Association between the Neutrophil-to-lymphocyte Ratio and New-onset Subclinical Macrovascular and Microvascular Diseases in the Chinese Population / 生物医学与环境科学（英文）

OBJECTIVE@#The association between neutrophil-to-lymphocyte ratio (NLR) with subclinical macrovascular and microvascular diseases has been less investigated. We sought to examine the association between NLR and new-onset subclinical macrovascular and microvascular abnormalities in the Chinese population.@*METHODS@#From a community cohort, we included 6,430 adults aged ≥ 40 years without subclinical macrovascular and microvascular diseases at baseline. We measured subclinical macrovascular and microvascular abnormalities separately using the ankle-brachial index (ABI), brachial-ankle pulse wave velocity (baPWV), and albuminuria.@*RESULTS@#During a mean follow-up of 4.3 years, 110 participants developed incident abnormal ABI, 746 participants developed incident elevated baPWV, and 503 participants developed incident albuminuria. Poisson regression analysis indicated that NLR was significantly associated with an increased risk of new-onset abnormal ABI, elevated baPWV, and albuminuria. Compared to overweight/obese participants, we found a much stronger association between NLR and subclinical vascular abnormalities in participants with normal weight. Furthermore, we found an interaction between the NLR and body mass index (BMI) on the risk of new-onset abnormal ABI ( P for interaction: 0.01).@*CONCLUSION@#NLR was associated with subclinical macrovascular and microvascular diseases in the Chinese population. Furthermore, in participants with normal weight, the association between NLR and subclinical vascular abnormalities was much stronger.

C-reactive protein and neutrophil-lymphocyte ratio as predictors of mortality in coronavirus disease 2019

SUMMARY OBJECTIVE: This study investigates whether C-reactive protein, platelet-lymphocyte ratio, and neutrophil-lymphocyte ratio could be useful to predict mortality in COVID-19. METHODS: Data of 635 patients with COVID-19 followed up in Sinop Ataturk State Hospital from February to May 2020 were evaluated retrospectively. Diagnosis of COVID-19 was made according to the interim guidance of the World Health Organization. Patients were grouped into two groups based on mortality as survived and non-survived patients. Age, gender, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and C-reactive protein of the groups were investigated and compared. RESULTS: The mean age of the participants was 55.8±22.3 years. Among the patients, 584 survived and 51 patients died. Age was significantly different between the groups, 54.2±22.3 in the survived group and 75.6±11.1 in the dead group (p=0.000). In addition, neutrophil, C-reactive protein, and neutrophil-lymphocyte ratio values were significantly higher in the dead group (p=0.000). platelet-lymphocyte ratio was slightly higher in the dead group, but this difference was not significant (p=0.42). The area under the curve values for age, lymphocyte, platelet, C-reactive protein, and neutrophil-lymphocyte ratio are 0.797, 0.424, 0.485, 0.778, and 0.729, respectively. CONCLUSIONS: Our results showed that neutrophil-lymphocyte ratio and C-reactive protein are significantly higher in patients leading to death and could be effective biomarkers in predicting COVID-19 fatality. Furthermore, C-reactive protein could be used as an independent biomarker to predict death in patients with COVID-19, regardless of gender and age (p=0.000).

Asociación entre los niveles séricos de vitamina D y marcadores inflamatorios en pacientes en hemodiálisis / Association between vitamin D serum levels and inflammatory markers in patients on hemodialysis

Resumen Introducción: La relación entre 25-OH-vitamina D y el sistema inmune en pacientes con enfermedad renal crónica es objeto de atención. Objetivos: Evaluar la prevalencia de la deficiencia de vitamina D en pacientes en hemodiálisis e investigar la asociación entre la vitamina D y proteína C reactiva ultrasensible (PCRus), índice neutrófilo/linfocito (INL) e índice plaqueta/linfocito (IPL). Método: Estudio transversal de 80 pacientes en hemodiálisis, divididos en dos grupos: un nivel sérico de 25-OH-vitamina D < 20 ng/mL se consideró como deficiencia de vitamina D y ≥ 20 ng/mL, como normal. Con el análisis de correlación de Spearman se definió la relación entre los parámetros. Resultados: 40 % de los pacientes presentó deficiencia de vitamina D. Hubo diferencias significativas entre los grupos en PCRus (p = 0.047), INL (p = 0.039), IPL (p = 0.042) y tratamiento con análogos de vitamina D (p = 0.022). La vitamina D tuvo una correlación negativa significativa con PCRus (p = 0.026), INL (p = 0.013) e IPL (p = 0.022). Conclusiones: La deficiencia de vitamina D fue de 40 %. Los niveles de PCRus, INL e IPL fueron significativamente más altos ante deficiencia de vitamina D. Se encontró correlación inversa significativa entre vitamina D y PCRus, INL e IPL.

Abstract Introduction: The relationship between 25-OH-vitamin D and the immune system in patients with chronic kidney disease is a subject of attention. Objectives: To assess the prevalence of vitamin D deficiency in patients on hemodialysis and to investigate the association between vitamin D, ultra-sensitive C-reactive protein (US-CRP), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Method: Cross-sectional study of 80 patients on hemodialysis, divided into two groups: a serum 25-OH-vitamin D level < 20 ng/mL was considered to be vitamin D deficiency and a serum level ≥ 20 ng/mL was regarded as normal. The relationship between the parameters was defined with Spearman’s correlation analysis. Results: 40 % of the patients had vitamin D deficiency. There were significant differences between groups in US-CRP (p = 0.047), NLR (p = 0.039), PLR (p = 0.042) and treatment with vitamin D analogues (p = 0.022). Vitamin D had a significant negative correlation with US-CRP (p = 0.026), NLR (p = 0.013) and PLR (p = 0.022). Conclusions: The prevalence of vitamin D deficiency was 40 %. The values of US-CRP, NLR and PLR were significantly higher in the presence of vitamin D deficiency. A significant inverse correlation was found between vitamin D levels and US-CRP, NLR and PLR.

Diagnostic value of the neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and thrombocytosis in the preoperative investigation of ovarian masses / Valor diagnóstico das razões neutrófilo/linfócito, plaqueta/ linfócito, e trombocitose na investigação pré-operatória de massas ovarianas

Abstract Objective To evaluate the diagnostic accuracy of cancer antigen 125 (CA125) and complete blood count (CBC) parameters, such as the neutrophil to lymphocyte ratio (NLR), the platelet to lymphocyte ratio (PLR), and thrombocytosis in patients with ovarian masses. Methods The present is a retrospective study conducted at a single tertiary hospital from January 2010 to November 2016. We included consecutive women referred due to suspicious adnexal masses. The CBC and CA125 were measured in the serum of 528 women with ovarian masses before surgery or biopsy. We evaluated the diagnostic performance of the NLR, PLR, platelets (PLTs), CA125, and the associations between them. We tested the clinical utility of the CBC parameters and CA125 in the discrimination of ovarian masses through decision curve analysis (DCA). Results The best balance between sensitivity and specificity was obtained by the associations of CA125 or PLTs ≥ 350/nL, with 70.14% and 71.66%, CA125 or PLTs ≥ 400/ nL, with 67.30% and 81.79%, CA125 or PLR, with 76.3% and 64.87%, and CA125 or NLR, with 71.09% and 73.89% respectively. In the DCA, no isolated CBC parameter presented a higher clinical utility than CA125 alone. Conclusion We showed that no CBC parameter was superior to CA125 in the prediction of the malignancy of ovarian tumors in the preoperative scenario.

Resumo Objetivo Avaliar a acurácia diagnóstica do antígeno de câncer 125 (cancer antigen 125, CA125, em inglês) e dos parâmetros do hemograma como as razões neutrófilo/linfócito (RNL), plaqueta/linfócito (RPL), e trombocitose em pacientes com massas ovarianas. Métodos Este é um estudo retrospectivo realizado em um hospital terciário no período de janeiro de 2010 a novembro de 2016. Foram incluídas de forma consecutiva mulheres encaminhadas por massas anexiais suspeitas. Foram dosados hemogramas e CA125 no soro de 528 mulheres com massas ovarianas antes da cirurgia ou biópsia. Foram avaliados os desempenhos diagnósticos da RNL, da RPL, das plaquetas (PLQs) e do CA125, considerando-os isoladamente e associados entre si. Testamos a utilidade clínica dos parâmetros do hemograma e do CA125 na discriminação das massas ovarianas por análise de curva de decisão (ACD). Resultados Os melhores equilíbrios entre sensibilidade e especificidade foram obtidos por meio das associações do CA125 ou PLQs ≥ 350/nL, com 70,14% e 71,66%, CA125 ou PLQs ≥ 400/nL, com 67,30% e 81,79%, CA125 ou RPL, com76,3% e 64,87%, e CA125 ou RNL, com 71,09% e 73,89%, respectivamente. Conclusão Na ACD, nenhum parâmetro do hemograma isolado se mostrou superior ao CA125 na predição de malignidade de tumores ovarianos no pré-operatório.

Increased neutrophil lymphocyte ratio and platelet lymphocyte ratio in malignant parotid tumors / Relação neutrófilo-linfócito aumentada e relação plaqueta-linfócito em tumores malignos da parótida

Abstract Introduction Recently it has been reported that a high preoperative neutrophil-lymphocyte ratio and platelet-lymphocyte ratio may be related to increased recurrence risk, tumor aggressiveness, and worsened prognosis in various malignancies. Objective The objective of this research is to explore whether neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in parotid tumors may or may not be used as a cancer marker. Methods This retrospective research has been conducted on a total of 228 patients consisting of 83 healthy persons and 145 patients with a mass in the parotid gland, who applied to a tertiary referral center and underwent surgery. Patients have been divided into two groups by their histopathological findings as malignant or benign parotid tumor. A third group consisting of healthy people has been defined as the control group. Also the malignant parotid tumor group has been divided into two subgroups as early stage and advanced stage. The groups have been compared in terms of neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and other laboratory data. Results The average neutrophil-lymphocyte ratio values of malignant parotid tumor, benign parotid tumor, healthy control groups were 2.51, 2.01, 1.79 respectively and the difference was statistically significant (p < 0.001). There was no significant difference between advanced stage and early stage parotid tumor groups in terms of average neutrophil-lymphocyte ratio value (p = 0.782). In dual comparisons, the platelet-lymphocyte ratio value of patients in the malignant group was found out to be statistically significantly higher than that of benign and control groups (p < 0.001 and p = 0.001 respectively). Conclusion To the best of our knowledge our research is the first in the medical literature comparing neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in patients with parotid tumor. neutrophil-lymphocyte ratio and platelet-lymphocyte ratio can serve as cost-effective, repeatable, easily accessible, and helpful inflammatory markers in order to distinguish patients with malignant parotid tumor from healthy people.

Resumo Introdução Recentemente, tem sido relatado que as relações neutrófilo-linfócito e plaqueta-linfócito aumentadas no pré-operatório podem estar relacionadas ao aumento do risco de recorrência e agressividade do tumor e pior prognóstico em várias neoplasias malignas. Objetivo Investigar se as relações neutrófilo-linfócito e plaqueta-linfócito em tumores da parótida podem ou não serem utilizadas como marcadores de câncer. Método Esta pesquisa retrospectiva foi conduzida com 228 indivíduos, 83 saudáveis e 145 com tumor de parótida, os quais foram encaminhados a um centro de referência terciária e operados. Os pacientes foram divididos em dois grupos de acordo com os achados histopatológicos de malignidade e benignidade. O terceiro grupo foi composto por indivíduos saudáveis, foi definido como o grupo controle. Além disso, o grupo com tumores malignos da parótida foi dividido em dois subgrupos, um com pacientes em estágio inicial da doença e o outro com pacientes em estágio avançado. Os grupos foram comparados em termos das relações neutrófilo-linfócito e plaqueta-linfócito e outros dados laboratoriais. Resultados Os valores médios da relação neutrófilo-linfócito do tumor maligno de parótida, do tumor benigno de parótida e do grupo controle foram de 2,51, 2,01 e 1,79, respectivamente, com uma diferença estatisticamente significante (p < 0,001). Não houve diferença estatística entre os grupos em estágio avançado e em estágio inicial em termos de valor médio da relação neutrófilo-linfócito (p = 0,782). Em comparações duplas, o valor da relação plaqueta-linfócito dos pacientes do grupo do grupo com tumor maligno foi estatisticamente maior do que nos grupos com tumor benigno e controle (p < 0,001 e p = 0,001, respectivamente). Conclusão Que seja de nosso conhecimento, nosso estudo é o primeiro na literatura médica a comparar a relação neutrófilo-linfócito e a relação plaqueta-linfócito em pacientes com tumor de parótida. As relações neutrófilo-linfócito e plaqueta-linfócito podem servir como marcadores inflamatórios de baixo custo, reproduzíveis, de fácil acesso e úteis, a fim de distinguir os pacientes com tumor maligno de parótida de pessoas saudáveis.

Cytotoxic, clastogenic and genotoxic effects of cis-tetraammine(oxalato)ruthenium(III) dithionate on human peripheral blood lymphocytes

There is a concern about stablishing the clinical risk of drugs used for cancer treatment. In this study, the cytotoxic, clastogenic and genotoxic properties of cis-tetraammine(oxalato)ruthenium(III) dithionite - cis-[Ru(C2O4)(NH3)4]2(S2O6), were evaluated in vitro in human lymphocytes. The mitotic index (MI), chromosomal aberrations (CA) and DNA damage by comet assay were also analyzed. The MTT test revealed that the ruthenium compound showed a slight cytotoxic effect at the highest concentration tested. The IC50 value for the compound after 24 hours of exposure was 185.4 µM. The MI values of human peripheral blood lymphocytes treated with 0.015, 0.15, 1.5 and 150 µM of cis-[Ru(C2O4)(NH3)4]2(S2O6) were 6.1, 3.9, 3.2 and 0.2%, respectively. The lowest concentration, 0.015 µM, did not show any cytotoxic activity. The CA values for the 0.015, 0.15 and 1.5 µM concentrations presented low frequency (1.5, 1.6 and 2.3%, respectively), and did not express clastogenic activity when compared to the negative control, although it was observed clastogenic activity in the highest concentration tested (150 µM). The results obtained by the comet assay suggest that this compound does not present genotoxic activity at lower concentrations. The results show that cis-[Ru(C2O4)(NH3)4]2(S2O6) has no cytotoxic, clastogenic or genotoxic in vitro effects at concentrations less than or equal to 0.015 µM. This information proves as promising in the treatment of cancer and is crucial for future trials.

Predictive value of neutrophil/lymphocyte ratio on myocardial injury in severe COVID-19 patients / 中华心血管病杂志

Objective: To explore the predictive value of neutrophil/lymphocyte ratio (NLR) on myocardial injury in severe COVID-19 patients. Methods: In this single-center retrospective cohort study, we collected and analyzed data form 133 severe COVID-19 patients admitted to Renmin Hospital of Wuhan University (Eastern District) from January 30 to February 18, 2020. Patients were divided into myocardial injury group (n=29) and non-myocardial injury group (n=104) according the presence or absence of myocardial injury. The general information of patients was collected by electronic medical record database system. All patients were followed up for 30 days, the organ injury and/or dysfunction were monitored, the in-hospital death was compared between the two groups, and the disease progression was reevaluated and classified at 14 days after initial hospitalization. Logistic regression analysis was performed to identify risk factors of myocardial injury in severe COVID-19 patients. The ROC of NLR was calculated, and the AUC was determined to estimate the optimal cut-off value of NLR for predicting myocardial injury in severe cases of COVID-19. Results: There was statistical significance in age, respiratory frequency, systolic blood pressure, symptoms of dyspnea, previous chronic obstructive pulmonary disease, coronary heart disease history, white blood cells, neutrophils, lymphocytes, platelets, C-reactive protein, platelet counting, aspartate transaminase, albumin, total bilirubin, direct bilirubin, urea, estimated glomerular filtration rate, total cholesterol, low-density lipoprotein cholesterol, D-dimer, CD3+, CD4+, partial pressure of oxygen, partial pressure of CO2, blood oxygen saturation, other organ injury, clinical outcome and prognosis between patients with myocardial injury and without myocardial injury (all P<0.05). Multivariate logistic regression analysis showed that NLR was a risk factor for myocardial injury (OR=1.066，95%CI 1.021-1.111，P=0.033). ROC curve showed that NLR predicting AUC of myocardial injury in severe COVID-19 patients was 0.774 (95%CI 0.694-0.842), the optimal cut-off value of NLR was 5.768, with a sensitivity of 82.8%, and specificity of 69.5%. Conclusion: NLR may be used to predict myocardial injury in severe COVID-19 patients.

Association of platelet to lymphocyte and neutrophil to lymphocyte ratios with in-hospital mortality in patients with type A acute aortic dissection

Abstract Objective: To evaluate the relationship between neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) with in-hospital mortality in type A acute aortic dissection (AAD). Methods: A total of 96 patients who presented to the emergency department between January 2013 and June 2018 with a diagnosis of type A AAD were enrolled in this study. White blood cell count subtypes such as NLR and PLR were calculated at the time of admission. The end point was in-hospital mortality. Results: Of the 96 type A AAD patients included in this analysis, 17 patients (17.7%) died during hospitalization. NLR and PLR were significantly elevated in patients with type A AAD (P<0.001 and <0.001, respectively). Based on the receiver operating characteristic curve, the best NLR cut-off value to predict in-hospital mortality was 9.74, with 70.6% sensitivity and 76.8% specificity, whereas the best PLR cut-off value was 195.8, with 76.5% sensitivity and 78.1% specificity. Conclusion: Admission NLR and PLR levels were important risk factors and independently associated with in-hospital mortality of type A AAD patients.

Cryopreservation of lymphocytes for immunological studies in horses / Criopreservação de linfócitos para estudos imunológicos em equinos

The use of frozen cells allows studies on diseases and other immunological assays, since it facilitates the logistics of collecting and transporting, including laboratories located in different cities or other countries. The objectives of this study were to verify if the storage in the refrigerator after collection at different times changes the viability of total leukocytes after months of freezing and the ratio of CD4/CD8 is affected by the freezing process. Venous blood of 15 healthy horses was used and the experiment was divided into 2 stages. In the first, the viability of the leukocytes before and after freezing was verified, as well as different storage times in the refrigerator (fresh blood, stored for 24 and 48 hours) before the freezing process. In the second part, the immunophenotyping of the T lymphocytes was performed, in order to observe if after thawing the relationship between LT CD4 and LT CD8 undergoes change. There was no difference between the amounts of viable leucocytes from frozen fresh blood compared to fresh blood before freezing, nor difference between the viability of blood left in the refrigerator (4°C) for 24 hours and fresh blood and fresh frozen blood. There was a decrease in viability of frozen leukocytes after 48 hours left in the freezer for other samples; however, the recovery was 107x cells. Regarding the immunophenotyping of CD2CD4+ and CD2CD8+ double-labeled T lymphocytes in the blood stored in the refrigerator for 24 hours before freezing, no difference was observed between before and after 6 months of freezing. It is concluded that cryopreservation of equine total leukocytes is possible and, although there was a difference between freezing times, even in the less viable sample, sufficient numbers of cells were recovered for other immunological assays.(AU)

A utilização de células congeladas possibilita estudos sobre doenças e outros ensaios imunológicos, pois facilita a logística de coleta e transporte, inclusive para laboratórios localizados em cidades diferentes ou outros países. Os objetivos desse estudo foram verificar se o armazenamento sobre refrigeração em diferentes tempos e a criopreservação alteram a viabilidade de leucócitos totais e se a relação entre LT CD4/CD8 é afetada pelo processo de congelamento. Utilizou-se sangue venoso de 15 cavalos hígidos e o experimento foi dividido em 2 etapas. Na primeira foi analisado se houve alteração na viabilidade dos leucócitos provenientes de amostras de sangue armazenadas em diferentes tempos em geladeira antes e depois de 6 meses de congelamento a -80°C. Na segunda parte, realizou-se a imunofenotipagem dos linfócitos T, com a finalidade de observar se após o descongelamento a relação entre LT CD4 e LT CD8 sofre alteração. Não houve diferença entre a quantidade de leucócitos viáveis da amostra de sangue fresco descongelado em relação ao sangue fresco antes do congelamento, nem diferença entre a viabilidade do sangue deixado em congelador (4°C) por 24 horas e do sangue fresco. Houve uma diminuição da viabilidade dos leucócitos, após o descongelamento de 6 meses (-80°C), das amostras de sangue deixado em geladeira por 48 horas antes do congelamento em relação às outras amostras, porém, a recuperação foi de células x107. Quanto à imunofenotipagem de linfócitos T com dupla marcação CD2CD4+ e CD2CD8+, no sangue armazenado em geladeira por 24 horas antes do congelamento, e não foi observada diferença entre antes ou depois de 6 meses de congelamento. Conclui-se que a criopreservação de leucócitos totais de equinos é possível e, embora tenha havido diferença entre os tempos de congelamento, mesmo na amostra menos viável, houve recuperação de uma quantidade de células suficientes para outros ensaios imunológicos.(AU)

Flow Cytometric White Blood Cell Differential Using CytoDiff is Excellent for Counting Blasts

BACKGROUND: The usefulness of the CytoDiff flow cytometric system (Beckman Coulter, USA) has been studied in various conditions, but its performance including rapidity in detecting and counting blasts, the most significant abnormal cells in the peripheral blood, has not been well evaluated. The objective of this study was to evaluate the performance of the CytoDiff differential counting method in challenging samples with blasts. METHODS: In total, 815 blood samples were analyzed. Samples flagged as "blasts" or "variant lymphocytes" and showing 0.8) for neutrophils and lymphocytes but poor (r<0.8) for other cells. When the cutoff value of the CytoDiff blast count was set at 1%, the sensitivity was 94.4% (95% CI; 91.2-96.6) and specificity was 91.9% (95% CI; 89.0-94.1). The positive predictive value was 88.4% (95% CI; 84.4-91.5) (304/344 cases) and negative predictive value was 96.2% (95% CI; 93.9-97.7) (453/471 cases). The CytoDiff blast counts correlated well to the manual counts (r=0.9223). CONCLUSIONS: The CytoDiff method is a specific, sensitive, and rapid method for counting blasts. A cutoff value of 1% of at least 1 type of blast is recommended for positive CytoDiff blast counts.

The First Case Report of Composite Bone Marrow Involvement by Simultaneously Developed Peripheral T-Cell Lymphoma, Not Otherwise Specified, and Diffuse Large B-Cell Lymphoma

No abstract available.

Relationship between Neutrophil-to-Lymphocyte Ratio and Plaque Components in Patients with Coronary Artery Disease: Virtual Histology Intravascular Ultrasound Analysis

The aim of this study was to evaluate the relation between neutrophil-to-lymphocyte ratio (NLR) and plaque components assessed by virtual histology-intravascular ultrasound in 399 coronary artery disease (CAD) patients with 471 coronary lesions. We classified the lesions into two groups according to the NLR on admission {low NLR group (NLR2.73 [n=101])}. By volumetric analysis, total atheroma and the absolute necrotic core (NC) volumes were significantly greater in high NLR group (249.9+/-149.7 microL vs. 192.5+/-127.7 microL, P=0.001, and 32.7+/-26.8 microL vs. 22.8+/-19.4 microL, P=0.001, respectively) and thin-cap fibroatheroma (TCFA) was observed more frequently in high NLR group (33% vs. 18%, P=0.001). ST segment elevation myocardial infarction (odds ratio [OR], 2.159; 95% CI, 1.000-4.660, P=0.050) and NLR>2.73 (OR, 1.848; 95% CI, 1.016-3.360, P=0.044) and total atheroma volume (OR, 1.003; 95% CI, 1.001-1.004, P=0.004) were the independent predictors of TCFA. CAD patients with high NLR had more vulnerable plaque components (greater NC-containing plaques) than those with low NLR.

Cell cycle inhibitory effects of leaf extract from Curcuma vamana M. Sabu & Mangaly on mitotically synchronous cultures of Physarum polycephalum Schw.

Leaf extracts of C. vamana, endemic to Kerala state in India, were found to inhibit cell cycle progression in synchronous cultures of P. polycephalum in a concentration and phase-specific manner. Crude alkaloid extract (CAE) elicited maximum cell cycle delays in comparison to soxhletted chloroform, acetone and aqueous extracts. Total alkaloid content of CAE was found to be 64.9 mg/g. CAE showed lowest DPPH radical scavenging activity. Other extracts with higher free radical scavenging activity exhibited lesser cell cycle inhibiting potential. Upto 21% decrease in nuclear DNA was observed in CAE treated samples. However, genotoxicity as evidenced by comet assay was not observed. The extracts were also found to be non-toxic to human RBCs at the highest concentration tested (750 µg/mL). CAE treatment completely suppressed a 63 kDa polypeptide with a concomitant, but weak induction of a 60 kDa polypeptide suggesting that these may be cell cycle related. CAE was found to possess potent antiproliferative activity against PBLs. The study clearly demonstrates the cell cycle inhibitory activity of C. vamana leaf extracts, with CAE being the most potent of them.

Role of the Neutrophil-Lymphocyte Count Ratio in the Differential Diagnosis between Pulmonary Tuberculosis and Bacterial Community-Acquired Pneumonia

BACKGROUND: Differential diagnosis between pulmonary tuberculosis (TB) and bacterial community-acquired pneumonia (CAP) is often challenging. The neutrophil-lymphocyte count ratio (NLR), a convenient marker of inflammation, has been demonstrated to be a useful biomarker for predicting bacteremia. We investigated the usefulness of the NLR for discriminating pulmonary TB from bacterial CAP in an intermediate TB-burden country. METHODS: We retrospectively analyzed the clinical and laboratory characteristics of 206 patients suspected of having pulmonary TB or bacterial CAP from January 2009 to February 2011. The diagnostic ability of the NLR for differential diagnosis was evaluated and compared with that of C-reactive protein. RESULTS: Serum NLR levels were significantly lower in patients with pulmonary TB than in patients with bacterial CAP (3.67+/-2.12 vs. 14.64+/-9.72, P<0.001). A NLR <7 was an optimal cut-off value to discriminate patients with pulmonary TB from patients with bacterial CAP (sensitivity 91.1%, specificity 81.9%, positive predictive value 85.7%, negative predictive value 88.5%). The area under the curve for the NLR (0.95, 95% confidence interval [CI], 0.91-0.98) was significantly greater than that of C-reactive protein (0.83, 95% CI, 0.76-0.88; P=0.0015). CONCLUSIONS: The NLR obtained at the initial diagnostic stage is a useful laboratory marker to discriminate patients with pulmonary TB from patients with bacterial CAP in an intermediate TB-burden country.

The levels of liver enzymes and atypical lymphocytes are higher in youth patients with infectious mononucleosis than in preschool children

BACKGROUND/AIMS: Infectious mononucleosis (IM) is the clinical presentation of primary infection with Epstein-Barr virus. Although the literature contains a massive amount of information on IM, most of this is related specifically to only children or adults separately. In order to distinguish any differences between preschool children and youth patients, we retrospectively analyzed their demographic and clinical features. METHODS: Records of patients hospitalized from December 2001 to September 2011 with a diagnosis of IM were retrieved from Peking University First Hospital, which is a tertiary teaching hospital in Beijing. The demographic data and clinical characteristics were collected. RESULTS: IM was diagnosed in 287 patients during this 10-year period, with incidence peaks among preschool children (15 and <24 years old, 101/287, 35.2%). Although the complaints at admission did not differ between these two patient groups, the incidence of clinical signs (tonsillopharyngitis, lymphadenopathy, hepatomegaly, and edema of the eyelids) was much higher in preschool children. The incidence of liver lesion and percentage of atypical lymphocytes were significantly higher in the youth group (P<0.001), and the average hospital stay was longer in this group. Pneumonia was the most common complication, and there was no case of mortality. CONCLUSIONS: The incidence of IM peaks among preschool children and youth patients in Beijing, China. The levels of liver enzymes and atypical lymphocytes increase with age.

Implication of Early Lymphocyte Recovery after Allogeneic Hematopoietic Stem Cell Transplantation in Children with Leukemia

PURPOSE: The repopulating lymphocytes after allogeneic hematopoietic stem cell transplantation have an important role not only on the prevention of serious infections in the early transplantation period, but also on the killing of residual leukemic cells by graft-versus-leukemia effect. The aim of this study was to analyze the impact of lymphocyte recovery after allogeneic stem cell transplantation in children with hematologic malignancies. MATERIALS AND METHODS: We evaluated 69 children transplanted for acute lymphoblastic leukemia (ALL) (n=34), acute myeloid leukemia (AML) (n=26), chronic leukemia (n=7) and juvenile myelomonocytic leukemia (n=2) between 1996 and 2008 at the Chonnam National University Hospital, Korea. The patients were grouped based on absolute lymphocyte counts (ALC) or =500/microL at D+21 and D+30 after transplant. RESULTS: Patients with a High ALC at D+21 and D+30 had a faster neutrophil and platelet engraftment. The High at D+30 group had a better 5 year overall survival (71% vs. 53%, p=0.043) and event-free survival (72% vs. 53%, p=0.065) than the Low at D+30 group. The incidence of grade II-IV acute and chronic graft-versus-host disease (GVHD), and relapse rate did not differ by the ALC counts. However, the Low at D+30 group had a significantly increased risk for transplant-related mortality (p=0.019). The univariate analysis showed that the factors associated with decreased survival were a Low ALC at D+30, patients with high risk ALL, and grade II-IV aGVHD in patients with ALL and AML. CONCLUSION: Early posttransplant serial lymphocyte measurement would be a simple but useful method for predicting transplant outcomes.

Antiviral effect of dietary germanium biotite supplementation in pigs experimentally infected with porcine reproductive and respiratory syndrome virus

Germanium biotite (GB) is an aluminosilicate mineral containing 36 ppm germanium. The present study was conducted to better understand the effects of GB on immune responses in a mouse model, and to demonstrate the clearance effects of this mineral against Porcine reproductive and respiratory syndrome virus (PRRSV) in experimentally infected pigs as an initial step towards the development of a feed supplement that would promote immune activity and help prevent diseases. In the mouse model, dietary supplementation with GB enhanced concanavalin A (ConA)-induced lymphocyte proliferation and increased the percentage of CD3+CD8+ T lymphocytes. In pigs experimentally infected with PRRSV, viral titers in lungs and lymphoid tissues from the GB-fed group were significantly decreased compared to those of the control group 12 days post-infection. Corresponding histopathological analyses demonstrated that GB-fed pigs displayed less severe pathological changes associated with PRRSV infection compared to the control group, indicating that GB promotes PRRSV clearance. These antiviral effects in pigs may be related to the ability of GB to increase CD3+CD8+ T lymphocyte production observed in the mice. Hence, this mineral may be an effective feed supplement for increasing immune activity and preventing disease.

Response of the G2-prophase checkpoint to genotoxic drugs in lymphocytes from healthy individuals

We analyzed the in vitro effects of the anti-tumoral drugs doxorubicin, cytosine arabinoside and hydroxyurea on the G2-prophase checkpoint in lymphocytes from healthy individuals. At biologically equivalent concentrations, the induced DNA damage activated the corresponding checkpoint. Thus: i) there was a concentration-dependent delay of G2 time and an increase of both the total DNA lesions produced and repaired before metaphase and; ii) G2-checkpoint adaptation took place as chromosome aberrations (CAs) started to appear in the metaphase, indicating the presence of unrepaired double-strand breaks (DSBs) in the previous G2. The checkpoint ATM/ATR kinases are involved in DSB repair, since the recorded frequency of CAs increased when both kinases were caffeine-abrogated. In genotoxic-treated cells about three-fold higher repair activity was observed in relation to the endogenous background level of DNA lesions. The maximum rate of DNA repaired was 3.4 CAs/100 metaphases/hour, this rise being accompanied by a modest 1.3 fold lengthening of late G2 prophase timing. Because of mitotic chromosome condensation, no DSBs repair can take place until the G1 phase of the next cell cycle, when it occurs by DNA non-homologous end joining (NHEJ). Chromosomal rearrangements formed as a consequence of these error-prone DSB repairs ensure the development of genome instability through the DNA-fusion-bridge cycle. Hence, adaptation of the G2 checkpoint supports the appearance of secondary neoplasia in patients pretreated with genotoxic drugs.

Duodenal nodularity in children: A clinical and pathologic study of 17 cases.

Aims: Duodenal nodularity is an uncommon endoscopic appearance of numerous visible mucosal nodules in the proximal duodenum. In this retrospective study we aimed to determine the clinical significance and histopathologic features of duodenal nodularity in children. Materials and Methods: The medical records of the patients who were defined to have duodenal nodularity by endoscopy were reviewed. Statistical Analysis Used: The data were expressed as mean ± SD and percentages (%). Results: Seventeen patients with endoscopically defined duodenal nodularity were chosen. The mean age at diagnosis was 12.1 years (range: 6-17 years), 9 males. Abdominal pain (47%) was the most common clinical symptom and antral nodularity (41%) was the most common endoscopic finding in children with duodenal nodularity. Histopathologic evaluation of duodenal nodules revealed chronic inflammation in all patients, increased intercryptal and intraepithelial numbers of eosinophils in 70.5%, and villous atrophy in 47% of patients. Giardia infestation was demonstrated in 6 patients by histologic examination and/or Giardia lamblia-specific antigen positivity in stools. The clinical diagnoses of the patients have shown variations, such as celiac disease, giardiasis, secretory IgA deficiency, and Helicobacter pylori gastritis, and some of them were associated with the others. Conclusions: Although the endoscopic appearance is similar, clinical spectrum and pathologic features are not so similar and there are no specific histomorphologic findings for nodularity. The most demonstrative findings we observed in children were increased lymphocyte and/or eosinophil infiltration in the duodenal mucosa. We suggested that care should be taken in the evaluation of microbiological and immunologic etiologies causing this prominent inflammatory reaction.

Efeitos da radiação solar crônica prolongada sobre o sistema imunológico de pescadores profissionais em Recife (PE), Brasil / Effects of long-term chronic exposure to sun radiation in immunological system of commercial fishermen in Recife, Brazil

FUNDAMENTOS: Existe um consenso de que a exposição à radiação ultravioleta determina alterações n o sistema imunológico da pele, o que permite que se avente a hipótese de que a exposição prolongada e crônica ao Sol pode representar uma das maiores agressões ambientais à saúde humana. Entre as várias ocupações que requerem, necessariamente, exposição prolongada e crônica ao Sol está a de pescador. No entanto, a experiência clínica dermatológica, amealhada ao longo de vários anos de exercício da Medicina, não parece confirmar essa hipótese. OBJETIVO: Avaliar efeitos clínicos, histológicos e imunológicos da exposição crônica e prolongada à radiação ultravioleta em pescadores. MÉTODOS: Em estudo prospectivo, transversal, observacional, foram caracterizadas lesões dermatológicas, marcadores imunológicos e alterações histológicas de pescadores e subpopulações de linfócitos comparadas a grupo-controle. Empregaram-se testes de Mann-Whitney, exato de Fisher, Wilcoxon em nível de 0,05. RESULTADOS: Houve diferenças entre os grupos exposto e protegido em elastose (p = 0,03), ectasia de vasos dérmicos (p = 0,012) e número de células nas camadas epidérmicas entre os cones (p = 0,029). Foram mais comuns em pescadores CD45RO, CD68+ e mastócitos na pele (p = 0,040, p < 0,001 e p = 0,001); CD3CD8CD45RO no sangue (p = 0,016). CONCLUSÃO: As alterações sugerem que exposição crônica e prolongada ao sol promove tolerância à radiação ultravioleta, protetora da imunossupressão.

BACKGROUND: Among the various occupations which necessarily require long-term and chronic sun exposure is that of a fisherman. However, clinical experience in dermatology earned over several years of medical practice does not seem to confirm this hypothesis. OBJECTIVE: To evaluate clinical, histological and immunological effects of long-term and chronic exposure to ultraviolet radiation in fishermen. METHODS: A prospective, cross-sectional and observational study characterized skin lesions, immunological markers and histological alterations in fishermen, as well as lymphocyte subpopulations compared to a control group. Mann-Whitney, Fisher's and Wilcoxon statistical tests were used at a significance level of 0.05. RESULTS: There were significant differences between the exposed group and the group protected due to elastosis (p = 0.03), ectasia of dermal vessels (p = 0.012) and number of cells in the epidermal layers between cones (p = 0.029). Most common among fishermen were CD45RO, CD68 + and mastocytes in the skin (p = 0.040, p <0.001, p = 0.001) and CD3CD8CD45RO in the blood (p = 0.016). CONCLUSION: The alterations suggest that long-term and chronic sun exposure promotes tolerance to ultraviolet radiation, which protects against immunosuppression.