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Supplementation of betaine is associated with improved cardiac health, potentially due to its function in re-methylation of homocysteine, an independent risk factor for cardiovascular diseases. We investigated the effects of oral betaine supplementation on blood pressure homeostasis in spontaneously hypertensive (SHR) rats and Wistar Kyoto (WKY) rats in an 8 week-feeding trial with control (SHR-con and WKY-con) and 1% betaine supplemented (SHR-b and WKY-b) diets. Systolic, diastolic, and mean blood pressure in the SHR-b group were significantly lower at week 8 (p = 0.013, p = 0.011, p = 0.010, respectively). Furthermore, serum nitric oxide (NO) levels were significantly (p < 0.05) improved in the WKY-b and SHR-b groups, suggesting a healthy endothelial function. Additionally, the serum angiotensin I converting enzyme level in SHR-b rats was also significantly lowered, which may have been another reason for lower blood pressure. A significantly higher non-HDL level in the SHR-b group might reflect enhanced lipid secretion into the circulation in the form of very-low-density lipoprotein (VLDL). Betaine is known for its effect on the synthesis of phosphatidylcholine, a key component of VLDL. However, the long-term net outcomes of both blood pressure lowering and serum lipid increment should be further studied.
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Anterior commissure is involved in about 20% of early-stage glottic squamous cell carcinomas (EGSCCs). Treatment outcomes and prognostic factors for EGSCC with anterior commissure involvement (ACI) were evaluated by focusing on hyperfractionated radiotherapy (74.4 Gy in 62 fractions). One-hundred and fifty-three patients with T1-T2 EGSCC were included in this study. The median total doses for T1a, T1b, and T2 were 66, 74.4, and 74.4 Gy, respectively. Overall, 49 (32%) patients had T1a, 38 (25%) had T1b, and 66 (43%) had T2 disease. The median treatment duration was 46 days. The median follow-up duration was 5.1 years. The 10-year overall and cause-specific survival rates were 72% and 97%, respectively. The 10-year local control rates were 94% for T1a, 88% for T1b, and 81% for T2 disease. Local control rates in patients with ACI were slightly better than those in patients without ACI with T1a and T1b diseases; however, the difference was not significant. The 10-year laryngeal preservation rate was 96%. Six patients experienced grade 3 mucositis, and four patients had grade 3 dermatitis. Hyperfractionated radiotherapy was effective for T1 disease with ACI, but insufficient for T2 disease with ACI. Our treatment strategy resulted in excellent laryngeal preservation.
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Previous research has demonstrated that Porphyromonas gulae (P. gulae) significantly contributes to the development of periodontal disease in dogs. Porphyromonas gulae is divided into three subtypes according to the 41-kDa filamentous appendage (fimA), defined as types A, B, and C. This study aimed to elucidate the association between fimA type of P. gulae with the number of permanent teeth, reflecting the severity of periodontal disease. Two hundred twenty-five dogs were categorized by P. gulae fimA type as negative, type A dominant, type B dominant, and type C dominant. The stage of periodontal disease in P. gulae-positive dogs increased with age, particularly in type C dominant dogs. Correspondingly, the number of permanent teeth in P. gulae fimA type C-dominant dogs was significantly lower than that of P. gulae-negative dogs, suggesting there is a significant association between fimA type of P. gulae and the number of permanent teeth resulting from the development of periodontal disease.
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We evaluated the clinical significance of the new non-invasive vascular indices to explore their potential utility using repeated cuff-oscillometric inflation. In 250 consecutive outpatients, we performed a cross-sectional, retrospective, single-center, observational study to investigate sequential differences in arterial stiffness using blood pressure, arterial velocity pulse index (AVI), and arterial pressure volume index (API) with repeated measurements. Males accounted for 62.7% of the patients, and the mean age was 68.1 ± 12.1 years. The mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the first reading in repeated measurements were 133.07 ± 21.20 mmHg and 73.94 ± 13.56 mmHg, respectively. The mean AVI and API were 23.83 ± 8.30 and 31.12 ± 7.86, respectively. In each measurement of these parameters, although DBP and AVI did not show significant changes throughout repeated measurements, SBP and API decreased significantly according to the measurement orders. Furthermore, changes in SBP and API were significantly correlated in several of the models. In this study, it was concluded that upper-arm SBP decline associated with repeated cuff-oscillometric inflation was significantly correlated with the arterial stiffness index. The findings of this study will allow clinicians to easily recognize the progression of atherosclerosis through regular, routine practice. In conclusion, this study suggests that changes in repeated SBP measurements may be predictive of arterial stiffness and atherosclerosis.
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Abatacept (ABT) is a recombinant fusion protein consisting of the Fc domain fragment of human IgG1 and the extracellular domain of human cytotoxic T lymphocyte antigen-4 (CTLA-4). The function of ABT is similar to that of CTLA-4, which selectively regulates T-cell activation by inhibiting the co-stimulation of CD80/CD86 on antigen-presenting cells and CD28 on T lymphocytes. ABT is used for the treatment of rheumatoid arthritis (RA) and juvenile idiopathic arthritis. We report two cases of ulcerative colitis (UC) that developed while using ABT. Case 1 is of a 58-year-old man who developed diarrhea and hematochezia 2 months after starting ABT therapy for RA. Case 2 is of a 66-year-old man who experienced hematochezia 15 months after starting ABT therapy for RA. In both cases, no obvious gastrointestinal symptoms were observed before ABT therapy was initiated. Colonoscopy after disease onset showed UC findings in both cases. The patients' condition improved following ABT withdrawal and treatment for UC. Several cases of UC development during ABT therapy have been reported. The complication of UC should be considered when diarrhea and hematochezia are observed in patients with RA being treated with CTLA-4Ig agents.
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Antirreumáticos , Artritis Reumatoide , Colitis Ulcerosa , Abatacept/farmacología , Abatacept/uso terapéutico , Anciano , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Antígenos CD28/uso terapéutico , Antígeno CTLA-4/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Diarrea/inducido químicamente , Diarrea/tratamiento farmacológico , Hemorragia Gastrointestinal , Humanos , Inmunoglobulina G , Masculino , Persona de Mediana Edad , Proteínas Recombinantes de Fusión/uso terapéuticoRESUMEN
BACKGROUND: Approximately 60% of outpatients with advanced cancer experience pain; therefore, self-management of opioid use is important for appropriate pain relief. To date, no studies have clearly described the concept of opioid self-management or assessed the factors involved, including the improvement of self-management abilities. This study developed, and evaluated the validity and reliability of an opioid self-management scale for advanced cancer patients with pain (OSSA). Opioid self-management in advanced cancer patients with pain was defined as the management of opioid medication performed by patients with advanced cancer to relieve cancer pain on their own. METHODS: Three phases were required for validation and reliability of the OSSA: 1) testing content validity, 2) testing face validity, and 3) testing construct validity, concurrent validity and reliability. RESULTS: After a three-phase process, the OSSA consisted of 33 items on six subscales. The structural equation modeling was such that the χ2 value was 709.8 (p < 0.001, df = 467), goodness-of-fit index was 0.78, adjusted goodness-of-fit index was 0.73, root mean squares of approximation was 0.063, and comparative fit index was 0.92. The Pearson correlation coefficients between the total OSSA score and the 24-hour average pain or pain relief over 24 hours were - 0.21 (p < 0.05) and 0.26 (p < 0.01), respectively. Cronbach's α was 0.93. The intraclass correlation coefficient range was 0.59-0.90. CONCLUSION: The findings of this study show that the OSSA has acceptable validity and reliability, and that better self-management leads to greater pain relief. The OSSA can be considered effective for use in research, but shortened version should be prepared for realistic and practical clinical use.
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Neoplasias , Automanejo , Analgésicos Opioides/uso terapéutico , Humanos , Neoplasias/complicaciones , Dolor/tratamiento farmacológico , Dolor/etiología , Psicometría , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
Various COVID-19 vaccines are associated with numerous adverse side effects. Associations between vaccinations and neurological disorders, such as transverse myelitis, stroke, Bell's palsy, acute disseminated encephalomyelitis, and Guillain-Barré syndrome, have been reported. A 27-year-old Japanese woman presented with paresthesia four days after receiving a second dose of the COVID-19 vaccine. One month after vaccination, she started to feel left lower limb weakness, and her symptoms almost improved after two steroid pulse therapies. Spinal cord tumor biopsy could potentially help make a definitive diagnosis in clinical situations. However, it is very important to review the patient's medical history, including vaccinations received, before performing a direct spinal cord biopsy, which is invasive and does not guarantee a definitive diagnosis.
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This case involved a 72-year-old woman. From the day after mitral annuloplasty, a fever over 37°C and ballismus-like involuntary movements of the right upper and lower limbs appeared. A few month later, involuntary movements spread throughout the body, and she developed impairment of consciousness and difficulty speaking and eating. Levels of protein in cerebrospinal fluid were high. Positive results were seen for serum mumps immunoglobulin G and M antibody. Because steroid pulse therapy proved effective, we suspected autoimmune encephalitis associated with mumps virus infection.
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Discinesias , Encefalitis , Paperas , Anciano , Encefalitis/complicaciones , Encefalitis/etiología , Femenino , Enfermedad de Hashimoto , Humanos , Inmunoglobulina G , Paperas/complicaciones , Paperas/diagnóstico , Paperas/inmunología , Virus de la Parotiditis/inmunologíaRESUMEN
Polydopamine (PDA)-a known adhesive coating material-was used herein to strongly immobilize a Pt-particle catalyst on an acrylonitrile-butadiene-styrene copolymer (ABS) substrate. Previous studies have shown that the poor adhesion between Pt particles and ABS surfaces is a considerable problem, leading to low catalytic durability for H2O2 decomposition during contact-lens cleaning. First, the ABS substrate was coated with PDA, and the PDA film was evaluated by X-ray photoelectron spectroscopy. Second, Pt particles were immobilized on the PDA-coated ABS substrate (ABS-PDA) using the electron-beam irradiation reduction method. The Pt particles immobilized on ABS-PDA (Pt/ABS-PDA) were observed using a scanning electron microscope. The Pt-loading weight was measured by inductively coupled plasma atomic emission spectroscopy. Third, the catalytic activity of the Pt/ABS-PDA was evaluated as the residual H2O2 concentration after immersing it in a 35,000-ppm H2O2 solution (the target value was less than 100 ppm). The catalytic durability was evaluated as the residual H2O2 concentration after repeated use. The PDA coating drastically improved both the catalytic activity and durability because of the high Pt-loading weight and strong adhesion among Pt particles, PDA, and the ABS substrate. Plasma treatment prior to PDA coating further improved the catalytic durability.
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RATIONALE: We report this 1st case because perampanel may be effective against the seizures and abnormal behavior that occur in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. PATIENT CONCERNS: The patient was a healthy 26-year-old woman who suddenly developed seizures and exhibited abnormal behavior. DIAGNOSES: NMDAR encephalitis was diagnosed based on positive NMDAR antibody on cerebrospinal fluid analysis. INTERVENTIONS: Treatment with anticonvulsants and sedatives was started immediately, along with steroid pulse therapy and plasmapheresis, but these measures did not adequately control the repeated seizures and abnormal behavior. However, with the addition of oral perampanel, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, the seizures and abnormal behavior promptly disappeared. OUTCOMES: The patient was transferred to the rehabilitation hospital and returned to her job. LESSONS: It appears that perampanel rapidly eliminated these clinical features by inhibiting inflow of abnormal glutamic acid and attenuating nerve hyperexcitability by acting as a selective and noncompetitive antagonist of AMPA receptors that had increased in the postsynaptic membrane due to anti-NMDAR encephalitis. To the best of our knowledge, there are no other reports showing that perampanel was effective against anti-NMDAR encephalitis. This case suggests that perampanel may be effective against the seizures and abnormal behavior that occur in anti-NMDAR encephalitis.
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Encefalitis Antirreceptor N-Metil-D-Aspartato/tratamiento farmacológico , Fármacos del Sistema Nervioso Central/uso terapéutico , Piridonas/uso terapéutico , Adulto , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Femenino , Humanos , Nitrilos , Convulsiones/diagnóstico , Convulsiones/tratamiento farmacológicoRESUMEN
Superb microvascular imaging (SMI) reduces motion artifacts significantly and allows visualization of low-velocity blood flow in vessels; thus, thrombi are clearly demonstrated compared to conventional B-mode and color Doppler imaging. Ultrasonographic images of the lower extremities of a 69-year-old woman with acute ischemic stroke complicated with deep vein thrombosis (DVT) are presented. Because SMI allows visualization of low-velocity blood flow, echo contrast between the thrombus and the surrounding flow makes it possible to clearly visualize the thrombus. SMI is a useful method to evaluate DVT, especially early after thrombus formation when it is difficult to delineate size and length because of echolucency.
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Ultrasonografía/métodos , Trombosis de la Vena/diagnóstico por imagen , Anciano , Isquemia Encefálica/complicaciones , Isquemia Encefálica/diagnóstico por imagen , Femenino , Humanos , Microvasos/diagnóstico por imagen , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico por imagen , Trombosis de la Vena/complicacionesRESUMEN
BACKGROUND: Endothelial dysfunction and increased arterial stiffness gradually develop before the manifestation of catastrophic cardiovascular events. Therefore, detection and assessment of vascular function are required to address pre-existing pathological conditions. However, the currently available diagnostic devices and methods are insufficient due to variability among investigators and the time-consuming nature of manual procedures. METHODS: Recently, novel devices were developed for the detection of both arterial stiffness and endothelial dysfunction in a single blood pressure measurement using a cuff-oscillometric technique (AVE-1500, Shisei Datum, Japan). API (arterial pressure volume index) is defined as the reciprocal of the slope of the tangent of the brachial artery pressure-volume curve, and AVI (arterial velocity pulse index) is defined as the ratio of the difference between the ejection and reflection waves. In the present study, we performed retrospective, cross-sectional analyses of subjects (n = 102; mean age = 70.5 ± 10.4 years) with detailed coronary angiographic examinations and clinical background parameters. RESULTS: After adjusting for various variables using multiple linear regression analyses, we found that API, but not AVI, was significantly correlated with coronary artery severity and complexity scores. CONCLUSIONS: We propose that API may be a new vascular index useful for monitoring and assessing the severity and complexity of atherosclerosis in subjects with coronary artery disease and for evaluating atherosclerotic diseases.
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BACKGROUND/OBJECTIVES: Immunosuppressant medications (ISPs) increase the occurrence of Pneumocystis jirovecii pneumonia (PCP) in rheumatoid arthritis (RA) patients. The prophylactic administration of trimethoprim/sulfamethoxazole (TMP/SMX) for PCP is effective but has serious adverse effects and so should be selectively used for patients at high risk. The aims of this study were to clarify the risk factors for PCP in RA patients and to establish the indications for administering TMP/SMX. METHODS: This retrospective cohort study analyzed data from 2640 patients (2010-2014) diagnosed as having RA who had not received a prophylactic administration of TMP/SMX. The risk factors for PCP were evaluated by comparing the clinical parameters between patients with PCP (PCP group, n = 19) and those without (non-PCP group, n = 2621). RESULTS: The PCP group was older (70 vs. 64 years), received higher doses of prednisolone (6.2 vs. 2.4 mg/d) and methotrexate (7.7 vs. 5.2 mg/wk), and had a greater number of ISPs (1.3 vs. 0.8) (p < 0.05). We stratified the PCP risk using a scoring system based on odds ratios (ORs) calculated for these parameters (methotrexate ≥6 mg/wk OR = 4.5, 1 point; age ≥65 years, OR = 3.7, 1 point; ≥2 ISPs, OR = 3.7, 1 point; prednisolone ≥5 mg/d, OR = 12.4, 3 points). The incidence of PCP among patients scoring 0 to 2 points was 0.04%; 3 to 4 points, 2.3%; and 5 points or more, 5.8%. CONCLUSIONS: The prophylactic administration of TMP/SMX for PCP is recommended for RA patients who score at least 5 points with our system.
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Artritis Reumatoide/tratamiento farmacológico , Inmunosupresores/efectos adversos , Neumonía por Pneumocystis/inmunología , Neumonía por Pneumocystis/prevención & control , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pneumocystis carinii , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
Neuromedin U (NMU) is a neuropeptide that is expressed and secreted in the brain and gut. We previously demonstrated that the intracerebroventricular (i.c.v.) administration of NMU inhibited inflammation-mediated memory impairment in mice. In order to utilize NMU as a clinical treatment tool for inflammation-mediated amnesia, we herein focused on non-invasive intranasal delivery because the i.c.v. administration route is invasive and impractical. In the present study, we prepared two NMU derivatives containing cell-penetrating peptides (CPPs), octaarginine (R8), and each penetration-accelerating sequence, namely FFLIPKG (PASR8-NMU) and FFFFG (F4R8-NMU), for intranasal (i.n.) administration. In the Y-maze test, the i.c.v. administration of lipopolysaccharide (LPS) (10µg/mouse) significantly decreased spontaneous alternation behavior, and this was prevented by the prior administration of PASR8-NMU or F4R8-NMU (5.6µg/mouse, i.n.). Moreover, the administration of PASR8-NMU or F4R8-NMU (5.6µg/mouse, i.n.) just before the Y-maze test also improved LPS-induced memory impairment. Indocyanine green (ICG)-labeled PASR8-NMU (i.n.) was significantly observed in the hippocampus and paraventricular hypothalamic nucleus 30min after its i.n. administration. PASR8-NMU, but not F4R8-NMU guaranteed the stability of the administration liquid for 24h. These results suggest that PASR8-NMU is effective for i.n. delivery to the brain, and may be useful in the clinical treatment of inflammation-mediated amnesia.
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Péptidos de Penetración Celular/farmacología , Aprendizaje por Laberinto/efectos de los fármacos , Memoria/efectos de los fármacos , Neuropéptidos/farmacología , Núcleo Hipotalámico Paraventricular/metabolismo , Administración Intranasal , Animales , Relación Dosis-Respuesta a Droga , Masculino , Aprendizaje por Laberinto/fisiología , Memoria/fisiología , RatonesRESUMEN
BACKGROUND: The rate of disease progression differs among patients with degenerative cerebellar ataxia. The uncertain natural course in individual patients hinders clinical trials of promising treatments. In this study, we analyzed atrophy changes in brain structures with cluster analysis to find sub-groups of patients with homogenous symptom progression in a broad spectrum of degenerative cerebellar ataxias. METHODS: We examined 48 patients including 21 cases of spinocerebellar ataxia (SCA), 17 cases of the cerebellar type of multiple system atrophy (MSA-C), and 10 cases of cortical cerebellar ataxia (CCA). In all patients, at least two sets of evaluations including magnetic resonance imaging (MRI) and the International Cooperative Ataxia Rating Scale (ICARS) scoring were performed. The median number (min-max) of follow-up studies in each patient was three (2-6), and the mean follow-up period was 3.1 ± 1.6 years. The area of the corpus callosum on midsagittal images and the cerebellar volume were measured using MRI, and these values were divided by the cranial antero-posterior diameter of each patient to correct for individual head size differences as an area index (Adx) and a volume index (Vdx), respectively. The annual changes in Adx, Vdx, and ICARS score were calculated in each patient, and atrophy patterns in patients were categorized with cluster analysis. RESULTS: The annual atrophy rates for the corpus callosum (Adx) and cerebellum (Vdx) and symptom progression differed significantly by subtype of cerebellar ataxia (p = 0.026, 0.019, and 0.021, respectively). However, neither the annual atrophy rate of Adx nor Vdx was significantly correlated with the annual increase in the ICARS score. When the patients were categorized into three clusters based on the annual changes in Adx and Vdx, the annual increase in the ICARS score was significantly different among clusters (2.9 ± 1.7/year in Cluster 1, 4.8 ± 3.2/year in Cluster 2, and 8.7 ± 6.1/year in Cluster 3; p = 0.014). CONCLUSIONS: The annual increase in the ICARS score can be stratified by cluster analysis based on the atrophy rates of the corpus callosum and cerebellum. Further studies are warranted to explore whether these simple MRI methods could be used for random allocation of a broad spectrum of patients with degenerative cerebellar ataxia in clinical trials.
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We have previously shown that neural precursor cell-expressed developmentally downregulated gene 4-2 (Nedd4-2) isoforms with a C2 domain are closely related to ubiquitination of epithelial sodium channel (ENaC), resulting in salt-sensitive hypertension by Nedd4-2 C2 targeting in mice. The sodium voltage-gated channel alpha subunit 5 (SCN5A) gene encodes the α subunit of the human cardiac voltage-gated sodium channel (I Na), and the potassium voltage-gated channel subfamily H member 2 (KCNH2) gene encodes rapidly activating delayed rectifier K channels (I Kr). Both ion channels have also been shown to bind to Nedd4-2 via a conserved Proline-Tyrosine (PY) motif in C-terminal with subsequent ubiquitination and degradation by proteasome. Therefore, loss of Nedd4-2 C2 isoform might be involved in electrophysiological impairment under various conditions. We demonstrate here that Nedd4-2 C2 isoform causes cardiac conduction change in resting condition as well as proarrhythmic change after acute myocardial infarction (MI). The Nedd4-2 C2 knockout (KO) mice showed bradycardia, prolonged QRS, QT intervals, and suppressed PR interval in resting condition. In addition, enhancement of T peak/T end interval was found in mice with surgical ligation of the distal left coronary artery. Morphological analyses based on both ultrasonography of the living heart, as well as histopathological findings revealed that Nedd4-2 C2 KO mice show no significant structural changes from wild-type littermates under resting conditions. These results suggested that Nedd4-2 with C2 domain might play an important role in cardio-renal syndrome through post-transcriptional modification of both ENaC and cardiac ion channels, which are critical for kidney and heart functions.
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Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/fisiopatología , Ubiquitina-Proteína Ligasas Nedd4/genética , Animales , Enfermedades Cardiovasculares/metabolismo , Canales Epiteliales de Sodio/metabolismo , Regulación de la Expresión Génica , Corazón/fisiopatología , Frecuencia Cardíaca , Hipertensión/genética , Hipertensión/metabolismo , Hipertensión/fisiopatología , Masculino , Ratones , Ratones Noqueados , Infarto del Miocardio/genética , Infarto del Miocardio/metabolismo , Infarto del Miocardio/fisiopatología , Ubiquitina-Proteína Ligasas Nedd4/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismoRESUMEN
The interpretation of the local microenvironment of the extracellular matrix for malignant tumor cells is in intimate relation with metastatic spread of cancer cells involving the associated issues of cellular proliferation and drug responsiveness. This study was aimed to assess the combination of both surface topographies (fiber alignments) and different stiffness of the polymeric substrates (poly(l-lactic acid) and poly(ε-caprolactone), PLLA and PCL, respectively) as well as collagen substrates (coat and gel) to elucidate the effect of the cellular morphology on cellular proliferation and drug sensitivities of two different types of breast cancer cells (MDA-MB-231 and MCF-7). The morphological spreading parameter (nucleus/cytoplasm area ratio) induced by the anthropogenic substrates has correlated intimately with the cellular proliferation and the drug sensitivity the half maximal inhibitory concentration (IC50) of cancer cells. This study demonstrated the promising results of the parameter for the evaluation of cancer cell malignancy.
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The epithelial sodium channel (ENaC) plays critical roles in maintaining fluid and electrolyte homeostasis and is located in the aldosterone-sensitive distal nephron (ASDN). We previously found that Nedd4-2 C2 knockout (KO) mice showed salt-sensitive hypertension with paradoxically enhanced ENaC gene expression in ASDN under high oral salt intake. Eplerenone (EPL), a selective aldosterone blocker, is a promising therapeutic option for resistant or/and salt-sensitive hypertension. We examined the effect of EPL on Nedd4-2 C2 KO mice with respect to blood pressure, metabolic parameters, and molecular level changes in ASDN under high oral salt intake. We found that EPL failed to reduce blood pressure in KO mice with high oral salt intake and upregulated ENaC expression in ASDN. Thus, salt-sensitive hypertension in Nedd4-2 C2 KO was EPL-resistant. Gene expression analyses of laser-captured specimens in ASDN suggested the presence of non-aldosterone-dependent activation of ENaC transcription in ASDN of Nedd4-2 C2 KO mice, which was abolished by amiloride treatment. Our results from Nedd4-2 C2 KO mice suggest that enhanced ENaC gene expression is critically involved in salt-sensitive hypertension under certain conditions of specific enzyme isoforms for their ubiquitination.
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Canales Epiteliales de Sodio/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Ubiquitina-Proteína Ligasas Nedd4/genética , Espironolactona/análogos & derivados , Animales , Presión Sanguínea/efectos de los fármacos , Canales Epiteliales de Sodio/genética , Eplerenona , Regulación de la Expresión Génica , Técnicas de Inactivación de Genes , Hipertensión/metabolismo , Masculino , Ratones , Ratones Noqueados , Cloruro de Sodio Dietético/farmacología , Espironolactona/farmacologíaRESUMEN
A 55-year-old man was admitted with paralysis of the left lower leg. He had purpura in the left lower extremity for three years, left calf pain for two years, and dysesthesia in the left plantar region and first toe for one year. A physical examination revealed livedo reticularis on the left leg and mononeuritis multiplex was diagnosed in the bilateral tibial and left peroneal nerve area. Anti-neutrophil cytoplasmic antibody was negative. A nerve conduction study showed decreased amplitude of compound muscle-action potential in the bilateral tibial and the left peroneal nerve, sensory nerve action potential in the bilateral sural nerve. A skin biopsy revealed inflammatory cells on blood vessel walls and cutaneous arteritis was diagnosed. Cyclophosphamide pulse therapy with steroid and anti-coagulation improved the neurological symptoms. A skin biopsy should be considered when patients present with mononeuritis multiplex in the lower extremities and cutaneous findings such as livedo reticularis in the symptomatic area.
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Arteritis/complicaciones , Biopsia , Mononeuropatías/diagnóstico , Mononeuropatías/etiología , Piel/irrigación sanguínea , Piel/patología , Anticoagulantes/administración & dosificación , Arteritis/tratamiento farmacológico , Arteritis/patología , Ciclofosfamida/administración & dosificación , Diagnóstico Diferencial , Humanos , Masculino , Metilprednisolona/administración & dosificación , Persona de Mediana Edad , Mononeuropatías/tratamiento farmacológico , Mononeuropatías/patología , Prednisolona/administración & dosificación , Quimioterapia por Pulso , Resultado del TratamientoRESUMEN
RATIONALE: Subcutaneous implantable electrocardiographs are highly effective in detecting covert atrial fibrillation (AF) in cryptogenic stroke. However, these invasive devices are not indicated for all cryptogenic stroke patients, and noninvasive improvements over conventional Holter-type ambulatory electrocardiography are needed. We evaluated the clinical application and effectiveness of Duranta (ImageONE Co., Ltd.), a wireless patch-type electrocardiographic monitoring system developed in Japan for chronically ill patients or home-based patients at the end of life. A Duranta device was used to detect covert AF in patients with acute ischemic stroke of undetermined source with no sign of AF during cardiographic monitoring ≥24âhours postadmission. PATIENT CONCERNS: A 72-year-old man with severe aortic stenosis was admitted to our hospital with dysarthria and right upper limb weakness. Diffusion-weighted plain head magnetic resonance imaging (MRI) showed acute cerebral infarctions across the left middle cerebral artery territory. Twelve-lead electrocardiography, Holter-type ambulatory electrocardiography, and cardiographic monitoring for ≥24âhours revealed no AF, indicating a probable diagnosis of artery-to-artery embolism following left common carotid artery stenosis detected by carotid ultrasound imaging and cerebral angiography. INTERVENTIONS: However, because of high blood brain natriuretic peptide (BNP) and valvular heart disease, continuous monitoring using Duranta was performed from the 2nd to 13th days after onset to exclude possible cardioembolic stroke. Waveform and heart rate trend graph analysis showed paroxysmal AF (PAF) occurred on the 5th and 9th days after onset. PAF did not occur at any other time during the observation period. The quality of the cardiograms sufficed for analysis and diagnosis of AF. The lightweight compact device can be placed quickly with no movement restriction. These features and our findings show the usefulness of the Duranta device for long-term continuous monitoring. LESSONS: A noninvasive wireless patch-type electrocardiographic monitoring system, Duranta, placed at the precordium, was useful in detecting covert AF in cryptogenic stroke patients, warranting further investigation.