The Effect of Polydeoxyribonucleotide on Chronic Non-healing Wound of an Amputee: A Case Report

Polydeoxyribonucleotide (PDRN) is safe and effective in wound healing, cellular growth, synthesis of extracellular matrix protein, and inflammation reduction via activation of adenosine A2 receptors. We report a 28-year-old male patient treated with PDRN injections for chronic non-healing wound refractory to negative pressure wound therapy, skin graft, or growth factors. Three injections of PDRN were administered at the wound site into the anterior and medial sides of the left stump on the 1st, 4th, and 9th days of hospitalization. The PDRN ameliorated wound healing by enhancing cell growth, tissue repair, and angiogenesis. PDRN application represents a potential treatment for non-healing wounds obviating the need for additional therapies, and hospitalization, as well as improve patient’s activities of daily living.

role of the A2A receptor in cell apoptosis caused by MDMA

Ecstasy, also known as 3, 4-methylenedioxymethamphetamine [MDMA], is a psychoactive recreational hallucinogenic substance and a major worldwide recreational drug. There are neurotoxic effects observed in laboratory animals and humans following MDMA use. MDMA causes apoptosis in neurons of the central nervous system [CNS]. Withdrawal signs are attenuated by treatment with the adenosine receptor [A2A receptor]. This study reports the effects of glutamyl cysteine synthetase [GCS], as an A2A receptor agonist, and succinylcholine [SCH], as an A2A receptor antagonist, on Sprague Dawley rats, both in the presence and absence of MDMA. In this experimental study, we used seven groups of Sprague Dawley rats [200-250 g each]. Each group was treated with daily intraperitoneal [IP] injections for a period of one week, as follows: i. MDMA [10 mg/kg]; ii. GCS [0.3 mg/kg]; iii. SCH [0.3 mg/kg]; iv. GCS + SCH [0.3 mg/kg each]; v. MDMA [10 mg/kg] + GCS [0.3 mg/kg]; vi. MDMA [10 mg/kg] + SCH [0.3 mg/kg]; and vi. normal saline [1 cc/kg] as the sham group. Bax [apoptotic protein] and Bcl-2 [anti-apoptotic protein] expressions were evaluated by striatum using RT-PCR and Western blot analysis. There was a significant increase in Bax protein expression in the MDMA+SCH group and a significant decrease in Bcl-2 protein expression in the MDMA+SCH group [p<0.05]. A2A receptors have a role in the apoptotic effects of MDMA via the Bax and Bcl-2 pathways. An agonist of this receptor [GCS] decreases the cytotoxcity of MDMA, while the antagonist of this receptor [SCH] increases its cytotoxcity

Establishment and evaluation of brain adenosine A2A receptors inactivation model of mice / 生物工程学报

To establish a model of inactivation adenosine A2A receptors in brain tissues of mice, we transplanted bone marrow cells (BMCs) from wild type (WT) C57BL/6 mice into A2A receptor knockout (A2A KO) C57BL/6 mice which were previously fractionated total body irradiation of 6.2 Gyx2. Six weeks later, we identified and evaluated the model. The results showed that the sexual chromagene pattern on white blood cells of recipient mice changed from female pattern to male pattern and there were 95.9% of A2AR+ cells in peripheral white blood cells of recipient mice, whereas there was no significant difference of A2AR mRNA level in brains between these recipient mice and A2AR KO mice. Furthermore, there was no significant difference of breathing frequency, brain water content and level of glutamate between the model mice and WT mice. These results indicated that we established successfully a mouse model of inactivation adenosine A2A receptors in brain tissues. This may provide a new and efficient strategy to study the effect of adenosine A2A receptors in disease and injuries of central nervous system.

The Effects of Adenosine on Enhanced ICAM-1 Expression by IFN-gamma in Cultured Human Keratinocyte Cell Line HaCaT Cells / 대한피부과학회지

BACKGROUND: Intercellular adhesion molecule(ICAM)-1 mediates cell to cell adhesion by acting as a receptor for leukocyte surface antigen. Increased ICAM-1 expression was observed in chronic inflammatory skin diseases, such as psoriasis, atopic dermatitis and allergic contact dermatitis. Adenosine is an endogenous antiinflammatory agent released by cells under metabolically unfavorable conditions, recently the studies about antiinflammatory effects of adenosine in various tissues were increased, but there are few studies about the effect of adenosine on epidermal keratinocytes. OBJECTIVE: We investigated the effects of adenosine on ICAM-1 expression in cultured human keratinocyte cell line HaCaT cells. METHODS: Our study analyses the ICAM-1 expression in HaCaT cells by various stimulants and the effects of adenosine, adenosine receptor agonist&antagonist and an inhibitor of cellular adenosine uptake on ICAM-1 expression of cells stimulated by IFN-gamma through the cell-ELISA (enzyme-linked immunosorbent assay)&FACS (fluorescence-activated cell sorter) analysis. RESULTS: The results are summerized as follows: 1. ICAM-1 expression was significantly increased by IFN-gamma(500U/ml), IFN-gamma&TNF-alpha(10-8M) and IFN-gamma&LPS(10-8M)(p<0.05), but not by TNF-alpha, LPS and TNF-alpha & LPS. 2. Incubation of HaCaT cells with IFN-gamma(1-2000U/ml) for 48 hours induced dose-dependent expression of ICAM-1 at above 500U/ml of IFN-gamma. 3. Adenosine had no effect on ICAM-1 expression of unstimulated cells. 4. Adenosine(esp. 10-4M) significantly inhibited ICAM-1 expression of cells stimulated by IFN-gamma(p<0.01). 5. Adenosine(10-4M) significantly inhibited ICAM-1 expression of cells stimulated by IFN-gamma(p<0.01), IFN-gamma & TNF-alpha(p<0.05) and IFN-gamma&LPS. 6. The inhibition of ICAM-1 expression was not observed when cells were preincubated with an adenosine A1 receptor agonist(R-PIA) or an adenosine A2 receptor agonist (NECA). 7. The inhibition of ICAM-1 expression of adenosine was not affected by pretreatment state with an adenosine A1 & A2 receptor antagonist(theophylline)(p<0.01). 8. The inhibition of ICAM-1 expression of adenosine was not observed by pretreatment state with an inhibitor of adenosine cellular uptake (dipyridamole). CONCLUSION: High concentration of adenosine inhibits enhanced ICAM-1 expression on HaCaT cells by stimulated with IFN-gamma and these inhibitory effects of adenosine are mediated through other adenosine receptors excect adenosine A1 and A2 receptors. And we suggest that there may be an unknown intracellular mechanism about inhibition of ICAM-1 expression via intracellular-uptaken adenosine.

Renin Release by Adenosine Agosists and Antagonists in Two-Kidney One Clip Goldblatt Hypertensive Rats / 대한내분비학회지

BACKGROUND: In two-kidney one clip Goldbaltt hypertensive rats(2K1C GHR), clipped kidney may be exposed to low pressure and unclipped kidney to high pressure. In addition, both kidneys may have a different amount of adenosine which is increased by ischemia and plays an important role for renin release. The aim of this study was to invstigate the responsmiveness for renin release to adenosine agonists and antagonist in clipped and unclipped kidney of 2K1C GHR. METHODS: Emplying kidney slices from both unclipped and unclipped kidney of 2K1C GHR, the alteration by adenosine agonists and antagonist of renin release was studied. RESULTS: The renal renin content and basal renin release from unclipped kidney slices were suppressed, whereas those from clipped kidney were augmented Adenosine Al receptor agonist, cyclohexyladenosne(CHA), phenylisopropyl adenosine(PIA) and adenosine caused a decrease in renin release from clipped kidney slices. Adenosine A2 receptor agonist, NECA, and nonspecific adenosine receptor aganist, 2-chloroadenosine(CA) caused an increase in renin release from clipped kidney slices. Adenosine receptor antagonist, 8-phenyltheophylline(8-PT) caused an increase in renin release from clipped kidney slices. In unclipped kidney, however, the renin release in response to NECA, CA or 8-PT was reversed and the decreasing effect of renin release to CHA and adenosine was slightly inereased. CONCLUSION: These results suggest that the responsiveness of adenosine receptors, which may participate in renin release is modified in clipped and unclipped kidney of 2K1C GHR.