RESUMO
Inflammatory pseudotumor (IPT) of the liver is a rare benign lesion of unknown etiology and is often accompanied by fever. Unexplained persistent fever unresponsive to antibiotics developed in a 70-year-old man suffering from intractable recurrent gouty arthritis. 67Ga-scintigraphy disclosed intense focal uptake in the upper abdomen. The lesion in the left lobe of the liver was an ill-defined hypodensity mass on computed tomographic scan and was enhanced on dynamic magnetic resonance imaging. The tumor was surgically removed and a diagnosis of IPT was made. Fever and arthritis resolved completely after surgery. Possible interaction between IPT of the liver and gouty arthritis was suggested.
Assuntos
Artrite Gotosa/complicações , Granuloma de Células Plasmáticas/complicações , Idoso , Artrite Gotosa/diagnóstico , Granuloma de Células Plasmáticas/diagnóstico , Humanos , Masculino , RecidivaRESUMO
The complete nucleotide sequence of pKDSC50, a large virulence plasmid from Salmonella enterica serovar Choleraesuis strain RF-1, has been determined. We identified 48 of the open reading frames (ORFs) encoded by the 49,503-bp molecule. pKDSC50 encodes a known virulence-associated operon, the spv operon, which is composed of genes essential for systemic infection by nontyphoidal Salmonella. Analysis of the genetic organization of pKDSC50 suggests that the plasmid is composed of several virulence-associated genes, which include the spvRABCD genes, plasmid replication and maintenance genes, and one insertion sequence element. A second virulence-associated region including the pef (plasmid-encoded fimbria) operon and rck (resistance to complement killing) gene, which has been identified on the virulence plasmid of S. enterica serovar Typhimurium, was absent. Two different replicon regions, similar to the RepFIIA and RepFIB replicons, were found. Both showed high similarity to those of the pO157 plasmid of enterohemorrhagic Escherichia coli O157:H7 and the enteropathogenic E. coli (EPEC) adherence factor plasmid harbored by EPEC strain B171 (O111:NM), as well as the virulence plasmids of Salmonella serovars Typhimurium and Enteritidis. Comparative analysis of the nucleotide sequences of the 50-kb virulence plasmid of serovar Choleraesuis and the 94-kb virulence plasmid of serovar Typhimurium revealed that 47 out of 48 ORFs of the virulence plasmid of serovar Choleraesuis are highly homologous to the corresponding ORFs of the virulence plasmid of serovar Typhimurium, suggesting a common ancestry.
Assuntos
DNA Bacteriano/química , Plasmídeos , Salmonella enterica/genética , Sequência de Bases , Conjugação Genética , Elementos de DNA Transponíveis , Fases de Leitura Aberta , Salmonella enterica/crescimento & desenvolvimento , Salmonella enterica/patogenicidade , VirulênciaRESUMO
Bisphenol A (BPA) and nonylphenol (NP) were treated with manganese peroxidase (MnP) and laccase prepared from the culture of lignin-degrading fungi. Laccase in the presence of 1-hydroxybenzotriazole (HBT), the so-called laccase-mediator system, was also applied to remove the estrogenic activity. Both chemicals disappeared in the reaction mixture within a 1-h treatment with MnP but the estrogenic activities of BPA and NP still remained 40% and 60% in the reaction mixtures after a 1-h and a 3-h treatment, respectively. Extension of the treatment time to 12 h completed the removal of estrogenic activities of BPA and NP. The laccase has less ability to remove these activities than MnP, but the laccase-HBT system was able to remove the activities in 6 h. A gel permeation chromatography (GPC) analysis revealed that main reaction products of BPA and NP may be oligomers formed by the action of enzymes. Enzymatic treatments extended to 48 h did not regenerate the estrogenic activities, suggesting that the ligninolytic enzymes are effective for the removal of the estrogenic activities of BPA and NP.
Assuntos
Basidiomycota/enzimologia , Enzimas/metabolismo , Estrogênios não Esteroides/metabolismo , Fenóis/metabolismo , Compostos Benzidrílicos , Biodegradação Ambiental , Lacase , Lignina/metabolismo , Oxirredução , Oxirredutases/genética , Oxirredutases/metabolismo , Peroxidases/genética , Peroxidases/metabolismo , Técnicas do Sistema de Duplo-HíbridoRESUMO
The present study was designed to evaluate the effects of an ACE inhibitor, lisinopril, and a calcium antagonist, nitrendipine, on urinary albumin excretion (UAE) and renal function in mild to moderate essential hypertensive patients with microalbuminuria. After the 4-week drug-free period, 17 patients were randomly divided into two groups. The first group (group 1: n=8) received lisinopril 10-20 mg daily for 8 weeks followed by nitrendipine 5-10 mg daily for another 8 weeks. The second group (group 2: n=9) received nitrendipine 5-10 mg daily for 8 weeks followed by lisinopril 10-20 mg daily for another 8 weeks. The mean blood pressure (MBP) significantly decreased in a similar manner in both groups. UAE significantly decreased after 8 weeks of treatment with lisinopril in group 1 and after 8 weeks of subsequent treatment with lisinopril in group 2. On the other hand, UAE was not altered by treatment with nitrendipine. The changes in UAE were significantly correlated with changes in MBP after 8 weeks of treatment with nitrendipine, but not after 8 weeks of treatment with lisinopril. No significant changes in creatinine clearance, urinary excretion of sodium or urinary N-acetyl-beta-D-glucosaminide were observed by any treatment in either group. These results suggest that lisinopril, not nitrendipine, reduces UAE in essential hypertensive patients with microalbuminuria independently of its effective antihypertensive properties.
Assuntos
Albuminúria/urina , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Hipertensão/fisiopatologia , Hipertensão/urina , Rim/fisiopatologia , Lisinopril/uso terapêutico , Nitrendipino/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Feminino , Humanos , Rim/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
The present study was undertaken to clarify whether celiprolol and atenolol, beta1-selective beta blockers with and without intrinsic sympathomimetic activity (ISA), respectively, might improve ischemic damage in the isolated perfused hearts of spontaneously hypertensive rats (SHR), and whether long-term treatment with celiprolol may reduce left ventricular hypertrophy (LVH) in patients with essential hypertension. Atenolol (50 mg/kg/day) or celiprolol (300 mg/kg/day) for 7 weeks significantly reduced the blood pressure in SHR to the same degree, and both drugs decreased the heart rate, but the magnitude of the fall in heart rate was significantly higher with atenolol treatment than with celiprolol treatment. Both treatments significantly reduced the ratio of LV weight to body weight in SHR and significantly improved the coronary reserve in SHR to the same extent. Both treatments significantly improved the extent of recovery of the pressure-rate product and the extent of percent recovery of the coronary flow after reperfusion following 30 min of ischemia in SHR. Celiprolol treatment in patients with essential hypertension for 12 months significantly decreased interventricular septal thickness (IVST)+LV posterior wall thickness (PWT) and LV mass index (LVMI), but there was no significant correlation between IVST+PWT or LVMI and blood pressure before and after treatment. IVST+PWT and LVMI were significantly decreased after 3 months of treatment and these LVH indices were significantly smaller after 6 and 12 months of treatment than after 3 months of treatment. In conclusion, both celiprolol and atenolol treatment reduced LVH and improved the ischemic damage in SHR. In essential hypertensive patients with LVH, celiprolol treatment effectively reduced blood pressure and achieved LVH regression.
Assuntos
Anti-Hipertensivos/administração & dosagem , Celiprolol/administração & dosagem , Hipertensão/tratamento farmacológico , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Antagonistas Adrenérgicos beta/administração & dosagem , Adulto , Animais , Atenolol/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Circulação Coronária/efeitos dos fármacos , Feminino , Teste de Tolerância a Glucose , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/complicações , Hipertrofia Ventricular Esquerda/complicações , Hipertrofia Ventricular Esquerda/patologia , Lipídeos/sangue , Masculino , Miocárdio/patologia , Tamanho do Órgão/efeitos dos fármacos , Perfusão , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKYRESUMO
Microsurgical reconstruction after total glossectomy can greatly improve quality of life; however, postoperative functional results are often unstable, and the effectiveness of total glossectomy remains questionable. To determine the problems of reconstruction after total glossectomy with laryngeal preservation and to examine the functional results of swallowing and speech, 30 patients who had undergone total glossectomy and reconstruction with free flaps were reviewed for this study. The patients ranged in age from 20 to 73 years, and 23 of the 30 had undergone reconstruction with a rectus abdominis musculocutaneous flap. Wider and thicker flaps were designed and transferred and were sutured to suspend the larynx. To maintain physiologic swallowing function after surgery, the extent of laryngeal suspension and cricopharyngeal myotomy was limited. Of the 30 patients, 21 (70 percent) could be decannulated with laryngeal preservation; 20 of these 21 could tolerate a normal/soft/pureed diet, and 1 was limited to a fluid diet. Speech was intelligible in 16 of the 19 patients evaluated. In 9 of the 30 patients, laryngeal function could not be preserved. In four of these nine patients, additional resection combined with total glossectomy caused severe aspiration and recurrent pneumonia. Two patients with preoperative cerebral dysfunction were also poor candidates for laryngeal preservation. Additionally, the transferred flap's lack of bulk in the oral cavity and the advanced age (73 years) of one patient and the poor motivation of another may have contributed to postoperative aspiration. Aspiration occurred in one patient because of local recurrence of a tumor. The presence of preoperative cerebral dysfunction (p = 0.025), resection of the epiglottis (p = 0.005), and postoperative orocutaneous fistulas (p = 0.04) were significantly associated with the failure of laryngeal preservation. However, because of the difficulty of enrolling a sufficient number of patients in the study and the inherent limitations of retrospective studies, multivariate analysis in this study showed that no factors, such as patient age, flap volume, and the type of neck dissection, were significant predictors of laryngeal preservation. Although prospective studies are necessary, the function of individual patients must be assessed so that the study experiences discussed here can be applied to subsequent patients.
Assuntos
Glossectomia/reabilitação , Complicações Pós-Operatórias , Retalhos Cirúrgicos , Adulto , Idoso , Ingestão de Alimentos , Feminino , Humanos , Laringe/cirurgia , Masculino , Microcirurgia/efeitos adversos , Pessoa de Meia-Idade , Boca/cirurgia , Esvaziamento Cervical , Estudos Retrospectivos , Fala , Retalhos Cirúrgicos/efeitos adversos , Neoplasias da Língua/cirurgiaRESUMO
A 74-year-old male was affected concurrently with squamous cell carcinoma of the left eyelid and adenocarcinoma of the colon, both with lymph node metastasis. He underwent exenteration of the left orbit with left modified radical neck dissection and subsequently resection of the transverse colon with regional lymph node dissection. The patient has been treated by an adoptive immunotherapy as a sole postoperative modality without receiving any chemotherapeutic agents causing immunosuppression. For the adoptive immunotherapy, autologous peripheral blood lymphocytes were activated with an immobilized anti-CD3 antibody and IL-2 for 14 days (the CD3-AT cells). The infusion with 1.38 x 10(10) CD3-AT cells has been repeated 150 times in total at the time of writing. Neither recurrence nor additional metastasis has been detected for 6 years after surgery.
Assuntos
Adenocarcinoma/terapia , Carcinoma de Células Escamosas/terapia , Neoplasias do Colo/terapia , Neoplasias Palpebrais/terapia , Imunoterapia Adotiva , Linfonodos/patologia , Neoplasias Primárias Múltiplas , Adenocarcinoma/imunologia , Adenocarcinoma/secundário , Idoso , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/secundário , Neoplasias do Colo/imunologia , Neoplasias do Colo/patologia , Intervalo Livre de Doença , Neoplasias Palpebrais/imunologia , Neoplasias Palpebrais/patologia , Humanos , Metástase Linfática , Ativação Linfocitária , Masculino , Muromonab-CD3/imunologia , Esvaziamento Cervical , Cuidados Pós-OperatóriosRESUMO
Primary cultures of neonatal cardiac myocytes were used to determine both the identity of second messengers that are involved in vasopressin receptor-mediated effects on cardiac hypertrophy and the type of vasopressin receptor that is involved in vasopressin-induced cell growth. Neonatal rat myocytes were plated at a density of 1x10(6) cells per 60 mm dish and were incubated with serum-free medium for 7 days. Treatment of myocytes with vasopressin significantly increased the RNA-to-DNA ratio, by 18-25%, at culture days 4-6 and the protein-to-DNA ratio by 18-20% at culture days 5-7. Rates of protein synthesis were determined to assess their contribution to protein contents during myocyte growth. Vasopressin significantly accelerated rates of protein synthesis by 25% at culture day 6. Intracellular free Ca(2+) ([Ca(2+)](i)) was transiently increased after vasopressin exposure. After the peak increase in [Ca(2+)](i) at less than 30 s, there was a sustained increase for at least 5 min. The specific activity of protein kinase C in the particulate fraction was increased rapidly after exposure to vasopressin, and its activity remained higher for 30 min, returning to its control level within 60 min. The activity of protein kinase C in the cytosol was significantly decreased at all times after exposure to vasopressin. After vasopressin treatment, the content of c-fos mRNA was increased. The stimulatory effects of vasopressin on these parameters were significantly inhibited by vasopressin V(1A) receptor antagonist, OPC-21268, but not by vasopressin V(2) receptor antagonist, OPC-31260. These results suggest that vasopressin directly induces myocyte hypertrophic growth via the V(1A) receptor in neonatal rat heart cells.
Assuntos
Animais Recém-Nascidos/fisiologia , Cardiomegalia/patologia , Miocárdio/patologia , Receptores de Vasopressinas/fisiologia , Animais , Antagonistas dos Receptores de Hormônios Antidiuréticos , Benzazepinas/farmacologia , Northern Blotting , Cálcio/metabolismo , Cardiomegalia/enzimologia , Cardiomegalia/metabolismo , Células Cultivadas , Meios de Cultura , DNA/biossíntese , Cinética , Miocárdio/enzimologia , Miocárdio/metabolismo , Piperidinas/farmacologia , Biossíntese de Proteínas , Proteína Quinase C/metabolismo , Proteínas/metabolismo , Proteínas Proto-Oncogênicas c-fos/biossíntese , Quinolonas/farmacologia , RNA Mensageiro/biossíntese , Ratos , Ratos Sprague-Dawley , Sistemas do Segundo Mensageiro/efeitos dos fármacos , Sistemas do Segundo Mensageiro/fisiologia , Vasopressinas/farmacologiaAssuntos
Hipertensão/etiologia , Hipertensão/terapia , Idoso , Anti-Hipertensivos/uso terapêutico , Ritmo Circadiano , Feminino , Hemodinâmica , Humanos , Hipertensão/fisiopatologia , Nefropatias/complicações , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/complicações , Insuficiência Respiratória/complicaçõesRESUMO
Thirteen patients who had undergone ablative surgery for advanced squamous cell carcinoma in which more than half of the tongue had been resected underwent reconstruction in which the cutaneous nerve of a free flap was anastomosed to the stump of the transected lingual nerve. Eight of the patients underwent reconstruction with an innervated anterolateral thigh flap and five patients underwent reconstruction with an innervated rectus abdominis musculocutaneous flap. Sensory recovery of the flap at least 6 months postoperatively was compared in these 13 patients and in 16 additional patients who received noninnervated versions of the same flaps for the same defect. The degree of sensory recovery of innervated thigh flaps was significantly greater than that of noninnervated ones in all modalities and that of innervated rectus abdominis flaps was also greater than that of noninnervated flaps, except for hot and cold perception. These results indicate that sensory regrowth occurs in most areas through the surgically created pathways. However, results of Semmes-Weinstein testing showed that recovery did not reach the level of protective sensation in either type of innervated flap. Although these findings must be followed by additional objective and functional tests and the need for sensory reeducation should be considered, this simple operative procedure can improve postoperative intraoral function and should be attempted whenever possible after ablative surgery.
Assuntos
Boca/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos/inervação , Músculos Abdominais , Adulto , Idoso , Carcinoma de Células Escamosas/cirurgia , Glossectomia , Humanos , Pessoa de Meia-Idade , Neoplasias Bucais/cirurgia , Sensação , Coxa da PernaRESUMO
Angiotensin II activates p21ras, and mediates cardiac hypertrophic growth through the type 1 angiotensin II receptor in cardiac myocytes. An inhibitor of 3-hydroxy-3-methyglutaryl-coenzyme A (HMG-CoA) reductase has been shown to block the post-translational farnesylation of p21ras and inhibit protein synthesis in several cell types. Primary cultures of neonatal cardiac myocytes were used to determine whether HMG-CoA reductase inhibitors, lovastatin, simvastatin and pravastatin inhibit the angiotensin II-induced hypertrophic growth. Angiotensin II (10(-6) M) significantly increased protein-DNA ratio, RNA-DNA ratio, ratios of protein synthesis and mitogen-activated protein (MAP) kinase activity. Lipid-soluble HMG-CoA reductase inhibitors, lovastatin (10(-6) M) and simvastatin (10(-6) M) partially and significantly inhibited the angiotensin II-induced increases in these parameters, but a water-soluble HMG-CoA reductase inhibitor, pravastatin (10(-6) M) did not. Mevalonate (10(-4) M) overcame the inhibitory effects of lovastatin and simvastatin on angiotensin II-induced increases in these parameters. A selective protein kinase C inhibitor, calphostin C (10(-6) M) partially and significantly prevented angiotensin II-induced increases in these parameters, and treatment with both lovastatin and calphostin C inhibited completely. Angiotensin II increased p21ras activity and membrane association, and lovastatin inhibited them. These studies demonstrate that a lipid-soluble HMG-CoA reductase inhibitor, lovastatin, may prevent angiotensin II-induced cardiac hypertrophy, at least in part, through p21ras/MAP kinase pathway, which is linked to mevalonate metabolism.
Assuntos
Angiotensina II/fisiologia , Cardiomegalia/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Lovastatina/farmacologia , Angiotensina II/farmacologia , Animais , Animais Recém-Nascidos , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Cardiomegalia/patologia , Divisão Celular/efeitos dos fármacos , Membrana Celular/fisiologia , Células Cultivadas , DNA/biossíntese , Miocárdio/patologia , Naftalenos/farmacologia , Pravastatina/farmacologia , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/fisiologia , RNA/biossíntese , Ratos , Ratos Sprague-Dawley , Sinvastatina/farmacologiaRESUMO
Arginine vasopressin (AVP) is known to contribute significantly to the pathogenesis of congestive heart failure and hypertension. However, little is known about its effect on the myocardium. The present study was conducted to determine whether AVP directly increases the rate of protein synthesis in isolated, perfused rat heart, and, if so, the mechanism involved. Elevation of the aortic pressure from 60 to 120 mmHg in perfused rat heart accelerated the rate of protein synthesis which was associated with increases in cAMP levels and Ca2+ uptake. AVP (100 microM) increased Ca2+ uptake and accelerated the rate of protein synthesis without a change in cAMP concentration. The latter events were inhibited by OPC-21268 (100 microM), a selective V1 receptor antagonist, or amiloride (100 microM), an inhibitor of the Na+/H+ exchange system. However, increases in cAMP concentrations, Ca2+ uptake, and rates of protein synthesis associated with the elevated aortic pressure were not inhibited by amiloride. Thus, AVP directly increased the rate of protein synthesis via the V1 receptor that is sensitive to amiloride, a mechanism that differs from the cAMP-dependent mechanism that is responsible for the cardiac hypertrophy induced by pressure overload.
Assuntos
Arginina Vasopressina/farmacologia , Miocárdio/metabolismo , Biossíntese Peptídica/efeitos dos fármacos , Perfusão , Receptores de Vasopressinas/metabolismo , Amilorida/farmacologia , Animais , Antagonistas dos Receptores de Hormônios Antidiuréticos , Cálcio/metabolismo , AMP Cíclico/metabolismo , Técnicas In Vitro , Masculino , Piperidinas/farmacologia , Pressão/efeitos adversos , Quinolonas/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
We successfully fabricated a large maxillofacial prosthesis for replacement of a total mandibular defect resulting from surgical failure to reconstruct the mandible. Although a number of reports have described procedures for fabricating midfacial prostheses, there is little information on prostheses to compensate for total loss of the mandible. A 54-year-old woman was referred to the Dentistry and Oral Surgery Division of the National Cancer Center Hospital with total loss of the mandible and the surrounding facial soft tissue. The facial prosthesis we used to treat this patient is unique in that it is adequately retained without the use of extraoral implants and conventional adhesives. This prosthesis is retained by the bilateral auricles and the remaining upper front teeth. We present details of the design of this large silicone maxillofacial prosthesis, with which we successfully rehabilitated the patient.
Assuntos
Mandíbula/cirurgia , Doenças Mandibulares/cirurgia , Implante de Prótese Maxilofacial/métodos , Prótese Maxilofacial , Osteorradionecrose/cirurgia , Procedimentos de Cirurgia Plástica , Feminino , Humanos , Doenças Mandibulares/etiologia , Pessoa de Meia-Idade , Osteorradionecrose/etiologia , Neoplasias da Língua/radioterapia , Neoplasias da Língua/cirurgiaRESUMO
BACKGROUND: Production of heat shock protein 70 (HSP70) in the heart is induced by hemodynamic stress, but its intracellular signal transduction system has not been elucidated well. OBJECTIVE: To investigate the hypothesis that protein kinase A (PKA)-dependent and protein kinase C (PKC)dependent systems are involved in the pressure-induced expression of HSP70 mRNA in perfused adult rat heart METHODS: Isolated tetrodotoxin-arrested Sprague-Dawley rat hearts were perfused as Langendorff preparations at a constant aortic pressure of 60 mmHg. Aortic pressure in rats of the pressure-overloaded group was elevated from 60 to 120 mmHg for 2-120 min. cAMP contents and rates of synthesis of protein were measured by radioimmunoassay and the incorporation of [14C]-phenylalanine into total heart protein, respectively. Expression of HSP70 mRNA was determined by Northern blot analysis. RESULTS: Elevation of aortic pressure significantly increased cAMP content after 2 min of perfusion (by 41%), significantly increased rates of synthesis of protein during the second hour of perfusion (by 41%), and induced expression of HSP70 mRNA maximally after 60 min of perfusion (2.7-fold the control value). Exposure to glucagon, forskolin or 1 -methyl-3-isobutylxanthine mimicked increases in these parameters caused by elevation of aortic pressure. Administration of a selective PKA inhibitor, H-89, significantly prevented induction of increases in expression of HSP70 mRNA and rates of synthesis of protein by a high pressure overload and exposure to agents that increase cAMP content. Furthermore, administration of phorbol ester induced expression of HSP70 mRNA. Administration of a PKC inhibitor, calphostin C, significantly prevented induction of increases in expression of HSP70 mRNA by a pressure overload and by exposure to phorbol ester. CONCLUSIONS: These results suggest that the pressure-induced induction of production of HSP70 is regulated both by PKA-dependent and by PKC-dependent systems during periods of active synthesis of protein in adult rat heart.
Assuntos
Pressão Sanguínea/genética , Pressão Sanguínea/fisiologia , Proteínas Quinases Dependentes de AMP Cíclico/fisiologia , Proteínas de Choque Térmico HSP70/genética , Miocárdio/metabolismo , Proteína Quinase C/fisiologia , RNA Mensageiro/genética , Sulfonamidas , 1-Metil-3-Isobutilxantina/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Cardiomegalia/etiologia , Cardiomegalia/genética , Cardiomegalia/fisiopatologia , Colforsina/farmacologia , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Expressão Gênica/efeitos dos fármacos , Glucagon/farmacologia , Hipertensão/genética , Hipertensão/fisiopatologia , Técnicas In Vitro , Isoquinolinas/farmacologia , Masculino , Naftalenos/farmacologia , Perfusão , Biossíntese de Proteínas , Proteína Quinase C/antagonistas & inibidores , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de SinaisRESUMO
It is not certain whether activation of the Ras/mitogen-activated protein (MAP) kinase pathway is involved in cardiac hypertrophy. 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, such as lovastatin, prevent farnesylation of the Ras protein, which is critical for Ras's membrane localization and function. Therefore, the present study was undertaken to investigate the role of the Ras pathway, which is linked to mevalonate metabolism, in the mechanism of stretch-induced myocyte hypertrophy. Myocytes isolated from 1- to 2-day-old rats were cultured at 4.1 x 10(6) cells per well in a deformable silicon dish and incubated with serum-free medium for 7 days. The cultures were stretched by 15% on culture day 4. Stretch increased the RNA/DNA ratio by 20% to 26% on culture days 5 and 6 and the protein/DNA ratio by 18% to 20% on culture days 6 and 7. Stretch accelerated rates of protein synthesis by 24% on culture day 6. Stretch increased protein kinase C (PKC) activity, MAP kinase activity, and c-fos mRNA expression. A selective PKC inhibitor, calphostin C (1 x 10(-6) M), prevented the stretch-induced increase in PKC activity, but lovastatin (7.5 x 10(-6) M) did not. Lovastatin as well as calphostin C partially but significantly inhibited the stretch-induced increases in MAP kinase activity, c-fos mRNA expression, and protein synthesis. Pretreatment with both lovastatin and calphostin C completely inhibited the increases in these variables caused by stretch. Lovastatin as well as calphostin C prevents stretch-induced cardiac hypertrophy. These results suggest that mechanical stretch may activate the Ras pathway, which is linked to mevalonate metabolism, in cultured neonatal rat heart cells.
Assuntos
Coração/fisiologia , Ácido Mevalônico/metabolismo , Miocárdio/metabolismo , Animais , Animais Recém-Nascidos , Células Cultivadas , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Coração/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hipertrofia/induzido quimicamente , Hipertrofia/fisiopatologia , Lovastatina/farmacologia , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Miocárdio/citologia , Miocárdio/patologia , Naftalenos/farmacologia , Estimulação Física , Biossíntese de Proteínas , Proteína Quinase C/antagonistas & inibidores , Proteínas/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/genética , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia , Estresse MecânicoRESUMO
OBJECTIVE: To report on a new concept and simple operative procedure to conform the diameter of the oral end of free jejunal grafts to that of pharyngeal defects for reconstruction of the lower pharyngeal space. DESIGN AND METHODS: A preliminary study showed that the jejunum is supplied by a highly vascular network and that longitudinal paramesenteric incisions can be made without disturbing the blood supply of the jejunum. We then developed the following operative procedure. The position of the highest point of the pharyngeal defect and the site of the recipient vessels are determined. The free jejunal graft is positioned with its mesentery in correspondence with the location of the recipient vessels. The position of a longitudinal incision 180 degrees to the highest point of the defect is then determined. After the oral border of the jejunum is opened with scissors, a pharyngojejunal end-to-end anastomosis is performed. PATIENTS: Eighteen patients with defects of the lower pharyngeal space after cancer treatment. RESULTS: We transferred jejunal grafts in 18 patients using this operative procedure. In 7 of these patients, paramesenteric incisions were made. The lengths of the incisions ranged from 2 to 8 cm. Transfer was successful in all 18 patients. Postoperative leakage occurred in 1 patient in whom an antimesenteric incision had been made; however, a fistula did not develop. CONCLUSIONS: Our method allows defects of the lower pharyngeal space to be reconstructed with end-to-end anastomosis of free jejunal grafts regardless of the location of the defect or of recipient vessels. This method is simple and appropriate for correcting large pharyngeal defects.
Assuntos
Jejuno/transplante , Faringe/cirurgia , Adulto , Idoso , Anastomose Cirúrgica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Faringe/fisiopatologia , Procedimentos de Cirurgia PlásticaRESUMO
The present study investigated the effect of bisoprolol, a beta 1-selective beta-blocker without intrinsic sympathomimetic activity (ISA), on lipid and glucose metabolism and quality of life (QOL) in elderly patients with essential hypertention. Bisoprolol at doses of 5-10 mg was administered once daily for 12 weeks to 60 non-elderly and 21 elderly outpatients with mild to moderate essential hypertension. In both groups bisoprolol significantly decreased both systolic and diastolic blood pressures and significantly reduced pulse rates to the same extent. The levels of serum cholesterol, HDL-cholesterol and triglyceride, and the response of plasma glucose and insulin to 75 g oral glucose load, were not changed in either group by the bisoprolol treatment. Bisoprolol significantly improved QOL in both groups. Bradycardia, a side effect attributable to bisoprolol, was noted in only one patient in the elderly group. These results suggest that bisoprolol is a safe and useful antihypertensive drug in elderly and non-elderly patients with essential hypertension.