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Biomedical subjects

J Carlsson

Publications and source records attributed to J Carlsson.

At least 163 records · Page 9Linked to original sources

Oxygen-dependent modulation of release and activity of polymorphonuclear leukocyte granule products.

Polymorphonuclear leukocytes are important in the defense against the anaerobic microflora of infected gingival pockets. One part of this defense is release of antibacterial granule products by polymorphonuclear leukocytes into the pockets. The aim of the present study was to compare the efficiency of polymorphonuclear leukocytes in releasing granule products under aerobic and anaerobic conditions. Polymorphonuclear leukocytes were exposed to serum-opsonized zymosan under aerobic and anaerobic conditions. The levels of released granule products were determined by combining measurements of activity with enzyme-linked immunosorbent assays. The level of released elastase was twice as high in anaerobic as in aerobic reaction mixtures. A similar difference was not detected for myeloperoxidase. However, myeloperoxidase was inactivated after its release under aerobic conditions. The release of lactoferrin was an efficient under aerobic as under anaerobic conditions. The effect of aerobic conditions on the release of elastase and the inactivation of myeloperoxidase could be ascribed to oxidants formed in the myeloperoxidase-H2O2-chloride system. Also, the activity of the released cytoplasmic enzyme lactate dehydrogenase was inactivated by oxidants formed in the myeloperoxidase-H2O2-chloride system. These findings suggest that, in the anaerobic environment of the gingival pocket, elastase and possibly also other azurophilic granule products are released in higher amounts than under fully oxygenated conditions. In this environment, the released products may also escape inactivation by the myeloperoxidase-H2O2-chloride system.

Aerobiosis↗

Utilization of glutathione (L-gamma-glutamyl-L-cysteinylglycine) by Fusobacterium nucleatum subspecies nucleatum.

Although fusobacteria use amino acids and peptides as energy source, it is not known whether they are able to actively transport peptides into the cell. In the present study the tripeptide glutathione was used as a model substance to investigate peptide uptake in Fusobacterium nucleatum subsp. nucleatum. Cells harvested after 2 days of growth on blood agar or in their exponential growth phase in broth were suspended in buffer with glutathione, L-cysteinylglycine and L-cysteine. As a measure of cell uptake, the formation of hydrogen sulfide was followed. Cells from blood agar had a low capacity to form hydrogen sulfide from the tripeptide glutathione and the dipeptide L-cysteinylglycine. However, hydrogen sulfide was formed from L-cysteinylglycine, but not from glutathione or from L-cysteine, by cells grown in broth in such a way that it strongly indicated an active transport of L-cysteinylglycine with a Km of 18 microM. Hydrogen sulfide was efficiently formed from glutathione by cells grown in broth in the presence 1 mM glutathione. In these cells a glycylglycine-dependent L-gamma-glutamyl peptidase activity was induced. It is probable that the efficient utilization of glutathione for hydrogen sulfide formation mirrored the uptake of L-cysteinylglycine after an L-gamma-glutamyl peptidase had split L-glutamate off from glutathione.

Biological Transport, Active↗

Dose enhancement in fast neutron tumour therapy due to neutron captures in 10B.

High energy neutrons, applied in fast neutron tumour therapy, lose energy when passing through tissue and are at the end of their trajectories captured in nitrogen, hydrogen or other normally occurring elements. If the tissue contains 10B, which has a very high cross section for capture of thermal neutrons, then disintegration products of this process, helium and lithium ions, give a dose enhancement which, if the boron is targeted to tumour cells, may be beneficial. The dose enhancement was in the present study calculated as a function of the 10B concentration in the cells and as a function of different thermal neutron fluencies. If the tumour cells contained 10 or 100 microns 10B/g the average dose enhancement was about 20 or 200 mGy respectively. This was obtained with the thermal neutron fluency 2.0 x 10(10) n/cm2. The relative biological effectiveness of the neutron capture process is unknown but assuming the factor 2, these doses correspond to 0.04 or 0.4 CGE (cobolt-60 gray equivalent) respectively, which could directly be compared to the 2-3 Gy of low-LET radiation that is daily applied in conventional radiotherapy. However, if thermal or epithermal neutron fields are directly applied to the patients a hundred times higher thermal neutron fluency can be used. This gives, in the cases with 10 or 100 micrograms 10B/g, about a hundred times higher average doses so that 2-20 Gy, corresponding to about 4-40 CGE, can be given to the patients. Thus, a successful targeting with high amounts of 10B in the tumour cells gives a significant dose enhancement when applied in fast neutron therapy but it is then more reasonable to treat the patient directly with thermal or epithermal neutrons since the average dose enhancement in the latter case is about a hundred times higher and curable doses might be obtained by the tumour specific capture processes alone.

Boron Neutron Capture Therapy↗

Cellular binding of carboranylalanine and some effects of boron neutron capture. Analysis of cultured melanoma B16 cells.

The boron containing substances L- and D-carboranylalanine might be of interest for boron neutron capture therapy, BNCT. Cultured mouse melanoma B16 cells were analyzed regarding binding of these substances and some introductory studies on effects of thermal neutron irradiation were also carried out. Comparisons were made with two boron containing compounds, p-boronophenylalanine (BPA) and boronated thiouracil (BTU-1), previously proposed for BNCT of melanomas. The results showed that both L- and D-carboranylalanine bound well in the B16 cells whereas BTU-1 gave no, and BPA only a low, binding. Thus, both forms of carboranes bound better than the two previously proposed substances. The carboranes also bound rather well in two tested human melanoma cell lines, IGR1 and RPMI-7951. Both L- and D-carboranylalanine showed a certain binding to isolated melanin but were not incorporated during melanin synthesis. Cultured glioma cells, used for comparison, bound BPA and to some extent the carboranes. This indicates that the substances are not melanoma specific. The carboranes caused some acute detachment of monolayer growing cells but were not strongly toxic since they did not reduce the growth rate. The cells treated with L-carboranylalanine or BPA showed, after neutron irradiation, a clear decrease in survival compared to the controls whereas no or only small effects were seen for cells treated with D-carboranylalanine or BTU-1. These results were conflicting since BPA gave therapeutical effects although only small amounts were bound while D-carboranylalanine gave no significant therapeutical effect in spite of better binding. One explanation might be different intracellular localizations. This has to be studied in more detail.

Animals↗

[Prehospital thrombolytic therapy of acute myocardial infarct].

The extent of myocardial damage occurring during acute myocardial infarction is time dependent, and there is abundant evidence from most clinical trials that mortality reduction is greatest in patients treated early with thrombolytic agents, although beneficial effects have been shown with treatment initiated up to 12 hours after onset of symptoms. This temporal dependence of benefit was most clearly seen with the 47% mortality reduction obtained with streptokinase given within the first hour in the GISSI-1 trial (Table 1). The process of infarction may be completely aborted if reperfusion is initiated within 30 minutes after symptom onset. Current approaches designed to reduce the time delay between onset of symptoms and the initiation of thrombolytic treatment include increasing public awareness of the need to seek prompt medical attention in the event of chest pain, reducing in-hospital delays in initiation of thrombolytic therapy, and administration of thrombolytic agents in the prehospital setting. Since the first paper on prehospital thrombolysis by Koren et al. in 1985 there have been numerous studies published, including several randomized trials comparing prehospital and in-hospital initiation of thrombolytic therapy (Table 2). In randomized studies patients received in the pre-hospital phase either a bolus or infusion with the thrombolytic agent followed by placebo after hospital admission, or placebo when first seen outside the hospital, followed by the thrombolytic agent after arrival at the hospital. This was performed in a double-blind fashion in some of the trials. Some of the studies on prehospital thrombolysis have focused only on feasibility and safety, others on time gain, differences in ejection fraction and mortality benefit. Almost all have conclusively shown the practicability and safety of patient selection and administration of the thrombolytic agent. This positive result was observed in different organizational types of the emergency system: In the Myocardial Infarction Triage and Intervention trial (MITI) patients with chest pain were screened by paramedics using a checklist of clinical inclusion and exclusion criteria. The paramedics then obtained a computer-interpreted ECG which was transmitted to the emergency department in the hospital where a physician made the decision on the form of treatment. The thrombolytic agent was then administered by the paramedic. In the European Myocardial Infarction Project (EMIP) an emergency physician was personally present and responsible in the prehospital setting, whereas in the Grampian Region Early Anistreplase Trial (GREAT) general practitioners made the decision for enrolling the patient.

Double-Blind Method↗

The influence of the dietary balance between energy and protein on milk urea concentration. Experimental trials assessed by two different protein evaluation systems.

Twenty-three dairy cows were fed rations with different proportions of energy and digestible crude protein (DCP). When the ration was balanced for energy and DCP according to Swedish standard the cows' milk urea concentration was 4.66-4.92 mmol/l (95% CI of mean). With increasing intakes of DCP, fed together with standard levels of energy, the mean milk urea concentration increased in proportion to the surplus of DCP. In contrast, the concentration of urea decreased when the cows were overfed with energy at the same time as they were underfed with protein. When the rations were recalculated in accordance with the AAT/PBV system for dietary protein evaluation the 95% CI for the mean milk urea concentration of the cows receiving a balanced ration was 3.76-4.56 mmol/l. The concentration of urea was dependent primarily on the PBV. When the 2 protein evaluation systems were compared there was a strong correlation between PBV and DCP. Ammonia was the only constituent of the rumen whose concentration was strongly correlated with the milk urea concentration. Taken together with earlier data the present results suggest that a milk urea concentration between 4.0 and 5.5 mmol/l should be regarded as normal at least when cows are fed conventional feedstuffs.

Animal Feed↗

New carborane-based compounds for boron neutron capture therapy: binding and toxicity of ANC-1, DAC-1 and B-Et-11-OMe in cultured human glioma and mouse melanoma cells.

The toxicity and binding of the three new carborane based compounds: 2 (1,2-dicarba-closo-dodecaborane (12)-1(-yl-methoxy)-2-(3-amino-propyl))-1,3-propanediol, called DAC-1; 7-(3-amino-propyl)-7,8-dicarba-nido-undecarborate (-1) called ANC-1; and rac-1-(9-o-carboranyl)-nonyl-2-methyl-glycero-3- phosphocholine, called B-Et-11-OMe, were analyzed with cultured human glioma cells, U-343MGa, and mouse melanoma cells, B16, as biological models. The previously developed compound di-sodium undecahydro-mercapto-closo-dodecarborate (BSH), which is tested for therapy of malignant gliomas, was analyzed for comparison. In the toxicity tests the cells were exposed to the substances at cell culture medium concentrations in the range 0-50 ppm boron for 1 or 20 h and thereafter analyzed regarding growth. Growth-disturbing effects were seen for the two compounds DAC-1 and B-Et-11-OMe at the concentrations corresponding to 15 and 50 ppm boron, respectively. The compounds ANC-1 and BSH showed no growth-disturbing effects at the tested concentrations. In the binding tests, the cells were incubated for 20 h at about the highest compound concentrations that did not cause growth disturbances. The boron content in the cells was then determined by inductively coupled plasma-atomic emission spectrometry (ICP-AES) and in some cases ICP-mass spectrometry (ICP-MS). The most extensive binding was seen for DAC-1 and B-Et-11-OMe, which accumulated boron to about 100 and 60 times, respectively, compared with the concentration in the culture medium. The compound ANC-1 also accumulated boron in the cells but the boron could be easily washed out indicating no or only a weak binding. BSH did not accumulate. Further analysis should be made regarding biological properties such as intracellular compartmentalization, metabolic interference and tumor specificity of the compounds DAC-1 and B-Et-11-OMe.

Animals↗

The diurnal variation of urea in cow's milk and how milk fat content, storage and preservation affects analysis by a flow injection technique.

Six Swedish Red and White dairy cows, producing 20-39 kg of 4% fat-corrected milk were given a ration balanced in energy and protein. They had access to feed from 05.15 to 09.00 and from 13.00 to 16.30 and were milked at 06.15 and 15.30. The milk was analysed for urea with a FIA technique. There was a significant diurnal variation in milk urea. The highest values were found 3-5 h after the beginning of the morning feeding and the lowest values (down to 60% of the max. values) during late night. Within 1 h after the start of the morning feeding the urea values had increased significantly, but they had decreased within the same time after the start of the afternoon feeding. Since there was a pronounced diurnal variation in the milk fat content, the urea concentration was also recalculated to concentration in the water phase of the milk. It was higher in that phase, but the pattern of the diurnal variation was not changed significantly. However, analyses on milk with a very high fat content may give misleading results. There were no important differences in the milk urea concentration of different udder quarters. When calculated as concentration in the water phase of the milk, no differences in urea concentration were found between the beginning and the end of milking. The analytical method had a good precision (coefficient of variation max. 3%). The milk urea concentration was not changed significantly after storage during 10 days at 4 degrees C when no preservative was added; but after 17 days the milk had turned sour and the urea value had increased. When a preservative (bronopole) was added the urea concentration remained unchanged during 17 days. Deepfreezing did not influence the urea concentration.

Animals↗

Relative biological effectiveness of intermediate energy protons. Comparisons with 60Co gamma-radiation using two cell lines.

Range modulated proton beams are used for radiotherapy of malignant tumours at several accelerator laboratories with the aim of introducing proton therapy as a clinical hospital-based therapy modality. Due to the finite range and the sharpness of the dose gradients, the dose to well defined target volumes can be raised without excessive irradiation of non-target tissue. The prescribed proton doses are determined in part on the basis of the relative biological effectiveness (RBE) of the particular radiation quality. In this study, RBE values were determined for a proton beam with a maximal range of 33 mm, which corresponds to an energy of approximately 67 MeV. The range modulated depth-dose distribution, with a 20 mm extended Bragg peak, was mainly designed for high precision treatment of small targets such as uveal melanomas. The tested cell lines, LS-174T and V79-379A, were chosen because of their suitability for clonogenic assays. The cells were irradiated with single doses in the range 2-10 Gy at different depths in the extended peak region of the range modulated proton beam. RBE values were determined by comparing the doses needed to obtain the same reduction in colony formation (0.5, 0.1 and 0.01) as with the reference 60Co gamma source. The mean RBE value was 1.22 with a standard deviation of 0.08. The variations depended on both cell type and on the survival levels considered.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The red cell membrane and invasion by malarial parasites.

The red cell membrane with its bilipid layer, integral membrane proteins (especially the GPs and band 3), and the red cell skeleton pose a formidable barrier for the malarial parasite to overcome during invasion. Invasion is an ordered and sequential process, indicating a highly complex and specific process involving numerous molecular interactions. For P. vivax and P. knowlesi infections the Duffy glycoprotein seems to be a specific requirement in invasion. For P. falciparum the GPs, and especially the N-acetyl neuraminic acid linked in an alpha 2-3 configuration on them, appear to act as specific ligands although some strains of P. falciparum may use alternate ligands for invasion. The parasite enters the red cells within an invagination continuous with the red cell bilipid layer, the parasitophorous vacuole membrane, and recent evidence would indicate that this membrane is largely of parasite origin. The numerous occasions in which the red cell needs to deform during invasion indicates that membrane deformability could be an important factor in determining invasion, but the dissociation of invasion and deformability as induced by a number of reagents would not support this contention. Instead it is suggested that reagents which modify invasion may be acting via alterations in red cell or parasite protein phosphorylation or dephosphorylation.

Amino Acid Sequence↗

Penetration and binding of epidermal growth factor-dextran conjugates in spheroids of human glioma origin.

Targeting with toxic EGF-based conjugates against tumour cells with amplified EGF-receptors might be a possible approach towards improved therapy of certain malignancies such as gliomas and squamous carcinomas. In this study, the penetration and binding of 125I delivered by EGF-dextran conjugates were analysed in cultured spheroids applied as a tumour nodule model. The spheroids consisted of human glioma cells, U-343MGaCl2:6, with large amounts of EGF-receptors. The penetration and binding patterns of 125I delivered by 125I-EGF and 125I-dextran were analysed for comparison. The EGF-dextran associated 125I-activity showed a rather slow penetration but after some hours significant amounts of radioactivity had reached the deeper regions and good penetration was obtained within 5 hours. The penetration seemed somewhat faster when the 125I-activity was delivered with EGF possibly dependent on the lower molecular weight allowing for faster diffusion. Furthermore, EGF-dextran associated 125I seemed to penetrate somewhat faster after the EGF-receptors were blocked with non-radioactive EGF, probably due to the lack of binding preventing free diffusion. After administration of 125I-EGF-dextran or 125I-EGF, the binding patterns were superimposed on the penetration patterns. In the penetration studies, the superimposed accumulations due to binding were removed by presaturation of the receptors with non-radioactive EGF. After a 1 hour incubation, binding of EGF-dextran associated 125I-activity could be seen only in an outer region, with an approximative thickness of 50 microns, of the viable cell layer. Extensive receptor specific binding in the deeper regions, at a depth of 100-200 microns, was seen after several hours incubation. In addition, low levels of non-specific binding in the central regions were seen when the 125I-activity was delivered with dextran without EGF. A similar low background binding was seen also in the centre of spheroids incubated with 125I-EGF-dextran or 125I-EGF after saturation of the receptors with non-radioactive EGF. However, the major amount of radioactivity delivered as 125I-EGF-dextran or 125I-EGF had a receptor specific binding and, also in inner regions, it could be displaced by non-radioactive EGF. Thus, EGF-dextran, which is a candidate compound for targeted therapy, allowed penetration of the applied radioactivity and binding could be observed, after some hours, also in the inner regions of the spheroids.

Dextrans↗

Binding, internalization and excretion of TGF alpha-dextran associated radioactivity in cultured human glioma cells.

Conjugates based on transforming growth factor alpha, TGF alpha, or epidermal growth factor, EGF, are candidates for targeted radiotherapy against EGF-receptor rich tumours such as gliomas or squamous carcinomas. In this study, binding, internalization and excretion of radiolabelled TGF alpha and TGF alpha-dextran conjugates was analysed in an EGF-receptor rich human glioma cell line. The binding of 125I-TGF alpha was EGF-receptor specific and the binding pattern was similar to that of 125I-EGF. The TGF alpha-dextran conjugate also bound specifically but gave maximum binding for a longer time during continuous incubation compared to when only TGF alpha was used. The excretion pattern of internalized radioactivity was somewhat slower for 125I-TGF alpha-dextran, with 125I-labelling on the TGF alpha part, as compared to 125I-TGF alpha although most of the radioactivity in both cases was excreted within 4 hours. The fate of the dextran part of the conjugate, as followed by means of 125I-labelling of the dextran, was different since all radioactivity in that case remained cell-associated for at least up to 22 hours. Furthermore, by comparison with previously published results, it was seen that the radioactivity delivered through the TGF alpha part of TGF alpha-dextran was retained for a shorter period of time by the cells than when delivered by EGF in EGF-dextran conjugates. However, when the radioactivity was delivered by the dextran part of the conjugates, the radioactivity seemed to be retained equally well or even better when TGF alpha-dextran was applied. It is concluded that TGF alpha-dextran, as well as EGF-dextran, have interesting properties for targeting against EGF-receptors and that the dextran part is well retained in the cells and therefore might be a suitable carrier for toxic agents such as radionuclides. It is of high interest to continue with toxicological and pharmacological in vivo studies of the conjugates.

Binding Sites↗

Penetration and binding of L- and D-carboranylalanine in human melanoma spheroids.

The principle of boron neutron capture therapy (BNCT) is that a cell-specific 10B-containing substance binds to tumour cells and irradiation with thermal neutrons is performed when the 10B concentration, in relation to the levels in critical normal tissues, is at a maximum. Some boron compounds have recently been proposed for BNCT of malignant melanomas; the synthesized L- and D- forms of carboranylalanine and the previously tested compound L-p-boronophenylalanine are candidates. Human melanoma, IGR1, spheroids were used as models of melanoma nodules in this study. The spheroids developed central necrosis when they were about 480 microns in diameter and the volume doubling time was 2.6 +/- 0.3 days. The tritiated thymidine labelling index decreased rapidly as a function of distance from the periphery and was, at a depth of 175 microns, close to zero. The penetration patterns showed, for L- and D-carboranylalanine and L-p-boronophenylalanine, a homogeneous distribution of 10B throughout the spheroids by 5 min. L-Carboranylalanine gave a more or less even binding of 10B throughout the spheroids and large amounts were present also in the central necrotic regions. D-Carboranylalanine also gave a homogeneous 10B binding in the viable cell layers while the binding in the central necrotic area was lower and a similar, but somewhat lower, binding was found for L-p-boronophenylalanine. Thus, there were no penetration barriers for the boron compounds and binding of 10B was found also in the deeper regions of the viable cell layers. The results showed that the new carboranylalanine compounds are of interest for further analysis, including toxicological and pharmacological studies in vivo.

Boron Compounds↗

Pathophysiological mechanisms for restenosis following coronary angioplasty: possible preventive alternatives.

Restenosis after successful percutaneous transluminal coronary angioplasty (PTCA) remains an unsolved medical problem. The search for the underlying pathophysiological mechanisms have identified intimal proliferation of smooth muscle cells (SMC) to be the prevailing cause of late restenosis, with endothelial cells (EC) and platelets being important participators in the process. According to the most accepted present theory, SMC would be stimulated to migrate and proliferate shortly after the angioplasty by the release of growth factors from injured EC and accumulated platelets. However, clinical trials of agents interfering with these mechanisms have not significantly diminished the rate of restenosis, which suggest both that our knowledge of the process is incomplete, and that new ways of administering the agents may be required.

Angioplasty, Balloon, Coronary↗

Peptostreptococcus micros has a uniquely high capacity to form hydrogen sulfide from glutathione.

There are high amounts of hydrogen sulfide in deep periodontal pockets. This volatile sulfur compound may be formed from L-cysteine, but only low levels of this amino acid can be expected to be present in periodontal pockets. Glutathione, L-gamma-glutamyl-L-cysteinylglycine, is in high concentration in most tissue cells, and this tripeptide may be more readily available as a source of hydrogen sulfide formation in the pockets. The ability of 37 different species of oral bacteria to utilize glutathione in hydrogen sulfide formation was studied. Of these species, only 2 species of Peptostreptococcus and 5 species of Fusobacterium formed high amounts of hydrogen sulfide from glutathione within 24 h. Since the initial rate of hydrogen sulfide formation was more than 5 times higher in Peptostreptococcus micros than in any of the other bacterial species, the kinetics of sulfide formation from glutathione by P. micros was further elucidated. The formation of sulfide followed quite closely hyperbolic Michaelis-Menten kinetics. The maximal initial rate of sulfide formation (Vmax) was 163 +/- 2 nmol sulfide per minute per milligram of cellular protein. Half maximal initial rate (Km) was obtained at 7.4 +/- 0.8 microM glutathione. The initial rate of sulfide formation from L-cysteine was much slower and was almost proportional to L-cysteine concentration. This difference in kinetics of sulfide formation between glutathione and L-cysteine strongly suggested that glutathione was actively transported into the cell, whereas the transport of L-cysteine was more or less controlled by diffusion. The sulfide formation from the dipeptide L-cysteinylglycine also followed quite closely hyperbolic Michaelis-Menten kinetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Transport, Active↗

Chemotaxis and degranulation of polymorphonuclear leukocytes in the presence of sulfide.

In polymicrobial infections such as periodontal disease, the polymorphonuclear leukocytes (PMN) may have to work in the absence of oxygen and in the presence of significant levels of hydrogen sulfide. There are conflicting results reported on the chemotactic capacity of PMN under anaerobic conditions. It is not known whether PMN are able to migrate and release the contents of their granules in the presence of sulfide. PMN were exposed to various levels of sulfide and their chemotaxis and degranulation were studied when they were stimulated with N-formyl-methionyl-leucyl-phenylalanine or zymosan-activated serum. Chemotaxis was evaluated with the agarose method. The release of granule markers, lactoferrin and myeloperoxidase, was evaluated with enzyme-linked immunosorbent assay. PMN had similar capacity for chemotaxis under aerobic and anaerobic conditions. The migration of PMN was only to a minor extent inhibited by 1-2 mM sulfide. The release of lactoferrin and myeloperoxidase was the same under aerobic and anaerobic conditions and was not significantly influenced by sulfide. PMN seem to be very well suited to defend the tissue against bacteria under the harsh conditions prevailing in the periodontal pocket.

Anaerobiosis↗

The relationships between seasonal variations in the concentration of urea in bulk milk and the production and fertility of dairy herds.

The concentration of urea was measured in bulk milk samples taken on seven occasions during a period of 13 months from 1,658-1,815 of the 2,100 suppliers of milk to a dairy. The mean concentration of urea was significantly higher when the cows were grazing than when they were housed, but there were no significant variations within either of these periods. In herds with very low milk urea concentrations while they were housed (< 2.4 mmol/l) the mean increase during the grazing season was approximately 2.0 mmol/l, whereas in herds with very high urea concentrations while they were housed (> 6.0 mmol/l) there was a slight decrease in urea concentration during the grazing season. The annual milk yield of herds with low urea concentrations was significantly lower than the yield of herds with intermediate or high concentrations. The interval between calving and first insemination was significantly longer in herds with low milk urea concentrations, but these herds also had a higher 56-day non-return rate.

Animals↗