Favipiravir Protects Enterocytes From Cell Death After Inflammatory Storm.

Over the past years, inflammatory bowel disease (IBD) treatment has become more targeted, anticipating the use of immune-modifying therapies at an earlier stage. During the treatment process prevention and management of viral infections hold significant importance. The protective role of favipiravir on enterocytes which are affected by inflammation is still unknown. We aim to analyze the effects of favipiravir on enterocytes after an inflammatory condition. We conducted a 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay to assess the cytotoxicity of favipiravir on intestinal epithelioid cells (IEC-6). To mimic the inflammation model in cell culture conditions, we exposed IEC-6 cells to tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). The cells were categorized into four groups: control, inflammation model, application of favipiravir before inflammation (prophylactic), and application of favipiravir after inflammation (treatment). We assessed the presence and distribution of caspase 1, caspase 3, interleukin 6 (IL6), interleukin 8 (IL8), mixed lineage kinase domain-like protein (MLKL), receptor-interacting protein kinase 1 (RIPK1), and TNF-α using indirect immunoperoxidase staining. TNF-α and IL8 levels were analyzed with enzyme-linked immunosorbent assay (ELISA) in a culture medium. Caspase 1 was observed to be strong (+++) in the treatment group and weak (+) in the prophylactic group compared to the inflammation group. Caspase 3 was weak (+) in the inflammation group, and it was strong (+++) in the prophylactic and treatment group, the increase in the treatment group was significant. Therefore administering favipiravir before inducing inflammation appears to control the inflammatory caspase pathway in intestinal enterocytes, protecting them from inflammatory responses, while the caspase 3-dependent apoptotic pathway may not be active in enterocytes during inflammation. IL6 and IL8 were negative (-) in control, IL6 was weak (+) in inflammation and favipiravir treated groups; IL8 increased significantly in favipiravir groups compared to control and inflammation groups. Consequently, favipiravir may trigger IL6 release, initiating the inflammatory pathway and potentially enhancing IL8 interactions with other cytokines. TNF-α immunoreactivity was strong (+++) in the inflammation group, while it was moderate (++) in favipiravir-administered groups. MLKL immunoreactivity was strong (+++) in all groups, RIPK1 was weak (+) in control, strong (+++) in the inflammation and treatment group, moderate (++) in the prophylactic group, and the increase in inflammation and treatment group was significant compared to control. Our findings suggest that in the treatment group, necroptosis was triggered by increased MLKL and RIPK1, key players in inflammation and cell death. After immunocytochemical evaluation, our findings suggest that, after the onset of inflammation, favipiravir may play a role in cell death by increasing necroptosis rather than apoptosis.

Does Preoperative Anxiety Decrease with BATHE Method? A Prospective Randomized Study.

INTRODUCTION: Preoperative anxiety due to anesthesia is a common situation and decreases with preoperative evaluation. The aim of this study is to determine whether utilization of BATHE method further decreases the anxiety scores of patients who are evaluated at an anesthesia clinic for preoperative examination. METHODS: The patients were randomized into "BATHE" and "Control" groups by using the closed envelope technique. State-Trait Anxiety Inventory (STAI) scores were recorded as entrance STAI for all patients. During preoperative evaluation, BATHE method was applied to the BATHE Group whereas it was not applied to the Control Group. Post-examination, STAI scores were recorded as exit STAI and the patients were later asked questions about their contentment. RESULTS: Data of 463 patients were included in the analysis. Demographic data was similar in the groups. In both groups the exit STAI scores (BATHE: 34.27±10.30, Control: 34.90±9.54) were lower in comparison to the entrance STAI scores (BATHE: 38.21±9.86, Control: 37.09±9.93). The mean gap between the entrance STAI and exit STAI scores of the BATHE (3.94±6.05) and Control groups (2.19±6.14) were statistically significant (p<0.001). CONCLUSION: Utilization of BATHE method decreases the anxiety scores of preoperative patients to a greater extent, as measured by STAI index, in comparison to standard preoperative evaluation.

The effects of tramadol on cancer stem cells and metabolic changes in colon carcinoma cells lines.

Opioids are widely used in the treatment of cancer related pain. They mainly exert their effects on opioid receptors. The most common opioid in the treatment of pain is morphine. Previous studies show that they may have effects on cancer cell behavior. These may include apoptosis, angiogenesis, invasion, inflammation and immune reactions. Tramadol, also an opioid is widely used in the treatment of cancer pain and is not well studied in cancer behavior. We aimed to investigate the effects of tramadol on cancer stem cells and metabolic changes in colon carcinoma cells. We used Colo320 (ATCC, CCL-220), Colo741 (ECACC, 93052621) and HCT116 (ATCC, CCL-247) colon cancer cell lines. CD133 was considered colon cancer stem cell marker and used to sort CD133+ and CD133- cells by magnetic cell sorting. MTT (mitochondria-targeted therapeutics) technique was used to detect tramadol's cytotoxic effect on cells in the study groups. Cells were treated with 1 mg/kg, 1.5 mg/kg and 2 mg/kg tramadol for 24 h at 37 °C and 5% CO2.Caspase-3, Ki-67, Bcl-2 and VGEF distributions were performed using indirect immunoperoxidase staining for immunohistochemical analysis. The study showed that tramadol has triggering effect on apoptosis in Colo320 colon cancer stem cells.

Intragastric balloon treatment for obesity: prospective single-center study findings.

BACKGROUND: The intragastric balloon (IGB) procedure is an obesity treatment. METHODS: A BioEnteric IGB was used in 33 patients between February 2006 and February 2009. RESULTS: Of the 31 patients, 19 were female (61.3%). Mean age was 35.48 +/- 9.31 years. Following intravenous sedation, the balloon was inserted and inflated under direct vision by using saline (600 ml) and methylene blue (10 ml) solution. Average weight and mean BMI scores were as follows: 119.34 +/- 22.64 (range 80-170) kg and 41.84 +/- 8.28 (range 30-63.2) kg/m(2). Mean weight and BMI were measured as 104.31 +/- 21.33 (range 64-151) kg and 36.43 +/- 7.36 (range 26-52) kg/m(2) 6 months after the index procedure. Percent of excess weight loss (%EWL) and percent of excess body mass index loss (%EBMIL) were as follows: 29.16 +/- 15.99% (range 0.00-56.91%) and 35.45 +/- 19.46% (0-75.2%), respectively. All patients lost weight constantly for the 6-month period. Patients showed statistically significant weight and BMI losses for the first 3-month period but these decrements reached a plateau between the 4th and 6th month. Weight loss was not statistically significant during the second 3-month period. Few patients had mild complaints following balloon insertion; there was no balloon intolerance. CONCLUSIONS: IGB is safe and effective for short-term weight reduction in obese patients. Weight reduction during the second half of the treatment period needs closer follow-up.

Timing of levosimendan in cardiac surgery.

OBJECTIVE: Levosimendan (LS) is a new inodilator agent that improves cardiac contractility by increasing the sensitivity of troponin C to calcium, which usage in cardiac surgery has been growing in the recent years. We aimed to determine the best timing of the administration of LS in high-risk patients who underwent cardiovascular surgery. METHODS: Fifteen patients were evaluated retrospectively who have left ventricular dysfunction, underwent open-heart surgery and were applied LS in different phases of operation. Patients were divided into 3 groups according to timing of LS. Levosimendan infusion (0. 1 microg-1kg-1min) was applied after the induction of anaesthesia (n=5) (Group 1), during the pump removal period (n=5) (Group 2) and in postoperative period (n=5) (Group 3). Demographic data, operative characteristics, mean arterial pressure (MAP), mean pulmonary arterial pressure (MPAP), pulmonary wedge capillary pressure (PWCP), cardiac index (CI), inotropic agent consumption, postoperative urine output, lactate levels of groups were compared between before and after LS treatment. Data were evaluated by Fisher exact, Kruskal-Wallis, Mann-Whitney U and Wilcoxon rank tests. RESULTS: In all patients, urine output was satisfactory 24 hours after LS application. There was a significant increase in CI of all 3 groups (p=0.04). Also, there was a significant decrease in PCWP of all 3 groups before and after LS (p=0.04). There was a significant decrease in MPAP in Group 2 and 3 (p=0.04). Twenty- four hours after LS application, whereas all inotropic agents could be stopped in Group 1 and 2, in Group 3 inotropic infusion (dopamine [10 microg-1kg-1min (5-17.5)], dobutamine [15 microg-1kg-1min (5-20)] and adrenaline [0.4 microg-1kg-1min (0.15-0.65)]) couldn't be stopped (p=0.007). During postoperative period, in Groups 1 and 2 one case from each required intraaortic balloon pump, while in Group 3 four patients were applied intraaortic balloon pump (p=0.08). CONCLUSION: According to our experience, LS is effective in high-risk cases during cardiac surgery, especially during the intra-operative and pump removal periods;however, no successful outcomes were observed during the post-operative period. As a result, case selection and timing should be performed well when using LS.

The effects of an epidural infusion of ropivacaine versus saline on sensory block after spinal anesthesia.

BACKGROUND AND OBJECTIVES: Several investigators have described the effect of bolus injections on sensory block during combined spinal epidural anesthesia. This study investigates the effects of the immediate epidural infusion of 0.2% ropivacaine versus 0.9% saline on spinal anesthesia. METHODS: Forty-four patients undergoing partial hip replacement were randomly assigned to 2 groups, receiving epidural infusion of 0.2% ropivacaine 10 mL/h (group R, n = 22) or 0.9% NaCl 10 mL/h (group S, n = 22), immediately after spinal anesthesia with 7.5 mg 0.5% hyperbaric bupivacaine. Postoperative analgesia was provided in both groups using a ropivacaine patient-controlled epidural analgesia technique. Sensory block, motor block, postoperative pain scores, ropivacaine consumption, and patient satisfaction were recorded. RESULTS: There was no difference between the 2 groups in the characteristics of the sensory block. The duration of motor block was prolonged in group R (312 +/- 95 minutes vs 198 +/- 78 minutes; P < .001). Postoperative pain scores and 24-hour ropivacaine consumption were similar among groups. Demand/delivery ratio was 1.6 in group R and 3.5 in group S (P = .048). A significantly higher number of patients in group R described their satisfaction as excellent (20 patients vs 6 patients; P < .001). CONCLUSIONS: Epidural infusion of ropivacaine 0.2% initiated immediately after spinal anesthesia prolonged the regression of motor block but not the regression of sensory block when compared with saline infusion.

Does preoperative hydration affect postoperative nausea and vomiting? A randomized, controlled trial.

BACKGROUND: It has been suggested that relative hypovolemia due to overnight fasting may result in postoperative nausea and vomiting (PONV). The aim of this study was to investigate the effect of preoperative and intraoperative hydration (the necessary amount of fluid preoperatively to cover the fluid deficit) on PONV. MATERIALS AND METHODS: Two hundred and ten consecutive patients who underwent elective laparoscopic cholecystectomy with The American Society of Anesthesiologists (ASA)-I physical statuses were studied prospectively. The patients were randomly assigned to one of two groups, each having 104 patients. Group 1 received intraoperative volume replacement, but Group-II received preoperative volume replacement. Postoperative antiemetic efficacy was assessed by the ratio of the patients that require an antiemetic over the whole group. RESULTS: The PONV was significantly less detected in the preoperative replacement group (48% in Group 2) than the intraoperative one (64% in Group 1) (P = 0.019). CONCLUSIONS: PONV was reduced when the fluid deficit was replaced preoperatively.

Reversal of prilocaine epidural anesthesia using epidural saline or ringer's lactate washout.

BACKGROUND AND OBJECTIVES: Several investigators have described the phenomena of epidural saline washout using bolus injections. This study was designed to determine whether epidural block could be reversed more effectively by infusion of crystalloid solutions via the epidural catheter. METHODS: One hundred male patients scheduled for outpatient surgery were enrolled in this study. After 30 min of 2% prilocaine epidural anesthesia, patients were randomly assigned to receive 45 mL of study solution as follows: (1) normal saline bolus (group NSB); (2) Ringer's lactate bolus (group RLB); (3) normal saline infusion (group NSI); (4) Ringer's lactate infusion (group RLI). Patients in the control group received no washout fluid. Motor, sensory blockade and side effects were compared among 5 groups. Ambulation time is defined as the recovery time. RESULTS: In the control group, ambulation time (139 +/- 15 min) was significantly longer than in the washout groups (NSB 90 +/- 10, RLB 88 +/- 10, NSI 85 +/- 8, RLI 91 +/- 6 minutes) (P < .001). Two-segment sensory regression time in the control group (86 +/- 15 min) was significantly longer than in groups NSB, RLB, NSI and RLI (55 +/- 8, 51 +/- 4, 58 +/- 8, and 53 +/- 10 minutes, respectively) (P < .001). CONCLUSIONS: We concluded that a more rapid recovery of motor and sensory blockade in patients undergoing epidural anesthesia may be achieved by the use of an epidural washout with either bolus or infusion of 45 mL normal saline or Ringer's lactate.