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Biomedical subjects

E Ramírez

Publications and source records attributed to E Ramírez.

At least 37 records · Page 2Linked to original sources

Androgenic and anti-androgenic effects of progesterone derivatives with different halogens as substituents at the C-6 position.

The pharmacological activities of four pregnane derivatives: 17alpha-hydroxy-16beta-methylpregna-4,6-diene-3,20-dio ne (7), 17alpha-acetoxy-16beta-methylpregna-4,6-diene-3,20-dio ne (8), 17alpha-acetoxy-6-bromo-16beta-methylpregna-4,6-diene- 3,20-dione (10), and 17alpha-acetoxy-6-chloro-16beta-methylpregna-4,6-diene -3,20-dione (11), were determined. The derivatives were evaluated on gonadectomized male hamster flank organs and seminal vesicles. The results indicate that topical applications of testosterone (T) on the flank organs increased the diameter of the pigmented spot. Similarly, the same phenomenon occurred on the glands treated with compound 11, whereas compound 10 decreased the size of the spot significantly. In this study, we determined the effects of several new steroids on the conversion of T to DHT in flank organs and seminal vesicles. The results show that compound 10 inhibited T conversion to DHT, but compound 11, at a dose of 200 microg, stimulated T conversion in both flank organs and seminal vesicles. However, when 2 mg of compound 11 was applied, it inhibited the conversion of T to DHT, suggesting that this compound also represses gonadotropin release. The difference between compounds 10 and 11 involves the electronegativity of the halogen at the C-6 position of the progesterone skeleton. These data clearly indicate that by decreasing the electronegativity of the halogen at C-6 (compound 10), 5alpha-reductase is inhibited in both tissues and at different pHs. On the other hand, when the electronegativity of the halogen atom was increased (11), there was a much lower inhibitory effect on the conversion of T to DHT.

Androgen Antagonists↗

Synthesis and pharmacological evaluation of 4-halo progesterone derivatives as antiandrogen.

The pharmacological activity of eight pregnane derivatives 17-alpha acetoxyprogesterone 9, 17-alpha acetoxy-4, 5-epoxypregnan-3, 20-dione 10, 17-alpha acetoxy-4-chloro-4-pregnene-3, 20-dione 11, 17-alpha acetoxy-4-bromo-4-pregnene-3, 20-dione 12, 17-alpha hydroxy-4-bromo-4-pregnene-3, 20-dione 13, 4-chloro-17-alpha hydroxy-4-pregnene-3, 20-dione 14, 17-alpha benzoyloxy-4-bromo-4-pregnene-3, 20-dione 15 and 17-alpha benzoyloxy-4-chloro-4-pregnene-3, 20-dione 16 was determined. These compounds were evaluated as antiandrogens on gonadectomized hamster seminal vesicles. The pharmacological data in this study indicate that compounds 15 and 16 having a C-17 benzoyloxy moiety showed the highest antiandrogenic activity as measured by the reduction of the weight of the seminal vesicles, followed by the steroids 11 and 12 (17-alpha acetoxy group). The free alcohols 13 and 14 exhibited a lower antiandrogenic activity. Apparently, the ester moiety at C-17 is a necessary requirement for the presence of high antiandrogenic activity. Shows the inhibitory effect on the conversion of testosterone (T) to DHT, of the above described steroids as measured by the amount of produced DHT 2 expressed as pmoles of DHT/g of protein/h. Steroids 11, 12 and 16 showed a much higher inhibitory activity on the conversion of testosterone (T) to dihydrotestosterone (DHT) than presently used finasteride 3.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

[Immune status against measles and rubella among 4 Chilean groups of different ages].

BACKGROUND: Results of clinical and epidemiological studies confirm that no cases of measles have occurred in Chile since 1993. However, since covering of vaccination programs do not exceed 95%, an immunological surveillance for this disease is warranted. AIM: To know the immune status against measles and rubella in the Chilean population. MATERIAL AND METHODS: A serological census of a representative sample of communities with high (90% or more) or low immunization coverings was performed. Four sub samples along the country were selected: 122 children aged 18 months of age (stratum A), 1,276 children attending the first years of basic school (stratum B), 899 teenagers in their last high school year (stratum C) and 399 women attending a family planning clinic (stratum D). IgG antibodies against measles and rubella were measured using ELISA and hemagglutination inhibition techniques, respectively. RESULTS: Antibodies against measles and rubella were found in 96% and 94% of study subjects. No differences in these titres were found between different strata or communities with high or low vaccination covering. There is a high percentage of positive antibodies against measles among children of 18 months of age and a high percentage of antibodies against rubella among teenagers and women in family planning. Only 3% of the sample had not received any vaccine at the moment of the study. CONCLUSIONS: The high prevalence of antibodies against rubella allows to conclude that it is not necessary to consider this antigen in the next vaccination campaign. Due to the high prevalence of antibodies against measles, only the population older than 20 years old should be affected by the disease if this virus enters the country.

Adolescent↗

Steroidal antiandrogens and 5alpha-reductase inhibitors.

The purpose of this work is to synthesize a pregnane derivative with a high antiandrogenic effect or a high inhibitory activity for the enzyme 5 alpha-reductase type 2. Benign prostatic hyperplasia and prostate cancer are androgen dependent diseases which afflict a large percentage of the male population. Dihydrotestosterone 3, a 5 alpha-reductase metabolite of testosterone 2 has been implicated as a causative factor in the progression of these diseases, largely through the clinical evaluation of males who are genetically deficient of steroid 5 alpha-reductase enzyme. As a result of this study, the inhibition of this enzyme has become a pharmacological strategy for the design and synthesis of new drugs. The advent of finasteride 22 "figure 5" a 5 alpha-reductase inhibitor, has greatly alleviated the symptoms associated with benign prostatic hyperplasia. On the other hand, the discovery of cyproterone acetate 4 "figure 2" alone or in combination with the antiandrogens flutamide 14 "figure 3" or bicalutamide 21 has greatly reduced the misery of prostate cancer. Prostate cancer kills about 40,000 men in the USA and approximately 400,000 prostatectomies are performed each year. In our laboratory we have recently synthesized ten new progesterone derivatives 17 alpha-acyloyloxy-6-halo (chloro, bromo) 16 beta-methyl-4, 6-pregnadiene-3, 20-diones (54a-54e and 55a-55e), "figure 10". These steroids were evaluated as antiandrogens and exhibited a much higher activity than the commercially available cyproterone acetate 4. The same compounds were also evaluated as 5 alpha-reductase inhibitors and showed a slightly higher inhibitory activity than that of finasteride 22, the drug of choice today for the treatment of benign prostatic hyperplasia In another study we synthesized several new 4-halo (bromo and chloro) 17 alpha-benzoyloxy and also 4-halo-17 alpha-acetoxy progesterone derivatives (58-63) "figure 13". These compounds were prepared from the commercially available 17 alpha-acetoxy progesterone 56. The pharmacological evaluation of these steroids "figure 14" indicated that the 17 alpha-benzoyloxy derivatives (4-chloro and bromo) 62 and 63 were very potent antiandrogens. On the other hand, the 4-halo (bromo and chloro) 17 alpha-acetoxy (58, 59) and the 17 alpha-benzoyloxy-4-chloro analog 63 showed a very high inhibitory activity for the enzyme 5 alpha-reductase type 2 "figure 15".

Adrenergic Antagonists↗

[HTLV-I tax gene on the etiological identification of tropical spastic paraparesis. A clinical, serological and polymerase chain reaction (PCR) study in 72 patients].

BACKGROUND: Tropical spastic paraparesis (TSP) is an endemic disease in Chile. In most countries, only 50% of patients are seropositive to HTLV-I. However, new studies suggest that seronegative TSP is also associated with HTLV-I. AIM: To describe clinical and virological features of seronegative patients with TSP. PATIENTS AND METHODS: Seventy two Chilean patients with TSP, studied by clinical, radiological and laboratory methods during 1998, are reported. The determination of antibodies to HTLV-I was accomplished by ELISA, immunofluorescence and Western-blot analysis. Polymerase chain reaction for tax and 5'Ltr genes was made using primers SK 43-44, LTR1 and LTR6. RESULTS: Thirty one patients were HTLV-I positive and 41 were negative. No clinical, radiological or laboratory differences were observed between both groups. In seropositive patients, tax and 5'ltr viral gene sequences of the HTLV-I provirus were detected in DNA of peripheral blood mononuclear cells. In seronegative cases, sequences of tax gene were detected, exclusively, in 18 of 41 patients. CONCLUSIONS: These results confirm an association with HTLV-I infection in 43.9% of the TSP seronegative patients. These findings support the hypothesis that a defective provirus infects peripheral blood mononuclear cells in seronegative cases of TSP. The importance tax gene in the diagnosis of the TSP is also emphasized.

Adult↗

Distinct mechanisms of antibody-mediated enzymatic reactivation in beta-galactosidase molecular sensors.

The antibody-mediated reactivation of engineered Escherichia coli beta-galactosidases [Benito et al. (1996) J. Biol. Chem. 271, 21251-21256] has been thoughtfully investigated in three recombinant molecular sensors. Proteins M278VP1, JX772A and JX795A display the highly antigenic G-H loop peptide segment of foot-and-mouth disease virus VP1 protein, accommodated in different solvent-exposed loops of the assembled tetramer. These chimaeric enzymes exhibit a significant increase in enzymatic activity upon binding of either monoclonal antibodies or sera directed against the inserted viral peptide. In JX772A but not in M278VP1, the Fab 3E5 antibody fragment promotes reactivation to the same extent as the complete antibody. On the other hand, M278VP1 Km is reduced by more than 50% in the presence of activating serum, this parameter remains invariable in JX772A and it is only slightly modified in JX795A. In these last two proteins, significant k(cat) variations can account for the increased enzymatic activity. Alternative reactivation mechanisms in the different beta-galactosidase probes are discussed in the context of the bacterial enzyme structure and its tolerance to antibody-induced conformational modifications.

Amino Acid Sequence↗

[Familial form of tropical spastic paraparesis. Report of 4 families].

We report eight patients with familial tropical spastic paraparesis belonging to four families. The diagnosis was reached by clinical, radiological and electrophysiological studies. Human lymphotropic virus type I infection was confirmed by ELISA, immunofluorescence essays. Western blot and polymerase chain reaction in DNA of peripheral blood mononuclear cells, using primers for tax and 5'ltr genes. In all these families there was a vertical transmission of the disease from the first to the second generation. All patients improved their spastic gait after prednisone treatment. Among patients of the second generation, all had dacrysialoadenitis, three had leukemia like lymphocytes in the blood smear, two had mycosis fungoides and one had hepatic cirrhosis.

Adolescent↗

Viral spread within ageing bacterial populations.

The viral spread within isolated host populations has been studied throughout the growth of P22-infected Salmonella cell colonies. By using an integration mutant of this bacteriophage, horizontal and vertical transmission have been analyzed independently. The data obtained show that both strategies are not simultaneous but consecutive during the colony development. Lytic cycles are tightly repressed during the exponential cell growth but stimulated in independent colonies with remarkable synchrony when the cell division rate decreases. The coincidence of the viral outburst and the decay of bacterial replicative fitness is a new example of the extreme viral competence in exploiting the host cells as dissemination vehicles for viral genomes.

Adaptation, Physiological↗

Allele frequency distributions of 13 PCR-based systems in a population from North-East Spain.

Population data studies were carried out on a Caucasian population from North-East Spain (n = 129-292 individuals) for 13 PCR-based polymorphic DNA loci: six short tandem repeat loci (HumTH01, HumTPOX, HumCSF1PO, HumF13A01, HumFES/FPS, HumvWFA31), the six PM loci (HLA-DQ alpha, LDLR, GYPA, HBGG, D7S8, GC) and one variable number tandem repeat locus (D1S80). The genotypes distributions were in accordance with Hardy-Weinberg expectations. The combined use of the 13 polymorphic systems provides a high power of discrimination and power of exclusion for use in forensic casework and paternity testing.

Alleles↗

Genetic characterization and phylogeny of Andes virus and variants from Argentina and Chile.

Andes virus, one of five hantaviruses known to cause hantavirus pulmonary syndrome (HPS), emerged in 1995 in southwestern Argentina (López et al. (1996) Virology 220, 223-226). The complete nucleotide sequence of Andes virus S genome segment was determined and compared with sequences of viral RNAs in autopsy tissues of more recently reported HPS cases from southwestern Argentina and south of Chile (cases ESQ H-1/96 and CH H-1/96). Andes virus S segment was found to be 1876 nucleotides in length and to encode the nucleocapsid protein (N), 428 amino acids in length. S segment analysis also revealed a long 5' non-coding region (547 nucleotides) which displays three copies of an octanucleotide sequence repeat. Comparisons of S segment sequences of ESQ H-1/96 and CH H-1/96 (82% of the entire genome sequence) with the corresponding sequences of Andes virus revealed identities of 97.2% and 98.5%, respectively. Sequence motifs identical and in the same positions as exhibited in Andes virus 5' non-coding region were found in both, ESQ H-1/96 and CH H-1/96 sequences. Three genome fragments of the M segment sequence of the viruses (representing approximately 34% of the entire sequence) were also analyzed. Comparisons of S and M segment sequences of Andes virus with the corresponding sequences of ESQ H-1/96 showed S and M segment identities which differ by less than 1.4%. Andes virus and CH H-1/96 have S segments that differ by 1.5% from one another while their M segment fragments differ by 5.5-8.2%. Phylogenetic analysis showed that Andes virus along with ESQ H-1/96 and CH H-1/96 form a distinct lineage within the clade containing Bayou and Black Creek Canal viruses. It also showed that Andes virus branch of trees derived from comparisons of S or M sequences differed. It is concluded that Andes virus variants causing HPS circulate east and west of the Andes mountains.

Amino Acid Sequence↗

[New form of subcortical dementia: encephalopathy due to infection with human lymphotropic T virus (HTLV-1). Clinical case].

We report a 45 years old female with a HTLV-I associated myelopathy, followed up for 10 years who, five years ago, developed personality changes and intellectual deterioration, assessed with the Wais-Benton test. She also had alterations in the electroencephalogram and a nuclear magnetic resonance imaging of the brain showed hypodensity in T1 and hyperdensity in T2 subcortical regions. The progression of intellectual impairment was related to an increase in proviral DNA, assessed with polymerase chain reaction.

Dementia↗

Genetic structure of autochthonous populations of Meso-America: Mexico.

We analyze the possible effect of gene flow on the genetic structure of present-day Mexicans. For this purpose we reviewed previous admixture estimates for various Indian and Mestizo groups. Several facts seem clear: (1) There are no pure Indian groups in Mexico, because all Indian groups show variable degrees of admixture, mostly with whites (range, 0.088 in the Huichol to 0.373 in the Huasteco); (2) the main ancestral contribution to the noncoastal lower middle class Mestizo populations is Indian (above 50%) so that from a genetic standpoint Indians and lower middle class Mestizos are not much different; and (3) black ancestry is quite high on the coasts, ranging from 0.127 to 0.405 on the east coast, and is present in other Mestizos, ranging in large urban centers from 0.027 in Oaxaca to 0.107 in Puebla and in smaller cities from 0.08 in Tlaxcala to 0.181 in Cuanalán.

Emigration and Immigration↗

Hartmannella vermiformis isolated from the cerebrospinal fluid of a young male patient with meningoencephalitis and bronchopneumonia.

Meningoencephalitis and bronchopneumonia were documented in a patient from Peubla, Mexico. The patient began with symptoms and signs of a common flu and 12 days after the onset of his disease he was admitted to the hospital presenting symptoms and signs of meningoencephalitis. The clinical course evolved into an endocraneal hypertension syndrome with bronchopneumonia, coma and death. Wide-spectrum antibiotics, immunosuppressive and anti-tuberculosis therapy were unsuccessfully administered. Important antecedents were degree I malnutrition and repeated contact with polluted water. Post-mortem autopsy was not performed. Gram-positive cocci were isolated from the spinal fluid 2 days after admission, and then active amebae were isolated from three different samples of the spinal fluid at days 16, 18 and 19 after admission. Such samples were concentrated and inoculated onto specific culture media. Identification of amebae was based on their morphology and biochemistry. All amebae were Hartmannella vermiformis. Amebae were apparently not the cause of the disease and might be considered as an opportunistic colonizer which may have caused the evolution of the disease to become worse.

Acid Phosphatase↗

Electrochemical impedance spectroscopy of preoxidized MA 956 superalloy during in vitro experiments.

Preoxidation treatment of MA 956 superalloy at 1100 degrees C produces a fine and tightly adherent alpha-alumina layer at the surface, which provides the alloy with an excellent barrier against a great variety of aggressive environments. In this work the protective capacity of the alumina/alloy system is evaluated in a physiological medium by means of electrochemical impedance spectroscopy. The electrochemical response of the material is modelled by equivalent circuits which provide the most relevant corrosion and protection parameters applicable to MA 956 in both preoxidized and as-received conditions (passivated state). The high protective capacity of preoxidized MA 956 superalloy holds for long-term tests, which indicates that the corrosion phenomena, if any, would be characterized by very slow kinetics. The corrosion resistance of the preoxidized material is at least two orders of magnitude higher than that of the non-treated alloy.

Alloys↗

[Seroprevalence of HTLV-I in relatives of patients with spastic paraparesis (HAM/TSP and PEP)].

The seroprevalence of HTLV-1 was studied in parents, brothers, siblings and sexual partners of 147 patients with spastic paraparesis associated to HTLV-1 (HAM/TSP) and 84 patients with HTLV-1 negative spastic paraparesis (SP). Seroprevalence was 29.1% for HAM/SP and 0% for SP relatives (p < 0.001); the last figure is similar to that of the general population. Seroprevalence in sexual partners was 65%, suggesting that sexual intercourse is the principal route of transmission. Likewise, seroprevalence in siblings of mothers with HAM/TSP or HTLV-1 positive was 17.6%, suggesting a high maternal transmission.

Adolescent↗

[Anti HTLV-I antibody titers in seropositive infected individuals].

The aim of this study was to determine anti HTLV-I antibody titers in seropositive symptomatic and asymptomatic infected subjects. One hundred seven infected subjects (47 with spastic paraparesis and 60 asymptomatic) were studied. HTLV-I antibodies were determined using indirect immunofluorescence in cells infected with the retrovirus. The mean titer was 1/234 in asymptomatic subjects and 1/2138 in symptomatic patients (p < 0.001). These results suggest an association between HTLV-I antibody titers and clinical stage of infected subjects.

Adult↗