Xamoterol in patients with dilated cardiomyopathy: an increase in beta-receptors in lymphocytes

Xamoterol, a partial-beta 1 agonist, was administered orally (100 mg, twice daily) to healthy volunteers (n = 8) and to patients with heart failure (n = 8) for one week. The density (Bmax) and affinity (Kd) of lymphocyte beta-receptors were lower in the patients with heart failure than in the healthy volunteers (Bmax = 931 +/- 214 vs 1466 +/- 373 sites/cell, and Kd = 0.60 +/- 0.11 vs 1.07 +/- 0.14 nM). During treatment with xamoterol, Bmax (7169 +/- 3768 and 7749 +/- 3807 sites/cell) and Kd (6.01 +/- 3.84 and 9.06 +/- 4.66 nM) increased strikingly (p less than 0.01) in both groups. For 12 months, xamoterol (100 mg bd) was given in the same manner to 10 patients with dilated cardiomyopathy. The long-term effects after three and 12 months were assessed. Xamoterol reduced the cardiothoracic ratio from 57 +/- 6% to 55 +/- 5% after three months and 54 +/- 5% after 12 months of treatment (both p less than 0.05), and increased exercise tolerance from 5 +/- 2 min to 7 +/- 2 min and to 7 +/- 2 min (p less than 0.01, p less than 0.05). Echocardiographic fractional shortening increased from 13 +/- 6% to 20 +/- 8% (p less than 0.01) and to 20 +/- 10% (p less than 0.05). Pulmonary wedge pressure during exercise at the same work load decreased from 40 +/- 12 mmHg to 25 +/- 9 mmHg (p less than 0.01) in three months; whereas pulmonary wedge pressures during exercise or at rest in 12 months were unchanged. Exercise heart rate decreased from 118 +/- 9 beats/min to 106 +/- 6 beats/min in three months (p less than 0.01), but was unchanged in 12 months. Bmax and Kd of the beta-receptors increased from 1024 +/- 413 sites/cell and 0.67 +/- 0.27 nM to 1976 +/- 497 sites/cell and 1.60 +/- 0.42 nM (both p less than 0.01), respectively, in three months, and 1584 +/- 650 sites/cell (NS) and 1.21 +/- 0.54 nM (p less than 0.05), respectively, in 12 months. It is concluded that xamoterol improves exercise tolerance, hemodynamics and resolves subjective symptoms for certain patients with dilated cardiomyopathy by its actions as a beta-agonist and beta-antagonist during longterm treatment.     

Effect of Mongolian plants on in vivo insulin action in diabetic rats

In the present study, we firstly performed a preliminary investigation on the acute effect of Mongolian medicinal plant extracts (Dryopteris species, Aspidiaceae) on the glucose tolerance in rats, evaluated by an oral glucose tolerance test (OGTT). Then, we investigated the effect of the same extracts on in vivo insulin action in streptozotocin (50 mg kg(-1) BW, i.v.)-induced diabetic rats by means of the euglycemic clamp. In diabetic rats, the glucose metabolic clearance rate (MCR) during 3.0 (low-dose) and 30.0 mU kg(-1)min(-1) (high-dose) insulin infusion was significantly higher in animals administered with plant extracts (500 mg kg(-1) BW, p.o.), compared with saline-administered animals (low-dose--normal control: 16.3+/-0.7 ml kg(-1)min(-1) versus plant extract 1: 15.8+/-0.6 ml kg(-1)min(-1) and plant extract 2: 14.0+/-0.5 ml kg(-1)min(-1), diabetic control: 10.9+/-0.6 ml kg(-1)min(-1) versus plant extract 1: 19.3+/-1.4 ml kg(-1)min(-1) and plant extract 2: 20.5+/-1.5 ml kg(-1)min(-1); high-dose-normal control: 50.9+/-2.6 ml kg(-1)min(-1) versus plant extract 1: 49.8+/-2.6 ml kg(-1)min(-1) and plant extract 2: 48.4+/-2.4 ml kg(-1)min(-1), diabetic control: 26.9+/-1.6 ml kg(-1)min(-1) versus plant extract 1: 33.5+/-1.7 ml kg(-1)min(-1) and plant extract 2: 37.2+/-1.9 ml kg(-1)min(-1); P<0.05, respectively). These results suggest that a single administration of the two Mongolian plant extracts can improve glucose utilization and insulin resistance in diabetic rats.     

Early changes in ventricular function in diastolic phase in the resting coronary patient

The aim of this study is to test left ventricular diastolic function in coronary artery disease patients with preserved systolic performance. Two groups of patients (25 coronary artery disease patients with angiographic proved coronary artery stenosis, but with normal hemodynamic and angiographic indices of systolic phase, first group; and 14 normal subjects for control, second group) were tested comparing their systolic and diastolic ventricular function indices, obtained by using a Millar microtip catheter and a computerized program. Systolic ventricular function was similar in the two groups (EF: 0.61 +/- 0.05 vs 0.62 +/- 0.03, p: n.s.; Vmax:120 +/- 28 vs 112 +/- 24 sec-1, p: n.s.), while diastolic indices were significantly different (lowest diastolic pressure: 3.7 +/- 2.4 vs -1.72 +/- 1.45 mmHg, p less than 0.01; end-diastolic pressure: 11.2 +/- 4.2 vs 6.5 +/- 2.8 mmHg, p less than 0.05; T constant: 45 +/- 8 vs 35 +/- 6 mmHg, p less than 0.001; end-diastolic compliance: 2.79 +/- 0.3 X 10(-2) vs 5.68 +/- 0.4 X 10(-2) mmHg-1, p less than 0.001; Kp: 0.041 +/- 0.006 vs 0.003 +/- 0.004 p less than 0.001). In conclusion, impairment of left ventricular diastolic phase may be one of the earliest manifestations of functional alterations of ischemic ventricle.     

Adrenocorticotropin-induced changes in ovine pituitary gonadotropin secretion in vitro

In vitro pituitary perifusion experiments were conducted to examine the effect of ACTH and related peptides on basal and GnRH-stimulated gonadotropin release. Treatments of 5 X 10(-7) M ACTH-(1-39), ACTH-(1-24), or ACTH-(18-39) were examined for their ability to influence basal gonadotropin secretion and the subsequent response to a 10(-9)- or 10(-8) M GnRH challenge. Administration of the 1-39 or 18-39 peptide sequences of ACTH similarly stimulated the release of LH and FSH (P less than 0.01). ACTH-(1-24) had no effect on basal gonadotropin secretion. Pretreatment with ACTH-(1-39) inhibited the LH and FSH responses to 10(-9) and 10(-8) M GnRH (P less than 0.05). Suppression of the LH response to 10(-8) M GnRH (P less than 0.05) and the FSH response to 10(-9) M GnRH (P less than 0.05) was observed after ACTH-(1-24) treatment. The administration of ACTH-(18-39) had no significant effect on GnRH-induced gonadotropin release. PRL concentrations were not affected by any of the ACTH peptides. Exposure to 10(-10) M GnRH or 5 X 10(-7) M synthetic ACTH-(1-39) produced an equivalent stimulation of LH secretion. GnRH pretreatment enhanced (P less than 0.05), while ACTH-(1-39) diminished (P less than 0.05), the subsequent response to GnRH. The GnRH receptor antagonist [D-pGlu1, D-Phe2, D-Trp3,6]GnRH attenuated the LH and FSH responses to GnRH and ACTH-(1-39) (P less than 0.05). The results obtained in this study indicate that certain portions of the ACTH molecule may affect gonadotropin secretion, perhaps by interacting with the GnRH receptor.     

Age-related differences in metabolic adaptations following resistance training in women

The purpose of this study was to determine whether aging alters changes in resting metabolic rate, body composition and insulin sensitivity in response to resistance training (RT) in women. The impact of a 6-month controlled RT program on fat-free mass (FFM), resting energy expenditure (REE), and glucose disposal was examined in 19 younger (27.8+/-3.5 yr; range 18-35) and 12 older (66.6+/-4.9 yr, range 55-70) non-obese caucasian women. For younger women, the RT program increased body weight (59.1+/-6.2 to 60.8+/-6.1 kg, p<0.05) due to an increase in FFM (39.2+/-3.7-40.4+/-3.2 kg, p<0.05). REE increased from 1379+/-114 to 1451+/-140 kcal day(-1), p<0.0001), and glucose disposal (from 364.1+/-91.1 to 402.1+/-87.8 mg min(-1), p<0.05). Neither fat mass nor VO2max changed significantly. On the other hand, older women lost fat mass (24.0+/-4.6-23.2+/-5.4 kg, p<0.05) and tended to gain FFM (from 37.3+/-4.0-38.0+/-4.3 kg, +1.9%; p=0.057), whereas no change occurred in body weight, REE, VO(2)max or glucose disposal. Thus, younger women showed greater metabolic changes in body composition, REE and insulin sensitivity in response to RT than older women. These results suggest an age-related alteration in metabolic changes in response to a 6-month RT program in previously untrained women.     

Role of nitric oxide-cGMP pathway in adrenomedullin-induced vasodilation in the rat

We previously reported that adrenomedullin (AM), a potent vasodilator peptide discovered in pheochromocytoma cells, stimulates nitric oxide (NO) release in the rat kidney. To further investigate whether the NO-cGMP pathway is involved in the mechanisms of AM-induced vasodilation, we examined the effects of E-4021, a cGMP-specific phosphodiesterase inhibitor, on AM-induced vasorelaxation in aortic rings and perfused kidneys isolated from Wistar rats. We also measured NO release from the kidneys using a chemiluminescence assay. AM (10(-10) to 10(-7) mol/L) relaxed the aorta precontracted with phenylephrine in a dose-dependent manner. Denudation of endothelium (E) attenuated the vasodilatory action of AM (10(-7) mol/L AM: intact (E+) -25.7+/-5.2% versus denuded (E-) -7. 8+/-0.6%, P<0.05). On the other hand, pretreatment with 10(-8) mol/L E-4021 augmented AM-induced vasorelaxation in the intact aorta (-49. 0+/-7.9%, P<0.05) but not in the denuded one. E-4021 also enhanced acetylcholine (ACh)-induced vasorelaxation in the rat intact aorta (10(-7) mol/L ACh -36.6+/-8.4% versus 10(-8) mol/L E-4021+10(-7) mol/L ACh -62.7+/-3.1%, P<0.05). In perfused kidneys, AM-induced vasorelaxation was also augmented by preincubation with E-4021 (10(-9) mol/L AM -15.4+/-0.6% versus 10(-8) mol/L E-4021+10(-9) mol/L AM -23.6+/-1.2%, P<0.01). AM significantly increased NO release from rat kidneys (DeltaNO: +11.3+/-0.8 fmol. min-1. g-1 kidney at 10(-9) mol/L AM), which was not affected by E-4021. E-4021 enhanced ACh-induced vasorelaxation (10(-9) mol/L ACh -9.7+/-1.7% versus 10(-8) mol/L E-4021+10(-9) mol/L ACh -18.8+/-2.9%, P<0.01) but did not affect ACh-induced NO release from the kidneys. In the aorta and the kidney, 10(-4) mol/L of NG-nitro-L-arginine methyl ester, an NO synthase inhibitor, and 10(-5) mol/L of methylene blue, a guanylate cyclase inhibitor, reduced the vasodilatory effect of AM. These results suggest that the NO-cGMP pathway is involved in the mechanism of AM-induced vasorelaxation, at least in the rat aorta and kidney.     

Altered vascular injury responses in mice deficient in protease-activated receptor-1

Expression of protease-activated receptor-1 (PAR-1), a cell-surface receptor for thrombin, is increased in balloon-injured rat carotid artery and human atherosclerotic tissue. To examine the role of PAR-1 in vascular injury, we compared vascular injury responses in wild-type (WT) and PAR-1-deficient (PAR-1(-/-)) mice. Arterial injury was induced by inserting a flexible guidewire into the common carotid artery and withdrawing it 6 times with rotation. Bromodeoxyuridine, delivered subcutaneously by osmotic minipump, was used to measure cellular proliferation. Mice were perfusion-fixed at 1, 2, 5, 10, and 14 days after injury. Extensive endothelial damage, mural thrombosis, platelet adherence, and medial smooth muscle cell loss and necrosis were apparent at day 1 in both WT and PAR-1(-/-) mice. The incidence of thrombosis or platelet deposition in WT and PAR-1(-/-) mice declined from 100% at day 1 to 25% and 21%, respectively, at 14 days. Endothelial disruption, as assessed by Evan's blue uptake, was maximum at day 1 and declined by day 14. This apparent endothelial regrowth was similar in WT and PAR-1(-/-) mice. Significant medial thickening at 14 days after injury was similar in WT (from 22.8+/-1.7 to 30.7+/-1.9 microm) and PAR-1(-/-) (from 23.2+/-2.1 to 30.5+/-2.2 microm) mice. Medial area also increased in response to injury but to a lesser extent in PAR-1(-/-) mice (from 0.0250+/-0.0044 to 0.0312+/-0.0047 mm(2)) than in WT mice (from 0.0266+/-0.0040 to 0.0398+/-0.0050 mm(2)). Neointima was variable and occurred in 6 of 13 WT and 5 of 12 PAR-1(-/-) mice. However, intimal area tended to be less in PAR-1(-/-) mice (0. 0016+/-0.0007 mm(2)) compared with WT mice (0.0082+/-0.0032 mm(2)), although this difference did not achieve statistical significance (P=0.06). Cell density was significantly greater in normal carotids from PAR-1(-/-) (6.4+/-0.5 x 10(3)/mm(2)) compared with WT (4.3+/-0. 8 x 10(3)/mm(2)) mice and remained elevated after injury. Vessel and lumen diameters tended to increase in WT mice after injury, whereas vessel diameter was unchanged and lumen diameter actually decreased in PAR-1(-/-) mice. Cell proliferation in injured carotid arteries was similar in PAR-1(-/-) and WT mice. These data suggest that PAR-1(-/-) may play a role in vascular injury responses in this mouse model via possible effects on extracellular matrix regulation.     

Pannexins in ischemia-induced neurodegeneration

Pannexin 1 (Px1, Panx1) and pannexin 2 (Px2, Panx2) form large-pore nonselective channels in the plasma membrane of cells and were suggested to play a role in the pathophysiology of cerebral ischemia. To directly test a potential contribution of pannexins in ischemia-related mechanisms, we performed experiments in Px1(-/-), Px2(-/-), and Px1(-/-)Px2(-/-) knockout mice. IL-1β release, channel function in astrocytes, and cortical spreading depolarization were not altered in Px1(-/-)Px2(-/-) mice, indicating that, in contrast to previous concepts, these processes occur normally in the absence of pannexin channels. However, ischemia-induced dye release from cortical neurons was lower, indicating that channel function in Px1(-/-)Px2(-/-) neurons was impaired. Furthermore, Px1(-/-)Px2(-/-) mice had a better functional outcome and smaller infarcts than wild-type mice when subjected to ischemic stroke. In conclusion, our data demonstrate that Px1 and Px2 underlie channel function in neurons and contribute to ischemic brain damage.     

全氟化碳腹腔注射对内毒素肺损伤大鼠中性粒细胞肺浸润的抑制作用

目的通过内毒素(脂多糖,LPS)导致的急性肺损伤(ALI)大鼠模型,探讨全氟化碳(perfluorocarbon,PFC,分子式为 C_8F_(18))腹腔预注射对内毒素导致 ALI 大鼠中性粒细胞(PMN)肺浸润的抑制作用。方法健康雄性 Wistar 大白鼠108只,随机分为正常对照组、PFC 对照组、LPS 组和PFC+LPS 组,每组分别在2、4、6 h 3个时间点各观察9只大鼠。行支气管肺泡灌洗,对支气管肺泡灌洗液(BALF)和血液进行白细胞计数和 PMN 分类,对病理组织进行 PMN 计数,免疫组化检测肺组织E-选择素和胞间黏附分子1(ICAM-1)。结果 (1)LPS 组 BALF 在2、4、6 h 白细胞计数分别为(1.98±0.21)、(2.98±0.43)(3.95±0.29)×10~6/L,PMN 分类分别为0.170±0.069、0.250±0.046、0.351±0.054,均较正常对照组升高[白细胞计数分别为(1.27±0.20)、(1.27±0.18)、(1.26±0.11)×10~6/L,PMN 分类分别为0.041±0.008、0.041±0.007、0.041±0.007,t 值为5.680～18.924,P 均<0.01],而 PFC+LPS 白细胞计数[(1.45±0.39)、(2.67±0.44)、(3.29±0.45)×10~6/L]、PNM分类(0.065±0.024、0.102±0.033、0.174±0.049)显著低于 LPS 组(t 值为-4.224～12.033,P均<0.01)。(2)与之相反,LPS 组血液白细胞计数在4、6 h 表达[(5.26±0.85)、(4.38±0.39)×10~9/L]显著低于正常对照组[(6.29±0.55)、(6.28±0.60)×10~9/L,t 值为-3.088、-7.946,P 均<0.01),而 PFC 预处理后升高。(3)PFC+LPS 组的肺组织 PMN[2、4、6 h 分别为(7.56±1.81)、(18.76±3.51)、(33.99±5.68)个/视野]、E-选择素(积分吸光度值表示,2、4、6 h 分别为867±128、1 161±227、1 922±424)和 ICAM-1(积分吸光度值表示,2、4、6 h 分别为208±78、283±67、625±85)均较 LPS 组[肺组织 PMN 2、4、6 h 分别为(10.78±0.92)、(31.55±3.00)、(54.14±5.49)个/视野,E-选择素2、4、6 h 分别为1 086±256、1 606±408、3 409±1 751,ICAM-12、4、6 h 分别为299±97、378±67、817±149]降低,差异均有统计学意义(t 值为-2.400～-11.480,P 均<0.01)。结论腹腔预注射 PFC 对内毒素导致肺损伤的 PMN 肺浸润有一定的抑制作用,可能与降低肺血管内皮细胞表达E-选择素和 ICAM-1有关。     

Prominent role of P-selectin in the development of advanced atherosclerosis in ApoE-deficient mice

BACKGROUND: Adhesive interactions between leukocytes and endothelial cells are characteristic of the development of atherosclerotic lesions, but the receptors involved remain to be defined. P-selectin is an adhesion receptor expressed on activated endothelial cells or platelets and was shown to be involved in fatty streak formation in LDL receptor-deficient mice on an atherogenic diet. The main purpose of this study is to examine the role of P-selectin in the spontaneous development of advanced atherosclerosis in apoE-deficient mice. METHODDS AND RESULTS: We intercrossed P-selectin-deficient mice with mice lacking apoE and compared lesion development in apoE-deficient mice with P-selectin (apoE(-/-) P(+/+)) and without P-selectin (apoE(-/-) P(-/-)) that were fed normal mouse chow. At 4 months of age, apoE(-/-) P(-/-) mice had 3. 5-fold smaller aortic sinus lesions than apoE(-/-) P(+/+) mice. These were limited to fatty streaks in the apoE(-/-) P(-/-) mice, whereas 70% of apoE(-/-) P(+/+) lesions contained smooth muscle cells. Significantly more of the aortic sinus circumference was covered by lesions in the apoE(-/-) P(+/+) animals. The P-selectin genotype affected macrophage recruitment, because twice as many mononuclear cells were present in the P-selectin-positive lesions. At 15 months, the lesions progressed to the fibrous plaque stage in both genotypes and spread throughout the aorta, but this process was delayed in apoE(-/-) P(-/-) mice. In the aortic sinus, the lesions of the apoE(-/-) P(-/-) mice were 2.6-fold smaller and less calcified. CONCLUSIONS: P-selectin appears to be a key adhesion receptor mediating leukocyte recruitment into lesions and promoting advanced atherosclerosis in apoE-deficient mice.     

Lactoferrin in Pure Pancreatic Juice in Chronic Pancreatitis

To investigate the role of lactoferrin in intraductal protein precipitates in chronic pancreatitis, lactoferrin was measured in pure pancreatic juice collected by endoscopic retrograde pancreatic cannulation using a sensitive and specific radioimmunoassay. Significant gradual increase in the lactoferrin concentration and output was observed in chronic pancreatitis (mean +/- SE = 1.13 +/- 0.04 microgram/ml, 1.61 +/- 0.44 microgram/min for five controls; 4.73 +/- 0.70 microgram/ml, 14.1 +/- 2.86 micrograms/min for 15 patients with noncalcified mild chronic pancreatitis; 23.6 +/- 4.7 micrograms/ml, 28.4 +/- 13.4 micrograms/min for four with chronic pancreatitis with visible protein plugs or calculi). The total protein in the juice gradually decreased in chronic pancreatitis (12.8 +/- 1.48 mg/ml for control, 7.6 +/- 1.37 for noncalcified, 5.2 +/- 1.27 for patients with plugs or calculi). Lactoferrin appears to rise as the disease progresses and although this may be important etiologically, it may also just be an accompanying protein which increases as the disease progresses.     

Trends in obesity in young adults in The Netherlands from 1974 to 1986

Data from two screening projects on cardiovascular risk factors were used to investigate trends in body mass index (BMI; weight(kg)/height(m)2) and in the prevalence of obesity in The Netherlands between 1974 and 1986. In the period 1974-80 about 30,000 men and women aged 37-43, with a mean age of 40, were screened. In the period 1981-6 about 80,000 men aged 33-37, with a mean age of 35, were examined. In men, an increase in mean BMI of about 0.5 kg/m2 was observed between 1974 and 1980, which was reflected in an increase in the prevalence of a BMI between 27 and 30 kg/m2 of about 4 percentage points. In the period 1981-6, no change in mean BMI was observed in men, although there was a slight decrease in the percentage of men with a BMI between 25 and 27 kg/m2 (about 2 percentage points). In women, no change in mean BMI or in the prevalence of different grades of obesity was observed in the period 1974-80. The prevalence of grade I obesity (BMI 25-29.9 kg/m2) was 40-45 per cent in men aged 40 and 25-30 per cent in women aged 40 in the period 1974-1980. The prevalence of grade II obesity (BMI greater than or equal to 30 kg/m2) during that period was 5-6 per cent in men and 7-8 per cent in women. The prevalence of grade I and grade II obesity in men aged 35 was 35-40 per cent and 5-6 per cent respectively during the period 1981-6. The prevalence of grade II obesity in The Netherlands is comparable with that in some other Western European countries, but much lower than in the United States and Canada.     

Probability of stroke in Portugal in the next ten years]

AIM: To analyze the probability of stroke in Portuguese National Health Service patients in the next ten years. STUDY DESIGN: Application of the Framingham study protocol to stroke. RESULTS: We studied 20,005 patients, aged between 55 and 84 years. The probability of stroke increases with age. Comparative analysis between the number expected from the Framingham study and the Portuguese data shows the following results by age group: in men: 55-59 years: 9.6% (95% CI: 9.2-10.0); 60-64 years: 14.0% (95% CI: 13.5-14.6); 65-69 years: 19.5% (95% CI: 18.7-20.2); 70-74 years: 25.8% (95% CI: 25.0-26.7): 75-79 years: 31.2% (95% CI: 29.9-32.6); 80-84 years: 30.5% (95% CI: 28.9-32.2). In women: 55-59 years: 2.8% (95% CI: 2.6-3.0); 60-64 years: 7.2% (95% CI: 6.8-7.6); 65-69 years: 14.5% (95% CI: 13.8-15.1); 70-74 years: 20.5% (95% CI: 19.7-21.2); 75-79 years: 28.9% (95% CI: 27.8-30.0); 80-84 years: 30.4% (95% CI: 28.7-32.1). CONCLUSIONS: Based on these data it is possible to estimate the number of potential strokes in the next ten years in individuals aged between 55-84 years: 429,182 cases (95% CI: 410,881 to 447,932). If therapy were more effective, in accordance with the number expected from the Framingham study (254,113), 179,069 cases (95% CI: 156,768 to 193,819) could be prevented in Portugal, about 40% of all individuals who are at risk of suffering a stroke.     

Changes in uterine and ovarian blood flow during the oestrous cycle in rats.

The rates of uterine and ovarian blood flow during the oestrous cycle in rats were measured using radioactive microspheres. Blood flow was highest in the ovaries and uteri during pro-oestrus and lowest during metoestrus. During pro-oestrus, mean ovarian blood flow was 676-2 +/- 183-6 (S.D.) ml/min/100 g wet tissue and mean uterine blood flow was 249-7 +/- 120-1 ml/min/100 g. During metoestrus mean ovarian blood flow was 117-4 +/- 19-8 ml/min/100 g and mean uterine blood flow was 38-5 +/- 7-4 ml/min/100 g. In ovariectomized rats, uterine blood flow was 28-7 +/- 10-5 ml/min 100 g.     

Changes in insulin sensitivity and clearance in anorexia nervosa

Anorexia nervosa (AN) is a state of self-induced malnutrition characterized by a marked pursuit of thinness and the fear of obesity. Although low fasting blood glucose and insulin have been demonstrated, there is contradictory data on insulin sensitivity and a lack of information about insulin metabolism and its metabolic effects in AN. Insulin sensitivity, kinetics, and metabolic effects were measured using the euglycemic clamp in nine females with AN (age 25.2 +/- 1.9 years and 70.6 +/- 2.2% ideal body weight), and the results compared with seven female normal controls (NC) (age 23.6 +/- 1.0 years and 92.7 +/- 2.5% ideal body weight). Fasting plasma glucose (FPG), immunoreactive insulin (IRI), and C-peptide were significantly lower in AN as compared to NC (84.3 +/- 1.5 v 91.5 +/- 1.7 mg dL-1, 9.3 +/- 1.0 v 13.5 +/- 1.4 microU mL-1, and 0.26 +/- 0.03 v 0.41 +/- 0.02 pmol mL-1) (P less than 0.05). During the glucose clamp, the glucose metabolized (M), the metabolic clearance rate of glucose (MCRg), and the glucose metabolized per unit of insulin (M/I ratio) were all higher in AN as compared to NC (M, 8.7 +/- 1.2 v 6.9 +/- 0.6 mg min-1 kg-1; MCRg, 9.9 +/- 1.5 v 7.4 +/- 0.6 mL min-1 kg-1; M/I ratio, 8.6 +/- 1.6 v 5.0 +/- 0.3 mg min-1 kg-1/microU mL-1 X 100), but only the M/I ratio attained statistical significance (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Angiotensin-converting enzyme in serum and in bronchoalveolar lavage in sarcoidosis

Angiotensin-converting enzyme (ACE) determinations were made in serum and in bronchoalveolar lavage fluid in 20 controls and in 28 patients with sarcoidosis. Serum ACE was significantly higher in patients with active sarcoidosis (54.3 +/- 19.0 SD nmol/ml/ min; n = 24) compared to controls (25.7 +/- 8.2; n = 20) or to patients with inactive sarcoidosis (23.6 +/- 7.3; n = 4). In contrast, ACE in bronchoalveolar lavage fluid was similar in nonsmoking controls (16.4 +/- 7.3 nmol/ml/min/macrophage; n = 8), smoking controls (10.4 +/- 11.9; n = 7); nonsmoking active sarcoidosis patients (16.7 +/- 14.6; n = 10), smoking sarcoidosis patients (17.9 +/- 8.4; n = 6) and inactive sarcoidosis patients (14.5 +/- 8.2; n = 3). Since ACE has been demonstrated by immunofluorescence in mononuclear phagocytes in granulomas, the authors speculate that macrophages recovered by alveolar lavage are not activated and do not reflect sarcoid alveolitis at the tissue level.     

Haptoglobulin phenotypes in leprosy

Haptoglobulin phenotyping was carried out in fifty controls and in thirty five leprosy patients. In controls the incidence Hp phenotypes 2-2, 2-1 and 2-1 (Mod) is 76%, 16% and 8% respectively. In leprosy patients, the incidence of phenotypes 2-2, 2-1, 1-1 and 0-0 is 77%, 11%, 3% and 9% respectively. The incidence of phenotype 2-2, 1-1 and 0-0 is more in leprosy patients than in controls and is significant (p less than 0.05). In none of the leprosy patients phenotype 2-1 (Mod) was recorded.     

Glucocorticoid receptors in lymphocytes in anorexia nervosa

OBJECTIVE: The aim was to explore the down-regulation of the glucocorticoid receptors during hypercortisolaemia in anorexia nervosa. DESIGN: Urine and plasma samples were obtained for cortisol determination and blood lymphocytes were isolated for receptor binding studies. PATIENTS: Sixteen anorexic patients, aged 16-27 years, with a mean +/- SEM body mass index of 14.2 +/- 2.0 (ranging from 11.1 to 17.4), and 15 normal women were studied. Six patients were reinvestigated after a significant weight gain. MEASUREMENTS: The binding capacity and affinity of the glucocorticoid receptors were measured with dexamethasone as ligand on lymphocytes. RESULTS: In patients, both total and free plasma cortisol concentrations were higher than in the normal women, as was their urinary free cortisol; the number of glucocorticoid receptors per cell (Ro) and the binding affinity (Kd) for dexamethasone were, however, not significantly different (Ro: 7687 +/- 1750 vs 7347 +/- 1285 sites/cell; Kd: 7.7 +/- 2.4 vs 7.4 +/- 1.7 nM at 24 degrees C). After weight gain (14 +/- 2 to 16 +/- 2 kg/m2), receptor numbers were 8421 +/- 2126 (pre) and 9011 +/- 500 (post) sites/cell, which are not significantly different (P greater than 0.2); the Kd was unchanged (9.3 +/- 2.6 vs 9.2 +/- 2.4 nM). CONCLUSIONS Hypercortisolaemia does not down-regulate the lymphocyte glucocorticoid receptors in anorexia nervosa and a post-receptor defect might be involved in peripheral tissue resistance to the effects of glucocorticoid hormones in undernutrition.     

The role of sensory nerves in propranolol-induced bronchial hyperresponsiveness in the guinea-pig

The racemic mixture propranolol (RS-(+/-)-, and the S-(-)- and R-(+)-) isomers of propranolol have been shown to induce bronchial hyperresponsiveness in the guinea-pig unrelated to beta-adrenoreceptor occupancy, that is attenuated by vagal section and mediated via the generation of 5-lipoxygenase metabolites of arachidonic acid. We have investigated the role of sensory nerves in propranolol-induced bronchial hyperresponsiveness in guinea-pigs. Airways responsiveness to acetylcholine, bradykinin and bombesin was determined before and 10 min after intravenous infusion with RS-(+/-)-, S-(-)- and R-(+)-propranolol (1 mg/kg) in vehicle and capsaicin-treated guinea-pigs. Propranolol (1 mg/kg, iv) significantly augmented the bronchoconstrictor response to acetylcholine, bradykinin and bombesin (P<0.001), an effect that was observed for RS-(+/-)-, S-(-)- and R-(+)-propranolol. In capsaicin-treated animals, the increased airways responsiveness to acetylcholine following intravenous infusion of S-(-)-propranolol was significantly inhibited. Capsaicin treatment tended to reduce the increase in airways responsiveness to bradykinin following infusion with R-(+)-propranolol, but was only significant for the highest dose used. Similarly, capsaicin treatment had no effect on the ability of RS-(+/-)-, S-(-)- and R-(+)-propranolol to enhance the bronchoconstrictor response to bombesin. Our results suggest that propranolol-induced bronchial hyperresponsiveness to certain spasmogens is in part mediated by the action of capsaicin-sensitive nerves.     

Characteristics of renal disease in hypertensive morbidities in adults in Burkina Faso

In the aim to determine the importance of renal disease in hypertensives (BP > 160/95 mmHg), we conducted a retrospective study in Burkina Faso, a black african country. 342 adults hypertensive (200 men, 142 women, mean age: 50.6 +/- 13.8 years) hospitalized in the departments of Cardiology or Internal medicine from January 1995 to December 1997 were included. Patients were at their first hospital stay in 273 cases (79.8%). When technical conditions were available, assessments were systematically done. Blood pressure was 183.6 +/- 36.4/113.3 +/- 23.1 mmHg. Total morbidity concerned 316 patients (92.4%). Cardiovascular complications (CVC) have been diagnosed in 236 patients (69%) with a mean age of 51.6 +/- 14 y, neurologic complications (NC) in 85 patients (24.9%, mean age: 55.7 +/- 12) and renal disease (RD) in 123 patients (36%; mean age: 44.7 +/- 14.5 y). Mean age of single RD (n: 27, mean age: 39.5 +/- 12.8 y) was significantly lower than no complicated hypertensives (n: 42, mean age: 48.2 +/- 11.6 y) or single CVC (n: 104, mean age: 55 +/- 12.5) or single NC (n: 34, mean age: 55.1 +/- 11.1) or associated comorbidities (n: 135, mean age: 49.1 +/- 14.5). Patients under 40 years of age have had higher 24 hours proteinuria than other patients (1.05 +/- 1.17 g (n: 51) vs 0.45 +/- 0.68 (n: 170), p < 0.01). Chronic renal failure occurred in youngest patients (n: 72, age: 39.7 +/- 13.4 vs 53.7 +/- 12.3; p < 0.01) with a most high prevalence in rural (31.6%) than urban patients (15.8%; p < 0.01). End stage renal failure concerned 49 patients (mean age: 35.9 +/- 12.7). 27 patients died during hospital stay by renal failure in 17 cases (mean age: 37 +/- 11). CVC in 5 cases (mean age: 68.6 +/- 8) and NC in 5 cases (mean age: 60.2 +/- 9.2). Among survivals, 72 patients (28.9%) were of a bad short-term prognosis and 38 had end stage renal failure. In conclusion, our data suggest that renal disease will be common cause of hypertension and also a selective factor for long term survival of hypertensives in a country where renal replacement therapy is not available.