Effect of the free radical scavenger MCI-186 on spinal cord reperfusion after transient ischemia in the rabbit

Objective: Paraplegia remains a serious complication of aortic operations. The production of free radicals during reperfusion after transient ischemia is believed to induce secondary spinal neuronal injury, resulting in paraplegia. The aim of the present study was to clarify the protective effect and method of administration of antioxidants on the neurological and histological outcome in the animal model for reperfusion injury after transient spinal cord ischemia. Methods: New Zealand white rabbits underwent surgical exposure of the abdominal aorta that was clamped for 15 minutes to achieve spinal cord ischemia. Group A animals received two 10 mg/kg doses of 3-methyl-l-phenyl-2-pyrazolin-5-one (MCI-186) at the time of release of the aortic clamp and 30 minutes later. In group B, MCI-186, 5 mg/kg, was given three times, at the time of aorta clamp release, 30 minutes and 12 hours later. In group C (control group), one dose of vehicle was administered. Neurological status was assessed using modified Tarlov’s score until 168 hours after operation. Spinal cord sections were examined microscopically to determine the extent of ischemic neuronal damage. Results: Groups A and B animals had better neurological function than group C (p(0.001). In contrast, group C animals exhibited paraplegia or paraparesis with marked neuronal necrosis. The number of surviving neurons within examined sections of the spinal cord was significantly greater in group B than in group C (p(0.001). Conclusion: In a 15-minute ischemia-reperfusion model using rabbits, systemic repetitious administration of MCI-186, a free radical scavenger, was found to have a protective effect on the spinal cord neurons both neurologically and histologically. We postulate that the drug minimizes the delayed neuronal cell death for reperfusion injury after transient ischemia by reducing the free radical molecules. Moreover, it was thought that we could protect delayed neuronal cell death more effectively by administering MCI-18612 hours later.     

Pharyngeal Patency in Response to Advancement of the Mandible in Obese Anesthetized Persons

Background: During anesthesia in humans, anterior displacement of the mandible is often helpful to relieve airway obstruction. However, it appears to be less useful in obese patients. The authors tested the possibility that obesity limits the effectiveness of the maneuver.

Methods: Total muscle paralysis was induced under general anesthesia in a group of obese persons (n = 9; body mass index, 32 +/- 3 kg sup -2) and in a group of nonobese persons (n = 9; body mas index, 21 +/- 2 kg sup -2). Nocturnal oximetry confirmed that none of them had sleep-disordered breathing. The cross-sectional area of the pharynx was measured endoscopically at different static airway pressures. A static pressure-area plot allowed assessment of the mechanical properties of the pharynx. The influence of mandibular advancement on airway patency was assessed by comparing the static pressure-area relation with and without the maneuver in obese and nonobese persons.

Results: Mandibular advancement increased the retroglossal area at a given pharyngeal pressure, and mandibular advancement increased the retropalatal area in nonobese but not in obese persons at a given pharyngeal pressure.     

In vivo evaluation of expressed protein function by PET]

Positron Emission Tomography (PET) allows in vivo visualization of the expression and function of protein using a radioligand. Quantitative analysis of serotonin transporter, receptors, and the function of P-Glycoprotein has been performed in living human brains. Furthermore, the relationship between the phenotype of those proteins and their genetic polymorphism has also been investigated. Regarding the effect of antipsychotics on dopamine D2 receptor, occupancy and its time-course have been measured in a living body using PET. This approach can provide in vivo pharmacological evidences of antipsychotics and establish a rational therapeutic strategy. PET is a powerful tool not only in the field of brain research but also drug discovery and individual medicine.     

Enhancing Effects of Harman and Norharman on Induction of Preneoplastic and Neoplastic Kidney Lesions in Rats Initiated with N-Ethyl-N-hydroxyethylnitrosamine

The modifying potential of two nephrotoxic agents, harman and norharman, on N-ethyl-N-hydroxyethylnitrosamine (EHEN)-induced renal and hepatic carcinogenesis was investigated in male F344/DuCrj rats. Animals were given 0.1% EHEN in their drinking water for the first 2 weeks as an initiator. Subsequently, starting 3 weeks from the commencement, they were fed diet containing these compounds at concentrations of 1000, S00 or 0 ppm until week 26, and then killed for light microscopic examination. The mean numbers of renal tubular cell hyperplasias/cm² and those of tumors/cm² in rats given harman and norharman at 1000 ppm after initiation, but not at 500 ppm, were significantly increased as compared to the control values. However, neither compound modified liver carcinogenesis. It is concluded that harman and norharman show enhancing effects on rat kidney carcinogenesis, when ingested at dose levels which cause renal tubular damage.     

Influence of acetylcholine on neuronal activity of monkey amygdala during bar press feeding behavior

Single neuron activity in the monkey amygdala was investigated during cue signalled conditioned bar press feeding behavior and the effects of electrophoretically applied acetylcholine (ACh) and atropine were analyzed. ACh increased the firing rate of one third of the neurons tested; these excitatory responses were inhibited by the muscarinic receptor antagonist atropine. No characteristic location of ACh-sensitive neurons was found, cells were diffusely distributed throughout the amygdala. Activity of ACh-sensitive neurons did not correlate with any particular event during the bar press feeding task. However, continuous application of ACh at low current intensity during the task significantly enhanced the task-related excitatory firing patterns, or markedly attenuated the inhibitory responses. Continuous application of atropine elicited or enhanced inhibitory response patterns. These results suggest that the cholinergic system of the monkey amygdala facilitates neuronal excitation but attenuates inhibition related to various phases of feeding behavior, such as to cue recognition, food aquisition and rewarding process.     

Laryngeal Resistance before and after Minor Surgery: Endotracheal Tube versus Laryngeal Mask Airway™

Background: The placement of an endotracheal tube (ETT) may promote laryngeal swelling, which is an important cause of upper airway obstruction after extubation. The authors hypothesized that laryngeal swelling after ETT placement increases laryngeal resistance and tested that hypothesis by comparing postoperative laryngeal patency between patients with ETT placement and those with a Laryngeal Mask Airway(TM) (LMA(TM)).

Methods: Fourteen adult patients who underwent elective minor surgeries were randomly allocated to two groups whose airway would be managed through ETTs (the ETT group) or LMAs(TM) (the LMA(TM) group) during the surgery. While maintaining at sevoflurane 1 minimum alveolar concentration, the authors measured laryngeal resistance before and after surgery, during both spontaneous breathing and mechanical ventilation under complete paralysis. In addition, they endoscopically measured the vocal cord angle under complete paralysis.

Results: In association with marked swelling of the vocal cords, the vocal cord angle significantly decreased after surgery in the ETT group, whereas the angle did not change in the LMA group. Laryngeal resistance during mechanical ventilation significantly increased only in the ETT group. Laryngeal resistance during spontaneous breathing significantly increased after surgeries in both groups.     

INTRAOPERATIVE BLEEDING IN ENDOSCOPIC SUBMUCOSAL DISSECTION IN THE STOMACH AND STRATEGY FOR PREVENTION AND TREATMENT

To control intraoperative bleeding is an important key to successful endoscopic submucosal dissection. The distribution of submucosal vessels encountered during the procedure differ in places in the stomach and are roughly categorized into three groups: those located in the antrum, those in the lesser curvature, and those on the anteroposterior corpus wall which consists of oblique muscle layers. Therefore, knowledge of a suitable setting of diathermy and adjusted depth of dissection in the submucosal layer for each site is imperative. The combination of utilizing the distal attachment forced or swift coagulation (trimming with coagulation mode) have enable the treatment with an insulation tipped knife safer.