Mechanistic insights into the inhibition of human placental glutathione S-transferase P1-1 by abscisic and gibberellic acids: An integrated experimental and computational study.

The interactions of the classic phytohormones gibberellic acid (gibberellin A3 , GA3 ) and abscisic acid (dormin, ABA), which antagonistically regulate several developmental processes and stress responses in higher plants, with human placental glutathione S-transferase P1-1 (hpGSTP1-1), an enzyme that plays a role in endo- or xenobiotic detoxification and regulation of cell survival and apoptosis, were investigated. The inhibitory potencies of ABA and GA3 against hpGSTP1, as well as the types of inhibition and the kinetic parameters, were determined by making use of both enzyme kinetic graphs and SPSS nonlinear regression models. The structural basis for the interaction between hpGSTP1-1 and phytohormones was predicted with the aid of molecular docking simulations. The IC50 values of ABA and GA3 were 5.3 and 5.0 mM, respectively. Both phytohormones inhibited hpGSTP1-1 in competitive manner with respect to the cosubstrates GSH and CDNB. When ABA was the inhibitor at [CDNB]f -[GSH]v and at [GSH]f -[CDNB]v , Vm , Km , and Ki values were statistically estimated to be 205 ± 16 µmol/min-mg protein, 1.32 ± 0.18 mM, 1.95 ± 0.25 mM and 175 ± 6 µmol/min-mg protein, 0.85 ± 0.06 mM, 1.85 ± 0.16 mM, respectively. On the other hand, the kinetic parameters Vm , Km , and Ki obtained with GA3 at [CDNB]f -[GSH]v and at [GSH]f -[CDNB]v were found to be 303 ± 14 µmol/min-mg protein, 1.77 ± 0.13 mM, 3.38 ± 0.26 mM and 249 ± 7 µmol/min-mg protein, 1.43 ± 0.07 mM, 2.89 ± 0.19 mM, respectively. Both phytohormones had the potential to engage in hydrogen-bonding and electrostatic interactions with the key residues that line the G- and H-sites of the enzyme's catalytic center. Inhibitory actions of ABA/GA3 on hpGSTP1-1 may guide medicinal chemists through the structure-based design of novel antineoplastic agents. It should be noted, however, that the same interactions may also render fetuses vulnerable to the potentially toxic effects of xenobiotics and noxious endobiotics.

Conversations in the Gut: The Role of Quorum Sensing in Normobiosis.

An imbalance in gut microbiota, termed dysbiosis, has been shown to affect host health. Several factors, including dietary changes, have been reported to cause dysbiosis with its associated pathologies that include inflammatory bowel disease, cancer, obesity, depression, and autism. We recently demonstrated the inhibitory effects of artificial sweeteners on bacterial quorum sensing (QS) and proposed that QS inhibition may be one mechanism behind such dysbiosis. QS is a complex network of cell-cell communication that is mediated by small diffusible molecules known as autoinducers (AIs). Using AIs, bacteria interact with one another and coordinate their gene expression based on their population density for the benefit of the whole community or one group over another. Bacteria that cannot synthesize their own AIs secretly "listen" to the signals produced by other bacteria, a phenomenon known as "eavesdropping". AIs impact gut microbiota equilibrium by mediating intra- and interspecies interactions as well as interkingdom communication. In this review, we discuss the role of QS in normobiosis (the normal balance of bacteria in the gut) and how interference in QS causes gut microbial imbalance. First, we present a review of QS discovery and then highlight the various QS signaling molecules used by bacteria in the gut. We also explore strategies that promote gut bacterial activity via QS activation and provide prospects for the future.

Gastric cancer diagnosis and staging in coronavirus disease 2019 (Covid-19) pandemic.

AIM: The aim of the study was to analyze whether COVID-19 cause a delay in the diagnosis of gastric cancer patients particularly in the TNM staging of the tumor, or not. MATERIAL AND METHODS: This retrospective single-center study included the patients diagnosed with gastric cancer from March, 2019 to December 2020. The patients were divided into two groups: baseline and the pandemic groups. The following parameters were compared between the groups; demographic data, numbers of newly diagnosed patients, type of the surgery, location of the tumor, frequency of neoadjuvant treatment, ASA score, length of hospital stay, clinical staging and pathologic TNM staging. RESULTS: The mean monthly number of newly diagnosed gastric cancer patients showed a significant decline from 7.5 to 5.6 (p< .001). There were no statistically significant differences between the groups with regard to the demographic factors, except CA 19-9 levels. Patients in the pandemic group had higher both clinical and pathological T-stages (p < 0.05). CONCLUSIONS: Our study showed a decline in the number of the newly diagnosed patients with gastric cancer during the pandemic and also more patients presented with advanced stage during the pandemic period. This study showed that the pandemic causes a potential delay in the diagnosis of gastric cancer patients. KEY WORDS: Cancer surgery, COVID-19, Gastric cancer, Gastric surgery SARS-COV-2, Pandemic.

Digital Necrosis Due to Septic Embolism: An Unseen Complication of Gangrenous Cholecystitis.

Gangrenous cholecystitis is one of the most severe complications of cholelithiasis. It causes serious morbidity and mortality. The main pathology in this complication is progressive vascular insufficiency, which may lead to necrosis and perforation of the gallbladder wall. Vascular insufficiency can affect other organs besides the gallbladder. Since its symptoms are not different from that of acute cholecystitis, delayed diagnosis and treatment can cause death. Treatment is a surgical intervention as soon as the diagnosis is made. Complications such as wound infection, intra-abdominal abscess, circulatory disorders, and lung problems can be seen in the postoperative period. Embolism and necrosis in distant organs as a complication of gangrenous cholecystitis have not been reported till date. In this case, we present a patient, who developed necrosis of the fingers and toes due to septic embolism as a complication of gangrenous cholecystitis. Key Words: Cholelithiasis, Acute cholecystitis, Gangrene, Necrosis.

Duodenal Ulcer Perforation after Activated Charcoal Treatment.

Activated charcoal, having the capacity to absorb substances with its porous surface, has been used in intoxication treatment for nearly 200 years. Although live-saving, occasionally, it can lead to complications. Because of the risk of perforation during activated charcoal therapy, the integrity of the gastrointestinal tract should be checked after the procedure. In this case report, a 27-year patient, who received activated charcoal therapy after diclofenac intoxication developed duodenal ulcer perforation and charcoal peritonitis. The present case constitutes the first report of duodenal ulcer perforation after activated charcoal therapy. It should be remembered that activated charcoal, which is widely used in intoxication treatment, may cause gastrointestinal system perforation, peritonitis, adhesion, abscess formation, organ loss within the abdomen, and prolonged hospitalization. Key Words: Activated charcoal, Intoxication, Duodenal ulcer perforation.

The Role of Ca 19-9, Ca 72-4, Cea and Cholesterol Levels in Predicting Malignancy in Gallbladder Polyps.

OBJECTIVE: To determine the association of malignancy potential of gallbladder polyps with tumor markers and cholesterol levels, and at which value the presence of malignancy should be suspected. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: University of Health Sciences, Adana City training and research Hospital from December 2017 to November 2020. METHODOLOGY: Ninety patients diagnosed with gallbladder polyp by abdominal ultrasonography, were included in the study. Patients were divided into subgroups of true pseudopolyp, cholesterol-non-cholesterolpolyp, malignant-non-malignant polyp. The groups were compared in terms of age, gender, polyp size, number of polyps, preoperative total cholesterol, HDL (high-density lipoprotein), LDL (low-density lipoprotein), triglyceride, Ca 19-9 (carbohydrate antigen 19-9), Ca 72-4 (carbohydrate antigen 72-4), Cea (carcinoembryonic antigen) levels. RESULTS: In the true polyp group, polyp size, Ca 19-9, Ca 72-4 and Cea median values were significantly higher (p=0.001, p=0.029, p=0.003, and p=0.007, respectively); whereas, triglyceride levels were significantly lower compared to the pseudopolyp group (p=0.002). Polyp size was significantly lower in cholesterol polyp group compared to non-cholesterol polyp group (p= 0.032), and LDL and triglyceride medians were significantly higher (p=0.031, and p<0.001) in cholesterol group. Among the true polyps, polyp size, Ca 19-9, Ca 72-4 and Cea levels were significantly higher in adenocarcinoma group than non-malignant polyp groups (p<0.05). Cut-off values were determined as >11 mm AUC: 0.906 for size, >24.1 U/mL. AUC: 1.00 for Ca 19-9, >9.6 U/mL AUC: 1.00 for Ca 72-4, and >40 ng/mL AUC: 0.984 for CEA, respectively. CONCLUSION: Polyps larger than 11mm with high levels of CEA, Ca 72-4, Ca 19-9, evaluated together, may act as a guide for the clinician in predicting malignancy. The availability of economical and accessible parameters may allow a new algorithm to be developed in the treatment and follow-up approach of gallbladder polyps. Key Words: Gallbladder polpys, Ca 19-9 antigen, Ca 72-4 antigen, Tumor marker, Gallbladder cancer.

Inhibitory Effects of Artificial Sweeteners on Bacterial Quorum Sensing.

Despite having been tagged as safe and beneficial, recent evidence remains inconclusive regarding the status of artificial sweeteners and their putative effects on gut microbiota. Gut microorganisms are essential for the normal metabolic functions of their host. These microorganisms communicate within their community and regulate group behaviors via a molecular system termed quorum sensing (QS). In the present study, we aimed to study the effects of artificial sweeteners on this bacterial communication system. Using biosensor assays, biophysical protein characterization methods, microscale thermophoresis, swarming motility assays, growth assays, as well as molecular docking, we show that aspartame, sucralose, and saccharin have significant inhibitory actions on the Gram-negative bacteria N-acyl homoserine lactone-based (AHL) communication system. Our studies indicate that these three artificial sweeteners are not bactericidal. Protein-ligand docking and interaction profiling, using LasR as a representative participating receptor for AHL, suggest that the artificial sweeteners bind to the ligand-binding pocket of the protein, possibly interfering with the proper housing of the native ligand and thus impeding protein folding. Our findings suggest that these artificial sweeteners may affect the balance of the gut microbial community via QS-inhibition. We, therefore, infer an effect of these artificial sweeteners on numerous molecular events that are at the core of intestinal microbial function, and by extension on the host metabolism.

Littoral Cell Angioma of the Spleen presenting with Thrombocytosis and Splenic Infarct.

Littoral cell angioma is a non-hematologic vascular neoplasm originating from littoral cells lining the splenic red pulp. The diagnosis is usually made incidentally in splenectomy materials. It is often associated with anemia and thrombocytopenia, indicative of hypersplenism. We, herein present a case of symptomatic littoral cell angioma in a 32-year female, presumed to be accompanied by a hematologic malignancy manifesting with splenic infarct and thrombocytosis. Key Words: Littoral cell angioma, Splenic infarct, Thrombocytosis.

Assessing the Molecular Targets and Mode of Action of Furanone C-30 on Pseudomonas aeruginosa Quorum Sensing.

Quorum sensing (QS), a sophisticated system of bacterial communication that depends on population density, is employed by many pathogenic bacteria to regulate virulence. In view of the current reality of antibiotic resistance, it is expected that interfering with QS can address bacterial pathogenicity without stimulating the incidence of resistance. Thus, harnessing QS inhibitors has been considered a promising approach to overriding bacterial infections and combating antibiotic resistance that has become a major threat to public healthcare around the globe. Pseudomonas aeruginosa is one of the most frequent multidrug-resistant bacteria that utilize QS to control virulence. Many natural compounds, including furanones, have demonstrated strong inhibitory effects on several pathogens via blocking or attenuating QS. While the natural furanones show no activity against P. aeruginosa, furanone C-30, a brominated derivative of natural furanone compounds, has been reported to be a potent inhibitor of the QS system of the notorious opportunistic pathogen. In the present study, we assess the molecular targets and mode of action of furanone C-30 on P. aeruginosa QS system. Our results suggest that furanone C-30 binds to LasR at the ligand-binding site but fails to establish interactions with the residues crucial for the protein's productive conformational changes and folding, thus rendering the protein dysfunctional. We also show that furanone C-30 inhibits RhlR, independent of LasR, suggesting a complex mechanism for the agent beyond what is known to date.

Correlation of Breast Cancer Subgroups and Axillary Metastases with 18F-FDG PET/CT and the Contribution of 18F-FDG PET/CT in the Management of the Axilla.

OBJECTIVE: To investigate whether breast and axilla maximum standard uptake (SUVmax) values contribute to the treatment approach in breast cancer subgroups. STUDY DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: University of Health Sciences/Adana City Training and Research Hospital, Turkey, from April 2017 to September 2019. METHODOLOGY: Ninety patients, operated for early breast cancer, were examined histopathologically and demographically. Those patients were divided into subgroups, according to the St. Gallen consensus. Breast and axillary SUVmax uptakes of these subgroups were determined using (Fluorine18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). These values were compared with postoperative pathology results Results: The triple negative group had the highest values and the Luminal B pos (+) group had the lowest values, when the mean values of breast and axilla SUVmax were compared. Axilla SUVmax value in those with metastatic lymph node was 1.939 times higher than those without it. The cut-off value of SUVmax value of the axillary lymph nodes was found to be 1.1 in distinguishing metastatic from non-metastatic. CONCLUSION: As the biological aggressiveness of tumor increased, SUVmax values increased in parallel. As a result, SUVmax values guided in determining the presence of axillary metastasis and treatment strategy. Key Words: Breast cancer, 18F-FDG PET/ CT, SUVmax values, Tumor subgroups, Axilla.

Evaluating the feasibility of performing elective gastrointestinal cancer surgery during the COVID-19 pandemic: An observational study with 60 days follow-up results of a tertiary referral pandemic hospital.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has interfered with the treatment algorithm for patients with gastrointestinal (GIS) cancer, resulting in deferral of surgery. We presented the outcomes of our patients to evaluate whether surgery could be safely performed and followed-up without delaying any stage of GIS cancer during the pandemic. METHODS: This was an observational study of 177 consecutive patients who underwent elective GIS cancer surgery between March 11 and November 1, 2020. They were assessed regarding their perioperative and 60 days follow-up results for either surgical or COVID-19 status. Morbidity was determined according to the Clavien-Dindo classification (CDC). Continuous and categorical data were presented as median ± SD and number with percentage (%), respectively. RESULTS: The study included 44 gastric, 33 pancreatic, 40 colon, and 59 rectal cancer patients. All patients underwent surgery and received neo/adjuvant treatments without delay. The overall morbidity (CDC grade II-IV) and mortality rates were 10.1% and 3.9%, respectively. None of the patients or medical staff were infected with COVID-19 during the study period. CONCLUSION: GIS cancer surgery can be safely performed even within a pandemic hospital if proper isolation measures can be achieved for both patients and health workers. Regardless of the tumor stage, surgery should not be deferred, depending on unstandardized algorithms.

Comparison of hemostatic efficacy of topical Ankaferd Blood Stopper on heparinized and nonheparinized rats in bleeding related to liver injury.

PURPOSE: In this study, hemostatic efficacy of Ankaferd Blood Stopper (ABS), a new generation hemostatic agent, was compared in the presence of heparin effect. METHODS: Forty-eight Wistar albino rats were divided into two main groups as heparinized and nonheparinized, and these two main groupswere divided into six subgroups as control, Surgicel and ABS (n = 8). Grade 2 liver injury was performed on rats as standard. All groups were compared in terms of weight, laceration surface area, prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalized ratio (INR), bleeding time, bleeding amount, hemoglobin (Hb) levels, macroscopic and microscopic reactions to the agent used. RESULTS: Whereas there was no statistically significant difference between weight, laceration surface area, PT, INR and preoperative Hb values in the heparinized and nonheparinized groups, postoperative Hb, bleeding time, bleeding amount and aPTT values were statistically different (p < 0.05). In the heparin-hemostat interaction, the ABS group had the lowest bleeding in the heparinized group in terms of the amount of bleeding compared to the control and Surgicel groups (F = 0.764; p = 0.047). In macroscopic and microscopic comparison, there was no difference between the groups in terms of cell necrosis andfresh bleeding (p > 0.05), it was found that the Surgicel group had statistical significantly higher reaction scores (p < 0.05) than the other groups in terms of other parameters. CONCLUSIONS: Ankaferd Blood Stopper can be safely and effectively used in surgical practice and in patients with additional diseases requiring heparinization, since it causes minimal reaction in the liver and decreases the amount of bleeding especially in the heparinized group.

Comparison of hemostatic efficacy of topical Ankaferd Blood Stopper on heparinized and nonheparinized rats in bleeding related to liver injury

ABSTRACT Purpose: In this study, hemostatic efficacy of Ankaferd Blood Stopper (ABS), a new generation hemostatic agent, was compared in the presence of heparin effect. Methods: Forty-eight Wistar albino rats were divided into two main groups as heparinized and nonheparinized, and these two main groupswere divided into six subgroups as control, Surgicel and ABS (n = 8). Grade 2 liver injury was performed on rats as standard. All groups were compared in terms of weight, laceration surface area, prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalized ratio (INR), bleeding time, bleeding amount, hemoglobin (Hb) levels, macroscopic and microscopic reactions to the agent used. Results: Whereas there was no statistically significant difference between weight, laceration surface area, PT, INR and preoperative Hb values in the heparinized and nonheparinized groups, postoperative Hb, bleeding time, bleeding amount and aPTT values were statistically different (p < 0.05). In the heparin-hemostat interaction, the ABS group had the lowest bleeding in the heparinized group in terms of the amount of bleeding compared to the control and Surgicel groups (F = 0.764; p = 0.047). In macroscopic and microscopic comparison, there was no difference between the groups in terms of cell necrosis andfresh bleeding (p > 0.05), it was found that the Surgicel group had statistical significantly higher reaction scores (p < 0.05) than the other groups in terms of other parameters. Conclusions: Ankaferd Blood Stopper can be safely and effectively used in surgical practice and in patients with additional diseases requiring heparinization, since it causes minimal reaction in the liver and decreases the amount of bleeding especially in the heparinized group.

The effect of activated protein C in the experimental disseminated intravascular coagulation model formed by lipopolysaccharide infusion.

PURPOSE: In this experimental study, activated protein C (APC), which has anticoagulant, antithrombotic, profibrinolytic, anti-inflammatory and antiapoptotic properties, was used to prevent coagulopathy in a disseminated intravascular coagulation (DIC) model formatted with lipopolysaccharide (LPS) infusion. METHODS: Twenty-five Wistar albino rats weighting 280 - 320 g each were used. They were randomly divided into three groups: sham, control and study groups. To sham group (n = 5), only normal saline was infused. To control (n = 10) and study groups (n = 10), 30 mg/kg LPS was infused for 4 h from femoral vein. After LPS infusion, 100 µg/kg recombinant APC was given during 4 h in study group. Eight hours later, blood samples were taken from abdominal aorta and the animals sacrificed. From these samples, platelet, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and D-dimer levels were studied. RESULTS: Platelet counts and fibrinogen levels were significantly lower in control and study groups than sham group (p < 0.05). The PT, aPTT and D-dimer levels were significantly higher in control and study groups than in sham group (p < 0.05). When comparing control and study groups, platelet counts were not statistically different (p = 0.36). However, the difference of the fibrinogen levels was significant between these groups (p = 0.0001). While PT and aPTT were longer in the study group compared to the control group (p < 0.05), D-dimer levels were lower in the study group than in control (p = 0.0001). CONCLUSION: Use of APC can prevent hypercoagulation and consumption coagulopathy in the DIC as a result of correcting hematological parameters other than prolongation of coagulation time.

Evaluation of the Mechanical Properties of Anorectal Tissues and Muscles by Shear Wave Elastography in Anal Fissure Disease.

OBJECTIVE:  To evaluate the mechanical properties of the tissues and muscles in the anal region with the shearwave elastography for anal fissure etiology. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Adana City Training and Research Hospital, Turkey, from March2019 to March 2020. METHODOLOGY: In this study, 30 patients (fissure group), who were diagnosed with anal fissure in the outpatient clinic; and 20 patients (control group), who did not have any problem in anal examination were included. The anorectal tissues and muscles mechanical properties(elasticity,compliance and stiffness) were compared with the shear wave elastography values.Fissure area,internal anal sphincter,external anal sphincter and levator ani muscles elastographic measurements was performed with 5-18 MHzin lithotomy position, at rest and with Valsalva maneuver. RESULTS: In elastographic measurement of fissure area (fissure) and normal anorectal tissue (control, AFE); control group values were significantly higher than the fissure group values (p<0.001, and padj <0.001, respectively). Control group valuesof internal anal sphincter in rest and Valsalva maneuver (IAS-R, and IAS-V, respectively) were significantly higher than the fissure group values (p<0.001, padj< 0.001, and p<0.001,  padj <0.001, respectively). There was no significant difference between the elastographic measurement values in rest and valsalva maneuver of the external anal sphincter (EAS-R and EAS-V) (p>0.05). Elastographic measurement values of levator ani muscle (LAM) resting state; were significantly higher in thefissure group than the control group (p<0.001, and padj <0.001, respectively). Elastographic cut-off values that differentiate the fissure group from control group were found to be ≤1kPa forAFE group, ≤44 kPa forIAS-R, ≤0.4kPa forIAS-V,and >11kPa for LAM,respectively. Conclusion: In anal fissure disease, tissues mechanical properties measured by shear wave elastography showed increased tissue stiffness, which may be added to etiology of this disease. Key Words: Anal fissure, Ultrasonography, Shear wave elastography, Anal sphincter, Tissue elasticity, Tissue stiffness.

Anti-Quorum Sensing Activity of Stevia Extract, Stevioside, Rebaudioside A and Their Aglycon Steviol.

Governments are creating regulations for consumers to reduce their sugar intake, prompting companies to increase the ratio of artificial sweeteners in their products. However, there is evidence of some deleterious effects ascribed to the aforementioned synthetic agents and therefore consumers and food manufacturers have turned their attention to natural dietary sweeteners, such as stevia, to meet their sweetening needs. Stevia is generally considered safe; however, emerging scientific evidence has implicated the agent in gut microbial imbalance. In general, regulation of microbial behavior is known to depend highly on signaling molecules via quorum sensing (QS) pathways. This is also true for the gut microbial community. We, therefore, evaluated the possible role of these stevia-based natural sweeteners on this bacterial communication pathway. The use of a commercial stevia herbal supplement resulted in an inhibitory effect on bacterial communication, with no observable bactericidal effect. Purified stevia extracts, including stevioside, rebaudioside A (Reb A), and steviol revealed a molecular interaction, and possible interruption of Gram-negative bacterial communication, via either the LasR or RhlR receptor. Our in-silico analyses suggest a competitive-type inhibitory role for steviol, while Reb A and stevioside are likely to inhibit LasR-mediated QS in a non-competitive manner. These results suggest the need for further safety studies on the agents.

Effect of Anastomosis Technique on Pancreatic Fistula Formation in Proximal Pancreaticoduodenectomy.

OBJECTIVE: To find out the association between the pancreatic fistula development and the pancreaticoduodenectomy anastomosis technique performed in three different ways; namely, telescopic pancreatojejunostomy (PJ), ducto-mucosal Wirsungo jejunostomy (WJ), and Peng's variant of the telescopic technique. STUDY DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: Izmir Katip Celebi Universitesi Hospital, Turkey, from January 2011 to January 2018. METHODOLOGY: A total of 144 proximal pancreaticoduodenectomy procedures were performed at the study centre. Patients' data was obtained from the outpatient files and hospital information system, retrospectively; and divided into three groups according to the pancreatic anastomosis techniques. All three groups were compared in terms of eight parameters. Preoperative parameters were age, gender, and serum direct bilirubin values; whereas, postoperative parameters were pathology, pancreatic fistula, drain amylase, serum albumin value and early mortality. RESULTS: All variables by anastomosis type belonging to three groups differed for fistula rates (p=0.384), pathology types (p=0.142), preoperative bilirubin (p=0.631) and postoperative albumin (p=0.516) levels, early mortality (p=0.242) parameters without reaching statistical significance (p>0.05); however, the low anastomosis leak rates in Peng's technique were remarkable. POPF (post-operative pancreatic fistula) developed in 34% patients under 60 years vs. 17.6% patients over 60 years of age (p=0.029); and 13.7% females vs. 29.9% of male patients (p=0.032). CONCLUSION: No factors other than age and gender were found to be significant alone in the development of pancreatic fistula after proximal pancreaticoduodenectomy. Key Words: Postoperative pancreatic fistula, Pancreaticoduodenectomy, Pancreatojejunostomy, Telescopic pancreatojejunostomy (PJ), Ducto-mucosal Wirsungo jejunostomy (WJ), Peng's telescopic technique.

The effect of activated protein C in the experimental disseminated intravascular coagulation model formed by lipopolysaccharide infusion

Abstract Purpose: In this experimental study, activated protein C (APC), which has anticoagulant, antithrombotic, profibrinolytic, anti-inflammatory and antiapoptotic properties, was used to prevent coagulopathy in a disseminated intravascular coagulation (DIC) model formatted with lipopolysaccharide (LPS) infusion. Methods: Twenty-five Wistar albino rats weighting 280 - 320 g each were used. They were randomly divided into three groups: sham, control and study groups. To sham group (n = 5), only normal saline was infused. To control (n = 10) and study groups (n = 10), 30 mg/kg LPS was infused for 4 h from femoral vein. After LPS infusion, 100 µg/kg recombinant APC was given during 4 h in study group. Eight hours later, blood samples were taken from abdominal aorta and the animals sacrificed. From these samples, platelet, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and D-dimer levels were studied. Results: Platelet counts and fibrinogen levels were significantly lower in control and study groups than sham group (p < 0.05). The PT, aPTT and D-dimer levels were significantly higher in control and study groups than in sham group (p < 0.05). When comparing control and study groups, platelet counts were not statistically different (p = 0.36). However, the difference of the fibrinogen levels was significant between these groups (p = 0.0001). While PT and aPTT were longer in the study group compared to the control group (p < 0.05), D-dimer levels were lower in the study group than in control (p = 0.0001). Conclusion: Use of APC can prevent hypercoagulation and consumption coagulopathy in the DIC as a result of correcting hematological parameters other than prolongation of coagulation time.

Gallstone ileus with evident forchet sign:case report.

INTRODUCTION: Gallstone ileus (GSI) is a rare complication of cholelithiasis (gallbladderstone), which may lead to obstruction of the small intestine. Particularly, computerized tomographic (CT) imaging method and special findings in these images help diagnosing of gallstone ileus. Treatment of this disease is surgery, surgery involves cholecystectomy + fistula repair + enterolitotomy, but it is controversial to perform cholecystectomy with enterolitotomy and fistula repair in the same session. PRESENTATION OF CASE: A 75-year-old male patient consulted to the emergency department with the complaints of nausea and vomiting. In the examinations of the patient, bilienteric fistula and gallstones that impacted in the jejunum leading to obstruction were observed in abdominal CT images of the patient who has ileus. The patient was evaluated as gallstone ileus. In addition, on tomographic images significant Forchet sign and Rigler's triad images were viewed which were pathognomonic for gallstone ileus and did not have images as clear as in our case in the literature search. Laparotomy was performed on the patient due to the fact that he was elderly and the duration of anesthesia was wanted to be kept short and stone was extracted by enterolitotomy. Cholecystectomy and fistula repair were left for another session because of gallbladder and surrounding tissues were edematous. The patient was discharged with full recovery on the 6th post-operative day. DISCUSSION-CONCLUSION: As well as this disease is a rare cause of mechanical bowel obstruction, it is mostly seen in elderly patients. The most sensitive and specific imaging method in diagnosis is contrast-enhanced abdominal computerized tomography. In the tomographic images, especially the Rigler's triad, Forchet sign and Petren sign are pathognomonic for gallstone ileus.

The Relevance of Glutathione Reductase Inhibition by Fluoxetine to Human Health and Disease: Insights Derived from a Combined Kinetic and Docking Study.

Glutathione reductase (GR) is a homodimeric enzyme playing an important role in the regeneration of the central antioxidant molecule reduced glutathione (GSH) from oxidized glutathione (GSSG) at the expense of a molecule of NADPH. GSH scavenges and eliminates superoxide and hydroxyl radicals non-enzymatically or serves as an electron donor for several enzymes. Fluoxetine (FLU), a selective serotonin reuptake inhibitor, is widely prescribed in the treatment of major depressive disorder. Here, using enzyme kinetic studies and molecular docking simulations, we aimed at disclosing the mechanistic and structural aspects of the interaction between GR and FLU. Affecting enzyme activity in a dose-dependent manner, FLU was shown to be a moderately potent (IC50 = 0.88 mM) inhibitor of GR. When the variable substrate was GSSG, the type of inhibition was linear mixed-type competitive (Ki = 279 ± 32 µM; α = 5.48 ± 1.29). When the variable substrate was NADPH, however, the type of inhibition was non-competitive (Ki = 879 ± 82 µM). The observed difference in inhibition types was attributed to the binding of FLU in the large intermonomer cavity of GR, where it hampered catalysis and interfered with substrate binding. Overall, although it is anticipated that long-term use of FLU leads to acquired GR deficiency, the inhibitory action of FLU on GR may be therapeutically exploited in anti-cancer research.