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At least 883 records · Page 49Linked to original sources
PubMed1988

Respiratory physical therapy in the treatment of chronic bronchitis.

Currently recommended respiratory physical therapy procedures include measures designed to improve the clearance of secretions from the lungs, improve distribution of inspired air, and improve the general physical condition. In patients with chronic bronchitis there is frequently an abundance of thick, tenacious bronchial secretions associated with defective mucociliary function due to diffuse disease of the airways. Those who are unable to clear their secretions adequately are candidates for one or more of the techniques discussed here. In designing a treatment plan for the chronic bronchitic, it is important to use only those techniques with demonstrated benefit and minimal hazard in that particular patient.

Breathing Exercises↗
PubMed1995

[Hypoglycemia--occurrence, causes and hormonal counterregulatory mechanisms in healthy persons and in patients with IDDM].

The occurrence of hypoglycemia is common in patients with insulin-dependent diabetes mellitus. They experience an average of one to two episodes of symptomatic hypoglycemia per week; 10-20% suffer at least one episode of severe hypoglycemia in a given year. The incidence of severe hypoglycemia in diabetic patients treated with intensive insulin therapy is threefold higher than in patients on conventional insulin therapy and 55% of all episodes occurred in sleep. Prevention of hypoglycemia or the restoring of euglycemia involve the dissipation of metabolic insulin effects and activation of counterregulatory hormone responses (glucagon, catecholamines, growth hormone, cortisol). Among counterregulatory mechanisms there exists hierarchy. The glycemic threshold for release of glucoregulatory hormones in normal people is about 3.8 mmol/l. The glucose counterregulatory system is often impaired in patients with diabetes mellitus with the onset early after diagnosis of diabetes mellitus. Impaired glucagon response is almost universally present after 5 years of diabetes. The defect is selective and the mechanism is not fully explained. Most often it is considered a defect in signal perception of alfa-cells, a rearrangement of islets of Langerhans with predominance of delta-cells or mechanism of central adaptation. After 5-10 years of diabetes glucose counterregulation becomes further impaired with a defect in epinephrine secretion. A possible mechanism is the abnormality at the CNS level. Autonomic neuropathy is a contributory factor. Defective hormonal counterregulation correlates well with duration of diabetes and strict glycemic control. If the glucagon response is intact the hormonal counterregulation is sufficient even in the presence of the impairment of other glucoregulatory factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed2004

Defective acidification of intracellular organelles results in aberrant secretion of cathepsin D in cancer cells.

Aberrant secretion of lysosomal hydrolases such as (pro)cathepsin D (proCD) is a common phenotypic change in many human cancers. Here we explore the underlying molecular defect(s) and find that MCF-7 breast and CaCo-2 colorectal cancer cells that are unable to acidify their endosomal compartments secreted higher amounts of proCD than did acidification-competent cancer cell types. The latter secreted equivalent amounts of proCD only after dissipation of their organellar pH gradients with NH(4)Cl. Assessing the critical steps that resulted in proCD secretion revealed that the Golgi-associated sorting receptor for CD, i.e. the cation-independent mannose-6-phosphate receptor (MPR300), was aberrantly distributed in acidification-defective MCF-7 cells. It accumulated mainly in late endosomes and/or lysosomes as a complex with its ligand (proCD or intermediate CD), as evidenced by its co-localization with both CD and LAMP-2, a late endosome/lysosome marker. Our immunoprecipitation analyses also showed that MCF-7 cells possessed 7-fold higher levels of receptor-enzyme complexes than did acidification-competent cells. NH(4)Cl induced similar receptor redistribution into LAMP-2-positive structures in acidification-competent cells but not in MCF-7 cells. The receptor also recovered its normal Golgi localization upon drug removal. Based on these observations, we conclude that defective acidification results in the aberrant secretion of proCD in certain cancer cells and interferes mainly with the normal disassembly of the receptor-enzyme complexes and efficient receptor reutilization in the Golgi.

Acids↗
PubMed1997

Transcription factor abnormalities as a cause of beta cell dysfunction in diabetes: a hypothesis.

Well-characterized defects in insulin secretion, most notably a loss of glucose-induced insulin secretion, are found in virtually all forms of NIDDM, as well as in early IDDM. Similar abnormalities have been found in all animal models of diabetes in which they have been studied. A novel hypothesis is being proposed to explain the mechanisms responsible for these alterations. Many abnormalities in the various steps of glucose-induced insulin secretion have been identified in rodent models of diabetes, but none by itself seems sufficient to explain the defects. These include a loss of GLUT2, glycogen accumulation, glucose recycling, abnormal glucokinase or hexokinase, altered mitochondrial glycerol phosphate dehydrogenase (mGPDH) activity, abnormal ion channel function and beta cell degranulation. We propose that optimal secretory function is dependent upon the unique differentiation of beta cells that is maintained by a set of transcription factors and that this control is disrupted by the diabetic state. Therefore, we propose that key transcription factors are affected even when beta cells are stressed by insulin resistance in very earliest stages of diabetes and that the abnormality becomes more severe as full-blown diabetes develops, which leads to loss of beta cell differentiation and a resultant derangement of insulin secretion.

Animals↗
PubMed1997

Determinants of abnormal gonadotropin secretion in clinically defined women with polycystic ovary syndrome.

UNLABELLED: Polycystic ovary syndrome (PCOS) is a heterogeneous disorder of reproductive age women characterized in its broadest definition by the presence of oligoamenorrhea and hyperandrogenism and the absence of other disorders. Defects of gonadotropin secretion, including an elevated LH level, elevated LH to FSH ratio, and an increased frequency and amplitude of LH pulsations have been described, but the prevalence of these defects in a large, unbiased population of PCOS patients has not been determined. Sixty-one women with PCOS defined by oligomenorrhea and hyperandrogenism and 24 normal women in the early follicular phase had LH samples obtained every 10 min for 8-12 h. Pool LH levels from the frequent sampling studies were within the normal range in the 9 PCOS patients (14.8%) who were studied within 21 days after a documented spontaneous ovulation. Excluding these post-ovulatory patients, 75.0% of the PCOS patients had an elevated pool LH level (above the 95th percentile of the normal controls), and 94% had an elevated LH to FSH ratio. In the anovulatory PCOS patients, pool LH correlated positively with 17-OH progesterone (R = 0.30, P = 0.03), but not with estradiol, estrone, testosterone, androstenedione, or DHEA-S. Pool LH and LH to FSH ratio correlated positively with LH pulse frequency (R = 0.40, P = 0.004 for pool LH, and R = 0.39; P = 0.005 for LH/FSH). There was also a strong negative correlation between pool LH and body mass index (BMI) (R = -0.59, P < 10(-5)). The relationship between BMI and LH secretion in the PCOS patients appeared to be strongest with body fatness, as pool LH was correlated inversely with percent body fat, whether measured by skinfolds (R = -0.61, P < 10(-5)), bioimpedance (R = -0.55, P < 10(-4)), or dual energy x-ray absorptiometry (DEXA) (R = -0.70, P = 0.001; n = 18 for DEXA only). By DEXA, the only body region that was highly correlated with pool LH was the trunk (R = -0.71, P = 0.001). The relationship between body fatness and LH secretion occurred via a decrease in LH pulse amplitude (R = -0.63, P < 10(-5) for BMI; R = -0.58, P < 10(-4) for bioimpedance; and R = -0.64, P = 0.004 for whole body DEXA), with no significant change in pulse frequency with increasing obesity (R = -0.17, P = 0.23 for BMI). IN CONCLUSION: 1) the prevalence of gonadotropin abnormalities is very high in women with PCOS selected on purely clinical grounds, but is modified by recent spontaneous ovulation; 2) the positive relationship between LH pulse frequency and both pool LH and LH to FSH ratio supports the hypothesis that a rapid frequency of GnRH secretion may play a key etiologic role in the gonadotropin defect in PCOS patients; 3) pool LH and LH pulse amplitude are inversely related to body mass index and percent body fat in a continuous fashion; and 4) the occurrence of a continuous spectrum of gonadotropin abnormalities varying with body fat suggests that nonobese and obese patients with PCOS do not represent distinct pathophysiologic subsets of this disorder.

Adolescent↗
PubMed1987

Normalization of immunoregulatory T-helper T-suppressor sublineages and cell-mediated immunity by isoprinosine in vitro in the early stages of AIDS.

Applying flow cytometric analysis and a panel of monoclonal antibodies that define functional subsets and stages of lymphocyte differentiation, we found both inducer and suppressor regulating subsets of helper T cells to be depressed with concurrent increase in the functionally active effector suppressor T cells in prodromal homosexuals and patients with AIDS. Concomitantly a broad spectrum of aberrations in all stages of B cell developments were observed. Failure of isolated peripheral blood lymphocytes from these subjects to respond to formalin-fixed Staphylococcus aureus cowan 1 (SAC) indicated intrinsic defects in their resting B cells, while impairment in pokeweed mitogen (PWM)-induced blastogenesis coupled with increased levels of Ig secretion signified regulatory defects in their mature B cells, which may be related to helper-suppressor dysfunctions. Based on these findings, a multifactorial immunodysfunction in AIDS was proposed. The antiviral biological modulator drug isoprinosine was shown to enhance PWM-induced, T-cell dependent, B-cell blastogenesis and normalize the spontaneous secretion of Ig while showing no modulative effects on SAC-induced (resting B-cell) transformations. It also modified, in a selective fashion, the phenotypic coexpression of both HLA-DR and Leu8 antigen on helper and suppressor T cells. Among prodromal subjects at risk to develop AIDS, isoprinosine augmented the expression of both helper T-cell subsets while reducing the number of suppressor effector cells and activated suppressor cells. These interferences with the helper-suppressor regulatory loop may explain the therapeutic efficacy of this drug in the early stages of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Relationship of insulin clearance and secretion to insulin sensitivity in non-diabetic Mexican Americans.

The antecedents of type II diabetes, while still controversial, are thought to involve decreased insulin sensitivity and compensatory hypersecretion of insulin. Mexican Americans have a three-fold excess risk of type II diabetes and non-diabetic Mexican Americans are characterized by hyperinsulinaemia and insulin resistance. Few data exist, however, on whether there are defects in insulin secretion and/or clearance in this population. We examined insulin sensitivity, secretion and clearance using combined insulin and C-peptide measurements analysed by the minimal model technique of Bergman and colleagues in 10 non-obese, normoglycaemic Mexican Americans and 11 age, sex and obesity-matched non-Hispanic whites. Mexican Americans had significantly decreased insulin sensitivity (SI 4.06 s. 7.56, P = 0.017), higher first phase insulin secretion (1.03 nM vs. 0.72 nM) and decreased insulin clearance (0.099 vs. 0.161) than non-Hispanic whites. Thus, normal Mexican Americans have higher rather than lower insulin secretion suggesting that lower insulin sensitivity may be an early defect in this ethnic group. In addition, they have reduced insulin clearance. Moreover, insulin sensitivity and insulin clearance were positively correlated. We thus speculate that decreased insulin clearance may represent a further autoregulatory mechanism in addition to increased insulin secretion to compensate for decreased insulin sensitivity.

Adult↗
PubMed1993

Molecular cloning and characterization of 13 out genes from Erwinia carotovora subspecies carotovora: genes encoding members of a general secretion pathway (GSP) widespread in gram-negative bacteria.

The chemical mutagen ethylmethanesulphonate (EMS) has been used to generate mutants of Erwinia carotovora subspecies carotovora which are defective in the secretion of pectinases (Pel) and cellulases (Cel) but unaltered for protease (Prt) secretion. Such mutants, called Out-, still synthesize Pel and Cel but these enzymes accumulate within the periplasm. Cosmid clones carrying wild-type E. carotovora ssp. carotovora DNA, identified by their ability to restore the Out+ phenotype when transferred to some Out- mutants, were classified into six complementation groups using cosmids and cosmid derivatives. Analysis of the nucleotide sequence of a 12.7 kb DNA fragment, encompassing complementing cosmid inserts, revealed a coding capacity for 13 potential open reading frames (ORFs), and these were designated outC-outO. Some of the out gene products were visualized using a T7 gene 10 expression system. The predicted Out proteins are highly similar to components of extracellular enzyme secretion systems from a diverse range of eubacteria including Erwinia chrysanthemi, Klebsiella oxytoca, Aeromonas hydrophila, Pseudomonas aeruginosa and Xanthomonas campestris. Lower levels of similarity exist between Ecc Out proteins and components of macromolecular trafficking systems from Bacillus subtilis, Haemophilus influenzae, Agrobacterium tumefaciens, Yersinia pestis and a protein involved in the morphogenesis of filamentous bacteriophages such as M13.

Amino Acid Sequence↗
PubMed1975

Effects of obesity and caloric intake on biliary lipid metabolism in man.

The effects of obesity and caloric intake on biliary lipid metabolism were investigated in a series of related studies. The degree of saturation of gallbladder bile with cholesterol was found to be significantly higher in a group of 23 obese healthy subjects than in a group of 23 nonobese controls matched for age, sex, and race. Bile was also significantly more saturated in 11 obese subjects before than after weight reduction. To determine whether supersaturated bile in obesity is due to excessive secretion of cholesterol or to deficient secretion of bile acids and phospholipids, the hepatic outputs of these three lipids were measured during constant duodenal infusion of formula in the same 11 subjects before and after weight reduction. Weight reduction resulted in significant reduction of cholesterol output but not of bile acid or phospholipid output. Moreover, very obese subjects were found to have cholesterol secretion rates markedly higher than less obese subjects previously studied by the same method. In obese subjects, bile was supersaturated with cholesterol despite increased bile acid pool sizes and increased secretion rates of bile acids and phospholipids. Supersaturated bile in the obese could therefore be attributed to a single defect in lipid secretion, namely, an excessive output of cholesterol. To determine whether the rate of caloric intake can account for the effects of obesity on biliary lipid composition and secretion, nine obese white men were studied on a weight maintenance diet and then during weight reduction on a 1,000 cal diet. As compared to weight maintenance, chronic caloric restriction resulted in reduced outputs of cholesterol, bile acids, and phospholipids, reduced bile acid pool size, and reduced synthesis and fecal excretion of cholesterol. Saturation of bile with cholesterol did not decrease during weight reduction, evidently because of the mobilization of cholesterol from adipose stores and the marked reduction in bile acid and phospholipid output observed during chronic caloric restriction. Acute alterations in caloric infusion rates did not fully reproduce the effects of chronic administration of high and low calorie diets. Likewise, chronic intake of hypercaloric diets by nonobese subjects did not reproduce the cholesterol hypersecretion characteristic of the obese. Thus, increased cholesterol secretion in obese subjects could not be fully explained by the amount of calories they ingested to maintain stable weight. It is concluded that obesity is characterized by excessive hepatic secretion of cholesterol which results in supersaturated bile.

Adipose Tissue↗
PubMed1992

CFTR!

Cystic fibrosis (CF) is a fatal genetic disease primarily affecting Caucasians, although cases have been reported from other ethnic groups. CF has a complex etiology, but it is chiefly a disease of electrolyte transport and is characterized by defects in fluid secretion by several epithelia, including the sweat duct, exocrine pancreas, and the pulmonary airways. The link between CF and a defect in cAMP-mediated Cl- transport in secretory epithelia was established in the early 1980s. Since then, numerous electrophysiological studies have focused on the characterization and regulation of individual Cl- channels underlying the macroscopic Cl- currents of secretory epithelia in the airways, sweat ducts, and gut. In this review the results of these studies in the light of current knowledge of the function of the CF gene product, the CF transmembrane conductance regulator (CFTR) protein, will be analyzed. The CFTR protein is a member of a family of ATP-binding proteins that act as unidirectional solute pumps. These proteins are membrane spanning, are found in both prokaryotic and eukaryotic cells, and have two ATP-binding domains. The family includes the p-glycoproteins that are involved with the expression of multidrug resistance in certain tumor cells. The majority of CF chromosomes (70%) have a single codon deletion that translates to a missing phenylalanine residue at position 508 (delta F508) of the protein. Unique for this family of proteins, the CFTR protein possesses an additional highly charged domain (the R domain) containing several consensus polypeptide sequences for kinase phosphorylation. Although CFTR bears structural resemblance to this family of ATP-dependent pumps, overexpression of the protein in a variety of different cell types is associated with the appearence of a cAMP-sensitive Cl- channel. We critically examine current information concerning the structure-function relationships of the CFTR protein obtained from both electrophysiological and biochemical approaches. We also summarize recent evidence suggesting that the CFTR protein may act as a pump and a channel, a hypothesis in keeping with the multifaceted nature of the disease.

Adenosine Triphosphate↗
PubMed2000

Overnight inhibition of insulin secretion restores pulsatility and proinsulin/insulin ratio in type 2 diabetes.

Impaired insulin secretion in type 2 diabetes is characterized by decreased first-phase insulin secretion, an increased proinsulin-to-insulin molar ratio in plasma, abnormal pulsatile insulin release, and heightened disorderliness of insulin concentration profiles. In the present study, we tested the hypothesis that these abnormalities are at least partly reversed by a period of overnight suspension of beta-cell secretory activity achieved by somatostatin infusion. Eleven patients with type 2 diabetes were studied twice after a randomly ordered overnight infusion of either somatostatin or saline with the plasma glucose concentration clamped at approximately 8 mmol/l. Controls were studied twice after overnight saline infusions and then at a plasma glucose concentration of either 4 or 8 mmol/l. We report that in patients with type 2 diabetes, 1) as in nondiabetic humans, insulin is secreted in discrete insulin secretory bursts; 2) the frequency of pulsatile insulin secretion is normal; 3) the insulin pulse mass is diminished, leading to decreased insulin secretion, but this defect can be overcome acutely by beta-cell rest with somatostatin; 4) the reported loss of orderliness of insulin secretion, attenuated first-phase insulin secretion, and elevated proinsulin-to-insulin molar ratio also respond favorably to overnight inhibition by somatostatin. The results of these clinical experiments suggest the conclusion that multiple parameters of abnormal insulin secretion in patients with type 2 diabetes mechanistically reflect cellular depletion of immediately secretable insulin that can be overcome by beta-cell rest.

Blood Glucose↗
PubMed1992

cAMP stimulates bicarbonate secretion across normal, but not cystic fibrosis airway epithelia.

Adenosine 3',5'-cyclic monophosphate stimulates chloride (Cl-) secretion across airway epithelia. To determine whether cAMP also stimulates HCO3- secretion, we studied cultured canine and human airway epithelial cells bathed in a HCO3-/CO2-buffered, Cl(-)-free solution. Addition of forskolin stimulated an increase in short-circuit current that was likely a result of bicarbonate secretion because it was inhibited by a HCO3(-)-free solution, by addition of the carbonic anhydrase inhibitor, acetazolamide, or by mucosal addition of the anion channel blocker, diphenylamine 2-carboxylate. The current was dependent on Na+ because it was inhibited by removal of Na+ from the submucosal bathing solution, by addition of the Na+ pump inhibitor, ouabain, or by addition of amiloride (1 mM) to the submucosal solution. An increase in cytosolic Ca2+ produced by addition of a Ca2+ ionophore also stimulated short-circuit current. These data suggest that cAMP and Ca2+ stimulate HCO3- secretion across airway epithelium, and suggest that HCO3- leaves the cell across the apical membrane via conductive pathways. These results may explain previous observations that the short-circuit current across airway epithelia was not entirely accounted for by the sum of Na+ absorption and Cl- secretion. The cAMP-induced secretory response was absent in cystic fibrosis (CF) airway epithelial cells, although Ca(2+)-stimulated secretion was intact. This result suggests that HCO3- exist at the apical membrane is through the Cl- channel that is defectively regulated in CF epithelia. These results suggest the possibility that a defect in HCO3- secretion may contribute to the pathophysiology of CF pulmonary disease.

Animals↗
PubMed1995

Isolation of a cDNA clone encoding a KATP channel-like protein expressed in insulin-secreting cells, localization of the human gene to chromosome band 21q22.1, and linkage studies with NIDDM.

The metabolism of glucose in insulin-secreting cells leads to closure of ATP-sensitive K+ channels (KATP), an event that initiates the insulin secretory process. Defects in insulin secretion are a common feature of non-insulin-dependent diabetes mellitus (NIDDM), and the beta-cell KATP that couples metabolism and membrane potential is a candidate for contributing to the development of this clinically and genetically heterogeneous disorder. We screened a hamster insulinoma cDNA library by low-stringency hybridization with a probe coding for the G-protein-coupled inwardly rectifying K+ channel GIRK1/KGA and isolated clones encoding a protein, KATP-2, whose sequence is 90% similar to that of the recently described KATP-1, an ATP-sensitive K+ channel expressed in heart and other tissues. RNA blotting showed that KATP mRNA was present in insulin-secreting cells and brain but not in heart. To assess the contribution of KATP-2 to the development of NIDDM, the human KATP-2 gene (symbol KCNJ7) was isolated and mapped to chromosome band 21q22.1 by fluorescence in situ hybridization. A simple tandem repeat DNA polymorphism, D21S1255, was identified in the region of the KATP-2 gene, and linkage studies between this marker and NIDDM were carried out in a group of Mexican-American sib pairs with NIDDM. There was no evidence for linkage between D21S1255 and NIDDM, indicating that KATP-2 is not a major susceptibility gene in this population.

Adenosine Triphosphate↗
PubMed1989

Idiopathic isolated ACTH deficiency and the response to CRF.

A 26-year-old woman, intermittently symptomatic over 8 yr, was evaluated for weakness, lightheadedness, and gastrointestinal complaints. She was found to have negligible plasma cortisol and low to low-normal plasma ACTH levels. Although serum cortisol was responsive to ACTH stimulation, metyrapone and insulin-induced hypoglycemia were unable to stimulate pituitary driven adrenal activity. Hypothalamic and pituitary functions were otherwise intact. CRF administration failed to stimulate any increase in plasma ACTH or cortisol levels and CT scanning failed to reveal any anatomic abnormality of the sella or suprasellar areas consistent with an acquired isolated defect in pituitary ACTH secretion. These studies support the impression that the primary defect in isolated idiopathic ACTH deficiency is failure of pituitary ACTH-secreting cells.

Adrenocorticotropic Hormone↗
PubMed1989

Glucose metabolism and insulin secretion in infants with symptomatic ventricular septal defect.

Nineteen infants with symptomatic ventricular septal defect (VSD) were examined on, altogether, 26 occasions, when each was given an intravenous glucose tolerance test (IVGTT); concentrations of insulin- and C-peptide in plasma were determined. Comparisons were made with 14 healthy infants of the same age. The VSD infants were growth retarded with lower weight/age and length/age ratios. Glucose tolerance as indicated by glucose fasting levels and response to intravenous glucose tolerance test, including glucose disappearance rate, did not differ between the two groups. In response to the glucose load, insulin in plasma was significantly less in VSD infants. In response to the IVGTT, insulin secretion rate calculated from C-peptide levels in plasma was significantly elevated in the VSD group. We conclude that compared to healthy infants, those with symptomatic VSD have normal glucose tolerance, increased secretion rate of insulin, but decreased levels of circulating insulin in response to an intravenous glucose load. We suggest this is so because binding of insulin to peripheral receptors and/or insulin extraction in the liver somehow increases.

Blood Glucose↗
PubMed1999

Ecs, an ABC transporter of Bacillus subtilis: dual signal transduction functions affecting expression of secreted proteins as well as their secretion.

ecs is a three-cistron operon of Bacillus subtilis, encoding proteins with similarity to the ATPase (EcsA) and hydrophobic components (EcsB) of ABC transporters. The ecsA26 point mutation was shown to cause a strong processing defect of a secreted alpha-amylase precursor (preAmyQ) and of three other exoproteins. Northern analysis of the level of amyQ mRNA showed that ecsA26 also decreases amyQ transcription. This effect too was pleiotropic, as judged by a drastic decrease in the expression from an exoprotease promoter of a reporter protein. A knockout mutation of the ecsB cistron caused a processing defect similar to ecsA26 but, unlike ecsA26, did not affect amyQ transcription. These was also no defect in transcription in the ecsA ecsB double mutant. Thus, an intact ecsB product was required for the downregulation of amyQ by the mutant ecsA. These results suggest a dual regulatory function for Ecs, in which Ecs, possibly as part of a signal transduction mechanism, regulates some component(s) of the protein secretion apparatus as well as secretory protein transcription in a co-ordinated fashion.

ATP-Binding Cassette Transporters↗
PubMed1985

Vasopressin secretion in progressive autonomic failure: evidence for defective afferent cardiovascular pathways.

Patients with progressive autonomic failure with multiple system atrophy show a severely blunted response of plasma arginine vasopressin to the stimulus of head-up tilt. Whether this could be due to lesions either at one or more sites within ascending neural pathways from cardiovascular stretch receptors in the thorax or, alternatively, to lesions affecting vasopressin secreting cells within the hypothalamus was investigated. The arginine vasopressin response to an intravenous infusion of hypertonic saline was determined in six patients with progressive autonomic failure. The mean plasma concentration of arginine vasopressin rose from 1.0 to 3.7 pmol/l, a change comparable to that observed in normal controls. This demonstrates normal functioning of the efferent connections from the osmoreceptors within the hypothalamus and suggests that the loss of vasopressin response to head-up tilt is due to lesions in ascending pathways from cardiovascular receptors. There was a significant rise in mean blood pressure during the infusions on patients with progressive autonomic failure, a change which was not observed with the controls. This may have been at least partly caused by the rise in circulating arginine vasopressin concentrations, since these patients have been reported to be extremely sensitive to the pressor effects of arginine vasopressin.

Afferent Pathways↗
PubMed1993

Mechanism of bile acid-induced biliary lipid secretion in the rat: effect of conjugated bilirubin.

We have compared the effects of bilirubin and bilirubin ditaurate (BDT) on biliary phospholipid and cholesterol secretion in unanesthetized normal Wistar (NW) and Groningen Yellow (GY) Wistar rats under various experimental conditions. GY rats express a genetic defect in biliary secretion, but not in hepatic uptake, of various organic anions. Under physiological conditions, NW and GY rats showed similar biliary secretion rates of bile acids and of bilirubin, despite the fact that bilirubin concentrations in GY plasma were 25 times as high and in GY livers three times as high as in NW plasma and livers, respectively. Secretion of cholesterol and phospholipids was not impaired in GY rats under these conditions. Biliary secretion of intravenously injected BDT (3 mumol/100 g body wt) was delayed in eight-day bile-diverted GY rats and showed lower peak values when compared with NW rats. The inhibitory effects of BDT on phospholipid and cholesterol secretion paralleled these differences, being delayed and much less pronounced in GY rats. No overshoot in phospholipid or cholesterol secretion was observed when bilirubin output returned to preinjection values. Stimulation of [14C]choline-labeled phospholipid secretion after a bolus injection of taurochenodeoxycholic acid (1 mumol/100 g body wt) closely followed biliary bile acid concentration. Similarly, inhibition of labeled phospholipid secretion by BDT closely paralleled the biliary bilirubin concentration. Gel filtration studies (Sepharose 4B-CL) under micelle-preserving conditions demonstrated a specific interaction of BDT with biliary bile acids. The presented data indicate that conjugated bilirubin does not inhibit biliary lipid secretion via interaction with bile acids inside the hepatocyte.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗