The cytotoxic concentration of rosmarinic acid increases MG132-induced cytotoxicity, proteasome inhibition, autophagy, cellular stresses, and apoptosis in HepG2 cells.

Rosmarinic acid (RA) is a natural polyphenolic compound derived from many common herbal plants. Although it is known that RA has many important biological activities, its effect on proteasome inhibitor-induced changes in cancer treatment or its effects on any experimental proteasome inhibition model is unknown. The aim of the study was to investigate the effect of RA on MG132-induced cytotoxicity, proteasome inhibition, autophagy, cellular stresses, and apoptosis in HepG2 cells. HepG2 cells were treated with 10, 100, and 1000 µM RA in the presence of MG132 for 24 h; 10 and 100 µM RA did not affect but 1000 µM RA decreased cell viability in HepG2 cells. MG132 caused a significant decrease in cell viability and phosphorylation of mammalian target of rapamycin and a significant increase in levels of polyubiquitinated protein, microtubule-associated proteins 1A/1B light chain 3B-II (LC3B-II), heat shock protein 70 (HSP70), binding immunoglobulin protein (BiP), activating transcription factor 4 (ATF4), protein carbonyl, and cleaved poly(adenosine diphosphate-ribose) polymerase 1 (PARP1); 10 and 100 µM RA did not significantly change these effects of MG132 in HepG2 cells; 1000 µM RA caused a significant decrease in cell viability and a significant increase in polyubiquitinated protein, LC3B-II, HSP70, BiP, ATF4, protein carbonyl, and cleaved PARP1 levels in MG132-treated cells. Our study showed that only 1000 µM RA increased MG132-induced cytotoxicity, proteasome inhibition, autophagy, cellular stresses, and apoptosis in HepG2 cells. According to our results, cytotoxic concentration of RA can potentiate the effects of MG132 in hepatocellular carcinoma treatment.

Effect of Lipoic Acid on Serum Paraoxonase-1 and Paraoxonase-3 Protein Levels and Activities in Diabetic Rats.

The aim of the present study was to investigate the effect of streptozotocin-induced diabetes mellitus and lipoic acid treatment on serum paraoxonase-1 and paraoxonase-3 protein levels and paraoxonase, arylesterase and lactonase activities.36 rats were equally and randomly divided into 4 groups as control, lipoic acid, diabetes and diabetes+lipoic acid. To induce diabetes, a single dose of streptozotocin (40 mg/kg) was injected intraperitoneally to diabetes and diabetes+lipoic acid groups. Lipoic acid (10 mg/kg/day) was injected intraperitoneally for 14 days to lipoic acid and diabetes+lipoic acid groups. Serum PON1 and PON3 protein levels were measured by western blotting. Serum paraoxonase, arylesterase and lactonase activities were determined by the measuring initial rate of substrate (paraoxon, phenylacetate and dihydrocoumarin) hydrolysis.Streptozotocin-induced diabetes mellitus caused a significant decrease whereas lipoic acid treatment caused a significant increase in serum PON1 and PON3 protein levels and paraoxonase, arylesterase and lactonase activities. The increase percent of serum PON3 protein was higher than that of serum PON1 protein and the increase percent of serum lactonase activity was higher than that of serum paraoxonase and arylesterase activities in diabetes+lipoic acid group.We can report that, like PON1 protein, PON3 protein and actually its lactonase activity may also have a role as an antioxidant in diabetes mellitus and lipoic acid treatment may be useful for the prevention of the atherosclerotic complications of diabetes by increasing serum PON1 and PON3 protein levels and serum enzyme activities.

The effect of lipoic acid in the prevention of myocardial infarction in diabetic rats.

OBJECTIVES: We aimed to investigate the effect of lipoic acid in the prevention of myocardial infarction in diabetic rats. METHODS: Rats were divided into five groups as control, ISO, LA+ISO, STZ+ISO and STZ+LA+ISO. To induce diabetes, single dose of streptozotocin was injected to STZ+ISO and STZ+LA+ISO groups. Lipoic acid (10 mg/kg/day) was injected for 14 days to LA+ISO and STZ+LA+ISO groups. To induce myocardial infarction, isoproterenol was injected to ISO, LA+ISO, STZ+ISO and STZ+LA+ISO groups on the days 13 and 14 of lipoic acid treatment. Cardiac necrosis and leucocyte infiltration were investigated histopathologically. Serum malondialdehyde levels, paraoxonase and lactonase activities were measured spectrophotometrically. RESULTS: Isoproterenol caused a significant increase in cardiac necrosis, leucocyte infiltration and serum lipid peroxidation whereas a significant decrease in serum paraoxonase and lactonase activities. In myocardial infarcted non-diabetic rats, while lipoic acid caused a significant decrease in cardiac necrosis, leucocyte infiltration and serum lipid peroxidation and a significant increase in serum paraoxonase and lactonase activities, it did not change these histopathologic or biochemical parameters in myocardial infarcted diabetic rats. CONCLUSION: Lipoic acid, at the dose of 10 mg/kg, is effective to prevent myocardial infarction in non-diabetic rats but it is insufficient in diabetic rats (Tab. 1, Fig. 2, Ref. 35).

The effect of anesthesia type on stress hormone response: comparison of general versus epidural anesthesia.

AIM: The aim of this study was to investigate the effect of different types of anesthesia on stress hormones. MATERIALS AND METHODS: The study was included 60 ASAI-II cases scheduled for major lower extremity surgery. The cases were randomized into 2 groups: The EA group was administered epidural anesthesia and the GA group was administered standard general anesthesia. In order to evaluate the surgical trauma - related stress response, CRP, TSH, cortisol, and fasting blood sugar(FBS) levels were measured preoperatively, 30 min after surgical incision, and 24 h post surgery. RESULTS: Between-group comparisons; Preoperative values were not significantly different between the groups.( P > 0,05) Pulse rate and cortisol values significantly higher in general group at 30 min. ( P < 0,05), and the FBS values were significantly higher in the epidural group at 24 h.( P < 0,05) There were not found differences for other parameters at evaluation times. CONCLUSION: No differences were observed between the two anesthesia methods, in terms of minimizing the stress response due to surgical trauma during major low extremity surgery.

Hypoxia-related molecules HIF-1α, CA9, and osteopontin : predictors of survival in patients with high-grade glioma.

PURPOSE: A high expression of hypoxia-inducible factor-1 alpha (HIF)-1α, carbonic anhydrase 9 (CA9), and osteopontin appears to be a strong prognostic indicator in many malignancies; however, their role is unclear in high-grade gliomas. PATIENTS AND METHODS: HIF-1α, CA9, and osteopontin levels in tissue specimens of 92 patients with high-grade glioma were evaluated by immunohistochemistry. RESULTS: Patients with a high expression of cytoplasmic and nuclear HIF-1α, CA9, and osteopontin had significantly shorter overall survival. The expression results of these markers were combined to form a hypoxic profile, and high hypoxic scores (expression of two or three markers) were significantly correlated to poorer overall survival. In multivariate analysis, high hypoxic score-1 (cytoplasmic HIF-1α, CA9, and osteopontin) was the only independent negative prognostic factor for survival (p = 0.028). CONCLUSION: Our results showed that a combination of hypoxic markers is more robust than a single marker for predicting survival in high-grade glioma. It may be necessary to utilize the hypoxic score in selecting patients for targeted therapy in the future.

Quercetin has a protective role on histopathological findings on testicular ischaemia-reperfusion injury in rats.

We investigated the effects of quercetin on pathological findings on testicular ischaemia-reperfusion (I/R) injury in rats. Twenty-four male Wistar albino rats were randomly assigned into four groups: Group 1, control (n = 5); Group 2, sham (n = 4); Group 3, I/R (n = 8); and Group 4, I/R + quercetin (n = 7). Bilateral testicular artery and vein were occluded for 1 h, followed by reperfusion in I/R and I/R + quercetin animals. Quercetin (20 mg kg(-1) per day) was administrated once daily by gavage to Group 1 and Group 4, respectively, after reperfusion. At the end of the study, bilateral orchiectomies were performed for histopathologic examination. The tissue damage was evaluated with light microscopy. Normal inter-stitium and seminiferous tubules were observed in control group. In the sham group, rats were seen minimal oedema around the seminiferous tubules and congested vascular structures. In Group 3, oedema, vascular congestion and haemorrhage between seminiferous tubules were observed. In Group 4, histopathologic features were markedly less than Group 3 (P = 0.03). Our study demonstrated that quercetin seems to have a protective effect on testis histopathology in rats with testicular I/R.

Comparison of spermatic vein histology in patients with and without varicocele.

The aim of this study was to investigate and compare histological characteristics of spermatic veins in patients with and without varicocele. Between February 2009 and July 2009, spermatic veins were obtained from 13 patients with varicocele. Microsurgical subinguinal low ligation was performed in all patients. Spermatic veins of patients without varicocele were obtained from 12 patients who underwent radical nephrectomy. Histologically, sections of veins were stained with haematoxylin and eosin. Mean tunica adventitia thickness size of the spermatic veins was 0.35 ± 0.08 mm and 0.22 ± 0.1 mm respectively in patients with varicocele and control group (P = 0.001). Similarly, mean tunica media thickness size of the spermatic veins was 0.25 ± 0.05 mm and 0.09 ± 0.04 mm respectively in patients with varicocele and control group (P < 0.001). No significant differences were detected regarding the tunica adventitia and tunica media thicknesses when patients with grade 2 varicocele were compared with patients with grade 3 varicocele (P > 0.05). No significant differences were detected between the tunica adventitia and tunica media thicknesses of patients with varicocele and sperm parameters (P > 0.05). Our study demonstrated that tunica adventitia and tunica media thicknesses seem to be increased in patients with varicocele compared with normal subjects.

Distal oesophageal pH measurement in children during general anaesthesia using the laryngeal mask airway, tracheal tube and face mask.

BACKGROUND: Distal oesophageal pH was measured during controlled ventilation in children with the laryngeal mask airway (LMATM), tracheal tube (TT) and face mask (FM). METHODS: Fifty-six children scheduled for inguinal surgery with a standardized general anaesthetic technique were randomly allocated to receive LMA (n=21), TT (n=18) or FM (n=19). A 14 Fr pH probe was placed into the distal oesophagus and pH values were measured over 1 min at 2-min intervals during the first 20 min of anaesthesia. RESULTS: The median values of pH were 4.4 (3.5-5.5), 4.2 (3.3-4.9), 4.1 (3.2-5.1), 4.1 (3.3-5.0), 4.0 (3.3-4.9), 4.0 (3.4-5.1); 4.2 (3.3-5.1), 4.2 (3.6-5.0), 4.2 (3.5-5.0), 4.2 (3.5-5.2), 4.2 (3.5-5.0), 4.1 (3.5-5.0) and 4.2 (3.6-5.0), 4.2 (3.8-5.8), 4.1 (2.8-5.2), 4.2 (3.3-5.1), 4.2 (3.4-5.1), 4.3 (3.4-5.1) for LMA, TT and FM groups, respectively. CONCLUSION: There was no difference in the median pH values, within and between the groups (P > 0.05). We conclude that there is no difference in gastro-oesophageal reflux, when using a LMA, TT or FM during controlled ventilation in anaesthetized children.