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Triamcinolone stimulates bFGF production and inhibits TGF-beta1 production by human dermal fibroblasts.

BACKGROUND: Triamcinolone acetonide has been shown to decrease both cellular proliferation and collagen production by dermal fibroblasts. An alteration of cytokine levels may mediate these effects. OBJECTIVE: To delineate the effect of triamcinolone acetonide on both cellular proliferation and the production of basic fibroblast growth factor (bFGF) and transforming growth factor beta1 (TGF-beta1) by human fibroblasts grown in a serum-free in vitro model. METHODS: Human normal and keloid dermal fibroblasts were propagated in a serum-free in vitro model with exposure to 0, 5, 10, or 20 microm triamcinolone acetonide for 0, 24, 72, or 96 hours. Cell counts were determined by phase contrast microscopy. Levels of bFGF and TGF-beta1 in the supernatants were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: In our study, 20 microm triamcinolone acetonide caused statistically significant increases in the peak levels of bFGF for normal and keloid fibroblast cell lines (P < 0.05). It also caused statistically significant decreases in the level of TGF-beta1 for normal and keloid fibroblast cell lines. For the keloid fibroblasts, 10 microm triamcinolone acetonide also caused a statistically significant decrease in the level of TGF-beta1. CONCLUSION: We conclude from these results that triamcinolone acetonide increases the production of bFGF and decreases production of TGF-beta1 by human dermal fibroblasts.

Analysis of Variance↗

Covalent modification of the glnG product, NRI, by the glnL product, NRII, regulates the transcription of the glnALG operon in Escherichia coli.

Transcription from nitrogen-regulated promoters, such as glnAp2, requires the glnG gene product, NRI, as well as the rpoN(glnF) gene product, sigma60, and is regulated by the glnL gene product, NRII. We find that in a reaction mixture containing NRI, NRII, and ATP, NRII catalyzes the transfer of the gamma phosphate of ATP to NRI. This covalent modification of NRI occurs concurrently with the acquisition of the ability by the reaction mixture to activate transcription from glnAp2. In the presence of PII, the product of glnB, NRII catalyzes the removal of the phosphate from NRI-phosphate. This reaction occurs concurrently with the loss by the reaction mixture of the ability to activate transcription from glnAp2. On the basis of this evidence, we propose that NRI-phosphate activates transcription from nitrogen-regulated promoters and that the role of NRII is control of the formation and breakdown of NRI-phosphate in response to cellular signals of nitrogen availability.

Escherichia coli↗

In differentiated CD4+ T cells, interleukin 4 production is cytokine-autonomous, whereas interferon gamma production is cytokine-dependent.

CD4+ T cells from T cell receptor transgenic mice that have been vigorously primed to be interleukin (IL)-4 producers (T(H2) cells) are capable of producing IL-4 even if restimulated in the absence of IL-4 and in the presence of IL-12. T cells vigorously primed in the absence of IL-4 (T(H1) cells) fail to produce IL-4 even if restimulated under conditions that would cause a naive T cell to produce IL-4. In contrast, interferon gamma (IFN-gamma) production is highly cytokine-regulated. T cells primed in the presence of IL-4 develop into IFN-gamma producers if IFN-gamma is included in the priming culture and if the cells are challenged in the presence of IL-12, presumably reflecting the role of IFN-gamma in inducing responsiveness to IL-12. Cells primed in the absence of IL-4 become highly responsive to IL-12 if IFN-gamma is included in the priming culture, and these cells are excellent IFN-gamma producers upon challenge; IL-12 considerably enhances their production of IFN-gamma. If cells are primed in the absence of IL-4 and IFN-gamma, they show very weak responsiveness to IL-12 as determined by STAT-4 activation. However, these cells acquire IL-12 responsiveness if cultured with IFN-gamma for a period as short as 4 hr. Thereafter, they produce large amounts of IFN-gamma upon challenge with antigen in the presence of IL-12. These results indicate that in primed CD4+ T cells, IL-4 production is largely cytokine-autonomous, whereas IFN-gamma production is highly cytokine-regulated.

Animals↗

Interleukin 18 together with interleukin 12 inhibits IgE production by induction of interferon-gamma production from activated B cells.

Interleukin 18 (IL-18), originally called interferon (IFN)-gamma-inducing factor, is a recently cloned cytokine of approximately 18 kDa synthesized by Kupffer cells and activated macrophages. The major activity associated with this molecule is the induction of IFN-gamma production from anti-CD3-activated T helper 1 cells in the presence of IL-12. B cells produce IgG1 and IgE when stimulated with anti-CD40 and IL-4. Here we show that a combination of IL-12 and IL-18 induces anti-CD40-activated B cells to produce IFN-gamma, which inhibits IL-4-dependent IgE and IgG1 production and enhances IgG2a production without inhibiting the B cell proliferative response. We also show that 24.3% of B cells became positive for cytoplasmic IFN-gamma after being stimulated with IL-12 and IL-18. Furthermore, we show that, like splenic T cells stimulated with anti-CD3, IL-12, and IL-18, B cells produced high level of IFN-gamma in response to anti-CD40, IL-12, and IL-18. Injection of a mixture of IL-12 and IL-18 into mice inoculated with Nippostrongylus brasiliensis or injected with anti-IgD induced IFN-gamma-producing cells that inhibit IgE production in them. Furthermore, B cells obtained from normal mice could develop into IFN-gamma-producing cells in IFN-gamma(-/-) host mice in response to in vivo treatment with IL-12 and IL-18. These results indicate that IFN-gamma from activated B cells differentially regulates IgG1/IgE and IgG2a responses in vitro and in vivo, indicating that B cells act as regulatory cells in the immune response. Present results suggested that injection of IL-12 and IL-18 could present a unique approach for the treatment of allergic disorders.

Animals↗

Use of artificial neural networks to estimate production variables of broilers breeders in the production phase.

1. Although the poultry industry uses state-of-the-art equipment and up-to-date services, in Brazil it generally makes decisions involving all its production variables based on purely subjective criteria. This paper reports the use of artificial neural networks to estimate performance in production birds belonging to a South Brazilian poultry farm. 2. Recorded data from 22 broiler production breeder flocks were obtained, from April, 1998 to December, 1999, which corresponded to 689 data lines of weekly recordings. 3. These data were processed by artificial neural networks using the software NeuroShell 2 version 4.0 (Ward Systems Group). The artificial neural network models generated were compared and selected based on their largest determination coefficient (R2), lowest Mean Squared Error (MSE), as well as on a uniform scatter in the residual plots. The authors conclude that it is possible to explain the performance variables of production birds, with the use of artificial neural networks. 4. The method allows the decisions made by the technical staff to be based on objective, scientific criteria, allows simulations of the consequences related to these decisions, and reports the contribution of each variable to the variables under study.

Animal Feed↗

Inbreeding and inbreeding depression on reproduction and production traits of White Leghorn lines selected for egg production traits.

1. The rate of inbreeding and its effect on reproduction and egg production traits were studied in White Leghorn lines selected for egg production traits. The experiment was carried out for 10 generations in a control line (C) and in lines selected for increased egg number (EN), egg weight (EW) and egg mass (EM). 2. Data were available on reproduction traits, such as percent fertile eggs (PF), percent hatched of fertile eggs (PHF) and percent hatched of total eggs set (PHT), and on egg production traits such as age at 1st egg (AFE), egg number and egg weight. 3. The rate of increase in average inbreeding per generation was 1.50, 1.24, 1.14 and 0.18% for the line EN, EW, EM and C, respectively. The effect of inbreeding on reproduction and production traits was estimated by including the inbreeding coefficient of the hen (Fh), embryo (Fe) and mate (Fs) as a partial linear regression in the model. 4. There was a significant effect of inbreeding on reproduction traits in line EW attributable to the inbreeding of the hen, embryo and mate. No such effect was observed in the other lines. 5. In all lines inbreeding tended to reduce egg number and delay sexual maturity. In general, all lines reacted differently to inbreeding.

Animals↗

Studies on the coupling product between oxidation products derived from pentachlorophenol and cyclodextrins.

The coupling products (CPs), which were formed via the peroxosulfate catalyzed oxidation of pentachlorophenol (PCP) with iron(III)-tetrakis(sulfonatophenyl)porphyrin (Fe(III)-TPPS) in the presence of hydroxypropyl-beta -cyclodextrin (HP-beta -CD) or HP-gamma -CD, were separated by ultrafiltration from the reaction mixture. When the percentages of chlorine species in the reaction mixture were calculated from the concentrations of organic chlorine in the reaction mixture and CPs, 10-25% of chlorine species in the reaction mixture was organic chlorine that was incorporated into CDs. Analyses of the CPs by pyrolysis-GC/MS (Py-GC/MS) and 13C NMR showed that the PCP-derived products were covalently incorporated into the CDs. To evaluate the acute toxicity of the CPs, a Microtox test was examined. Toxicities of the CPs were reduced slightly, compared to the controls (PCP alone and PCP + reaction blanks). In the reaction blanks, mesaconic acid (MA) moieties were detected as a result of the oxidation of CDs in the absence of PCP. Thus, factors in the toxicities, detected in the CPs, can be attributed to the oxidation products derived from CDs, such as MA, as well as the PCP-derived products incorporated into the CDs.

Catalysis↗

A systematic procedure for modeling usability based on product design variables: a case study in audiovisual consumer electronic products.

A systematic modeling approach to describing, prescribing, and predicting usability of a product has been presented. Given the evaluation results of the usability dimension (UD) and the measurement of the product's design variables, referred to as the human interface elements (HIEs), the approach enables one to systematically assess the relationship between the UD and HIEs. The assessed relationship is called a usability model. Once built, such a usability model can relate, in a quantitative manner, the HIEs directly to the UDs, and thus can serve as an effective aid to designers by evaluating and predicting the usability of an existing or hypothetical product. A usability model for elegance of audiovisual consumer electronic products has been demonstrated.

Audiovisual Aids↗

[Rumen fermentation with special reference to volatile fatty acid production during reproduction. 1. Methods and results of volatile fatty acid levels and production rates in vitro].

The target of the investigations was to register part of the synthesis performance in the rumen of ewes during the complete reproduction cycle. With the help of in-vitro experiments with artificial rumen the concentration and production rates of volatile fatty acids in the rumen fluid were measured. From the experiments the measured data of fertility-accentuated crossbreeding (experiment 1) and crossbreeding (experiment 2) ewes were contrasted. The average concentrations of volatile fatty acids in ewes are 95.4 m mol/l in experiment 1 and 109.2 m mol/l in experiment 2 during the early stage gestation, 121.4 m mol/l in experiment 1 and 99.8 m mol/l in experiment 2 in the last stage stage of gestation, 129.6 m mol/l in experiment 1 and 112.8 m mol/l in experiment 2 during lactation and 106.6 m mol/l in experiment 1 and 112.9 m mol/l in experiment 2 during the dry period. The production rates of volatile fatty acids calculated form their concentration amount to 4.8 m mol/l X h in experiment 1 and 2.6 m mol/l X h in experiment 2 in the early stage of gestation, 3.5 m mol/l X h in experiment 1 and 3.1 m mol/l X h in experiment 2 in the last stage of gestation, 3.2 m mol/l X h in experiment 1 and 2.7 m mol/l X h in experiment 2 during lactation and 3.7 m mol/l X h in experiment 1 and 2.9 m mol/l X h in experiment 2 in the dry period. The correlation between the concentration and the production rate of volatile fatty acids is not significantly negative in either of the ewe experiments. The scattering of the individual values is wide so that the individual influence of the test animals as well as the influence of the in-vitro method used permit the conclusion that a significant statement on the influence of the genotype and the stage of reproduction on the production rates cannot be made.

Animals↗

[Studies on rumen fermentation with special reference to the volatile fatty acid production rate in ewes during reproduction. 2. Production rate of volatile fatty acids and rumen volume].

Methods and results of the measuring of the rumen volume and the passage rate as well as the dependence of the production of volatile fatty acids on the parameters mentioned are described. The correlative relations between rumen volume on the one hand and feed passage on the other hand to the production quotas are investigated. Passage rates and rumen volumes were determined with the help of the isotope dilution method. In the course of reproduction rumen volumes of 7.81, 6.41, 8.91, 7.11 in experiment 1 and 5.41, 5.81, 9.51 and 4.71 in experiment 2 were measured in the sequence early stage of gestation, late stage of gestation, lactation and the period between pregnancies. The average total production of volatile fatty acids within 12 hours amounted to 475 mmol, 265 mmol, 313 mmol and 351 mmol in experiment 1 and 155 mmol, 175 mmol, 271 mmol and 144 mmol in experiment 2 in the same sequence. The average passage duration of the feed through the digestive tract of the ewes was 32.4 h in experiment 1 and 33.6 h in experiment 2. The relatively high feed intake of the ewes resulted in a short passage duration and could be a cause of the low production quotas of the volatile fatty acids.

Animals↗

[Energy metabolism of growing broiler chickens kept in groups in relation to the environmental temperature. 2. Heat production, thermoregulatory heat production and thermoneutral temperature (short term measurement)].

In 5 experiments the weekly rhythm of the heat production of growing young broiler chickens kept in groups between their 5th and 57th days of life was measured according to the method of short-time measuring (30-minute measuring periods) in dependence on environmental temperature (ET) between 40 and 5 degrees C in stages of 5 K by means of gas exchange and indirect calorimetry. The keeping temperature ranged from one experiment to the other from 35, 30, 25, 20 to 15 degrees C. The dependence of heat production on ET is parabolic in the medium and high ranges of temperature. As a rule, heat production increases progressively with very low ET. Thermoneutral temperature depends on both, the age (live weight) of the chickens and environmental temperature. Thermoregulatory heat production decreases with growing age. It changed from 24 kJ/kg LW0.75.d.K at the beginning to 8 kJ/kg LW0.75.d.K at the end of the experiments.

Age Factors↗

Long-term egg production and heterosis in quail lines after within-line or reciprocal recurrent selection for high early egg production.

1. Four Japanese quail lines were developed using 13 generations of reciprocal recurrent (lines AA and BB) or within-line selection (lines DD and EE) for high egg number until 98 d of age. In these lines and their reciprocal crosses, egg production, egg weight and mortality were monitored for up to 21 months to evaluate the impact of selection method and line origin on long-term production and heterosis. 2. Both hen-housed total egg number (EN) and hen-day egg laying rate (ELR) were consistently lower in recurrent lines than in lines under within-line selection: after 13 months of test, the difference was -47.1 eggs for EN and -20% for ELR%, whereas mortality was similar at around 20%. 3. Line EE was the best pure line for early egg production (55.2 eggs at 98 d of age) and also gave eggs which were consistently about 2 g larger than those from line DD but it had the highest overall mortality (78.5%) of all lines. On average, line DD laid 399 eggs (EN) over the whole experiment, 84 more than Line EE. 4. Crossbreds from the 2 types of pure lines and line DD had similar patterns and rates of egg production during the whole experiment, as indicated by the similarity of the curves adjusted for those lines by using the monomolecular model for EN and the modified compartmental model for ELR. 5. However, heterosis was higher from recurrent selection lines and it increased more with time than did heterosis from within-line selection lines.

Animals↗

Mononuclear phagocytes have the potential for sustained hydroxyl radical production. Use of spin-trapping techniques to investigate mononuclear phagocyte free radical production.

Monocytes lack lactoferrin and have much less myeloperoxidase than neutrophils. They also acquire a potential catalyst for .OH production (tartrate-resistant acid phosphatase) as they differentiate into macrophages. Consequently, the nature of free radicals produced by these cells was examined using the previously developed spin-trapping system. When stimulated with either PMA or OZ neither monocytes nor monocyte-derived macrophages (MDM) exhibited spin trap evidence of .OH formation. Pretreatment with IFN-gamma failed to induce MDM .OH production. When provided with an exogenous Fe+3 catalyst, both stimulated monocytes and MDM, but not PMN, exhibited sustained .OH production, presumably due to the absence of lactoferrin in mononuclear phagocytes. Sustained production of .OH could contribute to the microbicidal activity of mononuclear phagocytes as well as inflammatory tissue damage under in vivo conditions where catalytic Fe+3 may be present.

Free Radicals↗

Interleukin 12 induces stable priming for interferon gamma (IFN-gamma) production during differentiation of human T helper (Th) cells and transient IFN-gamma production in established Th2 cell clones.

Interleukin 12 (IL-12) facilitates the generation of a T helper type 1 (Th1) response, with high interferon gamma (IFN-gamma) production, while inhibiting the generation of IL-4-producing Th2 cells in polyclonal cultures of both human and murine T cells and in vivo in the mouse. In this study, we analyzed the effect of IL-12, present during cloning of human T cells, on the cytokine profile of the clones. The culture system used allows growth of clones from virtually every T cell, and thus excludes the possibility that selection of precommitted Th cell precursors plays a role in determining characteristics of the clones. IL-12 present during the cloning procedures endowed both CD4+ and CD8+ clones with the ability to produce IFN-gamma at levels severalfold higher than those observed in clones generated in the absence of IL-12. This priming was stable because the high levels of IFN-gamma production were maintained when the clones were cultured in the absence of IL-12 for 11 d. The CD4+ and some of the CD8+ clones produced variable amounts of IL-4. Unlike IFN-gamma, IL-4 production was not significantly different in clones generated in the presence or absence of IL-12. These data suggest that IL-12 primes the clone progenitors, inducing their differentiation to high IFN-gamma-producing clones. The suppression of IL-4-producing cells observed in polyclonally generated T cells in vivo and in vitro in the presence of IL-12 is not observed in this clonal model, suggesting that the suppression depends more on positive selection of non-IL-4-producing cells than on differentiation of individual clones. However, antigen-specific established Th2 clones that were unable to produce IFN-gamma with any other inducer did produce IFN-gamma at low but significant levels when stimulated with IL-12 in combination with specific antigen or insoluble anti-CD3 antibodies. This induction of IFN-gamma gene expression was transient, because culture of the established clones with IL-12 for up to 1 wk did not convert them into IFN-gamma producers when stimulated in the absence of IL-12. These results suggest that Th clones respond to IL-12 treatment either with a stable priming for IFN-gamma production or with only a transient low level expression of the IFN-gamma gene, depending on their stage of differentiation.

Animals↗

Stimulatory and inhibitory effects of interleukin (IL)-4 and IL-13 on the production of cytokines by human peripheral blood mononuclear cells: priming for IL-12 and tumor necrosis factor alpha production.

The production of cytokines in monocytes/macrophages is regulated by several different cytokines that have activating or inhibitory effects. Interleukin (IL)-10, IL-4, IL-13, and transforming growth factor (TGF)-beta are usually considered to be the most important macrophage-deactivating factors, with inhibitory effects on cytokine production. Unlike IL-10 and TGF-beta, which appear to act as downmodulators of many phagocytic cell functions, the mode of action of IL-4 and IL-13 is more complex. Addition of IL-4 and IL-13 to peripheral blood mononuclear cell (PBMC) cultures inhibited production of IL-12, tumor necrosis factor (TNF)-alpha, IL-10, and IL-1 beta induced by lipopolysaccharide (LPS) or Staphylococcus aureus added simultaneously with the cytokines. However, pretreatment of PBMC with IL-4 or IL-13 for > or = 20 h enhanced the production of IL-12 and TNF-alpha in response to LPS or S. aureus several fold in these cells; this IL-4-induced priming for the two cytokines was inhibited by anti-IL-4 neutralizing antibodies. IL-4 priming also enhanced the accumulation of IL-12 and TNF-alpha mRNA induced by LPS and S. aureus. The enhanced accumulation of transcripts for the IL-12 p35 and p40 chains by IL-4 priming was reflected in enhanced secretion of both the IL-12 free p40 chain and the p70 heterodimer. These results suggest an unexpected complexity in the regulatory role of IL-4 and IL-13 in immune responses.

Animals↗

Defective production of antibody to herpes simplex virus in neonates: defective production of T helper lymphokine and induction of suppression.

Defective production of antibodies to herpes simplex virus (HSV) and low resistance to HSV infection in neonatal mice could be reconstituted by using macrophages from syngeneic adult mice plus concanavalin A-stimulated supernatants prepared from adult mouse spleen cells or adult human peripheral blood lymphocytes. In each supernatant, interleukin-2 (IL-2) produced by T helper cells (positive for Lyt 1.2 or OKT4) was necessary to provide reconstitution. Supernatants from neonatal mice failed to mediate reconstitution because of an age-dependent absence of production of IL-2. Although supernatants from neonatal human cell cultures contained IL-2, they failed to reconstitute production of antibody to HSV and resistance to HSV infection because of a suppressor of IL-2 activity. Early antibody production and antibody-dependent cellular effector function are important defenses against HSV infection and are critically defective in the neonate.

Animals↗

Ixodid ticks (Acari: Ixodidae) and livestock production: effect of varying acaricide treatments on ticks and productivity in east coast fever-immunized weaner and dairy cattle.

In a pilot trial to evaluate cost-effective methods of acaricide application, east coast fever-immunized weaner and dairy cattle were subjected to varying tick control regimens. All experimental cattle were maintained under the same extensive system of management. Their monthly tick load, packed cell volumes, incidence of blood protozoans, weight changes, and daily milk production were noted. Apart from Rhipicephalus appendiculatus Neumann, other tick species found in the study site were R. pulchellus Gerstacker, Amblyomma gemma Donitz, Boophilus decoloratus Koch, and A. variegatum F. The control group under a weekly regimen of dipping had fewer ticks than each of the other groups for both weaner and dairy cattle. However, the percentage of increase in weight of the weaner cattle was least for the control group. The milk production of none of the groups was significantly different from that of the control group, although profit per animal for groups maintained under a monthly or six-weekly regimen of acaricide use was highest. The age of the experimental dairy cattle was found not to have any effect on their milk production. It is suggested that with successful immunization against east coast fever, both dairy and weaner cattle may be subjected to reduced dipping or spraying, the level of relaxation being dependent on the tick challenge. However, similar studies should be carried out in as many agroecological zones as possible using different breeds of cattle. Information on the level of acaricide residues in livestock products from different farming systems should also be generated. Only then can a definitive recommendation for a change from the present national intensive dipping policy be made.

Animals↗

Megasphaera elsdenii JCM1772T normalizes hyperlactate production in the large intestine of fructooligosaccharide-fed rats by stimulating butyrate production.

Hyperlactate production is related to disorders of the large intestine such as inflammatory bowel diseases. Lactate, an intermediate in hindgut fermentation, is metabolized to SCFA. Megasphaera elsdenii can convert lactate to butyrate, a physiologically important organic acid for the hindgut mucosa. This experiment was conducted to determine whether M. elsdenii normalizes hyperlactate production and stimulates butyrate production in the rat large intestine. Specific pathogen-free Sprague-Dawley male rats (n = 12) were fed a fructooligosaccharide (FOS)-supplemented (100 g/kg), semipurified diet to induce lactate production. Lactate excretion in all rats was >30 mmol/kg fresh feces on d 2 of FOS-feeding. The rats were divided into two groups on the morning of d 4. One group (n = 5) was dosed orally with M. elsdenii JCM1772T (1.3 x 10(13) cells) for 3 d. The other group was treated with a vehicle solution. Fecal lactate was significantly lower in rats administered M. elsdenii than in controls. An increase in fecal butyrate compensated for the decrease in lactate. The number of cecal epithelial cells was greater in rats administered M. elsdenii than in controls. M. elsdenii has the potential to normalize hyperlactate accumulation in the large intestine, and lactate-utilizing butyrate producers may be useful probiotics when hyperlactate fermentation in the large intestine is a problem.

Animals↗