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Biomedical subjects

B Sanchez

Publications and source records attributed to B Sanchez.

At least 37 records · Page 2Linked to original sources

Effects of novel anti-inflammatory compounds on healing of acetic acid-induced gastric ulcer in rats.

Nonsteroidal anti-inflammatory drugs often cause development of significant GI lesions. Selective inhibitors of prostaglandin G/H synthase/cyclooxygenase-2 (PGHS-2) enzyme and some dual inhibitors of PGHS/5-lipoxygenase (5-LO) enzymes have been reported to be potent anti-inflammatory compounds that carry a much lower risk of having GI irritating effects. We have evaluated the anti-inflammatory effect and the GI safety profile of three new anti-inflammatory compounds: the selective PGHS-2 inhibitors NS-398 and PD 138387 and the PGHS/5-LO dual inhibitor PD 137968. All the compounds tested showed an anti-inflammatory activity in the carragenan footpad edema test in rats. None of these compounds caused either gastric damage 4 h after p.o. administration of 100 mg/kg in rats or inhibition of PGE2 synthesis in the stomach. However, when administered p.o. at an effective anti-inflammatory dose to rats with pre-existing acetic acid-induced gastric ulcer, NS-398 caused a statistically significant delay of ulcer healing. No impairment of the ulcer healing was observed with the other compounds evaluated. Derivatives of 2,6-di-tert-butylphenol, whose members may act as PGHS-1/PGHS-2 inhibitors, selective PGHS-2 inhibitors or PGHS/5-LO dual inhibitors, are novel anti-inflammatory compounds that are devoid of GI irritating effects and do not affect the rate of pre-existing gastric ulcer healing.

Acetic Acid↗

Melatonin induces hyporeactivity caused by type II collagen in peripheral blood lymphocytes from patients with autoimmune hearing losses.

We have studied the behavior of peripheral blood lymphocytes in healthy controls and in patients with various hearing losses. These hearing losses were of an autoimmune origin in which type II collagen and melatonin were either present or absent, activated or not with concanavalin A (Con A). In patients with autoimmune hearing losses, the results showed lymphocytes that displayed hyporeactivity to type II collagen in terms of their proliferative activity in the presence of Con A. The hyporeactivity is specially relevant in those cells which are melatonin incubated. When different nosologic entities were studied, we observed similar lymphocyte hyporeactivity to type II collagen in bilateral sensorineural hearing loss, Ménière's disease and otosclerosis. We conclude that in the lymphocytes of patients with autoimmune hearing losses, there is hyporeactivity to type II collagen when compared to the hyporeactivity of lymphocytes in control groups. This hyporeactivity is revealed when the lymphocytes are activated in the presence of melatonin.

Adolescent↗

Detection of hyperdiploid malignant cells in body cavity effusions by fluoresence in situ hybridization on ThinPrep slides.

BACKGROUND: Benign body cavity effusions sometimes cannot be distinguished from malignant ones by conventional cytology. The authors performed fluorescence in situ hybridization (FISH) on ThinPrep slides using chromosome specific probes to see if hyperdiploid malignant cells could be detected in 20 body cavity effusions. The results were then compared with those of conventional cytology. METHODS: A total of 20 body cavity effusions from 19 patients were studied using conventional cytology and FISH. Probes specific for chromosomes 3, 8, 10, and 12 were used to detect hyperdiploidy on ThinPrep slides (Cytyc Corporation, Boxborough, MA). RESULTS: A total of 13 patients had malignant conditions (either prior history of malignancy or the presence of malignancy anywhere in the body). Conventional cytology and FISH were both positive in 5 of these patients (6 samples) and negative in 2 patients. The results for one sample were inconclusive by both methods. There were 5 discrepant cytology-FISH results in patients with malignant conditions. One sample was positive by FISH and negative by cytology, one was positive by FISH and "atypical" by cytology, and three were inconclusive by FISH and negative by cytology. FISH results were either negative (in 4 samples) or inconclusive (in 2 samples) in the 6 patients with benign conditions. CONCLUSIONS: FISH can detect hyperdiploid malignant cells in body cavity effusions and is especially useful when the major cell population consists of malignant cells that cannot be differentiated from mesothelial or "atypical" cells. It is less useful in detecting a small population of malignant cells hidden in an inflammatory or reactive cell background. More studies are needed to establish diagnostic criteria further and to assess the clinical usefulness of this procedure.

Adult↗

Comparison of the bonding power of various autologous fibrin tissue adhesives.

OBJECTIVE: Three known autologous fibrin tissue adhesives were evaluated for bonding power on Silastic and animal and human tissues. These adhesives were also injected into living tissue to determine if any of these fibrin glues cause inflammatory or deleterious reactions when kept in living tissue for a sustained period. METHODS: In Part I of our study, blood was drawn from 59 healthy volunteers, and autologous fibrin tissue adhesives were manufactured using the cryoprecipitation (AFTA-C), ammonium sulfate (AFTA-A), and ethanol/freezing (AFTA-E) methods. Blocks were then prepared using Silastic, porcine dermis, and human dura mater and bonded together for 10 or 30 minutes using the three adhesives. The blocks were then separated while bonding power was measured. In Part II of our study, 0.01 mL AFTA-C, AFTA-A, or AFTA-E was injected subcutaneously into the auricles of 60 rats. The rats were then killed 3, 7, 14, or 21 days later, and the auricles were examined histologically for signs of toxicity. RESULTS: The bonding powers of AFTA-E and AFTA-C were found to be statistically similar, and both were statistically stronger than AFTA-A. The injection of AFTA-A, AFTA-E, and AFTA-C into rat auricles did not cause any adverse effects. CONCLUSIONS: All three methods for manufacturing AFTA are effective in producing a reliable, stable fibrin glue. However, AFTA-E and AFTA-C demonstrate stronger bonding power than AFTA-A. In addition, all three forms of AFTA produce no undesirable tissue changes when injected into rat auricles.

Animals↗

Evaluation of pooled fibrin sealant for ear surgery.

HYPOTHESIS: This study investigated the bonding strength and tissue toxicity of a commercially prepared dual-virally-inactivated pooled-blood fibrin tissue adhesive (ViGuard-FS; Melville Biologics, Inc., NY, U.S.A.) and compared it with an autologous fibrin tissue adhesive made by the precipitation of fibrinogen using ethanol and freezing (AFTA-E). METHODS: The bonding strength of FS was optimized by varying the concentrations of fibrinogen and human or bovine thrombin using three different surface media: inorganic (silastic), animal skin, and human dura mater. Furthermore, tissue reactions and duration of fibrin clots were studied by injecting FS into the auricles of rats. RESULTS: This study showed that optimized FS with human thrombin was superior in bonding strength to AFTA-E on all three surface media, and that FS does not produce any toxic tissue responses when injected into rat auricles. Minimal traces of the adhesive clot could be observed in a few auricles at 35 days after application. CONCLUSIONS: Because it is made from pooled-donor blood that has been treated with virus elimination procedures, FS is superior to autologous fibrin tissue adhesive in which fibrinogen is precipitated by the ethanol/freezing method. FS has not shown any undesirable tissue reactions when injected into live rat auricles. We believe that these results provide a rationale for further clinical development of ViGuard-FS as a tissue adhesive for otologic surgery.

Animals↗

Increased gastroduodenal concentrations of transforming growth factor alpha in adaptation to aspirin in monkeys and rats.

BACKGROUND & AIMS: The mechanism by which gastric mucosa becomes more resistant to damage by repeated aspirin administration is not known. Transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) prevent drug-induced gastric injury. The aim of this study was to determine whether gastroduodenal tissue levels of TGF-alpha and EGF protein were altered during adaptation to aspirin-induced injury in monkeys and rats in vivo. METHODS: Animals were given aspirin daily for up to 28 days. Gross mucosal injury was assessed by computerized image analysis in rats and by endoscopy in monkeys. Mucosal concentrations of TGF-alpha and EGF were quantitated by radioimmunoassays from endoscopic biopsy samples in monkeys and from scraped mucosa in rats. RESULTS: Long-term administration of aspirin caused a significant increase in gastric and duodenal tissue levels of TGF-alpha in monkeys and rats; the increased levels of TGF-alpha significantly correlated with the decrease in aspirin-induced injury. No change in the gastroduodenal tissue levels of EGF was observed. Adaptation was not associated with any significant change in basal gastric acid secretion in monkeys and occurred despite a significant decrease in gastric mucin in rats. CONCLUSIONS: Adaptation of the gastric mucosa to the damaging effect of aspirin is associated with a significant and specific increase in TGF-alpha protein in the gastroduodenum.

Adaptation, Physiological↗

Peripheral effects of opioids in a model of intestinal inflammation in mice.

The study evaluates the peripheral component of the antitransit effects of opioids during acute intestinal inflammation induced by the intragastric administration of croton oil (CO) in mice. Gastrointestinal transit was measured 3 h after CO or saline (SS) administration with a charcoal meal. In both groups, the effects of mixed (morphine, fentanyl, U-50488H) and peripherally acting (N-methylmorphine, PL017, ICI-204448) opioids and their antagonism by naloxone and naloxone methiodide were established. During inflammation, the potencies of morphine and N-methylmorphine increased 3 times, and those of fentanyl and PL017, 1.9 times. The effects were reversed by naloxone (0.1 mg/kg) and naloxone methiodide (0.3 mg/kg). No dose-response relationships could be elicited with U-50488H or ICI-204448, and their antitransit effects were analogous in SS- and CO-treated animals. These results show that during inflammation the enhanced antitransit effects of opioids are primarily mediated by interaction with opioid receptors located at peripheral sites. In addition, inflammation of the gut seems to induce a sensitization of mu-but not kappa-opioid receptors.

Animals↗

An autologous fibrin tissue adhesive with greater bonding power.

OBJECTIVE: To describe and evaluate an autologous fibrin tissue adhesive (AFTA) that uses a combination of ethanol and freezing to precipitate fibrinogen (AFTA-E). DESIGN: The bonding power of AFTA-E was compared with that of a conventional AFTA based on ammonium sulfate precipitation of fibrinogen (AFTA-A). In this study, Silastic, porcine dermis, and human dura mater blocks were bonded together for 10 and 30 minutes with AFTA-E or AFTA-A. The blocks were then separated and the bonding power was measured. The efficacy of AFTA-E was also evaluated after a 24-hour refrigeration. SETTING: The Department of Otolaryngology Research Laboratory at the University of Illinois Eye and Ear Infirmary, Chicago, Ill. PARTICIPANTS: Blood was drawn from 86 healthy volunteers and AFTA-E and/or AFTA-A was manufactured. RESULTS: The AFTA-E was shown statistically to bond stronger than the AFTA-A. In addition, it was found that the efficacy of AFTA-E was unchanged after a 24-hour refrigeration. CONCLUSIONS: The improved AFTA, AFTA-E, is a superior alternative to the conventional AFTA-A. Furthermore, AFTA-E can be manufactured before surgery and stored, thus minimizing preparation time during surgery.

Adhesiveness↗

BPC-15 reduces trinitrobenzene sulfonic acid-induced colonic damage in rats.

The effect of BPC-15 (Booly Protection Compound-15) was evaluated in a rat model of colonic injury. A single intracolonic administration of trinitrobenzene sulfonic acid (TNBS) dissolved in ethanol induces severe colonic damage, which is characterized by areas of necrosis surrounded by areas of acute inflammation. The damage is associated with high myeloperoxidase (MPO) activity, mainly as a reflection of neutrophilic infiltration into the damaged tissue. In this study, 1 hr before a single intracolonic administration of 50 mg/kg of TNBS in 50% ethanol, the animals were treated with one of the following doses of BPC-15: 0.0001, 0.001, 0.01, 0.1, 1 or 10 nmol/kg administered i.p. or with a dose of 10 nmol/kg administered intracolonically. The animals were sacrificed 3 days later and the extent of colonic necrosis and hyperemia was measured with an image analyzer. The i.p. administration of BPC-15 significantly reduced the extent of TNBS-induced colonic damage in a dose-dependent manner. This was associated with a statistically significant and dose-dependent reduction in colonic tissue MPO activity. At the dose tested (10 nmol/kg), intracolonic administration of BPC-15 did not significantly reduce either the extent of the colonic damage or the increase in MPO activity induced by TNBS. In conclusion, this study showed that i.p. administration of BPC-15 reduced TNBS-induced colonic damage in rats.

Amino Acid Sequence↗

[Severe pulmonary hypertension complicating a long treatment with dexfenfluramine].

The authors report a case of severe pulmonary hypertension after long-term dexfenfluramine treatment in a 48 year old man with no previous medical history. Dexfenfluramine, which has previously been reported to cause pulmonary hypertension, is an amphetamine-like anorexic agent, a pharmacological group known to predispose to this type of side effect. The possibility of this complication should be born in mind before prescribing the drug. In particular, it would seem to be particularly important not to exceed the recommended length of treatment especially as potential reversibility of pulmonary hypertension on withdrawal of the drug has been reported in one case.

Dose-Response Relationship, Drug↗

Lymphocyte subpopulations in patients with primary fibromyalgia.

OBJECTIVE: Fibromyalgia (FM) is a clinical entity of unknown etiology frequently diagnosed in rheumatology. The potential involvement of the immune system in its pathogenesis has been suggested. Studies of abnormal T cell subpopulations often have been inconclusive. We attempted to clear this point by comparing lymphocyte subpopulations, including some of the newer activation markers, in patients with FM and healthy controls. METHODS: Sixty-five patients with FM and 56 healthy controls were studied. Flow cytometry was used as a quantification technique to measure lymphocyte subpopulations, CD3 (T cells), CD19 (B cells), CD16 (natural killer cells), CD4 (T helper/inducer cells), CD8 (T cytotoxic/suppressor cell), CD25 (interleukin 2 receptor), CD69 (activation inducer molecule marker), CD71 (transferrin receptor) and CD54 (ICAM-1); CD4/CD8 ratios were also estimated. RESULTS: The number of T cells expressing activation markers CD69 and CD25 was decreased in patients with FM; the other subpopulations were similar in patients and controls. CONCLUSION: Our results suggest a defect in T cell activation in patients with FM.

Adolescent↗

[Cardiac tamponade in severe hypothyroidism. A rare cause].

Pericardial effusion frequently occurs in patients with hypothyroidism, and this fully justifies the use of echocardiography at the time of diagnosis and during the follow-up of hypothyroidism. Signs indicating that the pericardial effusion is poorly tolerated are rare, and the development of pericardial tamponade is exceptionally reported. A case of tamponade in an elderly woman with severe hypothyroidism is described here. Some physiopathological particularities are emphasized, together with the value of echocardiography for the diagnosis and that of pericardial drainage for the treatment.

Aged↗

Association of HLA-DR4-Dw15 (DRB1*0405) and DR10 with rheumatoid arthritis in a Spanish population.

OBJECTIVE: To analyze the associations of HLA class II antigens with rheumatoid arthritis (RA) in a Spanish population. METHODS: We used DNA oligotyping to determine DR types, DQA1 and DQB1 alleles, and DR4 variants in 70 unrelated seropositive RA patients and 189 healthy controls living in Spain. RESULTS: A significantly higher frequency of DR4 was seen in RA patients compared with controls (relative risk [RR] = 2.40). The DR10 specificity correlated most strongly with disease susceptibility (RR = 3.84). A significant decrease in the frequency of DR7 was observed in the RA patients (RR = 0.48). DR4-Dw15 (DRB1*0405) was found to be the unique DR4 allele associated with RA (RR = 4.27, P < 0.05), whereas Dw4 (DRB1*0401) and Dw14 (DRB1*0404/0408) showed no association, and both Dw10 (DRB1*0402) and Dw13 (DRB1*0403/0407) were negative risk factors for the disease. Approximately one-third of the cases of RA could not be explained by the "shared epitope" hypothesis. Investigation of the DQ alleles associated with DR4 showed that the haplotype Dw15-DQ8 (DRB1*0405-DQB1*0302) was a susceptibility factor for RA (RR = 6.36, P < 0.05). CONCLUSION: Our results suggest that HLA class II alleles involved in RA susceptibility can vary among different Caucasian populations.

Alleles↗

Bilateral distribution of aminopeptidase activities in selected structures of a photoneuroendocrine circuit and other rat brain areas.

Provided that soluble aminopeptidases, the most abundant proteolytic enzymes found in brain, are involved in the metabolism of several neuropeptides, their activity could be a reflect of neuropeptide function. Therefore, in order to analyze their rate of participation, we have measured 4 soluble aminopeptidase activities: leucine aminopeptidase, arginine aminopeptidase, aspartate aminopeptidase, and pyroglutamate aminopeptidase, using arylamide derivatives as substrates, in selected structures integrating the photoneuroendocrine circuit related to the melatonin rhythm generating system and other rat brain areas. The regional distribution of all the activities was heterogenous: a 3-fold (leucine-, arginine- and aspartate-aminopeptidase) and 5-fold (pyroglutamate aminopeptidase) difference was observed between the regions with the highest and lowest activity. Significant differences were displayed between the left and right retina for pyroglutamate aminopeptidase and arginine aminopeptidase activities. High levels of pyroglutamate aminopeptidase were evident in the retina and adenohypophysis, which is consistent with a role for thyrotropin releasing hormone in photoreceptive mechanisms, and support its well established role in controlling thyrotropin releasing hormone in anterior pituitary. The presence of a high activity rate of aspartate aminopeptidase in adenohypophysis implies an active participation of angiotensin peptides at this level.

Aminopeptidases↗

A human monoclonal autoantibody to a nucleolar structure.

Peripheral blood lymphocytes from a scleroderma patient (CDC) were isolated, transformed with Epstein-Barr virus and fused to the heteromyeloma SHM-D33. Supernatants from cultures were screened for autoantibody production against nucleoprotamine by ELISA. Positive wells were cloned by limiting dilution. After cloning, supernatants from two wells were positive for the nucleoprotamine assay. One named CDC-1 has been studied in our laboratory. CDC-1 recognized a nucleolar antigen by indirect immunofluorescence. By using an ELISA with purified recombinant antigens, CDC-1 reacted against Ro/SS-A, U1 (RNP) and Sm. By immunoblotting using a lysate of MOLT-4 cell line, CDC-1 was able to react against a structure of 60 kD. When the antigen recognized by CDC-1 was purified, SDS-PAGE under reducing conditions with purified antigen and subsequent silver staining of the gel allowed us to detect three bands at 60, 55 and 39 kD, respectively. A screening by ELISA with previously characterized antisera against our purified antigen demonstrated reactivity of the CDC-1 antigen with those antisera able to recognize Ro/SS-A.

Antibodies, Antinuclear↗

Production of heterohybridomas secreting autoreactive and polyreactive human monoclonal antibodies.

Peripheral blood lymphocytes from two polytransfused renal dialysis patients were transformed by Epstein-Barr virus, fused to a heteromyeloma and cloned. Eight human monoclonal antibodies from the resulting clones were tested for their binding to a variety of antigens by ELISA, indirect immunofluorescence and immunoblotting. Antigens tested included B-cell lines, T and B lymphocytes, red blood cells, chronic lymphocytic leukaemic B cells, IgG, ssDNA, dsDNA, histones, nucleoprotamine, sperm nuclei, thymus and spleen extracts, MOLT4 cell lysates, affinity purified autoantigens, tetanus toxoid, bacterial lipopolysaccharide, insulin, and a tissue section screen. These human monoclonal antibodies reacted with more than one antigen to varying degrees and were autoreactive and polyreactive. One of these heterohybridoma cell lines exhibited cytoplasmic staining with an anti-CD5 monoclonal. Our findings support the concept that in adult individuals a subset of B cells produce heterogeneous IgM antibodies which can bind to a variety of different autoantigens and also to foreign antigens. These monoclonals were different from the autoantibodies usually seen in renal dialysis patients in the sense that they were not lymphocytotoxic.

Antibodies↗