تويت
السلام عليكم ورحمة الله وبركاته
أنا طالب بالكليه بالسنه الاخيره
وانتهيت من تجميع المراجع لبحث تخرجي
الي بعنوان {أخطر الميكروبات المقاومه للمضاد الحيوي}
أبغى خطوات تجربه تنمية Staphylococcus aureus
لاني شفت صور تجربه في موضوع عوني يوسف
بصراحه كانت رائعه
بس ابغى الخطوات
وابغى اقتراحاتكم قيمه حتى يكون بحثي مميز
ثاني طلب
ماعليكم امر
فيه ترجمه لهذا المقطع او فيه احد عنده نفس الموضوع بالعربي
•
Mechanism of action of the quinolone antibiotics
Quinolone are usually bactericidal in action . They act on both multiplying (logarithmic phase )and resting (stationary phase ) bacterial cells . they function by inhibiting DNA synthesis in susceptible organisms via inhibition of the enzymatic activities of 2 chemically related members of the DNA topoisomerase class of enzymes , DNA gyrase , a type II topoisomerase IV . DNA gyrase and topoisomerase IV have distinct essential roles in bacterial DNA replication . DNA gyrase was the first identified quinolone target and it introduces negative super-helical twists in DNA , by nicking and sealing DNA during replication . Removing positive superhelical twists is an important activity for initiation of DNA replication . It also results in the highly condensed 3-dimensional structure of the genetic material by packing it inside the cell . In E.coli , for example , a DNA strand of around 1300 m m long . Without the gyrase ,DNA cannot be replicated ,and then repacked in daughter cells Topoisomerase IV acts at the terminal states of DNA replication by allowing for separation of interlinked daughter chromosomes so that segregation into daughter cells can occur . fluoroquinolones inhibit these topoisomerase enzymes by stabilizing either the DNA—DNA gyrase complex or the DNA—topisomerase IV complex : these stabilized complexes block movement of the DNA replication fork and thereby inhibit DNA replication resulting in cell death .
Although all fluoroquinolones generally are active against both DNA gyrase and topoisomerase IV the drugs differ in their relative activities against these enzymes. For many Gram-negative bacteria , DNA gyrase is the primary quinolone target and for many Gram-positive bacteria , topoisomerase IV is the primary target the other enzyme is the secondary target in both cases . However , there are exceptions to this pattern . For certain e.g. streptococcus pneumonia , the principal target depends on the specific fluoroquinolone . Gemifloxacin is promoted by genesoft pharmaceuticals as providing a"double punch " against this organism , as it binds with both enzymes (double targeting)
Although human cells do not contain DNA gyrase , they do contain a topoisomerase enzyme that functions in the same manner . this mammaliam enzyme is not affected by bactericidal concentrations of quinolones . To illustrate this point ciprofloxacin for example ,is Known to have 100 times higher affinity for bacterial DNA gyrase than for bacterial DNA gyrase than for mammalian topoisomerase .
Bacteria may become resistant to quinolones by alterations in the permeation of the drug through the outer cell membrane , by mutations in the gene sequences that transcribe the quinolone target molecules by increased active drug efflux , or by acombination of these mechanisms . Antibacterial potency is defined in part by the quinolone affinity for DNA gyrase and topisomer IV , and quinolones differ in their affinity for each 2 target enzymes . clinically detectable fluoroquinolone resistance is most commonly mediated through alteration of both targets . spontaneous nucleic acide substitutions occur in the genes that encode the DNA gyrase and topoisomerase IV subunits .
MECHANISM OF ACTION
Polyene antifungals are usually fungistatic in action at the concentrations obtained clinically , but may be fungicidal in high concentration or against very susceptible organisms . the hydrophobic heptaene part of the molecule interacts strongly with the similarly hydrophobic ergosterol within the fungal cell membrane .the hydrophilic polyol region of the molecule , on the other hand , forms channels in the membrane that allow the uncontrolled leakage of inorganic cations out of the fungus eventually leading to cell death . since polyenes have higher affinity for ergosterol than cholesterol (cholesterol is the dominant sterol in the cell membranes of animal cell )they preferentially bind to fungal cell . But as selectivity is limited , toxicity might extend to mammalian cell , if the dose is not controlled . in fact polyenes posses generally a high level of toxicity to humans and binding to sterols in mammalian cells (such as certain kidney cells and erythrocytes) may account for some of the toxicities reported with conventional amphotericin B therapy . At usual therapeutic concentrations of amphotericin B , the drug does not appear to hemolyze mature erythrocytes , and the anemia seen with conventional IV amphotericin B therapy may result from the action of the drug on actively metabolizing and dividing erythropoietic cells . the above mechanism is somewhat different form that of the synthetic azoles , such as miconazole and fluconazole .
Methanism of Action OF B-lactam Antibiotics
All B-lactam antibiotics act by weekening the cell well , resulting in cell lysis and death. Their action is BACTERICIDAL and they exert it ONLY on DIVIDING or GROWING bacterial cells.Bacterial cell thet don,t divide (resting) are not harmed by B-lactam antibiotics.Accordingly, it is contraindicated to prescribe a bacteriostatic agent ,like a tetracycline , with a B-lactam antibiotic , which then becomes useless. (notice that we said B-lactam antibiotic ,we did not say bactericidal antibiotic .what is the difference?)
The exact course of action that is followed differs from Gram-positive to Gram-negative bacteria. In Gram-positive bacteria, as a cell divides and the two daughter cells separate,part of the cell wall will be synthesized in the presence of the B-lactam antibiotic.this part will be weak and defective.As the organism undergoes further division ,an additional area of the cell wall will again become defective,aweak spot will be formed on the cell well,which expands a little forming a small bubble. Following repeated cell divisions a group of bubbles will formed leading to the so called"mulberry Appearance",as shown below.the cell wall at this stage is very weak and at any moment it would undergo lysis and death. The cell wall lysis is due to the high internal osmotic pressure. Gram-positive cells possess high osmotic pressure as they tend to hoard or store many nutrients inside them, which they are unable to synthesize themselves. The whole processes can be illustrated in the following presentations:
In Gram-negative bacteria the behavior is different , because they are more advanced then Gram-positive bacteria. They don’t need to store as many nutrients, because they can synthesize their own. Hence their internal osmotic pressure is less.upon dividing in the presence of a B-lactam antibiotic,the weekened part of the cell wall reacts by expanding ,rather then the formation of a bubble. Expansion continues upon further cell division ,resulting in the end of a"filamentous appearance". At this point the weakened cell wall become ready to undergo lysis and death
مع العلم اني حاولت اترجمها اكثر من مره بس بلا جدوى
أتمنى اي احد عنده خبره بالموضوع يفيدني
لان هذا اخر خطوه من تجميع مراجع البحث
وأتمنى التوفيق للجميع :sm183:
و
ولاتنسونا من صالح الدعاء
أنا طالب بالكليه بالسنه الاخيره
وانتهيت من تجميع المراجع لبحث تخرجي
الي بعنوان {أخطر الميكروبات المقاومه للمضاد الحيوي}
أبغى خطوات تجربه تنمية Staphylococcus aureus
لاني شفت صور تجربه في موضوع عوني يوسف
بصراحه كانت رائعه
بس ابغى الخطوات
وابغى اقتراحاتكم قيمه حتى يكون بحثي مميز
ثاني طلب
ماعليكم امر
فيه ترجمه لهذا المقطع او فيه احد عنده نفس الموضوع بالعربي
•
Mechanism of action of the quinolone antibiotics
Quinolone are usually bactericidal in action . They act on both multiplying (logarithmic phase )and resting (stationary phase ) bacterial cells . they function by inhibiting DNA synthesis in susceptible organisms via inhibition of the enzymatic activities of 2 chemically related members of the DNA topoisomerase class of enzymes , DNA gyrase , a type II topoisomerase IV . DNA gyrase and topoisomerase IV have distinct essential roles in bacterial DNA replication . DNA gyrase was the first identified quinolone target and it introduces negative super-helical twists in DNA , by nicking and sealing DNA during replication . Removing positive superhelical twists is an important activity for initiation of DNA replication . It also results in the highly condensed 3-dimensional structure of the genetic material by packing it inside the cell . In E.coli , for example , a DNA strand of around 1300 m m long . Without the gyrase ,DNA cannot be replicated ,and then repacked in daughter cells Topoisomerase IV acts at the terminal states of DNA replication by allowing for separation of interlinked daughter chromosomes so that segregation into daughter cells can occur . fluoroquinolones inhibit these topoisomerase enzymes by stabilizing either the DNA—DNA gyrase complex or the DNA—topisomerase IV complex : these stabilized complexes block movement of the DNA replication fork and thereby inhibit DNA replication resulting in cell death .
Although all fluoroquinolones generally are active against both DNA gyrase and topoisomerase IV the drugs differ in their relative activities against these enzymes. For many Gram-negative bacteria , DNA gyrase is the primary quinolone target and for many Gram-positive bacteria , topoisomerase IV is the primary target the other enzyme is the secondary target in both cases . However , there are exceptions to this pattern . For certain e.g. streptococcus pneumonia , the principal target depends on the specific fluoroquinolone . Gemifloxacin is promoted by genesoft pharmaceuticals as providing a"double punch " against this organism , as it binds with both enzymes (double targeting)
Although human cells do not contain DNA gyrase , they do contain a topoisomerase enzyme that functions in the same manner . this mammaliam enzyme is not affected by bactericidal concentrations of quinolones . To illustrate this point ciprofloxacin for example ,is Known to have 100 times higher affinity for bacterial DNA gyrase than for bacterial DNA gyrase than for mammalian topoisomerase .
Bacteria may become resistant to quinolones by alterations in the permeation of the drug through the outer cell membrane , by mutations in the gene sequences that transcribe the quinolone target molecules by increased active drug efflux , or by acombination of these mechanisms . Antibacterial potency is defined in part by the quinolone affinity for DNA gyrase and topisomer IV , and quinolones differ in their affinity for each 2 target enzymes . clinically detectable fluoroquinolone resistance is most commonly mediated through alteration of both targets . spontaneous nucleic acide substitutions occur in the genes that encode the DNA gyrase and topoisomerase IV subunits .
MECHANISM OF ACTION
Polyene antifungals are usually fungistatic in action at the concentrations obtained clinically , but may be fungicidal in high concentration or against very susceptible organisms . the hydrophobic heptaene part of the molecule interacts strongly with the similarly hydrophobic ergosterol within the fungal cell membrane .the hydrophilic polyol region of the molecule , on the other hand , forms channels in the membrane that allow the uncontrolled leakage of inorganic cations out of the fungus eventually leading to cell death . since polyenes have higher affinity for ergosterol than cholesterol (cholesterol is the dominant sterol in the cell membranes of animal cell )they preferentially bind to fungal cell . But as selectivity is limited , toxicity might extend to mammalian cell , if the dose is not controlled . in fact polyenes posses generally a high level of toxicity to humans and binding to sterols in mammalian cells (such as certain kidney cells and erythrocytes) may account for some of the toxicities reported with conventional amphotericin B therapy . At usual therapeutic concentrations of amphotericin B , the drug does not appear to hemolyze mature erythrocytes , and the anemia seen with conventional IV amphotericin B therapy may result from the action of the drug on actively metabolizing and dividing erythropoietic cells . the above mechanism is somewhat different form that of the synthetic azoles , such as miconazole and fluconazole .
Methanism of Action OF B-lactam Antibiotics
All B-lactam antibiotics act by weekening the cell well , resulting in cell lysis and death. Their action is BACTERICIDAL and they exert it ONLY on DIVIDING or GROWING bacterial cells.Bacterial cell thet don,t divide (resting) are not harmed by B-lactam antibiotics.Accordingly, it is contraindicated to prescribe a bacteriostatic agent ,like a tetracycline , with a B-lactam antibiotic , which then becomes useless. (notice that we said B-lactam antibiotic ,we did not say bactericidal antibiotic .what is the difference?)
The exact course of action that is followed differs from Gram-positive to Gram-negative bacteria. In Gram-positive bacteria, as a cell divides and the two daughter cells separate,part of the cell wall will be synthesized in the presence of the B-lactam antibiotic.this part will be weak and defective.As the organism undergoes further division ,an additional area of the cell wall will again become defective,aweak spot will be formed on the cell well,which expands a little forming a small bubble. Following repeated cell divisions a group of bubbles will formed leading to the so called"mulberry Appearance",as shown below.the cell wall at this stage is very weak and at any moment it would undergo lysis and death. The cell wall lysis is due to the high internal osmotic pressure. Gram-positive cells possess high osmotic pressure as they tend to hoard or store many nutrients inside them, which they are unable to synthesize themselves. The whole processes can be illustrated in the following presentations:
In Gram-negative bacteria the behavior is different , because they are more advanced then Gram-positive bacteria. They don’t need to store as many nutrients, because they can synthesize their own. Hence their internal osmotic pressure is less.upon dividing in the presence of a B-lactam antibiotic,the weekened part of the cell wall reacts by expanding ,rather then the formation of a bubble. Expansion continues upon further cell division ,resulting in the end of a"filamentous appearance". At this point the weakened cell wall become ready to undergo lysis and death
مع العلم اني حاولت اترجمها اكثر من مره بس بلا جدوى
أتمنى اي احد عنده خبره بالموضوع يفيدني
لان هذا اخر خطوه من تجميع مراجع البحث
وأتمنى التوفيق للجميع :sm183:
و
ولاتنسونا من صالح الدعاء
تعليق