Main alkaloids from the Brazilian dendrobatidae frog Epipedobates flavopictus: pumiliotoxin 251D, histrionicotoxin and decahydroquinolines.

Epipedobates flavopictus, Dendrobatidae, is a small aposematic frog found in Brazilian Cerrado bioma. In the present work, we isolated and characterized chemically the most abundant alkaloids present in the cutaneous extract of E. flavopictus. The specimens were collected in Pirenópolis (Goiás, Brazil), their skins were removed and extracted with methanol, and submitted to purification by HPLC and identification by gas chromatography and mass spectrometry. Pumiliotoxin 251D, histrionicotoxin 285Da and two decahydroquinolines, 219A and 243A, were identified. The pumiliotoxin 251D was tested on isolated frog sciatic nerve and on isolated guinea pig ileum muscle. The pumiliotoxin 251D slightly reduced the action potentials amplitude of frog sciatic nerve. The crude skin extract of E. flavopictus and the pumiliotoxin 251D produced rhythmic contractions and increased the muscular tension on isolated guinea pig ileum.     

Oral leiomyosarcomas: report of two cases with immunohistochemical profile.

Leiomyosarcoma of the oral cavity is a very rare tumor associated with aggressive clinical behavior and low survival. In this paper, we report 2 cases of leiomyosarcoma, affecting the gingival mucosa of a 54-year-old female and the maxillary bone of a 63-year-old male. Histologically, the tumors were composed of variably oriented fascicles of spindle-shaped cells with cigar-shaped nuclei and eosinophilic cytoplasm. The lesions were treated by surgical resection. Immunoreactivity to anti-vimentin, anti-smooth muscle actin, anti-desmin, anti-laminin, and anti-muscle-specific actin antibodies were found; conversely, the tumor cells were negative for anti-S100 and AE1/AE3 proteins. This report emphasizes the role of immunohistochemical study for correct diagnosis of leiomyosarcoma.     

Cyclooxygenase-2 inhibition increases gastric tone and delays gastric emptying in rats.

We evaluated the effects of cyclooxygenase-2 (COX-2) selective inhibitors, COX-1 selective inhibitor, or COX non-selective inhibitor on gastric emptying and intestinal transit of liquids, and evaluated the effect of a COX-2 selective inhibitor on gastric tonus (GT). Male Wistar rats were treated per os with saline (control), rofecoxib, celecoxib, ketorolac, rofecoxib + ketorolac, celecoxib + ketorolac, or indomethacin. After 1 h, rats were gavage-fed (1.5 mL) with the test meal (5% glucose solution with 0.05 g mL(-1) phenol red) and killed 10, 20 or 30 min later. Gastric, proximal, medial or distal small intestine dye recovery (GDR and IDR, respectively) were measured by spectrophotometry. The animals of the other group were treated with i.v. valdecoxib or saline, and GT was continuously observed for 120 min using a pletismomether system. Compared with the control group, treatment with COX-2 inhibitors, alone or with ketocolac, as well as with indomethacin increased GDR (P < 0.05) at 10-, 20- or 30-min postprandial intervals. Ketorolac alone did not change the GDR, but increased the proximal IDR (P < 0.05) at 10 min, and decreased medial IDR (P < 0.05) at 10 and 20 min. Valdecoxib increased (P < 0.01) GT 60, 80 and 100 min after administration. In conclusion, COX-2 inhibition delayed the gastric emptying of liquids and increased GT in rats.     

18F-FDG PET/CT delayed images after diuretic for restaging invasive bladder cancer.

PET with (18)F-FDG has been considered of limited value for detection of bladder cancer because of the urinary excretion of the tracer. The purpose of this study was to investigate the role of PET/CT in the detection and restaging of bladder cancer using furosemide and oral hydration to remove the excreted (18)F-FDG from the bladder. METHODS: Seventeen patients with bladder cancer (11 without cystectomy, 6 with total cystectomy and urinary diversion) underwent (18)F-FDG PET/CT from head to the upper thighs 60 min after the intravenous injection of 370 MBq of (18)F-FDG. Additional pelvic images were acquired 1 h after the intravenous injection of furosemide and oral hydration. PET/CT findings were confirmed by MRI, cystoscopy, or biopsy. RESULTS: PET/CT was able to detect bladder lesions in 6 of 11 patients who had not undergone cystectomy. These images changed the PET/CT final reading in 7 patients: Recurrent bladder lesions were detected in 6 patients, pelvic lymph node metastases in 2 patients, and prostate metastasis in 1. This technique overcame the difficulties posed by the urinary excretion of (18)F-FDG. Hypermetabolic lesions could be easily detected by PET and precisely localized in the bladder wall, pelvic lymph nodes, or prostate by CT. Seven of 17 patients (41%) were upstaged only after delayed pelvic images. CONCLUSION: Detection of locally recurrent or residual bladder tumors can be dramatically improved using (18)F-FDG PET/CT with delayed images after a diuretic and oral hydration.     

Agomelatine and its therapeutic potential in the depressed patient

Despite advances in understanding potential disease mechanisms and in developing novel therapeutic approaches to the treatment of major depressive disorder, the disease continues to carry an enormous personal, social, and economic burden. Agomelatine represents an important opportunity to advance the treatment of depression. It is a melatonergic (MT₁ and MT₂) agonist and serotonergic (5HT_2C) antagonist. Evidence from animal models of depression, complements emerging clinical data. In a dose range of 25–50 mg daily, agomelatine is an effective antidepressant with a very favorable side-effect profile. In particular, sleep restorative action in the absence of sedation and minimal effect on sexual function suggests that agomelatine represents a worthwhile treatment alternative for patients with major depressive disorder.     

Protection Against Chemically-Induced Oxidative Gastrointestinal Tissue Injury in Rats by Bismuth Salts

Oxygen free radicals (OFR) are implicated in thepathogenesis of stress, chemically induced gastriclesions, and gastrointestinal injury. Theconcentration-dependent scavenging abilities of bismuthsubsalicylate (SBS), colloidal bismuth subcitrate (CBS), andselected OFR scavengers, including superoxide dismutase(SOD), catalase, mannitol, and allopurinol were examinedagainst biochemically or chemically generated superoxide anion, hydroxyl radical, andhypochlorite radical plus hypochlorous acid based on achemiluminescence assay. Furthermore, both gastric (GM)and intestinal mucosa (IM) were individually exposed in vitro to these free radical generatingsystems, and the concentration-dependent protectiveabilities of SBS and CBS against lipid peroxidation (LP)were compared with selected OFR scavengers. In addition, 24-hr fasted rats were orally treated with thenecrotizing agents 0.6 M HCl, 0.2 M NaOH, 80% ethanol,and aspirin (200 mg/kg). The extent of tissue injury inthe GM and IM was determined by assessing LP, DNA fragmentation, and membrane microviscosity.Dose- and time-dependent in vivo protective abilities ofCBS (100 mg/kg) and SBS (15 mg/kg) were also assessed.Following incubations with superoxide anion and hydroxyl radical generating systems in thepresence of 125 mg SBS/liter, approximately 47% and 61%inhibitions were observed in the chemiluminescenceresponse, respectively, while 48% and 46% inhibitions were observed with 125 mg CBS/liter. SBS andCBS exerted similar abilities towards hypochloriteradical plus hypochlorous acid. Approx. 3.1- and3.7-fold increases in LP were observed in the GM and IMof rats following oral administration of 0.6 MHCl. Pretreatment of the rats with SBS and CBS decreased0.6 M HCl-induced LP in the GM by approx. 39% and 27%,respectively, with similar decreases in LP in the IM. SBS exhibited better protectiveabilities towards 0.6 M HCl and 0.2 m NaOH-induced GMand IM injury as compared to CBS. SBS and CBS providedsimilar protection towards 80% ethanol-induced gastric injury, while CBS exerted a superior protectiveability towards aspirin-induced gastric injury. Theresults demonstrate that both SBS and CBS can scavengereactive oxygen species and prevent tissue damage produced by OFR.     

In vitro and in vivo effects of clindamycin on polymorphonuclear leukocyte function.

The effects of clindamycin on polymorphonuclear leukocytes (PMNLs) were evaluated in vitro and in vivo in an experimental model and in immunocompromised patients with and without infection. Chemotaxis, chemiluminescence, and bactericidal capacity were evaluated using PMNLs preincubated with clindamycin in different concentrations. In the three phases of the study, clindamycin at a concentration of 2 mg/L significantly increased PMNL function. In contrast, when higher concentrations were used, PMNL function was not modified and in some cases it was decreased. Our findings suggest that clindamycin, in concentrations of 2 mg/L, positively modifies PMNL function.     

The midterm (6 years) clinical results of the Carpenter-Edwards supra-annular bioprosthesis]

We present here the clinical results with a second-generation porcine bioprosthesis, the Carpentier-Edwards supra-annular valve (CESA). Two-hundred and twenty-two CESA bioprostheses were implanted in 189 patients during a four-year period (from 1984 to 1987), either as an isolated procedure or associated to mitral or tricuspid repair. The mid-term clinical results have been evaluated after a mean follow-up of 3.4 years, being 96% complete. There were 16 in-hospital deaths (8.4%) and 6 late, potentially valve-related, cardiac deaths (1.1% patients/year). Overall, 86.7 +/- 2% of the patients were free from cardiac death at 6 years (95.1 +/- 2% of the patients surviving the operative period). Linearized rates of valve related complications were the following: 1.4% patients/year for thromboembolism (including valve thrombosis), 0.5% patients/year for treatment-related hemorrhage and 0.7% patients/year for endocarditis. We did not found any case of either intrinsic or extrinsic valve failure, unrelated to infection of thrombosis. Two patients were reoperated, one because of valve thrombosis and the other due to prosthetic valve endocarditis (reoperation rate of 0.3% patients/year). When lethal and nonlethal valve-related complications (including in-hospital deaths) were considered all together, 75.8 +/- 8.4% of the patients remained alive and free of morbid events at 6 years. When patients were grouped according to the valve replaced (aortic, mitral and multiple), best results were found with patients submitted to isolated aortic valve replacement. We conclude that the CESA bioprosthesis has an excellent mid-term clinical performance. However, longer follow-up is necessary to know if improvement in valve design and manufacturing results in increased valve durability.