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SC79 promotes efficient entry of GDNF liposomes into brain parenchyma to repair dopamine neurons through reversible regulation of tight junction proteins

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Nano Research 2023年第2期16卷 2695-2705页

作者： Xiaomei Wu Li Wang Kai Wang Jia Ke Sufen Li Tingting Meng Hong Yuan Qirui Zhang Fuqiang Hu College of Pharmaceutical Science Zhejiang UniversityHangzhou 310058China College of Pharmaceutical Science Shenyang Pharmaceutical UniversityShenyang 110016China

Glial cell line-derived neurotrophic factor(GDNF),a disease-modifying drug for Parkinson’s disease(PD)is in Phase 2 clinical trials(EudraCT number:2011-003866-34),however it is administered by direct intrastriatal delivery via stereotaxy,which is accompanied with intracranial infection,brain tissue damage,and other complications.In addition,because of complex administration routes,clinical trials of GDNF have yielded contrary results,largely due to differences in dose and concentration brought by intracranial device.Herein,a small molecular agonist SC79 was screened to open blood-brain barrier(BBB)and promote GDNF liposomes to get into brain.SC79 reversibly reduces the expression of claudin-5,one of dominant tight junctions of BBB.Animal study showed SC79 promoted liposomes to enter into brain parenchyma 2.43 times more than that of the control.Motor deficits of PD mice receiving SC79 and brain-targeted GDNF liposomes were recovered by 36.70%and tyrosine hydroxylase positive neurons in striatum were restored by 39.90%.Our combination therapy effectively avoids the side effects such as secondary infection and uneven delivery caused by intracranial injection,improving patients’compliance and providing valuable research ideas for the clinic.

关键词： blood-brain barrier brain delivery facilitation tight junction glial cell line-derived neurotrophic factor disease-modifying Parkinson’s disease

Precautions before starting tofacitinib in persons with rheumatoid arthritis

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World Journal of Clinical Cases 2022年第36期10卷 13467-13469页

作者： Raktim Swarnakar Shiv Lal Yadav Department of Physical Medicine and Rehabilitation All India Institute of Medical SciencesNew DelhiNew Delhi 11049DelhiIndia

Tofacitinib is an immunosuppressive and disease-modifying therapy in rheumatoid arthritis.It may result in many infections flaring up.It is important to take precautions of all kinds(cardiovascular,malignancy,infections etc.)before starting tofacitinib.In this article,we have highlighted important steps where we need to take precautions before starting tofacitinib.

关键词： Tofacitinib Rheumatoid arthritis DMARDs disease-modifying Precaution Side-effects

State-of-the-Art management of knee osteoarthritis

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World Journal of Clinical Cases 2015年第2期3卷 89-101页

作者： Kenton H Fibel Howard J Hillstrom Brian C Halpern Department of Medicine Primary Care Sports MedicineHospital for Special Surgery Leon Root Motion Analysis Laboratory Department of RehabilitationHospital for Special Surgery

Osteoarthritis(OA) is the most common type of arthritis found in the United States' population and is also the most common disease of joints in adults throughout the world with the knee being the most frequently affected of all joints. As the United States' population ages along with the increasing trends in obesity prevalence in other parts of the world, it is expected that the burden of OA on the population, healthcare system, and overall economy will continue to increase in the future without making major improvements in managing knee OA. Numerous therapies aim to reduce symptoms of knee OA and continued research has helped to further understand the complex pathophysiology of its disease mechanism attempting to uncover new potential targets for the treatment of OA. This review article seeks to evaluate the current practices for managing knee OA and discusses emerging therapies on the horizon. These practices include non-pharmacological treatments such as providing patient education and self-management strategies, advising weight loss, strengthening programs, and addressing biomechanical issues with bracing or foot orthoses. Oral analgesics and anti-inflammatories are pharmacologicals that are commonly used and the literature overall supports that some of these medications can be helpful for managing knee OA in the short-term but are less effective for long-term management. Additionally, more prolonged use significantly increases the risk of serious associated side effects that are not too uncommon. diseasemodifying osteoarthritis drugs are being researched as a treatment modality to potentially halt or slow disease progression but data at this time is limited and continued studies are being conducted to further investigate their effectiveness. Intra-articular injectables are also implemented to manage knee OA ranging from corticosteroids to hyaluronans to more recently plateletrich plasma and even stem cells while several other injection therapies are presently being studied. The goal of developing new treatme

关键词： disease-modifying osteoarthritis drugs Knee osteoarthritis disease-modifying osteoarthritis drugs Osteoarthritis management Non-steroidal antiinflammatory drugs Hyaluronic acid Arthroscopy Platelet-rich plasma Corticosteroids Stem cells

Management of psoriasis patients with hepatitis B or hepatitis C virus infection

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World Journal of Gastroenterology 2016年第28期22卷 6444-6455页

作者： Claudio Bonifati Viviana Lora Dario Graceffa Lorenzo Nosotti Center for the Study and Treatment of Psoriasis San Gallicano Dermatologic Institute IRCCS Gastrointestinal and Liver Department National Institute for Health Migration and Poverty

The systemic therapies available for the management of Psoriasis(PsO) patients who cannot be treated with more conservative options, such as topical agents and/or phototherapy, with the exception of acitretin, can worsen or reactivate a chronic infection. Therefore, before administering immunosuppressive therapies with either conventional disease-modifying drugs(c DMARDs) or biological ones(b DMARDs) it is mandatory to screen patients for some infections, including hepatitis B virus(HBV) and hepatitis C virus(HCV). In particular, the patients eligible to receive an immunosuppressive drug must be screened for the following markers: antibody to hepatitis B core, antibody to hepatitis B surface antigen(anti-HBs Ag), HBs Ag, and antibody to HCV(anti-HCV). In case HBV or HCV infection is diagnosed, a close collaboration with a consultant hepatologist is needed before and during an immunosuppressive therapy. Concerning therapy with immunosuppressive drugs in PsO patients with HBV or HCV infection, data exist mainly for cyclosporine a(Cy A) or b DMARDs(etanercept, adalimumab, infliximab, ustekinumab). The natural history of HBV and HCV infection differs significantly as well as the effect of immunosuppression on the aforementioned infectious diseases. As a rule, in the case of active HBV infection, systemic immunosuppressive antipsoriatic therapies must be deferred until the infection is controlled with an adequate antiviral treatment. Inactive carriers need to receive antiviral prophylaxis 2-4 wk before starting immunosuppressive therapy, to be continued after 6-12 mo from its suspension. Due to the risk of HBV reactivation, these patients should be monitored monthly for the first 3 mo and then every 3 mo for HBV DNA load together with transaminases levels. Concerning the patients who are occult HBV carriers, the risk of HBV reactivation is very low. Therefore, these patients generally do not need antiviral prophylaxis and the sera HBs Ag and transaminases dosing can be monitored every 3 mo. Concerning PsO patients wit

关键词： Psoriasis Therapy Conventional disease modifying drugs Biological disease-modifying drugs Hepatitis

Treatment strategies for multiple sclerosis:When to start,when to change,when to stop?

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World Journal of Clinical Cases 2015年第7期3卷 545-555页

作者： Alberto Gajofatto Maria Donata Benedetti Department of Neurological and Movement Sciences University of Verona Regional Center for Multiple Sclerosis Unit of NeurologyPoliclinico Borgo RomaAzienda Ospedaliera Universitaria Integrata Verona

Multiple sclerosis(MS) is a chronic inflammatory condition of the central nervous system determined by a presumed autoimmune process mainly directed against myelin components but also involving axons and neurons. Acute demyelination shows as clinical relapses that may fully or partially resolve, while chronic demyelination and neuroaxonal injury lead to persistent and irreversible neurological symptoms, often progressing over time. Currently approved disease-modifying therapies are immunomodulatory or immunosuppressive drugs that significantly although variably reduce the frequency of attacks of the relapsing forms of the disease. However, they have limited efficacy in preventing the transition to the progressive phase of MS and are of no benefit after it has started. It is therefore likely that the potential advantage of a given treatment is condensed in a relatively limited window of opportunity for each patient, depending on individual characteristics and disease stage, most frequently but not necessarily in the early phase of the disease. In addition, a sizable proportion of patients with MS may have a very mild clinical course not requiring a disease-modifying therapy. Finally, individual response to existing therapies for MS varies significantly across subjects and the risk of serious adverse events remains an issue, particularly for the newest agents. The present review is aimed at critically describing current treatment strategies for MS with a particular focus on the decision of starting, switching and stopping commercially available immunomodulatory and immunosuppressive therapies.

关键词： Multiple sclerosis disease-modifying therapy Treatment start Treatment switch Treatment stop Interferon beta Glatiramer acetate Azathioprine Natalizumab Fingolimod

Use of biologic agents for rheumatic diseases in pregnancy

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World Journal of Rheumatology 2015年第2期5卷 50-58页

作者： Yesim Garip Department of Physical Medicine and Rehabilitation Department of Physical Medicine and Rehabilitation Pinar Physical Therapy and Rehabilitation Center

Biologic agents have ushered a new era in the treatment of inflammatory rheumatic diseases.In recent years,several biologic agents have been approved by food and drug administration and have significantly improved outcomes for patients with immune mediatedinflammatory disorders including rheumatic and inflammatory bowel diseases.The most common used biologic therapeutic agents are tumor necrosis factor inhibitors(etanercept,infliximab,adalimumab,certolizumab pegol,and golimumab),an interleukin(IL)-6 inhibitor(tocilizumab),an IL-1 receptor antagonist(anakinra),an anti-CD-20 antibody(rituximab),and a T cell costimulation modulator(abatacept).Their use during pregnancy has been controversial because of absence of controlled studies which have enrolled pregnant women.This brief overview provides published data on use of biologic agents for the treatment of rheumatic diseases in pregnancy.

关键词： Ankylosing spondylitis Rheumatoid arthritis Pregnancy disease-modifying antirheumatic drugs