Cannabinoids, loratadine and allopurinol as novel additions to the antipsoriatic ammunition

As the current antipsoriatic medications are commonly associated with deleterious side-effects, a determined search for safer agents, which could be used alone or in combination with current antipsoriatic drugs, would be very imperative. Psoriasis is believed to be characterized by a type 1 cytokine pattern; interferon-gamma, interleukin (IL)-2 and tumour necrosis factor (TNF)-alpha are predominantly expressed in this disorder. Nitric oxide, reactive oxygen species, histamine, leukotriene B4, and decreased [corrected] keratinocyte cyclic adenosine monophosphate/cyclic guanosine monophosphate (cAMP/cGMP) ratio are supposed to play roles in the pathogenesis of this disorder. Based on the immunopathogenesis of psoriasis, this paper introduces three novel, potential treatments for this clinical conundrum: (i) cannabinoids, which exert inhibitory effects on antigen processing and macrophage/T-cell interaction and also on the release of IL-2, TNF-alpha and nitric oxide from immune cells; (ii) loratadine, which is an antihistamine capable of increasing [corrected] the cAMP/cGMP ratio and the production of leukotriene B4; and (iii) allopurinol, which scavenges free radicals, inhibits the production of TNF-alpha, and downregulates the expression of intercellular adhesion molecule-1 and P2X7 receptors on monocytes/macrophages, which are involved in antigen presentation and production of the inflammatory response, respectively. Importantly, allopurinol, especially in combination with cyclosporin, has been shown to be effective against experimental autoimmune uveitis, which, like psoriasis, is a cell-mediated autoimmune disorder.     

Genetic characterization of the causative agent of besnoitiosis in goats in Iran on the basis of internal transcribed spacer rDNA and its comparison with <Emphasis Type="Italic">Besnoitia</Emphasis> species of other hosts

This study was conducted to identify genetic characteristics of Besnoitia spp. isolated from goat in Iran. Molecular analysis of two portions of nuclear ribosomal DNA (ITS1 and ITS2) was used for the genetic characterization of the Besnoitia species. Comparison of the sequencing data of the Iranian Besnoitia samples obtained in the present study (GenBank accession number HM008988) with those previously reported for other Besnoitia spp. in the GenBank database revealed a particularly close relationship between the present goat Besnoitia samples and the Besnoitia samples from the cattle, caribou, and equids (Besnoitia besnoiti, Besnoitia tarandi, and Besnoitia bennetti). This is the first use of a genetic approach to interrogate the identity of the species of Besnoitia infecting Iranian goats. Also, the results of the present study showed the occurrence of a similar sequence polymorphism for ITS1 and ITS2 in all Iranian isolates, which exhibit 100% identity in these ribosomal sequences, to those of B. besnoiti previously reported from Israel. Although the ITS1 sequence of Iranian goat isolates is identical to European cow isolates, the ITS2 sequences derived from present Besnoitia genotype differed in one nucleotide position compared with other European B. besnoiti. Further studies should be employed based on this molecular data to identify the natural definitive host in order to complete the life cycle of this distinct genotype of parasite.     

A succinct review of the general and immunological pharmacologic effects of proton pump inhibitors

Proton pump inhibitors (PPI) are a group of anti-ulcer agents. PPI have selective anti-cancer effects via apoptosis of tumour, sensitization of cancer cell to chemotherapy and radiotherapy. Also PPI have anti-malarial and anti-leishmanial activity. Rising of endosomal (P)H inhibits the presentation of antigens that enter cell through endocytosis. PPI can affect transmigration of leucocytes from vessels to inflammatory sites and also can mitigate neutrophile adherence to endothelial cell. PPI increase the intralysosomal (P)H and decrease the expression of intracellular adhesion molecules. Therefore PPI can exert immunomodulation in immunological diseases through hampering antigen processing, antigen presentation, and leucocytes transmigration.