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Biomedical subjects

J Prieto

Publications and source records attributed to J Prieto.

At least 181 records · Page 10Linked to original sources
PubMed1997

Low doses of insulin-like growth factor-I improve nitrogen retention and food efficiency in rats with early cirrhosis.

BACKGROUND/AIMS: In order to ascertain whether malnutrition is an early-onset feature of liver cirrhosis and whether the anabolic hormone insulin-like growth factor I (IGF-I) could be useful in the treatment of this complication, we analyzed the nutritional alterations present in rats with early-stage liver cirrhosis and the effects of IGF-I on nutritional parameters in these animals. METHODS: After a 24 h fast, a 15N-enriched diet was administered for 5 days to normal control rats and to cirrhotic rats receiving subcutaneous injections of vehicle (Group 1) or IGF-I, 2 micrograms.100 g bw-1.day-1, (Group 2) during the 5 experimental days. 15N, a stable N isotope, was measured in biological samples by mass spectrometry. RESULTS: Compared with control rats, Group 1 animals showed significant reductions in N intake and food efficiency (p < 0.05, both). In addition, the weight of the gastrocnemius muscle, its total N content and the dietary N content of this muscle were significantly lower in Group 1 than in control animals (p < 0.05, all). In rats from Group 2, mean values of N intake, food efficiency, gastrocnemius N content and the amount of dietary N incorporated into this muscle were similar to those in control rats, and (with the exception of gastrocnemius N total content) significantly higher than those in non-treated cirrhotic rats (p < 0.05, all). CONCLUSIONS: A variety of nutritional disturbances were detected in rats from the early stages of liver cirrhosis. Low doses of IGF-I were found to reverse most of these changes. These results stimulate further studies to determine whether IGF-I might be useful in the correction of the malnutrition present in patients with liver cirrhosis.

Acute Disease↗
PubMed1997

Therapeutic vaccination of woodchucks against chronic woodchuck hepatitis virus infection.

BACKGROUND/AIMS: Therapeutic vaccination is a new approach to treat patients with chronic hepatitis B virus infection. We have used the woodchuck model to examine the efficacy and safety of this approach. METHODS: Seven woodchucks chronically infected with woodchuck hepatitis virus were immunized with surface antigen from this virus, purified from plasma, in conjunction with a peptide named FIS (encompassing amino acids 106-118: FISEAIIHVLHSR from sperm whale myoglobin), which is recognized by T helper lymphocytes. As controls, two woodchucks chronically infected with woodchuck hepatitis virus were immunized: one with FIS only and the other with surface antigen only. RESULTS: Co-immunization with surface antigen and FIS, but not with FIS or surface antigen alone, induced anti-surface antibodies in 7/7 immunized woodchucks. In the two woodchucks in which the highest titer of anti-surface antibody was elicited, severe liver damage was observed: one died of fulminant hepatitis and the other became seriously ill with hepatic injury and had to be sacrificed. CONCLUSIONS: Co-immunization of chronically infected woodchucks with surface antigen and a peptide recognized by T helper cells produces a good anti-surface antibody response. However, this strategy needs to be optimized before its implementation in humans. Although our experiments are not strictly comparable to vaccination of chronically hepatitis B virus-infected patients with recombinant or plasma-derived vaccines, we believe that precautions should be taken to avoid the risk of severe liver injury when immunizing hepatitis B virus carriers.

Amino Acid Sequence↗
PubMed1997

Enhanced urinary excretion of cGMP in liver cirrhosis. Relationship to hemodynamic changes, neurohormonal activation, and urinary sodium excretion.

Cyclic guanosine monophosphate (cGMP) has been proposed to mediate peripheral arterial vasodilation in liver cirrhosis. Nitric oxide and natriuretic peptides are the main signals for cGMP generation. Variation in urinary cGMP excretion parallels changes in plasma cGMP levels. Our aim was to determine urinary excretion of cGMP (UcGMPV) and to investigate its relationship to systemic hemodynamics, neurohumoral activity and renal sodium excretion in cirrhosis. Urinary excretion of cGMP was measured in 19 healthy subjects and 20 patients with alcoholic cirrhosis. Systemic hemodynamic parameters, blood volume (BV), plasma atrial natriuretic factor (ANF), and the endothelium-dependent vasodilator substance P (SP) were determined in all patients and in five healthy subjects. Urinary cGMPV was higher in the group of patients (736 pg/min; 50-3229 pg/min) than in controls (126 pg/min; 0-1657 pg/min) (P < 0.01). In addition, UcGMPV inversely correlated with the systemic vascular resistance and directly with cardiac output, blood volume, SP, ANF, and Pugh's score. By Cox regression analysis, only systemic vascular resistance remained inversely associated with UcGMPV. In conclusion, urinary cGMP excretion is increased in cirrhosis. It is suggested that increased cGMP generation may be related to the hyperkinetic circulation in human cirrhosis.

Atrial Natriuretic Factor↗
PubMed1997

Impaired intestinal sugar transport in cirrhotic rats: correction by low doses of insulin-like growth factor I.

BACKGROUND & AIMS: Malnutrition is a complication of liver cirrhosis accompanied by reduced insulin-like growth factor I (IGF-I) availability. The aim of this study was to analyze the effect of IGF-I on intestinal D-galactose absorption in cirrhotic rats. METHODS: IGF-I (2 micrograms.100 g body wt-1.day-1) or saline were given for 14 days to rats in whom cirrhosis was induced with CCl4. Galactose transport and sodium-glucose/galactose-ligand transporter 1 (SGLT-1) expression were assessed in jejunal rings and in brush border membrane vesicles (BBMVs). RESULTS: Compared with that in controls, galactose transport in everted jejunal rings was significantly reduced in cirrhotic rats but showed normal values after IGF-I treatment. The kinetic study of D-galactose uptake by BBMVs showed decreased maximal velocity (Vmax) and diminished transporter affinity in cirrhotic rats. These kinetic parameters reverted to normal after IGF-I treatment. Microvilli were significantly elongated in cirrhotic rats but of normal size in the IGF-I-treated group. The expression of SGLT-1 on BBMVs (Western blot) and on the luminal membrane of enterocytes (immunohistochemistry) was not reduced in cirrhotic animals compared with controls or IGF-treated cirrhotic rats. CONCLUSIONS: Intestinal sugar transport is disturbed in experimental cirrhosis, and this alteration is corrected by IGF-I.

Alanine Transaminase↗
PubMed1997

Viremia after one month of interferon therapy predicts treatment outcome in patients with chronic hepatitis C.

BACKGROUND & AIMS: In chronic hepatitis C, interferon alfa induces sustained remission in less than 30% of treated patients. The aim of this study is to analyze viral status early after initiation interferon therapy as a predictor of treatment outcome. METHODS: One hundred eighty-one patients with chronic hepatitis C who had been treated with interferon alfa for 12 months (median follow-up, 49 months) were studied. Viremia and aminotransferase levels at the first and third months of therapy as well as 10 pretreatment variables were assessed as potential independent predictors of sustained response to treatment. RESULTS: Sustained response occurred in 51 patients (28%). At month 1 of treatment, viral persistence accurately predicted nonresponse (predictive value, 95.3; 95% confidence interval, 86.0-98.8; P < 0.0001). Independent predictors of sustained response were undetectable viremia at the first month of therapy (P < 0.001), undetectable viremia at the third month (P < 0.001), younger age (P = 0.006), nonsporadic infection (P = 0.012), and higher pretreatment aspartate aminotransferase levels (P = 0.032). In patients who cleared HCV RNA at month 1 of therapy, the predicted probability of sustained response averaged 70% for those younger than 30 years and diminished by 10% for each decade of age. CONCLUSIONS: Failure to clear HCV RNA at month 1 of treatment is strongly and independently associated with a very low probability of a sustained response to interferon.

Adolescent↗
PubMed1997

Hepatoprotective effects of insulin-like growth factor I in rats with carbon tetrachloride-induced cirrhosis.

BACKGROUND & AIMS: Bioavailability of insulin-like growth factor (IGF-I) is reduced in liver cirrhosis. The aim of this study was to analyze the effect of IGF-I on liver histopathology and function in experimental cirrhosis. METHODS: Rats received CCl4 inhalations for 11 or 30 weeks (protocols 1 and 2, respectively) and were treated with 2 microg x 100 g body wt(-1) x day(-1) IGF-I (group CI + IGF) or saline (group CI) on weeks 13 and 14 (protocol 1) or on weeks 28-30 (protocol 2). Normal rats were studied in parallel. RESULTS: Serum albumin and total protein levels were reduced in CI but not in CI + IGF rats compared with normal rats. Clotting factors II, VII, and X were significantly greater in CI + IGF than in CI rats. Liver lipid peroxidation products were significantly increased in CI but not in CI + IGF rats, and liver fibrosis was less pronounced in CI + IGF than in CI animals. The activities of antioxidant enzymes and mitochondrial transmembrane potential were reduced compared with normal animals in CI but not in CI + IGF rats. CONCLUSIONS: IGF-I improves liver function and reduces oxidative liver damage and fibrosis in rats with compensated or advanced liver cirrhosis. Improved mitochondrial function could play a role in the hepatoprotective effect of this hormone.

Animals↗
PubMed1997

Meropenem-induced alteration of the susceptibility of Escherichia coli and Staphylococcus aureus to the bactericidal activity of human polymorphonuclear leucocytes.

The analysis of the interaction between antimicrobials and phagocytosis in vitro provides information additional to standard MIC and MBC estimations in predicting in-vivo efficacy. This study investigated the effects of meropenem, a newly available carbapenem, on the activities of human neutrophils against Escherichia coli and Staphylococcus aureus. The results were compared with those obtained with imipenem. Pretreatment of E. coli and S. aureus with meropenem and imipenem sensitized the bacteria to leucocytic killing. In the presence of antibiotics, opsonophagocytic killing of E. coli, but not S. aureus, was synergistically enhanced.

Blood Bactericidal Activity↗
PubMed1997

Suspicion of quinolone active metabolite following discrepancy between predicted and experimental urine bactericidal activities.

The prediction of urine antibacterial activity from pharmacological and microbiological parameters was assessed by using experimental urine levels and urine bactericidal titers determined up to 72 h after a 400-mg single dose of two quinolones in a phase I study. The area under the bactericidal curve (AUBC) was accurately predicted for norfloxacin but significantly (P < 0.001) underestimated for rufloxacin (actual value was four times higher than the predicted value against Escherichia coli and two times higher against Staphylococcus aureus). In vitro susceptibility differences between the two strains predicted the ex vivo AUBC differences for norfloxacin but not for rufloxacin, where ex vivo differences were greater than expected. Urine bactericidal titers for up to 72 h were accurately predicted for norfloxacin against E. coli and S. aureus and for rufloxacin against S. aureus, but experimental activity for up to 48 h was four times higher (P < 0.001) than the predicted activity for rufloxacin against E. coli. In the case of norfloxacin, the duration of adequate urine antibacterial activity against S. aureus was overestimated. Inaccurate estimations of ex vivo antibacterial activity of a suspected active metabolite (as with rufloxacin) when an adequate cutoff is not established may have dosing implications.

Anti-Infective Agents↗
PubMed1997

Pharmacodynamic effects of amoxicillin versus cefotaxime against penicillin-susceptible and penicillin-resistant pneumococcal strains: a phase I study.

Serum bactericidal activity against a penicillin-susceptible strain and a penicillin-resistant strain of Streptococcus pneumoniae (amoxicillin and cefotaxime MICs, 0.001 and 1 microg/ml, respectively, and MBCs, 0.01 and 2 microg/ml, respectively) was measured in 12 healthy volunteers who each received an oral 875-mg dose of amoxicillin and an intramuscular 1-g dose of cefotaxime in a crossover fashion. The areas under the bactericidal activity-time curves for the two strains were found to be similar for both antibiotics despite the significantly higher (P < 0.002) AUC/MIC and peak level/MIC values for cefotaxime.

Adult↗
PubMed1997

In vitro assessment of the effect of clavulanic acid at concentrations achieved in human serum on the bactericidal activity of amoxicillin at physiological concentrations against Staphylococcus aureus: implications for dosage regimens.

The effects on Staphylococcus aureus viability and beta-lactamase activity of concentrations that simulated those in human serum after a combined dose of 875 mg of amoxicillin and 125 mg of clavulanic acid were studied in an in vitro pharmacodynamic model. Six hours of preexposure to concentrations of the amoxicillin-clavulanic acid combination that were higher than the amoxicillin-clavulanic acid MIC led to a reduction of the initial inoculum of >90% and to a significant decrease of beta-lactamase activity versus those of the control even from 6 h, when concentrations were subinhibitory. The postantibiotic effect and post-beta-lactamase inhibitor effect contributed to these results.

Amoxicillin↗
PubMed1997

[Usefulness of the angiographic examination of the left internal mammary artery in patients candidates for coronary bypass surgery].

BACKGROUND AND OBJECTIVE: The usefulness of preoperative angiographic evaluation of the internal mammary artery (IMA) is controversial. The aim of this study is to evaluate the problem by a basic cost-benefit analysis. METHODS: One hundred and twenty-one patients whose coronary findings (left main disease and/or severe stenosis of the left anterior descending artery) made use of the IMA as a bypass graft a consideration were studied. The IMA was cannulated by the same right Judkins catheter used in the coronarography; the specific catheter was only used if the cannulation was not successful with the right Judkins. We measured the time it took for a good angiography of the IMA to be obtained; the anatomy and the size for each IMA were studied and compared with the size of the left anterior descending artery. RESULTS: An optimal angiographic picture of the IMA was obtained in 119 cases (98.3%); a specific catheter was used only in 3 patients. The mean of the time employed was 170 seconds (8-900 s) and no complications were related to IMA cannulations. Angiography findings relevant to any planned surgery were demonstrated in 15 patients (12%): large proximal branches (10); occlusion stenosis or a caliber insufficient for IMA (3); and occlusion or proximal subclavian stenosis (2). CONCLUSIONS: We have observed that the relation between the cost and the obtained information is adequate to warrant its performance, because angiographic findings relevant to planned surgery can be very important, even though they are fairly infrequent. Moreover, these findings can be achieved rapidly without additional cost.

Coronary Angiography↗
PubMed1997

Cementless total hip arthroplasty in patients with advanced avascular necrosis.

We retrospectively reviewed a series of 40 cementless total hip arthroplasties in 31 patients with advanced avascular necrosis. The average follow-up was 58 months (range, 24 months to 108 months). The clinical failure rate was 20% (8 hips in 7 patients). Three of 7 threaded cups failed, and 2 of 32 porous coated hemispherical cups failed. Of the 5 stem failures, 1 was due to technical error, and 4 were well ingrown porous stems that succumbed to progressive osteolysis.

Adult↗
PubMed1997

[High prevalence without reactivation of herpes virus 6 in subjects with chronic fatigue syndrome].

INTRODUCTION: Chronic fatigue syndrome (CFS) is a disorder of unknown etiology. Some viruses have been associated with CFS etiology, specially herpesviruses, enteroviruses and retroviruses. Some studies suggest an association between human herpesvirus-6 (HHV-6) and CFS. In order to know if there is an active HHV-6 infection in CFS patients we studied the immunologic and virologic status of HHV-6. MATERIALS AND METHODS: Twenty patients with CFS were studied. IgG and IgM anti HHV-6 were determined by indirect immunofluorescence assay. DNA from serum and peripheral blood mononuclear cells (PBMC) were studied by dot- and Southern-blotting and nested-PCR to detect HHV-6 DNA. HHV-6 RNA from PBMC were amplified by RT(retrotranscription)-PCR. RESULTS: Ten patients (50%) had IgG anti-HHV-6 in serum but none had IgM anti-HHV-6. Dot-blotting of DNA from 200 microliters of serum and Southern-blotting of 10 micrograms of PBMC DNA were negative. Nested-PCR from sera were negative. Nested-PCR with 1 microgram PBMC DNA were positive in 8 out 20 (40%) and with 5 micrograms PBMC DNA were positive in 16 out of 20 (80%). No viral RNA were detected in PBMC. CONCLUSIONS: There is a high proportion of CFS patients infected with HHV-6 but with low viral load. Results do not support HHV-6 reactivation in CFS patients.

Adult↗
PubMed1997

[Prevalence of hypercoagulation conditions in patients with thrombosis in Northern Navarra].

BACKGROUND: To determine the prevalence of hypercoagulability states in patients with thromboembolic disease in Septentrional Navarra. PATIENTS AND METHODS: 74 patients were studied (13 female, mean age [+/- SD] 43.5 +/- 13.9 years, range 22-81) with: deep venous thrombosis (DVT) with or without pulmonary embolism (PE) in 15 patients; ischemic stroke (IS) in 20 patients and; myocardial infarction (MI) in 39 patients. Antithrombin III, C protein (CP), plasminogen, plasminogen activator inhibitor (PAI), total S protein (TSP), free S protein (FSP), lupus anticoagulant (LA) and anticardiolipin antibodies (ACA) type IgG were determined in all patients. RESULTS: The prevalence of hypercoagulability state was 27% in patients with thromboembolic disease; 26.6% in patients with PE (20% with ACA and 6.6% with CP deficiency); 30% in patients with IS (15% with ACA, CP deficiency in 5%, FSP deficiency in 5%, and PAI raising in 10%) and in the 25.6% of patients with MI (15.3% with ACA, 2.5% with CP deficiency, 2.5% with TSP and FSP deficiency and PAI raising in the 7.6%). CONCLUSIONS: In Septentrional Navarra population with thromboembolic disease the presence of hypercoagulable states is high. In our study, the most common hypercoagulable state was the presence of ACA, followed by PAI raising and by the CP deficiency.

Adult↗
PubMed1996

Further insights on the inhibition of HIV type 1 infection in vitro by CD4-modified synthetic peptides containing phenylalanine.

Phenylalanine-containing peptides from CD4 were synthesized on the basis of chemical similarity with active CD4(81-92)-benzylated peptides. Systematic replacement of amino acids of these peptides bearing the benzyl group by phenylalanine, afforded several peptides that were able to block the binding of gp120 to CD4 and to inhibit HIV-induced syncytium formation. These experiments showed that substitution of residues 81 and 85 by phenylalanine was the most important for activity. Following optimization of the length of phenylalanine-substituted peptides it was found that FYICFVED and FYICFVEDE were the most active. Their IC50 for the inhibition of syncytium formation was around 1.2-1.6 microM. This activity is at least 30 times higher than that of the parent peptide FYIFFVEDQKEEDD previously reported (Lasarte et al., J Acquir Immune Defic Syndr 1994;7:129-134). Binding competition experiments with two different anti-peptide antisera recognizing the V3 region of gp120 and FYICFVEDE, show that the active peptides bind to V3 or to a sterically near region of V3. None of the active peptides was toxic to cells in vitro. The enhanced activity and simplicity of these new phenylalanine-substituted CD4 peptides might be a good starting point for the development of mimotopes of potential use for the treatment of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Anticardiolipin antibodies in chronic hepatitis C: implication of hepatitis C virus as the cause of the antiphospholipid syndrome.

Antiphospholipid antibodies are a type of autoantibodies that have been implicated in the occurrence of thrombocytopenia and thrombotic events and have been described in autoimmune disorders and diverse viral diseases. In this study anticardiolipin antibodies (immunoglobulin G [IgG] isotype) were determined in serum from 100 patients with chronic hepatitis C and 52 healthy controls. In addition, hepatitis C virus (HCV) markers (anti-HCV and HCV RNA) were investigated in 73 patients with thrombotic disorders and no clinical evidence of liver disease; of these patients 37 cases tested negatively for anticardiolipin antibodies and 36 positively. Anticardiolipin test was positive more frequently (22%) in the group of patients with chronic hepatitis C than in healthy controls (1.9%; P < .001). Using conditional logistic-regression analysis we found that in hepatitis C patients the presence of thrombocytopenia, portal hypertension and the existence of prior thrombotic episodes were significantly related to positivity for anticardiolipin antibodies (P < .05 in all cases). In patients with no evidence of liver disease and a history of thrombotic events, hepatitis C markers were absent in all cases who tested negatively for anticardiolipin antibodies (n = 37), but were present in 16.7% of those positive for anticardiolipin (n = 36) (P = .01). In conclusion, anticardiolipin antibodies are frequently found in patients with chronic hepatitis C and in these patients they may be implicated in the occurrence of thrombosis and in the development of thrombocytopenia. Occult HCV infection is present in a significant proportion of patients with thrombotic disorders and positive for anticardiolipin (the antiphospholipid syndrome).

Adult↗