From Genomics to Metabolomics of Analgesics in Children

Personalizirana medicina, odnosno individualizirana terapija lijekovima prema bolesnikovoj genetici očekivano se trebala razviti iz projekta humanoga genoma. Farmakogenomika proučava interakciju između ljudskoga genoma i kliničkog odgovora na lijek. Međutim, složenost interakcija između lijeka i pacijenta ne ovisi samo o bolesnikovu genomu već i o mnogima drugim čimbenicima, kao okolišnim faktorima, interakcijama lijek – lijek, polimorfizmu u transporterima i receptorima. U djece je situacija još složenija jer u obzir treba uzeti ontogenomiku, gdje je razvoj ključnih tjelesnih enzima vezan uz kronološku dob djeteta, koja stvara varijabilnost i u farmakokinetici i u farmakodinamici.Personalised medicine or individualised medicamentous treatment based on patient’s genetics was expected to develop from the human genome project. Pharmacogenomics is a science investigating interactions between human genome and clinical drug response. However, the complexity of drug-patient interactions is not only patient genome dependent, but it also depends on many other factors like environmental, drug to drug interactions, and transporter and receptor polymorphism. The situation in children is even more complex given ontogenomics and the development of functional enzymes related to the chronological age of the child, which in turn creates variability in pharmacokinetics and pharmacodynamics

Serious complications of an obstructive upper airway infection in a young child

A 15-month old boy was admitted to our intensive care unit (ICU) cyanotic, unresponsive, apneic, pulseless, with fixed, dilated pupils and a Glasgow Coma Score (GCS) of 3/15. Prompt cardiopulmonary resuscitation (CPR) was initiated and cardiac function was resumed after 10 minutes. The boy was intubated but could not be ventilated because of a thick, viscous secretion obstructing the trachea and causing total airway obstruction. Bronchoscopy revealed laryngotracheitis as the reason for airway obstruction. A computed tomography (CT) scan of the brain showed diffuse edema and ischemic brain injury, which were considered responsible for the boy\u27s comatose situation. Clinical status remained unchanged for 11 days, after which the boy was transported to another hospital. In children presenting with upper airway obstructing syndromes, not responding to therapy, the diagnosis of bacterial tracheitis should be considered and the child should be monitored in a pediatric intensive care unit

Changes in the composition and phenolic compounds content in the leaves of black grapevine varieties during different growing stages

Fenolni spojevi predstavljaju sekundarne biljne metabolite koji imaju vrlo važnu fiziološku i morfološku ulogu u rastu i reprodukciji biljke pružajući joj i zaštitu protiv patogena i predatora. Cilj ovoga istraživanja je dobiti pregled promjena u sastavu i sadržaju fenolnih spojeva odnosno flavonola, flavanola, hidroksicimetnih i hidroksibenzojevih kiselina prisutnih u listovima četiri različite crne sorte vinove loze. Ekstrakti su analizirani tekućinskom kromatografijom visoke djelotvornosti. Dobivenim rezultatima utvrđena je značajna varijabilnost u masenim udjelima fenolnih spojeva između sorata po pojedinim terminima uzorkovanja, kao i značajna varijabilnost u sadržaju fenolnih spojeva unutar iste sorte tijekom različitih termina uzorkovanja.Phenolic compounds represent secondary plant metabolites which play an important physiological and morphological role in plant growth and reproduction. They also provide a protection against pathogens and predators. The aim of this study is to obtain an overview of changes in the composition and phenolic compounds content, more precisely flavonols, flavanols, hydroxycimetic and hydroxybenzoic acids present in the leaves of four different grapevine varieties. The extracts were analyzed by high performance liquid chromatography. Based on the obtained results, significant variability in mass shares of phenolic compounds between varieties was determined by individual sampling terms, as well as significant variability in the content of phenolic compounds within the same variety during different sampling terms

THE PHARMACOKINETIC AND PHARMACODYNAMIC CHARACTERISTICS OF ANALGESICS IN CHILDREN

Za veliki broj lijekova, pa tako i za analgetike, iz etičkih se razloga ne provode farmakološke studije u djece tijekom preregistracijskog ispitivanja lijeka. Dizajniranje ovakvih studija vrlo je zahtjevno i teško provedivo. Pojam „djeca“ uključuje vrlo heterogenu skupinu, od prematurne novorođenčadi do puberteta i adolescencije. To je razdoblje života u kojem se odvija kompletan razvoj i sazrijevanje metaboličkih mehanizama odgovornih za procese farmakodinamike i farmakokinetike. Procjena intenziteta boli u djece opterećena je brojnim teškoćama. Mnogi analgetici imaju relativno malu terapijsku širinu i kliničari su suočeni s realnom opasnošću od predoziranja. Preporuke za doziranje pojedinog analgetika u djece često ne postoje ili su bazirane na relativno malim kliničkim studijama. Multicentrična suradnja je u novije vrijeme omogućila pojavu kvalitetnih farmakodinamskih i farmakokinetskih ispitivanja za osnovne analgetike kao što su paracetamol, tramadol i morfin.For a large number of medicines, analgesics included, ethical obligations do not permit pharmacological studies in children during pre-registration medicine testing. The very design of such studies is demanding and they are difficult to conduct. The term “children” includes a number of highly diverse groups, from premature neonates to children in puberty and adolescence. Childhood is a period of life in which the complete development and maturation of metabolic paths occurs, including maturation of the metabolic mechanisms responsible for pharmacokinetic and pharmacodynamic processes. The assessment of pain intensity in children presents a number of difficulties, too. Numerous analgesics have a relatively narrow therapeutic width and therefore clinicians are faced with the objective danger of overdosing. Dosage recommendations for specific analgesic agents in children either do not exist or they are based on relatively small clinical studies. Recent multicentric cooperation has made it possible top conduct high quality pharmacodynamic and pharmacokinetic testing for basic analgesics such as acetaminophen, morphine and tramadol

THE PHARMACOKINETIC AND PHARMACODYNAMIC CHARACTERISTICS OF ANALGESICS IN CHILDREN

Za veliki broj lijekova, pa tako i za analgetike, iz etičkih se razloga ne provode farmakološke studije u djece tijekom preregistracijskog ispitivanja lijeka. Dizajniranje ovakvih studija vrlo je zahtjevno i teško provedivo. Pojam „djeca“ uključuje vrlo heterogenu skupinu, od prematurne novorođenčadi do puberteta i adolescencije. To je razdoblje života u kojem se odvija kompletan razvoj i sazrijevanje metaboličkih mehanizama odgovornih za procese farmakodinamike i farmakokinetike. Procjena intenziteta boli u djece opterećena je brojnim teškoćama. Mnogi analgetici imaju relativno malu terapijsku širinu i kliničari su suočeni s realnom opasnošću od predoziranja. Preporuke za doziranje pojedinog analgetika u djece često ne postoje ili su bazirane na relativno malim kliničkim studijama. Multicentrična suradnja je u novije vrijeme omogućila pojavu kvalitetnih farmakodinamskih i farmakokinetskih ispitivanja za osnovne analgetike kao što su paracetamol, tramadol i morfin.For a large number of medicines, analgesics included, ethical obligations do not permit pharmacological studies in children during pre-registration medicine testing. The very design of such studies is demanding and they are difficult to conduct. The term “children” includes a number of highly diverse groups, from premature neonates to children in puberty and adolescence. Childhood is a period of life in which the complete development and maturation of metabolic paths occurs, including maturation of the metabolic mechanisms responsible for pharmacokinetic and pharmacodynamic processes. The assessment of pain intensity in children presents a number of difficulties, too. Numerous analgesics have a relatively narrow therapeutic width and therefore clinicians are faced with the objective danger of overdosing. Dosage recommendations for specific analgesic agents in children either do not exist or they are based on relatively small clinical studies. Recent multicentric cooperation has made it possible top conduct high quality pharmacodynamic and pharmacokinetic testing for basic analgesics such as acetaminophen, morphine and tramadol

Poništenje trombocitopenije i krvarenja kod nedonoščeta primjenom rekombinantnog aktiviranog faktora VII : prikaz slučaja

A male neonate, born at 26 weeks of postmenstrual age, with intracranial hemorrhage grade IV and thoracic drainage for artificial tension pneumothorax on day 6 of his life is presented. Despite prior transfusions, the preprocedural hemogram showed marked anemia and thrombocytopenia. To reverse thrombocytopenia and to avoid volume overload, the patient was administered 110 μg kg-1 of recombinant activated factor VII (rFVII a) and drainage of the pneumothorax was performed uneventfully.Opisuje se muško nedonošće rođeno s 26 tjedana postmenstrualne dobi, s intrakranijskim krvarenjem IV . stupnja, u kojega se 6. dana života morala učiniti torakalna drenaža zbog tenzijskog pneumotoraksa. Iako je dijete već dobivalo transfuzije, u hemogramu je neposredno prije torakalne drenaže bila prisutna značajna anemija i trombocitopenija. S ciljem povećanja broja trombocita bez dodatnog opterećivanja intravaskularnog volumena novorođenče je dobilo 110 μg kg-1 rekombinantnog aktiviranog faktora VII (rFVII a) i potom je pneumotoraks dreniran