Review articles

By Ms. Laila S Azman , Mr. Ahmad A Rahim , Mr. Soo K Fan , Mr. Muhammad H Abd Kadir , Ms. Nur A Abdul Hamid , Ms. Siti K Muhammad , Ms. Ai W Wong , Dr. Amin M Abdul Majid
Corresponding Author Dr. Amin M Abdul Majid
Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, - Malaysia
Submitting Author Ms. Laila S Azman
Other Authors Ms. Laila S Azman
School of Pharmaceutical Sciences, Universiti Sains Malaysia, - Malaysia

Mr. Ahmad A Rahim
School of Pharmaceutical Sciences, Universiti Sains Malaysia, - Malaysia

Mr. Soo K Fan
School of Pharmaceutical Sciences, Universiti Sains Malaysia, - Malaysia

Mr. Muhammad H Abd Kadir
School of Pharmaceutical Sciences, Universiti Sains Malaysia, - Malaysia

Ms. Nur A Abdul Hamid
School of Pharmaceutical Sciences, Universiti Sains Malaysia, - Malaysia

Ms. Siti K Muhammad
School of Pharmaceutical Sciences, Universiti Sains Malaysia, - Malaysia

Ms. Ai W Wong
School of Pharmaceutical Sciences, Universiti Sains Malaysia, - Malaysia


Tetracycline, Acne, Pimple, Dermatology, Antibiotic, Action

Azman LS, Rahim AA, Fan SK, Abd Kadir MH, Abdul Hamid NA, Muhammad SK, et al. The Action of Tetracycline on Acne. WebmedCentral DERMATOLOGY 2011;2(12):WMC002714
doi: 10.9754/journal.wmc.2011.002714

This is an open-access article distributed under the terms of the Creative Commons Attribution License(CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Submitted on: 18 Dec 2011 07:31:12 PM GMT
Published on: 19 Dec 2011 03:40:14 PM GMT


There are few types of acne ranging from mild to severe such as Acne Vulgaris, Acne Rosacea, Pyoderma Faciale, Gram-negative Folliculitis, Acne Conglobata and the most severe one is Acne Fulminans. Tetracycline can be used to treat acne problems and is administered orally and topically. Generally, tetracycline is bacteriostatic but can be bactericidal if given in higher dose. It is widely distributed throughout tissues and excreted unchanged via renal and biliary routes. The most common side effects are nausea, headache and staining of the teeth. Besides tetracycline, doxycycline and minocycline are also used for treatment of acne at a lower dose. Tetracycline should not be given to patients having hypersensitivity to tetracycline, pregnant women and lactating mothers. It should not be taken together with milk, antacids and oral contraceptive.


What is acne?

Acne is a common disorder affecting people of all races and ages. It is a skin condition that causes comedones (blackheads and whiteheads) and inflamed red growths (papules, pustules, and cysts), formation of nodules (large papules) and possibly scarring. It is also known as acne vulgaris or cystic acne (1, 2). Commonly, they are called pimples which usually appear on the face but they can also develop on the other parts of the body such as the back, the shoulders, neck and chest (3).
Pustule is a red circle with a white or yellow centre. A small, red, tender bump with no head is called papule. Whereas cyst is a closed sac filled with fluid, pus, or other material. Whitehead is formed when the oil breaks though to the surface. The oil changed from white to black after being oxidized and result in blackhead (4).
There are a few types of acne. The most common type of acne is Acne Vulgaris, literally means “common acne”. It is categorized as mild or moderate type. This type of acne is characterized by its different forms of lesions which include blackheads, whiteheads, papules, pustules, nodules and cysts (5). It can be treated with some simple home remedies.
Acne Rosacea usually affects people over the age of 30. It frequently occurs in women but often more severe when found in men. It looks similar to Acne Vulgaris which leads to confusion however they have distinct ways of treatment. It is manifested in the form of a red rash on the forehead, cheeks, nose and chin (6). The redness is often accompanied by bumps, pimples, and skin blemishes (5).
Pyoderma Faciale is the other type of acne. It is also known as Rosacea Fulminans. It is severe facial acne affecting only females, usually between the ages of 20 to 40 years old which comes with nodules, pustules as well as sores and may leave permanent scarring. It occurs most often in women who have never experienced acne before and fortunately it does not last longer than a year (5).
The fourth type of acne called Gram-negative folliculitis. It is a rare condition of bacterial infection that comes with long-term treatment of acne with antibiotics. It will result in pustules and cysts (7).
Acne Conglobata is the most severe type of acne and mainly affects males. It is characterized by numerous large interconnected lesions on the face, chest, back, buttocks, upper arms, and thighs and can be accompanied by numerous widespread blackheads. It leads to severe psychological as well as physical suffering since it is extremely disfiguring. To make thing worse, it causes damage to the skin and permanent scarring (7).
The last type of acne is known as Acne Fulminans. It is an abrupt onset of acne conglobata-like symptoms accompanied with fever and aching of the joints. It normally occurs in young men. Isotretinoin and oral steroids are normally prescribed to get rid of it (5, 6).
Causes of acne
The main culprit of acne is the excess production of an oily substance called sebum resulting in blockage of hair follicles. The exact cause of acne is not fully understood. However, the elements that influence its development are known. It can be due to heredity, oily skin or hair, hormonal imbalance, some prescription medications and cosmetics that contain chemicals and vegetable oil, high stress, and possibly some nutritional deficiencies (8).
Heredity or genetics is one of the factors that cause acne. Researchers believe that inheritance from parents increase the tendency of their children to develop acne (6). People with over-sensitive oil glands cause them keep on producing a higher level of sebum. Hence, their oily complexions cause them more prone to having acne (9).
Fluctuation or imbalances of hormonal levels are often regarded as the main cause of acne. It can be seen when most people start to have acne when they reach puberty which referred to teenage growth phase. During this stage, teenagers start to produce androgens. It enlarges sebaceous glands and greater amounts of sebum are produced which mix with the dead skin cells or bacteria on the skin’s surface, resulting in the pores becoming blocked. Hence, inflammation starts to occur. Acne also appears when women undergo menstruation whereby their hormone levels are imbalanced (9, 10).
In fact, dietary intake is closely related to hormonal levels. People who are more prone to acne breakouts will have higher risks to get acne when they eat more unhealthy food. This is because food with higher content of chemicals and fat contributes to hormonal imbalance which will induce ailments such as acne (10).
Besides, stress is also a factor that aggravates acne. When a person is under stress, more adrenaline hormones are produced and excessive hormones are responsible for repeated acne breakouts by reducing the nutrient-absorbing capacity of the body and immediately attacking the skin. Stress actually slows down the healing process of both severe open wounds and small acne pustules since it affects the immune system of the body. In other words, adults are more prone to stress-related acne as they at higher risk of getting stress (11).
Deficiency of certain nutrient in body especially vitamin may lead to acne aggravation. Acne development is closed related to Vitamins A, B, C, E and zinc. Vitamins act as antioxidants that assist skin in elimination of toxins and harmful free radicals. Lack of vitamins will increase the exposure of skin to toxins and bacteria that may contribute to development of acne(10).
How acne can occur?
There are many tiny holes on our skin surface called pores. Each pore will grow a hair which known as hair follicle. The hair follicles in our skin are connected with oil glands called sebaceous glands. The sebaceous glands produce sebum that helps to lubricate the skin by keeping the skin surface oily and protecting the skin. On the other hand, dead skin cells shed away from the pore lining whereas sebum is being distributed to the exterior surface of the skin (8, 12).
In normal skin, the pore is open and the right amount of sebum secreted will come out on the skin surface. However, when too much of oil/sebum is produced, the pores get clogged up. The blockage of pore also called plug. The plug traps the dead skin cells, dirt and debris within the hair follicles. This will prevent the sebum from leaving the pores which results in bacteria as well as inflammatory cells building up underneath the skin. Subsequently, the skin swells and red bumps are formed. These indicate the formation of acne. If the inflammation is deep in the skin, the pimples will enlarge to form cysts (1). The acne lesions we know as whiteheads and blackheads are called “comedones”. Red, swollen, pus-filled lesions are called papules, nodules, and pustules (13). We can also conclude that areas where a lot of sebaceous glands are present tend to have higher chance to develop acne as the blockage of pores may occur frequently.

Common Uses Of Tetracycline

Other than acne, tetracycline is widely used against other bacterial infection because of its wide spectrum activity such as infection caused by ticks, Lyme disease and Rocky Mountain spotted fever(RMSF) (14). Lyme disease is the most common tick-borne disease caused by bacteria which belong to the genus of Borrelia. The RMSF caused by bacteria Rickettsia rickettsii is a lethal condition and tetracycline must be given instantly. Doxycyline is usually used in treatment of Lyme disease and RMSF (15).
Tetracycline is also used in the treatment of urinary tract infection (UTI). Urinary tract infection is one of the most commonly found infection in developed countries, and it is eight or nine times more frequent among women than men especially elderly women (16). Besides, sexual intercourse is also one of the risk factor. The types of bacteria include E. coli, Klebsiella, Proteus, Pseudomonas, Serratia, and enterococcus but rarely include anaerobes.
In addition, tetracycline is widely used in the treatment of Helicobacter pylori infections. It is a gram-negative bacterium found in human stomach which causes gastritis and gastric ulcers. In serious condition, it can lead to duodenal ulcers and stomach cancer. Tetracycline is usually combined with antacids, H2-antagonists or proton pump inhibitors to kill the Helicobacter pylori.
Moreover, tetracycline is the preferred choice of treatment for patients who develop resistance to the penicillin such as Anthrax, Gonorrhea and Syphilis (17)

Some of the common uses of tetracycline are shown in Table 1.

Mechanism of Action of Tetracycline

Tetracycline is generally bacteriostatic against most organisms, but high concentrations of tetracycline can be bactericidal. The structure of tetracycline can be seen in the Figure 1. The antimicrobial action of tetracycline in acne occurs via protein synthesis inhibition. It acts by binding to the 30S subunit of the microbial ribosome. Tetracycline gains access to the ribosome after passive diffusion through porin channels in the bacterial membrane. An active transport process also exists in bacterial cells. During protein biosynthesis, the new t-RNA with the amino acid will try to bind to A-site of the ribosome. However, since the A-site is blocked by the tetracycline, the aminoacyl-tRNA cannot bind to it. Thus without the sequential attachment of the tRNA at the A-site, protein biosynthesis cannot occur. By inhibiting the protein biosynthesis process, tetracycline will cause cell death of the bacterial cell. This action is usually inhibitory and reversible upon withdrawal of the drug. Mammalian cells are not affected by tetracycline because they do not contain 30S ribosomal subunit (18).
Tetracycline, by targeting problematic surface bacteria, inhibits production of bacterial products that stimulate inflammation. Tetracycline will cause down-regulation of proinflammatory cytokines (ie,TNF-a, IL-1b, IL-6), production of anti-inflammatory cytokine (ie, IL-10) secretion and reduction in antibody production (19)




Mechanism of Resistance of Tetracycline

Tetracycline is a bacteriostatic agent which has a wide spectrum of uses itherapeutically. In general, it acts on bacteria by stopping the protein synthesis to inhibit the growth of the bacteria. The use of this antibiotic is very famous since it has broad spectrum activity and low toxicity. However, the bacteria could evolve and become resistant to the antibiotic (20). The emergence of tetracycline-resistant bacteria has resulted in the decrease and limit of the therapeutic action of tetracycline. Indeed, tetracycline resistance in many commensal and pathogenic bacteria has emerged now due to genetic achievement of tetracycline resistance genes (21). Recently, three difference specific mechanisms of tetracycline resistance are found - tetracycline efflux, ribosome protection and tetracycline modification (22).
Emergence of the tetracycline resistance is primarily due to possession of genetically mobile tetracycline resistance genes, which encode proteins that confer ef?ux of tetracyclines, or ribosomal protection (21). These first two mechanisms are the most common and most of their genes are usually attained via transferable plasmids and/or transposons. The presence of both mechanisms in aerobic and anaerobic Gram-negative or Gram-positive bacteria indicates their wide distribution among the bacterial kingdom (21).
In tetracycline efflux, its genes code for membrane-associated proteins, which export tetracyclines from the cell major facilitator superfamily (MFS) (23). Tetracycline efflux mechanism is an approach to limit the access of tetracycline to ribosome which can inhibit protein synthesis of the bacteria (22). The result from the export of tetracycline will reduce the intracellular drug concentration and thus, protects the ribosomes within the cell (23). The resistance gene product is a cytoplasmic membrane protein that is an energy-dependent tetracycline transporter (22).
The other type of tetracycline resistance mechanism is ribosomal protection protein. This is the least familiar mechanism, however it is probably more widespread than tetracycline efflux (24). The protein called cytoplasmic protein interacts or associates with the ribosome, making it insensitive to tetracycline inhibition (21, 22). Ribosome protection is mediated by a soluble protein which shares homology with the GTPases participating in protein synthesis, namely EF-Tu and EF-G (25, 26). At the N-terminal area, the greatest homology is seen which contain the GTP-binding domain (25). Thus, the RPPs bind and hydrolyze GTP in a ribosome-dependent manner, and maintenance of this activity is important for in vivo activity (27). The mechanism of ribosomal protection works in vivo and in vitro, unlike the action of ef?ux proteins; which require intact membranes to function (21). On the other hand, the RPPs may be evolutionarily derived from the elongation factors, such that they lost their original function and have been adapted to function in tetracycline resistance (27).
The third mechanism of tetracycline resistance is tetracycline modification. This reaction only works in aerobic environment, in the presence of both oxygen and NADPH and does not function in the natural host (Bacteroides) (21, 22). There is only one type of gene encodes the tetracycline resistance due to enzymatic alteration of tetracycline that is the tet(X) gene. Its product is a 44-kDa cytoplasmic protein that chemically modifies tetracycline (21). The tet(X) gene is classified according to the resistance gene which shares amino acid homology with a number of NADPH-requiring oxidoreductases, particularly in the region containing the NADPH-binding site (22, 28). However, the clinical significance of tet(X) is still unclear nor confer resistance on the Bacteroides strains in which it was originally found, but it requires such high levels of ventilation so it probably could not confer meaningful levels of resistance in the microaerophilic environment found in most sites on the human body (22).

Pharmacokinetics Profile of Tetracycline

Administration: Tetracycline can be given orally, periodontally, ophthalmic (eyes) or topically (29). However, in order to treat acne vulgaris, oral tetracycline is usually prescribed (30).
Absorption: Oral tetracycline has relatively high absorption in GIT which is 77-88% (30). It has high solubility but quite poor permeability (30). Absorption of tetracycline is reduced by administration with food, iron and milk (31). This is because iron, calcium, magnesium and aluminium will chelate tetracycline in GIT, hence reducing its absorption(30).
Distribution: Tetracycline is widely distributed throughout the tissues (30). However, since it is not highly lipophilic, it may not optimally penetrate the follicular unit (30). This is due to the fact that follicular unit contains high amounts of lipid-rich sebum (30).
Metabolism: Tetracycline does not undergo any metabolism(32).
Excretion: Tetracycline is excreted unchanged via renal and biliary routes (32). About 50% of the drug is excreted through glomerular filtration (32).

Side Effects of Tetracycline

Every medication has its own side effect. The same goes to tetracycline. If the side effect is severe, then stop using the medication.
The common mild side effects of using tetracycline are stinging, redness, burning, peeling, and itchiness. Any allergic reaction towards tetracycline can be considered as severe side effects and its usage should be stopped.
The other possible mild side effects of taking tetracycline include nausea, headache, stomach cramp, and vomiting (33). Indigestion, abdominal upset, gastrointestinal irritation (severe), rashes (rare, severe if they manifest), phototoxic reactions (oversensitivity to sunlight), the increased incidence of candidal valvovaginitis, severe headaches, hives, drug-induced hepatitis are also some of the side effects of using tetracycline. Skin, nails and eyes may become yellow or known as jaundice (34).
The side effects are not similar to all the patients. It is dependent on the condition of a patient and how his body tolerates tetracycline.
Results of a study done in 2004 indicated that tetracycline as well as other tetracycline derivatives may well be responsible for staining of the teeth as well as the oral cavity. Besides staining of the oral cavity and teeth, further research indicated that acne treatments containing cyclones may also cause adverse drug reactions (36). Tetracycline should not be used in children because it can cause permanent discoloration of the natural hue of the teeth (yellowing). The same goes to the pregnant women. They cannot use tetracycline during pregnancy because the fetus may experience slower bone growth. Their teeth may also be affected once they are born (34).
Tetracycline may also increase the risk of autoimmune disorders, hypersensitivity syndromes and abnormal skin pigmentations. A reported released by a university in Germany indicates that side effects related to the use of tetracycline may include contraction of Sweet's syndrome. Sweet’s syndrome is a condition in which painful red nodules arise on various parts of the body and is also generally accompanied by fever and malaise (38).
A study published by a hospital in France in May of 2003 indicates that ‘adverse affects of cyclines might be serious and sometimes unknown.’ The report further suggested that ‘long term treatment by tetracycline must be researched in patients presenting such symptoms.’ Symptoms related to adverse side effects in nearly 250 cases included autoimmune disorders, hypersensitivity syndromes as well as abnormal skin pigmentations (37).
A report released in February of 2000 indicated that tetracycline could also be responsible for the induction of intracranial hypertension (39).
Research indicates that patients who are considering the use of tetracycline to consider the risks associated with this acne treatment before proceeding with use(35).

Formulations of Tetracycline

The oral dose of tetracycline for treating acne is from 125mg to 500mg depending to the severity of the acne. Beside tetracycline, doxycycline and minocycline are also used for treatment of acne at a lower dose (40). Table 2.1 shows a list of tetracycline, minocycline and doxycycline product available in Malaysia. While Table 2.2 shows the international listing of tetracycline, minocycline and doxycycline brand name.
Most oral tetracycline is formulated into capsule or tablet form which gives tetracycline a better stability to the tetracycline when taken orally. This is because tetracycline degrades to epitetracycline due to epimerization in protic solvent which cause the tetracycline to be inactive (40). Besides that, the release of tetracycline is controlled when it is given in tablet or capsule form over its solution form (40).
Beside oral route, tetracycline is also formulated for topical route. The dosage forms used are cream, ointment and gel (40). The topical form of tetracycline is mostly applied to a small area affected by acne because usage over a larger area has been proven to be awkward (40). Besides that, topical application of tetracycline could avoid the gastrointestinal disturbance caused by the drug and drug interactions which may occur if taken orally. The first stable topical tetracycline produced was in ointment form because tetracycline is relatively stable in the ointment base (40). However for cosmetic use, the oily formulation is less desirable thus the formulation of a less greasy cream was created. Finally the gel formulation of tetracycline was created which is stable, non-greasy, less irritating and soft for the skin (40).

Drugs Interactions And Contraindications

Tetracycline is contraindicated in patients known to have tetracycline hypersensitivity (47).
Tetracycline is bacteriostatic. So, tetracycline must not be given in conjunction with penicillin or other bactericidal antibiotics because it may disturb the bactericidal action of penicillin (49). Bacteriostatic and bactericidal antibiotics should not be used together since the bactericidal agents, for example, penicillins may be inhibited by the bacteriostatic agent too (48).
Treatment with tetracycline can alter the normal flora of the colon and allow overgrowth of Clostridium difficile. Hence, the patient may suffer from diarrhea during treatment. Symptomatic of Clostridium difficile-associated disease, pseudomembranous colitis, may also occur in the initial weeks of the following treatment. If patient is suspected to have pseudomembranous colitis, tetracycline should be stopped immediately and the patient should be treated with supportive and specific treatment without delay. Any products that inhibit peristalsis are contraindicated in this clinical situation (47).
There are some compounds that may interfere with the bioavailability of tetracycline antibiotics. These include antacids; sucralfate; magnesium salicylate; magnesium citrate; polysaccharide-iron complex; quinapril (tablets contain magnesium); and multivitamins that contain iron, calcium, manganese, or zinc. Laxative preparations containing magnesium are also contraindicated. So, tetracycline should not be given with or within 4 hours of any of the above drugs. Besides, calcium salts and magnesium salts that are contained in food and dairy products can form chelates with tetracycline and decrease the absorption. Administration of tetracycline at least one hour prior to or two hours after a meal and/or milk will reduce the effect (47).
Warfarin has shown a clinically significant interaction with tetracycline because the action of warfarin and other oral anticoagulants are increased by either impairing prothrombin utilization or decreasing production of vitamin K (48).
Tetracycline should not be used with acitretin, isotretinoin, strontium, and tretinoin that are taken orally because very serious interactions may occur.
Zinc can affect tetracycline because it can attach to tetracycline in the stomach. This reduces the amount of tetracycline absorbed. Thus, it will decrease the effectiveness of tetracycline too (49).
Tetracycline may chelate the divalent or trivalent cations, forming insoluble compounds (50).
Tetracycline bioavailability may be decreased by didanosine, due to the buffering agents in didanosine tablets or powder. Some antidiarrheals that comprise of cations will form chelated compounds too (50).
Concurrent use of tetracycline with oral contraceptives may make the oral contraceptives less effective (50). This is due to stimulation of estrogen metabolism or a decline in estrogen enterohepatic circulation via changes in gastrointestinal flora (48).
Topical tetracycline preparations contain sodium sulfites while oral dosage forms may contain tartrazine dye. More precaution steps should be considered when dealing with patients with a known sulfite hypersensitivity or tartrazine dye hypersensitivity. Sensitivity reactions are prone to have happen in asthmatic than in non-asthmatic patients (50).
If a pregnant mother wants to use the tetracycline, she should know that all tetracyclines have a harmful effect on the skeletal development and bone growth of the fetus or child. Therefore, tetracycline should not be used in the second half of pregnancy unless there are more benefits from treatment to the mother compared to the risk of fetus, but their use should be considered only with extreme caution (47).
Although tetracycline can form non absorbable complexes with the calcium in breast milk, tetracycline is distributed into breast milk. Therefore, breast-feeding mothers should not use tetracycline antibiotics because risks o) teeth discoloration, enamel hypoplasia, inhibition of linear skeletal growth, oral and vaginal thrush, or photosensitivity reactions can happen in the nursing infant (47).
Dosage and frequency of tetracycline must be adjusted if given to patients with severe renal disease because some of the tetracycline is excreted in unchanged in the urine (47).Dose adjustment may be required in patients with hepatic disease too because some tetracycline is excreted via bile. The excretion process can be delayed in these patients (47).It has been reported that fatal renal toxicity can occur with the concurrent use of tetracycline and methoxyflurane (50).


Tetracycline is one of the antibiotics that can treat acne and it can be given orally or topically. All the do’s and don’ts of tetracycline must be followed to ensure the effectiveness of the antibiotic. The number of bacteria in and around the follicle can be decreased by using the antibiotic. Antibiotic can also decrease the irritating chemicals produced by white blood cells and reduce the concentration of free fatty acids in the sebum, thus reducing the inflammatory response (51). Finally this results in fewer pimples and less redness. If left untreated, acne can lead to a number of problems such as pain, infections, and scarring (52).


We would like to acknowledge and extend our heartfelt gratitude and appreciation to the following persons who have made the completion of this report possible to be done successfully. Special thanks to Dr. Amin Malik Shah bin Abdul Majid, Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia for his vital encouragement and support throughout the period of time as our supervisor.Not only that, we thankful for the constant reminders and much motivation from him.
Besides, we also want to thank all of FAR 241 Antimicrobial Therapy lecturers; which they taught us the concept of antimicrobial therapy in pharmacy field and special thanks to Lydia Pang Kai Tsan for helping us checked the grammatical errors in our report.
We would also like to forward our thanks to those contributed accidentally or in-accidentally throughout this report. On top of that, we would like to express our appreciation to all group members that fully contributed and committed in making this report succeed.


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52. Monson K, Schoenstadt A. Tetracycline for Acne. [homepage on the Internet]. January 2010 [cited 2011 Dec 10]. Available from:

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3 reviews posted so far

The Action of Tetracycline
Posted by Dr. William J Maloney on 03 Oct 2012 05:40:04 PM GMT

Posted by Dr. Ebtisam Elghblawi on 22 Dec 2011 07:26:31 AM GMT

The action of trtracycline on acne
Posted by Prof. Valcinir Bedin on 20 Dec 2011 12:56:32 PM GMT

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Accepted title. Posted by Dr. Ebtisam Elghblawi on 19 Dec 2011 08:36:26 PM GMT

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WebmedCentral Article: The Action Of Tetracycline On Acne

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