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Biomedical subjects

J Contreras

Publications and source records attributed to J Contreras.

At least 19 recordsLinked to original sources

Effect of sildenafil on non-adrenergic non-cholinergic neurotransmission in bovine penile small arteries.

The purpose of the present study was to investigate the effect of the phosphodiesterase isoenzyme V inhibitor, sildenafil, on non-adrenergic non-cholinergic neurogenic relaxations of intracavernous isolated penile small arteries. Dense plexes of nerve fibres immunoreactive for neural nitric oxide (NO) synthase were observed in the adventitia-media junction of the penile small arteries. In 5-hydroxytryptamine-contracted preparations, the inhibitor of NO synthase, N(G)-nitro-L-arginine (L-NOARG), and of soluble guanylyl cyclase, 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ), reduced the electrical field stimulation-induced relaxations. Sildenafil and exogenous NO induced relaxations of penile small arteries. Sildenafil enhanced NO and vasoactive intestinal peptide-induced relaxations. Moreover, sildenafil increased the duration of the relaxations elicited by electrical field stimulation in penile small arteries and corpus cavernosum tissue. In the presence of L-NOARG, sildenafil only at supratherapeutic concentrations reduced the prazosin-sensitive contractions elicited by EFS in penile small arteries. Neurogenic NO-mediated and guanylyl cyclase-dependent relaxations of penile small arteries and corpus cavernosum tissue, considered to be associated with the vasodilatation leading to erection, are selectively enhanced by an inhibitor of phosphodiesterase V.

3',5'-Cyclic-GMP Phosphodiesterases↗

The safety and efficacy of a two-dose daclizumab (zenapax) induction therapy in liver transplant recipients.

BACKGROUND: Induction therapy with daclizumab has been shown to be efficacious in the prevention of acute rejection in kidney transplant patients. The routine use of antibody induction therapy in liver transplantation has not gained widespread acceptance, except in the cases of renal insufficiency. The recent approval of daclizumab prompted us to initiate this pilot study using induction therapy in those patients at risk for developing posttransplant renal insufficiency. METHODS: This nonrandomized study examined the use of daclizumab in 39 of the last 97 liver transplants performed at the University of Alabama in Birmingham. The daclizumab group received 2 mg/kg intravenously before organ engraftment, and 38 of the 39 received 1 mg/kg intravenously on postoperative day 5. The control group consisted of the remaining 58 contemporary patients. Additional immunosuppression consisted of steroids, tacrolimus, or microemulsion cyclosporine in all patients and mycophenolate mofetil in selected patients. RESULTS: Pretransplant demographics were not significantly different between the groups. In the induction group there were significantly fewer males, 14 (36%) vs. 34 (59%) (P=0.03). They had greater renal insufficiency at the time of transplant, serum creatine 1.9+/-0.37 mg/dl vs. 0.8+/-0.5; P=0.0009, and more patients were at higher acuity (status 1 and 2A): 12 (31%) vs. 3 (5%) P=0.0006 than in the noninduction group. By postoperative day 7, renal function improved in the induction group such that it was not significantly different from the noninduction group and remained similar throughout the rest of the follow-up. The induction group also experienced significantly less acute rejection, 7 (18%) vs. 23 (40%) (P=0.02) than in the noninduction group in the first 6 months. The 1-, 3-, and 6-month patient survival rates were similar in the induction group, 97.4%, 97.4%, and 97.4%, vs. non-induction 94.8%, 93.0%, and 93% (P=NS). The incidence of cytomegalovirus, in the first 6 months, in the induction group was four (10%) vs. five (9%) (P=NS) in the noninduction group. CONCLUSION: In the pilot study, induction therapy with daclizumab was safe, facilitated improvement in renal function, and appeared to reduce the incidence of acute rejection. Combination therapy with daclizumab may be an important adjunct in immunosuppressive strategies for liver transplant recipients.

Adult↗

Hypersensitivity of malignant hyperthermia-susceptible swine skeletal muscle to caffeine is mediated by high resting myoplasmic [Ca2+ ].

BACKGROUND: Malignant hyperthermia (MH) is an inherited pharmacogenetic syndrome that is triggered by halogenated anesthetics and/or depolarizing muscle relaxants. MH-susceptible (MHS) skeletal muscle has been shown to be more sensitive to caffeine-induced contracture than muscle from nonsusceptible (MHN) subjects and is the basis for the most commonly used clinical diagnostic test to determine MH susceptibility. METHODS: We studied the effects of caffeine on myoplasmic free calcium concentration ([Ca2+]i) in MHN and MHS swine muscle fibers by means of Ca2+-selective microelectrodes before and after K+-induced partial depolarization. RESULTS: [Ca2+]i in untreated MHN fibers was 123 +/- 8 nm versus 342 +/- 33 nm in MHS fibers. Caffeine (2 mm) caused an increase in [Ca2+]i in both groups (296 +/- 41 nm MHN vs. 1,159 +/- 235 nm MHS) with no change in resting membrane potential. When either MHN or MHS, muscle fibers were incubated in 10 mm K+ [Ca2+]i transiently increased to 272 +/- 22 nm in MHN and 967 +/- 38 nm in MHS for 6-8 min. Exposure of MHN fibers to 2 mm caffeine while resting [Ca2+]i was elevated induced an increment in [Ca2+]i to 940 +/- 37 nm. After 6-8 min of exposure to 10 mm K+, [Ca2+]i returned to control levels in all fibers, and the effect of 2 mm caffeine on resting [Ca2+]i returned to control, despite continued partial membrane depolarization. CONCLUSIONS: These results suggest that the increased "sensitivity" to caffeine of MHS swine muscle fibers is a nonspecific response related, at least in part, to the high resting [Ca2+]i and not an increased caffeine sensitivity of the sarcoplasmic reticulum Ca2+ release channel per se.

Animals↗

Tachykininergic excitatory neurotransmission in the pig intravesical ureter.

PURPOSE: The present investigation was designed to study the role played by neurokinin A (NKA) in the non adrenergic non cholinergic (NANC) neurotransmission of the pig intravesical ureter. MATERIALS AND METHODS: We used immunohistochemical techniques to evidence the distribution of NKA-immunoreactive (NKA-IR) fibers in the pig intravesical ureter. We have also performed isolated organ bath experiments to release endogenous tachykinins from ureteral nerves and to characterize the functionally active receptor through which endogenous ligands evoke contraction, and to show the effect of exogenous tachykinins on intravesical ureteral smooth muscle. RESULTS: NKA-IR fibers were found penetrating through ureteral adventitia and distributed in the subepithelial and muscular layers. NKA-IR fibers were not found around small arteries supplying the ureter or in the associated intramural ganglia. Electrical field stimulation (EFS, 1 ms duration, 2 to 16 Hz, 20 s trains) performed in NANC conditions evoked frequency-dependent contractions which were reduced by capsaicin (10-5 M) and GR 94800 (3 x 10-8 M), sensory neurotoxin and NK2 receptor antagonist, respectively. Contractions to EFS were abolished by tetrodotoxin (10-6 M). Exogenous NKA and substance P (SP) induced dose-dependent contractions, characterized by an increase of the ureteral basal tone, NKA being more potent than SP. CONCLUSIONS: These results suggest that tachykinins, especially NKA, released from capsaicin-sensitive primary afferents, are involved in the NANC excitatory neurotransmission, contracting the smooth muscle via NK2 receptors activation, in the pig intravesical ureter. NKA at this level does not seem to participate in the regulation of local blood flow, plasmatic extravasation or ganglionar transmission.

Animals↗

Routes of entry of Piscirickettsia salmonis in rainbow trout Oncorhynchus mykiss.

Since 1989, Piscirickettsia salmonis, the causal agent of piscirickettsiosis, has killed millions of farmed salmonids each year in southern Chile. The portal of entry for the pathogen was investigated by use of selected experimental infections in juvenile rainbow trout (12 g). The methods used were intraperitoneal injection, subcutaneous injection, patch contact on skin, patch contact on gills, intestinal intubation and gastric intubation. Cumulative mortalities at Day 33 post-inoculation were 98, 100, 52, 24, 24, and 2%, respectively. It was shown that intact skin and gills could be penetrated by P. salmonis. The high mortality obtained in subcutaneously injected fish indicated that skin injuries could facilitate the invasion of this pathogen. Results suggested that the main entry sites are through the skin and gills and that the oral route may not be the normal method by which P. salmonis initiates infection of salmonids.

Administration, Topical↗

Chemical composition, digestibility and antinutritional factors content of two wild legumes: Styphonolobium burseroides and Acacia bilimekii.

The chemical composition, digestibility and toxin contents of two wild legumes: Styphnolobium burseroides and Acacia bilimekii, collected in a semi-arid zone of Mexico, were determined. Both legumes had a high fiber content. The seeds of Styphnolobium burseroides had a low protein content (14%), and the pod a high content of reducing sugars. However the seeds of Acacia bilimekii had a high protein concentration (35%). The seed proteins were low in sulphur amino acids and tryptophan in both legumes but were rich in lysine. Trypsin inhibitors and lectins were present in low concentrations; alkaloids and cyanogenic glucosides were not detected. The in vitro digestibility for monogastric animals was low but the same test with ruminal juice showed a high digestibility for both legumes. Based on their chemical composition and digestibility, these legumes could be a good alternative source in the feeding of ruminants.

Amino Acids↗

[Utility of 201Tl washout in syndrome X patients].

INTRODUCTION: The term Syndrome X defines a group of patients who present symptoms of typical angina pectoris, positive exercise test and normal coronaries in the arteriogram. This study aims to compare the results of 201Tl scan images and washout in Syndrome X patients. METHODS: 24 patients with typical angina and normal arteriogram and 30 normal controls were studied with 201Tl SPECT to evaluate uptake and washout. RESULTS: 201Tl perfusion defects were found in 3 out of 24 (12.5%) and washout defects in 22 out of 24 (91.6 %). There is a statistically significant reduction (0 < 0.05) in thallium uptake and washout in patients with syndrome X compared to the control group. In addition, patients with syndrome X had a higher thallium uptake at rest than during exercise compared to the healthy subjects. CONCLUSIONS: Analysis of the 201Tl washout and thallium uptake can provide addition information in the evaluation of patients with syndrome X since the visual assessment of the cardiac scintigraphy with 201Tl is of limited value. Alterations of the myocardial perfusion in patients with chest pain and normal coronaries can be detected non-invasively with a complete scintigraphic study.

Aged↗

Nitrergic relaxation of the horse corpus cavernosum. Role of cGMP.

The involvement of nitric oxide (NO) and the mechanisms mediating neurogenic relaxation were investigated in the horse corpus cavernosum. NADPH-diaphorase activity was expressed in nerve fibres around arteries and muscular bundles in the horse trabecular tissue. Relaxations in response to electrical field stimulation were tetrodotoxin (10(-6) M)-sensitive, indicating their neurogenic origin. The NO synthase inhibitor, L-NO-arginine (L-NO-Arg, 3 x 10(-5) M), abolished the electrically induced relaxations, which were significantly reversed by L-arginine (3 x 10(-3) M). Exogenous NO (10(-6)-10(-3) M) evoked relaxations which were unaffected by L-NO-Arg. 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, 5 x 10(-6) M), an inhibitor of guanylate cyclase activation by NO, reduced the relaxations in response to electrical stimulation and exogenous NO. Iberiotoxin (3 x 10(-8) M) or apamin (5 x 10(-7) M), inhibitors of large and small conductance Ca2+-activated K+ channels, respectively, and glibenclamide (3 x 10(-6) M), a blocker of ATP-sensitive K+ channels, failed to modify the relaxations with NO. It is suggested that NO is present in nerve fibres of the horse corpus cavernosum and relaxes smooth muscle through a guanylate cyclase-dependent mechanism. Neither Ca2+-activated nor ATP-sensitive K+ channels seem to be involved in these relaxations.

Adenosine Triphosphate↗

DR non-B1 mismatches influence allogeneic MLR-induced TH1- or TH2-like cytokine responses in rhesus monkeys.

Human and nonhuman primates have multiple DR B1 and non-B1 alleles. However, the role of mismatched DR non-B1 alleles in primary alloimmune responses is not well understood. Macaques, which share close DNA homologies with human MHC genes and have a high number of beta-chain genes in the DR subregion, are preeminent preclinical models for immunologic studies of transplant tolerance and immunosuppression. In this study, we examined the effect of allogeneic MHC Class II DRB mismatches in Th1- and Th2-like cytokine responses elicited in one-way MLR cultures in rhesus macaques. An ELISPOT method was used to estimate cytokine secretion at the single cell level. Molecular typing for DRB1 and DR non-B1 alleles was performed by a moderate-high resolution PCR-SSP method using a panel of 55 primer pairs covering 74 DRB alleles and clusters. Of 35 unrelated combinations, 66% had multiple (> or = 2) allelic MM at DRB1 and DR non-B1 with no significant correlation between numbers of DRB1 and DR non-B1 mismatches. Pairs with 1 or 0 MM were assigned to a mono/null MM group to obtain sufficient numbers for statistical analysis. The pairs differing by multiple vs. mono/null DRB1 MM showed no significant difference in cytokine prevalence (P = 0.69). In contrast, high IFN-gamma/ IL4 SFC ratios were noted in pairs with multiple vs. mono/null DR non-B1 MM (p = 0.0009). IFN-gamma/IL-10 spot forming cell (SFC) ratios were consistent with IFN-gamma/IL-4 SFC ratios (r = 0.98). Multiple DR non-B1 mismatches showed a trend towards higher MLR proliferative responses, although the stimulation index did not reflect the dominant cytokine response. These observations suggest a bias towards Th1-like cytokine production under allostimulation with multiple DR non-B1 gene products. Further study of the primary structure of DR non-B1 determinants may be helpful in understanding the fine molecular mechanisms governing the regulation of cytokine profiles during allostimulation in primates.

Animals↗

Synthesis and evaluation of tacrine-huperzine A hybrids as acetylcholinesterase inhibitors of potential interest for the treatment of Alzheimer's disease.

Seventeen polycyclic compounds related to tacrine and huperzine A have been prepared as racemic mixtures and tested as acetylcholinesterase (AChE) inhibitors. The conjunctive pharmacomodulation of huperzine A (carbobicyclic substructure) and tacrine (4-aminoquinoline substructure) led to compound 7jy, 2.5 times less active than tacrine as AChE inhibitor, but much more active than its (Z)-stereoisomer (7iy). Derivatives 7dy and 7ey, lacking the ethylidene substituent, showed to be more active than tacrine. Many other structural modifications of 7jy led to less active compounds. Compounds 7dy and 7ey also showed to be much more active than tacrine in reversing the partial neuromuscular blockade induced by d-tubocurarine.

Acetylcholinesterase↗

Developmental follow-up of 6-7 year old children of mothers employed during their infancies.

This study followed up 92 children at ages 6-7 first studied as one-year-olds in order to determine differences in the developmental outcome of the offspring of employed as compared to "stay at home" mothers. The developmental domain evaluated in the 6-7 year old children was peer competence, rated by laboratory play and child psychological test instruments. Mothers' reports of children's behavioral pathology at age 6-7 correlated with a higher number of maternal work hours during the infant's first year, but the children did better during overall play situations. Age 1 attachment ratings better predicted free play social competence for the entire sample than did maternal hours of work absence, but girls accounted for statistical significance. Maternal sensitivity from infancy was associated with maternal reports of (low) problem behaviors; however, regression analyses did not support the hypothesis that relations between either work status or attachment and current problem behaviors were mediated by early maternal sensitivity.

Child Care↗

Involvement of the L-arginine/nitric oxide neural pathway in non-adrenergic, non-cholinergic relaxation of the bovine oesophageal groove.

1. The distribution and localization of nitric oxide synthase (NOS) immunoreactivity and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) activity in the bovine oesophageal groove were investigated by immnunohistochemical and histochemical staining techniques. Functional in vitro studies were performed to correlate the presence of NOS-immunoreactivity (IR) and NADPH-d staining with smooth muscle relaxations involving the L-arginine/nitric oxide neural pathway in the bovine oesophageal groove activity. 2. NOS-IR and NADPH-d were expressed in nerve cell bodies of the myenteric, submucosal and intramuscular ganglia, and in nerve fibres distributed around blood vessels and throughout the different muscular layers of the bovine oesophageal groove. 3. In oesophageal groove strips treated with guanethidine (10(-5) M) and atropine (10(-7) M) to block noradrenergic neurotransmission and muscarinic receptors, respectively, electrical field stimulation (EFS, 0.5-32 Hz, 1 ms duration, 20-s trains) induced relaxations which were practically abolished by tetrodotoxin (TTX, 10(-6) M). 4. Incubation with an inhibitor of nitric oxide synthesis, NG-nitro-L-arginine (L-NOARG, 3 x 10(-5) M), significantly inhibited relaxations induced by EFS. This inhibition was partially reversed by L-arginine (L-arg, 5 x 10(-3) M). D-NOARG (3 x 10(-5) M) had no effect on EFS-induced relaxations. 5. NO added as an acidified solution of NaNO2 (10(-6) - 10(-3) M) and S-nitroso-L-cysteine (10(-7) - 10(-4) M) caused concentration-dependent relaxations of the bovine oesophageal groove. These relaxations were unaffected by L-NOARG (3 x 10(-5) M). 6. The presence of NO-synthesizing enzyme in nerves and ganglia, and the pharmacological evidence for NO-mediated smooth muscle relaxation suggested that the L-arg/NO neuronal pathway is involved in the inhibitory neurotransmission of the bovine oesophageal groove.

Animals↗

Single dose study of the bioequivalence of two sustained-release theophylline formulations.

The relative bioavailability of theophylline (CAS 58-55-9) was evaluated after a single dose administration of two sustained-release theophylline tablet formulations: Controfilina-200 as test preparation (test) and a commonly used reference preparation (reference). The design of the study was crossover in twelve healthy volunteers, with a series of two experimental sessions. The two sessions were carried out at weekly intervals. Theophylline concentrations were measured by HPLC (high performance liquid chromatography). The bioavailability was compared using the parameters: AUC0-infinity (area under the concentration-time curve), Cmax (maximal theophylline concentration), tmax (time after drug intake at which the maximal concentration is reached) and Cmax/AUC0-infinity. The results of this study indicated that the new generic sustained-release tablet and the reference are bioequivalent when the same dosage is administered.

Adult↗

[Toxic shock syndrome by group A beta-hemolytic streptococcus. Study of clonal relationship between a case and its contacts].

Group A Streptococcal infections have increased in severity and frequency worldwide. We report a female patient that was admitted by Group A Streptococcal lethal toxic shock syndrome due to pharyngitis as the primary focus and without cutaneous involvement. Streptococcus pyogenes was isolated from blood cultures and case definition fulfilled standard recommendations. Epidemiological studies among family members showed, that two children (aged 5 and 12 years) harbored the same strain in their pharynxes as confirmed by arbitrarily primed PCR (AP-PCR) using primers ERIC and Pn-1. Control strains were included in the analysis. None of three health care workers involved in intubation and laryngoscopic procedures with the patient carried S pyogenes. AP-PCR appears to be a useful and rapid procedure to demonstrate clonal relatedness among S pyogenes strains.

Adult↗

Allergic reactions to anisakis simplex parasitizing seafood.

BACKGROUND: The ingestion of Anisakidae ssp larvae parasitized fish can cause anisakiasis. Allergic reactions after ingestion of safely cooked but parasitized fish have been reported. METHODS: Twenty-three patients who suffered allergic reactions after seafood ingestion, with negative skin tests were studied. Anisakis simplex sensitization was assessed by skin prick test and/or specific serum Immunoglobulin E (IgE). Total serum IgE and specific IgE against the implicated seafood and Ascaris lumbricoides were also determined. RESULTS: Manifestations of Anisakis simplex allergy were urticaria/angioedema (18/23) patients and anaphylaxis (5/23). Gastric symptoms were also observed (3/23). Sea fish and shellfish were implicated. Raw and cooked seafood ingestion caused reactions. Total serum IgE ranged from 13 to 7200 KU/L. Specific IgE to Anisakis simplex was positive (> 0.35 KU/L) in all patients, and skin tests were positive in 20. Serum-specific IgE and skin tests to the involved seafoods were negative in every patient. Serum-specific IgE to Ascaris lumbricoides was negative in 13 patients. No association between total IgE and the eosinophil count (r < 0.1) was observed, but there was some association between total IgE and specific IgE to Anisakis simplex (r = 0.58). CONCLUSION: Anisakis simplex sensitization is the cause of allergic reactions after seafood ingestion. It is important to pay attention to this new "food allergy" to diagnose correctly the etiology of adverse food reactions.

Adolescent↗

[Massive tumorous pulmonary embolism in hepatocarcinoma].

Tumoral pulmonary embolism is among the causes of acute dyspnea in patients with neoplasia. This phenomenon, different to thrombotic embolism, occurs frequently in patients with lung, gastrointestinal, liver, breast and uterus neoplasia. It is usually asymptomatic and usually constitutes an autopsy finding in these patients. More rarely it manifests as a cor pulmonale which evolves subacutely. Exceptionally large tumoral emboli spread from a primary tumoral mass, and obstruct main pulmonary arterial vessels, causing a clinical picture indistinguishable from massive pulmonary thromboembolism. We present case of massive tumoral pulmonary embolism by an hepatocarcinoma. In spite of an early thrombolytic treatment the patient died from acute pulmonary hypertension.

Autopsy↗