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Intravenous acetaminophen is an integral component of multimodal postoperative pain management. This prospective study aims to assess the efficacy of the repeated administration of intravenous acetaminophen and the impact on postoperative patient satisfaction with postoperative pain management after total knee arthroplasty (TKA). We enrolled 98 patients scheduled for unilateral TKA. Patients were randomly assigned to receive either 1000 mg of intravenous acetaminophen at 6-hour intervals (AAP group) or not to receive intravenous acetaminophen (control group). All patients underwent single-shot femoral nerve block after general anesthesia, as well as intraoperative periarticular infiltration of analgesia prior to implantation. The primary outcome was the postoperative numerical rating scale (NRS) pain score at rest. The NRS score was measured just before the administration of study drugs, immediately after arrival in the ward (time 0), and at 6, 12, 18, 24, and 48 h (time 1 to time 5, respectively) postoperatively. We also evaluated the mean doses of rescue opioid use for 24 h postoperatively. At time 5, the AAP group had significantly improved mean NRS score than controls (3.0 vs. 4.0; P < 0.01). Rescue opioid use was significantly lower in the AAP group for 24 hours compared to controls (0.3 µg vs. 0.9 µg; P < 0.01). Repeated intravenous acetaminophen administration after TKA may provide better analgesia and reduce opioid use.
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Acetaminofén , Artroplastia de Reemplazo de Rodilla , Humanos , Acetaminofén/uso terapéutico , Manejo del Dolor , Artroplastia de Reemplazo de Rodilla/efectos adversos , Analgésicos Opioides/uso terapéutico , Estudios Prospectivos , Dolor Postoperatorio/tratamiento farmacológicoRESUMEN
The KamLAND-Zen experiment has provided stringent constraints on the neutrinoless double-beta (0νßß) decay half-life in ^{136}Xe using a xenon-loaded liquid scintillator. We report an improved search using an upgraded detector with almost double the amount of xenon and an ultralow radioactivity container, corresponding to an exposure of 970 kg yr of ^{136}Xe. These new data provide valuable insight into backgrounds, especially from cosmic muon spallation of xenon, and have required the use of novel background rejection techniques. We obtain a lower limit for the 0νßß decay half-life of T_{1/2}^{0ν}>2.3×10^{26} yr at 90% C.L., corresponding to upper limits on the effective Majorana neutrino mass of 36-156 meV using commonly adopted nuclear matrix element calculations.
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OBJECTIVES: We aimed to examine the association of muscle evaluation, including muscle ultrasound, with hospital-associated disability (HAD), focusing on ADL categories. DESIGN: A prospective observational cohort study. SETTING AND PARTICIPANTS: We recruited patients aged 65 years or older who were admitted to the geriatric ward of an acute hospital between October 2019 and September 2021. MEASUREMENTS: Handgrip strength, bioimpedance analyzer-determined skeletal muscle mass, bilateral thigh muscle thickness (BATT), and the echo intensity of the rectus femoris on muscle ultrasound were performed as muscle assessments. HAD was evaluated separately for mobility impairments and self-care impairments. RESULTS: In total, 256 individuals (mean age, 85.2 years; male sex, 41.8%) were analyzed. HAD in mobility was more common than HAD in self-care (37.5% vs. 30.0%). Only BATT was independently associated with HAD in mobility in multiple logistic regression analysis. There was no significant association between muscle indicators and HAD in self-care. CONCLUSION: A lower BATT was associated with a higher prevalence of HAD in mobility, suggesting the need to reconsider muscle assessment methods in hospitalized older adults. In addition, approaches other than physical may be required, such as psychosocial and environmental interventions to improve HAD in self-care.
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Sarcopenia , Anciano , Anciano de 80 o más Años , Evaluación de la Discapacidad , Fuerza de la Mano , Hospitales , Humanos , Masculino , Fuerza Muscular/fisiología , Músculo Esquelético/diagnóstico por imagen , Estudios Prospectivos , Sarcopenia/epidemiologíaRESUMEN
OBJECTIVE: We have previously reported the novel off-target microtubules destabilizing activity of SB225002, a compound that was originally designed as a selective and potent IL-8 receptor B antagonist. In the present study we investigated the reversibility of SB225002 antimitotic effect and provided additional mechanistic insights underlying cell death induction in SW480 human colorectal adenocarcinoma cells. MATERIALS AND METHODS: Mitotically arrested cells by SB225002 treatment were isolated by shake-off, and their identity was verified by both flow cytometry and immunoblotting. The reversibility of SB225002 antimitotic effects was investigated by flow cytometry and immunoblotting. Prometaphase arrested cells were imaged via indirect immunofluorescence and confocal microscopy. Activation of CHK1 in mitotically arrested cells was assessed by immunoblotting, and the relationship between CHK1 and mitotic arrest was examined via siRNA-mediated knockdown of CHK1. JNK signaling was evaluated via immunoblotting as well as pharmacological inhibition, followed by flow cytometry. The role of reactive oxygen species (ROS) in cytotoxicity was evaluated by ROS scavenging and flow cytometry. RESULTS: Following SB225002 washout, the mitotic checkpoint was abrogated, and cell cycle perturbations were gradually restored with induction of cell death. Mechanistically, CHK1 checkpoint was activated by SB225002 and occurred downstream of the mitotic checkpoint. In addition, SB225002 activated JNK signaling which contributed to cell death and restrained polyploidy. Furthermore, SB225002 increased intracellular ROS which played a role in mediating SB225002 cytotoxicity. CONCLUSIONS: Findings of the present study warrants further development of SB225002 as a lead compound that uniquely targets microtubules dynamics and IL-8 signaling.
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Antimitóticos , Compuestos de Fenilurea , Receptores de Interleucina-8 , Humanos , Microtúbulos , Compuestos de Fenilurea/farmacología , Especies Reactivas de Oxígeno , Receptores de Interleucina-8/antagonistas & inhibidoresRESUMEN
High flexural strength of computer-aided manufacturing resin composite blocks (CAD/CAM RCBs) are required in clinical scenarios. However, the conventional in vitro approach of modifying materials' composition by trial and error was not efficient to explore the effective components that contribute to the flexural strength. Machine learning (ML) is a powerful tool to achieve the above goals. Therefore, the aim of this study was to develop ML models to predict the flexural strength of CAD/CAM RCBs and explore the components that affect flexural strength as the first step. The composition of 12 commercially available products and flexural strength were collected from the manufacturers and literature. The initial data consisted of 16 attributes and 12 samples. Considering that the input data for each sample were recognized as a multidimensional vector, a fluctuation range of 0.1 was proposed for each vector and the number of samples was augmented to 120. Regression algorithms-that is, random forest (RF), extra trees, gradient boosting decision tree, light gradient boosting machine, and extreme gradient boosting-were used to develop 5 ML models to predict flexural strength. An exhaustive search and feature importance analysis were conducted to analyze the effective components that affected flexural strength. The R2 values for each model were 0.947, 0.997, 0.998, 0.983, and 0.927, respectively. The relative errors of all the algorithms were within 15%. Among the high predicted flexural strength group in the exhaustive search, urethane dimethacrylate was contained in all compositions. Filler content and triethylene glycol dimethacrylate were the top 2 features predicted by all models in the feature importance analysis. ZrSiO4 was the third important feature for all models, except the RF model. The ML models established in this study successfully predicted the flexural strength of CAD/CAM RCBs and identified the effective components that affected flexural strength based on the available data set.
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Resinas Compuestas , Diseño Asistido por Computadora , Inteligencia Artificial , Cerámica , Ensayo de Materiales , Propiedades de SuperficieRESUMEN
OBJECTIVE: To quantify the spatial distributions of cartilage and subchondral bone thickness of the distal radius. DESIGN: Using 17 cadaveric wrists, three types of 3-dimensional models were created: a cartilage-bone model, obtained by laser scanning; a bone model, rescanned after dissolving the cartilage; and a subchondral bone model, obtained using computed tomography. By superimposing the bone model onto the cartilage-bone and the subchondral bone models, the cartilage and subchondral bone thickness were determined. Measurements along with the spatial distribution were made at fixed anatomic points including the scaphoid and lunate fossa, sigmoid notch and interfossal ridge, and compared at each of these four regions. RESULTS: Cartilage thickness of the interfossal ridge (0.89 ± 0.23 mm) had a larger average thickness compared to that of the scaphoid fossa (0.70 ± 0.18 mm; p = 0.004), lunate fossa (0.75 ± 0.17 mm; p = 0.044) and sigmoid notch (0.64 ± 0.13 mm; p < 0.001). Subchondral bone was found to be thickest at the scaphoid (2.18 ± 0.72 mm) and lunate fossae (1.94 ± 0.93 mm), which were both thicker than that of sigmoid notch (1.63 ± 1.06 mm: vs scaphoid fossa, p = 0.020) or interfossal ridge (1.54 ± 0.84 mm: vs scaphoid fossa, p = 0.004; vs lunate fossa, p = 0.048). In the volar-ulnar sub-regions of the scaphoid and lunate fossa, the subchondral bone thickened. CONCLUSIONS: Our data can be applied when treating distal radius fractures. Cartilage thickness was less than 1 mm across the articular surface, which may give an insight into threshold for an acceptable range of step-offs. The combined findings of subchondral bone appreciate the importance of the volar-ulnar corner of the distal radius in the volar locking plate fixation.
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Cartílago Articular/anatomía & histología , Radio (Anatomía)/anatomía & histología , Articulación de la Muñeca/anatomía & histología , Anciano , Anciano de 80 o más Años , Cadáver , Cartílago Articular/diagnóstico por imagen , Simulación por Computador , Femenino , Humanos , Imagenología Tridimensional , Masculino , Radio (Anatomía)/diagnóstico por imagen , Tomografía Computarizada Espiral , Articulación de la Muñeca/diagnóstico por imagenRESUMEN
OBJECTIVE: To investigate olfactory function in elderly subjects requiring nursing care to clarify its association with appetite and nutritional status. SETTING: Facility for the elderly requiring nursing care. PARTICIPANTS: The subjects were 158 elderly people requiring nursing care and 37 elderly people not requiring nursing care. MEASUREMENTS: Experiment I: Olfactory function and factors (cognitive function, appetite, and nutritional status) that may be associated with it were compared between the elderly subjects requiring nursing care and those not requiring nursing care using covariance analysis in consideration of age. For evaluation, the OSIT-J was used for olfactory function, the HDS-R for cognitive function, the CNAQ for appetite, and BMI for nutritional status. Experiment II: The subjects were the same elderly subjects requiring nursing care in Experiment I, and food intake was surveyed in addition to the OSIT-J, HDS-R, CNAQ, and BMI. A univariate linear regression analysis was performed with OSIT-J as the response variable, and age, HDS-R, CNAQ, BMI, and food intake as the explanatory variables. RESULTS: Experiment I: On covariance analysis, the OSIT-J score was significantly lower for the elderly subjects requiring nursing care than for those not requiring nursing care (p<0.01). The mean score was 8 or lower in both groups, demonstrating lower olfactory function in both groups. Regarding factors that may be associated with olfactory function, a significant difference was noted in the HDS-R (p<0.01), confirming significantly lower cognitive function in the elderly subjects requiring nursing care. No significant difference was noted in the CNAQ or BMI. Experiment II: On a univariate linear regression analysis, an association with the OSIT-J was noted for age and HDS-R. Age was inversely correlated and the HDS-R was positively correlated. Factors associated with lower olfactory function in the elderly subjects requiring nursing were age and cognitive function, whereas appetite, nutritional status, and food intake were not associated. CONCLUSION: Olfactory function in elderly subjects requiring nursing care was poorer than that in those not requiring nursing care, suggesting that aging and cognitive decline are associated with lower olfactory function. In addition, no association of lower olfactory function with appetite, nutritional status, or food intake was noted in the elderly subjects requiring nursing care.
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Apetito/fisiología , Enfermería Geriátrica/normas , Estado Nutricional/fisiología , Olfato/fisiología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , MasculinoRESUMEN
Sugammadex is a novel reversal agent for aminosteroid neuromuscular blocking drugs, especially rocuronium. Given its renal excretion, sugammadex is not recommended for patients with end-stage renal disease; however, reports exist of its use in this group of patients. This two-institutional retrospective observational study aimed to review the safety profile and effectiveness of sugammadex in surgical patients with end-stage renal disease who required pre-operative renal replacement therapy. Adult surgical patients with end-stage renal disease requiring pre-operative renal replacement therapy, who received sugammadex between April 2016 and January 2019, were studied. The primary outcome was the incidence of postoperative tracheal re-intubation within 48 h. The secondary outcome was the incidence of deferred tracheal extubation in the operating theatre. One hundred and fifty-eight patients were identified from 125,653 surgical patients: 48 patients (30%) underwent renal transplantation and 110 (70%) underwent non-renal transplantation procedures. There were 22 instances (14%) of deferred tracheal extubation due to surgical and/or pre-existing medical conditions. Out of the 136 patients who had the tracheal tube removed at the end of the procedure, three patients had their trachea re-intubated within 48 h: two patients developed pulmonary oedema resulting from volume overload; and one patient had worsening sepsis. No incidence of recurrence of neuromuscular blockade was observed. Of note, 24 (18%) patients were found to have incomplete neuromuscular blockade reversal with neostigmine but administration of sugammadex led to successful tracheal extubation. In conclusion, sugammadex appears to be safe and effective in adult patients with end-stage renal disease receiving pre-operative renal replacement therapy.
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Fallo Renal Crónico/complicaciones , Sugammadex/efectos adversos , Sugammadex/uso terapéutico , Adulto , Anciano , Extubación Traqueal , Femenino , Humanos , Incidencia , Intubación Intratraqueal , Fallo Renal Crónico/fisiopatología , Trasplante de Riñón/métodos , Masculino , Persona de Mediana Edad , Bloqueo Neuromuscular , Complicaciones Posoperatorias/epidemiología , Cuidados Preoperatorios , Terapia de Reemplazo Renal , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: The present quantitative study aimed to assess the three-dimensional (3-D) cartilage wear patterns of the first metacarpal and trapezium in the advanced stage of osteoarthritis (OA) and compare cartilage measurements with radiographic severity. DESIGN: Using 19 cadaveric trapeziometacarpal (TMC) joints, 3-D cartilage surface models of the first metacarpal and trapezium were created with a laser scanner, and 3-D bone surface model counterparts were similarly created after dissolving the cartilage. These two models were superimposed, and the interval distance on the articular surface as the cartilage thickness was measured. All measurements were obtained in categorized anatomic regions on the articular surface of the respective bone, and we analyzed the 3-D wear patterns on the entire cartilage surface. Furthermore, we compared measurements of cartilage thickness with radiographic OA severity according to the Eaton grading system using Pearson correlation coefficients (r). RESULTS: In the first metacarpal, the cartilage thickness declined volarly (the mean cartilage thickness of the volar region was 0.32 ± 0.16 mm, whereas that of the dorsal region was 0.53 ± 0.18 mm). Conversely, the cartilage evenly degenerated throughout the articular surface of the trapezium. Measurements of the categorized regions where cartilage thinning was remarkable exhibited statistical correlations with radiographic staging (r = -0.48 to -0.72). CONCLUSIONS: Our findings indicate that cartilage wear patterns differ between the first metacarpal and trapezium in the late stage of OA. There is a need for further studies on cartilage degeneration leading to symptomatic OA in the TMC joint.
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Articulaciones Carpometacarpianas , Cartílago Articular , Simulación por Computador , Huesos del Metacarpo , Osteoartritis , Hueso Trapecio , Anciano , Anciano de 80 o más Años , Cadáver , Articulaciones Carpometacarpianas/diagnóstico por imagen , Articulaciones Carpometacarpianas/patología , Cartílago Articular/diagnóstico por imagen , Cartílago Articular/patología , Femenino , Humanos , Imagenología Tridimensional , Rayos Láser , Masculino , Huesos del Metacarpo/diagnóstico por imagen , Huesos del Metacarpo/patología , Osteoartritis/diagnóstico por imagen , Osteoartritis/patología , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X , Hueso Trapecio/diagnóstico por imagen , Hueso Trapecio/patologíaRESUMEN
AIMS: The aim of this study was to examine whether hips with unilateral osteoarthritis (OA) secondary to developmental dysplasia of the hip (DDH) have significant asymmetry in femoral length, and to determine potential related factors. PATIENTS AND METHODS: We enrolled 90 patients (82 female, eight male) with DDH showing unilateral OA changes, and 43 healthy volunteers (26 female, 17 male) as controls. The mean age was 61.8 years (39 to 93) for the DDH groups, and 71.2 years (57 to 84) for the control group. Using a CT-based coordinate measurement system, we evaluated the following vertical distances: top of the greater trochanter to the knee centre (femoral length GT), most medial prominence of the lesser trochanter to the knee centre (femoral length LT), and top of the greater trochanter to the medial prominence of the lesser trochanter (intertrochanteric distance), along with assessments of femoral neck anteversion and neck shaft angle. RESULTS: The percentages of hips with an absolute difference of > 5 mm in femoral GT and LT lengths were significantly larger in the DDH group (24% for both) compared with those of the control group (2% and 7%, respectively). The femoral length GT of the affected femur was significantly shorter in Crowe I and longer in Crowe IV than that of the unaffected side. The affected-to-unaffected difference of the intertrochanteric distance showed positive correlation with that of the femoral length GT in Crowe I and Crowe II/III, and negative correlation with that of the femoral length LT in the Crowe I and Crowe IV groups. CONCLUSION: Hips with unilateral end-stage OA secondary to DDH show significant asymmetry in femoral length between both the greater and lesser trochanter and the knee compared with controls. The intertrochanteric distance was a morphological factor related to femoral-length asymmetry. When undertaking total hip arthroplasty (THA) in the presence of DDH, long leg radiographs or CT measurements should be used to assess true leg-length discrepancy. Cite this article: Bone Joint J 2019;101-B:297-302.
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Fémur/diagnóstico por imagen , Luxación Congénita de la Cadera/cirugía , Diferencia de Longitud de las Piernas/diagnóstico por imagen , Osteoartritis de la Cadera/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Fémur/anomalías , Fémur/cirugía , Luxación Congénita de la Cadera/complicaciones , Luxación Congénita de la Cadera/diagnóstico por imagen , Humanos , Diferencia de Longitud de las Piernas/etiología , Diferencia de Longitud de las Piernas/cirugía , Masculino , Persona de Mediana Edad , Osteoartritis de la Cadera/diagnóstico por imagen , Osteoartritis de la Cadera/etiología , Tomografía Computarizada por Rayos XRESUMEN
This paper is an attempt to understand the coil splitting phenomena by means of fracture mechanics. The methods used combine the residual stress measurement with neutron and finite element analysis. The support of the metallurgical evaluation is used as evidence to justify the use of the fracture mechanics concept. Comparing coil springs manufactured at two different manufacturing lines, namely N1 and N6, residual stress distributions in three main directions were measured using neutron diffraction. The results of the residual stress measurement were then converted into the stress intensity factor to enable the analysis in fracture mechanics. The mixed-mode analysis of opening, Mode I, and in-plane shearing, Mode II, is used to solve the splitting problem. The discrepancy between the coil made at N1 and N6 was identified and taken into account in terms of the profile difference. Based on this difference, an FEA simulation was conducted. The results support the experimental finding, which is that the shape of the coil manufactured influences the pattern of the residual stress, which leads to different splitting behaviors. This simple analysis helps practitioners understand why, and how, some cold coiled products split after manufacturing. It is concluded that this very basic concept of fracture mechanics can be used to establish the limit of the cold coiling process by evaluation of the mixed-mode stress intensity factor to the fracture toughness of the material.
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Long-term follow-up of patients with adhesive capsulitis (AC) reveals that approximately half of them suffer from a limited range of shoulder motion, particularly external and/or internal rotation. We report the surgical technique and short-term clinical outcomes of ultrasound-guided release of the thickened coracohumeral (CH) ligament in 8 patients (9 shoulders) with AC. Passive external rotation with the arm by the side significantly increased from an average of 18° preoperatively to 47° immediately after CH ligament release. VAS and ASES scores were improved at 3months follow-up in all 9 shoulders, and maintained at 6months follow-up in 6 shoulders. No procedure-related adverse events developed over the 6-month follow-up period. Ultrasound-guided release for thickened CH ligament is a reliable and effective minimally invasive surgery for persistent limited external rotation due to AC of the shoulder.
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Bursitis/fisiopatología , Bursitis/cirugía , Ligamentos Articulares/diagnóstico por imagen , Ligamentos Articulares/cirugía , Articulación del Hombro/fisiopatología , Adulto , Anciano , Bursitis/complicaciones , Apófisis Coracoides , Femenino , Humanos , Húmero , Masculino , Persona de Mediana Edad , Rango del Movimiento Articular , Rotación , Articulación del Hombro/cirugía , Dolor de Hombro/etiología , Cirugía Asistida por Computador , UltrasonografíaRESUMEN
AIM: Stomach contractions show two types of specific patterns in many species, that is migrating motor contraction (MMC) and postprandial contractions (PPCs), in the fasting and fed states respectively. We found gastric PPCs terminated with migrating strong contractions in humans, dogs and suncus. In this study, we reveal the detailed characteristics and physiological implications of these strong contractions of PPC. METHODS: Human, suncus and canine gastric contractions were recorded with a motility-monitoring ingestible capsule and a strain-gauge force transducer. The response of motilin and ghrelin and its receptor antagonist on the contractions were studied by using free-moving suncus. RESULTS: Strong gastric contractions were observed at the end of a PPC in human, dog and suncus models, and we tentatively designated this contraction to be a postprandial giant contraction (PPGC). In the suncus, the PPGC showed the same property as those of a phase III contraction of MMC (PIII-MMC) in the duration, motility index and response to motilin or ghrelin antagonist administration. Ghrelin antagonist administration in the latter half of the PPC (LH-PPC) attenuated gastric contraction prolonged the duration of occurrence of PPGC, as found in PII-MMC. CONCLUSION: It is thought that the first half of the PPC changed to PII-MMC and then terminated with PIII-MMC, suggesting that PPC consists of a digestive phase (the first half of the PPC) and a discharge phase (LH-PPC) and that LH-PPC is coincident with MMC. In this study, we propose a new approach for the understanding of postprandial contractions.
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Motilidad Gastrointestinal/fisiología , Ghrelina/metabolismo , Motilina/metabolismo , Periodo Posprandial/fisiología , Musarañas/fisiología , Animales , Perros , Humanos , Contracción Muscular/fisiología , Estómago/fisiologíaRESUMEN
The expression of cyclin D1 is upregulated in various cancer cells by diverse mechanisms, such as increases in mRNA levels, the promotion of the translation by mammalian target of rapamycin complex 1 (mTORC1) signaling and the protein stabilization. We here show that sesaminol, a sesame lignan, reduces the expression of cyclin D1 with decreasing mRNA expression levels, inhibiting mTORC1 signaling and promoting proteasomal degradation. We subsequently generated sesaminol-immobilized FG beads to newly identify sesaminol-binding proteins. As a consequence, we found that adenine nucleotide translocase 2 (ANT2), the inner mitochondrial membrane protein, directly bound to sesaminol. Consistent with the effects of sesaminol, the depletion of ANT2 caused a reduction in cyclin D1 with decreases in its mRNA levels, mTORC1 inhibition and the proteasomal degradation of its protein, suggesting that sesaminol negatively regulates the function of ANT2. Furthermore, we screened other ANT2-binding compounds and found that the proliferator-activated receptor-γ agonist troglitazone also reduced cyclin D1 expression in a multifaceted manner, analogous to that of the sesaminol treatment and ANT2 depletion. Therefore, the chemical biology approach using magnetic FG beads employed in the present study revealed that sesaminol bound to ANT2, which may pleiotropically upregulate cyclin D1 expression at the mRNA level and protein level with mTORC1 activation and protein stabilization. These results suggest the potential of ANT2 as a target against cyclin D1-overexpressing cancers.
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Papillary thyroid carcinoma (PTC), the most frequent thyroid cancer, is characterized by low proliferation but no apoptosis, presenting frequent lymph-node metastasis. Papillary thyroid carcinoma overexpress transforming growth factor-beta (TGF-ß). In human cells, TGF-ß has two opposing actions: antitumoral through pro-apoptotic and cytostatic activities, and pro-tumoral promoting growth and metastasis. The switch converting TGF-ß from a tumor-suppressor to tumor-promoter has not been identified. In the current study, we have quantified a parallel upregulation of TGF-ß and nuclear p27, a CDK2 inhibitor, in samples from PTC. We established primary cultures from follicular epithelium in human homeostatic conditions (h7H medium). TGF-ß-dependent cytostasis occurred in normal and cancer cells through p15/CDKN2B induction. However, TGF-ß induced apoptosis in normal and benign but not in carcinoma cultures. In normal thyroid cells, TGF-ß/SMAD repressed the p27/CDKN1B gene, activating CDK2-dependent SMAD3 phosphorylation to induce p50 NFκB-dependent BAX upregulation and apoptosis. In thyroid cancer cells, oncogene activation prevented TGF-ß/SMAD-dependent p27 repression, and CDK2/SMAD3 phosphorylation, leading to p65 NFκB upregulation which repressed BAX, induced cyclin D1 and promoted TGF-ß-dependent growth. In PTC samples from patients, upregulation of TGF-ß, p27, p65 and cyclin D1 mRNA were significantly correlated, while the expression of the isoform BAX-ß, exclusively transcribed in apoptotic cells, was negatively correlated. Additionally, combined ERK and p65 NFκB inhibitors reduced p27 expression and potentiated apoptosis in thyroid cancer cells while not affecting survival in normal thyroid cells. Our results therefore suggest that the oncoprotein p27 reorganizes the effects of TGF-ß in thyroid cancer, explaining the slow proliferation but lack of apoptosis and metastatic behavior of PTC.
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Carcinoma/genética , Carcinoma/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/genética , FN-kappa B/metabolismo , Proteínas Smad/metabolismo , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Apoptosis/fisiología , Carcinoma/patología , Carcinoma Papilar , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Humanos , Transducción de Señal , Proteína smad3/metabolismo , Proteína Smad4/metabolismo , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/patología , TransfecciónRESUMEN
In several studies of patients with type 2 diabetes mellitus, a positive association between depressive symptoms and erectile dysfunction (ED) has been reported. No evidence exists, however, regarding the association between depressive symptoms and ED among Japanese patients with type 2 diabetes mellitus. Thus, we examined this issue among Japanese patients with type 2 diabetes mellitus. Study subjects were 469 male Japanese patients with type 2 diabetes mellitus, aged 19 years or over. ED, moderate to severe ED and severe ED were defined as present when a subject had a Sexual Health Inventory for Men score <22, <12 and <8, respectively. Depressive symptoms were defined as present when a subject had a Self-Rating Depression Scale (SDS) score >49. Adjustment was made for age, body mass index, waist, duration of type 2 diabetes, current smoking, current drinking, hypertension, dyslipidemia, coronary artery disease, stroke, glycated hemoglobin and diabetic neuropathy. The prevalence values of depressive symptoms, moderate to severe ED and severe ED were 15.1%, 64.2% and 51.0%, respectively. Depressive symptoms were independently positively associated with moderate to severe ED and severe ED (adjusted odds ratios were 2.23 (95% confidence interval (CI): 1.17-4.43) and 1.86 (95% CI: 1.04-3.41), respectively). In Japanese patients with type 2 diabetes mellitus, depressive symptoms may be associated with ED.
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Depresión/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Disfunción Eréctil/epidemiología , Disfunción Eréctil/psicología , Anciano , Humanos , Japón , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Escalas de Valoración Psiquiátrica , Factores de Riesgo , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
Only limited epidemiological evidence exists regarding the relationship between diabetic neuropathy and erectile dysfunction (ED) among Japanese patients with type 2 diabetes mellitus. To investigate the relationship between diabetic neuropathy and ED among Japanese patients with type 2 diabetes mellitus, a multicenter cross-sectional study was conducted in 287 male Japanese patients with type 2 diabetes mellitus, age (19-65 years). Diabetic neuropathy was diagnosed if the patients showed two or more of the following three characteristics: neuropathic symptoms, decreased or disappeared Achilles tendon reflex and/or abnormal vibration perception. ED, moderate to severe ED, and severe ED were defined as present when a subject had a Sexual Health Inventory for Men score <22, <12 and <8, respectively. The prevalence values of diabetic neuropathy and severe ED were 47.0 and 39.0%, respectively. Diabetic neuropathy was independently positively associated with severe ED, but not ED and moderate ED: the adjusted odds ratio was 1.90 (95% confidence interval: 1.08-3.38). No relationships were found between diabetic retinopathy or diabetic nephropathy and ED. Diabetic neuropathy is positively associated with severe erectile dysfunction among Japanese type 2 diabetes mellitus patients aged <65 years.