1 The nuclear factor-kB (NF-kB) is a transcription factor which plays a pivotal role in the induction of genes involved in physiological processes as well as in the response to injury and in¯ammation. Dithiocarbamates are antioxidants which are potent inhibitors of NF-kB. 2 We postulated that pyrrolidine dithiocarbamate (PDTC) would attenuate in¯ammation. In the present study we investigate the e ects of PDTC in animal models of acute and chronic in¯ammation (carrageenan-induced pleurisy and collagen-induced arthritis). 3 We report here for the ®rst time that PDTC (given at 100, 30 or 10 mg kg 71 i.p. in the pleurisy model or at 10 mg kg 71 i.p. every 48 h in the arthritis model) exerts potent anti-in¯ammatory e ects (e.g. signi®cant reduction of (A) pleural exudate formation, (B) polymorphonuclear cell in®ltration, (C) lipid peroxidation, (D) inducible nitric oxide synthase (iNOS) activity and nitric oxide production (E) plasma and pleural exudates levels of interleukin-1b and tumour necrosis factor-a, (F) histological injury and (G) delayed development of clinical indicators). 4 Furthermore, PDTC reduced immunohistochemical evidence of (A) formation of nitrotyrosine, (B) activation of poly (ADP-ribose) polymerase (PARP), (C) expression of iNOS and (D) expression of cyclo-oxygenase-2 (COX-2) in the lungs of carrageenan-treated mice and in the joints from collagen-treated mice. 5 Additionally, Western blotting and immunohistochemical analysis of lung tissue revealed that PDTC prevented degradation of IKB-a and translocation of NF-kB from the cytoplasm into the nucleus. 6 Taken together, our results clearly demonstrate that prevention of the activation of NF-kB by PDTC reduces the development of acute and chronic in¯ammation. Therefore, inhibition of NF-kB may represent a novel approach for the therapy of in¯ammation.

There is limited evidence that inhibition of the activity of the protease calpain I reduces inflammation. Here we investigate the effects of calpain inhibitor I in animal models of acute and chronic inflammation (carrageenan-induced pleurisy and collagen-induced arthritis). We report here for the first time that calpain inhibitor I (given at 5, 10, or 20 mg/kg i. It is now widely accepted that the formation of pro-inflammatory cytokines [eg, tumor ecrosis factor-␣ (TNF␣), interleukin IL)Ϫ1, IL-6,or IL-8], the expression on endothelium and neutrophils of adhesion molecules (eg, VCAM-1, ICAM-1), and the overproduction of vasoactive mediators [eg, nitric oxide (NO) by inducible NO synthase (iNOS) or eicosanoids by cyclooxygenase-2 (COX-2)] play important roles in the pathophysiology of inflammation. The expression of inducible genes leading to the formation of these proteins relies on transcription factors, which are controlled by (other) inducible genes and, hence, require de novo protein synthesis or alternatively by so-called primary transcription factors. Among the latter, nuclear factor B (NF-B) has received a considerable amount of attention because of its unique mechanism of activation and its active role in cytoplasmic/nuclear signaling, and its rapid response to pathogenic stimulation of NF-B plays a central role in the regulation of many genes responsible for the generation of mediators or proteins in inflammation. These include the genes for TNF␣, IL-1, IL-6, IL-8, VCAM-1, ICAM-1, iNOS, and COX-2, to name but a few.

Oslerus rostratus syn. Anafilaroides rostratus (Strongylida: Filaroididae) is a metastrongyloid transmitted by snails, which localizes in peri-bronchial tissues and in the lung parenchyma of wild as well as domestic cats. In Europe, this nematode has been reported only on two occasions, being diagnosed in cats from Majorca Island and in northern Spain. Here, we describe a case of O. rostratus infection in a necropsied 4-year-old cat in Sicily (southern Italy). At the inspection of lungs, slender and greyish nematodes (four females and two males) were found embedded in the peri-bronchial tissues and in the bronchial walls. Parasites were morphological and molecularly identified as O. rostratus, with their 18S sequences being identical among them and showing a high homology (99%) with those available in public databases. At the histology, nematodes were encapsulated in a pseudo-cystic formation surrounded by an interstitial inflammatory process and fibrous tissue. Lung lesions were mainly represented by peri-luminal fibrosis, hyperplasia and hypertrophy of the bronchial mucosa and glands, respectively. This first record of O. rostratus infection from Italy indicates that this parasite should be included in the differential diagnosis of feline of lungworm infection.

1 The aim of the present study was to investigate the e ects of cloricromene, a coumarine derivative, in rats subjected to collagen-induced arthritis. 2 Collagen-induced arthritis (CIA) was induced in Lewis rats by an intradermal injection of 100 ml of the emulsion (containing 100 mg of bovine type II collagen) (CII) and complete Freund's adjuvant (CFA) at the base of the tail. On day 21, a second injection of CII in CFA was administered. 3 Lewis rats developed an erosive hind paw arthritis when immunized with CII in CFA. Macroscopic clinical evidence of CIA ®rst appeared as peri-articular erythema and oedema in the hind paws. The incidence of CIA was 100% by day 27 in the CII challenged rats and the severity of CIA progressed over a 35-day period with radiographic evaluation revealing focal resorption of bone together with osteophyte formation in the tibiotarsal joint and soft tissue swelling. 4 The histopathology of CIA included erosion of the cartilage at the joint margins. Treatment of rats with cloricromene (10 mg kg 71 i.p. daily) starting at the onset of arthritis (day 23), delayed the development of the clinical signs at days 24 ± 35 and improved histological status in the knee and paw. 5 Immunohistochemical analysis for iNOS, COX-2, nitrotyrosine and for poly (ADP-ribose) synthetase (PARS) revealed a positive staining in in¯amed joints from collagen-treated rats. The degree of staining for iNOS, COX-2, nitrotyrosine and PARS were markedly reduced in tissue sections obtained from collagen-treated rats, which had received cloricromene. 6 Radiographic signs of protection against bone resorption and osteophyte formation were present in the joints of cloricromene-treated rat. 7 This study provides the ®rst evidence that cloricromene, a coumarine derivative, attenuates the degree of chronic in¯ammation and tissue damage associated with collagen-induced arthritis in the rat.

This study is the first to provide evidence that tempol, a small molecule that permeates biologic membranes and scavenges reactive oxygen species, attenuates the degree of chronic inflammation and tissue damage associated with CIA in the rat.