Norepinephrine-induced hypertension dilates vasospastic basilar artery after subarachnoid haemorrhage in rabbits

Background  Vasopressor-induced hypertension is routinely indicated for prevention and treatment of cerebral vasospasm (CVS) after subarachnoid haemorrhage (SAH). Mechanisms underlying patients’ clinical improvement during vasopressor-induced hypertension remain incompletely understood. The aim of this study was to evaluate angiographic effects of normovolaemic Norepinephrine (NE)-induced hypertension therapy on the rabbit basilar artery (BA) after SAH. Methods  Cerebral vasospasm was induced using the one-haemorrhage rabbit model; sham-operated animals served as controls. Five days later the animals underwent follow-up angiography prior to and during NE-induced hypertension. Changes in diameter of the BA were digitally calculated in mean μm ± SEM (standard error of mean). Findings  Significant CVS of 14.2% was documented in the BA of the SAH animals on day 5 compared to the baseline angiogram on day 0 (n = 12, p < 0.01), whereas the BA of the control animals remained statistically unchanged (n = 12, p > 0.05). During systemic administration of NE, mean arterial pressure increased from 70.0 ± 1.9 mmHg to 136.0 ± 2.1 mmHg in the SAH group (n = 12, p < 0.001) and from 72.0 ± 3.1 to 137.8 ± 1.3 in the control group (n = 12, p < 0.001). On day 5 after SAH, a significant dilatation of the BA in response to norepinephrine could be demonstrated in both groups. The diameter of the BA in the SAH group increased from 640.5 ± 17.5 μm to 722.5 ± 23.7 μm (n = 12, p < 0.05; ). In the control group the diameter increased from 716.8 ± 15.5 μm to 779.9 ± 24.1 μm (n = 12, p < 0.05). Conclusion  This study demonstrated that NE-induced hypertension causes angiographic dilatation of the BA in the SAH rabbit model. Based on these observations, it can be hypothesised that clinical improvement during vasopressor-induced hypertension therapy after SAH might be explained with cerebral vasodilatation mechanisms that lead to improvement of cerebral blood flow. Volker Neuschmelting and Ali-Reza Fathi contributed equally to the study.     

Value of Plasma Level of Endothelin-1 and Nitric Oxide in Diabetic Nephropathy

Endothelial dysfunction is the central pathophysiologic denominator for all microvascular complications of diabetes, including nephropathy. Abnormalities of endothelin-1 and nitric oxide (NO) modulate renal structure and function in diabetes. We study the role of endothelin-1 and NO in the diabetic kidney. This study includes a total of 60 type-2 diabetic patients and 20 healthy subjects as a control group (group 1). Diabetics were classified into three groups. Group 2 included 20 patients without microalbuminuria, group 3 included 20 patients with microalbuminuria, and group 4 included 20 patients with macroalbuminuria. All individuals were subjected to history taking, physical examination, urine analysis, HbA1C test, kidney function tests, abdominal ultrasonography, and evaluation of urinary albumin concentration, nitric oxide levels, and plasma endothelin-1 (ET-1) levels. Our results showed an elevated plasma level of endothelin-1 of 4.09 ± 0.32, 5.04 ± 0.20, and 5.74 ± 0.11 pg/ml for group 2, 3, and 4, respectively, an elevated plasma level of nitric oxide in type-2 diabetic patients with early stages of diabetic nephropathy, and a decreased level in late stages of diabetic nephropathy of 40.08 ± 1.66, 46.11 ± 1.75, and 31.17 ± 2.16 μmol/l for group 2, 3, and 4, respectively. There was a statistically significant difference between all groups and the control group regarding NO and ET-1 (p < 0.001 and p < 0.001, respectively). The enhanced NO production may contribute to hyperfiltration in early diabetic nephropathy. ET-1 may have a role in microvascular damage in diabetics. Targeting the ET-1 system might be potentially beneficial in preventing and/or treating kidney disease in diabetics.     

MR angiography in patients with subarachnoid hemorrhage: adequate to evaluate vasospasm-induced vascular narrowing?

The diagnosis of cerebral vasospasm (CVS) following subarachnoid hemorrhage (SAH) is still challenging. We evaluate the accuracy of time of flight MR angiography (TOF-MRA) to assess the arterial diameters of the circle of Willis in SAH patients with suspected CVS. MR examinations (1.5 Tesla) including 3D TOF-MRA with maximum intensity projections (MIP) and digital subtraction angiography (DSA) were performed within 24 h in 21 patients with acute aneurysmal SAH and suspicion of CVS. Arterial diameters of the circle of Willis including the distal internal carotid artery (ICA) were measured as ratios to the extradural ICA in standard projections. The diagnosis of CVS was established by comparing the luminal size of baseline and follow-up DSA. The correlation between the arterial ratios measured on MIP angiograms and on follow-up DSA was assessed with Pearson's linear regression analysis. Arterial ratios on MIP angiograms were categorized as correct, overestimated, and underestimated compared to the ratios on follow-up DSA. Pearson's correlation coefficient between the ratios of MIP angiograms and DSA was r = 0.5799 and the regression coefficient was b = 0.4775. Highest correlation was found for the category of severe CVS (r = 0.8201). Of all MIP angiograms, 34.9% showed consistent results compared to the DSA, while 44.2% of MIP images overestimated the vascular narrowing. Standard MIP angiograms from TOF-MRA are not accurate to assess vascular narrowing in patients with suspected CVS after aneurysmal SAH. The multifocal arterial stenoses in CVS may induce severe changes in blood flow dynamics, which compromise the diagnostic accuracy of the TOF-MRA.     

Platelet-Derived Growth Factor (PDGF-AB) like Immune Reactivity in Serum and in Cerebral Spinal Fluid Following Experimental Subarachnoid Haemorrhage in Dogs

Summary  The aim of this study was to evaluate the following questions: Can the platelet-derived growth factor (PDGF-AB) be identified in the serum and cerebro spinal fluid (CSF) of dogs? Is there an increase in the concentration of PDGF-AB following experimental subarachnoid haemorrhage (SAH)? Is the increase in concentration related to the angiographic cerebral vasospasm of the basilar artery. The “double haemorrhage” model was applied in seven dogs to produce experimental SAH with determination of angiographic vasospasm in the basilar artery. Blood and CSF samples were taken on the first, third and eighth days. The analyses were performed with an ELISA human PDGF-AB antibody kit (quantikine human PDGF-AB, R&D Systems, Minneapolis, USA).  The average PDGF-AB base value in the serum on the day before the SAH was 410.77±177.56 pg/ml, in the CSF it was 6.43±3.19 pg/ml. There was a significant (p=0.05) increase in the concentration of PDGF-AB (third day 717.35 pg/ml, eighth day 918.07 pg/ml) in the serum of all animals. No significant increase was found in the CSF samples of any animal. In summary, a PDGF-AB like immune reactivity was found in the serum of dogs with the human PDGF-AB ELISA kit and the concentration of PDGF-AB in the serum increased after experimental SAH but not in CSF, but there was no relationship between the increase in PDGF-AB serum concentration and angiographic vasospasm.     

不同时间浅低温对蛛网膜下腔出血犬脑血管痉挛的影响

目的 探讨不同时间浅低温对蛛网膜下腔出血犬脑血管痉挛的影响.方法 成年健康犬30只,雌雄不拘,体重14～20 kg,采用枕骨大孔二次注血法制备犬蛛网膜下腔出血模型.随机分为5组(n=6),人工脑脊液组(ACSF组):枕骨大孔处注入ACSF 0.5 ml/ks;蛛网膜下腔出血组(SAH组):制备蛛网膜下腔出血模型,维持直肠温度38～39℃;不同时间浅低温组(H_(1～3)组):在第2次注血后分别立即实施8、16和32 h浅低温(33.5℃),随后复温至38～39℃.于第1次注血或注入ACSF前和第2次注血或注入ACSF 5、12和19 d时行整体功能分级(OPC),并采用ELISA法和硝酸还原酶法分别测定血浆和脑脊液内皮素-1(ET-1)和一氧化氮(NO)代谢产物NO_2~-/NO_3~-的浓度,采用CT血管造影动态测量脑基底动脉直径.结果 与ACSF组比较,SAH组和H_1,2组OPC分级升高,血浆和脑脊液ET-1浓度升高,NO_2~-/NO_3~-浓度降低,基底动脉直径减小(P＜0.05),H_3组上述指标差异无统计学意义(P＞0.05);与SAH组比较,H_2,3组OPC分级降低,血浆和脑脊液ET-1浓度降低,NO_2~-/NO_3~-浓度升高,基底动脉直径增大(P＜0.05),H_1组各时点上述指标差异无统计学意义(P＞0.05);与H_2组比较,H_3组血浆和脑脊液ET-1浓度降低,NO_2~-/NO_3~-浓度升高,基底动脉直径增大(P＜0.05).结论 浅低温16～32 h可缓解蛛网膜下腔出血犬脑血管痉挛,且随浅低温时间延长该作用增强,其机制可能与降低全身和脑组织ET-1水平,升高NO水平,调节脑血管收缩-舒张平衡有关.     

Increased Expression and Activity of Hepatic Lipase in the Liver of Morbidly Obese Adult Patients in Relation to Lipid Content

Background  The types and sources of lipid deposition in the liver of most patients with morbid obesity, as well as the effects of bariatric surgery, are discussed. Methods  In 26 patients with morbid obesity who underwent bariatric surgery, we analyzed different kinds of lipids and hepatic lipase (HL) from both plasma and liver biopsies performed 12–18 months after surgery. Results  The HL activity and HL-mRNA in morbidly obese (MO) livers were high (258 ± 17 mU/g, and 4.5-fold, respectively); after surgery, the activity decreased (137 ± 15 mU/g, p < 0.001) but not the levels of HL-mRNA (4.3-fold). Plasma HL activity was also high (4.31 ± 0.94 mU/mL plasma), and it decreased during weight loss (2.01 ± 0.29 mU/mL, p < 0.01); moreover, it correlated (r = 0.3694, p < 0.05) with decreased liver HL activity. Adrenocorticotropic hormone in MO was higher (27 ± 3 pg/mL) than after surgery (13 ± 1 pg/mL, p < 0.001). All hepatic and plasma lipids were significantly increased in MO patients, but, after bariatric surgery, most of those parameters recovered or normalized. Liver HL activity correlated with total and esterified cholesterol (r = 0.4399, p < 0.001 and r = 0.4395, p < 0.01, respectively). Conclusion  High HL in MO patients could allow for liver intake of cholesterol that could be re-exported to steroidogenic organs to synthesize steroidal hormones. A decrease of plasma HL during weight loss could be a good index for improvement of liver disease.     

Improvement of Associated Respiratory Problems in Morbidly Obese Patients after Open Roux-en-Y Gastric Bypass

Background Obstructive sleep apnea syndrome (OSAS) is present in 44% of patients scheduled for bariatric surgery. Respiratory dysfunction associated with this syndrome is attributable to chronic obstructive pulmonary disease (COPD) and/or obesity hypoventilation syndrome (OHS).We studied the long-term effect of bariatric surgery on weight loss, on the respiratory comorbidities associated with obesity, and on the need for non-invasive positive pressure ventilation. Methods We followed a sample of patients with respiratory co-morbidity scheduled for open Capella Roux-en-Y gastric bypass (RYGBP) over 5-years. Patients who were positive for polysomnographic studies and required continous positive airway pressure (CPAP) before surgery were included. All patients were subjected to the same anesthetic and surgical protocols. At 1 year after surgery, polysomnographic studies were performed and arterial blood gases and pulmonary function were tested. Results Of the 209 patients scheduled for bariatric surgery during the study period, 105 had respiratory co-morbidity. Of these, 30 required CPAP-BiPAP treatment before surgery and were included in our study. Surgery took 128 minutes (range 70 to 210 minutes). Tracheal extubation in the operating theater was possible for 26 patients (86.7%). During the early postoperative period, 7 patients (23.3%) presented respiratory complications. Length of hospitalization was 6.87 days (range 4 to 11 days). At 1 year after RYGBP, patients presented significant weight loss and improvement of hypoxemia (from 73.3 ± 10.6 to 90.5 ± 11.5, P = 0.000), hypercarbia (from 44.5 ± 5.7 to 40.6 ± 4.9, P = 0.005), and in spirometric (P = 0.004) and polysomnographic results (P = 0.001). CPAP-BiPAP treatment after weight loss was necessary in only 14% of patients (P = 0.001). Conclusions Weight loss after RYGBP improved arterial blood gases, respiratory tests and polysomnographic studies. CPAP treatment can be withdrawn in most patients.     

Endothelin-1 in plasma, cisternal CSF and microdialysate following aneurysmal SAH

Summary Objective. Endothelin-1 (ET-1) is postulated to play an important role in the development of cerebral vasospasm (CVS) following SAH. This study was conducted to investigate the time course of ET-release in three different sources: CSF, plasma and microdialysate. Methods. In a prospective study ET-1-concentrations were measured in plasma, cisternal CSF and microdialysate in 20 patients with aneurysmal SAH for at least 8 days after hemorrhage. Results. ET-1 concentration in microdialysate was almost four times higher compared to CSF and plasma. (p<0.001) Only in CSF ET-1-release showed a significant increase over time with highest values on day 5 post ictus (p = 0.03). This was parallel to the increase of transcranial Doppler velocities. ET-1 in plasma and microdialysate did not change over time. Conclusion. ET-1 may have a different biological function in different biological tissues. Only ET-1 in CSF seemed to be associated with CVS. An erratum to this article is available at .     

Urinary transforming growth factor beta-1 as a marker of renal dysfunction in sickle cell disease

Renal dysfunction affects 5–18% of patients with sickle cell disease (SCD). To date, no studies have described urinary levels of transforming growth factor β-1 (TGF-β1), a marker of fibrosis, and neutrophil gelatinase-associated lipocalin (NGAL), a marker of acute/chronic kidney disease, as biomarkers in identifying patients at risk of developing renal disease in SCD. We hypothesized that SCD subjects will have increased urinary excretion of TGF-β1 and NGAL compared with healthy controls (CTR). We examined 51 SCD subjects: 42 HbSS, 8 HbSC, and 1 HbSD. Sixteen out of 42 patients with HbSS were on hydroxyurea (HU). Urinary excretion of TGF-β1 was 26.4 ± 1.5 pg/mgCr in SCD subjects vs 15.0 ± 2.4 pg/mgCr in CTR (p < 0.00001). SCD patients with hemoglobin < 9 g/dl had higher urinary TGF-β1 than patients with milder anemia (p = 0.002). Urinary TGF-β1 trended lower in HbSS patients treated with HU (23.61 ± 2.6 pg/mgCr), vs patients not on HU (27.69 ± 1.8 pg/mgCr; p = 0.055). There was no correlation between urinary TGF-β1 and microalbuminuria or estimated glomerular function. There was no difference in urinary NGAL in SCD patients vs CTR. We suggest that urinary TGF-β1 may serve as a marker of early renal injury in SCD.     

Lipoprotein Lipase but Not Hormone-Sensitive Lipase Activities Achieve Normality After Surgically Induced Weight Loss in Morbidly Obese Patients

Background  Although bariatric surgery is currently the most common practice for inducing weight loss in morbidly obese patients (BMI > 40 kg/m²), its effect on the lipid content of adipose tissue and its lipases (lipoprotein lipase [LPL] and hormone-sensitive lipase [HSL]) are controversial. Methods  We analyzed LPL and HSL activities and lipid content from plasma as well as subcutaneous (SAT) and visceral (VAT) adipose tissue of 34 morbidly obese patients (MO) before and after (6 and 12 months) Roux-en-Y gastric bypass surgery and compare the values with those of normal weight (control) patients. Results  LPL activity was significantly higher in MO (SAT = 32.9 ± 1.0 vs VAT = 36.4 ± 3.3 mU/g tissue; p < 0.001) than in control subjects (SAT = 8.2 ± 1.4 vs VAT = 6.8 ± 1.0 mU/g tissue) in both adipose depots. HSL activity had similar values in both types of tissue (SAT = 32.8 ± 1.6 and VAT = 32.9 ± 1.6 mU/g) of MO. In the control group, we found similar results but with lower values (SAT = 11.9 ± 1.4 vs VAT = 12.1 ± 1.4 mU/g tissue). Twelve months after surgery, SAT LPL activity diminished (9.8 ± 1.4 mU/g tissue, p < 0.001 vs morbidly obese), while HSL (46.6 ± 3.7 mU/g tissue) remained high. All lipids in tissue and plasma diminished after bariatric surgery except plasma nonesterified fatty acids, which maintained higher levels than controls (16 ± 3 vs 9 ± 0 mg/dL; p < 0.001, respectively). Conclusions  When obese patients lose weight, they lose not only part of the lipid content of the cells but also the capacity to store triacylglycerides in SAT depots. E. Pardina and A. Lecube contributed equally to this study. J.A. Baena-Fustegueras and J. Peinado-Onsurbe share senior authorship.     

Effect of raloxifene after recombinant teriparatide [hPTH(1–34)] treatment in postmenopausal women with osteoporosis

Summary Loss of bone mineral density occurs after discontinuation of teriparatide, if no subsequent treatment is given. Sequential raloxifene prevented rapid bone loss at lumbar spine and further increased bone mineral density (BMD) at femoral neck, whether raloxifene was started immediately or after a one-year delay following teriparatide treatment. Introduction We compared the sequential effects of raloxifene treatment with a placebo on teriparatide-induced increases in bone mineral density (BMD). A year of open-label raloxifene extended the study to assess the response with and without delay after discontinuation of teriparatide. Methods Following a year of open-label teriparatide 20 μg/day treatment, postmenopausal women with osteoporosis were randomly assigned to raloxifene 60 mg/day (n = 157) or a placebo (n = 172) for year 2, followed by a year of open-label raloxifene. BMD was measured by dual energy x-ray absorptiometry. Results The raloxifene and placebo groups showed a decrease in lumbar spine (LS) BMD in year 2 for raloxifene and placebo groups (−1.0 ± 0.3%, P = 0.004; and −4.0 ± 0.3%, P < 0.001, respectively); the decrease was less with raloxifene (P < 0.001). Open-label raloxifene treatment reversed the LS BMD decrease with a placebo, resulting in similar decreases 2 years after randomization (−2.6 ± 0.4% (raloxifene-raloxifene) and −2.7 ± 0.4% (placebo-placebo). At study end, LS and femoral neck (FN) BMD were higher than pre-teriparatide levels, with no significant differences between the raloxifene-raloxifene and placebo-raloxifene groups, respectively (LS: 6.1 ± 0.5% vs. 5.1 ± 0.5%; FN: 3.4 ± 0.6% vs. 3.0 ± 0.5%). Conclusion Sequential raloxifene prevented rapid bone loss at the LS and increased FN BMD whether raloxifene was started immediately or after a one-year delay following teriparatide treatment. Preliminary data presented previously at the International Osteoporosis Foundation World Congress on Osteoporosis, Toronto Canada June 2–6, 2006, abstract published: Adami S, Munoz-Torres M, Econs MJ, Sipos A, Xie L, Dalsky GP, McClung M, Felsenberg D, Brown JP, Brandi ML, San Martin J. Effect of raloxifene after teriparatide treatment in postmenopausal women with osteoporosis. Osteoporos Int. 2006;17(Suppl 2):S137.     

Caldesmon expression is decreased in women with anterior vaginal wall prolapse: a pilot study

Introduction and hypothesis  The purpose of this study is to compare vaginal caldesmon expression in women with and without anterior vaginal wall prolapse. Methods  Vaginal tissues were sampled in women with (n = 11) or without (n = 11) vaginal wall prolapse. Caldesmon messenger RNA (mRNA) expression was assessed by quantitative real-time polymerase chain reaction. Immunohistochemistry and digital image analysis were used to determine caldesmon protein expression in the histologic sections. Results  There were no significant differences in demographic data between the two groups. Caldesmon mRNA expression was significantly decreased in the vaginal tissue from women with anterior vaginal wall prolapse compared to women without prolapse [(caldesmon mean ± SD mRNA expression in relative units) 0.03 ± 0.03 vs 0.17 ± 0.17, P = 0.02]. The fractional area of nonvascular caldesmon staining in the vagina of women with anterior vaginal wall prolapse was significantly decreased compared to women without prolapse [mean ± SD (0.09 ± 0.04 vs 0.16 ± 0.09, P = 0.03)]. Conclusions  Vaginal caldesmon expression is significantly decreased in women with anterior vaginal wall prolapse compared to normal subjects.     

Predicting Maximum Roux-en-Y Gastric Bypass-Induced Weight Reduction — Preoperative Plasma Leptin or Body Weight?

Background Weight loss after bariatric surgery varies between patients, and predicting the extent thereof is often inaccurate. The aim of this study was to assess the potential of preoperative plasma leptin and body weight in predicting the maximum weight loss within 2 years after Roux-en-Y gastric bypass (RYGBP). Methods The study comprised 68 subjects (39 women, 29 men; mean age 36.4 ± 10.2 years, body weight 130.3 ± 24.8 kg, BMI 44.4 ± 6.8 kg/m²) undergoing RYGBP who were followed for 2 years. Baseline and maximum follow-up plasma leptin and weight were assessed. Results Mean maximum weight reduction of 50.5 ± 19.1 kg (38.0 ± 9.0%, range 24 – 100 kg) was noted at 15 ± 4 months after RYGBP. Baseline plasma leptin was 37.9 ± 14.5 ng/ml, and decreased to 17.4 ± 8.1 ng/ml (P < 0.001) at maximum weight reduction. No significant correlation between baseline plasma leptin and absolute or relative weight reduction or minimum body weight achieved was noted. No significant plasma leptin threshold which would be predictive for any consistent extent of weight loss was found. However, baseline body weight was a strong determinant of minimum body weight attained (r = 0.67; P < 0.01) and of maximum absolute weight reduction (r = 0.81; P < 0.01). Conclusion Preoperative plasma leptin concentration cannot be used as a predictor of weight reduction following RYGBP. Preoperative body weight is a reliable predictor of post-RYGBP weight loss.     

Changes in Resting Energy Expenditure and Body Composition after Weight Loss following Roux-en-Y Gastric Bypass

Background The objective of this study was to evaluate changes in resting energy expenditure (REE), body composition and metabolic parameters, and to investigate predictors of the results in seriously obese patients after Roux-en-Y gastric bypass (RYGBP). Methods 31 patients (BMI 44.4 ± 4.8 kg/m2; 27 female, 4 male; 37.3 ± 11.1 y) were evaluated at baseline and 6 months after RYGBP. Weight, REE, waist circumference (WC), fat mass (FM) and fat-free mass (FFM), physical activity, food intake, fasting glucose (GLU), insulin (INS), HOMA-IR and lipid concentrations were measured. Results At 6 months, percentage of weight loss (%WL) was 29.0 ± 4.4% and percentage of excess weight loss was (%EWL) 59.7 ± 12.3%. FM loss corresponded to 77.1 ± 12.2% of the weight loss. REE decreased from 33.4 ± 4.1 to 30.1 ± 2.6 kcal/kg FFM (P < 0.05). Significant decreases (P < 0.001) were observed in GLU, INS, HOMA-IR, LDL-cholesterol and triglycerides. %EWL was correlated with baseline INS (r = 0.44; P = 0.014), baseline HOMA (r = 0.43; P = 0.017), change in %FM (r = 0.67; P < 0.001) and change in WC (r = 0.5; P < 0.01). Decrease in REE/FFM (%) was positively correlated with baseline REE/FFM% (r = 0.51; P < 0.005) and change in %FM (r = 0.69; P < 0.001). Initial REE/FFM, baseline energy balance and FM change explain 90% of REE/FFM decrease. Conclusion RYGBP was an effective procedure to induce significant weight loss, fat mass loss and improvement in metabolic parameters in the short term. Metabolic adaptation was not related to FFM wasting but to a higher baseline REE. Fasting hyperinsulinemia was the best single predictor of weight loss after RYGBP. Supported by a grant from University of Chile (DID–SAL 01/04–2).     

Increase of Bone Resorption and the Parathyroid Hormone in Postmenopausal Women in the Long-term after Roux-en-Y Gastric Bypass

Background  The effects of Roux-en-Y Gastric Bypass (RYGB) on bone in the long-term remains unclear. We assessed bone metabolism and bone mineral density (BMD) 1 to 5 years after RYGB. Methods  We designed a retrospective cohort study in 26 postmenopausal women (58.0 ± 3.9 years old) with RYGB 3.5 ± 1.1 years before (body mass index (BMI) 29.5 ± 3.8 kg/m², presurgery 43.6 ± 5.5 kg/m²) and 26 nonoperated women (57.5 ± 4.7 years old, BMI 29.2 ± 4.1 kg/m²) matched by age and BMI. The main measures were BMD, serum carboxy telopeptide (CTx), total alkaline phosphatases (ALP), parathyroid hormone (PTH), 25-hydroxyvitamin D (25OHD), and ghrelin. Results  RYGB group, compared to nonoperated women, had higher CTx (0.71 ± 0.21 vs. 0.43 ± 0.15 ng/ml; P < 0.01) and PTH (68.3 ± 35 vs. 49.4 ± 16 pg/ml; P = 0.02). There were no differences between RYGB and nonoperated women in: calcium and vitamin D intake (759 ± 457 vs. 705 ± 460 mg/day; 176 ± 160 vs. 111 ± 86 UI/day), ghrelin (763 ± 336 vs. 621 ± 274 pg/ml), ALP (101 ± 22 vs. 94 ± 25 UI/l), 25OHD (18.8  ± 7.6 vs. 17.4 ± 5.9 ng/ml), lumbar spine BMD (1.059 ± 0.32 vs. 1.071 ± 0.207 g/cm²), or femoral neck BMD (0.892 ± 0.109 vs. 0.934 ± 1.1 g/cm²). Conclusions  RYGB is associated to high bone resorption and hyperparathyroidism prevalence in postmenopausal women in the long-term. This occurs independently of the intake of calcium, vitamin D status, or ghrelin and does not seem to affect BMD after RYGB.     

[D-Val22]big ET-1[16–38] inhibits endothelin-converting enzyme activity: a promising concept in the prevention of cerebral vasospasm

The aim of this study was to investigate whether the blocking of endothelin-converting enzyme (ECE) activity offers a new approach to inhibiting the development of cerebral vasospasm after subarachnoid hemorrhage (SAH) by preventing transformation of big endothelin-1 (big ET-1) to vasoactive endothelin-1 (ET-1). The effect of potential ECE inhibitors was determined in vitro by measurement of isometric contractions, induced by big ET-1, in isolated rat basilar arteries. Intact and de-endothelialized endothelium (E+ and E-, respectively) segments were examined after preincubation with the putative ECE inhibitors: phosphoramidon (10^–4 M), and [²²D-Val]big ET-1[16–38] (10^–5 M and 10^–6 M). Additionally, the effect of [D-Val²²]big ET-1[16–38] was investigated in rabbits after intracisternal application in order to inhibit the contraction of the basilar artery induced by (2×10^–6 M) big ET-1. Application of 10^–4-M phosphoramidon resulted in a statistically significant decrease in big ET-1-induced contraction in E+ and E- segments; 10^–5-M and 10^–6-M [²²D-Val]big ET-1[16–38] in E- segments produced no statistically significant effect. The application of 10^–6-M [²²D-Val]big ET-1[16–38] in E+ segments caused increased contractions, as shown by the shift to the left of the concentration-effect curve (CEC). In the rabbit group pretreated with [D-Val²²]big ET-1[16–38] (2×10^–5 M) (n=8), the angiographically measured diameter of the basilar artery increased from 0.63±0.12 mm to 0.66±0.12 mm. In the control group (n=8), this diameter decreased from 0.71±0.13 mm to 0.57±0.15 mm. This corresponded to an increase in vessel diameter of 5.24±9.89% in the treatment group and a decrease of 19.54±15.81% in the control group (P=0.002). The present study indicates the existence of functional ECE activity in rat basilar artery, which differs in the endothelium and the smooth muscle layer. These results demonstrate that [D-Val²²]big ET-1[16–38] has a potent ECE-inhibitory effect, preventing cerebral vasospasm in rabbit basilar artery by inhibiting the transformation of big ET-1 to vasoactive ET-1 after intracisternal application in vivo, whereas no inhibitory effect was detectable in rat basilar artery in vitro. Therefore, further studies of the biochemical nature of cerebrovascular ECE activity are required.     

Systemic and cavernous plasma levels of endothelin (1-21) during different penile conditions in healthy males and patients with erectile dysfunction

 The role of the sympathetic adrenergic nerves in mediating the constant tone of penile flaccidity and returning the erect penis to its flaccid state is fairly well established. However, it is not yet known whether additional nonadrenergic transmitters are involved in this process. The peptide endothelin-1 (ET-1) may be one of the factors contributing to such a control. Moreover, it has been speculated by various authors that ET-1 might be involved in the pathophysiology of erectile dysfunction. The present study was undertaken to determine whether or not there is a difference in the courses of ET-1/-2 plasma levels registered in systemic and cavernous blood cavities taken from healthy males and patients with ED during different penile conditions (flaccidity, tumescence/rigidity, detumescence). Thirty-two healthy adult males and 25 patients were exposed to visual and tactile erotic stimuli in order to elicit penile tumescence and, in the group of healthy volunteers, rigidity. Whole blood was aspirated from the corpus cavernosum and the cubital vein, and ET-1/-2 was determined in plasma aliquots by means of an enzyme-linked immunoassay (ELISA). Mean systemic and cavernous plasma level of ET-1/-2 in blood samples obtained from the volunteers was 0.2–0.7 fmol/ml. In the healthy males, no changes in ET-1/-2 levels were observed in the systemic and cavernous blood during penile tumescence, rigidity and detumescence. In the group of patients, mean plasma ET-1/-2 levels in the phase of penile flaccidity and detumescence were found to be higher in the systemic circulation than in the cavernous blood (flaccidity: 0.52 ± 0.38 fmol/ml vs. 0.48 ± 0.46 fmol/ml, respectively; detumescence: 0.53 ± 0.33 fmol/ml vs. 0.27 ± 0.11 fmol/ml, respectively). No differences in the plasma courses of ET-1/-2 were found between patients with an organogenic and psychogenic etiology of ED. In the phase of detumescence, the mean ET-1/-2 level was lower in the cavernous blood cavities taken from the patients than in the samples obtained from the healthy males. Our study revealed a difference in the profiles of ET-1/-2 registered in the cavernous blood of healthy subjects and patients with erectile dysfunction. Nevertheless, since this difference seems to be of no physiological significance, our data counteract the hypothesis of an ultimate importance of ET-1 in the control of penile flaccidity and detumescence and do not support speculations regarding an involvement of ET-1 in the pathophysiology of erectile dysfunction.     

Gastric/Intestinal Electrical Stimulation Modulates Appetite Regulatory Peptide Hormones in the Stomach and Duodenum in Rats

Background Gastric/intestinal electrical stimulation (GIES) has been used to suppress appetite in the treatment of obesity with promising results. However, the mechanisms by which GIES benefits obese patients are not completely understood. This study investigated the acute effects of GIES on gastric and intestinal tissue levels of peptide hormones related to satiety and appetite in rats. Methods 32 rats were divided into 4 groups: 1) sham stimulation, 2) gastric electrical stimulation (GES) with pulse trains, 3) GES with long pulse, and 4) duodenal electrical stimulation (DES) with pulse trains. After 2 hours of GIES, the rats were sacrificed immediately, and gastric fundus, duodenum and distal colon were harvested and extracted. Hormone levels of ghrelin, obestatin, cholecystokinin-8 (CCK-8) and peptide YY (PYY) were measured by radioimmunoassay (RIA). Results 1) The mean gastric fundus ghrelin level was 1789.04 ± 362.81 pg/mg in the sham stimulation and significantly decreased with GES of pulse trains (597.85 ± 195.33 pg/mg, P = 0.012), GES of long pulse (754.6 ± 282.6 pg/mg, P = 0.039) and DES (731.69 ± 110.84pg/mg, P = 0.037). 2) The mean duodenal CCK-8 concentration was 413.27 ± 42.14 pg/mg in the sham stimulation and significantly increased by DES (762.6 ± 98.75 pg/mg, P = 0.013) but not in others. 3) Neither gastric obestatin nor distal colonic PYY was altered by any of GES or DES. Conclusions GIES significantly impacts appetiterelated peptide hormones in gastric and duodenal tissues. Acute GIES-induced manipulation of gut peptide hormones related to appetite and satiety is a nonpharmacologic, well-tolerated clinical procedure that could substantially contribute to the successful treatment and long-term management of obesity.     

Relation Between Thyroid Hormones and Insulin Resistance in Hemodialysis Patients

Insulin resistance (IR) is a common problem in patients with ESRD on regular HD, and it is related to many complications, including cardiovascular complications, the major killer in these patients. Disorders of thyroid function are common in patients with ESRD. Many factors have been claimed to contribute to IR in HD patients. Our aim is to study the relations between thyroid hormones and IR in HD patients for better understanding and management of IR. The study involved 35 patients with ESRD under regular HD (group 1) and 20 normal control subjects (group 2). All of them underwent complete history taking and clinical examination: biochemical and hematological, thyroid hormones TSH, free T3 (FT3) and free T4 (FT4), and insulin resistance using the homeostasis model assessment (HOMA-IR). Patients with DM and those with known thyroid disorders were excluded from the study. Comparing HD patients and normal control subjects shows significant differences as regards FT3 (p = 0.04) 33.58 ± 12.14 vs. 40.63 ± 11.27 pg/l, respectively; TSH (p = 0.03) 3.29 ± 3.83 vs. 1.80 ± 0.88 mu/l, respectively; fasting insulin level (p < 0.001) 30.1 ± 6.05 vs. 10.68 ± 2.77 mu/ml, respectively; HOMA (p < 0.001) 6.72 ± 1.41 vs. 2.4 ± 0.67, respectively. There is no significant difference as regards FT4 (p = 0.36) 15.17 ± 6.72 vs. 16.35 ± 2.66 pmol/l, respectively. Bivariate correlation in HD patients shows HOMA IR correlates with FT3 (p < 0.001), FT4 (p < 0.001), TSH (p < 0.001), HDL (p < 0.001), and hematocrit (p < 0.001). No correlations were found with BMI, age, total cholesterol, LDL, or triglycerides. Linear regression analysis showed HOMA-IR was independently determined by HDL (p = 0.04), hematocrit (p = 0.02), and TSH (p = 0.008). IR is very common in HD patients. There is a close correlation between IR and thyroid hormones. TSH, HDL, and hematocrit levels independently determine IR. Regular follow-up of these factors is necessary for proper management of IR.     

Intracisternal infusion of magnesium sulfate solution improved reduced cerebral blood flow induced by experimental subarachnoid hemorrhage in the rat

Magnesium has neuroprotective and antivasospastic properties in the presence of subarachnoid hemorrhage (SAH). The present study investigated the effect of intracisternal administration of magnesium on cerebral vasospasm in the experimental SAH rat model. The rat double-SAH model (0.2 mL autologous blood injected twice into the cisterna magna) was used. Normal saline (SAH group, N = 8) or 10 mmol/L magnesium sulfate in normal saline (SAH + MG group, N = 8) was infused into the cisterna magna at 1.5 μL/min for 30 min on day 5. Control rats without SAH also received intracisternal infusion of normal saline (control group, N = 6). Local cerebral blood flow (CBF) at 24 locations and the weighted average were quantitatively measured by the autoradiographic technique using [¹⁴C]iodoantipyrine during infusion. The weighted average CBF was significantly reduced (P < 0.01, Student’s t-test) in the SAH group (0.78 ± 0.16 mL g⁻¹ min⁻¹) compared to the control group (1.0 ± 0.15 mL g⁻¹ min⁻¹) and was significantly improved (P < 0.01, Student’s t-test) in the SAH + MG group (0.98 ± 0.18 mL g⁻¹ min⁻¹). Local CBF was significantly reduced (P < 0.05, unpaired t test) in 16 locations in the SAH group and significantly improved (P < 0.05, unpaired t test) in 12 locations in the SAH + MG group. Intracisternal infusion of magnesium sulfate significantly improved reduced CBF induced by experimental SAH in the rat.