Borrelia burgdorferi evades the effects of ceftriaxone treatment in a mouse model of Lyme borreliosis

Borrelia burgdorferi infektoitujen hiirten antibioottihoidon jälkeinen oireilu Lymen borrelioosi on puutiaisten välittämä monimuotoinen infektiotauti, jonka tunnetuin oire on ns. vaeltava ihottuma eli erythema migrans. Muita tavallisia ilmentymiä ovat erityisesti nivel- ja hermosto-oireet sekä harvemmin sydän- ja silmäoireet. Suurin osa potilaista paranee täysin terveeksi antibioottihoidon avulla, mutta jopa 10 % borrelioosiin sairastuneista oireilee suositusten mukaisesta hoidosta huolimatta. Pitkittyneen oireilun on ajateltu johtuvan mm. infektion laukaisemasta autoimmuunitaudista tai kroonisesta infektiosta, mutta teorioiden tueksi ei ole kyetty esittämään kiistattomia todisteita. Onkin todennäköistä, että antibioottihoidon jälkeisen oireilun takana on useampia mekanismeja eikä yksi teoria selitä kaikkien potilaiden oireilua. Tässä väitöskirjatyössä on tutkittu hoidonjälkeistä borrelioosia hiirimallin avulla. Varhaisvaiheessa (2 viikkoa infektoinnin jälkeen) annettu antibiootti vähensi hiirten nivelturvotusta ja esti B. burgdorferi – bakteerin kasvun kudoksista otetuista näytteissä. Hoidettu¬jen hiirten B. burgdorferi -spesifiset IgG-luokan vasta-aineet pysyivät kuitenkin koholla ja osasta kudosnäytteistä löytyi B. burgdorferi:n DNA:ta PCR-tutkimuksen avulla. Mikäli hiiret hoidettiin myöhäisessä vaiheessa (yli 18 viikkoa infektoinnista) tulokset olivat muuten samanlaiset, mutta keftriaksoni ei vaikuttanut nivelturvotukseen. Näin hiirissä oli aikaansaatu tilanne, joka on hyvin samankaltainen ihmisen hoitoresistentin borrelia-artriitin kanssa: oireet jatkuvat, mutta taudinaiheuttajaa ei saada esiin. Inflammaatiota vaimentavaa anti-TNF-alphaa on käytetty nivelreuman hoidossa menestyksekkäästi huonosti muuhun hoitoon reagoivilla potilailla ja siitä syystä sen ajateltiin voivan vaikuttaa suotuisasti myös B. burgdorferi -infektoitujen hiirten hoidonjälkeiseen nivelturvotukseen. Sillä ei kuitenkaan ollut vaikutusta nivelturvotukseen, mutta yllättäen hoidon jälkeen osa hiirten kudosnäytteistä osoittautui viljelypositiivisiksi. On siis ilmeistä, että hiirimallissamme osa B. burgdorferi spirokeetoista pystyy välttämään keftriaksonihoidon vaikutuksen joko hakeutumalla elimistössä kudokseen, jossa antibiootin pitoisuus ei nouse riittävän korkeaksi, tai ne kykenevät muuntautumaan metabolisesti inaktiiviin tilaan eikä mikrobilääke yhdessä immuunipuolustuksen kanssa onnistu tappamaan niitä. Jatkotutkimuksissa selvitimme B. burgdorferi - spirokeetan mahdollista piilopaikkaa tutkimalla antibioottihoidon jälkeen useita eri kudoksia PCR-menetelmällä. Tulosten perusteella spirokeetta näyttää suosivan nivelkudosta tai soluja, joita esiintyy nivelessä runsaasti. On kuitenkin edelleen epäselvää, missä muodossa B. burgdorferi –spirokeetat säilyvät kudoksessa antibioottihoidon jälkeen.

Systemic lupus erythematosus in the elderly: Clinical and immunological characteristics.

Systemic lupus erythematosus (SLE) predominantly affects young women in their 20s. In 40 out of 250 (16%) patients with SLE seen in our hospital disease onset occurred after the age of 50. The interval between the time of onset and diagnosis was five years in this older group compared with three years in the younger group. Arthritis, as a first symptom, was less common in the older onset group. During the follow up a lower incidence of arthritis, malar rash, photosensitivity, and nephropathy was found in the older onset group. In contrast, this group showed an increased incidence of myositis. High titres of anti-dsDNA tended to occur less often and the incidence of anti-Ro antibodies was lower in the older onset group. These features seem to distinguish patients with older onset SLE as a particular subset.

Systemic lupus erythematosus in men: clinical and immunological characteristics.

Although systemic lupus erythematosus (SLE) has traditionally been considered a disease of women, men may also be affected. Thirty of 261 patients (12%) with SLE seen in this hospital were men. Arthritis was less common as a first symptom in the men, although this group of patients had discoid lesions and serositis more often than the women. During the follow up a lower incidence of arthritis and malar rash and a higher incidence of other skin complications including discoid lesions and subcutaneous lupus erythematosus was found in the men. The incidence of nephropathy, neurological disease, thrombocytopenia, vasculitis, and serositis, was similar in the two groups. No significant immunological differences were found between men and women. These features indicate that several gender associated clinical differences may be present in patients with SLE.

Avaliação dos efeitos colaterais da nevirapina em gestantes HIV positivo em Hospital Universitário do sul do Brasil

OBJETIVO: avaliar a freqüência de efeitos advesos com o uso da nevirapina e suas correlações em gestantes infectadas pelo vírus da imunodeficiência humana (HIV). MÉTODOS: estudo retrospectivo foi realizado entre janeiro de 2003 e dezembro de 2006, incluindo todas as mulheres que utilizaram nevirapina durante a gestação. Os critérios de exclusão foram: início da nevirapina antes da gestação; presença de enzimas hepáticas basais aumentadas e dados incompletos de bioquímica hepática no prontuário. Os parâmetros avaliados foram idade, duração de exposição à nevirapina, idade gestacional no início da medicação, semanas de seguimento, carga viral, contagem de CD4 e dosagens de transaminases. A incidência de efeitos adversos hepáticos e/ou cutâneos foi determinada e correlacionada com a contagem de CD4. As análises estatísticas foram realizadas utilizando o teste exato de Fisher e o teste t de Student quando apropriado. A significância estatística foi estabelecida quando p<"0,05. RESULTADOS: cento e cinqüenta e sete gestantes foram incluídas nos critérios estabelecidos. Trinta e uma mulheres (19,7%) apresentaram toxicidade cutânea e/ou hepática. Rash cutâneo foi responsável por 77,4% das toxicidades e anormalidade da função hepática por 22,6%. Hepatotoxicidades graus 1, 2 e 3 foram observadas em 0,6, 2,5 e 1,3%, respectivamente. Contagem de CD4, carga viral e dosagem de transaminases basais foram similares em gestantes com e sem reação induzida pela nevirapina. A contagem de CD4 média foi de 465,4 e 416,6 células/µL em mulheres com e sem efeitos colaterais, respectivamente (p=0,3). Todas as pacientes que apresentaram hepatotoxicidade apresentavam contagem de CD4 prévia ao tratamento superior a 250 células/µL. CONCLUSÕES: a incidência de eventos adversos com nevirapina em nosso estudo foi alta, mas a maioria deles foi cutâneo. Não houve correlação entre a alta contagem de CD4 e os eventos adversos quando se analisou conjuntamente as reações cutâneas e hepáticas; entretanto, a hepatotoxicidade ocorreu apenas em gestantes com contagem de CD4 > 250 células/µL.

ABCB1 C1236T, G2677T/A and C3435T polymorphisms in systemic lupus erythematosus patients

P-glycoprotein (Pgp), the ABCB1 gene product, acts as an efflux pump that transports a large variety of substrates and is a mechanism of cell protection against xenobiotics. An increasing number of studies have shown that some ABCB1 polymorphisms may affect Pgp expression and activity, as well as affecting the development and susceptibility to diseases and pharmacological response. High activity of Pgp has been detected in systemic lupus erythematosus (SLE) patients. The C1236T, G2677T/A, and C3435T are the most commonly studied single nucleotide polymorphisms in the ABCB1 gene. Therefore, their frequencies were determined in Brazilian individuals with European ancestry (N = 143) and in SLE patients (N = 137). Genotyping was performed by PCR-RFLP analysis using specific primers followed by incubation with the appropriate restriction enzymes. The resulting DNA fragments were visualized on agarose or polyacrylamide gels. No statistically significant differences were observed in allelic and genotypic frequencies between SLE and healthy subjects (Fisher exact test). Nevertheless, the 2677A allelic frequency was lower in SLE patients with malar rash (0.007) compared with patients without this feature (0.04; P = 0.0054), while the frequency of this variant was higher in SLE patients with pleuritis (0.07) compared with patients without this feature (0.01; P = 0.0156). We suggest that although the ABCB1 polymorphisms do not directly interfere in SLE susceptibility, their evaluation, especially the 2677A allele, in other immunological processes may be interesting since they can interfere in clinical features of this disease.

Merrimack Intelligencer Vol. 5 No. 48

This was a weekly paper that was published every Saturday. The motto of the Merrimack was: "Not too rash--Yet not fearful--We aim to be just." It was published from 1808-1817. Topics of interest include: Page 1: State of New York Republicans published a statement arguing against the war and the policies of John Adams and James Madison; account of the capture of York by the Americans, 27 April 1813; Page 2: account of the capture of York by the Americans, 27 April 1813; letter from American Brig. Gen. Henry Miller to Sir John B. Warren warning the British not to execute captured U.S. citizen O'Neal; response from Sir John B. Warren to Brig. Gen. Henry Miller stating that O'Neal had been released; account of Stephen Girard buying back his ransomed ship from the British; Page 3: account of Stephen Girard buying back his ransomed ship from the British; U.S. General Harrison repels British and Indian forces that attack Fort Meigs; account of British forces capturing U.S. privateer ship Alexander; report of British forces near Newport, New York, the Delaware river, and the Potomac River; report of Indian attacks in Kaskaskia, Randolph County; report of a boat load of provisions attacked by Indians near Fort Harrison; Commodore Isaac Chauncey arrived at Sacket's Harbor to unload stores taken from York before leaving for Niagara to commence attack against Fort George; U.S. Army announcement recruiting men 18 to 45 years of age to enlist in the army;

Setilement of motor accidents claims with special reference to Kerala

The accident toll on our road traffic is staggering. Obviously this appalling toll of life and.health represents heavy economic loss in addition to human tragedy. the enormous increase in the number of motor vehicles with its rash, negligent and reckless use by unscrupulous, inexperienced and dangerous drivers in the most miserably managed roads coupled with concomitant hazards would draw our attention that Accident Prevention, and Accident compensation are thoroughly two compatiable aims. Proposed solutions to the traffic Problems abound. Preventive efforts concentrated on each of the variables the driver, the road and the vehicle are all being initiated. Still it is a Will the .Motor Vehicles are not considered as dangerous machines. Motoring activity is found useful.A competent and specially trained police force has to be created to deal with the traffic offences in a more scientific ways.The term ‘legal representative needs to be defined on the constructive aspects of relation and dependence.Services of legal aid and public counsels shall necessarily be extended to the poor Motor Accident victims.Timely reporting and timely investigation of Motor Accidents cases will reduce the number of fraudulent claims. There are instances where cases are taken in to investigation after several months of occurrence.It is hoped that the suggestions made above as a result of the present study, if pwgninto practice, may make a humble contribution to the prevention sssof motor accidents and to a faster and speedier settlement of motor accident compensation claims.

Adaptación del Test de Diagnóstico Aritmético Keymath a la población escolar andaluza : primera fase.

Adaptación total del Test Keymath a las características educativas, lingüísticas y sociales de la población escolar andaluza siguiendo los procedimientos propuestos por Rash y Wright. 64 alumnos de segundo a séptimo de EGB del Colegio Cristo de la Yedra de Valor, Granada. Administración definitiva de la prueba a 278 alumnos de segundo curso de EGB, 142 niños y 136 niñas, del Colegio Caja de Ahorros, Colegio de Prácticas Masculino, Colegio Compañía de María, Colegio Público Fuente Nueva, Colegio Público San Matías, Colegio Público Inmaculada del Triunfo. Todos de Granada capital. De Granada provincia en el Colegio Público Sánchez Velayos de Ugijar. La prueba se realiza de marzo a junio del curso 1984-1985. Aplicación del test Keymath dividido en 14 subtests de forma individual, tomando como variables: habilidad aritmética demostrada y el dominio o no de determinadas destrezas. Edad, nivel de estudios, sexo, nivel socioecónomico, personalidad. Tests. La estimación de los parámetros de los elementos, se realiza siguiendo el procedimiento de estimación Ucon, utilizando la adaptación a Fortran 77 del Programa Bical realizado por Pérez Meléndez. Análisis de ajuste, utilizando un estadístico Chi cuadrado. Se observa la dificultad obtenida para los diferentes elementos sometidos a análisis. El orden de dificultad obtenido, en general, no presenta grandes variaciones con respecto al orden establecido en la prueba original americana. Los subtests geometría, medida y tiempo son los que ofrecen mayores cambios respecto al orden inicial. En los restantes subtests, el orden de dificultad obtenido es similar al de la prueba original. El Test Keymath es un instrumento útil para el diagnóstico de la habilidad matemática. El contenido de los elementos de Keymath, abarca todos los bloques temáticos incluidos en los programas renovados españoles para el Ciclo Inicial de EGB. A diferencia de los restantes tests de Matemáticas, hace mínimos los requisitos de lectura y escritura. Los resultados obtenidos en la prueba coinciden con las expectativas que los profesores tienen sobre sus alumnos.

Genotipificación de HLA-B en pacientes colombianos afectados por el síndrome Stevens-Johnson y la Necrólisis Epidérmica Tóxica

Las reacciones alérgicas a medicamentos cutáneas severas (RAM) como el Síndrome Stevens Johnson (SJS) y la Necrólisis Epidérmica Tóxica (NET),caracterizadas por exantema, erosión de la piel y las membranas mucosas, flictenas, desprendimiento de la piel secundario a la muerte de queratinocitos y compromiso ocular. Son infrecuentes en la población pero con elevada morbi-mortalidad, se presentan luego de la administración de diferentes fármacos. En Asia se ha asociado el alelo HLA-B*15:02 como marcador genético para SJS. En Colombia no hay datos de la incidencia de estas RAM, ni de la relación con medicamentos específicos o potenciales y tampoco estudios de aproximación genómica de genes de susceptibilidad.

Implementación del modelo estratégico de gestión para fundación cultural luna lunar, teatro corporal

El proyecto, propone implementar un modelo estratégico de gestión a corto, mediano y largo plazo que haga de la Fundación Cultural Luna Lunar, una industria cultural sostenible y rentable.

Diseño de escalas para la evaluación de la habilidad motriz de salto para la educación física en educación primaria.

Resumen del autor

Effect of viral load on the outcome of herpes zoster

Varicella-zoster virus (VZV) is a member of the Herpesviridae family, primary infection with which causes varicella, more commonly known as chicken pox. Characteristic of members of the alphaherpesvirus subfamily, VZV is neurotropic and establishes latency in sensory neurons. Reactivation of VZV causes herpes zoster, also known as shingles. The most frequent complication following zoster is chronic and often debilitating pain called postherpetic neuralgia (PHN), which can last for months after the disappearance of a rash. During episodes of acute zoster, VZV viremia occurs in some, but not all, patients; however, the effect of the viral load on the disease outcome is not known. Here we describe the development of a highly specific, sensitive, and reproducible real-time PCR assay to investigate the factors that may contribute to the presence and levels of baseline viremia in patients with zoster and to determine the relationship between viremia and the development and persistence of PHN. VZV DNA was detected in the peripheral blood mononuclear cells (PBMCs) of 78% of patients with acute zoster and in 9% of healthy asymptomatic blood donors. The presence of VZV in the PBMCs of patients with acute zoster was independently associated with age and being on antivirals but not with gender, immune status, extent of rash, the age of the rash at the time of blood sampling, having a history of prodromal pain, or the extent of acute pain. Prodromal pain was significantly associated with higher baseline viral loads. Viral load levels were not associated with the development or persistence of PHN at 6, 12, or 26 weeks.