Current therapy for recurrent and extensive anal warts

SummaryCurrent therapy for hemophilia B requires large intravenous doses of factor IX (F.IX) given in the clinic or at home. Although home therapy is possible for many patients, it is often complicated by factors such as the lack of good venous access. Very little is known about extravascular routes for administering proteins like F.IX (57 kD) or other vitamin K-dependent procoagulant factors into the circulation. Questions about the absorption rate from extravascular administration as well as plasma recovery and bioavailability have arisen recently with the growing availibility of highly purified procoagulant proteins and increased interest in gene therapy of hemophilia B. Therefore, a group of studies were undertaken to determine the absorption rate, plasma recovery, and bioavailability of high purity, human plasma-derived F.IX concentrates administered via extravascular routes in hemophilia B dogs and in one human hemophilia B subject. Five hemophilia B dogs were given human F.IX via either a subcutaneous (SC), intramuscular (IM), intra- peritoneal (IP) or intravenous (IV) route. In a subsequent study, a single SC administration of human F.IX was compared to an identical IV dose of F.IX in the human hemophilia B subject. All extravascular routes of F.IX administration in both the canine and human gave lower levels of circulating plasma F.IX than the IV route, however all routes resulted in measurable F.IX activity. Of the extravascular routes, the IM injection in the canine resulted in a bioavailibility of 82.8%, while the SC injection resulted in a bioavailability of 63.5%. F.IX reached the plasma compartment by all extravascular routes used, confirming that F.IX can be absorbed extravascularly. The duration of measurable F.IX activity following extravascular administration is prolonged beyond that typically seen with IV administration. These data show that significant levels of F.IX may be obtained via SC injection in canine and ‘ human hemophilia B subjects and further highlight the potential of extravascular routes of administration for future experimental and clinical uses of F.IX and other procoagulant proteins.

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Current Therapy in Hematology/Oncology

Pathology ◽

10.3109/00313028609087580 ◽

1986 ◽

Vol 18 (4) ◽

pp. 487

Author(s):

Roger D. Scurr

Keyword(s):

Current Therapy

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Current Therapy of Diabetic Macular Edema Bevacizumab, Triamcinolone Acetonide, and Laser Photocoagulation

Ophthalmologica Indonesiana ◽

10.35749/journal.v45i1.172 ◽

2019 ◽

Vol 45 (1) ◽

pp. 13

Author(s):

Gladys Kusumowidagdo ◽

Randy Sarayar ◽

Kartika Rahayu ◽

Gitalisa Andayani

Keyword(s):

Macular Edema ◽

Triamcinolone Acetonide ◽

Diabetic Macular Edema ◽

Systematic Reviews ◽

Laser Photocoagulation ◽

Meta Analysis ◽

Intravitreal Bevacizumab ◽

Current Therapy ◽

Intravitreal Triamcinolone ◽

Mesh Terms

Background: Diabetic macular edema (DME) is the main cause of visual impairment in diabetic retinopathy (DR). Current gold standard therapy of DME is macular laser photocoagulation (MPC). Growing evidences have shown benefits of intravitreal anti-VEGF agents (i.e bevacizumab) and intravitreal corticosteroids (i.e triamcinolone acetonide). Aim: To compare the visual acuity (VA) improvement of patients with DME, treated with intravitreal bevacizumab (IVB), a combination of IVB and intravitreal triamcinolone (IVB/IVT), and MPC. Method: A comprehensive PubMed® and Cochrane® databases search was conducted on May 4th, 2017 using appropriate keywords (diabetic macular edema, bevacizumab, triamcinolone, and laser photocoagulation using their MeSH terms). Studies were filtered using inclusion criterions (clinical trials, RCT, meta-analysis, systematic review, English, humans, and publication within 10 years) Results: Three studies (2 systematic reviews and 1 RCT) were found suitable. From these results, all studies showed favoring effects of IVB when compared to IVB/IVT combination and MPC in short term period (up to 6 months). However, there was no significant improvement of VA beyond this period in all groups. Conclusion: IVB appears to be superior to IVB/IVT and MPC in improving VA during 6 months follow- up period. Future systematic reviews and meta-analysis are required on the effect of IVB and MPC combination in cases of DME.

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Novel Nano Carriers for the Treatment of Progressive Auto Immune Disease Rheumatoid Arthritis

Current Pharmaceutical Design ◽

10.2174/1381612826666201021130146 ◽

2020 ◽

Vol 26 ◽

Author(s):

Ritu Mishra ◽

Swati Gupta

Keyword(s):

Rheumatoid Arthritis ◽

Drug Delivery ◽

Autoimmune Disease ◽

Drug Delivery Systems ◽

Clinical Manifestations ◽

Adaptive Immune Response ◽

Delivery Systems ◽

Current Therapy ◽

Genetic And Environmental Factors ◽

Novel Drug

Background: Rheumatoid arthritis (RA) is the most common occurring progressive, autoimmune disease, affecting 1% of the population and the ratio of affected women is three times as compared to men in most developing countries. Clinical manifestations of RA are the presence of anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF) in blood, tendered joints and soreness of the muscles. Some other factors which may lead to chronic inflammation are genetic and environmental factors as well as adaptive immune response. Several conventional drugs are available for the treatment of RA but have their own drawbacks which can be overcome by the use of novel drug delivery systems. : The objective of the present review is to focus on the molecular pathogenesis of the disease and its current conventional treatment with special reference to the role of novel drug delivery systems encapsulating anti rheumatic drugs and herbal drugs in passive and receptor mediated active targeting against RA. On reviewing the conventional and current therapeutics agains RA, we conclude that, although the current therapy for the treatment of RA is capable enough, yet more advances in the field of targeted drug delivery will sanguinely result in effective and appropriate treatment of this autoimmune disease.

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Towards Breast Cancer Vaccines, Progress and Challenges

Current Drug Discovery Technologies ◽

10.2174/1570163815666180502164652 ◽

2019 ◽

Vol 16 (3) ◽

pp. 251-258 ◽

Cited By ~ 3

Author(s):

Javad Behravan ◽

Atefeh Razazan ◽

Ghazal Behravan

Keyword(s):

Breast Cancer ◽

Adverse Effects ◽

Cancer Vaccine ◽

Cancer Vaccines ◽

Weight Control ◽

The Body ◽

Phase Iii ◽

Current Therapy ◽

Surgical Ablation ◽

Breast Cancer Vaccine

Breast cancer is the second leading cause of cancer death among women. National cancer institute of the US estimates that one in eight women will be diagnosed with breast cancer during their lifetime. Considering the devastating effects of the disease and the alarming numbers many scientists and research groups have devoted their research to fight breast cancer. Several recommendations are to be considered as preventing measures which include living a healthy lifestyle, regular physical activity, weight control and smoking cessation. Early detection of the disease by annual and regular mammography after the age of 40 is recommended by many healthcare institutions. This would help the diagnosis of the disease at an earlier stage and the start of the treatment before it is spread to other parts of the body. Current therapy for breast cancer includes surgical ablation, radiotherapy and chemotherapy which is often associated with adverse effects and even may lead to a relapse of the disease at a later stage. In order to achieve a long-lasting anticancer response with minimal adverse effects, development of breast cancer vaccines is under investigation by many laboratories. The immune system can be stimulated by a vaccine against breast cancer. This approach has attracted a great enthusiasm in recent years. No breast cancer vaccines have been approved for clinical use today. One breast cancer vaccine (NeuVax) has now completed clinical trial phase III and a few preventive and therapeutic breast cancer vaccines are at different steps of development. We think that with the recent advancements in immunotherapy, a breast cancer vaccine is not far from reach.

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Novel Scaffolds for Leishmania infantum Trypanothione Reductase Inhibitors Derived from Brazilian Natural Products Biodiversity

Anti-Infective Agents ◽

10.2174/2211352518666200131121308 ◽

2021 ◽

Vol 18 (4) ◽

pp. 398-418

Author(s):

Vinícius Guimarães da Paixão ◽

Samuel Silva da Rocha Pita

Keyword(s):

Natural Products ◽

Leishmania Infantum ◽

In Vitro Assays ◽

Current Therapy ◽

Pharmacokinetic Analysis ◽

Trypanothione Reductase ◽

Resistant Species ◽

Reductase Inhibitors ◽

Thiol Redox

Background: Leishmania infantum causes the most lethal form of Leishmaniasis: Visceral leishmaniasis. Current therapy for this disease is related to the development of drug-resistant species and toxicity. Trypanothione Reductase (LiTR), a validated target for the drug discovery process, is involved with parasites' thiol-redox metabolism. Objective: In this study, through Virtual Screening employing two distinct Natural Products Brazilian databases, we aimed to identify novel inhibitor scaffolds against LiTR. Results: Thus, the “top 10” LiTR-ligand energies have been selected and their interaction profiles into LiTR sites through the AuPosSOM server have been verified. Finally, Pred-hERG, Aggregator Advisor, FAF-DRUGS, pkCSM and DataWarrior were employed and their results allowed us to evaluate, respectively, the cardiotoxicity, aggregation capacity, presence of false-positive compounds (PAINS) and their toxicities. Conclusion: Three molecules that overcame the in silico pharmacokinetic analysis and have a good interaction with LiTR, were chosen to use in vitro assays hoping that our computational results reported here would aid the development of new anti-leishmanial compounds.

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The Problem of Ventricular Dysrhythmias and Sudden Death Mortality in Heart Failure: The Impact of Current Therapy

Cardiology ◽

10.1159/000007003 ◽

2000 ◽

Vol 93 (1-2) ◽

pp. 56-69 ◽

Cited By ~ 5

Author(s):

Carl V. Leier ◽

Rene J. Alvarez ◽

Philip F. Binkley

Keyword(s):

Heart Failure ◽

Sudden Death ◽

Current Therapy ◽

Ventricular Dysrhythmias ◽

The Impact

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Considerations for Home-Based Treatment of Fabry Disease in Poland during the COVID-19 Pandemic and Beyond

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18168242 ◽

2021 ◽

Vol 18 (16) ◽

pp. 8242

Author(s):

Michał Nowicki ◽

Stanisława Bazan-Socha ◽

Mariusz Kłopotowski ◽

Beata Błażejewska-Hyżorek ◽

Mariusz Kusztal ◽

...

Keyword(s):

Fabry Disease ◽

Genetic Diseases ◽

Healthcare Providers ◽

Treatment Programs ◽

Current Therapy ◽

Term Care ◽

Pharmacological Chaperone ◽

Enzyme Replacement ◽

Home Based ◽

Rare Genetic Diseases

Current therapy for Anderson–Fabry disease in Poland includes hospital or clinic-based intravenous enzyme replacement therapy with recombinant agalsidase alpha or beta, or oral pharmacological chaperone therapy with migalastat. Some countries around the world offer such treatment to patients in the comfort of their own homes. The 2020–2021 COVID-19 pandemic has pushed global healthcare providers to evolve their services so as to minimize the risk of COVID-19 exposure to both patients and providers; this has led to advances in telemedicine services and the increasing availability of at-home treatment for various procedures including parenteral drug administration. A total of 80% of surveyed Anderson–Fabry disease patients in Poland would prefer home-based treatment, which would be a safe and convenient alternative to clinic-based treatment if patient selection is based on our proposed algorithm. Our recommendations for home-based treatments appear feasible for the long term care of Anderson–Fabry disease patients during the COVID-19 pandemic and beyond. This may also serve as a basis for home-based treatment programs in other rare and ultra-rare genetic diseases.

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MBRS-48. IDENTIFICATION OF NOVEL THERAPEUTIC APPROACHES FOR MYC-DRIVEN MEDULLOBLASTOMA

Neuro-Oncology ◽

10.1093/neuonc/noaa222.557 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii406-iii406

Author(s):

Kübra Taban ◽

David Pauck ◽

Mara Maue ◽

Viktoria Marquardt ◽

Hua Yu ◽

...

Keyword(s):

New Drugs ◽

Current Therapy ◽

Cancer Drug ◽

Mrna Levels ◽

Cell Models ◽

Therapeutic Approaches ◽

Group 3 ◽

Novel Therapeutic

Abstract Medulloblastoma (MB) is the most common malignant brain tumor in children and is frequently metastatic at diagnosis. Treatment with surgery, radiation and multi-agent chemotherapy may leave survivors of these brain tumors with long-term deficits as a consequence. One of the four consensus molecular subgroups of MB is the MYC-driven group 3 MB, which is the most malignant type and has a poor prognosis under current therapy. Thus, it is important to discover more effective targeted therapeutic approaches. We conducted a high-throughput drug screening to identify novel compounds showing efficiency in group 3 MB using both clinically established inhibitors (n=196) and clinically-applicable compounds (n=464). More than 20 compounds demonstrated a significantly higher anti-tumoral effect in MYChigh (n=7) compared to MYClow (n=4) MB cell models. Among these compounds, Navitoclax and Clofarabine showed the strongest effect in inducing cell cycle arrest and apoptosis in MYChigh MB models. Furthermore, we show that Navitoclax, an orally bioavailable and blood-brain barrier passing anti-cancer drug, inhibits specifically Bcl-xL proteins. In line, we found a significant correlation between BCL-xL and MYC mRNA levels in 763 primary MB patient samples (Data source: “R2 https://hgserver1.amc.nl”). In addition, Navitoclax and Clofarabine have been tested in cells obtained from MB patient-derived-xenografts, which confirmed their specific efficacy in MYChigh versus MYClow MB. In summary, our approach has identified promising new drugs that significantly reduce cell viability in MYChigh compared to MYClow MB cell models. Our findings point to novel therapeutic vulnerabilities for MB that need to be further validated in vitro and in vivo.

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