Antioxidant Effect of Ukrain Versus N-Acetylcysteine Against Acute Biliary Pancreatitis in An Experimental Rat Model.

Purpose/Aim: Oxidative stress plays an important role in the pathogenesis of acute pancreatitis (AP). We compared the therapeutic effects of Ukrain (NSC 631570) and N-acetylcysteine (NAC) in rats with AP. MATERIALS AND METHODS: Forty male Sprague Dawley rats were divided into four groups: controls; AP; AP with NAC; and AP with Ukrain. AP was induced via the ligation of the bile-pancreatic duct; drugs were administered intraperitoneally (i.p.) 30 min and 12 h after AP induction. Twenty-four hours after AP induction, animals were sacrificed and the pancreas was excised. Levels of malondialdehyde (MDA) and nitric oxide (NO), and activity levels of tumor necrosis factor (TNF)-α, and myeloperoxidase (MPO) were measured in tissue samples. Total oxidant status (TOS), total antioxidant status (TAS), and total bilirubin, as well as activity levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), amylase and lipase were measured in serum samples. Pancreatic tissue histopathology was also evaluated. RESULTS: Test drugs reduced levels of MDA, NO, TNF-α, total bilirubin, AST, ALT, TOS and MPO, amylase and lipase activities (P < 0.001), and increased TAS (P < 0.001). Rats treated with test drugs attenuated AP-induced morphologic changes and decreased pancreatic damage scores compared with the AP group (P < 0.05). Both test drugs attenuated pancreatic damage, but the therapeutic effect was more pronounced in rats that received Ukrain than in those receiving NAC. CONCLUSIONS: These results suggest that treatment with Ukrain or NAC can reduce pancreatic damage via anti-inflammatory and antioxidant effects.

A novel combination treatment for breast cancer cells involving BAPTA-AM and proteasome inhibitor bortezomib.

Glucose-regulated protein 78 kDa/binding immunoglobulin protein (GRP78/BIP) is a well-known endoplasmic reticulum (ER) chaperone protein regulating ER stress by facilitating protein folding, assembly and Ca2+ binding. GRP78 is also a member of the heat shock protein 70 gene family and induces tumor cell survival and resistance to chemotherapeutics. Bortezomib is a highly specific 26S proteasome inhibitor that has been approved as treatment for patients with multiple myeloma. The present study first examined the dose- and time-dependent effects of bortezomib on GRP78 expression levels in the highly metastatic mouse breast cancer 4T1 cell line using western blot analysis. The analysis results revealed that GRP78 levels were significantly increased by bortezomib at a dose as low as 10 nM. Time-dependent experiments indicated that the accumulation of GRP78 was initiated after a 24 h incubation period following the addition of 10 nM bortezomib. Subsequently, the present study determined the half maximal inhibitory concentration of intracellular calcium chelator BAPTA-AM (13.6 µM) on 4T1 cells. The combination effect of BAPTA-AM and bortezomib on the 4T1 cells was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and WST-1 assays and an iCELLigence system. The results revealed that the combination of 10 nM bortezomib + 5 µM BAPTA-AM is more cytotoxic compared with monotherapies, including 10 nM bortezomib, 1 µM BAPTA-AM and 5 µM BAPTA-AM. In addition, the present results revealed that bortezomib + BAPTA-AM combination causes cell death through the induction of apoptosis. The present results also revealed that bortezomib + BAPTA-AM combination-induced apoptosis is associated with a clear increase in the phosphorylation of stress-activated protein kinase/Jun amino-terminal kinase SAPK/JNK. Overall, the present results suggest that bortezomib and BAPTA-AM combination therapy may be a novel therapeutic strategy for breast cancer treatment.

Effect of ukrain on ischemia/reperfusion-induced kidney injury in rats.

BACKGROUND: The aim of this study was to investigate the potential protective effect of ukrain on an experimental kidney injury model induced by ischemia and reperfusion (IR) in rats. MATERIAL AND METHODS: A total of 24 male Sprague-Dawley rats were equally and randomly separated into three groups as follows: group-1: controls (C; only laparotomy); group 2: renal ischemia-reperfusion (IR; occlusion of the renal artery for 30 min and 2 h of reperfusion); and group 3: ukrain treatment and IR applied group (U + IR; occlusion of the renal artery for 30 min and 2 h of reperfusion; ukrain was intraperitoneally administered 1 h before the IR process). RESULTS: Serum total oxidant status (TOS) and total antioxidant status (TAS) levels were measured. The oxidative stress index was determined by calculating the TOS/TAS ratio. TAS serum levels significantly increased, and TOS serum levels also prominently decreased in U + IR group, when compared with the IR group (P < 0.001). Mean NGAL level was remarkably higher in IR group, when compared with the U + IR group (P < 0.001). Caspase-3 messenger RNA (mRNA) expression level increased in IR and decreased in U + IR group (P < 0.001). Bcl-xL serum and mRNA expression levels increased in the U + IR group (P < 0.001). In addition, serum iNOS and mRNA expression levels increased in IR group and decreased in U + IR group (P < 0.001). CONCLUSIONS: Data established from the present study suggest that ukrain may exhibit protective effect against IR-induced kidney injury and that antioxidant activity primarily modulates this effect.

Ukrain (NSC 631570) ameliorates intestinal ischemia-reperfusion-induced acute lung injury by reducing oxidative stress.

Intestinal ischemia-reperfusion (I/R) causes severe destruction in remote organs. Lung damage is a frequently seen complication after intestinal I/R. Ukrain (NSC 631570) is a synthetic thiophosphate derivative of alkaloids from the extract of the celandine (Chelidonium majus L.) plant. We investigated the effect of Ukrain in animals with lung injury induced by intestinal I/R. Adult male Spraque-Dawley rats were randomly divided into four groups: control, Ukrain, I/R, I/R with Ukrain. Before intestinal I/R was induced, Ukrain was administered intraperitoneally at a dose of 7.0 mg/body weight. After 1 h ischemia and 2 h reperfusion period, lung tissues were excised. Tissue levels of total oxidative status (TOS), total antioxidant status (TAS) were measured and oxidative stress indices (OSI) were calculated. Lung tissues were also examined histopathologically. TOS and OSI levels markedly increased and TAS levels decreased in the I/R group compared to the control group (P < 0.05). TOS and OSI levels markedly decreased and TAS levels increased in the I/R with Ukrain group compared with the group subjected to IR only (P < 0.05). Severe hemorrhage, alveolar septal thickening, and leukocyte infiltration were observed  in the I/R group. In the I/R with Ukrain group, morphologic changes occurring as a result of lung damage attenuated and histopathological scores reduced compared to the I/R group (P < 0.05). Our results suggest that Ukrain pretreatment could reduce lung injury induced by intestinal I/R induced via anti-inflammatory and antioxidant effects.

Is there a correlation between maternal serum TGF-ß1 levels and fetal hydronephrosis?

OBJECTIVE: We aimed to identify a noninvasive marker for clinically significant fetal uropathies. To achieve this aim, we detected TGF (transforming growth factor)-ß1 serum level which rises in neonatal hydronephrosis, in pregnant patients with fetal hydronephrosis. MATERIALS AND METHODS: We evaluated 44 patients, all of whom were pregnant and had a gestational age between 20 and 30 weeks. Twenty-two patients had normal maternal renal ultrasound imaging and had a fetus with fetal hydronephrosis (Group A). The remaining twenty-two patients had normal maternal and fetal renal ultrasound imaging (Group B). The maternal serum levels of TGF-ß1 were measured with a sandwich enzyme-linked immunosorbent assay (ELISA) using a commercially available kit. RESULTS: The median value for the study group was 55.90 pg/mL (9.67 ± 574.45) and for the control group was 59.49 pg/mL (12.49 ± 402.04). There was no statistical difference in serum TGF-ß1 levels between the groups (p = 0.769 - Mann-Whitney U test). In the study group, the diameter of the right renal pelvis was 5.7 mm (5.1-8.9 mm), while the diameter of left renal pelvis was 5.75 mm (5.3-10.04 mm). CONCLUSION: In our study, the circulating TGF-ß1 levels were not statistically different in the fetal hydronephrosis group when compared to the controls. According to our study, TGF-ß1 is not useful in the detection and follow-up of fetal hydronephrosis. We therefore require further studies involving larger groups with moderate or severe fetal hydronephrosis to detect the usefulness of the serum levels of TGF-ß1 in pregnant women with fetal hydronephrosis.

Endoscopic Removal of 15 Gastrointestinal Foreign Bodies.

Foreign body ingestion occurs commonly in children, elderly, mentally impaired or alcoholic, and psychiatric patients. We present a 15-year-old boy with mental retardation and uncontrolled psychiatric disorder admitted to the hospital with abdominal and chest pain. He was diagnosed with foreign body ingestion and 15 foreign objects, including a sharp knife, were successfully removed endoscopically by using an over-tube.

Enteric duplication cyst located at the posterior tongue: a rare case report and review of the literature.

The lingual localization of an enteric duplication is extremely rare but may present with respiratory and feeding problems that require emergency intervention. A 7-month-old boy was brought to our clinic with feeding difficulties and tongue swelling. Physical examination showed a cystic lesion located near the left side of the tongue base that caused tongue protrusion to the contralateral side. During surgery, a 3-cm diameter opaque thick-walled cyst was found to be very closely adherent to the base of tongue, which was excised in its entirety. Following surgery, the patient fed during the early postoperative period and no complications were observed other than hypersalivation. On histological examination, a cystic lesion lined with intestinal mucosa and goblet cells was found. We present the rare case of a duplication cyst of the posterior tongue, with a literature review.

Effects of ukrain in rats with intestinal ischemia and reperfusion.

BACKGROUND: The purpose of this study is to investigate the potential protective effect of the ukrain on ischemia-reperfusion (IR) injury in rat intestine, which has not previously been studied. METHODS: Thirty-one male Sprague-Dawley rats were randomly assigned to four groups, each consisting of eight rats as follows: (1) a sham group (S) (laparotomy, but no IR injury); (2) ukrain group (U) (no IR, and ukrain was administered intraperitoneally 1 h before laparotomy); (3) intestinal ischemia-reperfusion (II/R) group (30-min occlusion of the superior mesenteric artery then 2-h reperfusion); and (4) ukrain + II/R group (U + II/R) (30-min occlusion of the superior mesenteric artery then 2-h reperfusion; ukrain was administered intraperitoneally 1 h before IR). RESULTS: Serum total oxidant status (TOS) and total antioxidant status (TAS) were measured using Erel method. Oxidative stress index was calculated using the TOS/TAS ratio. TAS levels increased and TOS serum levels were also significantly decreased in the ukrain + IR group compared with the IR group (P = 0.000 and P = 0.015). CONCLUSIONS: In this study, we demonstrated for the first time in literature that ukrain helps to prevent intestinal tissue breakdown against II/R injury and that this effect can be achieved by antioxidant activities.

Effects of Ukrain on intestinal apoptosis caused by ischemia-reperfusion injury in rats.

BACKGROUND: To investigate the antiapoptotic effect of Ukrain on intestinal lesion induced by mesenteric ischemia-reperfusion (I/R) injury. METHODS: Male Sprague-Dawley rats were divided into three groups: laparotomy (L), I/R, and Ukrain and I/R (U + I/R). In the U + I/R group, Ukrain (7 mg/kg) was given by intraperitoneal at the beginning of the study. 1 h after ukrain application, ischemia was induced for 30 minutes, and reperfusion was subsequently allowed for 120 minutes in the I/R and U + I/R groups. Rats were sacrificed at the end of reperfusion and intestinal tissues were collected for biochemical and molecular examination. Intestinal tissues caspase 3 protein were assayed. Serum Bcl-xL and iNOS were measured. The expression level of caspase-3, Bcl-xL and iNOS in intestinal tissue of rats were detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Levels of serum iNOS and mRNA expression were increased in the I/R and decreased in the U + I/R group. In addition, levels of the proapoptotic gene caspase-3 protein and mRNA expression were increased in the I/R and decreased in the U + I/R group. Levels of the antiapoptotic gene Bcl-xL serum and mRNA expression were increased in the U + I/R group. CONCLUSIONS: Ukrain can reduce the ischemia-reperfusion injury in the intestinal tissue by inhibiting the cell apoptosis. The mechanism may be correlated with increased Bcl-xL mRNA expressions and decreased mRNA expressions of Caspase-3 and iNOS.

Mean platelet volume levels in children with adenoid hypertrophy.

Adenoid hypertrophy (AH) is a common disorder in children, resulting in chronic nasal congestion. This chronic congestion should be evaluated carefully because it can lead to chronic upper airway obstruction. Many authors have suggested that increased nasal resistance to respiration may cause disturbances in the pulmonary ventilation and carry the risk of cardiopulmonary diseases. Mean platelet volume (MPV) is a marker of platelet function and is positively associated with indicators of platelet activity. Mean platelet volume is an indicator of larger and more reactive platelets and has been shown to be increased in patients with vascular disease, including peripheral, pulmonary, and coronary artery disease. Recently, MPV levels have also been shown to be increased in patients with severe obstructive sleep apnea, and marked nasal septal deviation. Moreover, increased MPV has also been shown to have a prognostic role in cardiovascular disease. We investigated whether MPV is higher in patients with AH and whether higher MPV levels can be reduced by adenoidectomy. To the best of our knowledge, this is the first study to investigate MPV in patients with AH. Our results suggest that MPV, a determinant of platelet activation, is elevated in patients with AH and adenoidectomy is an effective therapeutic measure in such patients. Increased platelet activation may be related to an increase of cardiopulmonary risk in patients with AH.

Anticancer agent ukrain and bortezomib combination is synergistic in 4T1 breast cancer cells.

The identification and in-depth understanding of intracellular signalling pathways led to the synthesis and discovery of many agents targeting cancer cells. In this study, we investigated for the first time the effect of anticancer agent ukrain as a single agent or in combination with cisplatin, etoposide, 5-fluorouracil, quercetin and bortezomib in 4T1 breast cancer and B16F10 melanoma cells. It was found that ukrain is cytotoxic and apoptotic in 4T1 breast carcinoma and B16F10 melanoma cells when given alone. The IC50 value of ukrain in 4T1 cells was found as 40 ± 6.8 µM and that in B16F10 cells as 76 ± 10 µM. It was then found that apoptosis can be induced in 4T1 breast cancer cells in a dose-dependent manner in response to ukrain treatment, based on DNA fragmentation evidence. The induction of apoptosis was corroborated by the analysis of cleavage products of caspase-3 in 4T1 cells using Western blot technique. When ukrain was tested in combination with cisplatin and etoposide, no significant enhancement of cytotoxicity was detected as compared with single agent treatments. Similarly, 5-fluorouracil and quercetin also did not potentiate the cytotoxic effects of ukrain in 4T1 cells. Finally, we examined the effect of various concentrations of ukrain in combination with 10 nM bortezomib in 4T1 cells. Determination of combination index values showed that bortezomib potentiated the effect of ukrain. And the combination was found to cause synergistic cell death. The lowest combination index detected was 0.57 which was obtained when the cells were treated with 10 nM bortezomib + 100 µM ukrain. Likewise, when cells were treated with different doses of bortezomib in the presence of 25 µM ukrain, synergism was similarly detected between the two drugs in a dose-dependent manner. Altogether, the results presented here suggest that the combination of ukrain + bortezomib may be further evaluated and tested in clinical settings.

Knowledge, attitude and behaviour of boys and parents about circumcision.

AIM: To determine the knowledge, attitude and behaviour of parents and previously circumcised early adolescent boys about circumcision. METHODS: Half of the boys attending the sixth class of the primary school in our city centre and their parents were included in this cross-sectional, descriptive study. Questionnaires were prepared by the authors, which include 38 questions for parents and 25 questions for boys. RESULTS: Sixty-six per cent of the students were circumcised at the age of 7 years and above, 26% between three and 6 years and 8% below 3 years of age. Forty-two per cent of boys were circumcised by a traditional circumciser and 64% were circumcised at home. Main reasons of circumcision for parents were religious purposes (79%) and health issues (51%). When the boys were asked about their thoughts during circumcision, they mostly stated that 'it was necessary to become a man' (58%) and 'it would hurt much' (50%). Thirty-eight per cent of boys were frightened during circumcision and 46% were worried. Boys circumcised in the 7 years and above age group were most content about their age of circumcision. CONCLUSIONS: We consider that it is reasonable to wait up to an age at which the child could understand and participate in the decision of the concept and timing of circumcision.

A rare presentation of crush injury: transanal small bowel evisceration. Case report and review of the literature.

Evisceration of the small intestine through the anus is an extremely rare event in children. We report a 2-year-old boy who sustained transanal small bowel evisceration associated with bilateral diaphragmatic rupture, left diaphragmatic herniation, and spinal cord injury without radiographic abnormality which happened after crushing by motor vehicle. We reviewed children with transanal small bowel evisceration and discussed etiological differences between children and adult. We also discussed the basic principles of management and follow up in these patients.