May Measurement Month 2019: an analysis of blood pressure screening results from Spain.

The aim of the May Measurement Month (MMM) is devoted to better understanding the awareness, treatment, and control rates of hypertension in Spain. Presented here are the data corresponding to 2019 campaign. In 2019, a total of 4433 patients (61.5% males) with a mean age of 54.8 years were included. Of all, 96.0% were Caucasian, and 3294 were recruited in pharmacies. The mean values of systolic blood pressure (BP) were 125.6 and of diastolic 76.7 mmHg in the whole population. The most recent previous BP measurement took place more than 1 year before in 27.6% of participants. A total of 1883 were hypertensive (systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg or taking antihypertensive medication), of whom 77.2%/were aware and 71.1% were on medication. Of all, 64.9% of those on medication and 46.1% of all hypertensive participants had a BP controlled to <140/90 mmHg. These data from MMM 2019 continue to indicate the need for an improvement in the awareness, treatment, and control of hypertension in Spain.

Effects of a Combined Therapy With D-002 (Beeswax Alcohols) Plus D-003 (Sugarcane Wax Acids) on Osteoarthritis Symptoms.

Context • Nonsteroidal, anti-inflammatory drugs effectively relieve osteoarthritis (OA) symptoms but also induce adverse effects (AEs) that limit their long-term use, which drives a search for safer treatments. D-002, a mixture of beeswax alcohols, and D-003, a mixture of sugarcane wax acids, have been effective in experimental and clinical studies for patients with OA. Objective • The study intended to investigate the effects on OA symptoms of a combined therapy using D-002 and D-003 (D-002/D-003), which were administered for 6 wk. Design • The study was a randomized, double-blind, placebo-controlled trial. Setting • The study was conducted at the Surgical Medical Research Center in Havana, Cuba. Participants • Participants were patients with mild-to-moderate OA. Intervention • Participants were randomly assigned to 1 of 4 groups-(1) a control group, which received a placebo; (2) the D-002 group (intervention group), which received 50 mg/d of D-002; (3) the D-003 group (intervention group), which received 10 mg/d of D-003; or (4) the D-002/D-003 group (intervention group), which received a combined therapy of 50 mg/d of D-002 plus 10 mg/d of D-003. The control group received tablets that were indistinguishable in appearance from the D-002 and D-003 tablets and had a similar composition, except that the active ingredients were replaced by lactose. The groups took the medications once per day for 6 wk. Outcome Measures • Symptoms were assessed using the Western Ontario and McMaster Individual Osteoarthritis Index (WOMAC) and a visual analogue scale (VAS). The primary outcome was the reduction in the total WOMAC score. The subscale scores on the WOMAC for pain, stiffness, and physical function, the VAS scores, and the use of rescue medications were secondary outcomes. Results • Of the 120 enrolled participants, 116 completed the study. The treatments with D-002, D-003, and D-002/D-003 reduced the mean total WOMAC scores significantly from baseline to postintervention, by 75.1%, 72.8%, and 91.2%, respectively. Compared with the placebo, the treatments decreased the mean WOMAC scores for pain, joint stiffness, and physical function significantly. The VAS scores significantly decreased, showing a 71.4%, a 66.9%, and an 84.7% reduction for the D-002, D-003, and D-002/D-003 groups, respectively. All the reductions were significant from the first week and were enhanced during the trial. The D-002/D-003 treatment was more effective in improving all of the scores than either monotherapy. With respect to rescue medications, 3/30, 2/30, and 2/30 used the medications in the D-002, D-003, and D-002/D-003 groups, respectively, vs 17/30 in the control group. The treatments were well tolerated. Conclusions • Administered for 6 wk, 50 mg/d of D-002 and 10 mg/d of D-003 ameliorated OA symptoms, but the combined therapy, D-002/D-003, was more effective than either monotherapy. All treatments were well tolerated.

Urban environment and health: a cross-sectional multiregional project based on population health surveys in Spain (DAS-EP project) - study protocol.

INTRODUCTION: The European Environment Agency estimates that 75% of the European population lives in cities. Despite the many advantages of city life, the risks and challenges to health arising from urbanisation need to be addressed in order to tackle the growing burden of disease and health inequalities in cities. This study, Urban environment and health: a cross-sectional multiregional project based on population health surveys in Spain (DAS-EP project), aims to investigate the complex association between the urban environmental exposures (UrbEEs) and health. METHODS AND ANALYSIS: DAS-EP is a Spanish multiregional cross-sectional project that combines population health surveys (PHS) and geographical information systems (GIS) allowing to collect rich individual-level data from 17 000 adult citizens participating in the PHS conducted in the autonomous regions of the Basque Country, Andalusia, and the Valencian Community, and the city of Barcelona in the years 2021-2023. This study focuses on the population living in cities or metropolitan areas with more than 100 000 inhabitants. UrbEEs are described by objective estimates at participants' home addresses by GIS, and subjective indicators present in PHS. The health outcomes included in the PHS and selected for this study are self-perceived health (general and mental), prevalence of chronic mental disorders, health-related quality of life, consumption of medication for common mental disorders and sleep quality. We aim to further understand the direct and indirect effects between UrbEEs and health, as well as to estimate the impact at the population level, taking respondents' sociodemographic and socioeconomic characteristics, and lifestyle into consideration. ETHICS AND DISSEMINATION: The study was approved by the regional Research Ethics Committee of the Basque Country (Ethics Committee for Research Involving Medicinal Products in the Basque Country; PI2022138), Andalusia (Biomedical Research Ethics Committee of the Province of Granada; 2078-N-22), Barcelona (CEIC-PSMar; 2022/10667) and the Valencian Community (Ethics Committee for Clinical Research of the Directorate General of Public Health and Center for Advanced Research in Public Health; 20221125/04). The results will be communicated to the general population, health professionals, and institutions through conferences, reports and scientific articles.

Health literacy: association with socioeconomic determinants and the use of health services in Spain.

Background: Health literacy (HL) is the set of social and cognitive skills that determine person's level of motivation and the ability to access, understand and use information to promote and maintain good health. The aim of this study is to assess the level of health literacy, and to analyze its relationship with sociodemographic variables, state of health, and use of health services in the population aged 15 and over in the Valencian Community (Spain). Methods: Cross-sectional study based on a sample of 5,485 subjects participating in the Health Survey of the Valencia Community. The HLS-EU-Q16 was used. As outcome variables we considered HL categorized into 2 levels: Inadequate or Problematic HL and Sufficient HL and the standardized literacy index. Prevalence rates and HL means were estimated and OR were calculated to analyze the association between variables. Results: A total of 12.8% of the subjects surveyed presented an inadequate or problematic degree of HL. This percentage was higher in people >85 years (63.1%), with a low level of education (46.5%), in retired people (27.4%) or in other work situations (25.0%), in foreigners (18.1%), in low-income people (16.2%), with a perception of poor health status (26.9%), chronic disease (18.5%) or with activity limitations (56.4% severe, 19.7% not severe). Significant differences were found. With the exception of chronic disease, all the variables analyzed were associated with HL. Low HL was associated with a lower consumption of medicines, a greater use of health services, general medical consultations, poorer knowledge of new health technologies and fewer preventive health visits. Conclusion: The percentage of inadequate or problematic HL was globally not very high, but certain population subgroups notably presented a high degree of inadequate or problematic HL. Raising the HL level of such groups should be regarded as a priority. HL was shown to be associated with the service use and new health technology use. Enhancing the population's HL should lead to the following: a greater probability of adopting preventive practices; improving the use of the health system; and boosting people's abilities to manage and to improve their own health.

[May Measurement Month 2019: Screening Analysis In Spanish Community Pharmacies and Detection of Masked Hypertension]. / Campaña de medida de la presión arterial ('May Measurement Month') 2019: análisis del cribado en farmacias comunitarias españolas y detección de hipertensión enmascarada.

Aim: To know within the scope of the May Measurement Month (MMM) project, the blood pressure (BP) situation in the Spanish population, disseminate the importance of its periodic measurement and estimate the prevalence of masked hypertension (MH). Methods: Transversal descriptive study in Spanish community pharmacies during May 2019. Variables: Systolic blood pressure (SBP), diastolic blood pressure (DBP) in millimetres of mercury (mmHg), heart rate (HR) in beats per minute (bpm).Subjects with BP ≥130/85 and <149/90 were offered the possibility of home blood pressure monitor- ing (HBPM) to confirm MH. Results: A total of 3402 valid records performed by 491 pharmacists. In all 61.9% women, mean age 56.6 years. A total of 143 (4.2%) had never measured BP and 918 (27.0%) had not measured BP in the last year; 1047 were taking anti-hypertensives, of whom 45.7% had high BP.A total of 780 (22.9%) subjects had high BP values; both, 252 (7.4%). mSBP and mDBP was 125.0 mmHg and 76.5 mmHg, respectively; higher in men (P<0.001). mHR was 72.6 bpm..A direct relationship was detected between SBP and DBP and BMI (P<0.0001). mSBP and mHR were higher in smokers (P<0.0001). In diabetic patients, SBP, DBP and HR were greater.A total of 61 subjects with suspected MH agreed to undergo HBPM. A total of 25 (40.1%) resulted in BP ≥135/85 mmHg. Conclusions: Almost a quarter of subjects had BP ≥140/90 mmHg. The risk factors most closely related to high BP were overweight, diabetes and age; 40% of suspected cases of MH were confirmed by means of HBPM.

Mapping the awareness of inequalities in health programs in Spanish communities: moving forward together.

The aim of this study is to map the awareness of gender, socioeconomic, immigrant and ethnic health inequalities in health at schools, maternal health and traffic injury health prevention programs. The study was conducted in the 19 health descentralized areas in Spain, 17 autonomous community (ACs) and the 2 autonomous cities (ACities). The data were collected from May 2008 to January 2009. The unit of analysis was the collection of policy documents setting out the programs mentioned above and the related support material in each AC. A reading guide was used to analyze the awareness of inequalities. With regard to health at schools, 2 of 10 programs show a high awareness of inequalities and include many specific proposals to be implemented at the local level. Regarding maternal health, 13 ACs have prepared support material with high awareness of inequalities to be implemented. A traffic injury program has been created in two ACs. We map the whole situation in Spain regarding the health programs that we have used as examples and their awareness of inequalities. We can conclude that there are differences between the regions studied in Spain and in general, the awareness of inequalities is low.

Caesarean section rates in immigrant and native women in Spain: the importance of geographical origin and type of hospital for delivery.

BACKGROUND: Spain has become a principal destination for immigrants and delivery is the major reason for hospitalization in this population. However, research about inequities between native and immigrant women regarding the quality of the care received during pregnancy and delivery is still scarce. One of the indicators used to evaluate the quality of the obstetric care is the rate of caesarean sections (CSs). METHODS: A cross-sectional study of 215 379 single deliveries from Spanish and immigrant women from Latin America, East Europe and Maghreb was carried out in Spain in 2005-06. Prevalence of CS according to maternal and neonatal characteristics was calculated by geographical origin. Two associations were explored by means of multiple logistic regression analysis. First, the association between geographical origin and the risk of CS in public or private hospitals separately, and, second, the risk of CS for women from the same geographical origin depending on whether they delivered at public or private hospitals. RESULTS: Overall, the risk of CS was lower for immigrants as a whole than for native women (odds ratio (OR) = 0.83 95% confidence interval (CI) = 0.80-0.85), but the risk varied markedly by area of origin, being higher for Latin Americans (OR = 1.09 95% CI = 1.05-1.13) and lower for East Europeans (OR = 0.61 95% CI = 0.57-0.66) and Maghrebians (OR = 0.60 95% CI =0.57-0.63). Public hospitals followed the overall pattern of risk. CS risk was higher in private than in public hospitals for all groups. However, the increase in risk was higher for immigrant than for natives. CONCLUSION: Immigrants in Spain are a heterogeneous population regarding the risk of CS. Geographical origin and type of hospital are key aspects underlying such a risk.

[Health literacy: psychometric behaviour of the HLS-EU-Q16 questionnaire]. / Alfabetización en salud: propiedades psicométricas del cuestionario HLS-EU-Q16.

OBJECTIVE: To describe the psychometric properties and the level of understanding of the health literacy questionnaire HLS-EU-Q16 in Spanish, implemented in the Health Survey of the Valencian Region (Spain) of 2016. METHOD: Descriptive cross-sectional study to describe understanding, reliability, structure and internal consistency of the questionnaire on a sample of 5485 subjects, aged 15 or over, who participated in the survey. RESULTS: The percentages of understanding without much difficulty were high. Reliability was high (intraclass correlation coefficient:.923; kappa:.814). The factorial analysis suggested a unifactorial structure (79.1% of variability explained by the common factor), with high factorial loads. The consistency was high (Cronbach's alpha: 0.982). CONCLUSIONS: The HLS-EU-Q16 in Spanish is a short, adequate and valid instrument to measure the level of health literacy in the population.

Antioxidant effects of D-004, a lipid extract from the Roystonea regia fruit, on the plasma of healthy men.

The aim of this study was to conduct a randomized, double-blind and placebo-controlled study to investigate the effects of D-004, a lipid extract of the Roystonea regia fruit that prevents testosterone- and phenylepinephrine-induced prostate hyperplasia in rodents, on plasma oxidative markers in healthy men. We enrolled male volunteers (20-55 years) in good health and without lower urinary tract symptoms. Thirty-four eligible participants were randomized to placebo or D-004 (320 mg) capsules administered daily for 6 weeks. An interim check-up and a final visit were conducted after 3 and 6 weeks of therapy, respectively. Physical examinations were performed at each visit, and laboratory tests were performed at baseline and at treatment completion. Oxidative variables included plasma malondialdehyde (MDA), total hydroxyperoxides (TOH), sulphydryl (SH) groups and total antioxidant status (TAS). We assessed treatment compliance and addressed adverse experiences (AEs) at weeks 3 and 6. At week 6, with D-004, the mean reductions of plasma MDA (26.7%), TOH (18.8%) and SH groups (31.6%), and the mean increase of TAS (35.3%) were significantly different from those of placebo (P<0.001 for plasma TAS, P<0.0001 for all other comparisons). D-004 did not differ from the placebo in safety indicators. There were two withdrawals (both in the D-004 group), with one due to dyspepsia (the only AE during the trial). In conclusion, D-004 displayed antioxidant effects on plasma oxidative markers in healthy men, which was consistent with findings from laboratory experimental studies.

Ex vivo antioxidant effects of D-004, a lipid extract from Roystonea regia fruits, on rat prostate tissue.

AIM: To investigate whether oral treatment with D-004, a lipid extract of the Cuban royal palm fruit, produces antioxidant effects in the prostate tissue of normal and testosterone (T)-treated rats. METHODS: In our first experiment, normal rats were distributed into five groups: one group treated with the vehicle and four groups treated with D-004 (100, 200, 400 or 800 mg/kg). In our second experiment, rats were randomized into five groups: a negative control group and four T-injected groups. The latter were comprised of a positive control group treated with the vehicle, and three groups treated with D-004 (200, 400 or 800 mg/kg). RESULTS: In normal rats, D-004 (100-800 mg/kg) inhibited significantly and dose-dependently iron-initiated malondialdehyde (MDA) accumulation in prostate homogenates (35.7%-80.0%) vs the controls. D-004 (200-800 mg/kg) significantly reduced baseline MDA and carbonyl groups in prostate homogenates of normal rats to approximately 80% and 50%, respectively, and totally (100%) in T-treated rats. CONCLUSION: Oral treatment with D-004 reduced MDA and carbonyl groups dose-dependently and markedly in normal and T-injected rats. These findings show that D-004 given at doses effective to prevent prostate hyperplasia also produces antioxidant effects in the prostate tissue.

Effects of D-004, a lipid extract of the fruit of the Cuban royal palm (Roystonea regia) or the lipidosterolic extract of saw palmetto (Serenoa repens) on the sexual activity in male rats: A controlled, experimental study.

BACKGROUND: The etiology of benign prostatic hyperplasia (BPH) is not completely understood, but hormonal changes in aging men seem to be pivotal. Dihydrotestosterone, a potent, active metabolite of testosterone, is formed by the enzymatic action of prostate 5α-reductase and causes cell growth and hyperplasia. Consistent with this action, male sexual dysfunction has been clinically documented to be among the drug-related adverse events associated with 5α-reductase inhibitors. The lipidosterolic extract of saw palmetto (LESP) fruit (Serenoa repens) has been used to treat BPH. D-004, a lipid extract of Roystonea regia Royal palm fruit, has been found to prevent prostatic hyperplasia induced by testoste-rone in rodents and to competitively inhibit prostate 5α-reductase activity in vitro. OBJECTIVE: The purpose of this study was to assess the effects of D-004 and LESP, administered as single or repeated doses, on the sexual activity in male rats. METHODS: This controlled, experimental study was conducted at the Pharmacology Department, Centre of Natural Products, National Centre for Scientific Research, Havana City, Cuba. Adult male Wistar rats weighing 250 to 300 g were randomized into 5 groups: 2 groups treated orally with D-004 (400 and 800 mg/kg); 2 groups treated orally with LESP (400 and 800 mg/kg); and 1 control group orally administered a water vehicle. Sexual activity behavior (the number of mounts and intromissions, mount latency, and intromission latency) was assessed during 2 observation periods: 90 minutes after the initial dose and at the end of the 30-day treatment. Latency was defined as time elapsed between the first mount and intromission. RESULTS: A total of 50 rats (mean [SD] age, 10 [3] weeks; mean [SD] weight, 295 [10] g) were included in the experiment. There were no significant difterences in the mean number of mounts, intromissions, mount latency, or intromission latency in the groups treated with single or repeated doses of D-004 or LESP (400 and 800 mg/kg) compared with the controls. There was also no between-group difterence in mating behavior among the active treatment groups. All rats survived up to study completion, with normal behavior (weight gain, food intake, daily observations, without any sign of toxicity). There were no observable adverse events during the study. CONCLUSIONS: D-004 and LESP administered as a single dose or repeated doses for 30 days did not significantly affect male rat sexual activity behavior compared with a vehicle control group.

Contribution of the Economic Crisis to the Risk Increase of Poor Mental Health in a Region of Spain.

Previous research suggests that the economic crisis can affect mental health. The purpose of this study was to analyse the association of risk of poor mental health with various socioeconomic, demographic, health, quality of life, and social support variables; and to evaluate the contribution of socioeconomic variables most affected by the beginning of the economic crisis (employment situation and income) on the changes in the prevalence of the risk of poor mental health between 2005 and 2010. A study of prevalence evolution in adult population residents of the Valencian Community in the Spanish Mediterranean was conducted. We studied 5781 subjects in 2005 and 3479 in 2010. Logistic regression models have been adjusted to analyse the association between variables. A standardisation procedure was carried out to evaluate which part of the changes in overall prevalence could be attributed to variations in the population structure by age, sex, employment status, and income between the years under study. The prevalence of GHQ+ increased from 2005 to 2010, in both men and women. Several variables were closely associated with the risk of poor mental health (sex, age, country of birth, number of nonmental chronic diseases, social support, disability, cohabitation in couple, employment status, and income). The changes produced as a result of the onset of the economic crisis in income and unemployment (increase in low income and in unemployment rates) contributed to the increase of poor mental health risk. This could confirm the sensitivity of mental health to the economic deterioration caused by the crisis.

D-003 does not possess oestrogenic potential in-vivo: findings of the uterotrophic assay.

D-003 is a mixture of long-chain fatty acids purified from sugarcane wax that inhibits both cholesterol synthesis prior to mevalonate formation, and lipid peroxidation. D-003 has been shown to prevent bone loss and bone resorption in ovariectomized rats, and significantly improves bone resorption markers in postmenopausal women with reduced bone mineral density. As hormone-replacement therapy, D-003 displays cholesterol-lowering and anti-resorptive effects. We have studied its potential oestrogenic activity in-vivo using the uterotrophic assay. Rats were randomly distributed into five groups: a sham-operated group and four groups of ovariectomized rats, one treated with vehicle, one with D-003 (50 mg kg(-1)), one with oestradiol benzoate (30 microg kg(-1)) and one with D-003 (50 mg kg(-1)) plus oestradiol benzoate (30 microg kg(-1)). Treatments were administered for 14 days. Ovariectomy decreased the values of relative uterus weight, epithelium cell height and endometrial thickness compared with sham-operated rats, and these effects were all significantly reduced with oestradiol benzoate, but not with D-003. Concurrent administration of D-003 and oestradiol benzoate had statistically similar effects on all variables as oestradiol benzoate alone. In conclusions, D-003 orally given at 50 mg kg(-1), a dose that prevents bone loss and bone resorption in ovariectomized rats, did not display oestrogenic/anti-oestrogenic activity in-vivo, as assessed in the uterotrophic assay.

Effects of coconut oil on testosterone-induced prostatic hyperplasia in Sprague-Dawley rats.

Benign prostatic hyperplasia (BPH) is the benign uncontrolled growth of the prostate gland, leading to difficulty with urination. Saw palmetto lipid extracts (SPLE), used to treat BPH, have been shown to inhibit prostate 5a-reductase, and some major components, such as lauric, myristic and oleic acids also inhibit this enzyme. Coconut oil (CO) is also rich in fatty acids, mainly lauric and myristic acids. We investigated whether CO prevents testosterone-induced prostate hyperplasia (PH) in Sprague-Dawley rats. Animals were distributed into seven groups (10 rats each). A negative control group were injected with soya oil; six groups were injected with testosterone (3 mg kg(-1)) to induce PH: a positive control group, and five groups treated orally with SPLE (400 mg kg(-1)), CO or sunflower oil (SO) (400 and 800 mg kg(-1)). Treatments were given for 14 days. Rats were weighed before treatment and weekly thereafter. Rats were then killed and the prostates were removed and weighed. CO (400 and 800 mg kg(-1)), SPLE (400 mg kg(-1)) and SO at 800 mg kg(-1), but not at 400 mg kg(-1), significantly reduced the increase in prostate weight (PW) and PW:body weight (BW) ratio induced by testosterone (% inhibition 61.5%, 82.0%, 43.8% and 28.2%, respectively). Since CO and SPLE, but not SO, contain appreciable concentrations of lauric and myristic acids, these results could be attributed to this fact. In conclusion, this study shows that CO reduced the increase of both PW and PW:BW ratio, markers of testosterone-induced PH in rats.

Protective effect of policosanol on endothelium and intimal thickness induced by forceps in rabbits.

Policosanol is a cholesterol-lowering drug isolated from sugar cane wax with concomitant antiplatelet effects that prevents lipofundin-induced atherosclerotic lesions in rabbits and rats, including foam cell formation, and also reduces foam cell formation in carrageenan-induced granulomas in rats, while it inhibits proliferation of smooth muscle cells induced in rabbit cuffed artery. This study was undertaken to determine whether policosanol prevents endothelium damage and increase in arterial wall thickness in rabbits with arterial walls damaged with a forceps. Artery forceps were placed over the central artery of the right ear of all rabbits, and each artery was injured eight times. Animals were randomly distributed into four groups: a positive control group treated with Tween 20/H2O vehicle, two groups treated with policosanol (5 and 25 mg/kg, respectively), and a group treated with aspirin (8 mg/kg). Treatments were given for 30 days. Damaged arteries were examined by light and electron (transmission and scanning) microscopy. To evaluate intimal thickening, areas of intima were measured, and a significant reduction in policosanol-treated animals was observed. The endothelial surface, studied with scanning electron microscopy, revealed several types of damage. In control group, the endothelial surface was severely damaged. De-endothelialized areas were reduced in policosanol-treated animals. Platelet adhesion to subendothelium was seen in all animals of the control group, whereas policosanol-treated groups exhibited significantly reduced platelet adhesion. Policosanol also reduced, dose-dependently, the platelet sequestration induced in the damaged vessel wall, partially preventing the reduction in platelet count. It is concluded that policosanol prevents endothelium injury and reduces significantly intimal thickness of rabbit arteries damaged with forceps.

Preventive effect of D-002, a mixture of long-chain alcohols from beeswax, on the liver damage induced with CCl4 in rats.

D-002 is a mixture of higher aliphatic primary alcohols purified from beeswax with antioxidant effects. Acute hepatotoxicity induced with CCl4 in rats has been related to increased hepatic lipid peroxidation and prevented with some antioxidants. This study investigated whether D-002 could prevent the acute CCl4-induced hepatotoxicity in rats. Animals were randomly distributed into four groups: a negative control treated orally with the vehicle and three groups injected with CCl4 (1 mL/kg) and treated orally either with the vehicle (positive control) or with D-002 (25 and 100 mg/kg). Eighteen hours after CCl4 dosing, rats were anesthetized, and livers were removed for histopathological studies. Some portions were taken and homogenized for assessing malondialdehyde (MDA) concentrations. Positive, but not negative, controls showed ballooned cells, swollen hepatocytes, and lipid-included hepatocytes, as well as necrotic areas and inflammatory infiltrates. D-002 (25 and 100 mg/kg) dose-dependently and significantly (P < .01) decreased the frequency of all abnormal liver cell types and increased that of normal hepatocytes compared with the positive controls, not showing necrotic areas or inflammatory infiltrates. D-002 dose-dependently decreased hepatic MDA levels, but only in the highest dose group were these levels significantly lower than in the positive control. In conclusion, D-002 effectively prevented the histological liver disturbances and lowered MDA levels, a marker of cellular lipid peroxidation, in rats treated with CCl4. Since increased liver lipid peroxidation has been postulated as a cause of CCl4-induced liver damage in rats, the preventive effects of D-002 could be due to its antioxidant action, but such a proposal still requires further research.

Comparison of the efficacy and tolerability of chondroitin plus glucosamine and D-002 (beeswax alcohols) in subjects with osteoarthritis symptoms.

BACKGROUND/AIMS: Osteoarthritis (OA), the commonest joint disorder, is a leading cause of disability. Symptomatic slow-acting drugs for OA (SYSADOA), particularly glucosamine plus chondroitin sulphate (GS/CS), are effective for symptom relief, protect joint cartilage and delay OA progression, with a good safety profile. D-002, a mixture of beeswax alcohols that inhibits both cyclooxygenase and 5-lipoxygenase activities, has been effective in experimental and clinical OA studies, showing also a chondroprotective effect. OBJECTIVES: To compare the effects of D-002 and GS/SC administered for 12 weeks on OA symptoms. METHODS: Participants were randomized to GS/CS (375/300 mg) or 50 mg D-002 once daily for 12 weeks. Symptoms were assessed by the Western Ontario and McMaster Individual Osteoarthritis Index (WOMAC) and the Visual Analogy Scale (VAS) scores. The primary outcome was the reduction of the total WOMAC score. Secondary outcomes included WOMAC pain, stiffness and function scores, VAS score and rescue medication consumption. RESULTS: Of 60 randomized patients, 59 completed the study. D-002 and GS/SC reduced significantly total WOMAC score (72.1% and 78.5%, respectively), and pain, joint stiffness and physical function scores versus baseline. VAS scores decreased significantly with D-002 (76.6%) and GS/SC (76.8%). The reductions, significant from the second week, were enhanced over the trial. Rescue medications were consumed by 3/30 D-002 and 4/30 GS/SC patients. No differences between groups were found. Treatments were well tolerated. CONCLUSIONS: D-002 (50 mg/day) administered for 12 weeks was safe and comparable to GS/SC for alleviating OA symptoms (pain, stiffness, and functional limitation) (RPCEC00000180).

Plasma levels, tissue distribution, and excretion of radioactivity after single-dose administration of ((3)H)-oleic acid added to D-004, a lipid extract of the fruit of Roystonea regia, in rats.

BACKGROUND: D-004, a lipid extract of the fruit of Roystonea regia, contains a mixture of fatty acids-mainly oleic, lauric, palmitic, and myristic acids, with oleic acid being among the most abundant-that has been found to reduce the risk for prostatic hyperplasia (PH) induced with testosterone (T) in rats. The pharmacokinetic profile of D-004 has not been reported. OBJECTIVE: The objective of this study in rats was to assess plasma levels, tissue distribution, and excretion of total radioactivity (TR) after single-dose administration of oral D-004 radiolabeled with ((3)H)-oleic acid, as a surrogate for the pharmacokinetics of D-004. METHODS: This experimental study was conducted at the Pharmacology Department, Center of Natural Products, National Center for Scientific Research, Havana, Cuba. Single doses of suspensions of ((3)H)-oleic acid 0.16 µCi/mg mixed with D-004 400 mg/kg (radioactive dose/animal 7.2 µCi) were given orally to male Wistar rats weighing 150 to 200 g assigned to the treated or control group. Three rats were euthanized at each of the following times: 0.25, 0.5, 1, 1.5, 2, 4, 8, 24, 48, 72, 96, and 144 hours after study drug administration. After administration, the rats euthanized at the last experimental time point were housed individually in metabolism cages. Urine and feces samples were collected daily. At each time point, blood samples were drawn and plasma samples were obtained using centrifugation. After euthanization, tissue samples (liver, lungs, spleen, brain, kidneys, adipose tissue, muscle, stomach, small and large intestines, adrenal glands, heart, testes, prostate, and seminal vesicles) were quickly removed, washed, blotted, and homogenized. Plasma (100 µL), tissue aliquots (100 mg), feces (10 mg), and urine (100µL) were dissolved and TR was measured. Samples were assayed in duplicate. Results were expressed in µgEq of radio-labeled oleic acid per milliliter of plasma or urine or gram of tissue or feces. Plasma, tissue, feces, and urine samples of rats that did not receive ((3)H)-oleic acid were used as controls. Excretion was expressed as the percentage of the radioactivity excreted via each route with respect to the total radioactive dose administered to each rat. RESULTS: A total of 50 rats were included in the experiment (mean age, 4 weeks; mean weight, 310 g). Absorption was rapid; mean Cmax was 195.56 (31.12) µgEq/mL, and mean Tmax was 2 hours. Thereafter, a biphasic decay of TR was found: a rapid first phase (t1/2α, 1.33 hours), followed by a slower second elimination phase (t1/2ß, 36.07 hours). Radioactivity was rapidly and broadly distributed throughout the tissues, with more accumulating in the prostate than elsewhere. In the first 8 hours, accumulation of TR was greatest in the prostate, followed by the liver, small intestine, and plasma. Subsequently, TR increased in the small intestine, while it decreased in the liver and plasma. In contrast, over the periods of 24 and 144 hours after administration, TR increased in the adipose tissue, while it decreased in the other tissues and plasma. During those intervals, TR was greatest in the prostate, followed by adipose tissue. Mean peak radioactivity in the prostate (562.41 µgEq/g) was reached at 4 hours and decreased slowly thereafter. The prostate had the highest values of t1/2ß and cumulative AUC compared with the other tissues and plasma. Mean (SD) TR was similar in feces (33.48% [4.90%]) and urine (28.96% [5.32%]), with total excretion being 62.40% (5.90%) of the administered dose. CONCLUSIONS: In this experimental study, after single-dose administration of oral D-004 radiolabeled with ((3)H)-oleic acid in rats, TR was rapidly and widely distributed across the tissues, with the prostate having the highest accumulation of radioactivity. Excretion of TR was limited, with similar amounts being excreted in feces and urine. The broad distribution of radiolabeled oleic acid and/or its metabolites suggests (SD) pharmacokinetic rationale for the effectiveness of D-004 in reducing the risk for PH induced with T in rats.

Effects of combination treatment with policosanol and omega-3 fatty acids on platelet aggregation: A randomized, double-blind clinical study.

BACKGROUND: Policosanol is a mixture of long-chain primary aliphatic alcoholspurified from sugar cane wax that has cholesterol lowering and antiplatelet effects. Omega-3 fatty acids (FA) have triglyceride lowering and antiplatelet effects. Combination treatment with policosanol and omega-3 FA (Ω23FA) has been associated with significant inhibition of platelet aggregation in rabbits compared with either drug alone. OBJECTIVE: The aim of this study was to investigate the effects of combination treatment with Ω3FA (1 g/d) and policosanol (Ω3FA+Poli) compared with Ω3FA (1 g/d) plus placebo (Ω3FA+Pla) on platelet aggregation in human patients with hypercholesterolemia. METHODS: This randomized, double-blind, clinical study at the Surgical Medical Research Center (Havana City, Cuba) recruited outpatients from lipid clinics, with some atherosclerotic risk factors. Outpatients of both sexes aged 20 to 75 years with serum total cholesterol (TC) levels ≥5 and <6 mmol/L were eligible to enroll. They were included in the study at the end of a 4-week diet stabilization period if their platelet aggregation to arachidonic acid (AA) was ≥50% and serum TC level remained ≥5 mmol/L. Patients were then evenly randomized to receive Ω3FA (1 g/d) + placebo or Ω3FA (1 g/d) + policosanol (10 mg/d) to be taken PO with the evening meal for 21 days. Treatment was assigned according to a randomization code using balanced blocks and a 1:1 allocation ratio. Inhibition of platelet aggregation to AA was the primary efficacy variable, while effects on platelet aggregation to collagen and epinephrine and on lipid profile were secondary variables. Drug compliance and adverse events (AEs) were monitored. Tolerability was assessed using physical examinations and laboratory test results. RESULTS: Sixty-four subjects were initially enrolled. Fifty-four patients (30 women, 24 men; mean [SD] age, 58.4 [12] years, [range, 40-70 years]) met the inclusion criteria and were randomized to treatment; 2 groups of 27. After 21 days, platelet aggregation to AA was significantly inhibited in the 2 groups. Ω3FA+Poli inhibited platelet aggregation to all agonists by ≥20%. Platelet aggregation to AA 1.0 and 1.5 mM was inhibited with combination treatment (39.6% and 33.9%, respectively; both P < 0.001 vs baseline; P < 0.001 and P < 0.01, respectively, vs Ω3FA+Pla) and with Ω3FA+Pla (11.0% and 13.3%; both, P < 0.001). Combination treatment was more effective in inhibiting platelet aggregation to AA 1.0 and 1.5 mM in 28.6% (P < 0.001) and 20.6% (P < 0.01), respectively. Platelet aggregation to collagen 1 µg/mL was significantly inhibited with combination treatment and with Ω3FA+Pla compared with baseline (43.2% and 15.1%, respectively; both, P < 0.001), but the effects of combination treatment were significantly greater (P < 0.01). Platelet aggregation to epinephrine 0.1 mM was inhibited with Ω3FA+Poli and Ω3FA+Pla (34.8% and 20.1%; both, P < 0.001), with similar results for both groups. Bleeding time did not change significantly for either group and Ω3FA+Pla did not significantly change the lipid profile. Combination treatment did significantly reduce levels of low-density lipoprotein cholesterol (LDL-C) (17.4%; P < 0.001 vs baseline, P < 0.05 vs Ω3FA+Pla) and TC (10.1%; P < 0.001 vs baseline, P < 0.05 vs Ω3FA+Pla), increase high-density lipoprotein cholesterol (HDL-C) levels (18.0%; P < 0.001 vs baseline), but did not significantly change triglyceride levels. Three patients (2 from the Ω3FA+Poli group and 1 from the Ω3FA+Pla group) withdrew from the trial, though none were due to AEs. Two patients receiving combination treatment reported mild AEs (headache). All treatments were well tolerated. CONCLUSIONS: In these patients, policosanol (10 mg/d) administered concomitantly with Ω3FA (1 g/d) enhanced the inhibition of platelet aggregation to AA and collagen, but not to epinephrine, compared with Ω3FA+Pla, without significantly affecting bleeding time. Concomitant treatment was also associated with reduced levels of LDL-C and TC and raised HDL-C levels. All treatments were well tolerated.