950 resultados para Laukkanen, Pauli (1): Rough road to dynamism


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The impact of peritoneal dialysis modality on patient survival and peritonitis rates is not fully understood, and no large-scale randomized clinical trial (RCT) is available. In the absence of a RCT, the use of an advanced matching procedure to reduce selection bias in large cohort studies may be the best approach. The aim of this study is to compare automated peritoneal dialysis (APD) and continuous ambulatory peritoneal dialysis (CAPD) according to peritonitis risk, technique failure and patient survival in a large nation-wide PD cohort. This is a prospective cohort study that included all incident PD patients with at least 90 days of PD recruited in the BRAZPD study. All patients who were treated exclusively with either APD or CAPD were matched for 15 different covariates using a propensity score calculated with the nearest neighbor method. Clinical outcomes analyzed were overall mortality, technique failure and time to first peritonitis. For all analysis we also adjusted the curves for the presence of competing risks with the Fine and Gray analysis. After the matching procedure, 2,890 patients were included in the analysis (1,445 in each group). Baseline characteristics were similar for all covariates including: age, diabetes, BMI, Center-experience, coronary artery disease, cancer, literacy, hypertension, race, previous HD, gender, pre-dialysis care, family income, peripheral artery disease and year of starting PD. Mortality rate was higher in CAPD patients (SHR1.44 CI95%1.21-1.71) compared to APD, but no difference was observed for technique failure (SHR0.83 CI95%0.69-1.02) nor for time till the first peritonitis episode (SHR0.96 CI95%0.93-1.11). In the first large PD cohort study with groups balanced for several covariates using propensity score matching, PD modality was not associated with differences in neither time to first peritonitis nor in technique failure. Nevertheless, patient survival was significantly better in APD patients.

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To compare the effect of acupuncture and occlusal splint in the treatment of temporomandibular disorders (TMD) in female patients.Method: Forty-eight female patients (mean age of 39.3±6.8 years) with diagnosed pain in muscles or joint according to RDC/TMD criteria were attended at UNESP - Aracatuba Dental School. Including criteria were reported pain in the chewing muscles and/or in the temporomandibular joint measured by a visual analogue scale (range from 0 to 10) and a reported reduction of the maximum mouth opening. Excluding factors were major occlusal problems, systemic diseases, pregnancy and age below 18 years. After randomization, the first group was treated with acupuncture performed by instructed dentist. The second group was treated with occlusal splint. The outcome variables were assessed at baseline (prior to the first treatment session) and after 1, 3 and 6 months. Primary criteria of success were improvement of mouth opening and pain reduction.Result: Acupuncture group exhibited chewing pain decrease from 5 (at baseline) to 1, 2 and 1 after 1, 3 and 6 months, respectively. In the splint group, chewing pain decreased from 4 to 2, 1 and 2 after 1, 3 and 6 months, respectively. The mouth opening (in mm) increased from 28 (at baseline) to 42, 44 and 46 after 1, 3 and 6 months, respectively in the acupuncture group. In the splint group, mouth opening improved from 29 to 40 after 1 month, and to 43 and 42 after 3 and 6 months. A significant pain reduction was noted for both groups when compared to the baseline (p<.001; Wilcoxon test). Acupuncture group had a significant clinical improvement of opening mouth (Mann-Whitney). Conclusion: The present outcomes suggest a positive association among acupuncture and occlusal splint on the reduction of chewing pain. Acupuncture was more effective in the mouth opening increase.

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On the basis of thin-section studies of cuttings and a core from two wells in the Amapa Formation of the Foz do Amazonas Basin, five main microfacies have been recognized within three stratigraphic sequences deposited during the Late Paleocene to Early Eocene. The facies are: 1) Ranikothalia grainstone to packstone facies; 2) ooidal grainstone to packstone facies; 3) larger foraminiferal and red algal grainstone to packstone facies; 4) Amphistegina and Helicostegina packstone facies; and 5) green algal and small benthic foraminiferal grainstone to packstone facies, divisible locally into a green algal and the miliolid foraminiferal subfacies and a green algal and small rotaliine foraminiferal subfacies. The lowermost sequence (Si) was deposited in the Late Paleocene-Early Eocene (biozone LF1, equivalent to P3-P6?) and includes rudaceous grainstones and packstones with large specimens of Ranikothalia bermudezi representative of the mid- and inner ramp. The intermediate and uppermost sequences (S2 and S3) display well-developed lowstand deposits formed at the end of the Late Paleocene (upper biozone LF1) and beginning of the Early Eocene (biozone LF2) on the inner ramp (larger foraminiferal and red algal grainstone to packstone facies), in lagoons (green algal and small benthic foraminiferal facies) and as shoals (ooidal facies) or banks (Amphistegina and Helicostegina facies). Depth and oceanic influence were the main controls on the distribution of these microfacies. Stratal stacking patterns evident within these sequences may well have been related to sea level changes postulated for the Late Paleocene and Early Eocene. During this time, the Amapa Formation was dominated by cyclic sedimentation on a gently sloping ramp. Environmental and ecological stress brought about by sea level change at the end of the biozone LF1 led to the extinction of the larger foraminifera (Ranikothalia bermudezi). (c) 2009 Elsevier B.V. All rights reserved.

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Objective: NALP3-inflammasome is an innate mechanism, alternative to type-1 interferon, which is able to recognize nucleic acids and viruses in the cytoplasm and to induce pro-inflammatory response. Here, we hypothesized the involvement of inflammasome in the early defense against HIV-1 and in the full maturation of dendritic cells: for this, we evaluated the response of dendritic cells pulsed with HIV-1 in terms of inflammasome activation in healthy donors. Moreover, inflammasome response to HIV was evaluated in HIV-infected individuals. Design and methods: Monocyte-derived dendritic cells isolated from 20 healthy individuals (HC-DC) and 20 HIV-1-infected patients (HIV-DC) were pulsed with alditrithiol-2-inactivated HIV-1. We then analyzed inflammasome genes expression and interleukin-1 beta (IL-1 beta) secretion. Results: In HC-DC, HIV-1 induced higher NLRP3/NALP3 mRNA expression compared with other inflammasome genes such as NALP1/NLRP1 or IPAF/NLRC4 (P < 0.001). This augmented expression was accompanied by CASP1-increased and IL1B-increased mRNA levels and by a significant increment of IL-1b secretion (P < 0.05). Otherwise, HIV-1 failed to activate inflammasome and cytokine production in HIV-DC. HIV-DC showed an increased NLRP3/NALP3 basal expression, suggesting a chronic inflammatory profile of patients' immune cells. Conclusion: HIV-1 was able to induce a NALP3-inflammasome response in healthy individuals, indicating that this inflammasome could play a role in the first steps of HIV-1 infection; the consequent inflammatory process may be important for directing host immune response against the virus and/or disease progression. HIV-DC seemed to be chronically activated, but unresponsive against pathogens. Our findings could be of interest considering the ongoing research about dendritic cell manipulation and therapeutic strategies for AIDS involving dendritic cell-based immune-vaccines. (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

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Aflatoxin M-1 (AFM(1)) is a hepatocarcinogen found in milk of animals that have consumed feeds with aflatoxin B-1. The carry-over of AFM(1) from milk to Minas Frescal cheese produced with or without starter cultures was determined. 40 L of milk were divided into 10 L each and assigned to the following treatments for cheese manufacture: 0.250 rig AFM(1) mL(-1), 0.500 rig AFM(1) mL(-1), 0.250 ng AFM(1) mL(-1) + starter, 0.500 ng AFM(1) mL(-1) + starter. Quantification of AFM(1) was achieved by high performance liquid chromatography. The carry-over of AFM(1) from milk to cheese ranged from 30.64% to 42.26%. There was no effect of storage time on AFM(1). Milk with AFM(1) in levels studied may concentrate the toxin in Minas Frescal cheese, but at concentrations below the Brazilian tolerance limit. The addition of starter cultures did not influence concentration or stability of the AFM(1) in cheese over 30 days storage. (C) 2011 Elsevier Ltd. All rights reserved.

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Aim This randomized, controlled, clinical study compared two surgical techniques for root coverage with the acellular dermal matrix graft (ADMG) to evaluate which procedure could provide better root coverage and greater amounts of keratinized tissue. Materials and Methods Fifteen pairs of bilateral Miller Class I or II gingival recessions were treated and assigned randomly to the test group, and the contra-lateral recessions were assigned to the control group. The ADMG was used in both groups. In the control group, the graft and flap were positioned at the level of the cemento-enamel junction (CEJ), and in the test group, the graft was positioned 1 mm apical to the CEJ and the flap 1 mm coronal to the CEJ. The clinical parameters were taken before the surgeries and after 6 months. The gingival recession area, a new parameter, was measured in standardized photographs through a special device and software. Results There were statistically significant differences favouring the proposed technique for all parameters except for the amount of keratinized tissue at 6 months. Conclusions The proposed test technique is more suitable for root coverage procedures with ADMG, and the new parameter evaluated appears valuable for root coverage analysis. (Clinicaltrials.gov Identifier: NCT01175720).

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Background: Kinins participate in the pathophysiology of obesity and type 2 diabetes by mechanisms which are not fully understood. Kinin B-1 receptor knockout mice (B-1(-/-)) are leaner and exhibit improved insulin sensitivity. Methodology/Principal Findings: Here we show that kinin B-1 receptors in adipocytes play a role in controlling whole body insulin action and glucose homeostasis. Adipocytes isolated from mouse white adipose tissue (WAT) constitutively express kinin B-1 receptors. In these cells, treatment with the B-1 receptor agonist des-Arg(9)-bradykinin improved insulin signaling, GLUT4 translocation, and glucose uptake. Adipocytes from B-1(-/-) mice showed reduced GLUT4 expression and impaired glucose uptake at both basal and insulin-stimulated states. To investigate the consequences of these phenomena to whole body metabolism, we generated mice where the expression of the kinin B-1 receptor was limited to cells of the adipose tissue (aP2-B-1/B-1(-/-)). Similarly to B-1(-/-) mice, aP2-B-1/B-1(-/-) mice were leaner than wild type controls. However, exclusive expression of the kinin B1 receptor in adipose tissue completely rescued the improved systemic insulin sensitivity phenotype of B-1(-/-) mice. Adipose tissue gene expression analysis also revealed that genes involved in insulin signaling were significantly affected by the presence of the kinin B-1 receptor in adipose tissue. In agreement, GLUT4 expression and glucose uptake were increased in fat tissue of aP2-B-1/B-1(-/-) when compared to B-1(-/-) mice. When subjected to high fat diet, aP2-B-1/B-1(-/-) mice gained more weight than B-1(-/-) littermates, becoming as obese as the wild types. Conclusions/Significance: Thus, kinin B-1 receptor participates in the modulation of insulin action in adipocytes, contributing to systemic insulin sensitivity and predisposition to obesity.

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The diffusive gradients in thin films (DGT) technique has shown enormous potential for labile metal monitoring in fresh water due to the preconcentration, time-integrated, matrix interference removal and speciation analytical features. In this work, the coupling of energy dispersive X-ray fluorescence (EDXRF) with paper-based DGT devices was evaluated for the direct determination of Mn, Co. Ni, Cu, Zn and Pb in fresh water. The DGT samplers were assembled with cellulose (Whatman 3 MM chromatography paper) as the diffusion layer and a cellulose phosphate ion exchange membrane (Whatman P 81 paper) as the binding agent. The diffusion coefficients of the analytes on 3 MM chromatography paper were calculated by deploying the DGT samplers in synthetic solutions containing 500 mu g L-1 of Mn. Co, Ni, Cu, Zn and Pb (4 L at pH 5.5 and ionic strength at 0.05 mol L-1). After retrieval, the DGT units were disassembled and the P81 papers were dried and analysed by EDXRF directly. The 3 MM chromatographic paper diffusion coefficients of the analytes ranged from 1.67 to 1.87 x 10(-6) cm(2) s(-1). The metal retention and phosphate group homogeneities on the P81 membrane was studied by a spot analysis with a diameter of 1 mm. The proposed approach (DGT-EDXRF coupling) was applied to determine the analytes at five sampling sites (48 h in situ deployment) on the Piracicaba river basin, and the results (labile fraction) were compared with 0.45 mu m dissolved fractions determined by synchrotron radiation-excited total reflection X-ray fluorescence (SR-TXRF). The limits of detection of DGT-EDXRF coupling for the analytes (from 7.5 to 26 mu g L-1) were similar to those obtained by the sensitive SR-TXRF technique (3.8 to 9.1 mu g L-1). (C) 2012 Elsevier B.V. All rights reserved.

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A study was designed to characterize a carbapenem-resistant Klebsiella pneumoniae (KPSA01) isolated from a patient in Gauteng, South Africa without recent travel outside South Africa. Molecular characterization was done using isoelectric focusing, polymerase chain reaction and sequencing for bla(VIM), bla(IMP), bla(NDM), bla(CTX-Ms), bla(OXAs), bla(TEMs), and bla(SHV), plasmid-mediated quinolone resistance determinants, multilocus sequencing typing, plasmid replicon typing, and addiction factors. KPSA01 produced VIM-1 and belonged to the newly described sequence type ST569. The plasmid that harboured bla(VIM) typed within the narrow host range IncF replicon group, contained the aadA1 gene cassette, and tested positive for the vagCD and ccdAB addiction systems. This is the first report of VIM-1-producing K. pneumoniae outside Europe. It is important that surveillance studies be undertaken in Africa to determine if VIM-1-producing K. pneumoniae are present in significant numbers.

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The midbrain dorsal periaqueductal gray (dPAG) has an important role in orchestrating anxiety-and panic-related responses. Given the cellular and behavioral evidence suggesting opposite functions for cannabinoid type 1 receptor (CB1) and transient receptor potential vanilloid type-1 channel (TRPV1), we hypothesized that they could differentially influence panic-like reactions induced by electrical stimulation of the dPAG. Drugs were injected locally and the expression of CB1 and TRPV1 in this structure was assessed by immunofluorescence and confocal microscopy. The CB1-selective agonist, ACEA (0.01, 0.05 and 0.5 pmol) increased the threshold for the induction of panic-like responses solely at the intermediary dose, an effect prevented by the CB1-selective antagonist, AM251 (75 pmol). Panicolytic-like effects of ACEA at the higher dose were unmasked by pre-treatment with the TRPV1 antagonist capsazepine (0.1 nmol). Similarly to ACEA, capsazepine (1 and 10 nmol) raised the threshold for triggering panic-like reactions, an effect mimicked by another TRPV1 antagonist, SB366791 (1 nmol). Remarkably, the effects of both capsazepine and SB366791 were prevented by AM251 (75 pmol). These pharmacological data suggest that a common endogenous agonist may have opposite functions at a given synapse. Supporting this view, we observed that several neurons in the dPAG co-expressed CB1 and TRPV1. Thus, the present work provides evidence that an endogenous substance, possibly anandamide, may exert both panicolytic and panicogenic effects via its actions at CB1 receptors and TRPV1 channels, respectively. This tripartite set-point system might be exploited for the pharmacotherapy of panic attacks and anxiety-related disorders. Neuropsychopharmacology (2012) 37, 478-486; doi:10.1038/npp.2011.207; published online 21 September 2011

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Objective Several implant surfaces are being developed, some in the nanoscale level. In this study, two different surfaces had their early healing properties compared in context of circumferential defects of various widths. Material and methods Six dogs had the mandibular premolars extracted. After 8weeks, four implants were placed equicrestally in each side. One acted as control, while the others were inserted into sites with circumferential defects of 1.0, 1.5 and 2.0mm wide and 5mm deep. A nano-modified surface was used on one side and a micro-rough on the other. Bone markers were administered on the third day after implant placement and then after 1, 2, 4weeks to investigate the bone formation dynamic through fluorescence analysis. Ground sections were prepared from 8-week healing biopsies and histomorphometry was performed. Results The fluorescence evaluation of the early healing showed numerically better results for the nano-modified group; however this trend was not followed by the histomorphometric evaluation. A non-significant numerical superiority of the micro-rough group was observed in terms of vertical bone apposition, defect bone fill, bone-to-implant contact and bone density. In the intra-group analysis, the wider defects showed the worse results while the control sites showed the best results for the different parameters, but without statistical relevance. Conclusion Both surfaces may lead to complete fill of circumferential defects, but the gap width has to be considered as a challenge. The nano-scale modification was beneficial in the early stages of bone healing, but the micro-rough surface showed numerical better outcomes at the 8-week final period.

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B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) is a Polycomb group protein that is able to induce telomerase activity, enabling the immortalization of epithelial cells. Immortalized cells are more susceptible to double-strand breaks (DSB), which are subsequently repaired by homologous recombination (HR). BRCA1 is among the HR regulatory genes involved in the response to DNA damage associated with the RAD51 protein, which accumulates in DNA damage foci after signaling H2AX, another important marker of DNA damage. Topoisomerase III beta (topoIII beta) removes HR intermediates before chromosomal segregation, preventing damage to cellular DNA structure. In breast carcinomas positive for BMI-1 the role of proteins involved in HR remains to be investigated. The aim of this study was to evaluate the association between BMI-1 and homologous recombination proteins. Using tissue microarrays containing 239 cases of primary breast tumors, the expression of Bmi-1, BRCA-1, H2AX, Rad51, p53, Ki-67, topoIII beta, estrogen receptors (ER), progesterone receptors (PR), and HER-2 was analyzed by immunohistochemistry. We observed high Bmi-1 expression in 66 cases (27.6%). Immunohistochemical overexpression of BMI-1 was related to ER (p=0.004), PR (p<0.001), Ki-67 (p<0.001), p53 (p=0.003), BRCA1 (p=0.003), H2AX (p=0.024) and topoIII beta (p<0,001). Our results show a relationship between the expression of BMI-1 and HR regulatory genes, suggesting that Bmi-1 overexpression might be an important event in HR regulation. However, further studies are necessary to understand the mechanisms in which Bmi-1 could regulate HR pathways in invasive ductal breast carcinomas.

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The objective of this study was to observe possible interactions between the renin-angiotensin and nitrergic systems in chronic hypoxia-induced pulmonary hypertension in newborn piglets. Thirteen chronically instrumented newborn piglets (6.3 +/- 0.9 days; 2369 +/- 491 g) were randomly assigned to receive saline (placebo, P) or the AT(1) receptor (AT(1)-R) blocker L-158,809 (L) during 6 days of hypoxia (FiO(2) = 0.12). During hypoxia, pulmonary arterial pressure (Ppa; P < 0.0001), pulmonary vascular resistance (PVR; P < 0.02) and the pulmonary to systemic vascular resistance ratio (PVR/SVR; P < 0.05) were significantly attenuated in the L (N = 7) group compared to the P group (N = 6). Western blot analysis of lung proteins showed a significant decrease of endothelial NOS (eNOS) in both P and L animals, and of AT(1)-R in P animals during hypoxia compared to normoxic animals (C group, N = 5; P < 0.01 for all groups). AT(1)-R tended to decrease in L animals. Inducible NOS (iNOS) did not differ among P, L, and C animals and iNOS immunohistochemical staining in macrophages was significantly more intense in L than in P animals (P < 0.01). The vascular endothelium showed moderate or strong eNOS and AT(1)-R staining. Macrophages and pneumocytes showed moderate or strong iNOS and AT(1)-R staining, but C animals showed weak iNOS and AT(1)-R staining. Macrophages of L and P animals showed moderate and weak AT(2)-R staining, respectively, but the endothelium of all groups only showed weak staining. In conclusion, pulmonary hypertension induced by chronic hypoxia in newborn piglets is partially attenuated by AT(1)-R blockade. We suggest that AT(1)-R blockade might act through AT(2)-R and/or Mas receptors and the nitrergic system in the lungs of hypoxemic newborn piglets.

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Knowledge of hospital costs is highly important for public health decision-making. This study aimed to estimate direct hospital costs related to pneumococcal meningitis in children 13 years or younger in the city of Sao Jose dos Campos, Sao Paulo State, Brazil, from January 1999 to December 2008. Data were obtained from medical records. Hospital costs were calculated according to the mixed method for measurement of quantities of items with identified costs and value attribution to items consumed (micro-costing and gross-costing). All costs were calculated according to monetary values for November 2009 and in Brazilian currency (Real). Epi Info 3.5.1 was used for frequencies and means analysis. Forty-one cases were reported. Direct hospital costs varied from R$ 1,277.90 to R$ 19,887.56 (mean = R$ 5,666.43), or 10 to 20 times the mean cost of hospitalization for other diseases. Hospital staff labor was the highest cost, followed by medication, procedures, supplies, and lab tests.

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Objective. Monocyte chemotactic protein (MCP-1), involved in the pathogenesis of lupus nephritis (LN), has recently been indicated as a new biomarker of kidney activity in systemic lupus erythematosus (SLE). Our aim was to assess urinary MCP-1 (uMCP-1) as a biomarker of renal activity in patients with SLE and to compare it to other disease activity markers, using the ELISA. Methods. Seventy-five female Brazilian patients with SLE and a control group participated in our study. Patients with SLE were distributed among 3 groups according to kidney involvement and classified according to disease activity based on clinical and laboratory measures such as urinary sediment, proteinuria, kidney function, C3, C4, anti-dsDNA, disease activity index, and renal SLE disease activity index. The serum and uMCP-1 concentrations were measured by sandwich ELISA. Results. In the A-LN group (active lupus nephritis: SLE with kidney involvement), the concentration of uMCP-1 was significantly higher than in other groups. A cutoff point was established using the results of the control group to apply this test in the detection of LN. A-LN had a higher frequency of positive results for uMCP-1 in comparison to the other groups (p < 0.001). To detect disease activity in patients with LN, a new cutoff was determined based on the results of patients with SLE with kidney involvement. Setting specificity at 90%, the sensitivity of the test was 50%. Conclusion. The high specificity makes uMCP-1 a useful test as a predictor of kidney activity in SLE, especially when associated to other measures used in clinical practice. (First Release Sept 1 2012; J Rheumatol 2012;39:1948-54; doi :10.3899/jrheum.110201)