Response of adipose tissue lipoprotein lipase to the cephalic phase of insulin secretion. (1/1771)

Modulation of lipoprotein lipase (LPL) allows a tissue-specific partitioning of triglyceride-derived fatty acids, and insulin is a major modulator of its activity. The present studies were aimed to assess in rats the contribution of insulin to the response of adipose tissue and muscle LPL to food intake. Epididymal and retroperitoneal adipose LPL rose 65% above fasting values as early as 1 h after the onset of a 30-min high-carbohydrate meal, with a second activity peak 1 h later that was maintained for an additional 2 h. Soleus muscle LPL was decreased by 25% between 0.5 and 4 h after meal intake. The essential contribution of insulin to the LPL response to food intake was determined by preventing the full insulin response to meal intake by administration of diazoxide (150 mg/kg body wt, in the meal). The usual postprandial changes in adipose and muscle LPL did not occur in the absence of an increase in insulinemia. However, the early (60 min) increase in adipose tissue LPL was not prevented by the drug, likely because of the maintenance of the early centrally mediated phase of insulin secretion. In a subsequent study, rats chronically implanted with a gastric cannula were used to demonstrate that the postprandial rise in adipose LPL is independent of nutrient absorption and can be elicited by the cephalic (preabsorptive) phase of insulin secretion. Obese Zucker rats were used because of their strong cephalic insulin response. After an 8-h fast, rats were fed a liquid diet ad libitum (orally, cannula closed), sham fed (orally, cannula opened), or fed directly into the stomach via the cannula during 4 h. Insulinemia increased 10-fold over fasting levels in ad libitum- and intragastric-fed rats and threefold in sham-fed rats. Changes in adipose tissue LPL were proportional to the elevation in plasma insulin levels, demonstrating that the cephalic-mediated rise in insulinemia, in the absence of nutrient absorption, stimulates adipose LPL. These results demonstrate the central role of insulin in the postprandial response of tissue LPL, and they show that cephalically mediated insulin secretion is able to stimulate adipose LPL.  (+info)

Effect of pelvic endometrial implants on overall reproductive functions of female rats. (2/1771)

The effects of pelvic endometrial implants on the overall reproductive potential of female rats were investigated. After homologous transplantation in the peritoneum, the ectopic endometrium developed into highly vascularized nodes that gradually increased in mass until the 9th week postsurgery and then plateaued. In the presence of these implants, overall reproductive function was adversely affected. The effect was of greatest magnitude during 50-70 days posttransplantation. As compared with values in corresponding controls, ovulation was reduced by 43% (6 of 14) (p < 0.05), mating rate was reduced by 44% (12 of 27) (p < 0.025), and premature termination of pregnancy occurred in 34% (5 of 15) of rats. Wastage of pregnancy, which included complete termination or reduction of fetal number, occurred during the postimplantation course of gestation. Furthermore, 100% of the rats with transplants failed to respond to the copulomimetic stimulation for the induction of pseudopregnancy (p < 0.01, compared with corresponding controls). However, on exposure to vasectomized males, 46% (6 of 13) of these rats exhibited development of pseudopregnancy (p < 0.05, compared with corresponding group receiving copulomimetic stimulation). Increased rate of mating failure and differential pseudopregnancy rates after copulomimetic and natural cervical stimulation suggest that the rats with endometrial explants possibly had an absence or a short appearance of behavioral estrus. Hormonal assessment during the preovulatory phase showed a tendency toward lower mean levels of preovulatory estradiol and significantly lower LH (p < 0.01) and progesterone (p < 0.01) concentrations. The adversely affected reproductive functions may be a secondary consequence of these altered endocrine milieus.  (+info)

Severe impairment in early host defense against Candida albicans in mice deficient in myeloperoxidase. (3/1771)

Myeloperoxidase (MPO) catalyzes the reaction of hydrogen peroxide with chloride ion to produce hypochlorous acid (HOCl), which is used for microbial killing by phagocytic cells. Despite the important role of MPO in host defense, however, MPO deficiency is relatively common in humans, and most of these individuals are in good health. To define the in vivo role of MPO, we have generated by gene targeting mice having no MPO activity in their neutrophils and monocytes. The mice without MPO developed normally, were fertile, and showed normal clearance of intraperitoneal Staphylococcus aureus. However, they showed increased susceptibility to pneumonia and death following intratracheal infection with Candida albicans. Furthermore, the lack of MPO significantly enhanced the dissemination of intraperitoneally injected C. albicans into various organs during the first 7 days. Thus, MPO is important for early host defense against fungal infection, and the inability to generate HOCl cannot be compensated for by other oxygen-dependent systems in vivo in mice. The mutant mice serve as a model for studying pulmonary and systemic candidiasis.  (+info)

Effects of interleukin-1 receptor antagonist overexpression on infection by Listeria monocytogenes. (4/1771)

Interleukin-1 receptor antagonist (IL-1ra) is a naturally occurring cytokine whose only known function is the inhibition of interleukin-1 (IL-1). Using a reverse genetic approach in mice, we previously showed that increasing IL-1ra gene dosage leads to reduced survival of a primary listerial infection. In this study, we characterize further the role of endogenously produced IL-1ra and, by inference, IL-1 in murine listeriosis. IL-1ra overexpression inhibits, but does not eliminate, primary immune responses, reducing survival and increasing bacterial loads in the target organs. We demonstrate that IL-1ra functions in the innate immune response to regulate the peak leukocyte levels in the blood, the accumulation of leukocytes at sites of infection, and the activation of macrophages during a primary infection. Reduced macrophage class II major histocompatibility complex expression was observed despite increased gamma interferon (IFN-gamma) levels, suggesting that IL-1 activity is essential along with IFN-gamma for macrophage activation in vivo. We also show that IL-1ra plays a more limited role during secondary listeriosis, blunting the strength of the delayed-type hypersensitivity response to listerial antigen while not significantly altering cellular immunity to a second infectious challenge. When these results are compared to those for other mutant mice, IL-1ra appears to be unique among the cytokines studied to date in its regulation of leukocyte migration during primary listeriosis.  (+info)

Peritoneal clearance of leptin in CAPD patients: impact of local insulin administration. (5/1771)

INTRODUCTION: The ob gene product leptin is secreted by fat cells and the serum leptin levels reflects the body fat content. Markedly elevated serum leptin levels have been reported in patients with chronic renal failure. The aim of the present study was to assess if the dialysate leptin levels in peritoneal dialysate are similar to what can be expected from passive diffusion or if intraperitoneal synthesis of leptin may occur. METHODS: We studied 39 patients (20 males), mean age 54+/-12 years, who had been treated with peritoneal dialysis for 17+/-12 months. Ten of the patients were diabetics of which seven used intraperitoneal insulin. A 24-h collection of dialysate was performed and dialysate and fasting blood samples were analysed for leptin, albumin and beta2-microglobulin, and the peritoneal clearances (PCl) were calculated for these solutes. RESULTS: Serum leptin (mean 47+/-76, range 3-350 ng/ml) was related to body mass index (r=0.35, P<0.05). In multiple regression analysis, serum leptin also correlated to serum TNF-alpha. Although dialysate leptin levels correlated to serum leptin, they were higher than expected from the molecular weight of 16 kD. PCl of leptin was 1.3 ml/min (range 0.2-5.9 ml/min), which was 1.6 times higher than expected from the molecular weight of leptin and PCl for albumin and beta2-microglobulin, not taking the protein binding of leptin into account. A strong correlation was found between PCI for albumin and beta2-microglobulin (r = 0.68, P < 0.0001) but neither PCl albumin, nor PCl beta2-microglobulin correlated to PCI leptin. The PCl of leptin was markedly higher in diabetics using intraperitoneal insulin (n = 7) compared to the other 32 patients (2.6+/-2.0 vs 1.1+/-0.7 ml/min, P<0.05). CONCLUSION: Serum leptin is locally produced in the peritoneal cavity, and intraperitoneal insulin enhances local production of leptin.  (+info)

Does a high peritoneal transport rate reflect a state of chronic inflammation? (6/1771)

OBJECTIVE: It has recently been reported that a high peritoneal transport rate was associated with increased mortality in continuous ambulatory peritoneal dialysis (CAPD) patients. One possible explanation is that a high peritoneal transport rate might be caused by a state of chronic inflammation, which also per se might result in increased mortality. Therefore, in this study we investigated whether high peritoneal transport rate patients are in a state of chronic inflammation. METHODS: The study included 39 clinically stable peritoneal dialysis patients (free of peritonitis) who had been on PD for more than 3 months (16.8+/-11.8 months). Seven patients were treated with continuous cycling peritoneal dialysis (CCPD) and the others were on CAPD. A 4-hour standard peritoneal equilibration test (PET) using 2.27% glucose solution was performed in each patient. Dialysate samples at 4 hours and blood samples at 2 hours were measured for interleukin-1beta (IL-1beta), tumor necrosis factor(alpha)(TNFalpha), C-reactive protein (CRP), and hyaluronan as markers of inflammation. RESULTS: There was no significant correlation between dialysate/plasma (DIP) creatinine (0.82+/-0.15, range 0.51 - 1.15) and blood concentrations of IL-1beta (11.2 ng/L, range <5 - 65.9 ng/L),TNFalpha (12.1 ng/L, range <5 - 85.4 ng/L), CRP (<10 mg/L, range <10 - 76 mg/L), nor with the blood hyaluronan concentration (165 microg/L, range 55 - 955 microg/L). The dialysate concentrations of IL-1beta and TNFalpha were below the detectable level in most of the samples. Although dialysate hyaluronan concentration (334 microg/L, range 89 - 1100 microg/L) was correlated with D/P creatinine (r= 0.36, p< 0.05), there was no correlation between the total amount of hyaluronan in the effluent and D/P creatinine. However, a significant correlation was found between serum hyaluronan concentration and glomerular filtration rate (GFR) (r = -0.49, p< 0.005); GFR also tended to be correlated with serum TNFalpha (r = -0.31, p = 0.058) but not with serum IL-1beta and serum CRP. CONCLUSION: Our results suggest that a high peritoneal transport rate is not necessarily related to a state of chronic inflammation in CAPD patients. The high mortality rate observed in high transporters may relate to other issues, such as fluid balance or abnormal nutrition and metabolism, rather than to chronic inflammation.  (+info)

Tranexamic acid increases peritoneal ultrafiltration volume in patients on CAPD. (7/1771)

OBJECTIVE: The preservation of ultrafiltration (UF) capacity is crucial to maintaining long-term continuous ambulatory peritoneal dialysis (CAPD).The aim of the present study was to investigate whether the antiplasmin agent tranexamic acid (TNA) increases UF volume in CAPD patients. PATIENTS AND METHODS: Fifteen patients on CAPD, 5 with UF loss and 10 without UF loss, were recruited for the study. The effect of TNA was evaluated with respect to changes in UF volume, peritoneal permeability, peritoneal clearance, bradykinin (BK), and tissue plasminogen activator (tPA) concentration. SETTING: Dialysis unit of the Saiseikai Central Hospital. RESULTS: In patients with UF loss, 2 weeks of treatment with oral TNA produced a significant increase in UF volume in all subjects (5/5).TNA also produced a significant increase in peritoneal clearances of urea and creatinine (Cr). However, the peritoneal equilibration test (PET) revealed that TNA had no effect on dialysate/plasma (D/P) Cr, Kt/V, or the protein catabolic rate (PCR).TNA also had no effect on net glucose reabsorption. In contrast, significant decreases in BK and blood tPA concentrations in response to TNA treatment were noted. BK concentration in drainage fluid was also reduced. In the case of patients without UF loss,TNA produced an increase in UF volume in 70% (7/10). However, no differences were found in blood and drainage BK and tPA concentrations between theTNA treatment and nontreatment periods in these patients. A comparison of basal BK and tPA concentration showed that there were no differences in these parameters between patients with UF loss and those without loss of UF. Furthermore,TNA given intraperitoneally to a patient also produced a marked increase in UF volume. CONCLUSION: The present study suggests thatTNA enhances UF volume in patients both with and without UF loss. SinceTNA did not affect peritoneal permeability and glucose reabsorption, the mechanism by which TNA exerts an enhancing action on UF is largely unknown. We speculate that it may be associated with suppression of the BK and/or tPA system, at least in patients with UF loss.  (+info)

Analysis of the peritoneal equilibration test in Mexico and factors influencing the peritoneal transport rate. (8/1771)

OBJECTIVE: To validate the peritoneal equilibration test (PET), establish reference values in the Mexican population, compare our results with those reported by Twardowski et al., and analyze the influence of some factors on the peritoneal transport rate (PTR). DESIGN: Retrospective, cross-sectional study. PATIENTS: Eighty-six PETs were performed in 45 female and 41 male patients; 35 of the patients were diabetics. Creatinine D/P and glucose D/D0 ratios were calculated and compared with those from Twardowski et al. In a multivariate analysis, age, gender, diabetes mellitus (DM), time on dialysis, and peritonitis rate were considered as independent factors influencing the PTR. RESULTS: Creatinine D/P and glucose D/D0 ratios at 4 hours were not significantly different from those reported by Twardowski et al. Creatinine D/P at 4 hours was not different between DM and non-DM patients when the rate of peritonitis and time on dialysis were not taken into account. Multivariate analysis did not result in any significant model predicting the creatinine D/P at 4 hours. CONCLUSIONS: PET validation is reported for the first time in a Latin American population. The PET results of this study are similar to those in the literature. We found that DM, peritonitis rate, time on dialysis, age, and gender did not clearly influence the PTR.  (+info)