The GLP-1 Receptor Agonist Liraglutide Increases Myocardial Glucose Oxidation Rates via Indirect Mechanisms and Mitigates Experimental Diabetic Cardiomyopathy

BackgroundType 2 diabetes (T2D) increases risk for cardiovascular disease. Of interest, liraglutide, a therapy for T2D that activates the glucagon-like peptide-1 receptor to augment insulin secretion, reduces cardiovascular-related death in people with T2D, though it remains unknown how liraglutide produces these actions. Notably, the glucagon-like peptide-1 receptor is not expressed in ventricular cardiac myocytes, making it likely that ventricular myocardium-independent actions are involved. We hypothesized that augmented insulin secretion may explain how liraglutide indirectly mediates cardioprotection, which thereby increases myocardial glucose oxidation.MethodsC57BL/6J male mice were fed either a low-fat diet (lean) or were subjected to experimental T2D and treated with either saline or liraglutide 3× over a 24-hour period. Mice were subsequently euthanized and had their hearts perfused in the working mode to assess energy metabolism. A separate cohort of mice with T2D were treated with either vehicle control or liraglutide for 2 weeks for the assessment of cardiac function via ultrasound echocardiography.ResultsTreatment of lean mice with liraglutide increased myocardial glucose oxidation without affecting glycolysis. Conversely, direct treatment of the isolated working heart with liraglutide had no effect on glucose oxidation. These findings were recapitulated in mice with T2D and associated with increased circulating insulin levels. Furthermore, liraglutide treatment alleviated diastolic dysfunction in mice with T2D, which was associated with enhanced pyruvate dehydrogenase activity, the rate-limiting enzyme of glucose oxidation.ConclusionsOur data demonstrate that liraglutide augments myocardial glucose oxidation via indirect mechanisms, which may contribute to how liraglutide improves cardiovascular outcomes in people with T2D.     

Fatal acute sodium phosphate enemas intoxication

We describe a patient who died as a result of severe hypocalcaemia and hyperphosphatemia after treatment with a sodium-phosphate enema. Physicians should be aware of the risk when using these enemas, even in normal doses, especially in elderly patients without signs of renal failure, as in our patient.     

Adverse effects related to thionamide drugs and their dose regimen

The authors studied 389 Graves' hyperthyroid patients receiving either high propylthiouracil (PTU) or methimazole (MMI) daily doses or low doses to evaluate whether adverse effects were related to the thionamide drugs or its daily dose regimen. Group 1 patients (n = 286) received high PTU (728 +/- 216 mg/day, n = 92) or MMI (60 +/- 19 mg/day, n = 94) doses, and group 2 patients (n = 103) were treated with low PTU (255 +/- 85 mg/day, n = 39) or MMI (23 +/- 10 mg/day, n = 64) doses. Major adverse effects were observed in 11 (2.8%) patients. Of these, four (1.0%) had agranulocytosis, two (0.5%) were granulocytopenic and five (1.3%) had hepatotoxicity. Agranulocytosis occurred in two patients from each group, 0.7% and 1.9%, respectively from group 1 and group 2. There was no significant difference between the groups or the types of thionamide. There also was no correlation with the patients' age. All of the patients were hyperthyroid, and its onset occurred in the first to third month of treatment. Full recovery was achieved in all cases after drug withdrawal. Four of 5 patients with hepatotoxicity were treated with high PTU doses, and one patient received low MMI doses (p less than .05). All patients were euthyroid. Arthralgias, skin rash and gastric intolerance, the minor adverse effects of thionamides studied, were observed in 52 (13.4%) of the patients. Although no significant differences were found, most of the patients experiencing side effects were from group 1 an received MMI therapy. These adverse effects did not demand drug withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)     

Barriers to physical activity during the COVID-19 pandemic in adults: a cross-sectional study

Sport Sciences for Health - Social isolation due to the coronavirus disease 2019 (COVID-19) pandemic has reduced physical activity levels in both men and women. The identification of barriers to...     

Recurrence After Transanal Excision of T1 Rectal Cancer: Should We Be Concerned?

PURPOSE Transanal excision is an appealing treatment for low rectal cancers because of its low morbidity, mortality, and better functional results than transabdominal procedures. However, controversy exists about whether it compromises the potential for cure. Several, recent reports of high recurrence rates after local excision prompted us to review our results of transanal excision alone in patients with T1 rectal cancers.METHODS All patients with T1 low rectal cancer undergoing local excision alone between 1980 through 1998 were reviewed for local recurrence, distant metastasis, disease-free interval, results of salvage surgery, and overall and disease-free survival. Demographics, tumor size, distance from anal verge, and preoperative endoluminal ultrasound results also were recorded. Patients with poorly differentiated tumors, perineural or lymphovascular invasion, or with mucinous component were excluded.RESULTS Fifty-two patients underwent transanal excision during the study period. Five-year recurrence was estimated to be 29.38 percent (95 percent confidence interval, 15.39–43.48). For 52 patients, five-year, cancer-specific and overall survival rates were 89 and 75 percent respectively. Fourteen of 15 patients with recurrence underwent salvage treatment with 56.2 percent (95 percent confidence interval, 35.2–90) five-year survival rate. Gender, preoperative staging by endorectal ultrasound, distance from the anal verge, tumor size, location, and T1 status discovered after transanal excision of a villous adenoma did not influence local recurrence or tumor-specific survival.CONCLUSIONS Transanal excision for T1 rectal tumors with low-grade malignancy has a high rate of recurrence. Although overall cancer survival rates might be regarded as satisfactory, this high recurrence and low salvage rate raises the issue about the role of transanal excision alone for early rectal cancer and the possible need for adjuvant therapy or increased role of resective surgery.Presented at the meeting of The American Society of Colon and Rectal Surgeons, Chicago, Illinois, June 3 to 7, 2002.     

A new variant of type II von Willebrand disease with aberrant multimeric structure of plasma but not platelet von Willebrand factor (type IIF)

A patient with a lifelong bleeding disorder was diagnosed as having Type II von Willebrand disease. The larger multimers of von Willebrand factor were absent from her plasma but present in platelets. A high- resolution electrophoretic technique was used to study the complex structure of individual von Willebrand factor multimers. In normal plasma, each multimer could be resolved into five bands: a more intense central one and four less intense, two moving faster and two slower than the central band. In normal platelets, each multimer could also be resolved into five bands. The central one had a mobility similar to that in plasma, whereas the four satellite bands had a mobility that differed from that of the corresponding plasma bands. In the patient, platelet von Willebrand factor antigen content and ristocetin cofactor activity were normal, and von Willebrand factor showed the same structure of individual multimers as seen in normal platelets. On the other hand, plasma von Willebrand factor antigen and ristocetin cofactor activity were decreased, and the structure of individual von Willebrand factor multimers was different from that of normal plasma and similar to that seen in normal and patient's platelets. After infusion of 1-deamino-8-D-arginine vasopressin, the largest von Willebrand factor multimers, as well as new satellite bands with a mobility similar to those in normal plasma, appeared in the patient plasma, and the levels of von Willebrand factor antigen and ristocetin cofactor activity became normal. Yet no relevant change in the prolonged bleeding time was observed. This new variant of von Willebrand disease, therefore, is characterized by the presence of a dysfunctional von Willebrand factor molecule that exhibits unique structural abnormalities in plasma but appears to be normal in platelets. The designation of Type IIF is proposed for this type of von Willebrand disease in accordance with the terminology that has been previously used.