Continuous low-dose oral chemotherapy for adjuvant therapy of splenic hemangiosarcoma in dogs

BACKGROUND: Hemangiosarcoma (HSA) is a highly metastatic and often rapidly fatal tumor in dogs. At present, conventional adjuvant chemotherapy provides only a modest survival benefit for treated dogs. Continuous oral administration of low-dose chemotherapy (LDC) has been suggested as an alternative to conventional chemotherapy protocols. Therefore, we evaluated the safety and effectiveness of LDC using a combination of cyclophosphamide, etoposide, and piroxicam as adjuvant therapy for dogs with stage II HSA. HYPOTHESIS: We hypothesized that oral adjuvant therapy with LDC could be safely administered to dogs with HSA and that survival times would be comparable to those attained with conventional doxorubicin (DOX) chemotherapy. ANIMALS: Nine dogs with stage II splenic HSA were enrolled in the LDC study. Treatment outcomes were also evaluated retrospectively for 24 dogs with stage II splenic HSA treated with DOX chemotherapy. METHODS: Nine dogs with stage II splenic HSA were treated with LDC over a 6-month period. Adverse effects and treatment outcomes were determined. The pharmacokinetics of orally administered etoposide were determined in 3 dogs. Overall survival times and disease-free intervals were compared between the 9 LDC-treated dogs and 24 DOX-treated dogs. RESULTS: Dogs treated with LDC did not develop severe adverse effects, and long-term treatment over 6 months was well-tolerated. Oral administration of etoposide resulted in detectable plasma concentrations that peaked between 30 and 60 minutes after dosing. Both the median overall survival time and the median disease-free interval in dogs treated with LDC were 178 days. By comparison, the overall survival time and disease-free interval in dogs treated with DOX were 133 and 126 days, respectively. CONCLUSIONS: Continuous orally administered LDC may be an effective alternative to conventional high-dose chemotherapy for adjuvant therapy of dogs with HSA.     

Preliminary studies on the effectiveness of the novel pulicide, spinosad, for the treatment and control of fleas on dogs

Spinosad is a novel mode-of-action insecticide produced from a family of natural products derived from fermentation of the actinomycete, Saccharopolyspora spinosa. Separate studies were undertaken to determine the minimum effective dose of spinosad given orally for the treatment of experimentally induced flea infestations (Ctenocephalides felis) on dogs, and to assess any potential impacts of feeding canned or dry food at the time of dosing. Both were randomized block (blocked by gender and pre-treatment flea counts), blinded parallel-arm studies, with dogs selected on health and ability to maintain pre-treatment flea populations. For dose selection, 48 dogs were allocated among six groups (8 dogs/group; 4 males, 4 females): placebo-treated negative control, spinosad in gelatin capsules at 15, 20, 30 and 40 mg/kg administered per os; and topical imidacloprid (10 mg/kg) as a positive control. Placebo and spinosad treatments were administered on Days 0, 30 and 60, imidacloprid only on Day 0. In a second study to assess the impact of food type at the time of dosing, three groups were formed: placebo-treated control (8 dogs; 4 males, 4 females), spinosad (30 mg/kg) administered with canned food (8 male dogs, 8 females); and spinosad (30 mg/kg) with dry food (8 males, 8 females). Treatments were administered on Days 0 and 30. To assess post-treatment persistent efficacy, flea infestations were repeated at regular post-treatment intervals, beginning on Day 5 through Day 89 in the dose selection study and Day 58 in the impact of food type and dosing study. Flea counts were performed 48 h post-infestation by study personnel who were blinded to treatments. In the dose selection study, compared to geometric mean live flea counts in the control group, each spinosad dose was highly effective (99.8–100%) at 7, 14 and 21 days after treatment. Only the 30 and 40 mg/kg doses maintained high efficacy (97.2–100%) until 30 days after treatment, with no difference between the two. Imidacloprid was highly effective at Day 30, with significant difference only from the 15 mg/kg spinosad group. Because there was no significant difference between the higher spinosad rates, 30 mg/kg was selected as the optimal minimum effective dose. In the second study, spinosad was highly effective at all post-treatment flea counts (98–100%). Taken together, these studies demonstrate that repeated monthly oral treatments with spinosad at 30 mg/kg provide sustained control of C. felis on dogs. There were no treatment-related adverse events in either study, indicating that spinosad has potential to be used monthly as a safe and effective flea adulticide, providing sustained activity that matches that of currently used topical products.     

Crystal structure of a shark single-domain antibody V region in complex with lysozyme

Cartilaginous fish are the phylogenetically oldest living organisms known to possess components of the vertebrate adaptive immune system. Key to their immune response are heavy-chain, homodimeric immunoglobulins called new antigen receptors (IgNARs), in which the variable (V) domains recognize antigens with only a single immunoglobulin domain, akin to camelid heavy-chain V domains. The 1.45 angstrom resolution crystal structure of the type I IgNAR V domain in complex with hen egg-white lysozyme (HEL) reveals a minimal antigen-binding domain that contains only two of the three conventional complementarity-determining regions but still binds HEL with nanomolar affinity by means of a binding interface comparable in size to conventional antibodies.     

A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield

The HIV envelope (Env) protein gp120 is protected from antibody recognition by a dense glycan shield. However, several of the recently identified PGT broadly neutralizing antibodies appear to interact directly with the HIV glycan coat. Crystal structures of antigen-binding fragments (Fabs) PGT 127 and 128 with Man(9) at 1.65 and 1.29 angstrom resolution, respectively, and glycan binding data delineate a specific high mannose-binding site. Fab PGT 128 complexed with a fully glycosylated gp120 outer domain at 3.25 angstroms reveals that the antibody penetrates the glycan shield and recognizes two conserved glycans as well as a short β-strand segment of the gp120 V3 loop, accounting for its high binding affinity and broad specificity. Furthermore, our data suggest that the high neutralization potency of PGT 127 and 128 immunoglobulin Gs may be mediated by cross-linking Env trimers on the viral surface.     

Soil quality relationships with tree growth in exotic forests in New Zealand

Quantitative information on the relationships between site quality and plantation productivity (dominated by the exotic species Pinus radiata) is required to achieve goals for sustainable forest production. Soil quality is a key component of site quality. A nationwide study of soil quality measurements is reported for 35 representative forest sites, covering a wide range of climatic and edaphic conditions found throughout New Zealand's plantation forest estate, representing most of the soils used for plantation forestry in New Zealand. The objectives of the study were to find the most important soil properties that discriminated among eight New Zealand Soil Orders and determine relationships between Soil Orders and early tree growth rates for P. radiata and Cupressus lusitanica. Soil physical and chemical properties were measured to identify key soil indicators of soil quality related to tree productivity. Tree growth was measured after four years on small plots planted at very high stand density (40 000 stems ha⁻¹). A factorial design was used to examine the influence of three factors on tree productivity: two species, P. radiata D. Don (ectomycorrhizal) and C. lusitanica Miller (endomycorrhizal); with and without fertilizer; and low or high disturbance (soil compaction and/or topsoil scalping by machinery). Carbon content, Phosphorus (P) retention, and soil physical properties that index the degree of soil compactness were strongly correlated to Soil Order. These properties are similar to soil quality factors that correlated with tree growth. Discriminant analyses of soil quality parameters by Soil Order clustered soils based on P retention (phosphate absorption capacity), subsoil Carbon (C), and subsoil air capacity (volume % of voids at 10 kPa matric potential). Allophanic Soils and Podzols clustered (from plots of first versus second canonical variates) separately from the other Soil Orders, which were somewhat clustered on the second variate within a broad clustering on the first variate. Soil Orders were ranked for tree growth rates for both species: pumice Andisols > Inceptisols > tephric Andisols > Entisols > Ultisols > Spodosols (NZ classification: for P. radiata is Pumice > Brown > Pallic > Allophanic > Recent > Raw > Ultic > Podzol and for C. lusitanica Pumice > Pallic > Allophanic > Brown > Raw > Ultic > Recent > Podzol).     

Vernalization promotes flowering of a heat tolerant Calandrinia while long days replace vernalization for early flowering of Brunonia

The flowering responses of Brunonia australis (blue pincushion) and Calandrinia sp. to vernalization, photoperiod, temperature and plant age were investigated to provide a foundation for manipulating flowering in these potential potted plants. Plants were vernalized at 4.8 °C for 0, 3 or 6 weeks at the plant age of 1–4 or 8–14 leaves. Following vernalization, plants were grown at 25/10 or 35/20 °C (day/night) under short days (11 h, ambient daylight averaged 380 ± 44 μmol m⁻² s⁻¹) or long days (16 h) provided by an additional 5 h night break (21:00–2:00 h at <4.5 μmol m⁻² s⁻¹ from incandescent lamps), for 85 days. This is the first work to investigate flowering of these ornamental species. Both species showed enhanced flowering following vernalization and a quantitative requirement for long days. The reduction of the time until the first visible inflorescence (Brunonia) or flower (Calandrinia) buds by 8–13 days was affected by vernalization for 3 or 6 weeks, respectively. Long days were effective for reducing the time to first visible floral bud and increasing the number of inflorescence or flowers per plant for both species. For Brunonia, LDs replaced vernalization when applied to plants with 1–4 leaves. Raising temperature from 25/10 to 35/20 °C increased the number of flowers per plant of Calandrinia by 2–2.5-fold for plants with 1–4 or 8–14 leaves respectively.     

预防猪呼吸道疾病复合症的措施

兽医专家在哥本哈根举行的国际猪兽医协会大会上组织了一次专题研究会,讨论了猪呼吸道疾病复合症在全球范围内的发生情况。他们说,有关猪呼吸道疾病复合症的问题现在依然存在,而且不止是猪呼吸道疾病性复合症的病原体在各个不同国家中的差异问题。     

Involvement of antifungal compounds from rockmelon fruit rind (<Emphasis Type="Italic">Cucumis melo</Emphasis> L.) in resistance against the fruit rot pathogen <Emphasis Type="Italic">Fusarium oxysporum</Emphasis> f. sp. <Emphasis Type="Italic">melonis</Emphasis>.

Fusarium rot caused by Fusarium oxysporum f. sp. melonis, causes significant postharvest losses in rockmelon crops. Although latent infection is often present in the field, symptoms of the disease may not appear until fruit maturity. The susceptibility of different-aged rockmelon fruit cv. “Colorado” was determined by inoculating fruit at different stages of development with a spore suspension of F. oxysporum f. sp. melonis. Disease symptoms appeared first and were more severe in older fruit compared to younger fruit. Disease symptoms on fruit 35 DAA (Days After Anthesis) and 42 DAA appeared within 3 days of inoculation and rapidly covered the fruit within 5 days. In contrast, disease symptoms on fruit 7 DAA appeared 6 days after inoculation and grew slowly. Extraction of antifungal compounds without involving acid hydrolysis from 7 DAA fruit rind did not show antifungal activity on TLC plates. However, hydrolysis of the ethyl acetate fraction resulted in a strong fungal inhibitory zone on agar plates against colonies of F. oxysporum f. sp. melonis. Separation of the hydrolysed crude extracts on TLC plates indicated the presence of two distinct antifungal zones with R_f 0.36 and 0.13 in young fruit 7, 14 and 21 DAA. The area of fungal inhibition of compound R_f 0.36 was greater than that of R_f 0.13 on the TLC plate. Extracts from mature fruit of 35 and 42 DAA did not have detectable levels of antifungal compounds. The decrease in the susceptibility of rockmelon fruit during maturity may be correlated to a decrease in the antifungal compounds in the fruit with maturity.     

Pre-implantation exogenous progesterone and pregnancy in sheep. Ⅱ. Effects on fetalplacental development and nutrient transporters in late pregnancy

Background: Administration of progesterone(P4) to ewes during the first 9 to 12 days of pregnancy accelerates blastocyst development by day 12 of pregnancy, likely due to P4-induced up-regulation of key genes in uterine epithelia responsible for secretion and transport of components of histotroph into the uterine lumen. This study determined if acceleration of blastocyst development induced by exogenous P4 during the pre-implantation period affects fetal-placental development on day 125 of pregnancy. Suffolk ewes(n = 35) were mated to fertile rams and assigned randomly to receive daily intramuscular injections of either corn oil vehicle(CO, n = 18) or 25 mg progesterone in CO(P4, n = 17) for the first 8 days of pregnancy. All ewes were hysterectomized on day 125 of pregnancy and: 1) fetal and placental weights and measurements were recorded; 2) endometrial and placental tissues were analyzed for the expression of candidate mRNAs involved in nutrient transport and arginine metabolism; and 3) maternal plasma, fetal plasma, allantoic fluid, and amniotic fluid were analyzed for amino acids,agmatine, polyamines, glucose, and fructose.Results: Treatment of ewes with exogenous P4 did not alter fetal or placental growth, but increased amounts of aspartate and arginine in allantoic fluid and amniotic fluid, respectively. Ewes that received exogenous P4 had greater expression of mRNAs for SLC7 A1, SLC7 A2, SLC2 A1, AGMAT, and ODC1 in endometria, as well as SLC1 A4, SLC2 A5, SLC2 A8 and ODC1 in placentomes. In addition, AZIN2 protein was immunolocalized to uterine luminal and glandular epithelia in P4-treated ewes, whereas AZIN2 localized only to uterine luminal epithelia in CO-treated ewes.Conclusions: This study revealed that exogenous P4 administered in early pregnancy influenced expression of selected genes for nutrient transporters and the expression of a protein involved in polyamine synthesis on day 125 of pregnancy, suggesting a ‘programming' effect of P4 on gene expression that affected the composition of nutrients in fetal-placental fluids.