Acute systemic inflammatory response after cardiac surgery in patients infected with human immunodeficiency virus using clinical and inflammatory markers

Background: Immediate post-cardiopulmonary bypass (CPB) immune responses and organ injuries in immune-compromised patients remain poorly documented.Method: Sixty-one consecutive patients (30 HIV seropositive and 31 seronegative), undergoing elective cardiac valve(s) replacement were enrolled, from a single center hospital, after informed consent was obtained. C-reactive protein (CRP) and Erythrocyte sedimentation rate (ESR) were used as biomarkers of acute inflammatory response.Results: The mean age was similar between the HIV seropositive and negative group. Pre-operatively, CRP (p=0.388) and ESR (p=0.817) were comparable. The CPB events and durations were significantly different between the two groups: duration (p=0.021), clamp aortic duration (p=0.026), bloodtransfusion (p=0.013), total urine output (p=0.035) and peak lactate (p=0.040). Post-operatively, there was significant increased biomarkers level in both groups, albeit not between the groups with a significant negative correlation between the mean change in CRP levels and mechanical ventilation (r=0.548, p=0.002) in the seropositive group (r=0.025, p=0.893). The correlation between pre-operative and post-operative difference in CRP and ICU stay was not significant in both groups. A significant drop (p=<0.001) in CD4 cells was documented post-operatively in the HIV seropositive group.Conclusion: HIV positive patients’ post-operative reactions to cardiac surgery supported by CPB are similar to those of HIV seronegative patients.Keywords: Cardiopulmonary bypass (CPB), Human immunodeficiency virus (HIV), inflammatio

The influence of drug interactions on the international Normalized Ratio (INR) in hospitalized patients on warfarin therapy

Interakcije lijekova predstavljaju značajno područje istraživanja u suvremenoj medicini. Varfarin kao temeljni lijek pri liječenju i prevenciji duboke venske tromboze, plućne embolije i drugih bolesti, zbog svoje specifične građe, biotransformacije, metabolizma, individualnog doziranja i opasnosti od krvarenja predstavlja trajni izazov. U svrhu pokušaja evaluacije utjecaja interakcija lijekova na međunarodni normalizirani omjer (INR) kao temeljni parametar praćenja terapije varfarinom, tijekom ovog istraživanja je korišten računalni program za probir interakcija Lexi-Interact. U radu je provedena analiza 339 bolesnika kojima je tijekom hospitalizacije započeta terapija varfarinom, te su temeljem programa podijeljeni u ispitnu skupinu (223 bolesnika) sa mogućim klinički značajnim interakcijama s varfarinom i kontrolnu skupinu (116 bolesnika) bez njih. Bolesnici su u prosjeku istodobno dobivali 5,28 lijekova (od 1-13 lijekova po bolesniku). Analizom rezultata vidljivo je da je 65,8% bolesnika bilo izloženo klinički značajnim interakcijama (1-6 interakcija po bolesniku). Statistički značajna razlika između navedene dvije skupine zabilježena je samo u broju lijekova, izuzev varfarina, kojima su bolesnici bili liječeni. Interakcije nisu statistički značajno utjecale na vrijednosti INR-a sedmog dana terapije, kao ni na visinu doze varfarina istog dana. Značajan utjecaj interakcija nije zabilježen pri podjeli bolesnika na podskupine s ciljnim INR između 2 i 3, te one iznad i ispod tih vrijednosti, kao niti na učestalost zabilježenih nuspojava. Zaključno, ovim istraživanjem nije dokazan utjecaj interakcija varfarina s drugim lijekovima na međunarodni normalizirani omjer, te individualno titriranje i praćenje ostaje temelj njegova uvođenja u terapiju.Drug interactions represent an important area of research in modern medicine. Warfarin, as the basic drug for treatment and prevention of deep venous thrombosis, pulmonary embolism and other diseases, due to its specific composition, biotransformation, metabolism, individual dosing and the risk of bleeding represents a permanent challenge. In the attempt to evaluate the influence of drug interactions on the International Normalized Ratio (INR), the computer program for screening drug interactions called Lexi- Interact was used during this research as the basic parameter for monitoring warfarin therapy. In this paper, the analysis of 339 patients whose warfarin therapy began during hospitalization was conducted. Based on the program, they were divided into the group with (223 patients), and the group without (116 patients) possible clinically significant interactions. On the average, the patients were concurrently taking 5.28 drugs (1-13 drugs per patient). The analysis of results shows that 65.8% of patients were exposed to clinically significant interactions (1-6 interactions per patient). Statistically significant difference between the two groups was recorded only in the number of drugs, apart from warfarin, the patients were treated with. The interactions did not have a statistically significant impact on the INR values on the day 7 of therapy or on the dose of warfarin on the same day. A significant influence of interactions was not recorded in the division of patients into subgroups with target INR between 2 and 3, and those above and under those values; or on the frequency of recorded side-effects. In conclusion, this research did not prove the influence of warfarin interactions with other drugs on the International Normalized Ratio, and therefore individual titration and monitoring remains the basis of its introduction into therapy

Acute systemic inflammatory response after cardiac surgery in patients infected with human immunodeficiency virus using clinical and inflammatory markers.

Background: Immediate post-cardiopulmonary bypass (CPB) immune responses and organ injuries in immune-compromised patients remain poorly documented. Method: Sixty-one consecutive patients (30 HIV seropositive and 31 seronegative), undergoing elective cardiac valve(s) replacement were enrolled, from a single center hospital, after informed consent was obtained. C-reactive protein (CRP) and Erythrocyte sedimentation rate (ESR) were used as biomarkers of acute inflammatory response. Results: The mean age was similar between the HIV seropositive and negative group. Pre-operatively, CRP (p=0.388) and ESR (p=0.817) were comparable. The CPB events and durations were significantly different between the two groups: duration (p=0.021), clamp aortic duration (p=0.026), bloodtransfusion (p=0.013), total urine output (p=0.035) and peak lactate (p=0.040). Post-operatively, there was significant increased biomarkers level in both groups, albeit not between the groups with a significant negative correlation between the mean change in CRP levels and mechanical ventilation (r=0.548, p=0.002) in the seropositive group (r=0.025, p=0.893). The correlation between pre-operative and post-operative difference in CRP and ICU stay was not significant in both groups. A significant drop (p=<0.001) in CD4 cells was documented post-operatively in the HIV seropositive group. Conclusion: HIV positive patients\u2019 post-operative reactions to cardiac surgery supported by CPB are similar to those of HIV seronegative patients

Transplantation of genetically marked cardiac muscle cells

AbstractWe examined the possibility that cardiomyocytes could be genetically marked or modified before being grafted to the heart under conditions applicable to the clinical setting. We used a replication-defective recombinant adenovirus carrying the β-galactosidase reporter gene, and delivered it to cultured murine fetal cardiac myocytes. Virtually all fetal cardiomyocytes in a primary culture expressed β-galactosidase 24 hours after recombinant adenovirus infection. These cells were transplanted to the hearts of syngenic adult recipient mice. Expression of the β-galactosidase gene in the grafted cells was demonstrated by staining with 5-bromo-4-chloro-3-indoyl-β-d-galactosidase, resulting in a blue color at the histochemical level and an electron-dense deposit on transmission electron microscopic analysis. Gene expression was recognized from 7 days to 12 weeks after transplantation. Implanted cardiomyocytes aligned themselves along the layers of the host myocardium. Formation of gap junctions was demonstrated by transmission electron microscopy. Neither inflammation nor fibrous scar tissue was detectable by histologic analysis. This study demonstrates that ex vivo gene transfer to the heart by means of the adenoviral vector is possible. (J Thorac Cardiovasc Surg 1997;113:10-8

Određivanje područja odgovarajućih gustoća kod primjene kompenzacije crne za izabrani profil

In standard graphic reproduction subtractive system of process inks coverage is observed. For achieving wider reproduction range, as well as higher density, additional black printer is added into printing system. Today graphic arts ISO specification routes defined overall coverage, meaning also black compensation principles. Although, the theoretical substitution of chromatic part of process inks with black can be very high, practical results can render certain misalignments in neutral as well as other tertiary colours, not achieving predicted values. That maintains the demand of additional customization of reproduction for certain images to preserve reproduction quality. A test target proof and soft proof are considered for proposed profiles, including adequate equivalent densities or lightness.U standardnoj grafičkoj reprodukciji promatra se subtraktivni sustav procesnog miješanja boja i pokrivenost bojama. Kako bi se postignuo veći raspon reprodukcije tonova kao i veće zacrnjenje, dodatni crni izvadak se ugrađuje u reprodukcijski sustav. Današnje ISO specofikacije za grafičku reprodukciju preporučaju određenu ukupnu pokrivenost, uključujući principe kompenzacije crne boje. Iako zamjena kromatskog dijela procesnih boja sa crnom može biti vrlo velika, praktični rezultati mogu voditi određenom odstupanju kod neutralnih kao i tercijarnih boja. To upućuje na potrebu dodatne prilagodbe za određene slike kako bi se osigurala kvaliteta reprodukcije. Testna karta je reproducirana kao ekranska i otisnuta za izabrani profil, gdje su postignute odgovarajuće ujednačene gustoće

TAT-dextran-mediated mitochondrial transfer enhances recovery from models of reperfusion injury in cultured cardiomyocytes

Acute myocardial infarction is a leading cause of death among single organ diseases. Despite successful reperfusion therapy, ischaemia reperfusion injury (IRI) can induce oxidative stress (OS), cardiomyocyte apoptosis, autophagy and release of inflammatory cytokines, resulting in increased infarct size. In IRI, mitochondrial dysfunction is a key factor, which involves the production of reactive oxygen species, activation of inflammatory signalling cascades or innate immune responses, and apoptosis. Therefore, intercellular mitochondrial transfer could be considered as a promising treatment strategy for ischaemic heart disease. However, low transfer efficiency is a challenge in clinical settings. We previously reported uptake of isolated exogenous mitochondria into cultured cells through co-incubation, mediated by macropinocytosis. Here, we report the use of transactivator of transcription dextran complexes (TAT-dextran) to enhance cellular uptake of exogenous mitochondria and improve the protective effect of mitochondrial replenishment in neonatal rat cardiomyocytes (NRCMs) against OS. TAT-dextran-modified mitochondria (TAT-Mito) showed a significantly higher level of cellular uptake. Mitochondrial transfer into NRCMs resulted in anti-apoptotic capability and prevented the suppression of oxidative phosphorylation in mitochondria after OS. Furthermore, TAT-Mito significantly reduced the apoptotic rates of cardiomyocytes after OS, compared to simple mitochondrial transfer. These results indicate the potential of mitochondrial replenishment therapy in OS-induced myocardial IRI

Host-directed therapy for bacterial infections -Modulation of the phagolysosome pathway-

Bacterial infections still impose a significant burden on humanity, even though antimicrobial agents have long since been developed. In addition to individual severe infections, the f fatality rate of sepsis remains high, and the threat of antimicrobial-resistant bacteria grows with time, putting us at inferiority. Although tremendous resources have been devoted to the development of antimicrobial agents, we have yet to recover from the lost ground we have been driven into. Looking back at the evolution of treatment for cancer, which, like infectious diseases, has the similarity that host immunity eliminates the lesion, the development of drugs to eliminate the tumor itself has shifted from a single-minded focus on drug development to the establishment of a treatment strategy in which the de-suppression of host immunity is another pillar of treatment. In infectious diseases, on the other hand, the development of therapies that strengthen and support the immune system has only just begun. Among innate immunity, the first line of defense that bacteria encounter after invading the host, the molecular mechanisms of the phagolysosome pathway, which begins with phagocytosis to fusion with lysosome, have been elucidated in detail. Bacteria have a large number of strategies to escape and survive the pathway. Although the full picture is still unfathomable, the molecular mechanisms have been elucidated for some of them, providing sufficient clues for intervention. In this article, we review the host defense mechanisms and bacterial evasion mechanisms and discuss the possibility of host-directed therapy for bacterial infection by intervening in the phagolysosome pathway

Myeloid sarcomas: a histologic, immunohistochemical, and cytogenetic study

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A phase 1 clinical trial of vorinostat in combination with decitabine in patients with acute myeloid leukaemia or myelodysplastic syndrome

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108599/1/bjh13016.pd