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Numerous antibody biomarkers have been reported for cancer and atherosclerosis-related diseases. The major complications of atherosclerosis and diabetes mellitus (DM) are acute ischemic stroke (AIS), cardiovascular disease (CVD) and chronic kidney disease (CKD). Cancer development is accompanied by arterial disorders, such as angiogenesis and atherosclerosis, and DM is a risk factor for the development of certain types of cancer. Atherosclerosis-related diseases and cancers are therefore interrelated and could be detected using a common biomarker. In the present study, the initial screening using the protein array method identified KIAA0513 as an antigen recognized by serum IgG antibodies in patients with atherosclerosis. The amplified luminescent proximity homogeneous assay-linked immunosorbent assay revealed significantly higher serum antibody levels against recombinant KIAA0513 protein in patients with AIS, transient ischemic attack (TIA), DM, CVD, obstructive sleep apnea syndrome (OSAS), CKD and solid cancers, such as esophageal, gastric, colon, lung and breast cancers, compared with healthy donors. A receiver operating characteristic (ROC) analysis revealed that the highest areas under the ROC curves of anti-KIAA0513 antibodies were obtained for esophageal cancer, nephrosclerosis-type CKD and DM. Spearman's correlation analysis revealed that serum anti-KIAA0513 antibody levels were associated with maximum intima-media thickness and plaque score, which are indices of atherosclerosis and stenosis. Serum anti-KIAA0513 antibody markers appear to be useful for diagnosing AIS, TIA, DM, CVD, OSAS, CKD and solid cancers, and may reflect common arterial alterations leading to atherosclerotic and cancerous diseases.
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Inflammation is closely associated with cerebrovascular diseases, cardiovascular diseases, diabetes, and cancers, and it is accompanied by the development of autoantibodies in the early stage of inflammation-related diseases. Hence, it is meaningful to discover novel antibody biomarkers targeting inflammation-related diseases. In this study, Jumonji C-domain-containing 6 (JMJD6) was identified by the serological identification of antigens through recombinant cDNA expression cloning. In particular, JMJD6 is an antigen recognized in serum IgG from patients with unstable angina pectoris (a cardiovascular disease). Then, the serum antibody levels were examined using an amplified luminescent proximity homogeneous assay-linked immunosorbent assay and a purified recombinant JMJD6 protein as an antigen. We observed elevated levels of serum anti-JMJD6 antibodies (s-JMJD6-Abs) in patients with inflammation-related diseases such as ischemic stroke, acute myocardial infarction (AMI), diabetes mellitus (DM), and cancers (including esophageal cancer, EC; gastric cancer; lung cancer; and mammary cancer), compared with the levels in healthy donors. The s-JMJD6-Ab levels were closely associated with some inflammation indicators, such as C-reactive protein and intima-media thickness (an atherosclerosis index). A better postoperative survival status of patients with EC was observed in the JMJD6-Ab-positive group than in the negative group. An immunohistochemical analysis showed that JMJD6 was highly expressed in the inflamed mucosa of esophageal tissues, esophageal carcinoma tissues, and atherosclerotic plaques. Hence, JMJD6 autoantibodies may reflect inflammation, thereby serving as a potential biomarker for diagnosing specific inflammation-related diseases, including stroke, AMI, DM, and cancers, and for prediction of the prognosis in patients with EC.
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Autoanticuerpos , Biomarcadores , Inflamación , Histona Demetilasas con Dominio de Jumonji , Humanos , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Biomarcadores/sangre , Inflamación/inmunología , Inflamación/sangre , Femenino , Histona Demetilasas con Dominio de Jumonji/inmunología , Histona Demetilasas con Dominio de Jumonji/metabolismo , Masculino , Persona de Mediana Edad , Neoplasias/inmunología , Neoplasias/diagnóstico , Neoplasias/sangre , Anciano , Adulto , Diabetes Mellitus/inmunología , Diabetes Mellitus/sangreRESUMEN
In this study, we propose a method for obtaining a new index to evaluate the resolution properties of computed tomography (CT) images in a task-based manner. This method applies a deep convolutional neural network (DCNN) machine learning system trained on CT images with known modulation transfer function (MTF) values to output an index representing the resolution properties of the input CT image [i.e., the resolution property index (RPI)]. Sample CT images were obtained for training and testing of the DCNN by scanning the American Radiological Society phantom. Subsequently, the images were reconstructed using a filtered back projection algorithm with different reconstruction kernels. The circular edge method was used to measure the MTF values, which were used as teacher information for the DCNN. The resolution properties of the sample CT images used to train the DCNN were created by intentionally varying the field of view (FOV). Four FOV settings were considered. The results of adapting this method to the filtered back projection (FBP) and hybrid iterative reconstruction (h-IR) images indicated highly correlated values with the MTF10% in both cases. Furthermore, we demonstrated that the RPIs could be estimated in the same manner under the same imaging conditions and reconstruction kernels, even for other CT systems, where the DCNN was trained on CT systems produced by the same manufacturer. In conclusion, the RPI, which is a new index that represents the resolution property using the proposed method, can be used to evaluate the resolution of a CT system in a task-based manner.
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Redes Neurales de la Computación , Tomografía Computarizada por Rayos X , Tomografía Computarizada por Rayos X/métodos , Algoritmos , Tomógrafos Computarizados por Rayos X , Fantasmas de Imagen , Procesamiento de Imagen Asistido por Computador/métodos , Dosis de RadiaciónRESUMEN
AIM: Whether sex differences exist in hereditary progeroid syndromes remains unclear. In this study, we investigated sex differences in patients with Werner syndrome (WS), a model of human aging, using patient data at the time of diagnosis. METHODS: The presence of six cardinal signs in the diagnostic criteria was retrospectively evaluated. RESULTS: We found that the percentage of patients with all cardinal signs was higher in males than in females (54.2% vs. 21.2%). By the age of 40 years, 57.1% of male patients with WS presented with all the cardinal signs, whereas none of the female patients developed all of them. In particular, the frequency of having a high-pitched, hoarse voice, a characteristic of WS, was lower in female patients. The positive and negative predictive values for clinical diagnosis were 100% for males and females, indicating the helpfulness of diagnostic criteria regardless of sex. More female patients than male (86.7% vs. 64%) required genetic testing for their diagnosis because their clinical symptoms were insufficient, suggesting the importance of genetic testing for females even if they do not show typical symptoms of WS. Finally, the frequency of abnormal voice was lower in patients with WS harboring the c.3139-1G > C homozygous mutation. CONCLUSION: These results indicate, for the first time, that there are sex differences in the phenotypes of hereditary progeroid syndromes. The analysis of this mechanism in this human model of aging may lead to the elucidation of sex differences in the various symptoms of normal human aging. Geriatr Gerontol Int 2024; 24: 161-167.
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Síndrome de Werner , Humanos , Masculino , Femenino , Síndrome de Werner/diagnóstico , Síndrome de Werner/genética , Estudios Retrospectivos , Caracteres Sexuales , Helicasa del Síndrome de Werner/genética , MutaciónRESUMEN
BACKGROUND: Autoantibodies develop in autoimmune diseases, cancer, diabetes mellitus (DM), and atherosclerosis-related diseases. However, autoantibody biomarkers have not been successfully examined for diagnosis and therapy. METHODS: Serological identification of antigens through recombinant cDNA expression cloning (SEREX) was used for primary screening of antigens. The cDNA product was expressed in bacteria and purified. Amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) was used to evaluate antibody levels in serum samples. RESULTS: Phosphoenolpyruvate carboxykinase 1 (PCK1) was recognized as an antigen by serum IgG antibodies in the sera of patients with atherosclerosis. AlphaLISA showed significantly higher serum antibody levels against recombinant PCK1 protein in patients with DM and cardiovascular disease than in healthy donors, but not in those with acute ischemic stroke, transient ischemic attack, or obstructive sleep apnea syndrome. The area under the receiver operating characteristic curve for anti-PCK1 antibodies was 0.7024 for DM. The serum anti-PCK1 antibody levels were associated with age, platelet count, and blood pressure. Anti-PCK1-antibody-positive patients showed significantly lower overall survival than the negative patients. CONCLUSIONS: Serum anti-PCK1 antibody levels were found to be associated with DM. The anti-PCK1 antibody marker is useful for predicting the overall survival of patients with DM.
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Aterosclerosis , Diabetes Mellitus , Accidente Cerebrovascular Isquémico , Humanos , ADN Complementario , Pronóstico , Diabetes Mellitus/diagnóstico , Autoanticuerpos , Proteínas Recombinantes , Fosfoenolpiruvato Carboxiquinasa (GTP) , Péptidos y Proteínas de Señalización IntracelularRESUMEN
Werner syndrome (WS) is a hereditary premature aging disorder characterized by visceral fat accumulation and subcutaneous lipoatrophy, resulting in severe insulin resistance. However, its underlying mechanism remains unclear. In this study, we show that senescence-associated inflammation and suppressed adipogenesis play a role in subcutaneous adipose tissue reduction and dysfunction in WS. Clinical data from four Japanese patients with WS revealed significant associations between the decrease of areas of subcutaneous fat and increased insulin resistance measured by the glucose clamp. Adipose-derived stem cells from the stromal vascular fraction derived from WS subcutaneous adipose tissues (WSVF) showed early replicative senescence and a significant increase in the expression of senescence-associated secretory phenotype (SASP) markers. Additionally, adipogenesis and insulin signaling were suppressed in WSVF, and the expression of adipogenesis suppressor genes and SASP-related genes was increased. Rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), alleviated premature cellular senescence, rescued the decrease in insulin signaling, and extended the lifespan of WS model of C. elegans. To the best of our knowledge, this study is the first to reveal the critical role of cellular senescence in subcutaneous lipoatrophy and severe insulin resistance in WS, highlighting the therapeutic potential of rapamycin for this disease.
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Resistencia a la Insulina , Insulinas , Lipodistrofia , Síndrome de Werner , Animales , Humanos , Síndrome de Werner/genética , Adipogénesis/genética , Caenorhabditis elegans , Senescencia Celular/genética , Grasa Subcutánea/metabolismo , Inflamación , Sirolimus , MamíferosRESUMEN
Aim: According to the current guidelines in Japan, the upper age limit for bariatric and metabolic surgery is 65 y. This study aimed to examine the appropriateness of this upper age limit. Methods: Using the database maintained by the Japanese Society for Treatment of Obesity, we conducted an analysis of patients in two age groups: those aged <65 y and those aged ≥65 y. Our analysis focused on postoperative weight loss, improvement in comorbidities, and frequency of perioperative complications. Results: A total of 2885 patients aged <65 y (mean, 43.9 ± 9.5 y) with a preoperative body mass index of 42.4 ± 8.1 kg/m2, while 56 aged ≥65 y (mean, 67.3 ± 3.2 y; maximum, 78 y) with a preoperative body mass index of 40.5 ± 6.6 kg/m2. Patients aged ≥65 y had a higher rate of dyslipidemia and hypertension. The rates of reoperation, surgical complications, and postoperative complications did not differ between the age groups. Both groups achieved significant weight loss postoperatively, and no differences in the improvement of comorbidities were noted. After adjusting the covariate balance via propensity score matching, no age-related differences in perioperative and postoperative complications were observed. Conclusion: Metabolic surgery is safe and effective for older patients with clinically severe obesity. Weight loss was less in patients aged ≥65 y, but the percentage of total weight loss did not differ between the groups.
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In addition to pathogenic autoantibodies, polyclonal autoantibodies with unknown physiological roles and pathogenicity are produced in the body. Moreover, serum antibodies against the proprotein convertase subtilisin/kexin type 9 (PCSK9) protein, which is integral to cholesterol metabolism, have also been observed. PCSK9 was also reported to be associated with insulin secretion and diabetes mellitus (DM). Therefore, we aimed to examine the clinical significance of PCSK9 antibodies (PCSK9-Abs) levels. We measured blood PCSK9-Abs and PCSK9 protein levels in 109 healthy donors (HDs) and 274 patients with DM (type 2 DM: 89.8%) using an amplified luminescence proximity homogeneous assay-linked immunosorbent assay. Subsequently, patients with DM were followed up (mean: 4.93 years, standard deviation: 2.77 years, maximum: 9.58 years, minimum: 0.07 years) to examine associations between antibody titers and mortality, myocardial infarction, stroke onset, and cancer. The primary endpoint of this study was to examine whether PCSK9-Abs can be a prognostic marker for overall mortality among the patients with diabetes. The secondary endpoint was to examine the relationship between PCSK9-Abs and clinical parameters. Although both PCSK9-Abs and PCSK9 protein levels were significantly higher in the DM group than in the HD group (p < 0.008), PCSK9-Abs and PCSK9 protein levels showed no correlation in either group. Mortality was significantly associated with higher PCSK9-Ab levels, but unrelated to PCSK9 protein levels. After investigating for potential confounding factors, higher PCSK9-Ab levels were still associated with increased mortality among the patients with DM. PCSK9-Abs may be a novel prognostic marker for overall mortality in patients with diabetes, and further studies are warranted to verify its usefulness.
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Diabetes Mellitus Tipo 2 , Proproteína Convertasa 9 , Humanos , Estudios Prospectivos , Diabetes Mellitus Tipo 2/complicaciones , Pronóstico , Autoanticuerpos , SubtilisinasRESUMEN
PURPOSE: Duplex ultrasound (DUS)-measured peak systolic velocity ratios (PSVRs) are commonly used to evaluate arterial stenosis in lower extremity artery disease (LEAD). However, these measurement methods have not yet been standardized. This study aimed to reveal the influence of measuring methods on PSVR values. METHODS: A 132 femoropopliteal lesions with PSVR ranging from 1.5 to 3.5 evaluated using method A (angle correction 60°, the direction of blood flow, the no or few atherosclerotic changes closest to the lesion proximal side was defined as the nonstenotic area) were included. The following 4 different methods were then compared with method A: method B, angle correction 45°; method C, angle correction 60° measured along the vessel wall; D, angle correction 60°, with the nonstenotic area the lowest peak systolic velocity area; and E, angle correction 60°, with the reference point fixed at 2 cm proximal to the target lesion area. The difference in PSVR values was analyzed using the Bland-Altman method. RESULTS: The mean PSVR value measured by method A was 2.27±0.51, those measured by methods B, C, D, and E were 2.21±0.55, 2.31±0.66, 2.34±0.63, and 2.11±0.63, respectively. The 95% prediction intervals of the differences in PSVR measurements versus A were -0.64 to +0.53 for method B, -0.59 to +0.68 for method C, -0.77 to +0.91 for method D, and -1.12 to +0.79 for method E. CONCLUSION: PSVR values considerably differed between measuring methods. PSVR values by DUS are largely dependent on the measurement methods, which could considerably affect the judgment of LEAD. CLINICAL IMPACT: Due to differences in several DUS measurement methods, the PSVR results could be changed. Therefore, to need further investigations and unification of measurement method.
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Úlcera Cutánea , Síndrome de Werner , Humanos , Senescencia Celular , Fibroblastos , Piel , Helicasa del Síndrome de WernerRESUMEN
Introduction: Autoantibodies against inflammatory cytokines may be used for the prevention of atherosclerosis. Preclinical studies consider colony-stimulating factor 2 (CSF2) as an essential cytokine with a causal relationship to atherosclerosis and cancer. We examined the serum anti-CSF2 antibody levels in patients with atherosclerosis or solid cancer. Methods: We measured the serum anti-CSF2 antibody levels via amplified luminescent proximity homogeneous assay-linked immunosorbent assay based on the recognition of recombinant glutathione S-transferase-fused CSF2 protein or a CSF2-derived peptide as the antigen. Results: The serum anti-CSF2 antibody (s-CSF2-Ab) levels were significantly higher in patients with acute ischemic stroke (AIS), acute myocardial infarction (AMI), diabetes mellitus (DM), and chronic kidney disease (CKD) compared with healthy donors (HDs). In addition, the s-CSF2-Ab levels were associated with intima-media thickness and hypertension. The analyzes of samples obtained from a Japan Public Health Center-based prospective study suggested the utility of s-CSF2-Ab as a risk factor for AIS. Furthermore, the s-CSF2-Ab levels were higher in patients with esophageal, colorectal, gastric, and lung cancer than in HDs but not in those with mammary cancer. In addition, the s-CSF2-Ab levels were associated with unfavorable postoperative prognosis in colorectal cancer (CRC). In CRC, the s-CSF2-Ab levels were more closely associated with poor prognosis in patients with p53-Ab-negative CRC despite the lack of significant association of the anti-p53 antibody (p53-Ab) levels with the overall survival. Conclusion: S-CSF2-Ab was useful for the diagnosis of atherosclerosis-related AIS, AMI, DM, and CKD and could discriminate poor prognosis, especially in p53-Ab-negative CRC.
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BACKGROUND AND OBJECTIVES: Red yeast rice contains monacolin K, an inhibitor of cholesterol synthesis, and gamma-aminobutyric acid, a neurotransmitter. The daily dose of red yeast rice and monacolin K in previous studies was relatively high; therefore, there were safety concerns. We aimed to examine the effects of low daily dose red yeast rice on arteriosclerosis in patients with mild dyslipidemia. METHODS AND STUDY DESIGN: Eighteen patients without known cardiovascular disease and unsatisfactory low-density lipoprotein cholesterol (3.96±0.19 mmol/L) controlled only by diet therapy were randomly allocated to receive low dose red yeast rice (200 mg/day) containing 2 mg monacolin K or diet therapy alone for 8 weeks. The primary outcome was the absolute change in low-density lipoprotein cholesterol. Secondary outcomes included total cholesterol, apolipoprotein B, and blood pressure. RESULTS: Low-density lipoprotein cholesterol decreased significantly in the red yeast rice group than in the diet therapy group (median [interquartile range]: control -0.20 [-0.62, 1.19] mmol/L vs. red yeast rice -0.96 [-1.05, -0.34] mmol/L, p=0.030). The red yeast rice group also exhibited significant decreases in total cholesterol, apolipoprotein B, and blood pressure. No severe treatment-related adverse effects on muscles, liver, or renal function were observed. CONCLUSIONS: We found that patients in the red yeast rice group exhibited significant reductions in lowdensity lipoprotein cholesterol, total cholesterol, apolipoprotein B, and blood pressure without any recognised adverse effect. This suggests that low daily dose red yeast rice could reduce cardiovascular risk in patients with dyslipidemia.
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Dislipidemias , Hipercolesterolemia , Productos Biológicos , Presión Sanguínea , LDL-Colesterol , Suplementos Dietéticos , Dislipidemias/tratamiento farmacológico , Humanos , Japón , LovastatinaRESUMEN
BACKGROUND: Paralytic shellfish toxins (PST) are a significant problem for the Tasmanian shellfish and Southern Rock Lobster (Jasus edwardsii) industries, and the introduction of a rapid screening test in the monitoring program could save time and money. OBJECTIVE: The aim was to perform a single-laboratory validation of the Neogen rapid test for PST in the hepatopancreas of Southern Rock Lobster. METHODS: The AOAC INTERNATIONAL guidelines for the validation of qualitative binary chemistry methods were followed. Three different PST profiles (mixtures) were used, of which two were commonly found in naturally contaminated lobster hepatopancreas (high in gonyautoxin 2&3 and saxitoxin), and the third toxin profile was observed in a few select animals (high in gonyautoxin 1&4). RESULTS: The Neogen test consistently returned negative results for non-target toxins (selectivity). The probability of detection (POD) of PST in the lobster hepatopancreas using the Neogen test increased with increasing PST concentrations. POD values of 1.0 were obtained at ≥0.57 mg STX-diHCl eq/kg in mixtures 1 and 2, and 0.95 and 1.0 for mixture 3 at 0.79 and 1.21 mg STX-diHCl eq/kg, respectively, with a fitted POD of 0.98 for 0.80 mg STX-diHCl eq/kg. The performance of the Neogen test when using four different production lots (ruggedness) showed no significant differences. CONCLUSIONS: The results of the validation study were satisfactory and the Neogen test is being trialed within the Tasmanian PST monitoring program of Southern Rock Lobster. HIGHLIGHTS: The Neogen rapid kit was successfully validated for the detection of PST in Southern Rock Lobster hepatopancreas.
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Laboratorios , Intoxicación por Mariscos , Animales , Inmunoensayo , Saxitoxina , Alimentos Marinos , Mariscos/análisisRESUMEN
In this study, we identified a previously uncharacterized skeletal satellite cell-secreted protein, R3h domain containing-like (R3hdml). Expression of R3hdml increases during skeletal muscle development and differentiation in mice. Body weight and skeletal muscle mass of R3hdml knockout (KO) mice are lower compared to control mice. Expression levels of cell cycle-related markers, phosphorylation of Akt, and expression of insulin-like growth factor within the skeletal muscle are reduced in R3hdml KO mice compared to control mice. Expression of R3hdml increases during muscle regeneration in response to cardiotoxin (CTX)-induced muscle injury. Recovery of handgrip strength after CTX injection was significantly impaired in R3hdml KO mice, which is rescued by R3hdml. Our results indicate that R3hdml is required for skeletal muscle development, regeneration, and, in particular, satellite cell proliferation and differentiation.
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Diferenciación Celular/genética , Células Satélite del Músculo Esquelético/citología , Células Satélite del Músculo Esquelético/metabolismo , Secuencia de Aminoácidos , Animales , Biomarcadores , Proliferación Celular , Expresión Génica , Perfilación de la Expresión Génica , Ratones , Ratones Noqueados , Desarrollo de Músculos/genética , Fibras Musculares Esqueléticas/citología , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Proteína MioD/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Regeneración , Transducción de SeñalRESUMEN
Mycotoxins are emerging toxins in the marine environment, which can co-occur with algal toxins to exert synergistic or antagonistic effects for human seafood consumption. The current study assesses the cytotoxicity of the algal toxin okadaic acid, shellfish, and dust storm-associated mycotoxins alone or in combination on human intestinal (HT-29) and neuroblastoma (SH-SY5Y) cell lines. Based on calculated IC50 (inhibitory concentration 50%) values, mycotoxins and the algal toxin on their own exhibited increased cytotoxicity in the order of sydowinin A < sydowinin B << patulin < alamethicin < sydowinol << gliotoxin ≈ okadaic acid against the HT-29 cell line, and sydowinin B < sydowinin A << alamethicin ≈ sydowinol < patulin, << gliotoxin < okadaic acid against the SH-SY5Y cell line. Combinations of okadaic acidâ»sydowinin A, â»alamethicin, â»patulin, and â»gliotoxin exhibited antagonistic effects at low-moderate cytotoxicity, but became synergistic at high cytotoxicity, while okadaic acidâ»sydowinol displayed an antagonistic relationship against HT-29 cells. Furthermore, only okadaic acidâ»sydowinin A showed synergism, while okadaic acidâ»sydowinol, â»alamethicin, â»patulin, and â»gliotoxin combinations demonstrated antagonism against SH-SY5Y. While diarrhetic shellfish poisoning (DSP) from okadaic acid and analogues in many parts of the world is considered to be a comparatively minor seafood toxin syndrome, our human cell model studies suggest that synergisms with certain mycotoxins may aggravate human health impacts, depending on the concentrations. These findings highlight the issues of the shortcomings of current regulatory approaches, which do not regulate for mycotoxins in shellfish and treat seafood toxins as if they occur as single toxins.
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Micotoxinas/toxicidad , Ácido Ocadaico/toxicidad , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Interacciones Farmacológicas , Humanos , Intestinos/citología , NeuroblastomaRESUMEN
Because growth hormone (GH) secretion is reportedly decreased in obese patients, we examined not only the factors associated with the decreased GH secretion but also GH response to the GH-releasing peptide (GHRP)-2-load test before and after laparoscopic gastrectomy (LSG). The study comprised 28 individuals aged 19-65 years [mean body mass index (BMI), 39.4 ± 9.4 kg/m2]. In the univariate analysis, GH secretion peaks correlated negatively with BMI (r = -0.59, p = 0.001), visceral adipose tissue (r = -0.47, p = 0.005), and subcutaneous adipose tissue (r = -0.40, p = 0.04). In the two obese patients, the response to the GHRP-2-load test markedly improved by weight loss 12 months after LSG. In conclusion, GH secretion was decreased in obese patients and improved by LSG.
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Gastrectomía/métodos , Obesidad/sangre , Obesidad/cirugía , Oligopéptidos/sangre , Adulto , Anciano , Femenino , Hormona Liberadora de Hormona del Crecimiento/sangre , Hormona Liberadora de Hormona del Crecimiento/metabolismo , Humanos , Laparoscopía , Masculino , Persona de Mediana Edad , Obesidad/metabolismo , Oligopéptidos/metabolismo , Estudios Retrospectivos , Adulto JovenRESUMEN
AIM: Laparoscopic sleeve gastrectomy (LSG) has proven to be the most effective strategy for the treatment of morbid obesity, however its efficacy and safety in an aging population has not yet been confirmed. In this study, we evaluated the effectiveness and safety of LSG in elderly obese Japanese patients. METHODS: Three obese individuals aged >60 years and 11 obese individuals aged <60 years who underwent LSG were enrolled. Pre- and postoperative changes after at least 12 months were examined, including bodyweight, body mass index, total weight loss, excess weight loss, bone mineral density and bone-related markers. RESULTS: There were no significant differences between patients aged <60 years and >60 years in terms of percent total weight loss (24.4 ± 11 vs 23 ± 4.4%, respectively) and percent excess weight loss (49.1 ± 23.4 vs 47.6 ± 10 %, respectively). Dual-energy X-ray absorptiometry was carried out before and 12 months after LSG. There were no significant differences in bone mineral density changes at the lumbar spine and femoral neck between the two groups (0.01 ± 0.06 vs 0.02 ± 0.03 g/cm2 , -0.03 ± 0.06 vs -0.08 ± 0.02 g/cm2 , respectively). There were no peri- and postoperative complications. All three patients aged >60 years had reduced bone mineral density in the femoral neck after LSG; one was diagnosed with osteoporosis. CONCLUSIONS: Although the present results suggest that LSG could be of considerable benefit to elderly obese Japanese patients, long-term careful observation after bariatric surgery is especially important in elderly patients to prevent future osteoporosis. Geriatr Gerontol Int 2017; 17: 2068-2073.
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Gastrectomía/métodos , Obesidad Mórbida/cirugía , Anciano , Humanos , Japón , Laparoscopía , Persona de Mediana Edad , Resultado del Tratamiento , Pérdida de PesoRESUMEN
Podocytes are essential for maintaining kidney glomerular functions. Injuries to podocyte are closely related to the pathological process of proteinuria. However, a treatment for podocyte injury has still not been established. Cilostazol (CSZ) and probucol (PBC) have been shown to possess renoprotective effects. Therefore, we evaluated these drugs in a lipopolysaccharide (LPS)-induced podocyte injury model. 7-week-old female C57BL/6J mice were fed a normal diet or a diet containing 0.3% CSZ, 0.5% PBC, or both for 10 days. Then, mice were intraperitoneally injected with 13 µg g-1 body weight LPS. Both CSZ and PBC decreased LPS-induced albuminuria and co-administration was found to be most effective. These treatments ameliorated the upregulation of monocyte chemoattractant protein 1. In cultured podocytes, CSZ suppressed LPS-induced activation of nuclear factor-kappa B (NF-κB) and phosphorylation of p44/42 mitogen-activated protein kinase (MAPK). PBC reduced LPS-induced activation of NF-κB and reactive oxygen species production. Furthermore, PBC decreased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase4 expression. Our findings suggest that CSZ and PBC are able to inhibit podocyte-injury through different mechanisms, indicating that a combination of these two old drugs is a good treatment option to protect podocytes from injury.
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Antiinflamatorios/farmacología , Antioxidantes/farmacología , Enfermedades Renales/prevención & control , Estrés Oxidativo/efectos de los fármacos , Podocitos/efectos de los fármacos , Probucol/farmacología , Tetrazoles/farmacología , Albuminuria/inducido químicamente , Albuminuria/metabolismo , Albuminuria/prevención & control , Animales , Células Cultivadas , Quimiocina CCL2/metabolismo , Cilostazol , Citoprotección , Modelos Animales de Enfermedad , Femenino , Enfermedades Renales/inducido químicamente , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Lipopolisacáridos , Ratones Endogámicos C57BL , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , NADPH Oxidasa 4/metabolismo , FN-kappa B/metabolismo , Fosforilación , Podocitos/metabolismo , Podocitos/patología , Transducción de Señal/efectos de los fármacosRESUMEN
Dust has been widely recognised as an important source of nutrients in the marine environment and as a vector for transporting pathogenic microorganisms. Disturbingly, in the wake of a dust storm event along the eastern Australian coast line in 2009, the Continuous Plankton Recorder collected masses of fungal spores and mycelia (~150,000 spores/m³) forming a floating raft that covered a coastal area equivalent to 25 times the surface of England. Cultured A. sydowii strains exhibited varying metabolite profiles, but all produced sydonic acid, a chemotaxonomic marker for A. sydowii. The Australian marine fungal strains share major metabolites and display comparable metabolic diversity to Australian terrestrial strains and to strains pathogenic to Caribbean coral. Secondary colonisation of the rafts by other fungi, including strains of Cladosporium, Penicillium and other Aspergillus species with distinct secondary metabolite profiles, was also encountered. Our bioassays revealed that the dust-derived marine fungal extracts and known A. sydowii metabolites such as sydowic acid, sydowinol and sydowinin A adversely affect photophysiological performance (Fv/Fm) of the coral reef dinoflagellate endosymbiont Symbiodinium. Different Symbiodinium clades exhibited varying sensitivities, mimicking sensitivity to coral bleaching phenomena. The detection of such large amounts of A. sydowii following this dust storm event has potential implications for the health of coral environments such as the Great Barrier Reef.