Brazilian Journal of Medical and Biological Research
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Open Access journal
ISSN (Print) 0100-879X - ISSN (Online) 1414-431X
Published by SciELO [718 journals]
- Invasive pulmonary fungal infections in patients with connective tissue
disease: a retrospective study from northern China
Abstract: Invasive pulmonary fungal infection (IPFI) is a potentially fatal complication in patients with connective tissue disease (CTD). The current study aimed to uncover the clinical characteristics and risk factors of patients with IPFI-CTD. The files of 2186 CTD patients admitted to a single center in northern China between January 2011 and December 2013 were retrospectively reviewed. A total of 47 CTD patients with IPFI were enrolled into this study and assigned to the CTD-IPFI group, while 47 uninfected CTD patients were assigned to the control group. Clinical manifestations were recorded, and risk factors of IPFI were calculated by stepwise logistical regression analysis. Forty-seven (2.15%) CTD patients developed IPFI. Systemic lupus erythematosus patients were responsible for the highest proportion (36.17%) of cases with IPFI. Candida albicans (72.3%) accounted for the most common fungal species. CTD-IPFI patients had significantly elevated white blood cell count, erythrocyte sedimentation rate, C-reactive protein and fasting glucose values compared to controls (P<0.05). Cough, sputum and blood in phlegm were the most common symptoms. Risk factors of IPFI in CTD included maximum prednisone dose ≥30 mg/day within 3 months prior to infection, anti-microbial drug therapy, and interstitial pneumonia. CTD patients who have underlying interstitial pneumonia, prior prednisone or multiple antibiotics, were more likely to develop IPFI.
- Depression and diagnosis of neurocognitive impairment in HIV-positive
Abstract: Neurocognitive impairment (NCI) is frequently observed in patients infected with human immunodeficiency virus (HIV) and results from the compromise of subcortical brain structures by the virus. The manifestations of NCI range from asymptomatic impairment to dementia. In addition to cognitive impairment resulting from HIV infection, other factors such as depression are associated with the loss of cognitive functions. The aim of this study was to estimate the prevalence of NCI in HIV-positive patients in a city in southern Brazil and to establish possible associations for the prevalence of NCI with HIV-related and other risk factors. This cross-sectional study of HIV-positive outpatients was conducted in a specialized care service in the city of Pelotas in Southern Brazil. Sociodemographic data and HIV-related information were collected, and all patients underwent psychiatric and neurocognitive evaluations. The prevalence of NCI among the 392 patients was 54.1% when tracked using the IHDS (International HIV Dementia Scale) and 36.2% when the IHDS was associated with a battery of complementary tests. A bivariate analysis suggested an association of NCI with gender, age, educational level, depression, current CD4 count and lowest CD4 count. The association of NCI with depression remained in the Poisson regression (PR=1.96, 95%CI=1.12-3.42). The prevalence of cognitive impairment in HIV-positive patients estimated in this study is in accordance with international and Brazilian data. Of the factors analyzed, depression showed the greatest evidence of association with neurocognitive loss. Based on our findings, the inclusion of instruments to evaluate depression in our services for patients with HIV and acquired immunodeficiency syndrome (AIDS) is recommended.
- A novel effective method for the assessment of microvascular function in
male patients with coronary artery disease: a pilot study using laser
speckle contrast imaging
Abstract: Evaluation of microvascular endothelial function is essential for investigating the pathophysiology and treatment of cardiovascular and metabolic diseases. Although laser speckle contrast imaging technology is well accepted as a noninvasive methodology for assessing microvascular endothelial function, it has never been used to compare male patients with coronary artery disease with male age-matched healthy controls. Thus, the aim of this study was to determine whether laser speckle contrast imaging could be used to detect differences in the systemic microvascular functions of patients with established cardiovascular disease (n=61) and healthy age-matched subjects (n=24). Cutaneous blood flow was assessed in the skin of the forearm using laser speckle contrast imaging coupled with the transdermal iontophoretic delivery of acetylcholine and post-occlusive reactive hyperemia. The maximum increase in skin blood flow induced by acetylcholine was significantly reduced in the cardiovascular disease patients compared with the control subjects (74 vs 116%; P<0.01). With regard to post-occlusive reactive hyperemia-induced vasodilation, the patients also presented reduced responses compared to the controls (0.42±0.15 vs 0.50±0.13 APU/mmHg; P=0.04). In conclusion, laser speckle contrast imaging can identify endothelial and microvascular dysfunctions in male individuals with cardiovascular disease. Thus, this technology appears to be an efficient non-invasive technique for evaluating systemic microvascular and endothelial functions, which could be valuable as a peripheral marker of atherothrombotic diseases in men.
- Investigation of modified platelet-rich plasma (mPRP) in promoting the
proliferation and differentiation of dental pulp stem cells from deciduous
Abstract: Stem cells from human exfoliated deciduous teeth (SHEDs) have great potential to treat various dental-related diseases in regenerative medicine. They are usually maintained with 10% fetal bovine serum (FBS) in vitro. Modified platelet-rich plasma (mPRP) would be a safe alternative to 10% FBS during SHEDs culture. Therefore, our study aimed to compare the proliferation and differentiation of SHEDs cultured in mPRP and FBS medium to explore an optimal concentration of mPRP for SHEDs maintenance. Platelets were harvested by automatic blood cell analyzer and activated by repeated liquid nitrogen freezing and thawing. The platelet-related cytokines were examined and analyzed by ELISA. SHEDs were extracted and cultured with different concentrations of mPRP or 10% FBS medium. Alkaline phosphatase (ALP) activity was measured. Mineralization factors, RUNX2 and OCN, were measured by real-time PCR. SHEDs were characterized with mesenchymal stem cells (MSCs) markers including vimentin, CD44, and CD105. mPRP at different concentrations (2, 5, 10, and 20%) enhanced the growth of SHEDs. Moreover, mPRP significantly stimulated ALP activity and promoted expression of RUNX2 and OCN compared with 10% FBS. mPRP could efficiently facilitate proliferation and differentiation of SHEDs, and 2% mPRP would be an optimal substitute for 10% FBS during SHEDs expansion and differentiation in clinical scale manufacturing.
- Angiotensin-(1–7) inhibits inflammation and oxidative stress to relieve
lung injury induced by chronic intermittent hypoxia in rats
Abstract: Obstructive sleep apnea is associated with inflammation and oxidative stress in lung tissues and can lead to metabolic abnormalities. We investigated the effects of angiotensin1–7 [Ang-(1–7)] on lung injury in rats induced by chronic intermittent hypoxia (CIH). We randomly assigned 32 male Sprague-Dawley rats (180–200 g) to normoxia control (NC), CIH-untreated (uCIH), Ang-(1–7)-treated normoxia control (N-A), and Ang-(1–7)-treated CIH (CIH-A) groups. Oxidative stress biomarkers were measured in lung tissues, and expression of NADPH oxidase 4 (Nox4) and Nox subunits (p22phox, and p47phox) was determined by Western blot and reverse transcription-polymerase chain reaction. Pulmonary pathological changes were more evident in the uCIH group than in the other groups. Enzyme-linked immunosorbent assays and immunohistochemical staining showed that inflammatory factor concentrations in serum and lung tissues in the uCIH group were significantly higher than those in the NC and N-A groups. Expression of inflammatory factors was significantly higher in the CIH-A group than in the NC and N-A groups, but was lower than in the uCIH group (P<0.01). Oxidative stress was markedly higher in the uCIH group than in the NC and N-A groups. Expression of Nox4 and its subunits was also increased in the uCIH group. These changes were attenuated upon Ang-(1–7) treatment. In summary, treatment with Ang-(1-7) reversed signs of CIH-induced lung injury via inhibition of inflammation and oxidative stress.
- Loss to follow-up in anti-HCV-positive patients in a Brazilian regional
Abstract: Loss to follow-up (LF), which refers to patients who started care but voluntary stopped it, is a problem for patients with chronic disease. We aimed to estimate the rate of LF among patients seropositive for hepatitis C virus (HCV) and identify possible demographic and lifestyle risk factors associated with LF. From January 2009 through December 2012, 1010 anti-HCV-positive patients were included in the study. Among participants, 223 (22.1%) met the case definition for LF (more than 1-year elapsed since the last clinical appointment). Among 787 patients who remained in follow-up, 372 (47.2%) were discharged after undetectable HCV RNA, 88 (11.1%) were transferred (and remained on regular follow-up at the destination), and 25 (3.1%) died. According to univariate analysis, male gender, absence of a life partner, black race, psychiatric illness, previous alcohol abuse, previous or current recreational drug use, and previous or current smoking were significantly associated with LF. In multivariate analysis, absence of a life partner (adjusted odds ratio (AOR)=1.44; 95% confidence interval (95%CI)=1.03–2.02), black race (AOR=1.81, 95%CI=1.12–2.89), psychiatric illness (AOR=1.77, 95%CI=1.14–2.73), and the presence of at least one lifestyle risk factor (pertaining to substance abuse) (AOR=1.95, 95%CI=1.29–2.94) were independently associated with LF. Our study provides an estimate of the incidence of LF among anti-HCV-positive patients and identifies risk factors associated with this outcome. In addition, these results can help clinicians recognize patients at risk for LF, who require additional support for the continuity of care.
- Influence of storage time on DNA of Chlamydia trachomatis, Ureaplasma
urealyticum, and Neisseria gonorrhoeae for accurate detection by
quantitative real-time polymerase chain reaction
Abstract: The shipment and storage conditions of clinical samples pose a major challenge to the detection accuracy of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Ureaplasma urealyticum (UU) when using quantitative real-time polymerase chain reaction (qRT-PCR). The aim of the present study was to explore the influence of storage time at 4°C on the DNA of these pathogens and its effect on their detection by qRT-PCR. CT, NG, and UU positive genital swabs from 70 patients were collected, and DNA of all samples were extracted and divided into eight aliquots. One aliquot was immediately analyzed with qRT-PCR to assess the initial pathogen load, whereas the remaining samples were stored at 4°C and analyzed after 1, 2, 3, 7, 14, 21, and 28 days. No significant differences in CT, NG, and UU DNA loads were observed between baseline (day 0) and the subsequent time points (days 1, 2, 3, 7, 14, 21, and 28) in any of the 70 samples. Although a slight increase in DNA levels was observed at day 28 compared to day 0, paired sample t-test results revealed no significant differences between the mean DNA levels at different time points following storage at 4°C (all P>0.05). Overall, the CT, UU, and NG DNA loads from all genital swab samples were stable at 4°C over a 28-day period.
- Effect of different anesthetic agents on left ventricular systolic
function assessed by echocardiography in hamsters
Abstract: Determination of left ventricular ejection fraction (LVEF) using in vivo imaging is the cardiac functional parameter most frequently employed in preclinical research. However, there is considerable conflict regarding the effects of anesthetic agents on LVEF. This study aimed at assessing the effects of various anesthetic agents on LVEF in hamsters using transthoracic echocardiography. Twelve female hamsters were submitted to echocardiography imaging separated by 1-week intervals under the following conditions: 1) conscious animals, 2) animals anesthetized with isoflurane (inhaled ISO, 3 L/min), 3) animals anesthetized with thiopental (TP, 50 mg/kg, intraperitoneal), and 4) animals anesthetized with 100 mg/kg ketamine plus 10 mg/kg xylazine injected intramuscularly (K/X). LVEF obtained under the effect of anesthetics (ISO=62.2±3.1%, TP=66.2±2.7% and K/X=75.8±1.6%) was significantly lower than that obtained in conscious animals (87.5±1.7%, P<0.0001). The K/X combination elicited significantly higher LVEF values compared to ISO (P<0.001) and TP (P<0.05). K/X was associated with a lower dispersion of individual LVEF values compared to the other anesthetics. Under K/X, the left ventricular end diastolic diameter (LVdD) was increased (0.60±0.01 cm) compared to conscious animals (0.41±0.02 cm), ISO (0.51±0.02 cm), and TP (0.55±0.01 cm), P<0.0001. The heart rate observed with K/X was significantly lower than in the remaining conditions. These results indicate that the K/X combination may be the best anesthetic option for the in vivo assessment of cardiac systolic function in hamsters, being associated with a lower LVEF reduction compared to the other agents and showing values closer to those of conscious animals with a lower dispersion of results.
- Inactivated Pseudomonas aeruginosa inhibits hypoxia-induced pulmonary
hypertension by preventing TGF-β1/Smad signaling
Abstract: Pseudomonas aeruginosa is one of the common colonizing bacteria of the human body and is an opportunistic pathogen frequently associated with respiratory infections. Inactivated P. aeruginosa (IPA) have a variety of biological effects against inflammation and allergy. Transforming growth factor-β (TGF-β) signaling plays a critical role in the regulation of cell growth, differentiation, and development in a wide range of biological systems. The present study was designed to investigate the effects of IPA on TGF-β/Smad signaling in vivo, using a hypoxia-induced pulmonary hypertension (PH) rat model. Sprague Dawley rats (n=40) were exposed to 10% oxygen for 21 days to induce PH. At the same time, IPA was administered intravenously from day 1 to day 14. Mean pulmonary artery pressure (mPAP) and the right ventricle (RV) to left ventricle plus the interventricular septum (LV+S) mass ratio were used to evaluate the development of PH. Vessel thickness and density were measured using immunohistochemistry. Primary arterial smooth muscle cells (PASMCs) were isolated and the proliferation of PASMCs was assayed by flow cytometry. The production of TGF-β1 in cultured supernatant of PASMCs was assayed by ELISA. The expression levels of α-smooth muscle actin (α-SMA), TGF-β1 and phospho-Smad 2/3 in PASMCs were assayed by western blot. Our data indicated that IPA attenuated PH, RV hypertrophy and pulmonary vascular remodeling in rats, which was probably mediated by restraining the hypoxia-induced overactive TGF-β1/Smad signaling. In conclusion, IPA is a promising protective treatment in PH due to the inhibiting effects on TGF-β1/Smad 2/3 signaling.