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Pentadecapeptide BPC 157 Reduces Bleeding and Thrombocytopenia after Amputation in Rats Treated with Heparin, Warfarin, L-NAME and L-Arginine
No full textBACKGROUND: BPC 157 is a stable gastric pentadecapeptide recently implicated with a role in hemostasis. While NO is largely implicated in hemostatic mechanisms, in tail-amputation-models under heparin- and warfarin-administration, both the NO-synthase (NOS)-blocker, L-NAME (prothrombotic) and the NOS-substrate L-arginine (antithrombotic), were little investigated. Objective. To investigate the effect of L-NAME and L-arginine on hemostatic parameters, and to reveal the effects of BPC 157 on the L-NAME- and L-arginine-induced hemostatic actions under different pathological condition: tail amputation without or with anticoagulants, heparin or warfarin.
METHODS: Tail amputation, and/or i.v.-heparin (10 mg/kg), i.g.-warfarin (1.5 mg/kg/day for 3 days) were used in rats. Treatment includes BPC 157, L-NAME, L-arginine, per se and their combination.
RESULTS: After (tail) amputation, with or without i.v.-heparin or i.g.-warfarin, BPC 157 (10 μg/kg, 10 ng/kg, i.p., i.v. (heparin), 10 μg/kg i.g. (warfarin)) always reduced bleeding time and/or haemorrhage and counteracted thrombocytopenia. As for L-NAME and/or L-arginine, we noted: L-arginine (100 mg/kg i.p.)-rats: more bleeding, less/no thrombocytopenia; L-NAME (5 mg/kg i.p.)-rats: less bleeding (amputation only), but present thrombocytopenia; L-NAME+L-arginine-rats also exhibited thrombocytopenia: L-NAME counteracted L-arginine-increased bleeding, L-arginine did not counteract L-NAME-thrombocytopenia. All animals receiving BPC 157 in addition (BPC 157 μg+L-NAME; BPC 157 μg+L-arginine, BPC 157 μg+L-NAME+L-arginine), exhibited decreased haemorrhage and markedly counteracted thrombocytopenia.
CONCLUSIONS: L-NAME (thrombocytopenia), L-arginine (increased haemorrhage) counteraction and BPC 157 (decreased haemorrhage, counteracted thrombocytopenia) with rescue against two different anticoagulants, implicate a BPC 157 modulatory and balancing role with rescued NO-hemostatic mechanisms
Epicardial Adipose Tissue is Nonlinearly Related to Anthropometric Measures and Subcutaneous Adipose Tissue
No full textINTRODUCTION: Adipose tissue is the largest endocrine organ, composed of subcutaneous (SAT) and visceral adipose tissue (VAT), the latter being highly associated with coronary artery disease (CAD). Expansion of epicardial adipose tissue (EAT) is linked to CAD. One way of assessing the CAD risk is with low-cost anthropometric measures, although they are inaccurate and cannot discriminate between VAT and SAT. The aim of this study is to evaluate (1) the relationship between EAT thickness, SAT thickness and anthropometric measures in a cohort of patients assessed at the cardiology unit and (2) determine predictive power of anthropometric measures and EAT and SAT thickness in establishment of CAD.
METHODS: Anthropometric measures were obtained from 53 CAD and 42 non-CAD patients. Vascular and structural statuses were obtained with coronarography and echocardiography, as well as measurements of the EAT and SAT thickness.
RESULTS: Anthropometric measures showed moderate positive correlation with EAT and SAT thickness. Anthropometric measures and SAT follow nonlinear S curve relationship with EAT. Strong nonlinear power curve relationship was observed between EAT and SAT thinner than 10 mm. Anthropometric measures and EAT and SAT were poor predictors of CAD.
CONCLUSION: Anthropometric measures and SAT have nonlinear relationship with EAT. EAT thickness and anthropometric measures have similar CAD predictive value
Current Preventive Strategies and Management of Epstein-Barr Virus-related Post-transplant Lymphoproliferative Disease in Solid Organ Transplantation in Europe. Results of the ESGICH Questionnaire-based Cross-sectional Survey.
No full textThere is limited clinical evidence on the utility of the monitoring of Epstein-Barr virus (EBV) DNAemia in the pre-emptive management of post-transplant lymphoproliferative disease (PTLD) in solid organ transplant (SOT) recipients. We investigated current preventive measures against EBV-related PTLD through a web-based questionnaire sent to 669 SOT programmes in 35 European countries. This study was performed on behalf of the ESGICH study group from the European Society of Clinical Microbiology and Infectious Diseases. A total of 71 SOT programmes from 15 European countries participated in the study. EBV serostatus of the recipient is routinely obtained in 69/71 centres (97%) and 64 (90%) have access to EBV DNAemia assays. EBV monitoring is routinely used in 85.9% of the programmes and 77.4% reported performing pre-emptive treatment for patients with significant EBV DNAemia levels. Pre-emptive treatment for EBV DNAemia included reduction of immunosuppression in 50.9%, switch to mammalian target of rapamycin inhibitors in 30.9%, and use of rituximab in 14.5% of programmes. Imaging by whole-body 18-fluoro-deoxyglucose positron emission tomography (FDG-PET) is used in 60.9% of centres to rule out PTLD and complemented computer tomography is used in 50%. In 10.9% of centres, FDG-PET is included in the first-line diagnostic workup in patients with high-risk EBV DNAemia. Despite the lack of definitive evidence, EBV load measurements are frequently used in Europe to guide diagnostic workup and pre-emptive reduction of immunosuppression. We need prospective and controlled studies to define the impact of EBV monitoring in reducing the risk of PTLD in SOT recipients
Lysosomal Acid Lipase Deficiency in Children: our Experience and a Novel Possibility of Enzyme Replacement Therapy
No full textManjak lizosomske kisele lipaze autosomno je recesivno nasljedna bolest s dva klinička fenotipa. Wolmanova bolest počinje u ranoj dojenačkoj dobi i brzo je progresivna. Zbog masivnog nakupljanja kolesterolskih estera i triglicerida u crijevima, jetri, slezeni i drugim stanicama monocitno-makrofagnog reda dolazi do malapsorpcije, hepatosplenomegalije, zatajenja jetre i smrti u prvoj godini života. Bolest nakupljanja kolesterolskih estera može se očitovati od rane dječje do kasne odrasle dobi, varijabilna je tijeka i progresije. Glavna su obilježja različito izračena jetrena bolest, uključujući cirozu i zatajenje jetre, hiperkolesterolemija i rana ateroskleroza. Karakterističan je patohistološki nalaz mikrovezikularne steatoze i fibroze, a patognomoničan je ultrastrukturni nalaz kristala kolesterolskih estera. Dijagnozu potvr|uju mjerenje enzimske aktivnosti i/ili analiza gena. Liječenje je donedavno bilo suportivno i simptomatsko. Klinička istraživanja enzimskoga nadomjesnog liječenja pokazuju vrlo ohrabruju}e rezultate. Prikazujemo dojenče s Wolmanovom bolešću i dvoje djece s bolešću nakupljanja kolesterolskih estera s ciljem skretanja pozornosti na bolesti zbog manjka lizosomske kisele lipaze i što ranijeg početka optimalne skrbi.Lysosomal acid lipase deficiency is an autosomal recessive disorder with two distinct clinical phenotypes. Wolman disease is rapidly progressive with onset in early infancy. Complete enzyme deficiency results in massive accumulation of cholesterol esters and triglycerides in intestines, liver, spleen and other monocyte-macrophage system cells causing malabsorption, hepatosplenomegaly, liver failure and death in early infancy. Cholesterol ester storage disease may be diagnosed in childhood or later in life. It is characterized by chronic course and variable progression. Main features are variously expressed hepatopathy, including cirrhosis and liver failure, hypercholesterolemia and premature atherosclerosis. Characteristic is pathohistological finding of microvesicular steatosis and fibrosis and patognomonic are typical cholesterol ester crystals. Diagnosis is confirmed by enzyme assay and/or gene analysis. Until recently treatment was symptomatic. Ongoing clinical trials of enzyme replacement therapy have shown very promising results. We are presenting an infant with Wolman disease and two children with cholesterol ester storage disease with the aim to raise awareness about this disease and to start optimal care early
Sedmogodišnji trendovi u rezultatima hrvatske mreže primarne perkutane koronarne intervencije
No full textThe authors investigated trends in the Croatian primary Percutaneous Coronary Intervention (pPCI) Network results among three consecutive time intervals (2005-2007, first phase; 2008-2009, second phase; and 2010-2011, third phase). Data on 5650 patients with acute myocardial infarction with ST-elevation (STEMI ) transferred or directly admitted and treated with pPCI in 11 Croatian PCI centers during the study period were collected and analyzed. The number of patients with acute STEMI treated with pPCI per year rose continuously during the study period (581 vs.1272 vs. 1949 patients/year). The patient risk profile worsened during the study period: age (60 vs. 61 vs. 63 years; p<0.01), anterior myocardial wall involvement (43% vs. 44% vs. 51%; p<0.01), shock rate (7% vs. 9% vs. 11%; p<0.05), and percentage of transferred patients (42% vs. 36% vs. 46%; p<0.01). While the door-to-balloon time shortened (108 vs. 98 vs. 75 min; p<0.01), the symptom onset-to-door time increased (130 vs. 175 vs. 195 min; p<0.01), but without statistically significant influence on the total ischemic time. Multivariate log-linear analysis eliminated influence of a higher risk profile on the results of treatment and yielded no statistically significant changes in final TIMI 3 flow (Thrombolysis In Myocardial Infarction 3), in-hospital mortality, and six-month mortality rate, but revealed a significant increase in the rate of angina pectoris (12 vs. 22 vs. 36%; p<0.01) and other major adverse cardiovascular events (MACE; 6 vs. 23 vs. 14%; p<0.01) during follow up. In conclusion, the Croatian pPCI Network continuously ensures very good results of STEMI treatment in this economically less developed European country despite worsening of the risk profile in treated patients and opening of new, less experienced PCI centers. The higher percentage of MACE over time could be explained by changes in the pPCI strategy introduced over time (the culprit lesion only) and higher availability of PCI centers for additional PCI after acute STEMI. However, there is room for improvement, especially in reducing prehospital delay.Autori su istražili trendove u rezultatima Hrvatske mreže primarne perkutane koronarne intervencije (primary percutaneous coronary intervention, pPCI) između tri razdoblja (2005.-2007. (prva faza), 2008.-2009. (druga faza), 2010.-2011. (treća faza)). Prikupljeni su i izračunati podaci o 5650 bolesnika s akutnim infarktom sa ST-elevacijom (STEMI ) transportiranih ili izravno zaprimljenih i liječenih pomoću pPCI u 11 hrvatskih PCI centara tijekom toga vremena. Godišnji broj bolesnika s akutnim STEMI liječenih pomoću pPCI kontinuirano je rastao tijekom istraživanog vremena (581 prema 1272 prema 1949 bolesnika/godina). Rizični profil bolesnika se pogoršao kroz istraživano vrijeme: dob (60 prema 61 prema 63 godine; p<0,01), zahvaćanje prednje miokardijalne stijenke (43% prema 44% prema 51%; p<0,01), udio šoka (7% prema 9% prema 11%; p<0,05), postotak transportiranih bolesnika (42% prema 36% prema 46%; p<0,01). Dok se vrijeme od dolaska u bolnicu do uvođenja balona skraćivalo (108 prema 98 prema 75 min; p<0,01), vrijeme od nastupa simptoma do dolaska u bolnicu se produžavalo (130 prema 175 prema 195 min; p<0,01), ali bez statistički značajnog utjecaja na ukupno vrijeme ishemije. Multivarijatna log-linearna analiza, eliminirajući utjecaj višeg rizičnog profila na rezultate liječenja, nije pronašla statistički značajne promjene u završnom protoku TIMI 3 (Thrombolysis In Myocardial Infarction 3), bolničkom pobolu i smrtnosti tijekom šest mjeseci, ali je pokazala značajan porast učestalosti pektoralne angine (12% prema 22% prema 36%; p<0,01) i drugih velikih nepovoljnih kardiovaskularnih događaja (major adverse cardiovascular events, MACE) (6% prema 23% prema 14%; p<0,01) za vrijeme praćenja. Zaključno, Hrvatska mreža pPCI kontinuirano osigurava vrlo dobre rezultate liječenja STEMI u ovoj slabije razvijenoj zapadnoj zemlji unatoč pogoršanju rizičnog profila liječenih bolesnika, kao i otvaranju novih i manje iskusnih PCI centara. Povećanje postotka MACE može se objasniti promjenama u strategiji pPCI tijekom vremena (pPCI samo za ciljne lezije) i većom dostupnošću PCI centara za dodatnu PCI tijekom praćenja nakon akutnog STEMI . Ipak ima prostora za poboljšanje, osobito u skraćenju predbolničkog kašnjenja
Hyperbaric Oxygenation Modulates Vascular Reactivity to Angiotensin-(1-7) in Diabetic Rats: Potential Role of Epoxyeicosatrienoic Acids
No full textPreviously, a facilitating effect of hyperbaric oxygenation (HBO₂) on aortic ring responses to angiotensin-(1-7) in healthy rats was reported, with epoxyeicosatrienoic acids (EETs) possibly playing an important role. The aim of this study was to assess whether HBO₂ exerts similar effects in diabetic rats and to further explore the role of specific cytochrome P450 (CYP) enzymes in changes induced by HBO₂. Aortic relaxation to angiotensin-(1-7) was significantly higher in HBO₂ diabetic rats compared to control diabetic rats, while HBO₂ had no effect on angiotensin II contraction. N-methylsulphonyl-6-(2 propargyloxyphenyl /hexanamide inhibited the facilitation of angiotensin-(1-7) responses in HBO₂ rats, suggesting an important role of EETs in this modulation. mRNA expression of CYP2J3 and protein expression of CYP2C11 were significantly upregulated in HBO₂ diabetic rats, whereas CYP4A1, CYP4A2 and CYP4A3 mRNA and CYP2J3 protein expression was similar between groups. Mean arterial pressure, ferric reducing ability of plasma and Thiobarbituric Acid Reactive Substances levels and serum angiotensin-(1-7) concentrations were not significantly changed
Croatian guidelines for screening, prevention and treatment of protein-energy wasting in chronic kidney disease patients
No full textBolesnici s kroničnom bubrežnom bolesti imaju visoku stopu pobolijevanja i smrtnosti od srčano-žilnih bolesti kojoj u velikoj mjeri pridonosi i pothranjenost. Razvoju pothranjenosti pridonosi niz čimbenika rizika povezanih sa samom bubrežnom bolesti, ali i s nadomještanjem bubrežne funkcije dijalizom. Proteinsko-energijsku pothranjenost (PEP) potrebno je razlikovati od samog pojma pothranjenosti. Povezana je s upalom, trošenjem energijskih zaliha u mirovanju, niskim serumskim vrijednostima albumina i prealbumina, gubitkom mišićne mase s gubitkom tjelesne mase ili bez gubitka tjelesne mase te lošim kliničkim ishodom. Uključuje prehrambene i metaboličke poremećaje koji se javljaju u bolesnika s kroničnom bubrežnom bolešću, a dovode do razvoja stanja kroničnog katabolizma te gubitka mišićnog i masnog tkiva. Može biti prisutna i u adipoznih bolesnika, što se rijetko prepoznaje. Prevencija je najbolji pristup zbrinjavanju bolesnika. Potrebno je prepoznati bolesnike s povećanim rizikom od razvoja PEP-a i terapijski intervenirati. Prvi su koraci u liječenju nutritivno savjetovanje i promjene prehrambenih navika obavezno vodeći računa o unosu kuhinjske soli. Primjena enteralnih pripravaka sljedeći je korak u postizanju terapijskih nutritivnih ciljeva, nakon čega slijedi i intradijalitička parenteralna prehrana te u konačnici totalna parenteralna prehrana. Osim nutritivnih aspekata liječenja, nužno je istodobno liječiti i ostale probleme poput anemije, sekundarnog hiperparatiroidizma i acidoze uz osiguravanje odgovarajuće doze dijalize. Postizanje terapijskih ciljeva zahtijeva multidisciplinarni pristup, pri čemu se optimalni rezultati postižu suradnjom nefrologa, gastroenterologa i nutricionista.There is a high incidence of cardiovascular morbidity and mortality among patients with chronic kidney disease (CKD) and malnutrition is a powerful predictor of cardiovascular morbidity and mortality in this population of patients. A multitude of factors related to CKD and renal replacement therapy can affect the nutritional status of CKD patients and lead to the development of malnutrition. In patients with CKD, protein energy wasting (PEW) is a condition that is distinct from undernutrition and is associated with inflammation, increased resting energy expenditure, low serum levels of albumin and prealbumin, sarcopenia, weight loss and poor clinical outcomes. Nutritional and metabolic derangements are implicated for the development of PEW in CKD and leading to the development of chronic catabolic state with muscle and fat loss. Prevention is the best way in treating PEW. Appropriate management of CKD patients at risk for PEW requires a comprehensive combination of strategies to diminish protein and energy depletion, and to institute therapies that will avoid further losses. The mainstay of nutritional treatment in MHD patients is nutritional counselling and provision of an adequate amount of protein and energy, using oral supplementation as needed. Intradialytic parenteral nutrition and total enteral nutrition should be attempted in CKD patients who cannot use the gastrointestinal tract efficiently. Other strategies such as anemia correction, treatment of secondary hyperparathyroidism and acidosis, delivering adequate dialysis dose can be considered as complementary therapies in CKD patients. Multidisciplinary work of nephrologists, gastroenterologist and dietician is needed to achieve best therapeutic goals in treating CKD patients with PEW
The use of an Ultrasound-guided Supraclavicular Brachial Plexus Block in a high risk Patient with Cardiomyopathy
No full textWith the rapid growth of the elderly population, along with increased comorbidities and greater life expectancy, geriatric surgery has become more frequent and requires careful tailoring of anesthesia technique. Preanesthetic evaluation should concentrate on the identification of age-related diseases and an estimation of physiological reserve. Age-related cardiovascular changes are leading factors impacting perioperative outcomes among elderly patients. The management of a patient with dilated cardiomyopathy, who undergoes a non-cardiac surgery is always a challenge for an anesthesiologist,
as this situation is associated with a high mortality rate.
We report a use of the ultrasound guided supraclavicular brachial plexus block in 87-year old woman for revision of wound of left wrist and reposition and immobilization of left forearm and elbow. Her previous medical records revealed that she arterial hypertension, chronic atrial fibrillation with dilated cardiomyopathy and chronic kidney disease, stage II. Postoperatively, she developed respiratory insufficiency.
This case report exemplifies how despite all the measures and precaution we had taken, with choosing anesthesia having only minimal hemodynamic fluctuations and carefully planned and balanced hydration of patient we still had unwanted outcome
Myocardial fat as a part of Cardiac Visceral Adipose Tissue: Physiological and Pathophysiological view
No full textThoracic fat includes extra-pericardial (outside the visceral pericardium) and intra-pericardial (inside the visceral pericardium) adipose tissue. It is called ectopic adipose tissue although it is a normal anatomical structure. Intra-pericardial adipose tissue, which is predominantly composed of epicardial and pericoronary adipose tissue, has a significant role in cardiovascular system function. It provides metabolic-mechanical support to the heart and blood vessels in physiological conditions, while it represents metabolic-cardiovascular risk in case of qualitative and quantitative structural changes in the tissue: it correlates with coronary atherosclerotic disease, left ventricular mass, left atrium enlargement and atrial fibrillation presence. In the last decade there has been mounting evidence of fat cells presence in the myocardium of healthy (non-diseased) persons as well as in persons with both cardiovascular and non-cardiovascular diseases. Thus, it is necessary to clarify the incidence, aetiology, physiological role of fat cells in the myocardium, as well as the clinical significance of pathological fatty infiltration of the myocardiu
Adrenergic System Activation Mediates Changes in Cardiovascular and Psychomotoric Reactions in Young Individuals after Red Bull (©) Energy Drink Consumption.
No full textObjectives. To assess the effect of Red Bull© on (1) blood glucose and catecholamine levels, (2) cardiovascular and respiratory function changes before, during, and after exercise, (3) reaction time, (4) cognitive functions, and (5) response to mental stress test and emotions in young healthy individuals ( = 38).
Methods. Heart rate (HR) and arterial blood pressure (ABP), blood glucose, adrenaline, and noradrenalin plasma levels were measured before and after Red Bull© intake. Participants were subjected to 4 different study protocols by randomized order, before and 30 minutes after consumption of 500mL of Red Bull©.
Results. Mean ABP and HR were significantly increased at rest after Red Bull© intake. Blood glucose level and plasma catecholamine levels significantly increased after Red Bull© consumption. Heart rate, respiration rate, and respiratory flow rate were significantly increased during exercise after Red Bull© consumption compared to control condition. Intake of Red Bull© significantly improved reaction time, performance in immediate memory test, verbal fluency, and subject’s attention as well as performance in mental stress test.
Conclusion. This study demonstrated that Red Bull© has beneficial effect on some cognitive functions and effect on cardiovascular and respiratory system at rest and during exercise by increasing activity of the sympathetic nervous system