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Biomedical subjects

J Palma

Publications and source records attributed to J Palma.

At least 19 recordsLinked to original sources
PubMed2006

Photobiomodulation of pain and inflammation in microcrystalline arthropathies: experimental and clinical results.

OBJECTIVE: This article presents the results of laser therapy in crystal (hydroxyapatite, calcium pyrophosphate, and urates) deposition-induced arthritis in rats and the clinical applications in humans. BACKGROUND DATA: Microcrystalline arthropathies are prevalent among geriatric patients, who are more vulnerable to the side effects of drugs. The effectiveness of laser therapy for pain relief, free of side effects, has been reported in painful conditions. METHODS: Two milligrams of each of the above-mentioned crystals was injected in both joints of the back limbs in three groups of rats; these groups were then treated with laser irradiation. Three other groups received no treatment after the injections. We determined the plasmatic levels of inflammatory markers (fibrinogen, prostaglandin E2, and TNF(alpha)), tissues (prostaglandin E(2)) and conducted anatomopathological studies. Twenty-five patients with acute gout arthritis were randomized into two groups and treated over 5 days: group A, diclofenac 75 mg orally, twice a day; and group B, laser irradiation once a day. Forty-nine patients with knee chronic pyrophosphate arthropathy were randomized into two groups and treated over 21 days; group A, diclofenac 50 mg orally, twice a day; and group B, laser irradiation once a day. Thirty patients with shoulder chronic hydroxyapatite arthropathy were randomized into two groups and treated over 21 days; group A, diclofenac 50 mg orally, twice a day; and group B, laser irradiation once a day. RESULTS: Fibrinogen, prostaglandin E(2), and TNF(alpha) concentrations in the rats injected with crystals and treated with laser decreased significantly as compared with the groups injected with crystals without treatment. Both laser therapy and diclofenac achieved rapid pain relief in patients with acute gouty arthritis without significant differences in efficacy. Laser therapy was more effective than diclofenac in patients with chronic pyrophosphate arthropathy and in patients with chronic apatite deposition disease. CONCLUSION: Laser therapy represents an effective treatment in the therapeutic arsenal of microcrystalline arthropathies.

Animals↗
PubMed2005

The Atlantic-Mediterranean transition: discordant genetic patterns in two seabream species, Diplodus puntazzo (Cetti) and Diplodus sargus (L.).

Sparids are a group of demersal perciform fish of high commercial value, which have experienced an extensive radiation, particularly in the Mediterranean, where they occupy a variety of different niches. The present study focuses on two species: Diplodus sargus and D. puntazzo, presenting a wide distribution from the Mediterranean to the eastern Atlantic coasts. They display similar ecological behaviour and are evolutionary closely related. Both are highly appreciated in fisheries and D. puntazzo is currently under domestication process. However, little is know on their population structure and it is an open question whether any genetic differentiation exists at the geographic level. To address this issue we examined sequence variation of a portion of the mitochondrial DNA (mtDNA) control region in population samples of each of the two species collected over a wide geographic range. In addition to the mtDNA, analysis of nuclear loci (allozymes) was included in the study to compare patterns revealed by nuclear and mitochondrial markers. The studied samples covered an area from the eastern Mediterranean to the Portuguese coasts immediately outside the Gibraltar Strait. The two species revealed a level of sequence polymorphism remarkably different for the control region with the D. puntazzo and D. sargus showing 111 and 28 haplotypes, respectively. Such a difference was not detected with allozyme markers. The two species also showed large differences in their population structure. While D. puntazzo presented a marked genetic divergence between the Atlantic and Mediterranean samples, D. sargus showed little intraspecific differentiation. These results were supported using both mtDNA and allozyme markers, and were interpreted as the consequence of differences in the history of the two species such as fluctuations in the effective population size due to bottlenecks and expansions, possibly combined with present-day differences in levels of gene flow.

Animals↗
PubMed2004

Factors associated with inadequate prenatal care in Ecuadorian women.

BACKGROUND: Although inadequate prenatal care has been associated with adverse perinatal outcomes, reports on the factors associated with poor prenatal care in developing Latin American countries are scarce. OBJECTIVE: To determine factors associated with inadequate prenatal care among women from low socioeconomic circumstances. METHOD: Women delivered after a pregnancy duration of more than 20 weeks at the Enrique C. Sotomayor Obstetrics and Gynecology Hospital, Guayaquil, Ecuador, were surveyed. The questionnaire collected sociodemographic data and reasons for having inadequate prenatal care. Adequacy of prenatal care was measured with the Kessner index and correlated to the sociodemographic data. RESULTS: During the study period, 1016 pregnant women were surveyed. Among them, there were adolescents (23.7%), primigravidas (30.8%), and women with a high-risk pregnancy (29.3%). According to the Kessner index, prenatal care was considered adequate or inadequate in 24.5% and 75.5% of cases, respectively. Knowledge regarding the importance of adequate prenatal care and the effects of poor prenatal care was lower among women who had received inadequate prenatal care. The women that were considered to have had adequate prenatal care had at least one visit, and they were more often cared for by a specialist than women who considered having inadequate prenatal care. The three most important reasons associated to inadequate prenatal care in this series (n=767), were economic difficulties having to care for a small child, and transportation difficulties. Logistic regression analysis determined that women with undesired pregnancies who resided in rural areas and were para 5 or higher had an increased risk of inadequate prenatal care. On the other hand, an adverse outcome to a prior pregnancy (abortion, intrauterine fetal demise, or ectopic pregnancy) decreased this risk. Marital status and educational level were confounding factors. CONCLUSIONS: Although prenatal care at our institution is free, adequacy was thought to be low. The main factors associated with poor prenatal care were mostly conditions related to poverty.

Confounding Factors, Epidemiologic↗
PubMed2002

Signals involved in mycobacteria-induced CXCL-8 production by human monocytes.

CXC chemokine-interleukin-8 (IL-8) (CXCL-8) is a potent proinflammatory chemotactic factor that induces important immune responses for antimycobacterial defenses. However, little is known about the biochemical mechanisms by which the mycobacterial antigens upregulate the release of CXCL-8 from human monocytes. In this study, the mechanisms through which Mycobacterium bovis BCG induces CXCL-8 secretion in human monocytes were investigated. We found that M. bovis BCG induced the production of high levels of CXCL-8 by human monocytes. M. bovis-induced CXCL-8 secretion was unaffected by the protein kinase C (PKC) inhibitor bisindolylmaleimide. In contrast, preincubation of the monocytes with the protein tyrosine kinase (PTK) inhibitor genistein resulted in dose-dependent suppression of mycobacteria-induced CXCL-8 secretion. These results were further supported by the fact that treatment of monocytes with herbimycin-A, another well-described inhibitor of PTK activity with a different mechanism of action, significantly diminished the effect of M. bovis on CXCL-8 secretion. In addition, the specificity of this inhibition was demonstrated by the inability of herbimycin-A to block in a significant manner IL-1 beta induction of CXCL-8. Herbimycin-A significantly blocked tyrosine phosphorylation of p59(hck) in response to M. bovis. Finally, two specific NF-kappa B inhibitors, sulfasalazine and caffeic acid phenetyl ester (CAPE), strongly inhibited the production of CXCL-8 by human monocytes infected with M. bovis. These results show intracellular signaling pathways and a transcription factor involved in the M. bovis-mediated upregulation of CXCL-8 biosynthesis and release by human monocytes.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Roles of intracellular calcium and NF-kappaB in the Bacillus Calmette-Guérin-induced secretion of interleukin-8 from human monocytes.

Interleukin (IL)-8 secretion contributes to the early host response against mycobacterial infection by increasing local inflammation and recruiting professional phagocytes. Because the mechanisms through which Mycobacterium bovis Calmette-Guérin (BCG) induces IL-8 secretion are unknown, the aim of the present study was to characterize the nature of IL-8 production induced by BCG in human monocytes. In this study, we found that the induction of IL-8 synthesis was dose- and time-dependent after stimulation with BCG. This IL-8 secretion was not attributed to LPS contamination or the presence of TNF-alpha. We also determined that BCG-induced IL-8 secretion occurs through a mechanism that requires intracellular calcium and likely involves a calmodulin-sensitive step. Interestingly, BCG-induced secretion of IL-8 from human monocytes resulted from transcriptional up-regulation of the IL-8 gene. Moreover, we present evidence that BCG activates nuclear translocation of the transcription factor NF-kappaB, since pretreatment of monocytes with sulfasalazine, a inhibitor of NF-kappaB activity, blocked the ability of BCG to induce IL-8 secretion in a dose-dependent manner, producing 92.5% inhibition at a concentration of 2 mM. These results were further supported by the fact that treatment of cells with curcumin, another well-described inhibitor of NF-kappaB activity with a different mechanism of action, significantly diminished the effect of BCG on IL-8 secretion. Together, these studies are the first to demonstrate that BCG-induced IL-8 secretion by human monocytes appears to be mediated by intracellular Ca(2+) and is NF-kappaB-dependent and at the same time suggest that production of IL-8 in response to M. bovis BCG can contribute to the initial local and systemic inflammatory response in human tuberculosis.

Calcium↗
PubMed2001

Inhibition of Kupffer cells reduced CXC chemokine production and liver injury.

BACKGROUND: Cytokine production is a critical component of ischemia/reperfusion (IR) injury. In the liver, Kupffer cells produce cytokines and chemokines (i.e., cytokines with chemoattractant properties) that are important mediators in neutrophil recruitment and subsequent hepatocellular injury. Therefore, the role of Kupffer cells in chemokine production in hepatic IR injury was investigated. METHODS: Adult male C57BL/6 mice underwent 90 min of partial hepatic ischemia followed by various reperfusion times (i.e., 0, 1.5, 3, and 6 h). Gadolinium chloride (GC), which inhibits Kupffer cell activity, was administered to mice 48 and 24 h prior to ischemia. The control group received a corresponding volume of normal saline. Plasma levels of the cytokine macrophage inflammatory protein-2 (MIP-2), KC, and tumor necrosis factor (TNF)-alpha and liver mRNA were measured. Liver injury was assessed by plasma level of alanine transaminase (ALT) and histopathology. RESULTS: A reperfusion time-dependent liver injury occurred as indicated by increased levels of plasma ALT and histopathology. The injury was associated with increased plasma TNF-alpha, MIP-2, and KC and their hepatic mRNA expression and neutrophil infiltration into ischemic lobes of the liver. GC treatment significantly reduced the number of Kupffer cells as determined by the immunostained liver tissue sections. The extent of liver injury significantly decreased in GC-treated mice that were associated with decreased levels of plasma ALT, TNF-alpha, MIP-2, and KC and neutrophil infiltration. CONCLUSIONS: This study suggests that Kupffer cells are major contributors to cytokine production in hepatic IR and their modulation may serve as a potential target for therapeutic intervention.

Alanine Transaminase↗
PubMed2001

CD8-deficient SJL mice display enhanced susceptibility to Theiler's virus infection and increased demyelinating pathology.

Theiler's murine encephalomyelitis virus (TMEV) infection of the central nervous system (CNS) induces a chronic, progressive demyelinating disease in susceptible mouse strains characterized by inflammatory mononuclear infiltrates and spastic hind limb paralysis. Our lab has previously demonstrated a critical role for TMEV- and myelin-specific CD4(+) T cells in initiating and perpetuating this pathology. It has however, also been shown that the MHC class I loci are associated with susceptibility/resistance to TMEV infection and persistence. For this reason, we investigated the contribution of CD8(+) T cells to the TMEV-induced demyelinating pathology in the highly susceptible SJL/J mouse strain. Here we show that beta2M-deficient SJL mice have similar disease incidence rates to wild-type controls, however beta2M-deficient mice demonstrated earlier onset of clinical disease, elevated in vitro responses to TMEV and myelin proteolipid (PLP) epitopes, and significantly higher levels of CNS demyelination and macrophage infiltration at 50 days post-infection. beta2M-deficient mice also displayed a significant elevation in persisting viral titers, as well as an increase in macrophage-derived pro-inflammatory cytokine mRNA expression in the spinal cord at this same time point. Taken together, these results indicate that CD8(+) T cells are not required for clinical or histologic disease initiation or progression in TMEV-infected SJL mice. Rather, these data stress the critical role of CD4(+) T cells in this capacity and further emphasize the potential for CD8(+) T cells to contribute to protection from TMEV-induced demyelination.

Amino Acid Sequence↗
PubMed2001

Protein tyrosine kinase regulates FAS-mediated apoptosis in human BCG-infected monocytes.

Apoptosis of monocytes/macrophages has emerged as a central regulatory event in the defense against mycobacterial infections. The involvement of protein tyrosine kinases (PTK) in Fas-mediated apoptosis in T cells is well established, but the possible role of PTK in Fas-dependent death of human bacillus Calmette-Guerin (BCG)-infected monocytes remains unclear. Here, we first examined the expression and function of Fas on BCG-infected human monocytes by flow cytometry. The results demonstrated that BCG-infected monocytes expressed significant Fas protein levels. In addition, engagement of the Fas antigen with its agonistic antibody (Ab) resulted in apoptosis of monocytes, as monitored by DNA analysis and fluorescence-activated cell sorter (FACS) analysis. The apoptotic action of Fas was suppressed significantly by genistein, indicating a role for PTK in this death process. Consistent with this observation, herbimycin A and tyrphostin, two selective tyrosine kinase inhibitors with different mechanisms of action, effectively inhibited Fas-mediated apoptosis of BCG-infected monocytes, as demonstrated by DNA content analysis. Moreover, we confirmed the effect of genistein, herbimycin A, and tyrphostin by examining apoptosis with the terminal transferase dUTP nick endlabeling (TUNEL) assay. Collectively, these data demonstrate that Fas-induced apoptosis may represent an important mechanism for eliminating BCG-activated human monocytes and that this apoptosis is due, at least in part, to signaling via a PTK pathway.

Apoptosis↗
PubMed2000

Selenium, zinc and copper plasma levels in intrahepatic cholestasis of pregnancy, in normal pregnancies and in healthy individuals, in Chile.

BACKGROUND/AIMS: Low blood Se levels have been previously shown in normal pregnancies (third trimester) and significantly lower levels in patients with intrahepatic cholestasis of pregnancy (ICP), in Finland and in Chile, suggesting that a low or marginal dietary availability of Se may contribute to the pathogenesis of this disease. The aim of this study was to investigate whether a temporal change in plasma concentration of Se, and seasonal fluctuations in plasma concentrations of Se, Zn and Cu, could coincide with changes in the prevalence of ICP. METHODS: A cross-sectional cohort study was done including 21 ICP patients, 98 women in the third trimester of a normal pregnancy, 29 non-pregnant women, and also 13 individuals (seven non-pregnant women and six men) who had been studied 9 years before. Plasma Se, Zn and Cu were measured by atomic spectroscopy. Plasma Se levels in the present study were compared to the results obtained 5 to 7 years before, employing identical methodology in similar population samples. RESULTS: Plasma Se concentrations in non-pregnant women were higher than in the previous study: 1.43+/-0.34 micromol/l vs 0.85+/-0.13; p<0.001. In comparison to non-pregnant women, normal pregnancies near term had lower plasma levels of Se: 1.08+/-0.25 micromol/l; p<0.01, and Zn: 17.90+/-3.61 micromol/l vs 19.71+/-3.21; p<0.05, but higher plasma levels of Cu: 34.35+/-7.12 micromol/l vs 20.62+/-3.34; p<0.01. In normal pregnancies, plasma Se concentration was significantly higher in summer (1.34+/-0.19 micromol/l) than in the other seasons, while Zn and Cu diminished. Similar to previous studies, ICP patients had significantly lower Se plasma levels than normal pregnancies: 0.94+/-0.12 micromol/l, p<0.05, and Cu levels were significantly higher: 50.80+/-7.02 micromol/l, p<0.01. Cu plasma levels correlated with the biochemical severity of the disease. Zn did not change in ICP. CONCLUSIONS: The present study shows that the decrease in the prevalence of ICP in Chile during the last decade coincides with an increase in plasma Se levels. Its lower incidence during summer coincides with a higher plasma Se concentration in summer than in other seasons, as observed in normal pregnancies.

Adult↗
PubMed1999

Influence of anterodorsal thalamic nuclei on the hypophyseal-adrenal axis and cardiac beta receptors in rats submitted to variable chronic stress.

The limbic structures play an important role in the control of the neuroendocrine and sympathical adrenal function in basal and stress conditions. This work was undertaken to evaluate plasma ACTH, adrenocortical activity, cardiac adrenoceptors density and affinity response to variable chronic stress (VCS) in anterodorsal thalamic nuclei (ADTN) lesioned rats. Thirty days after lesion, shamlesioned stressed animals increased plasma ACTH and corticosterone as compared to sham-lesioned unstressed animals (p < 0.05); lesioned rats increased ACTH levels after VCS (p < 0.05) as compared to unstressed-lesioned rats. Whereas in sham-lesion plasma corticosterone (C) increased after stress, in lesioned animals(C) remained unchanged as compared to unstressed-lesioned animals. In the stressed groups, adrenal C contents were below those found in unstressed rats. beta-receptors affinity, in all the experimental groups, was similar, but VCS sham-lesioned animals underwent a significant increase in cardiac D-adrenergic receptors density when compared with basal and lesioned groups (P < 0.001). Our findings would demonstrate that the increment in cardiac beta adrenoceptors density appears as a consequence of the increase in ACTH, plasma corticosterone and sympathetic response provoked by chronic stress situations. ADTN lesion attenuated this hipophisoadrenal system response to chronic stress as well as the above mentioned cardiac beta adrenoceptors density increment.

Adrenocorticotropic Hormone↗
PubMed1998

Experimental Chagas' disease: effects of propranolol upon cardiac beta-receptors.

Chagas' disease is an important cause of heart disfunction in Latin America. Previous works from our laboratory reproducing experimental Chagas' disease in mice, demonstrated that the affinity and density of cardiac beta-adrenergic receptors were altered during the acute, indeterminate and chronic phase in Albino Swiss mice inoculated with Trypanosoma cruzi. Keeping in mind that Propranolol is a beta-blocking agent that binds in the same receptors' site, which we have described as altered along T. cruzi infection. The present study was performed to determine if a beta-blocker treatment could prevent cardiac beta-receptors' disorders provoked by T. cruzi infection. Two different doses of Propranolol (9 and 40 mg/kg/day) were injected in the mice during 3 days; then they were infected with 7 x 10(4) parasites/mouse and propranolol was continued daily for one week. The results showed that the concentrations of propranolol used did not protect the beta-receptors' sites by administration of each doses.

Acute Disease↗
PubMed1997

Progesterone metabolites and bile acids in serum of patients with intrahepatic cholestasis of pregnancy: effect of ursodeoxycholic acid therapy.

The concentrations in serum of sulfated metabolites of progesterone are known to be elevated in patients with intrahepatic cholestasis of pregnancy (ICP). The profiles of these metabolites and conjugated bile acids were analyzed in serum from 11 patients with ICP before and during administration of ursodeoxycholic acid (UDCA) (8 patients) or placebo (3 patients). The clinical condition of 7 of the patients given UDCA improved markedly, and 1 patient given placebo had a spontaneous remission of the disease. The total concentration of conjugated bile acids in the 11 patients was 25 +/- 6 micromol/L (mean +/- SEM) and decreased to 6.3 +/- 3.5 micromol/L in the 7 patients responding to treatment with UDCA. The level of 7alpha-hydroxy-4-cholesten-3-one was significantly lower (7.2 +/- 2.2 ng/mL) in patients with ICP than in healthy pregnancy (18 +/- 4.6 ng/mL) (P < .05). The concentrations of 5alpha-pregnane-3alpha,20alpha-diol mono- and disulfates decreased by 52% +/- 7.9% and 68% +/- 5.5%, respectively, in the patients responding to treatment. Similar decreases were observed for the mono- and disulfates of 5alpha-pregnane-3alpha,20alpha,21-triol and 5beta-pregnane-3alpha,20alpha-diol. The disulfate of 5alpha-pregnane-3beta,20alpha-diol showed a smaller decrease, while glucuronidated steroids were not affected. The 3alpha-/3beta-hydroxysteroid ratio and di-/monosulfate ratio decreased significantly during UDCA. The magnitudes of the changes of bile acid and steroid concentrations during UDCA were not correlated to each other. The results suggest that UDCA stimulates the biliary excretion of steroids with a 3alpha-sulfoxy group and disulfates. This effect seems to be independent of the effect on bile acid excretion, indicating the use of different transport proteins. The possibility of an effect of UDCA on the formation of the steroid sulfates cannot be excluded.

Bile Acids and Salts↗
PubMed1997

Ursodeoxycholic acid in the treatment of cholestasis of pregnancy: a randomized, double-blind study controlled with placebo.

BACKGROUND/AIMS: Intense pruritus and the risk of stillbirths and premature deliveries justify the search for an effective pharmacologic treatment of intrahepatic cholestasis of pregnancy. This study was designed to test the efficacy of ursodeoxycholic acid in maternal pruritus, the biochemical abnormalities and the outcome of pregnancy, in patients with intrahepatic cholestasis of pregnancy of early onset. METHODS: Pregnant patients hospitalized in a secondary case-referral center with intense pruritus and abnormal serum levels of bile salts and aminotransferases, detected before week 33 of pregnancy, were randomly assigned to receive ursodeoxycholic acid, 1 g per day orally, or an identical placebo, until delivery, in a double-blind study. A 3-week trial period was chosen to compare drug and placebo effects. The follow-up was extended for 3 months after delivery. RESULTS: Twenty-four patients entered the trial; eight had deliveries before 2 weeks of treatment and one dropped out. The study was then completed in 15 patients: eight received ursodeoxycholic acid and seven placebo. No adverse effects were detected in the mothers or in their babies. After 3 weeks of treatment, patients receiving ursodeoxycholic acid (mean daily dose 16 mg/kg body weight) had a significant improvement in pruritus (p<0.02), in serum bilirubin (0.36+/-0.19 mg/dl (mean+/-SD) versus 0.95+/-0.48 in patients receiving placebo, p<0.01), in aspartate aminotransferase (52+/-42 IU/l vs 98+/-44, p<0.05) and in alanine aminotransferase (54+/-50 IU/l vs 229+/-154, p<0.01); serum total bile salts also tended to be lower in patients receiving ursodeoxycholic acid (26.3+/-33.7 micromol/l vs 55.0+/-44.8, p N.S.). Deliveries occurred at or near term in all mothers who received ursodeoxycholic acid (mean week of pregnancy: 38), while they occurred before week 36 of pregnancy in five patients who received placebo, including one stillbirth. All babies born alive had birth weights adequate for gestational age and they were thriving normally 3 months after delivery. CONCLUSIONS: Ursodeoxycholic acid is effective and safe in patients with intrahepatic cholestasis of pregnancy of early onset, attenuating pruritus and correcting some biochemical abnormalities in the mothers. Relevant aspects of fetal outcome were also improved in patients receiving ursodeoxycholic acid compared to placebo.

Adult↗
PubMed1997

Effects of ursodeoxycholic acid on conjugated bile acids and progesterone metabolites in serum and urine of patients with intrahepatic cholestasis of pregnancy.

BACKGROUND/AIMS AND METHODS: The mechanism(s) behind the effects of ursodeoxycholic acid on serum steroid sulphate profiles in patients with intrahepatic cholestasis of pregnancy is not clear. Conjugated progesterone metabolites and bile acids have therefore been analysed in serum and urine of patients with intrahepatic cholestasis of pregnancy before and during treatment with ursodeoxycholic acid using chromatographic and mass spectrometric methods. RESULTS: The concentration of glycine-/taurine-conjugated bile acids decreased from 8.9+/-3 micromol/l (mean+/-SEM) before treatment to 1.8+/-0.6 micromol/l during treatment with ursodeoxycholic acid. The total bile acid excretion in urine decreased from 56+/-14 to 32+/-5.6 micromol/g creatinine. The proportion of cholic acid in serum and urine, and of 1beta-, 2beta- and 6alpha-hydroxylated cholic acids in urine decreased markedly during ursodeoxycholic acid while the percentages of 3alpha,12alpha-dihydroxy-3-oxo-4-cholenoic acid and chenodeoxycholic acid were unchanged. The levels in serum and excretion in urine of sulphated steroids decreased during ursodeoxycholic acid, by 45-49% for disulphates and 33-35% for monosulphates. The ratios of 3alpha- to 3beta-hydroxysteroid disulphates were lowered by ursodeoxycholic acid from 1.1 (mean) to 0.68 in serum, and from 1.2 to 0.70 in urine. The corresponding ratios for monosulphates before and during ursodeoxycholic acid were 6.9 and 4.5, respectively, in serum, and 21 and 5.2, respectively, in urine. The major monosulphates in urine, dominated by 5alpha-pregnane-3alpha, 20alpha-diol, were also conjugated with N-acetylglucosamine. The excretion of these double conjugates decreased from 27+/-8.4 to 15+/-5.3 micromol/g creatinine during ursodeoxycholic acid. In contrast to sulphated steroids, the concentrations of glucuronides were unchanged in serum and their excretion in urine tended to increase during ursodeoxycholic acid. The metabolism of ursodeoxycholic acid was similar to that described in nonpregnant subjects. In addition to metabolites hydroxylated in the 1beta-, 5beta-, 6alpha/beta and 22-positions, a 4-hydroxy-ursodeoxycholic acid was tentatively identified. This occurred predominantly as a double conjugate with glycine/taurine and glucuronic acid, as did other 4-hydroxylated bile acids of probable foetal origin. CONCLUSIONS: The results are compatible with the contention that ursodeoxycholic acid stimulates the biliary excretion of sulphated progesterone metabolites, particularly those with a 3alpha-hydroxy-5alpha(H) configuration and disulphates. The effect(s) appears to be independent of the stimulation of bile acid secretion. An effect of ursodeoxycholic acid on the reductive metabolism of progesterone cannot be excluded.

Bile Acids and Salts↗
PubMed1997

Profiles of bile acids and progesterone metabolites in the urine and serum of women with intrahepatic cholestasis of pregnancy.

BACKGROUND/AIMS AND METHODS: The etiology of intrahepatic cholestasis of pregnancy (JCP) is unknown. We have performed comprehensive chromatographic and mass spectrometric analyses of progesterone metabolites and bile acids in serum and urine of six patients in order to characterize changes that might be of importance for the development of the disease. RESULTS: Conjugated bile acids were increased in serum and urine of patients with ICP while the levels of unconjugated bile acids were similar in healthy pregnancies and ICP. Unconjugated and conjugated 7 alpha, 12 alpha-dihydroxy-3-oxo-4-cholenoic acid was excreted in urine both in healthy pregnancies and in ICP, possibly indicating a rate limitation of 3-oxo-delta 4-steroid 5 beta-reductase in pregnancy. The serum levels and urinary excretion of total sulfated progesterone metabolites were increased in ICP while the glucuronides were unchanged or low. Confirming previous results, the fraction of metabolites with 3 alpha-hydroxy-5 alpha(H) configuration was increased. The urinary excretion of 5 alpha-pregnane-3 alpha, 20 alpha-diol 3-sulfate, 20-N-acetylglucosaminide was greatly increased in ICP, as was that of 3 alpha-hydroxy-5 alpha-androstane-17 beta-carboxylic acid, assumed to be a progesterone metabolite. CONCLUSIONS: The combined results of this and previous studies are compatible with a primary change in the reductive metabolism of progesterone in ICP, resulting in increased formation of metabolites with a 3 alpha-hydroxy-5 alpha(H) configuration and a larger fraction of sulfates. There also seems to be a selective defect in the biliary secretion of sulfated metabolites, particularly disulfates.

Bile Acids and Salts↗
PubMed1995

Peripheral blood T lymphocytes in seasonal bronchial asthma.

Variations in T lymphocytes in asthmatic patients are related to disease severity. However, the effects of natural exposure to pollens on peripheral blood T lymphocytes have not been clarified. In this paper, the effects on peripheral blood CD4 and CD8 lymphocytes from pollen-sensitive subjects and from nonatopic donors were studied during and outside the pollen season. In patients who suffer from seasonal asthma, we found an increase in the CD4/CD8 bright ratio and a decrease in the mean number of CD4 receptors per cell during the pollen season. No variation was observed in healthy subjects. These results suggest that CD4 lymphocytes may be causally linked to the pathogenesis of seasonal bronchial asthma.

Adolescent↗
PubMed1995

[Can a selenium deficiency affect the pathogenesis of cholestasis in pregnancy?].

UNLABELLED: In search of an environmental factor which modulates the expressivity of cholestasis of pregnancy and explains the seasonal and annual variations observed in Finland and Chile, the authors measured selenium (Se) concentration in the plasma and erythrocytes by atomic absorption spectrophotometry and the activity of the glutation peroxidase enzyme dependent on Se (GSH-Px) by a spectrophotometric method in 10 patients with cholestasis of pregnancy, 22 normal pregnant women, 43 non pregnant women and in 15 men, all of whom had normal weight/height, and similar ages, ethnic and geographic origin. Blood samples were obtained weekly from the pregnant women during the third trimester and 24-72 hours postpartum. RESULTS: In non pregnant women and in men plasma Se was 0.83 +/- 0.02 mumol/l (range 0.6-1.2) and the GSH-Px activity was 306 +/- 5 U/L (range 203-459). Both parameters were correlated and were similar to those of other populations whose ingestion of Se is low (Finland, New Zealand, and certain regions of China). In normal pregnant women studied between weeks 20 and 32, the plasma Se and GSH-Px activity were lower than in non pregnant women (0.71 +/- 0.02 mumol/l and 260 +/- 5 U/l, respectively) with both progressively decreasing at the end of pregnancy and rapidly recovering post partum. The erythrocytic GSH-Px activity was similar in normal pregnant women than in non pregnant women (27.7 +/- 0.8 versus 28.1 +/- 0.6 U/g Hb). In patients with cholestasis of pregnancy, plasma and erythrocytic Se and GSH-Px activity were lower than in normal pregnant women (p < 0.05 in similar stages of pregnancy).(ABSTRACT TRUNCATED AT 250 WORDS)

Chile↗