Preoperative versus postoperative radiation therapy for soft-tissue sarcomas

In this article, we report results from a retrospective consecutive series of 117 patients with soft-tissue sarcomas treated with adjuvant radiation and surgical resection at 2 associated institutions. Fifty-nine patients received preoperative radiation; 58 patients received postoperative radiation. Mean clinical follow-ups were 6.1 years and 8.4 years, respectively. Nineteen (32.2%) of 59 patients in the preoperative group and 17 (29.3%) of 58 patients in the postoperative group had wound complications (P = .89). Three (5.1%) of 59 sarcomas in the preoperative group and 7 (12.1%) of 58 sarcomas in the postoperative group recurred locally (P = .19). Improved local disease control and other potential advantages of using preoperative radiation make this a preferred adjuvant treatment.     

The effects of intratendinous and retrocalcaneal intrabursal injections of corticosteroid on the biomechanical properties of rabbit Achilles tendons

BACKGROUND: The use of corticosteroid injections in the treatment of retrocalcaneal bursitis is controversial. We assessed the effects of corticosteroid injections, both within the tendon substance and into the retrocalcaneal bursa, on the biomechanical properties of rabbit Achilles tendons. The systemic effects of bilateral corticosteroid injections were also studied. METHODS: The rabbits were divided into three treatment groups. The rabbits in Group I received injections of corticosteroid into the Achilles tendon on the left side and injections of normal saline solution into the Achilles tendon on the right, those in Group II received injections of corticosteroid into the retrocalcaneal bursa on the left side and injections of saline solution into the Achilles tendon on the right, and those in Group III received injections of corticosteroid into the Achilles tendon on the left side and injections of corticosteroid into the retrocalcaneal bursa on the right. These injections were given weekly for three weeks. At four weeks after the final injection, the tendons were harvested and were tested biomechanically to determine failure load, midsubstance strain and total strain, modulus of elasticity, failure stress, and total energy absorbed. The site of failure was also documented. The groups were compared according to the location of the injections, the type of injection (steroid or saline solution), and the total systemic load of steroid. RESULTS: Specimens from limbs that had received intratendinous injections of corticosteroid showed significantly decreased failure stress compared with those from limbs that had received intratendinous injections of saline solution (p = 0.008). Specimens from limbs that had received intrabursal injections of corticosteroid demonstrated significantly decreased failure stress (p = 0.05), significantly decreased total energy absorbed (p = 0.017), and significantly increased total strain (p = 0.049) compared with specimens from limbs that had received intratendinous injections of saline solution. Specimens from limbs that had received intratendinous injections of corticosteroid were biomechanically equivalent to specimens from limbs that had received intrabursal injections of corticosteroid. Specimens from rabbits that had received bilateral injections of corticosteroid demonstrated significantly decreased failure load (p = 0.011), modulus of elasticity (p = 0.015), failure stress (p = 0.03), and total energy absorbed (p = 0.015) compared with those from rabbits that had received unilateral injections of steroid. CONCLUSIONS: Local injections of corticosteroid, both within the tendon substance and into the retrocalcaneal bursa, adversely affected the biomechanical properties of rabbit Achilles tendons. Additionally, tendons from rabbits that had received bilateral injections of corticosteroid demonstrated an additive adverse effect, with significantly worse biomechanical properties compared with tendons from rabbits that had received unilateral injections of corticosteroid.     

Biochemical and morphological evaluation of ischemia-reperfusion injury in rat small bowel modulated by ischemic preconditioning

The objective of this study was to evaluate the effect of ischemic preconditioning upon lesions produced by ischemia-reperfusion of the small intestine. Thirty EPM-1 Wistar rats were randomly distributed into three groups: ischemic preconditioning (IPC; n = 12), ischemia-reperfusion (I/R; n = 12), and control (C; n = 6). Laparotomy permitted isolation of the mesenteric artery for clamping. The animals were heparinized and hydrated. IPC was induced by: 10 minutes of ischemia followed by 10 minutes of reperfusion and then 50 minutes ischemia followed by another 30 minutes reperfusion. Group I/R was submitted to the same protocol except for the 20 minutes of preconditioning. Group C animals underwent only laparotomy for 100 minutes. After reperfusion small intestine fragments were examined histologically. Blood samples were obtained to measure LDH and lactate prior to euthanasia. Lactate values were significantly lower in the IPC as compared to I/R group, 39 versus 67 mg/dL, respectively (P < or =.05). However, neither IPC (grade 3) lesions of the mucosa versus I/R (grade 4) nor LDH values (PCI = 680, I/R = 873 U/L) were statistically different. Thus No morphological evidence of protection was observed following ischemic preconditioning.     

Feeding induced by increasing doses of neuropeptide Y: dual effect on hypothalamic serotonin release in normal rats

Endogenous neuropeptide Y (NPY) levels increase during fasting and before dark onset in rats. The feeding that follows these states elicits the release of serotonin in the lateral hypothalamus (LH), as part of the physiological mechanisms controlling satiety. With the hypothesis that exogenous NPY-induced feeding should also stimulate serotonin, we measured its release in the LH of non-fasted rats, which received a single intracerebroventricular injection of either 1.0, 2.0, or 5.0 microg of NPY. After 1.0 microg, the cumulative 2-h intake was of 13 g and serotonin release significantly increased (54% peak). These feeding and serotonergic responses were highly similar to the ones we observed in a previous study, in which feeding followed an overnight fast. Thus, the 1.0 microg NPY dose stimulated intake while preserving the normal serotonergic activation. Contrarily, as the NPY dose was increased to either 2.0 or 5.0 microg, the cumulative 2-h intakes were of 18 g, but the serotonergic stimulation was absent. It is suggested that this dual NPY effect relies on a finely tuned control mechanism, reflecting the existence of a narrow range of NPY levels within which the serotonergic stimulation resembles those seen in physiological states.     

Evidence for the involvement of vanilloid receptor in the antinociception produced by the dialdeydes unsaturated sesquiterpenes polygodial and drimanial in rats

This study investigated whether or not the neonatal treatment of rats with the sesquiterpenes polygodial or drimanial could cause persistent antinociception similar to that induced by capsaicin. Rats were injected subcutaneously 48 h after birth with capsaicin (50 mg/kg), polygodial (150 mg/kg), drimanial (150 mg/kg) or vehicle (1ml/kg). Six to eight weeks later, rats were tested in models of nociception. Treatment of rats with capsaicin, polygodial or drimanial produced significant inhibition of the first phase and, to a lesser extent, the second phase of formalin-induced nociception. A significant reduction in Complete Freund's Adjuvant and capsaicin-induced hyperalgesia was observed in the animals neonatally treated with capsaicin, polygodial or drimanial compared with vehicle-treated rats. Moreover, both sesquiterpenes caused inhibition of plasma extravasation induced by injection of capsaicin. The neonatal treatment with capsaicin, polygodial or drimanial significantly decreased [3H]-resiniferatoxin binding sites in the rat spinal cord, but only capsaicin neonatal treatment significantly reduced the expression of TRPV1 in dorsal root ganglia (DRG) when assessed by Western blot. These results extend our previous findings demonstrating that the neonatal treatment of rats with polygodial or drimanial, similar to that reported for capsaicin, produced persistent antinociception in adult animals associated with TRPV1 down-regulation in the spinal cord, but not TRPV1 expression in DRG.     

Anthropometry and body composition in ethnic Japanese and Caucasian adolescent girls: considerations on ethnicity and menarche

OBJECTIVE: This study aimed to compare the various anthropometric and body composition parameters based on the ethnicity and the absence or presence of menarche. DESIGN: A cross-sectional study with incomplete sampling, using the subject as the evaluation unit. SUBJECTS: The final sample of 550 subjects was composed of 122 Japanese and 179 Caucasian premenarcheal adolescents, and 72 Japanese and 177 Caucasian postmenarcheal adolescents. METHODS: The variables of body composition were measured through the following methods: bioelectrical impedance analysis, near-infrared interactance (NIR), Slaughter cutaneous skinfold equations and body mass index. Weight, height and sitting height were also evaluated. RESULTS: The Japanese pre- and postmenarcheal girls presented lower weight and height values when compared with the Caucasian girls. In general, the Japanese premenarcheal girls presented less fat and fat-free mass than the premenarcheal Caucasian girls. This fact was demonstrated through NIR results. Conversely, the Japanese postmenarcheal adolescents accumulated more fat than their Caucasian counterparts. However, significant differences were solely encountered in the values of cutaneous skinfold percent body fat. With regard to menarche, it was verified that, regardless of ethnicity, all the anthropometric and body composition variables reached higher values among postmenarcheal adolescents when compared with premenarcheal adolescents. CONCLUSION: Different results of weight and height between the ethnic groups may bring back the discussion concerning separate growth curves for different ethnic groups. The results of the body composition analysis indicated high adiposity levels among postmenarcheal adolescents.     

Polycationic peptides as inhibitors of mast cell serine proteases

When mast cells are activated, e.g. during allergic responses, they secrete the serine proteases chymase and tryptase, which both are complex-bound to heparin proteoglycan in vivo. Previous reports have demonstrated potent pro-inflammatory effects of both tryptase and chymase in different animal models, suggesting that these serine proteases may be relevant targets for therapeutic intervention. Recent investigations have shown that heparin-binding compounds can cause tryptase inhibition and it has been suggested that the inhibitory activity of such compounds is due to interference with the binding of heparin to tryptase. Here we tested various polycationic peptides for their ability to inhibit heparin-free human recombinant betaI-tryptase. We demonstrate powerful direct inhibition of tryptase (IC(50) values approximately 1-100 nM) by poly-Arg and poly-Lys of different molecular weights. Poly-Arg and poly-Lys showed predominantly competitive inhibition kinetics, although decreases in the k(cat) values for the chromogenic substrate S-2288 were also observed. Peptides built up from heparin-binding motifs were also inhibitors of tryptase, albeit of lower efficiency than poly-Arg/Lys. Tryptase inhibition was strongly dependent on the size of the polycationic peptides. The various polycationic peptides were also inhibitory for heparin-dependent activities of chymase. The tryptase inhibition caused by the polycationic peptides could be reversed by adding heparin. After heparin-induced rescue of tryptase activity, the major part of the tryptase activity was sensitive to inhibition by bovine pancreatic trypsin inhibitor, whereas tryptase before addition of polycationic peptide was completely resistant. Taken together, our findings indicate that polycationic peptides can be used as powerful agents for combined inhibition of mast cell tryptase and chymase.