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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.
994.
Infections with hepatitis C virus (HCV) represent a substantial national and international public health burden. HCV has been associated with numerous extrahepatic conditions and can lead to metabolic derangements that are associated with atherosclerosis and cardiovascular disease. We investigated whether HCV infection is associated with an increased number of acute coronary syndrome (ACS) events among hospitalized patients in an inner-city tertiary hospital.We performed a matched (age, sex, and race/ethnicity) case-control study on patients at least 18 years old admitted to inpatient medical and cardiac services at the University of Maryland Medical Center from 2015 through 2018. The primary outcome was ACS and the primary exposure was HCV infection. Covariates of interest included: alcohol use, tobacco use, illicit drug use, hypertension, diabetes mellitus, human immunodeficiency virus infection, body mass index, dyslipidemia, and family history of coronary heart disease. Covariates with significant associations with both exposure and outcome in bivariate analyses were included in the multivariable analyses of the final adjusted model.There were 1555 cases and 3110 controls included in the final sample. Almost 2% of cases and 2.4% of controls were HCV infected. In adjusted models, there was no significant association found between experiencing an ACS event in those with HCV infection compared to those without HCV infection (odds ratio 0.71, 95% confidence interval 0.45–1.11).We found no significant association between HCV infection and ACS in our study population. However, given the mixed existing literature, the association between HCV and ACS warrants further investigation in future prospective cohort and/or interventional studies. 相似文献
995.
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
996.
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
997.
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
998.
999.
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
1000.
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