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Safety and efficacy of pasteurized C1 inhibitor concentrate (Berinert P) in hereditary angioedema: a review. jean.de.serres@aventis.com.

BACKGROUND: Hereditary angioedema caused by C1 inhibitor deficiency can be life threatening. Acute exacerbations are treated with intravenous purified, pasteurized C1 esterase inhibitor concentrate at doses of 500-1000 IU. METHODS: We reviewed the literature about safety and efficacy of the C1 inhibitor concentrate used in Canada (Berinert P) or relevant to it. RESULTS: Post-marketing experience since 1985 is reassuring. There were few adverse events and no transmission of infection with the pasteurized product. A number of case reports, retrospective studies and few randomized or non-randomized prospective studies have shown good efficacy measured as clinical resolution of symptoms or in time to resolution, time to relief or time to improvement. CONCLUSIONS: There are numerous observational studies showing good efficacy and safety and a long post-marketing experience although few randomized placebo-controlled trials.

Angioedema↗

Contamination flows of Bacillus cereus and spore-forming aerobic bacteria in a cooked, pasteurized and chilled zucchini purée processing line.

A food processing plant producing pasteurized purées and its zucchini purée processing line were examined for contamination with aerobic and facultative anaerobic bacterial spores during a day's operation. Multiplication of spores was also monitored in the product stored under different conditions. High concentrations of Bacillus cereus spores were found in the soil in which the zucchinis were grown (4.6+/-0.3 log CFU/g), with a background spore population of 6.1+/-0.2 log CFU/g. In the processing plant, no B. cereus or psychrotrophic bacterial spores were detected on equipment. B. cereus and psychrotrophic bacterial spores were detected after enrichment in all samples of raw zucchinis, washed zucchinis, of two ingredients (starch and milk proteins) and in processed purée at each processing step. Steam cooking of raw zucchinis and pasteurization of purée in the final package significantly reduced spore numbers to 0.5+/-0.3 log CFU/g in the processed food. During storage, numbers of spore-forming bacteria increased up to 7.8+/-0.1 log CFU/g in purée after 5 days at 20-25 degrees C, 7.5+/-0.3 log CFU/g after 21 days at 10 degrees C and 3.8+/-1.1 log CFU/g after 21 days at 4 degrees C. B. cereus counts reached 6.4+/-0.5 log CFU/g at 20-25 degrees C, 4.6+/-1.9 log CFU/g at 10 degrees C, and remained below the detection threshold (1.7 log CFU/g) at 4 degrees C. Our findings indicate that raw vegetables and texturing agents such as milk proteins and starch, in spite of their low levels of contamination with bacterial spores and the heat treatments they undergo, may significantly contribute to the final contamination of cooked chilled foods. This contamination resulted in growth of B. cereus and psychrotrophic bacterial spores during storage of vegetable purée. Ways to eliminate such contamination in the processing line are discussed.

Bacillus cereus↗

Use of redox potential modification by gas improves microbial quality, color retention, and ascorbic acid stability of pasteurized orange juice.

The aim of this paper was to study the effect of both redox potential (Eh) and pasteurization of orange juice on stability of color and ascorbic acid, and growth recovery of microorganisms during storage at 15 degrees C for 7 weeks. Three conditions of Eh, +360 mV (ungassed), +240 mV (gassed with N2), and -180 mV (gassed with N2-H2) were applied to orange juice. Both thermal destruction and recovery of sublethally heat-injured cells of Lactobacillus plantarum and Saccharomyces cerevisiae were investigated. While oxidizing conditions were the most effective for thermal destruction of L. plantarum and S. cerevisiae, reducing conditions decreased recovery of heated cells of S. cerevisiae. In addition, gassing the juice with N2 or N2-H2 increased color retention and ascorbic acid stability. The present study demonstrated that juice must be reduced just after the heat treatment in order, firstly, to maximize microbial destruction during pasteurization, and secondly, to prevent the development of microorganisms and stabilize color and ascorbic acid during storage.

Ascorbic Acid↗

Development of a quantitative risk assessment model for Salmonella enteritidis in pasteurized liquid eggs.

The performance of hazard analyses and the establishment of critical limits by the food industry are both hampered by the inability to directly relate food processing operations from farm-to-table with their public health impact. Using a 'unit operations' and stochastic simulation approach, data on the frequency of pathogens in raw ingredients, predictive microbiology models for growth and inactivation (thermal and non-thermal), and dose-response models for infectivity were integrated to create a quantitative risk assessment model for a Salmonella enteritidis infection from thermally processed liquid whole eggs made into mayonnaise in the home. The risk assessment indicated pasteurization provides sufficient consumer protection from a high incidence of infected birds and from temperature abuse between the farm and the egg breakers. However scenarios showed how inadequate pasteurization temperatures and/or temperature abuse during storage leads to a hazardous product. This dynamic approach to modeling risk should aid in identification and setting critical control points and assessing the impact of altering food formulations or processes.

Eggs↗

Effect of protein concentration, pH, lactose content and pasteurization on thermal gelation of acid caprine whey protein concentrates.

The influence of pH (4.5-6.5), sodium chloride content (125-375 mM), calcium chloride content (10-30 mM), protein concentration (70-90 g/l) and lactose content on the gel hardness of goat whey protein concentrate (GWPC) in relation to the origin of the acid whey (raw or pasteurized milk) was studied using a factorial design. Gels were obtained after heat treatment (90 degrees C, 30 min). Gel hardness was measured using texture analyser. Only protein concentration and pH were found to have a statistically significant effect on the gel hardness. An increase in the protein concentration resulted in an increase in the gel hardness. GWPC containing 800g/kg protein formed gels with a hardness maximum at the pHi, whereas GWPC containing 300 g/kg protein did not form true gels. Whey from pasteurized milk formed softer gels than whey from raw milk. A high lactose content (approximately 360 g/kg) also reduced the gelation performance of GWPC.

Animals↗

Contribution of the lactoperoxidase system to the keeping quality of pasteurized milk.

The lactoperoxidase system is a naturally occurring antimicrobial system found in milk, with lactoperoxidase, thiocyanate and hydrogen peroxide as its components. The keeping quality of milk pasteurized at 72 degrees C for 15 s was found to be better than that of milk heated at 80 degrees C for 15 s. This agrees with previous findings and is usually attributed to heat shocking of spores. However, complete deactivation of lactoperoxidase occurred at 80 degrees C-15 s, whereas at 72 degrees C-15 s residual lactoperoxidase activity was approximately 70%, which may provide an alternative explanation. Higher levels of hypothiocyanite (the major antimicrobial agent produced by the lactoperoxidase system) were also detected in milk processed at 72 than at 80 degrees C, which supports the theory that the lactoperoxidase system has a role in the keeping quality of pasteurized milk. Of all the methods evaluated, titratable acidity and alcohol stability gave the most consistent estimates of keeping quality, while dissolved oxygen was a good indication of the onset of spoilage. Lactoperoxidase activity decreased with temperature more rapidly between 70 and 80 degrees C than is usual for an enzyme over a 10 deg C range.

Animals↗

Excretion of Yersinia spp. associated with consumption of pasteurized milk.

Yersinia enterocolitica biotype 1, serotype O.10K was isolated from 19 patients in the paediatric wards of a district general hospital over a period of 3 months. Fifteen cases were patients on the medical ward. Shortly afterwards, Y. enterocolitica biotype 1, serotype O.6, 30 was isolated from a further 17 patients on this ward in 1 month. The same serotypes of Y. enterocolitica were isolated from the pasteurized milk supplied to the ward. Epidemiological evidence indicated that contaminated pasteurized milk was the source of the yersinia organisms excreted by the patients.

Animals↗

Glycolysis and respiration in yeasts. The Pasteur effect studied by mass spectrometry.

Simultaneous and continuous measurements of changes in CO2 and O2 concentrations in glucose-metabolizing yeast suspensions by mass spectrometry enabled a study of the Pasteur effect (aerobic inhibition of glycolysis) in Saccharomyces uvarum and Schizosaccharomyces pombe. A different control mechanism operates in Candida utilis to give a damped oscillation after the anaerobic-aerobic transition. The apparent Km values for respiration of the three yeasts were in the range 1.3-1.8 microM-O2. The apparent Km values for O2 of the Pasteur effect were 5 and 13 microM for catabolite-repressed and derepressed S. uvarum respectively and 7 microM for Sch. pombe. These results are discussed with respect to currently accepted mechanisms for the control of glycolysis.

Candida↗

Evidence for a negative Pasteur effect in articular cartilage.

Uptake of external glucose and production of lactate were measured in freshly-excised bovine articular cartilage under O2 concentrations ranging from 21% (air) to zero (N2-bubbled). Anoxia (O2 concentration < 1% in the gas phase) severely inhibited both glucose uptake and lactate production. The decrease in lactate formation correlated closely with the decrease in glucose uptake, in a mole ratio of 2:1. This reduction in the rate of glycolysis in anoxic conditions is seen as evidence of a negative Pasteur effect in bovine articular cartilage. Anoxia also suppressed glycolysis in articular cartilage from horse, pig and sheep. Inhibitors acting on the glycolytic pathway (2-deoxy-D-glucose, iodoacetamide or fluoride) strongly decreased aerobic lactate production and ATP concentration, consistent with the belief that articular cartilage obtains its principal supply of ATP from substrate-level phosphorylation in glycolysis. Azide or cyanide lowered the ATP concentration in aerobic cartilage to approximately the same extent as did anoxia but, because glycolysis (lactate production) was also inhibited by these treatments, the importance of any mitochondrial ATP production could not be assessed. A negative Pasteur effect would make chondrocytes particularly liable to suffer a shortage of energy under anoxic conditions. Incorporation of [35S]sulphate into proteoglycan was severely curtailed by treatments, such as anoxia, which decreased the intracellular concentration of ATP.

Adenosine Triphosphate↗

Viral safety of a pasteurized, monoclonal antibody-purified factor VIII concentrate in previously untreated haemophilia A patients.

The efficacy and viral safety of a pasteurized, immunoaffinity-purified procoagulant factor VIII protein (FVIII:C; Monoclate-P) was studied in two multicentre, prospective, open-label trials in 30 previously untreated patients, 18 with severe (< 1% FVIII:C activity), and 12 with moderate (1% to 5% FVIII:C activity) haemophilia A. Clinical assessments, performed at screening and regularly thereafter for 6 to > 24 months (maximum 34 months), showed that none of 24 assessable patients acquired illnesses consistent with monitored transfusion-transmissible diseases. No patients acquired hepatitis B surface antigen, or antibodies against hepatitis B core antigen, hepatitis C, or human immunodeficiency virus. Likewise, no patients acquired treatment-related hepatitis A antibodies or sustained elevations of alanine aminotransferase levels. The safety profile for Monoclate-P is brought about by a multi-step safety system that incorporates viral inactivation (through a combination of immunoaffinity chromatography and pasteurization) plus donor screening, plasma testing, and quality assurance. The inhibitor development rate (13% low titre, 10% high titre) was similar to that reported in the literature for other FVIII concentrates (24% to 52%). The most frequently reported adverse events were related to typical infant and childhood diseases. Monoclate-P was effective in all patients treated according to protocol, except in two, who developed inhibitors.

Adolescent↗

Effect of higher pasteurization temperatures, and longer holding times at 72 degrees C, on the inactivation of Mycobacterium paratuberculosis in milk.

Raw cow's milk spiked with 10(6) cfu ml-1 of Mycobacterium paratuberculosis was subjected to heat treatments of 72, 75, 78, 80, 85 or 90 degrees C for 15 s, and 72 degrees C for 20 and 25 s, using laboratory pasteurizing units. Three bovine strains of Myco. paratuberculosis were studied (NCTC 8578, B2 and DVL 943). Each strain was subjected to all the heat treatments indicated on three separate occasions. Although each of the heat treatments achieved a substantial (5-6 log10) reduction in numbers of viable Myco. paratuberculosis, small numbers of the organism (4-16 cfu 10 ml-1) survived in a proportion of the milk samples at each of the higher temperatures investigated, right up to 90 degrees C for 15 s. A longer holding time of 25 s at 72 degrees C was found to be more effective at inactivating Myco. paratuberculosis. Only one of the three strains studied, B2, yielded small numbers of survivors after heating at 72 degrees C for 20 s, but it was completely inactivated by extending the holding time at 72 degrees C by a further 5 s to 25 s. It was concluded that a longer holding time is more likely to achieve the complete inactivation of Myco. paratuberculosis in milk than a higher pasteurization temperature.

Animals↗

Anaerobic mesophilic treatment of cattle manure in an upflow anaerobic sludge blanket reactor with prior pasteurization.

Different autonomous communities located in northern Spain have large populations of dairy cattle. In the case of Asturias, the greatest concentration of dairy farms is found in the areas near the coast, where the elimination of cattle manure by means of its use as a fertilizer may lead to environmental problems. The aim of the present research work was to study the anaerobic treatment of the liquid fraction of cattle manure at mesophilic temperature using an upflow anaerobic sludge blanket (UASB) reactor combined with a settler after a pasteurization process at 70 degrees C for 2 hr. The manure used in this study came from two different farms, with 40 and 200 cows, respectively. The manure from the smaller farm was pretreated in the laboratory by filtration through a 1-mm mesh, and the manure from the other farm was pretreated on the farm by filtration through a separator screw press (0.5-mm mesh). The pasteurization process removed the pathogenic microorganisms lacking spores, such as Enterococcus, Yersinia, Pseudomonas, and coliforms, but bacterial spores are only reduced by this treatment, not removed. The combination of a UASB reactor and a settler proved to be effective for the treatment of cattle manure. In spite of the variation in the organic loading rate and total solids in the influent during the experiment, the chemical oxygen demand (COD) of the effluent from the settler remained relatively constant, obtaining reductions in the COD of approximately 85%.

Animals↗

An outbreak of Yersinia enterocolitica O:8 infections associated with pasteurized milk.

In October 1995, an outbreak of Yersinia enterocolitica O:8 infections occurred in the Upper Valley of Vermont and New Hampshire. Ten patients were identified, median age 9 years (range, 6 months-44 years). Three patients were hospitalized; 1 underwent an appendectomy. Consumption of bottled pasteurized milk from a local dairy was associated with illness (matched odds ratio undefined; lower 95% confidence interval, 1.9). No deficiencies in pasteurization procedures or equipment were detected. Y. enterocolitica O:8 was isolated from 1 raw-milk sample and from a fecal sample from 1 dairy pig. The route of contamination was not determined; this outbreak likely resulted from postpasteurization contamination of milk. Dairy pigs were the most likely source of contamination. Milk bottles were likely contaminated by rinsing with untreated well water prior to filling or by other environmental routes. Educating dairy owners about Y. enterocolitica and postpasteurization contamination is necessary to prevent further outbreaks.

Adolescent↗

Yogurt and fermented-then-pasteurized milk: effects of short-term and long-term ingestion on lactose absorption and mucosal lactase activity in lactase-deficient subjects.

Lactase-deficient subjects absorb lactose in yogurt more effectively than lactose in other dairy products. However, as all previous studies were performed without a double-blind design and only after a single ingestion of the test product, the mechanism of this enhanced absorption remains unclear. The aims of this double-blind study were 1) to evaluate lactose absorption after prolonged ingestion of yogurt and fermented-then-pasteurized milk (FPM) and 2) to assess the modification of the lactase activity of the duodenal mucosa. In 16 lactase-deficient subjects we confirmed that yogurt enhances lactose digestion, this beneficial effect being destroyed by pasteurization. Moreover, the long-term (8 d) ingestion of either yogurt or FPM does not modify the results of hydrogen breath tests in comparison with a 24-h ingestion. The mucosal lactase (Dahlquist method) and beta-galactosidase (ONPG method) activities were not significantly modified by yogurt or FPM ingestion. These results suggest that in lactase-deficient subjects no adaptation occurs after eating yogurt or FPM and that the increased lactose absorption in yogurt must be mainly related to an intraluminal process.

Adolescent↗

D and z-values for Listeria monocytogenes and Salmonella typhimurium in packaged low-fat ready-to-eat turkey bologna subjected to a surface pasteurization treatment.

The D-values of Listeria monocytogenes and Salmonella Typhimurium at various surface pasteurization temperatures were determined for low-fat turkey bologna. Four cm2 meat squares were sterilized by irradiation prior to inoculation with 0.1 mL of a 10(8) cfu/mL culture, aseptically packaged in a linear low-density polyethylene pouch, and vacuum-sealed. Thermal treatments were administered by submerging packages in a heated water bath maintained at various set temperatures. At an 85 degrees C water bath temperature, no L. monocytogenes cells were detected (<10(2)) after 10 s of exposure, whereas at 61 degrees C cells viable were detected (>10(2)) up to 10 min of heating. No S. Typhimurium cells (<10(2)) were detected after 10 s at 70 degrees C, but cells survived up to 7 min at 60 degrees C. The D-values for L. monocytogenes at 61 and 65 degrees C were 124 and 16.2 s, respectively; whereas S. Typhimurium D-values were 278 s at 57 and 81 s at 60 degrees C. Z-values were 4.44 and 5.56 degrees C, respectively, for L. monocytogenes and S. Typhimurium. This study demonstrated that significant reductions in bacterial populations and complete inactivation of S. Typhimurium and L. monocytogenes cells can be achieved using an in-package thermal pasteurization process.

Animals↗

Thickness and compositional effects on surface heating rate of bologna during in-package pasteurization.

The surface heating rate (gamma) and final surface temperature (alpha) during in-package pasteurization were determined for different thickness levels of 2 types of bologna having different (13 and 18%) fat contents. Three thicknesses (4, 12, and 20 mm), corresponding to 1, 3, and 5 slices of bologna, were vacuum-packaged separately in a clear polymer pouch after placing a thermocouple on the surface. Refrigerated samples were immersed in a water bath set to 1 of 4 predetermined temperatures (60, 70, 80, and 90 degrees C), and time and temperature data were recorded for 10 min. Surface heating rate was fastest in the thinnest (4 mm) and slowest in the thickest (20 mm) samples for all 4 temperatures. Surface heating rate was slower in bologna with the higher fat content compared with the lower fat bologna. Final surface temperature attained after 3 min was lower with increased thickness levels for all temperatures. Thus, meat sample thickness and fat content significantly affect surface heating rate and final surface temperature during in-package pasteurization of bologna.

Animals↗

Pulmonary granulomas of guinea pigs induced by inhalation exposure of heat-treated BCG Pasteur, purified trehalose dimycolate and methyl ketomycolate.

This study was designed to determine the identity of granulomatogenic substances in Mycobacterium bovis BCG Pasteur. When heat-treated BCG Pasteur bacilli were introduced into the lungs of guinea-pigs by an inhalation exposure apparatus, pulmonary granulomas without necrosis developed. Furthermore, when four kinds of mycolates derived from M. tuberculosis Aoyama B strain were introduced into the lungs by the same method, only trehalose 6,6'-dimycolate (TDM) and methyl ketomycolate induced pulmonary granulomas without central necrosis. The pulmonary granulomas consisted of epithelioid macrophages and lymphocytes. When a mixture of TDM and anti-TDM antibody was introduced into the lungs, development of granulomatous lesions was reduced. These data indicate that TDM and methyl ketomycolate are potent granulomatogenic reagents.

Administration, Inhalation↗

Inhibiting materials for gamma phage adsorption to the cell wall of Bacillus anthracis, strain Pasteur No. 2-H.

Cell wall preparations of Bacillus anthracis, strain Pasteur No. 2-H, were treated with heat or with acetone and ether. Both of the treated cell walls preparations inactivated gamma phage. The centrifuged supernatant of the heat-treated cell walls was fractionated on Sephadex G-200, and four fractions containing reducing sugars were obtained. The first fraction had the phage-inactivating activity. On the other hand, the fourth fraction had no phage-inactivating activity, but strongly inhibited phage adsorption to the cell walls. In the fourth fraction, glutamic acid, alanine, 2,6-diaminopimelic acid and glucosamine were detected by paper chromatography after acid hydrolysis. Authentic D, L-2, 6-diaminopimelic acid and D-glucosamine markedly inhibited phage adsorption to the cell walls. D-Galactosamine, D-mannosamine and L-lysine also showed similar activities. Results suggest the possibility that one or a combination of these substances defines the characteristics of phage adsorption to the cell walls of B. anthracis, strain Pasteur No. 2-H.

Acetone↗