RESUMO
BACKGROUND: Group B Streptococcus (GBS) is the leading cause of neonatal morbidity and mortality in developed countries. This study aims primarily to estimate the prevalence of maternal GBS positivity and secondarily to evaluate the compliance and the effectiveness of the current GBS prevention protocol. METHODS: This retrospective study has considered 27382 single pregnancies carried to delivery between 2001 and 2014 at our Obstetrics and Gynecology clinic. All women carrying a singleton pregnancy in the considered period were eligible to be included in this study. RESULTS: The GBS swab was positive in 17.66% of cases, negative in 51.93%, and unknown in 30.41%. Data collected revealed that out of the total of GBS-positive women, 3362 were treated with antibiotic prophylaxis, and 1331 were not. There were no differences between cases admitted to Neonatal Intensive Care Unit and perinatal deaths between treated and non-treated GBS-positive pregnancies. Moreover, the data showed that 74.62% of patients between 34 and 37 weeks of gestation at the time of delivery were treated with antibiotic prophylaxis unnecessarily, and 25.38% of patients >37 weeks of gestation whose GBS status at delivery was unknown would have required intrapartum antibiotic prophylaxis. The only risk factor for chorioamnionitis among GBS-positive women in multivariate logistic regression analysis was an early gestational age (OR 0.61; 95% CI: 0.56-0.66; P<0.05). CONCLUSIONS: GBS prevalence was found to be 17.66%, and prophylaxis in colonized patients was carried out correctly according to our internal procedure allowing a low incidence of adverse outcomes. Finally, the only risk factor associated with chorioamnionitis in GBS patients was early gestational age at delivery.
Assuntos
Corioamnionite , Doenças do Recém-Nascido , Complicações Infecciosas na Gravidez , Infecções Estreptocócicas , Gravidez , Recém-Nascido , Humanos , Feminino , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/prevenção & controle , Estudos Retrospectivos , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/prevenção & controle , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Streptococcus agalactiae , Doenças do Recém-Nascido/epidemiologia , Doenças do Recém-Nascido/prevenção & controleRESUMO
Glutaric aciduria type II (GA II) is a genetic disorder that interferes with the body's ability to break down proteins and fats in order to produce energy. Signs and symptoms vary greatly depending on the age of onset and severity of the condition. Pregnancy may be a high risk period in women affected by metabolic disorders, because the mother has to guarantee wellness for both her and fetus. A 37-years-old primigravida woman affected by a mild form of GA II presented to our high risk department. During pregnancy a dietician strictly controlled her diet and nutritional intake. The fetal growth was regular but around the 38th week a polyhydramnios was diagnosed. A modification in carbohydrate intake led to a normal amniotic fluid. Considering the high risk of metabolic decompensation during labor, an elective cesarean section was programmed. The rare disease geneticist gave some indications to follow before, during and after delivery to reduce the risk for the mother. No complications occurred and the patient with her baby was discharged on the third postoperative day. We present a case report and a review of literature. In pregnant women affected by GA II periodical nutritional and obstetrical evaluations are important to monitor maternal condition and fetal growth. Adequate nutrient intake is fundamental to preserve mother and fetus from complications. Elective caesarean section is preferred to reduce metabolic distress during delivery and to avoid the risk of metabolic crisis. Pregnant women with metabolic diseases are increasing, consequently guidelines may be necessary for a better management.
RESUMO
SARS-CoV-2 disease mechanisms are not yet fully understood, especially in cases affecting pregnant women. In fact, although they suffer from the same symptoms as non-pregnant women, they are more susceptible to adverse outcomes of COVID-19 as well as pregnancy complications leading to stillbirth, premature rupture of membrane, or intrauterine fetal demise (IUFD). The consequences on pregnancy are not clearly correlated with the severity of the infection. We present a case of fetal death in a 30-year-old woman with a confirmed SARS-CoV-2 infection without any other significant clinical or obstetric disorders. A histopathological examination of the placenta indicated massive and diffuse intervillar fibrinoid deposits associated with chronic histiocytic intervillositis that can be associated with SARS-CoV-2 placentitis. Given the high rates of SARS-CoV-2 infections in pregnancy, it is important to understand the factors that determine negative pregnancy outcomes, regardless of the severity of the patient's symptoms.
RESUMO
Inflammatory bowel disease (IBD) is a chronic and progressive inflammatory condition of the gastrointestinal tract. Although the causative events that lead to the onset of IBD are yet to be fully elucidated, deregulation of immune and inflammatory mechanisms are hypothesized to significantly contribute to this disorder. Since the onset of IBD is often during infancy, in the present study, the serum values of a large panel of cytokines and chemokines in pediatric patients (<18 years; n=26) were compared with age-matched controls (n=37). While elevations in the serum level of several proinflammatory and immune regulating cytokines were confirmed, such as interleukin (IL)-1ß, IL-5, IL-7, interferon (IFN)-γ-inducible protein-10, IL-16, cutaneous T-cell-attracting chemokine, leukemia inhibitory factor, monokine induced by γ-IFN, IFN-α2 and IFN-γ, notably decreased levels of IL-2, IL-17 and macrophage inhibitory protein-1ß were also observed. Therefore, while a number of proinflammatory cytokines exhibit increased levels in IBD patients, pediatric IBD patients may also exhibit certain aspects of a reduced immunological response.
RESUMO
Curcumin belongs to the family of natural compounds collectively called curcuminoids and it possesses remarkable beneficial anti-oxidant, anti-inflammatory, anti-cancer, and neuroprotective properties. Moreover it is commonly assumed that curcumin has also been suggested as a remedy for digestive diseases such as inflammatory bowel diseases (IBD), a chronic immune disorder affecting the gastrointestinal tract and that can be divided in two major subgroups: Crohn's disease (CD) and Ulcerative Colitis (UC), depending mainly on the intestine tract affected by the inflammatory events. The chronic and intermittent nature of IBD imposes, where applicable, long-term treatments conducted in most of the cases combining different types of drugs. In more severe cases and where there has been no good response to the drugs, a surgery therapy is carried out. Currently, IBD-pharmacological treatments are generally not curative and often present serious side effects; for this reason, being known the relationship between nutrition and IBD, it is worthy of interesting the study and the development of new dietary strategy. The curcumin principal mechanism is the suppression of IBD inflammatory compounds (NF-κB) modulating immune response. This review summarizes literature data of curcumin as anti-inflammatory and anti-oxidant in IBD, trying to understand the different effects in CD e UC.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Curcumina/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Química Farmacêutica , Ensaios Clínicos como Assunto , Curcumina/análogos & derivados , Curcumina/farmacologia , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/etiologia , Terapia de Alvo Molecular , Nanotecnologia , Resultado do TratamentoRESUMO
BACKGROUND: Chlamydia trachomatis interaction with HR-HPV types has highlighted a central role in cervical cancer development. The aim of this study was to investigate HPV prevalence and genotypes distribution in women at risk for C. trachomatis infection and negative for intraepithelial lesion or malignancy. METHODS: 1071 cervical swabs were tested for C. trachomatis by Real Time PCR and genotyping by ompA gene sequencing. Additionally, a quantitative Real time-PCR was performed to assess the expression of the C. trachomatis Hsp60-encoding gene (Ct604 portion), linked to a persistent status of infection. HPV infection and genotypes was investigated in C. trachomatis positive women using Luminex technology. RESULTS: C. trachomatis infection was detected in 53 out of 1071 (4.5%) samples, of which the 53% resulted positive for Hsp60 gene expression. The overall prevalence of HPV infection in C. trachomatis positive samples was of 60.4% (32/53): in 37.5% of samples was present a single genotype, while multiple genotypes infections were found in the 62.5% of them. Among women with a C. trachomatis chronic infection, 68% were HPV co-infected and the 79% showed multiple genotypes. Should be noted that levels of C. trachomatis Hsp60 expression in HPV co-infected women were significantly lower compared to women infected only with C. trachomatis. The C. trachomatis serotype F was found in the majority of samples, independently of HPV infection. CONCLUSIONS: A high prevalence of HPV multiple infections have been found in young women affected with a C. trachomatis chronic infection. These observations suggested that the expression of CHSP60-1, interfering with both apoptotic and cellular senescence pathways, may promote a favourable local microenvironment for HPV infection.
RESUMO
Mevalonate Kinase Deficiency (MKD) is a rare autosomal recessive inborn disorder of cholesterol biosynthesis caused by mutations in the mevalonate kinase (MK) gene, leading to MK enzyme decreased activity. The consequent shortage of mevalonate-derived isoprenoid compounds results in an inflammatory phenotype, caused by the activation of the NALP3 inflammasome that determines an increased caspase-1 activation and IL-1 ß release. In MKD, febrile temperature can further decrease the residual MK activity, leading to mevalonate pathway modulation and to possible disease worsening. We previously demonstrated that the administration of exogenous isoprenoids such as geraniol or the modulation of the enzymatic pathway with drugs, such as Tipifarnib, partially rescues the inflammatory phenotype associated with the defective mevalonic pathway. However, it has not been investigated yet how temperature can affect the success of these treatments. Thus, we investigated the effect of temperature on primary human monocytes from MKD patients. Furthermore the ability of geraniol and Tipifarnib to reduce the abnormal inflammatory response, already described at physiological temperature in MKD, was studied in a febrile condition. We evidenced the role of temperature in the modulation of the inflammatory events and suggested strongly considering this variable in future researches aimed at finding a treatment for MKD.
Assuntos
Deficiência de Mevalonato Quinase/tratamento farmacológico , Quinolonas/uso terapêutico , Temperatura , Terpenos/uso terapêutico , Monoterpenos Acíclicos , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Vias Biossintéticas/efeitos dos fármacos , Proteínas de Transporte/metabolismo , Criança , Citocinas/sangue , Feminino , Humanos , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Deficiência de Mevalonato Quinase/sangue , Ácido Mevalônico/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR , Quinolonas/farmacologia , Terpenos/farmacologiaRESUMO
Since contradictory findings have been reported on potential effects of statins in modulating the inflammatory response, we have analysed the biological activity of lovastatin both in vitro using the Raw 264.7 murine macrophagic cell line and in vivo using BALB/c mice. When added to Raw 264.7 cells in combination with lipopolysaccharide, lovastatin significantly potentiated the release of interleukin-1ß, interleukin-6 and interleukin-12 with respect to lipopolysaccharide alone and showed an additive effect on the release of nitric oxide. Similarly, when lovastatin was intraperitoneally administrated to BALB/c mice, it did not induce any pro-inflammatory effect when used alone, but it significantly potentiated the pro-inflammatory activity of lipopolysaccharide, in terms of number of intraperitoneal cells and serum levels of serum amyloid A, interleukin-1ß, interleukin-6 and interleukin-12. A potential clinical implication of our study is that lovastatin might exert a pro-inflammatory activity in subjects affected by inflammatory processes, with clinically evident or subclinical infections.
Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/toxicidade , Mediadores da Inflamação/metabolismo , Inflamação/induzido quimicamente , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Animais , Linhagem Celular , Colesterol/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Inflamação/imunologia , Inflamação/metabolismo , Interleucina-12/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/metabolismo , Proteína Amiloide A Sérica/metabolismo , Fatores de TempoRESUMO
BACKGROUND: Mevalonate kinase deficiency (MKD) is a rare genetic autoinflammatory disease caused by blocking of the enzyme mevalonate kinase in the pathway of cholesterol and isoprenoids. The pathogenic mechanism originating an immune response in MKD patients has not been clearly understood. METHODS: We investigated the dysregulation of expression of selected cytokines and chemokines in the serum of MKD patients. The results have been compared with those observed in an MKD mouse model obtained by treating the mice with aminobisphosphonate, a molecule that is able to inhibit the cholesterol pathway, mimicking the genetic block characteristic of the disease. RESULTS: Interleukin (IL)-1ß, IL-5, IL-6, IL-9, IL-17, granulocyte colony-stimulating factor, monocyte chemotactic protein-1, tumor necrosis factor-α, and IL-4 expression were dysregulated in sera from MKD patients and mice. Moreover, geraniol, an exogenous isoprenoid, when administered to MKD mice, restored cytokines and chemokines levels with values similar to those of untreated mice. CONCLUSION: Our findings, which were obtained in patients and a mouse model mimicking the human disease, suggest that these cytokines and chemokines could be MKD specific and that isoprenoids could be considered as potential therapeutic molecules. The mouse model, even if with some limitations, was robust and suitable for routine testing of potential MKD drugs.
Assuntos
Quimiocinas/sangue , Citocinas/sangue , Modelos Animais de Doenças , Regulação da Expressão Gênica/imunologia , Deficiência de Mevalonato Quinase/imunologia , Monoterpenos Acíclicos , Animais , Difosfonatos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Especificidade da Espécie , TerpenosRESUMO
Growing knowledge about the cytokine network response has led to a better comprehension of mechanisms of pathologies and to the development of new treatments with biological drugs, able to block specific molecules of the immune response. Indeed, when the cytokine production is deregulated, diseases often occur. The understanding of the physiological mechanism of the cytokine network would be useful to better comprehend pathological conditions. Moreover, since the immune system and response change their properties with development, differences in patients' age should be taken into account, both in physiological and in pathological conditions. In this study, we analyzed the profile of 48 cytokines and chemokines in the serum of healthy subjects, comparing adults (≥18 years) with young children and children (1-6 and 7-17 years). We found that a certain number of cytokines were not being produced in healthy subjects; others showed a constant serum level amongst the groups. Certain cytokines exhibited a downward or an upward trend with increasing age. The remaining cytokines were up- or downregulated in the group of the children with respect to the other groups. In conclusion, we drew some kinds of guidelines about the physiological production of cytokines and chemokines, underling the difference caused by aging.
Assuntos
Citocinas/sangue , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Interferon-alfa/sangue , Interleucina-12/sangue , Interleucina-15/sangue , Interleucina-1alfa/sangue , Interleucina-1beta/sangue , Interleucina-3/sangue , Interleucina-5/sangue , Fator Inibidor de Leucemia/sangue , Linfotoxina-alfa/sangue , MasculinoAssuntos
Colite Ulcerativa/epidemiologia , Doença de Crohn/epidemiologia , Feminino , Humanos , MasculinoRESUMO
The knowledge of the human genome is in continuous progression: a large number of databases have been developed to make meaningful connections among worldwide scientific discoveries. This paper reviews bioinformatics resources and database tools specialized in disseminating information regarding genetic disorders. The databases described are useful for managing sample sequences, gene expression and post-transcriptional regulation. In relation to data sets available from genome-wide association studies, we describe databases that could be the starting point for developing studies in the field of complex diseases, particularly those in which the causal genes are difficult to identify.
Assuntos
Bases de Dados Genéticas , Doenças Genéticas Inatas/genética , Genoma Humano , Biologia Computacional , Genômica , HumanosRESUMO
DC-SIGN and L-SIGN are receptors expressed on specialized macrophages in decidua, (Hofbauer and placental capillary endothelial cells), known to interact with several pathogens, including HIV-1. To disclose the possible involvement of these molecules in the susceptibility to HIV vertical transmission, we analyzed DC-SIGN and L-SIGN gene single nucleotide polymorphisms (SNPs) in 192 HIV-1 positive children and 58 HIV-1 negative children all born to HIV-1 positive mothers, as well as 96 healthy uninfected children not exposed to HIV-1, all from Northeast Brazil. The frequency of three SNPs in the DC-SIGN promoter (-139G>A, -201G>T and -336A>G) were significantly different when comparing HIV positive children with HIV-1 exposed uninfected children, indicating an association with susceptibility to HIV-1 vertical transmission. This genetic association suggests that DC-SIGN molecule may play a role in susceptibility to HIV-1 infection through vertical transmission.
Assuntos
Moléculas de Adesão Celular/genética , Infecções por HIV/genética , Infecções por HIV/transmissão , HIV-1 , Transmissão Vertical de Doenças Infecciosas , Lectinas Tipo C/genética , Polimorfismo de Nucleotídeo Único , Receptores de Superfície Celular/genética , Alelos , Brasil , Criança , Pré-Escolar , Éxons , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Regiões Promotoras Genéticas , Sequências de Repetição em TandemRESUMO
BACKGROUND: A potential anti-inflammatory effect of clodronate--an aminobisphosphonate--was described to antagonize the pro-inflammatory effects of the block in the mevalonate pathway, the main feature of a rare auto-inflammatory disease called mevalonate kinase deficiency (MKD). OBJECTIVE: In this study we evaluated the potential anti-inflammatory effect of clodronate in MKD--a still orphan drug pediatric disease. METHODS: We studied some biological parameters, nitric oxide production using Griess reagents and programmed cell death by flow cytometry, as common inflammatory parameters in MKD, in the presence of different doses of clodronate (1, 10 and 100 µM). RESULTS: In our cellular model and in monocytes from patients with MKD, clodronate induced an increase in programed cell death and nitric oxide production in comparison with non-treated cells. CONCLUSION: Our findings suggest that clodronate does not have an anti-inflammatory effect as previously reported but that it increases the epiphenomena of this pediatric disease.
Assuntos
Anti-Inflamatórios/farmacologia , Ácido Clodrônico/farmacologia , Deficiência de Mevalonato Quinase , Modelos Biológicos , Monócitos/efeitos dos fármacos , Adolescente , Adulto , Alendronato , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Células Cultivadas , Criança , Feminino , Humanos , Inflamação/induzido quimicamente , Lipopolissacarídeos , Masculino , Camundongos , Óxido Nítrico/metabolismo , Adulto JovemRESUMO
Mevalonic aciduria (MA), the most severe form of mevalonate kinase deficiency (MKD), is still an orphan drug disease and the pathogenetic mechanisms underlying neuronal dysfunction is still poorly understood. In our study we have investigated the apoptotic mechanism mediated by the exposure of the cultured neuroblastoma cell line, SH-SY5Y, to lovastatin in absence or in presence of the isoprenoid, geranylgeraniol, with the aim of unraveling the pathogenesis of MA. Lovastatin, blocks the mevalonate pathway inhibiting the 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CR), an enzyme of the mevalonate pathway upstream the mevalonate kinase enzyme, reproducing biochemical features similar to those found in MKD. We demonstrate that apoptosis in neuronal lovastatin treated-cells is induced by the mitochondrial pathway, with caspase-9 as the initiator and caspase-3 as the effector caspase. The presence of geranylgeraniol modulates both the caspase-9 and caspase-3 activity in a dose-dependent way, confirming that this isoprenoid enters the mevalonate pathway, is metabolized and finally is able to by-pass the statin biochemical block reconstituting the mevalonate pathway. According to our findings, it should not be the time course adopted that modulates the apoptotic response but rather the isoprenoid itself. Being aware that our results have been obtained using a biochemical model of MKD, and not cells from patients with the disease, we believe our findings increase the knowledge of MA pathogenesis, and may possibly contribute to the development of novel therapeutic strategies.
Assuntos
Apoptose/efeitos dos fármacos , Diterpenos/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Lovastatina/farmacologia , Análise de Variância , Caspases/metabolismo , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Interações Medicamentosas , Humanos , Neuroblastoma/patologia , Fatores de TempoRESUMO
Cytokines/chemokines are involved in the immune response of infections, including HIV-1. We defined the profile of 48 cytokines/chemokines in cerebrospinal fluid from 18 cART patients with chronic HIV-1 infection by Luminex technology. Nine patients were affected with leukoencephalopathies: five with John Cunningham virus (JCV) + progressive multifocal leukoencephalopathy (PML) and four with JCV-not determined leukoencephalopathy (NDLE). In addition, nine HIV-1-positive patients with no neurological signs (NND) and five HIV-1-negative patients affected with acute disseminated encephalomyelitis (ADEM) were enrolled. Ten cytokines (IL-15, IL-3, IL-16, IL-18, CTACK, GRO1, SCF, MCP-1, MIF, SDF) were highly expressed in HIV-1-positive patients while IL-1Ra and IL-17 were present at a lower level. In addition, the levels of IL-17, IL-9, FGF-basic, MIP-1ß, and MCP-1 were significantly higher (p < 0.05) in patients with neurological diseases (PML, NDLE, ADEM) with respect to NND. Focusing the attention to the cytokine profile in JCV + PML patients with respect to JCV-NDLE patients, only TNF-ß was significantly downregulated (p < 0.05) in JCV + PML patients. This pilot study emphasized the role of immunoregulation in HIV-1-related neurological disorders during cART treatment.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Citocinas/líquido cefalorraquidiano , Encefalomielite Aguda Disseminada/líquido cefalorraquidiano , Infecções por HIV/líquido cefalorraquidiano , HIV-1 , Leucoencefalopatia Multifocal Progressiva/líquido cefalorraquidiano , Adulto , Idoso , Citocinas/imunologia , Encefalomielite Aguda Disseminada/tratamento farmacológico , Encefalomielite Aguda Disseminada/imunologia , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Leucoencefalopatia Multifocal Progressiva/tratamento farmacológico , Leucoencefalopatia Multifocal Progressiva/imunologia , Leucoencefalopatia Multifocal Progressiva/virologia , Masculino , Pessoa de Meia-Idade , Projetos PilotoAssuntos
Regiões 5' não Traduzidas , Doenças Inflamatórias Intestinais/genética , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , beta-Defensinas/genética , Adulto , Peptídeos Catiônicos Antimicrobianos/metabolismo , Estudos de Casos e Controles , Colite Ulcerativa/genética , Doença de Crohn/genética , Feminino , Predisposição Genética para Doença/genética , Haplótipos , Humanos , Masculino , beta-Defensinas/metabolismoRESUMO
Crohn's disease (CD) is a multifactorial disease, in which environmental, microbial and genetic factors play important roles. CD is characterized by a chronic granulomatous inflammation by necrotic scarring with aspects of full-thickness wall. In spite of affecting mainly young adults, sometimes, CD can be present in the first year of life (early onset Crohn disease, EOCD) showing an unpredictable course and being often more severe than at older ages. In this paper we propose the hypothesis that EOCD patients should be analyzed using a Mendelian approach with family studies aimed to identify new loci directly involved in the early onset Crohn's disease. So we will leave the classic association study approach used until now for the identification of genes responsible for susceptibility to CD and propose linkage family analysis as alternative and powerful tool for the identification of new genetic variants associated with familiar cases of EOCD.