Comparison of tranexamic acid plasma concentrations when administered via intraosseous and intravenous routes.

INTRODUCTION: There is a lack of information regarding intraosseous (IO) administration of tranexamic acid (TXA). Our hypothesis was that a single bolus IO injection of TXA will have a similar pharmacokinetic profile to TXA administered at the same dose IV. METHODS: Sixteen male Landrace cross swine (mean body weight 27.6±2.6kg) were divided into an IV group (n=8) and an IO group (n=8). Each animal received 30mg/kg TXA via an IV or IO catheter, respectively. Jugular blood samples were collected for pharmacokinetic analysis over a 3h period. The maximum TXA plasma concentration (Cmax) and corresponding time as well as distribution half-life, elimination half-life, area under the curve, plasma clearance and volume of distribution were calculated. One- and two-way analysis of variance for repeated measures (time, group) with Tukey's and Bonferonni post hoc tests were used to compare TXA plasma concentrations within and between groups, respectively. RESULTS: Plasma concentrations of TXA were significantly higher (p<0.0001) in the IV group during the TXA infusion. Cmax occurred at 4min after initiation of the bolus in the IV group (9.36±3.20ng/µl) and at 5min after initiation of the bolus in the IO group (4.46±0.49ng/µl). Plasma concentrations were very similar from the completion of injection onwards. There were no significant differences between the two administration routes for any other pharmacokinetic variables measured. CONCLUSION: The results of this study support pharmacokinetic bioequivalence of IO and IV administration of TXA.

Protective effects of N-methyl-D-aspartate receptor antagonism on VX-induced neuronal cell death in cultured rat cortical neurons.

Exposure of the central nervous system to organophosphorus (OP) nerve agents induces seizures and neuronal cell death. Here we report that the OP nerve agent, VX, induces apoptotic-like cell death in cultured rat cortical neurons. The VX effects on neurons were concentration-dependent, with an IC(50) of approximately 30 microM. Blockade of N-methyl-D-aspartate receptors (NMDAR) with 50 microM. D-2-amino-5-phosphonovalerate (APV) diminished 30 microM VX-induced total cell death, as assessed by alamarBlue assay and Hoechst staining. In contrast, neither antagonists of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) nor metabotropic glutamate receptors (mGluRs) had any effect on VX-induced neurotoxicity. VX-induced neuronal cell death could not be solely attributed to acetylcholinesterase (AChE) inhibition, since neither the reversible pharmacological cholinesterase inhibitor, physostigmine, nor the muscarinic receptor antagonist, atropine, affected VX-induced cell death. Importantly, APV was found to be therapeutically effective against VX-induced cell death up to 2 h post VX exposure. These results suggest that NMDARs, but not AMPARs or mGluRs, play important roles in VX-induced cell death in cultured rat cortical neurons. Based on their therapeutic effects, NMDAR antagonists may be beneficial in the treatment of VX-induced neurotoxicities.

Effects of topical elk velvet antler on cutaneous wound healing in streptozotocin-induced diabetic rats.

OBJECTIVE: Wound repair is a finely orchestrated process involving cellular, molecular, physiologic, and biochemical interactions that restore the integrity of damaged tissue. Cyclic replacement of deer antlers requires rapid regenerative growth, in many ways analogous to that encountered during tissue repair. Molecular mechanisms regulating these processes are not fully understood, but it is increasingly apparent that growth factors are important mediators. Previous studies have shown that elk velvet antler (EVA) contains various growth factors and that a water-soluble extract stimulates dermal fibroblast growth in vitro. DESIGN: The efficacy of EVA water-soluble extract on wound healing in streptozotocin-induced diabetic rats was EVAluated using a full-thickness cutaneous wound model. Animals were randomly selected to receive topical application of either control or EVA gel. Daily photographs of the wounds served to measure the rate of wound closure. Wound-edge biopsies obtained on postoperative days 2 and 10 allowed histologic evaluation and measurement of transforming growth factor-beta 1 (TGF-beta (1)) concentrations by enzyme-linked immunoabsorbent assay. RESULTS: Wounds treated with the EVA topical gel were significantly smaller by postoperative day 6. TGF- beta (1) protein expression was not different in EVA-treated wounds compared to control wounds. CONCLUSIONS: This study indicates that topical treatment with an EVA water-soluble extract accelerates repair of cutaneous wounds in diabetic rats. Further studies are warranted to reveal the mechanisms involved in EVA enhancement of wound closure and to determine if this compound is an economical pharmacologic agent in the treatment of normal and compromised wounds.

Neuroleptic malignant syndrome: case report and discussion.

We report a case involving an 81-tear-old man with schizoaffective disorder who presented with neuroleptic malignant syndrome (NMS) after an increase in his neuroleptic dose. NMS, a rare but potentially fatal complication of neuroleptic medications (e.g., antipsychotics, sedatives and antinauseants), is characterized by hyperthermia, muscle rigidity, an elevated creatine kinase level and autonomic instability. The syndrome often develops after a sudden increase in dosage of the neuroleptic medication or in states of dehydration. Treatment is mainly supportive and includes withdrawal of the neuroleptic medication and, possibly, administration of drugs such as dantrolene and bromocriptine. Complications of NMS include acute renal failure and acute respiratory failure. Given the widespread prescription of neuroleptics by physicians in a variety of fields, all physicians need to be able to recognize and appropriately manage NMS.