Hepatoprotective Effect of Mixture of Dipropyl Polysulfides in Concanavalin A-Induced Hepatitis

The main biologically active components of plants belonging to the genus Allium, responsible for their biological activities, including anti-inflammatory, antioxidant and immunomodulatory, are organosulfur compounds. The aim of this study was to synthetize the mixture of dipropyl polysulfides (DPPS) and to test their biological activity in acute hepatitis. C57BL/6 mice were administered orally with DPPS 6 h before intravenous injection of Concanavalin A (ConA). Liver inflammation, necrosis and hepatocytes apoptosis were determined by histological analyses. Cytokines in liver tissue were determined by ELISA, expression of adhesive molecules and enzymes by RT PCR, while liver mononuclear cells were analyzed by flow cytometry. DPPS pretreatment significantly attenuated liver inflammation and injury, as evidenced by biochemical and histopathological observations. In DPPS-pretreated mice, messenger RNA levels of adhesion molecules and NADPH oxidase complex were significantly reduced, while the expression of SOD enzymes was enhanced. DPPS pretreatment decreased protein level of inflammatory cytokines and increased percentage of T regulatory cells in the livers of ConA mice. DPPS showed hepatoprotective effects in ConA-induced hepatitis, characterized by attenuation of inflammation and affection of Th17/Treg balance in favor of T regulatory cells and implicating potential therapeutic usage of DPPS mixture in inflammatory liver diseases.     

Risk factors for nipple involvement in breast cancer patients

Introduction: A clinically normal‐appearing nipple in patients with breast cancer may contain unsuspected neoplastic cells. Preservation of a nipple containing occult malignancy could potentially increase local recurrence rates and affect disease‐free survival. Consequently, patients considered for breast conservation operations with nipple preservation must be carefully selected. Methods: Information available on 382 patients diagnosed and treated with breast cancer at the Clinical Center Nis from 2000 to 2003 were retrospectively reviewed. Multivariate hazard analyses was used to assess the association between potential risk factors of cancerous nipple involvement. Results: The frequency of nipple involvement was 12.04%. Nearly half of the patients had disease stage III and IV. Most patients, 29 (63.04%), had a tumor to nipple distance of less then 2 cm. Twenty‐five patients (54.34%) had more then four positive axillary nodes. A central/overlap tumor location was present in 28 (60.87%) patients. Cox multivariate analysis of prognostic factors showed that Stage III (RH 4.79 (1.50–14.68, 1.50–14.72); P= 0.008), central/overlap tumor location (RH 3.28 (0.90–11.20); P= 0.078) and nuclear grade III or greater (RH 2.26 (0.79 to 6.65); P= 0.065) had a statistically significant effect on malign nipple involvement. Conclusions: The multivariable model used in this study showed a significant association between stage, centrally located tumors and nuclear grade III or greater in predicting the risk of cancerous nipple involvement. Preoperative magnetic resonance imaging or computed tomography scan examinations are recommended for treatment planning of breast cancer, in particular nipple preserving surgery in patients with central/overlap tumor localization and with a tumor to nipple distance of less than 2 cm.     

The luteinizing hormone receptor-activated extracellularly regulated kinase-1/2 cascade stimulates epiregulin release from granulosa cells

We examine the pathways involved in the luteinizing hormone receptor (LHR)-dependent activation of the epidermal growth factor (EGF) network using cocultures of LHR-positive granulosa cells and LHR-negative test cells expressing an EGF receptor (EGFR)-green fluorescent protein fusion protein. Activation of the LHR in granulosa cells results in the release of EGF-like growth factors that are detected by measuring the phosphorylation of the EGFR-green fluorescent protein expressed only in the LHR-negative test cells. Using neutralizing antibodies and real-time PCR, we identified epiregulin as the main EGF-like growth factor produced upon activation of the LHR expressed in immature rat granulosa cells, and we show that exclusive inhibition or activation of the ERK1/2 cascade in granulosa cells prevents or enhances epiregulin release, respectively, with little or no effect on epiregulin expression. These results show that the LHR-stimulated ERK1/2 pathway stimulates epiregulin release.     

Effect of adding albumin to solutions of somatostatin on inhibiting pentagastrin-stimulated acid secretion in dogs

In five conscious dogs with chronic gastric fistulas we studied the effect of somatostatin solutions on pentagastrin-stimulated acid secretion. Somatostatin was dissolved in 0.154 M NaCl alone or in the same amount of saline to which dog albumin had been added to give a 0.5% solution. Somatostatin produced a dose-dependent inhibition of pentagastrin-stimulated gastric secretion. However, the inhibition was significantly less when somatostatin was dissolved in saline as compared to saline plus albumin. This study suggests that albumin should be added to somatostatin solutions to preserve biological activity, and it confirms previous reports indicating that, without albumin, basic peptides have a tendency to stick to infusion systems.     

Fetal and maternal plasma homocysteine levels during the second half of uncomplicated pregnancy

Objective: To measure fetal and maternal plasma homocysteine (Hcy) concentrations in uncomplicated pregnancies.

Methods: Paired maternal venous and fetal umbilical cord blood (n?=?81) samples were evaluated for plasma Hcy and vitamin B₁₂ levels, in addition to eight neonatal umbilical cord blood samples obtained immediately following delivery.

Results: Both fetal and maternal Hcy concentrations were positively correlated with advancing gestational age (ρ?=?0.44, p?<?0.0001; and ρ?=?0.27, p?<?0.05, respectively). Fetal plasma Hcy concentrations [2.2?µmol/l (IQR: 2.0–3.2)] were significantly lower than both neonatal umbilical vein [5.0?µmol/l (IQR: 4.4–6.5); p?<?0.001] and maternal plasma Hcy levels [4.4?μmo/l (IQR: 3.4–5.4); p?<?0.001]. In addition, Hcy values at term were higher in the umbilical vein compared with the umbilical artery [5.0?μmol/l (IQR: 3.4–5.4) versus 4.2?μmol/l (IQR: 3.7–5.5), respectively; p?=?0.016]. Significant correlation was noted and between fetal and maternal Hcy levels (ρ?=?0.50, p?<?0.0001), while fetal Hcy was negatively correlated with maternal B₁₂ concentrations (ρ?=??0.32, p?<?0.001).

Conclusions: Fetal Hcy levels were significantly lower than maternal and neonatal levels and correlated with gestational age across the second half of pregnancy.