Comparison and optimization of randomly textured surfaces in thin-film solar cells.

Using rigorous diffraction theory we investigate the scattering properties of various random textures currently used for photon management in thin-film solar cells. We relate the haze and the angularly resolved scattering function of these cells to the enhancement of light absorption. A simple criterion is derived that provides an explanation why certain textures operate more beneficially than others. Using this criterion we propose a generic surface profile that outperforms the available substrates. This work facilitates the understanding of the effect of randomly textured surfaces and provides guidelines towards their optimization.

High prevalence of IgE antibodies among blood donors in Sweden and Norway.

BACKGROUND: Reactions after a blood transfusion could be allergic because of passive transfer of immunoglobulin E (IgE) antibodies from allergic donors. AIMS OF THE STUDY: To compare spectrum and prevalence of IgE antibodies in blood donors from Sweden and Norway. METHODS: Using the ImmunoCAP method, serum samples from 1002 blood donors from Sweden and 500 from Norway were analysed for IgE antibodies to common inhalant and food allergens and allergens common in a hospital environment, such as penicilloyl G and latex. RESULTS: As many as 23.6-27.3% of the donors had IgE antibodies to at least one of the 14 allergens tested. Of these 6.8-16.7% had extremely high concentrations, i.e. >35 kU(A)/l corresponding to 100 times the cut-off for a positive allergy test. Most donors were sensitized to pollens, dander and mite but several had very high levels of IgE antibodies to penicilloyl G, latex and peanut. The pattern of sensitizing allergens differed between Sweden and Norway. CONCLUSIONS: High serum levels of IgE antibodies to various allergens are common among blood donors and the degree of sensitization and spectrum of involved allergen varies between geographical regions. Present routines to identify IgE sensitized, potential risk, donors are not satisfactory; the sensitivity of selection procedures is about 25%.

Occurrence of cold activation of transfusion plasma during storage at +4 degrees C.

BACKGROUND AND OBJECTIVES: The storage of transfusion plasma at +4 degrees C sometimes leads to the activation of several proteolytic systems. In this study the frequency of cold activation was investigated, as well as whether cold activation of plasma is an individually recurrent property of the donor. MATERIALS AND METHODS: Plasma units prepared from whole blood obtained from 100 male donors were stored at +2 degrees to +5 degrees C, in bags for 28 days and in cryotubes for up to 42 days. Samples from plasma units, collected by apheresis from 100 male donors, were stored in cryotubes for up to 42 days. Cold activation was measured weekly as kallikrein-like activity of plasma. Samples from repeat apheresis plasma units from 32 donors were measured 12-20 months later. The effects of storage on the contact, coagulation and fibrinolytic systems were determined. RESULTS: The cumulative frequency of cold-activated plasma units stored in bags was 5% on day 7 and 18% on day 28. After 42 days in cryotubes, 49% of the plasma units were cold activated. Large intraindividual differences in the onset-day of cold activation were observed in plasma samples of some donors. During cold activation, an increase in kallikrein-like activity was accompanied by a decrease in C1 esterase inhibitor activity and an increase in the concentrations of activated factor VII and fibrinopeptide A. The functional plasminogen level was unchanged, while a minor decrease in plasmin inhibitor activity was combined with a corresponding increase in the concentration of plasmin-plasmin inhibitor complex. CONCLUSIONS: The cumulative frequency of cold-activated plasma units increased in a time-dependent manner during storage at +2 degrees to +5 degrees C for 42 days. The intraindividual onset-day of cold activation varied widely between plasma samples of some donors. Cold activation was associated with a high degree of activation of the contact and coagulation systems. The fibrinolytic system was scarcely affected.

Nicotinamide inhibits endotoxin-induced monocyte tissue factor expression.

BACKGROUND: Tissue factor (TF) is the main initiator of blood coagulation in vivo. Its increased expression on activated monocytes is associated with thrombotic complications and mortality in conditions such as sepsis, disseminated intravascular coagulation and coronary artery disease. OBJECTIVE: The effect of the vitamin B derivative nicotinamide on endotoxin-induced monocyte TF and CD11b expression, soluble interleukin(IL)-6, and clotting onset time (COT) was studied. METHODS: Experiments were conducted in human peripheral blood leukocyte suspensions and in whole blood from eight healthy volunteers. Free oscillating rheometry (measuring COT) and flow cytometry were applied to evaluate the effect of endotoxin on TF, CD11b, IL-6 and the overall coagulation response of plasma supplemented with activated autologous leukocytes. RESULTS: In response to endotoxin, there was an increase in IL-6, TF and CD11b expression and a procoagulant shift of COT. At 4 mmol L-1 nicotinamide, inhibition of TF expression and IL-6 and a normalization of COT were seen. At 16 mmol L-1 nicotinamide, CD11b decreased also. The level of monocyte TF expression correlated with the COT readings, and the endotoxin-induced procoagulant shift of COT could be totally inhibited by blocking TF with an inhibitory antibody. CONCLUSIONS: These results demonstrate the ability of nicotinamide to inhibit the activation of coagulation associated with endotoxemia. We have previously shown that nicotinamide exerts strong anti-inflammatory effects. Evidence is accumulating for nicotinamide to have a therapeutic potential in modulating disease states in which there is a profound activation of coagulation and inflammation, such as in sepsis and disseminated intravascular coagulation.

Nicotinamide is a potent inhibitor of proinflammatory cytokines.

The present study investigates the modulating effects of nicotinamide on the cytokine response to endotoxin. In an in vitro model of endotoxaemia, human whole blood was stimulated for two hours with endotoxin at 1 ng/ml, achieving high levels of the proinflammatory cytokines IL-1 beta, IL-6, IL-8 and TNF alpha. When coincubating whole blood, endotoxin and the vitamin B3 derivative nicotinamide, all four cytokines measured were inhibited in a dose dependent manner. Inhibition was observed already at a nicotinamide concentration of 2 mmol/l. At a concentration of 40 mmol/l, the IL-1 beta, IL-6 and TNF alpha responses were reduced by more than 95% and the IL-8 levels reduced by 85%. Endotoxin stimulation activates poly(ADP-ribose)polymerase (PARP), a nuclear DNA repair enzyme. It has been hypothesized that the anti-inflammatory properties of nicotinamide are due to PARP inhibition. In the present study, the endotoxin induced PARP activation was dose dependently decreased with 4-40 mmol/l nicotinamide or 4-100 micro mol/l 6(5H) phenanthridinone, a specific PARP inhibitor. 6(5H)phenanthridinone however, failed to inhibit the proinflammatory cytokines. Thus, the mechanism behind the cytokine inhibition in our model seems not to be due to PARP inhibition. In conclusion, the present study could not only confirm previous reports of a down-regulatory effect on TNFalpha, but demonstrates that nicotinamide is a potent modulator of several proinflammatory cytokines. These findings demonstrate that nicotinamide has a potent immunomodulatory effect in vitro, and may have great potential for treatment of human inflammatory disease.

Detection of cytochrome P450 mRNA transcripts in prostate samples by RT-PCR.

BACKGROUND: The expression of cytochrome P450 (CYP)-dependent mono-oxygenases in the prostate is important, as it will determine the rate of activation of potential carcinogens as well as the metabolism of hormones with implications in diseases of the prostate. In addition, the levels of cytochromes P450 in prostatic tumours may well be determinants of the outcome of therapy involving P450 substrates such as anti-androgens. METHODS: The gene expression of 12 different CYP genes was measured by reverse transcription-polymerase chain reaction (RT-PCR) in a total of 28 human prostatic tumour and nontumour samples. RESULTS: Intriguingly, a large number of CYP mRNAs were detected in the prostate samples, including CYP1A2, -1B1, -2C19, -2D6, -3A4, -3A5, -3A7 and -4B1. CYP1B1 was consistently expressed and CYP3A5 and CYP4B1 were expressed in a majority of the samples tested. CONCLUSIONS: These data demonstrate a wide range of CYP genes being expressed in the prostate. The relative importance of these enzymes in the pathogenesis and treatment of prostatic disease remains an important theme for further study.

Myocarditis related to clozapine treatment.

Myocarditis has in several case reports been associated with use of clozapine. Eight cases of myocarditis during treatment with clozapine that were submitted to the Swedish Adverse Drug Reaction Advisory Committee and 18 cases that were reported in the literature are summarized. As part of the routine signal detection process on the World Health Organization (WHO) Program on International Drug Monitoring database, which contains more than two million case reports of spontaneously reported suspected adverse drug reactions, a Bayesian confidence propagation neural network (BCPNN) is used. This article also shows the retrospective output of the BCPNN over time for clozapine and myocarditis and discusses its implications. In 19 (79%; duration of treatment not stated for 2 patients) of 24 patients with myocarditis, the symptoms occurred within the first 6 weeks of clozapine treatment. Many patients shared a similar clinical course, with symptoms such as an influenza-like illness, fever, sinus tachycardia, hypotension, chest discomfort, and heart failure. The reaction was fatal in 12 (46%) of these patients. The other patients generally had a prompt recovery. By using the BCPNN technique, a quantitative association between clozapine and myocarditis was demonstrated, and the association might have been high-lighted for clinical review in 1994 had this BCPNN method been in use at the WHO center at the time. Myocarditis seems to be a rare and potentially lethal adverse effect of clozapine. Admittance for observation, interruption of the clozapine treatment, and treatment with corticosteroids should be considered for patients in whom this reaction is suspected.

Active site-inactivated factor VIIa prevents thrombosis without increased surgical bleeding: topical and intravenous administration in a rat model of deep arterial injury.

PURPOSE: The primary event in the procoagulant response after vascular interventions is the tissue factor (TF)-factor VIIa complex formation, which occurs when TF is exposed to the circulating blood by the inflicted trauma. Human recombinant active site-inhibited coagulation factor VIIa (FFR-rFVIIa) binds well to TF but cannot initiate blood coagulation, and should thereby block thrombus formation. This hypothesis was tested with a rat model of arterial thrombosis. METHODS: In a blinded randomized study, the antithrombotic and antihemostatic effects of FFR-rFVIIa and heparin were evaluated in a rat model of mechanical deep arterial injury. In one arm of the study, FFR-rFVIIa (0.2 mg in 150 microL) or vehicle alone was applied topically at the site of vascular injury. In the other arm, FFR-rFVIIa (4 mg/kg), heparin (1 mg/kg), or vehicle alone was injected intravenously. RESULTS: FFR-rFVIIa produced a powerful antithrombotic effect after both topical and intravenous administrations (P =.02 and P =.005, respectively) without increasing the surgical bleeding. Heparin prevented thrombosis equally well as FFR-rFVIIa (P =.0007), but doubled the surgical bleeding compared with FFR-rFVIIa (P =.03) and controls (P =.008). In the topical study, the antithrombotic effect was achieved without altering parameters of plasma anticoagulation (prothrombin time and activated partial thromboplastin time) or producing detectable levels of FFR-rFVIIa in plasma. CONCLUSION: In this model FFR-rFVIIa effectively inhibits thrombus formation without the expense of increased surgical bleeding, which indicates the potential of FFR-rFVIIa as an effective and safe strategy for prevention of thrombosis in reconstructive vascular surgery and various forms of percutaneous revascularization.

Messenger ribonucleic acid levels of steroid 5 alpha-reductase 2 in human prostate predict the enzyme activity.

Testosterone is converted to dihydrotestosterone by 5 alpha-reductase2 in the prostate. Dihydrotestosterone controls cell division, and interindividual differences in prostatic 5 alpha-reductase 2 expression and activity may be a determinant of the risk of developing prostate cancer. However, little is known about interindividual differences in intraprostatic hormonal activity in vivo. To determine whether 5 alpha-reductase-specific messenger RNA (mRNA) is predictive of 5 alpha-reductase activity in prostatic tissue, we analyzed 30 prostatic tissue specimens from 15 Caucasian patients, 47--82 yr old. The mRNA was measured by RT-PCR. Five specimens consisted of cancer, whereas the remaining 25 were derived from benign prostate hyperplasia (BPH). We found a strong association between enzyme activity at pH 5.5 and the 5 alpha-reductase 2-specific mRNA expression when expressed on the basis of beta-actin [Spearman's rank-correlation coefficient (r(s)) = 0.81; 95% confidence interval, 0.64-0.91; P < 0.0001]. The expression of 5 alpha-reductase 2-specific mRNA in the cancer specimens was significantly lower than in the BPH tissue (P = 0.03). There was no difference in the expression of 5 alpha-reductase 1-specific mRNA in the cancer specimens, compared with BPH (P = 0.56). The strong association between 5 alpha-reductase activity at pH 5.5 and the 5 alpha-reductase 2-specific mRNA expression makes it possible to predict prostatic 5 alpha-reductase activity using core needle biopsies.

Monitoring of MRP-like activity in human erythrocytes: inhibitory effect of isoflavones.

A method to fluorometrically monitor efflux of 2',7'-bis-(carboxypropyl)-5(6)-carboxyfluorescein (BCPCF) from human erythrocytes was developed. Genistein, daidzein, sophoraisoflavone A, and licoisoflavone A induced 50% inhibition (IC(50)) of BCPCF efflux at 15-70 microM. The IC(50) value of the most efficient isoflavone, licoisoflavone A (15-25 microM), was comparable to that of indomethacin (approximately 10 microM) and markedly lower than for probenecid (100-200 microM), both known MRP1 inhibitors. Our results indicate that the human erythrocyte is a useful cell model in screening potential MRP inhibitors, that BCPCF is a good substrate for MRP, and that some isoflavones at low concentrations inhibit MRP-mediated efflux.

Antibodies to human herpesvirus 8 latent and lytic antigens in blood donors and potential high-risk groups in Sweden: variable frequencies found in a multicenter serological study.

Human herpesvirus 8 (HHV-8) is a herpesvirus associated with Kaposi's sarcoma (KS). An immunofluorescence assay was used for detection of IgG, IgM, and IgA antibodies against lytic and latent HHV-8 antigens to analyse samples from KS patients (n = 8), healthy blood donors (n = 162), individuals with a high risk sexual behaviour (n = 114), and bone marrow transplant patients (with high risk for bloodborne infections) (n = 34) in Sweden. Of the KS patients, 88% had IgG antibodies to both lytic and latent antigens by immunofluorescence. In all other groups, antilatent antibodies were rare (0-2.6%). IgG antibodies to the lytic antigens were found, by immunofluorescence, in 20% of the blood donors, 31% of the high risk patients, and in 24 and 29% of the bone marrow transplant patients (pre- and post-transplant samples, respectively). For verification of the specificity of the anti-lytic antibodies, 170 of the samples were also tested blindly at different laboratories world-wide with five other assays shown previously to detect HHV-8 antibodies in most KS patients. By using two recombinant HHV-8 proteins (ORF65/vp17 and K8.1/gp 35-37) in ELISA, a whole-virion ELISA and two immunofluorescence assays confirmation of the reactivity against lytic viral antigens was sought. The comparison of the different methods suggested the K8.1 ELISA to be highly specific and also showed a good agreement between two of the immunofluorescence assays. However, generally there was a poor correlation for positive results, indicating the need of further methodological development.

MAPK/ERK signaling in activated T cells inhibits CD95/Fas-mediated apoptosis downstream of DISC assembly.

When T cells are activated, the expression of the CD95 ligand is elevated, with the purpose of inducing apoptosis in target cells and to later eliminate the activated T cells. We have shown previously that mitogen-activated protein kinase (MAPK or ERK) signaling suppresses CD95-mediated apoptosis in different cellular systems. In this study we examined whether MAPK signaling controls the persistence and CD95-mediated termination of an immune response in activated T cells. Our results show that activation of Jurkat T cells through the T cell receptor immediately suppresses CD95-mediated apoptosis, and that this suppression is mediated by MAPK activation. During the phase of elevated MAPK activity, the activation of caspase-8 and Bid is inhibited, whereas the assembly of a functional death-inducing signaling complex (DISC) is not affected. These results explain the resistance to CD95 responses observed during the early phase of T cell activation and suggest that MAPK-activation deflects DISC signaling from activating caspase-8 and Bid. The physiological relevance of the results was confirmed in activated primary peripheral T cells, in which inhibition of MAPK signaling markedly sensitized the cells to CD95-mediated apoptosis.

Effect of locally-applied active site-blocked activated factor VII (ASIS) on experimental arterial thrombosis.

The starting point of blood coagulation in vivo is the formation of a complex between tissue factor (TF), which is exposed following vascular disease or trauma, and activated blood coagulation factor VII (FVIIa). This blinded, random, paired study evaluates whether active site-blocked activated FVII (FVIIai, ASIS), which binds avidly to TF but is unable to initiate the coagulation processes, inhibits experimental thrombosis. Arteriotomy and deep vessel wall trauma were performed in the central arteries of rabbits' ears. The topical administration of ASIS (0.5 mg in 200 microl vehicle) resulted in a distinct antithrombotic effect compared to vehicle alone. Patency rates at 30 and 120 min after reperfusion were 85% and 75% in the ASIS group and 45% and 30% in the vehicle group, respectively (P = 0.008 and P = 0.004). In contrast, intravenous administration of ASIS (4 mg/kg) produced no antithrombotic effect. Arteriotomy bleeding times were 1.5 min in the ASIS group and 2.0 min in the vehicle group (medians, P = 1). Local application of ASIS produces a pronounced antithrombotic effect in rabbits without giving rise to antihaemostatic side-effects. This mode of treatment may have a potential for a variety of clinical interventions in injured or diseased vessels.

Association of venous thromboembolism and clozapine.

Data from the Swedish Adverse Reactions Advisory Committee suggest that use of clozapine is associated with venous thromboembolic complications. We summarise 12 cases of thromboembolism during clozapine treatment. In five cases the outcome was fatal.

Gemini (dimeric) surfactant perturbation of the human erythrocyte.

We studied the ability of di-cationic gemini surfactantsdi (amphiphiles), i.e. 1,4-butanediammonium-N,N-dialkyl-N,N,N',N'-tetramethyl bromides (Di-Cm-di-QAS (s = 4), where m = 8, 11, 13, 16 and s = the number of alkyl groups in the spacer) to induce shape alteration, vesiculation, haemolysis and phosphatidylserine exposure in human erythrocytes, and to protect erythrocytes against hypotonic haemolysis. At high sublytic concentrations the Di-Cm-di-QAS (s = 4) amphiphiles rapidly induced echinocytic (spiculated) shapes and a release of exovesicles, mainly in the form of tubes, from the cell surface. Following 60 min incubation erythrocytes were sphero-echinocytic and a few cells with invaginations/endovesicles were observed. No phosphatidylserine exposure was detected. The haemolytic potency increased with an increase of the alkyl chain length. At sublytic concentrations the Di-Cm-di-QAS (s = 4) amphiphiles protected erythrocytes against hypotonic haemolysis. It is suggested that the Di-Cm-di-QAS (s = 4) amphiphiles perturb the membrane in a similar way as single-chain cationic amphiphiles, but that they do not easily translocate to the inner membrane leaflet.

Processing of laser-Doppler signals from free flaps.

As conventional graphical laser-Doppler flowmetric (LDF) registrations from free flaps are difficult to interpret we explored the use of refined computerized signal processing to enhance the reliability of the blood flow supervision postoperatively. From eleven free flaps LDF data were collected using a software programme and a personal computer for analysis. Findings were compared with the clinical outcome. Nine flaps healed whereas one had wound problems and one suffered a partial necrosis. From the nine uneventful flaps, a peak within the range of frequencies from 0.04 to 0.23 Hz was seen. In the remaining two, such a low frequency peak could hardly be observed. Frequency analysis using computerized processing of LDF signals thus has the capacity to demonstrate the status of the flap perfusion. The slow wave vasomotion component seems to be of particular importance. Other frequency components warrant further investigation. A custom made monitoring device would be of great clinical value.

PBSC harvests individually optimized by using pre-collection CD34(+) values and on-line flow cytometric analysis of the mononuclear cell enrichment.

BACKGROUND: We have investigated how the amount of blood processed during collection of PBSC affects the yield of CD34 cells. METHODS: We first established a method of significantly increasing the enrichment of mononuclear cells (MNC), CD34(+) cells and granulocyte-macrophage progenitors (GM-CFU) by on-line flow cytometric (FCM) analysis of the leukocyte populations in the collect line. A total of 166 PBSC collections from 94 patients, were devided into five groups according to the blood volume processed: < 12 L of processed blood, 12-13L, 13-14L, 14-15L and > 15L. RESULTS: When the yield of CD34(+) cells war compared between these groups, a positive correlation was seen (r=0.97) between the processed blood volume and the yield, expressed as a ratio between total number of CD34(+) cells in the harvest and the CD34(+) cell concentration in blood. This correlation can be used to estimate the volume that must be processed to exceed a specific target number of CD34(+) cells. The implications of these results on the need for one, two or more leukapheresis procedures in order to collect a sufficient amount of stem and progenitor cells for a given patient are discussed, i n relation to clinical logistics and the benefits for the patients. DISCUSSION: PBSC harvest can be improved by individually-adjusted leukapheresis according to on-line FCM analysis and pre-harvest levels of CD34(+) cells and the processed blood volume can be used to predict the CD34(+) yield.

Kinetics of bradykinin levels during and after leucocyte filtration of platelet concentrates.

OBJECTIVE: To measure bradykinin levels in platelet concentrates during and after leucocyte filtration. METHODS: Platelet concentrates were leukocyte depleted using three different leucocyte-depletion filters selected to represent filters with negative, positive or neutral charge, respectively. Bradykinin levels were analysed before, during and up to 90 min post-filtration. RESULTS: Significant levels of bradykinin were generated when negatively charged leucocyte depletion filters were used. However, we found a high variation between platelet concentrates prepared from different donors as well as within the same concentrate when this was divided into three aliquots. Generated bradykinin was rapidly degraded in the collection bag and no bradykinin was detectable 60 min post-filtration. CONCLUSION: Bradykinin generation is more pronounced when negatively charged leucocyte removal filters are used. Due to a rapid degradation of bradykinin in the storage bag, pre-storage filtration should minimise the risk of bradykinin related adverse reactions during transfusion with some filters.

No correlation between activated protein C resistance and free flap failures in 100 consecutive patients.

This study evaluates whether thrombophilic disorders contribute to failures in microvascular surgery. A recently discovered condition is focused on, i.e., activated protein C resistance, which is a highly prevalent functional defect of a crucial endogenous anticoagulant system--the protein C anticoagulant pathway (up to 15 percent of Caucasians affected). One hundred consecutive patients were operated on with 103 free tissue transfers during a 2.5-year period, all of which received perioperative intravenous anticoagulation, principally based on dextran (1 liter) and a heparin bolus at vascular reperfusion (80 to 100 IU/kg). The patients underwent extensive laboratory analysis with respect to conditions predisposing for thrombosis. Eleven patients were found to be activated protein C resistant, and one patient had congenital protein S deficiency. There were six total and five partial flap losses, which, however, in only one case coincided with the presence of a thrombophilic disorder (activated protein C resistance). By contrast, a substantial portion of flap necroses could be related to nonconstitutional factors (for example, pedicle kinking). It is concluded that routine screening for hypercoagulable states such as activated protein C resistance is not necessary in microvascular surgery.

Finger skin blood flow in response to indirect cooling in normal subjects and in patients before and after sympathectomy.

Finger skin blood flow was measured in 80 healthy subjects, using laser Doppler imaging during basal vasodilatation at a local temperature of 40 degrees C. The response to cooling of the contralateral hand at 15 degrees C was studied. A vasoconstriction index was calculated in all subjects and a nomogram was constructed, taking age into consideration. Compared with these normal subjects, four patients operated on with transthoracic endoscopic sympathectomy due to hand hyperhidrosis showed clearly attenuated responses. The results indicate that the test can be used to assess disturbances in the sympathetic regulation of the peripheral blood flow.