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1.
Eur Rev Med Pharmacol Sci ; 27(13): 6081-6091, 2023 07.
Article in English | MEDLINE | ID: mdl-37458657

ABSTRACT

OBJECTIVE: Sepsis remains a common cause of death. The cereblon (CRBN) protein, which is involved in important cellular processes, plays a role in sepsis. This cross-sectional study aimed to show the CRBN protein expression and its effects on patients in the intensive care unit. PATIENTS AND METHODS: Samples were taken by deep tracheal aspiration from patients. The presence of CRBN was pathologically investigated using immunohistochemical tests and polyclonal antibodies against CRBN. The relationship between gender, sepsis, steroid, survival and the presence of CRBN was examined. RESULTS: Respiratory and neurologic diseases were the most common reasons for admission. Acinetobacter was the most frequent microorganism. In patients with more than normal inflammatory cells, a negative correlation was observed between CRBN expression and leukocyte rate (p=0.031). In patients with CRBN, there was no correlation between steroid and mortality, APACHE/Glasgow score, hospital stay length, and ICU. CONCLUSIONS: Although the prognosis for sepsis is better in CRBN-deficiency animals, the presence of CRBN in humans does not affect it. In our study, CRBN decreased as inflammatory cells increased in the patient's aspiration material. The response to steroids, an immunomodulator, did not change with the presence of the immunomodulator target molecule, CRBN. Therefore, using immunomodulators in the treatment of sepsis should be reconsidered.


Subject(s)
Adaptor Proteins, Signal Transducing , Sepsis , Animals , Humans , Critical Care , Cross-Sectional Studies , Immunologic Factors , Incidence , Intensive Care Units , Ubiquitin-Protein Ligases
2.
Braz J Biol ; 82: e262567, 2022.
Article in English | MEDLINE | ID: mdl-36043660

ABSTRACT

The mycotoxigenic fungus Fusarium verticillioides is the primary maize pathogen and causes the maize stalk and ear rot diseases with significant economic losses. Furthermore, the excessive use of fungicides to control F. verticillioides constitutes threats to the environment and human health. Thus, sustainable alternatives such as biological control are needed to minimize the hazards associated with the current method. Although much is known about the vulnerability of the maize silks as a gateway for several fungal pathogens invading the developing grains, studies on the chemical properties of silk extracts and their resident microbiota are scarce. This study isolated and characterized bacteria and fungi that colonize the maize stigma to assess new potential biocontrol agents. The samples were collected from maize fields in the Brazilian localities of Sete Lagoas-MG, Sidrolândia-MS, Sertaneja-PR, and Goiânia-GO. One hundred sixty-seven microorganisms were isolated, 46% endophytic and 54% epiphytic. First, the antagonist activity was evaluated by the agar disc diffusion method performed in triplicate, and 83% of the isolates showed antagonist activity against F. verticillioides. Then, the 42 most efficient isolates were identified based on the partial sequencing of the bacterial 16S rRNA gene and fungi ITS region. The bacteria belong to the genera Bacillus (57.1%), Burkholderia (23.8%), Achromobacter (7.1%), Pseudomonas (2.4%), and Serratia (2.4%), while the fungi are Penicillium (2.4%), Candida (2.4), and Aspergillus (2.4%). The results showed that microorganisms from maize stigma might represent new promising agents for F. verticillioides control.


Subject(s)
Fusarium , Zea mays , Fusarium/genetics , Humans , Pseudomonas , RNA, Ribosomal, 16S
3.
Acta Gastroenterol Belg ; 85(1): 35-45, 2022.
Article in English | MEDLINE | ID: mdl-35304992

ABSTRACT

Background and study aims: The prognostic value of H. pylori, which infects more than half of the human population living in the world and plays a role in gastric cancer pathogenesis, is controversial. Our aim is to investigate the relationship between H. pylori and prognostic factors in gastric cancer. Patients and methods: The data of 110 patients (38 females and 72 males) that underwent surgeries due to gastric cancer between 2014 and 2017 were retrospectively analyzed. The relationships between survival (disease-free and overall) and factors such as p53, HER2/neu, Ki-67, neutrophil and platelet lymphocyte ratio (NLR / PLR), histopathological and demographic characteristics were examined. In addition, the results of H. pylori positive and negative groups were compared. Results: Sixty-one (55%) patients were H. pylori negative and 49 (45%) were positive. In multivariate analysis, TNM stage, lymph node capsule invasion and NLR were determined as independent prognostic factors in both disease-free and overall survival. Age>62 and PLR>14.3 were determined as independent predictive factors of poor prognosis in overall survival. In univariate analysis, tumor diameter of >4.3 cm, lymphovascular and perineural invasion, and diffuse p53 expression were determined as predictive factors of poor prognosis in disease-free and overall survival. The effectiveness of these markers in prognosis was not different between H. pylori negative and positive groups. Conclusion: While age, tumor diameter, TNM stage, lymph node capsule invasion, perineural and lymphovascular invasion, diffuse p53, PLR, and NLR were determined as prognostic factors in gastric cancer, these factors were not affected by the presence of H. pylori.


Subject(s)
Helicobacter pylori , Stomach Neoplasms , Female , Humans , Lymphocytes/pathology , Male , Middle Aged , Prognosis , Retrospective Studies , Stomach Neoplasms/pathology
4.
Acta Gastroenterol Belg ; 84(4): 607-617, 2021.
Article in English | MEDLINE | ID: mdl-34965043

ABSTRACT

BACKGROUND AND STUDY AIMS: The prognostic value of H. pylori, which infects more than half of the human population living in the world and plays a role in gastric cancer pathogenesis, is controversial. Our aim is to investigate the relationship between H. pylori and prognostic factors in gastric cancer. PATIENTS AND METHODS: The data of 110 patients (38 females and 72 males) that underwent surgeries due to gastric cancer between 2014 and 2017 were retrospectively analyzed. The relationships between survival (disease-free and overall) and factors such as p53, HER2/neu, Ki-67, neutrophil and platelet lymphocyte ratio (NLR / PLR), histopathological and demographic characteristics were examined. In addition, the results of H. pylori positive and negative groups were compared. RESULTS: Sixty-one (55%) patients were H. pylori negative and 49 (45%) were positive. In multivariate analysis, TNM stage, lymph node capsule invasion and NLR were determined as independent prognostic factors in both disease-free and overall survival. Age>62 and PLR>14.3 were determined as independent predictive factors of poor prognosis in overall survival. In univariate analysis, tumor diameter of >4.3 cm, lymphovascular and perineural invasion, and diffuse p53 expression were determined as predictive factors of poor prognosis in disease-free and overall survival. The effectiveness of these markers in prognosis was not different between H. pylori negative and positive groups. CONCLUSION: While age, tumor diameter, TNM stage, lymph node capsule invasion, perineural and lymphovascular invasion, diffuse p53, PLR, and NLR were determined as prognostic factors in gastric cancer, these factors were not affected by the presence of H. pylori.


Subject(s)
Helicobacter pylori , Stomach Neoplasms , Female , Humans , Lymphocytes , Male , Middle Aged , Neutrophils , Prognosis , Retrospective Studies
5.
Dis Markers ; 2018: 9131432, 2018.
Article in English | MEDLINE | ID: mdl-29692871

ABSTRACT

BACKGROUND: We aimed in our study to research the role of new cytokines such as IL-35, IL-22, and IL-17 that may form a target for novel treatment approaches. METHODS: IL-10, IL-17, TGF-ß, IFN-γ, IL-22, and IL-35 serum levels of allergic rhinitis (AR) patients were measured using ELISA method. Allergic sensitization was demonstrated by the skin prick test. Patients only with olive tree sensitivity were evaluated for seasonal AR (SAR). Patients only with mite sensitivity were included in the study for perennial AR (PAR). AR clinic severity was demonstrated by the nasal symptom scores (NSS). RESULTS: In total, 65 AR patients (patient group), having 31 PAR and 34 SAR patients, and 31 healthy individuals (control group) participated in the study. Cytokine levels between the patient group and the control group were compared; IL-17 (p = 0.038), IL-22 (p = 0.001), and TGF-ß (p = 0.031) were detected as high in the patient group, and IFN-γ (p < 0.001) was detected as low in the patient group. When correlation analysis was made between age, gender, prick test result, NSS, AR duration, and cytokine levels in the patient group, a negative correlation was detected only between IFN-γ (p = 0.032/r = -0.266) level and NSS. CONCLUSIONS: Accompanied by the literature information, these results made us think that T cell subgroups and cytokines have an important role in AR immunopathogenesis. It is thought that future studies to be conducted relating to this subject will form new targets in treatment.


Subject(s)
Interferon-gamma/blood , Interleukins/blood , Rhinitis, Allergic/blood , Tumor Necrosis Factor-alpha/blood , Adult , Biomarkers/blood , Female , Humans , Male
6.
Life Sci ; 148: 241-6, 2016 Mar 01.
Article in English | MEDLINE | ID: mdl-26874026

ABSTRACT

AIMS: Melanin-concentrating hormone (MCH) is implicated in the control of food intake, body weight regulation and energy homeostasis. Lactation is an important physiological model to study the hypothalamic integration of peripheral sensory signals, such as suckling stimuli and those related to energy balance. MCH can be detected in the medial preoptic area (MPOA), especially around the 19th day of lactation, when this hormone is described as displaying a peak synthesis followed by a decrease after weaning. The physiological significance of this phenomenon is unclear. Therefore, we aimed to investigate hypothalamic changes associated to sensory stimulation by the litter, in special its influence over MCH synthesis. MAIN METHODS: Female Wistar rats (n=56) were euthanized everyday from lactation days 15-21, with or without suckling stimulus (WS and NS groups, respectively). MCH and Fos immunoreactivity were evaluated in the MPOA and lateral and incerto-hypothalamic areas (LHA and IHy). KEY FINDINGS: Suckling stimulus induced Fos synthesis in all regions studied. An increase on the number of suckling-induced Fos-ir neurons could be detected in the LHA after the 18th day. Conversely, the amount of MCH decreased in the MPOA from days 15-21, independent of suckling stimulation. No colocalization between MCH and Fos could be detected in any region analyzed. SIGNIFICANCE: Suckling stimulus is capable of stimulating hypothalamic regions not linked to maternal behavior, possibly to mediate energy balance aspects of lactation. Although dams are hyperphagic before weaning, this behavioral change does not appear to be mediated by MCH.


Subject(s)
Hypothalamic Hormones/biosynthesis , Hypothalamus/metabolism , Lactation/metabolism , Melanins/biosynthesis , Melanophores/metabolism , Pituitary Hormones/biosynthesis , Proto-Oncogene Proteins c-fos/biosynthesis , Animals , Animals, Suckling , Female , Hypothalamic Hormones/analysis , Melanins/analysis , Pituitary Hormones/analysis , Proto-Oncogene Proteins c-fos/analysis , Rats , Rats, Wistar
7.
Parasite Immunol ; 37(7): 376-9, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25728555

ABSTRACT

In Chagas disease, chronically infected individuals may be asymptomatic or may present cardiac or digestive complications, and it is well known that the human immune response is related to different clinical manifestations. Different patterns of cytokine levels have been previously described in different clinical forms of this disease, but contradictory results are reported. Our aim was to evaluate the serum levels of interleukin-10 and tumour necrosis factor-alpha in patients with asymptomatic and cardiac Chagas disease. The serum interleukin-10 levels in patients with cardiomyopathy were higher than those in asymptomatic patients, mainly in those without heart enlargement. Although no significant difference was observed in serum tumour necrosis factor-alpha levels among the patients, we found that cardiac patients also present high levels of this cytokine, largely those with heart dilatation. Therefore, these cytokines play an important role in chronic Chagas disease cardiomyopathy. Follow-up investigations of these and other cytokines in patients with chronic Chagas disease need to be conducted to improve the understanding of the immunopathology of this disease.


Subject(s)
Chagas Cardiomyopathy/blood , Interleukin-10/blood , Tumor Necrosis Factor-alpha/blood , Adult , Aged , Aged, 80 and over , Chagas Cardiomyopathy/immunology , Chagas Cardiomyopathy/pathology , Chronic Disease , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged
8.
Balkan J Med Genet ; 18(2): 71-76, 2015 Dec 01.
Article in English | MEDLINE | ID: mdl-27785400

ABSTRACT

Limb-girdle muscular dystrophy type 2E (LGMD-2E) is caused by autosomal recessive defects in the beta sarcoglycan (SGCB) gene located on chromosome 4q12. In this case report, the clinical findings, histopathological features and molecular genetic data in a boy with ß sarcoglycanopathy are presented. An 18-month-old boy had a very high serum creatinine phosphokinase (CPK) level that was accidentally determined. The results of molecular analyses for the dystrophin gene was found to be normal. He underwent a muscle biopsy which showed dystrophic features. Immunohistochemistry showed that there was a total loss of sarcolemmal sarcoglycan complex. DNA analysis revealed a large homozygous deletion in the SCGB gene. During 4 years of follow-up, there was no evidence to predict a severe clinical course except the muscle enzyme elevation and myopathic electromyography (EMG) finding. The presented milder phenotype of LGMD-2E with a large deletion in the SGCB gene provided additional support for the clinical heterogeneity and pathogenic complexity of the disease.

9.
Neurol Neurochir Pol ; 47(5): 493-8, 2013.
Article in English | MEDLINE | ID: mdl-24166571

ABSTRACT

Nemaline myopathy (NM) is a genetically and clinically heterogeneous muscle disorder, defined by the presence of characteristic nemaline bodies on muscle biopsy. The disease has a wide spectrum of phenotypes, ranging from forms with neonatal onset and fatal outcome to asymptomatic forms. The neonatal form is severe and usually fatal. The clinical variability, with differing age of onset and severity of symptoms makes the diagnosis difficult during infancy. There is no curative treatment. L-tyrosine may prevent aspiration by reducing pharyngeal secretions and drooling. Most of the patients die from respiratory and cardiac failure. This article discusses a newborn infant who presented with generalized weakness and respiratory failure. Partial response to L-tyrosine treatment was noted. The case is worth presenting to remind clinicians of congenital myopathies in the differential diagnosis of floppy infant during neonatal period and to emphasize the importance of muscle biopsy in diagnosis.


Subject(s)
Muscle Fibers, Skeletal/pathology , Muscular Diseases/etiology , Myopathies, Nemaline/pathology , Respiratory Insufficiency/etiology , Fatal Outcome , Humans , Infant, Newborn , Male , Muscular Diseases/pathology , Myopathies, Nemaline/complications , Myopathies, Nemaline/drug therapy , Respiratory Insufficiency/pathology , Tyrosine/therapeutic use
10.
Mol Genet Genomic Med ; 1(3): 123-30, 2013 Sep.
Article in English | MEDLINE | ID: mdl-24498610

ABSTRACT

Considering that variability in immune response genes has been associated with susceptibility to leprosy and with disease severity, leprosy presents clinicopathological variants that are highly associated with the immune response, HLA-G has a well-recognized role in the modulation of the immune response, and polymorphisms at the 3' untranslated region (UTR) of the HLA-G gene may influence HLA-G production, we studied the polymorphic sites at the 3' UTR of the HLA-G gene in leprosy and their association with disease severity. We evaluated by sequencing analysis the allele, genotype, and haplotype frequencies of the 3' UTR HLA-G polymorphic sites (14-bpINDEL/+3003C-T/+3010C-G/+3027A-C/+3035C-T/+3142C-G/+3187A-G/+3196C-G) in 146 individuals presenting reactive leprosy from a highly endemic area, and associated with bacillary load and the type of reactive leprosy. A total of 128 healthy subjects were also studied. Allele, genotype, and haplotype frequencies for the 3' UTR HLA-G polymorphisms in leprosy patients did not differ from those observed in healthy donors. The +3187A allele was responsible for protection against the development of multibacillary leprosy in a dominant model (AA + AG)/GG, OR = 0.11, P = 0.018), and the +3187A allele and +3187A-A genotype were overrepresented in type II reactive leprosy reaction. The effect of genetic factors on leprosy susceptibility may be hidden by environmental components in highly endemic areas. The HLA-G + 3187A polymorphic site, which is related to unstable mRNA production, was associated with the development of polar forms of leprosy and reactive leprosy reaction.

11.
Phys Rev Lett ; 108(12): 126601, 2012 Mar 23.
Article in English | MEDLINE | ID: mdl-22540607

ABSTRACT

We report on theoretical studies of electronic transport in the archetypical molecular hybrid formed by DNA wrapped around single-walled carbon nanotubes (CNTs). Using a Green's function formalism in a π-orbital tight-binding representation, we investigate the role that spin-orbit interactions play on the CNT in the case of the helicoidal electric field induced by the polar nature of the adsorbed DNA molecule. We find that spin polarization of the current can take place in the absence of magnetic fields, depending strongly on the direction of the wrapping and length of the helicoidal field. These findings open new routes for using CNTs in spintronic devices.


Subject(s)
DNA/chemistry , Models, Chemical , Nanotubes, Carbon/chemistry , Electric Conductivity , Magnetic Fields
12.
Int J Tuberc Lung Dis ; 16(5): 618-24, 2012 May.
Article in English | MEDLINE | ID: mdl-22410415

ABSTRACT

OBJECTIVES: To estimate the probability of survival and to evaluate risk factors for death in a cohort of persons living with human immunodeficiency virus (PLHIV) who had started tuberculosis (TB) treatment. METHODS: A prospective cohort study was conducted between June 2007 and December 2009 with HIV-infected patients who had started anti-tuberculosis treatment in the State of Pernambuco, Brazil. Survival data were analysed using the Kaplan-Meier estimator, the log-rank test and the Cox model. Hazard ratios and their respective 95%CIs were estimated. RESULTS: Of a cohort of 2310 HIV-positive individuals, 333 patients who had commenced treatment for TB were analysed. The mortality rate was 5.25 per 10,000 person-years (95%CI 4.15-6.63). The probability of survival at 30 months was 74%. Risk factors for death in the study population were being female, age ≥30 years, having anaemia, not using highly active antiretroviral therapy (HAART) during treatment for TB and disseminated TB. Protective factors for death were a CD4 lymphocyte count >200 cells/mm(3) and treatment for TB having started in an out-patient clinic. CONCLUSIONS: The use of HAART can prevent deaths among HIV-TB patients, corroborating the efficacy of starting HAART early in individuals with TB.


Subject(s)
Antiretroviral Therapy, Highly Active/methods , HIV Infections/mortality , Tuberculosis/mortality , Adolescent , Adult , Aged , Anemia/epidemiology , Anemia/etiology , Antitubercular Agents/therapeutic use , Brazil/epidemiology , CD4 Lymphocyte Count , Cohort Studies , Female , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Proportional Hazards Models , Prospective Studies , Risk Factors , Sex Factors , Survival Analysis , Survival Rate , Tuberculosis/drug therapy , Tuberculosis/epidemiology , Young Adult
13.
Auton Neurosci ; 166(1-2): 47-53, 2012 Jan 26.
Article in English | MEDLINE | ID: mdl-22079748

ABSTRACT

Blood pressure variability (BPV) and baroreflex dysfunction may contribute to end-organ damage process. We investigated the effects of baroreceptor deficit (10 weeks after sinoaortic denervation - SAD) on hemodynamic alterations, cardiac and pulmonary remodeling. Cardiac function and morphology of male Wistar intact rats (C) and SAD rats (SAD) (n=8/group) were assessed by echocardiography and collagen quantification. BP was directly recorded. Ventricular hypertrophy was quantified by the ratio of left ventricular weight (LVW) and right ventricular weight (RVW) to body weight (BW). BPV was quantified in the time and frequency domains. The atrial natriuretic peptide (ANP), alpha-skeletal actin (α-skelectal), collagen type I and type III genes mRNA expression were evaluated by RT-PCR. SAD did not change BP, but increased BPV (11±0.49 vs. 5±0.3 mmHg). As expected, baroreflex was reduced in SAD. Pulmonary artery acceleration time was reduced in SAD. In addition, SAD impaired diastolic function in both LV (6.8±0.26 vs. 5.02±0.21 mmHg) and RV (5.1±0.21 vs. 4.2±0.12 mmHg). SAD increased LVW/BW in 9% and RVW/BW in 20%, and augmented total collagen (3.8-fold in LV, 2.7-fold in RV, and 3.35-fold in pulmonary artery). Also, SAD increased type I (~6-fold) and III (~5-fold) collagen gene expression. Denervation increased ANP expression in LV (75%), in RV (74%) and increased α-skelectal expression in LV (300%) and in RV (546%). Baroreflex function impairment by SAD, despite not changing BP, induced important adjustments in cardiac structure and pulmonary hypertension. These changes may indicate that isolated baroreflex dysfunction can modulate target tissue damage.


Subject(s)
Baroreflex/physiology , Hypertension, Pulmonary/physiopathology , Hypertrophy, Left Ventricular/physiopathology , Pressoreceptors/physiopathology , Pulmonary Artery/physiopathology , Animals , Autonomic Denervation/adverse effects , Autonomic Denervation/methods , Disease Models, Animal , Familial Primary Pulmonary Hypertension , Heart Ventricles/diagnostic imaging , Heart Ventricles/pathology , Heart Ventricles/physiopathology , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/pathology , Hypertrophy, Left Ventricular/etiology , Hypertrophy, Left Ventricular/pathology , Male , Pressoreceptors/injuries , Pressoreceptors/surgery , Pulmonary Artery/diagnostic imaging , Pulmonary Artery/pathology , Rats , Rats, Wistar , Ultrasonography
14.
Minerva Pediatr ; 63(6): 449-57, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22075799

ABSTRACT

AIM: We aimed to investigate intraoperative diagnosis rate of aganglionosis with hematoxylin eosin (HE) staining, to review the current diagnostic procedures in Hirschsprung disease (HD), to inquire the validity of enzyme staining in diagnosis of HD and to evaluate the utility of ret oncoprotein (RET) antibody for detecting ganglion cells (GC) in paraffin sections. METHODS: Two hundred and thirty three children who are suspected to have HD were included in this study. A total of 302 surgical procedures related to diagnosis and treatment of HD were performed. One to 19 samples (3.5 ± 2.91) per each case were examined with intraoperative pathological consultation. Although establishing primary diagnoses of HD by frozen sections (FS) examination and performing a one-step approach for treatment have been aimed, consecutive surgical operations were required in 30 cases (12.9%). One hundred and sixty three cases (70%) were male. Seventy eight cases (33.5%) were in neonatal period (mean=13.5 ± 9.7 days). Only 56 cases were older than 1 year. GC were absent in 137 of cases. Presence of GC with FS examination weren't decided and prior colostomies were performed in 18 cases (7.7%). RESULTS: There were no discrepancies between the FS diagnoses and final diagnoses of the cases except these children. Requisition of consecutive surgical procedures interestingly was lower in neonates than others (P=0.01). Because of long duration, technical difficulty and standardization problems; not only immune histochemical stains but also enzyme stains should not be prefer for demonstration of GC during surgery. CONCLUSION: We suppose that if one-step approach is desired, the intraoperative evaluation of HE staining FS by experienced pathologists is still gold standard in the diagnosis of HD.


Subject(s)
Hirschsprung Disease/diagnosis , Hirschsprung Disease/surgery , Proto-Oncogene Proteins c-ret/metabolism , Biomarkers/metabolism , Biopsy , Coloring Agents , Colostomy , Eosine Yellowish-(YS) , Female , Fluorescent Dyes , Hematoxylin , Hirschsprung Disease/pathology , Humans , Infant , Infant, Newborn , Intraoperative Period , Male , Paraffin Embedding , Proto-Oncogene Proteins c-ret/immunology , Reproducibility of Results , Retrospective Studies , Treatment Outcome
15.
Mol Cell Endocrinol ; 333(1): 78-84, 2011 Feb 10.
Article in English | MEDLINE | ID: mdl-21168472

ABSTRACT

Role of reactive oxygen species (ROS)/nitric oxide (NO) balance and renin-angiotensin system in mediating cardiac hypertrophy in hyperthyroidism was evaluated in an in vivo and in vitro experimental model. Male Wistar rats were divided into four groups: control, thyroid hormone, vitamin E (or Trolox, its hydrosoluble analogue), thyroid hormone+vitamin E. Angiotensin II receptor (AT1/AT2) gene expression, immunocontent of AT1/AT2 receptors, angiotensinogen, NADPH oxidase (Nox2), and nitric oxide synthase isoforms, as well as ROS concentration (hydrogen peroxide and superoxide anion) were quantified in myocardium. Thyroid hormone increased ROS and NO metabolites, iNOS, nNOS and eNOS isoforms and it was accompanied by cardiac hypertrophy. AT1/AT2 expression and the immunocontent of angiotensinogen and Nox2 were enhanced by thyroid hormone. Antioxidants reduced ROS levels, Nox2, AT1/AT2, NOS isoforms and cardiac hypertrophy. In conclusion, ROS/NO balance may play a role in the control of thyroid hormone-induced cardiac hypertrophy mediated by renin-angiotensin system.


Subject(s)
Cardiomegaly/pathology , Reactive Nitrogen Species/metabolism , Reactive Oxygen Species/metabolism , Renin-Angiotensin System/physiology , Thyroid Hormones/metabolism , Angiotensinogen/analysis , Animals , Blotting, Western , Cardiomegaly/metabolism , Cells, Cultured , Chromans/pharmacology , Hyperthyroidism/metabolism , Male , NADPH Oxidases/analysis , Nitric Oxide/analysis , Nitric Oxide Synthase/genetics , Polymerase Chain Reaction , Rats , Rats, Wistar , Receptor, Angiotensin, Type 1/genetics , Receptor, Angiotensin, Type 1/metabolism , Receptor, Angiotensin, Type 2/genetics , Receptor, Angiotensin, Type 2/metabolism , Receptors, Angiotensin/genetics , Thyroid Hormones/pharmacology , Vitamin E/pharmacology
16.
Basic Res Cardiol ; 105(3): 325-35, 2010 May.
Article in English | MEDLINE | ID: mdl-20155476

ABSTRACT

Although most of effects of Angiotensin II (Ang II) related to cardiac remodelling can be attributed to type 1 Ang II receptor (AT(1)R), the type 2 receptor (AT(2)R) has been shown to be involved in the development of some cardiac hypertrophy models. In the present study, we investigated whether the thyroid hormone (TH) action leading to cardiac hypertrophy is also mediated by increased Ang II levels or by change on AT(1)R and AT(2)R expression, which could contribute to this effect. In addition, we also evaluated the possible contribution of AT(2)R in the activation of Akt and in the development of TH-induced cardiac hypertrophy. To address these questions, Wistar rats were treated with thyroxine (T(4), 0.1 mg/kg BW/day, i.p.), with or without AT(2)R blocker (PD123319), for 14 days. Cardiac hypertrophy was identified based on heart/body weight ratio and confirmed by analysis of atrial natriuretic factor mRNA expression. Cardiomyocyte cultures were used to exclude the influence of TH-related hemodynamic effects. Our results demonstrate that the cardiac Ang II levels were significantly increased (80%, P < 0.001) as well as the AT(2)R expression (50%, P < 0.05) in TH-induced cardiac hypertrophy. The critical involvement of AT(2)R to the development of this cardiac hypertrophy in vivo was evidenced after administration of AT(2) blocker, which was able to prevent in 40% (P < 0.01) the cardiac mass gain and the Akt activation induced by TH. The role of AT(2)R to the TH-induced cardiomyocyte hypertrophy was also confirmed after using PD123319 in the in vitro studies. These findings improve understanding of the cardiac hypertrophy observed in hyperthyroidism and provide new insights into the generation of future therapeutic strategies.


Subject(s)
Angiotensin II Type 2 Receptor Blockers , Heart Diseases/chemically induced , Heart Diseases/prevention & control , Myocardium/pathology , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Thyroxine/adverse effects , Angiotensin II/physiology , Animals , Cells, Cultured , Disease Models, Animal , Heart Diseases/physiopathology , Hyperthyroidism/physiopathology , Hypertrophy/chemically induced , Hypertrophy/physiopathology , Hypertrophy/prevention & control , Imidazoles/pharmacology , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/pathology , Proto-Oncogene Proteins c-akt/physiology , Pyridines/pharmacology , Rats , Rats, Wistar , Receptor, Angiotensin, Type 1/physiology , Receptor, Angiotensin, Type 2/physiology , Signal Transduction/physiology
17.
J Physiol ; 583(Pt 1): 213-23, 2007 Aug 15.
Article in English | MEDLINE | ID: mdl-17540701

ABSTRACT

This study assessed the behaviour of angiotensin II (Ang II) receptors in an experimental hypothyroidism model in male Wistar rats. Animals were subjected to thyroidectomy and resting for 14 days. The alteration of cardiac mass was evaluated by total heart weight (HW), right ventricle weight (RVW), left ventricle weight (LVW), ratio of HW, RVW and LVW to body weight (BW) and atrial natriuretic factor (ANF) expression. Cardiac and plasma Ang II levels and serum T3 and T4 were determined. The mRNA and protein levels of Ang II receptors were investigated by RT-PCR and Western blotting, respectively. Functional analyses were performed using binding assays. T3 and T4 levels and the haemodynamic parameters confirmed the hypothyroid state. HW/BW, RVW/BW and LVW/BW ratios and the ANF expression were lower than those of control animals. No change was observed in cardiac or plasma Ang II levels. Both AT1/AT2 mRNA and protein levels were increased in the heart of hypothyroid animals due to a significant increase of these receptors in the RV. Experiments performed in cardiomyocytes showed a direct effect promoted by low thyroid hormone levels upon AT1 and AT2 receptors, discarding possible influence of haemodynamic parameters. Functional assays showed that both receptors are able to bind Ang II. Herein, we have identified, for the first time, a close and direct relation of elevated Ang II receptor levels in hypothyroidism. Whether the increase in these receptors in hypothyroidism is an alternative mechanism to compensate the atrophic state of heart or whether it may represent a potential means to the progression of heart failure remains unknown.


Subject(s)
Hypothyroidism/metabolism , Myocytes, Cardiac/metabolism , Receptor, Angiotensin, Type 1/metabolism , Receptor, Angiotensin, Type 2/metabolism , Angiotensin II/metabolism , Animals , Atrial Natriuretic Factor , Blood Pressure/physiology , Cells, Cultured , Gene Expression Regulation , Hypothyroidism/pathology , Male , Myocardium/metabolism , Myocardium/pathology , Myocytes, Cardiac/pathology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Random Allocation , Rats , Rats, Wistar , Thyroid Hormones/blood , Thyroidectomy
18.
Pflugers Arch ; 454(1): 75-81, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17206447

ABSTRACT

Increased thyroid hormone (TH) levels are known to induce cardiac hypertrophy. Some studies have provided evidence for a functional link between angiotensin II (ANG II) and transforming growth factor beta1 (TGF-beta1) in the heart, both being able to also induce cardiac hypertrophy. However, the contribution of this growth factor activated directly by TH or indirectly by ANG II in cardiac hypertrophy development remains unknown. To analyze the possible role of TGF-beta1 in cardiac hypertrophy induced by TH and also to evaluate if the TGF-beta1 effect is mediated by ANG II receptors, we employed Wistar rats separated into control, hypothyroid (hypo) and hyperthyroid (T4 - 10) groups combined or not with ANG II receptor blockers (losartan or PD123319). Serum levels of T3 and T4, systolic pressure and heart rate confirmed the thyroid state of the groups. The T4 - 10 group presented a significant increase in cardiac TGF-beta1 levels; however, TGF-beta1 levels in the hypo group did not change in relation to the control. Inhibition of the increase in cardiac TGF-beta1 levels was observed in the groups treated with T4 in association with losartan or PD123319 when compared to the T4 - 10 group. These results demonstrate for the first time the TH-modulated induction of cardiac TGF-beta1 in cardiac hypertrophy, and that this effect is mediated by ANG II receptors.


Subject(s)
Cardiomegaly/chemically induced , Cardiomegaly/metabolism , Receptor, Angiotensin, Type 1/metabolism , Receptor, Angiotensin, Type 2/metabolism , Thyroxine , Transforming Growth Factor beta1/metabolism , Animals , Blood Pressure , Cardiomegaly/pathology , Cardiomegaly/physiopathology , Heart Rate , Hyperthyroidism/chemically induced , Hyperthyroidism/complications , Hyperthyroidism/physiopathology , Hypothyroidism/complications , Hypothyroidism/physiopathology , Myocardium/metabolism , Myocardium/pathology , Organ Size , RNA, Messenger/metabolism , Rats , Rats, Wistar , Thyroxine/blood , Transforming Growth Factor beta1/genetics , Triiodothyronine/blood
19.
Arq Bras Cardiol ; 78(2): 172-80, 2002 Feb.
Article in English, Portuguese | MEDLINE | ID: mdl-11887193

ABSTRACT

OBJECTIVE: To assess the effects of weight reduction with 10mg of sibutramine or placebo on blood pressure during 24 hours (ambulatory blood pressure monitoring), on left ventricular mass, and on antihypertensive therapy in 86 obese and hypertensive patients for 6 months. METHODS: The patients underwent echocardiography, ambulatory blood pressure monitoring, and measurement of the levels of hepatic enzymes prior to and after treatment with sibutramine or placebo. RESULTS: The group using sibutramine had a greater weight loss than that using placebo (6.7% versus 2.5%; p<0.001), an increase in heart rate (78.3 +/- 7.3 to 82 +/- 7.9 bpm; p=0.02), and a reduction in the left ventricular mass/height index (105 +/- 29.3 versus 96.6 +/- 28.58 g/m; p=0.002). Both groups showed similar increases in the levels of alkaline phosphatase and comparable adjustments in antihypertensive therapy; blood pressure, however, did not change. CONCLUSION: The use of sibutramine caused weight loss and a reduction in left ventricular mass in obese and hypertensive patients with no interference with blood pressure or with antihypertensive therapy.


Subject(s)
Appetite Depressants/therapeutic use , Cyclobutanes/therapeutic use , Hypertension/physiopathology , Obesity/drug therapy , Antihypertensive Agents/therapeutic use , Appetite Depressants/pharmacology , Blood Pressure/drug effects , Cyclobutanes/pharmacology , Double-Blind Method , Drug Interactions , Female , Heart Rate/drug effects , Heart Ventricles/drug effects , Humans , Hypertension/drug therapy , Hypertrophy, Left Ventricular/drug therapy , Male , Prospective Studies , Weight Loss/drug effects
20.
Arq. bras. cardiol ; 78(2): 172-180, Feb. 2002. tab, graf
Article in Portuguese, English | LILACS | ID: lil-303902

ABSTRACT

OBJECTIVE: To assess the effects of weight reduction with 10mg of sibutramine or placebo on blood pressure during 24 hours (ambulatory blood pressure monitoring), on left ventricular mass, and on antihypertensive therapy in 86 obese and hypertensive patients for 6 months. METHODS: The patients underwent echocardiography, ambulatory blood pressure monitoring, and measurement of the levels of hepatic enzymes prior to and after treatment with sibutramine or placebo. RESULTS: The group using sibutramine had a greater weight loss than that using placebo (6.7 percent versus 2.5 percent; p<0.001), an increase in heart rate (78.3±7.3 to 82±7.9 bpm; p=0.02), and a reduction in the left ventricular mass/height index (105±29.3 versus 96.6±28.58 g/m; p=0.002). Both groups showed similar increases in the levels of alkaline phosphatase and comparable adjustments in antihypertensive therapy; blood pressure, however, did not change. CONCLUSION: The use of sibutramine caused weight loss and a reduction in left ventricular mass in obese and hypertensive patients with no interference with blood pressure or with antihypertensive therapy


Subject(s)
Humans , Male , Female , Appetite Depressants , Cyclobutanes , Hypertension , Obesity , Antihypertensive Agents , Appetite Depressants , Blood Pressure , Cyclobutanes , Double-Blind Method , Heart Rate , Heart Ventricles , Hypertension , Prospective Studies , Weight Loss
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