Tolerance enhancement of Dendrobium officinale by salicylic acid family-related metabolic pathways under unfavorable temperature.

BACKGROUND: Unfavorable temperatures significantly constrain the quality formation of Dendrobium officinale, severely limiting its food demand. Salicylic acid (SA) enhances the resistance of D. officinale to stress and possesses various analogs. The impact and mechanism of the SA family on improving the quality of D. officinale under adverse temperature conditions remains unclear. RESULTS: Combined with molecular docking analysis, chlorophyll fluorescence and metabolic analysis after treatments with SA analogues or extreme temperatures are performed in this study. The results demonstrate that both heat and cold treatments impede several main parameters of chlorophyll fluorescence of D. officinale, including the ΦPSII parameter, a sensitive growth indicator. However, this inhibition is mitigated by SA or its chemically similar compounds. Comprehensive branch imaging of ΦPSII values revealed position-dependent improvement of tolerance. Molecular docking analysis using a crystal structure model of NPR4 protein reveals that the therapeutic effects of SA analogs are determined by their binding energy and the contact of certain residues. Metabolome analysis identifies 17 compounds are considered participating in the temperature-related SA signaling pathway. Moreover, several natural SA analogs such as 2-hydroxycinnamic acid, benzamide, 2-(formylamino) benzoic acid and 3-o-methylgallic acid, are further found to have high binding ability to NPR4 protein and probably enhance the tolerance of D. officinale against unfavorable temperatures through flavone and guanosine monophosphate degradation pathways. CONCLUSIONS: These results reveal that the SA family with a high binding capability of NPR4 could improve the tolerance of D. officinale upon extreme temperature challenges. This study also highlights the collaborative role of SA-related natural compounds present in D. officinale in the mechanism of temperature resistance and offers a potential way to develop protective agents for the cultivation of D. officinale.

Cardio protective effect of nicorandil in reperfusion injury among patients undergoing primary percutaneous coronary intervention.

Objectives: To evaluate the effect of nicorandil in prevention of reperfusion injury during primary percutaneous coronary intervention by thrombolysis in myocardial infarction flow grade scoring. Methods: A total of 140 patients from Rawalpindi Institute of Cardiology were enrolled in this study conducted from 7th September to 10th of October 2021. These participants were allocated into two major groups. Control group received conventional acute coronary syndrome protocol regimen only whereas experimental group was given nicorandil along with conventional acute coronary syndrome protocol. During primary percutaneous coronary intervention, thrombolysis in myocardial infarction flow grade scoring was analyzed and compared. Results: Majority of participants in nicorandil group achieved thrombolysis in myocardial infarction Grade-3 scoring which indicated reduced rate of no reflow phenomenon as compared to control group. A statistically significant difference was noted in score of both groups (p value = 0.001) signifying prophylactic use of nicorandil before primary percutaneous coronary intervention along with conventional acute coronary syndrome protocol is superior to only conventional acute coronary syndrome protocol regimen to cases in the control group. Conclusion: Use of nicorandil in ST elevated myocardial infarction patients before primary percutaneous coronary intervention prevents reperfusion injury thus decreasing the risk of post percutaneous coronary intervention complications and reducing mortality rate in cardiac patients suggesting its significant cardio protective role.

[Research progress of irradiation injuries anti-agents].

Irradiation injuries anti-agents refer to drugs that can inhibit the initial stage of radiation injuries, or reduce the development of radiation injuries and promote the recovery of injuries when used early after irradiation exposure. According to the mechanism of action and the time of intervention, the irradiation injuries anti-agents are divided into four categories: radioprotectors, radiomitigators, radiation therapeutics for external radiation exposure, and anti-agents for internalized radionuclides. In this paper, the research progress of irradiation injuries anti-agents in recent years is reviewed.

New strategies to improve clinical outcomes for diabetic kidney disease.

BACKGROUND: Diabetic kidney disease (DKD), the most common cause of kidney failure and end-stage kidney disease worldwide, will develop in almost half of all people with type 2 diabetes. With the incidence of type 2 diabetes continuing to increase, early detection and management of DKD is of great clinical importance. MAIN BODY: This review provides a comprehensive clinical update for DKD in people with type 2 diabetes, with a special focus on new treatment modalities. The traditional strategies for prevention and treatment of DKD, i.e., glycemic control and blood pressure management, have only modest effects on minimizing glomerular filtration rate decline or progression to end-stage kidney disease. While cardiovascular outcome trials of SGLT-2i show a positive effect of SGLT-2i on several kidney disease-related endpoints, the effect of GLP-1 RA on kidney-disease endpoints other than reduced albuminuria remain to be established. Non-steroidal mineralocorticoid receptor antagonists also evoke cardiovascular and kidney protective effects. CONCLUSION: With these new agents and the promise of additional agents under clinical development, clinicians will be more able to personalize treatment of DKD in patients with type 2 diabetes.

Effects of freeze drying in complex lyoprotectants on the survival, and membrane fatty acid composition of Lactobacillus plantarum L1 and Lactobacillus fermentum L2.

The aim of this study was to investigate the effects of freeze-drying protective agents on the viability, survival and membrane fatty acid composition of Lactobacillus plantarum L1 and Lactobacillus fermentum L2. Cell survival rates of Lactobacillus plantarum L1 after freeze-drying without any additives was 6.57% (control group), 37.4% with a single protective agent, as compared to 97.4% when L.plantarum L1 was freeze-dried in a solution of four protectants (10% skim milk, 13% sucrose, 2% sorbitol, and 0.8% tyrosine (p < 0.05).) The L.fermentum L2 strain had the highest survival rate 92.3% when was freeze-dried in a solution containing 10% skim milk, 7% trehalose, 2% sorbitol and 0.6% tyrosine (p < 0.05). Freeze drying in the presence of all four protective agents maintained cell membrane integrity, as determined by reduced leakage of ß-galactosidase and LDH, and increased ATPase activity. LAB Incubation and freeze drying in the complex protective solution increased the content of unsaturated fatty acids in the cell membrane such as oleic acid (C18:1) and C19cyc11 and it is speculated that this may correlate with the improved outcomes.

Comparison of perianal skin barrier function with moisturizer application in Japanese full-term newborns.

BACKGROUND/OBJECTIVES: Some full-term newborns present with erythema and irritation of the buttocks and perianal area as early as the first 4 days of their lives. The effect of moisturizers in protecting this vulnerable skin has not been rigorously studied. This study aimed to clarify whether there is a difference in perianal skin barrier function with and without moisturizer application in the first month of life. METHODS: Comparative investigation of 118 full-term newborns was performed, and they were allocated to intervention (n = 63) and control groups (n = 55). The intervention group received moisturizer application to the perianal area, and the control group received care without application of moisturizer to the perianal area from the first day of life until the 1-month visit. Transepidermal water loss (TEWL), stratum corneum hydration (SCH), and skin surface pH in the perianal area were measured as the indicators of skin barrier function on days 1 and 5 after birth and at the 1-month visit. RESULTS: At the 1-month visit, TEWL was significantly decreased (intervention, 19.4 g/m2 /h; control, 25.8 g/m2 /h; p = .00) and SCH was significantly increased (intervention, 58.8 arbitrary units (a.u.); control, 46.5 a.u.; p = .00) in newborns using perianal moisturizer. The skin surface pH was not significantly different. CONCLUSIONS: The use of moisturizer was effective in protecting the skin barrier function of the perianal skin. Further investigations are needed to determine the effect on the frequency and extent of rashes in the perianal area.

A review on radiation induced nausea and vomiting: "Current management strategies and prominence of radio sensitizers".

Radiations dissipated are high energy waves used mostly as treatment intervention in controlling the unwanted multiplication of cell. About 60%-65% of cancer treatment requires radiation therapy and 40%-80% of radiation therapy causes RINV which are true troublemakers. Radiation therapy (RT) is targeted therapy mostly used to treat early stages of tumour and prevent their reoccurrence. They mainly destroy the genetic material (DNA) of cancerous cells to avoid their unwanted growth and division. The RINV affects the management and quality of life of patients which further reduces the patient outcome. RINV depends on RT related factors (dose, fractionation, irradiation volume, RT techniques) and patient related factors like (gender, health conditions, age, concurrent chemotherapy, psychological state, and tumour stage). RT is an active area of research and there is only limited progress in tackling the RINV crisis. Advanced technological methods are adopted that led to better understanding of total lethal doses. Radiation therapy also affects the immunity system that leads to radiation induced immune responses and inflammation. Radio sensitizers are used to sensitize the tumour cells to radiations that further prevent the normal cell damage from radiation exposure. There is a need for future studies and researches to re-evaluate the data available from previous trials in RINV to make better effective antiemetic regimen. The article focuses on radiation therapy induced nausea and vomiting along with their mechanism of action and treatment strategies in order to have a remarkable patient care.

Does the administration of meloxicam before head and neck radiotherapy reduce the risk of mandibular osteoradionecrosis? An animal model study.

OBJECTIVE: To assess whether the administration of meloxicam before head and neck radiotherapy reduces the risk of mandibular osteoradionecrosis in rats. MATERIAL AND METHODS: Sixty male Wistar rats were randomly divided into 6 groups (n = 10) according to the meloxicam administration and radiation therapy: control (C), irradiated (I), single dose of meloxicam (M1), single dose of meloxicam and irradiated (M1I), triple dose of meloxicam (M3), triple dose of meloxicam and irradiated (M3I). Meloxicam was administrated (20 mg/kg per dose) 1 h before the radiation therapy (single dose of 20 Gy) and 24 h and 48 h after the radiation therapy for groups with two additional doses. Ten days after the radiation therapy, the three right mandibular molars were extracted from all rats, who were euthanatized after 21 or 35 days (n = 5 per group). The mandibles were assessed by macroscopic evaluation and micro-CT analysis. RESULTS: The right hemimandibles of the irradiated groups revealed macroscopic signs of osteoradionecrosis, and those of the non-irradiated groups revealed complete gingival healing. A significant delay in alveolar socket healing in all irradiated groups was observed in the micro-CT assessment regardless meloxicam treatment. CONCLUSION: The administration of meloxicam before head and neck radiotherapy does not reduce the risk of mandibular osteoradionecrosis when associated to dental extractions. CLINICAL RELEVANCE: Since meloxicam has been shown to be a potential radiation-protective agent, and osteoradionecrosis physiopathology is believed to be related to an inflammatory process, possible interactions are relevant to be investigated.

Evaluation of Analytes Characterized with Potential Protective Action after Rat Exposure to Lead.

Lead (Pb) was revealed for its role as a neurodevelopmental toxin. The determination of neurotransmitters (NTs) in particular brain regions could ameliorate the precise description and optimization of therapeutic protocols able to restore the harmony of signaling pathways in nervous and immune systems. The determination of selected analytes from the group of NTs based on the liquid chromatography (LC)-based method was carried out to illustrate the changes of amino acid (AA) and biogenic amine (BA) profiles observed in chosen immune and nervous systems rat tissues after Pb intoxication. Also, a protective combination of AA was proposed to correct the changes caused by Pb intoxication. After the administration of Pb, changes were observed in all organs studied and were characterized by a fluctuation of NT concentrations in immune and nervous systems (hypothalamus samples). Using a protective mixture of bioactive compounds prevented numerous changes in the balance of NT. The combined analysis of the immune and nervous system while the normalizing effect of curative agents on the level of differentially secreted NTs and AA is studied could present a new approach to the harmonization of those two essential systems after Pb intoxication.

Bone Health Management After Hematopoietic Cell Transplantation: An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy.

Bone health disturbances commonly occur after hematopoietic cell transplantation (HCT) with loss of bone mineral density (BMD) and avascular necrosis (AVN) foremost among them. BMD loss is related to pretransplantation chemotherapy and radiation exposure and immunosuppressive therapy for graft-versus-host-disease (GVHD) and results from deficiencies in growth or gonadal hormones, disturbances in calcium and vitamin D homeostasis, as well as osteoblast and osteoclast dysfunction. Although the pathophysiology of AVN remains unclear, high-dose glucocorticoid exposure is the most frequent association. Various societal treatment guidelines for osteoporosis exist, but the focus is mainly on menopausal-associated osteoporosis. HCT survivors comprise a distinct population with unique comorbidities, making general approaches to bone health management inappropriate in some cases. To address a core set of 16 frequently asked questions (FAQs) relevant to bone health in HCT, the American Society of Transplant and Cellular Therapy Committee on Practice Guidelines convened a panel of experts in HCT, adult and pediatric endocrinology, orthopedics, and oral medicine. Owing to a lack of relevant prospective controlled clinical trials that specifically address bone health in HCT, the answers to the FAQs rely on evidence derived from retrospective HCT studies, results extrapolated from prospective studies in non-HCT settings, relevant societal guidelines, and expert panel opinion. Given the heterogenous comorbidities and needs of individual HCT recipients, answers to FAQs in this article should be considered general recommendations, with good medical practice and judgment ultimately dictating care of individual patients. Readers are referred to the Supplementary Material for answers to additional FAQs that did not make the core set.

Substituted Piperazines as Novel Potential Radioprotective Agents.

The increasing risk of radiation exposure underlines the need for novel radioprotective agents. Hence, a series of novel 1-(2-hydroxyethyl)piperazine derivatives were designed and synthesized. Some of the compounds protected human cells against radiation-induced apoptosis and exhibited low cytotoxicity. Compared to the previous series of piperazine derivatives, compound 8 exhibited a radioprotective effect on cell survival in vitro and low toxicity in vivo. It also enhanced the survival of mice 30 days after whole-body irradiation (although this increase was not statistically significant). Taken together, our in vitro and in vivo data indicate that some of our compounds are valuable for further research as potential radioprotectors.

[Radiation-protective agent and anti-aging agents: random and predictable matches.]

Radiation-protective and anti-aging properties are often combined. Combination of this properties is linked to the common mechanisms of action such as direct and indirect antioxidant activities, inhibition of free radicals formation, increase resistance to stress impacts at the cellular level, acceleration of DNA reparation, prevention of chronic diseases linked to abnormalities in regeneration processes, activation of immune inflammatory processes and carcinogenesis. Regulation of cell cycle and apoptosis can often be considered as an implementing driver of radiation-protective and anti-aging activities. On the one hand, against the background of stopping the cell cycle and blockade of apoptosis increases the time required to repair the defects of a DNA. Antiapoptotic effects enhances survival chances at the early stage after irradiation in a particular range of doses. On the other hand, activation of apoptosis of altered cells can be seen as one of the mechanisms to delay aging processes and prevention of isolated effects of exposure to ionizing radiation. Formation of radiation-induced and age-related alterations are characterized by multiple factors and a variety of manifestations. Nevertheless, similarity of individual links of the pathogenesis of disease related to radiation exposure and aging of the body is striking. It could be stated that radiation-protective property defines an increase in life expectancy by short-term exposure in sub-lethal and lethal doses. However anti-aging activities prevent the development of remote effects of ionizing radiation by prolonged low doses or fractionated exposure to radiation.

Thieno[2,3-d]pyrimidine as a promising scaffold in medicinal chemistry: Recent advances.

Thienopyrimidine scaffold is a fused heterocyclic ring system that structurally can be considered as adenine, the purine base that is found in both DNA and RNA-bioisosteres. Thienopyrimidines exist in three distinct isomeric forms. The current review discusses thieno[2,3-d]pyrimidine as a one of the opulent heterocycles in drug discovery. Its broad range of medical applications such as anticancer, anti-inflammatory, anti-microbial, and CNS protective agents has inspired us to study its structure-activity relationship (SAR), along with its relevant synthetic strategies. The present review briefly summarizes synthetic approaches for the preparation of thieno[2,3-d]pyrimidine derivatives. In addition, the promising biological activities of this scaffold are also illustrated with explanatory diagrams for their SAR studies.

The Effects of the CXCR4 Antagonist, AMD3465, on Human Retinal Vascular Endothelial Cells (hRVECs) in a High Glucose Model of Diabetic Retinopathy.

BACKGROUND High blood glucose levels in diabetes result in retinal angiogenesis, which is the key feature of diabetic retinopathy. This study aimed to investigate the effects of the CXCR4 antagonist, AMD3465, on human retinal vascular endothelial cells (hRVECs) [i]in vitro[/i]. MATERIAL AND METHODS Cell viability and the protein expression levels of CXCR4 and stromal cell-derived factor 1 (SDF-1) were evaluated in high glucose (HG)-treated human retinal vascular endothelial cells (hRVECs). The cell counting kit 8 (CCK-8) assay, the colony formation assay, immunofluorescence, and Western blot were used to investigate the effects of AMD3465 on hRVEC cell viability, colony formation, cell proliferation, and expression of CXCR4 and SDF-1. Cell apoptosis and angiogenesis were assessed by flow cytometry and Western blot. RESULTS Treatment with high glucose reduced the viability of hRVECs and increased the protein expression levels of CXCR4 and SDF-1. Following treatment with AMD3465, the colony formation capacity and cell proliferation in hRVECs increased, and there was a significant reduction in apoptosis rate compared with the untreated cells. AMD3465 significantly reduced the expression of angiogenesis-associated proteins, including ICAM1, VCAM1, VEGF, and AngII. AMD3465 significantly reduced the protein expression levels of TNF-α, IL-1ß, NF-κB, and p-p65. CONCLUSIONS The CXCR4 antagonist, AMD3465, reduced apoptosis of HG-treated hRVECs in an [i]in vitro[/i] model of diabetic retinopathy.

Using human iPS cell-derived enterocytes as novel in vitro model for the evaluation of human intestinal mucosal damage.

OBJECTIVE AND DESIGN: The primary component in gut mucus is mucin 2 (MUC2) secreted by goblet cells. Fluctuations in MUC2 expression are considered a useful indicator for evaluating mucosal damage and protective effect of various agents using animal studies. However, there are few in vitro studies evaluating mucosal damage using MUC2 as the indicator. Hence, we attempted to establish a novel in vitro model with MUC2 as the indicator for evaluating drug-induced mucosal damage and protective effect using enterocytes derived from human iPS cells. METHODS: Compounds were added into enterocytes derived from human iPS cells, and MUC2 mRNA and protein expression levels were evaluated. Further, the effect of compounds on membrane permeability was investigated. RESULTS: Nonsteroidal anti-inflammatory drugs were found to decrease MUC2 mRNA expression in enterocytes, whereas mucosal protective agents increased mRNA levels. Changes in MUC2 protein expression were consistent with those of mRNA. Additionally, our results indicated that indomethacin caused mucosal damage, affecting membrane permeability of the drug. Moreover, we observed protective effect of rebamipide against the indomethacin-induced permeability increase. CONCLUSIONS: The developed model could facilitate evaluating drug-induced mucosal damage and protective effects of various agents and could impact drug development studies regarding pharmacological efficacy and safety.

Improved stability of live attenuated vaccine gdhA derivative Pasteurella multocida B:2 by freeze drying method for use as animal vaccine.

The efficacy of attenuated strain of gdhA derivative Pasteurella multocida B:2 mutant as a live vaccine to control haemorrhagic septicaemia (HS) disease in cattle and buffaloes has been demonstrated. In order to use P. multocida B:2 mutant as a commercial product, it is essential to optimise its formulation for high viability and stability of the live cells. The effectiveness of freeze-drying process using different protective agent formulations for improving cells viability was explored. Sugar and nitrogen compounds were used as protective agents in freeze-drying and the capability of these compounds in maintaining the viability of mutant P. multocida B:2 during subsequent storage was investigated. A complete loss in viability of freeze-dried mutant P. multocida B:2 was monthly observed until 6-12 months of storage at -30 °C, 4 °C and 27 °C when nitrogen compound or no protective agent was added. Trehalose and sucrose showed significantly high survival rate of 93-95% immediately after freeze-drying and the viability was retained during the subsequent storage at -30 °C and 4 °C. A smooth cell surface without any cell-wall damage was observed for the cells formulated with trehalose under scanning electron micrograph. This study presented a freeze-drying process generating a dried live attenuated vaccine formulation with high stability for commercial applications.

Evaluation of rational nonsteroidal anti-inflammatory drugs and gastro-protective agents use; association rule data mining using outpatient prescription patterns.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) and gastro-protective agents should be co-prescribed following a standard clinical practice guideline; however, adherence to this guideline in routine practice is unknown. This study applied an association rule model (ARM) to estimate rational NSAIDs and gastro-protective agents use in an outpatient prescriptions dataset. METHODS: A database of hospital outpatients from October 1st, 2013 to September 30th, 2015 was searched for any of following drugs: oral antacids (A02A), peptic ulcer and gastro-oesophageal reflux disease drugs (GORD, A02B), and anti-inflammatory and anti-rheumatic products, non-steroids or NSAIDs (M01A). Data including patient demographics, diagnoses, and drug utilization were also retrieved. An association rule model was used to analyze co-prescription of the same drug class (i.e., prescriptions within A02A-A02B, M01A) and between drug classes (A02A-A02B & M01A) using the Apriori algorithm in R. The lift value, was calculated by a ratio of confidence to expected confidence, which gave information about the association between drugs in the prescription. RESULTS: We identified a total of 404,273 patients with 2,575,331 outpatient visits in 2 fiscal years. Mean age was 48 years and 34% were male. Among A02A, A02B and M01A drug classes, 12 rules of associations were discovered with support and confidence thresholds of 1% and 50%. The highest lift was between Omeprazole and Ranitidine (340 visits); about one-third of these visits (118) were prescriptions to non-GORD patients, contrary to guidelines. Another finding was the concomitant use of COX-2 inhibitors (Etoricoxib or Celecoxib) and PPIs. 35.6% of these were for patients aged less than 60 years with no GI complication and no Aspirin, inconsistent with guidelines. CONCLUSIONS: Around one-third of occasions where these medications were co-prescribed were inconsistent with guidelines. With the rapid growth of health datasets, data mining methods may help assess quality of care and concordance with guidelines and best evidence.

[Willingness and influencing factors of using pre-exposure prophylaxis among 301 men have sex with men in Wuhan city, 2015].

Objective: To understand willingness and influencing factors of using pre-exposure prophylaxis (Pr-EP) among men who have sex with men (MSM). Methods: Snow ball sampling was employed to recruit MSM in the social spaces (like bars and bathrooms) with focused activities by MSM and internet (QQ and Wechat) in Wuhan between August and November, 2015. 304 MSM were considered eligible when they were self-identified MSM and has had sex with men in the previous 12 months, over the age of 18 and have full civil liability. On-site and online questionnaire surveys were conducted by self-designed questionnaires to collect information including demographic characteristics, sexual risks and practices, awareness of PrEP, and willingness to use PrEP. A total of 301 qualified questionnaires were obtained. Multivariate logistic regression models were constructed to identify factors associated with willingness to use Pr-EP. Results: The mean age of surveyed MSM were (27.51±8.31) years, between18-61. 149 on-site survey, online were152; 131 MSM have regular homosexual partners, 170 MSM have not regular homosexual partners. Only 17.28% (52/301) had heard of Pr-EP before this survey, 18.32% (24/130) had heard of Pr-EP among those who had regular homosexual partners and those who had not accounted for 16.47% (28/170). 74.42% (224/301) had willingness to use Pr-EP after they knew Pr-EP was safe and effective through the survey. The proportion among those who had regular homosexual partners was 74.05%(74), and the proportion among those who had not was 74.71% (127); Among those who had regular homosexual partners, results suggested that those who were married/cohabiting were more likely to report a willingness to use PrEP compared to unmarried/divorced or widowed (OR=5.60), compared with homosexual, heterosexuality was associated with decreased odds of willingness to use Pr-EP (OR= 0.22), compared with HIV status of sexual partner was negative or uncertain, positive infection status was associated with increased odds of willingness to use (OR=7.52). Compared with MSM who have not regular homosexual partners, those who were married/cohabiting were more likely to report a willingness to use PrEP compared to unmarried/divorced or widowed (OR=9.09), compared with those who think they have risk of infection, those who do not think they have risk of infection was associated with decreased odds of willingness to use Pr-EP (OR= 0.30), compared with those with a high frequency to seek sexual partners, those not often to seek was associated with decreased odds of willingness to use Pr-EP (OR= 0.27). All above P values were<0.05. Conclusion: The awareness rate of Pr-EP among MSM in Wuhan is low in 2015, but the willingness to use Pr-EP could get a considerable increase after introduction. It is considered that promotion of Pr-EP is feasible in China, and there are different influencing factors for the willingness between two MSM subgroups (having regular homosexual partners and having no regular homosexual partners).

Vascular surgery-related organ injury and protective strategies: update and future prospects.

Whilst there has been a reduction in the prevalence of peripheral vascular disease worldwide, a significant proportion of the world's growing population is still affected by disease of the aorta, carotid, iliac and lower limb arteries. These if left untreated can result in severe morbidity and mortality. However vascular surgery, the main definitive treatment for such conditions, is associated with subsequent injury to vital organs including the kidneys, heart, brain, intestines and lungs, with a consequent increase in both morbidity and mortality. The current thinking is that the underlying mechanism of injury is direct organ ischaemia and ischaemia induced formation of free radicals, cytokine release and mitochondrial failure. Various methods to alleviate such injuries have been investigated including pre- and postconditioning strategies, pharmacological therapies including volatile anaesthetic and alpha2 adrenoceptor agonist drugs and more recently remote conditioning strategies. Although these interventions have demonstrated some reduction in the biomarkers for organ injury, attempts to translate these benefits into clinical practice have not been successful in terms of morbidity, mortality or length of hospital stay. For this reason, further research is needed in this area to facilitate the translation of the potential interventional benefits from bench to bedside.

Effects of Arbutin on Radiation-Induced Micronuclei in Mice Bone Marrow Cells and Its Definite Dose Reduction Factor.

BACKGROUND: Interactions of free radicals from ionizing radiation with DNA can induce DNA damage and lead to mutagenesis and carsinogenesis. With respect to radiation damage to human, it is important to protect humans from side effects induced by ionizing radiation. In the present study, the effects of arbutin were investigated by using the micronucleus test for anti-clastogenic activity, to calculate the ratio of polychromatic erythrocyte to polychromatic erythrocyte plus normochromatic erythrocyte (PCE/PCE+NCE) in order to show cell proliferation activity. METHODS: Arbutin (50, 100, and 200 mg/kg) was intraperitoneally (ip)administered to NMRI mice two hours before gamma radiation at 2 and 4 gray (Gy). The frequency of micronuclei in 1000 PCEs (MnPCEs) and the ratio of PCE/PCE+NCE were calculated for each sample. Data were statistically evaluated using one-way ANOVA, Tukey HSD test, and t-test. RESULTS: The findings indicated that gamma radiation at 2 and 4 Gy extremely increased the frequencies of MnPCE (P<0.001) while reducing PCE/PCE+NCE (P<0.001) compared to the control group. All three doses of arbutin before irradiation significantly reduced the frequencies of MnPCEs and increased the ratio of PCE/PCE+NCE in mice bone marrow compared to the non-drug-treated irradiated control (P<0.001). All three doses of arbutin had no toxicity effect on bone marrow cells. The calculated dose reduction factor (DRF) showed DRF=1.93 for 2Gy and DRF=2.22 for 4 Gy. CONCLUSION: Our results demonstrated that arbutin gives significant protection to rat bone against the clastogenic and cytotoxic effects of gamma irradiation.