One unknown impurity(Imp-II)during the analysis of laboratory batches of isoproterenol hydrochloride was detected in the level ranging from 0.04% to 0.12% by high performance liquid chromatography with UV detection. The unknown impurity structure was proposed as 4-[2-(propan-2-ylamino)ethyl]benzene-1,2-diol (Imp-Ⅱ)using the liquid chromatography–mass spectrophotometry(LC–MS)analysis.Imp-Ⅱ was isolated by semi-preparative liquid chromatography from the impurity-enriched reaction crude sample. Its proposed structure was confirmed by nuclear magnetic spectroscopy such as 1H, 13C,DEPT(1D NMR),HSQC(2D NMR) and infrared spectroscopy(IR),and retention time and purity with HPLC followed by the chemical synthesis. Due to less removable nature of Imp-II during the purification,the synthetic process was optimized proficiently to control the formation of Imp-II below to the limit<0.12% in the course of reaction.The new chemical route was developed for the preparation of this impurity in required quantity with purity to use as reference standard. The most probable mechanism for the formation of Imp-II was discussed in details.

Background: Status epilepticus, when continued despite the administration of two antiepileptic drugs, is called refractory status epilepticus (RSE). The seizure-like phenomenon due to propofol is widely reported in the literature. However, RSE caused by propofol is rare and is a diagnostic dilemma. Case: A 44-year-old male patient presented with RSE during the intraoperative period and was under general anesthesia on propofol infusion. The seizure was resistant to benzodiazepines and phenytoin. Thereafter, the seizure subsided after the discontinuation of propofol infusion, and the patient was shifted to fentanyl and dexmedetomidine infusion for the maintenance of anesthesia. The postoperative follow-up was uneventful. Conclusions This article focuses on the management of intractable intraoperative seizure and highlights the need for the exploration of seizure characteristics caused by propofol.

OBJECTIVETo evaluate the analgesic, anti-inflammatory and antipyretic activity of methanolic Tecomaria capensis (T. capensis) leaves extract using different models in rats.

METHODSMethanolic T. capensis leaves extract (100, 300, 1000 and 2000 mg/kg body weight) was given to rats orally to observe acute toxicity, and observed for 14 days. Analgesic activity was evaluated using tail immersion and formalin induced paw licking models in rats. Anti-inflammatory activity was evaluated using carrageenan induced paw edema model in rats. Antipyretic activity was evaluated using brewer's yeast induced pyrexia model in rats. Methanolic T. capensis leaves extract were given at dose of 100, 200 and 500 mg/kg p.o.

RESULTSResults demonstrated that the no mortality was reported even after 14 days. This indicated that the methanol extract was safe up to a single dose of 2 000 mg/kg body weight. Methanolic T. capensis leaves extract (100, 200 and 500 mg/kg p.o.) significantly increased the latency period in the tail immersion test, reduced the licking time in both the neurogenic and inflammatory phases in the formalin test. Methanolic T. capensis leaves extract (100, 200 and 500 mg/kg p.o.) significantly prevented increase in volume of paw edema. Methanolic T. capensis leaves extract at the doses of (100, 200 and 500 mg/kg p.o.) significantly decreased the rectal temperature of the rats.

CONCLUSIONSThis study exhibites that methanolic T. capensis leaves extract possesses analgesic, anti-inflammatory and antipyretic activity which may be mediated by the central and peripheral mechanisms.

Analgesics ; chemistry ; pharmacology ; therapeutic use ; toxicity ; Animals ; Anti-Inflammatory Agents ; chemistry ; pharmacology ; therapeutic use ; toxicity ; Antipyretics ; chemistry ; pharmacology ; therapeutic use ; toxicity ; Behavior, Animal ; drug effects ; Bignoniaceae ; chemistry ; Disease Models, Animal ; Edema ; Female ; Fever ; Male ; Pain Management ; methods ; Pain Measurement ; Plant Extracts ; chemistry ; pharmacology ; therapeutic use ; toxicity ; Plant Leaves ; chemistry ; Rats

Itolizumab downregulates the synthesis of proinflammatory cytokines and adhesion molecules by inhibiting CD6 leading to lower levels of interferon-γ, interleukin-6, and tumor necrotic factor-α and reduced T-cell infiltration at inflammatory sites. This study aims to compare the effects of tocilizumab and itolizumab in the management of severe coronavirus disease 2019 (COVID-19). Methods: The study population was adults (>18 years) with severe COVID-19 pneumonia admitted to the intensive care unit receiving either tocilizumab or itolizumab during their stay. The primary outcome was clinical improvement (CI), defined as a two-point reduction on a seven-point ordinal scale in the status of the patient from initiating the drug or live discharge. The secondary outcomes were time until CI, improvement in PO2 /FiO2 ratio, best PO2 /FiO2 ratio, need for mechanical ventilation after administration of study drugs, time to discharge, and survival days. Results: Of the 126 patients included in the study, 92 received tocilizumab and 34 received itolizumab. CI was seen in 46.7% and 61.7% of the patients in the tocilizumab and itolizumab groups, respectively and was not statistically significant (P=0.134). The PO2 /FiO2 ratio was significantly better with itolizumab compared to tocilizumab (median [interquartile range]: 315 [200–380] vs. 250 [150–350], P=0.043). The incidence of serious adverse events due to the study drugs was significantly higher with itolizumab compared to tocilizumab (14.7% vs. 3.3%, P=0.032). Conclusions: The CI with itolizumab is similar to tocilizumab. Better oxygenation can be achieved with itolizumab and it can be a substitute for tocilizumab in managing severe COVID-19.

Itolizumab downregulates the synthesis of proinflammatory cytokines and adhesion molecules by inhibiting CD6 leading to lower levels of interferon-γ, interleukin-6, and tumor necrotic factor-α and reduced T-cell infiltration at inflammatory sites. This study aims to compare the effects of tocilizumab and itolizumab in the management of severe coronavirus disease 2019 (COVID-19). Methods: The study population was adults (>18 years) with severe COVID-19 pneumonia admitted to the intensive care unit receiving either tocilizumab or itolizumab during their stay. The primary outcome was clinical improvement (CI), defined as a two-point reduction on a seven-point ordinal scale in the status of the patient from initiating the drug or live discharge. The secondary outcomes were time until CI, improvement in PO2 /FiO2 ratio, best PO2 /FiO2 ratio, need for mechanical ventilation after administration of study drugs, time to discharge, and survival days. Results: Of the 126 patients included in the study, 92 received tocilizumab and 34 received itolizumab. CI was seen in 46.7% and 61.7% of the patients in the tocilizumab and itolizumab groups, respectively and was not statistically significant (P=0.134). The PO2 /FiO2 ratio was significantly better with itolizumab compared to tocilizumab (median [interquartile range]: 315 [200–380] vs. 250 [150–350], P=0.043). The incidence of serious adverse events due to the study drugs was significantly higher with itolizumab compared to tocilizumab (14.7% vs. 3.3%, P=0.032). Conclusions: The CI with itolizumab is similar to tocilizumab. Better oxygenation can be achieved with itolizumab and it can be a substitute for tocilizumab in managing severe COVID-19.

Itolizumab downregulates the synthesis of proinflammatory cytokines and adhesion molecules by inhibiting CD6 leading to lower levels of interferon-γ, interleukin-6, and tumor necrotic factor-α and reduced T-cell infiltration at inflammatory sites. This study aims to compare the effects of tocilizumab and itolizumab in the management of severe coronavirus disease 2019 (COVID-19). Methods: The study population was adults (>18 years) with severe COVID-19 pneumonia admitted to the intensive care unit receiving either tocilizumab or itolizumab during their stay. The primary outcome was clinical improvement (CI), defined as a two-point reduction on a seven-point ordinal scale in the status of the patient from initiating the drug or live discharge. The secondary outcomes were time until CI, improvement in PO2 /FiO2 ratio, best PO2 /FiO2 ratio, need for mechanical ventilation after administration of study drugs, time to discharge, and survival days. Results: Of the 126 patients included in the study, 92 received tocilizumab and 34 received itolizumab. CI was seen in 46.7% and 61.7% of the patients in the tocilizumab and itolizumab groups, respectively and was not statistically significant (P=0.134). The PO2 /FiO2 ratio was significantly better with itolizumab compared to tocilizumab (median [interquartile range]: 315 [200–380] vs. 250 [150–350], P=0.043). The incidence of serious adverse events due to the study drugs was significantly higher with itolizumab compared to tocilizumab (14.7% vs. 3.3%, P=0.032). Conclusions: The CI with itolizumab is similar to tocilizumab. Better oxygenation can be achieved with itolizumab and it can be a substitute for tocilizumab in managing severe COVID-19.

Itolizumab downregulates the synthesis of proinflammatory cytokines and adhesion molecules by inhibiting CD6 leading to lower levels of interferon-γ, interleukin-6, and tumor necrotic factor-α and reduced T-cell infiltration at inflammatory sites. This study aims to compare the effects of tocilizumab and itolizumab in the management of severe coronavirus disease 2019 (COVID-19). Methods: The study population was adults (>18 years) with severe COVID-19 pneumonia admitted to the intensive care unit receiving either tocilizumab or itolizumab during their stay. The primary outcome was clinical improvement (CI), defined as a two-point reduction on a seven-point ordinal scale in the status of the patient from initiating the drug or live discharge. The secondary outcomes were time until CI, improvement in PO2 /FiO2 ratio, best PO2 /FiO2 ratio, need for mechanical ventilation after administration of study drugs, time to discharge, and survival days. Results: Of the 126 patients included in the study, 92 received tocilizumab and 34 received itolizumab. CI was seen in 46.7% and 61.7% of the patients in the tocilizumab and itolizumab groups, respectively and was not statistically significant (P=0.134). The PO2 /FiO2 ratio was significantly better with itolizumab compared to tocilizumab (median [interquartile range]: 315 [200–380] vs. 250 [150–350], P=0.043). The incidence of serious adverse events due to the study drugs was significantly higher with itolizumab compared to tocilizumab (14.7% vs. 3.3%, P=0.032). Conclusions: The CI with itolizumab is similar to tocilizumab. Better oxygenation can be achieved with itolizumab and it can be a substitute for tocilizumab in managing severe COVID-19.

STUDY DESIGN: Single-surgeon, single-center prospective study with prospective data collection. PURPOSE: To clinically evaluate muscle damage after open lumbar surgery and its relationship to functional activity and to validatethe improvement in function as indicated by improved Oswestry Disability Index (ODI) score despite muscle damage. OVERVIEW OF LITERATURE: Few studies have analyzed the functional loss and recovery pattern of muscles after open lumbar surgery. METHODS: The study included 30 patients who underwent open lumbar spine fusion surgery at our institution between August 2013 and May 2015. Preoperatively and at 6 months postoperatively, the patients were subjected to functional, biochemical, electrophysiological, and radiological assessments as outpatients, and the results were compared. RESULTS: Mean preoperative and 6-month postoperative values were as follows: creatine phosphokinase levels, 133.07±17.57 and 139±17.7 U/L (p<0.001); Visual Analog Scale scores for backache, 6.73±0.88 and 3.27±0.96 (p<0.001); and ODI scores, 41.6±5.51 and 22.4±4.48 (p<0.001), respectively. Preoperatively, electrophysiological studies showed that 20% of the patients had a polyphasic configuration whereas at 6 months postoperatively, all patients had polyphasic configuration (p<0.001). The mean cross-sectional area of the multifidus observed using magnetic resonance imaging (MRI) decreased from 742.67±76.62 mm2 preoperatively to 598.27±66.38 mm2 6 months postoperatively (p<0.001), with all the patients exhibiting grade 2 atrophy. CONCLUSIONS: Open lumbar fusion surgery resulted in significant damage to the lumbar paraspinal muscles, as indicated by a reduction in the cross-sectional area of the multifidus by MRI and denervation of the multifidus demonstrated using electromyography. Nevertheless, the patients reported reduced back pain and improved quality of life, which may have been due to increased stability of the previously unstable lumbar spinal segment after the surgery.
Atrophy ; Back Pain ; Creatine Kinase ; Data Collection ; Denervation ; Electromyography ; Humans ; Magnetic Resonance Imaging ; Muscles ; Outpatients ; Paraspinal Muscles ; Prospective Studies ; Quality of Life ; Spine ; Visual Analog Scale

Background: Opioids administered as bolus doses or continuous infusions are widely used by anesthesiologists worldwide for major and day care surgeries. Opioid-free anesthesia is a multimodal anesthesia and analgesia technique that does not use opioid drugs, thereby benefitting patients from opioid-related adverse effects. In this study, we compared the postoperative analgesic requirements of patients scheduled for elective laparoscopic cholecystectomy under opioid-free and opioid-based anesthesia. Methods: This study included 88 patients aged 18–60 years with American Society of Anesthesiologists physical status 1 and 2 who underwent elective laparoscopic cholecystectomy. Participants were randomly divided into two groups with forty-four participants in each group. The opioid-free anesthesia group was administered an intravenous bolus of ketamine and dexmedetomidine, whereas the opioid-based group was administered fentanyl with conventional general anesthesia. The primary outcome was to compare the total amount of fentanyl consumed by both groups during the 6 h postoperative period following extubation. Episodes of postoperative nausea and vomiting (PONV) and vital signs were noted throughout the postoperative period to analyze the secondary outcomes. Results: Both the groups had similar demographic characteristics. The opioid-free group required less postoperative analgesia within the first 2 h (61.4 ± 17.4 vs. 79.0 ± 19.4 of fentanyl, P < 0.001), which was statistically significant. However, fentanyl consumption was comparable between the groups at the sixth postoperative hour (opioid-free group 152 ± 28.2 vs. opioid group 164 ± 33.4, P = 0.061). Compared with 4.5% of the participants in the opioid-free group, 34% of those in the opioid-based group developed moderate PONV. Conclusions The opioid-free anesthesia technique in patients undergoing laparoscopic cholecystectomy reduced the requirement of analgesia in the first two hours of the postoperative period and was associated with decreased PONV.

Quantitative trait loci (QTL) analysis was conducted in bread wheat for 14 important traits utilizing data from four different mapping populations involving different approaches of QTL analysis. Analysis for grain protein content (GPC) suggested that the major part of genetic variation for this trait is due to environmental interactions. In contrast, pre-harvest sprouting tolerance (PHST) was controlled mainly by main effect QTL (M-QTL) with very little genetic variation due to environmental interactions; a major QTL for PHST was detected on chromosome arm 3AL. For grain weight, one QTL each was detected on chromosome arms 1AS, 2BS and 7AS. QTL for 4 growth related traits taken together detected by different methods ranged from 37 to 40; nine QTL that were detected by single-locus as well as two-locus analyses were all M-QTL. Similarly, single-locus and two-locus QTL analyses for seven yield and yield contributing traits in two populations respectively allowed detection of 25 and 50 QTL by composite interval mapping (CIM), 16 and 25 QTL by multiple-trait composite interval mapping (MCIM) and 38 and 37 QTL by two-locus analyses. These studies should prove useful in QTL cloning and wheat improvement through marker aided selection.
Bread ; Chromosome Mapping ; Quantitative Trait Loci ; genetics ; Triticum ; genetics ; growth & development