The role of leptin and adiponectin in the development of the metabolic syndrome

Das Metabolische Syndrom hat über die Jahre immer mehr die Aufmerksamkeit auf sich gezogen, da es zu Invalidität und vorzeitigem Tod bei einer steigenden Anzahl an Betroffenen führt. Neben der Umwelt sind immer wieder die Gene und deren Veränderungen worden, die Krankheit zu verursachen. Leptin und Adiponectin, zwei Adipozytokine, sowie ihre Rezeptoren sind das Hauptaugenmerk dieser Diplomarbeit, da sie und ihre genetischen Polymorphismen mit dem Metabolischen Syndrom in Verbindung gebracht worden sind. Genomweite Assoziationsstudien stellen eine neue Vorgehensweise dar, diese genetischen Veränderungen zu finden. Die Ergebnisse der vorliegenden Literaturrecherche sind sehr inkonsistent ausgefallen und weisen darauf hin, dass nach dem derzeitigen Wissensstand nicht gesagt werden kann in welchem Ausmass die Adipozytokine in der Entstehung vom MetS eine Rolle spielen. Im Moment können keine genetischen Screenings zur Risikobewertung empfohlen werden. Das Einfügen von gesunden Verhaltensweisen in das Alltagsleben und nicht ein genetisches Screening sollten im Mittelpunkt der Prävention vom Metabolischen Syndrom sein.The attention to metabolic syndrome has risen constantly over the years as the disease is leading to disability and premature death in an increasing number of affected people. Next to environmental factors, genes and gene variations have been considered to play a role in causation. Leptin and adiponectin, two adipocytokines, as well as their receptors, have been the focus of this thesis as they (together with their polymorphisms) have been linked to metabolic syndrome features. Genome-wide association studies have been a novel approach to find these genetic variations and until now they have reported numerous outcomes. The literature research at hand revealed various results pointing out that current knowledge is not enough to explain to which extent the adipocytokines play a role in the development of MetS. Genetic screenings for risk assessement cannot be recommended at the moment. The incorporation of better health habits to prevent the metabolic syndrome and/or any of its features should be in the focus instead

Detecting and Reporting Adverse Drug Reactions

Hrvatska već više od četrdeset godina ima tradiciju spontanog prijavljivanja sumnji na nuspojave lijekova. Sustav usmjeren na praćenje sigurnosti lijekova i medicinskih proizvoda te otkrivanje promjena u omjeru koristi i rizika naziva se farmakovigilancijski sustav. Nuspojava je svaka štetna i neželjena reakcija na lijek uključujući štetne i neželjene učinke koji su posljedica medikacijskih pogrešaka te primjene lijeka izvan uvjeta odobrenja za stavljanje lijeka u promet poput pogrešne uporabe i zlouporabe lijeka. Prema mehanizmu nastanka, nuspojave možemo podijeliti u pet tipova: nuspojave kao posljedica farmakološkog učinka lijeka, nepredvidive reakcije, reakcije koje traju relativno dulje vrijeme, odgođene reakcije te reakcije povezane s prestankom uzimanja lijeka. Važno je razlikovati nuspojavu od štetnog događaja. Štetni je događaj vremenski povezan s uzimanjem lijeka, ali ne mora biti uzročno-posljedično povezan. Neki se štetni događaj smatra nuspojavom ako postoji sumnja da je bio uzrokovan uzimanjem lijeka. Zdravstveni radnik koji dolazi u doticaj s pacijentom/korisnikom lijeka obvezan je o sumnjama na nuspojave lijeka, osobito ozbiljne i neočekivane, pisano izvijestiti Hrvatsku agenciju za lijekove i medicinske proizvode, a u slučaju cjepiva i Hrvatski zavod za javno zdravstvo. Kako bi prijava bila valjana, potrebno je navesti četiri osnovna podatka. To su podaci o: prijavitelju događaja, pacijentu kod kojeg se dogodila reakcija, lijeku na koji se sumnja da je uzrokovao prijavljenu reakciju te o samoj reakciji koju prijavljujemo. Svaka je prijava nuspojave važna te može pridonijeti sigurnijoj primjeni lijekova, a zdravstveni djelatnici, posebice liječnici i ljekarnici, najčešće su u prilici uočiti te potom prijaviti nuspojavu.The Croatian tradition of spontaneous reporting of suspected adverse drug reactions (ADRs) is over forty years long. The system that focuses on drug safety (before and after marketing authorisation was granted) and detects changes in their benefit/risk ratio is called pharmacovigilance system. An ADR is every harmful and unintended reaction including adverse and undesirable effects resulting from medication errors and administration of the drug outside of conditions the product was approved for, including drug misuse and abuse. According to their mechanism, ADRs can be divided into 5 types: augmented reactions which result from the pharmacological effect of the drug, bizarre reactions (not expected from the known pharmacological actions of the drug), continuing reactions, delayed reactions and end-of-use reactions associated with the withdrawal of a medicine. It is important to distinguish an ADR from an adverse event. ADRs are those adverse events for which there is a reasonable possibility of a causal relationship with the drug/medicinal product. Healthcare professionals (HCPs), who are in contact with the patient or drug user, are obliged to report any suspected ADR, especially if serious and unexpected. The Croatian Agency for Medicinal Products and Medical Devices, and the Croatian Institute for Public Health if vaccines are involved, need to be informed of the report. Specification of minimum criteria is necessary for a valid case report: identifiable reporter, patient, suspect drug, and suspected reaction. Each case report contributes to patient safety and HCPs, particularly doctors and pharmacists, have an opportunity to identify and report ADRs

A common variant of the MACC1 gene is significantly associated with overall survival in colorectal cancer patients

<p>Abstract</p> <p>Background</p> <p>The newly discovered metastasis-associated in colon cancer-1 (MACC1) gene is a key regulator of the HGF/MET pathway. Deregulation of HGF/MET signaling is reported as a prognostic marker for tumorigenesis, early stage invasion, and metastasis. High expression levels of MACC1 have been associated with colon cancer metastasis and reduced survival. Potential links between the genetic diversity of the MACC1 locus and overall survival are unknown. We therefore investigated the association between MACC1 tagging single nucleotide polymorphisms (SNPs) and overall survival in a large cohort of colorectal cancer patients.</p> <p>Methods</p> <p>The study included 318 subjects with histopathologically proven colorectal cancer at the Academic Teaching Hospital Feldkirch, Austria. Survival data were provided by the federal agency for statistics in Austria. Genomic DNA was isolated from formalin-fixed paraffin-embedded specimens; six tagging SNPs (rs1990172, rs3114446, rs10275612, rs3095007, rs3095009, and rs7780032), capturing most of the common variants of the MACC1 locus, were genotyped by SNaPshot assays.</p> <p>Results</p> <p>Over a mean follow up period of 5.3 (± 1.0) years, 94 deaths were recorded. Carriers of the G-allele of SNP rs1990172 showed a significantly decreased overall survival (additive HR = 1.38 [1.05-1.82]; <it>p </it>= 0.023). Multivariate analysis adjusted for age and UICC tumor stage confirmed this result (HR = 1.49 [1.12-1.98]; <it>p </it>= 0.007). Other investigated genetic variants of the MACC1 gene were not significantly associated with overall survival (<it>p</it>-values > 0.05).</p> <p>Conclusions</p> <p>For the first time, our study investigated the influence of MACC1 tagging polymorphisms on overall survival suggesting SNP rs1990172 as a predictor for reduced overall survival in colorectal cancer patients. Further studies will be required to validate our findings.</p