[Ferritin, diabetes and hepatitis C virus].
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Biomedical subjects
Publications and source records attributed to C Hernández.
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1. The gastric mucosa of portal hypertensive rats exhibits important microvascular changes and a nitric oxide (NO)-dependent hyperemia. This study analyses whether portal hypertensive mucosa exhibits changes in its ability to withstand aggression. 2. Portal hypertension was induced by partial portal vein ligation (PPVL) or common bile duct ligation (CBDL) and gastric damage was induced by oral administration of ethanol or aspirin. Experiments were performed in conscious or anaesthetized rats and some animals were pre-treated with the NO-synthesis inhibitor L-NAME. 3. Conscious PPVL or CBDL rats showed an increased resistance to the damaging effects of ethanol. Oral administration of aspirin produced less gastric damage in PPVL conscious rats than in the control group. 4. The protective effects of portal hypertension were maintained in animals anaesthetized with ketamine and absent when pentobarbital was employed. 5. Pre-treatment with L-NAME restored the damaging effects of ethanol and aspirin in PPVL rats without modifying the level of damage in control animals. 6. Gastric bleeding induced by oral aspirin, as measured by the luminal release of (51)Cr-labelled erythrocytes, was significantly greater in PPVL rats than in control animals. 7. Semi-quantitative analysis by RT--PCR of the mRNA for endothelial NO-synthase (eNOS), neuronal NOS (nNOS) and inducible NOS (iNOS) levels showed that the expression of iNOS was slightly increased in both the gastric mucosa and smooth muscle of PPVL rats. No changes were observed in eNOS and nNOS expression. 8. Conscious portal hypertensive rats exhibit an enhanced resistance to acute gastric damage which is absent under the influence of some types of anaesthesia and seems related to an increased synthesis of nitric oxide. However, mucosal lesions in these animals show an augmented bleeding per area of injury.
An increased prevalence of hepatitis C virus (HCV) infection in patients with diabetes and a higher prevalence of diabetes in HCV-infected patients have been reported. However, the relationship between these two conditions remains controversial. In addition, although the effect of interferon treatment on thyroid autoimmunity has been extensively reported, its influence on beta-cell autoantibodies has not been investigated. The aims of the study were (1) to evaluate whether autoimmune beta-cell damage could be involved in the development of diabetes mellitus in HCV-infected patients and (2) to determine whether interferon treatment influences the appearance of beta-cell and thyroid autoantibodies. The prevalence of islet cell autoantibodies (glutamic acid decarboxylase antibodies [GADAs], tyrosine phosphatase antibodies [IA-2s], islet cell antibodies [ICAs]) was assessed in 303 non-selected HCV-infected patients (277 non-diabetic and 26 type 2 diabetic patients) and in 273 sex- and age-matched control subjects. ICAs and thyroid autoantibodies were also determined before and 6 and 12 months after treatment with interferon for 24 weeks in a subgroup of 46 HCV-infected patients. GADAs were detected in 4 of 277 (1.4%) HCV-infected non-diabetic patients, 1 of 273 (0.3%) control subjects, and 0 of 26 (0%) HCV-infected patients with diabetes. Anti-IA2s and ICAs were negative in all subjects. Both GADAs and anti-IA2s were negative in all HCV-infected patients treated with interferon. After therapy, only thyroid antibodies became positive in 5 of 46 (10.9%) treated patients, disappearing in all but 1 of these at the 12-month follow-up. Our results suggest that beta-cell autoimmunity is not associated with HCV infection, thus making it unlikely that the increased diabetes mellitus prevalence among HCV-infected patients could be mediated by autoimmune mechanisms. In addition, interferon treatment induces a transient increase in thyroid autoantibodies but does not influence the appearance of beta-cell autoantibodies.
OBJECTIVE: To evaluate the relationship between plasma lipid profiles and lipoprotein(a) [Lp(a)] concentrations in diabetic patients, taking into account the Lp(a) phenotype. RESEARCH DESIGN AND METHODS: We included 191 consecutive diabetic outpatients (69 type 1 and 122 type 2 diabetic patients) in a cross-sectional study Serum Lp(a) was determined by enzyme-linked immunosorbent assay, and Lp(a) phenotypes were assessed by SDS-PAGE followed by immunoblotting. The statistical methods included a stepwise multiple regression analysis using the Lp(a) serum concentration as the dependent variable. The lipid profile consisted of total cholesterol, HDL cholesterol, LDL cholesterol, corrected LDL cholesterol, triglycerides, and apolipoproteins AI and B. RESULTS: In the multiple regression analysis, LDL cholesterol (positively) and triglycerides (negatively) were independently related to the Lp(a) concentration, and they explained the 6.6 and 7.8% of the Lp(a) variation, respectively. After correcting LDL cholesterol, the two variables explained 3.8 and 6.4% of the Lp(a) variation, respectively. In addition, we observed that serum Lp(a) concentrations were significantly lower in patients with type IV hyperlipidemia (mean 1.0 mg/dl [range 0.5-17], n = 16) than in normolipidemic patients (6.5 mg/dl [0.5-33.5], n = 117) and in type II hyperlipidemic patients (IIa 15.5 mg/dl [3.5-75], n = 13; IIb 9 mg/dl [1-80], n = 45); P < 0.001 by analysis of variance. CONCLUSIONS: Lp(a) concentrations were directly correlated with LDL cholesterol and negatively correlated with triglyceride levels in diabetic patients. Therefore, our results suggest that the treatment of diabetic dyslipemia may indirectly affect Lp(a) concentrations.
D-003 is a mixture of higher aliphatic primary acids purified from sugar cane wax (Saccharum officinarum) with cholesterol-lowering and antiplatelet effects experimentally proven. The present work reports the results of two studies investigating the acute and subchronic oral toxicity of D-003 in rats. Oral acute toxicity of D-003 (2000 mg/kg) was investigated according to the Acute Toxic Class (ATC) method (an alternative for the classical LD(50) test), which was performed in Wistar rats. The results obtained in this study defined D-003 oral acute toxicity as unclassified. In the subchronic study, rats of both sexes were orally treated with D-003 at 50, 200 and 1250 mg/kg for 90 days. At this time, animals were sacrificed. No evidence of treatment-related toxicity was detected during the study. Thus, data analysis of body weight gain, food consumption, clinical observations, blood biochemical, haematology, organ weight ratios and histopathological findings did not show significant differences between control and treated groups. It is concluded that D-003 orally administered to rats was safe and that no drug-related toxicity was detected even at the highest doses investigated in both acute (2000 mg/kg) and subchronic (1250 mg/kg) studies.
OBJECTIVES: We sought to assess the fate of stent (ST)-related side branches (SB) after coronary intervention in patients with in-ST restenosis. BACKGROUND: In-ST restenosis constitutes a therapeutic challenge. Although the fate of lesion-related SB after conventional angioplasty or initial coronary stenting is well established, the outcome of ST-related SB in patients with in-ST restenosis undergoing repeat intervention is unknown. METHODS: One hundred consecutive patients (age 61 +/- 11 years, 22 women) undergoing repeat intervention for in-ST restenosis (101 ST) were prospectively studied. Two hundred and twenty-six SB spanned by the ST were identified. The SB size, type, ostium involvement, location within the ST and take-off angle were evaluated. The SB TIMI (Thrombolysis in Myocardial Infarction trial) flow grade was studied in detail before, during, immediately after the procedure, and at late angiography. RESULTS: Occlusion (TIMI flow grade = 0) was produced in 24 (10%) SB, whereas some degree of flow deterioration (> or = 1 TIMI flow grade) was observed in 57 SB (25%). The SB occlusion was associated with non-Q wave myocardial infarction in two patients (both had large and diseased SB). Side-branch occlusion at the time of initial stenting (RR [relative risk] 11.1, 95% CI [confidence interval] 3.5-35.5, p < 0.001), diabetes (RR 3.5, 95% CI 1.1-10.5, p = 0.02), SB ostium involvement (RR 5.0, 95% CI 1.4-17.2, p = 0.004), baseline SB TIMI flow grade <3 (RR 5.5, 95% CI 1.7-18.1, p = 0.005), and restenosis length (RR 1.05 95% CI 1.01-1.11, p = 0.03) were identified as independent predictors of SB occlusion. Late angiography in 19 initially occluded SB revealed that 17 (89%) were patent again. The long-term clinical event-free survival (81% vs. 82% at two years) in patients with and without initial SB occlusion was similar. CONCLUSIONS: Occlusion or flow deterioration of SB spanned by the ST is relatively common during repeat intervention for in-ST restenosis. Several factors (mainly anatomic features) are useful predictors of this event. However, most SB occlusions are clinically silent and frequently reappear at follow-up.
BACKGROUND: To study distinctive clinical features of pheochromocytoma in the setting of multiple endocrine neoplasia type 2A (MEN 2A) in comparison with sporadic pheochromocytoma. PATIENTS AND METHOD: All patients diagnosed of sporadic pheochromocytoma (n = 29) and in the setting of MEN 2A (n = 16) between 1976 and 1998 in a tertiary hospital were included in the study. The following variables were compared: age at diagnosis, symptoms, presence and characteristics of hypertension, size of the tumor, localization and malignancy. The accuracy of diagnostic tests was also evaluated. RESULTS: The pheochromocytoma associated to MEN 2A had a higher prevalence in our study (35.5%) and the diagnosis was performed earlier than for sporadic pheochromocytoma (29.1 [7.8] vs. 47,5 [10. 9] years; p < 0.001). Other distinctive features in comparison with sporadic pheochromocytoma were: bilaterality (81.25 vs. 3.44%; p < 0. 001), absence of symptoms (44 vs 11%; p < 0.05) and paroxysmal hypertension. Concerning the diagnostic tests, it must be noted the low sensitivity (60%) of vanillylmandelic acid in MEN 2A. CONCLUSIONS: The pheochromocytoma in the setting of MEN 2A is diagnosed at younger age and frequently asymptomatic and bilateral. In view of the high prevalence of MEN 2A in our country, a genetic analysis should be performed in all patients with pheochromocytoma, especially when it is bilateral.
It has been demonstrated in vitro that lipoprotein(a) [Lp(a)] increases the endothelial synthesis of plasminogen activator inhibitor 1 (PAI-1). However, this effect in vivo is controversial, and the possible relationship between PAI-1 and Lp(a) phenotypes has not been evaluated. The aim of the study was to determine the influence of Lp(a) and its phenotypes on PAI-1 serum concentrations in diabetic patients. For this purpose we include 75 Caucasian diabetic patients (34 consecutive type I and 41 consecutive type II) without late diabetic complications. Lp(a) and PAI-1 were assessed by ELISA. Lp(a) phenotypes were determined by SDS-PAGE followed by immunoblotting, and grouped according to size in small (F,B,S1,S2), big (S3,S4), and null. A linear correlation between Lp(a) and PAI-1 was not observed either as a whole or when type I and type II diabetic patients were analyzed separately. However, significant differences were detected in PAI-1 levels when Lp(a) phenotypes were considered (small: 42.1+/-31.8 ng/mL; big: 37.2+/-26.1 ng/mL; null: 14.4+/-14.4; p< 0.05). The significant differences were due to the low PAI-1 concentrations observed in patients with null phenotype. Our results suggest that fibrinolytic activity might be preserved in diabetic patients with null Lp(a) phenotype. Furthermore, it could be speculated that diabetic patients with null phenotype should be considered at low risk to develop cardiovascular disease.
BACKGROUND: To investigate whether the high prevalence of diabetes observed in patients infected by the hepatitis C virus (HCV) is associated to iron stores. PATIENTS AND METHODS: Serum ferritin levels were determined in 123 patients infected by HCV (55 diabetic and 68 non-diabetic). RESULTS: Serum ferritin concentrations were higher in diabetic than in non-diabetic patients (205 ng/ml [14-861] vs. 58 ng/ml [15-494]; p < 0.0001). CONCLUSIONS: Serum ferritin levels are related with the presence of diabetes in patients infected by HCV.
BACKGROUND: There is no consensus about the best follow-up protocol in differentiated thyroid carcinoma (DTC). The aim of this study is to evaluate the usefulness and prognostic value of serum thyroglobulin (Tg) and the iodide-131 whole body scan (WBS) in DTC recurrences as a whole and according to the type of recurrence (local recurrence or distant metastases). PATIENTS AND METHODS: Thirty-four patients with recurrent DTC recruited in our institution over 15 years, with a minimum 5 years of follow-up and without either distant metastases at time of diagnosis nor detectable anti-Tg antibodies were included in the study. All patients were submitted to total or near-total thyroidectomy and 131INa ablation of postsurgical thyroid remnants. The follow-up included Tg measurement and WBS performed in hypothyroid state. RESULTS: Serum Tg was increased in the 67.4% of the patients and the WBS was positive in the 82.3%. In the isolated local recurrences the sensitivity of WBS was higher than Tg measurement (93.7 vs 43.7%; p < 0.05), but patients with positive Tg had a worse prognostic. By contrast, in patients with distant metastases the sensitivity of Tg was higher than WBS (83.3 vs 58.3%; p = NS). In 14 patients (41.2%) the results of WBS and Tg were in disagreement. In these cases a worse prognosis was observed when Tg was positive and WBS negative. CONCLUSIONS: The sensitivity of Tg and WBS is different depending on the type of recurrence. Therefore, both tests complement each other and it is not recommended to omit one of them in the follow-up of DTC.
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We present a case in which, after performing an optimal angioplasty after an acute myocardial infarction with intracoronary thrombus, normal coronary flow was not achieved. After aspirating through the guiding catheter we obtained a large thrombus that the histopathologic study confirmed as a recent thrombus and, subsequently, normal flow was reestablished. The procedure was completed with a successful intracoronary stent implantation, with an uneventful clinical course. The therapeutic and diagnostic implications of this case are discussed.
UNLABELLED: Experimental studies suggest that leptin may be an important metabolic signal for energy regulation. AIM: To assess whether surgical stress produces changes in serum leptin concentration and to investigate and compare the effect of total parenteral nutrition and hypocaloric parenteral nutrition on serum leptin levels. PATIENTS AND METHODS: Twenty-two surgical patients (11 male and 11 female) in need of parenteral nutrition were recruited. Parenteral nutrition was always initiated 24 h after surgical procedure. Group I (n=15) received total parenteral nutrition, while Group II (n=7) were treated with hypocaloric parenteral nutrition. Serum leptin concentration was determined before surgical procedure (day -1), after surgery and before parenteral nutrition was started (day +1), and after 5 days of treatment with parenteral nutrition (day +6). RESULTS: A tendency to increase serum leptin levels was observed after surgical procedure (6.0+/-1.9 vs 9.9+/-2.7 ng/ml;P= 0.07). After starting parenteral nutrition no significant changes on serum leptin concentrations were found in both groups, but a trend to raise serum leptin was observed in Group I (6.2+/-1.7 vs 8.3+/-2.7 ng/ml) whereas a trend to decrease serum leptin was detected in Group II (4.6+/-2.5 vs 1.6+/-0.5 ng/ml). On day +6 an increase of serum leptin and insulin levels was observed in Group I in comparison with Group II (8.3+/-2.7 vs 1.6+/-0.5 ng/ml;P<< 0.05 and 58+/-41 vs 12+/-15 microU/l;P<< 0.05 respectively). Finally, a positive correlation at day +6 between insulin and serum leptin levels was observed (r= 0.66;P<< 0.01). CONCLUSIONS: a) Surgical stress is associated to an increase of serum leptin concentrations; b) Total and hypocaloric parenteral nutrition produces quite different effects on serum leptin levels that could be related to distinct insulin response.
Carnation small viroid-like RNA (CarSV RNA) and its homologous DNA are the two forms of a unique plant retroviroid-like system. CarSV RNA is a 275-nucleotide noninfectious viroid-like RNA, present in certain carnation plants, which can adopt hammerhead structures in both polarity strands and self-cleave accordingly. CarSV DNA is organized as a series of head-to-tail multimers forming part of extrachromosomal elements in which CarSV DNA sequences are fused to sequences of carnation etched ring virus (CERV), a plant pararetrovirus. Analysis of more than 30 CarSV-CERV DNA junctions showed that distinct regions of the viral genome seem able to interact with CarSV DNA. All these junctions were short nucleotide stretches common to both CarSV and CERV DNAs. This suggests a polymerase-driven mechanism for their origin involving an enzyme with low processivity, most likely the viral reverse transcriptase. This view was further supported by the observation that most of CarSV sequences forming part of the junctions correspond either to strong secondary structure motifs in the conformation proposed for CarSV RNA or to its self-cleavage sites, which may have facilitated polymerase jumping. Accompanying the most-abundant CarSV RNA, a series of CarSV RNAs with sequence deletions were previously characterized. Here we have identified some of their corresponding DNA forms, together with other CarSV DNA forms with deletions not found in any CarSV RNA species identified so far. Some of these CarSV DNA forms have also been detected fused to CERV sequences. The existence of these shortened CarSV DNA versions may provide a continuous input of their corresponding transcripts and explain the persistence of CarSV RNAs with defective hammerhead structures for which an RNA-RNA model of amplification seems unlikely.
BACKGROUND: Hepatocyte growth factor (HGF) is an endothelium specific growth factor that has been implicated in angiogenesis, a crucial event for the development of proliferative diabetic retinopathy (PDR). The aim of the study is to determine the intravitreous concentrations of HGF in diabetic patients with PDR, and to investigate whether its serum levels could contribute to its intravitreous concentration. METHODS: 17 diabetic patients and seven non-diabetic patients in whom a vitrectomy was performed were studied. Both groups were matched by serum levels of HGF. Venous blood and vitreous samples were collected simultaneously at the time of vitreoretinal surgery. Vitreous and serum HGF were determined by ELISA. RESULTS: Intravitreous concentrations of HGF (median and range) were higher in diabetic patients (17.04 ng/ml (9.98-80)) in comparison with non-diabetic patients (5.88 ng/ml (2.57-14.20); p=0. 003). Intravitreous HGF concentrations were strikingly higher than serum HGF concentrations both in diabetic patients (17.04 ng/ml (9. 98-80) v 0.66 ng/ml (0.26-1.26); p<0.001) and in the control group (5.88 ng/ml (2.57-14.20) v 0.68 ng/ml (0.49-0.96); p=0.003). No correlation was found between serum and vitreous levels of HGF in both groups (diabetic patients, r= -0.31; p=0.5 and control subjects r= -0.15; p=0.5). CONCLUSION: The high vitreous levels of HGF observed in diabetic patients with PDR cannot be attributed to serum diffusion across the blood-retinal barrier. Therefore, intraocular synthesis appears to be the main contributing factor for the high vitreous HGF concentrations in diabetic patients, a cytokine that seems to be directly involved in the pathogenesis of PDR.
BACKGROUND/AIM: The possible association between lipoprotein(a) [Lp(a)] and albumin excretion rate (AER) is a topic that has generated conflicting views. The aim of this study was to determine the relationship between serum Lp(a) concentrations and AER in diabetic patients, taking into account Lp(a) phenotypes in a multivariate analysis. METHODS: For this purpose 191 consecutive diabetic patients (69 type 1 and 122 type 2) were included in the study. Lp(a) was determined by ELISA and its phenotypes by SDS-PAGE followed by immunoblotting. Lp(a) phenotypes were grouped by size in small (F, B, S1, S2), big (S3, S4) and null. RESULTS: Diabetic patients with an AER >20 microg/min presented higher Lp(a) concentrations than patients with an AER <20 microg/min: median 19 mg/dl versus 5 mg/dl (p < 0.0001). The differences remained at a significant level when the type of diabetes was considered. A linear correlation was observed between Lp(a) concentration and AER (type 1: r = 0.32, p = 0.01; type 2: r = 0.25, p < 0.05). The AER was independently correlated with Lp(a) concentrations in a multiple regression analysis (p < 0.01), and Lp(a) was independently associated with the presence of diabetic nephropathy in the logistic regression analysis. The overall frequency distribution of Lp(a) phenotypes differed significantly between patients with or without microalbuminuria (p < 0.05). In addition, the AER (microg/min) was different among the Lp(a) phenotypes: small 55 +/- 122 (median 4.9), big 58 +/- 123 (median 5.7) and null 3 +/- 2 (median 2.3); p = 0.01. The significant difference mainly resulted from low AER (<10 microg/min) detected in all patients with the null phenotype. CONCLUSIONS: In diabetic patients the serum Lp(a) concentration is associated with AER. Thus, the elevated cardiovascular risk observed in diabetic patients with a high AER could be related to the Lp(a) concentration. Finally, patients with the null Lp(a) phenotype can be considered as a group at low risk of the development of diabetic nephropathy.