ART26.12, a novel fatty acid-binding protein 5 inhibitor, shows efficacy in multiple preclinical neuropathy models.

BACKGROUND: Painful neuropathy is a pathological condition caused by numerous factors including diabetes, chemotherapy or cancer. ART26.12 is a novel fatty acid-binding protein 5 inhibitor, which our group showed could prevent and treat persistent pain in a preclinical model of oxaliplatin-induced peripheral neuropathy. METHODS: In the current study, the efficacy of orally dosed ART26.12 was tested in multiple neuropathy models of different aetiology. Paw withdrawal threshold to von Frey monofilaments and latency to escape a cold plate were used as measurements of mechanical and cold sensitivity. RESULTS: ART26.12 (25 and 50 mg/kg BID), dosed prior to the induction of paclitaxel-induced peripheral neuropathy (PIPN), reversed mechanical allodynia induced by paclitaxel in both male and female rats, and ART26.12 (50 mg/kg BID) prevented the induction of PIPN in female rats. ART26.12 (50 mg/kg BID) also had a protective effect on body weight in the PIPN model. ART26.12 (25 and 100 mg/kg BID) reversed mechanical allodynia when treating established streptozotocin-induced diabetic neuropathy in male rats. In a model of breast cancer-induced bone pain in female rats, ART26.12 (100 mg/kg BID) reversed mechanical allodynia within 1 h of dosing. In the same model, ART26.12 (25 mg/kg BID) reversed mechanical allodynia from day 4 of treatment. CONCLUSION: Overall, these preclinical data suggest that ART26.12 is a safe and efficacious therapeutic drug for continued development towards the prevention and treatment of peripheral neuropathy. SIGNIFICANCE STATEMENT: This work now shows that ART26.12, a novel and selective inhibitor of FABP5, can prevent and treat multiple preclinical models of peripheral neuropathy. Given its excellent safety profile, further work is warranted to develop ART26.12 as a potential therapeutic tool for pain management.

Organochlorines in Pleuronectidae: comparison between three tissues of three species inhabiting the Northwest Atlantic.

Muscle, liver, and gonad from three species of flatfish, turbot, American plaice, and yellowtail flounder collected in the Northwest Atlantic were analyzed for a variety of organochlorine contaminants. Female flounder and plaice had lower concentrations of organochlorines than males, in all tissues. Comparing values to those previously obtained for Atlantic cod showed that concentrations in liver, the organ most often used in biomarker studies, followed the order: cod > turbot > plaice > flounder and correlated with lipid content. Muscle concentrations, which are important from a consumers perspective, followed the order: turbot > plaice > flounder > cod and were also correlated with lipids. The concentration of contaminants in gonads, the organ that informs on the future of a species were nearly undetectable. Cluster analyses demonstrated that the environmental behaviour of these contaminants can be subdivided into groups, consistent with their known chemical origin. Of the series of total and specific polychlorinated dibenzo-p-dioxins and furans studied, only tetrachlorodibenzofuran was present in most tissues.

A study of the relation between eating disorder and death concern.

The relationship between eating disorder and various components of death orientation (fear, anxiety, acceptance and concern) was examined, taking into account the level of depression in patient samples as well as elements of religiosity. The results were not able to support more than a very modest relationship between eating disorder and death orientation. Eating disorder patients could not be distinguished from other clinical controls, nor did anorexia nervosa patients differ from other eating disorder patients in this respect. Beck and Beck [20] depression scores were higher in the non eating disordered clinical sample than in the eating disorder group, and death concern was shown to be related to the severity of depression. Religiosity did not appear important when indices of religiosity were considered, but did emerge as an important factor in the "free information" provided by participants.

Organochlorines including polychlorinated biphenyls in muscle, liver, and ovaries of cod, Gadus morhua.

Twenty-three specific organochlorine contaminants and polychlorinated biphenyls (PCBs), measured as three Aroclor standards were analyzed in muscle, liver, and ovaries of cod, Gadus morhua, collected in the Northwest Atlantic. In general, contaminants were undetectable in muscle tissue, while concentrations were 10 times lower in ovaries than liver (wet weight). Comparison of results to other locations indicated a similarity between the ratio of the concentrations of p,p'-DDE, p,p'-DDD and p,p'-DDT, in liver of cod from the northern North Sea and from the Northwest Atlantic, although with lower levels in the present study. The ratio of alpha-HCH and gamma-HCH was between that of the central and northern North Sea. Similar ratios tend to indicate similar residence times in the atmosphere, from source to sampling area. Comparison of sigma PCB and sigma DDT in the liver of cod from various geographical locations showed the following general trend in concentrations: Arctic, Northwest Atlantic, West Atlantic, Norway < North Baltic, Nova Scotia, North Sea < South Baltic. It was observed that if the liver concentration of one compound was low (high), there was a tendency for all compounds to be low (high). Cluster analysis of organochlorines in liver pointed to the presence of four basic clusters, which could reflect similar physical chemical properties within a group. Concentrations of organochlorines in ovaries were below levels expected to affect egg and larval viability.

Death anxiety in Japan and Australia.

This study compared death anxiety ratings as measured by the Templer Death Anxiety Scale (Templer, 1970) in 121 Japanese and 139 Australian subjects. Japanese subjects had significantly higher death anxiety scores than their Australian counterparts. Australian women scored significantly higher than Australian men, but no sex differences were found in the Japanese sample. A slight but statistically significant positive correlation was found between age and death anxiety scores. This study contradicted other research that indicated that Eastern cultural attitudes mitigated anxiety about death. These findings are discussed in relation to the complex relationship between culture and death anxiety as well as in relation to problems inherent in our current conception of death anxiety.

Primary health care as an educational process: a model and a freirean perspective.

This is a discussion that attempts to open up to reflection some of the deeper aspects of Primary Health Care. A model originally derived to assist reflection on philosophies of education is drawn on and illustrated with the very pertinent ideas of Paulo Freire. The article aims at assisting that deeper level of deliberation which is especially important to a comprehensively conceived Primary Health Care.