Proteinase-activated receptors, targets for kallikrein signaling

Serine proteinases like thrombin can signal to cells by the cleavage/activation of proteinase-activated receptors (PARs). Although thrombin is a recognized physiological activator of PAR(1) and PAR(4), the endogenous enzymes responsible for activating PAR(2) in settings other than the gastrointestinal system, where trypsin can activate PAR(2), are unknown. We tested the hypothesis that the human tissue kallikrein (hK) family of proteinases regulates PAR signaling by using the following: 1) a high pressure liquid chromatography (HPLC)-mass spectral analysis of the cleavage products yielded upon incubation of hK5, -6, and -14 with synthetic PAR N-terminal peptide sequences representing the cleavage/activation motifs of PAR(1), PAR(2), and PAR(4); 2) PAR-dependent calcium signaling responses in cells expressing PAR(1), PAR(2), and PAR(4) and in human platelets; 3) a vascular ring vasorelaxation assay; and 4) a PAR(4)-dependent rat and human platelet aggregation assay. We found that hK5, -6, and -14 all yielded PAR peptide cleavage sequences consistent with either receptor activation or inactivation/disarming. Furthermore, hK14 was able to activate PAR(1), PAR(2), and PAR(4) and to disarm/inhibit PAR(1). Although hK5 and -6 were also able to activate PAR(2), they failed to cause PAR(4)-dependent aggregation of rat and human platelets, although hK14 did. Furthermore, the relative potencies and maximum effects of hK14 and -6 to activate PAR(2)-mediated calcium signaling differed. Our data indicate that in physiological settings, hKs may represent important endogenous regulators of the PARs and that different hKs can have differential actions on PAR(1), PAR(2), and PAR(4).

Chronic supplementation of beta-hydroxy-beta methylbutyrate (HM beta) increases the activity of the GH/IGF-I axis and induces hyperinsulinemia in rats

Objective: Beta-hydroxy-beta-methylbutyrate (HM beta) is a metabolite of leucine widely used for improving sports performance. Although limp is recognized to promote anabolic or anti-catabolic effects on protein metabolism, the impact of its long-term use on skeletal muscle and/or genes that control the skeletal protein balance is not fully known. This study aimed to investigate whether chronic HM beta treatment affects the activity of GH/IGF-I axis and skeletal muscle IGF-I and myostatin mRNA expression. Design: Rats were treated with HK beta (320 mg/kg BW) or vehicle, by gavage, for 4 weeks, and killed by decapitation. Blood was collected for evaluation of serum insulin, glucose and IGF-I concentrations. Samples of pituitary, liver, extensor digitorum longus (EDL) and soleus muscles were collected for total RNA or protein extraction to evaluate the expression of pituitary growth hormone (GH) gene (mRNA and protein), hepatic insulin-like growth factor I (IGF-I) mRNA, skeletal muscle IGF-I and myostatin mRNA by Northern blotting/real time-PCR, or Western blotting. Results: Chronic HM beta treatment increased the content of pituitary GH mRNA and GH, hepatic IGF-I mRNA and serum IGF-I concentration. No changes were detected on skeletal muscle IGF-I and myostatin mRNA expression. However, the HIM-treated rats although normoglycemic, exhibited hyperinsulinemia. Conclusions: The data presented herein extend the body of evidence on the potential role of HM beta-treatment in stimulating GH/IGF-I axis activity. In spite of this effect, HM beta supplementation also induces an apparent insulin resistance state which might limit the beneficial aspects of the former results, at least in rats under normal nutritional status and health conditions. (C) 2010 Growth Hormone Research Society. Published by Elsevier Ltd. All rights reserved.

Utvärdering av Elektronisk fakturahantering inom Banverket

Vår uppdragsgivare Banverket efterfrågade en utvärdering av elektronisk fakturahantering(EFH) vid Banverket som infördes för cirka två år sedan. Det finns några olika verktyg för EFH, skanning av pappersfakturor är ett av de verktygen som Banverket använder för att hantera pappersfakturor från olika leverantörer. Vårt mål med uppsatsen var att analysera vilken effekt användningen av EFH får för Banverket.I vår analys studerades effekter av det införda systemet för elektronisk fakturahantering. Uppsatsen har gjorts med hjälp av en kvalitativ undersöknings metod, analysmetoden FA/SIM samt litteraturstudier inom ämnet. Vi har intervjuat personal vid Banverket Produktion och Banregioner i Malmö samt Stockholm. Vi har även intervjuat personal vid HK, Projektering och Telenät i Borlänge.Efter vår analys har vi kommit fram till att det finns stora ekonomiska vinster med elektronisk fakturahantering, men även vinster som inte är direkt mätbara. De viktigaste effekterna är att inga fakturor kommer bort efter de har skannats in och systemet har hela tiden reda på var i flödet fakturan befinner sig, det vill säga bättre kontroll har vunnits. Genom införandet av EFH har flera arbetsmoment försvunnit eller automatiserats och hanteringen av fakturor har förenklats, vilket bidrar till mindre kostnader för hantering av fakturor. Med EFH behöver användarna inte ta kopior av fakturor eftersom de hela tiden finns i systemet. När det gäller minskad dröjsmålsränta har vi kommit fram till att Banverket bör ha minskat kostnaderna för dröjsmålsränta.

Push or pull? : The relationship between quality of care and use of complementary and alternative medicine among patients with lung cancer in Sweden

Little is known about relationships between quality of care (QoC) and use of complementary and alternative medicine (CAM) among patients with lung cancer (LC). Purpose: This study examines CAM-use among patients with LC in Sweden, associations between QoC and CAM-use among these patients, and reported aspects of LC-care perceived as particularly positive and negative by patients, as well as suggestions for improving QoC. Methods: Survey data from 94 patient members of the Swedish LC patient organization about CAM-use and QoC as measured by the instrument “Quality from the patient’s perspective” were analyzed. Results: Fifty (53%) LC-patients used CAM, with 40 of the CAM-users reporting that CAM helped them. The most common CAMs used were dietary supplements and natural remedies, followed by prayer. Significantly more patients reported using prayer and meditation for cure than was the case for other types of CAM used. Less than half the CAM-users reported having spoken with staff from the biomedical health care system about their CAM-use. Patients provided numerous suggestions for improving LC-care in a variety of areas, aiming at a more effective and cohesive care trajectory. No differences in QoC were found between CAM-users and non-CAM-users, but differences in CAM-use i.e. type of CAM, reasons for using CAM, and CAM-provider consulted could be associated with different experiences of care. Conclusions: It is important to recognize that CAM-users are not a homogeneous group but might seek different types of CAMs and CAM-providers in different situations depending on experiences of care.

Mutagenicity and antimutagenicity of (-)-hinokinin a trypanosomicidal compound measured by Salmonella microsome and comet assays

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Estimativa de espessura crustal na Província Borborema (NE/Brasil) através de função do recpetor

Crustal thickness and VP/VS estimates are essential to the studies of subsurface geological structures and also to the understanding of the regional tectonic evolution of a given area. In this dissertation, we use the Langston´s (1979) Receiver Function Method using teleseismic events reaching the seismographic station with angles close to the vertical. In this method, the information of the geologic structures close to the station is isolated so that effects related to the instrument response and source mechanics are not present. The resulting time series obtained after the deconvolution between horizontal components contains the larger amplitude referring to the P arrival, followed by smaller arrival caused by the reverberation and conversion of the P-wave at the base of the crust. We also used the HK-Stacking after Zhu & Kanamori (2000) to obtain crustal thickness and Vp/VS estimates. This method works stacking receiver functions so that the best estimates of crustal thickness and Vp/VS are found when the direct P, the Ps wave and the first multiple are coherently stacked. We used five broadband seismographic stations distributed over the Borborema Province, NE Brazil. Crustal thickness and Vp/VS estimates are consistent with the crust-mantle interface obtained using gravity data. We also identified crutal thickening in the NW portion of the province, close to Sobral/CE. Towards the center-north portion of the province, there is an evident crustal thinning which coincides with a geological feature consisting of an alignment of sedimentary basins known as the Cariris-Potiguar trend. Towards the NE portion of the province, in Solânea/PB and Agrestina/PE regions, occurs a crustal thickening and a systematic increase in the VP/VS values which suggest the presence of mafic rocks in the lower crust also consistent with the hypothesis of underplating in the region

Occurrence of sibling species of Lutzomyia longipalpis (Diptera : Psychodidae) in Venezuela: First evidence from reproductively isolated sympatric populations

The delimitation of cryptic species within the main vector of the American visceral leishmaniasis, Lutzomyia longipalpis, remains a topic of controversy. An analysis of generic variability based on 8 enzymatic loci revealed fixed differences in 2 diagnostic loci, adenylate kinase (Ak) and hexokinase (Hk), between sympatric and allopatric populations at 4 localities in Venezuela. The absence of heterozygotes for these 2 loci within 1 locality indicates, for the first time, the presence of 2 sympatric reproductively isolated populations or cryptic species within L. longipalpis. Significant differences were also detected between these cryptic species in the allele frequencies of glucose-6-phosphate isomerase (Gpi) and malate dehydrogenase, decarboxylating (Me). One species showed mean heterozygosities that ranged between 6.6% and 6.7%, with 1.6-1.9 alleles detected per locus, while the other had mean heterozygosities that ranged from 4.3% to 6.3%, with 1.3-1.6 alleles per locus. Comparisons of isozyme profiles with published data suggests that 1 species is similar to the L. longipalpis described in Colombian and Brazilian populations, whereas the other has not been previously reported.

On the hardy space H¹ on products of half-spaces

We show that the Hardy space H¹ anal (R2+ x R2+) can be identified with the class of functions f such that f and all its double and partial Hubert transforms Hk f belong to L¹ (R2). A basic tool used in the proof is the bisubharmonicity of |F|q, where F is a vector field that satisfies a generalized conjugate system of Cauchy-Riemann type.

Effect of the dibenzylbutyrolactone lignan (-)-hinokinin on doxorubicin and methyl methanesulfonate clastogenicity in V79 Chinese hamster lung fibroblasts

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Toxicity of hypercaloric diet and monosodium glutamate: oxidative stress and metabolic shifting in hepatic tissue.

The present study examines the effects of a hypercaloric diet on hepatic glucose metabolism of young rats, with and without monosodium glutamate (MSG) administration, and the association of these treatments with evaluating markers of oxidative stress. Male weaned Wistar rats (21 days old) from mothers fed with a hypercaloric diet or a normal diet, were divided into four groups (n=6): control (C) fed with control diet; (MSG) treated with MSG (4 mg/g) and control diet; (HD) fed with hypercaloric diet and (MSG-HD) treated with MSG and HD. Rats were sacrificed after the oral glucose tolerance test (OGTT), at 45 days of treatments. Serum was used for insulin determination. Glycogen, hexokinase(HK), glucose-6-phosphatase(G6PH), lipid hydroperoxide, superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px) were determined in liver. HD rats showed hypoglycemia, hyperinsulinemia, and high hepatic glycogen, HK and decreased G6PH. MSG and MSG-HD had hyperinsulinemia, hyperglycemia, decreased HK and increased G6PH in hepatic tissue. These animals had impaired OGTT. HD, MSG and MSG-HD groups had increased lipid hydroperoxide and decreased SOD in hepatic tissue. Hypercaloric diet and monosodium glutamate administration induced alterations in metabolic rate of glucose utilization and decreased antioxidant defenses. Therefore, the hepatic glucose metabolic shifting induced by HD intake and MSG administration were associated with oxidative stress in hepatic tissue.

Ajuste metabólico e respostas imunes de pacus juvenis alimentados com diferentes níveis de carboidratos e submetidos a jejum prolongado

Pós-graduação em Zootecnia - FCAV

Desgaste e rugosidade superficial de um cimento de ionômero de vidro nanoparticulado

To compare the abrasion wear resistance and superficial roughness of different glass ionomer cements used as restorative materials, focusing on a new nanoparticulate material. Material and Method: Three glass ionomer cements were evaluated: Ketac Molar, Ketac N100 and Vitremer (3M ESPE, St. Paul, MN, USA), as well as the Filtek Z350 (3M ESPE, St. Paul, MN, USA). For each material were fabricated circular specimens (n=12), respecting the handling mode specified by the manufacturer, which were polished with sandpaper disks of decreasing grit. The wear was determined by the amount of mass (M) lost after brushing (10,000 cycles) and the roughness (Ra) using a surface roughness tester. The difference between the Minitial and Mfinal (ΔM) as well as beroughness of aesthetic restorative materials: an in vitro comparison. SADJ. 2001; 56(7): 316-20. 11. Yip HK, Peng D, Smales RJ. Effects of APF gel on the physical structure of compomers and glass ionomer cements. Oper. Dent. 2001; 26(3): 231-8. 12. Ma T, Johnson GH, Gordon GE. Effects of chemical disinfectants on the surface characteristics and color of denture resins. J Prosthet Dent 1997; 77(2): 197-204. 13. International organization for standardization. Technical specification 14569-1. Dental Materials – guidance on testing of wear resistance – PART I: wear by tooth brushing. Switzerland: ISO; 1999. 14. Bollen CML, Lambrechts P, Quirynen M. Comparison of surface roughness of oral hard materials to the threshold surface roughness for bacterial plaque retention: a review of the literature. Dent Mater.1997; 13(4): 258-9. 15. Kielbassa AM, Gillmann C, Zantner H, Meyer-Lueckel H, Hellwig E, Schulte-Mönting J. Profilometric and microradiographic studies on the effects of toothpaste and acidic gel abrasivity on sound and demineralized bovine dental enamel. Caries Res. 2005; 39(5): 380-6. 16. Tanoue N, Matsumara H, Atsuta M. Wear and surface roughness of current prosthetic composites after toothbrush/dentifrice abrasion. J Prosthet Dent. 2000; 84(1): 93-7. 17. Heath JR, Wilson HJ. Abrasion of restorative materials by toothpaste. J Oral Rehabil. 1976; 3(2): 121-38. 18. Frazier KB, Rueggeberg FA, Mettenburg DJ. Comparasion of wearresistance of class V restorative materials. J Esthet Dent. 1998; 10(6): 309-14. 19. Momoi Y, Hirosakil K, Kohmol A, McCabe JF. In vitro toothebrushdentifrrice abrasion of resin-modified glass ionomers. Dent Mater. 1997; 13(2): 82-8. 20. Turssi CP, Magalhães CS, Serra MC, Rodrigues Jr.AL. Surface roughness assessment of resin-based materials during brushing preceded by pHcycling simulations. Oper Dent. 2001; 26(6): 576-84. 21. Wang L, Cefaly DF, Dos Santos JL, Dos Santos JR, Lauris JR, Mondelli RF, et al. In vitro interactions between lactic acid solution and art glassionomer cements. J Appl Oral Sci. 2009; 17(4): 274-9. 22. Carvalho FG, Fucio SB, Paula AB, Correr GM, Sinhoreti MA, PuppinRontani RM. Child toothbrush abrasion effect on ionomeric materials. J Dent Child (Chic). 2008; 75(2): 112-6. 23. Coutinho E, Cardoso MV, De Munck J, Neves AA, Van Landuyt KL, Poitevin A, et al. Bonding effectiveness and interfacial characterization of a nano-filled resin-modified glass-ionomer. Dent Mater. 2009; 25(11): 1347-57. tween Rainitial and Rafinal (ΔRa) were also used for statistical analysis (α=0.05). Results: Except for the composite, significant loss of mass was observed for all glass ionomer cements and the ΔM was comparable for all of them. Significant increase in roughness was observed only for Vitremer and Ketac N100. At the end of the brushing cycle, just Vitremer presented surface roughness greater than the composite resin. Conclusion: All glass ionomer cements showed significant weight loss after 10,000 cycles of brushing. However, only Vitremer showed an increase of roughness greater than the Z350 resin, while the nanoparticulate cement Ketac N100 showed a smooth surface comparable to the composite.

Desempenho produtivo e respostas hematológicas da Tilápia- do-Nilo submetida a diferentes níveis de proteína e condições de estresse

Pós-graduação em Zootecnia - FMVZ

L-Aminoacid oxidase from bothrops leucurus venom Induces nephrotoxicity via apoptosis and necrosis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Experimental Model of Arthritis Induced by Paracoccidioides brasiliensis in Rats

Paracoccidioidomycosis (PCM), a disease caused by the fungus Paracoccidioides brasiliensis (Pb), is highly prevalent in Brazil, where it is the principal cause of death by systemic mycoses. The disease primarily affects men aged 30-50 year old and usually starts as a pulmonary focus and then may spread to other organs and systems, including the joints. The present study aimed to develop an experimental model of paracoccidioidomycotic arthritis. Two-month-old male Wistar rats (n = 48) were used, divided in 6 groups: test groups EG/15 and EG/45 (received one dose of 100 mu l of saline containing 10(5) Pb viable yeasts in the knee); heat killed Pb-group HK/15 and HK/45 (received a suspension of 10(5) Pb nonviable yeasts in the knee) and control groups CG/15 and CG/45 (received only sterile saline in the knee). The rats were killed 15 and 45 days postinoculation. In contrast with the control rats, the histopathology of the joints of rats of the test groups (EG/15 and EG/45) revealed a picture of well-established PCM arthritis characterized by extensive sclerosing granulomatous inflammation with numerous multiple budding fungal cells. The X-ray examination revealed joint alterations in these groups. Only metabolic active fungi evoked inflammation. The experimental model was able to induce fungal arthritis in the knees of the rats infected with metabolic active P. brasiliensis. The disease tended to be regressive and restrained by the immune system. No evidence of fungal dissemination to the lungs was observed.