Different pharmacological characteristics in L6 and C2C12 muscle cells and intact rat skeletal muscle for amylin, CGRP and calcitonin.

1. We compared the ability of rat amylin, rat calcitonin gene-related peptide (CGRP) and rat and salmon calcitonins to elevate cyclic AMP levels and to inhibit [U-14C]-glucose incorporation into glycogen in insulin-stimulated intact rat soleus muscle and in two cell lines derived from rodent skeletal muscle, L6 and C2C12. 2. In intact soleus muscle, both amylin (EC50S of 0.7-6.1 nM) and salmon calcitonin (EC50S of 0.5-1.4 nM) were more potent than CGRP (EC50S of 5.6-15.8 nM) and were much more potent than rat calcitonin (EC50S of 50-137 nM) at stimulating cyclic AMP production, activating glycogen phosphorylase and inhibiting insulin-stimulated [14C]-glycogen formation. 3. In contrast, in both L6 and C2C12 cells, CGRP (EC50S of 0.042-0.12 nM) stimulated cyclic AMP formation and inhibited insulin-stimulated [U-14C]-glucose incorporation into glycogen approximately 1000 times more potently than amylin (EC50S 34-240 nM), while salmon calcitonin was without measurable effect. 4. There was a correlation between elevation of cyclic AMP and inhibition of insulin-stimulated [U-14C]-glucose incorporation into glycogen evoked by these peptides in both intact muscle (r2 = 0.69, P < 0.0004) and muscle cell lines (r2 = 0.96, P < 0.0001). 5. In conclusion, the effects of amylin, CGRP, and calcitonin on soleus muscle glycogen metabolism appear to be mediated by adenylyl cyclase-coupled receptors which show a pharmacological profile similar to high affinity amylin binding sites that have been previously reported in rat brain. In contrast, the effects of amylin and CGRP in L6 and C2C12 rodent muscle cell lines appear to be mediated by adenylyl cyclase-coupled receptors that behave like CGRP receptors.     

Minor complications after mandibular third molar surgery: type, incidence, and possible prevention.

PURPOSE: The aim of this prospective study was to ascertain the incidence of minor complications after mandibular third molar surgery and to predict the risk of skin ecchymosis or mucosa petechiae related to the usage of an absorbable gelatin sponge. PATIENTS AND METHODS: One hundred and four patients subjected to surgical extraction of horizontally impacted lower third molars were selected and investigated by means of questionnaires and clinical examinations. The independent sample t test was used for numeric variables. The chi-square test was used for logistic variables to determine the association between variables, and thereafter stepwise logistical regression was used. RESULTS: The older group (> or = 30 years old), with deeply impacted teeth, and long operation times (> or = 10 minutes) were shown to have significantly higher swelling than the other groups (P < .05). The patients who had deeply impacted teeth or long operation times were shown to have significantly higher VAS scores compared to short operation times (P < .05). The use of an absorbable gelatin sponge in the extraction socket significantly decreased postoperative swelling, mucosal petechiae, and skin ecchymosis (P < .05). CONCLUSION: The clinical variables related to postoperative bleeding disorder, pain, and trismus were identified. The insertion of an absorbable gelatin sponge into the extraction socket was found to be a very useful method to prevent postoperative bleeding problems.     

Paired kidney analysis of tacrolimus and cyclosporine microemulsion-based therapy in Chinese cadaveric renal transplant recipients

Few studies used paired kidneys for comparison between tacrolimus and cyclosporine in renal transplantation. Most of the published data used whole blood trough levels for drug monitoring. However, the use of limited sampling strategy and abbreviated formula to estimate the 12-h area under concentration-time curve (AUC(0-12)) allowed better prediction of drug exposure. Sixty-six first cadaveric renal transplant recipients receiving paired kidneys were randomized to receive either tacrolimus-based (n = 33) or cyclosporine microemulsion (Neoral)-based therapies (n = 33). Abbreviated AUC(0-12) was used for drug monitoring and dose titration. Mean follow-up duration was 2.8 +/- 2 years. The patient and graft survival were comparable. Fewer incidence of acute rejection was observed in tacrolimus group (15% vs. 27.3%) though the difference was not significant (P = 0.23). The absolute value and the rate of decline of creatinine clearance were both significantly better in tacrolimus-treated patients. Prevalence of hypertension, post-transplant diabetes mellitus, infection, and malignancy were similar in both groups. Prevalence of hypercholesterolemia (11/33 vs. 4/33) and gum hypertrophy (6/33 vs. 1/33) was more common in cyclosporine-treated patients (P = 0.04 in both parameters). This was the first prospective, randomized study with paired kidney analysis showing the renal function was significantly better in tacrolimus-treated patients than in cyclosporine-treated patients.     

Management of congenital tracheal stenosis

Objectives: Congenital tracheal stenosis is a rare disease. Various methods for treatment exist but there is still much debate as to the appropriate surgical procedure. We present our surgical experiences of patch tracheoplasty and slide tracheoplasty as viable methods for the treatment of congenital tracheal stenosis. Methods: From 1994 to 2002, 13 patients were diagnosed with congenital tracheal stenosis. Eight patients (7 symptomatic and 1 asymptomatic) had their stenosis corrected, three by means of pericardial patch tracheoplasty, four by slide tracheoplasty, and one by resection and anastomosis. Concomitant operations were performed on six patients to treat congenital cardiovascular disease. Five patients showing no significant symptoms did not undergo tracheal surgery and received only cardiac procedures. A retrospective review of the hospital course, complications, and long-term results was conducted. Results: Among the patch tracheoplasty group, every patient suffered from granulation tissue formation. One patient died of respiratory acidosis and one was hospitalized due to recurrent granulation tissue, which required frequent bronchoscopy. The third patient from this group is free of all symptoms. Among the slide tracheoplasty group, one patient died of anastomosis disruption. The three remaining patients are alive and well. The one patient who received resection and anastomosis is alive without symptoms. Conclusions: Surgical repair of long-segment congenital tracheal stenosis exhibited high mortality and morbidity rates. Every patient that underwent pericardial patch tracheoplasty suffered from troublesome granulation tissue. As slide tracheoplasty provided relatively good results in the short and mid-term follow-up periods, it seems to be a preferred method for the treatment of long-segment congenital tracheal stenosis.     

Estrogen receptor alpha pathway is involved in the regulation of Calbindin-D9k in the uterus of immature rats.

It has been demonstrated in our previous studies that Calbindin-D9k (CaBP-9k) is a potent biomarker for screening estrogen-like chemicals in the rat model. Although treatments with 17beta-estradiol (E2) and endocrine disrupting compounds resulted in the up-regulation of uterine CaBP-9k, the mechanism of CaBP-9k induction by these compounds through two subtypes of estrogen receptors (ERalpha and ERbeta) is unclear. Thus, in the present study, immature rats were treated with propyl pyrazole triol (PPT, an ERalpha-selective ligand), diarylpropionitrile (DPN, an ERbeta-selective ligand), E2, or dimethyl sulfoxide (DMSO, a vehicle control) for three days in order to clarify which subtype of ER is involved in the uterine CaBP-9k induction. Following injection with these ER ligands, uterine CaBP-9k expression was analyzed by Northern blot and immunoblot assays. Uterine CaBP-9k expression is mainly mediated by PPT in a dose- and time-dependent manner in immature rats, whereas no significant alteration of the uterine CaBP-9k gene was observed after DPN treatment. In addition, an estrogenicity of PPT in inducing CaBP-9k expression was completely blocked by the anti-estrogen ICI 182,780, implying that uterine CaBP-9k is solely induced by ERalpha. A single treatment with PPT rapidly increased the protein levels of ERalpha and PR, an E2-mediated gene, in these tissues. Taken together, these results indicate that uterine CaBP-9k is induced by E2 and endocrine disrupting chemicals via the ERalpha pathway, but not ERbeta, in the uterus of immature rats.     

Pharmacological evidence, using in vivo dialysis, that substances additional to ascorbic acid, uric acid and homovanillic acid contribute to the voltammetric signals obtained in unrestrained rats from chronically implanted carbon paste electrodes

In vivo voltammetry at chronically implanted carbon paste electrodes in unrestrained rats is a particularly useful technique for evaluating neurochemical changes during spontaneous behaviour, or behaviour under experimental control. A 3 peak signal is observed in the striatum; most recently the consensus view has attributed these peaks to ascorbic acid (AA), uric acid (UA) and homovanillic acid (HVA) in ascending order of oxidation potential. We have used a pharmacological approach, combined with in vivo dialysis, to further elucidate the nature of the contributing species. Allopurinol, an inhibitor of xanthine oxidase, and thus of uric acid production, has previously been reported to abolish peak 2. We now report, using dialysis, that it selectively depletes UA in the extracellular fluid (ECF). Pargyline, a monoamine oxidase inhibitor, reduces peak 3 transiently (max. 60%) as expected, however it results in a more sustained reduction in ECF HVA (max. 100%). It also increases peak 1 (max. 75%) and decreases peak 2 (max. 40%), although changes in ECF AA and UA measured by dialysis and HPLC are minimal. Pargyline does however reduce ECF 5-hydroxyindoleacetic acid by 65%. We conclude that, using linear sweep voltammetry at chronically implanted paste electrodes: (a) one or more substances in addition to AA can contribute to peak 1; dopamine can do so in some situations; (b) 5-hydroxyindoleacetic acid, as well as UA, contributes to peak 2; its contribution is about one third that of the latter; and (c) one or more substances in addition to HVA can contribute to peak 3. 3-Methoxytyramine can do so. Since this is another methylated metabolite of dopamine, this does not prevent the use of peak 3 as an index of dopamine metabolism, and may extend its usefulness to situations where monoamine oxidase is inhibited.