Monocytes of patients with unstable angina express high levels of chemokine and pattern-recognition receptors.

BACKGROUND AND AIMS: Macrophages derived from monocytes play an important role in atherosclerosis progression. Subpopulations of circulating classical, intermediate, and non-classical monocytes possess distinct functions and phenotypes, and participate in the pathogenesis of disease. The aim of this study was to compare the quantity and phenotypes of circulating monocyte subpopulations in patients with established atherosclerosis and healthy control individuals. Additionally, the study aimed to provide insight into the functional activity of monocytes against a heat shock protein (HSP60). METHODS: Chemokine and pattern recognition receptors in monocyte subsets obtained from peripheral blood of acute and chronic coronary artery disease patients and controls were quantified by flow cytometry. Furthermore, monocytes from healthy controls were stimulated in vitro with HSP60, and the cytokines produced by them were evaluated by flow cytometry. RESULTS: Eighteen controls (C), 34 individuals with risk factors for cardiovascular disease (RF), 32 patients with stable angina (SA), and 16 patients with unstable angina (UA) were enrolled in the study. The absolute count of intermediate monocytes was found to be increased in patients of the UA group; high frequencies of the chemokine receptors CCR2, CCR5, and CX3CR1 were also observed in this subpopulation. Moreover, the pattern recognition receptors TLR2 and TLR4 were more frequent in intermediate monocytes from the UA group. Furthermore, the intermediate monocytes from healthy individuals produced IL-12p70 after stimulation with HSP60. CONCLUSIONS: Our results show that intermediate monocytes of UA patients exhibited an enhanced expression of the receptors involved in the recognition of damage-associated molecular patterns (DAMPs) and enhancement of the migratory function. Hence, they might contribute to the propagation and progression of inflammation observed in atherosclerosis, especially in the acute setting.

Frequency and characteristics of circulating CD4(+) CD28(null) T cells in patients with psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory disease that affects the skin. CD4(+) CD28(null) cells are a subset of T lymphocytes associated with systemic inflammation and increased cardiovascular disease risk, and may be involved in the pathogenesis of psoriasis. OBJECTIVES: To study the features of circulating CD4(+) CD28(null) cells in patients with psoriasis, adjusted for the influence of known cardiovascular disease risk factors. METHODS: Forty-two patients with psoriasis and 42 controls entered the study. Peripheral blood mononuclear cells were analysed for the frequency of CD4(+) CD28(null) T lymphocytes and their expression of cytotoxic granules and homing receptors. Immunostaining for cutaneous cytotoxic granules was assessed in skin biopsies from 11 patients. RESULTS: There were no differences in the frequency of CD4(+) CD28(null) T cells between groups in all situations analysed. However, there was an increased number of cells expressing cytotoxic granules and a decreased number expressing CXCR3 in ex vivo samples of patients with psoriasis. A negative correlation was observed between the frequency of ex vivo CD4(+) CD28(null) cells and psoriasis severity. After clinical remission in nine patients, ex vivo CD4(+) CD28(null) lymphocytes expressing cytotoxic granules decreased. Perforin-, granzyme B- and granulysin-containing cells were found in skin lesions. Patients with psoriasis also had increased plasma levels of C-reactive protein. CONCLUSIONS: These data suggest that cytotoxic cells, such as CD4(+) CD28(null) lymphocytes, within an inflammatory environment may play a role in the pathogenesis of psoriasis.

Persistent organic pollutants in liver of Brazilian sharpnose shark (Rhizoprionodon lalandii) from southeastern coast of Brazil.

In the present study, persistent organic pollutants (POPs) were determined in 14 livers from specimens of the Brazilian sharpnose shark (Rhizoprionodon lalandii), which is an important economic resource for small-scale fisheries on the southeastern coast of Brazil. The following concentrations (lipid weight) of POPs were found: ∑PCBs: 1019±267 ng g(-1); ∑DDTs: 111±40 ng g(-1) and ∑PBDEs: 10.4±4.78. PCB 153 made the greatest contribution to ∑PCB (21.4%), followed by PCB 138 (14.6%) and PCB 180 (9.94%). Among chlorinated pesticides, only the p,p'-DDE and p,p'-DDD isomers had concentrations above the detection limit. Moreover, levels above the detection limit were found only for PBDE congeners 47 and 100 (BDEs 47>99). On average, BDE 47 accounted for 88% of the total PBDE load. The feeding habits of the Brazilian sharpnose shark close to the Brazilian coastline are likely the most important difference regarding the accumulation of POPs in comparison to oceanic species that feed in deeper waters. Thus, this species may be used to evaluate the pollution of coastal areas as well as human exposure to contaminants, as the Brazilian sharpnose shark is a frequently used for human consumption. Further studies in other areas of Brazil and involving other species are needed to clarify the mechanisms and potential impact of POPs, which can affect the biology of different organisms and cause population declines.

Altered left ventricular diastolic function in subjects with spinal cord injury.

STUDY DESIGN: This is cross-sectional study. OBJECTIVES: The aim of this study is to investigate the cardiac structure and function of subjects with spinal cord injury (SCI) and the impact of metabolic, hemodynamic and inflammatory factors on these parameters. SETTING: São Paulo, Brazil. METHODS: Sixty-five nondiabetic, nonhypertensive, sedentary, nonsmoker men (34 with SCI and 31 healthy subjects) were evaluated by medical history, anthropometry, laboratory tests, analysis of hemodynamic and inflammatory parameters and echocardiography. RESULTS: Subjects with SCI had lower systolic blood pressure and higher levels of C-reactive protein and tumor necrosis factor receptors than the healthy ones. Echocardiography data showed that the SCI group presented similar left ventricular (LV) structural and systolic parameters, but lower initial diastolic velocity (Em) (9.2 ± 0.5 vs 12.3 ± 0.5 cm s(-1); P<0.001) and higher peak early inflow velocity (E)/Em ratio (7.7 ± 0.5 vs 6.1 ± 0.3; P = 0.009) compared with the able-bodied group, even after adjustment for systolic blood pressure and C-reactive protein levels. Furthermore, injured subjects with E/Em >8 had lower peak spectral longitudinal contraction (Sm) (9.0 ± 0.7 vs 11.6 ± 0.4 cm s(-1); P<0.001) and cardiac output (4.2 ± 0.2 vs 5.0 ± 0.2 l min(-1); P = 0.029), as well as higher relative wall thickness (0.38 ± 0.01 vs 0.35 ± 0.01; P = 0.005), than individuals with SCI with E/Em<8, but similar age, body mass index, blood pressure, injury level, metabolic parameters and inflammatory marker levels. CONCLUSION: Subjects with SCI presented impaired LV diastolic function in comparison with able-bodied ones. Moreover, worse LV diastolic function was associated with a pattern of LV concentric remodeling and subclinical decreases in systolic function among injured subjects. Overall, these findings might contribute to explain the increased cardiovascular risk reported for individuals with SCI.

Subclinical atherosclerosis is related to injury level but not to inflammatory parameters in spinal cord injury subjects.

STUDY DESIGN: Cross-sectional. OBJECTIVES: Individuals with spinal cord injury (SCI) exhibit increased carotid intima-media thickness (IMT) and are reported to be exposed to higher circulating levels of inflammatory mediators. This study evaluated the relationship between inflammatory markers and carotid surrogates of cardiovascular risk in subjects with SCI. SETTING: São Paulo, Brazil. METHODS: A total of 65 nondiabetic, nonhypertensive, sedentary, nonsmoker men (34 with SCI; 31 healthy subjects) were evaluated by medical history, anthropometry, routine laboratory tests, analysis of hemodynamic, inflammatory parameters and ultrasound examination of carotid arteries. RESULTS: Subjects with SCI (18 tetraplegic and 16 paraplegic) had lower systolic blood pressure (P = 0.009), higher serum C-reactive protein (P = 0.001), tumor necrosis factor (TNF) receptor-II (P = 0.02) and TNF receptor-I (P = 0.04) levels and increased in vitro production of interleukin-6 by mononuclear cells (P = 0.04), compared to able-bodied individuals. No differences in serum interleukin-6, e-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and transforming growth factor-ß levels, or in vitro release of interleukin-10, interleukin-17 and interferon-γ by mononuclear cells, were detected between the studied groups. Common carotid IMT, but not internal carotid resistive index, was significantly higher in subjects with SCI (P<0.0001 adjusted for C-reactive protein and TNF receptor-II levels). In addition, tetraplegic subjects exhibited increased IMT (P = 0.002 adjusted for systolic blood pressure and body mass index), but similar levels of inflammatory mediators compared to paraplegic ones. CONCLUSIONS: Individuals with SCI exhibit a clustering of vascular and inflammatory surrogates of increased cardiovascular risk. Nevertheless, subclinical carotid atherosclerosis is related to injury level but not to increased inflammatory status in these subjects.

Electrochemical therapy to treat cancer (in vivo treatment).

The aim of this paper is to present the evaluations and results attained by our research group from the clinical applications of Electrochemical Therapy (EChT in short) on tumors, specifically of cats and dogs. Our in vivo results indicate that EChT is an effective cancer treatment. Application of EChT in human beings was approved by National Health Surveillance Agency, which is linked to the Brazilian Ministry of Health. To make EChT available for cancer patients in the Brazil, basic studies were conducted and a Phase I clinical trial was started.

Artrogripose em caprino: relato de caso / Arthrogryposis in a goat: a case report

Relata-se a ocorrência de artrogripose congênita em um caprino fêmea da raça Anglo-Nubiana, no município de Viamão, RS, provavelmente induzida por hipertemia ocorrida durante a gestação.

Reproductive effects of endosulfan on male offspring of rats exposed during pregnancy and lactation.

1. The reproductive effects of endosulfan on the male offspring of rats were examined. Dams were treated orally with 0, 1.5 or 3.0 mg endosulfan/kg from day 15 of pregnancy to postnatal day (PND) 21 of lactation. The male offspring rats were investigated at PND 65 or 140, corresponding to the pubertal and adulthood stage of development. 2. The dose of 3.0 mg endosulfan/kg induced a decrease in maternal body weight during pregnancy, but litter size and mean birth weight were not affected. Similarly, the age at testis descent and preputial separation was not affected on the male offspring. 3. The daily sperm production (x10(6)) was permanently decreased in the highest dose group when investigated at puberty and at adulthood. At the lowest dose, however, the daily sperm production was significantly reduced only at puberty. 4. Histologically, the percentage of seminiferous tubules showing complete spermatogenesis was significantly decreased at puberty. This finding may explain the decrease in daily sperm production observed in the endosulfan-exposed male rats. 5. The results of this study show that low doses of endosulfan have no apparent effect on developmental landmarks or on the weight of reproductive and accessory sex organ. Daily sperm production was the most susceptible endpoint in the male offspring exposed to endosulfan during pregnancy and lactation. To further understand the reproductive effects of endosulfan on male rat offspring, additional reproductive and toxicokinetic studies should be carried out to determine the extent of endosulfan exposure in male rat offspring in utero and during lactation.

Preparation and preliminary X-ray diffraction studies of a new crystal form of L-asparaginase from Escherichia coli.

L-Asparaginase is an enzyme which hydrolyzes asparagine to produce aspartic acid and ammonia. It is an effective chemotherapeutic drug, especially in the treatment of acute lymphoblastic leukaemia in children. The enzyme from Escherichia coli was crystallized in a new crystal form with space group C2, unit-cell parameters a = 76.3 (0), b = 134.6 (2), c = 64.8 (7) A, beta = 110.5 (1) degrees and a dimer in the asymmetric unit. Synchrotron-radiation diffraction data have been collected to 1.95 A resolution.

Set-up and experimental parameters of the protein crystallography beamline at the Brazilian National Synchrotron Laboratory.

The Brazilian National Synchrotron Light Laboratory (LNLS) has a dedicated protein crystallography beamline. The optical elements of the beamline include an elastically bent cylindrical mirror and a triangular bent-crystal monochromator, which focus synchrotron radiation at the position of the sample in the vertical and horizontal planes, respectively. The monochromatic radiation is tunable between 2.0 and 1.2 A with the optimum wavelengths from 1.3 to 1.6 A, chosen to maximize the photon flux from the bending magnets of the storage ring (1.37 GeV). Diffraction images are recorded on a 345 mm-diameter MarResearch image-plate detector system with on-line readout. The experimental parameters of the beamline, such as the integral monochromatic flux and focus size, have been measured. The size of the beam at the position of the focal point is 0.5 x 0.5 mm(2). The flux density is between 4.4 x 10(10) and 8 x 10(10) photons s(-1) mm(-2) for wavelengths from 1.28 to 1.6 A. The energy resolution is sufficient to measure absorption edges of elements between 1.28 and 2 A. The facility, intended to serve the national and international community, has been commissioned and is available for users.