Human Papillomavirus 16 Lineage D is Associated with High Risk of Cervical Cancer in the Brazilian Northeast Region.

OBJECTIVE: Similar to Human Papillomavirus (HPV) genotypes, different lineages of a genotype also have different carcinogenic capabilities. Studies have shown that specific genotype lineages of oncogenic HPV are associated with variable risks for the development of cervical intraepithelial neoplasia (CIN2/CIN3) and cervical cancer. The present study aimed to analyze the genetic diversity of the HPV16 genotype in women with CIN2/CIN3 and cervical cancer, from the northeast region of Brazil. METHODS: A cross-sectional multicenter study was conducted in the northeast region of Brazil, from 2014 to 2016. This study included 196 cases of HPV16 variants (59 and 137 cases of CIN2/CIN3 and cervical cancer, respectively). The difference of proportion test was used to compare patients with CIN2/CIN3 and cervical cancer, based on the prevalent HPV16 lineage (p < 0.05). RESULTS: According to the histopathological diagnosis, the percentage of lineage frequencies revealed a marginal difference in the prevalence of lineage A in CIN2/CIN3, compared with that in cervical cancer (p = 0.053). For lineage D, the proportion was higher in cancer cases (32.8%), than in CIN2/CIN3 cases (16.9%), with p = 0.023. CONCLUSION: HPV16 lineage A was the most frequent lineage in both CIN2/CIN3 and cervical cancer samples, while lineage D was predominant in cervical cancer, suggesting a possible association between HPV16 lineage D and cervical cancer.

OBJETIVO: Tanto os tipos quanto as linhagens do Papilomavírus Humano (HPV) parecem ter diferentes capacidades carcinogênicas e estão associados a riscos variados para o desenvolvimento de neoplasia intraepitelial cervical (NIC) e câncer de colo do útero. O presente estudo tem como objetivo analisar a diversidade genética do genótipo HPV 16 nos casos de NIC2/NIC3 e câncer de colo de útero em mulheres da região Nordeste do Brasil. MéTODOS: Estudo transversal de base hospitalar realizado na região Nordeste do Brasil no período de 2014 a 2016. A amostra foi composta por 196 casos da variante HPV-16 (59 casos de NIC2/NIC3 e 137 de câncer do colo do útero). O teste de diferença de proporção foi usado para comparar os grupos NIC2/NIC3 e câncer de colo do útero por linhagem viral em relação à prevalência da linhagem HPV-16. Foi considerada significância estatística o valor de p < 0,05. RESULTADOS: As frequências de linhagem por diagnóstico histopatológico mostraram diferença limítrofe da linhagem A no grupo NIC2/NIC3 em relação ao grupo câncer de colo de útero (p = 0,053). Por outro lado, em relação à linhagem D, houve uma proporção maior nos casos de câncer (32,8%) quando comparado ao grupo NIC2/NIC3 (16,9%) e esta diferença se mostrou estatisticamente significante (p = 0,023). CONCLUSãO: A linhagem A do HPV-16 foi a mais frequente tanto nas amostras CIN2/CIN3 quanto nas amostras de câncer de colo de útero, enquanto a linhagem D predominou no câncer de colo do útero, sugerindo uma possível associação da linhagem D de HPV-16 com câncer de colo de útero.

Analyses of the soluble levels of sCD40L, sCD62P and sCD40 in pediatric sickle cell anemia patients with abnormal transcranial Doppler.

INTRODUCTION: Serum levels of sCD40L, sCD40 and sCD62P were evaluated in sickle cell anemia (SCA) patients aged between 2 and 16 years with normal transcranial Doppler (TCD) and no stroke (G1, n = 24); in SCA patients with abnormal TCD (G2, n = 16); in SCA patients with a previous history of stroke (G3, n = 8), and; in healthy controls (aged 2 to 13 years; n = 26). RESULTS: The levels of sCD40L were significantly higher in the G1, G2 and G3 groups, compared to controls (p = 0.0001, p < 0.0002 and p = 0.004, respectively). Among patients with SCA, higher levels of sCD40L were found in the G3 group, compared to the G2 group (p = 0.03). In the sCD62P analysis, high levels in G3, compared to G1 (p = 0.0001), G2 (p = 0.03) and G4 (p = 0.01), and G2 also had high levels, compared to G1 (p = 0.04). The G1 patients had a higher sCD40L/sCD62P ratio, compared to G2 (p = 0.003) and controls (p < 0.0001). The sCD40L/sCD40 ratios were higher in G1, G2 and G3, compared to controls (p < 0.0001, p = 0.008 and p = 0.002, respectively). CONCLUSION: It was concluded that the combination of TCD abnormality, associated with levels of sCD40L and sCD62P, may contribute to a better assessment of the risk for stroke in pediatric SCA patients. Favor pedir para os autores corrigirem esta frase, pois NÃO é uma sentença completa em inglês: Our data suggest that decreased values of the s[LSM1] CD40L/sCD62P ratio involving two inflammatory mediators produced in platelet activation, being unprecedented in the literature.

Prognostic utility of SOX2, STAT3, and CD44high/CD24low expression in penile cancer.

PURPOSE: Penile cancer has a high incidence in developing countries. The standard treatment is removal of the primary tumor and, when necessary, inguinal lymphadenectomy. Currently, the most important prognostic factor is lymph node disease, however, the available staging methods are inaccurate, and the high morbidity rate of lymphadenectomy has stimulated the study of predictive biomarkers of lymph node metastasis for selecting the patients who need lymphadenectomy. SOX2, STAT3 and CD44high/CD24low were chosen because they have provided good predictive results in other squamous cell carcinoma (SCC), although there are no studies for penile cancer. Thus, the expression of SOX2, STAT3, CD24+, and CD44+ in the penile cancer tumor microenvironment was investigated for correlation with tumor behavior in SCC. METHODS: This observational, prospective, translational study included 34 men and investigated the expression of SOX2, STAT3, CD24+, and CD44+ in tumor tissue by flow cytometry. RESULTS: The median age of the 38 evaluated patients with penile cancer was 61 (37-80) years. Most patients presented a tumor located on the glans penis (82.3%), with the usual histological type (79.4%) and 61.7% of patients presented stage pT2. No metastasis was found in 85.3% of patients. The expression of SOX2, STAT3 and CD44high/CD24low in the microenvironment of penile SCC treated with lymphadenectomy was significantly associated with aggressive tumor behavior (p < 0.05). STAT3 expression shows discrepant points when evaluated in context of angiolymphatic vascular invasion. CONCLUSION: SOX2, STAT3 and CD44high/CD24low in penile SCC can be indicators of prognosis, allowing for selection of more aggressive treatment when necessary.

Human Papillomavirus 16 Lineage D is Associated with High Risk of Cervical Cancer in the Brazilian Northeast Region / Papillomavirus humano 16 da linhagem D associado a alto risco de câncer de colo do útero em região do nordeste brasileiro

Abstract Objective Similar to Human Papillomavirus (HPV) genotypes, different lineages of a genotype also have different carcinogenic capabilities. Studies have shown that specific genotype lineages of oncogenic HPV are associated with variable risks for the development of cervical intraepithelial neoplasia (CIN2/CIN3) and cervical cancer. The present study aimed to analyze the genetic diversity of the HPV16 genotype in women with CIN2/CIN3 and cervical cancer, from the northeast region of Brazil. Methods A cross-sectional multicenter study was conducted in the northeast region of Brazil, from 2014 to 2016. This study included 196 cases of HPV16 variants (59 and 137 cases of CIN2/CIN3 and cervical cancer, respectively). The difference of proportion test was used to compare patients with CIN2/CIN3 and cervical cancer, based on the prevalent HPV16 lineage (p < 0.05). Results According to the histopathological diagnosis, the percentage of lineage frequencies revealed a marginal difference in the prevalence of lineage A in CIN2/CIN3, compared with that in cervical cancer (p = 0.053). For lineage D, the proportion was higher in cancer cases (32.8%), than in CIN2/CIN3 cases (16.9%), with p = 0.023. Conclusion HPV16 lineage A was the most frequent lineage in both CIN2/CIN3 and cervical cancer samples, while lineage D was predominant in cervical cancer, suggesting a possible association between HPV16 lineage D and cervical cancer.

Resumo Objetivo Tanto os tipos quanto as linhagens do Papilomavírus Humano (HPV) parecem ter diferentes capacidades carcinogênicas e estão associados a riscos variados para o desenvolvimento de neoplasia intraepitelial cervical (NIC) e câncer de colo do útero. O presente estudo tem como objetivo analisar a diversidade genética do genótipo HPV 16 nos casos de NIC2/NIC3 e câncer de colo de útero em mulheres da região Nordeste do Brasil. Métodos Estudo transversal de base hospitalar realizado na região Nordeste do Brasil no período de 2014 a 2016. A amostra foi composta por 196 casos da variante HPV-16 (59 casos de NIC2/NIC3 e 137 de câncer do colo do útero). O teste de diferença de proporção foi usado para comparar os grupos NIC2/NIC3 e câncer de colo do útero por linhagem viral em relação à prevalência da linhagem HPV-16. Foi considerada significância estatística o valor de p < 0,05. Resultados As frequências de linhagem por diagnóstico histopatológico mostraram diferença limítrofe da linhagem A no grupo NIC2/NIC3 em relação ao grupo câncer de colo de útero (p = 0,053). Por outro lado, em relação à linhagem D, houve uma proporção maior nos casos de câncer (32,8%) quando comparado ao grupo NIC2/NIC3 (16,9%) e esta diferença se mostrou estatisticamente significante (p = 0,023). Conclusão A linhagem A do HPV-16 foi a mais frequente tanto nas amostras CIN2/CIN3 quanto nas amostras de câncer de colo de útero, enquanto a linhagem D predominou no câncer de colo do útero, sugerindo uma possível associação da linhagem D de HPV-16 com câncer de colo de útero.

Analysis of physical activity and plasma levels of soluble CD40 and CD40L in older people with gastrointestinal tract cancer.

Regular physical activity prevents and treats cancer patients by assisting and improving the immune system. Co-stimulatory molecules that activate the immune system have been studied in cancer, such as immune checkpoint molecules of the CD40/CD40L pathway. This study aimed to characterize plasma levels of soluble CD40 (sCD40) and CD40 ligand (sCD40L) in older people with gastrointestinal tract (GIT) cancer and associate results with physical activity. This prospective and exploratory cohort study was performed with 24 older people with GIT cancer and 23 healthy elderly individuals as controls. Physical activity level was classified as active or sedentary according to the International Physical Activity Questionnaire-Short Form (IPAQ-SF). Plasma levels of sCD40 and sCD40L were determined using Enzyme-Linked Immunosorbent Assay. Plasma levels of sCD40 were higher, while sCD40L were lower (p = 0.0171) in older people with GIT cancer than controls (p = 0.0038). Regarding physical activity, active older people with GIT cancer presented lower plasma levels of sCD40 and sCD40L than those sedentary with GIT cancer (p = 0.0228 and p = 0.0236), respectively. Our findings suggest that GIT cancer stimulates the immune system in older people, elevates levels of sCD40, and reduces levels of sCD40L. Physical activity may be a protective factor for the immune system of these patients since it acts on sCD40/sCD40L pathway.

Study on collagen parameters in vulvar cancer and preneoplastic lesions by Second Harmonic Generation microscopy.

The extracellular matrix plays an important role in cellular balance, and collagen fibers are its most important component. Over the last few years, second harmonic generation (SHG) microscopy has been used for the analysis of collagen fibers in several types of gynaecological cancers, such as breast and ovarian cancer. The value of collagen parameters obtained with this technique to gain insights on the physiopathology and on the prognostic evaluation of cancer has been advocated. Herein, we have characterized the collagen fibers in squamous cell carcinoma (VSCC) and preneoplastic lesions using the SHG microscopy. Collagen parameters, quantity, organization, and uniformity, of VSCC, adjacent skin of VSCC or preneoplastic lesions were compared with values obtained in normal tissue of healthy control. There was an evident decrease in the values of collagen fiber parameters in the VSCC. Increased quantity and uniformity of tumor associated collagen fibers were associated with the presence of lymph node metastases, which suggest a prognostic value of such parameters in the evaluation of vulvar cancer.

Interleukin-6 in pregnancy with sickle cell disease

ABSTRACT Background: Despite advances in health care for sickle cell disease patients, as well as in the improvement in reproductive issues mainly in women with the disease, pregnancy is still a challenge, both for the mother and the child, with high rates of maternal and fetal morbidity and mortality. Besides their chronic hemolytic status and vaso-occlusive events that confer systemic complications, pregnant women also have higher rates of pain episodes, infections, abortion, intrauterine growth retardation, pre-term births, eclampsia, stillbirth and the hemolysis, elevated liver enzymes and low platelets syndrome. The physiologic mechanisms of the disease in pregnancy are still unknown and chronic inflammatory responses may interfere in the adverse outcomes. The cytokine and chemokine profiles in pregnancy with sickle cell disease remain unknown. The aim of this study was to evaluate the cytokine profile of the inflammatory response of pregnant women with sickle cell disease. Method: Blood samples from 20 pregnant women with sickle cell disease, 24 women with sickle cell disease in steady state, 16 healthy pregnant women and a control group with 9 women at childbearing age were assayed for interleukin-6. Main results: Pregnant women with sickle cell disease presented high serum levels of interleukin-6, compared to healthy pregnant women (p = 0.0115). Conclusion: These data suggest that the increased production of interleukin-6 may occur during pregnancy with sickle cell disease and that the role of this cytokine in the sickle cell disease pathophysiology and pregnancy complications should be further studied.

Effect of spironolactone on the progression of coronary calcification in peritoneal dialysis patients: a pilot study / Efeito da espironolactona na progressão da calcificação coronariana em pacientes em diálise peritoneal: um estudo piloto

ABSTRACT Introduction: There is evidence that aldosterone plays a role in the pathogenesis of vascular calcification. The aim of this study was to evaluate the effect of spironolactone, a mineralocorticoid receptor antagonist, on the progression of coronary calcification (CC) in peritoneal dialysis patients and to identify the factors involved in this progression. Methods: Thirty-three patients with a coronary calcium score (CCS) ≥ 30, detected through multi-detector computed tomography (MDCT) and expressed in Agatston units, were randomly assigned to a group receiving 25mg spironolactone per day for 12 months (spironolactone group) and a control group not receiving this drug. The primary outcome was a percentage change in CCS from baseline to end of the study (relative progression), when a further MDCT was conducted. Patients who had progression of CC were compared with those who did not progress. Results: Sixteen patients, seven in the spironolactone group and nine in the control group, concluded the study. The relative progression of the CCS was similar in both groups, 17.2% and 27.5% in the spironolactone and control groups respectively. Fifty-seven percent of the treated patients and 67% of those in the control group presented progression in the CC scores (p = 0.697). Progressor patients differed from non-progressors because they presented higher levels of calcium and low-density lipoprotein cholesterol and lower levels of albumin. Conclusion: In peritoneal dialysis patients, spironolactone did not attenuate the progression of CC. However, large-scale studies are needed to confirm this observation. Disorders of mineral metabolism and dyslipidemia are involved in the progression of CC.

RESUMO Introdução: Existem evidências de que a aldosterona exerça um papel na patogênese da calcificação vascular. O objetivo deste estudo foi avaliar o efeito da espironolactona, um antagonista do receptor mineralocorticoide, na progressão da calcificação coronariana (CC) de pacientes em diálise peritoneal, e identificar os fatores envolvidos nessa progressão. Métodos: Trinta e três pacientes com escore de cálcio coronariano (ECC) ≥ 30, detectado por tomografia computadorizada com múltiplos detectores (TCMD) e expresso em unidades de Agatston, foram randomizados para um grupo que recebeu 25 mg de espironolactona por dia durante 12 meses (grupo espironolactona) e um grupo controle que não recebeu este medicamento. O desfecho primário foi a mudança percentual do ECC do início para o final do estudo (progressão relativa), quando uma nova TCMD foi realizada. Os pacientes que tiveram progressão de CC foram comparados com aqueles que não progrediram. Resultados: Dezesseis pacientes, sete no grupo espironolactona e nove no grupo controle, concluíram o estudo. A progressão relativa do ECC foi semelhante nos dois grupos, 17,2% e 27,5% nos grupos espironolactona e controle, respectivamente. Cinquenta e sete por cento dos pacientes tratados e 67% daqueles no grupo controle apresentaram progressão nos escores de CC (p = 0,697). Os pacientes progressores diferiram dos não progressores porque apresentaram níveis séricos mais elevados de cálcio e LDL-colesterol e menores níveis de albumina. Conclusão: Em pacientes em diálise peritoneal, a espironolactona não atenuou a progressão da CC. No entanto, estudos em grande escala são necessários para confirmar essa observação. Distúrbios do metabolismo mineral e dislipidemia estão envolvidos na progressão da CC.

MicroRNA expression profiling provides novel insights into immune-related pathways involved in gastric cancer.

Gastric cancer is one of the most common cancers, and an increasing number of studies have found that microRNAs (miRNAs) play essential roles in gastric cancer progression; however, the roles of specific miRNAs involved in the immune response to this disease remain unclear. We compared the miRNA expression in tissues from primary gastric cancer patients and healthy controls to find miRNAs dysregulated in gastric cancer and used bioinformatics tools to determine potential roles of these miRNAs in the immune system. We evaluated 25 primary gastric cancer tissues and five healthy gastric tissues. Quantitative real-time polymerase chain reaction was performed for a set of miRNAs, followed by the prediction of their target genes and functional enrichment analysis of these targets. Analysis of a microarray dataset showed that the miRNA miR-196a-5p was significantly upregulated, while miR-374a-5p and miR-375 were downregulated in gastric cancer patients. In addition, miR-374-5p was significantly downregulated in patients with metastasis compared with its expression levels in non-metastatic patients (p = 0.03). Bioinformatics analysis suggested that the pathways regulated by these differentially expressed miRNAs were related to the immune response, cell adhesion, and cell migration. Most importantly, this study provides a new insight into the potential use of multiple miRNAs to find distinct pathways of immune regulation in gastric cancer.

Effect of spironolactone on the progression of coronary calcification in peritoneal dialysis patients: a pilot study.

INTRODUCTION: There is evidence that aldosterone plays a role in the pathogenesis of vascular calcification. The aim of this study was to evaluate the effect of spironolactone, a mineralocorticoid receptor antagonist, on the progression of coronary calcification (CC) in peritoneal dialysis patients and to identify the factors involved in this progression. METHODS: Thirty-three patients with a coronary calcium score (CCS) ≥ 30, detected through multi-detector computed tomography (MDCT) and expressed in Agatston units, were randomly assigned to a group receiving 25mg spironolactone per day for 12 months (spironolactone group) and a control group not receiving this drug. The primary outcome was a percentage change in CCS from baseline to end of the study (relative progression), when a further MDCT was conducted. Patients who had progression of CC were compared with those who did not progress. RESULTS: Sixteen patients, seven in the spironolactone group and nine in the control group, concluded the study. The relative progression of the CCS was similar in both groups, 17.2% and 27.5% in the spironolactone and control groups respectively. Fifty-seven percent of the treated patients and 67% of those in the control group presented progression in the CC scores (p = 0.697). Progressor patients differed from non-progressors because they presented higher levels of calcium and low-density lipoprotein cholesterol and lower levels of albumin. CONCLUSION: In peritoneal dialysis patients, spironolactone did not attenuate the progression of CC. However, large-scale studies are needed to confirm this observation. Disorders of mineral metabolism and dyslipidemia are involved in the progression of CC.

Interleukin-6 in pregnancy with sickle cell disease.

BACKGROUND: Despite advances in health care for sickle cell disease patients, as well as in the improvement in reproductive issues mainly in women with the disease, pregnancy is still a challenge, both for the mother and the child, with high rates of maternal and fetal morbidity and mortality. Besides their chronic hemolytic status and vaso-occlusive events that confer systemic complications, pregnant women also have higher rates of pain episodes, infections, abortion, intrauterine growth retardation, pre-term births, eclampsia, stillbirth and the hemolysis, elevated liver enzymes and low platelets syndrome. The physiologic mechanisms of the disease in pregnancy are still unknown and chronic inflammatory responses may interfere in the adverse outcomes. The cytokine and chemokine profiles in pregnancy with sickle cell disease remain unknown. The aim of this study was to evaluate the cytokine profile of the inflammatory response of pregnant women with sickle cell disease. METHOD: Blood samples from 20 pregnant women with sickle cell disease, 24 women with sickle cell disease in steady state, 16 healthy pregnant women and a control group with 9 women at childbearing age were assayed for interleukin-6. MAIN RESULTS: Pregnant women with sickle cell disease presented high serum levels of interleukin-6, compared to healthy pregnant women (p=0.0115). CONCLUSION: These data suggest that the increased production of interleukin-6 may occur during pregnancy with sickle cell disease and that the role of this cytokine in the sickle cell disease pathophysiology and pregnancy complications should be further studied.

Evaluation of immunological parameters in pregnant women: low levels of B and NK cells / Avaliação dos parâmetros imunológicos em mulheres gestantes: baixos níveis de células B e NK

Abstract Objective To describe the immunological and hematological reference intervals of low-risk pregnant women. Methods A cross-sectional retrospective database analysis of a basic and translational study analyzing the hematological evaluation blood counts and immunophenotyping of TCD3 + , TCD4 + , TCD8 + , B, and natural killer (NK) cells of the peripheral blood in 79 low-risk pregnant women and of 30 control women from the state of Pernambuco, Brazil, was performed. Results No significant differences were detected between the hematological profiles of the 2nd and 3rd trimesters. Nevertheless, the median level of B cells decreased significantly in the 2nd (174 x 103 μL; p < 0.002) and 3rd trimesters (160 x 103 μL; p < 0.001), compared with the control group (296 x 103 μL). Similarly, the median level of NK cells was lower in the 2nd (134 x 103 μL; p < 0.0004) and 3rd trimesters (100 x 103 μL, p < 0.0004), compared with the control group (183 x 103 μL). In contrast, relative TCD4+ and TCD8+ levels increased in the 2nd and 3rd trimesters compared with the controls (TCD4 + : 2nd trimester = 59%; p < 0.001; 3rd trimester = 57%; p < 0.01; control = 50%; and TCD8 + : 2nd trimester = 31%; p < 0.001; 3rd trimester = 36%; p < 0.01; control = 24%). Conclusion Low-risk pregnant women have ~ 40% less B and NK cells in the peripheral blood, compared with non-pregnant women. These parameters may improve health assistance for mothers and contribute to define reference values for normal pregnancies.

Resumo Objetivo Descrever o intervalo de referência imunológico e hematológico de gestantes de baixo risco. Métodos Realizou-se uma análise retrospectiva, de um estudo básico e translacional, analisando o perfil hematológico e a imunofenotipagem das células TCD3 + , TCD4 + , TCD8 + , B e natural killer (NK) do sangue periférico de 79 gestantes de baixo risco e de 30 mulheres (controles) do estado de Pernambuco, Brasil. Resultados Não observamos diferenças significativas entre os perfis hematológicos do 2° e 3° trimestres. No entanto, houve redução das células B no 2° (média = 174 x 103 μL; p < 0,002) e no 3° trimestres (160 x 103 μL; p < 0,001), comparado como grupo controle (296 x 103 μL). A mediana das células NK foi menor no 2° (134 x 103 μL; p < 0,0004) e no 3° trimestres (100 x 103 μL; p < 0,0004), comparado com o grupo controle (183 x 103 μL). Porém, o percentual de TCD4+ e de TCD8+ aumentou no 2° e 3° trimestres em relação aos controles (TCD4 + : 2° trimestre = 59%; p < 0,001; 3° trimestre = 57%; p < 0,01; controle = 50%; e TCD8 + : 2° trimestre = 31%; p < 0,001; 3° trimestre = 36%; p < 0,01; controle = 24%). Conclusão Mulheres grávidas de baixo risco têm ~ 40% menos células B e NK no sangue periférico em comparação com mulheres não grávidas. Estes parâmetros podem melhorar a assistência à saúde das mães e contribuir para a definição de valores de referência para gestações normais.

Evaluation of Immunological Parameters in Pregnant Women: Low Levels of B and NK Cells.

OBJECTIVE: To describe the immunological and hematological reference intervals of low-risk pregnant women. METHODS: A cross-sectional retrospective database analysis of a basic and translational study analyzing the hematological evaluation blood counts and immunophenotyping of TCD3 + , TCD4 + , TCD8 + , B, and natural killer (NK) cells of the peripheral blood in 79 low-risk pregnant women and of 30 control women from the state of Pernambuco, Brazil, was performed. RESULTS: No significant differences were detected between the hematological profiles of the 2nd and 3rd trimesters. Nevertheless, the median level of B cells decreased significantly in the 2nd (174 × 103 µL; p < 0.002) and 3rd trimesters (160 × 103 µL; p < 0.001), compared with the control group (296 × 103 µL). Similarly, the median level of NK cells was lower in the 2nd (134 × 103 µL; p < 0.0004) and 3rd trimesters (100 × 103 µL, p < 0.0004), compared with the control group (183 × 103 µL). In contrast, relative TCD4+ and TCD8+ levels increased in the 2nd and 3rd trimesters compared with the controls (TCD4 + : 2nd trimester = 59%; p < 0.001; 3rd trimester = 57%; p < 0.01; control = 50%; and TCD8 + : 2nd trimester = 31%; p < 0.001; 3rd trimester = 36%; p < 0.01; control = 24%). CONCLUSION: Low-risk pregnant women have ∼ 40% less B and NK cells in the peripheral blood, compared with non-pregnant women. These parameters may improve health assistance for mothers and contribute to define reference values for normal pregnancies.

OBJETIVO: Descrever o intervalo de referência imunológico e hematológico de gestantes de baixo risco. MéTODOS: Realizou-se uma análise retrospectiva, de um estudo básico e translacional, analisando o perfil hematológico e a imunofenotipagem das células TCD3 + , TCD4 + , TCD8 + , B e natural killer (NK) do sangue periférico de 79 gestantes de baixo risco e de 30 mulheres (controles) do estado de Pernambuco, Brasil. RESULTADOS: Não observamos diferenças significativas entre os perfis hematológicos do 2° e 3° trimestres. No entanto, houve redução das células B no 2° (média = 174 × 103 µL; p < 0,002) e no 3° trimestres (160 × 103 µL; p < 0,001), comparado com o grupo controle (296 × 103 µL). A mediana das células NK foi menor no 2° (134 × 103 µL; p < 0,0004) e no 3° trimestres (100 × 103 µL; p < 0,0004), comparado com o grupo controle (183 × 103 µL). Porém, o percentual de TCD4+ e de TCD8+ aumentou no 2° e 3° trimestres em relação aos controles (TCD4 + : 2° trimestre = 59%; p < 0,001; 3° trimestre = 57%; p < 0,01; controle = 50%; e TCD8 + : 2° trimestre = 31%; p < 0,001; 3° trimestre = 36%; p < 0,01; controle = 24%). CONCLUSãO: Mulheres grávidas de baixo risco têm ∼ 40% menos células B e NK no sangue periférico em comparação com mulheres não grávidas. Estes parâmetros podem melhorar a assistência à saúde das mães e contribuir para a definição de valores de referência para gestações normais.

Is oxidized low-density lipoprotein the connection between atherosclerosis, cardiovascular risk and nephrolithiasis?

Nephrolithiasis is considered a systemic disease. A link has been established between nephrolithiasis, cardiovascular disease (CVD), the metabolic syndrome and atherosclerosis. A significant correlation has been found between the high levels of oxidized low-density lipoprotein (oxLDL) and CVD and atherosclerosis, including coronary and femoral artery disease. To the best of our knowledge, oxLDL has not been evaluated in patients with nephrolithiasis. This study aimed to evaluate serum levels of oxLDL, anti-oxLDL antibodies (oxLDL-ab) and other markers of atherosclerosis in patients with nephrolithiasis, according to the severity of the disease. The population sample consisted of 94 patients of 30-70 years of age with no symptoms of CVD who presented with renal calculi documented by ultrasonography, abdominal X-ray or computed tomography. The patients were divided into two groups: Group 1 (≥ 3 stones) and Group 2 (1-2 stones). A comparison control group was formed with 21 healthy individuals. Enzyme-linked immunosorbent assays were used to assess oxLDL and oxLDL-ab. Lipid peroxidation indexes were also analyzed. Median serum oxLDL values were higher in Groups 1 and 2 compared to the control group (≥ 3 stones, p = 0.02; 1-2 stones, p = 0.03). Median serum anti-oxLDL antibody levels were lower in the patients in Group 1 compared to the controls (p = 0.03). There was no significant difference in the oxLDL/oxLDL-ab ratio between patients and controls. These findings suggest that this may be the link between nephrolithiasis and the greater incidence of atherosclerosis and cardiovascular disease in patients with kidney stones.

Chemokines in pregnant women with sickle cell disease.

Pregnancy in sickle cell disease is a problem due to the adverse outcomes related to the disease. Research into the role of chemokines in sickle cell disease is available, but studies investigating the disease in pregnancy are scarce. Our data show the chemokine profiles of pregnant women with sickle cell disease compared with control groups. There were no differences in MCP-1 level among the groups, but IL-8 and MIG were likely related with disease activity. In addition, levels of IP-10 were higher in pregnant women with sickle cell disease and, interestingly, RANTES levels were higher in normal pregnancy when compared to pregnancy in sickle cell disease. More studies should be encouraged to fully elucidate chemokine activity during pregnancy in sickle cell disease.

Could enzyme replacement therapy promote immune tolerance in Gaucher disease type 1?

Among the lysosomal storage disorders, Gaucher disease (GD) features some of the most striking alterations in the immune system, including increased levels of cytokines and chemokines. Although studies have demonstrated the efficacy of enzyme replacement therapy (ERT) for GD, the ideal dosage remains controversial. In this study, we report differences in levels of cytokines (IL-6, TNF-a, and IFN-y) and chemokines (IL-8, IP-10, and MCP-1) in patients with GD type 1 treated with different ERT dosages and treatment durations. Patients were recruited from two ERT centers in Brazil and divided into two groups according to treatment facility. Comparison between groups showed that patients in group 1 had received ERT for longer (p=0.0078) and at higher doses (p=0.0002) than those in group 2. Patients in group 1 exhibited decreased levels of IL-6 (p=0.0006), TNF-α (p<0.0001), IFN-γ (p<0.0001), IL-8 (p=0.0083), IP-10 (p<0.0001), and MCP-1 (p<0.0001) when compared to patients in group 2. Otherwise, patients in both groups were clinically similar, with no differences in hemoglobin, platelet, or leukocyte counts. Our data suggest that in GD type 1 the dosage and duration of therapy may be associated with establishment of peripheral tolerance and, consequently, decreased serum levels of inflammatory cytokines and chemokines.

High Levels of CXCL8 and Low Levels of CXCL9 and CXCL10 in Women with Maternal RhD Alloimmunization.

Maternal RhD alloimmunization is an inflammatory response against protein antigens in fetal red blood cells (RBC). However, not all women become alloimmunized when exposed to RhD+ fetal RBC. Thus, this study aimed to evaluate levels of inflammatory chemokines in RhD- pregnant women with erythrocyte alloimmunization. CXCL8, CXCL9, CCL5, and CXCL10 levels were determined from cell culture supernatants by flow cytometry in 46 (30 non-alloimmunized RhD- and 16 previously alloimmunized RhD-) pregnant women. CXCL8 levels were significantly higher (P < 0.004), and CXCL9 (P < 0.008) and CXCL10 (P < 0.003) levels were significantly lower in alloimmunized pregnant women. No significant difference in CCL5 levels was detected between the groups. Fetal RHD genotyping was performed in the alloimmunized RhD- group by real-time PCR. Anti-D alloantibody was detected in 10 mothers and anti-D and -C in six mothers. Twelve fetuses were RHD positive and four were RHD negative. Further studies of serum chemokines and placenta tissue could provide a better understanding of the cells involved in the pathogenesis of maternal erythrocyte alloimmunization.

The balance between the serum levels of IL-6 and IL-10 cytokines discriminates mild and severe acute pneumonia.

BACKGROUND: To identify markers for earlier diagnosis of severe pneumonia, we assess the correlation between serum cytokine profile of children with different pneumonia severity. METHODS: In 25 hospitalized children, 7 with mild pneumonia and 18 with severe pneumonia, the serum concentration of 11 cytokines in three sampling times were dosed. Statistical analysis included parametric and non-parametric tests, Pearson correlation and ROC curve for cut-off definition of cytokines. RESULTS: At admission, IL-6 serum levels were high in mild or severe pneumonia, and was associated to vomiting (P = 0.019) in both groups; and also to dyspnea (P = 0.012) and white blood cell count (P = 0.045) in patients with severe pneumonia. IL-10 levels were also high in patients with pneumonia and were associated to lymphocytosis (P = 0.025). The ROC curve of the IL-6:IL-10 serum levels ratio discriminated severe pneumonia cases at admission, and persistence of infection in the third day of antibiotic therapy, with positive predictive values of 93% and 89%, respectively. CONCLUSIONS: The balance between IL-6 and IL-10 serum levels showed to be a more discriminative marker for severity definition and evaluation of recovery in patients with pneumonia.

CD4+CD25 high Foxp3+ Treg deficiency in a Brazilian patient with Gaucher disease and lupus nephritis.

Gaucher Disease (GD) is a rare autosomal recessive disorder caused by the deficient activity of beta-glucocerebrosidase. GD is one of the lysosomal storage diseases with the most remarkable alterations in the immune system, and that may manifest clinically as autoimmune disorders and malignancy. We reported the immunological evaluation of a patient with GD and lupus nephritis. Decreased absolute values of T, and NK, and an inversion of CD4(+)/CD8(+) ratio, low levels of IgM and normal B cells were found when compared to reference values in a Brazilian population. Absence ofCD4(+)CD25(high)Foxp3(+) Treg and high levels of total NKT, iNKT cells and CD8(+) iNKT subsets were also observed when compared to the healthy control and GD patient without lupus nephritis. Treg subset and CD8(+) iNKT abnormalities might be involved in severe lupus nephritis in a GD patient. We conclude by emphasizing the importance of the immunological evaluation on early diagnosis of autoimmunity contributing to reduce mortality and morbidity of these patients.