Tiludronate treatment improves structural changes and symptoms of osteoarthritis in the canine anterior cruciate ligament model

Introduction

The aim of this prospective, randomized, controlled, double-blind study was to evaluate the effects of tiludronate (TLN), a bisphosphonate, on structural, biochemical and molecular changes and function in an experimental dog model of osteoarthritis (OA).

Methods

Baseline values were established the week preceding surgical transection of the right cranial/anterior cruciate ligament, with eight dogs serving as OA placebo controls and eight others receiving four TLN injections (2 mg/kg subcutaneously) at two-week intervals starting the day of surgery for eight weeks. At baseline, Week 4 and Week 8, the functional outcome was evaluated using kinetic gait analysis, telemetered locomotor actimetry and video-automated behaviour capture. Pain impairment was assessed using a composite numerical rating scale (NRS), a visual analog scale, and electrodermal activity (EDA). At necropsy (Week 8), macroscopic and histomorphological analyses of synovium, cartilage and subchondral bone of the femoral condyles and tibial plateaus were assessed. Immunohistochemistry of cartilage (matrix metalloproteinase (MMP)-1, MMP-13, and a disintegrin and metalloproteinase domain with thrombospondin motifs (ADAMTS5)) and subchondral bone (cathepsin K) was performed. Synovial fluid was analyzed for inflammatory (PGE₂ and nitrite/nitrate levels) biomarkers. Statistical analyses (mixed and generalized linear models) were performed with an α-threshold of 0.05.

Results

A better functional outcome was observed in TLN dogs than OA placebo controls. Hence, TLN dogs had lower gait disability (P = 0.04 at Week 8) and NRS score (P = 0.03, group effect), and demonstrated behaviours of painless condition with the video-capture (P < 0.04). Dogs treated with TLN demonstrated a trend toward improved actimetry and less pain according to EDA. Macroscopically, both groups had similar level of morphometric lesions, TLN-treated dogs having less joint effusion (P = 0.01), reduced synovial fluid levels of PGE₂ (P = 0.02), nitrites/nitrates (P = 0.01), lower synovitis score (P < 0.01) and a greater subchondral bone surface (P < 0.01). Immunohistochemical staining revealed lower levels in TLN-treated dogs of MMP-13 (P = 0.02), ADAMTS5 (P = 0.02) in cartilage and cathepsin K (P = 0.02) in subchondral bone.

Conclusion

Tiludronate treatment demonstrated a positive effect on gait disability and joint symptoms. This is likely related to the positive influence of the treatment at improving some OA structural changes and reducing the synthesis of catabolic and inflammatory mediators.     

The fine-scale population dynamics of spruce budworm: survival of early instars related to forest condition

Abstract.  1. A lagged, density-dependent relationship between survival of early instars and host-tree condition is revealed during outbreaks of spruce budworm, Choristoneura fumiferana Clem. Persistent damage to hosts leads to deterioration of the stand.
2. Resource limitation affects survival during early-instar dispersal of spruce budworm. Impediments to distinguishing these events with estimates of survival were overcome with a simple model that describes the dispersal and survival processes. The model was used to analyse a recent 15-year population series from Black Sturgeon Lake and two historical datasets from Green River, in Canada.
3. Defoliation-induced damage to the trees resulted in increased losses of spring-emerging larvae that are dispersing in search of feeding sites. Losses were further exacerbated by biotic factors such as maternal fecundity, rates of infection by the pathogen, Nosema fumiferanae , and by weather-related effects on the foraging period.
4. Survival of early-stage budworm larvae in persistent outbreaks declined and the likelihood of other density-related factors such as rate of mortality from natural enemies increased. These results may reconcile outstanding differences in interpretation of the role of the forest resource in spruce budworm population dynamics and point to a common process linking the dynamics of other well-known budworm species.     

悬钩子属植物化学成分及药理活性研究进展

本文对近10年来悬钩子属植物的化学成分和药理活性研究进行了综述,为该属植物的进一步开发利用提供参考。悬钩子属植物的化学成分主要包括黄酮、萜、鞣质、甾等。药理活性主要包括抗菌、抗炎、抗肿瘤、抗氧化、抗过敏、保肝、镇痛等。     

An NMR spectroscopy study of bendaline-albumin interactions

The complete assignment of the 1H and 13C NMR spectra of bendaline (BNDL) was performed by mono-dimensional and homo- and hetero-correlated two-dimensional NMR experiments. The interaction between bendaline and albumin was also studied by the analysis of the motional parameters spin-lattice relaxation times, allowing the motional state of the BNDL free and bound with albumin to be defined. In absence of albumin the indazolacetic and benzylic moieties are characterized by roughly the same mobility and by positive sigma (cross-relaxation rates) values. In the presence of the macromolecule, the indazolacetic and benzylic moieties and the lysine change their motional behaviour to different extents, as indicated by correlation times. Data obtained in absence and in presence of the protein show that the molecular moiety of the bendaline most involved in the binding with albumin is the fragment H-4 H-5. The binding constant was evaluated at 2.4x10(3)M(-1).     

Form and environment of Gryphaea arcuata

Gryphaea arcuata is one of the most studied fossils, but its detailed palaeoecology has been largely neglected. Specimens were collected within a short stratigraphic range (three ammonite zones) in the 'Calcaire à gryphées' of Xeuilley (Lorraine, France) dated Hettangian to Lower Sinemurian. As far as possible, they were sampled from each marly bed of the section. A biometric study and an isotopic analysis are compared in regard to organic matter measurements and palynological data, the results demonstrating a clear relationship between the shape of G. arcuata and environmental parameters. Factors responsible for the various shapes are temperature, oxygen levels on the sea floor and nutrient levels. Two main morphotypes can be related to two kinds of environment. In the first, controlled by a relatively hot and humid climate and tending towards eutrophication, the growth rate of Gryphaea was low, and the shells small, wide and thin. In the second environment, cooler than the first one and closer to the optimal living conditions of G. arcuata, the shell was large, thick and narrow, and exhibited a high growth rate.     

Oxygen metabolism,oxidative stress and acid-base physiology of dental plaque biofilms

Dental plaque is a natural biofilm which has been a focus of attention for many years because of its known roles in caries and periodontal diseases. Acid production by plaque bacteria leads to the erosion of tooth mineral in caries, and the cariogenicity of plaque is related to population levels of acid-tolerant organisms such as mutants streptococci. However, the biofilm character of plaque allows for survival of a diverse flora, including less acid-tolerant organisms, some of which can produce ammonia from arginine or urea to counter acidification. Plaque is often considered to be relatively anaerobic. However, evidence is presented here that both supragingival and subgingival plaque have active oxygen metabolism and that plaque bacteria, including anaerobes, have developed defenses against oxidative stress. Even in subgingival plaque associated with periodontitis, measured residual oxygen levels are sufficient to allow for oxygen metabolism by organisms considered to be extremely anaerobic such asTreponema denticola, which metabolizes oxygen by means of NADH oxidases and produces the protective enzymes superoxide dismutase and NADH peroxidase. The finding that plaque bacteria produce a variety of protective enzymes is a good indicator that oxidative stress is a part of their everyday life. The biofilm character of plaque allows for population diversity and coexistence of aerobes, anaerobes and microaerophiles. Overall, agents that affect oxidative metabolism offer possibilities for reducing the pathogenic activities of plaque.     

Chromosomal localization of a tandemly repeated DNA sequence in Trifolium repens L

INTRoDUCTIoNlYho1iumrePensL,whiteclover,isaneconomicallyimportantplantspeciesintemperatepastures.Asbrieflyreportedby[1],ithas16pairsofchromosomes(2n=32).Asyet,nodetailedcytologicalexaminationofthisspecies,suchasC-banding,hasbeenrep0rted.Inthelastdecade,thetechnique0fC-bandinghasbeenusedt0examinehighlyrepeatedsequencesinplantchrom0s0mesandhasprovidedausefultoolf0rtheanalysis0fcyt0geneticstructureincr0pplants[2-71.Inplants,thechr0m0s0mall0calizationofhighlyrepeatedDNAsequencesbyinsituhybr…     

Site selection by swans wintering in Britain and Ireland; the importance of habitat and geographic location

Monthly surveys of Bewick's Swans Cygnus columbianus bewickii , Whooper Swans Cygnus cygnus and Mute Swans Cygnus olor in Britain and Ireland were made during the 1990–1991 winter to determine factors affecting the swans' selection of feeding sites. Geographic location and habitat both influenced site selection. Whooper Swans occurred in greatest numbers at sites in Scotland, northeastern England and Northern Ireland, whereas Bewick's Swans had a more southerly distribution, reflecting differences in the migratory routes used by these two species. The resident Mute Swans were more widespread, with large flocks occurring in southeastern England and in parts of Scotland. Whooper and Mute Swans were found mainly on permanent inland waters (68% and 61%, respectively), but the majority of Bewick's Swans (60%) were on arable land. The percentage of Bewick's Swan flocks found on permanent inland waters (42%) was higher than that found on arable fields (23%), indicating that the large number recorded on arable land was a result of the birds congregating at a comparatively small number of sites. Overall, less than 15% of Whooper Swans and 3% of Mute Swans were on arable crops during the winter, but the largest flocks were associated with arable land for all three species. Thus, although the occurrence of large flocks at particular arable sites may give an impression that swans feed mainly on farmland, the swans are in fact more widely dispersed. Regional variation in the percentage of juveniles present was recorded for all three species. Changes during the winter in the distribution of juveniles, and of the swans as a whole, are considered in relation to food supply and to migratory routes for the Bewick's and Whooper Swans.