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Biomedical subjects

I Herrero

Publications and source records attributed to I Herrero.

At least 19 recordsLinked to original sources
PubMed2004

Dynamic color Doppler sonography of intestinal wall in patients with Crohn disease compared with healthy subjects.

OBJECTIVE: Chronic inflammatory bowel diseases are characterized by inflammatory hyperperfusion of the intestinal wall in affected bowel segments. We applied a novel method to quantify color Doppler signals dynamically along a complete heart cycle inside the bowel wall. The aim was to describe bowel wall perfusion in Crohn disease patients in comparison with healthy probands and to compare a conventional activity index (Pediatric Crohn Disease Activity Index) with perfusion measurements as an indicator of inflammatory activity. METHOD: Color Doppler sonographic videos of bowel wall perfusion from 34 healthy children (aged 5 to 18 years) and from 14 patients with Crohn disease (aged 8.2 to 15.9 years) were recorded under defined conditions. Perfusion signals (color hue, color area) were automatically measured inside the bowel wall. Specific tissue perfusion was calculated as mean flow velocity of a region of interest during one full heart cycle. Bowel wall perfusion was compared using the Pediatric Crohn Disease Activity Index in 12 patients. RESULTS: Specific bowel wall perfusion was significantly elevated in bowel segments of Crohn disease patients compared with healthy subjects (P < 0.001). Specific flow in small bowel was 0.025 cm/s in healthy probands and 0.095 cm/s in patients with Crohn disease, whereas large bowel wall perfusion of 0.012 cm/s in healthy probands clearly differed from 0.082 cm/s in patients with Crohn disease. No differences of perfusion between moderate and high Pediatric Crohn Disease Activity Index levels could be demonstrated despite a weak significant overall correlation. CONCLUSION: The new method of dynamic, automatic noninvasive perfusion quantification is useful to describe local inflammatory activity in bowel segments affected by Crohn disease and adds new information to activity evaluation by Pediatric Crohn Disease Activity Index. Specific wall perfusion in intestines of Crohn patients is significantly elevated and reaches up to sevenfold intensity compared with healthy subjects.

Adolescent↗
PubMed2001

The enhancement of endogenous cAMP with pituitary adenylate cyclase-activating polypeptide protects rat kidney against ischemia through the modulation of inflammatory response.

BACKGROUND: Cyclic nucleotide analogue administration improves ischemia-reperfusion damage in several organs. The neuropeptide pituitary adenylate cyclase-activating polypeptide, PACAP-38, is a potent stimulus to enhance cellular cAMP levels. This study tested the protective effect of enhancing endogenous cAMP levels by PACAP-38 in a model of warm renal ischemia. METHODS: Sprague-Dawley rats underwent 40 min of bilateral warm renal ischemia. PACAP-38 continuous infusion began either before ischemia or at 6 hr or 18 hr after ischemia. A mini-osmotic pump infused PACAP-38 throughout 7 days of follow-up. Groups were constructed with sham, ischemic control, and dibutyryl cAMP treated animals, and four PACAP-38 treatment groups, using 16 pmol/hr or 160 pmol/hr of the compound, or delaying its administration by 6 hr or 18 hr after ischemia. Renal function was assessed by means of serum creatinine levels on days 1, 2, 3, and 7 after ischemia. Conventional histology was performed on day 7. Renal myeloperoxidase (MPO) activity, infiltrating CD45+ cells, plasma and tissue cAMP, and serum IL-6 were measured. RESULTS: Continuous administration of the high concentration of PACAP-38 ameliorated renal function and morphologic abnormalities induced by warm ischemia. Treatment with dibutyryl cAMP produced morphologic protection but only partial functional effect on the ischemic kidney. A 6-hour delay in the administration of the compound after ischemia offered similar protective effect, whereas an 18-hr delay did not. The neuropeptide clearly increased circulating cAMP after ischemia but not cAMP in renal tissue. PACAP-38 increased circulating IL-6, and minimized renal inflammatory cell infiltration induced by ischemia-reperfusion injury, as evidenced by a reduction of MPO activity and the number of CD45+ cells in ischemic renal tissue. CONCLUSIONS: Enhancement of endogenous circulating cAMP with PACAP-38 modulates postischemic inflammatory response and strongly protects from ischemic acute renal failure, even when administration is delayed for 6 hr after injury.

Acute Kidney Injury↗
PubMed2001

HIV-1 genetic diversity in Galicia Spain: BG intersubtype recombinant viruses circulating among injecting drug users.

BACKGROUND: The HIV-1 epidemics in Western Europe are dominated by B subtype viruses. Non-B subtype is largely restricted to individuals infected outside of Europe and to their direct contacts and is generally acquired by the heterosexual route. METHODS: Protease and a segment of reverse transcriptase were amplified and sequenced from plasma RNA in 451 individuals from seven cities of Galicia, north-western Spain. Subtype sequence homologies were determined using the BLAST algorithm. Non-B sequences were examined by phylogenetic analysis and intersubtype recombination by bootscanning. The env V3 region was analysed in all non-B and in 38 B subtype viruses. RESULTS: Ten different non-B genetic forms were identified in 20 (4.4%) individuals. Subtypes were concordant between pol and V3 in five viruses; 14 (70%) infections were with intersubtype recombinant viruses, and one individual had a dual B+G infection. Seven recombinant viruses were phylogenetically related to five reported recombinant forms. Three non-recombinant G and six recombinant BG viruses formed a monophyletic cluster for pol. All but three individuals with non-B infections were native Spanish. Only 6 of 16 individuals referred to sexual contacts with sub-Saharan Africans. Twelve (60%) non-B subtype infections, including all with G and BG viruses, were in injecting drug users (IDU). CONCLUSIONS: Non-B subtype viruses were identified in 4.4%, with a high diversity of genetic forms, including 70% infections with intersubtype recombinant viruses. The majority of individuals with non-B infections were IDU, most of them without known contacts with non-European sources, and among whom BG recombinant viruses are circulating.

Adult↗
PubMed2000

Influence of nephron mass in development of chronic renal failure after prolonged warm renal ischemia.

The present study examined the long-term consequences of warm renal ischemia (WRI) with or without renal ablation. Male Sprague-Dawley rats (250-300 g) were subjected to 60 min of complete WRI by pedicle clamping and then followed for 52 wk. Animals were organized into four groups: rats in which both kidneys were subjected to warm ischemia (2WIK); rats with left WRI and right nephrectomy (1WIK); uninephrectomized rats with a left nonischemic kidney (1NK); and sham-operated rats (2NK). Additional animals were studied at 24 h, 7 days, and 16 and 32 wk. In the first week after WRI, rats from the 2WIK and 1WIK groups displayed a similar degree of acute renal damage. After recovering from acute renal failure, 1WIK rats developed progressive and severe proteinuria, whereas it was mild in the 2WIK group, as well as in the 1NK and 2NK groups. Only animals from the 1WIK group developed severe chronic renal failure, glomerulosclerosis, interstitial fibrosis, and upregulation of transforming growth factor-beta(1) (TGF-beta(1)) gene, which was associated with increased TGF-beta(1) protein expression in tubular epithelial cells, arterioles, and in areas of mononuclear interstitial cell infiltrate. On the contrary, long-term renal TGF-beta(1) expression, function, and histology were similar in 2WIK and 2NK rats. The present study shows that prolonged bilateral WRI, when both kidneys are retained in place, induces very mild long-term renal lesions as opposed to the severe renal scarring observed when WRI is combined with contralateral nephrectomy.

Acute Kidney Injury↗
PubMed1999

Presynaptic group 1 metabotropic glutamate receptors may contribute to the expression of long-term potentiation in the hippocampal CA1 region.

In this study, we investigated the possible contribution of presynaptic group 1 metabotropic glutamate receptor activation to changes in synaptic efficacy by means of analysis of glutamate release in hippocampal synaptosomes. Data were interpreted in the context of group 1 metabotropic glutamate receptor involvement in synaptic plasticity in the CA1 region of freely moving rats. In synaptosomes, 3,5-dihydroxyphenylglycine enhanced diacylglycerol formation and facilitated vesicular Ca(2+)-dependent glutamate release, whereas trans-azetidine-2,4-dicarboxylic acid had no effect on these processes. Trans-azetidine-2,4-dicarboxylic acid enhanced glutamate release, but in a Ca(2+)-independent manner. This effect was mimicked by the L-glutamate uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid. (R,S)-alpha-Methyl-4-carboxyphenylglycine blocked the effects of 3,5-dihydroxyphenylglycine, but not trans-azetidine-2,4-dicarboxylic acid in synaptosomes. Short-term potentiation (100 Hz, three bursts of 10 stimuli, 0.1 ms stimulus duration, 10 s interburst interval) was induced in the CA1 region in vivo. The metabotropic glutamate receptor agonist 1S,3R-aminocyclopentane-2,3-dicarboxylic acid, or the group 1 metabotropic glutamate receptor agonists, 3,5-dihydroxyphenylglycine and trans-azetidine-2,4-dicarboxylic acid, dose-dependently facilitated short-term potentiation into long-term potentiation, which lasted > 24 h. The facilitation was inhibited by the metabotropic glutamate receptor antagonist, (R,S)-alpha-methyl-4-carboxyphenylglycine, and the group 1 metabotropic glutamate receptor antagonist, (S)-4-carboxy-phenylglycine, but not by the group 2 metabotropic glutamate receptor antagonist, (R,S)-alpha-methylserine-O-phosphate monophenyl ester. L-Trans-pyrrolidine-2,4-dicarboxylic acid dose-dependently facilitated short-term potentiation into long-term potentiation, which lasted < 4 h. These data suggest that activation of group 1 metabotropic glutamate receptors results in presynaptic modulation of glutamate release. This effect may contribute to group 1 metabotropic glutamate modulation of the expression of long-term potentiation in vivo.

Animals↗
PubMed1999

Long-term protective effect of UR-12670 after warm renal ischemia in uninephrectomized rats.

BACKGROUND: The phospholipid platelet-activating factor (PAF) participates in the pathogenesis of renal ischemia/reperfusion injury, and in vitro, it induces synthesis of extracellular matrix proteins by mesangial and tubular epithelial cells. This study investigated the long-term effects of the potent orally active PAF antagonist UR-12670 in warm ischemic uninephrectomized rats, which was given according to different therapeutic schedules. METHODS: Uninephrectomized male Sprague-Dawley rats were divided into five groups and were followed for 52 weeks: rats without ischemia (SK); ischemic kidney for 60 minutes (SIK); ischemic kidney and UR-12670 from 0 to the 7th day (UR 0-7); ischemic kidney and UR-12670 from day 0 to 52 weeks (UR 0-E); and ischemic kidney and UR-12670 from day 8 to week 52 (UR 8-E). Two more groups (ischemic and UR treated) served to evaluate the UR-12670-protective effect on ischemic acute renal failure at one week. RESULTS: UR-12670 administration exerted functional and morphological protection against post-ischemic acute renal failure. The ischemic untreated (SIK) group developed progressive proteinuria from week 12. The onset of proteinuria in ischemic UR-12670-treated groups was delayed to the 24th week, and it was significantly lower than in SIK group throughout the study. Only SIK and ischemic-treated UR 0-7 rats presented with chronic renal failure, as shown by creatinine, creatinine clearance, glomerular filtration rate (GFR), and renal plasma flow (GFR 52 weeks: SK, 2525 +/- 267; SIK, 992 +/- 149; UR 0-7, 1551 +/- 385 microliter/min). Kidneys from the short-term treated group (UR 0-7) showed a reduction of glomerulosclerosis (SK, 14.4 +/- 3.7; SIK, 75.7 +/- 7.7; UR 0-7, 41. 5 +/- 8.5%) and vascular myointimal hyperplasia, but the tubulointerstitial damage (tubulointerstitial score: SK, 0.2 +/- 0. 2; SIK, 4.4 +/- 0.5; UR 0-7, 3.7 +/- 0.7) was similar to that in the ischemic untreated group. Long-term ischemic treated rats (UR 0-E, UR 8-E) did not develop chronic renal failure (GFR: UR 0-E, 2059 +/- 314; UR 8-E, 2410 +/- 208 microliter/min). In these groups, glomerulosclerosis (UR 0-E, 32.8 +/- 5.8; UR 8-E, 24.3 +/- 3.0%), tubulointerstitial damage (tubulointerstitial score: UR 0-E, 2.1 +/- 0.5; UR 8-E, 1.9 +/- 0.3) and vascular myointimal hyperplasia were significantly lower than in the ischemic untreated group. By in situ hybridization, an increase of transforming growth factor-beta1 mRNA expression in glomerular and tubular cells was observed in ischemic untreated and ischemic treated UR 0-7 rats. UR-12670 long-term treated rats showed a clear reduction of transforming growth factor-beta1 mRNA-positive glomerular cells. CONCLUSION: The chronic administration of the PAF antagonist UR-12670 attenuates the long-term effects of ischemia-reperfusion injury in uninephrectomized rats. The beneficial effect of this agent, even when given beyond the initial ischemia/reperfusion injury, suggests that PAF plays a role in the mechanisms of progression to late renal damage in this model.

Acute Kidney Injury↗
PubMed1999

Prevention of cold ischaemia-reperfusion injury by an endothelin receptor antagonist in experimental renal transplantation.

BACKGROUND: Endothelin (ET) is known to play a role in the pathogenesis of warm ischaemic renal damage, however, little is known about its involvement in renal cold ischaemia. This study was designed to investigate the response of ET after kidney cold ischaemia, and to assess the potential protective effect of bosentan, a dual, non-selective ET(A)/ET(B) receptor antagonist, against cold ischaemia reperfusion injury in a rat model of syngeneic renal transplantation. METHODS: Kidneys from Lewis rats were transplanted, either immediately or after 5 h of cold preservation. After 48 h, contralateral nephrectomy was performed. Rats were organized into three groups: Tr-NoISC, no cold ischaemia; Tr-ISC, 5 h cold ischaemia; and Tr-BOS, 5 h cold ischaemia plus bosentan (100 mg/kg/day, from the day before transplantation until the seventh day post-transplantation). On day 7, plasma and tissue immunoreactive ET (irET), as well as ET mRNA tissue expression, were evaluated. Renal function was measured by means of serum creatinine on days 3, 4, 5 and 7, and by creatinine clearance on day 7. Conventional histology was performed. RESULTS: The ischaemic group had significantly higher plasma irET levels than the non-ischaemic group and significantly lower levels than the bosentan group. Tissue irET levels and ET mRNA expression were similar in the ischaemic and bosentan groups and were higher than in the non-ischaemic group. Throughout the follow-up, serum creatinine was significantly higher in the ischaemic group than in the bosentan group. Moreover, creatinine decreased rapidly in the bosentan group after nephrectomy, whereas it continued to increase for 48 h in the ischaemic group. Kidneys from the ischaemic group showed a higher degree of tubular-cell necrosis and epithelial-cell detachment than kidneys from the bosentan group. CONCLUSIONS: We conclude that cold ischaemia and preservation damage induces an increase in renal ET mRNA and irET expression in the reperfusion phase, contributing both to the deterioration of renal function and to tubular necrosis. Bosentan is effective in protecting kidneys from this cold ischaemia reperfusion damage. Non-selective ET(A)/ET(B) receptor antagonists might be potentially useful in clinical renal transplantation.

Animals↗
PubMed1998

Functional switch from facilitation to inhibition in the control of glutamate release by metabotropic glutamate receptors.

We have investigated the role of metabotropic glutamate receptors linked to phosphoinositide hydrolysis in the control of glutamate release in cerebrocortical nerve terminals. The activation of these receptors with the agonist 3,5-dihydroxyphenylglycine enhanced intra-synaptosomal diacylglycerol and facilitated both the depolarization-induced increase in the cytosolic free Ca2+ concentration and the release of glutamate. However, 5 min after receptor activation, a second stimulation of the pathway with the agonist failed to produce diacylglycerol and to facilitate glutamate release. Interestingly, during the period in which the diacylglycerol response was desensitized, a strong agonist-induced inhibition of Ca2+ entry and glutamate release was observed. This change in the presynaptic effects of 3,5-dihydroxyphenylglycine is reversible since 30 min after the first stimulation, the agonist-induced inhibition of release disappeared, whereas both the production of diacylglycerol and the facilitation of glutamate release were recovered. The tonic elevation of the extracellular glutamate concentration from basal levels (0.8 microM) up to 5 microM also produced the switch from facilitation to inhibition in the receptor response. The existence of this activity-dependent switch in the presynaptic control of glutamate release suggests that release facilitation is limited to conditions under which an appropriate clearance of synaptic glutamate exists, probably to prevent the neurotoxic accumulation of glutamate in the synapse.

Animals↗
PubMed1998

The metabotropic glutamate receptor 1 is not involved in the facilitation of glutamate release in cerebrocortical nerve terminals.

In this study we have addressed the identification of the metabotropic glutamate receptor (mGluR) involved in the facilitation of glutamate release in nerve terminals from the cerebral cortex. mGluR1 and 5 are coupled to phosphoinositide hydrolysis and the activation of these receptors with the specific agonist 3,5-dihydroxyphenylglycine (DHPG) enhances the release of glutamate. We have examined whether mGluR1 is responsible for this modulatory effect by preparing nerve terminals from mGluR 1 deficient mice. The Ca2+-dependent glutamate release evoked by a submaximal depolarization is enhanced by the agonist DHPG in nerve terminals from both wild and mutant mice. This result is consistent with the finding that the mGluR agonist also induces a similar increase in the levels of diacylglycerol (DAG) in the nerve terminals from wild and mutant mice. Moreover, the activity-dependent switch from facilitation to inhibition of release, observed when a second stimulation of the receptor is applied shortly after (5 min) the first pulse, was also observed in the mutant mice. These results indicate therefore, that the facilitation of glutamate release is unlikely to be due to the activation of mGluR1 but related to another phosphoinositide coupled mGluR.

Adenosine↗
PubMed1998

Effect of a platelet-activating factor (PAF) receptor antagonist on hyperacute xenograft rejection; evaluation in a pig kidney-human blood xenoperfusion model.

In pig to human discordant xenotransplantation, PAF may contribute to the pathogenesis of hyperacute xenograft rejection (HXR). We examined the release of PAF and the effect of a PAF receptor antagonist (BN 52021) on HXR in a pig kidney-human blood xenoperfusion model. Pig kidneys were perfused with porcine blood (AUTO group, n = 5), human blood (HETER group, n = 6) or human blood plus BN 52021 (BN group, n = 4), respectively. In contrast to HETER kidneys that never produced urine and were rejected in 15-30 min, the administration of BN 52021 induced a partial recovery of glomerular filtration rate and allowed kidneys to function until the end of the study. The release of PAF and soluble P-selectin, as well as endothelial P-selectin expression and tissue myeloperoxidase (MPO), were much higher in the HETER than in the AUTO group. HETER and BN kidneys displayed similar natural xenoantibody titres, CH50, PAF, soluble P-selectin as well as renal immunoglobulin (IgM, IgG, IgA) and complement (C3, C1q) deposition. However, HETER kidneys displayed a full histologic picture of HXR (mainly interstitial haemorrhage and vascular microthrombi) and BN kidneys had only endothelial cell swelling. Also, BN 52021 administration attenuated glomerular and vascular P-selectin expression and renal tissue MPO activity. We conclude that in the pig kidney-human blood xenoperfusion model, PAF is produced in higher amounts than in the pig kidney-pig blood autologous combination. The administration of BN 52021 exerts a protective effect by means of attenuating the acute inflammatory response and blocking vascular microthrombi formation.

Animals↗
PubMed1998

Prognosis of hepatocellular carcinoma in relation to treatment: a multivariate analysis of 178 patients from a single European institution.

BACKGROUND: Because the prognosis of patients with hepatocellular carcinoma is not fully understood, particularly regarding therapy, we have evaluated it in a series of patients with a homogeneous diagnostic and therapeutic work-up. METHODS: From 1985 to 1996, 42 variables were recorded prospectively in 178 constructive patients who had a diagnosis of hepatocellular carcinoma. Treatment consisted of liver transplantation ( n = 22), partial hepatectomy (n = 11), arterial, chemoembolization ( n = 52), systemic or regional chemotherapy (n = 51), and other therapies (n = 5); 37 patients received no specific therapy. Statistical analysis was performed according to a Cox model. RESULTS: There were no differences between the survival of patients receiving chemotherapy, other therapies, or no treatment (control group n = 93). survival rates a 1,3, and 5 years were 81%, 74%, and 74% for liver transplantation, 72%, 58%, and 58% for hepatectomy, 55%, 26%, and 13% for chemoembolization, and 13%, 3%, and 0% for the control group. Cirrhosis, systemic syndrome, bilobar involvement, Child's stage C disease, and treatment were independent predictors of survival. CONCLUSIONS: This series shows that certain easily accessible parameters may help establish individual prognosis and stratify patients in clinical trials and indicates that chemoembolization, partial resection, and liver transplantation can prolong life expectancy of patients with hepatocellular carcinoma.

Carcinoma, Hepatocellular↗
PubMed1997

Neutrophils accentuate renal cold ischemia-reperfusion injury. Dose-dependent protective effect of a platelet-activating factor receptor antagonist.

This study was undertaken to evaluate whether the renal damage induced by cold ischemia-reperfusion was worsened by neutrophils (PMN), and if blockade of platelet-activating factor (PAF) could effectively decrease this injury. After flushing with EuroCollins, 85 kidneys from Sprague-Dawley rats underwent either no cold ischemia or a 4-h cold ischemia, and then were reperfused for 75 min at 37 degrees C and 100 mm Hg in an isolated perfusion circuit. Reperfusion was performed with a Krebs-Henseleit solution containing 4.5% albumin, with and without human PMN (7.5 x 10(5) cells/ml) and with and without addition of a PAF receptor antagonist (BN 52021). Hemodynamic and functional parameters were continuously assessed during reperfusion. At end of the study, PAF production was evaluated. Presence of PMN during reperfusion of nonischemic kidneys produced no alteration of functional parameters or PAF production. After 4-h cold ischemia, the presence of PMN during reperfusion produced a significant worsening of plasma flow rate, glomerular filtration rate and sodium reabsorption in comparison with kidneys reperfused without PMN. Also, higher production of PAF was observed in the kidneys reperfused with PMN than in the kidneys reperfused without PMN. After 4-h cold ischemia, addition of BN 52021 during reperfusion in the presence of PMN significantly increased the plasma flow rate, glomerular filtration rate and sodium reabsorption in comparison with kidneys reperfused without this PAF antagonist. This effect was dose dependent. After 4-h cold ischemia, addition of BN 52021 during reperfusion in the absence of PMN produced no significant effect on functional parameters in comparison with kidneys reperfused without this PAF antagonist. These results indicate that PMN contribute to renal cold ischemia-reperfusion injury evaluated in the isolated perfused kidney. Treatment with a PAF receptor antagonist attenuated this injury in a dose-dependent manner, which suggests that it is mediated by PAF.

Animals↗