Chemomodulation of human dendritic cell function by antineoplastic agents in low noncytotoxic concentrations

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Synthetic and natural polycations for gene therapy: State of the art and new perspectives

Currently, the major drawback of gene therapy is the gene transfection rate. The two main types of vectors that. are used in gene therapy are based on viral or non-viral gene delivery systems. There are several non-viral systems that can be used to transfer foreign genetic material into the human body. In order to do so, the DNA to be transferred must escape the processes that affect the disposition of macromolecules. These processes include the interaction with blood components, vascular endothelial cells and uptake by the reticuloendothelial system. Furthermore, the degradation of therapeutic DNA by serum nucleases is also a potential obstacle for functional delivery to the target cell. Cationic polymers have a great potential for DNA complexation and may be useful as non-viral vectors for gene therapy applications. The objective of this review was to address the state of the art in gene therapy using synthetic and natural polycations and the latest strategies to improve the efficiency of gene transfer into the cell.

Vehicle influence on calcium hydroxide pastes diffusion in human and bovine teeth

The purpose of this study was to compare the pH and calcium ion liberation after use of calcium hydroxide pastes with different paste vehicles in human or bovine teeth. Ninety-two single-rooted human and bovine roots were used. The roots were instrumented and an external cavity preparation was performed. The roots were divided in to human and bovine groups. Each group was subdivided into four subgroups (SB) according to the vehicle:SB1, detergent; SB2, saline; SB3, polyethylenoglycol + camphorated paramonochlorophenol (Calen PMCC) and SB4, polyethylenoglycol + furacyn paramonochlorophenol (FPMC). Specimens were immersed into saline solution at 37 degrees C and after 7 and 14 days pH and calcium ion measurements were made. The results were analyzed by ANOVA and Tukey tests (P < 0.05). There was no statistical difference between bovine and human teeth in the pH analysis (P < 0.05), but bovine teeth provided larger calcium ion liberation than human teeth. Calen PMCC was statistically more effective for pH increase and calcium ion liberation in all analyses, followed by FPMC and saline. Detergent showed the lowest pH alterations and calcium ion liberation. The period of 14 days showed more calcium ionic liberation than the 7-day period.

Human chromosome aberrations induced in vitro by Paracoccidioides brasiliensis glycoproteic component (GP 43)

The in vitro cytogenetic effects of the 43-kDa molecular mass exocellular glycoproteic component (GP 43) from Paracoccidioides brasiliensis were studied in cultures from human lymphocytes. The sample included 10 healthy, white, non-smoking, non-related males (mean age of 31.3 ± 8.2 years). Besides the control, three concentrations of GP 43 (0.125, 1.25 and 5 μg/ml) were used. In each group, around 1000 cells were examined in search of chromosome aberrations, and 30,000 metaphases were analysed for the determination of the Mitotic Index. The authors conclude that GP 43 most probably causes inhibition of the cell cycle and aneugenic and clastogenic effects.

Kinetics and crystal structure of human purine nucleoside phosphorylase in complex with 7-methyl-6-thio-guanosine

Purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of nucleosides and deoxynucleosides, generating ribose 1-phosphate and the purine base, which is an important step of purine catabolism pathway. The lack of such an activity in humans, owing to a genetic disorder, causes T-cell impairment, and drugs that inhibit this enzyme may have the potential of being utilized as modulators of the immunological system to treat leukemia, autoimmune diseases, and rejection in organ transplantation. Here, we describe kinetics and crystal structure of human PNP in complex with 7-methyl-6-thio-guanosine, a synthetic substrate, which is largely used in activity assays. Analysis of the structure identifies different protein conformational changes upon ligand binding, and comparison of kinetic and structural data permits an understanding of the effects of atomic substitution on key positions of the synthetic substrate and their consequences to enzyme binding and catalysis. Such knowledge may be helpful in designing new PNP inhibitors. © 2005 Elsevier Inc. All rights reserved.

Pro- and anti-inflammatory cytokines produced by human monocytes challenged in vitro with Paracoccidioides brasiliensis

Monocytes and macrophages play a central role in innate and adaptive immune response against systemic fungal infections. Imbalances in suppressor or stimulatory cytokine secretion caused by these cells may influence disease development, microorganism death, and the nature of the adaptive immune response. This study analyzed the monocyte cytokine profiles of healthy individuals challenged with high and low virulent strains of P. brasiliensis and mRNA cytokine expression kinetics by reverse transcription polymerase chain reaction (RT-PCR). Peripheral blood monocytes from healthy volunteers were cultured in vitro with and without virulent (Pb18) or low virulence (Pb265) strains from P. brasiliensis viable yeast cells. Interleukin-1 beta (IL-1β), IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-α), and transforming growth factor-beta (TGF-β1) were measured in culture supernatants by enzyme immunoassay (ELISA), and mRNA cytokine expression was determined by RT-PCR at 0, 4, 8, 12, 18 and 48 hr. Both P. brasiliensis strains induced monocyte production of IL-1β, IL-6, IL-10 and TNF-α. Pb18 induced higher levels of IL-1β, IL-6, and IL-10 than Pb265. IL-8 and TGF-β1 levels were not significantly different from those cultured without stimulus. The mRNA cytokine expression was similar to supernatant cytokines measured by ELISA. In vitro monocyte challenge with virulent P. brasiliensis strain induces earlier and higher levels of pro- and anti-inflammatory cytokines than low virulence strain.

Photoprotective and antioxidant effects of Rhubarb: Inhibitory action on tyrosinase and tyrosine kinase activities and TNF-α, IL-1α and α-MSH production in human melanocytes

Background: Exposure to ultraviolet (UV) radiation causes various forms of acute and chronic skin damage, including immunosuppression, inflammation, premature aging and photodamage. Furthermore, it induces the generation of reactive oxygen species, produces proinflammatory cytokines and melanocyte-stimulating hormone (MSH) and increases tyrosinase activity. The aim of this study was to evaluate the potential photoprotective effects of Rheum rhaponticum L. rhizome extract on human UV-stimulated melanocytes.Methods: The effects of Rheum rhaponticum rhizome extract on tyrosine kinase activity, and on interleukin-1α (IL-1α), tumour necrosis factor α (TNF-α), and α-MSH production in human epidermal melanocytes were evaluated under UV-stimulated and non-stimulated conditions. Antioxidant activity was evaluated by lipid peroxidation and 1,1-dyphenyl-2-picryl-hydrazyl (DPPH) assays, while anti-tyrosinase activity was evaluated by the mushroom tyrosinase method.Results: Rheum rhaponticum L. rhizome extract showed in vitro antioxidant properties against lipid peroxidation, free radical scavenging and anti-tyrosinase activities, and inhibited the production of IL-1α, TNF-α, α-MSH, and tyrosine kinase activity in melanocytes subjected to UV radiation.Conclusions: These results support the inclusion of Rheum rhaponticum L. rhizome extract into cosmetic, sunscreen and skin care products for the prevention or reduction of photodamage. © 2013 Silveira et al; licensee BioMed Central Ltd.

International migration, human rights and development in Latin America and the Caribbean: summary and conclusions

Includes bibliography

An assessment of the economic impact of climate change on the coastal and human settlements Sector in Barbados

This study assesses the potential economic impact of climate change on coastal human settlements in the Caribbean, with specific reference to Barbados, and evaluates the costs and benefits of undertaking various adaptation strategies. The aim is to assist Caribbean territories in developing the strategies and capacity needed to deal with the potential impact of severe weather events that are anticipated to occur with increased frequency and intensity as a result of climate change. Some of the key anticipated manifestations of climate change for the Caribbean include elevated air and sea-surface temperatures, sea-level rise, possible changes in extreme events and a reduction in freshwater resources.This research focuses on how human settlements distributed along the coast of Guyana, especially those in low elevation coastal zones (LECZ)are affected by these impacts. Focusing on three potential transmission sources - sea-level rise, stronger storm hazards and increased precipitation – the study considers the vulnerability of populations in the LECZ areas and estimates the overall threat posed by climate change to coastal populations and infrastructure. Vulnerability to climate change (measured as exposed assets) was estimated for four emission scenarios as outlined by the Special Report on Emissions Scenarios (SRES), namely the A1, A2, B1 and B2 scenarios for the period 2010 to 2100 and as detailed by the Intergovernmental Panel on Climate Change (IPCC), using global circulation models (GCM) and storm surge hazard maps.

Cymbopogon martinii essential oil and geraniol at noncytotoxic concentrations exerted immunomodulatory/anti-inflammatory effects in human monocytes

ObjectivesIn traditional medicine, plants have formed the basis of sophisticated systems that have been in existence for thousands of years and still provide mankind with new remedies. Cymbopogon martinii, known as palmarosa, has been used in aromatherapy as a skin tonic due to its antimicrobial properties. It has also used in Ayurvedic medicine for skin problems and to relieve nerve pain. The immunomodulatory action of C.martinii essential oil (EO) and geraniol was evaluated regarding the production of pro- and anti-inflammatory cytokines (tumour necrosis factor (TNF)- and IL-10, respectively) by human monocytes in vitro.MethodsMonocyte cultures were incubated with EO or geraniol. After 18h, cytotoxicity assays were performed using 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide method, and cytokine production was determined by ELISA.Key findingsThe variables showed no cytotoxic effects on monocytes. TNF- production was not affected by C.martinii and geraniol, and only the concentration of 5g/ml of C.martinii stimulated its production. On the other hand, all concentrations of C.martinii and geraniol increased IL-10 production by human monocytes.ConclusionsData showed that noncytotoxic concentrations of EO and geraniol exerted an anti-inflammatory action by increasing IL-10 production; moreover, geraniol seemed to be probably responsible for EO immunomodulatory activity in our assay condition.

BILL E. KUNKLE INTERDISCIPLINARY BEEF SYMPOSIUM: Temperament and acclimation to human handling influence growth, health, and reproductive responses in Bos taurus and Bos indicus cattle

Temperament in cattle is defined as the fear-related behavioral responses when exposed to human handling. Our group evaluates cattle temperament using 1) chute score on a 1 to 5 scale that increases according to excitable behavior during restraint in a squeeze chute, 2) exit velocity (speed of an animal exiting the squeeze chute), 3) exit score (dividing cattle according to exit velocity into quintiles using a 1 to 5 scale where 1 = cattle in the slowest quintile and 5 = cattle in the fastest quintile), and 4) temperament score (average of chute and exit scores). Subsequently, cattle are assigned a temperament type of adequate temperament (ADQ; temperament score <= 3) or excitable temperament (EXC; temperament score > 3). To assess the impacts of temperament on various beef production systems, our group associated these evaluation criteria with productive, reproductive, and health characteristics of Bos taurus and Bos indicus-influenced cattle. As expected, EXC cattle had greater plasma cortisol vs. ADQ cattle during handling, independent of breed type (B. indicus x B. taurus, P < 0.01; B. taurus, P < 0.01; B. indicus, P = 0.04) or age (cows, P < 0.01; heifers or steers, P < 0.01). In regards to reproduction, EXC females had reduced annual pregnancy rates vs. ADQ cohorts across breed types (B. taurus, P = 0.03; B. indicus, P = 0.05). Moreover, B. taurus EXC cows also had decreased calving rate (P = 0.04), weaning rate (P = 0.09), and kilograms of calf weaned/cow exposed to breeding (P = 0.08) vs. ADQ cohorts. In regards to feedlot cattle, B. indicus EXC steers had reduced ADG (P = 0.02) and G:F (P = 0.03) during a 109-d finishing period compared with ADQ cohorts. Bos taurus EXC cattle had reduced weaning BW (P = 0.04), greater acute-phase protein response on feedlot entry (P <= 0.05), impaired feedlot receiving ADG (P = 0.05), and reduced carcass weight (P = 0.07) vs. ADQ cohorts. Acclimating B. indicus x B. taurus or B. taurus heifers to human handling improved temperament (P <= 0.02), reduced plasma cortisol (P < 0.01), and hastened puberty attainment (P <= 0.02). However, no benefits were observed when mature cows or feeder cattle were acclimated to human handling. In conclusion, temperament impacts productive, reproductive, and health characteristics of beef cattle independent of breed type. Hence, strategies to improve herd temperament are imperative for optimal production efficiency of beef operations based on B. taurus and B. indicus-influenced cattle.

Ciência da carne: a linguagem gráfica da anatomia humana

This monograph seeks to provide an exposition and theoretical examination of Ciência da Carne (“Science of the Flesh”), a series of artworks in woodcut printing executed after research into the artistic aspects of Human Anatomy, done throughout the Graduate Course in Visual Arts at UNESP’s Art Institute. Traditional procedures of naturalistic representation of the human figure often adopt the scientific basis of Anatomy as a means of interpreting the surface contours of the body from its inside out. The historical connection between Anatomy and Art, however, is not merely accidental, for it is integral to the development of both disciplines, which find themselves deeply related in the human impulse for self-discovery and reinvention of its own likeness. The series of artworks collected in Ciência da Carne explores, through the particular graphical language provided by woodcut printing, abstract arrangements of isolated anatomical elements, at once removed from the context of traditional figurative representation and from the didactic goals of medical illustration.

Road wanderers in Brazil: a study on modern psychosocial human mobility

Human mobility patterns are quite diverse nowadays and a very singular, extreme pattern is seen in the Brazilian scene: road wandering. Road wanderers are individuals who leave their home, family, work and other territories of a settled life and throw themselves into a life of solitary wandering along Brazilian highways. This study aimed to describe the lifestyle of road wanderers, investigate the reasons that led them choose this way of living and understand it against a background of modern human mobility patterns. A total of 63 interviews were conducted with individuals wandering on road shoulders. We found road wandering is associated with the following determinants: poverty; unemployment; marital conflicts; emotional suffering following the loss of loved ones; desires for adventure and freedom; and cultural symbols related to journey, migration, exodus and other modes of displacement. Despite its particularities, road wandering can be understood as a way of human mobility in the modern world.

The modulatory effects of caffeic acid on human monocytes and its involvement in propolis action

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

First genome sequence of St. Louis encephalitis virus (SLEV) isolated from a human in Brazil

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