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PubMed2006

Nutrient cycling by fish supports relatively more primary production as lake productivity increases.

Animals can be important in nutrient cycling in particular ecosystems, but few studies have examined how this importance varies along environmental gradients. In this study we quantified the nutrient cycling role of an abundant detritivorous fish species, the gizzard shad (Dorosoma cepedianum), in reservoir ecosystems along a gradient of ecosystem productivity. Gizzard shad feed mostly on sediment detritus and excrete sediment-derived nutrients into the water column, thereby mediating a cross-habitat translocation of nutrients to phytoplankton. We quantified nitrogen and phosphorus cycling (excretion) rates of gizzard shad, as well as nutrient demand by phytoplankton, in seven lakes over a four-year period (16 lake-years). The lakes span a gradient of watershed land use (the relative amounts of land used for agriculture vs. forest) and productivity. As the watersheds of these lakes became increasingly dominated by agricultural land, primary production rates, lake trophic state indicators (total phosphorus and chlorophyll concentrations), and nutrient flux through gizzard shad populations all increased. Nutrient cycling by gizzard shad supported a substantial proportion of primary production in these ecosystems, and this proportion increased as watershed agriculture (and ecosystem productivity) increased. In the four productive lakes with agricultural watersheds (>78% agricultural land), gizzard shad supported on average 51% of phytoplankton primary production (range 27-67%). In contrast, in the three relatively unproductive lakes in forested or mixed-land-use watersheds (>47% forest, <52% agricultural land), gizzard shad supported 18% of primary production (range 14-23%). Thus, along a gradient of forested to agricultural landscapes, both watershed nutrient inputs and nutrient translocation by gizzard shad increase, but our data indicate that the importance of nutrient translocation by gizzard shad increases more rapidly. Our results therefore support the hypothesis that watersheds and gizzard shad jointly regulate primary production in reservoir ecosystems.

Animals↗
PubMed1999

Why promote campaigns for clean products and clean production?

Environmental advocacy in the United States has focused on controlling pollution and waste through a system based on government permits for managing the release of environmental pollutants. The conventional focus on pollution control and waste management has been less than comprehensive. From an ecological perspective it makes little sense to focus on reducing environmental pollution from the waste pipe of industrial facilities while ignoring those same pollutants when inside the plant or sent out the product door. But an ecological perspective is not the same as a political perspective. The focus on pollution and waste has achieved legitimacy; focusing on production appears to invite an invasion of private property, a sensitive issue for most businesses. Discussing the constituents and volume of products treads on issues many think should best be reserved for the market. Focusing on production and products requires technical knowledge and skills not conventionally found in environmental advocacy organizations. Why should environmental or occupational health advocates stretch their conventional domain? Here is an argument for products and production, listing ten reasons for campaigning on clean production and products.

Journal Article↗
PubMed1992

Interrelationships of heifer milk production and other biological traits with production efficiency to weaning.

Interrelationships among milk production, dam-calf feed efficiency to weaning, and other biological traits were evaluated on 411 first-calf heifers and their calves. Individual feed intakes were measured in a drylot environment for a 1-yr period until weaning of the first calf. Heifer breed types included crossbred Angus-Hereford, Simmental-Hereford, and Tarentaise-Hereford produced in two-breed rotational crossbreeding systems, F1 Salers-Hereford and straightbred Hereford. Production efficiency was defined as cumulative feed ME consumed by the dam-calf pair during the year divided by calf weaning weight. Milk production potential seemed to be unrelated to cow size, adjusted for breed-group effects. Lactational feed energy was increased for dams of increased milk production potential but not enough to offset the increased production of calf weaning weight in terms of production efficiency. Results indicated that increased levels of milk production of heifers were associated with improved production efficiency to weaning. However, the incremental improvement in efficiency per unit of increased milk was less for each additional unit of milk, within the range evaluated. These results are applicable to first-calf heifers that have not yet reached peak age for maximum milk production.

Animals↗
PubMed1991

Analysis of the time course of IFN-gamma mRNA and protein production during primary murine listeriosis. The immune phase of bacterial elimination is not temporally linked to IFN production in vivo.

IFN-gamma clearly plays an important role in the murine host response against Listeria monocytogenes, but the time course of its production and its precise role in immunity remain controversial. To address these issues, we sequentially monitored IFN production and bacterial accumulation in vivo in C57B1/6 mice during primary listeriosis. IFN-gamma mRNA levels (measured by Northern blot analysis of freshly isolated splenic RNA) and serum IFN (measured by ELISA) were both maximal on day 1 of infection, decreasing steadily after day 2 to barely detectable levels by days 4 to 6. Significantly, there was no direct relationship between IFN levels and listericidal activity in vivo. Between days 1 and 3, the period of maximal IFN production, host bacterial load (assessed by quantitating live L. monocytogenes/spleen) increased approximately 10- to 50-fold. On the other hand, during the immune phase of infection (between days 5 and 7), a period when both IFN mRNA and protein were barely detectable, the host bacterial load decreased 1,000- to 10,000-fold. The paucity of IFN production in vivo during the immune phase was unexpected in light of previous reports demonstrating abundant in vitro lymphokine release by splenocytes isolated during the same time period. By direct comparisons of IFN production in vivo and in vitro, however, we could show that the late (days 6-7) peak of IFN release observed in Ag-stimulated cultures was an in vitro artifact. By contrast the pattern of spontaneous IFN release (obtained when freshly isolated cells were incubated in the absence of Ag) conformed more closely to that observed in vivo. Because listerial Ag stimulated vigorous lymphokine release in vitro, we sought to determine whether an analogous effect could be observed in vivo. In fact, even the infusion of very large doses of live bacteria (5-20,000,000/mouse) did not stimulate endogenous IFN-gamma production in mice infected for 6 to 7 days. These studies suggest three major conclusions: 1) IFN production in vivo occurs primarily during the early phase of listeriosis; 2) the dramatic decrease in bacterial numbers observed late in infection cannot be directly attributed to increased IFN production by LM-immune T cells; 3) although Ag-driven cultures of freshly isolated cells can provide useful information about the potential lymphokine-producing capabilities of Ag-specific T cells, these results have limited relevance in understanding patterns of T cell lymphokine production in vivo.

Animals↗
PubMed1993

Dissociation of platelet-activating factor production and arachidonate release by the endomembrane Ca(2+)-ATPase inhibitor thapsigargin. Evidence for the involvement of a Ca(2+)-dependent route of priming in the production of lipid mediators by human polymorphonuclear leukocytes.

The production of platelet-activating factor (PAF) and the release of [3H]arachidonate were studied in human polymorphonuclear leukocytes (PMN) stimulated with thapsigargin, an inhibitor of endomembrane Ca(2+)-ATPase. Concentrations of thapsigargin as low as 10-25 nM primed PMN for both PAF production and [3H]arachidonate release in response to the chemotactic peptide (fMLP), whereas concentrations in the range 25-200 nM induced a time- and dose-dependent production of PAF, which occurred in the absence of both [3H]arachidonate release and [3H]phosphatidylethanol formation. Studies in fura-2/AM-loaded cells showed that concentrations of thapsigargin that elicited PAF production induced a protracted and long lasting elevation of cytosolic free calcium concentration ([Ca2+]i) between 200 and 700 nM. The lower concentrations primed the cells for a late [Ca2+]i elevation in response to fMLP similar to that elicited by cytochalasin B or ionomycin. PAF production showed a good correlation with the increase of [Ca2+]i (r = 0.91) irrespective of the procedure used to grade [Ca2+]i. In contrast, phorbol 12,13-dibutyrate failed to induce both PAF production and elevation of [Ca2+]i, but it was a very effective stimulator of [3H]arachidonate release and [3H]phosphatidylethanol production. These data indicate that PAF production and [3H]arachidonate release in PMN differ in both biochemical pathway and modulatory mechanisms. Whereas PAF production seems extremely sensitive to changes in [Ca2+]i, which seems to exert its modulatory effect at the lyso-PAF:acetyl-CoA acetyltransferase step, [3H]arachidonate release seems tightly modulated by protein kinase C-dependent mechanisms and is coincidental with activation of phospholipase D.

Arachidonic Acid↗
PubMed1996

Renal tubular epithelial cell-E. coli interaction products stimulate nitric oxide production in cultured rat renal medullary interstitial and mesangial cells.

Tubulointerstitial and periglomerular inflammation and fibrosis are important consequences of pyelonephritis. The pathogenesis of these abnormalities is not fully understood. Renal tubular epithelial cells (RTEC) elaborate biologically active materials following incubation with bacteria. Nitric oxide (NO) is an inflammatory mediator and it modulates the accumulation of extracellular matrix proteins. Therefore, we studied whether RTEC-E. coli interaction products regulate NO production by cultured rat renal medullary interstitial cells (RMIC) and mesangial cells (MC). RMIC and MC were maintained in media containing IFN-gamma and LPS for 24-72 h. Test media contained either no further additives or 20% supernatants from RTEC incubated with E. coli or bacterial cell products. RTEC-E. coli interaction products significantly increased NO production in RMIC and MC. This stimulation in NO production was not associated with changes in inducible nitric oxide synthase (iNOS) gene or protein expression. These findings indicate that RTEC-E. coli interaction products increase NO production in RMIC and MC by directly stimulating iNOS enzymatic activity. Altered NO production by renal cells may contribute to tubulointerstitial inflammation in acute and chronic pyelonephritis.

Animals↗
PubMed1998

Cytokine production and surface marker expression in acute and stable multiple sclerosis: altered IL-12 production and augmented signaling lymphocytic activation molecule (SLAM)-expressing lymphocytes in acute multiple sclerosis.

Ag-stimulated IL-2 production and mitogen-stimulated type 1 and type 2 cytokine production by PBMC, as well as expression of Th1- and Th2-associated phenotypical markers, of B7-1, B7-2, and CD95 (Fas) on the surface of immune cells, and the serum concentration of soluble Apo-1/Fas were evaluated in multiple sclerosis (MS) patients with either acute (AMS) or stable (SMS) disease and in healthy controls (HC). Results showed that 1) Ag-stimulated IL-2 production is reduced in MS patients compared with that in HC; 2) mitogen-stimulated type 1 cytokine production is increased, and IL-10 production is reduced in MS patients compared with those in HC, and in AMS patients compared with those in SMS; 3) whereas production of the metabolically active p70 heterodimers is comparable in SMS, AMS, and HC, production of the p70 heterodimer and the p40 chains (total IL-12) is increased in SMS compared with that in AMS and HC; 4) CD4+, CD4+ SLAM+, and CD4+ CD7+ lymphocytes (preferentially type 1 cytokine-producing lymphocytes) are increased in MS compared with levels in HC; 5) B7-2- as well as Fas+-expressing monocytes are augmented in MS compared with those in HC, and serum soluble Apo-1/Fas is augmented in AMS compared with SMS and HC. These results confirm that a complex imbalance in both cytokine production and the Fas system is present in MS and indicate that different cytokine profiles may be observed in patients with acute or stable disease. The data also suggest that peculiar phenotypic populations are over-represented in MS patients, and for the first time show that SLAM expression is correlated with dysregulation of type 1 and type 2 cytokine production in human pathology.

Acute Disease↗
PubMed2005

Life- cycle assessment in pesticide product development: methods and case study on two plant-growth regulators from different product generations.

Environmental assessments in pesticide product development are generally restricted to plant uptake and emissions of active ingredients. Life-cycle assessment (LCA) enables a more comprehensive evaluation by additionally assessing the impacts of pesticide production and application (e.g. tractor operations). The use of LCA in the product development of pesticides, in addition to the methods commonly applied, is therefore advisable. In this paper a procedure for conducting LCA in early phases of product development is proposed. In a case study, two plant-growth regulators from different product generations were compared regarding their application in intensive production of winter wheat. The results showed thatthe reduced emissions from active ingredients of the newer pesticide were compensated by higher impacts from the production process. The authors draw the conclusion that it is important to consider environmental objectives in the procurement of precursors, in addition to the classical goals of increasing the efficacy and reducing the nontarget effects of pesticides. Moreover, the case study showed that decisions based on uncertain results in early stages of product development may need to be revised in later stages, e.g. based on investigations of pesticides' effects on crop yield.

Chlormequat↗
PubMed1995

PDGF and TGF-beta mediate collagen production by mesangial cells exposed to advanced glycosylation end products.

Deposition of type III collagen protein is increased when cultured rat mesangial cells are cultured in media containing high glucose concentrations. Possible mechanisms for this effect include the production of growth factors, such as PDGF and TGF-beta, and the formation of abnormal glucose-protein adducts called advanced glycosylation end products (AGEs). In our studies, neutralizing antibodies to PDGF and TGF-beta prevented increased type III collagen deposition by mesangial cells exposed either to high glucose media or to low glucose media containing AGEs. Daily addition of PDGF or TGF-beta stimulated type III collagen production. However, while co-incubation with the TGF-beta Ab prevented PDGF-stimulated type III collagen production, the PDGF Ab did not prevent TGF-beta-stimulated type III collagen production. Daily addition of PDGF or TGF-beta stimulated, while AGEs inhibited, mesangial cell proliferation after 96 hours. We propose that high extracellular glucose and AGEs stimulate type III collagen production by pathways that involve the intermediate formation of PDGF and TGF-beta by mesangial cells. PDGF may increase type III collagen production by stimulating the intermediate production of TGF-beta. Exposure to high glucose, AGEs, or TGF-beta also leads to impaired mesangial cell proliferation. The autocrine effects of TGF-beta and PDGF play important roles in the effects of high extracellular glucose and AGEs on cultured mesangial cells.

Analysis of Variance↗
PubMed1997

Shift from a dairy product-rich to a dairy product-free diet: influence on cytotoxicity and genotoxicity of fecal water--potential risk factors for colon cancer.

Several epidemiologic studies have suggested that dairy product intake is associated with a decreased incidence of colon cancer. To determine whether the cytotoxicity and genotoxicity of the aqueous portion of human stool (two potential risk markers for the disease) were affected by a change in dairy product intake, 18 healthy male and female volunteers were randomly divided into two groups. In a crossover design, the volunteers shifted from their normal dairy product-rich diet to a dairy product-free diet. Nutritional analysis of the food consumed during the study period showed a significant decrease in energy intake from 9000 to 7866 kJ/d because of a decreased intake of protein and fat. Carbohydrate and fiber intakes remained unchanged during the intervention. Calcium intake decreased significantly from 1488 to 372 mg/d, with similar significant decreases in phosphate and vitamin D intakes. Cytotoxicity of fecal water, analyzed by the HT-29 cytotoxicity assay, indicated a significant decrease in cell survival from 34% to 20% when dairy products were excluded from the participants' diets. Single-cell gel electrophoresis (COMET assay), used to analyze genotoxicity of fecal waters, indicated no differences brought about by the dietary intervention. In conclusion, our findings indicate that a shift from a dairy product-rich to a dairy product-free diet resulted in a significant effect on an accepted risk marker for colon cancer and may suggest that the mechanism by which dairy products are protective is at the level of tumor promotion rather than initiation.

Adult↗
PubMedDate not supplied

A study of the nonprescription drug consumer's understanding of the ranitidine product label and actual product usage patterns in the treatment of episodic heartburn.

INTRODUCTION: A study of the consumer's understanding of the product label instructions and the resulting product use were conducted to support the switch of a product from prescription to nonprescription status. H2 receptor antagonists have recently been approved for nonprescription use. This study evaluated the consumer's understanding of the product label for ranitidine hydrochloride (Zantac 75) and the product usage pattern in the treatment of episodic heartburn. OBJECTIVES: Our objectives were to evaluate each aspect of the communication of labeled indications, contraindications, and directions for use of two label formats (old and new) for a new nonprescription preparation of ranitidine (Zantac) and to evaluate nonprescription consumers' use of ranitidine 75-mg tablets (as Zantac 75) in a medically unsupervised, at-home setting to observe whether these consumers used the product appropriately and followed directions as written on the package label. METHODS: Adult male and female consumers (n = 1405) in a shopping mall environment who were attracted to a poster asking, "Do you have stomach problems?" were recruited for the label comprehension phase (two different label formats) and the 3-week usage phase if after reading the Zantac 75 package label they decided the product was appropriate for them. No instructions regarding the use of Zantac 75 were provided beyond what was printed on the package label. Subjects recorded use in a diary and tablet counts were performed at the end of the study period. A medical history was also taken at this time and an assessment of product use was performed by a physician. RESULTS: In at least 84% of all subjects, both formats were effective in the communication of label objectives for the contraindication against concurrent prescription stomach ulcer medication, maximum daily dose, and maximum duration of dosing at maximum daily doses. The direction to take one tablet per dose was adhered to by 90% of consumers, and 90% of consumers followed the instructions to take no more than two tablets in 24 hours. Ninety-six percent of consumers complied with the direction not to take the maximum daily dose for more than 14 consecutive days. Notably, the maximum daily dose was taken for < or =3 consecutive days by 79% of consumers. The most frequently reported adverse events were headache, acute nasopharyngitis, upper respiratory tract infection, diarrhea, nausea, and menstrual cramps. CONCLUSION: The study demonstrated that the vast majority of a large sample of unsupervised consumers understood the package label and fully complied with the package directions by not exceeding the maximum daily dosage and length of use. Nonprescription consumers safely used Zantac 75 without medical supervision.

Adult↗
PubMed2002

Production of penicillin by fungi growing on food products: identification of a complete penicillin gene cluster in Penicillium griseofulvum and a truncated cluster in Penicillium verrucosum.

Mycobiota growing on food is often beneficial for the ripening and development of the specific flavor characteristics of the product, but it can also be harmful due to the production of undesirable compounds such as mycotoxins or antibiotics. Some of the fungi most frequently isolated from fermented and cured meat products such as Penicillium chrysogenum and Penicillium nalgiovense are known penicillin producers; the latter has been shown to be able to produce penicillin when growing on the surface of meat products and secrete it to the medium. The presence of penicillin in food must be avoided, since it can lead to allergic reactions and the arising of penicillin resistance in human-pathogenic bacteria. In this article we describe a study of the penicillin production ability among fungi of the genus Penicillium that are used as starters for cheese and meat products or that are frequently isolated from food products. Penicillium griseofulvum was found to be a new penicillin producer and to have a penicillin gene cluster similar to that of Penicillium chrysogenum. No other species among the studied fungi were found to produce penicillin or to possess the penicillin biosynthetic genes, except P. verrucosum, which contains the pcbAB gene (as shown by hybridization and PCR cloning of fragments of the gene) but lacks pcbC and penDE. Antibacterial activities due to the production of secondary metabolites other than penicillin were observed in some fungi.

Acyltransferases↗
PubMed2004

Risk assessment strategies for Europe: integrated safety strategy or final product control: Example of Listeria monocytogenes in processed products from pork meat industry.

The European regulation 2160/2003 of November 17th, 2003 clearly shows the European strategy of zoonosis monitoring and control as an integrated approach, including the entire food production chain with a first application to Salmonella control in different animal species. This regulation is the consequence of a risk assessment performed with a "farm to fork" philosophy. European strategy is scarcely different from the American strategy, despite the fact that both were achieved by a quantitative risk assessment, as for instance, in the USA the control of Salmonella in eggs is supposed to be completed by refrigeration. Nevertheless, the EU will still have a final product control approach towards future regulations on microbiological criteria for foodstuffs. The final production monitoring and control with HACCP (93/43/EC) and microbiological criteria is the only one available for L. monocytogenes in foodstuffs. The purpose of this paper is to discuss alternative control strategies for L. monocytogenes in pig production including integrated risk assessment. In France, most of the food-borne outbreaks associated with L. monocytogenes in delicatessen were due to one particular group of strains belonging to serovar 4b and presenting a particular RFLP/PFGE (Restriction Fragment Length Polymorphism/Pulsed Field Gel Electrophoresis) profile. The outbreak itself is always associated with the initial contamination of a RTE ("ready to eat") product and re-contamination by inappropriate handling after cooking. Consequently, in most cases the RTE product is subject to inadequate refrigeration during an excessive shelf-life. The responsibility of the food industry and the consumer is clearly engaged during this scenario of foodborne diseases. The question is how to avoid the introduction of this particular strain of L. monocytogenes in the food chain. In a study we tried to evaluate the risk of pig carcass contamination at slaughterhouse level and to identify the main risk factors associated with the infection of live pigs. In most cases inappropriate cleaning and disinfection of surfaces were associated with the contamination of raw meat, but in some cases the introduction of epidemic strains in the food chain was also associated with primary production. Feeding with soup in piggeries seemed to select a particular microbial ecology associated to L. monocytogenes contamination of live pigs. The possible strategies that may be used to control L. monocytogenes in live pig production are not yet developed sufficiently to be included in the EC regulation but should be discussed in more detail.

Animals↗
PubMed1985

[Production of enterotoxins A, B and C in staphylococcal strains isolated from animal food products and other sources].

Studies were carried out on the production of enterotoxins A, B, and C by a total of 654 strains of Staphylococcus aureus. Of these, 326 were isolated from food products of animal origin (and had no connection with intoxications); 190 were isolated from personnel working in the food industry; and 138 were isolated from milk animals, containers, and equipment at productional enterprises. Thirty strains of S. epidermidis, isolated from food products and workers were likewise tested for the production of the same enterotoxins. The enterotoxins were obtained by the modified method of Hallander, and their demonstration was performed by a variant technique of the double gel diffusion test after Ouchterlony. It was found that the Staphylococcus aureus strains isolated from food products produced enterotoxins in 12.3 per cent of the cases; was found in 6.1% of the strains, C--in 3.1%, and B--in 2.5%. Types A and C were found simultaneously in 0.6% of the strains. Enterotoxins were found in 16.6% of the strains isolated from workers and in 1.7% of those isolated from the udder of cows. The incidence of toxin production and the relative share of the three types of enterotoxins depended on the origin of staphylococci and their capacity to produce them in amounts that could be demonstrated by the methods employed. Under optimal conditions the amounts varied: for strains that produced type A they ranged from 1 to 20 micrograms/cm3; for those that produced type B they were from 1 up to 100 micrograms/cm3; and for those that produced type C they were from 1 to 40 micrograms/cm3. No production of enterotoxins A, B, and C was established with S. epidermidis strains.

Animals↗
PubMed1999

Lipid A directly inhibits IL-4 production by murine Th2 cells but does not inhibit IFN-gamma production by Th1 cells.

Lipopolysaccharide (LPS) is known to be an immunopotentiator but its effect on cytokine production by Th1 and Th2 cells is unknown. We found that high amounts of LPS, its lipid A moiety, and a lipid A analog all induced a decrease in IL-4 production and an increase in IFN-gamma production when given to keyhole limpet hemocyanin (KLH)-restimulated lymph node cells prepared from KLH-primed mice. Lipid A was similarly found to inhibit IL-4 production by purified CD4+ T cells and Th2 clones activated with immobilized anti-CD3epsilon and anti-CD28 antibodies, suggesting that the inhibition is not indirectly mediated through effects on antigen-presenting cells. No inhibitory effect of lipid A was observed on IFN-gamma production by a Th1 clone. Production of both IL-4 by the Th2 clones and IFN-gamma by the Th1 clone were inhibited by the immunosuppressive agent cyclosporin A. These findings indicate that lipid A can directly inhibit IL-4 production by CD4+ T cells without inhibiting the production of IFN-gamma. Lipid A may therefore become a useful tool to study the intracellular events that differentiate Th1 and Th2 cells.

Animals↗
PubMed1988

Expression of c-myc oncogene product and ras family oncogene products in various human malignant lymphomas defined by immunohistochemical techniques.

The authors studied the expression of c-myc and ras family oncogene products in 43 cases of malignant lymphoma (ML) using the immunoperoxidase method. Unfixed frozen sections of lymph nodes from four patients with Hodgkin's disease and 39 with non-Hodgkin's lymphoma, together with normal lymph nodes, were studied by the avidin-biotin-peroxidase complex (ABC) technique. Two monoclonal antibodies, MYC-2 raised against recombinant human c-myc protein (reacting specifically with the c-myc products P62 and P67) and RASK-4 (raised against recombinant P21 and reacting specifically with ras-family product P21) were used. The c-myc product was detected in nuclei of ML cells and some normal, mainly germinal center, lymphocytes. When the staining intensity shown by normal germinal-center lymphocytes was graded as positive (+) or weakly positive (+/-), a very intensely positive reaction ( to ++) was observed in 37 cases (86%) of ML, a positive reaction (+) in four cases (9.3%), and a weakly positive reaction (+/-) in two cases (4.7%). The ras family oncogene product reaction was intensely positive (++) in two cases (4.7%), positive (+) in 16 cases (37.2%), weakly positive (+/-) in 13 cases (30.2%), and negative in 12 cases (27.9%). Western blot analysis confirmed an elevated level of c-myc products in two cases, which showed intense MYC-2 staining, and of ras family products in one case, which demonstrated intense RASK-4 staining. The enhanced expression of these gene products may play an important role in lymphomagenesis of such cases.

Antibodies, Monoclonal↗
PubMed1998

Impaired production of IL-12 in system lupus erythematosus. II: IL-12 production in vitro is correlated negatively with serum IL-10, positively with serum IFN-gamma and negatively with disease activity in SLE.

Interleukin 12 (IL-12) is a key cytokine in regulating type 1 or type 2 cytokine production and in determining the nature of immune responses. Our previous studies demonstrated that its production was significantly impaired in systemic lupus erythematosus (SLE) patients and this deficient IL-12 production was mainly mediated by excessive endogenous IL-10. The present study was designed to further reveal the relationships of in vitro IL-12 production with abnormalities of in vivo cytokine synthesis and disease activity in SLE. Experimental results showed that IL-12 production in vitro was inversely correlated with serum IL-10 level, anti-ds DNA antibody level and SLE disease activity index (DAI), but positively correlated with serum interferon gamma (IFN-gamma) level, with which serum IL-10 correlated negatively. Data also showed that serum IL-10 was significantly higher than that of controls and closely correlated with anti-ds DNA antibody level and SLEDAI. The study confirms that deficient IL-12 production in SLE patients is associated with in vivo abnormalities of cytokine production, especially with increased IL-10 production.

Adult↗
PubMedDate not supplied

Regulatory status of medicinal products for human beings in the European Union. The role of generic products.

In this paper the definition and classification of medicinal products are discussed. Medicinal products from a regulatory and administrative point of view can be classified as: proprietary medicinal products (copy and new drugs), other medicinal products of industrial origin and, magistral and officinal formulas prepared by pharmacies (also called 'generic products'). The term 'generic product' becomes relevant only when the economic impact of medicinal products is considered. The formal characteristics of medicaments, as well as the different possible producers (industry or pharmacy) will be considered also in relation to the interchangeability of medicaments and the role of generic products.

Drugs, Generic↗