1. Two neuronal growth factors, nerve growth factor (NGF) and neurotrophin 3 (NT3), have been studied for their action on the developing and mature sympathetic nervous system. 2. Antibodies to each factor have proved useful as reagents for the detection and quantification of NGF and NT3. They have also proved valuable in uncovering the functional roles of each factor by their ability to neutralize the endogenous molecules. 3. Nerve growth factor acts on postnatal neurons to control neurotransmission, connectivity and survival. Like NGF, NT3 is synthesized by effector tissues and is retrogradely transported by post-ganglionic neurons to prevent cell death. However, the two factors have been shown to have quite distinct functions in mature neurons, indicating the existence of different signalling pathways. This differential action extends to secondary influences on satellite glia. 4. Pathological consequences result from excessive growth factor synthesis leading, in the hypertensive rat, to hyperinnervation and elevated blood pressure. Satellite glial cell synthesis of the factors and their receptors following peripheral nerve damage appears to be responsible for the establishment of inappropriate neuronal connections between sympathetic nerve terminals and sensory somata. 5. It is concluded that these potent factors control, by both coincident and independent mechanisms, sympathetic neuronal function throughout the life of the animal.

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Multiple sclerosis is an inflammatory and demyelinating disease of the central nervous system which mainly affects young adults. To overcome wide spectrum troublesome symptoms of multiple sclerosis which affects the quality of life both in patients and their families, new drugs and remedies have been examined and offered. The preclinical beneficial effects of different medicines have mostly been examined in an animal model of multiple sclerosis called experimental allergic encephalomyelitis (EAE). In this study we have tested a traditionally used natural (herbal-marine) product called MS(14) in EAE mice. EAE mice were fed with MS(14) containing diet (30%) on the immunization day and monitored for 20 days. The results show that while clinical scores and therefore severity of the disease was progressive in normal-fed EAE mice, the disease was slowed down in MS(14)-fed EAE mice. Moreover, while there were moderate to severe neuropathological changes in normal fed mice, milder changes were seen in MS(14) fed mice.

Differentiation therapy is attracting increasing interest in cancer as it can be more specific than conventional chemotherapy approaches, and it has offered new treatment options for some cancer types, such as treating acute promyelocytic leukaemia (APL) by retinoic acid. However, there is a pressing need to identify additional molecules which act in this way, both in leukaemia and other cancer types. In this work, we hence developed a novel transcriptional drug repositioning approach, based on both bioinformatics and cheminformatics components, that enables selecting such compounds in a more informed manner. We have validated the approach for leukaemia cells, and retrospectively retinoic acid was successfully identified using our method. Prospectively, the anti-parasitic compound fenbendazole was tested in leukaemia cells, and we were able to show that it can induce the differentiation of leukaemia cells to granulocytes in low concentrations of 0.1 μM and within as short a time period as 3 days. This work hence provides a systematic and validated approach for identifying small molecules for differentiation therapy in cancer.