Helminth parasites that inhabit mammalian body surfaces have a highly evolved relationship with the immune system. Many of these resident helminths carry out functions to ensure their survival in the hosts. To attain this objective helminth parasites adopt immunoregulatory mechanisms to counter host’s hostile immune response. Indeed, immunomodulatory molecules have been discovered in the worm’s extracts and in their excretion/secretion. In this review, we discuss the state of our understanding of the interplay between helminths and immune pathways. We also highlight the key challenges that must be confronted in identification of the helminth-derived molecules involved in immune modulation.  We consider whether helminth-derived signaling hold promise for the design of novel therapeutic approaches for the treatment of inflammatory disorders (inflammatory bowel disease, allergies, and autoimmune diseases).

Genetic polymorphisms in diabetes: Influence on therapy with oral antidiabetics Due to new genetic insights, etiologic classification of diabetes is under constant scrutiny. Hundreds, or even thousands, of genes are linked with type 2 diabetes. Three common variants (Lys23 of KCNJ11, Pro12 of PPARG, and the T allele at rs7903146 of TCF7L2) have been shown to be predisposed to type 2 diabetes mellitus across many large studies. Individually, each of these polymorphisms is only moderately predisposed to type 2 diabetes. On the other hand, monogenic forms of diabetes such as MODY and neonatal diabetes are characterized by unique clinical features and the possibility of applying a tailored treatment. Genetic polymorphisms in drug-metabolizing enzymes, transporters, receptors, and other drug targets have been linked to interindividual differences in the efficacy and toxicity of a number of medications. Mutations in genes important in drug absorption, distribution, metabolism and excretion (ADME) play a critical role in pharmacogenetics of diabetes. There are currently five major classes of oral pharmacological agents available to treat type 2 diabetes: sulfonylureas, meglitinides, metformin (a biguanide), thiazolidinediones, and α-glucosidase inhibitors. Other classes are also mentioned in literature. In this work, different types of genetic mutations (mutations of the gene for glucokinase, HNF 1α, HNF1β and Kir6.2 and SUR1 subunit of KATP channel, PPAR-γ, OCT1 and OCT2, cytochromes, direct drug-receptor (KCNJ11), as well as the factors that influence the development of the disease (TCF7L2) and variants of genes that lead to hepatosteatosis caused by thiazolidinediones) and their influence on the response to therapy with oral antidiabetics will be reviewed. Genetički polimorfizmi u dijabetesu: Utjecaj na terapiju oralnim antidijabeticima Dijabetes tipa 2 dosegao je proporcije epidemije u SAD (> 18 milijuna) i cijelom svijetu (170 milijuna oboljelih osoba) te ima tendenciju daljnjeg dramatičnog rasta. Stoga se u posljednje vrijeme ulažu napori da se otkriju i razviju novi farmakološki agensi za liječenje ove bolesti. Klasifikacija šećerne bolesti proširena je uspjesima istraživača na području genetike. Da bismo razumjeli farmakogenetiku antidijabetika neophodno je razumjeti genetiku samog dijabetesa. Kao što će biti prikazano u ovom radu veliki broj gena koji su povezani s razvojem dijabetesa takođe utječe i na odgovor na terapiju antidijabeticima. S druge strane, mutacije gena koji utječu na ADME (apsorpcija, distribucija, metabolizam i ekskrecija) lijeka imaju značajan utjecaj na farmakogenetiku oralnih antidijabetika. Utvrđeno je da je dijabetes genetički heterogena bolest. Uobičajeni oblici dijabetesa su gotovo uvijek poligenski i za razvoj same bolesti vrlo su značajne snažne interakcije među različitim genima kao i između gena i okoliša. Zbog toga mutacije ili polimorfizmi koji u manjoj mjeri utječu na funkciju gena mogu postati klinički značajni samo u slučaju kada se kombiniraju s drugim faktorima odnosno genima. Smatra se da u razvoju dijabetesa mogu sudjelovati stotine pa čak i tisuće gena. Do 2006. identificirano je nekoliko uobičajenih alela koji povećavaju rizik za razvoj dijabetesa, od kojih su najznačajniji PPARG (Pro12), KCNJ11 (Lys23) i TCF7L2 (T na rs7903146). Do danas je najveći uspjeh postignut u identifikaciji gena odgovornih za razmjerno rijetke oblike ove bolesti poput »Maturity-onset diabetes of the young« (MODY) i neonatalnog dijabetesa. Monogenske oblike dijabetesa odlikuju jedinstvene kliničke karakteristike i mogućnost primjene individualnog tretmana. Genetički polimorfizmi enzima koji utječu na metabolizam lijekova, transportera, receptora i drugih ciljeva djelovanja lijekova povezani su s interindividualnim razlikama u efikasnosti i toksičnosti mnogih lijekova. Vrlo je važno da se na temelju farmakogenetičkih istraživanja mogu predvidjeti neki neželjeni efekti lijekova. Trenutačno postoji pet glavnih klasa oralnih antidijabetika: sulfoniluree, meglitinidi, metformin (bigvanid), tiazolidindioni i inhibitori α-glukozidaze. U literaturi se također spominju inhibitori dipeptidil peptidaze IV (DPP-IV), selektivni antagonisti kanabinoidnog receptora 1 (CB-1), mimetici glukagonu sličnog peptida 1 i mimetici amilina. Razumijevanje mehanizama koji rezultiraju disfunkcijom β stanica na fiziološkom i molekularnom nivou neophodno je za napredak u razumijevanju tretmana dijabetesa. U ovom radu dat je pregled različitih genetičkih mutacija (mutacije gena za glukokinazu, HNF 1α, HNF1β, Kir6.2 i SUR 1 podjedinicu KATP kanala β stanica, PPAR-γ, OCT1 i OCT2, citohrome, KCNJ11, faktore koji utječu na razvoj bolesti (TCF7L2) i varijante gena koji dovode do hepatosteatoze uzrokovane tiazolidindionima) te njihov utjecaj na odgovor na terapiju oralnim antidijabeticima.

Lilium martagon L. var. cattaniae Vis. (Liliaceae) is endemic plant of Dinaridi mountain. In this work we established protocol for fast in vitro propagation and multiplication of Lilium martagon var. cattaniae. The aim was to enable fast production of plant material as potential source of pharmaceutically valuable secondary metabolites. Seeds of L.martagon var. cattaniae were germinated on a Murashige and Skoog basal medium with a supplement of 0.15 mg/l gibberellic acid (GA3), and multiplication was performed on MS medium supplemented with 0.1 mg/l gibberellic acid (GA3), 0.2 mg/l indole-3-butyric acid (IBA) and 0.5 mg/l 6-ben- zylaminopurine (BAP). We used ultrasound assisted extraction to prepare extracts of leaves and bulbs of Lilium martagon var. cattaniae, which were evaluated for their genotoxic potential using Allium test and cytokinesis-block micronucleus test in human lymphocytes culture. There was statistically significant difference between all used concentrations of lilium extracts and control on proliferation of cells of root tip of onion (Allium cepa). In cytokinesis-block micronucleus test no statistically significant difference between frequencies of analyzed parameters in samples treated with tested concentrations of extracts and control was obtained.