Caloric restriction reduces proteinuria in male rats with established nephropathy.

Reducing proteinuria is a crucial approach in preventing kidney function loss. Previous preclinical studies indicated that caloric restriction (CR) imposed at a young age protects against age-related proteinuria. However, these studies have not explored CR in established renal disease. Therefore, this study aimed to investigate the impact of CR on established proteinuria. Rats, aged 12 ± 2 weeks, were administered 2.1 mg/kg of Adriamycin. Six weeks after injection, protein excretion was measured, and a [13 N]ammonia positron emission tomography (PET) scan was conducted to assess kidney perfusion. After 7 weeks rats were divided into four groups: ad libitum (AL) and CR groups fed either a 12% or a 20% protein diet. All groups were treated for 12 weeks. Blood pressure was measured and a second PET scan was acquired at the end of the study. The animals subjected to CR exhibited a 20.3% decrease in protein excretion (p = 0.003) compared to those in the AL groups. Additionally, blood pressure in the CR group was 21.2% lower (p < 0.001) than in the AL groups. While kidney function declined over time in all groups, the 20% CR group demonstrated the smallest decline. Thus CR effectively reduces urinary protein excretion and lowers blood pressure in rats with established proteinuria.

On the pathogenesis of abortion in acute nitrite toxicosis of pregnant dairy cows.

Six cows, 220 to 260 d pregnant, were used to study possible abortifacient effects of absorbed nitrite. Maternal and fetal bloodvessels were catheterized. Nitrite was infused intravenously (i.v.) for 30 minutes on Days 1, 3 and 5, commencing at least 5 d postcatheteration. The dose used was 7, 9.5 and 12 mg NO(2)(-)/kg bodyweight, respectively. Nitrite caused a dose-related (P < 0.05) conversion of maternal hemoglobin (Hb) into methemoglobin (MHb); a 30 to 50% decrease of mean arterial bloodpressure; an increase in heart rate, with dose-related recovery periods; and a decrease in partial oxygen tension (PO(2)) of maternal blood. Maternal partial carbon dioxide tension (PCO(2)), pH and electromyographic activity of the uterus were unchanged. Fetal changes included a small increase in MHb content, variable changes in heart rate (tachycardia and bradycardia), and decreases in fetal PO(2), with considerable differences between animals. All calves were born alive. Three cows calved early, 2 to 3 d after the highest nitrite dose. The hematological and cardiovascular data suggest that these three fetuses experienced a more serious hypoxemic stress than the other fetuses.

Effects of an inadequate dietary intake of magnesium on osteogenesis in dairy cows during the dry period.

The osteogenic activity in the rib bones of 33 dairy cows (14 of parity 1 or 2, and 19 of parity 3 or more) during their last two months of pregnancy, and the effects upon it of a deficient supply of dietary magnesium, were studied by means of intravenous infusions of the fluorochromes oxytetracycline hydrochloride, calcein and chlortetracycline given nine weeks, five weeks and one week, respectively, before the expected time of parturition. Seven weeks before this date the cows' ration was changed to one containing either 0.22 per cent magnesium (LMg) or 0.82 per cent magnesium (HMg) in the dry matter, and the potassium content of both rations was increased to approximately 4.1 per cent in the dry matter to reduce the absorption of magnesium. Four of the 10 LMg-high parity cows showed signs of periparturient hypocalcaemia. A significant decrease in the number of labelled osteons towards parturition was demonstrated in both the low parity (P less than 0.05) and high parity cows (P less than 0.001). The mean bone apposition rate in high parity cows was significantly lower (P less than 0.001) than in low parity cows. The different levels of magnesium in the diets of the cows had no significant effects on the numbers of osteons which were labelled nine weeks, five weeks or one week before parturition, or on the numbers of osteons which took more than one label or on the bone apposition rate. These results show that in these cows the rate of bone remodelling decreased as parturition approached.

Effects of reducing dietary ([Na+ + K+]-[Cl- + SO4 =]) on bone in dairy cows at parturition.

The effects of feeding diets with different milliequivalents (mEq) of dietary ([Na+ + K+]-[Cl- + SO4 =]) to dairy cows during the last seven weeks of pregnancy on bone morphology at parturition were studied. Nine monozygotic twin pairs of pregnant cows (five pairs of parity 1 or 2 and four pairs of parity 3 or more) were allocated to two diets which were formulated to provide either -4 mEq (anion diet) or +572.5 mEq (cation diet) of ([Na+ + K+]-[Cl- + SO4 =]) kg-1 dietary dry matter. Bone biopsies were taken from the tuber coxae between three and eight hours after parturition. The plasma concentrations of calcium and inorganic phosphorus, the total plasma alkaline phosphatase activity and the urinary hydroxyproline:creatinine ratio were not significantly affected by diet during the experimental period. In low parity (2 or less) cows the percentage trabecular bone volume, the percentage osteoclast surface and the mean number of osteoclasts per microscopic field (identified by Goldner staining) were lower on the anion diet than on the cation diet (P < 0.02). In the high parity cows, the percentage osteoid volume (P < 0.05) and the ratio of percentage osteoid volume to percentage osteoid surface (P < 0.001) were greater in the cows fed the anion diet than in the cows fed the cation diet. The results show that reducing the mEq of dietary ([Na+ + K+]-[Cl- + SO4 =]) to -4 mEq kg-1 dietary dry matter affected some of the parameters of bone formation but did not enhance bone resorption.

Effects of calcium and magnesium intakes and feeding level during the dry period on bone resorption in dairy cows at parturition.

A study was made of the influence of low and high calcium intakes at two feeding levels (experiments 1 and 2), and of different magnesium intakes (experiment 3) during the dry period, on the cellular resorptive activity in bone of dairy cows at parturition. In experiment 1 (26 cows) the feed intake was 1.12 times maintenance and the calcium intake was either 13.0 g d-1 or 83.5 g d-1. In experiment 2 (33 cows) the feed intake was 1.9 times maintenance and the calcium intake was either 26.4 g d-1 or 87.2 g d-1. In experiment 3 the cows feed intake was 1.4 times maintenance, the calcium intake was 71 to 72 g d-1 and the magnesium intake was either 16.6 g d-1 or 71.0 g d-1. Bone biopsies were taken from the tuber coxae between three and eight hours after parturition. In experiment 1 the cellular resorptive activity in bone from older cows was higher in the cows receiving the low calcium diet. In experiment 2 the differences between the bone resorptive activities of the two groups were small. In experiment 3 the bone resorptive activity was lower in the cows with a deficient supply of magnesium. There were significant relationships in young cows, but not in older cows, between the cellular resorptive activity in bone and the rate of calcium mobilisation measured biochemically. These results suggest that in older dairy cows bone resorption makes only a minor contribution to the total rate of calcium mobilisation at parturition and is therefore of minor importance for the prevention of periparturient hypocalcaemia.

Influence of a deficient supply of magnesium during the dry period on the rate of calcium mobilisation by dairy cows at parturition.

The influence of a deficient magnesium supply during the dry period on the ability of dairy cows to mobilise calcium at parturition was investigated. The daily rations pre-partum consisted of 6 kg grass hay, and 4 kg concentrates containing either 1.58 per cent magnesium (HMg) or 0.22 per cent magnesium (LMg). Nine cows of parity one to six received the LMg diet and 10 cows of parity one to seven the HMg diet. Both rations provided 1.40 times maintenance on an energy basis and contained 4 per cent potassium in the dry matter. Throughout the dry period the mean concentration of magnesium in the plasma of the LMg group was significantly lower than in the HMg group and at parturition the mean plasma concentrations were 0.65 mmol litre-1 and 1.16 mmol litre-1, respectively. After parturition two cows in the LMg group showed clinical signs of hypocalcaemia but none of the HMg group did so. Cows of the LMg group had a lower mean rate of calcium mobilisation (0.27 mmol min-1) than those of the HMg group (0.34 mmol min-1) but the difference could not be explained by differences in bone turnover as reflected by urinary hydroxyproline excretion. Such a reduced rate of calcium mobilisation may be a contributory factor in the high incidence of milk fever in some herds fed inadequate magnesium in the dry period.

Effects of reducing dietary [(Na+ + K+) - (Cl- + SO4=)] on the rate of calcium mobilisation by dairy cows at parturition.

The effects of feeding diets with different milliequivalents (meq) of dietary [(Na+ + K+) - (Cl- + SO4=)] to dairy cows during the last seven weeks of pregnancy on their acid-base status and calcium mobilisation rate around parturition were studied. Ten monozygotic twin pairs of pregnant cows (five pairs of parity 1 or 2, and five pairs of parity 3 or more) were allocated to two diets which were formulated to provide either -4 meq (anion diet) or +572.5 meq (cation diet) of [(Na+ + K+) - (Cl- + SO4=)] kg-1 dietary dry matter (DM). The daily rations consisted of 4 kg grass hay and 7 kg concentrates. Changes in meq of dietary [(Na+ + K+) - (Cl- + SO4=)] were achieved by adding KCl, K2SO4 and (NH4)2SO4 (anion diet) or K2CO3 (cation diet) to basal concentrates. Plasma calcium concentration and blood acid-base parameters were not affected by dietary treatment. However, urinary calcium excretion was markedly higher and urinary pH and bicarbonate excretion significantly lower in cows fed the anion diet than in cows fed the cation diet. The responses to hypocalcaemia induced by an intravenous infusion of EDTA solution were similar in the cows fed either diet.

An analysis of the buffer system in the rumen of dairy cattle.

A method is presented for the analysis of buffer systems in the rumen using the first derivation of titration curves. Bicarbonate and volatile fatty acids (VFA) are the main components of the buffering system in the rumen fluid of dairy cattle under widely different feeding conditions. Phosphate from saliva is of little importance as a buffer, but neutralizes acids produced in the rumen. After studying five cows during the peripartal period a spontaneous and transient increase in the concentrations of VFA and a soluble marker (PEG) as well as a drop in pH and in the bicarbonate concentrations not related to feeding was observed in two animals that were sampled several hours before parturition. The potential risk of provoking rumen disturbances upon feeding animals close to the time of parturition, when buffering capacity may be minimal, is stressed.

Effects of a deficient magnesium supply during the dry period on bone turnover of dairy cows at parturition.

The bone activity and bone mineral content in rib bones resected from 33 dairy cows between 3 and 8 h after parturition were measured, and the effects upon them of a deficient supply of dietary magnesium (Mg) during the last seven weeks of pregnancy were studied. The cows were fed a diet containing either 0.22% magnesium (low Mg) or 0.82% magnesium (high Mg) in the dry matter (DM), and the potassium content of both rations was increased to approximately 4.1% in the DM to reduce the absorption of magnesium. In the cows fed the low-Mg diet a fall in plasma Mg concentration was observed. In the low-Mg, low-parity cows the plasma Mg concentrations at parturition were higher than in the low-Mg, high-parity cows, i.e. 0.83 mmol/l and 0.54 mmol/l, respectively. After parturition four cows in the low-Mg, high-parity group showed clinical signs of hypocalcaemia but none of the other groups did so. The bone formation in low-parity cows was significantly (P less than 0.05) affected by Mg supply, with higher percentages of both trabecular surface covered by osteoid and osteoid volume in the low-Mg group. In the high-parity cows no significant differences in bone formation were found between the low- and high-Mg groups. An inadequate Mg supply resulted in a significantly (P less than 0.05) higher Ca content in the bone ash of low-parity cows and a significantly (P less than 0.05) higher bone ash percentage in the bone of high-parity cows.

Effects of low and high calcium intake prepartum on calcium mobilization rate around parturition in dairy cows.

Forty-one dairy cows were fed a low (LCa-13 g/d) and a high (HCa-83.5 g/d) calcium ration in the 8 weeks prior to parturition and the effect on the Ca mobilization rate around parturition was studied. Plasma Ca values were stable in the LCa group around parturition. In the older cows of the HCa group a very slight decrease in the mean plasma Ca was observed: 2.58 mmol/l at 12-36 h ante partum decreased to 2.38 mmol/l at parturition. Hypocalcaemia, which commonly occurs around parturition, did not occur in 40 of the cows. A subclinical hypocalcaemia (1.8 mmol/l) occurred in one cow (parity 10) from the HCa group. To assess the efficiency of Ca mobilization, a severe hypocalcaemia (1.0 mmol/l) with clinical signs was induced by means of Na2EDTA infusion (0.90 mmol/min), starting at 10 h post-partum. The older cows in the LCa group required more Na2EDTA than those in the HCa group. Higher urinary hydroxyproline excretion in the week before parturition in the LCa than in the HCa group suggested a higher bone turnover. Plasma PTH levels around parturition were not significantly different between the groups. The amount of colostrum milked out in the first 10 h post-partum did not influence Ca homeostasis around parturition. The results contradict those of many other experiments in which hypocalcaemia was observed in cows ingesting high levels of Ca. It is concluded that the restricted feed intake prepartum possibly had a favourable effect on Ca homeostasis.

Influence of prepartum calcium intake on calcium mobilization rate around parturition in dairy cows fed at a high prepartum feeding level.

The influence of a low and a high prepartum calcium (Ca) intake on Ca mobilization rate around parturition was studied in 44 dairy cows fed a ration sufficient for 1.90 times maintenance requirements during the dry period. The plasma Ca level declined on the day of parturition in the group fed the low Ca intake (LCa: 26.4 g/d) as well as in the group fed the high Ca intake (HCa: 87.2 g/d). Plasma Ca levels of the HCa group were lower at parturition, and in this group 1 cow had milk fever after parturition. In the HCa group 6 cows had a plasma Ca level less than or equal to 2.0 mmol/l at parturition and/or 10 h post-partum (pp), versus 1 cow in the LCa group. Na2EDTA was intravenously infused at 10 h pp to induce hypocalcaemia to a level of plasma Ca not bound to EDTA of approximately 1.0 mmol/l. The LCa groups tended to require more Na2EDTA than the HCa groups, however the difference was significant only in the younger cows. After the Na2EDTA infusion 7 cows of the HCa group and 1 of the LCa group did not recover spontaneously and needed to be treated. The mean plasma PTH levels of the LCa group ante-partum were slightly higher than those of the HCa group. The Ca level of the prepartum ration did not influence urinary hydroxyproline excretion, which suggests that the Ca intake of 26.4 g/d was too high to stimulate bone turnover. Comparison of the present results with those of an earlier experiment in which the prepartum Ca intake at a low feeding level (1.12 times maintenance) was studied, led to the conclusion that higher prepartum feed intake has a clear negative influence on Ca homeostasis around parturition.

Time courses of plasma magnesium concentrations and urinary magnesium excretion in cows subjected to acute changes in potassium intake.

Hypomagnesaemic tetany in cows develops occasionally after an acute increase in K intake such as can occur when cows are transferred to spring grass. There is evidence that under these conditions plasma Mg concentrations are only transiently decreased. In this study the questions addressed were whether the plasma Mg concentration, indeed adapts to a high K intake as only dietary variable, and whether urinary Mg excretion is associated with this adaptation. Dry cows were fed rations containing either 26 or 50 g K/kg dm, the extra K being in the form of KHCO3. When the cows were acutely transferred from the low to the high K ration, plasma Mg concentrations fell slightly, but significantly from 0.86 to 0.76 mmol/l within five days, but rose again to 0.80 mmol/l after another 23 days, this rise being also statistically significant. None of the animals developed tetany. The decrease in plasma Mg concentration in individual animals after five days on the high-K ration ranged from 6 to 21%. The time course of urinary Mg excretion resembled that of plasma Mg concentration; minimum Mg excretion was seen after four to six days on the high-K ration with a subsequent increase thereafter. To explain the transient lowering of plasma Mg concentration, it is suggested that the K-induced decrease in Mg status caused a delayed increase in the carrier-mediated component of Mg absorption, which in turn caused an increase in urinary Mg excretion. When the cows were acutely switched from the high to the low K ration, plasma Mg concentration and urinary Mg excretion rose, but no transient changes were seen.

Substitution of dietary calcium chloride for calcium carbonate reduces urinary ph and urinary phosphorus excretion in adult cats.

In a 4x4-wk cross-over study, eight adult cats were given four moist diets containing identical amounts of calcium (13.9 mmol/MJ) but with different ratios of calcium carbonate to calcium chloride, the calcium salts providing half of the total dietary calcium. Increasing amounts of calcium chloride were substituted for equimolar amounts of calcium carbonate. Higher intakes of calcium chloride caused significantly lower pH values in postprandial and 24-h urine samples. The urinary excretion of ammonium and titratable acid rose with increasing calcium chloride intake. The urinary concentrations of calcium and magnesium were not affected by the type of calcium salt, but the urinary excretion and concentration of phosphorus were significantly depressed when the amount of calcium chloride in the diet was increased. The results are discussed in the context of dietary prevention of and therapy for struvite urolithiasis in cats.

Nitrate poisoning in cattle.

Summary In a series of experiments the effect of administering KNO(2) was studied, during parturition, on the capability of oxygen transport of maternal blood and on oxygen transfer to foetal blood. The following blood parameters were analysed, MHb percentage, pO(2), O(2)-saturation, pH, pCO(2), and (NO(2)) in maternal arterial blood (carotid art.) and venous blood (jugular vein) and in foetal arterial blood (umbilical art.) and venous blood (umbilical vein). The relative O(2)-saturation was calculated from the estimated O(2)-saturation by multiplying with the factor Hb (mmol/1) minus MHb (mmol/1), divided by Hb (mmol/1). In addition, blood pressure in the carotid artery, heart rate, and respiration rate in the dam were continuously recorded for some hours. A dosage of 9 to 12 mg of NO(2)/kg body weight intravenously or of 30 mg of NO(2)/kg body weight orally to the dam caused much higher MHb percentages and NO(2) contents in the maternal blood than in the foetal blood. In maternal blood the ratio of NO(2) content td MHb percentage was proportional to that in foetal blood. In the arterial blood, MHb percentages were almost as high as in the venous blood. After administering of nitrite, relative O(2)-saturation dropped simultaneously with the increase in methaemoglobin. Nitrite treatment caused a drop in the maternal blood pressure; heart rate and respiration rate increased. O(2)-saturation in the blood in the umbilical vein was much lower in the animals with nitrite treatment than in those without. These experimental results show clearly that the oxygen capacity of the blood decreases after nitrite treatment. In pregnant cows the oxygen supply to the foetus will be adversely affected after nitrate intake, especially by the lower oxygen transfer via the placenta, though hardly at all by methaemoglobin formation in the foetal blood. When the oxygen transfer to the foetal blood decreases too sharply, intra-uterine death and ultimately abortion may result.

Liver triacylglycerol concentrations around parturition in goats with either pre-partum restricted or free access to feed.

The hypothesis was tested that goats allowed ad libitum access to feed during the dry period develop higher post partum hepatic triacylglycerol concentrations than do goats given a restricted amount of feed during the dry period. Goats in their second or more pregnancies were either given a restricted amount of hay, maize silage and concentrate (n = 5) or had free access to this feed mixture while the composition was kept constant (n = 11). After parturition both groups were allowed ad libitum access to feed. Post partum liver triacylglycerol concentrations, as measured in liver biopsies, were significantly raised in goats allowed ad libitum access to feed during the dry period. The increase in liver triacylglycerols was associated with slightly higher plasma concentrations of non-esterified fatty acids but lower serum 3-hydroxybutyrate concentrations. The feeding regimen during the dry period did not significantly influence post partum liver glycogen concentrations and serum levels of glucose, cholesterol, and insulin. The increase in post partum liver triacylglycerol concentrations in the goats allowed ad libitum access to feed instead of a restricted ration during the dry period, was associated with a significant rise in serum alkaline phosphatase activities, whereas other liver function and cell damage indicators in serum, i.e. aspartate aminotransferase, lactate dehydrogenase, gamma glutamyl transpeptidase, and bilirubin, were unchanged. Feed intake after parturition tended to be higher in the goats allowed ad libitum access to feed during the dry period but milk production was significantly raised.(ABSTRACT TRUNCATED AT 250 WORDS)

Microbial and nutritional aspects of feeding fermented feed (poultry by-products) to pigs.

Broiler by-products (heads, feet, and viscera) mixed with 4% dextrose were pasteurized for 4 min at 90 degrees C core temperature, cooled to 20 degrees C, and fermented with Lactobacillus plantarum as starter culture. These fermented poultry by-products were fed to 12 individually housed fattening pigs as part (17.6% of the dry matter) of their fattening ration, the remainder composed of compound pig feed. Control pigs received a compound pig feed only. Both groups of pigs were fed restrictively on the basis of body weight. The technical results of the pigs fed the experimental diet showed a significantly improved feed:gain ratio (2.46 vs 2.57), a significantly higher carcass weight (86.1 vs 81.8 kg), a lower meat percentage (50.9 vs 52.5%) and an increased backfat thickness (21.5 vs 18.7%). The bacterial flora in the intestinal tract of the pigs fed the experimental diet differed significantly from the control animals. Decreased colony counts of mesophilic aerobic bacteria, Enterobacteriaceae, enterococci and lactobacilli were found in the rectal content and the prevalence of salmonella was lower. It is suggested that the improved feed:gain ratio and the reduced bacterial activity of the measured groups of bacteria is a result of 1) the higher energy content of the diet, and(or) 2) an assumed enhanced digestibility of nutritional components in the diet, and(or) 3) the lower incidence of diarrhea in the pigs fed with fermented poultry by-products. This resulted in a lower contamination level of enteropathogenic bacteria like, salmonella and Escherichia coli, in the gastro-intestinal tract of the pigs fed fermented poultry by-products.

Study of osteogenesis in adult sheep on a high and a low calcium ration by means of fluorescing bone markers.

The rate of osteogenesis was studied in 8 non-pregnant, non-lactating Friesian dairy sheep, 3-6 years old, by means of a treatment with 3 different bone seeking agents. Four sheep were fed a low calcium ration (LCa:1.8 g Ca/d) and four other sheep a high calcium ration (HCa:12.7 g Ca/d). The bone markers, oxytetracycline-HCl, alizarine-complexion and demeclocycline-HCl, were administered at intervals of 6 weeks, and the sheep were killed 1 week after administration of the last marker. In undecalcified cross sections from the middle of ribs 2, 10 and 12, and from the proximal and distal parts of rib 10, the numbers of labelled osteons and the number of osteons with 1, 2 or 3 markers were counted under fluorescent microscopy. In the ribs of sheep from the LCa group, the number of labelled osteons and the quantity of labels per osteon tended to be higher than those of sheep from the HCa group. When osteogenic activity was compared in the different sites of ribs analysed, lowest osteogenic activity was observed in the proximal part of the 10th rib. The use of fluorescing markers offers the possibility of studying osteogenic activity over a certain period of time in adult sheep.

[Animal nutrition in veterinary science]. / Diervoeding in de diergeneeskunde.

In the past, emphasis was on deficiencies in relation to nutrition and animal health, but nowadays it is more on the relevance of nutrition (or nutrients) to the aetiology and prevention of disease. This is illustrated by an outline of the association between the (over)feeding of dairy cattle before and around calving and the incidence of diseases that frequently occur post calving. The nutritional management of clinical diseases and the application of enteral or tube feeding is nowadays part of modern pet animal practice. The difference between a nutrient and a medicine is becoming vague and the application of recombinant DNA-technics offers new and interesting possibilities to increase the medicinal value of certain feeds. These trends in animal health care together with the wish of clients to be informed of the feeding of their animals, either pet animal of farm animal, greatly increase the demand for knowledge and skill of animal nutrition. The current veterinary medicine curriculum does not allow sufficient time for students to gain the necessary knowledge and skill in animal nutrition. Therefore specialists in veterinary nutrition are needed who can advice the providers of veterinary nutritional and other health care services in order to use optimal the nutritional support possibilities in animal health care as well as in improving productivity.

[A comparative study of the in-vitro solubility and availability of magnesium from various sources for cattle]. / Een vergelijkend onderzoek naar de in vitro oplosbaarheid en de beschikbaarheid van magnesium uit verschillende magnesiumbronnen voor het rund.

Magnesium (Mg) is often added to the feed of cattle to meet the dietary requirements of this element. Magnesium oxide (MgO) is usually used. However, if the supplemented MgO does not dissolve in the rumen, it will not be effective. The solubility of eight preparations of MgO was measured with three different in vitro methods. Particle size and origin varied among the eight preparations. Solubility in vitro ranged from hardly soluble (MgO-C) to highly soluble (MgO-A). In an experiment with four cows with rumen fistulas (4 x 4), the solubility of the MgO preparations in vitro was found to parallel their solubility in the rumen and their urinary excretion. It was concluded that not only the amount of MgO added to the ration is important but also the solubility of the MgO.

[Skeletal development in the dog in relation to nutrition]. / Skeletontwikkeling bij de hond in relatie tot de voeding.

Growth hormone (GH) and insulin-like growth factor I (IGF-I) play important roles during growth, including effects on enchondral ossification. GH plasma concentration is strongly influenced by the nutritional status of the dog. Fasting induces a non-responsiveness of the liver to GH, leading to a decrease in IGF-I release by the liver and a delay in growth. Overfeeding leads to abnormal skeletal development, i.e., osteochondrosis and hip dysplasia. Subnormal plasma concentrations of sex hormones lead to a delay in physiologic epiphysiodesis, whereas high levels of sex steroids may induce premature physeal closure. Dietary calcium, phosphorus, and vitamin D are important factors in the process of enchondral ossification. If these nutrients are inadequate, imbalanced, or oversupplemented, skeletal development in young growing dogs can be disturbed, leading tot severe pathologic changes. Energy requirements decrease gradually during the first year of life and unrestricted feeding can easily lead to pups being overweight. The protein requirements are strongly influenced by the quality and digestibility of protein sources in the food. In dog foods 12-14 g protein/1000 kJ appears to be adequate for growth. It is likely that the two most commonly made mistakes in dog nutrition in the Netherlands, are oversupplementation with energy and/or calcium. Restricted feeding is advised during growth and no food-additives are required when commercially prepared complete dog foods are used.