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Remote ischemic conditioning (RIC), brief repetitive cycles of ischemia and reperfusion in remote tissues, is known to induce robust protection against myocardial ischemia-reperfusion (I/R) injury in preclinical studies. However, translation of the beneficial effects to the clinical setting has been challenging. A possibility is that comorbidities, including hypercholesterolemia, interfere with the protective mechanisms of RIC. The aim of this study was to test if hypercholesterolemia attenuates the efficacy of RIC in patients with hypercholesterolemia. Patients with familial hypercholesterolemia (FH) with high (≥5.5 mmol/L) low-density lipoprotein cholesterol (LDL-C), FH with low (≤2.5 mmol/L) and healthy control subjects (

Lipoprotein(a) [Lp(a)] is a causal cardiovascular risk factor recommended to be measured at least once in a lifetime. We aimed to establish the association between routinely measured Lp(a) levels and the development of incident calcified aortic valve stenosis (CAVS).This retrospective registry based observational study includes all individuals who had their Lp(a) measured in clinical routine between 2003 and 2017 at Karolinska University Laboratory, Stockholm. Data on pre-existing medical conditions, pharmacological treatment and outcomes were retrieved from national patient registries.The study comprised 23,298 individuals of which 489 received a CAVS diagnosis during the study period. The CAVS group (71 ± 11 years, 62% males) had a larger cardiovascular burden than the group without CAVS (55 ± 17 years and 48% males). Individuals with CAVS had higher Lp(a) 90th percentile (117 mg/dL or 249 nmol/L) than those without (89 mg/dL or 179 nmol/L) (p 0.001), a difference seen in both sexes. The incident rates of CAVS per 10,000 person-years was 22.3 for individuals at90th Lp(a) percentile compared to 12.8 for the 0Lp(a) measured in the clinical routine is higher in individuals with CAVS. An Lp(a) level above90th percentile is associated with the development of incident CAVS during a 14-year observational period.

OBJECTIVE Patients with diabetes or familial hypercholesterolemia (FH) have an increased incidence of cardiovascular diseases compared with the population, but whether this risk is exacerbated in patients with combined traits is unknown. RESEARCH DESIGN AND METHODS In this Swedish nationwide, register-based cohort study, patients with diabetes were included between 2002 and 2020. Adjusted Cox proportional hazards models were used to assess the risk of cardiovascular events in patients with or without phenotypic FH (≥6 points for phenotypic FH according to Dutch Lipid Clinic Network criteria) compared with general population control subjects without diabetes as reference. RESULTS A total of 45,585 patients with type 1 diabetes (227,923 control subjects) and 655,250 patients with type 2 diabetes (655,250 control subjects) were followed for a median of 14.1 and 7.9 years, respectively. Of those, 153 and 7,197, respectively, had phenotypic FH. Compared with control subjects, patients with diabetes and phenotypic FH had higher risk of cardiovascular mortality (type 1: hazard ratio 21.3 [95% CI 14.6–31.0]; type 2: 2.40 [2.19–2.63]) and of a cardiovascular event (type 1: 15.1 [11.1–20.5]; type 2: 2.73 [2.58–2.89]). Further, patients with diabetes and phenotypic FH had higher LDL-cholesterol levels during observation (P < 0.05) and increased risk of all major cardiovascular outcomes (P < 0.0001) than patients with diabetes but without FH. The proportion receiving lipid-lowering treatment was higher in patients with phenotypic FH (P < 0.0001). CONCLUSIONS Patients with both diabetes and phenotypic FH are more at risk for adverse cardiovascular outcomes and have higher LDL-cholesterol levels despite receiving intensified lipid-lowering therapy.

Aims To investigate plasma lipoprotein(a) [Lp(a)] levels measured in routine clinical care and their association with mortality and cardiovascular disease. Methods and results This retrospective registry-based observational cohort study includes all individuals with plasma Lp(a) results measured at the Karolinska University Laboratory 2003–17. Outcome data were captured in national outcome registries. Levels of Lp(a) expressed in mass or molar units were examined separately. In adjusted Cox regression models, association between deciles of plasma Lp(a) concentrations, mortality, and cardiovascular outcomes were assessed. A total of 23 398 individuals [52% females, mean (standard deviation) age 55.5 (17.2) years, median Lp(a) levels 17 mg/dL or 19.5 nmol/L] were included. Individuals with an Lp(a) level >90th decile (>90 mg/dL or >180 nmol/L) had hazard ratios (95% confidence interval) of 1.25 (1.05–1.50) for major adverse cardiovascular events (P = 0.013), 1.37 (1.14–1.64) for atherosclerotic cardiovascular disease (P = 0.001), and 1.62 (1.28–2.05) for coronary artery disease (P ≤ 0.001), compared to individuals with Lp(a) ≤50th decile. No association between Lp(a) and mortality, peripheral artery disease, or ischaemic stroke was observed. Conclusion High Lp(a) levels are associated with adverse cardiovascular disease outcomes also in individuals with Lp(a) measured in routine clinical care. This supports the 2019 ESC/EAS recommendation to measure Lp(a) at least once during lifetime to assess cardiovascular risk and implies the need for intensive preventive therapy in patients with elevated Lp(a).

Based on separate protective mechanisms related to lipid metabolism, viral cell entry and inflammation, fibrate treatment might be advantageous among patients who have been taking fibrates before SARS-CoV-2 infection and continue taking them during the infection. Based on published data on hospitalized COVID-19 patients, we recommend that the clinicians should ask their patients with metabolic syndrome who are already taking fibrates to continue fibrate treatment during the COVID-19 illness. This recommendation applies to both outpatients and hospitalized patients. However, results from the ongoing randomized controlled trials (RCTs) using fenofibrate treatment for the prevention or treatment of COVID-19 have yet to prove that fenofibrate is clinically significant for this indication.KEY MESSAGESThe role of fibrates as a repurpose to treat SARS-CoV-2 is under investigation in at least three ongoing RCTs.Obesity, diabetes, hypertension and dyslipidaemia, individually or clustered as a discrete phenotype, the metabolic syndrome, typically associate with a more severe course of COVID-19.Fibrate treatment seems to be most advantageous among patients who have been taken fibrates before SARS-CoV-2 infection and are continuing to take them during the infection.We recommend that the clinicians encourage their patients who are already taking fibrate to continue using the drug throughout the COVID-19 illness.

Background and aims In familial hypercholesterolemia (FH), statin treatment should be considered from 8 to 10 years of age, but the prevalence of statin use among children is not known. Methods Statin use (2008–2018) among children aged 10–14 and 15–19 years was obtained from the national prescription databases in Norway, Sweden and Denmark. We assumed that all statin users in these age groups had FH, and that the estimated prevalence of FH is 1 in 250 inhabitants. Changes in prevalence rates of statin use between 2008 and 2018 by country, age and sex were estimated using the Joinpoint Regression Program version 4.8.0.1. Differences in prevalence rate ratio each year between countries were analyzed using Poisson regression. Results Among children aged 10–14 years, there was a significant increase in statin use in Norway and Denmark between 2008 and 2018, while in Sweden an increase was only seen after 2014. Among children aged 15–19 years, an increase in statin use was only observed in Norway and Sweden between 2008 and 2018. Statin use was significantly more prevalent in Norway than in Sweden and Denmark each year, and in 2018 the proportion of children using statins was 4–5 times (10–14 years) and 3 times (15–19 years) higher in Norway compared with Sweden and Denmark. In 2018 in Norway, 19% and 35% of children aged 10–14 years and 15–19 years estimated to have FH used statins respectively; corresponding percentages in Sweden were 4.5% and 10%, and in Denmark 3% and 12%. In Norway, the increase in statin use between 2008 and 2018 roughly corresponded to the increase in children with genetically verified FH. Conclusions Between 2008 and 2018, statin use increased in children aged 10–19 years in Norway, Sweden and Denmark, but with large differences between the countries; statin use was 3–5 times more prevalent in Norway than in Sweden and Denmark, which may be due to a more widespread use of genetic testing for FH in Norway.

Familial hypercholesterolemia (FH) is an autosomal dominant hereditary dyslipidemia that leads to high plasma cholesterol levels and a severely increased risk for premature cardiovascular disease. Early primary prevention with lipid lowering drugs can markedly reduce this risk. FH is underdiagnosed in Sweden. With a prevalence of 1:311, approximately 33 000 individuals in Sweden are expected to have FH but only a small percentage have been diagnosed up until now. We developed a digiphysical cascade screening model to diagnose FH in relatives of an index case with a confirmed pathogenic mutation in a FH disease gene. It has the potential to provide high-throughput and effective screening and the work model is now part of the clinical routine care at Karolinska University Hospital.

Background/Introduction Remote ischemic conditioning (RIC) is the action of brief periods of ischemia to a remote tissue and has been suggested to protect against myocardial ischemia-reperfusion (IR) injury. The outcomes of clinical trials in terms of clinical endpoints and infarct size reduction have been variable, which may be related to influence of comorbidities on the effect of RIC. Animal studies suggest that hypercholesterolemia attenuates the cardioprotective effect of RIC, but no data from study on patients are available. Hence, our aim was to investigate the response of RIC on IR-induced endothelial dysfunction in patients with familial hypercholesterolemia (FH). Purpose To investigate if RIC protects against endothelial dysfunction induced by IR in patients with FH with high (≥5.5 mmol/L) and low (≤2.5 mmol/L) LDL-cholesterol levels. Methods All subjects with FH (n=12) with LDL ≥5.5 mmol/L, FH with LDL Results Plasma mean LDL-cholesterol was significantly higher in the FH group with high LDL (6.6±1.4 mmol/L) compared to the control group (2.4±0.7 mmol/L; p Conclusion These observations suggest that RIC, which protects from IR-induced endothelial dysfunction in healthy controls, fails to protect from IR-induced endothelial dysfunction in patients with FH and LDL-cholesterol >5.5 mmol/L. The protective effect of RIC is restored after treatment of hypercholesterolemia. This finding may have bearings on the clinical efficacy of RIC in patients with ST-elevation myocardial infarction. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Heart-lung foundation

OBJECTIVE To investigate the association of the cardiovascular risk factor lipoprotein (Lp)(a) and vascular complications in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS Patients with type 1 diabetes receiving regular care were recruited in this observational cross-sectional study and divided into four groups according to their Lp(a) levels in nmol/L (very low 120). Prevalence of vascular complications was compared between the groups. In addition, the association between metabolic control, measured as HbA1c, and Lp(a) was studied. RESULTS The patients (n = 1,860) had a median age of 48 years, diabetes duration of 25 years, and HbA1c of 7.8% (61 mmol/mol). The median Lp(a) was 19 (interquartile range 10–71) nmol/L. No significant differences between men and women were observed, but Lp(a) levels increased with increasing age. Patients in the high Lp(a) group had higher prevalence of complications than patients in the very low Lp(a) group. The age- and smoking-status–adjusted relative risk ratio of having any macrovascular disease was 1.51 (95% CI 1.01–2.28, P = 0.048); coronary heart disease, 1.70 (95% CI 0.97–3.00, P = 0.063); albuminuria, 1.68 (95% CI 1.12–2.50, P = 0.01); and calcified aortic valve disease, 2.03 (95% CI 1.03–4.03; P = 0.042). Patients with good metabolic control, HbA1c 6.9% (>52 mmol/mol). CONCLUSIONS Lp(a) is a significant risk factor for macrovascular disease, albuminuria, and calcified aortic valve disease in patients with type 1 diabetes. Poor metabolic control in patients with type 1 diabetes is associated with increased Lp(a) levels.

We have previously shown increased vascular reactivity to angiotensin (Ang) II in familial combined hyperlipidemia. However, this has not been well studied in familial hypercholesterolemia (FH), a condition with incipient endothelial dysfunction. This study aimed to examine microvascular and macrovascular responses to Ang II in FH. Therefore, we investigated the effects of a 3-hour infusion of Ang II on blood pressure and forearm skin microvascular function in 16 otherwise healthy patients with FH and matched healthy controls. Skin microvascular hyperemia was studied by laser Doppler fluxmetry during local heating. Microvascular resistance was determined by the ratio of mean arterial pressure to microvascular hyperemia. Macrovascular reactivity was assessed by changes in brachial blood pressure. Compared with the controls, the FH group had increased baseline systolic blood pressure (127 ± 14 vs. 115 ± 12 mm Hg; P = 0.02), while systolic blood pressure responses were similar (+24 ± 9 vs. +21 ± 7 mm Hg; P = 0.26) after 3 hours of Ang II infusion. At baseline, there were no group differences in microvascular hyperemia or resistance. However, after 3 hours of Ang II infusion, heat-induced microvascular hyperemia was less pronounced in FH (126 ± 95 vs. 184 ± 102 arbitrary units; P = 0.01), while microvascular resistance during heat-induced hyperemia was increased (1.9 ± 0.9 vs. 0.9 ± 0.8, P = 0.01), as compared to controls. Both these responses were further pronounced 1 hour after stopping Ang II. In conclusion, despite similar blood pressure responses to Ang II in the FH group and controls, microvascular dilatation capacity was impaired in the FH group, indicating endothelial dysfunction. These findings and increased microvascular resistance may lead to hypertension and microvascular complications in FH.

Background Lipoprotein(a) [Lp(a)] is a cardiovascular risk factor that has been shown to correlate to cardiovascular disease and aortic valve disease. Plasma levels of Lp(a) has a skewed distribution, is highly influenced by genetic inheritance and is not considered to be affected by age, sex or lifestyle. Its importance for the development of vascular complications in patients with type 1 diabetes is unknown. Purpose To assess the contribution of Lp(a) to cardiovascular disease, microvascular complications, aortic valve disease in patients with type 1 diabetes mellitus, and to assess the relationship between diabetes metabolic control and Lp(a) levels. Methods We included 1857 consecutive type 1 diabetes patients receiving regular care at our out-patient clinic, department of Endocrinology, into an observational cross sectional registry study. Patient characteristics, cardiovascular history and Lp(a) measurement was extracted from their electronic medical charts. Patients were divided into four groups according to their Lp(a) levels in nmol/L (Very Low 120) and statistical analysis was performed comparing the prevalence of mikro- and makrovascular complications between the groups. The relationship between Lp(a) and diabetes control measured as HbA1c (mmol/mol) was studied by comparing the subgroups with good (70) metabolic control. Results The mean (SD) age and diabetes duration in the cohort was 49.9 (15.8) years and 26.7 (15.5) years, respectively, and the Lp(a) median (inter quartile range) was 20.4 (7.8–75.1) nmol/L. Patients in the high Lp(a) group had significantly higher prevalence of cardiovascular and microvascular complications compared to patients with very low levels. The relative risk (confidence interval) increase to be affected by ischemic heart disease was 2.42 (1.41–4.15) (p=0.001), by albuminuria 1.87 1.26–2.78) (p=0.002) and by aortic valve disease 2.96 (1.53–5.78) (p=0.001). The relationship between Lp(a) and vascular complications was sustained when data was adjusted for age and smoking status between the groups albeit at a weaker level. No significant relationship was detected between cerebrovascular disease or the microvascular complications retinopathy and neuropathy and Lp(a) levels. Significantly higher Lp(a) levels were observed in patients with poor and average metabolic control compared to patients with good control (p Figure 1. Lp(a) levels in relation to HbA1c Conclusions Lp(a) is a significant risk factor for cardiovascular complications and aortic valve disease in patients with type 1 diabetes. Poor metabolic control of the diabetes disease is associated to high Lp(a) levels. Acknowledgement/Funding Swedish Heart Foundation (PP), The Swedish Research Council (PP), Karolinska Institutet (PP, JB), Investigator initiated study grant from Sanofi (JB)

At the turn of the year 2018/19, a new ICD-10 code (E78.0A) will be introduced in Sweden for the hereditary blood lipid disorder familial hypercholesterolemia (FH). Patients with FH have a significantly increased risk of developing atherosclerotic disease, such as myocardial infarction before the age of 50. However, early diagnosis and start of treatment of FH can ameliorate the disease's negative long term effects. The Swedish National Board of Health and Welfare gave in its guidelines from 2015 a high priority to the work of identifying and diagnosing individuals with FH in the general population. The introduction of the ICD-10 code E78.0A for FH may, when properly used, be an effective tool in this work.

BackgroundNew evidence shows that high density lipoproteins (HDL) have protective effects beyond their role in reverse cholesterol transport. Reconstituted HDL (rHDL) offer an attractive means of clinically exploiting these novel effects including cardioprotection against ischemia reperfusion injury (IRI). However, basic rHDL composition is limited to apolipoprotein AI (apoAI) and phospholipids; addition of bioactive compound may enhance its beneficial effects.ObjectiveThe aim of this study was to investigate the role of rHDL in post-ischemic model, and to analyze the potential impact of sphingosine-1-phosphate (S1P) in rHDL formulations.Methods and resultsThe impact of HDL on IRI was investigated using complementary in vivo, ex vivo and in vitro IRI models. Acute post-ischemic treatment with native HDL significantly reduced infarct size and cell death in the ex vivo, isolated heart (Langendorff) model and the in vivo model (-48%, pConclusionHDL afford protection against IRI in a clinically relevant model (post-ischemia). rHDL is significantly protective if supplemented with S1P. The protective impact of HDL appears to target directly the cardiomyocyte.

We determined the efficacy of a back muscle extensor strengthening program on the back muscle extensor strength, kyphosis, height and thoracic expansion in women with at least one vertebral fracture, kyphosis and osteoporosis. Thirty-six patients were included and randomized to a control or a training group. The training focused on back muscle extensor strengthening program for 1 h, twice a week for 4 months and was performed by a physiotherapist. The main outcome measure was the back muscle extensor strength. In an intention-to-treat analysis no significant effects on back muscle strength in the training group vs. controls could be seen (p = 0.74). In a per-protocol analysis (n = 28), the training group increased back muscle strength from 290 ± 87 to 331 ± 89 N while the control group showed no improvement. After adjusting for the strength at baseline, a significant effect of training could be demonstrated (p = 0.029). When comparing the heights between the groups a significant group × time interaction was observed (p = 0.012) where the training women increased their mean height with 0.3 cm (p = 0.101) and controls decreased 0.44 cm (p = 0.045). The training group improved their thoracic expansion compared with baseline (p = 0.03). No effect of training on kyphosis was seen. In conclusion, a 4-months back extensor training program can improve back strength and seems to maintain height and thoracic expansion.

To examine if healthy borderline overweight postmenopausal women with osteoporosis can improve their waist circumference and lipid profile with a moderate physical training program.Randomized controlled trial.One hundred and twelve postmenopausal women were randomized to normal sedentary life or one year of physical training consisting of three brisk walks and 1-2 aerobic exercises/week.Waist circumference reduction, waist circumference reduction in relation to observed level of participation in physical intervention and changes in cholesterol, triglycerides, apolipoproteins B and A1 and high-sensitivity C-reactive protein (hs-CRP).At start the mean (SD) waist circumference was 83.6 (7.7) and 81.8 (7.5) cm in the control and training groups, respectively. In relation to baseline, the 12 months intervention led to a waist reduction of 0.3 cm (2.7) (p=0.36) and 1.6 cm (4.7) (p=0.02) in the respective groups but the inter-group comparison was not significant in an intention-to-treat analysis (p=0.09). The ninety-two women completing the study intervention were analyzed per protocol. A tendency for better waist reduction in relation to the women's observed physical intensity level was observed (p=0.07, ANOVA for linear trend across training intensity levels). Training women improved their waist circumference 1.7 cm (p=0.01) compared to baseline and was borderline significantly better than controls (p=0.059). No significant changes in response to the intervention were observed for blood pressure, cholesterol, triglycerides, apolipoproteins and hs-CRP.A moderate physical exercise program for healthy postmenopausal women during one year reduced the waist circumference in a training intensity dependent manner.

The aim of this study was to investigate whether moderate physical training can improve the bone mineral density (BMD) in women with idiopathic osteoporosis. Ten pre-menopausal women aged 24-44 years diagnosed with idiopathic osteoporosis were included in the study. The physical training program consisted of three fast 30-min walks plus one or two sessions of 1-h training per week during 1 year at a training centre separate from the hospital. All patients were given supplements of vitamin D and calcium. Bone mineral density was measured in the femoral neck area and the lumbar spine by dual energy X-ray absorptiometry. The measurements were performed at baseline and after 12 months of training and compared with the measurements at the time of diagnosis, 1-3 years before the study. Eight women fulfilled the 12-month training period, and their mean (SD) BMD at start was 0.88 (0.08) g/cm(2) in the spine and 0.76 (0.13) g/cm(2) in the femoral neck. The mean spine BMD increase was 0.031 g/cm(2) (3.5%) after 1 year of training, which was significant (Wilcoxon's non-parametric test, p = 0.018). The mean increment in BMD in the femoral neck was insignificant, 0.007 g/cm(2) (0.9%) after the intervention (p = 0.74). However, the bone loss during the 1- to 3-year period from diagnosis to study start was, on average, 0.045 g/cm(2) or 5.0% in the femoral neck (p = 0.042), thus indicating a positive indirect effect of the intervention. There is no evidence-based therapy for women with idiopathic osteoporosis. It is therefore of importance to elucidate the impact of moderate physical activity in this group of patients. A 1-year training program was sufficient to induce a small but significant change in the spine BMD.

In the present study we investigated the functional properties of the three recombinant hyaluronan synthases (HAS proteins) HAS1, HAS2, and HAS3. HAS3-transfected CHO clones exhibited the highest hyaluronan polymerization rate followed by HAS2 transfectants which were more catalytically active than HAS1 transfectants. In living cells all three HAS proteins synthesized hyaluronan chains of high molecular weight (larger than 3.9 x 10(6)). In vitro, the HAS2 isoform produced hyaluronan chains of a molecular weight larger than 3.9 x 10(6), whereas HAS3 produced polydisperse hyaluronan (molecular weight 0.12-1 x 10(6)), and HAS1 synthesized much shorter chains of an average molecular weight of 0.12 x 10(6). Thus, each HAS protein may interact with different cytoplasmic proteins which may influence their catalytic activity. CHO transfectants with the ability to synthesize about 1 microgram hyaluronan/1 x 10 (5) cells/24 h were surrounded by hyaluronan-containing coats, whereas transfectants generating about 4-fold lower amounts of hyaluronan formed coats only in the presence of chondroitin sulfate proteoglycan. An inverse correlation between hyaluronan production on the one hand and cell migration and cell surface CD44 expression on the other was found; a 4-fold lower migration and a 2-fold decrease of cell surface CD44 receptors was seen when hyaluronan production increased 1000-fold over the level in the untransfected cells. The inverse relationships between hyaluronan production and migration and CD44 expression of cells are of importance for the regulation of cell-extracellular matrix interactions.

The purpose of this study was to explore whether mechanical loading by exercise over a 1–year period in postmenopausal women had an effect on the receptor activator for nuclear factor kappa B ligand/osteoprotegerin (RANKL/OPG) system or the levels of the Wnt-signaling antagonist sclerostin. A total of 112 postmenopausal were randomized to either sedentary life (controls) or physical activity (training group). Ninety-two women fulfilled the study protocol. The training program consisted of three fast 30-min walks and one or two 1-h aerobic training sessions per week. The effect on the bone mineral density of the hip assessed with dual X-ray absorptiometry was positive as reported earlier. Blood samples were taken from participants at baseline and after 1 year and serum levels of OPG, RANKL and sclerostin were quantified together with the bone metabolism markers C-terminal telopeptide of collagen type I (CTX) and bone-specific alkaline phosphatase (BALP). The results were analyzed using an analysis of covariance model using baseline values as the covariate. The training group displayed a clear mean increase of OPG +7.55 pg/ml compared to controls (p = 0.007). The mean changes for RANKL +0.19 pg/ml (square-root transformed data) and sclerostin +0.62 pmol/l were non-significant (p = 0.13 and p = 0.34). The changes in bone turnover markers CTX and BALP showed a tendency to decrease in the training group versus controls but the changes were small and non-significant. Although our study is limited in number of participating women, we have been able to show an OPG-associated, and RANKL- and sclerostin-independent, training-induced inhibition of postmenopausal bone loss.

Summary One hundred and twelve postmenopausal women with low bone mineral density (BMD) and forearm fractures were randomized to physical training or control group. After one year the total hip BMD was significantly higher in the women in the physical training group. The results indicate a positive effect of physical training on BMD in postmeno- pausal women with low BMD. Introduction The fivefold increase in hip fracture incidence since 1950 in Sweden may partially be due to an increasingly sedentary lifestyle. Our hypothesis was that physical training can prevent bone loss in postmenopausal women. Methods One hundred and twelve postmenopausal women 45 to 65 years with forearm fractures and T-scores from −1.0 to −3.0 were randomized to either a physical training or control group. Training included three fast 30-minute walks and two sessions of one-hour training per week. Bone mineral density (BMD) was measured in the hip and the lumbar spine at baseline and after one year. Results A per protocol analysis was performed, including 48 subjects in the training group and 44 subjects in the control group. The total hip BMD increased in the training group +0.005 g/cm2 (±0.018), +0.58%, while it decreased −0.003 g/cm2 (±0.019), −0.36%, (p=0.041) in the control group. No significant effects of physical training were seen in the lumbar spine. A sensitivity intention to treat analysis, including all randomized subjects, showed no significant effect of physical training on BMD at any site. Conclusions The results indicate a small but positive effect of physical exercise on hip BMD in postmenopausal women with low BMD.

In the present study we describe a method to prepare membranes with high hyaluronan synthase activity from human glioma cells by pretreatment of the cells with both testicular hyaluronidase and 4-phorbol 12-myristate 13-acetate (PMA). A 23-fold increase in hyaluronan synthase activity was detected in comparison to untreated cells. Using isolated membranes as a source of hyaluronan synthase activity we demonstrate that chain elongation occurs at the reducing end of the hyaluronan molecule. We also present a method to solubilize hyaluronan synthase in active form with 1% digitonin. The solubilized synthase synthesized shorter hyaluronan chains than the membrane bound enzyme. Partial purification of the solubilized enzyme on a Superdex-200 column revealed a 12-fold increase in specific activity. Affinity purified polyclonal antibodies, raised against a synthetic peptide corresponding to the carboxy-terminus of the deduced protein sequence of human hyaluronan synthase recognized a 66 kDa component in the purified preparations. The elution position of the solubilized hyaluronan synthesizing activity immediately after V0 corresponding to a molecular mass of about 600 kDa, suggested that the 66 kDa enzyme forms a complex with other components which may have accessory or regulatory roles during hyaluronan synthesis.