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1.
Res Q Exerc Sport ; 94(4): 1169-1182, 2023 Dec.
Article in English | MEDLINE | ID: mdl-36624961

ABSTRACT

Purpose: Following increased interest in physical literacy (PL), development of appropriate tools for assessment has become an important next step for its operationalization. To forward the development of such tools, the objective of this study was to build the foundations of the Évaluation de la Littératie Physique (ELIP), designed to help reduce existing tensions in approaches to PL assessment that may be resulting in a low uptake into applied settings. Methods: We followed two steps: (1) the development of the first version of ELIP by deploying a Delphi method (n = 30); and (2) the modification of items through cognitive interviews with emerging adults (n = 32). Results: The expert consensus highlighted four dimensions of PL to be assessed-physical; affective; cognitive; and social-with new perspectives, including a preference for broad motor tests over fitness. Conclusion: Results offer new insights into the assessment of emerging adults' PL, but ELIP still requires further work concerning validity, reliability, and sensitivity.


Subject(s)
Health Literacy , Humans , Adult , Reproducibility of Results , Exercise
2.
J Med Case Rep ; 16(1): 167, 2022 Apr 21.
Article in English | MEDLINE | ID: mdl-35449024

ABSTRACT

BACKGROUND: Retinal arterial occlusive events in young patients are rare. However, because of physiological multifactorial adaptations during pregnancy, retinal vascular occlusive disease may occur spontaneously. In addition, a patent foramen ovale is a risk factor for an ischemic thromboembolic event. Since fluorescein angiography, a central tool in the evaluation of these occlusions, should be avoided during pregnancy, optical coherence tomography angiography, a novel technique, offers a good opportunity for visualizing vascular perfusion of retinal tissue. CASE PRESENTATION: Here we present a case series of three patients (Caucasian, nonsmoker) who visited our clinic owing to acute visual impairment and central scotoma. Using regular optical coherence tomography and optical coherence tomography angiography, retinal vascular occlusions were detected, thus initiating the evaluation of systemic risk factors. We report two patients (30 and 32 years old) who developed cilioretinal artery occlusion but whose etiology differed: one was of thromboembolic origin associated with patent foramen ovale, while the other was caused by hemodynamic blockade secondary to central retinal vein occlusion. In both cases, optical coherence tomography angiography revealed reperfusion of the cilioretinal artery occlusion. However, transient ischemia led to retinal atrophy after a few weeks. In the third patient (32 years old), 8 weeks after onset of scotoma, optical coherence tomography angiography revealed atrophy of the middle layers and impaired perfusion in the deep capillary plexus, and thus a paracentral acute middle maculopathy was diagnosed. All patients regained normal visual acuity and had otherwise uncomplicated pregnancies, and laboratory blood tests did not reveal any defects or alterations. CONCLUSIONS: As shown here, optical coherence tomography angiography enables risk-free imaging of retinal vessel perfusion during pregnancy. Together with regular optical coherence tomography, it allows one to predict functional outcome according to the existing retinal occlusion-related atrophy.


Subject(s)
Foramen Ovale, Patent , Retinal Artery Occlusion , Retinal Diseases , Adult , Atrophy/complications , Atrophy/pathology , Female , Fluorescein Angiography/methods , Foramen Ovale, Patent/complications , Humans , Ischemia/diagnosis , Pregnancy , Retinal Artery Occlusion/diagnostic imaging , Retinal Artery Occlusion/etiology , Retinal Diseases/etiology , Retinal Vessels/pathology , Scotoma , Tomography, Optical Coherence/methods
3.
Ophthalmologe ; 117(9): 914-916, 2020 Sep.
Article in German | MEDLINE | ID: mdl-31745648

ABSTRACT

Penetrating eye injuries often lead to serious symptoms, such as severe inflammation and pain, especially if residual intraocular foreign bodies are present. This case report describes a patient who suffered a penetrating corneal injury resulting in eyelashes being displaced into the anterior chamber. Although no treatment was given the anterior chamber of the eye did not show any inflammatory reactions 2 weeks after the trauma. In addition to the accident mechanism the material of which the foreign body is composed plays a decisive role. While iron, copper and wooden foreign bodies lead to severe intraocular inflammation, keratin is immunologically well-tolerated.


Subject(s)
Corneal Injuries , Eye Foreign Bodies , Eye Injuries, Penetrating , Eyelashes , Anterior Chamber , Cornea , Humans
4.
J Eur Acad Dermatol Venereol ; 33(2): 398-404, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30357954

ABSTRACT

BACKGROUND: Although chronic pruritus affects a large part of the population, its reliable assessment remains difficult. Electronical diaries (eDiaries) are often used in multicentre clinical trials. The ItchApp© for Android was developed to assess itch intensity and course and was validated for the German language in 2017. OBJECTIVE: To validate ItchApp© for the use in the Polish and US English languages. METHODS: Fifty-three subjects in Poland and thirty subjects in the USA with chronic pruritus completed the paper-based and app-based questionnaires. These questionnaires contained items for measuring the itch intensity, including a numerical rating scale (NRS) and verbal rating scale (VRS), and for detecting the change of pruritus since the beginning of treatment. RESULTS: The ItchApp© showed a high level of test-retest reliability [Intraclass correlation, Kappa and Kendall-Tau B coefficients: 0.915-1.000 (Poland) and 0.863-1.000 (USA)]. The convergent validity showed strong correlation between the itch intensity scales on the ItchApp© (Items II-IV = VRS mean, NRS mean and NRS worst) and the paper-based itch intensity scales (mean and worst: VRS, NRS, VAS) [Spearman-Rho and Pearson correlation coefficients: 0.710-0.987 (Poland) and 0.646-0.954 (USA)]. The ItchApp© items moderately correlated with the ItchyQol scores [Spearman-Rho and Pearson correlation coefficients: 0.303-0.554 (Poland) and 0.275-0.447 (USA)]. After completing the ItchApp© questionnaire, a feasibility questionnaire was completed and showed that subjects feel the app is well suited for assessing pruritus. CONCLUSION: We provide evidence for the ItchApp© as a validated eDiary for the assessment of pruritus in Polish and US English languages, enabling its use in multicentre international clinical trials.


Subject(s)
Diagnosis, Computer-Assisted/methods , Medical Records , Mobile Applications/standards , Pruritus/diagnosis , Adult , Age Factors , Aged , Female , Humans , Male , Middle Aged , Mobile Applications/statistics & numerical data , Poland , Risk Assessment , Sampling Studies , Sensitivity and Specificity , Severity of Illness Index , Sex Factors , Surveys and Questionnaires , United States , Young Adult
5.
Scand J Med Sci Sports ; 28(3): 928-938, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29059478

ABSTRACT

Aquatic survival skills may be compromised in cold water thereby increasing the likelihood of drowning. This study compared physiological, psychological, and behavioral responses of humans treading water and swimming in cold and temperate water. Thirty-eight participants were classified as inexperienced (n = 9), recreational (n = 15), or skilled (n = 10) swimmers. They performed 3 tasks: treading water (120 seconds), swim at "comfortable" pace, and swim at "fast" pace in 2 water conditions (28°C vs 10°C). Heart rate, oxygen uptake, psychometric variables, spatio-temporal (swim speed, stroke rate, and stroke length), and coordination type were examined as a function of expertise. Tasks performed in cold water-generated higher cardiorespiratory responses (HR = 145 ± 16 vs 127 ± 21 bpm) and were perceived about 2 points more strenuous on the Borg scale on average (RPE = 14.9 ± 2.8 vs 13.0 ± 2.0). The voluntary durations of both treading water (60 ± 32 vs 91 ± 33 seconds) and swimming at a comfortable pace (66 ± 22 vs 103 ± 34 seconds) were significantly reduced in cold water. However, no systematic changes in movement pattern type could be determined in either the treading water task or the swimming tasks. Water temperature influences the physical demands of these aquatic skills but not necessarily the behavior. Training treading water and swimming skills in temperate water seems to transfer to cold water, but we recommend training these skills in a range of water conditions to help adapt to the initial "cold-shock" response.


Subject(s)
Cold Temperature , Physical Exertion , Swimming/physiology , Swimming/psychology , Adolescent , Adult , Cold-Shock Response , Female , Heart Rate , Humans , Male , Oxygen Consumption , Psychometrics , Temperature , Water , Young Adult
6.
Opt Lett ; 36(13): 2456-8, 2011 Jul 01.
Article in English | MEDLINE | ID: mdl-21725443

ABSTRACT

We report on a Yb:YAG Innoslab laser amplifier system for generation of subpicsecond high energy pump pulses for optical parametric chirped pulse amplification (OPCPA) at high repetition rates. Pulse energies of up to 20 mJ (at 12.5 kHz) and repetition rates of up to 100 kHz were attained with pulse durations of 830 fs and average power in excess of 200 W. We further investigate the possibility to use subpicosecond pulses to derive a stable continuum in a YAG crystal for OPCPA seeding.

7.
Int J Sports Med ; 31(12): 875-81, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21072734

ABSTRACT

The hip intracyclic velocity variability and the index of coordination in front crawl swimming were examined in relation to performance level. 22 swimmers were assigned to either an elite or a recreational swimming group and performed 4 swim trials at different paces relative to their individual maximum velocity. A velocity meter system was set to determine intracyclic velocity variability and video analysis allowed the determination of the index of coordination. Mean intracyclic velocity variability was lower in the elite swimmers than the recreational swimmers (14.39 ± 1.97 vs. 17.80 ± 4.23%, p<0.05), and remained stable with swim pace (i. e., the relative velocity) for the elite group, whereas it increased for the recreational group (p<0.05). The elite swimmers were characterized by a lower mean index of coordination than the recreational swimmers (-9.6 ± 7.1 vs. -6.9 ± 5.0%, p<0.05), but it increased with swim velocity in the elite group and showed only a tendency in the recreational group (p=0.07). These findings suggest that low intracyclic velocity variability and its stability over a range of swimming paces, which result from optimized inter-arm coordination, are characteristic of skilled performance. Thus, the examination of intracyclic velocity variability and index of coordination variability with different swim paces could provide new insight into skilled performance in swimming.


Subject(s)
Arm/physiology , Athletic Performance/physiology , Hip/physiology , Swimming/physiology , Adolescent , Adult , Athletes , Biomechanical Phenomena , Humans , Male , Video Recording , Young Adult
8.
Hum Mov Sci ; 29(3): 426-39, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20430465

ABSTRACT

The effects of skill level on index of arm coordination (IdC), mechanical power output (P(d)), and swim efficiency were studied in front crawlers swimming at different speeds. Seven national and seven regional swimmers performed an arms-only intermittent graded speed test on the MAD-system and in a free condition. The MAD-system measured the drag (D) and P(d). Swimming speed (v), stroke rate (SR), stroke length (SL), stroke index (SI), relative entry, pull, push, and recovery phase durations, and IdC were calculated. Swim efficiency was assessed from SI, the coefficient of variation of calculated hip intra-cyclic velocity variations (IVV), and the efficiency of propulsion generation, i.e., the ratio of v(2) to tangential hand speed squared (u(2)). Both groups increased propulsive continuity (IdC) and hand speed (u) and applied greater P(d) to overcome active drag with speed increases (p<.05). This motor organization adaptation was adequate because SI, IVV, and v(2)/u(2) were unchanged. National swimmers appeared more efficient, with greater propulsive continuity (IdC) and P(d) to reach higher v than regional swimmers (p<.05). The regional swimmers exhibited a higher u and lower SI, IVV, and v(2)/u(2) compared to national swimmers (p<.05), which revealed lower effectiveness to generate propulsion, suggesting that technique is a major determinant of swimming performance.


Subject(s)
Arm/physiology , Power, Psychological , Psychomotor Performance/physiology , Swimming , Adaptation, Physiological/physiology , Biomechanical Phenomena/physiology , Body Mass Index , Humans , Male , Models, Biological , Movement/physiology , Videotape Recording , Young Adult
9.
Bone ; 44(4): 603-11, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19136082

ABSTRACT

UNLABELLED: Fragility fracture rates in South Africa are lower in blacks (B) than in whites (W) both in adults and in children. In adults this difference may in part be explained by histomorphometric findings in iliac crest cortical bone of B of thicker, less porous cortices, greater endocortical (Ec) wall thickness, fewer canals and greater osteoid thickness accompanied by greater mineral apposition rate and bone formation rate compared to W. Since no comparative data for B and W children are available we examined iliac crest cortical bone of 57 B and 56 W aged 0-23 yrs by routine histomorphometry. RESULTS: The effects of growth as expressed in differences between external and internal cortex were similar in B and W children. Cortical thickness increased with age similarly in B and W until about age 15 whereafter it continued to increase only in B. Ec wall thickness rose with age in B but did not change in W. After age 11 canal number was lower in B. Cortical porosity was highest between ages 6 and 15 with a tendency to lower values in the external cortex in B. Thus structural differences reported in adults were evident in children. Bone turnover as reflected in osteoid surface and eroded surface declined with age similarly in B and W but osteoid thickness did not change with age. Greater osteoid thickness in B children could reflect greater vigor of osteoblasts and greater osteoblast team performance as it did in B adults and may have contributed to the structural advantage in B children. CONCLUSION: B children showed greater values for osteoid thickness, endocortical wall thickness and cortical thickness, and a tendency to lower porosity compared to W children. These features may contribute to lower fragility fracture rates in B children. Differing environmental influences and possibly genetic effects may play a role.


Subject(s)
Black People/ethnology , Bone Development/physiology , Bone and Bones/anatomy & histology , Bone and Bones/physiology , White People/ethnology , Adolescent , Adult , Bone Remodeling , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Infant , Infant, Newborn , Male , South Africa
10.
Int J Sports Med ; 29(6): 480-6, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18027306

ABSTRACT

The link between modifications in arm coordination (IdC) and intracyclic velocity variation (IVV) as a function of swim pace and gender is investigated. Twelve elite swimmers performed 5 different swim paces. Video analysis allowed IdC determination. The IVV was determined with a velocity-metre system. Results showed (i) a significant increase in IdC with swim pace (p < 0.05) but no significant change in IVV, and (ii) a gender effect for the mean values of both IdC and IVV (p < 0.05). This suggests that (i) the increase in IdC with swimming velocity helps to maintain IVV stability, and (ii) the mean IdC and the IVV level are determined by the relationship between anthropometric parameters and mechanical power output. Indeed, compared to males, the females generally had a lower mechanical power output, and lower drag to overcome, which explains the lower IVV found. It was concluded that increasing IdC could be a strategy adopted by elite swimmers to maintain IVV at a constant level, despite increases in both propulsive and drag forces and in relation to individual characteristics. Thus, the IVV-IdC relationship may be an interesting tool to determine a swimmer's misadaptation to the swim pace and to orient individual coaching in coordination analysis.


Subject(s)
Adaptation, Physiological/physiology , Arm/physiology , Swimming/physiology , Anthropometry , Female , France , Humans , Male , Sex Factors , Videotape Recording
11.
J Cell Mol Med ; 11(4): 852-67, 2007.
Article in English | MEDLINE | ID: mdl-17760845

ABSTRACT

To develop a non-human primate model of systemic bone loss after ovariectomy, 24 ovariectomized (OVX) and eight control (non-OVX) female baboons Papio ursinus were investigated over a period of 48 months using bone mineral density (BMD), iliac crest bone histomorphometry, bone turnover markers, and variables of calcium metabolism. Lumbar spine (L1-L4) BMD measured by dual energy X-ray absorptiometry (DXA) decreased in OVX animals in the first 12 months (-7.6%) and showed a slow trend towards recovery after 24 months. Controls showed a slow increase in spinal BMD over 4 years (+9.7%). Total hip BMD decreased slowly up to 48 months in all animals (OVX -12.6%versus controls -10%); this indicated that OVX had a limited effect on total hip BMD. Forearm BMD did not change. The significant decrease in trabecular bone volume (TBV) of the iliac crest from baseline to 12 months was followed by some recovery. Microarchitectural deterioration of trabecular bone in OVX animals was demonstrated by a decline in trabecular number and an increase in trabecular spacing. These changes were also evident on sections of whole vertebrae, proximal femora and iliac crests. Changes in iliac TBV reflected spinal but not hip BMD changes in the OVX animals. Static and dynamic histomorphometric variables indicated that bone turnover was increased for 36 months following OVX. Controls showed no changes in histomorphometric variables. Bone specific alkaline phosphatase (ALPs) in OVX animals remained elevated throughout the study; osteocalcin (OC) was significantly elevated only at 6 and 12 months, and deoxypyridinoline (Pyr-D) was elevated at 12 months but declined after 24 months. ALPs was thus more sensitive to the long-term effects of OVX than were OC or Pyr-D. Controls showed no changes in bone turnover markers. This study showed consistent deleterious changes in lumbar BMD, bone histomorphometry with microarchitectural deterioration together with altered biochemical markers of bone turnover in the first 12 months after OVX. Since these changes resemble those in post-menopausal women, the non-human primate Papio ursinus is suitable for the study of bone loss in post-menopausal women.


Subject(s)
Bone Resorption/pathology , Ovary/surgery , Absorptiometry, Photon , Alkaline Phosphatase/blood , Amino Acids/urine , Animals , Biomarkers , Bone Density , Bone Resorption/physiopathology , Calcium/urine , Female , Humans , Ilium/pathology , Lumbar Vertebrae/pathology , Osteocalcin/blood , Papio , Pelvimetry , Phosphates/urine
12.
Int J Sports Med ; 28(2): 164-71, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17024620

ABSTRACT

Spatio-temporal, metabolic and psychometric responses during and after a 400-m freestyle swim trial were investigated for gender and skill-level effects. Thirty-four men and women, 18 national and international competitors and 16 recreational swimmers, were compared. Mean speed, stroke rate (SR), and stroke length (SL) were obtained from video recordings. Peak heart rate (HR) and the lactate value (Hla) were determined, as were the recovery kinetics, i.e., the recovery time index (RTI) for heart rate and %Hla (r) for the lactate values. Well-being was assessed with the Profile of Mood States questionnaire (POMS). Subjective workload was assessed with the NASA-TLX questionnaire. The experts showed less variation in their swim speed than the recreational swimmers. The male experts showed greater SL and the female experts showed greater SL and SR. No significant difference was noted between the experts and recreational swimmers for peaks of HR and Hla, POMS (157.3 +/- 15.1 vs. 163.1 +/- 21.5), or subjective workload (32.4 +/- 6.7 vs. 31.6 +/- 6.1). The experts exhibited higher RTI (- 38.5 +/- 5.5 % vs. - 31.1 +/- 5.4 %) and %Hla (r) (8.6 +/- 7.18 % vs. 1.65 +/- 8.2 %). They also showed an improvement of 7.8 +/- 2.6 % for men and 6.02 +/- 1.6 % for women between the performance time for the trial and the best competitive time of the season. Last, our results suggest that the 400-m freestyle trial is a valid field test to evaluate the maximal aerobic speed (MAS) of swimmers with different training status. The systemic analysis herein described can be used to set the end-of-season target time for expert competitors. Attention should focus on SL, race management, and the physiological recovery for training prescription.


Subject(s)
Swimming/physiology , Adult , Affect/physiology , Female , Heart Rate/physiology , Humans , Lactic Acid/blood , Male , Psychometrics , Recovery of Function/physiology , Sex Factors , Surveys and Questionnaires , Video Recording
13.
Calcif Tissue Int ; 79(6): 373-82, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17160576

ABSTRACT

Fragility fracture rates in South African blacks (B) are lower than in whites (W). Since bone strength in many parts of the skeleton depends mainly on cortical bone, we examined iliac crest cortical bone from 97 B (49 male, 48 female) aged 22-80 and 111 W (60 male, 51 female) aged 21-84 histomorphometrically for differences between B and W and effects of age. B had thicker (P = 0.02) and less porous (P = 0.0007) cortices, fewer haversian (H) osteons (P < 0.0001), and greater endocortical (Ec) wall thickness (P < 0.0001). B also had thicker H (P = 0.0005) and Ec osteoid seams (P < 0.0001); greater Ec osteoid surface (P = 0.0005), Ec mineral apposition rate (P < 0.0001), and Ec bone formation rate (P = 0.038); and lower H (P = 0.0002) and Ec eroded surfaces (P = 0.029). Some of the differences were already present in subjects aged 21-30 years. Although cortical structure deteriorated with age in B and W, after age 40 Ec wall thickness declined only in W. Greater Ec mineral apposition and bone formation rates, i.e., greater osteoblast efficiency at the cellular and tissue levels, suggest better Ec bone preservation that may contribute to lower fragility fracture rates in B.


Subject(s)
Black People , Ilium/anatomy & histology , White People , Adult , Age Factors , Aged , Aged, 80 and over , Biomarkers/metabolism , Bone Density , Bone Remodeling/drug effects , Bone Remodeling/physiology , Cross-Sectional Studies , Demeclocycline , Female , Humans , Ilium/drug effects , Ilium/metabolism , Male , Middle Aged , Reference Values , Sex Factors , Tetracycline
14.
Calcif Tissue Int ; 76(2): 79-89, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15549637

ABSTRACT

Osteoporosis and femoral neck fractures (FNF) are uncommon in black Africans although osteoporosis accompanying iron overload (from traditional beer brewed in iron containers) associated with ascorbic acid deficiency (oxidative catabolism by iron) has been described from sub-Saharan Africa. This study describes histomorphometric findings of iliac crest bone biopsies and serum biochemical markers of iron overload and of alcohol abuse and ascorbic acid levels in 50 black patients with FNFs (29 M, 21 F), age 62 years (40-95) years (median [min-max]), and in age- and gender-matched black controls. We found evidence of iron overload in 88% of patients and elevated markers of alcohol abuse in 72%. Significant correlations between markers of iron overload and of alcohol abuse reflect a close association between the two toxins. Patients had higher levels of iron markers, i.e., siderin deposits in bone marrow (P < 0.0001), chemical non-heme bone iron (P = 0.012), and serum ferritin (P = 0.017) than controls did. Leukocyte ascorbic acid levels were lower (P = 0.0008) than in controls. The alcohol marker mean red blood cell volume was elevated (P = 0.002) but not liver enzymes or uric acid. Bone volume, trabecular thickness, and trabecular number were lower, and trabecular separation was greater in patients than in controls, all at P < 0.0005; volume, surface, and thickness of osteoid were lower and eroded surface was greater, all at P < 0.0001. There was no osteomalacia. Ascorbic acid deficiency accounted significantly for decrease in bone volume and trabecular number, and increase in trabecular separation, osteoid surface, and eroded surface; iron overload accounted for a reduction in mineral apposition rate. Alcohol markers correlated negatively with osteoblast surface and positively with eroded surface. Relative to reported data in white FNF patients, the osteoporosis was more severe, showed lower osteoid variables and greater eroded surface; FNFs occurred 12 years earlier and were more common among men. We conclude that the osteoporosis underlying FNFs in black Africans is severe, with marked uncoupling of resorption and formation in favor of resorption. All three factors--ascorbic acid deficiency, iron overload, and alcohol abuse--contributed to the osteoporosis, in that order.


Subject(s)
Alcoholism/complications , Ascorbic Acid Deficiency/complications , Black People , Femoral Neck Fractures , Femoral Neck Fractures/etiology , Iron Overload/complications , Osteoporosis/etiology , Adult , Aged , Aged, 80 and over , Alcoholism/blood , Ascorbic Acid/metabolism , Ascorbic Acid Deficiency/blood , Biomarkers/metabolism , Bone Marrow/metabolism , Bone Marrow/pathology , Female , Femoral Neck Fractures/blood , Femoral Neck Fractures/pathology , Humans , Ilium/pathology , Iron Overload/blood , Leukocytes/metabolism , Leukocytes/pathology , Male , Middle Aged , Osteoporosis/blood , Osteoporosis/pathology , Siderosis/complications , Siderosis/metabolism , Siderosis/pathology
15.
Gut ; 52(4): 580-5, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12631673

ABSTRACT

BACKGROUND AND AIMS: In chronic liver disease, bone disease frequently develops. The contributions of the different features of liver disease such as parenchymal inflammation, portal hypertension, and portasystemic shunting on bone metabolism have not been systematically studied. The aim of this study was to identify the features of liver disease contributing to bone disease using rat models. METHODS: Parenchymal liver disease was induced by carbon tetrachloride administration, portal hypertension by partial portal vein ligation, and portasystemic shunting by end to side anastomosis of the portal vein to the inferior vena cava. Normal and sham operated surgical animals served as controls. Serum calcium, 25-hydroxy vitamin D (25-OH vit D), and osteocalcin levels, and urinary deoxypyridinoline excretion were analysed. Testosterone and oestradiol levels were determined in male and female rats, respectively. Interleukin 1, interleukin 6, and tumour necrosis factor alpha (TNF-alpha) were determined in serum. Bone density was measured in all groups and in addition, in the surgical groups, histomorphometry was performed on undecalcified specimens of the proximal tibia. The calcium content of the femurs, removed at termination and ashed, was determined. RESULTS: Early parenchymal disease and portal hypertension did not affect bone metabolism or body mass. Portasystemic shunting increased bone resorption, decreased bone formation, bone density, and trabecular bone volume which were commensurate with a reduction in body mass. TNF-alpha levels were elevated and testosterone levels were low in male portasystemic shunted rats. CONCLUSIONS: Portasystemic shunting in the rat adversely affects bone metabolism as part of a generalised catabolic state where high TNF-alpha and low testosterone and 25-OH vit D levels may play a role.


Subject(s)
Hypertension, Portal/complications , Liver Cirrhosis, Experimental/complications , Osteoporosis/etiology , Portasystemic Shunt, Surgical/adverse effects , Absorptiometry, Photon , Animals , Bone Density , Carbon Tetrachloride , Disease Models, Animal , Female , Liver Cirrhosis, Experimental/chemically induced , Male , Rats , Rats, Sprague-Dawley , Tibia/physiopathology , Tumor Necrosis Factor-alpha/metabolism
16.
J Exp Med ; 193(9): 1059-66, 2001 May 07.
Article in English | MEDLINE | ID: mdl-11342590

ABSTRACT

The complement anaphylatoxin C5a and its seven-transmembrane segment (7TMS) receptor play an important role in host defense and in a number of inflammation-associated pathologies. The NH(2)-terminal domain of the C5a receptor (C5aR/CD88) contributes substantially to its ability to bind C5a. Here we show that the tyrosines at positions 11 and 14 of the C5aR are posttranslationally modified by the addition of sulfate groups. The sulfate moieties of each of these tyrosines are critical to the ability of the C5aR to bind C5a and to mobilize calcium. A C5aR variant lacking these sulfate moieties efficiently mobilized calcium in response to a small peptide agonist, but not to C5a, consistent with a two-site model of ligand association in which the tyrosine-sulfated region of the C5aR mediates the initial docking interaction. A peptide based on the NH(2) terminus of the C5aR and sulfated at these two tyrosines, but not its unsulfated analogue or a doubly sulfated control peptide, partially inhibited C5a association with its receptor. These observations clarify structural and mutagenic studies of the C5a/C5aR association and suggest that related 7TMS receptors are also modified by functionally important sulfate groups on their NH(2)-terminal tyrosines.


Subject(s)
Antigens, CD/metabolism , Complement C5a/metabolism , Protein Processing, Post-Translational , Receptors, Complement/metabolism , Sulfates/metabolism , Tyrosine/metabolism , Amino Acid Sequence , Binding Sites , Calcium/metabolism , Cell Line, Transformed , Humans , Molecular Sequence Data , Peptides/metabolism , Receptor, Anaphylatoxin C5a
17.
Proc Natl Acad Sci U S A ; 97(17): 9712-7, 2000 Aug 15.
Article in English | MEDLINE | ID: mdl-10931940

ABSTRACT

Production of amyloid-beta protein (Abeta) is initiated by a beta-secretase that cleaves the Abeta precursor protein (APP) at the N terminus of Abeta (the beta site). A recently identified aspartyl protease, BACE, cleaves the beta site and at residue 11 within the Abeta region of APP. Here we show that BACE2, a BACE homolog, cleaves at the beta site and more efficiently at a different site within Abeta. The Flemish missense mutation of APP, implicated in a form of familial Alzheimer's disease, is adjacent to this latter site and markedly increases Abeta production by BACE2 but not by BACE. BACE and BACE2 respond identically to conservative beta-site mutations, and alteration of a common active site Arg inhibits beta-site cleavage but not cleavage within Abeta by both enzymes. These data suggest that BACE2 contributes to Abeta production in individuals bearing the Flemish mutation, and that selective inhibition of these highly similar proteases may be feasible and therapeutically advantageous.


Subject(s)
Amyloid beta-Protein Precursor/metabolism , Aspartic Acid Endopeptidases/metabolism , Protein Processing, Post-Translational , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Amino Acid Sequence , Amino Acid Substitution/genetics , Amyloid Precursor Protein Secretases , Amyloid beta-Peptides/chemistry , Amyloid beta-Peptides/genetics , Amyloid beta-Peptides/metabolism , Amyloid beta-Protein Precursor/chemistry , Amyloid beta-Protein Precursor/genetics , Arginine/genetics , Arginine/metabolism , Aspartic Acid Endopeptidases/chemistry , Aspartic Acid Endopeptidases/genetics , Binding Sites , Cell Line , Cloning, Molecular , Endopeptidases , Gene Expression Profiling , Humans , Hydrogen-Ion Concentration , Molecular Sequence Data , Mutation, Missense/genetics , Nervous System/enzymology , Netherlands , Peptide Fragments/chemistry , Peptide Fragments/genetics , Peptide Fragments/metabolism , Phenylalanine/metabolism , RNA, Messenger/analysis , RNA, Messenger/genetics , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Sequence Homology, Amino Acid , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Substrate Specificity , Sweden
18.
J Biol Chem ; 275(43): 33516-21, 2000 Oct 27.
Article in English | MEDLINE | ID: mdl-10938094

ABSTRACT

The sequential association of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 with CD4 and a seven-transmembrane segment coreceptor such as CCR5 or CXCR4 initiates entry of the virus into its target cell. The N terminus of CCR5, which contains several sulfated tyrosines, plays a critical role in the CD4-dependent association of gp120 with CCR5 and in viral entry. Here we demonstrate that a tyrosine-sulfated peptide based on the N terminus of CCR5, but not its unsulfated analogue, inhibits infection of macrophages and peripheral blood mononuclear cells by CCR5-dependent, but not CXCR4-dependent, HIV-1 isolates. The sulfated peptide also inhibited the association of CCR5-expressing cells with gp120-soluble CD4 complexes and, less efficiently, with MIP-1alpha. Moreover, this peptide inhibited the precipitation of gp120 by 48d and 23e antibodies, which recognize CD4-inducible gp120 epitopes, but not by several other antibodies that recognize proximal epitopes. The ability of the sulfated peptide to block 48d association with gp120 was dependent in part on seven tropism-determining residues in the third variable (V3) and fourth conserved (C4) domains of gp120. These data underscore the important role of the N-terminal sulfate moieties of CCR5 in the entry of R5 HIV-1 isolates and localize a critical contact between gp120 and CCR5.


Subject(s)
Antiviral Agents/pharmacology , CD4 Antigens/metabolism , HIV Envelope Protein gp120/metabolism , HIV-1/drug effects , Receptors, CCR5/physiology , Amino Acid Sequence , Animals , Binding Sites , Cells, Cultured , Dogs , HIV-1/physiology , Humans , Molecular Sequence Data , Receptors, CCR5/chemistry , Structure-Activity Relationship , Sulfates/pharmacology , Tyrosine
19.
J Bone Miner Res ; 13(8): 1300-7, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9718199

ABSTRACT

We examined the relationship between bone histomorphometric variables versus marrow cellularity, marrow adiposity (among hemopoietic cells), and fatty degeneration (areas of only fat) of bone marrow in iliac crest bone samples from 98 normal black (n = 53) and white (n = 45) males and females. We found blacks to have greater marrow cellularity (p = 0.0001), less marrow adiposity (among hemopoietic cells, p = 0.0001), greater values for bone volume (p = 0.030), trabecular thickness (p = 0.002), and static bone turnover variables (osteoid volume, p = 0.001; osteoid surface, p = 0.001; osteoid thickness, p = 0.001; eroded surface, p = 0.0006) than whites. Marrow cellularity correlated positively with static bone turnover variables osteoid volume (r = 0.257, p = 0.011), osteoid surface (r = 0.265, p = 0.008), osteoid thickness (r = 0.217, p = 0.032), and eroded surface (r = 0.273, p = 0.007) when all 98 cases were analyzed together. These findings suggest that marrow cells may influence bone turnover. The extent of fatty degeneration, but not that of adipose tissue, increased with age in blacks (r = 0.476, p = 0.0003) and whites (r = 0.476, p = 0.001), as did bone loss. There was no racial difference in the extent of fatty degeneration. We conclude that the lesser extent of adiposity in blacks is a racial characteristic that is unaffected by aging, whereas fatty degeneration which may have partly occupied space vacated by bone loss, is an aging phenomenon, unrelated to race. Greater bone turnover in blacks may be expected to lead to more frequent renewal of fatigue-damaged bone, which together with sturdier bone structure may contribute to the lower fragility fracture rates in blacks.


Subject(s)
Black People , Bone Marrow Cells/cytology , Ilium/anatomy & histology , Ilium/ultrastructure , White People , Adult , Age Factors , Bone Marrow Cells/metabolism , Bone Remodeling , Female , Humans , Male , Middle Aged , Sex Factors
20.
Bone ; 22(3): 259-65, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9514218

ABSTRACT

African teenagers with slipped capital femoral epiphysis (SCFE) not infrequently also have genu valgum (knock-knee). Because we had previously demonstrated metabolic bone disease attributable to dietary calcium deficiency in black teenagers with genu valgum, we examined 29 black teenagers (15 male, 14 female) with SCFE for metabolic bone disease. Each patient had an iliac crest bone biopsy taken (after double tetracycline labeling) for routine histomorphometry, and blood and urine samples for bone biochemistry. Spinal bone mineral density was measured in 13 patients. Compared to reported data, we found our patients to be sexually more immature, older, at least as obese, and to have more severe and more frequently bilateral hip disease. Eighty percent of the children took dairy products only once or twice a week or less frequently, and 37.9% had genu valgum. Compared with race- and age-matched South Africans, bone biopsies in our patients showed lower bone volume (BV/TV, p = 0.0003), wall thickness (p = 0.0002), and trabecular thickness (Tb.Th, p = 0.0002), and a tendency to greater trabecular spacing (Tb.Sp, p = 0.053). Lower osteoid volume (OV/BV, p = 0.0001), osteoid surface (OS/BS, p = 0.0001), osteoid thickness (O.Th, p = 0.0002), double labeled surface (dLS/BS, p = 0.029), and bone formation rate (BFR/BS, p = 0.037) suggested poorer bone forming capacity in our patients. No evidence of hyperparathyroid bone disease or osteomalacia was found. BV/TV was below the reference range (14.2%) in 65.5% of cases; these patients had lower values for Tb.Th (p = 0.037) and Tb.N (p = 0.0003), greater Tb.Sp (p = 0.0002), a tendency to lower adjusted apposition rate (Aj.AR, p = 0.057), and had had less frequent intake of dairy products than those with normal BV/TV (p = 0.024). Furthermore, months since menarche correlated with histomorphometric variables BV/TV (r = 0.667, p = 0.009), Tb.Th (r = 0.745, p = 0.002), Tb.Sp (r = -0.549, p = 0.042), O.Th (r = 0.784, p = 0.0009), and Aj.AR (r = 0.549, p = 0.042). The correlation between Tb.Th and spinal bone mineral content (r = 0.656, p = 0.015) suggests that the reduced trabecular thickness reflected a generalized bone condition. A greater than normal proportion of patients had spinal bone mineral density values below -1 standard deviation (SD) of the mean (osteopenia) (p = 0.001). Patients tested for parathyroid hormone and 25-hydroxyvitamin D levels were found to have normal values. Parathyroid hormone correlated with Aj.AR (r = 0.661, p = 0.038) and serum phosphorus (r = -0.764, p = 0.010). We conclude that sexual immaturity and possibly past dietary calcium deficiency contributed to osteopenia, and that this, together with obesity, led to the development of more severe and more frequently bilateral SCFE in our patients than in reported series of black and white children.


Subject(s)
Black People , Bone Diseases, Metabolic/complications , Cartilage Diseases/complications , Epiphyses, Slipped/complications , Femur Head/pathology , Adolescent , Biopsy , Body Weights and Measures , Bone Density , Bone Diseases, Metabolic/ethnology , Bone Diseases, Metabolic/pathology , Cartilage Diseases/ethnology , Cartilage Diseases/pathology , Child , Epiphyses, Slipped/ethnology , Epiphyses, Slipped/pathology , Female , Humans , Ilium/diagnostic imaging , Ilium/pathology , Lumbar Vertebrae , Male , Puberty , Radiography , South Africa
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