The Involvement of Macrophage Colony Stimulating Factor on Protein Hydrolysate Injection Mediated Hematopoietic Function Improvement.

Protein hydrolysate injection (PH) is a sterile solution of hydrolyzed protein and sorbitol that contains 17 amino acids and has a molecular mass of 185.0-622.0 g/mol. This study investigated the effect of PH on hematopoietic function in K562 cells and mice with cyclophosphamide (CTX)-induced hematopoietic dysfunction. In these myelosuppressed mice, PH increased the number of hematopoietic cells in the bone marrow (BM) and regulated the concentration of several factors related to hematopoietic function. PH restored peripheral blood cell concentrations and increased the numbers of hematopoietic stem cells and progenitor cells (HSPCs), B lymphocytes, macrophages, and granulocytes in the BM of CTX-treated mice. Moreover, PH regulated the concentrations of macrophage colony stimulating factor (M-CSF), interleukin (IL)-2, and other hematopoiesis-related cytokines in the serum, spleen, femoral condyle, and sternum. In K562 cells, the PH-induced upregulation of hematopoiesis-related proteins was inhibited by transfection with M-CSF siRNA. Therefore, PH might benefit the BM hematopoietic system via the regulation of M-CSF expression, suggesting a potential role for PH in the treatment of hematopoietic dysfunction caused by cancer therapy.

Does routine topical antimicrobial administration prevent sternal wound infection after cardiac surgery?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'Does routine topical antimicrobial administration prevent sternal wound infection (SWI) after cardiac surgery? Altogether >238 papers were found using the reported search, of which 11 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Several different antimicrobial agents, dosages and application protocols were found in the literature. Regarding topical vancomycin use, a meta-analysis by Kowalewski et al. demonstrated a 76% risk reduction in any SWI. Collagen-gentamicin sponge application was associated with a 38% risk reduction in SWI in another meta-analysis by Kowalewski et al., which included 4 randomized control trials and >23 000 patients. Lower evidence observational studies found benefit in the use of different regimes, including: combination of vancomycin paste and subcutaneous gentamycin; combined cefazoline and gentamicin spray; isolated cefazolin; bacitracin ointment; and rifampicin irrigation. We conclude that, in light of the body of evidence available, topical antibiotic application prevents SWI, including both superficial and deep SWI. The strongest evidence, derived from 2 meta-analyses, is related to the use of gentamicin-collagen sponges and topical vancomycin. Heterogeneity throughout studies regarding antibiotic agents, dosages, application protocols and SWI definition makes providing general recommendations challenging.

Comparison of bone wax and chitosan usage on post-sternotomy bone healing.

BACKGROUND: Sternotomy is a standard approach performed in almost every surgical procedure on the heart and mediastinum. Effective hemostasis of the sternum is required to keep the operative field dry, avoid excessive blood transfusions during surgery, and prevent reoperation due to massive postoperative bleeding, which can further increase morbidity and mortality in patients. Bone wax is a mechanical hemostat commonly used after sternotomy and has been known to affect bone healing, trigger chronic inflammatory reactions, and increase the rate of infection. The application of chitosan, which has intrinsic hemostat ability, as hemostatic material is believed to improve bone healing following sternotomy. This study aimed to compare the effectiveness of bone wax and chitosan on bone healing after sternotomy. METHODS: Median sternotomies were performed on 2 groups of New Zealand White rabbits. Each group of 16 animals received either bone wax or chitosan powder as hemostatic material. The degree of bone healing, the number of foreign-body giant cells, and the number of osteoblasts were evaluated after 6 weeks. RESULTS: Radiographs showed that significantly more animals in the chitosan group had total sternal healing (p = 0.033). Histopathology revealed that the number of foreign-body giant cells was significantly less (p = 0.036) and the number of osteoblasts was significantly greater (p < 0.0001) in the group of animals that received chitosan. CONCLUSION: The use of chitosan as hemostatic material can promote better bone healing compared to bone wax.

The evaluation of embryotoxicity of Ligusticum chuanxiong on mice and embryonic stem cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Chuanxiong (Chuanxiong Rhizoma, CR), the dried rhizome of Ligusticum chuanxiong Hort, has been used during pregnancy for more than 2000 years. However, the embryotoxicity of CR was not evaluated so far. The purpose of this study was to examine the safety and rational use of CR during pregnancy on mice and mouse embryonic stem cell (ES), and to explore the mechanism of embryotoxicity. AIM OF THE STUDY: This study was carried out to evaluate embryotoxicity of CR decoction in vivo and in vitro, and to explore the mechanism of embryotoxicity from the perspective of bone metabolism. MATERIALS AND METHODS: In animal experiments, pregnant mice were randomly assigned into 5 groups, i.e. mice were orally treated with CR decoction at dosages of 0 (distilled water, as negative controls), 2, 8, 32 g/kg/d (low, medium and high-dose group), and vitamin A (as positive controls), respectively. Maternal and embryo-fetal parameters were registered after cesarean section. The fetal skeletal development was further assessed with the alizarin red S and Hematoxylin-Eosin staining (H&E staining) and fluorescent imaging. Meanwhile, the mouse embryonic stem cell test model (EST model) was established to objectively evaluate the toxicity of CR on the embryo development. The median inhibitory proliferation values (IC50) for both the mouse embryonic stem cell D3 (ES) and mouse embryonic fibroblast 3T3 (3T3) were detected with MTT assays. After removal of inhibiting factor (LIF), mouse embryonic stem cells spontaneously differentiated into cardiomyocytes, the expression of specific myosin heavy chain gene (ß-MHC) contained in cardiomyocytes were detected by q-PCR quantitative analysis, and median inhibitory differentiation concentration (ID50) of ES was obtained. The development toxicity calculation formula was used to determine the embryotoxicity grade of CR decoction. finally, based on the successful induction of osteoblasts, the molecular mechanism of CR embryotoxicity was preliminarily studied based on BMP-Smads signal pathway. RESULTS: Compared with the negative control group, high, medium, and low doses of CR decoction had no significant effect on the maternal body weight and uterine weight (P > 0.05), as well as on the maternal liver, heart, and kidneys. The observation results showed that high dose of CR decoction significantly increase the number of absorbed fetuses (P < 0.05). The EST model was successfully established, the IC50 3T3, IC50 ES and ID50 ES of CR were 9.39 mg/mL, 18.78 mg/mL, and 10.20 mg/mL, respectively. CR was classified as weak embryonic development toxicity by the EST linear discriminant formula. Meanwhile, osteoblasts were successfully induced in vitro, the relative expression levels of BMP2, BMPR2, Smad1, and Smad5 were down-regulated in varying degrees after 3, 6, and 9 days of treatment with different concentration gradients of CR decoction. CONCLUSIONS: Combining in vivo and in vitro experiments, CR showed a potential embryotoxicity. The mechanism of embryotoxicity may be related to inhibiting the expression of key genes in the BMP-SMADs signaling pathway. In the clinical application, the normal dosage of CR is safe to a certain extent. However, when the dosage is too high (160 g/60 kg/d), there may be a risk of embryotoxicity.

Effects of enhancing vitamin D status by 25-hydroxycholecalciferol supplementation, alone or in combination with calcium and phosphorus, on sternum mineralisation and breast meat quality in broilers.

1. The aim of the present study was to examine the effects of improving vitamin D status in broiler diets by supplementary 25-hydroxycholecalciferol (25OHD3), alone or in combination with calcium (Ca) and available phosphorus (aP), on live performance, sternum mineralisation and breast meat quality in broilers. 2. A total of 936 1-d-old Ross 308 broilers were used in the study. After gender determination at the hatchery, chicks from each sex were randomly distributed into three dietary treatments. The following dietary treatments were used in the experiment from hatch to 38 d: (1) A control diet formulated to meet all of the nutrient requirements of broiler chicks according to the management guide; (2) The control diet supplemented with 18.7-15.0 µg/kg of 25OHD3; and (3) The control diet supplemented with 18.7-15.0 µg/kg of 25OHD3 plus Ca + aP. 3. Improvement in vitamin D status by 25OHD3 supplementation, alone or in combination with Ca and aP, had no effect on body weight and feed conversion ratio of broilers. 4. The serum 25OHD3 concentration significantly increased with 25OHD3 and 25OHD3 plus Ca + aP supplementation (P < 0.05), whereas the ionised Ca and Mg concentrations remained unchanged. 5. Sternum absolute weight, ash content and the concentrations of Ca and P significantly increased (P < 0.01) with supplementation of 25OHD3, alone or in combination with Ca + aP. 6. Supplemental 25OHD3, alone or in combination with Ca + aP, slightly increased pH24 (P = 0.05) and decreased (P < 0.01) squeezable water loss in breast meat, whereas it had no significant effect on lightness, yellowness and sarcoplasmic protein solubility. 7. In conclusion, the results suggested that enhancing vitamin D status by 25OHD3 supplementation alone or in combination with Ca + aP may improve sternum structure and mineral accretion. Furthermore, supplemental 25OHD3, even in a nutritionally complete diet, may offer an effective way to improve protein solubility in female broilers.

Phenamil, an amiloride derivative, restricts long bone growth and alters keeled-sternum bone architecture in growing chickens.

"Broiler-type" chickens are fast-grow-ing, heavy-bodied birds with high demands on bone quality. Phenamil increased mineralization in cultured murine mesenchymal stem cells. Phenamil effects were tested in 2 groups of weight and gender matched day-old broiler chickens (n = 13). Oral administration of 30 mg phenamil/kg body weight d 1 to 13 reduced growth of chicks d 5 to 14 (P = 0.002); with phenamil-treated (PT) chick body weight being 84% of vehicle-treated (VT) chicks' body weight on d 14. Tissues collected on d 15 showed that femur lengths and widths did not differ, but tibias from PT chicks were 6% shorter (P = 0.002) and 13% narrower (P = 0.012) with 18% thinner tibial cross-sections (P < 0.008) than in VT chicks. Angles of the caudal aspect of the anterior surface of keeled-sternums were 166° in PT chicks, flatter than the 148° found in VT chicks (P = 0.000). Total mineral content of both tibia and femur were lower in PT chicks (P = 0.005 for both). Bone Ca, P, and Mg (ppm) in ash were similar, but Ca:P was lower (1.70 vs 1.75) in PT versus VT chicks (P < 0.05). Osteocalcin was ∼20% lower (P = 0.020), PINP was ∼45% higher (P = 0.000) in PT chicks. Carboxy-terminal telopeptide type I collagen (ICTP) and cross-linked N-telopeptide of type I collagen (NTX1) were similar in the 2 groups. Phenamil had unexpected and detrimental effects on bone formation in growing broiler chicks, reducing linear skeletal growth and markedly changing bone architecture.

Bilateral sternal infusion of ropivacaine and length of stay in ICU after cardiac surgery with increased respiratory risk: A randomised controlled trial.

BACKGROUND: The continuous bilateral infusion of a local anaesthetic solution around the sternotomy wound (bilateral sternal) is an innovative technique for reducing pain after sternotomy. OBJECTIVE: To assess the effects of the technique on the need for intensive care in cardiac patients at increased risk of respiratory complications. DESIGN: Randomised, observer-blind controlled trial. SETTING: Single centre, French University Hospital. PATIENTS: In total, 120 adults scheduled for open-heart surgery, with one of the following conditions: age more than 75 years, BMI >30 kg m, chronic obstructive pulmonary disease, active smoking habit. INTERVENTION: Either a bilateral sternal infusion of 0.2% ropivacaine (3 ml h through each catheter; 'intervention' group), or standardised care only ('control' group). Analgesia was provided with paracetamol and self-administered intravenous morphine. MAIN OUTCOME MEASURES: The length of time to readiness for discharge from ICU, blindly assessed by a committee of experts. RESULTS: No effect was found between groups for the primary outcome (P = 0.680, intention to treat); the median values were 42.4 and 37.7 h, respectively for the control and intervention groups (P = 0.873). Similar nonsignificant trends were noted for other postoperative delays. Significant effects favouring the intervention were noted for dynamic pain, patient satisfaction, occurrence of nausea and vomiting, occurrence of delirium or mental confusion and occurrence of pulmonary complications. In 12 patients, although no symptoms actually occurred, the total ropivacaine plasma level exceeded the lowest value for which neurological symptoms have been observed in healthy volunteers. CONCLUSION: Because of a small size effect, and despite significant analgesic effects, this strategy failed to reduce the time spent in ICU. TRIAL REGISTRATION: EudraCT (N°: 2012-005225-69); ClinicalTrials.gov (NCT01828788).

In vivo assessment of bone marrow toxicity by gold nanoparticle-based bioconjugates in Crl:CD1(ICR) mice.

INTRODUCTION: The present study aimed at evaluating the biodistribution of Tween(®) 20-gold nanoparticle (GNP) conjugates and their potential toxicity on the bone marrow before moving on to Phase I clinical trials. MATERIALS AND METHODS: Tween(®) 20-conjugated GNPs were injected intravenously for 21 days in male Crl:CD1(ICR) mice. Body weight of the mice was evaluated each day. After the sub-chronic Tween(®) 20-GNPs administration, blood samples were harvested, and a full blood count was done individually. Total Au quantity from all major organs was assessed using inductively coupled plasma mass spectrometry. One femur and the sternum obtained from each animal were used for histological assessment. RESULTS: Our data showed that the Tween(®) 20-GNP conjugates were found in large quantities in the bladder. Au was shown to accumulate in the hematopoietic bone tissue, with significant side effects such as leucopoiesis and megakaryopoiesis. The mice had a higher white blood cell and platelet count as opposed to the control group. This suggested that the previously described leukopenic effects of isoflurane were overridden by the leucopoietic effects of Tween(®) 20-GNPs. CONCLUSION: It was uncertain whether the mice were reactive to Au as it is a foreign substance to the tissues or whether the side effects observed were a precursor condition of a more severe hematological condition. Au was found to be hepatotoxic, urging the need for further studies in order to achieve better in vivo compliance and exploit the immense potential of GNPs in cancer pharmacology.

Combined exposure to big endothelin-1 and mechanical loading in bovine sternal cores promotes osteogenesis.

Increased bone formation resulting from mechanical loading is well documented; however, the interactions of the mechanotransduction pathways are less well understood. Endothelin-1, a ubiquitous autocrine/paracrine signaling molecule promotes osteogenesis in metastatic disease. In the present study, it was hypothesized that exposure to big endothelin-1 (big ET1) and/or mechanical loading would promote osteogenesis in ex vivo trabecular bone cores. In a 2×2 factorial trial of daily mechanical loading (-2000µÎµ, 120cycles daily, "jump" waveform) and big ET1 (25ng/mL), 48 bovine sternal trabecular bone cores were maintained in bioreactor chambers for 23days. The bone cores' response to the treatment stimuli was assessed with percent change in core apparent elastic modulus (ΔEapp), static and dynamic histomorphometry, and prostaglandin E2 (PGE2) secretion. Two-way ANOVA with a post hoc Fisher's LSD test found no significant treatment effects on ΔEapp (p=0.25 and 0.51 for load and big ET1, respectively). The ΔEapp in the "no load + big ET1" (CE, 13±12.2%, p=0.56), "load + no big ET1" (LC, 17±3.9%, p=0.14) and "load + big ET1" (LE, 19±4.2%, p=0.13) treatment groups were not statistically different than the control group (CC, 3.3%±8.6%). Mineralizing surface (MS/BS), mineral apposition (MAR) and bone formation rates (BFR/BS) were significantly greater in LE than CC (p=0.037, 0.0040 and 0.019, respectively). While the histological bone formation markers in LC trended to be greater than CC (p=0.055, 0.11 and 0.074, respectively) there was no difference between CE and CC (p=0.61, 0.50 and 0.72, respectively). Cores in LE and LC had more than 50% greater MS/BS (p=0.037, p=0.055 respectively) and MAR (p=0.0040, p=0.11 respectively) than CC. The BFR/BS was more than two times greater in LE (p=0.019) and LC (p=0.074) than CC. The PGE2 levels were elevated at 8days post-osteotomy in all groups and the treatment groups remained elevated compared to the CC group on days 15, 19 and 23. The data suggest that combined exposure to big ET1 and mechanical loading results in increased osteogenesis as measured in biomechanical, histomorphometric and biochemical responses.

[[Treatment and prophylaxis of complications of the sternotomy access in thoracic operations].]

Literature data and own experience of the treatment complications, occurring after tho- racic operations, using sternotomy access, were presented. Special attention was drawn to postoperative sternomediastinitis - most frequent infectious complication. Measures for the sternomediastinitis prophylaxis, methods of its diagnosis and treat- ment were presented.

T-2 Toxin Alters the Levels of Collagen II and Its Regulatory Enzymes MMPs/TIMP-1 in a Low-Selenium Rat Model of Kashin-Beck Disease.

The objectives of this study are to assess T-2 toxin's involvement in low selenium (Se)-induced Kashin-Beck disease (KBD) in rats and unveil the mechanisms underlying this disease. Two hundred thirty rats were randomly divided into two groups after weaning and fed normal or low-Se diets (n = 115), respectively, for a month. After low-Se model confirmation, rats in each group were subdivided into five: two subgroups (n = 20) were fed their current diets (normal or low-Se diets, respectively) for 30 and 90 days, respectively; two other subgroups (n = 25) received their current diets + low T-2 toxin (100 ng/g BW/day) for 30 and 90 days, respectively; and 25 rats were fed their current diets + high T-2 toxin (200 ng/g BW/day) for 30 days. Articular cartilage samples were extracted for hematoxylin and eosin (H&E) staining and immunohistochemistry. Western blot and reverse transcription-polymerase chain reaction (RT-PCR) were used to assess protein and mRNA levels, respectively, of collagen II, matrix metalloproteinase (MMP-1), MMP -3, MMP-13, and tissue inhibitor of metalloproteinase-1 (TIMP-1). Low Se and T-2 toxin synergistically affected animal fitness. Interestingly, low Se + T-2 toxin groups showed KBD characteristics. MMP-1, -3, and -13 mRNA and protein levels generally increased in low-Se groups, while collagen II and TIMP-1 levels showed a downward trend, compared with normal diet fed animals for the same treatment (P < 0.05). T-2 toxin's effect was dose but not time dependent. Low Se and T-2 toxin synergistically alter the expression levels of collagen II as well as its regulatory enzymes MMP-1, MMP-3, MMP-13, and TIMP-1, inducing cartilage damage. Therefore, T-2 toxin may cause KBD in low-Se conditions.

Maternal rat serum concentrations of dimethadione do not explain intra-litter differences in the incidence of dimethadione-induced birth defects, including novel findings in foetal lung.

To investigate mechanisms of chemical-induced congenital heart defects (CHD) we have developed a rat model using dimethadione (DMO), the N-demethylated metabolite of the anticonvulsant, trimethadione (TMD). Dosing pregnant rats with 300mg/kg DMO every 12h from the evening of gestational day (GD) 8 until the morning of GD 11 (six total doses) produces a mean 74% incidence of CHD with inter litter variability ranging from 40 to 100%. The goal of this study was to determine if the variability in maternal serum concentrations of DMO on GD 14, a surrogate marker for total exposure, was related to the inter-litter differences in teratogenic outcomes. To test this hypothesis, pregnant rats were dosed as described above and serum levels of DMO assessed on GD 14. On GD 21, foetuses were collected by caesarean section, assessed for a number endpoints and the outcomes were correlated with the GD 14 serum concentrations of DMO. DMO exposure was associated with decreased foetal body weight, increased incidence of sternal defects and CHD, but these endpoints were not meaningfully correlated with maternal concentrations of DMO. Novel findings were decreased viability as measured one-hour following caesarean section, and delayed alveolar maturation. The major conclusions from these studies were first, that serum DMO concentrations on GD 14 did not predict teratogenicity, and second, delayed lung development may contribute to the decreased survival of foetuses at the time of caesarean section.

A specific groove design for individualized healing in a canine partial sternal defect model by a polycaprolactone/hydroxyapatite scaffold coated with bone marrow stromal cells.

The reconstruction of sternal defects remains clinically challenging for thoracic surgeons. Here we aimed to explore the individualized reconstruction of partial sternal defects with new biodegradable material in a large animal model. We used the fused deposition modeling (FDM) technique to manufacture polycaprolactone/hydroxyapatite (PCL/HA) tissue scaffolds with individualized grooves to repair the sternal defect. The defects were surgically created in a sternocostal joint of eighteen Beagle dogs. The animals were separated into three groups (n = 6): Blank group, PCL/HA group, and PCL/HA/BMSCs group. Radiographic examination, histological, and histomorphometric analyses were performed to evaluate the result. In the blank group, the defect site couldn't maintain its original integrity due to no bone union. In the PCL/HA group and PCL/HA/BMSCs group, it was observed that the scaffolds retained their shapes without significant degradation at 12 weeks. Both groups could observe new bone-union by radiographic and histological examination. And PCL/HA/BMSCs would be more mineralized tissue area at implant sites (p < 0.05). These results reveal that using the FDM technique to manufacture the PCL/HA scaffolds with specific grooves could repair the sternal defect satisfactorily. Furthermore the scaffolds with BMSCs-seeded could enhance the amount of bone ingrowth and seemed to be more promising.

Effects of dietary energy and calcium levels on performance, egg shell quality and bone metabolism in hens.

This study investigated the effects of dietary energy and calcium levels on laying performance, eggshell quality and bone metabolism of layers. One hundred and sixty-two 19-week-old Hy-Line brown laying hens in 54 battery cages were allocated to one of nine dietary treatments with control, middle and high levels of energy (11.50, 12.68 and 13.37 MJ/kg, respectively) and low, control and high levels of calcium (2.62%, 3.7% and 4.4%, respectively) for 60 days, using a 3 × 3 factorial arrangement. Compared with the control energy diet, high- and middle-energy diets increased fat deposition and egg weight, decreased feed intake and bone quality and had no effects on eggshell quality. The high-energy diet reduced the serum phosphate concentration and elevated osteocalcin mRNA expression in the keel bone without increasing osteocalcin protein. Dietary calcium intake did not affect fat deposition, feed intake or egg weight. Low dietary calcium resulted in weaker eggshells and poorer bone quality than that from hens fed the control diet. High dietary calcium increased serum calcium concentration, osteoprotegerin mRNA and osteocalcin protein and inhibited serum alkaline phosphatase activity and decreased its mRNA compared with low or control dietary calcium. The high-energy and high-calcium diet significantly reduced egg production. Compared with the control energy diet, high- and middle-energy diets increased fat deposition but had negative effects on bone metabolic homeostasis. Dietary calcium did not influence fat deposition but a high-calcium diet benefited bone homeostasis, while a low-calcium diet was associated with poorer eggshell quality and bone homeostasis.

The analgesic effects of a bilateral sternal infusion of ropivacaine after cardiac surgery.

BACKGROUND AND OBJECTIVES: The aim of this study was to assess the effects of a continuous postoperative administration of local anesthetic through 2 catheters placed deeply under fascia at the lateral edges of the sternum, close to the emergence of the intercostal nerves. We focused on pain during mobilization, as this aspect is likely to interact with postoperative morbidity. METHODS: Forty adult patients scheduled for open heart surgery with sternotomy were included in this randomized, placebo-controlled, double-blind study. A continuous fixed-rate infusion of 4 mL/hr of 0.2% ropivacaine or normal saline was administered during the first 48 postoperative hrs. All patients received acetaminophen and self-administered morphine. The efficacy outcomes were as follows: pain score during standardized mobilization and at rest; morphine consumption; spirometry and arterial blood gases; postoperative rehabilitation criteria, and patient satisfaction. Total ropivacaine plasma level was monitored throughout the study. RESULTS: Pain scores were lower in the ropivacaine group during mobilization (P = 0.0004) and at rest (P = 0.0006), but the analgesic effects were mostly apparent during the second day after surgery, with a 41% overall reduction in movement-evoked pain levels. The bilateral sternal block also reduced morphine consumption. It improved the patients' satisfaction and rehabilitation, but no effects were noted on respiratory outcomes. No major adverse effect due to the treatment occurred, but the ropivacaine plasma level was greater than 4 mg/L in 1 patient. CONCLUSIONS: This technique may find a role within the framework of multimodal analgesia after sternotomy, although further confirmatory studies are needed.

Tocopherol succinate: modulation of antioxidant enzymes and oncogene expression, and hematopoietic recovery.

PURPOSE: A class of naturally occurring isoforms of tocopherol (tocols) was shown to have varying degrees of protection when administered before radiation exposure. We recently demonstrated that α-tocopherol succinate (TS) is a potential radiation prophylactic agent. Our objective in this study was to further investigate the mechanism of action of TS in mice exposed to (60)Co γ-radiation. METHODS AND MATERIALS: We evaluated the effects of TS on expression of antioxidant enzymes and oncogenes by quantitative RT-PCR in bone marrow cells of (60)Co γ-irradiated mice. Further, we tested the ability of TS to rescue and repopulate hematopoietic stem cells by analyzing bone marrow cellularity and spleen colony forming unit in spleen of TS-injected and irradiated mice. RESULTS: Our results demonstrate that TS modulated the expression of antioxidant enzymes and inhibited expression of oncogenes in irradiated mice at different time points. TS also increased colony forming unit-spleen numbers and bone marrow cellularity in irradiated mice. CONCLUSIONS: Results provide additional support for the observed radioprotective efficacy of TS and insight into mechanisms.

[Study on mutagenicity and teratogenicity of ammonium dinitramide].

OBJECTIVE: To study the mutagenicity and teratogenicity induced by ammonium dinitramide(ADN). METHODS: According to technical specifications for toxicity determination of chemicals, Salmonella typhimurium reverse mutation assay (Ames assay), in vivo mammalian erythrocyte micronucleus test, sperm malformation test and teratogenesis test were used to detect the mutagenicity and teratogenicity induced by AND. RESULTS: When the exposure doses of AND were 8-5000 pg/plate, the result of Ames assay was negative. As compared with control group, the micronucleus rate of mice exposed to 113.8 mg/kg AND significantly increased(P<0.05), the sperm malformation rates of mice exposed to 54.4-272.0 mg/kg AND did not increased significantly. The survival rate of fetuses decreased, the rate of assimilated fetuses increased, the rate of fetus sternum agenesis enhanced in mice exposed to 319 mg/kg AND, as compared with controls. The rates of in the 4th-6th fetus sternum agenesis in groups exposed to 21.3, 79.7 and 319 mg/kg AND were higher than that in control group. The malformation rate of fetus bowels in groups exposed to 319 mg/kg AND was higher than that in control group. The teratogenic index of ADN was 30. CONCLUSION: AND may be a mutagen and induce the teratogenic effect.

Self-limiting sternal tumors of childhood (SELSTOC).

BACKGROUND: Because a sternal mass is often alarming, it is important to identify the clinical features of benign processes. PROCEDURE: Data on clinical presentation, diagnostics, treatment and outcome of pediatric patients presenting with a sternal tumor between 2001 and 2009 were collected from medical records. RESULTS: Among the 1,700 children who were referred to our pediatric-oncology center, 14 presented with a rapidly growing sternal mass. All patients (10 males) were Caucasian and median age was 16 (range: 7-50) months. Reported symptoms were local pain (n = 7) and/or raised body temperature (n = 5). No major preceding traumas were reported. Physical examination revealed solid tumors with a median diameter of 3 (range: 1-4.5) cm in a pre-sternal/para-sternal location. Half of the patients showed red/blue discoloration of the skin. On radiology, dumbbell-shaped lesions extended to the area behind the sternal bone, involving the cartilage, leading to increased distance between ossification centers. Histopathology at diagnosis was available from five patients and showed aspecific chronic or acute inflammation (n = 4) and a reactive osteochondromatous lesion (n = 1). Laboratory infection parameters were not/only slightly raised and microbiologic cultures were negative in all patients. All tumors decreased in size within 1 month, in both patients with and without antibiotics. On physical examination the tumors disappeared within 6 months. CONCLUSIONS: This study reports 14 young children with a rapidly growing sternal mass due to aseptic inflammation, that we named self-limiting sternal tumor of childhood (SELSTOC). To prevent invasive diagnostic interventions and unnecessary treatment, we advocate a wait-and-see approach with close follow-up in the first weeks.