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Urinary tumor necrosis factor contributes to sodium retention and renal hypertrophy during diabetes.

Nephropathy is a major contributor to overall morbidity and mortality in diabetic patients. Early renal changes during diabetes include Na retention and renal hypertrophy. Tumor necrosis factor (TNF) is elevated during diabetes and is implicated in the pathogenesis of diabetic nephropathy. We tested the hypothesis that TNF contributes to Na retention and renal hypertrophy during diabetes. Rats with streptozotocin-induced diabetes exhibit increased urinary TNF excretion, Na retention, and renal hypertrophy through the first 20 days of diabetes. Administration of a soluble TNF antagonist (TNFR:Fc) to diabetic rats reduces urinary TNF excretion and prevents Na retention and renal hypertrophy. TNF stimulates Na uptake in distal tubule cells isolated from diabetic rats, providing a possible mechanism for TNF-induced Na retention. We conclude that urinary TNF contributes to early diabetic nephropathy and may serve as a valuable diagnostic marker. Furthermore, inhibition of TNF during diabetes may attenuate early pathological changes in diabetic nephropathy.

Albuminuria↗

Sodium retention and ascites formation in dogs with experimental portal cirrhosis.

Experimental cirrhosis was produced in dogs by the sporadic feeding of dimethylnitrosamine for the purpose of studying the temporal relationships between urinary sodium retention, plasma volume expansion, and ascites formation. Sodium retention started about 16 days following the onset of cirrhosis and preceded ascites formation by about 10 days. Plasma volume increased by 9% (P less than 0.05) within 3-4 days of sodium retention and expanded further as ascites accumulated. Splanchnic plasma volume was greater by 161 ml in 10 cirrhotic dogs with ascites than in 14 normal dogs. Nonsplanchnic volume was greater by 96 ml (P less than 0.05). Thus, the "effective" as well as the splanchnic component of the vascular space was expanded. Paracentesis did not cause the re-formation of ascites in five dogs as long as dietary salt was denied. Refeeding permitted reaccumulation of ascites and further plasma volume expansion. Renal perfusion remained constant as dogs became progressively cirrhotic. We conclude that ascites formation depends on the prior retention of urinary sodium, and occurs as an "overflow" phenomenon. A contracted effective plasma volume does not appear to be necessary for continuing sodium retention.

Animals↗

Anesthesia alters the pattern of aerosol retention in hamsters.

General anesthesia was used to produce nonventilated areas of the lung, and aerosol inhalation was used to locate these areas, assuming that no aerosol deposits in a nonventilated region. Male Syrian golden hamsters were anesthetized with pentobarbital sodium (90 mg/kg), which reduced respiratory frequency, tidal volume, minute volume, and O2 consumption to 61, 41, 24, and 36%, respectively, of the corresponding awake levels. Awake and anesthetized hamsters were exposed to the aerosol for 30 min; then the lungs were excised, dried at total lung capacity, sliced into sections, and dissected into pieces. Autoradiographs were made of slices, and the activity and weight of pieces were determined. The evenness index (EI), a measure of the uniformity of retention, was calculated for each piece. With complete uniformity of retention, all EI's would be 1.0. In awake animals, only 0.2% (by wt) of the lungs had little or no retention (EI's less than 0.20). More particles deposited in the apex than in the base of the lungs. General anesthesia for extended periods of time with no deep breaths alters ventilation and therefore the distribution of aerosol retention. Many regions of the lungs in the anesthetized animals received few or no particles (11.6% of lungs had EI less than 0.20); however, no consistent pattern was observed in the location of these areas from animal to animal. The apex-to-base gradient for retention in these animals was also reversed. Radioactive aerosols can be used as probes to indicate the extent and distribution of nonventilated areas in the lungs.

Aerosols↗

Lung water is increased in regions of higher neutrophil retention after acute bead embolization.

Previous reports have shown that neutrophils are retained in the lung after acute embolization and that these neutrophils play an important role in the subsequent formation of permeability pulmonary edema. The present study was designed to test the hypothesis that acute embolic injury results in microvascular damage in lung regions with the greater retention of neutrophils. Seventeen pigs (20 +/- 2 kg) were embolized by injecting polystyrene beads (250 microns; labeled with 131I) into the right atrium over 5 min. Five pigs, which received no embolic beads, served as controls. Neutrophils (89 +/- 5% pure), isolated on Ficoll-Histopaque gradient, were radiolabeled with 111In-oxine. Twenty minutes after embolization, the radiolabeled neutrophils were injected into the right atrium along with 85Sr-labeled microspheres to mark the initial neutrophil distribution within the lung as well as the regional pulmonary blood flow at the time of their delivery. The animals were killed 50 min after embolization, and the lungs were removed, frozen over liquid nitrogen, and cut into 60 samples. The data show that after embolization regional neutrophil retention was inversely related to the regional blood flow but was not affected by the embolic load in the same region. Regional extravascular lung water was increased in regions of higher neutrophil retention, but the regions with increased edema did not receive a greater embolic load. These results show that microvascular injury occurs in the lung regions with the greatest neutrophil retention and that this increased retention of neutrophils is unrelated to the extent of embolization.

Animals↗

Pathogenesis of renal sodium retention in congestive heart failure.

This article summarizes briefly some factors responsible for edema in chronic congestive heart failure. It is now generally thought that so-called 'backward failure' is a manifestation of diastolic dysfunction, while systolic 'pump failure' is a disease that depends on two key factors: an inadequate cardiac output, and renal salt and water retention. The key elements involved in what might be termed the 'integrated volume response' are hemodynamic and renal factors. The hemodynamic factors include vasoconstriction, tachycardia and a reduced venous capacitance. These responses occur within minutes, while salt and water retention occurs over days to weeks. The key renal elements modulating sodium retention in congestive heart failure include, at a minimum, four variables. First, there is a reduction in renal blood flow produced by the almost simultaneous operation of alpha- and beta-catecholamines, antidiuretic hormone, the endothelins, and angiotensin II. Second, activation of the tubuloglomerular feedback system enhances intrarenal angiotensin II release, which augments proximal sodium absorption. In addition, beta-catechols also enhance proximal sodium absorption. A third key element involved in renal sodium retention is activation of apical sodium channels, ENaC, of principal cells in the cortical collecting tubule by aldosterone and by vasopressin. Finally, the inner medullary collecting duct becomes resistant to the action of atrial natriuretic peptide, thus adding a final dimension to the syndrome of sodium retention in underfilling.

Animals↗

Comparison of 75SeHCAT retention half-life and fecal content of individual bile acids in patients with chronic diarrheal disorders.

Measurement of the retention of 23-75Se-25-homotaurocholic acid (SeHCAT) has been suggested as a new test for ileal function. We investigated 31 patients with chronic diarrhea, 10 with ileal Crohn's disease and 21 with diarrhea but without ileal disease. The whole-body retention half-life of 1 mu Ci SeHCAT was determined and compared to the fecal content of total and individual bile acids. Patients with ileal disease had increased primary fecal bile acids (chenodeoxycholic acid: mean 6.95 mg/g dry weight, range 3.15-10.6 mg/g; cholic acid: mean 18.15 mg/g, range 10.3-33.9 mg/g) and a short SeHCAT retention (mean 11.9 h, range 2-24 h), whereas patients with intact ileum had normal fecal bile acids and a SeHCAT retention of 85.9 h (range 28-216 h). SeHCAT retention half-life differentiated well between patients with ileal disease and patients with normal ileum, thus indicating the SeHCAT test as a valid investigation method for detection of primary bile acid malabsorption in patients with chronic diarrhea and ileal dysfunction.

Adolescent↗

Modified in vivo platelet retention test for evaluating primary haemostasis.

We present a modified in vivo platelet retention test for evaluating platelet plug formation in a standardized incision applied to the skin (template bleeding time). In contrast to previously published similar procedures we determined platelet retention at defined time intervals. The investigation of 20 healthy subjects with this method revealed a characteristic biphasic pattern of platelet consumption at the wound surface, which could be correlated with primary and secondary platelet aggregation. In 10 patients with congenital platelet dysfunction and 2 patients with von Willebrand's disease the pattern of platelet retention was affected principally in its early phase, whereas aspirin, when given to 2 healthy subjects, inhibited platelet retention predominantly in its late phase. Our modified platelet retention test provides information about dynamic events associated with platelet plug formation in both normal and disordered primary haemostasis and may also be useful for evaluating in vivo effects of antithrombotic drugs.

Adolescent↗

The role of protonation and conformational transition of polyamine grafts in platelet retention to polyamine-graft-PHEMA copolymer surfaces.

Blood platelet retention on polyamine-graft-poly(2-hydroxyethyl methacrylate) (PHEMA) copolymer (HA) surface was investigated, focusing on pH and ionic strength of the surrounding medium to elucidate the nature of ionic interaction between platelets and HA copolymer surfaces. The conformational transition of polyamine graft chain in response to the protonation degree of amino groups was demonstrated to be an important factor influencing platelet retention on HA surfaces. When the polyamine graft chain exists in an extended conformation, protonated amino groups distribute from the matrix interface into the aqueous interior, resulting in the effective ionic interaction with platelets to increase their retention on HA copolymer surfaces. The number of protonated amino groups in polyamine portions crucially affected platelet retention. Worth noticing is that an introduction of a small but definite amount of cationic sites on the polymer surface led to significantly minimized platelet retention. It is considered that the surface property of PHEMA was drastically changed to a non-adhesive surface by introducing a small amount of protonated amino groups.

Animals↗

Retention of the glycoprotein IIb-IIIa complex in the isolated platelet cytoskeleton. Effects of separable assembly of platelet pseudopodal and contractile cytoskeletons.

To investigate the association of the putative platelet fibrinogen receptor (glycoprotein IIb-III(a) with the cytoskeleton, 125I-surface labeled human platelets washed by gel-filtration were activated under conditions which allow selective assembly of the platelet cytoskeleton. The four conditions were activation with arachidonate or phorbol 12-myristate 13-acetate (PMA) with and without pretreatment with cytochalasin E. Activation with arachidonate generates a complete cytoskeletal core (pseudopodal and contractile elements) while PMA activation forms only an actin plus actin-binding protein pseudopodal core. Pretreatment with cytochalasin E leads to actomyosin contractile core formation if arachidonate activated, and essentially blocks cytoskeletal development if PMA activated. Cytoskeletal cores from arachidonate or PMA-activated platelets retained 26 (+/- 3%) of the total 125I-IIIa. Pretreatment with cytochalasin E followed by arachidonate or PMA activation reduced the 125I-IIIa retention to near control levels (unactivated platelets: 4 +/- 2%). The role of aggregation vs. receptor occupancy in the retention of IIb-IIIa was assessed by activation of platelets with arachidonate in the presence of fibrinogen fragment D (0.6-12 mg/ml). Aggregation was blocked by increasing concentrations of fragment D reagent while cytoskeletal assembly was not altered. The IIIa retention correlated with extent of aggregation with maximal retention corresponding to full aggregation. To determine if cytoskeletal development is necessary for the expression of the fibrinogen binding site, binding studies were performed with unlabeled platelets and 125I-fibrinogen. The mean number of binding sites and the mean dissociation constant were not significantly different among the four activation conditions. Although the development of a platelet cytoskeletal core is not required for the expression of the fibrinogen binding site, the retention of the glycoprotein IIb-IIIa complex is dependent on fibrinogen-supported aggregation as well as the formation of the pseudopodal cytoskeleton.

Arachidonic Acid↗

Ethanol-induced retention of nascent proteins in rat hepatocytes is accompanied by altered distribution of the small GTP-binding protein rab2.

Chronic ethanol consumption induces hepatocellular retention of nascent proteins leading to hepatomegaly. While the molecular mechanisms behind this impairment are undefined, it has been predicted that protein retention results from a disruption of vesicle-mediated secretory processes. Small GTP-binding proteins (rab proteins) have recently been implicated in the regulation of vesicular trafficking in eukaryotic cells. Our objectives were to identify intracellular sites of ethanol-induced protein retention and to determine whether the distribution of secretory rab proteins was altered by ethanol. Transport of hepatic proteins along the secretory pathway in livers from control and ethanol-fed rats was analyzed using subcellular fractionation and immunoprecipitation in the context of in vivo pulse-chase experiments. We show that pre-Golgi and Golgi compartments, as well as secretory vesicles, are sites of ethanol-induced retention of nascent soluble and transmembrane secretory proteins. These results are supported by immunofluorescence localization of hepatic proteins on liver sections. Further, immunoblot analyses of hepatic subcellular fractions from ethanol-damaged livers indicate a dramatic reduction in the association of rab2 with a Golgi compartment as compared with controls. In contrast, rab6 and alpha-mannosidase II, Golgi marker proteins, appear unchanged. These studies provide a detailed analysis of the intracellular site of ethanol-induced protein retention in the hepatocyte and lend novel insight into a potential mechanism behind this impairment. The effects of ethanol exposure on rab proteins and Golgi function are discussed.

Albumins↗

Lack of correlation between food retention on the human dentition and consumer perception of food stickiness.

When dental health professionals advise that sticky foods be avoided, it is left to the consumer to choose correctly among different foods. In this study, comparisons were made among consumer ratings of stickiness of 21 commercially available foods and objective measurements of tooth retention of each of the foods. No correlation was found between the two, and neither the rates of clearance of food particles from the teeth nor the rates of clearance of food-derived sugars from the saliva correlated with ratings of food stickiness. Cookies, crackers, and potato chips were most retentive, whereas caramels, jelly beans, raisins, and milk chocolate bars were among those poorly retained. Clearance rates appeared to vary inversely with initial retention. However, chocolate-caramel bars exhibited high initial retention and a very rapid rate of clearance from the teeth. The findings show that consumers cannot accurately assess the retentiveness of foods and, thus, the advise simply to avoid sticky ones is inadequate.

Adhesiveness↗

Induced hypoxia in rat pulp and periapex demonstrated by 3H-misonidazole retention.

Cellular hypoxia may be a useful indication of tissue distress in the dental pulp that could be used to investigate the early stages of pulpal responses. Tritiated misonidazole (3H-MISO) is a marker which preferentially labels cells with decreased oxygen tension (hypoxia). The experiments reported here were carried out to determine whether this agent could distinguish between hypoxic and normoxic pulp and periapical tissues. Rats were injected intra-peritoneally with either 3H-MISO, unlabeled MISO, or saline, then divided into normoxic, hypoxic, and control groups. Normoxic animals were maintained at ambient pressure. We induced hypoxia by maintaining animals in a hypobaric chamber at 0.5 atm for 24 hrs. 3H-MISO retention was assessed by quantitative analysis of tissue autoradiographs. 3H-MISO retention rates in normoxic animals showed little variation except for increased retention in mature ameloblasts and immature odontoblasts in the continually erupting incisor. In both incisor and molar pulps, hypobaric hypoxia significantly increased 3H-MISO retention when compared with normoxic controls. Hypobaric hypoxia also resulted in intense 3H-MISO retention in cellular cementum, periodontal ligament, osteocytes, and, occasionally, in molar pulp horn odontoblasts. This study demonstrated that, with standard autoradiographic techniques, 3H-MISO can label induced hypoxic disturbances in the pulp and surrounding periodontium.

Ameloblasts↗

Pharmacokinetics of metformin gastric-retentive tablets in healthy volunteers.

The single-dose pharmacokinetics of two gastric-retentive, extended-release tablet formulations of metformin hydrochloride in fed, healthy volunteers were compared with those of the currently marketed immediate-release metformin hydrochloride product. The plasma concentration-time profiles demonstrated extended-release characteristics from the gastric-retentive tablets. The mean bioavailability from each gastric-retentive tablet was approximately 115%, relative to the immediate-release (IR) product. Cmax values were lower and tmax values were greater for the gastric-retentive tablets compared with the IR product. In contrast to conventional extended-release metformin tablets reported in the literature, these gastric-retentive tablets showed extended-release plasma concentration profiles of metformin hydrochloride and increased bioavailability compared with the immediate-release tablet.

Adult↗

Manager leadership and retention of hospital staff nurses.

This study used causal modeling to trace the effects of manager leadership characteristics on staff registered nurse (RN) retention in 4 urban hospitals. Unique to the study were the all-RN sample, using Leavitt's (1958) model of behavior within an organization to group variables, manager characteristics and unit structure variables as predictors, and focus on the work unit rather than the hospital. Effects of manager characteristics were traced to retention through work characteristics, job stress, job satisfaction, commitment, and intent to stay. Theoretical variables explained 22% of the retention variance. Manager consideration of staff and RN intent to remain directly affected retention; other variable effects passed through intent to stay. Different predictors were important to retention, unit separation, and turnover.

Adult↗

Retention in a breast cancer risk information trial: motivations of a population-based sample of women.

A better understanding of factors influencing retention in breast cancer risk education and prevention programs can improve the design and effectiveness of such programs. Such information may also be useful to researchers seeking to maximize full retention in research trials involving low risk and low perceived benefit by the participants. These data are from a population-based study of 481 women from the Seattle, Washington, area, with diverse levels of breast cancer risk. This study sought to describe motivations for retention, to relate motivation variables to demographic characteristics, and to evaluate predictors of retention. Increasing age predicted study assessment completion, and both cancer worry and White ethnicity predicted intervention retention.

Adolescent↗

Post-retention crowding and incisor irregularity: a long-term follow-up evaluation of stability and relapse.

The aim of the present long-term follow-up study of orthodontically-treated patients (mean: 15.7 years) was to analyse post-retention changes and to reveal factors which may play a role as predictors for long-term prognosis. Pretreatment, end-of-treatment, and post-retention models of 226 cases with all types of anomaly were used to measure intercanine and intermolar width, arch length, and sum of the mesiodistal dimension of the incisors, Irregularity Index, crowding, molar and canine relationship, overjet, and overbite. In order to assess the influence of sex, initial and end-of-treatment alignment, type of therapy, amount of tooth movement, and presence of third molars on the extent of post-retention changes, the total sample was divided into subgroups. Findings indicated that post-retention crowding and incisor irregularity increased more frequently in the mandible than in the maxilla. Pretreatment variables such as increased mesiodistal incisor dimension, severe crowding and incisor irregularity, arch length deficiency, arch constriction, and increased overbite as well as post-treatment spacing, arch expansion, increased arch length, and residual Class II or III molar relationships were found to be associated factors in the process of post-retention increase of crowding and incisor irregularity. 'Overexpansion' was found to be a factor in mandibular incisor relapse.

Analysis of Variance↗

Liposome retention in size exclusion chromatography.

BACKGROUND: Size exclusion chromatography is the method of choice for separating free from liposome-encapsulated molecules. However, if the column is not presaturated with lipids this type of chromatography causes a significant loss of lipid material. To date, the mechanism of lipid retention is poorly understood. It has been speculated that lipid binds to the column material or the entire liposome is entrapped inside the void. RESULTS: Here we show that intact liposomes and their contents are retained in the exclusion gel. Retention depends on the pore size, the smaller the pores, the higher the retention. Retained liposomes are not tightly fixed to the beads and are slowly released from the gels upon direct or inverted eluent flow, long washing steps or column repacking. Further addition of free liposomes leads to the elution of part of the gel-trapped liposomes, showing that the retention is transitory. Trapping reversibility should be related to a mechanism of partitioning of the liposomes between the stationary phase, water-swelled polymeric gel, and the mobile aqueous phase. CONCLUSION: Retention of liposomes by size exclusion gels is a dynamic and reversible process, which should be accounted for to control lipid loss and sample contamination during chromatography.

Acetylcholinesterase↗

Nuclear binding and retention of the receptor estrogen complex: relation to the agonistic and antagonistic properties of estriol.

The relationship between nuclear retention or residency or receptor estrogen complexes and the agonistic and antagonistic properties of estriol was examined. Cytoplasmic estrogen receptor (Rc) and uterine weight were measured 24 and 48 h after treatment with estradiol (E2), estriol (E3), or or both hormones (E2 and E3). Levels of Rc were elevated in all groups at either time. Since levels of Rc were above control in each case, Rc does not appear to be the limiting factor in the antagonistic effect of estriol. Therefore, the effect of these steroids on translocation and retention of nuclear receptor estrogen complexes (RnE) was examined. Rats were injectd as above and RnE measured by 3[H] estradiol exchange 1, 3, and 6 h after injection. All treatments cause equal translocation of receptor of the nuclear compartment. However, by 6 h the quantity of Rn present in E2 treated animals was significantly above controls while that in E2 + E3 animals was intermediate. E3 alone failed to cause significant nuclear retention of Rn. These patterns of retention correlate with the weight and cytoplasmic receptor responses above and suggest that the short nuclear residency time of RnE3 complexes relates to the antagonism of E3. To test this, these estrogens were administered via paraffin pellets to maintain blood levels of each hormone. Levels of Rn were elevated 24 and 48 h after implant with no significant differences between treatment groups. Likewise, there were no differences in the growth response. Uterine weights were highly stimulated in all three cases (300% above control). These results indicate that E3 acts as an estrogen antagonist when injected as a bolus because of the short nuclear retention time of RnE3 complexes. However, when E3 is present continuously and RnE3 is elevated and maintained, E3 is a potent estrogen without antagonistic properties.

Animals↗