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There is limited evidence on the blood pressure (BP)-lowering effect of esaxerenone on home BP, including nighttime BP. Using two newly developed nocturnal home BP monitoring devices (brachial and wrist), this multicenter, open-label, prospective study investigated the nighttime home BP-lowering effect of esaxerenone in patients with uncontrolled nocturnal hypertension being treated with an angiotensin receptor blocker (ARB) or calcium-channel blocker (CCB). In total, 101 patients were enrolled. During the 12-week study period, change in nighttime home systolic/diastolic BP from baseline to end of treatment measured by the brachial device was -12.9/-5.4 mmHg in the total population and -16.2/-6.6 and -10.0/-4.4 mmHg in the ARB and CCB subcohorts, respectively (all p < 0.001). For the wrist device, the change was -11.7/-5.4 mmHg in the total population and -14.6/-6.2 and -8.3/-4.5 mmHg in each subcohort, respectively (all p < 0.001). Similar significant reductions were shown for morning and bedtime home BP and office BP. Urinary albumin-to-creatinine ratio, N-terminal pro-brain natriuretic peptide, and cardio-ankle vascular index improved in the total population and each subcohort. Incidences of treatment-emergent adverse events (TEAEs) and drug-related TEAEs were 38.6% and 16.8%, respectively; most were mild or moderate. The most frequent drug-related TEAEs were associated with serum potassium elevation (hyperkalemia, 9.9%; blood potassium increased, 3.0%); however, no new safety concerns were raised. Esaxerenone was effective in lowering nighttime home BP as well as morning and bedtime home BP and office BP, safe, and showed organ-protective effects in patients with uncontrolled nocturnal hypertension. Caution is warranted regarding elevated serum potassium levels. This study investigated the effect of esaxerenone on nighttime home BP and organ damage (UACR and NT-proBNP) in patients with uncontrolled nocturnal hypertension despite treatment with an ARB or CCB. Our results show that safe 24-h BP control and organ protection are possible with esaxerenone.
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Anti-Hipertensivos , Hipertensão , Humanos , Pressão Sanguínea/fisiologia , Anti-Hipertensivos/efeitos adversos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Estudos Prospectivos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Potássio , Monitorização Ambulatorial da Pressão ArterialRESUMO
OBJECTIVES: The purpose of this study was to elucidate how masticatory muscles are involved in the generation of occlusal force. MATERIALS AND METHODS: The experiment was conducted by fabricating an experimental apparatus for a unilateral occlusion model with the masticatory muscles imparted. The experimental apparatus was fabricated by enlarging the lateral photograph of a dried adult skull specimen 3.5 times larger than that of a standard adult and drawing the outlines of the maxilla and mandible, canines and molars of the upper and lower jaws, and temporomandibular joint on a wooden board. The masticatory muscles used in the experiment were the masseter muscle, the temporalis muscle (anterior and posterior muscle bundles), and the lateral pterygoid muscle. For the measurement of the contractile force of the masticatory muscle, we used the spring scale. For the food, we used cut plastic cylinders. RESULTS: The results of the experiment revealed the following: First, the occlusal force was generated under the condition that the contraction forces of all the masticatory muscles were balanced. Second, when the occlusal force was applied to food, the occlusal planes of the upper and lower jaws were parallel. Third, the occlusal force occurred perpendicular to the occlusal plane. Fourth, the occlusal force was generated with a force greater than the contraction force of the individual masticatory muscles. And finally, even if occlusal force was applied to the food, the occlusal force did not load the temporomandibular joint. CONCLUSION: Occlusal force is not generated by the action of a single masticatory muscle but under the balanced contractile force of all masticatory muscles. The occlusal force then emerges with a force greater than the contraction force of all the masticatory muscles, and its direction occurs perpendicular to the occlusal plane.
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Força de Mordida , Músculo Masseter , Músculos da Mastigação , Músculos Pterigoides/fisiologia , MaxilaRESUMO
Purpose: We assessed the effect of rebamipide ophthalmic solution on corneal epithelial injury due to benzalkonium chloride (BAK) by fluorescein (FL) staining and corneal resistance (CR). Methods: After determining the absence of corneal epithelial damage by FL and CR, rebamipide ophthalmic solution (50 µL) was instilled five times, each interspaced by 5 min, into one eye of mature New Zealand white rabbits, and likewise physiological saline was instilled into the contralateral eye as the control. After 30 min, eyes were similarly treated with one of the following solutions: BAK solution 0.02%, latanoprost ophthalmic solution (0.02% BAK), or latanoprost ophthalmic solution without BAK. The presence of corneal epithelial damage was quantitated at 10, 30, and 60 min by CR after the last instillation. FL staining was also performed at 60 min after the last instillation. Results: CR ratios (%) at 60 min after the last instillation in rebamipide/BAK and rebamipide/latanoprost (0.02% BAK) groups were significantly increased by 18.3% and 25.6% compared with saline/BAK and saline/latanoprost (0.02% BAK) groups, respectively (P < 0.05). Findings by FL staining were consistent with those by CR; BAK and latanoprost with BAK groups were positive, and eyes with the most severe area and density of corneal epithelial damage (A2D2) were in the saline/BAK group. Conclusion: The rebamipide ophthalmic solution reduces the severity of corneal epithelial injury caused by BAK, an ophthalmic solution preservative.
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Alanina/análogos & derivados , Antioxidantes/farmacologia , Compostos de Benzalcônio/farmacologia , Epitélio Corneano/efeitos dos fármacos , Epitélio Corneano/lesões , Conservantes Farmacêuticos/farmacologia , Quinolonas/farmacologia , Alanina/farmacologia , Animais , Quimioterapia Combinada , Latanoprosta/farmacologia , Masculino , Coelhos , Distribuição AleatóriaRESUMO
OBJECTIVES: It is common to treat type 2 diabetes by regular injections of insulin. We compared the efficacy and safety of twice-daily administration of short-acting, premixed, and long-acting insulins. METHODS: This was a multi-center, randomized, open-label, 52-week study. Patients were randomized to administer twice daily short-acting analog insulin (Aspart) plus a sulfonylurea (SU), premixed 70/30 analog insulin (Mix), or long-acting insulin (Detemir) plus a glinide derivative. RESULTS: Twelve (mean baseline HbA1c 9.86±1.71%), eight (9.24±1.14%), and eight (11.26±1.81%) patients were treated with Aspart, Mix, or Detemir, respectively, for 52 weeks. After 12 weeks, the reductions in HbA1c were similar in the groups. A further significant reduction in HbA1c occurred between weeks 12 and 52 in the Detemir, but not the Aspart or Mix groups. After 52 weeks, the target of an HbA1c <7.4% was achieved in 16.7% of the Aspart group, 37.5% of the Mix group, and 12.5% of the Detemir group (no significant differences among the three groups by χ2 analysis). The mean changes from baseline in blood glucose concentration measured after breakfast, and before and after dinner, were also similar in each group. CONCLUSIONS: Early and meaningful reductions in HbA1c were achieved by twice-daily administration of a premix, aspart plus an SU, and detemir plus a glinide, without severe hypoglycemia or an increase in body mass. However, the target HbA1c was achieved in relatively few participants, perhaps due to an insufficient dose of insulin or the small study size.
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AIMS/INTRODUCTION: The present multicenter, cross-sectional survey was initiated to evaluate self-monitoring of blood glucose (SMBG)-associated mental distress among patients with diabetes. MATERIALS AND METHODS: The survey was carried out in patients with type 1 diabetes and type 2 diabetes using SMBG recruited from 42 medical institutions. Profiles of Mood States 2 and diabetes therapy-related quality of life questionnaires were used to evaluate mood status and health-related quality of life. Two original questionnaires were also developed to evaluate SMBG 'importance,' 'painfulness' and 'confidence' among patients, and to evaluate physician attitudes to SMBG use. RESULTS: Questionnaires from 517 type 1 diabetes and 1,648 type 2 diabetes patients showed that 46.0% of type 1 diabetes and 37.5% of type 2 diabetes patients reported 'painfulness,' and that these patients reporting 'painfulness' showed significantly higher Profiles of Mood States 2 scores, lower diabetes therapy-related quality of life scores and higher glycated hemoglobin compared with those not reporting 'painfulness,' whereas the number of their daily SMBG tests were comparable. Patients reporting 'painfulness' also reported that SMBG use was significantly less important. Whether or not patients recognized the importance of SMBG use was well correlated with the frequency of physicians checking patient diaries. CONCLUSIONS: Type 1 diabetes and type 2 diabetes patients reporting 'painfulness' in SMBG use had more mental distress, lower health-related quality of life and higher glycated hemoglobin regardless of their number of daily SMBG tests. The importance of SMBG use was recognized less by patients experiencing pain, and the importance of SMBG use was recognized more in medical institutions in which physicians regularly checked SMBG diaries to provide meaningful feedback to patients in clinical settings.
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Automonitorização da Glicemia/psicologia , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/psicologia , Diabetes Mellitus Tipo 2/psicologia , Qualidade de Vida , Estresse Psicológico/psicologia , Adulto , Idoso , Estudos Transversais , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estresse Psicológico/sangue , Estresse Psicológico/epidemiologia , Inquéritos e QuestionáriosRESUMO
We analyzed the changes of glycemic control over 12 months and the factors influencing blood glucose in 162 Japanese patients with type 2 diabetes having inadequate glycemic control despite sulfonylurea-based therapy who received add-on sitagliptin. Hemoglobin A1c (HbA1c) decreased significantly after 4 weeks of treatment, and this improvement was maintained for 1 year, although HbA1c was slightly higher in week 52 than in week 24. Comparison of the patients showing a ≥0.4% increase of HbA1c between weeks 24 and 52 (n = 57) with the others (n = 105) showed a significant difference in the change of bodyweight, as well as the dose of glibenclamide (both P < 0.01). Although combined therapy with sitagliptin and a sulfonylurea seems to be effective for at least 1 year, blood glucose levels are more likely to increase again in patients who show greater weight gain after 24 weeks of treatment and those receiving a higher dose of glibenclamide.
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The solid-state (13)C NMR spectra of various guest hydrocarbons (methane, ethane, propane, adamantane) in clathrate hydrates were measured to elucidate the local structural environments around hydrocarbon molecules isolated in guest-host frameworks of clathrate hydrates. The results show that, depending on the cage environment, the trends in the (13)C chemical shift and line width change as a function of temperature. Shielding around the carbons of the guest normal alkanes in looser cage environments tends to decrease with increasing temperature, whereas shielding in tighter cage environments tends to increase continuously with increasing temperature. Furthermore, the (13)C NMR line widths suggest, because of the reorientation of the guest alkanes, that the local structures in structure II are more averaged than those in structure I. The differences between structures I and II tend to be very large in the lower temperature range examined in this study. The (13)C NMR spectra of adamantane guest molecules in structure H hydrate show that the local structures around adamantane guests trapped in structure H hydrate cages are averaged at the same level as in the α phase of solid adamantane.
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Furanos/química , Hidrocarbonetos/química , Isótopos de Carbono , Furanos/síntese química , Espectroscopia de Ressonância Magnética/normas , Padrões de Referência , Água/químicaRESUMO
PURPOSE: To investigate the safety of five types of antiglaucoma prostaglandin analog ophthalmic formulations, and to clarify their differences in accordance with contained additives (preservatives and surface-active agents). METHODS: THE FOLLOWING FIVE TYPES OF OPHTHALMIC SOLUTIONS AND THREE TYPES OF ADDITIVES WERE INVESTIGATED: latanoprost (Xalatan(®); latanoprost), tafluprost (Tapros(®); tafluprost), bimatoprost (Lumigan(®); bimatoprost), travoprost (Travatan(®); travoprost), travoprost (Travatan Z(®); travoprost-Z), benzalkonium chloride (BAK), polyoxyethylene hardening castor oil 40 (HCO-40), and polysorbate 80 (P-80). These experimental solutions were exposed to the cultured cells of a rabbit-derived corneal cell line for a certain time, and the exposure time causing 50% cell damage (CD50), indicated by the ratio of viable cells to total cells was calculated (in vitro). In addition, corneal resistance (CR) was measured and CR ratio (post-treatment CR/pretreatment CR × 100) was calculated (in vivo). RESULTS: CD50 of each ophthalmic solution was the longest with tafluprost, followed by travoprost-Z, bimatoprost, travoprost, and latanoprost. CD50 of 0.005%, 0.01%, and 0.02% BAK was 14.5 minutes, 8.1 minutes, and 4.0 minutes, respectively. The number of viable cells decreased to 60%, 8 minutes after exposure with HCO-40, and 30 minutes after being exposed to P-80. The CR ratio was 81.0% with travoprost and 82.0% with latanoprost, indicating a significant posttreatment reduction of CR (P < 0.05). The CR ratio did not decrease after treatment with tafluprost, travoprost-Z, or bimatoprost. The CR ratio of 0.005%, 0.01%, and 0.02% BAK was 105.0%, 90.5%, and 68.7%, respectively, and that of HCO-40 and P-80 was 108.7% and 114.2%, respectively. CONCLUSION: BAK, HCO-40, and P-80 were thought to be involved in corneal injuries caused by each ophthalmic solution. Corneal injuries due to surface action were observed when using HCO-40 and P-80. When HCO-40 was combined with BAK, it induced micellar BAK and reduced corneal injuries by BAK.
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Experimental NMR measurements for (13)C chemical shifts of propane molecules encaged in 16-hedral cages of structure II clathrate hydrate were conducted to investigate the effects of guest-host interaction of pure propane clathrate on the (13)C chemical shifts of propane guests. Experimental (13)C NMR measurements revealed that the clathrate hydration of propane reverses the (13)C chemical shifts of methyl and methylene carbons in propane guests to gaseous propane at room temperature and atmospheric pressure or isolated propane, suggesting a change in magnetic environment around the propane guest by the clathrate hydration. Inversion of the (13)C chemical shifts of propane clathrate suggests that the deshielding effect of the water cage on the methyl carbons of the propane molecule encaged in the 16-hedral cage is greater than that on its methylene carbon.
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Dissociation behavior of methane-ethane mixed gas hydrate coexisting structures I and II at constant temperatures less than 223 K was studied with use of powder X-ray diffraction and solid-state (13)C NMR techniques. The diffraction patterns at temperatures less than 203 K showed both structures I and II simultaneously convert to Ih during the dissociation, but the diffraction pattern at temperatures greater than 208 K showed different dissociation behavior between structures I and II. Although the diffraction peaks from structure II decreased during measurement at constant temperatures greater than 208 K, those from structure I increased at the initial step of dissociation and then disappeared. This anomalous behavior of the methane-ethane mixed gas hydrate coexisting structures I and II was examined by using the (13)C NMR technique. The (13)C NMR spectra revealed that the anomalous behavior results from the formation of ethane-rich structure I. The structure I hydrate formation was associated with the dissociation rate of the initial methane-ethane mixed gas hydrate.
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Etano/química , Metano/química , Gases/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Difração de Pó , TemperaturaRESUMO
PURPOSE: To investigate the protein and mRNA expressions of matrix metalloproteinases (MMPs), gelatinolytic activity and localization of MMP activity in wounds after glaucoma filtration surgery in rabbits. METHODS: Sixty eyes of 30 rabbits were removed 1, 3, 7, 14 and 120 days after the surgery and used for this experiment. Protein and mRNA expressions were analyzed by immunohistochemistry and laser capture microdissection/real-time RT-PCR, respectively. The gelatinolytic activity was analyzed by gelatin zymography and the localization was studied using in situ zymography. RESULTS: By immunohistochemistry, expression of MMP-1, MMP-2, MMP-3, MMP-9 and MT1-MMP was detected in the wounds, most markedly 3 days after the surgery. MMP-positive cells were predominantly macrophages. Expression of MMP-9 and MT1-MMP mRNAs was verified by RT-PCR. Gelatinolytic activities corresponding to proMMP-2 and the active form of MMP-2 were detected in the wounds 3 and 7 days after surgery. In situ zymography localized gelatinolytic activities at the wound site. These activities were almost completely abolished by an MMP inhibitor, indicating that the gelatinolytic activity belongs to metalloproteinases. CONCLUSIONS: MMPs, particularly MMP-2/MT1-MMP, play important roles in the degradation of the extracellular matrix in the wound healing process after glaucoma filtration surgery and may represent an important target for therapeutic intervention after glaucoma filtration surgery.
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Olho/enzimologia , Cirurgia Filtrante , Gelatina/metabolismo , Glaucoma/cirurgia , Metaloproteinases da Matriz/metabolismo , Cicatrização , Animais , Vesícula/etiologia , Vesícula/fisiopatologia , Dissecação/métodos , Olho/patologia , Cirurgia Filtrante/efeitos adversos , Imuno-Histoquímica , Lasers , Macrófagos/enzimologia , Macrófagos/patologia , Metaloproteinase 14 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinases da Matriz/genética , Período Pós-Operatório , RNA Mensageiro/metabolismo , Coelhos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Distribuição TecidualRESUMO
PURPOSE: In this study, we measured the cefotiam dihydrochloride (CTM) concentration in ocular tissue after filtration surgery in rabbit eyes. METHODS: CTM (20 mg/kg body weight) was administered intravenously 30 min before filtration surgery which was performed by double flap procedure on the right eyes of white rabbits. The aqueous humor and serum were extracted at 10 min after surgery and at 30 min, 60 min, and 120 min. Drug concentration in all of the specimens was measured by high performance liquid chromatography (HP-LC). RESULT: The CTM concentrations of aqueous humor in the nonoperated eyes were 0.44 +/- 0.16(mean +/- standard deviation) microg/ml (n = 4) (40 min after intravenous dosage), 0.36 +/- 0.17microg/ml (n = 4) (60 min after intravenous dosage), 0.38 +/- 0.34, microg/ml(n = 3) (90min after intravenous dosage) and 0.27 +/- 0.10 microg/ml (n = 5) (150 min after intravenous dosage). In contrast, CTM concentration in the aqueous humor of the operated eyes was 2.4 +/- 0.95 microg/ml (n = 4) at 10 min after surgery (40 min after intravenous dosage), 2.11 +/- 1.10 microg/ml (n = 4) at 30 min after surgery (60 min after intravenous dosage), 1.18 +/- 0.78 microg/ml (n = 4) at 60 min after surgery (90 min after intravenous dosage) and 0.47 +/- 0.1 microg/ml (n = 5) at 120 min after surgery (150 min after intravenous dosage). The intraocular penetration of CTM at 10 min and at 120 min after filtration surgery was significantly higher in comparison with the drug concentration in the nonoperated eyes (p < 0.05). CONCLUSION: The intraocular penetration of CTM after filtration surgery was much higher in comparison with the drug concentration in the nonoperated eyes. These results may be useful to predict the intraocular penetration of CTM in human eyes after filtration surgery.
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Antibacterianos/farmacocinética , Humor Aquoso/metabolismo , Cefotiam/farmacocinética , Olho/metabolismo , Cirurgia Filtrante , Animais , Cromatografia Líquida de Alta Pressão , Injeções Intravenosas , CoelhosRESUMO
OBJECTIVES: The prevalence of Helicobacter pylori (Hp) infection and the development of gastric cancer are both believed to increase with age in Japan. However, no studies have investigated people older than 65 years in detail. In this study, we investigated the prevalence of Hp infection and gastric cancer in the elderly, and analyzed the influence of both factors on longevity. METHODS: All patients investigated were 65 years old and over. A total of 1877 autopsy cases were used to investigate the prevalence of gastric cancer and colonic cancer. Serum samples were obtained from 644 patients with dyspepsia and analyzed for Hp-IgG antibodies. Of these 644 patients, 63 underwent upper gastrointestinal endoscopies. Five biopsies were obtained and evaluated for the following morphological variables: neutrophils, mononuclear cell, atrophy, and intestinal metaplasia. Hp infection was evaluated histologically and with the (13)C-urea breath test. RESULTS: The prevalence of gastric cancer was significantly lower in subjects older than 85 years. The positive rate of serum Hp-IgG, and Hp infection as detected histologically and by the (13)C-urea breath test, also decreased with age. In Hp(+) patients, the neutrophil score significantly decreased with age. In Hp(-) patients, however, the intestinal metaplasia score significantly increased with age. CONCLUSIONS: The non-infection of Hp itself is not related to longevity in Japanese elderly, because even Hp(-) patients appear to have been infected previously with Hp. The lower prevalence of gastric cancer in the elderly may be due to the disappearance of Hp colonization, which may contribute to longevity in Japanese elderly.
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Infecções por Helicobacter/complicações , Helicobacter pylori/isolamento & purificação , Neoplasias Gástricas/microbiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Infecções por Helicobacter/microbiologia , Humanos , Japão/epidemiologia , Longevidade , Masculino , Prevalência , Neoplasias Gástricas/epidemiologiaRESUMO
Histological and functional changes of the lacrimal gland might be reflected in proteomic patterns in tear fluids. In this study, we carried out a determination of the disease biomarkers in tear fluid for Sjögren's syndrome (SS) and a performance of noninvasive diagnostic test based on the proteomic patterns. Thirty-one SS patients and 57 control subjects were enrolled to this study. Their details were 23 cases with primary SS, 8 with secondary SS, 14 with dry eyes, 22 with miscellaneous ocular diseases, and 21 of healthy volunteers. Protein profiling in tear fluids was identified by surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Multiple protein changes were reproducibly detected in the primary SS group, including 10 potential novel biomarkers. Seven of the biomarkers (2094, 2743, 14191, 14702, 16429, 17453, 17792 m/z) were down-regulated and 3 biomarkers (3483, 4972, 10860 m/z) were up-regulated in primary SS group, comparing to the protein profiles of control subjects. When cutoff value of SS down-score was set less than 0.5, this result yielded 87% sensitivity and 100% specificity. The positive predictive value for this sample set was 100%. There was a significant inverse correlation between SS down-scores and epithelial damages of the ocular surface in primary SS patients. These findings support the potential of proteomic pattern technology in tear fluids as the noninvasive diagnostic test for primary SS.
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Proteínas/análise , Proteômica/métodos , Síndrome de Sjogren/diagnóstico , Lágrimas/química , Biomarcadores/análise , Estudos de Casos e Controles , Oftalmopatias/diagnóstico , Regulação da Expressão Gênica , Humanos , Espectrometria de Massas/métodos , Sensibilidade e EspecificidadeRESUMO
Accumulating evidence suggests that central thyrotropin-releasing hormone (TRH) administration induces gastric erosion 4 h after administration through the vagal nerves. However, early changes in the gastric mucosa during these 4 h have not been described. To assess early changes in the gastric mucosa after intracisternal injection of a stable TRH analog, pGlu-His-(3,3'-dimethyl)-ProNH2 (RX-77368), we measured the blood-to-lumen 51Cr-labeled EDTA clearance and examined the effects of vagotomy, atropine, omeprazole, and hydrochloric acid (HCl) on RX-77368-induced mucosal permeability. A cytoprotective dose of RX-77368 (1.5 ng) did not increase mucosal permeability. However, higher doses significantly increased mucosal permeability. Permeability peaked within 20 min and gradually returned to control levels in response to a 15-ng dose (submaximal dose). Increased mucosal permeability was not recovered after a 150-ng dose (ulcerogenic dose). This increase in permeability was inhibited by vagotomy or atropine. Intragastric perfusion with HCl did not change the RX-77368 (15 ng)-induced increase in permeability, but completely inhibited the recovery of permeability after the peak. Pretreatment with omeprazole did not change the RX-77368 (15 ng)-induced increase in permeability, but quickened the recovery of permeability after the peak. These data indicate that the RX-77368-induced increase in permeability is mediated via the vagal-cholinergic pathway and is not a secondary change in RX-77368-induced acid secretion. Inhibited recovery of permeability on exposure to an ulcerogenic RX-77368 dose or on exposure to HCl plus a submaximal dose of RX-77368 may be crucial for the induction of gastric mucosal lesions by central RX-77368 administration.
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Encéfalo/efeitos dos fármacos , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/fisiologia , Ácido Pirrolidonocarboxílico/análogos & derivados , Ácido Pirrolidonocarboxílico/farmacologia , Hormônio Liberador de Tireotropina/análogos & derivados , Hormônio Liberador de Tireotropina/farmacologia , Animais , Antiulcerosos/farmacologia , Atropina/farmacologia , Ácido Clorídrico/farmacologia , Injeções Intraventriculares , Masculino , Antagonistas Muscarínicos/farmacologia , Omeprazol/farmacologia , Permeabilidade/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Úlcera Gástrica/induzido quimicamente , VagotomiaRESUMO
PURPOSE: Pharmacokinetic studies of antibacterial agents for infectious eye diseases have usually been performed on normal rabbit eyes. In this study, the intraocular penetration of fluoroquinolone ophthalmic solutions was determined in normal rabbit eyes and in rabbit eyes that had the corneal epithelium intentionally removed. METHODS: We determined the intraocular penetration of ofloxacin (OFLX), levofloxacin (LVFX), and norfloxacin (NFLX), fluoroquinolone ophthalmic solutions that are already on the market and undergoing clinical studies, by injecting 50 microl of each solution into the cul-de-sacs of rabbit eyes three times at 15-min intervals. The drug concentration at 10, 30, 60, 120, and 240 min after final instillation was determined by high-performance liquid chromatography. RESULTS: The maximum concentration in the aqueous humor of normal rabbit eyes was 2.09 +/- 1.56 microg/ml (60 min, OFLX), 2.57 +/- 1.00 microg/ml (30 min, LVFX), and 0.42 +/- 0.12 microg/ml (120 min, NFLX). The drug concentration in the aqueous humor of eyes with intentionally removed corneal epithelium was 12.50 +/- 5.62 microg/ml (30 min, OFLX), 9.02 +/- 2.45 microg/ml (60 min, LVFX), and 8.54 +/- 5.17 microg/ml (30 min, NFLX). The drug penetration of the eye drops into eyes with removed corneal epithelium was around 6 times (OFLX), 3.5 times (LVFX), and 20 times (NFLX) higher than the penetration into the eye with normal cornea. CONCLUSION: Among the pharmacokinetic parameters of the three ophthalmic solutions according to the one-compartment model, the maximum concentration in the aqueous and the area under the concentration-time curve in the aqueous tended to be higher in the eyes with intentionally removed corneal epithelia than in those with normal corneas.
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Anti-Infecciosos/farmacocinética , Humor Aquoso/metabolismo , Córnea/metabolismo , Epitélio Corneano/fisiologia , Fluoroquinolonas/farmacocinética , Animais , Área Sob a Curva , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Levofloxacino , Masculino , Norfloxacino/farmacocinética , Ofloxacino/farmacocinética , Soluções Oftálmicas/farmacocinética , CoelhosRESUMO
BACKGROUND: Partial left ventriculectomy (PLV) helps some patients but is deleterious in others. Selection of patients who will benefit from PLV, and exclusion of those who will not is necessary for safe and effective application of the procedure. METHODS: Sixty-nine consecutive patients who underwent PLV were monitored with pressure-volume relationship analyses, Doppler echocardiography, and histopathologic studies of excised myocardium. These parameters were correlated with postoperative stroke volume (SV, ml), cardiac output (CO, L/min), ventricular function (improved, no change, or deteriorated), and postoperative course (duration of survival and/or hospital discharge). RESULTS: Positive responders (n = 36) with increased SV at reduced end diastolic pressure had significantly larger preoperative end-systolic dimension, smaller SV, and less stroke work with milder fibrosis than non- or negative responders (n = 33). In multivariate analyses, poor preoperative hemodynamics were associated with increased SV and CO, but these improvements did not lead to improved survival. Postoperative survival was negatively affected by larger preoperative left ventricular end-diastolic volume and larger excised-muscle-weight. Milder fibrosis and thicker excised wall were consistently related to improved ventricular function and survival. CONCLUSION: Although effects of PLV are related to preoperative status, factors affecting postoperative ventricular function and survival were often discordant. While poor preoperative ventricular function was associated with functional improvement without survival benefit, milder fibrosis, thicker excised wall and less myocardial resection were positive contributors to improved ventricular function, discharge, and survival. Preoperative evaluation with more cases and variables are needed to identify patients more likely to benefit from PLV.
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Procedimentos Cirúrgicos Cardíacos/métodos , Insuficiência Cardíaca/cirurgia , Disfunção Ventricular Esquerda/cirurgia , Adulto , Idoso , Pressão Sanguínea/fisiologia , Débito Cardíaco/fisiologia , Fibrose Endomiocárdica/fisiopatologia , Feminino , Insuficiência Cardíaca/fisiopatologia , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Miocárdio/patologia , Tamanho do Órgão , Volume Sistólico/fisiologia , Análise de Sobrevida , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
We describe a case of biliary cystadenocarcinoma that showed a longterm clinical course. A 69-year-old Japanese man was admitted to our hospital because of abdominal discomfort. The patient had been diagnosed with benign cystadenoma of the liver at another hospital in 1987 and had been followed up for 10 years. Abdominal ultrasonography (US) and computed tomography (CT) scan demonstrated a unilocular cystic lesion, which included multiple conspicuous papillary protrusions in the left hepatic lobe. Left lateral segmentectomy was performed, and intraoperative cholangiography revealed a communication between the cystic tumor and intrahepatic bile duct. The tumor contained clear mucinous fluid and enfolded multiple yellowish papillary projections on the cystic wall. Histological examination showed the tumor to be biliary cystadenocarcinoma. The patient is doing well 4 years after the operation.