressed in advanced adenoma with high-grade dysplasia and villous histology and can be used as an ancillary marker for the risk for malignant transformation and as a target for chemoprevention with anti-inflammatory drugs.

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Objective The aim of this study was to evaluate copeptin as a predictor of short-term ICU mortality in patients with sepsis and its relation with disease severity. Design This study was an observational case–control one. Methods The study included 60 patients admitted to the ICU with sepsis: 20 patients with sepsis, 20 patients with severe sepsis, and 20 patients with septic shock. Baseline characteristics, serum copeptin, and APACHE II score were determined at the time of admission. They were prospectively followed up for 7 days to determine improvement, development of multiple organ failure, or death. Copeptin level in patients with sepsis was compared with its level in the control group comprising 10 patients with congestive heart failure, 10 patients with post-acute myocardial infarction, and 10 healthy individuals. Results The mean copeptin level was 48.4 (15.1) pmol/l in patients with sepsis, 69.2 (15.4) pmol/l in severe sepsis, and 120.9 (31.2) pmol/l in septic shock. It was significantly higher than its level in post-acute myocardial infarction [21.1 (8.0) pmol/l], congestive heart failure [20.6 (9.8) pmol/l], and healthy controls [8 (4.3) pmol/l] (P<0.001). Spearman correlation analysis showed a positive correlation between copeptin and total leukocytic count (r=0.466; P<0.001), urea (r=0.496; P<0.001), creatinine (r=0.552; P<0.001), alanine aminotransferase (r=0.451; P<0.001), and APACHII (r=0.661; P<0.001). Improved patients significantly had lower copeptin [43.5 (8.7) pmol/l] than those who died [103.8 (36.2) pmol/l] (P<0.001). Area under the curve of copeptin for predicting mortality was 0.880 (P<0.001). A cutoff value of 58.1 pmol/l had 96.6% sensitivity and 61.3% specificity. Conclusion Serum copeptin is a sensitive predictor of mortality in critically ill patients with sepsis. Moreover, it could be a promising biomarker for disease severity and development of multiple organ failure in this group of patients.

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Background Torsion of the ovary is a gynecologic emergency syndrome, which has a vital role in the development of ovarian ischemia. The major aim of ischemia treatment is to recover tissue perfusion. However, ischemia–reperfusion (I/R) injury is associated with reactive oxygen species production. The aim of our work was to study the possible histological and biochemical changes due to I/R injury in rat ovaries and the probable protective effect of zafirlukast as an anti-inflammatory and antioxidant agent. Materials and methods Twenty-four adult female Wister albino rats were distributed into three groups: group I, the control group; group II, in which the rats were subjected to 3 h of ischemia followed by 1 h of reperfusion; and group III, in which the rats were subjected to 3 h of ischemia followed by zafirlukast administration (20 mg/kg, orally) and then 1 h of reperfusion. Groups II and III were divided into two smaller groups from which the ovaries were surgically removed either after 4 h or after 2 weeks of starting the experiment. Levels of malondialdehyde, glutathione, tumor necrosis factor α, and nitric oxide were determined, and histopathological changes were examined. Results Vascular congestion, hemorrhage, edema, increased caspase-3 immunoreaction, a rise in malondialdehyde, nitric oxide, and tumor necrosis factor α levels, and a decrease in reduced glutathione level were observed in the ovaries after I/R, which improved with zafirlukast administration, especially after 2 weeks. Conclusion Zafirlukast reduces the severity of ovarian I/R injury, probably through anti-inflammatory action and suppressing oxidative stress.

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Background Irisin, an exercise-induced myokine, has broad implications for metabolism and energy homeostasis. The aim of this work was to investigate the irisin expression and its receptor and the signaling pathway in relation to cognitive functions to allow for a better understanding of its role in an exercised diabetic model. Materials and methods A total of 40 adult male albino rats were divided equally into four groups. The first group included control rats (the control group). The remaining animals were used to establish a type 2 diabetic model and were further divided into the following: the diabetic sedentary group; the chronic exercised diabetic group; and the acute exercised diabetic group. At the end of the study period, the behavioral assessment was carried out for all groups in a T-maze. After scarification, gastrocnemius muscles, whole brains, and abdominal adipose tissues were excised for the measurement of gene expression of muscle irisin, brain irisin receptors, brain-derived neurotrophic factor (BDNF), brain MAPK and adipose tissue uncoupling protein 1 (UCP1), and MAPK. In addition, insulin sensitivity indices and serum lipid profile were measured for the studied groups. Results Muscle irisin expression was significantly elevated in chronic and acute exercised diabetic rats (P < 0.001) compared with diabetic sedentary rats. Significant positive correlations existed between the muscle irisin mRNA expression patterns compared with the brain irisin receptors expression, BDNF, brain MAPK (r = 0.878, 0.933, and 0.908, respectively; P < 0.001 for all), as well as cognitive performance together with an improvement in insulin sensitivity and lipid profile. On the other hand, although muscle irisin was correlated positively with adipose MAPK, it was negatively correlated with UCP1. Conclusion Our results suggest that raised muscle irisin levels for both types of exercise are involved in the improvement of cognitive functions and insulin sensitivity in diabetic rats. However, further studies should clarify its precise role in relation to fat browning.

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Context The worldwide increase in the prevalence of laryngeal cancer is a major health problem. Human papilloma virus (HPV) infection is a major cause for laryngeal carcinoma, especially in nonsmokers. Aim This study investigated the effect of HPV on laryngeal carcinoma prognosis and whether HPV-associated carcinoma cases carry a better or worse outcome. This was approached by studying the relationship between HPV infection (indicated by p16 immunoreactivity) and various prognostic markers of laryngeal carcinoma such as patients’ age, tumor grade, lymph node metastasis, thyroid cartilage infiltration, and immunohistochemical markers of tumor proliferation such as cyclin D1 and p53. Materials and methods This was a preliminary study that included paraffin blocks of 40 cases of laryngeal squamous cell carcinoma, obtained either as laryngoscopic biopsies or laryngectomy samples with or without selective neck dissection. All cases were immunostained using antibodies against p16, cyclin D1, and p53. Statistical analysis The clinical, histopathological, and immunohistochemical data are summarized as percentages and means±SD. The χ²-test was used to assess differences between qualitative variables, whereas the t-test and analysis of variance were used for quantitative variables. A P-value less than 0.05 was considered to be significant. Results A statistically significant correlation was observed between p16 expression and tumor grade, lymph node metastasis, thyroid cartilage infiltration, and immunoexpressions of cyclin D1 and p53. No other prognostic markers correlated with p16 expression. Conclusion HPV-induced squamous cell carcinoma may carry a worse prognosis in the larynx.

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