RESUMO
The synthesis of 2(R),3-dihydroxypropyl and 2(R),3(R)-dihydroxybutyl beta-d-fructopyranosides, and some derivatives, employing Sharpless-type catalytic asymmetric dihydroxylation procedures is described. Some aspects of the reactions, including stereoselectivities and chemical evidence for the assigned stereochemistry of the main products are reported.
Assuntos
Aminoglicosídeos/síntese química , Aminoglicosídeos/química , Catálise , Hidroxilação , Conformação Molecular , Estrutura Molecular , Estereoisomerismo , TemperaturaRESUMO
OBJECTIVE: To quantify vascular smooth muscle polyploidy and growth kinetics in aortic cells from stroke-prone spontaneously hypertensive rats (SHRSP) and from normotensive Wistar-Kyoto (WKY) rats, and to examine the effects of treatment with the angiotensin converting enzyme (ACE) inhibitor perindopril on these parameters. DESIGN: The following experimental groups were used: young (age < 20 weeks) and old (age > 20 weeks) untreated WKY rats and untreated SHRSP; SHRSP treated with perindopril, and age- and sex-matched control SHRSP; and SHRSP treated with hydralazine and hydrochlorothiazide and age- and sex-matched control SHRSP. The effects of treatment of the SHRSP with perindopril for 30 days on vascular smooth muscle polyploidy and growth kinetics were measured and compared with the effects of equivalent antihypertensive doses of hydralazine and hydrochlorothiazide. METHODS: Vascular smooth muscle polyploidy was measured using flow-cytometry DNA analysis of freshly harvested cells. Growth curves were performed on cultured aortic cells. Plasma renin activity was measured by an antibody-trapping method, plasma angiotensin II (Ang II) by radioimmunoassay and plasma ACE activity by a colorimetric method. Cardiac hypertrophy was evaluated by measuring the heart weight:body weight and left ventricle + septum weight:body weight ratios. RESULTS: The SHRSP had markedly and significantly elevated G2 + M phase of the cell cycle. Treatment with perindopril resulted in a significant reduction in polyploidy in the SHRSP, whereas treatment with hydralazine and hydrochlorothiazide had no effect on the percentage of cells in the G2 + M phase of the cell cycle. The regression of polyploidy after treatment with perindopril was associated with a significant reduction in the concentration of Ang II and ACE activity, and with a significant regression of cardiac hypertrophy. Increased mitogenesis of cultured vascular smooth muscle cells from the SHRSP was not altered by treatment with perindopril. CONCLUSIONS: ACE inhibition reduces vascular smooth muscle polyploidy in large conduit arteries. This type of vascular protection is mediated by the reduced Ang II and possibly by increased kinins level, rather than by the hypotensive effect alone.
Assuntos
Hipertensão/patologia , Indóis/farmacologia , Músculo Liso Vascular/patologia , Poliploidia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Angiotensinas/sangue , Animais , Aorta/patologia , Pressão Sanguínea , Núcleo Celular/patologia , Células Cultivadas , Feminino , Citometria de Fluxo , Frequência Cardíaca , Hipertensão/metabolismo , Masculino , Peptidil Dipeptidase A/sangue , Perindopril , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Renina/sangueRESUMO
We compared Optisol and DexSol, two chondroitin-sulfate-based media for corneal storage at 4 degrees C, by transplanting 31 donor cornea pairs (one cornea stored in Optisol and its mate in DexSol for 20 to 134 hours) into 31 pairs of recipients (62 patients). All grafts were clear 1 year after transplantation except for one primary donor failure (Optisol group). Optisol-stored corneas were significantly thinner than DexSol-stored corneas after cardinal suture placement (0.64 mm vs 0.76 mm) and at the end of surgery (0.69 mm vs 0.78 mm); at all points afterward through 1 year the two groups did not differ. The activity of two lysosomal enzymes released into the media during storage, alpha-mannosidase and alpha-glucosidase, was lower in the Optisol group. Epithelial status and all endothelial morphometric parameters, except the figure coefficient at 1 year, did not differ between the two groups before surgery and 3, 6, and 12 months after surgery. Mean endothelial cell loss at 1 year was 15% for the Optisol group and 21% for the DexSol group (P = .22). Thus, Optisol-stored corneas were thinner during surgery than DexSol-stored corneas and there was less lysosomal enzyme activity in the Optisol medium after tissue storage. There were no significant differences in postoperative clinical or endothelial morphometric parameters, however.
Assuntos
Córnea , Meios de Cultura Livres de Soro , Sobrevivência de Enxerto , Ceratoplastia Penetrante , Preservação de Órgãos , Adulto , Idoso , Contagem de Células , Sulfatos de Condroitina , Misturas Complexas , Córnea/metabolismo , Criopreservação , Dextranos , Método Duplo-Cego , Endotélio Corneano/patologia , Feminino , Gentamicinas , HEPES , Humanos , Masculino , Manosidases/metabolismo , Compostos Orgânicos , Estudos Prospectivos , Resultado do Tratamento , alfa-Glucosidases/metabolismoRESUMO
Topical fibronectin was evaluated for the treatment of keratoconjunctivitis sicca in a multicenter, double-masked, controlled study in which 272 patients were randomly assigned to treatment. Patients with documented clinical evidence of keratoconjunctivitis sicca received either fibronectin, a vehicle alone, or a commercially available artificial tear. Evaluation at baseline, 21, 42, and 63 days consisted of patient self-evaluation of symptoms, rose bengal and fluorescein staining, tear breakup time, Schirmer's testing, and conjunctival impression cytology. Although all groups showed improvements in most study variables during the course of the study, there were no statistically significant differences found between any of the groups. Topical fibronectin does not appear to be more effective than artificial tears in the treatment of keratoconjunctivitis sicca.
Assuntos
Fibronectinas/uso terapêutico , Ceratoconjuntivite Seca/tratamento farmacológico , Idoso , Método Duplo-Cego , Feminino , Fluorofotometria , Humanos , Ceratoconjuntivite Seca/fisiopatologia , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas/uso terapêutico , Placebos , CicatrizaçãoRESUMO
PURPOSE: We sought to evaluate the efficacy of topical fibronectin ophthalmic solution, containing 3.5 mg/ml of human fibronectin, in the treatment of persistent epithelial defects of the cornea. METHODS: In a double-masked, randomized clinical trial, patients with a persistent, corneal epithelial defect of at least 14 days in duration, and at least 2 mm in width along the larger axis, were sought from the practices of 38 clinical investigators. After a 14-day washout period, 65 patients were randomly assigned to one of three treatment groups. One group (n = 20) received fibronectin drops; the second (n = 23) received drops of the vehicle from the fibronectin solution; and the third (n = 22) received a placebo. RESULTS: After 21 days of treatment, there was no difference in percentage reduction of the corneal epithelial defect size; the average percentage of reduction of defect area ranged from 46.5% to 54.3%. Fibronectin treatment showed a beneficial effect for patients with larger baseline defects (10 mm2 or greater in area); however, no such effect was observed among patients with smaller defects. Defect duration before treatment had a significant effect on outcome (P = .007); defects of longer duration were less likely to decrease in size over the course of the study. CONCLUSIONS: All three treatment groups showed similar reductions in defect size; therefore, this study provides no support for the efficacy of fibronectin treatment of persistent, corneal epithelial defects. Defect duration showed a negative association with reduction in defect size. Because strict control of topical applications during the washout and treatment periods resulted in beneficial responses, physicians should carefully consider the topical medications used by patients who have persistent, corneal epithelial defects.
Assuntos
Doenças da Córnea/tratamento farmacológico , Fibronectinas/administração & dosagem , Administração Tópica , Adulto , Doenças da Córnea/complicações , Doenças da Córnea/patologia , Método Duplo-Cego , Epitélio/efeitos dos fármacos , Epitélio/patologia , Feminino , Fibronectinas/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas , PrognósticoRESUMO
PURPOSE: To evaluate the safety and preliminary efficacy of a novel visual prosthetic device, the Implantable Miniature Telescope, IMT (by Dr Isaac Lipshitz) (IMT), in a phase I trial in patients with significant bilateral central vision impairment from late-stage age-related macular degeneration (AMD). The IMT is designed to reduce the relative size of the scotoma by rendering enlarged (threefold) central visual field images over the central and peripheral retina. DESIGN: Prospective, multicenter, open-label clinical trial. METHODS: In this prospective, multicenter phase I trial, 14 patients aged 60 or older with bilateral geographic atrophy or disciform scar AMD, cataract, and best-corrected visual acuity (BCVA) between 20/80 and 20/400 had an IMT implanted in one eye. Distance and near BCVA, endothelial cell density, and quality of life, measured as activities of daily life (ADL), were evaluated preoperatively and postoperatively. RESULTS: At 12 months, 10 (77%) of 13 patients gained 2 more lines of either distance or near BCVA, and eight (62%) of 13 patients gained 3 or more lines in either distance or near BCVA. Mean endothelial cell density decreased by 13%. All adverse events resolved without sequelae. ADL scores improved in the majority of patients. CONCLUSION: The results of this phase I trial support further evaluation of the IMT in a larger study population with late-stage AMD. A phase II/III trial is in progress.
Assuntos
Implante de Lente Intraocular , Lentes Intraoculares , Degeneração Macular/cirurgia , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Contagem de Células , Endotélio Corneano/patologia , Feminino , Humanos , Complicações Intraoperatórias , Degeneração Macular/complicações , Masculino , Óptica e Fotônica/instrumentação , Complicações Pós-Operatórias , Estudos Prospectivos , Qualidade de Vida , Segurança , Transtornos da Visão/etiologia , Transtornos da Visão/cirurgia , Acuidade Visual , Campos VisuaisRESUMO
The structure and composition of living small blood vessels can be studied in great detail in three dimensions using confocal microscopy. Individual cells and their components can be visualised by vital dyes for the nucleus, cytoplasm or extracellular space. Specific ligands can then localise individual components such as membrane receptors with great precision. Cell function is unaffected, allowing the study, in real time, of the changing relation and contribution to vascular contraction or dilatation of different cell types particularly smooth muscle, endothelium and adventitia. This allows not only visualisation but quantification, using image analysis software. These techniques will be of particular value in assessing the contribution of form to function in pathological situations such as vascular remodelling in hypertension.
Assuntos
Vasos Sanguíneos/ultraestrutura , Animais , Vasos Sanguíneos/efeitos dos fármacos , Corantes , Microscopia Confocal/métodos , Coelhos , RatosRESUMO
Flow cytometry DNA analysis has been used to measure the percentage of aortic vascular smooth muscle cells in G2 + M phase of the cell cycle in mature stroke-prone spontaneously hypertensive rats (SHRSP). The effects of three different pharmacological interventions on the cell cycle parameters have also been studied. Vascular smooth muscle cells isolated from SHRSP have significantly elevated G2 + M phase of the cell cycle compared with cells from the normotensive reference strain, Wistar-Kyoto (WKY). This observation reflects an increased tetraploid and octaploid cell populations in vivo. Treatment with a combination of hydralazine and hydrochlorothiazide had no effect on the percentage of cells in G2 + M phase of the cell cycle. Treatments with angiotensin converting enzyme inhibitor, perindopril or AT1 receptor antagonist, losartan, resulted in an equivalent blood pressure-lowering effect to that obtained with hydralazine/hydrochlorothiazide. In contrast to hydralazine/hydrochlorothiazide, these two treatments resulted in a highly significant regression of vascular smooth muscle polyploidy in the SHRSP. We hypothesise that angiotensin II plays an important role in cell cycle regulation in that, alone or in conjunction with one of the inhibitory proteins, it is able to stop the cell cycle progression after endoduplication but before the cytoplasmic division. Pharmacological interventions which remove an excess of angiotensin II may allow the cells to re-enter the cell cycle thus resulting in the regression of vascular smooth muscle polyploidy and improved arterial compliance.
Assuntos
Angiotensina II/fisiologia , Hipertensão/genética , Hipertensão/fisiopatologia , Músculo Liso Vascular/fisiologia , Ploidias , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Compostos de Bifenilo/farmacologia , Ciclo Celular , Humanos , Imidazóis/farmacologia , Losartan , Modelos Cardiovasculares , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/patologia , Tetrazóis/farmacologiaRESUMO
Twelve mercapturic acids derived from saturated and unsaturated aliphatic and aromatic isothiocyanates were synthesised, by adding isothiocyanate to a solution of N-acetyl-L-cysteine and sodium bicarbonate, in a typical yield of 77%. Isothiocyanates were synthesised first by adding the corresponding alkyl bromide to phthalimide potassium salt. The obtained N-alkyl-phthalimide was hydrazinolysed yielding the alkyl amine, which subsequently was reacted with thiophosgene yielding the isothiocyanate with an overall yield of 16%. Mercapturic acids in urine can serve as a biomarker of intake to determine the health promoting potential of isothiocyanates present in cruciferous vegetables.
Assuntos
Acetilcisteína/análogos & derivados , Isotiocianatos/química , Acetilcisteína/síntese química , Acetilcisteína/urina , Biomarcadores/urina , Cromatografia Líquida de Alta Pressão , Dieta , Glucosinolatos/química , Humanos , Isotiocianatos/metabolismo , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Tiocianatos/metabolismo , Tiocianatos/urina , Verduras/química , Verduras/metabolismoRESUMO
Carbohydrate based syntheses of azasugars with unusual configurations viz. 1,5-dideoxy-1,5-imino-L-gulitol (L-guloDNJ) and 1,5-dideoxy-1,5-imino-L-talitol (L-taloDNJ) are reported, from D-mannose and D-fructose, respectively. The key steps in both syntheses involved reductive aminative cyclizations. Thus, L-guloDNJ was obtained by reduction of 2,3;4,6-di-O-isopropylidene-5-O-p-toluenesulfonyl-D-mannononitrile with LiAlH(4) in DME to give the protected azasugar which upon hydrolysis with HCl afforded crystalline L-guloDNJ as the HCl salt in 29% overall yield. Reduction of 6-azido-1-O-tert-butyldimethylsilyl-2,3-O-isopropylidene-beta-D-ribohexulofuranose obtained from D-fructose in six steps, followed by treatment with HCl, afforded L-taloDNJ as an HCl salt in approximately 10% overall yield.
Assuntos
1-Desoxinojirimicina/análogos & derivados , 1-Desoxinojirimicina/síntese química , 1-Desoxinojirimicina/química , Estrutura Molecular , EstereoisomerismoAssuntos
Meios de Cultura Livres de Soro , Contaminação de Medicamentos/prevenção & controle , Estreptomicina , Idoso , Sulfatos de Condroitina , Misturas Complexas , Dextranos , Gentamicinas , Sobrevivência de Enxerto , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Ceratoplastia Penetrante , Pessoa de Meia-Idade , Preservação de ÓrgãosRESUMO
The immunopharmacologic effects of Isoprinosine (INPX) have been associated with clinical benefit to the patient in a number of conditions characterized by immunodeficiency of diverse etiology. Immunodepressed homosexuals at risk of developing acquired immunodeficiency syndrome (AIDS) treated with placebo or INPX experienced an increase in the function and number of immunocompetent cells associated with clinical improvement. A multicenter trial designed to confirm these results has demonstrated that INPX produced an increase in natural killer (NK)-cell activity, total T cells, and T-helper cells, with certain effects persisting for months after completion of the 28-day treatment period. INPX-treated patients also experienced clinical improvement and decreased incidence of progression to AIDS. The administration of INPX for longer periods to patients with frank AIDS under a compassionate-use protocol has also proved useful. Clinical benefit associated with INPX treatment has been demonstrated in other patients with a depressed immune response, such as aged patients, cancer patients, severely burned patients, ill patients, and surgery patients. This program of clinical trials supports the therapeutic use of INPX in the treatment of AIDS and other acquired immunodeficiencies of clinical importance.
Assuntos
Complexo Relacionado com a AIDS/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Síndromes de Imunodeficiência/tratamento farmacológico , Inosina Pranobex/uso terapêutico , Inosina/análogos & derivados , Humanos , Síndromes de Imunodeficiência/etiologiaRESUMO
This study determines whether endothelial survival after penetrating keratoplasty is improved by adding the mitogens, human epidermal growth factor (hEGF), and human insulin to a chondroitin-sulfate-based corneal storage medium. It is a multicenter, prospective, double-masked, randomized trial that compares endothelial survival of human corneal transplants using donor corneas that have been stored in one of two media: DexSol (CSM with 1% dextran) or DexSol containing recombinant hEGF and human insulin. This article describes the study design and entry characteristics of the 105 recipient pairs. Each donor pair of corneas is transplanted on the same day into recipients who are matched by diagnosis and procedure. Clinical parameters assessed on day 1, week 1, and 3, 6 and 12 months postoperatively include graft clarity, epithelial integrity, corneal thickness, visual acuity, and intraocular pressure. Postoperative endothelial survival for both groups will be determined by morphometric analysis of endothelial cell images before storage and at 3, 6, and 12 months postoperatively. Such analysis will also identify differences in polymegathism (cell size) or pleomorphism (cell shape).
Assuntos
Endotélio Corneano/efeitos dos fármacos , Fator de Crescimento Epidérmico/farmacologia , Insulina/farmacologia , Ceratoplastia Penetrante , Adulto , Idoso , Idoso de 80 Anos ou mais , Sobrevivência Celular/efeitos dos fármacos , Método Duplo-Cego , Feminino , Humanos , Pressão Intraocular/efeitos dos fármacos , Ceratoplastia Penetrante/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas Recombinantes , Projetos de Pesquisa , Estatística como Assunto , Doadores de Tecidos , Preservação de Tecido/métodos , Acuidade VisualRESUMO
We have used nuclear fluorescent dyes to develop a technique for the study of vascular structure and function. Nuclear stained blood vessels, viewed with the appropriate filter sets, can be studied in great detail. Only the nuclei of the cells which form the walls are visible and so their positions relative to one another as well as their viability can be quickly assessed. The dyes are not toxic, therefore when the vessel contracts or relaxes, the changes in position of the nuclei can be monitored. In this paper we describe two original applications of fluorescent nuclear dyes in vascular research.
Assuntos
Núcleo Celular , Corantes Fluorescentes , Músculo Liso Vascular/anatomia & histologia , Músculo Liso Vascular/fisiologia , Animais , Aorta/anatomia & histologia , Aorta/fisiologia , Benzimidazóis , Sobrevivência Celular , Masculino , Artérias Mesentéricas/anatomia & histologia , Artérias Mesentéricas/fisiologia , Contração Muscular , Ratos , Ratos Endogâmicos , Coloração e RotulagemRESUMO
The rabbit isolated lateral saphenous vein (RLSV) has a heterogeneous population of alpha-adrenoceptors. Responses to electrical field stimulation, in the presence of cocaine, exhibit both alpha 1- and alpha 2-adrenoceptor-mediated components. The present study examined sympathetic neuroeffector transmission and the response to exogenous catecholamines after inhibition of nitric oxide (NO) synthesis with N omega-nitro-L-arginine methyl ester (L-NAME). A comparison of the response in the presence and absence of a functional endothelium was also carried out. L-NAME potentiated the first and second components of the response to nerve stimulation on the order of 300 and 500%, respectively. L-NAME also significantly potentiated responses to norepinephrine (NE), phenylephrine (PE), and UK 14304. Selective antagonism of the first phase was seen with prazosin (alpha 1-antagonist, 0.1 microM) and the second phase with rauwolscine (alpha 2-antagonist, 1 microM). In the presence of L-NAME, the remaining (uninhibited) components were potentiated. Removal of endothelial function induced by gentle rubbing of the intimal surface abolished potentiation to exogenous NE, PE, and UK14304 by L-NAME. However, a significant degree of potentiation of the neurogenic response was observed in the rubbed tissues in response to L-NAME. This suggests that there may be a nonendothelial source of NO that can modulate the neurogenic response to electrical field stimulation.
Assuntos
Arginina/análogos & derivados , Óxido Nítrico/metabolismo , Veia Safena/inervação , Sistema Nervoso Simpático/fisiologia , Transmissão Sináptica , Agonistas alfa-Adrenérgicos/farmacologia , Animais , Arginina/farmacologia , Tartarato de Brimonidina , Estimulação Elétrica , Técnicas In Vitro , Masculino , NG-Nitroarginina Metil Éster , Norepinefrina/farmacologia , Fenilefrina/farmacologia , Quinoxalinas/farmacologia , Coelhos , Receptores Adrenérgicos alfa/metabolismo , Transmissão Sináptica/efeitos dos fármacosRESUMO
PURPOSE: The ability of DexSol medium, supplemented with two growth factors, human epidermal growth factor (hEGF) and human insulin, to improve long-term endothelial survival after penetrating keratoplasty was evaluated in a multi-center, randomized, prospective, double-masked clinical trial. METHODS: Donor cornea pairs, one stored in DexSol and the other in DexSol with hEGF (10 ng/ml) and human insulin (10 micrograms/ml) (ProCell), were transplanted into 105 pairs of recipients matched by diagnosis and procedure and followed postoperatively for graft and endothelial survival. RESULTS: No primary donor failures occurred in either group. Graft clarity did not differ between the ProCell and DexSol groups at all postoperative periods: 3 months (98% versus 99%), 6 months (94% versus 98%), and 1 year (95% versus 97%), respectively. Postoperative complications (e.g., glaucoma, rejection) occurred with comparable frequencies in both groups. Mean endothelial cell loss did not significantly differ between the ProCell and DexSol groups at 3 months (5.7% versus 5.1%), 6 months (8.1% versus 10.1%), and 1 year (12.3% versus 15.6%), respectively. Similarly, there were no clinically and statistically significant differences in other endothelial morphometric parameters. CONCLUSIONS: The use of corneas stored in DexSol medium with added hEGF and insulin in corneal transplantation resulted in a safety and efficacy profile comparable with that observed in patients receiving DexSol-stored corneas; however, there were no clinically and statistically significant differences in postoperative endothelial morphometric parameters.
Assuntos
Córnea , Criopreservação/métodos , Meios de Cultura Livres de Soro , Fator de Crescimento Epidérmico , Insulina , Preservação de Órgãos/métodos , Adulto , Idoso , Contagem de Células , Sobrevivência Celular/fisiologia , Sulfatos de Condroitina , Método Duplo-Cego , Endotélio Corneano/patologia , Feminino , Seguimentos , Glicosídeo Hidrolases/metabolismo , Sobrevivência de Enxerto/fisiologia , HEPES , Humanos , Ceratoplastia Penetrante , Masculino , Compostos Orgânicos , Complicações Pós-Operatórias , Estudos ProspectivosRESUMO
BACKGROUND: Sustained-release, intraocular implants that deliver ganciclovir are an alternative method for the treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome (AIDS). METHODS: We conducted a randomized study of 188 patients with AIDS and newly diagnosed cytomegalovirus retinitis. The patients were randomly assigned to treatment with an implant delivering 1 microg of ganciclovir per hour, an implant delivering 2 microg of ganciclovir per hour, or intravenous ganciclovir. The primary outcome we studied was progression of cytomegalovirus retinitis. RESULTS: The median time to progression of retinitis was 221 days with the 1-microg-per-hour implant (75 eyes), 191 days with the 2-microg-per-hour implant (71 eyes), and 71 days with ganciclovir administered intravenously (76 eyes; P<0.001). The risk of progression of retinitis was almost three times as great among patients treated with intravenous ganciclovir as among those treated with a ganciclovir implant (risk ratio, 2.8; P<0.001). However, the risk of disease in the initially uninvolved eye was lower with intravenous ganciclovir than with a ganciclovir implant (risk ratio, 0.5; P=0.19). Patients treated with intravenous ganciclovir were also less likely to have extraocular cytomegalovirus infections (0, vs. 10.3 percent in the two implant groups; P=0.04). CONCLUSIONS: For the treatment of cytomegalovirus retinitis, the sustained-release ganciclovir implant is more effective than intravenous ganciclovir, but patients treated with a ganciclovir implant alone remain at greater risk for the development of cytomegalovirus disease outside of the treated eye.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antivirais/administração & dosagem , Retinite por Citomegalovirus/tratamento farmacológico , Ganciclovir/administração & dosagem , Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Síndrome da Imunodeficiência Adquirida/mortalidade , Adulto , Retinite por Citomegalovirus/mortalidade , Progressão da Doença , Implantes de Medicamento , Feminino , Humanos , Injeções Intravenosas , Masculino , Modelos de Riscos Proporcionais , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: Hypertension is a major risk factor for stroke and is associated with alterations in vascular structure and function. The aim of this study was to determine vascular function, wall morphology, and vascular smooth muscle cell (VSMC) arrangement in basilar arteries from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive control strain Wistar-Kyoto rats (WKY). The effect of perindopril treatment on SHRSP structure and function was also assessed. METHODS: VSMC orientation was determined with laser-scanning confocal microscopy and computer-assisted image processing in basilar arteries stained with 5(6)-carboxyfluorescein (wavelengths: excitation, 488; emission, 515) or propidium iodide (excitation, 529; emission, 550). Measurements of wall morphology and functional responses to serotonin and KCl were assessed with wire myography. RESULTS: In the WKY basilar arteries, VSMCs were uniformly oriented perpendicular to the longitudinal axis of the vessel, whereas in the SHRSP there were localized foci of VSMC geometric disorganization, with a significant deviation from 90 degrees. The SHRSP basilar arteries also showed structural remodeling and reduced contractile responses to serotonin and KCl. Perindopril treatment normalized blood pressure, prevented wall morphology alterations, and improved function but had no effect on VSMC disorganization. CONCLUSIONS: This is the first demonstration of lesions of VSMC geometric disorganization in a cerebral artery from a stroke-prone genetically hypertensive rat strain. These structural abnormalities are independent of blood pressure. Their functional sequel may play a role in the pathogenesis of stroke in this model.