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1.
Microbiol Spectr ; 12(7): e0351323, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38785434

ABSTRACT

Sweet orange (Citrus sinensis) is one of the most important fruit crops worldwide. Virus infections in this crop can interfere with cellular processes, causing dramatic economic losses. By performing RT-qPCR analyses, we demonstrated that citrus psorosis virus (CPsV)-infected orange plants exhibited higher levels of unprocessed microRNA (miRNA) precursors than healthy plants. This result correlated with the reported reduction of mature miRNAs species. The protein 24K, the CPsV suppressor of RNA silencing (VSR), interacts with miRNA precursors in vivo. Thus, this protein becomes a candidate responsible for the increased accumulation of unprocessed miRNAs. We analyzed 24K RNA-binding and protein-protein interaction domains and described patterns of its subcellular localization. We also showed that 24K colocalizes within nuclear D-bodies with the miRNA biogenesis proteins DICER-LIKE 1 (DCL1), HYPONASTIC LEAVES 1 (HYL1), and SERRATE (SE). According to the results of bimolecular fluorescence complementation and co-immunoprecipitation assays, the 24K protein interacts with HYL1 and SE. Thus, 24K may inhibit miRNA processing in CPsV-infected citrus plants by direct interaction with the miRNA processing complex. This work contributes to the understanding of how a virus can alter the regulatory mechanisms of the host, particularly miRNA biogenesis and function.IMPORTANCESweet oranges can suffer from disease symptoms induced by virus infections, thus resulting in drastic economic losses. In sweet orange plants, CPsV alters the accumulation of some precursors from the regulatory molecules called miRNAs. This alteration leads to a decreased level of mature miRNA species. This misregulation may be due to a direct association of one of the viral proteins (24K) with miRNA precursors. On the other hand, 24K may act with components of the cell miRNA processing machinery through a series of predicted RNA-binding and protein-protein interaction domains.


Subject(s)
Citrus sinensis , MicroRNAs , Plant Diseases , Viral Proteins , MicroRNAs/metabolism , MicroRNAs/genetics , Plant Diseases/virology , Viral Proteins/metabolism , Viral Proteins/genetics , Citrus sinensis/virology , Citrus sinensis/metabolism , Plant Viruses/genetics , Plant Viruses/metabolism , Plant Viruses/physiology , Plant Proteins/metabolism , Plant Proteins/genetics , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , RNA Processing, Post-Transcriptional , Citrus/virology , Citrus/metabolism , RNA Precursors/metabolism , RNA Precursors/genetics
2.
J Clin Rheumatol ; 29(5): e59-e70, 2023 Aug 01.
Article in English | MEDLINE | ID: mdl-37005371

ABSTRACT

OBJECTIVE: The aim of this study was to provide an evidence-based framework to guide health care professionals treating patients under glucocorticoid (GC) therapy and develop guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis (GIO) in postmenopausal women and men aged ≥50 years. METHODS: An expert panel on bone diseases designed a series of clinically meaningful questions following the PICO (Population, Intervention, Comparator, and Outcome) structure. Using GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology, we made a systematic literature review, extracted and summarized the effect estimates, and graded the quality of the evidence. The expert panel voted each PICO question and made recommendations after reaching an agreement of at least 70%. RESULTS: Seventeen recommendations (9 strong and 8 conditional) and 8 general principles were developed for postmenopausal women and men aged ≥50 years under GC treatment. Bone mineral density (BMD), occurrence of fragility fractures, probability of fracture at 10 years by Fracture Risk Assessment Tool, and other screening factors for low BMD are recommended for patient evaluation and stratification according to fragility fracture risk. The treatment of patients under GC therapy should include counseling on lifestyle habits and strict control of comorbidities. The goal of GIO treatment is the nonoccurrence of new fragility fractures as well as to increase or maintain BMD in certain clinical situations. This was considered for the therapeutic approach in different clinical scenarios. CONCLUSIONS: This GIO guideline provides evidence-based guidance for health care providers treating patients.


Subject(s)
Glucocorticoids , Osteoporosis , Male , Humans , Female , Middle Aged , Aged , Glucocorticoids/therapeutic use , Postmenopause , Osteoporosis/chemically induced , Osteoporosis/diagnosis , Osteoporosis/drug therapy , Bone Density
3.
Arch Virol ; 166(6): 1533-1545, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33683476

ABSTRACT

Beekeeping is a widespread activity in Argentina, mainly producing honey that has gained both national and international recognition. There are more than 3,000,000 hives in the country, mainly concentrated in Buenos Aires Province (approximately 1,000,000 hives). In recent decades, worrying rates of hive loss have been observed in many countries around the world. In Latin America, the estimated loss of hives is between 13% (Peru and Ecuador) and 53% (Chile). Argentina had annual losses of 34% for the period of October 1, 2016 to October 1, 2017. The causes of these losses are not clear but probably involve multiple stressors that can act simultaneously. One of the main causes of loss of bee colonies worldwide is infestation by the ectoparasitic mite Varroa destructor in combination with viral infections. To date, 10 viruses have been detected that affect honey bees (Apis mellifera) in Argentina. Of these, deformed wing virus, sacbrood virus, acute bee paralysis virus, chronic bee paralysis virus, and Israeli acute bee paralysis can be transmitted by mites. Deformed wing virus and the AIK complex are the viruses most often associated with loss of hives worldwide. Considering that bee viruses have been detected in Argentina in several hymenopteran and non-hymenopteran insects, these hosts could act as important natural reservoirs for viruses and play an important role in their dispersal in the environment. Further studies to investigate the different mechanisms by which viruses spread in the environment will enable us to develop various strategies for the control of infected colonies and the spread of viruses in the habitat where they are found.


Subject(s)
Bees/virology , Animals , Argentina , DNA Viruses/genetics , DNA Viruses/isolation & purification , Host-Pathogen Interactions , RNA Viruses/genetics , RNA Viruses/isolation & purification
4.
Planta ; 251(1): 7, 2019 Nov 27.
Article in English | MEDLINE | ID: mdl-31776669

ABSTRACT

MAIN CONCLUSION: miRNA targets from Citrus sinensis are predicted and validated using degradome data. They show an up-regulation upon infection with CPsV, with a positive correlation between target expression and symptom severity. Sweet orange (Citrus sinensis) may suffer from disease symptoms induced by virus infections, thus resulting in drastic economic losses. Infection of sweet orange plants with two isolates of citrus psorosis virus (CPsV), expressing different symptomatologies, alters the accumulation of a set of endogenous microRNAs (miRNAs). Here, we predicted ten putative targets from four down-regulated miRNAs: three belonging to the CCAAT-binding transcription factor family (CBFAs); an Ethylene-responsive transcription factor (RAP2-7); an Integrase-type DNA-binding superfamily protein (AP2B); Transport inhibitor response 1 (TIR1); GRR1-like protein 1-related (GRR1); Argonaute 2-related (AGO2), Argonaute 7 (AGO7), and a long non-coding RNA (ncRNA). We validated six of them through analysis of leaf degradome data. Expressions of the validated targets increase in infected samples compared to healthy tissue, showing a more striking up-regulation those samples with higher symptom severity. This study contributes to the understanding of the miRNA-mediated regulation of important transcripts in Citrus sinensis through target validation and shed light in the manner a virus can alter host regulatory mechanisms leading to symptom expression.


Subject(s)
Citrus sinensis/metabolism , Citrus sinensis/virology , MicroRNAs/metabolism , Plant Viruses/pathogenicity , Transcriptional Activation/genetics , Transcriptional Activation/physiology
5.
Arch Argent Pediatr ; 115(6): e404-e411, 2017 Dec 01.
Article in English, Spanish | MEDLINE | ID: mdl-29087123

ABSTRACT

Alopecia areata (AA) is a dermatological disease characterized by non-scarring hair loss of the scalp and/or body, with an unpredictable and variable evolution in the patients in which, despite multidisciplinary efforts, its etiology is not entirely known, although some evidence suggests that environmental, immunological and genetic factors could be generating the disease. The aim of this review is to provide an updated panorama of the clinical characteristics, diagnosis and treatment of AA, to analyze the mechanisms that could participate in its etiology, as well as to review some of the most important genetic variants that could confer susceptibility to the development of this disease.


La alopecia areata es un padecimiento dermatológico caracterizado por la pérdida de pelo no cicatricial del cuero cabelludo y/o del cuerpo, con una evolución impredecible y variable en los pacientes. A pesar de esfuerzos multidisciplinarios, su etiología sigue sin conocerse con exactitud, aunque algunas evidencias sugieren que factores ambientales, inmunológicos y genéticos podrían estar originando la enfermedad. El objetivo de esta revisión consiste en dar un panorama actual de las características clínicas, diagnóstico y tratamiento de la alopecia areata, analizar los mecanismos que podrían participar en su etiología, así como revisar algunas de las variantes génicas más importantes, que podrían conferir susceptibilidad al desarrollo de la enfermedad.


Subject(s)
Alopecia Areata , Adolescent , Alopecia Areata/diagnosis , Alopecia Areata/epidemiology , Alopecia Areata/etiology , Alopecia Areata/therapy , Child , Child, Preschool , Female , Humans , Male , Prognosis
6.
Mol Plant Pathol ; 17(3): 317-29, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26033697

ABSTRACT

Sweet orange (Citrus sinensis), one of the most important fruit crops worldwide, may suffer from disease symptoms induced by virus infections, thus resulting in dramatic economic losses. Here, we show that the infection of sweet orange plants with two isolates of Citrus psorosis virus (CPsV) expressing different symptomatology alters the accumulation of a set of endogenous microRNAs (miRNAs). Within these miRNAs, miR156, miR167 and miR171 were the most down-regulated, with almost a three-fold reduction in infected samples. This down-regulation led to a concomitant up-regulation of some of their targets, such as Squamosa promoter-binding protein-like 9 and 13, as well as Scarecrow-like 6. The processing of miRNA precursors, pre-miR156 and pre-miR171, in sweet orange seems to be affected by the virus. For instance, virus infection increases the level of unprocessed precursors, which is accompanied by a concomitant decrease in mature species accumulation. miR156a primary transcript accumulation remained unaltered, thus strongly suggesting a processing deregulation for this transcript. The co-immunoprecipitation of viral 24K protein with pre-miR156a or pre-miR171a suggests that the alteration in the processing of these precursors might be caused by a direct or indirect interaction with this particular viral protein. This result is also consistent with the nuclear localization of both miRNA precursors and the CPsV 24K protein. This study contributes to the understanding of the manner in which a virus can alter host regulatory mechanisms, particularly miRNA biogenesis and target expression.


Subject(s)
Citrus/virology , Gene Expression Regulation, Viral , MicroRNAs/genetics , Plant Viruses/genetics , RNA Precursors/genetics , RNA Processing, Post-Transcriptional/genetics , Viral Proteins/metabolism , Conserved Sequence/genetics , Green Fluorescent Proteins/metabolism , Immunoprecipitation , MicroRNAs/metabolism , Plant Diseases/virology , Plants, Genetically Modified , Protein Binding , RNA Precursors/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Nicotiana/genetics
7.
PLoS One ; 10(11): e0143131, 2015.
Article in English | MEDLINE | ID: mdl-26588473

ABSTRACT

BACKGROUND: Air pollution is one of the most environmental health concerns in the world and has serious impact on human health, particularly in the mucous membranes of the respiratory tract and eyes. However, ocular hazardous effects to air pollutants are scarcely found in the literature. DESIGN: Panel study to evaluate the effect of different levels of ambient air pollution on lacrimal film cytokine levels of outdoor workers from a large metropolitan area. METHODS: Thirty healthy male workers, among them nineteen professionals who work on streets (taxi drivers and traffic controllers, high pollutants exposure, Group 1) and eleven workers of a Forest Institute (Group 2, lower pollutants exposure compared to group 1) were evaluated twice, 15 days apart. Exposure to ambient PM2.5 (particulate matter equal or smaller than 2.5 µm) was 24 hour individually collected and the collection of tears was performed to measure interleukins (IL) 2, 4, 5 and 10 and interferon gamma (IFN-γ) levels. Data from both groups were compared using Student's t test or Mann- Whitney test for cytokines. Individual PM2.5 levels were categorized in tertiles (lower, middle and upper) and compared using one-way ANOVA. Relationship between PM2.5 and cytokine levels was evaluated using generalized estimating equations (GEE). RESULTS: PM2.5 levels in the three categories differed significantly (lower: ≤22 µg/m3; middle: 23-37.5 µg/m3; upper: >37.5 µg/m3; p<0.001). The subjects from the two groups were distributed unevenly in the lower category (Group 1 = 8%; Group 2 = 92%), the middle category (Group 1 = 89%; Group 2 = 11%) and the upper category (Group 1 = 100%). A significant relationship was found between IL-5 and IL-10 and PM2.5 levels of the group 1, with an average decrease of 1.65 pg/mL of IL-5 level and of 0.78 pg/mL of IL-10 level in tear samples for each increment of 50 µg/m3 of PM2.5 (p = 0.01 and p = 0.003, respectively). CONCLUSION: High levels of PM2.5 exposure is associated with decrease of IL-5 and IL-10 levels suggesting a possible modulatory action of ambient air pollution on ocular surface immune response.


Subject(s)
Air Pollutants/adverse effects , Automobile Driving , Environmental Exposure/adverse effects , Lacrimal Apparatus/drug effects , Occupational Exposure/adverse effects , Adult , Aged , Air Pollutants/immunology , Brazil , Cities , Humans , Immunomodulation , Interferon-gamma/biosynthesis , Interferon-gamma/metabolism , Interleukin-10/biosynthesis , Interleukin-10/metabolism , Interleukin-2/biosynthesis , Interleukin-2/metabolism , Interleukin-4/biosynthesis , Interleukin-4/metabolism , Interleukin-5/biosynthesis , Interleukin-5/metabolism , Lacrimal Apparatus/immunology , Lacrimal Apparatus/metabolism , Male , Middle Aged , Particulate Matter/adverse effects , Particulate Matter/immunology , Tears/chemistry , Tears/immunology , Vehicle Emissions/analysis
8.
Rev. colomb. cir ; 30(3): 198-202, jul.-set. 2015. tab
Article in Spanish | LILACS, COLNAL | ID: lil-765597

ABSTRACT

Introducción. La apendicectomía por laparoscopia es uno de los procedimientos más frecuentemente practicados por el cirujano general. Aunque es un procedimiento estandarizado, suelen ser necesarias pequeñas variaciones en la técnica y el uso de herramientas como la sutura mecánica. Objetivos. Los objetivos del estudio fueron: a) comparar la tasa de complicaciones entre los pacientes en quienes se utilizó Hem-o-lok® y endosutura Vs. sutura mecánica, durante este procedimiento, b) comparar la estancia hospitalaria y la tasa de nuevas hospitalizaciones entre los dos grupos, y c) determinar las indicaciones del cirujano sobre el uso de la sutura mecánica para la ligadura de la base apendicular durante una apendicectomía por laparoscopia. Materiales y métodos. Se hizo una revisión retrospectiva de una base de datos. Se compararon las tasas de complicaciones intraoperatorias y posoperatorias de 222 pacientes con ligadura de la base apendicular, con Hem-o-lok® y endosutura (grupo A) Vs. 35 con sutura mecánica (grupo B), así como la estancia hospitalaria de pacientes en quienes se practicó la apendicectomía por laparoscopia por el Departamento de Cirugía General de la Fundación Clínica Shaio. Además, se determinó cuál fue la indicación por parte del cirujano sobre el uso de la sutura mecánica en estos pacientes. Resultados. De 257 pacientes sometidos a apendicectomía por laparoscopia, en 222 la ligadura de la base apendicular se hizo con Hem-o-lok® y endosutura (grupo A) y, en 35 pacientes, con sutura mecánica (grupo B). Cinco pacientes presentaron complicaciones infecciosas asociadas al procedimiento, todos correspondientes al grupo A. La estancia hospitalaria fue similar en ambos grupos (grupo A: 2,3 ± 2 días; grupo B: 2,6 ± 2 días). No se presentaron nuevas hospitalizaciones. Las indicaciones para el uso de sutura mecánica según el cirujano que practicó el procedimiento, fueron el edema o la perforación en la base apendicular y el ciego. Conclusiones. Las indicaciones para la sutura mecánica en la ligadura de la base apendicular en nuestros pacientes, fueron el edema y la perforación de la base apendicular y el ciego. Los resultados de este estudio muestran que la tasa de complicaciones en quienes se utilizó Hem-o-lok® y endosutura es mayor que en aquellos con sutura mecánica, pero sin una diferencia estadísticamente significativa. La estancia hospitalaria y la tasa de reingreso entre ambos grupos, fueron similares. El uso de la sutura mecánica se considera una variación en el procedimiento, seguro, sencillo y equivalente al de Hem-o-lok® y endosutura.Palabras clave: apendicitis; apendicectomía laparoscópica; técnicas de sutura.


Background. Laparoscopic appendectomy is one of the most frequently performed procedures by the general surgeon. Although it is standardized, minor variations in technique and tools like the use of endo GIA stapler may become necessary. Aims. The aim of our study was: a) To compare the complication rates among patients in whom hemolock and endoloops or endo GIA stapler were used during this procedure, b) To compare the length of hospital stay and readmission rate between the two groups c) To determine the reasons why the surgeons decided to use the stapler for the appendiceal stump closure during a laparoscopic appendectomy. Materials and Methods. Retrospective review of a database. We compared the rate of intra and postoperative complications in 222 patients with appendiceal stump closure with hemolock and endoloops (Group A) vs 35 patients with endo GIA stapler (Group B), as well as length of hospital stay of patients who underwent laparoscopic appendectomy by the General Surgery Department at the Fundación Shaio Clinic (Bogotá, Colombia). In addition, we determined the reasons the surgeons had to decide on the use of the stapler during a laparoscopic appendectomy. Results. Among 257 patients undergoing laparoscopic appendectomy, the appendiceal stump closure was perfomed with hemolock or endoloops in 222 (Group A), and with endo GIA stapler (Group B) in 35. Five patients had infectious complications associated with the procedure. The hospital-stays were similar in both groups (group A: 2.3±2 days, group B: 2.6±2 days). There were no readmissions. The reasons why the surgeons decided to use the stapler, were edema and perforation. Conclusions. The results of our study show that the postoperative complication rate was higher in patients with hemolock and endoloop, but without statistical significance. The hospital stay and readmission rate were similar and the reasons why the surgeons decided to use the stapler were edema and perforation. We consider the use of endo GIA stapler in the appendiceal stump closure a safe and simple procedure and of equal results as those of Hem-o-lok® and endosuture.


Subject(s)
Humans , Appendicitis , Appendectomy , Laparoscopy , Suture Techniques
9.
Rev Iberoam Micol ; 32(4): 261-4, 2015.
Article in English | MEDLINE | ID: mdl-25959551

ABSTRACT

BACKGROUND: Nowadays several invertebrate pollinators of crops and wild plants are in decline as result of multiple and, sometimes, unknown factors; among them, the modern agricultural practices, pests and diseases are postulated as the most important factors. Bees of the genus Xylocopa are considered effective pollinators of passion fruit crops in tropical regions, as well as important pollinators in wild plants, but these bees are attacked by several pathogens that affect different stages in their life cycle. The fungal species of the genus Ascosphaera are commonly associated with social and solitary bee larvae causing chalkbrood disease. AIMS: The aim of the present study was to demonstrate the presence of Ascosphaera apis affecting larvae of Xylocopa augusti in South America. METHODS: For this purpose, A. apis was isolated from affected larvae in YGPSA medium. Final identification was run out by three techniques: (1) Microscopic examination of the hyphae and sizes of the fruiting bodies; (2) Mating test, and specific sexual compatibility test, and (3) PCR detection, using specific primers. RESULTS: This study demonstrates for the first time the presence of A. apis affecting larvae of X. augusti in South America. CONCLUSIONS: The evidence of A. apis affecting the larvae of X. augusti, and the fact that the sharing of pathogens between different bee species has been underestimated, suggests the need for further epidemiological studies in order to determine not only the prevalence of this pathogen among wild pollinators, but also its relationship to the sudden collapse of honey bee colonies in this region.


Subject(s)
Ascomycota/isolation & purification , Bees/microbiology , Animals , Argentina , Ascomycota/ultrastructure , Bees/growth & development , Hyphae/ultrastructure , Larva/microbiology , Species Specificity , Spores, Fungal
11.
Asian Pac J Cancer Prev ; 15(23): 10061-6, 2014.
Article in English | MEDLINE | ID: mdl-25556426

ABSTRACT

BACKGROUND: The aetiological relationship between human papillomavirus (HPV) infection and cervical cancer (CC) is widely accepted. Our goal was to determine the prevalence of HPV types in Mexican women attending at the Mexican Institute for Social Security from different areas of Mexico. MATERIALS AND METHODS: DNAs from 2,956 cervical samples were subjected to HPV genotyping: 1,020 samples with normal cytology, 931 with low-grade squamous intraepithelial lesions (LGSIL), 481 with high grade HGSIL and 524 CC. RESULTS: Overall HPV prevalence was 67.1%. A total of 40 HPV types were found; HPV16 was detected in 39.4% of the HPV-positive samples followed by HPV18 at 7.5%, HPV31 at 7.1%, HPV59 at 4.9%, and HPV58 at 3.2%. HPV16 presented the highest prevalence both in women with altered or normal cytology and HPV 18 presented a minor prevalence as reported worldwide. The prevalence ratio (PR) was calculated for the HPV types. The analysis of PR showed that HPV16 presents the highest association with CC, HPV 31, -33, -45, -52 and -58 also demonstrating a high association. CONCLUSIONS: The most prevalent HPV types in cervical cancer samples were -16, -18, -31, but it is important to note that we obtained a minor prevalence of HPV18 as reported worldwide, and that HPV58 and -52 also were genotypes with an important prevalence in CC samples. Determination of HPV genotypes is very important in order to evaluate the impact of vaccine introduction and future cervical cancer prevention strategies.


Subject(s)
Carcinoma, Squamous Cell/virology , Papillomaviridae/genetics , Papillomavirus Infections/virology , Squamous Intraepithelial Lesions of the Cervix/virology , Uterine Cervical Neoplasms/virology , Adolescent , Adult , Aged , Carcinoma, Squamous Cell/epidemiology , Female , Genotype , Human papillomavirus 16/genetics , Human papillomavirus 18/genetics , Human papillomavirus 31/genetics , Humans , Mexico/epidemiology , Middle Aged , Papillomavirus Infections/epidemiology , Prevalence , Squamous Intraepithelial Lesions of the Cervix/epidemiology , Uterine Cervical Neoplasms/epidemiology , Young Adult
12.
Mol Pharmacol ; 81(4): 567-77, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22241372

ABSTRACT

High-conductance calcium-activated potassium (Maxi-K) channels are present in smooth muscle where they regulate tone. Activation of Maxi-K channels causes smooth muscle hyperpolarization and shortening of action-potential duration, which would limit calcium entry through voltage-dependent calcium channels leading to relaxation. Although Maxi-K channels appear to indirectly mediate the relaxant effects of a number of agents, activators that bind directly to the channel with appropriate potency and pharmacological properties useful for proof-of-concept studies are not available. Most agents identified to date display significant polypharmacy that severely compromises interpretation of experimental data. In the present study, a high-throughput, functional, cell-based assay for identifying Maxi-K channel agonists was established and used to screen a large sample collection (>1.6 million compounds). On the basis of potency and selectivity, a family of tetrahydroquinolines was further characterized. Medicinal chemistry efforts afforded identification of compound X, from which its two enantiomers, Y and Z, were resolved. In in vitro assays, Z is more potent than Y as a channel activator. The same profile is observed in tissues where the ability of either agent to relax precontracted smooth muscles, via a potassium channel-dependent mechanism, is demonstrated. These data, taken together, suggest that direct activation of Maxi-K channels represents a mechanism to be explored for the potential treatment of a number of diseases associated with smooth muscle hyperexcitability.


Subject(s)
Large-Conductance Calcium-Activated Potassium Channels/physiology , Muscle, Smooth/physiology , Animals , CHO Cells , Chromatography, Liquid , Cricetinae , Cricetulus , Large-Conductance Calcium-Activated Potassium Channels/agonists , Magnetic Resonance Spectroscopy , Mass Spectrometry , Muscle Relaxation
13.
J Gen Physiol ; 127(2): 191-204, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16446507

ABSTRACT

High conductance, calcium- and voltage-activated potassium (BK, MaxiK) channels are widely expressed in mammals. In some tissues, the biophysical properties of BK channels are highly affected by coexpression of regulatory (beta) subunits. The most remarkable effects of beta1 and beta2 subunits are an increase of the calcium sensitivity and the slow down of channel kinetics. However, the detailed characteristics of channels formed by alpha and beta1 or beta2 are dissimilar, the most remarkable difference being a reduction of the voltage sensitivity in the presence of beta1 but not beta2. Here we reveal the molecular regions in these beta subunits that determine their differential functional coupling with the pore-forming alpha-subunit. We made chimeric constructs between beta1 and beta2 subunits, and BK channels formed by alpha and chimeric beta subunits were expressed in Xenopus laevis oocytes. The electrophysiological characteristics of the resulting channels were determined using the patch clamp technique. Chimeric exchange of the different regions of the beta1 and beta2 subunits demonstrates that the NH3 and COOH termini are the most relevant regions in defining the behavior of either subunit. This strongly suggests that the intracellular domains are crucial for the fine tuning of the effects of these beta subunits. Moreover, the intracellular domains of beta1 are responsible for the reduction of the BK channel voltage dependence. This agrees with previous studies that suggested the intracellular regions of the alpha-subunit to be the target of the modulation by the beta1-subunit.


Subject(s)
Large-Conductance Calcium-Activated Potassium Channel alpha Subunits/chemistry , Large-Conductance Calcium-Activated Potassium Channel alpha Subunits/metabolism , Large-Conductance Calcium-Activated Potassium Channel beta Subunits/chemistry , Large-Conductance Calcium-Activated Potassium Channel beta Subunits/metabolism , Animals , Female , Gene Expression , Humans , Large-Conductance Calcium-Activated Potassium Channel alpha Subunits/genetics , Large-Conductance Calcium-Activated Potassium Channel beta Subunits/genetics , Membrane Potentials , Myometrium/cytology , Myometrium/physiology , Oocytes/physiology , Patch-Clamp Techniques , Potassium Channels, Voltage-Gated/chemistry , Protein Structure, Tertiary , Structure-Activity Relationship , Xenopus
14.
Br J Pharmacol ; 138(1): 57-62, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12522073

ABSTRACT

1 A constant intraluminal pressure system was used to evaluate the effects of Kv1 channel blockers on the peristaltic activity of guinea-pig ileum. 2 The nortriterpene correolide, a non-selective inhibitor of all Kv1 sub-types, causes progressive and sustained reduction of the pressure threshold for eliciting peristaltic contractions. 3 Margatoxin (MgTX), alpha-dendrotoxin (alpha-DTX) and dendrotoxin-K (DTX-K), highly selective peptidyl inhibitors of certain Kv1 sub-types, cause immediate reduction of the pressure threshold. This effect subsides with time, irrespective of the peptides' concentration in the bath. In preparations pretreated with saturating concentrations of MgTX, correolide further stimulates the peristaltic activity. 4 Iberiotoxin (IbTX), a selective inhibitor of the high-conductance Ca(2+)-activated K(+) (BK) channels, and charybdotoxin (ChTX), which inhibits Kv1.2 and Kv1.3 as well as BK channels, fail to stimulate the peristaltic activity. 5 Blockade of muscarinic receptors by atropine reduces, and occasionally suppresses the peristaltic activity of guinea-pig ileum. In atropine-treated preparations, correolide and MgTX retain their abilities to reduce the pressure threshold and are able to restore the peristaltic reflex in the preparations where this reflex was suppressed by atropine. 6 The stimulatory effect of correolide and MgTX in atropine-treated preparations is abolished by subsequent addition of selective antagonists of both NK1 and NK2 receptors. 7 In conclusion, blockade of Kv1, particularly Kv1.1 channels, increases the peristaltic activity of guinea-pig ileum by enhancing the release of neurotransmitters at the enteric nervous system. In contrast, stimulation of the myogenic motility by blockade of BK channels does not affect the threshold for the peristaltic reflex.


Subject(s)
Enteric Nervous System/drug effects , Ileum/drug effects , Ileum/innervation , Peristalsis/drug effects , Peristalsis/physiology , Potassium Channel Blockers/pharmacology , Potassium Channels/physiology , Acetylcholine/metabolism , Animals , Dose-Response Relationship, Drug , Enteric Nervous System/metabolism , Enteric Nervous System/physiology , Female , Guinea Pigs , Ileum/metabolism , In Vitro Techniques , Male , Shaker Superfamily of Potassium Channels , Tachykinins/metabolism
15.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; Braz. J. Psychiatry (São Paulo, 1999, Impr.);22(2): 72-5, jun. 2000.
Article in Portuguese | LILACS | ID: lil-270348

ABSTRACT

Introdução: O trabalho analisou redações sobre alcoolismo de candidatos a dezessete cursos no vestibular de 1996 na Universidade Federal do Espírito Santo. O objetivo foi identificar concepções sobre causas, consequências e propostas de intervenção em relação ao fenômeno do alcoolismo. Métodos: Foram analisadas 2.578 redações (47,7 por cento). Na organização dos dados foi usado um roteiro contendo categorias de causas, conseguências e propostas de intervenção, construído a partir do exame de um conjunto de redações. Resultados: Os sujeitos mostraram concepções que enfatizam o papel da bebida alcoólica no lidar com situações de caráter negativo e o papel da pressão social como fatores causadores do alcoolismo. Entre as consequências do alcoolismo apareceram com destaque as familiares, as psíquicas e a dependência. Como proposta para lidar com o alcoolismo aparece com bastante destaque o conjunto de providências incluídas sob o rótulo mudanças nas políticas públicas em relação ao comércio e à propaganda de bebidas alcoólicas e também em relação à difusão de informações adequadas sobre as consequências prejudiciais do consumo de tais substâncias. Conclusões: As concepções são similares em todos os grupos de cursos pretendidos pelos candidatos e oscilam entre uma compreensão moral-legal e uma compreensão médico-social do fenômeno


Subject(s)
Substance-Related Disorders
16.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; Braz. J. Psychiatry (São Paulo, 1999, Impr.);2(22): 72-75, jun. 2000.
Article | Index Psychology - journals | ID: psi-15901

ABSTRACT

Introducao: O trabalho analisou redacoes sobre alcoolismo de cadndidatos de dezessete cursos no vestibular de 1996 na Universidade Federal do Espirito Santo. O objetivo foi identificar concepcoes sobre causas, consequencias e propostas de intervencao em relacao ao fenomeno do alcoolismo. Metodos: Foram analisadas 2.578 redacoes (47,7). Na organizacao dos dados foi usado um roteiro contendo categorias de causas, consequencias e propostas de intervencao, construindo a partir do exame de um conjunto de redacoes. Resultados: Os sujeitos mostraram concepcoes que enfatizam o papel da bebida alcoolica no lidar com situacoes de carater negativo e o papel da pressao social como fatores causadores do alcoolismo. Entre as consequencias do alcoolismo apareceram como destaque as familiares, as psiquicas e a dependencia. Como proposta para lidar com o alcoolismo aparece com bastante destaque o conjunto de providencias incluidas sob o rotulo mudancas nas politicas publicas em relacao ao comercio e a propaganda de bebidas alcoolicas e tambem em relacao a difusao de informacoes adequadas sobre as consequencias prejudiciais do consumo de tais substancias. Conclusoes: As concepcoes sao similares em todos os grupos de cursos pretendidos pelos candidatos e oscilam entre uma compreensao moral-legal e uma compreencao medico-social do fenomeno.


Subject(s)
Alcoholism , Students , Adolescent , Alcoholism , Students , Young Adult
17.
Arq. neuropsiquiatr ; Arq. neuropsiquiatr;55(1): 136-8, mar. 1997. ilus
Article in English | LILACS | ID: lil-194716

ABSTRACT

The case of 22-year old, white woman with bilateral orbital myositis following an acute upper respiratory tract infection is reported. The most important clinical findings were ocular pain, proptosis, restricted eye motility and swelling of the eyelids. The enlarged eye muscles were seen on orbital computerized tomography scan. The clinical findings of inflammatory orbital myositis and clinical response to corticotherapy are emphasized.


Subject(s)
Humans , Female , Adult , Orbital Pseudotumor , Acute Disease , Glucocorticoids/therapeutic use , Orbital Pseudotumor/drug therapy , Orbital Pseudotumor/virology , Prednisone/therapeutic use , Respiratory Tract Infections/complications , Tomography, X-Ray Computed
18.
Rev. méd. domin ; 54(2): 25-8, jul.-sept. 1993. ilus
Article in Spanish | LILACS | ID: lil-132096

ABSTRACT

Mediante un estudio prospectivo, transversal se realizó una investigación en 38 pacientes, a los que se les practicó histerectomia por mioma uterino en la Maternidad Nuestra Señora de la Altagracia. El período de estudio fue del 1 de enero de 1991 al 4 de abril del mismo año, así como los meses de agosto, septiembre hasta el 18 de octubre de 1991. El objetivo consistió en determinar el perfil de esas pacientes. Los principales resultados de esta investigación fueron: que el 26.3 por ciento tuvo una edad comprendida entre 41-45 años; el mayor número de embarazos fue de 2-4 (42.1 por ciento ); en cuanto al número de partos, el mayor número correspondio de 2-4 (47.4 por ciento ). Al 68.4 por ciento de las pacientes no se les realizó cesárea. El síntoma más frecuente fue el sangrado con un 33 por ciento y el diagnóstico histopatológico más frecuente fue mioma con 84.2


Subject(s)
Humans , Female , Pregnancy , Adult , Hysterectomy , Myoma , Prospective Studies
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