Damage to cellular DNA is believed determine the antiproliferative properties of platinum (Pt) drugs. This study characterized damage by oxaliplatin, a diaminocyclohexane Pt drug with clinical antitumor activity. Compared cisplatin, oxaliplatin formed significantly fewer Pt-DNA adducts (e.g., 0.86 ± 0.04 versus 1.36 0.01 adducts/10⁶ base pairs/10 μM drug/1 h, respectively, in CEM cells, <i>P</i> &lt; .01). Oxaliplatin was found induce potentially lethal bifunctional lesions, such...

Oxaliplatin is a clinical anticancer drug with pharmacological profile distinct from that of cisplatin. Our studies compared site- and region-specificity lesions induced by oxaliplatin cisplatin in naked intracellular DNA, respectively. adducts Simian virus 40 (SV40 DNA) were mapped repetitive primer extension. The sites nearly identical to the focused G clusters GNG motifs probably reflecting intrastrand cross-links. Although alkaline agarose electrophoresis specific SV40 fragments showed...

Allogeneic mesenchymal stem cells (MSCs) show great potential for the treatment of military and civilian trauma based on their reduced immunogenicity ability to modulate inflammation immune function in recipient. Although generally considered be safe, MSCs express tissue factor (TF), a potent activator coagulation. In current study, we evaluated multiple MSC populations expression procoagulant activity characterize safety considerations systemic use patients who may have altered coagulation...

Formulation of a medical preparedness plan for treating severely bleeding casualties during naval deployment is significant challenge because territory covered most missions. The aim this study was to evaluate the concept "walking blood bank" as supportable supplying safe and products.In 2013, Royal Norwegian Navy conducted antipiracy operations from frigate, beginning in Gulf Aden ending Indian Ocean. Crews were on 24-hour emergency alert preparation an enemy assault frigate. Under approved...

Several B2 bradykinin (BK) receptor-specific antagonists including HOE140, NPC17731, and NPC567 exhibited negative intrinsic activity, which was observed as a decrease in basal phosphoinositide hydrolysis primary cultures of rat myometrial cells, this response opposite to that elicited by the agonist BK. The order potency attenuating activity essentially same competing both [3H]BK [3H]NPC17731 for binding receptors on intact cells bovine membranes. We previously proposed three-state model...

Ordinarily, whole blood (WB) is separated into components before storage. We assessed the posttransfusion viability and function of platelets (PLTs) if they were stored within WB at 4°C.Whole was obtained from 30 normal subjects 4°C without agitation for 12 days 10, 15, or 22 with agitation. After storage, a PLT concentrate prepared, fresh sample each donor. The PLTs labeled 111 In 51 Cr, both simultaneously transfused their Blood samples after transfusion to determine recoveries survivals....

The role of transforming growth factor-beta (TGF-β) signaling in hepatocarcinogenesis remains controversial. We aimed to reveal TGF-β status human and murine tissues hepatocellular carcinoma (HCC) the mechanisms that mediate TGF-β's regulating HCC malignancy. Here, pathway component expression activation were measured with quantitative RT-PCR Western blotting assays. receptor Smad survival several cell lines was determined vitro vivo approaches. found II (TβRII) downregulated two different...

Multidrug-resistant Acinetobacter baumannii is among the most prevalent bacterial pathogens associated with trauma-related wound and bloodstream infections. Although septic shock disseminated intravascular coagulation have been reported following fulminant A. sepsis, little known about protective host immune response to this pathogen. In study, we examined role of PTX3, a soluble pattern recognition receptor antimicrobial properties stored within neutrophil granules. PTX3 production by...

Rationale: Early post injury mitigation strategies in ARDS are short supply. Treatments with allogeneic stromal cells administered after develops, require specialized expertise and equipment, to date have shown limited benefit. Objectives: Assess the efficacy of immediate intravenous administration autologous or bone marrow–derived mesenchymal (MSCs) for treatment acute respiratory distress syndrome (ARDS) due smoke inhalation burns. Methods: Yorkshire swine (n = 32, 44.3 ± 0.5 kg) underwent...

Chemical cross-linking combined with site-directed mutagenesis was used to evaluate the role of extracellular cysteines and their positions relative binding site for agonist bradykinin (BK) in human BK B2 receptor. All cysteines, Cys20, Cys103, Cys184, Cys277, receptor were mutated serines, single double mutants transfected into COS-7 cells. The Ser20 Ser277 Ser20/Ser277 mutant bound [3H]BK antagonist [3H]NPC17731 pharmacological profiles identical wild-type In contrast, Ser103 Ser184 unable...

Objectives: Autotransfusion of shed blood from traumatic hemothorax is an attractive option for resuscitation trauma patients in austere environments. However, previous analyses revealed that (HX) defibrinated, thrombocytopenic, and contains elevated levels D-dimer. Mixing studies with normal pooled plasma demonstrated hypercoagulability, evoking concern potentiation acute coagulopathy. We hypothesized induction coagulopathic changes by HX may be due to increases cellular microparticles (MP)...

Chemical cross-linking was used to analyze the binding sites for agonist bradykinin (BK) and antagonists NPC17731 HOE140 on bovine B2 receptor. [3H]BK [3H]NPC17731 bound with high affinity same receptor in myometrial membranes as determined by total number of specific pharmacological specificity these two radioligands. Cross-linking experiments were done using a series bifunctional reagents reactive either primarily amines (homobifunctional) or one end sulfhydryls opposite...

Stem cells derived from the subcutaneous adipose tissue of debrided burned skin represent an appealing source adipose-derived stem (ASCs) for regenerative medicine. Traditional culture uses fetal bovine serum (FBS), which complicates utilization ASCs in human Human platelet lysate (hPL) is one potential xeno-free, alternative supplement use ASC culture. In this study, adipogenic and osteogenic differentiation media supplemented with 10% FBS or hPL was compared abdominoplasty (HAP) associated...

BACKGROUND Cellular therapeutic agents may benefit trauma patients by modulating the immune response to injury, and reducing inflammation vascular leakage. Administration of allogeneic mesenchymal stromal cells (MSCs) shows some in preclinical clinical trials, but less testing has been performed with other cell types. Human primary fibroblasts (FBs) were compared MSCs assays designed evaluate determine if these actually properties unique or whether related types perform similarly. STUDY...

Trauma patients are susceptible to coagulopathy and dysfunctional immune responses. Mesenchymal stromal cells (MSCs) at the forefront of cellular therapy revolution with profound immunomodulatory, regenerative, therapeutic potential. Routine assays assess immunomodulation activity examine MSC effects on proliferation peripheral blood mononuclear (PBMCs) take 3-7 days. Assays that could be done in a shorter period time would beneficial allow more rapid comparison different donors. The studies...

Smoke inhalation and burn injury remain a major source of morbidity mortality. There is known dysregulation hemostasis in patients, but either hypercoagulation or hypocoagulation states are reported. Sheep an established animal model for studying pathology provide robust data on hemostatic function at baseline after injury.After IACUC-approved protocol, 15 sheep were anesthetized subjected to 40% full thickness with smoke inhalation. Blood was sampled baseline, 1 day postinjury (early...