Astrocytes constitute the largest population of cells in the central nervous system, constituting approximately 90% of human parenchymal cells. Astrocytes are highly responsive to injury, undergoing rapid hyperplasia and hypertrophy. Astrocytes act as physical and biochemical barriers to axonal regeneration by forming glial scars along ischemic lesions and producing axonal growth-inhibitory proteoglycans. Administration of MSCs significantly attenuates the glial scar in the ischemic boundary and reduces expression of inhibitory proteins, such as Nogo. Analysis of single-cell astrocytes isolated from the ischemic boundary by laser capture microdissection reveals that administration of MSCs dramatically down regulates neurocan, an axonal growth-inhibitory proteoglycan. Coculture of MSCs with astrocytes also substantially reduces neurocan expression in astrocytes activated by oxygen glucose deprivation. These findings suggest that injected MSCs reduce physical and biochemical barriers of astrocytes, which also contribute to axonal and neurite outgrowth.
Virtually all vertebrates have an oxytocin-like nonapeptide hormone that supports reproductive functions and a vasopressin-like nonapeptide hormone involved in water regulation. The two genes are always located close to each other (less than 15,000 bases apart) on the same chromosome and are transcribed in opposite directions. It is thought that the two genes resulted from a gene duplication event; the ancestral gene is estimated to be about 500 million years old and is found in cyclostomes (modern members of the Agnatha).
Mouse bone marrow macrophage (BMMs) of 5-week-old female ICR mice (Charles River Laboratories, Seoul, South Korea) were used as previously described . Animals were maintained in accordance with the National Institute of Toxicological Research of the Korea Food and Drug Administration guideline for the humane care and use of laboratory animals Institutional Animal Care and Use Committee (IACUC) approval was obtained from Kyung Hee University (Seoul, Korea). Briefly, bone marrow of tibiae and femurs of mice were flushed with α-MEM. After removing erythrocytes with hypotonic buffer, cells were cultured in α-MEM containing 10% FBS for 24 h and adherent cells were discarded. Non-adherent bone marrow cells were transferred onto 100-mm non-coated petri dishes at 5×106 cells per dish and cultured in the presence of M-CSF (30 ng/ml) for 3 days. Condition medium (CM) was obtained from HPDLCs treated with 200 μM H2O2 or Tβ4 (0.5, 1 and 5 μg/mL) for 2 days. To evaluate the osteoclastogenic activity of CM from HPDLCs, we added the CM mixture (60% CM plus 40% fresh α-MEM without M-CSF or RANKL) or rh-Tβ4 to pre-osteoclast-stage cells and further cultured the cells for up to 5 days to achieve mature osteoclast differentiation BMMs (1.5 × 105 cells/well) and PDLCs (1.5 × 104 cells/well) were co-cultured for 7 days in the presence of M-CSF (30 ng/ml), RANKL (100 ng/mL), H2O2 (200 μM) or Tβ4 (0.5, 1 and 5 μg/mL) in α-MEM, supplemented with10% in 48-well plates under 5% CO2 atmosphere.
TB-500 is a synthetic fraction of the protein thymosin beta-4, which is present in virtually all human and animal cells. The main purpose of this peptide is to promote healing. It also promotes creation of new blood and muscle cells. The healing effects of TB-500 have been observed in tendons, ligaments, muscle, skin, heart, and the eyes. Thymosin beta-4 is naturally produced in higher concentration where tissue has been damaged. This peptide is also a very potent anti-inflamatory agent.
It was also shown recently that delivery of Fgfs by release from peptide nanofibers, a gradual local delivery system, can increase neovascularization and reduce in-farct size in the ischemic rodent heart (Engel et al., 2006). Related to this, zebrafish have a natural ability to synthesize Fgfs after myocardial injury, a signal that appears to recruit Fgf receptor-expressing epicardial-derived cells toward regenerating muscle (Lepilina et al., 2006). Thus, what has been and what will be discovered about zebrafish heart regeneration is quite likely to illuminate possible strategies for enhancing regeneration in the mammalian heart (see Chapter 14.4).
Half the group of burned volunteers got a whiff of Eau de Oxytocin, half got a sniff of Eau de Placebo. Those who sniffed the oxytocin were more trusting and ready to invest with an anonymous trustee a second time than were the placebo-exposed subjects. And when they were asked “Do you want to try this again?” the oxytocin-treated volunteers responded more quickly than the volunteers who hadn’t gotten the nose full of Trust Spray.6
These proteins, which typically contain 2-4 repeats of the β-thymosin sequence, are found in all phyla of the animal kingdom, with the probable exception of sponges The sole mammalian example, a dimer in mice, is synthesised by transcriptional read-through between two copies of the mouse β15 gene, each of which is also transcribed separately. A uniquely multiple example is the protein thypedin of Hydra which has 27 repeats of a β-thymosin sequence.
The short half-life (<2h) of 5-HTP may inherently limit the therapeutic potential of 5-HTP, as the systemic 5-HTP exposure levels will fluctuate substantially, even with relatively frequent dosing. Such exposure fluctuations are usually associated with increased adverse event burden, resulting from Cmax drug spikes, and decreased clinical efficacy resulting from sub-therapeutic exposure for large parts of the day. It has been proposed that 5-HTP dosage forms achieving prolonged delivery would be more effective, as is generally the situation with short-acting active pharmaceutical ingredients.