L-lactate reduces ischemic white matter injury and modulates HCA1 oligodendrocyte expression in an in vivo mouse model of focal ischemia

L-lactate is a metabolite that is oxidized preferentially to glucose under conditions of high metabolic stress. The discovery and localization of the lactate receptor HCA1 in various brain regions suggests that lactate is additionally an important signaling molecule in the brain. Lactate is neuroprotective in various ischemia paradigms, reduces axonal injury in vitro and is avidly utilized by oligodendrocytes (OLs). The protective potential of L-lactate to reduce white matter (WM) injury in a mouse stroke model was investigated.N/

Elevated of nitric oxide during hypoglycemia cause structural and functional injury to callosal white matter axons in the rodent brain

Nitric oxide (NO) is a free radical that can act both as a signalling molecule and a neurotoxin. Previous literature suggest that it is involved in multiple brain pathologies. The main aim of this study was to investigate the role of NO in conduction block and structural axonal injury during and following glucose deprivation (GD).N/

Effect of an intronic variant within Zinc finger protein 384 gene on pre-mRNA splicing in a Maltese family with osteoporosis

INTRODUCTION: Osteoporosis is a skeletal disease with a strong genetic basis. A study on an extended Maltese family with a highly penetrant form of osteoporosis, revealed the presence of the rs146089604 variant (c.686+32G>A) in intron 7 of the Zinc finger protein 384 (ZNF384) gene, predicted to affect pre-messenger RNA (mRNA) splicing. The aim of this study was to assess the functional effect of the variant using an exon-trapping vector transfected in three human cell types.METHODS: The target DNA region harbouring G or A allele was inserted in the p.SPL3 vector, creating mini-gene constructs that were transfected in human kidney-derived cells (HEK-293) and two human osteoblasts-derived cells (SaOS-2 and h-FOB). Extracted mRNA was converted into complementary DNA (cDNA), amplified by PCR and sequenced to determine the transcript size and identify any splicing variants.RESULTS: Mini-gene construct with the alternative A allele lead to exon 8 and part of intron 8 to be retained, both of which were spliced off in the presence of the G allele. These results were observed for constructs transfected in the osteoblasts-derived cell lines. In HEK-293 cells, no difference in transcript size was seen for the G or A allele, suggesting different splicing mechanisms.CONCLUSION: Observations may indicate that the ZNF384 rs146089604 could be a causal variant contributing to osteoporosis. ZNF384 transactivates type I collagen and matrix metalloproteinases, and suppresses bone morphogenic protein (BMP) and Wnt signalling resulting in reduced bone volume and strength. Thus, impaired ZNF384 splicing could alter the protein’s function affecting bone homeostasis.peer-reviewe

10th Malta Medical School Conference : conference abstract book

Once again, it is my privilege and pleasure as Chairman of the 10th Malta Medical School Conference to extend a very warm welcome to all the international and local participants. This triennial conference has become a regular, major academic activity feature in the Malta Medical School calendar and is now in its 10th edition. Since its inception in 1988, it has evolved and its success and popularity have increased due to the tireless work and dedication of many people. The importance of this medical conference, in our local scenario, is once again evident with over 800 abstracts submitted. This certainly confirms the extent and quality of ongoing academic research taking place locally in the various disciplines, as well as the growing popularity of this triennial event. It is the responsibility of our profession towards our patients to keep abreast of new developments in the various medical fields, and this conference will certainly contribute towards this. The Scientific Committee, most ably chaired by Professor P. Schembri Wismayer, has produced a vibrant and exciting scientific programme, which I am sure, will generate a lot of interest. This programme will follow the general format of the previous conferences in that it will consist of a compilation of multi-disciplinary sessions and plenary lectures. Five parallel sessions will be running concurrently throughout the whole three-day programme to be able to give adequate exposure to all our participants. Two poster sessions will also be organised. This is my third time as Chairman of the Malta Medical School Conference and once again, I was extremely fortunate to have a dedicated team of colleagues who worked assiduously together. Their enthusiasm and fervent support has made this event possible. I would like to take this opportunity to thank them all for their excellent work and support throughout. Invaluable help was provided by Ms Christianne Mizzi and Ms Zvetlana Zerafa, the Conference Secretaries, the staff at the Medical School, competently lead by Ms Doris Mangion and various other individuals who supported and helped us with organising this event. For this I thank them all. I must also thank all the Pharmaceutical Exhibitors and Conference Sponsors without whose financial support this event would not have been possible. A particular word of thanks goes to Professor Godfrey LaFerla, the Dean of the Faculty of Medicine and Surgery for his continuous support and encouragement and for entrusting me with the organisation of this important conference. Last but certainly not least, I would like to thank you, the participants, who will be participating in this event. May I wish you all an enjoyable and successful conference. [excerpt from the Foreword]N/