Alkaline phosphatase adults

Domestic sheep (Ovis aries) fed a low-zinc diet (2.2 mg Zn/kg DW diet) for 50 days, when compared to those fed a zinc-adequate diet (33 mg Zn/kg DW diet), excreted less zinc (<4 mg daily vs. 23 to 25), consumed less food (409 g daily vs. 898), and had lower plasma zinc concentrations (0.18 mg/L vs. 0.53 to 0.58) a reduction in plasma alkaline phosphatase activity and an increase in plasma zinc binding capacity were also noted (Khandaker and Telfer 1990). Sensitive indicators of zinc deficiency in lambs include significant reductions in plasma alkaline phosphatase activity and plasma zinc concentrations signs were clearly evident in lambs fed 10.8 mg Zn/kg DW diet for 50 to 180 days (Vergnes et al. 1990). A normal diet for lambs contains 124 to 130 mg Zn/kg DW ration vs. 33 for adults (Vergnes et al. 1990). One recommended treatment for zinc-deficient sheep is ruminal insertion of zinc-containing boluses every 40 days bolus zinc release is about 107 mg daily (Khandaker and Telfer 1990). 

Teriparatide is contraindicated in patients at baseline increased risk for osteosarcoma (e.g., Paget s bone disease, unexplained alkaline phosphatase elevations, pediatric patients, young adults with open epiphyses, or patients with prior radiation therapy involving the skeleton). 

Condensed (poly) phosphates may exert different effects on calcium utilization than the aforementioned effects of simple (ortho-) phosphates. Polyphosphates have a much greater affinity for calcium than do orthophosphates, and soluble calcium-polyphosphate complexes are readily formed in the gastric and intestinal environments. In addition, polyphosphates must be hydrolyzed by an intestinal alkaline phosphatase (27) prior to absorption. We have found polyphosphates to be incompletely (80.5%) hydrolyzed to orthophosphate during the digestive process in young adult males when calcium intake was low only 56% of a 1 g phosphorus supplement was absorbed from a polyphosphate sources as compared to 71% from an orthophosphate source (5). 

In a recent study 1 of over 600 children and adults from birth to 27 years of age, Clark and Beck found that the levels for each individual are characteristic and tend to remain about the same year after year. They conclude that "a single sampling every year would, generally speaking, be sufficient to classify a child regarding plasma alkaline phosphatase activity." The over-all range in the tabulated data... 

PHARMACOLOGICAL ACTIVITIES AND CLINICAL TRIALS Alkaline phosphatase stimulation. Extract of the leaf, administered orally to adults, was active. Patients with subacute hepatic necrosis had negative workup, except for consumption of 15 tablets of the herbal extract per day for 4 months L Anthelmintic activity. Water and petroleum ether extracts of the dried oleoresin were active on Eimeria tenella in chicken - . Anti-amoebic activity. The resin of Larrea produced inhibitory activity at a concentration of 1 ppm on Entamoeba invadens PZ axenic cultures. The nordihydroguaiaretic acid activity was observed at 10" to 10" concentrations - . 

As a brief introductory summary, vitamin D substances perform the following fundamental physiological functions (1) promote normal growth (via bone growth) (2) enhance calcium and phosphorus absorption from the intestine (3) serve to prevent rickets (4) increase tubular phosphorus reabsorpiion (5) increase citrate blood levels (6) maintain and activate alkaline phosphatase m bone (7) maintain serum calcium and phosphorus levels. A deficiency of D substances may be manifested in the form of rickets, osteomalacia, and hypoparathyroidism. Vitamin D substances are required by vertebrates, who synthesize these substances in the skin when under ultraviolet radiation, Animals requiring exogenous sources include infant vertebrates and deficient adult vertebrates, Included there are vitamin D (calciferol ergocalciferol) and vitamin D< (activated 7-dehydrocholesterol cholecalciferol). 

The plasma concentration of calcidiol is the most sensitive and usefiil index of vitamin D status, and is correlated with elevated plasma parathyroid hormone and alkaline phosphatase activity (Table 3.4). As shown in Table 3.2, the reference range of plasma calcidiol is between 20 to 150 nmol per L, with a twofold seasonal variation in temperate regions. Concentrations below 20 nmol per L are considered to indicate impending deficiency, and osteomalacia is seen in adults when plasma calcidiol falls below 10 nmol per L. In children, clinical signs of rickets are seen when plasma calcidiol faUs below 20 nmol per L. The plasma concentration of calcitriol does not give a useful indication of vitamin D status. The reference range is between 38 to 144 pmol per L and is maintained because of the stimulation of calcidiol 1-hydroxylation by parathyroid hormone secreted in response to faUing concentrations of calcium (Holick, 1990). 

Another metabolic disorder that is hereditary and little known is hypophosphatasia. Hypophosphatasia is an inherited metabolic (chemical) bone disease that results from low levels of an enzyme called alkaline phosphatase (ALP). ALP is normally present in large amounts in bones and the liver. In hypophosphatasia, abnormalities in the gene that makes ALP lead to the production of inactive ALP. Subsequently, several chemicals, including phosphoethanolamine, pyridoxal 57-phosphate (a form of vitamin B ) and inorganic pyrophosphate, accumulate in the body and are found in large amounts in the blood and urine. It appears that the accumulation of inorganic pyrophosphate is the cause of the characteristic defective calcification of bones seen in infants and children (rickets) and in adults (osteomalacia). 

In 1950 Seligman and his co-workers (S13) suggested the use of sodium j8-naphthyl phosphate as a substrate for the determination of acid or alkaline phosphatase activity. For the former, 1 ml of 1 20 diluted serum was added to 5 ml of 0.4 mM sodium 8-naphthyl phosphate in 0.1 M acetate buffer of pH 4.8, and the reaction was allowed to proceed for 2 hours at 37.5°C. The addition of 4 drops of IM sodium carbonate solution served to retard the reaction as well as to raise the pH to the optimal level for coupling with 1 ml of a solution of tetrazotized ortho-dianisidine. After 3 minutes, the protein was precipitated with trichloroacetic acid, the dye extracted with ethyl acetate, and the color density determined in the region of 540 nm. The unit of phosphatase activity was defined as that amount of enzyme which liberates the color equivalent of 10 ml of j8-naphthol per hour at 37.5° in 1 hour. The serum acid phosphatase in a group of normal adults ranged from 0.7 to 1.6 units and averaged 1.0 unit per 100 ml of serum. 

Cholestasis has been reported in infants treated with amphotericin for systemic Candida infections (SEDA-14, 230). Most of the above reports were incidental, and amphotericin cannot be regarded as a known cause of liver damage. This does not necessarily also apply to liposomal amphotericin and other lipid formulations. Therapy with L-Amb, AmBisome was associated with a rise in alkaline phosphatase in over a third of children treated with AmBisome (93) and with hepatic dysfunction in a little under 20% of adolescents and adults. In a small retrospective study, ABLC was withdrawn in 27% of patients because of rises in serum bilirubin and alkaline phosphatase, a finding confirmed in a larger prospective study. Cholestasis has also been observed with ABCD, in contrast to reports that L-AmB does not increase transaminases (5). 

Alkaline phosphatase may arise from liver, bone, or placenta. The alkaline phosphatase in the sera of normal adults comes primarily from the liver or biliary tract. Elevated levels of alkaline phosphatase are seen in primary or secondary liver... 

Figure 47-18 Algorithm for using elevated activities of serum alkaline phosphatase in the diagnosis of liver disease in adults.

It is a fact that, in a normal adult healthy individual, the serum alkaline phosphatase remains relatively constant. This event is indistinguishable from the constancy of other serum proteins such as albumin, glycoproteins, etc. Therefore the considerations that apply to the homeostasis of serum proteins logically apply to serum enzymes. These have been discussed elsewhere (F5). 

Views on the Nature op Serum Alkaline Phosphatase in Normal Adult Subjects... 

Therefore, we are adopting as a working hypothesis that the main origin of serum alkaline phosphatase is the intestinal mucosa in nonpregnant normal adults. This hypothesis requires only one assumption, namely, that the intestinal alkaline phosphatase undergoes alteration in vivo to forms indistinguishable from the alkaline phosphatases in liver and bone preparations. The hypothesis enables one to interpret the biochemical and starch-gel data in a fashion that admits the fewest assumptions. 

D12. Dent, C. E., and Harper, C. M., Plasma alkaline phosphatase in normal adults and in patients with primary hyperparathyroidism. Lancet I, 559 (1962). 

Adult male COBS CD (SD)BR rats given 885 mg/kg/day 2-butoxyethanol for 6 weeks showed increased relative, but not absolute, liver weight in all dose groups ( 222 mg/kg/day) (Eastman Kodak 1983 Krasavage 1986). Histological examination of livers revealed hemosiderin deposition in the liver at 443 mg/kg/day and hepatocytomegaly at 885 mg/kg/day. Statistically significant increases were found for serum alkaline phosphatase at 443 mg/kg/day and for serum alanine aminotransferase at 885 mg/kg/day. 

Table 3 shows the range of alkaline phosphatase activities in neonatal cord blood or peripheral blood as reported in a number of publications. In most of these reports, the mean values of neonates were higher than those of adult reference groups. However, some workers obtained mean values lower than those of adults. Kitchener et al. (K22) speculated that these relatively low activities may have been due to the use of citrated plasma. 

Some dramatic rises and subsequent falls in serum alkaline phosphatase have been described between the ninth and fifteenth years of life (F13, S27). Pettifor et al. (P12), who studied a group of black children, found no such rises, but in other series, values up to 7 times the upper reference limit for adults were present during a rapid growth spurt (F13). 

A steady decline in serum alkaline phosphatase activity toward adult values is seen in late adolescents of both sexes (Fig. 3). This process begins at approximately 11 years of age in females (F13), so that by the time they reach their twentieth year, their levels are almost indistinguishable from those of older females. In males, the decline toward adult values commences later and is more prolonged, so that levels do not merge into those of older adult males until well into the third decade (C22, F13, K23, K33). 

Fig. 2. Plasma alkaline phosphatase values in children and adolescents plotted as moving geometric means. Each mean is based on data from 80 children. The next mean is based on data from the 30 oldest of these 80, plus the next 50 in order of age. The solid circles denote males, the open circles females. The upper reference limit for adults obtained by the method employed was 256 U/liter. Note that the peripubertal rise occurs later in boys and is more pronounced than in girls. From Fleisher et al. (F13) with permission.

---