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Biomedical subjects

J C Rutledge

Publications and source records attributed to J C Rutledge.

At least 19 recordsLinked to original sources
PubMed2006

Multinutrient supplement containing ephedra and caffeine causes weight loss and improves metabolic risk factors in obese women: a randomized controlled trial.

OBJECTIVE: To determine the safety and efficacy of a dietary supplement with a low dose of ephedra and caffeine in overweight/obese premenopausal female subjects. DESIGN: A 9-month, double-blind, randomized control study compared the efficacy and safety of a dietary supplement with ephedra and caffeine to a control supplement. SUBJECTS: Sixty-one healthy, premenopausal women with body mass index (BMI) from 27 to 39 kg/m2 were randomly assigned and received a dietary supplement (40 mg/day ephedra alkaloids, 100 mg/day caffeine, high potency mixture of vitamins, minerals, omega-3 fatty acids) or a control supplement for 9 months. MEASUREMENTS EFFICACY: changes in body weight, body composition, lipids, insulin, leptin, adiponectin, ghrelin, and self-reports of physical activity, diet and quality of life indices. SAFETY: blood pressure, heart rate, electrocardiograms, urinalysis, blood histology, serum chemistry measures and self-reported symptoms. RESULTS: Forty-one women completed the study. The treatment group lost significantly more body weight (-7.18 kg) and body fat (-5.33 kg) than the control group (-2.25 and -0.99 kg, respectively), and showed significant declines in heart rate, serum cholesterol, triglycerides, cholesterol to high-density lipoprotein ratio, glucose, fasting insulin, and leptin. Blood pressure, electrocardiograms, other clinical chemistry measures, blood histology, urinalysis, and self-reported physical activity were similar in the groups. Minor symptoms included dry mouth, insomnia, nervousness and palpitations. The treatment group reported more energy and decreased appetite compared to controls and scored higher on a quality of life domain assessing vitality. CONCLUSION: A dietary supplement containing a low potency ephedra/caffeine mixture appeared safe and effective in causing loss of weight and body fat, and improving several metabolic parameters, including insulin sensitivity and lipid profiles when tested under physician supervision. Such supplements could be a useful tool to assist with weight loss.

Adult↗
PubMed2005

Raman spectroscopic analysis of biochemical changes in individual triglyceride-rich lipoproteins in the pre- and postprandial state.

Individual triglyceride-rich lipoprotein (TGRL) particles derived from human volunteers are nondestructively analyzed by laser tweezers Raman microspectroscopy, and information on their composition and distribution is obtained. The Raman signature of single optically trapped very low-density lipoproteins (VLDL), a subclass of TGRL, which play an important role in cardiovascular disease, exhibits distinct peaks associated with molecular vibrations of fatty acids, proteins, lipids, and structural rearrangements of lipids. Our analysis of pre- and postprandial VLDL exhibits the signature of biochemical changes in individual lipoprotein particles following the consumption of meals. Interaction of VLDL with endothelium leads to the breakdown of complex triacylglycerols and the formation of a highly ordered core of free saturated fatty acids in the particle. A particle distribution analysis reveals trends in the degree to which this process has occurred in particles at different times during the postprandial period. Differences in particle distributions based on the different ratios of polyunsaturated to saturated fats in the consumed meals are also easily discerned. Individual lipoprotein particles hydrolyzed in vitro through addition of lipoprotein lipase (LpL) exhibit strikingly similar changes in their Raman spectra. These results demonstrate the feasibility of monitoring the dynamics of lipid metabolism of individual TGRL particles as they interact with LpL in the endothelial cell wall using Raman spectroscopy.

Adult↗
PubMed2002

Exponential processes in human auditory excitation and adaptation.

Peripheral auditory adaptation has been studied extensively in animal models, and multiple exponential components have been identified. This study explores the feasibility of estimating these component processes for human listeners with a peripheral model of adaptation. The processes were estimated from off-frequency masked detection data that probed temporal masking responses to a gated narrowband masker. The resulting response patterns reflected step-like onset and offset features with characteristically little evidence of confounding backward and forward masking. The model was implemented with linear combinations of exponential functions to represent the unadapted excitation response to gating the masker on and then off and the opposing effects of adaptation in each instance. The onset and offset of the temporal masking response were assumed to be approximately inverse operations and were modeled independently in this scheme. The unadapted excitation response at masker onset and the reversed excitation response at masker offset were each represented in the model by a single exponential function. The adaptation processes were modeled by three independent exponential functions, which were reversed at masker offset. Each adaptation component was subtractive and partially negated the unadapted excitation response to the dynamic masker. This scheme allowed for quantification of the response amplitude, action latency, and time constant for the unadapted excitation component and for each adaptation component. The results reveal that (1) the amplitudes of the unadapted excitation and reversed excitation components grow nonlinearly with masker level and mirror the 'compressive' input-output velocity response of the basilar membrane; (2) the time constants for the unadapted excitation and reversed excitation components are related inversely to masker intensity, which is compatible with neural synchrony increasing at masker onset (or offset) with increasing masker strength; (3) the composite strength of adaptation levels off at high masker levels; this 'saturation' response is consistent with a diminished contribution from peripheral neural adaptation processes at high sound levels; and (4) the response dynamics for two of the adaptation components correspond generally to those for the 'very rapid'/'rapid' processes and 'short-term' processes described in animal studies of peripheral neural adaptation. The action latency of a third adaptation component suggests the role of a second-order peripheral or central process. This modeling exercise (1) indicates that multiple adaptation processes, whatever their origins, contribute substantively to the form of the temporal masking response and (2) supports a sum-of-exponentials scheme for estimating properties of the component processes.

Adaptation, Physiological↗
PubMed2001

Chronic estradiol treatment attenuates stiffening, glycoxidation, and permeability in rat carotid arteries.

Aging-related changes in vascular stiffening and permeability are associated with cardiovascular disease. We examined the interaction of estradiol on the aging process in vascular tissue from rats by assessing the changes in endothelial layer permeability, arterial compliance, and glycoxidative damage levels. We isolated carotid arteries from ovariectomized (OVX) rats that underwent 1 yr of estrogen treatment with subcutaneous pellets and a subsequent 1 mo of cessation of treatment. Endothelial layer permeability and arterial compliance were determined using quantitative fluorescence microscopy. Endothelial layer permeability was reduced with estradiol treatment (estrogen groups, 2.58 +/- 0.21 ng dextran x min(-1) x cm(-2) vs. nonestrogen groups, 4.01 +/- 0.30 ng dextran x min(-1) x cm(-2); P < 0.05). Additionally, arteries from animals treated with estradiol had an increased compliance index (estrogen groups, 82.9 +/- 3.8 mm2. Torr vs. nonestrogen groups, 69.3 +/- 3.2 mm2. Torr; P < 0.05). Estradiol treatment also reduced levels of pentosidine, which is a specific marker of glycoxidative damage (estrogen groups, 0.11 +/- 0.03 pmol pentosidine/nmol collagen vs. nonestrogen groups, 0.20 +/- 0.03 pmol pentosidine/nmol collagen; P < 0.05). These results indicate that estradiol has multiple chronic vasculoprotective effects on the artery wall to maintain normal vascular wall function.

Animals↗
PubMed2000

Depressive symptoms and risks of coronary heart disease and mortality in elderly Americans. Cardiovascular Health Study Collaborative Research Group.

BACKGROUND: Several epidemiological studies have associated depressive symptoms with cardiovascular disease. We investigated whether depressive symptoms constituted a risk for coronary heart disease (CHD) and total mortality among an apparently healthy elderly cohort. METHODS AND RESULTS: In a prospective cohort of 5888 elderly Americans (>/=65 years) who were enrolled in the Cardiovascular Health Study, 4493 participants who were free of cardiovascular disease at baseline provided annual information on their depressive status, which was assessed using the Depression Scale of the Center for Epidemiological Studies. These 4493 subjects were followed for 6 years for the development of CHD and mortality. The cumulative mean depression score was assessed for each participant up to the time of event (maximum 6-year follow-up). Using time-dependent, proportional-hazards models, the unadjusted hazard ratio associated with every 5-unit increase in mean depression score for the development of CHD was 1.15 (P:=0.006); the ratio for all-cause mortality was 1.29 (P:<0.0001). In multivariate analyses adjusted for age, race, sex, education, diabetes, hypertension, cigarette smoking, total cholesterol, triglyceride level, congestive heart failure, and physical inactivity, the hazard ratio for CHD was 1.15 (P:=0.006) and that for all-cause mortality was 1.16 (P:=0.006). Among participants with the highest cumulative mean depression scores, the risk of CHD increased by 40% and risk of death by 60% compared with those who had the lowest mean scores. CONCLUSIONS: Among elderly Americans, depressive symptoms constitute an independent risk factor for the development of CHD and total mortality.

Aged↗
PubMed2000

Direct visualization of lipid deposition and reverse lipid transport in a perfused artery : roles of VLDL and HDL.

The major goal of this study was to determine the interactions of VLDL surface and core lipids with the artery wall. We first demonstrated in vitro that surface lipid in VLDL could be traced using the phospholipid-like fluorescent probe 1,1'-dioctadecyl-3,3, 3',3'-tetramethyl-indocarbocyanine (DiI). The core of VLDL particles was traced by fluorescently labeling apolipoprotein B with TRITC. The labeled VLDLs were perfused through rat carotid arteries, and accumulation of the fluorescently labeled VLDL components in the arterial walls was determined by quantitative fluorescence microscopy. Addition of lipoprotein lipase increased the accumulation of both DiI and TRITC by >2.3-fold. Histological examination showed that DiI and TRITC were primarily localized to the endothelial layer; however, DiI also accumulated as small "lakes" deeper in the artery, in a subendothelial position. Addition of HDL to the perfusion decreased the accumulation of surface lipid and apolipoprotein B-containing particles and eliminated the DiI lakes. Moreover, the increase in endothelial layer permeability associated with lipolysis was attenuated 21% by HDL. If VLDL surface lipid first was allowed to accumulate in the arterial wall, its subsequent rate of loss was more than twice as fast if HDL was included in the perfusate. These studies directly demonstrate atherogenic effects of VLDL lipolysis and their inhibition by HDL.

Animals↗
PubMed2000

Smoking and cardiovascular disease.

Mainstream and ETS exposure are strong risk factors for cardiovascular disease in men and women. The relationships between smoking and cardiovascular disease result from multiple mechanisms that interact to contribute to atherosclerosis, vascular injury, thrombosis, and vascular dysfunction. We are only now beginning to understand how smoking contributes to the genesis and progression of cardiovascular disease. Because of the complexity of the interactions between nicotine and the components of MSS, ETS, and sidestream smoke with the vasculature, it will take a great deal of time and effort to fully unravel the mechanisms by which smoking contributes to cardiovascular disease. In addition, cardiovascular risk in female smokers is complicated by hormonal variables that may contribute to greater relative risk. It is important that health care providers, educators, and policy makers recognize the changing patterns of smoking and the impact of smoking on cardiovascular disease, and continue campaigns aimed at enhancing smoking cessation in the general population and in teens. Rigorous research is needed on the changing cultural, psychosocial, and environmental factors that influence tobacco use to improve our understanding of racial/ethnic smoking patterns, and identify strategic tobacco control opportunities. The capacity of tobacco control efforts to keep pace with patterns of tobacco use and cessation depends on timely recognition of emerging prevalence and cessation patterns and the resulting development of appropriate community-based programs to address the factors involved. Smoking trends today will determine how heavy the health burden of cardiovascular disease and others will be among communities tomorrow. Programs that aim at early intervention and reflect cultural diversity will be the cornerstone in the battle against tobacco use. Continued interest in research, educational, and prevention efforts are needed to help curb the risk of cardiovascular disease from smoking in men and women.

Animals↗
PubMed2000

17beta-estradiol acts separately on the LDL particle and artery wall to reduce LDL accumulation.

Estrogen replacement therapy has been shown to attenuate atherogenesis, although the mechanisms for this effect are incompletely defined. Previously, we showed that 17-beta estradiol (estradiol) attenuated oxidant stress-induced increases in vascular low density lipoprotein (LDL) accumulation. It was unclear whether estradiol's effect was imparted on the lipoprotein particle or the artery wall. To examine this, we chronically treated rats with the following sex hormones: low estradiol, high estradiol, progesterone, low estradiol + progesterone, placebo, or control. Carotid arteries (n = 8/group) were isolated and perfused with fluorescently labeled LDL. Rates of LDL accumulation were measured before and after treatment with 10 ng/ml tumor necrosis factor-alpha (TNF) using quantitative fluorescence microscopy. We observed a 50% decrease in basal LDL accumulation rates (P < 0.01) and a 25% decrease in endothelial layer permeability (P < 0.01) in arteries from estradiol-treated animals. There was no effect of hormone replacement on rate of TNF-induced LDL accumulation (P = 0.451), while incubation of LDL with 65 pg/ml estradiol attenuated the TNF effect (P < 0.01). These experiments suggest two independent mechanisms of anti-atherogenic protection by estradiol: 1) decreased endothelial layer permeability; and 2) incorporation of estradiol into the LDL particle and prevention of LDL binding to the artery wall.

Animals↗
PubMed1999

The clinical impact of increased sensitivity PT and APTT coagulation assays.

To determine how more-sensitive prothrombin time (PT) and activated partial thromboplastin time (aPTT) reagents affected the number and distribution of abnormal test results and whether the increased sensitivity for deficiencies resulted in improved diagnosis of clinically significant coagulopathies, we retrospectively compared preoperative coagulation screening data for 140 children undergoing open heart surgery after the reagent change with a similar group of 135 before the change. The more sensitive reagents resulted in a higher rate of abnormal values, but no increase in the identification of clinically significant hemostatic abnormalities. Of 67 patients with abnormal aPTTs in the group screened with more sensitive reagents, 63 had no further workup. No patients in either group were diagnosed subsequently with a coagulopathy because of unexpected bleeding. An abnormal test result did not predict the need for perioperative blood products. We hypothesize that the high frequency of abnormal aPTTs led to physician "desensitization" about the merit of coagulation screening. Therefore, we question the usefulness of preoperative coagulation screening of the pediatric cardiac surgery patient, particularly since lasting changes in physician perception regarding the clinical significance of abnormal values may lead to missed diagnoses in other settings.

Adolescent↗
PubMed1999

17 beta-estradiol reduces glycoxidative damage in the artery wall.

Glycoxidative damage in the vasculature has been linked to atherosclerotic cardiovascular disease. Estrogens protect against the development and progression of atherosclerosis. Because estrogens are potent antioxidants that also effect glucose metabolism, part of their protection against atherosclerosis could be through attenuation of glycoxidative damage in the vascular wall. In this study, we tested the hypothesis that chronic estradiol administration is associated with decreased levels of glycoxidative damage in arterial walls. We harvested and examined iliac arteries from ovariectomized, 8-month-old rats that had been implanted for 6 months with 1 of the following subcutaneous hormone pellets: low estradiol (2.5 mg estradiol), high estradiol (25 mg estradiol), P4 (200 mg progesterone), low estradiol and P4, placebo (no hormone), or control (no implant). Using pentosidine as a biomarker of glycoxidative damage, we found that all vessels from rats receiving estradiol (low estradiol, high estradiol, and low estradiol+P4) exhibited a 50% reduction in glycoxidative damage compared with P4, placebo, and control vessels (P<0.05). Consistent with this finding, we observed that estradiol-treated rats had a 30% decrease in tissue levels of hydroperoxides, a marker of oxidative stress. Finally, estradiol-treated rats had a small, but significant, decrease in plasma glucose levels (P<0.01). In summary, we report the novel finding that chronic estrogen administration is associated with significant decreases in glycoxidative damage and oxidative stress in the arterial wall. It seems likely that these actions may constitute a mechanism by which estrogen attenuates the progression of atherosclerosis.

Animals↗
PubMed1999

Modified LDL-mediated increases in endothelial layer permeability are attenuated with 17 beta-estradiol.

-Current research suggests that estrogen may have primary effects on the artery wall. To investigate the mechanisms of female sex hormone actions in the artery wall, we used an isolated, perfused, rat carotid artery model to examine the effects of estradiol on the rates of accumulation of normal (N-LDL) and minimally modified (MM-LDL) low density lipoprotein in ovariectomized rats. N-LDL, MM-LDL, and oxidized LDL (OX-LDL) were fluorescently labeled and perfused into individual arteries. The rate of LDL accumulation was measured by quantitative fluorescence microscopy before and after treatment with estradiol (1 nmol/L, 272 pg/mL). Estradiol had no effect on the rate of N-LDL accumulation (45+/-12 versus 48+/-15 ng cholesterol per cm2 per h). However, estradiol significantly decreased the rate of MM-LDL (240+/-48 versus 160+/-48 ng cholesterol per cm2 per h; P<0.05) and OX-LDL (191+/-53 versus 112+/-36 ng cholesterol per cm2 per h; P<0.05) accumulation. Further experiments showed that perfusion of unlabeled MM-LDL (100 microgram/mL) increased endothelial layer permeability when the rate of accumulation of a water-soluble, fluorescently labeled, reference molecule (64 000-molecular weight dextran) was determined before and after perfusion of MM-LDL (319+/-96 versus 510+/-191 ng per cm2 per h, n=6 arteries; P<0.05). Estradiol prevented the expected increase in the rate of dextran accumulation when perfused with MM-LDL (control, 415+/-49 ng per cm2 per h and MM-LDL+estradiol, 415+/-160 ng per cm2 per h). Our studies show that estradiol prevents compromise of the endothelial barrier mediated by MM-LDL and attenuates accumulation of MM-LDL in the artery wall.

Animals↗
PubMed1999

17beta-estradiol reduces tumor necrosis factor-alpha-mediated LDL accumulation in the artery wall.

Estrogens have direct effects on the vascular wall that may prevent the development of atherosclerosis. In particular, estrogens, such as 17beta-estradiol (estradiol), are known to have potent antioxidant activity. Tumor necrosis factor-alpha (TNF) is found in human atheroma and produces oxygen-derived free radicals. These oxygen-derived free radicals may modify low density lipoproteins (LDL) and increase LDL binding in the artery wall. We asked: 1) does TNF increase LDL accumulation in the artery wall and 2) can the TNF-mediated increase in LDL accumulation be prevented by the antioxidant activity of estradiol? Carotid arteries from ovariectomized 3-month-old rats were removed and perfused with fluorescently labeled LDL and arterial LDL flux was measured using quantitative fluorescence microscopy. In six arteries, addition of TNF (10 ng/ml) to the perfusate resulted in a 2.3-fold increase in the rate of LDL accumulation (1.50 +/- 0.37 ng/min per cm2 vs. 3.38 +/- 0.48 ng/min per cm2; P < 0.01). Estradiol (65 pg/ml) and alpha-tocopherol (6 mg/L) both attenuated TNF-mediated LDL accumulation (P < 0.05), indicating that TNF may exert its effects on LDL accumulation through cellular production of oxygen-derived free radicals. These results support an antioxidant role for estradiol in the protection against LDL accumulation in the artery wall and subsequent progression of atherosclerosis.

Animals↗
PubMed1998

Parvovirus B19-induced anemia as the presenting manifestation of X-linked hyper-IgM syndrome.

Parvovirus B19 (B19) can cause chronic anemia due to persistent infection in immunocompromised hosts who cannot produce neutralizing antibody necessary for clearing B19. Three patients with X-linked hyper-IgM syndrome (XHIM), who were all asymptomatic until they developed B19-induced chronic anemia at the ages of 8, 14, and 17 years, respectively, were found to have mutations of the CD40L gene, including a missense mutation (T254M), a nonsense mutation resulting in a new initiation codon and loss of the intracellular domain (R11X), and a splice site mutation (nt 309+2t-->a). Antibody responses to the T cell-dependent antigen, bacteriophage phiX174, were impaired, but neutralizing antibody titers were higher than in XHIM patients with classic phenotype. All 3 patients responded to intravenous immune globulin (IVIG) treatment. Certain mutations of the CD40L gene result in a mild XHIM phenotype that may become apparent following B19 infection in patients not on IVIG therapy and therefore not protected from B19 infection.

Adolescent↗
PubMed1998

Reduced oxidative susceptibility of LDL from patients participating in an intensive atherosclerosis treatment program.

The goal of this investigation was to determine whether participation in an atherosclerosis treatment program would reduce the oxidative susceptibility of LDL from patients with coronary artery disease. The treatment program included intensive exercise therapy, stress management, and consumption of a diet containing 10% fat. The size and antioxidant and lipid contents of LDL particles from 25 patients were analyzed at baseline and after 3 mo of therapy. The susceptibility of LDL to copper-mediated oxidation was measured by a conjugated diene assay and headspace gas chromatography (HSGC). Atherosclerosis treatment significantly reduced plasma total cholesterol and apolipoprotein B concentrations and the molar ratio of LDL cholesterol ester to apolipoprotein B (P < 0.01). The LDL content of alpha-tocopherol and beta-carotene was increased (27% and 17%, respectively, P < 0.04) and the molar ratio of LDL cholesterol ester the sum of LDL alpha-tocopherol and LDL beta-carotene decreased from 159 at baseline to 122 at 3 mo (P < 0.01). The lag phase of LDL conjugated diene formation increased 24%, whereas the maximum rate of oxidation slowed 29% (P < 0.01). As assessed by HSGC, copper-catalyzed formation of volatile lipid oxidation products was reduced 15% (P < 0.007); the reduction in volatiles was correlated with an increase in the alpha-tocopherol content of LDL (r=-0.48, P < 0.01). The principal determinants of reduced LDL oxidative susceptibility were the particle contents of alpha-tocopherol and beta-carotene. To our knowledge, this is the first report to document a reduction in LDL oxidation in coronary artery disease patients undergoing atherosclerosis-reversal therapy.

Aged↗
PubMed1998

Brachydactyly type A1 with abnormal menisci and scoliosis in three generations.

We report a three-generation family in which four members had brachydactyly type A1, degenerative arthritis of the knee as a complication of abnormal menisci, and variable scoliosis. Nine of the 15 individuals in the two generations preceding the proband had brachydactyly. Three of these nine had degenerative arthritis of the knee including the proband's father who had meniscal degeneration with tears. One other had radiologically confirmed discoid menisci. Of those with brachydactyly, five also had scoliosis. Although autosomal dominant inheritance of brachydactyly A1 and discoid menisci have been reported separately, cosegregation of these features in one family has not previously been described and seems to comprise a unique autosomal dominant condition. The combination of brachydactyly, meniscal abnormalities including discoid meniscus, and scoliosis suggests that this disorder represents a new osteochondrodysplasia syndrome.

Child↗
PubMed1997

Developmental toxicity induced during early stages of mammalian embryogenesis.

Both a conceptual and a practical borderland between teratology and mutagenesis is early embryogenesis, the period between fertilization and gastrulation. Radiation and a variety of chemicals adversely affect the early conceptus leading to in utero mortality and malformations. The post-fertilization period of susceptibility differs from exposures of gametes, the later producing excessive pre- and peri-implantational death and low rates of fetal anomalies predominated by growth retardation. In contrast mutagen exposure of the zygote induces peri-implantational death, pan-gestational death and fetal anomalies predominated by hydrops, abdominal wall defects, and eye aberrations. The mechanism for this pathology remains unclear. These same agents produce a broader range of phenotypic anomalies during the remainder of pre-gastrulation development with anomalies overlapping those induced during organogenesis. Retinoic acid and 5-azacytidine administered prior to gastrulation produce novel malformation syndromes indicative of gene expression modification. The rates and types of defects from mutagen treatment of both gametes and the early conceptus contrast with those resulting from embryonic treatment during organogenesis, and the mechanisms are likely to differ. The pre-gastrulation period has not been explored to the extent reported during gametogenesis or organogenesis. Pre-gastrulation teratology is a new area of investigation with relevance both to reproductive toxicology and to mammalian developmental biology.

Abnormalities, Drug-Induced↗
PubMed1997

The ultrastructure of skin from a patient with mucopolysaccharidosis IIID.

Mucopolysaccharidosis IIID (MPS-IIID) is the rarest of the MPS-III syndromes. It is caused by deficient activity of lysosomal N-acetylglucosamine-6-sulfatase (G6S). To date, the clinical and biochemical features of seven patients with MPS-IIID have been reported, but no biopsy or autopsy findings have been described. The purpose of this report is to define the ultrastructure of affected cells seen in a skin biopsy from a 14-year-old boy. The child presented with progressive mental deterioration, hyperactivity and mild to moderate dysmorphism. The diagnosis of a mucopolysaccharidosis was suggested, but the initial urine analyses were negative for elevated mucopolysaccharides, and only the third analysis showed abnormal excretion of heparan sulfate. Because of the diagnostic difficulties posed by this case, a skin biopsy was performed for morphological and biochemical studies. Numerous vacuoles were noted in Schwann cells, fibroblasts, smooth muscle cells, eccrine gland and ductal epithelium in resin-embedded sections stained with toluidine blue. Ultrastructurally, many lysosomes were distended with abundant, fibrillar material. Occasionally, lamellated membranous structures were present within the same lysosomes. These findings are consistent with those seen in other forms of MPS, in which the lysosomal storage occurs predominantly, but not exclusively, in mesenchymal cells. Furthermore, deficient activity of G6S was confirmed in cultured skin fibroblasts. This study demonstrates that electron microscopy of skin biopsies is a useful method for identification of patients with clinical features of MPS-IIID whether or not heparan sulfaturia is present.

Adolescent↗
PubMed1997

Nitric oxide mediates LDL uptake in the artery wall in response to high concentrations of 17 beta-estradiol.

Female sex hormones are known to affect lipoprotein flux in the artery wall and atherosclerosis. However, the mechanisms of these artery wall effects are unclear. To examine the effect of 17 beta-estradiol (estradiol) on LDL uptake in the artery wall, we developed an isolated perfused rat carotid artery model from ovariectomized rats. LDL flux in the artery wall was measured by quantitative fluorescence microscopy before and after treatment with estradiol (0.001 to 10,000 nmol/L). Dose-response experiments showed no significant difference in the rate of LDL uptake when arteries were perfused with estradiol at physiological concentrations (0.001 to 1 nmol/L) compared with control perfusions. However, higher concentrations of estradiol (10 to 10,000 nmol/L) significantly increased the rate of LDL uptake in isolated arteries. Artery lumen volume significantly increased with perfusion of estradiol (1 to 100 nmol/L) but decreased after perfusions of higher concentrations of estradiol (1000 to 10,000 nmol/L). Additional studies were performed to examine mechanisms of estradiol-mediated increases in LDL uptake. The effect of estradiol (10 nmol/L) on the rate of LDL uptake was blocked by nitric oxide synthase inhibitors. However, the estrogen receptor antagonist tamoxifen did not block the effects of estradiol on the rate of LDL uptake. Our study indicates that modulation of LDL uptake in the artery wall by estradiol is concentration dependent. High concentrations of estradiol increase LDL uptake by production of endothelium-derived nitric oxide. These observations suggest that increased nitric oxide production compromises endothelial layer barrier function to increase LDL uptake in the artery wall.

Animals↗