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1.
Front Physiol ; 13: 769924, 2022.
Article in English | MEDLINE | ID: mdl-35450164

ABSTRACT

Gestational Diabetes Mellitus (GDM) is a highly prevalent maternal pathology characterized by maternal glucose intolerance during pregnancy that is, associated with severe complications for both mother and offspring. Several risk factors have been related to GDM; one of the most important among them is genetic predisposition. Numerous single nucleotide polymorphisms (SNPs) in genes that act at different levels on various tissues, could cause changes in the expression levels and activity of proteins, which result in glucose and insulin metabolism dysfunction. In this review, we describe various SNPs; which according to literature, increase the risk of developing GDM. These SNPs include: (1) those associated with transcription factors that regulate insulin production and excretion, such as rs7903146 (TCF7L2) and rs5015480 (HHEX); (2) others that cause a decrease in protective hormones against insulin resistance such as rs2241766 (ADIPOQ) and rs6257 (SHBG); (3) SNPs that cause modifications in membrane proteins, generating dysfunction in insulin signaling or cell transport in the case of rs5443 (GNB3) and rs2237892 (KCNQ1); (4) those associated with enzymes such as rs225014 (DIO2) and rs9939609 (FTO) which cause an impaired metabolism, resulting in an insulin resistance state; and (5) other polymorphisms, those are associated with growth factors such as rs2146323 (VEGFA) and rs755622 (MIF) which could cause changes in the expression levels of these proteins, producing endothelial dysfunction and an increase of pro-inflammatory cytokines, characteristic on GDM. While the pathophysiological mechanism is unclear, this review describes various potential effects of these polymorphisms on the predisposition to develop GDM.

2.
Eur Cell Mater ; 41: 216-232, 2021 03 01.
Article in English | MEDLINE | ID: mdl-33644848

ABSTRACT

Conventional root canal treatment replaces the infected pulp with defined materials. Alternative cell-based tissue engineering strategies aim to regenerate a fully functional pulp within the root canal. Despite recent advances in this area, however, the regeneration of an innervated pulp remains a major challenge in the field. Both graphene (2DG) and pulsed electromagnetic fields (PEMFs) independently have been shown to promote diverse cellular developmental programs. The present study showed that 2DG promoted the neurogenic induction of human dental pulp stem cells (hDPSCs) by upregulating and accelerating the expression of mature neuronal markers. Notably, 2DG induced the highest expression of transient receptor potential canonical cation channel type 1 (TRPC1) during early neurogenesis. As brief PEMF exposure promotes in vitro differentiation by activating a TRPC1-mitochondrial axis, an opportunity to combine 2DG with developmentally targeted PEMF exposure for synergistic effects was realizable. Neurogenic gene expression, neurotransmitter release, and reactive oxygen species (ROS) production were greatly enhanced by a brief (10 min) and low amplitude (2 mT) PEMF exposure timed to coincide with the highest TRPC1 expression from hDPSCs on 2DG. In contrast, hDPSCs on glass were less responsive to PEMF exposure. The capacity of PEMFs to promote neurogenesis was precluded by the administration of penicillin/streptomycin, mirroring previous studies demonstrating that aminoglycoside antibiotics block TRPC1-mediated calcium entry and verifying the contribution of TRPC1 in this form of magnetoreception. Hence, graphene created a more conducive environment for subsequent PEMF-stimulated neurogenic induction of hDPSCs through their mutual capacity to activate TRPC1with subsequent ROS production.


Subject(s)
Dental Pulp/cytology , Graphite/chemistry , Neurogenesis/physiology , Stem Cells/cytology , TRPC Cation Channels/metabolism , Cell Differentiation/physiology , Cell Line , Cell Proliferation/physiology , Dental Pulp/metabolism , Electromagnetic Fields , Humans , Regeneration/physiology , Stem Cells/metabolism , Tissue Engineering/methods
3.
Radiología (Madr., Ed. impr.) ; 62(1): 3-12, ene.-feb. 2020. ilus, tab
Article in Spanish | IBECS | ID: ibc-194141

ABSTRACT

Los pacientes con heridas penetrantes y sospecha de cuerpos extraños retenidos representan un motivo frecuente de consulta en los servicios de urgencias. Es necesario un estudio radiográfico para descartar la presencia de cuerpos extraños. Sin embargo, las radiografías solo resultan de utilidad en los objetos radiopacos (metal, vidrio, piedra y algunos plásticos). Cuando la sospecha diagnóstica es alta y el estudio radiográfico es negativo, es necesario realizar otras pruebas de imagen. La ecografía ha demostrado su utilidad en la identificación y localización de cuerpos extraños tanto radiopacos como radiotransparentes. La ecografía permite una excelente evaluación de las estructuras adyacentes (músculos, tendones, ligamentos y estructuras neurovasculares) y ha demostrado ser de utilidad en la valoración de sus lesiones asociadas. Los diferentes materiales de los cuerpos extraños presentan patrones ecográficos característicos que resultan de utilidad para su aproximación diagnóstica. Por último, es importante estar familiarizado con los potenciales errores diagnósticos para evitar falsos positivos


Patients with penetrating wounds with suspected foreign bodies retained in the wound are often seen in emergency departments. Imaging studies are necessary to rule out the presence of retained foreign bodies. Plain-film X-rays, however, are only useful when the foreign bodies contain radiopaque material (metal, glass, stone, and some plastics). In cases with strong diagnostic suspicion and negative plain films, other imaging tests are necessary. Ultrasonography has proven useful in the identification and location of both radiopaque and radiotransparent foreign bodies. Ultrasonography enables excellent assessment of adjacent anatomical structures (muscles, tendons, ligaments, and neurovascular structures) and of associated lesions. The different materials found in foreign bodies have characteristic ultrasonographic patterns that are useful for diagnosis. Finally, it is important to be familiar with the diagnostic pitfalls to avoid false positives


Subject(s)
Humans , Male , Female , Child , Middle Aged , Foreign Bodies/diagnostic imaging , Ultrasonography/methods , Diagnostic Errors , Subcutaneous Tissue/diagnostic imaging , Subcutaneous Tissue/injuries , Foreign Bodies/complications , Ultrasonography, Doppler, Color/methods
4.
Ann Hum Biol ; 47(1): 76-80, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31888385

ABSTRACT

Background: The CLOCK (circadian locomotor output cycle kaput) gene is a central regulator of circadian rhythm. The CLOCK gene has been related to energy intake and therefore to nutritional status. However, its specific associations with aspects of food behaviour in children have been scarcely investigated.Aim: To determine the association between the CLOCK gene polymorphism 3111 T > C and eating behaviours in children based on nutritional status.Methods: A cross-sectional study of the association between a CLOCK gene variant and eating behaviour in children (n = 256) was performed. Eating behaviour was evaluated by the Child Eating Behaviour Questionnaire (CEBQ). In addition, the genotype of the CLOCK 3111 T > C (TT, CC, TC) gene polymorphism and BMI were determined.Results: The obese carriers of the C allele of the polymorphism had lower scores in the dimensions "response to satiety" and "slowness to eat" (p < 0.001), both of which constitute an anti-intake dimension and are related to food satiety.Conclusions: The C allele CLOCK gene could be considered a genetic risk factor for satiety-altered eating behaviour dimensions.


Subject(s)
CLOCK Proteins/genetics , Feeding Behavior , Nutritional Status , Polymorphism, Single Nucleotide , Adolescent , Child , Chile , Cross-Sectional Studies , Female , Humans , Male
5.
Radiologia (Engl Ed) ; 62(1): 3-12, 2020.
Article in English, Spanish | MEDLINE | ID: mdl-31351687

ABSTRACT

Patients with penetrating wounds with suspected foreign bodies retained in the wound are often seen in emergency departments. Imaging studies are necessary to rule out the presence of retained foreign bodies. Plain-film X-rays, however, are only useful when the foreign bodies contain radiopaque material (metal, glass, stone, and some plastics). In cases with strong diagnostic suspicion and negative plain films, other imaging tests are necessary. Ultrasonography has proven useful in the identification and location of both radiopaque and radiotransparent foreign bodies. Ultrasonography enables excellent assessment of adjacent anatomical structures (muscles, tendons, ligaments, and neurovascular structures) and of associated lesions. The different materials found in foreign bodies have characteristic ultrasonographic patterns that are useful for diagnosis. Finally, it is important to be familiar with the diagnostic pitfalls to avoid false positives.


Subject(s)
Foreign Bodies/diagnostic imaging , Subcutaneous Tissue/diagnostic imaging , Ultrasonography , Wounds, Penetrating/complications , Calcinosis/diagnostic imaging , Cicatrix/diagnostic imaging , Diagnostic Errors , Foreign Bodies/complications , Glass , Hematoma/diagnostic imaging , Humans , Metals , Plants , Sesamoid Bones/diagnostic imaging , Tomography, X-Ray Computed
7.
J Physiol Biochem ; 73(1): 29-35, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27730429

ABSTRACT

Studies conducted in monozygotic and dizygotic twins have established a strong genetic component in eating behavior. Rare mutations and common variants of the melanocortin 4 receptor (MC4R) gene have been linked to obesity and eating behavior scores. However, few studies have assessed common variants in MC4R gene with the rewarding value of food in children. The objective of the study was to evaluate the association between the MC4R rs17782313 polymorphism with homeostatic and non-homeostatic eating behavior patterns in Chileans children. This is a cross-sectional study in 258 Chilean children (44 % female, 8-14 years old) showing a wide variation in BMI. Anthropometric measurements (weight, height, Z-score of BMI and waist circumference) were performed by standard procedures. Eating behavior was assessed using the Eating in Absence of Hunger Questionnaire (EAHQ), the Child Eating Behavior Questionnaire (CEBQ), the Three-Factor Eating Questionnaire (TFEQ), and the Food Reinforcement Value Questionnaire (FRVQ). Genotype of the rs17782313 nearby MC4R was determined by a Taqman assay. Association of the rs17782313 C allele with eating behavior was assessed using non-parametric tests. We found that children carrying the CC genotype have higher scores of food responsiveness (p value = 0.02). In obese girls, carriers of the C allele showed lower scores of satiety responsiveness (p value = 0.02) and higher scores of uncontrolled eating (p value = 0.01). Obese boys carrying the C allele showed lower rewarding value of food in relation to non-carriers. The rs17782313 C allele is associated with eating behavior traits that may predispose obese children to increased energy intake and obesity.


Subject(s)
3' Untranslated Regions , Genetic Predisposition to Disease , Hyperphagia/genetics , Overweight/etiology , Pediatric Obesity/etiology , Polymorphism, Genetic , Receptor, Melanocortin, Type 4/genetics , Adolescent , Alleles , Body Mass Index , Case-Control Studies , Child , Chile , Cross-Sectional Studies , Feeding Behavior , Female , Genetic Association Studies , Humans , Hyperphagia/metabolism , Hyperphagia/physiopathology , Male , Receptor, Melanocortin, Type 4/metabolism , Reinforcement, Psychology , Reward , Waist Circumference
8.
Rev. cienc. salud (Bogotá) ; 12(1): 23-34, ene.-abr. 2014. tab
Article in Spanish | LILACS, COLNAL | ID: lil-703854

ABSTRACT

Objetivo: Adaptar culturalmente el cuestionario LINQ (Lung Information Needs Questionnaire) en pacientes con enfermedad pulmonar crónica. Métodos: Estudio descriptivo, después de la traducción del cuestionario por traductor certificado y de la adaptación cultural, se aplicó en ocho pacientes para identificar las dificultades y dudas relacionadas con el entendimiento de las preguntas, la terminología y para evaluar no solo la calidad de la traducción, sino también para verificar aspectos prácticos de su aplicación. Posteriormente, se realizó una segunda traducción al idioma inglés la cual fue enviada a los autores para asegurar el contenido original del cuestionario y conseguir el aval para su uso. Resultados: La muestra en la fase de adaptación cultural fue constituida por 6 hombres y 2 mujeres con una edad promedio de 61 años. La versión en español del LINQ y la adaptación cultural fue comprensible y fácil de usar y no presentó discrepancias con la versión original durante el proceso de retratraducción. Conclusiones: La traducción al español y la adaptación del LINQ fue adecuada pues los pacientes no manifestaron dificultades para entender y responder las preguntas. Esto podrá facilitar la realización de futuros estudios que evalúen el componente educativo en los programas de rehabiltación pulmonar.


Objective: To perform a cultural adaptation of the LINQ (Lung Information Needs Questionnaire) for patients with chronic pulmonary disease. Method: Descriptive study. After the translation of the questionnaire by a certified translator, and after its cultural adaptation, it was applied in eight patients in order to identify the difficulties and doubts related to an understanding of the questions and of its terminology, not only to evaluate the quality of the translation, but to verify practical aspects of its application, as well. Afterward, a second translation was done from Spanish to English, and sent back to the authors to ensure the original content of the questionnaire was maintained, and to obtain endorsement for its use. Results: During the cultural adaptation phase, the sample was constituted by 6 men and 2 women, with an average age of 61 years. The Spanish version of the LINQ, as well as the cultural adaptation, was easy to use and did not show any discrepancies with the original version during the re-translation process. Conclusions: The LINQ's translation to Spanish and the cultural adaptation proved to be adequate, because the patients did not express any difficulties in understanding and answering the questions. This will facilitate future studies that evaluate the educational component in the pulmonary rehabilitation program.


Objetivo: adaptar culturalmente o questionário LINQ (Lung Information Needs Questionnaire) em pacientes com doença pulmonar crônica. Métodos: Estudo descritivo, depois da tradução do questionário por tradutor certificado e da adaptação cultural, aplicou-se a oito pacientes para identificar as dificuldades e dúvidas relacionadas com o entendimento das perguntas, a terminologia e para avaliar não só a qualidade da tradução, más também para verificar aspectos práticos de sua aplicação. Posteriormente, realizou-se uma segunda tradução ao idioma inglês a qual foi enviada aos autores para assegurar o conteúdo original do questionário e conseguir o aval para seu uso. Resultados: a amostra na fase de adaptação cultural foi constituída por 6 homens e 2 mulheres com uma idade média de 61 anos. A versão em espanhol de LINQ e a adaptação cultural foram compreensíveis e fáceis de usar e não apresentaram discrepâncias com a versão original durante o processo de retradução. Conclusões: a tradução ao espanhol e a adaptação do LINQ foi adequada pois os pacientes não manifestaram dificuldades para entender e responder as perguntas. Isto poderá facilitar a realização de futuros estudos que avaliem o componente educativo nos programas de reabilitação pulmonar.


Subject(s)
Humans , Pulmonary Disease, Chronic Obstructive , Rehabilitation , Surveys and Questionnaires , Reproducibility of Results , Adaptation to Disasters
9.
Nutr Hosp ; 26(3): 441-50, 2011.
Article in English | MEDLINE | ID: mdl-21892559

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) is the most important cause of chronic liver disease and is considered the hepatic manifestation of the metabolic syndrome associated with diabetes mellitus type 2. The prevalence of NAFLD in the general population reaches 15-20%. It is also estimated that nonalcoholic steatohepatitis (NASH) affects 3% of the population. NAFLD refers to a wide spectrum of liver damage, which ranges from simple steatosis or intracellular triglyceride accumulation, to inflammation (NASH), fibrosis and cirrhosis. The mechanisms involved in the accumulation of triglycerides in the liver and subsequent hepatocellular damage are multifactorial and are not completely understood. However, metabolic changes such as insulin resistance (IR) are developed, being a common factor in the retention of fatty acids (FA) within the hepatocytes with oxidation and production of free radicals at the mitochondrial level, which are capable of causing lipid peroxidation, cytokine production, and necrosis. In addition, there are alterations in the hepatic bioavailability of long chain n-3 polyunsaturated fatty acids, conditions that alter the expression of a series of transcriptional factors involved in lipolytic and lipogenic processes in the liver. A greater knowledge of the etiopathogenic mechanisms of NAFLD is fundamental for the development of future effective therapeutic strategies. The pathophysiological fundamentals of liver steatosis are analyzed in this study.


Subject(s)
Fatty Liver/metabolism , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/metabolism , Fatty Acids/metabolism , Fatty Liver/complications , Fatty Liver/etiology , Fatty Liver/genetics , Fatty Liver/physiopathology , Humans , Insulin Resistance , Metabolic Syndrome/complications , Metabolic Syndrome/metabolism , Non-alcoholic Fatty Liver Disease , Transcription Factors
10.
Nutr Neurosci ; 13(2): 71-8, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20406574

ABSTRACT

OBJECTIVE: To screen for mutations in the coding region of the melanocortin-4 receptor (MC4R) gene and to assess the association between the rs17782313 variant near MC4R with childhood obesity and eating behavior. SUBJECTS AND METHODS: A cross-sectional sample of 221 obese Chilean children and 268 parents were incorporated in the study to assemble 134 case-parent trios. We performed direct sequencing of the MC4R coding region while the rs17782313 variant was genotyped by a Taqman assay. Eating behavior scores were calculated using the Child Eating Behavior and Three Factor Eating Questionnaires adapted for Chilean families. RESULTS: A low frequency of genetic variation in the coding region of MC4R was found in Chilean obese children (Thr150Ile mutation and polymorphisms Ile251Leu and Val103Ile). The rs17782313 variant is possibly associated with satiety responsiveness (P = 0.01) and enjoyment of food scores (P = 0.03). CONCLUSION: The rs17782313 variant may influence eating behavior in obese children.


Subject(s)
Feeding Behavior , Nerve Tissue Proteins/genetics , Obesity/genetics , Polymorphism, Genetic , Receptor, Melanocortin, Type 4/genetics , Amino Acid Substitution , Anthropometry , Appetite , Child , Child Behavior , Chile , Cross-Sectional Studies , DNA Mutational Analysis , Female , Genetic Association Studies , Heterozygote , Humans , Male , Nerve Tissue Proteins/chemistry , Obesity/blood , Open Reading Frames/genetics , Parents , Polymorphism, Single Nucleotide , Receptor, Melanocortin, Type 4/chemistry , Satiety Response , Statistics as Topic , Surveys and Questionnaires
11.
Nutrition ; 26(7-8): 760-5, 2010.
Article in English | MEDLINE | ID: mdl-20144537

ABSTRACT

OBJECTIVE: To evaluate the association between melanocortin-3 receptor common genetic polymorphisms with childhood obesity and eating behavior in Chilean families. METHODS: Two hundred twenty-nine obese children (6-12 y old, body mass index >95th percentile of Centers for Disease Control and Prevention/National Center for Health Statistics, 2000) and 270 parents were selected. Genotypes for MC3R genetic markers -239A>G, 17C>A (Thr6Lys), 241G>A (Val81Ile), +2138InsCAGACC, and microsatellite D20s32e were determined. Eating behavior scores were computed using the Child Eating Behavior Questionnaire and a shorter version of the Three Factor Eating Questionnaire adapted for evaluating eating inclinations in children. Genotype-obesity associations were assessed by the Transmission Disequilibrium Test. Non-parametric tests were used to compare eating behavior scores across study groups. RESULTS: Allelic frequencies of -239G, 17A, 241A, and +2138InsCAGACC were estimated as 4.5%, 5.9%, 5.6%, and 17.6%, respectively, in obese children. The Transmission Disequilibrium Test in case-parent trios revealed no significant associations between childhood obesity and genetic markers, including the microsatellite D20s32e. In girls, we found significantly higher scores of the emotional eating subscale in carriers of the +2138InsCAGACC compared with non-carriers (P=0.04). In boys, carriers of 17A and 241A showed lower scores for the emotional eating subscale (P=0.01), whereas carriers of +2138InsCAGACC showed significantly lower scores for the enjoyment of food subscale compared with non-carriers (P=0.04). CONCLUSIONS: There is not sufficient evidence to support the contribution for common melanocortin-3 receptor variants in childhood obesity. However, our results are concordant for a role of melanocortin-3 receptor variants in some dimensions of eating behavior such as emotional eating and enjoyment of food.


Subject(s)
Alleles , Emotions , Feeding Behavior/psychology , Genotype , Obesity/genetics , Polymorphism, Genetic , Receptor, Melanocortin, Type 3/genetics , Child , Chile , Female , Genetic Markers , Humans , Male , Microsatellite Repeats , Obesity/psychology , Pleasure , Sex Factors , Surveys and Questionnaires
12.
J Microsc ; 237(1): 63-9, 2010 Jan.
Article in English | MEDLINE | ID: mdl-20055919

ABSTRACT

Myoblast therapy relies on the integration of skeletal muscle stem cells into distinct muscular compartments for the prevention of clinical conditions such as heart failure, or bladder dysfunction. Understanding the fundamentals of myogenesis is hence crucial for the success of these potential medical therapies. In this report, we followed the rearrangement of the surface membrane structure and the actin cytoskeletal organization in C2C12 myoblasts at different stages of myogenesis using atomic force microscopy (AFM) and confocal laser scanning microscopy (CLSM). AFM imaging of living myoblasts undergoing fusion unveiled that within minutes of making cell-cell contact, membrane tubules appear that unite the myoblasts and increase in girth as fusion proceeds. CLSM identified these membrane tubules as built on scaffolds of actin filaments that nucleate at points of contact between fusing myoblasts. In contrast, similarly behaving membrane tubules are absent during cytokinesis. The results from our study in combination with recent findings in literature further expand the understanding of the biochemical and membrane structural rearrangements involved in the two fundamental cellular processes of division and fusion.


Subject(s)
Microscopy, Atomic Force/methods , Muscle Development , Actins/physiology , Actins/ultrastructure , Animals , Cell Fusion , Cell Line , Cytokinesis , Heart Failure/therapy , Humans , Mice , Microscopy, Confocal/methods , Microtubule Proteins/physiology , Microtubule Proteins/ultrastructure , Myoblasts/cytology , Myoblasts/physiology , Sensitivity and Specificity , Stem Cell Transplantation , Time Factors , Urinary Bladder Diseases/therapy
13.
Br J Dermatol ; 150(1): 119-26, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14746625

ABSTRACT

BACKGROUND: Griseofulvin has been the mainstay of treatment for tinea imbricata (TI) for decades; however, there have been few reports of efficacy of newer antifungals in the treatment of this condition. Many patients with TI have several obstacles to treatment due to their remote geographical locations and the primitive nature of their societies. OBJECTIVES: The aim of this study was to compare the efficacy of itraconazole, terbinafine and fluconazole with that of griseofulvin after 4 weeks of therapy. METHODS: Patients aged 12-76 years with the clinical diagnosis of TI were randomly assigned to one of four treatment groups: griseofulvin 500 mg twice daily for 4 weeks, terbinafine 250 mg daily for 4 weeks, itraconazole 200 mg twice daily for 1 week or fluconazole 200 mg once weekly for 4 weeks. Disease activity was monitored weekly. Laboratory measurements included monitoring complete blood count and liver function enzymes. Fifty-nine patients were included in the efficacy analysis: 13 in the fluconazole group, 15 in the griseofulvin group, 12 in the terbinafine group and 19 in the itraconazole group. RESULTS: Significant remission was achieved in the terbinafine and griseofulvin groups, lasting up to 8 weeks after cessation of therapy. The fluconazole group experienced no significant remission, and remission was of short duration in the itraconazole group. No adverse events were reported, and non-compliance with medications or follow-up was the only reason for removal from the study. CONCLUSIONS: Griseofulvin and terbinafine are effective in the treatment of TI. The decision of whether to treat at all and which medication to choose depends greatly on the extent of involvement, the social situation, and the availability of resources such as laboratory testing and follow-up.


Subject(s)
Antifungal Agents/therapeutic use , Tinea/drug therapy , Adolescent , Adult , Aged , Child , Female , Fluconazole/therapeutic use , Griseofulvin/therapeutic use , Humans , Itraconazole/therapeutic use , Male , Middle Aged , Naphthalenes/therapeutic use , Prospective Studies , Skin/microbiology , Terbinafine , Tinea/pathology , Treatment Outcome
14.
Cardiovasc Res ; 53(1): 97-104, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11744017

ABSTRACT

OBJECTIVE: Oxygen (O(2)) tension is a major regulator of blood flow in the coronary circulation. Hypoxia can produce vasodilation through activation of ATP regulated K(+) (K(ATP)) channels in the myocyte membrane, which leads to hyperpolarization and closure of voltage-gated Ca(2+) channels. However, there are other O(2)-sensitive mechanisms intrinsic to the vascular smooth muscle since hypoxia can relax vessels precontracted with high extracellular K(+), a condition that prevents hyperpolarization following opening of K(+) channels. The objective of the present study was to determine whether inhibition of Ca(2+) influx through voltage-dependent channels participates in the response of coronary myocytes to hypoxia. METHODS: Experiments were performed on porcine anterior descendent coronary arterial rings and on enzymatically dispersed human and porcine myocytes of the same artery. Cytosolic [Ca(2+)] was measured by microfluorimetry and whole-cell currents were recorded with the patch clamp technique. RESULTS: Hypoxia (O(2) tension approximately 20 mmHg) dilated endothelium-denuded porcine coronary arterial rings precontracted with high K(+) in the presence of glibenclamide (5 microM), a blocker of K(ATP) channels. In dispersed human and porcine myocytes, low O(2) tension decreased basal cytosolic [Ca(2+)] and transmembrane Ca(2+) influx independently of K(+) channel activation. In patch clamped cells, hypoxia reversibly inhibited L-type Ca(2+) channels. RT-PCR indicated that rHT is the predominant mRNA variant of the alpha(1C) Ca(2+) channel subunit in human coronary myocytes. CONCLUSION: Our study demonstrates, for the first time in a human preparation, that voltage-gated Ca(2+)channels in coronary myocytes are under control of O(2) tension.


Subject(s)
Calcium Channels, L-Type/metabolism , Coronary Vessels , Hypoxia/metabolism , Muscle, Smooth, Vascular/metabolism , Animals , Calcium/metabolism , Calcium Channels, L-Type/genetics , Cytosol/metabolism , Fluorometry , Glyburide/pharmacology , Humans , In Vitro Techniques , Patch-Clamp Techniques , Potassium Channel Blockers/pharmacology , RNA, Messenger/analysis , Reverse Transcriptase Polymerase Chain Reaction , Swine , Vasodilation
15.
Biophys J ; 79(1): 202-14, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10866948

ABSTRACT

The outer nuclear membrane, endoplasmic reticulum, and mitochondrial membrane ion channels are poorly understood, although they are important in the control of compartmental calcium levels, cell division, and apoptosis. Few direct recordings of these ion channels have been made because of the difficulty of accessing these intracellular membranes. Using patch-clamp techniques on isolated nuclei, we measured distinct ion channel classes on the outer nuclear envelope of T-cell (human Jurkat) and BFL5 cell (murine promyelocyte) lines. We first imaged the nuclear envelopes of both Jurkat and FL5 cells with atomic force microscopy to determine the density of pore proteins. The nuclear pore complex was intact at roughly similar densities in both cell types. In patch-clamp recordings of Jurkat nuclear membranes, Cl channels (105 +/- 5 pS) predominated and inactivated with negative pipette potentials. Nucleotides transiently inhibited the anion channel. In contrast, FL5 nuclear channels were cation selective (52 +/- 2 pS), were inactivated with positive membrane potentials, and were insensitive to GTPgammaS applied to the bath. We hypothesize that T- and B-cell nuclear membrane channels are distinct, and that this is perhaps related to their unique roles in the immune system.


Subject(s)
B-Lymphocytes/metabolism , Ion Channels/biosynthesis , Nuclear Envelope/metabolism , T-Lymphocytes/metabolism , Animals , Anions/metabolism , B-Lymphocytes/cytology , Cations/metabolism , Cell Line , Cell Nucleus/metabolism , Cell Nucleus/ultrastructure , Chloride Channels/biosynthesis , Humans , Ion Channel Gating/physiology , Jurkat Cells , Mice , Microscopy, Atomic Force , Nuclear Envelope/ultrastructure , Nuclear Proteins/biosynthesis , Patch-Clamp Techniques , Second Messenger Systems/physiology , T-Lymphocytes/cytology
16.
Behav Pharmacol ; 11(1): 57-61, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10821209

ABSTRACT

Polyamines are polycations present at high concentrations in the mammalian brain. We investigated the effect of an intrahippocampal infusion of spermidine, a polyamine agonist, immediately post-training on the inhibitory avoidance learning paradigm in rats. Bilateral intrahippocampal microinjection of spermidine (0.02-20 nmol) caused an increase in test step-down latencies at low concentrations. Administration of arcaine (0.002-0.2 nmol), an antagonist of the N-methyl-D-aspartate (NMDA) receptor polyamine binding site, did not modify the test step-down latencies. In contrast, co-administration of arcaine and spermidine completely reversed the facilitatory effect of spermidine on the test step-down latencies. These results provide evidence that polyamines may be involved in learning and memory modulation.


Subject(s)
Avoidance Learning/drug effects , Hippocampus/physiology , Spermidine/pharmacology , Animals , Biguanides/pharmacology , Injections , Male , Motor Activity/drug effects , Rats , Rats, Wistar , Spermidine/administration & dosage
17.
Eur J Cell Biol ; 79(2): 81-91, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10727016

ABSTRACT

The sea urchin egg has thousands of secretory vesicles known as cortical granules. Upon fertilization, these vesicles undergo a Ca2+-dependent exocytosis. G-protein-linked mechanisms may take place during the egg activation. In somatic cells from mammals, GTP-binding proteins of the Rho family regulate a number of cellular processes, including organization of the actin cytoskeleton. We report here that a crude membrane fraction from homogenates of Strongylocentrotus purpuratus sea urchin eggs, incubated with C3 (which ADP-ribosylates specifically Rho proteins) and [32P]NAD, displayed an [32P]ADP-ribosylated protein of 25 kDa that had the following characteristics: i) identical electrophoretic mobility in SDS-PAGE gels as the [32P]ADP-ribosylated Rho from sea urchin sperm; ii) identical mobility in isoelectro focusing gels as human RhoA; iii) positive cross-reactivity by immunoblotting with an antibody against mammalian RhoA. Thus, unfertilized S. purpuratus eggs contain a mammalian RhoA-like protein. Immunocytochemical analyses indicated that RhoA was localized preferentially to the cortical granules; this was confirmed by experiments of [32P]ADP-ribosylation with C3 in isolated cortical granules. Rho was secreted and retained in the fertilization membrane after insemination or activation with A23187. It was observed that the Rho protein present in the sea urchin sperm acrosome was also secreted during the exocytotic acrosome reaction. Thus, Rho could participate in those processes related to the cortical granules, i.e., in the Ca2+-regulated exocytosis or actin reorganization that accompany the egg activation.


Subject(s)
Ovum/physiology , Sea Urchins/physiology , rhoA GTP-Binding Protein/physiology , Animals , Cytoplasmic Granules/physiology , Cytoplasmic Granules/ultrastructure , Fertilization , Humans , Microscopy, Immunoelectron , Ovum/ultrastructure
18.
Int J Dermatol ; 39(1): 45-50, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10651967

ABSTRACT

BACKGROUND: Acne affects a large number of young adults, including women, who often present with facial as well as truncal involvement. Systemic antimicrobial agents currently used for the reduction of inflammatory papules and cysts require frequent administration and are sometimes associated with uncomfortable side-effects contributing to a decrease in compliance. METHODS: Ninety-nine episodes of inflammatory acne in 79 patients treated with oral antimicrobial agents were studied retrospectively over a period of 46 weeks. Patients were treated with tetracycline, erythromycin, minocycline, and doxycycline, the most commonly prescribed oral antimicrobials used to treat acne. Individuals that were unable to tolerate this therapy or had failed conventional therapy were treated with the azalide antibiotic azithromycin, given in a single oral 250-mg dose three times a week. The other agents were administered daily in divided doses as is current practice. Patients were also on topical care. RESULTS: The efficacy and reported side-effects were examined for all agents. Significant improvement was noted in 4 weeks. All agents were effective in reducing inflammatory lesions and improving acne. Azithromycin produced a slightly higher percentage of patients with a greater than 80% reduction in their inflammatory acne lesions (85.7%) vs. an average of 77.1% for all other agents. All differences observed were not statistically significant. CONCLUSIONS: The results show that azithromycin is a safe and effective alternative in the treatment of inflammatory acne with few side-effects and good compliance, and suggest the need for further investigation with a clinical trial that will compare the long-term efficacy and tolerability.


Subject(s)
Acne Vulgaris/drug therapy , Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , Acne Vulgaris/pathology , Administration, Oral , Adolescent , Adult , Anti-Bacterial Agents/administration & dosage , Azithromycin/administration & dosage , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome
19.
J Foot Ankle Surg ; 37(4): 319-24, 1998.
Article in English | MEDLINE | ID: mdl-9710785

ABSTRACT

Venous ulceration, a relatively common manifestation of venous hypertension, is often difficult to treat. This article reports the authors' experience with a new wound-healing technology using a bilayered, culture-derived human skin equivalent (HSE, Apligraf) for treatment of venous ulcers. In the patients studied, HSE appeared to promote wound healing in three ways: 1) apparent graft "take"; 2) temporary wound closure (persistence of HSE with subsequent wound re-epithelialization from wound margins); and 3) stimulation of host healing without temporary persistence by acting as a biologic dressing. The demonstrated efficacy of HSE suggests that it will prove useful for promoting the healing of venous ulcers.


Subject(s)
Collagen , Leg Ulcer/therapy , Skin, Artificial , Wound Healing , Aged , Aged, 80 and over , Bandages , Cells, Cultured , Combined Modality Therapy , Female , Humans , Leg Ulcer/physiopathology , Male , Pressure , Skin Transplantation/methods
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