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Biomedical subjects

M R Adams

Publications and source records attributed to M R Adams.

At least 91 records · Page 5Linked to original sources
PubMed1996

Effects of hormone replacement modalities on low density lipoprotein composition and distribution in ovariectomized cynomolgus monkeys.

This study was designed to determine the effect of several hormone replacement therapies on LDL size, density, heterogeneity, and composition in surgically postmenopausal cynomolgus monkeys fed an atherogenic diet. Groups (n = 5 each) of ovariectomized cynomolgus monkeys were untreated (control), or treated with conjugated equine estrogens, medroxyprogesterone acetate (progesterone), combined estrogen-progesterone, or tamoxifen for 9 weeks. There were no differences among treatment groups in total plasma, LDL, or HDL cholesterol or triglyceride concentrations. Plasma LDL were isolated by ultracentrifugation and size exclusion chromatography and subfractionated by density gradient centrifugation for subsequent chemical analysis. Estrogen treatment was associated with significantly smaller (measured as LDL molecular weight, 3.9 +/- 0.2 g/mu mol) and denser plasma LDL (1.034 g/ml peak density) compared with control (4.5 +/- 0.1 g/mu mol; 1.030 g/ml peak density) or progesterone-treated animals (4.6 +/- 0.2; 1.029 g/ml peak density). LDL from the estrogen group were relatively enriched in protein and triglyceride and poor in cholesteryl ester and apolipoprotein F (apoE) compared to the control group. Triglyceride enrichment with estrogen treatment occurred predominantly in the lighter, larger LDL subfractions (d = 1.015-1.025 g/ml), which were reduced in concentration (26 +/- 10 mg cholesterol/dl) compared to control (61 +/- 19 mg/dl) or progesterone treated animals (67 +/- 16 mg/dl). Combined estrogen-progesterone or tamoxifen treatment resulted in changes in LDL that followed the same trend as those observed with estrogen treatment. We conclude that short-term estrogen treatment of ovariectomized cynomolgus monkeys results in changes in plasma LDL size, density, and composition while having no apparent effect on overall plasma lipid concentrations.

Administration, Oral↗
PubMed1996

Passive smoking and impaired endothelium-dependent arterial dilatation in healthy young adults.

BACKGROUND: Passive smoking has been linked to an increased risk of dying from atherosclerotic heart disease. Since endothelial dysfunction is an early feature of atherogenesis and occurs in young adults who actively smoke cigarettes, we hypothesized that passive smoking might also be associated with endothelial damage in healthy young-adult nonsmokers. METHODS: We studied 78 healthy subjects (39 men and 39 women) 15 to 30 years of age (mean +/- SD, 22 +/- 4): 26 control subjects who had never smoked or had regular exposure to environmental tobacco smoke, 26 who had never smoked but had been exposed to environmental tobacco smoke for at least one hour daily for three or more years, and 26 active smokers. Using ultrasonography, we measured the brachial-artery diameter under base-line conditions, during reactive hyperemia (with flow increase causing endothelium-dependent dilatation), and after sublingual administration of nitroglycerin (an endothelium-independent dilator). RESULTS: Flow-mediated dilatation was observed in all control subjects (8.2 +/- 3.1 percent; range, 2.1 to 16.7) but was significantly impaired in the passive smokers (3.1 +/- 2.7 percent; range, 0 to 9; P < 0.001 for the comparison with the controls) and in the active smokers (4.4 +/- 3.1 percent; range, 0 to 10; P < 0.001 for the comparison with the controls; P = 0.48 for the comparison with the passive smokers). In the passive smokers, there was an inverse relation between the intensity of exposure to tobacco smoke and flow-mediated dilatation (r = -0.67, P < 0.001). In contrast, dilatation induced by nitroglycerin was similar in all groups. CONCLUSIONS: Passive smoking is associated with dose-related impairment of endothelium-dependent dilatation in healthy young adults, suggesting early arterial damage.

Adolescent↗
PubMed1996

Hormone replacement therapy is associated with improved arterial physiology in healthy post-menopausal women.

OBJECTIVE: Oestrogen replacement therapy is associated with a marked reduction in coronary event rates in post-menopausal women. As older age is associated with progressive arterial endothelial damage, a key event in atherosclerosis, we assessed whether hormone replacement therapy (HRT) with oestrogen alone, or oestrogen and progesterone combined, is associated with improved endothelial function in healthy women after the menopause. DESIGN: Using high resolution external vascular ultrasound, brachial artery diameter was measured at rest and in response to reactive hyperaemia, with increased flow causing endothelium-dependent dilatation (flow-mediated dilatation). PATIENTS: We investigated 135 healthy women; 40 were pre-menopausal (mean +/- SD age/26 +/- 6 years, group 1), 40 were post-menopausal and had never taken HRT (aged 58 +/- 3 years; group 2) and 55 were age-matched post-menopausal women who had taken HRT for > or = 2 years, from within 2 years of the menopause (aged 57 +/- 4 years; group 3). In group 3, 40 women were on combined oestrogen and progesterone and 15 on oestrogen-only HRT. RESULTS: In group 2, flow-mediated dilatation was significantly reduced compared with group 1 (4.4 +/- 3.4 vs 9.6 +/- 3.6%, P < 0.001), consistent with a decline in arterial endothelial function after the menopause. In group 3, however, flow-mediated dilatation was significantly better than group 2 (6.2 +/- 3.3 vs 4.4 +/- 3.4%, P = 0.01), suggesting a protective effect of HRT. Flow-mediated dilatation was similar in women taking oestrogen alone and in those on combined HRT (5.5 +/- 2.8 vs 6.5 +/- 3.4%, P = 0.40). CONCLUSIONS: Long-term HRT is associated with improved arterial endothelial function in healthy post-menopausal women. This benefit was observed in both the combined hormone replacement and unopposed oestrogen therapy groups. This may explain some of the apparent cardioprotective effect of HRT after the menopause.

Adolescent↗
PubMed1996

Quantitative structure activity relationship for the effect of benzoic acids, cinnamic acids and benzaldehydes on Listeria monocytogenes.

The inhibition of a cocktail of 18 strains of Listeria monocytogenes by 24 mono-, di- and tri-substituted benzoic and cinnamic acids and 16 benzaldehydes was evaluated using the concentration (C) required to give a 50% growth inhibition under anaerobic conditions at 35 degree C and pH 6.2 as a measure of biological activity (BAV). Using the method of least squares, multiple regression equations were obtained which described the contribution of some physiochemical and other structural properties of the compounds to their biological activity. The equation that best described the activity of benzoic and cinnamic acids was [formula: see text] where K is a lipophilicity parameter determined by RP-HPLC and the effect of ionization is represented by pKa. Benzaldehydes behaved differently, their activity being best described by the equation. [formula: see text] where the activity is controlled by a steric parameter, the van der Waals volume (Vw), and an electronic-steric parameter for ortho substituents. Absence of a lipophilicity parameter indicates that partitioning into the cell membrane might not be required for antimicrobial activity. The models were tested in several food systems which showed that in food with a high protein or lipid content antilisterial activity was much lower than predicted, making the models unacceptable in such circumstances.

Benzaldehydes↗
PubMed1996

Involvement of the cell envelope of Listeria monocytogenes in the acquisition of nisin resistance.

The involvement of the cell wall in the acquisition of nisin resistance by Listeria monocytogenes F6861 and its nisin-resistant mutant was investigated. Results indicated that without a cell wall, the acquired nisin resistance of the mutant was lost. Cell surface hydrophobicity was shown to correlate with nisin sensitivity; the wild type strain being more hydrophobic than its mutant. The possible role of S-layer proteins in nisin resistance was investigated. Examination of strains by freeze-etching and atomic force microscopy did not demonstrate the presence of S-layers in either strain while SDS-PAGE following S-layer extraction procedures revealed no major protein bands. Chloramphenicol did not adversely affect the frequency of isolation of nisin-resistant mutants, indicating that de novo protein synthesis was not involved. The involvement of other cell surface components, teichoic and lipoteichoic acids, was also examined. In contrast with other reports, comparison of the total phospholipid content of the mutant with its parental strain showed no significant difference (P > 0.05).

Alkanes↗
PubMed1996

The magnetic immuno-polymerase chain reaction assay for the detection of Campylobacter in milk and poultry.

A rapid and sensitive technique, based on the magnetic immuno-polymerase chain reaction assay (MIPA), was developed for the detection of Campylobacter jejuni in milk and chicken products. Target bacteria are captured from the food sample by magnetic particles coated with a specific antibody and the bound bacteria then lysed and subjected to PCR. The MIPA could detect 420 cfu g-1 of chicken after 18 h, 42 cfu g-1 after 24 h, and 4.2 cfu g-1 after 36 h enrichment. For artificially contaminated milk 63 cfu ml-1 could be detected after 18 and 24 h and 6.3 cfu ml-1 after 36 h enrichment.

Animals↗
PubMed1996

Time course of cellular proliferation, intimal hyperplasia, and remodeling following angioplasty in monkeys with established atherosclerosis. A nonhuman primate model of restenosis.

Animal models of arterial injury have failed to predict effective therapy to prevent restenosis in humans. While this may relate to species differences in the control of smooth muscle cell growth, many studies have used nonatherosclerotic animals, thereby failing to consider the importance of atherosclerosis in the response to injury. In an attempt to model human restenosis more accurately, we characterized the response to angioplasty in atherosclerotic monkeys. Twenty-one cynomolgus monkeys were fed an atherogenic diet for 36 months (plasma cholesterol, 12 +/- 1 mmol/L [470 +/- 23 mg/dL]). Angioplasty was then performed in the left iliac artery. After 4, 7, 14, or 28 days, bromodeoxyuridine was given to label proliferating cells, and iliac arteries were fixed in situ at physiological pressure (5 or 6 animals at each time point). Comparisons were made between injured and uninjured iliac arteries within each animal. Angioplasty often fractured the intimal plaque and media, transiently increasing lumen caliber (4 days: lumen area, 232.5 +/- 80.3% of control) and artery size as reflected by external elastic lamina area (EEL). EEL and lumen caliber returned to baseline by 7 days. Proliferation was increased throughout the artery wall at 4 and 7 days and later declined to control rates (4 days, injured versus uninjured: adventitia, 45.0 +/- 6.2% versus 16.3 +/- 7.2%; media, 8.6 +/- 2.6% versus 0.6 +/- 0.1%; intima, 16.0 +/- 5.6% versus 7.8 +/- 3.1%). The intima thickened markedly from 14 to 28 days, but an increase in EEL generally prevented further loss of the short-term gain in lumen caliber (28 days, percent of control: intimal area, 342.8 +/- 88.9%; EEL area, 150.2 +/- 28.9%; lumen area, 119.3 +/- 21.3%). The response to angioplasty in atherosclerotic monkeys appears to closely resemble that in humans. Plaque fracture, delayed recoil, intimal hyperplasia, and remodeling may each be important in determining late lumen caliber. This primate model should prove valuable in defining cellular and biochemical mediators of human restenosis.

Angioplasty↗
PubMed1996

Esterified estrogens with and without methyltestosterone decrease arterial LDL metabolism in cynomolgus monkeys.

Although both epidemiological and experimental evidence suggests that estrogen replacement therapy reduces the risk of coronary heart disease, the mechanisms for this beneficial effect are largely unknown. Furthermore, the addition of progestins or androgens to estrogen replacement therapy is of concern. The objective of this study was to examine the effects of esterified estrogens alone or in combination with an androgen on arterial LDL metabolism and early atherogenesis in ovariectomized female cynomolgus monkeys. Arterial LDL metabolism was assessed by using dual-labeled LDL that was injected 24 hours before necropsy. Arterial LDL degradation was reduced by 64% to 84% and cholesteryl ester content was decreased by approximately 50% in the thoracic aorta in both treatment groups compared with controls. In addition, aortic lipid peroxidation products, as assessed by thiobarbituric acid reaction, were significantly lower in animals treated with esterified estrogens, with a similar trend for combined estrogen-androgen treatment. Both treatments also reduced plasma concentrations of apoB-containing lipoproteins, reduced LDL particle size, and increased total-body LDL catabolism. The combination of decreased arterial LDL metabolism, decreased arterial lipid peroxidation, and improved plasma lipoprotein metabolism may explain some of the protective effects of estrogens on coronary heart disease and indicate that beneficial actions extend to a combination of estrogen and androgen.

Animals↗
PubMed1996

Effects of hormonal therapies and dietary soy phytoestrogens on vaginal cytology in surgically postmenopausal macaques.

OBJECTIVE: To evaluate the effects of conjugated equine estrogens, medroxyprogesterone acetate (MPA), conjugated equine estrogens combined with MPA, tamoxifen, and soybean estrogens on vaginal cytology in surgically postmenopausal cynomolgus macaques (Macaca fascicularis). DESIGN: Randomized long-term experimental trial. SETTING: Cytologic samples were taken from animals in two long-term randomized studies of the effects of hormonal and dietary effects on atherosclerosis. PATIENTS: Surgically postmenopausal cynomolgus macaques. INTERVENTIONS: Conjugated equine estrogens at the doses given do not exert an estrogenic effect on the with MPA, tamoxifen, and soybean estrogens were given via the diet, at doses scaled from those given to women. MAIN OUTCOME MEASURE: Vaginal cytologic maturation index. RESULTS: Conjugated equine estrogens elicited a marked maturation effect, which was antagonized partially by the addition of MPA. Tamoxifen produced a lesser estrogenic response. The cytologic pattern in animals given soybean estrogens or MPA alone did not differ from that of controls. CONCLUSION: Soybean estrogens at the doses given do not exert an estrogenic effect on the vagina of macaques. Conjugated equine estrogens are potent inducers of vaginal keratinization in this model; tamoxifen has a lesser effect. Medroxyprogesterone acetate partially antagonizes the effects of conjugated equine estrogens, and has no effect when given alone. The results support the possibility that soybean estrogens may be a "tissue-selective" estrogen with minimal effects on the reproductive tract.

Animals↗
PubMed1995

Carotid intima-media thickness is only weakly correlated with the extent and severity of coronary artery disease.

BACKGROUND: Intima-media thickness (IMT) of the common carotid artery (CCA), measured with external vascular ultrasound, has been widely used in clinical trials as a surrogate marker for coronary atherosclerosis. Despite this, the degree of correlation between carotid IMT and the extent and severity of coronary artery disease (CAD) is not known. METHODS AND RESULTS: Common carotid IMT was measured by ultrasound in 350 consecutive subjects of age 60 +/- 10 years (range, 30 to 85 years) on the day of coronary angiography. Carotid mean IMT was 0.83 +/- 0.20 mm (range, 0.43 to 1.80 mm), and maximum IMT was 1.04 +/- 0.27 mm (range, 0.49 to 2.19 mm). Coronary angiograms were analyzed by independent observers for disease severity (number of vessels with > or = 70% stenosis), extent score, and a modified Gensini score. Mean carotid IMT was weakly but significantly correlated with CAD severity (r = .26), extent (r = .23), and modified Gensini score (r = .29, P < .0001 for all correlations). Carotid IMT was not clinically useful, however, because it was not specific or sensitive enough to identify patients with or without significant CAD. Increasing age, male sex, and presence of diabetes were all associated with a significantly (P < .01) higher CAD score than the average for any level of carotid IMT, suggesting differential effects of these traditional risk factors on the coronary and common carotid arteries. CONCLUSIONS: Although carotid IMT is significantly correlated with extent and severity of CAD, the relationship is weak. This relatively poor correlation (r2 < .10) should be considered in the interpretation of clinical trials that use carotid IMT as a surrogate end point for coronary atherosclerosis.

Cardiac Catheterization↗
PubMed1995

Estrogen modulates the inducible expression of platelet-derived growth factor mRNA by monocyte/macrophages.

We examined the effects of estrogen, 12-O-tetradecanoylphorbol 13 acetate (TPA), and lipopolysaccharide (LPS) on the gene expression of platelet-derived growth factor (PDGF) by the monocyte/macrophage cell line, THP-1. THP-1 cells were exposed to TPA for 48 or 96 hours to induce differentiation. Some were treated with LPS in the last 3 hours and/or ethinyl estradiol (estrogen) (10(-9) M) in the last 20 hours. Total cellular RNA was isolated and cDNA was synthesized and then coamplified (with an internal control, beta-actin, product size 1126 bp) using polymerase chain reaction (PCR) and a set of primers for PDGF-A (product size 225 bp), PDGF-B (217 bp), or PDGF beta-receptor (PDGF-R) (228 bp). The products were separated on an agarose gel and the ratios of radioactivity incorporated into PDGF PCR products to beta-actin products were used to assess the relative changes in the levels of PDGF mRNA abundance in response to various inducers. TPA induced the expression of PDGF-A mRNA, whereas LPS had no effect. Treatment of TPA-stimulated cells with estrogen caused a 61% and 190% increase in PDGF-A mRNA (p < 0.05) at 48 and 96 hours, respectively. Addition of estrogen to cells treated with both TPA and LPS did not cause any significant change in the amounts of the transcripts. In contrast to PDGF-A mRNA, attempts to visualize and estimate PDGF-B and PDGF-R mRNA were unsuccessful. This was probably due to low levels of these transcripts in THP-1 cells. The results indicate that estrogen modulates PDGF-A gene expression by monocyte/macrophages and suggest that estrogen may influence atherogenesis at the vascular level.

Arteriosclerosis↗
PubMed1995

Capacitance measurement to assess acid-induced injury to Salmonella enteritidis PT4.

Capacitance measurement was compared with colony counting procedures for the enumeration and determination of sub-lethal injury of Salmonella enteritidis during storage under varied conditions of pH, acidulant and temperature. Capacitance monitoring was shown to offer an improved technique for the measurement of sub-lethal injury in cell populations. Higher levels of sub-lethal injury were detected by the extension of capacitance detection time than were indicated by differential colony counts on selective and non-selective media. The extension of capacitance detection time noted with sub-lethally injured cell populations was shown to be due to an extended lag phase when cells were placed in the capacitance growth medium and not the result of delayed detection of the growth of a small, uninjured sub-population. Acetic and lactic acids showed both greater lethality and greater ability to inflict sub-lethal injury than the stronger citric or hydrochloric acid. Sub-lethal injury and lethality were not simply related, as little sub-lethal injury was observed with the stronger acids even under conditions that were ultimately highly lethal. The results indicate that weak organic acids cause more reversible damage to cellular sites prior to death: an observation that has implications for choice of resuscitation procedures when examining acidified foods.

Acids↗
PubMed1995

Oral L-arginine inhibits platelet aggregation but does not enhance endothelium-dependent dilation in healthy young men.

OBJECTIVES: Our aim was to assess the effect of oral L-arginine on endothelial or platelet physiology in humans. BACKGROUND: L-Arginine is the substrate for nitric oxide synthesis, and in cholesterol-fed rabbits, oral L-arginine improves endothelium-dependent dilation, inhibits platelet aggregation and reduces atheroma. In hypercholesterolemic humans, intravenous L-arginine immediately improves endothelium-dependent dilation; however, the vascular effects of oral L-arginine in healthy humans have not previously been investigated. METHODS: In a prospective, double-blind, randomized crossover trial, 12 healthy young men 27 to 37 years old took L-arginine (7 g three times daily) or placebo for 3 days each, separated by a washout period of 7 to 14 days. RESULTS: After L-arginine, plasma levels of arginine (mean +/- SEM 303 +/- 36 vs. 128 +/- 12 mumol/liter, p = 0.01) and urea (6.7 +/- 0.5 vs. 5.2 +/- 0.2 mmol/liter, p < 0.01) were higher than levels measured after placebo, and platelet aggregation in response to adenosine diphosphate was markedly impaired (37 +/- 12% vs. 81 +/- 3%, p = 0.02). The inhibition of platelet aggregation correlated with the plasma level of L-arginine (r = 0.74, p = 0.01), and it could be completely or partially reversed by ex vivo incubation with N-monomethyl-L-arginine, a specific nitric oxide synthase inhibitor. Platelet cyclic guanosine monophosphate levels were higher after oral L-arginine than at baseline (1.91 +/- 0.46 vs. 1.38 +/- 0.40 pmol/10(9) platelets, p = 0.04). No changes were seen in fasting lipid levels, heart rate, blood pressure, endothelium-dependent dilation of the brachial artery (measured in response to reactive hyperemia, using external vascular ultrasound) (6.1 +/- 0.7% vs. 6.5 +/- 0.7%, p = NS) or in plasma levels of nitrosylated proteins (a marker of in vivo nitric oxide production) (3.5 +/- 0.5 vs. 3.3 +/- 0.4 mumol/liter, p = NS) 1 to 1.5 h after the last dose of L-arginine. CONCLUSIONS: In these healthy young adult men, oral L-arginine inhibited platelet aggregation by way of the nitric oxide pathway. However, it had no effect on systemic hemodynamic variables, plasma nitrosylated protein levels or endothelium-dependent dilation. Therefore, at certain doses, oral L-arginine may result in a relatively platelet-specific increase in nitric oxide production.

Administration, Oral↗
PubMed1995

Dominant social status and contraceptive hormone treatment inhibit atherogenesis in premenopausal monkeys.

The stress of social subordination is associated with exacerbation of coronary artery atherosclerosis in premenopausal cynomolgus monkeys, possibly as a result of the ovarian dysfunction that reliably accompanies subordinate social status. The primary objective of the current study was to determine whether treatment with an oral contraceptive (OC) provides relative protection from development of atherosclerotic plaques, especially among animals made vulnerable to atherosclerosis by social subordination. In the present study, 193 adult female monkeys (Macaca fascicularis) were placed in social groups of 5 or 6 animals each. Half of the animals were then fed an atherogenic diet to which had been added a triphasic OC, while the remainder received only the atherogenic diet. At the end of 26 months, atherosclerosis was measured in an iliac artery biopsy taken from each monkey. The results demonstrated that among untreated animals subordinate individuals developed significantly more atherosclerosis than did their dominant counterparts (P < .01); however, OC treatment inhibited atherosclerosis in subordinate animals (P < .05) and eliminated the difference between dominant and subordinate animals that was observed in the untreated condition. Subordinate social status and OC treatment were both associated with reduced plasma concentrations of HDL cholesterol (P < .01 for both), and subordinate monkeys also had elevations in LDL cholesterol plus VLDL cholesterol (P < .01). Nonetheless, the interaction between social status and OC treatment remained significant even after covariance adjustment for variation in plasma lipids. Taken together, these results suggest that social subordination worsens, whereas OC treatment inhibits, atherosclerosis, and that these effects are independent of concomitant variability in plasma lipids.

Animals↗
PubMed1995

Effects of androgens on coronary artery atherosclerosis and atherosclerosis-related impairment of vascular responsiveness.

The factors responsible for the marked gender differences in risk of coronary heart disease and atherosclerosis severity remain largely undetermined. While some clinical and experimental evidence supports a protective effect of endogenous estrogen on the initiation and progression of atherosclerosis and incidence of coronary heart disease, much of the epidemiological data do not support this conclusion. The possibility that endogenous androgens may have adverse effects on atherosclerosis progression and coronary risk has received little attention. We investigated the effects of experimentally induced hyperandrogenism in female cynomolgus monkeys with diet-induced atherosclerosis. Animals were assigned randomly to one of four treatment groups: (1) untreated controls, (2) ovariectomized (sex hormone-deficient) controls, (3) treated with androstenedione and estrone (mild hyperandrogenism), or (4) treated with testosterone (male plasma androgen pattern). At necropsy, coronary atherosclerosis was approximately twice as extensive (P < .05) in testosterone-treated animals relative to untreated controls, while treatment with androstenedione and estrone had no effect on atherosclerosis extent. Coronary plaque size was positively correlated with lumen size in intact and ovariectomized controls; however, there was no evidence of a similar relation between animals in either androgen treatment group. The atherogenic effects of testosterone were independent of variations in plasma lipoprotein and nonlipoprotein risk variables. Although chronic hyperandrogenism had adverse effects on atherosclerosis progression, it reversed (P < .03) atherosclerosis-related impairment of endothelium-dependent vasodilator responses. We conclude that an experimentally induced male plasma androgen pattern results in exacerbation of diet-induced atherosclerosis-related arterial remodeling in female monkeys.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗
PubMed1994

Bone functional changes in intact, ovariectomized, and ovariectomized, hormone-supplemented adult cynomolgus monkeys (Macaca fascicularis) evaluated by serum markers and dynamic histomorphometry.

Several parameters of bone mass and function were investigated in three experiments involving intact, ovariectomized, or hormone-supplemented ovariectomized female cynomolgus monkeys. Ovariectomized animals had increased serum levels of alkaline phosphatase and acid phosphatase compared with intact and hormone-supplemented animals. Vertebral bone mass measured ex vivo by dual-photon absorptiometry was reduced by 11-19% in ovariectomized animals compared with intact and hormone-supplemented animals. The most dramatic effects observed with ovariectomy were markedly increased (30-60%) bone formation rates in vertebral cancellous bone, primarily caused by higher activation frequency of basic multicellular units of bone. In addition, combined resorption and reversal periods were decreased and formation period increased in untreated ovariectomized animals. Changes in static histomorphometry parameters were less dramatic, cancellous bone volume being 1-14% lower in ovariectomized animals compared with intact or ovariectomized hormone-supplemented animals. The data indicate that changes in bone resorption are primarily responsible for the lower bone mass of estrogen deficiency and increased bone mass in hormone-supplemented animals. Bone changes in ovariectomized cynomolgus monkeys resemble those in women after menopause and similarly respond positively to hormone supplementation. As such, cynomolgus monkeys are an excellent model for studying the basic mechanisms of osteoporosis and for the development of suitable therapeutic regimens.

Acid Phosphatase↗
PubMed1994

Osteoarthritis in cynomolgus macaques: a primate model of naturally occurring disease.

The objective of the present study was to determine if naturally occurring osteoarthritis of the knee joints that is similar to the condition in humans develops in cynomolgus macaques. Knee joints from 58 young adult (mean age, 7.4 years) female cynomolgus macaques were studied with x-ray densitometry, high-detail radiography, and histology. The animals studied were subjects in a triad designed to examine the effects of the administration of sex steroids on atherosclerosis; except for a control group, the monkeys had been either ovariectomized or treated with sex steroids for 2 years. Therefore, the data were analyzed to determine if these treatments, both of which can influence bone density, affected the severity of osteoarthritis. There was a high prevalence of osteoarthritic lesions, morphologically similar to those seen in humans. Bone changes were more common and severe than cartilage changes and morphologically appeared to precede the cartilage changes. Treatment with testosterone resulted in increased body weight, body mass index, and bone mineral content in the femur and tibia but did not affect the severity of osteoarthritis. These data indicate that naturally occurring osteoarthritis developed in the knee joints of cynomolgus macaques; these animals may be a useful model for the study of osteoarthritis in humans.

Animals↗