RESUMO
The probability of suffering the mood disorder depression is up to 30% in women and 15% in men during their life span. Pharmacological options for depression are limited: conventional antidepressants have low efficacy and a delayed onset of action (several weeks). Here we investigate the antidepressant actions of inhibitors of monoacylglycerol lipase (MAGL), the major degradative enzyme of the endocannabinoid 2-arachidonoylglycerol. A low-dose of MAGL inhibitors produces antidepressant effects on acute stress-exposed mice, through glutamatergic synaptic long-term depression (LTD), without significant effects on chronic corticosterone-exposed mice. In contrast, a high-dose of MAGL inhibitors produces pro- or antidepressant effects on acute stress- or chronic corticosterone-exposed mice, respectively, through GABAergic synaptic disinhibition. In the hippocampus, in vivo inhibition of MAGL induces a CB1 cannabinoid receptor (CB1R)-dependent suppression of inhibitory GABAergic synapses and an in vivo LTD of excitatory glutamatergic synapses. LTD induction requires CB1R in astroglial cells (but not in GABAergic or glutamatergic neurons) and postsynaptic glutamate receptors. The conventional antidepressant fluoxetine produces rapid or delayed antidepressant effects in acute stress- or chronic corticosterone-exposed mice, respectively. We propose that depression-like behavior of animals in response to acute stress is the normal behavioral response, and thus, MAGL inhibitors, which produce antidepressant effects in chronic corticosterone-exposed animals through GABAergic synaptic disinhibition, represent a new class of rapidly-acting and long-lasting antidepressants.
Assuntos
Benzodioxóis/metabolismo , Depressão/metabolismo , Piperidinas/metabolismo , Animais , Antidepressivos/farmacologia , Ácidos Araquidônicos , Benzodioxóis/uso terapêutico , Região CA1 Hipocampal/metabolismo , Depressão/tratamento farmacológico , Endocanabinoides/metabolismo , Endocanabinoides/uso terapêutico , Neurônios GABAérgicos/metabolismo , Hipocampo/metabolismo , Depressão Sináptica de Longo Prazo/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Monoacilglicerol Lipases/antagonistas & inibidores , Monoacilglicerol Lipases/metabolismo , Neurônios/metabolismo , Piperidinas/uso terapêutico , Receptor CB1 de Canabinoide/metabolismo , Sinapses/metabolismoRESUMO
A large body of evidence has been brought forward connecting developmental immune activation to abnormal fear and anxiety levels. Anxiety disorders have extremely high lifetime prevalence, yet susceptibility factors that contribute to their emergence are poorly understood. In this research we investigated whether an inflammatory insult early in life can alter the response to fear conditioning in adulthood. Fear learning and extinction are important and adaptive behaviors, mediated largely by the amygdala and its interconnectivity with cortico-limbic circuits. Male and female rat pups were given LPS (100µg/kg i.p.) or saline at postnatal day 14; LPS activated cFos expression in the central amygdala 2.5h after exposure, but not the basal or lateral nuclei. When tested in adulthood, acquisition of an auditory cued or contextual learned fear memory was largely unaffected as was the extinction of fear to a conditioned context. However, we detected a deficit in auditory fear extinction in male and female rats that experienced early-life inflammation, such that there is a significant delay in fear extinction processes resulting in more sustained fear behaviors in response to a conditioned cue. This response was specific to extinction training and did not persist into extinction recall. The effect could not be explained by differences in pain threshold (unaltered) or in baseline anxiety, which was elevated in adolescent females only and unaltered in adolescent males and adult males and females. This research provides further evidence for the involvement of the immune system during development in the shaping of fear and anxiety related behaviors.
Assuntos
Extinção Psicológica/efeitos dos fármacos , Medo/fisiologia , Estresse Psicológico/imunologia , Adaptação Psicológica , Tonsila do Cerebelo/efeitos dos fármacos , Animais , Ansiedade/metabolismo , Transtornos de Ansiedade , Condicionamento Clássico/fisiologia , Condicionamento Psicológico/fisiologia , Sinais (Psicologia) , Feminino , Inflamação , Aprendizagem , Lipopolissacarídeos/farmacologia , Masculino , Rememoração Mental/fisiologia , Ratos , Ratos Sprague-Dawley , RoedoresRESUMO
Early-life inflammation has been shown to exert profound effects on brain development and behavior, including altered emotional behavior, stress responsivity and neurochemical/neuropeptide receptor expression and function. The current study extends this research by examining the impact of inflammation, triggered with the bacterial compound lipopolysaccharide (LPS) on postnatal day (P) 14, on social behavior during adolescence. We investigated the role that the endocannabinoid (eCB) system plays in sociability after early-life LPS. To test this, multiple cohorts of Sprague Dawley rats were injected with LPS on P14. In adolescence, rats were subjected to behavioral testing in a reciprocal social interaction paradigm as well as the open field. We quantified eCB levels in the amygdala of P14 and adolescent animals (anandamide and 2-arachidonoylglycerol) as well as adolescent amygdaloid cannabinoid receptor 1 (CB1) binding site density and the hydrolytic activity of the enzyme fatty acid amide hydrolase (FAAH), which metabolizes the eCB anandamide. Additionally, we examined the impact of FAAH inhibition on alterations in social behavior. Our results indicate that P14 LPS decreases adolescent social behavior (play and social non-play) in males and females at P40. This behavioral alteration is accompanied by decreased CB1 binding, increased anandamide levels and increased FAAH activity. Oral administration of the FAAH inhibitor PF-04457845 (1mg/kg) prior to the social interaction task normalizes LPS-induced alterations in social behavior, while not affecting social behavior in the control group. Infusion of 10ng PF-04457845 into the basolateral amygdala normalized social behavior in LPS injected females. These data suggest that alterations in eCB signaling following postnatal inflammation contribute to impairments in social behavior during adolescence and that inhibition of FAAH could be a novel target for disorders involving social deficits such as social anxiety disorders or autism.
Assuntos
Tonsila do Cerebelo/metabolismo , Ácidos Araquidônicos/metabolismo , Comportamento Animal , Endocanabinoides/metabolismo , Inflamação/psicologia , Alcamidas Poli-Insaturadas/metabolismo , Comportamento Social , Amidoidrolases/antagonistas & inibidores , Amidoidrolases/metabolismo , Animais , Feminino , Glicerídeos/metabolismo , Inflamação/induzido quimicamente , Lipopolissacarídeos , Masculino , Piridazinas/administração & dosagem , Ratos Sprague-Dawley , Receptor CB1 de Canabinoide/metabolismo , Transdução de Sinais , Ureia/administração & dosagem , Ureia/análogos & derivadosRESUMO
Hyperactivation of the amygdala following chronic stress is believed to be one of the primary mechanisms underlying the increased propensity for anxiety-like behaviors and pathological states; however, the mechanisms by which chronic stress modulates amygdalar function are not well characterized. The aim of the current study was to determine the extent to which the endocannabinoid (eCB) system, which is known to regulate emotional behavior and neuroplasticity, contributes to changes in amygdalar structure and function following chronic stress. To examine the hypothesis, we have exposed C57/Bl6 mice to chronic restraint stress, which results in an increase in fatty acid amide hydrolase (FAAH) activity and a reduction in the concentration of the eCB N-arachidonylethanolamine (AEA) within the amygdala. Chronic restraint stress also increased dendritic arborization, complexity and spine density of pyramidal neurons in the basolateral nucleus of the amygdala (BLA) and increased anxiety-like behavior in wild-type mice. All of the stress-induced changes in amygdalar structure and function were absent in mice deficient in FAAH. Further, the anti-anxiety effect of FAAH deletion was recapitulated in rats treated orally with a novel pharmacological inhibitor of FAAH, JNJ5003 (50 mg per kg per day), during exposure to chronic stress. These studies suggest that FAAH is required for chronic stress to induce hyperactivity and structural remodeling of the amygdala. Collectively, these studies indicate that FAAH-mediated decreases in AEA occur following chronic stress and that this loss of AEA signaling is functionally relevant to the effects of chronic stress. These data support the hypothesis that inhibition of FAAH has therapeutic potential in the treatment of anxiety disorders, possibly by maintaining normal amygdalar function in the face of chronic stress.
Assuntos
Amidoidrolases/antagonistas & inibidores , Amidoidrolases/fisiologia , Tonsila do Cerebelo/patologia , Ansiedade/prevenção & controle , Estresse Psicológico/enzimologia , Amidoidrolases/deficiência , Amidoidrolases/genética , Tonsila do Cerebelo/metabolismo , Animais , Ansiedade/enzimologia , Ansiedade/etiologia , Ácidos Araquidônicos , Doença Crônica , Cicloexanóis/farmacologia , Dendritos/ultraestrutura , Avaliação Pré-Clínica de Medicamentos , Endocanabinoides/deficiência , Endocanabinoides/metabolismo , Comportamento Exploratório/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Alcamidas Poli-Insaturadas , Células Piramidais/patologia , Ratos , Ratos Sprague-Dawley , Receptor CB1 de Canabinoide/agonistas , Receptor CB1 de Canabinoide/fisiologia , Restrição Física/efeitos adversos , Estresse Psicológico/complicações , Estresse Psicológico/patologia , Estresse Psicológico/fisiopatologiaRESUMO
Neural activity within the ventromedial prefrontal cortex (vmPFC) is a critical determinant of stressor-induced anxiety. Pharmacological activation of the vmPFC during stress protects against stress-induced social anxiety suggesting that altering the excitatory/inhibitory (E/I) tone in the vmPFC may promote stress resilience. E/I balance is maintained, in part, by endogenous cannabinoid (eCB) signaling with the calcium dependent retrograde release of 2-arachidonoylglycerol (2-AG) suppressing presynaptic neurotransmitter release. We hypothesized that raising 2-AG levels, via inhibition of its degradation enzyme monoacylglycerol lipase (MAGL) with KML29, would shift vmPFC E/I balance and promote resilience. In acute slice experiments, bath application of KML29 (100 nM) augmented evoked excitatory neurotransmission as evidenced by a left-shift in fEPSP I/O curve, and decreased sIPSC amplitude. In whole-cell recordings, KML29 increased resting membrane potential but reduced the after depolarization, bursting rate, membrane time constant and slow after hyperpolarization. Intra-vmPFC administration of KML29 (200ng/0.5µL/hemisphere) prior to inescapable stress (IS) exposure (25, 5s tail shocks) prevented stress induced anxiety as measured by juvenile social exploration 24 h after stressor exposure. Conversely, systemic administration of KML29 (40 mg/kg, i.p.) 2 h before IS exacerbated stress induced anxiety. MAGL inhibition in the vmPFC may promote resilience by augmenting the output of neurons that project to brainstem and limbic structures that mediate stress responses.
Assuntos
Potenciais Pós-Sinápticos Excitadores/fisiologia , Monoacilglicerol Lipases/antagonistas & inibidores , Monoacilglicerol Lipases/metabolismo , Córtex Pré-Frontal/enzimologia , Estresse Psicológico/enzimologia , Estresse Psicológico/psicologia , Animais , Benzodioxóis/farmacologia , Benzodioxóis/uso terapêutico , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Masculino , Técnicas de Cultura de Órgãos , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Córtex Pré-Frontal/efeitos dos fármacos , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Ratos , Ratos Endogâmicos F344 , Estresse Psicológico/tratamento farmacológicoRESUMO
The developing brain undergoes substantial maturation into adulthood and the development of specific neural structures occurs on differing timelines. Transient imbalances between developmental trajectories of corticolimbic structures, which are known to contribute to regulation over fear learning and anxiety, can leave an individual susceptible to mental illness, particularly anxiety disorders. There is a substantial body of literature indicating that the endocannabinoid (eCB) system critically regulates stress responsivity and emotional behavior throughout the life span, making this system a novel therapeutic target for stress- and anxiety-related disorders. During early life and adolescence, corticolimbic eCB signaling changes dynamically and coincides with different sensitive periods of fear learning, suggesting that eCB signaling underlies age-specific fear learning responses. Moreover, perturbations to these normative fluctuations in corticolimbic eCB signaling, such as stress or cannabinoid exposure, could serve as a neural substrate contributing to alterations to the normative developmental trajectory of neural structures governing emotional behavior and fear learning. In this review, we first introduce the components of the eCB system and discuss clinical and rodent models showing eCB regulation of fear learning and anxiety in adulthood. Next, we highlight distinct fear learning and regulation profiles throughout development and discuss the ontogeny of the eCB system in the central nervous system, and models of pharmacological augmentation of eCB signaling during development in the context of fear learning and anxiety.
Assuntos
Ansiedade/metabolismo , Encéfalo/crescimento & desenvolvimento , Endocanabinoides/metabolismo , Medo , Aprendizagem , Animais , Encéfalo/metabolismo , Encéfalo/fisiologia , Humanos , NeurogêneseRESUMO
UNLABELLED: Women of child-bearing age are the population group at highest risk for depression. In pregnant women, fluoxetine (Flx) is the most widely prescribed selective serotonin reuptake inhibitor (SSRI) used for the treatment of depression. While maternal stress, depression, and Flx exposure have been shown to effect neurodevelopment of the offspring, separately, combined effects of maternal stress and Flx exposure have not been extensively examined. The present study investigated the effects of prenatal maternal stress and perinatal exposure to the SSRI Flx on the behavior of male mice as adults. METHODS: C57BL/6 dams exposed to chronic unpredictable stress from embryonic (E) day 4 to E18 and non-stressed dams were administered Flx (25 mg/kg/d) in the drinking water from E15 to postnatal day 12. A separate control group consisted of animals that were not exposed to stress or Flx. At 12 days of age, brain levels of serotonin were assessed in the male offspring. At two months of age, the male offspring of mothers exposed to prenatal stress (PS), perinatal Flx, PS and Flx, or neither PS or Flx, went through a comprehensive behavioral test battery. At the end of testing brain-derived neurotropic factor (BDNF) levels were assessed in the frontal cortex of the offspring. RESULTS: Maternal behavior was not altered by either stress or Flx treatment. Treatment of the mother with Flx led to detectible Flx and NorFlx levels and lead to a decrease in serotonin levels in pup brains. In the adult male offspring, while perinatal exposure to Flx increased aggressive behavior, prenatal maternal stress decreased aggressive behavior. Interestingly, the combined effects of stress and Flx normalized aggressive behavior. Furthermore, perinatal Flx treatment led to a decrease in anxiety-like behavior in male offspring. PS led to hyperactivity and a decrease in BDNF levels in the frontal cortex regardless of Flx exposure. Neither maternal stress or Flx altered offspring performance in tests of cognitive abilities, memory, sensorimotor information processing, or risk assessment behaviors. These results demonstrate that maternal exposure to stress and Flx have a number of sustained effects on the male offspring.
Assuntos
Comportamento Animal , Encéfalo/efeitos dos fármacos , Fluoxetina/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Inibidores Seletivos de Recaptação de Serotonina/toxicidade , Estresse Psicológico , Agressão/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Masculino , Comportamento Materno/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , GravidezRESUMO
It has previously been shown in rats that acute administration of delta-9-tetrahydrocannabinol (THC) exerts a dose-dependent effect on simple locomotor activity, with low doses of THC causing hyper-locomotion and high doses causing hypo-locomotion. However the effect of acute THC administration on cortical movement representations (motor maps) and skilled learned movements is completely unknown. It is important to determine the effects of THC on motor maps and skilled learned behaviors because behaviors like driving place people at a heightened risk. Three doses of THC were used in the current study: 0.2mg/kg, 1.0mg/kg and 2.5mg/kg representing the approximate range of the low to high levels of available THC one would consume from recreational use of cannabis. Acute peripheral administration of THC to drug naïve rats resulted in dose-dependent alterations in motor map expression using high resolution short duration intracortical microstimulation (SD-ICMS). THC at 0.2mg/kg decreased movement thresholds and increased motor map size, while 1.0mg/kg had the opposite effect, and 2.5mg/kg had an even more dramatic effect. Deriving complex movement maps using long duration (LD)-ICMS at 1.0mg/kg resulted in fewer complex movements. Dosages of 1.0mg/kg and 2.5mg/kg THC reduced the number of reach attempts but did not affect percentage of success or the kinetics of reaching on the single pellet skilled reaching task. Rats that received 2.5mg/kg THC did show an increase in latency of forelimb removal on the bar task, while dose-dependent effects of THC on unskilled locomotor activity using the rotorod and horizontal ladder tasks were not observed. Rats may be employing compensatory strategies after receiving THC, which may account for the robust changes in motor map expression but moderate effects on behavior.
Assuntos
Dronabinol/farmacologia , Atividade Motora/efeitos dos fármacos , Córtex Motor/efeitos dos fármacos , Psicotrópicos/farmacologia , Animais , Estimulação Elétrica , Membro Anterior , Masculino , Ratos , Ratos Long-EvansRESUMO
BACKGROUND: Oxygen (O(2)) homeostasis is central to myocardial tissue functioning, and increased O(2) demand is thought to be satisfied by a vasodilatory mechanism that results in increased blood and O(2) delivery. We applied blood oxygenation level-dependent (BOLD) MRI in conjunction with vasodilatory stress to index the ability to augment intramyocardial oxygenation in hypertensive hypertrophy, the primary cause of heart failure. METHODS AND RESULTS: Nine healthy controls and 10 hypertensive subjects with moderate-to-severe hypertrophy underwent imaging on a 1.5 T clinical scanner. The dipyridamole-induced change in the apparent transverse relaxation rate, R2*, which correlates with hemoglobin oxygenation, was -5.4+/-2.2 s(-1) (95% CI, -4.0 to -6.8 s(-1)) in controls compared with -1.7+/-1.4 s(-1) (95% CI, -0.8 to -2.6 s(-1)) in hypertensive patients (P=0.0003). CONCLUSIONS: Patients with hypertensive hypertrophy demonstrate an impaired ability to increase intramyocardial oxygenation during vasodilatory stress, as indexed by BOLD MRI. The capacity to image vascular function with BOLD MRI may advance the understanding of the development of ventricular dysfunction in hypertension.
Assuntos
Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Oxigênio/sangue , Vasodilatação , Adulto , Circulação Coronária/efeitos dos fármacos , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/fisiopatologia , Dipiridamol/administração & dosagem , Feminino , Humanos , Hipertensão/sangue , Hipertensão/complicações , Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/etiologia , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Vasodilatação/efeitos dos fármacos , Vasodilatadores/administração & dosagemRESUMO
To determine the extent to which the Fifth Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC-V) guidelines were implemented in high-risk families with premature coronary heart disease, we examined the prevalence of hypertension and associated coronary risk factors in asymptomatic siblings of persons with documented premature coronary disease (<60 years of age). A total of 859 apparently healthy siblings (51% male, 19% African American) were screened for coronary risk factors. Siblings were classified as normotensive or hypertensive (BP > or = 140/90 and/or current antihypertensive pharmacotherapy). The prevalence of hypertension, awareness, treatment, and control among siblings was compared with published national estimates from the third National Health and Nutrition Examination Survey. The prevalence of hypertension in siblings was 44%. Among all hypertensives, only 60% were aware of being hypertensive, 45% were being treated, and 16% were under control. A high prevalence of other coronary risk factors was found among hypertensive siblings: 72% were hypercholesterolemic; 61% were obese; 29% were current smokers; 82% were consuming >30% of calories from fat; and only 14% were participating in vigorous physical activity three or more times per week. Comparisons with the national reference population revealed siblings to have a significantly higher prevalence of hypertension, along with significantly lower levels of awareness, treatment, and control. These findings demonstrate the intersection of multiple risk factors among hypertensive siblings and emphasize the need for more aggressive screening and treatment in this easily identifiable high-risk population.
Assuntos
Pressão Sanguínea , Doença das Coronárias/etiologia , Hipertensão/epidemiologia , Adulto , Fatores Etários , Conscientização , População Negra , Colesterol/sangue , Saúde da Família , Feminino , Humanos , Hipertensão/prevenção & controle , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Esforço Físico , Prevalência , Fatores de Risco , Fatores Sexuais , População BrancaRESUMO
The objective of this study was to determine the prevalence of symptoms and the morbidity associated with Raynaud's phenomenon (RP) among African Americans. A total of 2196 randomly selected residents of an inner-city community, in Baltimore, completed a health-assessment survey. Symptoms of RP consisted of cold sensitivity plus cold-induced white or blue digital color change. One third (n = 703) reported cold sensitivity and 14% (n = 308) reported digital color change; 84 residents with symptoms of RP were identified, yielding an overall prevalence rate of 3.8% (95% confidence interval [CI] 3.0-4.6). RP was associated with poor or fair health status (odds ratio [OR] = 1.82, CI 1.18-2.81), heart disease (OR = 2.32, CI 1.39-3.87), and stroke (OR = 2.20, CI 1.17-4.15), after adjustment for age, gender, and physician-diagnosed arthritis. The prevalence of symptoms of RP in this African-American community is comparable to published reports from other populations. These community-based data suggest that identification of RP among African Americans should raise consideration of possible comorbidity, particularly cardiovascular disease.
Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Doença de Raynaud/complicações , Doença de Raynaud/epidemiologia , Saúde da População Urbana/estatística & dados numéricos , Adulto , Baltimore/epidemiologia , Temperatura Baixa/efeitos adversos , Estudos Transversais , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Doença de Raynaud/diagnósticoRESUMO
Barriers to high blood pressure (HBP) care and control have been reported in the literature for > 30 years. Few reports on barriers, however, have focused on the young black man with HBP, the age/sex/race group with the highest rates of early severe and complicated HBP and the lowest rates of awareness, treatment, and control. In a randomized clinical trial of comprehensive care for hypertensive young urban black men, factors potentially associated with care and control were assessed at baseline for the 309 enrolled men. A majority of the men encountered a variety of barriers including economic, social, and lifestyle obstacles to adequate BP care and control, including no current HBP care (49%), risk of alcoholism (62%), use of illicit drugs (45%), social isolation (47%), unemployment (40%), and lack of health insurance (51%). Having health insurance (odds ratio = 7.20, P = .00) and a negative urine drug screen (odds ratio = .56, P = .04) were significant predictors of being in HBP care. Low alcoholism risk and employment were identified as significant predictors of compliance with HBP medication-taking behavior. Men currently using illicit drugs were 2.64 times less likely to have controlled BP compared with their counterparts who did not use illicit drugs, and men currently taking HBP medication were 63 times more likely have controlled BP compared with men not taking HBP medication. Comprehensive interventions are needed to address socioeconomic and lifestyle issues as well as other barriers to care and treatment, if HBP care is to be salient and effective in this high risk group.
Assuntos
População Negra , Hipertensão/terapia , Adulto , Humanos , Hipertensão/etnologia , Hipertensão/etiologia , Seguro Saúde , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Transtornos Relacionados ao Uso de Substâncias/complicaçõesRESUMO
Hypertensive patients with target organ damage are at increased cardiovascular risk, and should be treated most aggressively. The association between urinary albumin excretion and left ventricular hypertrophy (LVH) in prior studies is inconsistent, and has not been described using a single, random spot urine specimen. Therefore, we evaluated the association between the urinary albumin creatinine ratio (ACR) and left ventricular (LV) mass and also tested the hypothesis that a simple random, single-void urine ACR would identify high risk young, hypertensive, African-American men. We measured echocardiographic LV mass and a random spot urinary ACR in 109 untreated, hypertensive, young, inner city, African-American men. The mean age was 41 +/- 6 years and the mean blood pressure (BP) was 157 +/- 19/107 +/- 13 mm Hg. Microalbuminuria (ACR 30 to 300 mg/g) was present in 22% of subjects. The ACR is higher in the men with LVH than in the men without LVH (P < .05). Increased ACR is a predictor of increased LV mass index (P < .003) using multiple linear regression. An ACR >30 mg/g has a sensitivity of 33% and a specificity of 82% for the diagnosis of echocardiographic LVH. In conclusion, elevated random spot ACR is a marker of increased LV mass, independent of BP, in young urban African-American men with hypertension, and may help to determine the aggressiveness of antihypertensive therapy in this high-risk group.
Assuntos
Albuminúria/metabolismo , População Negra , Creatinina/urina , Hipertrofia Ventricular Esquerda/diagnóstico , Adolescente , Adulto , Pressão Sanguínea/fisiologia , Humanos , Hipertensão/etnologia , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/urina , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Saúde da População Urbana , Função Ventricular Esquerda/fisiologiaRESUMO
This randomized trial recruited and followed underserved, inner-city, hypertensive (HTN), young black men and investigated whether a nurse-community health worker team in combination with usual medical care (SI) increased entry into care and reduced high blood pressure (HBP), in comparison to usual medical care (UC) alone. Emergency department records, advertising, and BP screenings identified potential participants with HBP. Telephone calls and personal contacts tracked enrollees. Of 1391 potential participants, 803 (58%) responded to an invitation to be screened and scheduled a visit. Of these, 528 (66%) kept an appointment, 207 (35%) were BP eligible, and 204 (99%) consented to enroll. At 12 months 91% of men were accounted for and 85.8% (adjusted for death, in jail, or moved away) were seen. Mean BP changed from 153(16)/98(10) to 152(19)/94(11) mm Hg in the SI group and 151(18)/98(11) to 147(21)/92(14) mm Hg in the UC group (P = NS). High rates of participation are attainable in this population; however, culturally acceptable ways of delivering HBP care are needed.
Assuntos
Hipertensão/tratamento farmacológico , Adulto , Negro ou Afro-Americano , População Negra , Pressão Sanguínea/efeitos dos fármacos , Seguimentos , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Seleção de Pacientes , Qualidade da Assistência à Saúde , Tamanho da Amostra , Resultado do Tratamento , População UrbanaRESUMO
The results of 12,168 precipitin tests on blood meals of mosquitoes of the Kano Plain caught by a variety of catching techniques indicate that to gain an accurate overall picture of feeding patterns both the indoor and the outdoor biotope must be sampled. CDC light traps operated inside houses and Monkswood type light traps operated under the outside eaves of houses were found to collect larger numbers of blood fed specimens from a wider range of species than battery driven aspirators collecting from natural resting sites. The results indicated that 7 mosquito species entered houses to bite man in appreciable numbers in the Kisumu area. These were Anopheles gambiae s.l., A. funestus, A. pharoensis, Mansonia uniformia, M. africana, Culex antennatus, and C. univittatus. Eight mosquito species were found to bite man and domestic animals in the outdoor biotope in large numbers. These were: A. pharoensis, A. ziemanni, M. uniformis, M. africana, C. antennatus, C. univittatus, Aedes circumluteolus, and Ae. ochraceus. From an epidemiological point of view, species with a narrow range of hosts are most likely to be of importance as vectors of parasitic diseases such as malaria and into this category fall the major man biting anophelines A. gambiae and A. funestus. Those mosquito species which switch from one group of hosts to another according to local circumstances are most likely to be involved in arbovirus transmission and in this group the following species must be considered: A. pharoensis, A. ziemanni, M. uniformia, M. africana, C. antennatus, C. univittatus and Ae. circumluteolus.
Assuntos
Vetores Artrópodes , Culicidae , Animais , Infecções por Arbovirus/transmissão , Sangue , Cruzamento , Ritmo Circadiano , Ecologia , Comportamento Alimentar , Habitação , Humanos , Quênia , Estilo de Vida , Especificidade da Espécie , Abastecimento de ÁguaRESUMO
14 strains of Getah virus were isolated from a variety of mosquito species collected in Sarawak between October 1968 and February 1970. Ten strains were isolated from C. tritaeniorhynchus 7 of them at K. Tijirak. Single strains were isolated from C. gelidus, C. pseudovishnui, M. bonneae/dives and Aanopheles species. 6 of the isolates were obtained in October 1968 when Japanese encephalitis, Tembusu and Sindbis viruses were also very active. The available evidence suggest that Getah virus in Sarawak is maintained in a cycle similar to that of Japanese encephalitis virus and involves C. tritaeniorhynchus, C. gelidus and domestic pigs.
Assuntos
Infecções por Arbovirus/história , Arbovírus/isolamento & purificação , Vetores Artrópodes , Culicidae , História do Século XX , Humanos , Malásia , Vírus da Floresta de Semliki/classificação , Vírus da Floresta de Semliki/isolamento & purificaçãoRESUMO
The possible role of pigs as arbovirus maintenance hosts and their importance as amplifier hosts was studied. Blood samples from 464 pigs of all ages collected in 1962 and 1964 were tested against 10 arboviruses. Antibodies to Japanese encephalitis and Getah viruses were particularly prevalent and their calculated monthly infection rates were 19-5% and 13-3% respectively. In 1969, 447 pigs were bled monthly throughout the year and the infection rates for Japanese encephalitis virus were calculated in pigs during the first year of life. Infection rates were not uniform throughout the year; the rate increases as the pig grew older and there was a marked seasonal increase in the infection rate in the period from November to January. This coincided with the seasonal major population peak of Culex tritaeniorhynchus following intense breeding of this mosquito prior to rice planting. It is suggested that, in Sarawak, the pig acts as a maintenance host of Japanese encephalitis in a cycle involving C. gelidus mosquitoes and also acts as an important amplifier host towards the end of the year in a cycle involving C. tritaeniorhynchus. It is further suggested that Getah virus is maintained in a similar cycle between C. tritaeniorhynchus and pigs.
Assuntos
Infecções por Arbovirus/diagnóstico , Reservatórios de Doenças , Suínos/microbiologia , Fatores Etários , Animais , Culex/microbiologia , Vírus da Encefalite Japonesa (Espécie)/imunologia , Testes de Inibição da Hemaglutinação , Humanos , Malásia , Testes de Neutralização , Estações do AnoRESUMO
Arbovirus isolation attempts on 324,486 mosquitoes captured over a four-year period on the Kano Plain, Kenya, yielded 15 isolates including Pongola (six strains), Ilesha (three strains), Germiston (two strains), Sindbis (one strain), Barur (one strain) and two viruses which could not be characterized. Mansonia uniformis, Anopheles gambiae and Culex antennatus constituted 70% of the total collection and accounted for all of the isolates except one, which came from Anopheles funestus.
Assuntos
Arbovírus/isolamento & purificação , Culicidae/microbiologia , Animais , QuêniaRESUMO
PURPOSE: This study was conducted to determine diabetes care priorities and needs in a group of urban African American adults with type 2 diabetes mellitus. METHODS: One hundred nineteen African American adults with type 2 diabetes, aged 35 to 75, received behavioral/educational interventions from a nurse case manager, a community health worker, or both. Priorities and needs were assessed during 3 intervention visits. RESULTS: The most frequently reported priorities for diabetes care were glucose self-monitoring (61%), medication adherence (47%), and healthy eating (36%). The most frequently addressed diabetes needs were glucose self-monitoring and medication adherence. Most of the intervention visits (77%) addressed non-diabetes-related health issues such as cardiovascular disease (36%) and social issues such as family responsibilities (30%). CONCLUSIONS: Participants' self-reported priorities for diabetes care directly reflected the diabetes needs addressed. Needs beyond the focus of traditional diabetes care (social issues and insurance) are important to address in urban African Americans with type 2 diabetes. Interventions designed to address comprehensive health and social needs should be included in treatment and educational plans for this population.
Assuntos
Negro ou Afro-Americano , Diabetes Mellitus Tipo 2/psicologia , Satisfação do Paciente , Adulto , Automonitorização da Glicemia , Diabetes Mellitus Tipo 2/reabilitação , Escolaridade , Humanos , Educação de Pacientes como Assunto , Estados Unidos , População UrbanaRESUMO
Community-based nurses and health workers who supplement physician office-based practice are known to be effective in promoting cardiovascular health. They enhance the effectiveness of programs to influence individual and population lifestyles, self-care practices, and long-term adherence to recommendations. As a team they are able to focus on economic, psychosocial, and behavioral factors in culturally relevant ways, often missed in traditional medical care, by attending comprehensively to education, income, employment status, living arrangements, and daily needs. Much can be learned about these teams from the past by reviewing the roles, supporting data, and practice-related issues. There are two important points to be made about the nurse and the community health worker in cardiovascular health promotion: (1) these roles are not new; and (2) reported control rates for high blood pressure and other risk factors are highest when multidisciplinary teams help patients actively participate in the treatment/prevention program. Promoting cardiovascular health across all segments of society with greater emphasis on prevention will require that the barriers to interdisciplinary collaboration and full community partnership be reduced or eliminated.