We investigated the vascular effects of glucagon-like peptide-1 (GLP-1) and Exendin-4 in type 2 diabetic rat aortae. Studies were performed in a normal control group (NC) (0.2 ml i.p. saline, n = 10), streptozotocin (STZ)/nicotinamide diabetic control group (DC) (a single dose of 80 mg/kg STZ i.p. injection 15 min after administration of 230 mg/kg nicotinamide i.p.), GLP-1 (GLPC) control group (1 µg/kg twice daily i.p. for 1 month, n = 10), Exendin-4 control group (EXC) (0.1 µg/kg twice daily i.p. for 1 month, n = 10), GLP-1-treated diabetic group (GLPT) (1 µg/kg twice daily i.p. for 1 month, n = 10), and Exendin-4-treated diabetic group (EXT) (0.1 µg/kg twice daily i.p. for 1 month, n = 10). One month of GLP-1 and Exendin-4 treatment significantly decreased the blood glucose levels of diabetic rats (113 ± 2 mg/dl, p < 0.001, and 117 ± 1 mg/dl, p < 0.001, respectively versus 181 ± 9 mg/dl in the DC group). Sensitivity (pD2) and maximum response (% Max. Relax) of acetylcholine-stimulated relaxations in the DC group (pD2: 6.73 ± 0.12 and 55 ± 6, respectively) were decreased compared with the non-diabetic NC group (pD2: 7.41 ± 0.25, p < 0.05, and 87 ± 4, p < 0.01). Treating diabetic rats with GLP-1, pD2 values and with Exendin-4, Max. Relax %values of aortic strips to acetylcholine returned to near non-diabetic NC values (pD2: 7.47 ± 0.15, p < 0.05, and 87 ± 3, p < 0.01, respectively). Maximal contractile responses (Emax) to noradrenaline in aortic strips from the diabetic DC group (341 ± 27 mg tension/mg wet weight) were significantly decreased compared with the non-diabetic NC (540 ± 66 mg tension/mg wet weight, p < 0.001) and the GLPT group (490 ± 25 mg tension/mg wet weight, p < 0.05). There were no significant differences in pD2 values of aortic strips to noradrenaline from all groups. Emax to KCl in aortic strips from the DC group (247 ± 10 mg tension/mg wet weight, p < 0.01) was significantly decreased compared with non-diabetic NC group (327 ± 26 mg tension/mg wet weight). Treating diabetic rats with GLP-1 (GLPT), Emax values of aortic strips to KCl returned to near non-diabetic NC values (271 ± 12 mg tension/mg wet weight). GLP-1 and (partially) Exendin-4 treatment could improve the increased blood glucose level and normalize the altered vascular tone in type 2 diabetic rats.
Many antibody and immune escape variants in SARS-CoV-2 are now documented in literature. The availability of SARS-CoV-2 genome sequences enabled us to investigate the occurrence and genetic epidemiology of the variants globally. Our analysis suggests that a number of genetic variants associated with immune escape have emerged in global populations.
Background: Structural and functional changes in potassium channels of vascular smooth muscle cells may contribute to the development of diseases such as hypertension. We aim to investigate the vascular effects of potassium channel openers and blockers in human internal mammary artery (HIMA). Methods: Remaining segments of HIMA from 18 consecutive patients undergoing coronary artery bypass surgery were obtained to examine the vascular effects of various potassium channel openers (staurosporine, hydrochlorothiazide and cromakalim) and potassium channel blockers (4-aminopyridin [4-AP], charybdotoxin [CTX] and glibenclamide [GLBC]). Results: Noradrenaline (NA)-induced maximal contractions were inhibited by all 3 K+-channel blockers but only fully inhibited by 4-AP (95.6%). Only NA-induced contractions were reversed by CTX. Only K+-induced maximal contractions were significantly inhibited by 4-AP (95.6%, p < 0.05). Only acetylcholine-induced relaxation was fully inhibited by CTX. Only sodium nitroprusside-induced relaxations in potassium chloride-precontracted strips could be reversed by GLBC. Conclusions: Drugs affecting potassium channels may be useful in the treatment of hypertension and management of perioperative vasospasm during the coronary artery bypass surgery.
BackgroundThere is a paucity of data on whether pre-operative walking and functional capacity has a direct association with post-operative gastrointestinal function in patients who have undergone surgery to treat gynecologic cancers.ObjectiveTo explore the relationship between pre-operative walking and post-operative recovery of bowel function.MethodsThis randomized trial was performed from January 1, 2018 to August 31, 2018. All patients had a diagnosis of endometrial or ovarian cancer and were scheduled for comprehensive staging. Group A served as the control group who did not walk regularly on the last night before surgery. Patients in group B walked for 30 min at an average speed of 3 km/h from 20.00 to 20.30 and 21.30. to 22.00 on the last night before surgery under the supervision of a nurse or doctor. The study was registered with clinicaltrials.gov (no: NCT03553121).ResultsA total of 85 patients were enrolled: 43 patients were assigned to the walking group and 42 to the control group. There were no significant differences in demographics between the groups. Median age was 57.3±8.5 in the control and 59.9±9.1 in the walking group. In addition, 28 patients had endometrial cancer and 14 had ovarian cancer in the control group. 33 patients and 10 patients in the walking group had endometrial and ovarian cancer, respectively. The mean time to first flatus was shorter in the walking group than in the control group (32.5±10.4 vs 40.6±16.9 hours, respectively; p=0.010). In addition, the time to first defecation was significantly shorter in the walking group (62.8±26.7 vs 91.4±51.8 hours; p=0.002). Patients who walked before surgery were less likely to have post-operative paralytic ileus (25.0% vs 60.7%; p=0.003). Walking before the operative period and laparoscopic surgery independently protected against the development of post-operative paralytic ileus.ConclusionWalking before surgery expedited time to bowel motility and ability to tolerate food. In addition, this method significantly decreased the risk of post-operative paralytic ileus.We consider that walking before surgery may be integrated into the pre-operative management of patients under going surgery for gynecologic cancers.Clinical trial registrationclinicaltrial.org record number: NCT03553121
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