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1.
Phytochemistry ; 188: 112800, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34087511

ABSTRACT

The endemic Australian plants Lepidosperma sp. Flinders Chase (Cyperaceae), Lepidosperma viscidum (Cyperaceae) and Dodonaea humilis (Sapindaceae) were found to be the botanical origin of three propolis types found on Kangaroo Island identified by TLC and 1H NMR matching of propolis and plant resin analytical profiles. Resin samples extracted from the plant, Lepidosperma sp. Flinders Chase, were chromatographically fractionated to give: methyl 3-phenyl-2-(E-cinnamoyloxy)propanoate (1), 3-(E-8-methoxy-8-oxo-3,7-dimethyloct-2-enyl)-4-hydroxy-E-cinnamic acid (2), 3-(E-6,7-dihydroxy-3,7-dimethyloct-2-enyl)-4-hydroxy-E-cinnamic acid (3), previously undescribed; and the known stilbenes, 2-prenyl-3,5-dihydroxy-E-stilbene (6) and 2-prenyl-3-methoxy-5-hydroxy-E-stilbene (7). The resin from L. viscidum gave: 5'-(E-4-hydroxy-3-methylbut-2-enyl)-4,2',4'-trihydroxydihydrochalcone (4); 5'-(E-4-hydroxy-3-methylbut-2-enyl)-4'-methoxy-4,2'-dihydroxydihydrochalcone (5), previously undescribed; and three known flavanones, farrerol (8), 5,7,3',5'-tetrahydroxy-6,8-dimethylflavanone (9) and 5,7,3',5'-tetrahydroxy-6-methylflavanone (10). The major constituent in the propolis identified as being sourced from D. humilis was identified as 6,8-diprenyl-5,7,3',4'-tetrahydroxyflavanone (11), a known compound identified in several unrelated plant species.


Subject(s)
Cyperaceae , Propolis , Sapindaceae , Stilbenes , Australia
2.
Int J Sport Nutr Exerc Metab ; 28(1): 82-89, 2018 Jan 01.
Article in English | MEDLINE | ID: mdl-29035602

ABSTRACT

Amylomaize-7 is classified as a resistant corn starch and is 68% digestible. When modified by partial hydrolysis in ethanol and hydrochloric acid its digestibility is 92%, yet retains its low glycemic and insulinemic properties. The purpose of this study was to characterize the metabolic response when modified amylomaize-7 or dextrose is consumed in the hour before exercise, and to compare the effect on performance of a brief high-intensity cycling trial. Ten male, trained cyclists were given 1 g/kg body mass of dextrose (DEX) or modified amylomaize-7 (AMY-7) or a flavored water placebo (PL) 45 min prior to exercise on a cycle ergometer. A 15-min ride at 60% Wmax was immediately followed by a self-paced time trial (TT) equivalent to 15 min at 80% Wmax. When cyclists consumed DEX, mean serum glucose concentration increased by 3.3 ± 2.1 mmol/L before exercise, compared to stable serum glucose observed for AMY-7 or PL. Glucose concentrations returned to baseline by pre-TT in all treatments. However, the mean post-TT glucose concentration of the DEX group was significantly lower than baseline, AMY-7, or PL. Serum insulin concentration increased nine-fold from baseline to preexercise in the DEX trial, whereas PL or AMY-7 remained unchanged. Time required to complete the performance trial was not significantly different between DEX, AMY-7 or PL. Preexercise ingestion of modified amylomaize-7 compared to dextrose resulted in a more stable serum glucose concentration, but did not offer a performance advantage in this high-intensity cycling trial.


Subject(s)
Athletic Performance/physiology , Bicycling/physiology , Blood Glucose/analysis , Sports Nutritional Physiological Phenomena , Starch/administration & dosage , Exercise Test , Glucose/administration & dosage , Humans , Male , Young Adult
3.
Violence Vict ; 32(6): 1014-1023, 2017 12 01.
Article in English | MEDLINE | ID: mdl-29017642

ABSTRACT

Recent mass killings, such as those in Newtown, Connecticut, and Aurora, Colorado, have brought new attention to mass killings in the United States. This article examines 323 mass killings taking place between January 1, 2006, and October 4, 2016, to assess how they are distributed over time. In particular, we find that they appear to be uniformly distributed over time, which suggests that their rate has remained stable over the past decade. Moreover, analysis of subsets of these mass killings sharing a common trait (e.g., family killings, public killings) suggests that they exhibit a memoryless property, suggesting that mass killing events within each category are random in the sense that the occurrence of a mass killing event does not signal whether another mass killing event is imminent. However, the same memoryless property is not found when combining all mass killings into a single analysis, consistent with earlier research that found evidence of a contagion effect among mass killing events. Because of the temporal randomness of public mass killings and the wide geographic area over which they can occur, these results imply that these events may be best addressed by systemic infrastructure-based interventions that deter such events, incorporate resiliency into the response system, or impede such events until law enforcement can respond when they do occur.


Subject(s)
Homicide/statistics & numerical data , Mass Casualty Incidents , Homicide/legislation & jurisprudence , Homicide/psychology , Humans , Sex Factors , Spatio-Temporal Analysis , United States/epidemiology
4.
Curr Obes Rep ; 6(1): 3-9, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28243840

ABSTRACT

PURPOSE OF REVIEW: Traveling by automobile rather than walking or cycling can encourage obesity by eliminating physical activity. As national obesity rates in the USA have reached 37.9% in 2014, understanding the connections between obesity and transportation choices can help policymakers in the public health community propose effective obesity interventions at the national level. RECENT FINDINGS: Following from foundational studies examining associations between the built environment and leisure walking, recent studies consider a diverse set of transportation choices regarding mode (e.g., automobile, walking, public transit) and purpose (e.g., commuting, leisure), along with studies on the effectiveness of several transportation-related interventions for obesity. The reviewed studies point toward potential interventions for obesity; there is emerging evidence that commuting by public transit may be one such intervention. Moreover, new data-gathering tools such as global positioning systems, geographic information systems, and accelerometers may alleviate statistical obstacles in conducting future studies.


Subject(s)
Automobile Driving/psychology , Obesity/etiology , Transportation , Adult , Bicycling/physiology , Bicycling/psychology , Environment Design , Exercise/physiology , Exercise/psychology , Gasoline/statistics & numerical data , Humans , Leisure Activities/psychology , Walking/physiology , Walking/psychology , Workplace/psychology
5.
Prev Med ; 99: 264-268, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28322880

ABSTRACT

The objective of this paper is to estimate the impact of county-level public transit usage on obesity prevalence in the United States and assess the potential for public transit usage as an intervention for obesity. This study adopts an instrumental regression approach to implicitly control for potential selection bias due to possible differences in commuting preferences among obese and non-obese populations. United States health data from the 2009 Behavioral Risk Factor Surveillance System and transportation data from the 2009 National Household Travel Survey are aggregated and matched at the county level. County-level public transit accessibility and vehicle ownership rates are chosen as instrumental variables to implicitly control for unobservable commuting preferences. The results of this instrumental regression analysis suggest that a one percent increase in county population usage of public transit is associated with a 0.221 percent decrease in county population obesity prevalence at the α=0.01 statistical significance level, when commuting preferences, amount of non-travel physical activity, education level, health resource, and distribution of income are fixed. Hence, this study provides empirical support for the effectiveness of encouraging public transit usage as an intervention strategy for obesity.


Subject(s)
Obesity/epidemiology , Transportation/statistics & numerical data , Travel/statistics & numerical data , Behavioral Risk Factor Surveillance System , Environment Design , Humans , United States/epidemiology
6.
Phytochemistry ; 134: 87-97, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27890584

ABSTRACT

Propolis samples from Kangaroo Island, South Australia, were investigated for chemical constituents using high-field nuclear magnetic resonance spectral profiling. A type of propolis was found containing a high proportion of prenylated hydroxystilbenes. Subsequently, the botanical origin of this type of propolis was identified using a beehive propolis depletion method and analysis of flora. Ligurian honey bees, Apis mellifera ligustica Spinola, were found to produce propolis from resin exuded by the Australian native sedge plant Lepidosperma sp. Montebello (Cyperaceae). The plants, commonly known as sword sedge, were found to have resin that matched with the propolis samples identified as the most abundant propolis type on the island containing C- and O-prenylated tetrahydroxystilbenes (pTHOS) in addition to a small amount of prenylated p-coumarate. The isolation of five pTHOS not previously characterized are reported: (E)-4-(3-methyl-2-buten-1-yl)-3,4',5-trihydroxy-3'-methoxystilbene, (E)-2,4-bis(3-methyl-2-buten-1-yl)-3,3',4',5-tetrahydroxystilbene, (E)-2-(3-methyl-2-buten-1-yl)-3-(3-methyl-2-butenyloxy)-3',4',5-trihydroxystilbene, (E)-2,6-bis(3-methyl-2-buten-1-yl)-3,3',5,5'-tetrahydroxystilbene and (E)-2,6-bis(3-methyl-2-buten-1-yl)-3,4',5-trihydroxy-3'-methoxystilbene. A National Cancer Institute 60 human cell line anticancer screen of three of these compounds showed growth inhibitory activity. The large Australasian genus Lepidosperma is identified as a valuable resource for the isolation of substances with medicinal potential.


Subject(s)
Antineoplastic Agents/isolation & purification , Cyperaceae/chemistry , Propolis/chemistry , Stilbenes/isolation & purification , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Australia , Bees , Coumarins/chemistry , Coumarins/isolation & purification , Macropodidae , Prenylation , Stilbenes/chemistry
7.
J Leukoc Biol ; 97(5): 873-885, 2015 May.
Article in English | MEDLINE | ID: mdl-25765676

ABSTRACT

Adaptive immune responses are initiated by resident myeloid tissue DC. A major fraction of tissue DC express CD1c+ and is thought to be derived from blood CD1c DC, an idea supported here by the observation that they express tissue-homing molecules and rapidly differentiate into cells with a tissue DC phenotype. Responses are thought to be augmented/modulated further by inflammatory moDC. Although much accepted human myeloid DC cell biology is based on moDC studies, we find these 2 DC populations to be functionally distinct. Stimulated moDC produce high levels of IL-10 and the Th1-promoting cytokine IL-12. Under identical conditions, CD1c DC synthesized no IL-10 and no or low levels of IL-12. Despite this, CD1c DC stimulated a strong Th1 response, demonstrated by IL-12 neutralization to be IL-12 independent, whereas the response induced by moDC was IL-12 dependent. This finding was supported by studies on a patient with a highly reduced ability to synthesize IL-12, whose CD1c DC induced a good Th1 response contrasting with the failure of his moDC, which were impaired in IL-12 production, to induce IFN-γ-secreting T cells. The IL-10 and IL-12 data were confirmed by microarray analysis, which also showed that stimulated moDC produced inflammatory-associated chemokines and cytokines, whereas stimulated CD1c DC showed minimal up-regulation of these genes. Thus, moDC, widely used as a human myeloid DC model, do not faithfully reflect the properties of CD1c tissue DC, making the initial response to a pathogen or vaccine.

8.
Immunology ; 142(2): 227-36, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24405357

ABSTRACT

Children with systemic Juvenile Idiopathic Arthritis (sJIA), the most severe subtype of JIA, are at risk from destructive polyarthritis and growth failure, and corticosteroids as part of conventional treatment can result in osteoporosis and growth delay. In children where there is failure or toxicity from drug therapies, disease has been successfully controlled by T-cell-depleted autologous stem cell transplantation (ASCT). At present, the immunological basis underlying remission after ASCT is unknown. Immune reconstitution of T cells, B cells, natural killer cells, natural killer T cells and monocytes, in parallel with T-cell receptor (TCR) diversity by analysis of the ß variable region (TCRVb) complementarity determining region-3 (CDR3) using spectratyping and sequencing, were studied in five children with sJIA before and after ASCT. At time of follow up (mean 11.5 years), four patients remain in complete remission, while one child relapsed within 1 month of transplant. The CD8(+) TCRVb repertoire was highly oligoclonal early in immune reconstitution and re-emergence of pre-transplant TCRVb CDR3 dominant peaks was observed after transplant in certain TCRVb families. Further, re-emergence of pre-ASCT clonal sequences in addition to new sequences was identified after transplant. These results suggest that a chimeric TCR repertoire, comprising T-cell clones developed before and after transplant, can be associated with clinical remission from severe arthritis.


Subject(s)
Arthritis, Juvenile/immunology , Hematopoietic Stem Cell Transplantation , Lymphocyte Depletion , Receptors, Antigen, T-Cell/immunology , T-Lymphocytes/immunology , Arthritis, Juvenile/therapy , Child , Clone Cells/immunology , Clone Cells/metabolism , Female , Humans , Male , T-Lymphocytes/cytology , Transplantation, Autologous
9.
Int J Sport Nutr Exerc Metab ; 23(3): 287-96, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23239679

ABSTRACT

PURPOSE: To determine whether chicken noodle soup before exercise increases ad libitum water intake, fluid balance, and physical and cognitive performance compared with water. METHODS: Nine trained men (age 25 ± 3 yr, VO2peak 54.2 ± 5.1 ml · kg-1 · min-1; M ± SD) performed cycle exercise in the heat (wet bulb globe temperature = 25.9 ± 0.4 °C) for 90 min at 50% VO2peak, 45 min after ingesting 355 ml of either commercially available bottled water (WATER) or chicken noodle soup (SOUP). The same bottled water was allowed ad libitum throughout both trials. Participants then completed a time trial to finish a given amount of work (10 min at 90% VO2peak; n = 8). Cognitive performance was evaluated by the Stroop color-word task before, every 30 min during, and immediately after the time trial. RESULTS: Ad libitum water intake throughout steady-state exercise was greater in SOUP than with WATER (1,435 ± 593 vs. 1,163 ± 427 g, respectively; p < .03). Total urine volume was similar in both trials (p = .13), resulting in a trend for greater water retention in SOUP than in WATER (87.7% ± 7.6% vs. 74.9% ± 21.7%, respectively; p = .09), possibly due to a change in free water clearance (-0.32 ± 1.22 vs. 0.51 ± 1.06 ml/min, respectively; p = .07). Fluid balance tended to be improved with SOUP (-106 ± 603 vs. -478 ± 594 g, p = .05). Likewise, change in plasma volume tended to be reduced in SOUP compared with WATER (p = .06). Only mild dehydration was achieved (<1%), and physical performance was not different between treatments (p = .77). The number of errors in the Stroop color-word task was lower in SOUP throughout the entire trial (treatment effect; p = .04). CONCLUSION: SOUP before exercise increased ad libitum water intake and may alter kidney function.


Subject(s)
Dehydration/diet therapy , Drinking , Exercise/physiology , Plasma Volume , Water-Electrolyte Balance/physiology , Adult , Beverages , Body Weight , Calcium, Dietary/administration & dosage , Calcium, Dietary/analysis , Dehydration/physiopathology , Hot Temperature , Humans , Male , Oxygen Consumption , Potassium, Dietary/administration & dosage , Potassium, Dietary/analysis , Sodium, Dietary/administration & dosage , Sodium, Dietary/analysis , Surveys and Questionnaires , Thirst/physiology , Young Adult
10.
Prev Med ; 56(2): 103-6, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23219682

ABSTRACT

OBJECTIVE: The objective of this study is to assess the association between average adult body mass index (BMI), automobile travel, and caloric intake in the US in order to predict future trends of adult obesity. METHODS: Annual BMI data (1984-2010) from the Behavioral Risk Factor Surveillance System (BRFSS), vehicle miles traveled data (1970-2009) from the Federal Highway Administration, licensed drivers data (1970-2009) from the Federal Highway Administration, and adult average daily caloric intake data (1970-2009) from the US Department of Agriculture were collected. A statistical model is proposed to capture multicollinearity across the independent variables. RESULTS: The proposed statistical model provides an estimate of changes in the average adult BMI associated with changes in automobile travel and caloric intake. According to this model, reducing daily automobile travel by one mile per driver would be associated with a 0.21 kg/m(2) reduction in the national average BMI after six years. Reducing daily caloric intake by 100 calories per person would be associated with a 0.16 kg/m(2) reduction in the national average BMI after three years. CONCLUSION: Making small changes in travel or diet choices may lead to comparable obesity interventions, implying that travel-based interventions may be as effective as dietary interventions.


Subject(s)
Automobile Driving/statistics & numerical data , Body Mass Index , Energy Intake/physiology , Obesity/epidemiology , Adult , Behavioral Risk Factor Surveillance System , Female , Food Preferences , Health Promotion/methods , Humans , Male , Models, Statistical , Obesity/prevention & control , United States/epidemiology
11.
Med Sci Sports Exerc ; 41(11): 2017-25, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19812516

ABSTRACT

PURPOSE: This article aimed to study the effect of preexercise ingestion of an electrolyte-containing beverage and meal on fluid balance during exercise in men and women. METHODS: Twenty healthy, college-aged people (10 males, 10 females; mean +/- SD = 51.2 +/- 9.8 mL x kg x min(-1)) exercised at 58 +/- 4% V O 2 peak for 90 min, 45 min after ingesting 355 mL of chicken noodle soup (SOUP; 167 mmol x L(-1) Na +), carbohydrate-electrolyte beverage (CE; 16 mmol x L(-1) Na+), or water (WATER). After 90 min of exercise, participants completed a physical performance task (PPT) consisting of the calculated work that would be completed in 30 min at 60% V O 2 peak (n = 19). Water was allowed ad libitum throughout all trials. RESULTS: Fluid balance was improved in SOUP compared with WATER (-251 +/- 418 vs -657 +/- 593 g, respectively; P = 0.002) because of greater water intake and retention throughout the trial. Water intake was also greater in CE compared with WATER mostly because of an increase during the PPT. Plasma osmolality increased after ingestion of SOUP and remained elevated throughout exercise compared with both CE and WATER. Men and women had similar fluid balance results, with women having lower relative water intake and evaporative water losses compared with men. Physical performance was similar in all trials. CONCLUSIONS: SOUP ingested before exercise improves fluid balance because of increased ad libitum water intake and reduced proportional urinary water loss. The increase in water intake and, subsequently, the improved fluid balance may be because of a greater plasma osmolality before and throughout exercise.


Subject(s)
Drinking , Energy Intake/physiology , Exercise/physiology , Water-Electrolyte Balance , Adult , Dehydration/prevention & control , Dehydration/therapy , Female , Humans , Male , Sodium/administration & dosage , Task Performance and Analysis , Young Adult
12.
Methods Mol Med ; 136: 97-116, 2007.
Article in English | MEDLINE | ID: mdl-17983143

ABSTRACT

The recognition of a wide diversity of antigens by lymphocytes is made possible by the expression of a large range of highly variable antigen specific receptors, coded for by tandem arrays of genes, which undergo rearrangement during T- and B-cell development. The study of T-cell receptor (TCR) diversity and clonal composition of mixed T-cell populations has taken advantage of the features of the TCR molecule in various ways. This chapter focuses on the study of T-cells obtained from the synovial fluid of patients with inflammatory arthritis. Methods to process and store the samples and to separate cell populations are described. Two alternative molecular methods to analyse TCR diversity, identify clonal expansions, and track specific T-cell populations over both time and location are also detailed.


Subject(s)
Cell Separation/methods , Receptors, Antigen, T-Cell/immunology , Synovial Fluid/cytology , T-Lymphocytes/chemistry , Antigens/metabolism , Child , Fetal Blood/cytology , Fetal Blood/immunology , Heteroduplex Analysis , Humans , Receptors, Antigen, T-Cell/chemistry , Receptors, Antigen, T-Cell/genetics , Synovial Fluid/immunology , T-Lymphocytes/immunology , T-Lymphocytes/physiology
13.
J Clin Invest ; 117(8): 2241-9, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17671654

ABSTRACT

We treated 10 children with X-linked SCID (SCID-X1) using gammaretrovirus-mediated gene transfer. Those with sufficient follow-up were found to have recovered substantial immunity in the absence of any serious adverse events up to 5 years after treatment. To determine the influence of vector integration on lymphoid reconstitution, we compared retroviral integration sites (RISs) from peripheral blood CD3(+) T lymphocytes of 5 patients taken between 9 and 30 months after transplantation with transduced CD34(+) progenitor cells derived from 1 further patient and 1 healthy donor. Integration occurred preferentially in gene regions on either side of transcription start sites, was clustered, and correlated with the expression level in CD34(+) progenitors during transduction. In contrast to those in CD34(+) cells, RISs recovered from engrafted CD3(+) T cells were significantly overrepresented within or near genes encoding proteins with kinase or transferase activity or involved in phosphorus metabolism. Although gross patterns of gene expression were unchanged in transduced cells, the divergence of RIS target frequency between transduced progenitor cells and post-thymic T lymphocytes indicates that vector integration influences cell survival, engraftment, or proliferation.


Subject(s)
CD3 Complex , Gammaretrovirus , Genetic Vectors , Hematopoietic Stem Cell Transplantation , T-Lymphocytes/immunology , Virus Integration , X-Linked Combined Immunodeficiency Diseases/therapy , Adult , Cell Proliferation , Cell Survival/genetics , Cell Survival/immunology , Child , Child, Preschool , Female , Follow-Up Studies , Graft Survival/genetics , Graft Survival/immunology , Hematopoietic Stem Cells/immunology , Humans , Infant , Male , Transduction, Genetic , Transplantation, Autologous , X-Linked Combined Immunodeficiency Diseases/genetics , X-Linked Combined Immunodeficiency Diseases/immunology
14.
Med Sci Sports Exerc ; 38(8): 1451-61, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16888459

ABSTRACT

Testosterone prohormones such as androstenedione, androstenediol, and dehydroepiandrosterone (DHEA) have been heavily marketed as testosterone-enhancing and muscle-building nutritional supplements for the past decade. Concerns over the safety of prohormone supplement use prompted the United States Food and Drug Administration to call for a ban on androstenedione sales, and Congress passed the Anabolic Steroid Control Act of 2004, which classifies androstenedione and 17 other steroids as controlled substances. As of January 2005, these substances cannot be sold without prescription. Here, we summarize the current scientific knowledge regarding the efficacy and safety of prohormone supplementation in humans. We focus primarily on androstenedione, but we also discuss DHEA, androstenediol, 19-nor androstenedione, and 19-nor androstenediol supplements. Contrary to marketing claims, research to date indicates that the use of prohormone nutritional supplements (DHEA, androstenedione, androstenediol, and other steroid hormone supplements) does not produce either anabolic or ergogenic effects in men. Moreover, the use of prohormone nutritional supplements may raise the risk for negative health consequences.


Subject(s)
Androstenediols/pharmacology , Androstenedione/pharmacology , Dehydroepiandrosterone/pharmacology , Doping in Sports , Androstenediols/adverse effects , Androstenedione/adverse effects , Dehydroepiandrosterone/adverse effects , Doping in Sports/legislation & jurisprudence , Drug and Narcotic Control , Humans , Substance Abuse Detection , United States
15.
Blood ; 105(11): 4255-7, 2005 Jun 01.
Article in English | MEDLINE | ID: mdl-15687233

ABSTRACT

Gene therapy has been shown to be a highly effective treatment for infants with typical X-linked severe combined immunodeficiency (SCID-X1, gammac-deficiency). For patients in whom previous allogeneic transplantation has failed, and others with attenuated disease who may present later in life, the optimal treatment strategy in the absence of human leukocyte antigen (HLA)-matched donors is unclear. Here we report the failure of gene therapy in 2 such patients, despite effective gene transfer to bone marrow CD34(+) cells, suggesting that there are intrinsic host-dependent restrictions to efficacy. In particular, there is likely to be a limitation to initiation of normal thymopoiesis, and we therefore suggest that intervention for these patients should be considered as early as possible.


Subject(s)
Genetic Diseases, X-Linked/therapy , Genetic Therapy , Severe Combined Immunodeficiency/therapy , Adult , Antigens, CD34 , Bone Marrow Cells/metabolism , Bone Marrow Transplantation , Humans , Male , Transduction, Genetic , Treatment Failure
16.
J Clin Endocrinol Metab ; 89(12): 6235-8, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15579782

ABSTRACT

Urinary steroid excretion after androstenedione intake has been examined after a single dose of 50 mg and single doses of 100 or 300 mg/d for 7 d. We evaluated the effects of 28 d of 100 mg three times a day (t.i.d.) androstenedione intake on urinary steroid excretion. Twenty healthy men, ages 30-39 yr (33.5 +/- 0.6), consumed 100 mg androstenedione t.i.d. or placebo for 28 d. Urine samples were analyzed for testosterone, epitestosterone, androsterone, and etiocholanolone via HPLC/tandem mass spectrometry on d 0 and 28. Androstenedione intake increased (P < 0.05) urinary testosterone 35.1 +/- 10.5 ng/ml vs. 251.6 +/- 87.5 ng/ml, epitestosterone 35.3 +/- 8.8 ng/ml vs. 99.7 +/- 28.7 ng/ml, androsterone 2,102 +/- 383 ng/ml vs. 15,767 +/- 3,358 ng/ml, and etiocholanolone 1,698 +/- 409 ng/ml vs. 11,329 +/- 2,656 ng/ml (means +/- se). Although the testosterone to epitestosterone ratio (T/E) tended to increase with androstenedione intake (1.2 +/- 0.3 vs. 4.0 +/- 1.6; P = 0.12), only one subject had a urinary T/E greater than the current Olympic criteria (>6.0) for a positive drug test. Chronic intake of 100 mg androstenedione t.i.d. increases the urinary excretion of steroid metabolites. Due to inconsistent increases in the T/E ratio, the T/E ratio may not effectively detect androstenedione use.


Subject(s)
Androstenedione/administration & dosage , Steroids/metabolism , Urine/chemistry , Administration, Oral , Adult , Androstenedione/pharmacology , Androsterone/urine , Diet , Double-Blind Method , Drug Administration Schedule , Epitestosterone/urine , Etiocholanolone/urine , Hormones/blood , Hormones/urine , Humans , Male , Testosterone/urine
17.
Proteomics ; 4(6): 1562-70, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15174126

ABSTRACT

The Phosphorylation Site Database [http://vigen.biochem.vt.edu/xpd/xpd.htm] provides ready access to information from the primary scientific literature concerning those proteins from prokaryotic organisms, i.e., the members of the domains Archaea and Bacteria, that have been reported to undergo covalent phosphorylation on the hydroxyl side chains of serine, threonine, and/or tyrosine residues. Where known, the sequence of the site(s) of phosphorylation and the functional consequences of phosphorylation also are included. Active links enable users to quickly access further information concerning the phosphoprotein of interest from PubMed, GenBank, SWISS-PROT, and PIR.


Subject(s)
Databases, Factual , Phosphoproteins/chemistry , Prokaryotic Cells/metabolism , Serine/metabolism , Threonine/metabolism , Tyrosine/metabolism , Archaea/chemistry , Bacteria/chemistry , Internet , Phosphoproteins/metabolism
18.
Br J Haematol ; 123(4): 712-9, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14616977

ABSTRACT

Retroviral vectors encoding the herpes simplex thymidine kinase gene have been used to render T cells sensitive to the prodrug ganciclovir. Such genetically modified T cells have been used in clinical trials for their graft-versus-leukaemia effects following allogeneic haematopoietic stem cell transplantation. In the event of graft-versus-host disease (GVHD) the cells were susceptible to elimination through exposure to ganciclovir. We have investigated the impact of T-cell activation, required for successful retrovirus-mediated gene transfer, on T-cell receptor repertoire profile, subset distribution and antiviral potential. Using a combination of antibodies against CD3 and CD28, T cells were transduced at high efficiency when exposed to retrovirus between 48 and 72 h later. Lymphocytes had undergone up to seven cycles of cell division by the end of the procedure. Although the T-cell receptor Vbeta repertoire was not altered after retroviral transduction, there were notable shifts in subset profiles with an increased proportion of CD45RO cells in transduced populations. T cells continued to proliferate for several days after transduction and were difficult to sustain under the extended culture conditions required to generate virus-specific T cells. These observations may explain the lower than expected levels of GVHD and poor antiviral immunity reported in recent trials.


Subject(s)
Genetic Therapy/methods , Genetic Vectors/administration & dosage , Retroviridae/genetics , Simplexvirus/enzymology , T-Lymphocytes/virology , Thymidine Kinase/genetics , Animals , Antiviral Agents/therapeutic use , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Immunoglobulin Variable Region/analysis , Mice , Receptors, Antigen, T-Cell, alpha-beta/analysis , T-Lymphocytes/immunology , T-Lymphocytes/transplantation , Transduction, Genetic/methods
19.
Menopause ; 10(4): 322-31, 2003.
Article in English | MEDLINE | ID: mdl-12851515

ABSTRACT

OBJECTIVE: Menopause-induced estrogen deficiency increases the risk of cardiovascular disease, which is related to a shift in regional fat distribution. We tested the hypothesis that estrogen-like isoflavones in soy protein isolate (SPI+) would lessen both regional fat gain and lean loss compared with isoflavone-poor soy (SPI-). DESIGN: Perimenopausal participants (N = 69) were randomly assigned (double-blind) to 24 weeks of treatment (40 g soy or whey protein per day): SPI+ (n = 24), SPI- (n = 24), or whey control (n = 21); each participant had blood drawn in the fasted (12 hours) state, had physical activity assessed, and kept a 5-day food diary. Dual-energy x-ray absorptiometry was used to examine the effects of SPI+ on regional fat and lean tissue distribution changes in the waist, hip, and thigh regions. RESULTS: Mean body mass increased (P < 0.01) in each group, but treatment had no effect on gain in overall body mass, fat mass, or lean mass using analysis of variance. In all treatment groups combined, lean mass increased in each region; fat mass increased only in the waist region. Treatment had an effect (P = 0.039) on hip lean mass and a marginal effect (P = 0.077) on thigh fat. Regression analyses revealed that SPI+ diminished the increase in thigh fat (P = 0.018) and heightened the increase in hip lean (P = 0.035) mass. Carbohydrate intake (P = 0.006) and cohort (reflective of season; P = 0.011) contributed to the gain in thigh fat. Total protein intake (P = 0.0012), plasma insulin (P = 0.0034), and physical activity (P = 0.047) contributed to the gain in hip lean mass. CONCLUSIONS: Gain in hip lean mass was greater (P = 0.014) in SPI+ than other groups, but SPI+ did not reduce the disease-promoting menopausal shift in regional fat mass.


Subject(s)
Adipose Tissue/drug effects , Body Composition/drug effects , Body Constitution , Climacteric , Isoflavones/pharmacology , Soybean Proteins/pharmacology , Analysis of Variance , Double-Blind Method , Female , Humans , Middle Aged , Patient Compliance , Regression Analysis
20.
J Appl Physiol (1985) ; 92(1): 142-6, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11744653

ABSTRACT

The effectiveness of orally ingested androstenediol in raising serum testosterone concentrations may be limited because of hepatic breakdown of the ingested androgens. Because androstenediol administered sublingually with cyclodextrin bypasses first-pass hepatic catabolism, we evaluated the acute hormonal response to sublingual cyclodextrin androstenediol supplement in young men. Eight men (22.9 +/- 1.2 yr) experienced in strength training consumed either 20 mg androstenediol in a sublingual cyclodextrin tablet (Sl Diol) or placebo (Pl) separated by at least 1 wk in a randomized, double-blind, crossover manner. Blood samples were collected before supplementation and at 30-min intervals for 3 h after supplementation. Serum hormone concentrations did not change with Pl. Serum androstenedione concentrations were increased (P < 0.05) above baseline (11.2 +/- 1.1 nmol/l) with Sl Diol from 60 to 180 min after intake and reached a peak concentration of 25.2 +/- 2.9 nmol/l at 120 min. Serum free testosterone concentrations were increased from 86.2 +/- 9.1 pmol/l with Sl Diol from 30 to 180 min and reached a peak concentration of 175.4 +/- 12.2 pmol/l at 60 min. Serum total testosterone concentrations increased above basal (25.6 +/- 2.3 nmol/l) from 30 to 180 min with Sl Diol and reached a peak concentration of 47.9 + 2.9 nmol/l at 60 min. Serum estradiol concentrations were elevated (P < 0.05) above baseline (0.08 +/- 0.01 nmol/l) from 30 to 180 min with Sl Diol and reached 0.14 +/- 0.02 nmol/l at 180 min. These data indicate that sublingual cyclodextrin androstenediol intake increases serum androstenedione, free testosterone, total testosterone, and estradiol concentrations.


Subject(s)
Androstenediol/pharmacology , Hormones/blood , Administration, Sublingual , Adult , Androstenediol/administration & dosage , Androstenediol/blood , Body Composition/drug effects , Cyclodextrins , Diet , Estradiol/blood , Excipients , Humans , Male , Testosterone/blood , Weight Lifting
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