Pharmaceutical and nutraceutical management of canine osteoarthritis: present and future perspectives

Osteoarthritis (OA) is one of the most common chronic musculoskeletal diseases and causes of lameness in the dogs. The osteoarthritic disease process involves the entire synovial joint, encompassing the synovium, cartilage and underlying bone. Joint failure results from an abnormal mechanical strain causing damage to normal tissue or failure of pathologically impaired articular cartilage and bone under the influence of normal physiological strain or a combination of both. In both cases, the end point is cartilage loss and joint impairment. Osteoarthritic chondrocytes show an altered phenotype characterised by an excess production of catabolic factors, including metalloproteinases and reactive oxygen species. These factors constitute potential therapeutic targets and some new drugs and nutraceuticals have been proposed to promote the return to homeostasis. Until now, the therapeutic management of OA in dogs has been dominated by nonsteroidal anti-inflammatory drugs, but some new compounds, including diacerhein, with potential structure-modifying effects, are already used to treat OA in humans and could be helpful to manage OA in the dog. In addition, novel nutraceuticals, such as avocado/soybean unsaponifiable substances, have shown symptomatic effects in knee OA in humans, and could offer an alternative to prevent OA progression. This paper provides an overview of recent discoveries in the pathophysiology and in the therapeutic management of osteoarthritis in dogs.     

Molecular characterization of <Emphasis Type="Italic">Pythium</Emphasis> group F isolates by ribosomal-and intermicrosatellite-DNA regions analysis

Pythium group F is a ubiquitous, though minor, pathogen in several soilless and soil cultures; investigations were carried out to analyze different regions of the DNA and better understand the nature of this group. Fourty-two isolates were obtained from a variety of plants (cucumber, lettuce, tomato) grown in soil or soilless cultures collected in various countries (Canada, Denmark, France, Norway, Sweden and United Kingdom). All Pythium group F isolates displayed amplified ITS1-5,8S-ITS2 ribosomal DNA region (rDNA) of similar length, whereas polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) revealed that, among the seven enzymes used, polymorphism was only identified with Hin6I. After cloning of ITS1-5,8S-ITS2 rDNA region from Pythium group F isolates that displayed restriction polymorphism patterns with Hin6I, comparisons of sequence and restriction mapping data showed a slight variation consisting in a single base change. Inter Simple Sequence Repeat (ISSR)-PCR method was also used to obtain data related to the entire genome and not only to a single DNA region. It identified repeated motifs in the genome of Pythium group F isolates. Two primers (CAC)₅ and (CCA)₅ detected polymorphism, and isolates were classified among 11 molecular clusters. The genetic diversity of this group was not correlated with the geographical locations or the host plants from which the isolates originated. Polymorphism of Pythium group F isolates pointed out by ISSR is discussed     

Pharmacokinetics of meloxicam in plasma and urine of horses

OBJECTIVE: To determine pharmacokinetic parameters for meloxicam, a nonsteroidal anti-inflammatory drug, in horses. ANIMALS: 8 healthy horses. PROCEDURE: In the first phase of the study, horses were administered meloxicam once in accordance with a 2 x 2 crossover design (IV or PO drug administration; horses fed or not fed). The second phase used a multiple-dose regimen (daily oral administration of meloxicam for 14 days), with meloxicam administered at the recommended dosage (0.6 mg/kg). Plasma and urine concentrations of meloxicam were measured by use of validated methods with a limit of quantification of 10 ng/mL for plasma and 20 ng/mL for urine. RESULTS: Plasma clearance was low (mean +/- SD; 34 +/- 0.5 mL/kg/h), steady-state volume of distribution was limited (0.12 +/- 0.018 L/kg), and terminal half-life was 8.54 +/- 3.02 hours. After oral administration, bioavailability was nearly total regardless of feeding status (98 +/- 12% in fed horses and 85 +/- 19% in nonfed horses). During once-daily administration for 14 days, we did not detect drug accumulation in the plasma. Meloxicam was eliminated via the urine with a urine-to-plasma concentration that ranged from 13 to 18. Concentrations were detected for a relatively short period (3 days) after administration of the final daily dose. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study support once-daily administration of meloxicam regardless of the feeding status of a horse and suggest a period of at least 3 days before urine concentrations of meloxicam reach concentrations that could be used in drug control programs.     

Global mineralogical and aqueous mars history derived from OMEGA/Mars Express data

Global mineralogical mapping of Mars by the Observatoire pour la Mineralogie, l'Eau, les Glaces et l'Activité (OMEGA) instrument on the European Space Agency's Mars Express spacecraft provides new information on Mars' geological and climatic history. Phyllosilicates formed by aqueous alteration very early in the planet's history (the "phyllocian" era) are found in the oldest terrains; sulfates were formed in a second era (the "theiikian" era) in an acidic environment. Beginning about 3.5 billion years ago, the last era (the "siderikian") is dominated by the formation of anhydrous ferric oxides in a slow superficial weathering, without liquid water playing a major role across the planet.     

Impaired control of IRES-mediated translation in X-linked dyskeratosis congenita

The DKC1 gene encodes a pseudouridine synthase that modifies ribosomal RNA (rRNA). DKC1 is mutated in people with X-linked dyskeratosis congenita (X-DC), a disease characterized by bone marrow failure, skin abnormalities, and increased susceptibility to cancer. How alterations in ribosome modification might lead to cancer and other features of the disease remains unknown. Using an unbiased proteomics strategy, we discovered a specific defect in IRES (internal ribosome entry site)-dependent translation in Dkc1(m) mice and in cells from X-DC patients. This defect results in impaired translation of messenger RNAs containing IRES elements, including those encoding the tumor suppressor p27(Kip1) and the antiapoptotic factors Bcl-xL and XIAP (X-linked Inhibitor of Apoptosis Protein). Moreover, Dkc1(m) ribosomes were unable to direct translation from IRES elements present in viral messenger RNAs. These findings reveal a potential mechanism by which defective ribosome activity leads to disease and cancer.     

Anthocyanin and flavonoid production from Perilla frutescens: pilot plant scale processing including cross-flow microfiltration and reverse osmosis

Extraction and concentration at a pilot plant scale of anthocyanins and flavonoids from Perilla frutescens var. frutescens harvested in the Guangzhou area of China were investigated. The study of extraction efficiency using mineral acids and organic acids showed that 0.01 mol/L nitric acid was the most suitable to extract flavonoids from this slightly red leaf cultivar. The red extract contained 12 mg/L (as cyanidin equivalent) anthocyanins and other flavones. The multistep process included cross-flow microfiltration (CFM) with a ceramic type membrane, reverse osmosis (RO), and rotating evaporation (RE). The filtration fluxes were high and constant for CFM (150 L/h/m2 at 0.6 b) and for RO (22 L/h/m2 at 40 b). The red extract was concentrated 9.4 times by RO and then 5.4 times by RE. It contained 422 mg/L anthocyanins, representing 77% of the total extracted anthocyanin. The proportion of flavonoids was found unchanged during processing. The concentrated extract showed a pH of 2.7, and its free acidity was found to be 46% of the acidity added for extraction, because of the buffering capacity of the extract. At the concentration level reached, a crystallized deposit occurred and was identified as tartrate.     

Extraction, detection, and quantification of flavano-ellagitannins and ethylvescalagin in a Bordeaux red wine aged in oak barrels

An extraction procedure and an analytical method have been developed to detect and quantify for the first time a series of ellagitannin derivatives formed in wine during aging in oak barrels. The method involves a preliminary purification step on XAD7 HP resin followed by a second purification step on TSK 40 HW gel. The resulting extract is analyzed for compound identification and quantitative determination by high-performance liquid chromatography-electrospray ionization-mass spectrometry in single ion recording mode. Reference compounds, which are accessible through hemisynthesis from the oak C-glycosidic ellagitannin vescalagin, were used to build calibration curves, and chlorogenic acid was selected as an internal standard. This method enabled us to estimate the content of four flavano-ellagitannins and that of another newly identified wine polyphenol, beta-1-O-ethylvescalagin, in a Bordeaux red wine aged for 18 months in oak barrels. All five ellagitannin derivatives are derived from the nucleophilic substitution reaction of vescalagin with the grape flavan-3-ols catechin and epicatechin or ethanol.     

Laryngeal mask airway insertion requires less propofol than endotracheal intubation in dogs

OBJECTIVE: To compare the doses of propofol required for insertion of the laryngeal mask airway (LMA) with those for endotracheal intubation in sedated dogs. STUDY DESIGN: Randomized prospective clinical study. Animals Sixty healthy dogs aged 0.33-8.5 (3.0 +/- 2.3, mean +/- SD) years, weighing 2.2-59.0 (23.4 +/- 13.6, mean +/- SD) kg, presented for elective surgery requiring inhalation anaesthesia. METHODS: Animals were randomly assigned to receive either a LMA or an endotracheal tube. Pre-anaesthetic medication was intravenous (IV) glycopyrrolate (0.01 mg kg(-1)) medetomidine (10 microg kg(-1)) and butorphanol (0.2 mg kg(-1)). Repeated IV propofol injections (1 mg kg(-1) in 30 seconds) were given until LMA insertion or endotracheal intubation was achieved, when the presence or absence of laryngospasm, the respiratory rate (fr) and the total dose of propofol used were recorded. RESULTS: The total propofol dose (mean +/- SD) required for LMA insertion (0.53 +/- 0.51 mg kg(-1)) was significantly lower than for endotracheal intubation (1.43 +/- 0.57 mg kg(-1)). The LMA could be inserted without propofol in 47% of dogs; the remainder needed a single 1 mg kg(-1) bolus (n = 30). Endotracheal intubation was possible without propofol in 3.3% of the dogs, 47% needed one bolus and 50% required two injections (n = 30). The f(r) (mean +/- SD) was 18 +/- 6 and 15 +/- 7 minute(-1) after LMA insertion and intubation, respectively. CONCLUSION AND CLINICAL RELEVANCE: Laryngeal mask airway insertion requires less propofol than endotracheal intubation in sedated dogs therefore propofol-induced cardiorespiratory depression is likely to be less severe. The LMA is well tolerated and offers a less invasive means of securing the upper airway.     

Factors Responsible for the Co-occurrence of Forested and Unforested Rock Outcrops in the Boreal Forest

Rock outcrops in the boreal forest of Québec can show either of two different states: a forested state with >25% tree cover, and an unforested state (<25% tree cover). We tested three different hypotheses that might explain the co-occurrence of forested and unforested rock outcrops: (1) differences in bedrock geology, with unforested outcrops associated to bedrock types inimical to tree growth; (2) unforested outcrops as recently disturbed sites undergoing secondary succession towards a forested state; (3) unforested outcrops as an alternative stable state to forested outcrops, induced by post-fire regeneration failure. Digitized forest inventory maps were used along with bedrock geology maps and time-since-fire maps to compare forested and unforested outcrops for bedrock geology type and date of the last fire. Field surveys were conducted on 28 outcrops (14 forested, 14 unforested) to gather information regarding tree species composition and site characteristics (thickness of the organic matter layer, percent cover of lichens, mosses and ericaceous shrubs). None of the three hypotheses explain the co-occurrence of forested and unforested rock outcrops in the boreal forest of Québec. Both outcrop types occur on the same bedrock geology types. Unforested outcrops are not recently disturbed sites in early-successional states, as no clear distinction could be made in tree species composition and date of the last fire between the two outcrop types. Forested and unforested outcrops are not alternative stable states, as unforested outcrops are unstable and cannot maintain themselves through time in the prolonged absence of fire. Hence, unforested rock outcrops could be viewed as degraded, diverging post-fire types maintained by the late Holocene disturbance regime, characterized by high fire frequencies.     

Why are there so many species of herbivorous insects in tropical rainforests?

Despite recent progress in understanding mechanisms of tree species coexistence in tropical forests, a simple explanation for the even more extensive diversity of insects feeding on these plants has been missing. We compared folivorous insects from temperate and tropical trees to test the hypothesis that herbivore species coexistence in more diverse communities could reflect narrow host specificity relative to less diverse communities. Temperate and tropical tree species of comparable phylogenetic distribution supported similar numbers of folivorous insect species, 29.0 +/- 2.2 and 23.5 +/- 1.8 per 100 square meters of foliage, respectively. Host specificity did not differ significantly between community samples, indicating that food resources are not more finely partitioned among folivorous insects in tropical than in temperate forests. These findings suggest that the latitudinal gradient in insect species richness could be a direct function of plant diversity, which increased sevenfold from our temperate to tropical study sites.