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The name of Keizo Uenaka has not been documented in textbooks. However, Uenaka was the scientist who worked on ephedrine and played a practical role in the purification and crystallization of adrenaline. His handwritten memorandum, "On Adrenaline, Memorandum, July to December, 1900" is now stored in a Buddhist temple, Kyougyou-ji in Nashio, Japan. In the present report, we compared Uenaka's original description and Jokichi Takamine's published scientific reports, and examined how each statement in four documents are related to each other in terms of successful adrenaline crystallization. Uenaka's memorandum contained precise procedures and experimental tips for successful purification. The experimental steps were considered to transcribed in the first published document in The American Journal of Pharmacy by Takamine in 1901, and summarized in another document in ``Journal of Physiology'' in 1901. A Japanese version was published in ``Yakugakuzasshi'' in 1903 by translating the English paper in the American Journal of Pharmacy published in 1901. Reading Uenaka's memorandum, we realized that he tirelessly and diligently undertook routine experiments that to some of us might seem boring and laborious. Although the name of Uenaka is not globally well known, he was the main scientist who did the actual work of purifying adrenaline.

DDHD2 has been reported to exhibit phospholipase A1, triacylglycerol (TG) lipase and diacylglycerol (DG) lipase activities. However, the detailed enzymatic properties of DDHD2 have not yet been elucidated. In the current study, the substrate specificity of DDHD2 towards DG, TG and phosphatidic acid (PA) has been examined using highly purified recombinant rat DDHD2 (rDDHD2) with a liquid chromatography mass spectrometer. The k cat/Km value for DG (18:0/20:4) was much higher than those for TG (18:1/18:1/18:1), and PA (18:0/20:4) in the presence of sodium deoxycholate. The enzyme activity of rDDHD2 towards DG (18:0/20:4) was highest among all of the substrates tested. In addition, rDDHD2 was highly specific to DG substrates with a polyunsaturated fatty acid at their sn-2 position. The levels of 2-arachidonoylglycerol (2-AG) in CHO cells were quantified by gas chromatography-tandem mass spectrometry, showing that CHO cells expressing recombinant rDDHD2 contained higher levels of 2-AG when cells were treated with a monoacylglycerol lipase inhibitor, URB602. These results therefore support the idea that DDHD2 functions as a DG lipase in vivo and produces 2-AG.

Cannabis has a detrimental impact on the developing nervous system. Therefore, regular con- sumption of cannabis by pregnant and lactating woman poses a potential risk to neuronal growth in fetuses and infants. Indeed, endogenous cannabis-like molecules called endocannabinoids re- gulate many physiological processes, including neurogenesis, axon guidance, and synaptic plastic- ity through CB1 receptors. To investigate the physiological role of CB1 receptors on peripheral sensory nerve growth, the endocannabinoid 2-arachidonoyl glycerol was added to cultured chick dorsal root ganglion neurons. This compound inhibited neurite elongation and induced growth cone collapse in a dose- and time-dependent manner. These data suggest that caution should be exercised regarding maternal cannabis use during pregnancy. Because ectopic sprouting and ab- normal neuronal network connections are considered to be a cause of neuropathic pain, our cur- rent data imply an additional role of endocannabinoids as inhibitors of the formation of pain- maintenance networks.

Supplementation with oxygen is fundamental in rescue and emergency medicine. However, transportation of oxygen cylinders or a rigid hyperbaric chamber requires large work forces. Also, oxygen in a cylinder may be completely consumed during a rescue action. The oxygen concentrators, which enrich the oxygen percentage of ambient air, may free rescuers from carrying heavy oxygen cylinders. In the present study, 2 types of oxygen concentrators were tested in a mountain hut located at an altitude of 3776 m. Oxygen concentration of the generated gas was 28.6% +/- 0.8% with the first machine, which was powered by an internal battery. Arterial oxygen saturation of the volunteers inhaling through the machine increased from the original 79% +/- 6% to 82% +/- 6%. When the machine was used with a semi-closed circuit, the value increased further to 90% +/- 3%. The second concentrator, which was powered by an external electric generator, outputted 90% +/- 2% oxygen. Arterial oxygen saturation of the volunteers increased to 95% +/- 1%. It is concluded that both types of oxygen concentrators were efficient at high altitude.

Diacylglycerol (DG) lipase, which hydrolyses 1-stearoyl-2-arachidonyl-sn-glycerol to produce an endocannabinoid, 2-arachidonoylglycerol, was purified from the soluble fraction of rat brain lysates. DG lipase was purified about 1,200-fold by a sequential column chromatographic procedure. Among proteins identified by mass spectrometry analysis in the partially purified DG lipase sample, only DDHD domain containing two (DDHD2), which was formerly regarded as a phospholipase A1, exhibited significant DG lipase activity. Rat DDHD2 expressed in Chinese hamster ovary cells showed similar enzymatic properties to partially purified DG lipase from rat brain. The source of DG lipase activity in rat brain was immunoprecipitated using anti-DDHD2 antibody. Thus, we concluded that the DG lipase activity in the soluble fraction of rat brain is derived from DDHD2. DDHD2 is distributed widely in the rat brain. Immunohistochemical analysis revealed that DDHD2 is expressed in hippocampal neurons, but not in glia.

The number of alpine accidents has markedly increased among elderly trekkers in an aging society, Japan. We evaluated the physical condition of 176 trekkers by interview and physical examination on a popular middle altitude mountain. Heart rate, noninvasive blood pressure and arterial oxygen saturation (SpO2) were measured using a portable life monitor. It was revealed that more than 70% of the trekkers were over 50. Seventy-five percent of trekkers over 70 had some pre-existing medical problems. Systolic and diastolic blood pressure before the start of trekking, increased with age. However, such age-dependent differences were not apparent at the summit hut. SpO2 values decreased slightly but significantly with age. In conclusion, many elderly people enjoy nonchallenging middle altitude trekking in an aging society. Alpine accidents caused by health problems tend to arise more frequently in this population. Alpine rescue teams should be well-prepared for the alpine accidents of elderly trekkers.

The pathophysiology of altitude-related disorders in untrained trekkers has not been clarified. In the present study, the effects of workload on cardiovascular parameters and regional cerebral oxygenation were studied in untrained trekkers at altitudes of 2700 m and 3700 m above sea level. We studied 6 males and 4 females at each altitude, and their average ages were 31.3+/-7.1 y at 2700 m and 31.2+/-6.8 y at 3700 m, respectively. The resting values of heart rate and mean blood pressure were not significantly different at 2700 m and 3700 m than at sea level. However, increases in these values after exercise were more prominent at high altitudes (heart rate increase = 51.6% at 2700 m and 70.4% at 3700 m; mean blood pressure increase: 19.0% at 2700 m and 17.2% at 3700 m). In addition, post-exercise blood lactate concentration was significantly higher at 3700 m than at sea level or at 2700 m (i.e., 7.6 mM at 3700 m, 3.8 mM at 2700 m, and 4.17 mM at 0 m, respectively). Exercise induced an acute reduction in the arterial oxygen saturation value (SpO2) at 2700 m and 3700 m (i.e., 11.2% reduction at 2700 m and 9.4% at 3700 m), whereas no changes were observed at sea level. The resting values of regional oxygen saturation (rSO2)--measured by a near infra-red spectrophotometer at sea level, 2700 m, and 3700 m-were nearly identical. Exercise at sea level did not reduce this value. In contrast, we observed a decrease in rSO2 after subjects exercised at 2700 m and 3700 m (i.e., 26.9% at 2700 m and 48.1% at 3700 m, respectively). The rSO2 measured 2 min and 3 min after exercise at 3700 m was significantly higher than the preexercise value. From these observations, we concluded that alterations in cardiovascular parameters were apparent only after an exercise load occurred at approximately 3000 m altitude. Acute reduction in cerebral regional oxygen saturation might be a primary cause of headache and acute mountain sickness among unacclimatized trekkers.

Background: It is well known that patients undergoing shoulder surgery in the Beach Chair Position (BCP) have a potential risk for cerebral ischemia. Using Near-Infrared Spectroscopy (NIRS), this study aimed to test whether cerebral oxygenation in these patients was impaired by brachial plexus block accompanied with general anesthesia. Methods: Ultrasound-guided interscalene brachial plexus block was performed in 26 patients undergoing elective arthroscopic shoulder surgery under general anesthesia. In all subjects, cerebral oxygenation during anesthesia was evaluated by measuring the Tissue Oxygenation Index (TOI) with NIRS. Results: No differences were seen in TOI values between Pre-BCP and Post-BCP periods in both block and non-block sides, despite a decrease in mean blood pressure (P

The authors experienced a case of prolonged cardiopulmonary resuscitation (CPR) on Mount Fuji (3776 m) that demanded strenuous work by the rescuers. The objective of this study was to provide information regarding the physiologic effects on the rescuers of performing CPR at moderate altitude.The effects of CPR at 2700 m and 3700 m above sea level on the physical condition of the rescuers were studied in 8 male volunteers.Cardiopulmonary resuscitation for 5 minutes at 3700 m significantly reduced arterial blood oxygen saturation and increased rate-pressure products (P.05). Scores on the Borg scale, a subjective score of fatigue, after CPR action at 2700 m (P.05) and 3700 m (P.01) were higher than the scores at sea level.Prolonged CPR at high altitude exerts a significant physical effect upon the condition of rescuers. A role for mechanical devices should be considered wherever possible.

The number of alpine accidents involving older trekkers has increased markedly in developed countries in recent years. More than 76.8% of the trekkers involved in alpine accidents in Japan were older than 40 years, with some experiencing a stroke or myocardial infarction while trekking at altitude. In the present study, we surveyed social trends in trekkers by interview at a popular mountain site, Mt Tanigawa (1963 m in altitude). The total number of trekkers interviewed was 511, and more than 60% of these were older than 40 years. Of trekkers older than 60 years, 42% complained of conditions such as hypertension or diabetes. In 2 volunteer groups (10 younger subjects and 10 older subjects), physical condition was assessed before and after trekking. Significant body weight loss induced by dehydration was observed more often in older subjects than in younger subjects (P < .05). Balance, as measured using the Nintendo WiiFit (Nintendo, Kyoto, Japan), worsened in the older group (P < .05). Local police records for 2009 showed that the total number of alpine accidents was 65. Injuries provoked by stumbling, slipping, and falling accounted for 51% of these, and 82% of casualties were older than 40 years, with 35% being older than 60 years. In conclusion, many older people involved in nonchallenging middle-altitude trekking have problems with regard to overall health and balance. Alpine accidents caused by myocardial infarction, stroke, or hypoglycemia tend to be more common in this population. Alpine rescue teams should be well prepared for this, and older trekkers should be made aware of their increased risk of injury in alpine settings.

Pseudomyxoma peritonei is a condition characterized by the production of a large amount of mucopolysaccharide by a neoplastic epithelium. Although surgical removal of the mucinous ascites may be attempted, complete removal of the material is difficult. Thus, intra-peritoneal lavage with the liquid containing glucose or dextrose has been advocated to prevent reaccumulation of the mucus and complications such as bowel obstruction requiring repeated surgery. We report a case showing transient hyperglycemia following intra-peritoneal irrigation with 5% glucose in a patient with psudomyxoma peritonei. The patient was a 72-year-old woman. Preoperatively, she had hypertension and angina pectoris; but no history of glucose intolerance. Serum glucose was 92 mg x dl(-1). General anesthesia was induced with propofol (100 mg), vecuronium (6 mg), and fentanyl, and maintained with oxygen (33%), nitrous oxide and sevoflurane (1-2%). A mucinous tumor was found with a great deal of mucinous ascites. To remove the mucus and prevent subsequent re-accumulation, intra-peritoneal irrigation with 5% glucose in water was performed. Shortly after this procedure, the patient was found to be hyperglycemic (serum glucose 266 mg x dl(-1)) with normal oxygenation and hemodynamic data. The patient recovered uneventfully and could be extubated soon after surgery. Serum glucose level returned to 154 mg x dl(-1) one hour after surgery. Therefore, we think that this acute hyperglycemic condition, presumable due to intra-peritoneal irrigation, was transient. It is important to be aware of this dangerous complication associated with intra-peritoneal glucose instillation. Glucose monitoring during and after irrigation with glucose or dextrose is recommended.

A lysophospholipase D (lysoPLD) was purified to apparent homogeneity from rat brain nuclear fractions using 1-[(14)C]palmitoyl-glycerophosphorylcholine as a substrate. The abundance of autotaxin (ATX), a secretory lysoPLD, was also estimated for each fraction. The nuclear fraction had relatively high levels of lysoPLD activity but weak immunoreactivity with an anti-ATX antibody. LysoPLD activity was further purified 5550-fold by sequential chromatography. The final preparation migrated as a single band with a molecular weight of 35,000. Anti-ATX antibodies did not cross-react with the purified enzyme. Moreover, enzyme activity was highest at pH 7.0-7.5 and requires Mg(2+). The Km and Vmax values for 1-palmitoyl-glycerophosphorylcholine were 176 microM and 0.3 micromol/min/mg, respectively. The purified enzyme hydrolyzed saturated forms of LPC more robustly than unsaturated forms. The enzyme could hydrolyze platelet-activating factor (PAF) to the same extent as 16:0-LPC, and showed a higher activity toward lysoPAF (1-O-hexadecyl-2-lyso-glycerophosphorylcholine). These results suggested that the lysoPLD purified from rat brain nuclear fractions in this work is a novel enzyme that hydrolyzes lysoPAF, PAF, and LPC to liberate choline.

The purpose of this study was to assess the effect of gynecologic laparoscopy on propofol concentrations administered by the target-controlled infusion (TCI) system. Thirteen patients undergoing gynecologic laparoscopy (intraabdominal pressure of 10 mmHg) were enrolled in this study. Anesthesia was induced with vecuronium 0.1 mg.kg(-1) and propofol, then maintained by 60% nitrous oxide and sevoflurane in oxygen and a constant infusion of propofol. Propofol was administered to all subjects by means of a target-controlled infusion to achieve propofol plasma concentration at 6.0 microg.ml(-1) at intubation and 2.0 microg.ml(-1) after intubation. Before and during laparoscopy, plasma propofol concentration was determined using high-performance liquid chromatograhy. Cardiac output (CO) and effective liver blood flow (LBF) were also measured using indocyanine green as an indicator. Before and during pneumoperitoneum, there were no significant differences in propofol concentrations between each point. Propofol concentrations were well achieved to predicted concentrations administered by the TCI system during gynecologic laparoscopy under propofol and sevoflurane anesthesia.

A transportable hyperbaric chamber durable for 15 psi of pressure was used to treat a patient suffering from moderate acute mountain sickness at 3700 m above sea level. The symptoms were ameliorated a few minutes after pressurization in the chamber. After a 20-minute stay in the chamber, the patient was completely free of symptoms. Since the chamber can be inflated by using compressed air from a cylinder, no strenuous work was required of the operators. This transportable chamber seems to be useful for the treatment of high-altitude disorders at around 3000 m above sea level.