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Biomedical subjects

M Gonzalez

Publications and source records attributed to M Gonzalez.

At least 55 records · Page 3Linked to original sources

Intestinal anti-inflammatory activity of morin on chronic experimental colitis in the rat.

BACKGROUND: Morin, a bioflavonoid with antioxidant properties, shows intestinal anti-inflammatory activity in the acute phase of the trinitrobenzenesulphonic acid model of rat colitis. AIM: To assess the anti-inflammatory activity of morin in the chronic stages of trinitrobenzenesulphonic acid-induced rat colitis. METHODS: Rats were rendered colitic by a single colonic instillation of 30 mg of the hapten trinitrobenzenesulphonic acid dissolved in 0.25 mL of 50% ethanol. A group of colitic animals was given morin orally at doses of 25 mg/kg daily. Animals were sacrificed every week for 4 weeks. Colonic damage was evaluated macroscopically and microscopically. Different biochemical markers of colonic inflammation were also assayed, including myeloperoxidase activity, leukotriene B4 and interleukin-1beta synthesis, glutathione and malonyldialdehyde levels and nitric oxide synthase activity. RESULTS: The administration of morin facilitated tissue recovery during the 4 weeks following colonic insult with trinitrobenzenesulphonic acid, as demonstrated macroscopically and microscopically, as well as biochemically by a reduction in myeloperoxidase activity. The intestinal anti-inflammatory effect of morin was accompanied by a significant reduction in colonic leukotriene B4 and interleukin-1beta levels, improvement in colonic oxidative stress and inhibition of colonic nitric oxide synthase activity. CONCLUSIONS: Morin exerts a beneficial anti-inflammatory effect in the chronic phase of trinitrobenzenesulphonic acid-induced rat colitis through the down-regulation of some of the mediators involved in the intestinal inflammatory response, including free radicals, cytokines, leukotriene B4 and nitric oxide.

Administration, Oral↗

The effect of hair loss on quality of life.

BACKGROUND: The aim of this study was to quantify the effect of hair loss on quality of life. Patients were recruited from an alopecia support group, and were assessed using the Dermatology Life Quality Index (DLQI) and an adapted version of the DLQI. Financial utility questions, an abbreviated version of the Center for Epidemiologic Studies Depression Scale and open-ended questions were also used. OBSERVATIONS: Seventy (90% response rate) questionnaires were returned. DLQI scores in responders with hair loss (mean score = 8.3, SD = 5.6, range 0-23, n = 70) were similar to those recorded in severe psoriasis. The hair loss continued to have a significant impact on life quality well after the initial event (median duration of hair loss = 138 months +/- 114; range 7-588, n = 70). Forty per cent of patients also felt dissatisfied with the way in which their doctor dealt with them. CONCLUSIONS: This study specifically identifies the feelings of loss of self-confidence, low self-esteem and heightened self-consciousness in people affected by hair loss.

Adult↗

Positional changes and stability of bone segments during simultaneous bilateral mandibular lengthening and widening by distraction.

The purpose of this study was to analyse the skeletal changes and stability of the distracted segments during and after simultaneous widening and bilateral lengthening of the mandible in baboons with a miniaturized intraoral bone-borne osteodistractor. Distraction appliances were activated 5 days after vertical posterior body and midsymphyseal osteotomies at a rate of 0.9 mm/day for 10 days. The appliances were then stabilized for a period of 8 weeks, after which the animals were killed. The distraction gaps and gingival tissues were studied clinically and on standardized radiographs. The proportional movement of the distracted segments that we found supports the clinical use of the miniaturized intraoral bone-borne distraction appliance to widen and lengthen the mandible selectively. It also supports the concept of positioning the mandibular osteodistractors parallel to the common vector of distraction, which should parallel the corrected maxillary occlusal plane.

Animals↗

Variability in the levels of PML-RAR alpha fusion transcripts detected by the laboratories participating in an external quality control program using several reverse transcription polymerase chain reaction protocols.

BACKGROUND AND OBJECTIVES: The detection of PML-RAR by reverse transcription (RT) polymerase chain reaction (PCR) in acute promyelocytic leukemia (APL) patients who are in hematologic remission influences therapeutic decision making in several trials. In the light of this, the Spanish group has recently designed an external quality assessment program (EQAP) of RT-PCR detection of PML-RAR, which includes a study of sensitivity of the participating laboratories. DESIGN AND METHODS: Eighteen laboratories were involved in the program. Ten laboratories followed the method of Biondi et al., 5 employed that of Borrow et al. and the 3 remaining used other protocols. The sensitivity was studied in five rounds of quality control. The first two shipments consisted of dilutions of NB4 RNA into non-APL RNA. The third round consisted of serial dilutions of the NB4 cell line into HL60 cells. The fourth and five rounds consisted of plasmid dilutions containing the bcr1 and bcr3 PML-RAR isoforms. RESULTS: The results showed that the distinct methods allow detection of the PML-RAR hybrid up to a dilution of 10(-4), and exceptionally, up to 10(-5). The laboratories following the method of Biondi et al. usually detected the 10(-3) dilution and less frequently the 10(-4) one, whereas those using other methods usually detected PML-RAR transcript in the 10(-4) dilution, and less commonly in the 10(-5) dilution. However, each of the PCR methods used by EQAP participating laboratories successfully detected at least 50 copies of PML-RAR alpha fusion transcript in plasmid dilution controls. INTERPRETATION AND CONCLUSIONS: The results point to heterogeneous sensitivity amongst participating laboratories. This may reflect differences in methodology, although variations in sample quality may also account for discrepant findings.

Humans↗

Stabilization of homogeneous preparations of pregnancy zone protein lyophilized in the presence of saccharose. Structural and functional studies.

Human pregnancy zone protein (PZP) is a macromolecule of 360 kDa, organized as a disulfide-linked homodimer of two 180 kDa subunits, with an amino acid sequence and structure remarkably similar to that of human alpha2-Macroglobulin. Homogeneous PZP samples undergo fast aging forming oligomeric aggregates of high molecular weight. This aged PZP loses its ability to interact with proteinases and consequently, non-recognition of receptors occurs. In the present work, we assessed the effect of saccharose on the stability of native PZP on lyophilized samples kept for a long period of time. Herein, we demonstrate that the addition of 0.25 M saccharose to homogeneous PZP and further lyophilization is enough to prevent aging and preserve functional activity for more than 1 year. Hence, high quality samples, in terms of purity, stability and functional activity will allow to develop biochemical studies in order to know the PZP role in physiological and pathological states where the protein levels are increased, such as pregnancy and tumoral disorders.

Calorimetry, Differential Scanning↗

Subunit-specific degradation of the UmuD/D' heterodimer by the ClpXP protease: the role of trans recognition in UmuD' stability.

The Escherichia coli UmuD' protein is a subunit of the recently described error-prone DNA polymerase, pol V. UmuD' is initially synthesized as an unstable and mutagenically inactive pro-protein, UmuD. Upon processing, UmuD' assumes a relatively stable conformation and becomes mutagenically active. While UmuD and UmuD' by themselves exist in vivo as homodimers, when together they preferentially interact to form heterodimers. Quite strikingly, it is in this context that UmuD' becomes susceptible to ClpXP-mediated proteolysis. Here we report a novel targeting mechanism designed for degrading the mutagenically active UmuD' subunit of the UmuD/D' heterodimer complex, while leaving the UmuD protein intact. Surprisingly, a signal that is essential and sufficient for targeting UmuD' for degradation was found to reside on UmuD not UmuD'. UmuD was also shown to be capable of channeling an excess of UmuD' to ClpXP for degradation, thereby providing a mechanism whereby cells can limit error-prone DNA replication.

Adenosine Triphosphatases↗

Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and GIMEMA cooperative groups.

Preliminary independent reports of the Italian GIMEMA and the Spanish PETHEMA trials for newly diagnosed acute promyelocytic leukemia (APL) indicated a similarly high antileukemic efficacy in terms of complete remission and disease-free survival rates. To better investigate these studies and the prognostic factors influencing relapse risk, this study analyzed the updated results of 217 patients with PML/RAR alpha-positive APL enrolled in GIMEMA (n = 108) and PETHEMA (n = 109). All patients received identical induction (AIDA schedule) and maintenance. For consolidation, GIMEMA patients received 3 courses including idarubicin/cytarabine, mitoxantrone/etoposide, and idarubicin/cytarabine/thioguanine, whereas PETHEMA patients received the same drugs and dose schedule of idarubicin and mitoxantrone with the omission of nonintercalating agents. Depending on whether molecular relapses were classified as censored or uncensored events, the 3-year Kaplan-Meier estimates of relapse-free survival (RFS) for the combined series were 90 +/- 2% and 86 +/- 2%, respectively. Minor differences observed between the 2 patient cohorts were negligible. Multivariate regression analysis of RFS showed that initial leukocyte (WBC) and platelet counts were the only variables with independent prognostic value. The resulting predictive model for RFS demonstrated its capability of segregating patients into low-risk (WBC count </= 10 x 10(9)/L, platelet count > 40 x 10(9)/L), intermediate-risk (WBC count </= 10 x 10(9)/L, platelets </= 40 x 10(9)/L), and high-risk (WBC count > 10 x 10(9)/L) groups, with distinctive RFS curves (P <.0001). The conclusions are that omission of nonanthracycline drugs from the AIDA regimen is not associated with reduced antileukemic efficacy and a simple predictive model may be used for risk-adapted therapy in this disease. (Blood. 2000;96:1247-1253)

Adolescent↗

Aluminum toxicity. Hematological effects.

Sequential effects of intoxication with aluminum hydroxide (Al) (80 mg/Kg body weight, i.p., three times a week), were studied on rats from weaning and up to 28 weeks. The study was carried out on hematological and iron metabolism-related parameters on peripheral blood, at the end of the 1st, 2nd, 3rd, 4th, 5th and 6th months of exposure. As it was described that hematotoxic effects of Al are mainly seen together with high levels of uremia, renal function was measured at the same periods. The animals treated developed a microcytosis and was accompanied by a decrease in mean corpuscular hemoglobin (MCH). Significantly lower red blood cell counts (RBC million/microl) were found in rats treated during the 1st month. These values matched those obtained for control rats during the 2nd month. From the 3rd month onwards, a significant increase was observed as compared to control groups, and the following values were obtained by the 6th month: (T) 10.0 +/- 0.3 versus (C) 8.7 +/- 0.2 (million/microl). Both MCH and mean corpuscular volume (MCV) were found to be significantly lower in groups treated from the 2nd month. At the end of the 6th month the following values were found: MCH (T) 13.3 +/- 0.1 versus (C) 16.9 +/- 0.3 (pg); MCV (T) 42.1 +/- 0.7 versus (C) 51.8 +/- 0.9 (fl). Al was found responsible for lower serum iron concentration levels and in the percentage of transferrin saturation. Thus, although microcytic anemia constitutes an evidence of chronic aluminum exposure, prolonged exposure could lead to a recovery of hematocrit and hemoglobin concentration values with an increase in red cell number. Nevertheless, both microcytosis and the decrease of MCH would persist. These modifications took place without changes being observed in the renal function during the observation period.

Aluminum Hydroxide↗

Reduced thrombus burden with abciximab delivered locally before percutaneous intervention in saphenous vein grafts.

BACKGROUND: Existing thrombus can complicate percutaneous saphenous vein graft (SVG) intervention. Local delivery of thrombolytics has been used to reduce the thrombus burden often associated with these interventions. We sought to determine whether local delivery of a platelet glycoprotein IIb/IIIa inhibitor is feasible and can reduce thrombus burden before percutaneous SVG intervention. METHODS: We performed a multicenter pilot study of abciximab (0.25 mg/kg) given by local delivery catheter before percutaneous intervention for de novo SVG stenoses followed by intravenous infusion. All patients (n = 58) had >/=60% stenosis and Thrombolysis In Myocardial Infarction (TIMI) grade >0 flow in an SVG of 3 to 4 mm in diameter. Percent diameter stenosis, TIMI thrombus grade, and TIMI flow grade were measured before and after delivery of abciximab and after intervention. RESULTS: Median percent diameter stenosis improved from 69% to 45% (P =.0001) after local delivery, and TIMI thrombus grade >/=1 incidence reduced from 68% to 34% (P =.0001). TIMI flow grade was not significantly affected (P =.12). All patients had a successful intervention (</=50% residual stenosis). CONCLUSIONS: Local abciximab delivery before percutaneous SVG intervention is associated with significantly reduced thrombus burden, significantly improved percent diameter stenosis, and excellent acute procedural results. Further studies of this approach are warranted to define its clinical utility.

Abciximab↗

Prophylaxis of supraventricular and ventricular arrhythmias after coronary artery bypass grafting with low-dose sotalol.

BACKGROUND: Supraventricular tachyarrhythmia (SVT) commonly occurs shortly after coronary artery bypass grafting (CABG), but ventricular arrhythmias are less documented. METHODS: On the 1st postoperative day, 206 consecutive eligible patients were prospectively randomized to a sotalol group (80 mg b.i.d.; n = 103) or a control group without beta-blockade or antiarrhythmic drugs (n = 103). RESULTS: The SVT incidence (predominantly atrial fibrillation) accounted for 16% in the sotalol group versus 48% (p < 0.00001). Multivariate analysis showed that sotalol reduced the SVT incidence (p < 0.00001, odds ratio, 0.20; 95% confidence interval, 0.09 to 0.42), whereas a lower preoperative left ventricular ejection fraction (p = 0.019) and older age (p = 0.031) were independent risk factors of SVT occurrence. The Holter electrocardiographic analysis (24 hours) demonstrated that sotalol (32 versus 92; p = 0.031) decreased the median number of ventricular events, mostly isolated premature ventricular beats. Neither ventricular proarrhythmia effect nor "torsades de pointes" were detected. Despite strict hemodynamic-based selection, sotalol had to be discontinued in 8 patients (7.8%), for reasons related to asthma in 3 or cardiac reasons in 5. CONCLUSIONS: Oral low-dose sotalol provided considerable and reliable protection in selected nondepressed cardiac function patients, reducing the occurrence of both supraventricular and ventricular arrhythmias after CABG.

Administration, Oral↗

Effective prevention of atrial fibrillation by continuous atrial overdrive pacing after coronary artery bypass surgery.

OBJECTIVES: The present study was aimed to evaluate the efficacy of a specific algorithm with continuous atrial dynamic overdrive pacing to prevent atrial fibrillation (AF) after coronary artery bypass graft (CABG) surgery. BACKGROUND: Atrial fibrillation occurs in 30% to 40% of patients after cardiac surgery with a peak incidence on the second day. It still represents a challenge for postoperative prevention and treatment and may have medical and cost implications. METHODS: Ninety-six consecutive patients undergoing CABG for severe coronary artery disease and in sinus rhythm without antiarrhythmic therapy on the second postoperative day were randomized to have or not 24 h of atrial pacing through temporary epicardial wires using a permanent dynamic overdrive algorithm. Holter ECGs recorded the same day in both groups were analyzed to detect AF occurrence. RESULTS: No difference was observed in baseline data between the two study groups, particularly for age, male gender, history of AF, ventricular function, severity of coronary artery disease, preoperative beta-adrenergic blocking agent therapy or P-wave duration. The incidence of AF was significantly lower (p = 0.036) in the paced group (10%) compared with control subjects (27%). Multivariate analysis showed AF incidence to increase with age (p = 0.051) but not in patients with pacing (p = 0.078). It decreased with a better left ventricular ejection fraction only in conjunction with atrial pacing (p = 0.018). CONCLUSIONS: We conclude that continuous atrial pacing with an algorithm for dynamic overdrive reduces significantly incidence of AF the second day after CABG surgery, particularly in patients with preserved left ventricular function.

Adult↗

Disseminated mycoses in a dog by Paecilomyces sp.

We describe a case of canine mycoses initially diagnosed by clinical signs and enzyme-linked immunosorbent assay anti-fungal test, and later confirmed by the isolation of Paecilomyces sp. during the post-mortem examination. The fungus was isolated from lesions in the kidneys, mitral valve, abdominal aorta and vertebral discs. In this kind of process, it is important to identify the responsible agent early in order to make a study of anti-fungal susceptibility and establish effective treatment.

Animals↗

Recovery of sensibility after digital neurorrhaphy: a clinical investigation of prognostic factors.

A multicenter retrospective review of 172 epineural digital nerve repairs using microsurgical techniques was performed. A total of 71 men and 25 women ranged in age from 5 to 64 years (mean age, 33.3 years). Sharp injuries occurred in 55.6% of patients and mild crush occurred in 44.4%. Isolated nerve injuries occurred in only 24.6% of patients. The majority of digital nerve injuries involved other structures: flexor tendons (33.5%), tendons and fractures (9.0%), and fractures (4.2%). Replantations were performed in 18 digits (21.6%) and revascularizations in 7 digits (7.2%). Injury to repair was less than 1 day in 47.8%, 2 to 7 days in 22.6%, 8 to 30 days in 23.3%, and 31 to 300 days in 6.3%. Follow-up averaged 22.2 months (range, 6-77 months). The authors found a significant correlation between age and recovery of sensibility as measured by Weber's two-point discrimination test (p < 0.001). Patients older than 40 years demonstrated significantly poorer recovery of sensibility than patients younger than 40 years. A trend of better sensibility return was noted in the younger age decades (<40) with declining age; however, the intergroup differences were not significant. There was also a significant correlation between severity of injury and recovery of sensibility (p < 0.001). Sharp injuries (8.2 mm) demonstrated significantly improved recovery of sensibility compared with mild crush (10.8 mm). Fractures (11.1 mm), fractures and tendon involvement (11.4 mm), and replantations (11.8 mm) demonstrated significantly diminished recovery of sensibility compared with isolated nerve injuries (7.9 mm), tendon involvement (8.1 mm), and revascularizations (9.3 mm). There did not appear to be any significant difference in recovery of sensibility according to gender, digit involved, radial or ulnar side of digit, median or ulnar nerve distribution, level of injury (except for the metacarpophalangeal joint and the distal palmar crease where most replantations occurred), or time interval from injury to repair. There was a weak negative correlation between length of follow-up and recovery of sensation.

Adolescent↗

Duodenojejunitis: is it idiopathic or is it Henoch-Schönlein purpura without the purpura?

BACKGROUND: Henoch-Schönlein purpura is a small-vessel vasculitic disease that most often affects the skin. Gastrointestinal manifestations have been well described, including duodenojejunal inflammation (DJI). METHODS: Four children with DJI and clinical features of HSP are described, in whom the rash was either not present or appeared atypically late in the illness. RESULTS: The characteristic rash did not develop in three children, and it developed much later in one. The patients (three boys and one girl) were aged between 7 and 9 years (mean, 7.5 years). Growth characteristics were normal. In all patients, pain occurred acutely with colicky abdominal pain in the spring or fall of the year, and all stools were positive for occult blood. No infectious cause was identified. Upper gastrointestinal endoscopic examinations demonstrated significant visual and histologic duodenitis in a pattern consistent with previous reports in children with known HSP. Factor XIII activity was absent. Immunoglobulin A levels were increased in three of four children. All children made a prompt recovery with the administration of intravenous glucocorticoids. In one child, the characteristic rash of HSP developed 18 weeks after the initial examination. CONCLUSION: Duodenojejunal inflammation may be the primary manifestation of HSP, even in the absence of the characteristic rash.

Anti-Inflammatory Agents↗

The cytotoxic enterotoxin of Aeromonas hydrophila induces proinflammatory cytokine production and activates arachidonic acid metabolism in macrophages.

An aerolysin-related cytotoxic enterotoxin (Act) of Aeromonas hydrophila possesses multiple biological activities, which include its ability to lyse red blood cells, destroy tissue culture cell lines, evoke a fluid secretory response in ligated intestinal loop models, and induce lethality in mice. The role of Act in the virulence of the organism has been demonstrated. In this study, we evaluated the potential of Act to induce production of proinflammatory cytokines associated with Act-induced tissue injury and Act's capacity to activate in macrophages arachidonic acid (AA) metabolism that leads to production of eicosanoids (e.g., prostaglandin E(2) [PGE(2)]). Our data indicated that Act stimulated the production of tumor necrosis factor alpha and upregulated the expression of genes encoding interleukin-1beta (IL-1beta) and IL-6 in the murine macrophage cell line RAW264.7. Act also activated transcription of the gene encoding inducible nitric oxide synthase. Act evoked the production of PGE(2) coupled to the cyclooxygenase-2 (COX-2) pathway. AA is a substrate for PGE(2), and Act produced AA from phospholipids by inducing group V secretory phospholipase A(2). We also demonstrated that Act increased cyclic AMP (cAMP) production in macrophages. cAMP, along with PGE(2), could potentiate fluid secretion in animal models because of infiltration and activation of macrophages resulting from Act-induced tissue injury. After Act treatment of RAW cells, we detected an increased translocation of NF-kappaB and cAMP-responsive element binding protein (CREB) to the nucleus using gel shift assays. Act also upregulated production of antiapoptotic protein Bcl-2 in macrophages, suggesting a protective role for Bcl-2 against cell death induced by proinflammatory cytokines. The increased expression of genes encoding the proinflammatory cytokines, COX-2, and Bcl-2 appeared correlated with the activation of NF-kappaB and CREB. This is the first report of the detailed mechanisms of action of Act from A. hydrophila.

Aeromonas hydrophila↗

Safety and immunogenicity of a paediatric presentation of an influenza vaccine.

BACKGROUND: Flu vaccination in otherwise healthy infants and young children is important to prevent severe disease, as well as to control epidemic spread of influenza infection. AIMS: To examine the safety and immunogenicity of a paediatric presentation of a purified, inactivated, triton split influenza vaccine. METHODS: Two doses of the vaccine, provided in prefilled syringes of 0.25 ml, were administered, one month apart, to 67 children under 3 years of age. RESULTS: Nine cases of immediate reaction to vaccination (macules/papules) were observed after the second injection only. During the study period, 9% of children experienced at least one delayed local reaction, and 28% of children presented at least one systemic reaction. Almost all reactions were mild and transient. Immunogenicity results surpassed the European Community recommendations for a 0.50 ml dose of vaccine in adults. CONCLUSION: This paediatric formulation of inactivated flu vaccine appears safe and immunogenic in children from 6 months to 3 years of age; the convenient presentation in a prefilled syringe of 0.25 ml volume will facilitate administration of the dose recommended for young children.

Antibodies, Viral↗

Determinants of glucose toxicity and its reversibility in the pancreatic islet beta-cell line, HIT-T15.

HIT-T15 cells, a clonal beta-cell line, were cultured and passaged weekly for 6 mo in RPMI 1640 media containing various concentrations of glucose. Insulin content decreased in the intermediate- and late-passage cells as a continuous rather than a threshold glucose concentration effect. In a second series of experiments, cells were grown in media containing either 0.8 or 16.0 mM glucose from passages 76 through 105. Subcultures of passages 86, 92, and 99 that had been grown in media containing 16.0 mM glucose were switched to media containing 0.8 mM glucose and also carried forward to passage 105. Dramatic increases in insulin content and secretion and insulin gene expression were observed when the switches were made at passages 86 and 92 but not when the switch was made at passage 99. These findings suggest that glucose toxicity of insulin-secreting cells is a continuous rather than a threshold function of glucose concentration and that the shorter the period of antecedent glucose toxicity, the more likely that full recovery of cell function will occur.

Cell Division↗