Fractionated oral dosing and its effect on cyclophosphamide pharmacokinetics in dogs with high-grade multicentric lymphoma

Cyclophosphamide (CP) is an alkylating agent commonly included in multi-drug treatment protocols for canine cancer. As a prodrug, CP requires hepatic metabolism for activation to the intermediate compound 4-hydroxycyclophosphamide (4-OHCP) which then spontaneously forms alkylating phosphoramide mustard. CP is frequently administered in a fractionated manner, with the total dose given over multiple days. CP is reported to cause auto-induction of metabolism in humans, with faster CP clearance and relatively increased 4-OHCP formation following fractionated versus bolus dosing, however canine pharmacokinetic studies of CP dose fractionation are lacking. The study objective was to evaluate the pharmacokinetics of fractionated oral CP dosing at a dose of 200–250 mg/m² over 3 to 4 days in a prospectively identified population of cancer-bearing dogs. Plasma concentrations of CP and 4-OHCP were measured by ultra-high performance liquid chromatography tandem-mass spectrometry in eight dogs following the first and last doses to assess for auto-induction of CP metabolism. No significant difference in the rate of CP elimination between first and last doses were detected (0.73 ± 0.46 vs. 1.22 ± 0.5 h⁻¹; p = .125). Additionally, no significant difference in dose-normalized 4-OHCP exposure was identified between first and last doses (5.9 ± 2.1 vs. 7.9 ± 6.4 h × ng/ml; p = .936). These results suggest that fractionated dosing may not increase exposure to the active metabolite of CP in dogs as it does in humans. As such, standard bolus dosing and fractionated dosing may be equivalent in terms of bio-activation of CP in dogs administered a dose of 200–250 mg/m².     

Zaluzanin D: a fungistatic sesquiterpene from Vernonia arborea

Zaluzanin D, a sesquiterpene lactone has been isolated from the aerial parts of Vernonia arborea as a major constituent (0.04%). Antifungal activity of zaluzanin D has been studied against six plant-pathogenic fungi.     

Do the tropical freshwater fishes feed on aquatic fungi?

Consumption and processing of allochthonous plant litter by fishes is more common in tropical than temperate streams and rivers. Therefore, aquatic hyphomycetes in water (filtration), leaf litter (bubble chamber incubation), and fecal pellets (direct observation and inoculation to sterile leaf litter) of three dominant fishes belonging to the family Cyprinidae (Aplocheilus lineatus, Puntius filamentosus, and Rasbora daniconius) in two locations of the River Kali of the Western Ghats, India, were evaluated during postmonsoon season. Spores of 14 and 9 species of aquatic hyphomycetes were recovered on filtering water samples of Kaiga stream and Kadra dam with equal number of spores (32 spores · 100 mL⁻¹) and high Shannon diversity in Kaiga stream. In a bubble chamber incubation of leaf litter, 16 and 9 species were recovered from Kaiga stream and Kadra dam with high spore output (1122 versus 324 spores per mg dry mass) and high Shannon diversity in Kaiga stream. Both direct and indirect methods of examination of fecal pellets of fishes revealed more species in Kaiga stream than Kadra dam (4–7 versus 1–4 species). The spore release in leaf litter incubated with fecal pellets ranged from 2.3 to 98 spores·mg⁻¹·d⁻¹ with the highest Aplocheilus lineatus in Kaiga stream; while in Kadra dam, it was from 0.02 to 22.9 spores·mg⁻¹·d⁻¹ with the highest in Puntius filamentosus. The Shannon diversity of aquatic hyphomycetes was high in fecal pellets of Aplocheilus lineatus of Kaiga stream and Rasbora daniconius of Kadra dam. The top-ranked five species of aquatic hyphomycetes differed in water, leaf litter, and fish fecal pellets; however, Triscelophorus konajensis was common for all. All five top-ranked species of aquatic hyphomycetes in feces produced multicelled spores; thus, they were likely to have a better chance of viability through gut passage than single-celled spores. Preferential feeding, fungi in gut and feces, and survival and dissemination of spores by invertebrates and fishes with reference to aquatic hyphomycetes were discussed.     

Progress in breeding for resistance to Ug99 and other races of the stem rust fungus in CIMMYT wheat germplasm

Races belonging to the Ug99 (TTKSK) lineage of the wheat stem rust fungus, carrying complex virulence combinations, and their migration to countries in Africa, Middle East and Asia continue to pose a significant threat to global wheat production. The rapid spread of additional races, e.g., TKTTF or the Digalu lineage, in several countries causing localized epidemics reminds us of the vulnerability of wheat germplasm to stem rust disease, a formidable foe referenced as early as biblical times. A global rust monitoring system reflecting increased surveillance efforts has identified 13 races within the Ug99 lineage in 13 countries and unrelated lineages are emerging, spreading and posing serious threats to wheat production. Race TKTTF has caused localized epidemics in Ethiopia and its variants have been recently implicated in stem rust outbreaks in Europe. Concerted research efforts have resulted in the identification of several new resistance genes and gene combinations for use in breeding. Combining multiple adult plant resistance (APR) genes in high-yielding backgrounds and discovery of new quantitative trait loci conferring stem rust resistance has progressed in the recent years, enhancing the durability of resistance. Effective gene stewardship and new generation breeding materials and cultivars that combine multiple race-specific or minor to intermediate effect APR genes, complemented by active surveillance and monitoring, have helped to limit major epidemics and increase grain yield potential in key target environments.     

Nutritional evaluation of tender pods of <Emphasis Type="Italic">Canavalia maritima</Emphasis> of coastal sand dunes

This study has been performed to evaluate the nutritional, antinutritional and protein qualities of tender pods of Canavalia maritima, the coastal sand dune wild legume of southwest India. The proximal features, minerals, amino acids, fatty acids, antinutritional and protein qualities of fresh and pressure-cooked tender pods have been assessed. The crude protein was comparable to seeds of many edible legumes. Cooking significantly elevated the carbohydrates and calorific value of tender pods (P < 0.05), while crude fiber was significantly decreased (P < 0.05). Minerals of fresh pods did not drain too much on cooking and K, Mg, Zn and Mn in fresh as well as cooked pods were comparable or higher than the NRC-NAS recommended pattern. Although cooking decreased the essential amino acids, threonine, valine, isoleucine, phenylalanine and lysine in cooked pods were equivalent or higher than the FAO-WHO-UNU recommended pattern. The palmitoleic acid in fresh pods and eicosenoic acid in cooked pods were relatively high. Similarly, the essential fatty acids, linolenic acid and linoleic acid were confined to fresh and cooked pods respectively. The fresh pods were devoid of tannins and trypsin inhibitors. The total phenolics and hemagglutinin activity decreased substantially in cooked pods. The diet of pressure-cooked pods showed improvement of in vivo protein quality, elevation of growth parameters and positive nitrogen balance in rats. Overall, the pressurecooking of tender pods of C. maritima improved the nutritional qualities by lowering the hemagglutinin activity.     

Rapid Determination of Mercury in Plant and Soil Samples Using Inductively Coupled Plasma Atomic Emission Spectroscopy, a Comparative Study

The objectives of this study were to simplify sample preparation and validate mercury detection in soil and plant samples using inductively coupled plasma atomic emission spectroscopy (ICP-AES). A set of mercury contaminated and mercury free soil and plant samples were digested and analyzed by ICP-AES, inductively coupled plasma mass spectrometry (ICP-MS), and cold vapor atomic absorption spectroscopy (CVAAS). Results show that mercury measurements in soil and plant samples using ICP-AES were in agreement with those analyzed using ICP-MS and CVAAS. The concentrations of mercury in soils and plant tissues determined by ICP-AES were 92.2% and 90.5% of those determined by CVAAS and ICP-MS, respectively. Digestion of soil samples with 4 M HNO₃ and direct measurement by ICP-AES without reduction of Hg²⁺ to Hg⁰ gave a reasonable and acceptable recovery (92%) for determining Hg in soils. We conclude that ICP-AES with optimized conditions (addition of gold chloride, extension of washing time, linear working range, and selection of wavelength – 194 nm) resulted in reliable detection of mercury in environmental samples.     

Evaluation of Groundwater Quality Characteristics near Two Waste Sites in Ibadan and Lagos,Nigeria

Two industrial and highly populated cities namely Ibadan and Lagos, both located in Southwestern Nigeria have urban migrationproblems and resource limitations. As a result, the development of residential areas near waste sites and the indiscriminate dumping of municipal waste are common in both cities. Orita-Aperin and Oworonsoki neighborhoods in Ibadan and Lagos,respectively, both located near a waste site were studied. The two areas relied on the wells as sources of drinking water hence poor drinking water quality may have health consequences. A totalof 51 ground-water samples (30 wells in Ibadan and 21 wells in Lagos) were monitored seasonally for two years in Ibadan and a year in Lagos. Results from this study revealed that some of theground-water quality constituents determined exceeded the World Health Organization (WHO) standards for drinking water irrespective of source of pollution. Some of the ground-water samples were poor in quality in terms of pH, conductivity, totaldissolved solids, chloride, nitrate, ammonia, COD, Al, Cd, Cr, Fe, Pb, Ni and total coliforms recorded. Thus, ground-water fromsome of these private wells requires further purification to ensure its fitness for human consumption.F-test, one-way parametric analysis of variance (ANOVA), Mann-Whitney `T' test and Kruskal-Wallis H-test applied to upgradient and downgradient concentrations suggest impact ofthe waste sites on ground-water quality. The Mann-Whitney testonly suggests that the downgradient values of Fe (Ibadan: dryseason (1), sulfate (Ibadan: rainy season (2) and pH (Lagos: dry season (2) were significant at 5% level of significance. For Ibadan wells, the Kruskal-Wallis test showed that variances ofspecific conductivity, dissolved solids, and chloride for Ibadanupgradient and downgradient values were unequal. Also variances of specific conductivity and dissolved solids for upgradient anddowngradient values in Lagos were unequal at 5% level of significance. Three downgradient wells in Lagos and four downgradient wells in Ibadan had significant impact due to leachate migration into drinking wells.     

Harnessing Plant Growth Promoting Rhizobacteria Beyond Nature: A Review

Root-associated plant growth promoting rhizobacteria (PGPR) interact with the plant roots and influence plant health and soil fertility. Plant growth promoting rhizobacteria play an important role in plant growth by exerting various mechanisms such as biological nitrogen fixation, growth hormone production, phosphate solubilization, siderophore production, hydrolytic enzyme production, antagonistic activity against fungal pathogens etc. Hence, these are employed as inoculants for biofertilizer and biocontrol activities. This review summarizes various mechanisms of PGPR and their potential for use as inoculants. It shows that their use is a worthwhile approach for exploring disease management in conjunction with other strategies.     

Long incomplete longitudinal fractures of the third metacarpal and metatarsal bone in horses

Five horses with long incomplete longitudinal fractures of the third metacarpal bone and three horses with similar fractures of the third metatarsal bone were examined. In three of the metacarpal fractures a long incomplete fissure extended proximomedially, in association with the more common lateral condylar fracture of the third metacarpal bone, and in the other two cases the fracture originated from the medial aspect of the distal articular surface. In the three horses with fractures of the third metatarsal bone the fractures had a consistent spiral configuration.     

Evaluation of the effects of histone deacetylase inhibitors on cells from canine cancer cell lines

OBJECTIVE: To determine whether exposure of canine cancer cells to histone deacetylase (HDAC) inhibitors S(+)-N-hydroxy-4-(3-methyl-2-phenyl-butyrylamino)benzamide (OSU-HDAC42) or suberoylanilide hydroxamic acid (SAHA) results in increased histone acetylation and decreased cell viability and whether any changes in viability involve induction of apoptosis or alterations in progression of the cell cycle. Sample POPULATION: 9 canine cancer cell lines. PROCEDURES: Cells from 9 canine cancer cell lines were treated with dimethyl sulfoxide vehicle, OSU-HDAC42, or SAHA, then assays of cell viability were performed. Histone acetylation was assessed by use of western blot analysis. Apoptosis was assessed via ELISA to detect fragmentation of cytoplasmic nucleosomal DNA and western blot analysis to detect cleavage of caspase 3. Cell cycle analysis was performed by use of propidium iodide staining and flow cytometry. RESULTS-Concentrations of OSU-HDAC42 and SAHA required to achieve 50% inhibition of cell viability (IC(50)) were reached in cells of 6 and 4 canine cancer cell lines, respectively, and ranged from approximately 0.4 to 1.3 microM for OSU-HDAC42 and 0.6 to 4.8 microM for SAHA. Cells from T-cell lymphoma, mast cell tumor, osteosarcoma, and histiocytic sarcoma lines were most sensitive to HDAC inhibition, with IC(50)s of < 1 microM for OSU-HDAC42 and < 5 microM for SAHA. Induction of apoptosis was indicated via cleavage of caspase 3 and increases in cytoplasmic nucleosomes and the subG(1) cell population. CONCLUSIONS AND CLINICAL RELEVANCE: Micromolar concentrations of HDAC inhibitors OSU-HDAC42 and SAHA induced histone acetylation, cytotoxicity, and apoptosis in canine cancer cells. In general, OSU-HDAC42 was more potent than SAHA.