Psychiatrists' attitude towards the use of clozapine in the treatment of refractory schizophrenia: A nationwide survey.

OBJECTIVES: Clozapine is the most effective treatment for refractory schizophrenia, yet it remains underused in clinical practice. The current study examined the awareness, familiarity and attitude of a nationwide sample of Israeli psychiatrists regarding the use of clozapine. METHODS: Data were collected using questionnaires, completed by 295 psychiatrists. Participants were asked to score questions regarding clozapine procedures; familiarity with guidelines, drug properties, prescription and attitude towards specialized clozapine resources. RESULTS: About half (53.3%) of the psychiatrists reported initiating treatment with clozapine according to the guidelines, whereas 33% reported that they administered clozapine only after three or more unsuccessful antipsychotic treatments. Surprisingly, availability of specialized resources for clozapine treatment (such as clozapine clinics) was associated with delayed initiation of clozapine treatment, and a lower rate of clozapine administration. Barriers to clozapine use included concerns about patient adherence, side effects and partial compliance with the required blood monitoring. CONCLUSIONS: Delaying or avoiding clozapine treatment to potentially eligible patients, despite familiarity with the drug efficacy and treatment guidelines, is a major mental health concern. However, executive allocation of resources to support the use of clozapine may be ineffective in promoting clozapine use.

Topical Erythropoietin Treatment Accelerates the Healing of Cutaneous Burn Wounds in Diabetic Pigs Through an Aquaporin-3-Dependent Mechanism.

We have previously reported that the topical application of erythropoietin (EPO) to cutaneous wounds in rats and mice with experimentally induced diabetes accelerates their healing by stimulating angiogenesis, reepithelialization, and collagen deposition, and by suppressing the inflammatory response and apoptosis. Aquaporins (AQPs) are integral membrane proteins whose function is to regulate intracellular fluid hemostasis by enabling the transport of water and glycerol. AQP3 is the AQP that is expressed in the skin where it facilitates cell migration and proliferation and re-epithelialization during wound healing. In this report, we provide the results of an investigation that examined the contribution of AQP3 to the mechanism of EPO action on the healing of burn wounds in the skin of pigs with experimentally induced type 1 diabetes. We found that topical EPO treatment of the burns accelerated their healing through an AQP3-dependent mechanism that activates angiogenesis, triggers collagen and hyaluronic acid synthesis and the formation of the extracellular matrix (ECM), and stimulates reepithelialization by keratinocytes. We also found that incorporating fibronectin, a crucial constituent of the ECM, into the topical EPO-containing gel, can potentiate the accelerating action of EPO on the healing of the burn injury.

Fibronectin potentiates topical erythropoietin-induced wound repair in diabetic mice.

Diabetes mellitus disrupts all phases of the wound repair cascade and leads to development of chronic wounds. We previously showed that topical erythropoietin (EPO) can promote wound repair in diabetic rats. Fibronectin (FN) has a critical role throughout the process of wound healing, yet it is deficient in wound tissues of diabetic patients. Therefore, we investigated the effect of topical treatment of both EPO and FN (EPO/FN) on wound repair in diabetic mice. Full-thickness excisional skin wounds in diabetic and nondiabetic mice were treated with a cream containing vehicle, EPO, FN, or EPO/FN. We assessed the rate of wound closure, angiogenesis, apoptosis, and expression of inflammatory cytokines, endothelial nitric oxide synthase (eNOS) and ß1-integrin, in the wound tissues. We also investigated the effect of EPO, FN, and EPO/FN on human dermal microvascular endothelial cells and fibroblasts cultured on fibrin-coated plates, or in high glucose concentrations. EPO/FN treatment significantly increased the rate of wound closure and this effect was associated with increased angiogenesis, increased eNOS and ß1-integrin expression, and reduced expression of inflammatory cytokines and apoptosis. Our findings show that EPO and FN have an additive effect on wound repair in diabetic mice.

Selective autoantibody production against CCL3 is associated with human type 1 diabetes mellitus and serves as a novel biomarker for its diagnosis.

We have recently demonstrated that patients suffering from chronic autoimmune diseases develop an autoantibody response against key mediators that participate in the initiation and progression of these diseases. In this paper, we show that patients with type 1 diabetes mellitus (T1DM), but not those suffering from several other inflammatory autoimmune diseases, display a selective autoantibody titer to a single CC chemokine named CCL3. From the diagnostic point we show that this response could be used as a biomarker for diagnosis of T1DM, a disease that is currently diagnosed by autoantibodies to competitive anti-insulin Abs, islet cell Abs, and glutamic acid decarboxylase Abs. We show that our currently suggested biomarker is more reliable than each of the above alone, including diagnosis of T1DM at its preclinical stage, and could therefore be used as a novel way for diagnosis of T1DM. These Abs were found to be neutralizing Abs. It is possible, though hard to prove, that these Abs participate in the natural regulation of the human disease. Hence, it has previously been shown by others that selective neutralization of CCL3 suppresses T1DM in NOD mice. Theses results together with ours suggest CCL3 as a preferential target for therapy of T1DM.