Inflammation & Allergy-Drug Targets (v.12, #6)

Current Therapy in Sarcoidosis, the Role of Existing Drugs and Future Medicine by Adriane D.M. Vorselaars, Coline H.M. van Moorsel, Vera H.M. Deneer, Jan C. Grutters (369-377).
Sarcoidosis is a systemic, granulomatous disease that can affect multiple organs and has a variable clinicalcourse. Corticosteroids (e.g. prednisone) remain the mainstay of therapy in sarcoidosis since their first use in this diseasein 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-linetherapeutics of sarcoidosis. Other often used second-line drugs are azathioprine and leflunomide. No large trialscomparing different treatment options have been performed in sarcoidosis. In patients with severe disease who do notrespond 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 mostlyempiric field of medicine. Furthermore we highlight future medicine in sarcoidosis with emphasis on the role ofpersonalised medicine.

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

Risk Factors for Cardiovascular Disease in Psoriasis: Relation to Inflammation Assessed by the Severity and Duration of Illness by Andrea Bronhara Pelá Calamita, Zamir Calamita, João Carlos Ferreira Braga (385-390).
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 andinflammation.;Materials & Methods: Patients with a diagnosis of psoriasis who were attended at the dermatology outpatient clinic of auniversity 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 abnormalglycemia tests, but 22% were not having any treatment for the glycemic alteration observed. We analyzed possibleassociations of the severity of psoriasis and length of time with the disease with lipid disorders, glycemic disorders andsystemic arterial hypertension, but did not find any significant associations.;Conclusion: The findings observed in this study corroborate previous findings in similar studies, thus demonstrating thatthe prevalence of risk factors for CVDs among patients with psoriasis is greater than in the general population, but that alarge proportion of such patients do not undergo treatment for this. We did not find any possible association between theinflammatory 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.

Diagnostic and Prognostic Potential of the Macrophage Specific Receptor CD163 in Inflammatory Diseases by Christa Buechler, Kristina Eisinger, Sabrina Krautbauer (391-402).
CD163 is a scavenger receptor for the endocytosis of hemoglobin and hemoglobin/haptoglobin complexes andis nearly exclusively expressed on monocytes and macrophages. CD163 is induced by IL-10 and glucocorticoids whileproinflammatory cytokines like TNF reduce its expression. The cytokine IL-6 which exerts pro- and anti-inflammatoryeffects depending on the signaling pathway activated strongly upregulates CD163. Anti-inflammatory cells involved inthe down-modulation of inflammation express high CD163 which controls immune response. Ligands of the toll-likereceptors 2, 4 and 5 stimulate ectodomain shedding of CD163 thereby releasing soluble CD163 (sCD163) which mediatescellular uptake of free hemoglobin. Soluble CD163 circulates in blood and is increased in serum of critically ill patients,in chronic inflammatory and infectious diseases. Serum concentrations of sCD163 are related to disease severity and aresuitable biomarkers for diagnosis, prognosis and therapeutic drug monitoring in several inflammatory disorders. RaisedsCD163 even predicts comorbidity and mortality in some diseases. Relationship of CD163/sCD163 and disease severitydemonstrates a fundamental role of monocytes/macrophages in various diseases. CD163 is a target to specifically deliverdrugs to macrophages intending advanced therapeutic efficiency and minimization of adverse reactions. In this reviewarticle factors regulating CD163 expression and shedding, current knowledge on the function of CD163 and sCD163, andinflammatory diseases where CD163 and/or sCD163 are mostly increased are summarized.

Objective: to demonstrate the possible effectiveness of a long-term multimodal medical therapy in patients withPeyronie's disease (PD) we carried out a controlled study on 82 patients diagnosed with PD, whereas in the scientificliterature the conservative treatment of this disease is much discussed.;Methods: 82 patients (mean age=53.6±10.1 years-range 23-68) diagnosed with PD were selected for this study. Of these41 patients (group A) were treated for 18 months as follows: Verapamil penile injections (12 total injections for sixmonths and subsequently every month for twelve months: total 24 injections) + Iontophoresis with Verapamil/daily +blueberries 160mg/daily + propolis 600mg/daily + Vitamin E 600mg/daily + topical Diclofenac/daily. The other 41patients spontaneously decided not to receive treatment for several motives and then were introduced as a control group B.All patients were controlled at 6- and 18-month follow up with the same diagnostic tests completed before the therapy(penile ultrasound, photograph documentation, pain scale etc.).;Results: In group A, after treatment of 6 and 18 months, the change in plaque volume consisted in volume reduction= -47.6% and -73.6% respectively, while in group B, the change consisted of an increase in plaque volume= +55.7% and+118.7% respectively (p=0.000). In group A, after treatment of 6 and 18 months, improvement of curvature occurred in76.3% and 81.5% of the cases respectively, while in group B it occurred in 2.7% and 8.1%, respectively (p<0.0001).;Conclusion: Our results showed that a long-term multimodal medical therapy (Verapamil associated with Antioxidantsand local Diclofenac) is statistically effective to treat PD patients, if we consider that lower therapeutic outcomes wereachieved after 6 months treatment (medium-term treatment). Furthermore, this study confirms that the best treatmentmodality for PD is a combination therapy.

Impact of Altered Early Infant Gut Microbiota Following Breastfeeding and Delivery Mode on Allergic Diseases by Abbas Ali Imani Fooladi, Soghra Khani, Hamideh Mahmoodzadeh Hosseini, Seyed Fazlollah Mousavi, Elnaz Mehdizadeh Aghdam, Mohammad Reza Nourani (410-418).
The prevalence of allergic diseases among infants is increasing particularly in developed countries. Although,the exact reason is not clear yet, one of the most probable explanations is reducing microbial exposure during early lifeand consequent alteration of gut microbiota. Various factors including delivery mode, infant`s diet, environment andantibiotics administration by mothers are involved in microbial colonization of infant`s intestine. Since the content ofinfant`gut microbiota plays a critical role in the maturation and development of the immune system, it determines the riskof immune diseases. Different studies confirmed the important role of vaginal delivery, due to transferring of usefulbacteria to the neonatal's intestine, and breastfeeding, owing to the presence of exosomes and different kind of mediatorsin the milk which modify the pattern of intestinal microflora. As a result, it was proposed that both factors haveremarkable effects on reducing allergic diseases. Furthermore, the consumption of probiotic productions by the motherduring and after pregnancy possibly induces beneficial impacts on attenuating the allergic diseases.

Azo prodrugs of aminosalicylates viz: 5-aminosalicylic acid and 4-aminosalicylic acid were synthesised usingphenols as colon- targeting carriers for management of inflammatory bowel disease. The structures were confirmed byspectral and elemental analysis. These azo- linked prodrugs showed increased hydrophilicity which prevented theirabsorption from the upper GIT thus delivering them intact to the colon. They were also seen to be stable in stomach andintestinal homogenates, showing minimal release. Activation of prodrugs was faster in cecal matter showing upto 96-98%release with prolonged half lives. Amongst the azo series; 5-A? and 4-Ares significantly attenuated the symptoms ofcolitis induced by TNBS but their overall efficacy was less than SLZ. Safety assessment revealed absence of anyabnormalities in hepatic and pancreas morphology with significantly low ulcerogenic propensity.

Investigation of 5-HT3A Receptor Gene Expression in Peripheral Blood Mononuclear Cells of Individuals who had been Exposed to Air Pollution by Ghasem Ahangari, Leila Mohammadi Amirabad, Sona Mozafari, Ali Majeidi, Gholamreza Derkhshan Deilami (433-438).
The role of air pollution in exacerbation of allergic symptoms is well known. Several studies have shown theeffect of air pollution on serotonergic system. The changes in serotonergic system could trigger several allergicsymptoms. 5-HT3A is among serotonin receptors on the peripheral Blood Mononuclear Cells (PBMCs) as well as othercells.;In the present study we compared the 5-HT3A gene expression in PBMCs of the asthmatic patients as well as individualswho had been exposed to the air pollution. Normal individuals were also included in the study as control for comparisonof 5-HT3A gene expression. Following the synthesis of the cDNA using mRNA extracted from PBMCs the level of 5-HT3A gene expression was measured using real-time PCR. The results showed t a significant increase in the relativeexpression level of 5-HT3A receptor in PBMCs from asthmatic patients and individuals exposed to the air pollutantscompared to normal controls. Our result indicates that significant increase in 5-HT3A receptor may contribute to thepathogenesis as well as allergic symptoms which resulted from air pollution.