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.     

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.     

Hematopoietic cell regulation by Rac1 and Rac2 guanosine triphosphatases

The Rho guanosine triphosphatases (GTPases) Rac1 and Rac2 are critical signaling regulators in mammalian cells. The deletion of both Rac1 and Rac2 murine alleles leads to a massive egress of hematopoietic stem/progenitor cells (HSC/Ps) into the blood from the marrow, whereas Rac1-/- but not Rac2-/- HSC/Ps fail to engraft in the bone marrow of irradiated recipient mice. In contrast, Rac2, but not Rac1, regulates superoxide production and directed migration in neutrophils, and in each cell type, the two GTPases play distinct roles in actin organization, cell survival, and proliferation. Thus, Rac1 and Rac2 regulate unique aspects of hematopoietic development and function.     

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.     

New icetexane diterpenes with intestinal α-glucosidase inhibitory and free-radical scavenging activity isolated from Premna tomentosa roots

New icetexane diterpenes (1-2); 8, 11, 13-icetexatriene-10-hydroxy, 11, 12, 16-tri acetoxyl (1) and 8, 11, 13-icetexatriene-7, 10, 11-dihydroxy-12, 13-dihydrofuran (2) along with six known compounds namely acetoxy syranzaldehyde (3), syranzaldehyde (4), coniferaldehyde (5), lupeol (6), betulin (7), and 4-(4-methoxy phenyl)-2-butanone (8) were isolated from the roots of Premna tomentosa. The structures of compounds 1 and 2 were established by detailed spectral analysis using UV, IR, ¹H NMR, ¹³C NMR, 1D, 2D and Mass. The newly isolated compounds were screened for rat intestinal α-glucosidase inhibitory and free radical (DPPH) scavenging potentiality. The new icetexane diterpenes (1, 2) and compound 3 were found to have significant α-glucosidase inhibitory and also free radical scavenging (DPPH) activities.     

Non-mycorrhizal fungal endophytes in two orchids of Kaiga forest (Western Ghats), India

We used standard isolation protocols to explore the endophytic fungal communities in three tissue types of two dominant orchids (Bulbophyllum neilgherrense and Vanda testacea) of the Kaiga forest ofthe Western Ghats. We surface sterilized and assessed 90 segments ofeach orchid for the occurrence and diversity of endophytic fungal taxa.The 118 fungal isolates were obtained from root, bulb and leaves of B.neilgherrense, consisting of 17 anamorphic taxa (range, 10 15 taxa) with 1.3 fungal taxa per segment (range, 1.2 1.4 taxa). Four taxa (Aspergillus flavus, A. niger, Penicillium sp. and morpho sp. 1) belonged to the coregroup (11.1% 32.2%). The relative abundance of A. flavus and morpho sp.1 was more than 10%. A total of 130 fungal isolates from roots, stems and leaves of V. testacea yielded 20 anamorphic taxa (range, 11 15 taxa)with 1.4 fungal taxa per segment (range, 1.4 1.5 taxa). Aspergillus flavus,A. niger, A. ochraceus, Gliocladium viride, Penicillium sp. and morphosp. 1 belonged to the core group. Relative abundance exceeded 10% for A. flavus, A. niger, and morpho sp. 1. The Simpson and Shannon diversity indices were higher in leaf than root or bulb/stem of both orchids.Jaccard’s similarity coefficient was higher between root and leaf in both orchids (56.3% 60%) than between other pairs. Our study revealed thatthe endophytic fungal assemblage and diversity of B. neilgherrense and V.testacea of Kaiga forest of the Western Ghats were relatively similar between orchids and their tissues.