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1.
Rev. chil. infectol ; 40(5)oct. 2023.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1521870

ABSTRACT

Mpox es una zoonosis vírica que causa síntomas similares a la viruela, aunque menos graves. La infección fue descrita inicialmente en África central y occidental. Luego del brote multinacional ocurrido el año 2022, ya no es considerada una emergencia de salud pública de importancia internacional. El mecanismo de transmisión es por contacto físico estrecho o directo con lesiones cutáneas de individuos infectados. Presentamos el caso clínico de una enfermera que se infectó por mpox tras un accidente cortopunzante durante la toma de muestra de una lesión por desteche con bisturí en un paciente con VIH. La transmisión percutánea tuvo un período de incubación corto, seguido de una lesión cutánea y síntomas sistémicos. Aunque infrecuente, se destaca el riesgo de transmisión ocupacional de mpox en la atención clínica. Es importante que el personal sanitario adhiera estrictamente a las medidas de prevención, como el uso de equipo de protección personal y la práctica segura en la toma de muestra.


Monkeypox is a viral zoonosis that causes symptoms similar to smallpox, but less severe. The infection was initially described primarily in central and western Africa. After multi-country outbreak in 2022; it is currently no longer a public health emergency of international concern. The main mode of transmission is through close or direct contact with the skin lesions of an infected individual. We report a case of a nurse was infected with mpox after a needlestick injury during a skin sample collection from an HIV-positive patient. Percutaneous transmission resulted in a short incubation period, followed by a skin lesion and systemic symptoms. This case highlights the risk of occupational transmission of mpox in healthcare settings. It is important for healthcare workers to take rigorous prevention measures, such as the use of appropriate personal protective equipment and safe sample collection practices.

2.
Rev. chil. ortop. traumatol ; 63(3): 178-183, dic.2022. tab, graf
Article in Spanish | LILACS | ID: biblio-1437118

ABSTRACT

OBJETIVOS Determinar la prevalencia de déficit de vitamina D, así como evaluar la seguridad y efectividad de un nuevo método de carga con colecalciferol en pacientes adultos con fractura de tibia. MATERIALES Y MÉTODOS Se reclutaron a 56 pacientes consecutivos con edades entre 18 y 65 años con fractura de tibia ingresados en nuestro hospital durante 1 año. Se determinó el nivel de 25-hidroxivitamina D ([25(OH)-D]) al ingreso y tras suplementación con 100.000 UI semanales de colecalciferol, durante 3 o 5 semanas, en casos de insuficiencia ([25(OH)-D] entre 20 ng/mL y 29,9 ng/mL) o deficiencia ([25(OH)-D] < 20 ng/mL), respectivamente. Se determinó la prevalencia de hipovitaminosis D, el porcentaje de normalización de [25(OH)-D], y los efectos adversos. RESULTADOS Se evaluaron 56 pacientes; 98,2% presentó hipovitaminosis D, y 28 (73,7%) y 10 (26,3%) presentaron déficit e insuficiencia, respectivamente. Tras la suplementación, 92,1% alcanzaron niveles [25(OH)-D] normales. Ningún paciente presentó efectos adversos. DISCUSIÓN La prevalencia de deficiencia de vitamina D en nuestra población fue mayor a la reportada en la literatura. Comprobamos que un esquema de suplementación en altas dosis de vitamina D es seguro, y más efectivo que los previamente recomendados. Este esquema de suplementación puede ser implementado en futuros estudios randomizados. CONCLUSIÓN La prevalencia de hipovitaminosis D en pacientes adultos chilenos con fractura de tibia fue alta (98,2%). El esquema de suplementación con vitamina D propuesto fue efectivo y seguro.


OBJETIVOS Determinar la prevalencia de déficit de vitamina D, así como evaluar la seguridad y efectividad de un nuevo método de carga con colecalciferol en pacientes adultos con fractura de tibia. MATERIALES Y MÉTODOS Se reclutaron a 56 pacientes consecutivos con edades entre 18 y 65 años con fractura de tibia ingresados en nuestro hospital durante 1 año. Se determinó el nivel de 25-hidroxivitamina D ([25(OH)-D]) al ingreso y tras suplementación con 100.000 UI semanales de colecalciferol, durante 3 o 5 semanas, en casos de insuficiencia ([25(OH)-D] entre 20 ng/mL y 29,9 ng/mL) o deficiencia ([25(OH)-D] < 20 ng/mL), respectivamente. Se determinó la prevalencia de hipovitaminosis D, el porcentaje de normalización de [25(OH)-D], y los efectos adversos. RESULTADOS Se evaluaron 56 pacientes; 98,2% presentó hipovitaminosis D, y 28 (73,7%) y 10 (26,3%) presentaron déficit e insuficiencia, respectivamente. Tras la suplementación, 92,1% alcanzaron niveles [25(OH)-D] normales. Ningún paciente presentó efectos adversos. DISCUSIÓN La prevalencia de deficiencia de vitamina D en nuestra población fue mayor a la reportada en la literatura. Comprobamos que un esquema de suplementación en altas dosis de vitamina D es seguro, y más efectivo que los previamente recomendados. Este esquema de suplementación puede ser implementado en futuros estudios randomizados. CONCLUSIÓN La prevalencia de hipovitaminosis D en pacientes adultos chilenos con fractura de tibia fue alta (98,2%). El esquema de suplementación con vitamina D propuesto fue efectivo y seguro.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Tibial Fractures/drug therapy , Vitamin D Deficiency/epidemiology , Cholecalciferol/therapeutic use , Calcium-Regulating Hormones and Agents , Chile/epidemiology , Incidence , Prevalence
3.
J Bone Miner Res ; 34(10): 1851-1861, 2019 10.
Article in English | MEDLINE | ID: mdl-31099911

ABSTRACT

Renal transplantation (RTx) is an effective therapy to improve clinical outcomes in pediatric patients with terminal chronic kidney disease. However, chronic immunosuppression with glucocorticoids (GCs) reduces bone growth and BMD. The mechanisms causing GC-induced growth impairment have not been fully clarified. Fibroblast growth factor 23 (FGF23) is a peptide hormone that regulates phosphate homeostasis and bone growth. In pathological conditions, FGF23 excess or abnormal FGF receptors (FGFR) activity leads to bone growth impairment. Experimental data indicate that FGF23 expression is induced by chronic GC exposure. Therefore, we hypothesize that GCs impair bone growth by increasing FGF23 expression, which has direct effects on bone growth plate. In a post hoc analysis of a multicentric randomized clinical trial of prepubertal RTx children treated with early GC withdrawal or chronic GC treatment, we observed that GC withdrawal was associated with improvement in longitudinal growth and BMD, and lower plasma FGF23 levels as compared with a chronic GC group. In prepubertal rats, GC-induced bone growth retardation correlated with increased plasma FGF23 and bone FGF23 expression. Additionally, GC treatment decreased FGFR1 expression whereas it increased FGFR3 expression in mouse tibia explants. The GC-induced bone growth impairment in tibiae explants was prevented by blockade of FGF23 receptors using either a pan-FGFR antagonist (PD173074), a C-terminal FGF23 peptide (FGF23180-205) which blocks the binding of FGF23 to the FGFR-Klotho complex or a specific FGFR3 antagonist (P3). Finally, local administration of PD173074 into the tibia growth plate ameliorated cartilage growth impairment in GC-treated rats. These results show that GC treatment partially reduces longitudinal bone growth via upregulation of FGF23 and FGFR3 expression, thus suggesting that the FGF23/Klotho/FGFR3 axis at the growth plate could be a potential therapeutic target for the management of GC-induced growth impairment in children.


Subject(s)
Bone Development/drug effects , Bone and Bones/metabolism , Fibroblast Growth Factors/metabolism , Glucocorticoids/administration & dosage , Kidney Transplantation , Receptor, Fibroblast Growth Factor, Type 3/metabolism , Signal Transduction/drug effects , Animals , Bone Density/drug effects , Bone and Bones/pathology , Child , Female , Fibroblast Growth Factor-23 , Follow-Up Studies , Glucocorticoids/adverse effects , Humans , Kidney Failure, Chronic/metabolism , Kidney Failure, Chronic/pathology , Kidney Failure, Chronic/surgery , Klotho Proteins , Male , Membrane Proteins , Mice , Rats , Rats, Sprague-Dawley
4.
Cancers (Basel) ; 10(10)2018 Sep 27.
Article in English | MEDLINE | ID: mdl-30262796

ABSTRACT

Hereditary breast and ovarian cancer syndrome (HBOC) represents 5⁻10% of all patients with breast cancer and is associated with high-risk pathogenic alleles in BRCA1/2 genes, but only for 25% of cases. We aimed to find new pathogenic alleles in a panel of 143 cancer-predisposing genes in 300 Mexican cancer patients with suspicion of HBOC and 27 high-risk patients with a severe family history of cancer, using massive parallel sequencing. We found pathogenic variants in 23 genes, including BRCA1/2. In the group of cancer patients 15% (46/300) had a pathogenic variant; 11% (33/300) harbored variants with unknown clinical significance (VUS) and 74% (221/300) were negative. The high-risk group had 22% (6/27) of patients with pathogenic variants, 4% (1/27) had VUS and 74% (20/27) were negative. The most recurrent mutations were the Mexican founder deletion of exons 9-12 and the variant p.G228fs in BRCA1, each found in 5 of 17 patients with alterations in this gene. Rare VUS with potential impact at the protein level were found in 21 genes. Our results show for the first time in the Mexican population a higher contribution of pathogenic alleles in other susceptibility cancer genes (54%) than in BRCA1/2 (46%), highlighting the high locus heterogeneity of HBOC and the necessity of expanding genetic tests for this disease to include broader gene panels.

5.
Kidney Int ; 93(5): 1131-1141, 2018 05.
Article in English | MEDLINE | ID: mdl-29395333

ABSTRACT

It is accepted that osteoblasts/osteocytes are the major source for circulating fibroblast growth factor 23 (FGF23). However, erythropoietic cells of bone marrow also express FGF23. The modulation of FGF23 expression in bone marrow and potential contribution to circulating FGF23 has not been well studied. Moreover, recent studies show that plasma FGF23 may increase early during acute kidney injury (AKI). Erythropoietin, a kidney-derived hormone that targets erythropoietic cells, increases in AKI. Here we tested whether an acute increase of plasma erythropoietin induces FGF23 expression in erythropoietic cells of bone marrow thereby contributing to the increase of circulating FGF23 in AKI. We found that erythroid progenitor cells of bone marrow express FGF23. Erythropoietin increased FGF23 expression in vivo and in bone marrow cell cultures via the homodimeric erythropoietin receptor. In experimental AKI secondary to hemorrhagic shock or sepsis in rodents, there was a rapid increase of plasma erythropoietin, and an induction of bone marrow FGF23 expression together with a rapid increase of circulating FGF23. Blockade of the erythropoietin receptor fully prevented the induction of bone marrow FGF23 and partially suppressed the increase of circulating FGF23. Finally, there was an early increase of both circulating FGF23 and erythropoietin in a cohort of patients with severe sepsis who developed AKI within 48 hours of admission. Thus, increases in plasma erythropoietin and erythropoietin receptor activation are mechanisms implicated in the increase of plasma FGF23 in AKI.


Subject(s)
Acute Kidney Injury/blood , Bone Marrow Cells/metabolism , Erythroid Precursor Cells/metabolism , Erythropoietin/blood , Fibroblast Growth Factors/blood , Acute Kidney Injury/etiology , Animals , Bone Marrow Cells/drug effects , Disease Models, Animal , Erythroid Precursor Cells/drug effects , Erythropoietin/pharmacology , Fibroblast Growth Factor-23 , Humans , Male , Mice, Inbred C57BL , Prospective Studies , Rats, Sprague-Dawley , Receptors, Erythropoietin/agonists , Receptors, Erythropoietin/metabolism , Recombinant Proteins/pharmacology , Sepsis/blood , Sepsis/complications , Shock, Hemorrhagic/blood , Shock, Hemorrhagic/complications , Time Factors , Up-Regulation
6.
Channels (Austin) ; 11(5): 388-398, 2017 Sep 03.
Article in English | MEDLINE | ID: mdl-28636485

ABSTRACT

Renal sodium reabsorption depends on the activity of the Na+,K+-ATPase α/ß heterodimer. Four α (α1-4) and 3 ß (ß1-3) subunit isoforms have been described. It is accepted that renal tubule cells express α1/ß1 dimers. Aldosterone stimulates Na+,K+-ATPase activity and may modulate α1/ß1 expression. However, some studies suggest the presence of ß3 in the kidney. We hypothesized that the ß3 isoform of the Na+,K+-ATPase is expressed in tubular cells of the distal nephron, and modulated by mineralocorticoids. We found that ß3 is highly expressed in collecting duct of rodents, and that mineralocorticoids decreased the expression of ß3. Thus, we describe a novel molecular mechanism of sodium pump modulation that may contribute to the effects of mineralocorticoids on sodium reabsorption.


Subject(s)
Kidney Tubules/metabolism , Mineralocorticoids/pharmacology , Sodium-Potassium-Exchanging ATPase/metabolism , Aldosterone/pharmacology , Animals , Cell Line , Cell Membrane/metabolism , Epithelial Sodium Channel Agonists/pharmacology , Epithelial Sodium Channels/metabolism , Male , Rats, Sprague-Dawley
7.
Oncol Rep ; 35(4): 2297-305, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26797462

ABSTRACT

Abnormal expression and promoter methylation of microRNAs (miRNAs) are common events during cervical carcinogenesis. Worldwide, infection by types 18 and 16 of human papillomaviruses (HPVs) is considered the major risk factor for cervical cancer development. It has been reported that expression of the miRNAs can be deregulated by specific HPV genotypes. In this study we analyzed the promoter methylation of 22 miRNAs and the expression of three miRNAs in 10 non-squamous intraepithelial lesions (Non-SIL) without HPV16 infection, and 7 Non-SIL, 16 low-grade SIL (LSIL) and 16 cervical cancer samples, all with HPV16 infection. The methylation status was determined using Human Cancer miRNA EpiTect Methyl II Signature PCR Array® and the expression of miR-124, miR-218 and miR-193b was determined by qRT-PCR using individual TaqMan assays. Comparisons of groups defined were performed using the Fisher exact test for categorical variables and Mann-Whitney test for continuous variables. A p-value of <0.05 was considered statistically significant. The methylation levels of miR-124-2, miR-218-1, miR-218-2 and miR-34b/c promoters were significantly higher in cervical cancer than in LSIL samples. The methylation levels of miR-193b promoter were significantly lower in cervical cancer than in LSIL samples. The expression of miR-124 and miR-218 was significantly lower in cervical cancer than in LSIL samples. The expression of miR-193b was significantly higher in cervical cancer than in LSIL and Non-SIL samples. Our results suggest that the abnormal promoter methylation and expression of miR-124, miR-218 and miR-193b are common events during cervical carcinogenesis.


Subject(s)
DNA Methylation , Gene Expression Profiling/methods , MicroRNAs/genetics , Oligonucleotide Array Sequence Analysis/methods , Papillomavirus Infections/genetics , Uterine Cervical Dysplasia/genetics , Uterine Cervical Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Female , Gene Expression Regulation, Neoplastic , Human papillomavirus 16/pathogenicity , Humans , Middle Aged , Promoter Regions, Genetic , Young Adult
8.
Virol J ; 12: 29, 2015 Feb 22.
Article in English | MEDLINE | ID: mdl-25889023

ABSTRACT

BACKGROUND: HPV 16 is the cause of cervical carcinoma, but only a small fraction of women with HPV infection progress to this pathology. Besides persistent infection and HPV integration, several studies have suggested that HPV intratype variants may contribute to the development of cancer. The purpose of this study was to investigate the nucleotide variability and phylogenetically classify HPV 16 E6 variants circulating over a period of 16 years in women from Southern Mexico, and to analyze its association with precursor lesions and cervical carcinoma. METHODS: This study was conducted in 330 cervical DNA samples with HPV 16 from women who were residents of the State of Guerrero, located in Southern Mexico. According of cytological and/or histological diagnosis, samples were divided into the following four groups: no intraepithelial lesion (n = 97), low-grade squamous intraepithelial lesion (n = 123), high-grade squamous intraepithelial lesion (n = 19) and cervical carcinoma (n = 91). HPV 16 E6 gene was amplified, sequenced and aligned with reference sequence (HPV 16R) and a phylogenetic tree was constructed to identify and classify HPV 16 variants. Chi squared was used and data analysis and statistics were done with SPSS Statistics and STATA softwares. RESULTS: Twenty seven HPV 16 E6 variants were detected in women from Southern Mexico, 82.12% belonged to the EUR, 17.58% to AA1 and 0.3% to Afr2a sublineages. The most common was E-G350 (40%), followed by E-prototype (13.03%), E-C188/G350 (11.82%), AA-a (10.61%), AA-c (6.07%) and E-A176/G350 (5.15%). Eight new E6 variants were found and 2 of them lead to amino acid change: E-C183/G350 (I27T) and E-C306/G350 (K68T). The HPV 16 variant that showed the greatest risk of leading to the development of CC was AA-a (OR = 69.01, CI = 7.57-628.96), followed by E-A176/G350 (OR = 39.82, CI = 4.11-386.04), AA-c (OR = 21.16, CI 2.59-172.56), E-G350 (OR = 13.25, CI = 2.02-87.12) and E-C188/G350 (OR = 10.48, CI = 1.39-78.92). CONCLUSIONS: The variants more frequently found in women with cervical carcinoma are E-G350, AA-a, AA-c, E-C188/G350 and E-A176/G350. All of them are associated with the development of cervical carcinoma, however, AA-a showed the highest association. This study reinforces the proposal that HPV 16 AA-a is an oncogenic risk for cervical carcinoma progression in Mexico.


Subject(s)
Carcinoma/virology , Human papillomavirus 16/isolation & purification , Papillomavirus Infections/virology , Uterine Cervical Neoplasms/virology , Adult , Carcinoma/pathology , Female , Human papillomavirus 16/classification , Human papillomavirus 16/genetics , Human papillomavirus 16/physiology , Humans , Mexico , Molecular Sequence Data , Papillomavirus Infections/pathology , Phylogeny , Uterine Cervical Neoplasms/pathology , Young Adult
9.
Oncol Rep ; 33(4): 1639-49, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25672522

ABSTRACT

MicroRNAs (miRNAs) play an essential role in the development and progression of acute leukemia (AL). miR-24 promotes the survival of hematopoietic cells. However, little is known concerning the function of miR-24 in human AL. The aim of the present study was to investigate the clinical significance of miR-24 expression in AL. miR-24 expression in 147 patients with AL and 100 healthy individuals was measured by quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR). The results showed that compared with the healthy individuals, the expression of miR-24 in AL patients was significantly higher (p<0.001). In addition, miR-24 was expressed at significantly higher levels in acute myeloid leukemia (AML) patients and at significantly lower levels in acute lymphoblastic leukemia (ALL) (p<0.001). More importantly, Kaplan-Meier analysis showed that AL patients with high miR-24 expression tended to have shorter overall survival (p<0.05). In the multivariate analysis stratified for known prognostic variables, miR-24 was identified as an independent prognostic marker. Our data indicated that miR-24 upregulation was associated with poor prognosis in AL. miR-24 was identified for the first time as an independent marker for predicting the clinical outcome of AL patients.


Subject(s)
Leukemia, Myeloid, Acute/genetics , MicroRNAs/biosynthesis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , RNA, Neoplasm/biosynthesis , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor , Case-Control Studies , Child , Child, Preschool , Female , Humans , Immunophenotyping , Kaplan-Meier Estimate , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/mortality , Leukocyte Count , Male , MicroRNAs/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Prognosis , RNA, Neoplasm/genetics , Reverse Transcriptase Polymerase Chain Reaction
10.
Rev. chil. cardiol ; 34(2): 120-129, 2015. graf, tab
Article in Spanish | LILACS | ID: lil-762613

ABSTRACT

Introducción: Angiotensina (Ang)-(1-9) posee propiedades anti-hipertensivas y efecto protector a nivel cardiovascular en ratas hipertensas. Sin embargo, se desconoce si estos efectos están asociados a un mecanismo de desbalance de sodio a nivel renal. Objetivo: Determinar si el efecto anti-hipertensivo de Ang-(1-9) está asociado a un mecanismo diurético-na-triurético. Método: Ratas macho Sprague Dawley (200 ± 10g) fueron aleatorizadas para recibir Ang II (400 ng/kgmin) vía bomba osmótica. Como control se utilizaron ratas con operación sham (n=18). Después de 2 semanas desde la instalación de bomba, las ratas Sham e hipertensas fueron randomizadas para recibir vehículo (n=10), Ang-(1-9) (602 ng/kg/min, n=17) o una co-administración de Ang-(1-9) y A779 (100 ng kg-1min-1, n=7 bloqueador del receptor MAS) por 2 semanas. Resultados: Se determinó la presión arterial sistólica (PAS), masa ventricular relativa (MVR), área y perímetro de los cardiomiocitos (AC y PC) y la fracción volumétrica de colágeno total (FVCT). Para evaluar la diuresis y natriuresis se utilizaron ratas normotensas que fueron randomizadas para recibir vehículo (n=8) o Ang-(1-9) (600 ngKg-1min-1, n=8) por 6 días. Se observó un incremento significativo(p<0.05) de PAS (33%), MVR (17%), AC (64%), PC (20%), FVCT (46%). La administración crónica de Ang-(1-9) disminuyó PAS (20%), MVR (13 %), AC (35%), PC (20%) y FVCT (20%). Estos efectos no fueron mediados por el receptor MAS. Al comparar las ratas normotensas tratadas con vehículo o Ang-(1-9), se observó un aumento significativo de la diuresis y natriuresis en los días 2 y 3 en los animales con infusión de Ang-(1-9). Conclusión: Ang-(1-9) reduce la hipertensión y el remodelamiento cardíaco en ratas hipertensas. En animales normotensos se demostró que el tratamiento con Ang-(1-9)-induce diuresis y natriuresis. Este es el primer reporte que señala que el efecto de Ang-(1-9) está asociado a una regulación del sodio a nivel renal.


Background: Angiotensin-(1-9) has anti-hypertensive properties and protective cardiovascular effect in hypertensive rats. However, it is unknown whether its effects are related to a kidney mechanism to balance sodium. Aim: To determine if the anti-hypertensive effect of Ang-(1-9) is associated to a diuretic-natriuretic mechanism. Method: Sprague Dawley male rats (200±10 grs) were randomized to receive Angiotensin II by osmotic pump (400 ng/kg/min). Sham operated rats were utilized as control (n=18). Two weeks after pump setting, Sham rats with hypertension were randomized to receive placebo (n=10), Ang-(1-9)(602 ng/kg/min, n=17) or Ang-(1-9) plus A779 (Ang-(1-7) Receptor Mas blocker, 100ng/kg-1min-1, n=7) co-administration for two weeks. Arterial systolic pressure (PAS), ventricular relative mass (MVR), cardiomyocytes area and perimeter (AC and PC) and total collagen volume fraction (FVCT) were measured. Normotensive rats were utilized to evaluate diuresis and natriuresis which were randomized to receive placebo (n=8) or Ang-(1-9) (600ng/kg-1/min-1, n=8) for six days. Results: It was observed a significant rise (p<0.05) of PAS (33%), MVR (17%), AC (64%), PC (26%), FVCT (46%) was observed. Chronic administration of Ang-(1-9) reduced PAS (20%), MVR (13%), AC (35%), PC (20%) and FCVT (20%). All those effects were not mediated by Mas receptor. A significant raise was observed of diuresis and natriuresis at the second and third day of treatment in rats receiving Ang-(1-9) in comparison with normotensive rats treated with placebo. Conclusion: Ang-(1-9) reduces hypertension and cardiac remodeling in hypertensive rats. Ang-(1-9) induces natriuresis and diuresis in normotensive rats. This is the first report showing that Ang-(1-9) is associated to sodium balance in the kidney.


Subject(s)
Animals , Rats , Angiotensin II/pharmacology , Diuresis/drug effects , Natriuresis/drug effects , Antihypertensive Agents/pharmacology , Rats, Sprague-Dawley , Heart/drug effects
11.
Hypertension ; 63(4): 797-803, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24420551

ABSTRACT

Adaptive immune response has been implicated in inflammation and fibrosis as a result of exposure to mineralocorticoids and a high-salt diet. We hypothesized that in mineralocorticoid-salt-induced hypertension, activation of the mineralocorticoid receptor alters the T-helper 17 lymphocyte (Th17)/regulatory T-lymphocyte/interleukin-17 (IL-17) pathway, contributing to cardiac and renal damage. We studied the inflammatory response and tissue damage in rats treated with deoxycorticosterone acetate and high-salt diet (DOCA-salt), with or without mineralocorticoid receptor inhibition by spironolactone. To determine whether Th17 differentiation in DOCA-salt rats is caused by hypertension per se, DOCA-salt rats received antihypertensive therapy. In addition, to evaluate the pathogenic role of IL-17 in hypertension and tissue damage, we studied the effect of IL-17 blockade with a specific antibody (anti-IL-17). We found activation of Th17 cells and downregulation of forkhead box P3 mRNA in peripheral tissues, heart, and kidneys of DOCA-salt-treated rats. Spironolactone treatment prevented Th17 cell activation and increased numbers of forkhead box P3-positive cells relative to DOCA-salt rats. Antihypertensive therapy did not ameliorate Th17 activation in rats. Treatment of DOCA-salt rats with anti-IL-17 significantly reduced arterial hypertension as well as expression of profibrotic and proinflammatory mediators and collagen deposits in the heart and kidney. We conclude that mineralocorticoid receptor activation alters the Th17/regulatory T-lymphocyte/IL-17 pathway in mineralocorticoid-dependent hypertension as part of an inflammatory mechanism contributing to fibrosis.


Subject(s)
Desoxycorticosterone Acetate/adverse effects , Heart Diseases/prevention & control , Hypertension/chemically induced , Kidney Diseases/prevention & control , Spironolactone/pharmacology , T-Lymphocytes, Regulatory/drug effects , Th17 Cells/drug effects , Animals , Antibodies/immunology , Antibodies/pharmacology , Desoxycorticosterone Acetate/pharmacology , Disease Models, Animal , Down-Regulation/drug effects , Down-Regulation/physiology , Forkhead Transcription Factors/drug effects , Forkhead Transcription Factors/physiology , Heart Diseases/etiology , Heart Diseases/physiopathology , Hypertension/complications , Hypertension/physiopathology , Interleukin-17/antagonists & inhibitors , Interleukin-17/immunology , Interleukin-17/physiology , Kidney Diseases/etiology , Kidney Diseases/physiopathology , Male , Mineralocorticoid Receptor Antagonists/pharmacology , Rats , Rats, Sprague-Dawley , Receptors, Mineralocorticoid/drug effects , Receptors, Mineralocorticoid/physiology , Signal Transduction/drug effects , Signal Transduction/physiology , T-Lymphocytes, Regulatory/pathology , Th17 Cells/pathology
12.
J Hypertens ; 32(4): 771-83, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24463937

ABSTRACT

BACKGROUND: Little is known about the biological effects of angiotensin-(1-9), but available evidence shows that angiotensin-(1-9) has beneficial effects in preventing/ameliorating cardiovascular remodeling. OBJECTIVE: In this study, we evaluated whether angiotensin-(1-9) decreases hypertension and reverses experimental cardiovascular damage in the rat. METHODS AND RESULTS: Angiotensin-(1-9) (600  ng/kg per min for 2 weeks) reduced already-established hypertension in rats with early high blood pressure induced by angiotensin II infusion or renal artery clipping. Angiotensin-(1-9) also improved cardiac (assessed by echocardiography) and endothelial function in small-diameter mesenteric arteries, cardiac and aortic wall hypertrophy, fibrosis, oxidative stress, collagen and transforming growth factor type ß - 1 protein expression (assessed by western blot). The beneficial effect of angiotensin-(1-9) was blunted by coadministration of the angiotensin type 2(AT2) receptor blocker PD123319 (36  ng/kg per min) but not by coadministration of the Mas receptor blocker A779 (100  ng/kg per min). Angiotensin-(1-9) treatment also decreased circulating levels of Ang II, angiotensin-converting enzyme activity and oxidative stress in aorta and left ventricle. Whereas, Ang-(1-9) increased endothelial nitric oxide synthase mRNA levels in aorta as well as plasma nitrate levels. CONCLUSION: Angiotensin-(1-9) reduces hypertension, ameliorates structural alterations (hypertrophy and fibrosis), oxidative stress in the heart and aorta and improves cardiac and endothelial function in hypertensive rats. These effects were mediated by the AT2 receptor but not by the angiotensin-(1-7)/Mas receptor axis.


Subject(s)
Angiotensin II/chemistry , Angiotensin I/chemistry , Angiotensin-Converting Enzyme Inhibitors/chemistry , Cardiovascular Diseases/drug therapy , Hypertension/drug therapy , Peptide Fragments/chemistry , Angiotensin II Type 1 Receptor Blockers/chemistry , Animals , Aorta/pathology , Blood Pressure/drug effects , Cardiovascular Diseases/prevention & control , Disease Models, Animal , Echocardiography , Endothelium, Vascular/pathology , Heart Ventricles , Hemodynamics , Hypertension/physiopathology , Imidazoles/chemistry , Male , Oxidative Stress , Pyridines/chemistry , Rats , Rats, Sprague-Dawley
13.
San Salvador; s.n; 1999. 154 p. Ilus.
Thesis in Spanish | BISSAL, LILACS | ID: biblio-1254533

ABSTRACT

La presente investigación trata acerca del manejo odontológico que le brinda a los pacientes geriátricos en el área de estomatología y cirugía maxilofacial del hospital Rosales y la clínica de consulta externa del Instituto Salvadoreño de rehabilitación de inválidos. La investigación inicia con la determinación de los elementos del diagnostico, donde se justifica el por qué de la investigación, lo que se pretende alcanzar al final de esta, el nivel de generalización de los resultados y lo que cubrirá el estudio a nivel teórico, también se plantean algunas limitaciones que tuvo el grupo investigador en la realización de la misma, los sujetos que formaron parte del estudio y el problema en estudio. Luego se establece un marco de referencia, en el cual se plantean los orígenes, evolución y desarrollo del problema, así como también se explican los diferentes puntos de vista que tienen otros autores con respecto al manejo del paciente geriátrico. En la metodología de la investigación, se explica el tipo de investigación que se realizó, la población a quien fue dirigida, métodos, técnicas e instrumentos que se utilizaron para la realización de los dos primeros capítulos y para la recopilación de los datos, además, se plasma la forma como se elaboraron los instrumentos y su descripción, como se estableció el proceso de recolección de los datos y la manera como se tabularon. En el capítulo final se encuentran los cuadros estadísticos que se realizaron a partir de los resultados de la investigación, cada cuadro presenta su respectiva descripción, luego se encuentra el análisis que el grupo investigador realizó a partir de los resultados obtenidos en el diagnóstico y de su propia experiencia, para luego finalizar con las conclusiones y recomendaciones de la investigación.


This research is about the dental management that it provides to geriatric patients in the area of ​​stomatology and maxillofacial surgery of the Rosales hospital and the outpatient clinic of the Salvadoran Institute for the rehabilitation of invalids. The investigation begins with the determination of the elements of the diagnosis, where the reason for the investigation is justified, what it is intended to achieve at the end of this, the level of generalization of the results and what the study will cover at a theoretical level, as well. Some limitations that the research group had in carrying it out, the subjects who were part of the study and the problem under study are proposed. Then a frame of reference is established, in which the origins, evolution and development of the problem are raised, as well as the different points of view that other authors have regarding the management of the geriatric patient are explained. In the research methodology, the type of research that was carried out, the population to whom it was directed, methods, techniques and instruments that were used to carry out the first two chapters and to collect the data are explained, in addition, the way in which the instruments were elaborated and their description, how the data collection process was established and the way in which they were tabulated, is reflected. In the final chapter are the statistical tables that were made from the results of the research, each table presents its respective description, then there is the analysis that the research group carried out from the results obtained in the diagnosis and its own experience, and then finalize with the conclusions and recommendations of the investigation.


Subject(s)
Geriatric Dentistry , Health of the Elderly , Dental Care for Aged , El Salvador
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