Roles of adiponectin and leptin as diagnostic markers in pancreatic cancer.

NTRODUCTION: Obesity is one of the most serious public health problem worldwide. Adipose tissue synthetize and secrete many growth factors and several cytokines known as adipokines. Studies demonstrated changes in the levels of these adipokines in many types of cancer associated with obesity. In this study, we aimed to evaluate the possible relationship between adiponectin and leptin levels with pancreas cancer and disease stage, representative of Turkish population. MATERIALS AND METHODS: The study was conducted between April 2012 - November 2013. Study included 46 patients - 46 control subjects, who had pancreatic carcinoma. Results between the patients and the control group and relationship between the disease stage and results were evaluated. RESULTS: The comparison of preoperative adiponectin and leptin levels of the study group with the levels of the control group showed that there was no correlation with adiponectin and pancreas cancer. In contrast, leptin levels in the study group were significantly lower than in the control group. There was no correlation between the disease stage and adiponectin and leptin levels. CONCLUSION: There was a significant correlation between low leptin levels and pancreatic cancer, while adiponectin had no correlation. Differential diagnosis of pancreas cancer can be made by evaluating low leptin levels with elevated tumor markers (Tab. 3, Ref. 17).

Risk factors for mesh erosion after vaginal sling procedures for urinary incontinence.

OBJECTIVES: To identify risk factors for mesh erosion in women undergoing vaginal sling procedures for urinary incontinence with synthetic meshes, and to estimate the incidence of mesh erosion after these procedures. STUDY DESIGN: Retrospective study of women who underwent vaginal sling procedures between January 2007 and January 2013. In total, 1439 consecutive women with stress urinary incontinence were investigated. Five hundred and sixty-six (39.3%) women underwent a tension-free vaginal tape (TVT) procedure and 873 (60.7%) women underwent a transobturator tape (TOT) procedure. All procedures were performed using meshes of the same type and size. Women who experienced mesh erosion were defined as cases, and women who were not re-admitted or identified with mesh erosion during the study period were defined as controls. Demographics, operative techniques and outcomes were taken from medical records. Multivariate regression identified the odds of mesh erosion. RESULTS: Sixty-one of 1439 (4.2%) women were found to have mesh erosion in the postoperative period: 41 (67.2%) after TOT procedures and 20 (32.8%) after TVT procedures. The rate of mesh erosion was 4.7% in the TOT group and 3.5% in the TVT group, and this difference was significant (p<0.05). Mean age, body mass index, current smoking, menopausal status and diabetes mellitus were significantly higher among cases than controls. Univariate analysis showed that length of vaginal incision >2 cm, recurrent vaginal incision for postoperative complications, and previous pelvic organ prolapse or incontinence surgery were significant risk factors for erosion. Multivariate analysis demonstrated that older age, diabetes mellitus, current smoking, length of vaginal incision >2 cm, recurrent vaginal incision for postoperative complications, and previous pelvic organ prolapse or incontinence surgery were independent risk factors for mesh erosion. CONCLUSIONS: Mesh erosion following vaginal sling procedures is a frustrating complication with relatively low incidence. It was found to occur more often after TOT procedures than TVT procedures. Older age, diabetes mellitus, smoking, length of vaginal incision >2 cm, recurrent vaginal incision for postoperative complications, and previous vaginal surgery for pelvic organ prolapse or incontinence increased the risk of mesh erosion. Identification of risk factors may enable surgeons to prevent or minimize this complication.

Sildenafil accelerates liver regeneration after partial hepatectomy in rats.

OBJECTIVE: The regeneration process causes the liver to achieve an adequate volume and function after major hepatectomy or living donor liver transplantation. Sildenafil, a selective phosphodiesterase-5 inhibitor used for erectile dysfunction, impacts the liver by enhancing the effects of nitric oxide. The aim of this study was to investigate the influence of sildenafil on liver regeneration in rats after partial hepatectomy. METHODS: Sixty young female Wistar Albino rats were randomly divided into three equal groups before 70% hepatectomy. Thereafter, we administered intraperitoneal saline to the control group (G1); 10 µg/kg sildenafil to the low-dose group (G2) and 100 µg/kg to the high-dose sildenafil group (G3). Half of the rats per group were sacrificed on the first and the other half on the fifth postoperative day after partial hepatectomy. Regeneration was assessed using three methods: (1) the formula described by Kwon et al formula, (2) the average number of mitotic figures in 10 microscopic fields, and (3) the average of Ki-67-positive nuclei in 1000 cells using immunohistochemistry. RESULTS: Although, the hepatic regeneration and mitosis rates were similar in all three groups, Ki-67 levels were significantly higher in both G2 and G3 than the control group on the first postoperative day. Hepatic regeneration was significantly greater in G2 and G3 than the control group as was the mitosis rate in the G2 group versus the two groups. By the 5th postoperative day Ki-67 levels were similar in the three groups. CONCLUSION: Sildenafil treatment accelerated hepatic regeneration after partial hepatectomy in rats.

Use of granulocyte colony-stimulating factor for neutropenia after orthotopic liver transplantation: report of two cases.

Early postoperative infections are one of the major causes of morbidity and mortality following orthotopic liver transplantation. The severity of these infections may be increased in patients with neutropenia. There are no guidelines on the use of granulocyte colony-stimulating factor (G-CSF) for the treatment of neutropenia in posttransplant liver recipients. However, it has been recommended by several authors. We have herein presented two patients who were treated effectively with G-CSF. Both patients developed severe neutropenia (<500/mm(3)) on the third postoperative day, and received intravenous G-CSF administration for 3 days. The neutrophil counts gradually increased and additional infusions were not needed. The immunosuppressive and prophylactic treatments were not altered. G-CSF administration was used effectively for 3 days in our two patients. No evidence of infectious or acute rejection episode was encountered during or following G-CSF treatment.

Hybrid processing and anisotropic sintering shrinkage in textured ZnO ceramics.

We have studied the combined effects of the templated grain growth and magnetic alignment processes on sintering, anisotropic sintering shrinkage, microstructure development and texture in ZnO ceramics. Suspensions of 0-10 vol % ZnO template particles were slip cast in a 12 T rotating magnetic field. Sintering and texture characteristics were investigated via thermomechanical analysis and electron backscatter diffraction, respectively. Sintering as well as texture characteristics depend on template concentration. For the studied ZnO system, there is a critical template concentration (2 vol % in this study) above which densification is limited by the templates owing to constrained sintering. Below this limit, the densification is enhanced and the anisotropic shrinkage is reduced, which is attributed to densifying characteristics of the templates.

The incidence and management of acute and chronic rejection after living donor liver transplantation.

Living donor liver transplantation (LDLT) is a good alternative to cadaveric liver transplantation for end-stage liver disease. Herein we report the outcome of 132 LDLTs performed between 1999 and 2005, with special emphasis on the incidence and management of acute and chronic rejection. Among the LDLT population a first acute rejection episode (ARE) was clinically suspected in 24% and proven by liver biopsy in 11%. According to the Banff classification, 50% of AREs were grade 1, and 50%, grade 2. There was no grade 3 AREs. The first ARE occurred between 7 days and 23 months posttransplantation (mean 97 days, median 70 days). Ninety-seven percent (31/32) of the AREs occurred within the first year after transplantation and 3% (1/32) in the second year. Among the patients with ARE, 23% developed a second ARE between 4 and 11 months. A third ARE was detected in 8% of patients after month 18. All AREs responded to adjustment of immunosuppressive doses or steroid boluses. Chronic rejection (CR) was detected in 2%. In conclusion, the incidences of ARE and CR are consistent with the previously reported data. Acute and chronic rejections seem to be mild and easily manageable clinical conditions. Our results also showed a significant difference between clinically suspected and biopsy-proven ARE emphasizing the importance of indicated liver biopsies in the management of the LDLT population.

Risk factors for excess weight loss and hypernatremia in exclusively breast-fed infants.

Data were prospectively obtained from exclusively breast-fed healthy term neonates at birth and from healthy mothers with no obstetric complication to determine risk factors for excess weight loss and hypernatremia in exclusively breast-fed infants. Thirty-four neonates with a weight loss > or = 10% were diagnosed between April 2001 and January 2005. Six of 18 infants who were eligible for the study had hypernatremia. Breast conditions associated with breast-feeding difficulties (P < 0.05), primiparity (P < 0.005), less than four stools (P < 0.001), pink diaper (P < 0.001), delay at initiation of first breast giving (P < 0.01), birth by cesarean section (P < 0.05), extra heater usage (P < 0.005), extra heater usage among mothers who had appropriate conditions associated with breast-feeding (P < 0.001), mean weight loss in neonates with pink diaper (P < 0.05), mean uric acid concentration in neonates with pink diaper (P < 0.0001), fever in hypernatremic neonates (P < 0.02), and the correlation of weight loss with both serum sodium and uric acid concentrations (P < 0.02) were determined. Excessive weight loss occurs in exclusively breast-fed infants and can be complicated by hypernatremia and other morbidities. Prompt initiation of breast-feeding after delivery and prompt intervention if problems occur with breast-feeding, in particular poor breast attachment, breast engorgement, delayed breast milk "coming in", and nipple problems will help promote successful breast-feeding. Careful follow-up of breast-feeding dyads after discharge from hospital, especially regarding infant weight, is important to help detect inadequate breast-feeding. Environmental factors such as heaters may exacerbate infant dehydration.

Risk factors for excess weight loss and hypernatremia in exclusively breast-fed infants

Data were prospectively obtained from exclusively breast-fed healthy term neonates at birth and from healthy mothers with no obstetric complication to determine risk factors for excess weight loss and hypernatremia in exclusively breast-fed infants. Thirty-four neonates with a weight loss > or = 10 percent were diagnosed between April 2001 and January 2005. Six of 18 infants who were eligible for the study had hypernatremia. Breast conditions associated with breast-feeding difficulties (P < 0.05), primiparity (P < 0.005), less than four stools (P < 0.001), pink diaper (P < 0.001), delay at initiation of first breast giving (P < 0.01), birth by cesarean section (P < 0.05), extra heater usage (P < 0.005), extra heater usage among mothers who had appropriate conditions associated with breast-feeding (P < 0.001), mean weight loss in neonates with pink diaper (P < 0.05), mean uric acid concentration in neonates with pink diaper (P < 0.0001), fever in hypernatremic neonates (P < 0.02), and the correlation of weight loss with both serum sodium and uric acid concentrations (P < 0.02) were determined. Excessive weight loss occurs in exclusively breast-fed infants and can be complicated by hypernatremia and other morbidities. Prompt initiation of breast-feeding after delivery and prompt intervention if problems occur with breast-feeding, in particular poor breast attachment, breast engorgement, delayed breast milk "coming in", and nipple problems will help promote successful breast-feeding. Careful follow-up of breast-feeding dyads after discharge from hospital, especially regarding infant weight, is important to help detect inadequate breast-feeding. Environmental factors such as heaters may exacerbate infant dehydration.

Atrial fibrillation after electrical shock: a case report and review.

A 52 year old man was admitted to an emergency department with a fast ventricular rate atrial fibrillation after an electrical shock. Electrical cardioversion was attempted after echocardiographic examination. This failed, but the heart rate slowed. Successful pharmacological cardioversion was achieved after 16 hours of amiodarone infusion. Pre-excitation syndrome was detected on baseline echocardiograph. Serum cardiac specific markers were all within normal limits. No abnormal findings were detected by chest radiography, echocardiographic, or coronary angiographic investigations. Acute onset atrial fibrillation after electrical injury is discussed.

[Effect of antithrombin-III (AT-III) on intestinal epithelium changes related to obstructive icterus: experimental study in rats]. / Etude de l'effet de l'antithrombine-III (AT-III) sur les modifications de l'épithélium intestinal liées à l'ictère obstructif: étude expérimentale chez le rat.

PURPOSE: Bacterial translocation leading to sepsis is increased by obstructive jaundice(OJ). Antithrombin III (ATIII) mediates the promotion of prostaglandin release, an inhibitor of leucocyte activation and downregulator of many proinflammatory cytokines. We investigated the effect of ATIII on histopatology and villus morphology of small intestine. MATERIAL AND METHODS: We designed an experimental study with 40 rats who were divided into four groups. The first one (control, n = 10) received saline, the second (n = 10) included normal rats who received ATIII, the third group (n = 10) was rats with OJ (ligation of common bile duct), and the fourth group included OJ rats receiving AT-III. AT-III (100 UI/kg intraperitoneally) was started at the third day following bile duct ligation and repeated for 5 days. At the 8 day, rats were scarified and ileum was analysed. Histopathological assessments were performed, using a grading scheme ranging from 0 to 10 (Chui et al). RESULTS: Median histological score was found to be 2 in group 1, 1.71 in group 2, 5.43 in group 3 and 2.71 in group 4. The difference between group 3 and 4 was statistically significant. Mucosal thicknesses and villus lengths were found significantly lower in OJ group. Mucosal thicknesses and villus lengths were significantly preserved in jaundiced + AT-III group. CONCLUSION: ATIII demonstrated a salutary effect on the histopathological changes caused by the OJ and prevented the adverse effects on histopathological and morphological parameters in ileal mucosa.

Method dependence of apparent stoichiometry in the binding of salicylate ion to human serum albumin: a comparison between equilibrium dialysis and fluorescence titration.

The binding of salicylate ion to human serum albumin (HSA) was studied in 100 mM potassium phosphate buffer (pH 7.4, 25 degrees C), using equilibrium dialysis and fluorescence titration methods. The protein samples tested were (a) dialyzed human plasma and (b) a commercial preparation of HSA, essentially free of globulin and fatty acids. Independent of the analytical method used, Scatchard and nonlinear regression analyses of the data pointed to a single class of high-affinity salicylate binding sites. On the other hand, the binding parameters were found to be method dependent. K(d) ranged between 25 +/- 2.4 and 62 +/- 15 microM in equilibrium dialysis and between 10 +/- 1.3 and 40 +/- 3.0 microM in fluorescence titration. (The higher limits refer to plasma samples at high [HSA]). Following the same pattern, the apparent stoichiometry of binding (though independent of sample identity and concentration) was higher in equilibrium dialysis (n(app) = 3.2 +/- 0.10) than in fluorescence titration (n(app) 1.9 +/- 0.30). The difference between the two methods could be reconciled by invoking two distinct classes of binding sites (I and II), which had identical (or marginally different) K(d) values, while differing in the magnitude of the fluorescence signal (Deltaf) generated upon ligand binding (Deltaf, PL(I) = Deltaf(I); Deltaf, PL(II) = 0). Further, it was assumed that the state of occupation of class II sites affected the fluorescence efficiency of class I sites, such that Deltaf, PL(I,II) = betaDeltaf(I) (beta = interaction factor). A random binding scheme involving P, PL(I), PL(II), and PL(I,II) was formulated. The model adequately predicted the behavior of the system when monitored through the change in protein fluorescence: Taking K(d) = 25 microM and n(T) = 3, the interaction factor beta was found to be 0.62 +/- 0.10. It was concluded that the correct parameters for the binding of salicylate ion to HSA are K(d) = 25 +/- 2.4 microM and n(T) = 3.2 +/- 0.10, as indicated by equilibrium dialysis of purified HSA. Besides updating information relating to the salicylate binding potential of HSA, this study serves to illustrate a likely complication in the study of protein-ligand interactions by fluorometric methods.

Fluorescence monitoring of the conformational change in alpha 2-macroglobulin induced by trypsin under second-order conditions: the macroglobulin acts both as a substrate and a competitive inhibitor of the protease.

The reaction of bovine pancreatic trypsin with human plasma alpha(2)-macroglobulin (alpha(2)M) was studied at 25 degrees C, using equimolar mixtures of E and I in 50 mM potassium phosphate buffer, pH 7. The conformational change in alpha(2)M was monitored through the increase in protein fluorescence at 320 nm (exc lambda, 280 nm). At [alpha(2)M](0) =[E](0) =11.5-200 nM, the fluorescence change data fit the integrated second-order rate equation, (F(infinity) -F(0) )/(F(infinity) -F(t) )=1+k(i,obsd) [alpha(2)M](0) t, indicating that cleavage of the bait region in alpha(2)M was the rate-determining step. The apparent rate constant (k(i,obsd)) was found to be inversely related to reactant concentration. The kinetic behavior of the system was compatible with a model involving reversible, nonbait region binding of E to alpha(2)M, competitively limiting the concentration of E available for bait region cleavage. The intrinsic value of k(i) was (1.7+/-0.24) x 10(7) M(-1) s(-1).K(p), the inhibitory constant associated with peripheral binding, was estimated to be in the submicromolar range. The results of the present study point to a potential problem in interpreting kinetic data relating to protease-induced structural changes in macromolecular substrates. If there is nonproductive binding, as in the case of trypsin and alpha(2)M, and the reactions are monitored under pseudo first-order conditions ([S](0) >>[E](0) ), an intrinsically second-order process (such as the rate-limiting bait region cleavage in alpha(2)M) may become kinetically indistinguishable from an intrinsically first-order process (e.g. rate-limiting conformational change). Hence an excess of one component over the other should be avoided in kinetic studies addressing such systems.

The trypsin-inhibitory efficiency of human alpha 2-macroglobulin in the presence of alpha 1-proteinase inhibitor: evidence for the formation of an alpha 2-macroglobulin--alpha 1-proteinase inhibitor complex.

The inhibition of bovine pancreatic trypsin was studied at pH 7, 25 degrees C, using mixtures of purified human alpha 2-macroglobulin (alpha 2M) and alpha 1-proteinase inhibitor (alpha 1 PI). The partitioning of the enzyme between the two inhibitors was determined by comparing control esterase activity, assayed with N-benzoyl-L-arginine ethyl ester as substrate, with that remaining after incubation with inhibitory mixtures. (At [I]0 > [E]0, remaining esteratic activity reflects the concentration of alpha 2M-associated enzyme (alpha 2M-E*) and the concentration of alpha 1PI-associated, inactive enzyme (alpha 1PI-E*) is given by the difference, [E]0-[alpha 2M-E*].) The pattern of product distribution was found to be incompatible with an inhibitory model involving parallel, second-order reactions of E with alpha 2M and alpha 1PI. The data pointed to complex formation between the two inhibitors, limiting the level of alpha 2M readily available for reaction with E. Analysis based on the binding equilibrium, alpha 2M (dimeric unit) + alpha 1PI reversible alpha 2M-alpha 1PI, yielded Kd = 2.1 +/- 0.3 microM. Complex formation between alpha 2M and alpha 1PI was verified by gel permeation experiments. alpha 2M was found to restrict the volume of distribution of alpha 1PI in Sephadex G200 beds. Kd, deduced from gel permeation behaviour, was 0.8 +/- 0.32 microM. Preliminary kinetic experiments with dialyzed plasma suggested that the alpha 2M-alpha 1PI interaction is effective also in vivo. Given Kd and the mean plasma levels of the two inhibitors ([alpha 2M] = 2 microM; [alpha 1PI] = 36 microM), it was estimated that > 90% of alpha 2M in human circulation must be complexed to alpha 1PI and lack immediate antiproteinase activity.

Kinetic analysis of enzyme inactivation under second-order conditions by use of substrate-to-product progress curves: application to the inhibition of trypsin by alpha-1 proteinase inhibitor.

The inhibition of bovine pancreatic trypsin by human alpha-1 proteinase inhibitor (alpha-1 PI) was studied under second-order conditions by continuously monitoring the fluorescence change due to the enzymatic hydrolysis of N alpha-benzoyl-L-arginine 7-amido-4-methyl-coumarin as substrate. Employing equimolar starting concentrations of enzyme and inhibitor (110-220 nM), the fluorescence progress curve was analyzed according to the equation Pt = (kcat[S]/kiKm)In[ki[E]0t + 1], where ki is the second-order rate constant for the reaction, E + alpha-1 PI-->E* alpha-1 PI (inactive). ki was found to be 1.8 +/- 0.16 x 10(7) M-1 min-1 (at pH 7.0 and 25 degrees C), in close agreement with results obtained by alternative kinetic methods. The method reported appears to be valid and should be useful in the study of fast reactions where one of the reaction partners is an enzyme. An extension of the second-order progress curve approach to cover unequimolar mixtures of E and I is also offered.

A study on the route of 1-methylurate formation in theophylline metabolism.

The urinary excretion patterns of theophylline metabolites were studied in a subject on a routine, oral dose of 600 mg/day. The highest correlation was observed between the excretions of 1,3-dimethylurate and 1-methylurate (r = 0.73 +/- 0.08). The poorest correlations were observed when the excretion of 1-methylxanthine was compared to those of 1-methylurate and 1,3-dimethylurate (r < or = 0.55, P > or = 0.05). The difference in the quality of the correlations was not due to rate-limiting or class-specific carries. The results suggested that 1-methylurate did not derive solely from 1-methylxanthine, implicating 1,3-dimethylurate as an alternative source. When the theophylline regimen was supplemented by a single dose of caffeine (4.80 mg/kg), the recovery of unaltered caffeine and the yield of metabolites arising from the primary 3-demethylation of caffeine (1-methylxanthine, 7-methylxanthine, 1-methylurate, 1,7-dimethylxanthine and 1,7-dimethylurate) were found to be unchanged. The lack of competition between caffeine and theophylline indicated that caffeine 3-demethylation and the demethylations of theophylline are not catalyzed by the same cytochrome P450 system.

5-methyl-8-N-substituted-thiocarbamoyl-7,8-diazabicyclo[4.3.0] non-6-enes: evaluation as BSAO inhibitors and pharmacological activity screening.

In this study a series of 5-methyl-8-N-substituted-thiocarbamoyl-7,8-diazabicyclo[4.3.0] non-6-enes derivatives previously synthesized and separated to their stereoisomers, were evaluated as BSAO inhibitors and screened pharmacologically for antidepressant activity, effect on anxiety and experimental parkinsonism by in vivo tests. The title compounds caused 30-40% inhibition irrespective of geometric isomerism as well as nature of substituent. On the other hand, their open chain derivative NBE (4-ethyl, p-methoxybenzylidenthiosemicarbazide) showed a marked enzyme inhibition and antidepressant effect. While the other group was inactive as antidepressant effect, these compounds have shown diastereoselective antitremor activity by inhibiting the tremors induced by oxotremorin in mice pretreated with dopaminergic antagonist haloperidol. The title compounds constitutes a new class of BSAO inhibitors and may serve as usefull leads for further investigation as specific BSAO inhibitors, antiparkinson, antidepressant and anticholinergic agents.