Evaluation of the Safety and Efficacy of a Multienzyme Complex in Patients with Functional Dyspepsia: A Randomized, Double-Blind, Placebo-Controlled Study.

Functional dyspepsia (FD) is a highly prevalent disorder having nonspecific symptoms and varied pathophysiology. Its treatment remains a challenge as therapeutic options are limited, unsatisfactory, and elusive. Thus, safety and efficacy of DigeZyme®, a proprietary multienzyme complex (MEC), was evaluated as a dietary supplement in FD patients. In this randomized, double-blind, placebo-controlled, parallel-group study, 40 patients were randomly assigned (1:1 ratio) to receive either MEC (50 mg, TID; n = 20) or placebo (n = 20) for 60 days. Reports of adverse or serious adverse events (AEs), abnormal results of vital signs, abnormal findings during physical examination, and abnormal laboratory investigations were monitored closely. Efficacy measures were change in Short-Form Leeds Dyspepsia Questionnaire (SF-LDQ), Nepean Dyspepsia Index-Short Form (NDI-SF), Visual Analog Scale (VAS), Clinical Global Impression Severity Rating Scale (CGI-S), and Glasgow Dyspepsia Severity Score (GDSS) at baseline and follow-up visits on day 15, 30, and 60. Supplementation with MEC was associated with statistically significant differences (P value ranging from .0401 to .0033) in all efficacy parameters compared with placebo. The between-group comparison also revealed that MEC supplement had a significantly greater effect (P < .001) versus placebo. No investigation product-related AEs were reported. There were no clinically significant abnormalities in physical findings and no statistically significant changes in biochemical and hematological parameters, vital signs, body weight, and body mass index observed between the two groups at baseline and follow-up visits. MEC supplementation represents an effective and safe alternative to manage dyspepsia symptoms in FD patients.

The evolution and application of enzymes in the animal feed industry: the role of data interpretation.

1. Enzymes have been used commercially for nearly 40 years and save significant costs through sparing of expensive nutrients but the mechanism by which this is achieved is still debated. 2. The research focused on non-starch polysaccharidase (NSPase) enzymes is used as an example of where greater progress could have been made if the details of the work had been described more fully and the analysis of the data generated had been broader in scope and more critical. 3. Lack of standardisation of the details presented in the materials and methods has been identified as a significant barrier to meaningful retrospective analysis and thus limits advances in the understanding of the mode of action of these enzymes. 4. The identity of the enzyme employed and its activity is often lacking, and more importantly the purity is rarely disclosed. Contaminant activities which are neither listed nor assayed could play a significant role in the responses observed. 5. The dose optimum of most enzymes is often considerably higher than that employed in most studies. Thus studies claiming synergy between two 'activities' should ensure that the response is not related to each enzyme simply augmenting the dose of just one activity in the finished feed. This is a common problem, and coupled with the lack of factorial experiments to justify the presence of each enzyme in a multi-enzyme product, it is not surprising that there is still debate as to whether single or multi-enzymes are best suited poultry rations. 6. The three proposed mechanisms for NSPases (viscosity, cell wall and prebiotic) are discussed, and along with their strengths and weaknesses it is suggested that a re-evaluation of each is needed. Viscosity may have to be re-evaluated as being a function not only of the cereal being fed, but of the age of the animal as well. The cell wall theory as described is poorly modelled in vitro and hence the validity of these data is questioned. The prebiotic theory may need significant modification as it appears that the quantities of oligomers produced are insufficient to generate the additional volatile fatty acids (VFA)'s reported. It is likely that all three mechanisms play a role in the responses observed, but the prebiotic mechanism probably plays by far the most important part in low viscosity diets. 7. Future research would be improved if it considered all potential mechanisms when designing a trial. Significant failings are apparent as a result of adherence to tenets in explanation of the results. Most importantly, it should be emphasised that a hypothesis is there to be tested, not defended.

Sensitising effects of genetically modified enzymes used in flavour, fragrance, detergence and pharmaceutical production: cross-sectional study.

OBJECTIVES: The use of genetically engineered enzymes in the synthesis of flavourings, fragrances and other applications has increased tremendously. There is, however, a paucity of data on sensitisation and/or allergy to the finished products. We aimed to review the use of genetically modified enzymes and the enormous challenges in human biomonitoring studies with suitable assays of specific IgE to a variety of modified enzyme proteins in occupational settings and measure specific IgE to modified enzymes in exposed workers. METHODS: Specific IgE antibodies against workplace-specific individual enzymes were measured by the specific fluorescence enzyme-labelled immunoassay in 813 exposed workers seen in cross-sectional surveys. RESULTS: Twenty-three per cent of all exposed workers showed type I sensitisation with IgE antibodies directed against respective workplace-specific enzymes. The highest sensitisation frequencies observed were for workers exposed enzymes derived from α-amylase (44%), followed by stainzyme (41%), pancreatinin (35%), savinase (31%), papain (31%), ovozyme (28%), phytase (16%), trypsin (15%) and lipase (4%). The highest individual antibody levels (up to 110 kU/L) were detected in workers exposed to phytase, xylanase and glucanase. In a subgroup comprising 134 workers, detailed clinical diagnostics confirmed work-related symptoms. There was a strong correlation (r=0.75, p<0.0001) between the symptoms and antibody levels. Workers with work-related respiratory symptoms showed a higher prevalence for the presence of specific IgE antibodies against workplace-specific enzymes than asymptomatic exposed workers (likelihood ratio 2.32, sensitivity 0.92, specificity 0.6). CONCLUSIONS: Our data confirm the previous findings showing that genetically engineered enzymes are potent allergens eliciting immediate-type sensitisation. Owing to lack of commercial diagnostic tests, few of those exposed receive regular surveillance including biomonitoring with relevant specific IgE assays.

Amino acid deprivation using enzymes as a targeted therapy for cancer and viral infections.

INTRODUCTION: Amino acid depletion in the blood serum is currently being exploited and explored for therapies in tumors or viral infections that are auxotrophic for a certain amino acid or have a metabolic defect and cannot produce it. The success of these treatments is because normal cells remain unaltered since they are less demanding and/or can synthesize these compounds in sufficient amounts for their needs by other mechanisms. Areas covered: This review is focused on amino acid depriving enzymes and their formulations that have been successfully used in the treatment of several types of cancer and viral infections. Particular attention will be given to the enzymes L-asparaginase, L-arginase, L-arginine deiminase, and L-methionine-γ-lyase. Expert opinion: The immunogenicity and other toxic effects are perhaps the major limitations of these therapies, but they have been successfully decreased either through the expression of these enzymes from other organisms, recombination processes, pegylation of the selected enzymes or by specific mutations in the proteins. In 2006, FDA has already approved the use of L-asparaginase in the treatment of acute lymphoblastic leukemia. Other enzymes and in particular L-arginase, L-arginine deiminase, and L-methioninase have been showing promising results in vitro and in vivo studies.

IgE-Mediated Hypersensitivity and Desensitisation with Recombinant Enzymes in Pompe Disease and Type I and Type VI Mucopolysaccharidosis.

Enzyme replacement therapy (ERT) is important for the treatment of lysosomal storage disorders. Hypersensitivity reactions with ERT have been reported, and in these cases, desensitisation with the enzyme is necessary. Here we report the cases of 3 patients with lysosomal storage disorders, including Pompe disease and mucopolysaccharidosis type I and VI, who had IgE-mediated hypersensitivity reactions and positive skin tests. Successful desensitisation protocols with the culprit enzyme solution were used for these patients. All 3 patients were able to safely receive ERT with the desensitisation protocol.

Prevalence of sensitization to 'improver' enzymes in UK supermarket bakers.

BACKGROUND: Supermarket bakers are exposed not only to flour and alpha-amylase but also to other 'improver' enzymes, the nature of which is usually shrouded by commercial sensitivity. We aimed to determine the prevalence of sensitization to 'improver' enzymes in UK supermarket bakers. METHODS: We examined the prevalence of sensitization to enzymes in 300 bakers, employed by one of two large supermarket bakeries, who had declared work-related respiratory symptoms during routine health surveillance. Sensitization was determined using radioallergosorbent assay to eight individual enzymes contained in the specific 'improver' mix used by each supermarket. RESULTS: The prevalence of sensitization to 'improver' enzymes ranged from 5% to 15%. Sensitization was far more likely if the baker was sensitized also to either flour or alpha-amylase. The prevalence of sensitization to an 'improver' enzyme did not appear to be related to the concentration of that enzyme in the mix. CONCLUSIONS: We report substantial rates of sensitization to enzymes other than alpha-amylase in UK supermarket bakers; in only a small proportion of bakers was there evidence of sensitization to 'improver mix' enzymes without sensitization to either alpha-amylase or flour. The clinical significance of these findings needs further investigation, but our findings indicate that specific sensitization in symptomatic bakers may not be identified without consideration of a wide range of workplace antigens.

Efficacy of chelation therapy to remove aluminium intoxication.

There is a distinct correlation between aluminium (Al) intoxication and neurodegenerative diseases (ND). We demonstrated how patients affected by ND showing Al intoxication benefit from short-term treatment with calcium disodium ethylene diamine tetraacetic acid (EDTA) (chelation therapy). Such therapy further improved through daily treatment with the antioxidant Cellfood. In the present study we examined the efficacy of long-term treatment, using both EDTA and Cellfood. Slow intravenous treatment with the chelating agent EDTA (2 g/10 mL diluted in 500 mL physiological saline administered in 2 h) (chelation test) removed Al, which was detected (using inductively coupled plasma mass spectrometry) in urine samples collected from patients over 12 h. Patients that revealed Al intoxication (expressed in µg per g creatinine) underwent EDTA chelation therapy once a week for ten weeks, then once every two weeks for a further six or twelve months. At the end of treatment (a total of 22 or 34 chelation therapies, respectively), associated with daily assumption of Cellfood, Al levels in the urine samples were analysed. In addition, the following blood parameters were determined: homocysteine, vitamin B12, and folate, as well as the oxidative status e.g. reactive oxygen species (ROS), total antioxidant capacity (TAC), oxidized LDL (oxLDL), and glutathione. Our results showed that Al intoxication reduced significantly following EDTA and Cellfood treatment, and clinical symptoms improved. After treatment, ROS, oxLDL, and homocysteine decreased significantly, whereas vitamin B12, folate and TAC improved significantly. In conclusion, our data show the efficacy of chelation therapy associated with Cellfood in subjects affected by Al intoxication who have developed ND.

Enzymes approved for human therapy: indications, mechanisms and adverse effects.

Research and drug developments fostered under orphan drug product development programs have greatly assisted the introduction of efficient and safe enzyme-based therapies for a range of rare disorders. The introduction and regulatory approval of 20 different recombinant enzymes has enabled, often for the first time, effective enzyme-replacement therapy for some lysosomal storage disorders, including Gaucher (imiglucerase, taliglucerase, and velaglucerase), Fabry (agalsidase alfa and beta), and Pompe (alglucosidase alfa) diseases and mucopolysaccharidoses I (laronidase), II (idursulfase), IVA (elosulfase), and VI (galsulfase). Approved recombinant enzymes are also now used as therapy for myocardial infarction (alteplase, reteplase, and tenecteplase), cystic fibrosis (dornase alfa), chronic gout (pegloticase), tumor lysis syndrome (rasburicase), leukemia (L-asparaginase), some collagen-based disorders such as Dupuytren's contracture (collagenase), severe combined immunodeficiency disease (pegademase bovine), detoxification of methotrexate (glucarpidase), and vitreomacular adhesion (ocriplasmin). The development of these efficacious and safe enzyme-based therapies has occurred hand in hand with some remarkable advances in the preparation of the often specifically designed recombinant enzymes; the manufacturing expertise necessary for commercial production; our understanding of underlying mechanisms operative in the different diseases; and the mechanisms of action of the relevant recombinant enzymes. Together with information on these mechanisms, safety findings recorded so far on the various adverse events and problems of immunogenicity of the recombinant enzymes used for therapy are presented.

Over-the-counter enzyme supplements: what a clinician needs to know.

Over-the-counter (OTC) enzyme use is increasing in frequency in the United States. The numerous health benefit claims by manufacturers are leading to a surge in enzyme use for various conditions and symptoms. Clinicians need to help patients navigate this complex realm and make informed decisions about the use of OTC enzymes. This review focuses on key concepts for health care providers to understand the current evidence, risks, and benefits of OTC enzymes.

GlucoMen Day continuous glucose monitoring system: a screening for enzymatic and electrochemical interferents.

BACKGROUND: While most of the common drugs with the potential to interfere with continuous glucose monitoring (CGM) systems are accessible over the counter and can be assumed by CGM patients without medical supervision, many other chemicals are frequently used to treat critically ill patients. Continuous glucose monitoring reading accuracy may also be compromised in patients characterized by abnormally high concentrations of physiological interferents. In this article, 22 species selected from endogenous and exogenous chemicals were screened as possible interferents of GlucoMen®Day (GMD), the new microdialysis-based CGM system from A. Menarini Diagnostics. METHOD: Interference testing was performed according to the EP7-A2 guideline (Clinical and Laboratory Standards Institute 2005). Interference was evaluated at two levels of glucose, with each interferent additionally tested at two concentrations. Furthermore, two configurations of the GMD disposable sensor kit--one designed for subcutaneous application, the other for direct intravascular CGM--were challenged with interferent-spiked serum and blood samples, respectively. RESULTS: With the exception of dopamine (however, at very high, nonphysiological concentrations), no interference was observed for all the tested substances. Interestingly, none of the common electrochemical interferents (including ascorbic acid, acetaminophen, and salicylic acid, which represent the major specificity issue for the competing CGM systems) significantly affected the system's output. CONCLUSIONS: These results provide clear insights into the advantages offered by the use of a microdialysis-based CGM system that additionally relies on the detection of hydrogen peroxide at low operating potential. GlucoMen Day may become the CGM system of choice for those patients who require either regular administration of drugs or their glycemia to be tightly controlled in the intensive care unit or similar environments.

Occupational risk factors associated with work-exacerbated asthma in Quebec.

BACKGROUND: There is limited information regarding the occupational exposures of subjects with a diagnosis of work-exacerbated asthma (WEA). OBJECTIVES: To: (1) identify potential specific occupational, chemical, biological and physical agents associated with incident cases of WEA and (2) compare these agents with occupational exposures of occupational asthma (OA) and non-work-related asthma (NWRA) cases. METHODS: Subjects were workers with work-related asthma (WRA) or NWRA referred between 2005 and 2008 to two Quebec clinics specialised in the field of WRA. Specific inhalation challenges were performed to differentiate OA from WEA. Work exposures were assessed using a detailed occupational questionnaire. Exposures to 41 chemical and biological agents were coded in a semiquantitative way according to a combination of indices for concentration in workplace air, frequency and confidence of exposure by an occupational hygienist expert in occupational exposure coding. This expert was blind to the medical status of WEA, OA or NWRA. Five physical agents were coded on a yes/no scale. RESULTS: 153 subjects were enrolled (53 WEA, 67 OA and 33 NWRA). WEA cases were significantly more exposed to ammonia, engine exhaust fumes, silica, mineral fibres, aerosol propellants and solvents, and significantly less exposed to animal derived dust and enzymes than were OA cases. Exposure to physical conditions did not differ between WEA and OA. CONCLUSIONS: Exposures associated with WEA differ from those associated with OA in this study. A proportion of subjects with WEA may suffer from low-dose irritant asthma, which remains a hypothesis to be tested.

Relevance of sensitization to occupational allergy and asthma in the detergent industry.

There exists considerable historic experience of the relationship between exposure and both the induction of sensitization and the elicitation of respiratory symptoms from industrial enzymes of bacterial and fungal origin used in a wide variety of detergent products. The detergent industry in particular has substantial experience of how the control of exposure leads to limitation of sensitization with low risk of symptoms. However, the experience also shows that there are substantial gaps in knowledge, even when the potential occupational allergy problem is firmly under control, and also that the relationship between exposure and sensitization can be hard to establish. The latter aspect includes a poor appreciation of how peak exposures and low levels of exposure over time contribute to sensitization. Furthermore, while a minority of workers develop specific IgE, essentially none appear to have symptoms, a situation which appears to contradict the allergy dogma that, once sensitized, an individual will react to much lower levels of exposure. For enzymes, the expression of symptoms occurs at similar or higher levels than those that cause induction. In spite of some knowledge gaps, medical surveillance programs and constant air monitoring provide the tools for successful management of enzymes in the occupational setting. Ultimately, the knowledge gained from the occupational setting facilitates the completion of safety assessments for consumer exposure to detergent enzymes. Such assessments have been proven to be correct by the decades of safe use both occupationally and in consumer products.

The toxicology and immunology of detergent enzymes.

Detergent enzymes have a very good safety profile, with almost no capacity to generate adverse acute or chronic responses in humans. The exceptions are the limited ability of some proteases to produce irritating effects at high concentrations, and the intrinsic potential of these bacterial and fungal proteins to act as respiratory sensitizers, demonstrated in humans during the early phase of the industrial use of enzymes during the 1960s and 1970s. How enzymes generate these responses are beginning to become a little clearer, with a developing appreciation of the cell surface mechanism(s) by which the enzymatic activity promotes the T-helper (T(H))-2 cell responses, leading to the generation of IgE. It is a reasonable assumption that the majority of enzyme proteins possess this intrinsic hazard. However, toxicological methods for characterizing further the respiratory sensitization hazard of individual enzymes remains a problematic area, with the consequence that the information feeding into risk assessment/management, although sufficient, is limited. Most of this information was in the past generated in animal models and in vitro immunoassays that assess immunological cross-reactivity. Ultimately, by understanding more fully the mechanisms which drive the IgE response to enzymes, it will be possible to develop better methods for hazard characterization and consequently for risk assessment and management.

Cellfood™ improves respiratory metabolism of endothelial cells and inhibits hypoxia-induced reactive oxygen species (ros) generation.

Endothelial mitochondria, the major site of ATP generation, modulate the intracellular dynamics of reactive oxygen species (ROS), which, in turn, control endothelial function. Adequate oxygen (O(2)) supply is required by endothelial cells (EC). Both hypoxia and hyperoxia may favor the overproduction of ROS leading to oxidative stress, mitochondrial damage and endothelial dysfunction. We investigated the capability and mechanisms of Cellfood™ (CF), an antioxidant compound, to modulate O(2) availability and mitochondrial respiratory metabolism and to regulate ROS generated by hypoxia in EC in vitro. Human umbilical vein endothelial cells (HUVEC) and ECV-304 were evaluated for the O(2) consumption using a Clark's electrode. The O(2) consumption rate rose, during the first minutes after CF addition and was associated with increase in mitochondrial oxidative capacity and good cell viability. Similar behaviours were observed when EC were exposed to CF for up to 8 days. The O(2) consumption increased and was accompanied by both intracellular rise of ATP and maintainment of LDH concentration. Hypoxia-induced ROS generation was significantly inhibited by CF, through the up-regulated expression of MnSOD, an anti-oxidant responsible for mitochondrial function preservation. The EC hypoxic response is mediated by the hypoxia master regulator HIF-1alpha whose activation was attenuated by CF, in concomitance with MnSOD up-regulation. Our results suggest a role for CF in improoving respiratory metabolism and in activating anti-oxidant mechanisms in EC, thus preserving endothelial function.

Occupational asthma and rhinitis due to detergent enzymes in healthcare.

BACKGROUND: The use of proteolytic enzymes to improve the cleaning efficacy of washing powders was introduced in the mid 1960s. Many microbial enzymes are known to be potent respiratory sensitizers but previously there has been only one case of occupational asthma associated with workplace exposure in a healthcare worker. AIMS: To report two cases of occupational asthma associated with exposure to biological enzymes in health-care workers and related occupational cases. METHODS: Reporting of clinical case reports from three different work places. RESULTS: One case of occupational asthma and three other cases with work-related asthma or rhinitis occurred in one workplace. A single case of probable occupational asthma presented at a second workplace with another case of work-related asthma at a third workplace. Exposures occurred in areas used for cleaning medical instruments and endoscopy suites. Hygiene measurements confirmed the potential for exposure. Control measures were not in place and recognition of the hazard was missing in these workplaces. CONCLUSIONS: Detergent enzymes when used in healthcare settings should be recognized as potential respiratory sensitizers. Healthcare institutions and professional bodies that recommend the use of detergent enzymes should review their risk assessments to ensure that the most appropriate methods for preventing or reducing exposure are in place.

Relationship of mammalian erythrocyte enzymesand their intermediary compounds among selected animals / Correlação of enzimas eritrocitárias e seus compostos intermediários de mamíferos selecionados

As there are few comparative studies on mammalian red cell metabolism, it was decided to study the glycolytic enzyme activities aswell as related ones, and the metabolites adenosine-5´-triphosphate(ATP) and 2,3-bisphosphoglycerate (2,3-BPG). Mammalia representatives from Primates, Rodentia, Carnivora, Lagomorpha,Artyodactyla, Didelphimorphia and Xenarthra orders, obtained from Fundação Parque Zoológico de São Paulo and Centro de Bioterismoda Faculdade de Medicina da USP, were studied. The blood was collectedin EDTA and ACD, the red cells were washed in saline at 4o C, lysed1:20 in hemolysing solution by freeze-and-thaw, and the followingenzymes were assayed according to standard procedures: hexokinase,glucose-6-phosphate isomerase, phosphofructokinase, aldolase, triosephosphate isomerase, glyceraldehyde-3-phosphate dehydrogenase,phosphoglycerate kinase, monophosphoglycerate mutase, enolase,pyruvate kinase, lactate dehydrogenase, as well as 2,3-bisphosphoglycerate mutase, glucose-6-phosphate dehydrogenase,6-phosphogluconate dehydrogenase activities at 37oC , and adenosine-5´-triphosphate and 2,3-bisphophoglycerate concentrations. Are markable variation among the studied species was observed.However, it was detected a significant positive correlation between the adenosine-5´-triphosphate concentrations and triose phosphate isomerase and 2,3-bisphosphoglycerate mutase activities, as well assignificant positive correlation between 2,3-bisphosphoglycerate concentration and 2,3-bisphosphoglycerate mutase activity in all studied species as a whole. Most of studied species exhibited a steady ATP concentration range between 4 and 6 μ moles.g Hb –1 except the Artiodactyla (Cervus elaphus) and Carnivora (Panthera leo, Leoparduspardalis, Canis Lupus and Chrysocyon brachyurus,) which presented values between 2 and 3 μ moles g Hb –1. However, the 2,3-BPG concentration showed remarkable variation among the studied ...

Como há poucos estudos comparativos sobre o metabolismo eritrócitário dos mamíferos propôs-se estudar as atividades das enzimas glicolíticas, anexas e os metabólitos adenosina-5’-trifosfato e2,3-difosfoglicerato. Foram estudados mamíferos das ordens Primata,Rodentia, Carnivora, Lagomorpha, Artiodactyla, Didelphimorphia eXenarthra oriundos da Fundação Parque Zoológico de São Paulo e Centro de Bioterismo da Faculdade de Medicina da USP. O sangue foicolhido em EDTA e ACD, os eritrócitos foram lavados em soluçãofisiológica a 4o C e hemolisados em solução hemolisante 1:20 porcongelamento e descongelamento e as atividades das seguintes enzimasforam determinadas de acordo com procedimentos padronizados:hexoquinase, glicose-6-fosfato isomerase , fosfofrutoquinase, aldolase,triose fosfato isomerase, gliceraldeído-3-fosfato desidrogenase,fosfoglicerato quinase, 2,3-difosfoglicerato mutase,monofosfogliceromutase, enolase, piruvato quinase, lactatodesidrogenase, bem como a glicose-6-fosfato desidrogenase, 6-fosfogluconato desidrogenase a 37ºC e os metabólitos intermediários2,3-difosfoglicerato e adenosina-5’-trifosfato. As enzimas e os compostos intermediários estudados apresentaram grande variabilidade entre as espécies de mamíferos estudadas. Foi observada correlação positiva entre a atividade da triose fosfato isomerase e a 2,3-difosfoglicerato mutase e os teores de adenosina-5’-trifosfato das espécies, bem como correlação positiva entre a 2,3-difosfogliceratomutase em relação ao 2,3-difosfoglicerato. Os teores de adenosina-5’-trifosfato mantiveram-se dentro de uma faixa estável, ao redor de 4 a6 μ moles / gHb, com as exceções das espécies das ordens Carnivora(Panthera leo, Leopardus pardalis, Canis lupus and Chrysocyonbrachyurus) e Artiodactyla (Cervus elaphus), que exibiram 2 a 3 μmoles / g Hb. Já os valores da concentração de 2,3-difosfoglicerato apresentaram, por sua vez, variação considerável entre as..

Utilização do triticale e de enzimas em dietas para suínos: digestibilidade e metabolismo / Utilization of triticale and of enzymes in pig diets: digestibility and metabolism

Avaliou-se o efeito da inclusão de níveis de triticale sobre o valor nutritivo de dietas para suínos com ou sem enzimas. Foram utilizados 24 suínos machos, castrados, com peso inicial de 59kg, alojados em gaiolas metabólicas. O delineamento foi de blocos ao acaso em arranjo fatorial 3 x 2 (níveis de triticale, 0, 30 e 60 por cento, com ou sem enzimas), com quatro repetições cada. A inclusão de triticale na dieta em até 60 por cento e a adição de enzimas não influenciou (P>0,05) a digestibilidade da matéria seca, fósforo, energia bruta, metabolização da energia, energia digestível e metabolizável e o balanço do N. Os valores médios de energia digestível e metabolizável foram de 3.537 e 3.435kcal. Houve interação triticale x enzimas na proteína digestível aparente (PDa) (P<0,01). Na dieta com 60 por cento de triticale sem adição de enzimas a PDa foi 6 por cento inferior à controle. Na dieta com 30 e 60 por cento de triticale com enzimas, a PDa foi similar à controle e 5 por cento superior à dieta com 60 por cento de triticale sem enzimas. A inclusão de 60 por cento de triticale em dietas para suínos reduz a PDa. A adição de enzimas melhora a PDa em dietas com 30 e 60 por cento de triticale.

The effect of triticale levels with or without enzyme supplementation on nutritive value of pig's diet was evaluated using twenty four barrows weighting 59kg, housed in metabolic crates. A complete randomized experimental block design in a 3 x 2 factorial arrangement (triticale levels -0, 30 e 60 percent with or without enzymes) with four replicates each was utilized. No effects of triticale levels and enzymes supplementation (P>0.05) were observed on dry matter digestibility, phosphorus, crude energy, metabolization of energy, digestible and metabolizable energy and nitrogen balance. The average values of digestible and metabolizable energy were 3,537 e 3,435kcal. An interaction triticale x enzymes effect on apparent digestible protein (DPa) (P<0.01) was observed. Apparent digestible protein for 60 percent triticale diets without enzymes supplementation was 6 percent lower than control diet while DPa of 30 and 60 percent triticale diets with enzymes supplementation were similar to DPa of the control diet and 5 percent higher than 60 percent triticale diets without enzyme supplementation. The inclusion of 60 percent triticale in pig diets reduces the DPa. Enzymes supplementation improves the DPa for diets containing 30 and 60 percent of triticale.

Enzymes, trophoblasts, and cancer: the afterlife of an idea (1924-2008).

In the early 20th century, advocacy of the enzyme therapy of cancer was primarily the work of one man, John Beard, DSc (1858-1924). He and his collaborators made a determined effort to establish this mode of therapy, especially in the years 1905 to 1911. Despite a brief flowering of international interest, Beard's efforts came to naught. During the 20th century, there was a succession of American researchers who continued to investigate this topic. This included Marshall William McDuffie, MD (1882-1945), Frank LeForest Morse, MD (1876-1953), Franklin Lloyd Shively, MD (1887-1971), and William Donald Kelley (1926-2005). In central Europe, India, and other parts of the globe, the use of pancreatic enzymes as an adjuvant treatment for cancer has become a fairly routine practice, at least among those doctors who utilize complementary and alternative medicine (CAM). It is also a well-established method for reducing inflammation and mitigating the adverse effects of cytotoxic treatment.

Investigation on possible allergenicity of 19 different commercial enzymes used in the food industry.

The aim of the study was to investigate the safety to allergic patients of 19 commercially available and authority-approved enzymes used in the food industry. Enzymes produced by genetically modified organisms were included. Four hundred consecutive adult patients with a diagnosed allergy to inhalation allergens, food allergens, bee or wasp were included. All had at least one positive skin prick test to the above allergens. Skin prick testing with the 19 enzymes was performed on the forearm and if positive (in 13 patients), in vitro histamine release from blood basophils were performed. Patients with positive results in skin prick test were subsequently reinvestigated with further purified enzymes and finally challenged orally with the enzymes in a double-blind, placebo-controlled protocol. Only one reaction to a placebo challenge was seen. In some instances a positive skin prick test result or a positive histamine release was seen elicited by the enzymes, but since none of the patients were positive to any of the commercial enzymes in the subsequent oral challenges using exaggerated dosages of the enzymes compared to normal daily intake, the findings are without clinical relevance. A wide variety of enzyme classes and origins was included in the study. Because there were no allergenic findings of clinical relevance it is concluded that ingestion of food enzymes in general is not considered to be a concern with regard to food allergy.