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Pulmonary fibrosis is a complex disease that can occur in a variety of clinical settings. The Zinc Finger and BTB Domain Containing 16 (Zbtb16) is a transcription factor and has not been studied in pulmonary fibrosis. Lung tissues from rats which were treated with bleomycin and Tanshinone IIA (Tan IIA) were collected for mRNA sequencing. Zbtb16, a differentially expressed gene, was screened. Using adeno-associated virus to knock down Zbtb16 in rats, it was found that the lung index and the content of hydroxyproline in lung tissue were decreased. HE and Masson staining revealed that pathological symptoms of lung histopathology were relieved after Zbtb16 knockdown. Protein expressions of α-SMA, Collagen I and Fibronectin were significantly decreased after Zbtb16 knockdown in vivo and in vitro. Meanwhile, the protein content of TGF-ß1 and the phosphorylation of Smad2/3 were inhibited by Zbtb16 knockdown. Conversely, under the treatment of Tan IIA and TGF-ß1, overexpression of Zbtb16 improved cell viability, increased the expression of fibrosis-related proteins, and promoted the phosphorylation of Smad 2/3. All above demonstrates that Zbtb16 inhibition ameliorates pulmonary fibrosis and suppresses the TGF-ß/Smad pathway. Furthermore, Zbtb16 mediates the inhibitory process of Tan IIA on pulmonary fibrosis. This study provides a novel candidate therapeutic target for pulmonary fibrosis.
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Abietanos , Fibrosis Pulmonar , Animales , Ratas , Bleomicina/toxicidad , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/metabolismo , Ratas Sprague-Dawley , Transducción de Señal , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
Kawasaki disease, or mucocutaneous lymph node syndrome, is an acute systemic vasculitis involving small and medium-sized vessels. It can be complicated by varying degrees of cardiac damage, especially coronary artery disease. The disease mainly occurs in children aged < 5 years, with rarer cases in older children and adults. Intravenous immunoglobulin combined with aspirin is the widely accepted treatment regimen in the acute phase, but the dosage recommended by the American Heart Association guidelines is not suitable for heavier children. This article reports the successful management of an overweight 14-year-old child with Kawasaki disease.
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Background and objective: IBS-D is a common functional bowel disease with complex etiology and without biomarker. The pathological and physiological basis of IBS-D focuses on visceral hypersensitivity. However, its epigenetic mechanism remains elusive. Our study aimed to integrate the relationship between differentially expressed miRNAs, mRNAs and proteins in IBS-D patients in order to reveal epigenetic mechanism of visceral hypersensitivity from transcription and protein levels and provide the molecular basis for discovering biomarkers of IBS-D. Methods: The intestinal biopsies from IBS-D patients and healthy volunteers were obtained for high-throughput sequencing of miRNAs and mRNAs. The differential miRNAs were selected and verified by q-PCR experiment followed by target mRNA prediction. Biological functions were respectively analyzed for target mRNAs, differential mRNAs and the previously identified differential proteins in order to explore the characteristic involved visceral hypersensitivity. At last, interaction analysis of miRNAs, mRNAs and proteins was performed for the epigenetic regulation mechanism from transcription and protein levels. Results: Thirty-three miRNAs were found to be differentially expressed in IBS-D and five of them were further confirmed, including upregulated hsa-miR-641, hsa-miR-1843, hsa-let-7d-3p and downregulated hsa-miR-219a-5p, hsa-miR-19b-1-5p. In addition, 3,812 differential mRNAs were identified. Thirty intersecting molecules were found from the analysis on the target mRNAs of miRNAs and mRNAs. Fourteen intersecting molecules were obtained from the analysis on the target mRNAs and proteins, and thirty-six intersecting molecules were identified from analysis on the proteins and different mRNAs. According to the integrated analysis of miRNA-mRNA-protein, we noticed two new molecules COPS2 regulated by hsa-miR-19b-1-5p and MARCKS regulated by hsa-miR-641. Meanwhile some critical signaling pathways in IBS-D were found such as MAPK, GABAergic synapse, Glutamatergic synapse, and Adherens junction. Conclusion: The expressions of hsa-miR-641, hsa-miR-1843, hsa-let-7d-3p, hsa-miR-219a-5p, and hsa-miR-19b-1-5p in the intestinal tissues of IBS-D patients were significantly different. Moreover, they could regulate a variety of molecules and signaling pathways, which were involved in the multifaceted and multilevel mechanism of visceral hypersensitivity of IBS-D.
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Liver fibrosis is a global health problem caused by a number of diseases related to liver damage. 6-Shogaol is a biologically active substance derived from the rhizome of Zingiber officinale Roscoe with anti-tumor, anti-inflammatory, and antioxidant properties. To explore the effects of 6-Shogaol on liver fibrosis, we used a mouse model of the condition in which mice were injected intraperitoneally with carbon tetrachloride (CCl4) at a dose of 2 mL/kg three times per week for a period of 4 weeks. 6-Shogaol was administered orally at two different doses (5 mg/kg, 20 mg/kg) 30 min before CCl4 injection. CCl4 induced severe liver injury and fibrosis, as indicated by significant inflammatory cell infiltration, disordered liver structure, increased activities of aspartate aminotransferase and alanine aminotransferase (liver damage markers) in serum, elevated collagen deposition, and overexpressed alpha-smooth muscle actin (α-SMA, marker of hepatic stellate cells activation) in liver tissues, whereas 6-Shogaol administration rescued those alterations dose-dependently. We found that 6-Shogaol suppressed CCl4-induced inflammatory response by inhibiting macrophage recruitment, release of pro-inflammatory factors, and activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in liver tissues. Additionally, we demonstrated that 6-Shogaol blocked CCl4-induced activation of the nuclear factor-kappa B (NF-κB) pathway, which is a vital transcriptional regulator of the inflammatory response. Altogether, this study demonstrates that 6-Shogaol can prevent CCl4-induced liver fibrosis by suppressing inflammatory response through the NF-κB pathway and suggests that 6-Shogaol can be used for liver fibrosis prevention.
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Antiinflamatorios , Catecoles , Cirrosis Hepática , FN-kappa B , Animales , Antiinflamatorios/farmacología , Tetracloruro de Carbono , Catecoles/farmacología , Hígado/metabolismo , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/metabolismo , Ratones , FN-kappa B/metabolismoRESUMEN
To investigate therapeutic target for ligustrazine during liver fibrosis in an ethanol-induced biliary atresia rat model and transforming growth factor-ß (TGF-ß) induced hepatic stellate cell activation cell model, and the underlying mechanism, a total of 30 rats were randomly assigned into five groups (n = 6 per group): control, sham, ethanol-induced biliary atresia model, model plus pirfenidone, and model plus ligustrazine groups. The liver changes were assessed using H&E and Masson staining and transmission electron microscopy. Expression of miR-145 and mRNA and protein levels of TGF-ß/smads pathway-related proteins were detected. HSC-T6 cells were infected with LV-miR or rLV-miR-145 in the presence or absence of SMAD3 inhibitor SIS3 and treated with 2.5 ng/ml TGF-ß1 and then with ligustrazine. Collected cells were subjected to detect the expression of miR-145 and mRNA and protein expression levels of TGF-ß/smads pathway-related proteins. Ligustrazine rescued liver fibrogenesis and pathology for ethanol-caused bile duct injury, revealed by decreased α-smooth muscle actin and collagen I expression and liver tissue and cell morphology integrity. Further experiments showed that ligustrazine inhibited intrinsic and phosphorylated Smad2/3 protein expression and modification. Similar results were obtained in cells. In addition, ligustrazine altered miR-145 expression in both animal and cell models. Lentivirus mediated miR-145 overexpression and knockdown recombinant virus showed that miR-145 enhanced the TGF-ß/Smad pathway, which led to hepatic stellate cell activation, and ligustrazine blocked this activation. This work validated that ligustrazine-regulated miR-145 mediated TGF-ß/Smad signaling to inhibit the progression of liver fibrosis in a biliary atresia rat model and provided a new therapeutic strategy for liver fibrosis. SIGNIFICANCE STATEMENT: With an ethanol-induced biliary atresia rat model, ligustrazine was found to rescue liver fibrogenesis and pathology for ethanol caused bile duct injury, revealed by decreased α-smooth muscle actin and collagen I expression and liver tissue and cell morphology integrity. Furthermore, we found ligustrazine upregulated miR-145 expression and inhibited TGF-ß/SMAD signaling pathway both in vivo and in vitro. In addition, overexpression and knockdown of miR-145 confirmed that miR-145 is involved in the ligustrazine inhibition of liver fibrosis through the TGF-ß/SMAD signaling pathway.
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Atresia Biliar , MicroARNs , Actinas/genética , Actinas/metabolismo , Animales , Atresia Biliar/metabolismo , Atresia Biliar/patología , Colágeno Tipo I/efectos adversos , Colágeno Tipo I/metabolismo , Modelos Animales de Enfermedad , Etanol/efectos adversos , Células Estrelladas Hepáticas/metabolismo , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Pirazinas , ARN Mensajero/metabolismo , Ratas , Transducción de Señal , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Factores de Crecimiento Transformadores/efectos adversos , Factores de Crecimiento Transformadores/metabolismoRESUMEN
BACKGROUND: Congenital nephrogenic diabetes insipidus (CNDI) is a rare hereditary disorder. It is associated with mutations in the arginine vasopressin receptor 2 (AVPR2) gene and aquaporin 2 (AQP2) gene, and approximately 270 different mutation sites have been reported for AVPR2. Therefore, new mutations and new manifestations are crucial to complement the clinical deficiencies in the diagnosis of this disease. We report a case of a novel AVPR2 gene mutation locus and a new clinical mani-festation. CASE SUMMARY: We describe the case of a 48-d-old boy who presented with recurrent fever and diarrhea 5 d after birth. Laboratory tests showed electrolyte disturbances and low urine specific gravity, and imaging tests showed no abnormalities. Genetic testing revealed a novel X-linked recessive missense mutation, c.283 (exon 2) C>T (p.P95S). This mutation results in the substitution of a proline residue with a serine residue in the AVPR2 protein sequence. The diagnosis of CNDI was confirmed based on the AVPR2 gene mutation. The treatment strategy for this patient was divided into two stages, including physical cooling supplemented with appropriate amounts of water in the early stage and oral hydrochlorothia-zide (1-2 mg/kg) after a clear diagnosis. After follow-up of one and a half years, the patient gradually improved. CONCLUSION: AVPR2 gene mutations in new loci and new clinical symptoms help clinicians understand this disease and shorten the diagnosis cycle.
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IBS-D is a functional bowel disease without clear diagnostic markers and exact pathogenesis. Studies have proved that non-coding RNAs participate in IBS-D. However, tRNA-derived small RNAs (tsRNAs), as a new type of non-coding RNAs that are more suitable as markers, remain to be clarified in IBS-D. Hence, we focused on the identification and potential functions of tsRNAs in IBS-D. Intestinal biopsies were obtained from IBS-D patients and healthy volunteers, and twenty-eight differential tsRNAs were screened by high-throughput sequencing. The changes of tiRNA-His-GTG-001, tRF-Ser-GCT-113, and tRF-Gln-TTG-035 by q-PCR in expanded samples were consistent with the sequencing results. Meanwhile, target gene prediction and bioinformatics showed that the three differential tsRNAs may be involved in some key signal pathways, such as GABAergic synapse, tumor necrosis factor-α (TNF-α), etc. Their regulation on target genes were demonstrated through cell experiments and luciferase reporter assays. In addition, the receiver-operating characteristic (ROC) analysis showed that the three tsRNAs all could be used as candidate markers of IBS-D. The correlation analysis indicated they were related to the degree of abdominal pain, abdominal distension, and stool morphology. So, we believe that the abnormal tiRNA-His-GTG-001, tRF-Ser-GCT-113, and tRF-Gln-TTG-035 are related to the clinical symptoms of IBS-D, and can target regulate the important molecules of the brain-gut axis, even could be expected as potential biomarkers for the diagnosis and treatment of IBS-D.
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Diarrea/genética , Síndrome del Colon Irritable/genética , ARN de Transferencia , Adulto , Biomarcadores , Línea Celular , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Mucosa Intestinal/metabolismo , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Salvianolate, a common drug for stabilizing heart disease and Angina Pectoris, is considered to be off-label for preventing venous thromboembolism (VTE) or anticoagulation at present. However, many clinical studies have showed that salvianolate can effectively inhibit the deep-vein thrombosis (DVT) incidence, and prevent VTE of perioperative patients in the real world in China. OBJECTIVE: This analysis aimed to evaluate the effectiveness and safety of salvianolate in preventing VTE in perioperative patients. METHODS: Databases of PubMed, Cochrane Library, Embase, CNKI, Wanfang and VIP were searched until July 2019. Literature retrieval, data extraction and quality assessment were independently completed by two researchers and checked with each other. Review Manager 5.2 software was applied for meta-analysis. RESULTS: A total of 429 studies were retrieved, including 11 randomized controlled trials (RCTs) with a total of 1149 subjects. Compared with low molecular weight heparin (LMWH) group alone, salvianolate combined LMWH group had lower DVT incidence in preventing perioperative thrombosis (2.75% and 14.23%, OR: 0.21, 95% CI:[0.08,0.53]; Pâ=â.0009). The incidence of adverse reactions of experimental group was similar to that of control group (1.79% and 2.31%, OR: 0.65, 95% CI:[0.18,2.35]. Pâ=â.51). Compared with the control group, D-dimer level (D-D), platelet count (PLT), fibrinogen (FIB), whole blood high shear viscosity (WBHSV), and whole blood low shear viscosity (WBLSV) were all significantly decreased (Pâ<â.01), and prothrombin time (PT) was significantly increased (Pâ<â.05). CONCLUSION: Salvianolate combined LMWH has better effectiveness and the same safety in preventing venous thromboembolism in perioperative patients. However, due to the small number of included literatures, large sample studies are still needed to further verify this conclusion.
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Uso Fuera de lo Indicado , Extractos Vegetales/efectos adversos , Complicaciones Posoperatorias/epidemiología , Procedimientos Quirúrgicos Operativos/efectos adversos , Tromboembolia Venosa/epidemiología , China/epidemiología , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Heparina de Bajo-Peso-Molecular/administración & dosificación , Heparina de Bajo-Peso-Molecular/efectos adversos , Humanos , Periodo Perioperatorio/estadística & datos numéricos , Extractos Vegetales/administración & dosificación , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Tiempo de Protrombina , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & controlRESUMEN
INTRODUCTION: The aim of this study was to evaluate the efficacy and safety of azithromycin (AZI) combined with glucocorticoid (GC) in the treatment of children with refractory Mycoplasma pneumoniae. METHODS: Computer search for PubMed, EMbase, Cochrane Library, China Biomedical Literature Database (CBMdisc), China Knowledge Network (CNKI), Wanfang, VIP (VIP), and a randomized controlled trial (RCT) of AZI combined with GC in the treatment of children with refractory Mycoplasma pneumoniae pneumonia test (RCT), the search time limit is built until March 20, 2019. Two researchers independently performed literature screening, data extraction, and literature risk bias, and meta-analysis was performed using RevMan 5.3 software. RESULTS: A total of 12 RCTs were included, including 1130 patients. Meta-analysis showed that AZI combined with GC therapy significantly improved the total effective rate of the disease compared with the conventional treatment group (odds ratio [OR]â=â6.37; 95% confidence interval [CI] 4.03, 10.07; Pâ<â.00001; Iâ=â0%), effectively shortened the antipyretic time (SMDâ=â-2.29; 95% CI -2.70, -1.88; Pâ<â.0001); promoted lung inflammation absorption (SMDâ=â-1.89; 95% CI -2.38, -1.40; Pâ<â.0001), reduced cough time (SMDâ=â-2.39; 95% CI -2.80, -1.99; Pâ<â.0001); shortened hospital stay (SMDâ=â-2.19; 95% CI -3.21, -1.17; Pâ<â.0001); improved imaging findings (ORâ=â5.38; 95% CI 1.09, 26.51, Pâ=â.04); reduced inflammation index (SMDâ=â-3.15; 95% CI -4.93, -1.36; Pâ=â.004); improved immune function (SMDâ=â1.29; 95% CI -0.02, 2.60; Pâ<â.0001); had no significant adverse reactions (ORâ=â1.18; 95% CI 0.71, 1.98; Pâ=â.53). CONCLUSIONS: According to the current limited research evidence, the addition of GCs to the conventional treatment of refractory Mycoplasma pneumoniae in children can improve the clinical efficacy to a certain extent, and the safety is better. However, due to the quality and quantity of the included literature, the conclusions of this study need to be confirmed by more high-quality studies.
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Antibacterianos/uso terapéutico , Azitromicina/uso terapéutico , Glucocorticoides/uso terapéutico , Mycoplasma pneumoniae , Neumonía por Mycoplasma/tratamiento farmacológico , Antibacterianos/efectos adversos , Azitromicina/efectos adversos , Niño , Tos/tratamiento farmacológico , Tos/microbiología , Quimioterapia Combinada , Fiebre/tratamiento farmacológico , Fiebre/microbiología , Glucocorticoides/efectos adversos , Humanos , Tiempo de Internación , Neumonía por Mycoplasma/complicaciones , Neumonía por Mycoplasma/diagnóstico por imagenRESUMEN
INTRODUCTION: Multiple studies have investigated the effect of ursodeoxycholic acid (UDCA) or glucocorticoid (GC) on the outcome of the hepatoportoenterostomy (Kasai procedure) in patients with biliary atresia (BA). However, the combined effect of these drugs (UDCAâ+âGC) is little understood. METHODS: This meta-analysis specifically evaluated the effect of UDCAâ+âGC after the Kasai procedure in patients with BA. A comprehensive literature search was conducted for all relevant articles in the electronic databases Medline, PubMed, Cochrane, Excerpta Medica Database (EMBASE), China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database on Disc (CBM-disc), and Vendor Information Pages (VIP). RESULTS: Eight studies with BA patients were finally included in our meta-analysis. The 8 identified studies consisted of 3 case-control, 3 cohort, and 2 randomized controlled trials (RCTs) with overall 530 subjects (144, 152, and 234 subjects, respectively). Among them, 312 patients were treated with UDCAâ+âGC, while 218 received placebo or other intervention. The meta-analysis indicated that groups that received UDCAâ+âGC had significantly lower rates of postoperative jaundice relative to the controls (pooled, odds ratio [OR]â=â2.41; 95% confidence interval [CI] 1.44-4.04; Zâ=â3.34; Pâ=â.0008), while rates of cholangitis were similar (pooled, ORâ=â0.87; 95% CI 0.43-1.74; Zâ=â0.40; Pâ=â.69). CONCLUSIONS: Combined UDCA and GC intervention was superior to that of the control in accelerating the clearance of serum bilirubin in patients with BA after the Kasai procedure. However, this conclusion requires further confirmation using RCTs of high methodological quality.
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Atresia Biliar/cirugía , Colagogos y Coleréticos/administración & dosificación , Glucocorticoides/administración & dosificación , Portoenterostomía Hepática/métodos , Ácido Ursodesoxicólico/administración & dosificación , Atresia Biliar/sangre , Bilirrubina/sangre , Quimioterapia Combinada , Femenino , Humanos , Lactante , Recién Nacido , Ictericia/etiología , Ictericia/prevención & control , Masculino , Portoenterostomía Hepática/efectos adversos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Resultado del TratamientoRESUMEN
Objective: To explore the preventive effects of Jiawei Yinchen Sini Decoction on the gene expression of Smad7 and Collagen,â ¢ in mice with hepatic fibrosis. Methods: 48 male ICR mice were randomly divided into normal group, model group, colchicine group, JWYSN high dose group, medium dose group and low dose group, with 8 mice in each group. The hepatic fibrosis model was established by intraperitoneal injection of 30% CCl4( 1. 5 mg/kg, dissolved in olive oil). At the same time, the mice were treated with intragastric adminstration of drugs. After 14 days, the liver index was calculated; the levels of serum hyaluronic acid( HA) and laminin protein( LN) were detected by Enyme-linked immunosorbent assay; the pathological fibrosis change was observed by performing HE staining and was made a grading of hepatic fibrosis. mRNA expression of Smad7 and Collagen I, â ¢ were detected by RT-q PCR analysis. Results: (1) Compared with model group, the liver index and levels of HA and LN in JWYSN medium dose group and low dose group were obviously decreased( P < 0. 05).( 2) The pathological results showed that, compared with model group, the hepatic fibrosis were significantly relief in different dose of JWYSN group( P < 0. 05).( 3) The expressions of Collagen â mRNA in each treatment group were significantly lower than model group( P < 0. 05); In addition to JWYSN high dose group, the expressions of Smad7 mRNA in each treatment group increased significantly( P < 0. 05); In addition to JWYSN low dose group, the expression of Collagenâ ¢mRNA in each treatment group decreased significantly( P < 0. 05). Conclusion: Jiawei Yinchen Sini decoction can up-regulate the expressions of Smad7 mRNA and inhibit expressions of mRNA and Collagenâ ¢mRNA in mice with hepatic fibrosis,thus attenuate the development of hepatic fibrosis.
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Medicamentos Herbarios Chinos , Cirrosis Hepática , Animales , Tetracloruro de Carbono , Colágeno , Modelos Animales de Enfermedad , Laminina , Hígado , Masculino , Ratones , Ratones Endogámicos ICR , Proteína smad7 , Regulación hacia ArribaRESUMEN
OBJECTIVE: To access the prevalence and risk factors for hypertension after heart transplantation (HT), and the impact of post-transplant hypertension on medium-term survival among HT patients. METHODS: Data from 265 consecutive patients underwent HT between June 2004 and May 2012 in Fuwai hospital and survived for at least 6 months were retrospectively analyzed. Hypertension was defined as systolic pressure ≥ 140 mm Hg (1 mm Hg = 0.133 kPa) and/or diastolic pressure ≥ 90 mm Hg or current treatment with antihypertensive drugs. Patients were divided into post-HT hypertension group and non-hypertension group. Logistic regression analysis was used to determine preoperative and postoperative risk factors for hypertension after HT. Kaplan-Meier method and log rank test were used for survival analysis. RESULTS: Hypertension was present in 17.4% (46/265) patients before HT and in 57.4% (152/265) patients post HT. The median follow-up time was 37 months (20 - 57 months). Logistic regression analysis showed that male gender (OR: 2.27, 95%CI: 1.16 - 4.42, P < 0.05), history of pre-HT hypertension (OR: 2.22, 95%CI: 1.05 - 4.71, P < 0.05), and cyclosporine A based immunosuppressive therapy (OR: 2.54, 95%CI: 1.51 - 4.29, P < 0.01) were independent risk factors for the development of post-HT hypertension. At the end of 1, 3, 5 years, the survival rate of heart transplant patients by Kaplan-Meier method estimation were 100%, 97.2%, 86.7% in post-HT hypertension group; 98.1%, 93.8%, 93.8% in non-hypertension group. Log rank test displayed that there was no significant difference between the two survival curves (P > 0.05). CONCLUSIONS: Hypertension is a frequent comorbidity after HT. Male gender, pre-HT hypertension together with cyclosporine A based immunosuppressive therapy are independent predictors for the development of post-HT hypertension. By adjusting the controllable risk factors and active control of blood pressure, the medium-term survival is similar between patients with or without postoperative hypertension in this cohort.
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Trasplante de Corazón , Hipertensión/etiología , Complicaciones Posoperatorias , Adulto , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Pronóstico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Elevated blood glucose (BG) induced by antihypertensive agents increases the risk of cardiovascular events. This study was designed to investigate whether fosinopril+indapamide combination therapy has any effect on glucose tolerance (GT), and if it did, whether conversion to fosinopril alone could reverse the impaired GT. METHODS: Included in the present study were 124 hypertensive patients, of whom 62 patients were treated with fosinopril plus indapamide (F/I group) and the remaining 62 patients were treated with fosinopril alone (F group). Of them, 89 patients completed a mean of 14-month follow-up. In the F/I group, 29 patients were converted to the use of fosinopril for 4-12 months after they completed the follow-up. RESULTS: In the F group, fasting BG decreased significantly from 5.1+/-0.5 to 4.8+/-0.7 mmol/l (p<0.01), and 2-h postprandial BG decreased significantly from 7.2+/-1.6 to 6.4+/-1.4 mmol/l (p<0.01), while in the F/I group, fasting BG increased significantly from 5.1 +/-0.6 to 5.3+/-0.9 mmol/l (p<0.05), and 2-h postprandial BG increased significantly from 7.2+/-1.7 to 7.7+/-1.8 mmol/l (p<0.05). In 29 patients of the F/I group who completed the follow-up and were converted to fosinopril, fasting BG decreased significantly from 5.5+/-1.0 to 5.3+/-1.0 mmol/l (p<0.05), and 2-h postprandial BG decreased significantly from 7.5+/-2.0 to 7.0+/-2.7 mmol/l (p<0.05). CONCLUSION: Fosinopril+indapamide combination therapy impaired GT in Chinese hypertensive patients, and fosinopril alone was able to reverse fosinopril+indapamide-induced GT impairment in part of these patients.
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Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antihipertensivos/efectos adversos , Fosinopril/efectos adversos , Intolerancia a la Glucosa/inducido químicamente , Indapamida/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Antihipertensivos/administración & dosificación , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Índice de Masa Corporal , China , Quimioterapia Combinada , Femenino , Fosinopril/administración & dosificación , Intolerancia a la Glucosa/tratamiento farmacológico , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/metabolismo , Indapamida/administración & dosificación , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Circunferencia de la Cintura , Relación Cintura-CaderaRESUMEN
BACKGROUND: Overweight and obesity are associated with cardiovascular disease (CVD). This study was designed to investigate whether combined use of nitrendipine and atenolol has any effect on body weight (BW) and whether metformin can prevent antihypertensive medication-induced weight gain and has any effect on blood glucose (BG). METHODS: Included in the present study were 94 hypertensive patients with a body mass index (BMI) > or =25 kg/m(2), of whom 45 patients were treated with nitrendipine plus atenolol (N/A group), and the remaining 49 patients were treated with nitrendipine, atenolol, and metformin (N/A/M group). The mean follow-up duration was 14 months. BW and glucose tolerance were measured. RESULTS: In N/A group, BW and fasting BG significantly increased from 73.5 +/- 9.6 kg to 74.2 +/- 9.7 kg (P < 0.05) and from 94.2 +/- 10.5 mg/dl to 97.9 +/- 11.3 mg/dl (P < 0.01), respectively, whereas postprandial BG did not change significantly. In N/A/M group, BW slightly decreased from 72.7 +/- 10.1 kg to 72.3 +/- 10.2 kg (P = 0.30), and fasting BG did not change significantly (93.5 +/- 10.4 mg/dl vs. 92.7 +/- 10.2 mg/dl, P = 0.59), whereas 2-h postprandial BG significantly decreased from 133.7 +/- 30.5 mg/dl to 124.0 +/- 29.6 mg/dl (P < 0.05). Furthermore, a significant difference was observed in difference value of BW before and after treatment between the two groups (0.7 (95% confidence interval, 0.1-1.3) kg in N/A group vs. -0.4 (95% confidence interval, -1.3 to 0.4) kg in N/A/M group, P < 0.05). CONCLUSIONS: Combination therapy of nitrendipine and atenolol may significantly increase BW and fasting BG in overweight or obese patients with hypertension. Metformin may prevent BW gain and improve BG levels in hypertensive patients who received combination therapy of nitrendipine and atenolol.
Asunto(s)
Antagonistas Adrenérgicos beta/efectos adversos , Antihipertensivos/efectos adversos , Atenolol/efectos adversos , Hipertensión/complicaciones , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Aumento de Peso/efectos de los fármacos , Antagonistas Adrenérgicos beta/uso terapéutico , Anciano , Antihipertensivos/uso terapéutico , Atenolol/uso terapéutico , Glucemia/metabolismo , Índice de Masa Corporal , Bloqueadores de los Canales de Calcio/efectos adversos , China , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Prueba de Tolerancia a la Glucosa , Humanos , Hipertensión/tratamiento farmacológico , Resistencia a la Insulina/fisiología , Lípidos/sangre , Masculino , Síndrome Metabólico/complicaciones , Persona de Mediana Edad , Nitrendipino/efectos adversos , Nitrendipino/uso terapéutico , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Sobrepeso/complicaciones , Sobrepeso/tratamiento farmacológico , Estudios ProspectivosRESUMEN
OBJECTIVE: To investigate serum resistin concentration in essential hypertension patients and the relationship between serum resistin level and body fat content, plasma glucose concentration, and blood pressure. METHODS: Fasting serum resistin concentrations were measured with enzyme immunoassay in 71 cases (including 33 men and 38 women), and oral glucose tolerance test and insulin release test were performed in all cases for calculating glucose area under the curve (AUC(G)), the ratio of change in insulin to change in glucose during the first 30 min after glucose ingestion (Delta I(30)/Delta G(30)) and insulin sensitivity index (ISI) according to Cederholm's formula. Systolic pressure (SBP), diastolic pressure (DBP), height, body weight, waist circumference and hip circumference were measured to calculate body mass index (BMI), body fat percentage (BF%) and waist-hip ratio (WHR). RESULTS: Pearson analysis showed that fasting serum resistin concentrations were correlated with AUC(G) (r = 0.380, P < 0.001), BF% (r = 0.353, P < 0.01), ISI (r = -0.242, P < 0.05) and Delta I(30)/Delta G(30) (r = -0.298, P < 0.05), but not correlated with SBP, DBP, BMI and WHR. After adjustment for age and BMI, partial correlation analysis showed that fasting serum resistin concentrations were correlated with AUC(G) (r = 0.268, P < 0.05), Delta I(30)/Delta G(30) (r = -0.247, P < 0.05) and not correlated with ISI. A stepwise multiple linear regression analysis showed that resisitin was a significant independent predictor of AUC(G). CONCLUSION: The strong correlation between fasting serum resistin levels and AUC(G), and BF% suggests a possibility that resistin link obesity to diabetes in humans.