Lubricin in synovial fluid of mild and severe temporomandibular joint internal derangements.

BACKGROUND: To understand the molecular basis of temporomandibular joint (TMJ) pathologies, we aimed to investigate the lubricin levels in the TMJ synovial fluid (SF) of patients with mild to severe internal derangements (IDs). MATERIAL AND METHODS: A total, 34 joints were the study group. Only patients, with a Wilkes stage of III, IV and V were included, in this sample. Control group consisted of SF from eight joints, from patients undergoing to orthognatic surgery. Concentrations of lubricin in the SF from both samples were measured using ELISA system. RESULTS: The mean lubricin concentration was 7.029 ± 0.21 µg/mL in stage III patients; 5.64 ± 0.10 µg/mL in stage IV patients, and 4.78 ± 0.11 µg/mL in stage V patients. The lubricin levels from stage IV and stage V patients differed significantly (P ≤ 0.001) from those of control subjects. Lubricin levels were inversely correlated with age and to VAS score. CONCLUSIONS: The results of this cross-sectional study highlight the relationship between disease severity and the levels of lubricin in TMJ SF. Our findings suggest that novel biotherapeutic approaches, including the administration of recombinant lubricin in the joint cavity, for the treatment of TMJ diseases can be developed.

Effects of oral contraceptives on the prevalence of alveolar osteitis after mandibular third molar surgery: a retrospective study.

The objective of this study was to investigate the influence of oral contraceptives on the incidence rate of alveolar osteitis (AO) following the surgical extraction of both impacted mandibular third molars. This retrospective study reviewed the clinical records of patients who presented to the oral surgery clinic of a university school of dentistry for the extraction of impacted mandibular third molars. Using a database search, all patients were categorized by sex, age, occurrence of AO, and whether the females were taking oral contraceptives at the time of surgery. The patient was considered positive for AO if either one or both sockets developed AO. The incidence of AO among women taking oral contraceptives at the time of impacted mandibular third molar extraction differed significantly from that in the other patient groups. AO occurred in 37.9% (11/29) of females taking oral contraceptives, while only 8.9% (16/179) of females who were not taking oral contraceptives at the time of extraction developed AO. The total incidence of AO among females was 13.0% (27/208). The total incidence of AO among the 363 males and females presenting for mandibular third molar extractions was 13.8%. Females who are taking oral contraceptives at the time of impacted mandibular third molar extraction are at a higher risk of developing AO following extraction.

Histological and immunohistochemical evaluation of biphasic calcium phosphate and a mineral trioxide aggregate for bone healing in rat calvaria.

This work focused on the process of bone repair of defects in standardized calvaria of Wistar rats treated with biphasic calcium phosphate (BCP), mineral trioxide aggregate (MTA), or a combination of the two. Eighty Wistar rats were divided into four treatment groups and were examined at 2 and 8 weeks. A surgical defect was created in the calvaria using a 6-mm diameter trephine drill. The cavity was treated with BCP, MTA, or BCP+MTA; untreated rats with clot formation served as controls. Samples were evaluated histologically and by immunohistochemical staining for areas of new osteoid tissue and new bone tissue, as well as the percentage of labelled cells using anti-bone morphogenetic protein receptor type 1B (anti-BMPR1B) antibodies. Statistically significant differences were found for all dependent variables (area of new osteoid tissue, area of new bone, and percentage immunostaining) by group (P<0.0001) and time (P<0.0001), and for the interaction of the two (P<0.0001). The MTA group at 8 weeks showed the highest amount of osteoid tissue. The same group also exhibited the highest amount of bone tissue formation. The 2-week MTA samples and 2-week BCP+MTA samples exhibited the highest percentages of stained cells. The best results in terms of the area of osteoid and bone tissue formation and the percentage of BMPR1B were observed for the MTA group, confirming that the combination of BCP+MTA does not result in a significant improvement.

TRAIL, DR5 and caspase 3-dependent apoptosis in vessels of diseased human temporomandibular joint disc. An immunohistochemical study.

To evaluate the apoptosis involvement in the angiogenesis as a self-limiting process in patients with temporomandibular joint (TMJ) degenerated disc vessels, we assessed, by immunohistochemistry, the detection of TRAIL, its death receptor DR5 and caspase 3. TRAIL, its death receptor DR5 and caspase 3 expression were studied by immunohistochemistry in 15 TMJ discs displaced without reduction and in 4 unaffected discs. These apoptosis molecules were detected in the intima and media layers of newly formed vessels affected discs. In conclusion, vessels apoptosis activation in TMJ disc with ID could be regarded as a self-limiting process that try to leads to vessel regression; in this way an inhibition of angiogenic vessels may prove a key strategy in limiting pathological angiogenesis, by cutting off blood supply to tumors, or by reducing harmful inflammation.

Traumatic neuroma following sagittal split osteotomy of the mandible.

A 16-year-old male underwent bilateral sagittal split osteotomy of the mandible to correct a mandibular deficiency. Twenty-one years later, a routine panoramic radiograph revealed a radiolucent lesion on the left side of the mandible. The lesion was biopsied. As the patient did not have symptoms and the lesion was connected to the inferior alveolar nerve, the lesion was not totally excised in order to preserve nerve function. The histological features were consistent with traumatic neuroma, and no further surgical procedure was planned.

Nicotine at concentrations found in cigarette smokers activates and desensitizes nicotinic acetylcholine receptors in CA1 interneurons of rat hippocampus.

Behavioral effects of cigarette smoking are attributed to the interactions of nicotine with brain nicotinic acetylcholine receptors (nAChRs). However, the mechanisms by which nAChR function in developing and mature brain is affected by a smoker's level of nicotine (50-500 nM) remain unclear. Thus, the objective of this study was to determine the concentration- and time-dependent effects of nicotine on alpha7 and alpha4beta2 nAChRs, the two major brain subtypes, natively expressed in CA1 interneurons of rat hippocampal slices. Only at concentrations > or =5 microM did nicotine (applied for 6-60 s) elicit action potentials or measurable whole-cell currents (EC(50)=158 microM) in stratum radiatum interneurons that express alpha7 nAChRs. Continuous exposure for 10-15 min of the neurons to nicotine (0.5-2.5 microM) inhibited alpha7 nAChR-mediated currents (IC(50)=640 nM) evoked by choline (10 mM). Nicotine (> or =0.125 microM) applied to the neurons for 1-5 min induced slowly desensitizing whole-cell currents (EC(50)=3.2 microM) in stratum lacunosum moleculare interneurons; this effect was mediated by alpha4beta2 nAChRs. Also via activation of alpha4beta2 nAChRs, nicotine (0.125-0.5 microM) increased the frequency and amplitude of GABAergic postsynaptic currents (PSCs) in stratum radiatum interneurons. However, exposure of the neurons for 10-15 min to nicotine (0.25-0.5 microM) resulted in desensitization of alpha4beta2 nAChRs. It is suggested that nanomolar concentrations of nicotine after acute intake suppress inhibitory inputs to pyramidal cells through a disinhibitory mechanism involving activation of alpha4beta2 nAChRs and desensitization of alpha7 nAChRs, and after chronic intake leads to up-regulation of both receptor subtypes via desensitization. These findings have direct implications to the actions of nicotine in cigarette smokers.

The opioid antagonist naltrexone inhibits activity and alters expression of alpha7 and alpha4beta2 nicotinic receptors in hippocampal neurons: implications for smoking cessation programs.

This study was designed to investigate whether naltrexone, an opioid antagonist that has been evaluated clinically as a co-adjuvant in smoking cessation programs, affects function and expression of neuronal nicotinic receptors (nAChRs). Whole-cell current recordings from rat hippocampal neurons in culture and in slices demonstrated that alpha7 nAChRs can be inhibited non-competitively by naltrexone (IC(50) approximately 25 microM). The voltage dependence of the effect suggested that naltrexone acts as an open-channel blocker of alpha7 nAChRs. Naltrexone also inhibited activation of alpha4beta2 nAChRs in hippocampal neurons; however its IC(50) was higher ( approximately 141 microM). At a concentration as high as 300 microM (which is sufficient to block by 100% and 70% the activity of alpha7 and alpha4beta2 nAChRs, respectively), naltrexone had no effect on kainate and AMPA receptors, blocked by no more than 20% the activity of NMDA and glycine receptors, and reduced by 35% the activity of GABA(A) receptors. A 3-day exposure of cultured hippocampal neurons to naltrexone (30 microM) or nicotine (10 microM, a concentration that fully desensitized alpha7 nAChRs) resulted in a 2-fold increase in the average amplitude of alpha7 nAChR-subserved currents. Naltrexone did not augment the maximal up-regulation of alpha7 nAChRs induced by nicotine, indicating that both drugs act via a common mechanism. In addition to increasing alpha7 nAChRs-mediated responses per neuron, nicotine increased the number of neurons expressing functional non-alpha7 nAChRs (probably alpha4beta2 nAChRs); this effect was blocked by naltrexone (0.3 and 30 microM). Therefore, naltrexone may affect dependence on cigarette smoking by differentially altering function and expression of alpha7 and alpha4beta2 nAChRs in the central nervous system.

Binding of dipyridamole to phospholipid vesicles: a fluorescence study.

Binding and localization of the vasodilator and antitumor drug coactivator dipyridamole (DIP) and one of its derivatives, RA25, to phospholipid vesicles of DMPC (dimyristoylphosphatidylcholine) and DPPC (dipalmitoylphosphatidylcholine) was studied using fluorescence spectroscopy as well as quenching of fluorescence. The analysis of fluorescence data indicates that neutral dipyridamole binds to the phospholipids in their liquid crystalline phase with an association constant of 950 M(-1) and 1150 M(-1) to DMPC and DPPC, respectively. Protonation of DIP leads to a 3-fold reduction of the association constant. For the gel phospholipid phase, the binding is smaller (a factor of 2), independently of pH, suggesting that the more flexible lipid packing in the liquid crystalline phase facilitates the binding of the drug. The association constant of RA25 neutral form is considerably lower than for DIP, being around 295 M(-1). Fluorescence quenching with nitroxides TEMPO and stearic acid doxyl derivatives suggests the localization of DIP to be closer to the 5th carbon of alkyl chain. The quenching effect of 5-DSA below the lipid phase transition suggests that a strong static quenching may be operative. The quenching effect of 16-DSA is almost as great as that for 5-DSA below the phase transition, being even higher above the phase transition. This effect is probably due to the trans-gauche isomerization of the stearic acid nitroxide, making the encounter of its paramagnetic fragment with the DIP chromophore possible. Our data are consistent with DIP location close to the bilayer surface in the border of hydrophobic-polar heads interface which is similar to the data in micellar systems. In the case of RA25, the drug is in the outer part of the head group interface being much exposed to the aqueous phase and being significantly less accessible to the membrane nitroxide quenchers.