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.     

Long-term study of aerobic bacteria of the genital tract in stud dogs.

The aerobic bacterial flora of the genital tract was characterized in 15 stud dogs in an 18-month study. The dogs represented 4 breeds and were from 3 kennels. Bacterial samples from the prepuce and semen were collected every month, except in connection with matings, when they were collected weekly (464 samples). The dogs that were included all mated at least once during the study. The mean pregnancy rate, litter size, and pup mortality for the bitches with which they had mated were all within normal limits. The most frequent bacteria isolated from the prepuce and semen were Pasteurella multocida, beta-hemolytic streptococci, and Escherichia coli. There was a tendency for breeds to differ in frequency of the most common bacterial species. Bacterial culture yielded no aerobic growth in 14.2% of the preputial samples and 69.8% of the semen samples. Bacteria were transferred between dog and bitch at mating. In this study of healthy breeding dogs, neither the fertility of the dog nor that of the bitch was affected by the bacteria transferred.     

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.     

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.     

Consistency of results from the Vettest 8008 clinical biochemistry analyser.

Findings are presented on the precision of a clinical biochemistry analyser designed specifically for veterinary use. Twenty biochemical analytes have been examined in detail for variation within and between runs. The results indicate that the analyser can provide high precision for all the analytes with the possible exception of calcium, and suggest that the instrument can be used with confidence in the practice laboratory to aid diagnosis and to monitor biochemical changes in animals receiving treatment.     

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)     

Bovine spongiform encephalopathy: epidemiological features 1985 to 1990.

Following the identification of bovine spongiform encephalopathy (BSE) in the British cattle population in 1986 epidemiological studies were launched. This paper provides an updated account of the epidemiological features of BSE from 1985, when the first cases, based on clinical histories, occurred, until 1990. The number of cases up to December 1989 represents an annual incidence of 3.9 confirmed cases per 1000 adult animals in Great Britain. Many more dairy herds were affected than beef suckler herds, a difference attributable to the difference in feeding practices between the two herd types. The geographical variation in incidence previously described has persisted with the highest incidence in the south and east of England. Other features of the epidemiology, including the low within-herd incidence, remained unaltered from the earlier findings. The results support the previously suggested hypothesis that the outbreak of BSE was due to the sudden exposure of the cattle population to a scrapie-like agent in 1981/82. There was no evidence of direct transmission between cattle during the period considered.     

Immunologic responses in healthy random-source cats fed N,N-dimethylglycine-supplemented diets.

The immunomodulatory capacities of N,N-dimethylglycine (DMG) were examined in random-source cats. Blood mononuclear leukocytes of healthy adult cats that had negative results to tests for FeLV and feline immunodeficiency virus were exposed in vitro to various concentrations of DMG (10 to 1,000 micrograms/ml) and were evaluated for proliferative responses to T- or B-cell phytomitogens. Although increased, mean lymphocyte blastogenic responses to phytolectins in DMG-treated cultures did not differ significantly from responses of untreated cultures. For in vivo studies, cats were given a solution containing either 100 mg of DMG or a control solution without DMG orally at 8 AM and 6 PM for 40 consecutive days. On post-treatment day 24 and 25, mean blastogenic responses to phytolectins in DMG-treated and control cats inoculated 10 days earlier with an inactivated feline virus vaccine were similar. Cats given DMG and inoculated twice in a 3-week interval with a commercial vaccine containing inactivated feline herpesvirus-1 and feline calicivirus had significantly (P = 0.045) lower virus neutralizing serum antibody titers against feline herpesvirus-1, compared with titers of control cats, whereas feline calicivirus titers were similar in both groups. On day 25, mean serum interferon activity, induced after IV inoculation of Newcastle disease virus, was significantly (P = 0.021) lower in the DMG-treated cats. Results of this study of DMG in healthy cats failed to demonstrate enhancement of either specific or nonspecific immunity.     

Blindness associated with toxoplasmosis in canaries.

Seven of 30 canaries in an aviary in New Zealand developed ophthalmic problems. Clinically, 5 birds had unilateral and 2 birds had bilateral lesions characterized by conjunctivitis, crusty exudates on eyelids, and collapse of the eyeball. Microscopic lesions in 12 of 14 eyes examined included inflammation of the choroid and retina, with osseous replacement of the globe in some. Numerous Toxoplasma gondii tachyzoites were seen in the detached retina and vitreous humor of acutely affected birds. The diagnosis of toxoplasmosis was confirmed by immunohistochemical staining with T gondii antiserum. Affected birds had encephalitis, and T gondii was localized in the brains of these by immunohistochemical examination and by use of bioassays in mice. Toxoplasmosis should be considered in differential diagnosis of ophthalmitis in canaries.