Avaliação da resposta anti-inflamatória em pacientes com anemia falciforme : o papel da interleucina-27 e da interleucina-37

Orientadores: Maria Heloisa de Souza Lima Blotta, Magnun Nueldo Nunes dos SantosDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: Introdução e objetivo: A reposta inflamatória está envolvida na patogênese de muitas complicações vistas em pacientes com anemia falciforme (AF). O objetivo deste trabalho é avaliar os níveis séricos de duas citocinas anti-inflamatórias descobertas recentes, a IL-27 e IL-37, e algumas citocinas inflamatórias em pacientes brasileiros com AF em tratamento com hidroxiureia (HU) e comparar com pacientes sem este tratamento e indivíduos controle. Além disso, demostrar o efeito da IL-27, IL-37 e heme in vitro na secreção de IL-8 por neutrófilos e monócitos humanos. Métodos: Estudo transversal com 82 pacientes com AF (35 sem tratamento com HU e 47 em tratamento com HU) com a doença estável e 49 indivíduos controle. Os dados clínicos foram obtidos por entrevista e de prontuários. Os níveis séricos de IL-27, IL-37, TGF-?, TNF-?, IL-1?, IL-6 e IL-8 foram dosados por ELISA. Neutrófilos e monócitos foram isolados de indivíduos saudáveis e cultivados separadamente com ou sem citocinas (IL-27 e IL-37) e heme. As citocinas pró inflamatórias no sobrenadante de cultura foram detectadas por ELISA. Resultados: Os níveis plasmáticos de IL-27, IL-37, IL-1?, IL-6 e IL-8 em pacientes em tratamento com HU estão significativamente elevados em comparação a controles HbAA. Não houve diferença nos níveis séricos de citocinas pró e anti-inflamatórias, exceto IL-8, em pacientes tratados com HU comparados a indivíduos controles. IL-27 e IL-37 estão correlacionadas positivamente em pacientes HbSS com e sem tratamento com HU. A produção de IL-8 in vitro por neutrófilos e monócitos pré tratados com IL-27 e IL-37 foi significativamente inibida apesar da adição de heme. Conclusão: Nossos achados demonstram que a IL-27 e IL-37 estão elevadas em pacientes com AF sem tratamento com HU. As citocinas IL-27 e IL-37 podem exercer um papel regulatório nas vias pró inflamatórias, como sugerido pelos experimentos in vitro. Este papel é provavelmente suficiente em prevenir posteriores danos celulares e teciduais, mas não potente o suficiente para prevenir inflamação. Assim, IL-27 e IL-37 podem ser potenciais alvo imunes para melhorar as complicações associadas com elevação do heme como visto em AF e outras anemias hemolíticasAbstract: Background and objective: Inflammation has been implicated in the pathogenesis of most complications seen in Sickle cell anemia (SCA) patients. This project aimed to evaluate serum levels of two newly discovered anti-inflammatory cytokines IL-27 and IL-37 and some pro-inflammatory cytokines among Brazilian SCA patients that are hydroxurea-naive and compared with hydroxyurea-treated patients and HbAA controls. Furthermore, to demonstrate the effect of IL-27, IL-37 and heme on in vitro secretion of IL-8 in human neutrophils and monocytes. Methods: It is a cross-sectional study of 82 consenting SCA (35 hydroxyurea-naïve HbSS and 47 hydroxyurea-treated HbSS) patients in steady state and 49 HbAA consenting individuals. Their clinical details were obtained by interview and from patients¿ records. The serum levels of IL-27, IL-37, TGF-?, TNF-?, IL-1?, IL-6 and IL-8 were quantified by ELISA. Neutrophils and monocytes were isolated from healthy controls, cultured separately without or with cytokines (IL-27 and IL-37) and heme. The pro-inflammatory cytokines in the supernatant were detected by ELISA, Results: Serum levels of IL-27, IL-37, IL-1?, IL-6 and IL-8 in hydroxyurea- naïve SCA patients were significantly elevated compared to HbAA controls There was no significant difference in the serum levels of both anti- and pro-inflammatory cytokines except IL-8 in the HU-treated SCA patients compared to controls. IL-27 and IL-37 were positively correlated in both HU-naive and hydroxyurea-treated HbSS patients. In vitro IL-8 production by IL-27 and IL-37 pre-treated neutrophils and monocytes was significantly inhibited despite addition of heme. Conclusions: Our findings show that IL-27 and IL-37 are elevated in HU-naïve patients. The study support that the use of HU did not significantly alter serum levels of anti- and pro-inflammatory cytokines except IL-8 in SCA patients. IL-27 and IL-37 may play a regulatory role on the pro-inflammatory pathways, as suggested by the in vitro studies. This role is probably sufficient to prevent further cellular or tissue damage but not potent enough to prevent inflammation. Thus, IL-27 and IL-37 may be potential immuno-targets to ameliorate complications associated with elevated heme as seen in SCA and other hemolytic anemiasMestradoPatologia ClinicaMestre em Ciências Médicas400005/2013-1CNP

Studies of harnessing quality attributes of condiment powder (IRU) processed from soy (Glycine max) and African locust bean (Parkia biglobosa) seeds

This study harnessed the quality attributes of condiment powder (iru) processed from soy and African locust bean seeds using calabash and plastic as fermenting containers. The soy and African locust bean-condiment powders were comparatively evaluated with referencecondiment based upon storability for 8-weeks on moisture gain or loss and microbial counts, and 3-weeks colour evaluation were carried out. Sensory analysis was done using students of the Department of Food Technology, University of Ibadan. The design of the experiment was carried out using completely randomized design. The results revealed increase in moisture throughout the weekly storage study as the concluding 8-week showed highest in referencecondiment(14.78 %) and lower in soy-condiment powder (10.03 %) produced in plastic. Microbial count ranged from 4.74 to 5.07 log10 cfu/mL and no detection of fungi in all condiment powder samples. However, coliform was present only in control-condiment (0.73 log10 cfu/mL). Weekly storage studies on total viable count of soy and African locustcondiment powders ranged from 4.74-5.07 (week 0); 4.93-5.05 (week 1); 4.66-5.47 (week 2); 4.11-5.07 (week 3); 4.20-5.59 (week 4); 4.51-5.76 (week 5); 4.75-5.88 (week 6); 4.01-5.28 (week 7) and 4.48-5.62 (week 8) log10 cfu/mL. The degree of lightness (L*), redness (a*) and yellowness (b*) on soy and locust bean-condiment powders produced in a plastic had optimum scores but lower in reference-condiment. General acceptability was highest in soy-condiment powder produced in plastic. Plastic container can be use for the processing of condiment powder without any adverse effect on the final product. Keywords: African locust bean, soy bean, containers, powdered condiment, moisture gai

Ethnomedicinal Uses and Therapeutic Activities of Piper Guineense: A Review

The use of medicinal plants in most developing countries as therapeutic agents for the maintenance of good health is a widespread practice. One of such plant products is Piper guineense, which is a West African spice used in many folklore medicines and has a number of verified pharmacological activities. Proximate analysis reveals that the plant contains crude protein, fat, carbohydrate, vitamins and minerals while preliminary phytochemical screening and gas chromatography-mass spectrophotoscopy of the methanol leaf and seed extract of Piper guineense revealed the presence of several constituents such as alkaloids, glycosides, tannins, flavonoids, terpenes; sesquiterpenoids and monoterpenoids, saponins and secondary metabolites such as Aromadendrene, 1,6,10- Dodecatriene,7,11-dimethyl-3-methylene and piperine, piperidine amongst other secondary metabolites. Studies have revealed that Piper guineense possess several pharmacological and therapeutic properties such as anti-oxidant, anti-microbial, aphrodisiac, anti-parasitic, antiinflammatory, anti-convulsant, molluscicidal, oestrogenic and oxytocic properties. This paper provides a review on the morphology, physicochemical and phytochemical constituents, ethnomedicinal and scientifically proven therapeutic activities of Piper guineense

DETERMINING THE INDIVIDUAL SIGNIFICANT CONTRIBUTION OF PUBLIC AND PRIVATE SECTOR IN HOUSING DELIVERY IN NIGERIA

One of the greatest challenge confronting both rural and urban residents in Nigeria is the need to provide adequate shelter. This study examined the individual significant contribution of the public and private sector in public-private partnerships (PPP) in housing contracts in Ogun State, Nigeria. A field survey was conducted in government ministries (public sector) and some selected professionals (private sector) within the study area. Information gathered from both primary and secondary data was used to determine the significant contribution of the public and private sector in housing delivery. Questionnaires were distributed through systematic sampling method to 58 respondents in both private and public sector participating in PPP housing production in the study area. Result showed that the significant contribution of the public sector in PPP housing provision in Nigeria is the provision of land while the private sector contributes significantly high percentage of finance, manpower and technical support. The study recommended that for successful implementation of PPP housing projects, all tiers of government must strive to complement the weaknesses of the public sector with the strengths of the private sector. Furthermore, since the private sector provides bulk of the finance for PPP housing projects, government should provide a more conducive economic environment to attract more private sector investors

Multiple Bone and Joint Diseases in a Nigerian Sickle Cell Anaemia: a Case Report

This case highlights the fact that bone involvement is the commonest clinical manifestation of Sickle Cell Disease (SCD) both in the acute settings such as painful vaso-occlusive crisis (VOC) and as a source of chronic, progressive debility such as avascular necrosis (AVN), chronic osteomyelitis and fixed flexion deformity of joints

RESIDENTS’ FACILITIES SATISFACTION IN HOUSING PROJECT DELIVERED BY PUBLIC PRIVATE PARTNERSHIP (PPP) IN OGUN STATE, NIGERIA

Public-private partnership in housing development provide conducive housing environment through provision of services, good and quality facilities, easy access to social amenities, good security arrangement among others. It is on this basis that this study examined residents’ satisfaction of facilities in housing projects delivered by public private partnership. A field survey was conducted in three existing housing estates delivered through PPP within the study area. The information gathered from both the secondary and primary data were used to analyze occupant’s satisfaction of facilities available in housing project delivered by PPP. Questionnaires were distributed through systematic sampling method to 224 respondents in the three existing housing estates in the study area. Result showed that Year of tenure, size of house hold, provision of facilities, security of life and properties, location of resident, space allocation, proximity to work place were some of the factors significantly contributed to occupier satisfaction of facilities available in a PPP driven housing estate .The study recommended that for successful implementation of the PPP housing project to meet the desired satisfaction of any occupier, the government should ensure that all the necessary infrastructural facilities and services like good road, electricity, school, health centre etc. be provided first before building production commence on the estate. Moreover, recreational facilities lacking in most of the estates should be provided so that residents of the estate would not need to travel miles to access these facilities

Desempenho de crescimento e resposta fisiológica de leitões desmamados alimentados com dieta suplementada com novos fitogênicos.

The aim of this experiment was to investigate the growth performance and physiological response of weaned pigs fed diets supplemented with a novel phytogenics (FCTNC). A total of 100 cross bred male pigs (Landrace × Duroc) with an initial weight of 6.31 ± 0.25 kg and weaned at 21 days were individually housed in a semi-open sided pens. Pigs were distributed into five treatments groups with five replicates, each replicates comprises of 20 pigs. Experimental diets were adequate in all nutrients recommended by NRC (2012). Treatment one (T1): basal diet without antibiotics; T2 (basal diet with neomycin at 1.5 g/kg-1); T3, T4 and T5 were fed basal diet with 5 g/kg-1, 10 g/kg-1 and 15 g/kg-1 respectively. Feed and water were offered unrestricted throughout the 56 days trial. Result revealed that there was effect of treatments (P ˂ 0.05) in average body weight gain (ADG), daily feed intake (ADFI), mortality and feed conversion ratio (FCR). Pigs in T4 (24.54 kg) and T5 (24.22 kg) had the highest weight gain, intermediate in T2 (21.55 kg) and T3 (22.51 kg) and lowest in T1 (12.83 kg) (P ˂ 0.05). There was a remarkable improvement in all the immune parameters examined among pigs fed FCTNC (P ˂ 0.05). Microbial population of Escherichia coli and Salmonella spp decreased as the level of FCTNC increases (P ˂ 0.05). Conversely, Lactobacillus spp count were highest in T4 and T5 relative to the other treatments. Haematological parameters were significantly influenced (P ˂ 0.05) by the treatments. However, all values were within the normal range for a clinically healthy pigs. The study established that FCTNC could be fed to weaned pigs up to 15 g/kg-1 without having any negative effect on the health of animals.El objetivo de este experimento fue investigar el desempeño zootécnico y la respuesta fisiológica de lechones destetados alimentados con dietas suplementadas con un nuevo fitogénico (FCTNC). Un total de 100 cerdos machos mestizos (Landrace × Duroc) con peso inicial de 6,31 ± 0,25 kg y destetados a los 21 días se alojaron individualmente en corrales semiabiertos. Los cerdos se asignaron a cinco grupos de tratamiento con cinco repeticiones, cada una de las cuales constaba de 20 cerdos. Las dietas experimentales fueron adecuadas en todos los nutrientes recomendados por la NRC (2012). Tratamiento uno (T1): dieta basal sin antibióticos; T2 (dieta basal con neomicina a 1,5 g/kg-1); T3, T4 y T5 recibieron dieta basal con 5 g/kg-1, 10 g/kg-1 y 15 g/kg-1, respectivamente. Se ofreció alimento y agua sin restricciones durante los 56 días del experimento. Los resultados revelaron que hubo un efecto de los tratamientos (P ˂ 0.05) sobre la ganancia de peso corporal promedio (GMD), el consumo diario de alimento (ADFI), la mortalidad y la conversión alimenticia (CA). Los cerdos en T4 (24,54 kg) y T5 (24,22 kg) tuvieron la mayor ganancia de peso, intermedia en T2 (21,55 kg) y T3 (22,51 kg) y menor en T1 (12,83 kg) (P ˂ 0,05). Hubo una mejora notable en todos los parámetros inmunológicos examinados entre los cerdos alimentados con FCTNC (P ˂ 0.05). La población microbiana de Escherichia coli y Salmonella spp disminuyó con el aumento del nivel de FCTNC (P ˂ 0.05). Por otro lado, el conteo de Lactobacillus spp fue mayor en T4 y T5 en comparación con los demás tratamientos. Los parámetros hematológicos fueron influenciados significativamente (P ˂ 0.05) por los tratamientos. Sin embargo, todos los valores estuvieron dentro del rango normal para cerdos clínicamente sanos. El estudio estableció que FCTNC puede administrarse a lechones destetados hasta 15 g/kg-1 sin tener ningún efecto negativo sobre la salud de los animales.O objetivo deste experimento foi investigar o desempenho zootécnico e a resposta fisiológica de leitões desmamados alimentados com dietas suplementadas com um novo fitogênico (FCTNC). Um total de 100 suínos machos mestiços (Landrace × Duroc) com peso inicial de 6,31 ± 0,25 kg e desmamados aos 21 dias foram alojados individualmente em baias semiabertas. Os porcos foram distribuídos em cinco grupos de tratamentos com cinco réplicas, cada réplica composta por 20 porcos. As dietas experimentais foram adequadas em todos os nutrientes recomendados pelo NRC (2012). Tratamento um (T1): dieta basal sem antibióticos; T2 (dieta basal com neomicina a 1,5 g/kg-1); T3, T4 e T5 receberam dieta basal com 5 g/kg-1, 10 g/kg-1 e 15 g/kg-1, respectivamente. A ração e a água foram oferecidas sem restrições durante os 56 dias de experiência. Os resultados revelaram que houve efeito dos tratamentos (P ˂ 0,05) no ganho médio de peso corporal (GMD), consumo diário de ração (ADFI), mortalidade e conversão alimentar (CA). Suínos em T4 (24,54 kg) e T5 (24,22 kg) tiveram o maior ganho de peso, intermediário em T2 (21,55 kg) e T3 (22,51 kg) e menor em T1 (12,83 kg) (P ˂ 0,05). Houve uma melhoria notável em todos os parâmetros imunológicos examinados entre os porcos alimentados com FCTNC (P ˂ 0,05). A população microbiana de Escherichia coli e Salmonella spp diminuiu com o aumento do nível de FCTNC (P ˂ 0,05). Por outro lado, a contagem de Lactobacillus spp foi maior em T4 e T5 em relação aos outros tratamentos. Os parâmetros hematológicos foram significativamente influenciados (P ˂ 0,05) pelos tratamentos. No entanto, todos os valores estavam dentro do intervalo normal para porcos clinicamente saudáveis. O estudo estabeleceu que a FCTNC pode ser fornecida a leitões desmamados até 15 g/kg-1 sem ter qualquer efeito negativo na saúde dos animais

Development of a Hybridized Model for Determining the Degree of Polymerization of Power Transformers

Power transformers have been described as an important equipment of electrical switchyard in which its failure results in long hours of outage. Some of the existing models for determining the Degree of Polymerization (DP) of power transformers were based on singular parameter which is not sufficient for the assessment of power transformers’ lifespan. This research paper therefore developed a hybridized model for determining the degree of polymerization of power transformers. The study employed the use 2-Furaldehyde (2FAL) content values of 0.5 ppm to 10ppm in determining the DP value and simulation was carried out using MATLAB. The result was compared with existing DP model for effectiveness of the Hybridized DP model. The developed model yielded a DP range of 247 ≤ DP ≤ 1184 based on a constant hotspot temperature of 1100C and the values of activation energy and pre-exponential factors used. The results from this research presented a better method of determining the Degree of Polymerization of power transformer compared to the existing method. Therefore, the Hybridized DP model developed is more sufficient for the evaluation of lifespan of power transformers. Keywords: Power Transformers, Electrical Switchyard, Lifespan, Degree of Polymerization, Statistical Tools, Power Failure, Outages. DOI: 10.7176/ISDE/12-6-04 Publication date:October 31st 2022

Impaired hemoglobin clearance by sinusoidal endothelium promotes vaso-occlusion and liver injury in sickle cell disease

Sickle cell disease (SCD) is a monogenic disorder that affects 100,000 African-Americans and millions of people worldwide. Intra-erythrocytic polymerization of sickle hemoglobin (HbS) promotes erythrocyte sickling, impaired rheology, ischemia and hemolysis, leading to the development of progressive liver injury in SCD. Liver-resident macrophages and monocytes are known to enable the clearance of HbS; however, the role of liver sinusoidal endothelial cells (LSEC) in HbS clearance and liver injury in SCD remains unknown. Using real-time intravital (in vivo) imaging in mice liver as well as flow cytometric analysis and confocal imaging of primary human LSEC, we show for the first time that liver injury in SCD is associated with accumulation of HbS and iron in the LSEC, leading to senescence of these cells. Hemoglobin uptake by LSEC was mediated by micropinocytosis. Hepatic monocytes were observed to attenuate LSEC senescence by accelerating HbS clearance in the liver of SCD mice; however, this protection was impaired in P-selectin-deficient SCD mice secondary to reduced monocyte recruitment in the liver. These findings are the first to suggest that LSEC contribute to HbS clearance and HbS-induced LSEC senescence promotes progressive liver injury in SCD mice. Our results provide a novel insight into the pathogenesis of hemolysis-induced chronic liver injury in SCD caused by LSEC senescence. Identifying the regulators of LSEC-mediated HbS clearance may lead to new therapies to prevent the progression of liver injury in SCD