Analysis of Ly49 gene transcripts in mature NK cells supports a role for the Pro1 element in gene activation, not gene expression.

The variegated expression of murine Ly49 loci has been associated with the probabilistic behavior of an upstream promoter active in immature cells, the Pro1 element. However, recent data suggest that Pro1 may be active in mature natural killer (NK) cells and function as an enhancer element. To assess directly if Pro1 transcripts are present in mature Ly49-expressing NK cells, RNA-sequencing of the total transcript pool was performed on freshly isolated splenic NK cells sorted for expression of either Ly49G or Ly49I. No Pro1 transcripts were detected from the Ly49a, Ly49c or Ly49i genes in mature Ly49(+) NK cells that contained high levels of Pro2 transcripts. Low levels of Ly49g Pro1 transcripts were found in both Ly49G(+) and Ly49G(-) populations, consistent with the presence of a small population of mature NK cells undergoing Ly49g gene activation, as previously demonstrated by culture of splenic NK cells in interleukin-2. Ly49 gene reporter constructs containing Pro1 failed to show any enhancer activity of Pro1 on Pro2 in a mature Ly49-expressing cell line. Taken together, the results are consistent with Pro1 transcription having a role in gene activation in developing NK, and argue against a role for Pro1 in Ly49 gene transcription by mature NK cells.

Effectiveness of psychoeducation in reducing internalized stigmatization in patients with bipolar disorder.

This research was conducted as an experiment-control experimental study which aimed to determine the effectiveness of a psychoeducation program prepared to reduce internalized stigmatization. The study included 47 patients (24 experimental, 23 control) who had been diagnosed with bipolar disorder. At the end of the psychoeducation program, a significant decrease was observed in the total ISSMI mean scores, as well as in the ISSMI subscale mean scores for subscales such as alienation, approval of stereotypes, perceived discrimination and social withdrawal (p<0.05). The results demonstrated that a psychoeducation program designed for internalized stigmatization may have positive effects on the internalized stigmatization levels of patients with bipolar disorder.

Paleoamerican exploitation of extinct megafauna revealed through immunological blood residue and microwear analysis, North and South Carolina, USA.

Previous immunological studies in the eastern USA have failed to establish a direct connection between Paleoamericans and extinct megafauna species. The lack of physical evidence for the presence of extinct megafauna begs the question, did early Paleoamericans regularly hunt or scavenge these animals, or were some megafauna already extinct? In this study of 120 Paleoamerican stone tools from across North and South Carolina, we investigate this question using crossover immunoelectrophoresis (CIEP). We find immunological support for the exploitation of extant and extinct megafauna, including Proboscidea, Equidae, and Bovidae (possibly Bison antiquus), on Clovis points and scrapers, as well as possible early Paleoamerican Haw River points. Post-Clovis points tested positive for Equidae and Bovidae but not Proboscidea. Microwear results are consistent with projectile usage, butchery, fresh- and dry hide scraping, the use of ochre-coated dry hides for hafting, and dry hide sheath wear. This study represents the first direct evidence of the exploitation of extinct megafauna by Clovis and other Paleoamerican cultures in the Carolinas and more broadly, across the eastern United States, where there is generally poor to non-existent faunal preservation. Future CIEP analysis of stone tools may provide evidence on the timing and demography of megafaunal collapse leading to eventual extinction.

An evidence-based approach to assessing the effectiveness of training regimen on athlete performance: Youth soccer as a case study.

Athletic performance data are modeled in an effort to better understand the relationship between both hours spent training and a measurement of "commitment" to that training, and improvements in performance. Both increased training time and greater commitment were predicted to produce larger increases in performance improvement, and commitment was predicted to be the more important determinant of improvement. The performance of 108 soccer players (ages 9-18) was quantified over a 10-week training program. Hours spent training ranged from 16 to 90 during the course of the study, while commitment scores ranged from 0.55 to 2.00, based on a scale from 0.00 to 2.40. A model selection approach was used to discriminate among models specifying relationships between training hours and improvement, and commitment and improvement. Despite considerable variability in the data, results provided strong evidence for an increase in performance improvement with both training hours and commitment score. The best models for hours and commitment were directly compared by computing an evidence ratio of 5799, indicating much stronger evidence favoring the model based on commitment. Results of analyses such as these go beyond anecdotal experience in an effort to establish a formal evidentiary basis for athletic training programs.

Genetic diversity and relationship among indigenous Turkish Karayaka sheep subpopulations.

The Karayaka is the most populous sheep breed in the Black Sea region of Turkey. In the present study, we investigated the intra- and inter-population genetic relationships among indigenous Karayaka sheep subpopulations. Nine microsatellites were genotyped for 64 individuals from Samsun, Ordu, Giresun and Tokat provinces. The average number of alleles ( N a ), allelic richness ( A r ), observed heterozygosity ( H o ), expected heterozygosity ( H e ), polymorphism information content (PIC) and inbreeding coefficient ( F IS ) for all subpopulations were estimated as N a = 16.44 , A r = 9.887 , H o = 0.303 , H e = 0.886 , PIC = 0.866 and F IS = 0.630 , respectively. The observed and expected heterozygosity ranged from 0.171 (Giresun) to 0.376 (Ordu) and 0.757 (Samsun) to 0.845 (Ordu), respectively. It was determined that a 10.5 % of total genetic variation ( F IT = 66.9  %) in Karayaka sheep corresponded to genetic differences among subpopulations ( F ST ), whereas 63.0 % was explained by genetic difference among individuals ( F IS ). This study gives the first evidence about genetic relationships of Karayaka subpopulations. The results show that Karayaka sheep subpopulations are genetically different from each other. These findings revealed that the Karayaka breed has discrete subpopulations and should be taken into consideration when preparing conservation programs and future breeding strategies.

Alterations in semen parameters of toll collectors working at motorways: does diesel exposure induce detrimental effects on semen?

Air pollution is contemporarily considered to be a significant cause in impairing semen parameters. The aim of this study was to investigate possible effects of traffic pollutants, mainly the diesel exposure, on semen analysis. A total of 38 men working as toll collectors at motorways formed the study group. Simultaneously, 35 men working as office personnel constituted the control group. Factors including varicocele, chronic diseases that can affect sperm production were the exclusion criteria. No difference regarding smoking was present between the groups. Usual semen analysis according to WHO guidelines was performed. The results of semen analysis revealed decreased motility and low sperm counts in eight and seven men from the study group respectively. Besides, a man from the same group had combined abnormality of decreased motility and low sperm count. However, two men from the control group had slight motility defect and one had low sperm count. The differences regarding the abnormal sperm count and motility were significant between the groups (P = 0.002 and P = 0.003, respectively). Similarly, the ratio of sperm cells with normal morphology was significantly lower in the study group than that in the control group (P = 0.001). This observation proposes that air pollution particularly diesel exposure may have detrimental effects on sperm parameters.

Comparison of letrozole and clomiphene citrate in women with polycystic ovaries undergoing ovarian stimulation.

Letrozole was compared with clomiphene citrate (CC) as a first-line treatment for ovulation induction in women with polycystic ovaries (PCOs). A total of 106 women with primary infertility and a diagnosis of PCOs were randomized to receive either 100 mg CC (n = 55) or 2.5 mg letrozole (n = 51) daily for 5 days. Human chorionic gonadotrophin (hCG) at a dose of 10000 IU was administered when at least one follicle with a mean diameter > or = 18 mm was observed using transvaginal ultrasound. The number of mature follicles was significantly lower, but endometrial thickness and ovulation and pregnancy rates were significantly higher in the letrozole group than in the CC group. In conclusion, letrozole is associated with a higher pregnancy rate than CC in PCO patients and may have a role as a first-line treatment for anovulatory patients with PCOs.

Differential effects of streptozotocin-induced diabetes on cardiac lipoprotein lipase activity.

Lipoprotein lipase (LPL) is an endothelial-bound enzyme that is rate determining for the clearance of triacylglycerol-rich lipoproteins. Previous studies using rats with streptozotocin (STZ)-induced diabetes have reported inconsistent effects on cardiac LPL activity or immunoreactive protein. To examine the contribution of the severity and duration of diabetes on cellular and heparin-releasable cardiac LPL activity, Wistar rats were administered a high (100 mg/kg; D100) or moderate (55 mg/kg; D55) dose of STZ, and LPL activity was examined at various times after diabetes induction. Heparin perfusion of the isolated Langendorff control heart induced the release of LPL activity as an initial fast phase followed by a slow phase of release. With increasing age, the second phase of LPL release became more pronounced. Severe STZ-induced diabetes reduced heparin-releasable LPL activity by 1 week in the D100 rats. However, in D55 rat hearts, peak heparin-releasable LPL activity was higher than that in control animals at 2 and 12 weeks after STZ injection, with a complete absence of the delayed phase at 12 weeks. The elevated heparin-releasable LPL peak could not be explained by an enhanced LPL synthesis because both cellular and surface-bound LPL activities in myocytes from D55 rats were low, relative to control. Chronic (12-day) insulin treatment of D55 rats prevented the rise in heparin-releasable LDL and the reduction in cell-associated LPL activity. Moreover, acute (90-min) treatment of D55 rats with rapid-acting insulin also reduced the heparin-releasable LPL activity to normal levels, although it had no effect on the low cellular LPL activity. When the heparin-releasable LPL pool was allowed to recover for 1 h after removal of the enzyme, D55 rat hearts continued to demonstrate a higher peak LPL activity after a second heparin perfusion. These studies demonstrate that in moderate but not severe diabetes, there is an augmented peak heparin-releasable LPL activity. Whether or not this enhanced heparin-releasable LPL activity has a pathological role in the diabetic heart has yet to be determined.

Growth, carcass and meat characteristics of Karayaka growing rams fed sugar beet pulp, partially substituting for grass hay as forage.

Twenty-one growing male Karayaka sheep were divided into three groups of seven at 12 months of age. All groups received a commercial feed (60%) and roughage (40%). One group received grass hay as roughage (control, C), the other two groups received a mixture in which 40 (0.40SBP) or 60% (0.60SBP) sugar beet pulp (SBP) was used in partial replacement of grass hay in the C group during 56 days. Dry matter (DM) intake and DM conversion index (kg DM per kg weight gain) of the C group were higher (P<0.01) than that of the 0.40SBP and 0.60SBP groups. While the 0.60SBP increased (P<0.05) the L* of meat from the Karayaka young rams, the 0.40SBP or 0.60SBP decreased the ultimate pH (P<0.05) and cooking loss (P<0.01) compared to the C group. Means for redness (a*), yellowness (b*), Hue (H*) and Chroma (C*) and sensory characteristics indicated that there were no significant differences between dietary treatments. Inclusion of 60% SBP increased the palmitic (P<0.02) and linoleic (P<0.01) acid contents of the meat, it decreased (P<0.01) stearic, oleic and arachidonic acid contents compared to the C group. The 0.40SBP also increased (P<0.01) the linoleic acid content of the meat, but it decreased (P<0.01) stearic and arachidonic acid contents compared to the control. Although meat from young rams fed 0.60SBP diet had a higher value of lightness and linoleic acid, and a lower value of cooking loss than those from animals fed the C diet, sensory evaluation did not discriminate the meat from young rams fed with control and/or SBP diets. Therefore, grass hay can be replaced by 60% of SBP in the growing diet for Karayaka rams without a reduction in meat quality.

Cardiac lipoprotein lipase in the spontaneously hypertensive rat.

OBJECTIVE: The objectives of the present study were to determine functional (i.e., heparin-releasable) and intracellular (i.e., heparin-non-releasable) cardiac lipoprotein lipase (LPL) activity during the development of hypertension in spontaneously hypertensive (SHR) rats. METHODS: Male WKY and SHR rats were killed before (7-8 weeks of age) and following (15-16 weeks of age) the development of severe hypertension in SHR rats. LPL activity in coronary perfusates was determined by retrogradely perfusing the hearts with heparin (5 U/ml). Cardiac myocytes were also isolated from the two groups of rats by collagenase digestion, and surface-bound and intracellular LPL activity measured. RESULTS: With the development of hypertension in SHR rats, there was a concomitant and progressive reduction in the heparin-releasable coronary endothelial LPL activity. Neither insulin action nor cell-associated enzyme activity could explain this low LPL activity in coronary blood vessels. However, acute vasodilation with nifedipine (a Ca2+ influx blocker) or CGS-21680 (A2-purinergic receptor agonist) increased the peak heparin-releasable LPL activity in hearts isolated from SHR rats. CONCLUSIONS: Our results indicate that hypertension per se may play a significant role in regulating cardiac LPL activity, and hence fatty acid supply to the hypertensive SHR rat heart.

Strain differences in susceptibility to streptozotocin-induced diabetes: effects on hypertriglyceridemia and cardiomyopathy.

OBJECTIVE: Streptozotocin (STZ)-induced diabetes in Wistar rats results in severe hyperlipidemia and a characteristic cardiomyopathy. However, Wistar-Kyoto (WKY) rats made diabetic with a similar dose of STZ did not develop heart dysfunction or hypertriglyceridemia at 12 weeks post-STZ. We investigated whether an apparent resistance of the WKY strain to develop diabetic cardiomyopathy and hypertriglyceridemia following chronic diabetes could be due to a reduced susceptibility to the diabetogenic effects of STZ. METHODS: Adult male WKY and Wistar rats were made diabetic with a moderate (55 mg/kg) or high (75 mg/kg) dose of STZ. At 6 weeks of diabetes, glucose tolerance, cardiac function, pancreatic insulin content and basal and post-heparin plasma lipolytic activity were determined. RESULTS: Administration of a moderate dose of STZ produced cardiac dysfunction in Wistar but not WKY rats at 6 weeks after diabetes induction. The same dose of STZ in WKY rats also resulted in a lesser degree of hyperglycemia and glucose intolerance, and significantly higher pancreatic insulin content relative to Wistar rats. Following a high dose of STZ, the apparent resistance to developing cardiomyopathy was lost in the WKY rats. As well, the WKY rats demonstrated an equal degree of hyperglycemia and glucose intolerance as Wistar rats. However, unlike the Wistar strain, WKY rats did not demonstrate either hypertriglyceridemia or a reduced heparin-releasable plasma lipoprotein lipase (LPL) activity following a high dose of STZ. CONCLUSIONS: These results suggest that the incidence of diabetes-related cardiomyopathy and hypertriglyceridemia in rats may be independently influenced by strain-dependent susceptibilities to the beta-cytotoxic effects of STZ. The absence of hypertriglyceridemia in severely diabetic WKY rats may be linked to the maintenance of a critical level of plasma LPL activity.

Streptozotocin-induced diabetes enhances cardiac heparin-releasable lipoprotein lipase activity in spontaneously hypertensive rats.

Vascular endothelial-bound lipoprotein lipase (LPL), also known as heparin-releasable LPL, catalyzes the breakdown of the triglyceride component of lipoproteins and is rate-limiting for free fatty acid transport to tissues. We previously demonstrated that heparin-releasable LPL activity increases in diabetic Wistar rat hearts, whereas with the development of hypertension in spontaneously hypertensive rats (SHR), there is a concomitant and progressive reduction in LPL activity. The objective of the present study was to examine the regulation of cardiac LPL activity in SHR-diabetic rats. Heparin perfusion of the isolated Langendorff heart induced the release of LPL activity. SHR hearts demonstrated a reduction in peak heparin-releasable LPL activity, relative to Wistar controls. However, induction of streptozotocin-induced diabetes in SHR, as in Wistar rats, increased peak heparin-releasable LPL activity in perfused hearts. The elevated heparin-releasable LPL peak could not be accounted for by enhanced LPL synthesis in that both cellular and surface-bound LPL activities in myocytes from SHR-diabetic rats were low relative to control. Chronic (12-day) insulin treatment of SHR-diabetic rats reduced the augmented heparin-releasable LPL activity and increased cell-associated LPL activity. Moreover, acute (90-minute) treatment of SHR-diabetic rats with rapid-acting insulin also reduced the heparin-releasable LPL activity to normal, although it had no effect on the low cellular LPL activity. These results demonstrate that the diabetes-induced augmentation of cardiac LPL counteracts the reduction in enzyme activity associated with hypertension. This may serve to increase the delivery of free fatty acid to the heart, and the resultant metabolic changes may lead to the severe cardiomyopathy observed in the hypertensive-diabetic rat heart.

Distinct glucose lowering and beta cell protective effects of vanadium and food restriction in streptozotocin-diabetes.

Vanadium is an oral insulin-mimetic agent that diminishes hyperglycemia, improves beta-cell insulin store and secretory function, and can reverse the diabetic state chronically after withdrawal from treatment. As food restriction has been reported to enhance insulin sensitivity and reduce insulin demand, we assessed the contribution of a reduced food intake to the glucose lowering and beta-cell protective effects of vanadium. Streptozotocin (STZ)-diabetic rats were untreated (D) or administered vanadyl sulfate in the drinking water (DT) at one week prior to and for 5 weeks following the administration of STZ. An additional group was pair-fed (DP) with an equal amount of food as that consumed by the DT group. Shortly after the induction of diabetes, hyperglycemic D rats demonstrated a significant rise in plasma insulin to levels that initially exceeded that of the controls. This was followed by a steady reduction over several weeks, suggesting a gradual depletion of functional beta-cells. Both vanadium treatment and pair-feeding abolished the insulin hypersecretory response following STZ administration. Glucose lowering was enhanced in DT animals when administered higher concentrations of vanadium, despite no further reduction in food intake, and all DT animals (10/10) were normoglycemic by 5 weeks. Mean pancreatic insulin content in DT rats was improved fourfold and was associated with a greater number of granulated beta-cells. Conversely, food restriction only modestly improved glycemia and the pancreatic insulin store and, unlike DT, DP rats remained highly glucose-intolerant. At 5 weeks of diabetes, fed circulating glucose and insulin levels were strongly correlated (P=0.0002) in the D and DP groups, supporting the notion that glucose lowering with food restriction is dependent on improved plasma insulin levels. A separate correlation was observed in DT animals within a lower range of plasma insulin, suggesting that vanadium, unlike food restriction, reduced plasma glucose by enhancing insulin sensitivity. Thus, vanadium preserves beta-cells in STZ-diabetes at least partially by abolishing the insulin hypersecretory response and the eventual exhaustion of residual insulin stores following a moderate dose of STZ. This property of vanadium would appear to be useful in the treatment of prediabetic and newly diagnosed insulin-dependent diabetes mellitus.

Concentration-dependent glucose-lowering effects of oral vanadyl are maintained following treatment withdrawal in streptozotocin-diabetic rats.

We have recently reported that treatment with vanadyl sulfate 0.75 mg/mL in drinking water eliminates hyperglycemia in a subset of streptozotocin (STZ)-diabetic rats, with some rats remaining unresponsive to such treatment. In the present study, we demonstrate that unresponsive diabetic animals become normoglycemic when given higher concentrations of vanadyl. Since the subset of rats that require higher concentrations ([HC] 1.25 to 1.50 mg/mL) were found to be more severely diabetic before treatment than those that responded to lower concentrations ([LC] 0.75 to 1.00 mg/mL), the relative amount of residual circulating insulin (LC 36.0 +/- 2.2 v HC 25.6 +/- 3.3 microU/mL) appeared to be a key element in achievement of a normoglycemic effect to a given dose of vanadyl. Similarly, STZ-diabetic animals that responded to euglycemia with a more potent organic vanadyl compound (naglivan) had higher pretreatment plasma insulin levels than unresponsive animals (DT-R) (35.5 +/- 1.9 v 24.2 +/- 3.6 microU/mL). Vanadyl treatment over 10 weeks resulted in a period of normalized glucose levels and glucose tolerance after treatment was stopped. At 20 weeks after withdrawal from treatment with vanadyl sulfate, 13 of 19 animals remained euglycemic, whereas four of seven naglivan-treated animals also maintained normal glucose levels after a 30-week withdrawal period. At 3 weeks after withdrawal, maintenance of normal glucose homeostasis appeared to be independent of altered insulin levels, whereas at 20 weeks an improved insulin secretion, albeit 50% that of age-matched controls both in the fed state and in response to a glucose dose, was sufficient to return plasma glucose levels to the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Lack of in vivo effect of vanadium on GLUT4 translocation in white adipose tissue of streptozotocin-diabetic rats.

Vanadium treatment, in vivo, corrects the severe hyperglycemia observed in streptozotocin (STZ)-diabetic rats. A number of metabolic effects of vanadium have been demonstrated in vitro and might contribute importantly to normalization of glucose homeostasis. However, many in vitro effects of vanadium occur at concentrations substantially higher than those achieved in vivo. Effects of vanadium on white adipose tissue have been particularly well characterized in vitro. To examine the relationship between in vitro and in vivo actions of vanadium, we examined the effects of vanadium treatment on acute glucose tolerance and adipose tissue GLUT4 control in vivo. In agreement with previous studies, vanadium treatment of STZ-diabetic rats restored normoglycemia with no appreciable restoration of insulin secretion. GLUT4 expression in white adipose tissue was reduced by 22% in STZ-diabetic rats compared with controls. Vanadium treatment did not significantly alter GLUT4 expression in controls, but completely restored normal expression levels in STZ-diabetic rats. In overnight-fasted control animals, GLUT4 translocation to the plasma membrane (PM) was maximally elevated (by 50%) in adipose tissue within 5 to 10 minutes after an intravenous (IV) glucose challenge. No glucose-induced translocation of GLUT4 was detected in diabetic rats, and peak PM GLUT4 content was 40% lower than in controls. Vanadium treatment did not increase peak PM GLUT4 content in either control or diabetic animals in response to a glucose load. Finally, the suppression of whole-body acute glucose tolerance in diabetic animals was only partially normalized by vanadium treatment. We conclude: (1) that concentrations of vanadium effective for maintaining normoglycemia in vivo (typically below 30 micromol/L) promote normal GLUT4 expression, but do not influence the subcellular localization of GLUT4 in white adipose tissue and (2) that in vivo effects of vanadium may not necessarily reflect the actions observed in vitro at supraphysiologic concentrations.

Partial preservation of pancreatic beta-cells by vanadium: evidence for long-term amelioration of diabetes.

Streptozotocin (STZ)-diabetic rats treated with vanadium can remain euglycemic for up to 20 weeks following withdrawal from vanadium treatment. In this study, we examined the effects of short-term vanadium treatment in preventing or reversing the STZ-induced diabetic state. Male Wistar rats were untreated (D) or treated (DT) with vanadyl sulfate for 1 week before administering STZ. Treatment was subsequently maintained for 3 days (DT3) or 14 days (DT14) post-STZ, after which vanadium was withdrawn. At 4 to 5 weeks post-STZ and following long-term withdrawal from vanadium, DT14 rats demonstrated levels of food and fluid intake and glucose tolerance that were not significantly different from those of age-matched untreated nondiabetic rats, and had significantly reduced glycemic levels in the fed state compared with D and DT3 groups. The proportion of animals that were euglycemic (fed plasma glucose < 9.0 mmol/L) was significant in DT14 (five of 10) relative to D (one of 10) and DT3 (one of 10) (P = .01). All euglycemic animals had an improved pancreatic insulin content that, albeit low (12% of control), was strongly linked to euglycemia in the fed state (r = -.91, P < .0001). Moreover, the highly significant correlation persisted with the analysis of untreated STZ-rats alone (r = -.95, P < .0001). Similarly, improvements in glucose tolerance and insulin secretory function in euglycemic rats were strongly correlated with small changes in residual insulin content. Hence, as vanadium pretreatment did not prevent STZ-induced beta-cytotoxicity, the vanadium-induced amelioration of the diabetic state appears to be secondary to the preservation of a functional portion of pancreatic beta cells that initially survived STZ toxicity. The partial preservation of pancreatic beta cells, albeit small in proportion to the total insulin store, was both critical and sufficient for a long-term reversal of the diabetic state. These results suggest that apparently modest effects in preserving residual pancreatic insulin content can have profound consequences on glucose homeostasis and may bear important implications for interventions that have "limited" protective effects on beta cells.

A sensitive radioimmunoassay optimized for reproducible measurement of rat plasma insulin.

There has been a notable lack of consistency in plasma insulin values reported in the literature. In an attempt to find a more reproducible and sensitive insulin radioimmunoassay (RIA) method for the measurement of plasma insulin, the charcoal adsorption method for separation of free from antibody-bound antigen was investigated. The applicability of this method towards the measurement of plasma insulin, however, has been known to be severely limited because of interference by plasma proteins with charcoal binding. Indeed, the assay resulted in negative fasting insulin values and unacceptable interassay variability, which was not improved by adding charcoal-extracted plasma (CEP) to the standard curve. In this paper, we demonstrate a process by which relatively small volumes (25 microL) of plasma from control, diabetic, and fasted rats can be assayed reproducibly with charcoal in the final separation step. It was observed that the assay of insulin-free plasma, in the form of CEP, could represent a distinct "zero insulin" level specific for plasma samples, in place of the zero insulin standard (insulin-free standard buffer) routinely used. Normalizing plasma samples against CEP resulted in lower intra-assay and interassay variability (coefficient of variation < 10%) and enhanced sensitivity to 7 microU/mL. Recovery was tested by adding 25 microL of known insulin standards to plasma samples in which insulin levels had been determined previously. Whereas the recovery of total insulin in the presence of plasma was low (38%-89%), recovery of total insulin from two standards was > 95%. Following correction, recovery of total insulin in 25-microL plasma was improved to > 90%. Hence, this approach provides a simplified way of correcting for plasma effects and greatly enhances the feasibility of using the charcoal-separation technique for the measurement of plasma insulin.

In vivo antidiabetic actions of naglivan, an organic vanadyl compound in streptozotocin-induced diabetes.

The vanadyl (+IV) form of vanadium has been demonstrated to have insulin-mimetic activity in vivo. In an effort to improve the poor gastrointestinal absorption of the ion, an organic complex of vanadyl (naglivan) was synthesized. We tested the antidiabetic effects of naglivan in rats made diabetic with streptozotocin (55 mg/kg, i.v.). Four days after the streptozotocin injection, one diabetic group (DVI) and a control group (CV) were treated with naglivan (50 mg/kg/day, equivalent to 0.06 mmol vanadium/kg/day) by oral gavage. Treatment in the DVI group was supplemented with daily insulin while a second diabetic group (DI) was administered daily titrated doses of insulin alone (Protamine Zinc, s.c.) to achieve stable euglycemia. The dose of exogenous insulin required to maintain normal glucose was significantly lower in the DVI group compared to the DI throughout the treatment period. At the end of week 3, exogenous insulin was withdrawn from both the DVI and DI groups, while naglivan treatment was continued in the CV and DVI groups for an additional 5 weeks. At termination, hearts were isolated and cardiac function (+dP/dt, -dP/dt and left ventricular developed pressure) was assessed in all the animals. After insulin was withdrawn, 4/8 DVI animals which continued to receive naglivan had consistent normoglycemia (as determined by % glycosylated hemoglobin) and an improved cardiac function. All the DI animals and 4/8 DVI rats were hyperglycemic and had depressed heart function despite having similar plasma insulin levels to the euglycemic DVI animals. As with vanadyl sulfate, there were no signs of long-term toxicity with regards to renal or liver function after 8 weeks of treatment. Thus, naglivan is an orally effective form of vanadyl with an oral potency 7.6 times greater than that of vanadyl sulfate (minimum effective dose: 0.06 mmol vanadium.kg-1.day-1) as compared to vanadyl sulfate (0.46 mmol vanadium.kg-1.day-1). The lack of incidence of diarrhea in either control or diabetic animals demonstrates that naglivan could be a more therapeutically desirable form of vanadyl.

[Atrial myxoma: cutaneous manifestations]. / Myxome de l'oreillette: manifestations cutanées.

INTRODUCTION: Atrial myxomas may have variable misleading symptoms, explaining frequent delays in diagnosis. Multiple embolisms with irreversible consequences may occur. The dermatologist has a prominent role to play, as the clinical picture includes cutaneous signs. CASE REPORT: A 60 year old woman, with previous history of joint pain and Raynaud's phenomenon suffered a sudden neurological transitory ischemic event. The cutaneous manifestations associated left forearm erythematous macules, distal ischemia of the left fourth and fifth fingers and livedo of both lower limbs. Cardiac echography confirmed the clinical diagnosis of atrial myxoma. Surgical excision was followed by rapid and complete cure. DISCUSSION: Atrial myxoma is a rare benign tumor usually revealed by prominent cardiac and embolic manifestations. Systemic and cutaneous signs may however be the sole symptoms, warranting the dermatologist's attention.

[Acute mast cell leukemia disclosed by vasomotor flushing]. / Leucémie aiguë à mastoblastes révélée par des bouffées vasomotrices.

INTRODUCTION: Acute mast cell leukemia is a rare and severe disease. We report herein a case associated with a flush syndrome. CASE REPORT: A 44-year-old man, presented with a flush of face and trunk. Bone marrow was infiltrated with immature mast cells. In spite of chemotherapy and bone marrow transplantation the patient deceased. DISCUSSION: Pheochromocytoma, carcinoid tumor, and mastocytosis are associated with a flush syndrome. In our patient the diagnosis was an acute mast cell leukemia. Acute mast cell leukemia can follow systemic mastocytosis or occur de novo. This disease is of poor prognosis. No treatment is available.