Commercial preparations of essences of sage, hyssop, thuja, and cedar have caused human intoxication in eight cases, from which tonico-clonic convulsions were the major symptom. The experimental study of the toxic properties of commercialized essential oils of sage and hyssop has revealed that their convulsant action was of central nervous system origin in unanesthetized rats, as proven by electrocortical records. The toxicity of the hyssop oil seems to be more powerful than that of sage, since the dose limit from which the cortical events are only subclinical is 0.08 g/kg for hyssop oil and 0.3 g/kg for sage oil. Above 0.13 g/kg for hyssop oil and 0.50 g/kg for sage oil, the convulsions appeared and became lethal above 1.25 g/kg with hyssop oil and 3.2 g/kg with sage oil. The daily repeated injection of subclinical doses revealed the cumulative toxic effect of hyssop oil, since the same low dose induced electrocortical clonic seizures. The toxicity of each oil appeared to be related to the presence of terpenic ketones, camphor in sage commercial oil, camphor and thujone in sage Dalmatian oil, thujone in thuja and cedar oils, and pinocamphone in hyssop oil. The convulsant properties of camphor are well known. The neurotoxicity of thujone and pinocamphone is demonstrated in rats for the first time.

The field of regenerative medicine offers the potential to significantly impact a wide spectrum of healthcare issues, from diabetes to cardiovascular disease. In particular, the design of tailored biomaterials, which possess properties desired for their particular application, and the development of superior implant environments, which seek to meet the nutritional needs of the tissue, have yielded promising tissue engineering prototypes. In this commentary, we examine the novel approaches researchers have made in customized biomaterials and promoting angiogenesis that have led to significant advancements in recent years.

The dark-like (dal) mutant mouse has a pleiotropic phenotype that includes dark dorsal hairs and reproductive degeneration. Their pigmentation phenotype is similar to Attractin (Atrn) mutants, which also develop vacuoles throughout the brain. In further characterizing the testicular degeneration of dal mutant males, we found that they had reduced serum testosterone and developed vacuoles in their testes. Genetic crosses placed dal upstream of the melanocortin 1 receptor (Mc1r) and downstream of agouti, although dal suppressed the effect of agouti on pigmentation but not body weight. Atrn(mg-3J) and dal showed additive effects on pigmentation, testicular vacuolation, and spongiform neurodegeneration, but transgenic overexpression of Attractin-like-1 (Atrnl1), which compensates for loss of ATRN, did not rescue dal mutant phenotypes. Our results suggest dal and Atrn function in the same pathway and that identification of the dal gene will provide insight into molecular mechanisms of vacuolation in multiple cell types.

This work identifies dark-like mice as a model of prolidase deficiency that will be valuable for studying the role of proline metabolism in normal physiology and disease processes, and suggests that integrin signaling may regulate the onset of hypertrophic cardiac growth.