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Biomedical subjects

R Bataller

Publications and source records attributed to R Bataller.

At least 37 records · Page 2Linked to original sources

Contraction of human hepatic stellate cells activated in culture: a role for voltage-operated calcium channels.

BACKGROUND/AIMS: Voltage-operated calcium channels are essential for the regulation of vascular tone and are potential targets for vasodilating agents. They regulate calcium entry and thereby cell contraction in vascular cell types. Hepatic stellate cells in the activated phenotype have contractile properties and could participate in the regulation of sinusoidal blood flow. Thus, this study was aimed at investigating the presence of voltage-operated calcium channels in human hepatic stellate cells activated in culture and the effects of their stimulation on intracellular calcium concentration ([Ca2+]i) and cell contractility. METHODS: Binding studies using [3H]-nitrendipine were performed to demonstrate the presence of voltage-operated calcium channels. Voltage-operated calcium channels were stimulated by causing cell membrane depolarization either by electrical field stimulation or extracellular high potassium. [Ca2+]i and cell contraction were measured in individual cells loaded with fura-2 using a morphometric method with an epifluorescence microscope coupled to a charge-coupled device-imaging system. RESULTS: Binding studies demonstrated the existence of voltage-operated calcium channels in human activated hepatic stellate cells (7.1+/-1.4x10(4) sites/cell with a Kd of 2.1+/-0.1 nM). Both electrical field stimulation and potassium chloride-induced cell depolarization resulted in a marked and prolonged increase in [Ca2+]i followed by intense cell contraction. The degree of cell contraction correlated with the intensity of calcium peaks. Removal of extracellular calcium or preincubation of cells with nitrendipine, a specific antagonist of voltage-operated calcium channels, completely blocked the effects on [Ca2+]i and cell contraction, whereas preincubation of cells with BayK-8644, a specific agonist of voltage-operated calcium channels, increased calcium peaks and contraction. CONCLUSION: Activated human hepatic stellate cells have a large number of voltage-operated calcium channels, the activation of which is associated with an increase in [Ca2+]i followed by marked cell contraction. Voltage-operated calcium channels probably play an important role in the regulation of activated hepatic stellate cells contractility.

Calcium Channel Blockers↗

Impairment of renal function during moderate physical exercise in cirrhotic patients with ascites: relationship with the activity of neurohormonal systems.

Moderate physical exercise does not affect glomerular filtration rate (GFR) and renal excretory function in normal subjects. This study is aimed at assessing the effects of moderate physical exercise on renal function in 21 nonazotemic cirrhotic patients with ascites. Arterial pressure, heart rate, and renal function were assessed in the patients after 2 hours in the supine position and during 30 minutes of moderate cycloergometric exercise in the sitting position. The activity of the renin-aldosterone and sympathetic nervous systems and the plasma levels of antidiuretic hormone (ADH) and atrial natriuretic peptide (ANP) were determined at the end of each period. Physical exercise induced a marked reduction in GFR (75 +/- 10 to 49 +/- 6 mL/min), free-water clearance (6.1 +/- 1 to 3.4 +/- 1 mL/min), and sodium excretion (7.8 +/- 2 to 4.3 +/- 1 microEq/min) in 10 patients (Group I). In the remaining 11 cases (Group II) there were no changes in these parameters. Renal perfusion significantly decreased in both groups although the reduction was greater in Group I (-34.7% +/- 4.6% vs. -7.5% +/- 3.1%, P < .001). Physical exercise was associated with a significant and comparable increase in arterial pressure, heart rate, and plasma levels of renin, aldosterone, and norepinephrine (NE) in the two groups of patients. The ANP concentration did not change. Patients from Groups I and II differed significantly (P < .05) only in plasma renin activity (PRA) and NE concentration, which were higher in Group I patients both in the supine rest (renin: 4.7 +/- 1.6 vs. 1.4 +/- 0.5 ng/mL x h; NE: 576 +/- 115 vs. 288 +/- 42 pg/ mL) and during exercise (renin: 7.1 +/- 1.8 vs. 2.6 +/- 1 ng/ mL x h; NE: 925 +/- 135 vs. 630 +/- 90 pg/mL). In conclusion, moderate physical exercise has no detrimental effects on renal function in cirrhotic patients with ascites with no or mild activation of the renin-aldosterone and sympathetic nervous systems. However, moderate physical exercise causes a marked impairment in the renal function of patients with ascites with marked stimulation of these vasoconstrictor systems.

Ascites↗

Spontaneous bacterial peritonitis in patients with cirrhosis undergoing selective intestinal decontamination. A retrospective study of 229 spontaneous bacterial peritonitis episodes.

BACKGROUND/AIMS: Selective intestinal decontamination with norfloxacin is widely used to prevent spontaneous bacterial infections in cirrhosis. The study was performed to compare the spontaneous bacterial peritonitis occurring in patients with and without prophylactic norfloxacin. METHODS: Two hundred and twenty-nine consecutive episodes of spontaneous bacterial peritonitis, (193 in patients without (Group A) and 36 in patients with norfloxacin prophylaxis (Group B)), were retrospectively analyzed. In 100 episodes (86 and 14, respectively), the responsible organism was isolated in ascitic fluid. RESULTS: Clinical and laboratory data at diagnosis were comparable in both groups. There were marked differences (p < 0.001) between group A and B in the frequency of peritonitis caused by gram-negative (67.4% vs. 14.3%) and gram-positive (30.2% vs. 78.6%) bacteria. There were three polymicrobial episodes. Bacteria resistant to cefotaxime and gram-negative bacilli resistant to quinolones were isolated in ascitic fluid in nine (seven in Group A and two in Group B) and three episodes (all in Group A), respectively. No differences in the course of infection and patient survival were observed between groups. CONCLUSIONS: Spontaneous bacterial peritonitis in patients with and without prophylaxis with norfloxacin are not different in clinical features, response to treatment and prognosis. Spontaneous bacterial peritonitis caused by gram-negative organisms resistant to quinolones is extremely uncommon in patients with cirrhosis receiving prophylactic norfloxacin.

Adult↗

Effect of therapeutic paracentesis on plasma volume and transvascular escape rate of albumin in patients with cirrhosis.

BACKGROUND/AIMS: Circulatory abnormalities with activation of vasoconstrictor systems after large-volume paracentesis are generally considered secondary to an increased extravasation of fluid from the intravascular compartment to the extravascular space with subsequent reduction in plasma volume. To test this hypothesis, plasma volume, the transvascular escape rate of albumin, the absolute escape rate of albumin and the activity of vasoconstrictor systems were measured in 25 cirrhotic patients with ascites in baseline conditions and 2 days after total paracentesis with plasma volume expansion. METHODS: Plasma volume and the transvascular escape rate of albumin, the fraction of albumin passing from the intravascular to the extravascular space per unit of time, were assessed through the plasma disappearance curve of radioiodinated human albumin. The absolute escape rate of albumin, the total flux of albumin from intravascular to extravascular space per unit of time, was also calculated. RESULTS: Eight of the 25 patients (32%) developed marked activation of vasoconstrictor systems after paracentesis. In these patients, plasma renin activity and plasma norepinephrine concentration increased from 6.6+/-2 to 23.4+/-11 ng x ml(-1) x h(-1) and 776+/-229 to 989+/-258 pg/ml, respectively (p<0.05). No significant changes in these parameters were found in the remaining 17 patients. The activation of vasoconstrictor systems occurred in the absence of changes in plasma volume (3456+/-276 vs 3476+/-264 ml, NS), transvascular escape rate of albumin (10.4+/-1 vs 10.9+/-2%/h, NS) and absolute escape rate of albumin (9.9+/-1.9 vs 10.5+/-0.7 g/h, NS). CONCLUSIONS: These results do not support a contraction of plasma volume as the mechanism responsible for activation of vasoconstrictor systems after paracentesis. Rather, the activation of vasoconstrictor systems in the absence of changes in plasma volume suggests that paracentesis accentuates the impairment of "effective" blood volume present in cirrhotic patients with ascites.

Blood Pressure↗

Arginine vasopressin induces contraction and stimulates growth of cultured human hepatic stellate cells.

BACKGROUND & AIMS: Hepatic stellate cells (HSCs) are perisinusoidal cells believed to participate in the regulation of hepatic blood flow because of their contractile properties and presence of receptors for several vasoactive factors. It is unknown whether HSCs have receptors for vasopressin, one of the most potent endogenous vasoconstrictors. This study investigated the existence of receptors for and the effects of arginine vasopressin (AVP) on cultured human HSCs. METHODS: intracellular calcium concentration ([Ca2+]i) and cell contraction were measured in individual cells loaded with fura-2 using a morphometric method with an epifluorescence microscope coupled to a CCD imaging system (Photometrics, Tucson, AZ). AVP-specific binding was measured with [3H]AVP. Mitogen-activated protein kinase (MAPk) activity and DNA synthesis were measured by in vitro phosphorylation of myelin basic protein and [3H]thymidine incorporation, respectively. Parallel experiments were performed in vascular smooth muscle cells. RESULTS: AVP elicited a dose-dependent increase in [Ca2+]i and contraction of HSCs. Moreover, AVP increased MAPk activity, DNA synthesis, and cell number. These effects were similar to those observed in vascular smooth muscle cells and were blocked by a V1 receptor antagonist. The existence of V1 receptors was further confirmed by binding studies. CONCLUSIONS: Human HSCs have V1-vasopressin receptors that induce effects similar to those observed in vascular smooth muscle cells. AVP may play a role in the regulation of HSC function.

Animals↗

Hepatorenal syndrome.

Hepatorenal syndrome is a common complication in patients with advanced cirrhosis and ascites characterized not only by renal failure but also by marked alterations in systemic hemodynamics and vasoactive systems. Renal failure is due to a marked hypoperfusion of the kidney secondary to renal vasoconstriction. The pathogenesis of hepatorenal syndrome is not completely known but it is thought to be the extreme manifestation of the underfilling of the arterial circulation secondary to an arterial vasodilation, located mainly in the splanchnic circulation. Recently, a new definition and diagnostic criteria of hepatorenal syndrome have been proposed, which has stimulated research in this field. Prognosis of patients with hepatorenal syndrome is very poor. Liver transplantation is the only effective treatment but it is not applicable in all patients due to short survival. New therapies developed during the last few years, such as the use of systemic vasoconstrictors or transjugular intrahepatic portosystemic shunts appear promising, but their usefulness should be evaluated in prospective investigations.

Ascites↗

Management of ascites in cirrhosis.

Ascites is one of the earliest and most common complications of patients with cirrhosis. A typical circulatory dysfunction characterized by arterial vasodilation, high cardiac output and stimulation of vasoactive systems is commonly present in these patients and is associated with a poor prognosis. The treatment of ascites has been based on the combination of a low-sodium diet and the administration of diuretics. The reintroduction of paracentesis and the recent introduction of the transjugular intrahepatic portosystemic shunt (TIPS) are the most relevant innovations in the treatment of ascites during the past two decades, although controlled trials in large series of patients are needed to delineate whether TIPS is a safe and useful treatment for these patients.

Ascites↗

Practical recommendations for the treatment of ascites and its complications.

Ascites is one of the earliest and most common complications of patients with cirrhosis, and is associated with complications such as dilutional hyponatraemia, renal dysfunction and spontaneous bacterial peritonitis. The treatment of ascites has been based on the combination of a low-sodium diet and the administration of diuretics. The reintroduction of paracentesis and the recent introduction of the transjugular intrahepatic portosystemic shunt (TIPS) are the most relevant innovations in the treatment of ascites during the past 2 decades. The development of ascites is closely related to renal disturbances of functional origin, including the hepatorenal syndrome. A new definition of hepatorenal syndrome has been proposed recently and 2 different types have been defined (type I or progressive, and type III or stable). Although no effective therapy exists for this syndrome, the use of therapeutic methods (TIPS, vasoconstrictor agents, dialysis) to temporarily improve renal function and act as a 'bridge' to liver transplantation, may be of most benefit. The use of potent and safe antibiotics has improved the resolution rate and survival of patients with spontaneous bacterial peritonitis. In addition, the use of oral antibiotics will simplify the management of this condition in the near future. Finally, prophylactic antibiotic regimens represent a major step forwards in the prevention of spontaneous bacterial peritonitis in subsets of cirrhotic patients with a great risk of developing this complication.

Anti-Bacterial Agents↗

[Pyloric stenosis complicated by Wernicke-Korsakoff syndrome].

The Wernicke-Korsakoff syndrome (WKS) is a picture of oculomotor alterations, ataxia and confusion presented in chronic alcoholics. It has more rarely been described in non alcoholic patients with malnutrition. The case of a patient with ulcerous peptic disease of long evolution who consulted for a picture compatible with WKS following clinical manifestations of repeated vomiting secondary to complete pyloric stenosis is presented. The peculiarity of the picture and the convenience of prevention in malnourished patients receiving intravenous glucose sera is discussed.

Alcohol Amnestic Disorder↗

Urinary excretion of urodilatin in patients with cirrhosis.

Cirrhotic patients with ascites show increased plasma levels of natriuretic peptides from cardiac origin (i.e., atrial natriuretic peptide [ANP] and brain natriuretic peptide [BNP]). Urodilatin is a unique member of the natriuretic peptide family because it is exclusively synthesized in the kidney acting on a paracrine fashion in the regulation of sodium excretion. To investigate the renal production of urodilatin in cirrhosis and its relationship with other natriuretic peptides and sodium retention, urodilatin excretion and plasma levels of ANP were measured in 21 healthy subjects, 13 cirrhotic patients without ascites and 23 cirrhotic patients with ascites. Urine urodilatin was measured with a highly specific radioimmunoassay using a polyclonal antibody against human urodilatin. Patients with ascites had marked sodium retention (UNa 7 +/- 2 mEq/d) as compared to patients without ascites and healthy subjects (29 +/- 3 mEq/d and 34 +/- 5 mEq/d, respectively, P < .001). Patients with cirrhosis and ascites had urine urodilatin excretion similar to patients without ascites and healthy subjects (82 +/- 8 pmol/g, 95 +/- 10 pmol/g, and 89 +/- 9 pmol/ g of creatinine, respectively; not significant). In addition, immunoreactive urodilatin from cirrhotic patients with ascites and healthy subjects showed a similar chromatographic pattern. By contrast, plasma ANP levels were increased significantly in patients with ascites (29 +/- 3 fmol/mL) as compared with patients without ascites or healthy subjects (14 +/- 3 fmol/mL and 6 +/- 1 fmol/mL, respectively; P < .01). In conclusion, urine urodilatin excretion is normal in patients with cirrhosis even in the presence of marked sodium retention. The coexistence of increased ANP levels and normal urodilatin excretion suggests that in cirrhosis both natriuretic peptides are regulated independently.

Aldosterone↗

Renal and neurohormonal changes following simultaneous administration of systemic vasoconstrictors and dopamine or prostacyclin in cirrhotic patients with hepatorenal syndrome.

BACKGROUND/AIMS: Intravenous ornipressin in cirrhotic patients with hepatorenal syndrome causes marked improvement of systemic hemodynamics and suppression of plasma renin and norepinephrine but only moderate improvement of renal function. This study was designed to investigate whether these beneficial effects could be enhanced by the simultaneous administration of dopamine. The renal effects of the i.v. infusion of norepinephrine plus prostacyclin in patients with hepatorenal syndrome were also assessed. METHODS: Renal plasma flow, glomerular filtration rate, free water clearance, sodium excretion and the plasma levels of renin and norepinephrine were measured in baseline conditions and during the administration of ornipressin (6 i.u./h) and ornipressin (6 i.u./h) plus dopamine (2 micrograms/kg.min) in nine patients with hepatorenal syndrome. Five additional patients with hepatorenal syndrome were studied prior to and following the administration of norepinephrine (0.45 +/- 0.1 microgram/kg.min) and norepinephrine (0.85 +/- 0.2 microgram/kg.min) plus prostacyclin (5 ng/kg.min). RESULTS: Despite a significant increase in arterial pressure and marked suppression of plasma renin activity during ornipressin and ornipressin plus dopamine administration, no significant improvement in renal function was observed. Norepinephrine and norepinephrine plus prostacyclin also failed to increase renal perfusion and glomerular filtration rate. CONCLUSIONS: The combined administration of systemic vasoconstrictors (ornipressin or norepinephrine) and vasodilators (dopamine or prostacyclin), at the doses used in the current study and for a short period of time, does not improve renal function in cirrhotic patients with hepatorenal syndrome. The current study does not confirm a potential role for ornipressin in the treatment of hepatorenal syndrome.

Antihypertensive Agents↗

[Asymptomatic pneumoperitoneum after fiber gastroscopy].

A case of asymptomatic pneumoperitoneum after fiber gastroscopic sclerosis of bleeding gastric erosions is presented. Air bubbles in gastric curvatures without evidence of macroscopic perforation were found at laparotomy. We comment the etiologies of pneumoperitoneum without macroscopic perforation and suggest that the management of patients with asymptomatic pneumoperitoneum with normal clinical examination and blood analysis might be conservative to avoid needless laparotomies.

Aged↗

Effect of upright posture and physical exercise on endogenous neurohormonal systems in cirrhotic patients with sodium retention and normal supine plasma renin, aldosterone, and norepinephrine levels.

It is well known that sodium retention occurs in a significant proportion of patients with cirrhosis despite normal supine plasma levels of renin, aldosterone (ALDO), and norepinephrine (NE). The current study was performed to assess whether this subset of patients also present normal activity of the renin-aldosterone and sympathetic nervous systems during upright posture in sitting position and moderate physical exercise. Nine healthy controls, 14 patients with compensated cirrhosis and 10 patients with cirrhosis, ascites, sodium retention, and normal supine plasma renin activity (PRA) and ALDO and NE concentration were sequentially studied after 60 minutes in supine rest, 30 minutes in sitting position, and 30 minutes of cycloergometric exercise (3-METs). Sitting position and exercise were associated with similar stimulation of the renin-aldosterone and sympathetic nervous systems in the three groups of subjects. Consequently, cirrhotic patients with ascites showed values of PRA and plasma concentration of ALDO and NE similar to healthy subjects and patients with compensated cirrhosis during supine rest (renin: 1.4 +/- 0.3, 0.8 +/- 0.2, and 0.8 +/- 0.3 ng/mL; aldosterone: 24.3 +/- 4.7, 20.2 +/- 3.9 and 21.4 +/- 3.4 ng/dL; norepinephrine: 252 +/- 23, 250 +/- 16, and 255 +/- 23 pg/mL), sitting position (renin: 2.1 +/- 0.5, 1.1 +/- 0.3, and 1.6 +/- 0.4; aldosterone: 32.2 +/- 7.3, 23.7 +/- 5.3, and 26.2 +/- 4.5; norepinephrine: 356 +/- 38, 401 +/- 63, and 420 +/- 35), and exercise (renin: 2.9 +/- 0.8, 1.6 +/- 0.4, and 2.2 +/- 0.5; aldosterone: 43 +/- 6.4, 34.9 +/- 8.5, and 38.2 +/- 5.3; norepinephrine: 481 +/- 35, 499 +/- 54, and 534 +/- 48).(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗