[Superficial scars and hydrocolloids].
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Administration, Topical↗
Biomedical subjects
J Perez
Publications and source records attributed to J Perez.
Somatostatin increases glucocorticoid binding and signaling in macrophages by blocking the calpain-specific cleavage of Hsp 90.
Somatostatin has direct anti-inflammatory actions and participates in the anti-inflammatory actions of glucocorticoids, but the mechanisms underlying this regulation remain poorly understood. The objective of this study was to evaluate whether somatostatin increases glucocorticoid responsiveness by up-regulating glucocorticoid receptor (GR) expression and signaling. Somatostatin promoted a time- and dose-dependent increase in [(3)H]dexamethasone binding to RAW 264.7 macrophages. Cell exposure to 10 nM somatostatin for 18 h promoted a 2-fold increase in the number of GR sites per cell without significant modification of the affinity. Analysis of GR heterocomplex components demonstrated that somatostatin increased the level of heat shock protein (Hsp) 90, whereas the level of GR remained almost unchanged. The increase in Hsp 90 was associated with a decrease in the cleavage of its carboxyl-terminal domain. Evidence for the involvement of calpain inhibition in this process was obtained by the demonstration that 1) somatostatin induced a dose-dependent decrease in calpain activity and 2) calpain inhibitors, calpain inhibitor I and calpeptin, both abolished the cleavage of Hsp 90 and induced a dose-dependent increase in [(3)H]dexamethasone binding. Increases in glucocorticoid binding after somatostatin treatment were associated with similar increases in the ability of GR to transactivate a minimal promoter containing two glucocorticoid response elements (GRE) and to interfere with the activation of nuclear factor-kappaB (NF-kappaB). Thus, the present findings indicate that somatostatin increases glucocorticoid binding and signaling by limiting the calpain-specific cleavage of GR-associated Hsp 90. This mechanism may represent a novel target for intervention to increase glucocorticoid responsiveness.
Animals↗
Monitoring gamma-aminobutyric acid in human brain and plasma microdialysates using micellar electrokinetic chromatography and laser-induced fluorescence detection.
Due to its low electrophoretic mobility, few studies have been able to measure gamma aminobutyric acid (GABA) in biological samples by means of capillary zone electrophoresis. Nevertheless, in micellar electrokinetic chromatography (MEKC) by adding a surfactant to the mobile phase separation can be carried out on the basis of the partition coefficient of the molecules rather than their electrophoretic mobility. In the present study microdialysis coupled to MEKC with laser induced fluorescence detection was used to successfully monitor GABA from cerebrospinal fluid and plasma dialysates. Moreover, we monitored changes in extracellular GABA from a human brain. Microdialysis samples were collected from a Parkinson's disease patient undergoing a thallamotomy as part of her treatment. Significant decreases in extracellular GABA were detected during high frequency electrical stimulation and following a thermolesion of the thalamus. These results demonstrate the feasibility of MEKC coupled to laser-induced fluorescence detection in resolving neutral amino acids, specifically GABA, from different human body fluids.
Brain↗
Rhes: A striatal-specific Ras homolog related to Dexras1.
We have characterized an apparently full-length cDNA corresponding to a rat mRNA, SE6C, previously identified by subtractive hybridization as being expressed predominantly in the striatal region of the brain. The SE6C mRNA encodes a 266 amino acid protein with significant similarity to members of the Ras-like GTP-binding protein family; thus, we have chosen the name Rhes, for Ras homolog enriched in striatum. The human homolog was found in a genomic sequence from human chromosome 22q13.1 and shares 95% identity with rat Rhes. Among the family of small G-proteins, Rhes shares 62% identity with Dexras1, a mouse dexamethasone-inducible Ras-like protein. Both Rhes and Dexras1 have substantially longer C-termini than other members of the Ras-like small G-protein family. Divergence between the C-terminal sequences of Rhes and Dexras1 suggests that, although their functions are probably similar, they have unique properties. Bacterially expressed Rhes binds GTP, suggesting that the protein indeed has GTPase functionality. Although Rhes was not induced by dexamethasone, its full expression is dependent upon thyroid hormone availability. Its accumulation is postnatal, consistent with the dependence upon thyroid hormone. It is noteworthy that most striatum-"specific" mRNAs characterized to date encode components of signal transduction cascades.
Amino Acid Sequence↗
Abnormalities of cyclic adenosine monophosphate signaling in platelets from untreated patients with bipolar disorder.
BACKGROUND: Abnormalities in the cyclic adenosine monophosphate (cAMP)-dependent phosphorylation system have been recently reported in patients with bipolar disorder. We evaluated the immunoreactivity of the regulatory and catalytic subunits of cAMP-dependent protein kinase (protein kinase A) and 1 of its substrates, Rap1, in platelets from untreated euthymic, manic, and depressed patients with bipolar disorder and healthy subjects. METHODS: Platelets were collected from 112 drug-free patients with bipolar disorder (52 euthymic, 29 depressed, and 31 manic) and 62 healthy subjects. The levels of cAMP-dependent protein kinase and Rap1 were assessed by Western blot analysis, immunostaining, and computer-assisted imaging. RESULTS: The immunolabeling of the catalytic subunit of cAMP-dependent protein kinase was significantly different among groups (P<.001), with higher values in untreated depressed and manic patients with bipolar disorder compared with untreated euthymic patients with bipolar disorder and healthy subjects. No significant differences were found in the immunolabeling of the regulatory subunits (type I and type II) of cAMP-dependent protein kinase. The immunolabeling of Rap1 was significantly higher (P<.001) in untreated euthymic, depressed, and manic patients than in healthy persons. CONCLUSIONS: Levels of Rap1 and the catalytic subunit of cAMP-dependent protein kinase are altered in the platelets of bipolar patients. These findings may provide clues toward understanding the involvement of cAMP signaling in the pathogenesis of bipolar disorder.
Adult↗
Reduction of tumour necrosis factor alpha expression and signalling in peripheral blood mononuclear cells from patients with thalassaemia or sickle cell anaemia upon treatment with desferrioxamine.
Recent evidence indicates that the rate of progression of the HIV-1 disease is significantly reduced in thalassaemia major patients upon treatment with high doses of desferrioxamine (DFX). The authors have previously demonstrated that in vitro exposure of mononuclear cells to DFX decreases the bioavailability of tumour necrosis factor alpha (TNF-alpha) which has a stimulatory effect on HIV-1 replication. In this study, therefore, TNF-alpha bioavailability from mononuclear cells isolated from 10 patients with thalassaemia or sickle cell anaemia given DFX as compared to 10 untreated subjects has been evaluated. Evidence is presented showing that DFX treatment reduces TNF-alpha bioavailability (P<0.05) by inhibiting its steady state (P<0.05) and by enhancing its inactivation through binding to soluble TNF-alpha receptor type II (P<0.05). We also show that DFX treatment limits the in vivo activation of NF-kappaB, a transcription factor involved in both TNF-alpha gene transcription and TNF-alpha signalling (P<0.005). We conclude that TNF-alpha bioavailability and signalling are impaired in patients upon DFX treatment. This mechanism may contribute to delayed progression of the HIV-1 infection in vivo.
Adolescent↗
Immunization with Escherichia coli-produced soluble MHC class I proteins induces accelerated rejection or prolonged survival of rat cardiac allografts.
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Animals↗
Use of heliox-driven nebulizer therapy in the treatment of acute asthma.
STUDY OBJECTIVE: To compare the effectiveness of a helium-oxygen mixture with that of oxygen alone as an aerosolizing gas for beta-agonist therapy in patients with mild to moderate exacerbation of asthma. METHODS: A prospective, single-blinded study was performed in an urban teaching hospital over a period of 5 months. A convenience sample of 205 patients with mild to moderate exacerbation of asthma were enrolled. The participants were randomly assigned to 1 of 2 groups. The first group received 3 doses of albuterol, 5.0 mg aerosolized in 10 L/min of oxygen, 15 minutes apart. The second group received 3 doses of albuterol, 5.0 mg aerosolized in 10 L/min of a 70:30 helium-oxygen mixture (heliox), 15 minutes apart. Peak expiratory flow rate (PEFR), forced vital capacity (FVC), and forced expiratory volume in 1 second (FEV1 ) were measured before and after each treatment. Only PEFR and FEV1 were used in data analysis. RESULTS: Although both the heliox and the oxygen group showed significant improvement in PEFR from baseline after 45 minutes (72% and 70%, respectively), the difference between the 2 groups was clinically and statistically insignificant (P =.56). Similar findings were observed for FEV1. There was no difference in rate of admission or rate of complications between the 2 groups. CONCLUSION: Despite its ability to decrease the turbulent flow in airways and to reach distal pulmonary tissues, heliox had no clinically significant advantage over standard therapy in the treatment of mild to moderate asthma. Further large-scale studies are necessary to determine the clinical efficacy of heliox in this setting.
Adolescent↗
Cloning and physical mapping of Atlantic salmon (Salmo salar L.) telomeric sequences.
We cloned and sequenced DNA containing telomeric sequences from Atlantic salmon (Salmo salar L.). At both low and high stringency conditions, a cloned probe containing (TTAGGG)n sequences binds only at the extreme termini of the chromosomes, not at interstitial sites. Blocks of interstitial telomere-like sequences were expected from the chromosome polymorphism because of Robertsonian translocations that exist in Atlantic salmon. Our results support the hypothesis that telomeric sequences were almost entirely lost during chromosome fusion events.
Animals↗
Physical distribution of SINE elements in the chromosomes of Atlantic salmon and rainbow trout.
SINE sequences are interspersed throughout virtually all eukaryotic genomes. In the family Salmonidae three families of SINEs have been identified. In this work we have attempted to characterize and locate by means of fluorescent in situ hybridization (FISH) one of these families (HpaI) in the genome of Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss). Our results show that these SINEs are interspersed throughout all the chromosome pairs except for the heterochromatin-positive areas, generating a banding pattern that could be useful for chromosome identification in both species.
Animals↗
Enteropathogens and other factors associated with severe disease in children with acute watery diarrhea in Lima, Peru.
To evaluate enteropathogens and other factors associated with severe disease in children with diarrhea, 381 children <5 years of age with diarrhea and moderate to severe dehydration (in-patients) and 381 age-, sex-, and date-of-visit-matched children with mild diarrhea (out-patients) presenting to a hospital in Peru, were studied. Rotavirus was detected in 52% of the in-patients and 35% of the out-patients (odds ratio [OR]=2.3, 95% confidence interval [95% CI]= 1.6-3.2); 95% of the rotaviruses among in-patients were of serotypes G1-G4. The risk of severe diarrhea was particularly great in children who were not exclusively breast-fed in early infancy and who also lacked piped water in their homes (for children with both characteristics OR=6.8, 95% CI=3.6-12.8). The high prevalence of rotavirus and its association with severe diarrhea underscores the need for rotavirus vaccines. Interventions to educate mothers and improve access to safe water should augment the impact of rotavirus vaccines in preventing severe diarrhea.
Animals↗
Acute and nongenomic effects of testosterone on isolated and perfused rat heart.
Gonadal steroid hormones influence vascular tone and the development of hypertension. There are sex differences in the incidence of cardiovascular diseases, and great attention has been placed on the study of estrogen cardiovascular effects. However, there are only a few reports on the effects of testosterone on the vasculature. It is commonly accepted that the mechanism of the action of steroid hormones on target tissues is mediated through the binding of hormones to cytoplasmic or nuclear receptors. However, some studies indicate that steroid action can be extremely rapid and therefore unlikely to be through a genomic mechanism. The purpose of this study was to assess the effect of intravascularly confined testosterone on an isolated rat heart to demonstrate acute and possibly nongenomic effects of the steroid. Our results show that testosterone blocked the adenosine vasodilator effect and increased vascular resistance, even when its presence was restricted to the coronary vascular lumen. These effects were exerted rapidly and possibly through nongenomic mechanisms.
Adenosine↗
Thermodynamics of a two-dimensional unbounded self-gravitating system.
The thermodynamics of a two-dimensional self-gravitating system occupying the whole plane is considered in the mean-field approximation. First, it is proven that, if the number N of particles and the total energy E are imposed as the only external constraints, then the entropy admits the least upper bound S+(N,E)=2E/N+N ln(epi(2)) (in appropriate units). Moreover, there does exist a unique state of maximum entropy, which is characterized by a Maxwellian distribution function with a temperature T=N/2 independent of E. Next, it is shown that, if the total angular momentum J is imposed as a further constraint, the largest possible value of the entropy does not change, and there is no admissible state of maximum entropy, but in the case J=0. Finally, some inequalities satisfied by a class of so-called H functions and related generalized entropies are given.
Journal Article↗
Stiripentol: efficacy and tolerability in children with epilepsy.
PURPOSE: Stiripentol (STP) is a new antiepileptic drug (AED) that inhibits cytochrome P450, resulting in increased plasma concentrations of concomitant AEDs. The efficacy and tolerability of STP as an add-on therapy in children were assessed. METHODS: Two hundred twelve patients with refractory epilepsy, aged from 1 month to 20.5 years, received STP either in a single-blind, placebo-controlled trial (108 patients) or in a further open trial (104 other patients selected by epilepsy syndrome for possible efficacy based on the results of the previous trial). RESULTS: Among the 97 patients who could be analyzed for efficacy in the placebo-controlled study, the median seizure frequency was lower at 3 months with STP than with the placebo (p<0.0001); 49% responded to the drug, including 10% who became seizure free. Patients with partial epilepsy had the highest response rate (57%). Results were confirmed in the open study where 68% of the 91 patients receiving STP responded at 3 months. These patients were mainly those with partial epilepsy (73%) who were receiving carbamazepine (CBZ) (75%) as comedication (p<0.001). Ten of the 20 children with severe myoclonic epilepsy in infancy also responded with clobazam (CLB) as comedication. Efficacy was sustained long term in 74% of the 94 patients still receiving STP at a mean 30-month follow-up. Adverse events were reported in 48% of the 212 patients, mainly anorexia and loss of weight, but these events required STP discontinuation in only nine cases. Side effects were minimized in the open trial by optimizing the dose of comedication. CONCLUSIONS: STP seems to be a promising add-on drug, particularly when combined with CBZ in patients with partial childhood epilepsy refractory to vigabatrin (VGB) and with CLB in patients with severe myoclonic epilepsy in infancy.
Adolescent↗
Screening of tuberculosis: is it a real prediction model?
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Cost-Benefit Analysis↗
Safety, immunogenicity, and lot stability of the whole cell/recombinant B subunit (WC/rCTB) cholera vaccine in Peruvian adults and children.
To assess the safety, immunogenicity, and lot stability of the whole cell/recombinant B subunit cholera vaccine, 2 lots manufactured in June 1991 and February 1992 were tested in January 1995. Two oral doses of vaccine or placebo given 2 weeks apart were given with buffer to 216 Peruvian adults and children. Symptoms were elicited for 3 days after each dose. Serum and plasma specimens obtained from each volunteer before vaccination and 10-14 days after the second dose were tested for vibriocidal and anti-cholera toxin antibodies. The vaccine was well-tolerated. Nearly half of the 100 vaccinees had pre-vaccination vibriocidal titers > or = 1:40. Elevated titers were observed in 22% of 37 children 2-5 years of age compared with 66% of 63 vaccinees 6-65 years (P < 0.001). A > or =2-fold serum vibriocidal response was observed in 55% of 100 vaccinees and 6% of 32 placebo recipients. An elevated pre-vaccination titer (< or =1:40) did not change the proportion of vaccinees who responded with a > or =2-fold increase in vibriocidal titer (51% versus 59%, difference not significant), but did change the proportion responding with a > or =4-fold increase (41% versus 22%; P < 0.05). The vibriocidal seroconversion rate was lowest in children 2-5 years old despite low pre-vaccination titers. Two-fold or greater serum antitoxic responses in IgA and IgG were observed in >90% of the vaccinees; > or =4-fold responses were seen in 65-70% of the vaccinees with a 6-8-fold increase over baseline. Plasma specimens were as good as sera for determining anti-toxic antibodies by ELISA, but were less satisfactory for determining vibriocidal antibody titers.
Administration, Oral↗
Laser hair removal: where are we now?
The hair removal market is evolving rapidly. The goal has always been long-term epilation. Success is dependent on understanding hair biology and physiology and on knowledge of laser physics, skin optics, and tissue preservation with respect to these emerging laser technologies. These topics will be reviewed, as will specific categories of laser systems in the hair removal arena and the clinical aspects of laser hair removal today.
Electrolysis↗
Low environmental pH is responsible for the induction of nitric-oxide synthase in macrophages. Evidence for involvement of nuclear factor-kappaB activation.
Stimulation of macrophages with endotoxin and/or cytokines is responsible for the expression of the inducible isoform of nitric oxide synthase (iNOS). Because macrophages are exposed to low pH within the microenvironment of inflammatory lesions, the potential role of acidic pH as an additional regulator of iNOS was investigated. Substitution of the culture medium of rat peritoneal macrophages at pH 7.4 with medium at pH 7.0 up-regulated iNOS activity, as reflected by a 2.5-fold increase in nitrite accumulation. The increase in iNOS activity was associated with a similar increase in iNOS mRNA expression that reflected an increase in iNOS mRNA synthesis rather than stability. Low environmental pH-induced iNOS gene transcription involved the activation of nuclear factor-kappaB (NF-kappaB) transcription factor since exposure of macrophages to low environmental pH both increased NF-kappaB binding activity in the nucleus and enhanced NF-kappaB-driven reporter gene expression. In addition, treatment of macrophages with pyrrolidine dithiocarbamate or n-acetyl-leucinyl-leucinyl-norleucinal, two drugs preventing NF-kappaB translocation to the nucleus, canceled low pH-induced nitrite accumulation. The overall mechanism required the synthesis of tumor necrosis factor alpha (TNFalpha). Indeed, 1) elevated TNFalpha bioactivity was observed in the medium of macrophages exposed to pH 7.0, and 2) incubation of macrophages with a neutralizing anti-TNFalpha antibody impaired both NF-kappaB activation and nitrite accumulation in response to acid challenge. In summary, exposure of macrophages to acidic microenvironment in inflammatory lesions leads to the up-regulation of iNOS activity through the activation of NF-kappaB.
Acids↗