Liver Transplant Education and Training for Medical Surgical ICU Nurses

This project focuses on the CNL curriculum element of Nursing Leadership and explores the need for appropriate education and training for liver transplant as a new patient population for Medical Surgical ICU nurses. The transplant experience for these nurses currently include critically ill Bone Marrow Transplant, as well as stable heart and lunch transplant. The methods used to implement the project were to develop an education curriculum, a clinical orientation program, and a process to ensure proper communication occurs between all parties prior to clinical orientation. The competency-based orientation document, which is still being drafted, is used to determine clinical competency. Although the education and training will be ongoing, 22 nurses are expected to be considered competent by the completion of this project. As of the time of this writing, 50 nurses have attended the liver transplant education class with another 12 registered for the final summer class. A pre-test was completed prior to the class by all registrants, while only 15 nurses have completed the post-test and six nurses have obtained some clinical orientation. This paper reviews articles published on nursing care immediately post operation, education and learning methods, and effectiveness of structured orientation

Inquiries into Wheat Streak Mosaic Virus and Other WSM Associated Viruses

Wheat Streak Mosaic WSM) is a complex disease found to cause severe impact on wheat yield. Wheat streak mosaic virus (WSMV Triticum Mosaic Virus (TMV) and Wheat Mosaic Virus (WMOV) are all transmitted by Aceria tosichella, the wheat cun mite, and have been reported as the viruses associated with WSM. There is a research project on the genetic composition of the associated viruses as well as determining any novel viruses that may be involved in the disease. The process has begun with the virus assessment of neid samples by RT-PCR and sanger Sequencing in a different study, the potential of a common Insect in wheat fields. Rhopalosiphum padi, the Bird cherry oat aphid, to be a vector for WSMV was Investigated. R. Daar was found to be not a vector of WSMV through RT-PCR. The other proiect screened some wid-relative wheat plants for WSMV resistance Various lines of Aeglos tauschii, a landrace wheat, were tested for viral resistance by assessing the viral copy number by RT-PCR. The Initial result has demonstrated that one of the four selected lines may have promising tolerance The preliminary tests performed for each Inquiry provides Insight to Improving the respective experiment design for further understanding of how concerned parties such as farmers may better combat the disease

Effects of acetaldehyde, GABAergic, and glutamatergic manipulation on an ethanol discriminative taste aversion

The primary objective of the present thesis was to examine the contribution of acetaldehyde, as well as GABA receptor agonists and glutamate receptor antagonists in mediating the discriminative stimulus effects of ethanol using a discriminative taste aversion (DTA) procedure. The DTA procedure trained animals to associate the stimulus effects of ethanol or acetaldehyde with either a saccharin-LiCl or a saccharin-saline pairing. Animals in the LiCl group learned to decrease their saccharin intake following ethanol or acetaldehyde injections but not after saline injections. Animals in the Saline groups did not decrease their saccharin intake when injected with either the training drug or saline. Experiment 1 a showed that acetaldehyde partially substituted for ethanol while experiment 1b showed that ethanol partially substituted for acetaldehyde. Administration of the catalase inhibitor aminotriazole failed to block the discriminative cue of ethanol. Animals in experiment 2 and 3 were trained to discriminate ethanol from saline. Generalization tests showed that administration of the gamma-aminotransaminase inhibitor AOAA, the GABA A agonists THIP and pentobarbital, the GABA B agonist baclofen failed to substitute for ethanol while the GABA A antagonist picrotoxin failed to block the ethanol cue. Experiment 3 showed that the NMDA antagonists MK-801 and memantine substituted for ethanol while the AMPA antagonist GYKI 52466 did not, suggesting that inhibition of the NMDA receptor, but not the AMPA receptor contributes to the stimulus effects of ethanol. Overall, the findings from the present thesis showed that the DTA procedure could quickly and reliably train animals to discriminate ethanol, and acetaldehyde, from saline. Generalization tests demonstrated that acetaldehyde and the NMDA receptor, but not the GABA A receptor, contributes to the stimulus effects of ethanol

An examination of the effects of the catalase inhibitor 3-amino-1,2,4-triazole on ethanol, food and water intake

The effects of the catalase inhibitor 3-amino-1,2,4-triazole (AT) were examined on ethanol, food and water intakes to determine if it produced a decrease in ethanol consumption through the decrease in catalase produced acetaldehyde or to a general decrease in caloric intake. Experiment 1A demonstrated that a food containing a concentration of 0.6% w/w sodium saccharin was preferred over a neutral-flavoured food while a concentration of 0.15% w/w of quinine sulfate was less preferred. These two concentrations of saccharin and quinine were used in experiment 1B to study the effects of AT on taste reactivity. Results of experiment 1B showed that AT significantly decreased food intake but not ethanol water or total fluid intakes. The saccharin, neutral and quinine food groups decreased their food intakes to the same extent suggesting that AT did not affect taste reactivity. Furthermore, quinine-fed rats significantly increased their ethanol consumption while decreasing their food and water intakes. Experiment 1C tested whether the quinine-induced changes in ethanol, food and water intakes were mediated through the 5-\rm HT\sb2 receptor. The 5-\rm HT\sb2 antagonist ritanserin failed to attenuate the quinine-induced ethanol consumption or to affect food or water intakes. Experiment 2 showed that AT significantly decreased ethanol consumption but did not significantly affect either food or water intake. Taken together, the findings of experiments 1B and 2 demonstrated that AT does not produce a general decrease in the caloric requirement of the animal. The failure of AT to decrease ethanol consumption in experiment 1B is contradictory to previous reports regarding the role of catalase produced acetaldehyde and its role in the mediation of ethanol intake. However, the decrease in ethanol intake observed in experiment 2 is consistent with the pattern of catalase inhibition suggesting that acetaldehyde may be involved in the mediation of voluntary ethanol consumption

Effects of acetaldehyde, GABAergic, and glutamatergic manipulation on an ethanol discriminative taste aversion

The primary objective of the present thesis was to examine the contribution of acetaldehyde, as well as GABA receptor agonists and glutamate receptor antagonists in mediating the discriminative stimulus effects of ethanol using a discriminative taste aversion (DTA) procedure. The DTA procedure trained animals to associate the stimulus effects of ethanol or acetaldehyde with either a saccharin-LiCl or a saccharin-saline pairing. Animals in the LiCl group learned to decrease their saccharin intake following ethanol or acetaldehyde injections but not after saline injections. Animals in the Saline groups did not decrease their saccharin intake when injected with either the training drug or saline. Experiment 1 a showed that acetaldehyde partially substituted for ethanol while experiment 1b showed that ethanol partially substituted for acetaldehyde. Administration of the catalase inhibitor aminotriazole failed to block the discriminative cue of ethanol. Animals in experiment 2 and 3 were trained to discriminate ethanol from saline. Generalization tests showed that administration of the gamma-aminotransaminase inhibitor AOAA, the GABA A agonists THIP and pentobarbital, the GABA B agonist baclofen failed to substitute for ethanol while the GABA A antagonist picrotoxin failed to block the ethanol cue. Experiment 3 showed that the NMDA antagonists MK-801 and memantine substituted for ethanol while the AMPA antagonist GYKI 52466 did not, suggesting that inhibition of the NMDA receptor, but not the AMPA receptor contributes to the stimulus effects of ethanol. Overall, the findings from the present thesis showed that the DTA procedure could quickly and reliably train animals to discriminate ethanol, and acetaldehyde, from saline. Generalization tests demonstrated that acetaldehyde and the NMDA receptor, but not the GABA A receptor, contributes to the stimulus effects of ethanol

ORC-13661 protects sensory hair cells from aminoglycoside and cisplatin ototoxicity

Aminoglycoside (AG) antibiotics are widely used to prevent life-threatening infections, and cisplatin is used in the treatment of various cancers, but both are ototoxic and result in loss of sensory hair cells from the inner ear. ORC-13661 is a new drug that was derived from PROTO-1, a compound first identified as protective in a large-scale screen utilizing hair cells in the lateral line organs of zebrafish larvae. Here, we demonstrate, in zebrafish larvae and in mouse cochlear cultures, that ORC-13661 provides robust protection of hair cells against both ototoxins, the AGs and cisplatin. ORC-13661 also prevents both hearing loss in a dose-dependent manner in rats treated with amikacin and the loading of neomycin-Texas Red into lateral line hair cells. In addition, patch-clamp recordings in mouse cochlear cultures reveal that ORC-13661 is a high-affinity permeant blocker of the mechanoelectrical transducer (MET) channel in outer hair cells, suggesting that it may reduce the toxicity of AGs by directly competing for entry at the level of the MET channel and of cisplatin by a MET-dependent mechanism. ORC-13661 is therefore a promising and versatile protectant that reversibly blocks the hair cell MET channel and operates across multiple species and toxins

An in vivo Biomarker to Characterize Ototoxic Compounds and Novel Protective Therapeutics

There are no approved therapeutics for the prevention of hearing loss and vestibular dysfunction from drugs like aminoglycoside antibiotics. While the mechanisms underlying aminoglycoside ototoxicity remain unresolved, there is considerable evidence that aminoglycosides enter inner ear mechanosensory hair cells through the mechanoelectrical transduction (MET) channel. Inhibition of MET-dependent uptake with small molecules or modified aminoglycosides is a promising otoprotective strategy. To better characterize mammalian ototoxicity and aid in the translation of emerging therapeutics, a biomarker is needed. In the present study we propose that neonatal mice systemically injected with the aminoglycosides G418 conjugated to Texas Red (G418-TR) can be used as a histologic biomarker to characterize in vivo aminoglycoside toxicity. We demonstrate that postnatal day 5 mice, like older mice with functional hearing, show uptake and retention of G418-TR in cochlear hair cells following systemic injection. When we compare G418-TR uptake in other tissues, we find that kidney proximal tubule cells show similar retention. Using ORC-13661, an investigational hearing protection drug, we demonstrate in vivo inhibition of aminoglycoside uptake in mammalian hair cells. This work establishes how systemically administered fluorescently labeled ototoxins in the neonatal mouse can reveal important details about ototoxic drugs and protective therapeutics

Involvement of Noradrenergic Neurotransmission in the Stress- but not Cocaine-Induced Reinstatement of Extinguished Cocaine-Induced Conditioned Place Preference in Mice: Role for β-2 Adrenergic Receptors

The responsiveness of central noradrenergic systems to stressors and cocaine poses norepinephrine as a potential common mechanism through which drug re-exposure and stressful stimuli promote relapse. This study investigated the role of noradrenergic systems in the reinstatement of extinguished cocaine-induced conditioned place preference by cocaine and stress in male C57BL/6 mice. Cocaine- (15 mg/kg, i.p.) induced conditioned place preference was extinguished by repeated exposure to the apparatus in the absence of drug and reestablished by a cocaine challenge (15 mg/kg), exposure to a stressor (6-min forced swim (FS); 20–25°C water), or administration of the α-2 adrenergic receptor (AR) antagonists yohimbine (2 mg/kg, i.p.) or BRL44408 (5, 10 mg/kg, i.p.). To investigate the role of ARs, mice were administered the nonselective β-AR antagonist, propranolol (5, 10 mg/kg, i.p.), the α-1 AR antagonist, prazosin (1, 2 mg/kg, i.p.), or the α-2 AR agonist, clonidine (0.03, 0.3 mg/kg, i.p.) before reinstatement testing. Clonidine, prazosin, and propranolol failed to block cocaine-induced reinstatement. The low (0.03 mg/kg) but not high (0.3 mg/kg) clonidine dose fully blocked FS-induced reinstatement but not reinstatement by yohimbine. Propranolol, but not prazosin, blocked reinstatement by both yohimbine and FS, suggesting the involvement of β-ARs. The β-2 AR antagonist ICI-118551 (1 mg/kg, i.p.), but not the β-1 AR antagonist betaxolol (10 mg/kg, i.p.), also blocked FS-induced reinstatement. These findings suggest that stress-induced reinstatement requires noradrenergic signaling through β-2 ARs and that cocaine-induced reinstatement does not require AR activation, even though stimulation of central noradrenergic neurotransmission is sufficient to reinstate