Albumini u bolesnika sa solidnim tumorima

The manufacture of albumin derived from human plasma started by Professor E. J. Cohn during World War II has expanded into international business over the past sixty years (1). In vital situations, albumin was used as a plasma expander. This is a biological preparation and always potentially dangerous. The manufacture of albumin is getting more and more expensive as the preparation has to meet standards ever higher. With the market abundant in artificial macro-molecular plasma expanders, improved parenteral nutrition, and studies questioning the effectiveness of albumin use, the administration of albumin has been reduced. Because of the nature of their disease and chemoradiotherapy treatment, patients with tumors are prone to having low protein levels. However, indications for albumin therapy are restricted, the same as that in other patient groups. With the quality parenteral and enteral nutrition available, the use of albumin to correct hypoalbuminemia is not justified.Proizvodnju albumina iz ljudske plazme započeo je profesor Cohn E. J. tijekom Drugog svjetskog rata; koja je u posljednjih šezdesetak godina prerasla je u internacionalni biznis (1). U vitalnim situacijama; albumin je upotrebljavan kao plazmaekspander. To je biološki preparat i uvijek je potencijalno opasan. Proizvodnja albumina sve je skuplja; jer preparat mora zadovoljavati sve više i više standarde. Uz bogato tržište umjetnih makromolekularnih plazmaekspandera; unaprijeđene intravenske prehrane i studije koje govore o upitnom djelovanju albumina; njegova primjena je u padu. Tumorski bolesnici; zbog prirode bolesti i liječenja kemoradioterapijom; skloni su nižim razinama proteina. Međutim; indikacije albuminske terapije su restriktivne; iste kao i kod ostalih skupina bolesnika. Uporaba albumina za korekciju hipoalbuminemije nije opravdana pored kvalitetne parenteralne i enteralne prehrane

Albumini u bolesnika sa solidnim tumorima

The manufacture of albumin derived from human plasma started by Professor E. J. Cohn during World War II has expanded into international business over the past sixty years (1). In vital situations, albumin was used as a plasma expander. This is a biological preparation and always potentially dangerous. The manufacture of albumin is getting more and more expensive as the preparation has to meet standards ever higher. With the market abundant in artificial macro-molecular plasma expanders, improved parenteral nutrition, and studies questioning the effectiveness of albumin use, the administration of albumin has been reduced. Because of the nature of their disease and chemoradiotherapy treatment, patients with tumors are prone to having low protein levels. However, indications for albumin therapy are restricted, the same as that in other patient groups. With the quality parenteral and enteral nutrition available, the use of albumin to correct hypoalbuminemia is not justified.Proizvodnju albumina iz ljudske plazme započeo je profesor Cohn E. J. tijekom Drugog svjetskog rata; koja je u posljednjih šezdesetak godina prerasla je u internacionalni biznis (1). U vitalnim situacijama; albumin je upotrebljavan kao plazmaekspander. To je biološki preparat i uvijek je potencijalno opasan. Proizvodnja albumina sve je skuplja; jer preparat mora zadovoljavati sve više i više standarde. Uz bogato tržište umjetnih makromolekularnih plazmaekspandera; unaprijeđene intravenske prehrane i studije koje govore o upitnom djelovanju albumina; njegova primjena je u padu. Tumorski bolesnici; zbog prirode bolesti i liječenja kemoradioterapijom; skloni su nižim razinama proteina. Međutim; indikacije albuminske terapije su restriktivne; iste kao i kod ostalih skupina bolesnika. Uporaba albumina za korekciju hipoalbuminemije nije opravdana pored kvalitetne parenteralne i enteralne prehrane

Karcinomska bol i terapija

Cancer pain is not a homogenous and clearly understood pathological process. The best treatment is a combination of drug and non-drug measures. Pain is divided into visceral, bone or neuropathic pain and has characteristics of continuous or intermittent pain. Cancer bone pain therapy remains centered on strong opioid, radiotherapy and bisphosphonates. Invasive procedures are aimed to improve neurological function, ambulation and pain relief. Solid tumors often demand surgery. Treatment of acute postoperative pain is crucial for the prevention of chronic pain. Chemotherapy and radiation sometimes also cause pain. The management of cancer pain has improved because of rapid diagnosis and treatment, understanding of analgesics and the cooperation of patients and their family. The presence of special pain centers in hospitals also raise standard of cancer pain management. Drug therapy with non-opioid, opioid and adjuvant drugs is the base of such management. The side effects must be monitored and timely treated. Methods of regional nerve blockade in pain control are numerous. Placement of epidural, intrathecal and subcutaneous catheters, conductive nerve blocks with continuous delivery of mixed local anesthetics are very successful for selected patients. Conventional physical therapy involving lymphatic drainage is useful. Acupuncture, psychotherapy and similar methods are also applicable.Karcinomska bol nije homogen i potpuno razjašnjen patološki proces. Najbolja terapija je kombinacija medikamentozne terapije i nemedikametoznih postupaka. Možemo je podijeliti na visceralnu, koštanu i neuropatsku bol i ima karakteristike kontinuirane ili povremene boli. Terapija koštane boli fokusirana je na jake opioide, radioterapiju i bifosfonate. Cilj invazivnih metoda liječenja boli je poboljšati neurološku funkciju, pokretljivost i olakšanje boli. Solidni tumori često zahtjevaju operaciju. Liječenje akutne poslijeoperacijske boli je od iznimne važnosti u prevenciji nastanka kronične boli. Kemoterapija i radioterapija ponekad također uzrokuju bol. Liječenje karcinomske boli je poboljšano bržom dijagnostikom i terapijom, boljim poznavanjem analgetika i suradnjom s pacijentom i njegovom obitelji. Postojanje specijaliziranih centara za bol u bolnicama također je podiglo standard u liječenju boli. Liječenje boli medikamentozno neopioidima, opioidima i drugim pomoćnim lijekovima je osnova liječenja boli. Nuspojave lijekova moraju se neprestano pratiti i na vrijeme liječiti. Metode regionalne nervne blokade u liječenju boli su brojne. Plasiranje epiduralnih, intratekalnih i supkutanih katetera s kontinuiranom isporukom mješavine lokalnih anestetika veoma su uspješne kod određenih bolesnika. Fizikalna terapija s limfnom drenažom je korisna. Akupunktura, psihoterapija i slične metode su također primjenjive

Dexmedetomidine in perioperative period

Deksmedetomidin je anestetik koji se svakodnevno koristi u kliničkoj praksi. Prema načinu djelovanja on je selektivni agonist α2-adrenergičkih receptora (α2-AR). Ciljna mjesta djelovanja su α2-AR locusa ceruleusa moždanog debla (sedacija i vagomimetički učinak) i leđne moždine (analgezija). Lijek se u potpunosti biotransformira u organizmu direktnom glukoronidacijom i jetrenim p450 enzimskim sustavom u inaktivne metabolite koji se izlučuju urinom. Njegovo djelovanje je povezano sa analgetskim učincima (inhibicija otpuštanja antinociceptivnih transmitera poput sustance P i glutamata) i sedacijskim učincima kojima se smanjuje potreba za korištenjem opioda u perioperativnom periodu, smanjenom pojavom delirija i agitacijom u jedinicama intenzivnog liječenja. Obzirom na brz početak i predvidljiv prestanak djelovanja, te postojanje antidota, sve češće se koristi u kliničkim uvjetima te se trenutno koristi kao premedikacija, intraoperativno tijekom indukcije i održavanja anestezije, u regionalnoj anesteziji te za sedaciju u jedinicama intenzivnog liječenja. Nadalje, pogodan je za korištenje tijekom kratkotrajnih ambulantnih zahvata poput kolonoskopije, transezofagealne ehokardiografije i litotripsije. Njegovo jedinstveno svojstvo oponašanja prirodnog stanja sna i mogućnosti lakog razbuđivanja te njegov neuroprotektivni učinak, čine ga pogodnim za korištenje kod neurokirurških bolesnika u jedinicama intenzivnog liječenja. Postoje i neželjeni učinci Deksmedetomidina poput izazivanja bradikardije i hemodinamske nestabilnosti zbog čega se preporuča izbjegavanje davanja bolus doza. Posljednje studije također upozoravaju na štetnost dugotrajnog davanja Deksmedetomidina te na povećanu smrtnost u odnosu na pacijente sedirane Propofolom ili Midazolamom.Dexmedetomidine is an anesthetic generally used in clinical practice during perioperative period. It is a selective α2-adrenergic receptor (α2-AR) agonist. The target sites of action are the α2-AR on locus ceruleus of the brainstem (sedation and vagomimetic effect) and the spinal cord (analgesia). The drug is completely biotransformed in the body by direct glucuronidation and the hepatic p450 enzyme system into an inactive metabolite that is excreted in the urine. Its action is associated with analgesic effects (inhibition of the release of antinociceptive transmitters such as substance P and glutamate) and sedation effects that reduce the need for the use of opioids in the perioperative period, reduced occurrence of delirium and agitation in intensive care units. Apparently due to its rapid onset and predictable cessation of action, and the existence of an antidote, it is increasingly used in clinical settings and is currently used as a premedication, during the induction and maintenance of anesthesia intraoperatively, in regional anesthesia and for sedation in intensive care units. Furthermore, it is suitable for use during short-term outpatient procedures such as colonoscopy, transesophageal echocardiography and lithotripsy. Its unique property of imitating the natural state of sleep and the possibility of easy awakening, as well as its neuroprotective effect, make it suitable for use in neurosurgical patients in intensive care units. There are also adverse effects of Dexmedetomidine such as bradycardia and hemodynamic instability, which is why it is recommended to avoid giving a loading dose. The latest studies also warn of the harmfulness of long-term administration of Dexmedtomidine and of increased mortality compared to patients sedated with Propofol or Midazolam

Trombocitna rezistencija na klopidogrelski antiagregacijski učinaku bolesnika sa solidnim tumorima

The anti-aggregating effect of clopidogrel (75 mg/day) on platelet function was monitored in 33 solid tumor patients. Clopidogrel irreversibly blocks the platelet P2Y12 receptor and inhibits platelet aggregation induced by adenosine diphosphate (ADP). Whole blood aggregation was measured using a Siemens PFA-100 aggregometer including the Innovance PFA P2Y cartridge. The mean age of patients was 62 ± 13 years. Among them, there were 19 (58%) males and 14 (42%) females. The values of platelet aggregation >106 seconds and 106 sekunda pokazala je klopidogrelski antiagregacijski učinak u 22 (67%) bolesnika; a vrijednost <106 sekunda uočena je u 11 (33%) bolesnika koji nisu reagirali. Prosječni klopidogrelski antiagregacijski učinak bio je 219 ± 110 sekunda. Agregacijskih razlika između muškaraca i žena nije bilo (p=0;784). Interindividualna agregacijska varijacija bila je 50%. Nije bilo statistički značajne razlike između dvaju mjerenja 7 uzoraka istih osoba u razmaku od mjesec ili više dana; što pokazuje intraindividualnu stabilnost klopidogrelskog djelovanja na trombocitnu agregaciju (p=1;000)

Neurodegenerative changes caused by inhalation anesthetics

Mozak je ciljni organ djelovanja inhalacijskih anestetika. Osjetljivost mozga na oksidacijski stres povezana je sa njegovom izraženom metaboličkom aktivnošću, proizvodnjom ROSa (engl. reactive oxygen species, ROS), velikim brojem mitohondrija i smanjenom enzimskom antioksidativnom aktivnošću. Inhalacijski anestetici, poput Isoflurana i Sevoflurana, utječu na jačanje osjetljivosti mozga na oštećenja oksidativnim stresom te na povećanje aktivnost beta-sekretaze (BACE), enzima koji formira beta-amiloidne plakove i izaziva beta-amiloidnu ovisnu apoptozu živčanih stanica. Nadalje, beta-amiloidni plakovi, kao patološki produkt amiloidnog prekursorskog proteina (APP), predstavljaju važnu značajku za razvoj neurodegenerativnih promjena povezanih sa nastankom Alzheimerove bolesti. Istraživanje prooksidativnih, upalnih i neurotoksičnih učinaka inhalacijskih anestetika, te praćenje razine oksidativnog stresa u moždanom tkivu i nastalih patohistoloških promjena na mozgu štakora vezanih za neurodegenerativna oštećenja i upalu možemo povezati sa dugotrajnim izlaganjem inhalacijskim anesteticima, narušavanjem oksidacijsko/antioksidacijske homeostaze i stvaranje beta-amiloidnih plakova. Razumijevanjem povezanosti izloženosti inhalacijskim anesteticima i nastanku ireverzibilnih neurodegenerativnih promjena sugeriralo bi se poštednijim korištenjem inhalacijskih anestetika utjecati na ograničavanje neurodegenerativnihpromjena vezanih za nastanak Alzheimerove bolesti.Main target of inhalation anesthetics is the brain. The sensitivity of the brain to oxidative stress is associated with its pronounced metabolic activity, production of ROS (reactive oxygen species), large number of mitochondria and reduced enzymatic antioxidant activity. Inhaled anesthetics, such as Isoflurane and Sevoflurane, increase the sensitivity of the brain to oxidative stress damage and increase the activity of beta-secretase (BACE), an enzyme that forms beta-amyloid plaques and causes beta-amyloid-dependent apoptosis of nerve cells. Furthermore, beta-amyloid plaques, pathological product of amyloid precursor protein (APP), represent an important feature for the development of neurodegenerative changes associated with the development of Alzheimer’s disease. By investigation of prooxidative, inflammatory and neurotoxic effects of inhaled anesthetics and analyzing the parameters of oxidative stress levels in brain tissue and pathohistological changes in rat brain related to neurodegenerative damage and inflammation, connection with long-term exposure to inhaled anesthetics disruption of oxidative/antioxidant homeostasis and formation of beta amyloid plaques can be made. By understanding the relationship between exposure to inhaled anesthetics and the occurrence of irreversible neurodegenerative changes it could be suggested to reduce using inhaled anesthetics to limit the neurodegenerative changes associated with the development of Alzheimer’s disease

Imunohistokemijska diferencijacija trostruko negativnog raka dojke

Based on immunohistochemical staining for the basal markers cytokeratin 5/6 (CK 5/6), cytokeratin 14 (CK 14) and P-cadherin, triple negative tumors (TNT) are divided into two groups: 1) basal-like (BL) positive for one or all three markers; and 2) non basal-like (NBL) negative for all three markers. Even though the different origin of the cells of these two types of tumors implies different biological properties, they had been treated as one entity until recently. This paper analyzes TNT collected from 150 patients and distributed into two groups according to the results of immunohistochemical analysis, i.e. BL 116 (77.3%) and NBL 34 (22.67%). In this study, CK 5/6, CK 14 and P-cadherin were used as markers for identifying BL tumors. The immunohistochemical reaction was positive for CK 5/6 in 37%, for CK 14 in 50.86% and for P-cadherin in 68.34% of cases. The subclassification of triple negative breast cancer using the basal markers CK 5/6, CK 14 and P-cadherin has enabled identification of BL and NBL breast cancers in a proportion that is in line with the only accurate analysis of TNT gene expression. Using the mentioned combination of markers in daily practice is easy to perform and economically affordable.Na osnovi imunohistokemijske analize bazalnih biljega citokeratin 5/6 (CK 5/6), citokeratin 14 (CK 14) i P-kadherin trostruko negativni tumori (TNT) su podijeljeni u dvije skupine: 1. basal-like (BL) (pozitivni na jedan ili sva tri biljega) i 2. non basal-like (NBL) (negativni na sva tri biljega). Iako različito podrijetlo stanica ovih dvaju tipova tumora upućuje i na njihova različita biološka svojstva, sve donedavno tretirani su kao jedan entitet. U našem su radu za identifikaciju basal-like tumora korišteni biljezi CK 5/6, CK 14 i P-kadherin. Imunohistokemijska reakacija na CK 5/6 bila je pozitivna u 37%, na CK 14 u 50,86% i na P-kadherin u 68,34% uzoraka. U ovom su radu TNT prikupljeni od ukupno 150 bolesnica razvrstani temeljem imunohistokemijske analize u dvije skupine: basal-like 116 (77,33%) i non basal-like 34 (22,67%). Subklasifikacija TNT dojke uz pomoć bazalnih biljega CK 5/6, CK 14 i P-kadherina omogućila je identifikaciju basal-like i non basal-like tumora dojke u omjeru koji je u skladu s jedino točnom analizom genske ekspresije TNT. Primjena navedene kombinacije biljega u svakodnevnoj je praksi lako izvediva i ekonomski nezahtjevna

Trombocitna rezistencija na klopidogrelski antiagregacijski učinaku bolesnika sa solidnim tumorima

The anti-aggregating effect of clopidogrel (75 mg/day) on platelet function was monitored in 33 solid tumor patients. Clopidogrel irreversibly blocks the platelet P2Y12 receptor and inhibits platelet aggregation induced by adenosine diphosphate (ADP). Whole blood aggregation was measured using a Siemens PFA-100 aggregometer including the Innovance PFA P2Y cartridge. The mean age of patients was 62 ± 13 years. Among them, there were 19 (58%) males and 14 (42%) females. The values of platelet aggregation >106 seconds and 106 sekunda pokazala je klopidogrelski antiagregacijski učinak u 22 (67%) bolesnika; a vrijednost <106 sekunda uočena je u 11 (33%) bolesnika koji nisu reagirali. Prosječni klopidogrelski antiagregacijski učinak bio je 219 ± 110 sekunda. Agregacijskih razlika između muškaraca i žena nije bilo (p=0;784). Interindividualna agregacijska varijacija bila je 50%. Nije bilo statistički značajne razlike između dvaju mjerenja 7 uzoraka istih osoba u razmaku od mjesec ili više dana; što pokazuje intraindividualnu stabilnost klopidogrelskog djelovanja na trombocitnu agregaciju (p=1;000)

Effects of Volatile Anaesthetics and Iron Dextran on Chronic Inflammation and Antioxidant Defense System in Rats

Iron, as an essential microelement, is involved in cell proliferation, metabolism, and differentiation. It also modulates the fate and function of macrophages in hematopoiesis and macrophage-mediated inflammatory responses. On the other hand, anesthetics can affect the inflammatory process by modulating the response to stress or the functions of immune cells. The aim of this paper is to understand how excessive iron intake alters physiological, functional characteristics of peripheral tissues and whether different anesthetics can alter cell metabolism regarding oxidative stress (OS) and inflammation through regulation of macrophage polarization. Y59 rats were injected intraperitoneally with iron dextran solution at a dose of 50 mg/kg or were exposed to inhaled anesthetics sevoflurane and isoflurane and their combination for 28 days every other day. The results show that the use of anesthetics reduces the rat’s organ weight and increases OS in peripheral tissues, leading to M1 macrophage polarization. Excessive iron intake leads to increased OS, inflammation, and an increased ratio of IL-12/IL-10 cytokines to the M1 macrophage phenotype. Iron, in combination with sevoflurane, has a protective effect in tissues showing the M2 phenotype of macrophages. The combination of iron dextran and isoflurane in rats leads to an increase in the erythropoiesis process made possible through the induction of hypoxia