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Several studies support the hypothesis that chronic diseases in adulthood might be triggered by events that occur during fetal development. This study examined the consequences of perinatal salt intake on blood pressure (BP) and carbohydrate and lipid metabolism in adult offspring of dams on high-salt [HSD; 8% (HSD2) or 4% (HSD1)], normal-salt (NSD; 1.3%), or low-salt (LSD; 0.15% NaCl) diet during pregnancy and lactation. At 12 wk of age, female Wistar rats were matched with adult male rats that were fed NSD. Weekly tail-cuff BP measurements were performed before, during, and after pregnancy. After weaning, the offspring received only NSD and were housed in metabolic cages for 24-h urine collection for sodium and potassium and nitrate and nitrite excretion measurements. At 12 wk of age, intra-arterial mean BP was measured, a euglycemic-hyperinsulinemic clamp was performed, and plasma lipids and nitrate and nitrite concentrations were determined. Tail-cuff BP was higher during pregnancy in HSD2 and HSD1 than in NSD and LSD dams. Mean BP (mm Hg) was also higher in the offspring of HSD2 (110 Ϯ 5) and HSD1 (107 Ϯ 5) compared with NSD (100 Ϯ 2) and LSD (92 Ϯ 2). Lower glucose uptake and higher plasma cholesterol and triacylglycerols were observed in male offspring from LSD dams (glucose uptake: HSD2 17 Ϯ 4, HSD1 15 Ϯ 3, NSD 11 Ϯ 3, LSD 4 Ϯ 1 mg · kg Ϫ1 · min Ϫ1 ; cholesterol: HSD2 62 Ϯ 6, HSD1 82 Ϯ 11, NSD 68 Ϯ 10, LSD 98 Ϯ 17 mg/dL; triacylglycerols: HSD2 47 Ϯ 15, HSD1 49 Ϯ 12, NSD 56 Ϯ 19, LSD 83 Ϯ 11 mg/dL). In conclusion, maternal salt intake during pregnancy and lactation has long-term influences on arterial pressure, insulin sensitivity, and plasma lipids of the adult offspring. (Pediatr Res 56: 842-848, 2004) Abbreviations BP, blood pressure HSD, high-salt diet HR, heart rate LSD, low-salt diet MBP, mean blood pressure NSD, normal-salt diet NOx, nitrate plus nitrite RAS, renin-angiotensin system tcBP, tail-cuff blood pressure Almost two decades ago, Barker and Osmond (1) proposed that ischemic heart disease could be triggered by events that occur during fetal life and early childhood (1). They showed an association between poor living standard during the perinatal period and ischemic heart disease in adulthood. This lifestyle possibly goes along with intrauterine growth retardation. Despite criticisms about the validity of their observations (2), the association between low birth weight and adult diseases is now further supported by several studies with similar findings (3-6). Moreover, the understanding of the mechanisms of this association represents a challenge for investigators in this area.Intrauterine growth is controlled by a complex interplay of maternal and fetal factors, including circulatory, endocrine, and metabolic systems (7). An increasing number of studies have shown that small modifications in fetal growth may have profound consequences in later life (8 -10).

These data indicate that C4d positive chronic rejection is very common, associated with proteinuria, and has a poor outcome. A larger study is warranted to identify which immunosuppressive regimen may modify the poor course of this entity.

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Gene therapy using VEGF and G-CSF demonstrated a synergistic effect promoting vessel and tissue repair in mouse hind limb ischemia.

Background Granulocyte-colony-stimulating factor (GM-CSF) is a pleiotropic factor for hematopoiesis that stimulates myeloblasts, monoblasts and mobilization of bone marrow stem cells. Therefore, the GM-CSF gene is a potential candidate for vessel formation and tissue remodeling in the treatment of ischemic diseases.

Elevated concentrations of testosterone and its synthetic analogs may induce changes in cardiovascular function. However, the effects of the combination of anabolic/androgenic steroid (AAS) treatment and exercise training on systolic and diastolic cardiac function are poorly understood. In the present study, we aimed to investigate the effects of low-dose steroid treatment (stanozolol) on cardiac contractile parameters when this steroid treatment was combined with exercise training in rats and the effects of chronic steroid treatment on the Frank-Starling (length-tension curves) relationship. Male Wistar rats were randomly assigned to one of four groups: U (untrained), US (untrained and treated with stanozolol 5 mg/kg/week), T (trained, 16 m/min/1 h) and TS (trained and treated with stanozolol 5 mg/kg/week). Continuous exercise training was conducted 5 days/week for 8 consecutive weeks. The speed of the treadmill was gradually increased to a final setting of 16 m/min/1 h. Experiments were divided into two independent series: 1) central hemodynamic analysis for mean arterial blood pressure (MAP) and cardiac output (CO) measurements and 2) isolated papillary muscle preparation in Krebs solution. Stanozolol treatment significantly increased the MAP and the heart size in untrained and trained rats (U 113±2; T 106±2; US 138±8 and TS 130±7 mmHg). Furthermore, stanozolol significantly decreased developed tension and dT/dt (maximal and minimal) in U rats. However, the developed tension was completely restored by training. The Frank/Starling relationship was impaired in rats treated with stanozolol; however, again, training completely restored diastolic function. Taken together, the present data suggest that AAS treatment is able to decrease cardiac performance (systolic and diastolic functions). The combination of stanozolol and physical training improved cardiac performance, including diastolic and systolic functions, independent of changes in central hemodynamic parameters. Therefore, changes in ventricular myocyte calcium transients may play a cardioprotective role.

A novel, efficient transfection method, based on ultrasound and hydrodynamics, has been developed to transfect heart tissue with plasmid DNA. An ultrasound probe was aimed at the heart of anesthetized rats for 30 sec, at an intensity of 1 MHz and 2 W/cm2. The aorta was clamped and a phosphate-buffered saline (PBS) solution containing pSV-LacZ was quickly injected into the left ventricle. Each animal was maintained in this condition for 20 sec, and then the clamp was opened and the needle was removed. Electrocardiography, performed after 4 weeks, showed mild or no sign of ischemia in all groups. Visual evaluation of heart tissue samples from rats that received 100 microg of pSV-LacZ in 100 microl had only a few blue cells, indicating transfection, and those that received only PBS had no blue cells. However, all heart tissue samples from rats transfected with 100 to 500 microg of pSV-LacZ in 200 microl, or with 200 to 500 microg of pSV-LacZ in 100 micro had many blue cells. The base and epicardium of the heart tissue samples had many more blue cells than did the rest of the samples. Histological results, based on staining with hematoxylin and eosin, showed similar results between control and transfected groups. Therefore, we concluded that gene delivery by plasmid vector in association with ultrasound and hydrodynamics was highly effective in transfecting rat heart.