Recent Patents on Inflammation & Allergy Drug Discovery - Volume 8, Issue 3, 2014

There are numerous studies in the literature regarding the involvement of intestinal as well as extra intestinal organs during the course of celiac disease, and there is accumulating evidence regarding the pancreatic changes caused by this pathology. Method: The literature on the relationship between celiac disease and pancreatic involvement has been extensively reviewed. Results: Exocrine pancreatic involvement regards both the function and the morphology of the exocrine pancreas, and superimposed or more severe clinical changes seem to be related to the nutritional disturbances caused by celiac disease or by the disease itself. Patients with celiac disease may also develop a chronic pancreatitis more frequently than in general population both the intestinal and the extraintestinal manifestations of celiac disease. Conclusions: Fecal elastase 1-determination in celiacs may be useful in detecting and curing exocrine pancreatic insufficiency especially in patients with a new diagnosis of celiac disease or in those with refractory diarrhea. Few patents on pancreatic extracts are also briefly described.

Allergic diseases are common worldwide and are prevalently caused by an inflammatory pathophysiology induced by the exposure to the specific allergen(s). The development of inflammation requires the involvement of regulatory cells that include antigen presenting cells and T lymphocytes, respectively orientating and orchestrating the immunological response, and the activity of cells such as mast cells and basophils, that release the typical mediators of allergic reactions, and eosinophils, which sustain the protracted inflammation. Differently from other sites of contact with allergen( s) such as respiratory or gastrointestinal tissues, the oral mucosa, based on the abundance of dendritic cells and their interaction with T cells, apparently works as a tolerogenic site concerning the response to allergen molecules. The other pivotal aspect of the oral mucosa is the minimal presence of inflammatory cells, especially eosinophils and mast cells. These characteristics play a crucial role in the sublingual administration of allergen immunotherapy, which in fact is easier to tolerate than injective immunotherapy, taking into account recent studies highlighting the important role of the Waldeyer's ring in developing tolerance to the sublingually administered allergen. Some patents addressing the identification of therapeutic agents for allergic inflammation are also summarized.

Allergic reactions can cause by several aliments and foods. Symptoms usually appear after ingestion, several hours after consumption or even almost immediately. Various food allergies can lead to serious diseases and in some cases to death, so the priority for people suffering from them should be prevention and completely avoiding foods that cause this kind of reactions. Allergy to Alioidea is one of the probable causes of contact dermatitis, gingival and oculonasal diseases and asthma. In this review, we will focus on the increasing incidence of allergy to foods of common use like onions and garlic. In the last ten years, the world production of onions and garlic has increased of at least 25%. People make large use of them, not only in cookery but also from a therapeutic point of view. Their growing use is producing more and more specific, insidious and sometimes serious medical conditions, which highly influence the quality of life of patients. Medical practitioners should be able to recognize immediately these disorders in order to diagnose them quickly and accurately, avoiding unnecessary tests and treatments. We will also describe new patents for detecting food allergens.

Hepatic encephalopathy is a brain functional disorder, characterized by neuropsychiatric abnormalities with liver failure. High blood ammonia, causing glutamate neurotoxicity is the basic cause, finally leading to low-grade cerebral edema. Its manifestation is more likely in patients of sepsis, oxidative stress, generalized inflammation, gut mal-functioning, amoebiaesis, viral hepatitis, nervous imbalance, etc. Thus, the therapeutic goals primarily include the maintenance of proper blood supply and prevention of hypoxic condition in liver, along with management of factors responsible for high blood ammonia, oxidative stress, inflammation, and high GI- serotonin. The drugs in clinical practice include lactulose, sodium benzoate, flumazenil and rifaximin, supplementation of zinc, branched chain amino acids (BCAA), l-ornithine-l aspartate, antioxidants and iNOS inhibitors. However, herbal formulations would be of great importance as it shows multi-targeted action because it possesses a natural cocktail of secondary metabolites. It can collectively act as an antioxidant, anti-inflammatory, prebiotic, hepatoprotective and neuron-protective agents. We have briefly outlined some of these plants and also recent patents useful in the management of hepatic encephalopathy.

The term “Glaucoma” is used to describe a number of diseases of the eye characterized by a particular form of optic nerve damage that is often associated with high intraocular pressure (IOP). The open-angle glaucoma is the most common form that is also referred to as chronic glaucoma. This is described as an optic neuropathy with multifactorial nature in which there is a loss of characteristics of the optic nerve fibers. Therapeutic options for the treatment of this disease are different, you can take advantage of eye drops, laser therapy and conventional surgery or more combined treatments. Medicated eye drops are the most common way to treat glaucoma. Although eye drops are widely used, adverse reactions are not frequently observed and described. In particular, the adverse skin reactions are not frequently described in the literature, but often seen in dermatologic clinic, we reported their skin reactions and possible alternative treatments described in literature and their patent applications.

Objective: BYSH, a herbal formula, was evaluated for efficacy and safety in a pilot study for patients with advanced hormone refractory prostate cancer (HRPC). Patients and Methods: The pilot study was designed as a singlecenter open-label trial. Patients with HRPC were treated with BYSH for 24 weeks. The primary end point was the changes in serum prostate-specific antigen (PSA) level. Safety parameters such as liver and renal functions were monitored during the study period. Results: Ten patients were eligible for the study. Most of them had stable PSA levels while taking BYSH. However, at the end of the BYSH treatment, the level of PSA increased. The median survival from diagnosis of HRPC was 16.4 months. Liver and renal functions remained normal. BYSH was well tolerated and no patient reported adverse events during the study period. Conclusion: Although it is inappropriate to make a conclusion based on the pilot study results, the trend of improvement is obvious. Further investigations should be conducted to demonstrate its clinical benefits. We have also briefly reviewed some plant products which are patented and also available in market.

Exposure to air pollutants can lead to lung inflammatory responses such as allergic asthma. Serotonin elevation is shown to be present in peripheral blood of symptomatic asthmatic patients. In this study, two genes, 5HTR2a and MAO-A playing important roles in serotonin function, were analyzed in peripheral blood mononuclear cells (PBMCs) of individuals who had been exposed to air pollution and allergic asthmatic patients as well. Thus, cDNA was synthesized from PBMCs’ mRNA of the subjects and then gene expression was measured by real-time PCR. 5HTR2A gene expression in PBMCs of both exposed individuals and allergic asthmatic patients was significantly increased compared with control group, whereas MAO-A gene expression showed no significant changes in neither groups. These results indicate that there may be association between increased 5HTR2a gene expression and exposure to air pollution as well as asthma incidence. Some relevant patents are also outlined in this article.

There are contradictory reports about the efficacy of minocycline for treating schizophrenia. This is a randomized, placebo-controlled clinical trial investigating the effectiveness of minocycline for treating schizophrenia. Forty three patients with schizophrenia diagnosed according to DSM-IV were randomly allocated into minocycline (200mg/d) + risperidone group (n = 21) or placebo + risperidone group (n = 22). Scale for Assessment of Negative Symptoms (SANS), Positive and Negative Syndrome Scale for schizophrenia (PANSS), Beck’s Depression inventory, and Abnormal Involuntary Movement Scale (AIMS) were used. Assessments occurred at baseline, week 4 and week 8. Thirty five patients completed the trial. The changes of SANS total score from baseline to week 4 were not statistically different between the two groups. However, at week 8, there was a statistically significant difference between the two groups. SANS score decreased in the minocycline group more than that of the placebo group (12.2(7.9) versus 6.8(8.6), respectively). The decline of PANSS Negative score from baseline to week 8 in the minocycline group was more than placebo group (4.3(4.2) versus 3.2(3.3). However, the difference was not statistically significant. No one dropped out due to adverse effects. This trial supports the effectiveness of minocycline as an adjuvant treatment with risperidone for treating negative symptoms of patients with schizophrenia. Some patents on the use of tetracycline for the treatment of schizophrenia are also outlined.

Aim: The authors aimed to show the possible relationship between keratoconjunctivitis sicca (KCS) and Chlamydia pneumonia from the point of view of clinical and microbiological diagnostics. Material and Methods: 94 adult patients were treated for follicular conjunctivitis with symptoms of KCS with possible Chlamydia pneumoniae etiology. The diagnosis of a chlamydial infection is based on the serological positivity of chlamydia antibodies and is further based on the antigen positivity in conjunctival imprint preparations. Patients were treated with azithromycin for a period of 12 days. Results: The reciprocal relationship between chlamydial infection and ocular symptoms was proved at 21 patients (22%). Ninety% of patients showed positive anti-Chlamydia pneumoniae IgA and/or IgM with positivity in 80%, including anti-LSP IgA and/or IgM antibodies. This finding was in correlation with the medium to strongly positive finding of anti-cHSP60 IgG. In two patients, this infection was confirmed by the positivity of Chlamydia pneumoniae DNA in peripheral leucocytes. The test group (100 healthy persons) showed 69% negative finding of anti-Chlamydia pneumoniae antibodies or only positive anamnestic antibodies (IgG) and 31% positive antibodies IgA or IgM without clinical sings. Conclusion: This study indicated the possible relationship between KCS and Chlamydia pneumoniae in the course of simultaneous clinical signs of follicular conjunctivitis. KCS is a consequence of the action of local infection at the surface of the conjunctiva. It also indicated the necessity of simultaneous evaluation of microbiological findings and the clinical picture in consideration of overall antibiotic treatment in view of the high antibody background of Chlamydia pneumoniae in the adult population in the Czech Republic. The authors aimed to show the possible relationship between the keratoconjunctivitis sicca and Chlamydia pneumoniae based on results of the two studies. Some patents on conjunctivitis are also briefly described in this article.