Summary The histological aspects of second‐intention healing were studied in 5 horses and 5 ponies. Biopsies were taken weekly from standardised wounds on the metatarsus and femoral biceps muscle of one horse and one pony. Sections were stained to enable cell counting and the detection of DNA synthesis, fibrin, smooth muscle actin (SMA), collagen, and bacteria. In the ponies, the number of polymorphonuclear leucocytes (PMNs) was high during the first 3 weeks and subsequently decreased rapidly. In the horses, the initial number of PMNs was lower, but remained persistently elevated during the evaluation period. PMNs were found mainly in the superficial zones. Significantly more fibrin was present in the wounds of the horses. No significant differences were observed in the number of fibroblasts, the amounts of SMA and collagen. However, myofibroblasts were significantly less regularly organised in the wounds of the horses, particularly in the metatarsal wounds. The mitotic activity of the epithelium was temporally reduced in week 3. The mitotic activity of the granulation tissue was initially high but declined rapidly from week 1 onwards, with the exception of the metatarsal wounds of the horses, in which mitotic activity remained significantly higher. Histology confirmed and explained the macroscopical differences in wound healing between horses and ponies by the strict organisation of the myofibroblasts and the more effective acute inflammation in the ponies. Stimulation of the organisation of myofibroblasts and improvement of the efficacy of the inflammatory response in horses may therefore result in better second‐intention wound healing in horses in clinical practice.

Summary Second‐intention healing of deep wounds was studied in 5 horses and 5 ponies. Standardised wounds were created on the distal limbs and hind quarters. Wounds on the metatarsi extended onto the metatarsal bone; the depth of the wounds in the femoral biceps muscle was 18 mm. The wound margins were marked by tattoos. Photographs were taken at weekly intervals to determine the wound area. The relative contribution of contraction and epithelialisation to wound closure was quantified by means of the tattoos. Swelling of the limbs was measured; and regularity and aspect of the granulation tissue were semi‐quantitatively scored. Second‐intention wound healing occurred significantly faster in ponies than in horses, and muscle wounds healed significantly faster than metatarsal wounds. These marked differences reflected the greater contribution of contraction to wound healing. Moreover, demarcation was seen earlier and a healthy granulation bed developed more rapidly in ponies, whereas in horses the granulation tissue remained irregular and purulent for longer. Healing of the metatarsal wounds of horses differed markedly from that of all other wounds: these wounds increased to almost twice their original size in the first 2 weeks, exuberant granulation tissue was persistent, epithelialisation started later, and contraction played a minor role in wound closure. Limb swelling was greater in horses than in ponies. Periosteal new bone formation was more extensive, and was active over a longer period in the metatarsal bones of horses than of ponies. From this study it is concluded that second‐intention healing of deep wounds occurs faster in ponies than in horses. This difference can be largely attributed to a more pronounced and faster wound contraction in ponies than in horses. Therefore, attempts to improve second‐intention wound healing in clinical practice should be directed at stimulation of wound contraction.

Since 1977, the WHO Model List of Essential Medicines (EML), published by WHO, has provided advice for Member States that struggle to decide which pharmaceutical technologies should be provided to patients within their public health systems. Originating from outside WHO, an incentive system has been put in place by various governments for the development of medicines for rare diseases ("orphan drugs"). With progress in pharmaceutical research (e.g. drugs targeted for narrower indications), these medicines will feature more often on future public health agendas. However, when current definitions for selecting essential medicines are applied strictly, orphan drugs cannot be part of the WHO Essential Medicines Programme, creating the risk that WHO may lose touch with this field. In our opinion WHO should explicitly include orphan drugs in its policy sphere by composing a complementary Orphan Medicines Model List as an addition to the EML. This complementary list of "rare essentials" could aid policy-makers and patients in, for example, emerging countries to improve access to these drugs and stimulate relevant policies. Furthermore, inconsistencies in the current EML with regard to medicines for rare diseases can be resolved. In this paper we propose selection criteria for an Orphan Medicines Model List that could form a departure point for future work towards an extensive WHO Orphan Medicines Programme.

Objectives Administration to rats of mood stabilizers approved for bipolar disorder (BD) downregulates markers of the brain arachidonic acid (AA, 20:4n-6) metabolic cascade, including phospholipase A2 (PLA2) and cyclooxygenase (COX) expression. We hypothesized that other agents that target the brain AA cascade, nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids, also would ameliorate BD symptoms. Methods Medication histories on subjects who had been prescribed lithium were collected from the Netherlands PHARMO Record Linkage System. Data were stratified according to drug classes that inhibit PLA2 and/or COX enzymes, and duration of use. Incidence density (ID) of medication events (dose increase or substance change) was used as a proxy for clinical worsening. ID ratios in patients with the inhibitors plus lithium were compared to ratios in patients using lithium alone. Results Low-dose acetylsalicylic acid (aspirin) significantly reduced the ID ratio of medication events, independent of use duration. The ID ratios of NSAIDs and glucocorticoids did not differ significantly from 1.0 if prescribed for ≥ 180 or ≥ 90 days, but exceeded 1.0 with shorter use. Selective COX-2 inhibitors had no significant effect and multiagent administration increased the ID ratio above 1.0. Conclusions Low-dose aspirin produced a statistically significant duration-independent reduction in the relative risk of clinical deterioration in subjects on lithium, whereas other NSAIDs and glucocorticoids did not. These tentative findings could be tested on larger databases containing detailed information about diagnosis and disease course, as well as by controlled clinical trials. (238 words)

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