Habitual intake of advanced glycation endproducts is not associated with worse insulin sensitivity, worse beta cell function, or presence of prediabetes or type 2 diabetes: The Maastricht Study.

BACKGROUND & AIMS: A diet high in advanced glycation endproducts (AGEs) is a potential risk factor for insulin resistance, beta cell dysfunction, and ultimately type 2 diabetes. We investigated associations between habitual intake of dietary AGEs and glucose metabolism in a population-based setting. METHODS: In 6275 participants of The Maastricht Study (mean ± SD age: 60 ± 9, 15.1% prediabetes and 23.2% type 2 diabetes), we estimated habitual intake of dietary AGEs Nε-(carboxymethyl)lysine (CML), Nε-(1-carboxyethyl)lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) by combining a validated food frequency questionnaire (FFQ) with our mass-spectrometry dietary AGE database. We determined insulin sensitivity (Matsuda- and HOMA-IR index), beta cell function (C-peptidogenic index, glucose sensitivity, potentiation factor, and rate sensitivity), glucose metabolism status, fasting glucose, HbA1c, post-OGTT glucose, and OGTT glucose incremental area under the curve. Cross-sectional associations between habitual AGE intake and these outcomes were investigated using a combination of multiple linear regression and multinomial logistic regression adjusting for several potential confounders (demographic, cardiovascular, and lifestyle factors). RESULTS: Generally, higher habitual intake of AGEs was not associated with worse indices of glucose metabolism, nor with increased presence of prediabetes or type 2 diabetes. Higher dietary MG-H1 was associated with better beta cell glucose sensitivity. CONCLUSIONS: The present study does not support an association of dietary AGEs with impaired glucose metabolism. Whether higher intake of dietary AGEs translates to increased incidence of prediabetes or type 2 diabetes on the long term should be investigated in large prospective cohort studies.

Pyridoxamine reduces methylglyoxal and markers of glycation and endothelial dysfunction, but does not improve insulin sensitivity or vascular function in abdominally obese individuals: A randomized double-blind placebo-controlled trial.

AIM: To investigate the effects of pyridoxamine (PM), a B6 vitamer and dicarbonyl scavenger, on glycation and a large panel of metabolic and vascular measurements in a randomized double-blind placebo-controlled trial in abdominally obese individuals. MATERIALS AND METHODS: Individuals (54% female; mean age 50 years; mean body mass index 32 kg/m2 ) were randomized to an 8-week intervention with either placebo (n = 36), 25 mg PM (n = 36) or 200 mg PM (n = 36). We assessed insulin sensitivity, ß-cell function, insulin-mediated microvascular recruitment, skin microvascular function, flow-mediated dilation, and plasma inflammation and endothelial function markers. PM metabolites, dicarbonyls and advanced glycation endproducts (AGEs) were measured using ultra-performance liquid chromatography tandem mass spectrometry. Treatment effects were evaluated by one-way ANCOVA. RESULTS: In the high PM dose group, we found a reduction of plasma methylglyoxal (MGO) and protein-bound Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1), as compared to placebo. We found a reduction of the endothelial dysfunction marker soluble vascular cell adhesion molecule-1 (sVCAM-1) in the low and high PM dose group and of soluble intercellular adhesion molecule-1 (sICAM-1) in the high PM dose, as compared to placebo. We found no treatment effects on insulin sensitivity, vascular function or other functional outcome measurements. CONCLUSIONS: This study shows that PM is metabolically active and reduces MGO, AGEs, sVCAM-1 and sICAM-1, but does not affect insulin sensitivity and vascular function in abdominally obese individuals. The reduction in adhesion markers is promising because these are important in the pathogenesis of endothelial damage and atherosclerosis.

Could the region you live in prevent or precipitate kidney stone formation due to mineral intake through tap water? An analysis of nine distribution regions in Flanders.

OBJECTIVES: To analyse the mineral content of tap water in Flanders and assess if the region one lives in could prevent or precipitate stone formation due to a difference in mineral content. METHODS: Data from six water companies providing tap water to nine regions in Flanders regarding calcium, magnesium, potassium, sodium and sulphate content in tap water was retrieved. Minimum and maximum values were collected and compared between the different geographical regions. RESULTS: The highest calcium level was found in region 9 with a value of 157.0 mg/L, which is almost 10 times the value found in region 8 (16.1 mg/L). Region 6 had the highest magnesium (31.8 mg/L), potassium (30.5 mg/L), sodium (126.6 mg/L) and sulphate (218.5 mg/L) levels. The lowest level of magnesium (2.7 mg/L) was found in region 1, which was almost 12 times lower as in Region 6. Region 9 had the lowest level of potassium (1.5 mg/L), which is a factor 20 lower than Region 6. The lowest sodium and sulphate levels were found in region 8 (6.8 mg/L and 3.0 mg/L), respectively. The difference between the highest and lowest level of sulphate was a factor 70. CONCLUSION: There is a broad range in the minerals found in tap water between the different production sites in the nine distribution regions in Flanders. However, due to the high standards tap water has to meet in Flanders, the region one lives in will not lead to a higher or lower risk of kidney stone formation if the advised 2 to 3 L per day are consumed.

How Reliable Is Endoscopic Stone Recognition? A Comparison Between Visual Stone Identification and Formal Stone Analysis.

Objective: To assess the diagnostic accuracy and intra-observer agreement of endoscopic stone recognition (ESR) compared with formal stone analysis. Introduction: Stone analysis is a corner stone in the prevention of stone recurrence. Although X-ray diffraction (XRD) and infrared spectroscopy are the recommended techniques for reliable formal stone analysis, this is not always possible, and the process takes time and is costly. ESR could be an alternative, as it would give immediate information on stone composition. Materials and Methods: Fifteen endourologists predicted stone composition based on 100 videos from ureterorenoscopy. Diagnostic accuracy was evaluated by comparing the prediction from visual assessment with stone analysis by XRD. After 30 days, the videos were reviewed again in a random order to assess intra-observer agreement. Results: The median diagnostic accuracy for calcium oxalate monohydrate was 54% in questionnaire 1 (Q1) and 59% in questionnaire 2 (Q2), whereas calcium oxalate dihydrate had a median diagnostic accuracy of 75% in Q1 and 50% in Q2. The diagnostic accuracy for calcium hydroxyphosphate was 10% in Q1 and 13% in Q2. The median diagnostic accuracy for calcium hydrogen phosphate dihydrate and calcium magnesium phosphate was 0% in both questionnaires. The median diagnostic accuracy for magnesium ammonium phosphate was 20% in Q1 and 40% in Q2. The median diagnostic accuracy for uric acid was 22% in both questionnaires. Finally, there was a diagnostic accuracy of 60% in Q1 and 80% in Q2 for cystine. The intra-observer agreement ranged between 45% and 72%. Conclusion: Diagnostic accuracy of ESR is limited and intra-observer agreement is below the threshold of acceptable agreement.

A 4-Week Diet Low or High in Advanced Glycation Endproducts Has Limited Impact on Gut Microbial Composition in Abdominally Obese Individuals: The deAGEing Trial.

Dietary advanced glycation endproducts (AGEs), abundantly present in Westernized diets, are linked to negative health outcomes, but their impact on the gut microbiota has not yet been well investigated in humans. We investigated the effects of a 4-week isocaloric and macronutrient-matched diet low or high in AGEs on the gut microbial composition of 70 abdominally obese individuals in a double-blind parallel-design randomized controlled trial (NCT03866343). Additionally, we investigated the cross-sectional associations between the habitual intake of dietary dicarbonyls, reactive precursors to AGEs, and the gut microbial composition, as assessed by 16S rRNA amplicon-based sequencing. Despite a marked percentage difference in AGE intake, we observed no differences in microbial richness and the general community structure. Only the Anaerostipes spp. had a relative abundance >0.5% and showed differential abundance (0.5 versus 1.11%; p = 0.028, after low- or high-AGE diet, respectively). While the habitual intake of dicarbonyls was not associated with microbial richness or a general community structure, the intake of 3-deoxyglucosone was especially associated with an abundance of several genera. Thus, a 4-week diet low or high in AGEs has a limited impact on the gut microbial composition of abdominally obese humans, paralleling its previously observed limited biological consequences. The effects of dietary dicarbonyls on the gut microbiota composition deserve further investigation.

Habitual intake of dietary advanced glycation end products is not associated with generalized microvascular function-the Maastricht Study.

BACKGROUND: Endogenously formed advanced glycation end products (AGEs) may be important drivers of microvascular dysfunction and the microvascular complications of diabetes. AGEs are also formed in food products, especially during preparation methods involving dry heat. OBJECTIVES: We aimed to assess cross-sectional associations between dietary AGE intake and generalized microvascular function in a population-based cohort. METHODS: In 3144 participants of the Maastricht Study (mean ± SD age: 60 ± 8 y, 51% men) the dietary AGEs Nε-(carboxymethyl)lysine (CML), Nε-(1-carboxyethyl)lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were estimated using the combination of our ultra-performance LC-tandem MS dietary AGE database and an FFQ. Microvascular function was determined in the retina as flicker light-induced arteriolar and venular dilation and as central retinal arteriolar and venular equivalents, in plasma as a z score of endothelial dysfunction biomarkers (soluble vascular adhesion molecule 1 and soluble intracellular adhesion molecule 1, soluble E-selectin, and von Willebrand factor), in skin as the heat-induced skin hyperemic response, and in urine as 24-h albuminuria. Associations were evaluated using multiple linear regression adjusting for demographic, cardiovascular, lifestyle, and dietary factors. RESULTS: Overall, intakes of CML, CEL, and MG-H1 were not associated with the microvascular outcomes. Although higher intake of CEL was associated with higher flicker light-induced venular dilation (ß percentage change over baseline: 0.14; 95% CI: 0.02, 0.26) and lower plasma biomarker z score (ß: -0.04 SD; 95% CI: -0.08, -0.00 SD), the effect sizes were small and their biological relevance can be questioned. CONCLUSIONS: We did not show any strong association between habitual intake of dietary AGEs and generalized microvascular function. The contribution of dietary AGEs to generalized microvascular function should be further assessed in randomized controlled trials using specifically designed dietary interventions.

Global Variations in the Mineral Content of Bottled Still and Sparkling Water and a Description of the Possible Impact on Nephrological and Urological Diseases.

Kidney stone disease (KSD) is a complex disease. Besides the high risk of recurrence, its association with systemic disorders contributes to the burden of disease. Sufficient water intake is crucial for prevention of KSD, however, the mineral content of water might influence stone formation, bone health and cardiovascular (CVD) risk. This study aims to analyse the variations in mineral content of bottled drinking water worldwide to evaluate the differences and describes the possible impact on nephrological and urological diseases. The information regarding mineral composition (mg/L) on calcium, bicarbonate, magnesium, sodium and sulphates was read from the ingredients label on water bottles by visiting the supermarket or consulting the online shop. The bottled waters in two main supermarkets in 21 countries were included. The evaluation shows that on a global level the mineral composition of bottled drinkable water varies enormously. Median bicarbonate levels varied by factors of 12.6 and 57.3 for still and sparkling water, respectively. Median calcium levels varied by factors of 18.7 and 7.4 for still and sparkling water, respectively. As the mineral content of bottled drinking water varies enormously worldwide and mineral intake through water might influence stone formation, bone health and CVD risk, urologists and nephrologists should counsel their patients on an individual level regarding water intake.

Variations in the mineral content of bottled 'carbonated or sparkling' water across Europe: a comparison of 126 brands across 10 countries.

INTRODUCTION: Kidney stone disease is a common disease with high recurrence rates. Sufficient intake of water is the cornerstone in primary prevention of stone disease. However, the mineral composition of water can affect urinary minerals and influence stone formation. The aim of this study is to assess the variation in the mineral composition of bottled sparkling or carbonated drinking water across Europe. MATERIAL AND METHODS: The two largest supermarket chains in each participating country were visited to obtain data on mineral composition regarding bicarbonate, calcium, magnesium, potassium, sodium and sulphates of sparkling or carbonated waters by reading the ingredient labels on the bottles supplied by the manufacturers. Alternatively, the web-shops of these supermarkets were consulted. RESULTS: In total, 126 sparkling water brands across ten European countries were analysed regarding mineral composition. The median concentrations per mineral varied greatly. The greatest variation in median mineral content was found for sodium and sulphates with levels ranging from 3.1 mg/l to 63.0 mg/l and 6.0 mg/l to 263.0 mg/l respectively. A wide distribution of calcium content was found in Switzerland, with calcium levels reaching up to 581.6 mg/l. CONCLUSIONS: This study confirms that the mineral composition of sparkling or carbonated water varies greatly across Europe. Patients with kidney stone disease should be aware that the mineral content of water may influence stone formation and be mindful of the great variation that exists between different water brands. Mineral water can be a source of potential promotors or inhibitors of stone formation and patients and urologists need to be mindful of this.

Variations in the Mineral Content of Bottled "Still" Water Across Europe: Comparison of 182 Brands Across 10 Countries.

Introduction: Kidney stone disease (KSD) is a highly prevalent disease worldwide. As water intake and its mineral content influence stone formation and recurrence, patients and physicians must be aware of the mineral content of drinkable water. We analyzed commercial bottled still water within Europe to assess the variation in its mineral composition across different manufacturers and countries. Materials and Methods: Data on the mineral composition of bottled still water regarding bicarbonate, calcium, magnesium, potassium, sodium, and sulfate concentration (mg/L) were collected from ten European countries. To collect the data, the two main supermarket chains in each participating country were either visited to check for the ingredient label on bottles or the online shop was consulted through the website of the supermarket in question. Descriptive statistics such as simple boxplots were used to illustrate the variation in mineral content. Results: One hundred eighty-two different commercial water brands were analyzed. Up to a fivefold variation in average concentrations per mineral between countries was observed. For calcium, a wide distribution was found in France and Switzerland compared with other countries with calcium levels ranging from 10.5 to 565 mg/L and 8.4 to 579 mg/L, respectively. By consuming 2 L of water with such high calcium levels, the daily reference intake for calcium is already achieved. Conclusions: The mineral content of bottled still water across Europe varies greatly. For patients with KSD it is important to be aware of the mineral content of the water they drink, as it might influence stone recurrence rates and necessitate alterations of their diet.

The Floating Acromion: A Rare and Previously Unreported Injury Possibly Requiring Surgical Stabilization.

Acromion fractures are increasingly seen as a postoperative complication following reversed shoulder arthroplasty. However, traumatic fractures of the acromion, usually caused by direct trauma, are rare. Therefore, the current literature lacks standardized clinical guidelines regarding the surgical treatment of these kinds of fractures. We present a traumatic acromion fracture and concomitant distal clavicle fracture, resulting in a so-called "floating acromion." A fifty-four-year-old female patient was presented at the Emergency Department following a fall from the stairs. She complained of severe pain in the left shoulder. Radiographic evaluation of the left shoulder revealed an acromion fracture and concomitant distal clavicle fracture. Initially, since there was no dislocation, this "floating acromion" was treated conservatively. However, after 4 weeks, no improvement in pain was seen and a control CT scan revealed no callus formation. Considering the possibility that this could be a biomechanically unstable injury, together with the persistent severe pain, it was decided to proceed with surgical treatment. A lateral clavicle plate was used to stabilize the acromion fracture. Postoperatively, the patient was provided with a sling. She was regularly seen at the outpatient clinic. After two weeks of circumduction exercises, she was allowed to build up active movement under the supervision of a shoulder physiotherapist. Nevertheless, she developed a frozen shoulder. However, our patient fully recovered with complete restoration of shoulder function. Therefore, for operative management of acromion fractures, we suggest the use of a lateral clavicle plate which fits remarkably well on the lateral spine and acromion.

Improved quantification of muscle insulin sensitivity using oral glucose tolerance test data: the MISI Calculator.

The Muscle Insulin Sensitivity Index (MISI) has been developed to estimate muscle-specific insulin sensitivity based on oral glucose tolerance test (OGTT) data. To date, the score has been implemented with considerable variation in literature and initial positive evaluations were not reproduced in subsequent studies. In this study, we investigate the computation of MISI on oral OGTT data with differing sampling schedules and aim to standardise and improve its calculation. Seven time point OGTT data for 2631 individuals from the Maastricht Study and seven time point OGTT data combined with a hyperinsulinemic-euglycaemic clamp for 71 individuals from the PRESERVE Study were used to evaluate the performance of MISI. MISI was computed on subsets of OGTT data representing four and five time point sampling schedules to determine minimal requirements for accurate computation of the score. A modified MISI computed on cubic splines of the measured data, resulting in improved identification of glucose peak and nadir, was compared with the original method yielding an increased correlation (ρ = 0.576) with the clamp measurement of peripheral insulin sensitivity as compared to the original method (ρ = 0.513). Finally, a standalone MISI calculator was developed allowing for a standardised method of calculation using both the original and improved methods.

Benefits of flooding-induced aquatic adventitious roots depend on the duration of submergence: linking plant performance to root functioning.

Background and Aims: Temporal flooding is a common environmental stress for terrestrial plants. Aquatic adventitious roots (aquatic roots) are commonly formed in flooding-tolerant plant species and are generally assumed to be beneficial for plant growth by supporting water and nutrient uptake during partial flooding. However, the actual contribution of these roots to plant performance under flooding has hardly been quantified. As the investment into aquatic root development in terms of carbohydrates may be costly, these costs may - depending on the specific environmental conditions - offset the beneficial effects of aquatic roots. This study tested the hypothesis that the balance between potential costs and benefits depends on the duration of flooding, as the benefits are expected to outweigh the costs in long-term but not in short-term flooding. Methods: The contribution of aquatic roots to plant performance was tested in Solanum dulcamara during 1-4 weeks of partial submergence and by experimentally manipulating root production. Nutrient uptake by aquatic roots, transpiration and photosynthesis were measured in plants differing in aquatic root development to assess the specific function of these roots. Key Results: As predicted, flooded plants benefited from the presence of aquatic roots. The results showed that this was probably due to the contribution of roots to resource uptake. However, these beneficial effects were only present in long-term but not in short-term flooding. This relationship could be explained by the correlation between nutrient uptake and the flooding duration-dependent size of the aquatic root system. Conclusions: The results indicate that aquatic root formation is likely to be selected for in habitats characterized by long-term flooding. This study also revealed only limited costs associated with adventitious root formation, which may explain the maintenance of the ability to produce aquatic roots in habitats characterized by very rare or short flooding events.

Cinnamaldehyde, Carvacrol and Organic Acids Affect Gene Expression of Selected Oxidative Stress and Inflammation Markers in IPEC-J2 Cells Exposed to Salmonella typhimurium.

Essential oils and organic acids are used as feed additives to improve health status and reduce colonization with pathogens. Although bactericidal in vitro, concentrations achieved in the animal gut are probably not lethal to pathogens. The aim of this study was to investigate the effects of cinnamaldehyde, carvacrol and cinnamic, lactic and propionic acids on the ability of Salmonella typhimurium ATCC 14028 (ST) to invade intestinal epithelial cells (IPEC-J2) and on the expression levels of immune related genes in the cells. The minimum inhibitory concentration (MIC) and non-inhibitory concentration (NIC) were determined and influence on the invasion capacity of ST was investigated. The structure of fimbriae and flagella was analysed by electron microscopy, and expression levels of HSP70, IkBa, IL-8 and IL-10 in the IPEC-J2 cells were carried out by q-PCR. Cinnamaldehyde, carvacrol and cinnamic and propionic acids inhibited ST invasion but not cell viability, bacterial viability and motility or the development of flagella. Propionic acid and cinnamaldehyde in combination with cinnamic acid caused structural impairment of fimbriae. Cinnamaldehyde up-regulated expression of HSP70 irrespective of the presence of organic acids or ST; exposure to carvacrol induced HSP70 only in the presence of propionic acid and ST. © 2016 The Authors. Phytotherapy Research published by John Wiley & Sons Ltd.

Addressing patient health care demands in systemic sclerosis: pre-post assessment of a psycho-educational group programme.

OBJECTIVES: Patients diagnosed with systemic sclerosis (SSc) report a high need for education and support. To address these needs, a short, group-based psycho-educational programme for patients with SSc was developed and evaluated. METHODS: A pre-post test design was utilised. Participants completed questionnaires on physical and psychological functioning. Furthermore, patients were asked to evaluate the content of the programme by questionnaire. RESULTS: Data from 41 patients were available for analysis. Patients reported less helplessness after the intervention, and higher acceptance of their limitations. However, no difference in depressed mood and physical functioning was observed. Patients reported high satisfaction with the content of the programme. CONCLUSIONS: Despite the limited changes in psychological and physical functioning, this psycho-educational programme addresses patients' needs reported in previous study and therefore contributes to the improvement of care for patients with SSc.

Work-related health complaints in surgical residents and the influence of social support and job-related autonomy.

OBJECTIVES: The aim of this cross-sectional study was to investigate the influence of job-related autonomy and social support provided by consultants and colleagues on the stress-related health complaints of surgical residents in the Netherlands. METHODS: All (n = 400) Dutch residents in training in general surgery were sent validated self-report questionnaires. Odds ratios were calculated predicting health and exposure to long-term stress for gender, number of working hours, type of hospital, level of social support, job-related autonomy and training phase. The interactions between job-related autonomy and level of social support provided by consultants and colleagues, and all variables, were analysed. RESULTS: A total of 254 of 400 (64%) residents returned questionnaires that were eligible for analysis. Residents experienced more health complaints than the average member of the Dutch working population (4.0 versus 2.5; p = 0.000). Male and senior residents were significantly 'healthier' than female and junior residents, respectively. Social support by consultants was a strong predictor of health and social support by colleagues showed a significant interaction with gender. Women and residents in university hospitals experienced less social support by consultants than men and residents in general teaching hospitals. Residents working in university hospitals experienced lower levels of job-related autonomy and less support from colleagues in comparison with those working in general teaching hospitals. A working week of > 60 hours adversely affected health and job-related autonomy. CONCLUSIONS: Social support provided by consultants and colleagues, and job control, are important factors that interact with the work-associated, stress-related health of residents in training in general surgery. Residents report a greater number of health complaints than the average member of the working population, especially female and junior residents. General teaching hospitals seem to provide better support at work than university hospitals.

Randomized clinical trial comparing blunt tapered and standard needles in closing abdominal fascia.

Glove perforation frequently occurs during the course of surgical procedures, introducing risks for both surgeons and patients. The aim of this study was to compare the use of blunt tapered and "sharp" needles during abdominal wall closure with respect to the incidence of glove perforation and the convenience of needle handling. A series of 200 patients undergoing laparotomy in a 6-month period for general surgical disorders were randomized to two groups; in one, the abdominal fascia was closed with a blunt tapered needle; in the other, a sharp needle was used. The main outcome measures were glove perforation and convenience of handling the needle. Univariate and multivariate analyses were performed. In all, 56 glove perforations occurred during 40 (20%) surgical procedures. Perforation rates differed significantly: 12% for the blunt (n = 100) tapered needle and 28% (n = 100) for the sharp needle (p = 0.003). Only in 12 cases (21%) was the glove perforation detected at surgery. The type of needle (odds ratio 0.35, p = 0.006) and time taken to close the fascia (odds ratio 1.001, p = 0.05) significantly affected the risk of glove perforation. At multivariate logistic regression analysis the type of needle (odds ratio 0.23, p = 0.004) and the visual analog linear scale (VAS) for ease of needle handling (odds ratio 1.18, p = 0.019) were important predictive factors for glove perforation. With the blunt tapered needle, the VAS was significantly (p = 0.0003) higher at primary laparotomy than at relaparotomy. Use of the blunt tapered needle reduces the incidence of glove perforation. Laborious closure predicts glove perforation. Blunt tapered needles are less convenient in closing a scarred abdominal fascia.

Raloxifene reduces procarboxypeptidase U, an antifibrinolytic marker. A 2-year randomized, placebo-controlled study in healthy early postmenopausal women.

OBJECTIVE: The aim of this study was to compare the long-term effects of two dosages of raloxifene with oral hormone therapy (HT; conjugated equine estrogens combined with medroxyprogesterone acetate) on procarboxypeptidase U. DESIGN: In a randomized, double-blind, placebo-controlled, 2-year study, 95 healthy, nonhysterectomized, early postmenopausal women received either daily raloxifene 60 mg (n = 24), raloxifene 150 mg (n = 23), HT (conjugated equine estrogens 0.625 mg + medroxyprogesterone acetate 2.5 mg, n = 24), or placebo (n = 24). At baseline and after 6, 12, and 24 months, fasting plasma procarboxypeptidase U concentrations were measured. RESULTS: Six months of treatment with raloxifene 60 mg and raloxifene 150 mg were associated with significant decreases in plasma procarboxypeptidase U concentrations, which were sustained after 12 and 24 months. Raloxifene 60 mg: t = 0, 619 +/- 89 U/L (mean +/- SD); t = 6, 574 +/- 87 U/L; t = 12, 571 +/- 96 U/L; t = 24, 568 +/- 92 U/L; ANCOVA versus placebo, P = 0.026. Raloxifene 150 mg: t = 0, 608 +/- 67 U/L; t = 6, 580 +/- 73 U/L; t = 12, 578 +/- 70 U/L; t = 24, 562 +/- 61 U/L; ANCOVA versus placebo, P = 0.039. No significant changes were found in the HT group. CONCLUSION: Long-term treatment with raloxifene reduced procarboxypeptidase U plasma concentrations.

Raloxifene treatment increases plasma levels of beta-endorphin in postmenopausal women: a randomized, placebo-controlled study.

OBJECTIVE: To evaluate the effect of the selective estrogen receptor modulator raloxifene hydrochloride (Evista, Eli Lilly and Company, Indianapolis, IN) on plasma levels of beta-endorphin, and to determine whether beta-endorphin levels and menopausal symptoms are related. DESIGN: A randomized, double-blind, placebo-controlled pilot study. SETTING: Endocrinology outpatient department. PATIENT(S): Forty postmenopausal women. INTERVENTION(S): The women received raloxifene, 60 mg/d, or placebo for 3 months. A questionnaire on climacteric symptoms was administered before and after treatment. MAIN OUTCOME MEASURE(S): Circulating levels of beta-endorphin, climacteric symptom score, and correlation with beta-endorphin levels. RESULT(S): Raloxifene treatment significantly increased levels of beta-endorphin and did not significantly affect climacteric symptoms, with the exception of worsening vasomotor symptoms. No significant relation was seen between plasma levels of beta-endorphin and climacteric symptoms. CONCLUSION(S): Raloxifene modulates plasma levels of beta-endorphin without concomitantly relieving climacteric symptoms, as seen with hormone replacement therapy.

Neither long-term treatment with raloxifene nor hormone replacement therapy modulate cardiac function in healthy postmenopausal women: two randomized, placebo-controlled, 2-year studies.

OBJECTIVE: Our purpose was to investigate the long-term effects of raloxifene, compared with opposed and unopposed estrogen replacement therapy, on echocardiographic parameters of left ventricular systolic function in healthy postmenopausal women. A total of 157 women were studied in 2 randomized, double-blind, placebo-controlled, 2-year studies. STUDY DESIGN: In study I, 60 postmenopausal women who had undergone hysterectomy received daily raloxifene, 60 mg (n = 15); raloxifene, 150 mg (n = 15); conjugated equine estrogens (CEE), 0.625 mg (n = 15); or placebo (n = 15). In study II, 97 postmenopausal women who had not undergone hysterectomy received daily raloxifene, 60 mg (n = 24); raloxifene, 150 mg (n = 24); CEE, 0.625 mg, plus medroxyprogesterone acetate (MPA), 2.5 mg (n = 24); or placebo (n = 25). M-mode, quantitative 2-dimensional and Doppler echocardiographic measurements were performed at baseline and after 1 and 2 years. RESULTS: Neither after 1 year nor after 2 years of treatment were echocardiographic parameters found to differ from baseline in both raloxifene groups, as well as in the unopposed CEE and the CEE/MPA groups, compared with the placebo group. CONCLUSION: Within 2 years of raloxifene treatment, no effect on echocardiographic parameters of left ventricular systolic function was found. Unopposed CEE or CEE/MPA also showed no effect.