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Biomedical subjects

M Soria

Publications and source records attributed to M Soria.

44 records · Page 3Linked to original sources

Immunotoxins, ligand-toxin conjugates and molecular targeting.

Biotechnology provides tools for therapeutic exploitation following advances in the elucidation of protein-to-cell and cell-to-cell interactions. Molecular targeting of bacterial and plant toxins to the desired district of action can be achieved through effector molecules like monoclonal antibodies or protein ligands. Biochemical conjugation of these effectors to SO-6, a single-chain Ribosome Inactivating Protein from Saponaria officinalis, yielded powerful cytotoxic agents that are attractive candidates for therapeutic evaluation. Cloning of the gene for this plant toxin has been achieved. Technologies for expression of protein ligands, such as apolipoproteins or several growth factors, are available in recombinant microorganisms, providing adequate partners for the assembly of targeted chimaeras. Domain engineering of structural and functional regions in effector proteins is now possible and will be carried out with the available technologies to improve existing therapy.

Biotechnology↗

Development and characterization of pituitary GH3 cell clones stably transfected with a human proinsulin cDNA.

Successful beta-cell replacement therapy in insulin-dependent (type I) diabetes is hindered by the scarcity of human donor tissue and by the recurrence of autoimmune destruction of transplanted beta cells. Availability of non-beta cells, capable of releasing insulin and escaping autoimmune recognition, would therefore be important for diabetes cell therapy. We developed rat pituitary GH3 cells stably transfected with a furin-cleavable human proinsulin cDNA linked to the rat PRL promoter. Two clones (InsGH3/clone 1 and 7) were characterized in vitro with regard to basal and stimulated insulin release and proinsulin transgene expression. Mature insulin secretion was obtained in both clones, accounting for about 40% of total released (pro)insulin-like products. Immunocytochemistry of InsGH3 cells showed a cytoplasmic granular insulin staining that colocalized with secretogranin II (SGII) immunoreactivity. InsGH3 cells/clone 7 contained and released in vitro significantly more insulin than clone 1. Secretagogue-stimulated insulin secretion was observed in both InsGH3 clones either under static or dynamic conditions, indicating that insulin was targeted also to the regulated secretory pathway. Proinsulin mRNA levels were elevated in InsGH3 cells, being significantly higher than in betaTC3 cells. Moreover, proinsulin gene expression increased in response to various stimuli, thereby showing the regulation of the transfected gene at the transcriptional level. In conclusion, these data point to InsGH3 cells as a potential beta-cell surrogate even though additional engineering is required to instruct them to release insulin in response to physiologic stimulations.

Animals↗

[Multicenter study on nosocomial candidiasis in the Republic of Argentina].

A multicenter study was performed between April and September 1998 with the participation of 12 medical centers located in 8 different provinces and in the capital city of Argentina. The aim of this study was to determine the species distribution and the antifungal susceptibility profile of isolates causing nosocomial fungal infections. All the fungal isolates obtained were sent to the Mycology Department for reference identification and antifungal susceptibility testing. Eighty-nine isolates were received from different clinical specimens. The distribution of species obtained was C. albicans (50.6%), C. tropicalis (22.5%), C. parapsilosis (20.2%), C. krusei (3.4%), C. glabrata (2.2%) and Debaryomyces hansenii (1.1%). Most of the isolates (85/88) had MICs for amphotericin B < or = 1 microgram/ml, C. krusei showed resistance to fluconazole but was dose dependent susceptible to itraconazole, C. glabrata (2/2) were resistant against both drugs, most of the isolates of C. albicans, C. tropicalis and C. parapsilosis were susceptible to these triazole drugs. These data showed a different distribution of Candida species compared with results obtained in other countries. The low frequency of appearance of C. krusei and C. glabrata in our country suggests a reduced selective pressure by triazoles.

Antifungal Agents↗

[Malassezia species isolated from skin diseases in a care center in the city of Buenos Aires, Argentina].

The epidemiology of Malassezia genus is poorly understood; geographical and population factors might have influence on the species distribution. The aim of this work was to determine the frequency of Malassezia species involved in skin diseases in a diagnostic center at Buenos Aires City. From 02/01/1999 to 10/31/2001, 456 skin specimens from 447 patients diagnosed as pityriasis versicolor, seborrheic dermatitis, foliculitis and atopic dermatitis, were analyzed by microscopic examination and culture. Malassezia spp was evidenced in 255 skin samples (55.9%) by microscopic analysis but it could be recovered from only 99 (38.8%) specimens. Malassezia species were isolated from 10 (3.9%) scarring lesions that were negative by microscopy. Among 109 isolates, M. sympodialis (58.7%) was the most frequent, followed by M. globosa and M. furfur (18.3% and 9.2%). Unique isolates (0.9%) of M. obtusa, M. slooffiae and M. restricta were recovered. Eleven isolates (10.1%) could not be identified because they had lost viability in the culture. This is the first study on Malassezia species associated to skin diseases in Argentina; further screening including other geographic regions of the country is necessary in order to confirm these results.

Adolescent↗

[Immunodiagnosis of endemic mycoses and bronchopulmonary aspergillosis: a multicenter study in Argentina].

In order to contribute to the knowledge of the relative frequency of chronic fungal diseases and assess the performance of diagnostic laboratories in Argentina, a multicenter study was performed with the participation of 25 medical centers located in 12 different provinces and Buenos Aires City. Between 04-01-2000 and 03-30-2001, 965 serum specimens from patients clinically suspected of having histoplasmosis (HP), paracoccidioidomycosis (PCM), coccidioidomycosis (CM) or aspergilosis were analyzed. Agar immunodiffusion tests (IDD) were done locally. All positive and 35% of negative sera were retested in the reference center. Results of laboratories of origin showed 98.8% concordance with those of reference center. Antibodies against any of the etiological agents were detected in 120 specimens from 98 patients. Endemic mycoses (HP, PCM and CM) were diagnosed in 70 patients (71.4%) and aspergilosis in 28 (28.6%). The frequencies of the different mycoses in decreasing order were PCM 47 patients (47.9%), aspergilosis 28 patients (28.6%), HP 13 patients (13.3%) and CM 10 patients (10.2%). The study was carried out on a voluntary basis and some areas of the country were not represented. However, the frequencies were in range with the expected rates in the population under study.

Argentina↗

[Multicenter study of fungemia due to yeasts in Argentina].

The incidence of candidemia has increased approximately 500% in high-complexity hospitals. A change in the spectrum of Candida infections due to species other than Candida albicans has also been detected. Between April 1999 and April 2000 a multicenter study was performed in order to determine the species distribution associated to candidemias in Argentina and the susceptibility profile of the isolates to the current antifungal drugs. Thirty six institutions have participated. All the 265 yeast strains isolated from blood cultures were identified by morphological, physiological, and biochemical tests. The antifungal susceptibility testing of isolates was performed based on the reference NCCLS procedure. The distribution of species was: Candida albicans (40.75%), Candida parapsilosis (28.67%), Candida tropicalis (15.84%), Candida famata (3.77%), Cryptococcus neoformans (3.77%), Candida glabrata (2.64%), and others (4.53%). Most of the isolates were susceptible to amphotericin B, fluconazole and itraconazole. Mortality associated to the fungemia by yeasts episodes (n=265) was 30%, lower than results previously determined (33-54%). The mortality percentage in patients who received antifungal therapy versus patients without treatment was 26.3% and 47%, respectively.

Amphotericin B↗

Prospective assessment of the role of antibiotic prophylaxis in ERCP.

BACKGROUND/AIMS: Despite the existence of published recommendations, various studies of antibiotic prophylaxis have reached conflicting conclusions, and controversy exists regarding the role of antibiotic prophylaxis in ERCP. The aim of this study was to analyze the efficacy of the intramuscular administration of clindamicine and gentamicine before ERCP. METHODOLOGY: Sixty-one consecutive patients referred for ERCP were prospectively randomized to receive either clindamicine 600mg and gentamicine 80mg, both intramuscularly one hour before the ERCP (group I; 31 patients) or not (group II; 30 patients). Two blood samples were obtained from every patient (just before endoscopy and within 5 minutes of withdrawal of the endoscope) and were incubated for 7 days and examined daily for growth of bacteria. Patients were closely monitored for 7 days after endoscopy to detect the development of infectious complications. RESULTS: Only 7 cultures from 7 patients were positive. Four were obtained post-ERCP (two patients in group I and two in group II) and the remaining three before endoscopy. The post-ERCP isolated bacteria were: Streptococcus mitis, Peptoestreptococcus anaerobious, Moraxella spp and Escherichia coli. Two patients, one from each group, developed post-ERCP cholangitis that were solved with medical treatment. CONCLUSIONS: Our findings indicate that ERCP induce bacteremia in a small group of patients and suggest that prophylactic administration of clindamicine plus gentamicine does not reduce the incidence of bacteremia and cholangitis, and do not support the routine use of prophylactic antibiotics prior to ERCP.

Aged↗

[Disk diffusion method for fluconazole susceptibility testing of Candida spp. isolates].

In order to standardize and evaluate a disk diffusion method with visual reading to detect in vitro fluconazole susceptibility of yeast, 1193 clinical isolates were tested. These included 584 Candida albicans, 196 Candida parapsilosis, 200 Candida tropicalis, 113 Candida glabrata, 50 Candida krusei and 50 Candida spp. and other opportunistic yeasts. The disks were manufactured in the INEI-ANLIS "Dr. Carlos G. Malbrán. The disk diffusion method results were compared to MIC results obtained by the reference CLSI M27-A2 broth microdilution method modified by EUCAST. The interpretative breakpoints for in vitro susceptibility testing of fluconazole were established at: zone diameter > or =16 mm for MIC < or =8 microg/ml (susceptible isolates), between 9 and 15 mm for MIC = 16-32 microg/ml (susceptible dose-dependent isolates), and < or =8 mm for MIC > or =64 microg/ml (resistant isolates). Overall agreement between the two methods was 94.7%, with 0.2% very major errors, and 0.3% major errors. Inter - and intralaboratory agreement was good. The disk diffusion method for drug susceptibility testing of Candida spp. isolates is inexpensive, reliable and reproducible. However, when the inhibition zone diameter is < or =15 mm, it is advisable to test the isolate by the reference microdilution method.

Antifungal Agents↗