Biomedical subjects

J Prieto

Publications and source records attributed to J Prieto.

At least 217 records · Page 12Linked to original sources

PubMed1995

Plasma levels of substance P in liver cirrhosis: relationship to the activation of vasopressor systems and urinary sodium excretion.

The mediators of the hyperdynamic circulation of liver cirrhosis are not well characterized. Substance P is a potent vasodilatory peptide produced by the enteric nervous system and partly cleared by the liver. In this work we have investigated the plasma levels of substance P and their relationship to the hemodynamic, neurohormonal, and renal function changes occurring in patients with cirrhosis. Seven healthy subjects (control group), 7 cirrhotic patients without ascites (group I), and 24 cirrhotic patients with ascites (group II) were studied. Cardiac output (CO), femoral blood flow (FBF), blood volume (BV), femoral arteriovenous difference of oxygen content (Ca-v O2), plasma renin activity (PRA), plasma aldosterone concentration (PAC), and plasma norepinephrine (NE) were determined. Five patients underwent trans-jugular intrahepatic porto-systemic stent shunt (TIPSS) because of refractory ascites. Immunoreactive substance P (irSP) was measured by radioimmunoassay after plasma extraction. irSP was higher in ascitic patients than in healthy controls (P < .01) and directly correlated with PRA, PAC, plasma NE, and Pugh's score and was inversely correlated with urinary sodium excretion, glomerular filtration rate, and Ca-v O2. No differences were observed between portal and peripheral vein irSP concentration. TIPSS placement induced a decrease in portal pressure and an increase in CO but circulating irSP remained unchanged. Our data show that circulating irSP is increased in decompensated cirrhotic patients and may be involved in the pathogenesis of the hemodynamic changes of cirrhosis. Alleviation of portal hypertension did not result in decreased plasma levels of this vasodilatory substance.

Aldosterone↗

PubMed1995

Taurocholate-stimulated leukotriene C4 biosynthesis and leukotriene C4-stimulated choleresis in isolated rat liver.

BACKGROUND/AIMS: Cysteinyl-containing leukotrienes seem to exert a cholestatic effect. However, leukotriene inhibitors were found to reduce bile salt efflux in isolated rat hepatocytes, suggesting a role for leukotrienes in bile flow formation. METHODS: In the isolated rat liver, the effects of two different concentrations of leukotriene C4 on bile flow and bile salt excretion are analyzed, as well as the possible effect of taurocholate on the hepatic production of cysteinyl-containing leukotrienes. RESULTS: Leukotriene C4 (0.25 fmol) increased bile salt excretion (+22.2%; P < 0.05), whereas a much higher dose (0.25 x 10(6) fmol) showed the known cholestatic effect, reducing bile salt excretion (-25.9%; P < 0.01). These dose-dependent biphasic effects were specific because they could be prevented by the simultaneous administration of cysteinyl-containing leukotriene antagonists. On the other hand, taurocholate administration induced a dose-dependent increase in biliary excretion of cysteinyl-containing leukotrienes. Furthermore, taurocholate increased messenger RNA levels of 5-lipoxygenase, a key enzyme in leukotriene biosynthesis. Taurocholate increase of hepatocyte intracellular calcium was not significant, suggesting that taurocholate effects are not mediated by stimulation of calcium metabolism. CONCLUSIONS: These results constitute evidence for the existence of a positive feedback mechanism by which bile salts stimulate the synthesis of leukotrienes that, in turn, stimulate bile salt excretion.

Animals↗

PubMed1995

Isolation and characterization of TK-deficient mutants of African swine fever virus.

African swine fever virus induces the synthesis of thymidine kinase (TK) in BHK TK-negative cells as an immediate early protein. The TK gene is not essential for growth of ASFV in cell culture and a stable viral strain deficient in TK has been isolated (E70NTKp). The genetic lesion of this ASFV TK- strain was identified by TK gene nucleotide sequencing, showing a nucleotide deletion leading to a -1 frameshift and a nonsense codon residue downstream of the deletion. The availability of this viable ASFV variant deficient in TK activity allows the insertion of foreign genes in the ASFV genome for genetic and biochemical studies.

African Swine Fever Virus↗

PubMed1995

In vivo cytotoxic T-lymphocyte induction may take place via CD8 T helper lymphocytes.

Immunization of mice with peptide constructs, consisting of a determinant recognized by T cytotoxic cells colinearly linked to a determinant recognized by T helper cells (TDc-TDh) was able to induce cytotoxic T lymphocytes in vivo. Interestingly, this induction could be achieved in the absence of adjuvant in non-depleted as well as in CD4(+)-cell-depleted BALB/c mice. In the latter case, induction took place simultaneously with the activation of CD8+ T helper cells specific for a TDh contained within the sequence of the TDc RIQRGPGRAFVTIGK from the immunodominant V3 loop of HIV1 gp120. The possible implications of these findings in HIV infection and AIDS disease are discussed.

Amino Acid Sequence↗

PubMed1995

In vivo and in vitro study of several pharmacodynamic effects of meropenem.

Several pharmacodynamic parameters are being studied and applied to the design of dosage regimens. The thigh infection model in neutropenic mice has been used in this study to investigate the in vivo postantibiotic effect (PAE) of meropenem against S. aureus, E. coli and P. aeruginosa. The sub-minimum inhibitory concentration (sub-MIC) postantibiotic effect (PA SME) of 1/2, 1/4 and 1/8 x MIC was also determined in vitro on S. aureus and E. coli after pre-exposure of these microorganisms to 10 x MIC of meropenem. The in vitro PAE was also determined. In vivo killing curves using 2 different short dosage regimens were also studied to relate the lethal effect to the time that serum levels were above the MIC. No significant in vivo and in vitro PAEs were observed. The PA SMEs were higher for S. aureus than for E. coli. The 2 short dosage regimens, in vivo, were equally effective in killing S. aureus, but not E. coli. These results suggest that the pharmacodynamics of meropenem on Gram-negative strains may need further study to elucidate the mechanisms and characteristics of these parameters. On the other hand, we need to standardize a reliable in vitro method to monitor regrowth with a good correlation with the in vivo conditions.

Animals↗

PubMed1995

Insulin-like growth factor binding proteins in arterial hypertension: relationship to left ventricular hypertrophy.

OBJECTIVE: It was reported previously that circulating insulin-like growth factor I levels are abnormally elevated in patients with essential hypertension and left ventricular hypertrophy. Tissue availability of the factor depends on the distribution of the circulating bound factor between its high- and low-molecular mass binding proteins, only the latter being able to cross the endothelium. The aim of this study was to investigate whether the presence of the different serum binding proteins is altered in patients with essential hypertension and left ventricular hypertrophy. DESIGN: The study was performed in 30 never-treated patients with essential hypertension and 30 age- and sex-matched normotensive subjects. Patients were separated into two groups according to the presence or the absence of echocardiographically determined left ventricular hypertrophy. METHODS: Plasma insulin-like growth factor I levels were determined by specific radioimmunoassay. The different molecular forms of its serum binding proteins were analysed by Western blotting using [125I]-labelled insulin-like growth factor I. A densitometric scanning of the blots was performed to analyse the quantitative relationships between the different forms of binding proteins. RESULTS: Insulin-like growth factor I levels were significantly higher in the hypertensive patients with than in the hypertensive patients without left ventricular hypertrophy or in the normotensive subjects. Compared with the normotensive subjects, both hypertensive patients subgroups exhibited increased high-molecular mass binding protein type 3 and decreased low-molecular mass binding proteins types 1 and 2. However, changes in the binding proteins were more marked in the hypertensive patients without than in the hypertensive patients with left ventricular hypertrophy. Accordingly, the ratio of low- to high-molecular mass binding proteins (an index of insulin-like growth factor I bioavailability) was higher in the hypertensive patients with than in the hypertensive patients without left ventricular hypertrophy. CONCLUSIONS: These results show that the distribution of the molecular forms of serum insulin-like growth factor binding proteins is altered in patients with essential hypertension, independently of insulin-like growth factor I levels. This suggests that regulation of the binding proteins is abnormal in essential hypertension. Whether the tissue availability of circulating insulin-like growth factor I is higher in hypertensive patients with than in hypertensive patients without left ventricular hypertrophy merits further investigation.

Adult↗

PubMed1995

Induction of sensitivity to ganciclovir in human hepatocellular carcinoma cells by adenovirus-mediated gene transfer of herpes simplex virus thymidine kinase.

We have analyzed the ability of a recombinant replication-defective adenovirus to transfer the thymidine kinase gene of herpes simplex virus (HSV-tk) into hepatocellular carcinoma (HCC) cells to confer sensitivity to ganciclovir. Three HCC cell lines (Hep3B, PLC/PRF/5, and HepG2) were efficiently infected in vitro by a recombinant adenovirus carrying lacZ reporter gene (AdCMVlacZ). Expression of HSV-tk in HCC cells infected with a recombinant adenovirus carrying HSV-tk gene (AdCMVtk) induced sensitivity to ganciclovir in a dose-dependent manner. A bystander killing effect was observed when 90% of uninfected tumor cells were mixed with only 10% of AdCMVtk-infected cells. These data show that recombinant adenoviruses are efficient vectors for transduction of drug-sensitizing genes to HCC cells in vitro. We suggest that a gene therapy approach to hepatocellular carcinoma can be established using adenoviral transfer of HSV-tk to tumor cells and subsequent administration of ganciclovir.

Adenoviridae↗

PubMed1995

Prediction of right ventricular ejection fraction by Doppler determination of right systolic time intervals.

OBJECTIVES: This study was designed to evaluate the right ventricular function by means of the determination of right ventricular systolic time intervals measured in pulmonary artery flow detected by Doppler. BACKGROUND: Left ventricular systolic time intervals have been used to evaluate left ventricular performance. There is, however, no information as to whether right ventricular systolic time intervals may be useful in the evaluation of right ventricular function. METHODS: Simultaneous measurements of right ventricular ejection fraction and Doppler determination of right systolic time intervals were made in four pigs in 47 different hemodynamic conditions that permit the modification of the right ventricular ejection fraction from 15% to 68%. The preejection time, the ratio of right preejection time to right ventricular ejection time, with and without correction by the heart rate, were correlated simultaneously to invasively determined right ventricular ejection fraction and other hemodynamic parameters, measured with a modified pulmonary artery catheter with a rapidly responding thermistor. RESULTS: There was a significant linear correlation between Doppler determination of right systolic time intervals and right ventricular ejection fraction. A similar correlation was found for preejection time (r = .80, p < .0001) and the ratio of right preejection time to right ventricular ejection time with correction by the heart rate (r = .83, p < .0001). When we used a preejection time > 70 msec as a criterion to detect a ejection fraction < 40% we found a sensitivity of 89% and specificity of 88%. A preejection time > 80 msec, as criterion of more severe ventricular disfunction (ejection fraction < 30%), displayed a sensitivity of 76% and specificity of 100%. CONCLUSION: These results show that right ventricular systolic time intervals determined by Doppler study correlate significantly with the right ventricular ejection fraction. In view of its simplicity and its accuracy in the prediction of right ventricular ejection fraction, this method may provide useful non-invasive alternative in the prediction of right ventricular ejection fraction.

Animals↗

PubMed1995

Transjugular intrahepatic portal-systemic shunt in the treatment of refractory ascites: effect on clinical, renal, humoral, and hemodynamic parameters.

Seventeen cirrhotics with refractory ascites were treated with transjugular intrahepatic portosystemic shunt (TIPS) and followed for 15.5 +/- 3.4 months. Five patients died, four within 3 months after TIPS (hepatocellular failure) and one after 22 months (cholangiocarcinoma). Six patients received transplants 1 to 10 months after the procedure. Actuarial survival at 6, 12, and 24 months was 75%, 75%, and 63%, respectively. Portosystemic venous pressure gradient decreased by 46% at 1 month and by 38% at 7 to 12 months. Eight patients presented 18 stenoses 1 to 18 months after TIPS. Twelve stenoses required balloon dilatation. Tense ascites was present before TIPS in 100% of the patients, whereas it was mild or absent in 56% at 1 month, in 66% at 3 to 6 months, in 57% at 7 to 12 months, and in 100% at 24 months after TIPS. Requirements for diuretics and paracentesis decreased after TIPS (P < .001, both). One month after TIPS, urinary and fractional sodium excretion increased (P < .001, both), plasma renin activity, plasma aldosterone (P < .005, both), and plasma norepinephrine (P < .05) decreased and cardiac output (P < .01) increased, systemic vascular resistances (P < .005) decreased, and arterial pressure did not change. Acute hepatic encephalopathy was frequent early after TIPS but was responsive to treatment and caused no long-term disability. In conclusion, TIPS is useful in the treatment of refractory ascites through lowering portal pressure and improving renal sodium excretion. This effect could be attributable to an increase in effective blood volume causing deactivation of vasopressor systems.

Adult↗

PubMed1995

Anion exchanger immunoreactivity in human salivary glands in health and Sjögren's syndrome.

Salivary gland ducts play a relevant role in saliva secretion through transport processes. Na(+)-independent chloride-bicarbonate anion exchangers (AE) may be involved in these processes by generating ion fluxes into the salivary secretion. In Sjögren's syndrome, a disorder with gland dysfunction, there might be an impaired expression of AE proteins. Here we study AE immunoreactivities in human salivary glands, both in health and in Sjögren's syndrome. Immunohistochemistry was carried out on salivary glands from normal subjects and patients with Sjögren's syndrome, using two monoclonal antibodies against AE1 and AE2. Normal salivary glands showed AE2 immunoreactivity, which was restricted to the epithelium of the ducts, with no staining at the acini. A strong positivity was seen in the basolateral portion of the striated ducts, while interlobular duct cells showed a discrete positivity at their apical pole. In salivary glands from most of the patients with Sjögren's syndrome, AE2 immunoreactivity was absent in the ducts as well as in the acini. In both normal and diseased salivary glands, AE1 immunoreactivity was only located at the erythrocyte membrane. The recently reported AE0 was discarded because no AE0 message was found in salivary glands by reverse transcription polymerase chain reaction. In conclusion, AE2 immunoreactivity is observed in the ducts of normal salivary glands, particularly in the striated ducts. AE2 immunoreactivity is virtually absent in salivary glands from patients with Sjögren's syndrome, which may reflect either a loss of AE2 after inflammatory atrophy, or a primary defect occurring in the disease.

Adult↗

PubMed1995

[Dermatomal somatosensory evoked potentials in the diagnosis of focal lesions of the spinal cord].

We studied 13 patients suffering from localized spinal cord lesions by means of somatosensory evoked potentials obtained by electrical stimulation at various dermatome levels (SEPD). The results were compared to those of somatosensory evoked potentials obtained by stimulation of the posterior tibial nerve (SEPpt), as well as to clinical and radiologic data. Structural lesions could be demonstrated in 8 patients; in 5 patients, however, X-rays were normal and/or incompatible with symptoms. We found clear correlations among clinical or radiologic data and the level of lesion indicated by SEPD in all 13 patients. In one case SEPD were abnormal 6 months in advance of the first alteration in magnetic resonance imaging. Abnormal SEPD and SEPpt results were consistent, suggesting the existence of a common central pathway to carry stimuli. SEPD should be considered a useful, reliable technique for assessing spinal cord function, especially when no structural lesion can be demonstrated or when spinal injury is doubtful or when several segments are involved.

Adolescent↗

PubMed1995