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PubMed1988

Effect of age, gonadectomy and hypophysectomy on mitochondrial hydroxylation of vitamin D3 (cholecalciferol) and of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol in female and male rat liver.

In a previous study we found that liver mitochondrial side-chain hydroxylation of vitamin D3 (cholecalciferol) and of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol was higher in female than in male rats [Saarem & Pedersen (1987) Biochem. J. 247, 73-78]. The present paper describes the effects of age, gonadectomy and hypophysectomy on these activities. The sex difference became manifest above the age of 7 weeks. Ovariectomy and/or injection of oestradiol valerate had no effect on the hydroxylase activities in adult females. Castration increased, and subsequent testosterone treatment decreased, the hydroxylase activities in adult males. Hypophysectomy had no effect in females, but increased the hydroxylase activities in males. Testosterone treatment had no effect in hypophysectomized females or males. Injection of oestradiol valerate had no effect on the hydroxylase activities in hypophysectomized females. In hypophysectomized males this treatment had no effect on the vitamin D3 25-hydroxylase activity, but decreased the C27-steroid 27-hydroxylase activity in males. Microsomal 1 alpha-hydroxyvitamin D3 25-hydroxylase activity was lower in females than in males in all age groups. Castration or hypophysectomy decreased the activity in male rats. It is concluded that, in adult female rats, the mitochondrial side-chain hydroxylation of vitamin D3 and of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol is independent of sex hormones. In males these activities are regulated by influence of sex hormones on the hypophysis, probably by the presence of androgens in the neonatal period. Different effects on the two hydroxylases indicate the presence of at least two different cytochromes P-450 in rat liver mitochondria.

Aging↗
PubMed1997

Topical glucocorticoid augments IgE-mediated passive cutaneous anaphylaxis in Balb/C mice and mast cell deficient WBB6F1 v/v mice.

BACKGROUND: In a last decade, new types of skin manifestations have been recognized in atopic dermatitis especially in Japan. They are frequently observed in adult patients with atopic dermatitis after a long-standing steroid ointment and termed adult type-atopic dermatitis. OBJECTIVE: To clarify whether topical glucocorticoid (GC) modulates cutaneous inflammatory reactions in addition to known anti-inflammatory effect, we have examined the effect of long-term application of topical GC on IgE-mediated murine cutaneous reactions. METHODS: Fifty microlitres of diflucortolone valerate (1 mg/mL), prednisolone valerateacetate (3 mg/mL), or triamcinolone acetonide (1 mg/mL) were applied seven times on alternate day, to the flank skin of mice. On day 12 when mice received the seventh application of GC, each mouse was given an intravenous application of IgE anti-DNP antibody (PCA titre > x 2560) 1 h before the skin test with 0.15% DNFB in acetone:olive oil (4:1) on the right pinna. The left pinna was painted with a vehicle as a control. Increased ear thickness was measured at 1, 4, 24, 48 and 72 h to assess the augmentry effect of GC. RESULTS: Topical application of GC (50 microg diflucortolone valerate in ethanol) on the flank skin seven times on alternate days, augmented expression of passive cutaneous anaphylaxis reaction on the ear skin induced by intravenous applications of monoclonal IgE anti-DNP antibody and following the challenge test. In contrast, topical application of GC inhibited the reactions when applied on the challenged sites. Several types of GC, but not vitamin D3, augmented the skin reactions and these augmented reactions persisted for 72 h when control skin reactions subsided. GC induced a late phase but not an early phase cutaneous reaction in mast cell deficient WBB6F1 v/v mice by IgE anti-DNP antibody. CONCLUSION: Long-term application of topical GC might modulate local cutaneous immune response and augment IgE-mediated cutaneous reactions. Fc epsilon R(+) cells other than mast cell might be involved in the IgE-mediated late-phase reaction.

Administration, Topical↗
PubMed2000

Microflora-associated characteristics in faeces from allergic and nonallergic infants.

BACKGROUND: The prevalence of allergic diseases has increased particularly over the past 30-40 years. A reduced microbial stimulation during infancy may result in a development of a disturbed balance between Th1- and Th2-like immunity. The gut flora is, quantitatively, the most important source for such stimulation. OBJECTIVE: The aim of the study was to compare the gut microbial flora in 25 allergic and 47 nonallergic 13-month-old infants (range 11-18), through analysing microflora-associated biochemical markers in faeces. METHODS: Microflora associated characteristics (MACs) were assessed by determining the concentrations of eight different short chain fatty acids and the conversion of cholesterol to coprostanol by gas chromatography. Faecal tryptic activity was analysed spectrophotometrically. RESULTS: The allergic infants had lower levels of propionic, i-butyric, butyric, i-valeric and valeric acid. In contrast, they had higher levels of the rarely detected i-caproic acid, which has been associated with the presence of Clostridium difficile. Furthermore, the allergic infants had higher relative distribution of acetic and i-caproic acid. None of the other parameters differed between the groups. CONCLUSION: The results demonstrate differences in the MACs between allergic and nonallergic infants, indicating differences in the composition of the gut flora that may disturb the development of a normal Th1-/Th2-balance in allergic children.

Biomarkers↗
PubMed2003

Parental knowledge of topical therapies in the treatment of childhood atopic dermatitis.

Poor adherence with therapy is a major cause of treatment failure in atopic dermatitis. Reasons given are multifactorial, and include fear of real or imaginary side-effects, under-prescribing, failure to renew prescriptions on time, lack of time, and child refusal of therapy. Most important, however, is lack of knowledge about treatment, in particular the use of topical corticosteroid (TCS) therapy. We conducted a questionnaire-based study to determine the level of use and knowledge of commonly prescribed TCS preparations amongst parents or carers of 100 children attending paediatric outpatient clinics. Weakly potent TCSs were the most commonly used (86%), but poorly understood. Only 35 (41%) who had used hydrocortisone were aware that it was weakly potent, and 44% graded it as moderately potent. Of 65 who had used the moderately potent TCS clobetasone butyrate 0.05% (Eumovate); Glaxo Wellcome, Uxbridge, UK), 19 (29%) graded it as potent and eight (12%) as weak. Of 50 who had used betamethasone valerate 0.1% (Betnovate); Glaxo Wellcome, Uxbridge, UK), 42% did not grade it as potent. Understanding of TCS/antimicrobial combinations was generally worse. The hydrocortisone 1%/fusidic acid 2% combination (Fucidin H(R); Leo, Risborough, Bucks, UK) was graded as moderate or strong by 88% of the 74 who had used it. Over half (53%) of the 34 using the combination of clobetasone butyrate 0.05%/nystatin 100000 i.u./g tetracycline 3% (Trimovate); Glaxo Wellcome, Uxbridge, UK) assumed that it was a potent TCS. Forty-nine had used Fucibet (betamethasone valerate 0.1%, fusidic acid 2%; Leo, Risborough, Bucks, UK) but 34.5% did not grade it as potent. There was poor knowledge of the strengths of some of the most commonly used TCSs, and all steroid/antimicrobial combinations were perceived as being of greater potency than the constituent steroid alone. Fusidic acid was thought to be a steroid by almost half (46.9%) of the respondents. The packaging of the different products by some pharmaceutical companies is remarkably similar and labelling contains information on the compound and percentage rather than potency of the TCS. This may be a source of confusion. We recommend that manufacturers clearly label TCS products by potency as mild, moderate, potent or very potent and that packaging is sufficiently different for each strength of TCS or emollient to avoid confusion. In order to achieve optimal topical treatment for atopic dermatitis, patients and their carers must receive adequate information and training in how and when to use topical therapies in conjunction with written care plans.

Administration, Topical↗
PubMed2003

Insomnia related to postmenopausal syndrome and hormone replacement therapy: sleep laboratory studies on baseline differences between patients and controls and double-blind, placebo-controlled investigations on the effects of a novel estrogen-progestogen combination (Climodien, Lafamme) versus estrogen alone.

Differences in sleep and awakening quality between 51 insomniac postmenopausal syndrome patients and normal controls were evaluated. In a subsequent double-blind, placebo-controlled, comparative, randomized, three-arm trial (Climodien 2/3 = estradiol valerate 2 mg + the progestogen dienogest 3 mg = regimen A, estradiol valerate 2 mg = regimen EV, and placebo = regimen P), the effects of 2 months of hormone replacement therapy were investigated, followed by a 2-month open-label phase in which all patients received Climodien 2/2 (EV 2 mg + dienogest 2 mg = regimen A*). Polysomnography at baseline demonstrated significantly deteriorated sleep initiation and maintenance, increased S1 and decreased S2 in patients. Subjective sleep and awakening quality, well-being, morning drive, wakefulness, memory and reaction time performance were deteriorated too. Treatment with both regimen A and regimen EV induced a moderate, although nonsignificant, improvement in the primary efficacy variable wakefulness during the total sleep period compared with baseline, while under placebo no changes occurred. Secondary efficacy variables concerning sleep initiation and maintenance, and sleep architecture showed similar findings. The apnea and apnea-hypopnea indices improved significantly under regimen A, compared with both baseline and placebo. Subjective sleep and awakening quality improved significantly after regimen A and EV compared with baseline, with the drug-induced changes being superior to those induced by placebo. In the open-label phase, subjective sleep quality improved further, significantly in the former regimen A group. Awakening quality, somatic complaints and morning thymopsyche did not yield any significant findings. Concerning morning noopsychic performance, memory improved significantly after regimen A compared with baseline, fine motor activity after regimen EV. Reaction time performance increased with all three compounds. In conclusion, Climodien significantly improved subjective sleep quality, the apnea and apnea-hypopnea indices of insomniac postmenopausal syndrome patients, while it only marginally improved variables concerning objective sleep and awakening quality.

Aged↗
PubMed2003

Corticosteroid allergy in asthma.

BACKGROUND: Glucocorticosteroids form the basis of therapy for asthma and other allergic diseases. However, they frequently cause delayed contact allergy and occasionally immediate allergy. The purpose of this study was to investigate the occurrence of corticosteroid allergy among patients with asthma and with some complaints caused by inhaled corticosteroids. METHODS: Patch tests with corticosteroids were performed in 51 asthma patients with side-effects from inhalant corticosteroids and in 50 symptom-free asthma patients using the Finn Chamber system. The corticosteroids and their vehicles were: betamethasone-17-valerate 1% in petrolatum, hydrocortisone-17-butyrate (Hc-17-B) 1% in ethanol, tixocortol-21-pivalate 1% in petrolatum, budesonide 0.1% in petrolatum, beclomethasone dipropionate 0.1 and 0.5% in petrolatum and as inhalant powder 200 microg, and fluticasone propionate 0.1 and 0.5% in petrolatum and as inhalant powder 250 microg. The results were read twice, on D4-5 and again on D10. RESULTS: Two patients in the symptomatic group reacted to corticosteroids in patch tests, one to betamethasone-17-valerate, Hc-17-B and budesonide, and the other to budesonide and Hc-17-B. The first patient suffered from widespread eczematous dermatitis when using beclomethasone. Fluticasone caused oropharyngeal irritation, hoarseness and shortness of breath. The second patient experienced a severe rash after the fourth budesonide inhalation. She had used various topical corticosteroids for her atopic dermatitis without any side-effects. None of the symptom-free patients showed positive results. CONCLUSIONS: Delayed allergy to corticosteroids occurs occasionally in asthma, perhaps in the same frequency as in dermatitis. A positive patch test reaction usually means clinical allergy, i.e. the patient cannot use that particular steroid. Cross allergy between corticosteroids is common. However, such patients usually tolerate some other common corticosteroids.

Administration, Inhalation↗
PubMed1995

Relationships between microflora and caecal fermentation in rabbits before and after weaning.

Some microbiological and biochemical parameters of caecal content were studied in 15- to 49-d-old rabbits that were slaughtered sequentially. The ammonia level did not differ before weaning (11.5 mmol/L on average) (P = 0.41) or after weaning (7.4 mmol/L on average) (P = 0.19) but decreased by 40% (P < 0.001) between days 29 and 32. The level of pH decreased linearly (P < 0.001) throughout the period studied. The Escherichia coli counts decreased up to weaning (P < 0.001) and was then not significantly affected by age (P = 0.12). The total volatile fatty acid (VFA) concentration increased between days 15 (8.2 mmol/L) and 25 (33.9 mmol/L) (P < 0.05) and then levelled off below 40 mmol/L. Molar proportions in propionate and in branched-chain fatty acid (BCFA) and valeric acid were high at day 15 but decreased when the animals began to eat solid feed. The C3/C4 ratio reversed at weaning (3.8 on day 15 and 0.5 on day 49) whereas the acetic acid proportion was not affected by age (P = 0.19). High counts of anaerobic microflora were found between 15 and 22 d of age (10(11) bacteria/g of caecal content, on average) and did not change significantly according to the age (at about 10(10) bacteria/g), from day 29 until the end of the experiment (P = 0.29). Amylolytic flora had a similar evolution at a slightly lower level. In contrast, under our breeding conditions cellulolytic microflora slowly colonized the caecum and remained at a low level. The discriminant analysis revealed relationships between ages, intestinal microflora and fermentation parameter; the colibacilli flora was associated with mother-fed animals and amylolytic flora which was linked to BCFA and valeric acid, while the cellulolytic flora was associated with animals older than 4 weeks and linked to the production of C2, C3, C4 and ammonia.

Aging↗
PubMed2003

The lateral spread of epileptiform discharges in rat neocortical slices: effect of focal phencyclidine application.

In vitro and in vivo brain slice techniques were used to examine phencyclidine (PCP) effects on the lateral propagation of epileptiform field potentials (EFP) across adjacent areas of rat frontal neocortex. Epileptiform activity was induced by perfusing slices with Mg 2+-free artificial cerebrospinal fluid. Simultaneous field potential recordings of EFP were obtained from four microelectrodes placed 2-3 mm apart across coronal slices in the third layer. PCP, applied focally between recording sites, blocked rapid propagation across treated areas and resulted in the emergence of spatially separate, independent pacemakers. The characteristics of paroxysmal depolarization shifts did not change significantly by the blockade of lateral propagation of EFP. The same asynchronized pattern of EFP conduction was observed after local application of the N-methyl-D-aspartate (NMDA)-receptor antagonist DL-2-amino-5-phosphono-valeric acid. Local administration of haloperidol as well as NMDA before PCP application reversibly prevented appearance of multiple pacemakers. Focal application of dopamine produced an abnormal pattern of lateral conduction of EFP in 50 % of tested slices. Pacemaker failure as an indicator of functional impairment of cortical integration is the proposed mechanism for developing of schizophrenia-like psychosis associated with epilepsy. Abbreviations. APV: DL-2-amino-5-phosphono-valeric acid EEG:electroencephalogram EFP:epileptiform field potentials NMDA:N-methyl-D-aspartate PCP:phencyclidine SLPE:Schizophrenialike psychosis associated with epilepsy

Animals↗
PubMed2005

Endocrine treatment of male-to-female transsexuals using gonadotropin-releasing hormone agonist.

In transsexual people, cross-sex hormone therapy is an important component of medical treatment. In male-to-female transsexuals, feminizing effects should be achieved before irreversible sex reassignment surgery (SRS) is considered. The most common treatment regimen in male-to-female transsexuals is a combination of ethinyl oestradiol and cyproterone acetate, with the exception of transdermal oestradiol-17beta in individuals over the age of 40. The mortality and morbidity rates with this treatment regimen have been reported in more than 800 patients. Typical side effects include venous thrombosis, elevated liver enzymes, symptomatic gallstones, hyperprolactinaemia and depression. Sixty male-to-female transsexuals were treated with monthly injections of gonadotropin-releasing hormone agonist (GnRHa) and oral oestradiol-17beta valerate for 2 years to achieve feminisation until SRS. There was a significant decline in gonadotropins, total testosterone and calculated free testosterone. In general, the treatment regimen was well accepted. An equal increase in breast size was achieved compared to common hormone therapy. Two side effects were documented. One, venous thrombosis, occurred in a patient with a homozygous MTHFR mutation. One patient was found to be suffering from symptomatic preexisting gallstones. No other complications were documented. Liver enzymes, lipids, and prolactin levels were unchanged. Significantly increased oestradiol and SHBG serum levels were detectable. In addition, an increase in bone mass density, in the femoral neck and lumbar spine, was recorded. We conclude that cross-sex hormone treatment of male-to-female transsexuals using GnRHa and oestradiol-17beta valerate is effective, and side effects and complication rates can be reduced using the treatment regimen presented here.

Adult↗
PubMed1981

Effects induced by two different estrogens on serum individual phospholipids and serum lecithin fatty acid composition.

Eleven oophorectomized women (mean age 34.5 +/- 5.9) received two treatment cycles, one of the 17-C-alkylated ethinyl estradiol 20 microgram per day, and the second of the non-alkylated estrogen, estradiol valerate 2 mg per day for six weeks in separate periods preceded by six weeks without hormonal replacement therapy. Blood samples were drawn before and after six weeks on each estrogen. The samples were assayed for individual phospholipids i.e. cephalin, lecithin, lysolecithin and sphingomyelin after separation of these lipids by thin layer chromatography. The relative fatty acid composition of serum and high density lipoprotein lecithin and serum cholesterol ester was determined by gas liquid chromatography. Both estrogens reversed the symptoms of estrogen deficiency and had similar effects on serum individual phospholipids i.e. causing an increase in lecithin concomitant with a decrease in lysolecithin. It is suggested that this lecithin-lysolecithin shift could depend on an inhibition of the hepatic lipase and its phospholipase A1-activity. Both estrogens increased serum lecithin arachidonic acid without causing any change in linoleic acid (the major essential fatty acid), which indicates that this increase in arachidonic acid could be an estrogenic effect independent of dietary factors. Ethinyl estradiol caused an increase in palmitic and a decrease in stearic acid in the 1-position of serum lecithin while estradiol valerate did not influence these fatty acids at all. This palmitic-stearic acid shift induced by ethinyl estradiol is interpreted as a non-hormonal "drug-effect" linked to the liver toxicity of 17-C-alkylated steroids in spite of the lack of influence on routine liver function tests.

Adult↗
PubMed2002

Human neuropathy target esterase catalyzes hydrolysis of membrane lipids.

A neuronal membrane protein, neuropathy target esterase (NTE), reacts with those organophosphates that initiate a syndrome of axonal degeneration. NTE has homologues in Drosophila and yeast and is detected in vitro by assays with a non-physiological ester substrate, phenyl valerate. We report that NEST, the recombinant esterase domain of NTE (residues 727-1216) purified from bacterial lysates, can catalyze hydrolysis of several naturally occurring membrane-associated lipids. The active site regions of NEST and calcium-independent phospholipase A(2) (iPLA(2)) share sequence similarity, and the phenyl valerate hydrolase activity of NEST is inhibited by low concentrations of iPLA(2) inhibitors. However, on incubation with NEST, fatty acid was liberated only extremely slowly from the sn-2 position of phospholipids (V(max) approximately 0.01 micromol/min/mg and K(m) approximately 0.4 mm for 1-palmitoyl, 2-oleoylphosphatidylcholine). Comparison of the NEST-mediated generation of (14)C-labeled products from two differentially labeled (14)C-phospholipid substrates suggested that a rate-limiting sn-2 cleavage was followed very rapidly by hydrolysis of the resulting lysophospholipid. Among the various naturally occurring lipids tested with NEST, lysophospholipids were by far the most avidly hydrolyzed substrates (V(max) approximately 20 micromol/min/mg and K(m) approximately 0.05 mm for 1-palmitoyl-lysophosphatidylcholine). NEST also catalyzed the hydrolysis of monoacylglycerols, preferring the 1-acyl to the 2-acyl isomer (V(max) approximately 1 micromol/min/mg and K(m) approximately 0.4 mm for 1-palmitoylglycerol). NEST did not catalyze hydrolysis of di- or triacylglycerols or fatty acid amides. This demonstration that membrane lipids are its putative cellular substrates raises the possibility that NTE and its homologues may be involved in intracellular membrane trafficking.

Amino Acid Sequence↗
PubMed2003

Regulation of glucose-6-phosphatase gene expression in cultured hepatocytes and H4IIE cells by short-chain fatty acids: role of hepatic nuclear factor-4alpha.

Mechanisms underlying dietary nutrient regulation of glucose-6-phosphatase (Glc-6-Pase) gene expression are not well understood. Here we investigated the effects of short-chain fatty acids on the expression of this gene in primary cultures of rat hepatocytes and H4IIE hepatoma cells. Propionate, butyrate, valerate, and caproate induced severalfold increases in the expression of Glc-6-Pase mRNA. In reporter gene assays, propionate, valerate, caproate, and also octanoate increased Glc-6-Pase promoter activity by 6-16-fold. Butyrate, by itself, had little or no effect on promoter activity, but it induced a robust increase (45-fold) in promoter activity in cells co-transfected with a plasmid expressing the transcription factor HNF-4alpha (alpha isoforms of hepatic nuclear factor 4). HNF-4alpha also enhanced promoter activity induced by other short-chain fatty acids. A dominant negative form of HNF-4alpha abrogated the fatty acid-induced promoter activity, a finding that accentuates a role for HNF-4alpha in the transcription process studied here. In cells transfected with HNF-4alpha, short-chain fatty acids and trichostatin A, an inhibitor of histone deacetylase, synergistically enhanced promoter activity, suggesting that hyperacetylation of histones is an important component of the transactivation of the Glc-6-Pase gene promoter by HNF-4alpha. Region-751/-466 of this promoter contains seven putative HNF-4alpha-binding motifs. Binding of HNF-4alpha to this region was confirmed by electrophoretic mobility shift and chromatin immunoprecipitation assays, indicating that HNF-4alpha is recruited to the Glc-6-Pase gene promoter during short-chain fatty acid-induced transcription from this promoter.

Amino Acid Motifs↗
PubMed1994

The effect of condensed tannins in Lotus corniculatus on plasma metabolism of methionine, cystine and inorganic sulphate by sheep.

Fresh Lotus corniculatus containing 27 g extractable condensed tannin (CT)/kg dry matter (DM) and 8 g bound CT/kg DM was fed at hourly intervals to sheep held in metabolism cages to study the effects of CT on nutrient digestion and on metabolism of methionine, cystine and inorganic sulphate in plasma. Polyethylene glycol (PEG) was continuously infused into the rumen of half the sheep to remove the effects of CT. Principal measurements in the two groups were plasma irreversible loss (IRL) rate and interconversions of methionine, cystine and inorganic sulphate using 35S labelling. CT in Lotus corniculatus had no effects on the apparent digestion of cellulose and minerals, slightly depressed DM, organic matter and hemicellulose digestion and markedly reduced the apparent digestion of N (P < 0.01). The concentration of NH3 and molar proportions of iso-butyric acid, iso-valeric acid and n-valeric acid in rumen fluid were markedly increased by the PEG infusion (P < 0.01), whereas total volatile fatty acid concentration and molar proportions of acetic acid, propionic acid and n-butyric acid were not affected. PEG infusion temporarily increased rumen protozoa numbers. CT greatly increased the IRL of plasma cystine (13.1 v. 7.0 mumol/min; P < 0.05) and reduced IRL of plasma inorganic sulphate (36.8 v. 48.1 mumol/min; P < 0.01) but had no effect on methionine IRL. CT increased transulphuration of methionine to cystine (4.37 v. 1.24 mumol/min; P < 0.05), increased cystine entering the plasma from whole-body protein turnover plus absorption from the small intestine (9.34 v. 5.75 mumol/min; P < 0.05) and increased cystine flux to body synthetic reactions (11.89 v. 5.41 mumol/min; P < 0.05). CT had no effect on the proportion of methionine total flux transferred to sulphate (0.05 v. 0.06; P < 0.05), reduced the proportion of methionine flux transferred to body synthetic reactions (0.68 v. 0.86) and markedly reduced the proportion of cystine flux transferred to sulphate (0.09 v. 0.27; P < 0.01). It was concluded that CT in Lotus corniculatus reduced rumen protein degradation and markedly increased utilization of plasma cystine for body synthetic reactions.

Animal Feed↗
PubMed2002

Effects of dietary non-digestible oligosaccharides on microbial characteristics of ileal chyme and faeces in weaner pigs.

Fructooligosaccharides (FOS) and transgalactooligosaccharides (TOS), which are non-digestible oligosaccharides (NDO), were included at 10 and 40 g/kg in an NDO--free control diet at the expense of purified cellulose. Each of the 5 diets was fed to 4 weaner pigs and microbial characteristics of their ileal chyme and faeces were assessed. The NDO-pigs had lower ileal pH than the control pigs. Dietary NDO did not affect the ileal volatile fatty acid concentration, though FOS-pigs had a higher concentration of lactic acid and relatively more iso-valeric acid and less acetic acid than TOS-pigs. The NDO-pigs had lower ileal aerobic bacterial counts than the control pigs, whilst the FOS-pigs had a larger ileal anaerobic bacterial counts than the TOS-pigs. The NDO-pigs had an higher faecal pH and their faecal volatile fatty acid pool contained relatively more iso-butyric acid and iso-valeric acid than the control pigs. The TOS-pigs tended to have higher faecal anaerobic bacterial counts and had a smaller concentration of faecal volatile fatty acid than the FOS-pigs. We concluded that whilst effects at the faecal level may have been partly due to a reduced intake of cellulose, dietary NDO can exert precaecal prebiotic effects in weaner pigs.

Animals↗
PubMed2005

Effects of Lactobacilli and lactose on Salmonella typhimurium colonisation and microbial fermentation in the crop of the young turkey.

1. Three experiments were performed to examine the effects of Lactobacilli and lactose on microbial fermentation and Salmonella enterica serovar Typhimurium colonisation in the crop of the young turkey. 2. The following carboxylic acids were detected in the crop ingesta: formic, acetic, butyric, lactic, valeric, caproic, oxalic, phenyl acetic, succinic and fumaric; propionic, isobutyric and isovaleric acids were not detectable. 3. At the beginning of the night, there were considerable quantities of ingesta in the crop of young turkeys. During the scotophase, there were progressive reductions in the contents and pH. Moreover, there were linear increases in the concentration of lactic, valeric and caproic acids (by approximately 7-fold over 8 h). Much smaller changes in crop pH were observed in the study where dietary treatments of Lactobacilli were not included. 4. Chronic addition of lactose or Lactobacilli to the diet exerted modest effects on the carboxylic acid concentration in the crop contents but did not consistently influence colonisation of the crop by Salmonella enterica serovar Typhimurium. 5. Young turkeys confine eating to the hours of illumination (photophase) with a peak in consumption prior to the subjective dusk.

Aging↗
PubMed1995

Colonic protein fermentation and promotion of colon carcinogenesis by thermolyzed casein.

Thermolyzed casein is known to promote the growth of aberrant crypt foci (ACF) and colon cancer when it is fed to rats that have been initiated with azoxymethane. We speculated that the promotion was a consequence of increased colonic protein fermentation (i.e., that the thermolysis of the casein decreases its digestibility, increases the amount of protein reaching the colon, and increases colonic protein fermentation and that the potentially toxic products of this fermentation promote colon carcinogenesis). We found that the thermolysis of casein reduces its digestibility and increases colonic protein fermentation, as assessed by fecal ammonium and urinary phenol, cresol, and indol-3-ol. Thermolysis of two other proteins, soy and egg white protein, also increases colonic protein fermentation with increased fecal ammonia and urinary phenols, and thermolysis of all three proteins increases the levels of ammonia and butyric, valeric, and i-valeric acids in the cecal contents. We found, however, that the increased protein fermentation observed with thermolysis is not associated with promotion of colon carcinogenesis. With casein, the kinetics of protein fermentation with increasing thermolysis time are clearly different from the kinetics of promotion of ACF growth. The formation of the fermentation products was highest when the protein was thermolyzed for one hour, whereas promotion was highest for protein that had been thermolyzed for two or more hours. With soy and egg white, thermolysis increased colonic protein fermentation but did not promote colon carcinogenesis. Thus, although thermolysis of dietary casein increases colonic protein fermentation, products of this fermentation do not appear to be responsible for the promotion of colon carcinogenesis. Indeed, the results suggest that protein fermentation products do not play an important role in colon cancer promotion.

Animals↗
PubMed2003

Synthetic estrogen-mediated activation of ERK 2 intracellular signaling molecule.

Ovarian steroids are important modulators of normal cell growth and differentiation as well as of carcinogenesis. External stimuli trigger cell surface receptors, resulting in activation of central signal transduction pathways, that are mediated by members of the mitogen-activated protein kinase (MAPK) family. These in turn, indirectly regulate cellular functions such as cell proliferation, cell cycle, and maintenance of malignant phenotype. In our in vitro study, we have investigated the effects of two synthetic estrogens on ERK 2 activation. Estrogen receptor positive cells were incubated with the synthetic estrogens, ethinylestradiol (10(-9) mol/l) and 17 beta-estradiol valerate (10(-9) mol/l), epidermal growth factor (EGF) (10 ng/ml) and the natural estrogen 17 beta-estradiol (10(-9) mol/l), for 5 min. The same experiments were repeated prior to preincubation with the antiestrogen ICI 182780. ERK 2 or the active form alone were detected by immunoblotting. A cell proliferation assay was used to study the response of cells to various treatments. Time kinetics were performed to study duration of kinase activated state. Cell incubation with EGF as well as with either natural or synthetic estrogen stimulated proliferation. ICI 182780 inhibited this effect, but only in the case of estrogen. Synthetic estrogens activated MAP kinase in a time-dependent fashion, similar to 17 beta-estradiol. The estrogen receptor antagonist ICI 182780 blocked this effect. EGF induced a more pronounced and prolonged activation, even in the presence of the antiestrogen. Ethinylestradiol as used in oral contraceptives, and 17 beta-estradiol and 17 beta-estradiol valerate as used in hormone replacement therapy, are able to activate MAP kinase. This activation was blocked by an antiestrogen.

Blotting, Western↗
PubMed2005

Effects of combined estrogen/testosterone therapy on bone and body composition in oophorectomized women.

OBJECTIVE: To evaluate the effect of adding testosterone undecanoate 40 mg daily to estrogen therapy on bone markers, bone mineral density and body composition in oophorectomized women. METHODS: Fifty women, 45-60 years old, who had undergone a hysterectomy and bilateral salpingo-oophorectomy for benign disorders, were randomly assigned to oral treatment with testosterone undecanoate 40 mg plus estradiol valerate 2 mg daily or placebo plus estradiol valerate 2 mg daily. Twenty-four weeks later, cross-over was performed to the other treatment regimen. Forty-four women completed the study. Their serum concentrations of insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3, osteocalcin, carboxyterminal telopeptide aminoterminal (ICTP), of type I collagen propeptide of type I procollagen (PICP) and interleukin (IL)-1 receptor antagonist were measured at baseline and after 24 weeks of both treatments, as were also their body mass index (BMI) and blood pressure. Bone mineral density of the total body, spine and hip and total body fat, total lean body mass, trunk fat and trunk lean mass were determined by dual-energy X-ray absorptiometry measurements at baseline and after 24 weeks of both regimens. RESULTS: During treatment, the addition of testosterone counteracted the decrease in IGF-I and PICP seen with estrogen therapy alone. Osteocalcin and ICTP were significantly reduced to the same extent by both therapies. No change ocurred in the IL-1 receptor antagonist. A significant increase was seen in total lean body mass with the estrogen/testosterone regimen, but the total fat mass, trunk lean or fat mass remained unchanged after 24 weeks of both treatments. No effect was detected on total, hip or spinal bone mineral density after treatment with estrogen alone or estrogen/testosterone. Likewise, BMI and blood pressure were unaffected. CONCLUSIONS: The addition of testosterone to oral estrogen might have positive effects on bone as suggested by the fact that it counteracted the decline in IGF-I and PICP levels. An anabolic effect on muscle was reflected by an increase in the total lean body mass. No adverse effects were noted on BMI, fat distribution or blood pressure during the 6-month treatment with oral testosterone undecanoate.

Body Composition↗