Redistribution of haloperidol after electroshock: experimental evidence

We have previously reported that plasma and red blood cell levels of haloperidol, a neuroleptic agent, significantly increased immediately after electroconvulsive shock therapy (ECT) in schizophrenic patients on long term haloperidol treatment. To elucidate the mechanism of this increase, we attempted to reproduce this phenomenon in female Wistar rats. After 4 successive days of ip administration of haloperidol (10 mg/kg body weight, once daily), rats were given ECT through corneal electrodes on the fifth day (a.c. 50 Herz, 55 mA, 2.0 sec). Haloperidol levels were determined in plasma and other major tissues using a radioreceptor assay for haloperidol distribution before and after ECT at appropriate time intervals. Plasma haloperidol level was significantly increased 1 min after ECT but tended to return to the control level (without ECT) after 5 min. A significant decrease in haloperidol concentration in tissues was not observed in any of the tissues examined including frontal cerebrum, striatum, and muscle tissues (gluteal muscles). However, the relatively high haloperidol level and the large volume of muscle tissues suggested that the muscle could be the source of the transient increase in haloperidol levels in plasma. This conclusion was also supported by the data showing no significant rise of plasma haloperidol level after ETC in rats previously given a muscle relaxant, succamethonium chloride.     

Mechanism for the increase in plasma renin activity by pentobarbital anesthesia

The mechanism by which pentobarbital anesthesia causes increases in plasma renin activity (PRA) was examined in dogs infused with either propranolol or indomethacin, an inhibitor of prostaglandin synthetase. Infusion of propranolol at 1 mg/kg, (I.V.) followed by 0.6–0.7 mg/kg/hr decreased PRA from 6.98±2.49 ng/m1/hr during control periods to 1.58±0.79 ng/m1/hr 30 minutes after the injection of propranolol (P<0.025). Subsequent induction of anesthesia with sodium pentobarbital caused PRA to rise to 3.87±0.93 ng/m1/hr in 30 minutes. (P<0.01). Plasma potassium concentration decreased from 4.6±0.2 mEq/L to reach 4.0±0.1 mEq/L 30 minutes after induction of anesthesia (P<0.005). Infusion of indomethacin at 5 mg/kg, (I.V.) followed by 1.5 ? 3.1 mg/kg/hr into conscious dogs did not decrease PRA. In contrast to the report by Montgomery et al (Fed. Proc. 36: 989, 1977), we found that the increase in PRA after pentobarbital anesthesia could not be blocked by indomethacin. PRA was 5.3±1.2 ng/m1/hr(M ± SEM) during control periods and was 4.7±1.4 ng/m1/hr 30 minutes after the infusion of indomethacin (P<0.1). PRA increased to 10.9±2.3 ng/m1/hr, 9.2±2.2 ng/m1/hr, and 7.7±1.7 ng/m1/hr at 5, 15 and 30 minutes, respectively, after the administration of pentobarbital (P<0.005, P<0.025, P<0.05). PRA declined to 4.2±1.3 ng/m1/hr 60 minutes after pentobarbital anesthesia (P<0.1). It is concluded that the mechanism by which pentobarbital causes increases in PRA is independent of prostaglandins.     

枸杞多糖对鲤生长性能和肝胰脏抗氧化能力的影响

为探索枸杞多糖(Lycium barbarum polysaccharide,LBP)对鲤生长性能及肝胰脏抗氧化能力的影响,在试验饲料中分别添加比例为0、0. 005%、0. 01%、0. 015%、0. 02%的枸杞多糖,配制成5种等氮等能试验饲料。以450尾平均初始体质量为(10. 57±0. 89)g的健康鲤为试验对象,随机分为5组,每组3个重复,每个重复30尾试验鱼,分别投喂5种试验饲料,养殖时间为56 d。结果发现,鲤增重率(weight gain ratio,WGR)、特定生长率(specific growth ratio,SGR)均在枸杞多糖添加量为0. 005%时最大,分别为(118. 45±23. 80)%、(1. 39±0. 20)%/d,且差异显著(P0. 05)。枸杞多糖添加量大于0. 005%后,WGR,SGR则呈微弱下降的趋势,但差异不显著(P0. 05);饲料系数(feed conversion ratio,FCR)随着枸杞多糖添加量的提高而呈先降低后升的变化趋势,在0. 005%时最小,为1. 54±0. 24(P0. 05);添加量大于0. 005%后,FCR则呈上升趋势,且差异显著(P0. 05)。随着枸杞多糖添加量的提高,鲤肝胰脏超氧化物歧化酶(superoxide dismutase,SOD)、过氧化氢酶(catalase,CAT)活性均呈现先升高后降低的变化趋势,均在枸杞多糖添加量为0. 005%时最高,分别为(110. 85±7. 51)U/mg、(104. 58±4. 53)mg/(g·min)(P0. 05);添加量大于0. 005%后,SOD活性呈微弱的下降趋势。CAT则在其添加量大于0. 01%后呈微弱的下降趋势(P0. 05);丙二醛(malondialdehyde,MDA)含量则呈先降低后升高的趋势,在添加量为0. 01%时最低,为(0. 73±0. 81)nmol/mg,但差异不显著(P0. 05)。研究说明添加一定比例的枸杞多糖可提高鲤对饲料的利用率,促进其生长,提高鲤机体的抗氧化能力,且综合考虑,鲤饲料中枸杞多糖的适宜添加水平为0. 005%。     

Retrospective analysis of CT-guided percutaneous cryoablation for treatment of painful osteolytic bone metastasis

This study aimed to evaluate the safety and effectiveness of CT-guided percutaneous cryoablation for treatment of painful osteolytic bone metastases. A total of 26 patients (36 bone metastases) treated with CT-guided percutaneous cryoablation between May 2012 and June 2016 were enrolled in this retrospective study. All procedures were performed under local anesthesia. A visual analog scale (VAS) was used to evaluate pain before the procedure and at 1 day, 1 month, 3 months, and 6 months after the procedure. Complications during and after the procedure were recorded and graded by the Clavien–Dindo classification. The mean VAS pain score was 7.1 ± 1.1 (range, 4–10) before cryoablation. It was significantly lower at all timepoints after treatment: 2.1 ± 1.7 (P < 0.0001) at 1 day after treatment, 1.3 ± 1.8 (P < 0.0001) at 1 month, 1.6 ± 1.7 (P < 0.0001) at 3 months, and 1.8 ± 1.3 (P < 0.0001) at 6 months. The response rates were 91.7%, 94.4%, 91.7%, and 94.4%, respectively, at 1 day, 1 month, 3 months, and 6 months after cryoablation; the complete response rates were 22.2%, 41.7%, 36.1%, and 22.2%, respectively. Adverse events (skin frostbite, nerve injury, pathologic fracture) occurred in 3 patients. CT-guided percutaneous cryoablation under local anesthesia appears to be a safe and effective treatment for painful osteolytic bone metastases. Prospective clinical trials on large samples needed to confirm this conclusion.     

Antioxidant status and lipid peroxidation in hemodialysis patients undergoing erythropoietin and erythropoietin-vitamin E combined therapy

In this study, plasma and red blood cell (RBC) antioxidant status and plasma lipid peroxidation were investigated in 46 hemodialysis patients. In addition, the effect of erythropoietin (EPO) and EPO-vitamin E combination therapy on plasma and RBC antioxidant status, and plasma lipid peroxidation were examined.

There were 10 healthy subjects in the control group and 10 hemodialysis patients in the untreated group. The third group included 36 hemodialysis patients that were given EPO (100 U/kg) for 3 months, 3 times per week. The fourth group included 36 hemodialysis-patients from the EPO group that were given EPO at a 50% decreased dose + vitamin E (300 mg/day) for 3 months.

MDA levels in the untreated group, the EPO group and the EPO + vitamin E groups were found to be higher than the control group (p<0.001, in both). Furthermore, MDA levels in both of the treatment groups were lower when compared to the untreated group (p<0.001, in both). Plasma vitamin E levels in the untreated, the EPO group and EPO + vitamin E groups were lower than the control group (p<0.001). In contrast, plasma vitamin E levels in the treatment groups were higher in comparison with the control group (p<0.05). SOD activities in the untreated, the EPO group and the EPO + vitamin E groups were found to be lower than the control group (p<0.001). SOD activities in the treatment groups were higher than the control group (p<0.001). The SOD activities in the EPO + vitamin E group increased when compared to the EPO group (p<0.001). CAT activities in the untreated, the EPO group and the EPO + vitamin E groups were found to be lower than the control group (p<0.001 in untreated and EPO groups, p<0.01 in EPO + vitamin E group). CAT activities in EPO and EPO + vitamin E groups were increased when compared to the untreated group (p<0.01).

In conclusion, our findings have shown that antioxidant status decreased and lipid peroxidation increased in hemodialysis patients. EPO has an antioxidant effect on the RBC and plasma antioxidant status, and plasma lipid peroxidation. These effects were moderately increased by the combination of vitamin E and EPO.     

Synchronization of estrus in goats: The relationship between eCG binding in plasma,time of occurrence of estrus and fertility following artificial insemination

Radioimmunoassay (RIA) was used to measure plasma eCG binding in dairy goats (n = 524) at the beginning of a progestagen/eCG treatment and 25 d after eCG administration. The eCG binding was not dependent on the age of the females but increased with the number of treatments they had previously received (3.4 % ± 4.8, n = 47 vs 9.6 % ± 13.2, n = 249; mean ± SD; P < 0.01 for goats treated 0 and 1 time vs those treated 2 to 5 times, respectively). The synchronization treatment led to an increase in the binding of eCG (7.1 % ± 10.9 before vs 28.3 ± 24.5 after treatment; P < 0.01). When eCG binding before treatment was higher than 5 % the onset of estrus was delayed: 37.9 % of goats came into estrus more than 30 h after sponge removal vs 7.4 % when eCG binding was lower than 5 % (P < 0.01). Fertility was significantly decreased when eCG binding was higher than 10 %. These results show that the repetition of treatment with eCG to induce estrus in goats increases eCG binding. This could explain the lowered efficiency of the hormonal treatment to synchronize estrus and the associated decrease in fertility when goats are inseminated at a predetermined time.     

Single-step,rapid separation of acidic and basic isoenzymes from commercial horseradish peroxidase

A simple and sensitive high-performance liquid chromatography method with electrochemical detector is described for the determination of free 3-methoxy-4-hydroxyphenylacetic acid (HVA) in human plasma. The method does not involve any extraction, is specific and reproducible, and has the potential to measure serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) simultaneously. The plasma concentration of free HVA in eight normal, healthy adult volunteers was 10.9 ± 4.6 (mean ± SD). In a preliminary study, in one schizophrenic patient the plasma HVA increased twofold after neuroleptic treatment.     

Oxidative Stress in Severely Obese Persons Is Greater in Those With Insulin Resistance

The postprandial state seems to have a direct influence on oxidative status and insulin resistance. We determined the effect of an increase in plasma triglycerides after a high‐fat meal on oxidative stress in severely obese patients with differing degrees of insulin resistance. The study was undertaken in 60 severely obese persons who received a 60‐g fat overload with a commercial preparation. Measurements were made of insulin resistance, the plasma activity of various antioxidant enzymes, the total antioxidant capacity (TAC) and the plasma concentration of thiobarbituric acid reactive substances (TBARS). The patients with greater insulin resistance had a lower plasma superoxide dismutase (SOD) activity (P < 0.05) and a greater glutathione peroxidase (GSH‐Px) activity (P < 0.05). The high‐fat meal caused a significant reduction in SOD activity and an increase in the plasma concentration of TBARS in all the patients. Only the patients with lower insulin resistance experienced a significant increase in plasma catalase activity (2.22 ± 1.02 vs. 2.93 ± 1.22 nmol/min/ml, P < 0.01), remaining stable in the patients with greater insulin resistance. These latter patients had a reduction in plasma TAC (6.92 ± 1.93 vs. 6.29 ± 1.80 mmol/l, P < 0.01). In conclusion, our results show a close association between the degree of insulin resistance and markers of oxidative stress, both before and after a high‐fat meal. The postprandial state causes an important increase in oxidative stress, especially in severely obese persons with greater insulin resistance. However, we are unable to determine from this study whether there is first an increase in oxidative stress or in insulin resistance.     

Effect of electroconvulsive therapy without anticonvulsive premedication on serum growth hormone in man.

Serum concentrations of human growth hormone (HGH) were measured in psychiatric patients during the first, third and sixth electroconvulsive therapy (ECT) without anticonvulsive premedication. Serum HGH increased 30 min after the application of current and no differences were found between responses to 1st, 3rd, or 6th ECT. Maximal increase of serum glucose was seen after the first ECT and gradual decreases after the 3rd and 6th ECT were observed     

Persistence and recovery of regressing 3-mm ovarian follicles in heifers

The persistence and outcome of 3-mm follicles before the emergence of follicular wave 1 were studied every 6 hours in 15 heifers beginning on Day 14 (Day 0 = ovulation). A mean of 9.1 ± 1.3 persistent 3-mm follicles (P3Fs) per heifer was detected with persistence for 3.5 ± 0.1 days. The P3Fs either regressed continuously and remained in the 3-mm range (3.0–3.9 mm) or regressed but with a transient increase in diameter during regression. Some (43%) P3Fs were rescued to become growing follicles in wave 1. The number of follicles that became part of wave 1 was less (P < 0.0001) for follicles that originated from a P3F (4.2 ± 1.0 P3Fs) than for follicles that did not originate from a P3F (11.9 ± 1.6 follicles). The day of rescue of wave 1 follicles from a P3F (Day −1.1 ± 0.6) was earlier (P < 0.001) than for emergence of follicles at 3 mm that did not originate from a P3F (Day −0.5 ± 0.5). A cluster of 5.1 ± 0.6 P3Fs was identified in 10 of 15 heifers by the synchronized peaks of transient diameter increases at the 6-hour interval corresponding to Day −4.0 ± 0.3. Concentrations of FSH oscillated at 12-hour intervals with a peak (P < 0.05) 6 hours before and 6 hours after the beginning of a transient diameter increase during a P3F. Concentration of FSH was greater (P < 0.02) in heifers with a high number (11–18) of P3Fs per heifer (0.27 ± 0.02 ng/mL) than with a low number (2–9) per heifer (0.17 ± 0.008 ng/mL). Results supported the novel hypothesis that 3-mm follicles may persist for two or more days and may be rescued to become growing follicles of wave 1.     

Polycystic Ovary Syndrome: Clinical Presentation in Normal-weight Compared with Overweight Adolescents

ObjectiveTo characterize polycystic ovary syndrome (PCOS) in adolescents and determine whether a distinct clinical presentation differentiates normalweight (NW) from overweight (OW) PCOS.MethodsRetrospective chart review of patients seen in a tertiary care center from 19982008 who met the National Institutes of Health and/or Rotterdam criteria for PCOS (N = 211; NW = 43, OW = 168). We collected data on clinical features, biochemical markers, and ultrasound findings.ResultsPatient age ranged from 11.3 to 20.3 years (mean, 15.7 ± 1.7 years), and body mass index (BMI) from to 64.2 kg/m² (mean, 31.7 ± 7.7 kg/m²). Seventy one percent of patients were Caucasian, 85% had irregular menses, 69% reported hirsutism, 18% had moderate to severe acne, 91% had a high free androgen index (FAI), and 8% had abnormal thyroidstimulating hormone (TSH) levels. The BMIstandard deviation (SD) score was 0.1 ± 5 in NW and 3.4 ± 1.8 in OW girls. NW girls were older at diagnosis (16.4 ± 1.4 years vs. 15.5 ± 1.7 years; P = .0006) than OW girls, less likely to have a family history of obesity (22% vs. 65%; P<.0001), and less likely to have acanthosis nigricans (11% vs. 68%; P<.0001). NW girls were more likely to have polycystic ovaries on ultrasound (88% vs. 52%; P = .01) and a lower FAI (7.3 ± 4.5 vs. ± 12.9; P<.0001). The BMISD score was negatively associated with sex hormone binding globulin (r_s = 0.52; P<.0001) and positively associated with FAI (r_s = 0.42; P<.0001).ConclusionNW girls are more likely to be older at diagnosis and have polycystic ovaries. Other differences in presentation between groups were attributable to differences in weight. NW PCOS is likely part of a continuous spectrum of clinical PCOS rather than a distinct entity. (Endocr Pract. 2013;19:471478)     

Effects of dietary forage-to-concentrate ratios on performance and carcass characteristics of growing fat-tailed lambs

This study was conducted to evaluate the effects of using different dietary forage-to-concentrate ratios on growth performance and carcass characteristics of eighty Chall male fat-tailed lambs, averaging 165 ± 15 (SD) days of age and body weight of 38.4 ± 4.8 (SD) kg, randomly assigned to four diets containing alfalfa hay-to-concentrate ratios (DM basis) of 70:30 (C30), 50:50 (C50), 30:70 (C70), 10:90 (C90). Metabolizable energy (ME) contents were, 9.12. 9.96, 10.67, and 11.34 MJ/kg dry matter (DM) and crude protein (CP) contents were 143, 152, 161, and 174 g/kg for the C30, C50, C70, and C90 diets, respectively. Sixteen lambs (4 lambs/treatment) were slaughtered at the end of feeding period (84 days). Dry matter intake and feed conversion ratio (FCR) (i.e., kg DM/kg gain) decreased linearly (P<0.001) as concentrate level increased in the diet. However, a linear increase (P<0.001) for ME intake and a quadratic increase for average daily gain (ADG, P<0.001) and final body weight (P<0.01) were observed with increasing dietary concentrate. Slaughter weight, eye muscle area, and weights of lean, bone, neck, shoulder, rack–loin, leg, skin, head, lung, and spleen were not affected by the experimental diets. However, as dietary concentrate increased, a linear increase for dressing percentage, feet weight (P<0.001), and backfat thickness (P<0.02), a quadratic increase for empty body weight (EBW, P<0.02), weights of hot and cold carcass (P<0.001), subcutaneous fat (P<0.02), total fat (P<0.01), brisket–flank (P<0.04), and tail fat (P<0.001), a linear decrease for weights of liver (P<0.01), and heart (P<0.05), and a quadratic decrease for lean-to-fat ratio (P<0.02) were observed. This study indicates that in Chall fat-tailed lambs the increase of dietary concentrate (up to 700 g/kg) improves growth rate, FCR and dressing percentage with negative effect on carcass lean-to-fat ratio.     

Morphokinetic changes and apoptotic cell death in vitrified and non-vitrified in vitro-produced ovine embryos

This article addresses morphokinetic changes and the extent of apoptosis in vitrified and non-vitrified in vitro-derived ovine blastocysts. Cumulus-oocyte complexes were collected after ovarian scarification obtain after slaughter and in vitro maturation was performed in TCM 199 medium supplemented with Earle’s Salt, 10 % of FBS, and 5 µg/mL of LH/FSH at 38 °C for 24 h. After maturation, the oocytes were co-incubated with thawed ram semen (IVF) for 19 h.Embryo development was monitored with the aid of the Primo Vision Time-Lapse (TL) system. Twenty-five out of thirty-one ovine blastocysts that were vitrified using the Cryotop system at the early blastulation stage of development subsequently re-expanded. Both the vitrified (n = 25) and non-vitrified (control group: n = 28) blastocysts were examined for detection of apoptosis (TUNEL assay) and total blastomere counts at the time they attained the expanded blastocyst stage. Blastocyst formation occurred earlier in non-vitrified than in vitrified ovine embryos (147:49 ± 20:23 compared with 156:46 ± 19:24; hours:minutes post-insemination; mean ± SD; P < 0.05). The average number of blastocyst collapses was greater (2.45 ± 1.64 compared with 1.45 ± 1.64), but the number of weak contractions was less for vitrified than non-vitrified ovine blastocysts (P < 0.05). The mean number of blastomeres was greater (131.8 ± 38.6 compared with 91.5 ± 18.3; P < 0.05) while the number of TUNEL-positive cells (4.4 ± 1.6 compared with 6.3 ± 2.3) and apoptotic index (3.4 ± 1.2 % compared with 6.9 ± 2.6 %) were less (P < 0.05) in non-vitrified compared with vitrified blastocysts. Vitrification of ovine embryos was associated with a delayed blastocyst formation, greater numbers of apoptotic cells, significant reduction in the number of blastomeres, and higher/lower incidence of blastocyst collapse/weak contractions.     

Effect of nicotine on in vivo secretion of melanocorticotropic hormones in the rat

Corticosterone, ACTH, β-endorphin and α-MSH were measured in rat plasma by radioimmunoassay before and 2,5,15,30 minutes after an intraperitoneal injection of nicotine (500 μg/Kg b.w.). Nicotine induced an increase of plasma corticosterone (p < 0.05 at t + 15 min), ACTH and β-endorphin (p < 0.01 at t + 5 min) and a decrease of α-MSH (p < 0.005 at t + 15 min). Dose response experiments showed an increase of corticosterone, ACTH, β-endorphin 15 min after 250 μg/Kg b.w. nicotine I.P., no effect being observed after injection of 100 μg/Kg b.w. The decrease of α-MSH was observed 15 min after 100, 250 or 500 μg/Kg b.w. nicotine I.P. Our results suggest that the increase of corticosterone is mediated through ACTH release.     

Men and women show different adaptations of quadriceps activity following fatiguing contractions: An explanation for the increased incidence of sports-related knee injuries in women?

We investigated whether adaptations of quadriceps muscle activity to fatiguing exercise differs between sexes. Fifteen healthy men (age, mean ± SD; 22. ± 2.4 yr, body mass 70.5 ± 11.4 kg, height 1.72 ± 0.06 m) and 15 healthy women (age, mean ± SD; 21 ± 1.8 yr, body mass 60 ± 7.5 kg, height 1.62 ± 0.07 m), all right leg dominant, participated in the study. Participants performed a submaximal isometric knee extension contraction at 50% of the maximum voluntary contraction (MVC) sustained until task failure before and after a fatiguing exercise. Surface electromyography (EMG) was simultaneously recorded from nine regions distributed over the medial, middle and lateral locations of the quadriceps muscles in a longitudinal direction corresponding to the vastus medialis, rectus femoris (RF) and vastus lateralis muscle, respectively. A significant reduction in maximal force and time to task failure were observed after fatiguing exercise for both sexes (P < 0.001). However, women displayed greater myoelectric manifestations of fatigue specifically for the RF during the post-fatigue sustained contraction (P < 0.05). The RF is more susceptible to fatiguing exercise in women compared to men which may partly explain the higher risk of knee injuries among female athletes during competitive sports.     

Correlation between sperm creatine phosphokinase activity and sperm concentrations in normospermic and oligospermic men

Toward the development of biochemical probes for the assessment of sperm function we have measured the activities of sperm creatine-N-phosphotransferase (CPK). There was a highly significant inverse correlation (P < 0.001 in all comparisons) between sperm CPK activities and sperm concentrations in specimens of normospermic and oligospermic men with > 30 million sperm/ml (0.106 ± 0.01 SEM, Nequals;90, expressed as CPK U/100 million sperm), 20–30 million sperm/ml (0.333 ± 0.07 SEM, Nequals;30) and 10–20 million sperm/ml (0.583 ± 0.12 SEM, Nequals;30) when compared with the CPK values of the < 10 million/ml specimens (2.242 ± 0.46 SEM, Nequals;30). Furthermore, the distribution of CPK activities within these four groups showed that 96%, 67%, 43%, and 4% of the samples, respectively, were in the < 0.250 CPK U/100 million sperm normal range (mean + 2 SD of the > 30 million sperm/ml group). However, there was no relationship between sperm CPK activities and the values of sperm motility (P > 0.15) or morphology (Pequals;0.38) in the samples. The migrated sperm fractions (significantly improved in motility and velocity parameters) showed CPK activities lower than the initial semen specimens (P < 0.01, Nequals;150). In fact, in some oligospermic men the CPK activities of the migrated sperm fractions were within the range of normospermic samples. The data suggest that sperm CPK values in the initial specimens and the degree of improvement in the migrated sperm fractions reflect the relative concentrations of a “normal” sperm subpopulation. We propose that CPK activities and similar objective biochemical parameters may be important in predicting sperm quality and the fertilizing potential of oligospermic men.     

Selenium status of healthy immigrant parisian preschool children

Plasma selenium (Se) concentration and erythrocyte glutathione peroxidase activity (GPx) were assessed in a population of healthy preschool children two to five years old, residing in the city of Paris. In the 118 subjects, mean (±SD) plasma Se concentration was 62.10 ±13.96 μg/L, and mean GPx activity was 23.58±8.52 U/g Hb. Mean plasma Se of male children was significantly (p=0.001) higher (12%) than levels of girls. Plasma selenium levels were not correlated with erythrocyte GPx activity. Children from Mediterranean origin had a slightly lower erythrocyte GPx activity (p<0.05) than children from other regions. Mean plasma Se concentration of this group corresponded to the lower limit of intervals, which characterizes geographical regions of intermediate selenium concentrations.     

Relationship Between Muscle Sympathetic Nerve Activity and Plasma Leptin Concentration

SNITKER, SØREN, RICHARD E PRATLEY, MARGERY NICOLSON, P ANTONIO TATARANNI, ERIC RAVUSSIN, Relationship between muscle sympathetic nerve activity and plasma leptin concentration. In humans, basal muscle sympathetic nerve activity (MSNA), a direct measure of sympathetic nervous outflow, is correlated with percentage of body fat. The underlying physiological mechanism is unknown. On the basis of the observation that leptin increases sympathetic nervous outflow in the oblob mouse, we hypothesized that leptin, a hormone secreted by the adipose tissue, may act as a peripheral signal to increase sympathetic nervous outflow from the central nervous system. We therefore tested whether basal MSNA is correlated with plasma leptin concentration. Fasting plasma samples and recordings of basal MSNA in the peroneal nerve were obtained from 37 healthy, nondiabetic men (35 whites and 2 Mexican-Americans; 29 ± 7 years, 86 ± 14 kg, 24 ± 10% body fat; mean ± SD) who were fed a weight-maintenance diet on a metabolic ward. As expected, plasma leptin concentration (geometric mean, 6.4 ng/mL; 95% confidence interval, 4.6 ng/mL to 9.0 ng/mL) correlated with % body fat (r=0.93, p<0.001). Basal MSNA was 31.6 ± 10.0 bursts/min and correlated with % body fat (r=0.53, p<0.001) and with plasma leptin concentration (r=0.44, p<0.01). In conclusion, the results demonstrate a correlation between MSNA and plasma leptin concentration of a magnitude similar to that between MSNA and % body fat. Leptin may therefore be the peripheral signal explaining the correlation between MSNA and % body fat. A full understanding of the relationship between leptin and the activity of the sympathetic nervous system requires further studies, including the administration of leptin in humans.     

Aggregation of erythrocytes and their membranes flexibility in patients with cancer-associated anemia: Mechanisms of changes under the influence of epoetin alfa

The relationships between the red blood cell (RBC) membrane elasticity and RBC aggregation in healthy individuals and in patients with anemia of malignant tumors treated with human erythropoietin drug epoetin alfa (EA) were analyzed. It was found that prior to the treatment of patients, incubation of RBCs with EA was accompanied by an increase of RBC deformability and the reduction of their aggregation (RBCA). In these circumstances the two characteristics of the RBC microrheology correlated negatively with each other (r =–0.734, p < 0.05). In contrast, aggregation and deformability of RBCs from healthy individuals increased under the influence of EA and positively correlated with each other (r = 0.580, p < 0.05). After a 4-week treatment of patients with EA, aggregation response of the patients’ RBCs was increased by 29% (p < 0.05) and was close to that of healthy RBCs. This change of the RBC aggregation response may be connected with an alteration of the sensitivity of the membrane cationic channel to EA and an increase of the cell deformability. This possibility was supported by experiments with the use of Ca²⁺-channel blocker verapamil and Ca²⁺-chelating agent EDTA. Under these conditions a decrease of the RBC aggregation varied from 40 to 50% (p < 0.05). It was suggested that the effectors of calcium regulatory cascade upon exposure to EA may be membrane integrin receptors of type IIb–IIIa. This assumption was confirmed by experiments employing the inhibitors of these receptors (tirofibam and integrelin) and a preparation of monoclonal antibodies against IIb–IIIa receptors (monafram), which produced a significant decrease (20–30%, p < 0.05) of the RBC aggregation. Thus, our findings suggest that the altered aggregation response of RBCs in anemic patients with malignant tumors can be restored by the correction of anemia with epoetin alfa.     

Apple and blackcurrant polyphenol-rich drinks decrease postprandial glucose,insulin and incretin response to a high-carbohydrate meal in healthy men and women

Postprandial glycemic responses to meals are inhibited by polyphenol-rich plant foods. Combinations of polyphenols may be particularly effective through complementary mechanisms. A randomized, controlled, double-blinded cross-over trial was conducted in healthy volunteers to test the hypothesis that apple and blackcurrant polyphenol-rich drinks would reduce postprandial blood glucose concentrations. Secondary outcomes included insulin and glucose-dependent insulinotropic polypeptide (GIP) secretion. Twenty men (mean age 26 y, SD 8) and 5 postmenopausal women (mean age 57 y, SD 3) consumed a placebo drink (CON) and 2 polyphenol-rich drinks containing fruit extracts: either 1200 mg apple polyphenols (AE), or 600 mg apple polyphenols+600 mg blackcurrant anthocyanins (AE+BE), in random order with a starch and sucrose meal. Incremental areas under the curve (iAUC) for plasma glucose concentrations were lower following AE+BE over 0–30 and 0–120 min compared with CON; mean differences (95% CI) −32 mmol/L·min (−41, −22, P<.0005) and −52 mmol/L min (−94, −9, P<.05), respectively. AE significantly reduced iAUC 0–30 min (mean difference −26 mmol/L min, −35, −18, P<.0005) compared with CON, but the difference over 120 min was not significant. Postprandial insulin, C-peptide and GIP concentrations were significantly reduced relative to CON. A dose response inhibition of glucose transport was demonstrated in Caco-2 cells, including total and GLUT-mediated transport, and SGLT1-mediated glucose transport was strongly inhibited at all doses in Xenopus oocytes, following 10 min incubation with 0.125–4 mg apple polyphenols/ml. In conclusion, ingestion of apple and blackcurrant polyphenols decreased postprandial glycemia, which may be partly related to inhibition of intestinal glucose transport.