Gas-phase ionic reactions: dynamics and mechanism of nucleophilic displacements

Nucleophilic displacement reactions (the SN2 reaction) of ions in the gas phase are a prototypical reaction system that allows a study of dynamics, mechanisms, and structure-energy relations. This article reviews aspects of the kinetics (especially the applicability of statistical reaction rate theory), the relation of structure and reactivity, and the effects of small numbers of solvent molecules on the reaction and compares the behavior of the ionic reaction in the gas phase with that in solution.     

Cambrian burgess shale animals replicated in clay minerals

Although the evolutionary importance of the Burgess Shale is universally acknowledged, there is disagreement on the mode of preservation of the fossils after burial. Elemental mapping demonstrates that the relative abundance of elements varies between different anatomical features of the specimens. These differences reflect the compositions of the minerals that replicated the decaying organism, which were controlled by contrasts in tissue chemistry. Delicate morphological details are replicated in the elemental maps, showing that authigenic mineralization was fundamental to preserving these fossils, even though some organic remains are also present.     

Thalidomide pharmacokinetics in sheep

AIM: To determine the half life (T_1/2), time taken to reach maximum plasma concentration (T_max) and maximum plasma concentration (C_max) of thalidomide in sheep following I/V, oral and topical treatment with a single dose of thalidomide.

METHOD: Three groups of 4–6-month-old ram lambs were treated with thalidomide dissolved in dimethylsulphoxide (DMSO). The first group (n=10) was treated I/V with 100?mg thalidomide in 2?mL DMSO; the second group (n=8) received 400?mg thalidomide in 2?mL DMSO orally, and the third group (n=8) had 400?mg thalidomide in 4?mL DMSO applied topically. Plasma samples were collected up to 36 hours after treatment, snap-frozen at ?80°C and analysed for concentrations of thalidomide using high performance liquid chromatography.

RESULTS: Following I/V administration, T_1/2 was 5.0 (SEM 0.4) hours, volume of distribution was 3,372.0 (SEM 244.3) mL/kg and clearance was 487.1 (SEM 46.1) mL/hour.kg. Topical application of 400?mg thalidomide did not increase plasma concentrations. Following oral administration, thalidomide bioavailability was 89%, with T_1/2, T_max, and C_max being 7.2 (SEM 0.8) hours, 3.0 (SEM 0.4) hours and 1,767.3 (SEM 178.1) ng/mL, respectively.

CONCLUSION: Topical administration using DMSO as a solvent did not increase concentrations of thalidomide in plasma. The mean pharmacokinetic parameters determined following oral treatment with 400?mg of thalidomide were similar to those reported in humans receiving a single 400?mg oral dose (T_1/2 7.3 hours; T_max 4.3 hours and C_max 2,820?ng/mL). There is potential for thalidomide to be used as a model for the treatment of chronic inflammatory conditions in sheep, such as Johne's disease, where tumour necrosis factor alpha plays a pathogenic role.     

Orbital extraskeletal osteosarcoma following enucleation in a cat: a case report

Objective We present a unique case of a feline orbital extraskeletal osteosarcoma that developed 5 years post‐enucleation. History In 2002, an ophthalmologist enucleated the left eye of a 2‐year‐old neutered male DSH and submitted it to the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW). COPLOW diagnosed the left eye with feline diffuse iris melanoma. In June 2007, the cat presented to another veterinarian for moderate swelling of the enucleation site. Palpation suggested a firm mass along the lateral orbital rim and an exploratory orbitotomy revealed a cyst with a mass adhered to it and the ventrolateral orbital rim. The cyst and mass were excised by the veterinarian and submitted to COPLOW. COPLOW diagnosed the tissue as an orbital conjunctival inclusion cyst and an acquired orbital osteosarcoma. Conclusions Following the enucleation, retained conjunctival epithelium became embedded in the connective tissue of the orbit and caused a cyst to develop. The cyst wall consisted of a myofibroblastic collagen‐rich matrix and acted as a nidus of chronic irritation and tumor growth. This orbital osteosarcoma resembles feline vaccine‐associated sarcomas (VAS), feline post‐traumatic ocular sarcomas, and microchip‐associated sarcomas in terms of it histopathology and its hypothesized pathogenesis related to exposure to antigenic material such as implanted epithelium, lens protein, vaccine components, and microchips as foreign bodies.     

Bilateral Sertoli and Interstitial Cell Tumours in Abdominal Testes of a Goat with Polled Intersex Syndrome (PIS)

An 8‐year‐old, mixed breed, polled goat was presented for evaluation of male‐like behaviour. Clinical findings included clitoromegaly, a heavily muscled neck, pronounced beard, and erect dorsal guard hairs, which are phenotypic characteristics commonly observed in intersex animals. Transrectal ultrasonography revealed the presence of two abdominal masses caudolateral to the uterine horns. Serum concentration of estradiol was elevated. Genetic evaluation was compatible with polled intersex syndrome defined by an XX karyotype without a Y chromosome or SRY gene. Based on gross and histologic evaluation, the abdominal masses were determined to be intra‐abdominal testes, each of which was effaced by Sertoli cell and interstitial (Leydig) cell tumours. The Sertoli cell tumours (SCTs) represented two unique histologic patterns. Regardless of pattern, neoplastic Sertoli cells were consistently lipid laden and positive for vimentin. Interstitial cell tumours (ICTs) were negative for vimentin. Clinical and histopathologic findings suggest that prolonged exposure to steroids secreted by neoplastic Sertoli cells contributed to virilization. In addition, results from immunohistochemistry indicated that vimentin may be a valuable immunodiagnostic tool for differentiation between interstitial and Sertoli cell tumours in goats.     

Dermatoses caused by infestations of immature Ixodes spp. on dogs and cats in Sydney, Australia

Infestations of larval and nymphal Ixodes spp. were identified in 16 dogs and 16 cats from several small animal clinics in Sydney. Cases occurred in late summer or autumn, peaking in February, and were seasonally recurrent in some individuals. Clinical signs of infestation included a papular dermatitis and irritation or pruritus that ranged from severe to mild or absent. The distribution of tick attachment tended to be cranial and ventral, with the face, legs, axillae and ventrum the most commonly affected sites. The estimated number of ticks in each infestation varied from less than 10 to more than 100. Basic morphological examination of ticks collected from affected animals was performed by attending veterinarians using light microscopy, and larvae and nymphs belonging to the Ixodes genus were identified. Ticks collected from 17 animals and submitted to the Department of Medical Entomology, Westmead Hospital were putatively identified as I. trichosuri (57%) and I. holocyclus (25%) larvae. Histopathological samples of attachment sites collected from three dogs and one cat were characterised by ticks attached in well-demarcated invaginations of the skin ('tick craters') associated with variable epidermal and/or dermal necrosis, focal eosinophilic intraspinous pustules, mild to marked eosinophilic and neutrophilic, superficial to deep, dermal perivascular to interstitial inflammation, and moderate to marked superficial dermal oedema and red cell extravasation. A range of topical acaricidal preparations, including fipronil and synthetic pyrethroids, were used for treatment.