Effects of moxibustion on learning and memory ability and the hippocampal BDNF/TrkB expressions in the rats of vascular dementia / 中国针灸

OBJECTIVE@#To explore the effects of (resolving stasis, promoting collateral circulation) moxibustion on learning and memory ability and the expressions of brain derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) in the rats of vascular dementia (VD) in the microenvironment of neurovascular niche.@*METHODS@#Using 2-vessel occlusion (2-VO), the VD rat models were duplicated. The neural stem cells (NSCs) labeled with lentiviral vector-mediated enhanced green fluorescent protein (EGFP) were co-cultured with endothelial progenitor cells (EPCs) to structure the NSCs + EPCs implant. The implant was transplanted into the lateral ventricle of VD rats and the VD rat models with neurovascular niche were established. In No.1 experiment, the successful-modeled rats were divided into 3 groups, i.e. a NSCs + EPCs moxibustion group, a NSCs + EPCs blank group and a model group, 12 rats in each one. No any treatment was provided in the model group and the NSCs + EPCs blank group. The moxibustion therapy was adopted in the NSCs + EPCs moxibustion group, in which, the suspending moxibustion technique was applied to "Baihui" (GV 20), "Dazhui" (GV 14) and "Shenting" (GV 24), 20 min at each acupoint. The treatment was given once every day and a 14-day treatment was as one course. Totally, 3 courses of treatment were required. At the end of treatment, Morris water maze experiment was adopted to determine the learning and memory ability of the rats in each group. In the No.2 experiment, the model rats were divided into 3 groups, a NSCs + EPCs moxibustion group, a NSCs + EPCs blank group and a model group, 18 rats in each one. In each group, according to the durations of treatment, 3 subgroups were divided and 6 rats in each one. The intervention method was same as the No.1 experiment. Additionally, after corresponding treatment course, using perfusion, the brains were collected in each subgroup and the slices were frozen. BDNF/TrkB expressions were observed in the immunofluorescence test.@*RESULTS@#After treatment, in the NSCs + EPCs moxibustion group, the escape incubation was reduced, the time of the first running-cross platform was shortened and the frequency of running-cross platform increased as compared with the model group and the NSCs + EPCs blank group (<0.01, <0.05). The protein expressions were increased in tendency among the 3 courses of treatment in the NSCs + EPCs moxibustion group, indicating the significant differences (all <0.05), in which, the increase of the protein expressions in the NSCs + EPCs moxibustion group was better than the NSCs + EPCs blank group (<0.05, <0.01).@*CONCLUSION@#The moxibustion therapy is the effective approach to VD in clinical treatment. This therapy up-regulates the BDNF/TrkB protein expressions in the microenvironment of neurovascular niche, co-modulates NSCs-EPCs coupling mechanism, promotes nerve neogenesis and repairs the injured nerve.

DNA immunization of Mycobacterium tuberculosis resuscitation-promoting factor B elicits polyfunctional CD8+ T cell responses

PURPOSE: T cell-mediated immune responses, and particularly activation of polyfunctional T cells that simultaneously produce multiple cytokines, are necessary for the control of Mycobacterium tuberculosis. In the present study, we examined if DNA immunization of Mycobacterium tuberculosis resuscitation-promoting factor B (RpfB) elicits polyfunctional T cell responses in mice. MATERIALS AND METHODS: C57BL/6 mice were immunized intramuscularly three times, at 3-week intervals, with RpfB-expressing plasmid DNA. For comparison, protein immunization was performed with recombinant RpfB in control mice. After immunization, RpfB-specific T cell responses were assessed by interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot assay and intracellular cytokine staining (ICS), and T cell polyfunctionality was assessed from the ICS data. RESULTS: RpfB DNA immunization induced not only humoral immune responses, but also CD8+ and CD4+ T cell responses. Immunodominant T-cell epitopes were identified within RpfB by assays with overlapping peptides. RpfB DNA immunization elicited a polyfunctional CD8+ T cell response that was dominated by a functional phenotype of IFN-gamma+/TNF-alpha+/IL-2-/CD107a+. CONCLUSION: RpfB DNA immunization elicits polyfunctional CD8+ T cell responses, suggesting that RpfB DNA immunization might induce protective immunity against tuberculosis.

Trends in Scientific Literature on Atypical Antipsychotics in South Korea: A Bibliometric Study

OBJECTIVE: We have carried out a bibliometric study on the scientific publications in relation to atypical or second-generation antipsychotic drugs (SGAs) in South Korea. METHODS: With the EMBASE and MEDLINE databases, we selected those publications made in South Korea whose title included the descriptors atypic* (atypical*) antipsychotic*, second-generation antipsychotic*, clozapine, risperidone, olanzapine, ziprasidone, quetiapine, sertindole, aripiprazole, paliperidone, amisulpride, zotepine, asenapine, iloperidone, lurasidone, perospirone and blonanserin. We applied some bibliometric indicators of paper production and dispersion with Price's law and Bradford's law, respectively. We also calculated the participation index (PI) of the different countries, and correlated the bibliometric data with some social and health data from Korea (such as total per capita expenditure on health and gross domestic expenditure on research and development). RESULTS: We collected 326 original papers published between 1993 and 2011. Our results state fulfilment of fulfilled Price's law, with scientific production on SGAs showing exponential growth (correlation coefficient r=0.8978, as against an r=0.8149 after linear adjustment). The most widely studied drugs were risperidone (91 papers), aripiprazole (77), olanzapine (53), and clozapine (43). Division into Bradford zones yielded a nucleus occupied by the Progress in Neuro-Psychopharmacology and Biological Psychiatry (36 articles). A total of 86 different journals were published, with 4 of the first 10 used journals having an impact factor being greater than 4. CONCLUSION: The publications on SGAs in South Korea have undergone exponential growth over the studied period, without evidence of reaching a saturation point.

Alternative complement pathway and factor B activities in rats with altered blood levels of thyroid hormone

Evaluating the activity of the complement system under conditions of altered thyroid hormone levels might help elucidate the role of complement in triggering autoimmune processes. Here, we investigated alternative pathway (AP) activity in male Wistar rats (180 ± 10 g) after altering their thyroid hormone levels by treatment with triiodothyronine (T3), propylthiouracil (PTU) or thyroidectomy. T3 and thyroxine (T4) levels were determined by chemiluminescence assays. Hemolytic assays were performed to evaluate the lytic activity of the AP. Factor B activity was evaluated using factor B-deficient serum. An anti-human factor B antibody was used to measure factor B levels in serum by radial immunodiffusion. T3 measurements in thyroidectomized animals or animals treated with PTU demonstrated a significant reduction in hormone levels compared to control. The results showed a reduction in AP lytic activity in rats treated with increasing amounts of T3 (1, 10, or 50 µg). Factor B activity was also decreased in the sera of hyperthyroid rats treated with 1 to 50 µg T3. Additionally, treating rats with 25 µg T3 significantly increased factor B levels in their sera (P < 0.01). In contrast, increased factor B concentration and activity (32 percent) were observed in hypothyroid rats. We conclude that alterations in thyroid hormone levels affect the activity of the AP and factor B, which may in turn affect the roles of AP and factor B in antibody production.

Physician's Role and Obligation in the Withdrawal of Life-sustaining Management

Patients should be treated with dignity and respect toward the end of their lives, being freed from unnecessary and painful life-sustaining therapy in hospitals. In Korea, the quality of endof-life (EOL) care has been variable, a major factor being the physicians' perception to the care. A firm consensus of EOL care decision-making has not yet explicitly stated in Korean law and ethics until recently. However, movements to make a law of so-called "the death with dignity act" are presently making its way to the National Assembly, initiated by a law case that allowed the hospital to withdraw mechanical ventilator support per request by the patients' family of a permanently vegetative patient. Socially agreed guidelines for EOL care can facilitate clinical decision process and communication between health service provider and the patient or his/her family. At the same time, EOL care should be individualized also in the same line of guideline to meet patient' and patient' family wish regarding the withdrawal of life-sustaining therapy. The painful EOL care experience of the loved one remains in the memory of the relatives who live on. Physicians should identify, document, respect, and act on behalf of the hospitalized patients' needs, priorities, and preference for EOL care. It has been advocated that competent patients can express their right of self-determination on EOL care through advance directives in Western countries. Advance directives are considered as a tool to facilitate EOL decision making. However, there are barriers to adopt the advance directives as a legitimate tool for an EOL decision making in Korea. For one thing, the reality of death and dying is rarely discussed in our society. In addition, the discussion about EOL care with chronically and critically ill patients has been considered as a taboo in the hospitals. In spite of these difficulties, physicians could do better EOL care by the open communication with patients or with their surrogates. Through the communication, physician should set a goal how to manage the EOL patient. The set goal should be shared among the caregivers to achieve the maximum benefit of the patient. The lack of open discussion with patient prior to EOL care results in inappropriate protraction of a patient's dying process. In summary, physicians, who know the clinical significance of delivering treatments to EOL patients, should play a central role in assisting patients' and their families' to make the best decision on EOL care. Moreover, the concerted actions to improve EOL care in our society among general public, professionals, stakeholders for EOL care, and governmental organizations are required to address ongoing social requests, although a policy or a guideline is made in this time.

Genetic variants in three genes and smoking show strong associations with susceptibility to exudative age-related macular degeneration in a Chinese population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The present study was undertaken to replicate the associations of representative polymorphisms in three genes (complement factor H (CFH), complement factor B (BF) and HtrA serine peptidase 1 (HTRA1)) with exudative age-related macular degeneration (AMD) in a Han Chinese population, and to test if the modifiable environmental factors affect AMD susceptibility associated with different type of genotype in these genes.</p><p><b>METHODS</b>An age, gender and ethnicity matched case-control study was conducted to genotype the representative single neucleotide polymorphisms (SNPs) loci including rs1061170 and rs1410996 in CFH, rs641153 and rs4151667 in BF and rs11200638 in HTRA1 gene in 144 exudative AMD patients and 126 normal controls using PCR-RFLP and direct resequencing. The demographic characteristics and behavioral risk factors were also recorded. Allelic and genotypic associations for individual SNP and joint associations with two loci were performed. The gene-gene and gene-environment interactions were analyzed using multivariate non-conditional Logistic regression analysis.</p><p><b>RESULTS</b>The C risk allele frequencies for CFH Y402H (rs1061170) in cases and controls were 12.5% and 5.4% respectively, which were much lower than those in Caucasians (P < 0.001). Compared with TT homozygous genotype, the CT heterozygous genotype was positively associated with AMD with odds ratio (OR) of 3.23 (1.36 - 5.07). However, the population attributable risk (PAR) of C allele was only 3.3% (1.4% - 4.3%). rs1410996 was also associated with AMD independent of Y402H. The ORs of exudative AMD for individuals carrying one copy risk allele and two copy risk alleles were 2.57 (1.21 - 5.45) and 4.76 (2.15 - 10.55) respectively, with correspondent PARs of 28.3% (2.0% - 40.5%) and 38.2% (21.8% - 45.4%). rs11200638 in HTRA1 was another susceptible locus for AMD and the risk homozygotes were significantly susceptible for exudutive AMD (OR = 3.98, 1.88 - 8.43) with PAR of 38.9% (24.3% - 45.8%). Education status and cigarette smoking were also related to exudative AMD. After controlling for environmental risk factors, CFH and HTRA1 SNPs were independently associated with exudative AMD, with OR of 3.50 (1.45 - 8.45) for CT genotype in Y402H, 3.34 (1.33 - 8.36) for GG genotype in rs1410996 and 3.85 (1.58 - 9.42) for AA genotype in rs11200638 respectively. The interaction analysis between gene and environmental factors showed that smoking synergistically increased susceptibility of AMD for heterozygotes of rs1410996, with OR(interaction) of 7.33 (P(interaction) = 0.029).</p><p><b>CONCLUSIONS</b>In a Han Chinese population, CFH and HTRA1 polymorphisms appear to be independently and possibly additively hereditary contributors to exudative AMD. Y402H polymorphism conferred a significant but relatively lower contribution in Chinese than in Caucasians with a low frequency of risk allele. The gene-environment interaction may be a best way to encourage those with a high genetic risk to prevent AMD by avoiding modifiable factors until there is effective treatment for AMD.</p>

Complement levels in Brazilian children during and after meningococcal meningitis

OBJETIVO: Avaliar a atividade funcional das vias clássica e alternativa do sistema complemento e os níveis de C3, C4 e fator B durante o primeiro episódio de infecção meningocócica e durante a convalescença. PACIENTES E MÉTODOS: Dez crianças brasileiras com idades entre 8 meses e 8 anos, admitidas de 1991 a 1993, com diagnóstico clínico-laboratorial de meningite meningocócica, foram estudadas durante infecção aguda (até 7 dias do diagnóstico) e no período de convalescença (entre 1 e 6 meses após). C3, C4 e fator B foram quantificados por nefelometria e a atividade lítica das vias clássica e alternativa foi avaliada por método cinético e expressa como tempo necessário para lisar 50% de uma suspensão de eritrócitos (T1/2, expresso em segundos). Baixos valores de T1/2 das vias clássica e alternativa se correlacionam com elevadas atividades de via clássica e via alternativa, respectivamente. RESULTADOS: Observaram-se diferenças significativas entre a atividade lítica da via alternativa durante a infecção e no período de convalescença (282 e 238 segundos, respectivamente, P= .01). Nenhuma diferença foi detectada nos outros parâmetros analisados. CONCLUSÕES: Na presença de meningite meningocócica a via alternativa é preferencialmente ativada, provavelmente devido à maior capacidade da endotoxina meningocócica para ativar esta via, in vivo.

Variabilidade genética dos componentes C3 e BF do sistema complemento em lúpus eritematoso sistêmico / Genetic variability of complement components C3 and BF in systemic lupus erythematosus

Objetivos - Analisar a variabilidade genética dos componentes C3 e BF do sistema complemento em pacientes brasileiros portadores de lúpus eritematoso sistêmico (LES) e as possíveis associações entre suas formas alotípicas e determinadas manifestações clínicas e laboratoriais da doença. Pacientes e métodos - O estudo foi realizado em 95 pacientes portadores de LES (88 mulheres e 7 homens, com variação etária de 14 a 57 anos, média de 30,18 anos), segundo os critérios de classificação do Colégio Americano de Reumatologia, e em 89 controles sadios. Os alótipos de C3 e de BF foram detectados no soro dos pacientes e controles através de eletroforese de alta voltagem em gel agarose, seguido de imunofixação com anticorpo específico. Resultados - Os alótipos de C3 e BF observados no presente estudo foram: C3S, C3F, C3SF, C3SS05 e BFS, BFF, BFSSF, BFSF1, BFSF075, BFSS07, BFF1. Os resultados obtidos demonstrarem aumento do alótipo BFF nos pacientes, quando comparados com os controles normais (p= 0,055; RR = 2,87); para os demais alótipos, não houve diferença signifiante quanto à sua distribuição. Menor frequência do alótipo BFS foi observada nos pacientes que apresentaram manifestações neurológicas, em relação aos que não as tiveram (p=0,059); RR = 0,28). Também nos pacientes que apresentaram serosites, observou-se frequência diminuída dos alótipos C3S e BFS, quando comparados com os que naõ apresentaram esta manifestação durante o curso da doença (p=0,036 para C3 e p=0,021 para BF; RR = 0,38 para ambos). Conclusões - A frequência diminuída de BFS nos pacientes com manifestações neurológicas e de C3S e BFS nos que apresentaram serosites no curso da doença sugere associação negativa e possível papel protetor desses alótipos no desenvolvimento dessas manifestações clínicas no LES. Os achados aqui descritos sugerem que a variabilidade genetica das proteínas C3 e BF do sistema complemento pode estar relacionada com o mecanismo etiopatogênico e com a expressão clínica do LES em pacientes brasileiros

Sistema del complemento e inmunocomplejo en el mieloma múltiple / Complement system and circulating immune complexes in multiple myeloma

Se determinó la frecuencia de 29 antígenos HLA de los loci A y B en 20 pacientes con glaucoma primario de ángulo abierto diagnósticados en el Servicio de Oftalmología del Hospital General Docente ®Enrique Cabrera¼. Se utilizaron como controles 276 personas sanas. El antígeno HLA B35 mostró asociación positiva con un riesgo relativo (RR) de 5,3. Se obtuvo una frecuencia estadísticamente significativa con una p corregida (pc) <0,002 para el HLA B35 al compararla con controles normales no relacionados. El resto de los antígenos HLA estudiados no mostraron asociación

The Effect of Milk on the Bioavailability of 6-mercaptopurine

The purine antimetabolite 6-Mercaptopurine (6-MP) has been in clinical use for over 30 years and is still a widely used agent in the treatment of childhood acute lymphoblastic leukemia. The bioavailibility, clinical efficacy and toxicity of 6-MP administered orally for maintenance therapy of children with acute lymphoblastic leukemia are highly variable in many studies, as well as at differnt times in same patient. there are many factors affecting the bioavailibility of 6-MP. The most notably factor being that concomitantly administered drugs and foods might contribute to a decrease in the bioavailibity of this drug. In our sociocultural environment milk is a major constituent of child's foods. Cow's milk contains a high concentration of xanthine oxidase, which could potentially transform 6-TM into 6-thioxanthine (6-TX) and 6-thiouric acid (6-TUA) which have no more therapeutic effects. In this study, we evaluated the effect of various milk products on the bioavailability of 6-MP. Incubation at 37degrees C for 30 min raw or pasteurized milk resulted in transformation of a large quantity of clinically relevant concentration of 6-MP into 6-TUA. The concomitant adminstration of folic acid and allopurinol has markedly inhibitory effect on the 6-MP destroying activity of milk at clinically relevant concentrations. These observations may help to optimize modalities of administration of 6-MP for the treartment of patients with childhood leukemia.

Variability of complement factor B and complement component C3 among Guarani indians from Southern Brazil

A variabilidade genética do fator B (BF) e do componente C3 do sistema complemento foi investigada numa populaçäo indígena Guarani do sul do Brasil. Foram analisados 70 indivíduos. As seguintes freqüências alélicas do loco BF foram observadas: BF*S=0,979, BF*F=0,014, BF*S05=0,007. A freqüência do alelo C3*S foi estimada em 100 por ciento. O alelo BF*S05 foi encontrado apenas em populaçöes sul-brasileiras, inclusive em índios Kaingang, o que indica que tenha se originado em indígenas sul-americanos. O baixo grau de polimorfismo de BF e o monomorfismo de C3, observado nos índios Guarani, estäo de acordo com os padröes de variabilidade observados em outras populaçöes ameríndias, esquimós e asiáticas.

Fixation of Properdin and Factor B by Bullous Pemphigoid Antibody (in vitro Study) / 대한피부과학회지

Ten serum samples from the patient with bullous pemphigoid with the baseruent mernbrane zone autoantibody titers of 320 or greater were tested, by the method of in vitro complement immunofluorescence, for their ability to fix Factor B and properdin in addition to Clq, C4 and C3. Five samples yielded positive C3 and properdin staining reaciions while four samples demonstrated positive Factor B stainings. All ten samples yieled positive C3, C4 and Clq staining reactions, Heat inactivation or treatment of the complement source with EDTA, MG2-EGTA abolished both C3, properdin and Factor B staining in all ten cases. This result suggest that pemphigoid antibody will fix properdin and Factor B in addition to Clq, C4 and C3, a phenomenon explained by assembly of the C3b amplification mechanism following activation of the classical pathway of complement system.