The Role of the Colon in the Pathogenesis of Hyperchloraemic Acidosis in Ureterosigmoid Anastomosis

1979 ◽  
Vol 57 (4) ◽  
pp. 305-312 ◽  
Author(s):  
J. B. McConnell ◽  
J. Murison ◽  
W. K. Stewart
Keyword(s):  
Colonic Mucosa ◽  
Chloride Concentration ◽  
Direct Consequence ◽  
Normal Subjects ◽  
Ionic Diffusion ◽  
Chloride Absorption ◽  
Total Ammonia ◽  
Colonic Secretion

1. The composition of urine-faeces mixture in seven patients with ureterosigmoid anastomosis has been studied by a dialysis in vivo method using cellulose bags. Urine—faeces dialysate obtained from these patients contained much greater amounts of both bicarbonate and total ammonia than has been reported for faecal dialysate in normal subjects. 2. Total ammonia concentrations in urine– faeces specimens obtained by catheter suggest that urine excreted by the kidneys in these patients becomes increasingly acid with increasing systemic acidosis. The highly alkaline nature of urine-faeces mixtures, especially in acidotic patients, indicates rapid alkalinization of the mixture in the colon. It appears that colonic secretion of bicarbonate is a direct consequence of the acidity of urine excreted by the kidney and draining into the colon. 3. The study suggests that the development of hyperchloraemic acidosis in patients with ureterosigmoid anastomosis is due to bicarbonate secretion by the colonic mucosa, with concomitant chloride absorption. With the development of metabolic acidosis, rapid alkalinization of the urine still occurs in the colon, but during further retention of the urine-faeces in the colon some reabsorption of bicarbonate occurs, probably in part by ionic diffusion since chloride concentration in the lumen increases. 4. Evidence suggestive of non-ionic diffusion of ammonia was found in only one patient. It seems probable that higher rates of urea breakdown in other patients mask the expected relationship between total ammonia and bicarbonate.

scholarly journals Functional Characterization of Membrane Sialyltransferase Activity of Human Platelets

1977 ◽  
Author(s):  
K. K. Wu ◽  
C. Ku ◽  
C. Smith
Keyword(s):  
Enzyme Activity ◽  
Functional Characterization ◽  
Adenosine Diphosphate ◽  
Normal Subjects ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Transferase Activity ◽  
Platelet Surface

To evaluate the role of membrane sialyltransferase in the initiation of platelet aggregation, we studied the stimulatory effect of epinephrine and adenosine diphosphate and the inhibitory effect of aspirin on the platelet surface sialyl transferase activity. The enzyme activity was assayed under optimal conditions as determined previously. The assay mixture consisted of intact washed human platelets, CMP-14C-sialic acid, desialated fetuin, Mn2+ and buffer to a final volume of 1 ml. The enzyme activity was enhanced to 172% of control by 1μH, 152% by 5μM and 146% by 10μM epinephrine. Adenosine diphosphate enhanced the enzyme activity to a lesser extent:103% at 1μM and 113% at 5μM. In contrast, aspirin inhibited the enzyme activity to 46% of control when 10μg/ml of aspirin was used. Higher concentrations of aspirin failed to cause further inhibition. In the in-vivo experiment, 600 mg aspirin was given to normal subjects and the surface enzyme activity was determined 12 hours later. The enzyme activity reduced to 43% following aspirin administration. Furthermore, we studied the enzyme activity in a patient with “aspirin-like” release disorder. While the mean surface enzyme activity of 10 normal subjects was 1.56 + 0.21 (S. D.) pmole-hr-1 per 108 platelets, the enzyme activity of the patient was only 0.91 pmole.hr-l. The results strongly suggest that the membrane sialyltransferase plays an important part in the initiation of platelet release reaction.

scholarly journals Hyperglycemia Acutely Increases Monocyte Extracellular Signal-Regulated Kinase Activity in Vivo in Humans

2001 ◽  
Vol 86 (3) ◽  
pp. 1301-1305 ◽  
Author(s):  
Giulio Ceolotto ◽  
Alessandra Gallo ◽  
Michelangelo Sartori ◽  
Roberto Valente ◽  
Elisabetta Baritono ◽  
...  
Keyword(s):  
Normal Subjects ◽  
Mitogen Activated Protein Kinase ◽  
Glucose Levels ◽  
Extracellular Signal ◽  
Patients With Diabetes ◽  
Mitogen Activated Protein ◽  
Negative Role ◽  
Long Term Prognosis

Glycemic spikes may negatively affect the long-term prognosis of patients with diabetes. Extracellular signal-regulated kinases (ERKs) are intracellular mediators of cell proliferation, and they can be activated in response to high glucose levels. However, the modifications of their activity in response to hyperglycemia have been poorly investigated, in vivo, in humans. Thus, we sought to determine in circulating monocytes: 1) the role of hyperglycemia in ERKs activity and phosphorylation, and 2) whether hyperglycemia affects mitogen-activated protein kinase kinase (MEK) activity and mitogen-activated protein phosphatase-1 (MKP-1) expression. These goals were performed in five normal subjects. Baseline monocyte ERKs activity was 60 ± 5 pmol/min·mg protein; when exogenous hyperglycemia was induced, both monocyte ERKs activity (81 ± 11 pmol/min·mg protein; P < 0.05) and phosphorylation significantly increased (P < 0.01). MEK activity was significantly increased by hyperglycemia (1251 ± 136 vs. 2000 ± 42 cpm; P = 0.0017), whereas no changes were observed in MKP-1 expression. We conclude that hyperglycemia acutely stimulates ERKs activity and phosphorylation in human monocytes by the MEK pathway in vivo. These findings may be relevant in understanding the negative role of acute hyperglycemia on monocyte pathophysiology.

Evidence for the Expression of Urokinase-type Plasminogen Activator by Human Venous Endothelial Cells In Vivo

1998 ◽  
Vol 80 (12) ◽  
pp. 961-967 ◽  
Author(s):  
L. Camoin ◽  
R. Pannell ◽  
F. Anfosso ◽  
J. P. Lefevre ◽  
J. Sampol ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Plasminogen Activator ◽  
Animal Studies ◽  
Normal Subjects ◽  
Immunomagnetic Beads ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Tissue Plasminogen

SummaryEndothelial cells (ECs) in culture synthesize and secrete urokinase-type plasminogen activator (u-PA), but the normal vascular endothelium is believed to synthesize only tissue plasminogen activator (t-PA), which is thought to be responsible for intravascular fibrinolysis. More recently, animal studies have shown that the biological role of u-PA in fibrinolysis has been underestimated, prompting a re-examination of its synthesis by the endothelium. In this study, we investigated whether u-PA was synthesized by non-atherosclerotic endothelial cells in vivo by testing ECs dislodged by venipuncture from 12 normal volunteers and 17 patients admitted for plasmapheresis. The ECs were isolated with an anti-endothelial monoclonal antibody coupled to immunomagnetic beads and characterized by morphology and by labelling for vWF, CD31, and UEA-1 binding. U-PA antigen was found in 50% of the ECs from the normal subjects and in 60% of those from patients. U-PA enzymatic activity on zymograms was detected in 50% of the normal samples and 60% of the patient samples, with the latter being more frequently and more strongly positive. U-PA mRNA was found in all the normal and patient samples tested. The results indicate that u-PA is synthesized by the venous endothelium in vivo but that its expression is highly variable.

A novel colon-specific steroid prodrug enhances sodium chloride absorption in rat colitis

1995 ◽  
Vol 269 (2) ◽  
pp. G210-G218
Author(s):  
R. N. Fedorak ◽  
N. Cui ◽  
D. R. Friend ◽  
K. L. Madsen ◽  
L. R. Empey
Keyword(s):  
Sodium Chloride ◽  
Colonic Mucosa ◽  
Epithelial Transport ◽  
Free Drug ◽  
Fluid Absorption ◽  
Ussing Chambers ◽  
Mucosal Integrity ◽  
Chloride Absorption

A recently synthesized novel colon-specific dexamethasone prodrug, dexamethasone-beta-D-glucuronide, delivers efficacious amounts of dexamethasone to the colon with limited adrenal suppressive effects. During experimentally induced colitis in rats, the dexamethasone prodrug is significantly more potent than free dexamethasone in improving colonic fluid and electrolyte absorptive injury. The present studies examined whether the improvement in colonic absorption seen with the prodrug occurred as a consequence of alterations in sodium and chloride epithelial transport. The efficacy of the dexamethasone prodrug and free dexamethasone were tested in an acetic acid-induced rat model of colitis. Healing of the induced colitis was assessed by measuring net colonic fluid absorption and surface area ulceration. Transmural unidirectional fluxes of 22Na and 36Cl across sheets of colonic mucosa were measured in Ussing chambers. Treatment of colitis with the prodrug delivered a sixfold higher concentration of dexamethasone to the colon than did treatment with the free drug. The prodrug accelerated healing of colitis by returning in vivo colonic fluid absorption to normal and virtually eliminated colonic macroscopic ulceration, whereas the free drug did not. In vitro transmural fluxes demonstrated that, in addition to repair of mucosal integrity, the prodrug enhanced electroneutral sodium chloride absorption over and above that seen in control animals or after treatment with the free drug. Both the prodrug and the free drug limited theophylline-mediated net chloride and sodium secretion, an effect that would be consistent with the antidiarrheal effect induced by these drugs in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

The Role of the Colon in Urea Metabolism in Man

1976 ◽  
Vol 50 (1) ◽  
pp. 51-59 ◽  
Author(s):  
J. A. Gibson ◽  
N. J. Park ◽  
G. E. Sladen ◽  
A. M. Dawson
Keyword(s):  
Dietary Protein ◽  
Colonic Mucosa ◽  
Normal Subjects ◽  
Urea Concentration ◽  
Low Protein ◽  
Urea Content ◽  
Colonic Lumen ◽  
Urea Metabolism ◽  
Protein Diets

1. The urea content of ileostomy effluent has been measured by the urease method as an indirect estimate of the urea concentration in the lumen of the normal ileum. 2. The plasma disappearance of intravenously administered [14C]urea was used to study intestinal urea breakdown. Normal subjects on high and low protein diets and patients with either excised (i.e. with ileostomies) or excluded colons were studied. 3. The 24 h intestinal urea breakdown was considerably greater than the quantity of urea estimated to be entering the colon from the ileum and across the colonic mucosa. 4. Intestinal urea breakdown increased with increase in dietary protein and decreased with, but was not abolished by, exclusion or excision of the colon. 5. Our results suggest that the colonic lumen is not the only site of intestinal ureolysis and that significant quantities of urea must be broken down either at a juxtamucosal site or in the ileum.

The Interrelations of Faecal Ammonia, pH and Bicarbonate: Evidence of Colonic Absorption of Ammonia by Non-Ionic Diffusion

1972 ◽  
Vol 43 (1) ◽  
pp. 101-114 ◽  
Author(s):  
P. F. Down ◽  
L. Agostini ◽  
J. Murison ◽  
O. M. Wrong
Keyword(s):  
Significant Negative Correlation ◽  
Ammonia Concentration ◽  
Ionic Diffusion ◽  
Urine Ph ◽  
Unionized Ammonia ◽  
Total Ammonia ◽  
Colonic Secretion ◽  
Ammonia Bicarbonate ◽  
A Minor ◽  
Faecal Ph

1. Ammonia, bicarbonate and pH were measured in samples of faecal dialysate from thirteen healthy subjects taking free diets. To observe the effect of marked changes in faecal pH, three subjects were also studied while taking 25 mmol/day of MgCO3 or Na2SO4 by mouth. Both salts increased stool weight without causing diarrhoea, but stool pH was significantly increased by MgCO3 and decreased by Na2SO4. 2. The total ammonia concentration and pH of faecal dialysate were very variable, but showed a highly significant negative correlation similar to that already established in man between urinary excretion of ammonia and urine pH. This relationship was more marked when individual subjects were studied while faecal pH was deliberately varied by administration of MgCO3 and Na2SO4. 3. Faecal bicarbonate concentrations were positively correlated with pH. Faecal Pco2 was usually in the range 40–120 mmHg, the higher Pco2 values being found in the more acid samples. Faecal total ammonia concentrations were negatively correlated with faecal bicarbonate. 4. These findings suggest that passive non-ionic diffusion is the main mechanism by which ammonia is absorbed by the colon, but do not exclude a minor contribution from diffusion of ionized ammonium. Colonic secretion of bicarbonate facilitates non-ionic diffusion of ammonia by providing an anion which is also absorbed by non-ionic diffusion, so maintaining an alkaline intraluminal reaction that continues to generate unionized ammonia.

scholarly journals JAM-A regulates permeability and inflammation in the intestine in vivo

2007 ◽  
Vol 204 (13) ◽  
pp. 3067-3076 ◽  
Author(s):  
Mike G. Laukoetter ◽  
Porfirio Nava ◽  
Winston Y. Lee ◽  
Eric A. Severson ◽  
Christopher T. Capaldo ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Barrier Function ◽  
Colonic Mucosa ◽  
Mucosal Inflammation ◽  
Wild Type ◽  
Mucosal Permeability ◽  
Interfering Rna ◽  
Lymphoid Aggregates

Recent evidence has linked intestinal permeability to mucosal inflammation, but molecular studies are lacking. Candidate regulatory molecules localized within the tight junction (TJ) include Junctional Adhesion Molecule (JAM-A), which has been implicated in the regulation of barrier function and leukocyte migration. Thus, we analyzed the intestinal mucosa of JAM-A–deficient (JAM-A−/−) mice for evidence of enhanced permeability and inflammation. Colonic mucosa from JAM-A−/− mice had normal epithelial architecture but increased polymorphonuclear leukocyte infiltration and large lymphoid aggregates not seen in wild-type controls. Barrier function experiments revealed increased mucosal permeability, as indicated by enhanced dextran flux, and decreased transepithelial electrical resistance in JAM-A−/− mice. The in vivo observations were epithelial specific, because monolayers of JAM-A−/− epithelial cells also demonstrated increased permeability. Analyses of other TJ components revealed increased expression of claudin-10 and -15 in the colonic mucosa of JAM-A−/− mice and in JAM-A small interfering RNA–treated epithelial cells. Given the observed increase in colonic inflammation and permeability, we assessed the susceptibility of JAM-A−/− mice to the induction of colitis with dextran sulfate sodium (DSS). Although DSS-treated JAM-A−/− animals had increased clinical disease compared with controls, colonic mucosa showed less injury and increased epithelial proliferation. These findings demonstrate a complex role of JAM-A in intestinal homeostasis by regulating epithelial permeability, inflammation, and proliferation.

Mutual dependence of sodium and chloride absorption by renal distal tubule

1984 ◽  
Vol 247 (6) ◽  
pp. F904-F911 ◽  
Author(s):  
H. Velazquez ◽  
D. W. Good ◽  
F. S. Wright
Keyword(s):  
Chloride Transport ◽  
Chloride Concentration ◽  
Distal Tubule ◽  
Sodium Concentration ◽  
Sodium Absorption ◽  
Similar Extent ◽  
Luminal Membrane ◽  
Chloride Absorption ◽  
Transepithelial Voltage

Sodium transport and chloride transport by the renal distal tubule of rats were studied by in vivo continuous microperfusion to determine the effects of separately altering luminal sodium and chloride concentrations. Results showed that sodium absorption depends on luminal sodium concentration and chloride absorption depends on luminal chloride concentration; both relations are linear between approximately 10 and 100 mM and have slopes of approximately 2.5 pmol X min-1 X mM-1. Sodium absorption is also a saturable function of luminal chloride concentration, and chloride absorption is a saturable function of luminal sodium concentration; the half-maximal chloride and sodium concentrations are approximately 10 mM. Furosemide, 10(-4) M, when added to the fluid used to perfuse this segment inhibited sodium absorption and chloride absorption to a similar extent. Removal of chloride from luminal fluid (replaced with sulfate) and addition of furosemide to the perfusion fluid had little or no effect on the measured transepithelial voltage. The results are consistent with the presence of a mechanism in the luminal membrane of distal tubule cells that couples the absorptive transport of sodium and chloride.

Effect of volume expansion and plasma chloride on function of the loop segment

1983 ◽  
Vol 245 (1) ◽  
pp. F41-F47 ◽  
Author(s):  
B. B. Booker ◽  
R. H. Williams ◽  
R. G. Luke
Keyword(s):  
Volume Expansion ◽  
Chloride Concentration ◽  
Ringer Solution ◽  
Thick Ascending Limb ◽  
Chloride Uptake ◽  
Gradient Effect ◽  
Time Control ◽  
Chloride Absorption ◽  
Plasma Chloride

To determine the effect of acute volume expansion and changes in plasma chloride on fluid and chloride uptake in superficial loop segments of rats, this segment was microperfused in vivo at 22 nl/min with a fluid containing Na 145, Cl and 36Cl 130, and HCO3 15 meq/liter during hydropenia and after acute volume expansion with 0.15 M NaCl, 0.15 M NaHCO3, or an isotonic bicarbonate Ringer (Cl 106 meq/liter) solution. Fractional fluid, chloride, and 36Cl reabsorption and early distal chloride concentration did not change during maintained hydropenia (time control) or during volume expansion with NaCl (plasma chloride 120 meq/liter) or bicarbonate Ringer solution (plasma chloride 104 meq/liter). Absolute and fractional reabsorption of chloride and 36Cl increased, without change in fluid reabsorption, and early distal chloride diminished after infusion of NaHCO3 (plasma chloride 90 meq/liter). It is concluded that acute volume expansion, per se, has no effect on either net fluid or net chloride absorption in the superficial loop segment at the load studied. Hypochloremia is associated with increased net reabsorption of chloride and an increased unidirectional efflux of chloride from the loop segment during acute volume expansion, most likely due to a gradient effect on the thick ascending limb of the loop of Henle.

Abstract 211: The Role of Vascular Amyloid β in the Formation of Microhemorrhages in Cerebral Amyloid Angiopathy

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Susanne J van Veluw ◽  
Andreas Charidimou ◽  
Anand Viswanathan ◽  
Matthew Frosch ◽  
Brian Bacskai ◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Amyloid Β ◽  
Direct Consequence ◽  
Transgenic Animals ◽  
Diagnostic Feature ◽  
Amyloid Angiopathy ◽  
Wild Type ◽  
Cerebral Amyloid

Introduction: Cerebral microhemorrhages are a key diagnostic feature of advanced cerebral amyloid angiopathy (CAA), but the underlying mechanisms remain poorly understood. We investigate the role of vascular Amyloid β (Aβ) in the formation of microhemorrhages in CAA, examining both human tissue and mouse models. Methods: First, we examined the histopathology of microhemorrhages, targeted with post-mortem MRI in humans. Brain slabs from nine cases with moderate/severe CAA were subjected to 7 T MRI. Samples were taken from representative MRI-observed microhemorrhages. On the corresponding histopathological sections we assessed the presence of Aβ in the walls of involved vessels, as well as number of Aβ-positive cortical vessels in areas (<2 mm) surrounding the rupture site. Second, to evaluate microhemorrhage formation in real-time in 3D, we performed in vivo two-photon microscopy in aged APP/PS1 mice with advanced CAA. Mice with previously installed cranial windows were injected with fluorescently labeled anti-fibrin, dextran, and methoxy-XO4 to study clot formation (i.e. microhemorrhages) and their spatial localization in relation to Aβ-positive vessels. Results: Human data: in 7/19 microhemorrhages the involved vessels were preserved. Only one of these vessels was positive for Aβ. Moreover, the density of Aβ-positive cortical vessels was lower close to the site of microhemorrhage (~1 positive vessel/mm 2 ), compared to control areas (~2 positive vessels/mm 2 ). Mouse data: we studied six transgenic ~21 month old APP/PS1 mice and two age-matched wild-type littermates. Mean number of in vivo observed microhemorrhages did not differ between groups (Tg: 1.3 / WT: 1), but the transgenic mice tended to have bigger microhemorrhages (mean size 4706 μm 3 ) than their wild-type controls (2505 μm 3 ). Interestingly, in the transgenic animals only one microhemorrhage was found in close proximity to vascular Aβ deposits. Conclusions: These findings question the widely held assumption that microhemorrhages in CAA are a direct consequence of Aβ deposition in the walls of responsible vessels. Our observations suggest that microhemorrhage formation may not be a direct consequence of more severe CAA locally, but may occur preferentially in areas of relatively low CAA.

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