Association of exercise training and angiotensin-converting enzyme 2 activator improves baroreflex sensitivity of spontaneously hypertensive rats.

The present study sought to determine cardiovascular effects of aerobic training associated with diminazene aceturate (DIZE), an activator of the angiotensin converting enzyme 2, in spontaneously hypertensive rats (SHRs). Male SHRs (280-350 g) were either subjected to exercise training or not (sedentary group). The trained group was subjected to 8 weeks of aerobic training on a treadmill (five times a week, lasting 60 min at an intensity of 50-60% of maximum aerobic speed). In the last 15 days of the experimental protocol, these groups were redistributed into four groups: i) sedentary SHRs with daily treatment of 1 mg/kg DIZE (S+D1); ii) trained SHRs with daily treatment of 1 mg/kg DIZE (T+D1); iii) sedentary SHRs with daily treatment of vehicle (S+V); and iv) trained SHRs with daily treatment of vehicle (T+V). After treatment, SHRs were anesthetized and subjected to artery and femoral vein cannulation prior to the implantation of ECG electrode. After 24 h, mean arterial pressure (MAP) and heart rate (HR) were recorded; the baroreflex sensitivity and the effect of double autonomic blockade (DAB) were evaluated in non-anesthetized SHRs. DIZE treatment improved baroreflex sensitivity in the T+D1 group as compared with the T+V and S+D1 groups. The intrinsic heart rate (IHR) and MAP were reduced in T+D1 group as compared with T+V and S+D1 groups. Hence, we conclude that the association of exercise training with DIZE treatment improved baroreflex function and cardiovascular regulation.

Association of exercise training and angiotensin-converting enzyme 2 activator improves baroreflex sensitivity of spontaneously hypertensive rats

The present study sought to determine cardiovascular effects of aerobic training associated with diminazene aceturate (DIZE), an activator of the angiotensin converting enzyme 2, in spontaneously hypertensive rats (SHRs). Male SHRs (280–350 g) were either subjected to exercise training or not (sedentary group). The trained group was subjected to 8 weeks of aerobic training on a treadmill (five times a week, lasting 60 min at an intensity of 50–60% of maximum aerobic speed). In the last 15 days of the experimental protocol, these groups were redistributed into four groups: i) sedentary SHRs with daily treatment of 1 mg/kg DIZE (S+D1); ii) trained SHRs with daily treatment of 1 mg/kg DIZE (T+D1); iii) sedentary SHRs with daily treatment of vehicle (S+V); and iv) trained SHRs with daily treatment of vehicle (T+V). After treatment, SHRs were anesthetized and subjected to artery and femoral vein cannulation prior to the implantation of ECG electrode. After 24 h, mean arterial pressure (MAP) and heart rate (HR) were recorded; the baroreflex sensitivity and the effect of double autonomic blockade (DAB) were evaluated in non-anesthetized SHRs. DIZE treatment improved baroreflex sensitivity in the T+D1 group as compared with the T+V and S+D1 groups. The intrinsic heart rate (IHR) and MAP were reduced in T+D1 group as compared with T+V and S+D1 groups. Hence, we conclude that the association of exercise training with DIZE treatment improved baroreflex function and cardiovascular regulation.

Involvement of CYP1A1, GST, 72TP53 polymorphisms in the pathogenesis of thyroid nodules.

Specific genotypes appear to be related to the development of thyroid disease. We examined whether polymorphisms of the genes CYP1A1, GSTM1, GSTT1, and TP53 at codon 72 are associated with increased risk for thyroid nodules. Blood samples were obtained from 122 thyroid patients with nodules and from 134 healthy control individuals from Goiânia city, GO, Brazil. We found no significant association of CYP1A1m1 and CYP1A1m2 genotypes with thyroid diseases (P > 0.05). The null genotypes of GSTM1 and GSTT1 genes were predominant in patients with nodules, indicating that individuals that possess these genotypes have a predisposition for thyroid disease. The genotype p53Arg Arg was associated with a low risk for thyroid cancer (OR = 0.15; P < 0.0001), indicating that the arginine allele in homozygosis could have a protective effect against carcinogenesis. On the other hand, the p53ArgPro genotype was significantly associated with malignant neoplastic nodules (OR = 3.65; P = 0.001). Interindividual variation in susceptibility to thyroid diseases could provide new perspectives for early diagnosis, prognosis and treatment, indicating which patients with thyroid nodules will benefit from treatment, depending on specific polymorphic profiles.

TP53 codon 72 polymorphism in adult soft tissue sarcomas.

Soft tissue sarcomas (STS) are tumors of mesodermal origin, comprising about 1% of all adult neoplasms. Management of such tumors is an important medical challenge. TP53 codon 72 polymorphism results in either the arginine or proline form of the p53 protein; several studies have investigated whether codon 72 polymorphisms are risk and prognostic factors for cancer. We investigated p53 codon 72 polymorphism (Arg72Pro) frequencies with respect to the susceptibility and the clinical outcome of patients with STS. A series of 100 STS were genotyped for the p53 Arg72Pro polymorphism using polymerase chain reaction. Genotype frequencies were compared to a group of 85 healthy donors (controls). Possible associations between polymorphic genotypes, clinicopathological factors and survival of STS patients were also investigated. Genotypic frequencies obtained for STS patients did not significantly differ from that obtained for controls. In the STS group, p53 codon 72 polymorphic variants were not significantly associated with gender, age, tumor size, clinical stage, tumor grade, histology, or nodal or distant metastasis. The five-year overall survival rate for the STS group was 48%; it was significantly affected by tumor grade, clinical stage, and nodal and distant metastasis. Soft tissue sarcoma patients with the Pro/Pro variant had a reduced survival rate (30%), when compared to the p53 Arg/Arg (45%) and the p53 Arg/Pro groups (55%). However, the differences between these groups were not significant (P = 0.44).