Condet

Ronald D. Chervin, M.D., MS

• Department of Neurology
• University of Michigan Health System
• Ann Arbor, MI

With so many years invested in the study of O3 diabetes insipidus radiology discount glimepiride 2 mg on line, it is surprising that only now is the nature of species differences with regard to exercise-associated dosimetry being appreciated diabetes youth foundation of indiana glimepiride 4mg free shipping. Animal studies indicate that the acute morphologic responses to O3 can involve epithelial cells along the entire respiratory tract type 2 diabetes definition nhs 1 mg glimepiride with amex. The pattern of injury parallels the dosimetry profile diabetic amyotrophy cheap 3 mg glimepiride mastercard, with the majority of damage occurring in the distal lung. Along the airways, ciliated cells appear to be most sensitive to O3, while Clara cells and mucussecreting cells are the least sensitive. In the alveolar region, type 1 epithelia are very sensitive to O3 relative to type 2 cells, which have an active metabolic machinery. The more resistant type 2 cells serve as the stem cells for the replacement of type 1 cells. Ultrastructural damage to alveolar epithelia can be observed in rats after a few hours at 0. Hence, from animal studies, it would appear that a single exposure to O3 at a relatively low concentration is not likely to cause permanent damage. On a gross level, when a bronchoscope is used to peer into the human bronchus after O3 exposure, the airways appear "sunburned" and, as with mild skin sunburn, recovery is typical. What is uncertain is the impact of repeated "sun-burning" of the airways and lung. Major reactions pathways of O3 with lipids in lung lining fluid and cell membranes. Studies have shown particular sensitivity to O3 -induced inflammation in neonatal rats that decreased with age into adulthood. However, enhanced sensitivity to O3 again appears in older rats as evidenced by interstitial edema that is not seen in younger adult animals. Older rats have lower ascorbate in the lung and this diminishment of antioxidant capacity may be in part responsible. Elderly humans, however, seem less responsive to the lung function impacts of high ambient O3. The reasons for this are unclear, but caution in linking lung function and inflammation in the O3 response is warranted as these events appear separated in time by about 18 hours. The mechanisms by which O3 causes injury have been studied using cellular as well as cell-free systems. The double bonds within these fatty acids have a labile, unpaired electron which is easily attacked by O3 to form ozonides that progress through a less stable zwitterion or trioxolane (depending on the presence of water); these ultimately recombine or decompose to lipohydroperoxides, aldehydes, and hydrogen peroxide. These pathways are thought to initiate propagation of lipid radicals and autooxidation of cell membranes and macromolecules. Evidence of free radical-related damage in vivo includes detection of breath pentane and ethane and tissue measurements of diene conjugates. Damage to the air-blood interface disrupts its barrier function and promotes inflammation. This inflammatory process is generally transient, but it may also interact with neural irritant responses to affect lung function acutely. This latter response may have implications for those with preexistent inflammation or disease. Thus pain reflexes involving C-fiber networks are thought to be important in the reductions in forced expiratory volumes. On the other hand, animal studies show a prominent role for vagal reflexes in altered airway reactivity and bronchconstriction. There is also evidence to implicate vagal reflexes in cardiac as well as thermal regulation, at least in rodents. It is widely thought that hyperreactive airways may be a marker of predisposition to other pollutants such as sulfuric acid or aeroallergens, but such evidence is limited.

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Victims report a bitter diabetes prevention act 2009 glimepiride 4mg cheap, metallic taste from the meat (most often muscle diabetes warning signs type 1 quality glimepiride 3 mg, liver diabetes clinical definition 2mg glimepiride for sale, ovary blood glucose 75 purchase glimepiride 1 mg with mastercard, and digestive tract), followed immediately by nausea, vomiting, and diarrhea. Within several hours, symptoms include myoglobinuria, a burning sensation around the mouth and extremities, muscle spasms, dyspnea, and dysphonia. Cause of death may be the result of mycocardial injury, although it is known in vitro to be a powerful hemolysin. Puffer Fish Poisoning (Tetrodotoxin) Tetrodon or puffer fish poisoning is caused by the improper preparation and consumption of any of about 90 species of puffer fish (fugu, blowfish, globefish, porcupine fish, molas, burrfish, balloonfish, toadfish, etc. Pufferfish are found in subtropical and tropical marine waters in the Atlantic (including off the coast of Florida), Pacific, and Indian Oceans. The toxin (tetrodotoxin) is located in nearly all the tissues, but the ovaries, roe, liver, intestines, and skin are the most toxic. Toxicity is highest during the spawning period, although a species may be toxic in one location but not in another. Tetrodotoxin is associated with the presence of several bacteria on and in fish and shellfish and is an evolutionary advantage providing protection against predators. A total of 21 species can produce tetrodotoxins including Vibros, Pseudomonas, and E. Tetrodotoxin is a neurotoxin and causes paralysis of the central nervous system and peripheral nerves by blocking the movement of all monovalent cations. The toxin is water-soluble and is stable to boiling except in an alkaline solution. Toxicity is manifested as a tingling or prickly sensation of the fingers and toes; malaise; dizziness; pallor; numbness of the lips, tongue, and extremities; ataxia; nausea, vomiting, and diarrhea; epigastric pain; dryness of the skin; subcutaneous hemorrhage and desquamation; respiratory distress; muscular twitching, tremor, incoordination, and muscular paralysis; and intense cyanosis. Moray Eel Poisoning Although the moray eel (Gymnothorax javanicus) and other carnivorous fishes may accumulate ciguatoxin as the result of eating other contaminated fish, the Indo-Pacific moray eel (Lycodontis nudivomer) has been shown to possess a mucous skin secretion with hemolytic, toxic and hemagglutinating properties, unrelated to ciguatoxin. The hemolytic property is lost upon treatment with trypsin and is unstable in the presence of heat, acidic or alkaline media (Randall et al. The skin mucous of other species of eels, the common European eel (Anguilla anguilla) and pike eel (Muraenesox cinereus) were found to have proteinaceous toxins, immunologically similar to that of the skin mucous toxin from the Japanese eel (Anguilla japonica) (Shiomi et al. Abalone Poisoning (Pyropheophorbide) Abalone poisoning is caused by abalone viscera poison (located in the liver and digestive gland) and is unusual in that it causes photosensitization. The symptoms are of sudden onset and include a burning and stinging sensation over the entire body, a prickling sensation, itching, erythema, edema, and skin ulceration on parts of the body exposed to sunlight (Bryan, 1984; Shiomi, 1999). Sea Urchin Poisoning the etiologic agent forms during the reproductive season and is confined to the gonads. The sea urchins involved include Paracentrotus lividus, Tripneustes ventricosus, and Centrechinus antillarum. The symptoms include abdominal pain, nausea, vomiting, diarrhea, and migraine-like attacks (Bryan, 1984). The toxin has been shown to interfere with calcium uptake in nerve preparations (Zhang et al. Sea Turtle Poisoning (Chelonitoxin) the etiologic agent here is chelonitoxin, which is found in the liver (greatest concentration) but also in the flesh, fat, viscera, and blood. Toxicity is described as sporadic or even seasonal, indicating the poison may be derived from toxic marine algae. The turtles involved include the green sea turtle, the hawksbill and leatherback turtles. Local custom in Sri Lanka is to first offer the liver to crows and if the birds eat it, the flesh is regarded as safe, but because the symptoms appear over a few hours to several days, this bioassay requires patience. Symptoms of intoxication in humans include vomiting; diarrhea; sore lips, tongue, and throat; foul breath, difficulty in swallowing; a white coating on the tongue, which may become covered with pin-sized, pustular papules; tightness of the chest; coma; and death. The toxin has been reported transferred to nursing infants from intoxicated mothers. Post-mortem examinations reveal congestion of internal organs, interstitial pulmonary edema, and necrosis of myocardial fibers.

Although the animal and human toxicological database is growing rapidly with regard to the issue of causation diabetes diet patient education purchase glimepiride 1 mg with amex, much remains to be learned before new regulatory indices can be considered metabolic disease questions glimepiride 2 mg on-line. Organic constituents diabetes type 2 autoimmune order 1 mg glimepiride otc, as well diabete insipidus buy glimepiride 4mg amex, can induce toxicity either directly or via metabolism product-some of which are genotoxic. Studies focusing on very small, ultrafine particles suggest that although these particles are low in mass, they are high in number and thus provide substantial reactive particle surface to interact with biological substances. Less is known about the role of biologically derived materials, such as endotoxin, other plant glycoproteins, and bioallergen fragments, which may elicit rudimentary inflammatory responses in the lung. The involvement of biologicals may be greatest in agricultural and indoor exposure environments. In this regard, toxicologists need to better access the experience and knowledge of atmospheric scientists as to atmospheric interactions that are most relevant to biologic outcomes. Metals There have been many standard acute and subchronic rodent inhalation studies with specific metal compounds, often as oxides, chlorides, or sulfates. The varied systemic toxicities of metal compounds are presented in detail elsewhere in this text; however, it should be appreciated, that the effects of metals delivered by inhalation may differ from their impacts when administered by other routes. For example, oil may have vanadium, nickel, and perhaps zinc and iron, whereas coal may have zinc and selenium. Other metals are emitted from vehicles burning fuels to which metal compounds were added to alter functionally (e. Similarly, metals may also derive from brake (copper, iron), tire (zinc) and dispersed road (earthen silicates) wear. As metals have many biologic properties, some essential to life while others being directly toxic to cells or act indirectly in a pro-oxidant toxic fashion. Metal compounds can be separated nominally by physicochemical characteristics: those that are essentially water-insoluble (e. Solubility appears to play a role in the toxicity of many inhaled metals by enhancing metal bioavailability (e. Moreover, some metals, either in their soluble forms or when partially coordinated on the surface of silicate or bioorganic materials, can promote electron transfer to form reactive oxidants (Ghio et al. Complexes with particulate organic material in a partially hydrated form (as might be promoted by the presence of sea salt) have been shown to interact with poorly soluble metals to free coordination sites that again are pro-oxidant (Kieber et al. Simply measuring total metal mass to estimate effects in the lung can be misleading. Gas-Particle Interactions As already noted, these interactions can be extremely complex involving multiple components of the particles, gases/vapors, and sunlight. However, more than 30 years ago, generic binary interactions between particles and gases in the absence of light was shown to alter the toxicity of either the particle or the gas acting alone. The metal salts of manganese, iron, and vanadium, on the other hand, catalyzed the formation of sulfate (Amdur and Underhill, 1968). The degree of response to the mixture was dictated by the aerosol concentration, indicating that it was the proximate irritant. Studies in humans have been less revealing about such interactions, but this database affirms the need to consider the complexity of the atmospheric challenge in estimating biological outcomes. Using a laboratory scaled furnace, the emission mix of sulfuric acid and metal oxide particles common to metal smelting and coal combustion was used to explore potential plume interactions that might impact respiratory irritancy (Amdur et al. These emitted metal oxide particles, once aged and cooled, were a mixture of singlet and agglomerated ultrafine particles that would be expected to distribute throughout the lung upon inhalation. It is unclear whether the acid was on the surface of the particles or dissolved the particles, but the combination was clearly more toxic than acid alone. Combustion studies using different coals again emphasized the significance of surface associated acidic S-compounds. Despite the greater sulfur content of this coal, this emission ultrafine particle had adsorbed the less irritating neutralized sulfate (Chen et al. Similar studies using inert carbon black appear consistent with its role as carrier for reactive gases such as O3 and various aldehydes to enhance delivery of toxic materials to the deep lung (Jakab, 1992). The result of the latter study was enhanced infectivity when the test animals were subsequently exposed to pathologic bacteria. Similar interactions may result from gaseous pollutants that impair the clearance of particles from the lung or otherwise alter their metabolism. It was thought that impaired clearance and greater residence time in the lung led to the enhanced the probability of carcinogenic expression of the particle. Similarly, rats exposed to an urban 8-hour daily profile of O3 for 6 weeks, followed by a 5 hour exposure to asbestos, were found to retain three times as many fibers as did the controls 30 days postexposure.

Diseases

• Usher syndrome, type IB
• Continuous spike-wave during slow sleep syndrome
• Glucocorticoid sensitive hypertension
• Mixed connective tissue disease
• Popliteal pterygium syndrome
• Dental fluorosis
• Raine syndrome
• Extrasystoles short stature hyperpigmentation microcephaly
• Infantile digital fibromatosis
• Marles Greenberg Persaud syndrome

For example blood glucose random cheap glimepiride 3 mg with visa, far from being a James Bond villain with a powerful underground fortress and a vast secret army funded by his millions diabetes signs n symptoms buy discount glimepiride 3mg line, `Usama is quite marginal diabetes wiki discount glimepiride 2mg visa, financially (Myth #2; Pages 23-32) diabetes in dogs and skin conditions discount glimepiride 2mg overnight delivery. I bought a box of Cheez-Its recently, clearly wrote "Osama" on the front, and put it on the top shelf. This was debunked often enough, but it goes with the others (Myth #6; Pages 57-64). Ipse dixit: "Myth #11: There is no evidence that Iraq had weapons of mass destruction" except the ones that they had (Pages 97-106). Miniter gives a list of the various minor but by no means insignificant stocks of poison gas and other deleterious substances that were found in Iraq. One would think that an analysis of the well-off, even wealthy backgrounds of the nihilist New Leftists of the Red Brigades, Weathermen, and the like would have disproved this (cf. But the hijackers were all well educated men from well-to-do families, just as the murdering bombers of today are from well-to-do families. W hile "suitcase nukes" are the McGuffin of many thrillers, the definition of "suitcase" is very broad. This unfortunate but necessary debunking even ruins the line "Just find the camel with the dialysis machine, and follow it. When you were young, you knew that the stuff inside golf balls was poisonous, learning it from the most reliable of sources; some kid who knew someone who had heard of someone whose brother had seen it happen to a friend. The result, though, is all too often no more reliable than "a friend of a friend had a cousin who saw someone. More seriously (though the whole development is as absurd as a M arx Brothers movie - the Paramount ones, the earlier ones) the statistics of the "missing suitcase nukes" change according to who the source is or even when he is talking. Miniter quotes Alexander Lebed giving contrad ic to ry figures a nd o therwise demonstrating a desire for sensationalism over information. On the one hand, he exposes the depths of the relationship of Halliburton with the government, detailing their fiendish plot to make Halliburton lose money big time (Myth #20; Pages 159-166) and on a cost-plus contract at that. On the other, he discusses why, for all that it is disarrayed and overrun by narcotraficantes, possessed of one of the leakiest border in history, Mexico is not the most likely place from which hostile foreigners may infiltrate the Great Satan; there is a far more hospitable (both intellectually and organizationally) location elsewhere (Myth 22; Pages 177-188). As a polemic, this fails, but through no fault of Miniter (or his indefatigable researcher); the book contains welldocumented (often excruciatingly so) evidence backing up its refutations. But Miniter here is arguing against conspiracy thought; nothing he or anyone else says is going to convince the fanatic, the one who believes beyond a shadow of a doubt that these refutations are fraud, and that a shallow but satisfying cartoon by Tom Tomorrow is a more than adequate refutation of them. Next you make sure that the animals have indeed eaten all the food from the previous feeding. At this point, the cats will start circling you, requiring you to go slowly so as not to be tripped up. When you arrive in the kitchen all the felines will mob you in a desperate attempt to frustrate you from your purpose of getting food neatly into the bowls. I remember telling them once that we could feed them every hour on the hour and they would still act like little animals. Saturday was full of activity: breakfast at the hotel restaurant, then hanging out in the con suite. We were told to act like chickens - fans seem to be a shy bunch sometimes, we clucked and did the "chicken dance". Menu items have theme oriented names - an Page 18 December 2005 Alexiad ice cream dish for example is called a "James Bomb" and looks like a cartoon bomb including a candle-fuse. After lunch and exploration we rounded up the troops and headed to Sprecher for a Brewery tour. Sprecher is a microbrewery and I was surprised to find that they shipped all over the U. They are well loved by me because they use honey as a sweetener rather than sugar or High Fructose Corn Syrup. At the end of the tour they had a product testing (limit of four beers in a fourounce glass and endless soda) served in souvenir glass. Custard is kind of like ice cream but better, one of the differences is that frozen custard employs eggs. The show might have a flavor that has been crafted to strike something in the audience that relates to present current events. This requires the audience to further utilize their imagination and their creative abilities. You witness a specialized form of theatre and artistry: the story is being portrayed from beginning to end - the actor living this full arc of life in sequence over a period of perhaps two hours.

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