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Biomedical subjects

M Sánchez

Publications and source records attributed to M Sánchez.

At least 19 recordsLinked to original sources

Fresh human orthotopic ovarian cortex transplantation: long-term results.

BACKGROUND: Ovarian orthotopic transplantation in patients with premature ovarian failure is reported to result in full-term pregnancies. Ischaemia and freezing/thawing are potentially injurious for tissues. This study was designed to analyse the effect of ischaemia on long-term ovarian function in humans. METHODS: Prospective case-control study. Subjects were 12 premenopausal women undergoing hysterectomy and fresh orthotopic transplantation of the entire ovarian cortex plus a control group of five patients undergoing hysterectomy only. Follow-up lasted 2 years. Serum FSH and anti-Müllerian hormone (AMH) were recorded, and ovulatory cycles were determined by vaginal ultrasound and serum progesterone levels. RESULTS: Follow-up showed that ovulation was restored in 11 of the 12 patients who received grafts over the duration of the study (9.3 +/- 1.73 ovulations versus 12.0 +/- 0.86 in controls, NS), and 9 of 12 patients remained ovulatory after 2 years. We identified four patterns of FSH secretion during the study, 5 of 12 (41.7%) women having the same pattern as controls. There was a trend for serum AMH levels 7 days after surgery (0.16 +/- 0.02 microg/l) to be lower than pre-surgery levels (0.38 +/- 0.09 microg/l, P = 0.07) and higher in women whose FSH patterns suggested normal ovarian function, but the results did not reach significance. After transplantation, FSH correlated more closely (r = -0.639, P = 0.02) with normal ovarian function than AMH (r = 0.465, P = 0.12). CONCLUSIONS: Fresh orthotopic ovarian cortex transplantation is a viable procedure. It maintains normal ovarian function after 2 years in 75% of cases and preserves ovarian function against ischaemia in 41.7% of patients.

Adult↗

Pig liver gene therapy by noninvasive interventionist catheterism.

The efficacy of noninvasive interventionist catheterism in large animals as an alternative to the hydrodynamic procedure, described for small animals, is evaluated. Basically, gene transfer is performed by implantation and fixation of a balloon catheter within the suprahepatic vein of anesthetized pigs, through the femoral vein. The catheter tip is identified by fluoroscopy, injecting a contrast solution that marks large or small hepatic territories. Animals were injected with a 100 ml pTG7101 plasmid solution (40 microg/ml), which contains the human alpha-1 antitrypsin gene, perfused at a rate of 7.5 ml/s and efficacy and toxicity of the procedure were evaluated. The results show: (i) the highest efficacy in protein production is reached when perfusion is limited to small areas of the liver; (ii) no relevant hepatic toxicity was observed; (iii) gene transfer is mainly located in the areas around the central vein, as seen in the immunohistochemical studies; (iv) the electron microscopy studies indicate that the areas with good transfection efficacy show the presence of abundant endocytic vesicles that may even fuse among themselves. These data suggest that retrovenous injection by noninvasive interventionist catheterism could become an efficient procedure for hepatic gene transfer with potential clinical applications.

Animals↗

Is microbubble-enhanced ultrasonography sufficient for assessment of response to percutaneous treatment in patients with early hepatocellular carcinoma?

The objective of this study was to assess the efficacy of contrast-enhanced ultrasonography (CEUS) with SonoVue to evaluate the response to percutaneous treatment (ethanol injection/radiofrequency) of hepatocellular carcinoma in comparison with spiral computed tomography (CT) immediately and 1 month after treatment. Forty-one consecutive cirrhotic patients with early stage tumor (not suitable for resection) were included. Spiral CT and CEUS were performed in all patients before treatment, in the following 24 h, and 1 month later. The results of each examination were compared with the 1-month spiral CT, considered the gold standard technique. The 24-h CEUS and the 24-h spiral CT sensitivity to detect residual disease were 27% and 20%, respectively. The 24-h CEUS and the 24-h spiral CT positive predictive value of persistent vascularization detection were 75% and 66%, respectively. The 1-month CEUS detected partial responses in ten out of 11 cases (91% sensitivity, 97% specificity, 95% accuracy). Spiral CT and CEUS performed in the 24 h following treatment are slightly useful to evaluate therapeutic efficacy. The 1-month CEUS has a high diagnostic accuracy compared with spiral-CT in the usual assessment of percutaneous treatment response.

Administration, Cutaneous↗

Association between increased CCL2 (MCP-1) expression in lesions and persistence of disease activity in giant-cell arteritis.

OBJECTIVE: Patients with giant-cell arteritis (GCA) usually respond dramatically to corticosteroid treatment. However, recurrences are frequent and corticosteroid requirements are highly variable among patients. The aim of our study was to identify genes potentially involved in disease persistence. METHODS: Gene expression was explored with cDNA arrays in temporal artery biopsies from six GCA patients with relapsing disease and six patients who easily achieved sustained remission. Differentially expressed genes of interest were subsequently analysed by quantitative real-time polymerase chain reaction (PCR) and immunohistochemistry in temporal artery biopsies from 35 patients with biopsy-proven GCA and nine controls. RESULTS: CCL2 (MCP-1) was up-regulated in temporal artery samples from relapsing individuals. In the extended series of patients, CCL2 mRNA concentration in lesions was significantly higher than in controls (31 +/- 15.6 vs 0.44 +/- 0.10, P = 0.0001). In addition, CCL2 was more abundant in patients who experienced two or more relapses during the first year compared with those who endured sustained remission (127 +/- 82 vs 11 +/- 5.5, P = 0.0233) and correlated with the cumulated prednisolone dose (R = 0.533, P = 0.0024). CCL2 mRNA concentration correlated with IL-1beta (R = 0.45, P = 0.02), tumour necrosis factor-alpha (TNF-alpha) (R = 0.47, P = 0.013) and IL-6 (R = 0.52, P = 0.0053) mRNA. However, circulating CCL2 determined by ELISA was decreased in patients with strong systemic inflammatory response, suggesting that reduction in circulating CCL2 may reinforce the local gradient in lesions. CONCLUSION: Increased CCL2 (MCP-1) expression in lesions is associated with persistence of disease activity in GCA.

Anti-Inflammatory Agents↗

Efficacy of aminocaproic, tranexamic acids in the control of bleeding during total knee replacement: a randomized clinical trial.

BACKGROUND: Risks and costs of allogeneic blood transfusions mandate strategies to reduce blood loss in surgery. The objective of this study was to assess the efficacy of antifibrinolytic treatment in reducing perioperative blood loss during total knee replacement. METHODS: A double-blind, randomized and placebo-controlled clinical trial was carried out on 127 patients undergoing total knee replacement. Patients in the study group received tranexamic acid 10 mg kg(-1) i.v. just before the tourniquet was deflated and 3 h later, or epsilon-aminocaproic acid 100 mg kg(-1) before tourniquet deflation followed by continuous perfusion (1 g h(-1)) during 3 h. External perioperative blood loss was measured and total blood loss was calculated. The number of patients transfused and number of packed red cell (PRC) units transfused was recorded and possible postoperative thromboembolic complications were investigated. RESULTS: Total blood loss [mean (sd)] was 1099 ml (535) in the group that received antifibrinolytic agents and 1784 ml (660) in the control group (P<0.001). Five patients (7.5%) in the study group and 23 (38.3%) in the control group (P<0.001) received blood transfusions; the first group received a mean of 0.10 PRC unit per patient and the second, 0.58 (P<0.001). Mean reduction in haemoglobin levels (g dl(-1)) between preoperative and fifth day postoperative readings was 2.5 (0.9) in the study group and 3.4 (1.2) in the control group (P<0.001). Clinical assessment did not reveal any thromboembolic complications. CONCLUSIONS: Antifibrinolytic agents produce a significant decrease in blood loss in patients undergoing total knee replacement, reflected in a reduction in the number of blood transfusions required.

Aged↗

Lipid peroxidation in ischemia-reperfusion oxidative injury of the graft preserved in Celsior and University of Wisconsin solutions on a pig pancreas transplantation model.

BACKGROUND: Graft pancreatitis (GP) is one the main technical problems associated with pancreas transplant (PT). It occurs in 20% of patients representing a risk factor for thrombosis and cause of graft loss. GP is related to oxidative effects from oxygen-derived free radicals (OFR) in ischemia-reperfusion injury. We evaluated lipid peroxidation by the OFR in the PT of pig organs preserved with either Celsior or Wisconsin solutions. METHODS: In Landrace pigs we performed 24 pancreas allografts, which were preserved 18 or 24 hours: 12 with Celsior solution (CS) and 12 with Wisconsin solution (UW). No immunosuppression was administered. The oxidative effects were determined by quantification of malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) and of the carbonyl groups of proteins in our pancreatic tissue samples and measured at different times: (A) baseline in the donor, (B) after perfusion of the graft, (C) after the ischemia period, and (D) 30 minutes after ischemia-reperfusion of the graft. RESULTS: The MDA and 4-HDA values were similar in conditions A, B, and C, but showed an extraordinary increase after ischemia-reperfusion in D, among both the 18- or 24-hour preserved grafts and in the same proportion with CS and UW. The carbonyl groups of the proteins rose in conditions B and C (cold ischemia), but less so in state D (reperfusion). CONCLUSIONS: The oxidative injury of a pancreatic graft preserved for 18 or 24 hours occurs during reperfusion, with an extraordinary intensity, but similarly with CS and UW, an observation that may help to explain graft pancreatitis.

Adenosine↗

Intrathoracic fat in HIV-infected patients.

BACKGROUND: The impact of HIV infection or antiretroviral therapy on the intrathoracic fat compartment is unknown. METHODS: Consecutive clinically stable HIV-infected adult patients, irrespective of exposure to antiretroviral therapy, and non-HIV-infected healthy volunteers, both without clinical evidence of body fat changes consistent with lipodystrophy and adjusted for age, gender and body mass index, were recruited for this study. Thoracic and abdominal fat was assessed by computed tomography and compared between patients and controls. RESULTS: There were nine women (33%) and 18 men (67%) in each group. Nineteen patients (70%) had been taking antiretrovirals for a median of 8 months (interquartile range: 6-11). Among the HIV-infected patients, intrathoracic fat (median; interquartile range) did not differ significantly between treated (6.7 cm(2); 4.5-8.3 cm(2)) and untreated (6.9 cm(2); 5.7-10.9 cm(2)) individuals (P=0.288). However, intrathoracic fat content (median; interquartile range) was higher in HIV-infected patients (6.8 cm(2); 5.6-10.5 cm(2)) than in controls (5.6 cm(2); 3.9-6.7 cm(2)) (P=0.025). Intrathoracic fat was positively correlated with intra-abdominal fat both in patients (rho=0.6, P=0.002) and in controls (rho=0.7, P=0.004). CONCLUSION: In HIV-infected adults without clinical evidence of lipodystrophy, intrathoracic fat content was higher than in healthy persons and positively correlated with intra-abdominal fat content.

Abdomen↗

Identification and characterization of novel angiotensin-converting enzyme inhibitors obtained from goat milk.

The aim of the present study was to identify and characterize new inhibitory peptides of angiotensin I-converting enzyme (ACE) from goat milk and to analyze the effect of long-term intake of a goat milk hydrolysate-supplemented (GP-hyd) diet on the development of hypertension in spontaneously hypertensive rats (SHR). Three new inhibitory peptides for ACE (TGPIPN, SLPQ, and SQPK) were isolated. The inhibitory concentration 50% (IC50) values of individual peptides were 316, 330, and 354 micromol/L, respectively. Only TGPIPN was found to pass intact a monolayer of Caco-2 cells in small amounts. The SHR fed for 12 wk a diet (GP-hyd) enriched in a hydrolysate containing these peptides (estimated intake of TGPIPN was 230 mg/kg per d) showed lower (approximately 15 mmHg) systolic blood pressure than animals fed a control diet. The ACE activities in the aorta, left ventricle, and kidney were significantly decreased in the GP-hyd group compared with those of the control group and were similar to those found in SHR fed captopril (130 mg/kg per d). Impaired endothelium-dependent relaxation to acetylcholine by aortic rings from SHR was improved in those fed the GP-hyd diet. The left ventricle weight and kidney weight index were significantly reduced in the GP-hyd group and captopril groups. Moreover, long-term treatment of SHR with a diet enriched in goat milk hydrolysate, or captopril, attenuated the development of hypertension, cardiac and renal hypertrophy, and endothelial dysfunction. These effects might be related to the in vivo inhibitory effects of the hydrolysate on tissue ACE activity.

Angiotensin-Converting Enzyme Inhibitors↗

Simultaneous imbibition-heat convection process in a non-Darcian porous medium.

In the present work, the nonisothermal imbibition process in a porous medium was numerically analyzed using a non-Darcian model for the momentum equation and energy equations for the wetting and dry zones. In order to show the thermal character of the problem, we assume initially that the porous medium is found at a uniform temperature T0 and suddenly begins the imbibition process into the porous medium with a penetrating fluid at temperature T1. The physical influence of nondimensional parameters such as Peclet number, Pe, effective heat capacity number, beta(w), porous Reynolds number, Re(p), and the inertial coefficient of the porous medium, F, serve us to evaluate the position and velocity of the imbibition front as well as temperature profiles in both zones. In particular, for values of Re(p)F/beta(w)>>1, we recover a type of nonisothermal Washburn law. The numerical predictions show that the imbibition front and the temperature fields strongly depend on the above nondimensional parameters, revealing a clear deviation of the simple Washburn law.

Journal Article↗

The effect of flow path and mixing layer on phosphorus release: physical mechanisms and temperature effects.

Soil phosphorus (P) concentrations typically are greater in surface soils compared with subsurface soils. Surface soils have a greater chance to interact with runoff leading to P transport to streams. The thin surface layer where P concentrates is referred to as the mixing layer denoting where water and chemicals mix during transport. The objective of this study was to evaluate the effect of hydrologic flow paths on soluble reactive phosphorus (SRP) loss at two temperatures. Laboratory flumes were built to simulate infiltration, return flow, saturation excess, and interflow, and subsequent interaction with the mixing layer. The sandy loam soil in the flumes was kept at saturation throughout all experiments, so that biochemical effects were normalized. Flow through the flumes was maintained at 3.6 mm/h for 24 to 99 h (at 6 and 25 degrees C) with water entering and exiting the flumes at different ports (to simulate different flow paths) or as low intensity rainfall. Experiments were performed with and without an artificially created P-enriched surface layer (5 mm thick, total P increased from 1010 mg/kg in the original soil to 2310 mg/kg by addition of dissolved phosphate). Results indicated that (i) SRP release was greater in soil with a mixing layer than in soil without a mixing layer; (ii) SRP release was greater during experiments at 25 degrees C than at 6 degrees C; (iii) at 25 degrees C, SRP release was greatest when water traversed the mixing layer in the upward direction (i.e., in return flow), and by flow parallel to the mixing layer (i.e., surface runoff); and (iv) at 6 degrees C, SRP release in subsurface flow following rainfall was slightly greater than in return flow and infiltration. Our results confirmed the presence of a variable, temperature-dependent desorption process when runoff water interacted with the mixing layer. Our findings have important implications for how different water flow paths in and over the soil interact with P in the soil, and what the ultimate concentration will be in runoff and interflow.

Hydrogen-Ion Concentration↗

Effects of cinnarizine, a calcium antagonist that produces human parkinsonism, in parkin knock out mice.

Cinnarizine, a calcium antagonist that produces parkinsonism in humans, induces behavioural changes such as alopecia, buco-lingual dyskinesia and reduction of motor activity in female parkin knock out (PK-KO) mice but not in wild-type (WT) controls. PK-KO mice have high striatal dopamine levels and increased dopamine metabolism in spite of low reduced tyrosine hydroxylase protein. Cinnarizine, which blocks dopamine receptors and increases dopamine release, further increased dopamine metabolism. PK-KO mice increased GSH levels as a compensatory mechanism against enhanced free radical production related to acceleration of dopamine turnover. Neuronal markers, such as beta-tubulin slightly increased in PK-KO and furthermore with cinnarizine. Astroglial markers were decreased in PK-KO mice, and this effect was potentiated by cinnarizine, suggesting abnormal glia in these animals. Microglia was hyperactivated in PK-KO midbrain, suggesting inflammation in these animals. Proapoptotic proteins were increased by cinnarizine and, to a lesser extent, in PK-KO mice. Our data indicate that mutation of parkin is a risk factor for drug-induced parkinsonism.

Analysis of Variance↗

[Bilateral femoral cephalic osteonecrosis in a human immunodeficiency virus-infected child taking HAART].

Musculoskeletal complications are uncommon in HIV-infected patients. In adults, one manifestation is osteonecrosis which can be associated with risk factors such as alcohol consumption, smoking or use of corticosteroids. Such risk factors are rare in children. Over the last decade musculoskeletal complications have been observed in patients with advanced-stage disease or whose immune system has been reconstituted with highly active antiretroviral therapy (HAART). This complication has been reported in adults but to date not in children. We present the case of a 5-year-old child with AIDS (C stage 3) who developed osteonecrosis related to the advanced stage of the illness and to HAART. No risk factors were found.

Antiretroviral Therapy, Highly Active↗

Relative binding affinity of novel steroids to androgen receptors in hamster prostate.

The in vivo and in vitro antiandrogenic activity of four aromatic esters 10a-10d, one aliphatic ester 10e based on the pregna-4,16-diene-6, 20-dione structure and two aromatic 17c, 17d and two aliphatic valeroyloxy esters 17a, 17b based on the more saturated 4-pregnene-6,20-dione skeleton was examined. The biological activity of steroids 9, 10a-10e and 17a-17d, was determined using prostate glands from gonadectomized adult male golden hamsters. In the in vitro studies, the relative binding affinity of these steroids to cytoplasmic androgen receptor (AR) of hamster prostate was determined from, the corresponding IC50 values obtained from the competitive binding plots. The standards dihydrotestosterone (DHT) and cyproterone (CA) acetate used have displaced [3H]DHT from the AR with an IC50 value of 3.2 and 4.4 nM respectively. All steroidal compounds synthesized in this study showed a binding affinity for the androgen receptor, present in the cytosol from prostate hamster; compounds 10a-10c showed the highest affinities for this receptor. The in vivo experiments showed that all steroidal derivatives were subcutaneously active, since they decreased the weight of the prostate gland in gonadectomized hamsters treated with DHT, and are antagonists for the androgen receptor since they block the DHT-induced prostate weight gain. The derivatives having the more conjugated 4,16-pregnadiene-6, 20-dione system (10a-10c) exhibited a higher antiandrogenic activity than the corresponding steroids (17a-17d) based on the more saturated 4-pregnene-6,20-dione system.

Androgen Antagonists↗

The fertilizer value of pig slurry. I. Values depending on the type of operation.

151 samples of pig slurries were taken from 83 operations in the Castile-Leon region of Spain. Analysis of them enabled comparison of slurries coming from pig farming operations located in different Spanish and European regions. These operations were classified into three groups, namely maternity (64 samples), closed cycle (35 samples) and fattening (52 samples). For each sample 27 parameters were analysed. Data obtained from each kind of operation were compared. Finally, the fertilizer value of slurries was determined with regard to the relationship between their major elements, N/P2O5/K2O (1/0.6/0.4).

Agriculture↗

Quantitative pp65 antigenemia in the diagnosis of cytomegalovirus disease: prospective assessment in a cohort of solid organ transplant recipients.

OBJECTIVES: To assess the accuracy of quantitative pp65 antigenemia (pp65Ag) in the diagnosis of CMV disease, in a cohort of solid-organ transplant recipients. METHODS: Prospective observational study during the first 6 months following transplantation, with determination of pp65Ag at weeks 2, 4, 6, 8, 10, 11, 12, 14 and 16. Sensitivity (S), specificity (E), positive and negative predictive values (PPV, NPV), and the optimal cut-off point for diagnosing CMV disease, were determined. RESULTS: The cohort consisted of 35 liver, 26 renal and 12 heart graft recipients. Thirteen (17.2%) were seronegative and received a seropositive graft. Of 583 blood samples, pp65Ag was positive in 109 (18.7%) from 37 patients (51%). Twenty-two patients developed CMV disease (0.3 episodes/patient); gastrointestinal disease was the most frequent (15 episodes), followed by viral syndrome (3 episodes). Patients with positive pp65Ag had a relative risk for CMV disease of 6.19 [IC95%=1.99-19.04], (P=.0001). Diagnostic values of pp65Ag were: S=86%, E=65%, PPV=51%, NPV=92%. The cut-off of > or =10 infected cells/10(5), at weeks 2, 4, 6 and 8 obtained the best PPV (0, 67, 91 and 54%), and NPV (47, 52, 67 and 50%). CONCLUSIONS: In the studied population, the presence of positive pp65Ag was associated with a high risk of developing CMV disease, and the most useful cut-off point for the diagnosis was > or =10 infected cells/10(5).

Adult↗

Silymarin induces recovery of pancreatic function after alloxan damage in rats.

Alloxan has been widely used to produce experimental diabetes mellitus syndrome. This compound causes necrosis of pancreatic beta-cells and, as is well known, induces oxidant free radicals which play a relevant role in the etiology and pathogenesis of both experimental and human diabetes mellitus. Previously we have reported hypoglycemic and antilipoperoxidative actions of silymarin in serum and pancreatic tissue respectively. The aim of this study was to test whether silymarin could reduce the hyperglycemia and revert the pancreatic damage in alloxan treated rats, tested with silymarin in two protocols: using both compounds simultaneously for four or eight doses, or using the compound 20 days after alloxan administration for 9 weeks. Serum glucose and insulin were determined, and pancreatic fragments were used for histology and insulin immunohistochemistry. Pancreatic islets were isolated to assess insulin and Pdx1 mRNA expression by RT-PCR. Our results showed that 72 hours after alloxan administration, serum glucose increased and serum insulin decreased significantly, whereas pancreatic tissue presented morphological abnormalities such as islet shrinkage, necrotic areas, loss of cell organization, widespread lipoid deposits throughout the exocrine tissue, and loss of beta cells, but insulin and glucagon immunoreactivity was scattered if any. In contrast the pancreatic tissue and both insulin and glucose serum levels of rats treated with silymarin were similar to those of control animals. In addition, insulin and glucagon immunoreactive cells patterns in Langerhans islets were also normal, and normal insulin and Pdx1 mRNA expression patterns were detected during pancreatic recovery in Langerhans islets. The overall results suggest that silymarin induces pancreatic function recovery demonstrated by insulin and glucagon expression protein and normoglycemia after alloxan pancreatic damage in rats.

Animals↗

Enriched protein diet-modified ghrelin expression and secretion in rats.

Gastrointestinal (GI) integrity and function are regulated by nutrition and growth factors. The discovery of ghrelin, a natural growth hormone (GH) secretagogue produced by the gastrointestinal (GI) tract, is a potential link between diet and growth signals. The aim of this study was to evaluate macronutrient effect on ghrelin expression and secretion in addition to some possible function in intestinal trophic status. Wistar rats were fed a high-carbohydrate, high-protein (HP), high-fat or standard (St) diet. Animals received the same daily food volume and caloric intake. After 7 days, animals were fasted for 24 h and blood and tissue samples were obtained just before feeding or at 2 or 6 h after feeding. Fasting high-protein-fed rats had higher ghrelin plasma levels than with rats fed the high-carbohydrate, high-fat or standard diets. Two-hours after refeeding, ghrelin plasma levels had decreased in all groups with a slight recovery at 6 h after refeeding, except in the high-protein group. Ghrelin plasma levels in rats fed with the high-protein diet correlated negatively with their GH and insulin-like growth factor 1 (IGF-1) plasma concentrations which were also the lowest among the study groups. In conclusion, ghrelin secretion was nutritionally manipulated because a protein-enriched diet increased its levels.

Animals↗