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1.
Acta Paediatr ; 89(3): 310-9, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10772279

RESUMO

The aims of this study, which was part of a survey on adolescent sexual behaviour, were to investigate adolescents' experience of child sexual abuse and to present possible abuse-related problems. Representative samples of 2% of Sweden's 17-y-old male and female students and school non-attenders were selected in a two-step procedure. In all, 1943 students and 210 school non-attenders answered a self-administered anonymous questionnaire, distributed by school nurses. Six out of 170 questions dealt with personal experiences of child sexual abuse, i.e. age at onset, frequency of abuse and relationship to the offender. Peer abuse was excluded by the definitions used. The overall response rate was 92.2% for students and 44.2% for school dropouts. Among male and female students, 3.1% and 11.2%, respectively, acknowledged sexual abuse, 2.3% and 7.1%, respectively, when exhibitionism was excluded. Mean age at onset was 9.1 y (SD 4.3) for boys and 9.0 y (SD 3.9) for girls; 1.2% of the boys and 3.1% of the girls reported abusive oral, vaginal and/or anal intercourse. Suicide attempts or other acts of self-harm were reported by 33.3% of the male students reporting abuse and by 5.1% (p < 0.001) of those who had not been abused, and by 30.4% of the abused student girls compared to 9.1% of the non-abused (p < 0.001). Sleep and eating disorders, use of alcohol at an early age and/or experimentation with illicit drugs and consensual coitarche before age 15 y was reported significantly more often by abused than non-abused girls (p < 0.001, differences not found among the student boys). Of school non-attenders, 4% of the boys and 28% of the girls reported sexual abuse. Of the abused girls, 49% reported abusive vaginal intercourse and 64% reported self-destructive behaviour or suicide attempts. No abused boys and few abused girls had confided in a teacher, health professional or social worker. Results from the student sample should be interpreted as markers of "minimum prevalence", as female school non-attenders report significantly higher prevalence of sexual abuse. Potential high-risk groups are better included in prevalence investigations of child sexual abuse. The fact that so few adolescents confided in "professionals" about the abuse, despite having severe symptoms and signs of distress, underlines the need to address sexual abuse when recording the social, medical and psychiatric histories of adolescents.


Assuntos
Abuso Sexual na Infância/estatística & dados numéricos , Adolescente , Abuso Sexual na Infância/psicologia , Coleta de Dados , Feminino , Humanos , Masculino , Projetos Piloto , Prevalência , Comportamento Sexual/psicologia , Inquéritos e Questionários , Suécia/epidemiologia
2.
Forensic Sci Int ; 104(1): 1-15, 1999 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-10533272

RESUMO

OBJECTIVE: The aim of the study was to summarize the history of assault and record the results of medicolegal examination in adolescent girls under investigation for alleged sexual abuse, and to monitor the outcome of the legal process. The investigation period was 1990-94. METHOD: A consecutive series of 94 0-para girls, aged 9-22, median age 15.0 years, were examined in the head-to-toe manner including anogenital examination. Girls were referred from investigating police and social authorities. Only non-acute examinations were performed. Findings considered consistent with abusive vaginal penetration were hymenal distortion including deep clefts, hymenal and vestibular scarring, and introital diameter permitting vaginal inspection with a 17 mm speculum in the absence of consensual intercourse. Perianal scarring was recorded. STD sampling was made on indication. Findings were documented on body sketches. Medicolegal conclusions were grouped into three categories according to history and physical findings. Information on the outcome of legal procedures was collected from referring authorities. RESULTS: For 82% (77/94) of the girls, referring agencies provided examining physicians with a detailed and consistent history of abuse, presented results comprise these 77 girls. Intrafamiliar abuse was alleged by 81% (62/77), onset prior to menarche by 53% (41/77), and repeated abuse by 74% (57/77) of the girls. Abusive genital penetration was reported by 77% (59/77) and anal penetration by 19% (14/77). Sequelae after admitted self-inflicted injury were found in 15% (12/77). Deep hymenal clefts and/or vestibular scars were found in 59% (35/59) of the girls reporting penetrative abuse, compared with 6% (1/16) when non-penetrative abuse was alleged, P < 0.001. Girls with experience of voluntary intercourse could all be examined with a 25 mm speculum. Of the 17 girls without experience of consensual intercourse but alleging abusive penetration, 47% (17/36) could easily be examined with a 17 mm speculum, compared to none of 13 reporting non-penetrative abuse, P < 0.001. Non-specific anal abnormalities occurred in 10 (13%) girls; more often when anal abuse was reported, P < 0.001. No specific STDs were found. The medicolegal conclusion supported a history of abusive genital penetration in 41 (69%) cases; findings were non-specific in 11 cases and a normal anogenital status was found in 25 cases. The alleged abuse of 34 of the 77 (44%) girls was tried in court. One suspect was acquitted, 32 men were convicted of the abuse of 33 girls. Eleven perpetrators admitted abuse, and their histories were in concordance with the abuse alleged by the victims, as well as with the physical findings. CONCLUSION: A medicolegal diagnosis of alleged non-acute cases of sexual abuse relies on a detailed history. Adolescent girls alleging abuse may exhibit signs of admittedly self-inflicted extragenital injury. Our findings confirm that non-penetrative sexual acts leave no lasting genital signs, but that repeated abusive genital penetration significantly more often than non-penetrative abuse leaves deep posterior hymenal clefts and/or vestibular scarring, and a hymenal opening allowing examination with 17-25 mm specula also in girls without experience of voluntary intercourse. In cases with a confessing perpetrator, no discordance was found between the history of the victim, medicolegal conclusion and the history of the perpetrator.


Assuntos
Delitos Sexuais/classificação , Delitos Sexuais/legislação & jurisprudência , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Anamnese/estatística & dados numéricos , Exame Físico/estatística & dados numéricos , Delitos Sexuais/estatística & dados numéricos , Suécia
3.
J Trauma Stress ; 11(1): 103-12, 1998 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9479679

RESUMO

The study comprises 149 refugees from various countries, reporting exposure to severe traumata, who were referred for psychiatric diagnosis and assessment of suicide risk. The stressors reported comprised both personal experience of and/or forced witnessing of combat atrocities (including explosions or missile impacts in urban areas), imprisonment (including isolation), torture and inflicted pain, sexual violence, witnessing others' suicide, and of summary and/or mock executions. Posttraumatic stress disorder (PTSD) was diagnosed in 79% of all cases, other psychiatric illness in 16% and no mental pathology in 5%. The prevalence of suicidal behavior was significantly greater among refugees with principal PTSD diagnoses than among the remainder. PTSD patients with depression comorbidity reported higher frequency of suicidal thoughts; PTSD nondepressive patients manifested increased frequency of suicide attempts.


Assuntos
Transtornos Mentais/epidemiologia , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Tentativa de Suicídio/estatística & dados numéricos , Tortura/psicologia , África/etnologia , Ásia/etnologia , Distribuição de Qui-Quadrado , Comorbidade , Europa Oriental/etnologia , Feminino , Humanos , América Latina/etnologia , Masculino , Oriente Médio/etnologia , Prevalência , Refugiados , Transtornos de Estresse Pós-Traumáticos/psicologia , Tentativa de Suicídio/psicologia , Suécia/epidemiologia , Tortura/estatística & dados numéricos
4.
J Trauma Stress ; 11(1): 113-24, 1998 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9479680

RESUMO

The study reports on 65 refugees with diagnoses of posttraumatic stress disorder (PTSD) and manifest suicidal behavior (40% had suicide attempts; 29% detailed suicide plan; 31% recurrent suicidal thoughts). Our hypothesis was that the predominant kind of stressful experience in PTSD patients might be reflected in their choice of method when pondering or attempting suicide. Relationships were found to exist between the main stressors and the respective subjects' preference for suicide method. Particularly among PTSD patients with a history of torture, an association was found between the torture methods that the victim had been exposed to, and the suicide method used in ideation or attempts. Blunt force applied to the head and body was associated with jumping from a height or in front of trains, water torture with drowning, or sharp force torture with methods involving self-inflicted stabbing or cutting. Relationships between main stressors and content of suicidal ideation are discussed.


Assuntos
Transtornos de Estresse Pós-Traumáticos/psicologia , Tentativa de Suicídio/psicologia , Tortura/classificação , África/etnologia , Europa Oriental/etnologia , Feminino , Humanos , América Latina/etnologia , Masculino , Oriente Médio/etnologia , Refugiados , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Tentativa de Suicídio/estatística & dados numéricos , Suécia/epidemiologia , Tortura/psicologia , Tortura/estatística & dados numéricos , Ferimentos não Penetrantes/psicologia , Ferimentos Penetrantes/psicologia , Iugoslávia/etnologia
5.
Forensic Sci Int ; 78(2): 157-63, 1996 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-8621122

RESUMO

In Sweden, ca. 25% of unnatural deaths ascribed to self-inflicted injury are finally recorded as 'undetermined suicide' (abbreviated UMSA), i.e. the forensic pathologist has not been able to establish whether the fatality was an accident or a suicide. In the present study, a series of UMSA cases was investigated with the aims to study the impact of immigrant status, and alcohol abuse on the occurrence of this forensic diagnosis on the mode of death. The alcohol issue was addressed by focusing on blood alcohol concentrations at autopsy (BAC) and post mortem signs of alcohol-related organ pathology. The results can be summarised as follows: Positive BAC occurred at an equal rate in the UMSA group and in definite suicides, i.e. about 45%. Among non-Swedish UMSA victims positive BAC was more common (50%) than among the Swedish (41%), whereas no difference was found in the definite suicide group. The level of BAC at autopsy was significantly higher in Finnish immigrants than in other ethnic groups. Organic signs of chronic alcohol abuse were found in 13 of 40 cases testing positive for BAC; thus, presence of alcohol at autopsy may reflect incidental intake rather than habitual overconsumption.


Assuntos
Etanol/sangue , Suicídio/etnologia , Causas de Morte , Cultura , Emigração e Imigração , Finlândia/etnologia , Medicina Legal , Humanos , Hepatopatias Alcoólicas/diagnóstico , Hepatopatias Alcoólicas/etnologia , Hepatopatias Alcoólicas/patologia , Suécia/epidemiologia
6.
Acta Psychiatr Scand ; 91(2): 130-5, 1995 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-7778471

RESUMO

A total of 707 cases of violent death (suicide, undetermined mode or accident) occurring in 1990 were investigated at the Department of Forensic Medicine in Stockholm. The catchment area of the Department includes about 1.9 million people. Fourteen percent of the population in the area are immigrants. The largest single immigrant group was the 91,015 Finnish-born inhabitants, who represented 33% of the overall immigrant population. Thirty percent of all undetermined deaths and 20% of the suicides were among people born outside Sweden. A significant overrepresentation of the largest immigrant group (Finnish-born) was found in both the definite and undetermined suicide categories. There was also an overall overrepresentation of immigrants among the undetermined cases and a trend towards overrepresentation among definite suicides. Also, there was a significant overall overrepresentation of immigrants in the total cases of undetermined and definite suicide. Some psychosocial factors found predominant among the immigrant sample were social isolation, low social class and poor social network. The findings in this study indicates that immigrant status should be considered as a risk factor for suicide in Sweden. Previous reports on the high suicide rates among immigrants in Australia, Canada, Great Britain and the United States suggest that the overrepresentation of immigrants found in our study could represent a worldwide epidemiological trend related to voluntary and forced migration. Possible hypotheses that could explain this phenomenon are discussed.


Assuntos
Emigração e Imigração , Suicídio/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Idoso , Emprego , Feminino , Finlândia , Humanos , Masculino , Estado Civil , Pessoa de Meia-Idade , Fatores Sexuais , Isolamento Social , Suécia/epidemiologia , Suécia/etnologia
7.
J Forensic Sci ; 38(6): 1409-21, 1993 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8263483

RESUMO

During the years 1980-1992 the Swedish legislation regarding possession and use of firearms has remained fairly unchanged. Simultaneously the reported incidence of both stolen firearms and confiscation of illegally possessed handguns has increased significantly. In order to determine the impact of this trend on gunshot mortality, all victims of firearm fatalities subjected to medicolegal autopsy in the Stockholm area 1980-81 and 1990-91 were studied. The overall two-year rate increased from 50 to 65, homicides and suicides contributing seven new cases each; accidents and "not determined" comprising only 0 to 2 cases in each period. Suicides were four times as common as homicides in the former period; ca. three times as common in the latter. Thus, a 70% increase in homicidal shooting has occurred (from 10 to 17), and the fatal use of illegal firearms increased from 50% to 93%. As expected, there was a definite male dominance (96%) among perpetrators as well as among victims (85%). Concerning suicides, the rate in the latter period was 18% above that in the former; illegal guns were used in 30% in 1990-91 as compared to 20% 1980-81. The pattern of wounding in suicides was similar to that reported in earlier studies; confirming that entrance wounds in the back, extremities and lower abdomen are indicative of homicide. Thus, common sense knowledge of firearm fatalities are confirmed: More widespread access to illegal weapons conveys a higher rate of gunshot fatalities. The perpetrator is likely to be male. Suicidal shots are usually aimed at the head (mouth, temple, forehead) or precordium. Most gunshot suicides are committed by means of legally possessed firearms.


Assuntos
Armas de Fogo/estatística & dados numéricos , Homicídio/estatística & dados numéricos , Suicídio/estatística & dados numéricos , Ferimentos por Arma de Fogo/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Etanol/sangue , Feminino , Armas de Fogo/legislação & jurisprudência , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Suécia/epidemiologia
8.
Toxicol Pathol ; 21(5): 443-8, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8115821

RESUMO

The nephrotoxicity of hexachlorobutadiene has been investigated in germ-free rats and compared to conventional rats that have a normal intestinal microflora. Presynthesized mercapturate intermediates of hexachlorobutadiene, the glutathione and the cysteine S-conjugate, were also administered. Germ-free rats appeared to be slightly more susceptible to hexachlorobutadiene by judging the extent of morphological changes compared to conventional ones. A similar response was also observed after treatment with the glutathione and cysteine S-conjugates. However, no significant difference between germ-free and conventional animals was monitored in the extent of elevation of blood urea nitrogen and plasma creatinine after treatment with hexachlorobutadiene or the glutathione and the cysteine S-conjugates. The urinary excretion of marker enzymes was monitored and showed that gamma-glutamyl transferase was significantly more increased in the germ-free rats when treated with the cysteine S-conjugate. In addition, no difference in the rate of glutathione conjugation of hexachlorobutadiene was measured between the two groups. Although a tendency toward a protective effect by the presence of an intestinal microflora was observed, the role of the intestinal microflora in detoxifying hexachlorobutadiene seems to be of limited importance in rats.


Assuntos
Butadienos/toxicidade , Intestinos/microbiologia , Nefropatias/induzido quimicamente , Animais , Butadienos/metabolismo , Vida Livre de Germes , Glutationa Transferase/fisiologia , Masculino , Ratos
9.
Nord Med ; 107(5): 141-4, 1992.
Artigo em Sueco | MEDLINE | ID: mdl-1603663

RESUMO

Most battered women consult for their injuries at the community health centre or the emergency room--often without disclosing the fact that they are the victims of battery. Beyond venturing to inquire, lending a sympathetic ear and being supportive, with a view to any future criminal proceedings it is particularly important that the attending physician meticulously documents all injuries manifested by a battered woman--even if at that juncture she does not intend to bring charges. If necessary the forensic pathologist can assist the clinician in drawing up a report of the injuries and in assessing their origin.


Assuntos
Documentação , Maus-Tratos Conjugais/diagnóstico , Adolescente , Adulto , Centros Comunitários de Saúde , Serviço Hospitalar de Emergência , Feminino , Medicina Legal , Humanos , Pessoa de Meia-Idade , Maus-Tratos Conjugais/patologia
11.
In Vitro Cell Dev Biol ; 27A(7): 562-8, 1991 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-1716253

RESUMO

Human buccal epithelial cells have been reared from explants maintained in supplemented MCDB 153 medium. Primary epithelial outgrowths show typical structural features and uniformly express keratins; subunit analyses demonstrate expression of keratins 5, 6, 14, 16/17, and 19. The cells exhibit up to 6% colony forming efficiency and divide at about 0.8 population doublings per day on fibronectin/collagen-coated dishes at clonal density. Studies of markers of proliferation and differentiation in buccal epithelial cells indicate that epidermal growth factor, cholera toxin, retinoic acid, and pituitary extract each exhibit a distinctive ability to enhance growth and variably affect cell migration and cell surface area. Transforming growth factor beta-1 inhibits growth and increases surface area without affecting migration, involucrin expression, and cross-linked envelope formation. Moreover, exposure of cells to fetal bovine serum, the tumor promoting agent 12-O-tetradecanoylphorbol-13-acetate or an elevated Ca2+ concentration (from 0.1 to 1 mM) inhibits growth and induces squamous differentiation as indicated by inhibition of migration, increases in surface area, involucrin expression, or formation of cross-linked envelopes. The results show that epithelial cells can be reproducibly derived from explant cultures of human buccal mucosa specimens and the cells transferred under serum-free conditions. Buccal epithelial cells in culture undergo a pattern of growth and differentiation that mimics parakeratinization in vivo and variably respond to several agents shown to modulate growth of cells that originate from other types of epithelia.


Assuntos
Mucosa Bucal/citologia , Animais , Sangue , Cálcio/farmacologia , Bovinos , Divisão Celular , Toxina da Cólera/farmacologia , Meios de Cultura , Fator de Crescimento Epidérmico/farmacologia , Células Epiteliais , Epitélio/metabolismo , Humanos , Técnicas In Vitro , Queratinas/metabolismo , Microscopia Eletrônica de Varredura , Mucosa Bucal/metabolismo , Hormônios Hipofisários/farmacologia , Acetato de Tetradecanoilforbol/farmacologia , Fator de Crescimento Transformador beta/farmacologia , Tretinoína/farmacologia
12.
Acta Paediatr Scand ; 78(6): 935-43, 1989 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-2603722

RESUMO

Twenty-nine children were subjected to physical examination as part of a population-based study comprising 41 children, aged 0-17 years, all assumed to be victims of sexual abuse. The hymenal opening was measured with transparent test tubes of known diameters using a new, simple and reproducible method. The examination was in no case performed under anaesthesia. A dilated hymenal opening and/or other physical evidence of trauma or disease were found in 19/29 children. Examination results evaluated in the light of anamnestic information indicated that sexual abuse had occurred in 10 cases but in only 3 of these cases the suspect was convicted. Additional studies are required to shed light on age-related normal variations in genital anatomy.


Assuntos
Abuso Sexual na Infância/diagnóstico , Adolescente , Criança , Abuso Sexual na Infância/legislação & jurisprudência , Abuso Sexual na Infância/psicologia , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Exame Físico , Suécia
13.
J Forensic Sci ; 33(2): 448-61, 1988 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-3373161

RESUMO

A total of 89 cases of sharp force suicide that had been committed in the Stockholm area in Sweden from 1972 through 1984 were investigated. The series showed a male preponderance, sex ratio 3.3, and among males a shift towards the age group 40 to 49 years of age. An impact of cultural/ethnic factors was indicated by the overrepresentation of Finnish and Hungarian immigrants. A psychiatric diagnosis had been ascribed in 22 cases, and addiction to drugs or alcohol in 23. Previous attempts at self-destruction were recorded in 11 cases, only 1 of which was by sharp force. Classical indicators of suicidal intent, for example, suicide notes and the presence of hesitation injuries, were found in 28 and 80%, respectively. A preference for certain anatomical locations (throat, precordium, epigastrium, wrists) was confirmed as was the tendency to expose the skin before inflicting suicidal wounds. As compared to homicidal precordial stabs whose entrance wounds usually run vertically, horizontal or upwards/left-slanting stabs are strongly suggestive of suicide. Although cases were encountered where several "rules of thumb" concerning homicidal versus suicidal patterns were violated, our series contained no case of injuries to the backside of the trunk and no case of more than one wound piercing the left ventricle of the heart. Multiple chest wounds transecting costal or sternal bone were however not uncommon, and, along with the use of bizarre tools and objects like wood chisels or pieces of glass, illustrated the determination of suicidal intent. Toxicological analysis was positive for drugs in 22 and for alcohol in 27 cases. Blood alcohol levels were roughly similar to those found in victims of homicidal sharp force, whereas drug levels tended to be lower or higher in suicides.


Assuntos
Suicídio/epidemiologia , Ferimentos Perfurantes/mortalidade , Adulto , Alcoolismo/epidemiologia , Feminino , Finlândia/etnologia , Humanos , Hungria/etnologia , Masculino , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Suicídio/etnologia , Suicídio/psicologia , Suécia , Ferimentos Perfurantes/etnologia , Ferimentos Perfurantes/psicologia
14.
Chem Biol Interact ; 68(1-2): 1-11, 1988.
Artigo em Inglês | MEDLINE | ID: mdl-3203401

RESUMO

Hepatic GSH conjugation is the initial step in the mammalian biotransformation of hexachloro-1,3-butadiene (HCBD) and analogous haloalkenes. The present paper reports an in vitro investigation of the glutathione-dependent conversion of HCBD to water-soluble products, i.e. the enzyme-catalyzed conjugation of HCBD with GSH. The method employed avoids artifacts due to the volatility, low solubility and hydrophobic nature of the chloro-carbon substrate. In order to assess the relative importance of membrane-bound and cytosolic glutathione S-transferase in the conjugation process, microsomal and cytosolic fractions from adult rat liver were tested separately for their ability to promote water solubilisation of the substrate. In addition, microsomal purified and liposomally reconstituted glutathione S-transferase, were tested. The reaction exhibited Michaelis-Menten kinetics, and conjugation rates were linear for at least 20 min. The hepatic microsomal fraction metabolized HCBD 116 times faster than the cytosolic fraction when substrate saturated. Both mono- and bis-substituted conjugates were formed by microsomal as well as by the cytosolic fraction. Treatment of animals with inducers and the use of specific inhibitors indicated absence of cytochrome P-450 involvement in the formation of water soluble HCBD metabolites and supported the view that microsomal glutathione S-transferase is more important in catalyzing GSH conjugation of this haloalkene than the cytosolic forms of transferases.


Assuntos
Butadienos/farmacocinética , Citosol/metabolismo , Glutationa , Microssomos Hepáticos/metabolismo , Animais , Inibidores das Enzimas do Citocromo P-450 , Citosol/enzimologia , Indução Enzimática , Glutationa Transferase/metabolismo , Substâncias Macromoleculares , Masculino , Microssomos Hepáticos/enzimologia , Fenobarbital , Ratos , Ratos Endogâmicos , Solubilidade
15.
Arch Biochem Biophys ; 258(2): 365-72, 1987 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-3674880

RESUMO

The subcellular mechanism of alkenyl halide S-conjugate-induced nephrotoxicity was studied in mitochondria isolated from rat kidney cortex in vitro using the cysteine conjugate of hexachloro-1,3-butadiene, i.e., S-pentachlorobutadienyl-L-cysteine (PCBC) as a model substrate. Respiring mitochondria exposed to various concentrations of PCBC exhibited a dose-dependent loss of ability to retain calcium. This phenomenon was associated with a sudden collapse of the mitochondrial membrane potential. PCBC caused a slow nonenzymatic depletion of mitochondrial glutathione. This was not due to oxidation or formation of mixed disulfides, and was efficiently counteracted by preincubation with aminooxyacetic acid, an inhibitor of cysteine-conjugate beta-lyase activity. PCBC inhibited state 3 respiration in the presence of succinate as substrate, which indicates that the activity of succinate dehydrogenase was affected. Thus, the present data confirm that impairment of mitochondrial function is a feature of nephrotoxicity mediated by alkenyl halide S-conjugates. We suggest a pathway involving interaction of beta-lyase-dependent reactive metabolite with the mitochondrial inner membrane, loss of membrane potential, disturbance of Ca2+ homeostasis, and subsequent respiratory insufficiency as a mechanism for renal tubular cytotoxicity.


Assuntos
Butadienos/toxicidade , Cisteína/análogos & derivados , Córtex Renal/metabolismo , Mitocôndrias/metabolismo , Ácido Amino-Oxiacético/farmacologia , Animais , Cálcio/metabolismo , Cisteína/metabolismo , Cisteína/toxicidade , Glutationa/metabolismo , Membranas Intracelulares/efeitos dos fármacos , Membranas Intracelulares/fisiologia , Córtex Renal/efeitos dos fármacos , Córtex Renal/patologia , Cinética , Masculino , Potenciais da Membrana/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/fisiologia , Consumo de Oxigênio/efeitos dos fármacos , Ratos , Ratos Endogâmicos
16.
Arch Biochem Biophys ; 251(2): 504-13, 1986 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-3800381

RESUMO

Isolated renal epithelial cells were used to study the mechanism of toxicity of pentachlorobutadienyl-glutathione (PCBG), a nephrotoxic glutathione conjugate of hexachlorobutadiene. The cytotoxicity of PCBG displayed a very steep dose-response relationship; at 10 microM PCBG no toxicity was observed whereas 25, 50, and 100 microM PCBG all resulted in a similar degree of toxicity. In all cases, loss of cell viability was observed only after a 30-min lag period and reached a plateau of 50 to 60% nonviable cells between 90 and 100 min. Toxic doses of PCBG also resulted in the depletion of cellular thiols. Blocking PCBG metabolism by inhibition of gamma-glutamyl transpeptidase [1-gamma-L-glutamyl-2-(2-carboxyphenyl)hydrazine (anthglutin), 2 mM] or renal cysteine conjugate beta-lyase (aminooxyacetic acid, 0.5 mM) resulted in complete protection against PCBG-induced cell damage. Exposure of isolated renal epithelial cells to 100 microM PCBG resulted in the rapid formation of plasma membrane blebs which appeared to be associated with a loss of Ca2+ from the mitochondrial compartment and an elevation of cytosolic Ca2+ concentration as measured by Quin-2. PCBG treatment also resulted in the inhibition of cell respiration and a marked depletion of cellular ATP content, indicating additional mitochondrial effects of the toxin. Our results support a role for renal cysteine conjugate beta-lyase in the metabolic activation of PCBG and suggest that PCBG-induced renal cell injury may be the result of selective effects on mitochondrial function.


Assuntos
Butadienos/toxicidade , Glutationa/análogos & derivados , Rim/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Aminoquinolinas , Animais , Butadienos/antagonistas & inibidores , Cálcio/metabolismo , Membrana Celular/efeitos dos fármacos , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Corantes Fluorescentes , Glutationa/antagonistas & inibidores , Glutationa/toxicidade , Técnicas In Vitro , Rim/metabolismo , L-Lactato Desidrogenase/metabolismo , Masculino , Mitocôndrias/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Ratos , Ratos Endogâmicos
17.
J Forensic Sci ; 31(2): 529-42, 1986 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-3711828

RESUMO

A ten-year series of 142 homicidal fatalities caused by sharp force injury was studied with the aim to systematize information inherent in the characteristics of the victim and the pattern of injuries. The population of victims consisted of 112 males (79%) and 30 females (21%); among perpetrators, 125 (88%) were males. Among victims as well as among perpetrators, persons of non-Swedish origin were overrepresented in relation to their share of the nonselected population. In 82 cases (58%), one or two wounds had been inflicted; in 23 cases (16%), ten or more wounds. In the latter group, eleven victims but no perpetrators were female. In the majority of cases victim and perpetrator were known to each other, and in instances of multiple wounding, a close relationship between the two was clearly more common than in the group of one- to two-wound fatalities. Tests for blood alcohol were positive in 86 of 116 victims (74%), the majority being in elimination phase. Furthermore, 96 of 120 perpetrators (80%) had positive tests or were known to be drunk at the time of the killing. In multiple wound fatalities, alcohol inebriation was less common both among victims and perpetrators. In these cases, the two persons involved were usually closely related or intimately known to each other, and in the absence of psychiatric disorder in the assailant, the motive was of a passionate type.


Assuntos
Medicina Legal/métodos , Homicídio , Ferimentos Perfurantes/patologia , Acidentes , Consumo de Bebidas Alcoólicas , Etanol/sangue , Etnicidade , Feminino , Humanos , Masculino , Pele/patologia , Suécia , Violência
18.
Chem Biol Interact ; 56(2-3): 251-67, 1985 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-4075451

RESUMO

The nephrotoxicity of hexachloro-1,3-butadiene (HCBD) appears to depend on the initial formation of a glutathione (GSH) conjugate in the liver. In the present study we have examined the hepatic metabolism of HCBD using isolated hepatocytes and following in vivo administration. Exposure of isolated hepatocytes to HCBD resulted in a dose-dependent depletion of GSH. HPLC analysis of the incubation medium demonstrated the formation of two products. When isolated hepatocytes containing [3H]GSH were exposed to [14C]HCBD, coincident elution of 3H and 14C corresponding to the previously recognized HPLC peaks was observed. Both products were sensitive to treatment with gamma-glutamyl transpeptidase (gamma-GT), providing additional support for their identification as GSH conjugates. The ratio of 3H to 14C in the two peaks indicated the formation of both a mono- and a bis-substituted GSH conjugate of HCBD. The identification of the mono- and bis-GSH conjugates was further confirmed by the preparation of synthetic standards which displayed retention times by HPLC identical to the biological products. The production of the total and individual GSH conjugates displayed both dose and time dependence. The production of the total as well as the ratio of mono- to bis-conjugate was found to depend on the availability of GSH. At low HCBD exposure levels the bis-substituted conjugate accounted for more than 20% of the total conjugate produced by isolated hepatocytes. This value decreased at higher HCBD concentrations. Analysis of bile collected from rats following intraportal administration of [14C]HCBD revealed the presence of both the mono- and bis-substituted GSH conjugates of HCBD as well as additional 14C-containing metabolites. The results of the present study clearly demonstrate the production of both a mono- and a bis-substituted GSH conjugate of HCBD. The potential importance of this finding in terms of the nephrotoxicity of HCBD is discussed.


Assuntos
Butadienos/metabolismo , Fungicidas Industriais/metabolismo , Glutationa/metabolismo , Fígado/metabolismo , Animais , Biotransformação , Butadienos/isolamento & purificação , Radioisótopos de Carbono , Técnicas In Vitro , Cinética , Masculino , Espectrometria de Massas , Ratos , Ratos Endogâmicos , Relação Estrutura-Atividade
19.
Chemioterapia ; 4(5): 343-8, 1985 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-4075431

RESUMO

Several xenobiotics undergo biotransformation reactions which yield reactive and potentially toxic compounds. Activation may occur via cytochrome P-450-mediated oxidation, prostaglandin synthetase-related hydroperoxidase-activity, or alcohol dehydrogenase/aldehyde dehydrogenase activity. The reactive metabolites thus formed may initiate lipid peroxidation or covalent binding to cell macromolecules, and secondarily lead to acute cytotoxicity or to tumorigenesis. Most cells possess mechanisms for protection against chemical toxicity, e.g. glutathione-related pathways and epoxide hydrolase activity. A possible strategy in handling toxic drug effects in the clinical situation may be chemotherapeutic manipulations aiming at a stimulation of protective mechanisms or at an inhibition of activating pathways.


Assuntos
Biotransformação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Acetaminofen/metabolismo , Animais , Fenômenos Químicos , Química , Sistema Enzimático do Citocromo P-450/metabolismo , Epóxido Hidrolases/metabolismo , Glutationa/metabolismo , Humanos , Técnicas In Vitro , Rim/efeitos dos fármacos , Rim/metabolismo , Peróxidos Lipídicos/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , NADH NADPH Oxirredutases/metabolismo , Oxigênio/metabolismo
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