Intracellular signalling in the ovine pars tuberalis: an investigation using aluminium fluoride and melatonin.

The effect of aluminium fluoride (AlF4-) has been studied on inositol phosphate accumulation, calcium mobilization, cyclic AMP production and [2-125I]iodomelatonin binding in ovine pars tuberalis cells. These cells have high-affinity receptors for, and respond to, melatonin through inhibition of forskolin-stimulated adenylate cyclase. In the presence of 10 mM LiCl, AlF4- stimulated the net accumulation of inositol monophosphate and inositol bisphosphate. Consistent with these findings, AlF4- increased intracellular calcium; although this response was attenuated in calcium-depleted medium, indicating that the calcium response comprises both intracellular and extracellular components. Melatonin was ineffective on either basal or AlF4(-)-stimulated turnover of inositol phosphates. In concordance with the inositol phosphate response, melatonin had no effect on either the AlF4(-)-stimulated or the basal calcium levels. AlF4- blocked the increase in cyclic AMP stimulation by 1 microM forskolin, being as effective as melatonin, achieving approximately 90% inhibition. AlF4- also attenuated the binding of [2-125I]iodomelatonin to ovine pars tuberalis membranes by 15%. At the concentration used, these results are consistent with the interpretation that AlF4- activates many G protein-mediated responses, and thus imply that the inhibitory pathway for cyclic AMP predominates over the stimulatory arm, whereas there can only be a stimulatory pathway linked to phosphoinositide metabolism in ovine pars tuberalis cells.     

The use of locally-delivered doxycycline in the treatment of periodontitis. Clinical results*

Abstract. The clinical safety and effectiveness of a subgingivally-delivered biodegradable drug delivery system containing doxycycline hyclate (DH) has been evaluated in 3 large 9-month multicenter randomized parallel-design controlled clinical trials. A total of 1002 patients having at least 2 quadrants with a minimum of 4 qualifying pockets ≥5 mm that bled on probing were enrolled. Each subject had ≥7 mm probing depths in 2 of the qualifying pockets. Study 1 (n= 180) compared DH to sanguinarine chloride (SC) and vehicle control (VC). Study 2 (n=411) and study 3 (n=411) compared DH to VC, scaling and root planing (SRP), and oral hygiene (OH). Clinical measurements included probing depth reduction (PDR), attachment level gain (ALG), bleeding on probing reduction (BOP) and plaque index (PI). Analysis of efficacy data from these 3 trials show all treatments gave significant positive clinical changes from baseline at most time points. Study 1 results indicate that DH was superior to SC and VC in PDR at all time points. Similar results were obtained for ALG when DH was compared to SC and VC, For BOP reductions, DH was superior to VC al all time points and to SC at months 5 through 9. For DH, mean ALG in deep (≥7 mm) pockets was 1.4 mm; mean PDR for DH was 2.6 mm. For moderate (5 to 6 mm) pockets, ALG was 0.8 mm and PDR 1.5 mm. Studies 2 and 3 reported mean month 9 ALG for SRP as 0.7 mm and 0.8 mm, respectively. For DH, ALG was 0.8 mm in both studies 2 and 3. At month 9 in studies 2 and 3, 29%, and 31%, of DH sites and 27% and 34% of SRP sites showed ALG ≥2 mm. Probing depth reductions followed the same pattern, with 32% of DH sites and 32% of SRP sites showing ≥2 mm PD reductions in study 2, and 41% of DH and 43% of SRP sites showing PDR of ≥2 mm in study 3. Comparisons between DH, VC, and OH treatment groups in studies 2 and 3 showed DH treatment was statistically superior to VC and OH at most time points. Results of these 3 large clinical trials demonstrate that treatment of periodontitis with 10% doxycyline hyclate in a bioabsorbable delivery system is equally as effective as SRP and superior in effect to VC and OH in reducing the clinical signs of adult periodontitis.     

Adhesions between muscle and bone after forearm fracture mimicking mild Volkmann's ischemic contracture.

Five cases of digital flexion contractures after healed forearm fractures were incorrectly diagnosed as mild Volkmann ischemic contractures. All failed to respond to conservative therapy and were considered significant enough to require surgical correction. At surgery, the involved muscle-tendon units were densely adherent to the bone and callus of the fracture site with no evidence of ischemic involvement of the muscle. Lysis of adhesions and lengthening of the contracted muscle corrected the deformities.     

Subcortical arteriosclerotic encephalopathy: brain stem findings with MR imaging

Magnetic resonance images of 44 patients who had varying degrees of supratentorial signal abnormalities compatible with subcortical arteriosclerotic encephalopathy (SAE) were reviewed for posterior fossa findings. Brain stem lesions frequently accompanied supratentorial SAE and were seen as multiple, fairly symmetric areas of poorly defined, increased signal intensity on axial T2-weighted images. Involvement was generally confined to the central portions of the mid and upper pons. The typical appearance of brain stem involvement by SAE and its probable pathogenesis are reviewed.     

Disruption of circadian coordination accelerates malignant growth in mice

An animal model (mice B6D2F1) was developed to study the consequence of suprachiasmatic nuclei (SCN) destruction on tumor growth. SCN destruction abolished the rest-activity and body temperature rhythms and markedly altered the rhythms in serum corticosterone concentration and lymphocyte count. Tumor growth was faster in mice with lesioned SCN than in controls for both tumor models studied, Glasgow osteosarcoma (GOS) and pancreatic adenocarcinoma (P03). This shows that disruption of circadian coordination accelerates malignant growth in mice, suggesting that the host circadian clock controls tumor progression.