Joran is set in an alternate historical Japan, the 64th year of the Meiji era (1931 A.D.), where the shogun Tokugawa Yoshinobu continued to reign over Japan instead of handing over power to a Prime Minister. The nation of Japan discovered the "Dragon Vein" (龍脈, Ryumyaku), a unique energy source, within its own borders that allowed Japan to dramatically increase its technological progress through the Edo period. Despite this unexpected prosperity, the government is threatened by an insurgent group known as "Kuchinawa," which hates the isolationist policies of Tokugawa and aims to overthrow the Shogunate.In response, the Tokugawa government has created "Nue," a secret police organization dedicated to rooting out Kuchinawa. Sawa Yukimura is orphaned after her family are murdered by Kuchinawa to obtain a quantity of their blue blood which has the ability to transform humans into "Changelings", demonic beasts associated with animals. She unwillingly becomes an assassin for Nue in the hope of seeking revenge on her family's murderers.
The presence of extracranial fibers arising from meningeal nociceptors, and the demonstration of extracranial pathology in the form of inflammation, may address the question as to why centrally-directed treatment for migraine are so often ineffective. The standard pharmacological treatment for CM or CTTH has traditionally been centrally acting agents that reduce neuronal excitability, such as anti-convulsants and anti-depressants [8]; however, adherence to such treatment regimens is low, indicating low efficacy, at least for some patients [16, 17]. Similarly, behavioral interventions such as Cognitive Behavioral Therapy, while highly effective for some individuals [18, 19], often do not provide adequate and prolonged headache reduction. As a result of inadequate efficacy of these centrally-directed treatments, several treatments directed at the extracranial portion of the head and neck have been increasingly incorporated into the practice of headache medicine over the last decade. Such treatments include occipital nerve blocks [20], trigger point injections [20], botulinum toxin injections [21], and more recently, the use of monoclonal antibodies targeting the calcitonin gene related peptide pathway acting mostly outside of the blood-brain barrier [22].
Blood Red Snow Epub 26
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Hemoglobin is the oxygen-carrying protein contained inred blood cells (erythrocytes). Although normally present in onlytrace amounts, there are three species of hemoglobin that cannottransport oxygen.
Carbon monoxide is produced endogenously but is also a commonenvironmental pollutant; both sources contribute to the amount ofCOHb in blood. The focus of this article is causes and clinicalsignificance of an increased amount of COHb. Three illustrativecase histories will be discussed.
Each of the 5 1010 erythrocytescontained in every mL of blood contains 280 million Hb molecules.The Hb molecule comprises four polypeptide subunits (the globinportion) each of which has a heme group attached [1].
Oxygen has to compete with other hemoglobin-binding ligands thatmay be present in blood for occupation of hemoglobin binding sites;among these is carbon monoxide, a colorless odorless gas producedduring normal metabolism.
Thus endogenously produced carbon monoxide is not, as was oncesupposed, simply a potentially toxic waste product of metabolismbut is involved in many physiological functions, includingregulation of respiration [5], neuronal signaling [6], regulationof blood pressure [7] and uterine contraction during pregnancy[8].
This provides the means by which endogenous carbon monoxide can betransported, prior to elimination from the body by the lungs inexpired air. A minimum of 0.5-1.0 % COHb is inevitably present inblood as a result of endogenously produced CO [9].
The mostsignificant unnatural source of environmental CO is motor-vehicleexhaust. Although normally present at concentrations of less than10 parts per million (ppm) [10], carbon monoxide in inspired airhas an important additive effect on the amount of COHb in blood dueto the high affinity that Hb exhibits for CO.
The amount of COHb in blood is determined principallyby the amount of CO in blood. The source of the CO in blood is bothendogenous (heme catabolism) and environmental (CO content ofinspired air) so that the causes of raised COHb can be addressedunder two main headings:
The toxicity of CO is due in part to the effect thathemoglobin binding of CO has on the oxygen-carrying capacity ofblood. Affinity of hemoglobin for CO is 200-250 times greater thanthat for oxygen [9, 20, 23, 24].
It is now clear that "free" COdissolved in blood plasma enters tissues and competes with oxygenfor sites on tissue-cell heme proteins such as myoglobin,peroxidase and the cytochrome enzymes with a variety ofpathological effects independent of hemoglobin CO binding [20].
However, it also means that if there is more than a few hours delaybetween exposure and sampling of blood, COHb will not accuratelyreflect exposure. In this case, 13 hours elapsed between the timethe boy was found and the time blood was sampled.
Given a half-lifeof 4 hours, this is time enough for COHb to drop from a peak of say40 % to 5 %. Whilst a raised COHb always indicates CO poisoning, anormal COHb is not sufficient to exclude a diagnosis of COpoisoning if there has been delay between exposure and bloodsampling, especially if oxygen therapy has been administered.
The principle cause of raised COHb in this case was increasedendogenous production of carbon monoxide. This was due to theongoing degradation of hemoglobin within the retroperitonealhematoma formed as a result of accumulating blood.
Apart from this reduced level ofconsciousness, physical examination revealed no abnormalities and apresumptive diagnosis of carbon-monoxide poisoning was made. Within15 minutes of starting 100 % oxygen therapy the girl was awake.COHb of blood sampled before therapy was 35 %.
Unequivocal increase inCOHb indicates either a hemolytic process or more commonlycarbon-monoxide poisoning. Increased COHb reduces tissueoxygenation but this is not the only mechanism of CO toxicity.Laboratory measurement of COHb is the only routinely availableblood test for diagnosis of CO poisoning. 2ff7e9595c
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