Search

Introduction: Infectious diarrhea is still one of the leading causes of losses of newborn calves. Therefore the prophylactic use of probiotics, which are supposed to inhibit the propagation of pathogens through repression from colonization on the gut, seems very promising. So the balance of the intestinal flora is affected in a positive manner. Another way to control infectious diarrhea consists of oral or parenteral application of specific antibodies (origin could be serum, milk, colostrum or chicken eggs) against the most common pathogens. Methods: In a field trial 198 neonate calves (48.5% female 51.5% male) of mainly the breed 'Deutsches Fleckvieh' have been divided according daily treatment into five groups (n = 39/40): I [control]; II [5 g probiotic powder with Bacillus cereus var. toyoi (ToyoCerin) from LAH, Cuxhaven]; III [10 g egg yolk powder containing 200 mg IgY with specific antibodies against rotavirus, coronavirus and Escherichia coli K99 (F5) pilus antigen (modified GLOBIGEN 88) from LAH, Cuxhaven]; IV [10 mL colostrum (SERIMMUN 2000) containing 1 g bovine immunoglobulins with specific antibodies against rotavirus, coronavirus and different Escherichia coli antigens from LAH, Cuxhaven]; V (egg yolk and probiotic powder according to groups II and III). The prophylactic feed additives were given together with the milk from day 2 to day 14 postnatum. In the case of diarrhea the procedure was continued in addition to therapeutic treatments. The effectiveness of the preparations was estimated through clinical examinations including measurements of the body weight gain and determination of serum immunoglobulin concentrations by means of ELISA. Furthermore the presence of infectious agents in feces was proved by Lactovac (Hoechst, UnterschleiBheim) and BioX (Bvd. Edm. Machtens, Bruxelles) ELISA. Results: 62% (123 animals) of the calves showed diarrhoea; in 80% of these pathogens could be found in feces. Among all calves rotavirus infections (31%) predominated coronavirus (7%), Escherichia coli K99 (1%) and cryptosporidia (23%) infections. Relating to frequency of the pathogens and incidence intensity, beginning and duration of diarrhoea there was no statistical significant difference between the groups. But the combined application of probiotic and egg powder or of the probiotic alone reduced tendentially the occurrence of rota- and coronavirus infections and, in the combined group intensity of diarrhea during infections with rotavirus and such with cryptosporidia was lower. Also, the calves of group II and of group V became ill with diarrhea on average I d later than the others and, if pathogen positive, they had a slightly shorter duration of diarrhea. The greatest body weight gain at day 14 showed group V with 7.7 kg (control: 5.8 kg); this parameter was for the pathogen positive animals of group V with diarrhea (6.0 kg) nearly statistically significant in comparison with the corresponding ones in the control group (3.4 kg). Serum concentrations of IgG differed between diarrhea positive (4.4 mg/mL) and negative (5.6 mg/mL) calves without any influence of the group treatments. Conclusion: To ensure the positive effects seen in this trial it will be necessary to further investigate the dosage and the time schedule of application of these feed additives.

Non-mammalian NK cells have not been characterized in detail; however, their analysis is essential for the understanding of the NK cell receptor phylogeny. As a first step towards defining chicken NK cells, several tissues were screened for the presence of NK cells, phenotypically defined as CD8⁺ cells lacking T- or B-lineage specific markers. By this criteria, ¬30% of CD8⁺ intestinal intraepithelial lymphocytes (IEL), but <1% of splenocytes or peripheral blood lymphocytes were defined as NK cells. These CD8⁺CD3^- IEL were used for the generation of the 28-4 mAb, immunoprecipitating a 35-kDa glycoprotein with a 28-kDa protein core. The CD3 and 28-4 mAb were used to separate IEL into CD3⁺ IEL T cells and 28-4⁺ cells, both co-expressing the CD8 antigen. During ontogeny, 28-4⁺ cells were abundant in the IEL and in the embryonic spleen, where two subsets could be distinguished according to their CD8 and c-kit expression. Most importantly, 28-4⁺ IEL lysed NK-sensitive targets, whereas intestinal T cells did not have any spontaneous cytolytic activity. These results define two major, phenotypically and functionally distinct IEL subpopulations, and imply an important role of NK cells in the mucosal immune system.

There is ample evidence that zinc plays an important role in bone metabolism and zinc deficiency has been implicated as a risk factor in the development of osteoporosis. It was the aim of the present study to investigate the skeletal effects of alimentary zinc deficiency in growing rats using quantitative bone histomorphometry. Twenty-four male Sprague Dawley rats with a mean initial body weight of 101±2 g were allocated in two groups of 12 rats each and had free access to a semi-synthetic, casein-based, zinc-deficient diet (0.76 mg zinc/kg) or to the same diet supplemented with 60 mg zinc per kg. All rats were sacrificed 42 days after the start of the experiment and the right distal femur was removed for bone histomorphometry. Relative to controls (+Zn), the zinc-deficient rats (-Zn) had a significantly lower body weight and about an 80% reduction in plasma and femur zinc concentration. The histomorphometric evaluation of the distal femoral metaphysis showed that zinc deficiency led to a 45% reduction (p<0.01) in cancellous bone mass and to a deterioration of trabecular bone architecture, with fewer and thinner trabeculae. The osteopenia in -Zn rats was accompanied by significant reductions in osteoid perimeter (- 31%, p<0.05), osteoblast perimeter (- 30%, p<0.05), and osteoclast number (-38%, p<0.01) relative to +Zn controls. We conclude that zinc deficiency induced low turnover osteopenia in femoral cancellous bone of growing rats. These results support the hypothesis that zinc deficiency during growth may impair the accumulation of maximal bone mass in humans; additionally, they suggest that zinc deficiency may play a role as a risk factor in the pathogenesis of osteoporosis.

Under certain pathological conditions such as cerebral ischemia and reperfusion the occur­rence of free radicals is remarkably increased. However, only very little information is avail­ able on their quantitative relevance for the pathophysiology and final outcome of diseases. The aim of the present study was to evaluate the contribution of oxygen radicals in the pathogenesis of a stroke. For this purpose a rat model for stroke was used. Two of three vitamin E deficient groups were repleted with different dosages of DL-a-tocopherylacetate. N o signs of vitamin E deficiency could be observed. However, the weight gain during reple­tion was increased in the vitamin E repleted groups. Brain infarction was created by occlusion of the right middle cerebral artery (MCAO) for two hours. After 24 hours the measurements of infarct volumes were taken. The infarct volume of the group with the highest repletion dosage was significantly reduced by 81%. This was also expressed in a higher rate of gait disturbances after MCAO of the deficient animals. The control of vitamin E status exhibited a similar repletion-dependent level in plasma and brain. These results strongly support the hypothesis that the generation of oxygen radicals occurring during reperfusion is an impor­tant aspect of the pathophysiological mechanism in brain infarction.

Bei 26 neugeborenen männlichen Kälbern aus 23 verschiedenen Betrieben wurden im Rahmen eines Versuchs zur Prophylaxe von infektiösen Durchfallerkrankungen mit spezifischen Dotterantikörpern auch Untersuchungen zur systemischen Verfügbarkeit von kolostralem bovinen Immunglobulin G (blgG) und von Hühner‐Immunglobulin Y (IgY) aus zugefüttertem Volleipulver durchgeführt. Den Kälbern wurde dazu in den ersten 14 Lebenstagen täglich zum gleichen Zeitpunkt eine Blutprobe entnommen. In Verbindung mit der Kolostrumgabe war die blgG‐Konzentration am Tag 1 post natumam höchsten und lag im Mittel bei einem Wert von 9,3 mg/ml Serum. Der gemittelte blgG‐Spiegel nahm anschließend kontinuierlich ab und erreichte am Tag 12 post natumeinen signifikant niedrigeren Wert von 4,9 mg/ml Serum. Bis zum Ende der Beobachtungsperiode (Tag 14 post natum)blieb die mittlere blgG‐Konzentration weitgehend stabil (5,2 mg/ml). Die Gesamtproteinkonzentrationen im Serum blieben hingegen im Beobachtungszeitraum relativ konstant (im Mittel 56,8 mg/ml; SD 11,2). Die Anzahl der Kolostrumgaben je Tier hatte keinen signifikanten Einfluß auf die Höhe der bIgG‐Konzentrationen. Die Streubreite der individuellen Konzentrationen war an den einzelnen Tagen der ersten beiden Lebenswochen enorm. Der mittlere Variationskoeffizient lag bei 52,1 % (SD 5,7). Bei der Berechnung der individuellen bIgG‐Kurvenverläufe mittels einer Regressionsgleichung ergaben sich zwei Gruppen mit signifikant verschiedenem Eliminationsverhalten. So zeigte eine Gruppe (n= 10) mit Eliminationskonstanten von k < —0,02 eine mittlere Halbwertszeit für blgG von 24,3 Tagen (SD 4,6). Bei den übrigen Kälbern (n = 16) mit einer Eliminationskonstante für blgG von k >—0,02 lag die berechnete Halbwertszeit möglicherweise aufgrund der frühzeitiger erfolgten blgG‐Eigensynthese bei einem theoretischen Wert von 68,5 Tagen (SD 36,7).An 18 Kälbern wurde im selben Versuchszeitraum täglich 20 g Volleipulver mit einem IgY‐Gehalt von 15 mg/g verabreicht. Wurde das Eipulver bereits erstmals in den ersten 12 Lebensstunden zugefüttert, so erreichten die Kälber maximale IgY‐Konzentrationen von im Mittel 1,9 ug/ml Serum. Ein späterer Beginn der Eipulverzulage hatte signifikant niedrigere IgY‐Spiegel zur Folge. Wurde sie beispielsweise zwischen der 25igsten und 48igsten Lebensstunde begonnen, so zeigte sich eine mittlere IgY‐Konzentra‐tion von nur 0,035 μg/ml Serum. Aus der Berechnung der individuellen Eliminationskonstanten mittels einer Regressionsgleichung (r2= 0,84) ergab sich eine mittlere Halbwerfszeit für IgY von 5,0 Tagen (SD 2,5). Um die Resorption und damit auch die mögliche systemische Wirksamkeit von speziesfremden Antikörpern weitgehend zu verhindern, sollte Eipulver zur Prophylaxe von infektiösen Durchfallerkrankungen beim neugeborenen Kalb demzufolge erst 24 bzw. besser 48 Stunden post natumzugefüttert werden. Entscheidend für eine wirksame Prophylaxe gegen infektiöse Durchfallerkrankungen ist allein die hohe intestinale und nicht die systemische Verfügbarkeit von spezifischen Antikörpern.

An sechs ausgewachsenen, mit Pansennstein versehenen Ochsen wurde der Einfluß des Ernährungsniveaus auf die Passage des Verdauungsbreis aus dem Reticulorumen und durch den gesamten Verdauungstrakt untersucht. Die Tiere erhielten eine gemischte Ration, die in der DM im Mittel aus 43 % Grassilage, 25 % Maissilage, 30 % Konzentratfutter und 2 % Mineralfutter bestand und bei drei Ernährungsniveaus vorgelegt wurde: Erhaltungsbedarf und 1,5facher sowie 2facher Erhaltungsbedarf. Gefüttert wurde 2mal täglich, ab 7 Uhr und ab 19 Uhr. Die Versuchsanordnung entsprach einem doppelt besetzten 3×3 lateinischen Quadrat mit Versuchsperioden von 21 Tagen. Zu Beginn jeder Versuchsperiode erhielten die Tiere Einmaldosen der Marker Titan(IV)‐oxid (TiO2) mit dem Konzentratfutter und Cr‐EDTA als unverdünnte Lösung direkt in den Pansen. Kotproben wurden nach der Markergabe rektal über 120 h hinweg entnommen. Passageparameter wurden mit Hilfe unterschiedlicher Schätzverfahren ermittelt, wobei ein monoexponentielles und ein biexponentielles Modell, Modelle mit Gamma‐Zeitabhängigkeit sowie ein Modell, in dem die mittlere Verweildauer des Markers im gesamten Verdauungstrakt als Mittelwert aller Punkte der Marker‐Exkretionskurve berechnet wird, verwendet wurden. Mit steigendem Ernährungsniveau nahm die Passagerate von TiO2aus dem Reticulorumen zu, die mittlere Verweildauer im gesamten Verdauungstrakt nahm ab. Die Ergebnisse der unterschiedlichen Modellansätze stimmten mit wenigen Ausnahmen gut überein. Außerdem zeigte sich eine gute Übereinstimmung zwischen den Ergebnissen der TiO2‐Passage und den Werten, die andere Versuchsansteller für die Passage kleiner, prinzipiell passagefähiger Teilchen bei ähnlichen Rationstypen ermittelten. Auch für Cr‐EDTA nahm die Passagerate aus dem Reticulorumen mit steigendem Ernährungsniveau zu, die mittlere Verweildauer im Reticulorumen und im gesamten Verdauungstrakt nahm ab. Es zeigten sich jedoch Differenzen zwischen den Modellansätzen mit oder ohne Zeitabhängigkeit. Die Anpassung an den Kurvenverlauf der Cr‐EDTA‐Ausscheidung mit dem Kot war bei den Modellen mit Gamma‐Zeitabhängigkeit unbefriedigend. Für beide Marker ergaben alle verwendeten Modelle übereinstimmend eine deutliche Beschleunigung der Passage aus dem Reticulorumen bzw. eine deutliche Verkürzung der Verweildauer im Reticulorumen und im gesamten Verdauungstrakt, wenn das Ernährungsniveau von der Deckung des Erhaltungsbedarfes auf das 1,5fache des Erhaltungsbedarfes angehoben wurde.

Experiments with continuous infusion of [14C] isobutyrate and single injection of [3H] glucose were performed in two sheep under fed and fasted conditions in order to investigate the contribution of isobutyrate to glucose synthesis.The pool size, total entry rate and irreversible loss of glucose in the fed sheep were 2.8 mmol/kg0.75, 1.70 and 1.43 mmol/h per kg0.75. After 72-h fasting these parameters decreased about 40% but recycling of glucose carbon increased from 16 to 38 % of the total entry rate. Isobutyrate infused intravenously at a rate of 3.5 mmol/h contributed to a minimum of 3-5% of glucose entry indicating that at least 40-60 % of the infused isobutyrate was used for net glucose synthesis. The efficiency of the glucogenic and energetic use of isobutyrate as compared to propionate is discussed.

The relation between the ratio of the natural 13C and 12C isotopes of carbon in silages of a C3 species (winter-barley) and a C4 species (maize) was examined as a potential marker in rate of passage studies in ruminants concurrently with the external marker titanium(IV)-oxide (TiO2). Diets were formulated to contain 140 g crude protein kg-1 dry matter. Two ruminally cannulated steers and two wethers were fed on a diet based on whole-plant winter-barley silage (BS) once daily at 07.00 h. The animals received one single meal of whole-plant maize silage (MS), concurrently with a single dose of TiO2. Animals were then switched back to BS for the remainder of the experiment. Faeces were collected over 5 days post MS feeding. Ruminal pH in steers appeared to be unaffected by switches from C3 to C4 silage feeding, and vice-versa. In steers, faecal samples peaked in TiO2 value approximately 22 to 28 h after dosing, and then declined. Carbon isotope values peaked approximately 31 to 35 h after steers received the C4 silage, and then declined. The time of this peak corresponded closely to that from a study which used intrinsically labelled 13C forage. Carbon isotope values from faecal samples of wethers showed no clear peak and decline. However, measurement of carbon isotope ratios in neutral detergent fibre of silage and faeces instead of whole material greatly improved curve shaping. Provided that C3 and C4 forages of similar chemical composition and digestibility are used in order to minimize perturbation of rumen fermentation and subsequent passage processes, naturally occurring differences in stable carbon isotope ratios may be used as passage markers in ruminants. This restriction will limit the potential use of estimating passage rates from naturally occurring differences in carbon isotope ratios to only a few specific cases.

Winter wheat (Triticum aestivumL.), harvested at late milk, early dough, and hard dough stages of maturity was ensiled for nutritive comparisons. Diets were adjusted to 13% CP with a soy protein concentrate and fed to six ruminally fistulated growing steers and nine adult wethers in a repeated 3 × 3 Latin square design to study the effects of maintenance and ad libitum intakes on digestibility of different feed fractions. At both intakes, digestion values for the steers were greater than or equal to those for the sheep for all feed fractions except CP. Wethers achieved greater intake per unit of BW than steers during ad libitum intake. Voluntary OM intakes of steers only differed between the milk stage diet and the dough stage diets. At low intake, the diets containing the more mature silage were more digestible. At high intake, the OM of diet containing the early dough stage silage was most digestible. Increased intake caused a depression in digestibility of different feed fractions. The magnitude of the depression varied among diets and fractions. Data indicated that the nutritive value of diets based on whole crop wheat silage is affected by stage of maturity, animal species, and amount of intake. The assessment of the crop wheat silage should therefore be made with the animal species and at the amount of intake for which the diets are intended.

Die Metabolisierung vond(−)Milchsäure wurde an freiwilligen Versuchspersonen nach Aufnahme vondl-Lactat anhand der renalen Ausscheidung sowie an Ratten und an Rattenleber in vitro mittels der Oxydationsrate von14C-d-Lactat zu14CO2untersucht. Bei 5 Probanden wurden nach Aufnahme von 1,6–6,5 mmold-Lactat pro kg0,75(entspr. 50–200 mg/kg) im Mittel 1,2–2,2 % der Dosis mit dem Harn ausgeschieden. Die exponentielle Abnahme der renalen Elimination in den ersten 15 h nach Aufnahme und die Ausscheidungsdauer bis zu 24 h (und ggf. darüber) ließen auf eine recht langsame Metabolisierung schließen. Bei Ratten war die Oxydationsrate vond-Lactat gegenüberl-Lactat nach intraperitonealer Dosis von 2,0 und 4,2 mmol pro kg0,75(entspr. ca. 62 bzw. 131 mg/kg Mensch) deutlich bzw. stark herabgesetzt. Nach intragastraler Gabe von 4,2–12,8 mmold-Lactat pro kg0,75(alsdl) wurden im Mittel 0,9 % alsd-Lactat und 2,4 % als Metaboliten im Harn ausgeschieden. Die Oxydation vond-Lactat zu CO2erstreckte sich schon nach der niedrigsten Dosis weit über 8 h und wurde bei höheren Gaben unterdrückt. In Gewebeschnitten von Rattenleber in vitro hemmten Oxalat,l-Lactat und Pyruvat die Oxydation vond-Lactat. Der Hemmeffekt vonl-Lactat betrug schon bei physiologischer Konzentration 20%. Eine signifikante Zunahme derd-Lactat Oxydation mit dem Körpergewicht und eine signifikant höhered-Lactat-Oxydation in der Leber von konventionellen gegenüber keimfreien Tieren machten Einflüsse der Alters und der Darmflora auf dend-Milchsäure-Stoffwechsel deutlich. Aus den Ergebnissen wird gefolgert, daßd-Milchsäure nur langsam metabolisiert werden kann, wenn erhöhte Konzentrationen des einen oder anderen Lactatisomers vorliegen. The metabolization ofd-lactate was examined in volunteers by means of renal excretion after intake ofdl-lactate, and in rats as well as in rat liver in vitro by the oxidation rate of14C-d-lactete to14CO2. In five volunteers after intake ofdl-lactate containing 1.60 to 6.5 mmold-lactate per kg0.75(equiv. to 50–200 mg/kg) an average of 1.2–2.2 percent of the dose was eliminated in urine. The exponential decline of renal elimination during the first 15 hours after intake and the total excretion time up to 24 hours (and possibly more) suggested a quite slow rate of metabolism. Following intraperitoneal injection of 2.0 and 4.2 mmol per kg0.75in rats (equiv. to 62 and 131 mg per kg in man) the oxidation rate ofd-lactate vs. L-lactate was significantly and strongly reduced. After intragastral dosage ofdl-lactate containing 4.2 to 12.8 mmold-lactate per kg0.75an average of 0.9 and 2.4 percent were excreted in urine asd-lactate and as metabolites. Even after the lowest dosed-lactate oxidation to CO2extended far beyond 8 hours. Higher doses decreased the rate ofd-lactate oxidation. In tissue samples of rat liver in vitro oxalate,l-lactate and pyruvate inhibited the oxidation ofd-lactate.l-lactate in a physiological concentration was sufficient to effect an inhibition of 20 percent. A significant increase ofd-lactate oxidation with increasing body weight and a significantly higher oxidation ofd-lactate in conventionals vs. germ-free rats indicated the influences of age and gastro-intestinal flora ond-lactate metabolism. From these results it is concluded thatd-lactic acid is only slowly metabolized if the concentration of one or other of the lactate isomers is elevated.

Im Rahmen einer Untersuchung zur prophylaktischen Wirksamkeit von spezifischen Dotterantikörpern bei erregerbedingten Kälberdurchfällen wurde auch die Absorption der unspezifischen heterologen aviären Dotterantikörper (cIgG) und deren Wirkung auf die Aufnahme von maternalen bovinen Kolostrumantikörpern (bIgG) überprüft. Zwei Gruppen von neugeborenen Kälbern wurde sprühgetrocknetes Volleipulver ab der ersten Tränke in einer Dosierung entweder von 16 g oder von 8 g pro Tag während der ersten 10 Lebenstage verabreicht. Eine dritte Gruppe diente als Kontrolle und erhielt kein Eipulver. Von insgesamt 123 Kälbern (5 bis 10 Kälber pro Entnahmezeitpunkt) wurden 6, 12, 24, 48, 72 bzw. 96 Stunden post natum Blutproben genommen. Bei beiden Eipulverdosierungen wurden die höchsten Hühner-IgG-Konzentrationen (3,1 µg bzw. 1,2 µg pro ml Serum) jeweils 12 Stunden post natum ermittelt. Diese cIgG-Konzentrationen nahmen danach kontinuierlich auf Konzentrationen von 1,1 µg bzw. 0,2 µg pro ml Serum zum Zeitpunkt 96 Stunden post natum ab. Bezogen auf die mit der ersten Tränke verabreichte bIgG- bzw. cIgG-Menge wurde überschlagsweise zum Zeitpunkt 6te Lebensstunde eine Anflutung im Blut von 23 % (bIgG) bzw. von 7 % und 6 % (cIgG) errechnet. Der zeitliche Verlauf (6te bis 96te Stunde) der Konzentration des bovinen IgGs in den Blutproben war vergleichsweise stabil und lag durchschnittlich bei 5,9 mg pro ml Serum, wobei das Plateau bereits nach 6 Stunden erreicht war. Signifikante Unterschiede zwischen den bIgG-Werten der Kälber, die Dotterantikörper bekamen (6,2 bzw. 6,1 mg pro ml Serum), und denen der Kontrollgruppe (5,4 mg pro ml Serum) waren nicht zu beobachten. Eipulver kann somit offensichtlich zur Prophylaxe bei neugeborenen Kälbern ohne Beeinträchtigung der Absorption der kolostralen Antikörper verabreicht werden. Allerdings muß bei einer Eipulververgabe mit der ersten Tränke auch mit einer Absorption von aviären Dotterantikörpern gerechnet werden. Studying the prophylactic effects of specific yolk antibodies against diarrhea in newborn calves, also the intestinal absorption of unspecific heterogeneous avian antibodies as well as their effects on the uptake of maternal bovine colostral antibodies (bIgG) was investigated. Two groups of newborn calves received egg powder (16 g or 8 g per day) for the first 10 days of their life beginning with the first meal. A third group was kept as a control without any egg powder in their diet. Blood samples (5 to 10 calves per sampling time) were taken from 123 calves at 6, 12, 24, 48, or 96 h postnatally. With both doses the highest chicken IgG (cIgG) levels (3.1 µg resp. 1.2 µg per ml serum) have been measured 12 h after birth. These concentrations decreased continuously to the levels of 1.1 µg resp. 0.2 µg cIgG per ml serum at 96 h postnatally. The uptake into blood at 6 h postnatally has roughly been estimated as approximately 23 % (bIgG) and 7 % resp. 6 % (cIgG) of the IgG dosages given with the first meal. The time-course (6 to 96 h) of the bIgG level in blood was quite stable, plateauing already after 6 h at a mean of 5.9 mg per ml serum. Significant differences between the bIgG levels of calves with yolk antibodies in their diet (6.2 resp. 6.1 mg bIgG per ml serum) and those of the control group (5.4 mg per ml serum) could not be observed. Obviously, the prophylactic use of egg powder in newborn calves has no negative effect on the absorption of colostral antibodies. However, with the feeding of chicken egg yolk antibodies already with the first meal also the absorption of avian antibodies has to be taken into consideration.

An 8 Dalmatiner-Hunden werden exogene Einflüsse (Puringehalte der Diät, Xylit-Infusion) auf die Harnsäurekonzentration im Blutplasma sowie Beziehungen zwischen Purinaufnahme und -ausscheidung untersucht. Steigende Purinaufnahme bewirkte einen linearen Anstieg der renalen Exkretion von Harnsäure (r=0,952) und weniger steil von Allantoin (r=0,901). An je 2 Tieren mit niedriger und hoher Purinaufnahme werden mittels Dauerinfusion von (2-14C)-Harnsäure die metabolischen Flüsse im Steady state gemessen. Die extrarenale Exkretionsrate von Harnsäure + Allantoin bei purinarmer und purinreicher Ernährung betrug 2,9 % bzw. 8,5 % der Eintrittsrate. Die Ergebnisse werden vergleichend mit Daten vom Menschen diskutiert und bemerkenswert gute Übereinstimmungen festgestellt. In eight Dalmatian dogs exogenous effects (dietary purine, xylit infusion) on plasma uric acid were examined and relationships between purine intake and excretion were established. Increasing purine intake resulted in a linear increase in renal excretion of urate (r=0.952) and a less steep increase of allantoin (r=0.901). In pairs of two animals with low and high purine intakes the metabolic fluxes in steady state were measured by continuous infusion of (2-14C) urate. The extrarenal excretion rates of urate + allantoin during high-purine and low purine feeding averaged 2.9 % and 8.5 % of entry rates. The results are discussed in comparison with human data and a remarkably good agreement is observed.

Vitamin D metabolites can prevent estrogen depletion-induced bone loss in ovariectomized (OVX) rats. Our aim was to compare the bone-protective effects of 1α,25-dihydroxyvitamin D3(1,25(OH)2D3), 1α,25-dihydroxyvitamin D2(1,25(OH)2D2), 1α-hydroxyvitamin D3(1α(OH)D3), and 1α-hydroxyvitamin D2(1α(OH)D2) in OVX rats. 1α(OH)D3and 1α(OH)D2are thought to be activated in the liver to form 1,25(OH)2D3and 1,25(OH)2D2, respectively. Forty-four 12-week-old female Fischer-344 rats were either OVX or sham-operated (SHAM). Groups of OVX rats (n = 7 each) received vehicle alone, 1,25(OH)2D3, 1,25(OH)2D2, 1α(OH)D3, or 1α(OH)D2, starting 2 weeks after surgery. All vitamin D metabolites were administered orally at a dose of 15 ng/day/rat. Urine and blood samples were collected 6, 9, 12, and 16 weeks after surgery. Serum samples were analyzed for total calcium and phosphate. Calcium, phosphate, creatinine, and free collagen cross-links (ELISA) were determined in urine. After tetracycline double labeling, the rats were sacrificed 16 weeks postsurgery, and the proximal tibiae and the first lumbar vertebrae were processed undecalcified for static and dynamic bone histomorphometry. 1,25(OH)2D3and, to a slightly lesser extent, 1,25(OH)2D2elevated vertebral cancellous bone mass in OVX rats to a level beyond that observed in SHAM animals, and both compounds increased serum calcium and urinary calcium excretion to similar extents. 1α(OH)D3and 1α(OH)D2resulted in a 64% and 84%, respectively, inhibition of ovariectomy-induced vertebral cancellous bone loss. In the proximal tibial metaphysis, all vitamin D metabolites tested could only partially prevent post-OVX trabecular bone loss, with a tendency for 1α(OH)D3to be the least active compound. The effects of 1α(OH)D3and 1α(OH)D2on calcium homeostasis differed markedly, however. The mean increase in urinary calcium excretion over the whole experiment was fivefold for 1α(OH)D3, whereas the corresponding increase for 1α(OH)D2was only twofold. We conclude that, compared with 1α(OH)D3, 1α(OH)D2combined at least equal or higher bone-protective activity in OVX rats with distinctly less pronounced effects on calcium homeostasis. This effect was not due to a differential action of the corresponding main activation products, 1,25(OH)2D3and 1,25(OH)2D2.

Vitamin D metabolites can prevent estrogen depletion-induced bone loss in ovariectomized (OVX) rats. In this study, we investigated the bone-sparing effects of oral 1α,24R,25-trihydroxyvitamin D3(1,24,25(OH)3D3) in a wide dose range in aged OVX rats. Fifty-three female Fischer-344 rats (6 months old, 170 g BW) were either ovariectomized or sham-operated (SHAM). Eight rats served as baseline controls. Groups of OVX rats (n= 7–8 each) received vehicle alone or graded oral doses of 1,24,25(OH)3D3(0.05, 0.1, 0.2, and 0.3 μg/kg BW/day), starting five days after surgery. Urine and blood samples were collected one, two, three, and four months after surgery. Serum samples were analyzed for total calcium and alkaline phosphatase. Calcium, hydroxyproline, and collagen crosslinks (HPLC) were determined in urine. After fluorochrome double labeling, the rats were sacrificed four months postsurgery and the first lumbar vertebrae and the proximal tibiae were processed undecalcified for bone histomorphometry. Ovariectomy induced a 28% and a 69% reduction in vertebral and tibial cancellous bone area, respectively. Osteopenia in OVX rats was associated with increased histomorphometric and biochemical indices of bone turnover. The administration of 1,24,25(OH)3D3to OVX rats dose-dependently increased vertebral and tibial cancellous bone mass, serum calcium, and urinary calcium excretion, and reduced histomorphometric and biochemical indices of bone resorption. 1,24,25(OH)3D3at doses of 0.2 and 0.3 μg/kg/day produced strong anabolic effects, especially on vertebral cancellous bone in OVX rats, and increased mineral apposition rate and wall width of completed remodeling units relative to vehicle-treated OVX rats. Even at high doses, 1,24,25(OH)3D3did not impair bone mineralization. We conclude that oral administration of 1,24,25(OH)3D3can effectively prevent estrogen depletion-induced cancellous bone osteopenia in the aged OVX rat model. The therapeutic window for 1,24,25(OH)3D3in OVX rats, however, is also narrow, comparable to that for calcitriol.

An 12 Milchkühen wurde der Einfluß von Laktationsstadium, Fütterungsniveau und Rationszusammensetzung auf die Passage des Verdauungsbreis aus dem Reticulorumen untersucht. Es wurden gemischte Konzentratfutter: Rauhfutter‐Rationen verfüttert, wobei die Rauhfutterkomponenten aus Maisganz‐pflanzensilage und extensiv bzw. intensiv produzierter Grassilage im Verhältnis 40: 60 (Frischsubstanzbasis) bestanden und das durchschnittliche Konzentratfutter: Rauhfutter‐Verhältnis der Rationen 34: 66 in der Trockensubstanz betrug. Als Marker wurde Titan(IV)‐oxid (TiO2) eingesetzt, dessen Konzentration im Kot nach oraler Verabreichung über 120 h hinweg ermittelt wurde. Probenahmen erfolgten in vier Untersuchungszeiträumen (Perioden) ‐ ante partum(1 Periode) und in der ersten Laktationshälfte (3 Perioden) ‐, die jeweils einen bestimmten physiologischen Zustand charakterisierten. Die Fütterung der Tiere erfolgte leistungsgerecht mit durchschnittlichen Trockensubstanzaufnahmen von 12,0; 16,8; 22,6 und 21,2 kg in den jeweiligen Untersuchungszeiträumen. Passageparameter wurden mit Hilfe unterschiedlicher Schätzverfahren ermittelt, wobei ein Modell mit Gamma‐Zeitabhängigkeit (G4G1), ein exponentielles Modell sowie ein Modell, in dem die mittlere Verweildauer des Markers im gesamten Verdauungstrakt als Mittelwert aller Punkte der Marker‐Exkretionskurve berechnet wird, verwendet und verglichen wurden. Die Ergebnisse zeigten eine deutliche Beschleunigung der Passage des Markers aus dem Reticulorumen von ante partumnach post partum.Zwischen G4G1 und dem Modell, das auf die Verwendung des Mittelwertes Bezug nimmt, zeigte sich eine gute Übereinstimmung. Dagegen war die Übereinstimmung zwischen G4G1 und dem exponentiellen Modell schlechter. Effekte von Periode und Ration waren post partumnur für die Passagerate aus dem und für die mittlere Verweildauer im schnellen Kompartiment (beide geschätzt nach G4G1) nachzuweisen. TiO2scheint als externer Marker zur Ermittlung von Passageraten gut einsetzbar zu sein, wobei die Größenordnung der Werte im Bereich der Passage von Konzentratfutterteilchen liegen dürfte.

Abstract.: It was the aim of the present study to investigate whether a 2-month prophylaxis of postovariectomy bone loss with low-dose calcitriol would have long-lasting beneficial effects on cancellous bone mass or structure after its withdrawal in rats. Six-month-old female Fischer 344 rats were either ovariectomized (OVX) or sham-operated (SHAM). Groups of SHAM and OVX rats were orally treated with either 0.05 μg calcitriol/kg per day or vehicle for 2 months postovariectomy, starting immediately after ovariectomy. Thereafter, the rats were maintained without treatment for another 4 months. Half the animals in each group were killed 2 months postovariectomy; the rest of the rats were killed 6 months postovariectomy. Cancellous bone histomorphometry was performed on the first lumbar vertebral body and on the proximal tibial metaphysis. Administration of low-dose calcitriol to SHAM and OVX rats resulted in hypercalciuria, but not hypercalcemia. By 2 months postovariectomy, calcitriol treatment of OVX rats had completely prevented tibial trabecular bone loss, and had increased vertebral cancellous bone mass in SHAM and OVX rats by about 30% over the level observed in SHAM vehicle controls. However, at the end of the experiment, i.e. 4 months after withdrawal of calcitriol, cancellous bone mass and structure in both the vertebrae and the tibiae of calcitriol-treated OVX rats were almost identical to those of vehicle-treated OVX rats. We conclude that prevention of bone loss with low-dose calcitriol during the phase of acute estrogen deficiency, when bone turnover is maximally increased, does not provide long-term beneficial effects on cancellous bone mass or structure in OVX rats. If extrapolated to postmenopausal women, this study would suggest that prophylaxis against postmenopausal bone loss with short-acting antiresorptive substances during only the first few years after menopause will probably not reduce the risk of postmenopausal osteoporosis later in life.

In rabbits the influence of the reingestion of special faeces on gastric as well as on intermediary metabolism of [U-14C]-D(-) lactic acid has been studied.In unrestrained animals there was no naturally occurring D(-) lactic acid concentration measurable either in stomach contents or in blood. Orally loaded D(-) lactate was almost completely decomposed in the stomach and absorbed within 15 min. Thereintermediary oxidation was equally affected. Thus, in rabbits prevented from caecotrophy the exhalation rate of 14CO2 derived from [14C]-D(-) lactic acid at 2 h after oral application was reduced to about 65% of the rate of unrestrained animals. Similar low oxidation rates have been obtained only if [14C]-D(-) lactate was injected intraperitoneally.One can conclude from these experiments that caecotrophy in rabbits prevents the accumulation of D(-) lactic acid in the stomach rapid bacterial transformation but increases the rate of its intermediary oxidation absorption of these transformation products.

Two simple, high-yield rapid methods with good reproducibility are described, which permit the determination of radioactivity in plasma D-(—)-3-hydroxybutyrate. The compound is converted to acetoacetate, using a modified enzymatic method. In procedure 1, acetoacetate is reacted with 2, 4-dinitrophenylhydrazine; the resulting hydrazone is oxidised by means of a sample oxidiser, and the product 14CO2is collected in scintillation liquid and counted. In procedure 2, a Conway microdiffusion unit is applied. The acetoacetate is decarboxylated to acetone in the presence of o-phenylenediamine, and the acetone is then diffused into semicarbazide solution. This solution, containing the semicarbazone derivative of labelled acetone, is transferred to liquid scintillation and counted. In both procedures the radioactivity is measured simultaneously in a separate sample which was not subjected to the enzymatic conversion of D-(–)-3-hydroxybutyrate. The difference in radioactivity between the two samples is attributed to labelled D-(–)-3-hydroxybutyrate.