Fwd: Neuroprotective effects of Minocycline

[Guest guest]

> 1: JAMA. 2005 Apr 27;293(16):2003-11.

> Neuroprotective and anti-human immunodeficiency virus activity of

minocycline.

> Zink MC, eta ll Department of Comparative Medicine, s Hopkins

University School of Medicine, Baltimore, Md 21205, USA. mczink@

>

>

> CONTEXT: The prevalence of human immunodeficiency virus (HIV)

central

nervous system (CNS) disease has not decreased despite highly active

antiretroviral therapy. Current antiretroviral drugs are expensive,

have

significant adverse effects including neurotoxicity, and few cross

the

blood-brain barrier.

>

> OBJECTIVE: To examine the ability of minocycline, an antibiotic

with

potent anti-inflammatory and neuroprotective properties, to protect

against encephalitis and neurodegeneration using a rapid, high viral

load simian immunodeficiency virus (SIV) model of HIV-associated CNS

disease that constitutes a rigorous in vivo test for potential

therapeutics.

>

> DESIGN AND SUBJECTS: Five SIV-infected pigtailed macaques were

treated

with 4 mg/kg per day of minocycline beginning at early asymptomatic

infection (21 days after inoculation). Another 6 macaques were

inoculated with SIV but remained untreated. Blood and cerebrospinal

fluid (CSF) samples were taken on days 7, 10, 14, 21, 28, 35, 43, 56,

70, 77, and 84, and all macaques were humanely killed at 84 days

after

inoculation, a time that corresponds to late-stage infection in

HIV-infected individuals.

>

> MAIN OUTCOME MEASURES: Blood and CSF samples were tested for viral

load by real-time reverse transcription-polymerase chain reaction and

levels of monocyte chemoattractant protein 1 were quantitated by

enzyme-linked immunosorbent assay. The presence and severity of

encephalitis was determined by microscopic examination of tissues.

Central nervous system inflammation was further assessed by measuring

infiltration and activation of macrophages, activation of p38

mitogen-activated protein kinase and expression of amyloid precursor

protein by quantitative immunohistochemistry.

>

> RESULTS: Minocycline-treated macaques had less severe encephalitis

(P

= .02), reduced CNS expression of neuroinflammatory markers (major

histocompatibility complex class II, P = .03; macrophage marker

CD68 , P

= .07; T-cell intracytoplasmic antigen 1, P = .03; CSF monocyte

chemoattractant protein 1, P = .001), reduced activation of p38

mitogen-activated protein kinase (P<.001), less axonal degeneration

(beta-amyloid precursor protein, P = .03), and lower CNS virus

replication (viral RNA, P = .04; viral antigen, P = .04). In in vitro

analysis, minocycline suppression of HIV and SIV replication in

cultured

primary macrophages did not correlate with suppression of activation

of

p38-mitogen-activated protein kinase pathways, whereas suppression in

primary lymphocytes correlated with suppression of p38 activation.

>

>

>

> CONCLUSIONS: In this experimental SIV model of HIV CNS disease,

minocycline reduced the severity of encephalitis, suppressed viral

load

in the brain, and decreased the expression of CNS inflammatory

markers.

In vitro, minocycline inhibited SIV and HIV replication. These

findings

suggest that minocycline, a safe, inexpensive, and readily available

antibiotic should be investigated as an anti-HIV therapeutic.

> PMID: 15855434 [PubMed - indexed for MEDLINE]

>

>

Prog Neuropsychopharmacol Biol Psychiatry. 2007 Jan 30;31(1):304-7.

Epub

2006 Oct 5. Related Articles, Links

Click here to read

Possible antipsychotic effects of minocycline in patients with

schizophrenia.

Miyaoka T, Yasukawa R, Yasuda H, Hayashida M, Inagaki T,

Horiguchi

J.

Department of Psychiatry, Shimane University School of Medicine,

89-1 Enyacho, Izumo 693-8501, Japan.

We present two cases of patients with schizophrenia treated with

minocycline. Minocycline (a second-generation tetracycline) is an

established and safe broad-spectrum antibiotic that crosses the

blood-brain barrier, with additional efficacy for diseases such as

acne

and rheumatoid arthritis. Animal studies have suggested that

minocycline

may prevent progression of some neurological disorders. Moreover, it

has

been reported that minocycline might have antidepressant effects. We

report two cases of acute schizophrenia with predominant catatonic

symptoms that responded to minocycline.

PMID: 17030375 [PubMed - in process]

2: Stroke. 2007 Jan;38(1):146-52. Epub 2006 Nov 22. Related

Articles, Links

Click here to read

Chronic treatment with minocycline preserves adult new neurons

and

reduces functional impairment after focal cerebral ischemia.

Liu Z, Fan Y, Won SJ, Neumann M, Hu D, Zhou L, Weinstein PR,

Liu J.

Department of Neurological Surgery, University of California-San

Francisco, San Francisco, CA 94121, USA.

BACKGROUND AND PURPOSE: Evidence suggests that activated

microglia

are detrimental to the survival of new hippocampal neurons, whereas

blocking inflammation has been shown to restore hippocampal

neurogenesis

after cranial irradiation and seizure. The aim of this current study

is

to determine the effect of minocycline on neurogenesis and functional

recovery after cerebral focal ischemia. METHODS: Four days after

temporary middle cerebral artery occlusion, minocycline was

administered

intraperitoneally for 4 weeks. BrdU was given on days 4 to 7 after

middle cerebral artery occlusion to track cell proliferation. The

number

of remaining new neurons and activated microglia were quantified in

the

dentate gyrus. Infarct volume was measured to assess the treatment

effect of minocycline. Motor and cognitive functions were evaluated 6

weeks after middle cerebral artery occlusion. RESULTS: Minocycline

delivered 4 days after middle cerebral artery occlusion for 4 weeks

did

not result in reduction in infarct size but significantly decreased

the

number of activated microglia in the dentate gyrus. Minocycline also

significantly increased the number of newborn neurons that

coexpressing

BrdU and NeuN without significantly affecting progenitor cell

proliferation in the dentate gyrus. Lastly, minocycline significantly

improved motor coordination on the rotor rod, reduced the

preferential

use of the unaffected limb during exploration, reduced the frequency

of

footfalls in the affected limb when traversing on a horizontal

ladder,

and improved spatial learning and memory in the water maze test.

CONCLUSIONS: Minocycline reduces functional impairment caused by

cerebral focal ischemia. The improved function is associated with

enhanced neurogenesis and reduced microglia activation in the dentate

gyrus and possibly improved neural environment after chronic

treatment

with minocycline.

Publication Types: * Research Support, N.I.H., Extramural

* Research Support, Non-U.S. Gov't

PMID: 17122429 [PubMed - in process]

3: Prog Neuropsychopharmacol Biol Psychiatry. 2006 Dec 30;30(8):1381-

93.

Epub 2006 Jul 12. Related Articles, Links

Click here to read

Protective effects of minocycline on behavioral changes and

neurotoxicity in mice after administration of methamphetamine.

Zhang L, Kitaichi K, Fujimoto Y, Nakayama H, Shimizu E, Iyo M,

Hashimoto K.

Division of Clinical Neuroscience, Chiba University Center for

Forensic Mental Health, 1-8-1 Inohana, Chiba 260-8670, Japan.

The effects of minocycline on behavioral changes and

neurotoxicity

in the dopaminergic neurons induced by the administration of

methamphetamine (METH) were studied. Pretreatment with minocycline

(40

mg/kg) was found to attenuate hyperlocomotion in mice after a single

administration of METH (3 mg/kg). The development of behavioral

sensitization after repeated administration of METH (3 mg/kg/day,

once

daily for 5 days) was significantly attenuated by pretreatment with

minocycline (40 mg/kg). A reduction in the level of dopamine (DA) and

its major metabolite, 3,4-dihydroxyphenyl acetic acid (DOPAC), in the

striatum after the repeated administration of METH (3 mg/kg x 3, 3-h

interval) was attenuated in a dose-dependent manner by pretreatment

with

and the subsequent administration of minocycline (10, 20, or 40

mg/kg).

Furthermore, minocycline (40 mg/kg) significantly attenuated a

reduction

in DA transporter (DAT)-immunoreactivity in the striatum after

repeated

administration of METH. In vivo microdialysis study demonstrated that

pretreatment with minocycline (40 mg/kg) significantly attenuated

increased extracellular DA levels in the striatum after the

administration of METH (3 mg/kg). In addition, minocycline was not

found

to alter the concentrations of METH in the plasma or the brain after

three injections of METH (3 mg/kg), suggesting that minocycline does

not

alter the pharmacokinetics of METH in mice. Interestingly, METH-

induced

neurotoxicity in the striatum was significantly attenuated by the

post-treatment and subsequent administration of minocycline (40

mg/kg).

These findings suggest that minocycline may be able to ameliorate

behavioral changes as well as neurotoxicity in dopaminergic terminals

after the administration of METH. Therefore, minocycline could be

considered as a useful drug for the treatment of several symptoms

associated with METH abuse in humans.

Publication Types:

* Research Support, Non-U.S. Gov't

PMID: 16839653 [PubMed - in process]

4: Exp Neurol. 2006 Dec 21; [Epub ahead of print] Related

Articles

Transient neuroprotection by minocycline following traumatic

brain

injury is associated with attenuated microglial activation but no

changes in cell apoptosis or neutrophil infiltration.

Bye N, Habgood MD, Callaway JK, Malakooti N, Potter A, Kossmann

T,

ti-Kossmann MC.

National Trauma Research Institute and Department of Trauma

Surgery,

Alfred Hospital, , Australia; Department of Medicine, Monash

University, , Australia.

Cerebral inflammation and apoptotic cell death are two processes

implicated in the progressive tissue damage that occurs following

traumatic brain injury (TBI), and strategies to inhibit one or both

of

these pathways are being investigated as potential therapies for TBI

patients. The tetracycline derivative minocycline was therapeutically

effective in various models of central nervous system injury and

disease, via mechanisms involving suppression of inflammation and

apoptosis. We therefore investigated the effect of minocycline in TBI

using a closed head injury model. Following TBI, mice were treated

with

minocycline or vehicle, and the effect on neurological outcome,

lesion

volume, inflammation and apoptosis was evaluated for up to 7 days.

Our

results show that while minocycline decreases lesion volume and

improves

neurological outcome at 1 day post-trauma, this response is not

maintained at 4 days. The early beneficial effect is likely not due

to

anti-apoptotic mechanisms, as the density of apoptotic cells is not

affected at either time-point. However, protection by minocycline is

associated with a selective anti-inflammatory response, in that

microglial activation and interleukin-1beta expression are reduced,

while neutrophil infiltration and expression of multiple cytokines

are

not affected. These findings demonstrate that further studies on

minocycline in TBI are necessary in order to consider it as a novel

therapy for brain-injured patients.

PMID: 17188268 [PubMed - as supplied by publisher]

5: Neuroscience. 2006 Sep 15;141(4):1835-48. Epub 2006 Jun 30.

Related Articles, Links

Click here to read

Combined minocycline plus pyruvate treatment enhances effects of

each agent to inhibit inflammation, oxidative damage, and neuronal

loss

in an excitotoxic animal model of Huntington's disease.

Ryu JK, Choi HB, McLarnon JG.

Department of Anesthesiology, Pharmacology and Therapeutics,

Faculty

of Medicine, 2176 Health Sciences Mall, The University of British

Columbia, Vancouver, BC, Canada V6T 1Z3.

The combination effects of minocycline (MC), a second-generation

tetracycline compound and pyruvate (PY), a glycolysis end metabolite

with antioxidant activity were investigated in the rat striatum

following an excitotoxic insult. Striatal injection of quinolinic

acid

(QUIN) resulted in marked inflammation characterized by microgliosis,

astrogliosis and enhanced expressions of pro-inflammatory enzymes

inducible nitric oxide synthase and cyclooxygenase-2. Inflammatory

responses were attenuated with administration of either MC or PY,

however, the combination of both compounds was significantly more

effective in reducing inflammation relative to MC or PY applied

alone.

Immunohistochemical analysis at 7 days post-intrastriatal QUIN

injection

showed extensive oxidative stress evident as lipid peroxidation,

oxidative DNA damage and reactive oxygen species formation which was

partially decreased by each agent applied separately but markedly

inhibited with the combination of the two compounds. In addition,

combination treatments significantly reduced neuronal loss in

QUIN-injected striatum compared with the agents applied separately.

Furthermore, long-term combination treatment decreased striatal

lesions

and inflammation after QUIN injection. These results demonstrate

that MC

and PY confer a considerably enhanced anti-inflammatory and

neuroprotective efficacy when applied together and suggest this

combinatorial procedure as a novel therapeutic strategy in

neurodegenerative disorders such as Huntington's disease which

exhibit

excitotoxic insults.

Publication Types:

* Comparative Study

* Research Support, Non-U.S. Gov't

PMID: 16809003 [PubMed - indexed for MEDLINE]

6: Life Sci. 2006 Jul 17;79(8):784-90. Epub 2006 Mar 2. Related

Articles, Links

Click here to read

Effects of second generation tetracyclines on

penicillin-epilepsy-induced hippocampal neuronal loss and motor

incoordination in rats.

Yilmaz I, Adiguzel E, Akdogan I, Kaya E, Hatip-Al-Khatib I.

Department of Pharmacology, Faculty of Medicine, Pamukkale

University, PO Box 33, Kinikli, 20070-Denizli, Turkey.

Epileptic seizures cause pathological changes such as sclerosis

and

pyramidal neuronal loss in the hippocampus. Experimentally, epilepsy

can

be induced by application of various chemicals directly to the

cerebral

cortex. In this study, epilepsy was induced in rats by intracortical

application of 500 IU penicillin G, and the effect of minocycline and

doxycycline on the resulting motor incoordination (rotarod) and

hippocampal neuronal loss in CA1, CA2 and CA3 fields (optical

fractionator method) were investigated. The rotarod performance was

reduced in the epilepsy group to 285.1+/-6.9 s (P<0.05 vs. sham-300

s).

Minocycline and doxycycline increased this performance to 297.4+/-

1.0 s

and 296.9+/-1.2 s respectively. No significant difference was

detected

between minocycline and doxycycline. The present results also showed

that the number of neurons (x10(3)) in the sham group was 150+/-9. In

the penicillin-epileptic rats, the number was decreased to 105+/-7

(P<0.01). Minocycline, but not doxycycline (125+/-8), significantly

increased the number to 131+/-3 (P<0.05). In conclusion, the second

generation tetracycline minocycline decreased the loss of hippocampal

neurons and motor incoordination in penicillin-epileptic rats.

Minocycline could protect against a variety of neurological insults

including epilepsy.

Publication Types:

* Research Support, Non-U.S. Gov't

PMID: 16554072 [PubMed - indexed for MEDLINE]

7: Eur J Neurosci. 2006 Jul;24(2):341-50. Epub 2006 Jul 12.

Related

Articles, Links

Click here to read

Minocycline attenuates hypoxia-ischemia-induced neurological

dysfunction and brain injury in the juvenile rat.

Fan LW, Lin S, Pang Y, PG, Cai Z.

Department of Pediatrics, Division of Newborn Medicine,

University

of Mississippi Medical Center, , 39216, USA.

To investigate whether minocycline provides long-lasting

protection

against neonatal hypoxia-ischemia-induced brain injury and

neurobehavioral deficits, minocycline was administered

intraperitoneally

in postnatal day 4 Sprague-Dawley rats subjected to bilateral carotid

artery occlusion followed by exposure to hypoxia (8% oxygen for 15

min).

Brain injury and myelination were examined on postnatal day 21 (P21)

and

tests for neurobehavioral toxicity were performed from P3 to P21.

Hypoxic-ischemic insults resulted in severe white matter injury,

enlarged ventricles, deficits in the hippocampus, reduction in

numbers

of mature oligodendrocytes and tyrosine hydroxylase-positive neurons,

damage to axons and dendrites, and impaired myelination, as

indicated by

the decrease in myelin basic protein immunostaining in the P21 rat

brain. Hypoxic-ischemic insult also significantly affected physical

development (body weight gain and eye opening) and neurobehavioral

performance, including sensorimotor and locomotor function, anxiety

and

cognitive ability in the P21 rat. Treatments with minocycline

significantly attenuated the hypoxia-ischemia-induced brain injury

and

improved neurobehavioral performance. The protection of minocycline

was

associated with its ability to reduce microglial activation. The

present

results show that minocycline has long-lasting protective effects in

the

neonatal rat brain in terms of both hypoxia-ischemia-induced brain

injury and the associated neurological dysfunction.

Publication Types:

* Research Support, N.I.H., Extramural

PMID: 16836639 [PubMed - indexed for MEDLINE]

8: Brain Res. 2006 Jun 6;1093(1):198-207. Epub 2006 May 18.

Related

Articles, Links

Click here to read

Behavioral and morphological effects of minocycline in the

6-hydroxydopamine rat model of Parkinson's disease.

Quintero EM, Willis L, Singleton R, N, Huang P, Bhat N,

Granholm AC.

Department of Neurosciences, Medical University of South

Carolina,

173 Avenue, Suite 403, ton, SC 29425, USA.

quintero@...

The neuropathology in many neurodegenerative diseases is

mediated by

inflammatory cascades that influence neuronal dysfunction and death.

Minocycline reduces the neurodegeneration observed in various models

of

Parkinson's. We exploited the unilateral 6-hydroxydopamine (6-OHDA)

lesion model to assess the effect of minocycline on related

neurodegeneration. Thirty Fisher 344 rats were divided into three

daily

treatment groups: (1) after: 45 mg/kg of minocycline beginning 24 h

after lesioning; (2) before: 45 mg/kg of minocycline beginning 3 days

before 6-OHDA lesioning; (3) control: corresponding saline-treated

controls. Animals were assessed for apomorphine-induced rotations

for 4

weeks. A longitudinal model for repeated measures showed that both

after

and before groups had significantly lower rotations than controls (P

<

0.001 for both comparisons). Pair-wise group comparisons showed that

the

before animals rotated less compared to controls (mean rotations: 164

+/- 38 versus 386 +/- 49, respectively, P = 0.001). After animals

also

rotated significantly less then controls (mean rotations: 125 +/- 41

versus 386 +/- 49, respectively, P < 0.001). Animals receiving

minocycline displayed reduced tyrosine hydroxylase-positive cell

loss in

the lesioned nigra versus contralateral nonlesioned nigra, compared

to

controls (mean differences: 5065 for after, 3550 for before, and 6483

for controls; P = 0.158 for after versus controls, P = 0.019 for

before

versus controls). The remaining lesioned nigral cells of both

minocycline-treated groups were larger than controls, with the most

robust cell size and fiber density observed in the after group. These

data suggest that the therapeutic potential of minocycline may

depend on

the time of drug administration relative to neuropathogenic event.

Publication Types:

* Research Support, Non-U.S. Gov't

PMID: 16712819 [PubMed - indexed for MEDLINE]

9: Glia. 2006 Jun;53(8):809-16. Related Articles, Links

Click here to read

Hypoxia-activated microglial mediators of neuronal survival are

differentially regulated by tetracyclines.

Lai AY, Todd KG.

Neurochemical Research Unit, Department of Psychiatry and

Centre for

Neuroscience, University of Alberta, Edmonton, Alberta, Canada.

The tetracycline derivatives minocycline (MINO) and doxycycline

(DOXY) have been shown to be neuroprotective in in vivo and in vitro

models of stroke. This neuroprotection is thought to be due to the

suppression of microglial activation. However, the specific molecular

parameters in microglia of the tetracyclines' effect are not

understood.

We subjected cultured rat microglial and neuronal cells to in vitro

hypoxia and examined the effects of MINO and DOXY pre-treatments. Our

data showed that MINO and DOXY protect against hypoxia-induced

neuronal

death by a mechanism dependent on regulation of microglial factors,

but

likely unrelated to regulation of microglial proliferation/viability.

Both MINO and DOXY suppressed the hypoxic activation of ED-1, a

marker

for microglial activation. Morphological analyses of hypoxic

microglia

using the microglial marker Iba1 revealed that treatment with MINO

and

DOXY caused a higher percentage of microglia to remain in a

non-activated state. MINO suppressed the hypoxic upregulation of

pro-inflammatory agents nitric oxide (NO), interleukin-1 beta

(IL-1beta), and tumor necrosis factor alpha (TNF-alpha), while DOXY

down-regulated only NO and IL-1beta. In contrast, the hypoxic

activation

of pro-survival/neuroprotective microglial proteins, such as

brain-derived neurotrophic factor (BDNF) and glial cell line-derived

neurotrophic factor (GDNF), were unaffected by tetracycline

treatments.

Taken together, these results suggest that MINO and DOXY may provide

neuroprotection against stroke by selectively down-regulating

microglial

toxic factors while maintaining functional pro-survival factors.

Publication Types:

* Research Support, Non-U.S. Gov't

PMID: 16541436 [PubMed - indexed for MEDLINE]

10: No To Shinkei. 2006 Jun;58(6):505-8. Related Articles, Links

[A case of brain nocardiosis successfully treated with

minocycline]

[Article in Japanese]

Suzuki C, Kimura T, Arai A, Maeda T, Tomiyama M, Kannari K,

Baba M,

Itabashi C, Wada R.

Department of Neurology, Hirosaki University School of

Medicine, 5

Zaifu-cho, Hirosaki 036-8562, Japan.

A 60-year-old man with surgically treated nocardia pyothorax was

referred to our hospital since he became drowsy. Brain MRI revealed

multiple brain abscesses. His cerebrospinal fluid (CSF) showed

increase

in polymorphonuclear cells and decrease in glucose. Since he was

allergic to sulfamethoxazole * trimethoprim, ceftriaxone and then

minocycline were given. Minocycline resulted in dramatic improvement

of

neurological symtoms, MRI findings and CSF cell count. PCR analysis

of

16S ribosomal DNA using his resected thoracic wall revealed that

nocardia from his tissue was strain IFM0860. Strain IFM0860 nocardia

was

found to be sensitive to minocycline but not to sulfamethoxazole *

trimethoprim and ceftriaxone. Intravenous administration of

minocycline

was followed by three-year per os administration of minocycline

during

which he had no recurrence of brain abscess. Thus, brain nocardiosis

could be successfully treated with appropriate antibiotics. The

lesson

from the present case is that identification of the type of nocardia

by

PCR analysis of 16S ribosomal DNA could help accomplish tailor-made

antibiotic therapy.

Publication Types:

* Case Reports

* English Abstract

PMID: 16856520 [PubMed - indexed for MEDLINE]

9: Med Pregl. 2000 May-Jun;53(5-6):266-71. Links

[Clinical use of tetracyclines in the treatment of periodontal

diseases]

[Article in Croatian]

* Bokor-Bratic M,

* Brkanic T.

Klinika za stomatologiju, Medicinski fakultet, Novi Sad, Hajduk

Veljkova.

INTRODUCTION: There are a number of chemically different

tetracycline homologues. The older group of tetracyclines, which was

introduced in the 1950-60s, includes tetracycline, oxytetracycline,

chlortetracycline and demeclocycline. The newer group of

tetracyclines

includes doxycycline, methacycline and minocycline. PHARMACOKINETICS:

Elevated concentration of tetracycline in gingival fluid with

respect to

blood levels was an unexpected phenomenon. Patients given 250 mg

every 6

hours had average crevicular fluid concentrations between 4 to 8 g/ml

and blood concentrations between 2 to 2.5 g/ml after 48 hours. The

levels in crevicular fluid and blood of volunteers who received 250

mg

every 12 hours were 2 to 4 g/ml and 0.3 to 1.4 g/ml respectively

after

48 hours. The concentration of doxycycline in gingival fluid after

administration of 200 mg/1st day and then 100 mg/day achieved average

level of 6 g/ml. Minocycline, a semisynthetic derivate of

tetracycline,

has shown to yield gingival fluid levels 5 times as high as serum

levels

after administration of 100 mg every 12 hours. MECHANISMS OF ACTION:

Tetracycline and its derivates demonstrate high in vitro activity

against most periodontal bacteria, including Actinobacillus

actinomycetemcomitans, Porphyromonas gingivalis, Prevotella

intermedia,

Eikenella corrodens, Wolinella recta and Fusobacterium nucleatum. The

study of in vitro susceptibility of these 6 bacterial strains showed

that, in regard to blood level, minimal inhibitory concentration is

higher and it is the concentration of the drug that can be expected

in

gingival fluid following oral administration of 100 mg per day

(doxycycline) (Table 1). The anti-inflammatory effect of

tetracyclines

was demonstrated histologically not only by reducing the size of the

infiltrated connective tissue, but qualitative changes were also

observed. Golub and associates have presented evidence that

tetracyclines inhibit collagenase activity in gingival fluid and in

tissue cultures. Therapeutic concentrations of tetracycline inhibit

chemotaxis, phagocytosis and random migration of neutrophils in

vitro.

ADVERSE EFFECTS: Great amounts of tetracyclines cause

gastrointestinal

disorders, nausea, vomiting and diarrhea. Tetracyclines suppress

activity of the enzymes in the bowel and pancreas. During longlasting

administration they can damage the liver and kidneys. Tetracyclines

can

cause photo-sensibilization. They make deposits with calcium in

bones,

specially during prenatal period and during growth, so they can cause

permanent teeth discoloration and hypoplasia. INTERACTIONS: The most

important interaction is with penicillin. These two kinds of

antibiotics

antagonize and decrease the therapeutic effect of each other, so

their

administration at the same time should be avoided. A significant

interaction occurs between tetracyclines and metal ions. This

interaction often has been observed in conjunction with use of

various

antacids. Tetracyclines can also influence the production and

absorption

of vitamin K. Nephrotoxicity has been reported when tetracyclines

have

been administrated in conjunction with methoxyflurane. INDICATIONS:

Doxycycline, due to its advantages over tetracycline (Table 2), is

indicated in treating destructive periodontal diseases including:

juvenile periodontitis and refractory marginal periodontitis.

Doxycycline therapy may be used for acute periodontal abscess and if

the

conditions are accompanied by general symptoms. Prophylactic

application

is recommended for implant placement procedures including membranes

in

guided tissue regeneration. RESULTS OF CLINICAL STUDY: ORAL

APPLICATION:

In spite of great number of published investigations this paper

presents

only the results of placebo-controlled, double-blind studies. There

is

evidence that therapy in localized juvenile periodontitis should

eliminate Actinobacillus actinomycetemcomitans, since 95% of patients

harbored this bacteria. (ABSTRACT TRUNCATED)

PMID: 11089368 [PubMed - indexed for MEDLINE]

--- End forwarded message ---