Aescin Protects against Experimental Benign Prostatic Hyperplasia and Preserves Prostate Histomorphology in Rats via Suppression of Inflammatory Cytokines and COX-2.

BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common urogenital condition in aging males, while inflammation and tissue proliferation constitute the main pathophysiological factors. The adverse effects of currently available BPH medications limit patient compliance. We tested the protective effect of aescin against the development of BPH in rats. METHODS: A total of 18 male Wistar rats were divided into 3 groups: control (sesame oil 1 mL/kg, s.c.); BPH (testosterone oenanthate 3 mg/kg, s.c., in sesame oil), and BPH-aescin rats (testosterone oenanthate 3 mg/kg, s.c. + aescin 10 mg/kg/day, p.o.). All treatments continued for 4 weeks. Serum and prostatic samples were harvested for biochemical and histopathological examination. RESULTS: Induction of BPH by testosterone increased the prostate weight and prostate weight index, serum testosterone, prostate expression of inflammatory (IL-1ß, TNF-α, and COX-2), and proliferative markers (PCNA and TGF-ß1). Concurrent treatment with aescin decreased the testosterone-induced increase in prostatic IL-1ß, TNF-α, and COX-2 expression by 47.9%, 71.2%, and 64.4%, respectively. Moreover, aescin reduced the prostatic proliferation markers TGF-ß1 and PCNA by 58.3% and 71.9%, respectively, and normalized the prostate weight. CONCLUSION: The results of this study showed, for the first time, that aescin protected against the development of experimental BPH in rats via its anti-inflammatory and antiproliferative effects. These findings warrant further studies to clinically repurpose aescin in the management of BPH.

Molecular mechanisms underlying the effect of diacerein on trichloroacetic acid-induced hepatic pre-neoplastic lesions in rats.

CONCLUSION: IL-1ß mediates angiogenesis indirectly, as it has been shown to induce hypoxia-inducible factor-1α (HIF-1α) which upregulates VEGF.

Dry eye in rheumatoid arthritis: relation to disease activity.

The aim of this study was to find the correlation between severity of dry eye and rheumatoid arthritis (RA) disease activity. Forty- two RA patients with dry eye were recruited from Rheumatology Outpatient Clinic in Minia University Hospital. Assessment of RA disease activity was performed using disease activity score (DAS-28). Ocular tests include Schirmer test I, tear film break up time (TBUT) and ocular staining score (OSS) was performed by ophthalmologist to find evidence of ocular dryness. Erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), anti SSA/Ro and anti SSB/La was also tested. Patients with severe dry (OSS ≥ 3) underwent minor salivary gland biopsy (MSGB) as suspected to have secondary Sjögren's syndrome (SS). Of 42 RA patients, 30 had definite dry eye. DAS-28 did not show significant correlation with any of ocular tests for dryness while the duration of RA was significantly positively correlated with Schirmer test and OSS. The biopsy results of RA patients with severe dry eye show no evidence of SS. The severity of dry eye is not correlated with activity of RA but with its duration.

Tocilizumab attenuates acute lung and kidney injuries and improves survival in a rat model of sepsis via down-regulation of NF-κB/JNK: a possible role of P-glycoprotein.

Acute lung injury (ALI) and acute kidney injury (AKI) are major causes of sepsis-induced mortality. The objective of the study is to evaluate the effect of tocilizumab (TCZ), an IL-6 receptor inhibitor, in sepsis-induced ALI and AKI using the cecal ligation and puncture (CLP) rat model of sepsis. Clinical and experimental studies have demonstrated the importance of IL-6 in sepsis; however, the role of TCZ has not been investigated. Rats subjected to CLP developed histological evidence of ALI and AKI at 24 h. We found that TCZ alleviated sepsis-induced ALI and AKI as evidenced by improvements in various pathological changes, a significant reduction in the lung wet/dry weight ratio and total protein content in bronchoalveolar lavage fluid (BALF), and a significant decrease in the elevated serum level of creatinine (CR) and blood urea nitrogen (BUN). TCZ induced an increase in the survival rate of treated rats. Additionally, TCZ markedly inhibited sepsis-induced pulmonary and renal inflammatory responses. Moreover, we found that treatment with TCZ inhibited oxidative stress and apoptosis in lung and kidney tissue. TCZ treatment significantly inhibited NF-κB activation, attenuating JNK signaling pathway and significantly up-regulated P-glycoprotein (P-gp) expression in pulmonary as well as in renal tissues. Our data provide novel evidence that TCZ has a protective effect against sepsis-induced ALI and AKI by blocking IL-6 receptor signaling. This could provide a molecular basis for a new medical treatment for sepsis-induced ALI and AKI.

Evaluation of patients with dry eye for the presence of primary or secondary SjÓ§gren's syndrome.

PURPOSE: To assess the frequency of Sjӧgren's syndrome (SS), either primary or secondary to rheumatic disease, in a cohort of patients with aqueous-deficient dry eye and to determine the most accurate objective test for diagnosis of SS. METHODS: A total of 111 patients with dry eye were recruited from Minia University's ​Ophthalmology Outpatient Clinic (69 patients) and Rheumatology Outpatient Clinic (42 patients). The patients were screened for aqueous tear-deficient dry eye by abnormal test results of Schirmer test I (<10 mm) and tear-film break-up time (<10 seconds) in at least one eye. The diagnosis of SS was made according to the 2012 American College of Rheumatology​ criteria. A complete work up for SS was performed, including clinical examination, serological tests, ocular tests, and labial salivary-gland biopsy (LSGB). RESULTS: Of the 111 patients, 58 had aqueous-deficient dry eye: 23 in the ophthalmology clinic cohort (group I) and 35 in the rheumatology clinic cohort (group II). Three patients had pSS, and its frequency was 13% in group I and 5.2% among all studied patients. The ocular staining score is the most diagnostic ocular test (sensitivity 100% and specificity 90.9%). Anti-SSA/Ro antibody is the most accurate serological method (sensitivity 33.3% and specificity 100%). LSGB histopathology is the most diagnostic method for SS, with sensitivity, specificity, and positive and negative predictive values of 100%. CONCLUSION: SS was detected with reasonable frequency among dry-eye patients, particularly pSS. Screening of dry eye for SS can select SS patients early in the disease course.

The hepatoprotective effect of sitagliptin against hepatic ischemia reperfusion-induced injury in rats involves Nrf-2/HO-1 pathway.

BACKGROUND: Oxidative stress and inflammation play a key role in the development of hepatic ischemia reperfusion (HIR)-induced injury. Nuclear factor-erythroid 2-related factor-2 (Nrf-2) is a main regulator of numerous genes, encoding cytoprotective molecules including heme oxygenase-1 (HO-1). Sitagliptin (Sit) is an incretin enhancer acting via inhibition of dipeptidyl peptidase-4 (DPP-4) enzyme. This study was undertaken to investigate the ability of Sit to prevent the hepatic pathological changes of HIR induced injury and to modify Nrf-2 and its target HO-1. METHODS: Pringle's maneuver was used to induce total HIR in adult male rats that were randomly assigned into 4 groups. Group1 (sham-operated control), Group 2 (sham-operated + Sit-control group), Group 3 (HIR non-treated), and Group 4 (HIR + Sit). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities together with hepatic contents of malondialdhyde (MDA), nitric oxide (NO) and reduced glutathione (GSH) and superoxide dismutase (SOD) activity were evaluated. Hepatic tissue mRNA of Nrf-2 and protein content of HO-1 along with histopathological examination and scoring of hepatic injury were performed. RESULTS: Sit caused a significant reduction in ALT and AST activities together with attenuation of HIR-induced histopathological liver injury. Effect of Sit was associated with decreased hepatic level of MDA and NO with increased GSH level and SOD activity. Non-treated rats with HIR showed an increase in Nrf-2 mRNA expression and HO-1 content in hepatic tissue which was further increased by Sit treatment. CONCLUSIONS: These results indicate that hepatoprotective activity of Sit against HIR is attributed at least in part to modulation of Nrf-2/ HO-1 signaling pathway.

Ameliorative effects of silymarin on HCl-induced acute lung injury in rats; role of the Nrf-2/HO-1 pathway.

OBJECTIVES: Aspiration is a common cause of acute lung injury (ALI), which lacks an effective treatment. Inflammation and oxidative stress play key roles in ALI development. Silymarin is an active extract of Silybum marianum plant seeds (milk thistle). Silymarin has potent anti-inflammatory and antioxidant effects; however its role in aspiration induced ALI has not been investigated. The aim of this study is to investigate the role of silymarin in the treatment of hydrochloric acid (HCl) aspiration induced ALI and explores its mechanisms of action. MATERIALS AND METHODS: The study included three groups of rats: Control non-treated group, ALI group (intra-tracheal HCl injected), and silymarin treated ALI group. White blood cells (WBCs) with differential count, oxidative stress parameters, B-cell lymphoma 2 (Bcl-2), transforming growth factor-beta (TGF-ß), cyclooxygenase 2 (COX-2), nuclear factor erythroid 2-related factor-2 (Nrf-2), and heme oxygenase-1 (HO-1) were investigated. Lung tissue histopathology and immunohistochemical expression of survivin and proliferating cell nuclear antigen (PCNA) were also examined. RESULTS: The results of the study showed that HCL caused histopathological changes in ALI with leukocytopenia and increased oxidative stress biomarkers. It increased TGF-ß, up-regulated mRNA expression of COX-2, Nrf-2, and HO-1 and increased survivin and PCNA but decreased Bcl-2. Silymarin ameliorated the histopathological lung injury with further up-regulation of Nrf-2 and HO-1 mRNA and decreased the inflammatory and fibrotic parameters together with up-regulation of the anti-apoptotic and the proliferation parameters. CONCLUSION: The protective effect of silymarin against ALI is mediated by Nrf-2/HO-1 pathway with subsequent antioxidant, anti-inflammatory, antiapoptotic, and proliferating activities.

Diagnostic Utility of Twist1, Ki-67, and E-Cadherin in Diagnosing Molar Gestations and Hydropic Abortions.

OBJECTIVES: This study aims to assess whether the expression of Twist1, Ki-67, and E-cadherin can guide the differential diagnosis of complete hydatidiform mole (CHM), partial hydatidiform mole (PHM), and hydropic abortion (HA). METHODS: Differential expression of Twist1, Ki-67, and E-cadherin was analyzed in gestational products from 55 cases of CHM, PHM, and HA using immunohistochemistry. Prior to analysis, the studied cases were confirmed for their diagnosis by flow cytometric assessment of DNA ploidy and p57 immunostaining. RESULTS: Twist1 expression can distinguish CHM from PHM and HA with 100% sensitivity, 100%, specificity, 100% positive predictive value (PPV), and 100% negative predictive value (NPV). Furthermore, combined Ki-67 and E-cadherin expression could differentiate PHM and HA with 100% sensitivity, 93.3% specificity, 92.3% PPV, and 100% NPV. CONCLUSIONS: Twist1 expression is a highly reliable marker for the diagnosis of CHM, where combined Ki-67 and E-cadherin immunoreactivity can distinguish PHM from nonmolar pregnancies.