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Experimental topical tetracycline-induced neuritis in the rat*1
John C. Leist DMD, MS, Major, formerly, Chief Resident, currently, Chief*, 1, 3, John R. Zuniga DMD,
PhD, Associate Professor, †, , Ning Chen MD, Formerly, Visiting Research Fellow, currently,
Associate Professor‡, 3 and Steve Gollehon, Senior Dental Student§
* USAF, DC, USA
1 Department of Oral and Maxil ofacial Surgery, University of North Carolina at Chapel Hil , Chapel Hil ,
NC, USA3 Department of Oral and Maxil ofacial Surgery, Misawa AFB, Japan.
† Department of Oral and Maxil ofacial Surgery, University of North Carolina at Chapel Hil , Chapel Hil ,
NC., USA‡ Department of Oral and Maxil ofacial Surgery, University of North Carolina at Chapel Hil , Chapel Hil ,
NC, USA3 Department of Oral Maxil ofacial Surgery, Nanjing Medical University, Nanjing, People's Republic of
§ School of Dentistry, University of North Carolina at Chapel Hil , Chapel Hil , NC., USA
Recent studies have reported that tetracycline may induce chronic inflammatory responses
in the adjacent soft tissues. The purpose of the present study was to determine if dry, powdered
tetracycline evoked an inflammatory response in nerve tissue.
Twenty male Sprague-Dawley rats were anesthetized and bilateral mental
nerves were exposed. Half of the 40 nerves were intentionally injured by removing the epineurium, and
the remaining nerves were uninjured. In a prospective, randomized, double-blind manner, equal volumes
of color-matched, precoded tetracycline powder or Gelfoam (Upjohn, Kalamazoo, MI) powder control was
placed in intimate contact with the nerves and sealed in polyethylene tubes. Forty-five days later the
animals were kil ed and 5-µm sections of the nerves were prepared for histologic examination. The
presence of epineurium, fascicular number, and fascicular area were measured. An inflammatory
response in nerve tissue and the intrafascicular and epifascicular inflammatory index was measured by
counting darkly stained nuclei with a Jandel Video Analysis System (Jandel Scientific, Corte Madera,
Experimental injury (ie, epineurectomy) of nerves resulted in a statistically significant
increase in fascicular number (P
= .034), but not in fascicular area. For the intrafascicular inflammatory
index, there was a significant main effect for drug (P
= .002) and injury (P
= .002). Experimental injury in
both Gelfoam control and tetracycline grouped nerves resulted in an increase in intrafascicular
inflammation. There was no significant increase in intrafascicular inflammation in either Gelfoam control
or tetracycline grouped nerves when the epineurium was intact. The combination of both tetracycline
and epineurectomy resulted in the largest increase in intrafascicular inflammation found among the
groups studied. For epifascicular inflammatory index, there was a significant main effect for drug (P
.003) and injury (P
= .001) that mirrored the intrafascicular inflammatory pattern.
The results of the present study suggest that dry, powdered tetracycline accentuates
the inflammatory response in intrafascicular and epifascicular nerve tissue fol owing epineurectomy. The
maintenance of epineurium inhibited the inflammatory response in intrafascicular and epifascicular nerve
tissues. Gelfoam was an inert material when placed against exposed nerve tissue. These findings
suggest that tetracycline should not be placed in extraction sockets when injury of the inferior alveolar
Corresponding author. Address correspondence and reprint requests to Dr Zuniga: Department of
Oral and Maxillofacial Surgery, School of Dentistry, CB#7450, Chapel Hill, NC 27599-7450.
*1 This study was supported in part by United States Air Force and National Institute of Dental
Anti-Inflammatory Living By Rachel Abrams, M.D. You probably don’t spend much time thinking about inflammation in your body, but inflammation is a buzz-word in the medical community these days is because it is such an important part of health and wellness. We generally think of inflammation as painful redness or swelling around injuries or joints, but the process of inflammation is used throu
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