ABSTRACT
Limited information is available about the effect of mid-pregnancy viral infections on the placental expression of efflux transporters and offspring behavior. We hypothesized that maternal exposure to polyinosinic-polycytidylic acid [poly(I:C)], a synthetic double-stranded RNA viral mimic, would impair placental cell turnover, the expression of selected ABC transporters and adult offspring behavior. C57BL/6 mice were administered poly(I:C) (10 mg/Kg;ip) or vehicle at gestational day (GD) 13.5 (mid-pregnancy). Dams were euthanized for blood collection 4 h after injection, fetal and placental collection at GD18.5 or allowed to deliver spontaneously at term. At GD 13.5, poly(I:C) induced an acute pro-inflammatory response characterized by an increase in maternal plasma levels of IL-6, CXCL-1 and CCL-2/MCP-1. At GD 18.5, poly(I:C) decreased cell proliferation/death in the labyrinthine and increased cell death in the junctional zones, characterizing a disruption of placental cell turnover. Abca1 and Abcg1 immunolabelling was decreased in the labyrinthine zone, whereas Abca1, Abcg1 and breast cancer resistance transporter (Bcrp) expression increased in the junctional zone. Moreover, adult offspring showed motor and cognitive impairments in the Rotarod and T-water maze tests. These results indicate that viral infection during mid-pregnancy may disrupt relevant placental efflux transporters, as well as placental cell turnover and offspring behavior in adult life.
Subject(s)
ATP-Binding Cassette Transporters , Cognitive Dysfunction , ATP Binding Cassette Transporter, Subfamily G, Member 2/metabolism , ATP-Binding Cassette Transporters/metabolism , Animals , Cognitive Dysfunction/metabolism , Female , Membrane Transport Proteins/metabolism , Mice , Mice, Inbred C57BL , Neoplasm Proteins/metabolism , Placenta/metabolism , Poly I-C/pharmacology , PregnancyABSTRACT
Bacterial infection alters placental ABC transporters expression. These transporters provide fetal protection against circulating xenobiotics and environmental toxins present in maternal blood. We hypothesized that lipopolysaccharide (LPS-bacterial mimic) alters the yolk sac morphology and expression of key ABC transporters in a gestational-age dependent manner. Yolk sac samples from C57BL/6 mice were obtained at gestational ages (GD) 15.5 and GD18.5, 4 or 24 h after LPS exposure (150ug/kg; n = 8/group). Samples underwent morphometrical, qPCR and immunohistochemistry analysis. The volumetric proportions of the histological components of the yolk sac did not change in response to LPS. LPS increased Abcg2 expression at GD15.5, after 4 h of treatment (p < 0.05). No changes in Abca1, Abcb1a/b, Abcg1, Glut1, Snat1, Il-1ß, Ccl2 and Mif were observed. Il-6 and Cxcl1 were undetectable in the yolk sac throughout pregnancy. Abca1, breast cancer resistance protein (Bcrp, encoded by Abcg2) and P-glycoprotein (P-gp/ Abcb1a/b) were localized in the endodermal (uterine-facing) epithelium and to a lesser extent in the mesothelium (amnion-facing), whereas Abca1 was also localized to the endothelium of the yolk sac blood vessels. LPS increased the labeling area and intensity of Bcrp in the yolk sac's mesothelial cells at GD15.5 (4 h), whereas at GD18.5, the area of Bcrp labeling in the mesothelium (4 and 24 h) was decreased (p < 0.05). Bacterial infection has the potential to change yolk sac barrier function by affecting Bcrp and Abcg2 expression in a gestational-age dependent-manner. These changes may alter fetal exposure to xenobiotics and toxic substances present in the maternal circulation and in the uterine cavity.
Subject(s)
ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics , Lipopolysaccharides/pharmacology , Yolk Sac/drug effects , Animals , Female , Gestational Age , Mice, Inbred C57BL , Pregnancy , Yolk Sac/metabolismABSTRACT
This paper analyzes the diagnosis aid of the dosage of lactate in the cerebrospinal fluid (CSF) in infectious diseases of the central nervous system (CNS). We analyzed prospectively 130 samples of CSF of 116 patients with diagnoses of infectious processes in the CNS. The 130 samples of CSF were divided into five groups: 28 samples of the control group, 40 of bacterial meningitis, 22 of viral meningitis, 16 of fungal meningitis and 24 of patients presenting acquired immune deficiency syndrome (AIDS). The concentration of lactate in the CSF was elevated in the group of patients with bacterial meningitis (average = 46.2 mg/dL), fungal meningitis (average = 27.3 mg/dL) and in the AIDS group (average = 23.5 mg/dL). In the control group and viral meningitis group the lactate content in the CSF presented the reference rates according to the employed method. The lactate dosage in the CSF presented a negative correlation with glycorrhachia and positive correlation with the cellularity and total proteins of the CSF. We conclude that the lactate dosage in the CSF, although unspecific, helps to distinguish the infectious processes of the CNS.
Subject(s)
Acquired Immunodeficiency Syndrome/cerebrospinal fluid , Lactates/cerebrospinal fluid , Meningitis/cerebrospinal fluid , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Child , Child, Preschool , Female , Glucose/cerebrospinal fluid , Humans , Infant , Infant, Newborn , Male , Meningitis, Bacterial/cerebrospinal fluid , Meningitis, Fungal/cerebrospinal fluid , Meningitis, Viral/cerebrospinal fluid , Middle Aged , Prospective StudiesABSTRACT
Twenty-five non-Hodgkin's adult patients of a cohort studied for detection of neurologic involvement were evaluated on the cerebrospinal fluid (CSF) protein profile. CSF and serum were collected in the same occasion. Blood-brain barrier and local synthesis of IgG were studied. There was an incidence of neurologic signs and symptoms in 48% of all patients. Samples analysis showed: increase of total protein in CSF in 52%; local synthesis of IgG in one HIV seropositive patient; IgG concentration increase in the CSF in the absence of malignant cells in the CSF in two patients that clinically improved after chemotherapy; oligoclonal bands only in the CSF in one HTLV-I seropositive patient. These data show that the study of CSF protein profile can contribute in the characterization of CNS involvement in non-Hodgkin lymphoma.
Subject(s)
Cerebrospinal Fluid Proteins/analysis , Immunoglobulin G/blood , Lymphoma, Non-Hodgkin/cerebrospinal fluid , Serum Albumin/analysis , Adult , Humans , Lymphoma, Non-Hodgkin/blood , Lymphoma, Non-Hodgkin/complications , Nephelometry and TurbidimetryABSTRACT
In an eight years time period (July 1984-June 1992) CSF samples of 40718 patients were studied, and 610 were from patients with AIDS clinically diagnosed and immunologically confirmed through HIV antibodies detection. Among opportunistic infections detected in them 85 were CNS cryptococcosis. For the purpose of this study the CSF of these 85 patients are the AIDS group of CNS cryptococcosis. For comparison, CSF data from 50 patients with CNS cryptococcosis but without AIDS were taken (non-AIDS group); in this group, 22 patients were immunosuppressed after renal transplant. In AIDS group, the more frequent CSF findings were: yeast presence at direct exam (Fuchs-Rosenthal cell counting chamber), growing of the yeast in cultures, and gamma globulins increase. In non-AIDS group were more frequent: hypercytosis, neutrophil cells presence, and total protein increase. Differences between the two groups are discussed taking into account CNS/CSF immune changes induced by HIV infection. It is concluded that in CNS cryptococcosis of patients with AIDS the CSF evidenced more extensive signs of the fungal opportunistic infection than signs of inflammatory response to the infection. The latter were more prominent among patients of the non-AIDS group of CNS cryptococcosis.
Subject(s)
Acquired Immunodeficiency Syndrome/cerebrospinal fluid , Brain Diseases/cerebrospinal fluid , Cryptococcosis/cerebrospinal fluid , Acquired Immunodeficiency Syndrome/complications , Adolescent , Adult , Aged , Brain Diseases/complications , Child , Cryptococcosis/complications , Female , Humans , Kidney Transplantation , Male , Middle AgedABSTRACT
Foi estudado o LCR de 85 pacientes com AIDS e criptococose do SNC. O diagnóstico clínico e imunológico de AIDS foi previamente estabelecido em todos os casos. Os resultados foram comparado aos de grupo de 50 pacientes com neurocriptococose porém sem AIDS (grupo näo-AIDS). Neste grupo 22 pacientes eram imunossuprimidos após transplante renal. Nos pacientes do grupo AIDS predominavam no LCR: detecçäo da levedura no exame direto (câmara de Fuchs-Rosenthal de contagem de células), culturas de levedura positivas e aumento do teor de globulinas gama. No grupo näo-AIDS predominavam: pleocitose, presença de polinucleares neutrófilos e aumento da concentraçäo protética total. As diferenças encontrdas entre os dois grupos säo discutidas, salientando-se as modificaçöes imunes induzidas no SNC/LCR pelo HIV. Conclui-se que na neurocriptococose em pacientes com AIDS o LCR evidenciou mais a infecçäo pelo fungo que a resposta inflamatória à infecçäo. Esta última predominou no LCR de pacientes do grupo neurocriptococose näo-AIDS
Subject(s)
Humans , Male , Female , Child , Adolescent , Adult , Middle Aged , Cryptococcosis/cerebrospinal fluid , Central Nervous System Diseases/cerebrospinal fluid , Acquired Immunodeficiency Syndrome/cerebrospinal fluid , Kidney TransplantationABSTRACT
In a seven year time period (July 1984 to June 1991) were studied CSF samples of 36,216 new patients, 470 of them infected by HIV. Number of AIDS patients represents 1.30% of total cases examined in the laboratory during this time period. Normal CSF was observed in only 16 cases (3.4%). Associated pathologies occurred in 66% of cases. Opportunistic infections predominated among them (227 cases). Data support indication for CSF examination in HIV infected patients. This exam must be as complete as possible.
Subject(s)
AIDS-Related Opportunistic Infections/cerebrospinal fluid , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle AgedABSTRACT
Durante o período de 7 anos (Julho 1984 a Junho 1991) foram estudados em laboratório de LCR 36.216 novos pacientes, 470 com AIDS. O número de pacientes com AIDS representa 1,30% de todos os casos novos no período; para os primeiros 6 meses de 1991 esse número atingiu 2,8%. LCR normal foi observado apenas em 16 casos (3,4%). Patologias associadas foram observadas em 66% dos casos. Infecçöes oportunistas predominaram entre elas (227 casos). Esses dados justificam indicar o exame de LCR em pacientes infectados pelo HIV, devendo o exame ser o mais completo possível
Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Adult , Middle Aged , Opportunistic Infections/cerebrospinal fluid , Acquired Immunodeficiency Syndrome/cerebrospinal fluid , Opportunistic Infections/complications , Acquired Immunodeficiency Syndrome/complicationsABSTRACT
HTLV-1 antibodies were investigated in serum and in CSF of 150 patients with neurologic disorders mainly myelopathies. The patients were considered into three groups according to the possible relationship of their disease to the presence of HTLV-1 antibodies: no relationship risk (control group), occasional risk group, and possible risk group. In this latter are 56 patients with crural spastic paraparesis or paraplegia of unknown etiology (SP). HTLV-1 antibodies were tested by the passive particle-agglutination method for anti-ATLA antibody detection. The search was negative in all patients of the control group, and positive (serum and/or CSF) in 16.5% of the patients from the second group and in 55.4% of the SP patients group. Clinical patterns in SP cases with HTLV-1 antibodies were those of tropical spastic paraparesis (TSP). CSF patterns considered (cytology, protein content and gamma-globulins rate) were different between TSP group with HTLV-1 antibodies in CSF and SP group with no HTLV-1 antibodies detection either in serum or in CSF. The difference was significant. Results of this investigation confirm the high incidence of TSP in Brazil, and bring additional indication for searching HTLV-1 antibodies in the CSF.
Subject(s)
HTLV-I Antibodies/analysis , Paraparesis, Tropical Spastic/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Brazil , Female , Humans , Male , Middle Aged , Paraparesis, Tropical Spastic/blood , Paraparesis, Tropical Spastic/cerebrospinal fluidABSTRACT
Foi pesquisada a presença de HTLV-1 anticorpos no soro e no LCR de 150 pacientes com afecçöes do sistema nervoso, particularmente mielopatias. Os pacientes foram considerados segundo três grupos, de acordo com a possível relaçäo entre a doença e a presença de HTLV-1 anticorpos: sem risco de relaçäo (grupo controle); grupo de risco ocasional; grupo de risco possível. Este último abrange 56 pacientes com paraparesia ou paraplegia crural espástica de etiologia näo esclarecida (PE). Foi utilizada para a pesquisa a técnica de aglutinaçäo passiva de partículas para anti-ATLA anticorpo, sendo obtidos os seguintes resultados: näo foram detectados HTLV-1 anticorpos no grupo controle e foram detectados (soro e/ou LCR) em 16,5% dos pacientes do segundo grupo e em 55,4% daqueles do terceiro grupo. O quadro clínico dos pacientes com PE e HTLV-1 anticorpos era compatível a paraparesia espática tropical (PET). Foi verificada diferença significativa quanto a dados do exame de LCR (citologia, concentraçäo proteica e teor de globulinas gama) ao se compararem os pacientes com PET com HTLV-1 anticorpos no LCR àqueles com PE em que tais anticorpos näo foram detectados nem no soro e nem no LCR. Os resultados deste estudo confirmam a elevada incidência da PET no Brasil e ilustram a necessidade da pesquisa desses anticorpos também no LCR
