Histopathological changes in extraocular muscles of rabbits following injection of bupivacaine 5mg/Ml versus 7.5mg/Ml.

PURPOSE: To compare the histopathological effects of injecting two concentrations of Bupivacaine (5 mg/ml and 7.5 mg/ml) in the superior rectus muscle of rabbits, and to compare these to conventional extraocular muscle surgery in previous studies. METHODS: Eighteen albino rabbits' eyes were used. The superior rectus muscles were injected with Bupivacaine 5 mg/ml (Group B5, 10 eyes) or 7.5 mg/ml (Group B7, 8 eyes). The rabbits were sacrificed and eyes enucleated 6 weeks later for histopathological evaluation. Results were compared to the average of those obtained, by three previous studies, after conventional superior rectus resection in rabbits. RESULTS: Foreign body reaction was absent in all specimens. Conjunctival and scleral inflammation, perimuscular adhesions, intramuscular fibrosis, conjunctival and scleral oedema and muscle atrophy were higher in group B7, while conjunctival hyperaemia and muscle hypertrophy were higher in group B5 (p > 0.05). On comparison to conventional surgery, conjunctival inflammation and hyperaemia, foreign body reaction, and adhesions were less after bupivacaine injection (p > 0.05 for all except for intensity of conjunctival inflammation in B5 versus conventional surgery). Scleral inflammation was more frequent after bupivacaine injection (p < 0.05). Muscle fibrosis was more frequent in group B7 and conventional surgery than in group B5 (p > 0.05). CONCLUSIONS: Both Bupivacaine concentrations effectively produced the desired muscle hypertrophy and fibrosis, so the lower concentration may be used for muscle strengthening to correct strabismus. Bupivacaine injection, although produced no foreign body reaction, did not significantly lower the development of undesired postoperative adhesions and caused more scleral inflammation.

Metformin inhibits mTOR-HIF-1α axis and profibrogenic and inflammatory biomarkers in thioacetamide-induced hepatic tissue alterations.

The potential inhibitory effect of the antidiabetic and anti-inflammatory drug, metformin on thioacetamide (TAA)-induced hepatotoxicity associated with the inhibition of mammalian target of rapamycin (mTOR)-hypoxia-inducible factor-1α (HIF-1α) axis has not been investigated before. Therefore, we tested whether metformin can protect against liver injuries including fibrosis induced by TAA possibly via the downregulation of mTOR-HIF-1α axis and profibrogenic and inflammatory biomarkers. Rats either injected with TAA (200 mg/kg; twice a week for 8 weeks) before being killed after 10 weeks (model group) or were pretreated with metformin (200 mg/kg) daily for 2 weeks before TAA injections and continued receiving both agents until the end of the experiment, at Week 10 (protective group). Using light and electron microscopy examinations, we observed in the model group substantial damage to the hepatocytes and liver tissue such as collagen deposition, infiltration of inflammatory cells, and degenerative cellular changes with ballooned mitochondria that were substantially ameliorated by metformin. Metformin also significantly ( p < 0.05) inhibited TAA-induced HIF-1α, mTOR, the profibrogenic biomarker α-smooth muscle actin, tissue inhibitor of metalloproteinases-1, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), alanine aminotransferase (ALT) and aspartate aminotransferase in harvested liver homogenates and blood samples. In addition, a significant ( p < 0.01) positive correlation between hypoxia scoring (HIF-1α) and the serum levels of TNF-α ( r = 0.797), IL-6 ( r = 0.859), and ALT ( r = 0.760) was observed. We conclude that metformin protects against TAA-induced hepatic injuries in rats, which is associated with the inhibition of mTOR-HIF-1α axis and profibrogenic and inflammatory biomarkers; thus, may offer therapeutic potential in humans.

Accuracy of Hysteroscopic Endomyometrial Biopsy in Diagnosis of Adenomyosis.

OBJECTIVES: To investigate the diagnostic accuracy of endomyometrial biopsy obtained via office hysteroscopy for the diagnosis of adenomyosis. STUDY DESIGN: Cross-sectional study. SETTING: Cairo University Teaching Hospital, Cairo, Egypt. PATIENTS: A total of 404 premenopausal women with symptoms clinically suggestive of having adenomyosis. INTERVENTIONS: All patients were subjected to 2-dimensional transvaginal sonography (TVS) in-office hysteroscopy examination with endomyometrial biopsy. Patients who subsequently underwent hysterectomy were included in the final analysis. MAIN MEASUREMENTS AND RESULTS: Accuracy of diagnostic modalities was represented using the terms sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy. A total of 292 patients were eligible for final analysis. Of these, 162 (55.47%) were diagnosed with adenomyosis based on hysterectomy specimens. TVS had a high sensitivity (83.95%) and a moderate specificity (60%). In contrast, endomyometrial biopsy was more specific (78.46%) than sensitive (54.32%). Hysteroscopic appearance of the endometrial cavity had low sensitivity (40.74%) and specificity (44.62%). Adding endomyometrial biopsy to TVS improved specificity (89.23%). CONCLUSION: Endomyometrial biopsy obtained via office hysteroscopy can diagnose adenomyosis with a high specificity and is recommended after TVS.

The potential value of miRNA-223 as a diagnostic biomarker for Egyptian colorectal patients.

OBJECTIVES: Colorectal cancer (CRC) is the third lethal malignancy worldwide. Dysregulation of microRNAs (miRNAs) mediates several growth factors signaling pathways and induces abnormal genes expression, which leads to colorectal carcinogenesis. We aimed to comprehensively assess the expression of miRNA-200c, miRNA-203a, miRNA-223 in Egyptian CRC tissue and their corresponding serum samples and to explore if they have any potential prognostic or diagnostic value for CRC patients. METHODS: A total of 195 subjects (120 CRC patients and 75 healthy controls) participated in exploration and validation sets. The relative expression of miRNA-200c, miRNA-203a, and miRNA-223 was measured in both CRC tissue and serum samples, and the expressed miRNAs were compared in different CRC grades and types and the prognostic value was evaluated. RESULTS: The expression levels of miRNA-200c and miRNA-203a were reduced in CRC tissue samples than adjacent noncancerous tissues. miRNA-223 level was significantly upregulated in both CRC tissue and serum samples with a positive association between them (r = 0.85, P = 0.001). The miRNA-223 can effectively discriminate CRC patients from controls and can significantly differentiate between colon and rectal cancer patients. The association between serum miRNA-223 expression and CRC development was validated in the second set and the ROC curve showed highly significant prognostic value with 90.1% sensitivity, 87% specificity, and area under the curve of 0.914 (95% confidence interval: 0.830-0.978, P = 0.0001). These results showed the association between miRNA-223 upregulation and the CRC carcinogenesis. CONCLUSION: Circulating miRNA-223 can be a potential noninvasive prognostic biomarker for Egyptian CRC patients.

The Carcinogenic Agent Diethylnitrosamine Induces Early Oxidative Stress, Inflammation and Proliferation in Rat Liver, Stomach and Colon: Protective Effect of Ginger Extract.

Background: Diethylnitrosamine (DENA), a well-known dietary carcinogen, related to cancer initiation of various organs. The present study investigated the deleterious mechanisms involved in the early destructive changes of DENA in different organs namely, liver, stomach and colon and the potential protective effect of GE against these mechanisms. Methods: Adult male albino rats were assigned into four groups. A normal control group received the vehicle, another group was injected with a single necrogenic dose of DENA (200 mg/kg, i.p) on day 21. Two groups received oral GE (108 or 216 mg/kg) daily for 28 days. Sera, liver, stomach and colon were obtained 7 days after DENA injection. Serum aspartate transaminase and alanine transaminase were detected as well as reduced glutathione (GSH), malondialdehyde, nitric oxide metabolites, interleukin 1ß, tumor necrosis factor (TNF-α), alpha-fetoprotein (AFP) and nuclear factorerythroid 2-related factor2 (Nrf2) in liver, stomach and colon. Histopathological studies and immunohistochemical examination of cyclooxygenase-2 (COX2) were conducted. Results: DENA induced elevation in liver function enzymes with significant increase in oxidation and inflammation biomarkers and AFP while decreased levels of Nrf2 in liver, stomach and colon were detected. Histologically, DENA showed degenerative changes in hepatocytes and inflammatory foci. Inflammatory foci displayed increased expression of COX2 in immunohistochemical staining. GE-pretreatment improved liver function and restored normal GSH with significant mitigation of oxidative stress and inflammatory biomarkers compared to DENA-treated group. AFP was reduced by GE in both doses, while Nrf2 increased significantly. Histology and immunostaining of hepatic COX-2 were remarkably improved in GE-treated groups in a dose dependent manner. Conclusion: GE exerted a potential anti-proliferative activity against DENA in liver, stomach and colon via Nrf2 activation, whilst suppression of oxidation and inflammation.

Evaluation of therapeutic effect of low dose naltrexone in experimentally-induced Crohn's disease in rats.

BACKGROUND AND AIM: Crohn's disease is a relapsing inflammatory condition afflicting the digestive tract. Drugs used for treatment of Crohn's disease may be associated with serious side effects. Endogenous opioid peptides modulate inflammatory cytokine production. Opioid antagonists have been shown to play a role in healing and repair of tissues. This work was designed to detect the possible beneficial effects of opioid antagonist naltrexone in indomethacin-induced Crohn's disease in rats. EXPERIMENTAL APPROACH: Enteritis was induced in male albino rats by two subcutaneous injection of indomethacin in a dose of 7.5mg/kg 24h apart started on day one. Salfasalazine, naltrexone and their combination were administered orally from day one of induction of enteritis to day 10. Disease activity index, serum levels of C-reactive protein and tumor necrosis factor-α, macroscopic and microscopic pathological scores and in vitro motility studies were evaluated. RESULTS: Induction of enteritis resulted in significant increase of disease activity index, significant elevation of serum levels of C-reactive protein and tumor necrosis factor-α, significant deterioration of pathological scores and significant increase in the mean contractility response of the isolated ileal segments compared with normal untreated rats. Treatment with sulfasalazine, low dose of natrexone or their combination resulted in significant improvement of all measured parameters compared with enteritis group. CONCLUSION: The current finding could provide new interesting opportunity for developing new therapeutic approaches for treatment of Crohn's disease. Use of naltrexone, especially in small dose, has little side effects making it of interest for treatment of Crohn's disease. Also, it provides the possibility of reduced doses of other drugs if it is used as combined therapy.