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Sample records for anti psoriasis therapies

  1. Elevation of serum KL-6 in patients with psoriasis treated with anti-tumour necrosis factor-α therapy.

    PubMed

    Higashi, Y; Tada, K; Shimokawa, M; Kawai, K; Kanekura, T

    2016-01-01

    We report three patients with psoriasis whose serum level of Krebs Von Den Lungen (KL)-6 increased during therapy with anti-tumour necrosis factor (TNF)-α. A diagnosis of early-phase or subclinical interstitial pneumonia was made in two patients, and their KL-6 level decreased after anti-TNF-α discontinuation. The rise in KL-6 in the other patient was attributed to methotrexate. We propose that serum KL-6 should be monitored routinely in patients treated with anti-TNF agents. PMID:25557847

  2. Psoriasis treatment: traditional therapy

    PubMed Central

    Lebwohl, M; Ting, P; Koo, J

    2005-01-01

    Even before the recent development of biological agents, a long list of effective treatments has been available for patients with psoriasis. Topical therapies such as corticosteroids, vitamin D analogues, and retinoids are used for localised disease. Phototherapy including broadband ultraviolet B (UVB), narrowband UVB, PUVA, and climatotherapy are effective for more extensive disease. Systemic therapies such as methotrexate, retinoids, and ciclosporin are effective for patients with refractory or extensive cutaneous disease. PMID:15708945

  3. Conventional therapies for psoriasis.

    PubMed

    Rebora, A

    2007-01-01

    Conventional treatments of psoriasis include topical and systemic drugs. For sake of brevity, the presentation will deal only with systemic therapy. Three drugs are presently available in Italy: methotrexate, acitretin and cyclosporin A. Their efficacy is almost identical, all of them achieving PASI 75 in about 60% of cases in 12 weeks The indications (which, in Italy, do not include psoriasis for methotrexate), the contraindications, the interactions, the adverse effects and the precautions in their use will be discussed. Methotrexate side effects account for more than 10% of cases and include nausea and vomiting and chiefly increase of blood levels of liver enzymes. Acitretin side effects are numerous and varied, the most severe being increase of liver enzymes and blood lipids, renal impairment, and teratogenicity. Cyclosporin side effects are chiefly hypertension and renal failure. The Author concludes that cyclosporin is the drug with the best efficacy/side effect ratio, though it should be used in selected cases. PMID:17828351

  4. [Classical topical therapy of psoriasis].

    PubMed

    Gerdes, S; Mrowietz, U

    2006-08-01

    In most cases mild to moderate forms of psoriasis can be treated with topical therapy. In addition, topical agents are also routinely combined with UV or systemic therapy to treat severe forms of psoriasis. A variety of standard products are available. The oldest topical treatment is anthralin. Since 1952 the development of topical corticosteroids has revolutionized not only dermatological treatment in general but the treatment of psoriasis in particular. Through the continuous development of these compounds, a better risk-benefit profile has been achieved. Corticosteroids are the most frequently employed topical agent for psoriasis treatment worldwide. PMID:16841204

  5. Asymmetric dimethylarginine but not osteoprotegerin correlates with disease severity in patients with moderate-to-severe psoriasis undergoing anti-tumor necrosis factor-α therapy.

    PubMed

    Pina, Trinitario; Genre, Fernanda; Lopez-Mejias, Raquel; Armesto, Susana; Ubilla, Begoña; Mijares, Veronica; Dierssen-Sotos, Trinidad; Corrales, Alfonso; Gonzalez-Lopez, Marcos A; Gonzalez-Vela, Maria C; Blanco, Ricardo; Hernández, Jose L; Llorca, Javier; Gonzalez-Gay, Miguel A

    2016-04-01

    Patients with psoriasis, in particular those with severe disease, have an increased risk of cardiovascular (CV) events compared with the general population. The aim of the present study is to determine whether correlation between asymmetric dimethylarginine (ADMA) and osteoprotegerin (OPG), two biomarkers associated with CV disease, and disease severity may exist in patients with moderate-to-severe psoriasis. We also aimed to establish if baseline serum levels of these two biomarkers could correlate with the degree of change in the clinical parameters of disease severity following the use of anti-tumor necrosis factor (TNF)-α therapy in these patients. This was a prospective study on a series of consecutive non-diabetic patients with moderate-to-severe psoriasis who completed 6 months of therapy with anti-TNF-α-adalimumab. Patients with kidney disease, hypertension or body mass index of 35 kg/m(2) or more were excluded. Metabolic and clinical evaluation was performed immediately prior to the onset of treatment and at month 6. Twenty-nine patients were assessed. Unlike OPG, a significant positive correlation between ADMA and resistin serum levels was found at the onset of adalimumab and also after 6 months of biologic therapy. We also observed a positive correlation between the percent of body surface area affected (BSA) and ADMA levels obtained before the onset of adalimumab and a negative correlation between baseline ADMA levels and a 6-month BSA change compared with baseline results. In patients with moderate-to-severe psoriasis, ADMA levels correlate with clinical markers of disease severity. PMID:26364678

  6. Psoriasis

    MedlinePlus

    ... eg, ibuprofen, naproxen), lithium, antimalarial drugs, and oral steroid withdrawal. Approximately 10–30% of people with psoriasis ... The mainstay of therapy for psoriasis is topical steroids, either in creams or ointment form. Higher-potency ...

  7. Psoriasis

    MedlinePlus

    ... treatment of psoriasis with biologics. J Am Acad Dermatol . 2008;5:826-850. PMID: 18423260 www.ncbi. ... of psoriasis with topical therapies. J Am Acad Dermatol . 2009;60:643-659. PMID: 19217694 www.ncbi. ...

  8. Treating Psoriasis: Complementary and Alternative Therapies

    MedlinePlus

    ... or safe. Read more about herbal remedies » Mind/Body Therapies Mind-body techniques can help reduce your stress levels. Learn about mind/body therapies » Alternative Therapies Some psoriasis patients report hands- ...

  9. [Vipsogal in the therapy of psoriasis].

    PubMed

    Skripkin, Iu K; Shakhtmeĭster, I Ia; Kubanov, A A; Kaukhova, O Ia

    1990-01-01

    A new external drug, vipsogal, manufactured by Galenika, Yugoslavia, was used in therapy of 205 patients suffering from psoriasis. The drug proved to be fairly effective. The authors recommend vipsogal to be included in the complex of drugs used in therapy of psoriasis. PMID:2094099

  10. Psoriasis

    MedlinePlus

    ... worse include Infections Stress Dry skin Certain medicines Psoriasis usually occurs in adults. It sometimes runs in families. Treatments include creams, medicines, and light therapy. NIH: National ...

  11. New systemic therapies for psoriasis.

    PubMed

    Mansouri, Yasaman; Goldenberg, Gary

    2015-03-01

    Over the last decade, expanded understanding of psoriasis pathogenesis has led to the development of new systemic agents such as biological drugs that have revolutionized the treatment of psoriasis. Small molecule inhibitors also have been studied and offer patients options for oral administration. This article reviews recently approved and in-the-pipeline biologics (IL-17 inhibitors and IL-23 blockers) as well as small molecule inhibitors (phosphodiesterase 4 [PDE4] and Janus kinase [Jak] inhibitors). PMID:25844781

  12. [Pruritus in psoriasis : Profile and therapy].

    PubMed

    Tsianakas, A; Mrowietz, U

    2016-08-01

    Psoriasis is a common chronic inflammatory disease with an incidence of about 0.5-3 %. Previously psoriasis was not primarily regarded to be associated with pruritus; however, this perception has changed in recent years. Meanwhile data conclusively show that between 64 and 97 % of patients report about pruritus that can be severe in a number of cases. Apart from suffering from psoriasis, the presence of pruritus causes additional stress and leads to a significant impairment of health-related quality of life. Neurogenic inflammation at least in part contributes to the development of pruritus in psoriasis skin lesions. A number of neuropeptides including substance P and calcitonin gene related peptide can act as pro-inflammatory mediators. There is evidence for a dysbalance between κ‑ and µ‑opioid receptors in lesional skin favoring inflammation and pruritus. After clearing of psoriasis lesions, pruritus is relieved as well. Therefore, specific treatment of pruritus is not necessary in general. In cases where severe pruritus is a prominent symptom, targeted therapy with mirtazapin or doxepin or neuroleptic compounds such as pregabalin or gabapentin or drugs affecting the κ‑ und µ‑opioid receptor balance can be administered. Today the importance of pruritus as a prominent symptom of psoriasis lesions has been widely accepted. In recent and running clinical trials with new drugs, pruritus at baseline and the effect of these drugs on pruritus is always assessed. This awareness also fuels basic research about pruritus in psoriasis. PMID:27376751

  13. Psoriasis

    PubMed Central

    Di Meglio, Paola; Villanova, Federica; Nestle, Frank O.

    2014-01-01

    Psoriasis is a common chronic inflammatory skin disease with a spectrum of clinical phenotypes and results from the interplay of genetic, environmental, and immunological factors. Four decades of clinical and basic research on psoriasis have elucidated many of the pathogenic mechanisms underlying disease and paved the way to effective targeted therapies. Here, we review this progress and identify future directions of study that are supported by a more integrative research approach and aim at further improving the patients' life. PMID:25085957

  14. Severe Psoriasis Flare After Anti-Programmed Death Ligand 1 (PD-L1) Therapy for Metastatic Non-Small Cell Lung Cancer (NSCLC).

    PubMed

    Chia, Puey Ling; John, Thomas

    2016-06-01

    Immunomodulatory agents that target PD-1 and its ligand (PD-L1) are being increasingly used in the management of lung cancer. Potential immune-related adverse events include dermatological complications which mostly are of low grade severity. The use of immune checkpoint inhibitors may lead to the exacerbation of autoimmune conditions. We report a case of a documented psoriasis flare with anti-PD-1 treatment for lung cancer. PMID:27163740

  15. Progress in Psoriasis Therapy via Novel Drug Delivery Systems

    PubMed Central

    Vincent, Nitha; Ramya, Devi D; Vedha, Hari BN

    2014-01-01

    Psoriasis is a lifelong condition which is caused by the negative signals produced by immune system, which leads to hyper proliferation and other inflammatory reactions on the skin. In this case, keratinocytes which are the outermost layer of skin possess shortened life cycle and results in the alteration of desquamation process where the cytokines will come out through lesions of affected patients and as a result, scaling marks appears on the skin. These conditions may negatively affect the patient’s quality of life and lead to psychosocial stress. Psoriasis can be categorized as mild, moderate and severe conditions. Mild psoriasis leads to the formation of rashes, and when it becomes moderate, the skin turns into scaly. In severe conditions, red patches may be present on skin surface and becomes itchy. Topical therapy continues to be one of the pillars for psoriasis management. Drug molecules with target effect on the skin tissues and other inflammations should be selected for the treatment of psoriasis. Most of the existing drugs lead to systemic intoxication and dryness when applied in higher dose. Different scientific approaches for topical delivery are being explored by researches including emollient, modified gelling system, transdermal delivery, spray, nanogels, hydrogels, micro/nano emulsion, liposomes, nano capsules etc. These topical dosage forms are evaluated for various physico chemical properties such as drug content, viscosity, pH, extrudability, spreadability, toxicity, irritancy, permeability and drug release mechanism. This review paper focus attention to the impact of these formulation approaches on various anti-psoriasis drugs for their successful treatment. PMID:25386329

  16. Psoriasis

    MedlinePlus

    ... version of this page please turn Javascript on. Psoriasis What Is Psoriasis? Psoriasis (sow RYE uh sis) is a chronic ... more information Click for more information Types of Psoriasis Psoriasis occurs in five different forms that affect ...

  17. Psoriasis

    MedlinePlus

    ... Here's Help White House Lunch Recipes Skin Problem: Psoriasis KidsHealth > For Kids > Skin Problem: Psoriasis Print A ... Do? en español Problemas en la piel: psoriasis Psoriasis = Red, Flaky Skin If you have psoriasis, you ...

  18. Nanostructures of an amphiphilic zinc phthalocyanine polymer conjugate for photodynamic therapy of psoriasis.

    PubMed

    Jin, Yiguang; Zhang, Xiaohan; Zhang, Baolei; Kang, Hongxiang; Du, Lina; Li, Miao

    2015-04-01

    Psoriasis is a chronic inflammatory skin disease affecting 2-5% of the population worldwide and it severely affects patient quality of life. In this study, an amphiphilic zinc phthalocyanine polymer conjugate (ZPB) was synthesized, in which zinc phthalocyanine (ZnPc) was conjugated with the poly(ethylene glycol) (PEG) chain of Brij 58. ZPB showed two maximum UV-vis absorption wavelengths, 348 nm and 678 nm. A monomolecular micelle of ZPB formed in water with a mean size of 25 nm and zeta potential of -15 mV. The nanostructures aggregated into cloudy precipitates, which were easily dispersed. The nanostructure showed the shell-core structure with the ZnPc segments as the core and the PEG chains as the shell. The anti-psoriasis effect of the ZPB nanostructure was explored using a guinea pig psoriasis model. After comparing the anti-psoriasis effects of saline, light alone, ZPB alone, and the combination of light and ZPB, the combination of light and ZPB showed the best photodynamic therapy of psoriasis based on the light excitation of the photosensitizer ZPB and the psoriasis was nearly cured according to the histopathological investigation. The ZPB nanostructure is a promising anti-psoriasis nanomedicine based on photodynamic therapy. PMID:25766924

  19. Anti-interleukin-17 treatment of psoriasis.

    PubMed

    Jinna, Sphoorthi; Strober, Bruce

    2016-08-01

    Psoriasis is a chronic, immune-mediated, inflammatory dermatosis, affecting 2-3% of the US population. While first-generation cytokine antagonists targeting tumor necrosis factor alpha (TNF-α)-dependent pathways have produced favorable responses in the treatment of psoriasis, higher levels of efficacy in a greater proportion of patients have been shown in trials with antibodies targeting interleukin (IL)-17A and the IL-17 receptor subunit. This examines the role of IL-17 inhibitors in the treatment of plaque psoriasis. The efficacy and safety results from the phase-3 trials with monoclonal antibodies targeting IL-17RA (brodalumab) and IL-17A (ixekizumab and secukinumab) validate IL-17 as a highly effective therapeutic target for the treatment of plaque psoriasis. PMID:26943806

  20. Fixed-dose combination therapy for psoriasis.

    PubMed

    Guenther, Lyn C

    2004-01-01

    Fixed-dose combination therapy offers stable products containing two or more medications with different mechanisms of action and safety profiles. It is also convenient for patients since only one product rather than two or more needs to be applied. Topical corticosteroids are often the mainstay of therapy in psoriasis. Diprosalic and Nerisalic contain a topical corticosteroid (betamethasone dipropionate and diflucortolone, respectively) and salicylic acid. A left/right study showed that both products have comparable efficacy. It has also been shown that betamethasone dipropionate + salicylic acid ointment has similar efficacy to clobetasol and calcipotriene (calcipotriol) ointments. Betamethasone dipropionate + salicylic acid lotion has similar efficacy to clobetasol lotion. Faster improvement of scaling, itching, and redness was noted with betamethasone dipropionate + salicylic acid lotion compared with betamethasone dipropionate alone. Dovobet (Daivobet) ointment is a fixed-dose combination product containing betamethasone dipropionate and calcipotriene. Clinical studies have shown that it has greater efficacy and a faster speed of onset than the individual components or tacalcitol. Once daily and twice daily treatments have similar efficacy. Psoriasis Area and Severity Index reductions of approximately 40% after 1 week and 70% after 4 weeks of therapy were consistently noted in six large international studies involving >6000 patients. Betamethasone dipropionate + calcipotriene treatment is associated with approximately 75% less adverse cutaneous events as compared with tacalcitol, 50% less compared with calcipotriene, and a similar number as treatment with betamethasone dipropionate. PMID:15109271

  1. [Topical corticosteroids and corticosteroid sparing therapy in psoriasis management].

    PubMed

    Sukarovska, Biljana Gorgievska; Lipozencić, Jasna; Vrzogić, Pero

    2007-09-01

    Psoriasis is a chronic, recurrent, genetically determined, inflammatory dermatosis that affects the skin, scalp and joints. Psoriasis is caused by various triggers (infections, drugs, physical and emotional factors). It ranges in severity from mild to severe, and patients with moderate to severe disease suffer significant deterioration in the quality of life. Clinical types of psoriasis are psoriasis guttata, nummular psoriasis, plaque, generalized and erythrodermic psoriasis. Skin changes affect intertriginous regions (inverse psoriasis), and there also are special forms of pustular psoriasis and arthropathic psoriasis. The goals of psoriasis treatment are to gain initial and rapid control of the disease; to decrease plaque lesions and percentage of body surface area involved, to achieve long-term remission; and to minimize adverse events. Topical treatment for mild psoriasis includes topical corticosteroids, calcipotriene, tazarotene, topical tars, anthralin and keratolytics, and immunomodulators (pimecrolimus, tacrolimus). The treatment of moderate to severe psoriasis includes systemic therapies such as methotrexate, acitretin, cyclosporine, hydroxurea and biologicals. Topical treatment can be effective using combination, rotational or sequential regimens for patients with more severe disease. The aim of successful treatment of psoriasis is fast control of the disease and regression of lesions in a short period, prolonged remission and minimal adverse reaction. Local therapy with various topicals is administered for mild and localized forms of the disease, with or without phototherapy (UVB). Topical corticosteroids are used in a variety of formulations, with a potential ranging from superpotent to least potent (class 1-7), which decrease symptoms in tne first two weeks of treatment with improvement in subsequent weeks; D3 vitamin analog (effective in 6-8 weeks), retinoids (effective in 1-2 weeks), tars (2-4 weeks), anthralin (2-4 weeks), and keratolytics (most

  2. Identification of key research needs for topical therapy treatment of psoriasis - a consensus paper by the International Psoriasis Council.

    PubMed

    Wu, J J; Lynde, C W; Kleyn, C E; Iversen, L; van der Walt, J M; Carvalho, A; Kirby, B; Bissonnette, R

    2016-07-01

    In this age of expanding choices of therapy for psoriasis, topical therapies still play an important part in the management of patients. There are many knowledge gaps in topical therapy for psoriasis with regard to efficacy and safety as well as various combinations including topical therapy with phototherapy or with systemic agents. Councillors of the International Psoriasis Council comprised a topical therapy working group to describe these gaps in order to help direct future research endeavours. Herein, we present the results of this analysis, discuss topical agents in clinical development and the attributes of the ideal topical treatment for psoriasis. PMID:26969587

  3. Tailor systemic therapy to the patient with severe psoriasis.

    PubMed

    Van de Velde, Vanessa; Tidman, Michael J

    2016-02-01

    There is no standard definition regarding the severity of psoriasis, and a number of factors should be considered, including the extent and stability of skin disease, involvement of joints, response to treatment, and impact on quality of life. Erythrodermic psoriasis and pustular psoriasis are severe conditions and the patient may be systemically unwell and febrile. NICE recommends that four key areas should be evaluated and recorded when assessing patients: severity, using the static Physician's Global Assessment (sPGA); disease impact on physical, psychological and social wellbeing using the Dermatology Life Quality Index (DLQI); the presence of psoriatic arthritis; and comorbidities. Ideally, patients should be assessed annually for psoriatic arthritis: the Psoriasis Epidemiology Screening Tool is a validated tool to screen for psoriatic arthritis in primary and secondary care. Patients with severe psoriasis should undergo cardiovascular risk assessment at presentation and every five years, or more frequently if indicated. Referral to secondary care should be made for patients with any type of psoriasis with poor response to topical therapy (after 2 or 3 months according to SIGN) and for extensive psoriasis. Cases where the psoriasis is having a significant physical or psychological impact on an individual's quality of life warrant early referral, as do those where the diagnosis is uncertain. Patients with generalised pustular psoriasis or erythroderma should be referred urgently for same-day specialist input. Patients with acute guttate psoriasis who may require phototherapy should also be referred. Children and adolescents with any type of psoriasis should be referred to a specialist at initial presentation. PMID:27032223

  4. Psoriasis

    MedlinePlus

    ... in Residency Young Physician Focus Dermatology Daily AAD Buyer's Guide Awards, grants, and scholarships AAD Annual Meeting ... take control. Learn about psoriasis . Knowledge really is power. Learning about psoriasis will help you manage the ...

  5. Psoriasis

    MedlinePlus

    ... parts of your body. Some people who have psoriasis also get a form of arthritis called psoriatic arthritis. A problem with your immune system causes psoriasis. In a process called cell turnover, skin cells ...

  6. [Immunopathogenesis of psoriasis and its current therapy ].

    PubMed

    Svozil, M

    2002-09-01

    Psoriasis is a partly inflammatory hyperproliferative skin disease. Its origin has not been clarified yet, but numerous immunologic, bioregulatory, and biochemical changes accompanying this disease are known. Many cell types and a number of immunity system factors forming a perfectly interlinked network are involved in the immunity processes in the psoriasis-affected skin. This network is a common place where antipsoriatics operate. There is no therapeutic means known which guarantees permanent elimination of psoriasis symptoms. External as well as internal therapeutic methods having effect on the pathogenetic processes at various levels are combined. UV radiation treatment (SUP), sometimes combined with psoralens (PUVA), tar, and dithranol are some of the classical methods of psoriasis treatment. Topical medicamentous treatment with corticoids, vitamin D derivatives, salicylic acid, urea, and tar plays an important part here. PMID:12407918

  7. A Review of Psoriasis, Therapies, and Suicide.

    PubMed

    Gooderham, Melinda; Gavino-Velasco, Jennifer; Clifford, Cole; MacPherson, Alex; Krasnoshtein, Flora; Papp, Kim

    2016-07-01

    Many chronic medical disorders are associated with psychiatric morbidity. Yet the psychological burden of these disorders often goes unnoticed. In dermatology, psoriasis has a higher association with psychiatric illness, including depression and suicide risk, compared with many other conditions. Studies suggest that effective treatment of psoriasis results in the improvement of psychiatric morbidity, particularly depression and anxiety. New biologic treatments for psoriasis may offer help beyond clearing of the skin in these patients and may lead to a reduction of psychiatric morbidity. Although concerns have been raised regarding the potential link between interleukin-17R blockade in the treatment of psoriasis and suicide, current literature provides no evidence to support this association. PMID:27207348

  8. Tumorigenicity of a combination of psoriasis therapies.

    PubMed Central

    Phillips, D. H.; Alldrick, A. J.

    1994-01-01

    Coal tar, a tumour initiator, and dithranol, a tumour promoter, are used in the treatment of psoriasis. Topical treatment of mice with pharmaceutical formulations of these two agents, at therapeutic doses, induced skin papillomas in a classical two-stage carcinogenesis protocol, while treatment with either agent alone did not. This finding has implications for the use of both agents in combination in the treatment of psoriasis. Images Figure 1 PMID:8198968

  9. Psoriasis.

    PubMed

    Boehncke, Wolf-Henning; Schön, Michael P

    2015-09-01

    Psoriasis is an immune-mediated, genetic disease manifesting in the skin or joints or both. A diverse team of clinicians with a range of expertise is often needed to treat the disease. Psoriasis provides many challenges including high prevalence, chronicity, disfiguration, disability, and associated comorbidity. Understanding the role of immune function in psoriasis and the interplay between the innate and adaptive immune system has helped to manage this complex disease, which affects patients far beyond the skin. In this Seminar, we highlight the clinical diversity of psoriasis and associated comorbid diseases. We describe recent developments in psoriasis epidemiology, pathogenesis, and genetics to better understand present trends in psoriasis management. Our key objective is to raise awareness of the complexity of this multifaceted disease, the potential of state-of-the-art therapeutic approaches, and the need for early diagnosis and comprehensive management of patients with psoriasis. PMID:26025581

  10. Current and future oral systemic therapies for psoriasis.

    PubMed

    Kelly, John B; Foley, Peter; Strober, Bruce E

    2015-01-01

    For patients with moderate to severe psoriasis, there is a large range of variably effective and safe oral, systemic medications. With appropriate monitoring, these therapies may be used as either monotherapy or in combination with other therapies. Newer drugs in the research pipeline hold significant promise. PMID:25412786

  11. Optimizing topical therapies for treating psoriasis: a consensus conference.

    PubMed

    Zeichner, Joshua A; Lebwohl, Mark G; Menter, Alan; Bagel, Jerry; Del Rosso, James Q; Elewski, Boni E; Feldman, Steven R; Kircik, Leon H; Koo, John; Gold, Linda Stein; Tanghetti, Emil

    2010-09-01

    In 2010, an expert committee of physicians and researchers in the field of dermatology working together as the Psoriasis Process of Care Consensus Panel developed consensus guidelines for the treatment of psoriasis. As much as possible, the guidelines were evidence based but also included the extensive clinical experience of the dermatologists. Psoriasis is a lifelong disease that requires long-term treatment and 80% of psoriasis patients have mild to moderate disease. Topical therapies play an important role in the treatment of psoriasis, especially in patients with mild to moderate disease. Patients usually start with monotherapy; however, in more severe cases (> 10% body surface area [BSA], severely impaired quality of life [QOL], or recalcitrant psoriatic lesions), multiple treatment modalities may be used as part of combination, sequential, or rotational therapeutic regimens. Main treatment options include topical steroids, systemic therapies, topical vitamin D treatments such as vitamin D3 ointment, retinoids, phototherapy, and biologic therapies. Other topical therapies include the following steroid-sparing agents: coal tar, anthralin, calcineurin inhibitors, keratolytics, and emollients. Therapeutic considerations also should focus on adherence, improving QOL, and promoting a good patient-physician relationship. PMID:21049712

  12. Targeted UV therapy in the treatment of psoriasis.

    PubMed

    Stein, Kevin R; Pearce, Daniel J; Feldman, Steven R

    2008-01-01

    Ultraviolet (UV) light is an effective treatment for extensive psoriasis and some other inflammatory skin conditions. Because the predominant effect of UV is a local one (as opposed to a systemic effect on immunity), localized delivery of ultraviolet B radiation (UVB) may be a useful treatment for localized variants of psoriasis and other conditions. The article reviews the literature regarding use of localized UV therapy. A theoretical benefit of localized UV therapy is reduced toxicity compared with whole-body therapy. Practical benefits in psoriasis treatment include higher efficacy and more appealing cosmesis compared with topicals. The 308-nm excimer laser is effective for psoriasis with fewer UVB treatments and lower total UVB exposure than needed for total body UV treatment. Other methods of localized UV delivery include quartz lamps, hand-held home UV devices, and non-laser intense photo sources. Other conditions treated with localized UV include vitiligo and lichen planus. Localized UV therapy is a useful modality for the treatment of localized variants of psoriasis with growing use for other dermatologic diseases. PMID:17934935

  13. Therapeutic moisturizers as adjuvant therapy for psoriasis patients.

    PubMed

    Gelmetti, Carlo

    2009-01-01

    At any point in time, psoriasis affects 2-3% of the world's population and has one of the biggest impacts on quality of life of any dermatological disorder. Treatment is extremely costly and prevention of disease progression in severity and extent is crucial. Psoriasis treatment should include skin hydration (regular use of moisturizers and emollients), careful, gentle skin cleansing, and identification and avoidance of Koebner phenomenon triggers (excoriation, maceration) and infectious foci (Streptococcus pyogenes). Moisturizers have been shown to significantly improve skin conditions and quality of life for psoriasis patients. They are a valuable first-line treatment, as dry skin is common and adds to the irritability of the diseased skin. Most patients respond well to topical treatment with topical corticosteroids, emollients, coal tar, anthralin (dithranol) or calcipotriol. Emollients are the most prescribed products, providing transient relief from irritation and some possessing anti-inflammatory properties. Moisturizers and emollients should be used in the following cases: minimal psoriasis, napkin psoriasis, psoriasis of the folds, psoriatic skin damaged by previous local treatments, and in pregnancy or women of childbearing age. PMID:19209948

  14. Novel psoriasis therapies and patient outcomes, part 1: topical medications.

    PubMed

    Feely, Meghan A; Smith, Barry L; Weinberg, Jeffrey M

    2015-03-01

    In recent years, advances in our understanding of inflammatory mediators and the underlying pathogenesis of psoriasis and psoriatic arthritis have shed light on potential therapeutic targets, which has led to the development of several new promising treatments. In this article, key clinical trials, mechanisms of action, patient outcomes, and relevant safety information for these novel topical medications will be evaluated. This article is the first in a 3-part series on treatments presently in the pipeline for the management of psoriasis and psoriatic arthritis including topical agents, biologic treatments, and systemic therapies in phase 2 and phase 3 clinical trials. With novel approaches to the disease process, these therapies may afford more targeted individualized treatment regimens and offer hope to patients with psoriasis and psoriatic arthritis who have reported a suboptimal therapeutic response to conventional therapies. PMID:25844785

  15. [Children and adolescents with psoriasis. What therapy is recommended?].

    PubMed

    Sticherling, M

    2012-03-01

    Juvenile psoriasis shows a cumulative incidence of 1.76% until the 18th year of life and thus is important for both pediatricians and dermatologists. In contrast to psoriasis in adults, the main trigger factors are infections, mechanical trauma and stress factors and to a much lesser extent medical and recreational drugs. Apart from the classical predilection sites, the diaper area, scalp and face are mainly involved. Guttate psoriasis following streptococcal infections is a specific clinical manifestation in childhood and adolescence. Psoriasis arthritis of childhood falls into the group of juvenile idiopathic arthritis and typically presents before or simultaneously with skin symptoms. All recommended childhood vaccinations should be administered, ideally when the disease is under remission. Therapy relies heavily on topical agents like dithranol, corticosteroids, and alternatively topical calcineurin inhibitors in addition to individually adapted skin moisturizing measures. In severe cases which do not adequately respond to topical therapy, systemic treatment with classical immunomodulatory agents like methotrexate, cyclosporin, retinoids and fumarates may be initiated but all usage is off-label. The only agent licensed for the treatment of psoriasis in patients above the age of 8 years is etanercept if classical treatment has failed. Rehabilitative measures in mountain and seaside areas are reasonable for maintaining improvement and helping patient learn to deal with disease. PMID:22382304

  16. Anti-TNF-α monoclonal antibody reverses psoriasis through dual inhibition of inflammation and angiogenesis.

    PubMed

    Liu, Yu; Yang, Guoyou; Zhang, Junfeng; Xing, Kaiyan; Dai, Lei; Cheng, Lin; Liu, Junli; Deng, Jie; Shi, Gang; Li, Chunlei; Su, Xiaolan; Zhang, Shuang; Yang, Yang; Li, Jia; Yu, Dechao; Xiang, Rong; Wei, Yuquan; Deng, Hongxin

    2015-09-01

    Tumor necrosis factor-alpha (TNF-α) antagonists have shown remarkable efficacy in psoriasis; however, the precise mechanisms of action of TNF-α blocking agents mainly focus on their neutralizing TNF-α and its anti-inflammatory effects. In this study, we generated a humanized anti-TNF-α monoclonal antibody (IBI303) and suggested a potential mechanism of anti-TNF-α therapy for psoriasis. The results of SPR and ELISA indicated that IBI303 has a good affinity to TNF-α. In vitro, it could suppress TNF-α-induced cytotoxicity in WEHI164 cells. In vivo, administration of IBI303 to K14-VEGF transgenic mice led to a significant treatment efficiency in psoriasis in a dose-dependent manner. IHC staining and cytokines-ELISA indicated that TNF-α inhibition strongly reduced inflammatory cells infiltration and pro-inflammatory cytokines release, accompanied by suppression of inflamed dermal blood vessels. Mechanistically, in order to explain the anti-angiogenesis effect of anti-TNF-α antibody, the production of cytokine in macrophage conditional medium was measured by ELISA. The result indicated that the massive secretion of TNF-α stimulated by LPS in RAW264.7 cell supernatant was markedly neutralized in a dose-response manner by IBI303, moreover, the expression of NF-κB p65 was down-regulated. Mouse endothelial cell tube formation assay showed that anti-TNF-α could inhibit blood vessels formation directly and indirectly. Collectively, our study suggested a kind of antipsoriatic mechanism of TNF-α inhibitors that is the dual inhibition of inflammation and angiogenesis. PMID:26263167

  17. Psoriasis

    MedlinePlus

    ... medications, infections, stress, or exposure to certain chemicals. Inverse psoriasis. Smooth, red patches occur in the folds ... questions about statistics, please contact Centers for Disease Control and Prevention, National Center for Health Statistics Website: ...

  18. Circulating levels of sphingosine-1-phosphate are elevated in severe, but not mild psoriasis and are unresponsive to anti-TNF-α treatment

    PubMed Central

    Checa, Antonio; Xu, Ning; Sar, Daniel G.; Haeggström, Jesper Z.; Ståhle, Mona; Wheelock, Craig E.

    2015-01-01

    Sphingolipids are bioactive molecules with a putative role in inflammation. Alterations in sphingolipids, in particular ceramides, have been consistently observed in psoriatic skin. Herein, we quantified the circulating sphingolipid profile in individuals with mild or severe psoriasis as well as healthy controls. In addition, the effects of anti-TNF-α treatment were determined. Levels of sphingoid bases, including sphingosine-1-phosphate (S1P), increased in severe (P < 0.001; n = 32), but not in mild (n = 32), psoriasis relative to healthy controls (n = 32). These alterations were not reversed in severe patients (n = 16) after anti-TNF-α treatment despite significant improvement in psoriasis lesions. Circulating levels of sphingomyelins and ceramides shifted in a fatty acid chain length-dependent manner. These alterations were also observed in psoriasis skin lesions and were associated with changes in mRNA levels of ceramide synthases. The lack of S1P response to treatment may have pathobiological implications due to its close relation to the vascular and immune systems. In particular, increased levels of sphingolipids and especially S1P in severe psoriasis patients requiring biological treatment may potentially be associated with cardiovascular comorbidities. The fact that shifts in S1P levels were not ameliorated by anti-TNF-α treatment, despite improvements in the skin lesions, further supports targeting S1P receptors as therapy for severe psoriasis. PMID:26174087

  19. Circulating levels of sphingosine-1-phosphate are elevated in severe, but not mild psoriasis and are unresponsive to anti-TNF-α treatment

    NASA Astrophysics Data System (ADS)

    Checa, Antonio; Xu, Ning; Sar, Daniel G.; Haeggström, Jesper Z.; Ståhle, Mona; Wheelock, Craig E.

    2015-07-01

    Sphingolipids are bioactive molecules with a putative role in inflammation. Alterations in sphingolipids, in particular ceramides, have been consistently observed in psoriatic skin. Herein, we quantified the circulating sphingolipid profile in individuals with mild or severe psoriasis as well as healthy controls. In addition, the effects of anti-TNF-α treatment were determined. Levels of sphingoid bases, including sphingosine-1-phosphate (S1P), increased in severe (P < 0.001 n = 32), but not in mild (n = 32), psoriasis relative to healthy controls (n = 32). These alterations were not reversed in severe patients (n = 16) after anti-TNF-α treatment despite significant improvement in psoriasis lesions. Circulating levels of sphingomyelins and ceramides shifted in a fatty acid chain length-dependent manner. These alterations were also observed in psoriasis skin lesions and were associated with changes in mRNA levels of ceramide synthases. The lack of S1P response to treatment may have pathobiological implications due to its close relation to the vascular and immune systems. In particular, increased levels of sphingolipids and especially S1P in severe psoriasis patients requiring biological treatment may potentially be associated with cardiovascular comorbidities. The fact that shifts in S1P levels were not ameliorated by anti-TNF-α treatment, despite improvements in the skin lesions, further supports targeting S1P receptors as therapy for severe psoriasis.

  20. Novel Oral Therapies for Psoriasis and Psoriatic Arthritis.

    PubMed

    Yiu, Zenas Z N; Warren, Richard B

    2016-06-01

    Several classes of new oral therapy are in use or in development for the treatment of psoriasis. Despite the high efficacy of biologics, new oral therapies remain important as patients generally prefer this mode of administration and they offer an alternative risk-benefit profile. In this review, we discuss the novel modes of action of these drugs, including modulation of cellular pathways involving diverse targets such as Janus kinase, phosphodiesterase 4, sphingosine 1-phosphate, A3 adenosine receptor and rho-associated kinase 2. We review the available evidence around licensed drugs (apremilast) and drugs that are advanced (tofacitinib) or early (ponesimod, baricitinib, peficitinib, INCB039110, CF101, KD025) in the development pipeline. The key limitations of these oral therapies are their modest efficacy profile (apremilast, ponesimod) and the limitations of their safety profile (tofacitinib, ponesimod), while the evidence for the early pipeline drugs are at phase II level only. Potential niches of current unmet needs include apremilast for patients with concomitant psoriatic arthritis, as combination treatments with biologic therapies, and/or for patients in whom multiple biologic therapies have failed due to immunogenicity and secondary inefficacy. The present knowledge gap regarding these novel drugs includes the need for longer clinical trials or observational studies to evaluate safety, and randomised phase III trials for the early pipeline drugs. We conclude that further research and data are necessary to conclusively establish the role of these agents in the current psoriasis treatment paradigm. PMID:26923915

  1. OA01.40. A clinical study to evaluate the efficacy of leech therapy and panchatikta ghrita in the management of psoriasis)

    PubMed Central

    Gond, Pushpa; Rani, Rekha; Shringi, M. K.

    2012-01-01

    Purpose: Modern medical science treats psoriasis with PUVA, corticosteroid, anti-mitotic drugs which gives serious side effects like liver and kindney failure etc. There is a need to discover safe and effective medicine without any side effects for Psoriasis and the role of Leech Therapy (Shodhan) and Panchatikta Ghrita (Shaman Karma) is evaluated in this study. Method: 30 patients were included who matched the clinical signs and symptoms of psoriasis. These patients were randomised into three groups. Group A Only on leech therapy, Group B-Only on panchatikta ghrita and Group C On both leech therapy and panchatikta ghrita Result: Group A showed 45% improvement and group B showed 47% improvement, while group C reported 65% improvement. Conclusion: It can be concluded that shodan(leech application) along with shaman (panchatikta ghrita) is effective in the management of psoriasis as it is safe, cost effective and free from any side effects.

  2. Topical Therapies for Psoriasis: Improving Management Strategies and Patient Adherence.

    PubMed

    Stein Gold, Linda F

    2016-03-01

    Psoriasis is a chronic disease that has a substantial effect on quality of life of patients and often needs long-term treatment. Topical treatments for psoriasis include corticosteroids, vitamin D derivatives, tazarotene, anthralin, tacrolimus, pimecrolimus, and newer formulations of tar. Although many of these treatments are effective, they must be prescribed appropriately and used consistently for a period of weeks to months before clinical evidence of improvement can be seen and patients perceive that the treatment is working. As such, medication dosage/schedule, choice of vehicle, and especially patient adherence to medication are key factors for a treatment to be effective. Addressing patient preferences about treatments and concerns about treatment-related toxicities and managing their expectations represent additional aspects of patient care. Therapies such as calcipotriene and betamethasone dipropionate (Cal/BD) fixed combination foam and new drugs and vehicles continuously enhance the treatment landscape for psoriasis. Because adherence to topical treatment can be a major difficulty, keeping the treatment regimen simple and using new and sophisticated treatment vehicles that are acceptable to patients can likely improve treatment outcomes. PMID:27074696

  3. An update on topical therapies for mild-moderate psoriasis.

    PubMed

    van de Kerkhof, Peter C M

    2015-01-01

    Topical therapies are the mainstream treatment of psoriasis because most patients have mild disease. First-line treatments are vitamin D derivatives and corticosteroids. These treatments are usually given in combination schedules. For topical treatments the selection of the most appropriate vehicle is of major importance, thus improving adherence to the treatment, which frequently is impaired by the complexities of topical therapeutic choices. Evidence for efficacy and safety of topical treatments is readily available for vitamin D treatments and short-term treatment with corticosteroids. However, the scientific evidence for longer-term treatments is limited. Multiple new small molecules are in various stages of development and are reviewed. PMID:25412784

  4. A pilot study examining mindfulness-based cognitive therapy in psoriasis.

    PubMed

    Fordham, B; Griffiths, C E M; Bundy, C

    2015-01-01

    A sub-population of people with psoriasis have strong causal beliefs about stress, high levels of emotional distress (anxiety and depression) and an impaired quality of life (QoL). Mindfulness-based cognitive therapy has been found to reduce levels of stress and distress and to improve QoL. This pilot study in people with psoriasis aimed to test the hypothesis that mindfulness could reduce stress and thereby lessen psoriasis severity, improve QoL and reduce distress. Twenty-nine people with psoriasis (22-70-years old; 16 females; 13 males) were randomised to an eight-week mindfulness treatment as an adjunct to their usual psoriasis therapy or to a control group which continued with usual psoriasis therapy alone. All subjects completed self-reported measurements of psoriasis severity, perceived stress, distress and QoL, at baseline and again post-intervention. The mindfulness group reported statistically lower psoriasis severity (Self-Assessed Psoriasis Area Severity Index; z = 1.96, p = .05) and QoL impairment scores (Dermatology Life Quality Index; z = 2.30, p = .02) than the control group. There was no significant difference between groups on perceived stress (Perceived Stress Scale; z = .07, p = .94) or distress scores (Hospital Anxiety Depression Scale; z = 1.60, p = .11). People with psoriasis who received mindfulness as an adjunct to their usual therapy reported a significant improvement in both psoriasis severity and QoL. These pilot results suggest that a full randomised control trial is justified to examine the effectiveness of mindfulness as an adjunctive treatment for people with psoriasis. PMID:24684520

  5. Methylene blue mediated photodynamic therapy for resistant plaque psoriasis.

    PubMed

    Salah, Manal; Samy, Nevien; Fadel, Maha

    2009-01-01

    Topical treatment of resistant psoriatic plaque stage lesions may be difficult and the systemic therapies seem inappropriate. Therefore, a topical 0.1% methylene blue (MB) hydrogel was prepared and evaluated for percent drug content, drug uniformity, pH, rheological and organoleptic characters such as feel tackiness, grittiness sensation, and transparency in addition to release kinetics study in vitro. The efficiency of the photodynamic therapy (PDT) of MB photo-activated using 565 mW Light emitting diode (LED) 670 nm was evaluated in patients with resistant plaque psoriasis. The gel was evaluated in single blinded study. The patients were subjected to repeated sessions of irradiation, skin biopsies from each patient in the beginning and at the end of the sessions were taken for histopathological studies. Results showed the hydrogel was transparent nongritty and the drug uniformly dispersed with pH=7.2 and viscosity value=25.04 Pa. The drug content was found to be 99.4 +/- 0.15 %. Drug release was following zero order kinetics with rate constant K=0.348 +/- 0.01 and T(1/2) = 0.95 +/- 0.5 hours. Sixteen patients experienced complete clearance of their treated lesions. Skin appeared normal in color, texture, and pliability with no complications indicating the lack of skin sensitivity. Histopathological examinations showed nearly normal epidermis at the end of all sessions. The authors concluded that the prepared hydrogel was safe, stable, and very effective. The results are encouraging to accept MB as a photosensitizer for PDT and as a safe and effective method for treatment of selected cases of resistant localized psoriasis PMID:19180895

  6. Psoriasis

    MedlinePlus

    ... called phototherapy) involves exposing the skin to ultraviolet (UV) light. It works by slowing skin growth and reducing ... doesn’t get better with topical treatments and UV light therapy. Biologic medications work by targeting specific parts ...

  7. The Use of Methotrexate, Alone or in Combination With Other Therapies, for the Treatment of Palmoplantar Psoriasis.

    PubMed

    Wald, Jenna M; Klufas, Daniel M; Strober, Bruce E

    2015-08-01

    Palmoplantar psoriasis is a chronic debilitating type of psoriasis. Treatment options for this disease are poorly studied. This chart review evaluated the use of methotrexate alone and in combination with 7 other systemic therapies in 48 patients with palmoplantar psoriasis. The findings demonstrate that methotrexate is a relatively well-tolerated and effective treatment for palmoplantar psoriasis, amenable as either monotherapy or in combination with other systemic agents. PMID:26267735

  8. Systemic anti-VEGF treatment strongly reduces skin inflammation in a mouse model of psoriasis.

    PubMed

    Schonthaler, Helia B; Huggenberger, Reto; Wculek, Stefanie K; Detmar, Michael; Wagner, Erwin F

    2009-12-15

    Although(,) vascular remodeling is a hallmark of many chronic inflammatory disorders such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis, anti-vascular strategies to treat these conditions have received little attention to date. We investigated the anti-inflammatory activity of systemic blockade of VEGF-A by the inhibitory monoclonal antibody G6-31, employing a therapeutic trial in a mouse model of psoriasis. Simultaneous deletion of JunB and c-Jun (DKO*) in the epidermis of adult mice leads to a psoriasis-like phenotype with hyper- and parakeratosis and increased subepidermal vascularization. Moreover, an inflammatory infiltrate and elevated levels of cytokines/chemokines including TNFalpha, IL-1alpha/beta, IL-6, and the innate immune mediators IL-22, IL-23, IL-23R, and IL-12p40 are detected. Here we show that anti-VEGF antibody treatment of mice already displaying disease symptoms resulted in an overall improvement of the psoriatic lesions leading to a reduction in the number of blood vessels and a significant decrease in the size of dermal blood and lymphatic vessels. Importantly, anti-VEGF-treated mice showed a pronounced reduction of inflammatory cells within the dermis and a normalization of epidermal differentiation. These results demonstrate that systemic blockade of VEGF by an inhibitory antibody might be used to treat patients who have inflammatory skin disorders such as psoriasis. PMID:19995970

  9. Development of a psoriasis-like syndrome following lithium therapy.

    PubMed

    Hanada, K; Tasaki, M; Hashimoto, I; Sone, M; Yamaguchi, T

    1987-12-01

    A correlation between lithium and psoriasis has been observed. In this paper, the case of a 17-yr-old girl is reported who developed psoriatic lesions after administration of lithium carbonate. Further-more, serum lithium levels in some psoriatic patients are disclosed, and induction of psoriasis by lithium in experimental animals is described. Serum lithium levels in 27 patients were significantly higher (p<0.025) than those of controls. Uninvolved parts of skin tissues obtained from three cases of psoriasis were transplanted to nude mice. After supplementing lithium as the chloride, these skin grafts developed the histologic change characteristic of psoriasis. However, the lithium compound by itself did not increase superoxide production of polymorphonuclear leukocytes in psoriasis. PMID:24254819

  10. [Anti DIC therapy].

    PubMed

    Yahata, Mayuko; Sakamoto, Yuichiro

    2016-02-01

    A variety of disorders erratically activate coagulation cascades. The disseminated intravascular coagulation (DIC) is caused by unbalanced activation between coagulation and fibrinolysis. Some of auxiliary treatments for DIC on top of main therapy against causative disease are beneficial in terms of better outcome. The anticoagulation therapy is indicated when an activation of coagulation dominates in DIC caused by sepsis. Whereas in DIC associated with trauma, since balance between coagulation and fibrinolysis collapses drastically in a short period, both anticoagulantion therapy and antifibrinolytic therapy can be utilized depending on clinical conditions. There are quite a few of anti DIC agents in Japan. It is imperative to choose appropriate agents to treat DIC taking their pharmacological properties into account. PMID:26915249

  11. Safety and efficacy of anti-tumor necrosis factors α in patients with psoriasis and chronic hepatitis C

    PubMed Central

    Salvi, Monica; Macaluso, Laura; Luci, Cecilia; Mattozzi, Carlo; Paolino, Giovanni; Aprea, Yvonne; Calvieri, Stefano; Richetta, Antonio Giovanni

    2016-01-01

    Up to date, in literature, it is still debated the role of anti-tumor necrosis factors (TNF)-α treatments in hepatitis C virus (HCV) patients. TNF-α performs a lot of functions, it is an important pro-inflammatory cytokine and it is involved in the host’s immunity. Since TNF-α is implicated in the apoptotic signaling pathway of hepatocytes infected by HCV, anti TNF-α therapy may increase the risk of viral replication or their reactivation. However the treatment of anti TNF-α could have a healthful role because TNF-α appears to be engaged in the pathogenesis of liver fibrosis, inducing apoptotic pathways. We describe the case of a patient with plaque-type psoriasis and concomitant chronic HCV, who was treated successfully with anti-TNF agents simultaneously to cyclosporine without sign of reactivation of HCV and increase of liver enzymes. Our personal experience shows that anti-TNF-α agents are not only effective but also safe. Furthermore the combination therapy of cyclosporine and anti-TNF-α appears to be well-tolerated and able to reduce the amount of liver enzymes as well as HCV-viral-load. However systematic, large-scale studies with long follow-ups will be needed to confirm our results, in association with close liver function monitoring. PMID:26881191

  12. Topical therapy for psoriasis: a promising future. Focus on JAK and phosphodiesterase-4 inhibitors.

    PubMed

    Rafael, Adilia; Torres, Tiago

    2016-01-01

    Psoriasis is a common, chronic and disabling skin disorder affecting approximately 2% of the population, associated with significant negative impact on the patient's quality of life. Approximately 80% of those affected with psoriasis have mild-to-moderate forms and are usually treated with topical therapy, whereas phototherapy and systemic therapies are used for those with severe disease. In the past three decades, the major advances in psoriasis therapy have been in systemic agents for the treatment of moderate-to-severe psoriasis, particularly new immunomodulatory and biological molecules, while topical therapies have remained relatively unchanged over the past decades. Indeed, topical corticosteroids and vitamin D3 analogs are still the gold standard of therapy for mild-to-moderate psoriasis. Thus, there is a need to develop new and more effective topical agents in the short and long term, with a better efficacy and safety profile than corticosteroids and vitamin D3 analogs. Over the past five years, investigation into topical therapy has expanded, with exciting new drugs being developed. Preliminary results of these emerging agents that selectively target disease-defining pathogenic pathways seem to be promising, although long-term and large-scale studies assessing safety and efficacy are still lacking. The aim of this article was to review the clinical and research data of some emerging topical agents, focusing on Janus kinase-signal transducer and activator of transcription and phosphodiesterase type 4 inhibitors, which are currently being investigated. PMID:26552963

  13. Providing Guidance for Patients With Moderate-to-Severe Psoriasis Who Are Candidates for Biologic Therapy

    PubMed Central

    Aldredge, Lakshi M.; Young, Melodie S.

    2016-01-01

    ABSTRACT Psoriasis is a chronic, immune-mediated disease characterized by itchy, scaly, and often painful plaques in the skin. Psoriasis can have significant psychosocial burdens and increased risks for numerous comorbidities, including diabetes, hypertension, and cardiovascular disease, particularly in patients with moderate-to-severe disease. Dermatology nurse practitioners and physician assistants are an important part of the healthcare team, contributing to all aspects of psoriasis management. This review reinforces the unique aspects of care that nurse practitioners and physician assistants provide to patients with psoriasis, such as facilitating conversations about managing disease, setting appropriate expectations, and considering treatment options, including when treatment response or tolerability is suboptimal. The importance of relationship building is stressed. Patient management topics discussed include helpful tips about assessing treatment options, initiating biologic therapy, optimizing patient adherence, and managing comorbidities. Also reviewed are how to deal with common barriers including lack of knowledge about psoriasis or making healthy lifestyle changes, fear of injections or side effect risks, lack of health insurance, and concerns about treatment costs. Overall, by forming meaningful relationships and engaging patients in their psoriasis care, nurse practitioners and physician assistants can help to optimize clinical efficacy outcomes and consistently manage moderate-to-severe psoriasis and its comorbidities over the patient’s life course. PMID:27004085

  14. Update on the mechanisms and efficacy of biological therapies for psoriasis.

    PubMed

    Koo, John; Khera, Pooja

    2005-05-01

    Biologically based agents (biologics) are novel therapeutic options in the treatment of moderate-to-severe psoriasis. Unlike traditional systemic anti-psoriatic drugs, which are chemically synthesized, these agents are unique in that they are derived from living organisms and hence called "biologics." In addition, they are the first group of "custom-designed" molecules that precisely target steps in the pathogenesis of psoriasis. The specificity of these biologics can theoretically avoid the side effects of the prebiologically developed systemic agents including the effects of hepatotoxicity, nephrotoxicity, and bone marrow suppression. However, there is also a tendency for a more precisely targeted agent to have a less overall efficacy. Due to the varying efficacies and high costs of the new biologic agents that are currently approved for psoriasis in the United States, the precise way they fit into the range of treatments for moderate-to-severe psoriasis should be defined pending future clinical experiences. PMID:15862940

  15. Skin blood flow in psoriasis during Goeckerman or beech tar therapy.

    PubMed

    Staberg, B; Klemp, P

    1984-01-01

    Skin blood flow (SBF) was measured by the laser Doppler technique in lesional and clinically normal skin of 8 patients with psoriasis vulgaris during Goeckerman or beech tar therapy. The SBF measurements were performed before therapy and 1, 2, and 3-4 weeks after treatment was initiated. The results were compared to a clinical psoriasis index based on the objective assessment of infiltration, erythema, and scaling of the psoriatic plaques. The pre-treatment value of SBF in lesional skin was about 9 times higher than that of clinically normal skin. During therapy SBF of involved skin decreased rapidly approaching that of uninvolved skin after 3-4 weeks. Furthermore, there was a significant linear correlation between the SBF values and the clinical psoriasis index. It is concluded that SBF in psoriatic lesions decreases significantly during Goeckerman or beech tar therapy, and that this variable might be used to obtain a quantitative measure of the disease activity. PMID:6209892

  16. Manifestation of palmoplantar pustulosis during or after infliximab therapy for plaque-type psoriasis: report on five cases

    PubMed Central

    Thaci, Diamant; Mohr, Johannes; Pätzold, Sylvie; Bertsch, Hans Peter; Krüger, Ullrich; Reich, Kristian

    2008-01-01

    Infliximab is a monoclonal antibody directed against TNF-α. It has been approved for use in rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriatic arthritis and plaque-type psoriasis. In case reports, positive effects on pustular variants of psoriasis have also been reported. However, paradoxically, manifestation of pustular psoriasis and plaque-type psoriasis has been reported in patients treated with TNF antagonists including infliximab for other indications. Here, we report on 5 patients with chronic plaque-type psoriasis who developed palmoplantar pustulosis during or after discontinuation of infliximab therapy. In two of the five cases, manifestation of palmoplantar pustulosis was not accompanied by worsening of plaque-type psoriasis. Possibly, site-specific factors or a differential contribution of immunological processes modulated by TNF inhibitors to palmoplantar pustulosis and plaque-type psoriasis may have played a role. PMID:18239925

  17. Manifestation of palmoplantar pustulosis during or after infliximab therapy for plaque-type psoriasis: report on five cases.

    PubMed

    Mössner, Rotraut; Thaci, Diamant; Mohr, Johannes; Pätzold, Sylvie; Bertsch, Hans Peter; Krüger, Ullrich; Reich, Kristian

    2008-03-01

    Infliximab is a monoclonal antibody directed against TNF-alpha. It has been approved for use in rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriatic arthritis and plaque-type psoriasis. In case reports, positive effects on pustular variants of psoriasis have also been reported. However, paradoxically, manifestation of pustular psoriasis and plaque-type psoriasis has been reported in patients treated with TNF antagonists including infliximab for other indications. Here, we report on 5 patients with chronic plaque-type psoriasis who developed palmoplantar pustulosis during or after discontinuation of infliximab therapy. In two of the five cases, manifestation of palmoplantar pustulosis was not accompanied by worsening of plaque-type psoriasis. Possibly, site-specific factors or a differential contribution of immunological processes modulated by TNF inhibitors to palmoplantar pustulosis and plaque-type psoriasis may have played a role. PMID:18239925

  18. [Drug-related psoriasis].

    PubMed

    Piérard-Franchimont, C; Piérard, G E

    2012-03-01

    Psoriasis is a common genetic disorder that may be initiated (drug-induced psoriasis) or exacerbated (drug-triggered psoriasis) by some drug intakes. Beta-blockers, lithium, some antimelarial drugs, non steroidal anti-inflammatory agents and tetracyclines are recognized to influence the clinical course of psoriasis. Other drugs are likely or possibly involved in this process. PMID:22611830

  19. [Pustular psoriasis].

    PubMed

    Weisenseel, P; Wilsmann-Theis, D; Kahl, C; Reich, K; Mössner, R

    2016-06-01

    A number of pustular skin diseases share clinical, pathogenetic, and epidemiological aspects with plaque-type psoriasis, and their classification as a separate clinical entity or as a subtype of psoriasis remains controversial, which is also reflected in the multitude of their names. They include generalized pustular psoriasis with its subtypes, acrodermatitis continua suppurativa (Hallopeau), acute pustulosis palmopantaris, palmoplantar pustular psoriasis, and pustular variants of a mostly TNF-blocker triggered paradoxical psoriasiform dermatitis. In this article, the epidemiology, clinical picture, pathogenesis, genetics, and therapy of these pustular skin diseases are described. PMID:27240667

  20. No Significant Reduction of Circulating Endothelial-Derived and Platelet-Derived Microparticles in Patients with Psoriasis Successfully Treated with Anti-IL12/23.

    PubMed

    Ho, Ji-Chen; Lee, Chih-Hung; Lin, Shang-Hung

    2016-01-01

    Psoriasis is associated with atherosclerosis, in which circulating microparticles play an important role. In severe psoriasis, there was an increase of endothelial- and platelet- microparticles which could be decreased by anti-TNFα. However, whether anti-IL-12/23 treatment would decrease the level of microparticles remains unknown. Our study showed that, despite the clinical improvement of psoriasis after IL-12/13 blockage, the increased levels of circulating CD41a and CD31 microparticles were unchanged after anti-IL-12/23. This result suggested that anti-IL12/23 treatment may not alter the development of cardiovascular disease in patients with psoriasis. PMID:27144162

  1. Biologic therapy improves psoriasis by decreasing the activity of monocytes and neutrophils.

    PubMed

    Yamanaka, Keiichi; Umezawa, Yoshinori; Yamagiwa, Akisa; Saeki, Hidehisa; Kondo, Makoto; Gabazza, Esteban C; Nakagawa, Hidemi; Mizutani, Hitoshi

    2014-08-01

    Therapy with monoclonal antibodies to tumor necrosis factor (TNF)-α and the interleukin (IL)-12/23 p40 subunit has significantly improved the clinical outcome of patients with psoriasis. These antibodies inhibit the effects of the target cytokines and thus the major concern during their use is the induction of excessive immunosuppression. Recent studies evaluating the long-term efficacy and safety of biologic therapy in psoriasis have shown no significant appearance of serious adverse effects including infections and malignancies. However, the immunological consequence and the mechanism by which the blockade of a single cytokine by biologics can successfully control the activity of psoriasis remain unclear. In the current study, we investigated the effect of biologic therapy on cytokine production of various lymphocytes and on the activity of monocytes and neutrophils in psoriatic patients. Neutrophils, monocytes and T cells were purified from heparinized peripheral venous blood by Ficoll density gradient centrifugation, and γ-interferon, TNF-α and IL-17 production from lymphocytes was measured by flow cytometer. The activation maker of neutrophils and the activated subsets of monocytes were also analyzed. Biologic therapy induced no significant changes in the cytokine production by lymphocytes from the skin and gut-homing T cells. However, neutrophil activity and the ratio of activated monocyte population increased in severely psoriatic patients were normalized in psoriatic patients receiving biologic therapy. The present study showed that biologic therapy ameliorates clinical symptoms and controls the immune response in patients with psoriasis. PMID:25099154

  2. Using Imiquimod-Induced Psoriasis-Like Skin as a Model to Measure the Skin Penetration of Anti-Psoriatic Drugs

    PubMed Central

    Lin, Yin-Ku; Yang, Sien-Hung; Chen, Chin-Chuan; Kao, Hsiao-Ching; Fang, Jia-You

    2015-01-01

    Objective Psoriasis is a chronic inflammatory skin disease and topical therapy remains a key role for treatment. The aim of this study is to evaluate the influence of psoriasis-like lesions on the cutaneous permeation of anti-psoriatic drugs. Methods We first set up imiquimod-induced dermatitis in mice that closely resembles human psoriasis lesions. The development of the lesions is based on the IL-23/IL17A axis for phenotypical and histological characteristics. Four drugs, 5-aminolevulinic acid (ALA), tacrolimus, calcipotriol, and retinoic acid, were used to evaluate percutaneous absorption. Results The most hydrophilic molecule, ALA, revealed the greatest enhancement on skin absorption after imiquimod treatment. Imiquimod increased the skin deposition and flux of ALA by 5.6 to 14.4-fold, respectively, compared to normal skin. The follicular accumulation of ALA was also increased 3.8-fold. The extremely lipophilic drug retinoic acid showed a 1.7- and 3.8-fold increase in skin deposition and flux, respectively. Tacrolimus flux was enhanced from 2 to 21 μg/cm2/h by imiquimod intervention. However, imiquimod did not promote skin deposition of this macrolide. The lipophilicity, but not the molecular size, dominated drug permeation enhancement by psoriatic lesions. The in vivo percutaneous absorption of ALA and rhodamine B examined by confocal microscopy confirmed the deficient resistance of epidermal barrier for facilitating cutaneous delivery of drugs via psoriasis-like skin. Conclusion We established the topical delivery profiles of anti-psoriatic drugs via imiquimod-treated psoriasis-like skin. PMID:26355594

  3. Paradoxical psoriasiform reactions to anti-TNFα drugs are associated with genetic polymorphisms in patients with psoriasis.

    PubMed

    Cabaleiro, T; Prieto-Pérez, R; Navarro, R; Solano, G; Román, M; Ochoa, D; Abad-Santos, F; Daudén, E

    2016-08-01

    Paradoxical psoriasiform reactions to anti-tumor necrosis factor α (TNFα) agents have been described. We aimed to study the association between these reactions and polymorphisms in genes previously associated with psoriasis or other autoimmune diseases. A total of 161 patients with plaque-type psoriasis treated with anti-TNFα drugs were genotyped for 173 single-nucleotide polymorphisms (SNPs) using the Illumina Veracode genotyping platform. Among the 161 patients, 25 patients developed a paradoxical psoriasiform reaction consisting of a change in morphology, mostly to guttate psoriasis (88%). These lesions developed 9.20±13.52 months after initiating treatment, mainly with etanercept (72%). Psoriasis type and a Psoriasis Area and Severity Index (PASI) 75 response to treatment were not associated with lesions. Multivariate logistic regression revealed that five SNPs (rs11209026 in IL23R, rs10782001 in FBXL19, rs3087243 in CTLA4, rs651630 in SLC12A8 and rs1800453 in TAP1) were associated with paradoxical reactions. This is the first study to show an association between genetic polymorphisms and paradoxical reactions in patients with psoriasis treated with anti-TNFα drugs.The Pharmacogenomics Journal advance online publication, 21 July 2015; doi:10.1038/tpj.2015.53. PMID:26194362

  4. UV doses and skin effects during psoriasis climate therapy

    NASA Astrophysics Data System (ADS)

    Randeberg, Lise L.; Hernandez-Palacios, Julio; Lilleeng, Mila; Nilsen, Lill Tove; Krogstad, Anne-Lene

    2011-03-01

    Psoriasis is a common autoimmune disease with inflammatory symptoms affecting skin and joints. One way of dealing with psoriasis is by controlled solar UV exposure treatment. However, this treatment should be optimized to get the best possible treatment effect and to limit negative side effects such as erythema and an increased risk of skin cancer. In this study 24 patients at Valle Marina Treatment Center in Gran Canaria were monitored throughout a treatment period of three weeks starting at the beginning of November. The total UV dose to the location was monitored by UV-meters placed on the roof of the treatment centere, and the patients wore individual film dosimeters throughout the treatment period. Skin parameters were accessed by reflection spectroscopy (400-850nm). This paper presents preliminary findings from the skin measurements in the visible part of the spectrum, such as blood oxygenation, erythema and melanin indexes. Reflection spectroscopy was found to be a good tool for such treatment monitoring.

  5. Itolizumab - a humanized anti-CD6 monoclonal antibody with a better side effects profile for the treatment of psoriasis.

    PubMed

    Menon, Roshni; David, Brinda G

    2015-01-01

    Management of psoriasis is a challenge to the treating physician. The chronic inflammatory state of psoriasis with exacerbations and remissions necessitate "on-and-off" treatment schedules. The safety profiles of drugs and tolerability issues for patients are important factors to be considered during treatment. Various biological agents targeting T-cells and the inflammatory cytokines are available for systemic treatment of psoriasis. However, major causes of concern while using these drugs are risk of susceptibility to infection and development of anti-drug antibodies, which will affect the pharmacokinetic properties, efficacy, and safety profile of the drug. Itolizumab, a humanized anti-CD6 monoclonal antibody, is a new molecule that acts by immunomodulating the CD6 molecule. CD6 is a co-stimulatory molecule required for optimal T-cell stimulation by the antigen-presenting cells. This step is crucial in T-cell proliferation to form Th1 and Th17 cells, which play a major role in the pathogenesis of psoriasis. This article deals with the properties of Itolizumab and its role in the treatment of psoriasis. Based on the available published data, Itolizumab seems to have a better adverse effects profile and at the same time comparatively less efficacy when compared to other biological agents available for treating psoriasis. Larger studies with longer duration are required to clearly depict the long-term side effects profile. PMID:25945063

  6. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 3. Guidelines of care for the management and treatment of psoriasis with topical therapies.

    PubMed

    Menter, Alan; Korman, Neil J; Elmets, Craig A; Feldman, Steven R; Gelfand, Joel M; Gordon, Kenneth B; Gottlieb, Alice; Koo, John Y M; Lebwohl, Mark; Lim, Henry W; Van Voorhees, Abby S; Beutner, Karl R; Bhushan, Reva

    2009-04-01

    Psoriasis is a common, chronic, inflammatory, multi-system disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this third of 6 sections of the guidelines of care for psoriasis, we discuss the use of topical medications for the treatment of psoriasis. The majority of patients with psoriasis have limited disease (<5% body surface area involvement) and can be treated with topical agents, which generally provide a high efficacy-to-safety ratio. Topical agents may also be used adjunctively for patients with more extensive psoriasis undergoing therapy with either ultraviolet light, systemic or biologic medications. However, the use of topical agents as monotherapy in the setting of extensive disease or in the setting of limited, but recalcitrant, disease is not routinely recommended. Treatment should be tailored to meet individual patients' needs. We will discuss the efficacy and safety of as well as offer recommendations for the use of topical corticosteroids, vitamin D analogues, tazarotene, tacrolimus, pimecrolimus, emollients, salicylic acid, anthralin, coal tar, as well as combination therapy. PMID:19217694

  7. Guidelines of care for the management of psoriasis and psoriatic arthritis Section 3. Guidelines of care for the management and treatment of psoriasis with topical therapies

    SciTech Connect

    Menter, A.; Korman, N.J.; Elmets, C.A.; Feldman, S.R.; Gelfand, J.M.; Gordon, K.B.; Gottlieb, A.; Koo, J.Y.M.; Lebwohl, M.; Lim, H.W.; Van Voorhees, A.S.; Beutner, K.R.; Bhushan, R.

    2009-04-15

    Psoriasis is a common, chronic, inflammatory, multi-system disease with predominantly skin and joint manifestations affecting approximately 2% of the Population. In this third of 6 sections of the guidelines of care for psoriasis, we discuss the use of topical medications for the treatment of psoriasis. The majority of patients with psoriasis have limited disease (<5% body surface area involvement) and can be treated with topical agents, which generally provide a high efficacy-to-safety ratio. Topical agents may also be used adjunctively for patients with more extensive psoriasis undergoing therapy with either ultraviolet light, systemic or biologic medications. However, the use of topical agents as monotherapy in the setting of extensive disease or in the setting of limited, but recalcitrant, disease is not routinely recommended. Treatment should be tailored to meet individual patients' needs. We will discuss the efficacy and safety of as well as offer recommendations for the use of topical corticosteroids, vitamin D analogues, tazarotene, tacrolimus, pimecrolimus, emollients, salicylic acid, anthralin, coal tar, as well as combination therapy.

  8. A Patient with Refractory Psoriasis Who Developed Sebaceous Carcinoma on the Neck during Cyclosporine Therapy and Showed Rapid Progression

    PubMed Central

    Shima, Tomoko; Yamamoto, Yuki; Okuhira, Hisako; Mikita, Naoya; Furukawa, Fukumi

    2016-01-01

    We report a patient who developed sebaceous carcinoma on the neck during therapy with immunosuppressive agents (cyclosporine, corticosteroid, methotrexate) for refractory psoriasis vulgaris, which showed rapid enlargement, leading to a fatal outcome. Multiple-organ metastases were detected. Weekly carboplatin + paclitaxel therapy resulted in the disappearance of tumor cells, but the patient died of febrile neutropenia. The development of sebaceous carcinoma is rare among psoriasis patients receiving immunosuppressive agents including cyclosporine. PMID:27462222

  9. A Patient with Refractory Psoriasis Who Developed Sebaceous Carcinoma on the Neck during Cyclosporine Therapy and Showed Rapid Progression.

    PubMed

    Shima, Tomoko; Yamamoto, Yuki; Okuhira, Hisako; Mikita, Naoya; Furukawa, Fukumi

    2016-01-01

    We report a patient who developed sebaceous carcinoma on the neck during therapy with immunosuppressive agents (cyclosporine, corticosteroid, methotrexate) for refractory psoriasis vulgaris, which showed rapid enlargement, leading to a fatal outcome. Multiple-organ metastases were detected. Weekly carboplatin + paclitaxel therapy resulted in the disappearance of tumor cells, but the patient died of febrile neutropenia. The development of sebaceous carcinoma is rare among psoriasis patients receiving immunosuppressive agents including cyclosporine. PMID:27462222

  10. Long-term risks of psoralen and UV-A therapy for psoriasis

    SciTech Connect

    Farber, E.M.; Abel, E.A.; Cox, A.J.

    1983-05-01

    It has been more than eight years since photochemotherapy with methoxsalen and UV-A (psoralen and UV-A (PUVA)) was introduced for the treatment of psoriasis. This treatment remained under investigation until May 1982 because of concerns about possible chronic toxic effects. With recent Food and Drug Administration approval of PUVA therapy for severe psoriasis, strict drug labeling for administration and patient use and continued monitoring of side effects have become essential. The full effects of PUVA in regard to carcinogenicity, prematurelly induced aging of the skin, pigmentary changes, immunologic alterations, and ocular side effects are still unknown. A review of the risks of PUVA therapy is presented, with the aim of maintaining a proper perspective for its limited use in treating selected patients.

  11. Iatrogenic Cushing's Syndrome After Topical Steroid Therapy for Psoriasis

    PubMed Central

    Sahıp, Birsen; Celık, Mehmet; Ayturk, Semra; Kucukarda, Ahmet; Mert, Onur; Dıncer, Nejla; Guldıken, Sıbel; Tugrul, Armagan

    2016-01-01

    Glucocorticoids are used for the treatment of many diseases, such as inflammatory, allergic, autoimmune, and neoplastic diseases. They can be used in the form of topical, oral, inhalable, rectal, and intra-articular agents. Many topical steroid-related iatrogenic Cushing's syndrome cases affecting especially children have been reported in the literature. Topical steroid-related Cushing's syndrome is rarely seen in adults. In this report, we present the case of a 32-year-old male patient with iatrogenic Cushing's syndrome related to long-term clobetasol propionate treatment for psoriasis. In the context of such treatment, the glucocorticoid withdrawal problem has to be overcome. At present there is no consensus on steroid withdrawal. Patients on long-term glucocorticoid treatment must be evaluated for potential adverse effects and withdrawal symptoms by their physician and their endocrinologist. PMID:26955131

  12. Iatrogenic Cushing's Syndrome After Topical Steroid Therapy for Psoriasis.

    PubMed

    Sahıp, Birsen; Celık, Mehmet; Ayturk, Semra; Kucukarda, Ahmet; Mert, Onur; Dıncer, Nejla; Guldıken, Sıbel; Tugrul, Armagan

    2016-01-01

    Glucocorticoids are used for the treatment of many diseases, such as inflammatory, allergic, autoimmune, and neoplastic diseases. They can be used in the form of topical, oral, inhalable, rectal, and intra-articular agents. Many topical steroid-related iatrogenic Cushing's syndrome cases affecting especially children have been reported in the literature. Topical steroid-related Cushing's syndrome is rarely seen in adults. In this report, we present the case of a 32-year-old male patient with iatrogenic Cushing's syndrome related to long-term clobetasol propionate treatment for psoriasis. In the context of such treatment, the glucocorticoid withdrawal problem has to be overcome. At present there is no consensus on steroid withdrawal. Patients on long-term glucocorticoid treatment must be evaluated for potential adverse effects and withdrawal symptoms by their physician and their endocrinologist. PMID:26955131

  13. Biologic therapies for moderate to severe psoriasis are not interchangeable.

    PubMed

    Puig, L

    2014-06-01

    Health care managers and hospital pharmacists are increasingly compelling prescribers to use medication substitutes. This policy becomes particularly evident when the agents are biologics with shared indications based on their assumed clinical equivalence and efficiency (cost-effectiveness), and in these cases the involvement of clinicians in decision making is often minimal or nonexistent. Lacking head-to-head clinical trials comparing various drugs, the prescriber can use indirect comparisons to define 2 or more agents as clinically equivalent therapeutic alternatives. This denomination of clinical equivalence does not imply that 2 such medications are truly therapeutically equivalent, or therapeutic equivalents, as this type of equivalence is defined by the absence of statistically significant differences between the drugs on all measures of effect in most patients, meaning that neither one is preferable to the other in different situations. Although real patients are not entirely comparable to those in clinical trials, the choice of a biologic agent to treat psoriasis is largely based on the findings of such trials. A recently published meta-analysis shows that not all the biologics currently available to treat moderate to severe psoriasis can be considered therapeutic equivalents, in spite of the authors' claim to the contrary; indeed, infliximab and etanercept can in no way be considered equivalent therapeutic alternatives based on the data provided. Biologics do display real differences with respect to efficacy at different time points and in the time required to onset of effect. In any case, therapeutic decisions should be made by an experienced clinician and tailored to each individual patient. PMID:24094516

  14. Apremilast and Secukinumab Combined Therapy in a Patient With Recalcitrant Plaque Psoriasis.

    PubMed

    Rothstein, Brooke E; McQuade, Brianna; Greb, Jacqueline E; Goldminz, Ari M; Gottlieb, Alice B

    2016-05-01

    We report a 67-year-old Caucasian man with a long-term history of recalcitrant plaque psoriasis and psoriatic arthritis who was initiated on a treatment regimen of apremilast and secukinumab after failing multiple topical, photo, and systemic therapies. This combination provided significant skin improvement with minimal drug side effects.

    J Drugs Dermatol. 2016;15(5):648-649. PMID:27168275

  15. Estimated UV doses to psoriasis patients during climate therapy at Gran Canaria in March 2006

    NASA Astrophysics Data System (ADS)

    Nilsen, L. T. N.; Søyland, E.; Krogstad, A. L.

    2008-01-01

    Psoriasis is a chronic inflammatory disease involving about 2-3% of the Norwegian population. Sun exposure has a positive effect on most psoriasis lesions, but ultraviolet (UV) radiation also causes a direct DNA damage in the skin cells and comprises a carcinogenic potential. UV exposure on the skin causes a local as well as a systemic immune suppressive effect, but the relation between sun exposure and these biological effects is not well known. In March 2006 a study was carried out to investigate possible therapeutic outcome mechanisms in 20 psoriasis patients receiving climate therapy at Gran Canaria. This paper presents estimates of their individual skin UV-doses based on UV measurements and the patients' diaries with information on time spent in the sun. On the first day of exposure the patients received on average 5.1 Standard Erythema Doses (SED: median=4.0 SED, range 2.6-10.3 SED) estimated to the skin. During the 15 days study they received 165.8 SED (range 104.3-210.1 SED). The reduction in PASI score was 72.8% on average, but there was no obvious relation between the improvement and the UV dose. The UV doses were higher than those found from climate therapy studies at other locations. It seems beneficial to use more strict exposure schedules that consider the available UV irradiance, depending on time of the day, time of the year and weather conditions.

  16. Psoriasis of the nail: anatomy, pathology, clinical presentation, and a review of the literature on therapy.

    PubMed

    Jiaravuthisan, Michael M; Sasseville, Denis; Vender, Ronald B; Murphy, Francis; Muhn, Channy Y

    2007-07-01

    Psoriasis is a chronic skin disease that affects millions of people throughout the world. Even though cutaneous signs and symptoms are the most common clinical manifestations, the nails can be involved in up to 50% of cases, and their involvement remains an important yet often overlooked aspect of the disease. There is a broad spectrum of nail dystrophies associated with psoriasis, ranging from the common pitting and loosening of the nail plate to the less frequent discoloration and splinter hemorrhages seen in the nail bed. This article discusses the normal anatomy and embryology of the nail unit as well as the current understanding of the pathogenesis of the disease. It also provides an extensive review of the existing literature with respect to psoriatic nail therapy. Although there have been many recent advances in the treatment of the cutaneous form of the disease-most notably in the field of immunotherapies-the options for nail psoriasis are far more limited. While a number of treatment alternatives currently exist for nail disease, the general paucity of clear evidence regarding these choices often makes it difficult to select the most efficient, safe, and optimal treatment for the patient. Even though the current literature has shown some support for the use of topical, intralesional, radiation, systemic, and combination therapies for nail psoriasis, the available studies lack sufficient power to extrapolate a standardized therapeutic regimen. Therefore, until better-documented evidence validating the treatment options emerges within the literature, clinicians and patients are left with a vague and relatively unproven approach to psoriatic nail disease. PMID:17572277

  17. Cost-of-Illness in Psoriasis: Comparing Inpatient and Outpatient Therapy

    PubMed Central

    Steinke, Sabine I. B.; Peitsch, Wiebke K.; Ludwig, Alexander; Goebeler, Matthias

    2013-01-01

    Treatment modalities of chronic plaque psoriasis have dramatically changed over the past ten years with a still continuing shift from inpatient to outpatient treatment. This development is mainly caused by outpatient availability of highly efficient and relatively well-tolerated systemic treatments, in particular BioLogicals. In addition, inpatient treatment is time- and cost-intense, conflicting with the actual burst of health expenses and with patient preferences. Nevertheless, inpatient treatment with dithranol and UV light still is a major mainstay of psoriasis treatment in Germany. The current study aims at comparing the total costs of inpatient treatment and outpatient follow-up to mere outpatient therapy with different modalities (topical treatment, phototherapy, classic systemic therapy or BioLogicals) over a period of 12 months. To this end, a retrospective cost-of-illness study was conducted on 120 patients treated at the University Medical Centre Mannheim between 2005 and 2006. Inpatient therapy caused significantly higher direct medical, indirect and total annual costs than outpatient treatment (13,042 € versus 2,984 €). Its strong influence on cost levels was confirmed by regression analysis, with total costs rising by 104.3% in case of inpatient treatment. Patients receiving BioLogicals produced the overall highest costs, whereas outpatient treatment with classic systemic antipsoriatic medications was less cost-intense than other alternatives. PMID:24194911

  18. Immunological and histological evaluation of clinical samples from psoriasis patients treated with anti-CD6 itolizumab

    PubMed Central

    Aira, Lazaro E; López-Requena, Alejandro; Fuentes, Dasha; Sánchez, Liset; Pérez, Teresita; Urquiza, Aleida; Bautista, Heber; Falcón, Leopoldina; Hernández, Patricia; Mazorra, Zaima

    2014-01-01

    Psoriasis is a chronic inflammatory disease with a prevalence of approximately 2–3% in the general population. The majority of diagnosed patients have plaque psoriasis, and about 20% have moderate-to-severe disease. Itolizumab, a new monoclonal antibody specific for the CD6 molecule mainly expressed on T lymphocytes, has demonstrated to inhibit in vitro ligand-induced proliferation and pro-inflammatory cytokine production. We assessed the immunological and histopathological effect of the antibody using clinical samples taken from 26 patients with moderate-to-severe psoriasis included in a clinical trial. The precursor frequency of lymphocytes activated with anti-CD2/CD3/CD28 beads, as well as the number of interferon (IFN)-γ-secreting T cells after stimulation, were measured at different time points of the study. Serum cytokine levels and anti-idiotypic antibody response to itolizumab were also evaluated. Additionally, lymphocyte infiltration and epidermis hyperplasia were studied in five patients. A significant reduction in T cell proliferation capacity and number of IFN-γ-producing T cells was found in treated patients. Serum levels of interleukin-6, tumor necrosis factor and IFN-γ showed an overall trend toward reduction. No anti-idiotypic antibody response was detected. A significant reduction in the epidermis hyperplasia was observed in analyzed patients. These results support the relevance of the CD6 molecule as a therapeutic target for the treatment of this disease. PMID:24594862

  19. LC-MS metabolomics of psoriasis patients reveals disease severity-dependent increases in circulating amino acids that are ameliorated by anti-TNFα treatment.

    PubMed

    Kamleh, Muhammad Anas; Snowden, Stuart G; Grapov, Dmitry; Blackburn, Gavin J; Watson, David G; Xu, Ning; Ståhle, Mona; Wheelock, Craig E

    2015-01-01

    Psoriasis is an immune-mediated highly heterogeneous skin disease in which genetic as well as environmental factors play important roles. In spite of the local manifestations of the disease, psoriasis may progress to affect organs deeper than the skin. These effects are documented by epidemiological studies, but they are not yet mechanistically understood. In order to provide insight into the systemic effects of psoriasis, we performed a nontargeted high-resolution LC-MS metabolomics analysis to measure plasma metabolites from individuals with mild or severe psoriasis as well as healthy controls. Additionally, the effects of the anti-TNFα drug Etanercept on metabolic profiles were investigated in patients with severe psoriasis. Our analyses identified significant psoriasis-associated perturbations in three metabolic pathways: (1) arginine and proline, (2) glycine, serine and threonine, and (3) alanine, aspartate, and glutamate. Etanercept treatment reversed the majority of psoriasis-associated trends in circulating metabolites, shifting the metabolic phenotypes of severe psoriasis toward that of healthy controls. Circulating metabolite levels pre- and post-Etanercept treatment correlated with psoriasis area and severity index (PASI) clinical scoring (R(2) = 0.80; p < 0.0001). Although the responsible mechanism(s) are unclear, these results suggest that psoriasis severity-associated metabolic perturbations may stem from increased demand for collagen synthesis and keratinocyte hyperproliferation or potentially the incidence of cachexia. Data suggest that levels of circulating amino acids are useful for monitoring both the severity of disease as well as therapeutic response to anti-TNFα treatment. PMID:25361234

  20. Very low-calorie ketogenic diet may allow restoring response to systemic therapy in relapsing plaque psoriasis.

    PubMed

    Castaldo, Giuseppe; Galdo, Giovanna; Rotondi Aufiero, Felice; Cereda, Emanuele

    2016-01-01

    Psoriasis is a chronic disease associated with overweight/obesity and related cardiometabolic complications. The link between these diseases is likely the inflammatory background associated with adipose tissue, particularly the visceral one. Accordingly, previous studies have demonstrated that in the long-term weight loss may improve the response to systemic therapies. We report a case report of a woman in her 40s suffering from relapsing moderate-to-severe plaque psoriasis and obesity-related metabolic syndrome, in whom adequate response to ongoing treatment with biological therapy (adalimumab) was restored after only 4 weeks of very low-calorie, carbohydrate-free (ketogenic), protein-based diet. Accordingly, through rapid and consistent weight loss, very low calorie ketogenic diet may allow restoring a quick response to systemic therapy in a patient suffering from relapsing psoriasis. This intervention should be considered in overweight/obese patients before the rearrangement of systemic therapy. Nonetheless, studies are required to evaluate whether very low calorie ketogenic diets should be preferred to common low-calorie diets to improve the response to systemic therapy at least in patients with moderate-to-severe psoriasis. PMID:26559897

  1. Possible paraneoplastic syndrome case of bullous pemphigoid with immunoglobulin G anti-BP180 C-terminal domain antibodies associated with psoriasis and primary macroglobulinemia.

    PubMed

    Maki, Nobuki; Demitsu, Toshio; Umemoto, Naoka; Nagashima, Kazutaka; Nakamura, Toshinobu; Kakurai, Maki; Nakamura, Satoshi; Yamada, Tomoko; Ishii, Norito; Hashimoto, Takashi

    2016-05-01

    A 61-year-old Japanese man developed bullous skin lesions during topical therapy for psoriasis vulgaris. Physical examination demonstrated numerous tense bullae and scaly erythemas on the trunk and extremities. Histopathology of the skin biopsy demonstrated subepidermal bullae and lymphocytic infiltration with eosinophils in the dermis. Direct immunofluorescence revealed linear deposits of immunoglobulin (Ig)G, IgA and C3 along the basement membrane zone. Indirect immunofluorescence of 1 mol/L NaCl-split skin showed IgG reactivity with both epidermal and the dermal sides. IgM reactivity with both the epidermal and dermal sides was also detected. Enzyme-linked immunosorbent assays showed negative results for both BP180 and BP230. Immunoelectrophoresis of serum and bone marrow aspiration revealed underlying primary macroglobulinemia with M-proteinemia of IgM-κ type. Immunoblot analysis revealed IgG, but not IgM, antibodies to recombinant protein of BP180 C-terminal domain. We diagnosed the present case as bullous pemphigoid with IgG anti-BP180 C-terminal domain autoantibodies associated with primary macroglobulinemia and psoriasis vulgaris. Systemic administration of prednisolone 30 mg/day resulted in dramatic improvement of both bullous and psoriatic skin lesions. When the bullous and psoriatic lesions relapsed, DRC chemotherapy (dexamethasone, rituximab and cyclophosphamide) for macroglobulinemia was performed. Then, the psoriatic lesions improved and the bullous lesions disappeared. We suggested that the present case may be paraneoplastic syndrome of bullous pemphigoid associated with primary macroglobulinemia and psoriasis vulgaris. PMID:26507447

  2. Anti-Inflammatory Action of Keratinocyte-Derived Vaspin: Relevance for the Pathogenesis of Psoriasis.

    PubMed

    Saalbach, Anja; Tremel, Jenny; Herbert, Diana; Schwede, Katharina; Wandel, Elke; Schirmer, Christine; Anderegg, Ulf; Beck-Sickinger, Annette G; Heiker, John T; Schultz, Stephan; Magin, Thomas; Simon, Jan C

    2016-03-01

    Impaired cross talk between keratinocytes (KCs) and immune cells is believed to contribute to the pathogenesis of chronic inflammatory skin diseases, such as psoriasis. We have previously identified KCs as a rich source of the serpin protease inhibitor vaspin (serpinA12), originally described as an adipokine in adipose tissue. Herein, we studied whether dysregulated vaspin expression in KCs contributes to the pathogenesis of psoriasis. We found vaspin expression to be closely associated to epidermal differentiation, with low levels in proliferating KCs and high levels in differentiated cells. Consistently, in human psoriasis and in a mouse model of a psoriasis-like skin inflammation, epidermal vaspin expression was significantly down-regulated. Down-regulation of vaspin in KCs resulted in decreased expression of differentiation-associated genes and up-regulation of interferon-inducible and inflammation-associated psoriasis signature genes. Vaspin was also shown to modulate the communication between KCs and inflammatory cells under co-culture conditions. A decrease in vaspin expression in KCs stimulated the secretion of tumor necrosis factor-α, IL-1β, IL-6, IL-8, and monocyte chemoattractant protein-1 by co-cultured dendritic cells, macrophages, monocytes, and neutrophils. Consequently, the application of vaspin inhibited myeloid cell infiltration in a mouse model of a psoriasis-like skin inflammation. In conclusion, vaspin expression by maturing KCs modulates cutaneous immune responses and may be involved in the pathogenesis of psoriasis. PMID:26783881

  3. Combination therapy using maxacalcitol and corticosteroid lotions preliminary to monotherapy with maxacalcitol lotion for scalp psoriasis.

    PubMed

    Okubo, Yukari; Natsume, Shoko; Usui, Kae; Muro, Mayuko; Tsuboi, Ryoji

    2014-02-01

    Topical treatment with betamethasone butyrate propionate lotion on 37 patients with scalp psoriasis was replaced with a combination therapy using maxacalcitol lotion (on weekdays) and BBP (on the weekends). This combination therapy was later switched to MXA monotherapy. To identify the optimum duration of the combination therapy, the patients were divided into two groups: a 4-week group and an 8-week group, which were given combination therapy and monotherapy. In both groups, the total mean scores for the skin symptoms had significantly improved in comparison with that obtained at the outset of the study (p < 0.01). In terms of overall improvement, 20.0% of the 4-week group and 72.7% of the 8-week group yielded scores reflecting moderate or greater improvement. The treatment administered to the 8-week group was significantly more effective than that given to the 4-week group at the end of the trial (p < 0.01). This study also suggests that a 4-week combination therapy is an option before switching to monotherapy, but that an 8-week therapy is preferable in severe cases. PMID:22515652

  4. Long term efficacy and safety of etanercept in the treatment of psoriasis and psoriatic arthritis

    PubMed Central

    Kivelevitch, Dario; Mansouri, Bobbak; Menter, Alan

    2014-01-01

    Psoriasis is a chronic, immune-mediated inflammatory disease affecting both the skin and joints. Approximately 20% of patients suffer a moderate to severe form of skin disease and up to 30% have joint involvement. Standard therapies for psoriasis include topical medications, phototherapy, and both oral systemic and biological therapies whereas therapies for psoriatic arthritis include nonsteroidal anti-inflammatory drugs followed by disease modifying antirheumatic drugs and/or tumor necrosis factor (TNF)-α inhibitors and interleukin-12/23p40 inhibitors. Treatment of both diseases is typically driven by disease severity. In the past decade, major advances in the understanding of the immunopathogenesis of psoriasis and psoriatic arthritis have led to the development of numerous biological therapies, which have revolutionized the treatment for moderate to severe plaque psoriasis and psoriatic arthritis. Anti-TNF-α agents are currently considered as first line biological therapies for the treatment of moderate to severe psoriasis and psoriatic arthritis. Currently approved anti-TNF-α agents include etanercept, adalimumab, and infliximab for psoriasis and psoriatic arthritis as well as golimumab and certolizumab for psoriatic arthritis. In this article, we aim to evaluate the long term safety and efficacy of etanercept in psoriasis and psoriatic arthritis. PMID:24790410

  5. [Combined topical therapy of psoriasis: position of calcitriol and vitamin D analogs].

    PubMed

    Schmitt, J; Meurer, M

    2006-08-01

    Most patients with mild to moderate psoriasis require--often longterm--topical treatments: this frequently results in non-compliance especially when large body areas or the face are treated. Monotherapy with anthralin has been abandoned to a great extent while new formulations of topical corticosteroids, vitamin D and vitamin D derivatives have greatly extended the spectrum of topical antipsoriatic treatment modalities. In most instances, combinations of preparations with different pharmacologic modes of action are superior when compared with the respective monotherapy. This also holds true for combinations with a UVB or UVA light therapy. Preparations containing both a corticosteroid and vitamin D derivative are well suited for combining topical treatment with modern systemic antipsoriatic drugs. PMID:16865352

  6. Assessing disease activity in psoriasis and psoriatic arthritis: impact on management and therapy.

    PubMed

    Chandran, Vinod; Maharaj, Ajesh B

    2016-05-01

    The management of psoriatic arthritis (PsA) and psoriasis has undergone major advancements over the last decade. This has been made possible, in part, due to the introduction of new therapies for their management, as well as global collaboration in the development of outcome measures and "treat- to- target" paradigms. In this review article, we discuss how disease activity is measured and the outcome measures that have been recently developed for the management of PsA. The importance of assessing the individual domains as well as global assessments both from the physician and patient perspective, and the development of composite measures are discussed. The newer PsA specific measures are expected to be more commonly used in clinical trials as well as clinical practice. PMID:26807494

  7. Capsaicin-loaded vesicular systems designed for enhancing localized delivery for psoriasis therapy.

    PubMed

    Gupta, Ruchi; Gupta, Madhu; Mangal, Sharad; Agrawal, Udita; Vyas, Suresh Prasad

    2016-05-01

    The aim of the current investigation is to evaluate the potential of capsaicin (CAP)-containing liposomes, niosomes and emulsomes in providing localized and controlled delivery, to improve the topical delivery of drug. CAP-bearing systems were prepared by the film hydration method and compared through various in vitro and in vivo parameters. The TEM photographs suggested that the carrier systems were spherical in shape and nanometric in size range. Skin retention studies of CAP from in vitro and in vivo experiments revealed significantly higher accumulation of drug in the case of the emul-gel formulation. Based on the results, we concluded that the emul-gel may be a potential approach for the topical delivery of CAP, for an effective therapy for psoriasis. PMID:25465045

  8. A case of multiple bone fractures due to the use of topical corticosteroid therapy for psoriasis.

    PubMed

    Gönül, Müzeyyen; Gönül, Engin

    2015-06-01

    A 45-year-old man who had psoriasis had applied topical clobetasol 17 propionate ointment on his whole body 2-3 times a week after the bath for 20 years. Physical examination showed abdominal distension, atrophy all over the skin, psoriatic plaques on the trunk, and extremities and multiple striae on the shoulders and legs. Morning plasma cortisol level and ACTH stimulation test confirmed the diagnosis of hypothalamic insufficiency. Bone mineral densitometry showed severe osteoporosis. Multiple bone fractures in the vertebrae and costa were detected on lumbar magnetic resonance imaging, the (99)Tc MDP whole-body bone scan, and thoracoabdominal computerized tomography imaging. Topical corticosteroid therapies have possible local and/or systemic side effects such as atrophy, telangiectasia, hypertricosis, and suppression of pituitary-adrenal axis. We present an interesting case with multiple bone fractures caused by long-time topical corticosteroid use. PMID:24913132

  9. Vascular endothelial growth factor inhibitors: investigational therapies for the treatment of psoriasis

    PubMed Central

    Weidemann, Anja K; Crawshaw, Ania A; Byrne, Emily; Young, Helen S

    2013-01-01

    Psoriasis is a common inflammatory autoimmune condition in which environmental factors and genetic predisposition contribute to the development of disease in susceptible individuals. Angiogenesis is known to be a key pathogenic feature of psoriasis. Local and systemic elevation of vascular endothelial growth factor (VEGF)-A has been demonstrated in the skin and plasma of patients with psoriasis and is known to correlate with improvement following some traditional psoriasis treatments. A number of VEGF inhibitors are licensed for the treatment of malignancies and eye disease and isolated case reports suggest that some individuals with psoriasis may improve when exposed to these agents. The small number of cases and lack of unified reporting measures makes it difficult to draw generalizations and underline the heterogeneity of psoriasis as a disease entity. Though not yet licensed for the treatment of psoriasis in humans, experimental data supports the potential of VEGF inhibitors to influence relevant aspects of human cell biology (such as endothelial cell differentiation) and to improve animal models of skin disease. Given the multi-factorial nature of psoriasis it is unlikely that VEGF inhibitors will be effective in all patients, however they have the potential to be a valuable addition to the therapeutic arsenal in selected cases. Current VEGF inhibitors in clinical use are associated with a number of potentially serious side effects including hypertension, left ventricular dysfunction, and gastrointestinal perforation. Such risks require careful consideration in psoriasis populations particularly in light of growing concerns linking psoriasis to increased cardiovascular risk. PMID:24101875

  10. Vascular endothelial growth factor inhibitors: investigational therapies for the treatment of psoriasis.

    PubMed

    Weidemann, Anja K; Crawshaw, Ania A; Byrne, Emily; Young, Helen S

    2013-01-01

    Psoriasis is a common inflammatory autoimmune condition in which environmental factors and genetic predisposition contribute to the development of disease in susceptible individuals. Angiogenesis is known to be a key pathogenic feature of psoriasis. Local and systemic elevation of vascular endothelial growth factor (VEGF)-A has been demonstrated in the skin and plasma of patients with psoriasis and is known to correlate with improvement following some traditional psoriasis treatments. A number of VEGF inhibitors are licensed for the treatment of malignancies and eye disease and isolated case reports suggest that some individuals with psoriasis may improve when exposed to these agents. The small number of cases and lack of unified reporting measures makes it difficult to draw generalizations and underline the heterogeneity of psoriasis as a disease entity. Though not yet licensed for the treatment of psoriasis in humans, experimental data supports the potential of VEGF inhibitors to influence relevant aspects of human cell biology (such as endothelial cell differentiation) and to improve animal models of skin disease. Given the multi-factorial nature of psoriasis it is unlikely that VEGF inhibitors will be effective in all patients, however they have the potential to be a valuable addition to the therapeutic arsenal in selected cases. Current VEGF inhibitors in clinical use are associated with a number of potentially serious side effects including hypertension, left ventricular dysfunction, and gastrointestinal perforation. Such risks require careful consideration in psoriasis populations particularly in light of growing concerns linking psoriasis to increased cardiovascular risk. PMID:24101875

  11. Isoniazid toxicity and TB development during biological therapy of patients with psoriasis in Colombia.

    PubMed

    Cataño, Juan; Morales, Milena

    2016-10-01

    Background The use of biological therapy has been linked with an increased risk of tuberculosis (TB) reactivation. Objective The aim of this study was to present the follow-up results for Isoniazid (INH) chemoprophylaxis in patients with psoriasis receiving different biological therapies. Methods In this prospective observational study, patients with latent tuberculosis infection (LTBI) were given INH chemoprophylaxis between two and nine months prior to the beginning of biological therapy. All patients were followed up monthly for any signs or symptoms of active TB or INH toxicity. Results A total of 101 patients, 44.5% females, with a mean age of 46.9 ± 11.5 years (20-73) were enrolled. LTBI was identified in 100 patients (99%), of whom 81.2% completed nine months of chemoprophylaxis. Three patients (2.9%) developed active TB and 17 patients (16.8%) developed intolerance or toxicity related to INH. Conclusions Chemoprophylaxis with INH seems to be effective and safe for the prevention of most TB reactivations in individuals with LTBI receiving biological therapy, but toxicity must be monitored during follow-up. PMID:27003177

  12. Exploring the mode of action of dithranol therapy for psoriasis: a metabolomic analysis using HaCaT cells.

    PubMed

    Hollywood, Katherine A; Winder, Catherine L; Dunn, Warwick B; Xu, Yun; Broadhurst, David; Griffiths, Christopher E M; Goodacre, Royston

    2015-08-01

    Psoriasis is a common, immune-mediated inflammatory skin disease characterized by red, heavily scaled plaques. The disease affects over one million people in the UK and causes significant physical, psychological and societal impact. There is limited understanding regarding the exact pathogenesis of the disease although it is believed to be a consequence of genetic predisposition and environmental triggers. Treatments vary from topical therapies, such as dithranol, for disease of limited extent (<5% body surface area) to the new immune-targeted biologic therapies for severe psoriasis. Dithranol (also known as anthralin) is a topical therapy for psoriasis believed to work by inhibiting keratinocyte proliferation. To date there have been no metabolomic-based investigations into psoriasis. The HaCaT cell line is a model system for the epidermal keratinocyte proliferation characteristic of psoriasis and was thus chosen for study. Dithranol was applied at therapeutically relevant doses to HaCaT cells. Following the optimisation of enzyme inactivation and metabolite extraction, gas chromatography-mass spectrometry was employed for metabolomics as this addresses central metabolism. Cells were challenged with 0-0.5 μg mL(-1) in 0.1 μg mL(-1) steps and this quantitative perturbation generated data that were highly amenable to correlation analysis. Thus, we used a combination of traditional principal components analysis, hierarchical cluster analysis, along with correlation networks. All methods highlighted distinct metabolite groups, which had different metabolite trajectories with respect to drug concentration and the interpretation of these data established that cellular metabolism had been altered significantly and provided further clarification of the proposed mechanism of action of the drug. PMID:26018604

  13. Psoriasis: Behind the scenes.

    PubMed

    Furue, Masutaka; Kadono, Takafumi

    2016-01-01

    Psoriasis is a chronic inflammatory skin disease characterized by a significant deterioration in the quality of life of affected individuals. Notably, psoriasis is significantly associated with cardiovascular and metabolic syndrome and other autoimmune disorders. Recent progress in biologic therapies has revealed the fundamental role of tumor necrosis factor-α, interleukin (IL)-23 and the IL-17A axis together with aberrant overproduction of epidermal IL-36γ in the pathogenesis of psoriasis. This review provides an update on the clinical, pathological and therapeutic advancements involving psoriasis. PMID:26782000

  14. Psoriasis: the future.

    PubMed

    Menter, M Alan; Griffiths, Christopher E M

    2015-01-01

    The umbrella term psoriasis is now understood to incorporate several distinct phenotypes or endotypes along the disease spectrum that in turn will dictate different therapies. A stratified medicine approach to psoriasis using this clinical information coupled with pharmacogenomic and immunologic data will become more widely acceptable in the future. Comorbidities associated with psoriasis, such as diabetes, depression, and Crohn disease, and the debate about the interdependence of psoriasis and cardiovascular disease will also dictate future research and holistic and management plans for this complex disease. PMID:25412790

  15. Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control

    PubMed Central

    Lee, Young-Sun; Jun, Hee-Sook

    2016-01-01

    Glucagon-like peptide-1 (GLP-1) is an incretin hormone mainly secreted from intestinal L cells in response to nutrient ingestion. GLP-1 has beneficial effects for glucose homeostasis by stimulating insulin secretion from pancreatic beta-cells, delaying gastric emptying, decreasing plasma glucagon, reducing food intake, and stimulating glucose disposal. Therefore, GLP-1-based therapies such as GLP-1 receptor agonists and inhibitors of dipeptidyl peptidase-4, which is a GLP-1 inactivating enzyme, have been developed for treatment of type 2 diabetes. In addition to glucose-lowering effects, emerging data suggests that GLP-1-based therapies also show anti-inflammatory effects in chronic inflammatory diseases including type 1 and 2 diabetes, atherosclerosis, neurodegenerative disorders, nonalcoholic steatohepatitis, diabetic nephropathy, asthma, and psoriasis. This review outlines the anti-inflammatory actions of GLP-1-based therapies on diseases associated with chronic inflammation in vivo and in vitro, and their molecular mechanisms of anti-inflammatory action. PMID:27110066

  16. Association of Trabecular Bone Score with Inflammation and Adiposity in Patients with Psoriasis: Effect of Adalimumab Therapy.

    PubMed

    Hernández, José L; López-Mejías, Raquel; Blanco, Ricardo; Pina, Trinitario; Ruiz, Sheila; Sierra, Isabel; Ubilla, Begoña; Mijares, Verónica; González-López, Marcos A; Armesto, Susana; Corrales, Alfonso; Pons, Enar; Fuentevilla, Patricia; González-Vela, Carmen; González-Gay, Miguel Á

    2016-01-01

    Studies on trabecular bone score (TBS) in psoriasis are lacking. We aim to assess the association between TBS and inflammation, metabolic syndrome features, and serum adipokines in 29 nondiabetic patients with psoriasis without arthritis, before and after 6-month adalimumab therapy. For that purpose, adjusted partial correlations and stepwise multivariable linear regression analysis were performed. No correlation was found between TBS and disease severity. TBS was negatively associated with weight, BMI, waist perimeter, fat percentage, and systolic and diastolic blood pressure before and after adalimumab. After 6 months of therapy, a negative correlation between TBS and insulin resistance (p = 0.02) and leptin (p = 0.01) and a positive correlation with adiponectin were found (p = 0.01). The best set of predictors for TBS values at baseline were female sex (p = 0.015), age (p = 0.05), and BMI (p = 0.001). The best set of predictors for TBS following 6 months of biologic therapy were age (p = 0.001), BMI (p < 0.0001), and serum adiponectin levels (p = 0.027). In conclusion, in nondiabetic patients with moderate-to-severe psoriasis, TBS correlates with metabolic syndrome features and inflammation. This association is still present after 6 months of adalimumab therapy. Moreover, serum adiponectin levels seem to be an independent variable related to TBS values, after adalimumab therapy. PMID:27293954

  17. Association of Trabecular Bone Score with Inflammation and Adiposity in Patients with Psoriasis: Effect of Adalimumab Therapy

    PubMed Central

    Hernández, José L.; López-Mejías, Raquel; Blanco, Ricardo; Pina, Trinitario; Ruiz, Sheila; Sierra, Isabel; Ubilla, Begoña; Mijares, Verónica; González-López, Marcos A.; Armesto, Susana; Corrales, Alfonso; Pons, Enar; Fuentevilla, Patricia; González-Vela, Carmen; González-Gay, Miguel Á.

    2016-01-01

    Studies on trabecular bone score (TBS) in psoriasis are lacking. We aim to assess the association between TBS and inflammation, metabolic syndrome features, and serum adipokines in 29 nondiabetic patients with psoriasis without arthritis, before and after 6-month adalimumab therapy. For that purpose, adjusted partial correlations and stepwise multivariable linear regression analysis were performed. No correlation was found between TBS and disease severity. TBS was negatively associated with weight, BMI, waist perimeter, fat percentage, and systolic and diastolic blood pressure before and after adalimumab. After 6 months of therapy, a negative correlation between TBS and insulin resistance (p = 0.02) and leptin (p = 0.01) and a positive correlation with adiponectin were found (p = 0.01). The best set of predictors for TBS values at baseline were female sex (p = 0.015), age (p = 0.05), and BMI (p = 0.001). The best set of predictors for TBS following 6 months of biologic therapy were age (p = 0.001), BMI (p < 0.0001), and serum adiponectin levels (p = 0.027). In conclusion, in nondiabetic patients with moderate-to-severe psoriasis, TBS correlates with metabolic syndrome features and inflammation. This association is still present after 6 months of adalimumab therapy. Moreover, serum adiponectin levels seem to be an independent variable related to TBS values, after adalimumab therapy. PMID:27293954

  18. [Psoriasis in special localizations].

    PubMed

    Schmieder, A; Peitsch, W K

    2016-06-01

    A large proportion of patients with plaque psoriasis suffer from psoriatic lesions of the scalp, nails, and intertrigines. These locations can also be soley or predominantly affected. Scalp psoriasis, nail psoriasis, and inverse psoriasis are often perceived as particularly stigmatizing. Involvement of these parts of the body is associated with an increased risk of psoriatic arthritis. Location-specific features must be considered when choosing treatment. Evidence for topical therapy of scalp psoriasis with steroids and combinations of steroids and vitamin D analogues is high. These agents are regarded as safe and effective treatments of first choice. Efficacy of TNF antagonists and apremilast is well documented for refractory scalp psoriasis. Nail psoriasis often responds insufficiently to topical therapy. Several effective systemic medications including methotrexate and TNF antagonists are available for treatment of severe forms. Controlled trials for treatment of inverse psoriasis are scarce. Topical steroids, vitamin D analogues, dithranol, and off-label calcineurin inhibitors are used in clinical practice. This review provides a survey on the clinical presentation and current evidence for treatment of psoriasis in challenging locations. PMID:27215754

  19. Potential role of ixekizumab in the treatment of moderate-to-severe plaque psoriasis

    PubMed Central

    Ren, Vicky; Dao, Harry

    2013-01-01

    Background Psoriasis is a debilitating autoimmune skin disease that affects 2%–3% of the world’s population. Patients with moderate-to-severe plaque psoriasis suffer from a decreased quality of life as well as comorbidities. Newer biological agents have been shown to be more effective than traditional therapies. In this article, we assess the potential role of ixekizumab, an anti-interleukin (IL)-17 antibody, in treating moderate-to-severe plaque psoriasis. Method We reviewed PubMed for articles regarding ixekizumab and the epidemiology and management of plaque psoriasis. Results In a Phase I clinical trial, treatment with ixekizumab resulted in both clinical and histopathologic improvement of psoriasis, which suggests that IL-17 may be a key driver in the pathogenesis of psoriasis. In a Phase II clinical trial, treatment with ixekizumab resulted in rapid clinical improvement of psoriasis, which lends further support to its role as an effective treatment for patients with chronic moderate-to-severe plaque psoriasis. Reductions in Psoriasis Area and Severity Index (PASI) score are comparable to those associated with currently marketed biologics. Conclusion Literature concerning the effects of ixekizumab on chronic moderate-to-severe plaque psoriasis is currently limited to two clinical trials. Results suggest that ixekizumab shows great therapeutic promise. However, more large-scale and long-term trials are needed to establish safety and efficacy. PMID:23515267

  20. Psoriasis - resources

    MedlinePlus

    Resources - psoriasis ... The following organizations are good resources for information about psoriasis : American Academy of Dermatology -- www.aad.org/skin-conditions/dermatology-a-to-z/psoriasis National Institute of ...

  1. Palmoplantar pustular psoriasis induced by adalimumab: a case report and literature review.

    PubMed

    Ibis, Nurdan; Hocaoglu, Sehriban; Cebicci, Mehtap Aykac; Sutbeyaz, Serap Tomruk; Calis, Havva Talay

    2015-01-01

    TNF-α inhibitors (anti-TNF-α) are agents increasingly used in the treatment of rheumatic diseases resistant to classical disease-modifying treatment and they provide significant improvement of disease activity. However, these agents have many cutaneous side effects including psoriasis. Numerous reports of the induction or worsening of psoriasis in patients treated with TNF antagonists indicate that this is not a rare phenomenon. In this study, we present a patient with ankylosing spondylitis who developed palmoplantar pustular psoriasis after receiving anti-TNF-α therapy for 4 months. PMID:26250408

  2. Therapy of psoriasis in childhood and adolescence - a German expert consensus.

    PubMed

    Sticherling, Michael; Augustin, Matthias; Boehncke, Wolf-Henning; Christophers, Enno; Domm, Silja; Gollnick, Harald; Reich, Kristian; Mrowietz, Ulrich

    2011-10-01

    Psoriasis of childhood shows an annual prevalence of 0.71 % and accordingly has to be regarded as a frequent chronic inflammatory skin disorder of this age. The impact on the quality of life as well as development of the afflicted children and their parents is evident. On the other side, therapy is demanding with regard to the specific juvenile metabolism, physical development and skin penetration of topical drugs. Long-term treatment at an early age has to be critically judged regarding the chronicity of the disease. Topical corticosteroids, alternatively dithranol may be used first-line, followed by vitamin D derivatives. A combination with UV-light, preferably UV-B, has to be decided on an individual basis. Systemic treatment may be initiated in recalcitrant disease with methotrexate and cyclosporine where long-term experience is available from juvenile rheumatology and transplantation medicine. Alternatively fumaric acid esters or retinoids are available. Rehabilitation procedures will help the children and their parents to cope with the disease and its treatment. The different treatment options are presented here as a German expert consensus, as clinical studies are hardly available and only a few therapeutics are licensed for this age. In any case the therapy has to be individually planned and decided together with the patients and their parents to gain maximal safety, comfort and success. PMID:21585653

  3. Pharmacogenomics of Anti-platelet and Anti-coagulation Therapy

    PubMed Central

    Fisch, Adam S.; Perry, Christina G.; Stephens, Sarah H.; Horenstein, Richard B.; Shuldiner, Alan R.

    2013-01-01

    Arterial thrombosis is a major component of vascular disease, especially myocardial infarction (MI) and stroke. Current anti-thrombotic therapies such as warfarin and clopidogrel are effective in inhibiting cardiovascular events; however, there is great inter-individual variability in response to these medications. In recent years, it has been recognized that genetic factors play a significant role in drug response, and, subsequently, common variants in genes responsible for metabolism and drug action have been identified. These discoveries along with the new diagnostic targets and therapeutic strategies on the horizon hold promise for more effective individualized anti-coagulation and anti-platelet therapy. PMID:23797323

  4. The anti-inflammatory target A(3) adenosine receptor is over-expressed in rheumatoid arthritis, psoriasis and Crohn's disease.

    PubMed

    Ochaion, A; Bar-Yehuda, S; Cohen, S; Barer, F; Patoka, R; Amital, H; Reitblat, T; Reitblat, A; Ophir, J; Konfino, I; Chowers, Y; Ben-Horin, S; Fishman, P

    2009-01-01

    The Gi protein associated A(3) adenosine receptor (A(3)AR) was recently defined as a novel anti-inflammatory target. The aim of this study was to look at A(3)AR expression levels in peripheral blood mononuclear cells (PBMCs) of patients with autoimmune inflammatory diseases and to explore transcription factors involved receptor expression. Over-expression of A(3)AR was found in PBMCs derived from patients with rheumatoid arthritis (RA), psoriasis and Crohn's disease compared with PBMCs from healthy subjects. Bioinformatics analysis demonstrated the presence of DNA binding sites for nuclear factor-kappaB (NF-kappaB) and cyclic AMP-responsive element binding protein (CREB) in the A(3)AR gene promoter. Up-regulation of NF-kappaB and CREB was found in the PBMCs from patients with RA, psoriasis and Crohn's disease. The PI3K-PKB/Akt signaling pathway, known to regulate both the NF-kappaB and CREB, was also up-regulated in the patients' PBMCs. Taken together, NF-kappaB and CREB are involved with the over-expression of A(3)AR in patients with autoimmune inflammatory diseases. The receptor may be considered as a specific target to combat inflammation. PMID:19426966

  5. IL-17 in psoriasis: Implications for therapy and cardiovascular co-morbidities

    PubMed Central

    Golden, Jackelyn B.; McCormick, Thomas S.; Ward, Nicole L.

    2013-01-01

    Psoriasis is a prevalent, chronic inflammatory disease of the skin mediated by cross-talk occurring between epidermal keratinocytes, dermal vascular cells and immunocytes, including activated antigen presenting cells (APCs), monocytes/macrophages, and Th1 and Th17 cells. Increased proliferation of keratinocytes and endothelial cells in conjunction with immune cell infiltration leads to the distinct epidermal and vascular hyperplasia that is characteristic of lesional psoriatic skin. Interaction of activated T cells with monocytes/macrophages occurs via the Th17/IL-23 axis and is crucial for maintaining the chronic inflammation. Recent epidemiological evidence has demonstrated that psoriasis patients have an increased risk of developing and dying of cardiovascular disease. Similar pathology between psoriasis and cardiovascular disease, including involvement of key immunologic cell populations together with release of common inflammatory mediators such as IL-17A suggest a mechanistic link between the two diseases. This review will focus on concepts critical to psoriasis pathogenesis, systemic manifestations of psoriasis, the role of IL-17 in psoriasis and cardiovascular disease and the potential role for IL-17 in mediating cardiovascular co-morbidities in psoriasis patients. PMID:23562549

  6. Treatment of psoriasis and psoriatic arthritis during pregnancy and breastfeeding*

    PubMed Central

    Kurizky, Patricia Shu; Ferreira, Clarissa de Castro; Nogueira, Lucas Souza Carmo; da Mota, Licia Maria Henrique

    2015-01-01

    Psoriasis is a chronic inflammatory disease that affects primarily the skin and joints, with a worldwide incidence of 2-3%. Fifty percent of patients are women, most still diagnosed during childbearing years. Currently,the estimate is that up to 107 thousand deliveries are performed annually in women with psoriasis, a percentage of them in women with moderate to severe disease. Fetal risks in pregnant women with psoriasis derive both from maternal disease and the medications used to control the illness. The purpose of this review is to study the effect of the main drugs used in the treatment of psoriasis and psoriatic arthritis during pregnancy and lactation, with particular focus on disease-modifying anti-rheumatic biological drugs, biological therapies, immunobiologics or biologics. PMID:26131868

  7. Treatment of psoriasis and psoriatic arthritis during pregnancy and breastfeeding.

    PubMed

    Kurizky, Patricia Shu; Ferreira, Clarissa de Castro; Nogueira, Lucas Souza Carmo; Mota, Licia Maria Henrique da

    2015-01-01

    Psoriasis is a chronic inflammatory disease that affects primarily the skin and joints, with a worldwide incidence of 2-3%. Fifty percent of patients are women, most still diagnosed during childbearing years. Currently,the estimate is that up to 107 thousand deliveries are performed annually in women with psoriasis, a percentage of them in women with moderate to severe disease. Fetal risks in pregnant women with psoriasis derive both from maternal disease and the medications used to control the illness. The purpose of this review is to study the effect of the main drugs used in the treatment of psoriasis and psoriatic arthritis during pregnancy and lactation, with particular focus on disease-modifying anti-rheumatic biological drugs, biological therapies, immunobiologics or biologics. PMID:26131868

  8. Palmoplantar Psoriasis and Palmoplantar Pustulosis: Current Treatment and Future Prospects.

    PubMed

    Raposo, Inês; Torres, Tiago

    2016-08-01

    Palmoplantar psoriasis and palmoplantar pustulosis are chronic skin diseases with a large impact on patient quality of life. They are frequently refractory to treatment, being generally described as a therapeutic challenge. This article aims to review the definitions of palmoplantar psoriasis and palmoplantar pustulosis, highlighting the similarities and differences in terms of epidemiology, clinical presentation, genetics, histopathology, and pathogenesis, as well as treatment options for both entities. Classical management of mild to moderate palmoplantar pustulosis and palmoplantar psoriasis relies on use of potent topical corticosteroids, phototherapy, and/or acitretin. Nevertheless, these drugs have proven to be insufficient in long-term control of extensive disease. Biologic therapy-namely, anti-interleukin-17 agents and phosphodiesterase type 4 inhibitors-has recently shown promising results in the treatment of palmoplantar psoriasis. Knowledge of the pathophysiologic pathways of both entities is of utmost importance and may, in the future, allow development of molecularly targeted therapeutics. PMID:27113059

  9. Risk of Serious Infections in Patients with Psoriasis on Biologic Therapies: A Systematic Review and Meta-Analysis.

    PubMed

    Yiu, Zenas Z N; Exton, Lesley S; Jabbar-Lopez, Zarif; Mohd Mustapa, M Firouz; Samarasekera, Eleanor J; Burden, A David; Murphy, Ruth; Owen, Caroline M; Parslew, Richard; Venning, Vanessa; Ashcroft, Darren M; Griffiths, Christopher E M; Smith, Catherine H; Warren, Richard B

    2016-08-01

    A comprehensive evaluation of the risk of serious infections in biologic therapies for psoriasis is lacking. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) and prospective cohort studies reporting serious infections in people taking any licensed biologic therapy for psoriasis compared with those taking placebo, nonbiologic therapy, or other biologic therapies. The quality of the studies was assessed using Grading of Recommendations Assessment, Development and Evaluation criteria. No significant heterogeneity was detected in data from 32 RCTs (n = 13,359 participants) and one cohort study (n = 4,993 participants). In adults, low- to very-low-quality RCT data showed no significant difference between any biologic therapy and placebo at weeks 12-16 (overall pooled Peto odds ratio = 0.71, 95% confidence interval = 0.36-1.41) and weeks 20-30 (odds ratio = 2.27, 95% confidence interval = 0.45-11.49). No significant differences were found in any of the other comparisons in underpowered RCT data. Prospective cohort study data of low quality suggests that only adalimumab (adjusted hazard ratio [adjHR] = 2.52, 95% confidence interval = 1.47-4.32) was associated with a significantly higher risk of serious infection compared with retinoid and/or phototherapy in adults. No association between biologic therapies and serious infections in patients with psoriasis who were eligible for RCTs was detected. Further observational studies are needed to inform the uncertainty around this risk in the real world. PMID:27085754

  10. Use of aspirin, non-steroidal anti-inflammatory drugs, and acetaminophen (paracetamol), and risk of psoriasis and psoriatic arthritis: a cohort study.

    PubMed

    Wu, Shaowei; Han, Jiali; Qureshi, Abrar A

    2015-02-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to induce or exacerbate psoriasis. We aimed to evaluate the association between several widely used analgesics, including aspirin, non-aspirin NSAIDs, and acetaminophen (paracetamol), and risk of psoriasis and psoriatic arthritis (PsA) in a large cohort of US women, the Nurses' Health Study II (1991-2005). Information on regular use of aspirin, NSAIDs, and acetaminophen was collected for 95,540 participants during the follow-up. During 1,321,280 person-years of follow-up, we documented 646 incident psoriasis cases and 165 concomitant PsA cases. Compared to women who reported no use, regular acetaminophen and NSAIDs users with more than 10 years of use had multivariate hazard ratios of 3.60 [95% confidence interval (CI): 2.02-6.41] and 2.10 (95% CI: 1.11-3.96) for PsA, respectively. There was no clear association between aspirin and risk of psoriasis or PsA. In conclusion, long-term acetaminophen and NSAIDs use may be associated with an increased risk of PsA. Special attention on psoriasis and PsA screening may be needed for those who are prescribed for acetaminophen and NSAIDs for long-term periods. PMID:24691893

  11. Use of Aspirin, Nonsteroidal Anti-inflammatory Drugs, and Acetaminophen (Paracetamol), and Risk of Psoriasis and Psoriatic Arthritis: A Cohort Study

    PubMed Central

    Wu, Shaowei; Han, Jiali; Qureshi, Abrar A.

    2014-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to induce or exacerbate psoriasis. We aimed to evaluate the association between several widely used analgesics, including aspirin, nonaspirin NSAIDs, and acetaminophen (paracetamol), and risk of psoriasis and psoriatic arthritis (PsA) in a large cohort of US women (1991–2005). Information on regular use of aspirin, NSAIDs, and acetaminophen was collected for 95 540 participants during the follow-up. During 1 321 280 person-years of follow-up, we documented 646 incident psoriasis cases and 165 concomitant PsA cases. Compared to women who reported no use, regular acetaminophen and NSAIDs users with more than 10 years of use had multivariate hazard ratios (HRs) of 3.60 [95% confidence interval (CI): 2.02–6.41] and 2.10 (95% CI: 1.11–3.96) respectively for PsA. There was no clear association between aspirin and risk of psoriasis or PsA. In conclusion, long-term acetaminophen and NSAIDs use may be associated with an increased risk of PsA. Special attention on psoriasis and PsA screening may be needed for those who are prescribed for acetaminophen and NSAIDs. PMID:24691893

  12. Pediatric psoriasis: an update

    PubMed Central

    Silverberg, Nanette B

    2009-01-01

    Pediatric psoriasis consists broadly of 3 age groups of psoriatic patients: infantile psoriasis, a self-limited disease of infancy, psoriasis with early onset, and pediatric psoriasis with psoriatic arthritis. About one-quarter of psoriasis cases begin before the age of 18 years. A variety of clinical psoriasis types are seen in childhood, including plaque-type, guttate, erythrodermic, napkin, and nail-based disease. Like all forms of auto-immunity, susceptibility is likely genetic, but environmental triggers are required to initiate disease activity. The most common trigger of childhood is an upper respiratory tract infection. Once disease has occurred, treatment is determined based on severity and presence of joint involvement. Topical therapies, including corticosteroids and calcipotriene, are the therapies of choice in the initial care of pediatric patients. Ultraviolet light, acitretin and cyclosporine can clear skin symptoms, while methotrexate and etanercept can clear both cutaneous and joint disease. Concern for psychological development is required when choosing psoriatic therapies. This article reviews current concepts in pediatric psoriasis and a rational approach to therapeutics. PMID:19898649

  13. Anti cytokine therapy in chronic inflammatory arthritis.

    PubMed

    Thompson, Charlotte; Davies, Ruth; Choy, Ernest

    2016-10-01

    This is a review looking at anti cytokine therapy in Rheumatoid Arthritis (RA), Psoriatic Arthritis (PSA) and Ankylosing Spondylitis (AS). The review explores the similarities and differences in the clinical features, as well as treatments and cytokines involved in the development and propagation of the disease. Particular attention is paid to TNFα inhibitors IL-1ra, IL-6 and JAK kinase Inhibitors, anti IL23 and IL-12 and the new developments with anti-IL-17. PMID:27497159

  14. Apremilast in the therapy of moderate-to-severe chronic plaque psoriasis

    PubMed Central

    Gisondi, Paolo; Girolomoni, Giampiero

    2016-01-01

    Chronic plaque psoriasis presents clinically as an inflammatory disease of the skin, which is often associated with comorbidities and responsible for a poor quality of life. It can widely vary among patients because of different age of onset, type of symptoms, areas of involvement, and disease severity. The choice of the treatment of psoriasis should be personalized according to the specific needs of the patients. Apremilast is a well-tolerated and effective phosphodiesterase type 4 inhibitor that is indicated for the treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis. In this article, the pharmacological, clinical, and safety aspects of apremilast are reviewed. Based on these data, apremilast could be indicated for patients with a Psoriasis Area and Severity Index score <10 but with a significant impact on quality of life and seems to be an appropriate treatment for elderly patients also. PMID:27307707

  15. Current and potential immune therapies and vaccines in the management of psoriasis

    PubMed Central

    Kaffenberger, Benjamin H; Lee, Grace L; Tyler, Kelly; Chan, Derek V; Jarjour, Wael; Ariza, Maria E; Williams, Marshall V; Wong, Henry K

    2014-01-01

    Psoriasis is a chronic, immune skin disease associated with significant morbidity. Development of psoriasis is influenced by numerous genes, one allele is HLA-CW*0602. Other genes and single nucleotide polymorphisms affect immunologic pathways and antimicrobial peptide synthesis. Dendritic cells initiate psoriasis by activating T-cells toward a Th1 and Th17 response, with increased cytokines including TNF-α, IL-6, -12, -17, -22, and -23. IL-22 appears to promote keratinocyte dedifferentiation and increased antimicrobial peptide synthesis while TNF-α and IL-17 induce leukocyte localization within the psoriatic plaque. These recent insights identifying key cytokine pathways have led to the development of inhibitors with significant efficacy in the treatment of psoriasis. While a strategy for vaccine modulation of the immune response in psoriasis is in progress, with new technology they may provide a cost-effective long-term treatment that may induce tolerance or targeted self-inhibition for patients with autoimmune disorders, such as psoriasis. PMID:24492530

  16. TNF-α in a molecularly targeted therapy of psoriasis and psoriatic arthritis.

    PubMed

    Wcisło-Dziadecka, Dominika; Zbiciak-Nylec, Martyna; Brzezińska-Wcisło, Ligia; Mazurek, Urszula

    2016-03-01

    Psoriasis is a chronic immunological skin disease and patients with this disorder typically experience a significant decrease in their quality of life. The disease is traditionally managed with topical and systemic agents (retinoids, ciclosporin A, methotrexate), but these treatment options are often long-term and their effects can be inconsistent and not ideal. The use of biological drugs in dermatological treatment is relatively new and began in the early 2000s. It should be noted that, in most countries, in order for biological treatment to be administered, specific criteria must be met. The current treatment options for psoriasis and psoriatic arthritis include tumour necrosis factor alpha (TNF-α) blockers, interleukin (IL)-12 and IL-23 inhibitors, T cell inhibitors and B cell inhibitors. These classes of biological drugs are characterised by protein structure as well as high molecular weight and their effectiveness is evaluated based on the Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA) and the Dermatology Life Quality Index (DLQI). TNF-α antagonists are one such class of biological drugs which includes infliximad, etanercept and adalimumab. Infliximab is a chimeric protein that is administered via intravenous infusions as a monotherapy in psoriasis vulgaris. Etanercept is indicated for use in both psoriasis vulgaris and psoriatic arthritis and it is the only drug that can be used as a treatment for children under the age of 8 with psoriasis. The drug is administered subcutaneously. Finally, adalimumab is a fully human monoclonal antibody that neutralises both free and membrane-bound TNF-α and is used in the treatment of psoriasis vulgaris and psoriatic arthritis. This article reviews the latest research in the use of TNF-α for the treatment of moderate to severe psoriasis and psoriatic arthritis. The results of research in this field are promising and confirm the effectiveness and safety of biological drugs as dermatological treatments

  17. Anti-selectin therapy for the treatment of inflammatory diseases.

    PubMed

    Rossi, Barbara; Constantin, Gabriela

    2008-06-01

    Leukocyte migration into the tissues represents a key process in the pathogenesis of inflammatory diseases. Data obtained in clinical trials have convincingly shown that inhibition of leukocyte migration into the target organs represents an effective therapeutic approach for diseases in which inflammation has a noxious effect. Leukocyte tethering and rolling are the earliest steps of leukocyte adhesion cascade in inflamed vessels. Selectins are type I transmembrane glycoproteins that bind sialylated carbohydrate structures in a calcium-dependent manner and are involved in the tethering and rolling of leukocytes under physiological and pathological conditions. Three selectins have been identified: L-, P- and E-selectin. Current understanding of the glycosylation-dependent selectin function reveals a complex role for selectins and their ligands during inflammatory diseases. Among selectin ligands, mucin P-selectin glycoprotein ligand-1 (PSGL-1) binds all three selectins and has a well-documented role in organ targeting during inflammation in animal models. However, although inhibition of selectins and their ligands in animal models of inflammatory diseases has proven the validity of this approach in vivo, only a limited number of anti-selectin drugs have been tested in humans. Recent results obtained in clinical trials for asthma and psoriasis show that, although very challenging, the development of selectin antagonists holds concrete promise for the therapy of inflammatory diseases. PMID:18691137

  18. [Effect of dithranol therapy on membrane, basement membrane and nuclear markers in psoriasis lesions].

    PubMed

    Wollina, U; Schlesier, F; Schaarschmidt, H; Knopf, B; Hipler, C; Henkel, U; Roth, H; Bartá, U

    1987-02-15

    We investigated the effects of anti-psoriatic therapy with dithranol (1/20-1%) in salicylic acid (0.5%) in white petrolatum on lesional skin. FITC-labeled lectins and pemphigus vulgaris antibodies (PV) served as analytical means to study the glycocalyx. Antibodies of bullous pemphigoid (BP) were used as basal membrane markers. Nuclear antigens were recorded according to the binding of speckled, anti-nuclear antibodies (ANA) as well as antibodies to dsDNA. With some lectins, dithranol therapy resulted in pronounced fluorescence of the lower parts of the basal cells. ConA was fixed by the basal cell layer. To a lesser degree, ANA were fixed by nuclei of keratinocytes. PV antibodies were not fixed at all. PMID:3554801

  19. Inverse Psoriasis

    MedlinePlus

    ... Psoriatic Arthritis Info Kit Resources Community icon: Link text: Post your questions in our online community and ... psoriasis and psoriatic arthritis. Talk Psoriasis icon: Link text: Contact our Patient Navigators for free and confidential ...

  20. Erythrodermic Psoriasis

    MedlinePlus

    ... Psoriatic Arthritis Info Kit Resources Community icon: Link text: Post your questions in our online community and ... psoriasis and psoriatic arthritis. Talk Psoriasis icon: Link text: Contact our Patient Navigators for free and confidential ...

  1. Pustular Psoriasis

    MedlinePlus

    ... Psoriatic Arthritis Info Kit Resources Community icon: Link text: Post your questions in our online community and ... psoriasis and psoriatic arthritis. Talk Psoriasis icon: Link text: Contact our Patient Navigators for free and confidential ...

  2. Plaque Psoriasis

    MedlinePlus

    ... Psoriatic Arthritis Info Kit Resources Community icon: Link text: Post your questions in our online community and ... psoriasis and psoriatic arthritis. Talk Psoriasis icon: Link text: Contact our Patient Navigators for free and confidential ...

  3. Guttate Psoriasis

    MedlinePlus

    ... Psoriatic Arthritis Info Kit Resources Community icon: Link text: Post your questions in our online community and ... psoriasis and psoriatic arthritis. Talk Psoriasis icon: Link text: Contact our Patient Navigators for free and confidential ...

  4. About Psoriasis

    MedlinePlus

    ... Psoriatic Arthritis Info Kit Resources Community icon: Link text: Post your questions in our online community and ... psoriasis and psoriatic arthritis. Talk Psoriasis icon: Link text: Contact our Patient Navigators for free and confidential ...

  5. Psoriasis - guttate

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000822.htm Psoriasis - guttate To use the sharing features on this page, please enable JavaScript. Guttate psoriasis is a skin condition in which small, red, ...

  6. Itch in Psoriasis Management.

    PubMed

    Szepietowski, Jacek C; Reich, Adam

    2016-01-01

    Psoriasis is a common chronic inflammatory skin disease observed in about 1-3% of the general population. About 60-90% of patients with psoriasis suffer from itching. Interestingly, in the past itch was not considered as an important symptom of psoriasis. Despite the high frequency of itch in psoriasis, the pathogenesis of this symptom is still not fully elucidated. Although most studies indicate neurogenic inflammation and the role of neuropeptides, other mediators may be important as well. The majority of psoriatic patients consider itch as the most bothersome symptom of the disease as it significantly alters daily functioning and psychosocial well-being. Patients with itch showed greater impairment of their health-related quality of life compared to those without itch, and the intensity of itch correlated with the degree of quality-of-life reduction. However, treatment options for itch in psoriasis are limited. Therapy of itch in patients with psoriasis should be directed toward the resolution of skin lesions, as disease remission usually is linked with itch relief. Recent studies have clearly pointed to an important role of apremilast and biologic agents in itch intensity reduction in subjects suffering from psoriasis. Other treatment modalities include antihistamines, especially with a sedative effect, narrowband ultraviolet B, and antidepressants (doxepin, mirtazapine, paroxetine). Support by family members and/or health professionals may also be of importance in helping psoriatic subjects cope with itch. PMID:27578078

  7. [Psoriasis migrans : Erythema migrans as Koebner phenomenon in psoriasis].

    PubMed

    Ständer, S; Ständer, M; Thomas, P; Prinz, J C; Wolf, R

    2016-07-01

    Psoriasis is a chronic inflammatory disorder of the epidermis, which can be induced by systemic factors, such as streptococci infections or drugs. In addition, psoriasis can be caused by a local cutaneus trauma, known as Koebner phenomenon. Here, we describe a woman with psoriasis in remission, who developed a new psoriatic lesion due to a cutaneous infection with Borrelia burgdorferi. After causal therapy with doxycycline, the erythema migrans and psoriasis lesions disappeared. PMID:27106503

  8. Psoriasis: Pathogenesis, Assessment, and Therapeutic Update.

    PubMed

    Schleicher, Stephen M

    2016-07-01

    Psoriasis is a chronic condition that affects more than 7 million Americans. This article explores the pathogenesis and physical signs of psoriasis. Over the past 2 decades enhanced understanding of the immunologic basis of psoriasis has led to the development of new systemic agents that have revolutionized the management of this disease, and these modalities, along with traditional therapies, are described. PMID:27215156

  9. Options and opportunities for clinical management and treatment of psoriasis.

    PubMed

    Agrawal, Udita; Gupta, Madhu; Dube, Devyani; Vyas, Suresh P

    2013-01-01

    Psoriasis is a complex, multifactorial disease that appears to be influenced by immune-mediated components. For many years the pathogenesis of psoriasis has been discordant; the clinical picture suggested that the psoriasis was secondary to abnormal keratinocyte proliferation and differentiation, but later the role of the T cell was revealed. A variety of treatment options range from topical agents (e.g., coal tar, dithranol, and emollients for milder forms) to systemic agents (i.e., methotrexate or cyclosporin), and phototherapy. Recently, biologics have been added to this list that target particular steps in the immune or inflammatory pathways. Various nanocarriers (e.g., liposomes, niosomes, and microemulsions) have been successfully exploited for the delivery of several antipsoriatic drugs. This review provides insight into various psoriasis treatment strategies-from conventional to novel-currently in use or in development as well as the novel targets that have been explored and/or investigated for anti-psoriatic therapy. The pathogenesis of psoriasis and some of the topical, systemic biological, and novel approaches currently in use or in development are reviewed here. The pros and cons of each treatment strategy are presented, as are some of the animal models used to study features reminiscent of psoriasis. This information can be used to better the understanding of treatment options for this disease. PMID:23510110

  10. Pharmacokinetics of anti-psoriatic fumaric acid esters in psoriasis patients.

    PubMed

    Rostami-Yazdi, Martin; Clement, Bernd; Mrowietz, Ulrich

    2010-09-01

    The aim of this study was to evaluate pharmacokinetic parameters of fumaric acid esters (FAE) in psoriasis patients for the first time. For this prupose new HPLC assays were developed. Additionally, physicochemical parameters of FAE were determined, allowing a better interpretation of the in vivo data. In vivo, monomethylfumarate (MMF) and monoethylfumarate (MEF) were detected after t (lag) = 120 min. T (max) and c (max) of MMF were 210 min and 11.2 microM, respectively, 210 min and 5.2 microM for MEF. The half-life of MMF was 38.7 min, and 25.4 min of MEF. The AUC(0-infinity) of MMF was 172 min microg ml(-1) and 63.6 min microg ml(-1) of MEF. Data display median of three subjects. No plasma levels of dimethylfumarate (DMF) or fumaric acid (FA) were detected. The evaluation of physicochemical parameters of FAE showed that only DMF fulfils the criteria of Lipinski's rule of five. The pKa of MMF was determined as 3.63. The data of this study provide evidence that DMF is most likely absorbed out of the duodenum into the presystemic circulation and is not completely hydrolysed to MMF before uptake as assumed by others. PMID:20574745

  11. PSORIASIS IN CHILDREN: AN INSIGHT

    PubMed Central

    Dhar, Sandipan; Banerjee, Raghubir; Agrawal, Nilesh; Chatterjee, Sharmila; Malakar, Rajib

    2011-01-01

    Onset of psoriasis in childhood is quite common. Chronicity, inflammation and hyperproliferation are the cardinal features by which the condition establishes its uniqueness. Clearance of disease may be farfetched in most patients and relapse is frequent. Early recognition and management of psoriasis in children and adolescents is vital in therapy in children. PMID:21772584

  12. IL-8/IL-8 receptor expression in psoriasis and the response to systemic tacrolimus (FK506) therapy.

    PubMed Central

    Lemster, B H; Carroll, P B; Rilo, H R; Johnson, N; Nikaein, A; Thomson, A W

    1995-01-01

    Recently, the keratinocyte IL-8/IL-8 receptor (IL-8R) pathway has been implicated in the pathogenesis of psoriasis, and there is evidence that the potent macrolide immune suppressant tacrolimus (formerly FK506) can inhibit this pathway in vitro. In this study, determination of the expression of cytokine mRNAs in lesional skin of patients with active disease by reverse transcriptase polymerase chain reaction revealed transcripts for IL-1 beta, tumour necrosis factor-alpha (TNF-alpha), IL-6, IL-8, IL-8R, IL-10, interferon-gamma (IFN-gamma), IL-2R and transforming growth factor-beta (TGF-beta), but not IL-2 or IL-4. IL-8 was the only cytokine expressed in affected skin of all patients but not in clinically normal skin of healthy subjects. In seven CD4+ T cell clones propagated from the lesional skin of an untreated psoriasis patient, IL-8 was expressed by the skin-derived T lymphocytes and not by feeder cells (irradiated autologous blood lymphocytes); IL-1 beta, IL-2, IL-6 and IL-10 were also expressed by some or all of the T cell clones. IL-8 mRNA was not detected in the skin of any patient after the start of systemic tacrolimus therapy; IL-1 beta, IL-6 and IFN-gamma transcripts were also reduced. By 12 weeks, the mean psoriasis area and severity index (PASI) had decreased from 18.8 to 3.8, a reduction of 80%. In the same post-treatment biopsies, however, message for IL-8R persisted. Estimation of circulating IL-8 levels by enzyme immunoassay showed that all patients with detectable IL-8 before treatment had decreased levels in response to treatment with tacrolimus; reductions in PASI scores were accompanied by decreases in IL-8 levels, that varied both in rate and extent. Partial relapse, which in a minority of patients followed the initial period of remission, and was precipitated by drug dose reduction, was accompanied by an increase in circulating IL-8. These findings add credence to the view that the IL-8/IL-8R autocrine/paracrine pathway may be important in the

  13. COMPARATIVE THERAPEUTIC EVALUATION OF DIFFERENT TOPICALS AND NARROW BAND ULTRAVIOLET B THERAPY COMBINED WITH SYSTEMIC METHOTREXATE IN THE TREATMENT OF PALMOPLANTAR PSORIASIS

    PubMed Central

    Gupta, Sunil K; Singh, K K; Lalit, Mohan

    2011-01-01

    Background: The incidence of uncomplicated psoriasis is 1–3% in the general population. The involvement of palm and sole is seen in 7–14.5% of cases. There are different topicals and systemic therapies available for treating the case of psoriasis but none is satisfactory for longer duration. Aim: The study involved the comparative therapeutic evaluation of the different topical regimens and narrow band ultraviolet B (NB-UVB) therapy in combination with systemic methotrexate. Materials and Methods: The study was held in out-patient department of Skin, VD and Leprosy of B.R.D. Medical College, Gorakhpur, from July 2007 to December 2008. The group included 98 new cases of palmoplantar psoriasis. These cases were divided into eight groups according to the eight regimens involved in the study. The severity of psoriasis was assessed by the ESIF (erythema, scaling, induration and fissuring) score. Results: The study showed that all the regimens had significant response rates. The combination of NB-UVB with systemic methotrexate had maximum response rate (64.85±4.52%) that was statistically significant (paired “t” at 16d.f. = 33.329, P<0.001) with minimum number of recurrences after stopping the treatment. The combination of halobetasol ointment with systemic methotrexate also had significant response rate (paired “t” at 19d.f. = 13.5183, P<0.001) but had maximum number of cases with recurrence (70%) after stopping the treatment. Conclusion: These results suggest that the combination of every regimen with systemic methotrexate resulted in an early and a good improvement in the quality of life of patients suffering from psoriasis. It also shows that NB-UVB in combination with systemic methotrexate is more efficacious and has minimum recurrence rate and side effects in the treatment of palmoplantar psoriasis. PMID:21716541

  14. Anti-VEGF Therapies in the Clinic

    PubMed Central

    Meadows, Kellen L.; Hurwitz, Herbert I.

    2012-01-01

    The development and use of antiangiogenesis agents, particularly those targeting vascular endothelial growth factor (VEGF), has become an integral component of anticancer regimens for many tumor types. This review is intended to highlight some of the most important clinical successes and failures of anti-VEGF therapies, and where possible, to suggest important lessons that have been learned. This review emphasizes data from agents that have been FDA approved and/or have completed phase III studies. PMID:23028128

  15. New and emerging biologic therapies for moderate-to-severe plaque psoriasis: mechanistic rationales and recent clinical data for IL-17 and IL-23 inhibitors

    PubMed Central

    Gaspari, Anthony A; Tyring, Stephen

    2015-01-01

    The development of effective and well-tolerated biologic therapies has advanced the management of psoriasis by enabling clinicians to treat underlying disease mechanisms. Biologics approved for the treatment of moderate-to-severe psoriasis include three tumor necrosis factor alpha inhibitors and an interleukin-12/interleukin-23 inhibitor. The establishment of the immunological basis of psoriasis has led to the development of biologic agents targeting specific downstream mediators in the psoriatic cascade. These drugs inhibit cytokines and cytokine signaling/transcription mediators like interleukin-17, which plays an important role in immunopathogenesis. Several interleukin-17 inhibitors are undergoing phase 3 clinical studies. In addition, biologics that selectively inhibit interleukin-23 have been assessed in phase 2 studies. This review describes how the dissection of pathways in the immunopathogenesis of psoriasis has led to the development of therapeutic agents and highlights the latest clinical efficacy, safety and tolerability data on new and emerging biologic therapies that selectively target interleukin-17 or interleukin-23. PMID:26201310

  16. Comparison of ethosomes and liposomes for skin delivery of psoralen for psoriasis therapy.

    PubMed

    Zhang, Yong-Tai; Shen, Li-Na; Wu, Zhong-Hua; Zhao, Ji-Hui; Feng, Nian-Ping

    2014-08-25

    Recent reports have indicated that psoriasis may be caused by malfunctioning dermal immune cells, and psoralen ultraviolet A (PUVA) is an effective treatment for this chronic disease. However, conventional topical formulations achieve poor drug delivery across patches of psoriasis to their target sites. The present study describes the development of a novel psoralen transdermal delivery system employing ethosomes, flexible vesicles that can penetrate the stratum corneum and target deep skin layers. An in vitro skin permeation study showed that the permeability of psoralen-loaded ethosomes was superior to that of liposomes. Using ethosomes, psoralen transdermal flux and skin deposition were 38.89±0.32 μg/cm(2)/h and 3.87±1.74 μg/cm(2), respectively, 3.50 and 2.15 times those achieved using liposomes, respectively. The ethosomes and liposomes were found to be safe following daily application to rat skin in vivo, for 7 days. The ethosomes showed better biocompatibility with human embryonic skin fibroblasts than did an equivalent ethanol solution, indicating that the phosphatidylcholine present in ethosome vesicles improved their biocompatibility. These findings indicated that ethosomes could potentially improve the dermal and transdermal delivery of psoralen and possibly of other drugs requiring deep skin delivery. PMID:24907596

  17. Biologic Safety in Psoriasis

    PubMed Central

    Mansouri, Yasaman

    2015-01-01

    The development of targeted biologic agents has revolutionized the treatment of psoriasis. In this review, the authors focus on the published long-term (≥ one year) safety data for the use of tumor necrosis factor-α antagonists etanercept, infliximab, and adalimumab, as well as the IL-12/IL-23 antagonist ustekinumab, in adult patients with moderate-to-severe psoriasis. The efficacy of these currently available biologic therapies has been demonstrated in several studies, and their safety profiles are also reassuring. PMID:25741401

  18. Antibodies in the Treatment of Psoriasis: IL-12/23 p40 and IL-17a.

    PubMed

    Leonardi, Craig L

    2016-06-01

    The anti-tumor necrosis factor (TNF)-α agents represent the second generation of psoriasis therapy. Research has produced a third generation of biologic treatments, some of which offer greater efficacy than the TNF-α inhibitors. This article reviews the data documenting the efficacy and safety of three types of biologics. PMID:27551698

  19. Management of psoriasis in adolescence

    PubMed Central

    Fotiadou, Christina; Lazaridou, Elizabeth; Ioannides, Demetrios

    2014-01-01

    Psoriasis is a chronic inflammatory cutaneous disorder affecting 2%–4% of the world’s population. The prevalence of the disease in childhood and adolescence ranges between 0.5% and 2%. The management of psoriasis in adolescence is an intriguing and complicated task. Given the paucity of officially approved therapies, the very limited evidence-based data from randomized controlled trials, and the absence of standardized guidelines, physicians must rely on published experience from case reports both from the field of dermatology as well as from the application of these drugs for other pediatric conditions coming from the disciplines of rheumatology, gastroenterology, and oncology. Psoriatic adolescents deal with a potentially disfiguring and lifelong disease that could permanently impair their psychological development. It must be clarified to them that psoriasis does not have a permanent cure, and therefore the main goal of treatments is to establish disease control and prolonged periods between flares. The majority of adolescents suffer from mild psoriasis, and thus they are treated basically with topical treatment modalities. Phototherapy is reserved for adolescents with mild-to-moderate plaque disease and/or guttate psoriasis when routine visits to specialized centers do not create practical problems. Systemic agents and biologics are administered to patients with moderate-to-severe plaque psoriasis, pustular psoriasis, or erythrodermic psoriasis. PMID:24729738

  20. Adolescent Scalp Psoriasis

    PubMed Central

    Gomez, Barbara

    2015-01-01

    Plaque psoriasis can begin early in life and negatively affect quality of life. Topical agents are generally recommended as first-line therapy for plaque psoriasis. The synergy of a vitamin D analog and a steroid in a topical fixed-combination formulation provides more favorable effectiveness and tolerability as compared with either agent alone. The safety and effectiveness of a once-daily calcipotriene/betamethasone dipropionate topical suspension have been established in children 12 to 17 years of age with scalp plaque psoriasis. Combination topical formulations and once-daily dosing decrease regimen complexity and may increase adherence. Accommodation of vehicle preference may also improve adherence and real-life effectiveness. PMID:26203320

  1. [Pathogenesis of psoriasis].

    PubMed

    Schäkel, K; Schön, M P; Ghoreschi, K

    2016-06-01

    Psoriasis is an inflammatory T cell-mediated autoimmune disease of skin and joints that affects 2-4 % of the adult population and 0.1-1 % of children. Genetic susceptibility, environmental triggering factors, and innate immune processes initiate psoriasis pathogenesis that results in an adaptive autoreactive response. The T cell response is orchestrated by CD 8(+) T cells in the epidermis and by CD 4(+) T cells in the dermis that predominantly produce interleukin-17 (IL‑17). Research of the past 15 years unraveled cellular and molecular mechanisms as well as cytokines like TNF-α or IL‑23 that contribute to psoriatic inflammation. This knowledge has been translated into clinical practice and a number of antipsoriatic small molecules and immunobiologics are now available. Here, we discuss the current principles of psoriasis pathogenesis in the context of modern therapies. PMID:27246016

  2. Evading anti-angiogenic therapy: resistance to anti-angiogenic therapy in solid tumors

    PubMed Central

    Dey, Nandini; De, Pradip; Brian, Leyland-Jones

    2015-01-01

    Vascular endothelial growth factor (VEGF) dependent tumor angiogenesis is an essential step for the initiation and promotion of tumor progression. The hypothesis that VEGF-driven tumor angiogenesis is necessary and sufficient for metastatic progression of the tumor, has been the major premise of the use of anti-VEGF therapy for decades. While the success of anti-VEGF therapy in solid tumors has led to the success of knowledge-based-therapies over the past several years, failures of this therapeutic approach due to the development of inherent/acquired resistance has led to the increased understanding of VEGF-independent angiogenesis. Today, tumor-angiogenesis is not a synonymous term to VEGF-dependent function. The extensive study of VEGF-independent angiogenesis has revealed several key factors responsible for this phenomenon including the role of myeloid cells, and the contribution of entirely new phenomenon like vascular mimicry. In this review, we will present the cellular and molecular factors related to the development of anti-angiogenic resistance following anti-VEGF therapy in different solid tumors. PMID:26692917

  3. Evading anti-angiogenic therapy: resistance to anti-angiogenic therapy in solid tumors.

    PubMed

    Dey, Nandini; De, Pradip; Brian, Leyland-Jones

    2015-01-01

    Vascular endothelial growth factor (VEGF) dependent tumor angiogenesis is an essential step for the initiation and promotion of tumor progression. The hypothesis that VEGF-driven tumor angiogenesis is necessary and sufficient for metastatic progression of the tumor, has been the major premise of the use of anti-VEGF therapy for decades. While the success of anti-VEGF therapy in solid tumors has led to the success of knowledge-based-therapies over the past several years, failures of this therapeutic approach due to the development of inherent/acquired resistance has led to the increased understanding of VEGF-independent angiogenesis. Today, tumor-angiogenesis is not a synonymous term to VEGF-dependent function. The extensive study of VEGF-independent angiogenesis has revealed several key factors responsible for this phenomenon including the role of myeloid cells, and the contribution of entirely new phenomenon like vascular mimicry. In this review, we will present the cellular and molecular factors related to the development of anti-angiogenic resistance following anti-VEGF therapy in different solid tumors. PMID:26692917

  4. Anti-Atherosclerotic Therapy Based on Botanicals

    PubMed Central

    Orekhov, Alexander N.; Sobenin, Igor A.; Korneev, Nikolay V.; Kirichenko, Tatyana V.; Myasoedova, Veronika A.; Melnichenko, Alexandra A.; Balcells, Mercedes; Edelman, Elazer R.; Bobryshev, Yuri V.

    2015-01-01

    Natural products including botanicals for both therapy of clinical manifestations of atherosclerosis and reduction of atherosclerosis risk factors are topics of recent patents. Only a few recent patents are relevant to the direct anti-atherosclerotic therapy leading to regression of atherosclerotic lesions. Earlier, using a cellular model we have developed and patented several anti-atherosclerotic drugs. The AMAR (Atherosclerosis Monitoring and Atherogenicity Reduction) study was designed to estimate the effect of two-year treatment with time-released garlic-based drug Allicor on the progression of carotid atherosclerosis in 196 asymptomatic men aged 40–74 in double-blinded placebo-controlled randomized clinical study. The primary outcome was the rate of atherosclerosis progression, measured by high-resolution B-mode ul-trasonography as the increase in carotid intima-media thickness (IMT) of the far wall of common carotid arteries. The mean rate of IMT changes in Allicor-treated group (−0.022±0.007 mm per year) was significantly different (P = 0.002) from the placebo group in which there was a moderate progression of 0.015±0.008 mm at the overall mean baseline IMT of 0.931±0.009 mm. A significant correlation was found between the changes in blood serum atherogenicity (the ability of serum to induce cholesterol accumulation in cultured cells) during the study and the changes in intima-media thickness of common carotid arteries (r = 0.144, P = 0.045). Thus, the results of AMAR study demonstrate that long-term treatment with Allicor has a direct anti-atherosclerotic effect on carotid atherosclerosis and this effect is likely to be due to serum atherogenicity inhibition. The beneficial effects of other botanicals including Inflaminat (calendula, elder and violet), phytoestrogen-rich Karinat (garlic powder, extract of grape seeds, green tea leafs, hop cones, β-carotene, α-tocopherol and ascorbic acid) on atherosclerosis have also been revealed in clinical

  5. The potential of the essential fatty acid-deficient hairless rat as a psoriasis screening model for topical anti-proliferative drugs.

    PubMed

    Jensen, Monika; Groth, Lotte; Hølmer, Gunhild; Hansen, Harald S; Fullerton, Ann

    2002-01-01

    The objective of this study was to establish essential fatty acid deficiency (EFAD) in hairless rats and investigate the potential of this model as a psoriasis screening model by testing the effects of calcipotriol and dithranol on differentiation and proliferation in the epidermis. Hairless rats were fed with a fat-free diet lacking linoleic acid. The EFAD condition was established within 8 weeks. In order to ensure that this condition had been established, several parameters were measured and observed, i.e. animal weight, water consumption, transepidermal water loss, clinical skin symptoms, histology of the epidermis and fatty acid analysis of serum and skin. Immediately after the EFAD condition had been established, the animals were treated with dithranol ointment or different concentrations of calcipotriol solution. A reduction in epidermal thickness of 15-20% was seen after the treatment with calcipotriol. Dithranol and its coal tar-containing vehicle also showed a reductive effect on epidermal thickness. EFAD hairless rats possess various histological changes resembling psoriasis. These histological changes normalise during treatment with anti-psoriatic drugs as calcipotriol, dithranol and coal tar. The results of the present study indicate that the EFAD rat may be a useful model for studies of anti-psoriatic drugs affecting cell proliferation. PMID:12476014

  6. Psoriasis - guttate

    MedlinePlus

    ... certain heart conditions Stress Sunburn Too much alcohol Psoriasis may be severe in persons who have a weakened immune system. This may include persons who have: HIV/ AIDS Autoimmune disorders , including rheumatoid arthritis Chemotherapy for cancer

  7. Current management of scalp psoriasis.

    PubMed

    Guenther, L

    2015-01-01

    The scalp is involved in up to 80% of individuals with psoriasis. Eighty percent of those with scalp psoriasis experience a negative impact on quality of life. Topical treatment with corticosteroids with or without vitamin D3 analogues is the mainstay of treatment. Topical therapy most suitable for the scalp is formulated as a solution, lotion, gel, foam, spray, oil, or shampoo. Twice weekly maintenance in frequent relapsers may decrease the time to first relapse. Intralesional steroids, phototherapy and the excimer laser are occasionally used for resistant cases. In patients with moderate-to-severe psoriasis, apremilast, adalimumab and etanercept have been shown to significantly improve scalp psoriasis. They should be considered in patients who have failed topical therapy. PMID:26382557

  8. Management of childhood psoriasis.

    PubMed

    Cordoro, Kelly M

    2008-01-01

    Treating children with psoriasis represents one of the most rewarding yet constantly challenging endeavors in dermatology. These patients require time, energy, enthusiasm, empathy, and current, comprehensive knowledge of the unique clinical presentations in children and available therapies, including clinical action spectrum, mechanism of action, potential toxicity, and monitoring. Longitudinal trials examining the epidemiology and natural history of psoriasis, as well as the safety and efficacy of current and emerging treatments, are desperately needed in the pediatric population. Partner with the patient, family, and other multidisciplinary providers to form an educational and therapeutic alliance. Early in the course of disease, schedule frequent visits for reinforcement of the therapeutic plan, education, clinical and treatment monitoring, and support. As the disease and the patient's physical, psychosocial and emotional level of functioning evolve, so too will the requirement for follow-up and monitoring. Patient advocacy and education groups, such as the National Psoriasis Foundation (www.psoriasis.org; 800-723-9166) are excellent resources and can serve as an extension of your comprehensive care. PMID:19256308

  9. Nail psoriasis: a review of the literature*

    PubMed Central

    Schons, Karen Regina Rosso; Knob, Cristiane Faccin; Murussi, Nádia; Beber, André Avelino Costa; Neumaier, Walter; Monticielo, Odirlei André

    2014-01-01

    Nails are considered epidermal appendages, and as such, are commonly affected in patients with psoriasis, 80% of whom are likely to develop nail psoriasis as a result of their condition. Two patterns of nail disorders have been shown to be caused by psoriasis. Nail matrix involvement can result in features such as leukonychia, pitting (punctures or cupuliform depressions), red spots in the lunula and crumbling. Nail bed involvement, on the other hand, can cause onycholysis, salmon or oil-drop patches, subungual hyperkeratosis and splinter hemorrhages. Nail disease causes aesthetic and functional impairment, and is indicative of more severe forms of psoriasis as well as of joint involvement. The treatment for nail psoriasis involves behavioral interventions, topical medications, or systemic therapy in case of extensive skin or joint involvement. This article presents a review of the main features of nail psoriasis, its clinical presentation, diagnostic and assessment methods, clinical repercussions, and of its available treatment options. PMID:24770509

  10. Improving outcomes in patients with psoriasis.

    PubMed

    Tidman, Michael J

    2013-01-01

    Psoriasis is a heterogeneous inflammatory disorder that targets the skin and joints. It affects 1.3-2% of the population. The diagnosis of plaque psoriasis is usually straightforward, a helpful diagnostic clue is the tendency for silver scales to appear after gentle scratching of a lesion. Stress, streptococcal infection and drugs including beta-blockers, antimalarials and lithium may precipitate or exacerbate psoriasis. Psoriasis, especially when severe, predisposes to metabolic syndrome, and patients with psoriasis are at increased risk of ischaemic heart disease, hypertension, stroke, type 2 diabetes and hyperlipidaemia. Additionally, psoriasis sufferers appear at increased risk of uveitis, inflammatory boweldisease, lymphoma, non-melanoma skin cancer, COPD and venous thromboembolism. Psoriasis should be assessed on the basis of: severity, impact on physical, psychological and social wellbeing, symptoms of arthritis and the presence of comorbidities. Poor response to topical therapy may be as much to do with lack of compliance as with lack of efficacy. The number of treatments each day should be kept to a minimum, and patients should be reviewed after four weeks when initiating or changing topical therapy to improve adherence to treatment and assess response. The majority of patients with psoriasis can be managed in primary care, although specialist care may be necessary at some point in up to 60% of cases. Patients with erythrodermic or generalised pustular psoriasis should be referred for a same day dermatological opinion, and if psoriatic arthritis is suspected, early referral for a rheumatological opinion is recommended. PMID:23469725

  11. Anti-Vascular Endothelial Growth Factor Therapy in Breast Cancer

    PubMed Central

    Kristensen, Tina Bøgelund; Knutsson, Malin L. T.; Wehland, Markus; Laursen, Britt Elmedal; Grimm, Daniela; Warnke, Elisabeth; Magnusson, Nils E.

    2014-01-01

    Neo-angiogenesis is a critical process for tumor growth and invasion and has become a promising target in cancer therapy. This manuscript reviews three currently relevant anti-angiogenic agents targeting the vascular endothelial growth factor system: bevacizumab, ramucirumab and sorafenib. The efficacy of anti-angiogenic drugs in adjuvant therapy or as neo-adjuvant treatment has been estimated in clinical trials of advanced breast cancer. To date, the overall observed clinical improvements are unconvincing, and further research is required to demonstrate the efficacy of anti-angiogenic drugs in breast cancer treatments. The outcomes of anti-angiogenic therapy have been highly variable in terms of tumor response. New methods are needed to identify patients who will benefit from this regimen. The development of biomarkers and molecular profiling are relevant research areas that may strengthen the ability to focus anti-angiogenic therapy towards suitable patients, thereby increase the cost-effectiveness, currently estimated to be inadequate. PMID:25514409

  12. Telocyte dynamics in psoriasis

    PubMed Central

    Manole, CG; Gherghiceanu, Mihaela; Simionescu, Olga

    2015-01-01

    The presence of telocytes (TCs) as distinct interstitial cells was previously documented in human dermis. TCs are interstitial cells completely different than dermal fibroblasts. TCs are interconnected in normal dermis in a 3D network and may be involved in skin homeostasis, remodelling, regeneration and repair. The number, distribution and ultrastructure of TCs were recently shown to be affected in systemic scleroderma. Psoriasis is a common inflammatory skin condition (estimated to affect about 0.1–11.8% of population), a keratinization disorder on a genetic background. In psoriasis, the dermis contribution to pathogenesis is frequently eclipsed by remarkable epidermal phenomena. Because of the particular distribution of TCs around blood vessels, we have investigated TCs in the dermis of patients with psoriasis vulgaris using immunohistochemistry (IHC), immunofluorescence (IF), and transmission electron microscopy (TEM). IHC and IF revealed that CD34/PDGFRα-positive TCs are present in human papillary dermis. More TCs were present in the dermis of uninvolved skin and treated skin than in psoriatic dermis. In uninvolved skin, TEM revealed TCs with typical ultrastructural features being involved in a 3D interstitial network in close vicinity to blood vessels in contact with immunoreactive cells in normal and treated skin. In contrast, the number of TCs was significantly decreased in psoriatic plaque. The remaining TCs demonstrated multiple degenerative features: apoptosis, membrane disintegration, cytoplasm fragmentation and nuclear extrusion. We also found changes in the phenotype of vascular smooth muscle cells in small blood vessels that lost the protective envelope formed by TCs. Therefore, impaired TCs could be a ‘missed’ trigger for the characteristic vascular pathology in psoriasis. Our data explain the mechanism of Auspitz’s sign, the most pathognomonic clinical sign of psoriasis vulgaris. This study offers new insights on the cellularity of

  13. Efficacy, tolerability and safety of switching from etanercept to infliximab for the treatment of moderate-to-severe psoriasis: A multicenter, open-label trial (TANGO).

    PubMed

    Ayala, Fabio; Lambert, Julien

    2015-01-01

    Biologic anti-tumor necrosis factor-α (anti-TNF-α) therapies have revolutionized the management of psoriasis. However, despite similar mechanisms of action, inter-patient variability in the clinical responses to therapy remain unexplained. Possible differences between agents include stability or bioavailability and anti-drug antibody development, and patient factors such as compliance may play a role. As a result, it is not uncommon for physicians to switch a patient from one anti-TNF-α agent to another when initial response is inadequate. This multicenter, single-arm, observational, Phase IV study assessed the efficacy and safety of infliximab therapy in patients with moderate-to-severe psoriasis who had not responded to 24 weeks' etanercept treatment. Drug efficacy was assessed using specific psoriasis indexes; health-related quality of life (HRQoL) was measured using the Dermatology Life Quality Index and the Skindex-29. A total of 48 patients were screened, 38 were treated with infliximab and 31 completed the study. Of these, 71% achieved Psoriasis Area and Severity Index 75 after 10 weeks, and improvement in HRQoL was documented. The results of this study showed that patients with moderate-to-severe psoriasis could be successfully switched from etanercept to infliximab, with improvements in both clinical parameter and HRQoL. PMID:25231176

  14. Psoriasis: Pregnancy and Nursing

    MedlinePlus

    ... to find out more! Email * Zipcode Pregnancy and Nursing In general, psoriasis does not affect the male ... psoriasis and birth » Treating psoriasis while pregnant or nursing There is little research on the impact of ...

  15. What Is Psoriasis?

    MedlinePlus

    ... Information Psoriasis Find a Clinical Trial Journal Articles Psoriasis PDF Version Size: 54 KB Audio Version Time: ... Size: 6.4 MB November 2014 What Is Psoriasis? Fast Facts: An Easy-to-Read Series of ...

  16. [THE DYNAMICS OF IMMUNOLOGICAL RESULTS OF PATIENTS WITH T-CELL SKIN LYMPHOMAS AND PSORIASIS BY THE THERAPY OF ACTIVATION MECHANISMS SANOGENESIS METHODS].

    PubMed

    Kurgan, D M; Kokoruz, M V; Kurgan, M G; Novak, V L

    2015-01-01

    The therapy T-cell skin lymphoma and psoriasis by the application of activation mechanisms sanogenesis methods, such as: original--a treatment plasmapheresis, a standard heparin infusion; used for the first time--wobenzym; solutions of acid acetic food and sodium bicarbonate; known--the basic sanitations of concomitant diseases, photopheresis caused remissions in 79.6% patients with different stages T-cell skin lymphoma (observed over an 8-year span), and in 67% of patients with psoriasis (observed over an 6-year span). Depuration reactions (phagocytosis, pinocytosis, toxin neutralization) has been activated by detoxication of treatment plasmapheresis and heparin infusions. The topical therapy with wobenzym, solutions of acid acetic food and sodium bicarbonate renewed natural immune barrier of skin. Basic therapy of concomitant diseases enhanced of patient state of health and mobilized compensatory resources. Photopheresis initiated autoimmunization processes by malignant CD4+ lymphocytes. When remission was achieved, the parameters of cellular and humoral immunity returned to normal levels, or the parameters made worse in the absence of remission. PMID:26827436

  17. Systemic Treatment of Pediatric Psoriasis: A Review.

    PubMed

    Napolitano, Maddalena; Megna, Matteo; Balato, Anna; Ayala, Fabio; Lembo, Serena; Villani, Alessia; Balato, Nicola

    2016-06-01

    Psoriasis is a chronic, immune-mediated, inflammatory skin disease, affecting 1-3% of the white population. Although the existence of two psoriasis incidence peaks has been suggested (one in adolescence before 20 years of age and another in adulthood), its onset may occur at any age, including childhood and adolescence, in which the incidence is now estimated at 40.8 per 100,000. As for adult psoriasis, pediatric psoriasis has recently been associated with obesity, metabolic syndrome, increased waist circumference percentiles and metabolic laboratory abnormalities, warranting early monitoring and lifestyle modifications. In addition, due to psoriasis' chronic nature and frequently occurring relapses, psoriatic patients tend to have an impaired quality of life, often requiring long-term treatment. Therefore, education of both pediatric patients and their parents is essential to successful and safe disease management. Given the lack of officially approved therapies, the very limited evidence-based data from randomized controlled trials, and the absence of standardized guidelines, to date, pediatric psoriasis treatment is primarily based on published case reports, case series, guidelines for adult psoriasis, expert opinions and experience with these drugs in other pediatric disorders coming from the disciplines of rheumatology, gastroenterology and oncology. This review focuses on the use of systemic treatments in pediatric psoriasis and their specific features, analyzing the few literature evidences available, expanding the treatment repertoire and guiding dermatologists in better managing of recalcitrant pediatric psoriasis. PMID:27085539

  18. The single-chain anti-TNF-α antibody DLX105 induces clinical and biomarker responses upon local administration in patients with chronic plaque-type psoriasis.

    PubMed

    Tsianakas, Athanasios; Brunner, Patrick M; Ghoreschi, Kamran; Berger, Claudia; Loser, Karin; Röcken, Martin; Stingl, Georg; Luger, Thomas; Jung, Thomas

    2016-06-01

    It is not clear whether TNF-α antagonists used in the treatment of psoriasis need to act systemically, or whether local inhibition of skin-produced TNF-α would be sufficient to silence skin inflammation. To answer this question, we conducted two multicentre, double-blinded, randomized, placebo-controlled clinical trials with the novel single-chain anti-TNF-α-PENTRA(®) -antibody DLX105. Upon intra-dermal injection, DLX105 induced a mean local PASI decrease of 33% over baseline after 2 weeks of treatment, while the placebo response was only 12% (P = 0.001). The clinical response was accompanied by changes in biomarkers such as reductions in K16, Ki67 and epidermal thickness as well as decreased mRNA levels of IL-17, TNF-α, IL-23p19, IL-12p40 and IFN-γ. Next, we applied the drug topically twice daily in a 0.5% hydrogel formulation. While the local PASI did not change, topical DLX105 mediated significant reductions of mRNA levels of key proinflammatory cytokines when compared to placebo, and this effect was further enhanced after weekly tape stripping of plaques to increase drug penetration. These results suggest that longer treatment periods and/or increased local drug concentrations might result in better therapeutic efficacy of topically applied DLX105. In sum, we can show for the first time that local inhibition of TNF-α is sufficient to mediate a biological response in psoriasis that translates into clinical efficacy. PMID:26738450

  19. A Preliminary, Open Label, Single-arm Study of Calcipotriene/Betamethasone Topical Suspension as a Supplement to Non-biologic Systemic Therapy for Psoriasis

    PubMed Central

    Kupetsky, Erine; Houston, Neil A.M.

    2016-01-01

    Background: Calcipotriene/betamethasone topical suspension is a topical therapy that is often used as monotherapy as a first-line treatment for plaque psoriasis. The objective of this preliminary, open label, single arm study was to determine the efficacy of adding a topical suspension to a traditional systemic therapy for psoriasis, either methotrexate or acitretin. Methods: In this exploratory study, eight patients with chronic plaque psoriasis who were on stable methotrexate or acitretin treatment without clearance were treated with once-daily calcipotriene/betamethasone topical suspension. Subjects completed five study visits over 12 weeks. Primary outcome measure was improvement of two or more points in Investigator Global Assessment. Secondary endpoints included change in Body Surface Area, Dermatology Life Quality Index, and Patient’s Global Assessment from baseline to Week 12. Results: Overall, the median decrease in Investigator Global Assessment over 12 weeks was 1.5 points, with 50 percent of subjects experiencing a drop of two or more points in Investigator Global Assessment. All eight subjects had a reduction in Body Surface Area and Patient’s Global Assessment. There was a mean decrease in Dermatology Life Quality Index score of 78.9 percent, showing improved patient quality of life. In addition, all patients tolerated the treatment well and 6 of 8 patients had improved satisfaction level with their treatment by the end of the study. Conclusion: The topical suspension was effective and well-tolerated in conjunction with stable methotrexate or acitretin treatment in all eight patients in this study. These results support the feasibility of a larger scale study to further investigate the efficacy of these treatment combinations. The trial is registered at ClinicalTrials.gov, number NCT01761019. PMID:27462386

  20. Differential Drug Survival of Biologic Therapies for the Treatment of Psoriasis: A Prospective Observational Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR).

    PubMed

    Warren, Richard B; Smith, Catherine H; Yiu, Zenas Z N; Ashcroft, Darren M; Barker, Jonathan N W N; Burden, A David; Lunt, Mark; McElhone, Kathleen; Ormerod, Anthony D; Owen, Caroline M; Reynolds, Nick J; Griffiths, Christopher E M

    2015-11-01

    Drug survival reflects a drug's effectiveness, safety, and tolerability. We assessed the drug survival of biologics used to treat psoriasis in a prospective national pharmacovigilance cohort (British Association of Dermatologists Biologic Interventions Register (BADBIR)). The survival rates of the first course of biologics for 3,523 biologic-naive patients with chronic plaque psoriasis were compared using survival analysis techniques and predictors of discontinuation analyzed using a multivariate Cox proportional hazards model. Data for patients on adalimumab (n=1,879), etanercept (n=1,098), infliximab (n=96), and ustekinumab (n=450) were available. The overall survival rate in the first year was 77%, falling to 53% in the third year. Multivariate analysis showed that female gender (hazard ratio (HR) 1.22; 95% confidence interval (CI): 1.09-1.37), being a current smoker (HR 1.19; 95% CI: 1.03-1.38), and a higher baseline dermatology life quality index (HR 1.01; 95% CI: 1.00-1.02) were predictors of discontinuation. Presence of psoriatic arthritis (HR 0.82; 95% CI: 0.71-0.96) was a predictor for drug survival. As compared with adalimumab, patients on etanercept (HR 1.63; 95% CI: 1.45-1.84) or infliximab (HR 1.56; 95% CI: 1.16-2.09) were more likely to discontinue therapy, whereas patients on ustekinumab were more likely to persist (HR 0.48; 95% CI: 0.37-0.62). After accounting for relevant covariates, ustekinumab had the highest first-course drug survival. The results of this study will aid clinical decision making when choosing biologic therapy for psoriasis patients. PMID:26053050

  1. Psoriasis and psoriatic arthritis treatment.

    PubMed

    Menter, Alan

    2016-06-01

    Over the past several years, an increased understanding of the pathophysiology of psoriasis and psoriatic arthritis (PsA) has led to the development of several new biologic therapies. Appropriate treatment selection and timing may slow, and even halt, the progression of psoriasis and PsA; as a result, it can decrease the economic burden. As treatment options vary based on individual disease characteristics and patient preferences, reviewing the patient's complete clinical picture is imperative. An updated treatment algorithm, based on patients' most severe disease domain, is now available to guide the selection of optimal therapy. Special care should be given to patients with both psoriasis and PsA who experience multiple disease domains, a heavy symptom burden, and an increased risk of comorbidities. PMID:27356194

  2. Erythrodermic psoriasis: current and future role of biologicals.

    PubMed

    Stinco, Giuseppe; Errichetti, Enzo

    2015-04-01

    Erythrodermic psoriasis (EP) is a severe form of psoriasis that may be associated with serious and sometimes fatal complications. The treatment of EP is often a challenge, since several factors, including treatment failure or possible complications, may limit favorable outcomes with traditional drugs. Recent evidence suggests that biological drugs, including both anti-tumor necrosis factor alpha agents and ustekinumab, may be useful in improving the management of EP. Unfortunately, since subjects with EP are usually excluded from pivotal trials involving biological agents, this evidence is currently dispersed in small case series and single case reports. In this paper, we briefly analyze conventional therapies for EP, before going on to critically evaluate the existing clinical evidence for the role of current biological drugs, namely infliximab, etanercept, adalimumab, and ustekinumab. Finally, we discuss the potential benefits that newer/developmental biological agents could bring to the management of EP. PMID:25752640

  3. Safety profiles and efficacy of infliximab therapy in Japanese patients with plaque psoriasis with or without psoriatic arthritis, pustular psoriasis or psoriatic erythroderma: Results from the prospective post-marketing surveillance.

    PubMed

    Torii, Hideshi; Terui, Tadashi; Matsukawa, Miyuki; Takesaki, Kazumi; Ohtsuki, Mamitaro; Nakagawa, Hidemi

    2016-07-01

    A large-scale prospective post-marketing surveillance was conducted to evaluate the safety and efficacy of infliximab in Japanese patients with plaque psoriasis, psoriatic arthritis, pustular psoriasis and psoriatic erythroderma. This study was conducted in all psoriasis patients treated with infliximab after its Japanese regulatory approval. Infliximab was administrated at 5 mg/kg at weeks 0, 2 and 6, and every 8 weeks thereafter. Patients were serially enrolled and observed for 6 months to evaluate the safety and efficacy. The safety and efficacy were evaluated in 764 and 746 patients, respectively. Incidences of any and serious adverse drug reactions were 22.51% and 6.94%, respectively, and those of any and serious infusion reactions were 6.15% and 1.31%, respectively, which were comparable with the results in the post-marketing surveillance with 5000 rheumatoid arthritis patients in Japan. Major adverse drug reactions during the follow-up period were infections (5.10%) including pneumonia, cellulitis and herpes zoster, however, no tuberculosis was observed. The safety profiles were equivalent, regardless of the psoriasis types. No new safety problems were identified. The response rates on global improvement and median improvement rate of Psoriasis Area and Severity Index in all patients were 88.0% and 85.0%, respectively. Of note, the efficacy was equivalent for each psoriasis type as well as for each body region. Infliximab was also effective in pustular psoriasis symptoms, joint symptoms and nail psoriasis, as well as improvement of quality of life. Infliximab was confirmed to be highly effective and well tolerated in treating refractory psoriasis, including pustular psoriasis and psoriatic erythroderma. PMID:26704926

  4. The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis

    PubMed Central

    Roubille, Camille; Richer, Vincent; Starnino, Tara; McCourt, Collette; McFarlane, Alexandra; Fleming, Patrick; Siu, Stephanie; Kraft, John; Lynde, Charles; Pope, Janet; Gulliver, Wayne; Keeling, Stephanie; Dutz, Jan; Bessette, Louis; Bissonnette, Robert; Haraoui, Boulos

    2015-01-01

    The objective of this systematic literature review was to determine the association between cardiovascular events (CVEs) and antirheumatic drugs in rheumatoid arthritis (RA) and psoriatic arthritis (PsA)/psoriasis (Pso). Systematic searches were performed of MEDLINE, EMBASE and Cochrane databases (1960 to December 2012) and proceedings from major relevant congresses (2010–2012) for controlled studies and randomised trials reporting confirmed CVEs in patients with RA or PsA/Pso treated with antirheumatic drugs. Random-effects meta-analyses were performed on extracted data. Out of 2630 references screened, 34 studies were included: 28 in RA and 6 in PsA/Pso. In RA, a reduced risk of all CVEs was reported with tumour necrosis factor inhibitors (relative risk (RR), 0.70; 95% CI 0.54 to 0.90; p=0.005) and methotrexate (RR, 0.72; 95% CI 0.57 to 0.91; p=0.007). Non-steroidal anti-inflammatory drugs (NSAIDs) increased the risk of all CVEs (RR, 1.18; 95% CI 1.01 to 1.38; p=0.04), which may have been specifically related to the effects of rofecoxib. Corticosteroids increased the risk of all CVEs (RR, 1.47; 95% CI 1.34 to 1.60; p<0.001). In PsA/Pso, systemic therapy decreased the risk of all CVEs (RR, 0.75; 95% CI 0.63 to 0.91; p=0.003). In RA, tumour necrosis factor inhibitors and methotrexate are associated with a decreased risk of all CVEs while corticosteroids and NSAIDs are associated with an increased risk. Targeting inflammation with tumour necrosis factor inhibitors or methotrexate may have positive cardiovascular effects in RA. In PsA/Pso, limited evidence suggests that systemic therapies are associated with a decrease in all CVE risk. PMID:25561362

  5. The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis.

    PubMed

    Roubille, Camille; Richer, Vincent; Starnino, Tara; McCourt, Collette; McFarlane, Alexandra; Fleming, Patrick; Siu, Stephanie; Kraft, John; Lynde, Charles; Pope, Janet; Gulliver, Wayne; Keeling, Stephanie; Dutz, Jan; Bessette, Louis; Bissonnette, Robert; Haraoui, Boulos

    2015-03-01

    The objective of this systematic literature review was to determine the association between cardiovascular events (CVEs) and antirheumatic drugs in rheumatoid arthritis (RA) and psoriatic arthritis (PsA)/psoriasis (Pso). Systematic searches were performed of MEDLINE, EMBASE and Cochrane databases (1960 to December 2012) and proceedings from major relevant congresses (2010-2012) for controlled studies and randomised trials reporting confirmed CVEs in patients with RA or PsA/Pso treated with antirheumatic drugs. Random-effects meta-analyses were performed on extracted data. Out of 2630 references screened, 34 studies were included: 28 in RA and 6 in PsA/Pso. In RA, a reduced risk of all CVEs was reported with tumour necrosis factor inhibitors (relative risk (RR), 0.70; 95% CI 0.54 to 0.90; p=0.005) and methotrexate (RR, 0.72; 95% CI 0.57 to 0.91; p=0.007). Non-steroidal anti-inflammatory drugs (NSAIDs) increased the risk of all CVEs (RR, 1.18; 95% CI 1.01 to 1.38; p=0.04), which may have been specifically related to the effects of rofecoxib. Corticosteroids increased the risk of all CVEs (RR, 1.47; 95% CI 1.34 to 1.60; p<0.001). In PsA/Pso, systemic therapy decreased the risk of all CVEs (RR, 0.75; 95% CI 0.63 to 0.91; p=0.003). In RA, tumour necrosis factor inhibitors and methotrexate are associated with a decreased risk of all CVEs while corticosteroids and NSAIDs are associated with an increased risk. Targeting inflammation with tumour necrosis factor inhibitors or methotrexate may have positive cardiovascular effects in RA. In PsA/Pso, limited evidence suggests that systemic therapies are associated with a decrease in all CVE risk. PMID:25561362

  6. Recent advances in phototherapy for psoriasis

    PubMed Central

    Nakamura, Mio; Farahnik, Benjamin; Bhutani, Tina

    2016-01-01

    Phototherapy involves repeated exposure of the skin to ultraviolet light to treat various inflammatory skin conditions such as psoriasis. Recent studies have identified specific immunologic effects of phototherapy that may underlie phototherapy efficacy. Furthermore, recent advancements have been made in developing safe and effective targeted phototherapy modalities for difficult-to-treat areas such as scalp psoriasis. Targeted phototherapy in the form of the excimer laser holds potential for more aggressive, effective treatment and long-lasting remission of psoriasis. Phototherapy is now also used successfully with biologic agents as combination therapy to treat recalcitrant psoriasis. Therefore, though one of the oldest therapeutic modalities for psoriasis, phototherapy remains a mainstay treatment with promise for further advancement. PMID:27499849

  7. Developing Shingles-Induced Koebner Phenomenon in a Patient With Psoriasis

    PubMed Central

    Zhao, Yu-Kun; Zhang, Yun-Qing; Wang, Fang; Wu, Hui-Hui; Luo, Ze-Yu; Luo, Di-Qing; Chen, Wen-Na

    2015-01-01

    Abstract Both shingles and psoriasis are common cutaneous diseases. About 25% of the psoriatic patients develop Koebner phenomenon (KP) after various injuries, and in rare instance, KP may occur at the site of healed or healing shingles. We report a 30-year-old man with 7-month history of scalp psoriasis who developed KP at the areas of developing shingles. Cutaneous examination revealed scaly erythematous papules and plaques located on the scalp and forehead, and groups of clustered erythematous papules with silver scales in the dermatome distributed on the right side of chest wall the prior herpes zoster lesions involved. After removal of the scales on the papules, underlying bleeding points were present. The lesions on chest had good response to anti-psoriatic therapies, as the lesions on scalp did. After a year of follow-up, recurrent psoriasis occurred, but the lesions were located only on the scalp, and the areas of prior occurrence of shingles, because of which we considered diagnosis of recurrent psoriasis rather than relapsing KP for the chest lesions. Not only the healing and healed shingles can trigger KP in psoriasis, but also the developing shingles can cause psoriatic KP at the site of herpes zoster lesions. PMID:26131802

  8. A gold nanoparticles-based colorimetric test to detect single nucleotide polymorphisms for improvement of personalized therapy of psoriasis

    NASA Astrophysics Data System (ADS)

    Marsella, Alessandra; Valentini, Paola; Tarantino, Paolo; Congedo, Maurizio; Pompa, Pier Paolo

    2016-04-01

    We report a simple, rapid and low-cost test, based on gold nanoparticles, for the naked-eye colorimetric detection of a signature of single nucleotide polymorphisms (SNPs) relevant for the personalized medicine of psoriasis patients. We validated the colorimetric assay on real-world DNA samples from a cohort of 30 psoriasis patients and we compared the results, in double-blind, with those obtained with two state-of-the-art instrumental techniques, namely reverse dot blotting and direct sequencing, finding 100% agreement. We demonstrated high accuracy, sensitivity and specificity of the colorimetric test that can be easily adapted for the genotypization of different SNPs, important for the pharmacogenomics of various diseases, and in other fields, such as food traceability and population structure analysis.

  9. The tumor necrosis factor receptor superfamily member 1B polymorphisms predict response to anti-TNF therapy in patients with autoimmune disease: A meta-analysis.

    PubMed

    Chen, Wenjuan; Xu, Hui; Wang, Xiuxiu; Gu, Junying; Xiong, Huizi; Shi, Yuling

    2015-09-01

    Numerous published data on the tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) gene polymorphisms are shown to be associated with response or non-response to anti-TNF therapy in autoimmune diseases such as rheumatoid arthritis (RA), psoriasis and Crohn's Disease (CD). The aim of this study is to investigate whether the TNFRSF1B rs1061622 T/G or TNFRSF1A A/G rs767455 polymorphisms can predict the response to anti-TNF-based therapy in patients with autoimmune diseases. We conducted a meta-analysis of studies on the association between TNFRSF1B rs1061622 T/G polymorphism or TNFRSF1A A/G rs767455 polymorphism and non-responsiveness to anti-TNF therapy in autoimmune diseases. A total of 8 studies involving 929 subjects for TNFRSF1B rs1061622 and 564 subjects for TNFRSF1A rs767455 were finally considered. These studies consisted of seven studies on the TNFRSF1B polymorphism and four studies on the TNFRSF1A polymorphism. Meta-analysis showed significant association between the TNFRSF1B rs1061622 allele and non-responders to anti-TNF therapy [T/G odds ratio (OR) 0.72, 95% confidence interval (CI) 0.57-0.93, p=0.01]. Stratification by disease type indicated an association between the TNFRSF1B rs1061622 allele and non-responders to TNF antagonist in RA (T/G OR 0.69, 95% CI 0.48-0.99, p<0.05) and psoriasis (T/G OR 0.39, 95% CI 0.23-0.67, p<0.001), but not in CD (T/G OR 1.14, 95% CI 0.57-0.93, p=0.57). And there was no association between TNFRSF1A rs767455 genotype and non-responders to the anti-TNF therapy (A/G OR 0.93, 95% CI 0.70-1.23, p=0.59). This meta-analysis demonstrates that TNFRSF1B T allele carriers show a better response to anti-TNF therapy, and individuals carrying TNFRSF1A A allele have no relationship with the response to anti-TNF therapy for autoimmune diseases. The genotyping of this polymorphism could help to optimize the treatment by identifying patients with a likely poor response to biological drugs. PMID:26071216

  10. Cell Targeting in Anti-Cancer Gene Therapy

    PubMed Central

    Lila, Mohd Azmi Mohd; Siew, John Shia Kwong; Zakaria, Hayati; Saad, Suria Mohd; Ni, Lim Shen; Abdullah, Jafri Malin

    2004-01-01

    Gene therapy is a promising approach towards cancer treatment. The main aim of the therapy is to destroy cancer cells, usually by apoptotic mechanisms, and preserving others. However, its application has been hindered by many factors including poor cellular uptake, non-specific cell targeting and undesirable interferences with other genes or gene products. A variety of strategies exist to improve cellular uptake efficiency of gene-based therapies. This paper highlights advancements in gene therapy research and its application in relation to anti-cancer treatment. PMID:22977356

  11. Anti-coagulant therapy with dabigatran for cystic fibrosis patients.

    PubMed

    Bansal, Manvi; Ren, Clement L

    2016-08-01

    Patients with cystic fibrosis (CF) are at increased risk of venous thromboembolism, especially in association with central venous catheter use. Coumarin drugs and low molecular weight heparin are frequently used for anti-coagulant therapy, but are more challenging to administer in CF patients. Dabigatran, an oral thrombin antagonist, is an alternative anti-coagulant medication, but its use in CF has not been reported. We describe our experience in successfully using dabigatran for long-term anti-coagulation therapy in two CF patients. Our experience suggests that dabigatran can serve as an option for anticoagulation therapy in CF. Pediatr Pulmonol. 2016;51:E29-E30. © 2016 Wiley Periodicals, Inc. PMID:27128852

  12. Adalimumab (TNFα Inhibitor) Therapy Exacerbates IgA Glomerulonephritis Acute Renal Injury and Induces Lupus Autoantibodies in a Psoriasis Patient

    PubMed Central

    Wei, S. S.; Sinniah, R.

    2013-01-01

    Adalimumab (Humira) is a tumour necrosis factor α (TNFα) inhibitor that is approved for the treatment of rheumatoid arthritis, psoriasis, psoriatic arthritis, Crohn's disease, ankylosing spondylitis, and juvenile idiopathic arthritis (Sullivan and Preda (2009), Klinkhoff (2004), and Medicare Australia). Use of TNFα inhibitors is associated with the induction of autoimmunity (systemic lupus erythematosus, vasculitis, and sarcoidosis or sarcoid-like granulomas) (Ramos-Casals et al. (2010)). We report a patient with extensive psoriasis presenting with renal failure and seropositive lupus markers without classical lupus nephritis after 18 months treatment with adalimumab. He has renal biopsy proven IgA nephritis instead. Renal biopsy is the key diagnostic tool in patients presenting with adalimumab induced nephritis and renal failure. He made a remarkable recovery after adalimumab cessation and steroid treatment. To our knowledge, this is a unique case of a psoriasis patient presenting with seropositive lupus markers without classical lupus nephritis renal failure and had renal biopsy proven IgA glomerulonephritis after receiving adalimumab. PMID:24558628

  13. Autoimmune disease: A role for new anti-viral therapies?

    PubMed

    Dreyfus, David H

    2011-12-01

    Many chronic human diseases may have an underlying autoimmune mechanism. In this review, the author presents a case of autoimmune CIU (chronic idiopathic urticaria) in stable remission after therapy with a retroviral integrase inhibitor, raltegravir (Isentress). Previous reports located using the search terms "autoimmunity" and "anti-viral" and related topics in the pubmed data-base are reviewed suggesting that novel anti-viral agents such as retroviral integrase inhibitors, gene silencing therapies and eventually vaccines may provide new options for anti-viral therapy of autoimmune diseases. Cited epidemiologic and experimental evidence suggests that increased replication of epigenomic viral pathogens such as Epstein-Barr Virus (EBV) in chronic human autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus Erythematosus (SLE), and multiple sclerosis (MS) may activate endogenous human retroviruses (HERV) as a pathologic mechanism. Memory B cells are the reservoir of infection of EBV and also express endogenous retroviruses, thus depletion of memory b-lymphocytes by monoclonal antibodies (Rituximab) may have therapeutic anti-viral effects in addition to effects on B-lymphocyte presentation of both EBV and HERV superantigens. Other novel anti-viral therapies of chronic autoimmune diseases, such as retroviral integrase inhibitors, could be effective, although not without risk. PMID:21871974

  14. Anti-vascular therapies in ovarian cancer: moving beyond anti-VEGF approaches

    PubMed Central

    Choi, Hyun-Jin; Pena, Guillermo N. Armaiz; Pradeep, Sunila; Cho, Min Soon; Coleman, Robert L.; Sood, Anil K.

    2014-01-01

    Resistance to chemotherapy is among the most important issues in the management of ovarian cancer. Unlike cancer cells, which are heterogeneous as a result of remarkable genetic instability, stromal cells are considered relatively homogeneous. Thus, targeting the tumor microenvironment is an attractive approach for cancer therapy. Arguably, anti-vascular endothelial growth factor (anti-VEGF) therapies hold great promise, but their efficacy has been modest, likely owing to redundant and complementary angiogenic pathways. Components of platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and other pathways may compensate for VEGF blockade and allow angiogenesis to occur despite anti-VEGF treatment. In addition, hypoxia induced by antiangiogenesis therapy modifies signaling pathways in tumor and stromal cells, which induces resistance to therapy. Because of tumor cell heterogeneity and angiogenic pathway redundancy, combining cytotoxic and targeted therapies or combining therapies targeting different pathways can potentially overcome resistance. Although targeted therapy is showing promise, much more work is needed to maximize its impact, including the discovery of new targets and identification of individuals most likely to benefit from such therapies. PMID:25544368

  15. [Systemic treatments for psoriasis and psoriatic arthritis].

    PubMed

    Philipp, S; Kokolakis, G; Sabat, R

    2016-06-01

    Psoriasis is one of the most common chronic dermatoses. More than 25 % of the affected individuals require effective systemic treatment because of severe symptoms and/or the significantly restricted quality of life. Thanks to intensive research and successful cooperation between academia and the pharmaceutical industry, the options for treating psoriasis have dramatically increased in recent years. Especially targeted therapies give us the opportunity for personalized regimen. This review describes the spectrum of the systemic treatments for psoriasis and psoriatic arthritis and discusses the efficacy, safety, and particular features of the individual substances. PMID:27240668

  16. Tuberculosis infection versus anti-tumor necrosis factor therapy: screening challenges in psoriatic patients

    PubMed Central

    Solovan, Caius; Chiticariu, Elena; Timofte, Adelina; Stoia-Djeska, Irina

    2012-01-01

    Objectives The aim of this study was to analyze the performance of the tuberculin skin test (TST) for screening and monitoring patients treated with anti-tumor necrosis factor agents, in a high-incidence area. Methods A 3-year retrospective study was carried out on 268 subjects. The study included 68 patients with moderate-to-severe psoriasis, screened for latent tuberculosis infection (LTBI) and subjects without psoriasis (100 adults and 100 children) with close contact with infected individuals. Results Positive tuberculin skin test (TST) results (induration >5 mm) were observed in 70.5% (48/68) of patients with psoriasis, higher than those observed in subjects with suspicion of tuberculosis or with close contact with infected individuals: 51% (51/100) in the adult group and 30% (30/100) in the children group. Conclusions These results show that the prevalence of LTBI evaluated with the TST in the psoriatic group is higher than in subjects without psoriasis. Limitation The positive reactions were not confirmed by other verification methods.

  17. Getting under the Skin: Report from the International Psoriasis Council Workshop on the Role of Stress in Psoriasis.

    PubMed

    Schwartz, Julia; Evers, Andrea W M; Bundy, Christine; Kimball, Alexandra B

    2016-01-01

    Psoriasis is a chronic inflammatory skin condition with significant physical and psychosocial comorbidity. A workshop of leading experts in dermatology and psychology with the purpose of better understanding the current role of psychological comorbidities in psoriasis was held by the International Psoriasis Council in November 2013. The role of stress reactivity with a focus on the hypothalamic-pituitary-adrenal axis was emphasized. While cognitive behavioral therapy remains the most extensively studied and successful treatment strategy in patients with psoriasis and various psychological comorbidities, new and innovative interventions such as online-based therapies have recently emerged. Strategies and recommendations toward approaching psychological comorbidities are discussed. PMID:26869982

  18. Imatinib may be ABL to improve anti-angiogenic therapy

    PubMed Central

    Raimondi, Claudio; Fantin, Alessandro; Ruhrberg, Christiana

    2015-01-01

    We recently reported that neuropilin 1 (NRP1) drives angiogenesis by promoting extracellular matrix signaling in endothelial cells via ABL1 kinase. Imatinib targets this pathway in pathological angiogenesis and may provide a novel opportunity for anti-angiogenic therapy of age-related macular degeneration, proliferative diabetic retinopathy, or solid tumor growth. PMID:27308396

  19. Photodynamic therapy and anti-tumour immunity

    PubMed Central

    Castano, Ana P.; Mroz, Pawel; Hamblin, Michael R.

    2010-01-01

    Photodynamic therapy (PDT) uses non-toxic photosensitizers and harmless visible light in combination with oxygen to produce cytotoxic reactive oxygen species that kill malignant cells by apoptosis and/or necrosis, shut down the tumour microvasculature and stimulate the host immune system. In contrast to surgery, radiotherapy and chemotherapy that are mostly immunosuppressive, PDT causes acute inflammation, expression of heat-shock proteins, invasion and infiltration of the tumour by leukocytes, and might increase the presentation of tumour-derived antigens to T cells. PMID:16794636

  20. [Anti-angiogenesis and molecular targeted therapies].

    PubMed

    Miyanaga, Akihiko; Gemma, Akihiko

    2015-08-01

    Tumor angiogenesis contributes to the development of tumor progression. Several vascular endothelial growth factor(VEGF)-targeted agents, administered either as single agents or in combination with chemotherapy, have been shown to benefit patients with advanced-stage malignancies. In particular, bevacizumab is a humanized monoclonal antibody that specifically targets VEGF, inhibiting angiogenesis, thereby impeding tumor growth and survival. It is also possible that combined VEGF and the epidermal growth factor (EGFR) pathway blockade could further enhance antitumor efficacy and help prevent resistance to therapy. Preclinical and clinical studies have shown new various molecular targets and the functional characteristics of tumor angiogenesis, which may provide strategies for improving the therapeutic benefit. PMID:26281687

  1. Targeting Phosphodiesterases in Anti-platelet Therapy

    PubMed Central

    Rondina, Matthew T.; Weyrich, Andrew S.

    2013-01-01

    There are two primary modes of platelet inhibition: blockade of membrane receptors or neutralization of intracellular pathways. Both means of inhibition have proven benefits in the prevention and resolution of atherothrombotic events. With regard to intracellular inhibition, phosphodiesterases (PDEs) are fundamental for platelet function. Platelets possess several PDEs (PDE2, PDE3 and PDE5) that catalyze the hydrolysis of cyclic adenosine 3′-5′-monophosphate (cAMP) and cyclic guanosine 3′-5′-monophosphate (cGMP), thereby limiting the levels of intracellular nucleotides. PDE inhibitors, such as cilostazol and dipyridamole, dampen platelet function by increasing cAMP and cGMP levels. This review focuses on the roles of PDE inhibitors in modulating platelet function, with particular attention paid to drugs that have anti-platelet clinical indications. PMID:22918733

  2. New-onset psoriasis in a maintenance hemodialysis patient.

    PubMed

    Triga, Konstantina; Dousdampanis, Periklis; Aggelakou-Vaitis, Stamatina; Gellner, Karen

    2012-01-01

    New-onset psoriasis is extremely rare in hemodialysis (HD) patients, and several trials of dialysis therapies (HD and peritoneal dialysis) in psoriasis have indicated remarkable improvement in skin lesions and well-being even in patients without renal impairment. We describe a patient who developed severe psoriasis despite undergoing chronic maintenance hemodialysis for 5 years and was treated successfully with oral cyclosporin A. PMID:22098821

  3. Antibiotic and Anti-Inflammatory Therapies for Cystic Fibrosis

    PubMed Central

    Chmiel, James F.; Konstan, Michael W.; Elborn, J. Stuart

    2013-01-01

    Cystic fibrosis (CF) lung disease is characterized by chronic bacterial infection and an unremitting inflammatory response, which are responsible for most of CF morbidity and mortality. The median expected survival has increased from <6 mo in 1940 to >38 yr now. This dramatic improvement, although not great enough, is due to the development of therapies directed at secondary disease pathologies, especially antibiotics. The importance of developing treatments directed against the vigorous inflammatory response was realized in the 1990s. New therapies directed toward the basic defect are now visible on the horizon. However, the impact of these drugs on downstream pathological consequences is unknown. It is likely that antibiotics and anti-inflammatory drugs will remain an important part of the maintenance regimen for CF in the foreseeable future. Current and future antibiotic and anti-inflammatory therapies for CF are reviewed. PMID:23880054

  4. Antibiotic and anti-inflammatory therapies for cystic fibrosis.

    PubMed

    Chmiel, James F; Konstan, Michael W; Elborn, J Stuart

    2013-10-01

    Cystic fibrosis (CF) lung disease is characterized by chronic bacterial infection and an unremitting inflammatory response, which are responsible for most of CF morbidity and mortality. The median expected survival has increased from <6 mo in 1940 to >38 yr now. This dramatic improvement, although not great enough, is due to the development of therapies directed at secondary disease pathologies, especially antibiotics. The importance of developing treatments directed against the vigorous inflammatory response was realized in the 1990s. New therapies directed toward the basic defect are now visible on the horizon. However, the impact of these drugs on downstream pathological consequences is unknown. It is likely that antibiotics and anti-inflammatory drugs will remain an important part of the maintenance regimen for CF in the foreseeable future. Current and future antibiotic and anti-inflammatory therapies for CF are reviewed. PMID:23880054

  5. Genes and Psoriasis

    MedlinePlus

    ... Psoriatic Arthritis Info Kit Resources Community icon: Link text: Post your questions in our online community and ... psoriasis and psoriatic arthritis. Talk Psoriasis icon: Link text: Contact our Patient Navigators for free and confidential ...

  6. Psoriasis (For Parents)

    MedlinePlus

    ... accompanied by fever, chills, severe itching, and fatigue. Inverse psoriasis. This causes smooth, raw-looking patches of ... a healthy weight. This decreases the risk of inverse psoriasis. Remind your child to keep skin clean ...

  7. National Psoriasis Foundation

    MedlinePlus

    ... Psoriatic Arthritis Info Kit Resources Community icon: Link text: Post your questions in our online community and ... psoriasis and psoriatic arthritis. Talk Psoriasis icon: Link text: Contact our Patient Navigators for free and confidential ...

  8. Anti-idiotype antibody vaccine therapy for cancer.

    PubMed

    Bhattacharya-Chatterjee, Malaya; Chatterjee, Sunil K; Foon, Kenneth A

    2002-12-01

    The use of anti-idiotype (Id) antibodies as vaccines to stimulate antitumour immunity is one of several promising immunologic approaches to the therapy of cancer. Extensive studies in animal tumour models have demonstrated the efficacy of anti-Id vaccines in preventing tumour growth and curing mice with established tumours. A number of monoclonal anti-Id antibodies that mimic distinct human tumour-associated antigens (TAAs) have been developed and tested in the clinic, and demonstrate encouraging results. In general, the antigen mimicry by anti-Id antibodies has reflected structural homology in the majority of the cases, and amino acid sequence homology in a few of them. The greatest challenge of immunotherapy by means of anti-Id vaccines is to identify the optimal anti-Id antibody that will function as a true surrogate antigen for a TAA system, and ideally will generate both humoral and cellular immune responses. Although several clinical studies have shown enhanced survival of patients receiving anti-Id vaccines, the efficacy of these vaccines will depend on the results of several randomised Phase III clinical trials that are currently planned or ongoing. PMID:12517266

  9. Summary of the Dutch S3-guidelines on the treatment of psoriasis 2011. Dutch Society of Dermatology and Venereology.

    PubMed

    Zweegers, J; de Jong, E M G J; Nijsten, T E C; de Bes, J; te Booij, M; Borgonjen, R J; van Cranenburgh, O D; van Deutekom, H; van Everdingen, J J E; de Groot, M; Van Hees, C L M; Hulshuizen, H; Koek, M B G; de Korte, W J A; de Korte, J; Lecluse, L L A; Pasch, M C; Poblete-Gutiérrez, P A; Prens, E P; Seyger, M M B; Thio, H B; Torcque, L A; de Vries, A C Q; van de Kerkhof, P C M; Spuls, Ph I

    2014-03-01

    This document provides a summary of the Dutch S3-guidelines on the treatment of psoriasis. These guidelines were finalized in December 2011 and contain unique chapters on the treatment of psoriasis of the face and flexures, childhood psoriasis as well as the patient's perspective on treatment. They also cover the topical treatment of psoriasis, photo(chemo)therapy, conventional systemic therapy and biological therapy. PMID:24656281

  10. Advances in Anti-IgE Therapy

    PubMed Central

    Yalcin, Arzu Didem

    2015-01-01

    Omalizumab depletes free IgE in the blood and interstitial space and inhibits IgE binding to FcεRI on basophils, mast cells, and dendritic cells. We stopped omalizumab treatment after four years. Recurrences of urticaria symptoms were found to be higher in patients with chronic urticaria than recurrences of asthmatic symptoms in severe persistent asthma patients. For the very first time, we used omalizumab in symptomatic therapy of recurrent laryngeal oedema and urticaria attacks in a patient with postoperative pulmonary carcinoid tumor for eight months. During the four years of follow-up, no recurrence was noted in pulmonary carcinoid tumor. Control PET CT results revealed normal findings. After omalizumab treatment, laryngeal oedema and urticaria symptoms were decreased. The most common adverse reaction from omalizumab is injection site induration, injection site itching, injection site pain, and bruising but the package insert contains warnings regarding parasitic infections. While there are no reports of fatal anaphylaxis as a result of omalizumab, some cases have been serious and potentially life-threatening. Therefore, the FDA requires that people receiving omalizumab be monitored in the physician's office for a period of time after their injections. PMID:26075226

  11. Anti-platelet therapy in small animal medicine.

    PubMed

    Thomason, J; Lunsford, K; Mackin, A

    2016-08-01

    Thromboembolism is a significant complication in many commonly encountered diseases, and can be a devastating sequel to otherwise treatable conditions. Platelets play an essential role in the hemostatic process and, consequently, are associated with thrombus formation. Platelets adhere to denuded vascular subendothelium, recruit additional platelets and cells, aggregate, and provide the catalytic surface for thrombin production and fibrin formation. Therapy to prevent unwanted thrombus formation and thromboembolic crises is essential in the management of hypercoagulable patients. Unfortunately, many of the medications used in veterinary medicine that inhibit or modulate coagulation factors, such as the heparins, are cost prohibitive, only effective when administered by injection or require frequent drug monitoring, and are therefore poor choices for long term at home therapy. While the role of the platelet in pathologic thrombus formation is not fully understood, veterinarians often resort to anti-platelet therapy in the management of patients at risk for thromboembolic complications, because many anti-platelet medications are inexpensive, require minimal drug monitoring, and can be given orally. The aim of this review is to discuss the anti-platelet therapies that are currently being used or being considered for use to inhibit platelet function and reduce thromboembolic complications in hypercoagulable dogs and cats. PMID:26969126

  12. Implantable synthetic cytokine converter cells with AND-gate logic treat experimental psoriasis.

    PubMed

    Schukur, Lina; Geering, Barbara; Charpin-El Hamri, Ghislaine; Fussenegger, Martin

    2015-12-16

    Psoriasis is a chronic inflammatory skin disease characterized by a relapsing-remitting disease course and correlated with increased expression of proinflammatory cytokines, such as tumor necrosis factor (TNF) and interleukin 22 (IL22). Psoriasis is hard to treat because of the unpredictable and asymptomatic flare-up, which limits handling of skin lesions to symptomatic treatment. Synthetic biology-based gene circuits are uniquely suited for the treatment of diseases with complex dynamics, such as psoriasis, because they can autonomously couple the detection of disease biomarkers with the production of therapeutic proteins. We designed a mammalian cell synthetic cytokine converter that quantifies psoriasis-associated TNF and IL22 levels using serially linked receptor-based synthetic signaling cascades, processes the levels of these proinflammatory cytokines with AND-gate logic, and triggers the corresponding expression of therapeutic levels of the anti-inflammatory/psoriatic cytokines IL4 and IL10, which have been shown to be immunomodulatory in patients. Implants of microencapsulated cytokine converter transgenic designer cells were insensitive to simulated bacterial and viral infections as well as psoriatic-unrelated inflammation. The designer cells specifically prevented the onset of psoriatic flares, stopped acute psoriasis, improved psoriatic skin lesions and restored normal skin-tissue morphology in mice. The antipsoriatic designer cells were equally responsive to blood samples from psoriasis patients, suggesting that the synthetic cytokine converter captures the clinically relevant cytokine range. Implanted designer cells that dynamically interface with the patient's metabolism by detecting specific disease metabolites or biomarkers, processing their blood levels with synthetic circuits in real time, and coordinating immediate production and systemic delivery of protein therapeutics may advance personalized gene- and cell-based therapies. PMID:26676608

  13. Lasers for the treatment of psoriasis

    NASA Astrophysics Data System (ADS)

    Piruzian, A.; Korsunskaya, I.; Goldenkova, I.; Hertsen, A.; Sarkisova, M.; Egorenkova, L.

    2005-08-01

    Psoriasis is a chronic, genetically-determined disease, characterized by an immuno-mediated pathogenesis. Treatment of psoriasis is often complicated and remains a challenge. Along with the many new immunomodulatory approaches, various laser systems have been employed for chronic plaque psoriasis treatment. Recently, it has been demonstrated that the light produced by xenon-chloride excimers (generated by sophisticated devices with peak emission of 308 nm) is effective in the treatment of several psoriasis forms. We treated patients, ranging in age from 35 to 55 years, affected by plaque-type psoriasis vulgaris with monochromatic excimer light (MEL). We used MEL in a complex with basic treatment. Therapy was administered three times a week. At the end of the 3th week of treatment all patients showed an improvement, as evidenced by flattening of plaques, decreased scaling and erythema, and decreased vesicle and pustule formation. Unwanted side effects such as pain, blistering was not observed. Minimal erythema and a hyperpigmentation were noted in some patients. It was concluded that the MEL therapy may be a valuable option for treatment of plaque-type psoriasis vulgaris in shorter time compare with traditional NB UVB, with exposure to lower cumulative doses

  14. Psoriasis induced by thalidomide in a patient with multiple myeloma

    PubMed Central

    Ferrazzi, Anna; Zambello, Renato; Russo, Irene; Alaibac, Mauro

    2014-01-01

    A 54-year-old woman developed psoriasis on the plantar surface of her feet after 2 weeks of thalidomide 100 mg daily for the treatment of multiple IgG myeloma. She did not have any previous history of psoriasis. Thalidomide was immediately stopped and topical treatment with calcipotriol ointment and β-methasone valerate was started. Psoriasis disappeared completely after 2 weeks of topical therapy. This is the first case of de novo psoriasis in a patient with multiple myeloma under treatment with thalidomide. Our observation provides further evidence of the potential paradoxical effect of thalidomide on tumour necrosis factor-α production. PMID:24973347

  15. Anti-angiogenesis in cancer therapy: Hercules and hydra.

    PubMed

    Bellou, S; Pentheroudakis, G; Murphy, C; Fotsis, T

    2013-09-28

    Solid tumours initiate angiogenesis to support their growth by producing growth factors such as VEGF. Depriving the tumour of the excessive vessels that support its growth became the target for developing anti-angiogenic agents that could provide, in combination with chemotherapy, improved anti-cancer treatment. Naturally most agents targeted VEGF and its signalling cascades. Almost 10 years have lapsed since the first anti-angiogenic drug approved by the FDA in 2004 (a humanized antibody inhibiting VEGF-A) and several other agents followed afterwards. There is sufficient accumulated experience to conclude that the clinical results of anti-angiogenic therapy are very modest resulting in moderate improvement in overall survival. Moreover, the clinical outcome is associated with the development of resistance to the anti-angiogenic agent and the increased risk of invasion and metastasis. The initial expectations are, as yet, unfilled, and the entire concept and strategy of the anti-angiogenic intervention in cancer requires re-evaluation. In the present Mini Review we discuss these issues emphasising the underlying molecular mechanisms. PMID:23707856

  16. Psoriasis Patients' Knowledge about the Disease and Treatments

    PubMed Central

    Wahl, Astrid Klopstad; Moum, Torbjørn; Larsen, Marie Hamilton; Krogstad, Anne Lene

    2013-01-01

    Patients' knowledge about psoriasis and its treatment has been randomly studied previously. The aim of the study is to investigate patients' knowledge about psoriasis in relation to undergoing patient education in the context of climate therapy (CT). The psoriasis knowledge questionnaire (PKQ) was used in a follow-up pre–post study design of Norwegian patients with psoriasis at the age of 20 years and older undergoing CT at Gran Canaria (Spain). Patients completed the PKQ and provided selected demographic, clinical and health information before (T1), immediately after (T2), and 3 months after (T3) CT. Disease severity was assessed using the psoriasis area and severity index (PASI). 254 psoriasis patients were included (74%). The PKQ score improved significantly from T1 to T2 and T3 (P < 0.001 for both comparisons). Although patient's knowledge improved, further research should use gold standard designs (experiments) to study the effects of educational interventions in different contexts. PMID:23864852

  17. [Anti-angiogenic therapies: from theory to practice].

    PubMed

    Bidart, Marie; Berger, François; Pelletier, Laurent

    2013-01-01

    During recent years clear progress has been made in support of tumor pathology. However, the treatment of metastatic disease is now a real therapeutic challenge. Among the new therapeutic strategies, blocking angiogenesis has been the subject of numerous clinical trials. However, if this approach was validated in 2004 by the approval of the first humanized anti-VEGF antibody (bevacizumab or Avastin(®), Roche, 2004), the pre-clinical and clinical studies conducted in the last 5 years have moderated the enthusiasm that these therapies had led in the early 2000s. In November 2011, the US Food and drug administration (FDA) revoke the agency's approval of the breast cancer indication for Avastin(®) because of benefit-risk balance appears negative. This review describes successively the mechanisms of action of antiangiogenic agents, the main anti-angiogenic drugs and the theoretical advantages and practical limitations of these therapies. PMID:24113438

  18. Anti-tumor necrosis factor-α therapy in uveitis.

    PubMed

    Cordero-Coma, Miguel; Sobrin, Lucia

    2015-01-01

    Since the first reported use in 2001 of an anti-tumor necrosis factor-alpha (TNF-α) agent, infliximab, for the treatment of uveitis, several new anti-TNF-α agents have emerged for the treatment of refractory noninfectious uveitides, although their use remains off-label in the US. These agents have demonstrated remarkable clinical antiinflammatory efficacy and a potential immunoregulatory role in selected uveitis patients, but it is currently unclear whether they can modify the natural history of disease. We review the rationale and clinical indications for this therapy, the differences between agents, how to manage dosing and intervals, and how to screen for and identify potential side effects. We also present a summary of the science behind the use of anti-TNF-α agents in ocular inflammation and the evidence for their efficacy. PMID:26164735

  19. Defining response to anti-VEGF therapies in neovascular AMD

    PubMed Central

    Amoaku, W M; Chakravarthy, U; Gale, R; Gavin, M; Ghanchi, F; Gibson, J; Harding, S; Johnston, R L; Kelly, S; Lotery, A; Mahmood, S; Menon, G; Sivaprasad, S; Talks, J; Tufail, A; Yang, Y

    2015-01-01

    The introduction of anti-vascular endothelial growth factor (anti-VEGF) has made significant impact on the reduction of the visual loss due to neovascular age-related macular degeneration (n-AMD). There are significant inter-individual differences in response to an anti-VEGF agent, made more complex by the availability of multiple anti-VEGF agents with different molecular configurations. The response to anti-VEGF therapy have been found to be dependent on a variety of factors including patient's age, lesion characteristics, lesion duration, baseline visual acuity (VA) and the presence of particular genotype risk alleles. Furthermore, a proportion of eyes with n-AMD show a decline in acuity or morphology, despite therapy or require very frequent re-treatment. There is currently no consensus as to how to classify optimal response, or lack of it, with these therapies. There is, in particular, confusion over terms such as ‘responder status' after treatment for n-AMD, ‘tachyphylaxis' and ‘recalcitrant' n-AMD. This document aims to provide a consensus on definition/categorisation of the response of n-AMD to anti-VEGF therapies and on the time points at which response to treatment should be determined. Primary response is best determined at 1 month following the last initiation dose, while maintained treatment (secondary) response is determined any time after the 4th visit. In a particular eye, secondary responses do not mirror and cannot be predicted from that in the primary phase. Morphological and functional responses to anti-VEGF treatments, do not necessarily correlate, and may be dissociated in an individual eye. Furthermore, there is a ceiling effect that can negate the currently used functional metrics such as >5 letters improvement when the baseline VA is good (ETDRS>70 letters). It is therefore important to use a combination of both the parameters in determining the response.The following are proposed definitions: optimal (good) response is defined as when

  20. Severe Nail Fold Psoriasis Extending from Nail Psoriasis Resolved with Ustekinumab: Suggestion of a Cytokine Overflow Theory in the Nail Unit

    PubMed Central

    Byun, Sang Young; Kim, Bo Ri; Choi, Jae Woo

    2016-01-01

    Because nail psoriasis is difficult to treat, therapy with many biological drugs has been attempted. Ustekinumab is approved for chronic plaque psoriasis and psoriatic arthritis (PsA), with some trials reporting nail improvement using this agent. A 51-year-old man with severe chronic plaque psoriasis had severe involvement of all fingernails and toenails, with accompanying nail fold psoriasis. He also had PsA of the small joints of the fingers. Despite multiple conventional therapies, the nail lesions did not improve, and his nail psoriasis severity index score was 97. After a fourth ustekinumab injection, most of the fingernail psoriasis was resolved, and only hyperkeratosis remained on both large toenails. Because the nail plate, nail fold, and small joints of the fingers are closely apposed structures within a small area, cytokines produced from the nail units overflow to the nail fold and small joints and can induce nail fold psoriasis and PsA. PMID:26848225

  1. Psoriatic alopecia/alopecia areata-like reactions secondary to anti-tumor necrosis factor-α therapy: a novel cause of noncicatricial alopecia.

    PubMed

    Doyle, Leona A; Sperling, Leonard C; Baksh, Shashi; Lackey, Jeffrey; Thomas, Brian; Vleugels, Ruth Ann; Qureshi, Abrar A; Velazquez, Elsa F

    2011-04-01

    With the increasing use of anti-tumor necrosis factor α (anti-TNF) biologic drugs to treat autoimmune diseases, an expanding array of adverse reactions is emerging. Anti-TNF drug-induced alopecia is a less well-known side effect of this class of drugs. The aim of this study was to define the clinical and histopathological features of alopecia arising in the setting of anti-TNF therapy. Clinical and histopathological features of 3 patients who developed scalp alopecia during anti-TNF treatment were examined. Two of the 3 patients also developed psoriasiform lesions outside the scalp, and biopsies from both scalp and nonscalp sites were reviewed. Clinically, each patient had large scaly patches associated with the scalp alopecia. All scalp biopsies revealed psoriasiform epidermal features and alopecia areata-like dermal changes. Epidermal changes included acanthosis and confluent parakeratosis with neutrophils and frank pustules. Dermal changes included markedly increased catagen/telogen and miniaturized hairs and peribulbar lymphocytic inflammation. Numerous plasma cells and eosinophils were present in all cases. Biopsies from the nonscalp lesions showed psoriasiform changes and prominent eosinophils and plasma cells. Two patients showed significant improvement of the alopecia with topical treatment only. In conclusion, anti-TNF therapy-related alopecia may closely mimic psoriatic alopecia and alopecia areata but can be histologically distinguished from alopecia areata by epidermal psoriasiform changes and dermal plasma cells and from primary psoriasis by the presence of plasma cells and eosinophils. A correct diagnosis can enable effective treatment and, in some cases, allow anti-TNF therapy to continue. PMID:21317611

  2. Autoimmune mechanisms in psoriasis.

    PubMed

    Reeves, W H

    1991-09-01

    Psoriasis is a chronic papulosquamous skin disorder affecting 1% to 3% of the general population. There is increasing evidence that immunologic mechanisms are involved in the pathogenesis of psoriasis, and that a link between psoriasis and autoimmunity may exist. A variety of autoantibodies has been observed in psoriasis including antinuclear antibodies, antibodies to small nuclear and cytoplasmic ribonucleoproteins, and antibodies to epidermal cells. UV light treatment of psoriasis may play a role in inducing these autoantibodies in some individuals. Recent evidence that activated T cells in psoriatic plaques may produce interferon-gamma leading to the appearance of ectopic class II major histocompatibility products on the surface of keratinocytes also supports the idea of a link between psoriasis and disordered immunoregulation. The immunologic abnormalities in psoriasis and the association of psoriasis with particular types of autoantibodies raise the possibility that a common etiology may underlie both psoriasis and autoimmunity in some patients, but the different responses of the two diseases to UV light treatment and certain pharmacological agents suggest that psoriasis may not have an autoimmune pathogenesis. PMID:1931571

  3. Immunotargeting in the management of psoriasis

    PubMed Central

    Kaffenberger, Benjamin H; Kaffenberger, Thomas M; Wong, Henry K

    2013-01-01

    The treatment of psoriasis has been revolutionized since the introduction of biologic therapies. Prior to their introduction, it was unclear if psoriasis was primarily a keratinocyte signaling dysfunction or an autoimmune T-cell mediated pathway. Nonspecific T-cell targeting treatments had been used with some success, but they were limited by a narrow therapeutic index. The nonspecific nature of these agents was fraught with side effects, and the efficacy of these treatments pales in comparison to current treatments. The initial biologic molecules, alefacept and efalizumab, were not specific for any T-cell driven pathway, and neither are currently available in the USA. The successors to these early therapies have shown high efficacy and low side effects in psoriasis and other autoimmune diseases through the specific targeting of tumor necrosis factor-alpha (TNF-α). Since the initial use of antitumor necrosis factor agents, a renaissance in our understanding of psoriasis has been underway, leading to the elucidation of the T-helper 17 (Th17) from the Th1 pathway. With each new treatment, the pathogenesis for psoriasis continues to be more defined, allowing for improved targeted therapies and the ability to achieve new milestones in efficacy.

  4. Use of amino terminal type III procollagen peptide (P3NP) assay in methotrexate therapy for psoriasis

    PubMed Central

    Khan, S; Subedi, D; Chowdhury, M M U

    2006-01-01

    Hepatic fibrosis continues to be a risk in patients receiving methotrexate for psoriasis. Measurement of amino terminal levels of type III procollagen (P3NP) has been advocated as an effective non‐invasive test for ongoing hepatic fibrogenesis that could avoid liver biopsies. An audit was conducted to assess the practice of P3NP monitoring using guidelines produced by Manchester and whether the agreed levels correlate with histological severity. Sixty five patients with 174 P3NP assays and 30 liver biopsies were reviewed between the years 1999 and 2003. Total number of patient‐methotrexate years was 278.9 and the mean cumulative dose of methotrexate received was 2000 (SD 1838) mg. A higher cumulative dose of methotrexate correlated significantly with high mean and maximum P3NP levels. Of the 30 liver biopsies, 26 (86.6%) showed normal histology or mild to moderate steatosis, three had focal fibrosis, and one had early cirrhosis. A median P3NP value of 5.8 μg/l or higher had a stronger correlation with histological severity. It is concluded that P3NP assay is a valuable adjunct to the clinical management of patients receiving long term methotrexate that can avoid or reduce unnecessary liver biopsies. PMID:16679477

  5. Decreased levels of metalloproteinase-9 and angiogenic factors in skin lesions of patients with psoriatic arthritis after therapy with anti-TNF-α

    PubMed Central

    Cordiali-Fei, Paola; Trento, Elisabetta; D'Agosto, Giovanna; Bordignon, Valentina; Mussi, Anna; Ardigò, Marco; Mastroianni, Antonio; Vento, Antonella; Solivetti, Francesco; Berardesca, Enzo; Ensoli, Fabrizio

    2006-01-01

    Background Inflammation represents an early and key event in the development of both the cutaneous psoriasis and psoriatic arthritis. Compelling evidences indicate that the production of TNF-α plays a central role in psoriasis by sustaining the inflammatory process in the skin as well as in the joints. Among the multiple effects produced by TNF-α on keratinocytes, the induction of matrix metalloproteinase-9 (MMP-9), a collagenase implicated in joint inflammatory arthritis which acts as an angiogenesis promoting factor, might represent a key mechanism in the pathogenesis of the disease. Aims of the present study were to investigate a) the role of MMP-9 in the development of psoriasis by assessing the presence of MMP-9 in lesional skin and in sera of psoriatic patients; b) the association of MMP-9 with the activity of the disease; c) the relationship between MMP-9 and TNF-α production. Methods Eleven psoriatic patients, clinically presenting joint symptoms associated to the cutaneous disease, were included in a therapeutic protocol based on the administration of anti-TNF-α monoclonal antibody (Infliximab). Sera and skin biopsies were collected before treatment and after 6 weeks of therapy. Tissues were kept in short term cultures and production soluble mediators such as TNF-α, MMP-9, MMP-2, VEGF and E-Selectin, which include angiogenic molecules associated to the development of plaque psoriasis, were measured in the culture supernatants by immunoenzymatic assays (ng/ml or pg/ml per mg of tissue). MMP-9 concentrations were also measured in the sera. The cutaneous activity of disease was evaluated by the Psoriasis Area and Severity Index (PASI). Results Clinical and laboratory assessment indicated that all but one patients had a significant improvement of the PASI score after three months of therapy. The clinical amelioration was associated to a significant decrease of MMP-9 (P = 0.017), TNF-α (P = 0.005) and E-selectin (P = 0.018) levels, spontaneously released

  6. Genetic Epidemiology of Psoriasis

    PubMed Central

    Gupta, Rashmi; Debbaneh, Maya G.; Liao, Wilson

    2014-01-01

    Psoriasis is a chronic, inflammatory, immune-mediated skin condition with a prevalence of 0-11.8% across the world. It is associated with a number of cardiovascular, metabolic, and autoimmune disease co-morbidities. Psoriasis is a multifactorial disorder, influenced by both genetic and environmental factors. Its genetic basis has long been established through twin studies and familial clustering. The association of psoriasis with the HLA-Cw6 allele has been shown in many studies. Recent genome-wide association studies have identified a large number of other genes associated with psoriasis. Many of these genes regulate the innate and adaptive immune system. These findings indicate that a dysregulated immune system may play a major role in the pathogenesis of psoriasis. In this article, we review the clinical and genetic epidemiology of psoriasis with a brief description of the pathogenesis of disease. PMID:25580373

  7. Biomarkers in Tumor Angiogenesis and Anti-Angiogenic Therapy

    PubMed Central

    Pircher, Andreas; Hilbe, Wolfgang; Heidegger, Isabel; Drevs, Joachim; Tichelli, André; Medinger, Michael

    2011-01-01

    Tumor angiogenesis has been identified to play a critical role in tumor growth and tumor progression, and is regulated by a balance of angiogenic and anti-angiogenic cytokines. Among them VEGF (vascular endothelial growth factor) and its signaling through its receptors are of crucial relevance. Inhibition of VEGF signaling by monoclonal antibodies or small molecules (kinase inhibitors) has already been successfully established for the treatment of different cancer entities and multiple new drugs are being tested in clinical trials. However not all patients are likely to respond to these therapies, but to date there are no reliable biomarkers available to predict therapy response. Many studies integrated biomarker programs in their study protocols, thus several potential biomarkers have been identified which are currently under clinical investigation in prospective randomized studies. This review intends to give an overview of the described potential biomarkers as well as different imaging techniques such as ultrasound and magnetic resonance imaging that can indicate benefit, resistance and toxicity to anti-angiogenic therapies. PMID:22072937

  8. Subpopulations of T lymphocytes in psoriasis patients and their changes during immunotherapy.

    PubMed

    Rubins, A Y; Merson, A G

    1987-12-01

    The content of T-lymphocytes and their basic subpopulations T-helpers and T-suppressors have been studied by means of monoclonal antibodies in the peripheral blood of 104 patients with different forms of psoriasis (56 patients with psoriasis vulgaris, 25 with exudative psoriasis, 10 with psoriasis arthropathica, and 13 with erythrodermic psoriasis). In all forms of psoriasis with a slight alteration in T-lymphocyte content a significant dysbalance of T-helpers and T-suppressors was found that brought about a decrease in the correlation ratio T-helpers/T-suppressors (T-helpers/T-suppressors in patients suffering from psoriasis vulgaris, 1.55 +/- 0.12; in those with exudative psoriasis, 1.24 +/- 0.16; with psoriasis arthropathica, 1.33 +/- 0.16; with erythrodermic psoriasis, 1.33 +/- 0.18; the control showed 1.82 +/- 0.08). The decrease in T-helpers/T-suppressors to 1.2 and lower that corresponded to a more severe clinical course of the disease was revealed in 27 patients having psoriasis vulgaris, in 13 with exudative psoriasis, in 7 with psoriasis arthropathica, and in 9 with erythrodermic psoriasis. The dysbalance in T-helpers/T-suppressors was due to a decrease in T-helpers and an increase in T-suppressors. To normalize T-helpers/T-suppressors, 27 psoriatics (20 with psoriasis vulgaris, 6 with exudative psoriasis, 1 with erythrodermic psoriasis) received immunomodulators Thymalinum and Natrii nucleinas in addition to antipsoriatic therapy, which resulted in an increase in T-helper/T-suppressor ratio, on the average up to 1.74 +/- 0.16 (prior to treatment T-helper/T-suppressor ratio in these patients was 1.0 +/- 0.14) and was followed by a favorable clinical course (shorter periods of skin rash regression, prolonged remissions).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2963042

  9. Vascular Mimicry: Concepts and Implications for Anti-Angiogenic Therapy

    PubMed Central

    Dunleavey, James M.; Dudley, Andrew C.

    2013-01-01

    As in normal tissues, solid tumors depend on vascular networks to supply blood, oxygen, and nutrients. Tumor blood vessels are formed by common processes of neovascularization for example endothelial sprouting. However, some tumors have alternative and unexpected mechanisms of neovascularization at their disposal. In a process termed “vascular mimicry,” tumors create their own, tumor cell-lined channels for fluid transport independent of typical modes of angiogenesis. These tumor cell-lined conduits may express endothelial-selective markers and anti-coagulant factors which allow for anastamosis with host endothelium. In this review, we explore the current status of vascular mimicry research, highlighting recent evidence which strengthens the hypothesis for this unusual ability of tumor cells. Furthermore, we address the theoretical possibility that vascular mimicry provides a mechanism whereby tumors could escape anti-angiogenic therapies. PMID:24729954

  10. Corneal Neovascularization: An Anti-VEGF Therapy Review

    PubMed Central

    Chang, Jin-Hong; Garg, Nitin K.; Lunde, Elisa; Han, Kyu-Yeon; Jain, Sandeep; Azar, Dimitri T.

    2013-01-01

    Corneal neovascularization is a serious condition that can lead to a profound decline in vision. The abnormal vessels block light, cause corneal scarring, compromise visual acuity, and may lead to inflammation and edema. Corneal neovascularization occurs when the balance between angiogenic and antiangiogenic factors is tipped toward angiogenic molecules. Vascular endothelial growth factor (VEGF), one of the most important mediators of angiogenesis, is upregulated during neovascularization. In fact, anti-VEGF agents have efficacy in the treatment of neovascular age-related macular degeneration, diabetic retinopathy, macular edema, neovascular glaucoma, and other neovascular diseases. These same agents have great potential for the treatment of corneal neovascularization. We review some of the most promising anti-VEGF therapies, including bevacizumab, VEGF trap, siRNA, and tyrosine kinase inhibitors. PMID:22898649

  11. Vertical Transmission of Histoplasmosis Associated With Anti-Tumor Necrosis Factor Therapy.

    PubMed

    Carlucci, James G; Halasa, Natasha; Creech, C Buddy; Dulek, Daniel E; Gómez-Duarte, Oscar G; Nelson, George E; Talbot, H Keipp; Scalise, Melissa L; Scott, Patricia L; Mahadevan, Uma; Beaulieu, Dawn B

    2016-06-01

    Therapeutics blocking the activity of tumor necrosis factor (anti-TNF) are a risk factor for invasive fungal infections; however, infectious risks to infants born to mothers receiving anti-TNF therapy are not well defined. We report a case of vertical transmission of disseminated histoplasmosis in a mother-infant pair exposed to anti-TNF therapy. PMID:27012275

  12. Anti-EGFR and anti-VEGF agents: important targeted therapies of colorectal liver metastases.

    PubMed

    Feng, Qing-Yang; Wei, Ye; Chen, Jing-Wen; Chang, Wen-Ju; Ye, Le-Chi; Zhu, De-Xiang; Xu, Jian-Min

    2014-04-21

    Colorectal liver metastasis (CLM) is common worldwide. Targeted therapies with monoclonal antibodies have been proven effective in numerous clinical trials, and are now becoming standards for patients with CLM. The development and application of anti-epidermal growth factor receptor (anti-EGFR) and anti-vascular endothelial growth factor (anti-VEGF) antibodies represents significant advances in the treatment of this disease. However, new findings continue to emerge casting doubt on the efficacy of this approach. The Kirsten rat sarcoma viral oncogene (KRAS) has been proven to be a crucial predictor of the success of anti-EGFR treatment in CLM. Whereas a recent study summarized several randomized controlled trials, and showed that patients with the KRAS G13D mutation significantly benefited from the addition of cetuximab in terms of progress-free survival (PFS, 4.0 mo vs 1.9 mo, HR = 0.51, P = 0.004) and overall survival (OS, 7.6 mo vs 5.7 mo, HR = 0.50, P = 0.005). Some other studies also reported that the KRAS G13D mutation might not be absolutely predictive of non-responsiveness to anti-EGFR therapy. At the same time, "new" RAS mutations, including mutations in neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) and exons 3 and 4 of KRAS, have been suggested to be predictors of a poor treatment response. This finding was first reported by the update of the PRIME trial. The update showed that for patients with non-mutated KRAS exon 2 but other RAS mutations, panitumumab-fluorouracil, leucovorin, and oxaliplatin (FOLFOX)4 treatment led to inferior PFS (HR = 1.28, 95%CI: 0.79-2.07) and OS (HR = 1.29, 95%CI: 0.79-2.10), which was consistent with the findings in patients with KRAS mutations in exon 2. Then, the update of the PEAK trial and the FIRE-III trial also supported this finding, which would reduce candidates for anti-EGFR therapy but enhance the efficacy. In first-line targeted combination therapy, the regimens of cetuximab plus FOLFOX was called into

  13. Psoriasis in pregnancy: a review (II).

    PubMed

    Ruiz, V; Manubens, E; Puig, L

    2014-11-01

    Scarce scientific evidence is available to define the precise effects that certain drugs might have on embryonic and fetal development if taken by pregnant women with psoriasis, given the ethical concerns that preclude enrolling such women in clinical trials. The little information on the use of biologics during gestation that has been published is based on retrospective and observational studies, and experience with these drugs in this context in psoriasis is still very limited. The literature seems to suggest that biologic therapy is safe during pregnancy, but there is no certainty. This detailed review of accumulated experience with biologic therapy during pregnancy relies mainly on descriptions of the management of other types of rheumatic disease, although the use of these agents in psoriasis is growing steadily. PMID:24314892

  14. Telmisartan aggravates pustular psoriasis

    PubMed Central

    Keerthi, Subramaniam; Rangaraj, Murugaiyan; Karthikeyan, Kaliaperumal

    2015-01-01

    Pustular psoriasis is characterized by abrupt onset of macroscopic pustules associated with erythema and symptoms of burning pain and constitutional symptoms. There are several precipitating factors, both physiological such as pregnancy and routinely prescribed drugs like antihypertensives, antifungals, corticosteroids and progesterone. We present a case of a 50-year-old male patient with pustular psoriasis, well controlled on oral methotrexate, who presented with sudden exacerbation of pustular psoriasis following the use of telmisartan. This case is presented due to the absence of prior reports of telmisartan aggravating pustular psoriasis. PMID:25969662

  15. Anti-platelet therapy and managing ulcer risk.

    PubMed

    Chan, Francis K L

    2012-02-01

    Low-dose aspirin (ASA) has emerged as one of the most important causes of peptic ulcer bleeding in developed countries. Among the risk factors of ASA-associated ulcer bleeding, Helicobacter pylori infection is one of the few that is treatable. Recent evidence showed that among patients with a history of ASA-associated ulcer bleeding, the long-term incidence of recurrent bleeding with ASA use is low after eradication of H. pylori alone. Thus, test-and-treat H. pylori is a potentially useful strategy for ASA users with high ulcer risk. However, the risk of bleeding is further increased by combining other anti-platelet drugs (e.g. clopidogrel) with ASA in acute coronary syndromes and coronary stent placement. There is good evidence that co-therapy with a proton-pump inhibitor (PPI) reduces upper gastrointestinal bleeding with ASA alone or dual anti-platelet therapy. Recently, several meta-analyses of observational studies found that concurrent use of PPI and clopidogrel was associated with increased risk of major adverse cardiovascular events. Overall, the evidence does not suggest a clinically important interaction between PPIs and clopidogrel. However, there is a subset of patients who have reduced conversion of clopidogrel to its active metabolites due to genetic polymorphism of hepatic P-450 (carriers of CYP2C19 loss-of-function alleles). Since PPIs are also metabolized by similar hepatic enzymes, it is uncertain whether patients carrying CY2C19 loss-of-function alleles are susceptible to concomitant PPI use. In the future, management of patients on dual anti-platelet therapy needs to be individualized according to their thrombotic and bleeding risks. PMID:22142030

  16. Ten years of anti-vascular endothelial growth factor therapy.

    PubMed

    Ferrara, Napoleone; Adamis, Anthony P

    2016-06-01

    The targeting of vascular endothelial growth factor A (VEGFA), a crucial regulator of both normal and pathological angiogenesis, has revealed innovative therapeutic approaches in oncology and ophthalmology. The first VEGFA inhibitor, bevacizumab, was approved by the US Food and Drug Administration in 2004 for the first-line treatment of metastatic colorectal cancer, and the first VEGFA inhibitors in ophthalmology, pegaptanib and ranibizumab, were approved in 2004 and 2006, respectively. To mark this tenth anniversary of anti-VEGFA therapy, we discuss the discovery of VEGFA, the successes and challenges in the development of VEGFA inhibitors and the impact of these agents on the treatment of cancers and ophthalmic diseases. PMID:26775688

  17. Anti-IL-4/-13 based therapy in asthma.

    PubMed

    Walsh, Garry M

    2015-09-01

    It is recognised that airway inflammation is key to asthma pathogenesis. Biopharmaceutical approaches have identified new therapies that target key cells and mediators that drive the inflammatory responses in the asthmatic lung. Such an approach resulted in the development of biologics targeted at inhibition of IL-4, IL-5 and IL-13. However, early clinical trials with these biologics in patients with asthma were for the most part disappointing even though they were highly effective in animal models of asthma. It is becoming apparent that significant clinical effects with anti-cytokine-based biologic therapies are more likely in carefully selected patient populations that take asthma phenotypes into account. The development of discriminatory biomarkers and genetic profiling may aid identification of such patients with asthma. This review is an update of the evidence demonstrating the effectiveness or otherwise of the targeting of the TH2 cytokines IL-4 and IL-13 with biologics in patients with asthma. PMID:26021492

  18. Mutually enhancing anti-inflammatory activities of dimethyl fumarate and NF-κB inhibitors--implications for dose-sparing combination therapies.

    PubMed

    Hund, Anna-Carina; Lockmann, Anike; Schön, Michael P

    2016-02-01

    Fumaric acid esters, dimethyl fumarate (DMF) in particular, have been established for the therapy of psoriasis and, more recently, multiple sclerosis. In the light of therapy-limiting dose-dependent side effects, such as gastrointestinal irritation, reducing the effective doses of FAE is a worthwhile goal. In search of strategies to maintain the anti-inflammatory activity of DMF at reduced concentrations, we found that NF-κB inhibition augmented key anti-inflammatory effects of DMF in two complementary experimental settings in vitro. At non-toxic concentrations, both proteasome inhibition with bortezomib as well as blocking NF-κB activation through KINK-1, a small molecule inhibitor of IKKβ-profoundly enhanced DMF-dependent inhibition of nuclear NF-κB translocation in TNFα-stimulated human endothelial cells. This resulted in significant and selective co-operative down-regulation of endothelial adhesion molecules crucial for leucocyte extravasation, namely E-selectin (CD62E), VCAM-1 (CD106) and ICAM-1 (CD54), on both mRNA and protein levels. Functionally, these molecular changes led to synergistically decreased rolling and firm adhesion of human lymphocytes on TNF-activated endothelial cells, as demonstrated in a dynamic flow chamber system. If our in vitro findings can be translated into clinical settings, it is conceivable that anti-inflammatory effects of DMF can be achieved with lower doses than currently used, thus potentially reducing unwanted side effects. PMID:26513635

  19. Evaluating practice patterns for managing moderate to severe plaque psoriasis

    PubMed Central

    Poulin, Yves; Wasel, Norman; Chan, Daphne; Bernstein, Geula; Andrew, Robin; Fraquelli, Elisa; Papp, Kim

    2012-01-01

    Abstract Objective To describe practice patterns for care of Canadian patients with moderate to severe plaque psoriasis. Design Online survey of a consumer panel. Setting Participants were drawn from a population-wide Canadian consumer database. Participants To be eligible to participate, respondents had to have been diagnosed with plaque psoriasis within the past 5 years, and to have had body surface area involvement of 3% or greater in the past 5 years, or to have psoriasis on a sensitive area of the body (hands, feet, scalp, face, or genitals), or to be currently receiving treatment with systemic agents or phototherapy for psoriasis. Main outcome measures Proportion of respondents with psoriasis managed by FPs and other specialists, psoriasis therapies, comorbidities, and patient satisfaction. Results Invitations were sent to 3845 panelists with self-reported psoriasis, of which 514 qualified to complete the survey. Family physicians were reported to be the primary providers for diagnosis and ongoing care of psoriasis in all provinces except Quebec. Overall physician care was reported to be satisfactory by 62% of respondents. Most respondents receiving over-the-counter therapies (55%) or prescribed topical therapies (61%) reported that their psoriasis was managed by FPs. Respondents receiving prescription oral or injectable medications or phototherapy were mainly managed by dermatologists (42%, 74%, and 71% of respondents, respectively). Ongoing management of respondents with body surface area involvement of 10% or greater was mainly split between dermatologists (47%) and FPs (45%), compared with rheumatologists (4%) or other health care professionals (4%). Of those respondents receiving medications for concomitant health conditions, treatment for high blood pressure was most common (92%), followed by treatment for heart disease (75%) and elevated cholesterol and lipid levels (68%). Conclusion Patient-reported practice patterns for the diagnosis and management

  20. Stimulation of anti-tumor immunity by photodynamic therapy

    PubMed Central

    Mroz, Pawel; Hashmi, Javad T; Huang, Ying-Ying; Lange, Norbert; Hamblin, Michael R

    2011-01-01

    Photodynamic therapy (PDT) is a rapidly developing cancer treatment that utilizes the combination of nontoxic dyes and harmless visible light to destroy tumors by generating reactive oxygen species. PDT produces tumor-cell destruction in the context of acute inflammation that acts as a ‘danger signal’ to the innate immune system. Activation of the innate immune system increases the priming of tumor-specific T lymphocytes that have the ability to recognize and destroy distant tumor cells and, in addition, lead to the development of an immune memory that can combat recurrence of the cancer at a later point in time. PDT may be also successfully combined with immunomodulating strategies that are capable of overcoming or bypassing the escape mechanisms employed by the progressing tumor to evade immune attack. This article will cover the role of the immune response in PDT anti-tumor effectiveness. It will highlight the milestones in the development of PDT-mediated anti-tumor immunity and emphasize the combination strategies that may improve this therapy. PMID:21162652

  1. Optimizing the use of topical agents in psoriasis.

    PubMed

    Stein Gold, Linda F

    2014-03-01

    The vast majority of patients with psoriasis have localized disease that is manageable by topical therapy alone, and patients with more severe disease still require topical treatment for plaques that persist despite effective systemic treatment or phototherapy. Nevertheless, little attention today is paid to topical therapy, including new topical treatments.This article briefly addresses key issues that can adversely affect the use of and compliance with currently available topical treatments, as well as new and emerging topical agents for psoriasis. PMID:24979541

  2. Plant extracts for the topical management of psoriasis: a systematic review and meta-analysis.

    PubMed

    Deng, S; May, B H; Zhang, A L; Lu, C; Xue, C C L

    2013-10-01

    Patients with psoriasis frequently use preparations of plant extracts. Physicians need to be aware of the current evidence concerning these products. This review evaluates the efficacy and safety of preparations of plant extracts used topically for psoriasis. Searches were conducted in PubMed, Embase, the Cochrane library, two Chinese databases and article reference lists. Randomized controlled trials investigating extracts of single plants were included. Preparations of multiple plants and combinations of plant extracts plus conventional therapies were excluded. Two authors conducted searches, extracted data and assessed risk of bias. Outcomes used in meta-analyses were: clinical efficacy, Psoriasis Area and Severity Index score, and quality of life and symptom scores. The 12 included studies investigated extracts of: Mahonia aquifolium (n = 5), Aloe vera (n = 3), indigo naturalis (n = 2), kukui nut oil (n = 1) and Camptotheca acuminata nut (n = 1). Methodological quality was variable. Six studies provided data suitable for meta-analysis of clinical efficacy, and five were vs. placebo (relative risk 3·37, 95% confidence interval 1·36-8·33). Experimental studies indicate components of indigo naturalis, Mahonia and Camptotheca have anti-inflammatory, antiproliferative and other actions of relevance to psoriasis. The clinical trial evidence provides limited support for preparations containing extracts of M. aquifolium, indigo naturalis and Aloe vera for the topical management of plaque psoriasis based on multiple studies. No serious adverse events were reported. Because of the small size of most studies and methodological weaknesses, strong conclusions cannot be made. The magnitudes of any effects cannot be measured with accuracy, so it is difficult to assess the clinical relevance of these preparations. PMID:23909714

  3. The cost of psoriasis.

    PubMed

    Crown, William H

    2003-05-01

    Crown discussed findings of a Medstat study probing the economic burden of psoriasis and the presence of comorbidity in psoriasis patients. He also discussed current economic issues in the marketplace, concluding with some thoughts on health economics and biologics--which are shifting the landscape of pharmacotherapy. PMID:18564553

  4. Plasma total antioxidant capacity and peroxidation biomarkers in psoriasis.

    PubMed

    Peluso, Ilaria; Cavaliere, Arturo; Palmery, Maura

    2016-01-01

    Systemic biomarkers of oxidative stress can be relevant for assessment of psoriasis severity, for prediction of the outcome of therapy and of the development of comorbidities. In this review we aimed to evaluate the relationship between plasma total antioxidant capacity (TAC) and peroxidation biomarkers, as well as their association with dyslipidemia and systemic inflammation in psoriasis. The review of 59 case-control comparisons (from 41 studies) and 17 interventions (from 13 studies) suggests that peroxidation markers are more sensitive than TAC in the evaluation of oxidative stress in psoriasis. Although few studies investigated the effect of treatment on oxidative stress, it seems that biological drugs could be the better choice in the treatment of psoriasis. However, considering the limitations of TAC and plasma peroxidation markers, this review suggests that new methods should be developed in order to evaluate systemic oxidative stress in psoriasis. PMID:27377373

  5. [The psychological and social support in patients with psoriasis].

    PubMed

    Makara-Studzińska, Marta; Ziemecki, Piotr; Ziemecka, Anna; Partyka, Iwona

    2013-09-01

    The meaning of non medical forms of support in the treatment of psoriasis is discussed in the paper. Related with psoriasis negative self image and feeling of stigmatization cause various mental disorders. Stress, depression, mental condition affect the appearance of psoriasis. Because of numerous studies and identify the factors and relationships important for psoriasis, patients can take the appropriate psychological and social support. Relaxation techniques, cognitive-behavioral therapy and support groups have a positive effect on the treatment of psoriasis. They reduce the level of stress in the patient, learn emotional control, adequate self-esteem, which leads to the acceptance of the disease and improve the quality of life of the patient. PMID:24224457

  6. Unusual case of B cell lymphoma after immunosuppressive treatment for psoriasis.

    PubMed

    Nosotti, Lorenzo; Baiocchini, Andrea; Bonifati, Claudio; Visco-Comandini, Ubaldo; Mirisola, Concetta; Del Nonno, Franca

    2015-04-18

    Lymphomas may be induced by the systemic immunosuppressive therapies used to treat psoriasis, such as ciclosporin, methotrexate and tumour necrosis factor (TNF)-α blockers. The biologic agents currently used in psoriasis include alefacept, efalizumab, and the TNF-α antagonists etanercept, infliximab, and adalimumab. Infections and cancer are the main possible consequences of intended or unexpected immunosuppression. We report a 59-year-old man with a history of severe psoriasis vulgaris treated with traditional immunosuppressant drugs followed by anti-TNF-α therapy; the patient was firstly hospitalized for an acute cholestatic toxic hepatitis, which we supposed to be related to adalimumab. The first liver biopsy showed active disease with severe hepatocellular damage caused by heavy lymphocytes infiltrate in portal tracts at in the interface with a not conclusive diagnosis of lymphoproliferative disease. The correct diagnosis of T cell/histiocyte- rich large B cell lymphoma (T/HRBCL) was only reached through a gastric biopsy and a second liver biopsy. T/HRBCL is an uncommon morphologic variant of diffuse large B-cell lymphoma not described until now in psoriatic patients receiving immunosuppressive biologic agents. In psoriatic patients, treated with biologic immunosuppressive agents, the suspect of abdominal lymphoma should always be included as differential diagnosis. Abdominal ultrasound evaluation need therefore to be included in the pre-treatment screening as in the follow-up surveillance. PMID:25914782

  7. A Clinician's Guide to the Diagnosis and Treatment of Candidiasis in Patients with Psoriasis.

    PubMed

    Armstrong, April W; Bukhalo, Michael; Blauvelt, Andrew

    2016-08-01

    Many of the molecular pathways associated with psoriasis pathogenesis are also involved in host defense mechanisms that protect against common pathogens. Candida can stimulate the production of cytokines that trigger or exacerbate psoriasis, and many systemic psoriasis treatments may put patients at increased risk for developing oral, cutaneous, and genitourinary candidiasis. Therefore, dermatologists should regularly screen patients with psoriasis for signs of Candida infection, and take steps to effectively treat these infections to prevent worsening of psoriasis symptoms. This review provides an overview of candidiasis epidemiology in patients with psoriasis, followed by a primer on the diagnosis and treatment of superficial Candida infections, with specific guidance for patients with psoriasis. Candidiasis in patients with psoriasis typically responds to topical or oral antifungal therapy. While biologic agents used to treat moderate-to-severe psoriasis, such as tumor necrosis factor-α inhibitors and interleukin-17 inhibitors, are known to increase patients' risk of developing localized candidiasis, the overall risk of infection is low, and candidiasis can be effectively managed in most patients while receiving systemic psoriasis therapies. Thus, the development of candidiasis does not usually necessitate changes to psoriasis treatment regimens. PMID:27435194

  8. Oral Curcumin (Meriva) Is Effective as an Adjuvant Treatment and Is Able to Reduce IL-22 Serum Levels in Patients with Psoriasis Vulgaris

    PubMed Central

    Bonciolini, Veronica; Volpi, Walter; Del Bianco, Elena; Caproni, Marzia

    2015-01-01

    Curcumin is a complementary therapy that may be helpful for the treatment of psoriasis due to its anti-inflammatory, antiangiogenic, antioxidant, and antiproliferative effects. In the present study we performed a randomized, double-blind, placebo-controlled clinical trial to assess the effectiveness of a bioavailable oral curcumin in the treatment of psoriasis. Sixty-three patients with mild-to-moderate psoriasis vulgaris (PASI < 10) were randomly divided into two groups treated with topical steroids and Meriva, a commercially available lecithin based delivery system of curcumin, at 2 g per day (arm 1), or with topical steroids alone (arm 2), both for 12 weeks. At the beginning (T0) and at the end of the therapy (T12), clinical assessment and immunoenzymatic analysis of the serum levels of IL-17 and IL-22 were performed. At T12, both groups achieved a significant reduction of PASI values that, however, was higher in patients treated with both topical steroids and oral curcumin than in patients treated only with topical steroids. Moreover, IL-22 serum levels were significantly reduced in patients treated with oral curcumin. In conclusion, curcumin was demonstrated to be effective as an adjuvant therapy for the treatment of psoriasis vulgaris and to significantly reduce serum levels of IL-22. PMID:26090395

  9. Adherence to Anti Retroviral Therapy (ART) During Muslim Ramadan Fasting

    PubMed Central

    Habib, A. G.; Shepherd, J. C.; Eng, M. K. L.; Babashani, M.; Jumare, J.; Yakubu, U.; Gebi, U. I.; Saad, M.; Ibrahim, H.; Blattner, W. A.

    2010-01-01

    Annual fasting during the month of Ramadan is observed in Muslim countries, some of which have widespread HIV infection. We studied treatment adherence and customary practices among 142 fasting `FT' and 101 non-fasting `NFT' patients on anti-retroviral therapy (ART) in Nigeria. Adherence on ART among FT and NFT patients was similar during Ramadan, 96% and 98%, and ever since commencement of ART, 80% and 88%, respectively. FT patients altered their typical daily behaviors by advancing morning and delaying evening doses thereby prolonging dosing intervals, eating heavier meals pre-dawn and on breakfast at sunset (78%), and changing or reducing their sleeping and waking times (40%). This preliminary study suggests that adherence and drug taking frequency appear uncompromised in FT HIV infected patients on ARVs. PMID:18521736

  10. Psoriasis: new comorbidities*

    PubMed Central

    Machado-Pinto, Jackson; Diniz, Michelle dos Santos; Bavoso, Nádia Couto

    2016-01-01

    Psoriasis is a chronic inflammatory disease associated with several comorbidities. A few decades ago, it was considered an exclusive skin disease but today it is considered a multisystem disease. It is believed that 73% of psoriasis patients have at least one comorbidity. Studies have demonstrated the association of psoriasis with inflammatory bowel disease, uveitis, psychiatric disorders, metabolic syndrome and its components and cardiovascular diseases. The systemic inflammatory state seems to be the common denominator for all these comorbidities. This work aims at presenting a review of the current literature on some new comorbidities that are associated with psoriasis as osteoporosis, obstructive sleep apnea and chronic obstructive pulmonary disease. While there is still controversy, many studies already point to a possible bone involvement in patients with psoriasis, especially in the male group, generally less affected by osteoporosis. Psoriasis and chronic obstructive pulmonary disease present some risk factors in common as obesity, smoking and physical inactivity. Besides, both diseases are associated with the metabolic syndrome. These factors could be potential confounders in the association of the two diseases. Further prospective studies with control of those potential confounders should be developed in an attempt to establish causality. Existing data in the literature suggest that there is an association between obstructive sleep apnea and psoriasis, but studies performed until now have involved few patients and had a short follow-up period. It is, therefore, premature to assert that there is indeed a correlation between these two diseases. PMID:26982772

  11. Psoriasis: new comorbidities.

    PubMed

    Machado-Pinto, Jackson; Diniz, Michelle dos Santos; Bavoso, Nádia Couto

    2016-01-01

    Psoriasis is a chronic inflammatory disease associated with several comorbidities. A few decades ago, it was considered an exclusive skin disease but today it is considered a multisystem disease. It is believed that 73% of psoriasis patients have at least one comorbidity. Studies have demonstrated the association of psoriasis with inflammatory bowel disease, uveitis, psychiatric disorders, metabolic syndrome and its components and cardiovascular diseases. The systemic inflammatory state seems to be the common denominator for all these comorbidities. This work aims at presenting a review of the current literature on some new comorbidities that are associated with psoriasis as osteoporosis, obstructive sleep apnea and chronic obstructive pulmonary disease. While there is still controversy, many studies already point to a possible bone involvement in patients with psoriasis, especially in the male group, generally less affected by osteoporosis. Psoriasis and chronic obstructive pulmonary disease present some risk factors in common as obesity, smoking and physical inactivity. Besides, both diseases are associated with the metabolic syndrome. These factors could be potential confounders in the association of the two diseases. Further prospective studies with control of those potential confounders should be developed in an attempt to establish causality. Existing data in the literature suggest that there is an association between obstructive sleep apnea and psoriasis, but studies performed until now have involved few patients and had a short follow-up period. It is, therefore, premature to assert that there is indeed a correlation between these two diseases. PMID:26982772

  12. [Comorbidity in psoriasis].

    PubMed

    Gerdes, S; Mrowietz, U; Boehncke, W-H

    2016-06-01

    Psoriasis is a systemic chronic inflammatory disease associated with comorbidity. Many epidemiological studies have shown that psoriasis is associated with psoriatic arthritis as well as cardiovascular and metabolic diseases. Furthermore, obesity and psychological diseases such as depression and anxiety disorders are linked with psoriasis and play a central role in its management. The association of psoriasis and its comorbidity can be partly explained by genetic and pathophysiological mechanisms. Approximately 40 psoriasis susceptibility loci have been described with the majority linked to the innate and adaptive immune system. In some associated diseases, such as psoriatic arthritis, an overlap of their genetic susceptibility exists. Pathophysiologically the "psoriatic march" is a model that describes the development of metabolic and cardiovascular diseases due to the presence of underlying systemic inflammation. Dermatologists are the gatekeepers to treatment for patients with psoriasis. The early detection and the management of comorbidity is part of their responsibility. Concepts for the management of psoriasis and tools to screen for psoriatic comorbidity have been developed in order to support dermatologists in daily practice. PMID:27221798

  13. [Chances and risks of anti-VEGF therapy].

    PubMed

    Ziemssen, F; Heiduschka, P; Peters, S; Grisanti, S; Schraermeyer, U

    2008-09-01

    Vascular endothelial growth factor (VEGF) plays a pivotal role in angiogenesis. Through regulation of haemodynamics, haematopoesis and the immune system, endocrinology and reparative processes, inhibition of VEGF can cause multiple adverse events. Previous data suggest that--even after intravitreal injection--systemic exposure might occur, thus bearing the risk of manifestation of side effects. Experience with intravenous administration of the antibody bevacizumab (Avastin) pointed to the potential consequences of a pan-VEGF blockade. The change of haemodynamic parameters implies a potential influence on the patient's morbidity. Studies already conducted during the approval process do not provide sufficient statistical power when evaluating whether systemic events significantly differ between the treatment and control groups. Retinal perfusion showed an altered vascular tone (change in vessel diameter) following anti-VEGF treatment. Physiological fenestration of the choroicapillaris is significantly reduced. Possible effects on the local oxygen supply in ischaemic tissue have to be considered. In contrast to destructive treatment modalities (laser, cryo), VEGF inhibitors promise the prompt and efficient response of retinal neovascularisation and the preservation of a better function (visual fields). The maturation of growing vessels (pericytes) and the secondary formation of membranes are limiting factors with regard to the time-point at which anti-VEGF therapy is most effective. A diligent use of the available drugs has to take into account which types of exudative retinopathy are showing no or only very limited response to the treatment. PMID:18759208

  14. Low-dose, short-term ciclosporin (Neoral®) therapy is effective in improving patients' quality of life as assessed by Skindex-16 and GHQ-28 in mild to severe psoriasis patients.

    PubMed

    Okubo, Yukari; Natsume, Shoko; Usui, Kae; Amaya, Misato; Tsuboi, Ryoji

    2011-05-01

    Therapies for psoriasis have focused not only on ameliorating the severity of the skin lesions, but also on the quality of life (QOL). Here, the efficacy of low-dose, short-term administration of ciclosporin (Neoral®, as CyA) was investigated. Forty-one psoriasis patients were given CyA orally (3 mg/kg per day) twice daily before breakfast and dinner until the psoriatic area and severity index (PASI) scores decreased by at least 75%. Surveys were conducted before and after the therapy to ascertain QOL, itch, nail condition, joint pain, stress associated with topical application and therapy satisfaction. QOL was assessed by using the Japanese version of Skindex-16 specific to skin diseases, and the Japanese version of the GHQ-28, which assesses mental health. Data collected from 35 patients were analyzed. Remission was achieved in 26 patients (74%), and the average length required to achieve remission was 101.5 days. The average PASI score significantly decreased from 17.8 to 3.3 after the therapy. Remission lasted 6 months or longer in 40% of the patients. The average length of time before restarting systemic therapy was 182.0 days. This duration for patients with PASI scores of <13 was 287.5 days while for patients with PASI scores of ≥13, it was significantly shorter at 120.1 days. Five adverse events were recorded in three patients, but were not serious. The total Skindex-16 score significantly decreased especially in the "emotions' and "functioning" categories. GHQ scores also significantly decreased in "somatic symptoms,"anxiety and insomnia," and "depression". With regard to patients' satisfaction with their therapy, 88.5% of the patients reported "satisfied" or "slightly satisfied". These results demonstrate that low-dose, short-term administration of CyA (3 mg/kg per day) is one of the best therapies for psoriasis patients with PASI scores of <13, while QOL assessment is a very useful tool for evaluating the value of therapy. PMID:21352289

  15. Duration of Anti-Tuberculosis Therapy and Timing of Antiretroviral Therapy Initiation: Association with Mortality in HIV-Related Tuberculosis

    PubMed Central

    Cortes, Claudia P.; Wehbe, Firas H.; McGowan, Catherine C.; Shepherd, Bryan E.; Duda, Stephany N.; Jenkins, Cathy A.; Gonzalez, Elsa; Carriquiry, Gabriela; Schechter, Mauro; Padgett, Denis; Cesar, Carina; Madero, Juan Sierra; Pape, Jean W.; Masys, Daniel R.; Sterling, Timothy R.

    2013-01-01

    Background Antiretroviral therapy (ART) decreases mortality risk in HIV-infected tuberculosis patients, but the effect of the duration of anti-tuberculosis therapy and timing of anti-tuberculosis therapy initiation in relation to ART initiation on mortality, is unclear. Methods We conducted a retrospective observational multi-center cohort study among HIV-infected persons concomitantly treated with Rifamycin-based anti-tuberculosis therapy and ART in Latin America. The study population included persons for whom 6 months of anti-tuberculosis therapy is recommended. Results Of 253 patients who met inclusion criteria, median CD4+ lymphocyte count at ART initiation was 64 cells/mm3, 171 (68%) received >180 days of anti-tuberculosis therapy, 168 (66%) initiated anti-tuberculosis therapy before ART, and 43 (17%) died. In a multivariate Cox proportional hazards model that adjusted for CD4+ lymphocytes and HIV-1 RNA, tuberculosis diagnosed after ART initiation was associated with an increased risk of death compared to tuberculosis diagnosis before ART initiation (HR 2.40; 95% CI 1.15, 5.02; P = 0.02). In a separate model among patients surviving >6 months after tuberculosis diagnosis, after adjusting for CD4+ lymphocytes, HIV-1 RNA, and timing of ART initiation relative to tuberculosis diagnosis, receipt of >6 months of anti-tuberculosis therapy was associated with a decreased risk of death (HR 0.23; 95% CI 0.08, 0.66; P=0.007). Conclusions The increased risk of death among persons diagnosed with tuberculosis after ART initiation highlights the importance of screening for tuberculosis before ART initiation. The decreased risk of death among persons receiving > 6 months of anti-tuberculosis therapy suggests that current anti-tuberculosis treatment duration guidelines should be re-evaluated. PMID:24066096

  16. Immune response after photodynamic therapy increases anti-cancer and anti-bacterial effects

    PubMed Central

    Reginato, Eleonora; Wolf, Peter; Hamblin, Michael R

    2014-01-01

    Photodynamic therapy (PDT) is a clinically approved procedure for treatment of cancer and infections. PDT involves systemic or topical administration of a photosensitizer (PS), followed by irradiation of the diseased area with light of a wavelength corresponding to an absorbance band of the PS. In the presence of oxygen, a photochemical reaction is initiated, leading to the generation of reactive oxygen species and cell death. Besides causing direct cytotoxic effects on illuminated tumor cells, PDT is known to cause damage to the tumor vasculature and induce the release of pro-inflammatory molecules. Pre-clinical and clinical studies have demonstrated that PDT is capable of affecting both the innate and adaptive arms of the immune system. Immune stimulatory properties of PDT may increase its beneficial effects giving the therapy wider potential to become more extensively used in clinical practice. Be sides stimulating tumor-specific cytotoxic T-cells capable to destroy distant untreated tumor cells, PDT leads to development of anti-tumor memory immunity that can potentially prevent the recurrence of cancer. The immunological effects of PDT make the therapy more effective also when used for treatment of bacterial infections, due to an augmented infiltration of neutrophils into the infected regions that seems to potentiate the outcome of the treatment. PMID:25364655

  17. 'Upgrading' psoriasis responsibly.

    PubMed

    Boehncke, Sandra; Boehncke, Wolf-Henning

    2014-10-01

    Psoriasis is a 'pacemaker' in dermatology. Substantial progress has been made regarding our understanding of its pathophysiology and genetic background, fuelling developments in cutaneous biology in general. Besides, the clinical perspective on psoriasis is currently changing, taking into consideration comorbidity and the systemic dimensions of this seemingly organ-specific inflammation. The availability of drugs exhibiting fewer contraindications and improved long-term safety opened a discussion around replacing a relatively limited (regarding both objectives and duration) 'therapeutic' by a much broader 'management' approach when it comes to treating psoriasis as a systemic disease. The question arises whether this 'upgrade' is warranted. PMID:25040560

  18. Progress and Prospects of Anti-HBV Gene Therapy Development

    PubMed Central

    Maepa, Mohube B.; Roelofse, Ilke; Ely, Abdullah; Arbuthnot, Patrick

    2015-01-01

    Despite the availability of an effective vaccine against hepatitis B virus (HBV), chronic infection with the virus remains a major global health concern. Current drugs against HBV infection are limited by emergence of resistance and rarely achieve complete viral clearance. This has prompted vigorous research on developing better drugs against chronic HBV infection. Advances in understanding the life cycle of HBV and improvements in gene-disabling technologies have been impressive. This has led to development of better HBV infection models and discovery of new drug candidates. Ideally, a regimen against chronic HBV infection should completely eliminate all viral replicative intermediates, especially covalently closed circular DNA (cccDNA). For the past few decades, nucleic acid-based therapy has emerged as an attractive alternative that may result in complete clearance of HBV in infected patients. Several genetic anti-HBV strategies have been developed. The most studied approaches include the use of antisense oligonucleotides, ribozymes, RNA interference effectors and gene editing tools. This review will summarize recent developments and progress made in the use of gene therapy against HBV. PMID:26263978

  19. Risk of tuberculosis is higher with anti-tumor necrosis factor monoclonal antibody therapy than with soluble tumor necrosis factor receptor therapy: The three-year prospective French Research Axed on Tolerance of Biotherapies registry

    PubMed Central

    Tubach, Florence; Salmon, Dominique; Ravaud, Philippe; Allanore, Yannick; Goupille, Philippe; Bréban, Maxime; Pallot-Prades, Béatrice; Pouplin, Sophie; Sacchi, Antoinette; Chichemanian, Rose Marie; Bretagne, Stéphane; Emilie, Dominique; Lemann, Marc; Lorthololary, Olivier; Mariette, Xavier

    2009-01-01

    Background Tuberculosis (TB) is associated with anti-tumour necrosis factor (TNF) therapy but whether it is drug-specific remains a concern. Our objective was to describe cases of tuberculosis associated with anti-TNF therapy, identify risk factors and estimate the incidence. Methods An incidence study with the French population as reference and a case-control analysis. We collected, for 3 years, cases of TB among French patients receiving anti-TNF therapy, whatever the indication, with two controls treated with anti-TNF agents per case. Results We collected 69 cases of TB in patients treated for rheumatoid arthritis (n=40), spondylarthropathies (n=18), inflammatory colitis (n=9), psoriasis (n=1) and Behçet’s disease (n=1) treated with infliximab (n=36), adalimumab (n=28) and etanercept (n=5). None of the cases had received correct chemoprophylaxis treatment. The sex and age-adjusted incidence rate of TB was 116.7 per 100,000 patient-years. The SIR was 12.2 (95% confidence interval 9.7–15.5) and was higher for therapy with infliximab and adalimumab than for that with etanercept: 18.6 (13.4–25.8) and 29.3 (20.2–42.4) versus 1.8 (0.7–4.3), respectively. In the case-control analysis, the exposure to infliximab or adalimumab versus etanercept was an independent risk factor for TB: odds ratio=13.3 (2.6–69.0) and 17.1 (3.6–80.6), respectively. Other risk factors were age, the first year of anti-TNF treatment, and being born in an endemic area. Conclusions The risk of TB is higher for patients receiving monoclonal-antibody than soluble-receptor anti-TNF therapy. The increased risk with early anti-TNF treatment and the absence of correct chemoprophylaxis treatment favours the reactivation of latent TB. PMID:19565495

  20. A marriage of two “Methusalem” drugs for the treatment of psoriasis?

    PubMed Central

    Glossmann, Hartmut; Reider, Norbert

    2013-01-01

    In this article we present arguments that the “antidiabetic” drug metformin could be useful as an add-on therapy to methotrexate for the treatment of psoriasis and, perhaps, for rheumatoid arthritis as well. Biochemical data suggest that both drugs may share a common cellular target, the AMP-activated protein kinase (AMPK). This enzyme is a master regulator of metabolism and controls a number of downstream targets, e.g., important for cellular growth or function in many tissues including T-lymphocytes. Clinical observations as well as experimental results argue for anti-inflammatory, antineoplastic and antiproliferative activities of metformin and a case-control study suggests that the drug reduces the risk for psoriasis. Patients with psoriasis have higher risk of metabolic syndrome, type 2 diabetes and cardiovascular mortality. Metformin has proven efficacy in the treatment of prediabetes and leads to a pronounced and sustained weight loss in overweight individuals. We expect that addition of metformin to methotrexate can lead to positive effects with respect to the PASI score, reduction of the weekly methotrexate dose and of elevated cardiovascular risk factors in patients with metabolic syndrome and psoriasis. For reasons explained later we suggest that only male, overweight patients are to be included in a pilot trial. On the other side of the coin are concerns that the gastrointestinal side effects of metformin are intolerable for patients under low dose, intermittent methotrexate therapy. Metformin has another side effect, namely interference with vitamin B12 and folate metabolism, leading to elevated homocysteine serum levels. As patients must receive folate supplementation and will be controlled with respect to their B12 status increased hematological toxicity is unlikely to result. PMID:24194965

  1. VEGF involvement in psoriasis.

    PubMed

    Marina, Mihaela Elena; Roman, Iulia Ioana; Constantin, Anne-Marie; Mihu, Carmen Mihaela; Tătaru, Alexandru Dumitru

    2015-01-01

    Vascular endothelial growth factor (VEGF) is a key growth factor, regulating the neovascularization, during embryogenesis, skeletal growth, reproductive functions and pathological processes. The VEGF receptors (VEGFR) are present in endothelial cells and other cell types, such as vascular smooth muscle cells, hematopoietic stem cells, monocytes, neurons, macrophages, and platelets. Angiogenesis is initiated by the activation of vascular endothelial cells through several factors. The excess dermal vascularity and VEGF production are markers of psoriasis. The pathological role of VEGF/VEGFR signaling during the psoriasis onset and evolution makes it a promising target for the treatment of psoriasis. Antibodies and other types of molecules targeting the VEGF pathway are currently evaluated in arresting the evolution of psoriasis. PMID:26609252

  2. Leprosy associated with psoriasis.

    PubMed

    Raiol, Theisla Kely Azevedo; Volpato, Solange Emanuelle; Santana, Jaci Maria; Ferreira, Isabelle Sousa Medeiros Torres; Takano, Daniela Mayumi

    2015-12-01

    Reported cases of leprosy and psoriasis coexistence are uncommon in the literature. Studies suggest a negative association between these two diseases. A case of association between these disorders has been reported. PMID:26964432

  3. Guttate psoriasis outcomes.

    PubMed

    Pfingstler, Lisa F; Maroon, Michele; Mowad, Christen

    2016-02-01

    Guttate psoriasis (GP) typically occurs following an acute infection such as streptococcal pharyngitis. It is thought to have a better prognosis than chronic plaque psoriasis (PP). This retrospective cohort study of 79 patients with GP aims to assess the likelihood of developing PP after the first episode of GP as well as compare clinical and laboratory data in patients with GP who do and do not develop PP. PMID:26919501

  4. Methodology for Anti-Gene Anti-IGF-I Therapy of Malignant Tumours

    PubMed Central

    Trojan, Jerzy; Pan, Yuexin X.; Wei, Ming X.; Ly, Adama; Shevelev, Alexander; Bierwagen, Maciej; Ardourel, Marie-Yvonne; Trojan, Ladislas A.; Alvarez, Alvaro; Andres, Christian; Noguera, Maria C.; Briceno, Ignacio; Aristizabal, Beatriz H.; Kasprzak, Heliodor; Duc, Huynh T.; Anthony, Donald D.

    2012-01-01

    The aim of this study was to establish the criteria for methodology of cellular “anti-IGF-I” therapy of malignant tumours and particularly for glioblastoma multiforme. The treatment of primary glioblastoma patients using surgery, radiotherapy, and chemotherapy was followed by subcutaneous injection of autologous cancer cells transfected by IGF-I antisense/triple helix expression vectors. The prepared cell “vaccines” should it be in the case of glioblastomas or other tumours, have shown a change of phenotype, the absence of IGF-I protein, and expression of MHC-I and B7. The peripheral blood lymphocytes, PBL cells, removed after each of two successive vaccinations, have demonstrated for all the types of tumour tested an increasing level of CD8+ and CD8+28+ molecules and a switch from CD8+11b+ to CD8+11. All cancer patients were supervised for up to 19 months, the period corresponding to minimum survival of glioblastoma patients. The obtained results have permitted to specify the common criteria for “anti-IGF-I” strategy: characteristics sine qua non of injected “vaccines” (cloned cells IGF-I(−) and MHC-I(+)) and of PBL cells (CD8+ increased level). PMID:22400112

  5. The Risk of Chronic Pancreatitis in Patients with Psoriasis: A Population-Based Cohort Study

    PubMed Central

    Chiang, Yi-Ting; Huang, Weng-Foung; Tsai, Tsen-Fang

    2016-01-01

    Background Psoriasis is a chronic systemic inflammatory disorder, and studies have revealed its association with a variety of comorbidities. However, the risk of chronic pancreatitis (CP) in psoriasis has not been studied. This study aimed to investigate the risk of CP among patients with psoriasis. Methods Using the Taiwan National Health Insurance Research Database, this population-based cohort study enrolled 48430 patients with psoriasis and 193720 subjects without psoriasis. Stratified Cox proportional hazards models were used to compare the risks of CP between the patients with and without psoriasis. Results The incidence of CP was 0.61 per 1000 person-years in patients with psoriasis and 0.34 per 1000 person-years in controls during a mean 6.6-year follow-up period. Before adjustment, patients with psoriasis had a significantly higher risk of CP (crude hazard ratio (HR) = 1.81; 95% confidence interval (CI) = 1.53–2.15), and the risk remained significantly higher after adjustments for gender, age group, medications, and comorbidities (adjusted HR (aHR) = 1.76; 95% CI = 1.47–2.10). All psoriasis patient subgroups other than those with arthritis, including those with mild and severe psoriasis and those without arthritis, had significantly increased aHRs for CP, and the risk increased with increasing psoriasis severity. Psoriasis patients taking nonsteroidal anti-inflammatory drugs (aHR = 0.33; 95% CI = 0.22–0.49) and methotrexate (aHR = 0.28; 95% CI = 0.12–0.64) had a lower risk of developing CP after adjustments. Conclusions Psoriasis is associated with a significantly increased risk of CP. The results of our study call for more research to provide additional insight into the relationship between psoriasis and CP. PMID:27467265

  6. Psoriasis and Topical Iranian Traditional Medicine

    PubMed Central

    Atyabi, Akramosadat; Shirbeigi, Laila; Eghbalian, Fateme

    2016-01-01

    Background: Psoriasis is a common chronic inflammatory skin, nails, and joints disease related to the immune system by periods of exacerbations and remissions. It is characterized by thick end, erythematous, and scaling lesions, which affects about 2 to 4 percent of the general population. The disease occurs equally in both sexes and the most common form of the disease is psoriasis vulgaris. The etiology is unknown but genetic and environmental factors, immune system disorders, and gastrointestinal dysfunction appear to be responsible. The aim of this study is to compare psoriasis and Ghooba clinical manifestations and introduce medical treatment of this disease based on authentic books of traditional medicine. Methods: This study is a qualitative literature review based on reliable sources of traditional medicine, such as Canon of Medicine, Makhzan-ul-Adwiah, Qrabadyne kabir, Zakhireh-ye Khwarazm shahi, Tib-e-Akbari and Exir-e-Azam. Results: Probably, in traditional medicine, the most similar disease to psoriasis is Ghooba. That is scaly lesion concomitant with itching and articular pain in most cases. The causes of disease are poor performance of the liver and spleen and stomach, as well as excessive consumption of foods such as beef and veal, eggplant and fish. Several local treatments such as wheat germ oil, flaxseed oil, black seed oil, and violet oil were recommended. Conclusion: Psoriasis is a chronic, debilitating physical, mental, and sexual disease for which genetic, environmental and immunological factors are recommended for its etiology. This problem could be treated by the oral and topical medications symptomatically; however, major side effects are associated with recent treatments. Change in lifestyle, prevention issues, as well as herbal therapy are recommended for the treatment of psoriasis in traditional medicine. PMID:27516685

  7. What is the risk of intracranial bleeding during anti-VEGF therapy?

    PubMed

    Carden, Craig P; Larkin, James M G; Rosenthal, Mark A

    2008-08-01

    Vascular endothelial growth factor (VEGF) is a key mediator of physiological and pathological angiogenesis. All solid tumors are dependent on pathological angiogenesis, and anti-VEGF therapy has demonstrated clinical benefit in breast, colorectal, non-small-cell lung, and renal carcinomas. Central nervous system metastases are common in many of these tumor types. An increased risk of bleeding has been reported with anti-VEGF therapy, but the risk of intracranial bleeding is unknown with this type of therapy. We reviewed the available data to investigate the risk of intracranial bleeding with anti-VEGF therapy in the presence and absence of CNS metastases. The PubMed and Medline databases and the Proceedings of the American Society of Clinical Oncology (ASCO) annual meetings were searched for articles, abstracts, and presentations of clinical trials. We identified 57 trials examining the safety and efficacy of anti-VEGF therapy in a total of 10,598 patients. Four trials examined the use of anti-VEGF therapy in treating patients with brain metastases. The presence of CNS metastases was a stated exclusion criterion in 76% of trials. The rate of intracranial bleeding was negligible. We conclude that there is no trial evidence that anti-VEGF therapy confers an increased risk of intracranial bleeding, even in the presence of CNS metastases. Future trials of anti-VEGF therapy should not exclude patients with controlled CNS metastases at enrollment. PMID:18539884

  8. Plasma exchange and leukapheresis in psoriasis--no effect?

    PubMed

    Liedén, G; Skogh, M

    1986-01-01

    Nine patients with severe or therapy-resistant psoriasis were treated by plasma exchanges or leukapheresis; one received both treatments in succession. None of the patients showed convincing signs of improvement. We therefore conclude that there is little evidence for the existence of a "psoriasis factor", the removal of which, it has been suggested, would explain the beneficial effects of dialysis. Nor is there anything to indicate that the removal of large numbers of leukocytes would bring about healing. PMID:3789803

  9. Anti-diabetic therapies affect risk of pancreatic cancer

    PubMed Central

    Li, Donghui; Yeung, Sai-Ching J.; Hassan, Manal M.; Konopleva, Marina; Abbruzzese, James L.

    2009-01-01

    Background & Aims Anti-diabetic drugs have been found to have various effects on cancer in experimental systems and in epidemiological studies, although the association between these therapeutics and the risk of human pancreatic cancer has not been explored. We investigated the effect of anti-diabetic therapies on the risk of pancreatic cancer. Methods A hospital-based, case-control study was conducted at M.D. Anderson Cancer Center from 2004 through 2008 involving 973 patients with pancreatic adenocarcinoma (including 259 diabetics) and 863 controls (including 109 diabetics). Information on diabetes history and other risk factors was collected by personal interview. The frequencies of use of insulin, insulin secretagogues, thiazolidinediones, metformin and other antidiabetic medications among diabetics were compared between cases and controls. The risk of pancreatic cancer was estimated using unconditional logistic regression analysis. Results Diabetics that had taken metformin had a significantly lower risk of pancreatic cancer, compared with those that had not taken metformin (OR=0.38; 95% CI, 0.22–0.69; P=0.001) with adjustments for demographic, clinical and risk factors. This difference remained statistically significant when the analysis was restricted to patients with a duration of diabetes >2 years or those never used insulin. In contrast, diabetics that had taken insulin or insulin secretagogues had a significantly higher risk of pancreatic cancer, compared with diabetics that had not take these drugs. Use of thiazolidinediones did not significantly modify pancreatic cancer risk. Conclusions Metformin use was associated with reduced risk, and insulin or insulin secretagogues use were associated with increased risk of pancreatic cancer in diabetics. PMID:19375425

  10. [Integrated approach to comorbidity in patients with psoriasis.Working Group on Psoriasis-associated Comorbidities].

    PubMed

    Daudén, E; Castañeda, S; Suárez, C; García-Campayo, J; Blasco, A J; Aguilar, M D; Ferrándiz, C; Puig, L; Sánchez-Carazo, J L

    2012-01-01

    The relationship between psoriasis and associated diseases has drawn particular interest in recent years. To provide appropriate management of psoriasis from an early stage, it is necessary to include prompt diagnosis of concomitant disease and to prevent and treat any comorbidity found. Such an integrated approach also serves to ensure that the drugs used to treat associated diseases do not interfere with the management of psoriasis, and vice versa. This clinical practice guideline on the management of comorbidity in psoriasis has been drawn up to help dermatologists to achieve an integrated approach to this inflammatory disease. The guide focuses primarily on the diseases most often found in patients with psoriasis, which include psoriatic arthritis, cardiovascular disease, nonalcoholic fatty liver disease, inflammatory bowel disease, lymphoma, skin cancer, anxiety, and depression. Cardiovascular disease is approached through the study of its major risk factors (obesity, diabetes mellitus, hypertension, dyslipidemia, and metabolic syndrome). Other cardiovascular risk factors related to lifestyle, such as smoking and alcohol consumption, are also discussed. The overall aim of this guide is to provide the dermatologist with a precise, easy to-use tool for systematizing the diagnosis of comorbidity in these patients and to facilitate decisions regarding referral and treatment once associated diseases have been found. The specific objectives are as follows: a) to review the most common diseases associated with psoriasis, including the prevalence of each one and its importance to the dermatologist; b) to provide guidelines for the physical examination, diagnostic tests, and clinical criteria on which to base a preliminary diagnosis; c) to establish criteria for the appropriate referral of patients with suspected comorbidity; d) to provide information on how therapies for psoriasis may modify the course of associated diseases, and e) to provide information concerning

  11. Health Conditions Associated with Psoriasis

    MedlinePlus

    ... Psoriatic Arthritis Info Kit Resources Community icon: Link text: Post your questions in our online community and ... psoriasis and psoriatic arthritis. Talk Psoriasis icon: Link text: Contact our Patient Navigators for free and confidential ...

  12. Death receptors as targets for anti-cancer therapy

    PubMed Central

    Papenfuss, Kerstin; Cordier, Stefanie M; Walczak, Henning

    2008-01-01

    Human tumour cells are characterized by their ability to avoid the normal regulatory mechanisms of cell growth, division and death. The classical chemotherapy aims to kill tumour cells by causing DNA damage-induced apoptosis. However, as many tumour cells posses mutations in intracellular apoptosis-sensing molecules like p53, they are not capable of inducing apoptosis on their own and are therefore resistant to chemotherapy. With the discovery of the death receptors the opportunity arose to directly trigger apoptosis from the outside of tumour cells, thereby circumventing chemotherapeutic resistance. Death receptors belong to the tumour necrosis factor receptor superfamily, with tumour necrosis factor (TNF) receptor-1, CD95 and TNF-related apoptosis-inducing ligand-R1 and -R2 being the most prominent members. This review covers the current knowledge about these four death receptors, summarizes pre-clinical approaches engaging these death receptors in anti-cancer therapy and also gives an overview about their application in clinical trials conducted to date. PMID:19210756

  13. Anti-TNF therapy: past, present and future

    PubMed Central

    Monaco, Claudia; Nanchahal, Jagdeep; Taylor, Peter

    2015-01-01

    While for a century therapeutics has been dominated by small molecules, i.e. organic chemicals of ~400Da absorbable via the gut, this is no longer the case. There are now a plethora of important medicines which are proteins and injectable, which have dramatically improved the therapy of many inflammatory diseases and of cancer. Most of these are monoclonal antibodies, some are receptor Ig Fc fusion proteins, others are cytokines or enzymes. The key to this new aspect of therapeutics has been the filling of unmet needs, and the consequent commercial success, which promoted further research and development. The first ‘biologic’ for a common disease, rheumatoid arthritis (RA), was a monoclonal antibody, infliximab, to human tumour necrosis factor (TNF). This was based on our work, which is described in this review, summarizing how TNF was defined as a good target in RA, how it was developed is described here, as well as future indications for anti-TNF and related agents. Biologics are now the fastest growing sector of therapeutics. PMID:25411043

  14. Psoriasis: classical and emerging comorbidities*

    PubMed Central

    de Oliveira, Maria de Fátima Santos Paim; Rocha, Bruno de Oliveira; Duarte, Gleison Vieira

    2015-01-01

    Psoriasis is a chronic inflammatory systemic disease. Evidence shows an association of psoriasis with arthritis, depression, inflammatory bowel disease and cardiovascular diseases. Recently, several other comorbid conditions have been proposed as related to the chronic inflammatory status of psoriasis. The understanding of these conditions and their treatments will certainly lead to better management of the disease. The present article aims to synthesize the knowledge in the literature about the classical and emerging comorbidities related to psoriasis. PMID:25672294

  15. Relation between the Peripherofacial Psoriasis and Scalp Psoriasis

    PubMed Central

    Kim, Kyung Ho; Ahn, Ji Young; Park, Mi Youn

    2016-01-01

    Background Facial involvement of psoriasis is known to be one of the clinical manifestations that indicate the severity of the psoriasis and thought to be more closely associated with certain distribution. Centrofacial (CF) psoriasis has been suggested to be related with severity of systemic disease while peripherofacial (PF) psoriasis has been thought to have connection with scalp psoriasis. Objective To analyze the epidemiologic characteristics, clinical features and subjective feelings of patients with facial psoriasis and to find out relationship between scalp psoriasis and facial involvement according to the facial types. Methods One hundred nineteen facial psoriasis patients were categorized into 3 types according to the distribution: PF type, CF type and mixed facial (MF) type. Onset and duration of facial and scalp psoriasis, and their relationship were questioned. Severity and extent of psoriasis on whole body, face, and scalp were rated by clinicians. Results There was no significant difference of whole body psoriasis area and severity index (PASI) and body surface area (BSA) score but scalp PASI and BSA was much higher in PF psoriasis compared to CF psoriasis (scalp PASI, 17.9 vs. 10.1; p=0.005) (scalp BSA, 40.9 vs. 22.2; p=0.002). According to the questionnaire, patient's objective feeling about the spreading of scalp lesion to facial area was markedly more prominent in the patients with peripheral involvement (PF+MF, 90.1%; CF, 54.2%; p<0.0001). Conclusion Among subtypes of facial psoriasis, PF psoriasis is closely associated with spreading of scalp lesion into the face rather than reflecting the disease severity. PMID:27489422

  16. Patient-relevant treatment goals in psoriasis.

    PubMed

    Blome, Christine; Gosau, Ramona; Radtke, Marc A; Reich, Kristian; Rustenbach, Stephan J; Spehr, Christina; Thaçi, Diamant; Augustin, Matthias

    2016-03-01

    Patient-oriented care requires therapeutic decisions to agree with the patients' treatment needs and goals. This study addressed the following questions: What is important to psoriasis patients starting systemic treatment? How stable are these preferences within the first year of treatment? Are treatment goals associated with age, gender, or treatment success? The importance of treatment goals was assessed for patients with moderate-to-severe psoriasis in the German Psoriasis Registry (PsoBest) at baseline (onset of a systemic treatment; n = 3066) and at a 1-year follow-up (n = 1444) using the Patient Benefit Index (PBI). Treatment success was measured with PBI global score and Psoriasis Area Severity Index (PASI). Patients with moderate-to-severe psoriasis pursued a wide range of different goals. The most general treatment goals were rated most relevant, including skin healing and quick skin improvement (94.8/94.5 % "quite" or "very" important), confidence in the therapy (93.0 %), control over the disease (92.3 %), and a clear diagnosis and therapy (89.6 %). Further important goals related to not being in fear of the disease getting worse (84.8 %), reduction in itching (83.9 %), burning (70.6 %), and pain (60.6 %) as well as attaining a normal everyday life (78.4 %) and low treatment burden (64.2-77.9 %). Goals were mostly not associated with sex and gender. Goal importance slightly increased with treatment success. In a substantial proportion of patients (30.3-54.7 %) goal importance changed within 1 year after onset of systemic treatment. We conclude that treatment goal importance should be assessed in clinical practice on a regular basis. PMID:26688112

  17. Purine and pyrimidine excretion in psoriasis

    PubMed Central

    Simmonds, H. A.; Bowyer, A.

    1974-01-01

    1 Urinary purine excretion has been investigated in two healthy controls and two patients with psoriasis, one a hyperuricaemic, one a normouricaemic. No difference was detected between the patients and controls. Therapy with allopurinol effectively lowered blood and urinary uric acid levels and produced a deficit in total urinary oxypurine excretion in both controls and patients with psoriasis. The concomitant increase in xanthine excretion was greater than the increase in hypoxanthine excretion and xanthine/hypoxanthine ratios (average 0.70 and 1.0 prior to therapy) were increased by allopurinol to an average of 3.0 and 3.8 respectively in the two groups. Allopurinol also reduced the excretion of 8-hydroxy-7-methyl guanine but no effect on the excretion levels of other minor purine bases was noted. 2 Allopurinol was metabolized similarly by both patients and controls, 84% of the administered allopurinol being accounted for as urinary metabolites. 74% of the drug in the urine was excreted as oxipurinol, 26% as unchanged allopurinol plus allopurinol riboside, the remainder being oxipurinol riboside. 3 Pseudouridine excretion in 25 healthy controls was 86.5 ± 17.8 mg/24 hours. Pseudouridine excretion was not excessive in the patients with psoriasis and was not altered by allopurinol therapy. 4 No abnormality or difference in purine or pyrimidine excretion in either patient was detected prior to or during therapy which could be related to the epidermal lesion. PMID:22454896

  18. The Inflammatory Response in Psoriasis: a Comprehensive Review.

    PubMed

    Deng, Yaxiong; Chang, Christopher; Lu, Qianjin

    2016-06-01

    Psoriasis is a chronic inflammatory autoimmune disease characterized by an excessively aberrant hyperproliferation of keratinocytes. The pathogenesis of psoriasis is complex and the exact mechanism remains elusive. However, psoriasis is thought to result from a combination of genetic, epigenetic, and environmental influences. Recent studies have identified that epigenetic factors including dysregulated DNA methylation levels, abnormal histone modification and microRNAs expressions are involved in the development of psoriasis. The interplay of immune cells and cytokines is another critical factor in the pathogenesis of psoriasis. These factors or pathways include Th1/Th2 homeostasis, the Th17/Treg balance and the IL-23/Th17 axis. Th17 is believed particularly important in psoriasis due to its pro-inflammatory effects and its involvement in an integrated inflammatory loop with dendritic cells and keratinocytes, contributing to an overproduction of antimicrobial peptides, inflammatory cytokines, and chemokines that leads to amplification of the immune response. In addition, other pathways and signaling molecules have been found to be involved, including Th9, Th22, regulatory T cells, γδ T cells, CD8(+) T cells, and their related cytokines. Understanding the pathogenesis of psoriasis will allow us to develop increasingly efficient targeted treatment by blocking relevant inflammatory signaling pathways and molecules. There is no cure for psoriasis at the present time, and much of the treatment involves managing the symptoms. The biologics, while lacking the adverse effects associated with some of the traditional medications such as corticosteroids and methotrexate, have their own set of side effects, which may include reactivation of latent infections. Significant challenges remain in developing safe and efficacious novel targeted therapies that depend on a better understanding of the immunological dysfunction in psoriasis. PMID:27025861

  19. Anti-TNFalpha therapy of rheumatoid arthritis: what can we learn about chronic disease?

    PubMed

    Feldmann, Marc; Brennan, Fionula M; Paleolog, Ewa; Cope, Andrew; Taylor, Peter; Williams, Richard; Woody, Jim; Maini, Ravinder N

    2004-01-01

    The importance of tumour necrosis factor (TNF)alpha in rheumatoid arthritis (RA) was initially proposed on the basis of analysis of cytokine gene regulation at the local site of the disease, the synovium. This was then verified in animal models and established in an extensive series of clinical trials, culminating in now 250000 treated patients with either of two approved TNF inhibitors, antibody or fusion protein. The degree and magnitude of clinical benefit has enabled analyses of the mechanism by which anti-TNF benefits, and hence insights into important steps in the disease process. It was found that essentially all aspects of RA were ameliorated, and important mechanisms of benefit involved diminution of multiple pro-inflammatory cytokines, adhesion molecules and chemokines, leading to reduced cell trafficking, reduced angiogenesis and most importantly halting of joint destruction. What of the problems? Safety is better than prior drugs, but there is a small increase in severe infections, smaller than might have been anticipated. Cost is the major drawback limiting greater use. In view of the central pathological processes down-regulated, and their role in many diseases, the early clinical success of anti-TNF in RA led to subsequent successful trials and registration in Crohn's disease and juvenile rheumatoid arthritis, and successful trials in ankylosing spondylitis, psoriasis and psoriatic arthritis. The era of anti-cytokine therapeutics is just dawning. PMID:15027483

  20. Psoriasis and comorbidities. Epidemiological studies.

    PubMed

    Egeberg, Alexander

    2016-02-01

    Psoriasis is a prevalent chronic inflammatory disease whose exact aetiology is not fully understood, but both genetic and environmental factors have been implicated in the onset and progression of the disease. At the skin level, psoriasis is characterized by localized or widespread thick raised silvery-white scaling and pruritic plaques and studies have shown that psoriasis negatively affects patients' quality of life, and depression occurs more often in patients with psoriasis. However, data have shown that psoriasis is a systemic disease which affects the joints, vasculature, and other tissues as well. Indeed, approximately one-third of patients with psoriasis develop psoriatic arthritis, and patients with severe psoriasis have a shortened life expectancy. Although our knowledge of the pathogenesis of psoriasis has advanced significantly in the past decade, as have the pharmacological treatment options which are now available, several important knowledge gaps remain. Many of the proinflammatory mediators involved in psoriasis have also been implicated in some central nervous system (CNS) diseases. However, studies on associations between psoriasis and CNS diseases are scarce. Based on nationwide registry data from the entire Danish population, the present thesis examined the associations between psoriasis and certain CNS diseases. The specific objectives of this work were to investigate the independent impact of depression on the risk of cardiovascular disease (CVD) in patients with psoriasis, the relationship between psoriasis and uveitis, and the risk of incident multiple sclerosis (MS) following the onset of psoriasis, respectively. The main results were a significantly increased risk of myocardial infarction, stroke, and CVD death in patients with psoriasis during stages of acute depression. Moreover, we found a bidirectional relationship between psoriasis and uveitis, where the occurrence of either disease significantly increased the risk of the other

  1. [Highly Active AntiRetroviral Therapy and opportunistic protozoan infections].

    PubMed

    Pozio, E

    2004-06-01

    Opportunistic parasite infections (OPIs) are an important cause of morbidity and mortality in persons infected with HIV. In industrialised countries, the use of Highly Active AntiRetroviral Therapy (HAART) results to be effective in suppressing the HIV viral load, with a quantitative and qualitative improvement in the CD4+ T-cell count followed by a strong reduction of opportunistic infections including those caused by parasites. These successes have been mainly attributed to the reconstitution of the cell immunity, which play the most important role in controlling OPIs. However, there are many clinical reports and several laboratory results, which suggest that the control of OPIs in HIV-positive persons under HAART is also induced by the anti-HIV protease inhibitors (PIs), which inhibit the aspartyl proteases of the parasites. The non-conventional use of HIV-PIs seems to be an alternative way for the treatment of parasitic infections, which should be deeply investigated. Of five longitudinal studies carried out before and after the introduction of HAART, four studies showed a strong reduction of toxoplasmic encephalitis (TE) in HIV-positive persons under HAART, whereas in another study, no difference was observed in the incidence rate of TE before and after the introduction of HAART. The influence of HAART in reducing TE has been also confirmed in a randomised, controlled clinical trial, which showed that there is no increase in the risk of developing TE after beginning HAART, even though HIV-infected persons with TE had a discontinuing prophylaxis for Toxoplasma gondii. Four HIV protease inhibitors were tested against the T. gondii virulent RH strain in vitro, alone or in association with pyrimethamine or sulfadiazine. Ritonavir and nelfinavir were highly inhibitory for the parasite growth. Furthermore, none of the antiviral drugs negatively affected the anti-Toxoplasma activity of pyrimethamine or sulfadiazine. In HIV-Leishmania co-infections, a changing pattern

  2. A new era in the management of psoriasis? The biologics: facts and controversies.

    PubMed

    Ferrándiz, Carlos; Carrascosa, Jose Manuel; Boada, Aram

    2010-01-01

    During the last 30 years, the tremendous progress in our knowledge of the pathogenesis of psoriasis has led to the development of new agents, the so-called biologics, that have revolutionized the management of severe psoriasis. Dermatologists and patients see this emerging therapy as a new perspective in the state of the art in managing moderate to severe psoriasis. After a few years of use in daily practice, we may begin to analyze the power of the currently available biologic agents in the management of severe psoriasis from the perspective of facts. PMID:20082956

  3. Darwinian medicine and psoriasis.

    PubMed

    Romaní de Gabriel, J

    2015-04-01

    Darwinian medicine, or evolutionary medicine, regards some pathological conditions as attempts by the organism to solve a problem or develop defense mechanisms. At certain stages of human evolution, some diseases may have conferred a selective advantage. Psoriasis is a high-penetrance multigenic disorder with prevalence among whites of up to 3%. Psoriatic lesions have been linked with enhanced wound-healing qualities and greater capacity to fight infection. Leprosy, tuberculosis, and infections caused by viruses similar to human immunodeficiency virus have been postulated as environmental stressors that may have selected for psoriasis-promoting genes in some human populations. The tendency of patients with severe psoriasis to develop metabolic syndrome may reflect the body's attempt to react to environmental stresses and warning signs by triggering insulin resistance and fat storage. PMID:25129580

  4. Role of the hypoxic tumor microenvironment in the resistance to anti-angiogenic therapies

    PubMed Central

    Rapisarda, Annamaria; Melillo, Giovanni

    2009-01-01

    Angiogenesis, a key process for the growth of human cancers, has recently been exploited for the development of a novel class of cancer therapeutics that was thought to have wide applications and not to induce resistance in the clinical setting. Indeed, anti-angiogenic therapy has become an important option for the management of several human malignancies. However, a significant number of patients either do not respond to anti-angiogenic agents or fairly rapidly develop resistance. In addition, the benefit of anti-angiogenic therapy is relatively short-lived and the majority of patients eventually relapses and progresses. Several mechanisms of resistance to anti-angiogenic therapy have been recently proposed. The current review focuses on the role of intratumor hypoxia as a mechanism of resistance to anti-angiogenic agents and speculates on therapeutic approaches that might circumvent resistance and thereby improve clinical outcome. PMID:19394890

  5. Superimposed linear psoriasis: differential therapeutic response of linear and nonlinear lesions.

    PubMed

    Seitz, C S; Garbaraviciene, J; Bröcker, E-B; Hamm, H

    2009-07-01

    Linear psoriasis is a very unusual clinical variation of psoriasis. Typical clinical features include early onset of erythematosquamous lesions along Blaschko's lines, ability to elicit psoriatic features, absence of pruritus and positive family history for psoriasis. Recently, the term 'superimposed linear psoriasis' was coined for cases with development of nonlinear psoriatic lesions at predilection sites in later life. We report a 19-year-old woman meeting all criteria for the diagnosis of superimposed linear psoriasis including typical histological features. Remarkably, treatment with topical steroids and dithranol cleared the psoriatic lesions on predilection sites whereas the linear lesions were resistant to topical therapy. Linear psoriatic lesions are believed to be caused by genetic alterations in early embryogenesis leading to loss of heterozygosity at a gene locus involved in the pathogenesis of psoriasis. Comparison of mosaic keratinocytes derived from linear lesions with wild-type keratinocytes from the same person may therefore allow identification of key regulatory genes. PMID:19094135

  6. Photo-distributed lichenoid eruption secondary to direct anti-viral therapy for hepatitis C.

    PubMed

    Simpson, Cory L; McCausland, Drew; Chu, Emily Y

    2015-10-01

    Novel direct anti-viral agents are emerging as effective treatments for hepatitis C virus (HCV) and provide an alternative to the year-long standard therapy with interferon and ribavirin. However, cutaneous side effects from these new medications, including rash, pruritus and photosensitivity, are among the most commonly reported adverse events and have resulted in therapy discontinuation in some cases. Here, we report two cases of a photo-distributed lichenoid eruption that occurred within 1  month of starting anti-viral therapy with simeprevir and sofosbuvir without interferon or ribavirin. This report provides the first histologic description of the cutaneous eruption associated with direct anti-viral therapy for HCV and highlights the importance of recognizing and treating the often intolerable dermatologic side effects of these novel medications, the incidence of which is likely to increase as direct anti-viral agents may become the standard of care for HCV. PMID:25974215

  7. A guide to prepare patients with inflammatory bowel diseases for anti-TNF-α therapy.

    PubMed

    Chebli, Júlio Maria Fonseca; Gaburri, Pedro Duarte; Chebli, Liliana Andrade; da Rocha Ribeiro, Tarsila Campanha; Pinto, André Luiz Tavares; Ambrogini Júnior, Orlando; Damião, Adérson Omar Mourão Cintra

    2014-01-01

    Current therapy of moderate-to-severe inflammatory bowel disease (IBD) often involves the use of anti-tumor necrosis factor alpha (TNF-α) agents. Although very effective, theses biologics place the patient at increased risk for developing infections and lymphomas, the latter especially when in combination with thiopurines. Appropriate patient selection, counseling, and education are all important features for the successful use of anti-TNF-α therapy. A thorough history to rule-out contraindications of this therapy and emphasis on monitoring guidelines are important steps preceding administration of anti-TNF-α agents. This therapy should only be considered if a recent evaluation has established that the patient has active IBD. In addition, it is important to exclude disease mimickers. Anti-TNF-α agents have been considered to present a globally favorable benefit/risk ratio. However, it is important that in routine practice, initiation of anti-TNF-α therapy be carefully discussed with the patient, extensively explaining the potential benefits and risks of such treatment. Prior to starting anti-TNF-α therapy, the patients need to be screened for latent tuberculosis, hepatitis B virus infection, and (usually) hepatitis C virus and HIV infection. Vaccination schedules of IBD patients should be evaluated and updated prior to the commencement of anti-TNF-α therapy. Ordinarily, immunization in adult patients with IBD should not deviate from recommended guidelines for the general population. With the exception of live vaccines, immunizations can be safely administered in patients with IBD, even those on immunosuppressants or biologics. The purpose of this review is providing an overview of appropriate steps to prepare patients with IBD for anti-TNF-α therapy. PMID:24667275

  8. Clinical efficacy and drug resistance of anti-epidermal growth factor receptor therapy in colorectal cancer

    PubMed Central

    Kocoglu, Hakan; Velibeyoglu, Fatih Mehmet; Karaca, Mustafa; Tural, Deniz

    2016-01-01

    Colorectal cancer (CRC) ranked third in cancer related death and its incidence has been increasing worldwide. In recent decades important therapeutic advances have been developed in treatment of metastatic CRC (mCRC), such as monoclonal antibodies against epidermal growth factor receptor (anti-EGFR), which provided additional clinical benefits in mCRC. However, anti-EGFR therapies have limited usage due to approximately 95% of patients with KRAS mutated mCRC do not response to anti-EGFR treatment. Thus, KRAS mutation is predictive of nonresponse to anti-EGFR therapies but it alone is not a sufficient basis to decide who should not be received such therapies because; approximately fifty percent (40%-60%) of CRC patients with wild-type KRAS mutation also have poor response to anti-EGFR based treatment. This fact leads us to suspect that there must be other molecular determinants of response to anti-EGFR therapies which have not been identified yet. Current article summarizes the clinical efficacy of anti-EGFR therapies and also evaluates its resistance mechanisms. PMID:26798432

  9. Targeting miR-21 to treat psoriasis.

    PubMed

    Guinea-Viniegra, Juan; Jiménez, María; Schonthaler, Helia B; Navarro, Raquel; Delgado, Yolanda; Concha-Garzón, María José; Tschachler, Erwin; Obad, Susanna; Daudén, Esteban; Wagner, Erwin F

    2014-02-26

    Psoriasis is a common inflammatory skin disease with limited treatment options that is characterized by a complex interplay between keratinocytes, immune cells, and inflammatory mediators. MicroRNAs (miRNAs) are regulators of gene expression and play critical roles in many human diseases. A number of miRNAs have been described to be up-regulated in psoriasis, but their causal contribution to disease development has not been demonstrated. We confirm that miR-21 expression is increased in epidermal lesions of patients with psoriasis and that this leads to reduced epidermal TIMP-3 (tissue inhibitor of matrix metalloproteinase 3) expression and activation of TACE (tumor necrosis factor-α-converting enzyme)/ADAM17 (a disintegrin and metalloproteinase 17). Using patient-derived skin samples and mouse models of psoriasis, we demonstrate that increased miR-21 may be a consequence of impaired transcriptional activity of Jun/activating protein 1 (AP-1), leading to activation of the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (Stat3) pathway. Inhibition of miR-21 by locked nucleic acid (LNA)-modified anti-miR-21 compounds ameliorated disease pathology in patient-derived psoriatic skin xenotransplants in mice and in a psoriasis-like mouse model. Targeting miR-21 may represent a potential therapeutic option for the treatment of psoriasis. PMID:24574341

  10. Combination of nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy as a novel therapeutic application to manage the pain and treat many clinical conditions

    NASA Astrophysics Data System (ADS)

    Halasa, Salaheldin; Dickinson, Eva

    2014-02-01

    From hypertension to diabetes, cancer to HIV, stroke to memory loss and learning disorders to septic shock, male impotence to tuberculosis, there is probably no pathological condition where nitric oxide does not play an important role. Nitric oxide is an analgesic, immune-modulator, vasodilator, anti-apoptotic, growth modulator, angiogenetic, anti-thrombotic, anti-inflammatory and neuro-modulator. Because of the above actions of nitric oxide, many clinical conditions associated with abnormal Nitric oxide (NO) production and bioavailability. Our novel therapeutic approach is to restore the homeostasis of nitric oxide and replace the lost cells by combining nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy.

  11. Mechanisms of Action of Topical Corticosteroids in Psoriasis

    PubMed Central

    Uva, Luís; Miguel, Diana; Pinheiro, Catarina; Antunes, Joana; Cruz, Diogo; Ferreira, João; Filipe, Paulo

    2012-01-01

    Psoriasis is a lifelong, chronic, and immune-mediated systemic disease, which affects approximately 1–3% of the Caucasian population. The different presentations of psoriasis require different approaches to treatment and appropriate prescriptions according to disease severity. The use of topical therapy remains a key component of the management of almost all psoriasis patients, and while mild disease is commonly treated only with topical agents, the use of topical therapy as adjuvant therapy in moderate-to-severe disease may also be helpful. This paper focuses on the cutaneous mechanisms of action of corticosteroids and on the currently available topical treatments, taking into account adverse effects, bioavailability, new combination treatments, and strategies to improve the safety of corticosteroids. It is established that the treatment choice should be tailored to match the individual patient's needs and his/her expectations, prescribing to each patient the most suitable vehicle. PMID:23213332

  12. Anti-tumor immune response after photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Mroz, Pawel; Castano, Ana P.; Wu, Mei X.; Kung, Andrew L.; Hamblin, Michael R.

    2009-06-01

    Anti-tumor immunity is stimulated after PDT due a number of factors including: the acute inflammatory response caused by PDT, release of antigens from PDT-damaged tumor cells, priming of the adaptive immune system to recognize tumor-associated antigens (TAA), and induction of heat-shock proteins. The induction of specific CD8+ T-lymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy as it would allow the treatment of tumors that may have already metastasized. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime naÃve T-cells that recognize TAA epitopes. We have carried out in vivo PDT with a BPD-mediated vascular regimen using a pair of BALB/c mouse colon carcinomas: CT26 wild type expressing the naturally occurring retroviral antigen gp70 and CT26.CL25 additionally expressing beta-galactosidase (b-gal) as a model tumor rejection antigen. PDT of CT26.CL25 cured 100% of tumors but none of the CT26WT tumors (all recurred). Cured CT26.CL25 mice were resistant to rechallenge. Moreover mice with two bilateral CT26.CL25 tumors that had only one treated with PDT demonstrated spontaneous regression of 70% of untreated contralateral tumors. T-lymphocytes were isolated from lymph nodes of PDT cured mice that recognized a particular peptide specific to b-gal antigen. T-lymphocytes from LN were able to kill CT26.CL25 target cells in vitro but not CT26WT cells as shown by a chromium release assay. CT26.CL25 tumors treated with PDT and removed five days later had higher levels of Th1 cytokines than CT26 WT tumors showing a higher level of immune response. When mice bearing CT26WT tumors were treated with a regimen of low dose cyclophosphamide (CY) 2 days before, PDT led to 100% of cures (versus 0% without CY) and resistance to rechallenge. Low dose CY is thought to deplete regulatory T-cells (Treg, CD4+CD25+foxp

  13. Immunology of Psoriasis

    PubMed Central

    Lowes, Michelle A.; Suárez-Fariñas, Mayte; Krueger, James G.

    2014-01-01

    The skin is the front line of defense against insult and injury and contains many epidermal and immune elements that comprise the skin-associated lymphoid tissue (SALT). The reaction of these components to injury allows an effective cutaneous response to restore homeostasis. Psoriasis vulgaris is the best-understood and most accessible human disease that is mediated by T cells and dendritic cells. Inflammatory myeloid dendritic cells release IL-23 and IL-12 to activate IL-17-producing T cells, Th1 cells, and Th22 cells to produce abundant psoriatic cytokines IL-17, IFN-γ, TNF, and IL-22. These cytokines mediate effects on keratinocytes to amplify psoriatic inflammation. Therapeutic studies with anticytokine antibodies have shown the importance of the key cytokines IL-23, TNF, and IL-17 in this process. We discuss the genetic background of psoriasis and its relationship to immune function, specifically genetic mutations, key PSORS loci, single nucleotide polymorphisms, and the skin transcriptome. The association between comorbidities and psoriasis is reviewed by correlating the skin transcriptome and serum proteins. Psoriasis-related cytokine-response pathways are considered in the context of the transcriptome of different mouse models. This approach offers a model for other inflammatory skin and autoimmune diseases. PMID:24655295

  14. Psoriasis and ultraviolet radiation

    SciTech Connect

    Farber, E.M.; Nall, L. )

    1993-09-01

    Prevention and detection screening programs as a public health service in curtailing the ever-increasing incidence of all forms of skin cancer are reviewed. The effect of solar and artificial ultraviolet radiation on the general population and persons with psoriasis is examined. 54 refs.

  15. Itchy, Scaly Skin? Living with Psoriasis

    MedlinePlus

    ... exit disclaimer . Subscribe Itchy, Scaly Skin? Living With Psoriasis The thick, red, scaly skin of psoriasis can ... Diet Itchy, Scaly Skin? Wise Choices Links Treating Psoriasis Doctors often use a trial-and-error approach ...

  16. Metabolic and hypoxic adaptation to anti-angiogenic therapy: a target for induced essentiality

    PubMed Central

    McIntyre, Alan; Harris, Adrian L

    2015-01-01

    Anti-angiogenic therapy has increased the progression-free survival of many cancer patients but has had little effect on overall survival, even in colon cancer (average 6–8 weeks) due to resistance. The current licensed targeted therapies all inhibit VEGF signalling (Table1). Many mechanisms of resistance to anti-VEGF therapy have been identified that enable cancers to bypass the angiogenic blockade. In addition, over the last decade, there has been increasing evidence for the role that the hypoxic and metabolic responses play in tumour adaptation to anti-angiogenic therapy. The hypoxic tumour response, through the transcription factor hypoxia-inducible factors (HIFs), induces major gene expression, metabolic and phenotypic changes, including increased invasion and metastasis. Pre-clinical studies combining anti-angiogenics with inhibitors of tumour hypoxic and metabolic adaptation have shown great promise, and combination clinical trials have been instigated. Understanding individual patient response and the response timing, given the opposing effects of vascular normalisation versus reduced perfusion seen with anti-angiogenics, provides a further hurdle in the paradigm of personalised therapeutic intervention. Additional approaches for targeting the hypoxic tumour microenvironment are being investigated in pre-clinical and clinical studies that have potential for producing synthetic lethality in combination with anti-angiogenic therapy as a future therapeutic strategy. PMID:25700172

  17. Targeting Metabolic Symbiosis to Overcome Resistance to Anti-angiogenic Therapy.

    PubMed

    Pisarsky, Laura; Bill, Ruben; Fagiani, Ernesta; Dimeloe, Sarah; Goosen, Ryan William; Hagmann, Jörg; Hess, Christoph; Christofori, Gerhard

    2016-05-10

    Despite the approval of several anti-angiogenic therapies, clinical results remain unsatisfactory, and transient benefits are followed by rapid tumor recurrence. Here, we demonstrate potent anti-angiogenic efficacy of the multi-kinase inhibitors nintedanib and sunitinib in a mouse model of breast cancer. However, after an initial regression, tumors resume growth in the absence of active tumor angiogenesis. Gene expression profiling of tumor cells reveals metabolic reprogramming toward anaerobic glycolysis. Indeed, combinatorial treatment with a glycolysis inhibitor (3PO) efficiently inhibits tumor growth. Moreover, tumors establish metabolic symbiosis, illustrated by the differential expression of MCT1 and MCT4, monocarboxylate transporters active in lactate exchange in glycolytic tumors. Accordingly, genetic ablation of MCT4 expression overcomes adaptive resistance against anti-angiogenic therapy. Hence, targeting metabolic symbiosis may be an attractive avenue to avoid resistance development to anti-angiogenic therapy in patients. PMID:27134168

  18. Clinical improvement in psoriasis with specific targeting of interleukin-23.

    PubMed

    Kopp, Tamara; Riedl, Elisabeth; Bangert, Christine; Bowman, Edward P; Greisenegger, Elli; Horowitz, Ann; Kittler, Harald; Blumenschein, Wendy M; McClanahan, Terrill K; Marbury, Thomas; Zachariae, Claus; Xu, Danlin; Hou, Xiaoli Shirley; Mehta, Anish; Zandvliet, Anthe S; Montgomery, Diana; van Aarle, Frank; Khalilieh, Sauzanne

    2015-05-14

    Psoriasis is a chronic inflammatory skin disorder that affects approximately 2-3% of the population worldwide and has severe effects on patients' physical and psychological well-being. The discovery that psoriasis is an immune-mediated disease has led to more targeted, effective therapies; recent advances have focused on the interleukin (IL)-12/23p40 subunit shared by IL-12 and IL-23. Evidence suggests that specific inhibition of IL-23 would result in improvement in psoriasis. Here we evaluate tildrakizumab, a monoclonal antibody that targets the IL-23p19 subunit, in a three-part, randomized, placebo-controlled, sequential, rising multiple-dose phase I study in patients with moderate-to-severe psoriasis to provide clinical proof that specific targeting of IL-23p19 results in symptomatic improvement of disease severity in human subjects. A 75% reduction in the psoriasis area and severity index (PASI) score (PASI75) was achieved by all subjects in parts 1 and 3 (pooled) in the 3 and 10 mg kg(-1) groups by day 196. In part 2, 10 out of 15 subjects in the 3 mg kg(-1) group and 13 out of 14 subjects in the 10 mg kg(-1) group achieved a PASI75 by day 112. Tildrakizumab demonstrated important clinical improvement in moderate-to-severe psoriasis patients as demonstrated by improvements in PASI scores and histological samples. PMID:25754330

  19. Tumor necrosis factor-alpha inhibitor-induced psoriasis or psoriasiform exanthemata: first 120 cases from the literature including a series of six new patients.

    PubMed

    Wollina, Uwe; Hansel, Gesina; Koch, André; Schönlebe, Jaqueline; Köstler, Erich; Haroske, Gunter

    2008-01-01

    TNFalpha inhibitor was carried out in 47 patients either alone or in association with adjuvant anti-psoriatic therapy (mostly topical). This resulted in complete remission in 21 patients, partial remission in 20 patients, and stable disease in another three patients; in the other three patients, the outcome was not reported. TNFalpha inhibition was continued in 47 patients but anti-psoriatic adjuvant therapy was introduced. The outcome in this group was complete remission in 22 patients, partial remission in 25 patients, and stable disease in 2 patients. The response rate (complete remission plus partial remission) was 93.2% and 95.9%, respectively, in each group. In six patients, switching from one TNFalpha inhibitor to another one immediately after cutaneous adverse effects occurred resulted in an improvement in five patients. In nine patients, a second TNFalpha inhibitor was initiated after a break in TNFalpha inhibition. The response to a second or third drug in these patients was mixed. The underlying pathomechanisms of induction of psoriasis or psoriasiform exanthemata by TNFalpha inhibitors remain elusive but there is reason to assume that induction of such adverse events has more than one pathophysiology. PMID:18092839

  20. Design, Synthesis and in Vitro Degradation of a Novel Co-Drug for the Treatment of Psoriasis

    PubMed Central

    Lau, Wing Man; Heard, Charles M.; White, Alex W.

    2013-01-01

    Psoriasis is a common, chronic and relapsing inflammatory skin disease. It affects approximately 2% of the western population and has no cure. Combination therapy for psoriasis often proves more efficacious and better tolerated than monotherapy with a single drug. Combination therapy could be administered in the form of a co-drug, where two or more therapeutic compounds active against the same condition are linked by a cleavable covalent bond. Similar to the pro-drug approach, the liberation of parent moieties post-administration, by enzymatic and/or chemical mechanisms, is a pre-requisite for effective treatment. In this study, a series of co-drugs incorporating dithranol in combination with one of several non-steroidal anti-inflammatory drugs, both useful for the treatment of psoriasis, were designed, synthesized and evaluated. An ester co-drug comprising dithranol and naproxen in a 1:1 stoichiometric ratio was determined to possess the optimal physicochemical properties for topical delivery. The co-drug was fully hydrolyzed in vitro by porcine liver esterase within four hours. When incubated with homogenized porcine skin, 9.5% of the parent compounds were liberated after 24 h, suggesting in situ esterase-mediated cleavage of the co-drug would occur within the skin. The kinetics of the reaction revealed first order kinetics, Vmax = 10.3 µM·min−1 and Km = 65.1 µM. The co-drug contains a modified dithranol chromophore that was just 37% of the absorbance of dithranol at 375 nm and suggests reduced skin/clothes staining. Overall, these findings suggest that the dithranol-naproxen co-drug offers an attractive, novel approach for the treatment of psoriasis. PMID:24300448

  1. Combination of everolimus and tacrolimus: a potentially effective regimen for recalcitrant psoriasis.

    PubMed

    Wei, Kai-Che; Lai, Ping-Chin

    2015-01-01

    Severe forms of psoriasis that are refractory to conventional therapies are often difficult to manage. The mammalian target of rapamycin (mTOR) inhibitors potentially have versatile effects toward putative psoriatic pathologic pathways. Therefore, mTOR inhibitors may offer a range of new therapeutic options for patients with psoriasis. We describe a 55-year-old male renal transplant patient with refractory psoriasis. We adjusted his antirejection regimen and put him on everolimus (Certican(®); Novartis, Basel, Switzerland; a semisynthetic macrolide, belonging to the mTOR inhibitors family) with low-dose tacrolimus. This combination regimen maintained his graft function and successfully controlled his psoriasis. His skin lesions never recurred in the next 18 months. To our knowledge, this is the first report showing that the combination of everolimus and tacrolimus could be used to treat recalcitrant psoriasis. The relative benefit-risk profiles of such therapies worth further investigation. PMID:25285355

  2. Psoriasis pathophysiology: current concepts of pathogenesis

    PubMed Central

    Krueger, J; Bowcock, A

    2005-01-01

    Psoriasis vulgaris is a common skin disorder characterised by focal formation of inflamed, raised plaques that constantly shed scales derived from excessive growth of skin epithelial cells. The disease is defined by a series of linked cellular changes in the skin: hyperplasia of epidermal keratinocytes, vascular hyperplasia and ectasia, and infiltration of T lymphocytes, neutrophils, and other types of leucocyte in affected skin. In a relatively short period, psoriasis vulgaris has been conceptualised as a T lymphocyte mediated autoimmune disease and new biological therapies that target T cells have just entered routine clinical practice. Similarly, rapid progress has been made towards dissecting cellular and molecular pathways of inflammation that contribute to disease pathogenesis. This short review presents current pathogenic concepts that have emerged from genetic, genomic, and cellular information obtained in basic studies and from clinical studies of selective immune targeting drugs. PMID:15708932

  3. Small Molecules in the Treatment of Psoriasis.

    PubMed

    Torres, Tiago; Filipe, Paulo

    2015-08-01

    Preclinical Research Psoriasis is an inflammatory systemic skin disease that affects various parts of the body requiring long-term management due to its chronic nature. Available treatment options include topical, systemic or biological therapies, which have long-term limitations associated to toxicity, tolerability and risk for adverse effects requiring its intermittent use and close monitoring. Small molecules modulate proinflammatory cytokines, selectively inhibit signaling pathways and showing potential to treat inflammatory diseases in patients not responding to conventional treatments. Presently, small molecules available are phosphodiesterase 4 inhibitors or Janus kinase inhibitors. Other small molecules under development for psoriasis include fumaric acid esters, amygdalin analogs, protein kinase C inhibitors, mitogen-activated protein kinase inhibitors, spleen protein kinase inhibitors, other tyrosine kinase inhibitors, sphingosine 1-phosphate receptor agonists, and A3 adenosine receptor agonists. These new treatment options represent important advances in the development of specific drugs to respond to the goals of treatment and improve patient quality of life. PMID:26255795

  4. Increased Risk of Diabetes and Likelihood of Receiving Diabetes Treatment in Patients with Psoriasis

    PubMed Central

    Azfar, Rahat S.; Seminara, Nicole M.; Shin, Daniel B.; Troxel, Andrea B.; Margolis, David J.; Gelfand, Joel M.

    2013-01-01

    Objective Psoriasis is a common chronic inflammatory disorder that has been mechanistically linked to type II diabetes mellitus. We sought to assess the risk of incident diabetes in patients with psoriasis and to evaluate diabetes treatment patterns among patients with psoriasis and incident diabetes. Design Population-based cohort study. Setting UK-based electronic medical records. Patients We matched 108,132 psoriasis patients aged 18–90 years to 430,716 unexposed patients based on practice and time of visit. For our nested study, only patients who developed incident diabetes during our study time were included. Main Outcome Measure(s) Incident diabetes and adjusted risk of pharmacotherapy among those with incident diabetes. Results The fully adjusted HRs (95% CI) for incident diabetes were 1.14 (1.10–1.18), 1.11 (1.07, 1.15), and 1.46 (1.30, 1.65) in the overall, mild and severe psoriasis groups, respectively. Among those with incident diabetes and severe psoriasis, the adjusted risk for receiving diabetes pharmacotherapy was 1.55 (1.15–2.10). Conclusions Our results suggest that psoriasis is an independent risk factor for the development of type II diabetes mellitus in a dose dependent manner, and that patients with severe psoriasis who develop diabetes are more likely to receive systemic diabetic therapies in comparison to diabetics without psoriasis. PMID:22710320

  5. Multifunctional liposomes for enhanced anti-cancer therapy

    NASA Astrophysics Data System (ADS)

    Falcao, Claudio Borges

    2011-12-01

    with half of the concentration needed for G3139 alone in CL to reduce the cell viability by 40%. Also, it was found greater apoptotic signal in cells treated with CLs containing D-(KLAKLAK)2/G3139 complexes than CLs with G3139 only. In vivo, D-(KLAKLAK) 2/G3139 complexes in CL significantly inhibited tumor growth compared to the saline treated group, through apoptosis induction. However, the mechanism involved in cell death by apoptosis seems to be independent of reduction of bcl-2 protein levels. PEG2000 at 1% mol could significantly reduce activity of PCL formulation towards B16(F10) cells compared to CLs. After pre-incubation at pH 7.4, PCL and pH-PCL had decreased activity compared to CL towards B16(F10) cells. After pre-incubation at pH 5.0, while CL and PCL had the same activity with the cells as in neutral pH, pH-PCL formulation had its PEG cleaved and its cytotoxicity was restored against the melanoma cells. Thus, D-(KLAKLAK)2/G3139 complexes in CL had enhanced anti-cancer therapy, through apoptosis, than G3139 alone in CL in vitro and in vivo. In vitro, PCL and pH-PCL particles obtained can have a prolonged blood residence time, and, once a tumor tissue is reached, pH-PCL can have its cytotoxicity restored because of hydrolysis of cleavable PEG at a lowered pH.

  6. Paeoniflorin suppresses inflammatory response in imiquimod-induced psoriasis-like mice and peripheral blood mononuclear cells (PBMCs) from psoriasis patients.

    PubMed

    Chen, Tao; Fu, Li-Xin; Zhang, Li-Wen; Yin, Bin; Zhou, Pei-Mei; Cao, Na; Lu, Yong-Hong

    2016-08-01

    Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders, characterized by hyperproliferation of keratinocytes, dilation and growth of dermal capillary vasculature, and cellular infiltration of T cells, dendritic cells (DCs), and neutrophils. Paeoniflorin (PF), the principal component of total glucosides of paeony (TGP), displays anti-inflammatory and antioxidant properties in several animal models. In this study, we investigated the anti-inflammatory effects and mechanisms of PF in imiquimod (IMQ)-induced psoriasis-like mouse model. The effects of PF on inflammatory cytokine expression in peripheral blood mononuclear cells (PBMCs) from patients with psoriasis vulgaris were also observed. Our results indicated that PF effectively attenuated the clinical and histopathologic changes in IMQ-induced psoriasis-like mouse model. Furthermore, PF reduced the infiltration of T cells, CD11c(+)DCs, and neutrophils in lesional skin. In addition, PF also significantly decreased the mRNA expression of inflammatory cytokines, such as IL-17, INF-γ, IL-6, and TNF-α, in IMQ-induced psoriasis-like mouse model and PBMCs from patients with psoriasis vulgaris. Hence, our data suggest that PF can inhibit leukocyte infiltration and decrease the expression of inflammatory cytokines such as IL-17, INF-γ, IL-6, and TNF-α. PF might be a candidate drug for the treatment of psoriasis. PMID:27348512

  7. Psoriasis and Associated Psychiatric Disorders

    PubMed Central

    Abreu, José Luís Pio Da Costa; Reis, José Pedro Gaspar Dos; Figueiredo, Américo Manuel Da Costa

    2016-01-01

    Introduction and objective: Psoriasis is a chronic skin disease with a high impact on self-esteem and patients’ health-related quality of life. In the last decades some studies have pointed out mental disorders associated with psoriasis and the etiopathogenic mechanisms behind that co-existence. This work compiles psychopathology associated with psoriasis and further analyzes the etiopathogenesis of psoriasis and mental disorders. Methods: A systematic review of the literature was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and using the “5S” levels of organization of evidence from healthcare research, as previously described. Results: Psoriasis is linked with many mental disorders, both in the psychotic and neurotic sprectrum. Chronic stress diminishes hypothalamic-pituitary-adrenal axis and upregulates sympathetic-adrenal-medullary responses, stimulating pro-inflammatory cytokines. Then, it maintains and exacerbates psoriasis and some of its mental disorders. High levels of pro-inflammatory cytokines connect psoriasis, psychiatric conditions, and other comorbidities of psoriasis (such as atherosclerosis) within a vicious cycle. Furthermore, the etiopathogenesis of the link between each psychiatric comorbidity and psoriasis has its own subtleties, including the cooccurrence of other comorbidities, the parts of the body affected by psoriasis, treatments, and biological and psychosocial factors. Conclusion: The study of psychopathology can amplify our understanding about the etiopathogenesis of psoriasis and associated mental disorders. Patients would benefit from a psychodermatologic approach. The adequate treatment should take into account the mental disorders associated with psoriasis as well as the circumstances under which they occur. PMID:27386050

  8. Successful treatment of pediatric psoriasis with Indigo naturalis composite ointment.

    PubMed

    Lin, Yin-Ku; Yen, Hung-Rong; Wong, Wen-Rou; Yang, Sien-Hung; Pang, Jong-Hwei Su

    2006-01-01

    The treatment of psoriasis in children is still an intractable problem and demands a long-term therapy with prolonged efficacy that is free from serious adverse events. Many modes of therapy are currently in use but the disease is often resistant to treatment owing to the unacceptable toxicity that leads to poor compliance. Therefore, to develop an alternative treatment is indispensable. Traditional Chinese medicine has been documented for over 1000 years to provide various effective treatments for inflammatory skin diseases. Herein, we report an 8-year-old boy with recalcitrant pediatric psoriasis who, after multiple treatment failures with conventional antipsoriatic medications, showed remarkable clinical improvement with 8 weeks of topical treatment with Indigo naturalis composite ointment. Remission has lasted for over 2 years until now. Our patient's response suggests that topical Indigo naturalis composite ointment may provide a safe and effective alternative treatment for pediatric psoriasis. PMID:17014654

  9. Clinical use of anti-TNF therapy and increased risk of infections

    PubMed Central

    Ali, Tauseef; Kaitha, Sindhu; Mahmood, Sultan; Ftesi, Abdul; Stone, Jordan; Bronze, Michael S

    2013-01-01

    Biologics such as antitumor necrosis factor (anti-TNF) drugs have emerged as important agents in the treatment of many chronic inflammatory diseases, especially in cases refractory to conventional treatment modalities. However, opportunistic infections have become a major safety concern in patients on anti-TNF therapy, and physicians who utilize these agents must understand the increased risks of infection. A literature review of the published data on the risk of bacterial, viral, fungal, and parasitic infections associated with anti-TNF therapy was performed and the clinical presentation, diagnostic tests, management, and prevention of opportunistic infections in patients receiving anti-TNF therapy were reviewed. Awareness of the therapeutic potential and associated adverse events is necessary for maximizing therapeutic benefits while minimizing adverse effects from anti-TNF treatments. Patients should be adequately vaccinated when possible and closely monitored for early signs of infection. When serious infections occur, withdrawal of anti-TNF therapy may be necessary until the infection has been identified and properly treated. PMID:23569399

  10. Recent insights in nanotechnology-based drugs and formulations designed for effective anti-cancer therapy.

    PubMed

    Piktel, Ewelina; Niemirowicz, Katarzyna; Wątek, Marzena; Wollny, Tomasz; Deptuła, Piotr; Bucki, Robert

    2016-01-01

    The rapid development of nanotechnology provides alternative approaches to overcome several limitations of conventional anti-cancer therapy. Drug targeting using functionalized nanoparticles to advance their transport to the dedicated site, became a new standard in novel anti-cancer methods. In effect, the employment of nanoparticles during design of antineoplastic drugs helps to improve pharmacokinetic properties, with subsequent development of high specific, non-toxic and biocompatible anti-cancer agents. However, the physicochemical and biological diversity of nanomaterials and a broad spectrum of unique features influencing their biological action requires continuous research to assess their activity. Among numerous nanosystems designed to eradicate cancer cells, only a limited number of them entered the clinical trials. It is anticipated that progress in development of nanotechnology-based anti-cancer materials will provide modern, individualized anti-cancer therapies assuring decrease in morbidity and mortality from cancer diseases. In this review we discussed the implication of nanomaterials in design of new drugs for effective antineoplastic therapy and describe a variety of mechanisms and challenges for selective tumor targeting. We emphasized the recent advantages in the field of nanotechnology-based strategies to fight cancer and discussed their part in effective anti-cancer therapy and successful drug delivery. PMID:27229857

  11. Psoriasis in the U.S. Medicare population: prevalence, treatment, and factors associated with biologic use

    PubMed Central

    Takeshita, Junko; Gelfand, Joel M.; Li, Penxiang; Pinto, Lionel; Yu, Xinyan; Rao, Preethi; Viswanathan, Hema N.; Doshi, Jalpa A.

    2015-01-01

    Psoriasis is a common chronic inflammatory disorder, primarily of the skin. Despite an aging population, knowledge of the epidemiology of psoriasis and its treatments among the elderly is limited. We examined the prevalence of psoriasis and its treatments, with a focus on biologics and identification of factors associated with biologic use, using a nationally representative sample of Medicare beneficiaries in 2011. Based on several psoriasis identification algorithms, the claims-based prevalence for psoriasis in the United States ranged from 0.51% to 1.23%. Treatments employed for moderate to severe psoriasis (phototherapy, oral systemic, or biologic therapies) were received by 27.3% of the total psoriasis sample, of whom 37.2% used biologics. Patients without Medicare Part D low-income subsidies had 70% lower odds of having received biologics than those with low-income subsidies (odds ratio 0.30; 95% confidence interval, 0.19– 0.46). Similarly, the odds of having received biologics was 69% lower among black patients than white patients (0.31; 0.16–0.60). This analysis identified potential financial and racial barriers to receipt of biologic therapies and underscores the need for additional studies to further define the epidemiology and treatment of psoriasis among the elderly. PMID:26214380

  12. Psoriasis in the US Medicare Population: Prevalence, Treatment, and Factors Associated with Biologic Use.

    PubMed

    Takeshita, Junko; Gelfand, Joel M; Li, Penxiang; Pinto, Lionel; Yu, Xinyan; Rao, Preethi; Viswanathan, Hema N; Doshi, Jalpa A

    2015-12-01

    Psoriasis is a common chronic inflammatory disorder, primarily of the skin. Despite an aging population, knowledge of the epidemiology of psoriasis and its treatments among the elderly is limited. We examined the prevalence of psoriasis and its treatments, with a focus on biologics and identification of factors associated with biologic use, using a nationally representative sample of Medicare beneficiaries in 2011. On the basis of several psoriasis identification algorithms, the claims-based prevalence for psoriasis in the United States ranged from 0.51 to 1.23%. Treatments used for moderate-to-severe psoriasis (phototherapy, oral systemic, or biologic therapies) were received by 27.3% of the total psoriasis sample, of whom 37.2% used biologics. Patients without a Medicare Part D low-income subsidy (LIS) had 70% lower odds of having received biologics than those with LIS (odds ratio 0.30; 95% confidence interval, 0.19-0.46). Similarly, the odds of having received biologics were 69% lower among black patients compared with white patients (0.31; 0.16-0.60). This analysis identified potential financial and racial barriers to receipt of biologic therapies and underscores the need for additional studies to further define the epidemiology and treatment of psoriasis among the elderly. PMID:26214380

  13. Benefits and risks of combining anti-tumor necrosis factor with immunomodulator therapy in pediatric inflammatory bowel disease.

    PubMed

    Cozijnsen, Martinus A; Escher, Johanna C; Griffiths, Anne; Turner, Dan; de Ridder, Lissy

    2015-04-01

    Since the introduction of anti-tumor necrosis factor (TNF) therapy as treatment of inflammatory bowel disease (IBD), care of pediatric and adult patients with IBD has significantly improved. To further improve treatment efficacy and durability, multiple trials have compared the efficacy of combination therapy, using anti-TNF therapy combined with an immunomodulator (a thiopurine or methotrexate), with that of anti-TNF monotherapy with contradicting results. The safety of combined therapy has been questioned after several reported cases of hepatosplenic T-cell lymphoma in young patients with IBD so treated. Physicians prescribing anti-TNF therapy to patients with IBD are required to weigh the benefits of combined therapy with its risks. To inform physicians treating children with IBD of these benefits and risks, we reviewed studies in pediatric and adult patients with IBD comparing efficacy, durability, and/or safety of combined therapy with anti-TNF monotherapy. PMID:25723615

  14. Help Desk Answers: What's the most effective topical Tx for scalp psoriasis?

    PubMed

    Thomas, Stephanie K; Hamilton, Tanya

    2016-06-01

    Single-agent therapy with a very potent or potent topical corticosteroid appears more effective than other topical agents, including vitamin D₃ analogues, for treating scalp psoriasis. PMID:27474825

  15. Alopecia secondary to anti-tumor necrosis factor-alpha therapy.

    PubMed

    Ribeiro, Lara Beatriz Prata; Rego, Juliana Carlos Gonçalves; Estrada, Bruna Duque; Bastos, Paula Raso; Piñeiro Maceira, Juan Manuel; Sodré, Celso Tavares

    2015-01-01

    Biologic drugs represent a substantial progress in the treatment of chronic inflammatory immunologic diseases. However, its crescent use has revealed seldom reported or unknown adverse reactions, mainly associated with anti-tumor necrosis factor (anti-TNF). Psoriasiform cutaneous reactions and few cases of alopecia can occur in some patients while taking these drugs. Two cases of alopecia were reported after anti-TNF therapy. Both also developed psoriasiform lesions on the body. This is the second report about a new entity described as 'anti-TNF therapy-related alopecia', which combines clinical and histopathological features of both alopecia areata and psoriatic alopecia. The recognition of these effects by specialists is essential for the proper management and guidance of these patients. PMID:25830994

  16. Discontinuation of anti-VEGF cancer therapy promotes metastasis through a liver revascularization mechanism.

    PubMed

    Yang, Yunlong; Zhang, Yin; Iwamoto, Hideki; Hosaka, Kayoko; Seki, Takahiro; Andersson, Patrik; Lim, Sharon; Fischer, Carina; Nakamura, Masaki; Abe, Mitsuhiko; Cao, Renhai; Skov, Peter Vilhelm; Chen, Fang; Chen, Xiaoyun; Lu, Yongtian; Nie, Guohui; Cao, Yihai

    2016-01-01

    The impact of discontinuation of anti-VEGF cancer therapy in promoting cancer metastasis is unknown. Here we show discontinuation of anti-VEGF treatment creates a time-window of profound structural changes of liver sinusoidal vasculatures, exhibiting hyper-permeability and enlarged open-pore sizes of the fenestrated endothelium and loss of VE-cadherin. The drug cessation caused highly leaky hepatic vasculatures permit tumour cell intravasation and extravasation. Discontinuation of an anti-VEGF antibody-based drug and sunitinib markedly promotes liver metastasis. Mechanistically, host hepatocyte, but not tumour cell-derived vascular endothelial growth factor (VEGF), is responsible for cancer metastasis. Deletion of hepatocyte VEGF markedly ablates the 'off-drug'-induced metastasis. These findings provide mechanistic insights on anti-VEGF cessation-induced metastasis and raise a new challenge for uninterrupted and sustained antiangiogenic therapy for treatment of human cancers. PMID:27580750

  17. The effect of phototherapy on systemic inflammatory process in patients with plaque psoriasis.

    PubMed

    Batycka-Baran, Aleksandra; Besgen, Petra; Wolf, Ronald; Szepietowski, Jacek C; Prinz, Joerg C

    2016-08-01

    Psoriasis is a common, chronic immune-mediated inflammatory disease. The inflammatory process in psoriasis has systemic effects and may influence the development of psoriatic comorbidities. The systemic action of phototherapy in patients with psoriasis has been so far poorly elucidated. We aimed to investigate the expression of genes encoding selected psoriasis-related cytokines in peripheral blood mononuclear cells (PBMCs) isolated from patients with psoriasis before and after treatment with phototherapy. 17 patients with mild to moderate plaque psoriasis were treated with narrow band-UVB (NB-UVB), 8 patients with moderate to severe plaque psoriasis with bath-psoralen-ultraviolet A therapy (PUVA). PBMCs were isolated by Ficoll gradient density centrifugation. Expression of genes encoding TNF-α, IL-17A, IL-6, IL-1 β, INF-γ, and IL-10 in PBMCs of patients with psoriasis before and after phototherapy was analyzed with quantitative RT-PCR. Treatment with NB-UVB therapy led to a significant decrease in IL-17A, TNF-α, and IL-6 mRNA levels in PBMCs (p=0.003; p=0.042; p=0.019, respectively). Following treatment with bath-PUVA therapy, we observed a significant decrease in TNF-α and IL-6 mRNA levels in PBMCs (p=0.031, p=0.035, respectively). Treatment with phototherapy in patients with psoriasis may affect systemic inflammation by downregulation of the expression of genes encoding proinflammatory cytokines in PBMCs, implicated in the development of psoriasis and psoriatic comorbidities. PMID:27314537

  18. Anti-CD3/Anti-CXCL10 Antibody Combination Therapy Induces a Persistent Remission of Type 1 Diabetes in Two Mouse Models.

    PubMed

    Lasch, Stanley; Müller, Peter; Bayer, Monika; Pfeilschifter, Josef M; Luster, Andrew D; Hintermann, Edith; Christen, Urs

    2015-12-01

    Anti-CD3 therapy of type 1 diabetes results in a temporary halt of its pathogenesis but does not constitute a permanent cure. One problem is the reinfiltration of islets of Langerhans with regenerated, autoaggressive lymphocytes. We aimed at blocking such a reentry by neutralizing the key chemokine CXCL10. Combination therapy of diabetic RIP-LCMV and NOD mice with anti-CD3 and anti-CXCL10 antibodies caused a substantial remission of diabetes and was superior to monotherapy with anti-CD3 or anti-CXCL10 alone. The combination therapy prevented islet-specific T cells from reentering the islets of Langerhans and thereby blocked the autodestructive process. In addition, the local immune balance in the pancreas was shifted toward a regulatory phenotype. A sequential temporal inactivation of T cells and blockade of T-cell migration might constitute a novel therapy for patients with type 1 diabetes. PMID:26293506

  19. Anti-L-selectin antibody therapy does not worsen the postseptic course in a baboon model

    PubMed Central

    Redl, Heinz R; Martin, Ulrich; Khadem, Anna; Pelinka, Linda E; van Griensven, Martijn

    2005-01-01

    Introduction Anti-adhesion molecule therapy prevents leukocytes from extravasating. During exaggerated inflammation, this effect is wanted; however, during infection, blocking diapedesis may be detrimental. In this study, therefore, the potential risks of anti-L-selectin antibody therapy were evaluated in a primate model of sepsis. Methods Sixteen baboons were anesthetized and randomized into two groups. The experimental group received 2 mg/kg of the anti-L-selectin antibody HuDREG-55 and the control group received Ringer's solution prior to the onset of a 2 h infusion of Escherichia coli (1–2 × 109 colony forming units (CFU)/kg body weight). Serial blood samples were drawn over a 72 h period for the measurement of tumour necrosis factor-α, IL-6 and polymorphonuclear elastase. In addition, blood gas analysis, hematology and routine clinical chemistry were determined to monitor cardiovascular status, tissue perfusion and organ function. Results The three-day mortality rate and the mean survival time after E. coli-induced sepsis were similar in the two groups. The bacterial blood CFU levels were significantly higher in the placebo group than in the anti-L-selectin group. Other parameters measured throughout the 72 h experimental period, including the cardiovascular, immunologic, and hematologic responses as well as indicators of organ function and tissue perfusion, were similar in the two groups, with the exception of serum creatinine and mean arterial pressure at 32 h after E. coli challenge. Conclusion Anti-L-selectin therapy did not adversely affect survival, promote organ dysfunction or result in major side effects in the baboon sepsis model. Additionally, as anti-L-selectin therapy improved the bacterial clearance rate, it appears that this therapy is not detrimental during sepsis. This is in contrast to previous studies using the baboon model, in which antibody therapy used to block CD18 increased mortality. PMID:16356222

  20. Does bevacizumab impact anti-EGFR therapy efficacy in metastatic colorectal cancer?

    PubMed Central

    Boidot, Romain; Bengrine, Leila; Limagne, Emeric; Chevriaux, Angélique; Vincent, Julie; Ladoire, Sylvain; Apetoh, Lionel; Rébé, Cédric; Ghiringhelli, François

    2016-01-01

    Anti-EGFR therapy and antiangiogenic therapies are used alone or in combination with chemotherapies to improve survival in metastatic colorectal cancer. However, it is unknown whether pretreatment with antiangiogenic therapy could impact on the efficacy of anti-EGFR therapy. We selected one hundred and twenty eight patients diagnosed with advanced colorectal cancer with a KRAS and NRAS unmutated tumor. These patients were treated with cetuximab or panitumumab alone or with chemotherapy as second or third-line. Univariate and multivariate Cox model analysis were performed to estimate the effect of a previous bevacizumab regimen on progression free survival and on overall survival during anti-EGFR therapy. In vitro studies using wild type KRAS and NRAS colon cancer cells were performed to evaluate the impact of VEGF-A on cetuximab-induced cell death. The median progression free survival (PFS) during anti-EGFR treatment was significantly different between the bevacizumab group and the non-bevacizumab group (2.8 and 4 months respectively; p = 0.003). The median overall survival from the beginning of the metastatic disease was similar in the two groups (41.3 and 42 months respectively; p = 0.7). In vitro, VEGF-A induced a resistance toward cetuximab cytotoxicity on three KRAS and NRAS wild type colon cancer cell lines in a VEGFR2 and Stat-3-dependent manner. All in all, our clinical data, supported by in vitro procedures, suggest that a previous anti-VEGF therapy decreases anti-EGFR efficacy. Although these results are observed in a limited cohort, they could be taken into consideration for a better strategy of care for patient suffering from metastatic colorectal cancer. PMID:26824184

  1. Ustekinumab for the treatment of psoriasis.

    PubMed

    Laws, Philip M; Warren, Richard B

    2011-03-01

    Management of psoriasis over the last decade has changed significantly with the introduction of biological therapies. Ustekinumab is a first-in-class biological agent, inhibiting the action of IL-12 and IL-23, and has provided further evidence for the role of Th1 and Th17 lymphocytes in the pathogenesis of psoriasis. Efficacy has been clearly demonstrated in three Phase III clinical trials. Week 12 Psoriasis Area and Severity Index (PASI) 75 was observed in 66.4-75.7% of patients with PASI 90 achieved in 36.7-50.9%. This marked clinical response is also reflected in a significant improvement in quality of life. The most recent Phase III clinical trial has demonstrated the superior efficacy of ustekinumab (regardless of dosing regimen) compared with high-dose etanercept at week 12. Long-term efficacy has been demonstrated over 148 weeks with 64-76% of patients maintaining PASI 75. The role of ustekinumab in the treatment of psoriatic arthritis has shown some benefit in Phase II clinical trials. Phase III clinical trials are pending and will provide further guidance on management of concurrent disease. The currently available safety data are on the whole reassuring, although ongoing vigilance remains central to the detection of rare or late sequelae. PMID:21426253

  2. Anti-VEGF Therapy and the Retina: An Update

    PubMed Central

    Tah, Vikas; Orlans, Harry O.; Hyer, Jonathan; Casswell, Edward; Din, Nizar; Sri Shanmuganathan, Vishnu; Ramskold, Louise; Pasu, Saruban

    2015-01-01

    Ocular angiogenesis and macular oedema are major causes of sight loss across the world. Aberrant neovascularisation, which may arise secondary to numerous disease processes, can result in reduced vision as a result of oedema, haemorrhage, and scarring. The development of antivascular endothelial growth factor (anti-VEGF) agents has revolutionised the treatment of retinal vasogenic conditions. These drugs are now commonly employed for the treatment of a plethora of ocular pathologies including choroidal neovascularisation, diabetic macular oedema, and retinal vein occlusion to name a few. In this paper, we will explore the current use of anti-VEGF in a variety of retinal diseases and the impact that these medications have had on visual outcome for patients. PMID:26417453

  3. New Onset of Dermatomyositis/Polymyositis during Anti-TNF-α Therapies: A Systematic Literature Review

    PubMed Central

    Aberer, Werner; Massone, Cesare

    2014-01-01

    We performed a systematic search of databases from 1990 to 2013 to identify articles concerning the new onset of dermatomyositis/polymyositis (DM/PM) in patients treated with anti-TNF-α therapy. We retrieved 13 publications describing 20 patients where the new onset of DM/PM after anti-TNF-α therapy was recorded. 17 patients were affected by rheumatoid arthritis (RA), one by Crohn's disease, one by ankylosing spondilytis, and one by seronegative arthritis. In 91% of the cases antinuclear autoantibodies were detected after the introduction of anti-TNF-α therapy. In 6 patients antisynthetase antibodies were detected and other clinical findings as interstitial lung disease (ILD) were recorded. Improvement of DM/PM after anti-TNF suspension (with the concomitant use of other immunosuppressors) was recorded in 94% of cases. The emergence of DM/PM and antisynthetase syndrome seem to be associated with the use of anti-TNF-α agents, especially in patients with chronic inflammatory diseases (mainly RA) with positive autoantibodies before therapy initiation. In particular, physicians should pay attention to patients affected by RA with positive antisynthetase antibodies and/or history of ILD. In those cases, the use of the TNF-α blocking agents may trigger the onset of PM/DM or antisynthetase syndrome or may aggravate/trigger the lung disease. PMID:24600322

  4. In pursuit of new anti-angiogenic therapies for cancer treatment.

    PubMed

    Cai, Jun; Han, Song; Qing, Ruan; Liao, Daiqing; Law, Brian; Boulton, Michael E

    2011-01-01

    Despite advances in surgery, radiation therapy, and chemotherapy, patients with cancer have a poor prognosis. Sustained aberrant tumor angiogenesis and metastasis is a major obstacle for effective cancer treatment. Just a few years ago, few would argue that one of the key success stories of the modern cancer medicine were the anti-angiogenic drugs targeting the vascular endothelial growth factor (VEGF) signaling pathway approved by FDA. This initial success inspired many researchers to search for new anti-angiogenic targets and drugs with the hope that one day, anti-angiogenic therapy might really become the panacea for cancer patients. Unfortunately, the limited clinical benefits achieved with anti-angiogenic drugs conflicts with the widely accepted notion that angiogenesis is a key event in tumor progression. Emerging data indicate that unique characteristics of the tumor vasculature within the tumor microenvironment may hold the key for success of anti-angiogenic therapy. In particular, the molecular and cellular alterations that sustain aberrant tumor angiogenesis in the face of angiogenic inhibitors represents novel targets for rationally designing and improving current anti-angiogenic strategies. PMID:21196204

  5. Pharmacodynamics of TNF-α inhibitors in psoriasis.

    PubMed

    Vergou, Theognosia; Moustou, Aikaterini-Evangelia; Sfikakis, Petros P; Antoniou, Christina; Stratigos, Alexander J

    2011-07-01

    Over the last two decades, research developments have revolutionized our understanding of the pathogenesis of psoriasis and of the contribution of several cytokines in the manifestation of the disease. The key role of TNF-α in the pathogenesis of psoriasis has been extensively studied and its therapeutic action, initially observed in experimental models, has been clinically translated into therapeutic agents with remarkable efficacy in the treatment of the disease. There are currently two classes of marketed biologic drugs that reduce TNF-α bioavailability and are used clinically in psoriasis: the soluble TNF-α receptor-Fc fusion protein (etanercept) and the anti-TNF-α monoclonal antibodies (adalimumab and infliximab). The present article reviews the pharmacodynamic properties of the three TNF-α inhibitors and discusses possible differences in their mode of action, clinical efficacy and safety profile. PMID:22114860

  6. Clinical outcomes of anti-androgen withdrawal and subsequent alternative anti-androgen therapy for advanced prostate cancer following failure of initial maximum androgen blockade

    PubMed Central

    MOMOZONO, HIROYUKI; MIYAKE, HIDEAKI; TEI, HIROMOTO; HARADA, KEN-ICHI; FUJISAWA, MASATO

    2016-01-01

    The present study aimed to investigate the significance of anti-androgen withdrawal and/or subsequent alternative anti-androgen therapy in patients with advanced prostate cancer (PC) who relapsed after initial maximum androgen blockade (MAB). The present study evaluated the clinical outcomes of 272 consecutive advanced PC patients undergoing anti-androgen withdrawal and/or subsequent alternative anti-androgen therapy with flutamide following the failure of initial MAB using bicalutamide. With the exception of 41 patients (15.1%) who did not undergo anti-androgen withdrawal due to the characteristics of PC suggesting aggressive diseases, prostate-specific antigen (PSA) declined from the baseline value in 83 patients (35.9%), including 18 (7.8%) with PSA decline >50%, but not in the remaining 148 (64.1%). No significant difference in the overall survival (OS) or cancer-specific survival (CSS) among the three groups was observed based on the response to anti-androgen withdrawal. Following the introduction of alternative anti-androgen therapy with flutamide, PSA decline was observed in 185 patients (68.0%), including 103 (37.9%) who achieved a PSA reduction of >50%; however, the PSA level continued to elevate in the remaining 87 (32.0%). Furthermore, of the numerous factors examined, only the duration of the initial MAB therapy was shown to be significantly correlated with the PSA decline following alternative anti-androgen therapy. Multivariate analysis of several factors identified revealed that only PSA decline following alternative anti-androgen therapy was an independent predictor of CSS and OS. If initial MAB is effective, the introduction of alternative anti-androgen therapy may be considered; however, anti-androgen withdrawal should be omitted, irrespective of the characteristics of advanced PC. PMID:27123292

  7. Triptolide in the treatment of psoriasis and other immune-mediated inflammatory diseases.

    PubMed

    Han, Rui; Rostami-Yazdi, Martin; Gerdes, Sascha; Mrowietz, Ulrich

    2012-09-01

    Apart from cancer chronic (auto)immune-mediated diseases are a major threat for patients and a challenge for physicians. These conditions include classic autoimmune diseases like systemic lupus erythematosus, systemic sclerosis and dermatomyositis and also immune-mediated inflammatory diseases such as rheumatoid arthritis and psoriasis. Traditional therapies for these conditions include unspecific immunosuppressants including steroids and cyclophosphamide, more specific compounds such as ciclosporin or other drugs which are thought to act as immunomodulators (fumarates and intravenous immunoglobulins). With increasing knowledge about the underlying pathomechanisms of the diseases, targeted biologic therapies mainly consisting of anti-cytokine or anti-cytokine receptor agents have been developed. The latter have led to a substantial improvement of the induction of long term remission but drug costs are high and are not affordable in all countries. In China an extract of the herb Tripterygium wilfordii Hook F. (TwHF) is frequently used to treat autoimmune and/or inflammatory diseases due to its favourable cost-benefit ratio. Triptolide has turned out to be the active substance of TwHF extracts and has been shown to exert potent anti-inflammatory and immunosuppressive effects in vitro and in vivo. There is increasing evidence for an immunomodulatory and partly immunosuppressive mechanism of action of triptolide. Thus, compounds such as triptolide or triptolide derivatives may have the potential to be developed as a new class of drugs for these diseases. In this review we summarize the published knowledge regarding clinical use, pharmacokinetics and the possible mode of action of triptolide in the treatment of inflammatory diseases with a particular focus on psoriasis. PMID:22348323

  8. Sleep Loss and Cytokines Levels in an Experimental Model of Psoriasis

    PubMed Central

    Hirotsu, Camila; Rydlewski, Mariana; Araújo, Mariana Silva; Tufik, Sergio; Andersen, Monica Levy

    2012-01-01

    Up to 80% of people develop a cutaneous condition closely connected to their exposure to stressful life events. Psoriasis is a chronic recurrent inflammatory skin disorder with multifactorial etiology, including genetic background, environmental factors, and immune system disturbances with a strong cytokine component. Moreover, psoriasis is variably associated with sleep disturbance and sleep deprivation. This study evaluated the influence of sleep loss in the context of an animal model of psoriasis by measuring cytokine and stress-related hormone levels. Male adult Balb/C mice with or without psoriasis were subjected to 48 h of selective paradoxical sleep deprivation (PSD). Sleep deprivation potentiated the activities of kallikrein-5 and kallikrein-7 in the skin of psoriatic groups. Also, mice with psoriasis had significant increases in specific pro-inflammatory cytokines (IL-1β, IL-6 and IL-12) and decreases in the anti-inflammatory cytokine (IL-10) after PSD, which were normalized after 48 h of sleep rebound. Linear regression showed that IL-2, IL-6 and IL-12 levels predicted 66% of corticosterone levels, which were selectively increased in psoriasis mice subject to PSD. Kallikrein-5 was also correlated with pro-inflammatory cytokines, explaining 58% of IL-6 and IL-12 variability. These data suggest that sleep deprivation plays an important role in the exacerbation of psoriasis through modulation of the immune system in the epidermal barrier. Thus, sleep loss should be considered a risk factor for the development of psoriasis. PMID:23226485

  9. The role of drugs in the induction and/or exacerbation of psoriasis.

    PubMed

    Basavaraj, Kabbur Hanumanthappa; Ashok, Navya Mysore; Rashmi, Ramesh; Praveen, Thaggikuppe Krishnamurthy

    2010-12-01

    Psoriasis is a common skin disorder; knowledge of the factors that may induce, trigger, or exacerbate the disease is of primary importance in clinical practice. Drug intake is a major concern in this respect, as new drugs are constantly being added to the list of factors that may influence the course of this disease. Drug ingestion may result in exacerbation of pre-existing psoriasis, in induction of psoriatic lesions on clinically uninvolved skin in patients with psoriasis, or in precipitation of the disease in persons without family history of psoriasis or in predisposed individuals. In view of their relationship to drug-provoked psoriasis, therapeutic agents may be classified as drugs with strong evidence for a causal relationship to psoriasis, drugs about which there are considerable but insufficient data to support the induction or aggravation of the disease, and drugs that are occasionally reported to be associated with aggravation or induction. This review focuses on the most common causative agents for drug-induced, drug-triggered, or drug-aggravated psoriasis, such as β-blockers, lithium, synthetic antimalarial drugs, nonsteroidal anti-inflammatory agents, and tetracyclines, and the mechanisms of action of these drugs in the pathogenesis of psoriasis. PMID:21091671

  10. [Psoriasis and cardiovascular risk factors].

    PubMed

    Tal, Roy; Pavlovsky, Lev; David, Michael

    2012-10-01

    Psoriasis is a common inflammatory skin disease which may dramatically affect patients' lives. This chronic disease is characterized by a protracted course of alternating remissions and relapses. In recent years, the attention of researchers has focused on the association between psoriasis and cardiovascular disease risk factors. This review summarizes the literature on this topic with an emphasis on research conducted in Israel. PMID:23316664

  11. Varicella zoster meningitis complicating combined anti-tumor necrosis factor and corticosteroid therapy in Crohn's disease.

    PubMed

    Ma, Christopher; Walters, Brennan; Fedorak, Richard N

    2013-06-01

    Opportunistic viral infections are a well-recognized complication of anti-tumor necrosis factor (TNF) therapy for inflammatory bowel disease (IBD). Cases of severe or atypical varicella zoster virus infection, both primary and latent reactivation, have been described in association with immunosuppression of Crohn's disease (CD) patients. However, central nervous system varicella zoster virus infections have been rarely described, and there are no previous reports of varicella zoster virus meningitis associated with anti-TNF therapy among the CD population. Here, we present the case of a 40-year-old male with severe ileocecal-CD who developed a reactivation of dermatomal herpes zoster after treatment with prednisone and adalimumab. The reactivation presented as debilitating varicella zoster virus meningitis, which was not completely resolved despite aggressive antiviral therapy with prolonged intravenous acyclovir and subsequent oral valacyclovir. This is the first reported case of opportunistic central nervous system varicella zoster infection complicating anti-TNF therapy in the CD population. This paper also reviews the literature on varicella zoster virus infections of immunosuppressed IBD patients and the importance of vaccination prior to initiation of anti-TNF therapy. PMID:23745038

  12. Preclinical Assessment of the Efficacy of Anti-Angiogenic Therapies in Hepatocellular Carcinoma.

    PubMed

    Barral, Matthias; Raballand, Annemilaï; Dohan, Anthony; Soyer, Philippe; Pocard, Marc; Bonnin, Philippe

    2016-02-01

    Diffuse hepatocellular carcinoma (HCC) is a complex affliction in which comorbidities can bias global outcome of cancer therapy. Better methods are thus warranted to directly assess effects of therapy on tumor angiogenesis and growth. As tumor angiogenesis is invariably associated with changes in local blood flow, we assessed the utility of ultrasound imaging in evaluation of the efficacy of anti-angiogenic therapy in a spontaneous transgenic mouse model of HCC. Blood flow velocities were measured monthly in the celiac trunk before and after administration of sorafenib or bevacizumab at doses corresponding to those currently used in clinical practice. Concordant with clinical experience, sorafenib, but not bevacizumab, reduced microvascular density and suppressed tumor growth relative to controls. Evolution of blood flow velocities correlated with microvascular density and with the evolution of tumor size. Ultrasound imaging thus provides a useful non-invasive tool for preclinical evaluation of new anti-angiogenic therapies for HCC. PMID:26626491

  13. Exploring the Physiological Link between Psoriasis and Mood Disorders

    PubMed Central

    Connor, Cody J.; Liu, Vincent; Fiedorowicz, Jess G.

    2015-01-01

    Psoriasis is a chronic, immune-mediated skin condition with a high rate of psychiatric comorbidity, which often goes unrecognized. Beyond the negative consequences of mood disorders like depression and anxiety on patient quality of life, evidence suggests that these conditions can worsen the severity of psoriatic disease. The mechanisms behind this relationship are not entirely understood, but inflammation seems to be a key feature linking psoriasis with mood disorders, and physiologic modulators of this inflammation, including the hypothalamic-pituitary-adrenal axis and sympathetic nervous system, demonstrate changes with psychopathology that may be contributory. Cyclical disruptions in the secretion of the sleep hormone, melatonin, are also observed in both depression and psoriasis, and with well-recognized anti-inflammatory and antioxidant activity, this aberration may represent a shared contributor to both conditions as well as common comorbidities like diabetes and cardiovascular disease. While understanding the complexities of the biological mechanisms at play will be key in optimizing the management of patients with comorbid psoriasis and depression/anxiety, one thing is certain: recognition of psychiatric comorbidity is an imperative first step in effectively treating these patients as a whole. Evidence that improvement in mood decreases psoriasis severity underscores how psychological awareness can be critical to clinicians in their practice. PMID:26550011

  14. Exploring the Physiological Link between Psoriasis and Mood Disorders.

    PubMed

    Connor, Cody J; Liu, Vincent; Fiedorowicz, Jess G

    2015-01-01

    Psoriasis is a chronic, immune-mediated skin condition with a high rate of psychiatric comorbidity, which often goes unrecognized. Beyond the negative consequences of mood disorders like depression and anxiety on patient quality of life, evidence suggests that these conditions can worsen the severity of psoriatic disease. The mechanisms behind this relationship are not entirely understood, but inflammation seems to be a key feature linking psoriasis with mood disorders, and physiologic modulators of this inflammation, including the hypothalamic-pituitary-adrenal axis and sympathetic nervous system, demonstrate changes with psychopathology that may be contributory. Cyclical disruptions in the secretion of the sleep hormone, melatonin, are also observed in both depression and psoriasis, and with well-recognized anti-inflammatory and antioxidant activity, this aberration may represent a shared contributor to both conditions as well as common comorbidities like diabetes and cardiovascular disease. While understanding the complexities of the biological mechanisms at play will be key in optimizing the management of patients with comorbid psoriasis and depression/anxiety, one thing is certain: recognition of psychiatric comorbidity is an imperative first step in effectively treating these patients as a whole. Evidence that improvement in mood decreases psoriasis severity underscores how psychological awareness can be critical to clinicians in their practice. PMID:26550011

  15. [Cushing syndrome following external glucocorticoid administration in psoriasis].

    PubMed

    Dhein, S

    1986-02-01

    We report on a 20-year-old patient suffering from psoriasis vulgaris who treated himself with high dosages of powerful topical corticosteroids (250 mg desoxymethasone a week). He developed Cushing's syndrome which disappeared after discontinuation of that therapy. In general, these cases are rare because of the low percutaneous resorption of these glucocorticoids being below ten percent in most anatomical regions. PMID:3953135

  16. Anti-CD137 enhances anti-CD20 therapy of systemic B-cell lymphoma with altered immune homeostasis but negligible toxicity.

    PubMed

    Souza-Fonseca-Guimaraes, Fernando; Blake, Stephen J; Makkouk, Amani; Chester, Cariad; Kohrt, Holbrook E; Smyth, Mark J

    2016-07-01

    Studies of sequential anti-CD137/anti-CD20 therapy have previously shown that the efficacy of anti-CD20 was heavily reliant upon anti-CD137; however, the exact mechanism of the anti-B-cell lymphoma efficacy, and whether this correlates with enhanced adverse effects or toxicity, had not been elucidated. Here, we observed that sequential anti-CD137 administration with anti-CD20 resulted in a synergistic therapy, largely dependent upon Fc receptors (FcR), to prolong survival in an experimental B-cell lymphoma therapy model. Tumor suppression was accompanied by B cell depletion, which was not dependent on one activating FcR. Surprisingly, the B-cell activating factor (BAFF) was elevated in the plasma of mice receiving anti-CD137 alone or in combination with anti-CD20, while a selective increase in some plasma cytokines was also noted and triggered by anti-CD137. These effects were independent of activating FcR. Sustained treatment of advanced lymphoma revealed increased lymphocyte infiltrates into the liver and a significant decrease in the metabolic capability of the liver in mice receiving anti-CD137. Importantly, these effects were not exacerbated in mice receiving the anti-CD20/CD137 combination, and elevations in classical liver damage markers such as alanine aminotransferase (ALT) were less than that caused by the lymphoma itself. Thus, combined anti-CD20/anti-CD137 treatment increases the therapeutic index of anti-CD20 or anti-CD137 alone. These mouse data were corroborated by ongoing clinical development studies to assess safety, tolerability and pharmacodynamic activity of human patients treated by this approach. Together, these data support the use of this sequential antibody therapeutic strategy to improve the efficacy of rituximab in B-cell lymphoma patients. PMID:27622048

  17. The Distribution Patterns of Psoriasis

    PubMed Central

    Mitchell, J. C.

    1962-01-01

    Observation of the Koebner response was used in the clinical evaluation, determination of prognosis and management of seven patients with psoriasis. The Koebner response may be observed in patients with progressive and eruptive psoriasis; it is not the etiological factor but determines the localization of lesions when a psoriatic reaction is active. The eliciting stimuli for response are varied and non-specific; a common factor is cutaneous injury. Other skin diseases may provoke suitable eliciting cutaneous injury and determine the distribution patterns of sebo-psoriasis, psoriasis inversus, and psoriasiform neurodermatitis. Cutaneous injury is followed by repair or an attempt at repair. Psoriasis is a reaction pattern to non-specific stimuli in which psoriatic defect is brought to light by the increased rate of metabolism in cells regenerating after injury. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5 PMID:20327334

  18. Recognition of oxidized albumin and thyroid antigens by psoriasis autoantibodies

    PubMed Central

    Al-Shobaili, Hani A.; Ahmed, Ahmed A.; Rasheed, Zafar

    2015-01-01

    Objectives: To investigate the role of reactive-oxygen-species (ROS) induced epitopes on human-serum-albumin (HSA) and thyroid antigens in psoriasis autoimmunity. Methods: This study was performed in the College of Medicine, Qassim University, Buraidah, Saudi Arabia between May 2014 and February 2015. The study was designed to explore the role of ROS-induced epitopes in psoriasis autoimmunity. Singlet-oxygen (or ROS)-induced epitopes on protein (ROS-epitopes-albumin) was characterized by in-vitro and in-vivo. Thyroid antigens were prepared from rabbit thyroid, and thyroglobulin was isolated from thyroid extract. Immunocross-reactions of protein-A purified anti-ROS-epitopes-HSA-immunoglobulin G (IgGs) with thyroid antigen, thyroglobulin, and their oxidized forms were determined. Binding characteristics of autoantibodies in chronic plaque psoriasis patients (n=26) against ROS-epitopes-HSA and also with native and oxidized thyroid antigens were screened, and the results were compared with age-matched controls (n=22). Results: The anti-ROS-epitopes-HSA-IgGs showed cross-reactions with thyroid antigen, thyroglobulin and with their oxidized forms. High degree of specific binding by psoriasis IgGs to ROS-epitopes-HSA, ROS-thyroid antigen and ROS-thyroglobulin was observed. Immunoglobulin G from normal-human-controls showed negligible binding with all tested antigens. Moreover, sera from psoriasis patients had higher levels of carbonyl contents compared with control sera. Conclusion: Structural alterations in albumin, thyroid antigens by ROS, generate unique neo-epitopes that might be one of the factors for the induction of autoantibodies in psoriasis. PMID:26620982

  19. Gemella morbillorum Bacteremia after Anti-Tumor Necrosis Factor Alpha as Acne Inversa Therapy

    PubMed Central

    Vossen, Matthias G.; Gattringer, Klaus B.; Khalifeh, Neda; Koreny, Maria; Spertini, Verena; Mallouhi, Ammar; Willeit, Markus; Volc-Platzer, Beatrix; Asboth, Friederike; Graninger, Wolfgang; Thalhammer, Florian

    2012-01-01

    We present a case of fever, brain abscesses, and Gemella morbillorum bacteremia after anti-tumor necrosis factor alpha (TNF-α) therapy in a 21-year-old acne inversa patient currently taking long-term dapsone. To the best of our knowledge, this is the first report describing such a case. During antimicrobial therapy, the patient developed systemic varicella infection with severe thrombocytopenia. PMID:22189120

  20. Psoriasis, a model of dermatologic psychosomatic disease: psychiatric implications and treatments.

    PubMed

    Rieder, Evan; Tausk, Francisco

    2012-01-01

    Psoriasis is a common dermatologic disorder with psychiatric comorbidity that often goes undetected and untreated. Psoriasis has higher associations with psychiatric illness than do other dermatologic conditions. We conducted a comprehensive qualitative review of all published medical literature on psoriasis and psychiatric comorbidities since 2005. We found that psoriasis patients suffer psychiatric and psychosocial morbidity that is not commensurate with the extent of cutaneous lesions. Biologic therapies and nonpharmacologic psychosocial interventions show promise in treating comorbid psychiatric illness. The main limitations of this review are the low quality of published studies and the infrequent use of basic science endpoints in reporting treatment outcomes. The literature examining the psychiatric comorbidity of psoriasis is expanding but remains of variable quality. Stronger studies will be necessary to more accurately estimate comorbidities and help identify and comprehensively treat suffering patients. PMID:22182372

  1. Maximizing patient adherence for optimal outcomes in psoriasis.

    PubMed

    Bewley, A; Page, B

    2011-06-01

    Psoriasis is a chronic, disabling disease in which adherence to treatment is often poor. The aim of this article is to highlight the problem of adherence to long-term treatment in psoriasis and the factors that contribute to it, and to discuss how adherence, and thus outcomes, can be improved. This article is based on a presentation given by the authors at a satellite symposium held during the 19th Congress of the European Academy of Dermatology and Venereology, 6-10 October, 2010, in Gothenburg, Sweden. Adherence to topical medication is a major problem in psoriasis. Not only are prescriptions not being filled by patients (primary adherence) but topical medications are not being used as recommended (secondary adherence). The issue is complex due to the many factors which affect adherence, including efficacy, ease of use and convenience of application, and the healthcare professional-patient relationship. Due to the nature of the disease, patients suffer poor self-image and feel stigmatized, particularly when psoriasis is present on a visible part of the body. Consequently, the negative impact of psoriasis on patient quality of life underlies many adherence issues. It is therefore important for treatment to address the psychological aspects as well as the physical symptoms of psoriasis. Improvements in several areas of disease management may lead to benefits in medication adherence and hence clinical benefit. Prescribing therapy in line with patient preference for treatment vehicle and improving the healthcare professional-patient relationship may be key factors. Nurses have an important role in educating patients and delivering long-term care. This individualized, personal, approach may help improve treatment adherence, outcomes, and the quality of life for patients with psoriasis. PMID:21507078

  2. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 5. Guidelines of care for the treatment of psoriasis with phototherapy and photochemotherapy.

    PubMed

    Menter, Alan; Korman, Neil J; Elmets, Craig A; Feldman, Steven R; Gelfand, Joel M; Gordon, Kenneth B; Gottlieb, Alice; Koo, John Y M; Lebwohl, Mark; Lim, Henry W; Van Voorhees, Abby S; Beutner, Karl R; Bhushan, Reva

    2010-01-01

    Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this fifth of 6 sections of the guidelines of care for psoriasis, we discuss the use of ultraviolet (UV) light therapy for the treatment of patients with psoriasis. Treatment should be tailored to meet individual patients' needs. We will discuss in detail the efficacy and safety as well as offer recommendations for the use of phototherapy, including narrowband and broadband UVB and photochemotherapy using psoralen plus UVA, alone and in combination with topical and systemic agents. We will also discuss the available data for the use of the excimer laser in the targeted treatment of psoriasis. Finally, where available, we will summarize the available data that compare the safety and efficacy of the different forms of UV light therapy. PMID:19811850

  3. Combination therapy with anti-CTLA4 and anti-PD1 leads to distinct immunologic changes in-vivo

    PubMed Central

    Das, Rituparna; Verma, Rakesh; Sznol, Mario; Boddupalli, Chandra Sekhar; Gettinger, Scott N.; Kluger, Harriet; Callahan, Margaret; Wolchok, Jedd D; Halaban, Ruth; Dhodapkar, Madhav V.; Dhodapkar, Kavita M.

    2014-01-01

    Combination therapy concurrently targeting PD1 and CTLA4 immune checkpoints leads to remarkable anti-tumor effects. While both PD1 and CTLA4 dampen the T cell activation, the in vivo effects of these drugs in humans remain to be clearly defined. In order to better understand biologic effects of therapy, we analyzed blood/tumor tissue from 45 patients undergoing single or combination immune checkpoint blockade. We show that blockade of CTLA4, PD1 or combination of the two leads to distinct genomic and functional signatures in vivo in purified human T cells and monocytes. Therapy-induced changes are more prominent in T cells than in monocytes and involve largely non-overlapping changes in coding genes including alternatively-spliced transcripts, and non-coding RNAs. Pathway analysis revealed that CTLA4-blockade induces a proliferative signature predominantly in a subset of transitional memory T cells, while PD1-blockade instead leads to changes in genes implicated in cytolysis and natural killer cell function. Combination blockade leads to non-overlapping changes in gene expression including proliferation-associated and chemokine genes. These therapies also have differential effects on plasma levels of CXCL10, sIL2R and IL1α. Importantly, PD1 receptor occupancy following anti-PD1 therapy may be incomplete in the tumor T cells even in the setting of complete receptor occupancy in circulating T cells. These data demonstrate that in spite of shared property of checkpoint blockade, antibodies against PD1, CTLA4 alone or in combination have distinct immunologic effects in vivo. Improved understanding of pharmacodynamic effects of these agentsin patients will support rational development of immune-based combinations against cancer. PMID:25539810

  4. Combination anti-CD137 and anti-CD40 antibody therapy in murine myc-driven hematological cancers.

    PubMed

    Westwood, Jennifer A; Matthews, Geoffrey M; Shortt, Jake; Faulkner, David; Pegram, Hollie J; Duong, Connie P M; Chesi, Marta; Bergsagel, P Leif; Sharp, Leslie L; Huhn, Richard D; Darcy, Phillip K; Johnstone, Ricky W; Kershaw, Michael H

    2014-08-01

    In order to stimulate antigen presentation and T cell activity against cancer, we treated three different tumor models in mice with the monoclonal antibodies anti-CD40 plus anti-CD137 (BiMab). In a subcutaneous transplantable MC38 colon cancer model, there was significant enhancement in the survival of mice following BiMab treatment. Anti-CD40 has shown considerable success against lymphoma in previous studies by other investigators, and we also showed in this study that, in a model of Eμ-Myc lymphoma, there was a statistically significant enhancement of survival of mice following BiMab treatment. Following the success of the BiMab treatment in the previous two models, we wished to determine if it would be successful in a mouse model of multiple myeloma. Firstly, we tested a transplantable model of disease in which multiple myeloma cells derived from Vk*MYC mice were injected intravenously. A minor proportion of anti-CD137 and BiMab treated mice experienced prolongation of life beyond 250 days. Then we tested the therapy in a spontaneously occurring multiple myeloma model, in Vk*MYC transgenic mice. The majority of mice treated survived longer than control mice, although statistical significance was not demonstrated. PMID:24934848

  5. Impact of efalizumab on patient-reported outcomes in high-need psoriasis patients: results of the international, randomized, placebo-controlled Phase III Clinical Experience Acquired with Raptiva (CLEAR) trial [NCT00256139

    PubMed Central

    Ortonne, Jean-Paul; Shear, Neil; Shumack, Stephen; Henninger, Eric

    2005-01-01

    Background Chronic psoriasis can negatively affect patients' lives. Assessing the impact of treatment on different aspects of a patient's health-related quality of life (HRQOL) is therefore important and relevant in trials of anti-psoriasis agents. The recombinant humanized IgG1 monoclonal antibody efalizumab targets multiple T-cell-dependent steps in the immunopathogenesis of psoriasis. Efalizumab has demonstrated safety and efficacy in several clinical trials, and improves patients' quality of life. Objective: To evaluate the impact of efalizumab on HRQOL and other patient-reported outcomes in patients with moderate to severe plaque psoriasis, including a large cohort of High-Need patients for whom at least 2 other systemic therapies were unsuitable because of lack of efficacy, intolerance, or contraindication. Methods A total of 793 patients were randomized in a 2:1 ratio to receive efalizumab 1 mg/kg/wk (n = 529) or placebo (n = 264) for 12 weeks. The study population included 526 High-Need patients (342 efalizumab, 184 placebo). The treatment was evaluated by patients using the HRQOL assessment tools Short Form-36 (SF-36) and Dermatology Life Quality Index (DLQI). Other patient-reported assessments included the Psoriasis Symptom Assessment (PSA), a visual analog scale (VAS) for itching, and the Patient's Global Psoriasis Assessment (PGPA). Results Efalizumab was associated with improvements at Week 12 from baseline in patient-reported outcomes, both in the total study population and in the High-Need cohort. Among all efalizumab-treated patients, the DLQI improved by 5.7 points from baseline to Week 12, relative to an improvement of 2.3 points for placebo patients (P < .001). Corresponding improvements in DLQI in the High-Need cohort were 5.4 points for efalizumab compared to 2.3 for placebo (P < .001). Improvements from baseline on the SF-36, PSA, PGPA, and itching VAS at Week 12 were also significantly greater in efalizumab-treated patients than for placebo

  6. Is the Ratio of Antibodies Against Oxidized LDL to Oxidized LDL an Indicator of Cardiovascular Risk in Psoriasis?

    PubMed Central

    Rajappa, Medha; Mohan Thappa, Devinder; Chandrashekar, Laxmisha; Munisamy, Malathi; Revathy, G.

    2016-01-01

    Objectives Psoriasis is a chronic inflammatory skin disease. Chronic inflammation results in increased oxidative stress and oxidizes lipoproteins, increasing their atherogenicity. This study sought to estimate the levels of oxidized low-density lipoprotein (ox-LDL) and antibodies against oxidized LDL (anti-ox-LDL) and compute the ratio of anti-ox-LDL/ox-LDL as a single composite parameter to assess the oxidative lipoprotein burden as an indicator of cardiovascular risk in patients with psoriasis. Methods This cross-sectional study included 45 patients with psoriasis. All patients were given a psoriasis severity index score and their ox-LDL and anti-ox-LDL estimated using ELISA. Results The results of this study show an elevation in the ratio of anti-ox-LDL to ox-LDL in patients with psoriasis, which initiate and perpetuate the pathogenesis of psoriasis and its comorbidity, atherosclerotic cardiovascular disease. Conclusions Our results suggest that an elevated ratio of anti-ox-LDL/ox-LDL can serve as a composite parameter reflecting the total oxidative lipoprotein burden and cardiovascular risk in psoriasis patients. PMID:27602197

  7. Treatment of psoriasis with etanercept: the typical patient profile.

    PubMed

    Prinz, J C; Puig, L; Girolomoni, G

    2016-07-01

    The chronic nature of psoriasis means that patients often require lifetime treatment. Over this time, treatment frequently has to be adapted to meet variable demands resulting from changes in life course and life events. Biological drugs used to treat psoriasis vary in their dosing regimens, convenience and flexibility. Dermatologists need to understand which biologic agent is best suited for each individual patient. A wealth of evidence supports the safe and effective use of etanercept, which offers a rapid and sustained response, flexibility of dosing, maintenance of response after dose reduction or interruption, and efficacy against non-skin manifestations such as psoriatic arthritis. An expert panel met to agree the typical patient profile of a psoriasis patient treated with etanercept, the main benefits of etanercept in psoriasis, and the patient group most likely to benefit from its use. They agreed that flexibility of dosing, the potential to individualize therapy by stopping and starting treatment while maintaining efficacy, and the possibility of cost saving through the use of flexible treatment regimens were important benefits supporting the use of etanercept in many patients with psoriasis. PMID:27073046

  8. Improving therapeutic activity of anti-CD20 antibody therapy through immunomodulation in lymphoid malignancies.

    PubMed

    Lipowska-Bhalla, Grazyna; Fagnano, Ester; Illidge, Timothy M; Cheadle, Eleanor J

    2016-06-01

    Nearly two decades ago rituximab heralded a new era in management of B cell malignancies significantly increasing response rates and survival. However, despite clear therapeutic advantage, significant numbers of patients become refractory to anti-CD20 mAb therapy, suggesting urgent improvements are required. It is now well recognized that the suppressive tumor microenvironment plays an important role in the outcome of anti-CD20 mAb therapy and that manipulation of this environment may improve the efficacy and produce long-term tumor control. The past few years have seen a surge of interest in immunomodulatory agents capable of overwriting immune suppressive networks into favorable clinical outcome. Currently, a number of such combinations with anti-CD20 mAb is under evaluation and some have produced encouraging outcomes in rituximab refractory disease. In this review, we give an outline of anti-CD20 mAbs and explore the combinations with immunomodulatory agents that enhance antitumor immunity through targeting stimulatory or inhibitory pathways and have proven potential to synergize with anti-CD20 mAb therapy. These agents, primarily mAbs, target CTLA-4, PD-1/PD-L1, and CD40. PMID:27050042

  9. Ocular anti-VEGF therapy for diabetic retinopathy: overview of clinical efficacy and evolving applications.

    PubMed

    Cheung, Ning; Wong, Ian Y; Wong, Tien Y

    2014-04-01

    Ocular anti-vascular endothelial growth factor (VEGF) therapy represents one of the most significant advances in modern medicine. The introduction and widespread use of ocular anti-VEGF therapy for age-related macular degeneration heralded a new era in the treatment of vascular and exudative diseases of the retina. Its expanding indications now include diabetic macular edema and proliferative diabetic retinopathy, two vision-threatening forms of diabetic retinopathy. It is widely anticipated that ocular anti-VEGF therapy could spark a dramatic shift in the treatment paradigm for diabetic retinopathy. However, despite its clear efficacy shown in clinical trials, the dynamic landscape of evolving medical, ethical, and economic issues related to this new treatment suggests significant challenges ahead. In this article, we provide a discussion of this topic as part of this two-part Bench to Clinic narrative. Here, our Clinic contribution provides an overview of the current evidence from clinical trials on anti-VEGF therapy for diabetic retinopathy, and highlights the hopes and fears of this new treatment from clinical and public health standpoints. In the Bench narrative that precedes this contribution, Simó et al. provide an overview of the role of VEGF in the pathogenesis of diabetic retinopathy. PMID:24652721

  10. Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review

    PubMed Central

    Yang, Shiqi; Zhao, Jingke; Sun, Xiaodong

    2016-01-01

    As a progressive chronic disease, age-related macular degeneration (AMD) is the leading cause of irreversible vision impairment worldwide. Experimental and clinical evidence has demonstrated that vascular endothelial growth factor (VEGF) plays a vital role in the formation of choroidal neovascularization. Intravitreal injections of anti-VEGF agents have been recommended as a first-line treatment for neovascular AMD. However, persistent fluid or recurrent exudation still occurs despite standardized anti-VEGF therapy. Patients suffering from refractory or recurrent neovascular AMD may develop mechanisms of resistance to anti-VEGF therapy, which results in a diminished therapeutic effect. Until now, there has been no consensus on the definitions of refractory neovascular AMD and recurrent neovascular AMD. This article aims at clarifying these concepts to evaluate the efficacy of switching drugs, which contributes to making clinical decision more scientifically. Furthermore, insight into the causes of resistance to anti-VEGF therapy would be helpful for developing possible therapeutic approaches, such as combination therapy and multi-target treatment that can overcome this resistance. PMID:27330279

  11. Bilirubin Nanoparticles as a Nanomedicine for Anti-inflammation Therapy.

    PubMed

    Lee, Yonghyun; Kim, Hyungjun; Kang, Sukmo; Lee, Jinju; Park, Jinho; Jon, Sangyong

    2016-06-20

    Despite the high potency of bilirubin as an endogenous anti-inflammatory compound, its clinical translation has been hampered because of its insolubility in water. Bilirubin-based nanoparticles that may overcome this critical issue are presented. A polyethylene glycol compound (PEG) was covalently attached to bilirubin, yielding PEGylated bilirubin (PEG-BR). The PEG-BR self-assembled into nanoscale particles with a size of approximately 110 nm, termed bilirubin nanoparticles (BRNPs). BRNPs are highly efficient hydrogen peroxide scavengers, thereby protecting cells from H2 O2 -induced cytotoxicity. In a murine model of ulcerative colitis, intravenous injection of BRNPs showed preferential accumulation of nanoparticles at the sites of inflammation and significantly inhibited the progression of acute inflammation in the colon. Taken together, BRNPs show potential for use as a therapeutic nanomedicine in various inflammatory diseases. PMID:27144463

  12. Comparative Safety and Tolerability of Anti-VEGF therapy in Age-Related Macular Degeneration

    PubMed Central

    Modi, Yasha S.; Tanchon, Carley; Ehlers, Justis P

    2015-01-01

    Neovascular age-related macular degeneration (NVAMD) is one of the leading causes of blindness. Over the last decade, the treatment of NVAMD has been revolutionized by the development intravitreal anti-vascular endothelial growth factor (VEGF) therapies. Several anti-VEGF medications are used for the treatment of NVAMD. The safety and tolerability of these medications deserve review given the high prevalence of NVAMD and the significant utilization of these medications. Numerous large randomized clinical trials have not shown any definitive differential safety relative to ocular or systemic safety of these medications. Intravitreal anti-VEGF therapy does appear to impact systemic VEGF levels, but the implications of these changes remain unclear. One unique safety concern relates drug compounding and the potential risks of contamination, specifically for bevacizumab. Continued surveillance for systemic safety concerns, particularly for rare events is merited. Overall these medications are well tolerated and effective in the treatment of NVAMD. PMID:25700714

  13. Dry powder inhalable formulations for anti-tubercular therapy.

    PubMed

    Parumasivam, Thaigarajan; Chang, Rachel Yoon Kyung; Abdelghany, Sharif; Ye, Tian Tian; Britton, Warwick John; Chan, Hak-Kim

    2016-07-01

    Tuberculosis (TB) is an intracellular infectious disease caused by the airborne bacterium, Mycobacterium tuberculosis. Despite considerable research efforts, the treatment of TB continues to be a great challenge in part due to the requirement of prolonged therapy with multiple high-dose drugs and associated side effects. The delivery of pharmacological agents directly to the respiratory system, following the natural route of infection, represents a logical therapeutic approach for treatment or vaccination against TB. Pulmonary delivery is non-invasive, avoids first-pass metabolism in the liver and enables targeting of therapeutic agents to the infection site. Inhaled delivery also potentially reduces the dose requirement and the accompanying side effects. Dry powder is a stable formulation of drug that can be stored without refrigeration compared to liquids and suspensions. The dry powder inhalers are easy to use and suitable for high-dose formulations. This review focuses on the current innovations of inhalable dry powder formulations of drug and vaccine delivery for TB, including the powder production method, preclinical and clinical evaluations of inhaled dry powder over the last decade. Finally, the risks associated with pulmonary therapy are addressed. A novel dry powder formulation with high percentages of respirable particles coupled with a cost effective inhaler device is an appealing platform for TB drug delivery. PMID:27212477

  14. An Expert's Advice: What To Do If You Have Psoriasis

    MedlinePlus

    ... on. Feature: Living with Psoriasis An Expert's Advice: What To Do If You Have Psoriasis Past Issues / ... the Dermatology Foundation, and the American Skin Association. What is psoriasis? Psoriasis is a chronic (long-term) ...

  15. What is Psoriasis? | NIH MedlinePlus the Magazine

    MedlinePlus

    ... page please turn Javascript on. Feature: Living with Psoriasis What is Psoriasis? Past Issues / Fall 2013 Table of Contents What Is Psoriasis? There are several forms of psoriasis. The typical ...

  16. I Live with Psoriasis | NIH MedlinePlus the Magazine

    MedlinePlus

    ... page please turn Javascript on. Feature: Living with Psoriasis I Live with Psoriasis Past Issues / Fall 2013 Table of Contents Kristin ... equally. "Know as much as you can about psoriasis..." —Kristin Donahue Psoriasis first flared into Kristin Donahue's ...

  17. Anti-oxidative therapy with oral dapsone improved HCV antibody positive annular elastolytic giant cell granuloma.

    PubMed

    Igawa, K; Maruyama, R; Katayama, I; Nishioka, K

    1997-05-01

    A 72-year-old fisherman who was positive for the HCV antibody developed an annular, erythematous, infiltrated lesions on sun-exposed areas. The lesions were diagnosed as annular elastolytic giant cell granuloma both clinically and histologically. Topical corticosteroid and cryotherapy with liquid nitrogen for several months failed to improve the lesions. We then started dapsone, a known anti-oxidant, at 50 mg/day. A month later, the margins of the erythematous lesions faded, and the infiltration gradually decreased. No recurrence has been observed for one year after the start of the therapy. Anti-oxidative therapy appears to be effective for annular elastolytic giant cell granuloma and could be an alternate therapy for refractory granulomatous disease. PMID:9198323

  18. Evolution of acquired resistance to anti-cancer therapy

    PubMed Central

    Foo, Jasmine; Michor, Franziska

    2014-01-01

    Acquired drug resistance is a major limitation for the successful treatment of cancer. Resistance can emerge due to a variety of reasons including host environmental factors as well as genetic or epigenetic alterations in the cancer cells. Evolutionary theory has contributed to the understanding of the dynamics of resistance mutations in a cancer cell population, the risk of resistance pre-existing before the initiation of therapy, the composition of drug cocktails necessary to prevent the emergence of resistance, and optimum drug administration schedules for patient populations at risk of evolving acquired resistance. Here we review recent advances towards elucidating the evolutionary dynamics of acquired drug resistance and outline how evolutionary thinking can contribute to outstanding questions in the field. PMID:24681298

  19. Anti-VEGF therapy for diabetic macular edema.

    PubMed

    Stewart, Michael W

    2014-08-01

    Vascular endothelial growth factor (VEGF) plays a pivotal role in the development of diabetic macular edema (DME), the leading cause of vision loss among working-aged individuals. A decade of clinical trials demonstrated that drugs that bind soluble VEGF restore the integrity of the blood-retinal barrier, resolve macular edema, and improve vision in most patients with DME. Four drugs (pegaptanib, ranibizumab, bevacizumab, and aflibercept) effectively treat DME when administered by intravitreal injections. Only ranibizumab has received U.S. Food and Drug Administration (FDA) approval for DME, but bevacizumab is commonly used off-label, and an FDA application for aflibercept is pending. Effective treatment requires repeated injections, although recent data suggest that the treatment burden diminishes after 1 year. Intravitreal therapy is generally safe, although the incidence of systemic thromboembolic events varies among trials. PMID:24919750

  20. Optical imaging predicts tumor response to anti-EGFR therapy

    PubMed Central

    Helman, Emily E; Newman, J Robert; Dean, Nichole R; Zhang, Wenyue; Zinn, Kurt R

    2010-01-01

    To evaluate cetuximab treatment in head and neck squamous cell carcinoma xenografts and cell lines, we investigated a preclinical model of head and neck squamous cell carcinoma. Head and neck squamous cell carcinoma cell lines SCC-1, FaDu, CAL27, UM-SCC-5 and UM-SCC-22A were used to generate subcutaneous flank xenografts in SCID mice. Mice were divided into control and cetuximab treatment groups, mice in the latter group received 250 µg cetuximab once weekly for four weeks. After completion of therapy, SCC-1 (p < 0.001), UM-SCC-5 (p < 0.001), UM-SCC-22A (p = 0.016) and FaDu (p = 0.007) tumors were significantly smaller than control, while CAL27 tumors were not different from controls (p = 0.90). Mice were systemically injected with 50 µg of the Cy5.5-cetuximab bioconjugate and imaged by stereomicroscopy to determine if tumor fluorescence predicted tumor response. Intact tumor fluorescence did not predict response. Tissue was harvested from untreated xenografts to evaluate ex vivo imaging. Cell lines were then evaluated in vitro for fluorescence imaging after Cy5.5-cetuximab bioconjugate labeling. The location of fluorescence observed in labeled cells was significantly different for cell lines that responded to treatment, relative to unresponsive cells. Tumors from cell lines that showed low internalized signal in vitro responded best to treatment with cetuximab. This preclinical model may aid in determining which cancer patients are best suited for cetuximab therapy. PMID:20505368

  1. Development of HIV vectors for anti-HIV gene therapy.

    PubMed Central

    Poeschla, E; Corbeau, P; Wong-Staal, F

    1996-01-01

    Current gene therapy protocols for HIV infection use transfection or murine retrovirus mediated transfer of antiviral genes into CD4+ T cells or CD34+ progenitor cells ex vivo, followed by infusion of the gene altered cells into autologous or syngeneic/allogeneic recipients. While these studies are essential for safety and feasibility testing, several limitations remain: long-term reconstitution of the immune system is not effected for lack of access to the macrophage reservoir or the pluripotent stem cell population, which is usually quiescent, and ex vivo manipulation of the target cells will be too expensive and impractical for global application. In these regards, the lentivirus-specific biologic properties of the HIVs, which underlie their pathogenetic mechanisms, are also advantageous as vectors for gene therapy. The ability of HIV to specifically target CD4+ cells, as well as non-cycling cells, makes it a promising candidate for in vivo gene transfer vector on one hand, and for transduction of non-cycling stem cells on the other. Here we report the use of replication-defective vectors and stable vector packaging cell lines derived from both HIV-1 and HIV-2. Both HIV envelopes and vesicular stomatitis virus glycoprotein G were effective in mediating high-titer gene transfer, and an HIV-2 vector could be cross-packaged by HIV-1. Both HIV-1 and HIV-2 vectors were able to transduce primary human macrophages, a property not shared by murine retroviruses. Vesicular stomatitis virus glycoprotein G-pseudotyped HIV vectors have the potential to mediate gene transfer into non-cycling hematopoietic stem cells. If so, HIV or other lentivirus-based vectors will have applications beyond HIV infection. Images Fig. 1 PMID:8876146

  2. Structural and Physical Basis for Anti-IgE Therapy

    NASA Astrophysics Data System (ADS)

    Wright, Jon D.; Chu, Hsing-Mao; Huang, Chun-Hsiang; Ma, Che; Wen Chang, Tse; Lim, Carmay

    2015-06-01

    Omalizumab, an anti-IgE antibody, used to treat severe allergic asthma and chronic idiopathic urticaria, binds to IgE in blood or membrane-bound on B lymphocytes but not to IgE bound to its high (FcɛRI) or low (CD23) affinity receptor. Mutagenesis studies indicate overlapping FcɛRI and omalizumab-binding sites in the Cɛ3 domain, but crystallographic studies show FcɛRI and CD23-binding sites that are far apart, so how can omalizumab block IgE from binding both receptors? We report a 2.42-Å omalizumab-Fab structure, a docked IgE-Fc/omalizumab-Fab structure consistent with available experimental data, and the free energy contributions of IgE residues to binding omalizumab, CD23, and FcɛRI. These results provide a structural and physical basis as to why omalizumab cannot bind receptor-bound IgE and why omalizumab-bound IgE cannot bind to CD23/FcɛRI. They reveal the key IgE residues and their roles in binding omalizumab, CD23, and FcɛRI.

  3. Structural and Physical Basis for Anti-IgE Therapy

    PubMed Central

    Wright, Jon D.; Chu, Hsing-Mao; Huang, Chun-Hsiang; Ma, Che; Wen Chang, Tse; Lim, Carmay

    2015-01-01

    Omalizumab, an anti-IgE antibody, used to treat severe allergic asthma and chronic idiopathic urticaria, binds to IgE in blood or membrane-bound on B lymphocytes but not to IgE bound to its high (FcεRI) or low (CD23) affinity receptor. Mutagenesis studies indicate overlapping FcεRI and omalizumab-binding sites in the Cε3 domain, but crystallographic studies show FcεRI and CD23-binding sites that are far apart, so how can omalizumab block IgE from binding both receptors? We report a 2.42-Å omalizumab-Fab structure, a docked IgE-Fc/omalizumab-Fab structure consistent with available experimental data, and the free energy contributions of IgE residues to binding omalizumab, CD23, and FcεRI. These results provide a structural and physical basis as to why omalizumab cannot bind receptor-bound IgE and why omalizumab-bound IgE cannot bind to CD23/FcεRI. They reveal the key IgE residues and their roles in binding omalizumab, CD23, and FcεRI. PMID:26113483

  4. Human anti-nucleolin recombinant immunoagent for cancer therapy.

    PubMed

    Palmieri, Dario; Richmond, Timothy; Piovan, Claudia; Sheetz, Tyler; Zanesi, Nicola; Troise, Fulvia; James, Cindy; Wernicke, Dorothee; Nyei, Fata; Gordon, Timothy J; Consiglio, Jessica; Salvatore, Francesco; Coppola, Vincenzo; Pichiorri, Flavia; De Lorenzo, Claudia; Croce, Carlo M

    2015-07-28

    Nucleolin (NCL) is a nucleocytoplasmic protein involved in many biological processes, such as ribosomal assembly, rRNA processing, and mRNA stabilization. NCL also regulates the biogenesis of specific microRNAs (miRNAs) involved in tumor development and aggressiveness. Interestingly, NCL is expressed on the surface of actively proliferating cancer cells, but not on their normal counterparts. Therefore, NCL is an attractive target for antineoplastic treatments. Taking advantage of phage-display technology, we engineered a fully human single-chain fragment variable, named 4LB5. This immunoagent binds NCL on the cell surface, it is translocated into the cytoplasm of target cells, and it abrogates the biogenesis of NCL-dependent miRNAs. Binding of 4LB5 to NCL on the cell surface of a variety of breast cancer and hepatocellular carcinoma cell lines, but not to normal-like MCF-10a breast cells, dramatically reduces cancer cell viability and proliferation. Finally, in orthotopic breast cancer mouse models, 4LB5 administration results in a significant reduction of the tumor volume without evident side effects. In summary, here we describe, to our knowledge, the first anti-NCL single-chain fragment variable displaying antineoplastic activity against established solid tumors, which could represent the prototype of novel immune-based NCL-targeting drugs with clinical potential as diagnostic and therapeutic tools in a wide variety of human cancers. PMID:26170308

  5. Human anti-nucleolin recombinant immunoagent for cancer therapy

    PubMed Central

    Palmieri, Dario; Richmond, Timothy; Piovan, Claudia; Sheetz, Tyler; Zanesi, Nicola; Troise, Fulvia; James, Cindy; Wernicke, Dorothee; Nyei, Fata; Gordon, Timothy J.; Consiglio, Jessica; Salvatore, Francesco; Coppola, Vincenzo; Pichiorri, Flavia; De Lorenzo, Claudia; Croce, Carlo M.

    2015-01-01

    Nucleolin (NCL) is a nucleocytoplasmic protein involved in many biological processes, such as ribosomal assembly, rRNA processing, and mRNA stabilization. NCL also regulates the biogenesis of specific microRNAs (miRNAs) involved in tumor development and aggressiveness. Interestingly, NCL is expressed on the surface of actively proliferating cancer cells, but not on their normal counterparts. Therefore, NCL is an attractive target for antineoplastic treatments. Taking advantage of phage-display technology, we engineered a fully human single-chain fragment variable, named 4LB5. This immunoagent binds NCL on the cell surface, it is translocated into the cytoplasm of target cells, and it abrogates the biogenesis of NCL-dependent miRNAs. Binding of 4LB5 to NCL on the cell surface of a variety of breast cancer and hepatocellular carcinoma cell lines, but not to normal-like MCF-10a breast cells, dramatically reduces cancer cell viability and proliferation. Finally, in orthotopic breast cancer mouse models, 4LB5 administration results in a significant reduction of the tumor volume without evident side effects. In summary, here we describe, to our knowledge, the first anti-NCL single-chain fragment variable displaying antineoplastic activity against established solid tumors, which could represent the prototype of novel immune-based NCL-targeting drugs with clinical potential as diagnostic and therapeutic tools in a wide variety of human cancers. PMID:26170308

  6. Childhood psoriasis: often favorable outcome.

    PubMed

    2009-12-01

    (1) Plaque psoriasis is the most common form of psoriasis in children. Topical agents should be tried first, especially well-tolerated products such as emollients. Topical corticosteroids are sometimes useful during exacerbations but, given adverse effects, they should only be used for short periods; (2) UVB phototherapy is an option for extensive psoriasis refractory to local treatments, but it carries a long-term risk of skin cancer. Immunosuppressants have not been well assessed in this setting, but methotrexate has been better evaluated than the others. PMID:20027717

  7. Integrating anti-EGFR therapies in metastatic colorectal cancer

    PubMed Central

    Haraldsdottir, Sigurdis

    2013-01-01

    Colorectal cancer remains one of the most common causes of cancer diagnoses and mortality in the United States. The treatment of metastatic colorectal cancer has evolved significantly over the last decade with near-tripling of patient survival rate. A significant contribution to this outcome was the advent of novel targeted agents, such as the epidermal growth factor (EGFR) inhibitors. In an era of emphasis on refining therapy, the presence of KRAS mutation will predict for resistance and limit exposure to patients who are more likely to benefit. In contrast, the presence of BRAF mutations does not seem to have a predictive value. Agents that are thought to reverse resistance to EGFR inhibitors such as those targeting PI3K, c-MET or IGF-1R are currently under study. EGFR inhibitors have exhibited single agent activity, and seem to synergize very well with standard chemotherapy except for cetuximab and 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX). Preliminary data suggests that EGFR inhibitors have similar effectiveness to vascular endothelial growth factor (VEGF) inhibitors in the first line setting. Skin toxicity remains the main limiting factor for the utilization of EGFR inhibitors, but strategies including the use of agents such as minocycline or doxycycline added to topical care seem to limit the severity of the rash. PMID:23997940

  8. Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma.

    PubMed

    Hugo, Willy; Zaretsky, Jesse M; Sun, Lu; Song, Chunying; Moreno, Blanca Homet; Hu-Lieskovan, Siwen; Berent-Maoz, Beata; Pang, Jia; Chmielowski, Bartosz; Cherry, Grace; Seja, Elizabeth; Lomeli, Shirley; Kong, Xiangju; Kelley, Mark C; Sosman, Jeffrey A; Johnson, Douglas B; Ribas, Antoni; Lo, Roger S

    2016-03-24

    PD-1 immune checkpoint blockade provides significant clinical benefits for melanoma patients. We analyzed the somatic mutanomes and transcriptomes of pretreatment melanoma biopsies to identify factors that may influence innate sensitivity or resistance to anti-PD-1 therapy. We find that overall high mutational loads associate with improved survival, and tumors from responding patients are enriched for mutations in the DNA repair gene BRCA2. Innately resistant tumors display a transcriptional signature (referred to as the IPRES, or innate anti-PD-1 resistance), indicating concurrent up-expression of genes involved in the regulation of mesenchymal transition, cell adhesion, extracellular matrix remodeling, angiogenesis, and wound healing. Notably, mitogen-activated protein kinase (MAPK)-targeted therapy (MAPK inhibitor) induces similar signatures in melanoma, suggesting that a non-genomic form of MAPK inhibitor resistance mediates cross-resistance to anti-PD-1 therapy. Validation of the IPRES in other independent tumor cohorts defines a transcriptomic subset across distinct types of advanced cancer. These findings suggest that attenuating the biological processes that underlie IPRES may improve anti-PD-1 response in melanoma and other cancer types. PMID:26997480

  9. Efficacy and safety of anti-epidermal growth factor receptor therapy compared with anti-vascular endothelial growth factor therapy for metastatic colorectal cancer in first-line and second-line therapies: a meta-analysis

    PubMed Central

    Wang, Hongchi; Ma, Bin; Gao, Peng; Song, Yongxi; Xu, Qingzhou; Hu, Yaoyuan; Zhang, Cong; Wang, Zhenning

    2016-01-01

    Aim This study aimed to compare anti-epidermal growth factor receptor (anti-EGFR) therapy and anti-vascular endothelial growth factor therapy as first-line and second-line therapies in patients with KRAS exon 2 codon 12/13 wild-type (KRAS-WT) metastatic colorectal cancer (mCRC). Methods Major databases were systematically searched. The hazard ratio (HR), odds ratio (OR), and 95% confidence intervals (95% CIs) were used to estimate the effect measures. Review Manager software version 5.3 was used for statistical analysis. Results Seven trials including ten articles were eligible in the meta-analysis. The patients treated with anti-EGFR as first-line therapy showed a longer overall survival (OS) for KRAS-WT and all RAS wild-type (RAS-WT) mCRC (HR =0.81, 95% CI: 0.72–0.92, P<0.01, n=5; HR =0.78, 95% CI: 0.66–0.93, P<0.01, n=3, respectively). The objective response rate (ORR) was better with the anti-EGFR therapy for KRAS-WT and all RAS-WT mCRC (OR =1.32, 95% CI: 1.11–1.56, P<0.01, n=5; OR =1.55, 95% CI: 1.21–2.00, P<0.01, n=3, respectively). There was no difference in progression-free survival (PFS) for KRAS-WT mCRC and all RAS-WT mCRC between the two groups (HR =1.00; 95% CI: 0.92–1.09, P=0.99, n=4; HR =0.92, 95% CI: 0.71–1.19, P=0.52, n=3, respectively). In addition, two trials provided data on the second-line therapy; there was no significant difference in OS and PFS for the second-line therapy, but a significant improvement in ORR was found in the anti-EGFR group (OR =1.91, 95% CI: 1.16–3.16, P=0.01, n=2). No difference in the conversion therapy (OR =1.34; 95% CI: 0.91–1.99; P=0.14, n=4) was observed between the two therapies. Conclusion Our results indicate that anti-EGFR therapy is superior to anti-vascular endothelial growth factor therapy for OS and ORR as a first-line therapy for KRAS-WT mCRC. In the second-line therapy, there was no significant difference in the survival outcomes on the basis of OS and PFS between the two groups. However, ORR

  10. [Vascular and renal effects of anti-angiogenic therapy].

    PubMed

    Halimi, Jean-Michel; Azizi, Michel; Bobrie, Guillaume; Bouché, Olivier; Deray, Gilbert; des Guetz, Gaetan; Lecomte, Thierry; Levy, Bernard; Mourad, Jean-Jacques; Nochy, Dominique; Oudard, Stéphane; Rieu, Philippe; Sahali, Dil

    2008-12-01

    Angiogenesis inhibitor drugs (bevacizumab, sunitinib, sorafénib...) are now widely used for treatment of cancers, including colorectal, advanced renal cell and hepatocellular carcinomas, breast cancer). Vascular and renal side-effects of these drugs are not well known. Hypertension is one of the most common side effects. Incidence of hypertension may be different among angiogenis inhibitors and seems dose-depend. Arterial pressure can usually be controlled with anti-hypertensive medications, and treatment with angiogenesis inhibitors can be continued in most cases; however, serious hypertension-induced side effects were reported included malignant hypertension, stroke and reversible posterior leucoencephalopathy. Renal damage is infrequently reported: usually reversible mild or moderate proteinuria and in some rare cases nephritic syndrome, acute renal dysfunction, proliferative or collapsing glomerulonephritis, interstitial nephritis and thrombotic microangiopathy. Prolongation of the QT interval, congestive heart failure and left ventricular dysfunction have been reported in patients using tinibs. In the present guidelines, we recommend: (1) before the first administration of angiogenesis inhibitors: acute IV or oral antihypertensive medications should not be administered in a patient regardless of arterial pressure levels with postponing the administration because of hypertension is not recommended; (2) initial work-up should include ambulatory measurement of arterial pressure (by the general practitioner or by the patient using home blood pressure (three times in the morning and in the evening during three consecutive days) with a validated (cf: http://afssaps.sante.fr/) upper arm device: ideally, this device should be financed and provided by the pharmaceutical companies marketing the angiogenesis inhibitor drugs. Using 24-hour ambulatory blood pressure measurement is optional; (3) urine dipstick (and quantification if positive) and estimated glomerular

  11. Soluble Tie2 overrides the heightened invasion induced by anti-angiogenesis therapies in gliomas.

    PubMed

    Cortes-Santiago, Nahir; Hossain, Mohammad B; Gabrusiewicz, Konrad; Fan, Xuejun; Gumin, Joy; Marini, Frank C; Alonso, Marta M; Lang, Frederick; Yung, W K; Fueyo, Juan; Gomez-Manzano, Candelaria

    2016-03-29

    Glioblastoma recurrence after treatment with the anti-vascular endothelial growth factor (VEGF) agent bevacizumab is characterized by a highly infiltrative and malignant behavior that renders surgical excision and chemotherapy ineffective. Our group has previously reported that Tie2-expressing monocytes (TEMs) are aberrantly present at the tumor/normal brain interface after anti-VEGF therapies and their significant role in the invasive outgrowth of these tumors. Here, we aimed to further understand the mechanisms leading to this pro-invasive tumor microenvironment. Examination of a U87MG xenogeneic glioma model and a GL261 murine syngeneic model showed increased tumor expression of angiopoietin 2 (Ang2), a natural ligand of Tie2, after anti-angiogenesis therapies targeting VEGF or VEGF receptor (VEGFR), as assessed by immunohistochemical analysis, immunofluorescence analysis, and enzyme-linked immunosorbent assays of tumor lysates. Migration and gelatinolytic assays showed that Ang2 acts as both a chemoattractant of TEMs and an enhancing signal for their tumor-remodeling properties. Accordingly, in vivo transduction of Ang2 into intracranial gliomas increased recruitment of TEMs into the tumor. To reduce invasive tumor outgrowth after anti-angiogenesis therapy, we targeted the Ang-Tie2 axis using a Tie2 decoy receptor. Using syngeneic models, we observed that overexpression of soluble Tie2 within the tumor prevented the recruitment of TEMs to the tumor and the development of invasion after anti-angiogenesis treatment. Taken together, these data indicate an active role for the Ang2-Tie2 pathway in invasive glioma recurrence after anti-angiogenesis treatment and provide a rationale for testing the combined targeting of VEGF and Ang-Tie2 pathways in patients with glioblastoma. PMID:26910374

  12. Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future.

    PubMed

    Chen, Lieping; Han, Xue

    2015-09-01

    Major progress has been made toward our understanding of the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) pathway (referred to as the PD pathway). mAbs are already being used to block the PD pathway to treat human cancers (anti-PD therapy), especially advanced solid tumors. This therapy is based on principles that were discovered through basic research more than a decade ago, but the great potential of this pathway to treat a broad spectrum of advanced human cancers is just now becoming apparent. In this Review, we will briefly review the history and development of anti-PD therapy, from the original benchwork to the most up-to-date clinical results. We will then focus the discussion on three basic principles that define this unique therapeutic approach and highlight how anti-PD therapy is distinct from other immunotherapeutic approaches, namely tumor site immune modulation, targeting tumor-induced immune defects, and repairing ongoing (rather than generating de novo) tumor immunity. We believe that these fundamental principles set the standard for future immunotherapies and will guide our efforts to develop more efficacious and less toxic immune therapeutics to treat human cancers. PMID:26325035

  13. The Role of Anti-VEGF Therapy in the Treatment of Diabetic Macular Edema.

    PubMed

    Moshfeghi, Darius M; Kaiser, Peter K; Michels, Stephan; Midena, Edoardo; Kitchens, John W; Prenner, Jonathan L; Regillo, Carl D; Reichel, Elias

    2016-06-01

    Diabetic retinopathy (DR) is the leading cause of blindness among working-age adults. DR often leads to diabetic macular edema (DME), which often goes unnoticed until a patient presents with vision loss. However, treatment options and data for DME are continually improving. We know that vascular endothelial growth factor (VEGF) plays a key role in DME progression; therapies that act by inhibiting VEGF production seem to improve visual acuity in patients with DME. Of the anti-VEGF therapies available, two have been approved by the U.S. Food and Drug Administration to treat DME: ranibizumab (Lucentis; Genentech, South San Francisco, CA) and aflibercept (Eylea; Regeneron, Tarrytown, NY). Bevacizumab (Avastin; Genentech, South San Francisco, CA), which is approved for the treatment of certain types of cancer, is occasionally used off-label to treat DME. Anti-VEGF therapy can stop vision loss and even improve visual acuity. Other treatments remain effective, and these various treatment options fuel a need for new data and discussion. This roundtable discussion, which took place during the 2015 annual meeting of the American Academy of Ophthalmology, outlines the current protocols used to treat DME and provides clinical opinions about selecting and treating with an appropriate anti-VEGF therapy. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:S5-14.]. PMID:27348433

  14. Dynamics of tumor growth and combination of anti-angiogenic and cytotoxic therapies

    NASA Astrophysics Data System (ADS)

    Kohandel, M.; Kardar, M.; Milosevic, M.; Sivaloganathan, S.

    2007-07-01

    Tumors cannot grow beyond a certain size (about 1-2 mm in diameter) through simple diffusion of oxygen and other essential nutrients into the tumor. Angiogenesis, the formation of blood vessels from pre-existing vessels, is a crucial and observed step, through which a tumor obtains its own blood supply. Thus, strategies that interfere with the development of this tumor vasculature, known as anti-angiogenic therapy, represent a novel approach to controlling tumor growth. Several pre-clinical studies have suggested that currently available angiogenesis inhibitors are unlikely to yield significant sustained improvements in tumor control on their own, but rather will need to be used in combination with conventional treatments to achieve maximal benefit. Optimal sequencing of anti-angiogenic treatment and radiotherapy or chemotherapy is essential to the success of these combined treatment strategies. Hence, a major challenge to mathematical modeling and computer simulations is to find appropriate dosages, schedules and sequencing of combination therapies to control or eliminate tumor growth. Here, we present a mathematical model that incorporates tumor cells and the vascular network, as well as their interplay. We can then include the effects of two different treatments, conventional cytotoxic therapy and anti-angiogenic therapy. The results are compared with available experimental and clinical data.

  15. Lichenoid dermatitis in three patients with metastatic melanoma treated with anti-PD-1 therapy.

    PubMed

    Joseph, Richard W; Cappel, Mark; Goedjen, Brent; Gordon, Matthew; Kirsch, Brandon; Gilstrap, Cheryl; Bagaria, Sanjay; Jambusaria-Pahlajani, Anokhi

    2015-01-01

    Therapies that activate the immune system through blocking the binding of programmed death ligand 1 (PD-L1) present on tumors and PD-1 (programmed death 1) present on activated immune cells are revolutionizing the care for patients with cancer. These therapies work by inhibiting negative regulators of the immune system, thereby decreasing a tumor's ability to evade the immune system. The side effects of anti-PD-1/PD-L1 therapies are generally mild and as expected are related to autoimmune reactions. Two of the most common side effects of anti-PD-1/PD-L1 therapies are rash and pruritus occurring in approximately 20% of patients. Although the rash is generally recognized to be immune mediated, the exact mechanisms of the rash remain unclear. Herein, we report three cases of lichenoid dermatitis in three patients treated with MK-3475 (anti-PD-1) that were characterized with marked T-cell infiltrates with few PD-1-positive cells. The rashes in all three patients were relatively mild, allowing treatment to continue despite the rashes. PMID:25287118

  16. Pharmacogenetics and anti-arrhythmic drug therapy: a theoretical investigation

    PubMed Central

    Clancy, Colleen E.; Zhu, Zheng I.; Rudy, Yoram

    2007-01-01

    Pharmacological management of cardiac arrhythmias has been a long and widely sought goal. One of the difficulties in treating arrhythmia stems, in part, from incomplete understanding of the mechanisms of drug block and how intrinsic properties of channel gating affect drug access, binding affinity, and unblock. In the last decade, a plethora of genetic information has revealed that genetics may play a critical role in determining arrhythmia susceptibility and in efficacy of pharmacological therapy. In this context, we present a theoretical approach for investigating effects of drug-channel interaction. We use as an example open-channel or inactivated-channel block by the local anesthetics mexiletine and lidocaine, respectively, of normal and ΔKPQ mutant Na+ channels associated with the long-QT syndrome type 3. Results show how kinetic properties of channel gating, which are affected by mutations, are important determinants of drug efficacy. Investigations of Na+ channel blockade are conducted at multiple scales (single channel and macroscopic current) and, importantly, during the cardiac action potential (AP). Our findings suggest that channel mean open time is a primary determinant of open state blocker efficacy. Channels that remain in the open state longer, such as the ΔKPQ mutant channels in the abnormal burst mode, are blocked preferentially by low mexiletine concentrations. AP simulations confirm that a low dose of mexiletine can remove early afterdepolarizations and restore normal repolarization without affecting the AP upstroke. The simulations also suggest that inactivation state block by lidocaine is less effective in restoring normal repolarization and adversely suppresses peak Na+ current. PMID:16997895

  17. Psoriasis and psoriatic arthritis overview.

    PubMed

    Menter, Alan

    2016-06-01

    Psoriasis and psoriatic arthritis (PsA) are chronic immune-mediated diseases that primarily affect the skin and joints, respectively; these diseases are also associated with high rates of cardiovascular and other comorbidities. Despite over 40 genes proven to be related to the disease, the exact causes of psoriasis and PsA are still to be determined. Recent insights into the underlying pathophysiology of these diseases have revealed novel therapeutic targets. Effective management requires timely diagnosis and initiation of treatment. Yet, both psoriasis and PsA remain underrecognized and undertreated in current clinical practice. Recognizing the true physical, social, and emotional burden of psoriasis and PsA, as well as their associated comorbidities, is the first step to improving the prognosis for affected patients. PMID:27356193

  18. A scientific approach to anti-ageing therapies: state of the art.

    PubMed

    Jirillo, E; Candore, G; Magrone, T; Caruso, C

    2008-01-01

    A lasting dream of human beings is to reverse or at least postpone ageing. During the last years, an increasing number of scientific meetings, articles, and books have been devoted to anti-ageing therapies. This subject, full of misleading, simplistic, or wrong ideas, is very popular among the general public, whose imagery has been fascinated by all possible tools to delay ageing, getting immortality. Here, we discuss anti-ageing strategies aimed not to rejuvenate but to slow ageing and delay the onset of age-related diseases. These approaches should be able to substantially slow down the ageing process, extending our productive, youthful lives. PMID:18991682

  19. Why so little effort to study anti-oxidant therapy in burns?

    PubMed

    Klein, Gordon L

    2016-01-01

    Given that oxidative stress is an inherent response to burn injury, it is puzzling as to why investigation into anti-oxidant therapy as an adjunct to burn treatment has been limited. Both the inflammatory response and the stress response to burn injury involve oxidative stress, and there has been some limited success in studies using gamma tocopherol and selenium to improve certain consequences of burns. Much remains to be done to investigate the number, doses and combinations of anti-oxidants, their efficacy, and limitations in improving defined outcomes after burn injury. PMID:27574696

  20. Anti dermatophytic therapy - Prospects for the discovery of new drugs from natural products

    PubMed Central

    Soares, Luciana Arantes; de Cássia Orlandi Sardi, Janaína; Gullo, Fernanda Patrícia; de Souza Pitangui, Nayla; Scorzoni, Liliana; Leite, Fernanda Sangalli; Giannini, Maria José Soares Mendes; Almeida, Ana Marisa Fusco

    2013-01-01

    Millions of people and animals suffer from superficial infections caused by a group of highly specialized filamentous fungi, the dermatophytes, which only infect keratinized structures. With the appearance of AIDS, the incidence of dermatophytosis has increased. Current drug therapy used for these infections is often toxic, long-term, and expensive and has limited effectiveness; therefore, the discovery of new anti dermatophytic compounds is a necessity. Natural products have been the most productive source for new drug development. This paper provides a brief review of the current literature regarding the presence of dermatophytes in immunocompromised patients, drug resistance to conventional treatments and new anti dermatophytic treatments. PMID:24688490

  1. IL-36γ (IL-1F9) is a biomarker for psoriasis skin lesions.

    PubMed

    D'Erme, Angelo Massimiliano; Wilsmann-Theis, Dagmar; Wagenpfeil, Julia; Hölzel, Michael; Ferring-Schmitt, Sandra; Sternberg, Sonja; Wittmann, Miriam; Peters, Bettina; Bosio, Andreas; Bieber, Thomas; Wenzel, Joerg

    2015-04-01

    In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not only psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/tumor necrosis factor-α (TNFα)-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses, IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, because of its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation. PMID:25525775

  2. Drug exposure and psoriasis vulgaris: case-control and case-crossover studies.

    PubMed

    Cohen, Arnon D; Bonneh, Dan Y; Reuveni, Haim; Vardy, Daniel A; Naggan, Lechaim; Halevy, Sima

    2005-01-01

    Intake of drugs is considered a risk factor for psoriasis. The aim of this study was to investigate the association between drugs and psoriasis. A case-control study including 110 patients who were hospitalized for extensive psoriasis was performed. A control group (n = 515) was defined as patients who had undergone elective surgery. A case-crossover study included 98 patients with psoriasis. Exposure to drugs was assessed during a hazard period (3 months before hospitalization) and compared to a control period in the patient's past. Data on drug sales were extracted by data mining techniques. Multivariate analyses were performed by logistic regression and conditional logistic regression. In the case-control study, psoriasis was associated with benzodiazepines (OR 6.9), organic nitrates (OR 5.0), angiotensin-converting enzyme (ACE) inhibitors (OR 4.0) and non-steroidal anti-inflammatory drugs (NSAIDs) (OR 3.7). In the case-crossover study, psoriasis was associated with ACE inhibitors (OR 9.9), beta-blockers (OR 9.9), dipyrone (OR 4.9) and NSAIDs (OR 2.1). Extensive psoriasis may be associated with intake of ACE inhibitors, NSAIDs or beta-blockers. PMID:16191849

  3. TUR-PSO: A cross-sectional, study investigating quality of life and treatment status of psoriasis patients in Turkey.

    PubMed

    Atakan, Nilgün; Yazici, Ayça Cordan; Özarmağan, Güzin; İnalÖz, Hüseyin Serhat; Gürer, Mehmet Ali; Sabuncu, İlham; Kİremİtçİ, Ümmühan; Alper, Sibel; Aytekİn, Sema; Arican, Özer; Polat, Mualla; Doğan, Sibel; Aldİnç, Emre

    2016-03-01

    Psoriasis is a common inflammatory disease that has a severe impact on quality of life. There is lack of data regarding epidemiological and clinical features of psoriasis patients in Turkey, a country with a population of 76 million. The aim of this study was to define the demographic and clinical characteristics, quality of life and treatment patterns of psoriasis patients in Turkey. A cross-sectional observational study was conducted at 40 centers, chosen from geographically diverse locations in Turkey. Patients diagnosed with psoriasis were assessed by investigators who were specialists of dermatology using standardized study questionnaire forms. Dermatology Life Quality Index (DLQI) and EuroQol-5 dimension (EQ-5D) forms were also filled out by each patient. 3971 psoriasis patients were included in this study. 24.2% of plaque psoriasis patients had moderate to severe psoriasis (Psoriasis Area and Severity Index, ≥10). Mean DLQI was 7.03 ± 6.02; quality of life was moderately, severely or very severely affected in 49.2% of patients. The most severely affected component of EQ-5D was anxiety/depression. Among all patients, 22.9% were not receiving any treatment, 39.8% were receiving only topical treatment, 11.5% were on phototherapy, 26.1%, were taking conventional systemic agents and 4.1% were on a biologic treatment. 31.3% of psoriasis patients with moderate to severe disease were treated with only topical agents and only 30.5% of moderate to severe psoriasis patients were receiving systemic therapy. Moderate to severe psoriasis has a considerable impact on quality of life. Treatment in Turkey of patients with moderate to severe psoriasis is insufficient. PMID:26365805

  4. Psoriasis in Children: A Review.

    PubMed

    Balato, Anna; Scalvenzi, Massimiliano; Cirillo, Teresa; Gallo, Lucia; Ayala, Fabio; Balato, Nicola

    2015-01-01

    Psoriasis is a chronic, immune-mediated, inflammatory systemic disease which targets primarily the skin. It presents a genetic basis, affecting 1 to 3% of the white population. Nevertheless, the existence of two psoriasis incidence peaks has been suggested (one in adolescence before 20 years of age and another in adulthood) onset may occur at any age, including childhood and adolescence, in which its prevalence ranges between 0.7% and 1.2%. As for adult psoriasis, pediatric psoriasis has recently been associated with obesity, metabolic syndrome, increased waist circumference percentiles, and metabolic laboratory abnormalities, warranting early monitoring and lifestyle modifications. In addition, due to psoriasis chronic nature and frequently occurring relapses, psoriatic patients tend to have an impaired quality of life, often requiring long-term treatment. Therefore, education of both pediatric patients and their parents is essential to successful and safe disease management. However, systemic treatment of children is challenging as the absence of standardized guidelines and the fact that evidence-based data form randomized controlled trials are very limited. This review shows an overview of the current understanding of the pathogenesis, comorbidities, differential diagnosis, treatment and prevention of pediatric psoriasis, also presenting with an emphasis on the necessity of an integrated treatment approach involving different specialists such as dermatologist, pediatricians, rheumatologists, etc. PMID:25938378

  5. Urinary Biopyrrins: A New Marker of Oxidative Stress in Psoriasis

    PubMed Central

    Bakry, Ola Ahmed; El Hefnawy, Sally; Mariee, Alaa Hassan; El Gendy, Yara

    2016-01-01

    Background: Psoriasis is a common chronic, relapsing, immune-mediated disease involving skin and joints of genetically predisposed individuals. Oxidative stress has been found to play many important roles in cellular damage and loss of function in a number of tissues and organs and is believed to contribute to the pathogenesis of a variety of diseases. Urinary biopyrrin levels have gained attention as an indicator of oxidative stress. Aim and Objective: To measure urinary biopyrrins excretion as a marker of oxidative stress in psoriasis. Patients and Methods: This case–control study was carried out on 85 subjects; 55 cases with chronic plaque psoriasis and 30 age, gender and body mass index-matched normal subjects as a control group. Urinary biopyrrin levels were measured using enzyme immunoassay. Results: There was a highly significant difference between cases and controls regarding urinary biopyrrins level (P < 0.001). There was significant positive correlation between biopyrrins level and both the age of cases (r = 0.28, P = 0.01) and psoriasis area and severity index score (r = 0.99, P < 0.001). Conclusion: Urinary biopyrrins are increased in patients with psoriasis, and the level is correlated with disease severity. Further large-scale studies involving different ages and different clinical varieties of the disease are needed to expand and validate current findings. The clinical usefulness of antioxidants in psoriasis treatment needs to be evaluated in future research. Furthermore, the value of biopyrrins as biomarkers for monitoring response to therapy needs to be evaluated. PMID:27057016

  6. Barriers to guideline-compliant psoriasis care: analyses and concepts.

    PubMed

    Eissing, L; Radtke, M A; Zander, N; Augustin, M

    2016-04-01

    Despite the availability of effective therapeutics and evidence-based treatment guidelines, a substantial proportion of patients with moderate-to-severe psoriasis does not receive appropriate care. This under-provision of health care may cause further worsening of health, remarkable limitations of the patient's quality of life, and indirect costs for the health care system. In order to provide guideline-compliant care for every psoriasis patient, it is important to identify barriers obstructing optimal care. Studies have identified various barriers on the physician's and on the patient's side; however, respective studies approached only single barriers, and not all of them in the context of psoriasis. Other publications that describe barriers systematically did not focus on psoriasis either. The objective of this literature review was to identify barriers and facilitators, based on studies analysing quality of care and single barriers, resulting in a comprehensive model of causal factors. Our analyses revealed three categories of barriers - patient-related, physician-related and external factors: On the patient side, we found non-adherence to therapies to be an important barrier, often in close association with psychiatric factors. Barriers on the physician's side predominantly are incomplete knowledge of the guidelines as well as the complexity of psoriasis comorbidity. In some countries, payment for patients with complex disease status is poor and inconsistent reimbursement regulations potentially interfere with optimal care. The current analysis indicates that most barriers are interdependent. Thus, measures approaching related barriers simultaneously are required. To improve care for psoriasis patients, further studies systematically addressing all potentially relevant barriers in conjoint are needed. PMID:26538533

  7. Anti-psoriatic treatment extends beyond the skin: Recovering of high-density lipoprotein function

    PubMed Central

    Marsche, Gunther; Holzer, Michael; Wolf, Peter

    2016-01-01

    Epidemiological and clinical studies have shown a consistent association of psoriasis with systemic metabolic disorders including an increased prevalence of diabetes, obesity and cardiovascular disease. Psoriasis is accompanied by systemic inflammation and low levels of high-density lipoprotein (HDL)-cholesterol. Recent studies provided clear evidence that psoriasis affects HDL composition and function. HDL isolated from psoriatic patients showed a significantly impaired capability to mobilize cholesterol from macrophages, a crucial step in reverse cholesterol transport and markedly lower paraoxonase activity, a protein that co-transports with HDL in serum with well-known anti-atherogenic properties. Of particular interest, successful anti-psoriatic therapy significantly improved HDL composition and function independently of serum HDL-cholesterol levels. These novel findings suggest that the conventional approaches of evaluating cardiovascular risk in psoriasis may be in need of refinement. As these data argue for a loss of beneficial activities of HDL in psoriatic patients, altered HDL functionality should be considered when evaluating the lipid status of patients. PMID:24980461

  8. New onset psoriasis in a patient receiving abatacept for rheumatoid arthritis

    PubMed Central

    Jost, Christina; Hermann, Josef; Caelen, Laila El-Shabrawi; Graninger, Winfried

    2009-01-01

    Administration of abatacept is a new treatment modality for rheumatoid arthritis (RA). We describe a patient in whom psoriasiform skin lesions developed 4 months after the initiation of abatacept therapy for longstanding, rheumatoid factor positive RA. Histological findings were consistent with psoriasis. The skin lesions subsided after discontinuation of abatacept and reappeared after re-exposure to the drug, suggesting a causal connection between abatacept and the development of psoriasis. PMID:21686603

  9. Supersonic Shear Wave Elastography of Response to Anti-cancer Therapy in a Xenograft Tumor Model.

    PubMed

    Chamming's, Foucauld; Le-Frère-Belda, Marie-Aude; Latorre-Ossa, Heldmuth; Fitoussi, Victor; Redheuil, Alban; Assayag, Franck; Pidial, Laetitia; Gennisson, Jean-Luc; Tanter, Mickael; Cuénod, Charles-André; Fournier, Laure S

    2016-04-01

    Our objective was to determine if supersonic shear wave elastography (SSWE) can detect changes in stiffness of a breast cancer model under therapy. A human invasive carcinoma was implanted in 22 mice. Eleven were treated with an anti-angiogenic therapy and 11 with glucose for 24 d. Tumor volume and stiffness were assessed during 2 wk before treatment and 0, 7, 12, 20 and 24 d after the start of therapy using SSWE. Pathology was assessed after 12 and 24 d of treatment. We found that response to therapy was associated with early softening of treated tumors only, resulting in a significant difference from non-treated tumors after 12 d of treatment (p = 0.03). On pathology, large areas of necrosis were observed at 12 d in treated tumors. Although treatment was still effective, treated tumors subsequently stiffened during a second phase of the treatment (days 12-24), with a small amount of necrosis observed on pathology on day 24. In conclusion, SSWE was able to measure changes in the stiffness of tumors in response to anti-cancer treatment. However, stiffness changes associated with good response to treatment may change over time, and increased stiffness may also reflect therapy efficacy. PMID:26746382

  10. Clinical and economic review of secukinumab for moderate-to-severe plaque psoriasis.

    PubMed

    Wong, Ian Ty; Shojania, Kam; Dutz, Jan; Tsao, Nicole W

    2016-01-01

    Secukinumab represents the first IL-17A antagonist among the available biologic therapies approved for moderate-to-severe plaque psoriasis management. Secukinumab demonstrated greater efficacy over placebo, etanercept and ustekinumab in patients that had limited benefit from non-biologic systemic therapies and phototherapy. Despite standard-of-care systemic therapies being more likely to be cost-effective at this time, a Canadian cost-utility analysis found secukinumab to display benefit in quality-of-life gains in moderate-to-severe plaque psoriasis patients, and greater cost-effectiveness when compared to other biologic systemic therapies. Determination of the true economic value of secukinumab amongst the available therapies for moderate-to-severe plaque psoriasis will require continued economic evaluation. PMID:26681527

  11. Mediastinal sarcoidosis mimicking lymph malignancy recurrence after anti-neoplastic therapy.

    PubMed

    El Hammoumi, Massine; El Marjany, Mohamed; Moussaoui, Driss; Doudouh, Aberahim; Mansouri, Hamid; Kabiri, El Hassane

    2015-07-01

    The aim of our work is to promote the awareness about the development of sarcoidosis after antineoplastic therapy in order to avoid diagnostic errors with FDG-PET/CT findings. We report the observation of three women with breast, cervix and stomach treated cancers who developed a sarcoidosis after the end of anti-neoplastic therapy. The utility of FDG-PET/CT is in pinpointing the organs candidates for diagnostic biopsy and not distinguishing between the malignancy and granulomatous or inflammatory diseases. PMID:25294405

  12. [A short history of anti-rheumatic therapy. I. An introduction on traditional and drug treatments].

    PubMed

    Pasero, G; Marson, P

    2010-01-01

    The origins of anti-rheumatic therapy are very old and mainly related to the use of traditional, sometimes extravagant, treatments, as a part of folk medicine. Spa therapy has long been used for the treatment of rheumatic diseases, as well as, in later times, physical treatments, including electrotherapy. Drug treatment has developed beginning from substances of vegetable origin, such as willow and colchicum extracts. Then it has been spread out through the chemical synthesis of compounds with specific action and therefore more effective, owing to the great development of pharmaceutical industry. PMID:20390121

  13. The dual role of complement in cancer and its implication in anti-tumor therapy

    PubMed Central

    2016-01-01

    Chronic inflammation has been linked to the initiation of carcinogenesis, as well as the advancement of established tumors. The polarization of the tumor inflammatory microenvironment can contribute to either the control, or the progression of the disease. The emerging participation of members of the complement cascade in several hallmarks of cancer, renders it a potential target for anti-tumor treatment. Moreover, the presence of complement regulatory proteins (CRPs) in most types of tumor cells is known to impede anti-tumor therapies. This review focuses on our current knowledge of complement’s potential involvement in shaping the inflammatory tumor microenvironment and its role on the regulation of angiogenesis and hypoxia. Furthermore, we discuss approaches using complement-based therapies as an adjuvant in tumor immunotherapy. PMID:27563652

  14. Metabolic reprogramming induces resistance to anti-NOTCH1 therapies in acute lymphoblastic leukemia

    PubMed Central

    Herranz, Daniel; Ambesi-Impiombato, Alberto; Sudderth, Jessica; Sánchez-Martín, Marta; Belver, Laura; Tosello, Valeria; Xu, Luyao; Wendorff, Agnieszka A.; Castillo, Mireia; Haydu, J. Erika; Márquez, Javier; Matés, José M.; Kung, Andrew L.; Rayport, Stephen; Cordon-Cardo, Carlos; DeBerardinis, Ralph J.; Ferrando, Adolfo A.

    2015-01-01

    Activating mutations in NOTCH1 are common in T-cell acute lymphoblastic leukemia (TALL). Here we identify glutaminolysis as a critical pathway for leukemia cell growth downstream of NOTCH1 and a key determinant of clinical response to anti-NOTCH1 therapies. Mechanistically, inhibition of NOTCH1 signaling in T-ALL induces a metabolic shutdown with prominent inhibition of glutaminolysis and triggers autophagy as a salvage pathway supporting leukemia cell metabolism. Consequently, both inhibition of glutaminolysis and inhibition of autophagy strongly and synergistically enhance the antileukemic effects of anti-NOTCH1 therapies. Moreover, we demonstrate that Pten loss induces increased glycolysis and consequently rescues leukemic cell metabolism abrogating the antileukemic effects of NOTCH1 inhibition. Overall, these results identify glutaminolysis as a major node in cancer metabolism controlled by NOTCH1 and as therapeutic target for the treatment of T-ALL. PMID:26390244

  15. Soluble Tie2 overrides the heightened invasion induced by anti-angiogenesis therapies in gliomas

    PubMed Central

    Cortes-Santiago, Nahir; Hossain, Mohammad B.; Gabrusiewicz, Konrad; Fan, Xuejun; Gumin, Joy; Marini, Frank C.; Alonso, Marta M.; Lang, Frederick; Yung, W.K.; Fueyo, Juan; Gomez-Manzano, Candelaria

    2016-01-01

    Glioblastoma recurrence after treatment with the anti–vascular endothelial growth factor (VEGF) agent bevacizumab is characterized by a highly infiltrative and malignant behavior that renders surgical excision and chemotherapy ineffective. Our group has previously reported that Tie2-expressing monocytes (TEMs) are aberrantly present at the tumor/normal brain interface after anti-VEGF therapies and their significant role in the invasive outgrowth of these tumors. Here, we aimed to further understand the mechanisms leading to this pro-invasive tumor microenvironment. Examination of a U87MG xenogeneic glioma model and a GL261 murine syngeneic model showed increased tumor expression of angiopoietin 2 (Ang2), a natural ligand of Tie2, after anti-angiogenesis therapies targeting VEGF or VEGF receptor (VEGFR), as assessed by immunohistochemical analysis, immunofluorescence analysis, and enzyme-linked immunosorbent assays of tumor lysates. Migration and gelatinolytic assays showed that Ang2 acts as both a chemoattractant of TEMs and an enhancing signal for their tumor-remodeling properties. Accordingly, in vivo transduction of Ang2 into intracranial gliomas increased recruitment of TEMs into the tumor. To reduce invasive tumor outgrowth after anti-angiogenesis therapy, we targeted the Ang-Tie2 axis using a Tie2 decoy receptor. Using syngeneic models, we observed that overexpression of soluble Tie2 within the tumor prevented the recruitment of TEMs to the tumor and the development of invasion after anti-angiogenesis treatment. Taken together, these data indicate an active role for the Ang2-Tie2 pathway in invasive glioma recurrence after anti-angiogenesis treatment and provide a rationale for testing the combined targeting of VEGF and Ang-Tie2 pathways in patients with glioblastoma. PMID:26910374

  16. Moving Past Anti-VEGF: Novel Therapies for Treating Diabetic Retinopathy.

    PubMed

    Bolinger, Mark T; Antonetti, David A

    2016-01-01

    Diabetic retinopathy is the leading cause of blindness in working age adults, and is projected to be a significant future health concern due to the rising incidence of diabetes. The recent advent of anti-vascular endothelial growth factor (VEGF) antibodies has revolutionized the treatment of diabetic retinopathy but a significant subset of patients fail to respond to treatment. Accumulating evidence indicates that inflammatory cytokines and chemokines other than VEGF may contribute to the disease process. The current review examines the presence of non-VEGF cytokines in the eyes of patients with diabetic retinopathy and highlights mechanistic pathways in relevant animal models. Finally, novel drug targets including components of the kinin-kallikrein system and emerging treatments such as anti-HPTP (human protein tyrosine phosphatase) β antibodies are discussed. Recognition of non-VEGF contributions to disease pathogenesis may lead to novel therapeutics to enhance existing treatments for patients who do not respond to anti-VEGF therapies. PMID:27618014

  17. [Topical treatments for psoriasis in 2009].

    PubMed

    Thielen, Anne-Marie; Laffitte, Emmanuel

    2009-04-22

    Psoriasis is a chronic inflammatory disease causing important physical and psychological morbidity. Topical treatments are the first choice therapeutic alternatives for mild and moderate psoriasis. We review the different topical treatment options for this common skin disease. PMID:19438087

  18. Psoriasis Tied to Obesity, Type 2 Diabetes

    MedlinePlus

    ... gov/news/fullstory_158526.html Psoriasis Tied to Obesity, Type 2 Diabetes A genetic link is one ... prove that psoriasis causes type 2 diabetes or obesity or vice versa, Lonnberg added. However, the study ...

  19. Psoriasis: experiencing a chronic skin disease.

    PubMed

    Chrissopoulos, A; Cleaver, G

    1996-03-01

    Psoriasis is an incurable chronic skin disease that affects one in fifty people. Psychological factors play a role in the aetiology and experience of psoriasis but there is little pertaining to the psychological experience of psoriasis in research literature. In this study the phenomenological approach is used to describe the everyday experiences of a person with psoriasis. By using Giorgi's (1985) steps of data analysis a description of the lifeworld of the person with psoriasis was compiled. The description presented several essential components of the experience of psoriasis and the results emphasize the effects of the disease on the sufferer's life. Problematic interpersonal relationships, a negative selfconcept, fluctuating moods, loss of control, negativity and loneliness are a part of this experience. It is hoped that knowledge of the world of the psoriasis sufferer will assist the help professions to understanding and empathize with the suffering and limitations that psoriasis brings. PMID:9257576

  20. Psoriasis Tied to Obesity, Type 2 Diabetes

    MedlinePlus

    ... medlineplus/news/fullstory_158526.html Psoriasis Tied to Obesity, Type 2 Diabetes A genetic link is one ... prove that psoriasis causes type 2 diabetes or obesity or vice versa, Lonnberg added. However, the study ...

  1. Triggering drug use in patients with psoriasis: an investigative report from Turkey

    PubMed Central

    Ogretmen, Zerrin; Askin, Ulku; Cevizci, Sibel

    2014-01-01

    Introduction The patients clinically diagnosed with psoriasis were investigated for drug use that may trigger psoriasis. Aim To minimize the triggering drug use and help the medical treatment of psoriasis patients. Material and methods The study involved 289 psoriatic patients who attended our clinic in 2010–2012 and were asked to bring their drug lists of the last year, which they obtained from the pharmacy's record system. They were advised not to use the drugs that may trigger psoriasis. Data analyses were performed using SPSS program version 19.0. Results A total of 289 patients were included in the study. Two hundred and twenty-one patients were using non-steroidal anti-inflammatory drugs; 133 patients were using anti-reflux drugs; 35 patients were using antidiabetic drugs; 31 patients were using calcium-channel blockers and 24 patients were using β-blockers. In our study group, there was no significantly difference between median PASI scores of the patients using a triggering drug and those of who are not using a triggering drug. However, there was a positive low correlation between PASI rates and numbers of drugs used (r = 0.180, p = 0.013). Conclusions Many other factors may trigger psoriasis, therefore the effect of stopping or minimizing the drug use on disease remission is not known. Because of the high triggering drug use rate, it is important to enlighten psoriasis patients about triggering drugs. PMID:25395925

  2. A synonymous EGFR polymorphism predicting responsiveness to anti-EGFR therapy in metastatic colorectal cancer patients.

    PubMed

    Bonin, Serena; Donada, Marisa; Bussolati, Gianni; Nardon, Ermanno; Annaratone, Laura; Pichler, Martin; Chiaravalli, Anna Maria; Capella, Carlo; Hoefler, Gerald; Stanta, Giorgio

    2016-06-01

    Genetic factors are known to affect the efficiency of therapy with monoclonal antibodies (mAbs) targeting the epidermal growth factor receptor (EGFR) in patients with metastatic colorectal cancer (mCRC). At present, the only accepted molecular marker predictive of the response to anti-EGFR mAbs is the somatic mutation of KRAS and NRAS as a marker of resistance to anti-EGFR. However, only a fraction of KRAS wild-type patients benefit from that treatment. In this study, we show that the EGFR gene polymorphism rs1050171 defines, independently of RAS mutational status, a sub-population of 11 % of patients with a better clinical outcome after anti-EGFR treatment. Median PFS for patients with the GG genotype was 10.17 months compared to 5.37 of those with AG + AA genotypes. Taken together, our findings could be used to better define CRC populations responding to anti-EGFR therapy. Further studies in larger independent cohorts are necessary to validate the present observation that a synonymous polymorphism in EGFR gene impacts on clinical responsiveness. PMID:26666825

  3. The carboxyl terminus of VEGF-A is a potential target for anti-angiogenic therapy.

    PubMed

    Carter, James G; Gammons, Melissa V R; Damodaran, Gopinath; Churchill, Amanda J; Harper, Steven J; Bates, David O

    2015-01-01

    Anti-VEGF-A therapy has become a mainstay of treatment for ocular neovascularisation and in cancer; however, their effectiveness is not universal, in some cases only benefiting a minority of patients. Anti-VEGF-A therapies bind and block both pro-angiogenic VEGF-Axxx and the partial agonist VEGF-Axxxb isoforms, but their anti-angiogenic benefit only comes about from targeting the pro-angiogenic isoforms. Therefore, antibodies that exclusively target the pro-angiogenic isoforms may be more effective. To determine whether C-terminal-targeted antibodies could inhibit angiogenesis, we generated a polyclonal antibody to the last nine amino acids of VEGF-A165 and tested it in vitro and in vivo. The exon8a polyclonal antibody (Exon8apab) did not bind VEGF-A165b even at greater than 100-fold excess concentration, and dose dependently inhibited VEGF-A165 induced endothelial migration in vitro at concentrations similar to the VEGF-A antibody fragment ranibizumab. Exon8apab can inhibit tumour growth of LS174t cells implanted in vivo and blood vessel growth in the eye in models of age-related macular degeneration, with equal efficacy to non-selective anti-VEGF-A antibodies. It also showed that it was the VEGF-Axxx levels specifically that were upregulated in plasma from patients with proliferative diabetic retinopathy. These results suggest that VEGF-A165-specific antibodies can be therapeutically useful. PMID:25274272

  4. Anti-tumor effect of Radix Paeoniae Rubra extract on mice bladder tumors using intravesical therapy

    PubMed Central

    Lin, Mei-Yi; Chiang, Su-Yin; Li, Yi-Zhen; Chen, Mei-Fang; Chen, Yueh-Sheng; Wu, Jin-Yi; Liu, Yi-Wen

    2016-01-01

    Radix Paeoniae Rubra (RPR) is the dried root of Paeonia lactiflora Pallas and Paeonia veitchii Lynch, and is a herbal medicine that is widely used in traditional Chinese medicine for the treatment of blood-heat and blood-stasis syndrome, similarly to Cortex Moutan. The present study identified the same three components in RPR and Cortex Moutan extracts. In addition, it has been reported that RPR has an anti-cancer effect. Bladder cancer is the seventh most common type of cancer worldwide. Due to the high recurrence rate, identifying novel drugs for bladder cancer therapy is essential. In the present study, RPR extract was evaluated as a bladder cancer therapy in vitro and in vivo. The present results revealed that RPR extract reduced the cell viability of bladder cancer cells with a half maximal inhibitory concentration of 1–3 mg/ml, and had an extremely low cytotoxic effect on normal urothelial cells. Additionally, RPR decreased certain cell cycle populations, predominantly cells in the G1 phase, and caused a clear sub-G increase. In a mouse orthotopic bladder tumor model, intravesical application of RPR extract decreased the bladder tumor size without altering the blood biochemical parameters of the mice. In summary, the present results demonstrate the anti-proliferative properties of RPR extract on bladder cancer cells, and its anti-bladder tumor effect in vivo. Compared to Cortex Moutan extract, RPR extract may provide a more effective alternative therapeutic strategy for the intravesical therapy of superficial bladder cancer. PMID:27446367

  5. Anti-interleukin-6 therapy through application of a monogenic protein inhibitor via gene delivery

    PubMed Central

    Görtz, Dieter; Braun, Gerald S.; Maruta, Yuichi; Djudjaj, Sonja; van Roeyen, Claudia R.; Martin, Ina V.; Küster, Andrea; Schmitz-Van de Leur, Hildegard; Scheller, Jürgen; Ostendorf, Tammo; Floege, Jürgen; Müller-Newen, Gerhard

    2015-01-01

    Anti-cytokine therapies have substantially improved the treatment of inflammatory and autoimmune diseases. Cytokine-targeting drugs are usually biologics such as antibodies or other engineered proteins. Production of biologics, however, is complex and intricate and therefore expensive which might limit therapeutic application. To overcome this limitation we developed a strategy that involves the design of an optimized, monogenic cytokine inhibitor and the protein producing capacity of the host. Here, we engineered and characterized a receptor fusion protein, mIL-6-RFP-Fc, for the inhibition of interleukin-6 (IL-6), a well-established target in anti-cytokine therapy. Upon application in mice mIL-6-RFP-Fc inhibited IL-6-induced activation of the transcription factor STAT3 and ERK1/2 kinases in liver and kidney. mIL-6-RFP-Fc is encoded by a single gene and therefore most relevant for gene transfer approaches. Gene transfer through hydrodynamic plasmid delivery in mice resulted in hepatic production and secretion of mIL-6-RFP-Fc into the blood in considerable amounts, blocked hepatic acute phase protein synthesis and improved kidney function in an ischemia and reperfusion injury model. Our study establishes receptor fusion proteins as promising agents in anti-cytokine therapies through gene therapeutic approaches for future targeted and cost-effective treatments. The strategy described here is applicable for many cytokines involved in inflammatory and other diseases. PMID:26423228

  6. Anti-angiogenic therapy increases intratumoral adenovirus distribution by inducing collagen degradation.

    PubMed

    Thaci, B; Ulasov, I V; Ahmed, A U; Ferguson, S D; Han, Y; Lesniak, M S

    2013-03-01

    Conditionally replicating adenoviruses (CRAd) are a promising class of gene therapy agents that can overcome already known glioblastoma (GBM) resistance mechanisms but have limited distribution upon direct intratumoral (i.t.) injection. Collagen bundles in the extracellular matrix (ECM) have an important role in inhibiting virus distribution. In fact, ECM pre-treatment with collagenases improves virus distributions to tumor cells. Matrix metalloproteinases (MMPs) are an endogenous class of collagenases secreted by tumor cells whose function can be altered by different drugs including anti-angiogenic agents, such as bevacizumab. In this study we hypothesized that upregulation of MMP activity during anti-angiogenic therapy can improve CRAd-S-pk7 distribution in GBM. We find that MMP-2 activity in human U251 GBM xenografts increases (*P=0.03) and collagen IV content decreases (*P=0.01) during vascular endothelial growth factor (VEGF-A) antibody neutralization. After proving that collagen IV inhibits CRAd-S-pk7 distribution in U251 xenografts (Spearman rho=-0.38; **P=0.003), we show that VEGF-blocking antibody treatment followed by CRAd-S-pk7 i.t. injection reduces U251 tumor growth more than each individual agent alone (***P<0.0001). Our data propose a novel approach to improve virus distribution in tumors by relying on the early effects of anti-angiogenic therapy. PMID:22673390

  7. Angiostatic treatment prior to chemo- or photodynamic therapy improves anti-tumor efficacy.

    PubMed

    Weiss, Andrea; Bonvin, Débora; Berndsen, Robert H; Scherrer, Edoardo; Wong, Tse J; Dyson, Paul J; Griffioen, Arjan W; Nowak-Sliwinska, Patrycja

    2015-01-01

    Tumor vasculature is known to be poorly organized leading to increased leakage of molecules to the extravascular space. This process can potentially increase interstitial fluid pressure impairing intra-tumoral blood flow and oxygen supply, and can affect drug uptake. Anti-angiogenic therapies are believed to reduce vascular permeability, potentially reducing interstitial fluid pressure and improving the extravasation of small molecule-based chemotherapeutics. Here we show that pretreatment of human ovarian carcinoma tumors with sub-optimal doses of the VEGFR targeting tyrosine kinase inhibitor axitinib, but not the EGFR targeting kinase inhibitor erlotinib, induces a transient period of increased tumor oxygenation. Doxorubicin administered within this window was found to enter the extravascular tumor space more rapidly compared to doxorubicin when applied alone or outside this time window. Treatment with the chemotherapeutics, doxorubicin and RAPTA-C, as well as applying photodynamic therapy during this period of elevated oxygenation led to enhanced tumor growth inhibition. Improvement of therapy was not observed when applied outside the window of increased oxygenation. Taken together, these findings further confirm the hypothesis of angiostasis-induced vascular normalization and also help to understand the interactions between anti-angiogenesis and other anti-cancer strategies. PMID:25758612

  8. Anti-interleukin-6 therapy through application of a monogenic protein inhibitor via gene delivery.

    PubMed

    Görtz, Dieter; Braun, Gerald S; Maruta, Yuichi; Djudjaj, Sonja; van Roeyen, Claudia R; Martin, Ina V; Küster, Andrea; Schmitz-Van de Leur, Hildegard; Scheller, Jürgen; Ostendorf, Tammo; Floege, Jürgen; Müller-Newen, Gerhard

    2015-01-01

    Anti-cytokine therapies have substantially improved the treatment of inflammatory and autoimmune diseases. Cytokine-targeting drugs are usually biologics such as antibodies or other engineered proteins. Production of biologics, however, is complex and intricate and therefore expensive which might limit therapeutic application. To overcome this limitation we developed a strategy that involves the design of an optimized, monogenic cytokine inhibitor and the protein producing capacity of the host. Here, we engineered and characterized a receptor fusion protein, mIL-6-RFP-Fc, for the inhibition of interleukin-6 (IL-6), a well-established target in anti-cytokine therapy. Upon application in mice mIL-6-RFP-Fc inhibited IL-6-induced activation of the transcription factor STAT3 and ERK1/2 kinases in liver and kidney. mIL-6-RFP-Fc is encoded by a single gene and therefore most relevant for gene transfer approaches. Gene transfer through hydrodynamic plasmid delivery in mice resulted in hepatic production and secretion of mIL-6-RFP-Fc into the blood in considerable amounts, blocked hepatic acute phase protein synthesis and improved kidney function in an ischemia and reperfusion injury model. Our study establishes receptor fusion proteins as promising agents in anti-cytokine therapies through gene therapeutic approaches for future targeted and cost-effective treatments. The strategy described here is applicable for many cytokines involved in inflammatory and other diseases. PMID:26423228

  9. Effects of Narrow Band Ultraviolet B on Serum Levels of Vascular Endothelial Growth Factor and Interleukin-8 in Patients with Psoriasis.

    PubMed

    Chen, Hong-Quan; Li, Xia; Tang, Rong

    2016-01-01

    The aim of this study was to investigate the effects of narrow band ultraviolet B (NB-UVB) therapy on serum levels of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) in patients with psoriasis. Relevant Chinese and English scientific literature databases were searched to identify studies published before November, 2013 that included serum VEGF and IL-8 levels in patients with psoriasis. The studies retrieved from database searches were screened on the basis of predefined selection criteria, and data from finally selected studies were extracted for meta-analysis. Analyses were conducted using STATA 12.0 software. Our systematic search resulted in retrieval of 700 studies (500 studies in Chinese, 200 studies in English), and after a multistep screening process, 13 studies met the inclusion criteria and were enrolled for meta-analysis. The 13 studies contained a combined total of 400 patients with psoriasis and 221 healthy controls. The results of meta-analysis revealed that healthy controls exhibited significantly lower serum level of VEGF, compared to patients with psoriasis before therapy. After NB-UVB, VEGF levels were significantly decreased in patients with psoriasis, as compared to their pretherapy VEGF levels. Although no statistically significant differences were detected in IL-8 serum levels between patients with psoriasis and healthy controls before therapy, after NB-UVB therapy, the serum IL-8 levels in patients with psoriasis were markedly decreased. Corresponding reductions in the psoriasis area and severity index scores of patients with psoriasis were observed after NB-UVB treatment. Our results revealed that NB-UVB therapy significantly decreased the serum levels of VEGF and IL-8 in patients with psoriasis. Furthermore, VEGF and IL-8 levels correlated with disease status, indicating that they are sensitive biomarkers for evaluating the effectiveness of psoriasis therapy. PMID:26308328

  10. Selected anti-tumor vaccines merit a place in multimodal tumor therapies

    PubMed Central

    Weiss, Eva-Maria; Wunderlich, Roland; Ebel, Nina; Rubner, Yvonne; Schlücker, Eberhard; Meyer-Pittroff, Roland; Ott, Oliver J.; Fietkau, Rainer; Gaipl, Udo S.; Frey, Benjamin

    2012-01-01

    Multimodal approaches are nowadays successfully applied in cancer therapy. Primary locally acting therapies such as radiotherapy (RT) and surgery are combined with systemic administration of chemotherapeutics. Nevertheless, the therapy of cancer is still a big challenge in medicine. The treatments often fail to induce long-lasting anti-tumor responses. Tumor recurrences and metastases result. Immunotherapies are therefore ideal adjuncts to standard tumor therapies since they aim to activate the patient's immune system against malignant cells even outside the primary treatment areas (abscopal effects). Especially cancer vaccines may have the potential both to train the immune system against cancer cells and to generate an immunological memory, resulting in long-lasting anti-tumor effects. However, despite promising results in phase I and II studies, most of the concepts finally failed. There are some critical aspects in development and application of cancer vaccines that may decide on their efficiency. The time point and frequency of medication, usage of an adequate immune adjuvant, the vaccine's immunogenic potential, and the tumor burden of the patient are crucial. Whole tumor cell vaccines have advantages compared to peptide-based ones since a variety of tumor antigens (TAs) are present. The master requirements of cell-based, therapeutic tumor vaccines are the complete inactivation of the tumor cells and the increase of their immunogenicity. Since the latter is highly connected with the cell death modality, the inactivation procedure of the tumor cell material may significantly influence the vaccine's efficiency. We therefore also introduce high hydrostatic pressure (HHP) as an innovative inactivation technology for tumor cell-based vaccines and outline that HHP efficiently inactivates tumor cells by enhancing their immunogenicity. Finally studies are presented proving that anti-tumor immune responses can be triggered by combining RT with selected immune

  11. The Development of Metabolic Risk Factors After the Initiation of the Second Line Anti- Retroviral Therapy

    PubMed Central

    Mittal, Apoorva; Achappa, Basavaprabhu; Madi, Deepak; Chowta, Mukta N; Ramapuram, John T; Rao, Satish; Unnikrishnan, B; Mahalingam, Soundarya

    2013-01-01

    Background and objective: A Highly Active Anti-Retroviral Therapy (HAART) is accompanied with several metabolic effects like adipose redistribution and insulin resistance. In this study, we evaluated the association between a HAART and lipodystrophy. Methods: A cross sectional study, whose subjects were Human Immunodeficiency Virus (HIV) infected patients, was conducted at a tertiary care hospital in south India. Among these, 27 were on protease inhibitors for at-least 6 months and 13 were drug naive patients. The assessments of lipodystrophy, fasting blood sugar and the fasting lipid profile were done and these parameters were compared in the two groups. Results: The analysis of the data which was collected, showed an elevation in the total cholesterol levels in the individuals who were on the protease inhibitors versus the drug naive patients. There was a significant elevation in the Low Density Lipoprotein (LDL) cholesterol levels and a decrease in High Density Lipoprotein (HDL) cholesterol levels in the individuals who were on protease inhibitors. It was also observed that the HDL cholesterol levels decreased with an increase in the duration of the therapy. The LDL cholesterol levels increased with the duration of the therapy. Conclusion: The human immunodeficiency virus infection is itself related to the metabolic complications which are aggravated on the use of second line anti retroviral therapy. Therefore, after initiating the treatment with protease inhibitors, a periodic evaluation of the serum lipid levels and the blood sugar profile should be done as a standard care. PMID:23542168

  12. Combinatorial Anti-HIV Gene Therapy: Using a Multi-Pronged Approach to Reach Beyond HAART

    PubMed Central

    Peterson, Christopher W; Younan, Patrick; Jerome, Keith R; Kiem, Hans-Peter

    2013-01-01

    The “Berlin Patient,” who maintains suppressed levels of HIV viremia in the absence of antiretroviral therapy, continues to be a standard bearer in HIV eradication research. However, the unique circumstances surrounding his functional cure are not applicable to most HIV+ patients. To achieve a functional or sterilizing cure in a greater number of infected individuals worldwide, combinatorial treatments, targeting multiple stages of the viral life cycle, will be essential. Several anti-HIV gene therapy approaches have recently been explored, including disruption of the CCR5 and CXCR4 coreceptor loci in CD4+ T-cells and CD34+ hematopoietic stem cells. However, less is known about the efficacy of these strategies in patients and more relevant HIV model systems such as nonhuman primates. Combinatorial approaches, including genetic disruption of integrated provirus, functional enhancement of endogenous restriction factors, and/or the use of pharmacological adjuvants, could amplify the anti-HIV effects of CCR5/CXCR4 gene disruption. Importantly, delivering gene disruption molecules to genetic sites of interest will likely require optimization on a cell type-by-cell type basis. In this review, we highlight the most promising gene therapy approaches to combat HIV infection, methods to deliver these therapies to hematopoietic cells, and emphasize the need to target viral replication pre- and post-entry in order to mount a suitably robust defense against spreading infection. PMID:23364313

  13. Anti-rods/rings autoantibody generation in hepatitis C patients during interferon-α/ribavirin therapy.

    PubMed

    Keppeke, Gerson Dierley; Calise, S John; Chan, Edward K L; Andrade, Luis Eduardo C

    2016-02-14

    Chronic inflammation associated with hepatitis C virus (HCV) infection can lead to disabling liver diseases with progression to liver cirrhosis and hepatocellular carcinoma. Despite the recent availability of more effective and less toxic therapeutic options, in most parts of the world the standard treatment consists of a weekly injection of pegylated interferon α (IFN-α) together with a daily dose of ribavirin. HCV patients frequently present circulating non-organ-specific autoantibodies demonstrating a variety of staining patterns in the indirect immunofluorescence assay for antinuclear antibodies (ANA). Between 20% to 40% of HCV patients treated with IFN-α and ribavirin develop autoantibodies showing a peculiar ANA pattern characterized as rods and rings (RR) structures. The aim of this article is to review the recent reports regarding RR structures and anti-rods/rings (anti-RR) autoantibody production by HCV patients after IFN-α/ribavirin treatment. Anti-RR autoantibodies first appear around the sixth month of treatment and reach a plateau around the twelfth month. After treatment completion, anti-RR titers decrease/disappear in half the patients and remain steady in the other half. Some studies have observed a higher frequency of anti-RR antibodies in relapsers, i.e., patients in which circulating virus reappears after initially successful therapy. The main target of anti-RR autoantibodies in HCV patients is inosine-5'-monophosphate dehydrogenase 2 (IMPDH2), the rate-limiting enzyme involved in the guanosine triphosphate biosynthesis pathway. Ribavirin is a direct IMPDH2 inhibitor and is able to induce the formation of RR structures in vitro and in vivo. In conclusion, these observations led to the hypothesis that anti-RR autoantibody production is a human model of immunologic tolerance breakdown that allows us to explore the humoral autoimmune response from the beginning of the putative triggering event: exposure to ribavirin and interferon. PMID:26877604

  14. Napkin psoriasis--case report.

    PubMed

    Creţu, Anca; Crihan, Elena; Oanţă, A; Sălăvăstru, Carmen; Brănişteanu, D; Brănişteanu, Daciana Elena

    2014-01-01

    Psoriasis is a chronic inflammatory disease that can affect up to 1% of children. Genetic (family history of psoriasis) and environmental factors (bacterial or viral infections, stress, and trauma) are frequently involved in its occurrence. Napkin psoriasis is a particular form of psoriasis affecting mainly children younger than 2 years of age and can be classified together with other diseases under diaper rash. We present the case of a 4-month-old infant, born at term, naturally, weight and height within the normal range, who was brought to the Dermatology Clinic for the occurrence of erythematosquamous lesions in the anogenital area, buttocks and upper third of the thighs, with subsequent dissemination of lesions. The onset of symptoms began a few days after a respiratory tract infection. Initially he received treatment with systemic antibiotic and topical corticosteroid and antibiotic with unfavorable outcome. Laboratory tests revealed iron-deficiency anemia, leukocytosis, thrombocytosis, accelerated ESR, marked hepatic cytolysis, hyperphosphatemia and nasal carriage of Staphylococcus aureus. A systemic antihistamine and nonspecific desensitization treatment was administered. Topical treatment consisted in the removal of predisposing factors and irritants (diaper, urine) by rigorous hygiene, application of topical non-fluorinated cortico-steroid and use of emollients, with favorable course of the lesions. The peculiarity of the case is that the diagnosis of psoriasis was based on history, physical examination and laboratory tests, in the absence of a pathology examination to confirm the diagnosis. Pathology examination could not be performed due to patient's age as biopsy required general anesthesia. PMID:25581961

  15. Epidermal Th22 and Tc17 cells form a localized disease memory in clinically healed psoriasis.

    PubMed

    Cheuk, Stanley; Wikén, Maria; Blomqvist, Lennart; Nylén, Susanne; Talme, Toomas; Ståhle, Mona; Eidsmo, Liv

    2014-04-01

    Psoriasis is a common and chronic inflammatory skin disease in which T cells play a key role. Effective treatment heals the skin without scarring, but typically psoriasis recurs in previously affected areas. A pathogenic memory within the skin has been proposed, but the nature of such site-specific disease memory is unknown. Tissue-resident memory T (TRM) cells have been ascribed a role in immunity after resolved viral skin infections. Because of their localization in the epidermal compartment of the skin, TRM may contribute to tissue pathology during psoriasis. In this study, we investigated whether resolved psoriasis lesions contain TRM cells with the ability to maintain and potentially drive recurrent disease. Three common and effective therapies, narrowband-UVB treatment and long-term biologic treatment systemically inhibiting TNF-α or IL-12/23 signaling were studied. Epidermal T cells were highly activated in psoriasis and a high proportion of CD8 T cells expressed TRM markers. In resolved psoriasis, a population of cutaneous lymphocyte-associated Ag, CCR6, CD103, and IL-23R expressing epidermal CD8 T cells was highly enriched. Epidermal CD8 T cells expressing the TRM marker CD103 responded to ex vivo stimulation with IL-17A production and epidermal CD4 T cells responded with IL-22 production after as long as 6 y of TNF-α inhibition. Our data suggest that epidermal TRM cells are retained in resolved psoriasis and that these cells are capable of producing cytokines with a critical role in psoriasis pathogenesis. We provide a potential mechanism for a site-specific T cell-driven disease memory in psoriasis. PMID:24610014

  16. Pathophysiological basis of systemic treatments in psoriasis.

    PubMed

    Volc, Sebastian; Ghoreschi, Kamran

    2016-06-01

    Over the past 15 years, the spectrum of systemic antipsoriatic treatments has dramatically expanded. Until the end of the last millennium, systemic therapy had been restricted to four oral agents: methotrexate, cyclosporine, acitretin, and fumaric acid esters. Today, there are additionally seven biologics and one new oral antipsoriatic drug, as well as the first available biosimilars. Six more biologics with novel target structures and at least four biosimilars are currently being developed (phase III). This progress has been based on new insights into the pathogenesis of psoriasis, in which tumor necrosis factor and especially Th17 immune responses with their associated cytokines interleukin 23 and 17 play a key role. The development of new-generation biologics as well as immunomodulatory small molecules can be attributed to these pathophysiological findings. Phosphodiesterase 4 inhibitors, dimethyl fumarate, and Janus kinase inhibitors all interact with Th17 immune responses. Some of these drugs are in advanced clinical development and are also beneficial in psoriatic arthritis. Today, psoriasis and psoriatic arthritis therefore rank among the most readily treatable inflammatory autoimmune disorders. Dermatology is increasingly becoming a specialty of modern targeted immunotherapies. PMID:27240060

  17. Biologics and Pediatric Generalized Pustular Psoriasis: An Emerging Therapeutic Trend

    PubMed Central

    Mattes, Monica

    2016-01-01

    Generalized pustular psoriasis (GPP) is a rare form of childhood psoriasis, often requiring systemic therapy, which is challenging as there is a paucity of randomized controlled trials and standardized guidelines. Biologic agents have been used in adults and in pediatric plaque psoriasis, but evidence regarding their efficacy in pediatric GPP has slowly become available. The objective of this study is to summarize and compare the efficacy and safety of biologic agents, such as etanercept, infliximab, and adalimumab, in the treatment of pediatric GPP. A PubMed literature review was conducted and 12 studies met the inclusion criteria for analysis. After reviewing the efficacy of these drugs in pediatric GPP patients and their safety in the use of other pediatric conditions, etanercept was identified as a possible first-line biologic agent for pediatric psoriasis, including GPP, followed by infliximab and adalimumab. In conclusion, several case reports have documented the successful use of biologic agents in refractory cases of pediatric GPP, but clinical trials are needed to gain a better understanding of the efficacy and side effect profile in this population. PMID:27462478

  18. New treatments for psoriasis: which biologic is best?

    PubMed

    Nelson, Andrew A; Pearce, Daniel J; Fleischer, Alan B; Balkrishnan, Rajesh; Feldman, Steven R

    2006-01-01

    Psoriasis is a chronic, debilitating disease affecting not only the skin, but also having a significant impact on a patient's quality of life. The treatment of severe psoriasis is quite challenging due to the chronic, relapsing nature of the disease and the difficulties inherent in treatment planning. Though the biologics are perhaps the most promising of available psoriasis treatments, the decision to institute a given therapy may be fraught with complexity for the clinician. Patients now hear of these promising new treatments for psoriasis via print, television and radio advertising; they frequently come to their physician asking if they are eligible for any of these agents and, if so, 'which biologic is best?'. This paper attempts to determine the ideal biologic agent based upon several parameters: FDA- and EU-approved indications, therapeutic efficacy, impact on quality of life, cost-effectiveness, and safety profile. Certainly the physician is central to medical decision-making, though ultimately patient preference may play the largest role in determining the 'best' biologic agent. There is no single ideal biologic for all patients and a physician's job is to educate patients on the relative advantages and disadvantages of each agent. Through informed discussion, the clinician can help each individual patient decide which biologic agent is ideal for them. PMID:16766334

  19. First case report of exacerbated ulcerative colitis after anti-interleukin-6R salvage therapy

    PubMed Central

    Atreya, Raja; Billmeier, Ulrike; Rath, Timo; Mudter, Jonas; Vieth, Michael; Neumann, Helmut; Neurath, Markus F

    2015-01-01

    We present the case of a 53-year-old woman with long-standing ulcerative colitis and severe, steroid-dependent disease course unresponsive to treatment with azathioprine, methotrexate, anti-TNF antibodies (infliximab, adalimumab) and tacrolimus, who refused colectomy as a therapeutic option. As the pro-inflammatory cytokine interleukin-6 (IL-6) had been identified as a crucial regulator in the immunopathogenesis of inflammatory bowel diseases, we treated the patient with biweekly intravenous infusions of an anti-IL-6R antibody (tocilizumab) for 12 wk. However, no clinical improvement of disease activity was noted. In fact, endoscopic, histological and endomicroscopic assessment demonstrated exacerbation of mucosal inflammation and ulcer formation upon anti-IL-6R therapy. Mechanistic studies revealed that tocilizumab treatment failed to suppress intestinal IL-6 production, impaired epithelial barrier function and induced production of pro-inflammatory cytokines such as TNF, IL-21 and IFN-γ. Inhibition of IL-6 by tocilizumab had no clinical benefit in this patient with intractable ulcerative colitis and even led to exacerbation of mucosal inflammation. Our findings suggest that anti-IL-6R antibody therapy may lead to aggravation of anti-TNF resistant ulcerative colitis. When targeting IL-6, the differential responsiveness of target cells has to be taken into account, as IL-6 on the one side promotes acute and chronic mucosal inflammation via soluble IL-6R signaling but on the other side also strongly contributes to epithelial cell survival via membrane bound IL-6R signaling. PMID:26668517

  20. Optimizing the sequence of anti-EGFR-targeted therapy in EGFR-mutant lung cancer.

    PubMed

    Meador, Catherine B; Jin, Hailing; de Stanchina, Elisa; Nebhan, Caroline A; Pirazzoli, Valentina; Wang, Lu; Lu, Pengcheng; Vuong, Huy; Hutchinson, Katherine E; Jia, Peilin; Chen, Xi; Eisenberg, Rosana; Ladanyi, Marc; Politi, Katerina; Zhao, Zhongming; Lovly, Christine M; Cross, Darren A E; Pao, William

    2015-02-01

    Metastatic EGFR-mutant lung cancers are sensitive to the first- and second-generation EGFR tyrosine kinase inhibitors (TKIs) gefitinib, erlotinib, and afatinib, but resistance develops. Acquired resistance to gefitinib or erlotinib occurs most commonly (>50%) via the emergence of a second-site EGFR mutation, T790M. Two strategies to overcome T790M-mediated resistance are dual inhibition of EGFR with afatinib plus the anti-EGFR antibody cetuximab (A+C), or mutant-specific EGFR inhibition with AZD9291. A+C and AZD9291 are now also being tested as first-line therapies, but whether these therapies will extend progression-free survival or induce more aggressive forms of resistance in this setting remains unknown. We modeled resistance to multiple generations of anti-EGFR therapies preclinically to understand the effects of sequential treatment with anti-EGFR agents on drug resistance and determine the optimal order of treatment. Using a panel of erlotinib/afatinib-resistant cells, including a novel patient-derived cell line (VP-2), we found that AZD9291 was more potent than A+C at inhibiting cell growth and EGFR signaling in this setting. Four of four xenograft-derived A+C-resistant cell lines displayed in vitro and in vivo sensitivity to AZD9291, but four of four AZD9291-resistant cell lines demonstrated cross-resistance to A+C. Addition of cetuximab to AZD9291 did not confer additive benefit in any preclinical disease setting. This work, emphasizing a mechanistic understanding of the effects of therapies on tumor evolution, provides a framework for future clinical trials testing different treatment sequences. This paradigm is applicable to other tumor types in which multiple generations of inhibitors are now available. PMID:25477325

  1. Optimizing the sequence of anti-EGFR targeted therapy in EGFR-mutant lung cancer

    PubMed Central

    Meador, Catherine B.; Jin, Hailing; de Stanchina, Elisa; Nebhan, Caroline A.; Pirazzoli, Valentina; Wang, Lu; Lu, Pengcheng; Vuong, Huy; Hutchinson, Katherine E.; Jia, Peilin; Chen, Xi; Eisenberg, Rosana; Ladanyi, Marc; Politi, Katerina; Zhao, Zhongming; Lovly, Christine M.; Cross, Darren A. E.; Pao, William

    2015-01-01

    Metastatic EGFR-mutant lung cancers are sensitive to the first- and second- generation EGFR tyrosine kinase inhibitors (TKIs), gefitinib, erlotinib, and afatinib, but resistance develops. Acquired resistance (AR) to gefitinib or erlotinib occurs most commonly (>50%) via the emergence of a second-site EGFR mutation, T790M. Two strategies to overcome T790M-mediated resistance are dual inhibition of EGFR with afatinib plus the anti-EGFR antibody, cetuximab (A+C), or mutant-specific EGFR inhibition with AZD9291. A+C and AZD9291 are now also being tested as first-line therapies, but whether these therapies will extend progression-free survival or induce more aggressive forms of resistance in this setting remains unknown. We modeled resistance to multiple generations of anti-EGFR therapies preclinically in order to understand the effects of sequential treatment with anti-EGFR agents on drug resistance and determine the optimal order of treatment. Using a panel of erlotinib/afatinib-resistant cells including a novel patient-derived cell line (VP-2), we found that AZD9291 was more potent than A+C at inhibiting cell growth and EGFR signaling in this setting. 4 of 4 xenograft-derived A+C-resistant cell lines displayed in vitro and in vivo sensitivity to AZD9291, but 4 of 4 AZD9291-resistant cell lines demonstrated cross-resistance to A+C. Addition of cetuximab to AZD9291 did not confer additive benefit in any preclinical disease setting. This work, emphasizing a mechanistic understanding of the effects of therapies on tumor evolution, provides a framework for future clinical trials testing different treatment sequences. This paradigm is applicable to other tumor types in which multiple generations of inhibitors are now available. PMID:25477325

  2. From basic research to biological treatments: psoriasis publications over the past 15 years.

    PubMed

    Pavlovsky, L; Mimouni, F B; Hodak, E; David, M; Mimouni, D

    2009-07-01

    In the past few decades, great progress has been made in psoriasis research, culminating with the development of new, biological treatments. We designed this study to test the hypothesis that there is a linear increase in psoriasis publications over time. We evaluated all PubMed articles from 1 January 1993 to 31 December 2007. We categorized the search into basic science, traditional therapy and new biological treatments. We used regression analysis to determine the effect of year of publication upon number of publications of each type. There was a significant quadratic increase in the number of all types of psoriasis publications, with basic science-related publications being greatest, followed by relevant clinical publications. We conclude that better understanding of psoriasis immunopathology has led to a significant yearly increase in clinical studies, contributing approximately 60% of studies in the entire field of dermatology reports. PMID:19438559

  3. Essential Truths for the Care and Management of Moderate-to-Severe Psoriasis.

    PubMed

    Blauvelt, Andrew; Armstrong, April W; Krueger, Gerald G

    2015-08-01

    Psoriasis is a systemic inflammatory disease. Effective management requires treatment with agents targeting inflammation in skin, joints, and other tissues. Biologics for psoriasis are directed at more specific targets, have a better safety profile, are better tolerated, and are more effective than conventional systemic agents. Despite these advances, many patients with psoriasis remain undertreated, and overall patient satisfaction remains low. The dichotomy between ideal therapeutic outcomes and suboptimal outcomes (which are currently commonplace) is likely largely due to misperceptions about psoriasis and biologic treatments. This article discusses these misperceptions, including the notions that psoriasis is a benign disorder, and that conventional systemic therapies are safer than biologics and adequate for most patients with moderate-to-severe disease. We present practical and evidence-based discussions to refute these misconceptions and provide useful resources for providers and patients that support access to advanced therapies. We believe that biologics represent optimal treatment for most patients with moderate-to-severe psoriasis, and until more effective approaches are generated, these efficacious and target-specific approaches should become the standard of care. PMID:26267724

  4. Manifestation of psoriasis in the oral cavity.

    PubMed

    Fatahzadeh, Mahnaz

    2016-03-01

    Despite the common prevalence of cutaneous psoriasis, the existence of manifestations in the oral cavity is subject to controversy. In this article, dermatologic psoriasis is reviewed, and a patient with generalized, symptomatic oral mucosal erythema resembling atrophic candidiasis synchronous with flare of chronic skin psoriasis is described. Diagnostic work up and therapeutic response supported that these mucosal findings were the oral counterpart of cutaneous disease. Dental providers should be familiar with the signs and symptoms of oral psoriasis, institute appropriate preventive measures, and provide palliation directed at symptomatic oral changes of psoriasis. PMID:26665263

  5. Psoriatic arthritis and psoriasis: differential diagnosis.

    PubMed

    Napolitano, Maddalena; Caso, Francesco; Scarpa, Raffaele; Megna, Matteo; Patrì, Angela; Balato, Nicola; Costa, Luisa

    2016-08-01

    Psoriasis frequency ranges from 1 to 3 % in white population, and arthritis occurs in 10-40 % of psoriasis patients, representing a relevant health issue. Psoriatic arthritis (PsA) is an inflammatory arthropathy, associated with psoriasis, in which ocular-, intestinal-, metabolic-, and cardiovascular-related manifestations can variably coexist. In order to favor early PsA and psoriasis diagnosis, it is crucial to rule out other conditions that can resemble the disease and delay appropriate therapeutic approach. Therefore, the aim of this review is to focus on PsA and psoriasis differential diagnosis. PMID:27156076

  6. Anti-angiogenic therapy via cationic liposome-mediated systemic siRNA delivery.

    PubMed

    Tagami, Tatsuaki; Suzuki, Takuya; Matsunaga, Mariko; Nakamura, Kazuya; Moriyoshi, Naoto; Ishida, Tatsuhiro; Kiwada, Hiroshi

    2012-01-17

    siRNA has been touted as a therapeutic molecule against genetic diseases, which include cancers. But several challenging issues remain in order to achieve efficient systemic siRNA delivery and a sufficient therapeutic effect for siRNA in vivo. Cationic liposome shows promise as a carrier for nucleic acids, as it can selectively bind to angiogenic tumor blood vessels. In this way, anti-angiogenic therapy via cationic liposome-mediated systemic siRNA delivery could be achieved in cancer therapy. In the present study, we proved our assumption by preparing various kinds of polyethylene glycol (PEG)-coated siRNA/cationic liposome complexes (siRNA-lipoplexes) and screening the avidity of these siRNA-lipoplexes upon angiogenic tumor blood vessels by means of a murine dorsal air sac (DAS) model. The lipoplex, having a lipid composition of DC-6-14/POPC/CHOL/DOPE/mPEG(2000)-DSPE=20/30/30/20/5 (molar ratio) and a charge ratio of cationic liposome and siRNA=3.81 (+/-), showed a higher binding index to newly formed blood vessels. Systemic injection with the lipoplex containing siRNA for the Argonaute2 gene (apoptosis-inducible siRNA) resulted in significant anti-tumor effect without severe side effects in mice with Lewis lung carcinoma. Our results indicate that the PEGylated cationic liposome-mediated systemic delivery of cytotoxic siRNA achieves anti-angiogenesis, resulting in the suppression of tumor growth. PMID:22101286

  7. HIF inhibitors for ischemic retinopathies and cancers: options beyond anti-VEGF therapies.

    PubMed

    Subhani, Saima; Vavilala, Divya Teja; Mukherji, Mridul

    2016-07-01

    Aberrant activation of the hypoxia inducible factor (HIF) pathway causing overexpression of angiogenic genes, like vascular endothelial growth factor (VEGF), is one of the underlying causes of ocular neovascularization (NV) and metastatic cancer. Consistently, along with surgical interventions, a number of anti-VEGF agents have been approved by FDA for the treatment of ocular neovascular diseases. These anti-VEGF agents, like ranibizumab/lucentis, have revolutionized the treatment in the past decade. However, substantial vision improvement is observed only in a subset of age-related macular degeneration patients receiving ranibizumab. Further, all current therapies are associated with limitations and side effects. For example, surgeries cause tissue destruction and inflammation while anti-VEGF therapies are expensive, require repeated administration, and offer temporary relief from vascular leakage. These factors impose significant cost and treatment burdens to both the patient and society. With an aging population in most western countries with a continually increasing number of patients on lifelong treatment for these retinal diseases, the focus of ocular drug development for neovascular diseases will be to improve efficacy while reducing treatment costs. Blocking the HIF pathway, a major regulator of ocular NV and cancer, offers an appealing therapeutic strategy. Therefore, this review summarizes HIF inhibitors that have been recently evaluated for the treatment of different cancers and ischemic retinopathies. PMID:27146677

  8. Sigma receptor-mediated targeted delivery of anti-angiogenic multifunctional nanodrugs for combination tumor therapy.

    PubMed

    Li, Yuanke; Wu, Yuanyuan; Huang, Leaf; Miao, Lei; Zhou, Jianping; Satterlee, Andrew Benson; Yao, Jing

    2016-04-28

    The potential of low molecular weight heparin (LMWH) in anti-angiogenic therapy has been tempered by poor in vivo delivery to the tumor cell and potentially harmful side effects, such as the risk of bleeding due to heparin's anticoagulant activity. In order to overcome these limitations and further improve the therapeutic effect of LMWH, we designed a novel combination nanosystem of LMWH and ursolic acid (UA), which is also an angiogenesis inhibitor for tumor therapy. In this system, an amphiphilic LMWH-UA (LHU) conjugate was synthesized and self-assembled into core/shell nanodrugs with combined anti-angiogenic activity and significantly reduced anticoagulant activity. Furthermore, DSPE-PEG-AA-modified LHU nanodrugs (A-LHU) were developed to facilitate the delivery of nanodrugs to the tumor. The anti-angiogenic activity of A-LHU was investigated both in vitro and in vivo. It was found that A-LHU significantly inhibited the tubular formation of human umbilical vein endothelial cells (HUVECs) (p<0.01) and the angiogenesis induced by basic fibroblast growth factor (bFGF) in a Matrigel plug assay (p<0.001). More importantly, A-LHU displayed significant inhibition on the tumor growth in B16F10-bearing mice in vivo. The level of CD31 and p-VEGFR-2 expression has demonstrated that the excellent efficacy of antitumor was associated with a decrease in angiogenesis. In conclusion, A-LHU nanodrugs are a promising multifunctional antitumor drug delivery system. PMID:26941036

  9. Psoriasis genetics: breaking the barrier

    PubMed Central

    Roberson, Elisha D.O.; Bowcock, Anne M.

    2010-01-01

    Psoriasis is a common incurable inflammatory skin disease affecting 2–3% of the European population. Psoriatic skin contains large numbers of immune cells which produce many cytokines, chemokines and inflammatory molecules. The epidermis divides much faster than normal and has a defective outer layer or barrier which under normal circumstances protects from infection and dehydration. Psoriatic skin is characterized by a distinct set of inflammation and epidermal proliferation and differentiation markers, and it has not been clear if the genetic basis of psoriasis is due to defects of the immune system or the skin. One genetic determinant lies within the major histocompatibility complex class 1 region. Genome-wide association studies have revealed genetic susceptibility factors that play a role in the formation of immune cells found in psoriasis lesions. Others affect epidermal proliferation and the formation of the skin’s barrier. Hence, genetic components of both the immune system and the epidermis predispose to disease. PMID:20692714

  10. Inverse psoriasis treated with ustekinumab.

    PubMed

    Campos, Manuel António; Varela, Paulo; Baptista, Armando; Moreira, Ana Isabel

    2016-01-01

    Inverse psoriasis is characterised by the involvement of flexural skin folds. This form of psoriasis has distinct clinical and therapeutic features. This report refers to the case of a 48-year-old Caucasian man who was observed in our department, with a clinically and biopsy proven diagnosis of inverse psoriasis. For 2 years, the patient was treated with different combinations of corticosteroids, vitamin D analogues and methotrexate, with no satisfactory response. Given the lack of a clinical response and comorbidities, latent tuberculosis was excluded, and we started treatment with ustekinumab. We chose this biological agent because the patient was a long-distance truck driver and refused the possibility of autoinjections. The patient underwent three ustekinumab injections, which resulted in significant improvement of pruritus, erythaematous lesions and quality of life. PMID:27222277

  11. [Psoriasis in a female chimpanzee].

    PubMed

    Biella, U; Haustein, U F; Seifert, S; Adler, J; Schüppel, K F; Eulenberger, K

    1991-05-01

    Psoriasis, a widespread genodermatosis in Homo sapiens, also appears in primates. We report on a female chimpanzee in Leipzig Zoo. After years of captivity the animal developed erythematosquamous, highly hyperkeratotic, lesions, some confluent, on the knees, elbows, back of the hands and feet and on the forearms and the seat, which showed histologically characteristic features of psoriasis. It may be that both previous infections and psychic stress resulting from social isolation had caused eruption of the disease. In the literature single cases of psoriasiform dermatoses have also been described in other species of monkeys and even in a springer spaniel. Nonetheless, the search for an animal model of psoriasis vulgaris is still going on. PMID:1874622

  12. Anti-TNFα therapy for inflammatory bowel diseases is associated with Epstein-Barr virus lytic activation.

    PubMed

    Lapsia, Sameer; Koganti, Siva; Spadaro, Salvatore; Rajapakse, Ramona; Chawla, Anupama; Bhaduri-McIntosh, Sumita

    2016-02-01

    Anti-TNFα therapy, known to suppress T-cell immunity, is increasingly gaining popularity for treatment of autoimmune diseases including inflammatory bowel diseases (IBD). T-cell suppression increases the risk of B-cell EBV-lymphoproliferative diseases and lymphomas. Since EBV-lytic activation is essential for development of EBV-lymphomas and there have been reports of EBV-lymphomas in patients treated with anti-TNFα therapy, we investigated if patients treated with anti-TNFα antibodies demonstrate greater EBV-lytic activity in blood. Peripheral blood mononuclear cells from 10 IBD patients solely on anti-TNFα therapy compared to 3 control groups (10 IBD patients not on immunosuppressive therapy, 10 patients with abdominal pain but without IBD, and 10 healthy subjects) were examined for the percentage of T-cells, EBV load and EBV-lytic transcripts. Patients on anti-TNFα therapy had significantly fewer T-cells, greater EBV load, and increased levels of transcripts from EBV-lytic genes of all kinetic classes compared to controls. Furthermore, exposure of EBV-infected B-cell lines to anti-TNFα antibodies resulted in increased levels of BZLF1 mRNA; BZLF1 encodes for ZEBRA, the viral latency-to-lytic cycle switch. Thus, IBD patients treated with anti-TNFα antibodies have greater EBV loads likely due to enhanced EBV-lytic gene expression and anti-TNFα antibodies may be sufficient to activate the EBV lytic cycle. Findings from this pilot study lay the groundwork for additional scientific and clinical investigation into the effects of anti-TNFα therapy on the life cycle of EBV, a ubiquitous oncovirus that causes lymphomas in the setting of immunocompromise. PMID:26307954

  13. Gene Therapy with Endogenous Inhibitors of Angiogenesis for Neovascular Age-Related Macular Degeneration: Beyond Anti-VEGF Therapy

    PubMed Central

    Prea, Selwyn M.; Chan, Elsa C.; Dusting, Gregory J.; Vingrys, Algis J.; Bui, Bang V.

    2015-01-01

    Age-related macular degeneration (AMD) is the leading cause of substantial and irreversible vision loss amongst elderly populations in industrialized countries. The advanced neovascular (or “wet”) form of the disease is responsible for severe and aggressive loss of central vision. Current treatments aim to seal off leaky blood vessels via laser therapy or to suppress vessel leakage and neovascular growth through intraocular injections of antibodies that target vascular endothelial growth factor (VEGF). However, the long-term success of anti-VEGF therapy can be hampered by limitations such as low or variable efficacy, high frequency of administration (usually monthly), potentially serious side effects, and, most importantly, loss of efficacy with prolonged treatment. Gene transfer of endogenous antiangiogenic proteins is an alternative approach that has the potential to provide long-term suppression of neovascularization and/or excessive vascular leakage in the eye. Preclinical studies of gene transfer in a large animal model have provided impressive preliminary results with a number of transgenes. In addition, a clinical trial in patients suffering from advanced neovascular AMD has provided proof-of-concept for successful gene transfer. In this mini review, we summarize current theories pertaining to the application of gene therapy for neovascular AMD and the potential benefits when used in conjunction with endogenous antiangiogenic proteins. PMID:25821585

  14. Anti-platelet therapy and aspirin resistance - clinically and chemically relevant?

    PubMed

    Rafferty, M; Walters, M R; Dawson, J

    2010-01-01

    Platelets play a central role in the pathogenesis of the atherothrombosis which ultimately causes myocardial infarction, stroke and peripheral vascular disease. Commonly used oral anti-platelet drugs include aspirin (an irreversible inhibitor of cyclo-oxygenase), clopidogrel (an ADP receptor antagonist), other thienopyridines such as ticlopidine and prasgruel, and dipyridamole (an inhibitor of adenosine reuptake and platelet phosphodiesterase). Newer agents are in development and one, ticagrelor, a reversible ADP receptor antagonist has shown promise. Despite their proven benefit, recurrent vascular events still occur in those taking anti-platelet drugs. This has led to the concept of anti-platelet resistance, most commonly aspirin resistance as this drug is the cornerstone of most regimens. The causes of aspirin resistance are numerous but potential mechanisms include lack of patient adherence, non COX-1 mediated thromboxane A2 synthesis, increased activity of alternate platelet activation pathways, interference of aspirin action by other drugs and probably pharmacogenetic factors. Measurement of platelet response to aspirin is made possible using a number of in-vitro laboratory assays of platelet function which include measurement of thromboxane A2 metabolites as well as newer point-of-care assays of platelet aggregation. The phenomenon of aspirin resistance is important as it raises the possibility of developing strategies to identify those who respond best to a particular anti-platelet regimen, or to development of newer anti-platelet therapies to which more patients respond. This review discusses important aspects of aspirin resistance both in terms of clinical medicine, alternative anti-platelet strategies, and the potential to overcome its various causes. PMID:21062249

  15. The skin in psoriasis: assessment and challenges.

    PubMed

    Oji, Vinzenz; Luger, Thomas A

    2015-01-01

    The coexistence of psoriasis arthritis (PsA) and psoriasis vulgaris in about 20% of patients with psoriasis leads to a need for rheumatologic-dermatologic team work. We summarise the role of dermatologists in assessment of the skin in psoriasis. Chronic plaque psoriasis must be differentiated from other subtypes such as generalised pustular psoriasis (GPP) or palmoplantar pustulosis (PPP). Therapeutic management is based on the evaluation of the disease severity. Quantitative scoring of skin severity includes calculation of the Psoriasis Area and Severity Index (PASI), body surface area (BSA) as well as the Dermatology Life Quality Index (DLQI). These scoring systems do not replace the traditional dermatologic medical history and physical examination of the patient. The skin should be examined for additional skin diseases; moreover, patients should be monitored for comorbidity, most importantly PsA and cardiovascular comorbidity. PMID:26472560

  16. Patterns of HER2 Gene Amplification and Response to Anti-HER2 Therapies

    PubMed Central

    Morancho, Beatriz; Zacarias-Fluck, Mariano; Zhang, Junjie; Martínez-Barriocanal, Águeda; Navarro Jiménez, Alexandra; Aura, Claudia; Burgues, Octavio; Lluch, Ana; Cortés, Javier; Nuciforo, Paolo; Rubio, Isabel T.; Marangoni, Elisabetta; Deeds, James; Boehm, Markus; Schlegel, Robert; Tabernero, Josep; Mosher, Rebecca; Arribas, Joaquín

    2015-01-01

    A chromosomal region that includes the gene encoding HER2, a receptor tyrosine kinase (RTK), is amplified in 20% of breast cancers. Although these tumors tend to respond to drugs directed against HER2, they frequently become resistant and resume their malignant progression. Gene amplification in double minutes (DMs), which are extrachromosomal entities whose number can be dynamically regulated, has been suggested to facilitate the acquisition of resistance to therapies targeting RTKs. Here we show that ~30% of HER2-positive tumors show amplification in DMs. However, these tumors respond to trastuzumab in a similar fashion than those with amplification of the HER2 gene within chromosomes. Furthermore, in different models of resistance to anti-HER2 therapies, the number of DMs containing HER2 is maintained, even when the acquisition of resistance is concomitant with loss of HER2 protein expression. Thus, both clinical and preclinical data show that, despite expectations, loss of HER2 protein expression due to loss of DMs containing HER2 is not a likely mechanism of resistance to anti-HER2 therapies. PMID:26075403

  17. Anti-angiogenic therapy increases intratumoral adenovirus distribution by inducing collagen degradation

    PubMed Central

    Thaci, Bart; Ulasov, Ilya V.; Ahmed, Atique U.; Ferguson, Sherise D.; Han, Yu; Lesniak, Maciej S.

    2012-01-01

    Conditionally replicating adenoviruses (CRAd) are a promising class of gene therapy agents that can overcome already known glioblastoma (GBM) resistance mechanisms but have limited distribution upon direct intratumoral (i.t.) injection. Collagen bundles in the extracellular matrix (ECM) play an important role in inhibiting virus distribution. In fact, ECM pre-treatment with collagenases improves virus distributions to tumor cells. Matrix metalloproteinases (MMPs) are an endogenous class of collagenases secreted by tumor cells whose function can be altered by different drugs including anti-angiogenic agents, such as bevacizumab. In this study we hypothesized that up-regulation of MMP activity during antiangiogenic therapy can improve CRAd-S-pk7 distribution in GBM. We find that MMP-2 activity in human U251 GBM xenografts increases (*p=0.03) and collagen IV content decreases (*p=0.01) during vascular endothelial growth factor (VEGF-A) antibody neutralization. After proving that collagen IV inhibits CRAd-S-pk7 distribution in U251 xenografts (Spearman rho= −0.38; **p=0.003), we show that VEGF blocking antibody treatment followed by CRAd-S-pk7 i.t. injection reduces U251 tumor growth more than each individual agent alone (***p<0.0001). Our data proposes a novel approach to improve virus distribution in tumors by relying on the early effects of anti-angiogenic therapy. PMID:22673390

  18. Safety of anti-tumor necrosis factor therapy during pregnancy in patients with inflammatory bowel disease.

    PubMed

    Androulakis, Ioannis; Zavos, Christos; Christopoulos, Panagiotis; Mastorakos, George; Gazouli, Maria

    2015-12-21

    Treatment of inflammatory bowel disease has significantly improved since the introduction of biological agents, such as infliximab, adalimumab, certolizumab pegol, and golimumab. The Food and Drug Administration has classified these factors in category B, which means that they do not demonstrate a fetal risk. However, during pregnancy fetuses are exposed to high anti-tumor necrosis factor (TNF) levels that are measurable in their plasma after birth. Since antibodies can transfer through the placenta at the end of the second and during the third trimesters, it is important to know the safety profile of these drugs, particularly for the fetus, and whether maintaining relapse of the disease compensates for the potential risks of fetal exposure. The limited data available for the anti-TNF drugs to date have not demonstrated any significant adverse outcomes in the pregnant women who continued their therapy from conception to the first trimester of gestation. However, data suggest that anti-TNFs should be discontinued during the third trimester, as they may affect the immunological system of the newborn baby. Each decision should be individualized, based on the distinct characteristics of the patient and her disease. Considering all the above, there is a need for more clinical studies regarding the effect of anti-TNF therapeutic agents on pregnancy outcomes. PMID:26715803

  19. Anti-Viral Therapy and Decreased Sexual Desire in Patients with Chronic Hepatitis C

    PubMed Central

    Hsieh, Po-Fan; Peng, Cheng-Yuan; Su, Kuan-Pin

    2016-01-01

    Purpose Peg-interferon (PegIFN)α2a or PegIFNα2b plus ribavirin (RBV) is the standard therapy for chronic hepatitis C virus (HCV) infection in Taiwan and Asia. It is commonly associated with adverse effects, but the issue of sexual and mental health is not well reported. This study aimed to evaluate the impact of anti-viral therapy with PegIFNα plus RBV on sexual desire and depression. Methods This prospective cohort study from 2009 to 2014 enrolled 181 patients with HCV who received PegIFNα2a (180 mcg/week) or PegIFNα2b (1.5 mcg/Kg/week) plus RBV (800–1200 mg/day) according to response-guide therapy for 24 to 48 weeks in a tertiary medical center. Patients with decreased sexual desire (DSD) before PegIFNα plus RBV were excluded. Patients were evaluated at baseline (week 0) and after 2, 4, 8, 12, 16, 20, and 24 weeks of PegIFNα plus RBV treatment using the structured Mini-International Neuropsychiatric Interview, for the diagnosis of a major depressive episode, and the 21-item Beck Depression Inventory (BDI), for monitoring depressive symptoms. The 21st item of the BDI was used to evaluate DSD. Results During therapy, 124 (68.5%) patients had DSD. The BDI score peaked at 14.8 weeks. The severity of DSD was greatest at 16 weeks of treatment. The average score of the 21st item of the BDI correlated with DSD. Depression history and the prevalence of subsequent major depressive disorder after anti-viral therapy was correlated to DSD (p = 0.05 and 0.001). Male patients complained of DSD more significantly than females (p = 0.031). Conclusions Decreased sexual desire is common but is usually neglected in patients with chronic hepatitis C undergoing anti-viral therapy, especially among male patients. Physicians must be monitoring the side effects of sexual health and depression. PMID:27505293

  20. Complementary and alternative medicine for psoriasis: what the dermatologist needs to know.

    PubMed

    Talbott, Whitney; Duffy, Nana

    2015-06-01

    Complementary and alternative medicine (CAM) use is common among patients with psoriasis. CAM modalities include traditional Chinese medicine (TCM), herbal therapies, dietary supplements, climatotherapy, and mind/body interventions. In this review, evidence from clinical trials investigating the efficacy of CAM for psoriasis is reviewed. There is a large amount of evidence from controlled trials that have shown that the combination of TCM with traditional therapies for psoriasis is more efficacious than traditional therapies alone. Herbal therapies that have the most evidence for efficacy are Mahonia aquifolium and indigo naturalis, while there is a smaller amount of evidence for aloe vera, neem, and extracts of sweet whey. Dietary supplementation in patients with psoriasis demonstrates consistent evidence supporting the efficacy of fish oil supplements. Zinc supplementation has not been shown to be effective; however, some evidence is available (albeit conflicting) for vitamin D, vitamin B12, and selenium supplementation. Overwhelming evidence supports the effectiveness of Dead Sea climatotherapy. Finally, mindfulness-based stress reduction can be helpful as adjuvant treatment of psoriasis. There are potential benefits to these modalities, but also potential side issues. Concerns with CAM include, but are not limited to, contamination of TCM products with heavy metals or corticosteroids, systemic toxicity or contact dermatitis from herbal supplements, and ultraviolet light-induced carcinomas from climatotherapy. Dermatologists should be aware of these benefits and side effects to allow for informed discussions with their patients. PMID:25904522

  1. Anti-tumor mechanism in IL-12 Gene therapy using liposomal bubbles and ultrasound

    NASA Astrophysics Data System (ADS)

    Suzuki, Ryo; Oda, Yusuke; Koshima, Risa; Hirata, Keiichi; Nomura, Tetsuya; Negishi, Yoichi; Utoguchi, Naoki; Nakagawa, Shinsaku; Maruyama, Kazuo

    2011-09-01

    Sonoporation combined with nano/microbubbles is an attractive technique for developing non-invasive and non-viral gene delivery systems. Previously, we developed novel ultrasound sensitive liposomes (Bubble liposomes) which contain the ultrasound imaging gas perfluoropropane. IL-12 corded plasmid DNA delivery into tumor tissue by sonoporation combined with Bubble liposomes was found to suppress tumor growth. In this study, we examined the mechanism of the anti-tumor effect in this IL-12 gene delivery. This therapeutic effect was T-cell dependent, requiring mainly CD8+ T lymphocytes in the effector phase, as confirmed by a mouse in vivo depletion assay. In addition, migration of CD8+ T cells was observed in the mice. These results suggest that CD8+ T lymphocytes play an important role in the anti-tumor effects of this IL-12 gene therapy.

  2. Autoimmune hemolytic anemia induced by anti-PD-1 therapy in metastatic melanoma.

    PubMed

    Kong, Benjamin Y; Micklethwaite, Kenneth P; Swaminathan, Sanjay; Kefford, Richard F; Carlino, Matteo S

    2016-04-01

    We report the occurrence of autoimmune hemolytic anemia in a patient receiving the anti-PD-1 monoclonal antibody, nivolumab, for metastatic melanoma in the presence of known red cell alloantibodies, despite having received prior ipilimumab without evidence of hemolysis. The patient had a history of multiple red cell alloantibodies and a positive direct antiglobulin test, identified at the time of a prior transfusion, which occurred before treatment with ipilimumab. The patient developed symptomatic warm autoimmune hemolytic anemia after four cycles of treatment with nivolumab. Clinical improvement was noted following cessation of the drug and treatment with corticosteroids. Given that there was no prior history of hemolysis, even during treatment with ipilimumab, we hypothesize that anti-PD-1 therapy disrupted peripheral tolerance, unmasking an underlying autoimmune predisposition. PMID:26795275

  3. Mesenchymal stem cells as delivery vectors for anti-tumor therapy

    PubMed Central

    Li, Zhenzhen; Fan, Dongmei

    2015-01-01

    Recent studies have demonstrated mesenchymal stem cells (MSCs) are able to migrate specifically to tumors and their metastatic sites when administered intravenously. This characteristic tumor tropism has opened up an emerging field to utilize MSCs as vectors to deliver anti-cancer agents for targeted therapies. Genetically engineered MSCs can specifically migrate to various tumors and locally secrete therapeutic proteins, such as interferon β (IFN-β) and IFN-γ, interleukin 12 and 24, tumor necrosis factor-related apoptosis inducing ligand (TRAIL) or suicide gene/enzyme prodrug. In addition, MSCs have also been engineered to deliver oncolytic viruses and drug-loaded nanoparticles. Here, we present the characteristics of MSCs, the current progress on MSC mediated anti-cancer agents delivery systems and the interaction between MSCs and tumors.

  4. Manipulating TLR Signaling Increases the Anti-tumor T Cell Response Induced by Viral Cancer Therapies.

    PubMed

    Rojas, Juan J; Sampath, Padma; Bonilla, Braulio; Ashley, Alexandra; Hou, Weizhou; Byrd, Daniel; Thorne, Steve H

    2016-04-12

    The immune response plays a key role in enhancing the therapeutic activity of oncolytic virotherapies. However, to date, investigators have relied on inherent interactions between the virus and the immune system, often coupled to the expression of a single cytokine transgene. Recently, the importance of TLR activation in mediating adaptive immunity has been demonstrated. We therefore sought to influence the type and level of immune response raised after oncolytic vaccinia therapy through manipulation of TLR signaling. Vaccinia naturally activates TLR2, associated with an antibody response, whereas a CTL response is associated with TLR3-TRIF-signaling pathways. We manipulated TLR signaling by vaccinia through deglycosylation of the viral particle to block TLR2 activation and expression of a TRIF transgene. The resulting vector displayed greatly reduced production of anti-viral neutralizing antibody as well as an increased anti-tumor CTL response. Delivery in both naive and pre-treated mice was enhanced and immunotherapeutic activity dramatically improved. PMID:27050526

  5. Intracellular Redox State as Target for Anti-Influenza Therapy: Are Antioxidants Always Effective?

    PubMed Central

    Sgarbanti, Rossella; Amatore, Donatella; Celestino, Ignacio; Marcocci, Maria Elena; Fraternale, Alessandra; Ciriolo, Maria Rosa; Magnani, Mauro; Saladino, Raffaele; Garaci, Enrico; Palamara, Anna Teresa; Nencioni, Lucia

    2014-01-01

    Influenza virus infections represent a big issue for public health since effective treatments are still lacking. In particular, the emergence of strains resistant to drugs limits the effectiveness of anti-influenza agents. For this reason, many efforts have been dedicated to the identification of new therapeutic strategies aimed at targeting the virus-host cell interactions. Oxidative stress is a characteristic of some viral infections including influenza. Because antioxidants defend cells from damage caused by reactive oxygen species induced by different stimuli including pathogens, they represent interesting molecules to fight infectious diseases. However, most of the available studies have found that these would-be panaceas could actually exacerbate the diseases they claim to prevent, and have thus revealed "the dark side" of these molecules. This review article discusses the latest opportunities and drawbacks of the antioxidants used in anti-influenza therapy and new perspectives. PMID:25478883

  6. Ophthalmic manifestations of HIV in the highly active anti-retroviral therapy era.

    PubMed

    Mowatt, L

    2013-01-01

    HIV-related eye disease can be classified as retinal HIV microangiopathy, opportunistic infections, neuro-ophthalmic manifestations and unusual malignancies. There is a 52-100% lifetime accumulative risk of HIV patients developing eye problems. Seventy-seven per cent of patients with ocular manifestations of HIV had CD4 counts < 200 cells/μL. Cytomegalovirus (CMV) is the most prevalent opportunistic infection, however, Africa has a low incidence of this, and more commonly squamous cell carcinoma, compared to the western hemisphere. Due to highly active antiretroviral therapy (HAART), the anti-CMV therapy may be discontinued if the CD4+ T cell count is > 100 cells/μL for a minimum of three months. Despite HAART, patients with a CD4 count < 50 cells/μL have a similar risk of developing CMV retinitis as compared to the pre-HAART era. Opportunistic infections include CMV, herpetic retinopathy (progressive outer retinal necrosis - PORN), less commonly toxoplasmosis, pneumocystis and cryptococcus. Malignancies associated with HIV include Kaposi's sarcoma and conjunctival squamous cell carcinoma. Cranial nerve palsies, optic disc swelling and atrophy are characteristic neuro-ophthalmic features. They usually occur secondary to meningitis/encephalitis (from cryptococcus and tuberculosis). With the advent of HAART, new complications have developed in CMV retinitis: immune recovery uveitis (IRU) and cystoid macula oedema (CMO). Immune recovery uveitis occurs in 71% of patients if HAART is started before the induction of the anti-CMV treatment. However, this is reduced to 31% if HAART is started after the induction treatment. Molluscum contagiosum and Kaposi's sarcoma can spontaneously resolve on HAART. Highly active anti-retroviral therapy has reduced the frequencies of opportunistic infections and improved the remission duration in HIV patients. PMID:24756590

  7. Managed care aspects of psoriasis and psoriatic arthritis.

    PubMed

    Evans, Colby

    2016-06-01

    The chronic and systemic nature of psoriasis has a significant impact on direct costs, indirect costs, and patient quality of life. Psoriasis is associated with comorbid conditions that add to the burden of the disease, especially in moderate to severe disease. The total estimated annual healthcare burden of psoriasis may be as high as $35.2 billion, with $12.2 billion in direct costs and $23 billion in indirect costs (attributed to reduced health-related quality of life and lost productivity). These costs vary based on the severity of the disease; pharmacy costs account for the majority of the burden, especially in severe disease. Biologic therapies are largely responsible for the pharmacy costs. Approval of biosimilar products in the near future may ease some of this burden for payers and patients, although new agents have also been recently approved, with more in the pipeline. The healthcare costs of psoriasis management substantially increase with comorbid conditions, such as heart disease, hyperlipidemia, hypertension, diabetes, and lung disease. These comorbidities also include psychiatric conditions, such as social stigmatization, depression, and suicide. The overall costs associated with comorbidities are estimated to be an additional $22,713 per patient per year. Appropriate treatment selection and timing may curtail the progression of psoriasis, and, as a result, can decrease the economic burden. As treatment options vary based on comorbidities, long-term remission goals, and medication costs, conducting a comprehensive patient assessment is imperative. Drug utilization reviews steered by specialty pharmacists may help reduce costs and improve outcomes by providing treatment monitoring and patient education. PMID:27356195

  8. Spontaneous hematoma in the setting of dual anti-platelet therapy with ticagrelor: A case report

    PubMed Central

    FENG, CHUNGUANG; WANG, LINGUANG; WANG, LULU

    2016-01-01

    A 69-year-old male patient was admitted to hospital because a lump was discovered, accompanied with pain lasting 5 h under his right scapula. Two months earlier, he had undergone a double-stent insertion operation due to lesions on the end of the left main coronary artery, the opening of left circumflex artery, and the opening of the anterior descending branch. After the operation, he was administered with dual anti-platelet therapy (DAPT) with aspirin and ticagrelor and was diagnosed with hematoma under his right scapula through ultrasonic inspection. It was established that no other factor, except DAPT, was responsible for his spontaneous hematoma. PMID:27347115

  9. Adenosine: an endogenous mediator in the pathogenesis of psoriasis*

    PubMed Central

    Festugato, Moira

    2015-01-01

    It is known that inflammatory and immune responses protect us from the invasion of micro-organisms and eliminate "wastes" from the injured sites, but they may also be responsible for significant tissue damage. Adenosine, as a purine nucleoside, which is produced in inflamed or injured sites, fulfills its role in limiting tissue damage. Although, it may have a pleiotropic effect, which signals it with a proinflammatory state in certain situations, it can be considered a potent anti-inflammatory mediator. The effects of adenosine, which acts through its receptors on T cell, on mast cell and macrophages, on endothelial cells, on neutrophils and dendritic cells, as they indicate TNF-alpha and cytokines, show that this mediator has a central role in the pathogenesis of psoriasis. The way it acts in psoriasis will be reviewed in this study. PMID:26734868

  10. Early blood pressure, anti-hypotensive therapy and outcomes at 18 to 22 month corrected age in extremely preterm infants

    PubMed Central

    Batton, Beau; Li, Lei; Newman, Nancy S.; Das, Abhik; Watterberg, Kristi L.; Yoder, Bradley A.; Faix, Roger G.; Laughon, Matthew M.; Stoll, Barbara J.; Higgins, Rosemary D.; Walsh, Michele C.

    2016-01-01

    Objective Investigate relationships between early blood pressure (BP) changes, receipt of anti-hypotensive therapy, and 18 – 22 month corrected age (CA) outcomes for extremely preterm infants. Design Prospective observational study of infants 230/7 – 266/7 weeks gestational age (GA). Hourly BP values and anti-hypotensive therapy exposure in the first 24 hours were recorded. Four groups were defined: infants who did or did not receive anti-hypotensive therapy in whom BP did or did not rise at the expected rate (defined as an increase in the mean arterial BP of ≥5 mmHg/day). Random-intercept logistic modeling controlling for center clustering, GA, and illness severity was used to investigate the relationship between BP, anti-hypotensive therapies, and infant outcomes. Setting Sixteen academic centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Main Outcome Measures Death or neurodevelopmental impairment / developmental delay (NIDD) at 18 – 22 months CA. Results Of 367 infants, 203 (55%) received an anti-hypotensive therapy, 272 (74%) survived to discharge, and 331 (90%) had a known outcome at 18 – 22 months CA. With logistic regression, there was an increased risk of death/NIDD with anti-hypotensive therapy versus no treatment (odds ratio: 1.836, 95% confidence interval: 1.092 – 3.086), but not NIDD alone (odds ratio: 1.53, 95% confidence interval: 0.708 – 3.307). Conclusion Independent of early BP changes, anti-hypotensive therapy exposure was associated with an increased risk of death/NIDD at 18 to 22 months CA when controlling for risk factors known to affect survival and neurodevelopment. PMID:26567120

  11. New developments in small molecular compounds for anti-hepatitis C virus (HCV) therapy*

    PubMed Central

    Tong, Jing; Wang, You-wei; Lu, Yuan-an

    2012-01-01

    Infection with hepatitis C virus (HCV) affects approximately 170 million people worldwide. However, no vaccine or immunoglobulin is currently available for the prevention of HCV infection. The standard of care (SOC) involving pegylated interferon-α (PEG-IFN α) plus ribavirin (RBV) for 48 weeks results in a sustained virologic response in less than 50% of patients with chronic hepatitis C genotype 1, the most prevalent type of HCV in North America and Europe. Recently, reliable in vitro culture systems have been developed for accelerating antiviral therapy research, and many new specifically targeted antiviral therapies for hepatitis C (STAT-C) and treatment strategies are being evaluated in clinical trials. These new antiviral agents are expected to improve present treatment significantly and may potentially shorten treatment duration. The aim of this review is to summarize the current developments in new anti-HCV drugs. PMID:22205621

  12. iPSCs-based anti-aging therapies: Recent discoveries and future challenges.

    PubMed

    Pareja-Galeano, Helios; Sanchis-Gomar, Fabián; Pérez, Laura M; Emanuele, Enzo; Lucia, Alejandro; Gálvez, Beatriz G; Gallardo, María Esther

    2016-05-01

    The main biological hallmarks of the aging process include stem cell exhaustion and cellular senescence. Consequently, research efforts to treat age-related diseases as well as anti-aging therapies in general have recently focused on potential 'reprogramming' regenerative therapies. These new approaches are based on induced pluripotent stem cells (iPSCs), including potential in vivo reprogramming for tissue repair. Another possibility is targeting pathways of cellular senescence, e.g., through modulation of p16INK4a signaling and especially inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Here, we reviewed and discussed these recent developments together with their possible usefulness for future treatments against sarcopenia, a major age-related condition. PMID:26921478

  13. Vessel Architectural Imaging Identifies Cancer Patient Responders to Anti-angiogenic Therapy

    PubMed Central

    Emblem, Kyrre E.; Mouridsen, Kim; Bjornerud, Atle; Farrar, Christian T.; Jennings, Dominique; Borra, Ronald J. H.; Wen, Patrick Y.; Ivy, Percy; Batchelor, Tracy T.; Rosen, Bruce R.; Jain, Rakesh K.; Sorensen, A. Gregory

    2013-01-01

    Measurement of vessel caliber by Magnetic Resonance Imaging (MRI) is a valuable technique for in vivo monitoring of hemodynamic status and vascular development, especially in the brain. Here, we introduce a new paradigm in MRI coined as Vessel Architectural Imaging (VAI) that exploits an intriguing and overlooked temporal shift in the MR signal forming the basis for vessel caliber estimation and show how this phenomenon can reveal new information on vessel type and function not assessed by any other non-invasive imaging technique. We also show how this biomarker can provide novel biological insights into the treatment of cancer patients. As an example, we demonstrate using VAI that anti-angiogenic therapy can improve microcirculation and oxygen saturation levels and reduce vessel calibers in patients with recurrent glioblastomas, and more crucially, that patients with these responses have prolonged survival. Thus, VAI has the potential to identify patients who would benefit from therapies. PMID:23955713

  14. Large Vessel Vasculitis Occurring in Rheumatoid Arthritis Patient under Anti-TNF Therapy

    PubMed Central

    Cestelli, Valentina; Spinella, Amelia; Campomori, Federica; Esposito, Carmela; Ciaffi, Sara; Sandri, Gilda; Ferri, Clodoveo

    2014-01-01

    Vasculitis is a heterogeneous group of disorders characterized by the presence of necrotic inflammatory phenomena and destruction of blood vessels. Vasculitis is classified as primary (idiopathic) or secondary to infections, connective tissue diseases and drugs but can also be considered as a paraneoplastic phenomenon. Evidence shows that the increasing use of biological agents results in a growing number of reports of autoimmune diseases induced by these therapies. An inflammatory articular chronic disease such as rheumatoid arthritis may be complicated by extra-articular manifestations, such as cutaneous or systemic vasculitis. Herewith, we describe the case of a great vessels arteritis in a patient affected by rheumatoid arthritis in therapy with an anti-TNF agent (etanercept). PMID:25544845

  15. Anti-CCR7 therapy exerts a potent anti-tumor activity in a xenograft model of human mantle cell lymphoma

    PubMed Central

    2013-01-01

    Background The chemokine receptor CCR7 mediates lymphoid dissemination of many cancers, including lymphomas and epithelial carcinomas, thus representing an attractive therapeutic target. Previous results have highlighted the potential of the anti-CCR7 monoclonal antibodies to inhibit migration in transwell assays. The present study aimed to evaluate the in vivo therapeutic efficacy of an anti-CCR7 antibody in a xenografted human mantle cell lymphoma model. Methods NOD/SCID mice were either subcutaneously or intravenously inoculated with Granta-519 cells, a human cell line derived from a leukemic mantle cell lymphoma. The anti-CCR7 mAb treatment (3 × 200 μg) was started on day 2 or 7 to target lymphoma cells in either a peri-implantation or a post-implantation stage, respectively. Results The anti-CCR7 therapy significantly delayed the tumor appearance and also reduced the volumes of tumors in the subcutaneous model. Moreover, an increased number of apoptotic tumor cells was detected in mice treated with the anti-CCR7 mAb compared to the untreated animals. In addition, significantly reduced number of Granta-519 cells migrated from subcutaneous tumors to distant lymphoid organs, such as bone marrow and spleen in the anti-CCR7 treated mice. In the intravenous models, the anti-CCR7 mAb drastically increased survival of the mice. Accordingly, dissemination and infiltration of tumor cells in lymphoid and non-lymphoid organs, including lungs and central nervous system, was almost abrogated. Conclusions The anti-CCR7 mAb exerts a potent anti-tumor activity and might represent an interesting therapeutic alternative to conventional therapies. PMID:24305507

  16. A multi-centred open trial of “Dr Michaels®” (also branded as Soratinex®) topical product family in psoriasis.

    PubMed

    Wollina, U; Hercogovấ, J; Fioranelli, M; Gianfaldoni, S; Chokoeva, A A; Tchernev, G; Tirant, M; Novotny, F; Roccia, M G; Maximov, G K; França, K; Lotti, T

    2016-01-01

    Psoriasis is a chronic, recurring skin disease affecting 2-4% of the population. Genetic predisposition and precipitating factors play a role in its etiology. The disease can occur in any age or gender group. The most frequently affected areas of the body include scalp, extensor surfaces of the extremities, skin folds and nails. While a number of therapies exist for the treatment of psoriasis with a total resolution of the skin, achieving remission in a high percentage of sufferers, a treatment that results in the maintenance of remission and is free of side effects is still a desirable goal. The aim of the study was to investigate the efficacy and tolerability of Dr Michaels® (Soratinex®) topical product family in psoriasis, in terms of decreasing parakeratosis, inflammation, infiltration and involved area. Seven-hundred-and-twenty-two subjects, mean age 42.3 years (range: 18-68 years) with mild to moderately severe psoriasis, with no other current anti-psoriatic therapy, consisting of 382 males and 340 females, above 18 years of age were included and the observations were subjected to statistical analysis. Triphasic application of Dr Michaels® (Soratinex®) products was employed for 8 weeks, using Cleansing Gel, Scalp and Body Ointment and Skin Conditioner. The treatment proved to be ineffective for 22 patients (3.1%) out of 722. 84 patients (11.6%) had moderate improvement with 26-50% of cleared skin lesions; 102 patients (14.1%) had good improvement with 51-75% of cleared skin lesions; 484 patients (67.0%) experienced outstanding improvement with 76-100% of the cleared skin lesions, with 52% of them achieving total resolution. Twelve patients worsened and discontinued treatment; 18 patients discontinued because of non-compliance; 33 patients developed folliculitis as a side effect. Based on the results of this study, the Dr Michaels® (Soratinex®) product family can be successfully applied in mild to moderately severe psoriasis when considering the

  17. Steroids block the anti-inflammatory effects of low level laser therapy

    NASA Astrophysics Data System (ADS)

    Lopes-Martins, Rodrigo Alvaro B.; Albertini, Regiane; Lopes-Martins, Patricia Sardinha L.; Iversen, Vegard V.; Bjordal, Jan M.

    2006-02-01

    Objective: Concomitant use of multiple therapies is common in musculoskeletal and airway disorders. Low level laser therapy (LLLT) is considered a promising therapy in arthritis, tendinopathies and rhinitis. We designed two animal studies to assess if the expected anti-inflammatory effect LLLT could be affected by resection of the adrenal gland or concomitant use of the cortisol antagonist mifepristone. Methods: Two studies were performed, with 40 male Wistar rats and with 40 Balb C male mice respectively.. In both studies, four groups received carrageenan and one control group received saline. At 1, 2, and 3 hours after injections, LLLT irradiation was performed with a dose of 7.5 J/cm2. In the rat study, two of the carrageenan groups had the adrenal gland dissected. In the mice study, two of the carrageenan-injected groups were in addition pre-treated with orally administered mifepristone. Results: In the rat paw study, LLLT reduced edema significantly compared to the carrageenan only group (1.5 vs 0.9 ml, p< 0.05), but LLLT failed to inhibit edema formation in the group which had the adrenal gland resected. In carrageenan-induced pleurisy, LLLT significantly reduced the number of leukocyte cells ( p<0.0001, Mean 34.5 [95%CI: 32.8 - 36.2] versus 87.7 [95%CI: 81.0 - 94.4]), and that the effect of LLLT could be totally blocked by adding the cortisol antagonist mifepristone ( p<0.0001, Mean 34.5 [95%CI: 32.1 - 36.9] versus 82.9 [95%CI: 70.5 - 95.3]). Conclusion: Steroid therapy should not be used concomitantly with LLLT, as the anti-inflammatory effect of LLLT is lost if cortisol receptors are downregulated.

  18. Characterization of N-acetylcysteine and ambroxol in anti-oxidant therapy.

    PubMed

    Gillissen, A; Nowak, D

    1998-04-01

    pulmonary diseases, and it discusses the feasibility of anti-oxidant augmentation therapy to the lung by using NAC or ambroxol. PMID:9659525

  19. Curcumin shows excellent therapeutic effect on psoriasis in mouse model.

    PubMed

    Kang, Di; Li, Bowen; Luo, Lei; Jiang, Wenbing; Lu, Qiumin; Rong, Mingqing; Lai, Ren

    2016-04-01

    Curcumin is an active herbal ingredient possessing surprisingly wide range of beneficial properties, including anti-inflammatory, antioxidant, chemopreventive and chemotherapeutic activity. Recently, it has been reported to exhibit inhibitory activity on potassium channel subtype Kv1.3. As Kv1.3 channels are mainly expressed in T cells and play a key role in psoriasis, the effects of curcumin were investigated on inflammatory factors secretion in T cells and psoriasis developed in keratin (K) 14-vascular endothelial growth factor (VEGF) transgenic mouse model. Results showed that, 10 μM of curcumin significantly inhibited secretion of inflammatory factors including interleukin (IL)-17,IL-22, IFN-γ, IL-2, IL-8 and TNF-α in T cells by 30-60% in vitro. Notably, more than 50% of T cells proliferation was inhibited by application of 100 μM curcumin. Compared with severe psoriatic symptoms observed in the negative control mice, all psoriasis indexes including ear redness, weight, thickness and lymph node weight were significantly improved by oral application of curcumin in treatment mouse group. Histological examination indicated that curcumin had anti-inflammatory function in the experimental animals. More than 50% level of inflammatory factors including TNF-α, IFN-γ, IL-2, IL-12, IL-22 and IL-23 in mouse serum was decreased by curcumin treatment as well as cyclosporine. Compared with renal fibrosis observed in the mouse group treated by cyclosporine, no obvious side effect in mouse kidney was found after treated by curcumin. Taken together, curcumin, with high efficacy and safety, has a great potential to treat psoriasis. PMID:26826458

  20. Anti-rotavirus effects by combination therapy of stevioside and Sophora flavescens extract.

    PubMed

    Alfajaro, Mia Madel; Rho, Mun-Chual; Kim, Hyun-Jeong; Park, Jun-Gyu; Kim, Deok-Song; Hosmillo, Myra; Son, Kyu-Yeol; Lee, Ju-Hwan; Park, Sang-Ik; Kang, Mun-Il; Ryu, Young Bae; Park, Ki Hun; Oh, Hyun-Mee; Lee, Seung Woong; Park, Su-Jin; Lee, Woo Song; Cho, Kyoung-Oh

    2014-06-01

    Anti-rotaviral activities of Sophora flavescens extract (SFE) and stevioside (SV) from Stevia rebaudiana Bertoni either singly or in various combinations were examined in vitro and in vivo using a porcine rotavirus G5[P7] strain. Combination of SFE and SV inhibited in vitro virus replication more efficiently than each single treatment. In the piglet model, SV had no effect on rotavirus enteritis, whereas SFE improved but did not completely cure rotaviral enteritis. Interestingly, combination therapy of SFE and SV alleviated diarrhea, and markedly improved small intestinal lesion score and fecal virus shedding. Acute toxicity tests including the piglet lethal dose 50, and body weight, organ weight and pathological changes for the combination therapy did not show any adverse effect on the piglets. These preliminary data suggest that the combination therapy of SV and SFE is a potential curative medication for rotaviral diarrhea in pigs. Determination of the efficacy of this combination therapy in other species including humans needs to be addressed in the future. PMID:24704033

  1. Nimotuzumab increases the anti-tumor effect of photodynamic therapy in an oral tumor model.

    PubMed

    Bhuvaneswari, Ramaswamy; Ng, Qin Feng; Thong, Patricia S P; Soo, Khee-Chee

    2015-05-30

    Oral squamous cell carcinoma (OSCC) represents 90% of all oral cancers and is characterized with poor prognosis and low survival rate. Epidermal growth factor receptor (EGFR) is highly expressed in oral cancer and is a target for cancer therapy and prevention. In this present work, we evaluate the efficacy of photodynamic therapy (PDT) in combination with an EGFR inhibitor, nimotuzumab in oral cancer cell lines and OSCC xenograft tumor model. PDT is a promising and minimally invasive treatment modality that involves the interaction of a photosensitizer, molecular oxygen and light to destroy tumors. We demonstrated that EGFR inhibitors nimotuzumab and cetuximab exhibits anti-angiogenic properties by inhibiting the migration and invasion of oral cancer cell lines and human endothelial cells. The EGFR inhibitors also significantly reduced tube formation of endothelial cells. Chlorin e6-PDT in combination with nimotuzumab and cetuximab reduced cell proliferation in different oral cancer and endothelial cells. Furthermore, our in vivo studies showed that the combination therapy of PDT and nimotuzumab synergistically delayed tumor growth when compared with control and PDT treated tumors. Downregulation of EGFR, Ki-67 and CD31 was observed in the tumors treated with combination therapy. Analysis of the liver and kidney function markers showed no treatment related toxicity. In conclusion, PDT outcome of oral cancer can be improved when combined with EGFR inhibitor nimotuzumab. PMID:25918252

  2. Metastatic renal cell carcinoma imaging evaluation in the era of anti-angiogenic therapies.

    PubMed

    Sirous, Reza; Henegan, John C; Zhang, Xu; Howard, Candace M; Souza, Frederico; Smith, Andrew D

    2016-06-01

    During the last decade, the arsenal of anti-angiogenic (AAG) agents used to treat metastatic renal cell carcinoma (RCC) has grown and revolutionized the treatment of metastatic RCC, leading to improved overall survival compared to conventional chemotherapy and traditional immunotherapy agents. AAG agents include inhibitors of vascular endothelial growth factor receptor signaling pathways and mammalian target of rapamycin inhibitors. Both of these classes of targeted agents are considered cytostatic rather than cytotoxic, inducing tumor stabilization rather than marked tumor shrinkage. As a result, decreases in tumor size alone are often minimal and/or occur late in the course of successful AAG therapy, while tumor devascularization is a distinct feature of AAG therapy. In successful AAG therapy, tumor devascularization manifests on computed tomography images as a composite of a decrease in tumor size, a decrease in tumor attenuation, and the development of tumor necrosis. In this article, we review Response Evaluation Criteria in Solid Tumors (RECIST)-the current standard of care for tumor treatment response assessment which is based merely on changes in tumor length-and its assessment of metastatic RCC tumor response in the era of AAG therapies. We then review the features of an ideal tumor imaging biomarker for predicting metastatic RCC response to a particular AAG agent and serving as a longitudinal tumor response assessment tool. Finally, a discussion of the more recently proposed imaging response criteria and new imaging trends in metastatic RCC response assessment will be reviewed. PMID:27193601

  3. Nimotuzumab increases the anti-tumor effect of photodynamic therapy in an oral tumor model

    PubMed Central

    Bhuvaneswari, Ramaswamy; Ng, Qin Feng; Thong, Patricia S.P.; Soo, Khee-Chee

    2015-01-01

    Oral squamous cell carcinoma (OSCC) represents 90% of all oral cancers and is characterized with poor prognosis and low survival rate. Epidermal growth factor receptor (EGFR) is highly expressed in oral cancer and is a target for cancer therapy and prevention. In this present work, we evaluate the efficacy of photodynamic therapy (PDT) in combination with an EGFR inhibitor, nimotuzumab in oral cancer cell lines and OSCC xenograft tumor model. PDT is a promising and minimally invasive treatment modality that involves the interaction of a photosensitizer, molecular oxygen and light to destroy tumors. We demonstrated that EGFR inhibitors nimotuzumab and cetuximab exhibits anti-angiogenic properties by inhibiting the migration and invasion of oral cancer cell lines and human endothelial cells. The EGFR inhibitors also significantly reduced tube formation of endothelial cells. Chlorin e6-PDT in combination with nimotuzumab and cetuximab reduced cell proliferation in different oral cancer and endothelial cells. Furthermore, our in vivo studies showed that the combination therapy of PDT and nimotuzumab synergistically delayed tumor growth when compared with control and PDT treated tumors. Downregulation of EGFR, Ki-67 and CD31 was observed in the tumors treated with combination therapy. Analysis of the liver and kidney function markers showed no treatment related toxicity. In conclusion, PDT outcome of oral cancer can be improved when combined with EGFR inhibitor nimotuzumab. PMID:25918252

  4. Biological therapy for dermatological manifestations of inflammatory bowel disease

    PubMed Central

    Zippi, Maddalena; Pica, Roberta; De Nitto, Daniela; Paoluzi, Paolo

    2013-01-01

    Ulcerative colitis and Crohn’s disease are the two forms of inflammatory bowel disease (IBD). The advent of biological drugs has significantly changed the management of these conditions. Skin manifestations are not uncommon in IBD. Among the reactive lesions (immune-mediated extraintestinal manifestations), erythema nodosum (EN) and pyoderma gangrenosum (PG) are the two major cutaneous ills associated with IBD, while psoriasis is the dermatological comorbidity disease observed more often. In particular, in the last few years, anti-tumor necrosis factor (TNF)-α agents have been successfully used to treat psoriasis, especially these kinds of lesions that may occur during the treatment with biological therapies. The entity of the paradoxical manifestations has been relatively under reported as most lesions are limited and a causal relationship with the treatment is often poorly understood. The reason for this apparent side-effect of the therapy still remains unclear. Although side effects may occur, their clinical benefits are undoubted. This article reviews the therapeutic effects of the two most widely used anti-TNF-α molecules, infliximab (a fusion protein dimer of the human TNF-α receptor) and adalimumab (a fully human monoclonal antibody to TNF-α), for the treatment of the major cutaneous manifestations associated with IBD (EN, PG and psoriasis). PMID:24303470

  5. Recent advances in understanding psoriasis

    PubMed Central

    Eberle, Franziska C.; Brück, Jürgen; Holstein, Julia; Hirahara, Kiyoshi; Ghoreschi, Kamran

    2016-01-01

    T helper (Th) cells producing interleukin (IL)-17, IL-22, and tumor necrosis factor (TNF) form the key T cell population driving psoriasis pathogenesis. They orchestrate the inflammation in the skin that results in the proliferation of keratinocytes and endothelial cells. Besides Th17 cells, other immune cells that are capable of producing IL-17-associated cytokines participate in psoriatic inflammation. Recent advances in psoriasis research improved our understanding of the cellular and molecular players that are involved in Th17 pathology and inflammatory pathways in the skin. The inflammation-driving actions of TNF in psoriasis are already well known and antibodies against TNF are successful in the treatment of Th17-mediated psoriatic skin inflammation. A further key cytokine with potent IL-17-/IL-22-promoting properties is IL-23. Therapeutics directly neutralizing IL-23 or IL-17 itself are now extending the therapeutic spectrum of antipsoriatic agents and further developments are on the way. The enormous progress in psoriasis research allows us to control this Th17-mediated inflammatory skin disease in many patients. PMID:27158469

  6. Nail Psoriasis: The Journey So Far

    PubMed Central

    Dogra, Alka; Arora, Amanjot Kaur

    2014-01-01

    Nail involvement is an extremely common feature of psoriasis and affects approximately 10-78% of psoriasis patients with 5-10% of patients having isolated nail psoriasis. However, it is often an overlooked feature in the management of nail psoriasis, despite the significant burden it places on the patients as a result of functional impairment of manual dexterity, pain, and psychological stress. Affected nail plates often thicken and crumble, and because they are very visible, patients tend to avoid normal day-to-day activities and social interactions. Importantly, 70-80% of patients with psoriatic arthritis have nail psoriasis. In this overview, we review the clinical manifestations of psoriasis affecting the nails, the common differential diagnosis of nail psoriasis, Nail Psoriasis Severity Index and the various diagnostic aids for diagnosing nail psoriasis especially, the cases with isolated nail involvement. We have also discussed the available treatment options, including the topical, physical, systemic, and biological modalities, in great detail in order to equip the present day dermatologist in dealing with a big clinical challenge, that is, management of nail psoriasis. PMID:25071247

  7. Psoriasis, guttate on the arms and chest (image)

    MedlinePlus

    ... guttate (drop-shaped) psoriasis on the arms and chest. Guttate psoriasis is a rare form of psoriasis. ... streptococcal infection, appears rapidly and affects the face, chest, and nearest limbs. The patches are small and ...

  8. Targeted Therapy of Cancer Using Photodynamic Therapy in Combination with Multi-faceted Anti-Tumor Modalities

    PubMed Central

    Olivo, Malini; Bhuvaneswari, Ramaswamy; Lucky, Sasidharan Swarnalatha; Dendukuri, Nagamani; Thong, Patricia Soo-Ping

    2010-01-01

    Photodynamic therapy (PDT) has emerged as one of the important therapeutic options in the management of cancer and other diseases. PDT involves a tumor-localized photosensitizer (PS), which when appropriately illuminated by visible light converts oxygen into cytotoxic reactive oxygen species (ROS), that attack key structural entities within the targeted cells, ultimately resulting in necrosis or apoptosis. Though PDT is a selective modality, it can be further enhanced by combining other targeted therapeutic strategies that include the use of synthetic peptides and nanoparticles for selective delivery of photosensitizers. Another potentially promising strategy is the application of targeted therapeutics that exploit a myriad of critical pathways involved in tumorigenesis and metastasis. Vascular disrupting agents that eradicate tumor vasculature during PDT and anti-angiogenic agents that targets specific molecular pathways and prevent the formation of new blood vessels are novel therapeutic approaches that have been shown to improve treatment outcome. In addition to the well-documented mechanisms of direct cell killing and damage to the tumor vasculature, PDT can also activate the body’s immune response against tumors. Numerous pre-clinical studies and clinical observations have demonstrated the immuno-stimulatory capability of PDT. Herein, we aim to integrate the most important findings with regard to the combination of PDT and other novel targeted therapy approaches, detailing its potential in cancer photomedicine.

  9. [Tear in retinal pigment epithelium under anti-VEGF therapy for exudative age-related macular degeneration : function recovery under intensive therapy].

    PubMed

    Bartels, S; Barrelmann, A; Book, B; Heimes, B; Gutfleisch, M; Spital, G; Pauleikhoff, D; Lommatzsch, A

    2014-05-01

    This article reports the case of a 72-year-old woman with pigment epithelial detachment with occult choroidal neovascularization (CNV) in exudative age-related macular degeneration (AMD) which developed under anti-vascular endothelial growth factor (VEGF) therapy of a tear in the retinal pigment epithelium (RPE). In the area of free RPE autofluorescence was completely absent and the microperimetry in this area showed an absolute scotoma. The visual acuity was 0.1. After continuation of anti-VEGF therapy because of persistent subretinal and intraretinal fluid over 3 years an increased autofluorescence was observed and the microperimetry showed an increase in central retinal sensitivity. The central visual acuity improved to 0.5 and in this area a whitish subretinal tissue formed morphologically. In the spectral domain optical coherence tomography (SD-OCT) image this structure was hyperreflective which might suggest a certain regeneration process of the RPE under anti-VEGF-therapy. PMID:24046170

  10. German evidence-based guidelines for the treatment of Psoriasis vulgaris (short version)

    PubMed Central

    Kopp, I.; Augustin, M.; Banditt, K. B.; Boehncke, W. H.; Follmann, M.; Friedrich, M.; Huber, M.; Kahl, C.; Klaus, J.; Koza, J.; Kreiselmaier, I.; Mohr, J.; Mrowietz, U.; Ockenfels, H. M.; Orzechowski, H. D.; Prinz, J.; Reich, K.; Rosenbach, T.; Rosumeck, S.; Schlaeger, M.; Schmid-Ott, G.; Sebastian, M.; Streit, V.; Weberschock, T.; Rzany, B.

    2007-01-01

    Psoriasis vulgaris is a common and chronic inflammatory skin disease which has the potential to significantly reduce the quality of life in severely affected patients. The incidence of psoriasis in Western industrialized countries ranges from 1.5 to 2%. Despite the large variety of treatment options available, patient surveys have revealed insufficient satisfaction with the efficacy of available treatments and a high rate of medication non-compliance. To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis. The guidelines focus on induction therapy in cases of mild, moderate, and severe plaque-type psoriasis in adults. The short version of the guidelines reported here consist of a series of therapeutic recommendations that are based on a systematic literature search and subsequent discussion with experts in the field; they have been approved by a team of dermatology experts. In addition to the therapeutic recommendations provided in this short version, the full version of the guidelines includes information on contraindications, adverse events, drug interactions, practicality, and costs as well as detailed information on how best to apply the treatments described (for full version, please see Nast et al., JDDG, Suppl 2:S1–S126, 2006; or http://www.psoriasis-leitlinie.de). PMID:17497162

  11. Safety and efficacy of calcium folinate in psoriasis: an observational study.

    PubMed

    Carlesimo, M; Mari, E; Arcese, A; De Angelis, F; Palese, E; Abruzzese, C; De Marco, G; Cattaruzza, M S; Camplone, G

    2010-01-01

    An association between psoriasis and cardiovascular diseases has been reported, and treatment of this condition is often considered difficult because the conventional systemic therapies often show several side effects. To assess the efficacy and tolerability of a new drug, folinate calcium, to treat psoriasis, a total of 58 patients affected by active psoriasis were enrolled in a variable period study. These patients had clinically stable, plaque psoriasis involving greater than or equal 6% body surface area. Thirty of these patients were treated with folinate calcium therapy, 15 mg orally once daily, for a variable period based on each patients clinical response. The comparison was made with 28 psoriatic patients treated with conventional systemic therapies (cyclosporine, acitretin, etanercept, efalizumab, infliximab, adalimumab). A clinical improvement was observed in both group, but in the first one we did not observe any side effects, whereas some important side effects were observed in the second. These preliminary results support the effectiveness and tolerability of folinate calcium treatment in psoriasis. PMID:20646362

  12. Toward Repurposing Metformin as a Precision Anti-Cancer Therapy Using Structural Systems Pharmacology

    PubMed Central

    Hart, Thomas; Dider, Shihab; Han, Weiwei; Xu, Hua; Zhao, Zhongming; Xie, Lei

    2016-01-01

    Metformin, a drug prescribed to treat type-2 diabetes, exhibits anti-cancer effects in a portion of patients, but the direct molecular and genetic interactions leading to this pleiotropic effect have not yet been fully explored. To repurpose metformin as a precision anti-cancer therapy, we have developed a novel structural systems pharmacology approach to elucidate metformin’s molecular basis and genetic biomarkers of action. We integrated structural proteome-scale drug target identification with network biology analysis by combining structural genomic, functional genomic, and interactomic data. Through searching the human structural proteome, we identified twenty putative metformin binding targets and their interaction models. We experimentally verified the interactions between metformin and our top-ranked kinase targets. Notably, kinases, particularly SGK1 and EGFR were identified as key molecular targets of metformin. Subsequently, we linked these putative binding targets to genes that do not directly bind to metformin but whose expressions are altered by metformin through protein-protein interactions, and identified network biomarkers of phenotypic response of metformin. The molecular targets and the key nodes in genetic networks are largely consistent with the existing experimental evidence. Their interactions can be affected by the observed cancer mutations. This study will shed new light into repurposing metformin for safe, effective, personalized therapies. PMID:26841718

  13. Toward Repurposing Metformin as a Precision Anti-Cancer Therapy Using Structural Systems Pharmacology.

    PubMed

    Hart, Thomas; Dider, Shihab; Han, Weiwei; Xu, Hua; Zhao, Zhongming; Xie, Lei

    2016-01-01

    Metformin, a drug prescribed to treat type-2 diabetes, exhibits anti-cancer effects in a portion of patients, but the direct molecular and genetic interactions leading to this pleiotropic effect have not yet been fully explored. To repurpose metformin as a precision anti-cancer therapy, we have developed a novel structural systems pharmacology approach to elucidate metformin's molecular basis and genetic biomarkers of action. We integrated structural proteome-scale drug target identification with network biology analysis by combining structural genomic, functional genomic, and interactomic data. Through searching the human structural proteome, we identified twenty putative metformin binding targets and their interaction models. We experimentally verified the interactions between metformin and our top-ranked kinase targets. Notably, kinases, particularly SGK1 and EGFR were identified as key molecular targets of metformin. Subsequently, we linked these putative binding targets to genes that do not directly bind to metformin but whose expressions are altered by metformin through protein-protein interactions, and identified network biomarkers of phenotypic response of metformin. The molecular targets and the key nodes in genetic networks are largely consistent with the existing experimental evidence. Their interactions can be affected by the observed cancer mutations. This study will shed new light into repurposing metformin for safe, effective, personalized therapies. PMID:26841718

  14. Chronic anti-platelet therapy: a contraindication for platelet-rich plasma intra-articular injections?

    PubMed

    Di Matteo, B; Filardo, G; Lo Presti, M; Kon, E; Marcacci, M

    2014-01-01

    We report the case of a 50 years-old man who complained persisting knee pain that limited almost completely his sport performance. Since he previously underwent multiple aortocoronaric by-passes, he presented a chronic anti-aggregant therapy. In spite of this clinical history, he was still sport active and able to run long-distance races, until knee symptoms limited is activity level. Conservative treatment approaches proved to be unsuccessful, thus we decided to treat him by 3 Platelet-rich Plasma (PRP) injections even if chronic anti-aggregant therapy is generally regarded as a contra-indication for PRP, since this kind of drugs impairs platelet function and granules' release. Despite these premises, the clinical outcome was very satisfactory and the patient was able to rapidly resume intensive running activity. This experience opens new questions regarding the real potential of PRP in treating degenerative musculo-skeletal disorders, and in particular on its range of biological actions and on its limitations for clinical application. PMID:24825043

  15. Coaxial Electrospray of Ranibizumab-Loaded Microparticles for Sustained Release of Anti-VEGF Therapies

    PubMed Central

    Fischer, Andrew J.; Letson, Alan; Yuan, Shuai; Roberts, Cynthia J.; Xu, Ronald X.

    2015-01-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss and blindness in people over age 65 in industrialized nations. Intravitreous injection of anti-VEGF (vascular endothelial growth factor) therapies, such as ranibizumab (trade name: Lucentis), provides an effective treatment option for neovascular AMD. We have developed an improved coaxial electrospray (CES) process to encapsulate ranibizumab in poly(lactic-co-glycolic) acid (PLGA) microparticles (MPs) for intravitreous injection and sustained drug release. This microencapsulation process is advantageous for maintaining the stability of the coaxial cone-jet configurations and producing drug-loaded MPs with as high as 70% encapsulation rate and minimal loss of bioactivitiy. The utility of this emerging process in intravitreous drug delivery has been demonstrated in both benchtop and in vivo experiments. The benchtop test simulates ocular drug release using PLGA MPs encapsulating a model drug. The in vivo experiment evaluates the inflammation and retinal cell death after intravitreal injection of the MPs in a chick model. The experimental results show that the drug-load MPs are able to facilitate sustained drug release for longer than one month. No significant long term microglia reaction or cell death is observed after intravitreal injection of 200 μg MPs. The present study demonstrates the technical feasibility of using the improved CES process to encapsulate water-soluble drugs at a high concentration for sustained release of anti-VEGF therapy. PMID:26273831

  16. Insights into Neuroinflammation in Parkinson's Disease: From Biomarkers to Anti-Inflammatory Based Therapies

    PubMed Central

    Rocha, Natália Pessoa; de Miranda, Aline Silva; Teixeira, Antônio Lúcio

    2015-01-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide, being characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Among several putative factors that may contribute to PD pathogenesis, inflammatory mechanisms may play a pivotal role. The involvement of microglial activation as well as of brain and peripheral immune mediators in PD pathophysiology has been reported by clinical and experimental studies. These inflammatory biomarkers evaluated by imaging techniques and/or by biological sample analysis have become valuable tools for PD diagnosis and prognosis. Regardless of the significant increase in the number of people suffering from PD, there are still no established disease-modifying or neuroprotective therapies for it. There is growing evidence of protective effect of anti-inflammatory drugs on PD development. Herein, we reviewed the current literature regarding the central nervous system and peripheral immune biomarkers in PD and advances in diagnostic and prognostic tools as well as the neuroprotective effects of anti-inflammatory therapies. PMID:26295044

  17. Clinical features of active tuberculosis that developed during anti-tumor necrosis factor therapy in patients with inflammatory bowel disease

    PubMed Central

    Lee, Jang Wook; Park, Ji Hoon; Kim, Jeong Wook; Kang, Sang Bum; Koo, Ja Seol; Kim, Young-Ho; Kim, You Sun; Joo, Young Eun; Chang, Sae Kyung

    2016-01-01

    Background/Aims Anti-tumor necrosis factor (TNF) therapy for active ulcerative colitis (UC) and Crohn's disease (CD) is associated with increased risks of tuberculosis (TB) infection. We analyzed the incidence and clinical features of Korean patients with inflammatory bowel disease (IBD) who developed active TB during anti-TNF therapy. Methods Ten cases of active TB developed in patients treated with infliximab (n=592) or adalimumab (n=229) for UC (n=160) or CD (n=661) were reviewed. We analyzed demographics, interval between start of anti-TNF therapy and active TB development, tests for latent TB infection (LTBI), concomitant medications, and the details of diagnosis and treatments for TB. Results The incidence of active TB was 1.2% (10/821): 1.5% (9/592) and 0.4% (1/229) in patients receiving infliximab and adalimumab, respectively. The median time to the development of active TB after initiation of anti-TNF therapy was three months (range: 2–36). Three patients had past histories of treatment for TB. Positive findings in a TB skin test (TST) and/or interferon gamma releasing assay (IGRA) were observed in three patients, and two of them received anti-TB prophylaxis. Two patients were negative by both TST and IGRA. The most common site of active TB was the lungs, and the active TB was cured in all patients. Conclusions Active TB can develop during anti-TNF therapy in IBD patients without LTBI, and even in those with histories of TB treatment or LTBI prophylaxis. Physicians should be aware of the potential for TB development during anti-TNF therapy, especially in countries with a high prevalence of TB. PMID:27175115

  18. Phototherapy of psoriasis - clinical aspects and risk evaluation.

    PubMed

    Larkö, O

    1982-01-01

    The study gives information on the healing frequency and time to relapse in a day care centre for UVB, UVB plus dithranol, and PUVA treatment. Psoriasis treatment must be repeated for many years and a psoriasis patient must come to terms with the fact that during a substantial part of the rest of his life, he must use some type of treatment. This makes it important that the treatment is pleasant and easy to carry out. The combination of sauna and UVB in a day care centre, or treatment with home solaria fulfill these demands. In view of this background I think that UVB treatment of psoriasis could be the treatment of choice for many psoriasis patients. About 80 percent of the patients heal with this treatment. For the rest of the patients, addition of dithranol or a switch to PUVA has proven to be effective. Median time to healing was about 8 weeks with UVB and UVB + dithranol whereas 12 weeks was necessary to achieve healing among PUVA patients with a poor response to UVB given earlier. The remission times were 9, 12 and 25 weeks for UVB, UVB + dithranol and PUVA-treatment respectively. In Gothenburg, we give 35.000 UVB treatments annually. An important question is the potential hazards connected with the therapy as we know that UV radiation is carcinogenic. According to our studies, the median amount of UVB radiation actually received per year from therapy is of the same magnitude as during outdoor work or certain outdoor activities. If UVB treatment is expanded we can expect an increased incidence of skin cancer of squamous cell type among this type of psoriasis patient even if the retrospective study we made showed no increased risk among people extensively treated with UVB in the past. The risk for psoriasis patients on a life long UVB treatment will probably be of the same order of magnitude as for outdoor workers. In comparison with other every day risks, the risk of dying from a skin cancer seems to be negligible. Regular check-ups by a dermatologist can

  19. Osteopontin and adiponectin: how far are they related in the complexity of psoriasis?

    PubMed

    Kadry, D; Hegazy, R A; Rashed, L

    2013-12-01

    Increasing attention has been drawn towards the involvement of both osteopontin (OPN) and adiponectin in psoriasis. The relationship between them has been studied before in the context of essential hypertension. To our knowledge, whether a relation between them exists in cases of psoriasis and the metabolic status in such patients have not been investigated. We aimed to verify their possible roles and relations in psoriasis and its metabolic associations. 35 patients with psoriasis vulgaris and 35 controls were included. Patients were clinically assessed by PASI and investigated for the presence of metabolic syndrome (MetS) and/or its components. Plasma levels of OPN and adiponectin were measured using ELISA. On comparing psoriatics to controls, patients showed significantly elevated levels of OPN (90.474 ± 21.22 vs 34.709 ± 13.95 ng/mL) and significantly depressed levels of adiponectin (4,586 ± 1.187 vs 5,905 ± 1.374 ng/mL), (p < 0.001). Strong negative correlation between plasma OPN and adiponectin was detected in patients (r = -0.912, p < 0.001), but not in controls. OPN elevation was related to diabetes mellitus, insulin resistance, and MetS. Adiponectin depression was related to body mass index, and MetS. This study demonstrates for the first time a significant correlation between OPN and adiponectin in psoriasis, hypothesized to be mostly attributed to the inflammatory milieu of psoriasis and MetS as well as the enhanced renin-angiotensin-aldosterone system previously documented in psoriasis. Adjuvant therapies aiming at modulating levels of OPN and adiponectin are speculated to add benefit in psoriasis treatment and protecting against its metabolic risks. PMID:23884541

  20. Psoriasis beyond the skin surface: a pilot study on the ocular involvement.

    PubMed

    Campanati, A; Neri, P; Giuliodori, K; Arapi, I; Carbonari, G; Borioni, E; Herbort, C P; Mariotti, C; Giovannini, A; Offidani, A

    2015-06-01

    The ocular involvement in psoriasis is not a completely well-known problem. The ophthalmologic involvement occurs in about 10 % of patients, particularly in case of arthropathic or pustular psoriasis. Ocular lesions are more common in males, and they often occur during psoriasis exacerbations. Our study aimed to assess the prevalence and type of ocular involvement in psoriasis, by a comparison between psoriasis and healthy subjects, and if/how a 12-week long systemic immunosuppressive therapy is able to modify them. This study involved thirty-two psoriatic patients and thirty-two healthy subjects. Dermatological evaluation was done using Psoriasis Area and Severity Index, Physician Global Assessment, and Dermatology Life Quality Index (PASI, PGA, and DLQI score). Ophthalmological evaluation included ocular surface involvement (Schirmer, Jones, break-up time--BUT, DR-1 camera), retinal pathologies, and ocular surface disease index. Laboratory investigations including the C-reactive protein (CRP) of all the patients were performed. At baseline, the values of Schirmer, Jones, and BUT tests in the patient group were significantly lower compared to controls; moreover, conjunctival hyperemia was more frequent in psoriatic patients than in healthy subjects. Ocular involvement was more prominent in the subset of psoriatic patients with sebo-psoriasis than in general psoriatic population. A statistically significant correlation was found in sebo-psoriasis between PASI and Schirmer, between PASI and Jones, and between PASI and BUT. On the other hand, the results obtained from DR1 camera showed statistically significant difference between psoriatic and sebo-psoriatic patients at the end of the follow-up. After 12 weeks of treatment, the mean values of PASI, PGA, DLQI, CRP, and BUT showed significant changes in psoriatic patients. Our findings suggest a high rate of ocular involvement in psoriatic patients, emphasizing the need of performing periodic ophthalmological

  1. Photo-thermal therapy of bladder cancer with Anti-EGFR antibody conjugated gold nanoparticles.

    PubMed

    Chen, Chieh Hsiao; Wu, Yi-Jhen; Chen, Jia-Jin

    2016-01-01

    The aim of this study was to enhance the effectiveness of photo thermal therapy (PTT) in the targeting of superficial bladder cancers using a green light laser in conjunction with gold nanoparticles (GNPs) conjugated to antibody fragments (anti-EGFR). GNPs conjugated with anti-EGFR-antibody fragments were used as probes in the targeting of tumor cells and then exposed to a green laser (532nm), resulting in the production of sufficient thermal energy to kill urothelial carcinomas both in vitro and in vivo. Nanoparticles conjugated with antibody fragments are capable of damaging cancer cells even at relatively very low energy levels, while non-conjugated nanoparticles would require an energy level of 3 times under the same conditions. The lower energy required by the nanoparticles allows this method to destroy cancerous cells while preserving normal cells when applied in vivo. Nanoparticles conjugated with antibody fragments (anti-EGFR) require less than half the energy of non-conjugated nanoparticles to kill cancer cells. In an orthotopic bladder cancer model, the group treated using PTT presented significant differences in tumor development. PMID:27100501

  2. Anti-vascular endothelial growth factor therapies in ophthalmology: current use, controversies and the future

    PubMed Central

    Kwong, Tsong Qiang; Mohamed, Moin

    2014-01-01

    Use of anti-vascular endothelial growth factor (VEGF) therapies was introduced for the treatment of ocular disorders in 2005. In the UK, the current licensed and NICE approved indications are for the treatment of neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DMO), macular oedema secondary to a retinal vein occlusion (RVO) and choroidal neovascularization in pathological myopia. These diagnoses alone account for two-thirds of the main causes of legally registrable visual impairment and blindness. Ranibizumab (Lucentis®; Genentech/Novartis), a drug specifically designed for intraocular use, is the primary licensed medication. Controversially however, clinicians have been using an unlicensed cheaper drug, bevacizumab (Avastin®; Genentech/Roche), originally designed for systemic administration, with a similar mode of action and shown to have a similar efficacy. However, there are fears of greater side effects with bevacizumab though studies have not been sufficiently powered to show statistical difference. In the current global economic climate, anti-VEGF treatment places huge financial and logistical pressure on already strained health care systems. Bevacizumab is considerably more cost effective than ranibizumab, and thus using bevacizumab would widen access to treatment particularly in developing countries. This licensing issue also places clinicians in a difficult medico-legal position especially in Europe, where doctors are duty bound to use a licensed drug for a particular indication if this is available. As the indications of anti-VEGF therapies expand and the cost of health care provision becomes more expensive, the controversies surrounding their use will inevitably become more important. PMID:24602183

  3. Combining T-cell immunotherapy and anti-androgen therapy for prostate cancer

    PubMed Central

    Sanchez, C; Chan, R; Bajgain, P; Rambally, S; Palapattu, G; Mims, M; Rooney, CM; Leen, AM; Brenner, MK; Vera, JF

    2013-01-01

    BACKGROUND Prostate cancer remains a significant health problem for men in the Western world. Although treatment modalities are available, these do not confer long-term benefit and are accompanied by substantial side effects. Adoptive immunotherapy represents an attractive alternative to conventional treatments as a means to control tumor growth. METHODS To selectively target the tumor-expressed form of Muc1 we constructed a retroviral vector encoding a chimeric antigen receptor (CAR) directed against the aberrantly-expressed extracellular portion of Muc1 called the ‘variable number of tandem repeats’. RESULTS We now demonstrate that T cells can be genetically engineered to express a CAR targeting the tumor-associated antigen Muc1. CAR-Muc1 T cells were able to selectively kill Muc1-expressing human prostate cancer cells. However, we noted that heterogeneous expression of the Muc1 antigen on tumor cells facilitated immune escape and the outgrowth of target-antigen loss variants of the tumor. Given the importance of androgen ablation therapy in the management of metastatic prostate cancer, we therefore also tested the value of combining conventional (anti-androgen) and experimental (CAR-Muc1 T cells) approaches. We show that CAR-Muc1 T cells were not adversely impacted by anti-androgen therapy and subsequently demonstrate the feasibility of combining the approaches to produce additive anti-tumor effects in vitro. CONCLUSIONS Adoptive transfer of CAR-Muc1 T cells alone or in combination with other luteinizing hormone-releasing hormone analogs or antagonists should be tested in human clinical trials. PMID:23295316

  4. Effective and sustainable biologic treatment of psoriasis: what can we learn from new clinical data?

    PubMed

    Langley, R G

    2012-03-01

    The introduction of the biologic agents, adalimumab, etanercept, infliximab and ustekinumab, has provided more options for the short- and long-term treatment of patients with psoriasis. Physicians are now able to achieve and maintain effective disease control in more patients using biologic therapies. Newly published clinical data support the introduction of novel optimization strategies to further improve outcomes in patients with psoriasis. Recent randomized controlled clinical trials have provided data on the efficacy of conventional therapies, including systemic agents, and biologics at specific time points. Switching from methotrexate to a tumour necrosis factor (TNF)-α antagonist after 16 weeks can improve response rates, as demonstrated in a study of patients with moderate-to-severe psoriasis, while the benefit of long-term methotrexate use remains unclear. In a separate study, psoriasis area and severity index (PASI) ≥ 75 response rates were maintained over time (>3 years for adalimumab), suggesting that long-term biologic therapy is an effective and sustainable treatment option for psoriasis. For each individual patient, the benefit of a particular treatment needs to be balanced with the risks. The lack of head-to-head trials of antipsoriatic therapies, particularly biologic therapies, does not help with making individualized treatment decisions. However, a benefit-risk assessment of TNF-α antagonists calculated from an integrated analysis of published literature in moderate-to-severe psoriasis can be used to aid clinical practice. The number needed to treat, number needed to harm and number of patient years of observation to detect an adverse event have been determined for adalimumab, etanercept and infliximab. The benefit-risk profiles generated demonstrated that, during the initial year of treatment, likelihood of success with TNF-α antagonists was several orders of magnitude greater than the likelihood of serious toxicity. PMID:22356632

  5. Depression and Insomnia in Patients With Psoriasis and Psoriatic Arthritis Taking Tumor Necrosis Factor Antagonists

    PubMed Central

    Wu, Chun-Ying; Chang, Yun-Ting; Juan, Chao-Kuei; Shen, Jui-Lung; Lin, Yu-Pu; Shieh, Jeng-Jer; Liu, Han-Nan; Chen, Yi-Ju

    2016-01-01

    Abstract Psoriasis patients with moderate to severe disease often present with depression and insomnia. Treatment targeting both psoriasis and psychological comorbidities is needed to improve the quality of life of these patients. In this nationwide cohort study, a total of 980 patients with psoriatic arthritis or psoriasis who had received nonbiological disease-modifying antirheumatic drugs and biologics therapy between 2009 and 2012 were identified. The prevalence rates of patients taking medications for depression and insomnia were compared before and after biologics therapy. Logistic regression method was used to investigate the risk factors for depression and insomnia. Further stratified analyses were performed to examine the prevalence of use of medications for depression and insomnia among different patient subgroups. The prevalence of patients taking regular antidepressants before starting biologics therapy was about 20%. There was a more than 40% reduction in this prevalence after biologics therapy for 2 years. Age higher than 45 years, female sex, presence of comorbidities, and psoriatic arthritis were independently associated with depression and insomnia. Further stratified analyses revealed a more rapid and significant reduction in depression/insomnia in those undergoing continuous biologics therapy, younger than 45 years, without psoriatic arthritis and not taking concomitant methotrexate, when compared with their counterparts. The results suggest that biologics therapy may be associated with reduced rates of depression and insomnia, and a reduced rate of regular antidepressants use in psoriasis patients. PMID:27258525

  6. Biologics in the management of psoriasis

    PubMed Central

    Bahner, Jennifer D; Cao, Lauren Y; Korman, Neil J

    2009-01-01

    Psoriasis is a chronic inflammatory systemic disease for which there exist topical, ultraviolet, systemic, and biologic treatments. Biologic agents selectively interfere with the immune mechanisms responsible for psoriasis. Etanercept, infliximab, and adalimumab target tumor necrosis factor-alpha and have demonstrated efficacy in the treatment of psoriasis and psoriatic arthritis. Alefacept and efalizumab target T lymphocytes, are effective in the treatment of psoriasis, but are not approved for psoriatic arthritis. Finally, ustekinumab and ABT-874 target interleukin-12 and interleukin-23, and they have demonstrated efficacy in the treatment of psoriasis. The objective of this review is to present efficacy and safety data from randomized controlled trials of the biologic agents in the treatment of psoriasis. PMID:21436974

  7. Anti-PD-1/PD-L1 antibody therapy for pretreated advanced nonsmall-cell lung cancer

    PubMed Central

    Zhou, Guo-Wu; Xiong, Ye; Chen, Si; Xia, Fan; Li, Qiang; Hu, Jia

    2016-01-01

    Abstract Background: Anti-PD-1/PD-L1 antibody therapy is a promising clinical treatment for nonsmall-cell lung cancer (NSCLC). However, whether anti-PD-1/PD-L1 antibody therapy can provide added benefits for heavily pretreated patients with advanced NSCLC and whether the efficacy of anti-PD-1/PD-L1 antibody therapy relates to the tumor PD-L1 expression level remain controversial. Thus, this meta-analysis evaluated the efficacy and safety of anti-PD-1/PD-L1 antibody therapy for pretreated patients with advanced NSCLC. Methods: Randomized clinical trials were retrieved by searching the PubMed, EMBASE, ASCO meeting abstract, clinicaltrial.gov, and Cochrane library databases. The pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios for the overall response rate and adverse events (AEs) were calculated by STATA software. Results: Three randomized clinical trials involving 1141 pretreated patients with advanced NSCLC were included. These trials all compared the efficacy and safety of anti-PD-1/PD-L1 antibodies (nivolumab and MPDL3280A) with docetaxel. The results suggested that, for all patients, anti-PD-1/PD-L1 therapy could acquire a greater overall response (odds ratio = 1.50, 95% CI: 1.08–2.07, P = 0.015, P for heterogeneity [Ph] = 0.620) and longer OS (HR = 0.71, 95% CI: 0.61–0.81, P < 0.001, Ph = 0.361) than docetaxel, but not PFS (HR = 0.83, 95% CI: 0.65–1.06, P = 0.134; Ph = 0.031). Subgroup analyses according to the tumor PD-L1 expression level showed that anti-PD-1/PD-L1 therapy could significantly improve both OS and PFS in patients with high expressions of PD-L1, but not in those with low expressions. Generally, the rates of grade 3 or 4 AEs of anti-PD-1/PD-L1 therapy were significantly lower than that of docetaxel. However, the risks of pneumonitis and hypothyroidism were significantly higher. Conclusion: Anti-PD-1/PD-L1 antibody therapy may significantly improve

  8. Endothelialization of drug eluting stents and its impact on dual anti-platelet therapy duration.

    PubMed

    Habib, Anwer; Finn, Aloke V

    2015-03-01

    Coronary artery disease is a leading cause of death and disability worldwide with contemporary treatment strategies employing both optimal medical therapy and catheter based percutaneous coronary intervention (PCI) with drug eluting stents (DES). While DES have dramatically reduced restenosis rates, their use has been associated with an increased risk of late stent thrombosis and accelerated neointimal atherosclerosis (i.e. "neoatherosclerosis") both major contributors to late stent failure. The underlying substrate of late DES failure is likely related to vascular endothelial dysfunction such as poor endothelial regrowth and barrier function (i.e. "endothelial healing"). Initial concerns with 1st generation DES have lead to improvements in mechanical and biologic properties of current 2nd generation DES, which inhibit endothelial regrowth to a lesser extent, lessening late stent failure and resulting in an overall improved safety profile. Current guidelines recommend duration of at least one year of dual anti-platelet therapy with aspirin and a thienopyridine agent such as clopidogrel or prasugrel as sufficient to prevent late thrombotic complications. Recent studies, however, suggest a shorter duration of dual anti-platelet therapy may be equally as safe and efficacious in preventing stent thrombosis with newer generation DES. However, higher risk populations such as patients receiving 1st generation DES or those with increased risk for future ischemic events may benefit from a longer duration (i.e. 30 months) of DAPT to prevent major cardiovascular events with the caveat that such an approach may be associated with an increased risk for bleeding. This review examines the vascular responses to 1st and second generation DES and recent clinical trials examining DAPT duration. PMID:25533811

  9. Non-Invasive Imaging for Studying Anti-Angiogenic Therapy Effects

    PubMed Central

    Ehling, Josef; Lammers, Twan; Kiessling, Fabian

    2013-01-01

    Noninvasive imaging plays an emerging role in preclinical and clinical cancer research and has high potential to improve clinical translation of new drugs. This article summarizes and discusses tools and methods to image tumor angiogenesis and monitor anti-angiogenic therapy effects. In this context, micro-computed tomography (μCT) is recommended to visualize and quantify the micro-architecture of functional tumor vessels. Contrast-enhanced ultrasound (US) and magnetic resonance imaging (MRI) are favorable tools to assess functional vascular parameters, such as perfusion and relative blood volume. These functional parameters have been shown to indicate anti-angiogenic therapy response at an early stage, before changes in tumor size appear. For tumor characterization, the imaging of the molecular characteristics of tumor blood vessels, such as receptor expression, might have an even higher diagnostic potential and has been shown to be highly suitable for therapy monitoring as well. In this context, US using targeted microbubbles is currently evaluated in clinical trials as an important tool for the molecular characterization of the angiogenic endothelium. Other modalities, being preferably used for molecular imaging of vessels and their surrounding stroma, are photoacoustic imaging (PAI), near-infrared fluorescence optical imaging (OI), MRI, positron emission tomography (PET) and single photon emission computed tomography (SPECT). The latter two are particularly useful if very high sensitivity is needed, and/or if the molecular target is difficult to access. Carefully considering the pros and cons of different imaging modalities in a multimodal imaging setup enables a comprehensive longitudinal assessment of the (micro)morphology, function and molecular regulation of tumor vessels. PMID:23407722

  10. IFN-α subtypes: distinct biological activities in anti-viral therapy

    PubMed Central

    Gibbert, K; Schlaak, JF; Yang, D; Dittmer, U

    2013-01-01

    During most viral infections, the immediate host response is characterized by an induction of type I IFN. These cytokines have various biological activities, including anti-viral, anti-proliferative and immunomodulatory effects. After induction, they bind to their IFN-α/β receptor, which leads to downstream signalling resulting in the expression of numerous different IFN-stimulated genes. These genes encode anti-viral proteins that directly inhibit viral replication as well as modulate immune function. Thus, the induction of type I IFN is a very powerful tool for the host to fight virus infections. Many viruses evade this response by various strategies like the direct suppression of IFN induction or inhibition of the IFN signalling pathway. Therefore, the therapeutic application of exogenous type I IFN or molecules that induce strong IFN responses should be of great potential for future immunotherapies against viral infections. Type I IFN is currently used as a treatment in chronic hepatitis B and C virus infection, but as yet is not widely utilized for other viral infections. One reason for this restricted clinical use is that type I IFN belongs to a multigene family that includes 13 different IFN-α subtypes and IFN-β, whose individual anti-viral and immunomodulatory properties have so far not been investigated in detail to improve IFN therapy against viral infections in humans. In this review, we summarize the recent achievements in defining the distinct biological functions of type I IFN subtypes in cell culture and in animal models of viral infection as well as their clinical usage in chronic hepatitis virus infections. PMID:23072338

  11. A cost–utility analysis of etanercept for the treatment of moderate-to-severe psoriasis in Italy

    PubMed Central

    Colombo, Giorgio L; Di Matteo, Sergio; Peris, Ketty; Fargnoli, Maria Concetta; Esposito, Maria; Mazzotta, Annamaria; Chimenti, Sergio

    2009-01-01

    Introduction: Biologic therapies have proven efficacious for patients with moderate-to-severe psoriasis. However, their economic value compared with standard of care in Italy has not been explored. This study estimates the cost-effectiveness of intermittent therapy with etanercept in patients with moderate-to-severe plaque-type psoriasis in comparison with nonsystemic therapy in Italy. Methods: This study employs cost–utility analysis using a Markov model adapted from the British “York model”. It compares the cost per quality-adjusted life-year (QALY) of intermittent etanercept (25 mg twice weekly) versus nonsystemic therapy. Data on efficacy and changes in quality of life were derived from three etanercept clinical trials. Direct costs of treating psoriasis patients, including hospitalizations and dermatology clinic visits, were taken from an Italian cost-of-illness study. Extrapolations were made to evaluate the cost-effectiveness of intermittent etanercept versus nonsystemic therapy over a period of ten years. Results: For the group of patients with moderate and severe plaque psoriasis (initial Psoriasis Area and Severity Index [PASI ≥ 10]) the incremental cost-effectiveness ratio (ICER) for etanercept compared with nonsystemic therapy was €33,216/QALY; for the group of patients with severe psoriasis (PASI ≥ 20), the ICER was €25,486/QALY. Conclusions: Within the Italian health care system, intermittent etanercept is a cost-effective therapeutic option compared with nonsystemic therapy for the group of patients with moderate and severe plaque psoriasis. For patients with PASI ≥ 20, cost-effectiveness of etanercept is even greater. PMID:21935307

  12. Use of tumor necrosis factor alpha (TNF α) antagonists in a patient with psoriasis and Chagas disease*

    PubMed Central

    Navarrete-Dechent, Cristián; Majerson, Daniela; Torres, Marisa; Armijo, Daniela; Patel, Mahir; Menter, Alan; de la Cruz, Claudia

    2015-01-01

    There are several studies on the benefits of using TNFα antagonists in the treatment of psoriasis, but few studies addressing the interaction of these drugs with chronic infections. We report the case of a 52-year-old patient diagnosed with psoriasis refractory to traditional systemic agents, who was treated with biologic therapies. After one year of treatment with biologic agents, the patient was diagnosed with Chagas Disease. PMID:26312707

  13. Use of tumor necrosis factor alpha (TNF α) antagonists in a patient with psoriasis and Chagas disease.

    PubMed

    Navarrete-Dechent, Cristián; Majerson, Daniela; Torres, Marisa; Armijo, Daniela; Patel, Mahir; Menter, Alan; de la Cruz, Claudia

    2015-01-01

    There are several studies on the benefits of using TNFα antagonists in the treatment of psoriasis, but few studies addressing the interaction of these drugs with chronic infections. We report the case of a 52-year-old patient diagnosed with psoriasis refractory to traditional systemic agents, who was treated with biologic therapies. After one year of treatment with biologic agents, the patient was diagnosed with Chagas Disease. PMID:26312707

  14. Myelodysplastic Syndrome Revealed by Systems Immunology in a Melanoma Patient Undergoing Anti-PD-1 Therapy.

    PubMed

    Greenplate, Allison R; Johnson, Douglas B; Roussel, Mikael; Savona, Michael R; Sosman, Jeffrey A; Puzanov, Igor; Ferrell, P Brent; Irish, Jonathan M

    2016-06-01

    Antibodies aimed at blocking the interaction between programmed cell death-1 (PD-1) and its ligands have shown impressive efficacy in a variety of malignancies and are generally well tolerated. Research has focused intensely on T cells and their interaction with cells within melanoma tumors, while relatively little is understood about the systems immunology of the cells in the blood during checkpoint inhibitor therapy. Longitudinal cytomic analysis using mass cytometry can characterize all the cells in a small sample of blood and has the potential to reveal key shifts in the cellular milieu occurring during treatment. We report a case of advanced melanoma in which mass cytometry detected abnormal myeloid cells resulting from myelodysplastic syndrome (MDS) in the blood following treatment with an anti-PD-1 agent. Myeloid blasts comprised <1% of peripheral blood mononuclear cells (PBMC) 1 month after the start of treatment. Six months after starting therapy, myeloid blasts comprised 5% of PBMCs, and a bone marrow biopsy confirmed refractory anemia with excess blasts-2 (RAEB-2). Longitudinal mass cytometry immunophenotyping comprehensively characterized blast phenotype evolution and revealed elevated PD-1 expression on the surface of nonblast myeloid cells. These findings highlight the clinical significance of cytomic monitoring, indicate that the myeloid compartment should be monitored during checkpoint inhibitor therapy, and emphasize the value of systems immunology in medicine. Cancer Immunol Res; 4(6); 474-80. ©2016 AACR. PMID:26966176

  15. Newcastle disease virus, rituximab, and doxorubicin combination as anti-hematological malignancy therapy

    PubMed Central

    Al-Shammari, Ahmed Majeed; Rameez, Huda; Al-Taee, Maha F

    2016-01-01

    Hematological malignancies are important diseases that need more powerful therapeutics. Even with current targeting therapies, such as rituximab and other chemotherapeutic agents, there is a need to develop new treatment strategies. Combination therapy seems the best option to target the tumor cells by different mechanisms. Virotherapy is a very promising treatment modality, as it is selective, safe, and causes cancer destruction. The Iraqi strain of Newcastle disease virus (NDV) has proved to be effective both in vitro and in vivo. In the current work, we tested its ability on anti-hematological tumors and enhanced current treatments with combination therapy, and studied this combination using Chou–Talalay analysis. p53 concentration was measured to evaluate the mechanism of this proposed synergism. The results showed that NDV was synergistic with doxorubicin in low doses on plasmacytoma cells, with no involvement of p53 pathways, but involved p53 when the combination was used on non-Hodgkin lymphoma cells. NDV in combination with rituximab showed enhanced cytotoxicity that was p53-independent. In conclusion, this work proposes a novel combination modality for treatment of some hematological malignancies. PMID:27579294

  16. Cytokine and anti-cytokine therapies in prevention or treatment of fibrosis in IBD.

    PubMed

    Jacob, Noam; Targan, Stephan R; Shih, David Q

    2016-08-01

    The frequency of fibrosing Crohn's disease (CD) is significant, with approximately 40% of CD patients with ileal disease developing clinically apparent strictures throughout their lifetime. Although strictures may be subdivided into fibrotic, inflammatory, or mixed forms, despite immunosuppressive therapy in CD patients in the form of steroids or immunomodulators, the frequency of fibrostenosing complications has still remained significant. A vast number of genetic and epigenetic variables are thought to contribute to fibrostenosing disease, including those that affect cytokine biology, and therefore highlight the complexity of disease, but also shed light on targetable pathways. Exclusively targeting fibrosis may be difficult, however, because of the relatively slow evolution of fibrosis in CD, and the potential adverse effects of inhibiting pathways involved in tissue repair and mucosal healing. Acknowledging these caveats, cytokine-targeted therapy has become the mainstay of treatment for many inflammatory conditions and is being evaluated for fibrotic disorders. The question of whether anti-cytokine therapy will prove useful for intestinal fibrosis is, therefore, acutely relevant. This review will highlight some of the current therapeutics targeting cytokines involved in fibrosis. PMID:27536363

  17. Cytokine and anti-cytokine therapies in prevention or treatment of fibrosis in IBD

    PubMed Central

    Jacob, Noam; Targan, Stephan R

    2016-01-01

    The frequency of fibrosing Crohn’s disease (CD) is significant, with approximately 40% of CD patients with ileal disease developing clinically apparent strictures throughout their lifetime. Although strictures may be subdivided into fibrotic, inflammatory, or mixed forms, despite immunosuppressive therapy in CD patients in the form of steroids or immunomodulators, the frequency of fibrostenosing complications has still remained significant. A vast number of genetic and epigenetic variables are thought to contribute to fibrostenosing disease, including those that affect cytokine biology, and therefore highlight the complexity of disease, but also shed light on targetable pathways. Exclusively targeting fibrosis may be difficult, however, because of the relatively slow evolution of fibrosis in CD, and the potential adverse effects of inhibiting pathways involved in tissue repair and mucosal healing. Acknowledging these caveats, cytokine-targeted therapy has become the mainstay of treatment for many inflammatory conditions and is being evaluated for fibrotic disorders. The question of whether anti-cytokine therapy will prove useful for intestinal fibrosis is, therefore, acutely relevant. This review will highlight some of the current therapeutics targeting cytokines involved in fibrosis.

  18. Newcastle disease virus, rituximab, and doxorubicin combination as anti-hematological malignancy therapy.

    PubMed

    Al-Shammari, Ahmed Majeed; Rameez, Huda; Al-Taee, Maha F

    2016-01-01

    Hematological malignancies are important diseases that need more powerful therapeutics. Even with current targeting therapies, such as rituximab and other chemotherapeutic agents, there is a need to develop new treatment strategies. Combination therapy seems the best option to target the tumor cells by different mechanisms. Virotherapy is a very promising treatment modality, as it is selective, safe, and causes cancer destruction. The Iraqi strain of Newcastle disease virus (NDV) has proved to be effective both in vitro and in vivo. In the current work, we tested its ability on anti-hematological tumors and enhanced current treatments with combination therapy, and studied this combination using Chou-Talalay analysis. p53 concentration was measured to evaluate the mechanism of this proposed synergism. The results showed that NDV was synergistic with doxorubicin in low doses on plasmacytoma cells, with no involvement of p53 pathways, but involved p53 when the combination was used on non-Hodgkin lymphoma cells. NDV in combination with rituximab showed enhanced cytotoxicity that was p53-independent. In conclusion, this work proposes a novel combination modality for treatment of some hematological malignancies. PMID:27579294

  19. Coexistence of psoriasis with bullous pemphigoid

    PubMed Central

    Rao, Raghavendra; Gupta, Akash; Yunis, Fousiya; Handettu, Sripathi; Chandrashekar, Balachandran

    2012-01-01

    Psoriasis vulgaris and bullous pemphigoid (BP) represent two clinically well-characterized, chronic, inflammatory skin conditions. The concomitant occurrence of these two entities in a patient is rare. Here we report a 57-year-old male suffering from psoriasis vulgaris for 15 years on irregular medication who noticed eruption of blisters all over the body. We believe that this is the first case report of psoriasis vulgaris coexistent with bullous pemphigoid in Indian literature. Please check where you want bullous pemphigoid and where you want psoriasis pemphigoides. PMID:23130285

  20. Clopidogrel: A possible exacerbating factor for psoriasis

    PubMed Central

    Mahajan, Vikram K.; Khatri, Gayatri; Prabha, Neel; Abhinav, C.; Sharma, Vikas

    2014-01-01

    A 64-year-old man developed palmoplantar pustulosis eventuating into palmoplantar pustular psoriasis following treatment with diltiazem, atenolol, aspirin and atorvastatin for suspected coronary artery disease (CAD). Treatment for psoriasis, stopping atenolol and substituting aspirin with clopidogrel did not benefit. Subsequently, he stopped all his drugs and did not develop psoriasis or symptoms/signs of CAD. Re-challenge with oral clopidogrel precipitated his skin lesions. This case has implications for patients having psoriasis and cardiovascular comorbidity where clopidogrel/ticlopidine or aspirin may not be a useful alternative. PMID:24550599

  1. Clopidogrel: a possible exacerbating factor for psoriasis.

    PubMed

    Mahajan, Vikram K; Khatri, Gayatri; Prabha, Neel; Abhinav, C; Sharma, Vikas

    2014-01-01

    A 64-year-old man developed palmoplantar pustulosis eventuating into palmoplantar pustular psoriasis following treatment with diltiazem, atenolol, aspirin and atorvastatin for suspected coronary artery disease (CAD). Treatment for psoriasis, stopping atenolol and substituting aspirin with clopidogrel did not benefit. Subsequently, he stopped all his drugs and did not develop psoriasis or symptoms/signs of CAD. Re-challenge with oral clopidogrel precipitated his skin lesions. This case has implications for patients having psoriasis and cardiovascular comorbidity where clopidogrel/ticlopidine or aspirin may not be a useful alternative. PMID:24550599

  2. Psoriasis and sleep disorders: A systematic review.

    PubMed

    Gupta, Madhulika A; Simpson, Fiona C; Gupta, Aditya K

    2016-10-01

    Psoriasis is an immune-mediated chronic inflammatory disorder which manifests as dermatologic lesions, and psoriatic arthritis (PsA) in about 30% of cases. Psoriasis is associated with multiple comorbidities including metabolic syndrome, hypertension, diabetes, cardiovascular events, obesity and psychiatric disorders, which can all affect the course of sleep disorders. A systematic review of the literature on the relationship between psoriasis, PsA, and formal sleep disorders identified 33 studies. There is an increased prevalence of obstructive sleep apnea (OSA) with 36%-81.8% prevalence in psoriasis versus 2%-4% in the general population. There was also an increase in the prevalence of restless legs syndrome of 15.1%-18% in psoriasis versus 5%-10% in European and North American samples. The wide variety of insomnia criteria used in studies resulted in an insomnia prevalence of 5.9%-44.8% in psoriasis, which is insufficient to show an elevated prevalence when the general population has a 10% prevalence of chronic insomnia and 30-35% prevalence of transient insomnia. There is evidence that symptoms of insomnia in psoriasis are directly mediated by pruritus and pain. Treatments that decrease the cutaneous symptoms in psoriasis were successful in mitigating insomnia, but did not show improvements in OSA where the relationship with psoriasis is multifactorial. PMID:26624228

  3. Apremilast: A Review in Psoriasis and Psoriatic Arthritis.

    PubMed

    Deeks, Emma D

    2015-08-01

    Apremilast (Otezla(®)) is an oral phosphodiesterase 4 inhibitor indicated for the twice-daily treatment of adults with psoriasis and psoriatic arthritis (PsA). Its use in these patient populations has been assessed in two phase III clinical trial programmes (ESTEEM and PALACE). At 16 weeks in the two ESTEEM trials, apremilast reduced the severity and extent of moderate to severe plaque psoriasis, including nail, scalp and palmoplantar manifestations, versus placebo in adults, with these benefits generally being sustained over 52 weeks of treatment. Similarly, in three PALACE trials (PALACE 1-3), apremilast improved the signs and symptoms of PsA relative to placebo at 16 weeks in adults with active disease despite treatment with conventional synthetic and/or biologic disease-modifying anti-rheumatic drugs. These PsA benefits were generally sustained for up to 104 weeks of treatment; skin involvement, enthesitis and dactylitis also improved with the drug. Apremilast was generally well tolerated, with the most common adverse events being diarrhoea and nausea in the first year of treatment (usually occurring in the first 2 weeks after the first dose and resolving within 4 weeks) and nasopharyngitis and upper respiratory tract infection with continued treatment. Although further longer-term and comparative efficacy and tolerability data would be beneficial, the current clinical data indicate that apremilast is an effective and well tolerated option for the management of psoriasis and PsA in adults. PMID:26220911

  4. Improved Treatment of Breast Cancer with Anti-HER2 Therapy Requires Interleukin-21 Signaling in CD8+ T Cells.

    PubMed

    Mittal, Deepak; Caramia, Franco; Michiels, Stefan; Joensuu, Heikki; Kellokumpu-Lehtinen, Pirkko-Liisa; Sotiriou, Christos; Loi, Sherene; Smyth, Mark J

    2016-01-15

    The HER2/ErbB2 monoclonal antibody (mAb) trastuzumab is combined with chemotherapy as a standard-of-care for newly diagnosed HER2(+) breast cancer patients, but some patients treated with this combination therapy experience early relapse. Our analysis of data from a clinical trial evaluating the efficacy of chemotherapy plus/minus trastuzumab suggested that the magnitude of trastuzumab benefit on distant disease-free survival was higher for increasing expression of the IL21 receptor (IL21R). Therefore, we investigated a possible role for IL21 signaling in promoting HER2 mAb therapeutic efficacy. We found that IL21R-deficient mice and wild-type mice treated with a neutralizing anti-IL21 mAb were less susceptible to trastuzumab-like anti-ErbB2 therapy. Furthermore, IL21R expression on CD8(+) T cells, but not on natural killer cells, was required for optimal anti-ErbB2 mAb efficacy, and IL21 expression was enhanced in tumor-infiltrating CD4(+) T lymphocytes after anti-ErbB2 therapy. Finally, we found that administering recombinant IL21 in combination with anti-ErbB2 therapy was therapeutic against primary tumors and experimental metastases in mice. Collectively, our findings suggest that elevating IL21 signaling may enhance trastuzumab efficacy, thus constituting a novel candidate strategy to overcome trastuzumab resistance and improve patient survival. Cancer PMID:26744522

  5. Cost of poor adherence to anti-hypertensive therapy in five European countries.

    PubMed

    Mennini, F S; Marcellusi, A; von der Schulenburg, J M Graf; Gray, A; Levy, P; Sciattella, P; Soro, M; Staffiero, G; Zeidler, J; Maggioni, A; Schmieder, R E

    2015-01-01

    The financial burden for EU health systems associated with cardiovascular disease (CV) has been estimated to be nearly €110 billion in 2006, corresponding to 10% of total healthcare expenditure across EU or a mean €223 annual cost per capita. The main purpose of this study is to estimate the costs related to hypertension and the economic impact of increasing adherence to anti-hypertensive therapy in five European countries (Italy, Germany, France, Spain and England). A probabilistic prevalence-based decision tree model was developed to estimate the direct costs of CV related to hypertension (CV defined as: stroke, heart attack, heart failure) in five European countries. Our model considered adherence to hypertension treatment as a main driver of blood pressure (BP) control (BP < 140/90 mmHg). Relative risk of CV, based on controlled or uncontrolled BP group, was estimated from the Framingham Heart Study and national review data. Prevalence and cost data were estimated from national literature reviews. A national payer (NP) perspective for 10 years was considered. Probabilistic sensitivity analysis was performed in order to evaluate uncertainty around the results (given as 95% confidence intervals). The model estimated a total of 8.6 million (1.4 in Italy, 3.3 in Germany, 1.2 in Spain, 1.8 in France and 0.9 in England) CV events related to hypertension over the 10-year time horizon. Increasing the adherence rate to anti-hypertensive therapy to 70% (baseline value is different for each country) would lead to 82,235 fewer CV events (24,058 in Italy, 7,870 in Germany, 18,870 in Spain, 24,855 in France and 6,553 in England). From the NP perspective, the direct cost associated with hypertension was estimated to be 51.3 billion (8.1 in Italy, 17.1 in Germany, 12.2 in Spain, 8.8 in France and 5.0 in England). Increasing adherence to anti-hypertensive therapy to 70% would save a total of 332 million (CI 95%: €319-346 million) from the NPs perspective. This

  6. Optimum scratch assay condition to evaluate connective tissue growth factor expression for anti-scar therapy.

    PubMed

    Moon, Heekyung; Yong, Hyeyoung; Lee, Ae-Ri Cho

    2012-02-01

    To evaluate a potential anti-scar therapy, we first need to have a reliable in vitro wound model to understand dermal fibroblast response upon cell injury and how cytokine levels are changed upon different wound heal phases. An in vitro wound model with different scratch assay conditions on primary human foreskin fibroblast monolayer cultures was prepared and cytokine levels and growth properties were evaluated with the aim of determining optimum injury conditions and observation time. Morphological characteristics of differently scratched fibroblasts from 0 to 36 h post injury (1 line, 2 lines and 3 lines) were investigated. The expression of connective tissue growth factor, CTGF, which is a key mediator in hyper-tropic scarring, and relative intensity of CTGF as a function of time were determined by western blot and gelatin Zymography. After injury (1 line), CTGF level was increased more than 2-fold within 1 h and continuously increased up to 3-fold at 6 h and was leveled down to reach normal value at 36 h, at which cell migration was complete. In more serious injury (2 lines), higher expression of CTGF was observed. The down regulation of CTGF expression after CTGF siRNA/lipofectamine transfection in control, 1 line and 2 lines scratch conditions were 40%, 75% and 55%, respectively. As a model anti-CTGF based therapy, CTGF siRNA with different ratios of linear polyethyleneimine (PEI) complexes (1:1, 1:5, 1:10, 1:20 and 1:30) were prepared and down-regulation efficacy of CTGF was evaluated with our optimized scratch assay, which is 1 line injury at 6 h post injury observation time. As the cationic linear PEI ratio increased, the down regulation efficacy was increased from 20% (1:20) to 55% (1:30). As CTGF level was increased to the highest at 6 h and leveled down afterwards, CTGF level at 6 h could provide the most sensitive response upon CTGF siRNA transfection. The scratch assay in the present study can be employed as a useful experimental tool to differentiate

  7. New targeted therapies such as anti-adhesion molecules, anti-IL-12/23 and anti-Janus kinases are looking toward a more effective treatment of inflammatory bowel disease.

    PubMed

    Bravatà, Ivana; Fiorino, Gionata; Allocca, Mariangela; Repici, Alessandro; Danese, Silvio

    2015-01-01

    Antitumor necrosis factor α agents have dramatically changed the management of inflammatory bowel disease (IBD). However, a significant proportion of patients does not respond or lose response over time. Hence, there is an urgent need for new molecules, with different mechanisms of action, and with a targeted and more effective approach. These new drugs include either small molecules or biological agents. We describe the three most promising classes of molecules in the field of IBD: anti-adhesion, anti-interleukin 12/23 and anti-Janus Kinases therapies. PMID:25523561

  8. Guidelines for the Topical Treatment of Psoriasis Vulgaris in the Levant and Iraq Area.

    PubMed

    Abbas, Ossama; Ammoury, Alfred; Abbadi, Mohammad; Malek, Medhat Abdel; Akkash, Laith; Al-Chakharah, Kamal; Al-Hamdi, Khalil; Al-Qarqaz, Firas; Al-Soudani, Abduljabbar; Al-Soudani, Nameer; Dandashle, Anwar; El-Sayed, Fouad; Ghafir, Yasser; Gargour, Nazek; Kabalan, Said; Kibbi, Abdul-Ghani; Oumeish, Isam; Tannous, Zeina; Tomb, Roland

    2015-01-01

    Psoriasis vulgaris is a common chronic, inflammatory, multisystem disorder that affects approximately 1.5% to 3.4% of the population in the Middle East. The disease has an impact on the quality of life in a significant number of affected patients. The majority of patients (approximately 70%) have mild to moderate psoriasis that is manageable with topical agents, which generally show a high efficacy to safety ratio. Topical agents can be used alone when treating patients with limited disease or may be used as adjunctive therapy for patients with more extensive psoriasis undergoing systemic treatment. Treatment should also be customized to meet individual patients' needs. To optimize the topical treatment of psoriasis in the Levant and Iraq area, dermatology experts from Iraq, Jordan, Lebanon, Palestine, and Syria met and initiated a project to develop guidelines and recommendations for the topical management of psoriasis. The guidelines are based on literature evidence and experts' opinions. We present recommendations for the use of topical corticosteroids, vitamin D analogues, calcineurin inhibitors, tazarotene, salicylic acid, anthralin, and coal tar, as well as combination therapy, based on their efficacy and safety profiles. PMID:26861521

  9. Positive effect of modified Goeckerman regimen on quality of life and psychosocial distress in moderate and severe psoriasis.

    PubMed

    Chern, Erick; Yau, Diana; Ho, Ji-Chen; Wu, Wei-Ming; Wang, Cheng-Yu; Chang, Hsueh-Wen; Cheng, Yu-Wen

    2011-06-01

    Psoriasis is a chronic inflammatory skin disease with a profound effect on quality of life and psychosocial stress. The relationship between clinical improvement and psycho-social impact after treatment is complex. The objective of this study was to compare changes in quality of life and psychosocial distress, and overall cost-effectiveness, in patients with psoriasis receiving the modified Goeckerman regimen (UV irradiation and coal tar) with those receiving conventional treatment. Patients with moderate/severe psoriasis receiving the Goeckerman regimen were followed from admission to discharge. Clinical severity, was evaluated weekly using the Psoriasis Area and Severity Index (PASI). Psoriasis Disability Index (PDI) and Hospital Anxiety and Depression Scale (HADS) questionnaires were applied at admission and one month after discharge. Thirty-six patients with psoriasis receiving conventional treatment and 48 patients receiving the Goeckerman regimen were recruited to the study. The mean PASI score in the Goeckerman group decreased from 27.1 to 6.9 and PDI scores decreased from 25.3 to 13.8. HADS scores for anxiety and depression decreased significantly from 9.8 to 6.3 and 9.1 to 6.8, respectively. In comparison with conventional therapy, the modified Goeckerman regime showed similar clinical efficacy, with additional benefits in improving overall quality of life and psychosocial distress in patients with moderate/severe psoriasis, and more cost-effectiveness. PMID:21537818

  10. Interleukin-17 inhibitors. A new era in treatment of psoriasis and other skin diseases

    PubMed Central

    Wasilewska, Agnieszka; Winiarska, Marta; Olszewska, Małgorzata

    2016-01-01

    Psoriasis is a chronic skin disease caused by the excessive secretion of inflammatory cytokines. Available therapeutic options include biologic drugs such as tumor necrosis factor alpha inhibitors and interleukin 12/23 (IL-12/23) inhibitors. The recent discovery of IL-17, which contributes to development of psoriasis, opened new possibilities for further treatment modalities. Currently, one anti-IL17 biological agent is approved for the treatment – a fully human monoclonal antibody that targets IL-17A (secukinumab). Further clinical trials, including a humanized IgG4 specific for IL-17 (ixekizumab) and a fully human antibody that targets the IL-17 receptor A (brodalumab). PMID:27605893

  11. Interleukin-17 inhibitors. A new era in treatment of psoriasis and other skin diseases.

    PubMed

    Wasilewska, Agnieszka; Winiarska, Marta; Olszewska, Małgorzata; Rudnicka, Lidia

    2016-08-01

    Psoriasis is a chronic skin disease caused by the excessive secretion of inflammatory cytokines. Available therapeutic options include biologic drugs such as tumor necrosis factor alpha inhibitors and interleukin 12/23 (IL-12/23) inhibitors. The recent discovery of IL-17, which contributes to development of psoriasis, opened new possibilities for further treatment modalities. Currently, one anti-IL17 biological agent is approved for the treatment - a fully human monoclonal antibody that targets IL-17A (secukinumab). Further clinical trials, including a humanized IgG4 specific for IL-17 (ixekizumab) and a fully human antibody that targets the IL-17 receptor A (brodalumab). PMID:27605893

  12. Anti-TNF therapy for juvenile idiopathic arthritis-related uveitis

    PubMed Central

    Semeraro, Francesco; Arcidiacono, Barbara; Nascimbeni, Giuseppe; Angi, Martina; Parolini, Barbara; Costagliola, Ciro

    2014-01-01

    Juvenile idiopathic arthritis-related uveitis is the most common type of uveitis in childhood and one of the main causes of visual impairment in children. The introduction of biological treatment has widened the range of therapeutic options for children with uveitis refractory to standard nonbiologic immunosuppressants. Data from clinical trials suggest that both adalimumab and infliximab have demonstrated effectiveness and safety in open-label studies, although no large, randomized, controlled trials have been reported so far. The role of etanercept in treating juvenile idiopathic arthritis-related uveitis is not yet well defined. In our experience, anti-tumor necrosis factor therapy has been shown to be more effective than steroids and/or methotrexate in treating uveitis. Up to now, tumor necrosis factor blocking compounds have been reserved for the treatment of the most severe cases of refractory uveitis, and larger prospective clinical trials are required in order to better assess the safety of these new compounds. PMID:24711694

  13. Viruses, anti-viral therapy, and viral vaccines in children with immune thrombocytopenia.

    PubMed

    Elalfy, Mohsen S; Nugent, Diane

    2016-04-01

    Immune thrombocytopenia (ITP) might be preceded by silent or overt viral infections. Similarly, anti-viral drugs and viral vaccines could also trigger ITP and might play a central role in its pathogenesis. The seasonal nature of childhood ITP suggests that viral infections might initiate immune responses that increase the predisposition and occurrence of ITP. Active cytomegalovirus or Epstein-Barr virus should be considered in differential diagnosis when thrombocytopenia is associated with lymphadenopathy, especially with splenomegaly. This review will focus on the specific association of ITP in association with viral disease and vaccinations, and will discuss the effectiveness of current therapies in light of our current understanding of viral-associated ITP. PMID:27312173

  14. Anti-tubercular therapy for intraocular tuberculosis: A systematic review and meta-analysis.

    PubMed

    Kee, Ae Ra; Gonzalez-Lopez, Julio J; Al-Hity, Aws; Gupta, Bhaskar; Lee, Cecilia S; Gunasekeran, Dinesh Visva; Jayabalan, Nirmal; Grant, Robert; Kon, Onn Min; Gupta, Vishali; Westcott, Mark; Pavesio, Carlos; Agrawal, Rupesh

    2016-01-01

    Intraocular tuberculosis remains a diagnostic and management conundrum for both ophthalmologists and pulmonologists. We analyze the efficacy and safety of anti-tubercular therapy (ATT) in patients with intraocular tuberculosis and factors associated with favorable outcome. Twenty-eight studies are included in this review, with a total of 1,917 patients. Nonrecurrence of inflammation was observed in pooled estimate of 84% of ATT-treated patients (95% CI 79-89). There was minimal difference in the outcome between patients treated with ATT alone (85% successful outcome; 95% CI 25-100) and those with concomitant systemic corticosteroid (82%; 95% CI 73-90). The use of ATT may be of benefit to patients with suspected intraocular tuberculosis; however, this conclusion is limited by the lack of control group analysis and standardized recruitment and treatment protocols. We propose further prospective studies to better establish the efficacy of ATT and ascertain the factors associated with favorable treatment outcomes. PMID:26970263

  15. The iatrogenic cost of non-steroidal anti-inflammatory drug therapy.

    PubMed

    De Pouvourville, G

    1995-04-01

    The secondary gastrointestinal effects associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs) are well documented in the medical literature. Less addressed is the 'iatrogenic' cost due to the treatment of these secondary effects. Epidemiologic and clinical studies report that the cost of NSAIDs is multiplied by a coefficient that ranges from 1.45 to 3, if the cost of treating the induced gastrointestinal complications is considered. A simple methodology incorporating the direct medical cost of treating complications has been developed to calculate a 'shadow price' of an NSAID, thus reflecting the real cost to the payer of NSAID therapy. The model has been used to compare three NSAIDs on the basis of their relative prices and gastroduodenal toxicity. PMID:7780675

  16. Cutaneous blood flow in psoriasis

    SciTech Connect

    Klemp, P.; Staberg, B.

    1983-12-01

    The disappearance rate of /sup 133/Xe was studied in 20 patients with psoriasis vulgaris, using an epicutaneous labeling technique in involved skin lesions or normal-appearing skin of the proximal extensor site of the forearm. Control experiments were performed in 10 normal subjects. Calculations of the cutaneous blood flow (CBF) in psoriatic skin lesions were performed using a tissue-to-blood partition coefficient for /sup 133/Xe, lambda c,pso, of 1.2 ml/100 g/min. lambda c,pso was estimated after the relative content of water, lipids, and proteins had been analyzed in psoriatic skin biopsies of 6 patients with untreated psoriasis. The mean relative content of water was markedly reduced to 23.5 +/- 1.5% (SEM), and lipids and proteins were markedly increased to 2.5 +/- 0.7% and 74.0 +/- 2.2, respectively, compared to previously published data for normal skin (water 72.5%, lipids 1%, proteins 26.5%). Mean CBF in untreated psoriatic skin was 63.5 +/- 9.0 ml/100 g/min. This was significantly higher than the mean CBF in 10 normal subjects, 6.3 +/- 0.5 ml/100 g/min (p much less than 0.0001). Mean CBF in normal-appearing skin in patients with psoriasis was 11.0 +/- 1.3 ml/100 g/min. This was significantly higher than CBF in normal subjects (p less than 0.0002).

  17. Conditional Cytotoxic Anti-HIV Gene Therapy for Selectable Cell Modification.

    PubMed

    Garg, Himanshu; Joshi, Anjali

    2016-05-01

    Gene therapy remains one of the potential strategies to achieve a cure for HIV infection. One of the major limitations of anti-HIV gene therapy concerns recovering an adequate number of modified cells to generate an HIV-proof immune system. Our study addresses this issue by developing a methodology that can mark conditional vector-transformed cells for selection and subsequently target HIV-infected cells for elimination by treatment with ganciclovir (GCV). We used the herpes simplex virus thymidine kinase (TK) mutant SR39, which is highly potent at killing cells at low GCV concentrations. This gene was cloned into a conditional HIV vector, pNL-GFPRRESA, which expresses the gene of interest as well as green fluorescent protein (GFP) in the presence of HIV Tat protein. We show here that TK-SR39 was more potent that wild-type TK (TK-WT) at eliminating infected cells at lower concentrations of GCV. As the vector expresses GFP in the presence of Tat, transient expression of Tat either by Tat RNA transfection or transduction by a nonintegrating lentiviral (NIL) vector marked the cells with GFP for selection. In cells selected by this strategy, TK-SR39 was more potent at limiting virus replication than TK-WT. Finally, in Jurkat cells modified and selected by this approach, infection with CXCR4-tropic Lai virus could be suppressed by treatment with GCV. GCV treatment limited the number of HIV-infected cells, virus production, as well as virus-induced cytopathic effects in this model. We provide proof of principle that TK-SR39 in a conditional HIV vector can provide a safe and effective anti-HIV strategy. PMID:26800572

  18. Closing faucets: the role of anti-angiogenic therapies in malignant pleural diseases.

    PubMed

    Marquez-Medina, D; Popat, S

    2016-08-01

    Malignant pleural effusion (MPE) represents 15-35 % of pleural effusions and markedly worsens the prognosis and quality of life of patients with cancer. Malignant mesothelioma (MM) and lung adenocarcinoma are the most frequent primary and secondary causes, respectively, of MPE. Effective treatments for cancer-related MPE are warranted in order to improve symptoms, reduce the number of invasive pleural procedures, and prolong patient life. Since angiogenesis plays a key role in MPE development, the potential role of bevacizumab and other anti-angiogenic therapies have been explored in this review. No relevant phase III trials have specifically analysed the benefit from adding bevacizumab to platinum-based chemotherapy in lung cancer-related MPE. However, small retrospective series reported 71.4-93.3 % MPE control rate, a reduction in invasive procedures, and a safe profile with this combination. Being approved for the first-line treatment of non-squamous advanced NSCLC, the addition of bevacizumab should be considered for patients presenting with MPE. In addition, further studies in this are recommended. In MM, the addition of bevacizumab to platinum-based chemotherapy did not meet primary endpoints in two phase II trials. However, the beneficial results on OS reported in comparison with historical cohorts and the statistically significant benefit on PFS and OS observed in the phase III MAPS trial foretell an eventual role for the combination of platinum/pemetrexed/bevacizumab as front-line systemic therapy for pleural MM. To date, no other anti-angiogenic drug has showed significant benefit in the treatment of patients with either MPE or MM. However, new promising drugs such as ramucirumab or recombinant human endostar warrant further investigation. PMID:26680633

  19. Natural products as starting points for future anti-malarial therapies: going back to our roots?

    PubMed Central

    2011-01-01

    Background The discovery and development of new anti-malarials are at a crossroads. Fixed dose artemisinin combination therapy is now being used to treat a hundred million children each year, with a cost as low as 30 cents per child, with cure rates of over 95%. However, as with all anti-infective strategies, this triumph brings with it the seeds of its own downfall, the emergence of resistance. It takes ten years to develop a new medicine. New classes of medicines to combat malaria, as a result of infection by Plasmodium falciparum and Plasmodium vivax are urgently needed. Results Natural product scaffolds have been the basis of the majority of current anti-malarial medicines. Molecules such as quinine, lapachol and artemisinin were originally isolated from herbal medicinal products. After improvement with medicinal chemistry and formulation technologies, and combination with other active ingredients, they now make up the current armamentarium of medicines. In recent years advances in screening technologies have allowed testing of millions of compounds from pharmaceutical diversity for anti-malarial activity in cellular assays. These initiatives have resulted in thousands of new sub-micromolar active compounds – starting points for new drug discovery programmes. Against this backdrop, the paucity of potent natural products identified has been disappointing. Now is a good time to reflect on the current approach to screening herbal medicinal products and suggest revisions. Nearly sixty years ago, the Chinese doctor Chen Guofu, suggested natural products should be approached by dao-xing-ni-shi or ‘acting in the reversed order’, starting with observational clinical studies. Natural products based on herbal remedies are in use in the community, and have the potential unique advantage that clinical observational data exist, or can be generated. The first step should be the confirmation and definition of the clinical activity of herbal medicinal products already

  20. Role of anti-angiogenesis therapy in the management of hepatocellular carcinoma: The jury is still out

    PubMed Central

    Sun, Hong; Zhu, Man-Sheng; Wu, Wen-Rui; Shi, Xiang-De; Xu, Lei-Bo

    2014-01-01

    As the leading cause of disease-related deaths, cancer is a major public health threat worldwide. Surgical resection is still the first-line therapy for patients with early-stage cancers. However, postoperative relapse and metastasis remain the cause of 90% of deaths of patients with solid organ malignancies, including hepatocellular carcinoma (HCC). With the rapid development of molecular biology techniques in recent years, molecularly targeted therapies using monoclonal antibodies, small molecules, and vaccines have become a milestone in cancer therapeutic by significantly improving the survival of cancer patients, and have opened a window of hope for patients with advanced cancer. Hypervascularization is a major characteristic of HCC. It has been reported that anti-angiogenic treatments, which inhibit blood vessel formation, are highly effective for treating HCC. However, the efficacy and safety of anti-angiogenesis therapies remain controversial. Sorafenib is an oral multikinase inhibitor with anti-proliferative and anti-angiogenic effects and is the first molecular target drug approved for the treatment of advanced HCC. While sorafenib has shown promising therapeutic effects, substantial evidence of primary and acquired resistance to sorafenib has been reported. Numerous clinical trials have been conducted to evaluate a large number of molecularly targeted drugs for treating HCC, but most drugs exhibited less efficacy and/or higher toxicity compared to sorafenib. Therefore, understanding the mechanism(s) underlying sorafenib resistance of cancer cells is highlighted for efficiently treating HCC. This concise review aims to provide an overview of anti-angiogenesis therapy in the management of HCC and to discuss the common mechanisms of resistance to anti-angiogenesis therapies. PMID:25544869