Angiotensin-converting enzyme 2 as a potential therapeutic target for COVID-19:A review / 药物分析学报

As of August 16,2021,there have been 207,173,086 confirmed cases and 4,361,996 deaths due to the coronavirus disease(COVID-19),and the pandemic remains a global challenge.To date,no effective and approved drugs are available for the treatment of COVID-19.Angiotensin-converting enzyme 2(ACE2)plays a crucial role in the invasion into host cells by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the etiological agent of COVID-19.Notably,ACE2 density is influenced by medical con-ditions,such as hypertension,or by drugs,including angiotensin-converting enzyme inhibitors(ACEIs)and angiotensin receptor blockers(ARBs),which can change the fate of SARS-CoV-2 infectivity.ACE2 is a target for these drugs and can be manipulated to limit the viral entry and replication within the cells.Different strategies aimed at blocking ACE2 with small molecules,peptides,and antibodies,or by neutralizing the virus through its competitive binding with human recombinant soluble ACE2(hrsACE2)are currently under investigation.In this article,we review the current state of knowledge that em-phasizes the need to find effective therapeutic agents against COVID-19 by exploiting ACE2 as a potential target.The increased soluble ACE2 levels and the application of hrsACE2 in patients with COVID-19 can be implemented to control the disease.It has not yet been established whether hypertension and other comorbidities,independent of age,have a direct role in COVID-19.Therefore,the use of renin-angiotensin system inhibitors,ACEls and ARBs,should not be discontinued during COVID-19 treatment.

Epidural bupivacaine combined with dexmedetomidine or clonidine in infraumbilical surgeries: a comparative evaluation.

Background: Alpha-2 agonist are being extensively evaluated as an alternative to neuraxial opoids, as an adjuvants in regional anaesthesia The faster onset of action of local anaesthetics, rapid establishment of both sensory and motor blockade, prolonged duration of analgesia into postoperative period, dose sparing action of local anaesthetics and stable cardiovascular parameters make these agents a very effective adjuvant in regional anaesthesia. Methods: Our study had 45 patients, all patients belonged to ASA Grade-I or II, between 20 and 55 years of age with an average height of 150 and 170 cm and have ideal body weight requiring neuraxial blockade for lower abdominal surgeries. All the patients were randomly allocated into two groups Group-I: Epidural bupivacaine 0.5% (16 ml) + clonidine 75 μgm (1 ml) Group-II: Epidural bupivacaine 0.5 % (16 ml) + Dexmedetomidine 50 μgm (1 ml) Patients were monitored for sensory and motor blockade, hemodynamic parameters, rescue analgesia, sedation and adverse effects in perioperative period. Results: The time of onset of sensory block at T10 and time to reach maximum sensory block (T6) in group-I was significantly longer as compared to group-II. The complete motor blockade (grade-3) was achieved much later and time taken for recovery to grade-0 was significantly shorter in group-I. The time for rescue analgesia in group-I was significantly shorter as compared to group-II. Hypotension was the most common side effect in both the groups. Dry mouth is a known side effect of alpha-2 agonists. Epidural dexmedetomidine produced profound sedation. Conclusions: We conclude from this study that dexmedetomidine is a better adjuvant than clonidine for providing early onset of sensory analgesia, superior sedative properties and prolonged post-operative analgesia.

Epidural ropivacaine combined with fentanyl or in combination with clonidine in infraumblical surgeries: a comparative study.

Background: The addition of an adjuvant, like clonidine and fentanyl, in epidural blockade has enhanced the effectiveness of local anaesthetics as they not only help in intensifying and prolonging the blockade effect but also help in the reduction of the dose of local anaesthetics. Methods: Our study had 45 patients, all patients belonged to ASA grade-I or II, between 20 and 55 years of age requiring neuraxial blockade for lower abdominal surgeries. All the patients were randomly allocated into two groups. Group-I: Epidural ropivacaine 0.75% (14.5ml) + Fentanyl 50 μgm (1 ml) + 0.5 ml distilled water. Group-II: Epidural ropivacaine 0.75% (14.5ml) + Fentanyl 50 μgm (1 ml) + clonidine 50 μgm. Patients were monitored for sensory and motor blockade, hemodynamic parameters, rescue analgesia and adverse effects in perioperative period. Results: Highest level of sensory and motor blockade was found to be insignificant (p>0.05) in both the groups. Mean time for regression of sensory blockade to T10 was significantly longer (p<0.05) in group II as compared to group I. The duration of motor blockade was significantly (p<0.001) higher in patients of Group-II as compared to Group-I. The addition of clonidine to epidural Ropivacaine and fentanyl (Group-II) produces longer duration of analgesia as compared to Group-I. Haemodynamically the patients in both the groups behaved similarly. The patients, in whom epidural fentanyl was used, had slightly higher incidence of nausea, vomiting, dry mouth and pruritus. Conclusions: So this study re-established the fact, that the fentanyl and clonidine when added as adjuvant to epidural ropivacaine, significantly prolongs the analgesic duration without causing significant hemodynamic and respiratory changes.

Prediction of morbidity and mortality in middle and old aged surgical patients-comparison of standard scoring system and addition of echocardiography with hemodynamic indices.

Background: A prospective study was carried out in our hospital to predict morbidity and mortality in middle and old aged surgical patients by adding echocardiography to standard scoring system with hemodynamic studies. Methods: A total of 50 patients of either sex ranging from 40-70 years of ASA grade 1 & 2 scheduled for various types of noncardiac surgeries were enrolled for the study in our hospital. Patients were divided in two groups according to echocardiographic examinations. The patients with normal echocardiographic values were kept in control group and the patients with abnormal values were kept under study group. The patients in study group were further divided in three groups according to LVEF. Group1-LEVF≥60%, Group2-LVEF≥50-59%, Gr3≥40-49% Tab lorazepam was given to all the patients’ orally prior night of surgery. All the patients were induced with same type inducing agents according to body weight. All the patients were maintained on IPPV by anaesthesia machine with supplemental fentanyl, N2O, O2 and muscle relaxant. SPO2, electrocardiograph (ECG), Non-invasive/invasive blood pressure (BP), Spirometry, Capnography and temperature were monitored. At the end of the research project data’s were compiled systematically and were subjected to statistical analysis using odd’s ratio(OR),95% confidence interval (CI), z value and p value, two statistical software programme were used. Results: Significant difference in the results seen between the three study groups (Gr1, Gr2, Gr3) for perioperative ischemic changes, CHF and arrhythmias. Conclusions: In conclusion preoperative TTE before non-cardiac surgery can predict the risk of perioperative cardiac complications in known or suspected cases of cardiac disease patients.

Expression of mRNAs encoding tumor necrosis factor-alpha and its receptor-I in buffalo ovary.

The tumor necrosis factor-alpha (TNF-alpha) plays an important role in ovarian follicular development and ovulation process and acts through its receptor (TNFRI). The present investigation describes the expression of mRNAs encoding TNF-alpha and TNFRI in relation to glyceraldehyde-3-phosphate dehydrogenase (G3PDH) and beta-actin as control genes, using RT-PCR, in granulosa cells, intact follicles and luteal tissues from buffalo ovary. There was significant higher expression of mRNAs encoding TNF-alpha in granulosa cells from medium follicles and TNFRI expression increased with increase in size of follicles. Post-ovulatory structures (corpus luteum and corpus albicans) exhibited significantly higher expression of TNFRI mRNAs as compared to that obtained in intact follicles suggesting its immediate and critical role just after ovulation, for mediating TNF-alpha action on these tissues. Though the expression of TNF-alpha mRNA was stimulated by treatment of granulosa cells with FSH during culture, the expression of TNFRI mRNA did not change. The FSH alongwith IGF-I did not exert any effect. These results suggested an important role of TNF-alpha and its receptor in buffalo ovarian functions.

DNA isolation from goat blood using different brands of household detergents and its downstream application.

Rapid isolation of DNA from goat blood using different brands of detergents available in Indian market, is reported. The integrity and efficiency of these DNA preparations were compared with genomic DNA isolated by a standard kit (Flexi gene DNA kit), using amplification of exon 2 of CYP19 (aromatase) gene. The similar and significant amplification of this gene was obtained using genomic DNA isolated by kit and various detergents. However, among the detergents used, the Rin and Ezee were found to be the best to get DNA of high purity comparable to that obtained by kit.