Epipolythiodiketopiperazines from the Marine Derived Fungus Dichotomomyces cejpii with NF-κB Inhibitory Potential

The Ascomycota Dichotomomyces cejpii was isolated from the marine sponge Callyspongia cf. C. flammea. A new gliotoxin derivative, 6-acetylmonodethiogliotoxin (1) was obtained from fungal extracts. Compounds 2 and 3, methylthio-gliotoxin derivatives were formerly only known as semi-synthetic compounds and are here described as natural products. Additionally the polyketide heveadride (4) was isolated. Compounds 1, 2 and 4 dose-dependently down-regulated TNFα-induced NF-κB activity in human chronic myeloid leukemia cells with IC_50s of 38.5 ± 1.2 µM, 65.7 ± 2.0 µM and 82.7 ± 11.3 µM, respectively. The molecular mechanism was studied with the most potent compound 1 and results indicate downstream inhibitory effects targeting binding of NF-κB to DNA. Compound 1 thus demonstrates potential of epimonothiodiketopiperazine-derived compounds for the development of NF-κB inhibitors.     

Genotoxic activity of dichlorvos,trichlorfon and dichloroacetaldehyde

Two structurally related organophosphorous insecticides, dichlorvos and trichlorfon, and their main metabolite dichloroacetaldehyde, were assayed for their ability to induce DNA repair, detected as unscheduled DNA synthesis in human epithelial-like cell (EUE) cultures in vitro. A dose-response relationship was found for treatment with the two pesticides, but negative results were obtained with dichloroacetaldehyde. Tests for induction of gene mutation, as ouabain resistance in Chinese hamster cells (V79), failed to show any mutagenic activity by these compounds.     

Use of latissimus dorsi and abdominal external oblique muscle for reconstruction of a thoracic wall defect in a cat with feline osteochondromatosis

A 4-year-old, male castrated European shorthair cat was presented with a firm mass palpable on the right caudal rib cage. Lateral and ventrodorsal radiographs of the thorax revealed a 4x3x2cm large, expansile and radiodense mass originating from the distal part of the 13th rib. After removal of the tumour, which was histopathologically confirmed as feline osteochondromatosis, the diaphragm, omentum, external abdominal oblique and latissimus dorsi muscles were used to reconstruct the defect. Feline osteochondromatosis is induced by retroviruses, eg, feline leukaemia virus, for which the cat tested positive. The tumour was removed for palliative reasons, because such tumours have the tendency to transform into osteosarcomas. Six months after the surgical excision the cat showed no clinical signs of reoccurrence.     

Sertoli cell tumors associated with feminizing syndrome and spermatic cord torsion in two cryptorchid dogs

The association of cryptorchidism, functional Sertoli cell tumors, and spermatic cord torsion has been rarely reported in the literature. Two dogs were admitted for bilateral skin alopecia and weight loss. Both animals were cryptorchid and displayed a pendulous preputial sheath, prostate hypertrophy, and increased levels of circulating oestrogen. Transabdominal palpation and ultrasonography revealed the presence of neoplastic retained gonads. During surgery, spermatic cord torsion was also detected in the enlarged neoplastic testes of both dogs. Histologic examination confirmed the presence of Sertoli cell tumors that were primarily responsible for the feminizing syndrome. Complete remission of all symptoms occurred within 3 months after orchiectomy.