The effects of specific and non-specific phosphodiesterase inhibitors and N-acetylcysteine on oxidative stress and remote organ injury in two-hit trauma model.

BACKGROUND: Sepsis is a systemic inflammatory response to infection and is one of the leading causes of morbidity and mortality. The second hit after trauma causes increased inflammatory response and multiple organ failure (MOF). The infection which develops after burn injury is a suitable model for a two-hit trauma study. Sepsis causes the release of biochemical mediators, such as Free Oxygen Radicals (FORs), which may lead to lipid peroxidation, which may play a key role in multiple organ failure. In this study, we aimed to investigate the effects of phosphodiesterase (PDE) inhibitors (sildenafil, milrinone, pentoxifylline) and N-acetylcysteine (NAS) on oxidative stress and organ damage in two-hit models. METHODS: In this experimental study, peritonitis was created by cecal ligation and puncture (CLP) method in 40 rats, 72 hours after creating a 30% scalding injury. Rats were divided into five groups of eight rats each as follows: Group I: No treatment; Group II: 10/mg/kg/day dosage of intraperitoneal (i.p) sildenafil treatment was applied for 72 hours after CLP; Group III: 1/mg/kg/day dosage of i.p milrinone treatment was applied for 72 hours after CLP; Group IV: 150/mg/kg/day dosage of i.p NAS treatment was applied for 72 hours after CLP; Group V: 50/mg/kg/day dosage of i.p pentoxifylline treatment was applied for 72 hours after CLP. All rats were sacrificed on the seventh day of this study. Malondialdehyde (MDA), Glutathione Peroxidase (GPx), Superoxide Dismutase (SOD), catalase, Tumor Necrotic Factor-alpha (TNF-α) levels, and tissue (lung, kidney) and serum samples were taken for histopathological study. RESULTS: When compared to the control group, the tissue damage score was found to be lower in all treatment groups. Sildenafil, milrinone and NAS groups had higher kidney GPx levels compared to the control group. Milrinone and pentoxifylline were higher in the lung tissue compared to the SOD control group. TNFα levels were lower in pentoxifylline and milrinone groups compared to the control group. CONCLUSION: This experimental study has shown that PDE inhibitors and NAS have a decreasing effect on oxidative stress and distant organ damage in the two-hit model. Further clinical and experimental studies are needed on this subject.

Visible-Light-Driven Tunable Molecular Motors Based on Oxindole.

Molecular rotary motors based on oxindole which can be driven by visible light are presented. This novel class of motors can be easily synthesized via a Knoevenagel condensation, and the choice of different upper halves allows for the facile tuning of their rotational speed. The four-step rotational cycle was explored using DFT calculations, and the expected photochemical and thermal isomerization behavior was confirmed by NMR, UV/vis, and CD spectroscopy. These oxindole motors offer attractive prospects for functional materials responsive to light.

Methylenetetrahydrofolate reductase gene germ-line C677T and A1298C SNPs are associated with colorectal cancer risk in the Turkish population.

Colorectal cancer (CRC) is the third most common cause of death due to cancer in the worldwide and the incidence is also increasing in Turkey. Our present aim was to investigate any association between germ-line methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and CRC risk in Turkey. A total of 86 CRC cases and 212 control individuals of the same ethnicity were included in the current study. Peripheral blood-DNA samples were used for genotyping by StripAssay technique, based on the reverse- hybridization principle and real-time PCR methods. Results were compared in Pearson Chi-square and multiple logistic regression models. The MTHFR 677TT (homozygous) genotype was found in 20.9% and the T allele frequency 4.2-fold increased in CRC when compared with the control group.The second SNP MTHFR 1298CC (homozygous) genotype was found in 14.0% and the C allele frequency 1.4-fold elevated in the CRC group. The current data suggest strong associations between both SNPs of germ-line MTHFR 677 C>T and 1298 A>C genotypes and CRC susceptibility in the Turkish population. Now the results need to be confirmed with a larger sample size.

Antitumoral effects of Allium sivasicum on breast cancer in vitro and in vivo.

This work aims to investigate the antiproliferative properties of Allium sivasicum (AS) on breast cancer. AS extracts were studied for cytotoxicity against the breast cancer cell lines. In vitro apoptosis studies of breast cancer cells were performed by annexin V staining in flow cytometry analyses. AS showed cytotoxicity to three cancer cell lines. Annexin-positive cells level in AS treated cell lines were higher than the untreated control cells. The expressions of caspase-7 protein and TUNEL positive cells were much higher for the rats treated by AS, compared with the untreated control group. The expressions of the Ki-67 decreased in treatment groups compared with the control group. In vivo studies showed that mean tumor volume inhibition ratio in AS treated group was 38 % compared with the untreated rats. These results indicate that A. sivasicum has antitumoral potential against breast cancer.

The impact of Ramadan on peptic ulcer perforation.

BACKGROUND: Medical treatment has played an important role in the reduction of peptic ulcer perforation (PUP). The goal of this study was to evaluate the effect of fasting on PUP. METHODS: A retrospective analysis of 229 patients who were operated due to PUP between 1999-2009 was made. Patients were divided into two groups. Group I (n=188) included the patients who were operated in other periods of the year, while Group II (n=41) included the patients who were operated during Ramadan, the Muslim period of fasting. Patients in Group II were analyzed in terms of duration of fasting. RESULTS: The increase in surgeries per group was higher in Group II than Group I (p<0.05). Predisposing factors, anti-ulcer drug usage and demographic variables were seen to have no role in this difference. Duration of fasting may have a minimal effect on the perforation. CONCLUSION: The results of this study demonstrate that PUP is detected as relatively higher during Ramadan among those who are fasting for more than 12 hours daily. We suggest that people with predisposing factors should be informed before making a decision to fast.

Antitumoral effects of Melissa officinalis on breast cancer in vitro and in vivo.

BACKGROUND: There is a long standing interest in the identification of medicinal plants and derived natural products for developing cancer therapeutics. Here we investigated the antiproliferative properties of Melissa officinalis (MO) from Turkey on breast cancer. METHODS: MO extracts were studied for cytotoxicity against breast cancer cell lines (MCF-7, MDA-MB-468 and MDA-MB-231). In vitro apoptosis studies were performed by annexin V staining and flow cytometry analyses. Immunohistochemistry for Ki-67 and caspase 7 in the tumoral tissue sections of DMBA-induced mammary tumors in rats was also performed, along with TUNEL assays to detect apoptotic cells. In vivo anticancer activity testing was carried out with reference to inhibition of growth of DMBA induced mammary tumors in rats. RESULTS: MO showed cytotoxicity against three cancer cell lines, inducing increase in Annexin-positive cells. Expression of caspase-7 protein and TUNEL positive cells were much higher in rats treated by MO, compared with the untreated control group, while expression of Ki-67 was decreased. Furthermore, in vivo studies showed that mean tumor volume inhibition ratio in MO treated group was 40% compared with the untreated rats. CONCLUSION: These results indicated that MO extrcts have antitumoral potential against breast cancer.

A new technique for partial splenectomy with radiofrequency technology.

The advantage of partial splenectomy is the preservation of its immunologic function. In this series, 8 patients underwent a spleen preservation procedure with radiofrequency. Four of the partial splenectomy procedures were performed in elective situations, whereas the other 4 cases were performed to control traumatic bleeding in emergency situations. A harrow-like radiofrequency probe with 6 needles was applied to the spleen, and the division of the splenic parenchyma was completed using a surgical scalpel through the midline of the ablated tissue. This safe, fast, and simple technique allows for preservation of splenic function with minimum blood loss.

Small bowel tumors in emergency surgery.

BACKGROUND: The aim of the present study was to describe the clinical presentation, diagnostic work-up, surgical therapy, and prognosis of 13 patients with small bowel tumor admitted for surgical procedures in an emergency setting. METHODS: From 1996 to 2008, 13 consecutive surgical cases of small bowel tumors were treated at the Cumhuriyet University Faculty of Medicine, Department of General Surgery, and Kütahya State Hospital, Department of General Surgery. Clinical and radiological charts of these patients were reviewed retrospectively from the department database. RESULTS: Intestinal obstruction (7 cases) and perforation (5 cases) were the most common clinical presentations, followed by intussusception (1 case). Adenocarcinoma was the most frequent histologic type (4 cases), while small bowel sarcoma was seen in three cases and non-Hodgkin lymphoma in two cases. The remaining cases had carcinoid tumor, small bowel angioleiomyoma, Brunner's gland adenoma, and inflammatory pseudotumor of the small intestine. CONCLUSION: Small bowel tumors are rare, the symptoms often non-specific, and the accuracy of different diagnostic tests remains to be improved. Timing and type of the intervention to the process and biological behavior of the pathological cells predict the prognosis.

Epigenetic inactivation of tumor suppressor SFRP2 and point mutation in KRAS proto-oncogene in fistula-associated mucinous type anal adenocarcinoma: report of two cases.

The secreted frizzled-related proteins (SFRPs) genes are unmethylated in normal colorectal mucosa tissue but aberrant methylation profiles can be detected in colorectal cancer (CRC), adenomas, and in aberrant crypt foci. The aim of the current study was to clarify whether SFRP2 methylation and K-ras structural mutation in fecal DNA can be found in stool and tumoral tissues of individuals with fistula-associated mucinous type anal adenocarcinomas (MTAA).Two man patients (68 and 56 years old) were treated for anorectal fistula in the surgical department. Patients were evaluated for clinical findings, tumoural tissue samples were examined histopathologically and DNA from fecal and tumoral tissue samples were isolated. K-ras mutation and promoter hypermethylation of SFRP2 gene in tumoral tissues were assessed by methylation-specific PCR based stripAssay hybridisation technique (Me-PCR) and compared to the healthy controls. Fecal and tumoural tissue samples from both patients were found to be fully hypermethylated profiles for SFRP2 gene and combined point mutations were detected in codon 12 and 13 of K-ras proto-oncogene. The current results showed that the combined effects of somatic mutations in K-ras and epigenetic alterations in SFRP2 genes may play an active role in the development of mucinous type anal adenocarcinoma.

Cardiac functions evaluated with tissue Doppler imaging in childhood cancers treated with anthracyclines.

AIM: The aim of this study was to assess the cardiac functions using conventional echocardiography and tissue Doppler imaging in childhood cancers treated with anthracyclines. METHODS: The study group was selected from the patients admitted to the pediatric oncology department for a treatment protocol that included doxorubicin. Body surface area was calculated and complete 2-dimensional, M-mode, pulse wave Doppler and pulse wave tissue Doppler echocardiographic examinations were performed just before the first treatment and at least 6 months after the last treatment. RESULTS: This study included 20 patients (12 males and 8 females). Mean cumulative antracycline dose was 189 +/- 102.90 mg/m(2). There were no significant differences between the pre- and post-treatment groups regarding systolic and diastolic blood pressures, heart rates, left ventricular ejection fraction and fractional shortening, right and left ventricular conventional and tissue Doppler diastolic parameters (E and A waves, E/A ratio, E' and A' waves, E'/A' ratio), but there were significant differences between the pre- and post-treatment groups regarding body surface area, right and left ventricular myocardial performance index observed by conventional pulse wave and pulse wave tissue Doppler methods. CONCLUSION: Tissue Doppler imaging provided additional information on cardiac functions. While systolic and diastolic functions were in normal range, myocardial performance index observed by tissue Doppler method was impaired in children who were treated with anthracyclines.

Neurofibroma adjacent to the thyroid gland and a thyroid papillary carcinoma in a patient with neurofibromatosis type 1: report of a case.

Neurofibromatosis (NF) type 1, also known as von Recklinghausen's disease, is an autosomal-dominant inherited disorder. Some tumors may develop in these patients, including optic pathway gliomas, astrocytomas, brainstem gliomas, chronic myeloid leukemia, and rhabdomyosarcoma. Patients with neurofibromatosis type 1 show also an increased risk of endocrine tumors, especially pheochromocytomas, whereas thyroid carcinoma is very rare. It is also rare for a neurofibroma to arise in the tissue neighboring the thyroid gland, and mimicking a nonfunctional thyroid nodule. This report presents a case of a neurofibroma adherent to the thyroid gland with thyroid papillary carcinoma in a 26-year-old woman with NF type 1.

Surgical management strategies in patients with primary hyperparathyroidism: which technique in which patients?

OBJECTIVE: This study was planned to investigate the efficacy of either 99mTc-sestamibi scan or ultrasonography in predicting the operative treatment in patients with primary hyperparathyroidism (PHPT). SUBJECTS AND METHOD: Thirty patients (25 female, 5 male; mean age: 53 years) being operated for symptomatic primary PHPT were included in this study. Ultrasonography was used in 29 patients while 99mTc-sestamibi scintigraphy was done in 28 patients to localize the hyperfunctioning gland(s). Standard bilateral neck exploration was done in 6 patients. Although unilateral intervention had been planned for 24 patients, bilateral intervention was performed in 9 of them. RESULTS: Sensitivity of 99mTc-sestamibi was 81%, while that of ultrasonography was 42%. 99mTc-sestamibi localization method led to misleading results in 10/28 (35.7%) patients. False-positive localization and accompanying thyroid pathologies played an important role in determining transition from unilateral to bilateral intervention. CONCLUSION: Our findings indicate that bilateral intervention remains a successful management option without prior localization in patients with PHPT especially in an endemic goiter region.

Chlorhexidine gluconate: an ideal scolicidal agent in the treatment of intraperitoneal hydatidosis?

Hydatid disease is a parasitic disease that is treated primarily by surgery. The most important complication of surgical treatment is spillage of the contents of the cyst, leading to secondary dissemination. In this study, the effect of chlorhexidine gluconate (Chx-Glu) was investigated in the treatment of experimental intraperitoneal hydatidosis (IPH). IPH was reproduced in 100 Wistar albino rats by inoculation with 1 ml of a suspension contained approximately 1500 viable protoscolices of Echinococcus granulosus following determination of scolicidal activity of chlorhexidine gluconate in vitro. Five minutes after protoscolex inoculation, 5 ml of the scolicidal solution was instilled into the peritoneal cavity: 0.9% NaCl (control group), 4.0% Chx-Glu, 0.4% Chx-Glu, and 0.04% Chx-Glu. After 6 months of follow-up, the rats were sacrificed, and the number of isolated cysts, peroperative and postoperative deaths, and toxicity were evaluated. Cyst formation did not occur in any of the Chx-Glu groups compared to the control group (p < 0.05), whereas it was detected in all of the control rats. In addition, to 4.0% Chx-Glu was found to be more toxic and to cause a high mortality rate compared to the 0.4% and 0.04% Chx-Glu groups and the control group (p < 0.05). Chx-Glu 0.04% was found to be the most potent, nontoxic agent; it is easily available, inexpensive, and highly potent in a short period of time at the low concentration. Chx-Glu 0.04% can be used safely in the treatment of intraperitoneal hydatidosis and hydatid cyst.

Do vascular endothelial growth factor and basic fibroblast growth factor promote phenytoin's wound healing effect in rat? An immunohistochemical and histopathologic study.

BACKGROUND: This study was designed to determine the possible correlation between phenytoin and vascular endothelial growth factor and basic fibroblast growth factor in the wound healing process. METHODS: Sixty Wistar albino rats were divided into four groups, each containing 15 animals. The experimental groups received a daily phenytoin treatment (10 mg) for 3 or 7 days following 3-cm dorsal skin incisions on the midline; the control group incisions were treated with 0.5 mL of saline solution during the same time periods. After completion of treatments, all animals were killed, and skin tissue samples were obtained. RESULTS: Histopathologic examination of all groups revealed that there were significantly increased (p<0.05) amounts of fibroblasts, collagen deposition, and blood vessels in the phenytoin-treated groups when compared to the control groups. Although immunolocalization of vascular endothelial growth factor and basic fibroblast growth factor was weak in the 3-day phenytoin treatment groups, they were strongly expressed in the 7-day treatment group when compared to the control groups. CONCLUSION: The findings of this study demonstrate that the tissue alterations of the wound healing process could be accelerated by phenytoin and the potential local pathways of vascular endothelial growth factor and basic fibroblast growth factor.

A functioning-desensitization paraganglioma which caused hemodynamic instability during tumoral resection: report of a case.

Paragangliomas are uncommon tumors arising from the neuroendocrine elements of the paraganglia. Their successful management is associated with many problems. We herein present the findings of a 22-year-old man in whom a paraganglioma was incidentally found and in which the clinical and previous operative behavior was functioning desensitization. As a result, preoperative medication was not performed; however, during the tumor resection the patient demonstrated hemodynamic instability.

Could prolactin receptor gene polymorphism play a role in pathogenesis of breast carcinoma?

OBJECTIVE: Constitutive activation of various hormone and growth factor receptors is newly recognised as a common cause of tumour development. This study investigated the presence of any mutation or polymorphism of prolactin receptor (PRLR) in 38 patients with breast cancer. RESEARCH METHODS: Genomic DNA was extracted and PCR amplification was carried out for exon 1-10 of PRLR from tumoral and adjacent non-cancerous breast tissue of tumour specimens from 38 breast cancer patients. PCR products were analysed by SSCP and automatic sequencing for mutations. RESULTS: For the first time, A150C (Leu-->Ile) transversion at exon 6 of PRLR in tumour tissues, in adjacent non-cancerous breast tissues, and in blood samples of two (5.3%) out of 38 patients with breast cancer were detected. In contrast to this finding, no polymorphism of PRLR in blood samples of 100 normal individuals were found. CONCLUSION: Polymorphism of prolactin receptors might play a role in mammary carcinogenesis as a consequence of intracellular changes of PRLR signalling.

Altered contractile responsiveness in ileal longitudinal muscle after total gastrectomy in a rat model.

PURPOSE: To test the hypothesis that the changes in ileal smooth muscle contractility accompanying postgastrectomy syndromes are agonist-specific, we investigated the effects of potassium chloride (KCl), carbachol, substance P (SP), and serotonin on ileal smooth muscle contractility after total gastrectomy in rats. METHODS: We performed total gastrectomy in ten rats and a sham operation in another ten rats as a control. All of the rats were killed and their ileums excised 4 weeks postoperatively. The concentration-response relationships for KCl, SP, and serotonin were obtained by adding each agent cumulatively to the organ bath. Morphological changes in the ileum were also examined by light microscopy. RESULTS: There was no significant difference between the responsiveness of gastrectomized and control tissues to KCl. Maximum responses (E(max)) to carbachol and SP were less in the gastrectomized ileal segments than in the control ileal segments. E(max) to serotonin was higher in the gastrectomized ileal segments than in the control ileal segments. The pD(2)value, i.e., the negative logarithm of the concentration for the half-maximal response, EC(50), for carbachol, SP, and serotonin was unchanged in the gastroctomized ileal segments and the control segments. Total gastrectomy also caused morphological changes in the ileum. CONCLUSIONS: These data indicate that the contractile response to various agents is altered after total gastrectomy and that receptor-mediated mechanisms may cause these changes.

Positive effects of phenytoin on experimental colonic anastomoses.

BACKGROUND AND AIMS: Anastomotic dehiscence following colorectal surgery is a significant cause of morbidity and mortality. Phenytoin has wound-healing promoting and collagenase inhibitory effects. This study assessed these effects on healing of experimental colonic anastomoses in a rat model. MATERIALS AND METHODS: Ninety Wistar rats weighing 240-290 g were divided into six groups: 3rd-day control group (n=15), 3rd-day oral administration of phenytoin (n=15), 3rd-day rectal administration of phenytoin (n=15), 7th-day control group (n=15), 7th-day oral administration of phenytoin (n=15), and 7th-day rectal administration of phenytoin (n=15). In oral phenytoin groups the agent was given at 10 mg/kg daily per orogastric route by 4-F fine feeding catheter; in rectal phenytoin RAP groups the agent was administered at 10 mg/0.5 cc daily to the anastomoses transrectally via a fine anal catheter. RESULTS: There were significantly higher anastomosis bursting pressure values and hydroxyproline contents in phenytoin groups than in controls. In histopathological examination it was seen that phenytoin treatment caused greater collagen deposition, fibroblast, and blood vessel ingrowth than in controls. Immunohistochemical analysis showed the stimulatory effect of phenytoin in expression of vascular endothelial growth factor and basic fibroblast growth factor. Anastomosis bursting pressure, histopathological analysis, hydroxyproline content, and immunohistochemical results were better in the groups with rectal administration than in those with oral administration. CONCLUSION: These results had showed us that phenytoin administration resulted in enhanced stability of colonic anastomoses during the first postoperative week and rectal administration showed better results than oral administration.

Effect of nifedipine on the healing of left colonic anastomoses in rats.

PURPOSE: Ca(2+) channel blockers inhibit collagenase production and have a vasodilatatory effect. They also restrict the formation of ischemia-reperfusion induced free oxygen radicals. The aim of this study was to assess the effect of nifedipine on the healing of colonic anastomoses in a rat model. METHODS: Sixty Wistar rats weighing 240-290 g were divided into four groups of 15 rats each: a 3rd day control group (group A), a 3rd day treatment group (group B), a 7th day control group (group C), and a 7th day treatment group (group D). The treatment groups were given Nifedipine 3 mg/kg per day orally as three divided doses. RESULTS: The bursting pressure values of the anastomoses in the treatment groups were significantly higher than those in the control groups ( P < 0.05). The hydroxyproline content was also significantly higher in the treatment groups than in the control groups ( P < 0.05). Histologic examination confirmed that nifedipine treatment significantly increased collagen deposition and fibroblast ingrowth compared with controls ( P < 0.05). CONCLUSIONS: These results clearly showed that nifedipine enhanced the stability of colonic anastomoses during the first postoperative week.

Relaxant effect of omeprazole and lansoprazole in guinea pig gallbladder muscle strips in vitro.

BACKGROUND: The aim of this study was to investigate the role of omeprazole and lansoprazole, H(+)-K(+) ATPase inhibitors, in gallbladder smooth muscle contractility in vitro. METHODS: Gallbladder muscle strips obtained from guinea pigs were mounted in an organ bath. The responses of both precontracted strips and strips under basal tension to omeprazole and lansoprazole were determined. RESULTS: Spontaneous contractile activity was blocked following omeprazole and lansoprazole administration. The agents also caused concentration-dependent relaxation in carbachol- and KCl-precontracted gallbladder muscle strips. Pretreatment with atropine (1 microM), N(W)-nitro L-arginine methyl ester (L-NAME; 30 microM), indomethacin (10 microM), ammonium chloride (7.5 mM), sodium acetate (7.5 mM), tetraethylammonium chloride (0.5 mM), glibenclamide (1 micro M), 4-aminopyridine (0.1 mM), or clotrimazole did not inhibit this relaxation. Gallbladder strips were placed in high-concentrtion potassium (80 mM), calcium-free solution. The contraction produced with the addition of Ca(2+) (2.5 mM) was completely relaxed by omeprazole, lansoprazole, and nifedipine separately. CONCLUSIONS: These results demonstrate that omeprazole and lansoprazole have potent inhibitory effects on spontaneous contractions and cause dose-dependent relaxation in precontracted gallbladder smooth muscle strips of guinea pig in vitro. This effect could be due to blockade of the calcium channels.