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1.
BMC Med ; 21(1): 9, 2023 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-36600296

RESUMO

BACKGROUND: Understanding the relationship between chronic pain conditions and suicidal behavior-suicide attempt, other intentional self-harm, and death by suicide-is imperative for suicide prevention efforts. Although chronic pain conditions are associated with suicidal behaviors, these associations might be attributed to unmeasured confounding or mediated via pain comorbidity. METHODS: We linked a population-based Swedish twin study (N=17,148 twins) with 10 years of longitudinal, nationwide records of suicidal behavior from health and mortality registers through 2016. To investigate whether pain comorbidity versus specific pain conditions were more important for later suicidal behavior, we modeled a general factor of pain and two independent specific pain factors (measuring pain-related somatic symptoms and neck-shoulder pain, respectively) based on 9 self-reported chronic pain conditions. To examine whether the pain-suicidal behavior associations were attributable to familial confounding, we applied a co-twin control model. RESULTS: Individuals scoring one standard deviation above the mean on the general pain factor had a 51% higher risk of experiencing suicidal behavior (odds ratio (OR), 1.51; 95% confidence interval (CI), 1.34-1.72). The specific factor of somatic pain was also associated with increased risk for suicidal behavior (OR, 1.80; 95% CI, 1.45-2.22]). However, after adjustment for familial confounding, the associations were greatly attenuated and not statistically significant within monozygotic twin pairs (general pain factor OR, 0.89; 95% CI, 0.59-1.33; somatic pain factor OR, 1.02; 95% CI, 0.49-2.11) CONCLUSION: Clinicians might benefit from measuring not only specific types of pain, but also pain comorbidity; however, treating pain might not necessarily reduce future suicidal behavior, as the associations appeared attributable to familial confounding.


Assuntos
Dor Crônica , Dor Nociceptiva , Humanos , Ideação Suicida , Dor Crônica/epidemiologia , Estudos Longitudinais , Gêmeos Monozigóticos , Fatores de Risco , Doença Crônica
2.
Psychol Med ; 49(7): 1166-1173, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30221610

RESUMO

BACKGROUND: Most studies underline the contribution of heritable factors for psychiatric disorders. However, heritability estimates depend on the population under study, diagnostic instruments, and study designs that each has its inherent assumptions, strengths, and biases. We aim to test the homogeneity in heritability estimates between two powerful, and state of the art study designs for eight psychiatric disorders. METHODS: We assessed heritability based on data of Swedish siblings (N = 4 408 646 full and maternal half-siblings), and based on summary data of eight samples with measured genotypes (N = 125 533 cases and 208 215 controls). All data were based on standard diagnostic criteria. Eight psychiatric disorders were studied: (1) alcohol dependence (AD), (2) anorexia nervosa, (3) attention deficit/hyperactivity disorder (ADHD), (4) autism spectrum disorder, (5) bipolar disorder, (6) major depressive disorder, (7) obsessive-compulsive disorder (OCD), and (8) schizophrenia. RESULTS: Heritability estimates from sibling data varied from 0.30 for Major Depression to 0.80 for ADHD. The estimates based on the measured genotypes were lower, ranging from 0.10 for AD to 0.28 for OCD, but were significant, and correlated positively (0.19) with national sibling-based estimates. When removing OCD from the data the correlation increased to 0.50. CONCLUSIONS: Given the unique character of each study design, the convergent findings for these eight psychiatric conditions suggest that heritability estimates are robust across different methods. The findings also highlight large differences in genetic and environmental influences between psychiatric disorders, providing future directions for etiological psychiatric research.


Assuntos
Família/psicologia , Transtornos Mentais/genética , Transtornos Mentais/psicologia , Irmãos/psicologia , Adulto , Alcoolismo/genética , Alcoolismo/psicologia , Anorexia Nervosa/genética , Anorexia Nervosa/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/psicologia , Transtorno Bipolar/genética , Transtorno Bipolar/psicologia , Estudos de Casos e Controles , Estudos de Coortes , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/psicologia , Feminino , Interação Gene-Ambiente , Genótipo , Humanos , Masculino , Transtorno Obsessivo-Compulsivo/genética , Transtorno Obsessivo-Compulsivo/psicologia , Característica Quantitativa Herdável , Esquizofrenia/genética , Psicologia do Esquizofrênico , Suécia
3.
Mol Psychiatry ; 21(5): 717-21, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26303662

RESUMO

Recent studies have shown that different mental-health problems appear to be partly influenced by the same set of genes, which can be summarized by a general genetic factor. To date, such studies have relied on surveys of community-based samples, which could introduce potential biases. The goal of this study was to examine whether a general genetic factor would still emerge when based on a different ascertainment method with different biases from previous studies. We targeted all adults in Sweden (n=3 475 112) using national registers and identified those who had received one or more psychiatric diagnoses after seeking or being forced into mental health care. In order to examine the genetic versus environmental etiology of the general factor, we examined whether participants' full- or half-siblings had also received diagnoses. We focused on eight major psychiatric disorders based on the International Classification of Diseases, including schizophrenia, schizoaffective disorder, bipolar disorder, depression, anxiety, attention-deficit/hyperactivity disorder, alcohol use disorder and drug abuse. In addition, we included convictions of violent crimes. Multivariate analyses demonstrated that a general genetic factor influenced all disorders and convictions of violent crimes, accounting for between 10% (attention-deficit/hyperactivity disorder) and 36% (drug abuse) of the variance of the conditions. Thus, a general genetic factor of psychopathology emerges when based on both surveys as well as national registers, indicating that a set of pleiotropic genes influence a variety of psychiatric disorders.


Assuntos
Predisposição Genética para Doença , Transtornos Mentais/genética , Irmãos , Estudos de Coortes , Análise Fatorial , Humanos , Transtornos Mentais/epidemiologia , Análise Multivariada , Sistema de Registros , Suécia/epidemiologia
4.
Psychol Med ; 44(6): 1293-302, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23942194

RESUMO

BACKGROUND: Psychotic-like experiences (PLEs) and juvenile mania in adolescence index risk for severe psychopathology in adulthood. The importance of childhood problems with communication, reading, speech and mathematics for the development of PLEs and juvenile mania is not well understood. METHOD: Through the Child and Adolescent Twin Study in Sweden, we identified 5812 children. The parents were interviewed about their children's development at age 9 or 12 years. At age 15 or 18 years, children and parents completed questionnaires targeting current PLEs and juvenile mania symptoms. Logistic regressions were used to assess associations between problems with communication, reading, speech and mathematics and PLEs/juvenile mania symptoms. To evaluate the relative importance of genes and environment in these associations, we used bivariate twin analyses based on structural equation models. RESULTS: Children with parent-endorsed childhood problems with communication, reading and mathematics had an increased risk of developing auditory hallucinations and parental-reported juvenile mania symptoms in adolescence. The most consistent finding was that children with childhood problems with communication, reading and mathematics had an increased risk of developing auditory hallucinations [for example, the risk for self-reported auditory hallucinations at age 15 was increased by 96% for children with communication problems: OR (odds ratio) 1.96, 95% confidence interval (CI) 1.33-2.88]. The twin analyses showed that genetic effects accounted for the increased risk of PLEs and juvenile mania symptoms among children with communication problems. CONCLUSIONS: Childhood problems with communication, reading and mathematics predict PLEs and juvenile mania symptoms in adolescence. Similar to the case for schizophrenia and bipolar disorder, PLEs and juvenile mania may share genetic aetiological factors.


Assuntos
Transtorno Bipolar/epidemiologia , Transtornos da Comunicação/epidemiologia , Discalculia/epidemiologia , Dislexia/epidemiologia , Alucinações/epidemiologia , Transtornos Psicóticos/epidemiologia , Adolescente , Criança , Transtornos da Comunicação/genética , Comorbidade , Doenças em Gêmeos/epidemiologia , Doenças em Gêmeos/genética , Discalculia/genética , Dislexia/genética , Feminino , Alucinações/genética , Humanos , Masculino , Transtornos Psicóticos/genética , Suécia/epidemiologia
6.
Environ Sci Technol ; 48(12): 7143-50, 2014 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-24866381

RESUMO

Time-resolved emissions of particulate polycyclic aromatic hydrocarbons (PAHs) and total organic particulate matter (OA) from a wood log stove and an adjusted pellet stove were investigated with high-resolution time-of-flight aerosol mass spectrometry (AMS). The highest OA emissions were found during the addition of log wood on glowing embers, that is, slow burning pyrolysis conditions. These emissions contained about 1% PAHs (of OA). The highest PAH emissions were found during fast burning under hot air starved combustion conditions, in both stoves. In the latter case, PAHs contributed up to 40% of OA, likely due to thermal degradation of other condensable species. The distribution of PAHs was also shifted toward larger molecules in these emissions. AMS signals attributed to PAHs were found at molecular weights up to 600 Da. The vacuum aerodynamic size distribution was found to be bimodal with a smaller mode (Dva ∼ 200 nm) dominating under hot air starved combustion and a larger sized mode dominating under slow burning pyrolysis (Dva ∼ 600 nm). Simultaneous reduction of PAHs, OA and total particulate matter from residential biomass combustion may prove to be a challenge for environmental legislation efforts as these classes of emissions are elevated at different combustion conditions.


Assuntos
Aerossóis/análise , Poluentes Atmosféricos/análise , Biomassa , Temperatura Alta , Espectrometria de Massas/métodos , Material Particulado/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Carbono/análise , Culinária , Gases/análise , Compostos Orgânicos/análise , Tamanho da Partícula , Material Particulado/química , Hidrocarbonetos Policíclicos Aromáticos/química , Fatores de Tempo , Madeira/química
7.
Radiat Prot Dosimetry ; 195(3-4): 232-245, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34345904

RESUMO

This study compares dual-energy computed tomography (DECT) images of a phantom including different material inserts and with additional lateral titanium or stainless steel inserts, simulating bilateral hip prostheses. Dual-source (DS) and fast kV-switching (FKS) DECT with/without metal artefact reduction (MAR) were compared with regards to virtually monoenergetic CT number accuracy and the depiction of different materials. Streak artefacts were observed between the metal inserts that were more severe with steel compared to titanium inserts. The artefact severity and CT number accuracy depended on the photon energy (keV) for both DECT techniques. While MAR generally increased the CT number accuracy and material depiction within the streak artefacts, it sometimes decreased the accuracy outside the streak artefacts for both DS and FKS. FKS depicted the metal inserts more accurately than DS with regards to both CT numbers and external diameter.


Assuntos
Artefatos , Prótese de Quadril , Metais , Imagens de Fantasmas , Tomografia Computadorizada por Raios X
8.
Br J Anaesth ; 104(3): 305-12, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20150346

RESUMO

BACKGROUND: Major adverse cardiac events (MACEs) are a common cause of death after non-cardiac surgery. Despite evidence for the benefit of aspirin for secondary prevention, it is often discontinued in the perioperative period due to the risk of bleeding. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in order to compare the effect of low-dose aspirin with that of placebo on myocardial damage, cardiovascular, and bleeding complications in high-risk patients undergoing non-cardiac surgery. Aspirin (75 mg) or placebo was given 7 days before surgery and continued until the third postoperative day. Patients were followed up for 30 days after surgery. RESULTS: A total of 220 patients were enrolled, 109 patients received aspirin and 111 received placebo. Four patients (3.7%) in the aspirin group and 10 patients (9.0%) in the placebo group had elevated troponin T levels in the postoperative period (P=0.10). Twelve patients (5.4%) had an MACE during the first 30 postoperative days. Two of these patients (1.8%) were in the aspirin group and 10 patients (9.0%) were in the placebo group (P=0.02). Treatment with aspirin resulted in a 7.2% absolute risk reduction [95% confidence interval (CI), 1.3-13%] for postoperative MACE. The relative risk reduction was 80% (95% CI, 9.2-95%). Numbers needed to treat were 14 (95% CI, 7.6-78). No significant differences in bleeding complications were seen between the two groups. CONCLUSIONS: In high-risk patients undergoing non-cardiac surgery, perioperative aspirin reduced the risk of MACE without increasing bleeding complications. However, the study was not powered to evaluate bleeding complications.


Assuntos
Aspirina/administração & dosagem , Doenças Cardiovasculares/prevenção & controle , Assistência Perioperatória/métodos , Inibidores da Agregação Plaquetária/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Aspirina/efeitos adversos , Perda Sanguínea Cirúrgica , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/efeitos adversos , Hemorragia Pós-Operatória/induzido quimicamente
9.
Biochim Biophys Acta ; 1201(1): 51-4, 1994 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-7918582

RESUMO

The effect of 2.45 GHz microwave radiation on the permeability of unilamellar phosphatidylcholine liposomes has been studied. Leakage of 5(6)-carboxyfluorescein from the liposomes was measured using spectrofluorimetry after exposure to either microwaves or thermal heating for 5-20 min intervals. The exposure temperature, 37.6 +/- 0.5 degrees C, was well above the phase transition temperature of the lipid membrane. The microwave exposure did not result in any non-thermal increase in permeability above that produced by thermal heating. This study refutes the results reported by Saalman et al. [1] in which an increased liposome permeability due to microwave exposure was reported. The refined analysis in the present study shows that this increased liposome permeability was not a non-thermal microwave effect.


Assuntos
Lipossomos/efeitos da radiação , Micro-Ondas , Fluoresceínas , Temperatura Alta , Lipossomos/química , Permeabilidade , Segurança
10.
J Phys Chem B ; 109(33): 15775-9, 2005 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-16853002

RESUMO

Micellar solutions of tetramethylammonium dodecyl sulfate have been studied to determine the degree of counterion binding. Tetramethylammonium chloride was added over a wide range of surfactant concentrations such that the total concentration of tetramethylammonium ions in solution remained constant. Small angle neutron scattering experiments showed a constancy in aggregation number across this series, consistent with the constant C(aq) concept of Bales et al. (J. Phys. Chem. B 2001, 105, 6798). Pulsed-field gradient and electrophoretic NMR experiments were used to determine the degree of counterion dissociation, alpha, which was found to be 0.33. This value is in contrast to the value from conductivity measurements (alpha = 0.2), but supports the concept of an aggregation number based definition of alpha.


Assuntos
Espectroscopia de Ressonância Magnética , Nêutrons , Compostos de Amônio Quaternário/química , Dodecilsulfato de Sódio/química , Tensoativos/química , Espalhamento de Radiação
11.
J Med Eng Technol ; 39(2): 91-8, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25429800

RESUMO

Conventional skin UV-sensitivity phototesting is based on semi-quantitative assessment of minimal erythema dose (MED). This study demonstrates a method for quantitative MED determination, using a lengthwise attenuating UVB-field combined with tissue viability imaging (TiVi). The study aim was to investigate the agreement between MED acquired by traditional phototest and by the new method. Forty-seven voluntary subjects underwent phototesting with a traditional phototest and with the new technique. Test reading, carried out after 24 h, showed moderate agreement between the methods when assessed with TiVi (Kappa value=0.46) and visually (Kappa value=0.48). For the new method, no systematic differences were seen between outcomes assessed with TiVi or visually (95% CI for the mean difference=-1.6-2.0). In conclusion, the results give promising support for the concept of achieving a more precise MED estimation by combining continuous attenuating UV fields with new available bioengineering technology.


Assuntos
Diagnóstico por Imagem/instrumentação , Eritema/diagnóstico , Eritema/patologia , Pele/efeitos da radiação , Raios Ultravioleta , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenômenos Fisiológicos da Pele , Raios Ultravioleta/efeitos adversos , Adulto Jovem
12.
J Neuropathol Exp Neurol ; 57(12): 1138-45, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9862636

RESUMO

The first gene found to be amplified in human glioblastomas was EGFR at 7p12. More recently the MET gene at 7q31 was also reported amplified. We have studied chromosome 7 in a series of 47 glioblastomas by FISH, RFLP and microsatellite analysis. Four per cent (2/47) had 1 centromere, 26% (12/47) 2, 32% (15/47) 3, 4% (2/47) 4, and 34% (16/47) had subpopulations with variable numbers of chromosome 7 centromeres. In 25 of the 47 tumors (53%) the pattern of allelic imbalance observed at each informative locus was similar and in accord with the FISH data, indicating loss or gain of complete chromosome copies. In 32% of tumors (15/47) varying allelic imbalance was seen at different loci along the chromosome indicative of loss or gain of parts of chromosome 7 on a background of disomy, trisomy, tetrasomy, or polysomy. Amplification was studied in an extended series of 121 glioblastomas, and was seen at the 7p12 region in 47 tumors (39%). Forty-two tumors showed amplification of EGFR and 12 of these had extensive amplicons including a number of adjacent loci, always involving only 1 allele. The amplicons of 5 tumors (11%) did not include EGFR, indicating that other unidentified genes in the region are targeted for amplification. Amplification of MET was not found. The findings show that copy number changes of chromosome 7 are common and that a number of genes may be targeted for amplification at 7p12 in glioblastomas.


Assuntos
Cromossomos Humanos Par 7 , Rearranjo Gênico , Genes erbB-1 , Glioblastoma/genética , Receptores Proteína Tirosina Quinases/genética , Alelos , Centrômero/fisiologia , Cromossomos Humanos Par 8 , Humanos , Hibridização in Situ Fluorescente , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição
13.
J Neuropathol Exp Neurol ; 59(12): 1087-93, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11138928

RESUMO

Approximately 30%-35% of human glioblastomas have epidermal growth factor receptor (EGFR) gene amplification. Amplicons containing the EGFR gene frequently include several unidentified adjacent genes. Amplification of adjacent genes in the absence of EGFR amplification has been documented. To define the region in detail, we produced a YAC contig map, determining the orientation of the EGFR gene and the general order of 11 STS and EST markers. Seventy-six tumors with amplification of the region were found in a series of 246 human astrocytic gliomas. The amplicons showed amplification of contiguous or noncontiguous loci both telomeric and centromeric to the EGFR gene. Six percent (12/190) of the glioblastomas and 1 anaplastic astrocytomas had amplicons excluding the EGFR gene. These amplicons commonly contain amplified loci telomeric to the EGFR gene. Some of the amplified loci were found to be consistently overexpressed. The findings suggest that there may be other gene target(s) for amplification in the 7p12 region in addition to EGFR.


Assuntos
Astrocitoma/genética , Neoplasias do Sistema Nervoso Central/genética , Amplificação de Genes/genética , Mapeamento Cromossômico , Expressão Gênica , Frequência do Gene , Genes erbB-1/genética , Humanos
14.
J Neuropathol Exp Neurol ; 58(7): 697-701, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10411339

RESUMO

Amplification of the epidermal growth factor receptor (EGFR) occurs in about 40% of human glioblastomas. In half of these cases, rearrangements of the amplified gene result in aberrant transcripts and proteins. The most frequent rearrangement affects the external domain of the receptor and results in nonbinding of ligand and constitutive activity. Less frequent rearrangements involve changes resulting in the loss of cytoplasmic amino acid sequences necessary for downregulation of the receptor following ligand binding. Here we report the development and selection for a rearranged amplified EGF receptor, which lacks cytoplasmic amino acid sequences in a human glioblastoma xenograft. An identical aberration has previously been reported in glioblastoma tissue. The patient tumor material, as well as the first passages of the xenograft showed amplification of the EGFR gene, but no evidence of gene rearrangement or an aberrant transcript. Interphase FISH data show the amplified gene on double minutes. Between passages 3 and 16, the growth rate of the xenograft almost doubled, the rearranged amplicon became dominant, as did the aberrant transcript, indicating selection under these conditions.


Assuntos
Receptores ErbB/genética , Amplificação de Genes , Rearranjo Gênico , Glioblastoma/genética , Transplante de Neoplasias , Transplante Heterólogo , Animais , Sequência de Bases/genética , Amplificação de Genes/genética , Rearranjo Gênico/genética , Humanos , Hibridização in Situ Fluorescente , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
15.
Neurosci Biobehav Rev ; 21(4): 489-95, 1997 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9195607

RESUMO

Using highly sensitive analytical procedures, glutamate (Glu), aspartate (Asp) and several putative neurotransmitters and metabolites can be monitored simultaneously in the extracellular space of neostriatum, substantia nigra and cerebral cortex of the rat by in vivo microdialysis. Glu and Asp are found at sub-micromolar concentrations in all investigated brain regions. In order to ascertain their neuronal origin, we have extensively studied the sensitivity of extracellular Glu and Asp levels to: (i) K(+)-depolarization, (ii) Na(+)-channel blockade, (iii) removal of extracellular Ca2+, (iv) depletion of presynaptic vesicles, and (v) integrity of neuronal pathways. The relevance of these criteria for several neurotransmitters monitored simultaneously or in parallel experiments has also been examined. The functional interactions among different neuronal pathways in the basal ganglia are studied by using selective pharmacological treatments, administered systemically, or locally via intracerebral injections or the microdialysis perfusion medium. Immunohistochemical evidence for the existence of Glu and/or Asp neuronal pathways in the basal ganglia of the rat is presented, discussing especially new findings indicating the existence of a Glu-independent Asp system, intrinsic to the neostriatum of the rat. The clinical relevance of these interactions is discussed, focusing on the implications for the treatment of neurodegenerative disorders affecting the basal ganglia.


Assuntos
Ácido Aspártico/metabolismo , Gânglios da Base/metabolismo , Monoaminas Biogênicas/metabolismo , Ácido Glutâmico/metabolismo , Neuropeptídeos/metabolismo , Animais , Gânglios da Base/efeitos dos fármacos , Ratos
16.
Biol Psychiatry ; 42(4): 247-59, 1997 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-9270901

RESUMO

Behavioral, biochemical, and electrophysiological studies suggest that amperozide affects mesolimbic and mesocortical dopamine neurotransmission. The receptor binding profile of amperozide is discussed and related to behavioral and clinical, i.e., antipsychotic, effects of the drug. As previously reported, amperozide displayed high affinity for serotonin 5-HT2A receptors (Ki = 16 nmol/L), and moderate affinity for striatal dopamine D2 (Ki = 540 nmol/L) and cortical alpha 1-adrenergic receptors (Ki = 172 nmol/L). In the present study amperozide displayed low affinity for several serotonin receptor subtypes as well as for the dopamine D4 receptor transfected in COS7 cells (Ki D4.2 = 769 nmol/L and Ki D4.4 = 384 nmol/L). Amperozide was very weak or did not interact with several other receptor species including adrenergic, histaminergic, muscarinic, benzodiazepine, gamma-aminobutyric acid, amino acid, opiate, and Ca channels; however, amperozide was found to compete for [3H]paroxetine binding for the serotonin transporter in the nanomolar range (Ki = 49 nmol/L). In vitro and in vivo binding potency of amperozide correlates best with behavioral effects, indicating 5-HT2A antagonism, although serotonin uptake inhibition may contribute to the effects of amperozide on dopamine neurotransmission. The metabolite of amperozide, FG5620, displayed 5-10 times lower pharmacologic activity than amperozide. These properties of amperozide may suggest that the antipsychotic effects of amperozide are mediated by 5-HT2A receptors, although 5-HT uptake inhibition and alpha 1-adrenergic receptor-mediated effects may be considered, particularly at higher doses.


Assuntos
Antipsicóticos/farmacologia , Sistema Nervoso Central/metabolismo , Piperazinas/farmacologia , Receptores de Droga/efeitos dos fármacos , Receptores de Neurotransmissores/metabolismo , Animais , Antipsicóticos/metabolismo , Antipsicóticos/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Ligação Competitiva/efeitos dos fármacos , Química Encefálica/efeitos dos fármacos , Linhagem Celular , Sistema Nervoso Central/efeitos dos fármacos , Eletrofisiologia , Técnicas In Vitro , Canais Iônicos/efeitos dos fármacos , Canais Iônicos/metabolismo , Piperazinas/metabolismo , Piperazinas/uso terapêutico , Ensaio Radioligante , Ratos , Receptores de Droga/metabolismo , Receptores de Neurotransmissores/efeitos dos fármacos
17.
Transplantation ; 42(4): 364-7, 1986 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-3020747

RESUMO

After successful transplantation, the major histocompatibility complex (MHC) antigens of kidney parenchymal cells are lost and no longer detectable in the graft, presumably due to administration of glucocorticosteroids. During rejection, the MHC antigens reappear in the graft parenchymal cells. The upregulation is possibly due to gamma-interferon released in situ by the allograft activated T (blast) cells. In this communication we demonstrate that cytomegalovirus (CMV) infection is invariably associated with an upregulation of the antigen display in the graft. In 12 of 14 (86%) cases with proved CMV disease, the display of class II antigens was associated with a cytological and/or clinical episode of rejection. In 223 transplant recipients without proved CMV disease transplanted during the same period, the frequency of late rejections was 17% (P less than 0.001). The results suggest that the display of class II antigens on the graft, mediated presumably by gamma-interferon as a consequence of CMV infection, is the reason for graft rejection in context of CMV disease.


Assuntos
Infecções por Citomegalovirus/imunologia , Antígenos de Histocompatibilidade Classe II/análise , Transplante de Rim , Rejeição de Enxerto , Humanos , Interferon gama/fisiologia , Rim/imunologia , Nefrite/imunologia , Fatores de Tempo , Transplante Homólogo
18.
Transplantation ; 46(1): 47-53, 1988 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-3293285

RESUMO

Serial fine-needle aspiration biopsies (FNAB) were used for clinical monitoring of human liver allografts. Nine liver allograft recipients were monitored with FNAB at 1-3 day intervals. No complications were recorded. All patients underwent at least 1 inflammatory episode of acute rejection; altogether 11 episodes, all reversible, were recorded. The inflammatory infiltrate consisted mainly of lymphoid cells, including lymphoid blasts, with minor involvement of monocytes, monoblasts, and macrophages. Further analysis of lymphoid cell subpopulations by immunoperoxidase techniques demonstrated an increase of T cells during rejection, both the CD4 (T4) and CD8 (T8) subsets were increased. A slight increase of B cells in the graft was also seen. The CD4/CD8 (T4/T8) ratio was first low, peaked at the onset, and decreased toward the end of the episode. No clear correlations to the intragraft cellular events were recorded in corresponding blood specimens. However, an episode of eosinophilia was seen in the blood at the beginning of rejection, correlating with fever in the recipient. Degenerative changes in the parenchymal cells and bile droplets in the hepatocytes, indicating cholestasis and hepatocyte damage, were seen during all episodes of rejection, and these changes persisted even 10 days after the inflammation had subsided. The FNAB-findings correlated well with biochemical laboratory parameters, but the diagnosis of rejection could be established by the FNAB already 1-5 days earlier than elevated serum values indicated liver dysfunction.


Assuntos
Hepatopatias/diagnóstico , Transplante de Fígado , Fosfatase Alcalina/sangue , Anticorpos Monoclonais , Antígenos de Diferenciação de Linfócitos T/análise , Bilirrubina/sangue , Biópsia por Agulha/métodos , Eosinofilia/complicações , Seguimentos , Rejeição de Enxerto , Humanos , Inflamação , Linfócitos/classificação
19.
Transplantation ; 39(3): 279-81, 1985 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-2983461

RESUMO

In a double-blind, controlled study 35 herpes simplex virus (HSV) antibody-positive patients were randomized to receive oral acyclovir 200 mg X 4 daily or placebo for 28 days following renal transplantation. The incidence of herpes virus infection was compared in both groups by weekly virus demonstration/isolation testing from throat swabs and urine, and by serum antibody demonstration. None of the 18 patients allocated to acyclovir showed any signs of HSV or varicella zoster virus (VZV) infection during the trial period, whereas 9 of 17 receiving placebo had signs of HSV (P less than 0.001) and 2 of VZV (P less than 0.05) infection. Because of systemic as well as local symptoms of infection in five of the placebo patients, the trial was interrupted and treatment with oral acyclovir instituted. All of them responded well with rapid disappearance of all symptoms. Cytomegalovirus (CMV) was isolated from the urine of two patients in both groups during the trial period; a significant antibody rise was seen later in three of them. There was no evidence of drug-related toxicity during the study.


Assuntos
Aciclovir/uso terapêutico , Infecções por Herpesviridae/prevenção & controle , Transplante de Rim , Administração Oral , Adulto , Anticorpos Antivirais/análise , Testes de Fixação de Complemento , Feminino , Herpes Labial/imunologia , Herpes Zoster/imunologia , Infecções por Herpesviridae/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória
20.
Neuroscience ; 65(2): 485-92, 1995 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7777163

RESUMO

Rats, receiving an intrathecal pretreatment of oligodeoxynucleotide complementary to c-fos mRNA (antisense), showed no increases in Fos protein or preprodynorphin messenger RNA in the outer laminae of the lumbar spinal cord when challenged 4 h later with a 50 microliters intraplantar injection of 5% formalin. Animals pretreated with saline or sense oligodeoxynucleotide showed marked increases in Fos protein (2 h after formalin challenge) and preprodynorphin mRNA (20 h after formalin challenge) in the lumbar region of the cord ipsilateral to the side of the injection. The behavioural consequences of antisense pretreatment were an increase in the formalin-induced licking/biting responses during the tonic, but not the acute phase. These observations could be interpreted as representing a sequence of events beginning with the formalin-induced increase in the transcription factor Fos, which in turn increases the synthesis of preprodynorphin messenger RNA resulting in the production of the dynorphin opioid peptides which then exert a modulatory antinociceptive action.


Assuntos
Dinorfinas/biossíntese , Oligonucleotídeos Antissenso/farmacologia , Medição da Dor/efeitos dos fármacos , Precursores de Proteínas/biossíntese , Proteínas Proto-Oncogênicas c-fos , Animais , Sequência de Bases , Northern Blotting , Colecistocinina/biossíntese , Formaldeído , Imuno-Histoquímica , Hibridização In Situ , Masculino , Dados de Sequência Molecular , RNA Mensageiro/biossíntese , Ratos , Ratos Wistar
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