In-vitro and in-silico investigations of SLC-0111 hydrazinyl analogs as human carbonic anhydrase I, II, IX, and XII inhibitors.

Two novel series of hydrazinyl-based benzenesulfonamides 9a-j and 10a-j were designed and synthesized using SLC-0111 as the lead molecule. The newly synthesized compounds were evaluated for their inhibitory activity against four different human carbonic anhydrase (hCA) isoforms I, II, IX, and XII. Both the series reported here were practically inactive against the off-target isozyme hCA I. Notably, derivative 10a exhibited superior potency (Ki of 10.2 nM) than acetazolamide (AAZ) against the cytosolic isoform hCA II. The hCA IX and XII isoforms implicated in tumor progression were effectively inhibited with Kis in the low nanomolar range of 20.5-176.6 nM and 6.0-127.5 nM, respectively. Compound 9g emerged as the most potent and selective hCA IX and XII inhibitor with Ki of 20.5 nM and SI of 200.1, and Ki of 6.0 nM and SI of 683.7, respectively, over hCA I. Furthermore, six compounds (9a, 9h, 10a, 10g, 10i, and 10j) exhibited significant inhibition toward hCA IX (Kis = 27.0, 41.1, 27.4, 25.9, 40.7, and 30.8 nM) relative to AAZ and SLC-0111 (Kis = 25.0 and 45.0 nM, respectively). These findings underscore the potential of these derivatives as potent and selective inhibitors of hCA IX and XII over the off-target hCA I and II.

Novel 1,2,4-triazoles as selective carbonic anhydrase inhibitors showing ancillary anticathepsin B activity.

Background: Exploration of the multi-target approach considering both human carbonic anhydrase (hCA) IX and XII and cathepsin B is a promising strategy to target cancer. Methodology & Results: 22 novel 1,2,4-triazole derivatives were synthesized and evaluated for their inhibition efficacy against hCA I, II, IX, XII isoforms and cathepsin B. The compounds demonstrated effective inhibition against hCA IX and/or XII isoforms with considerable selectivity over off-target hCA I/II. All compounds presented significant anticathepsin B activities at a low concentration of 10-7 M and in vitro results were also supported by the molecular modeling studies. Conclusion: Insights of present study can be utilized in the rational design of effective and selective hCA IX and XII inhibitors capable of inhibiting cathepsin B.

Fabricated Metal-Organic Frameworks (MOFs) as luminescent and electrochemical biosensors for cancer biomarkers detection.

In the health domain, a major challenge is the detection of diseases using rapid and cost-effective techniques. Most of the existing cancer detection methods show poor sensitivity and selectivity and are time consuming with high cost. To overcome this challenge, we analyzed porous fabricated metal-organic frameworks (MOFs) that have better structures and porosities for enhanced biomarker sensing. Here, we summarize the use of fabricated MOF luminescence and electrochemical sensors in devices for cancer biomarker detection. Various strategies of fabrication and the role of fabricated materials in sensing cancer biomarkers have been studied and described. The structural properties, sensing mechanisms, roles of noncovalent interactions, limits of detection, modeling, advantages, and limitations of MOF sensors have been well-discussed. The study presents an innovative technique to detect the cancer biomarkers by the use of luminescence and electrochemical MOF sensors. In addition, the potential association studies have been opening the way for personalized patient treatments and the development of new cancer-detecting devices.

Anesthesiologist's Role in Relieving Patient's Anxiety.

INTRODUCTION: Anesthesia and surgery have proved to be highly anxiety provoking and with the rise of elective surgery, its aspect of patient's experience has become prominent in time. However, our fault as anesthesiologists is that we have not made people get versed with what we people as anesthesiologist do in the operating room. Hence, keeping in view all this, a study was carried out, in which video information/images regarding anesthesia and surgical procedure was shown to patients on PowerPoint Presentation. Different images showing previous patient's hospital journey were shown to educate patients. METHODS: Two hundred patients scheduled to undergo elective surgery were taken and were divided into two groups of 100 each. Patients (study group or Group I) were shown video clippings/images of other previously operated patients and their hospital journey including surgery and anesthesia for which patient came in hospital. The study was carried out on the patient in each group while Group II was treated in normal way and not shown any type of images/videos. Hamilton Anxiety Rating Scale was used as a criterion to measure the level of anxiety in Group I and II at four different intervals that are before pre anesthetic check up (PAC), after showing videos and images in Group I, 1 h before surgery and 8 h after surgery. STATISTICAL ANALYSIS: The results of observation of both the groups at different intervals time were statistically compared and analyzed. These characteristics were analyzed using the "Chi-square tests" and "unpaired t-test." RESULTS: Video and images information if done preoperatively have been shown to reduce patient's anxiety, although little is known regarding the effects of the method. CONCLUSION: Showing videos/images of hospital journey for educating the patients before the operation is beneficial to patients undergoing elective surgery.

Efficacy and safety of propofol versus midazolam in fiberoptic endotracheal intubation.

BACKGROUND: Fiberoptic intubation is a technique commonly used for difficult airways. Conscious sedation is desirable to make this procedure tolerable, and it is essential that patients are cooperative, relaxed, and comfortable especially when difficult airway anatomy or pathology is encountered. OBJECTIVE: To compare the safety and efficacy of propofol versus midazolam in oral fiberoptic endotracheal intubation in terms of hemodynamic changes, level of sedation, ease of intubation, and patient comfort and complications. MATERIALS AND METHODS: In a prospective randomized study, 60 patients of age group 18-60 years and American Society of Anesthesiologists health classification of I and II with anticipated difficult intubation were randomly allocated into two groups. Both the groups were premedicated with injection glycopyrrolate 0.005 mg/kg and injection butorphanol 1 mg and nebulized with 4 ml of 4% lignocaine starting 20 min before the surgery. After that patients in Group I received intravenous propofol 1-2 mg/kg to a maximum of 2 mg/kg followed by 20 mg increments if needed and Group II received 0.05 mg/kg midazolam followed by 2 mg increments till the adequate level of sedation was reached. Patients were monitored for hemodynamic parameters, sedation according to observer's assessment of alertness score, intubation score, intubation time, patient comfort, satisfaction score, and complications, if any. Results were statistically analyzed. RESULTS: The mean sedation score, patient comfort score, and patient satisfaction were greater in propofol group (P < 0.05) but there were no significant differences in hemodynamics, intubating conditions, and complications. CONCLUSION: We conclude that compared with midazolam, propofol provides better sedation for fiberoptic endotracheal intubation and better patient comfort and satisfaction.

Anesthesiologist: The silent force behind the scene.

The Anesthesiologist provides continuous medical care before, during, and after operation to permit the surgeons to perform surgeries; sometimes quite challenging that could otherwise cause substantial threats to the patient's survival. Anesthesiologists, because of their combination of skills are uniquely qualified to care for dying patients suffering from end diseases like cancer. These skills include knowledge of analgesic and sedative pharmacology for the management of pain, awareness of perceptual alterations along with well-known skills in drug titration and experience with critically ill and highly anxious, often agitated patients under stressful circumstances. Anesthesiologists are physicians who provide medical care to patients in a wide variety of situations. This includes preoperative evaluation, consultation with the surgical team, creation of a plan for the anesthesia (which is different in each patient), airway management, intraoperative life support, pain control, intraoperative stabilization of all the vitals, postoperative pain management. Outside the operating room, Anesthesiologist's spectrum of action includes with general emergencies, trauma, intensive care units, acute and chronic pain management. In spite of providing these highly skilled services, Anesthesiologists are facing a lot of stress these days which predisposes them to burnout, fatigue, substance abuse, and suicide. The practice of anesthesia in Indian scenario is different as compared to the western countries. In India, the Anesthesiologists are dependent on surgeons for their work. The degree of stress faced is due to a number of factors like the type and quality of work, his/her relationship with surgeons and the support he/she receives from colleagues and family.