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Biomedical subjects

F Rodriguez

Publications and source records attributed to F Rodriguez.

At least 19 recordsLinked to original sources

Synthesis and evaluation of trimetoquinol derivatives: novel thromboxane A2/prostaglandin H2 antagonists with diminished beta-adrenergic agonist activity.

Trimetoquinol (TMQ, 1) is a unique catecholamine with a strong stereodependence for agonism at beta-adrenergic (S > > R) and antagonism at thromboxane A2/prostaglandin H2 (TP; R > > S) receptors. Our laboratory has reported the effects of N-alkylation and modification of the trisubstituted benzyl group in these receptor systems. For iodinated derivative 5, maintaining potency in TP receptor systems (112%) was coupled with maintaining limited potency in beta-adrenergic receptor systems (34% for beta 1 and 47% for beta 2). In this study, several diverse TMQ derivatives were prepared to probe for binding interactions specific to a particular receptor system. Planar amidine 2, which was designed to explore the importance of TMQ's chiral center, showed a dramatic loss of potency (< 1%) in each receptor system. Likewise, the homologation of a previously described N-benzyl derivative (3) to the N-phenylethyl derivative 4 also showed reduced potency (< 3%) in both receptor systems. However, modification of the trimethoxybenzyl group of TMQ to a 4-hydroxy-3-nitrobenzyl group (7) provided a unique lead for TMQ derivatives with significant potency in TP receptor systems (91%) and reduced potency in beta-adrenergic receptor systems (4% for beta 1 and 19% for beta 2).

Adrenergic beta-Agonists

Use of buccal fat pad to repair intraoral defects: review of 30 cases.

The buccal fat pad has been frequently used for the closure of oro-antral and oro-nasal communications. There are a few studies in the literature reporting its use in defects secondary to tumoral resections. In this paper we consider both the anatomical basis and the surgical technique. We also review 30 cases, used for the repair of 15 defects due to tumoral resections, 8 to maxillary cysts, 6 to communications and 1 secondary to a postraumatic defect. It has been successful in 28 of the 29 patients, with a complete epithelization of the flap, even in 4 cases with partial necrosis of the pad. It is an acceptable type of reconstruction, versatile and of a simple surgical technique. However, its use is limited to small or medium defects, being sometimes scarce.

Adenoma, Pleomorphic

Tectal codification of eye movements in goldfish studied by electrical microstimulation. f.

This work compares the tectal codification of eye movements in goldfish with those reported for other vertebrate groups. Focal electrical stimulation was applied in various tectal zones and the characteristics of evoked eye movements were examined as a function of (i) the position of the stimulation over the tectal surface, (ii) the initial position of the eyes and (iii) the parameters (pulse rate, current strength, duration) of the stimulus. In a large medial zone, stimulation within the intermediate and deep layers of the tectum evoked contraversive saccades of both eyes, whose direction and amplitude were roughly congruent with the retinotopic representation of the visual world within overlying layers. These saccades were minimally influenced by the initial position of the eye in the orbit. The topographical arrangement of evoked saccades and body movements suggests that this tectal zone triggers orienting responses in a similar way to those described in other vertebrates. Stimulations applied within the caudal tectum also evoked contraversive saccades, but in disagreement with the overlying retinotopic map--the vertical component was absent. Taken together with electrically evoked body movements reported in free-swimming fish, these saccades could reveal that this zone is involved in escape responses. When stimulations were applied within the anteromedial zone of the tectum, contraversive movements of both eyes appeared much more dependent on initial eye position. Saccades elicited from this area displayed characteristics of "goal-directed saccades" which were similar to those described in the cat. The generation of goal-directed movements from the anteromedial zone suggests that this portion of the goldfish optic tectum has a different intrinsic organization or is connected with the brainstem saccade generator in a different fashion than the medial zone. Finally, stimulation of the extreme anteromedial zone evoked convergent eye movements. These movements and those reported in free-swimming fish following electrical stimulation of this tectal area suggest that this zone could be involved in feeding responses. The relationships between the parameters of electrical stimulation and the characteristics of elicited saccades suggest that the stimulated location within the tectum determines a constant direction in the evoked saccade, whereas the amount and duration of tectal activity, as mimicked by changes in stimulus parameters, together with the tectal locus, determine the velocity and amplitude of the evoked saccade.

Animals

Early detection of sequela-prone osteomyelitis in children with use of simple clinical and laboratory criteria.

To determine which clinical or laboratory criteria best reflected the prognosis for 83 children with acute hematogenous osteomyelitis (AHO), they were compared with outcomes after a follow-up of at least 2 months (for 78%, > or = 6 months). Twenty-eight children (34%) developed sequelae. They had higher serum C-reactive protein (CRP) concentrations (days 1-6 of treatment; P = .0004 to .0001) and higher clinical scores (P = .0001) than did patients who had an uneventful recovery. The frequency of sequelae increased from 3% to 73% (P = .0001) when CRP concentrations exceeded the defined cutoff limits and the clinical scores were > or = 1. Age, the duration of symptoms at diagnosis, and the type and duration of intravenous antimicrobial therapy or surgical management did not differ (P > .05) between children with and without sequelae. Both CRP determinations and clinical evaluations with use of a scoring system enable early detection of sequela-prone AHO in children and are most accurate when used together.

Adolescent

Linkage mapping of a large Colombian family segregating for X linked retinoschisis: refinement of the chromosomal location.

Juvenile X linked retinoschisis (RS) is a bilateral vitreoretinal dystrophy that develops early in life. Previous linkage studies have localised the RS gene to Xp22.1-p22.3 between DXS207 and AFM 291Wf5, which represents a genetic distance of approximately 3.7 cM. In an effort to facilitate the eventual cloning of the RS gene, we have analysed a large Colombian family, using 10 microsatellite markers that have been mapped to the region Xp22.1-p22.3. A total of 93 members, including 19 affected and eight unaffected males, two affected females, and six obligate carrier females were analysed. Close linkage was observed between the disease locus and DXS999 (Zmax = 2.27, theta max = 0.05), DXS987 (Zmax = 2.61, theta max = 0.1), DXS443 (Zmax = 4.23, theta max = 0.1), and DXS274 (Zmax = 3.49, theta max = 0.05) markers. Recombination with the RS locus was found for all marker loci except DXS197, DXS43, and DXS1195. These results place the RS locus within an interval of approximately 2 cM between the flanking markers DXS1053 and DXS999, approximately 1.7 cM closer than the previously reported boundary. The results also further confirm the lack of genetic heterogeneity of RS.

Alleles

Comparative trial of 3 days of azithromycin versus 10 days of clarithromycin in the treatment of children with acute otitis media with effusion.

The authors compared the efficacy, safety and tolerance of azithromycin and clarithromycin in pediatric patients with acute otitis media. A randomized, open clinical trial was performed comparing azithromycin and clarithromycin in children aged 6 months to 12 years of age with acute otitis media with effusion. Patients were allocated to azithromycin at 10 mg/kg once daily for 3 days or to clarithromycin at 15 mg/kg day divided into two equal doses for 10 days. Clinical examinations and tympanometric evaluations were performed at baseline, day 3-5, day 10-14, day 28-30 and day 50-60. Tympanocentesis fluid cultures were collected at enrollment and urine and blood samples were obtained at baseline and day 10-14. Of 100 patients enrolled, 97 were considered evaluable. The most common middle ear pathogens were Streptococcus pneumoniae (60%), Haemophilus influenzae (15%) and Staphylococcus aureus (13%). Fifty patients (100%) treated with azithromycin and 45 (95.7%) patients treated with clarithromycin had a satisfactory clinical response. Rates of persistence of middle ear effusion and possible drug related side effects were comparable. Based on the efficacy and safety results, azithromycin for 3 days and clarithromycin for 10 days are considered to represent an attractive alternative for the treatment of children with acute otitis media.

Anti-Bacterial Agents

Chronic delta hepatitis: is the prognosis worse when associated with hepatitis C virus and human immunodeficiency virus infections?

Eighty-six patients were followed for 6.5 years to study the epidemiological, virological, and histological course of chronic delta hepatitis and the relationship of this disease with HIV and HCV infection. Patients were classified into four groups according to simultaneous HCV and/or HIV infection: group 1, HDV infection (20 cases); group 2, HDV and HCV infection (11 cases); group 3, HDV and HIV infection (12 cases), and group 4, HDV, HCV, and HIV infection (43 cases). All but 14 patients were asymptomatic at presentation. Liver histology showed chronic active hepatitis in 53 cases and cirrhosis in 19 cases. During followup, 52 patients remained asymptomatic, 34 developed hepatic dysfunction, 28 died, and 1 received a liver transplant. Among the 28 patients who died, 4 had HDV infection; 3 HDV and HCV infection; 3 HDV and HIV infection; and 18 HDV, HCV, and HIV infection. Death was due to liver failure in 16 (57%), AIDS in 10 (36%), and was unrelated to liver disease in 2 (8%) cases. There results demonstrate that chronic delta hepatitis is a severe disease, especially among drug users with HIV and HCV infection. The high morbidity and mortality of chronic delta hepatitis justifies the use of antiviral therapy to modify the natural course of the disease.

Adolescent

PAH content and mutagenicity of marine sediments from the Venice lagoon.

Sediments from the Venice lagoon, a polluted coastal environment in northeastern Italy, were assayed for mutagenicity and content of several toxic microcontaminants, which included selected polycyclic aromatic hydrocarbons (PAHs); the latter are specifically dealt with in this paper. Samples were collected at three lagoon sites with reasonably distinct environmental features--urban, industrial, or agricultural--and at two others considered to be under mixed pollution influences; a sixth sample was obtained from an open sea area to act as background control. The organic matter (EOM) associated with the mineral substrata was extracted; after cleanup, analyte determination was carried out by HRGC-LRMS(SIM) using isotopically labeled compounds as internal standards. Cumulative levels of the selected PAHs were found to be in the range of 0.065 to 0.46 micrograms/g of dry matrix at five sites; a much higher concentration (48 micrograms/g) was detected in the sample from the urban environment. The remarkable PAH level increase at this site was mostly accounted for by the concurrent, apparent increase of EOM contamination as PAH concentration was seen to reach 32 micrograms/mg of EOM from < 1 microgram/mg at the five remaining sites. Mutagenicity assays with Salmonella typhimurium strains TA98 and TA100 of marine sediment organic extracts also highlighted a distinct activity in the sample from the urban site. Further fractionation and analysis of this extract pointed to PAHs as the main mutagenic component present in the sediment matrix, possibly accounting for up to approximately 70-80% of the entire mutagenic potential detected.

Environmental Exposure

The structural protein p54 is essential for African swine fever virus viability.

Protein p54, one of the most antigenic structural African swine fever virus (ASFV) proteins, has been localized by immuno-electron microscopy in the replication factories of infected cells, mainly associated with membranes and immature virus particles. Attempts to inactivate the p54 gene from ASFV by targeted insertion of beta-galactosidase selection marker was uniformly unsuccessful, suggesting that this gene is essential for virus viability. To demonstrate that, we inserted in the TK (thymidine kinase) locus of the virus a construction containing a second copy of the p54 gene and beta-glucuronidase selection marker under the control of p54 and p73 promoters, respectively. Virus mutant clones expressing a second copy of p54 and beta-glucuronidase were used to achieve deletion mutants of the original copy of the gene. Virus mutants expressing only the second inserted copy of p54 and the two selection markers mentioned above were successfully obtained. Therefore, we have demonstrated that the p54 gene product plays an essential role in virus growth, characterizing for the first time in ASFV an essential virus gene.

African Swine Fever Virus

Detection of Mycoplasma mycoides subspecies mycoides by monoclonal antibody-based sandwich ELISA.

Monoclonal antibodies (MAbs) were produced from a mouse immunised with Mycoplasma mycoides subsp. mycoides small colony (MmmSC) antigen and their use to detect and differentiate strains within the Mycoplasma mycoides cluster investigated in an antigen capture ELISA format. The MAbs produced could not distinguish between MmmSC and M. mycoides subsp. mycoides large colony (MmmLC) strains. However, the sandwich ELISAs developed were able to specifically distinguish these two biotypes from the other four members of the M. mycoides cluster, and from all other mycoplasma or bacteria species examined. The most sensitive application of the test was a combination of enrichment and capture by overnight or 48-h incubations of samples inoculated into mycoplasma broth in antibody-coated microtiter wells.

Animals

Radiofrequency as a lesioning model in experimental spinal cord injury.

Many models have been developed to study spinal cord injury (SCI), such as cryogenic lesioning, hot water injury, scalpel lesioning, compressive trauma using clips, electromechanical devices, extradural cuffs, and weight-drop techniques. In this study, the radiofrequency (RF) lesion was used for inducing an experimental SCI in cats. The neuropathology was correlated with the MRI. In this model, 4 cats were injured at the thoracic spinal cord (T11-T12) with a lesion of 65 degrees C for 1 min using a micromanipulated penetrating RF electrode. The MRI of the lesions after 2, 3, 5, and 6 weeks post-injury as well as the correlative histological changes were obtained. The RF-induced lesion was discrete with little spreading across the spinal cord. There was a good correlation between the histopathology findings and the MRI. We conclude that experimental RF lesioning of the spinal cord can produce a consistent lesion with predictable histopathological changes in experimental animals. A 65 degree C injury for 1 min induced a clinical picture of an incomplete SCI. The RF lesioning should be considered as a new model to study SCI, particularly those with a penetrating component.

Animals

Collagen dysplasia in a litter of Garafiano shepherd dogs.

A connective tissue disease resembling the human Ehlers-Danlos syndrome is reported in three Garafiano shepherd dogs from the same litter. The clinical signs included skin hyperextensibility and fragility, joint laxity, and ocular lesions. Microscopical studies showed abnormalities in the packing of collagen in fibrils and fibres in the skin. Systemic connective tissue defects were demonstrated in one necropsied puppy.

Animals

An immunohistochemical method of detecting Mycoplasma species antigens by use of monoclonal antibodies on paraffin sections of pneumonic bovine and caprine lungs.

Lung samples from pneumonic lesions in cattle and goats, naturally or experimentally infected with strains of the Mycoplasma mycoides cluster, were fixed in formalin and embedded in paraffin. An immunohistochemical technique using monoclonal or polyclonal antibodies was performed on tissue sections in order to detect Mycoplasma antigens. Four monoclonal antibodies (MAbs), one (2A3) raised against M. mycoides ssp. mycoides small colony (SC) and large colony (LC), two (1D3 and 5E5) against M. mycoides ssp. capri, and one (5A10) against M. bovis, were used. A range of polyclonal antibodies, raised to the individual subspecies of the M. mycoides cluster, and one to Pasteurella haemolytica, was also used. The MAb 2A3 showed positive immunostaining in lung sections from cattle and goats naturally and experimentally infected with M. mycoides ssp. mycoides SC and LC, but not with pneumonic lesions of cattle and goats due to other members of the M. mycoides cluster, M. bovis or Pasteurella spp. The MAb 1D3 showed immunostaining in lung sections from goats naturally and experimentally infected with M. mycoides ssp. capri, but again not with pneumonic lesions caused by other members of the M. mycoides cluster, M. bovis or Pasteurella spp. The MAb 5E5 immunoreacted in sections from pneumonic lesions from all animals infected with one of the three M. mycoides cluster subspecies used in the study, but not with M. bovis or Pasteurella infected tissue. Immunoreaction was mainly found in the cell debris around necrotic areas, as well as in macrophages, neutrophils and epithelial cells. The localization of antigens of the M. mycoides cluster using polyclonal antisera followed basically the same pattern as that obtained with the monoclonals. However, a wide cross reactivity was found between different antisera and relatively high background immunostaining was also seen, especially in necrotic areas. The results suggest that immunohistochemical methods using monoclonal antibodies are useful tools for the diagnosis and study of the pathogenesis of pneumonia caused by the Mycoplasmas of the M. mycoides cluster.

Animals

Nephroprotective effect of cilastatin in allogeneic bone marrow transplantation. Results from a retrospective analysis.

Cilastatin, an inhibitor of the tubular brush border enzyme dehydropeptidase-I, is added in a fixed combination to imipenem. Cilastatin has been demonstrated in different animal models and in one clinical trial, to reduce the nephrotoxicity associated with cyclosporin A. To evaluate a possible nephroprotective effect of cilastatin following allogeneic BMT we conducted a retrospective analysis of 104 patients transplanted in our BMT Unit from January 1991 to January 1995. Imipenem/cilastatin (I/C) was used in a non-randomized manner in 64 patients during this period. Acute renal failure (ARF) was diagnosed in 32 patients (30%). ARF was not associated with gender, sepsis, conditioning regimen, underlying disease, bilirubin, or age. VOD occurred in 12/32 (37.5%) of patients with ARF whereas it occurred in only 7/72 (9.7%) of patients without ARF (P < 0.0007). ARF was not correlated with use of aminoglycosides, vancomycin, ciprofloxacine, ceftazidime or amphotericin-B. However, 13 patients of 64 exposed to I/C (20.3%) developed ARF vs 19 of 40 patients (47.5%) who were not exposed to I/C (P < 0.003; OR 0.28). Stratified analysis and multiple logistic regression confirmed the I/C nephroprotective action. The mean cyclosporin A levels in the I/C group were significantly decreased (208.6 +/- 64.9) vs the non-I/C group (265 +/- 118). We conclude that these results suggest I/C may counteract acute cyclosporin A nephrotoxicity following BMT and further prospective clinical trials are needed to confirm if routine administration of cilastatine confers benefit in the BMT setting.

Acute Kidney Injury

Highly specific confirmatory western blot test for African swine fever virus antibody detection using the recombinant virus protein p54.

A Western blot technique using a recombinant protein has been developed to confirm positive results obtained in African swine fever (ASF)-specific antibody detection by ELISA. The new confirmatory Western blot is based on the use of protein p54, one of the most antigenic ASF virus structural proteins, expressed in Escherichia coli fused to the N-terminus of MS2 polymerase. The recombinant Western blot assay was highly specific and equally sensitive for ASF virus-infected pigs detection as the conventional Western blot, which uses virus-induced proteins ranging in molecular weight between 23 and 35 kDa. The novel Western blot assay provides a simpler interpretation of the test, eliminates the possibility of false-positive reactions produced by cellular compounds that contaminate the antigen employed in the conventional technique, and avoids the use of live virus in antigen production.

African Swine Fever