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Biomedical subjects

A Castro

Publications and source records attributed to A Castro.

At least 91 records · Page 5Linked to original sources
PubMed2000

[Microdeletion of Y chromosome in severe olygozoospemic infertile patient].

We are reporting a 37 year old male with severe oligozoospermia and a history of infertility for thirteen years and surgery for severe unilateral varicocele. The hormonal levels for FSH, LH and T, and karyotype were within the normal range. Multiplex PCR revealed the presence of a de novo microdeletion in the azoospermia factor (AZF) c region involving the deleted in azoospermia (DAZ) and basic protein Y-2 (BPY2) genes. These results suggest that severe oligozoospermia should be considered for the screening of microdeletions of Yq involving the AZFc region even in the presence of a varicocele.

Adult↗
PubMed1999

Development of immunoreactivity to neuropeptide Y in the brain of brown trout (Salmo trutta fario).

The development of neuropeptide Y-immunoreactive (NPY-ir) neurons in the brain of the brown trout, Salmo trutta fario, was studied by using the streptavidin-biotin immunohistochemical method. Almost all NPY-ir neurons found in the brain of adults already appeared in embryonic stages. The earliest NPY-ir neurons were observed in the laminar nucleus, the locus coeruleus, and the vagal region of 9-mm-long embryos. In the lateral area of the ventral telencephalon, habenula, hypothalamus, optic tectum, and saccus vasculosus, NPY-ir cells appeared shortly after (embryos 12-14 mm in length). The finding of NPY-ir cells in the saccus vasculosus and the vagal region expand the NPY-ir structures known in teleosts. Among the regions of the trout brain most richly innervated by NPY-ir fibers are the hypothalamus, the isthmus, and the complex of the nucleus of the solitary tract/area postrema, suggesting a correlation of NPY with visceral functions. Two patterns of development of NPY-ir populations were observed: Some populations showed a lifetime increase in cell number, whereas, in other populations, cell number was established early in development or even diminished in adulthood. These developmental patterns were compared with those found in other studies of teleosts and with those found in other vertebrates. J. Comp. Neurol. 414:13-32, 1999.

Animals↗
PubMed1999

Chlorophenylmethyl benzothiadiazine dioxides derivatives: potent human cytomegalovirus inhibitors.

Modifications of our previously reported lead compounds, acyclonucleosides derived from 2,1,3-benzothiadiazine dioxides, in the search for inhibitors of human cytomegalovirus (HCMV), lead us to identify the chlorophenylmethyl benzothiadiazine dioxides derivatives as potent HCMV inhibitors. The synthesis and antiviral data of this second-generation of benzothiadiazine dioxide compounds are reported.

Anti-Infective Agents↗
PubMed1999

A comparison of the bronchodilatory effect of 50 and 100 microg salbutamol via Turbuhaler and 100 microg salbutamol via pressurized metered dose inhaler in children with stable asthma.

AIM: The aim of the study was to compare the efficacy of single doses of salbutamol Turbuhaler (50 and 100 microg), salbutamol pressurized metered dose inhaler (pMDI) (100 microg) and placebo in children with stable chronic reversible airway obstruction. Primary efficacy variable (FEV1-av) was calculated as the area under the curve of forced expiratory volume in one second (FEV1) (AUC, 0-4 h) and divided by the observed time. DESIGN: The study was of a randomized, single-dose, crossover and double-blind design. Seven centres participated. FEV1 was measured pre-dose and at 15 min, 0.5, 1, 1.5, 2, 3 and 4 h post study dose. PATIENTS: Forty asthmatic children (9 girls) with a mean age of 9 years (range: 6-12), mean FEV1 of 1.6 l (range: 0.9-2.4) and a mean FEV1 in percentage of predicted normal value of 80% (range: 61-109) were randomized into the study. The mean reversibility 30 min after inhaling 2x100 microg salbutamol from pMDI was 20% (range: 9-45) or 15% (range: 8-27) in percentage of predicted normal value. RESULTS: The mean FEV1-av was 1.63 l for placebo, 1.71 l for 50 microg salbutamol Turbuhaler, 1.76 l for 100 microg salbutamol Turbuhaler and 1.76 for 100 microg salbutamol pMDI. Corresponding values for maximum FEV1 were 1.76, 1. 85, 1.87 and 1.87 l, respectively. There were no statistically significant differences between the active treatments in FEV1-av or maximum FEV1. All active treatments were significantly better than placebo. CONCLUSION: No significant differences in bronchodilating effect between 50, 100 microg salbutamol Turbuhaler and 100 microg salbutamol pMDI in children, aged 6-12 years, with stable asthma could be demonstrated. All active treatments were significantly better than placebo.

Albuterol↗
PubMed1999

Novel potential agents for human cytomegalovirus infection: synthesis and antiviral activity evaluation of benzothiadiazine dioxide acyclonucleosides.

The first acyclonucleosides based on the benzothiadiazine dioxide system were synthesized following the silylation procedure. Several acyclic moieties, including acetoxyethoxymethyl, benzyloxymethyl, and propargyloxymethyl groups, were introduced. Two synthetic strategies were designed to selectively obtain the N-1 or N-3 derivatives. Lipase-mediated deacylation was used for the deprotection of the acyclonucleosides. Some of the benzothiadiazine dioxide acyclonucleosides, in particular 16, proved active against human cytomegalovirus (CMV) at concentrations slightly higher than that found for ganciclovir [50% inhibitory concentration (IC50) = 3. 5-3.7 micrograms/mL, cytotoxicity (CC50) >/= 40 micrograms/mL, MCC = 20 micrograms/mL]. Additionally, compound 16 inhibited the replication of human immunodeficiency virus type 1 (HIV-1) and HIV-2 in CEM cells at concentrations that were 5-fold lower than its cytotoxic concentration.

Anti-HIV Agents↗
PubMed1999

Selective, tight-binding inhibitors of integrin alpha4beta1 that inhibit allergic airway responses.

Integrin alpha4beta1 mediates leukocyte recruitment, activation, mediator release, and apoptosis inhibition, and it plays a central role in inflammatory pathophysiology. High-affinity, selective inhibitors of alpha4beta1, based on the Leu-Asp-Val (LDV) sequence from the alternatively spliced connecting segment-1 (CS-1) peptide of cellular fibronectin, are described that employ a novel N-terminal peptide "cap" strategy. One inhibitor, BIO-1211, was approximately 10(6)-fold more potent than the starting peptide and exhibited tight-binding properties (koff = 1.4 x 10(-4) s-1, KD = 70 pM), a remarkable finding for a noncovalent, small-molecule inhibitor of a protein receptor. BIO-1211 was also 200-fold selective for the activated form of alpha4beta1, and it stimulated expression of ligand-induced epitopes on the integrin beta1 subunit, a property consistent with occupancy of the receptor's ligand-binding site. Pretreatment of allergic sheep with a 3-mg nebulized dose of BIO-1211 inhibited early and late airway responses following antigen challenge and prevented development of nonspecific airway hyperresponsiveness to carbachol. These results show that highly selective and potent small-molecule antagonists can be identified to integrins with primary specificity for peptide domains other than Arg-Gly-Asp (RGD); they confirm the generality of integrins as small molecule targets; and they validate alpha4beta1 as a therapeutic target for asthma.

Animals↗
PubMed1999

IL-4 selectively inhibits IL-2-triggered Stat5 activation, but not proliferation, in human T cells.

IL-2 activates several distinct signaling pathways that are important for T cell activation, proliferation, and differentiation into both Th1 and Th2 phenotypes. IL-4, the major cytokine that promotes differentiation of Th2 cells, has been shown to block signaling of the Th1-promoting cytokine IL-12. As IL-2 synergizes with IL-12 in promoting Th1 differentiation, the effects of IL-4 on IL-2 signal transduction were investigated. IL-4 suppressed activation of DNA binding and tyrosine phosphorylation of the transcription factor Stat5 by IL-2, and suppressed the expression of the IL-2-inducible genes CD25, CIS, the PGE2 receptor, and cytokine responsive (CR) genes CR1 and CR8. Activation of Stat5 by cytokines that share a common gamma receptor subunit, IL-2, IL-7, and IL-15, was suppressed by preculture in IL-4. Activation of the Jak1 and Jak3 kinases that are proximal to Stat5 in the IL-2-Jak-STAT signaling pathway was suppressed, and this correlated with inhibition of IL-2Rbeta subunit expression. In contrast to suppression of Stat5, proliferative responses to IL-2 were augmented in IL-4-cultured cells, and activation of proliferative pathways leading to activation of mitogen activated protein kinases, induction of expression of Myc, Fos, Pim-1, and cyclin D3, and decreased levels of the cyclin-dependent kinase inhibitor p27 were intact. These results identify molecular mechanisms underlying interactions between IL-4 and IL-2 in T cells and demonstrate that one mechanism of regulation of IL-2 activity is selective and differential modulation of signaling pathways.

Base Sequence↗
PubMed1999

Bacillus cereus prosthetic valve endocarditis.

Bacillus cereus is a ubiquitous organism that often contaminates microbiological cultures but rarely causes serious infections. Reports of B. cereus endocarditis are infrequent. Infection in patients with valvular heart disease is associated with significant mortality and morbidity. We describe a case of B. cereus endocarditis involving a mechanical mitral prosthesis that resolved after replacement of the prosthetic valve. We also review the previous cases reported in the literature.

Bacillaceae Infections↗
PubMed1999

Synthesis of new 3,4,5-trisubstituted isothiazoles as effective inhibitory agents of enteroviruses.

The synthesis and evaluation of 3,4,5-trisubstituted isothiazoles as antiviral agents led to the discovery of several compounds effective in vitro against enteroviruses polio 1 and ECHO 9. Structure-activity relationship studies revealed that a short thioalkyl chain in the 3-position and a methyl ester group in the 4-position are the structural components that, to a large extent, contribute to the positive biological profile in terms of both selectivity and low cytotoxicity. Under one-step growth conditions, methyl 3-methylthio-5-phenyl-4-isothiazolecarboxilate caused the greatest activity if added within 1 h after poliovirus adsorption. These data suggest interference with early events of viral replication.

Antiviral Agents↗
PubMed1999

Single shock endocavitary low energy intracardiac cardioversion of chronic atrial fibrillation.

BACKGROUND: Discomfort related to low-energy internal cardioversion (LEIC) represents a real problem in patients (pts) with atrial fibrillation (AF). The aim of our study was to verify if a single shock could restore sinus rhythm (SR) with a lower discomfort for the pt. METHODS: Thirty pts with chronic AF were randomized to receive a single 350 V shock (15 pts) or multiple shocks of increasing energy (15 pts). Three leads were positioned, respectively, in the coronary sinus and in the lateral right wall for shock delivery, and in the right ventricular apex for R wave synchronization. Truncated, biphasic shocks were used. In the first group a single 350 V shock was directly delivered and a second 400 V shock was given only if SR has not been restored. In the second group, beginning at 50 volts the voltage was increased in steps of 50 volts until SR restoration. No patient was sedated. After each shock the pts were asked to rate their discomfort on a scale of 1 to 5 (1 = not perceived, 5 = severe discomfort). RESULTS: SR was restored in all the subjects. In group 1 SR was obtained in 12/15 (80%) pts with the first 350 V (8.1 +/- 0.8 joules) shock, while the remaining 3 patients required the second 400 V (10.2 +/- 0.3 joules) shock. In group 2 the mean atrial defibrillation threshold was 346.7 +/- 1029.7 volts (8.0 +/- 101.5 joules). Then discomfort score was 2.5 +/- 0.6 in group 1 and 3.3 +/- 10.6 in group 2 (p < 0.01). CONCLUSIONS: A single shock of 350 V restores SR in the majority of pts with chronic AF; by use this new approach, LEIC is tolerated better than the multiple shocks step-up protocol.

Aged↗
PubMed1999

Long-term re-treatment with interferon and ribavirin combination therapy in patients with chronic hepatitis C who are non-responders to interferon alone: a preliminary study.

We evaluated the efficacy and tolerance of ribavirin and IFN-alpha combination therapy over 12 months in 28 patients who were non-responders to IFN-alpha alone. Of 24 patients who have finished the therapy, 6 (25%) obtained a complete response (normal ALT and negative HCV RNA) at the end of treatment and maintained a sustained response 27% (5/18).

Adult↗
PubMed1999

Use of hypertonic saline/acetate infusion in treatment of cerebral edema in patients with head trauma: experience at a single center.

BACKGROUND: Hypertonic saline (HS) recently has been introduced as a new form of hyperosmolar treatment in patients with brain injury from diverse causes. We reviewed our experience with the use of continuous hypertonic saline/acetate infusion in patients with cerebral edema attributable to head trauma. METHODS: We performed a retrospective chart review of all patients admitted with severe head injury, defined as admission Glasgow Coma Scale score of 8 or less, in the neurocritical care unit of a University hospital. Intravenous infusion of 2% or 3% saline/acetate for treatment of cerebral edema was introduced in the unit in April of 1993. The clinical characteristics, interventions required, and outcomes in patients who received HS were compared with patients who received 0.9% saline infusion only. Multivariate analyses were used to evaluate the impact of HS use on in-hospital mortality and Glasgow Outcome Scale score at discharge. RESULTS: Thirty-six patients with cerebral edema caused by head trauma received infusion of HS initiated within 48 hours of admission for a mean period of 72 +/- 85 hours. Compared with 46 patients who did not receive HS, there were no differences observed in age and admission Glasgow Coma Scale scores. Patients who received HS were more likely to have a penetrating injury (p = 0.07) and a mass lesion on initial computed tomographic scan (p = 0.07). There was no difference between frequency of use of hyperventilation, mannitol, cerebrospinal fluid drainage, and vasopressors between the two groups. The requirement for pentobarbital coma was higher in HS group (n = 7 patients) versus control group (n = 2,p = 0.04). After adjusting for differences between both groups, infusion of HS was associated with higher in-hospital mortality (OR, 3.1; 95% CI, 1.1-10.2). CONCLUSION: HS administration as prolonged infusion does not seem to favorably impact on requirement for other interventions and in-hospital mortality in our experience. Further efforts should be directed toward use of HS as bolus administrations or short infusions.

Adult↗
PubMed1999

Replacement for 30-milliliter flat-bottomed, glass-stoppered, round bottles used in VDRL antigen preparation.

When the flat-bottomed, glass-stoppered, round bottle traditionally used to make VDRL antigen was discontinued, an appropriate substitute was needed. Although many laboratories have switched to one of the other nontreponemal tests for syphilis serology screening, the VDRL test remains the only approved procedure for testing spinal fluids of patients with possible neurosyphilis. We tested 25-ml glass-stoppered, convex-bottomed Erlenmeyer flasks to determine if these could be used as appropriate substitutes. We tested 52 reactive sera and 54 nonreactive sera by using one reference antigen prepared in the traditional flat-bottomed bottles and five antigens prepared in the Erlenmeyer flasks. Results with all serum samples were comparable. We also tested two lots of a commercial antigen plus an additional lot of reference antigen. Again there was no difference in the reactivity of the antigens. Therefore, we conclude that 25-ml glass-stoppered Erlenmeyer flasks can be used as an appropriate substitute for glass-stoppered, flat-bottomed, round glass bottles in the making of VDRL antigen.

Cardiolipins↗
PubMed1999

Interleukin-1beta (IL-1beta) is a modulator of human luteal cell steroidogenesis: localization of the IL type I system in the corpus luteum.

The present investigation examined the effect of interleukin-1beta (IL-1beta) on progesterone production by human luteal cells and the expression and localization of the IL-1 system in the human corpus luteum (CL). Luteal cells were isolated from corpora lutea collected throughout the luteal phase. After dispersion, luteal cells were treated with a panel of monoclonal antibodies directed to leukocyte-specific molecules. The leukocytes were isolated with immunomagnetic beads. Leukocyte-free luteal cells exhibited greater steroidogenic responsiveness to hCG toward the end of the luteal phase. The treatment of mixed luteal cells (total luteal cells) with IL-1beta inhibited by 60% hCG-stimulated progesterone production. Interestingly, the treatment of leukocyte-free luteal cells with IL-1beta did not affect progesterone production. In addition, the treatment of mixed luteal cells with monoclonal antibodies against IL-1 receptor type I (IL-1RtI) resulted in a 2.5-fold increase in the hCG-supported progesterone production. IL-1RtI and IL-1 receptor antagonist were localized by immunohistochemistry in both somatic and immune cells of the CL. Flow cytometric analysis indicated that both nonleukocyte luteal cells and leukocyte-luteal cells exhibited IL-1Rt-I positive cells, representing 56% and 31% of the total luteal cells, respectively. However, 13% of nonleukocyte luteal cells did not express IL-1Rt-I. Northern analysis demonstrated the presence of the 5.1-kb IL-1RtI messenger ribonucleic acid transcript in CL of different ages. RT-PCR indicated that both leukocyte-free luteal cells and luteal leukocytes express IL-1RtI messenger ribonucleic acid. We conclude that 1) luteal leukocytes have an inhibitory effect on hCG-stimulated progesterone production; 2) IL-1beta inhibits hCG-stimulated progesterone production only in mixed luteal cell cultures, indicating that leukocytes mediate the effect; 3) the somatic and immune cells of the CL are sites of action and expression of the IL-1 system; and 4) interaction between the steroidogenic and immune cells of the CL suggests a functional intraovarian role for IL-1beta in CL physiology.

Adult↗
PubMed1999

Spatial extension of local pacing capture in the lateral free wall of the right atrium during clinical chronic atrial fibrillation.

OBJECTIVES: The aims of our study were to define the spatial extension of local atrial pacing capture (LAPC) in the right lateral atrial wall and to verify the effects of antiarrhythmic drugs on capture extension. BACKGROUND: Recently, LAPC during spontaneous chronic atrial fibrillation (AF) has been demonstrated directly in humans, but no systematic attempt has been made to evaluate its spatial extension. METHODS: The study was conducted in 14 consecutive patients with chronic AF, nine of whom were taking antiarrhythmic drugs. A Franz catheter for pacing and monophasic action potential recording was positioned in the lateral right atrial wall. An octopolar recording lead was positioned about 10 mm apart. The presence of atrial capture and its extension (number of captured bipolar pairs) were evaluated during decremental pacing. RESULTS: Forty-eight atrial capture attempts were made. LAPC was achieved in all the performed attempts. The AF types immediately before capture were type 1 in 35 (73%) and type 2 in 13 (27%) episodes. In 32 episodes, the capture was lost within 15 seconds and in the remaining 16 pacing was stopped after 15 seconds of stable capture. In 26 episodes, capture extended radially up to 4 cm from the pacing site, in 18 up to 3 cm, in 3 up 1 cm and in 1 up 1 cm. The mean extension in patients being treated with antiarrhythmic drugs was significantly greater than what was seen in untreated patients (3.8 +/- 0.4 vs 2.9 +/- 0.7 cm, p < 0.00001). Capture loss was less frequently observed when all four of the bipolar recording sites had been captured (13/25, 52% vs 19/23, 82%, respectively, p = 0.05). CONCLUSIONS: LAPC in the lateral right atrial wall extends over a radius of 30-40 mm in the majority of capture episodes and is greater in patients treated with antiarrhythmic drugs. Our results suggest that, at least theoretically, simultaneous multisite pacing could be used to terminate AF. Moreover, a reduction in the atrial defibrillation threshold could be expected performing low-energy internal cardioversion during LPC.

Aged↗