Patterns of injury and violence in Yaoundé Cameroon: an analysis of hospital data.

BackgroundInjuries are quickly becoming a leading cause of death globally, disproportionately affecting sub-Saharan Africa, where reports on the epidemiology of injuries are extremely limited. Reports on the patterns and frequency of injuries are available from Cameroon are also scarce. This study explores the patterns of trauma seen at the emergency ward of the busiest trauma center in Cameroon's capital city.Materials and methodsAdministrative records from January 1, 2007, through December 31, 2007, were retrospectively reviewed; information on age, gender, mechanism of injury, and outcome was abstracted for all trauma patients presenting to the emergency ward. Univariate analysis was performed to assess patterns of injuries in terms of mechanism, date, age, and gender. Bivariate analysis was used to explore potential relationships between demographic variables and mechanism of injury.ResultsA total of 6,234 injured people were seen at the Central Hospital of Yaoundé's emergency ward during the year 2007. Males comprised 71% of those injured, and the mean age of injured patients was 29 years (SD = 14.9). Nearly 60% of the injuries were due to road traffic accidents, 46% of which involved a pedestrian. Intentional injuries were the second most common mechanism of injury (22.5%), 55% of which involved unarmed assault. Patients injured in falls were more likely to be admitted to the hospital (p < 0.001), whereas patients suffering intentional injuries and bites were less likely to be hospitalized (p < 0.001). Males were significantly more likely to be admitted than females (p < 0.001)DiscussionPatterns in terms of age, gender, and mechanism of injury are similar to reports from other countries from the same geographic region, but the magnitude of cases reported is high for a single institution in an African city the size of Yaoundé. As the burden of disease is predicted to increase dramatically in sub-Saharan Africa, immediate efforts in prevention and treatment in Cameroon are strongly warranted

Exercise-induced brain plasticity − potential roles of lactate receptor HCA1 in neurogenesis and mood regulation, and neurotrophic factors in stroke

The brain is highly plastic. It responds to changes in the environment by reorganizing pathways, creating new connections, or strengthening existing ones, rewiring itself, as well as by creating new blood vessel and neurons. Brain plasticity is an important part of normal brain function, learning, mood regulation, and a myriad of other processes, and is important in the protection against, and the recovery from, brain diseases such as stroke and mood disorders. Finding ways to regulate neuroplasticity is therefore a hot topic in neuroscience. Exercise has immense effect on physical and mental health and induces neurogenesis and other forms of brain plasticity. Our research group has previously reported that exercise-induced angiogenesis (growth of new blood vessels) in the brain occurs partly via lactate-dependent activation of the hydroxycarboxylic acid receptor 1 (HCA1). To investigate if high-intensity interval training (HIIT) efficiently induced neurogenesis and, if so, whether this occurred via lactate-dependent activation of HCA1, we compared HCA1 knockout (KO) mice and wild-type (WT) mice. In paper 1, we showed that neurogenesis is regulated differently in the two main neurogenic niches in the brain, the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ) of the lateral ventricles. We reported that neurogenesis was regulated by HCA1-activation in the SVZ, since enhanced neurogenesis was observed in response to HIIT in WT mice but not in HCA1 KO mice. Furthermore, L-lactate treatment enhanced neurogenesis in the SVZ of WT mice even more than HIIT, and again the effect was not apparent in HCA1 KO mice. In the SGZ, on the other hand, HIIT induced neurogenesis equally in both genotypes, and L-lactate treatment did not induce neurogenesis in either genotype. This indicates that exerciseinduced neurogenesis in this niche was independent of lactate signaling through HCA1. Since depression has been linked to reduced neuroplasticity and hippocampal neurogenesis, and exercise is known to have antidepressant effects similar to those of antidepressant drugs, we investigated whether the antidepressant effects of exercise were mediated via the HCA1-activation. In paper 2, we showed that two weeks of HIIT or medium-intensity interval exercise (MIIT), equally reduced depression-like behavior in WT mice but not in HCA1 KO mice. After six weeks of exercise, a reduction in depression-like behavior was observed only in response to MIIT, not to HIIT. Interestingly, this effect reached statistical significance only in the WT mice and not in the HCA1 KO mice, implying that HCA1-activation plays a role in mediating this antidepressant effect, and may represent a novel target for antidepressant therapy. Neurogenesis and other forms of brain plasticity are to a large degree regulated by growth factors and are important in the recovery after acute ischemic stroke. In paper 3, we aimed to determine if the plasma levels of key growth factors differed between acute stroke patients and healthy age and gender matched controls. We found that the plasma levels of brain-derived neurotrophic factor (BDNF) and epidermal growth factor (EGF) were significantly lower in stroke patients than in the healthy controls, while the levels of basic fibroblast growth factor (bFGF) and the myokine irisin did not differ. These findings indicate a reduced level of growth factors, presumably consistent with a reduced potential for plasticity and repair, in the condition of stroke where such mechanisms would be needed to prevent permanent brain damage. Interestingly, large individual differences were found in the levels of all growth factors and irisin. Further research is needed to determine whether these differences in growth factor levels, measured in the acute phase of stroke, can be used to predict post-stroke recovery. All in all, the data presented in the present thesis suggest that HCA1-activation contribute to enhancing neurogenesis in the SVZ as well as to the antidepressant effects of exercise. Whether HCA1-activation by intrinsically released lactate in the acute phase of stroke, or treatments with HCA1-agonist would contribute to enhanced recovery after stroke remains to be investigated. Hjernen er svært plastisk. Den reagerer på endringer i miljøet ved å omorganisere nervebaner, skape nye forbindelser, eller styrke eksisterende, samt ved å danne nye blodårer og nerveceller. Hjerneplastisitet er en viktig del av normal hjernefunksjon, læring, regulering av stemningsleie og en rekke andre prosesser. Plastisitet er også viktig i beskyttelsen mot sykdom i hjernen, som for eksempel hjerneslag, og i tilheling etterpå. Måter å regulere nevroplastisitet på er derfor et viktig tema innen nevrovitenskap. Trening har enorm effekt på fysisk og mental helse og øker nevrogenese og andre former for hjerneplastisitet. Vår forskergruppe har tidligere vist at treningsindusert angiogenese (nydannelse av blodårer) i hjernen delvis skjer via laktatavhengig aktivering av hydroksykarboksylsyrereseptor 1 (HCA1). For å undersøke om intervalltrening med høy intensitet (HIIT) effektivt økte nevrogenese, og i så fall om dette skjedde via laktatavhengig aktivering av HCA1, sammenlignet vi HCA1 knockout (KO) mus og villtype (WT) mus. I artikkel 1, viste vi at nevrogenese reguleres forskjellig i de to viktigste nisjene for nevrogenese i hjernen, den subgranulære sonen (SGZ) i hippokampus og den subventrikulære sonen (SVZ) ved de laterale ventriklene. Vi viste at nevrogenese ble regulert av HCA1-aktivering i SVZ, siden økt nevrogenese ble observert som respons på HIIT i WT-mus, men ikke i HCA1 KOmus. Videre økte L-laktatbehandling nevrogenese i SVZ i WT-mus mer enn hva HIIT gjorde, og igjen var effekten fraværende i HCA1 KO-mus. I SGZ, derimot, fant vi at HIIT økte nevrogenese like mye i begge genotyper, mens behandling med L-laktat ikke økte nevrogenese i noen av genotypene. Dette indikerer at treningsindusert nevrogenese i denne nisjen var uavhengig av laktatsignalering gjennom HCA1. Siden depresjon har vært knyttet til redusert nevral plastisitet og hippocampal nevrogenese, og trening er kjent for å ha antidepressive effekter som ligner på det man ser ved antidepressive legemidler, undersøkte vi om de antidepressive effektene av trening ble indusert via HCA1-aktiveringen. I artikkel 2, viser vi at to uker med HIIT eller intervalltrening med medium intensitet (MIIT), begge reduserte depresjonslignende atferd hos WT-mus, men ikke hos HCA1 KO-mus. Etter seks ukers trening ble en reduksjon i depresjonslignende oppførsel observert kun som respons på MIIT, og ikke HIIT. Interessant nok nådde denne effekten statistisk signifikans bare i WT-mus og ikke i HCA1 KO-mus, noe som antyder at HCA1-aktivering har en rolle i å formidle denne antidepressive effekten, og derfor kan representere et nytt mål for antidepressiv terapi. Nevrogenese og andre former for hjerneplastisitet er i stor grad regulert av vekstfaktorer, og er viktige i tilheling etter akutt iskemisk hjerneslag. I artikkel 3, hadde vi som mål å finne ut om plasmanivåene av viktige vekstfaktorer var forskjellige hos akutte hjerneslagpasienter sammenlignet med friske kontroller med samme alder og kjønn. Vi fant at plasmanivåene av ‘brain-derived’ nevrotrofisk faktor (BDNF) og epidermal vekstfaktor (EGF) var signifikant lavere hos slagpasienter enn hos kontrollpersonene, mens nivåene av ‘basic’ fibroblast vekstfaktor (bFGF) og myokinet irisin ikke var forskjellige mellom gruppene. Disse funnene indikerer et redusert nivå av vekstfaktorer, og dermed mulig redusert potensial for plastisitet og tilheling ved hjerneslag der slike mekanismer ville være nødvendig for å forhindre permanent hjerneskade. Interessant nok ble det funnet store individuelle forskjeller i nivåene av alle vekstfaktorer og irisin. Ytterligere forskning er nødvendig for å fastslå om disse forskjellene i vekstfaktornivåer, målt i den akutte fasen av hjerneslag, kan brukes til å forutsi grad av tilheling etter hjerneslag. Alt i alt tyder dataene som er presentert i denne avhandlingen på at HCA1-aktivering bidrar til å øke nevrogenese i SVZ og medierer noen av de antidepressive effektene av trening. Hvorvidt HCA1-aktivering ved endrogen laktat i den akutte fasen av hjerneslag, eller behandlinger med HCA1-agonister, vil bidra til økt tilheling etter hjerneslag gjenstår å undersøke.publishedVersio

FOXP3 mRNA Splice Variants: Potential Biomarkers of Immunosuppression in Kidney Transplant Recipients

Den aldrende befolkning og stigende prævalens af livsstilsrelaterede kroniske sygdomme, herunder hypertension og diabetes, står bag en forventet stigning i prævalensen af nyresygdomme og terminalt nyresvigt globalt. Nyretransplantation er den bedste behandlingsmulighed for egnede patienter, der lider af terminalt nyresvigt. Imidlertid indebærer nyretransplantation et behov for behandling med en kombination af immunsupprimerende lægemidler. Immunsupprimerende lægemidler skal balanceres hos den enkelte nyretransplantationsmodtager (NTM) for at forhindre afstødning af den transplanterede nyre og minimere risikoen for infektion og alvorlige bivirkninger som f.eks. kræft. Aktuelt er der ingen en klinisk biomarkør, der kan angive den kumulative effekt af immunsupprimerende lægemidler på immunsystemet hos NTM'e.Den aldrende befolkning og stigende prævalens af livsstilsrelaterede kroniske sygdomme, herunder hypertension og diabetes, står bag en forventet stigning i prævalensen af nyresygdomme og terminalt nyresvigt globalt. Nyretransplantation er den bedste behandlingsmulighed for egnede patienter, der lider af terminalt nyresvigt. Imidlertid indebærer nyretransplantation et behov for behandling med en kombination af immunsupprimerende lægemidler. Immunsupprimerende lægemidler skal balanceres hos den enkelte nyretransplantationsmodtager (NTM) for at forhindre afstødning af den transplanterede nyre og minimere risikoen for infektion og alvorlige bivirkninger som f.eks. kræft. Aktuelt er der ingen en klinisk biomarkør, der kan angive den kumulative effekt af immunsupprimerende lægemidler på immunsystemet hos NTM'e.I humane T-regulatoriske celler resulterer RNA-splejsning i ekspression af FOXP3 som tre forskellige varianter: fuldlængde FOXP3 (FOXP3fl), som inkluderer alle kodende eksoner; FOXP3, hvor kodende ekson 2 delukkes (FOXP3d2); og FOXP3, hvor kodende eksoner 2 og 7delukkes (FOXP3d2d7). FOXP3fl og FOXP3d2 udgør op til 99 % af alle FOXP3, der produceres i humane T-regulatoriske. For at T-regulatoriske celler skal kunne differentiere og fungere korrekt, skal både FOXP3fl og FOXP3d2 produceres. FOXP3-varianter har muligvis en evne til at indikere graden af immunsuppression hos NTM’e. Denne evne er ikke tidligere blevet undersøgt. I denne ph.d.-afhandling var formålet at udforske potentialet hos FOXP3-varianter som biomarkører for immunsuppression hos NTM'e. For at opnå målet med denne afhandling målte vi niveauer af FOXP3fl-mRNA, FOXP3d2-mRNA, pre-modent mRNA FOXP3 (pre-mRNA FOXP3) og totalt mængde af modent FOXP3-mRNA (Total FOXP3) i perifert blod hos NTM'e transplanteret på Odense Universitetshospital. Inklusionskriterierne bestod af alder over 18 år og evnen til at give informeret samtykke. FOXP3-varianternesmRNA-niveauer blev målt med kvantitativ revers transskription polymerasekædereaktion i blodprøver, der blev indsamlet før og efter transplantation.Artikel IVi testede hypotesen om lave niveauer af FOXP3-varianter kan afspejle nedsat funktion af T-regulatoriske celler og dermed også afspejle dårligere nyretransplantatfunktion hos NTM'e. Denne hypotese blev testet ved at vurdere, om niveauet af FOXP3-varianter, målt én dag og 29 dage efter transplantation, var forbundet med en nedgang i den estimerede glomerulære filtrationshastighed (eGFR) på mere end 5 ml/min/1,73m2 inden for det første år efter transplantation ved hjælp af multivariabel logistisk regression. Vi inkluderede 333 NTM'e i den endelige analyse, hvoraf 132 havde faldende eGFR. Vi observerede lavere FOXP3fl-niveauer dag 1 efter transplantation hos modtagere med faldende eGFR sammenlignet med modtagere med stabil eGFR (logaritmisk værdi -4,13 [IQR -4,50 til -3,84] kontra -4,00 [4,32 til -3,74]; p = 0,02). Associationen mellem dag 1 FOXP3fl-niveauer og faldende eGFR var signifikant i multivariabel analyse, der var justeret for potentielle forstyrrende faktorer (Odds forhold (OR) 0,51; 95% konfidensinterval 0,28 til 0,91; p = 0,02). Når dag 1 FOXP3fl-niveauer blev opdelt i kvartiler, havde modtagere med lavere dag 1 FOXP3fl det højeste niveau affaldende eGFR (p = 0,04). Således konkluderede vi, at lave niveauer af FOXP3flspliced varianter på den første postoperative dag hos NTM’e var forbundet med alvorlig nedgang i eGFR.Artikel IIHypotesen i denne artikel var, at lave niveauer af FOXP3-varianter kan afspejle en nedsat funktion af T-regulatoriske celler, hvilket kan påvirke T-regulatoriske cellers modulation af den inflammatoriske respons til stimuli. Derfor undersøgte vi associationen mellem niveauer af FOXP3-varianter i perifert blod af NTM'e og forlænget inflammatorisk respons som primært endepunkt (dage, hvor C-reaktivt protein (CRP) er over 50 mg/L). Det sekundære endepunkt var sværhedsgraden af det inflammatoriske respons (maksimalt niveau af CRP-stigning). FOXP3-varianter blev målt dag 1 efter transplantation og 29 dage efter transplantation. Dag 1 FOXP3- varianter blev testet for association med det primære og sekundære endepunkt bestemt inden for den første periode (fra to dage efter transplantation indtil 29 dage efter transplantation). Dag 29 FOXP3-varianter blev testet for association med det primære og sekundære endepunkt inden for den anden periode (30 til 57 dage efter transplantation). Af de 507 NTM'e inkluderet i den endelige analyse havde 382 modtagere mindst én CRP-måling &gt;50 mg/L i den første periode, og 69 modtagere havde mindst én CRP-måling &gt;50 mg/L i den anden periode. Vi testede associationen mellem FOXP3-varianter og primært endepunkt ved hjælp af negativ binomial regressionsanalyse og rettede for forstyrrende faktorer. I den første periode fandt vi en signifikant forbindelse mellem lavere niveauer af total FOXP3 og forlænget varighed af CRP-stigning, incidensrate forhold 0,61 (95% konfidensinterval 0,46-0,80), p &lt;0,01. Således konkluderede vi, at lavere niveauer af totalt FOXP3-mRNA i perifert blod af NTM’e er forbundet med forlænget varighed af inflammatoriske reaktioner.Artikel IIIFormålet med denne artikel var at undersøge, om immunsupprimerende lægemidler påvirker FOXP3- varianter forskelligt hos kvindelige og mandlige NTM'e. Dette er relevant, fordi immunsystemets funktion kan variere efter biologisk køn. Dette fremgår f.eks. af den højere risiko for autoimmunitet hos kvinder og den højere risiko for tab af nyretransplantater hos yngre kvindelige NTM'e. Desuden har nylige publikationer rapporteret modstridende resultater om associationen mellem biologisk køn og FOXP3-ekspressionsniveauer. Derfor udførte vi en kønsbaseret observationsanalyse af FOXP3-varianter i kvindelige og mandlige NTM'e. Vi udførte også en kønsbaseret observationsanalyse af FOXP3-varianter i to populationer af raske mennesker. Vi fandt, at normaliserede FOXP3-varianter udtrykkes ens hos 248 NTM'e før, én dag efter, og 29 dage efter transplantation. Vi fandt desuden ens niveauer af normaliserede FOXP3-varianter hos 101 raske nyredonorer. Vi bekræftede resultaterne fra den raske nyredonor-kohorte i en offentligt tilgængelig kohorte af 33 sunde personer (GSE97475). Således konkluderede vi, at normaliserede niveauer af FOXP3-varianter er ens hos sunde mænd og kvinder og hos NTM'e på trods af virkningerne af immunsupprimerende lægemidler.Som konklusion antyder resultaterne af denne ph.d.-afhandling, at perifere blodniveauer af FOXP3-mRNA kan give indsigt i immuntolerance overfor transplanteret væv hos NTM'e og overfor den immunmodulerende effekt af inflammatoriske reaktioner hos NTM'e. Denne indsigt kan indikere et potentiale for FOXP3-varianter som indikatorer for effekten af immunsupprimerende lægemidler på T-regulatoriske cellers funktion hos NTM'e, hvilket resultaterne viser at være ens hos kvindelige og mandlige NTM'e.Increasing age and increasing prevalence of lifestyle induced chronic diseases, such as hypertension and diabetes, are factors influencing the predicted increase in prevalence of kidney dysfunction and end stage kidney disease globally. Kidney transplantation is the best treatment option for eligible patients suffering from end stage kidney disease. However, kidney transplantation entails treatment with a combination of immunosuppressive medicines. Immunosuppressive medicines must be balanced in the individual kidney transplant recipient (KTR) to hinder rejection of the transplanted kidney and to minimize the risk of infection and other serious side effects such as malignancy. Currently, no clinically available biomarker can indicate the cumulative effect of immunosuppressive medicines on the immune systems of KTRs.The forkhead box P3 (FOXP3) transcription factor may help in indicating the level effect of immunosuppressive medicines in KTRs. FOXP3 is mainly produced in a subset of T cells that are crucial for immunotolerance of auto- and alloantigens, known as T regulatory cells. Without FOXP3 expression, T regulatory cells are unable to differentiate or function correctly. T regulatory cell functions are exercised through modulation and suppression of the immune system which ultimately hinders autoimmunity. Another crucial function of the T regulatory cells mediated immunomodulation of the immune system is the hinderance of excessive immune responses to inflammatory stimuli, which protects inflamed tissues from excessive inflammation. The immunosuppressive function of T regulatory cells has also been shown to be crucial for tolerance of transplanted tissues. Furthermore, FOXP3 expression is affected by immunosuppressive medicines commonly used in KTRs either directly or indirectly.In human T regulatory cells, RNA splicing results in expression of FOXP3 as three different splice variants: Full length FOXP3 (FOXP3fl) which includes all coding exons, FOXP3 in which coding exon two is skipped (FOXP3d2), and FOXP3 in which coding exons two and seven are skipped (FOXP3d2d7). FOXP3fl and FOXP3d2 account for up to 99 % of all expressed FOXP3 variants in human T regulatory cells and must be co-expressed in each T regulatory cell for its correct differentiation, homeostasis, and suppressive function. The potential of FOXP3 splice variants to indicate the level of immunosuppression in KTRs have not been investigated previously. In this PhD dissertation, the aim was to explore the potential of FOXP3 splice variants as biomarkers of immunosuppression in KTRs. To achieve this aim, we measured levels of FOXP3fl mRNA, FOXP3d2 mRNA, pre-mature mRNA FOXP3 (pre-mRNA FOXP3) and total mature FOXP3 mRNA (Total FOXP3) in peripheral blood of KTRs transplanted at Odense University Hospital. Inclusion criteria were comprised of age above 18 years, and the ability to provide informed consent. FOXP3 splice variant mRNA levels were measured with quantitative reverse transcription polymerase chain reaction in blood samples collected before and after transplantation.Paper IWe tested the hypothesis that low FOXP3 splice variant levels may reflect impaired T regulatory cell function and therefore worse kidney allograft function in KTRs. This hypothesis was tested by assessing if FOXP3 splice variant levels, measured one day and 29 days post-transplant, were associated with the decline in estimated glomerular filtration rate (eGFR) of more than 5 ml/min/1.73m2 within the first-year post-transplant using multivariable logistic regression. We included 333 KTRs in the final analysis, 132 of which had declining eGFR. We observed lower FOXP3fl levels, day one post-transplant, in recipients with declining eGFR compared to recipients with stable eGFR, (logarithmic value -4.13 [IQR -4.50 to -3.84] vs -4.00 [ 4.32 to -3.74], p = 0.02). The association between day one FOXP3fl levels and declining eGFR was significant in multivariable analysis adjusted for potential confounding factors (Odds Ratio (OR) 0.51, 95% confidence interval 0.28 to 0.91: p = 0.02). When stratifying day one FOXP3fl levels into quartiles, recipients with lower day one FOXP3fl had the highest rate of declining eGFR (p = 0.04). Thus, we concluded that low FOXP3fl splice variant levels at the first postoperative day in KTRs were associated with severe decline of eGFR.Paper IIWe hypothesized that low FOXP3 splice variant levels may reflect impairment of T regulatory cell function, which may affect T regulatory cell modulation of the inflammatory response to stimuli. Therefore, we examined the association between FOXP3 splice variant levels in peripheral blood of KTRs and primary outcome of prolonged inflammatory response (days in which C reactive protein (CRP) is above 50 mg/L), and the secondary outcome of severity of inflammatory response (maximal level of CRP elevation during period). FOXP3 splice variantswere measured day one post-transplant and day 29 days post-transplant. Day one FOXP3 splice variant levels were tested for association with outcome variables determined within the first period (within second day to 29 days posttransplant), and day 29 FOXP3 splice variant levels were tested for association with outcome variables determined within the second period (30th to the 57th day post-transplant). Of 507 KTRs included in the final analysis, 382 recipients had at least one CRP measurement &gt;50 mg/L in the first period and 69 recipients had at least one CRP measurement &gt;50 mg/L in the second period. We tested the association between FOXP3 splice variants and the primary outcome using negative binomial regression analysis, correcting for confounding factors. In the first period, we found a significant association between lower levels of Total FOXP3 and prolonged duration of CRP elevation, incidence rate ratio 0.61 (95% confidence interval 0.46-0.80), p&lt;0.01. Thus, we concluded that lower levels of Total FOXP3 mRNA levels in peripheral blood of kidney transplant recipients are associated with prolonged duration of inflammatory responses.Paper IIIThe aim of this paper was to explore if immunosuppressive medicines affect FOXP3 splice variant levels differently in female and male KTRs. This is of relevance because the function of the immune system may differ by biological sex as is evident by the higher risk of autoimmunity in females, and the higher risk of graft loss in younger female KTRs. Furthermore, recent publications reported conflicted results on the association of biological sex and FOXP3 expression levels. Therefore, we conducted a sex-based descriptive analysis of FOXP3 splice variant expression in female and male KTRs, as well as a sexbased descriptive analysis of FOXP3 splice variant in two healthy populations. We found that normalized FOXP3 splice variant levels were similar in 248 KTRs, pre-transplant, one day post-transplant and 29 days post-transplant. We also found similar levels of normalized FOXP3 levels in 101 healthy kidney donors. We confirmed the results of the healthy kidney donor cohort in a publicly available cohort of 33 healthy individuals (GSE97475). Thus, we conclude that normalized levels of FOXP3 splice variants are similar in healthy males and females and in KTRs despite the effects of immunosuppressive medicines.In conclusion, the results of this PhD dissertation suggest that peripheral blood levels of FOXP3 mRNA may provide insight into immunotolerance of KTRs to transplanted kidney allografts, and immune modulation of inflammatory responses in KTRs. This insight may suggest a potential of FOXP3 expression levels as indicators of the effects of immunosuppressive medicines on T regulatory cell function in KTRs, which the results show to be similar in female and male KTRs.</div

Historical Wood: Structure, Properties and Conservation

This book is a selection of manuscripts devoted to the conservation and preservation of wooden cultural heritage. The articles present the new methods for conservation of various historical wooden artefacts, reliable modern techniques for characterisation of the wood structure, properties and degree of degradation, and discusses problems and doubts related to all aspects of conservation and re-conservation of wooden cultural heritage. It contains both review and research papers to give the readers a broader picture of the problems and issues related to the conservation of wooden historical objects and structures. We need to remember that wooden cultural heritage is an integral part of our culture and history that define our humanity. We are obliged to protect it, save it from oblivion, and preserve it for future generations

Peripheral and central mechanisms in chronic human inflammatory and neuropathic pain and associated animal models

Imperial Users onl

Soybean

Soybean is an agricultural crop of tremendous economic importance. Soybean and food items derived from it form dietary components of numerous people, especially those living in the Orient. The health benefits of soybean have attracted the attention of nutritionists as well as common people

Effects of resveratrol and quercetin metabolites in adipogenesis and triglyceride metabolism of 3T3-L1 adipocytes and comparison to those of the parent compounds

305 p.El Resveratrol y la Quercetina son dos ingredientes funcionales a los que se les ha atribuido efecto reductor de grasa en diversos experimentos in vivo e in vitro. Sin embargo, su rápido metabolismo hace que solo una pequeña cantidad de estos compuestos lleguen al plasma y a los tejidos. Por esta razón, determinar si los metabolitos que derivan de estos compuestos fenólicos poseen o no actividad reductora de grasa es de gran interés. La presente tesis muestra por un lado, los resultados obtenidos tras el tratamiento con los principales metabolitos del resveratrol en pre-adipocitos en maduración y en adipocitos maduros 3T3-L1 y el análisis de sus posibles mecanismos de acción. Por otro lado, se analiza el potencial efecto de los metabolitos de la quercetina en el mismo tipo de células y las vías por las que ejercen esa función. Los resultados obtenidos demuestran que todos los metabolitos analizados del resveratrol contribuyen, en la misma medida que el polifenol, a la inhibición de la adipogenesis. En adipocitos maduros, aunque resultan activos, el resveratrol es mucho más eficaz. En el caso de la quercetina, solo se le puede atribuir este efecto al metabolito sulfatado y en adipocitos maduros únicamente. Ninguno de los metabolitos de la quercetina resulta eficaz en la inhibición de la adipogenesis. Por lo tanto, se puede concluir que el metabolismo de estos dos compuestos puede suponer una limitación en el caso de adipocitos maduros tratados con resveratrol y pre-adipocitos en maduración tratados con quercetina

Effects of resveratrol and quercetin metabolites in adipogenesis and triglyceride metabolism of 3T3-L1 adipocytes and comparison to those of the parent compounds

305 p.El Resveratrol y la Quercetina son dos ingredientes funcionales a los que se les ha atribuido efecto reductor de grasa en diversos experimentos in vivo e in vitro. Sin embargo, su rápido metabolismo hace que solo una pequeña cantidad de estos compuestos lleguen al plasma y a los tejidos. Por esta razón, determinar si los metabolitos que derivan de estos compuestos fenólicos poseen o no actividad reductora de grasa es de gran interés. La presente tesis muestra por un lado, los resultados obtenidos tras el tratamiento con los principales metabolitos del resveratrol en pre-adipocitos en maduración y en adipocitos maduros 3T3-L1 y el análisis de sus posibles mecanismos de acción. Por otro lado, se analiza el potencial efecto de los metabolitos de la quercetina en el mismo tipo de células y las vías por las que ejercen esa función. Los resultados obtenidos demuestran que todos los metabolitos analizados del resveratrol contribuyen, en la misma medida que el polifenol, a la inhibición de la adipogenesis. En adipocitos maduros, aunque resultan activos, el resveratrol es mucho más eficaz. En el caso de la quercetina, solo se le puede atribuir este efecto al metabolito sulfatado y en adipocitos maduros únicamente. Ninguno de los metabolitos de la quercetina resulta eficaz en la inhibición de la adipogenesis. Por lo tanto, se puede concluir que el metabolismo de estos dos compuestos puede suponer una limitación en el caso de adipocitos maduros tratados con resveratrol y pre-adipocitos en maduración tratados con quercetina

International radiobiology archives of long-term animal studies. I. Descriptions of participating institutions and studies

This document describes archived radiobiology animal studies. Information is presented on experimental details, pathology, radioactivity, results, dosimetry, status, and animal type employed