Inflammation & allergy drug targets最新文献

Sarcoidosis is a systemic, granulomatous disease that can affect multiple organs and has a variable clinical course. Corticosteroids (e.g. prednisone) remain the mainstay of therapy in sarcoidosis since their first use in this disease in the 1950s. A second-line therapeutic is often added to the treatment regimen in case of intolerable side effects, inefficacy or prolonged use of steroids. Methotrexate is considered by many to be the first choice drug in second-line therapeutics of sarcoidosis. Other often used second-line drugs are azathioprine and leflunomide. No large trials comparing different treatment options have been performed in sarcoidosis. In patients with severe disease who do not respond well to first and second-line therapy, biologicals such as infliximab can be promising. In this review, we provide a complete overview of all currently available therapeutic strategies in sarcoidosis. In addition, the gaps in current literature on sarcoidosis treatment were depicted to underline the importance of research in this mostly empiric field of medicine. Furthermore we highlight future medicine in sarcoidosis with emphasis on the role of personalised medicine.

Herbal medicine has a long background equal to history of humankind. Several plants have been used as remedies in ancient Persian, Egyptian, Chinese and Indian civilizations. The plant Ocimum sanctum Linn. (Tulsi) is one of these medicinal plants with a wide variety of applications in traditional medicine. In modern era, it has been shown to be effective against diabetes mellitus, hypertension, cancers, bronchitis, and found to have anti-microbial properties. Several experimental studies have confirmed its anti-inflammatory properties and its role in modulation of both cellular and humeral immunity. Recently its efficacy against inflammatory response, hepatic injury and gastric ulcer has been elucidated in animal studies. In liver, essential oils and extracts of Ocimum sanctum could prevent oxidative stress by increasing glutathione peroxidae and catalase and were also effective in prevention of hepatic steatosis. In gastric epithelial tissue different derivatives of Ocimum sanctum had anti-ulcer and anti-secretory characteristics and could heal gastric ulceration. These beneficial properties of this medicinal plant can mainly originate from its major biochemically active constituents like eugenol, carvacrol, ursolic acid, β-caryophyllene and rosmarinic acid. Here in, we reviewed current literature about anti-inflammatory, gastric and hepatoprotective properties of Ocimum sanctum.

Background: Recent studies have shown that psoriasis is associated with risk factors for cardiovascular diseases (CVDs).

Objectives: To evaluate the epidemiological profile of patients with psoriasis, focusing on the risk factors for CVDs and inflammation.

Materials & methods: Patients with a diagnosis of psoriasis who were attended at the dermatology outpatient clinic of a university hospital were evaluated.

Results: 229 adult patients of mean age 50 years, among whom 52% were male, were evaluated. Twenty patients (8.7%) were concomitantly affected by psoriatic arthritis. From analysis on laboratory tests from 177 patients, we saw that 111 (62.7%) were dyslipidemic and that among these, only 9 (8%) were undergoing treatment. 35.6% presented abnormal glycemia tests, but 22% were not having any treatment for the glycemic alteration observed. We analyzed possible associations of the severity of psoriasis and length of time with the disease with lipid disorders, glycemic disorders and systemic arterial hypertension, but did not find any significant associations.

Conclusion: The findings observed in this study corroborate previous findings in similar studies, thus demonstrating that the prevalence of risk factors for CVDs among patients with psoriasis is greater than in the general population, but that a large proportion of such patients do not undergo treatment for this. We did not find any possible association between the inflammatory process and the genesis of risk factors for CVDs, although the magnitude of this evidence is not strong. These findings serve to alert dermatologists to remain attentive to these factors, among patients with psoriasis.

Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen, which is the major cause of severe chronic lung infection in cystic fibrosis patients. It is also responsible for systemic infections in immunocompromised individuals and those presenting with significant pulmonary conditions in intensive care units. This microorganism has the capacity to initiate severe inflammation in infected lungs resulting in detrimental tissue damage. We have hypothesized that Syk protein tyrosine kinase mediates lung epithelial cellular responses to P. aeruginosa infection, and that a naturally occurring non-toxic Syk inhibitor piceatannol can protect infected human cells against the deleterious effects associated with this infection. We infected Syk-positive H292 or Syk-negative A549 human lung epithelial cell lines with P. aeruginosa and assessed the resulting cellular responses, i.e. production of proinflammatory cytokines, adhesion molecule expression, generation of reactive oxygen species, and apoptosis of infected cells, utilizing a multiplex bead-based immunoassay and flow cytometry. We also studied the internalization of P. aeruginosa using the gentamicin exclusion assay. We found that the piceatannol treatment significantly suppressed inflammation, oxidative stress and apoptosis in H292, but not in A549 cells implicating Syk participation in the regulation of the pathological processes induced by P. aeruginosa infection. Intriguingly, piceatannol was able to down-regulate the internalization of P. aeruginosa by both Syk-positive and Syk-negative cell lines, implying that the mechanisms of action of this compound extend beyond Syk inhibition. As piceatannol can interfere with several mechanisms of bacterial pathogenesis this natural compound deserves further study as a potential therapeutic option in P. aeruginosa infection.

Introduction: The cardiovascular magnetic resonance (CMR) pattern of Churg-Strauss syndrome (CSS) includes myopericarditis, diffuse subendocardial vasculitis or myocardial infarction with or without cardiac symptoms and is usually associated with lack of antineutrophil cytoplasmic antibodies (ANCA).

Aim: To correlate the CMR pattern with ANCA in CSS, compare it with healthy controls and systemic lupus erythematosus (SLE) patients and re-evaluate 2 yrs after the first CMR.

Patients-methods: 28 consecutive CSS, aged 42±7 yrs, were referred for CMR and 2 yrs re-evaluation. The CMR included left ventricular ejection fraction (LVEF), T2-weighted (T2-W), early (EGE) and late gadolinium enhanced (LGE) imaging. Their results were compared with 28 systemic lupus erythematosus (SLE) under remission and 28 controls with normal myocardial perfusion, assessed by scintigraphy.

Results: CMR revealed acute cardiac lesions in all ANCA (-) CSS with active disease and acute cardiac symptoms and only in one asymptomatic ANCA (+) CSS, with active disease. Diffuse subendocardial fibrosis (DSF) or past myocarditis was identified in both ANCA(+) and ANCA (-) CSS, but with higher incidence and fibrosis amount in ANCA (-) CSS (p<0.05). In comparison to SLE, both ANCA (+) and ANCA (-) CSS had higher incidence of DSF, lower incidence of myocarditis and no evidence of myocardial infarction, due to coronary artery disease (p<0.05). In 2 yrs CMR follow up, 1/3 of CSS with DSF presented LV function deterioration and one died, although immunosuppressive treatment was given early after CSS diagnosis.

Conclusions: Cardiac involvement either as DSF or myocarditis, can be detected in both ANCA (+) and ANCA (-) CSS, although more clinically overt in ANCA (-). DSF carries an ominous prognosis for LV function. CMR, due to its capability to detect disease severity, before cardiac dysfunction takes place, is an excellent tool for CSS risk stratification and treatment individualization.

Accumulating evidence suggests that Green tea polyphenolic catechins, especially the (-)-epigallocatechin gallate (EGCG), can be cross-linked to many proteins, and confer a wide range of anti-bacterial activities possibly by damaging microbial cytoplasmic lipids and proteins. At the doses that conferred protection against lethal polymicrobial infection (induced by cecal ligation and puncture), EGCG significantly reduced bacterial loads particularly in the liver and lung. To elucidate its bactericidal mechanisms, we determined whether EGCG affected the fluorescence intensities of bacteria-conjugated Alexa Fluor 488 or 594 dyes. When mixed with unconjugated Alexa Fluor 488 or 594 dyes, EGCG or analogs did not affect the fluorescence intensity of these dyes. In a sharp contrast, EGCG and some analogs (e.g., Catechin Gallate, CG), markedly reduced the fluorescence intensity of Gram-positive Staphylococcus aureus-conjugated Alexa 594 and Gram-negative Escherichia coli-conjugated Alexa 488. Interestingly, co-treatment with ethanol impaired the EGCG-mediated fluorescence quenching of the G(+) S. aureus, but not of the G(-) E. coli-conjugated Alexa Flour dyes. In light of the notion that Alexa Fluor dyes can be quenched by aromatic amino acids, it is plausible that EGCG exerts antimicrobial activities possibly by altering microbial protein conformations and functions. This possibility can now be explored by screening other fluorescence-quenching agents for possible antimicrobial activities.

The association between autoimmune rheumatic diseases and obstructive sleep apnea (OSA) is complex. Systemic inflammation secondary to OSA may underlie this association. It is possible that OSA-related inflammation may trigger the occurrence of autoimmune rheumatic disease in genetically susceptible individuals. On the other hand, autoimmune rheumatic diseases can lead to OSA or worsen preexisting OSA. Temporomandibular joint destruction, cervical spine subluxation and brainstem compression are the factors responsible for the above observation. Future studies are needed to clarify whether OSA is an independent risk factor for the development of autoimmune disease and whether OSA management will lead to a reduction in the incidence of autoimmune disease. On the other hand, it is important to treat autoimmune rheumatic disease promptly, to reduce the risk of complications, with OSA being one of these.

Several studies describing the "natural history" of Peyronie's disease (PD) (Chronic Inflammation of the Tunica Albuginea-CITA) showed that untreated patients with PD seem to have spontaneous improvement. Because of these articles many physicians found to have a non-therapeutic behavior in case of PD. This paper tries to define the natural history of PD using penile dynamic duplex ultrasound evaluation in function of factors able to elicit fibrosis of the penis. Eighty-two patients have been studied, the mean time being between PD onset and diagnosis was 9.6 ± 3.8 months, mean age was 52.6 ± 10.69. Each patient underwent to two clinical assessments for PD, with a time-lag of 18.08 ± 9.2 months. Each assessment comprises: measurement of: plaque volume in cm(3) (with dynamic echocolor Doppler ultrasonography), penile curvature in degrees (with Kelami method), pain (with Pain Intensity Numerical Rating Scale/PINRS) and sexual function (with IIEF15 scale). The following clinical and laboratory assessments were carried out on each patient: body-mass index (BMI), blood pressure measurement, blood count, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, blood sugar, glycated haemoglobin and total testosterone. We assessed whether PD plaque volume, penile deformity, pain and modify by time, in function of risk factors of fibrosis (aging, smoking habit, erectile failure, number of comorbidities, BMI, radical prostatectomy) and/or of the severity of symptoms (plaque area, penile deformity and calcifications). Qualitative-quantitative non parametric multivariate analysis has been used as statistical test. The analysis indicated that PD symptoms increase by time in the majority of the patients, and that the increase is not linked to the severity of symptoms, but to the risk factors for developing fibrosis, with the exception of age that is inversely related. PD is a progressive disease, whose progression is linked to young age and to risk factors of fibrosis.

Inflammation is viewed as one of the major causes for the development of different diseases like cancer, cardiovascular disease, diabetes, obesity, osteoporosis, rheumatoid arthritis, inflammatory bowel disease, asthma, and CNS related diseases such as depression and parkinson's disease; and this fervent phenomenon provides space for understanding different inflammatory markers. Increasing evidences have elucidated the outcome of inflammatory pathways dysregulation resulting in many symptoms of chronic diseases. The detection of transcription factors such as nuclear factor kappa-B (NF-κB), STAT and their gene products such as COX-2, cytokines, chemokines and chemokine receptors has laid molecular foundation for the important role of inflammation in chronic diseases in which the NF-κB is reported as a major mediator which makes a possible way for the development of new therapeutic approaches using synthetic and natural compounds that might eventually decrease the prevalence of these diseases. Even if many inflammatory markers like TNF-α, IL-1, IL-6, IL-8 and C-reactive protein (CRP) are reported to be the major key factors with proved role in several inflammatory diseases, IL-1 and TNF-α are the important cytokines that can induce the expression of NF-κB which is the potential target in these inflammatory diseases. This review aims to explore and summarize that how some drugs and natural compounds show their modulatory activity in inflammatory pathways and chronic inflammatory markers in these inflammatory diseases.

Novel carrier-linked azo prodrugs of 4 and 5-aminosalicylic acids (4-ASA and 5-ASA respectively) using the same drugs as carriers in different permutations and combinations were designed for targeting colon affected with inflammatory bowel disease (IBD). Improved hydrophilic nature of the prodrugs assisted in minimizing their absorption in upper GIT and efficient delivery of the active drugs to colon as evidenced from their stability in aqueous buffers (pH 1.2 and 7.4) and upper GIT homogenates with 68-91% release on incubation with rat cecal matter. Amongst the series, 4A4AAZ (prodrug of 4-ASA with 4-ASA) at a dose of 53 mg/Kg was found to be the most promising candidate as it substantially alleviated the quantifying markers of colonic inflammation in TNBS-induced experimental colitis in Wistar rats. Moreover it displayed significantly lower GI toxicity (at ten times higher dose). 5-ASA- induced pancreatitis and sulfapyridine-induced adverse effects on liver that are characteristic of sulfasalazine were not observed with 4A4AAZ. It could be explored further as a potential candidate for IBD patients intolerant to pancreatitis induced by oral administration of 5-ASA.