Plasma and placental levels of interleukin-10, transforming growth factor-beta1, and epithelial-cadherin in preeclampsia

OBJECTIVE: To investigate the plasma and placental levels of interleukin-10 (IL-10), transforming growth factor-beta1 (TGF-beta1), and epithelial-cadherin (E-cadherin) in normotensive and preeclamptic pregnancies. METHODS: The study population consisted of 33 women with normotensive pregnancy and 35 women with preeclampsia. Peripheral venous blood samples were collected before labor (35.3 +/- 1.1 and 34.2 +/- 3.4 weeks' gestation for normotensive and preeclamptic pregnancies, respectively), and placental tissues were obtained after delivery. Maternal plasma and placental homogenate IL-10, TGF-beta1, and E-cadherin levels were determined by enzyme-linked immunosorbent assay. RESULTS: The mean plasma and placental levels of IL-10, TGF-beta1, and E-cadherin were significantly higher in preeclamptic than normotensive patients (P <.001). The plasma and placental levels of IL-10, TGF-beta1, and E-cadherin significantly increased with the increments in diastolic blood pressure (P <.001). CONCLUSION: IL-10, TGF-beta1, and E-cadherin may be involved in the pathologic process of preeclampsia. The pathophysiologic changes associated with preeclampsia may stem in part from the overproduction of these placental mediators.     

Dose-related effects of theophylline added to modified Euro-Collins solution used for hypothermic preservation of lung

OBJECTIVE: To investigate the dose-related effects of theophylline in prevention of ischemia-reperfusion injury of the lung. DESIGN: Experimental study. SETTINGS: University hospital. PARTICIPANTS: Thirty Wistar rats. INTERVENTIONS: In experimental group 1 (G-I) (n = 5) 20 mg/L, in G-II (n = 5) 100 mg/L, in G-III (n = 5) 400 mg/L, and in G-IV (n = 5) 1000 mg/L of theophylline was added to modified Euro-Collins solution and perfused the lungs. Lungs were extracted without an ischemic period in control group 1 (C-I) and perfused with modified Euro-Collins solution in control group 2 (C-II). Lungs were kept in a hypothermic state for 6 hours and then ventilated for 30 minutes with 100% O(2). MEASUREMENTS AND MAIN RESULTS: Tissue levels of dien congugate (DC) and malonylaldehyde (MDA) were measured. Comparison of 6 groups revealed statistically significant differences for DC and MDA (p < 0.0001 for both comparisons). Both DC and MDA levels of C-II were found to be higher than G-III and G-IV (p = 0.008). DC and MDA levels of G-III and G-IV were significantly lower than G-I and G-II (p = 0.008 for all comparisons). CONCLUSION: The results of this study showed that 400 mg/L and 1000 mg/L of theophylline added to the modified Euro-Collins solution decreased the intermediate products of lipid peroxidation. Theophylline merits further investigation in ischemia-reperfusion studies as a potentially beneficial agent.     

Reversible ototoxic effect of azithromycin and clarithromycin on transiently evoked otoacoustic emissions in guinea pigs

The possible cochlear toxicity of systemically applied macrolides--erythromycin (ER), azithromycin (AZ) and clarithromycin(CL)--was investigated in guinea pigs by measuring transiently evoked otoacoustic emissions (TEOAEs). A single dose of 125 mg/kg intravenous (i.v.) ER caused no change in TEOAEs in guinea pigs (p>0.05), whereas AZ (45 mg/kg orally) and CL (75 mg/kg i.v.) reversibly reduced the emission response (p<0.05). The reversible reduction of TEOAE responses due to AZ and CL, which is in accordance with the clinical picture of AZ and CL ototoxicity, could likely be attributable to the transient dysfunction of outer hair cells. The present study reveals that at least one ototoxic effect of AZ and CL is on the inner ear. The results may also encourage planning clinical researches on TEOAE monitoring in patients receiving high doses of AZ or CL.     

Scedosporium apiospermum chorioretinitis

PURPOSE: A case of a 24-year-old immunocompetent woman who developed unilateral Scedosporium apiospermum chorioretinitis and diffuse cervical lymphadenitis 10 years after facial steroid injection is described. METHODS: The patient was initially treated for the misdiagnosis of tuberculous lymphadenitis. Contemporaneous to the enlargement of her lymph nodes, she experienced gradual loss of vision in her left eye. She subsequently underwent lymph node biopsy. RESULTS: Histopathologic sections stained with Grocott's methenamine silver showed branched septate hyphae and cultures on Sabouraud's agar yielded Scedosporium apiospermum. The patient received oral itraconazole 200 mg twice daily. Lymphadenitis regressed within a year and chorioretinitis scarred within two years. CONCLUSION: Scedosporium apiospermum may cause isolated chorioretinitis in an immunocompetent individual years after local surgery or trauma and result in significant visual morbidity. Treatment may require prolonged use of systemic itraconazole.     

The sensitivity of nasal eosinophilia in allergic rhinitis

Evaluation of nasal epithelial samples is a part of clinical allergy practice. The aim of this study is to reveal the sensitivity of the nasal eosinophilia using Rhino-probe and Wright-Giemsa staining by means of all available nasal eosinophilia scoring systems. In 30 patients (12 males, 18 females; mean age = 31.6 years) with clinical diagnosis of allergic rhinitis, both sides of the nose were sampled. The content of the cupped tip of the probe has been prepared and stained for nasal cytological examination under oil immersion by light microscopy. Nasal eosinophilia has been assessed by scoring systems. The sensitivity of nasal eosinophilia has been revealed. The nasal eosinophilia scores have been compared between nasal sides (right or left nose) and also between the examiners’ observations for the same sample. Sensitivity values of nasal eosinophilia according to previously described criteria in the literature have been found to be between 13.33 and 80%. As the agreements for the nasal eosinophilia diagnosis between the sides of the nasal cavity and between the blinded examiners, the criteria of nasal eosinophilia such as the ratio of eosinophils to neutrophils or to all inflammatory cells rendered different diagnoses between the examiners (P < 0.01). The results of nasal cavity sides and Meltzer-scoring yielded no differences (P > 0.05). The substantial intraindividual variations when comparing the results obtained from the nasal sides and low sensitivity reveal that the nasal cytology needs more objective and standardized methods for a better differential diagnosis of chronic rhinitis.     

Hepatitis B core antigen expression pattern reflects the response to anti-viral treatment

BACKGROUND: In hepatitis B early antigen (HBeAg)-negative patients, response predictors to current treatment regimens are not well known. Hepatocyte cell cycle may influence hepatitis B virus (HBV) replication and hepatitis B core antigen (HBcAg) expression, which is a major target for antiviral immune response. The aim of the present paper was to evaluate the role of HBcAg expression in liver tissue and the rate of hepatocyte proliferation in response to antiviral treatment in chronic hepatitis B. METHODS: A total of 33 chronic hepatitis B patients (nine HBeAg positive, 24 HBeAg negative) treated with either lamivudine and interferon combined or lamivudine alone were included. Liver expressions of proliferating cell nuclear antigen (PCNA) and HBcAg were immunohistochemically determined. The HBV-DNA levels were measured by a hybrid capture assay. Complete response was defined as alanine aminotransferase (ALT) normalization and HBV-DNA negativity. RESULTS: At the end of treatment, 23 patients (67.7%) were responders (12 of 23 were sustained responders), while 10 (33.3%) were non-responders. Age, sex, ALT, HBV-DNA levels, HBeAg status, histological activity, fibrosis scores and PCNA labeling index were similar in responders versus non-responders at baseline. The number of patients with positive HBcAg staining was lower in responders compared to non-responders at the end of treatment (17.4% vs 80%, respectively, P < 0.001), although a similar number of sustained responders and non-responders had positive HBcAg staining. CONCLUSION: Absence or a low level of HBcAg expression may predict the end of treatment response to current therapies, especially in HBeAg (-) patients. The PCNA determination does not predict treatment response.     

The effect of flurbiprofen and tiaprofenic acid on serum cytokine levels of patients with osteoarthrosis

39 patients with active knee osteoarthrosis, chosen according to ACR criteria, were assigned to receive flurbiprofen (n 12, 2 &#50 100 mg), tiaprofenic acid (n 14, 2 &#50 300 mg) and placebo (n 13) in a 3-week, placebo-controlled study. All patients completed the study, and both medications were found to be effective: improvement occurred in the clinical signs. These drugs reduced the TNF- &#102 levels. Flurbiprofen especially affected the IL-6 levels. Our findings indicate that NSAIDs may be effective in the etiopathogenesis of osteoarthrosis.     

Synthesis,characterization, molecular docking,and biological activities of coumarin–1,2,3-triazole-acetamide hybrid derivatives

Coumarins and their derivatives are receiving increasing attention due to numerous biochemical and pharmacological applications. In this study, a series of novel coumarin–1,2,3-triazole-acetamide hybrids was tested against some metabolic enzymes including α-glycosidase (α-Gly), α-amylase (α-Amy), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), human carbonic anhydrase I (hCA I), and hCA II. The new coumarin–1,2,3-triazole-acetamide hybrids showed K_i values in the range of 483.50–1,243.04 nM against hCA I, 508.55–1,284.36 nM against hCA II, 24.85–132.85 nM against AChE, 27.17–1,104.36 nM against BChE, 590.42–1,104.36 nM against α-Gly, and 55.38–128.63 nM against α-Amy. The novel coumarin–1,2,3-triazole-acetamide hybrids had effective inhibition profiles against all tested metabolic enzymes. Also, due to the enzyme inhibitory effects of the new hybrids, they are potential drug candidates to treat diseases such as epilepsy, glaucoma, type-2 diabetes mellitus (T2DM), Alzheimer's disease (AD), and leukemia. Additionally, these inhibition effects were compared with standard enzyme inhibitors like acetazolamide (for hCA I and II), tacrine (for AChE and BChE), and acarbose (for α-Gly and α-Amy). Also, those coumarin–1,2,3-triazole-acetamide hybrids with the best inhibition score were docked into the active site of the indicated metabolic enzymes.     

Synthesis and biological evaluation of phloroglucinol derivatives possessing α‐glycosidase,acetylcholinesterase, butyrylcholinesterase,carbonic anhydrase inhibitory activity

A series of novel phloroglucinol derivatives were designed, synthesized, characterized spectroscopically and tested for their inhibitory activity against selected metabolic enzymes, including α‐glycosidase, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and human carbonic anhydrase I and II (hCA I and II). These compounds displayed nanomolar inhibition levels and showed K_i values of 1.14–3.92 nM against AChE, 0.24–1.64 nM against BChE, 6.73–51.10 nM against α‐glycosidase, 1.80–5.10 nM against hCA I, and 1.14–5.45 nM against hCA II.