The Effect of Preprocedural Low-Dose Ketamine for Pain and Anxiety in Patients during Thoracic Epidural Catheterization.

Background and Objectives: Thoracic epidural catheterization (TEC) can be both uncomfortable and fearful for patients when performed awake with the thought that the procedure may be painful. The aim of this study was to assess the effect of low-dose intravenous ketamine administration on pain and anxiety during the TEC procedure. Materials and Methods: Sixty patients were randomly divided into two groups to receive intravenous (IV) placebo (Group P) and IV low-dose (0.15 mg/kg) ketamine (LDK) (Group K) 3 min before the procedure in a double-blind manner. A visual analog scale (VAS) was used to measure anxiety (VAS-A) and pain (VAS-P) scores. Vital parameters were monitored before premedication (T1), 20 min after premedication (T2), during skin anesthesia (T3), during TEC (T4), and 5 min after TEC (T5). VAS-A values were recorded at T1, T3, T4, and T5 periods, and VAS-P levels were noted at T3, T4, and T5 periods. Results: During TEC (T4), both VAS-P and VAS-A were significantly lower in Group K (p < 0.001). The mean VAS-A value was 10.6 mm lower, and the mean VAS-P value was 9 mm lower in Group K than in Group P at the T4 time point. Additionally, the mean VAS-P value was 7.7 mm lower in Group K compared to Group P at the T3 time point (p < 0.001). Both groups showed a statistically significant difference in VAS-A measurements when compared at their respective time points (p < 0.001). However, only Group P demonstrated a statistically significant difference in VAS-P measurements (p < 0.001). VAS-P values remained stable in Group K. The number of patients who did not recall the procedure was significantly higher in Group K (p < 0.001). Furthermore, the number of patients who would consent to the same procedure in the future was significantly higher in Group K (p = 0.007). Conclusions: A preprocedural LDK (0.15 mg/kg) can effectively prevent anxiety and pain experienced by patients during the TEC procedure. Administration of LDK may provide a more comfortable procedure process without causing ketamine-induced side effects (hemodynamic, respiratory, and psychological).

A stability indicating RP-HPLC method for determination of the COVID-19 drug molnupiravir applied using nanoformulations in permeability studies.

Antiviral drugs have gained much more attention in recent years due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and many drug candidates are currently under investigation in order to end pandemic. Molnupiravir, a prodrug of the synthetic nucleoside derivative N4-hydroxycytidine, is one of the promising candidates for SARS-CoV-2 treatment. In this study, a RP-HPLC method was developed for the determination of Molnupiravir and applied for in vitro permeability studies of self-emulsifying drug delivery system (SEDDS) formulations using Caco-2 cell line. Discovery® HS C18 Column (75 ×4.6 mm, 3 µm) was used at 30 °C. Isocratic elution was performed with ACN:water (20:80 v/v) mixture. The flow rate was 0.5 mL/min and UV detection was at 240 nm. Molnupiravir eluted within 5 min. Molnupiravir was exposed to thermal, photolytic, hydrolytic, and oxidative stress conditions. Peak homogeneity data of Molnupiravir in the stressed samples peak obtained using photodiode array detector, in the stressed sample chromatograms, demonstrated the specificity of the method for their estimation in presence of degradants. The developed method was validated according to the International Council for Harmonisation (ICH) guidelines and found to be linear within the range 0.1-60.0 µg/mL. The method was simple, rapid, selective, sensitive, accurate, precise, robust and rugged. Thus, it was applied successfully for permeability quantitation of Molnupiravir in nanoformulations. The apparent permeability of Molnupiravir in SEDDS formulations, which have droplet size under 350 nm, was calculated as 3.20 ± 0.44 × 10-6 cm/s.

Resveratrol Enhances Apoptotic and Oxidant Effects of Paclitaxel through TRPM2 Channel Activation in DBTRG Glioblastoma Cells.

Numerous studies have reported a strong association between increased production of reactive oxygen species (ROS) and the pathobiology of several diseases, and cancer in particular. Therefore, manipulation of cellular oxidative stress levels represents an important therapeutic target. Recently, resveratrol (RESV), a naturally occurring phytochemical, has been shown to sensitize several cell lines to the anticancer effects of other chemotherapeutic agents, including paclitaxel (PAX). However, the molecular mechanisms of action of RESV through oxidative sensitive TRPM2 channel activation remain unclear. The aim of this study was to evaluate the effect of combination therapy of RESV and PAX on activation of TRPM2 in DBTRG glioblastoma cells. DBTRG cells were divided into four treatment groups: control, RESV (50 µM), PAX (50 µM), and PAX + RESV for 24 hours. Our data shows that markers for apoptosis, mitochondrial membrane depolarization and mitochondrial function, intracellular steady-state ROS levels, caspase 3 activity, TRPM2 current density, and Ca2+ florescence intensity were significantly increased in DBTRG cells following treatment with PAX and RESV, respectively, although cell viability was also decreased by these treatments. These biochemical markers were further increased to favor the anticancer effects of PAX in DBTRG cells in combination with RESV. The PAX and RESV-mediated increase in current density and Ca2+ florescence intensity was decreased with a TRPM2 blocker. This suggests that for this combination therapy to have a substantial effect on apoptosis and cell viability, the TRPM2 channel must be stimulated.

Comparison of the effects of fentanyl, remifentanil, and dexmedetomidine on neuromuscular blockade.

PURPOSE: The aim of our study was to compare the effects of fentanyl, remifentanil, and dexmedetomidine on neuromuscular blockade under sevoflurane anesthesia. METHODS: Eighty-four patients were randomized to fentanyl, remifentanil, and dexmedetomidine groups. In the fentanyl group, fentanyl 1.5 µg/kg was given before induction of anesthesia, and additional 50-µg boluses were administered. In the remifentanil group, the initial dose of remifentanil 1 µg/kg was infused in 10 min before induction and 0.1 µg/kg/min infusion was continued during anesthesia. In the dexmedetomidine group, the initial dose of dexmedetomidine 1 µg/kg was infused in 10 min before induction and 1 µg/kg/h infusion was continued during anesthesia. Heart rate, blood pressure, SpO(2), EtCO(2), and TOF (train-of-four) values of all patients were monitored during anesthesia. Times to reach TOF 0 and TOF 25% and intubation quality were recorded. RESULTS: T (0) times and quality of intubation were found to be similar among the groups. T (25) time was found to be significantly longer in the dexmedetomidine group than in the fentanyl and remifentanil groups. CONCLUSION: Dexmedetomidine infusion increased the duration of neuromuscular blockade with vecuronium during general anesthesia. In addition to analgesic and sedative effects, dexmedetomidine may enhance the duration of neuromuscular blockade and may be used as an adjuvant anesthetic during general anesthesia.

Massive upper gastrointestinal bleeding from pure metastatic choriocarcinoma in patient with mixed germ cell tumor with subclinical intestinal metastasis.

Although testicular germ cell tumors have become curable neoplasms, a better understanding of the clinicopathologic features is needed for the rare manifestations associated with treatment failure. We report a rare case of metastatic pure choriocarcinoma involving the small intestine arising from a testicular mixed germ cell tumor. In a patient who developed massive upper gastrointestinal hemorrhage during treatment, the intestinal metastases and focus of bleeding could only be determined by laparotomy. We propose an approach for the determination of subclinical intestinal metastases of testicular germ cell tumor; the case is discussed in light of similar reports in literature.