Verizon to Disconnect Unlimited Data Users Who Use "Extraordinary" Amounts of Data. Hey buddy, you, the one who is consuming massive amounts of 4. G LTE data on your Verizon unlimited data plan and is out of contract. You will want to pay attention to what I’m about to share. Come August 3. 1, if Verizon deems your account as using “an extraordinary amount of data” each month, you could see your line completely disconnected. In other words, Verizon may shut you down by the end of August. According to sources of ours, Verizon is working on an Unlimited Data Plan Migration for the highest unlimited data users on their network. Download Games Torrents for PC, XBOX 360, XBOX ONE, PS2, PS3, PS4, PSP, PS Vita, Linux, Macintosh, Nintendo Wii, Nintendo Wii U, Nintendo 3DS. For free! It’s my nephew’s “netbook”, it’s basically a laptop that runs the Android Kitkat OS. you turn it on and it goes through it’s boot process and after that. After a long time of some mere bugfixes, following by a long time of slow work on the promised refresh Transdroid 2.5 is finally here! The obvious change in the. Should you get the beefy new iPhone 8 Plus? Should you spring for 256GB of storage? Should you finally switch to T-Mobile and its litany of appealing offers? Donald Trump loves a good deal. And the United States Air Force just found one for the president, sitting in a Mojave Desert boneyard: two brand new Boeing 747-8's. Welcome to TECH DroidLife. We provide you the best Android, Windows PC, Kodi, VPN and Technology Tutorials. You can also find the latest tech news and opinions.
Starting tomorrow, July 2. Verizon will begin notifying users who have been flagged as using that “extraordinary” amount via mailer and through bill messages and explain to them their options to stay with Big Red. What are their options? Verizon is forcing these out of contract “extraordinary” data users to move to The Verizon Plan (a tiered plan) by August 3. If they don’t take that option by August 3. The Verizon Plan. As of right now, we do not know what an “extraordinary” amount of data is. Are we talking 2. GB per month? 5. 0GB? GB? We’ll be sure to let you know if we find out. Verizon has confirmed to us that they will begin notifying a “small group” of customers (via both bill message and letter) who use that “extraordinary” amount of data, telling them that they will need a new plan by August 3. EDIT: Verizon also told us the following as it relates to “extraordinary” use. Note the 1. 00. GB plan as an example, so take that as you will. These users are using data amounts well in excess of our largest plan size (1. GB). While the 1. GB plan is designed to be shared across multiple users, each line receiving notification to move to the new Verizon Plan is using well in excess of that on a single device.
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Misc. Unsigned Bands - Chordie. Vinyl records, LPs, 12s, 45s and CDs NOW in stock at www.Vinylsearch.com. AGNETA FALSTKOG. A-HA. Birthright Cast In Steel (jb) Cry Wolf Crying in the rain Dark Is The Night For All. Taxi Driver – Plano Crítico. Spoilers. 19. 76 foi um dos anos mais ilustres da Nova Hollywood, movimento que fez os filmes mais corajosos e brilhantes durante os anos 1. Um dos filmes mais aguardados do ano, It: A Coisa chega com a expectativa de se tornar um novo clássico do terror. Entretanto, o bom momento não centrava apenas em Hollywood. O mundo estava empenhado em entregar ótimas obras. Para ver como esse ano foi tão sublime, estreias de longas imortais como Rocky, Rede de Intrigas, Todos os Homens do Presidente, Maratona da Morte, O Inquilino, O Império dos Sentidos, Feios, Sujos e Malvados, A Profecia e Carrie, A Estranha. Porém, acredito, que poucos desses excelentes filmes se aproximem do tamanho do fenômeno que se tornou Taxi Driver.
Nas noites frias e escuras de Nova Iorque, um taxista circula pelas entranhas da cidade. A melancolia o persegue acompanhada da repulsa que sente por todos à sua volta. Completamente sem perspectiva, Travis Bickle pretende assassinar um político a fim de mudar sua vida. Porém, um encontro inesperado com uma jovem prostituta muda seu destino amaldiçoado. Para entender Taxi Driver como um todo, é preciso entender a vida pessoal naquele momento de Martin Scorsese e do roteirista Paul Schrader. Não é por mera conveniência narrativa que os dois criaram um dos melhores personagens de toda a cinematografia mundial. Há muito de Schrader e Scorsese – até mesmo de De Niro, no solitário Travis Bickle. A relação de Taxi Driver com Scorsese é antiga. Paranaense, 26 anos, casada. Administradora por profissão, blogueira por paixão. Doida por livros, filmes e series de TV.Ele implorava para dirigir o filme desde 1. Porém, a sina de Scorsese é forte. Com a recepção calorosa de Caminhos Perigosos e Alice Não Mora Mais Aqui, os produtores finalmente cederam pela pressão de Scorsese em dirigir o filme. Em 1. 97. 4, enfim, um dos melhores filmes de todos os tempos, começava a ser produzido. Durante a concepção do roteiro, Schrader pegou muito do seu íntimo e colocou no papel. Toda a melancolia, a fixação por armas, a tentativa de suicídio, a depressão, as noites passadas em claro por remédios, a alienação de Travis vem da vida conturbada de Schrader. Não é por menos que Scorsese tenha se identificado tanto com a desventura de Travis também. Em Los Angeles, Scorsese sentia- se sozinho, passava por um período muito complicado envolvido demais com cocaína e bebedeira. Estava se perdendo no típico descontrole pessoal, financeiro e psicológico que abocanhou muitos realizadores nessa época de ouro hollywoodiana – para se ter uma ideia, apenas De Palma, Spielberg e Lucas não caíram na armadilha das drogas e da fama. Esse período sombrio da vida de Scorsese só se encerraria após a conclusão de Touro Indomável quando quase morreu de overdose. Nessa união tão intensa e apaixonada por se verem retratados na depressão de Travis, também entra De Niro. Mesmo com segredos melhores guardados, algo afetou De Niro. Ele cobrou um cachê ínfimo logo após ter recebido seu merecido Oscar em O Poderoso Chefão 2. Sua boa vontade com o projeto foi recompensada quando Scorsese tomou Touro Indomável para dirigir – era um roteiro que De Niro insistia com todas as suas forças para que o diretor pegasse para si desde 1. O roteiro de Schrader, talvez por ser tão pessoal, é algo impecável. Um dos acertos mais genuínos que podemos ter o privilégio de assistir. Entenda, eu não tenho absolutamente nenhuma ressalva com Taxi Driver por mais chato e criterioso que eu seja. História do Cinema. Não só a história que tem inspiração no assassinato dos Kennedy nos anos 1. Travis Bickle mesmo sendo um personagem contido sempre centrado em apenas um conflito: como ser relevante mesmo sendo um loser alienado? A magia de Taxi Driver vem muito do nosso desconhecimento sobre diversas coisas. Nós nunca sabemos o passado de Travis, mesmo que praticamente o filme inteiro seja contado através de seu ponto de vista, mas há a suspeita dele ser veterano da Guerra do Vietnã – principalmente por conta do moicano que ele adota no fim do longa. Pela própria natureza calada do protagonista, o pouco que sabemos vem através da narração over justificada pelo diário no qual ele aparentemente escreve em algumas passagens. Através dele e, também da direção impecável de Scorsese, descobrimos que o personagem é racista, tem ódio a prostitutas, além do desejo assassino em “limpar” as ruas de Nova Iorque. Enfim, a disseminação da mente doentia de Travis é realizada com competência. Exterminar a todos que ele julga inaptos a viver em sociedade. Porém, com muita esperteza, Schrader não transforma Travis em um estúpido superficial que tem ódio do mundo. No cerne de dois conflitos, o protagonista passa a ter um vislumbre, um desejo de uma vida melhor. Ele sente vontade em mudar os rumos decadentes de seu cotidiano. Isso se dá quando ele se apaixona por uma gerente de campanha do político Palentine, Betsy. Para entender como o romance é completamente flácido desde o primeiro contato direto de Travis com Betsy, é preciso notar o grande trabalho de Scorsese na direção. Repare que na cena que ocorre no encontro da cafeteria, Scorsese, quando toma o ponto de vista de Travis, sempre enquadra o campo que observa Betsy com o ombro de Travis emoldurando o enquadramento. Já quando tomamos o ponto de vista de Betsy para definir o contracampo da cena – este, observando Travis – ela nunca está incluída na moldura como referência. Isso indica como, na verdade, nunca os personagens possuem alguma ligação romântica sequer contradizendo completamente o discurso truncado de Travis em inferir uma conexão amorosa forte com a personagem.É uma ironia fantástica que já indica o quão cínico o filme se tornará em sua conclusão. O texto de Schrader, para definir o diálogo, é inteligente em sempre fazer Travis puxar vários assuntos, small talk, a fim de estabelecer a tentativa da conquista amorosa. Nesse primeiro instante, é muito lógico que aquele romance está fadado ao fracasso. Pior, a técnica de Scorsese é tão cruel com Travis que desiste do plano conjunto que unia os dois assim que o protagonista faz uma piada ruim para Betsy, mas o retoma para concluir a cena quando ela aceita sair para um segundo encontro onde novamente Schrader explicita uma característica definidora de Travis: a sua alienação. Nesse ínterim entre um encontro e o outro, Schrader introduz pela primeira vez outra personagem fantástica inspirada em uma jovem prostituta que ele conheceu: Iris. A relação da menina com Travis foge completamente do convencional, pois sua presença no longa é intermitente: ela some e aparece justamente quando pensamos o que teria ocorrido com ela. Em todas as vezes que assisto Taxi Driver, isso acontece. Me pergunto onde está Iris para então ela surgir em suas primeiras cenas envolvidas em mistério. O roteirista sabe precisamente onde inserir os momentos corretos para retomar o arco de Iris. Como ficamos sempre centrados com Travis, os retornos com Iris são brevíssimos. Nas sequências destinas à apresentação do cotidiano e rotina de Travis, acertadamente Schrader não se preocupa em traçar histórias marcantes de passageiros, afinal essa nunca foi a proposta do filme. Na verdade, mais vemos Travis isolado em seu táxi durante as horas de trabalho. Porém, um encontro é vital para transformar o personagem de depressivo em psicopata. Com o homem misterioso ansioso em matar sua mulher infiel – interpretado muitíssimo bem por Martin Scorsese por falta de opção – Schrader trabalha pela primeira vez com a descontinuação de um arco, além de reapresentar a subjetividade. No discurso do Homem, ele cita a Magnum 4. Para Travis, o modelo da arma permanece em sua mente, além de teor assassino da conversa. Não interessa ao protagonista se ele matou a mulher ou não. Só a violência permanece. Algo que é recorrente no texto de Schrader é a solidão auto imposta do protagonista. Em diversos momentos- chave do longa, vemos ele flertando com a ideia de ter alguma companhia romântica – tudo muito sutilmente inserido em sequências noturnas que focam, em slow motion, alguns casais e mulheres. Fora isso, há diversos encontros com outros taxistas que sempre tentam incluir Travis no papo. Nada é inferido no texto, mas pela câmera e da atuação monstruosa de De Niro, é possível detonar que o personagem acredita que não merece nenhum tipo de carinho. Ele se sente deslocado de todo o ambiente. O segundo encontro de Travis com Betsy ao levá- la para ver um filme pornográfico explicita de vez sua alienação e isolamento imposto por si próprio. A partir daí, por conta desilusão amorosa, Schrader passa a investir no “plano” de Travis em assassinar Palantine. Nessa sequências, vemos diversos rituais do protagonista. Seja nos treinamentos com as armas, na criação de engenhocas que revelam um talento esquecido do personagem e sessões de condicionamento físico – todas acompanhadas de narração over. Nessas sequências há peças que tornam cinema em Cinema. Por exemplo, quando Travis aparentemente escreve uma carta para seus pais dizendo que está vivendo bem e vendo oportunidades boas para o futuro. Durante o discurso, somente imagens de Palantine aparecem em tela. A ideia fixa do assassinato persegue sua menta insana. As contradições marcam sempre esses discursos do diário apresentados nos rituais. Travis diz que precisa ficar saudável, mas se entope de remédios para ficar acordado, além de sua mente já estar comprometida. Ele flerta com sua autodestruição. No ápice de sua loucura, Travis conversa consigo mesmo no espelho. Trata- se, claro, da cena antológica que Robert De Niro improvisou em um dos ensaios. You talkin to me? No texto de Schrader, estava escrito apenas “Travis se encara no espelho e conversa sozinho”. Os olhares psicóticos e de fascinação de De Niro em sua performance assombrosa, revelam a sua relação amorosa platônica com as armas de fogo. A elaboração textual de Taxi Driver é tão intrínseca à direção que julgo impossível separá- las uma da outra. Scorsese faz o texto de Schrader crescer assustadoramente com seus lances muito espertos de mise en scene que toma emprestado referências que cercam o cinema noir de 1. 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The high- water mark of the battle was the massive armor engagement at Prochorovka (also spelled Prokhorovka), which began on July 1. But while historians have categorized Prochorovka as a victory of improved Soviet tactics over German firepower and heavy tanks, new evidence casts the struggle at the ‘gully of death’ in a very different light. Play free online flash Xiangqi II: Xiangqi(Chinese chess) is the most popular board game game. Free download computer games. Download the best puzzle, sim, hidden object and mahjong games. Free download modern remakes of old school retro games. The Germans’ goal during Citadel was to pinch off a large salient in the Eastern Front that extended 7. Field Marshal Günther von Kluge’s Army Group Center would attack from the north flank of the bulge, with Colonel General Walther Model’s Ninth Army leading the effort, General Hans Zorn’s XLVI Panzer Corps on the right flank and Maj. Gen. Josef Harpe’s XLI Panzer Corps on the left. General Joachim Lemelsen’s XLVII Panzer Corps planned to drive toward Kursk and meet up with Field Marshal Erich von Manstein’s Army Group South, Col. Gen. Hermann Hoth’s Fourth Panzer Army and the Kempf Army, commanded by General Werner Kempf.
Opposing the German forces were the Soviet Central Front, led by General Konstantin K. Rokossovsky, and the Voronezh Front, led by General Nikolai F. Vatutin. The Central Front, with the right wing strengthened by Lt. Gen. Nikolai P. Pukhov’s Thirteenth Army and Lt. Gen. I. V. Galinin’s Seventeenth Army, was to defend the northern sector. To the south, the Voronezh Front faced the German Army Group South with three armies and two in reserve. The Sixth Guards Army, led by Lt. Gen. Mikhail N. Chistyakov, and the Seventh Guards Army, led by Lt. Gen. M. S. Shumilov, held the center and left wing. East of Kursk, Col. Gen. Ivan S. Konev’s Steppe Military District (renamed Steppe Front on July 1. German breakthroughs, then mount the counteroffensive. If their plan succeeded, the Germans would encircle and destroy more than five Soviet armies. Such a victory would have forced the Soviets to delay their operations and might have allowed the Wehrmacht desperately needed breathing room on the Eastern Front. Model’s Ninth Army never came close to breaking the Soviet defenses in the north, however, and soon became deadlocked in a war of attrition that it could not win. On the southern flank, Kempf’s III Panzer Corps, commanded by General. Hermann Breith, also encountered tough Soviet resistance. By July 1. 1, however, Hoth’s Fourth Panzer Army was in position to capture the town of Prochorovka, secure a bridgehead over the Psel River and advance on Oboyan. The Psel was the last natural barrier between Manstein’s panzers and Kursk. The Fourth Panzer Army’s attack on the town was led by SS General Paul Hausser’s II SS Panzer Corps, General. Otto von Knobelsdorff’s XLVIII Panzer Corps and General Ott’s LII Army Corps. Hausser’s corps was made up of three panzer divisions–the 1st Leibstandarte. Adolf Hitler (Adolf Hitler’s bodyguard), 2nd SS Das Reich (The Empire) and 3rd SS Totenkopf (Death’s Head). Although all three were technically Panzergrenadier divisions, each had more than 1. Citadel began. Knobelsdorff’s corps was composed of the 1. Panzergrenadier Division Grossdeutschland and Panther Brigade Decker, and Ott’s corps contained the 2. Opposing Hausser at Prochorovka was the newly arrived and reinforced Fifth Guards Tank Army, commanded by Lt. Gen. Pavel A. Rotmistrov. The Fifth Guards was the Soviet strategic armored reserve in the south, the last significant uncommitted armored formation in the sector, with more than 6. The Soviet operational armored reserve, General Mikhail E. Katukov’s First Tank Army, was already in action against Hoth’s Fourth Panzer Army south of the Psel. Katukov’s army had been unable to prevent the Germans from reaching the river, however. His VI Tank Corps, originally equipped with more than 2. July 1. 0 and 1. 1, and the other two corps of Katukov’s army also had sustained serious losses. On July 1. 0, the 3rd SS Division Totenkopf, commanded by SS Maj. Gen. Hermann Priess, had established a bridgehead over the Psel, west of Prochorovka. By July 1. 1, the division’s panzer group had crossed the river on pontoon bridges and reached the bridgehead. What was left of Katukov’s armor regrouped to oppose the XLVIII Panzer Corps below Oboyan or counterattack the Psel bridgehead. Reinforced with the XXXIII Rifle Corps and X Tank Corps, Katukov launched continuous attacks on the Totenkopf units on the north bank of the river. During the evening of July 1. Hausser readied his divisions for an assault on Prochorovka. Totenkopf anchored the left flank of the corps, while Leibstandarte, commanded by SS Maj. Gen. Theodore Wisch, was in the center, assembled west of the town between a rail line and the Psel. Das Reich, commanded by SS Lt. Gen. Walter Krüger, moved into its attack zone on the corps’ right flank, which was several kilometers south of Tetrevino and southwest of Prochorovka. While Hausser’s SS divisions prepared for battle, there was feverish activity in the Soviet camp as well. On July 1. 1, the Fifth Guards Tank Army arrived in the Prochorovka area, having begun its march on July 7 from assembly areas nearly 2. The army consisted of the XVIII and XXIX Tank Corps and the V Guards Mechanized Corps. Rotmistrov’s 6. 50 tanks were reinforced by the II Tank Corps and II Guards Tank Corps, increasing its strength to about 8. T- 3. 4s. The Fifth Guards’ primary mission was to lead the main post- Kursk counteroffensive, known as Operation Rumyantsev, and its secondary mission was as defensive insurance in the south. The commitment of Rotmistrov’s army at such an early date is stark evidence of Soviet concern about the situation on the Psel. The Fifth Guards’ arrival at the Psel set the stage for the Battle of Prochorovka. Prochorovka is one of the best- known of the many battles on the Eastern Front during World War II. It has been covered in articles, books and televised historical documentaries, but these accounts vary in accuracy; some are merely incomplete, while others border on fiction. In the generally accepted version of the battle, the three SS divisions attacked Prochorovka shoulder to shoulder, jammed into the terrain between the Psel and the railroad. A total of 5. 00 to 7. German tanks, including dozens of Panzerkampfwagen Mark V Panther medium tanks with 7. Panzerkampfwagen Mark VI Tiger heavy tanks with deadly 8. Soviet T- 3. 4 medium tanks raced into the midst of the SS armor and threw the Germans into confusion. The Soviets closed with the panzers, negating the Tigers’ 8. German armor and knocked out hundreds of German tanks. The Soviet tank force’s audacious tactics resulted in a disastrous defeat for the Germans, and the disorganized SS divisions withdrew, leaving 4. Tigers and many Panthers. Those losses smashed the SS divisions’ fighting power, and as a result Hoth’s Fourth Panzer Army had no chance to achieve even a partial victory in the south. While it makes a dramatic story, nearly all of this battle scenario is essentially myth. Careful study of the daily tank strength reports and combat records of II SS Panzer Corps–available on microfilm at the National Archives in Washington, D. C.–provides information that forces a historical reappraisal of the battle. These records show, first of all, that Hausser’s corps began with far fewer tanks than previously believed and, more important, that they suffered only moderate losses on July 1. As those reports were intended to allow the corps commander to assess the combat strength of his divisions, they can be considered reasonably accurate. Considering that information, it seems that the Germans may have been near a limited success on the southern flank of the salient. The number of SS tanks actually involved in the battle has been variously reported as high as 7. Even before the Battle of Kursk began, however, the II SS Panzer Corps never had 5. On July 4, the day before Operation Citadel was launched, Hausser’s three divisions possessed a total of 3. By July 1. 1, the II SS Panzer Corps had a total of 2. Totenkopf had 9. 4 tanks, Leibstandarte had only 5. Das Reich possessed just 6. Damaged tanks or tanks undergoing repairs are not listed. Only 1. 5 Tiger tanks were still in action at Prochorovka, and there were no SS Panthers available. The battalions that were equipped with Panthers were still training in Germany in July 1. On July 1. 3, the day after the Battle of Prochorovka, Fourth Panzer Army reports declared that the II SS Panzer Corps had 1. Actual losses were somewhat heavier, the discrepancy due to the gain of repaired tanks returned to action. Closer study of the losses of each type of tank reveals that the corps lost about 7. July 1. 2. In contrast, Soviet tank losses, long assumed to be moderate, were actually catastrophic. In 1. 98. 4, a history of the Fifth Guards Tank Army written by Rotmistrov himself revealed that on July 1. He gave no figure for tanks that were destroyed or not available for salvage. Evidence suggests that there were hundreds of additional Soviet tanks lost. Several German accounts mention that Hausser had to use chalk to mark and count the huge jumble of 9. Soviet tanks in the Leibstandarte sector alone. Other Soviet sources say the tank strength of the army on July 1. Those losses brought a caustic rebuke from Josef Stalin. Subsequently, the depleted Fifth Guards Tank Army did not resume offensive action, and Rotmistrov ordered his remaining tanks to dig in among the infantry positions west of the town. Another misconception about the battle is the image of all three SS divisions attacking shoulder to shoulder through the narrow lane between the Psel and the rail line west of Prochorovka. Only Leibstandarte was aligned directly west of the town, and it was the only division to attack the town itself. Free Download Games. Mini Games Downloads. Ouvir Músicas gospel Evangélicas cristã, Musicas em Mp. Online e Videos Evangelicos para baixar e MP3 Gospel, onde você pode não só ouvir musicas gospel como também baixar músicas. Faca parte da nossa equipe. Se voce tem conhecimento aprofundado em Javascript, PHP, mysql e . NET? Entre em contato pelo nosso e- mail. Estaremos abertos a pessoas que queiram crescer juntamente conosco. 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Learn about symptoms, causes and treatment of heart disease, a term describing a wide range of conditions that can affect the heart. This chapter was designed to provide the reader with a brief overview of the current surgical treatment options for heart valve disease. Major topics of discussion. Heart Failure: Management and Prevention of Heart Failure Based on Current Understanding of Pathophysiological Mechanisms. Coronary artery disease (CAD), also known as ischemic heart disease (IHD), is a group of diseases that includes: stable angina, unstable angina, myocardial infarction. Original Article. Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes. Christopher P. Cannon, M.D., Eugene Braunwald, M.D., Carolyn H.Cholesterol Sulfate Deficiency and Coronary Heart Disease. Read the Flipbook and PDF Versions. Every article in the Journal, presented in PDF and Flip. Book, that you can save and read on any device, online and off, anytime. Get Both for $2. ARTICLE SUMMARY• Impaired sulfate supply to the heart is a key factor in cardiovascular disease.• Red blood cells, platelets and cells in the skin synthesize cholesterol sulfate catalyzed by sunlight.• Cholesterol sulfate, unlike cholesterol, is water soluble, so it can travel freely in the blood rather than packaged up inside an LDL particle.• Glyphosate, the active ingredient in the pervasive herbicide Roundup, disrupts sulfate synthesis in the skin and disrupts bile flow from the liver, leading to a systemic deficiency in cholesterol sulfate.• Sulfate provides negative charge in the blood vessel wall and for the red blood cells and platelets, promoting flow.• Sulfate also maintains the structured water that lines the vessel walls and presents a slick, frictionless surface to the red blood cells.• The atheroma actively recruits cholesterol to be ready to produce cholesterol sulfate when sulfate becomes available.• Inflammation, while damaging to surrounding tissues, performs a useful service by promoting an oxidative environment necessary to make sulfate.• A heart attack is a well- choreographed sequence of events aimed to restore sulfate supplies by oxidizing taurine, which is stored in large amounts in the heart.• Statin drugs, by reducing the supply of cholesterol sulfate to the heart, will lead to heart failure down the road, a worse prognosis than cardiovascular disease. Despite decades of research, atherosclerosis remains a poorly explained phenomenon. The simple story experts present to the public is that excess cholesterol accumulates in the blood and combines with other substances to form an atheroma (also called plaque) that lodges in the artery wall, eventually obstructing flow. Strikingly, however, the lipid deposits accumulate only in arteries and never in veins. Even more striking is the fact that the arteries supplying the heart are the most vulnerable. The conventional explanation leaves unanswered many questions about the pathogenesis of atherosclerosis and cardiovascular disease. Why does cardiovascular plaque accumulate only in arteries, and preferentially in arteries supplying the heart? What prompts the occurrence of inflammation, which many believe to be a critical factor in heart disease? Why have studies on vitamin D supplementation proved disappointing despite research showing a strong inverse relationship between sunlight availability and heart disease? To answer these questions, I propose a unifying theory for the etiology of cardiovascular disease. The theory involves cholesterol sulfate, a molecule that circulates in the bloodstream and performs a variety of important regulatory functions. I believe that the cause of heart disease is an inadequate supply of cholesterol sulfate to the heart. When there are pathologies that impair the normal conditions for making cholesterol sulfate, an atheroma develops as an alternative means of supplying the heart with vital cholesterol sulfate. When neither the normal nor back- up mechanisms are able to make adequate cholesterol sulfate, the outcome is heart failure, a much worse prognosis than atherosclerosis. A number of diverse observations involving various forms of sulfur support the hypothesis that impaired sulfur supply to the vasculature is the key factor in cardiovascular disease. For example, early studies on primates showed that a high- fat, high- cholesterol diet fed to monkeys (not a normal diet for them!) could induce atherosclerosis, but that simultaneous supplementation with sulfur- containing nutrients was protective. Similarly, experiments on rats showed that a diet supplemented with excess cholesterol, cholic acid (a bile acid) and vitamin D2 could induce aortic lesions expressing calcification and plaque formation, but it was possible to prevent such lesions completely through simultaneous supplementation with chondroitin sulfate (a modified sugar molecule containing oxidized sulfur). As another example, children with disorders in the metabolism of cysteine (a sulfur- containing amino acid) develop atherosclerosis- like arterial damage at an early age. Interestingly, the consumption of garlic—a rich source of sulfane sulfur—is inversely correlated with the progression of cardiovascular disease. Finally and remarkably, synthetic hydrogen sulfide donors (molecules that release therapeutic hydrogen sulfide) can protect mitochondria in endothelial cells (the thin layer of cells that line the interior of blood vessels) from oxidative damage. CHOLESTEROL SULFATE SYNTHESISNormally, keratinocytes (the predominant cells found in the epidermis), red blood cells (RBCs) and platelets produce cholesterol sulfate in the skin, catalyzed by sunlight. Therefore, in accordance with my unifying theory, one would expect sunny climates to reduce heart disease risk. Indeed, geographical data show an inverse relationship between cardiovascular disease and annual sunlight availability. France and Spain have much lower rates of death from heart attacks than the United Kingdom. In a study conducted in the British Isles, mean annual sunshine hours accounted for 4. Despite related studies showing that vitamin D deficiency is associated with cardiovascular disease risk,8 placebo- controlled trials have failed to demonstrate any benefit from vitamin D3 supplementation. Why? My coauthors and I suggest that, where heart disease is concerned, the benefit of sunlight comes from cholesterol sulfate synthesis rather than vitamin D3 synthesis. In a 2. 01. 2 article in Entropy,1. The enzyme that likely carries out this function is endothelial nitric oxide synthase (e. NOS), the same enzyme that produces nitric oxide to relax the artery wall. The enzyme e. NOS is a member of the cytochrome P4. CYP) superfamily of enzymes, which metabolize drugs and synthesize cholesterol, steroids and other lipids. I hypothesize that the overuse of sunscreen has played a dual damaging role, suppressing sunlight catalysis but also actively disrupting e. NOS’s sulfate- producing function due to sunscreen’s aluminum content. Many other environmental chemicals also disrupt CYP enzymes, including mercury. Roundup. When aluminum or other toxic chemicals disable e. NOS, it is unable to make enough sulfate to supply the needs of the endothelial cells, creating a systemic sulfate deficiency problem. It is well established that e. NOS produces superoxide as well as nitric oxide, but biologists have always viewed this as a pathology. At the same time, the fact that RBCs contain abundant e. NOS baffles biologists, because nitric oxide would disrupt hemoglobin’s ability to transport oxygen. Viewing e. NOS superoxide synthesis as an alternative function to oxidize sulfur offers an explanation for both of these puzzles. GLYPHOSATE AND HYPERLIPIDEMIAGetting back to coronary artery disease, most people assume that elevated serum lipids (hyperlipidemia) are a causal factor. Tens (if not hundreds) of millions of people receive advice from their doctor to take a statin drug to protect them from heart disease because their serum lipid levels are high. Therefore, one would expect a plot over time of the hospital discharge rates for hyperlipidemia to be highly correlated with a similar plot for coronary artery disease. This is not the case, however. As the figure below shows, the correlation coefficient value is a weak 0. Although correlation does not always imply causation, it is surprising and noteworthy when a factor presumed to be causative is not correlated with the disease. FIGURE 1: Graph of incidence of hospital discharge diagnoses of hyperlipidemia (ICD 2. ICD 4. 10- 4. 14) over time from 1. CDC. In comparison, there is a very strong and highly significant correlation between hyperlipidemia and glyphosate application to corn and soy crops (R = 0. Glyphosate application rates have steadily increased over time due to the widespread appearance of glyphosate- resistant weeds growing among the crops that are increasingly engineered to be Roundup Ready. Serum lipids have risen in tandem with the increase in glyphosate use, despite the increase in statin drug prescriptions. As the second figure suggests, it is not unreasonable to propose that glyphosate is causal in hyperlipidemia. Glyphosate disrupts CYP enzyme activity in the liver, which can explain the contribution of glyphosate to hyperlipidemia. A rat study assessing the impact of glyphosate, clofibrate (a cholesterol- lowering drug) and two phenoxyacid herbicides on liver function showed that glyphosate reduced the activity of CYP enzymes in the liver much more than the other substances investigated. Multiple CYP enzymes are needed to produce bile acids,2. Bile acids normally export a large amount of cholesterol via the digestive system. Impeded bile acid synthesis due to a defective CYP7. A1 gene produced neonatal cholestasis (blocked bile ducts) and hypercholesterolemia (specifically, elevation in serum LDL) in mice fed a normal chow diet. Given that e. NOS is a CYP enzyme, it is entirely plausible that glyphosate disrupts e. NOS’s ability to synthesize sulfate. We would expect e. NOS exposure to glyphosate in the red blood cells, because glyphosate export via the kidney requires transit through the vasculature. Disrupted synthesis of cholesterol sulfate will necessitate an increase in the synthesis of LDL particles to transport cholesterol in its unsulfated form, because cholesterol is not water- soluble and therefore must be stored inside a lipid particle for transport. ATHEROMA AS ALTERNATIVE SUPPLIER OF CHOLESTEROL SULFATEIn another Entropy publication, my coauthor and I suggested that when red blood cells produce cholesterol sulfate while traversing the surface veins, catalyzed by sunlight, they release the cholesterol sulfate to the tissues in the capillaries. |
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