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关键词： Prostate Cancer   Metabolism based therapy   SM-88   AFRICAN-AMERICAN MEN   SURVIVAL   ANTIGEN  

摘要： BackgroundAndrogen deprivation therapy (ADT) is a standard treatment for high-risk biochemically-recurrent, non-metastatic prostate cancer (BRPC) but is not curative and associated with toxicity. Racemetyrosine (SM-88) is an amino-acid analogue used with methoxsalen, phenytoin, and sirolimus (MPS) to enhance SM-88 *** phase 1b/2, open-label trial in BRPC and rising PSA. Patients were given daily SM-88 (230 mg BID), methoxsalen (10 mg), phenytoin (50 mg), and sirolimus (0.5 mg)). Outcome measures included changes in PSA, circulating tumor cells (CTCs) and ***34 subjects were screened, 23 treated and 21 remained on study for >= 12 weeks. The median PSA was 6.4 ng/ml (range 1.7-80.1); doubling-time 6.2 months (range 1.4-36.6) and baseline testosterone 319.1 ng/ml (range 2.5-913.7). Median duration of therapy was 6.5 months (2.6-14.0). CTCs (median 48.5 cells/4 ml (range 15-268) at baseline) decreased a median of 65.3% in 18 of 19 patients. For patients who achieved an absolute CTC nadir count of <10 cells/4 ml (n = 10), disease control was 100% i.e. no metastases or PSA progression, while on trial (p = 0.005). PSA fell by >= 50% in 4.3% (1 subject). No patients developed metastatic disease while on treatment (metastases free survival =100%). There were no treatment-related adverse events (AEs) and quality of life was unchanged from baseline on the EORTC QLQ-C30 and QLQ-PR25. Testosterone levels rose slightly on SM-88 and were unrelated to efficacy or *** of SM-88 was associated with disease control while maintaining QOL. SM-88 may delay the need for ADT and the associated hormonal side effects. Larger trials are planned. Trial registration number, date of registration - NCT02796898, June 13, 2016

关键词： Acromegaly   GH   IGF-1   GLUCOSE-TOLERANCE TEST   GROWTH-FACTOR-I   QUALITY-OF-LIFE   ORAL GLUCOSE   IGF-I   DISEASE-ACTIVITY   HORMONE LEVELS   POSTOPERATIVE-PATIENTS   FOLLOW-UP   TEST OGTT  

摘要： Context Outcome of acromegaly surgery is assessed by IGF-1 and glucose-suppressed GH, but whether the latter provides additional clinically relevant information when IGF-1 is normal is unclear. The role of GH suppression testing after surgery requires clarification. Methods We studied 97 acromegaly patients with normal IGF-1 after surgery by measuring GH after oral glucose longitudinally, initially at >= 3 months after surgery and repeated one or more times >= 1 year later. Nadir GH was categorized as normal or abnormal relative to the 97.5th percentile of nadir GH in 100 healthy subjects, which were <= 0.14 mu g/L (DSL IRMA) or <= 0.15 mu g/L(IDS iSYS). Signs and symptoms scores and insulin resistance were followed longitudinally. Results Of 68 patients with initial normal GH suppression 63 (93%) remained in remission and of 29 with initial abnormal GH suppression, 9 (31%) recurred. Recurrence was more common in patients with abnormal suppression (P 0.001). A total of 14 patients recurred, including 5 with normal GH suppression progressing to abnormal and then recurrence. Overall, serial signs and symptoms and insulin resistance assessments did not identify patients with abnormal suppression or recurrence. Conclusion Risk of recurrence after surgery is increased for patients with a normal IGF-1 level, but abnormal GH suppression. We newly find, using both our and others' cut-offs, that while normal suppression predicts long-term remission in most patients, some can progress from normal to abnormal suppression and then recurrence after many years of follow up. Nadir GH levels are of prognostic value in acromegaly patients with normal IGF-1 levels after surgery.

关键词： Radical prostatectomy   Biochemical recurrence   Radiation therapy   Androgen deprivation therapy   Salvage   RADIOTHERAPY   CANCER   SURVIVAL   ANTIGEN   MEN   FAILURE   UPDATE  

摘要： Background The salvage treatments for biochemical recurrence (BCR) include local external beam radiation therapy (RT) and systemic androgen-deprivation therapy (ADT). Methods We reviewed patients who underwent radical prostatectomy (RP) and developed BCR at three institutions. After excluding patients whose nadir prostate-specific antigen (PSA) was higher than 0.2 ng/mL, those who received neoadjuvant/adjuvant therapy, and those whose BCR was not treated until their PSA exceeded 4.0 ng/mL, the remaining 335 patients comprised the cohort of this study. Salvage RT and ADT were performed for 154 and 181 patients, respectively. After the failure of salvage RT, all patients received subsequent ADT. The starting point of this study was the timing of BCR and the endpoint was the development of castration-resistant prostate cancer (CRPC). Results During the mean follow-up period of 8.5 years after BCR, CRPC was observed in 13 patients administered RT and 24 patients administered ADT. Kaplan-Meier curves demonstrated no significant difference in CRPC-free survival between the RT and ADT groups (10-year CRPC-free survival 89.9 vs. 86.3%, p = 0.199). On the other hand, we found a significant difference in CRPC-free survival between the RT and ADT groups in 50 high-risk patients with two risk factors of Grade Group >= 4 and PSA-doubling time < 6 months (10-year CRPC-free survival 73.4 vs. 40.3%, p = 0.040). Conclusion This study revealed that salvage RT increases the CRPC-free survival rate compared with salvage ADT in high-risk patients with Grade Group >= 4 and PSA-doubling time < 6 months.

关键词： a食品微生物  

ISBN: (纸本)9787521911190

关键词： Se-enriched rice   Inorganic selenium   Cadmium poisoning mice   Antioxidation   Relative gene expression   HEPATIC LIPID-PEROXIDATION   OXIDATIVE STRESS   GLUTATHIONE-PEROXIDASE   MESSENGER-RNA   SELENIUM   TOXICITY   SELENOPROTEIN   ANTIOXIDANT   METABOLISM   EXCRETION  

摘要： Cadmium (Cd) is an element injurious for human health and is possibly toxic to organisms at minor concentrations. While some of other trace metallic elements have antagonistic features to it. One of them is the interaction between selenium (Se) and Cd in plant different organs. Literature review disclosed that the intake of Se to some extent can reduce the accumulation of Cd in plants, while the research on of trace metallic elements (Cd) and Se-enriched food (rice) in the living body has rarely been reported. This study intended to explore whether there was a mitigating effect of Se-enriched rice on mice poisoned with Cd. A mouse model of low-dose and high-dose Cd poisoning was established (supplemented with cadmium chloride(CdCl2 center dot 21/2H(2)0)), followed by feeding two groups (1) Se-enriched rice and (2) setting an equal amount of inorganic Se group. After that, the impact of Se-enriched rice on the antioxidant activity was evaluated. The Se-enriched diet enhanced the total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and enzyme activities of GSH peroxidase (GSH-Px) in mice livers and kidney whereas significantly decreased the malondialdehyde (MDA) contents. Moreover, the degree of physiological damage in mice with low cadmium poisoning was significantly alleviated, and the expression of antioxidant genes (Nrf-2, GPX1, TrxR2, TNF-2) was increased. In conclusion, the Se-enriched diet has a positive effect on the biological effects in mice, and it can be used as a daily diet to resist damage to the body's low Cd state and support enzymatic antioxidant systems by eliminating oxidative injury.

关键词： Parkinson’s disease   LRRK2   GBA   Glomerular filtration rate   Renal functions   PROTEINURIA   EPIDEMIOLOGY   MUTATIONS   RATIO   INFLAMMATION   ASSOCIATION   DYSFUNCTION   PREDICTION  

摘要： Background The phenotype of Parkinson's disease (PD) is variable with mutations in genes such as LRRK2 and GBA explaining part of this heterogeneity. Additional genetic and environmental factors contribute to disease variability. Objective To assess the association between biochemical markers, PD severity and probability score for prodromal PD, among GBA and LRRK2 mutation carriers. Methods Levels of uric acid, vitamin D, C-reactive protein, microalbumin/creatinine ratio (ACR), white blood count (WBC), hemoglobin, platelets, neutrophil/lymphocyte ratio and estimated glomerular filtration rate (eGFR) were assessed from patients with PD and non-manifesting carriers (NMC) of mutations in GBA and LRRK2, together with disease related questionnaires enabling the construction of the MDS prodromal probability score. Result A total of 241 patients with PD: 105 idiopathic PD (iPD), 49 LRRK2-PD and 87 GBA-PD and 412 non-manifesting subjects; 74 LRRK2-NMC, 118 GBA-NMC and 220 non-manifesting non-carriers (NMNC), participated in this study. No significant differences in biochemical measures were detected among patients with PD or non-manifesting carriers. Among GBA-PD patients, worse motor performance was associated with ACR (B = 4.68, 95% CI (1.779-7.559); p = 0.002). The probability score for prodromal PD among all non-manifesting participants was associated with eGFR; NMNC (B = - 0.531 95% CI (- 0.879 to - 0.182); p < 0.001, LRRK2-NMC (B = - 1.014 95% CI (- 1.663 to - 0.366); p < 0.001) and GBA-NMC (B = - 0.686 95% CI (1.300 to - 0.071); p = 0.029). Conclusion Sub-clinical renal impairment is associated with increased likelihood for prodromal PD regardless of genetic status. While the mechanism behind this finding needs further elucidation, it suggests that kidney function might play a role in PD pathogenesis.

摘要： Purpose Device 1 [Impella 5.5 (Abiomed, Danvers MA, USA)] is the upgraded micro-axial, forward flow ventricular assist device (LVAD) developed for treatment of cardiogenic shock and provides a novel 6.2 L/min flow. Our institution was among the few selected for FDA pre-market use of Device 1. Here we compare 1) hemodynamic performance and 2) the subsequent impact on organ perfusion between Device 1 and the previous model: Device 2 [Impella 5.0]. Methods Single center, retrospective analysis included all patients who underwent Device 2 (n=37) and Device 1 (n=11) implantation July 2012 - June 2020. Preimplant baseline hemodynamic and biochemical data were compared at 24 and 72 hours post-implantation and are presented as delta values in Figure 1. Population mean and median values for individual parameters, as well as the delta values for each device, are reported for hemodynamic and biochemical data, respectively. Statistical significance was assessed with a Student's T test; a p value of ≤ 0.05 conferred significance. Results Both devices demonstrated improvement in measured parameters after implantation especially at 24 hours post-implantation (Figure 2). The trajectory of the measured hemodynamic data was nearly identical between both groups without any statistically significant difference. Conclusion In our study, both groups were provided similar hemodynamic support and successfully reversed cardiogenic shock as evidenced by correction of biochemical parameters indicative of improvement in tissue perfusion. Larger studies are warranted to know more benefits of this new technology.

关键词： zebra mussel   abundance and biomass   size structure   distribution   chorological types   trace element composition of shells   DIVERSITY   MOLLUSK  

摘要： In June 2017, the invasion of an alien species Dreissena polymorpha was recorded in one of the quarries located in the Lake Ladoga basin (the Kelkolovo quarries, Kirovsky district, Leningrad Region). The biology of the population and the trace element composition in shells of the mollusks were studied. It is found that the population is young with a high potential for further development under favorable environmental conditions. One of the prerequisites for invasion of the species into the water body is a high water mineralization, which provides an optimum level of elements necessary for the construction of a calcareous skeleton of a large number of specimens. The main chorological types formed by zebra mussels are brushes and druses which allow the maximum use of food resources in a limited space. The role of shells in accumulation and bio-burial of some trace elements is shown.

关键词： Metals   Bivalves   Enzymes   GlutathioneS-Transferase   Catalase  

摘要： This study aimed to compare biochemical and histological biomarkers in oysters to identify impacted areas in a Brazilian port region. Oysters belonging to the Crassostrea genus were collected in two points in Sao Jose Bay (Brazil): (A1) Curupu Island (control area) and (A2) Braga Port (impacted area). Digestive glands from oysters were used to analyze the enzymatic activity of glutathione S-transferase and Catalase. The gills were used for standard histology analyses. Water samples were collected for metal analyses. Our results indicated that there was a change in the activity of oyster GST and CAT enzymes, especially in A2. Histological gill analysis indicated more frequent changes in A2. The analyzed metals presented higher values in A2. The results of this study suggest that enzymatic alterations, histological changes and higher metal values are indicative of initial stress caused by contaminants in Sao Jose Bay, especially in the port region.