[Isolated Myocardial Infarction of the Right Ventricle Complicated by Myocardial Rupture with Cardiac Tamponade in a Female Patient with Arrhythmogenic Right Ventricular Dysplasia].

Arrhythmogenic dysplasia of the right ventricle is a rare pathology of the myocardium, the diagnosis of which is difficult. Isolated myocardial infarction of the right ventricle occurs and is diagnosed extremely rarely. In this article we describe a case of arrhythmogenic right ventricular dysplasia, complicated by transmural infarction of the anterolateral wall of the right ventricle, myocardial rupture, and cardiac tamponade.

[IDENTIFICATION OF OCCUPATIONAL RISK FOR ARTERIAL HYPERTENSION. REPORT II: ELIMINATION OF THE MODIFYNG INFLUENCE OF FACTORS OF CARDIOVASCULAR RISK].

This study is a continuation of (Report I) identification of the occupational risk of arterial hypertension (AH) in 13 occupational groups (3842 workers, men). In previous work there was eliminated the influence of traditional factors of the cardiovascular risk, in this study there was implemented the identification of the components of a healthy worker effect (HWE) and the elimination of their influence on the occupational risks of hypertension. Identification and removal of components HWE--the effect of a healthy recruitment (EHR) and the effect of the healthy worker persisting to work (EHWPW--was carried out by the analytic rearranging of the standardized for age and obesity prevalence rate of arterial hypertension with the use of own methodological approaches. For the determination of the presence and severity of EHR there was performed an analysis of the initial prevalence rate of arterial hypertension in the youngest age groups (under 31 years). To overcome HER standardized for age and obesity indices of the arterial hypertension prevalence rate were adjusted by the ratio of the frequency of arterial hypertension in the most young occupational and reference comparable groups. Identification of HWPW was executed by comparing the frequency of AH among workers retiring within 3 years from the occupational groups when compared to the whole sample. Then on the additional risk value there was adjusted the overall prevalence rate of AH in the occupation profession to overcome EHWPW. As a result of the consistent correction and elimination of the influence of HWE components on the prevalence rate of AH, there were obtained risks values, primarily reflecting the impact of occupational factors which can be considered as true occupational risks. Factors of the cardiovascular risk and HWE significantly modified true occupational risks for AH in a number of occupational groups up to inversion. At the same time, the pronouncement of EHR has a paramount importance in the modifying effect.

Investigation of bacterial inactivation in apheresis platelets with 24 or 30 hours between inoculation and inactivation.

BACKGROUND AND OBJECTIVES: Blood Centre logistics, staffing and donor scheduling may be optimized if pathogen inactivation (PI) of platelets can be delayed until Day 1, but bacteria may rapidly grow during this time. This study evaluates bacterial PI performed 24 and 30 h after collection. MATERIALS AND METHODS: PAS-3 platelet units were collected on the Amicus and subsequently inoculated (3-53 CFU/unit) with 1of 5 transfusion relevant bacterial species (n = 3/organism). Units were then stored for either 24 ± 0·3 or 30 ± 0·3 h at 20-24°C with agitation, subsequently treated with amotosalen and UVA, and stored for 7 days. Samples were taken before and after inactivation, on Days 2, 5 and 7 for BacT/ALERT testing, and on Days 5 and 7 for plate counts. RESULTS: All samples from units taken prior to inactivation either demonstrated positive plate culture counts, or, in untreated positive controls, were culture-positive during storage. All contaminated units treated with amotosalen and UVA 24 after inoculation were culture-negative on all days tested. With inactivation performed 30 h following inoculation, one of 15 units (1-of-3 replicates) was culture-positive with Klebsiella pneumonia (1 × 109 CFU/ml) by Day 5. CONCLUSION: Photochemical treatment did not inactivate 1 of 15 units to sterility in apheresis platelets stored in PAS with a 30-h delay between contamination and treatment, but did inactivate 15 of 15 units with a 24-h delay.

Amelioration of lesions associated with 24-hour suboptimal platelet storage at 16 °C by a p38MAPK inhibitor, VX-702.

BACKGROUND AND OBJECTIVES: Previous studies with p38MAPK inhibitors at room temperature demonstrated that they improve a large number of platelet storage parameters, but cannot substantially inhibit p38MAPK activation nor protect against widespread decrements in platelet quality parameters during 4 °C storage. In this study, platelet quality parameters and inhibition of p38MAPK by VX-702 were studied after incubation of platelets at 16 °C without agitation, suboptimal storage conditions which produce moderate platelet decrements. MATERIALS AND METHODS: Trima apheresis units were collected and aliquoted into three 60-ml CLX storage bags: (i) a control aliquot which was held at 20-24 °C with constant agitation; (ii) a test aliquot which was held at 20-24 °C with agitation until Day 2, when it was reincubated at 16 ± 1 °C for 24 ± 0·5 h without agitation and then returned 20-24 °C with agitation; (iii) a test aliquot containing 1 µm VX-702 stored in an identical fashion as aliquot 2. Aliquots were tested for an array of platelet storage parameters and p38MAPK activation on Days 1, 4 and 7. RESULTS: Many platelet storage parameters and p38MAPK activation were adversely affected by 24-h incubation at 16 °C without agitation. With the exception of ESC, addition of VX-702 prevented p38MAPK activation and the decrements in most observed parameters. CONCLUSION: Unlike 4 °C storage, VX-702 prevents activation of p38MAPK and decrements in many platelet storage parameters after exposure to 16 °C without agitation for 24 h.

Addition of sialidase or p38 MAPK inhibitors does not ameliorate decrements in platelet in vitro storage properties caused by 4 °C storage.

BACKGROUND AND OBJECTIVES: Bacterial proliferation is inhibited in platelets (PLTs) stored at refrigerated temperatures, but also dramatically decreases PLT in vivo survival. Recent studies have demonstrated that cold temperature (CT) stored PLTs secrete sialidases upon re-warming, removing sialic acid from the PLT surface, which may be responsible for clustering of GPIbα and PLT clearance from circulation. In this study, the influence of a sialidase inhibitor or a p38 MAP kinase inhibitor was evaluated in units stored at 4 °C. MATERIALS AND METHODS: After collection of a single Trima apheresis unit (n = 12), PLTs were aliquoted into four 60-ml CLX storage bags. One bag was stored at 20-24 °C (RT) with continuous agitation; a second bag was stored at 4 °C without agitation; a third bag was held at 4 °C without agitation with sialidase inhibitor, a fourth bag was incubated at 4 °C with a p38 MAPK inhibitor without agitation. RESULTS: Beginning from Day 1, all in vitro PLT parameters were adversely affected by CT compared to those of RT. Similar in vitro storage properties were observed in CT PLT in the presence or absence of sialidase or p38 MAPK inhibitors. P38 MAPK phosphorylation inhibition was not observed at CT. Decrease of sialidase activity was observed for 2 days in PLTs stored in additive solution but not in plasma. CONCLUSION: Addition of either sialidase or p38 MAPK inhibitors do not improve any in vitro parameters of PLTs stored at 4 °C in 100% plasma.

Evaluation of in vitro storage properties of apheresis platelets suspended in a bicarbonate-containing additive solution with low levels of plasma and stored with a 24-hour interruption of agitation.

BACKGROUND AND OBJECTIVES: PLT additive solutions (PAS) are useful for reducing the frequency and/or severity of plasma-associated transfusion reactions. A new PAS solution, PAS-5, containing 5% plasma, maintains in vitro PLT properties during 7-day storage. Periods with interruption of agitation (IA) ≤24 h routinely occur during PLT shipment and do not usually compromise platelet quality. The aim of the study was to evaluate the properties of PLTs stored for 7 days in 95% PAS-5/5% plasma subjected to a 24-h IA. MATERIALS AND METHODS: Double apheresis Amicus units (n = 12) were collected using a manual PAS-5 addition to hyperconcentrated PLTs. PLT units were equally divided in two containers. Control and test PLTs were stored with continuous agitation at 20-24°C except for 24-h IA period for test units between days 2-3. RESULTS: During storage, levels of glucose, lactate, mitochondrial membrane potential and aggregation significantly differed in test units compared to those of control. The pH levels of test PLTs were less than those of control units with 7/12 test units having pHs <6·2 on Day 7 compared to 1/12 control units. Morphology score, GP1bα expression, ESC values, superoxide production were also less, and activation was greater in test PLTs than those of control. All other parameters were similar between test and control units. CONCLUSION: PLTs stored in PAS-5 solution containing 5% plasma with a 24-h IA results in marked decrements in many in vitro PLT quality parameters during 7-day storage.

[The dependence of the prevalence of hypertension on the severity of the professional aging].

On the example of 5437 employees of enterprises and institutions of the Kemerovo region, compiled into 14 occupational groups, an analysis of the relationship between age structure and the frequency of arterial hypertension due to the working conditions has been performed At high levels of hardness of employment and the impact of physical factors, a shift in the age structure toward younger age is seen, which is considered as a demographic consequence of professional ageing. In turn, expressed professional ageing causes the reduction in the prevalence of hypertension, which is, probably is implemented by the effect of "healthy worker".

[The environment as a risk factor of coronary heart disease in urbanized region with developed chemical industry].

Tendency to growth of prevalence of ischemic heart disease (IHD) occurring in Russian Federation despite application of preventive measures designates necessity of search for novel nontraditional factors of risk. Among other studied factors of genesis of cardiovascular diseases in general and of IHD in particular is the role of xenobiotics - chemical pollutants, substances foreign to the body. In this paper we present results of a number of epidemiological studies on the problem of xenobiotics and IHD. Special attention is given to the difficulty of isolation of the leading chemical pollutant and as a consequence of pathogenetic link what leads to underestimation of pathological states caused by ecological factors especially in such urbanized region with developed chemical industry as Kusbass.

[Work intensity and arterial hypertension].

The authors presented dependence of arterial hypertension on work intensity, exemplified by two occupational groups--teachers and electricians, and demonstrated modifying influence of occupation on prevalence of traditional cardiovascular risk factors.

[Risks of development of arterial hypertension in occupational groups of Western Siberia: comparison with national representative data].

Risk analysis of development of arterial hypertension in 14 occupational groups of Western Siberia (4472 workers) is carried out. As a reference group the all-Russian data on prevalence of arterial hypertension by results of the second stage of monitoring of an epidemiological situation on arterial hypertension in the Russian Federation (2005-2007) were used. Paid off the odds ratio and 95% a confidential interval. The obtained data allowed to characterize occupational distinctions of risk of development of arterial hypertension and to allocate occupational groups of Western Siberia with high level of arterial hypertension. Results of research testifies to need of consideration of healthy worker effect as the factor of formation of frequency of arterial hypertension connected with a profession in occupational groups.

In vivo recovery and survival of red cells after photodynamic treatment with thiopyrylium and red light using a canine model.

Recently, we have shown that thiopyrylium has robust inactivation capabilities against a broad spectrum of pathogens in the human red blood cell (RBC) suspensions while retaining key RBC in vitro properties. The 24-h recovery and survival of canine red cells were measured upon autologus reinfusion of control and phototreated units. The 24-h recovery of control and phototreated RBCs was 75.7 +/- 6.4% and 87.5 +/- 8.5%, respectively. The time for 50% survival of labelled control RBCs was similar to that of phototreated group (206 +/- 58 h vs. 255 +/- 63 h, respectively). Results suggest that thiopyrylium phototreatment does not negatively affect canine RBC in vivo recovery.

Photoinactivation of Leishmania donovani infantum in red cell suspensions by a flexible thiopyrylium sensitizer.

BACKGROUND AND OBJECTIVES: Leishmaniasis is a disease caused by protozoan parasites of the genus Leishmania, which are intracellular parasites of monocytes and macrophages. Transmission of the organism has been observed by transfusion of infected blood from asymptomatic donors to immunocompromised recipients, leading to clinically apparent disease. There is no licensed Leishmania screening test currently available. MATERIALS AND METHODS: This study investigated the potential for a novel DNA-intercalating photosensitizer, thiopyrylium (TP), to inactivate Leishmania donovani infantum in red cell (RBC) suspensions. RESULTS: A 5.7 TCID50 reduction of Leishmania was observed in samples treated with 12.5 micromole l(-1) TP and 1.1 J cm(-2) light. CONCLUSIONS: Leishmania is highly sensitive to photoinactivation under conditions that have been previously demonstrated to maintain RBC properties during 42 days of storage.

Investigation of photosensitizing dyes for pathogen reduction in red cell suspensions.

Despite recent advances in blood safety by careful donor selection and implementation of infectious disease testing, transmission of viruses, bacteria and parasites by transfusion can still rarely occur. One approach to reduce the residual risk from currently tested pathogens and to protect against the emergence of new ones is to investigate methods for pathogen inactivation. The use of photosensitizing dyes for pathogen inactivation has been studied in both red cell and platelet blood components. Optimal properties of sensitizing dyes for use in red cell suspensions include selection of dyes that traverse cell and viral membranes, bind to nucleic acids, absorb light in the red region of the spectrum, inactivate a wide range of pathogens, produce little red cell photodamage from dye not bound to nucleic acid and do not hemolyze red cells in the dark. Early research at the American Red Cross focused on the use of a class of dyes with rigid structures, such as the phenothiazine dyes, beginning with the prototypical sensitizer methylene blue. Results revealed that methylene blue phototreatment could inactivate extracellular virus, but resulted in undesirable defects in the red cell membrane that resulted in enhanced hemolysis that became evident during extended refrigerated blood storage. In addition, methylene blue phototreatment could neither inactivate intracellular viruses nor appreciably inactivate bacteria under conditions of extracellualar viral killing. Attempts to improve intracellular viral inactivation led to the investigations of more hydrophobic phenothiazines, such as methylene violet or dimethylmethylene blue. Although these dyes could inactivate intracellular virus, problems with increased red cell membrane damage and hemolysis persisted or increased. Further studies using red cell additive storage solutions containing high levels of the impermeable ion, citrate, to protect against colloidal osmotic hemolysis as well as competitive inhibitors to limit sensitizer binding to red cell membranes revealed that photoinduced hemolysis stemmed from dye bound to the red cell membrane as well as dye free in solution. Use of red cell additive solutions to prevent colloidal-osmotic hemolysis and use of novel flexible dyes that only act as sensitizers when bound to their targets are two techniques that currently are under investigation for reducing red cell damage. Ultimately, the decision to implement a photodynamic method for pathogen reduction will be determined by weighing the risks of unintended adverse consequences of the procedure itself, such as the potential for genotoxicity and allergic reactions, against the cost and benefits of its implementation.

Duck hepatitis B photoinactivation bydimethylmethylene blue in RBC suspensions.

BACKGROUND: Dimethylmethylene blue (DMMB) has been used to photoinactivate a number of model viruses, including VSV, in RBC suspensions under conditions that preserve in vitro RBC properties during storage. The relative sensitivity of duck HBV (DHBV) and VSV to photoinactivation by DMMB was investigated by performing an indirect immunofluorescence assay (IFA) using primary duck hepatocyte (PDH) cultures or a standard plaque assay for the respective viruses. STUDY DESIGN AND METHODS: DMMB was added to 45-percent Hct, WBC-reduced, oxygenated AS-3 RBCs at 10-, 1-, and 0.1-microM concentrations. Samples (1-mm thick) were illuminated with 5.4-mW per cm(2) of red light for 2 or 9 seconds. Unilluminated samples without DMMB or with 10 microM DMMB served as control. RESULTS: DHBV and VSV were rapidly photoinactivated by DMMB in a concentration and light-dose-dependent fashion. Neither virus was substantially inactivated by incubation with DMMB in the dark. For a given light exposure, DHBV required a concentration of DMMB one-one hundredth that of VSV to achieve approximately the same level of inactivation. CONCLUSION: DHBV appears to be considerably more sensitive than VSV to DMMB photoinactivation. Photoinactivation in 45-percent Hct RBCs can be achieved in seconds by using micromolar quantities of dye.

Inactivation of WBCs in RBC suspensions by photoactive phenothiazine dyes: comparison of dimethylmethylene blue and MB.

BACKGROUND: The transfusion of blood components containing WBCs can cause unwanted complications, which include virus transmission, transfusion-associated GVHD, alloimmunization, febrile reactions, and immunomodulation. Phototreatment with 4 microM of dimethylmethylene blue (DMMB) and 13 J per cm(2) of white light irradiation has previously been shown to be an effective way to inactivate different models of enveloped and nonenveloped viruses in RBC suspensions, with minimum damage to RBCs. The present study compares WBC photoinactivation in buffy coat after DMMB or MB phototreatment under virucidal conditions. STUDY DESIGN AND METHODS: Buffy coat diluted to 30-percent Hct was treated with the dye and white light. Isolated WBCs were assayed for cell proliferation and viability by an assay using a tetrazolium compound, limiting dilution analysis, DNA fragmentation, and flow cytometry assays. RESULTS: DMMB and 2.5 J per cm(2) of light phototreatment can inactivate T cells to the limit of detection by limiting dilution analysis (>4.76 log reduction). No WBC proliferation activity was observed after DMMB and 3.8 J per cm(2) of light. DNA degradation after DMMB phototreatment was light dependent. In addition, DMMB phototreatment induced apoptosis in WBCs. In contrast, MB phototreatment under virucidal conditions did not cause significant changes in the viability of WBCs. Neither DNA degradation nor signs of apoptosis were observed after MB phototreatment. CONCLUSION: DMMB phototreatment inactivates T-lymphocytes, the cells that cause GVHD.

The use of dimethylmethylene blue for virus photoinactivation of red cell suspensions.

Phenothiazine dyes and light have been known to have virucidal properties for over seventy years. This review will describe recent progress in the use of one phenothiazine dye, dimethyl-methylene blue, for photo-inactivation of a number of RNA and DNA viruses in red cell suspensions under conditions that minimally affect red cell in vitro properties during 42-day 1-6 degrees C storage. Dimethylmethylene blue has a higher affinity for nucleic acid than the closely related phenothiazine, methylene blue. Virus photoinactivation appears to be mediated by singlet oxygen. The kinetics of photoinactivation depends on the virus studied, but for a given virus, is similar for both intracellular and extracellular forms. The similarity for inactivation of intracellular and extracellular virus suggests that a common target, such as nucleic acid, is involved. Finally, lymphocytes, which can harbour transfusion-associated viruses and can mediate transfusion-associated-graft-versus host disease, are sensitive to dimethylmethylene blue photoinactivation under virucidal conditions.

Preservation of red cell properties after virucidal phototreatment with dimethylmethylene blue.

BACKGROUND: All published reports have described methods for virus photoinactivation which significantly alter red cell (RBC) properties during storage. In order to improve virucidal activity and reduce damage to RBCs, a series of phenothiazine derivatives were either synthesized or purified and screened for bacteriophage inactivation and red cell potassium efflux. One compound, 1,9-dimethylmethylene blue (dimethyl-methylene blue), had superior screening results and was chosen for further characterization. STUDY DESIGN AND METHODS: White cell reduced RBC suspensions (30% hematocrit) were deliberately inoculated with extracellular virus or virus-infected VERO cells, incubated with 4 microM dimethyl-methylene blue and illuminated with cool-white fluorescent light. Control and treated samples were titered for virus inactivation. In parallel studies, RBC suspensions were exposed to dimethylmethylene blue and light under identical conditions and assayed for in vitro RBC storage properties. RESULTS: Phototreatment of RBC suspensions inactivated > 4.4 log10 of extracellular vesicular stomatitis virus (VSV), > 3.0 log10 of intracellular VSV, > 5.0 log10 of extracellular pseudorabies virus (PRV), > 4.8 log10 of intracellular PRV, > 4.7 log10 of extra-cellular bovine virus diarrhea virus, 5.8 log10 of bacterio-phage phi 6 and > 7 log10 of bacteriophage R17. Encephalo-myocarditis virus, a nonenveloped picornavirus, was resistant to photoinactivation. Virucidal conditions resulted in no detectable IgG binding in 11 of 13 samples, unchanged RBC morphology, normal banding patterns of RBC membrane proteins on SDS PAGE, and unaltered characteristics of 12 of 13 RBC antigens during storage as measured by antibody titrations. In addition, minimal changes were observed in RBC osmotic fragility, lysis, potassium efflux, ATP and 2,3-DPG levels, and the strength of one RBC antigen during storage of phototreated samples compared with controls. CONCLUSION: Dimethylmethylene blue photo-treatment can inactivate several intracellular and extracellular model viruses under conditions which minimally alter RBC properties during 42 days storage at 1-6 degrees C.

Factors affecting virus photoinactivation by a series of phenothiazine dyes.

A series of four phenothiazine dyes, including methylene blue (MB), were previously tested for their ability to photoinactivate viruses in red cell suspensions. One of the dyes, 1,9-dimethyl-3-dimethylamino-7-dimethylaminophenothiazine (1,9-dimethylmethylene blue), exhibited good intracellular and extracellular virucidal activity for several RNA and DNA viruses under conditions that minimally affected red cell properties. In order to understand why the virucidal specificity of 1,9-dimethylmethylene blue was greater than other phenothiazines tested, the physical and chemical properties of the dye were compared to three other closely related analogues (MB, 1,9-dimethyl-3-diethylamino-7-dibutylaminophenothiazine [compound 4-140], 1,9-dimethyl-3-dimethylamino-7-diethylaminophenothiazine [compound 6-136]). All compounds required light and oxygen for virucidal activity and had relatively high singlet oxygen yields (> 0.5), but 1,9-dimethylmethylene blue had a singlet oxygen yield approximately 50% greater than that of MB. In addition, the hydrophobicity/hydophilicity of the compounds varied, with the partition coefficients (2-octanol : water) ranging from 0.11 for MB to 3560 for compound 4-140. The dyes had the following affinities for DNA: 1,9-dimethylmethylene blue > compound 6-136 > MB approximately compound 4-140. This order was similar to the order of activities for photoinactivation of the nonenveloped bacteriophage, R17, by the four compounds. Results with the most hydrophobic compound, 4-140, contrasted with those obtained with 1,9-dimethylmethylene blue. Compound 4-140 had a high affinity for protein and a low affinity for DNA. Although compound 4-140 and light inactivated the nonenveloped bacteriophage R17 poorly, the dye readily photoinactivated enveloped viruses in buffer. However, unlike results with 1,9-dimethylmethylene blue, viral inactivation of enveloped viruses by compound 4-140 was completely inhibited by the presence of red cells and plasma. Thus, the high affinity of 1,9-dimethylmethylene blue for DNA and the dye's efficient singlet oxygen yield suggest viral nucleic acid as a potential target, which could explain the photosensitizer's ability to inactivate viruses without adversely affecting anucleate red cells.

Comparison of methylene blue and methylene violet for photoinactivation of intracellular and extracellular virus in red cell suspensions.

Previous studies with methylene blue (MB) in red cell suspensions have demonstrated that extracellular, but not intracellular, virus can be readily photoinactivated. To test if the resistance of intracellular virus to inactivation is related to the permanent positive charge of the phenothiazine, a series of uncharged phenothiazine dyes, methylene violet (MV), monodemethylated MV and didemethylated MV, were studied. Values of the sensitivity of intracellular relative to extracellular vesicular stomatitis virus (VSV) inactivation for the three dyes (D10 extracellular/D10 intracellular) in buffer were 1.0, 0.60 and 0.33, respectively. In contrast, intracellular virus was resistant to inactivation with MB, with a D10 extracellular/D10 intracellular of 0.05 in buffer. Because virucidal activity of MV was inhibited by the presence of plasma, the red cells (30% hematocrit) were repeatedly washed prior to photoinactivation and storage. Under conditions where MB and MV inactivated approximately 5 log10 of extracellular VSV, intracellular VSV was inactivated by more than 4 log10 with MV compared to 0.88 log10 with MB. These phototreatment conditions did not significantly affect red cell morphology, extracellular pH, ATP or 2,3-diphosphoglycerol levels during 42 days of 1-6 degrees C storage. There was enhanced potassium efflux and hemolysis over values obtained from untreated control; the extent of change from controls was comparable for each phototreatment. These results indicate that the uncharged phenothiazine dye, MV, can inactivate both intracellular and extracellular virus yet exhibit similar in vitro red cell storage properties as MB phototreatment.