Selenium in combination with a tomato lipid extract as a therapy for benign prostatic hyperplasia and its alterations in rats with induced BPH.

Benign prostatic hyperplasia (BPH) is the most common adenoma in old men. Tomatoes are a rich source of bioactive compounds that, as well as selenium (Se), possess antioxidant and antiproliferative activity. The aim was to evaluate the therapeutic effect of Se in combination with a tomato extract in aged rats with BPH. Aged male Wistar rats were divided in the following groups (n = 10 rats/group): Control (C), BPH, BPH + Finasteride (BPH + F), BPH + Tomato Lipidic Extract (BPH + E), BPH + Selenium (BPH + S) and BPH plus E plus S (BPH + E + S). After 4 weeks of treatment, prostate weight, diuresis, antioxidants enzymes, prooxidants and inflammatory markers, growth factors and androgens were determined. BPH + E + S reduced prostate weight by 59.29% and inhibited growth by 99.35% compared to BPH + F which only decreased weight and inhibited growth by 15.31% and 57.54%, respectively. Prooxidant markers were higher with BPH + F (49.4% higher vs. BPH), but BPH + E + S decreased these markers (94.27% vs. BPH) and increased antioxidant activity. Finally, diuresis was higher with the BPH + E + S combination and markers of inflammation and growth factors were significantly lower with respect to BPH + F. Our findings provide a beneficial and protective therapeutic option of E + S directed against androgens, oxidative stress and inflammation that regulates cell proliferation in the prostate gland.

Tomato lipidic extract plus selenium decrease prostatic hyperplasia, dihydrotestosterone and androgen receptor expression versus finasteride in rats.

PURPOSE: Evaluate the therapeutic effect of a tomato lipidic extract (STE) in combination with selenium (Se) on rats with prostatic hyperplasia (PH) and to observe its possible mechanisms of action and synergism versus finasteride. MATERIALS AND METHODS: 54 male Wistar rats of nine weeks old were divided in Control (C), PH, Finasteride (F), STE, Se, F + STE, F + Se, STE + Se and F + STE + Se with testosterone enanthate (except C). After 4 weeks of treatment administration, prostate weight, bladder weight, diuresis, prooxidant and antioxidant activity, dihydrotestosterone (DHT), androgen receptor (AR) expression and anatomopathological analysis were determined. RESULTS: STE + Se decreased prostate weight 53.8% versus 28% in F group, also STE + Se decreased significatively glandular hyperplasia, prooxidant activity, DHT and AR expression and increased diuresis and antioxidant activity versus finasteride which increased MDA in prostate. CONCLUSIONS: These results demonstrate a greater therapeutic and beneficial effect of tomato lipidic extract in combination with Se in young rats with PH with respect to finasteride without increase prooxidant activity.

Combined fructose and sucrose consumption from an early age aggravates cardiac oxidative damage and causes a dilated cardiomyopathy in SHR rats.

Obesity increases the risk of arterial hypertension in young adults and favors an early-onset cardiomyopathy by generating oxidative stress. In this sense, indiscriminate consumption of sucrose and fructose sweetened beverages from early ages causes obesity, however its consequences on the heart when there is a genetic predisposition to develop hypertension are not clear. We compared the effects of sucrose, fructose, and their combination in weanling male spontaneously hypertensive rats to determine the relationship between genetic hypertension, obesity, and consumption of these sugars on the degree of cardiac hypertrophy, oxidative stress and Ca2+/calmodulin dependent protein kinase II delta oxidation. Histological, biochemical, and Western blot studies were performed 12 weeks after treatment initiation. We found that chronic consumption of sucrose or fructose leads to obesity, exacerbates genetic arterial hypertension-induced metabolic alterations, and increases cardiac oxidative stress, Ca2+/calmodulin dependent protein kinase II delta oxidation and cardiac hypertrophy. Nonetheless, when sucrose and fructose are consumed together, metabolic alterations worsen and are accompanied by dilated cardiomyopathy. These data suggest that sucrose and fructose combined consumption starting from maternal weaning in rats with genetic predisposition to arterial hypertension accelerates the progression of cardiomyopathy resulting in an early dilated cardiomyopathy.

Consumption of combined fructose and sucrose diet exacerbates oxidative stress, hypertrophy and CaMKIIδ oxidation in hearts from rats with metabolic syndrome.

The prevalence of the metabolic syndrome (MetS) and its cardiac comorbidities as cardiac hypertrophy (CH) have increased considerably due to the high consumption of carbohydrates, such as sucrose and/or fructose. We compared the effects of sucrose (S), fructose (F) and their combination (S + F) on the development of MetS in weaned male Wistar rats and established the relationship between the consumption of these sugars and the degree of cardiac CH development, oxidative stress (OS) and Calcium/calmodulin-dependent protein kinase type II subunit delta oxidation (ox-CaMKIIδ). 12 weeks after the beginning of treatments with S, F or S + F, arterial pressure was measured and 8 weeks later (to complete 20 weeks) the animals were sacrificed and blood samples, visceral adipose tissue and hearts were obtained. Biochemical parameters were determined in serum and cardiac tissue to evaluate the development of MetS and OS. To evaluate CH, atrial natriuretic peptide (ANP), CaMKIIδ and ox-CaMKIIδ were determined by western blot and histological studies were performed in cardiac tissue. Our data showed that chronic consumption of S + F exacerbates MetS-induced CH which is related with a higher OS and ox-CaMKIIδ.

Topical capsaicin cream with moderate exercise protects against hepatic steatosis, dyslipidemia and increased blood pressure in hypoestrogenic obese rats.

BACKGROUND: The aim of this study was to evaluate the effects of capsaicin (Cap), moderate exercise (Ex), and their combination on arterial blood pressure (BP) and metabolic complications in hypoestrogenic (HE) obese (HEOb) rats. Female Wistar rats were ovariectomized and given 300 g L-1 sucrose solution (HEOb), or purified water (HE) ad libitum, for 28 weeks. After shaving the abdominal skin, cold cream vehicle was applied to sedentary (Sed) and exercise (Ex) groups, and 0.75 g kg-1 Cap cream was applied to Ex groups. Ex groups ran on a treadmill every day for 20 min at speeds from 0.15 to 0.3 m s-1 . For combination groups (Cap + Ex), topical Cap was applied 90 min before Ex. The treatments were performed for 6 weeks, and BP was recorded before and at the end of the experimental protocol. The animals were killed by decapitation, and blood and tissues were obtained to perform oxidative profile, as well as to undertake biochemical and histologic studies. RESULTS: Compared with individual treatments, the combined therapy (Cap + Ex) in HEOb rats caused a higher reduction in the caloric intake, body weight, abdominal fat percentage, oxidative stress, and hepatic steatosis. In HEOb groups, Cap was the only treatment that reduced BP and prevented dyslipidemia and oxidative stress. CONCLUSION: The present data show that Cap improves the metabolic alterations induced by obesity and hypoestrogenism, suggesting that Cap can be considered as an excellent candidate for therapy of these clinical conditions. © 2020 Society of Chemical Industry.

Characterization of free fatty acid receptors expression in an obesity rat model with high sucrose diet.

INTRODUCTION/AIMS: In recent years, it has been shown that free fatty acids receptors (FFAR) of whose function in the cell surface plays a significant role in the regulation of cell function and nutrition as well are activated by various endogenous ligands, but mainly by fatty acids. Within FFAR of our interest are GPR 41, 43 and 120. The functions of these receptors are varied and dependent on the tissue where they are. The activation and signaling of these receptors, FFAR, are involved in many physiological processes, and currently the target of many drugs in metabolic disorders like obesity, diabetes and atherosclerosis. MATERIAL AND METHODS: Obesity was induced with hypercaloric diet (HD) in male Wistar rats for 20 weeks (n = 10). At the end, adipose tissue (abdominal and subcutaneous) was taken to perform assays for relative quantification mRNA expression by end-point RT-PCR and protein level expression by Western blot. RESULTS: These present data have shown for the first time that total mRNA isolation and protein expression from both adipose tissues (abdominal and subcutaneous) of rat in obesity condition yield significative statistical difference among the control versus obese groups, showing that the diet high in carbohydrates modifies the total presence of mRNA and protein level expression of the receptors GPR41, 43 and 120. CONCLUSIONS: Further comparative methods are in process to clarify whether or not the obesity changes the functional receptors in these two tissues for new pharmacological approaches.

Adipokines, asymmetrical dimethylarginine, and pulmonary function in adolescents with asthma and obesity.

OBJECTIVE: This study was to investigate whether the metabolic abnormalities of adipokines and asymmetrical dimethylarginine (ADMA) associate with pulmonary function deficits in adolescents with obesity and asthma. METHODS: This study enrolled 28 obese adolescents with asthma, 46 obese adolescents without asthma, 58 normal-weight adolescents with asthma, and 63 healthy control subjects. Serum levels of leptin, high-molecule-weight (HMW) adiponectin, retinol binding protein 4 (RBP4), asymmetrical dimethylarginine (ADMA), and pulmonary function were qualified. RESULTS: The obese subjects had higher levels of leptin and ADMA but lower levels of HMW adiponectin than the normal-weight subjects with or without asthma. The subjects with asthma had higher levels of RBP4 than those without asthma. The obese adolescents with asthma had lowest forced expiratory lung volume in the first second (FEV1)/forced vital capacity (FVC) ratio among the four study groups. In all the study subjects and in the subjects with asthma alone, the FEV1/FVC ratio associated negatively with leptin, however, such association was rendered non-significant when adjusted for BMI. The pulmonary function deficits associated inversely with BMI percentile in the subjects with asthma. However, the decreased FEV1/FVC ratio was not correlated with HMW adiponectin, RBP4 or ADMA. CONCLUSIONS: Our present study confirmed obstructive pattern of pulmonary function characterized by the reduced FEV1/FVC ratio in the obese adolescents with asthma. These pulmonary deficits were associated inversely with the increased BMI percentile.

Abnormality of adipokines and endothelial dysfunction in Mexican obese adolescents with insulin resistance.

PURPOSE: The aim of this study was to investigate the possible relationship among insulin resistance (IR), endothelial dysfunction, and alteration of adipokines in Mexican obese adolescents and their association with metabolic syndrome (MetS). MATERIALS AND METHODS: Two hundred and twenty-seven adolescents were classified according to the body mass index (BMI) (control: N=104; obese: N=123) and homeostasis model of the assessment-insulin resistance index (HOMA-IR) (obese with IR: N=65). The circulating concentrations of leptin, adiponectin, soluble intercellular adhesion molecule-1 (sICAM-1), and IR were determined by standard methods. RESULTS: The obese adolescents with IR presented increased presence of MetS and higher circulating concentrations in sICAM-1 in comparison with the obese subjects without IR. The lowest concentrations of adiponectin were observed in the obese with IR. In multivariate linear regression models, sICAM-1 along with triglycerides, total cholesterol, and waist circumference was strongly associated with HOMA-IR (R2=0.457, P=0.008). Similarly, after adjustment for age, BMI-SDS, lipids, and adipokines, HOMA-IR remained associated with sICAM-1 (R2=0.372, P=0.008). BMI-SDS was mildly associated with leptin (R2=0.176, P=0.002) and the waist circumference was mild and independent determinant of adiponectin (R2=0.136, P=0.007). CONCLUSIONS: Our findings demonstrated that the obese adolescents, particularly the obese subjects with IR exhibited increased presence of MetS, abnormality of adipokines, and endothelial dysfunction. The significant interaction between IR and endothelial dysfunction may suggest a novel therapeutic approach to prevent or delay systemic IR and the genesis of cardiovascular diseases in obese patients.

Beneficial effects of lipidic extracts of saladette tomato pomace and Serenoa repens on prostate and bladder health in obese male Wistar rats.

BACKGROUND: Obesity is associated with increased risk of a number of serious medical conditions, including urological disorders. This study investigated the effect of lipidic extracts of saladette tomato pomace (STP) and Serenoa repens (SR) on the prostate and bladder in a rat obese model induced by high-carbohydrate diet. RESULTS: High-sucrose-fed rats showed higher prostate weight as well as increased contractility and stromal and epithelial hyperplasia in the prostate. Treatment with STP and SR improved contractility and diminished hyperplasia and hypertrophy in the prostate. Obese animals also showed impaired bladder contractility, but neither extract reversed this deterioration. In the histological study, a disarray in the process of smooth muscle cell proliferation with non-parallel fibers was observed; interestingly, treatment with STP and SR led to improvement in this derangement. CONCLUSION: These findings indicated impaired contractility and hyperplasia in the prostate and bladder of obese rats induced by high sucrose. STP and SR could enhance prostate function by reducing contractility and hyperplasia and improve smooth muscle fiber structure and decrease cell proliferation in the bladder, suggesting their possible health-beneficial effects on lower urinary tract symptoms. © 2017 Society of Chemical Industry.

Effect of Serenoa Repens on Oxidative Stress, Inflammatory and Growth Factors in Obese Wistar Rats with Benign Prostatic Hyperplasia.

Serenoa repens has been widely used to treat benign prostatic hyperplasia and lower urinary tract symptoms; however, most of the studies have been conducted in individuals with normal weight and not obese. In this study, the effects of a lipidic extract of S. repens, in markers of oxidative stress, inflammation, and growth factors, in obese rats with testosterone-induced prostatic hyperplasia, were investigated. Total nitrites, malondialdehyde, total glutathione, superoxide dismutase (SOD), and catalase activity were measured; in addition, assays for inflammatory cytokines TNF-α, IL-1ß, IL-6 and the growth factors basic fibroblast growth factor (FGFb) and vascular endothelial growth factor (VEGF) were performed. The obese rats had a higher prostate weight compared with controls. S. repens significantly decreased prostate weight, total nitrites, and malondialdehyde; improved total glutathione, SOD, and catalase activity; and significantly reduced inflammatory (TNF-α, IL-1ß and IL-6) and growth factors (VEGF and FGFb). S. repens showed high antioxidant and antiinflammatory activity in obese rats, suggesting that their use could be beneficial in the treatment of benign prostatic hyperplasia.

Effect of six-month lifestyle intervention on adiponectin, resistin and soluble tumor necrosis factor-α receptors in obese adolescents.

The aim of this study was to evaluate the effect of a six-month lifestyle intervention on adiponectin, resistin, and two soluble forms of tumor necrosis factor-α receptor (sTNFR) in obese adolescents. A total of 54 obese adolescents aged 10 to 16 years completed the program. Twenty-four adolescents with normal weight at baseline were used as a control group. Our results demonstrated that obese adolescents had abnormal lipid profile, homeostasis model assessment (HOMA) index, adiponectin level (5.6 ± 2.7 vs. 7.6 ± 2.9 µg/mL, p = 0.005) as well as resistin level (31.0 ± 9.0 vs. 24.3 ± 8.5 ng/mL, p = 0.003), whereas levels of both sTNFRs were similar to those in normal weight subjects. After the six-month lifestyle intervention, obese adolescents had a slight but significant drop in standard deviation score-body mass index (SDS-BMI), a significant decrease in waist circumference, total cholesterol, triglycerides, HOMA index, as well as resistin, and a significant increase in adiponectin and high-density lipoprotein-cholesterol. In adolescents without decreased SDS-BMI, no change was observed in adipokines. Changes in adiponectin correlated negatively with changes in waist circumference (r = -0.275, p = 0.044). Changes in resistin correlated positively with changes in triglycerides (r = 0.302, p = 0.027). The study demonstrated the increase of resistin and the decrease of adiponectin in obese adolescents. Lifestyle intervention improved adipokine abnormalities in obese subjects.

Whole tomato lipidic extract improved sperm quality in obese rats induced by a high-carbohydrate diet.

BACKGROUND: Obesity represents a risk in the development of metabolic and oxidative stress (OS), as well as in male infertility. There is still no pharmacological treatment for obesity-induced male infertility, but the use of natural antioxidants has been proposed as a treatment. OBJECTIVE: The aim of this work is to evaluate the effect of a whole tomato lipid extract on rats that decreased their fertility and spermatogenesis after being induced obese with a high carbohydrate diet. MATERIALS AND METHODS: One hundred fourteen male Wistar rats of 12 weeks of age were used. Two groups were randomly formed non-obese control group (C, n = 54) and obese group (Ob, n = 54) that received 30% w/v sucrose solution for 3 months. Subsequently, the C and Ob group were divided into two groups: vehicle (C-Vh and Ob-Vh) that received corn oil as vehicle and tomato lipid extract (C-Ex and Ob-Ex) that received whole tomato lipid extract. The groups that received a hypercaloric diet had a gain in visceral and retroperitoneal adipose tissue, an increase in total cholesterol and triglyceride levels, increased OS in the testis, and lesions in testicular histology, as well as a reduction in testicular size and sperm quality parameters (motility, viability, and concentration). RESULTS: Treatment with whole tomato lipid extract significantly decreased the weight of gonadal adipose tissue and OS, maintained testicular size, showed a significant increase in sperm quality parameters and improved histology of seminiferous tubules. CONCLUSIONS: These results demonstrate a greater therapeutic and beneficial effect of the tomato lipid extract on sperm quality parameters in obese rats and therefore on fertility.

Oxidative stress in cardiomyocytes contributes to decreased SERCA2a activity in rats with metabolic syndrome.

Ca(+) mishandling due to impaired activity of cardiac sarco(endo)plasmic reticulum Ca(2+) ATPase (SERCA2a) has been associated with the development of left ventricular diastolic dysfunction in insulin-resistant cardiomyopathy. However, the molecular causes underlying SERCA2a alterations induced by insulin resistance and related metabolic disorders, such as metabolic syndrome (MetS), are not completely understood. In this study, we used a sucrose-fed rat model of MetS to test the hypothesis that decreased SERCA2a activity is mediated by elevated oxidative stress produced in the MetS heart. Production of ROS and cytosolic Ca(2+) concentration were recorded in left ventricular myocytes using confocal imaging. The level of SERCA2a oxidation was determined in left ventricular homogenates by biotinylated iodoacetamide labeling. Compared with control rats, sucrose-fed rats exhibited several characteristics of MetS, including central obesity, insulin resistance, hyperinsulinemia, and hypertriglyceridemia. Moreover, relative to myocytes from control rats, myocytes from MetS rats exhibited elevated basal production of ROS accompanied by slowed cytosolic Ca(2+) removal, reflected by prolonged Ca(2+) transients. The slowed cytosolic Ca(2+) removal was associated with a significant decrease in SERCA2a-mediated Ca(2+) reuptake and increased SERCA2a oxidation. Importantly, myocytes from MetS rats treated with the antioxidant N-acetylcysteine showed normal ROS levels and SERCA2a-mediated Ca(2+) reuptake as well as accelerated cytosolic Ca(2+) removal. These data suggest that elevated oxidative stress may induce oxidative modifications on SERCA2a leading to abnormal function of this protein in the MetS heart.

Lipidic extract of whole tomato reduces hyperplasia, oxidative stress and inflammation on testosterone-induced BPH in obese rats.

PURPOSE: Tomato is an important source of lycopene, a carotenoid that has been emerging as a natural preventive agent for prostate disease. Moreover, tomato contains other components with a wide range of physiological properties, but their potential beneficial effects on prostatic hyperplasia (PH) during obesity have not been completely established. In this study, we compared the effect of a lipidic extract of tomato saladette (STE) with Serenoa repens (SR) on obese rats with PH. METHODS: Forty-eight Wistar rats were divided in Control (C) and Obese (Ob) treated without (n = 12) and with (n = 36) testosterone enanthate (TE), once a week for 8 weeks to induce PH. After 4 weeks, SR and STE were administered. Biochemical parameters, oxidative stress markers and inflammatory cytokines production were determined. RESULTS: TE increased prostate weight and caused prostatic hyperplasia in C group, and these effects were exacerbated by obesity. SR and STE reverted the increase in prostate weight and hyperplasia caused by TE in C and Ob groups. Obesity increased LDL, TGs, NOx and MAD, but decreased HDLc, GSx, SOD and CAT. SR reverted the effects of obesity, but these were significantly reduced and HDLc increased with STE. Obesity and TE increased TNFα, IL-1ß and IL-6 levels, but these were partially reverted by STE compared with SR. CONCLUSIONS: Excess of fat tissue increases the alterations by PH. STE diminishes these alterations compared with SR, suggesting its beneficial effect to improve prostate function. Whole tomato lipid extract could serve as sole therapy or as an adjunct to pharmacological treatment for PH.

Oxidative stress in early metabolic syndrome impairs cardiac RyR2 and SERCA2a activity and modifies the interplay of these proteins during Ca2+ waves.

We investigated how oxidative stress (OS) alters Ca2+ handling in ventricular myocytes in early metabolic syndrome (MetS) in sucrose-fed rats. The effects of N-acetyl cysteine (NAC) or dl-Dithiothreitol (DTT) on systolic Ca2+ transients (SCaTs), diastolic Ca2+ sparks (CaS) and Ca2+ waves (CaW), recorded by confocal techniques, and L-type Ca2+ current (ICa), assessed by whole-cell patch clamp, were evaluated in MetS and Control cells. MetS myocytes exhibited decreased SCaTs and CaS frequency but unaffected CaW propagation. In Control cells, NAC/DTT reduced RyR2/SERCA2a activity blunting SCaTs, CaS frequency and CaW propagation, suggesting that basal ROS optimised Ca2+ signalling by maintaining RyR2/SERCA2a function and that these proteins facilitate CaW propagation. Conversely, NAC/DTT in MetS recovered RyR2/SERCA2a function, improving SCaTs and CaS frequency, but unexpectedly decreasing CaW propagation. We hypothesised that OS decreases RyR2/SERCA2a activity at early MetS, and while decreased SERCA2a favours CaW propagation, diminished RyR2 restrains it.

Plasminogen activator inhibitor-1, fibrinogen, and lung function in adolescents with asthma and obesity.

BACKGROUND: Obesity promotes a low-grade systemic inflammatory state that may act on the lung to exacerbate asthma. There is little information on the relationship between systemic inflammation and lung function in children and adolescents. OBJECTIVES: To explore the relationship among fibrinogen, plasminogen activator inhibitor-1 (PAI-1), lung function in adolescents with the presence of asthma, and/or obesity. METHODS: Totally 178 adolescents (boys and girls) were involved; four groups were divided according to their diagnosis: non-obese and non-asthmatic controls (n = 38), non-obese asthmatics (n = 31), obese non-asthmatics (n = 62), obese asthmatics (n = 47). The levels of PAI-1 and fibrinogen were determined in blood samples. The lung function was evaluated with spirometry by measuring forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and forced expiratory flows between 25 and75% (FEF(25-75%)). RESULTS: Compared to healthy controls, obese adolescents with or without asthma show higher levels of fibrinogen (289.2 ± 61.5, 328.4 ± 54.9, and 324.9 ± 68.9 mg/dL, respectively), PAI-1 (36.0 ± 17.3, 53.2 ± 22.3, and 52.6 ± 24.7 ng/mL, respectively), and the reduced FEV1/FVC ratio (87.7 ± 7.7, 81.6 ± 8.6, and 81.7 ± 6.9, respectively). In the whole studied subjects, FEV1/FVC ratio shows significant inverse correlation with PAI-1 (r = -0.185), fibrinogen (r = -0.157), body mass index (BMI; r = -0.303), insulin(r = -0.198), and HOMA (r = -0.173). In the 78 asthmatic subjects, FVC correlates positively with BMI. CONCLUSION: Our data demonstrate that the degree of systemic inflammation and the degree of obesity in the whole studied adolescents groups correlate negatively with lung function, suggesting an obstructive pulmonary pattern. Further studies are needed to identify the pathophysiological mechanism for such association.

Effect of losartan on vascular function in fructose-fed rats: the role of perivascular adipose tissue.

Recent studies have shown the effect of perivascular adipose tissue (PVAT) on the regulation of vascular function; however, its role in the model of metabolic syndrome remains unclear. The aim of this study was to examine the effect of losartan on PVAT-derived vascular dysfunction in fructose-induced hypertensive rats. Rats were fed with either water, 10% fructose, or 10% fructose with 10mg/kg losartan for 8 weeks. In the isolated aorta with PVAT and endothelium, contraction induced by norepinephrine (NE) was more potent in fructose-fed rats compared to control rats. Losartan normalized blood pressure, insulin resistance, and NE-induced vasoconstriction in fructose-fed rats. In the aortic rings with/without endothelium and with/without PVAT, losartan could not improve the acetylcholine-induced relaxation in fructose-fed rats. The observation suggested that losartan partly improved the PVAT-associated vascular regulation in fructose-induced hypertensive rats.

Acute, subacute and chronic effect of cyclosporin-A on mean arterial pressure of rats with severe spinal cord contusion.

Cyclosporin-A (CsA) protects and regenerates the neural tissue after spinal cord (SC) injury. These beneficial effects are achieved when CsA is administered at a dose of 2.5mg/kg/12h during the first 2 days after lesion. In view of these observations, it is realistic to envision that, CsA could be tested in SC-clinical trials. Since CsA is a drug strongly related to hypertension, results imperative to evaluate experimentally the effect of the above CsA-dose regimen on blood pressure. For this purpose, one hundred and twenty adult rats were subjected (10 groups) or not (10 groups) to SC-injury. Five injured and five Sham-operated groups received CsA. The remaining groups received only vehicle. Mean arterial pressure (MAP) was recorded from these animals at acute (6 and 24h post surgery; p.s.), subacute (96h), or chronic (30 days) stages of injury. In the latter, the therapy (CsA or vehicle) was administered only during the first 2 days p.s. or daily during 30 days of follow-up. The results of this study showed that SC-injury by itself induces a significant decrease of MAP during the acute and subacute phases of injury. CsA therapy was able to reestablish MAP parameters to control values in these phases. Regardless the therapy, a reestablishment of MAP was observed in chronic stages. Only the daily administration of CsA induced a significant increase in MAP, however; such variation remained into the normal ranges of MAP for rats. The potential benefits offered by CsA support its usefulness after SC-injury.

Synthesis and biological activity of furostanic analogues of brassinosteroids bearing the 5alpha-hydroxy-6-oxo moiety.

Two furostanic analogues of brassinosteroids bearing the 5alpha-hydroxy-6-oxo moiety were synthesized and their biological activity studied using the bean second internode elongation test. One of the compounds produced significant stimulation at doses of 2.5 and 5ng/plant.

Indorenate improves motor function in rats with chronic spinal cord injury.

The effect of indorenate (5-methoxytryptamine, beta-methyl carboxylate hydrochloride), a 5-HT1A agonist, was investigated on the motor performance of rats with chronic spinal cord injury. Four months after a ninth thoracic vertebrae spinal cord contusion, 29 rats were randomly allocated into two groups: saline solution and indorenate-treated animals with daily doses incremented at weekly intervals. The locomotor performance of all rats was measured by the Basso, Beattie, and Bresnahan (BBB) rating scale. The results showed that at the end of the treatment, the motor activity of indorenate group was significantly better than that presented by saline solution group. The 80% of indorenate, (against 15% of saline solution) did not show detriment on motor activity. When we analysed the motor activity of rats with basal BBB lower than 10, a significant improvement of motor recovery in indorenate-treated animals was observed. The benefits observed in locomotor function at low doses followed by increasing doses could be associated with pharmacological treatment by indorenate, a well-known 5-HT1A receptor agonist. Our results suggest a potential mechanism by which serotonergic agents may improve motor function in rats with chronic spinal cord injury.