Distribution, Identification, and Quantification of Residues after Treatment of Ready-To-Eat Salami with 36Cl-Labeled or Nonlabeled Chlorine Dioxide Gas.

When ready-to-eat salami was treated in a closed system with 36Cl-labeled ClO2 (5.5 mg/100 g of salami), essentially all radioactivity was deposited onto the salami. Administered 36ClO2 was converted to 36Cl-chloride ion (>97%), trace levels of chlorate (<2%), and detectable levels of chlorite. In residue studies conducted with nonlabeled ClO2, sodium perchlorate residues (LOQ, 4 ng/g) were not formed when reactions were protected from light. Sodium chlorate residues were present in control (39.2 ± 4.8 ng/g) and chlorine dioxide treated (128 ± 31.2 ng/g) salami. If sanitation occurred under conditions of illumination, detectable levels (3.7 ± 1.5 ng/g) of perchlorate were formed along with greater quantities of sodium chlorate (183.6 ± 75.4 ng/g). Collectively, these data suggest that ClO2 is chemically reduced by salami and that slow-release formulations might be appropriate for applications involving the sanitation of ready-to-eat meat products.

Distribution and chemical fate of ³6Cl-chlorine dioxide gas during the fumigation of tomatoes and cantaloupe.

The distribution and chemical fate of (36)Cl-ClO2 gas subsequent to fumigation of tomatoes or cantaloupe was investigated as were major factors that affect the formation of chloroxyanion byproducts. Approximately 22% of the generated (36)Cl-ClO2 was present on fumigated tomatoes after a 2 h exposure to approximately 5 mg of (36)Cl-ClO2. A water rinse removed 14% of the radiochlorine while tomato homogenate contained ∼63% of the tomato radioactivity; 24% of the radiochlorine was present in the tomato stem scar area. Radioactivity in tomato homogenate consisted of (36)Cl-chloride (≥80%), (36)Cl-chlorate (5 to 19%), and perchlorate (0.5 to 1.4%). In cantaloupe, 55% of the generated (36)Cl-ClO2 was present on melons fumigated with 100 mg of (36)Cl-ClO2 for a 2 h period. Edible cantaloupe flesh contained no detectable radioactive residue (LOQ = 0.3 to 0.4 µg/g); >99.9% of radioactivity associated with cantaloupe was on the inedible rind, with <0.1% associated with the seed bed. Rind radioactivity was present as (36)Cl-chloride (∼86%), chlorate (∼13%), and perchlorate (∼0.6%). Absent from tomatoes and cantaloupe were (36)Cl-chlorite residues. Follow-up studies have shown that chlorate and perchlorate formation can be completely eliminated by protecting fumigation chambers from light sources.

Ecotoxicology of synthetic pyrethroids.

In this chapter we review the ecotoxicology of the synthetic pyrethroids (SPs). SPs are potent, broad-spectrum insecticides. Their effects on a wide range of nontarget species have been broadly studied, and there is an extensive database available to evaluate their effects. SPs are highly toxic to fish and aquatic invertebrates in the laboratory, but effects in the field are mitigated by rapid dissipation and degradation. Due to their highly lipophilic nature, SPs partition extensively into sediments. Recent studies have shown that toxicity in sediment can be predicted on the basis of equilibrium partitioning, and whilst other factors can influence this, organic carbon content is a key determining variable. At present for SPs, there is no clear evidence for adverse population-relevant effects with an underlying endocrine mode of action. SPs have been studied intensively in aquatic field studies, and their effects under field conditions are mitigated from those measured in the laboratory by their rapid dissipation and degradation. Studies with a range of test systems have shown consistent aquatic field endpoints across a variety of geographies and trophic states. SPs are also highly toxic to bees and other nontarget arthropods in the laboratory. These effects are mitigated in the field through repellency and dissipation of residues, and recovery from any adverse effects tends to be rapid.

Optical properties and plasmon resonances of titanium nitride nanostructures.

We examine the optical properties of nanostructures comprised of titanium nitride, TiN, an electrically conducting intermetallic-like compound. This material can be deposited in the form of durable films by physical vapor deposition. Use of nanosphere templating techniques extends the range of nanostructures that can be produced to include the versatile semi-shell motif. The dielectric properties of TiN(1-x) depend upon stoichiometry and are favorable for plasmon resonance phenomena in the mid-visible to near-infrared range of the spectrum and for x approximately 0. We analyze the optical phenomena operating in such structures using a combination of experiment and simulation and show that semi-shells of TiN exhibit a tunable localized plasmon resonance with light. The material is, however, unsuitable for applications in which a long-distance surface plasmon polariton is desired.

The effect of the long term aspirin administration on the progress of atherosclerosis in apoE-/- LDLR-/- double knockout mouse.

UNLABELLED: We have investigated the effects of differential aspirin doses on atherogenesis. Aspirin was given to homozygous, apoE(-/-) and LDLR(-/-) double deficient mice for 12 weeks. The development of arteriosclerosis was determined morphologically by image analysis and endothelial cell function was assessed by measurement of peripheral nitric oxide (NO). METHODS: ApoE(-/-) LDLR(-/-)double knockout mice were bred and maintained with a high fat diet containing aspirin (4 and 40 mg/kg B.W. /day) for twelve weeks. The development of arteriosclerosis was monitored by estimating the total area of atherosclerotic lesions in the entire aorta. Acetylcholine-induced NO release was measured in vivo using electrochemical sensors. The expression of eNOS on the endothelial surface was determined by immuno-staining. Plasma prostaglandin F1alpha (PGF(1 alpha)), serum thromboxian B(2) (TXB(2)) and total cholesterol were measured using enzymatic assay. Bleeding time was measured by tail cut method. RESULTS: Arteriosclerosis in the 4 mg/kg/day aspirin group was decreased significantly compared with the placebo group, but not in the 40 mg/kg/day aspirin group. Acetylcholine-induced NO release was significantly depressed in the 40 mg/kg/day aspirin group. Immunochemical analysis with anti-eNOS antibody supported these findings. In the 4 mg/kg/day aspirin group, the severe suppression of PGI(2) production was not confirmed in spite of decreasing TXB(2) production, but not in the 40 mg/kg/day aspirin group. CONCLUSION: Our results suggest that endothelial dysfunction with low dose aspirin improved, reduced progression of atherosclerosis in apoE(-/-) and LDLR(-/-) double deficient mice and provides a pathophysiological basis for the beneficial effects of aspirin in atherosclerosis, and low doses appeared to be more efficient than high doses.

Animal models of cough: literature review and presentation of a novel cigarette smoke-enhanced cough model in the guinea-pig.

A wealth of literature describes the approaches that investigators have used to develop animal models of cough. The relevance of the models to cough in man and disease is still unknown. Furthermore, the choice of animal model that is used will depend on the purpose of the investigation and what questions are being asked. Cigarette smoke is known to cause COPD and cough is a principle symptom where patients demonstrate an increased cough response to citric acid or capsaicin. This paper describes the development of exacerbated cough to these agents in the guinea-pig following cigarette smoke exposure and pharmacological profiling of these models. Male Dunkin-Hartley guinea-pigs were exposed to air or cigarette smoke (4 or 5 research cigarettes daily for the capsaicin and citric acid studies, respectively) for a 3 s puff every 30 s, for up to 10 days. At selected time points conscious, unrestrained animals were placed in a plethysmograph chamber and challenged with an aerosol of 0.3 M citric acid (10 min) or 10 microM capsaicin (7 min). Cough and Penh area under the curve (AUC) were recorded during the exposure and for a further 10 min (citric acid) or 8 min (capsaicin) after exposure. Compounds were administered on day 3 or 11 for citric acid or capsaicin, respectively. Significant enhancement of citric acid-induced cough was evident 24 h (12+/-2 to 24+/-4* coughs) after a single exposure and further enhanced after 2 days (13+/-3 to 36+/-4* coughs). Enhanced cough to capsaicin was not reliable until after 10 days of cigarette smoke exposure (2+/-1 to 14+/-3** coughs). Data are expressed as mean+/-s.e.mean (n=10), *p<0.05, **p<0.01 vs. air-exposed animals (Mann-Whitney rank-sum test). The minimum effective doses to inhibit citric acid-induced cough were 10, 10, 3 and 0.3 mg/kg for codeine (p.o. -30 min), a selective NK(1)/NK(2) antagonist, DNK333 (p.o. -2 h), terbutaline (s.c. -1 h) and atropine (s.c. -1 h), respectively. The minimum effective doses to inhibit capsaicin-induced cough were 3, 1, 0.3 and 0.3 mg/kg for codeine, DNK333, terbutaline (p.o. -2 h) and atropine, respectively. The VR1 antagonists capsazepine and iodo-resiniferatoxin (IRTX) did not inhibit cough in either model. Differences in sensitivity between citric acid and capsaicin to pharmacological agents may be partly explained by the difference in magnitude of response to these agents. Clinically used compounds such as codeine and terbutaline have shown activity in both models, however the relevance of the models to cough in man and disease for potential new therapies is unknown.

The free-radical scavenger, edaravone, augments NO release from vascular cells and platelets after laser-induced, acute endothelial injury in vivo.

In vitro and in vivo experimental models have demonstrated that vascular endothelial function is significantly impaired as a result of oxidative stress, mediated by the generation of oxygen-derived free radicals in response to chronic or acute inflammation. In particular, super-oxide () at specific concentrations leads to the impairment of nitric oxide (NO) bioactivity, and it is known that NO plays a fundamental role in the maintenance of vascular homeostasis. The relationship between reactive oxygen species (ROS) and NO release in thrombosis-related endothelial damage in the peripheral microvasculature remains unclear, however. The purpose of the present study was to investigate the effect of the free-radical scavenger, edaravone, on NO synthesis and thrombotic potential in arterioles after exposure to laser irradiation. Highly sensitive electrochemical NO microsensors were positioned in femoral arterioles of mice, and the kinetics of NO release were recorded in response to standardized laser irradiation in vivo. In addition, images of NO release from damaged vascular cells were investigated in a similar rat model using the NO-sensitive dye 4,5-diaminofluorescein diacetate (DAF-2DA). Thrombogenesis was assessed in carotid arterioles by continuous video microscopy using image analysis software. Laser irradiation led to NO release from perturbed endothelial cells and from platelet-rich thrombi. Edaravone had no significant effect on NO release in non-laser treated, intact endothelium compared with placebo. In contrast, edaravone demonstrated a dose-dependent effect on NO release and thrombogenicity. At a concentration of 10.5 mg/kg per h, edaravone promoted a 5-fold increase in NO and a reduction in platelet-rich thrombus volume to 58% of the placebo values. Our data provide direct evidence to confirm that acute endothelial damage in peripheral microvessels initially induces NO release and that the free-radical scavenger, edaravone, augments NO synthesis leading to suppression of platelet thrombus formation.

Varying the ratio of dietary n-6/n-3 polyunsaturated fatty acid alters the tendency to thrombosis and progress of atherosclerosis in apoE-/- LDLR-/- double knockout mouse.

We have investigated the influence of dietary n-6/n-3 (ù-6/ù-3) polyunsaturated fatty acid-balance on the tendency to arterial thrombosis and the progress of atherosclerosis in apoE-/- LDLR-/- double knockout mouse. Homozygous apoE-/- LDLR-/- double knockout mouse (DKO mice, 129XC57BL/6J background) and male C57BL/6 mice aged 6 weeks were divided into four groups. Each group was fed a diet containing a different n-6/n-3 ratio (Group l: 0.29; Group 2: 1.43; Group 3: 5.00; Group 4: 8), prepared with high linolenic (LNA) flaxseed oil (n-3 rich) and high linoleic (LA) safflower oil (n-6 rich). There were no statistical differences in the gain in body weight between the four groups. After 16 weeks, plasma triglyceride and LDL levels in Group 1 were significantly lower than in the other groups. Conversely, HDL was the highest. After 8 and 16 weeks, the tendency to arterial thrombosis was assessed using a He-Ne laser-induced thrombosis model. The degree of atherosclerosis was measured using the entire aorta method employing image analysis software. The n-6/n-3 ratio had a dose-dependent antithrombotic effect (thrombus volume decreased 23%, Group 1 vs. Group 4), In addition, the extent of atherosclerosis was less in the animals fed a low n-6/n-3 ratio compared with the high n-6/n-3 ratio group (atherosclerotic area decreased 40%, Group 1 vs. Group 4). The lowest n-6/n-3 ratio tested (0.29) was the most effective in suppressing the thrombotic and atherosclerotic parameters in these DKO mice.

Soluble adhesion molecules in inflammatory and vascular diseases.

For many years the vascular endothelium was believed simply to provide a passive lining between circulating blood and extravascular tissue. It is now clear, however, that this monolayer of cells on the luminal surface of all blood vessels, provides a selective barrier that responds dynamically to various stimuli, and controls a complex series of cellular reactions and interactions. The current presentation describes the use of computer enhanced video recording to study interactions between endothelial cells and circulating blood cells, especially leucocytes. Subsequently, modern assays for soluble cell adhesion molecules and other cell receptors were assessed for potential use in routine clinical practice. The results demonstrated that adhesive mechanisms involving leucocytes and endothelial cells involve a range of interrelationships that cut across conventional views of haemostasis and leucocyte function. The findings also suggest that interplay between the vascular lumen and circulating blood cells might be vitally important in clinically demanding pathologies, such as life-threatening sepsis, ischaemic heart disease, atherosclerosis and cancer. The concepts provide challenging strategies for further investigation.

Systemic haemostasis after intermittent pneumatic compression. Clues for the investigation of DVT prophylaxis and travellers thrombosis.

Intermittent pneumatic compression (IPC) is known to provide effective prophylaxis against post-surgical deep-vein thrombosis (DVT), and other procedures based on reducing venous stasis have been promoted recently to minimize the risk of thromboembolism after long-haul travel ('travellers thrombosis'). This study sought to measure the effects of IPC on systemic haemostasis, which are currently disputed. IPC was applied for 120 min on 21 male, non-smoking volunteers ranging in age from 19 to 47 years. IPC promoted a significant increase in global fibrinolytic potential. Levels of urokinase plasminogen activator activity (uPA) measured using an amidolytic assay were raised after IPC. However, enzyme-linked immunosorbent assays (ELISA) of uPA antigen, and the activities of tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1) were not statistically different from those in control experiments. IPC led to highly significant falls in factor VIIa, associated with increased levels of tissue factor pathway inhibitor (TFPI). IPC enhances fibrinolysis and suppresses procoagulant activation. Measurements of specific fibrinolytic components do not reflect overall fibrinolytic activity and are highly dependent on the method of assay. The results provide important clues for detailed studies of the effects of haemodynamics on systemic haemostasis.

Unresponsiveness to factor VIII inhibitor bypassing agents during haemostatic treatment for life-threatening massive bleeding in a patient with haemophilia A and a high responding inhibitor.

We report a case of haemophilia A with a high responding inhibitor of factor VIII (FVIII) who had a serious retroperitoneal haematoma caused by penetration of a duodenal ulcer. Inhibitor-bypassing therapy was commenced immediately on admission. On the 17th day of treatment with activated prothrombin complex concentrate (APCC; FEIBA, re-bleeding occurred and thrombelastography (TEG) demonstrated resistance to therapy. Treatment was changed to recombinant activated factor VII (rFVIIa; NovoSeven and resulted in clinical improvement together with an improvement in TEG parameters. On the 10th day of continuous infusion with NovoSeven, however, TEG again showed resistance to therapy. FEIBA infusions were re-introduced and TEG results remained satisfactory for 7 days. On day 34, however, further retroperitoneal bleeding was evident and a decline in the haemostatic efficiency of FEIBA was recorded by TEG. NovoSeven was again successfully administered for 7 days. There were no laboratory findings to indicate disseminated intravascular coagulation (DIC), hypercoagulability or abnormal fibrinolysis. The plasma-based clotting tests did not show any additional prolongation on the occasions when the TEG demonstrated unresponsiveness to FEIBA or NovoSeven. These findings suggested that some component of whole blood, other than plasma might have governed the TEG data. The long-term use of APCC such as FEIBA or rFVIIa, requires careful monitoring in terms of FVIII inhibitor bypassing activity as well as the tendency to DIC.

Magnitude and direction of thermal diffusion of colloidal particles measured by thermal field-flow fractionation.

In this paper we provide experimental evidence showing that various types of submicrometer-sized particles (latexes, inorganic, and metallic), suspended in either aqueous or nonaqueous carrier liquids to which a temperature gradient dT/dx is applied, experience a force in the direction opposite to that of dT/dx. This behavior is similar to that of small particles such as soot, aerosols, and small bubbles suspended in stagnant gases across which temperature gradients are applied, a phenomenon known as "thermophoresis in gases." We report the use of a thermal field-flow fractionation (ThFFF) apparatus in two different configurations to establish the direction of particle motion subject to a temperature gradient. The first approach employed the conventional horizontal ThFFF channel orientation. In this case, small electrical potentials were applied across the narrow channel thickness either to augment or to act in opposition to the applied thermal gradient, depending on whether the accumulation wall was maintained at a positive or negative potential relative to the depletion wall. Thus, by observing the changes in the retention behavior of surface-charged latices or silica particles with changes in potential difference across the channel thickness, we were able to ascertain the direction of migration of the particles in the thermal gradient. The second approach involved the use of a ThFFF column oriented vertically in an implementation of a technique known as thermogravitational FFF. In this approach, the convective flow along the channel length (due to density gradients associated with the temperature gradient) couples with the thermal diffusion effect across the channel thickness to result in a combined particle retention mechanism. A retarded upward migration rate is indicative of accumulation of particles at the cold wall, while enhanced upward migration would indicate a hot-wall accumulation. From the results of our investigations, we conclude that submicrometer-sized particles suspended in either aqueous or nonaqueous carrier liquids and subjected to a temperature gradient migrate from the hot wall toward the cold wall of a ThFFF channel.

Incidence of embolism and paravalvar leak after St Jude Silzone valve implantation: experience from the Cardiff Embolic Risk Factor Study.

BACKGROUND: Silver coating of the sewing ring (Silzone) was introduced as a modification of the St Jude Medical standard valve to provide antibacterial protection, but the valve has recently been withdrawn. OBJECTIVE: To study patients with these prostheses to assess possible adverse effects, and to guide their follow up. DESIGN: Prospective observational study of risk factors for stroke after valve replacement. SETTING: Cardiology and cardiac surgery departments in a tertiary centre. PATIENTS: There were 51 patients with Silzone and 116 with St Jude Medical standard valves. Patients undergoing aortic valve replacement were well matched for stroke risk factors. Silzone patients with mitral valve replacement were younger (mean (SD) age 61 (10) v 66 (7) years), more likely to be female (95% v 65%), and had more pulmonary arterial hypertension (100% v 78%), but fewer coronary artery bypass grafts (5% v 33%) than patients with standard mitral valve replacements (all p < 0.05). RESULTS: Follow up was 100% in the Silzone group (mean duration 3.0 (0.9) years) and 97.4% in the standard group (4.7 (1.4) years). Survival, morbidity, and anticoagulant control were documented over 682 follow up years (153 for Silzone and 529 for standard). There were six embolic strokes and one peripheral embolism in the Silzone group, all within three months after operation, and five embolic strokes and one peripheral embolism in the standard group. Freedom from major thromboembolism at three months was 65% in the Silzone mitral valve replacement group and 100% in the standard mitral valve replacement group (difference 35%, 95% confidence interval 8% to 62%). There was one reoperation for paravalvar leak in the standard group, but none in the Silzone group (NS). Anticoagulant control in the two groups was similar. CONCLUSIONS: Patients with Silzone mitral valves had a high rate of early postoperative embolism but no excess paravalvar leak.

Management of haemophilia B inhibitor patients with anaphylactic reactions to FIX concentrates.

Allergic reactions to concentrates containing factor IX (FIX) are serious complications in the treatment of haemophilia B patients with inhibitor. We have established a therapeutic protocol for such cases using an initial skin test followed by step-wise infusions of FIX concentrates under hydrocortisone cover. We have successfully treated three patients whose treatment with FIX had been suspended.

The effect of dietary bacillus natto productive protein on in vivo endogenous thrombolysis.

The influence of dietary bacillus natto productive protein (BNPP) on endogenous thrombolysis was investigated in the rat. Animals were given a standard feed for 14 weeks, to which 0.2 or 1% BNPP was added. Thrombolysis was evaluated using an He-Ne laser-induced thrombosis model in mesenteric microvessels. Changes in thrombus volume, reflecting thrombolysis, decreased to 82% of the initial value in the control group. In contrast, the thrombus volume decreased to 67% in the animals fed 0.2% BNPP, and decreased to 51% in the group given 1% BNPP. The extent of thrombolysis in the 1% BNPP group was equivalent to that seen in animals treated with a bolus intravenous infusion of 0.2 mg/kg tissue plasminogen activator. The results demonstrated that the dietary administration of BNPP enhanced endogenous thrombolysis in a dose-dependent manner. Argatroban (2 mg/kg/h) enhanced endogenous fibrinolysis only in control animals, but not in the BNPP groups. The results support the suggestion that dietary supplementation with BNPP may provide a simple means to promote fibrinolysis not only in the treatment of thromboembolism but also in the prevention of venous occlusion.

Cerebral thrombosis and microcirculation of the rat during the oestrous cycle and after ovariectomy.

1. The effects of oestrogen on thrombogenesis and the cerebral microcirculation of the female rat were studied during the oestrous cycle and after ovariectomy. 2. Serum levels of oestradiol (E2) and plasma concentrations of nitric oxide (NO) metabolites were significantly greater at pro-oestrus than at dioestrus. Blood vessel diameter, mean red cell velocity, wall shear rate and blood flow at pro-oestrus were significantly higher than at dioestrus. Thrombotic tendency, assessed using a He-Ne laser-induced thrombosis model, was significantly decreased at pro-oestrus compared with dioestrus. 3. The long-term deprivation of oestrogen by ovariectomy significantly depressed serum levels of E2 and plasma concentrations of NO metabolites. Thrombotic tendency was significantly increased 4 weeks after ovariectomy. Vessel diameter, mean red cell velocity, wall shear rate and blood flow in pial arterioles were significantly reduced after ovariectomy. 4. Exogenous administration of oestrogen (17 beta-oestradiol) after surgery reversed the increased thrombotic tendency mediated by ovariectomy. 5. These results strongly indicate that oestrogen mediates beneficial effects on the cerebral microcirculation and moderates cerebral thrombotic mechanisms in the female rat.

Enhanced thrombolysis induced by argatroban or activated protein C in the presence or absence of staphylokinase, measured in an in vivo animal model using mesenteric arterioles.

Successful administration of thrombolytic agents is associated with vessel reocclusion in a high proportion of cases. We have previously established an animal model to investigate platelet-rich thrombolytic mechanisms in vivo and demonstrated that recombinant staphylokinase (rSAK)-induced thrombolysis was enhanced by the concomitant administration of the direct thrombin inhibitor argatroban. The present study expanded the use of this model by comparing arterial and venous thrombolysis using advanced image analysis software. Mural thrombi were formed by Helium-Neon laser irradiation in mesenteric arterioles and were shown to be lysed, dose-dependently, by smaller amounts of rSAK than those required in venules. Activated protein C (APC), as well as argatroban, enhanced the rSAK-induced thrombolysis. APC or argatroban also induced thrombolysis in the absence of rSAK, and the effect was inhibited by tranexamic acid. The enhanced thrombolysis induced by APC or argatroban in the presence or absence of rSAK may be due to increased endogenous thrombolysis mediated by the inhibition of thrombin activity or delayed thrombin generation.

Successful arthroscopic treatment of pigmented villonodular synovitis of the knee in a patient with congenital deficiency of plasminogen activator inhibitor-1 and recurrent haemarthrosis.

We report the arthroscopic treatment of pigmented villonodular synovitis (PVNS) in a 13-year-old Japanese boy with congenital partial deficiency of plasminogen activator inhibitor-1 (PAI-1). He was admitted to our hospital with recurrent haemarthrosis of his right knee. Characteristic abnormalities of fibrinolysis included shortened euglobulin lysis time, low PAI-1 activity and low PAI-1 antigen levels. In addition, levels of "active PAI" in the plasma, which is a measure of total PAI bound to exogenous plasminogen activator, were very low. These parameters remained low after venous occlusion. The diagnosis of PVNS was established by synovial membrane biopsy, and arthroscopic synovectomy was performed with adjuvant administration of intravenous tranexamic acid. Subsequent bleeding episodes have been well controlled by oral administration of tranexamic acid on demand.