Effect of Terbinafine on the Pharmacokinetics of Cyclosporin in Humans

Cyclosporin is largely metabolized by hepatic cytochrome P450 enzymes, and azole drugs that inhibit cytochrome P450 may precipitate cyclosporin toxicity. The allylamine terbinafine binds to a small subfraction of hepatic cytochrome P450 in type I fashion, and has no effect upon hepatic metabolism of cyclosporin in vitro. The purpose of this study was to determine whether oral terbinafine alters the pharmacokinetics of oral cyclosporin in vivo.Twenty male volunteers (age 19–44 years), were randomly allocated to two groups. The first group received three single oral doses of cyclosporin 300mg at intervals of 21 d. The second and third doses of cyclosporin were preceded by a 6-d course of oral terbinafine 250mg each morning. A further 250mg of terbinafine was taken with the second and third doses of cyclosporin. Blood levels of cyclosporin and terbinafine were monitored for 36h after each dose. The second group received a 7-d course of terbinafine 250mg each morning. On the seventh day a single dose of cyclosporin 300mg was taken together with the terbinafine. Blood levels of both cyclosporin and terbinafine were monitored for 36kh. Two further single doses of cyclosporin 300mg were given at intervals of 2 weeks and the cyclosporin levels again monitored. In both groups each cyclosporin dose was preceded by an 8-h fast.The mean peak blood concentration of cyclosporin when taken alone was 958 μg/I, and 822 when taken with terbinafine. The mean area under the curve for cyclosporin was 4207 μg/l/h when taken alone and 3665 when taken with terbinafine. The mean absorption half-life for cyclosporin when taken alone was 0.29 h, and 0.33 when taken with terbinafine. The mean time of maximum concentration and elimination half-life of cyclosporin were unaltered by terbinafine. The results suggest that terbinafine is likely to prove a safe systemic anti-fungal treatment for patients who are taking cyclosporin

Post-dispersal probability of germination and establishment on the shorelines of slow-flowing or stagnant water bodies

Question: In Dutch fens, species that colonize open water and induce the formation of floating peat mats have become rare. Many such riparian pioneer species occur predominantly on shorelines sheltered from the wind, whereas the majority of seeds tend to be deposited on exposed shorelines, as seeds are dispersed via wind-driven waves and currents. Do differences in germination and seedling survival between sheltered and exposed shorelines explain this difference? Location: The fen reserve ‘De Westbroekse zodden’ (52 °10′ N; 5 °07′ E) Methods: With a sowing experiment, the germination, seedling survival and overall recruitment of Berula erecta, Calla palustris, Comarum palustre, Glyceria maxima and Mentha aquatica were studied on sheltered and wind-exposed banks in eight fen ponds. Temperature, light availability, water level, wave impact, litter and seed deposition and vegetation height were recorded over 16 wk. The probability of washing away was quantified with small seed mimics. With a greenhouse experiment, we separately examined the effects of environmental differences between sheltered and exposed banks. Results: In the field, compared to sheltered shorelines, exposed shorelines had a higherwave impact, higher light availability in spring andmore litter and seeds deposited on them. In the greenhouse experiment, only litter addition decreased germination. This effect was overridden in the field, where the higher light availability on exposed banks increased germination. In the field, the number of seedlings decreased strongly over time, and eventual recruitment was determined by the degree to which seeds and seedlings were washed away by wave action. The probability of being washed away was highest on exposed shorelines (where waves were larger), which resulted in higher recruitment on sheltered shorelines. Conclusions: The recruitment of colonizing species to fen pond shorelines is limited by the probability that seeds and seedlings may be washed into the open water. This process can eventually cause more successful recruitment on upwind or lee-side shorelines despite lower seed inputs there.

Multiple effects of land-use changes impede the colonization of open water in fen ponds

Question: Dutch fen areas have become embedded in intensively used landscapes, resulting in biodiversity loss. Hence, plant species that colonize open water inducing the formation of species-rich floating peat mats have disappeared. Despite many restoration efforts, they have not returned. Is natural succession towards floating mats impeded by site conditions, dispersal limitations or changed biotic interactions? Location: Six Dutch fen reserves: De Deelen, De Weerribben, De Wieden, Westbroek, Molenpolder and Terra Nova. Methods: In 62 fen ponds we determined plant species richness and expansion into open water. We related these to habitat quality (chemical composition of soil and surface water, pond morphology), dispersal potential (distance to remnant populations, likelihood of dispersal) and biotic interactions (presence of muskrats [Ondatra zibethicus L.] and the keystone species Stratiotes aloides). Results: Factor analysis showed that plants expanded further into open water and bank vegetation had higher species richness in areas with older ponds and lower muskrat densities. Locally, high turbidity hampered colonization. Whenever the water was clear, colonization was higher in shallow ponds, and in deep ponds only if Stratiotes was present. Species richness was negatively correlated to nutrient availability in soil and positively correlated to hydrological isolation (decreased sulphate concentrations). We also found that species richness was higher in sheltered banks. Conclusions: Multiple habitat characteristics (turbidity, water depth, nutrient and sulphate concentrations) and the influence of muskrats and Stratiotes all play a role in the lack of restoration success in Dutch fen ponds. Dispersal limitations seem to be overruled by habitat limitations, as colonization often fails even when sufficient propagule sources are present, or when connectivity is high

The role of wind in the dispersal of floating seeds in slow flowing or stagnant water bodies

Question What is the role of wind in the dispersal of waterborne seeds in slow-flowing and stagnant water bodies at different temporal and spatial scales? (i) Is there a direct effect of wind on seed dispersal speed and distance? (ii) Are prevailing wind conditions reflected in the seed deposition patterns during a year? (iii) What are the long-term (multiple year) effects of prevailing wind conditions on the pattern and composition of shoreline seed banks? Location The Westbroekse Zodden (52˚10N; 5˚07E) and De Weerribben (52°46N; 5°55E) fen reserves in The Netherlands. Methods Real-time seed movement tracking experiments were conducted at different wind speeds. Additionally, we performed a seed trap experiment using artificial grass mats and carried out seed bank analyses using a seedling emergence test. Results Wind speed and direction strongly determined the dispersal process and the resulting deposition patterns of floating seeds in shallow lakes or ponds. Wind speed directly influenced dispersal speed and distance. Increasing wind speed increased dispersal speed but decreased dispersal distance. Over multiple seasons, more seeds were deposited at downwind shorelines than at upwind shorelines, showing that wind-driven hydrochory resulted in directional transport according to the prevailing wind direction. The species composition of deposited seeds was also affected, with proportionally more water-dispersed seeds being deposited at down-wind shorelines. These effects of wind speed and directionality will have consequences for the colonization of riparian zones in lentic systems and, therefore, also influence management and restoration. In the long term, local seed banks in riparian zones reflected the prevailing wind conditions poorly, showing that additional processes, such as differential germination and predation, also play important roles at longer time scales. Conclusions Wind plays an important role in the dispersal of waterborne seeds in lentic systems and (prevailing) wind speed and direction are reflected in seed dispersal trajectories and deposition patterns.

Multiple effects of land-use changes impede the colonization of open water in fen ponds

Question: Dutch fen areas have become embedded in intensively used landscapes, resulting in biodiversity loss. Hence, plant species that colonize open water inducing the formation of species-rich floating peat mats have disappeared. Despite many restoration efforts, they have not returned. Is natural succession towards floating mats impeded by site conditions, dispersal limitations or changed biotic interactions? Location: Six Dutch fen reserves: De Deelen, De Weerribben, De Wieden, Westbroek, Molenpolder and Terra Nova. Methods: In 62 fen ponds we determined plant species richness and expansion into open water. We related these to habitat quality (chemical composition of soil and surface water, pond morphology), dispersal potential (distance to remnant populations, likelihood of dispersal) and biotic interactions (presence of muskrats [Ondatra zibethicus L.] and the keystone species Stratiotes aloides). Results: Factor analysis showed that plants expanded further into open water and bank vegetation had higher species richness in areas with older ponds and lower muskrat densities. Locally, high turbidity hampered colonization. Whenever the water was clear, colonization was higher in shallow ponds, and in deep ponds only if Stratiotes was present. Species richness was negatively correlated to nutrient availability in soil and positively correlated to hydrological isolation (decreased sulphate concentrations). We also found that species richness was higher in sheltered banks. Conclusions: Multiple habitat characteristics (turbidity, water depth, nutrient and sulphate concentrations) and the influence of muskrats and Stratiotes all play a role in the lack of restoration success in Dutch fen ponds. Dispersal limitations seem to be overruled by habitat limitations, as colonization often fails even when sufficient propagule sources are present, or when connectivity is high.

Day hospital versus intensive out-patient mentalisation-based treatment for borderline personality disorder:Multicentre randomised clinical trial

Background Two types of mentalisation-based treatment (MBT) have been developed and empirically evaluated for borderline personality disorder (BPD): day hospital MBT (MBT-DH) and intensive out-patient MBT (MBT-IOP). No trial has yet compared their efficacy.Aims To compare the efficacy of MBT-DH and MBT-IOP 18 months after start of treatment. MBT-DH was hypothesised to be superior to MBT-IOP because of its higher treatment intensity.Method In a multicentre randomised controlled trial (Nederlands Trial Register: NTR2292) conducted at three sites in the Netherlands, patients with BPD were randomly assigned to MBT-DH (n = 70) or MBT-IOP (n = 44). The primary outcome was symptom severity (Brief Symptom Inventory). Secondary outcome measures included borderline symptomatology, personality functioning, interpersonal functioning, quality of life and self-harm. Patients were assessed every 6 months from baseline to 18 months after start of treatment. Data were analysed using multilevel modelling based on intention-to-treat principles.Results Significant improvements were found on all outcome measures, with moderate to very large effect sizes for both groups. MBT-DH was not superior to MBT-IOP on the primary outcome measure, but MBT-DH showed a clear tendency towards superiority on secondary outcomes.Conclusions Although MBT-DH was not superior to MBT-IOP on the primary outcome measure despite its greater treatment intensity, MBT-DH showed a tendency to be more effective on secondary outcomes, particularly in terms of relational functioning. Patients receiving MBT-DH and MBT-IOP, thus, seem to follow different trajectories of change, which may have important implications for clinical decision-making. Longer-term follow-up and cost-effectiveness considerations may ultimately determine the optimal intensity of specialised treatments such as MBT for patients with BPD

A Holocene record of human induced and natural environmental change from Lake Forsyth (Te Wairewa), New Zealand

A 1.2 m sediment core from Lake Forsyth, Canterbury, New Zealand, records the development of the catchment/lake system over the last 7000 years, and its response to anthropogenic disturbance following European settlement c. 1840 AD. Pollen was used to reconstruct catchment vegetation history, while foraminifera, chironomids, Trichoptera, and the abundance of Pediastrum simplex colonies were used to infer past environmental conditions within the lake. The basal 30 cm of core records the transition of the Lake Forsyth Basin from a tidal embayment to a brackish coastal lake. Timing of closure of the lake mouth could not be accurately determined, but it appears that Lake Forsyth had stabilised as a slightly brackish, oligo-mesotrophic shallow lake by about 500 years BP. Major deforestation occurred on Banks Peninsula between 1860 AD and 1890 AD. This deforestation is marked by the rapid decline in the main canopy trees (Prumnopitys taxifolia (matai) and Podocarpus totara/hallii (totara/mountain totara), an increase in charcoal, and the appearance of grasses. At around 1895 AD, pine appears in the record while a willow (Salix spp.) appears somewhat later. Redundancy analysis (RDA) of the pollen and aquatic species data revealed a significant relationship between regional vegetation and the abundance of aquatic taxa, with the percentage if disturbance pollen explaining most (14.8%) of the constrained variation in the aquatic species data. Principle components analysis (PCA) of aquatic species data revealed that the most significant period of rapid biological change in the lakes history corresponded to the main period of human disturbance in the catchment. Deforestation led to increased sediment and nutrient input into the lake which was accompanied by a major reduction in salinity. These changes are inferred from the appearance and proliferation of freshwater algae (Pediastrum simplex), an increase in abundance and diversity of chironomids, and the abundance of cases and remains from the larvae of the caddisfly, Oecetis unicolor. Eutrophication accompanied by increasing salinity of the lake is inferred from a significant peak and then decline of P. simplex, and a reduction in the abundance and diversity of aquatic invertebrates. The artificial opening of the lake to the Pacific Ocean, which began in the late 1800s, is the likely cause of the recent increase in salinity. An increase in salinity may have also encouraged blooms of the halotolerant and hepatotoxic cyanobacteria Nodularia spumigena