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991.
Yuki Kato Masayuki Ninomiya Yuji Yamaguchi Mamoru Koketsu 《Medicinal chemistry research》2015,24(3):1180-1188
Hyaluronidase is one of the most important enzymes in the development of many diseases. In this study, a series of xyloside analogues bearing a triazole and tetrazole at the anomeric position were prepared from xylosylthioureas and evaluated their inhibitory effects on the hyaluronidase. Triazole and tetrazole skeletons were formed via the Hg(OAc)2-mediated desulfurizative cyclization through carbodiimide intermediates. According to in vitro anti-hyaluronidase assay, tetrazole-xylosides having p-chloro- or p-nitro-substitution exhibited the high inhibition rates, whereas the compound having p-trifluoromethyl group on the structure did not show the potency. Our results demonstrated the importance of tetrazole-xylosides as hyaluronidase inhibitors. 相似文献
992.
Gadi G. Bornstein 《The AAPS journal》2015,17(3):525-534
The development path for antibody drug conjugates (ADCs) is more complex and challenging than for unmodified antibodies. While many of the preclinical considerations for both unmodified and antibody drug conjugates are shared, special considerations must be taken into account when developing an ADC. Unlike unmodified antibodies, an ADC must preferentially bind to tumor cells, internalize, and traffic to the appropriate intracellular compartment to release the payload. Parameters that can impact the pharmacological properties of this class of therapeutics include the selection of the payload, the type of linker, and the methodology for payload drug conjugation. Despite a plethora of in vitro assays and in vivo models to screen and evaluate ADCs, the challenge remains to develop improved preclinical tools that will be more predictive of clinical outcome. This review will focus on preclinical considerations for clinically validated small molecule ADCs. In addition, the lessons learned from Mylotarg®, the first in class FDA-approved ADC, are highlighted. 相似文献
993.
Khan Sara Shridharmurthy Divya Lapane Kate L. Dube Catherine Kay Jonathan Yi Esther Liu Shao-Hsien 《Clinical rheumatology》2022,41(4):1115-1124
Clinical Rheumatology - Axial spondyloarthritis (axSpA) affects patients’ health-related quality of life (HRQoL). Prior studies have documented gender differences in axSpA across the disease... 相似文献
994.
Alexandru Hanganu Stanislav A. Groppa Günther Deuschl Hartwig Siebner Friederike Moeller Michael Siniatchkin Ulrich Stephani Sergiu Groppa 《Brain topography》2015,28(5):702-709
Photoparoxysmal response (PPR) is an EEG trait of spike and spike-wave discharges in response to photic stimulation that is closely linked to idiopathic generalized epilepsy (IGE). In our previous studies we showed that PPR is associated with functional alterations in the occipital and frontal cortices. The aim of the present study was to determine structural changes associated with PPR. For this purpose we analysed the cortical thickness as derived from T1 MRI images in PPR-positive-subjects (n = 12; 15.5 ± 8.6 years; 4 males), PPR-positive-IGE-patients (n = 12; 14.9 ± 2.7 years; 4 males) and compared these groups with a group of PPR-negative-healthy-controls (HC, n = 17; 15.3 ± 3.6 years; 6 males). Our results revealed an increase of cortical thickness in the occipital, frontal and parietal cortices bilaterally in PPR-positive-subjects in comparison to HC. Moreover PPR-positive-subjects presented a significant decrease of cortical thickness in the temporal cortex in the same group contrast. IGE patients exhibited lower cortical thickness in the temporal lobe bilaterally and in the right paracentral region in comparison to PPR-positive-subjects. Our study demonstrates structural changes in the occipital lobe, frontoparietal regions and temporal lobe, which also show functional changes associated with PPR. Patients with epilepsy present changes in the temporal lobe and supplementary motor area. 相似文献
995.
Emy Hiura Aline del Carmen Garcia Lopes Jeanne Saraiva da Paz Maylla Garschagen Gava Mayra Cunha Flecher Manuela Colares Filippe Elias de Freitas Soares Leandro Abreu da Fonseca Tracy Lacerda Jackson Victor de Araújo Fabio Ribeiro Braga 《Parasitology research》2015,114(9):3301-3308
The objective of this study was to evaluate the infectivity of Toxocara canis eggs after interacting with isolated nematophagous fungi of the species Duddingtonia flagrans (AC001) and Pochonia chlamydosporia (VC4), and test the predatory activity of the isolated AC001 on T. canis second stage larvae after 7 days of interaction. In assay A, 5000 embryonated T. canis eggs previously in contact with the AC001 and VC4 isolated for 10 days were inoculated into domestic chickens (Gallus gallus domesticus), and then these animals were necropsied to collect material (digested liver, intestine, muscles and lungs) at 3-, 7-, 14-, and 21-day intervals after inoculation. In assay A, the results demonstrated that the prior interaction of the eggs with isolated AC001 and VC4 decreases the amount of larvae found in the collected organs. Difference (p?<?0.01) was observed in the medium larvae counts recovered from liver, lung, intestine, and muscle of animals in the treated groups when compared to the animals in the control group. At the end of assay A, a percentage reduction of 87.1 % (AC001) and 84.5 % (VC4) respectively was recorded. In the result of assay B, the isolated AC001 showed differences (p?<?0.01) compared to the control group, with a reduction of 53.4 % in the recovery of L2. Through these results, it is justified to mention that prior interaction of embryonated T. canis eggs with the tested fungal isolates were efficient in reducing the development and migration of this parasite, in addition to the first report of proven predatory activity on L2. 相似文献
996.
João Dallyson Sousa de Almeida Aristófanes Corrêa Silva Jorge Antonio Meireles Teixeira Anselmo Cardoso Paiva Marcelo Gattass 《Journal of digital imaging》2015,28(4):462-473
Strabismus is a pathology that affects approximately 4 % of the population, causing aesthetic problems reversible at any age and irreversible sensory alterations that modify the vision mechanism. The Hirschberg test is one type of examination for detecting this pathology. Computer-aided detection/diagnosis is being used with relative success to aid health professionals. Nevertheless, the routine use of high-tech devices for aiding ophthalmological diagnosis and therapy is not a reality within the subspecialty of strabismus. Thus, this work presents a methodology to aid in diagnosis of syndromic strabismus through digital imaging. Two hundred images belonging to 40 patients previously diagnosed by an specialist were tested. The method was demonstrated to be 88 % accurate in esotropias identification (ET), 100 % for exotropias (XT), 80.33 % for hypertropias (HT), and 83.33 % for hypotropias (HoT). The overall average error was 5.6Δ and 3.83Δ for horizontal and vertical deviations, respectively, against the measures presented by the specialist. 相似文献
997.
998.
The etiology of system lupus erythematosus (SLE) still remains unclear, and vitamin D is associated with immune response. Although a few studies are conducted to investigate the association between polymorphism in vitamin D receptor (VDR) genes and SLE risk, their results are conflicting. Following the guideline of PRISMA, we conducted a systematic search and meta-analysis of the BsmI polymorphism rs1544410 and the risk of SLE. The pooled odds ratios (OR) and its 95 % confidential interval (CI) were calculated by using Stata Version 10 with dominant and recessive model and allele analyses. Nine studies were included in our meta-analysis with a total of 1247 SLE cases and 1687 controls. No significant association was found in both models in the overall population. Only Bb?+?BB genotypes showed a significantly elevated SLE risk in Asian subgroup with an OR of 3.26 (95 % CI?=?1.30–8.17) while no significance was observed in Caucasian population. Notably, B allele significantly increased the SLE risk among Asian population with an OR of 2.29 (95 % CI?=?1.14–4.61). No positive findings were reported in Caucasian population and in the overall analysis. In Asian population, Bb?+?BB genotype and B allele can significantly increase the SLE risk. 相似文献
999.
Tess Petersen Kerry Townsend Lori A. Gordon Sreetha Sidharthan Rachel Silk Amy Nelson Chloe Gross Monica Calderón Michael Proschan Anu Osinusi Michael A. Polis Henry Masur Shyam Kottilil Anita Kohli 《Hepatology International》2016,10(2):310-319
Background
As treatment for chronic hepatitis C (HCV) virus has evolved to all-oral, interferon-free directly acting antiviral (DAA) therapy, the impact of these improvements on patient adherence has not been described.Methods
Medication adherence was measured in 60 HCV, genotype-1, treatment-naïve participants enrolled in a phase 2a clinical trial at the National Institutes of Health and community clinics. Participants received either ledipasvir/sofosbuvir (LDV/SOF) (90 mg/400 mg) (one pill) daily for 12 weeks, LDV/SOF + GS-9451 (80 mg/day) (two pills) daily for 6 weeks, or LDV/SOF + GS-9669 (500 mg twice daily; three pills, two in the morning, one in the evening) for 6 weeks. Adherence was measured using medication event monitoring system (MEMS) caps, pill counts and patient report.Results
Overall adherence to DAAs was high. Adherence declined over the course of the 12-week treatment (p = 0.04). While controlled psychiatric disease or symptoms of depression did not influence adherence, recent drug use was a risk factor for non-adherence to 12-week (p = 0.01), but not 6-week regimens. Adherence as measured by MEMS was lower than by patient report.Conclusions
Adherence to short courses of DAA therapy with 1–3 pills a day was excellent in an urban population with multiple risk factors for non-adherence.1000.
Abstract Currently available anticoagulants are effective in reducing the recurrence rate of venous thromboembolism (VTE). However,
anticoagulant treatment is associated with an increased risk for bleeding complications. Thus, anticoagulation has to be discontinued
when benefit of treatment no longer clearly outweigh its risks. The duration of anticoagulant treatment is currently framed
based on the estimated individual risk for recurrent VTE. The incidence of recurrent VTE can be estimated through a two-step
decision algorithm. Firstly, the features of the patient (gender), of the initial event (proximal or distal deep vein thrombosis
or pulmonary embolism), and the associated conditions (cancer, surgery, etc) provide essential information on the risk for
recurrence after anticoagulant treatment discontinuation. Secondly, at time of anticoagulant treatment discontinuation, d-dimer levels and residual thrombosis have been indicated as predictors of recurrent VTE. Current evidence suggests that the
risk of recurrence after stopping therapy is largely determined by whether the acute episode of VTE has been effectively treated
and by the patient’s intrinsic risk of having a new episode of VTE. All patients with acute VTE should receive oral anticoagulant
treatment for three months. At the end of this treatment period, physicians should decide for withdrawal or indefinite anticoagulation.
Based on intrinsic patient’s risk for recurrent VTE and for bleeding complications and on patient preference, selected patients
could be allocated to indefinite treatment with VKA with scheduled periodic re-assessment of the benefit from extending anticoagulation.
Alternative strategies for secondary prevention of VTE to be used after conventional anticoagulation are currently under evaluation.
Cancer patients should receive low molecular-weight heparin over warfarin in the long-term treatment of VTE. These patients
should be considered for extended anticoagulation at least until resolution of underlying disease.
Abbreviated abstract The risk for recurrent venous thromboembolism can be estimated through a two-step algorithm. Firstly, the features of the
patient (gender), of the initial event (proximal or distal deep vein thrombosis or pulmonary embolism), and the associated
conditions (cancer, surgery, etc) are essential to estimate the risk for recurrence after anticoagulant treatment discontinuation.
Secondly, a correlation has been shown between d-dimer levels and residual thrombosis at time of anticoagulant treatment discontinuation and the risk of recurrence. Currently
available anticoagulants are effective in reducing the incidence of recurrent venous thromboembolism, but they are associated
with an increased risk for bleeding complications. All patients with acute venous thromboembolism should receive oral anticoagulant
treatment for three months. At the end of this treatment period physicians should decide for definitive withdrawal or indefinite
anticoagulation with scheduled periodic re-assessment of the benefit from extending anticoagulation. 相似文献