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Biomedical subjects

M Rubio

Publications and source records attributed to M Rubio.

At least 37 records · Page 2Linked to original sources

Drug glucuronidation and hepatic lipid microsomal membrane profile in cholestatic rats followed paracetamol intoxication.

The uridin-diphosphoglucuronyl-transferase (UDP-GT) is a membrane-bound enzyme responsible for glucuronidation of endogenous and exogenous compounds. This work established the UDP-GT activity and its lipid membrane microenvironment in two experimental models: acute paracetamol intoxication, and cholestasis followed by acute paracetamol intoxication. Cholestasis was performed by bile duct ligation. After 7 days animals were injected with paracetamol (BDL-APAP group). Sham-operated rats were injected at day 7 with paracetamol (APAP group). Cholestatic and sham-operated rats injected with vehicle (BDL and control groups). UDP-GT activity was measured by a kinetic method for different substrates. Microsomal membrane phospholipid composition, cholesterol content and ultrastructure were determined. BDL-APAP group showed an increment in the UDP-GT activity except for chloramphenicol, morphine and paracetamol if compared to controls and to BDL group. The same increment was observed when BDL-APAP was compared to APAP except for chloramphenicol and lorazepam. Between BDL and APAP groups similar levels of activity were detected except for paracetamol. Microsomal phospholipid profile: phosphatidylcholine showed the lowest content in the BDL group, with a significant recovery in the BDL-APAP and APAP groups. Phosphatidylserine was markedly decreased in the APAP group compared to the rest and phosphatidylinositol was decreased in all the groups if compared to control values. An increment of phosphatidylethanolamine was seen in the APAP and BDL-APAP groups if compared to BDL and control values. A significant increment of microsomal cholesterol content was seen in BDL. Under these conditions, a different lipid microenvironment is produced, resulting in an increment of the enzyme activity for a variety of substrates.

Acetaminophen↗

Immunohistochemical evidence of the presence of aromatase P450 in the rat hypophysis.

In order to analyze whether aromatase is present in the hypophysis of adult rats, we have performed an immunohistochemical study in young adult male and female rats. Our study has revealed that the hypophysis of adult rats contains aromatase, although marked differences are found between the sexes. The hypophyses of male rats have cells immunoreactive for the enzyme, 34.40% of these hypophyseal cells showing reaction. By contrast, cells from female rats show very little reaction, only 0.84% of them being reactive. No significant differences in the percentage of immunoreactive cells between one phase and another are observed during the estrous cycle. Our results point to the immunohistochemical expression of aromatase in the hypophysis of adult rats and at the same time suggest that its expression is sex-dependent. The enzyme may therefore be involved in the regulation of adenohypophyseal cytology by androgens.

Amino Acid Sequence↗

Lidocaine and monoethylglycinexylidide serum determinations to analyze liver function of cirrhotic patients after oral administration.

Our aim was to compare standard liver function tests (serum bilirubin, serum albumin and prothrombin concentration), with lidocaine and monoethylglycinexylidide pharmacokinetic parameters, after oral lidocaine administration, to assess hepatic function of cirrhotic individuals. Twenty-one consecutive cirrhotic patients, nine consecutive acute hepatitis patients, and nine healthy individuals received oral lidocaine. Lidocaine and monoethylglycinexylidide serum concentrations were determined by the TDx system. Cirrhotic patients had higher lidocaine and lower monoethylglycinexylidide serum concentrations and differences in its pharmacokinetic variables, compared to control and hepatitis groups (P < 0.05). Sensitivity of lidocaine serum determinations (100%) was greater than sensitivity of serum bilirubin (57%), serum albumin (62%), and prothrombin concentrations (43%) and monoethylglycinexylidide serum concentrations (57%) in differentiating cirrhotic individuals from controls. In conclusion, after oral administration, lidocaine and monoethylglycinexylidide pharmacokinetic parameters are significantly altered in cirrhotic patients compared to normal and acute hepatitis subjects. Lidocaine pharmacokinetic parameters would be better than those of monoethylglycinexylidide and standard liver function tests in the evaluation of liver function of cirrhotic patients.

Administration, Oral↗

Bacteremic pneumonia due to Staphylococcus aureus: A comparison of disease caused by methicillin-resistant and methicillin-susceptible organisms.

We performed a prospective study of all patients with bacteremic pneumonia due to Staphylococcus aureus over a period of 6 years during an outbreak of methicillin-resistant S. aureus (MRSA). Patients with bacteremic pneumonia due to MRSA (32 cases) or methicillin-susceptible S. aureus (MSSA; 54 cases) were compared. The patients with MRSA pneumonia were older and were more likely than those with MSSA pneumonia to have predisposing factors for acquisition of the infection. There were no differences in clinical findings, radiological pattern, or complications in clinical evolution among patients with MRSA and MSSA pneumonia. Mortality was significantly higher among MSSA-infected patients treated with vancomycin than among those treated with cloxacillin (47% vs. none; P<.01). Multivariate analysis (stepwise logistic regression method) showed a relationship between mortality and the following variables: septic shock (odds ratio [OR], 61), vancomycin treatment (OR, 14), and respiratory distress (OR, 8).

Adult↗

Serotonin in golden hamster testes: testicular levels, immunolocalization and role during sexual development and photoperiodic regression-recrudescence transition.

Serotonin (5-HT) is found in the gonads and accessory reproductive organs of several species. The golden (Syrian) hamster is a seasonal breeder. Exposure of male adult hamsters to short days for 14 weeks results in a severe gonadal regression, while after a photoinhibition period of 22 weeks a spontaneous testicular recrudescence occurs. The aim of this study was to investigate the presence of 5-HT and its major metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the gonads of golden hamsters, its immunolocation and its physiological role in the testis. The influence of age and photoperiod was also analyzed. Hamsters of 23, 36, 46, 60 and 90 days of age were kept in long photoperiod (LP: 14:10 h light/dark), and adult animals were exposed either to LP or to short photoperiod (SP: 6:18 h light/dark) for 14 and 22 weeks. Testicular parenchyma and capsule levels of 5-HT and 5-HIAA increased significantly at ages of 36 and 60-90 days, but decreased markedly during the exposure of adult hamsters to SP for 14 and 22 weeks. Mast cells were found exclusively in the testicular capsule. The testicular number of mast cells increased concomitantly with age, but decreased in adult hamsters exposed to SP. Mast and Leydig cells presented 5-HT-positive immunoreactivity. During sexual maturation as well as during the transfer of adult hamsters from LP to SP, the 5-HIAA/5-HT ratio showed the highest values in active adult animals, indicating that the increase in testicular 5-HT levels in adulthood is accompanied by an augment in 5-HT turnover. In vitro basal and hCG-stimulated testosterone production was significantly inhibited in presence of physiological concentrations of 5-HT. In conclusion, the present studies demonstrate the existence of 5-HT in mast cells and Leydig cells of hamster testes, as well as describe an inhibitory action of this neurotransmitter on gonadal testosterone production. Furthermore, the age-dependent and photoperiodic-related changes detected in testicular 5-HT levels suggest that this neurotransmitter might act as an important local modulator of the action of gonadotropins on steroidogenesis during sexual development and during the photoperiodic regression-recrudescence transition in the golden hamster.

Aging↗

[Bacteremia by Staphylococcus aureus: analysis of 311 episodes].

BACKGROUND: The aim of this study was to set up the differences between nosocomial and community acquired S. aureus bacteremia, to identify the features of the patients at high risk of endocarditis and to define the characteristics of the patients with methicillin resistant S. aureus (MRSA). METHODS: We prospectively studied 311 cases of S. aureus bacteremia detected at our hospital during a four-year period. RESULTS: Nosocomial acquisition of bacteremia was found in 63% of the cases, 45% of which were caused by MRSA. Nosocomial bacteria generally presented in older patients with more severe underlying conditions and a higher prevalence of invasive procedures than patients with the community-acquired disease. Likewise, the primary focus of infection was identifiable in most of the nosocomial episodes and mortality was also higher. Endocarditis presented in 19% of the bacteremia episodes and almost 90% of patients with endocarditis were intravenous drug users (IDU). The risk of endocarditis in this group was 64% whereas it was only 3% in non-IDU patients. Overall mortality was 33% and mortality directly due to the bacteremia was 22%. CONCLUSIONS: IDU patients were at high risk of endocarditis but most had a favourable outcome. Bacteremia was community-acquired in these patients and they rarely presented MRSA bacteremia. Patients with previous valvular diseases were at high risk of endocarditis and had a high mortality. Non-IDU patients with community-acquired bacteremia were at a low risk of endocarditis, regardless of whether a primary focus of infection had been identified or not. Mortality was lower in this group than in patients with nosocomial bacteremia and there were no cases of MRSA bacteremia. Mortality was higher in patients treated with vancomycin than in patients treated with other antibiotics active against S. aureus.

Adult↗

[Immunoglobulin rearrangement in the differential diagnosis of primary gastric lymphoma].

BACKGROUND: The traditional methods to distinguish Chronic Follicular Gastritis and Primary Gastric Lymphoma do not allow an adequate definitive diagnosis in a significant number of cases. The molecular Biology diagnostic methods are based on the rearrangement of immunoglobulin genes. The polymerase chain reaction (PCR) specifically amplifies this rearrangement and allows molecular analysis of minimal tissue samples obtained with endoscopical biopsies. AIM: To test the usefulness of this PCR method in the differential diagnosis between Chronic Follicular Gastritis and Primary Gastric Lymphoma. MATERIAL AND METHODS: We analyzed the endoscopical biopsies of six Chronic Follicular Gastritis cases and eight surgically treated Primary Gastric Lymphoma cases, six with the correct diagnosis in the endoscopical biopsies and two with a diagnosis of Chronic Follicular Gastritis. RESULTS: A policlonal immunoglobulin rearrangement was found in the six cases with Chronic Follicular Gastritis. A monoclonal arrangement was found in 5 of 6 biopsies with the diagnosis of Primary Gastric Lymphoma. The same monoclonal rearrangement was observed in the two biopsies incorrectly diagnosed as Chronic Follicular Gastritis. CONCLUSIONS: PCR analysis of immunoglobulin rearrangement is a useful method in the differential diagnosis between Chronic Follicular Gastritis and Primary Gastric Lymphoma.

Chronic Disease↗

IL-15 promotes IL-12 production by human monocytes via T cell-dependent contact and may contribute to IL-12-mediated IFN-gamma secretion by CD4+ T cells in the absence of TCR ligation.

At inflammatory sites, the number of activated bystander T cells exceeds that of Ag-activated T cells. We investigated whether IL-15, a monocyte-derived cytokine that shares several biologic activities with IL-2, may contribute to bystander T cell activation in the absence of IL-2 and triggering Ag. The addition of IL-15 to cocultures of monocytes and T cells stimulates CD4+ but not CD8+ T cells to produce IFN-gamma. IFN-gamma production requires endogenous IL-12, the production of which in turn is dependent upon CD40/CD154 interactions between CD4+ T cells and monocytes. Indeed, non-TCR-activated CD4+ but not CD8+ T cells express significant levels of CD154. IL-15 may enhance IFN-gamma in this system by up-regulating CD40 expression on monocytes and IL-12Rbeta1 expression on CD4+ T cells. Conversely, using neutralizing anti-IL-15 mAb, we show that the ability of IL-12 to augment IFN-gamma secretion is partly mediated by endogenous IL-15. Finally, in the absence of monocytes, a synergistic effect between exogenous IL-12 and IL-15 is necessary to induce IFN-gamma production by purified CD4+ T cells, while IL-15 alone induces T cell proliferation. It is proposed that this codependence between IL-12 and IL-15 for the activation of inflammatory T cells may be involved in chronic inflammatory disorders that are dominated by a Th1 response. In such a response, a self-perpetuating cycle of inflammation is set forth, because IL-15-stimulated CD4+ T cells may activate monocytes to release IL-12 that synergizes with IL-15 to induce IL-12 response and IFN-gamma production.

Adjuvants, Immunologic↗

Atrial natriuretic factor does not affect norepinephrine catabolism in rat hypothalamus and adrenal medulla.

We have previously reported that atrial natriuretic factor (ANF) increases neuronal uptake and endogenous content of norepinephrine (NE) and diminishes neuronal release, synthesis and turn-over of NE in rat hypothalamus and adrenal medulla. The aim of the present work was to study another aspect of NE metabolism and therefore investigate the possible effects of ANF on NE catabolism. The determination of monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT) activity and deaminates metabolites formation were studied in vitro in rat hypothalamus and adrenal medulla slices. Results showed that, in the hypothalamus, 100 nM ANF diminished MAO activity while 10 nM ANF did not modify the enzyme activity. Conversely, 10 and 100 nM ANF reduced MAO activity in adrenal medulla. On the other hand, the atrial factor modified neither COMT activity nor the formation of deaminates metabolites in the hypothalamus and adrenal medulla. Present results as well as previous findings support a putative role for ANF in the modulation of NE metabolism not only in the hypothalamus but also in the adrenal medulla of the rat, affecting the storage, release and uptake of NE but not its catabolism.

Adrenal Medulla↗

Reduced nicotinamide adenine dinucleotide phosphate-diaphorase activity in the paraventricular nucleus of the rat hypothalamus is modulated by estradiol.

Based on previous studies demonstrating that reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase (ND) activity is modulated by estradiol and the discovery of a new subtype of estrogen receptor highly expressed in the paraventricular nucleus of the hypothalamus (PVN), a possible estrogen influence on this activity was investigated in the neuronal populations (magno- and parvicellular) of this nucleus. Cryostat sections were cut and processed for the histochemical detection of the ND activity. Following ovariectomy (14 days), numerical data displayed a slight decrease in the number of ND-neurons, especially in the posterior magnocellular and the medial parvicellular subdivisions, which was reversed after daily treatment with estradiol benzoate. Administration of estradiol benzoate to male rats (14 days) induced a significant increase (P < 0.05) in the number of ND-neurons, mainly at the level of the posterior magnocellular subdivision. These data indicate that paraventricular ND-neurons are influenced by estradiol.

Animals↗

IFN-alpha priming of human monocytes differentially regulates gram-positive and gram-negative bacteria-induced IL-10 release and selectively enhances IL-12p70, CD80, and MHC class I expression.

Administration of IFN-gamma and IFN-alpha may protect or induce autoimmune diseases. Although the in vitro regulation of monokine secretion by IFN-gamma have been extensively studied, the regulatory function of IFN-alpha has not yet been elucidated. We compared IFN-alpha and IFN-gamma, added alone or simultaneously before bacterial stimulation, for the control of monokine release and the expression of costimulatory molecules by human monocytes. Our data show that: 1) IFN-alpha primes monocytes for increased production of IL-10 in response to Staphylococcus aureus Cowan I strain (SAC) but not to LPS, leading to a lack of IFN-alpha priming for TNF-alpha secretion; 2) pretreatment of monocytes with IFN-alpha inhibits LPS- or SAC-induced IL-12p40 production but unexpectedly enhances the release of the biologically active form of IL-12 (IL-12p70); 3) IFN-alpha and IFN-gamma exert an antagonistic effect on LPS- and SAC-induced IL-10 as well as IL-12p40 release, whereas they further enhance IL-12p70 production when added simultaneously; 4) in contrast to IFN-alpha, IFN-gamma primes monocytes to enhance LPS- or SAC-induced TNF-alpha and IL-12 production, but surprisingly, it increases IL-10 production by monocytes following LPS but not SAC stimulation; and finally, 5) IFN-alpha pretreatment selectively up-regulates CD80 and MHC class I expression on monocytes. It is proposed that the outcome of the immune response at the site of inflammation may depend on both the type of bacterial injury (gram-positive or -negative) and of locally produced IFNs, and that the differential and opposite effects of type I and type II IFNs on monocytes may account for the beneficial or detrimental effects of IFN-alpha therapy.

Adjuvants, Immunologic↗

Ozonation Products of Organosolvolytic Extracts from Vegetal Materials.

The ozonation of lignin in an organic solution was used to produce oxyaromatic compounds. Corn (Zea mays) stalk and poplar (Populus deltoides) wood lignin solutions (organosolvolytic juices) obtained from their respective autohydrolyzed materials and an organosolv lignin were treated with ozone, and the time course trend of the identified reaction products was studied. GC/MS and GC/FID were used to identify and quantify (internal standard method) the reaction products. The following acids were identified: glycolic, oxalic, malic, glyceric, p-hydroxybenzoic, and vanillic. In addition, p-hydroxybenzaldehyde, vanillin, syringaldehyde, and hydroquinone were also identified. All the oxyaromatic aldehydes reached maximum yields at short reaction times (between 1 and 8 min). These results were used to determine the ratio between the different phenylpropane units of their constitutive lignins. The ratio of p-hydroxyphenyl:guaiacyl:syringyl units for corn stalk, poplar wood, and organosolv lignins was 5.3:2:1, 0.1:1:1.1, and 0:1:1.1, respectively.

Journal Article↗

Depressed immunity to a Salmonella typhimurium vaccine in mice experimentally parasitized by Taenia crassiceps.

To assess the immunological status of mice parasitized with Taenia crassiceps metacestodes, 6-month old female BALB/c mice experimentally parasitized with T. crassiceps and immunized with Salmonella typhimurium antigens were infected with S. typhimurium virulent bacilli (1.6 x LD50). Both T. crassiceps-parasitized and immunized and parasitized mice showed a very high susceptibility to infection (**P < 0.01) with higher bacteremia than control and immunized-control animals and produced a reduced IgG response to S. typhimurium, antigens (* P < 0.05). This indicates that T. crassiceps is able to preclude development of immunity to S. typhimurium, because appropriate antibody production to a heterologous antigenic stimulus did not take place, and the bacteremia results suggest the parasitosis altered the mononuclear phagocyte system. It has been demonstrated that Taenia solium metacestodes produce a small RNA molecule in culture which suppresses humoral and cellular responses against homologous antigens in mice. We propose that T. crassiceps may be actively synthesizing such a factor, apart from other simultaneously acting immunomodulatory mechanisms, to induce an immunosuppressed state favorable to its development in the host.

Animals↗