[Increased vascular density with indirect myocardial revascularization in normal rat hearts]. / Mayor densidad vascular con revascularización miocárdica indirecta en corazones normales de ratas

BACKGROUND: The aim of this study was to identify if the interaction of myocardial revascularization methods increases the functional vascular area. METHODS: A 4x3 factorial design was performed in 11 groups, five rats per group, ten samples per rat, evaluated at 45 days postoperative, with different surgical combinations. The magnitude of the interaction was evaluated by immunoexpression of vascular endothelium-derived growth factor, fibroblast growth factor and tyrosine receptor, to allow the activity of vascular endothelium-derived growth factor, fibroblast growth factor and thrombin (Flk-1), as well as vascular area measurement; Both measures were performed by computerized morphometry. RESULTS: An increase in immunohistochemical expression and vascular area in direct proportion to the interaction was identified; It can be affirmed (ANOVA p < 0.0001), that with the interaction of all the maneuvers the maximum effect is achieved. CONCLUSIONS: It is demonstrated that indirect myocardial revascularization has a specific weight within the integral myocardial revascularization with a real impact on cost-benefit and cost-effectiveness.

Introducción: el objetivo de este trabajo fue identificar si la interacción de los métodos de revascularización miocárdica incrementa el área vascular funcional. Métodos: se realizó un estudio con un diseño factorial de 4x3 en 11 grupos, de cinco ratas por grupo, diez muestras por rata, evaluado a 45 días del posoperatorio, con las diferentes combinaciones quirúrgicas. La magnitud de la interacción fue evaluada tanto por inmunoexpresión del factor vascular de crecimiento derivado del endotelio, factor de crecimiento de fibroblastos y receptor de tirosina, para permitir la actividad del factor vascular de crecimiento derivado del endotelio, factor de crecimiento de fibroblastos y trombina (Flk-1), así como de la medición del área vascular; ambas medidas fueron realizadas por morfometría computarizada. Resultados: se identificó un incremento de la expresión inmunohistoquímica y del área vascular en proporción directa con la interacción; se puede afirmar (ANOVA p < 0.0001), que con la interacción de todas las maniobras se logra el efecto máximo. Conclusiones: se demuestra que la revascularización miocárdica indirecta tiene un peso especifico dentro de la revascularización miocárdica integral con un impacto real en el costo-beneficio y el costo-efectividad.

O-GlcNAc-selective-N-acetyl-beta-D-glucosaminidase activity and mRNA expression in muscle is related to glucosamine-induced insulin resistance.

Glucosamine (GlcN)-induced insulin resistance is associated with an increase in O-linked-N-acetylglucosaminylated modified proteins (O-GlcNAcylated proteins). The role played by O-GlcNAc-selective-N-acetyl-beta-D-glucosaminidase (O-GlcNAcase), which removes O-N-acetyl-glucosamine residues from O-GlcNAcylated proteins, has not yet been demonstrated. We investigated whether GlcN-induced whole-body insulin resistance is related to tissue O-GlcNAcase activity and mRNA expression. GlcN (30 mumol/kg/min) or physiological saline (control) was intravenously infused into Sprague-Dawley rats for 2 h. After GlcN treatment, rats were subjected to the following: intravenous glucose tolerance test, insulin tolerance test or removal of the liver, muscle and pancreas. GlcN was found to provoke hyperglycemia compared to control (8.6 +/- 0.41 vs. 4.82 +/- 0.17 mM, p < 0.001). The insulin resistance index (HOMA-IR) increased (15.76 +/- 1.47 vs. 10.14 +/- 1.41, p < 0.001) and the beta-cell function index (HOMA-beta) diminished (182.69 +/- 22.37 vs. 592.01 +/- 103, p < 0.001). Liver glucose concentration was higher in the GlcN group than in the control group (0.37 +/- 0.04 vs. 0.24 +/- 0.038 mmol/g dry weight, p < 0.001). Insulin release index (insulin/glucose) was less in the GlcN group than in the control (2.2 +/- 0.1 vs. 8 +/- 0.8 at 120 min, p < 0.001). In the GlcN group, muscle O-GlcNAcase activity diminished (0.28 +/- 0.019 vs. 0.36 +/- 0.018 nmol of p-nitrophenyl/mg protein/min, p < 0.001), and K(m) increased (1.51 +/- 0.11 vs. 1.12 +/- 0.1 mM, p < 0.001) compared to the control. In the GlcN group, O-GlcNAcase activity/mRNA expression was altered (0.6 +/- 0.07 vs. 1 +/- 0.09 of control, p < 0.05). In conclusion, O-GlcNAcase activity is posttranslationally inhibited during GlcN-induced insulin resistance.

Effect of parathyroidectomy on cardiac fibrosis and apoptosis: possible role of aldosterone.

BACKGROUND/AIM: It has been demonstrated that parathyroidectomy prevents left ventricular hypertrophy in uremic animals. Although this effect may be mediated by direct actions of parathormone (PTH), it may also be exerted through regulation of profibrotic factors such as aldosterone. In adrenal cortex cell cultures, PTH increases aldosterone release. The objective of this work is to assess the effect of parathyroidectomy on aldosterone levels and on cardiac fibrosis and apoptosis in uremic rats. METHODS: Four groups of rats were studied: C, control; 5/6Nx, 5/6 nephrectomy; PTx, parathyroidectomy, and 5/6NxPTx, 5/6 nephrectomy plus parathyroidectomy. Thirty days after the last surgical procedure the animals were sacrificed. Serum creatinine, ionized calcium, aldosterone, PTH, cardiac weight, fibrosis and apoptosis were measured. RESULTS: Serum creatinine levels were significantly higher in 5/6Nx and 5/6NxPTx groups (1.62 +/- 0.21 and 1.38 +/- 0.15 mg/dl) than in C and PTx groups (0.66 +/- 0.02 and 0.47 +/- 0.01 mg/dl, p < 0.001). Potassium levels were significantly higher in the 5/6Nx and 5/6NxPTx groups (5.2 +/- 0.3 and 5.4 +/- 0.3 mg/dl) than in the C group (4.3 +/- 0.06 mg/dl, p < 0.05). Values in 5/6Nx and 5/6NxPTx groups were not significantly different from each other. PTH levels were significantly higher in the 5/6Nx group (470.5 +/- 156.3 microg/ml) than in the controls (102.3 +/- 14.3 microg/ml). PTH levels in the PTx group (1.78 +/- 0.52 microg/ml) and in the 5/6NxPTx group (81.64 +/- 32.15 microg/ml) were similar to control values. Ionized calcium was lower in PTx and 5/6NxPTx groups (0.80 +/- 0.07 and 0.89 +/- 0.07 mmol/l) as compared with C and 5/6Nx groups (1.14 +/- 0.01 and 0.96 +/- 0.01 mmol/ l, p < 0.01). The heart weight as percentage of the body weight increased significantly in 5/6Nx animals (4.20 +/- 0.15%) compared to the C group (3.41 +/- 0.27%, p < 0.05); parathyroidectomy reversed the heart weight increment in the 5/6NxPTx animals (3.58 +/- 0.16%). Myocardial fibrosis was significantly higher in the 5/6Nx group (12.5 +/- 1.1%) than in the C group (7.3 +/- 1.5%, p < 0.001); in the 5/6NxPTx animals fibrosis returned towards control values (8.9 +/- 0.2%). Myocardial apoptosis rose significantly in 5/6Nx animals (24.3 +/- 1.2%) compared to the C group (6.7 +/- 0.83%, p < 0.001); parathyroidectomy reversed the apoptosis in the 5/6NxPTx animals (10.4 +/- 0.49%). Aldosterone levels increased significantly in the 5/6Nx group (2,461 +/- 257 pg/ml) compared to the C group (703 +/- 81 pg/ml, p < 0.001); in the 5/6NxPTx animals aldosterone levels were below control values (509 +/- 99 pg/ml). CONCLUSIONS: Uremia was associated to myocardial hypertrophy, fibrosis and apoptosis. Surgically induced hypoparathyroidism prevented the development of these disorders. Our results suggest that in the remnant kidney rat model myocardial hypertrophy, fibrosis, and apoptosis are mediated by high circulating aldosterone levels. Aldosterone, in turn, may be regulated by PTH.

[Ovarian denervation and polycystic ovary]. / Denervación y poliquistosis ováricas.

BACKGROUND: Ovarian inervation is limited to the superior pedicle and ovarian artery to loose itself within the gonadal smooth muscle. Hence, it is far from clear how is it that the ovary preserves its communication with hypothalamic and pituitary structures for feedback regulation. There is a lack of precision concerning structures and mechanisms involved in the genesis of polycystic disease. OBJECTIVE: To know the role of inervation associated to hormone stimuli in developing polycystic ovaries. MATERIAL AND METHODS: Groups of Sprague Dawley rats were studied: group 1, whom received cornoil (vehicle) served as controls; group 2 had estradiol valerianate (EV) and group 3 was exposed to phenol for denervation and also received estradiol valerianate (EV). After sacrifice, ovaries were exposed and saved in a formol solution until preparation and staining with hematoxilin-eosin and for immunochemical reaction using specific monoclonal antibodies for nerve tissue (PS-100 & GFAP). RESULTS: Biologic response was considered when follicle dilation was seen under microscopy evaluation. The ovaries with higher follicle development belonged to group 2 (EV) while preserving intrinsic follicular nervous activity as shown by a positive immunoreaction to PS-100 & GFAP. Those denervated and exposed to EV (group 3) did not show significant changes in follicular size resembling controls. CONCLUSIONS: The presence of neural activity is vital for development of cysts and the neural mechanisms involved seemed to lie within the ovarian cells.