Assessing the Effects of Parthenolide on Inflammation, Bone Loss, and Glial Cells within a Collagen Antibody-Induced Arthritis Mouse Model.

Rheumatoid arthritis is characterised by a chronic inflammatory response resulting in destruction of the joint and significant pain. Although a range of treatments are available to control disease activity in RA, bone destruction and joint pain exist despite suppression of inflammation. This study is aimed at assessing the effects of parthenolide (PAR) on paw inflammation, bone destruction, and pain-like behaviour in a mild collagen antibody-induced arthritis (CAIA) mouse model. CAIA was induced in BALB/c mice and treated daily with 1 mg/kg or 4 mg/kg PAR. Clinical paw inflammation was scored daily, and mechanical hypersensitivity was assessed on alternate days. At end point, bone volume and swelling in the paws were assessed using micro-CT. Paw tissue sections were assessed for inflammation and pre-/osteoclast-like cells. The lumbar spinal cord and the periaqueductal grey (PAG) and rostral ventromedulla (RVM) regions of the brain were stained for glial fibrillary acidic protein (GFAP) and ionised calcium-binding adaptor molecule 1 (IBA1) to assess for glial reactivity. Paw scores increased in CAIA mice from days 5-10 and were reduced with 1 mg/kg and 4 mg/kg PAR on days 8-10. Osteoclast-like cells on the bone surface of the radiocarpal joint and within the soft tissue of the hind paw were significantly lower following PAR treatment (p < 0.005). GFAP- and IBA1-positive cells in the PAG and RVM were significantly lower following treatment with 1 mg/kg (p < 0.0001 and p = 0.0004, respectively) and 4 mg/kg PAR (p < 0.0001 and p = 0.001, respectively). In the lumbar spinal cord, IBA1-positive cells were significantly lower in CAIA mice treated with 4 mg/kg PAR (p = 0.001). The findings indicate a suppressive effect of both low- and moderate-dose PAR on paw inflammation, osteoclast presence, and glial cell reactivity in a mild CAIA mouse model.

Ageing Effects on 3-Dimensional Femoral Neck Cross-Sectional Asymmetry: Implications for Age-Related Bone Fragility in Falling.

This paper explores the effects of aging on femoral neck (FN) anatomy in a study of women aged 20-90years in relation to implications for FN fracture propensity in buckling. Five hundred and four participants were scanned by Quantitative Computed Tomography and analyzed using Quantitative Computed Tomography Pro BIT (Mindways). FN cross-section was split through geometric center into superior and inferior sectors. Bone mass, structural measurements, and bone mineral density were analyzed. Buckling ratio was calculated as ratio of buckling radius to cortical thickness. Between 2nd decade and 8th decade, age-related integral bone mass reduction in superior sector was substantially larger than in inferior sector (33% compared to 21%), especially in cortical bone superiorly compared to inferiorly (53% vs 21%; p < 0.001), principally due to reduction in cortical thickness, averaged cortical thickness (56%) with little difference in density. Superior and inferior sector trabecular bone mineral density reduction was similar at 41% and 43% respectively. Differential cortical bone loss in superior sector resulted in a 59% inferior displacement (δ) of center-of-mass from geometric center. Differences in δ and averaged cortical thickness with age accounted for a 151% increase in mean superior buckling ratio from 9 to 23. Analysis confirms significant progressive age-related superior cortical bone loss as the major age effect on FN structure with relative preservation of inferior cortex probably related to maintenance of inferior sector by regular loading as a result of standing and walking. Computation of buckling ratio may allow prediction of fracture propensity in a sideways fall.

Relationships between in vivo dynamic knee joint loading, static alignment and tibial subchondral bone microarchitecture in end-stage knee osteoarthritis.

OBJECTIVE: To study, in end-stage knee osteoarthritis (OA) patients, relationships between indices of in vivo dynamic knee joint loads obtained pre-operatively using gait analysis, static knee alignment, and the subchondral trabecular bone (STB) microarchitecture of their excised tibial plateau quantified with 3D micro-CT. DESIGN: Twenty-five knee OA patients scheduled for total knee arthroplasty underwent pre-operative gait analysis. Mechanical axis deviation (MAD) was determined radiographically. Following surgery, excised tibial plateaus were micro-CT-scanned and STB microarchitecture analysed in four subregions (anteromedial, posteromedial, anterolateral, posterolateral). Regional differences in STB microarchitecture and relationships between joint loading and microarchitecture were examined. RESULTS: STB microarchitecture differed among subregions (P < 0.001), anteromedially exhibiting highest bone volume fraction (BV/TV) and lowest structure model index (SMI). Anteromedial BV/TV and SMI correlated strongest with the peak external rotation moment (ERM; r = -0.74, r = 0.67, P < 0.01), despite ERM being the lowest (by factor of 10) of the moments considered, with majority of ERM measures below accuracy thresholds; medial-to-lateral BV/TV ratios correlated with ERM, MAD, knee adduction moment (KAM) and internal rotation moment (|r|-range: 0.54-0.74). When controlling for walking speed, KAM and MAD, the ERM explained additional 11-30% of the variations in anteromedial BV/TV and medial-to-lateral BV/TV ratio (R2 = 0.59, R2 = 0.69, P < 0.01). CONCLUSIONS: This preliminary study suggests significant associations between tibial plateau STB microarchitecture and knee joint loading indices in end-stage knee OA patients. Particularly, anteromedial BV/TV correlates strongest with ERM, whereas medial-to-lateral BV/TV ratio correlates strongest with indicators of medial-to-lateral joint loading (MAD, KAM) and rotational moments. However, associations with ERM should be interpreted with caution.

Joint loading and proximal tibia subchondral trabecular bone microarchitecture differ with walking gait patterns in end-stage knee osteoarthritis.

OBJECTIVES: To (1) stratify patient subgroups according to their distinct walking gait patterns in end-stage knee osteoarthritis (OA); (2) compare measures of joint loading and proximal tibia subchondral trabecular bone (STB) microarchitecture among these gait subgroups. DESIGN: Twenty-five knee OA patients undergoing total knee arthroplasty (TKA) had pre-operative gait analysis. Following surgery, excised tibial plateaus were micro-CT-scanned and STB microarchitecture analysed in four tibial condylar regions of interest. Peak knee moments were input to k-means cluster analysis, to identify subgroups with homogeneous gait patterns. Joint loading and STB microarchitecture parameters were compared among gait subgroups (Kruskal-Wallis, Bonferroni-corrected Mann-Whitney U tests). RESULTS: Three gait subgroups were revealed: biphasics (n = 7), flexors (n = 9), counter-rotators (n = 9). Peak knee adduction moment (KAM) and KAM impulse were significantly higher (P < 0.05) in biphasics than in flexors and counter-rotators (KAM = -0.65, -0.40 and -0.21 Nm/kg, respectively), suggesting a higher medial-to-lateral tibiofemoral load ratio in biphasics. Interestingly, STB medial-to-lateral bone volume fraction (BV/TV) ratio was also significantly higher (more than double) in biphasics and flexors than in counter-rotators (2.24, 2.00 and 1.00, respectively), whereas in biphasics it was only 10% higher than in flexors and not significantly so. CONCLUSIONS: Within the confines of the limited sample size, data suggests that different mechanisms between the biphasic and flexor gait subroups may generate comparable loads upon the tibial plateau and corresponding bony responses, despite significantly lower KAM indices in flexors. Hence, in flexor gait OA patients, conservative treatments designed to reduce KAM, may not be appropriate. Understanding joint loading among walking gait patterns and relationships to bone microarchitecture may aid at identifying/improving management of persons at risk for developing knee OA.

Quantifying not only bone loss, but also soft tissue swelling, in a murine inflammatory arthritis model using micro-computed tomography.

In rodent models of inflammatory arthritis, bone erosion has been non-invasively assessed by micro-computed tomography (micro-CT). However, non-invasive assessments of paw swelling (oedema) are still based on clinical grading by visual evaluation, or measurements by callipers, not always reliable for the tiny mouse paws. The aim of this work was to demonstrate a novel straightforward 3D micro-CT analysis protocol capable of quantifying not only joint bone erosion, but also soft tissue swelling, from the same scans, in a rodent inflammatory arthritis model. Balb/c mice were divided into two groups: collagen antibody-induced arthritis (CAIA) and CAIA treated with prednisolone, the latter reflecting an established treatment in human rheumatoid arthritis. Clinical paw scores were recorded. On day 10, front paws were assessed by micro-CT and histology. Micro-CT measurements included paw volume (bone and soft tissue together) and bone volume at the radiocarpal joint, and bone volume from the radiocarpal to the metacarpophalangeal joint. Micro-CT analysis revealed significantly lower paw volume (-36%, P < 0.01) and higher bone volume (+17%, P < 0.05) in prednisolone-treated CAIA mice compared with untreated CAIA mice. Paw volume and bone volume assessed by micro-CT correlated significantly with clinical and histological scores (|r| > 0.5, P < 0.01). Untreated CAIA mice showed significantly higher clinical scores, higher inflammation levels histologically, cartilage and bone degradation, and pannus formation, compared with treated mice (P < 0.01). The presented novel micro-CT analysis protocol enables 3D-quantification of paw swelling at the micrometre level, along with the typically assessed bone erosion, using the same images/scans, without altering the scanning procedure or using contrast agents.

Caffeic acid phenethyl ester abrogates bone resorption in a murine calvarial model of polyethylene particle-induced osteolysis.

Particle-induced bone loss by osteoclasts is a common cause of aseptic loosening around implants. This study investigates whether caffeic acid phenethyl ester (CAPE), a potent and specific inhibitor of nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 1 and nuclear factor kappa B, at a low dose reduces bone resorption in a murine calvarial model of polyethylene (PE) particle-induced osteolysis. The effects of particles and CAPE treatment on gastrointestinal tract (GIT) histopathology were also evaluated. Mice were scanned using in vivo animal micro-computed tomography (µCT) as a baseline measurement. PE particles (2.82 × 10(9) particles/mL) were implanted over the calvariae on day 0. CAPE was administered subcutaneously (1 mg/kg/day) at days 0, 4, 7 and 10. Mice were killed at day 14 and serum was analysed for Type-1 carboxyterminal collagen crosslinks (CTX)-1 and osteoclast-associated receptor (OSCAR) levels. Ex vivo µCT scans were conducted to assess bone volume (BV) change and percentage area of calvarial surface resorbed. Calvarial and GIT tissue was processed for histopathology. By day 14, PE particles significantly induced calvarial bone loss compared with control animals as evidenced by resorption areas adjacent to the implanted PE in three-dimensional µCT images, an increase in percentage of resorbed area (p = 0.0022), reduction in BV (p = 0.0012) and increased Tartrate-resistant acid phosphatase positive cells. Serum CTX-1 (p = 0.0495) and OSCAR levels (p = 0.0006) significantly increased in the PE implant group. CAPE significantly inhibited PE particle-induced calvarial osteolysis, as evidenced by a significant reduction in surface bone resorption (p = 0.0012) and volumetric change (p = 0.0154) compared with PE only, but had no effect on systemic CTX-1. Neither particles nor CAPE had an effect on GIT histopathology.

Pre-emptive, early, and delayed alendronate treatment in a rat model of knee osteoarthritis: effect on subchondral trabecular bone microarchitecture and cartilage degradation of the tibia, bone/cartilage turnover, and joint discomfort.

OBJECTIVE: Bisphosphonates are considered potential disease modifying osteoarthritis (OA) agents. The present study investigated the efficacy of pre-emptive, early, and delayed alendronate (ALN) treatment initiation on subchondral trabecular bone and cartilage in low-dose monosodium iodoacetate (MIA)-induced knee OA in rats. METHODS: Male rats received pre-emptive (n = 12, day 0-end of week 2), early (n = 12, end of week 2-end of week 6), or delayed (n = 12, end of week 6-end of week 10) ALN treatment (30 µg/kg/week). Pre-emptive ALN-treated rats were scanned using in vivo micro-computed tomography (micro-CT) after 2 weeks and then sacrificed, early ALN-treated rats were scanned after 2 and 6 weeks and sacrificed, and the delayed ALN-treated rats were scanned after 2, 6, and 10 weeks of OA induction and sacrificed. After sacrifice, bone histomorphometry and histology of the tibia and biomarker analyses were undertaken. Changes in hind limb weight-bearing were assessed from day -1 until day 14. RESULTS: MIA-induced pathological features similar to progressive human OA in the cartilage and subchondral bone. Pre-emptive ALN treatment preserved subchondral trabecular bone microarchitecture, prevented bone loss, decreased bone turnover and joint discomfort. Pre-emptive ALN treatment had moderate effects on cartilage degradation. Early and delayed ALN treatments prevented loss of trabeculae and decreased bone turnover, but had no significant effect on cartilage degradation. CONCLUSION: ALN prevented increased bone turnover and preserved the structural integrity of subchondral bone in experimental OA. The time point of treatment initiation is crucial for treating OA. Treating both the subchondral bone and cartilage in OA would be clinically more beneficial.

Human bone material characterization: integrated imaging surface investigation of male fragility fractures.

UNLABELLED: The interrelation of calcium and phosphorus was evaluated as a function of bone material quality in femoral heads from male fragility fracture patients via surface analytical imaging as well as scanning microscopy techniques. A link between fragility fractures and increased calcium to phosphorus ratio was observed despite normal mineralization density distribution. INTRODUCTION: Bone fragility in men has been recently recognized as a public health issue, but little attention has been devoted to bone material quality and the possible efficacy in fracture risk prevention. Clinical routine fracture risk estimations do not consider the quality of the mineralized matrix and the critical role played by the different chemical components that are present. This study uses a combination of different imaging and analytical techniques to gain insights into both the spatial distribution and the relationship of phosphorus and calcium in bone. METHODS: X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry imaging techniques were used to investigate the relationship between calcium and phosphorus in un-embedded human femoral head specimens from fragility fracture patients and non-fracture age-matched controls. The inclusion of the bone mineral density distribution via backscattered scanning electron microscopy provides information about the mineralization status between the groups. RESULTS: A link between fragility fracture and increased calcium and decreased phosphorus in the femoral head was observed despite normal mineralization density distribution. Results exhibited significantly increased calcium to phosphorus ratio in the fragility fracture group, whereas the non-fracture control group ratio was in agreement with the literature value of 1.66 M ratio in mature bone. CONCLUSIONS: Our results highlight the potential importance of the relationship between calcium and phosphorus, especially in areas of new bone formation, when estimating fracture risk of the femoral head. The determination of calcium and phosphorus fractions in bone mineral density measurements may hold the key to better fracture risk assessment as well as more targeted therapies.

Prolonged COVID 19 Outbreak and Psychological Response of Nurses in Italian Healthcare System: Cross-Sectional Study.

Aim of the study was to analyze the posttraumatic stress disorder risk nurses, detecting the relationship between distress experience and personality dimensions in Italian COVID-19 outbreak. A cross-sectional study was conducted based on 2 data detection (March 2020 and September 2020). Mental evaluation was carried out in Laboratory of Clinical Psychology on n.69 nurses in range age 22-64 years old (mean age 37.3; sd ± 10.3; 55% working in nursing care with confirmed COVID-19 patients (named frontline; secondline nurses have been identified by nursing care working with infectious patients but no confirmed COVID-19). Measurement was focused on symptoms anxiety, personality traits, peritraumatic dissociation and post-traumatic stress for all participants. No online screening was applied. Comparisons (ANOVA test) within the various demographic characteristics demonstrated few significant differences between groups on DASS-21, PDEQ, and ISE-R scores. Correlation analysis (Spearman test) was performed among PDEQ, DASS-21, BFI-10 and IES-R and confirmed between anxiety (DASS-21) and peritraumatic dissociation and post-traumatic stress; then anxiety is positively correlated to agreeableness variable of BFI-10 test. The emotional distress was protracted overtime (after 6 months) but in long-term personality traits resulted mediator facing subjective stress. Our finding drew details for protective and predictive risk factors as well as mental health issues of nurses dealing with pandemic: healthcare workers faced the protracted challenge caring COVID-19 patients over and over again: in short time the impact was relevant, and the prolonged exposition to the stressor was tackled by personal resources such as personality traits.

Critical molecular regulators, histomorphometric indices and their correlations in the trabecular bone in primary hip osteoarthritis.

OBJECTIVE: This study examined differential gene expression, histomorphometric indices and relationships between these, in femoral trabecular bone from osteoarthritis (OA) patients and control (CTL) subjects, with the aim of identifying potential molecular drivers consistent with changes in structural and remodelling indices in the OA pathology. MATERIALS AND METHODS: Bone samples from the intertrochanteric (IT) region were obtained from age and sex-matched cohorts of 23 primary hip OA patients and 21 CTL subjects. Real-time polymerase chain reaction (PCR) and histomorphometric analysis were performed on each sample and correlations between gene expression and histomorphometric variables determined. RESULTS: Alterations in gene expression, structural indices and correlations between these were found in OA bone compared to CTL. In OA bone, expression of critical regulators of osteoblast differentiation (TWIST1) and function (PTEN, TIMP4) were decreased, while genes associated with inflammation (SMAD3, CD14) were increased. Bone structural and formation indices (BV/TV, Tb.N, OS/BS) were increased, whereas resorption indices (ES/BS, ES/BV) were decreased. Importantly, significant correlations in CTL bone between CTNNB1 expression and formation indices (OS/BS, OS/BV, OV/BV) were absent in OA bone, indicating altered WNT/ß-catenin signalling. TWIST1 expression and BV/TV were correlated in CTL bone, but not in OA bone, consistent with altered osteoblastogenesis in OA. Matrix metalloproteinase 25 (MMP25) expression and remodelling indices (ES/BS, ES/BV, ES/TV) were correlated only in OA pointing to aberrant bone remodelling in this pathology. CONCLUSIONS: These findings indicate an altered state of osteoblast differentiation and function in OA driven by several key molecular regulators. In association with this differential gene expression, an altered state of both trabecular bone remodelling and resulting microarchitecture were also observed, further characterising the pathogenesis of primary hip OA.

Detecting early bone changes using in vivo micro-CT in ovariectomized, zoledronic acid-treated, and sham-operated rats.

SUMMARY: This study monitored in vivo the effect on bone microarchitecture of initiating antiresorptive treatment with zoledronic acid in rats at 2 weeks following ovariectomy, an early phase at which major degenerative bone changes have been found to occur. The treatment still facilitated the full reversal of cancellous bone loss in rat tibia, highlighting the importance of the time point of initiation of antiresorptive treatment. INTRODUCTION: Injection of zoledronic acid in rats at time of ovariectomy has been found to fully preserve tibial bone microarchitecture over time, whereas injection at 8 weeks after ovariectomy has shown partial bone recovery. This study investigated the effect on microarchitecture of initiating antiresorptive treatment in the early phase following ovariectomy, at 2 weeks, a time point at which major degenerative changes in the bone have been found to occur. METHODS: Female Sprague-Dawley rats were divided into ovariectomized group, ovariectomized group treated with zoledronic acid, and sham-operated group. In vivo micro-CT scanning of rat tibiae and morphometric analysis were performed at 0, 2, 4, 8, and 12 weeks after ovariectomy, with zoledronic acid treatment beginning 2 weeks after ovariectomy. Data were first analyzed with repeated measures analysis of variance (longitudinal study design) and then without repeated measures (cross-sectional study design). RESULTS: The ovariectomized group demonstrated dramatic bone loss, first detected at week 2. Conversely, at week 4, the zoledronic acid-treated group returned microstructural parameters to baseline values. Remarkable increases in bone parameters were found after 6 weeks of treatment and maintained similar to sham group until the end. The longitudinal study design provided earlier detection of bone changes compared to the cross-sectional study design. CONCLUSIONS: Treatment with zoledronic acid as late as 2 weeks after ovariectomy still facilitates the full reversal of cancellous bone loss in the rat tibia.

Quality control protocol for in vitro micro-computed tomography.

The aim of this work was to present and discuss a quality control protocol for in vitro micro-computed tomography (microCT), based on the adaptation of the quality control protocols for medical computed tomography. The importance of establishing a quality control protocol is related to the opportunity to identify problems on time comparing the microCT images acquired in different time points, and in this way to verify the performance of the device. The proposed quality control protocol was applied for a long-time monitoring period to verify the stability of the micro-tomographic system over time. The protocol proposed in this study was applied to the histomorphometric characterization of bone tissue, but it can be used on a wide range of in vitro microCT applications. Noise and uniformity tests, taken and adapted to micro-tomographic system by medical standard guidelines of quality control, were performed by the use of a water phantom. An accuracy test was designed and performed by the use of a morphometric calibrated phantom. All these tests were performed during a long-time monitoring period to control the stability of the system. Specific control charts and monitoring parameters for each test were used to represent the monthly measures collected during 20 months and an out of control condition was defined. The reference values (baseline), calculated to control the stability of micro-tomographic system over time, were calculated during acceptance/status test. During the period, no out of control conditions in noise, uniformity and accuracy tests were recorded. However, a changing condition was found in noise test, as showed by using statistical C (P < 0.01) and Kruskal-Wallis (P < 0.05) tests. In particular, a Wilcoxon rank sum test with Bonferroni correction (P < 0.0125) was applied in noise test to investigate which of the comparisons among first five acquisitions of year 2004 (group B.L.) and each group was significant (P < 0.0125). The noise showed a slight but significant increase over the years compared to baseline value; however, no out of control conditions were recorded. Nonetheless, a maintenance service to control the performance of mechanical components of microCT was required and performed.

Dependence of mechanical compressive strength on local variations in microarchitecture in cancellous bone of proximal human femur.

Human cancellous bone is a heterogeneous material. Despite this, most of the published studies report correlations between mechanical properties and morphometric parameters averaged on the whole specimen. This work investigated whether local variations in morphometric parameters were linked to the localized failure regions of cancellous bone. Additionally, it was examined whether local values of morphometric parameters can predict the ultimate stress better than the average bone volume fraction (BV/TV). Cylindrical cancellous bone specimens extracted along the primary compressive group of human femoral heads were studied. These were microCT-imaged to assess the morphometric parameters, compressed to determine the ultimate stress, and rescanned by microCT to visualize the failure region. Failure involved slightly less than half of the free height of the specimens. Significant differences were found in the morphometric parameters calculated in the failure and in the non-failure regions. The cross-sections containing minimum BV/TV values were those most often located inside the failure region (83%, p<0.001). Regression analysis confirmed that variations in BV/TV best describe variations in ultimate stress (R2=0.84) out of the averaged morphometric parameters. The prediction of ultimate stress increased when minimum or maximum values of the morphometric parameters were taken, with the highest prediction found by considering the minimum BV/TV (R2=0.95). In conclusion, due to the heterogeneity of cancellous bone, there may exist regions characterized by a different microarchitecture, where the bone is weaker and consequently is more likely to fail. These regions mostly contain minimum values in BV/TV, which were found to predict ultimate stress better than average BV/TV.

Emotional "Patient-Oriented" Support in Young Patients With I-II Stage Breast Cancer: Pilot Study.

Objective: The recent increased survival rate after breast cancer (BC) diagnosis and treatment is mostly related to early screening in younger age. Evidence gained from newly detected assessed psychological needs as well as certain emotional regulatory patterns in younger survivors has been related in the literature to an extremely low rate of adherence to the psychological therapies offered. Tailored psychological support is necessary. The aim of the present study was to verify the preliminary efficacy of supportive psychological intervention with an innovative orientation: the Early BC Psychological Intervention (EBC-Psy). Methods: A controlled study design was used to investigate the efficacy of EBC-Psy intervention. Preliminary data involved twenty-four patients in the age range of 35-50 years, diagnosed with cancer at the early stage (I-II), who were exposed to the EBC-Psy intervention. To address the effect of intervention, emotional variables were tested before the treatment (Time 1) and then again after 6 months of the treatment (Time 2); evaluated emotional dimensions were anxiety, anger, depression, and psychological distress. Results: EBC-Psy intervention appears to be effective on both depression (p = 0.02) and psychological distress (p = 0.01), even in a short time, highlighting the strength of a reinforced positive psychological conceptual approach to deal with the "disease condition" in younger patients; on the contrary, the control group evidenced an increase in the same emotional variables in timing. Conclusion: Our findings, even if limited by this small-scale protocol, seemed to confirm the role of positive psychotherapy after BC diagnosis and treatment through the impact of cognitive processes, coping strategies, and psychological resilience. Future theoretical framework could boost the intervention to design an innovative survivorship model.

Structural parameters and mechanical strength of cancellous bone in the femoral head in osteoarthritis do not depend on age.

For normal bone, aging has been associated with a decrease of both density and failure strength, and with the development of pathologies such as osteoporosis. Conversely, it has been reported that another common disease, osteoarthritis, may alter these age-related changes in cancellous bone, suggesting that it may have a protective role against osteoporosis and the correspondent fracture risk. It was reported that in the principal compressive region of the femoral head in osteoarthritis the bone density does not depend on age. However, it is not clear if this independence on age of the cancellous bone density corresponds also to a reduced dependence on age of the strength to failure. The present work examined cancellous bone from the principal compressive region of the femoral head of 37 patients having severe osteoarthritis. The aim was (1) to investigate the dependence on age of both the structural parameters and the ultimate stress and (2) to investigate the relationships between the ultimate stress and the structural parameters. Using X-ray microcomputed tomography, three-dimensional structural parameters, such as bone volume fraction, direct trabecular thickness and structure model index were calculated. Then the specimens were compressed to failure to determine the ultimate stress. It was found that none of the investigated structural parameters did depend on age, and also the ultimate stress did not depend on age (p>0.05 for all regressions on age). In addition, the ultimate stress was significantly correlated with the structural parameters, primary with the minimum bone volume fraction and the average bone volume fraction (R(2)=0.95 and R(2)=0.84, respectively). These findings show that severe osteoarthritis or a related factor may change the age dependences of both the structural parameters and the mechanical properties usually reported for normal cancellous bone. These results suggest for this pathology to have a protective role against the age-related decrease in density, the age-related deterioration of the microarchitecture and the age-related decrease of the failure strength for the cancellous bone in the principal compressive region of the human femoral head.

Transglutaminase activity in rat liver after acute ethanol administration.

The acute effect of ethanol on hepatic transglutaminase (EC 2.3.2.13) activity and polyamine levels were investigated in the rat. A high dose of ethanol (5 g/kg body weight, given by gastric intubation) caused in homogenate and cytosolic fraction an inhibition of 50-70% from 3 to 24 h which thereafter was reversible. Such a decrease may be in part responsible for the observed enhancement in putrescine and spermidine contents observed at the same times. Pyrazole, an inhibitor of alcohol dehydrogenase, prevented the ethanol-induced reduction in transglutaminase activity. Disulfiram, an inhibitor of aldehyde dehydrogenase, allowed detection of an inhibitory effect on enzyme activity even at a low dose of ethanol (2 g/kg), which per se did not modify transglutaminase activity. The hepatic cytosolic fraction, incubated in the presence of various concentrations of acetaldehyde, showed a dose-dependent inhibition of transglutaminase activity. All of these results suggest that acetaldehyde, the first and toxic metabolite of ethanol, inhibits hepatic transglutaminase activity, probably by its binding to the active thiol site of the enzyme. The reduction in transglutaminase may lead to an alteration of cytoskeleton, since the enzyme is known to be involved in tubuline polymerization and microfilament assembly.

Lp(a) in hypertensive patients.

Lipoprotein(a) (Lp(a)) is considered an important risk factor for coronary disease, cerebrovascular pathology and re-stenosis of coronary bypass. Few studies have been conducted on this lipoprotein in essential arterial hypertensive patients. The purpose of our study was to measure the serum concentrations of Lp(a) and the main parameters of the lipid profile in a group of essential hypertensive patients not receiving pharmacological treatment and with no clinical signs of associated pathologies or organ damage. A total of 123 Caucasian essential arterial hypertensive patients (47 men and 76 women) were studied and compared with 89 controls (36 men and 53 women) matched in terms of age, sex, body mass index (BMI) and smoking habits. It was found that the hypertensive patients had higher plasma concentrations of Lp(a), total cholesterol (TC), triglycerides (TG) and very low density lipoprotein (VLDL-C) than controls (P < 0.01), with no differences in the plasma concentrations of Lp(a) between the two sexes. Only 10 hypertension patients and seven controls had plasma concentrations of Lp(a) of over 30 mg/dl. Lp(a) does not correlate with the main parameters of the lipid profile. We can confirm that hypertension and dyslipidaemia, which are two of the main risk factors for vascular diseases on an atherosclerotic basis, are often associated. However, higher plasma concentrations of Lp(a), albeit within the normal range, could be an independent risk factor for atherosclerosis, and could contribute towards increasing the incidence of cardiovascular disease in people with essential arterial hypertension.

Isolated office hypertension: are there any markers of future blood pressure status?

BACKGROUND: The introduction of ambulatory blood pressure monitoring into clinical practice has defined a clinical condition called 'isolated office hypertension'. OBJECTIVE: The aim of this study was to evaluate the long-term systolic and diastolic blood pressure changes in patients with isolated office hypertension and to identify the presence of markers capable of identifying which patients will develop sustained hypertension. METHODS: All the 407 patients enrolled had a random office systolic or/and diastolic blood pressure of over 140/90mmHg and a mean daytime ambulatory blood pressure of 130/84mmHg or less. At enrollment, each patient underwent a 'baseline examination' made up of a physical evaluation, a 24h ambulatory blood pressure monitoring, and a mental arithmetic test performed at the end of the 24h ambulatory monitoring. RESULTS: Of the 173 patients finally studied, 102 (58.9%) developed sustained hypertension with an increase in both ambulatory systolic and diastolic blood pressure. At the time of the baseline examination, the patients were divided into two groups. Group A included patients with mean ambulatory systolic and diastolic blood pressures in the first hour of 130/84mmHg or less; group B included patients with mean ambulatory systolic and diastolic pressures in the first hour of greater than 130/84mmHg. During the mental arithmetic test, the systolic and heart rate values increased significantly only in group B patients. Of the 102 patients who had become hypertensive by the time of the follow-up examination, 84 (82%) belonged to group B. CONCLUSION: These data suggest that isolated office hypertension may indeed be a transitional state towards the development of sustained hypertension. Moreover, the mean ambulatory blood pressure value during the first hour can be considered to be a marker of a higher risk of developing sustained hypertension.

Elastic properties and structure of the radial artery in patients with type 2 diabetes.

Alterations of elastic properties may contribute to the accelerated atherosclerosis in patients with T2D. Little is known, however, about radial artery distensibility in this patient group. A total of 19 patients with T2D and 19 controls were investigated.An echotracking system coupled to a plethysmograph was used to assess the morphologic and elastic properties of radial artery. Distensibility and compliance were evaluated using Langewouters' equations. Distensibility and compliance did not differ significantly in patients with diabetes compared with controls. In contrast, radial IMT and WCSA were significantly higher in patients with T2D than in controls. Multiple regression analyses revealed a significant association between SBP and IMT (r(2) = 0.40, p<0.001) as well as WCSA (r = 0.54; r(2) = 0.30; p<0.001 ) in individuals with diabetes. In conclusion, distensibility and compliance of the radial artery are not reduced in patients with T2D. In contrast, radial IMT and WCSA are significantly higher in patients with T2D than in controls.These modifications are chiefly and positively related to SBP.