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BACKGROUND: In walking in healthy adults, rotation of the hip joint affects stride length and shifts the center of gravity, but these are not seen in hip osteoarthritis which affects gait. In gait of total hip arthroplasty, there are few reports on changes in the horizontal plane. This study clarified the preoperative and early postoperative gait characteristics of patients undergoing total hip arthroplasty. METHODS: The analysis included 12 females who underwent initial total hip arthroplasty using a posterolateral approach. Gait was measured pre and postoperatively using a three-dimensional motion analysis device. Statistics were compared pre and postoperative range of motion, muscle strength, walking speed, stride length, gravity movement distance, trunk angle, hip joint angle, and joint moment. FINDINGS: The maximum hip abduction moment and trunk flexion angle to the surgical side were lower than in healthy subjects. The angle of internal rotation during the stance phase was significantly higher in the postoperative period. The distance of the center of gravity shift in the left and right directions was significantly decreased postoperatively. INTERPRETATION: Gait disturbance was seen preoperatively and remained after surgery. Walking after total hip arthroplasty provides the hip joint rotates inward which is closer to normal walking. However, no change was observed in the external rotation moment of the hip joint during walking. We suspect that the invasiveness of the posterolateral approach of total hip arthroplasty affects the muscles for external rotation of the hip joint. This can also cause in gait disturbances.
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In recent decades, taste sensors have been increasingly utilized to assess the taste of oral medicines, particularly focusing on bitterness, a major obstacle to patient acceptance and adherence. This objective and safe method holds promise for enhancing the development of patient-friendly medicines in pharmaceutical companies. This review article introduces its application in measuring the intensity of bitterness in medicine, confirming the achievement of taste masking, distinguishing taste differences between branded and generic medicines, and identifying substances to suppress bitterness in target medicines. Another application of the sensor is to predict a significant increase in bitterness when medicine is taken with certain foods/beverages or concomitant medication. Additionally, to verify the sensor's predictability, a significant correlation has been demonstrated between the output of a bitter-sensitive sensor designed for drug bitterness (BT0) and the bitterness responses of the human taste receptor hT2R14 from BitterDB (huji.ac.il). As a recent advancement, a novel taste sensor equipped with lipid/polymer membranes modified by 3-Br-2,6-dihydroxybenzoic acid (2,6-DHBA), based on the concept of allostery, is introduced. This sensor successfully predicts the bitterness of non-charged pharmaceuticals with xanthine skeletons, such as caffeine or related compounds. Finally, the future prospects of taste sensors are discussed.
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Técnicas Biosensibles , Gusto , Humanos , Gusto/fisiología , Gusto/efectos de los fármacos , Técnicas Biosensibles/métodos , Técnicas Biosensibles/instrumentación , Receptores Acoplados a Proteínas G/metabolismo , Preparaciones Farmacéuticas/análisisRESUMEN
Taste sensors with an allostery approach have been studied to detect non-charged bitter substances, such as xanthine derivatives, used in foods (e.g., caffeine) or pharmaceuticals (e.g., etofylline). In this study, the authors modified a taste sensor with 3-bromo-2,6-dihydroxybenzoic acid and used it in conjunction with sensory tests to assess the bitterness of non-charged pharmaceuticals with xanthine scaffolds (i.e., acefylline and doxofylline), as well as allopurinol, an analogue of hypoxanthine. The results show that the sensor was able to differentiate between different levels of sample bitterness. For instance, when assessing a 30 mM sample solution, the sensor response to acefylline was 34.24 mV, which corresponded to the highest level of bitterness (τ = 3.50), while the response to allopurinol was lowest at 2.72 mV, corresponding to relatively weaker bitterness (τ = 0.50). Additionally, this study extended the application of the sensor to detect pentoxifylline, an active pharmaceutical ingredient in pediatric medicines. These results underscore the taste sensor's value as an additional tool for early-stage assessment and prediction of bitterness in non-charged pharmaceuticals.
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Alopurinol , Gusto , Xantina , Alopurinol/química , Humanos , Xantina/química , Técnicas Biosensibles/métodosRESUMEN
Following the discovery of podocyte phospholipase A2 receptor and thrombospondin type-1 domain-containing 7A, various potential target antigens for membranous nephropathy (MN) have been reported one after another. MN target antigens have now been identified in a significant proportion of patients, and a new classification framework classifies patients with MN based on the detected antigen and associated disease phenotype. A serology-based approach that does not require a histological diagnosis for patients suspected of having MN has also been proposed. However, there have been cases in which dual positivity for MN antigens and/or corresponding antibodies has been shown. Importantly, some of them showed a transition of the affected patient's immune responses to MN antigens, suggesting that serological diagnosis changes depending on the timing of the analysis. In this review, we provide detailed information on these cases and present an overview of our recent understanding of their putative mechanisms involved in these cases. Greater awareness is required to adequately recognize and develop appropriate therapeutic strategies for this condition.
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Glomerulonefritis Membranosa , Glomerulonefritis Membranosa/inmunología , Glomerulonefritis Membranosa/diagnóstico , Glomerulonefritis Membranosa/sangre , Humanos , Receptores de Fosfolipasa A2/inmunología , Receptores de Fosfolipasa A2/metabolismo , Autoantígenos/inmunología , Prevalencia , Podocitos/metabolismo , Podocitos/inmunología , Podocitos/patología , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Trombospondinas/inmunología , Trombospondinas/metabolismoRESUMEN
BACKGROUND: No comprehensive analysis of the pulmonary sequelae of coronavirus disease 2019 (COVID-19) in Japan based on respiratory function tests and chest computed tomography (CT) has been reported. We evaluated post-COVID-19 conditions, especially focusing on pulmonary sequelae assessed by pulmonary function tests and chest CT. METHODS: For this prospective cohort study, we enrolled 1069 patients who presented pneumonia at the time of admission in 55 hospitals from February 2020 to September 2021. Disease severity was classified as moderateâ , moderate II, and severe, defined primarily according to the degree of respiratory failure. The data on post-COVID-19 conditions over 12 months, pulmonary function, and chest CT findings at 3 months were evaluated in this study. Additionally, the impact of COVID-19 severity on pulmonary sequelae, such as impaired diffusion capacity, restrictive pattern, and CT abnormalities, was also evaluated. RESULTS: The most frequently reported post-COVID-19 conditions at 3 months after COVID-19 were muscle weakness, dyspnea, and fatigue (48.4%, 29.0%, and 24.7%, respectively). The frequency of symptoms gradually decreased over subsequent months. In pulmonary function tests at 3 months, the incidence of impaired diffusion capacity and restrictive pattern increased depending on disease severity. There also were differences in the presence of chest CT abnormalities at the 3 months, which was markedly correlated with the severity. CONCLUSION: We reported a comprehensive analysis of post-COVID-19 condition, pulmonary function, and chest CT abnormalities in Japanese patients with COVID-19. The findings of this study will serve as valuable reference data for future post-COVID-19 condition research in Japan.
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COVID-19 , Pulmón , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios de Cohortes , COVID-19/complicaciones , COVID-19/diagnóstico por imagen , COVID-19/epidemiología , Disnea/etiología , Pueblos del Este de Asia , Japón/epidemiología , Pulmón/diagnóstico por imagen , Pulmón/fisiopatología , Alta del Paciente , Estudios Prospectivos , Pruebas de Función Respiratoria , Índice de Severidad de la Enfermedad , Sociedades Médicas , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
Hemophagocytic syndrome/macrophage activation syndrome (HPS/MAS) is a serious clinical condition that frequently leads to multiple organ failure, including acute kidney injury (AKI). Although the pathogenesis of AKI is not yet fully understood, it is believed to result from uncontrolled activation of the immune system involving macrophages and cytotoxic lymphocytes. Renal histology in HPS/MAS often presents with characteristic foamy glomerular lesions (glomerular lipidosis) with massive macrophage infiltration, known as histiocytic glomerulopathy. In this review, we introduce the recently proposed concept of renal-limited HPS/MAS as a novel etiology of histiocytic glomerular lipidosis. Patients with renal-limited HPS/MAS often develop AKI but do not fulfill the diagnostic criteria for HPS/MAS because their systemic manifestations are less severe. Therefore, the diagnosis largely depends on characteristic histological findings, that is, diffuse and global glomerular accumulation of foamy macrophages and cytotoxic lymphocytes accompanied by the interaction of these cells as well as the exclusion of various differential diseases. Although there are no established therapeutic regimens, these patients receive various types of therapies, including high-dose glucocorticoids, immunosuppressants, or anti-interleukin-1 drug, and generally achieve favorable outcomes. We summarized the concept, diagnostic challenges, and recent topics of this disease entity and discussed treatment options based on our own experiences.
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Renal biopsy is the gold standard for making the final diagnosis and for predicting the progression of renal disease, but monitoring disease status by performing biopsies repeatedly is impossible because it is an invasive procedure. Urine tests are non-invasive and may reflect the general condition of the whole kidney better than renal biopsy results. We therefore investigated the diagnostic value of extensive urinary sediment analysis by immunofluorescence staining for markers expressed on kidney-derived cells (cytokeratin: marker for tubular epithelial cells, synaptopodin: marker for podocytes, claudin1: marker for parietal epithelial cells, CD68: marker for macrophages (MΦ), neutrophil elastase: marker for neutrophils). We further examined the expression levels of the mRNAs for these markers by real-time reverse transcription polymerase chain reaction. We also examined the levels of mRNAs associated with the M1 (iNOS, IL-6) and M2 (CD163, CD204, CD206, IL-10) MΦ phenotypes. Evaluated markers were compared with clinical and histological findings for the assessment of renal diseases. Claudin1- and CD68-positive cell counts in urinary sediments were higher in patients with glomerular crescents (especially cellular crescents) than in patients without crescents. The relative levels of mRNA for CD68 and the M2 MΦ markers (CD163, CD204, CD206, and IL-10) in urinary sediments were also higher in patients with glomerular crescents. These data suggest that immunofluorescence staining for claudin1 and CD68 in urinary sediments and the relative levels of mRNA for CD68 and M2 MΦ markers in urinary sediments are useful for evaluating the state of glomerular diseases.
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Enfermedades Renales , Sistema Urinario , Humanos , Interleucina-10 , Riñón , Técnica del Anticuerpo FluorescenteAsunto(s)
Alérgenos , Rinitis Alérgica , Humanos , Desensibilización Inmunológica , Inmunidad , InmunoterapiaRESUMEN
BACKGROUND: Glomerular lipidosis is a rare histological feature presenting the extensive glomerular accumulation of lipids with or without histiocytic infiltration, which develops under various conditions. Among its various etiologies, macrophage activation syndrome (MAS) is a condition reported to be associated with histiocytic glomerular lipidosis. Here we describe the first case of glomerular lipidosis observed in a renal allograft that histologically mimicked histiocytic glomerulopathy owing to MAS. CASE PRESENTATION: A 42-year-old man underwent successful living-donor kidney transplantation. However, middle-grade proteinuria and increased serum triglyceride levels indicative of type V hyperlipidemia developed rapidly thereafter. An allograft biopsy performed 6 months after the transplantation showed extensive glomerular infiltration of CD68+ foam cells (histiocytes) intermingled with many CD3+ T-cells (predominantly CD8+ cells). Furthermore, frequent contact between glomerular T-cells and histiocytes, and the existence of activated CD8+ cells (CD8+, HLA-DR+ cells) were observed by double immunostaining. There was no clinicopathological data suggesting lipoprotein glomerulopathy or lecithin cholesterol acyltransferase deficiency, both of which are well-known causes of glomerular lipidosis. The histological findings were relatively similar to those of histiocytic glomerulopathy caused by MAS. As systemic manifestations of MAS, such as fever, pancytopenia, coagulation abnormalities, hyperferritinemia, increased liver enzyme levels, hepatosplenomegaly, and lymphadenopathy were minimal, this patient was clinicopathologically diagnosed as having renal-limited MAS. Although optimal treatment strategies for MAS in kidney transplant patients remains unclear, we strengthened lipid-lowering therapy using pemafibrate, without modifying the amount of immunosuppressants. Serum triglyceride levels were normalized with this treatment; however, the patient's extensive proteinuria and renal dysfunction did not improve. Biopsy analysis at 1 year after the transplantation demonstrated the disappearance of glomerular foamy changes, but the number of glomerular infiltrating cells remained similar. CONCLUSION: To our knowledge, this is the first reported case of glomerular lipidosis in a transplanted kidney. Increased interaction-activation of histiocytes (macrophages) and CD8+ T-cells, the key pathogenic feature of MAS, was observed in the glomeruli of this patient, who did not demonstrate overt systemic manifestations, suggesting a pathological condition of renal-limited MAS. The clinical effects of triglyceride-lowering therapy were limited, suggesting that hypertriglyceridemia was not the cause of but rather may be a consequence of renal-limited MAS.
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Enfermedades Renales , Trasplante de Riñón , Lipidosis , Síndrome de Activación Macrofágica , Masculino , Humanos , Adulto , Síndrome de Activación Macrofágica/etiología , Síndrome de Activación Macrofágica/complicaciones , Trasplante de Riñón/efectos adversos , Linfocitos T CD8-positivos , Riñón/patología , Enfermedades Renales/patología , Proteinuria/complicaciones , TriglicéridosRESUMEN
RATIONALE: Reports have suggested a relationship between coronavirus disease 2019 (COVID-19) vaccination and new-onset or recurring renal diseases, of which immunoglobulin A (IgA) nephropathy is a representative disease. Alveolar hemorrhage in patients with IgA nephropathy is rare but reportedly has a high mortality and morbidity. To our knowledge, there have been no reports regarding the development of IgA nephropathy with alveolar hemorrhage following COVID-19 vaccination. PATIENTS CONCERN: A 23-year-old Japanese man presented with hemoptysis and peripheral edema a few days after receiving a second dose of a COVID-19 mRNA vaccine. Severe renal failure and alveolar hemorrhage were noted thereafter, and renal biopsy showed crescentic glomerulonephritis with mesangial proliferation accompanied by mesangial electron-dense deposits containing IgA. Renal biopsy tissue also showed chronic histological changes suggestive of acute exacerbation of preexisting IgA nephropathy. DIAGNOSIS: The diagnosis of IgA nephropathy complicated by alveolar hemorrhage was made. INTERVENTIONS AND OUTCOMES: Renal function did not recover despite treatment with high-dose steroids; the patient was maintained on hemodialysis and eventually underwent successful renal transplantation. LESSONS: The present case suggested that although extremely rare, severe renal failure requiring renal replacement therapy could occur in patients with IgA nephropathy after COVID-19 vaccination. Future accumulation of similar cases is needed to predict the risk of renal injury following vaccination.
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Vacunas contra la COVID-19 , Glomerulonefritis por IGA , Humanos , Masculino , Adulto Joven , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Glomerulonefritis por IGA/patología , Hemorragia/complicaciones , Inmunoglobulina A/efectos adversos , Insuficiencia Renal/complicacionesRESUMEN
RATIONALE: A predominant Th2 immune response is suggested in the pathogenesis of both minimal change disease (MCD) and membranous nephropathy (MN); however, consecutive development of the 2 diseases in a patient is extremely rare. PATIENT CONCERN: A Japanese man, who developed nephrotic syndrome in his 50s and was diagnosed with MCD by renal biopsy, experienced a relapse of proteinuria approximately 3 years later during long-term steroid treatment. Since the proteinuria was resistant to increase in steroid dosage, repeat renal biopsy was performed, which revealed a small amount of glomerular subepithelial immune deposits containing immunoglobulin (Ig)G (dominantly IgG4). Immunostaining for thrombospondin-type-1-domain-containing-7A (THSD7A) was positive on the glomerular capillary walls, whereas that for other causative antigens of MN, such as phospholipase A2 receptor or neural epidermal growth factor-like 1 protein, was negative. Detailed examination found no associated condition, including malignancies and allergic diseases. DIAGNOSIS: The diagnosis of THSD7A-associated idiopathic MN was made. INTERVENTIONS AND OUTCOMES: He received further increased dose of steroids. Thereafter he maintained clinical improvement because his urinary protein level was decreased. LESSONS: The present case suggested that histological transition from MCD to MN is possible and repeat biopsy would be crucial for accurate diagnosis.
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Glomerulonefritis Membranosa , Nefrosis Lipoidea , Masculino , Humanos , Nefrosis Lipoidea/inducido químicamente , Nefrosis Lipoidea/tratamiento farmacológico , Nefrosis Lipoidea/patología , Glomérulos Renales/patología , Proteinuria/patología , Inmunoglobulina G , Esteroides , Autoanticuerpos , Receptores de Fosfolipasa A2RESUMEN
Although experimental models have shown that the innate immune system is a main contributor to acute kidney injury (AKI), its involvement in human sepsis-associated AKI (SA-AKI) remains unclear. We retrospectively evaluated 19 patients with SA-AKI who were treated with continuous renal replacement therapy (CRRT). Serum cytokine, complement components, and the proportion and functions of innate immune cells, such as CD56+ T cells, CD56+ natural killer (NK) cells, and monocytes, were analyzed. There were no differences in the proportions of CD56+ T and NK cells between patients with SA-AKI and healthy controls. In patients with SA-AKI, fas ligand (FasL) expression in CD56+ T cells was significantly upregulated, and the proportion of perforin-positive CD56+ T cells tended to be higher than that in healthy controls. The positive rate of both FasL and perforin of CD56+ T cells was significantly higher than that of CD56- T cells, which include cytotoxic T cells. Antigen-presenting capacity and phagocytic activity of monocytes in patients with SA-AKI were significantly decreased compared to those of healthy controls and did not recover soon after the initiation of CRRT. CD56+ T cells are involved in the disease processes of human SA-AKI through effector molecules such as FasL or perforin.
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Lesión Renal Aguda , Sepsis , Humanos , Perforina/metabolismo , Estudios Retrospectivos , Células Asesinas Naturales , Sepsis/complicaciones , Sepsis/metabolismo , Lesión Renal Aguda/metabolismoRESUMEN
Itraconazole, a commonly used antifungal drug in the clinic approved by U.S. Food and Drug Administration (FDA), has been gradually found to have anti-tumor, angiogenesis inhibition and other pharmacological activities. However, its poor water solubility and potential toxicity limited its clinical application. In order to improve the water solubility and reduce the side effects caused by the high concentration of itraconazole, a novel preparation method of itraconazole sustained release microspheres was established in this study. Firstly, five kinds of polylactic acid-glycolic acid (PLGA) microspheres loaded with itraconazole were prepared by oil/water (O/W) emulsion solvent evaporation and then characterized by infrared spectroscopy. Then the particle size and morphology of the microspheres were observed by scanning electron microscope (SEM) and transmission electron microscope (TEM). After that, the particle size distribution, drug loading rate, entrapment efficiency, and drug release experiments were evaluated. Our results showed the microspheres prepared in this study had uniform particle size distribution and good integrity. Further study found that the average drug loading of the five kinds of microspheres prepared with PLGA 7505, PLGA 7510, PLGA 7520, PLGA 5020 and PLGA 0020 were 16.88, 17.72, 16.72, 16.57, and 16.64%, respectively, and the encapsulation rate all reached about 100%. More surprisingly, the release experimental results showed that the microspheres prepared with PLGA 7520 did not show sudden release, showing good sustained release performance and high drug release rate. To sum up, this study optimized the preparation method of sustained-release microspheres without sudden release, which provides a new solution for the delivery of itraconazole in the clinic.
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Ácido Láctico , Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Ácido Poliglicólico/química , Ácido Láctico/química , Preparaciones de Acción Retardada , Itraconazol , Microesferas , Emulsiones , Solventes , Tamaño de la PartículaRESUMEN
A Japanese man in his early 70s was referred to our hospital because of massive proteinuria. Analysis of his kidney biopsy demonstrated glomerular subepithelial immune deposits containing immunoglobulin (Ig)G, which was dominant for the IgG1 subclass. Immunoperoxidase staining for neural epidermal growth factor-like 1 protein (NELL1) was positive on the glomerular capillary walls, whereas neither serum anti-phospholipase A2 receptor (PLA2R) antibodies nor immunofluorescence staining for PLA2R was positive. Detailed investigation revealed no associated conditions, including underlying malignancies, and thus he was diagnosed as having NELL1-associated idiopathic membranous nephropathy (MN). The patient was treated with steroids, which substantially improved his nephrotic syndrome. Interestingly, serum anti-NELL1 as well as anti-PLA2R antibodies became positive during his clinical course. Serology-based approaches are currently proposed for the treatment of patients suspected of having MN; however, an accurate diagnosis of the present patient would have been difficult if such an approach was performed only at a later phase of the disease. Several target antigens for the glomerular immune deposits observed in patients with MN have recently been identified, and dual positivity of antibodies to these antigens reportedly occurs in some patients. Further accumulation and analyses of such patients are needed to establish more appropriate diagnostic approaches for MN.
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Anorexia nervosa causes various complications accompanying weight loss and malnutrition. Although bilateral spontaneous pneumothorax (SBSP) is uncommon, caution is needed in anorexia nervosa because this complication can be fatal. We encountered a 17-year-old girl with SBSP from emphysematous pulmonary changes due to anorexia nervosa. She was hospitalized with SBSP during treatment for anorexia nervosa. Chest tube drainage was started on admission, but no improvement was achieved. Surgery was therefore performed. Lung lesions on surgical specimens demonstrated malnutrition-induced emphysematous changes, a risk factor for SBSP. Attention should be paid to the occurrence of SBSP during the clinical course of anorexia nervosa.
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STUDY OBJECTIVES: Poor adherence to continuous positive airway pressure (CPAP) has been a critical issue in treating obstructive sleep apnea. Because long-term CPAP adherence may be established shortly after treatment begins, early intervention is essential. This study aimed to identify the potential factors affecting CPAP therapy adherence during diagnostic polysomnography and auto CPAP titration polysomnography. METHODS: This retrospective observational study included 463 patients with obstructive sleep apnea who underwent consecutive diagnostic polysomnography and titration polysomnography. We recorded their demographic, anthropometric, and lifestyle factors and obtained self-reported comments regarding their sleep status following both polysomnography evaluations. CPAP adherence was evaluated following 3 months of treatment. RESULTS: A total of 312 patients (67.4%) fulfilled the criteria for good adherence. Each patient's CPAP adherence was categorized as "poor" (< 4 hours/night or <70% of nights), "good" (≥ 4 hours/night and ≥ 70% of nights), or "excellent" (≥ 6 hours/night and ≥ 80% of nights). There were no significant differences in arterial oxyhemoglobin saturation measured by pulse oximetry and apnea-hypopnea index during diagnostic polysomnography among 3 groups. The polysomnographic evaluations indicated that patients with better adherence displayed more significant improvements in sleep parameters, including apnea-hypopnea index, sleep efficacy, sleep latency, and sleep architecture, which were correlated with an improvement in self-reported sleep quality. CONCLUSIONS: Polysomnographic evaluations enabled CPAP adherence prediction and a comparison of self-reported sleep quality with and without CPAP; CPAP adherence led to improvements in polysomnographic parameters. Our findings suggest that titration polysomnography and self-reported sleep improvement with CPAP could be used for adherence prediction in clinical practice. CITATION: Shirahata T, Uchida Y, Uchida T, et al. Improvement of sleep parameters by titration polysomnography could predict adherence to positive airway pressure therapy in obstructive sleep apnea. J Clin Sleep Med. 2023;19(8):1465-1473.
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Apnea Obstructiva del Sueño , Sueño , Humanos , Polisomnografía , Apnea Obstructiva del Sueño/diagnóstico , Presión de las Vías Aéreas Positiva Contínua , Oximetría , Cooperación del PacienteRESUMEN
The purpose of the present study was to evaluate bitterness suppression effect of adenylic acid (AMP) as a nucleotide-derived nutrient enhancer on a bitter commercial drug. In the present study, we evaluated peripheral bitterness inhibition effect of AMP on the trimethoprim (TMP) and sulfamethoxazole (SMZ) combination formulation based on taste sensor. The taste sensor values of TMP solutions with different concentrations show large sensor output in correlation with the concentration of TMP, whereas no sensor output in shown for the SMZ solutions. Therefore, the bitterness of this combination formulation is mainly due to TMP. We evaluated the TMP bitterness inhibitory effects of AMP, sodium salt of AMP (AMP Na; sodium adenylate), sodium salt of GMP (GMP Na; sodium guanylate), and sodium salt of inosine monophosphate (IMP Na; sodium inosinate), and found that only AMP displayed very effective bitterness inhibition. MarvinSketch analysis revealed that potential electrostatic interaction between cationized TMP and anionized forms (II and III) of AMP may cause bitterness suppression. 1H-NMR study suggested an interaction of TMP and AMP molecules based on chemical shift perturbations and an interaction between the phosphate group of AMP and amino group of TMP. Lastly, conventional elution analysis simulating oral cavity capacity for up to one minute were performed using commercial TMP/SMZ combination granules. The sensor output gradually increased up to 60 s. The addition of AMP solution to the eluted sample at 60 s significantly decreased the bitterness sensor output of the eluted sample.
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Gusto , Combinación Trimetoprim y Sulfametoxazol , Adenosina Monofosfato , Antibacterianos , Combinación de MedicamentosRESUMEN
As medical device development becomes increasingly global, the opportunities and potential advantages offered by international clinical trial and regulatory approval strategies are also growing. In particular, medical device clinical trials involving sites in both the United States and Japan and intended to support marketing in both countries may warrant particular consideration, given the similarities in their regulatory systems, patients and clinical practice patterns, and market sizes. Since 2003, the US-Japan Harmonization By Doing (HBD) initiative has been focused on identifying and addressing clinical and regulatory barriers to medical devices access in both countries via collaboration between governmental, academic, and industry stakeholders. Through the efforts of HBD participants, US-Japanese clinical trials have been conducted and the resulting data have supported regulatory approval for marketing in both countries. Based on these experiences, this paper outlines some of the key factors to consider when developing a global clinical trial involving US and Japanese participation. These considerations include the mechanisms for consultation with regulatory authorities on clinical trial strategies, the regulatory framework for clinical trial notification and approval, recruitment and conduct of clinical sites, and lessons learned from specific US-Japanese clinical trial experiences. The goal of this paper is to promote global access to promising medical technologies by assisting potential clinical trial sponsors in understanding when an international strategy may be appropriate and successful.
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Aprobación de Recursos , Humanos , Estados Unidos , JapónRESUMEN
This study aimed to evaluate the bitterness of famotidine (FAM) combined with each of three non-steroidal anti-inflammatory drugs (NSAIDs): ibuprofen (IBU), flurbiprofen (FLU), and naproxen (NAP), which have potential as fixed-dose combination (FDC) drugs. We evaluated the bitterness of FAM and each NSAID by taste sensor AN0 and C00, respectively. FAM showed high sensor output representing sensitivity to bitterness, whereas three NSAIDs did not show large sensor output, suggesting that the bitterness intensities of three NSAIDs were lower than that of FAM. The bitterness of FAM on sensor AN0 was suppressed in a concentration-dependent manner when mixed with IBU, FLU, or NAP. Among three NSAIDs, IBU most effectively inhibited bitterness on sensor output, and the gustatory sensation test confirmed that adding IBU to FAM reduced the bitterness of FAM in a concentration-dependent manner. MarvinSketch confirmed that the drugs were mostly present in an ionic solution when FAM was mixed with NSAIDs. The 1H-NMR spectroscopy analysis also revealed the presence of electrostatic interactions between FAM and NSAIDs, suggesting that the electrostatic interaction between FAM and NSAIDs might inhibit the adsorption of FAM on the bitter taste sensor membrane, thereby masking the bitter taste.
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Flurbiprofeno , Gusto , Famotidina/farmacología , Antiinflamatorios no Esteroideos/farmacología , Ibuprofeno/farmacología , NaproxenoRESUMEN
A 67-year-old woman who had undergone bone marrow transplantation 2 years previously for acute myeloid leukemia (AML) developed complications of chronic graft-versus-host disease (cGVHD). She thereafter also developed nephrotic syndrome, and membranous nephropathy (MN) was diagnosed by a renal biopsy. Although the causative antigens of the MN were not detected, immunofluorescence staining showed codominant deposition of immunoglobulins G2 and G3, a finding indicating secondary MN, thereby suggesting an association between MN and cGVHD. Rituximab treatment was initiated, and her nephrotic syndrome gradually improved without relapse of AML. Our present case suggests that rituximab is a safe and effective therapeutic option for cGVHD-associated MN.