Polymorphism of CYP2C19 in patients with cardiovascular incident

CYP2C19 je hemoprotein koji sudjeluje u prvoj fazi biotransformacije ksenobiotika i endogenih molekula te spada u veliku gensku obitelj CYP2C. U ukupnom udjelu metabolizma prve faze biotransformacije zajedno sa CYP2C9 čine 15 %. Lokus gena CYP 2C19 nalazi se na kromosomu 10q24 i sastoji se od 9 egzona. Gen koji kodira ovaj enzim je polimorfan što je značajno za kliničku praksu jer enzim CYP2C19 sudjeluje u metabolizmu više važnih lijekova. Genetički polimorfizam CYP2C19 česta je pojava u općoj populaciji sa značajnom međuetničkom varijabilnosti u učestalosti fenotipova. Tako je u bijeloj populaciji incidencija sporih metabolizatora 1-5%, 13-23% u azijata, 6% među Etiopljanima, te 70% među stanovništvom Vanuatu. Dosadašnja istraživanja navode zastupljenost CYP2C19*2 i CYP2C19*3 u 95 % osoba sporih metabolizatora. Najčešći polimorfni alel u bjelačkoj populaciji je alel 2C19*2, a u azijatskoj alel 2C19*3 koji kodiraju inaktivni enzim. Bitniji protektivni čimbenici u očuvanju integriteta endotela krvnih žila i hemostaze su produkti arahidonske kiseline (AK) poput epoksieikosatrienoične kiseline (EET) koja nastaje metabolizmom AK putem enzima CYP. Mutirani aleli CYP2C19*2 i CYP2C19*3 kodiraju enzim sa smanjenom katalitičkom funkcijom što dovodi do smanjenja koncentracije EETs-a i porasta koncentracije proupalnih citokina (IL-6 i hs-CRP) posljedično tome do ubrzanog razvoja i progresije ateroskleroze koja je glavni etiološki čimbenik kardiovaskularnih i neurovaskularnih bolesti (AKS, MU). Jedan od supstrata enzima CYP2C19 je i lijek klopidogrel, koji sprječava agregaciju trombocita i razvoj tromboze stoga se koristi u primarnoj i sekundarnoj prevenciji kardiovaskularnih i kardioembolijskih događaja (npr. CE MU). Povećan rizik za razvoj tih poremećaja dovodi se u svezu s genetičkom rezistencijom na klopidogrel kao posljedica prisutnosti bar jednog varijantnog alela CYP2C19*2/*3.CYP2C19 is a hemoprotein participating in the first phase of biotransformation of xenobiotics and endogenous molecules and represents a large gene family CYP2C. The total share of the first phase of metabolic biotransformation with CYP2C9 make up 15%. CYP2C19 gene locus is located on chromosome 10q24 and consists of 9 exons. The gene encoding this enzyme is polymorphic and it is important for clinical practice because of the CYP2C19 enzyme involved in the metabolism of several important drugs. Genetic polymorphism of CYP2C19 is common in the general population with significant inter-ethnic variability in phenotype distribution. The incidence of slow metabolizers is 1-5%, 13-23%, 6% and 70% in Caucasian, Asian, Ethiopian, and Vanuatu population respectively. Previous researches suggest the presence of CYP2C19*2 and CYP2C19*3 in 95% of slow metabolizers. The most common polymorphic allele in the Caucasian population is allele 2C19*2 and 2C19*3 allele in Asian population encoding the inactive enzyme. Some of the most important protective factors in preserving the integrity of endothelium in blood vessels and hemostasis are products of arachidonic acid (AA), such as epoksieicosatrienoic acid that is metabolised by CYP enzymes. Mutant alleles CYP2C19*2 and CYP2C19*3 encode an enzyme with reduced activity that results in reduced concentration of EETs and increased concentration of proinflamatory cytokines (IL-6 and hs-CRP) consequently leading to rapid development and progression of atherosclerosis, which is a major etiologic factor of cardiovascular and neurovascular diseases (ACS, stroke). One of the substrates of CYP2C19 enzyme is antiplatelet drug clopidogrel, which prevents the development of thrombosis and is used in primary and secondary prevention of cardiovascular and cardioembolic events (eg. CE MU). Increased risk of these disorders is brought into connection with genetic resistance to clopidogrel as a result of the presence of at least one variant allele CYP2C19 *2 / *3

Polymorphism of CYP2C19 in patients with cardiovascular incident

CYP2C19 je hemoprotein koji sudjeluje u prvoj fazi biotransformacije ksenobiotika i endogenih molekula te spada u veliku gensku obitelj CYP2C. U ukupnom udjelu metabolizma prve faze biotransformacije zajedno sa CYP2C9 čine 15 %. Lokus gena CYP 2C19 nalazi se na kromosomu 10q24 i sastoji se od 9 egzona. Gen koji kodira ovaj enzim je polimorfan što je značajno za kliničku praksu jer enzim CYP2C19 sudjeluje u metabolizmu više važnih lijekova. Genetički polimorfizam CYP2C19 česta je pojava u općoj populaciji sa značajnom međuetničkom varijabilnosti u učestalosti fenotipova. Tako je u bijeloj populaciji incidencija sporih metabolizatora 1-5%, 13-23% u azijata, 6% među Etiopljanima, te 70% među stanovništvom Vanuatu. Dosadašnja istraživanja navode zastupljenost CYP2C19*2 i CYP2C19*3 u 95 % osoba sporih metabolizatora. Najčešći polimorfni alel u bjelačkoj populaciji je alel 2C19*2, a u azijatskoj alel 2C19*3 koji kodiraju inaktivni enzim. Bitniji protektivni čimbenici u očuvanju integriteta endotela krvnih žila i hemostaze su produkti arahidonske kiseline (AK) poput epoksieikosatrienoične kiseline (EET) koja nastaje metabolizmom AK putem enzima CYP. Mutirani aleli CYP2C19*2 i CYP2C19*3 kodiraju enzim sa smanjenom katalitičkom funkcijom što dovodi do smanjenja koncentracije EETs-a i porasta koncentracije proupalnih citokina (IL-6 i hs-CRP) posljedično tome do ubrzanog razvoja i progresije ateroskleroze koja je glavni etiološki čimbenik kardiovaskularnih i neurovaskularnih bolesti (AKS, MU). Jedan od supstrata enzima CYP2C19 je i lijek klopidogrel, koji sprječava agregaciju trombocita i razvoj tromboze stoga se koristi u primarnoj i sekundarnoj prevenciji kardiovaskularnih i kardioembolijskih događaja (npr. CE MU). Povećan rizik za razvoj tih poremećaja dovodi se u svezu s genetičkom rezistencijom na klopidogrel kao posljedica prisutnosti bar jednog varijantnog alela CYP2C19*2/*3.CYP2C19 is a hemoprotein participating in the first phase of biotransformation of xenobiotics and endogenous molecules and represents a large gene family CYP2C. The total share of the first phase of metabolic biotransformation with CYP2C9 make up 15%. CYP2C19 gene locus is located on chromosome 10q24 and consists of 9 exons. The gene encoding this enzyme is polymorphic and it is important for clinical practice because of the CYP2C19 enzyme involved in the metabolism of several important drugs. Genetic polymorphism of CYP2C19 is common in the general population with significant inter-ethnic variability in phenotype distribution. The incidence of slow metabolizers is 1-5%, 13-23%, 6% and 70% in Caucasian, Asian, Ethiopian, and Vanuatu population respectively. Previous researches suggest the presence of CYP2C19*2 and CYP2C19*3 in 95% of slow metabolizers. The most common polymorphic allele in the Caucasian population is allele 2C19*2 and 2C19*3 allele in Asian population encoding the inactive enzyme. Some of the most important protective factors in preserving the integrity of endothelium in blood vessels and hemostasis are products of arachidonic acid (AA), such as epoksieicosatrienoic acid that is metabolised by CYP enzymes. Mutant alleles CYP2C19*2 and CYP2C19*3 encode an enzyme with reduced activity that results in reduced concentration of EETs and increased concentration of proinflamatory cytokines (IL-6 and hs-CRP) consequently leading to rapid development and progression of atherosclerosis, which is a major etiologic factor of cardiovascular and neurovascular diseases (ACS, stroke). One of the substrates of CYP2C19 enzyme is antiplatelet drug clopidogrel, which prevents the development of thrombosis and is used in primary and secondary prevention of cardiovascular and cardioembolic events (eg. CE MU). Increased risk of these disorders is brought into connection with genetic resistance to clopidogrel as a result of the presence of at least one variant allele CYP2C19 *2 / *3

Electroorganic Chemistry. VII. The Role of Mercuric Salts in the Electroreduction of Benzylic Bromides

Electroduction of a variety of benzylic mono- and 1,3-dibromides and of benzylmer curie halides at stirred mercury pool cathode leads to products that support a mechanism for the electro- duction of bromides that involves organomercury(I) intermediates and perhaps mercury (I) dimers. Products f ormed in the presence or absence of strongly adsorbed but eleotrochemically indifferent species suggest that monomolecular versus bimolecular reactions of the adsorbed organomercury(I) intermediates or dimers are strongly influenced by the presence of such species and that in some cases the reaction can be directed to one or another final product, providing a measure of control in synthetic applications

Nova minimalno invazivna transoralna endoskopski asistirana metoda za liječenje prijeloma kondila mandibule u Hrvatskoj: prikaz slučaja i pregled literature

Mandibular fractures, particularly condylar process fractures, are common in maxillofacial surgery and require effective treatment methods that minimize complications while ensuring functional and esthetic recovery. Objectives: This paper presents two cases of mandibular condylar process fractures treated using a transoral endoscopically assisted technique (EATA), thus marking the first documented application of this approach in Croatia. The aim was to evaluate the efficacy of this minimally invasive method compared to traditional extraoral approaches, which often carry risks such as visible scarring, facial nerve injury, and prolonged postoperative recovery. Methods: A 30° rigid endoscope and specialized angled instruments were utilized in both cases to achieve precise visualization, reduction, and fixation of the fractures. The first case involved a young male with a double mandibular fracture, while the second case addressed an isolated condylar fracture in an older female with comorbidities. Results: Both patients were successfully treated without complications, including facial nerve injury, hematomas, or salivary fistulas. Hospitalization periods were shorter compared to traditional approaches, and recovery included restored temporomandibular joint function (TMJ), stable occlusion, and the absence of visible scars. The EATA method proved to be safe and effective, offering numerous advantages such as reduced morbidity, minimal soft tissue trauma, and superior aesthetic outcomes. Despite requiring specialized equipment and additional surgical training, EATA has significant potential to become a standard treatment modality for mandibular fractures. Conclusion: The findings of this study contribute to the growing body of evidence supporting the clinical benefits of this minimally invasive technique.Frakture mandibule, osobito one kondilarnog nastavka, česte su u maksilofacijalnoj kirurgiji i zahtijevaju učinkovite metode liječenja koje minimiziraju komplikacije, a istodobno osiguravaju funkcionalni i estetski oporavak. U ovom radu predstavljena su dva slučaja prijeloma kondilarnog nastavka mandibule liječenih transoralnom endoskopski asistiranom tehnikom (EATA), što je prvo dokumentirano primijenjeno korištenje toga pristupa u Hrvatskoj. Cilj: Cilj je bio procijeniti učinkovitost te minimalno invazivne metode u usporedbi s tradicionalnim ekstraoralnim pristupima koji su često rizični zbog vidljivih ožiljaka, ozljeda facijalnoga živca i produljenoga postoperativnog oporavka. Metode: U oba slučaja korišten je 30° kruti endoskopski specijalni kutni instrument za postizanje precizne vizualizacije, redukcije i fiksacije fraktura. Prvi slučaj uključivao je mladog muškarca s dvostrukom frakturom mandibule, a u drugom slučaju riječ je o izoliranoj frakturi kondilarnog procesa kod starije žene s komorbiditetima. Oba pacijenta uspješno su liječena bez komplikacija, uključujući ozljedu facijalnog živca, hematome ili salivarne fistule. Rezultati: Vrijeme hospitalizacije bilo je kraće u usporedbi s tradicionalnim pristupima, a oporavak je uključivao obnovljenu funkciju temporomandibularnoga zgloba (TMJ), stabilnu okluziju i odsutnost vidljivih ožiljaka. Metoda EATA pokazala se sigurnom i učinkovitom s mnogobrojnim prednostima poput smanjene morbidnosti, minimalne traume mekih tkiva i superiornih estetskih rezultata. Iako zahtijeva specijalnu opremu i dodatnu kiruršku izobrazbu, EATA ima znatan potencijal da postane standardni modalitet liječenja za frakture mandibule. Zaključak: Nalazi u ovom istraživanju pridonose sve brojnijim dokazima koji podržavaju kliničke prednosti ove minimalno invazivne tehnike

Tumori žlijezda slinovnica

Tumori žlijezda slinovnica čine 3-6 % svih tumora glave i vrata, s najvećom učestalošću u parotidnoj žlijezdi. Etiologija nije u potpunosti razjašnjena, no poznati su određeni rizični čimbenici poput izloženosti zračenju, kemijskim agensima i specifičnim genetskim mutacijama. Dobroćudni tumori, kao što su pleomorfni adenom i Warthinov tumor, obično imaju povoljnu prognozu, dok maligni, poput mukoepidermoidnog i adenoidnog cističnog karcinoma, zahtijevaju agresivniji terapijski pristup. Dijagnostički postupci obuhvaćaju klinički pregled, citološku punkciju pod ultrazvučnom kontrolom te slikovne metode (MR i MSCT), dok je liječenje primarno kirurško. Kod benignih tumora često se izvodi parcijalna parotidektomija uz očuvanje funkcije facijalnog živca, dok maligni tumori zahtijevaju radikalnije zahvate uz adjuvantnu terapiju. Napredak kirurških tehnika smanjio je učestalost komplikacija, no potencijalne postoperativne posljedice uključuju parezu facijalnog živca i Freyin sindrom. Pravovremena dijagnoza i multidisciplinarni pristup ključni su za optimalne ishode

Kirurško liječenje velofaringealne insuficijencije sluznično-mišićnim stražnjim faringealnim režnjem - je li to kontraindikacija za nosnu intubaciju? Pregledni članak

Velopharyngeal insufficiency is a disorder where the soft palate directs the air through the nose. It is often present in patients with previous cleft or short palate, but also in many other conditions. Symptoms are primarily to be found in speech, with very distinct nasal sound. After clinical evaluation and nasal endoscopy, surgery is considered. Several surgical techniques are in use, with posterior pharyngeal flap pharyngoplasty being most widely used. This method leaves the base of the posterior pharyngeal flap attached to the posterior pharyngeal wall, with two lateral ports on each side of the flap. Permanent nasopharyngeal obstruction is a very challenging pathology for anesthesiologists in case of mandatory nasal intubation since it is a relative contraindication for nasal intubation. Patients with previous palatoplasty will regularly appear in our routine anesthetic practice, in all surgical segments. The high risk of damage to the flap with possible bleeding can put the anesthesiologist in a very unpleasant situation if not aware of the permanent effect of this surgery. During preanesthetic assessment, if there is information on a previous pharyngoplasty, one should consider alternative options for nasotracheal intubation. All nasal insertion procedures must be either avoided or carried out with great caution, under fiberoptic visual control.Velofaringealna insuficijencija stanje je kod kojega meko nepce zrak usmjerava kroz nos umjesto na usta. Česta je kod bolesnika koji su imali rascjep nepca ili imaju kratko nepce, ali javlja se i u drugim bolestima. Simptomi su primarno govorne prirode, s vrlo izraženim nazalnim prizvukom. Nakon kliničkog pregleda i endoskopskog pregleda nazofarinksa odlučuje se o daljnjoj kirurškoj intervenciji. Danas je nekoliko kirurških tehnika u opticaju, no najčešće se rabi faringoplastika s odizanjem sluznično-mišićnog režnja sa stražnjega zida farinksa. Nakon ovog zahvata baza režnja ostaje pričvršćena za stražnji zid farinksa, sa samo dva otvora sa svake lateralne strane režnja. Trajna opstrukcija nazofarinksa zahtjevna je patologija za anesteziologe u slučajevima koji zahtijevaju nosnu intubaciju, jer nova poslijeoperacijska anatomija predstavlja relativnu kontraindikaciju. Bolesnici kojima je učinjena palatoplastika povremeno budu dio rutinske anesteziološke prakse u svim segmentima kirurgije. Visok rizik za ozljedu režnja uz popratno krvarenje može anesteziologa staviti u neugodan položaj ako nije upoznat s posljedicom koja bolesniku ostaje doživotno nakon operacije. Kao dio anesteziološke prijeoperacijske procjene, ako znamo da je bolesniku učinjena faringoplastika, svakako treba razmotriti alternativne načine intubacije na nos. Svi postupci koji uključuju umetanje predmeta u nos treba ili izbjegavati ili raditi krajnje oprezno, uz obveznu kontrolu fiberoptičkim bronhoskopom

Electroorganic Chemistry. VI. Mechanism and Product Studies in the Electroreductoin of 1,3-Dibromides

Products of the electroreduction of 1,3-dihromopropane, 1, 3-dibromo-1 -phenylpropane, 1,3-dibromo-1,3 -diphenylpropane, enđo-4-syn-8-dibromodibenzobicyclo[3.2.1] octadiene, and 1,8-bis- (bromomethyl)naphthalene at a mercury cathode were examined. The influence of change in potential, of addition of radical and carbanion scavengers, of added adsorbable species on product distribution, and the presence of organomercurial species in the products implicate a reaction path which involves sequential one electron reductions with the intervention of organomercury(l) radicals and possible dimeric mercury(l) species

THE ACCEPTANCE OF COSMETIC SURGERY SCALE (ACSS) AND ITS CORRELATIONS WITH PSYCHOLOGICAL CHARACTERISTICS AMONG THE CROATIAN POPULATION

Background: This study aimed to examine the results of Acceptance of Cosmetic Surgery Scale among the Croatian population and its correlations with other scales and demographic data. Subject and methods: The sample consisted of 420 people who voluntarily filled out an online questionnaire. They completed demographic questions and four scales: Acceptance of Cosmetic Surgery Scale (ACSS), Rosenberg Self-Esteem Scale (RSES), Satisfaction With Life Scale (SWLS), and Body Appreciation Scale-2 (BAS-2). Results: ACSS scale showed five statistically significant differences between genders and a higher overall score in women, but no significant differences were recorded in three ACSS subscales and the overall ACSS score. In contrast to men, women respondents recorded a significant negative correlation between ACSS subscales score (Social, Consider) and BAS-2 and Satisfaction with life score, while a positive correlation was recorded with BMI. Conclusion: The ACSS score among the Croatian population was higher than the results among the Italian and Serbian population, and similar to the original American study, which tells us that the Croatian population accepts and considers cosmetic surgery a lot. Furthermore, our results are important for practitioners and patients because they revealed correlations between ACSS scores and the self-thinking scale

THE ACCEPTANCE OF COSMETIC SURGERY SCALE (ACSS) AND ITS CORRELATIONS WITH PSYCHOLOGICAL CHARACTERISTICS AMONG THE CROATIAN POPULATION

Background: This study aimed to examine the results of Acceptance of Cosmetic Surgery Scale among the Croatian population and its correlations with other scales and demographic data. Subject and methods: The sample consisted of 420 people who voluntarily filled out an online questionnaire. They completed demographic questions and four scales: Acceptance of Cosmetic Surgery Scale (ACSS), Rosenberg Self-Esteem Scale (RSES), Satisfaction With Life Scale (SWLS), and Body Appreciation Scale-2 (BAS-2). Results: ACSS scale showed five statistically significant differences between genders and a higher overall score in women, but no significant differences were recorded in three ACSS subscales and the overall ACSS score. In contrast to men, women respondents recorded a significant negative correlation between ACSS subscales score (Social, Consider) and BAS-2 and Satisfaction with life score, while a positive correlation was recorded with BMI. Conclusion: The ACSS score among the Croatian population was higher than the results among the Italian and Serbian population, and similar to the original American study, which tells us that the Croatian population accepts and considers cosmetic surgery a lot. Furthermore, our results are important for practitioners and patients because they revealed correlations between ACSS scores and the self-thinking scale

Gingival Hypertrophy in a Child with Hyaline Fibromatosis Syndrome

Hijalini fibromatozni sindrom (HFS) rijedak je autosomno recesivni genetski poremećaj koji karakterizira nakupljanje hijaline tvari u tkivima s kožnim, sluzničkim, koštanim, zglobnim i sistemskim manifestacijama. Bolest je uzrokovana mutacijom gena ANTXR2 koja rezultira sintezom neispravnog transmembranskog proteina, pa se hijalini depoziti prekomjerno talože u međustaničnom prostoru. Prvi znakovi mogu biti prisutni pri rođenju ili tijekom dojenačke dobi, a prvi simptom najčešće je ukočenost zgloba. Ostale manifestacije uključuju zglobne kontrakture, hiperpigmentirane makule kože iznad koštanih prominecija zglobova i hipertrofiju gingive, što je uz potkožne nodule (kvržice), vrlo često simptom koji potiče sumnju na HFS. Napredovanje bolesti uključuje enteropatiju s velikim gubitkom proteina, kroničnu dijareju i česte infekcije. U radu predstavljamo petogodišnju djevojčicu s teškim oblikom gingivne hipertrofije koja je uzrokovala poteškoće s hranjenjem i govorom. Prema našim spoznajama to je prvi pacijent opisan u Hrvatskoj s dokazanom mutacijom gena ANTXR2.Hyaline fibromatosis syndrome (HFS) is a rare autosomal recessive genetic disorder characterized by accumulation of hyalinized fibrous tissue with cutaneous, mucosal, osteoarticular, and systemic involvement. The condition is caused by a mutation of ANTXR2 gene that results in a faulty synthesis of a transmembrane protein which leads up to excessive deposition of hyaline material in extracellular space. The first signs may be present at birth or appear during infancy, and joint stiffness is the first, most common, symptom. Other manifestations include joint contractures, hyperpigmented macules over bony prominences of the joints, and gingival hypertrophy. The symptom that raises suspicion of HFS is present later, along with subcutaneous growths. The progression of the disease includes enteropathy with extensive protein loss, chronic diarrhea and frequent infections. We present a case of a five-year-old girl with severe gingival hypertrophy that caused difficulties in eating and speaking. To the best of our knowledge, this is also the first patient in Croatia with a confirmed ANTXR2 gene mutation described in the literature