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1.
Vet Ophthalmol ; 24(2): 209-215, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33608958

RESUMO

INTRODUCTION: Classically, sporotrichosis occurs as a chronic granulomatous lymphocutaneous infection. The extracutaneous form is uncommon and may affect the eye without cutaneous involvement. The most frequent form of ocular sporotrichosis reported in humans is a granulomatous conjunctivitis. There are no previous reports on primary ocular sporotrichosis in cats. PROCEDURES: Three mixed breed cats rescued from shelters were referred by the veterinarian for ophthalmic evaluation with a complaint of conjunctivitis nonresponsive to treatment with no evidence of skin disease or systemic disease. Complete ophthalmic examination, conjunctival cytology, and microbiological analysis were performed. RESULTS: Ophthalmic examinations revealed epiphora, purulent ocular discharge, conjunctival hyperemia, and a mass in the palpebral conjunctiva. Conjunctival cytology revealed segmented and degenerated neutrophils, conjunctival epithelial cells, and an abundant number of round and oval cells compatible with Sporothrix spp. Microbiological culture was performed and confirmed the presence of fungi from the Sporothrix schenckii complex. All animals were treated with oral itraconazole; two animals received topical itraconazole in association with oral treatment. Case 1 was refractory to treatment, and iodate potassium was combined with itraconazole therapy without resolution at the time of this publication. Cases 2 and 3 had complete resolution of conjunctival lesions with four months of oral and topical itraconazole therapy. CONCLUSION: Conjunctival sporotrichosis should be considered as a differential diagnosis of conjunctivitis in cats from endemic regions. Conjunctival cytology is an important tool that can aid early diagnosis.


Assuntos
Doenças do Gato/microbiologia , Doenças da Túnica Conjuntiva/veterinária , Sporothrix , Esporotricose/veterinária , Administração Oral , Animais , Antifúngicos/uso terapêutico , Brasil , Doenças do Gato/tratamento farmacológico , Gatos , Doenças da Túnica Conjuntiva/tratamento farmacológico , Doenças da Túnica Conjuntiva/microbiologia , Feminino , Itraconazol/uso terapêutico , Masculino , Esporotricose/tratamento farmacológico , Esporotricose/microbiologia
2.
Endocrine ; 71(1): 104-112, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32419081

RESUMO

PURPOSE: CTLA4, PTPN22, and CD40 are immune-regulatory genes strongly associated with GD, as well as PPARG, but their clinical significance in different populations is still uncertain. METHODS: We genotyped 282 Brazilian GD patients (234 women and 48 men, 39.80 ± 11.69 years old), including 144 patients with GO, and 308 healthy control individuals (246 women and 62 men, 36.86 ± 12.95 years old). RESULTS: A multivariate analysis demonstrated that the inheritance of the GG genotype rs3087243 of CTLA4 (OR = 2.593; 95% CI = 1.630-4.123; p < 0.0001) and the CC genotype of rs3789607 of PTPN22 (OR = 2.668; 95% CI = 1.399-5.086; p = 0.0029) consisted in factors independent of the susceptibility to GD. The inheritance of polymorphic genotypes of rs5742909 of CTLA4 was associated with older age at the time of diagnosis (42.90 ± 10.83 versus 38.84 ± 11.81 years old; p = 0.0105), with higher TRAb levels (148.17 ± 188.90 U/L versus 112.14 ± 208.54 U/L; p = 0.0229) and the need for higher therapeutic doses of radioiodine (64.23 ± 17.16 versus 50.22 ± 16.86; p = 0.0237). The inheritance of the CC genotype of rs1883832 CD40 gene was more frequent among women (69.65%) than men (52.00%; p = 0.0186). The polymorphic genotype of PPARG gene (rs1801282) was associated with TPOAb positivity (p = 0.0391), and the GG genotype of rs2476601 of PTPN22 gene was associated with positivity for both TgAb (p = 0.0360) and TPOAb (p < 0.0001). Both polymorphic genotypes rs2476601 and rs3789607 of the PTPN22 gene were more frequent among nonsmoking patients (p = 0.0102 and p = 0.0124, respectively). CONCLUSIONS: Our data confirm the important role of CTLA4 polymorphisms in GD susceptibility; demonstrate the role of PTPN22 polymorphisms in patients' clinical features; and suggest these genes may influence the severity of the disease.


Assuntos
Antígenos CD40/genética , Antígeno CTLA-4 , Doença de Graves , PPAR gama , Proteína Tirosina Fosfatase não Receptora Tipo 22 , Adulto , Idoso , Brasil , Antígeno CTLA-4/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Radioisótopos do Iodo , Masculino , Pessoa de Meia-Idade , PPAR gama/genética , Polimorfismo de Nucleotídeo Único , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética , Adulto Jovem
3.
Eur J Neurosci ; 31(5): 903-9, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20180839

RESUMO

Although the involvement of the medial prefrontal cortex projection to the nucleus accumbens in the reinstatement of cocaine seeking has been well studied, it is not known if this projection plays a similar role in the reinstatement of cue- and methamphetamine-induced drug seeking in animals extinguished from methamphetamine self-administration. Accordingly, following extinction from long-access methamphetamine self-administration, rats were bilaterally microinjected with either a combination of the GABA agonists baclofen/muscimol or vehicle (artificial cerebrospinal fluid) into the infralimbic or prelimbic subcompartments of the medial prefrontal cortex or into the shell or core subcompartments of the nucleus accumbens. Similar to cocaine seeking, inactivation of either the prelimbic cortex or accumbens core eliminated cue- and methamphetamine-induced reinstatement, and inactivation of neither the infralimbic cortex nor shell subcompartments inhibited methamphetamine-induced drug seeking. However, in contrast to previous reports with cocaine, cue-induced reinstatement of methamphetamine seeking was inhibited by inactivation of the infralimbic cortex. In conclusion, although a primary role in reinstated drug seeking by the prelimbic and the accumbens core is similar between cocaine and methamphetamine, the recruitment of the infralimbic cortex by conditioned cues differs between these two psychostimulant drugs.


Assuntos
Comportamento Aditivo/fisiopatologia , Estimulantes do Sistema Nervoso Central/farmacologia , Cocaína/farmacologia , Metanfetamina/farmacologia , Núcleo Accumbens/fisiologia , Córtex Pré-Frontal/fisiologia , Animais , Sinais (Psicologia) , Masculino , Núcleo Accumbens/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Ratos , Ratos Long-Evans , Autoadministração , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia
4.
J Pharmacol Exp Ther ; 331(2): 555-62, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19648469

RESUMO

Chronic abuse of methamphetamine leads to cognitive dysfunction and high rates of relapse, paralleled by significant changes of brain dopamine and serotonin neurotransmission. Previously, we found that rats with extended access to methamphetamine self-administration displayed enhanced methamphetamine-primed reinstatement of drug-seeking and cognitive deficits relative to limited access animals. The present study investigated whether extended access to methamphetamine self-administration produced abnormalities in dopamine and serotonin systems in rat forebrain. Rats self-administered methamphetamine (0.02-mg/i.v. infusion) during daily 1-h sessions for 7 to 10 days, followed by either short- (1-h) or long-access (6-h) self-administration for 12 to 14 days. Lever responding was extinguished for 2 weeks before either reinstatement testing or rapid decapitation and tissue dissection. Tissue levels of monoamine transporters and markers of methamphetamine-induced toxicity were analyzed in several forebrain areas. Long-access methamphetamine self-administration resulted in escalation of daily drug intake ( approximately 7 mg/kg/day) and enhanced drug-primed reinstatement compared with the short-access group. Furthermore, long-, but not short-access to self-administered methamphetamine resulted in persistent decreases in dopamine transporter (DAT) protein levels in the prefrontal cortex and dorsal striatum. In contrast, only minor alterations in the tissue levels of dopamine or its metabolites were found, and no changes in markers specific for dopamine terminals or glial cell activation were detected. Our findings suggest that persistent methamphetamine seeking is associated with region-selective changes in DAT levels without accompanying monoaminergic neurotoxicity. Greater understanding of the neuroadaptations underlying persistent methamphetamine seeking and cognitive deficits could yield targets suitable for future therapeutic interventions.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/metabolismo , Monoaminas Biogênicas/metabolismo , Estimulantes do Sistema Nervoso Central/farmacologia , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Metanfetamina/farmacologia , Neostriado/metabolismo , Córtex Pré-Frontal/metabolismo , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Animais , Química Encefálica/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/toxicidade , Cromatografia Líquida de Alta Pressão , Sinais (Psicologia) , Dopamina/metabolismo , Extinção Psicológica , Masculino , Metanfetamina/administração & dosagem , Metanfetamina/toxicidade , Neostriado/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Ratos , Ratos Long-Evans , Recidiva , Autoadministração , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo
5.
Neurotoxicology ; 73: 58-80, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30836127

RESUMO

Lead is a neurotoxin that produces long-term, perhaps irreversible, effects on health and well-being. This article summarizes clinical and preclinical studies that have employed a variety of research techniques to examine the neurotoxic effects of low levels of lead exposure. A historical perspective is presented, followed by an overview of studies that examined behavioral and cognitive outcomes. In addition, a short summary of potential mechanisms of action is provided with a focus on calcium-dependent processes. The current level of concern, or reference level, set by the CDC is 5 µg/dL of lead in blood and a revision to 3.5 µg/dL has been suggested. However, levels of lead below 3 µg/dL have been shown to produce diminished cognitive function and maladaptive behavior in humans and animal models. Because much of the research has focused on higher concentrations of lead, work on low concentrations is needed to better understand the neurobehavioral effects and mechanisms of action of this neurotoxic metal.


Assuntos
Comportamento do Adolescente/efeitos dos fármacos , Desenvolvimento do Adolescente/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Comportamento Infantil/efeitos dos fármacos , Desenvolvimento Infantil/efeitos dos fármacos , Intoxicação do Sistema Nervoso por Chumbo em Adultos , Intoxicação do Sistema Nervoso por Chumbo na Infância , Adolescente , Adulto , Fatores Etários , Idoso , Animais , Encéfalo/crescimento & desenvolvimento , Criança , Pré-Escolar , Cognição/efeitos dos fármacos , Relação Dose-Resposta a Droga , História do Século XX , História do Século XXI , Humanos , Intoxicação do Sistema Nervoso por Chumbo em Adultos/história , Intoxicação do Sistema Nervoso por Chumbo em Adultos/fisiopatologia , Intoxicação do Sistema Nervoso por Chumbo em Adultos/psicologia , Intoxicação do Sistema Nervoso por Chumbo na Infância/história , Intoxicação do Sistema Nervoso por Chumbo na Infância/fisiopatologia , Intoxicação do Sistema Nervoso por Chumbo na Infância/psicologia , Camundongos , Pessoa de Meia-Idade , Ratos , Medição de Risco , Fatores de Risco , Testes de Toxicidade , Adulto Jovem
6.
Drug Alcohol Depend ; 95(1-2): 23-9, 2008 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-18242880

RESUMO

The rate of acquisition of drug self-administration and the return to drug seeking are important elements of the overall drug profile, and are essential factors in understanding risks associated with drug abuse. Experiment 1 examined the effects of perinatal (gestation/lactation) lead exposure on adult rates of acquisition of intravenous (i.v.) methamphetamine self-administration. Experiment 2 investigated the effects of perinatal lead exposure on drug-maintained responding in a reinstatement (relapse) paradigm. In Experiment 1, female rats were gavaged daily with 0 or 16 mg lead for 30 days prior to breeding with nonexposed males. Lead exposure continued through gestation and lactation and was discontinued at weaning (postnatal day [PND] 21). Male rats born to control or lead-exposed dams were tested daily as adults in an acquisition paradigm that incorporated both Pavlovian and operant components. An initial 3-h autoshaping period preceded a 3-h self-administration period. For 35 daily training sessions i.v. methamphetamine infusions [inf] (0.02 mg/kg) were paired with the extension and retraction of a lever (autoshaping), while inf occurred during self-administration only when a lever press was executed (FR-1). In Experiment 2 animals developmentally exposed to lead were trained on an FR-2 to self-administer methamphetamine (0.04 mg/kg/inf) and then placed on an extinction schedule prior to receiving intraperitoneal (i.p.) priming injections of saline, 0.50, 1.00, or 1.50 mg/kg methamphetamine. The findings from Experiment 1 showed that acquisition was delayed in rats born to lead-exposed dams gavaged daily with 16 mg lead throughout gestation and lactation when a 0.02-mg/kg/inf of methamphetamine served as the reinforcement outcome. Additional data from Experiment 2 indicated priming cues (injections of methamphetamine [i.p.]) administered after extinction were less likely to occasion a return to drug seeking (relapse) in the 16-mg group relative to the 0-mg control group. These results suggest perinatal lead exposure alters patterns of methamphetamine self-administration during the adult cycle.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Intoxicação por Chumbo/psicologia , Metanfetamina/administração & dosagem , Efeitos Tardios da Exposição Pré-Natal , Transtornos Relacionados ao Uso de Anfetaminas/sangue , Animais , Condicionamento Operante/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Chumbo/sangue , Chumbo/toxicidade , Intoxicação por Chumbo/sangue , Masculino , Gravidez , Ratos , Ratos Sprague-Dawley , Autoadministração
7.
Pharmacol Biochem Behav ; 89(4): 508-14, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18329702

RESUMO

Perinatal (gestation/lactation) lead exposure modifies the reinforcement efficacy of various psychoactive drugs (e.g., cocaine, opiates) across the phases of initial selection, use, and abuse [Nation J.R., Cardon A.L., Heard H.M., Valles R., Bratton G.R. Perinatal lead exposure and relapse to drug-seeking behavior in the rat: a cocaine reinstatement study. Psychopharmacol 2003;168: 236-243.; Nation J.R., Smith K.R., Bratton G.R. Early developmental lead exposure increases sensitivity to cocaine in a self-administration paradigm. Pharmacol Biochem Behave 2004; 77: 127-13; Rocha A., Valles R., Cardon A.L., Bratton G.R., Nation J.R. Enhanced acquisition of cocaine self-administration in rats developmentally exposed to lead. Neuropsychopharmacol 2005; 30: 2058-2064.]. However, changes in sensitivity to methamphetamine across the phases of drug abuse have not been examined in animals perinatally exposed to lead. Because the mainstream popularity of methamphetamine in the United States is increasing and lead exposure continues to be widespread, an examination of this drug and how it may be modified by perinatal exposure to lead is warranted. The studies reported here examined the effects of perinatal lead exposure on adult self-administration of intravenous (i.v.) methamphetamine across the maintenance phase of drug addiction. Experiment 1 examined dose-effect patterns in control and lead-exposed animals. Experiment 2 evaluated control and lead-exposed animals in a progressive ratio task. Female rats were administered a 16-mg lead or a control solution for 30 days prior to breeding with non-exposed males. Exposure continued through pregnancy and lactation and was discontinued at weaning (postnatal day [PND] 21). Animals born to control or lead-exposed dams received indwelling jugular catheters as adults (PND 70) and subsequently were randomly assigned to one of the two studies, using only one male rat per litter for each study. The data showed a general attenuation of the reinforcement efficacy of methamphetamine in animals perinatally exposed to lead, as compared to control animals.


Assuntos
Intoxicação do Sistema Nervoso por Chumbo/complicações , Intoxicação do Sistema Nervoso por Chumbo/psicologia , Metanfetamina/administração & dosagem , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/psicologia , Animais , Modelos Animais de Doenças , Feminino , Masculino , Motivação , Gravidez , Complicações na Gravidez/psicologia , Efeitos Tardios da Exposição Pré-Natal , Ratos , Ratos Sprague-Dawley , Reforço Psicológico , Autoadministração
8.
Pharmacol Biochem Behav ; 88(2): 165-70, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17854876

RESUMO

Conditioned place preference (CPP), a commonly used model for studying the role of contextual cues in drug reward and drug seeking, was employed to explore possible behavioral interactions between (+/-)3,4-methylenedioxymethamphetamine (MDMA; "ecstasy") and cocaine. On each of four occasions, adult male rats received one of three doses of MDMA (0 mg/kg, 5 mg/kg, 10 mg/kg; administered subcutaneously [s.c.]) combined with one of three doses of cocaine (0 mg/kg, 2.5 mg/kg, 5 mg/kg; administered intraperitoneally [i.p.]), and were then tested in a CPP paradigm. The results showed MDMA-induced CPP at a unit dose of 5 mg/kg, but at the 10 mg/kg dose there was a return to baseline (control) performance levels. For cocaine alone, CPP increased in a linear fashion as the drug dose was increased. Concurrent administration resulted in antagonism of each drug, but there was evidence that this pattern was reversible at higher doses of the respective drugs. These data are instructive insofar as they suggest that the behavioral and neurochemical effects of MDMA and cocaine presented in isolation are dramatically altered when the two drugs are presented in combination.


Assuntos
Comportamento de Escolha/efeitos dos fármacos , Cocaína/farmacologia , Condicionamento Operante/efeitos dos fármacos , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Cocaína/administração & dosagem , Relação Dose-Resposta a Droga , Interações Medicamentosas , Masculino , N-Metil-3,4-Metilenodioxianfetamina/administração & dosagem , Ratos , Ratos Sprague-Dawley , Recompensa , Serotonina/fisiologia
9.
Pharmacol Biochem Behav ; 157: 24-34, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28442368

RESUMO

Adolescence is a phase of development during which many physiological and behavioral changes occur, including increased novelty seeking and risk taking. In humans, this is reflected in experimentation with drugs. Research demonstrates that drug use that begins during adolescence is more likely to lead to addiction than drug use that begins later in life. Despite this, relatively little is known of the effects of drugs in adolescence, and differences in response between adolescents and adults. PCP and ketamine are popular club drugs, both possessing rewarding properties that could lead to escalating use. Drug sensitization (or reverse tolerance), which refers to an increase in an effect of a drug following repeated use, has been linked with the development of drug cravings that is a hallmark of addiction. The current work investigated the acute response and the development of sensitization to PCP and ketamine in adolescent and adult rats. Periadolescent Sprague-Dawley rats (30days or 38days of age), and young adults (60days of age) received PCP (6mg/kg IP) or ketamine (20mg/kg IP) once every three days, for a total of five drug injections. Adolescents and adults showed a stimulant response to the first injection of either drug, however the response was considerably greater in the youngest adolescents and lowest in the adults. With repeated administration, adults showed a robust escalation in activity that was indicative of the development of sensitization. Adolescents showed a flatter trajectory, with similar high levels of activity following an acute treatment and after five drug treatments. The results demonstrate important distinctions between adolescents and adults in the acute and repeated effects of PCP and ketamine.


Assuntos
Ketamina/administração & dosagem , Atividade Motora/efeitos dos fármacos , Movimento/efeitos dos fármacos , Fenciclidina/administração & dosagem , Fatores Etários , Anestésicos Dissociativos/administração & dosagem , Animais , Esquema de Medicação , Alucinógenos/administração & dosagem , Masculino , Atividade Motora/fisiologia , Movimento/fisiologia , Ratos , Ratos Sprague-Dawley
10.
Exp Clin Psychopharmacol ; 14(2): 245-53, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16756428

RESUMO

Partial reinforcement is known to increase resistance to extinction (Rn) relative to training with continuous reinforcement. This phenomenon, referred to as the partial reinforcement extinction effect, is one of the most robust in learning and conditioning studies. Experiment 1 investigated manipulations known to affect the partial reinforcement extinction effect and determined their possible relevance for drug use patterns. Male rats received intravenous cocaine self-administration training under partial reinforcement (FR-10) training or continuous reinforcement (FR-1) conditions with either a low (0.25 mg/kg infusion) or a high cocaine dose (1.00 mg/kg infusion). Animals were placed on an extinction (recurrent nonreward) schedule for 10 days (1-hr sessions) prior to being tested for cue-induced reinstatement (single 2-hr session). Experiment 2 involved acquisition of cocaine self-administration under FR-1 conditions of short training (15 days) or extended training (30 days) with a low dose (0.25 mg/kg infusion) or a medium dose (0.50 mg/kg infusion) of cocaine reward prior to extinction or reinstatement. Experiment 1 showed that rats trained with FR-10-high dose outcomes exhibited greater Rn than the remaining groups. Additionally, FR-10-high dose and FR-10-low dose rats were more likely to return to active drug seeking during the reinstatement test. In Experiment 2, rats trained under FR-1-medium dose conditions were more persistent during extinction following short acquisition training than comparable rats experiencing extended acquisition training. The reinstatement test was conducted following extinction, in which it was observed that overtraining under FR-1-medium dose reward schedules resulted in a decrease in the tendency to return to active drug seeking.


Assuntos
Cocaína/administração & dosagem , Extinção Psicológica , Esquema de Reforço , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Autoadministração
11.
Neuropsychopharmacology ; 30(11): 2058-64, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15827568

RESUMO

The rate of acquisition of drug self-administration may serve as a predictor of later drug-taking behavior, possibly influencing the vulnerability to use drugs. The present study examined the effects of perinatal (gestation/lactation) lead exposure on adult rates of acquisition of intravenous cocaine self-administration using an automated procedure that included both Pavlovian and operant components. For Experiment 1, female rats were gavaged daily with 0 or 16 mg lead for 30 days prior to breeding with nonexposed males. Metal administration continued through pregnancy and lactation and was discontinued at weaning (postnatal day (PND) 21). Animals born to control or lead-exposed dams subsequently were tested daily as adults in a preparation where sessions included an initial 3-h autoshaping period followed by a 3-h self-administration period where 0.20 mg/kg cocaine was delivered contingently. During autoshaping, intravenous cocaine infusions were paired with the extension and retraction of a lever, while infusions occurred during self-administration only when a lever press was executed (FR-1). The criterion for acquisition was a 2-day period during which a mean of 50 infusions/session occurred during self-administration. Animals were given 35 days to reach criterion. In Experiment 1, accelerated rates of acquisition of cocaine self-administration were evident for lead-exposed animals relative to controls. Overall, the number of self-administered cocaine infusions per session was significantly higher for lead-exposed rats as compared to control rats. Experiment 2 replicated Experiment 1 except that a higher dose of cocaine (0.80 mg/kg) was employed as the reinforcer, and 30 infusions/session was the set criterion. At the higher cocaine dose (Experiment 2), acquisition rates for control and lead-exposed animals were not markedly different, and significantly different infusion rates were not observed.


Assuntos
Anestésicos Locais/administração & dosagem , Cocaína/administração & dosagem , Condicionamento Operante/efeitos dos fármacos , Chumbo/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Animais , Animais Recém-Nascidos , Comportamento Animal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Chumbo/metabolismo , Masculino , Gravidez , Ratos , Ratos Sprague-Dawley , Esquema de Reforço , Autoadministração , Distribuição Tecidual
12.
Pharmacol Biochem Behav ; 80(4): 611-9, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15820531

RESUMO

The present investigation examined the effects of perinatal lead exposure on cocaine self-administration following a GABAA antagonist pretreatment. Female rats were exposed to either 0 or 16 mg lead daily for 30 days prior to breeding with unexposed males. Beginning on postnatal day (PND) 75, control (N=10) and lead-exposed (N=8) animals were trained to self-administer 0.50 mg/kg cocaine intravenously (IV). After stable responding was established, animals were tested at 0.03 and 0.06 mg/kg cocaine delivered intravenously (IV), combined with intraperitoneal (IP) administration of either saline, 0.50, 1.00 or 2.00 mg/kg bicuculline (a GABAA antagonist). The results showed that control animals increased self-administration responding at a cocaine dose of 0.06 mg/kg as bicuculline dose increased. Lead-exposed animals exhibited an opposite pattern, i.e., a decrease in active (cocaine) lever responding occurred as the bicuculline dose was increased. Results at the 0.03 mg/kg cocaine dose failed to show group separation, or significant changes consequent to the bicuculline pretreatment. The data suggest that GABA antagonism results in increased reward potency of a low dose of cocaine and further, that this effect is differentially expressed in animals exposed to perinatal lead.


Assuntos
Animais Recém-Nascidos/fisiologia , Bicuculina/farmacologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Antagonistas GABAérgicos/farmacologia , Antagonistas de Receptores de GABA-A , Chumbo/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Condicionamento Operante/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ratos , Ratos Sprague-Dawley , Recompensa , Autoadministração
13.
Psychopharmacology (Berl) ; 174(2): 203-10, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-14991221

RESUMO

RATIONALE: Developmental lead exposure has been found to produce differential patterns of drug self-administration in adult animals. OBJECTIVES: The present study examined the effects of perinatal (gestation/lactation) lead exposure on adult patterns of heroin self-administration. METHODS: Female rats were gavaged daily with 0 mg or 16 mg lead for 30 days prior to breeding with non-exposed males. Metal administration continued through pregnancy and lactation and was discontinued at weaning [postnatal day 21 (PND 21)]. Animals born to control or lead-exposed dams received indwelling jugular catheters as adults and were randomly assigned to one of two studies. In experiment 1, animals were tested on a FR-2 schedule in an effort to examine differential sensitivity to heroin in an intravenous self-administration paradigm. Seven doses of heroin were selected ranging from 0.56 microg/kg to 36 microg/kg per infusion. In experiment 2, littermates were tested on a progressive ratio (PR) schedule in order to more explicitly determine the nature of the change in sensitivity to the drug. RESULTS: In experiment 1, lead-exposed animals responded for heroin at significantly lower rates across most doses as evidenced by a downward shift in the inverted-U dose-effect curve. Congruent with these findings, lead-exposed animals in experiment 2 exhibited a decrease in progressive ratio responding (lower breaking points) across all heroin doses, further suggesting that perinatal lead exposure attenuates opiate self-administration in adult animals by altering the rewarding efficacy of the drug. In experiment 2, it was determined further that lead-exposed animals had lower latencies to make the initial lever press for heroin. CONCLUSIONS: These results support previous literature suggesting that perinatal exposure to inorganic lead attenuates the effectiveness of opiates as a reinforcer when animals are tested in the adult life cycle.


Assuntos
Condicionamento Operante/efeitos dos fármacos , Heroína/administração & dosagem , Chumbo/farmacologia , Troca Materno-Fetal , Autoadministração , Animais , Peso Corporal/efeitos dos fármacos , Feminino , Infusões Intravenosas , Chumbo/sangue , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ratos , Ratos Sprague-Dawley
14.
Neurotoxicology ; 25(5): 869-75, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15288517

RESUMO

This investigation examined the effects of perinatal cadmium exposure on subsequent self-administration of cocaine during the adult cycle. Female Sprague-Dawley rats were gavaged daily with 0.0 (14% sucrose solution, w/v) or 5.0 mg cadmium chloride (dissolved in 14% sucrose solution, w/v) for 30 days prior to breeding with non-exposed males. Dams continued to experience cadmium exposure through gestation and until pups were weaned at postnatal day (PND) 21. On PND 70, offspring were anesthetized and chronic indwelling jugular catheters were implanted. Following recovery, test subjects were trained in operant chambers to self-administer 0.500 mg/kg infusion (inf) intravenous cocaine on a fixed-ratio (FR) 2 schedule of reinforcement. Following acquisition, self-administration rates were tested for saline, 0.030, 0.060, 0.125, 0.250, and 0.500 mg/kg inf cocaine. Rats exposed developmentally to cadmium self-administered significantly less than controls at saline, 0.030, and 0.060 mg/kg inf cocaine. These data indicate that early-life cadmium exposure, a common exposure vector of which is the use of tobacco products, may affect cocaine sensitivity.


Assuntos
Intoxicação por Cádmio/psicologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Lactação/fisiologia , Efeitos Tardios da Exposição Pré-Natal , Animais , Peso Corporal/efeitos dos fármacos , Condicionamento Operante , Relação Dose-Resposta a Droga , Feminino , Gravidez , Ratos , Ratos Sprague-Dawley , Esquema de Reforço , Autoadministração/psicologia
15.
An Bras Dermatol ; 87(3): 491-2, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22714774

RESUMO

An 80-year-old Caucasian male patient was referred for evaluation of a rapidly growing, asymptomatic, erythematous nodule measuring 2 cm in diameter on his left cheek. The lesion had been present for four months. Dermoscopy revealed a homogeneous pink background with polymorphous telangiectatic vessels. Histopathology showed tumors in the deep dermis and subcutis composed of round cells with scant cytoplasm. Immunohistochemical staining was positive for CK20 confirming the diagnosis of Merkel cell carcinoma.


Assuntos
Carcinoma de Célula de Merkel/patologia , Neoplasias Faciais/patologia , Neoplasias Cutâneas/patologia , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Bochecha , Humanos , Queratina-20/análise , Masculino
16.
An. bras. dermatol ; 87(3): 491-492, May-June 2012. ilus
Artigo em Inglês | LILACS | ID: lil-638548

RESUMO

An 80-year-old Caucasian male patient was referred for evaluation of a rapidly growing, asymptomatic, erythematous nodule measuring 2 cm in diameter on his left cheek. The lesion had been present for four months. Dermoscopy revealed a homogeneous pink background with polymorphous telangiectatic vessels. Histopathology showed tumors in the deep dermis and subcutis composed of round cells with scant cytoplasm. Immunohistochemical staining was positive for CK20 confirming the diagnosis of Merkel cell carcinoma.


Paciente de 80 anos, branco, sexo masculino, encaminhado para avaliação de nódulo eritematoso de 2 cm, assintomático, de crescimento rápido, localizado na região malar esquerda, com quatro meses de evolução. À dermatoscopia visualizou-se fundo homogêneo róseo com telangiectasias polimorfas. O exame anatomopatológico revelou massas tumorais atingindo a derme profunda e o subcutâneo, compostas por células arredondadas, de citoplasma escasso. A imunohistoquímica foi positiva para CK20, confirmando o diagnóstico de carcinoma de células de Merkel.


Assuntos
Idoso de 80 Anos ou mais , Humanos , Masculino , Carcinoma de Célula de Merkel/patologia , Neoplasias Faciais/patologia , Neoplasias Cutâneas/patologia , Bochecha , /análise , Biomarcadores Tumorais/análise
17.
Rio de Janeiro; s.n; 2015. ix,87 p. tab, graf.
Tese em Português | TESESFIO, FIOCRUZ | ID: tes-6250

RESUMO

A regulação assistencial adequada melhora a equidade no acesso à atenção especializada conforme a necessidade das pessoas, tornando-se um instrumento para a garantia da atenção integral. A crescente regulamentação do SUS responsabilizou os municípios pela regulação assistencial para garantir a integralidade e o adequado funcionamento das redes de atenção à saúde. O município do Rio de Janeiro, após diferentes configurações, passou a regular as vagas de procedimentos especializado através da plataforma web SISREG, desenvolvida pelo DATASUS. Em junho de 2012, a gestão municipal descentralizou a regulação ambulatorial e empoderou os médicos responsáveis técnicos das unidades básicas de saúde para exercer tal função. O presente estudo objetivou analisar os efeitos da inserção dos profissionais da Atenção Primária à Saúde no processo de regulação assistencial ambulatorial no município do Rio de Janeiro, RJ na qualidade da regulação e nas filas de espera. Quatro procedimentos foram analisados, tomados como marcadores: consulta em oftalmologia geral-geral, consulta em cirurgia geral-geral, consulta em obstetrícia alto risco geral e mamografia bilateral- rastreamento. A partir de dados do SISREG foram comparados número de vagas, status das solicitações, tempo médio de espera geral e de acordo com a classificação de risco dos quatro procedimentos, entre janeiro de 2011 e dezembro de 2013. (...)


Com base na literatura e a partir da análise dos dados, conclui-se que a redução dos tempos de espera resultaram de um conjunto diversificado de medidas tomadas pela SMS do Rio de Janeiro. As mudanças na regulação melhoraram sua qualidade e foram mais efetivas para redução de tempos de espera quando acompanhadas do aumento da oferta de vagas. É necessário buscar novas perspectivas de responsabilização da APS e de aproximação dos prestadores dos diversos níveis para a coordenação do cuidado de modo que a regulação assistencial torne-se um instrumento de melhoria da equidade e não mais uma barreira ao acesso dos usuários. (AU)


An adequate healthcare regulation improves the equity to the access to the specialized care according to the person needs, and became a tool to assure an access to a comprehensive health care. The increasing regulation of the Brazilian Unified Health System (hereby SUS) passed the responsibility to the municipalities for the healthcare regulation to assure the comprehensiveness and the adequate operation of the healthcare network. Rio de Janeiro city, after several configuration attempts, began to regulate the specialized procedures through the web SISREG platform, developed by DATASUS. In June 2012, the municipal management decentralized the outpatient regulation and empowered doctors that were technical managers of the basic health care units to serve as refugators. (...) The quality of the regulation presented improvement for the four precedures, with the increase in the returned and denied requisitions, showing a more careful evaluation from the managers. From the data analysis, based on the literature, it can be concluded that the set of measurements taken by the Rio Janeiros SMS incurred in the reduction of the average waiting time, and that increase of the number of schedule is one of the most effective measurement. It is necessary to search for new perspectives for the accountability of APS and the oncoming of the providers of several levels to coordinate the care in a way the healthcare regulation became a tool for the improvement in the equity and not another barrier to the access of the users. (AU)


Assuntos
Humanos , Assistência Ambulatorial , Regulação e Fiscalização em Saúde , Atenção Primária à Saúde , Listas de Espera , Assistência Integral à Saúde
18.
Tese em Português | ARCA | ID: arc-14196

RESUMO

A regulação assistencial adequada melhora a equidade no acesso à atenção especializada conforme a necessidade das pessoas, tornando-se um instrumento para a garantia da atenção integral. A crescente regulamentação do SUS responsabilizou os municípios pela regulação assistencial para garantir a integralidade e o adequado funcionamento das redes de atenção à saúde. O município do Rio de Janeiro, após diferentes configurações, passou a regular as vagas de procedimentos especializado através da plataforma web SISREG, desenvolvida pelo DATASUS. Em junho de 2012, a gestão municipal descentralizou a regulação ambulatorial e empoderou os médicos responsáveis técnicos das unidades básicas de saúde para exercer tal função. O presente estudo objetivou analisar os efeitos da inserção dos profissionais da Atenção Primária à Saúde no processo de regulação assistencial ambulatorial no município do Rio de Janeiro, RJ na qualidade da regulação e nas filas de espera. Quatro procedimentos foram analisados, tomados como marcadores: consulta em oftalmologia geral-geral, consulta em cirurgia geral-geral, consulta em obstetrícia alto risco geral e mamografia bilateral- rastreamento. A partir de dados do SISREG foram comparados número de vagas, status das solicitações, tempo médio de espera geral e de acordo com a classificação de risco dos quatro procedimentos, entre janeiro de 2011 e dezembro de 2013. (...) Com base na literatura e a partir da análise dos dados, conclui-se que a redução dos tempos de espera resultaram de um conjunto diversificado de medidas tomadas pela SMS do Rio de Janeiro. As mudanças na regulação melhoraram sua qualidade e foram mais efetivas para redução de tempos de espera quando acompanhadas do aumento da oferta de vagas. É necessário buscar novas perspectivas de responsabilização da APS e de aproximação dos prestadores dos diversos níveis para a coordenação do cuidado de modo que a regulação assistencial torne-se um instrumento de melhoria da equidade e não mais uma barreira ao acesso dos usuários.


Assuntos
Assistência Ambulatorial , Regulação e Fiscalização em Saúde , Atenção Primária à Saúde , Listas de Espera , Assistência Integral à Saúde
19.
Rio de Janeiro; s.n; 2015. ix,87 p. tab, graf.
Tese em Português | ENSP, FIOCRUZ | ID: ens-37491

RESUMO

A regulação assistencial adequada melhora a equidade no acesso à atenção especializada conforme a necessidade das pessoas, tornando-se um instrumento para a“ Só eu sei as esquinas por que passei …viigarantia da atenção integral. A crescente regulamentação do SUS responsabilizou os municípios pela regulação assistencial para garantir a integralidade e o adequado funcionamento das redes de atenção à saúde. O município do Rio de Janeiro, após diferentes configurações, passou a regular as vagas de procedimentos especializado através da plataforma web SISREG, desenvolvida pelo DATASUS. Em junho de 2012, a gestão municipal descentralizou a regulação ambulatorial e empoderou os médicos responsáveis técnicos das unidades básicas de saúde para exercer tal função. O presente estudo objetivou analisar os efeitos da inserção dos profissionais da Atenção Primária à Saúde no processo de regulação assistencial ambulatorial no município do Rio de Janeiro-RJ na qualidade da regulação e nas filas de espera. Quatro procedimentos foram analisados, tomados como marcadores: consulta em oftalmologia geral-geral, consulta em cirurgia geral-geral, consulta em obstetrícia alto risco geral e mamografia bilateral- rastreamento. A partir de dados do SISREG foram comparados número de vagas, status das solicitações, tempo médio de espera geral e de acordo com a classificação de risco dos quatro procedimentos, entre janeiro de 2011 e dezembro de 2013. Os resultados mostram efeitos diferenciados por procedimento. Para consulta em oftalmologia, o número de vagas dobrou ao longo do período e houve redução do tempo de espera em 50%, de 184 dias em 2011 para 99 dias em 2013. Para consulta em cirurgia geral o aumento do número de vagas foi de apenas 6% e o tempo de espera subiu de 63 para 72 dias.


Para consulta de obstetrícia-alto risco ocorreu aumento do número de vagas e o tempo de espera reduziu para as classificações de risco mais graves (risco vermelho, de 38 para 25 dias), porém observou-se leve aumento no tempo médio de espera, de 36 para 39 dias. Para mamografia rastreamento que tem oferta de vagas suficiente ocorreu redução do tempo de espera (de 68 para 18 dias) bem como do absenteísmo. A qualidade da regulação para os quatro procedimentos melhorou com o aumento de solicitações devolvidas e negadas, demonstrando avaliação mais criteriosa pelos reguladores. Com base na literatura e a partir da análise dos dados, conclui-se que a redução dos tempos de espera resultaram de um conjunto diversificado de medidas tomadas pela SMS do Rio de Janeiro. As mudanças na regulação melhoraram sua qualidade e foram mais efetivas para redução de tempos de espera quando acompanhadas do aumento da oferta de vagas. É necessário buscar novas perspectivas de responsabilização da APS e de aproximação dos prestadores dos diversos níveis para a coordenação do cuidado de modo que a regulação assistencial torne-se um instrumento de melhoria da equidade e não mais uma barreira ao acesso dos usuários. (AU)


An adequate healthcare regulation improves the equity to the access to the specialized care according to the person needs, and became a tool to assure an access to a comprehensive health care. The increasing regulation of the Brazilian Unified Health System (hereby SUS) passed the responsibility to the municipalities for the healthcare regulation to assure the comprehensiveness and the adequate operation of the healthcare network. Rio de Janeiro city, after several configuration attempts, began to regulate the specialized procedures through the web SISREG platform, developed by DATASUS. In June 2012, the municipal management decentralized the outpatient regulation and empowered doctors that were technical managers of the basic health care units to serve as refugators. The present study has as objective to analyse the effects of the insertion of the primary health care professionals in the regulation process of outpatient specialized care in the municipality of Rio de Janeiro-RJ, regarding qualify of regulation and waiting times. Four procedures were analysed: consultations in ophthalmology, consultations in general surgery, consultations in obstetrics and consultations for screening bilateral mammogram. Based of the data from SISREG, it was possible to compare the number of schedule, requisition status, the overall average waiting times and according to the risk rating in these four procedures, between January 2011 and December 2013. The main findings were: the amount of schedule for ophthalmology doubled in the period and occur a reduction in almost 50% in the waiting times; for surgery the waiting times increased in 10 days over time, and the number of consultation increased in 6% between the period; for obstetrics the waiting times were reduced for the most severe classification risks, however it was observed a slight increase in the average waiting times; for screening bilateral mammogram there was a reduction in wait time as well as absenteeism.


The quality of the regulation presented improvement for the four precedures, with the increase in the returned and denied requisitions, showing a more careful evaluation from the managers. From the data analysis, based on the literature, it can be concluded that the set of measurements taken by the Rio Janeiros´s SMS incurred in the reduction of the average waiting time, and that increase of the number of schedule is one of the most effective measurement. It is necessary to search for new perspectives for the accountability of APS and the oncoming of the providers of several levels to coordinate the care in a way the healthcare regulation became a tool for the improvement in the equity and not another barrier to the access of the users. (AU)


Assuntos
Humanos , Assistência Ambulatorial , Regulação e Fiscalização em Saúde , Atenção Primária à Saúde , Listas de Espera , Assistência Integral à Saúde , Análise de Dados
20.
Rev. gerenc. políticas salud ; 5(11): 70-95, dic. 2006. tab, graf
Artigo em Espanhol | LILACS | ID: lil-582135

RESUMO

La evaluación de eficiencia para los hospitales públicos a nivel nacional se hace bajo la premisa de que la unidad hospitalaria es parte del sistema general de salud y en particular de la red de atención. La eficiencia se mide desde dos perspectivas, la primera la dada por los indicadores de recursos, aprovechamiento, funcionamiento y calidad; y la segunda perspectiva es la dada por un modelo de frontera estocástica. Los resultados indican que los hospitales públicos de segundo y tercer nivel, así como los centros de salud, son eficientes técnicamente, mientras que en los hospitales de primer nivel se evidencia un comportamiento ineficiente desde el punto de vista técnico, y la evidencia indica que esta ineficiencia es un problema de las unidades en el sistema, donde el componente del sistema refiere a una inadecuada asignación de recursos.


The evaluation of the efficiency of public hospitals at national level is done under the assumption that the country has a general health system, and the hospitals belongs to this system, especiallybelongs to safety public health net. The efficiency is measure in two paths, the first given by the indicators of use, resources, functioning and quality. The second way is given by the adjustmentof the stochastic frontier. The results show that the public hospitals in second and third level, and primary health attention centers are efficient technically, while the evidence say that the first level public hospitals are inefficient like units, in the sense of technical use of the raw materials - technically inefficient -, and the exploratory analysis show that inefficient occurs because there are anot optimum assignation of resources, and according to the law this assignation is not a function of the hospital, it is a function of the system.


Assuntos
Indicadores Básicos de Saúde , Administração de Recursos Humanos em Hospitais
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