An analysis of astrocytic cell lines with different abilities to promote axon growth

The adult mammalian central nervous system (CNS) lacks the capacity to support axonal regeneration. There is increasing evidence to suggest that astrocytes, the major glial population in the CNS, may possess both axon-growth promoting and axon-growth inhibitory properties and the latter may contribute to the poor regenerative capacity of the CNS. In order to examine the molecular differences between axon-growth permissive and axon-growth inhibitory astrocytes, a panel of astrocyte cell lines exhibiting a range of axon-growth promoting properties was generated and analysed. No clear correlation was found between the axon-growth promoting properties of these astrocyte cell lines with: (i) the expression of known neurite-outgrowth promoting molecules such as laminin, fibronectin andN-cadherin; (ii) the expression of known inhibitory molecules such tenascin and chondroitin sulphate proteoglycan; (iii) plasminogen activator and plasminogen activator inhibitor activity; and (iv) growth cone collapsing activity. EM studies on aggregates formed from astrocyte cell lines, however, revealed the presence of an abundance of extracellular matrix material associated with the more inhibitory astrocyte cell lines. When matrix deposited by astrocyte cell lines was assessed for axon-growth promoting activity, matrix from permissive lines was found to be a good substrate, whereas matrix from the inhibitory astrocyte lines was a poor substrate for neuritic growth. Our findings, taken together, suggest that the functional differences between the permissive and the inhibitory astrocyte cell lines reside largely with the ECM.     

Evidence for the ventral origin of oligodendrocyte precursors in the rat spinal cord

The neuroepithelial cells of the mammalian neural tube are thought to give rise to all classes of differentiated neurons and macroglial cells in the adult CNS. In most cases, the regulation and timing of commitment of neuroepithelial cells to specific differentiative pathways are unknown. It has been proposed that in developing spinal cord, the macroglial cells--astrocytes and oligodendrocytes--arise either by the direct transformation of radial glial cells in the developing cord or, alternatively, by the differentiation of distinct precursor cells which migrate to presumptive white matter from the region of the central canal during development. In this study, the timing of oligodendrocyte differentiation in different levels of the spinal cord and the capacity of specific regions of the spinal cord to give rise to oligodendrocytes at various ages was tested in vitro. At embryonic day 14, all complete segments, as well as all ventral regions along the rostral-caudal axis of the spinal cord, have the capacity for oligodendrogenesis. By contrast, dorsal regions of the thoracic and lumbar spinal cord do not develop the capacity for oligodendrogenesis until later in development. The capacity of dorsal rat spinal cord to give rise to oligodendrocytes appears to be associated with the ventral-to-dorsal migration of oligodendrocyte precursors. These observations suggest that commitment to an oligodendrocyte differentiative pathway appears to occur in a distinct population of ventrally located glial precursors in the embryonic rat spinal cord.     

Singapore Neonatal Resuscitation Guidelines 2021

Neonatal resuscitation is a coordinated, team-based series of timed sequential steps that focuses on a transitional physiology to improve perinatal and neonatal outcomes. The practice of neonatal resuscitation has evolved over time and continues to be shaped by emerging evidence as well as key opinions. We present the revised Neonatal Resuscitation Guidelines for Singapore 2021. The recommendations from the International Liaison Committee on Resuscitation Neonatal Task Force Consensus on Science and Treatment Recommendations (2020) and guidelines from the American Heart Association and European Resuscitation Council were compared with existing guidelines. The recommendations of the Neonatal Subgroup of the Singapore Resuscitation and First Aid Council were derived after the work group discussed and appraised the current available evidence and their applicability to local clinical practice.     

Laparoscopic obesity surgery in an Asian Institute: A 10‐year prospective study with review of literature

Objective: Obesity surgery is the most effective treatment for morbid obesity and leads to dramatic improvement in related co‐morbidities. The aim of this study was to present the long‐term results of a prospective trial studying the efficacy of laparoscopic obesity surgery in a group of oriental patients. Method: From April 1998 to March 2009, 2385 patients who underwent obesity surgery in a single bariatric center in Asia were recruited. Various procedures have been adopted so far, including laparoscopic vertical banded gastric partition in 652 patients (27.3%), laparoscopic gastric bypass (LGB) in 1228 patients (51.5%), laparoscopic adjustable gastric banding in 226 patients (9.5%), laparoscopic sleeve gastrectomy in 128 patients (5.4%), gastric balloon in 68 patients (2.8%) and laparoscopic revision surgery in 83 patients (3.5%). We evaluated the clinical data and effect of obesity surgery on different procedures. Results: Overall, the major complication rate and mortality were 1.5% and 0.12%. There was an increase of surgical risk in laparoscopic sleeve gastrectomy and laparoscopic revision surgery patients. The mean total weight loss for the population was 28.1%, 33.9%, 21.3% 18.7% and 17.4% at 1, 3, 5, 7 and 9 years after surgery, respectively. LGB had a better weight loss (30.1%) than that of the restrictive‐type procedures (20.9%) at 5 years after surgery. After surgery, most of the obesity‐associated co‐morbidities were resolved or improved in these patients. Conclusion: Laparoscopic obesity surgery resulted in significant and sustained weight loss in morbidly obese Asian patients with resolution of associated co‐morbidities. LGB had a better result in weight reduction than other restrictive procedures.     

Apamin binding sites in human C6 cell line and their accessibility to monoclonal antibodies

Apamin, a 18-amino acid bee venom toxic peptide specifically blocks a class of Ca(2+)-activated K+ channels. i) Mono 125I-iodoapamin binds to receptor sites in a human neuroglial cell line (C6 line) but not in human cell lines from pancreatic (RIN5F line) and colonic origin (HT29 line). ii) Receptor-bound apamin is still accessible to a large molecule since some anti-apamin monoclonal antibodies recognize apamin when bound to its receptor, both in intact cells of the human C6 glioma line and in rat brain synaptosomal membranes.     

Irinotecan treatment and senescence failure promote the emergence of more transformed and invasive cells that depend on anti-apoptotic Mcl-1

Induction of senescence by chemotherapy was initially characterized as a suppressive response that prevents tumor cell proliferation. However, in response to treatment, it is not really known how cells can survive senescence and how irreversible this pathway is. In this study, we analyzed cell escape in response to irinotecan, a first line treatment used in colorectal cancer that induced senescence. We detected subpopulations of cells that adapted to chemotherapy and resumed proliferation. Survival led to the emergence of more transformed cells that induced tumor formation in mice and grew in low adhesion conditions. A significant amount of viable polyploid cells was also generated following irinotecan failure. Markers such as lgr5, CD44, CD133 and ALDH were downregulated in persistent clones, indicating that survival was not associated with an increase in cancer initiating cells. Importantly, malignant cells which resisted senescence relied on survival pathways induced by Mcl-1 signaling and to a lesser extent by Bcl-xL. Depletion of Mcl-1 increased irinotecan efficiency, induced the death of polyploid cells, prevented cell emergence and inhibited growth in low-adhesion conditions. We therefore propose that Mcl-1 targeting should be considered in the future to reduce senescence escape and to improve the treatment of irinotecan-refractory colorectal cancers.