The mechanism of its action is identical to that of other beta-lactam antibiotics with respect to Gram-negative bacteria order cheap cyclophosphamide on-line. This product undergoes a reaction with triphenylphosphine and ethyl azodicarboxylate buy cyclophosphamide line, which results in the cyclodehydration of the product to (3S-trans)-N-benzy- loxy-3-tert-butyloxycarbonylamino-4-methyl-azetidinone (32 discount cyclophosphamide online amex. Debenzylating this by hydrogen reduction using a palladium on carbon catalyst forms (3S-trans)-N-hydroxy-3-tert- butyloxycarbonyl-amino-4-methyl-azetidinone (32 purchase cyclophosphamide now. The hydroxyl group in this com- pound is removed by reducing it with titanium trichloride, which forms azetidinone (32. Removing the tert-butyloxycarbonyl protection using trifluoroacetic acid and subsequent acyla- tion of the resulting product with the benzyl chloroformate gives (3S-trans)-benzyloxycarbony- lamino-4-methylazetidinone (32. Turning the resulting N- sulfonic acid into a potassium salt by reacting it with potassium hydrophosphate, followed by replacing the potassium cation with a tetrabutylammonium cation by reacting it with tetrabuty- lammonium sulfate gives the product (32. Reducing this with hydrogen using a palladium on carbon catalyst gives 3-amino-4-methyl-monobactamic acid (32. Acylating this with (Z) 2-amino-α-[[2-(diphenylmethoxy)-1,1-dimethyl-2-oxoethoxy]imino] 4-thiazoleacetic acid in the presence of dicyclohexylcarbodiimide and 1-hydroxy-benzotriazole gives the diphenyl- methyl ester of the desired aztreonam (32. The spec- trum of use of aztreonam is very similar to the antimicrobial spectrum of aminoglycosides, and in the majority of cases it is a potential replacement. Aztreonam is used for treating infections of the urinary tract and gastric tract, osteomyelitis, gonorrhea, intraabdominal and gynecological infections, infections of the bones, skin, etc. In patients with known or suspected combined infections, it should be used in combination with other drugs such as clindamycin, metronidazole, nafcillin, or vancomycin. They belong to a group of antibiotics known by the name macrolides, because they contain a macrocyclic lactone ring (14-membered in erythromy- cin and clarithromycin, which as a matter of fact is 6-methoxyerythromycin; and 15-mem- bered ring in azithromycin, due to the presence of an additional nitrogen atom in the ring) to which deoxysugar residues are joined. There are also known macrolides with a 12-membered lactone ring, which received the name of patulolides, as well as those with a 16-membered lactone ring, which are called isenamycins. Today, there are about 100 compounds that make up this group of macrolide antibiotics, and they are generally produced by streptomycetes. There are direct indications for their use, and at the same time they are an alternative to penicillins for those who are allergic to penicillin. Macrolides, both erythromycin and others, inhibit the synthesis of bacterial proteins. However, there is a significant difference that allows a specific antibiotic to exhibit selec- tive toxicity with respect to bacteria. Protein synthesis takes place on ribosomes, which can be rep- resented as certain machines in which proteins and various amino acids are assembled. Bacteria contain 80 S ribose, which is synthesized of two unequal components: a large 50 S subunit and small 30 S subunit. These regions are known as acceptor (A) and donor (R) regions, respectively, and they are located very close to one another. Growth of the peptide chain is accomplished by the transfer and binding of a peptide chain from region R to region A by catalysis of peptidyltransferase. Macrolides inhibit synthesis of bacterial proteins by binding with the bacterial 50 S subunit chain, thus pre- venting the growth of the peptide chain, most likely by interfering with translocation. At the same time, these drugs do not bind to ribosomes in mammals, which is a reason for their selective toxicity. Macrolides can appear as bacteriostatics as well as bactericides depending on the concentration of the drug, sensitivity of the microorganisms, their growth rate, and as a matter of fact, the size of their colony. Macrolides have a relatively broad spec- trum of use, and they are active with respect to Gram-positive and Gram-negative microor- ganisms, achiomycetes, mycoplasma, spirochaeta, chlamydia, Bacteria Rickettsia, certain mycobacteria, Colon bacillus, blue-pus bacillus, shigella, salmonella, and so on. Erythromycin: Erythromycin, (3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-4-[(2,6-dideoxy-3-C- methyl-3-O-methyl-α-L-ribo-hexopyranosyl)-oxy]-14-ethyl-7,12,13-trihydroxy- 3,5,7,9,11,13-hexamethyl-6-[[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyl]oxy ]oxacyclotetradecan-2,10-dione (32. It was first isolated in 1952 from the culture liquid of microorganisms of the type Streptomyces erytherus. Erythromycin B differs from A in that a hydrogen atom is located at position 12 in the place of a hydroxyl group, while erythromycin C differs from A in that the residue of a different car- bohydrate, micarose (2-6-di-deoxy-3-C-methyl-L-ribohexose), is bound to the macrocycle in position 3 in the place of cladinose (4-methoxy-2,4-dimethyl-tetrahydropyran-3,6-diol). Erythromycin A is produced only microbiologically using active strains of microorgan- isms of the type Saccharopolospora erythraea [188–191]. Erythromycin inhibits bacterial protein synthesis by reversibly binding with their 50 S ribosomal subunit, thus blocking the formation of new peptide bonds. However, it can also exhibit a bactericidal effect against a few types of microbes at cer- tain concentrations. Erythromycin acts on Gram-positive (staphylococci both produced and not produced by penicillinase, streptococci, pneumococci, clostridia) and a few Gram-negative microorgan- isms (gonococci, brucelli, hemophile and whooping cough bacilli, legionelli), mycoplasma, chlamydia, spirochaeta, and Rickettsia. Colon and blue-pus bacilli, as well as the bacilli shigella, salmonella, and others are resistant to erythromycin. Erythromycin is used for bacterial infections such as diphtheria, whooping cough, tra- choma, tonsillitis, scarlet fever, otitis, sinusitis, cholecystitis, pneumonia, gonorrhea, and so on. Erythromycin is an alternative to penicillin for treating infections caused by sensi- tive organisms. Clarithromycin: Clarithromycin, (2R,3S,4S,5R,6R,8R,10R,11R,12S,13R)-3-(2,6-dideoxy- 3-C-3-O-dimethyl-α-L-ribo-hexopyranosyloxy)-6-methoxy-9-oxo-11,12-dihydroxy- 2,4,6,8,10,12-hexamethyl-5-(3,4,6-trideoxy-3-dimethylamino-β-D-xylo-hexopyranosyloxy) cyclopentadecan-13-olide (32. It is presumed that its activity exceeds that of erythromycin by 2–4 times with respect to a number of streptococci and staphylococci, and to a few other microorganisms. It is used for treating bacterial bronchitis, pneumonia, skin and sexual infections. It is believed that clarithromycin is the most active macrolide for treating atypical mycobacte- ria. Antibiotics Azithromycin: Azithromycin, [2R-(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-3-(2,6- dideoxy-3-C-methyl-3- O-methyl-α-L-ribo-hexopyranosyloxy)-2-ethyl-3,4,10-trihydroxy- 3,5,6,8,10,12,14-heptamethyl-11-[(3,4,6-trideoxy-3-dimethylamino)-β-D-xylo-hexopyrano syl]-oxy]-1-oxa-6-azacyclopentadecan-15-one (32. Like other macrolides, it is active with respect to pathogens of the respiratory tract and pathogens transmitted sexually. It is used for treating bacterial bronchitis, pneumonia, skin, and sexual infections. Consequently, there were another six drugs of the tetracycline series that were introduced into medical practice between 1950 and 1972. Oxytetracycline is isolated from Streptomyces rimosus; tetracycline (semisynthetic), demeclocycline is isolated from the mutant type of S. Methods of synthesis of the tetracycline series antibiotics have been sug- gested; however, they are purely of an academic interest and do not have any practical value. Despite the few differences in these drugs in terms of pharmacokinetic features, their broad spectrum of antimicrobial action is similar in many regards. The vital element of this process is the energy-requiring transfer of the drug through the cytoplasmic membrane, which leads to its accumulation in the cell. Inside the cell, it reversibly binds with 30 S ribosomal subunits of the bacteria. The selective toxicity of tetracyclines lies in its diverse ability to penetrate bac- terial cells and mammalian cells that lack a proper system of transport. The difference is only observed in the degree of activity with respect to these or other microorganisms. Tetracyclines are active with respect to a huge variety of microorganisms, including Gram-positive, Gram-negative, aerobic, and anaerobic. They are active with respect to spirochaeta, mycoplasma, Bacteria Rickettsia, chlamydia, and a few protozoal infec- tions. However, they are not active with respect to streptococci infections, blue-pus bacillus, and a few others. Resistance to tetracyclines is exhibited as a reduced ability of bacteria to accumulate the antibiotic inside the cell. As a rule, resistance with respect to any of these tetracyclines indicates resistance to all of the others. Tetracyclines are the drug of choice with respect to a broad number of infections, including chlamydia, Bacteria Rickettsia, and others. Blue-pus bacillus, proteus, serracia, most strains of Bacteroides fragilis, most fungi, and small viruses are resistant to this drug. It is used for pneumonia, bronchitis, empyema of the lungs, angina, cholecystitis, whooping cough, endocarditis, endometritis, intestinal infections, prostatitis, syphilis, gonorrhea, brucellosis, osteomyelitis, purulent infections of soft tissues, and others caused by microorganisms sensitive to this drug. Antibiotics synthesized biosynthetically as a result of the activity of actinomycete S. However, it can be synthesized microbiologically using the actinomycete Streptomyces viridifaciens,as well as a certain mutant S.

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The immune deficiency caused by stress and sugar coupled with poor sanitation and poor life style allowed for a pathogen to become opportunistic grow to large numbers and over take people’s immune systems generic 50mg cyclophosphamide with amex. Immuno Weakness in the Middle Ages The earliest experiences the English had of refined sugar was when Crusaders brought sugar home with them after their campaigns in the Holy Land buy cyclophosphamide 50 mg without a prescription, where they encountered caravans carrying "sweet salt" purchase cyclophosphamide 50mg free shipping. Crusade chronicler William of Tyre described sugar as "very necessary for the use and health of mankind buy cyclophosphamide 50 mg on-line. There were plagues that followed the crusaders home but it was there supply of sugar that made it possible. Sugar is one of the oldest and best documented of all of the medieval commodities. Exactly what form, quality and price this commodity acheived could be variable enough to create material for disagreement whenever the product is discussed. However, an Elizabethian ate so much refined, white sugar, that the English were noted for their bad teeth and the sweetmeats that they consumed. For all the many countries and times between conditions of the sugar varied considerably. With the following information I hope to establish the cost, quality, and availablity of sugar. Alexander spread dextrose sugar cane through Persia and introduced it in the Mediterranean. The main requirements of the West were spices, perfumes, jewels and fine textiles, but lesser luxuries, such as sugar, rice and ghee were also exported. Prior to this, the juice was used much like honey, as a sweetener for food and drinks. We now know that there was a lot more contact from India through the Mediterranean world than was previously thought. An example of this is the manner in which Indian literature found its way to the Western countries. The latifondi were divided among freed serfs and smallholders, and agriculture received the greatest impetus it had ever known. Thanks to a Moslem custom, uncultivated land became the property of whoever first broke it, thus encouraging cultivation at the expense of grazing. Practically all the distinguishing features of Sicilian husbandry were introduced by the Arabs: citrus, cotton, carob, mulberry, both the celso, or black and the white morrella-sugar cane, hemp, date palm, the list is almost endless. They brought the knowledge of how to cultivate sugar cane and crush it with mills... Arab-Norman Trade Death "The so-called Dark Ages were lighter than we used to believe, and there was a constant interchange of knowledge and ideas between the supposedly hostile worlds of the Cross and the Crescent.... The Chevron, or zig-zag, provides an excellent example, for it decorates many a Sicilian door and window. This was the chevron, or zig-zag, a motif whose fecundity was such that it spread virtually everywhere... After Roger de Hauteville was crowned King of Sicily in 1130, he recognized quickly that he would need Arab support to survive. According to Norwich, in "The Kingdom In The Sun 1130- 1194", "There would be no second class Sicilians. Everyone, Norman or Italian, Lombard or Greek or Saracen, would have his part to play in the new state.... Special Saracen brigades were established in the army, quickly earning a reputation for loyalty and discipline which was to last over a hundred years. A hundred years later, (Palermo fell in 1072, so this would be 1172) Christians and Saracens were living side-by-side, amicably enough... In the "Epistola ad Petrum" in 1194, the author describes the area around Palermo lovingly, including, "vines, vegetables, fruit trees, sugar-canes and date-palms". The Arabs and following them, the Normans seem to have had no trouble enjoying the sweet profits of Sugar and its export in all forms in the 12th century. Its guards surrendered to our soldiers themselves, their beasts of burden, and sumpter horses; and stretching forth their hands in supplication, they implored for mercy, on condition only that their lives should be spared. They led the yoked horses and camels by the halter, and offered them to our men, and they brought mules loaded with spices of different kinds, and of great value; gold and silver; cloaks of silk; purple and scarlet robes, and variously-ornamented apparel, besides arms and weapons of divers forms; coats of mail, commonly called gasiganz; costly cushions, pavilions, tents, biscuit, bread. Following the example of Pope Gregory, our predecessor of pious memory, we have placed under sentence of excommunication all those who in future consort with the Saracens, directly or indirectly, or who attempt to give or send aid to them by sea, as long as the war between them and us shall last. But our beloved sons Andreas Donatus and Benedict Grilion, your messengers, recently came to the apostolic see and were at pains to explain to us that by this decree your city was suffering no small loss, for she is not devoted to agriculture but rather to shipping and to commerce. We, therefore, induced by the paternal affection we have for you, and commanding you under pain of anathema not to aid the Saracens by selling or giving to them or exchanging with them iron, flax, pitch, pointed stakes, ropes, arms, helmets, ships, and boards, or unfinished wood, do permit for the present, until we issue further orders, the taking of goods, other than those mentioned, to Egypt and Babylon, whenever necessary. We hope that in consideration of this kindness you will bear in mind the aiding of Jerusalem, taking care not to abuse the apostolic decree, for there is no doubt that whosoever violates his conscience in evading this order will incur the anger of God. For the duties on sugar for that which is imported and exported by land and by sea, the rule commands that one should take per hundred, 5 B. For the duty on sugar which is brought by beasts of burden the rule commands that one should take 1 raboin per load as duty. It is understood that the rule commands that one should take on Nabeth sugar, an internal tax. This indicates that the sugar was produced as cane in the manor system, processed into sugar at the castle, then shipped into Europe to be sold for cash to swell the Hospitallers coffers. Mack Smith, and Christopher Duggan, and "The rural interests of citizens received further protection from royal officials in 1243 over an ancient right to cut canes in the sugar plantations for use in their vineyards and pasture for their tamed bulls" adds Donald Matthew in "The Norman Kingdom of Sicily". This was because some part of his revenue came from taxes levied on processed sugar. According to A List of the Tolls at the Port of Colibre, in 1252, Colibre, a small island off the northeast coast of Spain, and under the jurisdiction of Rousillon in the thirteenth century, gave a list of what tolls were to be charged for what products. A cargo of mastic---2 solidi A cargo of gum---2 solidi A cargo of sugar---2 solidi A cargo of red dye---2 solidi A cargo of blue dye---2 solidi A bundle of leather---2 solidi...... Also lump sugar, basket sugar, rock candy, rose sugar, and violet sugar , from Cairo and Damascus. This is the first marketing of powdered sugar (finely granulated) I have found, though the Sicilian manufacture of it above would strongly suggest it previous to this. The list has "Dots" next to those items which are high cost/low volume or, as they were called "minute spices". It seems to have travelled across the south in bubonic form during the summer months of 1348, before mutating into the even more frightening pneumonic form with the onset of winter. It hit London in September 1348, and spread into East Anglia all along the coast early during the new year. By spring 1349, it was ravaging Wales and the Midlands, and by late summer, it had made the leap across the Irish Sea and had penetrated the north. Whether they caught the plague by this action, or whether it found its way north via other means, it was taking its revenge on Scotland by 1350. It would be fair to say that the onset of the plague created panic the length and breadth of Britain. It is very difficult for us to imagine the impact of plague on these small rural communities, where a village might have no more than 400 or 500 inhabitants. Few settlements were totally depopulated, but in most others whole families must have been wiped out, and few can have been spared some loss, since the plague killed indiscriminately, striking at rich and poor alike. This price seems very high, since even as far away as England, 11 pence could buy you a full pound, by then. Important Facts about the Black Death Interesting information and important facts and history of the disease:  Key Dates relating to the event: Dextrose sugar becomes cheap and plentiful in about 1310. This terrible plague started in Europe in 1328 and lasted until 1351 although there were outbreaks for the next sixty years  Why was the disease called the Black Death? The disease was called the Black Death because one of the symptoms produced a blackening of the skin around the swellings. People became disillusioned with the church and its power and influence went into decline. This ultimately resulted in the English reformation Black Death Symptoms The symptoms of the Black Death were terrible and swift:  Painful swellings (buboes) of the lymph nodes  These swellings, or buboes, would appear in the armpits, legs, neck, or groin  A bubo was at first a red color.

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