Verrucosamide,a Cytotoxic 1,4-Thiazepane-Containing Thiodepsipeptide from a Marine-Derived Actinomycete

A new cytotoxic thiodepsipeptide, verrucosamide (1), was isolated along with the known, related cyclic peptide thiocoraline, from the extract of a marine-derived actinomycete, a Verrucosispora sp., our strain CNX-026. The new peptide, which is composed of two rare seven-membered 1,4-thiazepane rings, was elucidated by a combination of spectral methods and the absolute configuration was determined by a single X-ray diffraction study. Verrucosamide (1) showed moderate cytotoxicity and selectivity in the NCI 60 cell line bioassay. The most susceptible cell lines were MDA-MB-468 breast carcinoma with an LD₅₀ of 1.26 µM, and COLO 205 colon adenocarcinoma with an LD₅₀ of 1.4 µM. Also isolated along with verrucosamide were three small 3-hydroxy(alkoxy)-quinaldic acid derivatives that appear to be products of the same biosynthetic pathway.     

Clinical response of nasal adenocarcinoma to cisplatin chemotherapy in 11 dogs.

In 11 dogs with nasal adenocarcinoma, IV treatment with 2 to 8 cycles of cisplatin at a dosage of 60 mg/m2 of body surface, given at 3-week intervals, resulted in a survival time of 8 to 128 weeks (mean, 32.7 weeks; median, 20 weeks). Radiography revealed complete remission in 2 dogs and partial remission in 1 dog, for an overall response rate of 27%. Clinical problems such as nasal discharge (n = 11), sneezing (n = 6), and epistaxis (n = 4) resolved in 1 to 2 weeks in all dogs after beginning chemotherapy.     

Immunodeficiency associated with lymphosarcoma in a horse.

Immune system dysfunction and immunoglobulin deficiency was diagnosed in a 2-year-old horse with disseminated lymphosarcoma. Prolonged (35 days) parenteral nutrition was delivered to support the horse during a period in which immune function studies could be performed. Correction of nutritional compromise by use of parenteral nutrition did not correct the immunoglobulin deficiency, and results of lymphocyte phenotype testing did not indicate abnormal proportions of leukocytes. Lymphoblast transformation studies were suggestive of a circulating immunosuppressive factor in the horse's serum. Normal cell function was detected when the cells were stimulated in precolostral equine serum.     

Effect of a supply of raw or extruded rapeseeds on digestion in dairy cows.

The influence of extruded oilseeds on total tract digestibility and ruminal digestion in dairy cows was studied in three cows fed a hay-concentrate (60.5/39.5; 3.7% fatty acids in diet on DM basis) control diet (C) or the same diet supplemented with raw (R) or extruded (ER) rapeseeds (8.0% fatty acids in diet DM). The experimental design was a 3 x 3 Latin square design. Compared with diet C, diets containing rapeseed decreased ruminal OM digestibility (9.5%, P less than .10) and increased (P less than .05) the proportion of propionate in ruminal fluid VFA. Extrusion had no effect on DM and OM total tract digestibilities and increased (P less than .10) N digestion. Microbial N flow at the duodenum was calculated taking into account solid-adherent bacteria (SAB) and liquid-associated bacteria (LAB). Duodenal flows of total, SAB, and LAB of OM and N did not change with diet. Extrusion of the rapeseeds did not modify (P less than .10) the proportion of bacterial N at the duodenum and had no effect on crude fiber digestibility. This trial demonstrates that rapeseeds in hay-based diets can be fed at levels of up to 14% of the diet without adversely affecting crude fiber digestibility.     

Cryptococcal osteomyelitis in a dog

Osteomyelitis caused by Cryptococcus neoformans was diagnosed in a three-year-old male Irish wolfhound. The case details and radiological findings of radiolucency and periosteal reaction of the left third metatarsal bone had lead to an initial diagnosis of a malignant bone tumour. Biopsy revealed a fungal granuloma and culture identified the causal organism. A four month course of ketaconazole was instigated and the lameness resolved. Twelve months after the end of treatment there was no recurrence of the problem.     

Factors affecting skim milk progesterone assay results.

Five studies were performed to determine factors affecting progesterone concentration in skim milk. Results of the first study indicated that progesterone concentration was higher in skim milk of samples kept 16 hours in an ice bath (0 C) than of those left at room temperature (21 C). In the second study, this temperature effect was found to be reversible, with skim milk progesterone concentration increasing when whole milk samples were cooled prior to centrifugation. In the third study, [3H]-labeled progesterone was used to determine the relationship between fat content of foremilk (the first milk obtained from the teats), midmilk (milk obtained midway through milking), and strippings (milk obtained immediately after milking machines have been removed) samples and temperature (4 C and 21 C) on the percentage of progesterone in the skim milk fraction. The relationship between percentage of butterfat and percentage of progesterone in skim milk was linear when the log of these variables was used for calculations. In the fourth study, assayable progesterone in the skim milk fraction of foremilk, midmilk, and strippings was affected by temperature. In the fifth study, a multiple-regression procedure was used to determine the amount of variation in percentage of radioactive progesterone in the skim milk fraction. Independent variables (whole milk butterfat and temperature of incubation [1, 3, 13, 22, 37, and 50 C]) and the natural log of each variable, were entered into a stepwise multiple-regression analysis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative virulence of Haemophilus parasuis serovars 1 to 7 in guinea pigs.

Reference strains for Haemophilus parasuis serovars 1 to 7 were examined for virulence by inoculation of guinea pigs. Guinea pig response to intraperitoneal inoculation was similar for the 7 reference strains. However, apparent differences in virulence were detected after intratracheal inoculation. Cells of the references strains for serovars 1 and 5 were most invasive, causing moribundity or death at higher doses and a persistent septicemia at lower doses. Haemophilus parasuis could be isolated from respiratory and systemic sites; purulent bronchopneumonia, pericarditis, and pleuritis were apparent in infected guinea pigs. Inoculation of cells of the reference strains for serovars 2 and 6 also resulted in bronchopneumonia and moribundity or death in some guinea pigs; however, reisolation of H parasuis and microscopic lesions at necropsy were less pronounced than those observed with serovars 1 and 5. Inoculation of cells of serovars 3, 4 and 7 induced only transient clinical signs and minimal evidence of H parasuis infection at necropsy. The data from intratracheal inoculation of guinea pigs are similar to data from other investigations in swine, indicating differences in the pathogenic potential of H parasuis strains. Thus, guinea pigs may be useful as a laboratory animal model for examining cellular factors associated with virulence and immunogenicity of H parasuis.     

Ultrastructural observations on autolytic changes of atrial specific granules in pig heart.

The progressive autolytic changes of atrial specific granules (ASGS) up to 24 hours after death were studied electron microscopically. Tissue samples taken from the left auricular myocardium of four pig hearts at 0, 0.5, 1.5, 3.5, 6, 12 and 24 hours post mortem were fixed for 24 hours by immersion in 2.5 per cent cacodylate buffered glutaraldehyde (pH 7.4). Two pig hearts were kept at 20 degrees C and two at 4 degrees C. Although typical autolytic changes were seen in many organelles, no remarkable modifications in aspect, distribution, content and diameter of ASGS were observed in all samples. The results of this study indicate that ASGS are not morphologically affected by the autolytic processes, at least during the first 24 hours. Hence, the electron microscopic evaluation of ASGS does not need a particular fixation method such as perfusion. This may eliminate technical problems when slaughterhouse material is used.