Introdução: A luz intensa pulsada(LIP) tem sido muito utilizada no tratamento do fotoenvelhecimento sem completo conhecimento de seu mecanismo de ação. Métodos: Foram acompanhados 26 pacientes apresentando fotoenvelhecimento grau II-III (GLOGAU, 1994), os quais foram submetidas à avaliação clínica , histológica e imunoistoquímica 6 e 12 meses após o término do tratamento com LIP. Foram realizadas cinco sessões com intervalos de trinta dias. Além da quantificação histomorfométrica das fibras colágenas e elásticas na derme, foram avaliados CD1, CD4, CD8 e ICAM-1. Resultados: Após 6 meses houve melhora clínica moderada e intensa em 76,92% dos casos e a nota média de satisfação foi 8,57 correspondendo à melhora moderada. Após 12 meses do término do tratamento observou-se que 51,52% das pacientes apresentaram uma melhora clínica moderada em relação à clínica inicial. Os efeitos colaterais foram eritema (11/26), edema (10/26), ardência (7/26) e crostas (8/26). A quantificação das fibras colágenas mostrou aumento médio de 51,33% proporção média de fibra colágena na derme após 6 meses de tratamento e o aumento em relação a 12 meses do término do tratamento foi 30,17%; as fibras elásticas mostraram aumento de 44,13% após 6 meses e aumento de 143,19% após 12 meses do término do tratamento. Na análise imunoistoquímica não houve alteração de CD1 e CD8. Em relação ao CD4 houve redução significante após 12 meses do término do tratamento. Quanto ao ICAM-1 houve aumento em 6 meses com retorno aos níveis normais após 12 meses do término do tratamento. Conclusão: A melhora clínica observada foi comprovada pelo estudo histopatológico, que mostrou aumento das fibras colágenas e elásticas na derme. Após 12 meses do término do tratamento observou-se discreta redução do aspecto clínico da pele correlacionado ao histopatológico. Poucos efeitos colaterais foram observados, sendo todos reversíveis. Desta forma, a LIP constitui boa opção de tratamento para o fotoenvelhecimento cutâneo, sendo uma técnica não ablativa, segura e eficaz. / Introduction: The intense pulsed light has been used in the treatment of photoaging without full knowledge of its mechanism of action. Material and Methods: 26 patients were followed-up presenting photoaging grade II-III (GLOGAU, 1994), who were submitted to clinical evaluation, histological and immunohistochemistry 6 and 12 months after the treatment termination with LIP. Five sessions were made with 30-day intervals. In addition to histomorphometric quantification of collagen and elastic fibers in the dermis, CD1, CD4, CD8 and ICAM-1 were evaluated. Results: After 6 months there were moderate and intense clinical improvement on 76.92% of the cases and the mean score of satisfaction was 8.57 corresponding to moderate improvement. After 12 months of the treatment termination, it was observed that 51.52% of the patients presented a moderate clinical improvement in relation to initial clinic. The side effects were erythema (11/26), edema (10/26), burning (7/26) and crusts (8/26). The quantification of collagen fibers has shown mean increase of 51.33% in the dermis after 6 months of treatment and the increase regarding to 12 months of the treatment termination was of 30.17%; the elastic fibers has shown an increase of 44.13% after 6 months and increase of 143.19% after 12 months of the treatment termination. In the immunohistochemistry analysis there was no alteration of CD1 and CD8. In relation to CD4, there was a significant reduction after 12 months of treatment termination. Regarding the ICAM-1, there was an increase in 6 months with return to normal levels after 12 months of treatment termination. Conclusion: The observed clinical improvement was verified by the histopathologic study, which showed increase in the elastic and collagen fibers in the dermis. After 12 months of treatment termination, it was observed a discrete reduction of clinical aspect of skin correlated to histopathology. A few side effects were observed, being all reversible. Thus, LIP constitutes good option of treatment for skin photoageing, being a non-ablative, safe and effective technique.

A síndrome metabólica (SM) é uma condição clínica que agrupa uma variedade de morbidades, como hiperglicemia, pressão arterial elevada, dislipidemia aterogênica e obesidade (particularmente na região abdominal). Nessa conjuntura, os principais tecidos-alvo da ação da insulina sofrem alterações metabólicas que aumentam o risco de ocorrência de doenças cardiovasculares e diabetes tipo 2. As alterações teciduais observadas são caracterizadas por infiltrados de células do sistema imune, especialmente macrófagos. Citocinas pró-inflamatórias, como TNF-α, são liberadas e alcançam a corrente sanguínea, promovendo nesses indivíduos um estado de inflamação crônica e sistêmica. O tecido adiposo intra-abdominal parece ser de particular importância no estabelecimento desse quadro inflamatório, e estratégias direcionadas no sentido de modular os processos inflamatórios nesse tecido podem atenuar as consequências da SM. Os reconhecidos benefícios da terapia com luz de baixa potência em condições inflamatórias nos permitem supor que essa poderia ser uma proposta terapêutica para a SM. Sendo esse o nosso foco de estudo, camundongos adultos, machos, das linhagens C57BL/6 e BALB/c receberam dieta hiperlipídica durante 8 semanas para indução do quadro de SM. Os animais foram então irradiados sobre a superfície abdominal no decorrer de 21 dias, usando um LED (λ = 850 nm, 6 sessões, 300 s por sessão, potência = 60 mW, fluência = 6 J/cm², taxa de fluência = 19 mW/cm²). Antes e durante o tratamento, amostras de sague foram coletadas para quantificação de glicose, colesterol total e triglicérides plasmáticos. Considerando os parâmetros de irradiação adotados, a terapia com luz de baixa potência não se mostrou efetiva para alterar massa corporal, glicemia, colesterol total e triglicérides de camundongos alimentados com dieta hiperlipídica. / Metabolic syndrome comprises a constellation of morbidities such as insulin resistance, hyperinsulinemia, atherogenic dyslipidemia, dysglycemia and obesity (especially abdominal). Metabolic alterations are observed in major insulin target organs, increasing the risk of cardiovascular diseases, type-2 diabetes and therefore mortality. Tissue alterations are characterized by immune cells infiltrates (especially activated macrophages). Released inflammatory mediators such as TNF-α induce chronic inflammation in subjects with metabolic syndrome, since inflammatory pathways are activated in the neighboring cells. The intra-abdominal adipose tissue appears to be of particular importance in the onset of the inflammatory state, and strategies contributing to modulate the inflammatory process within this adipose tissue can mitigate the metabolic syndrome consequences. Considering the low level light therapy (LLLT) recognized benefits in inflammatory conditions, we hypothesized this therapeutic approach could promote positive effects in modulating the inflammatory state of metabolic syndrome. That being the scope of this study, male C57BL/6 AND BALB/c mice were submitted to a high-fat/high-fructose diet among 8 weeks to induce metabolic syndrome. Animals were then irradiated on the abdominal region during 21 days using an 850 nm LED (6 sessions, 300 seconds per session, 60 mW output power, ~6 J/cm² fluence, ~19 mW/cm² fluence rate). Before and during treatment, blood was sampled either from the retro-orbital plexus or from tail puncture for glucose, total cholesterol and triglycerides analysis. Our results indicate no alterations on these metabolic parameters after LLLT.

Alguns ramos da Medicina vêm empregando lasers ou LEDs de baixa potência em diversas especialidades. Estes lasers e LEDs são classificados como luz de baixa potência (LBP) e são usados na área de Fototerapia com comprimentos de onda na faixa do vermelho e do infravermelho. Por outro lado, a área de dosimetria utiliza dispositivos (dosímetros) capazes de estimar a energia depositada devido a exposição prévia à radiação ionizante usando luz visível como estímulo para obtenção de um sinal luminoso - esta técnica é a luminescência opticamente estimulada (OSL). O objetivo deste trabalho é avaliar a possibilidade de estimar a energia entregue por iluminação com laser e LED de baixas potências com comprimentos de onda na faixa do vermelho e infravermelho, utilizados na Fototerapia, empregando a dosimetria OSL. Foram empregados dosímetros de óxido de alumínio, óxido de berílio e fluorita natural, irradiados previamente com radiação beta (dose absorvida de aproximadamente 50 mGy), e iluminados com laser de 658 nm ou LED de 870 nm. Utilizamos o laser com potências de 10, 20, 50 e 100 mW, na faixa de energias de 0,1 a 13,2 J, e os LEDs com potências de 14,5, 58,0 e 130,5 mW, com faixa de energia entre 0,2 e 23,5 J. Para a medida de OSL foi utilizado o leitor TL/OSL Risø (modelo TL/OSL-DA-20) no modo de leitura CW-OSL e estimulo com LED de luz azul de 72 mW. A análise das curvas de emissão OSL foi feita observando tendências na modificação do sinal inicial OSL (integrado no primeiro 1s de leitura) e no sinal OSL total (integrado em 100 s) normalizados por sinal OSL obtido para irradiação padronizada. Os resultados obtidos mostraram que a iluminação com laser de 658 nm reduz o sinal OSL das amostras de óxido de alumínio para energias entre ~0,1 e ~12 J, e o sinal OSL de fluorita em uma faixa de energias mais baixa, entre ~0,1 e ~4 J. Para a iluminação com LED de 870 nm somente as amostras de fluorita mostraram redução do sinal OSL, no intervalo de ~0,1 e ~15 J de energia luminosa incidente; essa mudança foi mais acentuada para o sinal inicial da curva OSL do que para o sinal integrado. As mudanças observadas são independentes das potências luminosas empregadas. As amostras de óxido de berílio não mostraram mudanças na emissão OSL para nenhum dos feixes de luz no intervalo de energia utilizados. Além destes resultados também foi observado que a iluminação com diferentes energias luminosas incidentes nas amostras muda o formato das curvas de emissão OSL das amostras de fluorita: o tempo característico de decaimento das curvas de emissão cresce à medida que mais energia luminosa (infravermelho) é depositada nas amostras. Os resultados mostraram que a técnica OSL poderia ser utilizada para a avaliar de energia luminosa incidente no óxido de alumínio, iluminado com laser de 658 nm, e na fluorita natural, iluminada com LED de 870 nm. Para a fluorita, a mudança nas curvas de emissão OSL das amostras também pode estar relacionada com a energia luminosa incidente nela, fato que deverá ser mais bem estudado em trabalhos posteriores. / Some branches of Medicine are using low power lasers and LEDs in various specialties. These devices are classified as low-power or low-level lasers and LEDs and they are used in phototherapy in the red and infrared wavelength range. On the other hand, in dosimetry some devices (dosimeters) are used to estimate the deposited energy due to a previous exposure to ionizing radiation through a visible light stimulus to get a light signal - this technique is the optically stimulated luminescence (OSL). The objective of this study is to evaluate the possibility of assessing the energy delivered by illumination with laser and LED in the red and infrared wavelength ranges, used in the phototherapy, using the OSL technique. OSL dosimeters of aluminum oxide, beryllium oxide and natural fluorite were used. They were previously exposed to beta radiation (absorbed dose of about 50 mGy) and illuminated with 658 nm laser or 870 nm LED. The laser powers were 10, 20, 50 and 100 mW, and the light energy was in the range 0.1 to 13.2 J; and the chosen LED powers were 14.5, 58.0, 130.5 mW, delivering energies in the range 0.2 to 23.5 J. The OSL emission curves were measured with the TL/OSL Risø (TL/OSL-DA-20 model), CW-OSL mode, stimulating light provided by blue LEDs of 72 mW. The analysis of the OSL curves was carried out through the observation of trends in the variations of initial OSL signal (integrated in the first 1 s) and the whole OSL signal (integrated in 100 s) normalized by an OSL signal due to a standard irradiation. The results showed that the illumination with 658 nm laser reduces the OSL signal from aluminum oxide samples in the energy range between ~0.1 and ~12 J, and from fluorite in the energy range from ~0.1 to ~4 J. For the 870 nm LED illumination, only fluorite samples showed a reduction in the OSL signal in the range from ~ 0.1 to ~ 15 J of incident light energy. This change was more pronounced for the initial OSL signal than for the integrated signal. The observed changes were independent of the light power used in the illumination. The OSL signal of beryllium oxide samples showed no changes for any of the light beams used. It was also observed that illumination with different incident light energy changes the shape of fluorite OSL curves. The characteristic decay time of the emission curves grows as the light energy (infrared) deposited on the samples of fluorite increases. The results showed that the OSL technique could be used to evaluate the light energy incident on aluminum oxide, illuminated with 658 nm laser, and on fluorite, illuminated with 870 nm LED. For fluorite samples, the change in the OSL emission curve can also be related to the incident light energy. This fact needs further studies for a better understanding.

Purpose: To explore the difference between continuous and pulsed photobiomodulation (PBMT) versus a placebo treatment when using a red-blue light combination over multiple treatment sessions to decrease the symptoms of muscle damage in the quadriceps muscle after a bout of muscle damaging exercise. Methods: Thirty-six healthy, nonactive male and female participants were randomly assigned to one of three groups: continuous PBMT, pulsed PBMT, and placebo treatment. Participants were assessed for muscle damage with knee extension maximal isometric and isokinetic contractions, as well as Visual Analog Scale (VAS) and Lower Extremity Functional Scale (LEFS) scores. Blood creatine kinase (CK) was also analyzed. Participants were given treatment immediately prior to undergoing a bout of damaging eccentric exercise. Participants were treated with PBMT for the next 4 consecutive days for a total of 5 treatments. Results: The continuous treatment group lost significantly less isokinetic average peak torque than the placebo treatment when averaged across all time points postexercise. However, for isometric testing, the continuous group had more reduction in force compared to the placebo group. Between the treatment groups, the continuous treatment group had significantly more muscle soreness measured by the VAS and had significantly less function in daily tasks reported on the LEFS patient-oriented outcome scale. There was no significant difference in level of creatine kinase between the treatment groups. Conclusion: Pulsed photobiomodulation treatments had no significant effect when compared to the placebo group. Continuous photobiomodulation helped to reduce isokinetic force loss, yet exacerbated all other muscle damage markers following exercise relative to the placebo condition.

This thesis consists of two major chapters, each with its own introduction, experimental section and discussion. The TG4T/daunomycin and G4/daunomycin complexes described in Chapter One are two out of only five crystallographic quadruplex/ligand structures reported to date. In both structures daunomycin molecules stack onto a terminal G quartet preventing the G4 quadruplex from destacking and unwinding. The number of interacting ligand molecules depends on the quadruplex structure itself. The G4 quadruplex can accommodate four daunomycin molecules within one layer, while the TG4T tetraplex only accommodates three. In both structures daunosamine moieties form hydrogen bonds with the quadruplex but only daunosamine moieties from the TG4T/daunomycin structure make slight incursions into the quadruplex grooves. Both structures are stabilised by π-π interactions, hydrogen bonds, Van der Waals contacts and electrostatic interactions. The daunomycin/TG4T complex is the first ever reported and the only structure where a ligand interacts directly with the quadruplex groove. Chapter Two describes nine crystal structures of Hoechst 33258 analogues with d(CGCAAATTTGCG)2 and d(CGCGAATTCGCG)2 oligonucleotides, and is divided into two sections. Section A includes seven structures with Halogenated Hoechst 33258 analogues that are potential agents in radiotherapy, phototherapy, radioimmunotherapy or photoimmunotherapy, and the structure of the precursor. In all of the examined complexes the ligand binds to the minor groove but not all halogen substituents refine to 100% occupancy. The refined occupancies of the halogen atoms reveal that the degree of carbon-halogen cleavage is highest for ortho and lowest for para substitution. Among meta substituents pointing outside the minor groove, bromine atoms had a higher occupancy than the larger iodines. The position of the halogen atom in the minor groove is influenced by additional substituents on the phenyl ring. In most cases the bulky halogen atom is facing outside of the minor groove. Only in the 3-iodo-5-isopropylHoechst complex is iodine positioned towards the floor of the groove allowing the big isopropyl group to face outside. Section B describes the structure of a carborane-containing ligand (JW-B) bound to the minor groove of d(CGCAAATTTGCG)2. The analysis shows that is possible to position boron-rich moieties close to the cell nucleus, and JW-B may have potential in Boron Neutron Capture Therapy. / Data file restricted at the request of the author, but available by individual request, use the feedback form to request access.

<p>Bilirubin is a degradation product of haem, which is constantly formed in all</p><p>mammals. Increased levels of bilirubin in humans lead to jaundice, a condition</p><p>that is very common during the first days after birth. This neonatal</p><p>jaundice can routinely be treated by phototherapy without any serious side</p><p>effects. During this treatment, bilirubin undergoes a photoreaction to isomers</p><p>that can be excreted. The most efficient photoreaction is the isomerisation</p><p>around a double bond (Z-E-isomerisation), which results in more soluble</p><p>photoproducts.</p><p>The work presented in this thesis shows results of a femtosecond optical</p><p>spectroscopy study, combined with quantum-mechanical investigations, of</p><p>the mechanism of isomerisation of bilirubin. The spectroscopic research was</p><p>conducted with bilirubin in organic solvents, and in buffer complexed by</p><p>human serum albumin. This albumin complex is present in the blood, and</p><p>has thus medical importance. Quantum-chemical calculations (CASSCF) on</p><p>a bilirubin model were used to explain experimental results.</p><p>The fluorescence decay observed with femtosecond spectroscopy shows an</p><p>ultrafast component (~120 fs), which is explained by exciton localisation,</p><p>followed by processes with a lifetime of about 1-3 ps. These are interpreted</p><p>as the formation of a twisted intermediate, which decays with a lifetime of</p><p>10-15 ps back to the ground state, as observed by absorption spectroscopy.</p><p>CASSCF calculations, in combination with the experimental results, suggest</p><p>the ca. 1-3 ps components to be relaxation to the twisted S1 minimum, followed</p><p>by the crossing of a barrier, from where further relaxation takes place</p><p>through a conical intersection back to the ground state.</p><p>Time-dependent DFT calculations were utilised to analyse the absorption</p><p>spectrum of bilirubin. Good agreement with the measured spectrum was</p><p>achieved, and low-lying states were observed, that need further investigation.</p><p>The theoretically obtained CD spectrum provides direct evidence that</p><p>bilirubin preferentially binds to human serum albumin in the enantiomeric</p><p>P-form at neutral pH.</p> / <p>Bilirubin är en nedbrytningsprodukt av hem som ständigt bildas hos alla</p><p>däggdjur. En förhöjd bilirubinkoncentration i den mänskliga kroppen kan</p><p>leda till gulsot, något som är mycket vanligt under de första dagarna efter</p><p>födelsen (neonatal gulsot). Fototerapi används rutinmässigt som säker behandlingsmetod,</p><p>under vilken bilirubin genomgår en fotoreaktion till en</p><p>isomer som kan utsöndras. Den mest effektiva fotoreaktionen är en Z-Eisomerisation,</p><p>vilken leder till lösligare fotoprodukter.</p><p>Arbetet som presenteras i denna avhandling visar resultaten av en kombinerad</p><p>femtosekund optisk-spektroskopisk och kvantmekanisk undersökning</p><p>av mekanismen bakom bilirubins isomerisation. Den spektroskopiska</p><p>studien genomfördes med bilirubin, löst i organiska lösningsmedel och i</p><p>buffert i komplex med humant serumalbumin. Detta albuminkomplex finns i</p><p>blodet, och är därför av medicinskt intresse. Kvantmekanistiska CASSCFberäkningar</p><p>på en bilirubinmodell användes för att förklara de experimentella</p><p>resultaten.</p><p>Det uppmätta fluorescence sönderfallet visar ultrasnabba komponenter</p><p>(~120 fs). Dessa tolkas som excitonlokalisering, som följs av bildandet av</p><p>ett vridet intermediat med en hastighetskonstant på ca. 1 ps-1(beroende på</p><p>lösningsmedlet). Absorptionsmätningar visar att detta intermediat sönderfaller</p><p>tillbaka till grundtillståndet med en livstid på 10-15 ps.</p><p>CASSCF beräkningar, i kombination med de experimentella resultaten, tyder</p><p>på att sönderfallet med livslängden på ca. 1 ps är en relaxation till det</p><p>vridna S1-tillståndet. Reaktionsvägen därifrån antas passera en barriär till en</p><p>konisk genomskärning, som möjliggör snabb relaxation till grundtillståndet.</p><p>Tidsberoende DFT-beräkningar användes för att analysera bilirubins absorptionsspektrum,</p><p>vilket gav bra överensstämmelse med uppmätta data. Dessutom</p><p>hittades ett tillstånd med låg excitationsenergi, som kräver ytterligare</p><p>studier. Med hjälp av det beräknade CD-spectret kunde det visas att bilirubin</p><p>binder till albumin i P-formen vid neutralt pH.</p>

<p>En stor del av personalen inom Hälso- och Sjukvården har sin arbetstid förlagd till natten. Vi vet idag att det är mycket ogynnsamt att arbeta nattetid och att det höjer risken att utveckla flera sjukdomar. Nattarbete och roterande skiftarbete stör och påverkar den naturliga dygnsrytmen i kroppen. Kan vi hjälpa kroppen att anpassa sig bättre till nattskiftsarbete med hjälp av ljusterapins effekter? Ljusterapi är, vad vi känner till idag, en säker behandling med få eller inga biverkningar. Den är lätt att administrera, relativt billigt och flexibel att utföra. Det optimala verkar vara, enligt vår nuvarande kunskap, att få ljusterapibehandling intermittent under nattpasset, kombinera detta med att använda sig av mörka solglasögon när man tar sig hem samt sedan att lägga sig att sova så snart som möjligt efter hemkomsten i ett mörkt rum. Ljusterapi hjälper speciellt inför längre perioder av nattpass men har också en mycket god effekt på att återställa den inre klockan till dag-dygnsrytm igen efter avslutad nattperiod. Ljusterapibehandling visar sig hjälpa även mot problem med ett förtidigt uppvaknande, som är ett vanligt fenomen vid nattarbete, och effekten av behandlingen kan kvarstå i upp till en månad. Den positiva höjningen av funktionsnivån som även inträffar kan också kvarstå så länge.</p>

Bilirubin is a degradation product of haem, which is constantly formed in all mammals. Increased levels of bilirubin in humans lead to jaundice, a condition that is very common during the first days after birth. This neonatal jaundice can routinely be treated by phototherapy without any serious side effects. During this treatment, bilirubin undergoes a photoreaction to isomers that can be excreted. The most efficient photoreaction is the isomerisation around a double bond (Z-E-isomerisation), which results in more soluble photoproducts. The work presented in this thesis shows results of a femtosecond optical spectroscopy study, combined with quantum-mechanical investigations, of the mechanism of isomerisation of bilirubin. The spectroscopic research was conducted with bilirubin in organic solvents, and in buffer complexed by human serum albumin. This albumin complex is present in the blood, and has thus medical importance. Quantum-chemical calculations (CASSCF) on a bilirubin model were used to explain experimental results. The fluorescence decay observed with femtosecond spectroscopy shows an ultrafast component (~120 fs), which is explained by exciton localisation, followed by processes with a lifetime of about 1-3 ps. These are interpreted as the formation of a twisted intermediate, which decays with a lifetime of 10-15 ps back to the ground state, as observed by absorption spectroscopy. CASSCF calculations, in combination with the experimental results, suggest the ca. 1-3 ps components to be relaxation to the twisted S1 minimum, followed by the crossing of a barrier, from where further relaxation takes place through a conical intersection back to the ground state. Time-dependent DFT calculations were utilised to analyse the absorption spectrum of bilirubin. Good agreement with the measured spectrum was achieved, and low-lying states were observed, that need further investigation. The theoretically obtained CD spectrum provides direct evidence that bilirubin preferentially binds to human serum albumin in the enantiomeric P-form at neutral pH. / Bilirubin är en nedbrytningsprodukt av hem som ständigt bildas hos alla däggdjur. En förhöjd bilirubinkoncentration i den mänskliga kroppen kan leda till gulsot, något som är mycket vanligt under de första dagarna efter födelsen (neonatal gulsot). Fototerapi används rutinmässigt som säker behandlingsmetod, under vilken bilirubin genomgår en fotoreaktion till en isomer som kan utsöndras. Den mest effektiva fotoreaktionen är en Z-Eisomerisation, vilken leder till lösligare fotoprodukter. Arbetet som presenteras i denna avhandling visar resultaten av en kombinerad femtosekund optisk-spektroskopisk och kvantmekanisk undersökning av mekanismen bakom bilirubins isomerisation. Den spektroskopiska studien genomfördes med bilirubin, löst i organiska lösningsmedel och i buffert i komplex med humant serumalbumin. Detta albuminkomplex finns i blodet, och är därför av medicinskt intresse. Kvantmekanistiska CASSCFberäkningar på en bilirubinmodell användes för att förklara de experimentella resultaten. Det uppmätta fluorescence sönderfallet visar ultrasnabba komponenter (~120 fs). Dessa tolkas som excitonlokalisering, som följs av bildandet av ett vridet intermediat med en hastighetskonstant på ca. 1 ps-1(beroende på lösningsmedlet). Absorptionsmätningar visar att detta intermediat sönderfaller tillbaka till grundtillståndet med en livstid på 10-15 ps. CASSCF beräkningar, i kombination med de experimentella resultaten, tyder på att sönderfallet med livslängden på ca. 1 ps är en relaxation till det vridna S1-tillståndet. Reaktionsvägen därifrån antas passera en barriär till en konisk genomskärning, som möjliggör snabb relaxation till grundtillståndet. Tidsberoende DFT-beräkningar användes för att analysera bilirubins absorptionsspektrum, vilket gav bra överensstämmelse med uppmätta data. Dessutom hittades ett tillstånd med låg excitationsenergi, som kräver ytterligare studier. Med hjälp av det beräknade CD-spectret kunde det visas att bilirubin binder till albumin i P-formen vid neutralt pH.

En stor del av personalen inom Hälso- och Sjukvården har sin arbetstid förlagd till natten. Vi vet idag att det är mycket ogynnsamt att arbeta nattetid och att det höjer risken att utveckla flera sjukdomar. Nattarbete och roterande skiftarbete stör och påverkar den naturliga dygnsrytmen i kroppen. Kan vi hjälpa kroppen att anpassa sig bättre till nattskiftsarbete med hjälp av ljusterapins effekter? Ljusterapi är, vad vi känner till idag, en säker behandling med få eller inga biverkningar. Den är lätt att administrera, relativt billigt och flexibel att utföra. Det optimala verkar vara, enligt vår nuvarande kunskap, att få ljusterapibehandling intermittent under nattpasset, kombinera detta med att använda sig av mörka solglasögon när man tar sig hem samt sedan att lägga sig att sova så snart som möjligt efter hemkomsten i ett mörkt rum. Ljusterapi hjälper speciellt inför längre perioder av nattpass men har också en mycket god effekt på att återställa den inre klockan till dag-dygnsrytm igen efter avslutad nattperiod. Ljusterapibehandling visar sig hjälpa även mot problem med ett förtidigt uppvaknande, som är ett vanligt fenomen vid nattarbete, och effekten av behandlingen kan kvarstå i upp till en månad. Den positiva höjningen av funktionsnivån som även inträffar kan också kvarstå så länge.

Eine Erhöhung des Bilirubins über 2 mg/dl betrifft 90 % aller Neugeborenen. Sie ist meist physiologisch und tritt optisch sichtbar bei 60-70 % dieses Kollektivs auf. In der pathologischen, exzessiv erhöhten Form ist sie der häufigste Grund für eine stationäre Wiederaufnahme während der ersten sieben Lebenstage. Ihre schwerste Komplikation, der Kernikterus, scheint - trotz allgemein verfügbarer, preiswerter und sicherer Therapiemöglichkeiten - wieder vermehrt aufzutreten. Die Gründe liegen im Überwachungsdefizit bei früher Entlassung von schlecht aufgeklärten Eltern, Nichtbeachtung der Besonderheiten der Neugeborenen ≤ 38 Schwangerschaftswochen und der zunehmenden Tendenz zum Stillen bei häufig unzureichender Anleitung. Ferner werden ikterische Kinder nur zu oft lediglich visuell bezüglich des Grades der Bilirubinämie eingeschätzt und die Therapie somit erheblich verzögert. Gegenstand dieser Arbeit ist die Frage, ob aus der Dynamik des Serumbilirubinspiegels von der Geburt bis zum 3. Lebenstag die Wahrscheinlichkeit des Auftretens einer phototherapiepflichtigen Hyperbilirubinämie abgeschätzt werden kann. Dazu wurde der Serumbilirubinspiegel direkt postnatal aus dem Nabelschnurblut, bzw. am 3. Lebenstag gleichzeitig mit dem Stoffwechselscreening ermittelt und der Phototherapiebedarf im Verlauf festgehalten. Um die Aussage zu präzisieren, wurde die Studienpopulation aus 2573 Kindern weiter unterteilt in 2180 reife tAGA- (hier Eu- und Hypertrophe), 267 reife tSGA-Kinder (Hypotrophe) und 126 FG (Frühgeborene). In allen 3 Gruppen korrelierten das Nabelschnurbilirubin und der Serumbilirubinwert vom 3. Lebenstag positiv mit der Entwicklung einer Hyperbilirubinämie. Anhand dieser Ausgangswerte konnten Grenzen für Hoch-, Mittelhoch-, Mittelniedrig- und Niedrigrisikogruppen definiert werden, welche die Entwicklung einer Hyperbilirubinämie mit einer Wahrscheinlichkeit von ≥ 20 %, 5-20 %, 0 < x <5 % und 0 % voraussagen. Damit kann man bereits früh eine Vorabselektion entsprechend dem Gefährdungspotential treffen und die Verlaufskontrollen entsprechend terminieren. Als Risikofaktoren einer therapiepflichtigen Hyperbilirubinämie wurden außerdem Frühgeburtlichkeit, seltener tSGA, geringes Geburtsgewicht und niedriges Gestationsalter (in der vorliegenden FG-Gruppe nicht signifikant) gefunden. Im Falle einer Sectiogeburt und bei Zuhilfenahme von Hilfsmitteln im Rahmen einer vaginalen Entbindung nahm der Bedarf an Phototherapie in der tAGA- und tSGA-Gruppe zu.