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Biomedical subjects

J M Torres

Publications and source records attributed to J M Torres.

At least 19 recordsLinked to original sources

Effects of testosterone on brain mRNA levels of steroid 5alpha-reductase isozymes in early postnatal life of rat.

The enzyme 5alpha-reductase (5alpha-R) (EC 1.3.99.5) exists as two isoforms, 5alpha-R type 1 (5alpha-R1) and 5alpha-R type 2 (5alpha-R2), and both are present in the brain. 5alpha-R1 has been proposed as a constitutive enzyme that essentially plays a catabolic and neuron protective role whereas 5alpha-R2 has been associated with sexually dimorphic functions of the male. In this work, we studied the effects of testosterone (T), the masculinizing hormone of the central nervous system (CNS), on mRNA levels of both 5alpha-R isoforms in the prefrontal cortex of male and female rats during the postnatal sexual differentiation of the CNS in the rat, using one-step quantitative RT-PCR coupled with laser-induced fluorescence capillary electrophoresis (LIF-CE). We found an increase in 5alpha-R2 mRNA levels in both male and female rats after T treatment, while 5alpha-R1 mRNA levels were decreased in the same experimental conditions. Our results clearly indicated that T regulates the expression of both 5alpha-R1 and 5alpha-R2 genes in an opposite manner and independently of the sex. This could point to a crucial role of T in the sexual dimorphism for both 5alpha-R isozymes in the neonatal brain. These results open up a new research line that could improve understanding of the role of 5alpha-R isozymes in the physiology of the CNS.

Animals↗

Post-surgical enterococcal meningitis: clinical and epidemiological study of 20 cases.

Enterococcal post-surgical meningitis is an uncommon disease. 20 episodes of nosocomial post-surgical enterococcal meningitis diagnosed between 1994 and 2003 were retrospectively studied. During the period of study 20 cases of post-surgical enterococcal meningitis (60% female, mean age 55+/-18 y, range 16-78 y) were reviewed. The mean time between admission at the hospital and surgery was 26 (SD = 15) d (range 7-61 d). The most frequent underlying diseases were: intracerebral haemorrhage (55%), brain neoplasms (25%), head trauma (15%) and hydrocephalus (5%). 11 patients had previously received antibiotic treatment. The isolates identified were Enterococcus faecalis (n = 18) (90%), E. faecium (1) and E. durans (1). 11 patients had polymicrobial infections. The treatment most frequently used was vancomycin alone or with other antibiotics (11). In 5 patients intrathecal vancomycin (20 mg/d) was also added. The mortality rate was not different in intrathecally treated patients. Cerebrospinal fluid (CSF) devices were removed in 8 patients. Four patients died due to the infection. Mortality was significantly associated with lack of removal of the CSF devices (p = 0.04). Enterococcal spp. are a cause of nosocomial meningitis associated with neurosurgical procedures and the presence of neurological devices.

Adolescent↗

Steroid 5alpha-reductase isozymes in the adult female rat brain: central role of dihydrotestosterone.

The enzyme 5alpha-reductase (5alpha-R) (EC 1.3.99.5) exists as two isoforms, 5alpha-R type 1 (5alpha-R1) and 5alpha-R type 2 (5alpha-R2). 5alpha-R1 has been associated with catabolic functions whereas 5alpha-R2 has been associated with sexually dimorphic functions of the male. We recently demonstrated that both 5alpha-R isozymes are present in the central nervous system (CNS) of the adult male rat and are regulated in an opposing way by androgens. This finding raises the question as to whether both isozymes play a role in the sexual dimorphism of the CNS, besides other functions. To test this hypothesis, it is essential to study the regulation of both isozymes by androgens in the female. In this work, we studied the effects of testosterone (T) and dihydrotestosterone (DHT) on mRNA levels of both 5alpha-R isoforms in the prefrontal cortex of the adult female rat by one-step quantitative RT-PCR coupled with laser-induced fluorescence capillary electrophoresis. Our results demonstrate for the first time that 5alpha-R2 mRNA is slightly regulated by T and DHT in females. Surprisingly, 5alpha-R1 mRNA is not regulated by T in the intact female, whereas it is very positively regulated by DHT, a more potent androgen than T. These data indicate the great sexual dimorphism in the CNS with respect to both 5alpha-R isozymes, and suggest a crucial role of DHT in the sexual dimorphism of the CNS in the female. These results open up a new research line that may lead to a better understanding of the physiology of the CNS.

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

Transgenic mice expressing bovine PrP with a four extra repeat octapeptide insert mutation show a spontaneous, non-transmissible, neurodegenerative disease and an expedited course of BSE infection.

Transgenic (Tg) mice carrying four extra octapeptide repeats (OR) in the bovine PrP gene (10OR instead of 6) have been generated. In these mice, neuropathological changes were observed depending upon the level of transgene expression. These changes primarily involved a slowly advancing neurological disorder, characterized clinically by ataxia, and neuropathologically, by vacuolization in different brain areas, gliosis, and loss of cerebellar granule cells. Accumulation of insoluble bovine 10OR-PrP (bo10OR-PrP) was observed depending on the level of expression but no infectivity was found associated with this insoluble form. We also compared the behavior of bo6OR-PrP and bo10OR-PrP Tg mouse lines in response to BSE infection. BSE-inoculated bo10ORTg mice showed an altered course of BSE infection, reflected by reduced incubation times when compared to bo6ORTg mice expressing similar levels of the wild type 6OR-PrP. In BSE-inoculated mice, it was possible to detect PrP(res) in 100% of the animals. While insoluble bo10OR-PrP from non-inoculated bo10ORTg mice was non-infectious, brain homogenates from BSE-inoculated bo10ORTg mice were highly infectious in all the Tg mouse lines tested. This Tg mouse model constitutes a new way of understanding the pathobiology of bovine transmissible spongiform encephalopathy. Its potential applications include the assessment of new therapies against prion diseases.

Animals↗

Histoplasmosis infection in Spanish travelers to Latin America.

The aim of the study presented here was to assess the incidence of histoplasma infection in a cohort of 342 individuals in Spain who had traveled to Latin America for the first time. The histoplasmin skin test was positive in 20% of the travelers, and Central America posed a higher risk for infection than South America (p=0.013). Sleeping outdoors (p=0.031) and the duration of travel (p=0.016) were also identified as significant risk factors. Serological testing demonstrated poor overall sensitivity for detecting infection in the travelers, but for the symptomatic acute cases the results were improved. Histoplasmosis must be considered in patients presenting with fever (odds ratio=3.51 [1.52-8.12]) or cough (odds ratio=4.24 [1.32-13.58]) after visiting Latin America. The results of this study have public health implications and indicate the risks of acquiring histoplasmosis should be included in pre-travel counseling.

Adult↗

Vertical transmission of bovine spongiform encephalopathy prions evaluated in a transgenic mouse model.

In this work we show evidence of mother-to-offspring transmission in a transgenic mouse line expressing bovine PrP (boTg) experimentally infected by intracerebral administration of bovine spongiform encephalopathy (BSE) prions. PrP(res) was detected in brains of newborns from infected mothers only when mating was allowed near to the clinical stage of disease, when brain PrP(res) deposition could be detected by Western blot analysis. Attempts to detect infectivity in milk after intracerebral inoculation in boTg mice were unsuccessful, suggesting the involvement of other tissues as carriers of prion dissemination. The results shown here prove the ability of BSE prions to spread centrifugally from the central nervous system to peripheral tissues and to offspring in a mouse model. Also, these results may complement previous epidemiological data supporting the occurrence of vertical BSE transmission in cattle.

Animals↗

Different behavior toward bovine spongiform encephalopathy infection of bovine prion protein transgenic mice with one extra repeat octapeptide insert mutation.

In humans, insert mutations within the repetitive octapeptide region of the prion protein gene (Prnp) are often associated with familial spongiform encephalopathies. In this study, transgenic mice expressing bovine PrP (boTg mice) bearing an additional octapeptide insertion to the wild type (seven octapeptide repeats instead of six) showed an altered course of bovine spongiform encephalopathy (BSE) infection, reflected as reduced incubation times when compared with boTg mice expressing similar levels of the wild-type six-octapeptide protein. In both boTg mouse lines (bo6ORTg and bo7ORTg), incubation times were affected drastically depending on transgene expression levels and the inoculum used. In accordance with the lack of an interspecies barrier to BSE infection, we detected the typical signs of CNS spongiform degeneration by histopathological analysis and the presence of the bovine prion PrP(res) by Western blot or immunohistochemical analyses. When 7OR-PrP(res) was propagated in bo7ORTg mice, a similar earlier onset of clinical signs was observed compared with bo6ORTg mice. Proteins PrP(C) and PrP(res) containing seven octapeptides (7OR-PrP(C) and 7OR-PrP(res)) showed similar protease sensitivity and insolubility in nondenaturing detergents to homologous 6OR-PrP(C) and 6OR-PrP(res). In addition, bo7ORTg mice showed a higher sensitivity than bo6ORTg mice for detecting prion infection in specimens previously diagnosed as negative by conventional biochemical techniques. In the absence of clinical signs of disease, 7OR-PrP(res) could be detected as early as 120 d after inoculation by immunohistochemical and Western blot analyses. These findings may help us improve the current mouse bioassays and understand the role of the octapeptide repeat region in susceptibility to disease.

Age of Onset↗

Precise quantitation of steroid 5alpha lambda pi eta alpha-reductase type 1 mRNA levels by RT-PCR in female rat liver.

The liver is a multifunctional organ capable of steroid hormone catabolism. The steroid metabolizing enzyme activities have been identified in the liver and it has been demonstrated that neonatal testicular androgens irreversibly program several hepatic enzyme activities in the rat including 5alpha-reductase (5alpha-R). In this paper we have applied a quantitative RT-PCR method coupled to laser-induced fluorescence capillary electrophoresis (LIF-CE) to measure the mRNA levels of 5alpha-R type 1 isozyme (5alpha-R1) in the liver of female intact and ovariectomized rats. Both groups were treated with testosterone (T) to study the possible regulation of 5alpha-R1 by androgens in females and to allow comparison with our previous findings in the liver of male rats. Our results demonstrate that the 5alpha-R1 mRNA isozyme is higher in the liver of female rats than in males and that the regulation of 5alpha-R1 mRNA by T is different in the liver of female than in male rats. Finally, our results could point to hepatic 5alpha-Reductase participation in the female not only in the catabolism of steroids with delta4,5 double bond, but also in other physiological functions such as the production of 3alpha,5alpha-reduced metabolites of progesterone and deoxycorticosterone (DOC), potent allosteric modulators of GABA(A) receptors.

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

Alcohol intoxication increases allopregnanolone levels in male adolescent humans.

RATIONALE: Teenage drinking is a cause of growing concern in industrialized countries, where almost 35% of alcohol drinkers are under 16 years old. Increased anxiety, irritability and depression among adolescents may induce them to seek the anxiolytic and rewarding properties of alcohol. Allopregnanolone is rewarding in rodents, and therefore may contribute to the effects of alcohol. OBJECTIVE: In this paper, we studied the effects of acute alcohol intoxication on the plasma levels of allopregnanolone in male adolescents. METHODS: Blood samples were drawn from male adolescents who arrived at the Emergency Department of the Hospital. Two groups were studied: one study group was formed by adolescents who arrived with evident behavioral symptoms of acute alcohol intoxication (AAI) and the other by those arriving for mild trauma (contusions, sprains) after no consumption of alcohol (Controls). RESULTS: Our results demonstrate that AAI significantly increases serum allopregnanolone levels in male adolescents. CONCLUSIONS: Because alcohol and allopregnanolone positively modulate gamma-aminobutyric acid type A (GABAA) receptors, allopregnanolone may play a major role in the anxiolytic and rewarding effects of alcohol, either directly or by influencing the sensitivity of GABAA receptors to alcohol.

Adolescent↗

Alcohol intoxication increases allopregnanolone levels in female adolescent humans.

Teenage drinking is a cause of growing concern in industrialized countries, where almost 35% of alcohol drinkers are under 16 years old. Increased anxiety, irritability, and depression among adolescents may induce them to seek the anxiolytic and rewarding properties of alcohol. We studied the effects of acute alcohol intoxication (AAI) on the plasma levels of progesterone and allopregnanolone in female adolescents. Blood samples were drawn from female adolescents who arrived at the emergency department. One study group was formed by those who arrived with evident behavioral symptoms of AAI and the other by those arriving for mild trauma (contusions, sprains) after no consumption of alcohol (controls). Our results demonstrate that AAI significantly increases serum progesterone and allopregnanolone levels in both follicular and luteal phases of the ovarian cycle. Since alcohol and allopregnanolone positively modulate gamma-aminobutyric acid type A (GABA(A)) receptors, allopregnanolone may play a major role in the anxiolytic and rewarding effects of alcohol, either directly or by influencing the sensitivity of GABA(A)-receptors to alcohol.

Adolescent↗

Early detection of PrPres in BSE-infected bovine PrP transgenic mice.

Transgenic mouse lines expressing different levels of the bovine prion protein gene (boPrP(C)) were generated. Upon infection with BSE prions, all transgenic lines tested exhibited characteristics of the bovine disease. Typical CNS spongiform degeneration was observed by histopathology and presence of PrP(res) could be detected both by Western blot and immunohistochemistry (IHC) assays, confirming for this model the absence of an interspecies barrier to BSE infection. Differences in incubation times post-inoculation depend upon the expression level of boPrP(C) and the amount of prions in the inoculum. In the absence of clinical signs, pathognomonic markers of disease could be detected as early as 150 or 196 days post-inoculation by IHC and Western blot analysis, respectively. This result indicates that prion infectivity in experimental mouse bioassays can be measured earlier by assessing immunologically the presence of PrP(res) in brains from inoculated animals. Although these transgenic mice were also susceptible to sheep scrapie prion infection, the extent of incubation times was considerably longer and PrP(res) was detected in only 70 % of inoculated mice. Interestingly, transgenic mice-propagated sheep scrapie prions displayed distinct biochemical properties when compared to both the original sheep scrapie and transgenic mouse-propagated BSE inoculum.

Animals↗

DHEA, PREG and their sulphate derivatives on plasma and brain after CRH and ACTH administration.

The term neurosteroids applies to steroids that are synthesized in the nervous system, either de novo from cholesterol or from steroid hormone precursors. RIA was used to determine plasma and brain levels of the neurosteroids pregnenolone (PREG), dehydroepiandrosterone (DHEA), and their sulfate derivatives (PREG-S and DHEA-S) in male and female rats after administration of two typical stress hormones: corticotropin-releasing hormone (CRH) and adrenocorticotropin hormone (ACTH). In all cases, the parameters measured were detectable in plasma and brain. PREG, PREG-S, and DHEA increased significantly in plasma and brain after CRH and ACTH administration in males and females. Because neurosteroids play an important role in mammalian physiology, including that of humans, stress situations may alter the physiological functions regulated by these neurosteroids.

Adrenocorticotropic Hormone↗

The antimicrobial properties of different strains of Lactobacillus spp. isolated from kefir.

The characteristics of 58 strains of Lactobacillus spp. isolated from kefir were studied. These strains were tested for adherence to human enterocyte-like Caco-2 cells, resistance to acidic pH and bile acid, antimicrobial activities against enteropathogenic bacteria and inhibition of Salmonella typhimurium attachment to Caco-2 cells. The best probiotic properties were observed in L. acidophilus CYC 10051 and L. kefiranofaciens CYC 10058. L. kefiranofaciens CYC 10058 produced an exopolysaccharide, which revealed that it was closely related to kefiran, a polysaccharide with antitumoral properties. This is the first in vitro study about the antimicrobial characteristics of the Lactobacillus population of kefir.

Antibiosis↗

Differential regulation of steroid 5alpha-reductase isozymes expression by androgens in the adult rat brain.

The enzyme 5alpha-reductase (5alpha-R) is present in many mammalian tissues, including the brain. The physiological importance of 5alpha-R in the brain derives from its capability to convert testosterone (T) to a more potent androgen, dihydrotestosterone (DHT), and to convert progesterone and deoxycorticosterone (DOC) to their respective 5alpha-reduced derivatives, precursors of allopregnanolone and tetrahydroDOC, potent allosteric modulators of the gamma-aminobutyric acid receptor (GABA(A)-R). 5alpha-R occurs as two isoforms, 5alpha-R type 1 (5alpha-R1) and 5alpha-R type 2 (5alpha-R2). We studied the effects of T and DHT on the mRNA levels of both 5alpha-R isozymes in the prefrontal cortex of the adult rat, using an accurate and precise method that combines the high specificity of one-step quantitative RT-PCR with the sensitivity of capillary electrophoresis. Our results demonstrate that both isozymes of 5alpha-R are expressed in the cerebral cortex of adult rats. The gene expression of 5alpha-R type 2 is under the positive control of T and DHT. The gene that codes for 5alpha-R type 1 is not constitutive, because its expression is negatively regulated by T and DHT. These results open up a new research line that may lead to a better understanding of the role of 5alpha-R isozymes in the physiology of the central nervous system.

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

Magnetic relaxation of interacting co clusters: crossover from two- to three-dimensional lattices.

The influence that dipole-dipole interactions exert on the dynamics of the magnetization of nanometer-sized Co clusters has been studied by means of ac and dc susceptibility experiments. These clusters grow in a quasiordered layered structure, where all relevant parameters can be tailored and measured independently. Our data show without ambiguity that the magnetic relaxation becomes slower as the degree of interaction increases. The effective activation energy increases linearly with the number of nearest neighbor clusters, evolving from the value for a 2D layer to the fully 3D behavior, which is nearly reached for five layers. The experimental results agree quantitatively with the predictions of a simple model.

Journal Article↗

ALS and PDC of Guam: forty-year follow-up.

BACKGROUND: It was noticed in the mid-1950s that the incidence of ALS and parkinsonism--dementia complex (PDC) were much higher on Guam than anywhere else in the world. In 1958, a registry of patients and controls was established to ascertain the familial and genetic aspects of these diseases. Patients and individually matched controls and their relatives were registered from 1958 to 1963. The registry was updated and analyzed in 1998 through 1999. OBJECTIVE: To ascertain whether first-degree relatives of patients had a higher risk for developing ALS or PDC than relatives of controls. METHODS: During the period of 1958 to 1963, 126 new patients and 126 individually matched controls and their respective first-degree relatives and spouses were evaluated neurologically and registered. Forty years later, the number of new cases among the patient and control relatives were compared to an expected number of new cases based on the age- and sex-specific incidence of ALS and PDC in the population at large. RESULTS: From 1958 to 1999, there were 102 new ALS or PDC cases among relatives of patients and 33 among relatives of controls. These values were compared with the derived expected values. There were more observed than expected new cases among patients' relatives, and less observed cases than expected among the controls' relatives. CONCLUSIONS: Relatives of patients with ALS or PDC have significantly higher risks for developing the disease than the Guamanian population, whereas relatives of controls have significantly lower risks.

Aged↗

A rapid method for 90Sr determination in the presence of 137Cs in environmental samples.

A rapid method for the determination of 90Sr in the presence of 137Cs using the Cherenkov radiation technique is described. The contribution of 137Cs to gross Cherenkov radiation (90Y + 137Cs) was examined for 137Cs /90Sr ratios ranging from 0.09 to 2.50 for 137Cs activities ranging from 2 to 1,211 Bq. Results from direct Cherenkov radiation measurement and results after radiochemical separation of 90Y from 90Sr for samples containing both 90Sr and 137Cs were compared. Errors below 5% were obtained for 137Cs /90Sr ratios lower than 1, when no separation was performed, independently of the activity level. However, errors between 10% and 35% were obtained for 137Cs/90Sr ratios higher than 1. In order to determine 90Sr activity in the presence of 137Cs using the Cherenkov technique, a multiple linear regression analysis model was established to correct the data for 137Cs content. The mathematical correction proposed was validated using 66 artificially contaminated lettuce samples in a laboratory experiment by taking into account the activity levels of 137Cs and 90Sr and the radionuclide ratios. Comparison of mathematically corrected radionuclide ratios with the results obtained without correction shows that, for radionuclide ratios higher than 1, error values for measuring 90Sr activity using the mathematical model were much smaller than when no radiochemical separation was performed. On the other hand, for ratios lower than 1, error values when measuring 90Sr activity with radiochemical separation were smaller than when mathematical correction was performed. In spite of this, the mathematical correction is an appropriate way of reducing the time needed to determine radiostrontium using the Cherenkov radiation technique. The method proposed could be a powerful tool for environmental research whenever the contents of 90Sr and 137Cs have to be determined.

Cesium Radioisotopes↗