A new Acanthotetilla sponge from the Southwest Atlantic (Tetillidae, Spirophorina, Tetractinellida, Demospongiae), with an updated discussion on the diversity, distribution and morphologic characters of Acanthotetilla spp.

Acanthotetilla is a genus of tetillid sponges diagnosed by the presence of medium-sized, heavily spined oxeas, which are known as megacanthoxeas (or simply acanthoxeas). Currently, seven species are known worldwide: three from the Western Atlantic (A. gorgonosclera, A. rocasensis and A. walteri), three from the Western Indian (A. hemisphaerica, A. enigmatica and A. seychellensis) and one from the Western Pacific (A. celebensis). A megacanthoxea-bearing specimen was obtained from the Fernando de Noronha Archipelago, Southwest Atlantic, in 2016. It is described here as a new Acanthotetilla, namely, A. noronhensis sp. nov. This new species has two categories of megacanthoxeas, like A. celebensis from Celebes/Sulawesi Sea, Indonesia. However, the former differs from the latter, as well as from other congeners, by the combination of endolithic habit and spiculation. Acanthotetilla noronhensis sp. nov. is known on the basis of a single specimen from a large collection of sponges from Fernando de Noronha. Besides, the species was not found in other sponge collections from different areas of Brazil, including oceanic areas. Thus, the new species has probably a low abundance and restricted distribution, alike all other known Acanthotetilla species, aside A. celebensis, which (regardless its low abundance) occurs in a large sector of the western Pacific. Despite A. noronhensis sp. nov. and A. celebensis being separated by a wide geographic distance, the unique occurrence of two categories of megacanthoxeas might suggest closer phylogenetic relationship and biogeographic history as well. A wider discussion on the diversity, distribution and morphologic characters of Acanthotetilla spp. is supplied in this study. A comparative taxonomic table and a taxonomic identification key to Acanthotetilla spp. is supplied as well.

Checklist, diversity descriptors and selected descriptions of a highly diverse intertidal sponge (Porifera) assemblage at Costa do Descobrimento (Bahia, Brazil).

Costa do Descobrimento is located in southern Bahia, Brazil, and only 22 species of sponges (Porifera) were known from the area until now, despite its important reef formations. In the present study, we report a checklist of the sponges of Costa do Descobrimento and their distribution in the studied reefs, with several species illustrated in life. We also describe nine new sponge records for this region, some of which are new records for Brazil, or new records of species previously only poorly known. We present alpha and beta diversity indices and compare the sponge assemblage of the sampled locations. Four reefs were considered: two fringing reefs (Arraial D'Ajuda-AA and Coroa Vermelha / Mutá-CVM) and two offshore Municipal Marine Park "Parque Municipal Marinho- (P.M.M. Coroa Alta-CA and P.M.M. Recife de Fora-RF). A total of 229 specimens were collected (224 Demospongiae, 2 Homoscleromorpha and 3 Calcarea). These were classified in 101 morphotypes. Studied materials included representatives of 15 orders, 34 families and 48 genera. The richest orders are Haplosclerida (29 spp.), Poecilosclerida (15 spp.) and Tetractinellida (11 spp.). The richest families were Chalinidae (24 spp.), Clionaidae (7 spp.) and Mycalidae and Suberitidae (6 spp. each). The richest genus is, by far, Haliclona (20 spp.). Only 13 species were shared among all four reefs surveyed, namely Amphimedon viridis, Cinachyrella alloclada, C. apion, Cladocroce caelum, Cliona varians, Dysidea robusta, Mycale (Naviculina) diversisigmata, Niphates erecta, Spirastrella hartmani, Tedania (Tedania) ignis, Terpios fugax, Tethya bitylastra and T. maza. The reefs with the highest richness were CA and CVM, and the lowest richness was observed in RF. The most similar reefs in terms of species composition were CA and CVM, while AA and RF were more dissimilar to the previous reefs, but also from each other. While the difference among CA, CVM and AA was mainly explained by species turnover, RF differed from the previous based on its lower richness (nestedness component). Even though CA and CVM were the richest reefs, AA presented the highest number of exclusive species, highlighting the uniqueness of this reef, and urging the inclusion of local beachrock fringing reefs in a more holistic conservation strategy at Costa do Descobrimento.

Microbiome diversity from sponges biogeographically distributed between South America and Antarctica.

Sponges from South America and Antarctica are evolutionarily closely related. Specific symbiont signatures that could differentiate these two geographic regions are unknown. This study aimed to investigate the microbiome diversity of sponges from South America and Antarctica. In total 71 sponge specimens were analyzed (Antarctica: N = 59, 13 different species; South America: N = 12, 6 different species). Illumina 16S rRNA sequences were generated (2.88 million sequences; 40K ± 29K/sample). The most abundant symbionts were heterotrophic (94.8 %) and belonged mainly to Proteobacteria and Bacteroidota. EC94 was the most abundant symbiont and dominated the microbiome of some species (70-87 %), comprising at least 10 phylogroups. Each of the EC94 phylogroups was specific to one genus or species of sponge. Furthermore, South America sponges had higher abundance of photosynthetic microorganisms (2.3 %) and sponges from Antarctica, the highest abundance of chemosynthetic (5.5 %). Sponge symbionts may contribute to the function of their hosts. The unique features from each of these two regions (e.g., light, temperature, and nutrients) possibly stimulate distinct microbiome diversity from sponges biogeographically distributed across continents.

Three new Hymedesmia Bowerbank, 1864 (Demospongiae, Poecilosclerida, Hymedesmiidae) from the Southeast Pacific (Peru and Chile).

Despite its 2000 km long shoreline, to date less than 50 sponge species have been reported from the entire Peruvian coast. A large collecting effort targeting marine sponges was undertaken between 2007 and 2009, yielding a comprehensive collection of nearly 900 samples, whose taxonomic study is underway. Three new species of Hymedesmiidae are presently described from the Peruvian coast, all belonging in Hymedesmia (Hymedesmia), one of which also found in Chile. Hymedesmia (H.) santarositae sp. nov., from Isla Santa Rosa (Paracas), is characterized by the presence of microstrongyles next to sigmas. Hymedesmia (H.) peruana sp. nov., from Isla Foca (Piura), is diagnosed by its three categories of acanthostyles, and single categories of tornotes and arcuate isochelae. Hymedesmia (H.) humboldti sp. nov., from Moquega and Arequipa regions in Peru, and Antofagasta and Atacama regions in Chile, is diagnosed by its two categories of acanthostyles, and single categories of (aniso)strongyles and arcuate isochelae, the latter abundant at the surface. An identification key for Hymedesmia spp. from the South-eastern Pacific, South-western Atlantic, the Sub-Antarctic and the Antarctic is provided.

New species of Crella (Pytheas) Topsent, 1890 and Crellomima Rezvoi, 1925 (Crellidae, Poecilosclerida, Demospongiae) from Chilean shallow and Argentinean deep waters, with a synthesis on the known phylogenetic relationships of crellid sponges.

Here, we describe four new species of Crellidae Dendy, 1922 and discuss characters and relationships from published molecular phylogenies including crellid sponges. New species proposed are Crella (Pytheas) chiloensis Fernandez, Gastaldi, Pardo Hajdu, sp. nov., from southern Chile (15 m depth), C. (P.) desventuradae Fernandez, Gastaldi, Zapata-Herndez Hajdu, sp. nov., from Desventuradas Archipelago (1020 m depth), Crella (P.) santacruzae Fernandez, Gastaldi, Thompson Hajdu, sp. nov., from deep waters off Argentina (750 m depth) and Crellomima sigmatifera Fernandez, Gastaldi Hajdu, sp. nov., from the Chilean fjords region (ca. 20 m depth). These new species are set apart from each other and from known species mainly due to aspects of their spiculation. Chelae microscleres and acanthostyles supply characters that might be used to infer phylogenetic relationships and to verify the monophyly of Crella Gray, 1867 and Crellidae, which has seemingly been contradicted by preliminary molecular data available in the systematics literature. Our own interpretation of phylogenetic affinities, in the light of morphological characters from previous taxonomic studies, argues for a classification reassessment of materials (vouchers) included in these molecular phylogenies, especially in the case of Crella incrustans (Carter, 1885). We argue that currently available molecular phylogenetic outcomes for crellid sponges are not supportive of the polyphyly of Crella and Crellidae.

An update on the diversity of marine sponges in the southern gulf of Mexico coral reefs.

Until now, 127 species of marine sponges have been recorded in the southern Gulf of Mexico (SGoM). In this study, we describe the sponge fauna recorded on 16 coral reefs of the SGoM, defined as the Mexican waters of the Gulf of Mexico (GoM), during a period from 2005 to 2019. We report 80 sponge species, including 34 first geographic records for the southern GoM region. The latter are fully described and illustrated, taking into account 24 that represent new records for the GoM: Agelas conifera, Agelas sventres, Agelas wiedenmayeri, Prosuberites carriebowensis, Desmanthus meandroides, Cliona aprica, Cliona dioryssa, Placospongia ruetzleri, Haliclona (Gellius) megasclera, Haliclona (Reniera) aff. portroyalensis, Neopetrosia proxima, Xestospongia arenosa, Calyx podatypa, Shiphonodictyon xamaycaense, Acarnus innominatus, Iotrochota arenosa, Polymastia tenax, Svenzea cristinae, Svenzea flava, Svenzea tubulosa, Svenzea zeai, Timea stenosclera, Stellettinopsis megastylifera, Suberea flavolivescens. The present work highlights the understimated and remarkable diversity of reef-associated sponges within the Campeche Bank Coral reef systems. Present work data was compiled with existing published information to produce an updated list of 161 known sponges in the southern GoM.

Sponges from Doumer Island, Antarctic Peninsula, with description of new species of Clathria (Axosuberites) Topsent, 1893 and Hymeniacidon Bowerbank, 1858, and a re-description of H. torquata Topsent, 1916.

Antarctic sponges were mainly studied from trawling or dredging (shallow and deep water) during pioneering oceanographic expeditions carried out since the late 19th century. More recently, sponge collections by SCUBA diving have allowed the detection of species in more cryptic habitats such as rocky walls. In this study, we analyzed Antarctic sponges collected by SCUBA (in 2016 to 2018; shallower than 25 m) around Doumer Island (Palmer Archipelago, Western Antarctic Peninsula-WAP), where only five sponge species have been known. We gathered over 215 specimens, most part identified; 18 known species and one new species. Clathria (Axosuberites) retamalesi sp. nov., is set apart from its congeners on account of the combination of its habit, categories and dimensions of spicules. The East Antarctic material named as Hymeniacidon spec. (3397 m depth) from the Gauss scientific collection has been related to the shallow species H. torquata Topsent, 1916. We described H. torquata based in several specimens (n= 51) from Doumer Island (WAP), only ca. 41 km from Petermann Island (the type locality). Spicules of H. torquata are smaller than the ones present in the Hymeniacidon spec. material, which is here named Hymeniacidon hentscheli sp. nov., since it does not fit into any known cold water species of Hymeniacidon from Antarctica or the Southern Hemisphere, due to a combination of habit, oscula shape, and spicule dimensions. Only five sponge species were previously known from Doumer Island, also collected by SCUBA. Our findings suggest that the ongoing study of collections of sponges assembled at Doumer Island will still yield new taxonomic findings.

Efficacy and tolerability of Roystonea regia lipid extract (D-004) and terazosin in men with symptomatic benign prostatic hyperplasia: a 6-month study.

BACKGROUND: Benign prostatic hyperplasia (BPH), a common urological disease in aging men, frequently produces lower urinary tract symptoms (LUTS). Clinical studies have shown that terazosin relaxes the smooth muscle of the prostate and bladder, facilitates bladder emptying, improves LUTS, increases maximum urinary flow, and reduces the residual volume of urine. D-004, a lipid extract of the fruit of the Cuban royal palm (Roystonea regia), presents a similar efficacy to Saw palmetto. Clinical studies have demonstrated its efficacy and safety in short- and medium-term trials in patients with BPH. The objective of this study was to compare the efficacy and tolerability of D-004 with terazosin for 6 months on LUTS in patients with BPH. METHODS: The present phase III study had an open, randomized, comparative design, with two parallel groups who received D-004 (320 mg/day) or terazosin (5 mg/day) for 6 months. The study included men at least 50 years of age, with evidence of the LUTS of moderate intensity according to the International Symptoms of the Prostate (IPSS). The effects on the IPSS Scale was the primary efficacy variable. The effects on the size of the prostate and the residual volume were secondary variables. The subjective self-perception of symptom relief at trial completion was a collateral outcome. Analysis was done by intention-to-treat. RESULTS: The study included 100 men with a diagnosis of BPH, confirmed by digital rectal examination and ultrasonography, and moderate LUTS (IPSS score >7, <19). Baseline characteristics were similar in both groups. Nine patients did not continue the study: one from group D-004 (due to protocol violation) and eight from the terazosin group (six due to adverse events and two due to protocol violation; p < 0.01). D-004 and terazosin significantly reduced the IPSS scores at the end of the 6 months of therapy by 74.2% and 66.1%, respectively, with respect to baseline values. Comparisons between groups performed showed that, at the end of the treatment, D-004 was more effective (p < 0.05) than terazosin in reducing the IPSS score. Although the average size of the prostate was reduced in both groups, this reduction reached statistical significance only for D-004. On the other hand, postvoid residual volume was significantly and similarly reduced in both groups. Both treatments were safe, while D-004 was better tolerated than terazosin. CONCLUSIONS: D-004 administered at a dose of 320 mg/day for 6 months showed comparable efficacy with terazosin (5 mg/day) in reducing the LUTS (IPSS score), producing a significant decrease in prostate volume and postvoid residual volume. Both treatments were safe, with better tolerability for D-004 as compared with terazosin.

Taxonomy of deep-water tetillid sponges (Porifera, Demospongiae, Spirophorina) from Brazil, with description of three new species and new characters.

Since the 19th century the deep-sea sponges from Brazil have been studied and many of them are still being discovered. This study describes five species of tetillid sponges from deep waters of the Brazilian economic exclusive zone; three are new, one is a new occurrence, and another is a known species which is here analyzed. The new species found are: Cinachyrella clavaeformis sp. nov. from the Columbia Seamount (85 m depth), Cinachyrella strongylophora sp. nov. from the Almirante Saldanha Seamount (270 m depth) and Craniella curviclada sp. nov. from slope of the Espírito Santo Basin (500 m depth). The two new species of Cinachyrella possess microacanthoxeas like those found in Cinachyrella kuekenthali (Uliczka 1929); this last species occurs in Caribbean region (4-100 m depth) and in N, NE and SE Brazil (0.2-100 m depth). The type material of Craniella corticata (Boury-Esnault 1973); from NE Brazil (75 m depth), has been found to be a synonym of Cinachyrella kuekenthali. Craniella crustocorticata van Soest 2017; from the Guyana shelf and slope (618-500 m depth), is here reported from the slope of NE and SW Brazil (400-700 m depth). A disorganized choanosomal skeleton (in Cinachyrella clavaeformis sp. nov.), strongyles (in Cinachyrella strongylophora sp. nov.) and a single-layered cortex of tangential oxeas (in Craniella crustocorticata) are new diagnostic characters that have led us to propose slight amendments in the definitions of Cinachyrella Wilson 1925 and Craniella Schmidt 1870. We discuss these and other morphological characters as well as their usefulness in Tetillidae. The diversity, distribution and bathymetry of tetillid sponges from Brazil are discussed and our knowledge of the composition of deep-sea sponges (deeper than 100 m) off Brazil is updated.

Cinachyrella anatriaenilla sp. nov., a new tetillid sponge with microacanthoxeas from American Samoa in the South Pacific.

Several sponges from American Samoa, collected by the Coral Reef Research Foundation, Republic of Palau, were tentatively identified by one of us as Acanthotetilla cf seychellensis (Thomas 1973), due to the possession of relatively small acanthose oxeas, compared to those of other species of the genus Acanthotetilla Burton 1959. These sponges were later compared to Cinachyrella australiensis (Carter 1886), taking into account the lack of conspicuous spination on the acanthose oxeas and general features of spiculation and skeletal organisation. The specimens were later considered to represent a new species of the genus Cinachyrella Wilson 1925, after a careful comparison was made between the American Samoan specimens and C. australiensis which also contains small acanthose oxeas. Several recent molecular phylogenetic studies have confirmed the generic assignment of one of the American Samoan specimens as belonging to Cinachyrella. Cinachyrella anatriaenilla sp. nov., described herein, is the fifth of 40 Cinachyrella spp. that contain lightly spined microacanthoxeas.

Lissodendoryx (Ectyodoryx) Lundbeck, 1909 (Coelosphaeridae, Poecilosclerida, Demospongiae) from Southern Chile: new species and a discussion of morphologic characters in the subgenus.

Our ongoing studies of the Chilean sponge fauna revealed four new species of Lissodendoryx (Ectyodoryx) that are described here, including three from the fjord's region (< 30 m depth, L.(E.) ballena sp. nov., L. (E.) corrugata sp. nov.,      L. (E.) coloanensis sp. nov.), and one from the deep waters off Diego Ramírez Archipelago (ca. 2000 m, L. (E.) diegoramirezensis sp. nov.). In addition, the type of L. (E.) anacantha was revised and found to bear much larger acanthostyles than originally reported. Our results revealed skeletal architectures quite distinct from that reported from the type species of L. (Ectyodoryx), and not predicted in the current diagnosis of Lissodendoryx, requiring an amended diagnosis. Ectosomal megascleres also set the majority of the new species apart from the type species of L. (Ectyodoryx), which does not have terminally microspined (sub)tylotes. This character is widespread in Lissodendoryx and might be pointing to phylogenetic affinities across the current subgeneric arrangement. Further morphologic characters and alternative phylogenetic scenarios are discussed, including hymedesmiid and myxillid affinities of the species described here.

Phylogeny of Tetillidae (Porifera, Demospongiae, Spirophorida) based on three molecular markers.

Tetillidae are spherical to elliptical cosmopolitan demosponges. The family comprises eight genera: namely, Acanthotetilla Burton, 1959, Amphitethya Lendenfeld, 1907, CinachyraSollas, 1886, CinachyrellaWilson, 1925, Craniella Schmidt, 1870, Fangophilina Schmidt, 1880, Paratetilla Dendy, 1905, and Tetilla Schmidt, 1868. These genera are characterized by few conflicting morphological characters, resulting in an ambiguity of phylogenetic relationships. The phylogeny of tetillid genera was investigated using the cox1, 18S rRNA and 28S rRNA (C1-D2 domains) genes in 88 specimens (8 genera, 28 species). Five clades were identified: (i) Cinachyrella, Paratetilla and Amphitethya species, (ii) Cinachyrella levantinensis, (iii) Tetilla, (iv) Craniella, Cinachyra and Fangophilina and (v) Acanthotetilla. Consequently, the phylogenetic analysis supports the monophyly of Tetilla, a genus lacking any known morphological synapomorphy. Acanthotetilla is also recovered. In contrast, within the first clade, species of the genera Paratetilla and Amphitethya were nested within Cinachyrella. Similarly, within the fourth clade, species of the genera Cinachyra and Fangophilina were nested within Craniella. As previously postulated by taxonomists, the loss of ectodermal specialization (i.e., a cortex) has occurred several times independently. Nevertheless, the presence or absence of a cortex and its features carry a phylogenetic signal. Surprisingly, the common view that assumes close relationships among sponges with porocalices (i.e., surface depressions) is refuted.

Evaluation of anti-inflammatory and antinociceptive effects of D-002 (beeswax alcohols).

D-002, a mixture of six higher aliphatic alcohols purified from beeswax, displayed anti-inflammatory effects in carrageenan-induced pleurisy and cotton pellet granuloma in rats. The aim of the present study was to confirm the anti-inflammatory properties of D-002 and to explore its potential analgesic effects. Xylene-induced mouse ear oedema was used to assess the anti-inflammatory effect, acetic acid-induced writhing and hot plate responses for the analgesic activity, and the open field and horizontal rotarod tests for motor performance. For anti-inflammatory tests, mice were randomised into a negative vehicle control and five xylene-treated groups: the vehicle, D-002 (25, 50 and 200 mg/kg) and indomethacin 1 mg/kg (reference drug). Treatments were given for 15 days. Effects on oedema formation and myeloperoxidase (MPO) activity were tested. For analgesia and motor performance tests, mice were randomised into a vehicle control and D-002-treated groups (25, 50 and 200 mg/kg). Two sets of experiments were done, which included acute and repeat (15 days) dosing. D-002 (25, 50 and 200 mg/kg) significantly decreased xylene-induced ear oedema (44.7, 60.8 and 76.4%, respectively) and the increase of MPO activity induced by xylene (38.0, 47.0 and 57.0%, respectively), while indomethacin significantly inhibited xylene-induced oedema (59.9%) and MPO activity (57.5%). Single and repeat doses of D-002 (25, 50 and 200 mg/kg) decreased the acetic acid-induced writhing responses by 21.2, 28.2 and 40.1%, for the single doses; 25.2, 35.1 and 43.2%, respectively, for the repeat doses, but did not affect the hot plate, open field and rotarod behaviours. Aspirin 100 mg/kg significantly decreased acetic acid-induced abdominal constrictions and morphine (5 mg/kg) significantly increased the latency of the hot plate response. This study confirmed the anti-inflammatory effects of D-002 and demonstrated its analgesic effects on the acetic acid-induced writhing, but not on the hot plate response, which suggests that the antinociceptive effects of D-002 could be related to its anti-inflammatory activity.

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 percent), TOH (18.8 percent) and SH groups (31.6 percent), and the mean increase of TAS (35.3 percent) 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(AU)

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.

Assessment of the effects of D-003, a new antiplatelet and lipid-lowering compound, in healthy volunteers. A phase I clinical study.

OBJECTIVE: To investigate the effects of D-003 on the bleeding time (BT) and lipid profile of healthy human volunteers. METHODS: This single-blind, randomised, placebo-controlled, parallel-group study was conducted in healthy volunteers. Step 1 investigated the effects of single doses of D-003 5, 25 or 50 mg on BT in comparison with placebo. Step 2 investigated the effects of 30 days of D-003 5, 25 or 50 mg/day compared with placebo on lipid profile with an interim assessment at 14 days. BT, lipid profile, physical and haematological safety indicators were measured and adverse events (AEs) recorded. Both steps were followed by a 14- or 30-day washout period. RESULTS: Step 1: D-003 25 and 50 mg significantly increased mean BT 2 hours after administration compared with baseline, but a significant difference versus placebo occurred only with the 50 mg dose. Individual values from participants taking this dose, however, remained within normal limits. This effect was reversible. BT values obtained 2 hours after drug administration showed a moderate dose-dependent relationship. No drug-related changes in safety indicators were found with D-003. Step 2: After 7 days on D-003 50 mg/day, BT was significantly increased compared with baseline and placebo up to the end of the active treatment period. However, all individual values for participants taking this dosage remained within the normal range. This effect was reversible by the end of the washout period. After 30 days, D-003 (5, 25 and 50 mg/day) significantly reduced serum TC (by 13.3 to 17.4%) and LDL-C (by 11.6 to 22.6%) levels, and raised HDL-C levels (by 14.6 to 29.7%), but did not affect triglyceride levels. The significant increase in HDL-C was observed after 14 days on treatment. The effects on the lipid profile were reversible by the end of the 30-day washout period, although after 14 days of washout the effects on HDL-C and LDL-C still remained significant, revealing a certain persistence of effect. Eight participants (four receiving placebo and four receiving D-003 5, 25 or 50 mg/day) reported a total of nine AEs, none of which were drug-related. Of these patients, only two treated with D-003 25 and 50 mg/day discontinued treatment. CONCLUSIONS: D-003 in single or repeated doses (50 mg) induced significant and reversible increases in BT. In addition, repeated doses (5, 25 and 50 mg/day) significantly and reversibly lowered serum LDL-C and TC levels and significantly raised serum HDL-C levels. These effects were reversible by 30 days after the end of treatment.

Effects of policosanol on older patients with hypertension and type II hypercholesterolaemia.

OBJECTIVE: This study was conducted to investigate the effects of policosanol administered for 12 months on the lipid profile of older patients with hypertension and type II hypercholesterolaemia and no history of coronary heart disease (CHD) or cerebrovascular disease. PATIENTS AND PARTICIPANTS: 589 older male and female patients with hypertension and type II hypercholesterolaemia and no history of CHD or cerebrovascular disease were included. METHODS: This was a prospective, randomised, double-blind, placebo-controlled study in parallel groups treated with policosanol (5 to 10 mg/day) for 1 year. After 6 weeks on a standard step I cholesterol-lowering diet, 589 patients were randomised to policosanol (5 mg) or placebo tablets, to be taken once daily for 12 months. The dosage was doubled to 10 mg/day if total cholesterol values were > 6.1 mmol/L after 6 months of therapy. RESULTS: Policosanol significantly (p < 0.00001) lowered serum low-density lipoprotein-cholesterol (LDL-C) [20.5%], total cholesterol (TC) [15.4%], triglycerides (11.9%), LDL-C/high-density lipoprotein-cholesterol (HDL-C) ratio [22.2%] and TC/HDL-C ratio (20.1%), and increased (p < 0.0001) HDL-C (12.7%). The frequency of vascular and all-cause serious adverse events (SAEs) was lower (p < 0.05) in the policosanol recipients (two vascular SAEs, 0.7%; five all-cause SAEs, 1.7%) than in the placebo recipients (six vascular SAEs, 2.0%; 12 all-cause SAEs, 4.1%). Similarly, total adverse events (AEs) were less frequent in the policosanol-treated group (29; 9.8%) compared with the placebo group (52; 17.7%) [p < 0.01]. Three placebo recipients and no policosanol recipents died during the study as a result of myocardial infarction (two patients) and sudden cardiac arrest (one). Policosanol was well tolerated, and no drug-related disturbances in safety indicators were found. Policosanol significantly decreased systolic blood pressure (BP) compared with baseline and placebo, which could be an additional advantage in this population at high coronary risk. CONCLUSIONS: Policosanol administered long term is effective in lowering LDL-C and TC as well as increasing HDL-C levels in older patients with hypertension and type II hypercholesterolaemia without a history of CHD or cerebrovascular disease. In addition, policosanol treatment also shows benefits in the occurrence of SAEs of vascular aetiology, on the general AE profile and the reduction of BP in treated patients compared with baseline.