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1.
Osteoarthritis Cartilage ; 32(7): 943-951, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38648877

ABSTRACT

OBJECTIVE: To explore associations between hip muscle strength and cartilage defects (presence and severity) on magnetic resonance imaging (MRI) in young adults with hip/groin pain participating in sub-elite football. DESIGN: Sub-elite football players with hip/groin pain (>6 months) completed assessments of isometric hip strength and functional task performance. Hip cartilage defects were assessed using the Scoring Hip Osteoarthritis with MRI tool. This exploratory, cross-sectional study used logistic and negative binomial models to assess the relationships between hip muscle strength or functional task performance and hip cartilage defects, controlling for body mass index, age, testing site and cam morphology, incorporating sex-specific interaction terms. RESULTS: One hundred and eighty-two (37 women) sub-elite (soccer or Australian football) players with hip/groin pain (age 26 ± 7 years) were included. Greater hip extension strength was associated with higher cartilage total score (adjusted incidence rate ratio [aIRR] 1.01, 95%CI: 1.0 to 1.02, p = 0.013) and superolateral cartilage score (adjusted odds ratio (aOR) 1.03, 95% confidence interval (CI): 1.01 to 1.06, p < 0.01). In female sub-elite football players, greater hip external rotation strength was associated with lateral cartilage defects (aOR 1.61, 95%CI: 1.05 to 2.48, p = 0.03) and higher cartilage total score (aIRR 1.25, 95%CI: 1.01 to 1.66, p = 0.042). A one-repetition increase in one-leg rise performance was related to lower odds of superomedial cartilage defects (aOR 0.96, 95%CI: 0.94 to 0.99, p < 0.01). CONCLUSIONS: Overall, there were few associations between peak isometric hip muscle strength and overall hip cartilage defects. It is possible that other factors may have relevance in sub-elite football players. Additional studies are needed to support or refute our findings that higher one leg rise performance was associated with reduced superomedial cartilage defect severity and greater hip extension strength was related to higher cartilage defect severity scores.


Subject(s)
Cartilage, Articular , Hip Joint , Magnetic Resonance Imaging , Muscle Strength , Soccer , Humans , Male , Female , Muscle Strength/physiology , Adult , Cross-Sectional Studies , Cartilage, Articular/diagnostic imaging , Cartilage, Articular/physiopathology , Young Adult , Hip Joint/physiopathology , Hip Joint/diagnostic imaging , Groin/physiopathology , Arthralgia/physiopathology , Osteoarthritis, Hip/physiopathology , Osteoarthritis, Hip/diagnostic imaging , Adolescent
2.
Osteoarthritis Cartilage ; 31(2): 144-157, 2023 02.
Article in English | MEDLINE | ID: mdl-36402349

ABSTRACT

BACKGROUND: The general health benefits of running are well-established, yet concern exists regarding the development and progression of osteoarthritis. AIM: To systematically review the immediate (within 20 min) and delayed (20 min-48 h) effect of running on hip and knee cartilage, as assessed using magnetic resonance imaging (MRI). METHOD: Studies using MRI to measure change in hip or knee cartilage within 48 h pre- and post-running were identified. Risk of bias was assessed using a modified Newcastle-Ottawa Scale. Percentage change in cartilage outcomes were estimated using random-effects meta-analysis. Certainty of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation tool. RESULTS: Twenty-four studies were included, evaluating 446 knees only. One third of studies were low risk of bias. Knee cartilage thickness and volume decreased immediately after running, with declines ranging from 3.3% (95% confidence interval [CI]: 2.6%, 4.1%) for weight-bearing femoral cartilage volume to 4.9% (95% CI: 4.43.6%, 6.2%) for patellar cartilage volume. T1ρ and T2 relaxation times were also reduced immediately after running, with the largest decline being 13.1% (95% CI: -14.4%, -11.7%) in femoral trochlear cartilage. Tibiofemoral cartilage T2 relaxation times recovered to baseline levels within 91 min. Existing cartilage defects were unchanged within 48 h post-run. CONCLUSIONS: There is very low certainty evidence that running immediately decreases the thickness, volume, and relaxation times of patellofemoral and tibiofemoral cartilage. Hip cartilage changes are unknown, but knee changes are small and appear transient suggesting that a single bout of running is not detrimental to knee cartilage.


Subject(s)
Cartilage, Articular , Osteoarthritis, Knee , Patellofemoral Joint , Running , Humans , Patellofemoral Joint/diagnostic imaging , Patellofemoral Joint/pathology , Cartilage, Articular/diagnostic imaging , Cartilage, Articular/pathology , Knee Joint/diagnostic imaging , Knee Joint/pathology , Osteoarthritis, Knee/diagnostic imaging , Osteoarthritis, Knee/pathology , Magnetic Resonance Imaging/methods
3.
Andrology ; 6(4): 542-546, 2018 07.
Article in English | MEDLINE | ID: mdl-29752772

ABSTRACT

Preliminary evidence suggests that sex steroid hormones, such as danazol (a synthetic sex steroid hormone), may be involved in enhancing telomerase activity. Elucidating underlying mechanisms of telomerase activity may further therapeutic options for individuals with telomeropathies and potentially avert certain age-related conditions. Therefore, we conducted a cross-sectional study to investigate the relationship between circulating sex steroid hormones and SHBG with leukocyte telomere length among 499 males in NHANES (1999-2002 surveys). Sample-weighted linear regression analyses were conducted to assess age-adjusted and multivariable-adjusted estimates of associations. Estimates were rescaled to represent telomere length change in base pairs per half the value of the interquartile range of the independent variable. Estradiol and free estradiol were significantly inversely associated with leukocyte telomere length (ßcontinuous per §IQR  = -61, p = 0.04; free estradiol ßcontinuous per §IQR  = -67, p = 0.03). Testosterone, free testosterone, androstanediol glucuronide, and SHBG were not associated with leukocyte telomere length. The inverse association seen in this study indicates that a danazol-induced hypoestrogenic state could partly underlie the previously observed association between danazol therapy and increased leukocyte telomere length.


Subject(s)
Gonadal Steroid Hormones/blood , Telomere Homeostasis/physiology , Telomere/metabolism , Adult , Aged , Cross-Sectional Studies , Humans , Leukocytes/metabolism , Male , Middle Aged , Nutrition Surveys , Sex Hormone-Binding Globulin/metabolism
4.
Matern Child Health J ; 22(6): 786-793, 2018 06.
Article in English | MEDLINE | ID: mdl-29427015

ABSTRACT

INTRODUCTION: Recent research suggests that health disparities among low-SES and ethnic minority populations may originate from prenatal and early life exposures. Postpartum maternal depressive symptoms have been linked to poorer infant physical health, yet prenatal depressive symptoms not been thoroughly examined in relation to infant health. METHODS: In a prospective study of low-income Mexican American mothers and their infants, women (N = 322, median age 27.23, IQR = 22.01-32.54) completed surveys during pregnancy (median gestation 39.50, IQR = 38.71-40.14 weeks) and 12 weeks after birth. We investigated (1) if prenatal depressive symptoms predicted infant physical health concerns at 12 weeks of age, (2) whether these associations occurred above and beyond concurrent depressive symptoms, and (3) if birth weight, gestational age, and breastfeeding were mediators of prenatal depression predicting subsequent infant health. RESULTS: Higher prenatal depressive symptoms were associated with more infant physical health concerns at 12 weeks (p < .001), after accounting for 12-week maternal depressive symptoms, breastfeeding, gestational age, and birth weight. Twelve-week maternal depressive symptoms were concurrently associated with more infant health concerns (p < .01). Birth weight, gestational age, and breastfeeding were not associated with maternal depression or infant health concerns. DISCUSSION: Results establish a link between prenatal depressive symptoms and an elevated risk of poor health evident shortly after birth. These findings underscore the importance of the prenatal period as a possible sensitive period for infants' health, and the need for effective interventions for depression during pregnancy to mitigate potentially teratogenic effects on the developing fetus and reduce risks for later health concerns.


Subject(s)
Depression/psychology , Infant Health , Mexican Americans/psychology , Mothers/psychology , Pregnancy Complications/psychology , Adult , Depression/epidemiology , Female , Humans , Infant , Infant, Newborn , Mexican Americans/statistics & numerical data , Mother-Child Relations , Poverty , Pregnancy , Pregnancy Complications/epidemiology , Prenatal Care , Prospective Studies
5.
Patient Educ Couns ; 100(9): 1680-1687, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28433407

ABSTRACT

OBJECTIVE: To compare the relative quantity of talk between providers, caregivers, and adolescents and young adults (AYAs) with chronic kidney disease (CKD) and how communication differs by age. METHODS: During nephrology clinic visits, conversations between AYAs with CKD (N=99, ages 11-20, median=15), their caregivers, and providers (N=19) were audiotaped and coded using the Roter Interaction Analysis System. Linear mixed models tested AYA age differences in talk frequency by AYAs, caregivers, and providers. Post-hoc analyses tested differences in talk using AYA age groups. RESULTS: During clinic visits, providers spoke the most (63.7%), and caregivers spoke more (22.6%) than AYAs (13.7%). Overall talk differed by AYA age in AYAs (p<0.001) and caregivers (p<0.05), but not providers. Higher AYA age was associated with more AYA talk (biomedical information-giving, partnering, rapport-oriented) and less caregiver biomedical information-giving (ps<0.001-0.05). In post-hoc analyses, young adults talked more than adolescents; caregiver talk decreased in the middle-adolescent group. CONCLUSIONS: Increases in AYA talk occur primarily in young adulthood, whereas caregiver talk decreases in middle adolescence. This may indicate an appropriate developmental shift but raises concerns about conversational gaps during middle-adolescence. PRACTICE IMPLICATIONS: During transition-oriented treatment planning, providers should engage both AYAs and caregivers to avoid potential gaps in communication.


Subject(s)
Caregivers/psychology , Communication , Patient Participation/methods , Physician-Patient Relations , Renal Insufficiency, Chronic/therapy , Adolescent , Adult , Child , Humans , Male , Nephrology , Patient-Centered Care , Tape Recording , United States , Young Adult
6.
Int J Cancer ; 140(11): 2451-2460, 2017 06 01.
Article in English | MEDLINE | ID: mdl-28257597

ABSTRACT

Internationally, ovarian cancer is the 7th leading cancer diagnosis and 8th leading cause of cancer mortality among women. Ovarian cancer incidence varies by region, particularly when comparing high vs. low-income countries. Temporal changes in reproductive factors coupled with shifts in diagnostic criteria may have influenced incidence trends of ovarian cancer and relative rates by histologic subtype. Accordingly, we evaluated trends in ovarian cancer incidence overall (1973-1977 to 2003-2007) and by histologic subtype (1988-1992 to 2003-2007) using volumes IV-IX of the Cancer Incidence in Five Continents database (CI5plus) and CI5X (volume X) database. Annual percent changes were calculated for ovarian cancer incidence trends, and rates of histologic subtypes for individual countries were compared to overall international incidence. Ovarian cancer incidence rates were stable across regions, although there were notable increases in Eastern/Southern Europe (e.g., Poland: Annual Percent Change (APC) 1.6%, p = 0.02) and Asia (e.g., Japan: APC 1.7%, p = 0.01) and decreases in Northern Europe (e.g., Denmark: APC -0.7%, p = 0.01) and North America (e.g., US Whites: APC -0.9%, p < 0.01). Relative proportions of histologic subtypes were similar across countries, except for Asian nations, where clear cell and endometrioid carcinomas comprised a higher proportion of the rate and serous carcinomas comprised a lower proportion of the rate than the worldwide distribution. Geographic variation in temporal trends of ovarian cancer incidence and differences in the distribution of histologic subtype may be partially explained by reproductive and genetic factors. Thus, histology-specific ovarian cancer should continue to be monitored to further understand the etiology of this neoplasm.


Subject(s)
Ovarian Neoplasms/epidemiology , Ovarian Neoplasms/pathology , Databases, Factual , Female , Humans , Incidence , Registries
7.
J Appl Physiol (1985) ; 107(1): 54-62, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19074571

ABSTRACT

Spaceflight and bed rest models of microgravity have profound effects on physiological systems, including the cardiovascular, musculoskeletal, and immune systems. These effects can be exacerbated by suboptimal nutrient status, and therefore it is critical to monitor nutritional status when evaluating countermeasures to mitigate negative effects of spaceflight. As part of a larger study to investigate the usefulness of artificial gravity as a countermeasure for musculoskeletal and cardiovascular deficits during bed rest, we tested the hypothesis that artificial gravity would have an effect on some aspects of nutritional status. Dietary intake was recorded daily before, during, and after 21 days of bed rest with artificial gravity (n = 8) or bed rest alone (n = 7). We examined body composition, hematology, general blood chemistry, markers of oxidative damage, and blood levels of selected vitamins and minerals before, during, and after the bed rest period. Several indicators of vitamin status changed in response to diet changes: serum alpha- and gamma-tocopherol and urinary 4-pyridoxic acid decreased (P < 0.001) and plasma beta-carotene increased (P < 0.001) in both groups during bed rest compared with before bed rest. A decrease in hematocrit (P < 0.001) after bed rest was accompanied by a decrease in transferrin (P < 0.001), but transferrin receptors were not changed. These data provide evidence that artificial gravity itself does not negatively affect nutritional status during bed rest. Likewise, artificial gravity has no protective effect on nutritional status during bed rest.


Subject(s)
Bed Rest/adverse effects , Gravity, Altered , Nutritional Status/physiology , Weightlessness Countermeasures , Adult , Antioxidants/analysis , Blood Chemical Analysis , Eating , Energy Intake/physiology , Hematologic Tests , Humans , Male , Trace Elements/blood , Vitamins/blood , Weightlessness/adverse effects , Weightlessness Simulation
8.
J Hum Nutr Diet ; 21(2): 117-28, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18339052

ABSTRACT

BACKGROUND: Recent research suggests that cardiovascular disease (CVD) and bone loss are functionally interwoven. This study examined the concomitant effects of a nutritional treatment of osteopaenia on CVD-risk factors. METHODS: A 1-year placebo-controlled trial was conducted on middle-aged women with normal (group A) or low (groups B and C) bone mineral density. Subjects (n = 20 per group) took daily either a placebo, calcium carbonate alone or combined to a vitamin (C and B(6))-proline capsule, respectively. Urinary pyridoxic acid (used to assess treatment compliance), plasma homocysteine, serum lipids and lipoproteins were measured before and after nutritional intervention. RESULTS: Groups were comparable at baseline in most parameters of interest. No changes occurred in groups A and B. The 4%, 7% and 25% reductions of total cholesterol, LDL and triglycerides, and 14% elevation of HDL were all significant in group C. A trend toward reduction was observed for homocysteine in this group. CONCLUSIONS: Vitamins C (500 mg) and B(6) (75 mg) combined with proline had consistent beneficial effects on CVD-risk factors, whereas calcium alone did not. This study also underlined the importance of considering vitamin B(6) status as a potential CVD risk factor.


Subject(s)
Bone Density Conservation Agents/therapeutic use , Bone Density/drug effects , Bone Diseases, Metabolic/drug therapy , Calcium, Dietary/therapeutic use , Cardiovascular Diseases/epidemiology , Adult , Ascorbic Acid/administration & dosage , Bone Diseases, Metabolic/blood , Calcium Carbonate/administration & dosage , Cardiovascular Diseases/blood , Cardiovascular Diseases/prevention & control , Cholesterol/blood , Drug Therapy, Combination , Female , Homocysteine/blood , Humans , Middle Aged , Patient Compliance , Postmenopause , Proline/administration & dosage , Pyridoxic Acid/urine , Risk Factors , Vitamin B 6/administration & dosage
9.
J Dent Res ; 84(11): 1021-5, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16246934

ABSTRACT

Hypophosphatasia (HPP) often leads to premature loss of deciduous teeth, due to disturbed cementum formation. We addressed the question to what extent cementum and dentin are similarly affected. To this end, we compared teeth from children with HPP with those from matched controls and analyzed them microscopically and chemically. It was observed that both acellular and cellular cementum formation was affected. For dentin, however, no differences in mineral content were recorded. To explain the dissimilar effects on cementum and dentin in HPP, we assessed pyrophosphate (an inhibitor of mineralization) and the expression/activity of enzymes related to pyrophosphate metabolism in both the periodontal ligament and the pulp of normal teeth. Expression of nucleotide pyrophosphatase phosphodiesterase 1 (NPP1) in pulp proved to be significantly lower than in the periodontal ligament. Also, the activity of NPP1 was less in pulp, as was the concentration of pyrophosphate. Our findings suggest that mineralization of dentin is less likely to be under the influence of the inhibitory action of pyrophosphate than mineralization of cementum.


Subject(s)
Dental Cementum/pathology , Dentin/pathology , Hypophosphatasia/pathology , Adolescent , Adult , Case-Control Studies , Cementogenesis/physiology , Child , Child, Preschool , Dental Cementum/chemistry , Dental Pulp/enzymology , Dentin/chemistry , Dentinogenesis/physiology , Diphosphates/analysis , Humans , Hypophosphatasia/metabolism , Hypophosphatasia/physiopathology , Infant , Microradiography , Minerals/analysis , Periodontal Ligament/enzymology , Phosphoric Diester Hydrolases/analysis , Pyrophosphatases/analysis , Tooth Calcification/physiology
10.
J Nutr Health Aging ; 9(1): 59-64, 2005.
Article in English | MEDLINE | ID: mdl-15750667

ABSTRACT

UNLABELLED: The risk of cardio vascular disease (CVD) doubles after menopause. Plasma homocysteine (hCy) is a risk factor which is influenced by vitamins B12,B6 and folate. The present study was conducted to examine the relationship of plasma hCy to the three vitamins and other contributing variables in early natural menopause. METHODS: Participants were healthy, non smoking Caucasian women 3 to 5 years postmenopausal (n = 26) or premenopausal between 30 and 45 y(n = 30). Anthropometric data, dietary records and plasma concentrations of hCy, vitamin B6, vitamin B12 and folate were obtained. RESULTS: The nutritional status of vitamins B6, B12 and folate as measured by dietary intake and blood concentrations was adequate in both groups. Mean fasting plasma total (t) hCy concentration of postmenopausal group was 2-fold higher than the value found for control group (P < 0.0001) without oral methionine loading. The difference between the two groups remained highly significant after adjustment for confounding variables by multivariate analysis, suggesting that the effect of estrogen deficiency was direct. CONCLUSION: In addition to the loss of the protective effects of estrogen on their cardiovascular physiology and lipid metabolism, postmenopausal women are exposed to higher plasma hCy concentrations and deleterious cardiovascular effects. The exact mechanism is not known but does not seem to be related to coenzyme deficiency.


Subject(s)
Cardiovascular Diseases/blood , Cardiovascular Diseases/epidemiology , Diet , Homocysteine/blood , Menopause/blood , Adult , Cardiovascular Diseases/enzymology , Coenzymes/blood , Coenzymes/metabolism , Estrogens/blood , Estrogens/deficiency , Estrogens/metabolism , Female , Folic Acid/blood , Folic Acid/metabolism , Humans , Middle Aged , Risk Factors , Vitamin B 12/blood , Vitamin B 12/metabolism , Vitamin B 6/blood , Vitamin B 6/metabolism
11.
Anal Biochem ; 298(2): 241-5, 2001 Nov 15.
Article in English | MEDLINE | ID: mdl-11700978

ABSTRACT

Since measurement of lysophosphatidate phosphatase activity is important in studies of tumorigenesis, we attempted to develop a simpler alternative to the more complex methods currently available. Measuring the phosphate released would permit use of the same method for a variety of phosphatases with physiological substrates, many of which are nonchromogenic. The Malachite green method of K. Itaya and M. Ui (1966, Clin. Chim. Acta 14, 361) has adequate sensitivity for quantitating phosphatase activity in biological samples. In samples with high endogenous phosphate concentrations pretreatment with 50 mg Dowex 1 x 10 (100-200 mesh, OH- form) usually permitted reliable determination of phosphatase activity. For 34 consecutive runs the mean relative difference [(phosphorus activity--vitamer activity)/phosphorus activity] obtained from the simultaneous measurement of both the phosphate released and the corresponding organic product (pyridoxal and pyridoxine) was -0.03 +/- 0.09. The within run and between run coefficients of variation (three runs of four to five replicates) were 0.05 and 0.04, respectively. Pyridoxine 5'-phosphate hydrolase activity (pH 10) in cultured skin cells (normal and cancerous) ranged from 2 to 12 nmol phosphorus/min. mg protein. Lysophosphatidate phosphatase activity (pH 7.4) ranged from 3 to 14 nmol phosphorus/min. mg protein. The current approach permits the measurement of phosphatase activity with a single method using a variety of substrates and incubation conditions.


Subject(s)
Alkaline Phosphatase/analysis , Lysophospholipids/chemistry , Phosphates/analysis , Skin/enzymology , Animals , Biological Assay , Carcinoma, Squamous Cell/enzymology , Cricetinae , Female , Humans , Hydrogen-Ion Concentration , Keratinocytes/enzymology , Male , Melanoma/enzymology , Mesocricetus , Mice , Mice, Inbred C57BL , Phosphorylation , Skin Neoplasms/enzymology , Substrate Specificity
12.
Phys Rev E Stat Nonlin Soft Matter Phys ; 63(3 Pt 1): 032602, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11308691

ABSTRACT

We report a high-resolution synchrotron grazing incidence x-ray diffraction measurement of a surface crystalline monolayer at the liquid-vapor interface of the n-alkane eicosane (C20H42) just above its melting temperature. The peak width of the surface monolayer rotator phase is shown to be resolution limited and implies positional correlations of at least approximately 1 microm. The high resolution allowed determination of the temperature dependence of the peak position over the narrow (3 degrees C) temperature range of the surface crystal phase. The two-dimensional thermal expansion was determined to be (dA/dT)/A=1.8(+/-0.1)x10(-3) degrees C-1, which is comparable to the expansion in similar chain length bulk n-alkane rotator phases. Our data are consistent with the power-law shaped scattering tails expected from quasi-long-range order in two dimensions.

13.
J Nutr ; 131(4): 1319-21, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11285344

ABSTRACT

In the last twenty years, powerful new molecular techniques were introduced that made it possible to advance knowledge in human biology using a reductionist approach. Now, the need for scientists to deal with complexity should drive a movement toward an integrationist approach to science. We propose that nutritional science is one of the best reservoirs for this approach. The American Society for Nutritional Sciences can play an important role by developing and delivering a cogent message that convinces the scientific establishment that nutrition fills this valuable niche. The society must develop a comprehensive strategy to develop our image as the reservoir for life sciences integration. Our efforts can start with our national meeting and publications, with the research initiatives for which we advocate, with our graduate training programs and with the public relations image we project for ourselves. Defining the image and future directions of nutrition as the discipline that can integrate scientific knowledge from the cell and molecule to the whole body and beyond to populations can be the most important task that our society undertakes. If we do not effectively meet this challenge, a golden opportunity will pass to others and nutritional scientists will be left to follow them.


Subject(s)
Nutritional Physiological Phenomena , Biological Science Disciplines/trends , Congresses as Topic , Education , Periodicals as Topic , Research Support as Topic , Societies , United States
14.
Am J Med Genet ; 86(5): 410-5, 1999 Oct 29.
Article in English | MEDLINE | ID: mdl-10508980

ABSTRACT

We describe four pregnancies in two families in which mild hypophosphatasia, apparently transmitted as an autosomal dominant trait, manifested in utero as severe long bone bowing. Postnatally, there was spontaneous improvement of the skeletal defects. Recognition of this presentation for hypophosphatasia by family investigation and assessment of the fetal skeleton for degree of ossification and chest size using ultrasonography is important. The prognosis for this condition is considerably better than for more severe forms of hypophosphatasia and for many other disorders that cause skeletal defects with long bone bowing in utero.


Subject(s)
Hypophosphatasia/embryology , Hypophosphatasia/genetics , Adult , Child, Preschool , Female , Genes, Dominant , Humans , Hypophosphatasia/physiopathology , Infant , Male , Ossification, Heterotopic/diagnostic imaging , Ossification, Heterotopic/embryology , Ossification, Heterotopic/genetics , Pedigree , Pregnancy , Ultrasonography, Prenatal
15.
J Nutr ; 129(10): 1905-8, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10498766

ABSTRACT

Shipping stress is an economic problem because of its effect on meat quality. Because shipping increases plasma cortisol and pyridoxal 5'-phosphate interacts with steroid hormones, we examined the interaction between adrenocorticotropic hormone (ACTH) and vitamin B-6 metabolism in pigs. Six crossbred pigs with ear vein catheters received 50 IU of porcine ACTH intravenously at 3-h intervals from 0800 to 2100 h on d 1-3 and 100 IU intramuscularly at 0800, 1400 and 2000 h on d 6 and 7. Controls received saline. ACTH had no effect on pyridoxal 5'-phosphate in adrenal tissue but decreased pyridoxamine 5'-phosphate from 6.1 +/- 0.7 to 4.7 +/- 1.0 nmol/g (P < 0.05). Adrenal pyridoxal and pyridoxamine concentrations were 0.4 +/- 0.1 nmol/g in controls and 1.1 +/- 0.3 and 1.3 +/- 0.5 nmol/g, respectively, in ACTH-treated pigs (P < 0.01). Pyridoxal 5'-phosphate phosphatase activity [median (25-75 percentile value)] at pH 7.4 in adrenal tissue was 66.6 (47.8-75.5) nmol/(g. min) in the controls and 764 (626-771) in the ACTH-treated pigs (P < 0.01). There was no significant difference in pyridoxal kinase activity. However, kinase activity in the adrenals was about twice as high as in other tissues. These data suggest an active turnover of vitamin B-6 in adrenal tissue.


Subject(s)
Adrenal Glands/drug effects , Adrenocorticotropic Hormone/pharmacology , Hydrocortisone/blood , Stress, Physiological/metabolism , Vitamin B Complex/metabolism , Adrenal Glands/metabolism , Adrenocorticotropic Hormone/administration & dosage , Alkaline Phosphatase/metabolism , Analysis of Variance , Animals , Hydrolysis/drug effects , Injections, Intramuscular , Injections, Intravenous , Male , Pyridoxal Kinase/metabolism , Salivary Glands/drug effects , Salivary Glands/metabolism , Swine
16.
J Bone Miner Res ; 14(12): 2015-26, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10620060

ABSTRACT

Hypophosphatasia is an inborn error of metabolism characterized by deficient activity of the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP) and skeletal disease due to impaired mineralization of cartilage and bone matrix. We investigated two independently generated TNSALP gene knock-out mouse strains as potential models for hypophosphatasia. Homozygous mice (-/-) had < 1% of wild-type plasma TNSALP activity; heterozygotes had the predicted mean of approximately 50%. Phosphoethanolamine, inorganic pyrophosphate, and pyridoxal 5'-phosphate are putative natural substrates for TNSALP and all were increased endogenously in the knock-out mice. Skeletal disease first appeared radiographically at approximately 10 days of age and featured worsening rachitic changes, osteopenia, and fracture. Histologic studies revealed developmental arrest of chondrocyte differentiation in epiphyses and in growth plates with diminished or absent hypertrophic zones. Progressive osteoidosis from defective skeletal matrix mineralization was noted but not associated with features of secondary hyperparathyroidism. Plasma and urine calcium and phosphate levels were unremarkable. Our findings demonstrate that TNSALP knock-out mice are a good model for the infantile form of hypophosphatasia and provide compelling evidence for an important role for TNSALP in postnatal development and mineralization of the murine skeleton.


Subject(s)
Alkaline Phosphatase/genetics , Hypophosphatasia/genetics , Age Factors , Alkaline Phosphatase/blood , Animals , Animals, Newborn , Body Weight/genetics , Disease Models, Animal , Heterozygote , Hindlimb/diagnostic imaging , Hindlimb/growth & development , Histocytochemistry , Homozygote , Hypophosphatasia/diagnostic imaging , Hypophosphatasia/metabolism , Mice , Mice, Knockout , Phosphates/urine , Phosphatidylethanolamines/urine , Pyridoxal Phosphate/blood , Radiography , Tibia/diagnostic imaging , Tibia/growth & development
17.
J Clin Endocrinol Metab ; 83(11): 3951-7, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9814474

ABSTRACT

Natural and artificial manipulation of tissue nonspecific alkaline phosphatase activity indicates that pyrophosphate, phosphoethanolamine, and pyridoxal 5'-phosphate are among the natural substrates for this enzyme. Although inorganic phosphate has been recognized as a competitive inhibitor of this enzyme for many years, the influence of phosphate on alkaline phosphatase activity in serum under physiological conditions has not been previously reported. We examined the kinetics of tissue nonspecific alkaline phosphatase from bovine kidney and sera from 49 patients with a wide range of endogenous phosphate concentrations using pyridoxine 5'-phosphate as a substrate at pH 7.4. For the bovine kidney enzyme, the Km was 0.42 +/- 0.04 micromol/L, and the Ki for phosphate was 2.4 +/- 0.2 micromol/L. Analysis of the kinetics using pyridoxine 5'-phosphate in undiluted serum from 10 subjects with phosphorus ranging from 0.5-2.1 mmol/L and alkaline phosphatase activity ranging from 41-165 nmol/min x mL gave estimates for the Km of 56 +/- 11 micromol/L and for the Ki of 540 +/- 82 micromol/L for phosphate. This indicates that under physiological conditions alkaline phosphatase activity toward pyridoxine 5'-phosphate is reduced approximately 50% by the normal phosphate concentration and that it will increase or decrease significantly in response to changes in phosphate concentration within the ranges observed clinically.


Subject(s)
Alkaline Phosphatase/blood , Enzyme Inhibitors/blood , Phosphates/blood , Adult , Aged , Alkaline Phosphatase/antagonists & inhibitors , Animals , Cattle , Female , Humans , Intestines/enzymology , Kidney/enzymology , Male , Middle Aged , Organ Specificity , Placenta/enzymology , Substrate Specificity
20.
Biochem J ; 317 ( Pt 2): 613-9, 1996 Jul 15.
Article in English | MEDLINE | ID: mdl-8713093

ABSTRACT

The majority of vitamin B6 in the body is in skeletal muscle, bound as the cofactor pyridoxal 5'-phosphate to one abundant protein, glycogen phosphorylase. Previous work has established that radiolabelled vitamin B6 can be used as a turnover label for glycogen phosphorylase. In this study, a stable isotope derivative of pyridoxine {dideuterated pyridoxine; 3-hydroxy-4-(hydroxymethyl) -5-[hydroxymethyl-2H2]-2-methylpyridine} ([2H2]PN) has been used as a metabolic tracer to study the kinetics of labelling of the body pools of vitamin B6 in mice. A non-invasive method was developed in which the isotope abundance of the urinary excretory product of vitamin B6 metabolism, 4-pyridoxic acid, was analysed by GC/MS. The change in isotope abundance of urinary 4-pyridoxic acid following administration of [2H2]PN reflects the kinetics of labelling of the body pools of vitamin B6, and yields, non-invasively, the rate of degradation of glycogen phosphorylase.


Subject(s)
Muscle, Skeletal/metabolism , Phosphorylases/metabolism , Pyridoxic Acid/urine , Pyridoxine/metabolism , Animals , Body Fluid Compartments , Deuterium , Gas Chromatography-Mass Spectrometry , Kinetics , Mice , Mice, Inbred BALB C , Models, Biological , Muscle, Skeletal/enzymology , Physiology/methods , Pyridoxine/analogs & derivatives
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