Effect of new thiazolidine derivatives LPSF/GQ-02 and LPSF/GQ-16 on atherosclerotic lesions in LDL receptor-deficient mice (LDLR−/−)

BackgroundAtherosclerotic cardiovascular disease is a chronic inflammatory condition. Thiazolidinediones (TZDs) are used to enhance sensitivity to insulin and have demonstrated a protective effect over a variety of cardiovascular markers and risk factors. Controversially, the TZDs are associated with the development of heart failure. Thus, lines of research have invested in the search for new molecules in order to obtain more selective and less harmful treatment alternatives for the pathogenesis of atherosclerosis and its risk factors.MethodsAnimals were fed a diet rich in fat for 10 weeks. In the last 2 weeks, animals received either pioglitazone, LPSF/GQ-02, or LPSF/GQ-16 daily through gavage. At the end of the treatment, blood was collected for biochemical analysis and the aortas were dissected for subsequent analyses.ResultsNo changes in the blood lipid profile were found following the use of the drugs in comparison to the control. However, the new thiazolidine derivatives were more efficient in improving insulin resistance in comparison to pioglitazone and the control group. Morphometric analyses revealed that neither pioglitazone nor LPSF/GQ16 led to satisfactory effects over atherosclerosis. However, LPSF/GQ-02 led to a reduction in area of the atherosclerotic lesions. Ultrastructural analyses revealed extensive degeneration of the endothelium and an increase in apoptotic cells in the subendothelial space following the use of pioglitazone and LPSF/GQ-16. However, LPSF/GQ-02 caused minimal cell alterations in the aortic endothelium. Regarding markers, endothelial nitric oxide synthase (eNOS) and matrix metalloproteinase 9 (MMP-9), LPSF/GQ-16, and pioglitazone exerted similar effects, increasing the expression of MMP-9, and had no effect on the expression of eNOS compared with the control group. On the other hand, LPSF/GQ-02 was effective in reducing the expression of MMP-9 and increased eNOS significantly.ConclusionsThe results suggest that the new thiazolidine derivative LPSF/GQ-02 is a promising candidate for the treatment of atherosclerosis.     

Stratification of complexity in congenital heart surgery: comparative study of the Risk Adjustment for Congenital Heart Surgery (RACHS-1) method, Aristotle basic score and Society of Thoracic Surgeons-European Association for Cardio- Thoracic Surgery (STS-EACTS) mortality score

Objective

To determine whether stratification of complexity models in congenital heart surgery (RACHS-1, Aristotle basic score and STS-EACTS mortality score) fit to our center and determine the best method of discriminating hospital mortality.

Methods

Surgical procedures in congenital heart diseases in patients under 18 years of age were allocated to the categories proposed by the stratification of complexity methods currently available. The outcome hospital mortality was calculated for each category from the three models. Statistical analysis was performed to verify whether the categories presented different mortalities. The discriminatory ability of the models was determined by calculating the area under the ROC curve and a comparison between the curves of the three models was performed.

Results

360 patients were allocated according to the three methods. There was a statistically significant difference between the mortality categories: RACHS-1 (1) - 1.3%, (2) - 11.4%, (3)-27.3%, (4) - 50 %, (P<0.001); Aristotle basic score (1) - 1.1%, (2) - 12.2%, (3) - 34%, (4) - 64.7%, (P<0.001); and STS-EACTS mortality score (1) - 5.5 %, (2) - 13.6%, (3) - 18.7%, (4) - 35.8%, (P<0.001). The three models had similar accuracy by calculating the area under the ROC curve: RACHS-1- 0.738; STS-EACTS-0.739; Aristotle- 0.766.

Conclusion

The three models of stratification of complexity currently available in the literature are useful with different mortalities between the proposed categories with similar discriminatory capacity for hospital mortality.     

Efficacy and safety of telmisartan, a selective AT1 receptor antagonist, compared with enalapril in elderly patients with primary hypertension. TEES Study Group

OBJECTIVE: To assess the antihypertensive efficacy and safety of the novel AT1 receptor antagonist, telmisartan, compared with that of enalapril in elderly patients with mild to moderate hypertension. DESIGN: A 26-week, multicenter, double-blind, parallel-group, dosage titration study. METHODS: A total of 278 patients aged > or = 65 years were randomized to eithertelmisartan or enalapril once a day. The telmisartan dosage was increased from 20 to 40-80 mg and that of enalapril from 5 to 10-20 mg at 4-week intervals until trough supine diastolic blood pressure was < 90 mmHg. After 12 weeks, hydrochlorothiazide at 12.5-25 mg once a day was added to the treatment regimen of those patients not controlled on monotherapy. RESULTS: Both treatments lowered blood pressure in a comparable and clinically meaningful manner. The adjusted mean changes from baseline in supine diastolic blood pressure at trough were -12.8 mmHg for telmisartan and -11.4 mmHg for enalapril (P = 0.074). Mean changes in supine systolic blood pressure were -22.1 mmHg for telmisartan and -20.1 mmHg for enalapril (P = 0.350). Overall, 63 and 62% of patients responded to telmisartan and enalapril, respectively, with a supine diastolic blood pressure of < 90 mmHg. Both regimens provided effective blood pressure lowering over the 24 h dosing interval, as determined by ambulatory blood pressure monitoring. Both regimens were well tolerated; however, patients on the enalapril regimen had more than double the incidence of treatment-related cough compared with those on the telmisartan regimen (16 versus 6.5%). CONCLUSIONS: These results demonstrate that telmisartan is well tolerated and is at least as effective as enalapril in treating elderly patients with mild to moderate hypertension.     

QUANTITATIVE REAL-TIME PCR (Q-PCR) FOR SPUTUM SMEAR DIAGNOSIS OF PULMONARY TUBERCULOSIS AMONG PEOPLE WITH HIV/AIDS

Objective: To assess quantitative real-time polymerase chain reaction (q-PCR) for the sputum smear diagnosis of pulmonary tuberculosis (PTB) in patients living with HIV/AIDS with a clinical suspicion of PTB. Method: This is a prospective study to assess the accuracy of a diagnostic test, conducted on 140 sputum specimens from 140 patients living with HIV/AIDS with a clinical suspicion of PTB, attended at two referral hospitals for people living with HIV/AIDS in the city of Recife, Pernambuco, Brazil. A Löwenstein-Jensen medium culture and 7H9 broth were used as gold standard. Results: Of the 140 sputum samples, 47 (33.6%) were positive with the gold standard. q-PCR was positive in 42 (30%) of the 140 patients. Only one (0.71%) did not correspond to the culture. The sensitivity, specificity and accuracy of the q-PCR were 87.2%, 98.9% and 95% respectively. In 39 (93%) of the 42 q-PCR positive cases, the CT (threshold cycle) was equal to or less than 37. Conclusion: q-PCR performed on sputum smears from patients living with HIV/AIDS demonstrated satisfactory sensitivity, specificity and accuracy, and may therefore be recommended as a method for diagnosing PTB.     

Non-flat audiograms in sensorineural hearing loss and speech perception

OBJECTIVE:

The audibility thresholds for the sound frequency of 137 upward- and downward-sloping audiograms showing sensorineural hearing loss were selected and analyzed in conjunction with speech recognition thresholds obtained from individuals seen at a public otolaryngology clinic to determine which frequencies in slope audiograms best represent speech recognition thresholds.

METHOD:

The linear regression model and mean square error were used to determine the associations between the threshold values.

RESULT:

The mean square error identified larger errors when using thresholds of 500, 1000, and 2000 Hz than when using audibility thresholds of 500, 1000, 2000, and 4000 Hz. The linear regression model showed a higher correlation (91%) between the audiogram thresholds for frequencies of 500, 1000, 2000, and 4000 Hz than for the frequencies of 500, 1000, and 2000 Hz (88%).

CONCLUSION:

Frequencies of 500, 1000, 2000, and 4000 Hz were the most significant in predicting the speech recognition threshold.     

Ankle-brachial index as a predictor of coronary disease events in elderly patients submitted to coronary angiography

OBJECTIVES:

To correlate the importance of the ankle-brachial index in terms of cardiovascular morbimortality and the extent of coronary arterial disease amongst elderly patients without clinical manifestations of lower limb peripheral arterial disease.

METHODS:

We analyzed prospective data from 100 patients over 65 years of age with coronary arterial disease, as confirmed by coronary angiography, and with over 70% stenosis of at least one sub-epicardial coronary artery. We measured the ankle-brachial index immediately after coronary angiography, and a value of <0.9 was used to diagnose peripheral arterial disease.

RESULTS:

The patients'' average age was 77.4 years. The most prevalent risk factor was hypertension (96%), and the median late follow-up appointment was 28.9 months. The ankle-brachial index was <0.9 in 47% of the patients, and a low index was more prevalent in patients with multiarterial coronary disease compared to patients with uniarterial disease in the same group. Using a bivariate analysis, only an ankle-brachial index of <0.9 was a strong predictive factor for cardiovascular events, thereby increasing all-cause deaths and fatal and non-fatal acute myocardial infarctions two- to three-fold.

CONCLUSION:

In elderly patients with documented coronary disease, a low ankle-brachial index (<0.9) was associated with the severity and extent of coronary arterial disease, and in late follow-up appointments, a low index was correlated with an increase in the occurrence of major cardiovascular events.     

Thermo and mechanical cycling and veneering method do not influence Y-TZP core/veneer interface bond strength

ObjectivesThe purpose of this study was to evaluate the influence of thermal and mechanical cycling and veneering technique on the shear bond strength of Y-TZP (yttrium oxide partially stabilized tetragonal zirconia polycrystal) core–veneer interfaces.Materials and methodsCylindrical Y-TZP specimens were veneered either by layering (n = 20) or by pressing technique (n = 20). A metal ceramic group (CoCr) was used as control (n = 20). Ten specimens for each group were thermal and mechanical cycled and then all samples were subjected to shear bond strength in a universal testing machine with a 0.5 mm/min crosshead speed. Mean shear bond strength (MPa) was analysed with a 2-way analysis of variance and Tukey's test (p < 0.05). Failure mode was determined using stereomicroscopy and scanning electron microscopy (SEM).ResultsThermal and mechanical cycling had no influence on the shear bond strength for all groups. The CoCr group presented the highest bond strength value (p < 0.05) (34.72 ± 7.05 MPa). There was no significant difference between Y-TZP veneered by layering (22.46 ± 2.08 MPa) or pressing (23.58 ± 2.1 MPa) technique. Failure modes were predominantly adhesive for CoCr group, and cohesive within veneer for Y-TZP groups.ConclusionsThermal and mechanical cycling, as well as the veneering technique does not affect Y-TZP core–veneer bond strength.Clinical significanceDifferent methods of veneering Y-TZP restorations would not influence the clinical performance of the core/veneer interfaces.     

Usefulness of cone‐beam CT in the evaluation of a spontaneously healed root fracture case

Horizontal root fractures (HRF) usually affect anterior teeth of male patients as a result of trauma. The consequences can be complex because of combined damage to different tissues, but it has been reported that root fractures undergo healing in majority cases. Diagnosis of HRF must be based on clinical findings, sensibility tests, and radiographic examination. The cone‐beam computed tomography (CBCT) has already been proven to be superior among other radiographic modalities for diagnostic imaging of root fractures. However, CBCT in these cases needs to be used in a careful manner, and only when the radiation exposure should be justified by the potential diagnostic benefits and improvement of the treatment results. This case report describes a case of spontaneously healed horizontal root fracture with displacement of the fragments and discusses the usefulness of CBCT in the follow‐up of root fractures cases.