Decreased Serum Alkaline Phosphatase Activity Research Articles

Effect of Zinc-Deficient Diet on Two Strains of Mice.

Zinc (Zn) deficiency is one of the most common nutritional deficiencies worldwide. It is associated with reduced nutritional status and has been reported in cases of growth retardation, alopecia, and decreased serum alkaline phosphatase (ALP). It has also been reported to occur during total parenteral nutrition (TPN) administration and is associated with various diseases, such as liver diseases, diabetes, and kidney disease. We used Zn-deficient mice of ICR and C57BL/6J strains to investigate the various effects of Zn deficiency on the body, assuming that a healthy person may also become deficient in Zn either due to an unbalanced diet or malabsorption. The results showed that a Zn-deficient diet suppressed body weight gain and increased the tissue weight of the kidneys and cecum in both strains of mice. Biochemical data showed no decrease in serum ALP activity in either strain. Furthermore, in C57BL/6J mice, a Zn-deficient diet caused alopecia, loss of villi in the small intestine, and eventually affected the intestinal mucosa, which could be a risk factor for poor nutritional status. Although previous reports have shown that serum ALP activity is decreased during Zn deficiency, this is the first study that used 4-wk-old mice of ICR and C57BL/6J strains to show that serum ALP activity, which is a Zn deficiency marker, did not decrease in the two strains of Zn-deficient mice; furthermore, a Zn-deficient diet causes various symptoms.

The ameliorative efficacy of Thymus vulgaris essential oil against Escherichia coli O157:H7-induced hematological alterations, hepatorenal dysfunction and immune-inflammatory disturbances in experimentally infected rats.

The purpose of the present study was to evaluate the possible ameliorative role of Thymus vulgaris (T. vulgaris) essential oil against Escherichia coli O157:H7 (E. coli O157:H7) deleterious effects in both blood and different tissues of rats by assessing the hematological, biochemical and immune-inflammatory parameters besides the histopathological alterations in the different organs. Forty male rats were randomly divided into four equal groups as follows: group I served as control, group II orally inoculated with E. coli O157:H7 at a dose of 1.0 × 109cfu/ml, group III orally received 250mg/kg BW T. vulgaris oil daily for 7days and group IV orally inoculated with E. coli O157:H7 as the same dose of group II and orally received T. vulgaris oil as the same dose and duration of group III. Bacterial challenge in groups II and IV was once at the beginning of experiment and administration of oil began after 72h from bacterial inoculation. At the end of the study, blood was sampled and complete blood picture, liver and kidney function alongside immunoglobulins and cytokines concentrations were estimated and tissues of large intestine (colon), liver and kidneys were collected for histopathological examinations. The results revealed that there was an increase of red blood cells count, hematocrit value and hemoglobin concentration besides white blood cells and thrombocytes counts and substantial increment of serum markers of hepatorenal damage such as the activities of transaminases and concentrations of bilirubin (total, direct and indirect), total proteins, albumin, creatinine and urea in E. coli O157:H7-challenged group. Also, there was a considerable increase in serum immunoglobulins M and G, interleukin 6 and 8 and tumor necrosis factor alpha as well as decreased serum alkaline phosphatase activity. Moreover, T. vulgaris oil could partially improve the hematological, biochemical and histopathological alterations induced by E. coli O157:H7 without any significant alterations in all measured parameters when used alone. The study concluded that the T. vulgaris oil relatively diminished the alterations in hematological parameters, hepatic and renal function markers and immune-inflammatory variables alongside the histopathological changes in different organs induced by E. coli O157:H7. The ameliorative effects of T. vulgaris oil are mediated through its anti-inflammatory, antioxidant and immunomodulatory activities.

Effects of Dietary Indole-3-Acetate Sodium on Laying Performance, Egg Quality, Serum Hormone Levels and Biochemical Parameters of Danzhou Chickens.

Simple SummaryThe laying performance of hens plays a major role in the production of laying hens because it determines the economic benefits of farmers. Indole-3-acetate sodium is a derivative of indole-3-acetate (a major plant growth hormone). This study shows that indole-3-acetate sodium inclusion in diets improved the serum reproductive hormone levels and egg production performance of Danzhou chickens. We found that indole-3-acetate sodium could be considered as an effective feed additive to improve the laying performance of hens, but more comprehensive studies need to be performed in the future.This study was conducted to investigate the effects of indole-3-acetate sodium (IAA-Na) inclusion in diets on the egg production performance, egg quality, intestinal tissue morphology, serum hormone levels and biochemical parameters of Danzhou chickens to preliminarily explore the efficacy of IAA-Na as a feed additive. A total of 192 Danzhou chickens (50 weeks old) were randomly assigned to 2 groups of 96. The diets for the treatment group consisted of the basal diets, supplemented with IAA-Na (200 mg/kg). The formal feeding trial lasted for four weeks. The results showed that the feed supplemented with IAA-Na not only increased the laying rate (p < 0.05) and egg yolk ratio (0.05 < p < 0.1), but also significantly reduced the feed:egg ratio (p < 0.05). In addition, the dietary supplementation of IAA-Na significantly increased the serum estradiol levels (p < 0.05) and decreased serum alkaline phosphatase activity (p < 0.05). Compared with the control group, the addition of IAA-Na to the diet had no significant effect on the intestinal tissue morphology or serum antioxidant capacity of Danzhou chickens. This study preliminarily provides evidence that dietary IAA-Na can improve laying performance, indicating that IAA-Na is a potentially effective feed additive for laying hens, but further studies are required before arriving at definite conclusions.

SO078APABETALONE, A BROMODOMAIN AND EXTRA-TERMINAL (BET) PROTEIN INHIBITOR, REDUCES ALKALINE PHOSPHATASE IN CVD PATIENTS, IN MICE, AND IN CELL CULTURE SYSTEMS

Abstract Background and Aims Elevated serum alkaline phosphatase (ALP) independently predicts major adverse cardiac events (MACE) by contributing to vascular calcification and endothelial dysfunction arising in chronic kidney disease (CKD) and cardiovascular disease (CVD). Apabetalone is an orally active inhibitor of bromodomain and extraterminal (BET) proteins – epigenetic readers that modulate gene expression involved in vascular inflammation and calcification. Here we examined apabetalone’s effects on ALP post-hoc in recent clinical trials, then performed mechanistic studies into apabetalone’s impact on tissue non-specific ALP (TNALP) expression in mice and cell culture. Method Serum ALP was determined in CVD patients in phase 2 trials (3 month ASSERT and 6 month SUSTAIN &amp; ASSURE) and in the phase 3 BETonMACE CVD outcomes trial, including subpopulations with CKD (eGFR&amp;lt;60 mL/min/1.73m2). Apabetalone’s effect on expression of TNALP (gene symbol ALPL) was examined in mice, cultured primary human hepatocytes (PHH), HepaRG, HepG2, vascular smooth muscle cells (VSMCs), and vascular endothelial cells by real-time PCR. TNALP protein levels were assessed by immunoblots and flow cytometry. ALP enzyme activity was measured in enzymatic assays. Results In phase 2 trials, baseline serum ALP independently predicted MACE (hazard ratio [HR] 1.6, 95% CI 1.2-2.2, p=0.001). In the 3 month ASSERT trial, apabetalone dose dependently reduced serum ALP (p&amp;lt;0.001 vs placebo). Prominent reductions in ALP were apparent in patients on apabetalone (n=331) vs placebo (n=166) in combined analysis of the ASSURE &amp; SUSTAIN trials (median % change -11 vs -3.2; p&amp;lt;0.001). In the subset with CKD, patients on apabetalone (n=69) had greater reduction in serum ALP than placebo (n=22; p=0.008). Strikingly, ALP reductions in phase 2 correlated with reduction in MACE (HR 0.58, 95% CI 0.44-0.77, p&amp;lt;0.001). Consistent with phase 2, BETonMACE saw serum ALP reduced by 6.8 U/L with apabetalone (n=1082) vs placebo (n=1070; p&amp;lt;0.001) at 24 weeks. At the conclusion of BETonMACE, fewer MACE occurred in the CKD subgroup with apabetalone (n=124) vs placebo (n=164; HR 0.50 95% CI 0.26-0.96 p=0.032). Neither apabetalone nor statins that control low-density lipoprotein cholesterol inhibited recombinant TNALP enzyme activity, implying that decreased serum ALP activity in patients reflected reduction in TNALP production rather than inhibition of the enzyme. Liver-derived TNALP accounts for ≈50% of circulating ALP. In the liver of mice on high fat diet, apabetalone or JQ1 (BET inhibitors with different chemical scaffolds) reduced Alpl mRNA (p&amp;lt;0.001) with corresponding trends in TNALP activity. In PHH, HepaRG, &amp; HepG2 cells, apabetalone dose dependently suppressed ALPL expression by 60-80%. In HepG2 cells, apabetalone reduced TNALP protein (&amp;gt;55%, p&amp;lt;0.001), enzyme activity (&amp;gt; 40%; p&amp;lt;0.001), and % of TNALP positive cells (15-30%; p&amp;lt;0.001). MZ1, which promotes degradation of BET proteins, downregulated ALPL / TNALP similar to apabetalone. In VSMCs, apabetalone or JQ1 suppressed ALPL gene expression, TNALP protein levels, and enzyme activity, leading to decreases in extracellular calcium deposition. In addition, apabetalone downregulated ALPL expression in human aortic, umbilical vein, and brain microvascular endothelial cells by 50-70%. Conclusion Apabetalone lowers serum ALP in clinical trials, which is consistent with reduced hepatic production of TNALP - the most abundant ALP isoform. Further, apabetalone downregulates ALPL gene expression in vascular cell types while reducing calcification. Together, BET-dependent epigenetic modulation of ALP by apabetalone can affect several pathogenetic processes, and thereby improve cardiovascular outcomes. This study provides insights to the CVD event reductions observed in the CKD subpopulation in the BETonMACE Phase 3 trial.

The Protective Role of Green Tea against Ethanol-mediated Bone Alterations in Adult Male Rabbits: Biochemical, Histological and Morphometrical Study

Background: Chronic alcohol abuse is a widespread clinical disorder. It leads to bone alterations, mainly osteoporosis. Next to water, tea (green or black) is the most widely consumed beverage in the world. Bone mineral density is affected by several compounds contained in tea extracts.Aim of the Work: Our work aimed to investigate the effects of alcohol on adult male rabbit's compact bone and the possible protective effect of green tea extract. (GTE)Material and Methods: Twenty-four young adult male rabbits were used. They were divided into equal 4 groups: normal control, green tea, ethanol (EtOH) and EtOH – green tea. After 120 days of treatment, all animals were anaesthetized and sacrificed. Blood ethanol and serum ionized calcium (iCa), phosphorus (P) and alkaline phosphatase (ALP) levels were estimated. Serum creatinine, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were estimated to determine renal and hepatic integrity. Femurs of each rabbit were processed for histological and morphometrical study.Results: Chronic alcohol ingestion resulted in a non_significant decrease in serum iCa level and a significant decrease in serum ALP activity. EtOH -treated rabbits did not differ from the controls in mean serum levels of ALT, AST, creatinine or phosphorus. Bone sections from EtOH- treated rabbits revealed multiple areas of degeneration in the thin cartilaginous plate. The trabeculae were thinner, shorter and fewer than those from controls. There was a significant decrease in osteoblast surface and a significant increase in osteoclast surface. Green tea supplementation resulted in marked improving of biochemical, histological and all histomorphometric parameters under investigation.Conclusion: From the foregoing, dangerous effects of alcohol on the bone became clear. So it is better to restrict its consumption. Natural products as green tea are able to protect against bone deterioration.

Genetically Engineering a Sheep Model of Hypophosphatasia

Hypophosphatasia (HPP) is a rare inherited disorder that affects the development of bones and teeth. The disease is caused by mutations in the tissue‐nonspecific alkaline phosphatase (TNSALP) gene (ALPL) and accompanied by a highly variable clinical presentation. Although HPP patient studies have advanced our understanding of HPP, as well as documented disease severity, the rarity of the disease combined with a lack of sufficient animal models has significantly delayed mechanistic understanding and therapeutic development. Similar to other human disease models, current HPP models have been engineered virtually exclusively in rodents – specifically mice harboring null or loss‐of‐function mutations. Although useful for modeling some features of HPP, these murine models do not faithfully represent the broad spectrum of human HPP clinical bone, muscle and tooth (odonto‐HPP) phenotypes. However, in sheep both Haversian bone remodeling and tooth development are analogous to humans with sheep TNSALP amino acid sequence sharing 89% identity with human. Thus, our objective was to generate a sheep model of HPP and we posit that ALPL mutation‐specific replacements in the sheep genome using CRISPR/Cas9 will produce a model that accurately phenocopies the bone and tooth pathophysiology of HPP. To genetically engineer a sheep model of HPP, a total of 52 in vitro genetically manipulated embryos were generated targeting the Exon 10 c.1077G&gt;A mutation using CRISPR/Cas9. Three embryos were implanted per recipient ewe and implantations were performed in a total of 17 recipient ewes. Nine ewe pregnancies were confirmed by the measurement of Pregnancy‐Associated Protein on post‐implantation day 35 and further validated by ultrasound. From 9 live newborn lambs, four were heterozygous for our specific point mutation (4/6), one compound heterozygous (1/6) and one homozygous (1/6) for a total mutation efficiency rate of 66.6% (6/9). Similar to HPP patients with the same mutation, mutant sheep have variable clinical expression accompanied with decreased bone formation and mineralization in tails observed by DXA as well as significantly and appropriately decreased serum alkaline phosphatase activity. Additionally, an apparent “shell tooth” phenotype is observed in mutant lambs, further suggesting a mutant exon 10 genotype/phenotype that more completely recapitulates human skeletal and odonto‐HPP.Support or Funding Information1. William Townsend Porter Pre‐doctoral Fellowship2. TAMU/Texas Heart Institute Center for Cell and Organ Biotechnology Innovation Kitchen GrantThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effects of a high dose of microbial phytase and myo-inositol supplementation on growth performance, tibia mineralization, nutrient digestibility, litter moisture content, and foot problems in broiler chickens fed phosphorus-deficient diets

A total of 660 one-day-old Ross 308 broiler chicks were randomly distributed into eleven dietary treatments. Treatments included a maize-soybean meal-based diet with recommended calcium (Ca) and non-phytate phosphorus (nPP) (positive control; PC), an nPP-deficient diet (negative control; NC), NC diets supplemented with different levels of phytase (0, 500, 1,000, 2,000, 3,000, 4,000, 5,000, and 6,000 FTU/kg), a NC diet plus 0.15% myo-inositol, and a NC diet with reduced Ca level (Ca to nPP ratio same as PC). Feeding the NC diet had no effects on birds' body weight (BW), weight gain (WG), feed intake (FI), and feed conversion ratio (FCR), but decreased (P <0.05) tibia P contents, crude protein (CP) digestibility, and serum P, but increased (P <0.05) serum alkaline phosphatase (ALP) activity at 21 d of age. Phytase supplementation at ≥4,000 FTU/kg improved (P <0.05) BW, WG and digestibility of nutrients. Feeding the NC diet resulted in greater (P <0.05) litter moisture content (42 d) and poorer gait score (21 d), but 4,000 and 6,000 FTU/kg phytase returned (P <0.05) these parameters to that of the PC. Supplemental myo-inositol increased (P <0.05) serum total protein, P retention, and decreased (P <0.05) litter moisture at 42 d of age. Feeding the low Ca NC diet increased (P <0.05) serum total protein, ileum Ca, P, and CP digestibility and decreased serum ALP activity, litter moisture and gait score compared to the NC group. In conclusion, phytase in a dose-dependent manner, especially at ≥4,000 FTU/kg levels, was effective in overcoming the negative consequences of NC diets, primarily due to the ability to improve nutrient utilization. In addition, reducing the Ca level or supplementation of inositol of NC diet can correct some the negative effects of feeding a NC diet confirming the negative effect of a wide Ca: P ratio in a P-deficient diet and suggesting that inositol may play a role in the response to phytase addition.

Molecular and clinical analysis of ALPL in a cohort of patients with suspicion of Hypophosphatasia.

Hypophosphatasia (HPP) is a rare autosomal dominant or recessive metabolic disorder caused by mutations in the tissue nonspecific alkaline phosphatase gene (ALPL). To date, over 300 different mutations in ALPL have been identified. Disease severity is widely variable with severe forms usually manifesting during perinatal and/or infantile periods while mild forms are sometimes only diagnosed in adulthood or remain undiagnosed. Common clinical features of HPP are defects in bone and tooth mineralization along with the biochemical hallmark of decreased serum alkaline phosphatase activity. The incidence of severe HPP is approximately 1 in 300,000 in Europe and 1 in 100,000 in Canada. We present the clinical and molecular findings of 83 probands and 28 family members, referred for genetic analysis due to a clinical and biochemical suspicion of HPP. Patient referrals included those with isolated low alkaline phosphatase levels and without any additional clinical features, to those with a severe skeletal dysplasia. Thirty-six (43.3%) probands were found to have pathogenic ALPL mutations. Eleven previously unreported mutations were identified, thus adding to the ever increasing list of ALPL mutations. Seven of these eleven were inherited in an autosomal dominant manner while the remaining four were observed in the homozygous state. Thus, this study includes a large number of well-characterized patients with hypophosphatasemia which has permitted us to study the genotype:phenotype correlation. Accurate diagnosis of patients with a clinical suspicion of HPP is crucial as not only is the disease life-threatening but the patients may be offered bone targeted enzymatic replacement therapy. © 2017 Wiley Periodicals, Inc.

Benign prenatal hypophosphatasia: a treatable disease not to be missed

Prenatal bowing of the long bones is often associated with severe bone dysplasias. We report a child who presented marked bowing of the long bones at birth but showed a relatively benign postnatal course with spontaneous improvement of bowing. The fetal imaging showed normal skeletal mineralization and normal chest and abdominal circumferences despite the limb bowing and shortening. Decreased serum alkaline phosphatase activity and elevated urine phosphoethanolamine was biochemically evident, and compound heterozygous mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene were identified, which confirmed the diagnosis of a benign form of prenatal hypophosphatasia. Benign prenatal hypophosphatasia should be considered in the differential diagnosis of congenital bowing of the long bones.

Effects of feed-borne Fusarium mycotoxins on performance, serum chemistry, and intestinal histology of New Zealand White fryer rabbits1

The objective of the present study was to determine the effects of feeding diets containing grains naturally contaminated with Fusarium mycotoxins to fryer rabbits. The efficacy of a glucomannan mycotoxin adsorbent (GMA) was also examined. Thirty 5-wk-old male New Zealand White rabbits were fed a control diet, a contaminated diet, or a contaminated diet + 0.2% GMA for 21 d. Experimental diets contained deoxynivalenol (DON; vomitoxin) at a concentration of 0.25, 4.3, and 4.9 μg/g, respectively. Feed intake was measured daily and water intake was measured every 3 d. At the end of the feeding period, blood was collected for evaluation of serum chemistry and hematology. Visceral organs were excised, weighed, and processed for histopathological examination. Body weight gain and water intake were greater in rabbits fed the contaminated diet (P = 0.075 and 0.020, respectively) and those fed the contaminated + GMA diet (P = 0.026 and 0.002, respectively) compared with controls. Rabbits fed the contaminated + GMA diet had significantly increased serum urea concentrations (P = 0.023) and decreased serum alkaline phosphatase activity (P = 0.020) compared with controls. Increase in BW gain of rabbits fed the contaminated diets was caused by increased water consumption. There was no effect (P > 0.05) of diet on relative organ weights, but decreased infiltrations with eosinophilic granulocytes were observed in different regions of the intestine in rabbits fed the contaminated or the contaminated + GMA diet. It was concluded that rabbits could be adversely affected by feed-borne Fusarium mycotoxins but appear to be less sensitive than other mammalian species. Supplementation with GMA did not reduce many of the effects of feed-borne mycotoxins.

Adult hypophosphatasia with painful periarticular calcification treated with surgical resection

Hypophosphatasia is a rare inherited disorder characterized by a low serum alkaline phosphatase (ALP) activity and defective bone mineralization. Adult hypophosphatasia typically manifests in middle-age as a result of osteomalacia with recurrent stress fractures of the lower limb. However, considerable variation occurs in the clinical expression of hypophosphatasia, and no curative treatment has yet been established. We herein report a case of adult hypophosphatasia with painful calcific periarthritis, which showed improvement after surgical resection. A 32-year-old male was referred to our clinic complaining of pain in his elbows and knees. A painful subcutaneous mass was palpable on his right lateral epicondyle, where periarticular calcification was detected by plain radiography. The laboratory data showed a slight decrease in serum ALP activity and bone mineral density, and an elevation in the urinary phosphoethanolamine. Genomic DNA sequencing revealed an F310L mutation and a Y246H polymorphism in the tissue-nonspecific alkaline phosphatase gene, confirming the diagnosis of hypophosphatasia. The pain in the patient's right elbow was not responsive to nonsteroidal anti-inflammatory drugs, and triamcinolone diacetate was locally injected for treatment. His symptoms were ameliorated after the injection; however, they recurred in 3months, and he became refractory to additional steroid injection. Surgical debridement of the calcified lesion was performed, and his symptoms were successfully ameliorated after the surgery.

Effects of dietary cholesterol restriction in a feline model of Niemann-Pick type C disease.

A feline model of Niemann-Pick disease type C (NPC) was employed to evaluate the effect of dietary cholesterol restriction on progression of disease. Two NPC-affected treated cats were fed a cholesterol-restricted diet beginning at 8 weeks of age; the cats remained on the diet for 150 and 270 days respectively. The study goal was to lower the amount of low density lipoprotein (LDL) available to cells, hypothetically reducing subsequent lysosomal accumulation of unesterified cholesterol and other lipids. Neurological progression of disease was not altered and dietary cholesterol restriction did not significantly decrease storage in NPC-affected treated cats. One NPC-affected treated cat had decreased serum alkaline phosphatase activity (ALP) and decreased serum cholesterol concentration. Liver lipid concentrations of unesterified cholesterol, cholesterol ester and phospholipids in NPC-affected treated cats were similar to those seen in NPC-affected untreated cats. Ganglioside concentrations in the NPC-affected treated cats and NPC-affected untreated cats were similar. Histological findings in liver sections from NPC-affected treated cats showed a diffuse uniform microvacuolar pattern within hepatocytes and Kupffer cells, in contrast to a heterogeneous macro/microvacuolar pattern and prominent nodular fibrosis in NPC-affected untreated cats. Similar differences in vacuolar patterns were seen in splenic macrophages. Although some hepatic parameters were modified, dietary cholesterol restriction did not appear to alter disease progression in NPC-affected kittens.

Oral and parenteral vaccination of mice with protein-ergotamine conjugates and evaluation of protection against fescue toxicosis

Acremonium coenophialum produces ergopeptide alkaloids in tall fescue ( Festuca arundinacea Schreb.). These ergot alkaloids decrease serum alkaline phosphatase (ALP) activity, serum cholesterol and prolactin concentrations, as well as average daily gains (ADG) in cattle. The objective of this study was to evaluate the protection of anti-ergotamine antibodies induced by either oral or parenteral vaccination with protein-ergotamine conjugates or passive vaccination with anti-ergovaline, monoclonal antibodies in a murine model of fescue toxicosis. Ergotamine (EG) was conjugated to bovine serum albumin (BSA) and cholera toxin subunit B (CTB) by the Mannich reaction. Mice were blocked based on weight and randomly allocated into five groups of 10 mice each. Treatment groups were as follows: (1) group vaccinated intraperitoneally (ip) with a BSA–EG conjugate and fed an endophyte-infected (EI) fescue diet (BSA–EG group); (2) group orally vaccinated with a CTB–EG conjugate mixed with free cholera toxin (CT) and fed an EI fescue diet (CTB–EG group); (3) nonvaccinated group fed an EI fescue diet (EI group); (4) group passively vaccinated with anti-ergovaline, monoclonal antibodies and fed an EI fescue diet (MoAB group); and (5) nonvaccinated group fed an endophyte-free (EF) fescue diet (EF group). The EI diet contained 1.5 ppm of Ergovaline (EV), whereas no EV was detected in the EF diet. Respective diets were similar upon nutritional analysis. Unvaccinated mice in the EI group exhibited features of fescue toxicosis as indicated by decreased serum ALP activity and cholesterol, and decreased weight gain as compared to mice in the EF group. Antibodies against EG and EV were present in sera of mice in the BSA–EG and MoAB groups, respectively. Mice orally vaccinated with the CTB–EG conjugate developed secretory IgA (sIgA) antibodies and short-lived, systemic IgG responses against EG. Weight gains were increased in the BSA–EG and CTB–EG groups and tended to be increased in the MoAB group vs. the unvaccinated EI group. Serum ALP activity was decreased in the BSA–EG and MoAB groups as compared to the EF group. Serum ALP activity was further decreased in the BSA–EG vaccinated group as compared to the EI group. Cholesterol concentrations were decreased in the EI, BSA–EG and MoAB groups as compared to the EF group. Prolactin concentrations were similar in all groups.

Alkaline phosphatase: placental and tissue-nonspecific isoenzymes hydrolyze phosphoethanolamine, inorganic pyrophosphate, and pyridoxal 5'-phosphate. Substrate accumulation in carriers of hypophosphatasia corrects during pregnancy.

Hypophosphatasia features selective deficiency of activity of the tissue-nonspecific (liver/bone/kidney) alkaline phosphatase (ALP) isoenzyme (TNSALP); placental and intestinal ALP isoenzyme (PALP and IALP, respectively) activity is not reduced. Three phosphocompounds (phosphoethanolamine [PEA], inorganic pyrophosphate [PPi], and pyridoxal 5'-phosphate [PLP]) accumulate endogenously and appear, therefore, to be natural substrates for TNSALP. Carriers for hypophosphatasia may have decreased serum ALP activity and elevated substrate levels. To test whether human PALP and TNSALP are physiologically active toward the same substrates, we studied PEA, PPi, and PLP levels during and after pregnancy in three women who are carriers for hypophosphatasia. Hypophosphatasemia corrected during the third trimester because of PALP in maternal blood. Blood or urine concentrations of PEA, PPi, and PLP diminished substantially during that time. After childbirth, maternal circulating levels of PALP decreased, and PEA, PPi, and PLP levels abruptly increased. In serum, unremarkable concentrations of IALP and low levels of TNSALP did not change during the study period. We conclude that PALP, like TNSALP, is physiologically active toward PEA, PPi, and PLP in humans. We speculate from molecular/crystallographic information, indicating significant similarity of structure of the substrate-binding site of ALPs throughout nature, that all ALP isoenzymes recognize these same three phosphocompound substrates.

Significance of low serum alkaline phosphatase activity in a predominantly adult male population

The causes for low serum alkaline phosphatase (ALP) activity (reference range 30-115 U/L) in a large Veterans Medical Center were reviewed. Of 69,864 ALP determinations made over a 4-year period, 130 were low (< 30 U/L, 0.19%), representing 88 individual patients. Of these, 83 (primarily men, 96%) patients' charts were reviewed and classified into two groups, those with and those without conditions previously reported to be associated with decreased serum ALP activity: 47% had conditions associated with low ALP activity, the most frequent being cardiac surgery and cardiopulmonary bypass (26.5%), malnutrition (12.0%), magnesium deficiency (4.8%), hypothyroidism (2.4%), and severe anemia (1.2%); 53% of patients did not have clinical conditions previously associated with low ALP activity. No case of clinically apparent hypophosphatasia, for which low ALP activity is the defining characteristic, was found in this population of veterans. A low serum ALP may be of significance in other patient populations such as children, where it is associated with achondroplasia and cretinism, or in postmenopausal women with osteoporosis taking estrogen replacement therapy. In the predominantly adult male population in this study, low ALP activity was rare; it was seen most frequently in cardiac surgery patients postoperatively, a clinical condition heretofore not commonly associated with low serum ALP activity.

Calcitonin treatment of immobilization osteoporosis in rats

We studied changes in bone mass induced by immobilization and the ability of salmon calcitonin to inhibit immobilization osteoporosis in rat. The bone mass of the immobilized hind leg of rat was compared with the contralateral non-treated leg. Neurectomy and cast immobilization reduced the bone mineral mass to an equal extent. However, the dose-response of calcitonin was different with these immobilization techniques. Calcitonin 15 IU kg-1 administered once daily reduced bone ash weight difference significantly after 2 weeks' neurectomy (P less than 0.001). This had no significant effect on the bone loss induced by cast immobilization, but the dose had to be delivered as two injections given every 12 h. Two weeks' immobilization decreased the incorporation of 45Ca into bones. Calcitonin could not prevent this. However, calcitonin tended to inhibit the overall incorporation of 45Ca into bones in immobilized rats but yet had no effect on 45Ca incorporation in non-immobilized rats. Immobilization decreased serum alkaline phosphatase activity in cast-immobilized animals. Neurectomy did not change serum alkaline phosphatase activity from a sham operation level. The tartrate-resistant acid phosphatase to total acid phosphatase ratio in the serum increased significantly in neurectomized rats and in cast-immobilized calcitonin-treated rats.

Change in alkaline phosphatase activity in rats administered cadmium chloride.

When cadmium (CdCl2) was administered subcutaneously in a high single dose of 5.0 mg/kg to rats, their liver and testis tissues showed a statistically significant increase in alkaline phosphatase (Al-P) activity at 24 h or more after the administration while the reverse was the case in the serum of the rats. Lactate dehydrogenase (LDH) activity in the serum showed a statistically significant decrease at 15 to 24 h after the administration of CdCl2. An increase in LDH activity for the serum coincided with that for the testis. During the study period there was no change in the calcium level in the serum, but the level of zinc in the serum decreased in a similar fashion to serum Al-P activity. As for the level of cadmium in the serum, it showed a very high value (ca. 0.03 mM) at 15 and 24 h after CdCl2 administration. When this concentration of cadmium was added in the form of CdCl2 to rat serum in vitro, it produced an inhibitory effect on serum Al-P activity. These facts suggest that the decrease in serum Al-P activity is not due to a change in tissue levels of Al-P, but reflects a direct inhibition of Al-P activity in the serum by cadmium.

Decreased serum alkaline phosphatase activity in hypothyroidism: possible relationship to low serum zinc and magnesium.

Decreased serum alkaline phosphatase activity in hypothyroidism: possible relationship to low serum zinc and magnesium.

Enzyme Changes in Mallard Ducks Fed Iron or Lead Shot

Levels of serum glutamic pyruvic transaminase (SGPT), serum glutamic oxalacetic transaminase (SGOT), and serum alkaline phosphatase (SAP) were measured in duck blood. Enzyme activity of groups receiving up to 64 iron shot orally did not differ significantly (p <0.05) from that of controls. Significant increases in SGPT and decreases in SAP accompanied oral lead poisoning. Levels of GOT and GPT, but not AP, were much higher in control red cells than in plasma or serum. Among the tissues studied, heart contained the greatest relative amount of GOT and among the least relative amounts of GPT and AP. Kidney contained the highest relative concentrations of GPT, while duodenum and kidney had the highest AP levels. The increase in SGPT of lead-poisoned ducks may reflect hepatic, renal, or skeletal muscle damage, although this damage was not associated with a significant increase in SGOT. The decreased SAP activity probably reflected a direct inhibition of the enzyme by lead. 22 references, 3 figures, 1 table.