RESUMEN
OBJECTIVE: Long-term survival of patients with neonatal-onset carbamoyl-phosphate synthetase 1 deficiency (CPS1D), an autosomal recessive disorder characterized by repeated, life-threatening hyperammonemia, is rare. We describe the diagnosis and clinical management of a teenager with neonatal-onset CPS1D who did not undergo therapeutic liver transplantation. CASE REPORT: Following emergent neonatal therapy, the patient was diagnosed with CPS1D based on clinical, radiological, biochemical and genetic analyses. Her clinical course, neurobehavioral development and therapeutic interventions are presented and discussed. RESULTS: Born from nonconsanguineous parents, the proband underwent phototherapy for neonatal jaundice, associated with acute encephalopathy, apnea and cerebral edema. Based on blood and urinary biochemical abnormalities, neonatal-onset CPS1D was diagnosed. Her hyperammonemia was corrected by hemodialysis, followed by sodium benzoate, L-arginine, levocarnitine and protein-free diet therapy. Because of a relapse and persistent neurobehavioral regression by age 1, a planned liver transplantation was cancelled. At age 10, sodium phenylbutyrate was substituted as ammonia scavenger. Genetic testing revealed compound heterozygote c.2359C>T (R787X) and c.236+6T>C variants of CPS1, confirming her diagnosis. Despite severe neurological sequelae, the patient is 16 and in stable condition. CONCLUSIONS: Our case suggests that early hemodialysis and pharmacologic interventions for acute neonatal hyperammonemia can improve the prognosis of patients with neonatal-onset CPS1D.
Asunto(s)
Arginina/uso terapéutico , Encefalopatías Metabólicas/terapia , Enfermedad por Deficiencia de Carbamoil-Fosfato Sintasa I/terapia , Carnitina/uso terapéutico , Hiperamonemia/terapia , Fenilbutiratos/uso terapéutico , Diálisis Renal , Benzoato de Sodio/uso terapéutico , Femenino , Humanos , Recién NacidoRESUMEN
The purpose of this study was to evaluate the stability and viability of mandibular bone regeneration using a poly(L-lactide) (PLLA) mesh and autogenous particulate cancellous bone and marrow (PCBM). Sixty-two procedures were undertaken at eight hospitals (22 malignant tumours, 30 benign tumours, five cysts, two osteomyelitis, two trauma, and one atrophy of the alveolar ridge); the success rate was 84%. The follow-up period was between 9 and 200 months (mean 88.2 months). Consequently, bone regeneration at 6 months postoperation was excellent in 35 cases (57%), good in 17 cases (27%), and poor in 10 cases (16%). In six of the 'poor' cases, the PLLA mesh was removed due to local infection early after surgery. Bone resorption>20% was observed in only one of 46 cases with a follow-up term of >1 year. There were no signs of any other adverse effects except in one case where a section of the tray broke off late in the follow-up period. It is concluded that this method is stable and effective due to favourable morphological and functional recovery and low invasiveness. It may thus be a useful alternative procedure for mandibular reconstruction.
Asunto(s)
Implantes Absorbibles , Autoinjertos/trasplante , Trasplante de Médula Ósea/métodos , Trasplante Óseo/métodos , Reconstrucción Mandibular/métodos , Poliésteres/química , Mallas Quirúrgicas , Adolescente , Adulto , Anciano , Aumento de la Cresta Alveolar/métodos , Regeneración Ósea/fisiología , Resorción Ósea/etiología , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Enfermedades Mandibulares/cirugía , Traumatismos Mandibulares/cirugía , Neoplasias Mandibulares/cirugía , Reconstrucción Mandibular/instrumentación , Persona de Mediana Edad , Quistes Odontogénicos/cirugía , Osteomielitis/cirugía , Complicaciones Posoperatorias , Estudios Prospectivos , Andamios del Tejido , Resultado del Tratamiento , Adulto JovenRESUMEN
WHAT IS KNOWN AND OBJECTIVE: Calcium channel blockers (CCBs), which have been widely used for the treatment of hypertension and angina pectoris, decrease lower oesophageal sphincter pressure and, as a result, can exacerbate gastrointestinal disease. In a previous study, increased risk of exacerbation of gastrointestinal disease among elderly patients following treatment with CCBs was identified. The prevalence of gastrointestinal diseases has increased in elderly patients, and it is possible that treatment with CCBs may have undesirably influenced this increase. The change in risk of gastrointestinal disease can be estimated by analysing changes in the prescription of antisecretory drugs as an outcome of exacerbation of gastrointestinal disease caused by CCBs. METHODS: It was hypothesized that patients who were prescribed CCBs would also change their use of antisecretory drugs. From September 2005 to August 2009, a dynamic retrospective cohort study was performed at five community pharmacies in Nagasaki, Japan, to assess alteration of antisecretory drug therapy following treatment with CCBs. Correlations with alterations of antisecretory drug therapy were determined by the Cox proportional hazards model. RESULTS AND DISCUSSION: The proposed study included 260 patients who were prescribed CCBs and 155 controls. During the study period, 53 patients were prescribed CCBs and 13 controls altered their antisecretory drug therapy; the hazard ratio was 2·22 (95% CI 1·25-4·26). WHAT IS NEW AND CONCLUSION: Calcium channel blocker treatment of patients with gastrointestinal disease was associated with alteration in frequency of prescription and an increase in dosage of antisecretory drugs. For clinical management of hypertension, alternative antihypertensive drugs may be considered for patients with gastrointestinal diseases. Further studies are required to determine the influence of CCB therapy on gastroesophageal diseases, suggested by the increase in use of antisecretory drugs.
Asunto(s)
Bloqueadores de los Canales de Calcio/efectos adversos , Fármacos Gastrointestinales/uso terapéutico , Enfermedades Gastrointestinales/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Bloqueadores de los Canales de Calcio/uso terapéutico , Estudios de Cohortes , Servicios Comunitarios de Farmacia/estadística & datos numéricos , Relación Dosis-Respuesta a Droga , Femenino , Fármacos Gastrointestinales/administración & dosificación , Enfermedades Gastrointestinales/fisiopatología , Humanos , Japón , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
BACKGROUND: The location of a parotid tumor affects the choice of surgery, and there is a risk of damaging the facial nerve during surgery. Thus, differentiation between superficial and deep lobe parotid tumors is important for appropriate surgical planning. PURPOSE: To evaluate the usefulness of using the parotid duct, in addition to the retromandibular vein, for differentiating between superficial and deep lobe parotid tumors on MR images. MATERIAL AND METHODS: Magnetic resonance images of 42 parotid tumors in 40 patients were reviewed to determine whether the tumor was located in the superficial or deep lobe. In each case, the retromandibular vein and the parotid duct were used to locate the tumor. The parotid duct was only used in cases where the tumor and the duct were visualized on the same image. RESULTS: Using the retromandibular vein criterion, 71% of deep lobe and 86% of superficial lobe tumors were correctly diagnosed, providing an accuracy of 81%. However, the accuracy achieved when using the parotid duct criterion was 100%, although it could be applied to only 28 of the 42 cases. Based on these results, we defined the following diagnostic method: the parotid duct criterion is first applied, and for cases in which it cannot be applied, the retromandibular vein criterion is used. The accuracy of this method was 88%, which was better than that achieved using the retromandibular vein criterion alone. CONCLUSION: The parotid duct criterion is useful for determining the location of parotid tumors. Combining the parotid duct criterion with the retromandibular vein criterion might improve the diagnostic accuracy of parotid tumor location compared to using the latter criterion alone.
Asunto(s)
Imagen por Resonancia Magnética/métodos , Glándula Parótida/patología , Neoplasias de la Parótida/patología , Adulto , Anciano , Medios de Contraste , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Glándula Parótida/cirugía , Neoplasias de la Parótida/cirugía , Estudios RetrospectivosRESUMEN
BACKGROUND AND OBJECTIVE: Calcium channel blockers (CCBs) have been widely used for the treatment of hypertension and angina pectoris. It is presumed that CCBs decrease the lower esophageal sphincter pressure and as a result, the risk of gastrointestinal disease may be increased. Since the prevalence of gastrointestinal diseases has increased in elderly patients, it is possible that treatment with CCBs may have contributed to this increase. Therefore, we considered that the risk of exacerbating gastrointestinal disease among elderly patients by CCBs can be estimated by using the prescription ratio of antisecretory drugs as an outcome. METHOD: We hypothesized that patients who are prescribed CCBs would increase the use of antisecretory drugs involving H(2)-receptor antagonists and proton pump inhibitors (PPIs). From January 2001 to December 2005, a dynamic retrospective cohort study was performed at three community pharmacies in Nagasaki city, Japan, to assess the use of antisecretory drugs following treatment with CCBs among elderly patients. The correlation of initiation of antisecretory drugs treatment to maintenance therapy with PPIs was determined by the Cox proportional hazards model. RESULTS: The proposed study includes 303 patients prescribed CCBs and 258 controls. During the study period, 138 patients prescribed CCBs and 66 controls were initiated by giving antisecretory drugs; the hazard ratio was 1.40 (95% confidence interval 1.21-1.63). Eighty two patients taking CCBs and 32 controls were initiated by the maintenance therapy with PPIs; the hazard ratio was 1.48 (95% confidence interval 1.21-1.83). CONCLUSION: Patients who simultaneously initiated the use of antisecretory drugs with CCBs could not be found. Therefore, antisecretory drugs have not been used to prevent the gastrointestinal diseases caused by CCBs. The results obtained in this study suggest that the risk of gastrointestinal disease could be increased by long-term treatment with CCBs for elderly patients.
Asunto(s)
Bloqueadores de los Canales de Calcio/efectos adversos , Enfermedades Gastrointestinales/etiología , Antagonistas de los Receptores H2 de la Histamina/uso terapéutico , Inhibidores de la Bomba de Protones/uso terapéutico , Anciano , Anciano de 80 o más Años , Bloqueadores de los Canales de Calcio/uso terapéutico , Estudios de Cohortes , Esfínter Esofágico Inferior/efectos de los fármacos , Esfínter Esofágico Inferior/metabolismo , Femenino , Enfermedades Gastrointestinales/epidemiología , Enfermedades Gastrointestinales/prevención & control , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
The involvement of bacterial translocation in small intestinal ischemia-reperfusion injuries and the efficacy of using anti-CINC antibodies for treatment were investigated. A model for ischemia-reperfusion injury of the small intestine was constructed by clamping the supramesenteric artery (for 90 min) in rats. Anti-CINC antibodies and saline were given just before the induction of ischemia in the treatment group and the control group, respectively. Six hours after reperfusion, bacteria were detected in the mesenteric lymph nodes, but the 'bacteria-positive' rate was significantly lower in the treatment group than in the control group. Bacterial cultures and endotoxins in the blood were negative in both groups up to 24 h later. The plasma cytokine levels showed similar variations, although the increases were significantly lower after reperfusion in the treatment group. In addition, the degrees of neutrophil infiltration and mucosal injury were attenuated in the small intestine, and the structure of the liver was maintained. Furthermore, the 1-week survival was improved. These results suggest that bacterial translocation occurred predominantly via the lymphatic system and that anti-CINC antibody treatment exerted a protective effect against small intestinal ischemia-reperfusion injury.
Asunto(s)
Traslocación Bacteriana/fisiología , Quimiocinas CXC/inmunología , Intestino Delgado/fisiopatología , Activación Neutrófila/fisiología , Daño por Reperfusión/fisiopatología , Animales , Anticuerpos/uso terapéutico , Quimiocina CXCL1 , Citocinas/sangre , Endotoxinas/sangre , Enterococcus faecalis , Escherichia coli , Intestino Delgado/microbiología , Intestino Delgado/patología , Masculino , Morganella morganii , Peroxidasa/metabolismo , Ratas , Ratas Wistar , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/microbiologíaRESUMEN
Steroid receptor RNA activator (SRA) was first isolated as a steroid receptor co-activator that functioned as an RNA transcript. Later, we demonstrated that SRA needs to be translated in order to co-activate androgen receptor (AR). Here, we showed that three isoforms of human SRA enhanced AR activities. Small interfering RNA against SRA suppressed AR activities in PC-3 cells transfected with pSG5AR and in LNCaP cells that have an endogenous mutated-AR. Western blot showed that SRA protein was expressed at a higher level in PC-3 than in LNCaP cells, suggesting that SRA may be related to hormone-independent growth of prostate cancer.
Asunto(s)
Regulación Neoplásica de la Expresión Génica , Neoplasias de la Próstata/genética , ARN no Traducido/genética , Receptores Androgénicos/fisiología , Secuencia de Bases , Biomarcadores de Tumor/análisis , Western Blotting , Progresión de la Enfermedad , Humanos , Masculino , Datos de Secuencia Molecular , Neoplasias de la Próstata/patología , ARN Largo no Codificante , ARN Neoplásico/análisis , ARN no Traducido/metabolismo , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Riesgo , Muestreo , Sensibilidad y Especificidad , Células Tumorales Cultivadas/citologíaRESUMEN
The treatment method for early stage tongue cancer is still controversial in Japan. The aim of this study is to compare the prognosis for patients with early tongue cancer treated with brachytherapy and surgery. A retrospective study was conducted to compare the efficacy of low-dose-rate brachytherapy (LDR), high-dose-rate brachytherapy (HDR), and surgery for early tongue cancer. A total of 180 patients with stage I-II tongue cancer were divided into three treatment groups: LDR (78), HDR (26), and surgery (71). Local recurrence was seen in thirteen patients (17%) of the LDR, nine (35%) of the HDR, and four (6%) of the surgery group. After salvage therapy, final local cure was obtained for 71 patients (91%) of the LDR, 22 (85%) of the HDR, and 71 (100%) of the surgery group. Neck failure was recorded for eight patients in the LDR, six in the HDR, and three in the surgery group. The respective 5-year overall survival rates for the LDR, HDR and surgery groups were 84.0%, 72.9%, 95.4% for stage I, and 72.2%, 51.5%, 93.8% for stage II. These findings show that surgery is the optimal treatment method for patients with stage I-II tongue cancer.
Asunto(s)
Braquiterapia/métodos , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirugía , Neoplasias de la Lengua/radioterapia , Neoplasias de la Lengua/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Terapia por Láser , Metástasis Linfática , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Pronóstico , Dosificación Radioterapéutica , Estudios Retrospectivos , Análisis de Supervivencia , Neoplasias de la Lengua/patologíaRESUMEN
OBJECTIVE: The aim of the present study was to evaluate and compare the morphological and functional recovery following partial glossectomy in rabbits with the CO(2) laser and electrocautery. METHODS: Partial glossectomy with the CO(2) laser or electrocautery in rabbits was performed to investigate changes in the body weight and tongue width after surgery. The study models were classified into three groups. In group 1, the excised edges of the wound were left unsutured after partial glossectomy with the CO(2) laser. In group 2, the wound was closed after CO(2) laser surgery. In group 3, as a control group, the wound was closed after partial glossectomy with electrocautery. The specimens of the tongues obtained from the rabbit were microscopically assessed. RESULTS: No significant differences were found in the percent change in the body weight among the three groups. There was a significant difference in the tongue width between groups 1 and 3 at each time point: 2 weeks (p < 0.05), 4 weeks (p < 0.01), and 8 weeks (p < 0.001) postoperatively. Furthermore, there was a significant difference in the tongue width between groups 2 and 3 at 8 weeks (p < 0.02) postoperatively. Histologically, the scar tissue of the wound was extensive in the control group, although it was localized in the laser group. CONCLUSION: Postoperative dysfunction was reduced when excised edges were left unsutured after partial glossectomy with the CO(2) laser.
Asunto(s)
Electrocoagulación , Glosectomía/métodos , Terapia por Láser , Lengua/patología , Cicatrización de Heridas , Animales , Peso Corporal , Dióxido de Carbono , Masculino , Conejos , Lengua/cirugíaRESUMEN
Attention-deficit hyperactivity disorder (ADHD) is one of the most common childhood behavioral disorders. Genetic factors contribute to the underlying liability to develop ADHD. Reports implicate variants of genes important for the synthesis, uptake, transport and receptor binding of dopamine in the etiology of ADHD, including DRD4, DAT1, DRD2, and DRD5. In the present study, we genotyped a large multiplex sample of ADHD affected children and their parents for polymorphisms in genes previously reported to be associated with ADHD. Associations were tested by the transmission disequilibrium test (TDT). The sample is sufficient to detect genotype relative risks (GRRs) for putative risk alleles. The DRD4 gene 120-bp insertion/deletion promoter polymorphism displayed a significant bias in transmission of the insertion (chi(2)=7.58, P=0.006) as suggested by an analysis of a subset of these families. The seven repeat allele of the DRD4 48-bp repeat polymorphism (DRD4.7) was not significantly associated with ADHD in the large sample in contrast to our earlier findings in a smaller subset. We replicate an association of a dinucleotide repeat polymorphism near the DRD5 gene with ADHD by showing biased nontransmission of the 146-bp allele (P=0.02) and a trend toward excess transmission of the 148-bp allele (P=0.053). No evidence for an association was found for polymorphisms in DRD2 or DAT1 in this sample. The DRD5 146-bp (DRD5.146) allele and the DRD4 240-bp (DRD4.240) allele of the promoter polymorphism emerge as the two DNA variants showing a significant association in this large sample of predominantly multiplex families with ADHD, with estimated GRRs of 1.7 and 1.37, respectively.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/genética , Desequilibrio de Ligamiento , Polimorfismo Genético , Receptores de Dopamina D1/genética , Receptores de Dopamina D2/genética , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Niño , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática , Femenino , Predisposición Genética a la Enfermedad/epidemiología , Haplotipos , Humanos , Masculino , Glicoproteínas de Membrana/genética , Proteínas de Transporte de Membrana/genética , Proteínas del Tejido Nervioso/genética , Receptores de Dopamina D4 , Receptores de Dopamina D5 , Factores de RiesgoRESUMEN
Various treatment procedures for oral leukoplakia have been reported. However, after some treatments, oral leukoplakia show recurrence and/or malignant transformation, even following complete resection. Furthermore, patients with oral leukoplakia may develop new lesions in other oral cavity locations. Laser surgery for oral mucosal lesions has been reported to have many advantages, and it is widely used in the treatment of oral leukoplakia. In previous studies, recurrence and malignant transformation from the lesion have occasionally been observed following laser surgery. We reviewed the records of oral leukoplakia patients treated with laser surgery to assess its clinical usefulness. It has been reported that the rate of recurrence was 7.7-38.1%, while malignant transformation was 2.6-9% for oral leukoplakia treated with laser surgery. In the present study, there was 29.3% recurrence and 1.2% malignant transformation after laser surgery. This was similar to previous findings. This suggests that non-homogeneous leukoplakia on nonkeratinized epithelia, i.e. the tongue mucosa has a high risk for malignant transformation, so lesions should be excised after detecting abnormal epithelia using vital tissue staining. The wound healing process after laser surgery was satisfactory and no significant complications were observed. Management of oral leukoplakia prevents not only recurrence and malignant transformation, but also postoperative dysfunction: laser surgery is an excellent procedure that is able to overcome these problems.
Asunto(s)
Terapia por Láser , Leucoplasia Bucal/cirugía , Mucosa Bucal/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Leucoplasia Bucal/patología , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/patología , Recurrencia Local de Neoplasia/patología , Periodo PosoperatorioRESUMEN
BACKGROUND: It has been recently suggested that cardiac troponin T (cTnT) may be more sensitive than troponin I (cTnI) for subclinical myocardial cell injury in patients on chronic dialysis. METHODS: We prospectively compared the predictive value of cTnT with cTnI, atrial (ANP) and brain natriuretic peptide (BNP) in 100 consecutive outpatients on chronic dialysis without acute coronary syndromes over a period of 3 months, and assessed whether the combination of cTnT with clinical information including age, duration of dialysis, and medical histories was useful for risk stratification of these patients. During the 2-year follow-up period, 19 patients died, mostly due to cardiac causes (53%). RESULTS: The area under the receiver operator characteristic (ROC) curve for the cTnT as predictor of both overall and cardiac death was significantly greater than the area under the cTnI curve (p < 0.0001 and p = 0.01), the BNP curve (p < 0.001 and p < 0.01) or the ANP curve (p < 0.0001 and p < 0.005). In a stepwise multivariate Cox regression analysis, only cTnT (p < 0.05 and p < 0.01) and a history of heart failure requiring hospitalization (p < 0.05 and p < 0.005) were independent predictors of both all cause and cardiac mortality. Using parameters of cTnT > or =0.1 microg/l and/or history of heart failure, the overall and cardiac mortality rate for the low risk group (n=66) were 4.5% and 1.5%, respectively, 40% and 16% for the intermediate risk group (n=25), and 67% and 56% for the high risk group (n=9). CONCLUSION: cTnT concentrations offer a higher prognostic accuracy than cTnI, ANP and BNP in patients on chronic dialysis. The combination of elevated cTnT and a history of heart failure may be a highly effective means of risk stratification of these patients.
Asunto(s)
Enfermedades Cardiovasculares/sangre , Fallo Renal Crónico/sangre , Troponina T/sangre , Adulto , Anciano , Factor Natriurético Atrial/sangre , Enfermedades Cardiovasculares/mortalidad , Femenino , Insuficiencia Cardíaca/sangre , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/mortalidad , Masculino , Persona de Mediana Edad , Miocardio/metabolismo , Péptido Natriurético Encefálico/sangre , Valor Predictivo de las Pruebas , Estudios Prospectivos , Curva ROC , Diálisis Renal , Factores de Riesgo , Tasa de Supervivencia , Troponina I/sangreRESUMEN
OBJECTIVE: The purpose of this study was to evaluate the efficacy of fidarestat, a novel aldose reductase (AR) inhibitor, in a double-blind placebo controlled study in patients with type 1 and type 2 diabetes and associated peripheral neuropathy. RESEARCH DESIGN AND METHODS: A total of 279 patients with diabetic neuropathy were treated with placebo or fidarestat at a daily dose of 1 mg for 52 weeks. The efficacy evaluation was based on change in electrophysiological measurements of median and tibial motor nerve conduction velocity, F-wave minimum latency, F-wave conduction velocity (FCV), and median sensory nerve conduction velocity (forearm and distal), as well as an assessment of subjective symptoms. RESULTS: Over the course of the study, five of the eight electrophysiological measures assessed showed significant improvement from baseline in the fidarestat-treated group, whereas no measure showed significant deterioration. In contrast, in the placebo group, no electrophysiological measure was improved, and one measure significantly deteriorated (i.e., median nerve FCV). At the study conclusion, the fidarestat-treated group was significantly improved compared with the placebo group in two electrophysiological measures (i.e., median nerve FCV and minimal latency). Subjective symptoms (including numbness, spontaneous pain, sensation of rigidity, paresthesia in the sole upon walking, heaviness in the foot, and hypesthesia) benefited from fidarestat treatment, and all were significantly improved in the treated versus placebo group at the study conclusion. At the dose used, fidarestat was well tolerated, with an adverse event profile that did not significantly differ from that seen in the placebo group. CONCLUSIONS: The effects of fidarestat-treatment on nerve conduction and the subjective symptoms of diabetic neuropathy provide evidence that this treatment alters the progression of diabetic neuropathy.
Asunto(s)
Aldehído Reductasa/antagonistas & inhibidores , Neuropatías Diabéticas/tratamiento farmacológico , Inhibidores Enzimáticos/uso terapéutico , Imidazoles/uso terapéutico , Imidazolidinas , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Neuropatías Diabéticas/fisiopatología , Método Doble Ciego , Electrofisiología , Femenino , Hemoglobina Glucada/análisis , Humanos , Hipoestesia , Imidazoles/efectos adversos , Masculino , Persona de Mediana Edad , Dolor , Parestesia , PlacebosRESUMEN
Mechanisms of gravitactic behaviors of aquatic microorganisms were investigated in terms of their mechanical basis of gravity-dependent orientation. Two mechanical mechanisms have been considered as possible sources of the orientation torque generated on the inert body. One results from the differential density within an organism (the gravity-buoyancy model) and the other from the geometrical asymmetry of an organism (the drag-gravity model). We first introduced a simple theory that distinguishes between these models by measuring sedimentation of immobilized organisms in a medium of higher density than that of the organisms. Ni2+-immobilized cells of Paramecium caudatum oriented downwards while floating upwards in the Percoll-containing hyper-density medium but oriented upwards while sinking in the hypo-density control medium. This means that the orientation of Paramecium is mechanically biased by the torque generated mainly due to the anterior location of the reaction center of hydrodynamic stress relative to those of buoyancy and gravity; thus the torque results from the geometrical fore-aft asymmetry and is described by the drag-gravity model. The same mechanical property was demonstrated in gastrula larvae of the sea urchin by observing the orientation during sedimentation of the KCN-immobilized larvae in media of different density: like the paramecia, the gastrulae oriented upwards in hypo-density medium and downwards in hyper-density medium. Immobilized pluteus larvae, however, oriented upwards regardless of the density of the medium. This indicates that the orientation of the pluteus is biased by the torque generated mainly due to the posterior location of the reaction center of gravity relative to those of buoyancy and hydrodynamic stress; thus the torque results from the fore-aft asymmetry of the density distribution and is described by the gravity-buoyancy model. These observations indicate that, during development, sea urchin larvae change the mechanical mechanism for the gravitactic orientation. Evidence presented in the present paper demonstrates a definite relationship between the morphology and the gravitactic behavior of microorganisms.
Asunto(s)
Gravitación , Larva/fisiología , Locomoción , Modelos Biológicos , Paramecium/fisiología , Erizos de Mar , Animales , Fenómenos Biomecánicos , Larva/efectos de los fármacos , Matemática , Níquel/farmacología , Paramecium/efectos de los fármacos , Cianuro de Potasio/farmacología , Erizos de Mar/crecimiento & desarrolloRESUMEN
An association between Epstein-Barr virus (EBV) infection and fibroblast proliferation in the interstitial spaces of the lung has been suggested in idiopathic interstitial pneumonia. In this study we show that EBV can infect human lung fibroblasts in vitro. A primary-cultured human lung fibroblast cell line, designated CCD-32Lu, expressed EBV nuclear antigen 1 after coculture with lethally irradiated EBV producing cells. The infection further induced CCD-32Lu cells to produce the fibrogenic cytokines basic fibroblast growth factor (bFGF) and interleukin-1beta. These findings indicate that lung fibroblasts may be a target for EBV infection and suggest that EBV may play a role in increased production of these cytokines and induce fibroblast proliferation in idiopathic interstitial pneumonia.
Asunto(s)
Infecciones por Virus de Epstein-Barr/metabolismo , Factor 2 de Crecimiento de Fibroblastos/biosíntesis , Fibroblastos/virología , Herpesvirus Humano 4/fisiología , Interleucina-1/biosíntesis , Anticuerpos Bloqueadores/farmacología , Anticuerpos Antivirales/inmunología , Western Blotting , División Celular , Línea Celular , Técnicas de Cocultivo , Ensayo de Inmunoadsorción Enzimática , Antígenos Nucleares del Virus de Epstein-Barr/análisis , Antígenos Nucleares del Virus de Epstein-Barr/metabolismo , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Humanos , Pulmón/citología , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/metabolismo , Enfermedades Pulmonares Intersticiales/virología , Pruebas de Neutralización , Factor de Crecimiento Transformador beta/biosíntesis , Factor de Crecimiento Transformador beta1RESUMEN
The purpose of this study was to evaluate whether the plasma brain natriuretic peptide (BNP) concentration is a useful marker of right ventricular (RV) overload and whether it has prognostic value as a predictor of death in patients with chronic respiratory disease (CRD). We measured the plasma BNP and atrial natriuretic peptide (ANP) concentrations in 31 consecutive patients with CRD who underwent right-heart catheterization to evaluate pulmonary hypertension. All patients were followed for >12 months. The plasma BNP concentration closely correlated with the mean pulmonary artery pressure and pulmonary vascular resistance (r=0.62, P<0.0005 and r=0. 85, P<0.0001), and showed a weak linear correlation with cardiac output (r=-0.36, P<0.05). During the follow-up period, 5 (16%) end-stage CRD deaths (4 RV heart failure and 1 respiratory infection) and 2 non-end-stage CRD deaths occurred. In a stepwise multivariate Cox proportional-hazards regression analysis including age, sex, BNP, ANP, hemodynamic variables and the ratio of PaO(2) to fraction of inspired oxygen, only BNP (P<0.05) was an independent predictor of end-stage CRD death. The upward and leftward shift in the receiver operating characteristic curve between patients with end-stage CRD death and those without was greater for BNP than for ANP. Our findings suggest that the plasma BNP concentration may be an inexpensive, simple and useful marker of RV overload and end-stage CRD death in CRD patients. These preliminary results need to be confirmed in a large series of CRD patients.
Asunto(s)
Ventrículos Cardíacos/fisiopatología , Enfermedades Pulmonares/sangre , Péptido Natriurético Encefálico/sangre , Anciano , Enfermedad Crónica , Femenino , Humanos , Enfermedades Pulmonares/mortalidad , Enfermedades Pulmonares/fisiopatología , Masculino , Persona de Mediana EdadRESUMEN
Cell-cell and cell-matrix interactions play a critical role in tissue morphogenesis and in homeostasis of adult tissues. The integrin family of adhesion receptors regulates cellular interactions with the extracellular matrix, which provides three-dimensional information for tissue organization. It is currently thought that pancreatic islet cells develop from undifferentiated progenitors residing within the ductal epithelium of the fetal pancreas. This process involves cell budding from the duct, migration into the surrounding mesenchyme, differentiation, and clustering into the highly organized islet of Langerhans. Here we report that alpha(v)beta(3) and alpha(v)beta(5), two integrins known to coordinate epithelial cell adhesion and movement, are expressed in pancreatic ductal cells and clusters of undifferentiated cells emerging from the ductal epithelium. We show that expression and function of alpha(v)beta(3) and alpha(v)beta(5) integrins are developmentally regulated during pancreatic islet ontogeny, and mediate adhesion and migration of putative endocrine progenitor cells both in vitro and in vivo in a model of pancreatic islet development. Moreover, we demonstrate the expression of fibronectin and collagen IV in the basal membrane of pancreatic ducts and of cell clusters budding from the ductal epithelium. Conversely, expression of vitronectin marks a population of epithelial cells adjacent to, or emerging from, pancreatic ducts. Thus, these data provide the first evidence for the contribution of integrins alpha(v)beta(3) and alpha(v)beta(5) and their ligands to morphogenetic events in the human endocrine pancreas.