Sirarjenje v planinah v Kamniško-Savinjskih Alpah v luči arheoloških najdb in zgodovinskih virov

Razprava obravnava začetke izdelave sira v Kamniško-Savinjskih Alpah. Analizirane so arheološke najdbe (lončena torila in posode) in pisni zgodovinski viri (urbarji). Odprto je ostalo vprašanje, ali so v antiki v planinah tudi sirili. Gornjegrajski urbar iz leta 1426 in reformirani urbar zgornjekamniškega gospostva iz leta 1571 dokazujeta sirastvo v visokem srednjem veku. *** The paper looks at the beginnings of cheese making in the Kamnik and the Savinja Alps. Analyzed are archaeological artefacts (cheese moulds, clay vessels for milk) and written historical sources (land registers). The question whether in antiquity the shepherds who were grazing cattle on mountain pastures also processed cheese remains unanswered. Land registers, for instance the 1426 land register of Gornji grad and the reformed land register of the Upper Kamnik seigneury from 1571, contain more data on the cheese making tradition in the High Middle Ages

New, highly efficient formulation of diclofenac for the topical, transdermal administration in ultradeformable drug carriers, Transfersomes

AbstractTransfenac, a lotion-like formulation of diclofenac, is described. It consists of pharmaceutically acceptable ingredients and mediates the agent transport through intact skin and into the target tissues. Therapeutically meaningful drug concentrations in the target tissue are reached even when the administered drug dose in Transfenac is below 0.5 mg/kg body weight. Ultradeformable agent carriers, called Transfersomes, form the basis of Transfenac. These Transfersomes are proposed to cross the skin spontaneously under the influence of transepidermal water activity gradient (see [Biochim. Biophys. Acta 1104 (1992) 226]). Diclofenac association with ultradeformable carriers permits it to have a longer effect and to reach 10-times higher concentrations in the tissues under the skin in comparison with the drug from a commercial hydrogel. For example, Transfenac achieves intramuscular agent concentrations between 0.5 and 2 μg/g and 2 and 20 μg/g at t=12 h, depending on the tissue depth, when it is administered in the dose range 0.25–2 mg/kg of rat body weight. A much higher drug concentration in a hydrogel (1.25–10 mg/kg body weight) creates the drug level of only <0.5 μg/g in the muscle. The drug concentration in the rat patella for these two types of formulation is between 1 μg/g and 5 μg/g or 0.4 μg/g, respectively. The relative advantage of diclofenac delivery by means of ultradeformable carriers increases with the treated muscle thickness and with decreasing drug dose, as seen in mice, rats and pigs; this can be explained by assuming that the drug associated with carriers is cleared less efficiently by the dermal capillary plexus. In pigs it suffices to use 0.3 mg of diclofenac in highly deformable vesicles per kg body weight, spread over an area of 25 cm2, to ensure therapeutic drug concentration in a 5-cm thick muscle specimen, collected under the agent application site. When the drug is used in a hydrogel at 8 times higher dose, the average intramuscular concentration is at least three times lower and subtherapeutic. This suggests that diclofenac in Transfersomes has the potential to replace combined oral/topical diclofenac administration in humans