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1.
Org Biomol Chem ; 22(27): 5546-5551, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38814007

RESUMEN

Photo-induced glycosylations of trichloroacetimidate donors and alcohols using an edible polyphenol, curcumin, were examined under visible photo-irradiation (470 nm). It was found, for the first time, that these glycosylations proceed smoothly under mild reaction conditions to give the corresponding glycosides in high yields. In addition, the present glycosylation method was applicable to a wide range of trichloroacetimidate donors and alcohol acceptors and showed high chemoselectivity over glycosyl phosphite, phosphate, (N-phenyl)trifluoroacetimidate, fluoride, glycal and thioglycoside.

2.
Chemistry ; : e202401319, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38802321

RESUMEN

Mannosylerythritol lipids (MELs) are a class of amphipathic molecules bearing a hydrophilic 4-O-ß-D-mannopyranosyl-D-erythritol skeleton. Here, we designed and synthesized four kinds of MEL analogues R-MEL-A ([2R,3S]-erythritol type), S-mannosylthreitol lipid (MTL)-A ([2S,3S]-threitol type), R-MTL-A ([2R,3R]-threitol type), and α-S-MEL-A ([2S,3R]-erythritol type) using our previously reported boron-mediated aglycon delivery (BMAD) method and a neighboring group assisted glycosylation method. The selective cytotoxicity of the target compounds against cancer cells was evaluated, with R-MTL-A showing the highest selective cytotoxicity against human skin squamous carcinoma HSC-5 cells. Our findings suggest that R-MTL-A induces necrosis-like cell death against HSC-5 cells by decreasing cell membrane fluidity. R-MTL-A also exhibits an efficient recovery effect on damaged skin cells, indicating that R-MTL-A has potential as a lead compound for new cosmeceuticals with both cancer cell-selective toxicity and recovery effects on damaged skin cells.

3.
J Bone Joint Surg Am ; 106(11): 966-975, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38626018

RESUMEN

BACKGROUND: The incidence of developmental dysplasia of the hip (DDH) in Japanese newborns has reduced drastically following a primary prevention campaign initiated around 1972 to 1973; this perinatal education campaign promoted maintaining the hips of newborns in the naturally flexed-leg position. The purpose of the present study was to describe the life course epidemiology of hip osteoarthritis (OA) in adolescent and adult patients and to assess its association with exposure to the primary prevention campaign for DDH. METHODS: We included new patients with hip OA diagnosed from January 1, 2022, to December 31, 2022, at 12 core hospitals (8 special-function hospitals and 4 regional medical care support hospitals). The trend in the percentage of hips with a history of DDH treatment in childhood was estimated with use of a centered moving average using the birth year of the patient. We compared the prevalence of severe subluxation (Crowe type II, III, or IV) between patients with secondary hip OA due to hip dysplasia who were born in or before 1972 and those who were born in or after 1973. RESULTS: Overall, 1,095 patients (1,381 hips) were included. The mean age at the time of the survey was 63.5 years (range, 15 to 95 years). A total of 795 patients (1,019 hips; 73.8% of hips) were diagnosed with secondary OA due to hip dysplasia. Approximately 13% to 15% of hips among patients born from 1963 to 1972 had a history of DDH treatment in childhood; however, the percentage decreased among patients born in or after 1973. The prevalence of severe subluxation (Crowe type II, III, or IV) among patients born in or after 1973 was 2.4%, which was significantly less than that among patients born in or before 1972 (11.1%; odds ratio, 0.20; p < 0.001). CONCLUSIONS: As of 2022, secondary hip OA due to hip dysplasia is still responsible for most new cases of adolescent and adult hip OA seen in core hospitals in Japan. However, the perinatal education campaign initiated 50 years ago, which utilized a population approach and advocated for maintaining the hips of newborns in the naturally flexed-leg position, may have improved the environmental factors of DDH, as indicated by the apparently reduced need for treatment of DDH in childhood and the associated severe subluxation. This may result in a reduced need for challenging hip surgery later in life. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.


Asunto(s)
Osteoartritis de la Cadera , Humanos , Japón/epidemiología , Osteoartritis de la Cadera/epidemiología , Osteoartritis de la Cadera/etiología , Estudios Transversales , Femenino , Masculino , Anciano , Adolescente , Persona de Mediana Edad , Adulto , Anciano de 80 o más Años , Adulto Joven , Prevalencia , Displasia del Desarrollo de la Cadera/epidemiología , Luxación Congénita de la Cadera/epidemiología , Luxación Congénita de la Cadera/terapia , Incidencia
4.
Kyobu Geka ; 77(1): 22-26, 2024 Jan.
Artículo en Japonés | MEDLINE | ID: mdl-38459841

RESUMEN

OBJECTIVE: In an effort to avoid postoperative sick sinus syndrome( SSS), we omit the ablation line to the superior vena cava( SVC) in the Cox-mazeⅢ lesion set. We report the long-term outcomes, including the freedom from SSS. METHODS: We studied 102 patients who underwent bi-atrial maze procedure for persistent atrial fibrillation (Af) from 2009 through 2023. Bipolar radio frequency ablation or cryoablation was used except for right-side atriotomy and right atriotomy. Cryoablation was used for atrioventricular annulus. The patient age was 68±9.4. Duration of Af was 3.4±6.5 years (unknown 9 cases). The amplitude of f-wave in V1 was 0.182±0.095 mV and it was<0.1 mV in 19 (18.6%). Diameter of the left atrium was 50±8.9 mm, and left atrial volume index was 89±37 ml/m2. Ninety-one (89.2%) patients underwent concomitant mitral valve surgery. RESULTS: Survival rate was 99% at 1 year and 96% at 5 years. Freedom from Af was 92% at 1 year and 88% at 5 years. Freedom from permanent pacemaker implantation (PPI) was 87% at 1 year and 83% at 5 years. CONCLUSIONS: Defibrillation rate and the incidence of PPI was comparable to those in previous reports after standard Cox-mazeⅢ. SSS after maze for persistent Af seem due to patient.


Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Humanos , Vena Cava Superior/cirugía , Procedimiento de Laberinto , Resultado del Tratamiento , Fibrilación Atrial/cirugía , Atrios Cardíacos/cirugía , Ablación por Catéter/métodos
5.
Cureus ; 16(2): e54775, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38524092

RESUMEN

Varicella-zoster virus (VZV), known for causing chickenpox, establishes latent infections in neural tissues. Reactivation of VZV can lead to herpes zoster (HZ) and various neurological complications. In this report, we present four cases of VZV meningitis and myelitis following amenamevir treatment for HZ dermatitis with positive VZV DNA in cerebrospinal fluid (CSF) revealed by polymerase chain reaction (PCR). Three of them were considered immunocompromised hosts given the fact that two of these patients were taking immunosuppressive drugs for rheumatoid arthritis, and one patient had a history of sigmoid colon cancer (four months after resection). After HZ onset, amenamevir, which has poor CSF transfer, was prescribed for all the patients, and all of them developed central nervous complications by VZV (meningitis in three cases and myelitis in one case) confirmed by PCR. All the patients were treated with acyclovir, which has a higher CSF transfer, and fully recovered. We speculate that amenamevir might have failed to prevent VZV infection in the central nervous system (CNS) and think that consideration should be given to administering acyclovir in preference to amenamevir for ΗΖ patients at high risk of CNS VZV infection, such as immunocompromised hosts.

6.
BMC Nephrol ; 25(1): 51, 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38336610

RESUMEN

BACKGROUND: Recent studies have focused on immune checkpoint inhibitors. Renal complications associated with the use of immune checkpoint inhibitors are uncommon compared with other immune-related adverse events. Acute interstitial nephritis accounts for most of these renal complications, with nephrotic syndrome quite rare. We herein report a case of nephrotic syndrome associated with immune checkpoint inhibitors that was more severe than that in previous cases. By comparing this case with previous reports, the possible reasons for the particular severity of this case are discussed. CASE PRESENTATION: A 75-year-old man developed nephrotic syndrome with acute kidney injury after the first combination therapy of nivolumab and ipilimumab for malignant pleural mesothelioma. The results of a kidney biopsy indicated minimal change disease with mild atherosclerosis, acute interstitial nephritis, and fusion of nearly all podocyte foot processes. Nivolumab and ipilimumab therapy were stopped, and treatment with corticosteroids was initiated. We investigated previously reported cases of nephrotic syndrome using immune checkpoint inhibitors. Seventeen cases of immune checkpoint inhibitor-related nephrotic syndrome, including ours, have been reported. Two of the 17 patients with immune checkpoint inhibitor-related nephrotic syndrome required hemodialysis treatment for acute kidney injury. Unlike many previously reported cases, the present patient was administered two different immune checkpoint inhibitors, which may be one of the reasons for the development of severe nephrotic syndrome. CONCLUSIONS: In addition to previously reported risk factors, immune checkpoint inhibitor combination therapy can exacerbate nephrotic syndrome compared to immune checkpoint inhibitor monotherapy.


Asunto(s)
Lesión Renal Aguda , Antineoplásicos Inmunológicos , Nefritis Intersticial , Síndrome Nefrótico , Masculino , Humanos , Anciano , Nivolumab/efectos adversos , Ipilimumab/efectos adversos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Síndrome Nefrótico/inducido químicamente , Síndrome Nefrótico/tratamiento farmacológico , Antineoplásicos Inmunológicos/efectos adversos , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/terapia , Lesión Renal Aguda/complicaciones , Nefritis Intersticial/inducido químicamente , Nefritis Intersticial/complicaciones
7.
J Am Heart Assoc ; 13(3): e032284, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38240254

RESUMEN

BACKGROUND: Patients with acute ischemic stroke and active cancer have more severe neurological symptoms, elevated risks of stroke recurrence, and death compared with the general population. We examined whether von Willebrand factor (vWF) antigen levels at stroke onset were associated with the poor outcomes of patients with stroke and cancer. METHODS AND RESULTS: Using data from 90 patients with acute ischemic stroke and active cancer who were registered in the SCAN (Ischemic Stroke in Patients With Cancer and Neoplasia) study, a prospective multicenter, observational study in Japan, we divided patients into 2 groups according to their median vWF antigen levels (high, n=46; or low, n=44). The high-vWF group had a significantly higher initial National Institutes of Health Stroke Scale score (median, 7 [interquartile range, 3-11.25] versus 3 [interquartile range, 1-8.5]; P<0.05) and a significantly higher incidence of cryptogenic stroke (32 [70%] versus 16 [36%]; P<0.01) and venous thromboembolism (7 [15%] versus 0 [0%]; P<0.01), as well as multiple lesions (28 [62%] versus 12 [27%]; P<0.001), than the low-vWF group. We observed no significant difference in the rate of stroke recurrence within 1 year between the groups. However, increased vWF levels were an independent predictor of death within 1 year of stroke onset, after adjusting for potential confounders (odds ratio, 6.77 [95% CI, 1.49-30.78]; P<0.05). CONCLUSIONS: Elevated vWF antigen levels were associated with adverse outcomes in patients with cancer-associated stroke and may represent a useful biomarker to guide future therapeutic interventions.


Asunto(s)
Accidente Cerebrovascular Isquémico , Neoplasias , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular Isquémico/complicaciones , Neoplasias/complicaciones , Neoplasias/epidemiología , Estudios Prospectivos , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Factor de von Willebrand , Estudios Multicéntricos como Asunto , Estudios Observacionales como Asunto
8.
CEN Case Rep ; 13(2): 135-140, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37606883

RESUMEN

Carcinoid syndrome is caused by the release of serotonin and other substances, which commonly occurs due to liver metastasis of neuroendocrine tumors. It rarely occurs due to liver metastasis of neuroendocrine carcinoma. We report the case of a patient with liver metastasis of neuroendocrine carcinoma who suffered from acute abdominal pain and diarrhea triggered by hemodialysis. Various differential diagnoses were considered, but we concluded these symptoms to be probably caused by exacerbation of carcinoid syndrome, as the serum 5HIAA level was markedly elevated, and a drug with anti-serotonin activity was effective. Prochlorperazine maleate, which has anti-serotonin activity, was effective for these symptoms, and the patient was able to continue maintenance hemodialysis, which contributed to his quality of life and prognosis. We speculated the mechanism of carcinoid exacerbation was that substances such as serotonin had entered the systemic circulation via the increased extrahepatic shunt of the portal venous blood flow, entering the inferior vena cava and that this condition had been triggered by hemodialysis via the same mechanism as portal systemic encephalopathy.


Asunto(s)
Tumor Carcinoide , Carcinoma Neuroendocrino , Neoplasias Hepáticas , Humanos , Proclorperazina , Serotonina , Calidad de Vida , Tumor Carcinoide/complicaciones , Tumor Carcinoide/diagnóstico , Diálisis Renal/efectos adversos , Neoplasias Hepáticas/diagnóstico
9.
Clin Biomech (Bristol, Avon) ; 111: 106136, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38065038

RESUMEN

BACKGROUND: The treatment strategy for developmental dysplasia of the hip is determined based on the lateral center-edge angle. Nonetheless, an evaluation of joint instability may be important in determining the treatment strategy. This study classified the displacement patterns of the femoral head center during hip abduction. METHODS: Ten patients with borderline developmental dysplasia of the hip, 10 patients with developmental dysplasia of the hip, and 10 patients with normal hips were analyzed. Image matching was performed using X-ray images of hip abduction with a three-dimensional hip model. The displacement of the femoral head center and its trajectory length were measured. A cluster analysis was conducted to classify the displacement pattern of the femoral head center, and trajectory lengths were compared. FINDINGS: Displacement was classified into three patterns: medialization, hinge abduction, and centering. Patients with borderline developmental hip dysplasia exhibited all three patterns. Almost all patients with developmental dysplasia of the hip showed medialization and hinge abduction, whereas all normal patients had the centering type. The mean trajectory length indices for the medialization and hinge abduction types were significantly longer than those for the centering type (P = 0.01 and P = 0.016, respectively). INTERPRETATION: Borderline developmental dysplasia of the hip is a heterogeneous condition characterized by varying hip instability levels. Our findings suggest that uniform evaluation based on the lateral center-edge angle is inappropriate and that joint instability must be evaluated in each patient with borderline developmental dysplasia of the hip.


Asunto(s)
Displasia del Desarrollo de la Cadera , Luxación Congénita de la Cadera , Luxación de la Cadera , Inestabilidad de la Articulación , Humanos , Acetábulo , Inestabilidad de la Articulación/diagnóstico por imagen , Osteotomía , Articulación de la Cadera/diagnóstico por imagen , Estudios Retrospectivos , Luxación Congénita de la Cadera/diagnóstico por imagen
10.
Gen Thorac Cardiovasc Surg ; 72(3): 202-205, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37882902

RESUMEN

Stabilizing the aorto-ventricular junction is integral in aortic valve repair. We report our technique of internal circular suture annuloplasty. We used a continuous horizontal mattress suture of a single thick expanded polytetrafluoroethylene suture (CV-3). We put 4 stitches per sinus, so the suture was below the cusp attachment line at the nadirs and passed through the interleaflet triangle at the upper aorto-ventricular junction level. The suture was reinforced with pericardial pledgets on both sides of each commissure. We used this technique in 12 patients. The diameter of aorto-ventricular junction was reduced from 25 ± 2 mm to 22 ± 1 mm (n = 11) and was 22 ± 1 mm at the latest follow-up (4-74 months, median 41, n = 10). In 2 patients with large aorto-ventricular junction (27 mm or more), expected annular reduction was not achieved. Our modified technique is simple and seems durable. It may be useful for mild annular dilatation.


Asunto(s)
Insuficiencia de la Válvula Aórtica , Anuloplastia de la Válvula Cardíaca , Humanos , Válvula Aórtica/cirugía , Insuficiencia de la Válvula Aórtica/diagnóstico por imagen , Insuficiencia de la Válvula Aórtica/cirugía , Anuloplastia de la Válvula Cardíaca/métodos , Válvula Tricúspide/cirugía , Suturas , Técnicas de Sutura , Resultado del Tratamiento
11.
Front Med (Lausanne) ; 10: 1227283, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37928459

RESUMEN

Most male X-linked Alport syndrome patients with COL4A5 nonsense mutations experience end-stage kidney failure by 30 years old. Although there is no definition of high-flow arteriovenous fistula, access blood flows greater than 2000 mL/min might predict the occurrence of high-output heart failure. A 50-year-old Japanese man had suffered from proteinuria at 4 years old and sensorineural hearing loss and a lenticular lens at 20 years old. He had started to receive hemodialysis treatment due to end-stage kidney disease at 22 years old. A genetic test confirmed a novel hemizygous nonsense variant COL4A5 c.2980G > T (p.Gly994Ter), and he was diagnosed with X-linked Alport syndrome. COL4A5 c.2980G > T was considered "pathogenic" according to the American College of Medical Genetics and Genomics guidelines and in vitro experiments. Shortness of breath on exertion was exaggerated, his brachial artery blood flow was over 4,236-4,353 mL/min, his cardiac output was 5,874 mL/min, and he needed radial artery banding at 51 years old. After radial artery banding surgery, the brachial artery blood flow decreased to 987-1,236 mL/min, and echocardiography showed a cardiac output at 5100 mL/min with improved E' and E/E'. His shortness of breath on exertion improved gradually. Although rare, high-output heart failure due to high-flow arteriovenous fistula should be kept in mind as a complication in X-linked Alport syndrome patients, and our patient was successfully treated with radial artery banding surgery.

12.
J Orthop Sci ; 2023 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-37451975

RESUMEN

BACKGROUND: Based on the Japanese Pediatric Orthopaedic Association's guidelines, secondary screening and imaging including ultrasonography and radiography, are recommended in infants with limited hip abduction (<70°) or in those with multiple risk factors including the following: asymmetrical skin creases, a family history of developmental dysplasia of the hip, female sex, and pelvic position at delivery. However, there is still little information regarding the usefulness of this guideline. The objective of this study was to investigate the association between the risk factors and developmental dysplasia of the hip diagnosed using ultrasound and radiography. METHODS: A total of 356 infants (67 boys and 289 girls) underwent secondary ultrasonographic and radiological screening for developmental dysplasia of the hip in our hospital. Risk factors were documented from their medical records. The recommended item score, which we defined as an integrated value of the recommended item, was calculated for each patient. The limitation of hip abduction alone was a criterion for secondary screening; therefore, we defined the scores as follows: the limitation of hip abduction scored 2 points and other recommended scores were assigned 1 point. If the recommended item score was 2 points or more, we classified the infants as high-risk. RESULTS: A total of 280 of 356 infants were included in the high-risk group, which showed a higher ratio of cases with abnormal imaging findings than the low-risk group. According to the multivariate logistic regression analyses among the recommended items, being female, skin asymmetry, and limb limitation were identified as independent risk factors for imaging abnormality and the need for Pavlik harness treatment. CONCLUSIONS: The recommended items for secondary screening based on the Japanese Pediatric Orthopaedic Association's guidelines could be useful for screening infants in need of treatment.

13.
J Am Heart Assoc ; 12(15): e029618, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37489755

RESUMEN

Background Limited data exist on the prognostic factors for patients with ischemic stroke and active cancer. Methods and Results We conducted a prospective, multicenter, observational study in Japan, including patients with acute ischemic stroke and active cancer, to investigate the prognostic factors. We followed up the patients for 1 year after stroke onset. The patients were divided into 2 groups according to cryptogenic stroke and known causes (small-vessel occlusion, large-artery atherosclerosis, cardioembolism, and other determined cause), and survival was compared. The hazard ratios (HRs) and 95% CIs for mortality were calculated using Cox regression models. We identified 135 eligible patients (39% women; median age, 75 years). Of these patients, 51% had distant metastasis. A total of 65 (48%) and 70 (52%) patients had cryptogenic stroke and known causes, respectively. Patients with cryptogenic stroke had significantly shorter survival than those with known causes (HR [95% CI], 3.11 [1.82-5.32]). The multivariable Cox regression analysis revealed that distant metastasis, plasma D-dimer levels, venous thromboembolism (either deep venous thrombosis or pulmonary embolism) complications at stroke onset were independent predictors of mortality after adjusting for potential confounders. Cryptogenic stroke was associated with prognosis in univariable analysis but was not significant in multivariable analysis. The plasma D-dimer levels stratified the prognosis of patients with ischemic stroke and active cancer. Conclusions The prognosis of patients with acute ischemic stroke and active cancer varied considerably depending on stroke mechanism, distant metastasis, and coagulation abnormalities. The present study confirmed that coagulation abnormalities were crucial in determining the prognosis of such patients.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Neoplasias , Accidente Cerebrovascular , Humanos , Femenino , Anciano , Masculino , Accidente Cerebrovascular Isquémico/complicaciones , Estudios Prospectivos , Factores de Riesgo , Accidente Cerebrovascular/etiología , Neoplasias/complicaciones , Isquemia Encefálica/etiología
14.
Int J Hematol ; 118(5): 656-660, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37490235

RESUMEN

BACKGROUND: CD36-deficient individuals may produce anti-CD36 antibodies through antigenic exposure to CD36, in situations including blood transfusions. Therefore, allogeneic hematopoietic stem cell transplantation (HSCT) from CD36-positive donors to CD36-negative patients remains a challenge. CASE REPORT: A 64-year-old man with acute myeloid leukemia became refractory to platelet transfusions during chemotherapy. Anti-CD36 antibodies without anti-HLA antibodies were detected in serum, and the absence of CD36 expression on platelets and monocytes confirmed type I CD36 deficiency. The patient achieved complete remission, and received maintenance therapy with CD36-negative platelet transfusions. However, he relapsed soon afterward, and thus underwent peripheral blood stem cell transplantation (PBSCT) from a CD36-positive unrelated donor. The anti-CD36 antibody titer had decreased before the transplant, and the PBSCT-course was uneventful. The patient has been well without any complications associated with CD36 status mismatch. DISCUSSION: The few reports of allogeneic HSCT in patients with CD36 deficiency have suggested that anti-CD36 antibodies could be involved in several post-transplant complications, such as delayed platelet recovery, transfusion refractoriness, and transfusion-related acute lung injury. Our present case confirmed that stem cell transplantation from CD36-positive donors to negative patients is feasible, when it includes careful prior assessment of anti-CD36 antibody titers and interventions to attenuate them.


Asunto(s)
Trastornos de las Plaquetas Sanguíneas , Trasplante de Células Madre Hematopoyéticas , Masculino , Humanos , Persona de Mediana Edad , Plaquetas , Donante no Emparentado
15.
BMC Nephrol ; 24(1): 199, 2023 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-37393252

RESUMEN

BACKGROUND: Proliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits (PGNMID) is a disease entity with nonorganized granular glomerular deposition with monoclonal proteins of both heavy and light chains. Dysproteinemia was observed in only 30% of the patients with PGNMID. We herein report a case of PGNMID with discrepancy between serum and glomerular deposits. CASE PRESENTATION: The patient was a 50-year-old man who had been followed at a local clinic due to hypertension, type 2 diabetes, hyperlipidemia, hyperuricemia, fatty liver, and obesity. Proteinuria had been noted five years previously, and he had been referred to a hematology department due to hyperproteinemia, high gamma globulin, and κ Bence-Jones protein (BJP) positivity one year previously. Bone marrow aspiration showed 5% plasma cells, and he was referred to the nephrology department to evaluate persistent proteinuria. He was hypertensive, and his estimated glomerular filtration rate was 54.2 ml/min/1.73 m2. His urinary protein level was 0.84 g/g⋅Cr. Urine and serum immunofixation showed BJP-κ type and IgG-κ type, respectively. Kidney biopsy showed an increase in mesangial cells and matrix without nodular lesions under a light microscope. Immunofluorescence microscopy showed granular deposits of IgG and C3 on the capillary wall and weak positivity for C1q. IgG3 was predominant among the IgG subclasses, and intraglomerular κ and λ staining was negative for κ and positive for λ. Direct fast scarlet staining was negative. Electron microscopy showed lumpy deposits without a fibrillar structure in the subepithelial area. Based on the above findings, a diagnosis of membranous nephropathy-type PGNMID was made. Since proteinuria increased gradually after three years of treatment with valsartan (40 mg, daily), oral prednisolone (30 mg, daily) was initiated, which led to decreased proteinuria. The dose of oral prednisolone was gradually tapered to 10 mg per day. At that time, proteinuria was 0.88 g/g⋅Cr. We found 204 cases in 81 articles in the PubMed database, among which 8 showed discrepancy in the heavy and/or light chains between serum and kidney. CONCLUSIONS: We experienced a case of membranous nephropathy-type PGNMID with discrepancy in light chains between serum and kidney that was successfully treated with oral prednisolone.


Asunto(s)
Diabetes Mellitus Tipo 2 , Glomerulonefritis Membranosa , Glomerulonefritis , Hipertensión , Enfermedades Renales , Masculino , Humanos , Persona de Mediana Edad , Inmunoglobulina G , Glomerulonefritis/diagnóstico , Glomerulonefritis/tratamiento farmacológico , Proteinuria , Anticuerpos Monoclonales
16.
Arthritis Rheumatol ; 75(8): 1358-1369, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36924130

RESUMEN

OBJECTIVE: The severity of osteoarthritis (OA) and cartilage degeneration is highly correlated with the development of synovitis, which is mediated by the activity of inflammatory macrophages. A better understanding of intercellular communication between inflammatory macrophages and chondrocytes should aid in the discovery of novel therapeutic targets. We undertook this study to explore the pathologic role of inflammatory macrophage extracellular vesicles (EVs) in cartilage degeneration. METHODS: Macrophages were stimulated by treatment with bacterial lipopolysaccharides to mimic the state of inflammatory macrophages, and the resulting EVs were harvested for chondrocyte stimulation in vitro and for intraarticular injection in a mouse model. The stimulated chondrocytes were further subjected to RNA-sequencing analysis and other functional assays. The action of caspase 11 was disrupted in vitro using a specific small interfering RNA or wedelolactone, and in experimental murine OA models by intraarticular injection of wedelolactone. RESULTS: Stimulated chondrocytes exhibited a significant elevation in the expression of chondrocyte catabolic factors. Consistent with these results, RNA-sequencing analyses of stimulated chondrocytes indicated that up-regulated genes were mainly categorized into apoptotic process and tumor necrosis factor signaling pathways, which suggests the induction of apoptotic process. Moreover, these chondrocytes exhibited a significant elevation in the expression of pyroptosis-related molecules that were correlated with the expression of chondrocyte catabolic factors. The disruption of caspase 11 significantly alleviated pyroptotic and catabolic processes in stimulated chondrocytes and pathologic changes in collagenase-induced and joint instability-induced OA models. CONCLUSION: Our results provide new insight into the pathologic mechanisms of OA and suggest that noncanonical pyroptosis in chondrocytes represents an attractive therapeutic target for treatment.


Asunto(s)
Cartílago Articular , Vesículas Extracelulares , Osteoartritis , Ratones , Animales , Condrocitos/metabolismo , Piroptosis , Cartílago/metabolismo , Osteoartritis/metabolismo , Macrófagos/metabolismo , ARN Interferente Pequeño/metabolismo , Caspasas , Vesículas Extracelulares/patología , Cartílago Articular/metabolismo
17.
BMC Musculoskelet Disord ; 24(1): 134, 2023 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-36803129

RESUMEN

BACKGROUND: This study compared the re-revision rate and radiographic outcomes of revision total hip arthroplasty (THA) using a Kerboull-type acetabular reinforcement device (KT plate) with bulk structural allograft and metal mesh with impaction bone grafting (IBG). METHODS: Ninety-one hips of 81 patients underwent revision THA for American Academy of Orthopedic Surgeons (AAOS) classification type III defects from 2008 to 2018. Of these, seven hips of five patients and 15 hips of 13 patients were excluded due to insufficient follow-up information (< 24 months) and large bone defects with a vertical defect height ≥ 60 mm, respectively. The current study compared the survival and radiographic parameters of 45 hips of 41 patients using a KT plate (KT group) and 24 hips of 24 patients using a metal mesh with IBG (mesh group). RESULTS: Eleven hips (24.4%) in the KT group and 1 hip (4.2%) in the mesh group exhibited radiological failure. Moreover, 8 hips in the KT group (17.0%) required a re-revision THA, while none of the patients in the mesh group required a re-revision. The survival rate with radiographic failure as the endpoint in the mesh group was significantly higher than that in the KT group (100% vs 86.7% at 1-year and 95.8% vs 80.0% at 5-years, respectively; p = 0.032). On multivariable analysis evaluating factors associated with radiographic failure, there were no significant associations with any radiographic measurement. Of the 11 hips with radiographic failure, 1 (11.1%), 3 (12.5%), and 7 (58.3%) hips were of Kawanabe classification stages 2, 3, and 4, respectively. CONCLUSIONS: The findings of this study suggest that revision THA using KT plates with bulk structure allografts could provide poorer clinical outcomes than revision THA using a metal mesh with IBG. Although revision THA using KT plates with bulk structural allografts could set the true hip center, there is no association between a high hip center and clinical outcomes. The relationship between the position of the KT plate and the host bone might be considered more carefully.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Prótesis de Cadera , Humanos , Artroplastia de Reemplazo de Cadera/efectos adversos , Trasplante Óseo , Mallas Quirúrgicas , Resultado del Tratamiento , Falla de Prótesis , Acetábulo/diagnóstico por imagen , Acetábulo/cirugía , Reoperación , Metales , Estudios de Seguimiento , Estudios Retrospectivos
18.
Intern Med ; 62(18): 2725-2730, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-36754409

RESUMEN

Exercise-induced acute kidney injury (EIAKI) is frequently complicated with renal hypouricemia (RHUC). In patients with RHUC, limiting anaerobic exercise can prevent EIAKI. However, it is challenging to reduce exercise intensity in athletes. We herein report a 16-year-old Japanese football player with familial RHUC with compound heterozygous mutations in urate transporter 1 (URAT1) who presented with recurrent EIAKI. As prophylaxis (hydration during exercise) could not prevent EIAKI, febuxostat was initiated. EIAKI was not observed for 16 months despite exercising intensively. Hence, non-purine-selective xanthine oxidoreductase inhibitors may decrease the incidence of EIAKI in athletes with RHUC.


Asunto(s)
Lesión Renal Aguda , Transportadores de Anión Orgánico , Humanos , Adolescente , Xantina Deshidrogenasa , Transportadores de Anión Orgánico/genética , Proteínas de Transporte de Catión Orgánico/genética , Lesión Renal Aguda/etiología , Lesión Renal Aguda/prevención & control , Inhibidores Enzimáticos
19.
J Biochem ; 174(1): 47-58, 2023 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-36805939

RESUMEN

The lipopolysaccharide (LPS)-triggered horseshoe crab coagulation cascade is composed of three protease zymogens, prochelicerase C (proC), prochelicerase B (proB) and the proclotting enzyme (proCE). In this study, we found that Ca 2+ ions increase the production of the clotting enzyme as a result of a cascade reaction reconstituted by recombinant proteins of wild-type (WT) proC, WT proB and WT proCE. We divided the cascade into three stages: autocatalytic activation of WT proC on the surface of LPS into WT α-chelicerase C (Stage 1); activation of WT proB on the surface of LPS into WT chelicerase B by WT α-chelicerase C (Stage 2) and activation of WT proce into WT CE by chelicerase B (Stage 3). Ca2+ ions enhanced the proteolytic activation in Stage 2, but not those in Stages 1 and 3. Moreover, we performed isothermal titration calorimetry to clarify the interaction of LPS or the recombinant zymogens with Ca2+ ions. LPS interacted with Ca2+ ions at an association constant of Ka = 4.7 × 104 M-1, but not with any of the recombinant zymogens. We concluded that LPS bound with Ca2+ ions facilitates the chain reaction of the cascade as a more efficient scaffold than LPS itself.


Asunto(s)
Cangrejos Herradura , Lipopolisacáridos , Animales , Lipopolisacáridos/metabolismo , Calcio/metabolismo , Coagulación Sanguínea , Precursores Enzimáticos/metabolismo
20.
Eur J Cardiothorac Surg ; 63(5)2023 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-36688718

RESUMEN

OBJECTIVES: Low patency is a major concern when using separate tube grafts for intercostal artery reconstruction. Our goal was to elucidate the optimal size and length of grafts from their patency and the computational fluid dynamics (CFD). METHODS: The patency, size and length of separate tube grafts were evaluated in 41 patients. Simulation of CFD was performed in a model derived from a patient with a patent 12-mm graft that was 15 mm long, with 2 simulation models with a smaller (8-mm) or longer (30-mm) graft. RESULTS: A total of 49 grafts were used for intercostal artery reconstruction. There was 1 in-hospital death and 2 spinal cord injuries. The patency rate, which could be evaluated in 46 grafts, was 63% (29/46). It was 71% (24/34) in thoracoabdominal aortic replacement and 42% (5/12) in descending aortic replacement. Among 14 patients in whom all grafts were occluded, no patients developed spinal cord injury. All grafts longer than 25 mm were occluded (n = 5). Eight- and 10-mm grafts showed better patency than 12-mm grafts in thoracoabdominal aortic replacement (P = 0.008) when grafts were shorter than 25 mm. Simulation of CFD revealed vortical flow within the 12-mm graft, which did not reach the intercostal orifice, whereas helical flow was maintained throughout the cardiac cycle within the 8-mm graft. CONCLUSIONS: Eight- and 10-mm grafts seemed better than 12-mm grafts, and grafts should be kept shorter than 25 mm. Simulation of CFD may shed light on the issue of the optimal intercostal artery reconstruction technique.


Asunto(s)
Aorta , Traumatismos de la Médula Espinal , Humanos , Mortalidad Hospitalaria , Aorta/cirugía , Procedimientos Quirúrgicos Vasculares/métodos
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