Determination of the effects of pulmonary arterial hypertension and therapy on the cardiovascular system of rats by impedance cardiography

Aim

To evaluate the effects of bosentan, sildenafil, and combined therapy on the cardiovascular system using impedance cardiography (ICG) in rats with monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH).

Methods

Seventy male Wistar-albino rats were randomized into five groups. A single dose of MCT was given to all rats, except to the control group. After 4 weeks, bosentan, sildenafil, and combined treatment was started and lasted for 3 weeks. The last group that developed PAH did not receive any medication. Echocardiographic evaluation was performed to determine the PAH development. Thoracic fluid content index (TFCI), stroke volume index (SI), heart rate (HR), cardiac index (CI), and myocardial contractility index (IC) were determined. All procedures were performed at the baseline and after 4 and 7 weeks.

Results

Echocardiographic parameters showed that the all MCT-injected rats developed PAH. There were no significant inter- and intra-group differences in TFCI, SI, and IC (P > 0.05), but at the 7th week, CI value in the sildenafil-treated PAH rats was significantly higher than in other groups and HR of PAH rats with combined therapy was significantly lower than in other groups.

Conclusion

PAH did not have an effect on LV function of rats, or if it did, the effect was compensated by physiological processes. Also, sildenafil treatment deteriorated the LV cardiac index.Pulmonary arterial hypertension (PAH) is a chronic lung disease characterized by increased pulmonary artery pressure, pulmonary vascular damage, and medial hypertrophy of pulmonary arterioles, leading to right ventricular (RV) hypertrophy, RV failure, and eventually death (1). The monocrotaline (MCT)-induced model of PAH is the most used model in rats. MCT is a pyrrolizidine alkaloid from the plant Crotalaria spectabilis. A single injection of MCT results in injury to the vascular endothelium of the lung, pulmonary hypertension, and RV hypertrophy and failure within 3 or 4 weeks (2-5).A key feature of PAH is deregulation of important vasodilatory mechanisms in the pulmonary circulation, including increased expression of phosphodiesterase 5 (PDE5) (6). Acute and chronic experimental models of PAH use PDE5 inhibitor sildenafil to reduce pulmonary pressure (7,8). Another important PAH treatment method is by endothelin (ET) receptor antagonist bosentan (9). The endothelin system is highly active in PAH and causes sustained vasoconstriction of pulmonary arteries. It increases the autogenic activity of smooth muscle cells and fibroblasts in the pulmonary vessel wall, thereby decreasing the lumen of pulmonary vessels and also contributing to increased pulmonary vascular resistance (10,11). It is also known that ET receptor expression in the RV myocardium increases due to PAH (12).Heart failure due to PAH can be identified by clinical symptoms that are linked to hemodynamic indices of right heart failure (3,13). Because of the major differences between left and right heart hemodynamics and potentially different responses to pressure overload, the data obtained for RV myocardium do not have to be applicable to the left ventricle (LV). In addition, although chronic pulmonary hypertension selectively overloads the RV, there also manifests LV dysfunction (14). However, hemodynamic indices of the left heart and treatment effects on them cannot be identified in this situation. The aim of this study is to evaluate the effects of PAH and bosentan, sildenafil, and combined treatments on the LV hemodynamic parameters by impedance cardiography (ICG) in rats with MCT-induced PAH.     

Unexpected foreign body in the bladder of a spinal cord injured patient: A case report

Context: Bladder dysfunction is common in patients with spinal cord injuries. Clean intermittent catheterization is a preferred method of neurogenic bladder management among spinal cord injured patients. Some complications may occur due to the use of clean intermittent catheterization.

Findings: In this report, we presented a case with an unexpected foreign body detected in the bladder of a patient who used to perform clean intermittent catheterization for her neurogenic bladder management, to our knowledge, which has not been reported in the literature so far.

Conclusion/Clinical Relevance: In this case report, we want to emphasis the importance of different kind of foreign bodies remaining in the bladder during clean intermittent catheterization.     

Assessment of the results of a three‐year program for National Standardization and Quality Improvement of Medical Laboratories on Drug of Abuse Testing by the Ministry of Health in Turkey

The aim of this study is to assess the results of inspections in the last three years of drug abuse testing in medical laboratories according to the latest regulations in Turkey. The on‐site inspections of medical laboratories for drugs abuse testing performed in Alcohol and Drug Addiction Treatment Centers during 2014–2016 are described, and laboratory processes and performance evaluated. The performance of 35 laboratories in 2014, 62 laboratories in 2015, and 94 laboratories in 2016 were scored as the sum of the scores for all answers on the inspection form. An inspected laboratory was considered to have an unconformity if the total score was less than 2/3 of maximum score. The total scores of inspections and the number of laboratories with between years were compared using one‐way analysis of variance and slope Chi‐square for trend test, respectively. Total scores increased statistically significantly from 35.9 ± 16.2 in 2014, to 43.5 ± 16.3 in 2015 and 49.1 ± 1.3 in 2016 (p < 0.001). The laboratories with unconformities decreased statistically significantly from 57% in 2014 to 37% in 2015 and 22% in 2016 (p < 0.001). The published legislation and the inspections contributed to national standardization and improved quality of service in medical laboratories for drug abuse testing.     

Protective effects of a calcium channel blocker on apoptosis in thymus of neonatal STZ-diabetic rats

Streptozotocin (STZ) is known to induce insulin-dependent diabetes in experimental animals. In STZ-induced diabetes, atrophy of the thymus is caused by elevated intracellular calcium levels leading to apoptosis. Hyperglycemia is known to result in a decrease in numbers of T cells in the thymus and circulation. Intracellular calcium levels increase in diabetic animals after induction by STZ. Hyperglycemia inhibits Ca2+-ATPase and increases intracellular calcium levels. We have investigated apoptosis in thymus tissue of neonatal STZ (n-STZ)-diabetic rats and the effects of isradipine as a calcium channel blocker (CCB) on apoptosis. Five groups of newborn Wistar rats were used. On the second day after birth, 100 mg/kg STZ was given i.p. to the first two groups. The first group was n-STZ diabetic. To the second group, starting from the 12th week, 5 mg/kg/day isradipine (i.p) was given for 6 weeks. To the third group, the same dose of isradipine was given on the second day, followed by STZ treatment. The fourth group was non-diabetic and treated with 5 mg/kg/day isradipine for six weeks. The fifth group consisted of non-diabetic rats. To the sixth group, dexamethasone (5 mg/kg i.p.) was given to adult rats. For detection of apoptotic cells in paraffin-embedded thymus sections, the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay was used. The DNA ladder method was performed for analysis of DNA fragmentation. In the isradipine-treated non-diabetic group, typical apoptotic banding patterns were found, whereas thick bands between 123 and 246 bp length were found in the n-STZ- and n-STZ+isradipine-treated groups. More apoptotic cells were observed in the thymus of isradipine-treated, n-STZ-treated and n-STZ+isradipine-treated groups when compared with the non-diabetic control and isradipine+n-STZ-treated groups. In conclusion, we observed that long-term STZ diabetes results in apoptosis in the thymus. We also found that isradipine administered before STZ has protective effects against apoptosis, whereas isradipine alone induces apoptosis.     

Clinical findings and HER-2/neu gene amplification status of breast carcinoma patients

The study group was derived from the archival materials of 48 invasive intraductal breast cancer patients who had undergone partial mastectomy/ axillary dissection. All patients included in the study had clinically T1-2N0M0 invasive ductal carcinoma. To detect HER-2/neu status, fluorescent in situ hybridization was performed using a HER-2/neu locus-specific probe. Signals were counted and patients were classified in three groups according to signal ratios: signal ratio <2, group 1 (n=31); signal ratio 2-4, group 2 (n=11); signal ratio >4, group 3 (n=6). Ratios of axillary metastatic lymph nodes to dissected total lymph nodes were 17%, 23% and 83% in groups 1, 2 and 3 respectively (P=0.003). The number of metastatic axillary lymph nodes, and the ratio of microscopic metastatic lymph nodes were highest in group 3 (P=0.001 and P=0.008, respectively). No significant difference was observed between groups for distant metastasis in a 5-year follow-up period. Signal ratios decreased with estrogen receptor expression (P=0.03). Histopathologically, an irregular growth pattern of the tumor was observed in 100% of the patients in group 3, and in 54% and 60% in groups 1 and 2, respectively (P=0.04). Lymphovascular invasion of the tumor was significantly higher in group 3 compared to the other two groups (P=0.01). The extensive intraductal component ratio was the highest in group 3 (P=0.04). The appearance of desmoplastic reaction and lymphocyte infiltration did not show significant difference between the groups. Our results show that HER-2/neu signal ratio increases with lymphovascular invasion, an extensive intraductal component, irregular growth pattern and axillary metastasis in clinically T1-2N0M0 invasive ductal carcinoma of the breast.     

A new marker for myocardial injury in carbon monoxide poisoning: T peak–T end

ObjectivesCarbon monoxide (CO) poisoning frequently affects repolarization, resulting in abnormal electrocardiography findings. The goal of this study was to examine the effect of CO poisoning on the novel transmyocardial repolarization parameters T peak–T end (Tp-e), Tp-e dispersion, and Tp-e/QT and the relationship of these parameters to myocardial injury (MI).MethodsThis prospective study included 94 patients with CO poisoning and 40 healthy controls. Participants received an electrocardiography and had their blood drawn at admission and 6 and 24 hours after admission. The QT, Tp-e, Tp-e dispersion, and the Tp-e/QT ratio were calculated. Myocardial injury was determined based on an elevation in troponin any time during the first 24 hours. The patients were divided into 2 subgroups: those with and without MI.ResultsT peak–T end, Tp-e dispersion, and the Tp-e/QT ratio were higher at admission than after 6 and 24 hours of hospitalization and were higher than the control group (P < .001). There was a correlation between the carboxyhemoglobin level at admission and Tp-e and Tp-e dispersion (P < .001). The MI subgroup (n = 14) had a higher Tp-e at admission than did the non-MI subgroup (n = 80) (96 [11] milliseconds vs 87 [12] milliseconds, P = .03). There were no any significant differences in the Tp-e dispersion or the Tp-e/QT ratio between the 2 MI subgroups. Receiver operating characteristic analysis showed that a Tp-e cutoff value for MI of 91.5 milliseconds had a sensitivity of 72.7% and a specificity of 67.2%.ConclusionTransmyocardial repolarization parameters indicative of arrhythmia were prolonged in patients with CO poisoning. T peak–T end was associated with MI.     

Comparison of clinical assessments with computerized tomography pulmonary angiography results in the diagnosis of pulmonary embolism

Pulmonary embolism (PE) is difficult to diagnose. We investigated the relationship between computed tomography pulmonary angiography (CTPA) with clinical assessments and thrombus localization. 56 patients with the suspicion of PE; 27 male, 29 female were included. They were evaluated by empirical and Wells clinical assessments, tested with D-Dimer. According to the combination of both CTPA was performed where necessary (if one of the clinical assessments was high or intermediate or those with low clinical probability and high D-Dimer) in the algorithm we used. CTPA was regarded as gold standard. Dyspnea, chest pain, tachypnea, crackles were the most common symptoms and signs in patients having PE. Recent surgery within the risk factors was significantly higher in the PE present group. PE was diagnosed in 31 (55.4%) patients with CTPA. According to the empirical assessment 20 (64.5%) of the patients had high, 10 (32.3%) had intermediate and 1 (3.2%) had low clinical probability within 31 PE present group, while with Wells scoring 8 (25.8%) had high, 17 (54.8%) had intermediate and 6 (19.4%) had low clinical probability. Sensitivity of the empirical assessment and Wells scoring was 97%, 80% while the specificity was 16%, 68% respectively. Positive and negative predictive values of empirical assessment were 59%, 80% and these values of Wells scoring were 76%, 73% respectively. Thrombus was localized in main pulmonary arteries in 45.8% of patients with high clinical probability according to the empirical assessment. With Wells scoring in 45.5% of the high probability patients and only in 4.3% of the low probability patients thrombus was there. PE can be diagnosed noninvasively. Since PE can easily be underdiagnosed, empirical assessment which is more sensitive will be appropriate. There is a significant correlation between clinical assessments and presence of PE in CTPA. As the severity of clinical assessment increases, thrombus settles more proximal.     

Relationship between non-steroidal anti-inflammatory drug use and Helicobacter pylori infection in bleeding or uncomplicated peptic ulcers: A case-control study

BACKGROUND AND AIMS: Non-steroidal anti-inflammatory drug (NSAID) use has been closely associated with an increased risk of bleeding peptic ulcers, while the prevalence of Helicobacter pylori infection has been reported to be lower in bleeding ulcers than in non-bleeding ones. However, whether an interaction exists between NSAID use and H. pylori infection has not clearly been elucidated yet. The aims of this study were to determine the frequency of NSAID use and H. pylori infection, to predict risk factors in bleeding peptic ulcers and to determine whether NSAID use and H. pylori infection interact with each other. METHODS: Ninety-six patients with bleeding ulcer were included in the study. The control group consisted of 106 patients with non-bleeding ulcer. Data were analyzed by using the chi-squared test, Fisher's exact test and logistic regression analysis with or without interaction term (H. pylori by NSAID). RESULTS: Non-steroidal anti-inflammatory drug use was significantly more common in patients with bleeding ulcers than in controls (79.2 vs 38.7%, unadjusted odds ratio (OR): 6.02, 95% confidence interval (CI): 3.21-11.29). The frequency of the H. pylori infection was significantly lower in patients with bleeding ulcers than in controls (66.7 vs 89.6%, unadjusted OR: 0.23, 95% CI: 0.10-0.49). In the logistic regression analysis with the interaction term, male sex (adjusted OR: 3.70, 95% CI: 1.65-8.29), multiplicity of ulcers (adjusted OR: 4.10, 95% CI: 1.02-16.45) and NSAID use (adjusted OR: 33.87, 95% CI: 4.36-262.97) were independent risk factors for bleeding ulcers. There was a negative interaction between H. pylori and NSAID use (adjusted OR: 0.09, 95% CI: 0.01-0.83). CONCLUSIONS: The negative interaction between the two variables suggests that the presence of H. pylori is associated with a lower risk of bleeding in ulcer patients taking NSAIDs.     

Increased pleural fluid adenosine deaminase in brucellosis is difficult to differentiate from tuberculosis

Pleural involvement in brucellosis is very rare. Current knowledge on brucella pleuritis is limited to a few case studies, and pleural adenosine deaminase (ADA) in brucellosis has not been studied previously. We report the pleural fluid characteristics, including ADA, of two cases with brucella pleurisy. Analysis of the pleural fluids revealed exudative effusions with increased ADA level, decreased glucose concentration, and lymphocyte predominance. The similarity with tuberculous pleurisy was remarkable. We suggest that brucellosis should be considered in the differential diagnosis of tuberculosis, especially in regions endemic for both diseases.