RESUMO
There is growing support to reverse mass incarceration in the United States, especially in the wake of the COVID-19 pandemic. Little is known about what types and scale of community investments are most effective to support mass decarceration. Using a public health prevention framework, we conducted a scoping review to examine community-based programs that reduced criminal legal involvement. We searched PubMed, Embase and three EBSCO databases from 1990 through September 2019 for all experimental or quasi-experimental studies testing interventions pertaining to education, housing, healthcare, employment, or social support services and how they affected an individual's criminal legal outcomes. Our review identified 53 studies that demonstrated the efficacy of early childhood educational interventions and nurse-family partnership programs, post-secondary education for incarcerated students, navigation programs linking incarcerated people to community resources, and peer support upon release to reduce criminal legal system exposure. In concert with legislative action to end mass incarceration, additional research is needed to test interventions designed to achieve mass decarceration which cross multiple domains, interrogate community-level impacts and ascertain long-term outcomes.
RESUMO
The aim of this paper was to describe and test a social cognitive model of physical activity tailored for adolescent girls. Participants were 1518 girls (aged 13.6 ± 0.02 years) from 24 secondary schools in New South Wales, Australia. Useable accelerometer (≥10 hours day(-1) on at least 3 days) and questionnaire data were obtained from 68% of this sample (N = 1035). Participants completed questionnaires assessing psychological, behavioural, social and environmental correlates of activity. The theoretical model was tested using structural equation modelling in AMOS. The model explaining accelerometer counts per minute was an adequate-to-good fit to the data (Tucker-Lewis Index = 0.89, the comparative fit index = 0.97 and the root mean square of approximation = 0.098; 90% confidence interval = 0.075-0.122) but explained only 5% of the variance in activity. There were significant model pathways from self-efficacy (r = 0.11, P = 0.01), school environment (r = 0.07, P = 0.02) and physical self-worth (r = 0.07, P = 0.04) to accelerometer counts. Although the proposed model provided an adequate-to-good fit to the data, it explained a small portion of the variance. Shared method variance may explain the larger portions of variance explained in previous studies. Future studies are encouraged to evaluate theories of physical activity behaviour change using objective measures of physical activity.
Assuntos
Modelos Psicológicos , Atividade Motora , Psicologia do Adolescente , Actigrafia , Adolescente , Feminino , Humanos , New South Wales , Educação Física e Treinamento/métodos , Inquéritos e QuestionáriosRESUMO
The well-known side effects of anticholinergic compounds used to treat urinary incontinence caused by detrusor overactivity have addressed the interest on other pharmacological intervention. The purpose of the present work was to investigate the possible changes in purinergic and cholinergic components of parasympathetic neurotransmission in obstructed rat bladders with detrusor overactivity, and to examine the effect of the association of suramin, atropine and indomethacin on nerve-mediated responses to electrical field stimulation (EFS). Mechanical responses to exogenous acetylcholine, ATP and substance P were also evaluated. Altered sensitivities to acetylcholine and to the sensory neurotransmitter substance P, but unchanged sensitivity to the stable ATP analogue alpha,beta-methyleneATP were observed in bladders from obstructed rats. Suramin and atropine inhibited purinergic and cholinergic components of the neurogenic responses evoked by EFS in detrusor strips from control and obstructed rats. Interestingly, suramin enhanced the antagonistic effect of atropine on neurogenic responses of detrusor strips at all frequencies of stimulation tested. Our results suggest that the association between an antimuscarinic drug and an antagonist of P2X purinoceptors such as suramin might be helpful to reduce the therapeutic dosage of the antimuscarinic drug, along with its side effects. This approach may be of interest in the therapy of patients with bladder incontinence caused by detrusor overactivity, which do not even respond to a maximal dosage of antimuscarinic drug.
Assuntos
Acetilcolina/farmacologia , Trifosfato de Adenosina/farmacologia , Músculo Liso/efeitos dos fármacos , Substância P/farmacologia , Obstrução do Colo da Bexiga Urinária/fisiopatologia , Trifosfato de Adenosina/análogos & derivados , Animais , Atropina/farmacologia , Agonistas Colinérgicos/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Estimulação Elétrica , Feminino , Técnicas In Vitro , Indometacina/farmacologia , Ácidos Mandélicos/farmacologia , Agonistas Muscarínicos/farmacologia , Contração Muscular/efeitos dos fármacos , Músculo Liso/inervação , Ratos , Ratos Sprague-Dawley , Suramina/farmacologia , Uretra/fisiopatologia , Bexiga Urinária/inervaçãoRESUMO
A symptomatic case of diaphragmatic hernia through the foramen of Morgagni-Larrey in an adult patient is presented. Etiology, diagnosis and particularly, indications of differences between open and laparoscopic repair of diaphragmatic hernia are discussed. In the case presented laparoscopic technique was carried out by means of tension-free closure of the defect using extraperitoneal prolene-mesh. The recovery was quick and uneventful. Four years after surgery no compliants were noticed.
Assuntos
Hérnia Diafragmática/cirurgia , Laparoscopia , Implantação de Prótese , Telas Cirúrgicas , Cirurgia Vídeoassistida , Adulto , Humanos , Masculino , Estresse MecânicoRESUMO
Diabetes is associated with gender-specific macrovascular complications arising from increased oxidant stress in the vascular wall. In this study, male and female rats were treated with two structurally unrelated drugs sharing antioxidant properties, lercanidipine and Leucoselect (both 3 mg/kg/day), for 1 week starting 1 day after streptozotocin-diabetes induction. Concentration-response curves to L-nitroarginine methylester (L-NAME), superoxide dismutase and acetylcholine in aortic rings showed significantly greater nitric oxide-mediated relaxation in female compared with male non-diabetic rats. Diabetes increased contractility to noradrenaline and L-NAME in both genders, whereas relaxation to acetylcholine and iloprost were significantly attenuated in females only. Treatment with lercanidipine and Leucoselect restored, at least in part, responses to noradrenaline, acetylcholine and iloprost without affecting those to L-NAME and sodium nitroprusside. Unexpectedly, both drugs impaired superoxide dismutase response in female tissues. In conclusion, female rat aorta is markedly exposed to short-term diabetic vascular injury, which may be prevented by antioxidant treatment.
Assuntos
Antioxidantes/farmacologia , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus/fisiopatologia , Di-Hidropiridinas/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Fatores Sexuais , Acetilcolina/farmacologia , Animais , Aorta Torácica/efeitos dos fármacos , Glicemia/análise , Diabetes Mellitus/sangue , Feminino , Iloprosta/farmacologia , Técnicas In Vitro , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Doadores de Óxido Nítrico/metabolismo , Nitroprussiato/farmacologia , Norepinefrina/farmacologia , Ratos , Superóxido Dismutase/farmacologia , Vasoconstrição , Vasodilatadores/farmacologiaRESUMO
The understanding of the biological effects of estrogen on the vessel wall has improved dramatically since the discovery of estrogen receptors (ERs). Most, but not all estrogen-mediated effects in blood vessels are thought to be mediated by ERs. Two major ER subclasses have been characterized so far: the ERalpha and the more recently described ERbeta. This review will primarily focus on a new perspective that highlights ERs as essential mediators of the vascular effects of estrogen. In view of the rising research interest in this area, it can be also expected that tissue- and ER subclass-selective agonists and antagonists will be developed over the next few years, thus providing invaluable tools for pharmacological and clinical applications.
Assuntos
Vasos Sanguíneos/metabolismo , Estrogênios/metabolismo , Receptores de Estrogênio/metabolismo , Animais , Vasos Sanguíneos/anatomia & histologia , Doenças Cardiovasculares/metabolismo , Estrogênios/agonistas , Estrogênios/química , Feminino , Humanos , Masculino , Estrutura Molecular , Receptores de Estrogênio/genética , Moduladores Seletivos de Receptor Estrogênico/metabolismoRESUMO
Diabetes mellitus reduces gender-related differences in the prevalence of cardiovascular disease by fading the vascular protective effects afforded by estrogen in females. However, the impact of estrogen treatment on and the contribution of androgens to vascular function in vessels from male diabetics are largely unknown. We investigated the effects of androgen deficiency and in vivo estrogen treatment by assessing the responsiveness to a number of vasoactive agents and the formation of eicosanoid mediators in aortic rings from intact and castrated streptozotocin-diabetic rats which had been implanted with 17beta-estradiol (E2) or its vehicle for 5 days. Castration was found to attenuate contractility to noradrenaline, to enhance tone-related release of NO, as shown by curves for N-methyl-L-arginine and superoxide dismutase (SOD), and to increase endothelium-dependent relaxation to carbachol and histamine, compared with intact animals. Smooth muscle sensitivity to exogenous NO and platelet thromboxane A2 production were unchanged but prostacyclin release by aortic tissue dropped by about 40% following castration. Treatment with E2 to intact animals still attenuated contractility to noradrenaline and potentiated relaxation to SOD and histamine but affected no other parameters. In contrast, when E2 was administered to castrated animals, responses to SOD, carbachol and histamine were significantly impaired. Thus, androgen deprivation appears to improve vascular function in male diabetic rats, whereas E2 treatment exerts some beneficial effects in intact, but not in castrated animals. Our findings therefore provide new insights into the role of sex hormones in the development of diabetic vascular complications.
Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Estrogênios/farmacologia , Vasoconstrição/efeitos dos fármacos , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Aorta/fisiologia , Plaquetas/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Interações Medicamentosas , Eicosanoides/biossíntese , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Técnicas In Vitro , Masculino , Óxido Nítrico/metabolismo , Doadores de Óxido Nítrico/farmacologia , Norepinefrina/farmacologia , Ratos , Ratos Sprague-Dawley , Estreptozocina , Vasoconstritores/farmacologia , ômega-N-Metilarginina/farmacologiaRESUMO
Estrogen deficiency is one of the factors involved in the stress incontinence in postmenopausal women, and estrogens have been used clinically in the treatment of urinary disorders during menopause. Sex hormones seem to be also involved in the diabetic changes of urinary bladder and urethra, because ovariectomy causes an increase in the micturition of streptozotocin-diabetic rats. In the present study diabetic and healthy female rats were used to investigate the effect of 17beta-estradiol on mechanical contractions to norepinephrine and to KCI and relaxations to ATP on isolated proximal urethral preparations as well as on contractions to ACh, ATP and KCl on detrusor smooth muscle strips. The data were compared with those obtained in OVX animals, with or without estradiol replacement. The present study showed that ovariectomy decreased the responses to ATP, NE and KCl in urethral preparations, and responses to ATP, ACh and KCl in bladder strips from both healthy and diabetic rats. Diabetes appeared to potentiate the effect of ovariectomy in both tissues. Estrogen replacement was able to recover functional responses in urethras of healthy rats. In diabetic rats, this treatment partially restored ATP-induced responses in both tissues, almost completely restored those to NE in urethra and those to ACh in bladder. This study clearly indicated that abnormalities of urethra and bladder function caused by ovariectomy can be restored by estrogen treatment also in diabetic animals, at least at an early stage of disease.
Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Estradiol/farmacologia , Uretra/efeitos dos fármacos , Bexiga Urinária/efeitos dos fármacos , Trifosfato de Adenosina/farmacologia , Animais , Relação Dose-Resposta a Droga , Feminino , Técnicas In Vitro , Contração Muscular/efeitos dos fármacos , Norepinefrina/farmacologia , Ovariectomia , Cloreto de Potássio/farmacologia , Ratos , Ratos Sprague-Dawley , Uretra/fisiologia , Bexiga Urinária/fisiologiaRESUMO
The beneficial effects of estrogen on arterial function in women are well established, whereas studies concerning the vascular role of androgens have produced conflicting results. In the present study, we examined the effects of androgen deprivation and of estrogen treatment on vascular responses in male rats. Vascular reactivity was studied in aortic rings excised from intact and castrated rats, which had been implanted with capsules containing either 17beta-estradiol (E2) or its vehicle for 5 days. Contractile responses to noradrenaline were potentiated by castration and by E2 treatment. Concentration-response curves for N-methyl-L-arginine and superoxide dismutase indicated that the tone-related release of NO increased in tissues from castrated, compared with intact rats, but was not affected by E2 treatment. Endothelium-dependent relaxation elicited by carbachol and histamine were not altered by castration and were attenuated by E2 in preparations from intact, but not from castrated rats. Moreover, aortic prostacyclin release dropped by about 40% after E2 treatment in tissues from both intact and castrated animals. Similarly, smooth muscle sensitivity to NO significantly decreased following castration and E2 treatment, as assessed by responses to sodium nitroprusside. Finally, no differences among groups were detected in platelet thromboxane A2 production. Thus, vascular responses in male rats were not improved by androgen deprivation alone or by E2 treatment, whose effects differed in the presence or absence of androgens. These findings provide evidence for the gender specificity of the vascular effects of estrogen and may be consistent with a beneficial role of physiologic levels of male sex hormones in arterial function.
Assuntos
Androgênios/fisiologia , Aorta/efeitos dos fármacos , Estradiol/farmacologia , Animais , Aorta/fisiologia , Eicosanoides/biossíntese , Técnicas In Vitro , Masculino , Óxido Nítrico/biossíntese , Norepinefrina/farmacologia , Orquiectomia , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/farmacologia , Vasoconstrição/efeitos dos fármacos , ômega-N-Metilarginina/farmacologiaRESUMO
Isolated epithelial layer preparations were obtained from urinary bladders of 4-week streptozotocin-diabetic rats and used for endogenous prostaglandins E(2) and F(2alpha) determination. Tissues were incubated in modified Krebs solution under basal conditions, or in the presence of either indomethacin (5x10(-7) M), ATP (10(-5) and 10(-3) M) or bradykinin (10(-7) and 10(-5) M), and samples of incubation medium were collected at 15 and 30 min. In the presence of indomethacin, the release of prostaglandins in the incubation medium was under the detection limit of the enzyme immunoassay (EIA). The epithelium from diabetic rat urinary bladders was thicker and heavier and the absolute amount of endogenous prostaglandins E(2) and F(2alpha) was higher than for control animals, but when prostaglandin production was expressed as a fraction of tissue weight, it was reduced in diabetic epithelium. ATP and bradykinin has significantly increased the endogenous release of both prostaglandins from the epithelium when compared with the release under basal conditions. This increase was time-dependent and was higher in diabetic than in control tissues. ATP evoked a phasic and tonic contraction in bladder strips that was abolished by epithelium removal. Concentration-response curves for ATP did not differ among groups. Bradykinin evoked a long-lasting tonic contraction that was reduced significantly by epithelium removal in diabetic rat bladders only. Concentration-response curves for prostaglandin E(2) and F(2alpha) in diabetic rat bladder differed significantly from that in controls and epithelium removal did not alter these responses. It is suggested that bradykinin receptors and P2X nucleotide receptors already found in the smooth muscle detrusor might be present in the epithelial layer of the bladder. The prostaglandin-release impairment observed in this study might be responsible, in part, for bladder abnormalities observed in pathological conditions, such as diabetes.
Assuntos
Diabetes Mellitus Experimental/metabolismo , Dinoprosta/metabolismo , Dinoprostona/metabolismo , Bexiga Urinária/metabolismo , Urotélio/metabolismo , Trifosfato de Adenosina/farmacologia , Animais , Bradicinina/farmacologia , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/fisiopatologia , Ensaio de Imunoadsorção Enzimática , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/patologia , Bexiga Urinária/fisiopatologia , Urotélio/efeitos dos fármacos , Urotélio/patologia , Urotélio/fisiopatologiaRESUMO
We describe a site http://users.unimi.it/-ratserum/homeframed.ht ml with clickable maps of serum proteins of control and inflamed rats as well as quantitative data on the expression of such serum proteins under varying physiological and experimental conditions. This information enhances the value of minimally invasive techniques, thus reducing the number of animals to be treated, and eventually sacrificed, in pharmacological/toxicological research projects.
Assuntos
Proteínas Sanguíneas , Internet , Animais , Eletroforese em Gel Bidimensional , RatosRESUMO
Changes in the concentration of major serum proteins were monitored from day 0 to day 4 in three experimental groups: rats injected with turpentine, rats receiving the turpentine shot and daily doses of indomethacine, and rats given indomethacine alone. In inflamed animals, peak changes for acute-phase reactants, evaluated by two-dimensional electrophoresis (2-DE), were usually observed between 48 and 72 h after the phlogistic stimulus. By itself, indomethacine was found to affect the synthesis of most proteins (except one of the thiostatin variants and ceruloplasmin); the changes in serum levels, whether positive or negative, were the same as upon inflammation (except for kallikrein-binding protein), but their extent and/or timing usually differed. When inflamed animals were given indomethacine, a clear-cut difference in the concentration of some proteins was observed versus inflamed rats not given medication, at 24 h after the start of the treatments. Proteins mainly affected were alpha2-macroglobulin, alpha2-HS-glycoprotein, C-reactive protein and kallikrein-binding protein.
Assuntos
Proteínas de Fase Aguda/metabolismo , Anti-Inflamatórios não Esteroides/farmacologia , Indometacina/farmacologia , Animais , Eletroforese em Gel Bidimensional , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
We describe how marking nitrocellulose membranes with horseradish peroxidase can be a useful and cheap method to obtain specific badges on zymograms, developed via enhanced chemiluminescence (ECL).
Assuntos
Colódio , Peroxidase do Rábano Silvestre , Membranas Artificiais , BiomarcadoresRESUMO
Several studies have provided evidence for a direct effect of 17beta-estradiol on vessel wall via interaction with the constitutively expressed nitric oxide synthase (NOS) by endothelium. The aim of the present study was to investigate the effect of 17beta-estradiol on inducible NOS (NOS II) in primary culture of smooth muscle cells (SMC) from rat aorta. We here prove that 17beta-estradiol decreases the content and activity of NOS II in SMC. This effect appears to be the consequence of ER activation, because: 1) ER alpha and ER beta are expressed in rat aorta SMC grown in culture; 2) low concentrations of hormone modulate NOS II activity; 3) the specific ER alpha antagonist ICI182,780 completely blocks 17beta-estradiol effect. On the other hand, progesterone is deprived of any effect on NOS II content or activity, proving the specificity of 17beta-estradiol effect. In addition, we show that 17beta-estradiol can counteract the increase in NOS II activity following cytokine treatment. The observation could indicate a novel mechanism for the protective effects exerted by these hormones in cardiovascular diseases and atherosclerosis in particular.
Assuntos
Estradiol/farmacologia , Músculo Liso Vascular/enzimologia , Óxido Nítrico Sintase/biossíntese , Animais , Aorta , Células Cultivadas , Estradiol/administração & dosagem , Estradiol/análogos & derivados , Antagonistas de Estrogênios/farmacologia , Fulvestranto , Masculino , Óxido Nítrico Sintase Tipo II , Nitritos/metabolismo , Progesterona/farmacologia , RNA Mensageiro/análise , Ratos , Ratos Sprague-Dawley , Receptores de Estrogênio/antagonistas & inibidores , Receptores de Estrogênio/genética , Receptores de Estrogênio/fisiologia , Tamoxifeno/farmacologiaRESUMO
Estrogen is known to exert a protective effect against cardiovascular disease. However, women with diabetes have three times the risk as compared with age-matched non-diabetic women. Our previous study on aortic rings of ovariectomized (OVX) female rats treated with 17-beta-estradiol (E2) demonstrated that the beneficial effect of estrogen is related to the basal release of NO from endothelial cells. In the present study, in order to understand why estrogen protection is abolished in diabetes, we tested vascular responses in OVX, streptozotocin-diabetic female rats and their non-diabetic controls receiving or not E2 replacement. Concentration-response curves to norepinephrine (NE) showed attenuation of the contractile response in E2-treated diabetic, with respect to non-diabetic preparations. This response was further impaired in diabetic, E2-deprived rats. The basal release of NO, as evaluated by concentration-related responses to N(G)-methyl-L-arginine acetate in NE-precontracted aortic rings, was found to be impaired in E2-treated diabetic rats, no further effect being induced by E2 deprivation. The endothelium-dependent relaxation produced by carbachol did not change between groups, whereas the relaxation produced by histamine was enhanced by both diabetes and E2 deprivation. However, E2 treatment counteracted the response to histamine only in preparations from non-diabetic animals. Finally, the relaxation induced by sodium nitroprusside, an endothelium-independent relaxant agent, was comparable between groups. These findings suggest that the lack of protective effects of estrogen in diabetes may be mainly ascribed to the failure of estrogen to reverse the impaired basal release of NO and the abnormal relaxation to histamine, which are observed in the aorta of diabetic rats.
Assuntos
Diabetes Mellitus Experimental/metabolismo , Estradiol/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Animais , Aorta/efeitos dos fármacos , Aorta/fisiologia , Carbacol/farmacologia , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Feminino , Histamina/farmacologia , Técnicas In Vitro , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Músculo Liso Vascular/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Nitroprussiato/farmacologia , Ovariectomia , Ratos , Ratos Sprague-Dawley , Estreptozocina , Superóxido Dismutase/farmacologiaRESUMO
Electrical field stimulation caused frequency-dependent relaxations in precontracted strips of hamster proximal urethra, which were attenuated by L-N(G)-nitroarginine methyl ester (10(-4) M) and completely blocked by tetrodotoxin (10(-6) M). Strips of hamster urethra devoid of urothelium showed reduced relaxant responses to electrical field stimulation which were abolished by L-N(G)-nitroarginine methyl ester (10(-4) M). Western blot analysis showed the presence of a constitutive endothelial nitric oxide synthase in the urothelial layer, suggesting that urothelium may release nitric oxide in response to electrical field stimulation and that this release is blocked by tetrodotoxin. It is suggested that the urothelium may contribute to relaxations of the smooth muscle of hamster urethra produced by nerve stimulation.
Assuntos
Óxido Nítrico Sintase/análise , Uretra/enzimologia , Urotélio/enzimologia , Animais , Arginina/análogos & derivados , Arginina/farmacologia , Western Blotting , Cricetinae , Estimulação Elétrica , Inibidores Enzimáticos/farmacologia , Técnicas In Vitro , Masculino , Mesocricetus , Contração Muscular/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiologia , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase Tipo III , Tetrodotoxina/farmacologia , Uretra/efeitos dos fármacos , Uretra/fisiologia , Urotélio/citologiaRESUMO
1. Nitric oxide (NO) is known from previous studies to be the principle transmitter in NANC inhibitory nerves supplying the hamster urethra. However, the identity of the cotransmitter(s) responsible for the responses remaining following block with L-NG-nitroarginine methyl ester (L-NAME) is not known. 2. Electrical field stimulation (EFS) of circular strips of hamster proximal urethra precontracted with arginine vasopressin (AVP 10(-8) M), and in the presence of phentolamine (10(-6) M), propranolol (10(-6) M) and atropine (10(-6) M), caused frequency-dependent relaxation, which was attenuated by suramin (10(-4) M) and reactive blue 2 (RB2; 2 x 10(-4) M), but not by pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 10(-4) M), alpha-chymotrypsin (10-50 u ml(-1)) or by the vasoactive intestinal polypeptide (VIP) antagonist, [Lys1, Pro2,5, Arg3,4, Tyr6]-VIP, (5 x 10(-7)-10(-6) M). In the presence of indomethacin (10(-6) M) frequency-dependent relaxations to EFS were enhanced, particularly at the lower frequencies of stimulation. EFS-induced relaxation was blocked by tetrodotoxin (10(-6) M), indicating its neurogenic origin. 3. Exogenous ATP (10(-7)-10(-3) M) produced concentration-related relaxations which were attenuated by the P2-purinoceptor antagonists suramin (10(-4) M) and RB2 (2 x 10(-4) M) but not by PPADS (10(-4) M). ATP-induced relaxations were also reduced significantly by indomethacin (10(-6) M). The inhibitory responses to ATP were urothelium- and NO-independent, since they were not affected by either removal of urothelium or by L-NAME (10(-4) M). 4. Exogenous VIP (10(-9)-10(-7) M) induced concentration-related relaxations which were not affected by urothelium removal, L-NAME (10(-4) M), alpha-chymotrypsin (10-50 u ml(-1)) or by [Lys1, Pro2,5, Arg3,4, Tyr6]-VIP (3 x 10(-7)-10(-6) M). Nevertheless, suramin (10(-4) M) and RB2 (2 x 10(-4) M) but not PPADS (10(-4) M) antagonized the VIP-induced relaxant responses. Calcitonin gene-related peptide (CGRP: 10(-9)-10(-7) M) was devoid of any effect or only elicited a small relaxant response in AVP-precontracted strips. 5. Exogenous prostaglandin E2 (PGE2; 10(-9)-3 x 10(-6) M) and the NO donor, sodium nitroprusside (SNP; 10(-8)-3 x 10(-5) M) elicited concentration-related relaxations on the hamster proximal urethra which were not attenuated by suramin (10(-4) M), RB2 (2 x 10(-4) M), or by PPADS (10(-4) M), indicating a specific inhibitory effect of the antagonists used. 6. In summary, these results are consistent with the view that ATP is an inhibitory transmitter released from inhibitory nerves supplying the NANC relaxation of hamster proximal urethra. The relaxant effect of ATP is NO- and urothelium-independent. The present study did not demonstrate whether VIP is released from parasympathetic nerves during EFS, since both alpha-chymotrypsin and [Lys1, Pro2,5, Arg3,4, Tyr6]-VIP were ineffective on neurogenic responses.
Assuntos
Trifosfato de Adenosina/farmacologia , Uretra/efeitos dos fármacos , Peptídeo Intestinal Vasoativo/farmacologia , Animais , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Cricetinae , Dinoprostona/farmacologia , Masculino , Mesocricetus , Relaxamento Muscular/efeitos dos fármacos , Óxido Nítrico/farmacologia , Nitroprussiato/farmacologia , Fosfato de Piridoxal/análogos & derivados , Fosfato de Piridoxal/farmacologia , Suramina/farmacologia , Triazinas/farmacologia , Uretra/inervação , Uretra/fisiologiaRESUMO
This investigation sought to determine how different components of the hemostatic system affect the development of venous thrombosis in rats displaying hyperlipidemia, either on a genetic basis or secondary to metabolic disorders. On employing an experimental model of collagen-triggered venous thrombosis, both spontaneously hyperlipidemic (Yoshida strain) and streptozotocin-induced diabetic rats generated about 2.3-fold greater thrombi than normolipidemic controls. This was associated with significant platelet activation, as revealed by increased levels of serum thromboxane B2 in diabetics (1.5-fold) as well as in Yoshida (8-fold) rats, in comparison with controls. In contrast, ex vivo total fibrinolytic activity, as measured by euglobulin lysis time, did not differ between normo- and hyperlipidemic or diabetic animals. Plasminogen activator inhibitor activity was lower in both Yoshida and diabetic rats than in controls. However, tissue-type plasminogen activator activity was differently affected by the genetic or the diabetes-related hyperlipidemia, showing significantly lower values in Yoshida (-26%), but significantly higher values in diabetic rats (+29%) than in normolipidemic controls. We conclude that platelet activation, rather than consistent modifications of the fibrinolytic system, is likely to influence the enhanced thrombus development associated with primary or secondary forms of hyperlipidemia.
Assuntos
Hiperlipidemias/sangue , Ativação Plaquetária , Tromboflebite/sangue , Tromboflebite/etiologia , Animais , Modelos Animais de Doenças , Fibrinólise , Masculino , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos , Ratos Sprague-Dawley , Tromboxano B2/sangueRESUMO
1. Purinergic and cholinergic components of parasympathetic neurotransmission and contractile responses to exogenous alpha,beta-methylene ATP, acetylcholine, substance K, substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide and capsaicin have been investigated in the urinary bladder of hibernating hamsters (4 weeks), cold exposed (4 weeks) and age-matched controls. 2. Electrical field stimulation (EFS) evoked increased frequency-dependent contractions in the detrusor strips from hibernating hamsters compared with those obtained from cold-exposed and age-matched animals. Tetrodotoxin (10(-6) M) completely blocked the frequency-dependent contractions in all groups. 3. The purinergic component of the parasympathetic neurotransmission was not affected in hibernating and cold-exposed animals while the cholinergic component was increased with respect to age-matched animals. The neurogenic response to EFS, still present after incubation with atropine (10(-6) M) and suramin (10(-4) M), was attenuated by indomethacin (10(-6) M) and blocked by tetrodotoxin (10(-6) M). 4. Exogenous administration of alpha,beta-methylene ATP elicited a significantly reduced contraction in strips from hibernating and cold-exposed hamsters relative to age-matched animals. The contractile response to exogenous acetylcholine was greater in the detrusors from hibernating hamsters than in cold-exposed and age-matched animals. Substance K elicited reduced contractions in preparations from hibernating animals compared with cold-exposed and control animals. Calcitonin gene-related peptide, vasoactive intestinal polypeptide, substance P and capsaicin did not elicit any relaxant or contractile response either at resting tone or in carbachol (5 x 10(-7) M)-precontracted tissues. 5. In summary, our findings indicate that 4 weeks of hibernation can significantly increase neurogenic responses in the hamster urinary bladder. This appears to be due to an increase in postjunctional responses to acetylcholine. In contrast, there was a decrease of the postjunctional responses to the parasympathetic cotransmitter ATP and also to the sensory-motor neurotransmitter substance K.
Assuntos
Hibernação , Bexiga Urinária/fisiologia , Acetilcolina/farmacologia , Trifosfato de Adenosina/análogos & derivados , Trifosfato de Adenosina/farmacologia , Animais , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Cricetinae , Estimulação Elétrica , Masculino , Mesocricetus , Neurocinina A/farmacologia , Substância P/farmacologia , Transmissão Sináptica/efeitos dos fármacos , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/inervação , Peptídeo Intestinal Vasoativo/farmacologiaRESUMO
1. A brief challenge of rat astrocytes with either alpha, beta-methyleneATP (alpha, beta-meATP) or basic fibroblast growth factor (bFGF) resulted, three days later, in morphological differentiation of cells, as shown by marked elongation of astrocytic processes. The P2 receptor antagonist suramin prevented alpha, beta-meATP- but not bFGF-induced astrocytic elongation. Similar effects on astrocytic elongation were also observed with ATP and other P2 receptor agonists (beta, gamma meATP, ADP beta S, 2meSATP and, to a lesser extent, UTP). 2. Pertussis toxin completely abolished alpha, beta-meATP- but not bFGF-induced effects. No effects were exerted by alpha, beta-meATP on cyclic AMP production; similarly, neomycin had no effects on elogation of processes induced by the purine analogue, suggesting that adenylyl cyclase and phospholipase C are probably not involved in alpha, beta-meATP-induced effects (see also the accompanying paper by Centemeri et al., 1997). The tyrosine-kinase inhibitor genistein greatly reduced bFGF- but not alpha, beta-meATP-induced astrocytic elongation. 3. Challenge of cultures with alpha, beta-meATP rapidly and concentration-dependently increased [3H]-arachidonic acid (AA) release from cells, suggesting that activation of phospholipase A2 (PLA2) may be involved in the long-term functional effects evoked by purine analogues. Consistently, exogenously added AA markedly elongated astrocytic processes. Moreover, various PLA2 inhibitors (e.g. mepacrine and dexamethasone) prevented both the early alpha, beta-meATP-induced [3H]-AA release and/or the associated long-term morphological changes, without affecting the astrocytic elongation induced by bFGF. Finally, the protein kinase C (PKC) inhibitor H7 fully abolished alpha, beta-meATP- but not bFGF-induced effects. 4. Both alpha, beta-meATP and bFGF rapidly and transiently induced the nuclear accumulation of Fos and Jun. Both c-fos and c-jun induction by the purine analogue could be fully prevented by pretreatment with suramin. In contrast, the effects of bFGF were unaffected by this P2 receptor antagonist. 5. It was concluded that alpha, beta-meATP- and bFGF-morphological differentiation of astrocytes occurs via independent transductional pathways. For the purine analogue, signalling involves a Gi/G(o) protein-coupled P2Y-receptor which may be linked to activation of PLA2 (involvement of an arachidonate-sensitive PKC is speculated); for bFGF, a tyrosine kinase receptor is involved. Both pathways merge on some common intracellular target, as suggested by induction of primary response genes, which in turn may regulate late response genes mediating long-term phenotypic changes of astroglial cells. 6. These findings implicate P2 receptors as novel targets for the pharmacological regulation of reactive astrogliosis, which has intriguing implications in nervous system diseases characterized by degenerative events.