Increased systemic IL-6 levels point to inflammation as a determinant of renal cell carcinoma development

Introduction: Renal cell carcinoma (RCC) is one of the most prevalent kidney tumors. Inflammation is believed to be a key factor in its progression and spread since inflammatory markers are generally associated with poor prognosis in RCC patients. Cytokines are cell communication molecules involved in both healthy and pathological processes, including tumor growth and progression. Recent findings suggest that cytokine level measurements could be used for cancer monitoring and prognosis. Methods: This study characterized and compared the levels of different cytokines associated with the classical Th1, Th2, and Th17 immune responses in plasma samples from RCC patients (n = 25) and healthy controls (n = 29). Cytokine levels (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, and IL-17A) were evaluated by flow cytometry using a BD Cytometric Bead Array (CBA) kit. Results: No statistical differences in systemic IL-2, IL-4, IL-10, IL-17A, TNF, and INF-γ levels were observed between RCC patients and controls (p > 0.05). However, higher systemic IL-6 levels were observed in RCC patients (p = 0.0034). Conclusions: This study highlights the importance of assessing the impact of IL-6 on RCC pathogenesis and its potential role as a biomarker of disease progression. (AU)

Expression of 1L-myo-Inositol -1-Phosphate Synthase (EC 5.5.1.4) is Deregulated in the Cerebellum of Curly Tail Mutant Mice

Previous research, defining spatial control of inositol phosphate biosynthesis in the developing brain of CBA (normal) and CT [curly tail (ct-CT) and straight tail (st-CT)] mutant mice implicated a role for 1l-myo-inositol 1-phosphate synthase (MIP) in normal functioning of the central nervous system. Biochemical research indicated that MIP enzymatic activity, conversion of glucose 6-phosphate into inositol phosphate, is highest in the cerebellum of ct-CT and lowest in st-CT, when compared to that of CBA mice.Here, we utilized microscopic and biochemical investigations to analyze and extend previous findings of MIP expression in the cerebellum. Results of this research indicated that MIP expression correlates, well, with its enzymatic activity in the cerebellum of CBA and CT mutantmice. Statistical analyses of fluorescent micrographs detected a significant difference in fluorescence intensity between MIP from ct-CT, st-CT, and CBA mice.These data support vitallinks between inositol phosphate biosynthesis, MIP expression, and normal functioning of the cerebellum. Moreover, published data, identifying significant behavioral differences in the CT mutant, as well as data linking motor and non-motor cerebellar functions to abnormal levels of inositol, support the conclusion that aspects of normal cerebellar functions require temporal and spatial control of inositol phosphate biosynthesis, MIP expression.

Hepatic stereology of acute schistosomiasis mansoni infection in C57BL/10 and CBA mice

Estudos prévios mostraram que o curso da infecção esquistossomótica experimental depende da constituição genética do hospedeiro. A fim de testar se linhagens de camundongos infectados por Schistosoma mansoni apresentam diferenças nos padrões de patologia durante a fase aguda, examinamos possíveis alterações nos hepatócitos, sinusóides e quantidade de fibrose, utilizando uma abordagem estereológica. As mudanças na organização hepática de camundongos fêmeas, adultas, das linhagens C57BL/10 e CBA, foram examinadas oito semanas após a infecção. A densidade de volume de hepatócitos Vv(h), sinusóides Vv(s) e fibrose Vv(fh) foram examinadas por determinação do ponto de contagem (sitema-teste M42) e video microscopia, por microscopia de luz. Em ambas linhagens de camundongo, Vv(h) e Vc(s) foram significamente reduzidas (p menor que 0,05) em relação ao grupo controle. Os maiores valores de Vv(fh) foram encontradas na linhagem C57BL/10. Demonstramos que a infecção esquistossomótica reduziu acentuadamente hepatócitos (linhagem CBA) sinusóides (linhagem C57BL10), enquanto a fibrose foi maior em C57BL10 do que CBA.

Study of the re-osseointegration of implant fixture after mechanical unscrewing / 대한치과보철학회지

PURPOSE: The purpose of this study was to investigate whether the re-osseointegration of the implants that had mechanical unscrewing possibly occurred or not. Furthermore, if it happened, the degree of re-osseointegration was evaluated by comparing with previous osseointegration. MATERIALS AND METHODS: The smooth implant (commercial pure titanium 99%) specimens, whose diameter and length was 3.75 mm, 4 mm, respectively were produced. Two implants were inserted into each tibia of 7 New Zealand female white rabbits weighing at least 3.0 kg. The torque removal force for each implant after 6 weeks of implants placement was measured and included in group I . The torque removal forces were assessed after the fixtures were re-screwed to original position and the subjects were allowed to have 4 more weeks for healing and included in group II. One rabbit was sacrificed after first measurement and produced 4 slide specimens in group I, and two rabbits were sacrificed after 2nd measurement, 7 slide specimens, in group II for histomorphologic investigations. All slide specimens were assessed based on the proportion of BIC (bone-implant contact) as well as CBa (Bone area in the cortical passage) value produced by counting the screw threads embedded in the compact bones under the optical microscopic analysis (x20). Statistical analysis was conducted to evaluate the torque removal force, BIC and CBa between group I and II. RESULTS: As for the torque removal force, the result was 10.8 +/- 3.6 Ncm for group I and 20.2 +/- 9.7 Ncm for group II. Furthermore, the torque removal force of group II increased by 98.1% in average compared to group I (P .05), and RT/BIC and RT/CBa between group I and group II were statistically significant (P < .05). CONCLUSION: It is possible to obtain more substantial re-osseointegration within shorter periods than the period needed for the initial osseointegration in case of iatrogenically unscrewed implants.

Quantificação das citocinas séricas Th1/Th2 por citometria de fluxo no linfoma de Hodgkin clássico / Measurement of Th1/Th2 serum cytokines by flow cytometry in classical Hodgkin lymphoma

O linfoma de Hodgkin clássico (LHC) é uma neoplasia com distúrbio na produção de citocinas. Estudos demonstram que o padrão anormal das citocinas no linfonodo acometido pela lesão contribui não somente com a proliferação das células malignas H-RS, como também com o característico infiltrado hiper-reativo que compõe o tecido no LHC. Esta disfunção pode ser observada tanto no quadro clínico dos pacientes, como nas características histopatológicas: sintomas B, deficiência na resposta imune celular, bandas de colágeno e eosinofilia. As concentrações séricas das citocinas Th1 (IL-2, TNF, INF-γ) e Th2 (IL-4, IL-5, IL-10) foram estudadas em 45 pacientes com LHC, ao diagnóstico, e em 34 doadores saudáveis, por citometria de fluxo (CBA - cytometric beads array). Houve aumento das concentrações das citocinas TNF (p<0,01), INF-γ (p<0,01), IL-4 (p=0,01), IL-5 (p<0,01) e IL-10 (p<0,01) dos pacientes quando comparados com o grupo controle. Não foi evidenciada diferença em relação a IL-2. Ao correlacionarmos as concentrações das citocinas Th1/Th2 com as variáveis clínico-laboratoriais dos pacientes, observou-se que níveis elevados da IL-10 (Th2) estão correlacionados com as variáveis que implicam em pior prognóstico: estádios III/IV (p=0,01), presença de sintomas B (p=0,04), hemoglobina < 10,5g/dL (p=0+,01), linfócitos <600 mm³ (p=0,01) e, de acordo com o IPI, os pacientes de alto risco (p=0,01). Por outro lado, níveis séricos elevados da IL-2 (Th1) foram encontrados em estádio I/II, quando comparados com III/IV (p=0,03), o que indica que a IL-2 diminui com a progressão da doença. Os resultados sugerem que a IL-10 possa estar regulando negativamente a resposta imune citotóxica (Th1) pela inibição da IL-2. Há uma possível associação entre progressão da doença e níveis elevados da IL-10. Esse estudo evidenciou que a utilização do CBA é factível na detecção das citocinas, e que as alterações encontradas podem estar envolvidas na biologia do LHC.

Classical Hodgkin lymphoma (CHL) is a malignancy with an abnormal or unbalanced secretion/production of cytokines, which might support the growth of H-RS cells, their surrounding reactive bystander cells and may be responsible for the typical clinical and histopathologic features of CHL: systemic B symptoms, an apparent defect in cell-mediated immune response, tumor fibrosis and eosinophilic infiltrate. Serum concentrations of IL-2, IL-4, IL5, IL-10, TNF and IFN-γ (Th1/Th2) were measured in 45 patients at diagnosis of classical Hodgkin lymphoma and in 34 healthy controls by cytometric beads array (CBA). Levels of TNF (p<0.01), INF-γ(p<0.01), IL-4 (p=0.01), IL-5 (p<0.01) e IL-10 (p<0.01) were significantly higher in patients compared to the control group. No difference was observed for IL-2 between the two groups. On correlating Th1/Th2 cytokine concentrations with clinical risk factors, elevated IL-10 (Th2) levels are associated with variables that suggest worse prognoses including III/IV stage (p=0.01), B-symptoms (p=0.04), hemoglobin < 10.5g/dL (p=0.01), lymphocytes < 600/mm³ (p=0.01) and according to the seven-factored international prognostic score (IPI), a subset of patients with a particularly high risk of failure (p=0.01). Furthermore, the serum levels of IL-2 (Th1) were significantly higher in a group of I/II stage patients compared to III/IV patients (p=0.03) which implies that, the levels of IL-2 might decrease with disease progression. The elevated IL-10 levels in a subset of patients with poor clinical risk factors might down regulate a Th1 immune response by inhibiting IL-2 production causing survival disadvantage by suppression of the cytotoxic immune response against the tumor. This suggests an association between progression of CHL and higher levels of the IL-10 cytokine. This study showed that measurement of serum cytokines using the CBA methodology is highly reproducible, and that changes in concentrations...

Cost-Benefit Analysis of Back School Program for Occupational Low Back pain Patients / 예방의학회지

Although occupational low back pain accounts for 20~40% of all occupational illness and injury, there are limited numbers of studies regarding the effectiveness of back school program. The objective of this study was to evaluate the economic benefit of back school program for early return to work of occupational low back pain patients in the current occupational injury compensation and management system. The cost-benefit analysis in this study was conducted to evaluate the relative magnitude of benefit to cost. The total cost was estimated by calculating the value of components in back school program according to governmental budget protocol. The back school program was consisted of three major approaches, pain center, work-hardening program and functional restoration program and each of components had various facilities and experts. The total amount of cost was estimated as 250,866,220 won per year. The most promising type of back school program were quite intensive (a 3 to 5-week stay in a specialized center), therefore, if we adopted the 5-week stay course, 10 courses could be held in a year. Following to the medical act, 20 patients per doctor could participate in a each course, ie, total 200 patients in a year. As a result, we could estimate the cost of 1,254,331 won a patient. we estimated the benefit by using data of a few local labor offices about average medical treatment beneficiary and off-duty beneficiary of 46 occupational low back pain patients in 1994. Ullman and Larsson(1977) mentioned that the group of chronic low back pain patients who participated in back school program needed less time to recover by 48.4% of beneficiary duration. And in the trying to estimate the benefit, we asked 10 rehabilitation board certificate doctors about reduction proportion of treatment cost by introducing back school program. The answered reduction proportions were in the range of 30~45%, average 39%. As a final result, we could see that the introduction of back school program in treatment of chronic occupational low back pain patients could produce the benefit to cost ratio as 3.90 and 6.28. And we could conclude that the introduction of back school program was beneficial to current occupational injury compensation and management system.