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BACKGROUND AND AIM: Diffuse malignant peritoneal mesothelioma (DMPM) and peritoneal carcinomatosis (PC) have similar imaging in computer tomography (CT). We aimed to distinguish them. METHODS: Computer tomography findings were evaluated in 48 DMPM and 47 PC for the peritoneal, mesenteric, omentum, lymph nodes, viscera infiltration, ascites and pleural plaques. RESULTS: Two groups had no difference in terms of thickness, clinical manifestation, diameter of lymph nodes, ascites, and viscera infiltration. But they showed differences in the following: Ratio of asbestos exposure in DMPM group was higher. Smooth and irregular peritoneal thickening were more seen in DMPM group; peritoneal nodules were more commonly detected in PC group. Forty-eight cases of peritoneum in DMPM showed mild enhanced, while 14 patients in PC showed severe enhanced. Nodular type of omentum was more common in PC group than in DMPM group; omental cake was more commonly detected in DMPM group. Mesentery involvement was more commonly seen in DMPM group. Location of enlarged lymph nodes in cardiophrenic region was more frequently identified in DMPM, whereas location of enlarged lymph nodes in retroperitoneal region was more frequently identified in PC. Lymph nodes fusion was more frequently visualized in PC. Fixation of the intestinal wall was more common in DMPM. Pleural plaque was more common in DMPM. PC had distant metastasis except primary foci and peritoneum. In PC, tumor origins were ovary in 10, digestive system in 21, breast in one. CONCLUSION: Using a combination of CT findings may increase our ability to distinguish PC from DMPM.
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Carcinoma/diagnóstico por imagem , Mesotelioma/diagnóstico por imagem , Neoplasias Peritoneais/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Carcinoma/patologia , Diagnóstico Diferencial , Feminino , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Masculino , Mesentério/diagnóstico por imagem , Mesentério/patologia , Mesotelioma/patologia , Pessoa de Meia-Idade , Omento/diagnóstico por imagem , Omento/patologia , Neoplasias Peritoneais/patologia , Peritônio/diagnóstico por imagem , Peritônio/patologia , Estudos RetrospectivosRESUMO
OBJECTIVE: The aim of this study was to determine which computed tomography (CT) findings were useful in differentiating malignant peritoneal mesothelioma (MPM) and tuberculous peritonitis (TBP). METHODS: CT scans performed in 53 patients with MPM and 27 patients with TBP confirmed by pathology were retrospectively reviewed. The CT findings were evaluated for the morphologic appearance of ascites, peritoneum, mesenterium and omentum involvement, enlarged lymph nodes, solid abdominal viscera infiltration and metastases, and thoracic changes. The Pearson χ (2) test was used to compare differences between groups. RESULTS: Patients in both groups displayed a high proportion of peritoneum and mesenterium thickening. However, there were no obvious differences observed for ascites or swollen lymph nodes. There were significant differences in the following aspects between the two groups: (1) smooth peritoneal thickening was more frequent in patients with TBP, while irregular thickening was more frequently observed in patients with MPM; (2) caked omentum stratification was more common in patients with MPM; (3) mesentery involvement was less commonly observed in patients with TBP; (4) abdominal viscera infiltration and pleural plaques were more common in patients with MPM (46/53 and 48/53, respectively) than in those with TBP (0/27 and 0/27); and (5) more patients in the TBP group (14/27) displayed pleural effusion, and extraperitoneal tuberculosis was more common in patients with TBP (20/27). CONCLUSION: Although most CT findings analyzed are observed in both diseases, each disease has its own several unique characteristics. Therefore, using a combination of CT findings may increase our ability to distinguish TBP from MPM.
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Neoplasias Pulmonares/diagnóstico por imagem , Mesotelioma/diagnóstico por imagem , Neoplasias Peritoneais/diagnóstico por imagem , Peritonite Tuberculosa/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Mesotelioma Maligno , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Thyroid dysfunction is common in individuals with diabetes mellitus (DM) and may contribute to the associated cardiac dysfunction. However, little is known about the extent and pathophysiological consequences of low thyroid conditions on the heart in DM. DM was induced in adult female Sprague Dawley (SD) rats by injection of nicotinamide (N; 200 mg/kg) followed by streptozotocin (STZ; 65 mg/kg). One month after STZ/N, rats were randomized to the following groups (N = 10/group): STZ/N or STZ/N + 0.03 µg/mL T3; age-matched vehicle-treated rats served as nondiabetic controls (C). After 2 months of T3 treatment (3 months post-DM induction), left ventricular (LV) function was assessed by echocardiography and LV pressure measurements. Despite normal serum thyroid hormone (TH) levels, STZ/N treatment resulted in reductions in myocardial tissue content of THs (T3 and T4: 39% and 17% reduction versus C, respectively). Tissue hypothyroidism in the DM hearts was associated with increased DIO3 deiodinase (which converts THs to inactive metabolites) altered TH transporter expression, reexpression of the fetal gene phenotype, reduced arteriolar resistance vessel density, and diminished cardiac function. Low-dose T3 replacement largely restored cardiac tissue TH levels (T3 and T4: 43% and 10% increase versus STZ/N, respectively), improved cardiac function, reversed fetal gene expression and preserved the arteriolar resistance vessel network without causing overt symptoms of hyperthyroidism. We conclude that cardiac dysfunction in chronic DM may be associated with tissue hypothyroidism despite normal serum TH levels. Low-dose T3 replacement appears to be a safe and effective adjunct therapy to attenuate and/or reverse cardiac remodeling and dysfunction induced by experimental DM.
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Diabetes Mellitus Experimental/tratamento farmacológico , Terapia de Reposição Hormonal , Miocárdio/metabolismo , Hormônios Tireóideos/uso terapêutico , Animais , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Feminino , Hemodinâmica , Miocárdio/patologia , Ratos Sprague-Dawley , Hormônios Tireóideos/sangue , Hormônios Tireóideos/farmacologia , Remodelação Ventricular/efeitos dos fármacosRESUMO
BACKGROUND: Left ventricular (LV) remodeling following large transmural myocardial infarction (MI) remains a pivotal clinical issue despite the advance of medical treatment over the past few decades. Identification of new medications to improve the remodeling process and prevent progression to heart failure after MI is critical. Thyroid hormones (THs) have been shown to improve LV function and remodeling in animals post-MI and in the human setting. However, changes in underlying cellular remodeling resulting from TH treatment are not clear. METHODS: MI was produced in adult female Sprague-Dawley rats by ligation of the left descending coronary artery. L-thyroxine (T4) pellet (3.3 mg, 60 days sustained release) was used to treat MI rats for 8 weeks. Isolated myocyte shape, arterioles, and collagen deposition in the non-infarcted area were measured at terminal study. RESULTS: T4 treatment improved LV ±dp/dt, normalized TAU, and increased myocyte cross-sectional area without further increasing myocyte length in MI rats. T4 treatment increased the total LV tissue area by 34%, increased the non-infarcted tissue area by 41%, and increased the thickness of non-infarcted area by 36% in MI rats. However, myocyte volume accounted for only ~1/3 of the increase in myocyte mass in the non-infarct area, indicating the presence of more myocytes with treatment. T4 treatment tended to increase the total length of smaller arterioles (5 to 15 µm) proportional to LV weight increase and also decreased collagen deposition in the LV non-infarcted area. A tendency for increased metalloproteinase-2 (MMP-2) expression and tissue inhibitor of metalloproteinases (TIMPs) -1 to -4 expression was also observed in T4 treated MI rats. CONCLUSIONS: These results suggest that long-term T4 treatment after MI has beneficial effects on myocyte, arteriolar, and collagen matrix remodeling in the non-infarcted area. Most importantly, results suggest improved survival of myocytes in the peri-infarct area.
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Infarto do Miocárdio/patologia , Tiroxina/administração & dosagem , Remodelação Ventricular/efeitos dos fármacos , Animais , Arteríolas/patologia , Peso Corporal/efeitos dos fármacos , Colágeno/metabolismo , Ecocardiografia , Feminino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Tiroxina/sangue , Tri-Iodotironina/sangueRESUMO
OBJECTIVE: To evaluate the effects of heart rate (HR) on image quality and radiation dose of "triple rule-out" 320-row-640-slice multidetector computed tomography (MDCT) scan in patients with acute chest pain. METHODS: Retrospective analyses were performed for the clinical and imaging data of 38 cases with acute chest pain. All patients received 320-row-640-slice MDCT. Scanning program was electrocardiography-gated helical scan of full chest (160×0.5 mm). Based upon different heart rates, they were divided into A and B groups (A: n = 18, HR ≤ 65 bpm; B: n = 20, HR > 65 bpm). T he results of image quality and radiation dose of pulmonary artery, aorta and coronary artery between A and B group were evaluated respectively. T he subjective quality indicators of coronary artery were excellent, good, qualified and poor. RESULTS: (1) Overall quality assessment: the mean CT values of ascending aortic root, main pulmonary artery, right coronary artery and left coronary artery were (412 ± 79) HU, (381 ± 107) HU, (408 ± 79) HU, (406 ± 79) HU respectively; the contrast-noise ratio (CNR) of ascending aorta root was 12 ± 7; excellent stage of subjective quality assessment of coronary artery accounted for 66.13%, good and qualified stage 32.79% and poor stage 1.08%. T he mean radiation dose was 22 ± 3 mSv. (2) The mean CT value between A and B groups of ascending aortic root, main pulmonary artery, right coronary artery and left coronary artery, and CNR of ascending aortic root [(421 ± 62) HU vs (404 ± 93) HU, (402 ± 103) HU vs (362 ± 110) HU, (417 ± 62) HU vs (400 ± 92) HU, (417 ± 63) HU vs (397 ± 92) HU, 10 ± 3 vs 13 ± 8 respectively] were not statistically different (P > 0.05); the number of segments of excellent subjective quality assessment and evaluable (excellent, good and qualified) of coronary artery between A and B groups were statistically significant (P = 0.001, P = 0.019). Group A was better than Group B. But the number of diagnosed segments of Group B still accounted for 97.9%. T he radiation doses of two groups were 18 ± 6 and 26 ± 5 mSv respectively. Group B was significantly higher than Group A and significant difference existed between two values (P = 0.000). CONCLUSION: The "triple rule-out" 320-row-640-slice MDCT scan may acquire high quality images of aorta, pulmonary arteries and coronary arteries for both high and low HR groups. With a low contrast-medium dosage and patient radiation dose, it is ideal for an etiological diagnosis of acute chest pain. Reducing HR further improves image quality and lowers radiation dose.
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Dor no Peito/diagnóstico por imagem , Frequência Cardíaca , Tomografia Computadorizada Multidetectores , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doses de Radiação , Estudos RetrospectivosRESUMO
It has been shown that hypothyroidism may lead to delayed wound healing after experimental myocardial infarction (MI) in rats and increased infarct size in dogs. However, the long-term effect of hypothyroidism on left ventricular (LV) remodeling after MI has not been determined. Adult female Sprague-Dawley rats with and without surgical thyroidectomy (TX) were used in the study. Four weeks after TX, MI or sham MI was performed on TX and non-TX rats. Rats from all groups were examined 4 wk later. Four weeks after TX, hypothyroid-induced LV dysfunction was confirmed by echocardiography. In terminal experiments 4 wk after MI, TX sham-MI rats showed smaller hearts and impaired LV function compared with non-TX sham-MI controls. TX + MI rats showed smaller hearts with bigger infarct areas, higher LV end-diastolic pressures, and greater impairment of relaxation (-dP/dt) compared with non-TX MI rats. Relative changes after MI between TX and non-TX rats for most other hemodynamic and echocardiographic indexes were similar. These results suggest that preexisting hypothyroidism exaggerates post-MI remodeling and worsens LV function, particularly diastolic function.
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Hipotireoidismo/patologia , Hipotireoidismo/fisiopatologia , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Função Ventricular Esquerda/fisiologia , Remodelação Ventricular/fisiologia , Animais , Atrofia , Peso Corporal/fisiologia , Feminino , Hemodinâmica/fisiologia , Hipotireoidismo/complicações , Infarto do Miocárdio/complicações , Miocárdio/patologia , Tamanho do Órgão/fisiologia , Ratos , Ratos Sprague-Dawley , Hormônios Tireóideos/sangue , TireoidectomiaRESUMO
In the crystal structure of the title compound, C(52)H(36)Br(4)O(12)S(8)·CH(2)Cl(2), the thia-calix[4]arene unit adopts a 1,3-alternate conformation with an intra-molecular C-Hâ¯O hydrogen bond and four C-Hâ¯π inter-actions, with the four 4-MeC(6)H(4)SO(3) groups located alternately above and below the virtual plane (R) defined by the four bridging S atoms. The benzene ring of each 4-MeC(6)H(4)SO(3) unit is nearly perpendicular to one of the two neighboring phenol rings with inter-planar angles varying from 72.97â (13) to 78.70â (13)°, while the dihedral angles between the plane (R) and the phenol rings range from 83.04â (7) to 84.30â (9)°. In the supra-molecular structure, a solvent-bridged dimer composed of two main mol-ecules is formed by four inter-molecular C-Hâ¯O hydrogen bonds and locally creates an R(4) (4)(26) motif. Such dimers associate further into chains by inter-dimer C-Clâ¯O short contacts [Clâ¯O 3.182â (5)â Å]. Finally, these chains are linked into a two-dimensional network by a combination of inter-chain C-Brâ¯O inter-actions [Brâ¯O = 3.183â (3) and 2.966â (4)â Å] as well as C-Hâ¯O hydrogen bonds.
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Standard environmental features of the neonatal intensive care unit (NICU) may be stressful and not optimal for the maturation of very low birth weight premature infants (VLBWPIs). The present study investigated whether structured no-touch periods and reducing periods of light and sound stimulation may influence the developmental indices of VLBWPIs. Between June 2012 and June 2013, 60 consecutive VLBWPIs were equally apportioned to either an experimental or control group. The groups were statistically comparable with regard to sex ratio, gestational age and birth weight. Each group received routine nursing care, but infants in the experimental group were additionally cared for in a separate room with 3 h of rest every 8 h, and reduced light and sound from staff and instruments. At 7 and 14 days following birth, plasma insulin-like growth factor 1 (IGF-1) levels of the experimental group were significantly higher than that of the control group. Furthermore, at day 7 and 14, the body weight and crown-to-heel lengths were significantly increased in the experimental group compared with the control group. In summary, during the first 2 weeks following birth, the reduction of touch, sound and light stimulation in the NICU were associated with higher plasma IGF-1 levels and physical growth of VLBWPIs. These results may have implications for the better management of VLBWPIs in the NICU.
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OBJECTIVE: The aim of this study was to determine the impact of adaptive iterative dose reduction 3 D (AIDR3D) on the improvement of shoulder image quality in low-radiographic dose head and neck CT angiography (CTA). MATERIALS AND METHODS: Ninety patients who underwent CTA examination were randomly divided into two groups, namely group A (n = 45) and B (n = 45). Patients in group A were scanned under 120 kV and 300 mA, with images reconstructed by filtered back projection (FBP), and patients in group B were scanned under 80 kV and auto mA with images reconstructed by AIDR3D. Image quality was accessed by two experienced radiologists. The noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of common carotid artery (CCA) at C7 level, and radiation dosage were compared between the two groups. RESULTS: The score of CCA in group B was significantly higher than group A (p < 0.05), and there were no significant differences in the scores of carotid sinus and internal carotid artery between the two groups (p > 0.05). The score of intracranial artery in group B was lower than that of group A, however, the image quality in group B can meet the requirement of clinical diagnosis. The noise value of CCA at C7 level in group B was significantly lower than that of group A (p < 0.05). SNR and CNR values of CCA at C7 level in group B were significantly higher than those of group A (p < 0.05). Effective radiation dose in group B was significantly decreased compared with group A (p < 0.05). CONCLUSION: AIDR3D remarkably improved image quality in low-radiographic dose head and neck CTA over FBP, which made the low-dose CTA images meet the requirement of clinical diagnosis.
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Artéria Carótida Primitiva/diagnóstico por imagem , Angiografia por Tomografia Computadorizada/métodos , Cabeça/diagnóstico por imagem , Pescoço/diagnóstico por imagem , Idoso , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Doses de Radiação , Ombro , Razão Sinal-RuídoRESUMO
Thyroid hormone (TH) levels decline after a myocardial infarction (MI). Treatment with TH has been shown to improve left ventricular (LV) function in MI and other cardiovascular diseases, but the mechanisms are not clear. We have previously shown that TH can prevent myocyte apoptosis via Akt signaling in cultured neonatal rat cardiomyocytes. In this study, the effects of triiodo-L-thyronine (T3) on LV function and myocyte apoptosis after MI was examined in rats. After surgery, MI rats were treated with T3 for 3 days. Compared with sham-operated rats, MI rats showed significantly increased LV chamber dimension during systole and decreased LV function. T3 treatment increased LV +/-dP/dt but did not change LV chamber dimensions. MI rats also showed significantly increased myocyte apoptosis in the border area as assessed by DNA laddering and TUNEL assay. T3 treatment decreased the amount of DNA laddering, and reduced TUNEL positive myocytes in the border area, which was associated with phosphorylation of Akt at serine 473. These results suggest that T3 can protect myocytes against ischemia-induced apoptosis, which may be mediated by Akt signaling.
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Apoptose/efeitos dos fármacos , Infarto do Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Tri-Iodotironina/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Di-Iodotironinas/sangue , Ativação Enzimática/efeitos dos fármacos , Feminino , Hemodinâmica/efeitos dos fármacos , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/enzimologia , Isquemia Miocárdica/prevenção & controle , Miócitos Cardíacos/enzimologia , Tamanho do Órgão/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Tireotropina/sangue , Fatores de Tempo , Tri-Iodotironina/sangue , UltrassonografiaRESUMO
Background: We have shown that thyroid hormones (THs) are cardioprotective and can be potentially used as safe therapeutic agents for diabetic cardiomyopathy and permanent infarction. However, no reliable, clinically translatable protocol exists for TH treatment of myocardial ischemia-reperfusion (IR) injury. We hypothesized that modified low-dose triiodo-L-thyronine (T3) therapy would confer safe therapeutic benefits against IR injury. Methods: Adult female rats underwent left coronary artery ligation for 60 min or sham surgeries. At 2 months following surgery and T3 treatment (described below), the rats were subjected to functional, morphological, and molecular examination. Results: Following surgery, the rats were treated with T3 (8 µg/kg/day) or vehicle in drinking water ad libitum following IR for 2 months. Oral T3 significantly improved left ventricular (LV) contractility, relaxation, and relaxation time constant, and decreased beta-myosin heavy chain gene expression. As it takes rats ~6 h post-surgery to begin drinking water, we then investigated whether modified T3 dosing initiated immediately upon reperfusion confers additional improvement. We injected an intraperitoneal bolus of T3 (12 µg/kg) upon reperfusion, along with low-dose oral T3 (4.5 µg/kg/day) in drinking water for 2 months. Continuous T3 therapy (bolus + low-dose oral) enhanced LV contractility compared with oral T3 alone. Relaxation parameters were also improved compared to vehicle. Importantly, these were accomplished without significant increases in hypertrophy, serum free T3 levels, or blood pressure. Conclusions: This is the first study to provide a safe cardiac therapeutic window and optimized, clinically translatable treatment-monitoring protocol for myocardial IR using commercially available and inexpensive T3. Low-dose oral T3 therapy supplemented with bolus treatment initiated upon reperfusion is safer and more efficacious.
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OBJECTIVE: To investigate the beneficial effects of carvedilol on cardiomyocyte apoptosis and related gene expression after acute myocardial infarction (AMI). METHODS: Eighty-three female SD rats underwent ligation of left anterior descending coronary artery, and were randomly assigned to 2 groups 24 hours later: carvedilol (n = 40, 10 mg.kg(-1).d(-1)was administered via direct gastric gavage 24 hs after the ligation, Group C) and AMI control group (n = 43, normal saline of the same volume was given by gastric gavage, Group MI). Another 27 rats were used as sham operation group (Group S, administered with normal saline too). The rats of each group were killed and their hearts were taken out 48 hours and 4 weeks after observation respectively (MI-48 h, MI-4 week, C-48 h, C-4 week, S-48 h, and S-4 week subgroups). TUNEL and DNA gel electrophoresis were used to detect the cardiomyocyte apoptosis. Immunohistochemistry and Western blotting were used to detect the expression of bcl-2 and bax. RESULTS: The apoptotic indices of the infracted/scar, border and non-infarcted areas at any time-point of Group MI were all significantly higher than those of Group S (all P < 0.05). Only the apoptotic indices of the infracted/scar and border areas of the C-4 week subgroup were significantly lower than those of the MI-4 week subgroup (both P < 0.05), and were close to those of the non-infarcted area. DNA gel electrophoresis showed that the positive rate of Group S at any time-point were both 0, the positive rate of MI-48 h subgroup and C-48 h subgroup were both significantly higher than that of Group S (both P < 0.05) without significant difference between these 2 groups, and the positive rates of the MI-4 week subgroup and C-4 week subgroup were both 0. Immunohistochemistry showed that the bax gene expression was slightly to significantly increased in the infarcted/scar, border, and non-infarcted areas of the MI-48 h and MI-4 week subgroups. The bcl-2 expression was significantly increased only in the infracted area of the MI-48 h subgroup. The bcl-2 expression was slightly increased in the infracted and border areas of the C-48 h subgroup and the bax expression was significantly decreased in the infracted/scar area of the C-4 week subgroup. Western blotting showed that (1) the bcl-2 expression of the S-4 week subgroup was significantly higher than that of the S-48 h subgroup (P < 0.05), (2) the bcl-2 expression and bax expression of the MI-48 h subgroup were significantly higher than that of the S-48 h subgroup (P < 0.05 - 0.01), the bcl-2/bax ratio of the MI-48 h subgroup was significantly lower that that of the S-48 h subgroup, however, there were no significant differences in the bcl-2 and bax expression and bcl-2/bax ratio between the MI-4 week subgroup and S-48 h subgroup (all P > 0.05), and (3) There were no significant difference in the bcl-2 and bax expression between Group A and Group S (all P > 0.05), however, the bcl-2/bax ratios at the 2 time-points of Group C were both significantly higher than those of Group MI. CONCLUSION: Cardiomyocyte apoptosis occurs in the infarction/scar, border and non-infarcted areas after AMI. Prolonged treatment with carvedilol reduces cardiomyocyte apoptosis in the scar and border areas and increases the expression ratio of bcl-2/bax.
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Apoptose/efeitos dos fármacos , Carbazóis/farmacologia , Infarto do Miocárdio/fisiopatologia , Miócitos Cardíacos/efeitos dos fármacos , Propanolaminas/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteína X Associada a bcl-2/biossíntese , Antagonistas Adrenérgicos beta/farmacologia , Animais , Western Blotting , Carvedilol , Feminino , Imuno-Histoquímica , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Receptor fas/biossínteseRESUMO
OBJECTIVE: To compare the beneficial effects of Atenolol and Metoprolol on cardiomyocyte apoptosis and related gene expressions after acute myocardial infarction (AMI) in rats. METHODS: AMI model was established with the ligation of anterior descending coronary artery in 251 randomly selected female SD rats. Twenty-four hours after operation, the 124 survivors were randomly assigned to AMI control group (MI group, n = 43), Atenolol group (group A, 10 mg x kg(-1) d(-1), n = 39), and Metoprolol group (group B, 20 mg x kg(-1) x d(-1), n = 42). Sham operation group (group S, n = 27) was also established. Two subgroup (48 h subgroup and 4 weeks subgroup) was randomly divided in each group according to the time points. Drugs were given to each treatment group by gastric gavage 24 h after ligation. Cardiomyocyte apoptosis was detected with terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) and DNA ladder. Bcl-2, bax and caspase-3 genes were detected with immunohistochemistry and Western blot analysis. RESULTS: Compared with AMI control group, myocyte apoptosis rate (MAR) significantly decreased only in infarction area (P < 0.01) in group B. Bcl-2 expression was found to increase in myocytes of infarction, border and non-infarcted areas except for non-infarcted area of group A. Changes of the expressions of bax and caspase-3 was not significant. Four weeks after AMI, MAR was found to decrease significantly in scar, border and non-infarcted areas (P < 0.05, P < 0.01) in both group A and group B. No significant changes of bcl-2, bax and caspase-3 expressions was found except for a significant decrease of bax expression in non-infarcted area of group A. As indicated by Western blot, no significant change of the expressions of caspase-3, bcl-2 and bax were found in myocytes of group A and group B compared with AMI control group; however, bcl-2/bax ratio significantly increased to the same level of sham-operated group (P < 0.05). CONCLUSION: Both Atenolol and Metoprolol treatment can reduce cardiomyocyte apoptosis in infarction/scar, border and non-infarcted areas after AMI, mainly through the increase of bcl-2 expression and bcl-2/bax ratio.
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Antagonistas Adrenérgicos beta/farmacologia , Apoptose/efeitos dos fármacos , Atenolol/farmacologia , Metoprolol/farmacologia , Infarto do Miocárdio/patologia , Animais , Feminino , Miócitos Cardíacos/patologia , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/genética , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Proteína X Associada a bcl-2/biossíntese , Proteína X Associada a bcl-2/genéticaRESUMO
We previously determined that residual left ventricular (LV) myocardium of middle-aged rats had sex-related differences in regional tissue properties 4 weeks after a large myocardial infarction (MI). However, the impact of such differences on cardiac performance remained unclear. Therefore, our current study aimed to elucidate whether sex-related changes in MI-induced myocardial remodeling can influence cardiac function. A similar-sized MI was induced in 12-month-old male (M-MI) and female (F-MI) Sprague-Dawley rats by ligation of the left coronary artery. The cardiac function was monitored for 2 months after MI and then various LV parameters were compared between sexes. We found that although two sex groups had a similar pattern of MI-induced decline in LV function, F-MI rats had greater cardiac performance compared to M-MI rats, considering the higher values of EF (39.9 ± 3.4% vs. 26.7 ± 7.7%, P < 0.05), SW index (40.4 ± 2.1 mmHg ⢠mL/kg vs. 20.2 ± 3.3 mmHg ⢠mL/kg, P < 0.001), and CI (139.2 ± 7.9 mL/min/kg vs. 74.9 ± 14.7 mL/min/kg, P < 0.01). The poorer pumping capacity in M-MI hearts was associated with markedly reduced LV compliance and prolonged relaxation. On the tissue level, F-MI rats revealed a higher, than in M-MI rats, density of cardiac myocytes in the LV free wall (2383.8 ± 242.6 cells/mm(2) vs. 1785.7 ± 55.9 cells/mm(2), P < 0.05). The latter finding correlated with a lower density of apoptotic cardiac myocytes in residual LV myocardium of F-MI rats (0.18 ± 0.08 cells/mm(2) vs. 0.91 ± 0.30 cells/mm(2) in males, P < 0.01). Thus, our data suggested that F-MI rats had markedly attenuated decline in cardiac performance compared to males due to ability of female rats to better retain functionally favorable intrinsic myocardial properties.
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Coração/fisiopatologia , Infarto do Miocárdio/fisiopatologia , Miocárdio , Caracteres Sexuais , Função Ventricular Esquerda/fisiologia , Remodelação Ventricular/fisiologia , Animais , Vasos Coronários/fisiopatologia , Feminino , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Malignant peritoneal mesothelioma with invasion of the liver is an invariably fatal disease. We aimed to clarify the characteristics of malignant peritoneal mesothelioma cases with liver involvement. The clinical presentation, computed tomography images, and immunohistochemical and histopathological features of 5 patients with malignant peritoneal mesothelioma and liver involvement were evaluated. The diagnosis was established by imaging and immune profiles of the tumours. A review of 8 cases with primary or invading malignant mesothelioma in liver is presented. All 5 mesothelioma cases were asbestos-related. CT images of malignant peritoneal mesothelioma with the liver involvement typically showed that the lesion grew inside the liver along the capsule and was possibly accompanied by capsule breakthrough and extrahepatic infiltration. The tumours exhibited a common epithelioid appearance in all 5 patients and most cases revealed positive Cal, CK, and MC with negative CEA and HeP. Different from our findings, the review of literature revealed that most malignant mesothelioma of liver was due to primary intrahepatic malignant mesothelioma. Finally, we concluded that the diagnosis of malignant peritoneal mesothelioma cases with liver invasion is reliably achieved by the history of asbestos exposure, the characteristic CT imaging, and immune profiles of the tumours.
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BACKGROUND: A large body of evidence suggests that thyroid hormones (THs) are beneficial for the treatment of cardiovascular disorders. We have shown that 3 days of triiodo-L-thyronine (T3) treatment in myocardial infarction (MI) rats increased left ventricular (LV) contractility and decreased myocyte apoptosis. However, no clinically translatable protocol is established for T3 treatment of ischemic heart disease. We hypothesized that low-dose oral T3 will offer safe therapeutic benefits in MI. METHODS AND RESULTS: Adult female rats underwent left coronary artery ligation or sham surgeries. T3 (~6 µg/kg/day) was available in drinking water ad libitum immediately following MI and continuing for 2 month(s) (mo). Compared to vehicle-treated MI, the oral T3-treated MI group at 2 mo had markedly improved anesthetized Magnetic Resonance Imaging-based LV ejection fraction and volumes without significant negative changes in heart rate, serum TH levels or heart weight, indicating safe therapy. Remarkably, T3 decreased the incidence of inducible atrial tachyarrhythmias by 88% and improved remodeling. These were accompanied by restoration of gene expression involving several key pathways including thyroid, ion channels, fibrosis, sympathetic, mitochondria and autophagy. CONCLUSIONS: Low-dose oral T3 dramatically improved post-MI cardiac performance, decreased atrial arrhythmias and cardiac remodeling, and reversed many adverse changes in gene expression with no observable negative effects. This study also provides a safe and effective treatment/monitoring protocol that should readily translate to humans.
Assuntos
Arritmias Cardíacas/prevenção & controle , Infarto do Miocárdio/complicações , Tri-Iodotironina/administração & dosagem , Administração Oral , Animais , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Feminino , Imageamento por Ressonância Magnética , Infarto do Miocárdio/fisiopatologia , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Tri-Iodotironina/sangueRESUMO
Thyroid hormones (THs) play a pivotal role in regulating cardiovascular homeostasis. To provide a better understanding of the coordinated processes that govern cardiac TH bioavailability, this study investigated the influence of serum and cardiac TH status on the expression of TH transporters and cytosolic binding proteins in the myocardium. In addition, we sought to determine whether the administration of T(3) (instead of T(4)) improves the relationship between THs in serum and cardiac tissue and cardiac function over a short-term treatment period. Adult female Sprague Dawley rats were made hypothyroid by 7 weeks treatment with the antithyroid drug 6-n-propyl-2-thiouracil (PTU). After establishing hypothyroidism, rats were assigned to 1 of 5 graded T(3) dosages plus PTU for a 2-week dose-response experiment. Untreated, age-matched rats served as euthyroid controls. PTU was associated with depressed serum and cardiac tissue T(3) and T(4) levels, arteriolar atrophy, altered TH transporter and cytosolic TH binding protein expression, fetal gene reexpression, and cardiac dysfunction. Short-term administration of T(3) led to a mismatch between serum and cardiac tissue TH levels. Normalization of serum T(3) levels was not associated with restoration of cardiac tissue T(3) levels or cardiac function. In fact, a 3-fold higher T(3) dosage was necessary to normalize cardiac tissue T(3) levels and cardiac function. Importantly, this study provides the first comprehensive data on the relationship between altered TH status (serum and cardiac tissue), cardiac function, and the coordinated in vivo changes in cardiac TH membrane transporters and cytosolic TH binding proteins in altered TH states.
Assuntos
Hipotireoidismo/tratamento farmacológico , Hormônios Tireóideos/uso terapêutico , Animais , Modelos Animais de Doenças , Feminino , Coração/efeitos dos fármacos , Miocárdio/metabolismo , Ratos , Ratos Sprague-Dawley , Hormônios Tireóideos/sangue , Tiroxina/sangue , Tiroxina/uso terapêutico , Tri-Iodotironina/sangue , Tri-Iodotironina/uso terapêuticoRESUMO
INTRODUCTION: The expression of hundreds of genes is altered in response to left ventricular (LV) remodeling following large transmural myocardial infarction (MI). Thyroid hormone (TH) improves LV remodeling and cardiac performance after MI. However, the molecular basis is unknown. METHODS: MI was produced by ligation of the left anterior descending coronary artery in female SD rats. Rats were divided into the following groups: (1) Sham MI, (2) MI, and (3) MI+T4 treatment (T4 pellet 3.3 mg, 60 days release, implanted subcutaneously immediately following MI). Four weeks after surgery, total RNA was isolated from LV non-infarcted areas for microarray analysis using the Illumina RatRef-12 Expression BeadChip Platform. RESULTS: Signals were detected in 13,188 genes (out of 22,523), of which the expression of 154 genes were decreased and the expression of 200 genes were increased in MI rats compared with Sham MI rats (false discovery rate (FDR) <0.05). Compared to MI rats, T4 treatment decreased expression of 27 genes and increased expression of 28 genes. In particular, 6 genes down-regulated by MI and 12 genes up-regulated by MI were reversed by T4. Most of the 55 genes altered by T4 treatment are in the category of molecular function under binding (24) and biological processes which includes immune system process (9), multi-organism process (5) and biological regulation (19) nonexclusively. CONCLUSIONS: These results suggest that altered expression of genes for molecular function and biological process may be involved in the beneficial effects of thyroid hormone treatment following MI in rats.
Assuntos
Regulação da Expressão Gênica , Proteínas Musculares/biossíntese , Infarto do Miocárdio/metabolismo , Hormônios Tireóideos/metabolismo , Remodelação Ventricular , Animais , Feminino , Perfilação da Expressão Gênica/métodos , Infarto do Miocárdio/patologia , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Previous studies have shown gender differences in left ventricular remodeling after myocardial infarction. Results are varied, however, and reliable, comprehensive data for changes in cardiac myocyte shape are not available. METHODS: Young adult female and male Sprague-Dawley rats were used in this study and randomly assigned to the myocardial infarction and sham myocardial infarction groups. Myocardial infarction was produced by ligation of the left descending coronary artery. Four weeks after surgery, left ventricular echocardiography and hemodynamics were performed before isolating myocytes for size determination. RESULTS: In general, left ventricular functional changes after myocardial infarction were comparable. Females developed slightly, but significantly, more left ventricular hypertrophy than males, and this was reflected by the relative increases in left ventricular myocyte volume. In both males and females, however, myocyte hypertrophy was due exclusively to lengthening of myocytes with no change in myocyte cross-sectional area. CONCLUSIONS: This study demonstrates that post-myocardial infarction changes in LV function and myocyte remodeling are remarkably similar in young adult male and female rats.
Assuntos
Infarto do Miocárdio/patologia , Miócitos Cardíacos/patologia , Remodelação Ventricular , Animais , Modelos Animais de Doenças , Ecocardiografia , Feminino , Hemodinâmica , Masculino , Infarto do Miocárdio/fisiopatologia , Ratos , Ratos Sprague-Dawley , Fatores Sexuais , Função Ventricular EsquerdaRESUMO
BACKGROUND: MicroRNAs (miRNAs) have been shown to anticipate great cancer diagnostic potential. Recently, circulating miRNAs have been reported as promising biomarkers for various pathologic conditions. The objective of this study was to investigate the potential of serum miRNAs as novel biomarkers for hepatocellular carcinoma (HCC). METHODOLOGY/PRINCIPAL FINDINGS: This study was divided into four phases: (I) Ten candidate serum miRNAs were detected by using real-time RT-PCR, corresponding 10 HCC patients with chronic hepatitis B virus (HBV) infection and 10 age- and sex-matched healthy subjects. (II) Marker validation by real-time RT-PCR on HBV patients with (n = 48) or without HCC (n = 48), and healthy subjects (n = 24). (III) Marker detection by real-time RT-PCR in sera from another 14 HCC patients before and 1 month after surgical resection. (IV) We examined the correlation between the expressions of candidate serum miRNAs with clinical parameters of HCC patients. Although miR-222, miR-223 or miR-21 were significantly up- or down-regulated between HCC patients and healthy controls, no significant difference was observed in the levels of these miRNAs between HBV patients without and with HCC. MiR-122 in serum was significantly higher in HCC patients than healthy controls (p<0.001). More importantly, it was found that the levels of miR-122 were significantly reduced in the post-operative serum samples when compared to the pre-operative samples. Although serum miR-122 was also elevated in HBV patients with HCC comparing with those without HCC, the difference was at the border line (p = 0.043). CONCLUSIONS/SIGNIFICANCE: Our results suggest that serum miR-122 might serve as a novel and potential noninvasive biomarker for detection of HCC in healthy subjects, moreover, it might serve as a novel biomarker for liver injury but not specifically for detection of HCC in chronic HBV infection patients.