Review: Marine natural products

This review covers the literature published in 2003 for marine natural products, with 619 citations (413 for the period January to December 2003) referring to compounds isolated from marine microorganisms and phytoplankton, green algae, brown algae, red algae, sponges, coelenterates, bryozoans, molluscs, tunicates and echinoderms. The emphasis is on new compounds (656 for 2003), together with their relevant biological activities, source organisms and country of origin. Biosynthetic studies or syntheses that lead to the revision of structures or stereochemistries have been included (78), including any first total syntheses of a marine natural product

Material Loss at the Head Taper Junction of the Metal-on-Metal Pinnacle Total Hip Replacement

Introduction The ASR XL (DePuy) total hip replacement (THR) is a notable example of a modern metal-on-metal (MOM) implant design that has demonstrated unacceptable survival rates, leading to its recall by the manufacturer; national joint registries have reported revision rates at 7 years of 40% when paired with the Corail stem [1]. The ASR XL THR has a considerably greater risk of revision than the ASR resurfacing hip, which used the same bearing design. This suggests that material loss at the head-stem junction may be responsible for the greater percentage of THR failures observed in this design. The Pinnacle MOM-THR (DePuy) however used the same Corail stem as the ASR XL THR but demonstrated better clinical results, with revision rates of less than 10% at 7 years [1]. The ASR XL and MOM Pinnacle are two designs that have been widely used in hip replacement surgery. The reasons for the differences in the failure rates of the two designs are not fully understood. Comparing the mechanisms of failure of both hips will help surgeons understand whether patients with MOM Pinnacle hips will experience the same types of problems as with those seen with the ASR XL. The aims of this retrieval study were to investigate the significance of differences between the ASR XL and MOM Pinnacle in relation to: (1) pre-revision whole blood Co/Cr ratios, (2) visual evidence of taper corrosion, (3) volumetric material loss at the bearing surfaces and (4) volumetric material loss at the taper surfaces. Methods This study involved a series of failed MOM hips consisting of the ASR XL (n=30) and Pinnacle (n=30), all that had been used with a Corail stem. The bearing material in each design was cobalt-chromium and the Corail stem is of a cementless titanium 12/14 design. The ASR XL and Pinnacle had a median head diameter of 47mm (39-55) and 36mm (36-40) respectively, and a median time to revision of 38.5 months (12-74) and 55 months (14-86) respectively. Pre-revision whole blood metal ion levels were collected for each Table 1 summarises patient and implant data for the hips in this study. The female taper surfaces of all 60 heads were examined macroscopically and microscopically to assess the severity of corrosion. Each surface was graded with a score of between 1 (no corrosion) and 4 (severe corrosion) using a well-published scoring system, which has been shown to be statistically reliable. A Zeiss Prismo (Carl Zeiss Ltd, Rugby, UK) coordinate measuring machine (CMM) was used to determine the volume of material loss at the cup and head bearing surfaces. Up to 300,000 data points were collected using a 2mm ruby stylus that was translated along 400 polar scan lines on the surface. The raw data was used to map regions of material loss by comparing with the unworn geometry of the bearing. A Talyrond 365 (Hobson, Leicester, UK) roundness measuring machine was used to measure the volumetric material loss at each of the head taper surfaces. Published protocols were used to take a series of 180 vertical traces along the taper surface using a 5μm diamond stylus; worn and unworn regions were mapped and used to calculate material loss. Neither the volumetric measurement data nor corrosion scores were normally distributed. Therefore non-parametric tests were performed to assess the statistical significance of differences between the two designs in relation to the parameters under investigation in this study. Results Both the whole blood Co ion levels and the Co/Cr ratios, Figure 1, of the ASR XL hips were significantly greater than the Pinnacles (p<0.05). There was no significant difference between the whole blood Cr ion levels between the two designs (p=0.0542). 18 of the ASR XL hips presented evidence of edge wearing of the cup, compared with 14 Pinnacle hips; this difference was not significant (p=0.438). The length of the stem trunnion contact engagement length with the taper was approximated as being 10.5mm for both designs. The median time to revision of the ASR XL hips was significantly less than the Pinnacle hips (p<0.01). There was visual evidence of corrosion in 93% (n=28) and 90% (n=27) of head tapers for the ASR XLs and Pinnacles respectively. Moderate to severe corrosion was observed in 67% (n=20) of ASR XLs compared to 60% (n=18) of Pinnacles. There was however no statistically significant difference between the scores of the two groups (p=0.927). Figure 2 presents the distribution of material loss rates for the bearing and taper surfaces of the two designs in this study. The median total bearing surface (combined cup and head) rate of material loss for the ASR XL and Pinnacle hips was 4.45mm3/year (0.32-22.85) and 4.03mm3/year (0.87-62.12) respectively. There was no significant difference between the two groups (p=0.928). The median material loss rate at the taper surfaces of the ASR XL and Pinnacle hips was 0.62mm3/year (0-4.20) and 0.30mm3/year (0-3.12); this difference was not significant (p=0.198). Discussion The work of this study presents comparisons of retrieval findings between the ASR XL and Pinnacle MOM-THRs; these hip designs were two of the most commonly implanted in patients worldwide. The significantly greater whole blood Co/Cr ratios found in the ASR XL group compared to the Pinnacle group are of interest. It is speculated that a Co/Cr ratio of greater than 1 may be an indicator of corrosion of an implant whereby more Cr ions are retained on the surface, whilst comparatively more Co ions are released into the blood. In the current study we found wear rates at the bearing surfaces of both designs to be comparable, suggesting that the significantly greater Co/Cr ratios in the ASR XL hips must be due to greater corrosion at the taper junction than the Pinnacles. Although the ASR XL hips had been implanted for a significantly shorter period of time, our visual assessment of the corrosion of the taper junctions found that corrosion scores were comparable between the two designs; indeed, a marginally greater number of ASR XL tapers had evidence of moderate to severe corrosion. This finding, coupled with the elevated Co/Cr ratios suggests that the ASR XL design is more susceptible to corrosion at the taper junction than the Pinnacle hip. We found that the median rate of material loss at the ASR XL taper was over twice that of the Pinnacle taper. Whilst not statistically significant, this difference may be due to a greater risk of corrosion at this interface in the ASR XL design. The differences in material loss and corrosion that were observed at the taper junctions may be explained by considering the larger head sizes of the ASR XL hips in comparison to the Pinnacles. It has previously been shown that increasing head size is correlated with greater visual evidence of corrosion and that increased frictional torque along the taper junction due a larger head diameter can increase the risk of fretting-corrosion. It is suggested therefore that the combination of the larger head sizes of the ASR XLs coupled with the comparatively short, rough surface of the Corail trunnion results in a cumulative effect leading to greater corrosion at the taper junction. Significance The results of the study suggest that the combination of (1) increased frictional torque in the larger ASR XLs and (2) the rough Corail trunnion surface, results in greater corrosion at the taper junction in comparison to the Pinnacle hips; this helps to explain the higher risk of revision in this hip design

The Isolation of a New S-Methyl Benzothioate Compound from a Marine-Derived Streptomyces sp.

The application of an HPLC bioactivity profiling/microtiter plate technique in conjunction with microprobe NMR instrumentation and access to the AntiMarin database has led to the isolation of a new 1. In this example, 1 was isolated from a cytotoxic fraction of an extract obtained from marine-derived Streptomyces sp. cultured on Starch Casein Agar (SCA) medium. The 1D and 2D 1H NMR and ESIMS data obtained from 20 μg of compound 1 fully defined the structure. The known 2 was also isolated and readily dereplicated using this approach

Trends in the Discovery of New Marine Natural Products from Invertebrates over the Last Two Decades – Where and What Are We Bioprospecting?

It is acknowledged that marine invertebrates produce bioactive natural products that may be useful for developing new drugs. By exploring untapped geographical sources and/or novel groups of organisms one can maximize the search for new marine drugs to treat human diseases. The goal of this paper is to analyse the trends associated with the discovery of new marine natural products from invertebrates (NMNPI) over the last two decades. The analysis considers different taxonomical levels and geographical approaches of bioprospected species. Additionally, this research is also directed to provide new insights into less bioprospected taxa and world regions. In order to gather the information available on NMNPI, the yearly-published reviews of Marine Natural Products covering 1990–2009 were surveyed. Information on source organisms, specifically taxonomical information and collection sites, was assembled together with additional geographical information collected from the articles originally describing the new natural product. Almost 10000 NMNPI were discovered since 1990, with a pronounced increase between decades. Porifera and Cnidaria were the two dominant sources of NMNPI worldwide. The exception was polar regions where Echinodermata dominated. The majority of species that yielded the new natural products belong to only one class of each Porifera and Cnidaria phyla (Demospongiae and Anthozoa, respectively). Increased bioprospecting efforts were observed in the Pacific Ocean, particularly in Asian countries that are associated with the Japan Biodiversity Hotspot and the Kuroshio Current. Although results show comparably less NMNPI from polar regions, the number of new natural products per species is similar to that recorded for other regions. The present study provides information to future bioprospecting efforts addressing previously unexplored taxonomic groups and/or regions. We also highlight how marine invertebrates, which in some cases have no commercial value, may become highly valuable in the ongoing search for new drugs from the sea

Charactering taper junction wear helps understand the mechanism of failure of metal on metal hip replacements.

Introduction: Taper junction material loss is the result of corrosion and mechanical wear. The significance of the taper junction material loss is highlighted by studies that compared resurfacing and total hip replacements of the same type and size. High volumes of material loss are reported, especially from the head taper, but the pattern of wear is unknown. One report characterized the material loss pattern of five tapers (n=5) into axisymmetrical and asymmetrical, along the long axis of the taper. We noticed more than two patterns on our retrievals and we set out to characterize these types and relate them to clinical variables. Methods: We retrospectively analysed retrieved cobalt-chromium tapers (n=146) using a roundness measurement machine. We also performed a corrosion classification and collected clinical data (metal ion levels, time to revision, component sizes). A non-blinded author devised a four-group classification (table). Two blinded authors classified the material loss patterns derived from the roundness measurement machine. Results: The four groups of material loss patterns Low wear (n= 62), Open-end band (n=29), Stripped material loss (n=51) and Coup-Countercoup (n=4). Kappa was 0.78 (p<0.001) in the assessment of interobserver reliability. Kruskal-Wallis test revealed: - Significantly higher volumes of wear on the taper of Stripped material loss compared to Low wear (p<0.001) and Open-end band compared to Low wear (p<0.001) groups. - Significantly higher chromium ion blood levels in the open-end band compared to the Stripped material loss group. - Significantly higher Cobalt ion blood levels in the Stripped material loss compared to the Low wear group - Significantly higher Cobalt/Chromium ration in the Open-end band compared to the Low wear group One-way ANOVA analysis revealed: - Significant difference between in the head sizes between the groups (p=0.01). Post-hoc analysis located the difference between the Low wear (median=40, range=20) and Open-end band (median=49, range=20) groups (p<0.001). - Significantly higher time to revision in the Stripped material loss compared to the Low wear group (p=0.05), in the post-hoc analysis. - Significantly higher corrosion scores in the Stripped material loss compared to the Low wear group (p<0.001) and the Open-end band compared to the Low wear group (p<0.001). Discussion: The results suggests that corrosion becomes worse over time and that the material loss pattern evolves gradually from the Low wear to Open-end band and finally to Stripped. Further analysis is required to assess the factors that affect the Coup-countercoup group

Characterisation of Wear Morphology at the Head Cup Bearing Interface in Retrieved Metal-on-Metal Hip Replacements

Abstract Background The changes in surface roughness occurring during the wear process at the bearing surface are of great importance in trying to understand the failure mechanism of large head metal-on-metal hip replacements. The aim of the study is to identify and characterise the areal surface parameter variation between the worn and unworn areas. Surface topography variations at the bearing surface have an effect on the lubrication regime [1]. In vitro tests of these components have suggested a “self-polishing” of the surface [2]. Traditionally Ra has been used as a descriptor of surface texture. Considering the high standard of manufacturing to which these components are produced, Ra is not sufficient to describe surface morphology which requires spatial information which can only be achieved through the use of areal parameters. Methods A total of 50 retrieved metal-on-metal hip replacements were assessed using white light scanning interferometry (Talysurf CCI, Ametek, UK) to determine the difference in the areal surface topography parameters between the worn and unworn regions of the bearing surface. The worn area was identified by use of a previously described method [3] to produce a wear map of the bearing surface, this allows the identification of the regions of interest. A series of six measurements were taken on each component (figure 1) comprising of: 2 measurements at the equator of the head representing the unworn region, one measurement at the pole and just off centre from the pole and the rest of the measurements were taken inside and at the boundary of the wear area. Each measurement covered an area of 1 mm2 therefore it is crucial that the location of the measurement be established as accurately as possible. Data was analysed to determine the most relevant parameters that could be used to describe and highlight the changes in surface roughness that occur during the wear process. Discussion The measurement methodology developed shows a clear correlation between the areal surface parameters and the wear regions. The parameters show that areas of wear can be identified when the correct suite of parameters are utilised. This information is invaluable in developing a more advanced model of change in the lubrication regimes due to morphological changes during wear

Marine natural products

This review covers the literature published in 2014 for marine natural products (MNPs), with 1116 citations (753 for the period January to December 2014) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1378 in 456 papers for 2014), together with the relevant biological activities, source organisms and country of origin. Reviews, biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included

Advancement into the Arctic Region for Bioactive Sponge Secondary Metabolites

Porifera have long been a reservoir for the discovery of bioactive compounds and drug discovery. Most research in the area has focused on sponges from tropical and temperate waters, but more recently the focus has shifted to the less accessible colder waters of the Antarctic and, to a lesser extent, the Arctic. The Antarctic region in particular has been a more popular location for natural products discovery and has provided promising candidates for drug development. This article reviews groups of bioactive compounds that have been isolated and reported from the southern reaches of the Arctic Circle, surveys the known sponge diversity present in the Arctic waters, and details a recent sponge collection by our group in the Aleutian Islands, Alaska. The collection has yielded previously undescribed sponge species along with primary activity against opportunistic infectious diseases, malaria, and HCV. The discovery of new sponge species and bioactive crude extracts gives optimism for the isolation of new bioactive compounds from a relatively unexplored source