Retrospective analysis of 31 cases of nasopalatine duct cyst

OBJECTIVE: To perform a retrospective analysis of patients with nasopalatine duct cysts (NPDC) in Brazil and compare with previous analyses. MATERIALS AND METHODS: The files of the Laboratory of Oral Pathology (Minas Gerais Federal University) from 1966 to 1997 were reviewed. Demographic, clinical and histologic data of patients with nasopalatine duct cysts were collected. RESULTS: The mean age of patients with nasopalatine duct cysts at the time of diagnosis was 37.4 years and with a predilection for males. The majority of cases were asymptomatic. Histologically, non-keratinized stratified squamous epithelium alone or in combination with other epithelia was observed in 93% of the cases. Recurrence was not recorded. CONCLUSION: The demographic, histopathological, radiographic, and clinical data of the NPDC in our series are similar to previous studies in other populations.     

Recovery from Duret hemorrhage: a rare complication after craniotomy--case report

A 44-year-old female presented with Duret hemorrhage due to transtentorial herniation by extradural hematoma as a complication after craniotomy for treatment of spontaneous middle cranial fossa cerebrospinal fluid leakage through the oval window. Brain computed tomography revealed linear hemorrhage in the midbrain and the rostral pons. She awoke after 2 weeks in a coma, despite showing ocular bobbing and bilateral intranuclear ophthalmoplegia. She was discharged from the hospital with minimal neurological defects. Duret hemorrhage is usually fatal, but this case shows that early surgical decompression is the most important factor to avoid the worst sequelae.     

Comparison of the cytotoxicity of two nitroheterocyclic drugs (NHCD) towards transformed and non-transformed cells.

The cytotoxicity of two nitroheterocyclic compounds (NHCD), Nitracrine, 1-nitro-9(3'3'-dimethylaminopropylamino) acridine (Polfa, Poland) and Quinifuryl, 2-(5'-nitro-2'-furanyl) ethenyl-4-[N-[4-(N,N-diethylamino)-1'-methylbutyl] carbamoyl] quinoline (Dr. N. M. Sukhova, Institute of Organic Synthesis, Riga, Latvian Republic), towards two lines of leukaemic cells and a line of non-transformed cells, was determined under normoxia conditions. Although both drugs showed significant cytotoxicity to all cell lines (LC(50) for 24h, < or = 2 microM) with that of Nitracrine exceeding Quinifuryl, their toxicity towards murine leukaemia P388 was substantially higher, compared to murine fibroblasts NIH3T3. In addition, the rate of cell death was also two- to three-fold higher in case of P388 cells versus NIH3T3. Interestingly, human erythroleukaemia K562 cells were shown to uptake the drugs 10 min after their addition to the tissue culture medium, while the LC(50) values were reached after a substantial delay of 3h. This delay might be due to the intracellular transformation of drugs required for cell killing.     

Cyclosporin A induced internalization of the bile salt export pump in isolated rat hepatocyte couplets.

Isolated rat hepatocyte couplets were used to perform the comparative study of two widely used immunosuppressors, cyclosporin A (CsA) and tacrolimus (FK506) on hepatocanalicular function. We assessed canalicular function by counting the percentage of couplets that were able to accumulate the fluorescent cholephile, cholyl-lysyl-fluorescein (CLF), into the canalicular vacuole between the two cells, i.e., canalicular vacuole accumulation (CVA) of CLF. Compared to controls (DMSO-treated cells), CsA, in the approximate range of concentrations used therapeutically, caused inhibition of CVA of CLF, disorganization of the bile salt export pump (Bsep) localization at canalicular level resulting in its relocation into the cell, and disruption of the pericanalicular F-actin cytoskeleton. In contrast, FK506, at both approximately therapeutic and supratherapeutic concentrations, had no deleterious effect upon CVA of CLF, upon the localization of the bile salt transporter at the canalicular membrane, or on the organization of the pericanalicular F-actin cytoskeleton. These results point to transporter and cytoskeletal disorganization as contributors or determinants of CsA-induced cholestasis at canalicular level, whereas FK506 does not appear to produce these cholestasis-determining responses even at supratherapeutic concentrations.     

Efficacy of venlafaxine extended-release capsules in nondepressed outpatients with generalized anxiety disorder: A 6-month randomized controlled trial

CONTEXT: Generalized anxiety disorder (GAD) is a chronic disorder that is associated with debilitating psychic and somatic symptoms. Venlafaxine extended-release (XR) capsules have been shown to be effective in short-term treatment of patients with GAD without major depressive disorder (MDD), but long-term data are needed to establish whether this agent confers persistent benefits. OBJECTIVE: To compare the 6-month efficacy and safety of a flexible dosage of venlafaxine XR in outpatients with GAD without associated MDD. DESIGN: Six-month, randomized, double-blind, placebo-controlled, parallel-group trial conducted May 1996 to October 1997. SETTING: Fourteen outpatient clinics and private psychiatric practices in the United States. PARTICIPANTS: A total of 251 outpatients aged 18 years or older who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for GAD, had sufficient symptoms to require treatment, and did not have coexisting MDD. INTERVENTIONS: Participants were randomly assigned to receive either placebo (n=127) or venlafaxine XR (75, 150, or 225 mg/d, as required to control symptoms; n=124) for 28 weeks. MAIN OUTCOME MEASURES: Changes from baseline in the Hamilton Rating Scale for Anxiety (HAM-A) total score, the HAM-A psychic anxiety factor score, and the Clinical Global Impressions (CGI) scale Severity of Illness and Global Improvement scores, compared by intervention group. RESULTS: During weeks 6 through 28, response rates in the venlafaxine XR group were 69% or higher compared with rates of 42% to 46% in the placebo group (P<.001). By an evaluable-patient analysis, venlafaxine XR compared with placebo significantly improved anxiety scores from week 1 or 2 through week 28 on all primary efficacy measures, including the HAM-A total (P<.001), the HAM-A psychic anxiety factor (P<.001), and the CGI scale scores (P<.001). Adjusted mean changes from baseline to week 28 using last-observation-carried-forward methods were for HAM-A, venlafaxine XR -13.4, placebo -8.7 (P<.001); for HAM-A psychic anxiety score, venlafaxine XR -7.4, placebo -4.2 (P<.001); and for CGI-Improvement, venlafaxine XR 2.2, placebo 3.0 (P<.001). The most common treatment-emergent adverse event was nausea, followed by somnolence and dry mouth. CONCLUSIONS: This study is the first placebo-controlled demonstration of the long-term efficacy of any drug class in treating outpatients with DSM-IV-diagnosed GAD. Venlafaxine XR is an effective, rapidly acting, safe, once-daily agent for both the short- and long-term treatment of anxiety and may provide an important alternative to currently available anxiolytics. JAMA. 2000.     

Prevention of Mrp2 activity impairment in ethinylestradiol-induced cholestasis by ursodeoxycholate in the rat.

Ethinylestradiol (EE) induces cholestasis by affecting bile salt-dependent and -independent fractions of the bile flow. The decrease in bile salt-independent flow is thought to be due, in part, to a reduction in the expression of the canalicular transporter Mrp2. The impact of modulation of Mrp2 function by sodium ursodeoxycholate (UDC) in EE cholestasis is unknown. We evaluated the protective effect of UDC on EE-induced impairment of Mrp2 activity in vivo and in isolated hepatocytes, by using the substrate dinitrophenyl S-glutathione (DNP-SG). EE was administered to male Wistar rats at a dose of 5 mg/kg s.c. for 5 days. UDC was coadministered with EE at a dose of 25 mg/kg b.wt. i.p. for the same period. EE alone reduced DNP-SG biliary excretion by 55% when compared with controls. Coadministration with UDC partially restored the alteration. Secretion rate of DNP-SG was decreased by 30% in isolated hepatocytes from EE-treated rats, but, contrary to in vivo results, UDC coadministration did not restore DNP-SG transport, likely as a consequence of bile salt washout resulting from the isolation procedure. As a confirmation, tauroursodeoxycholate hepatocyte preloading significantly increased Mrp2 activity. Western blotting analysis of Mrp2 indicated that EE administration significantly reduced its level in total and plasma membranes and that UDC coadministration failed to revert this alteration. In conclusion, UDC improvement in Mrp2 transport activity in vivo likely derived from a direct enhancement of Mrp2 function rather than from a restoration of its expression levels. This provides a novel mechanism explaining the beneficial effects of UDC in EE-induced cholestasis.     

Mechanism of the endothelium-dependent vasodilator effect of an alcohol-free extract obtained from a vinifera grape skin.

An alcohol-free grape-skin extract (GSE) obtained from skins of Vitis labrusca has significant anti-hypertensive, antioxidant and vasodilator effects. According to our previous results, the vasodilator effect of GSE in the isolated mesenteric vascular bed (MVB) of the rat is dependent on endothelium and partially dependent on nitric oxide (NO). In the MVB of the rat pre-contracted with norepinephrine (NE), bolus injections of GSE induced a long-lasting dose-dependent vasodilation that is significantly reduced after the treatment with 1H-[1,2,3] oxadiazolo [4,4-a] quinoxalin-1-one (ODQ). Additionally, in vessels pre-contracted with norepinephrine and depolarized with KCl (25 mM) or treated with Ca(2+)-dependent K(+)-channel blockers charybdotoxin (ChTx) plus apamin, the vasodilator effect of GSE was significantly reduced and almost abolished by ChTx plus apamin plus L-NAME. However, the vasodilator effect of GSE was unaffected by D-Arg[Hyp(3),Thi(5),D-Tic(7),Oic(8)]bradykinin (HOE-140), atropine, yohimbine, pyrilamine and 4-aminopyridine (4-AP). The vasoconstriction response elicited by bolus injection of KCl was not affected by GSE, whereas the vasoconstrictor response induced by NE was dose-dependently and completed inhibited by GSE in the presence but not in the absence of endothelium. However, NE-induced vasoconstriction in calcium-free condition or without endothelium was not reduced by GSE. The present results demonstrate that GSE induces a vasodilator effect in the rat MVB, which is dependent on NO in combination with endothelium-derived hyperpolarizing factor (EDHF). Additionally, our results indicated that extracellular Ca(2+) has an important role on the endothelium-dependent vasodilator effect induced by GSE.     

Signaling modulation of bile salt-induced necrosis in isolated rat hepatocytes.

Hydrophobic bile salts induce either necrosis or apoptosis depending on the severity of the injury caused by them. Since bile salt-induced apoptosis is influenced by Ca2+- and protein kinase-signaling pathways, and both necrosis and apoptosis share common initiating mechanisms, we analyzed whether these signaling cascades also influence bile salt-induced necrosis in isolated rat hepatocytes. Taurochenodeoxycholate (TCDC, 0.25-1.50 mM, 2 h) reduced, in a dose-dependent manner, the percentage of viable hepatocytes, and increased the release of the cytosolic enzyme, lactate dehydrogenase (LDH) and alanine aminotransferase (ALAT), and that of the plasma membrane enzyme, alkaline phosphatase (AP). The PKC inhibitors, H7 (100 microM) and chelerythrine (2.5 microM), both prevented significantly TCDC-induced necrosis. On the contrary, the PKA activator, dibutyryl-cAMP, exacerbated TCDC-induced cell damage in a dose-dependent manner; this effect was more likely due to cAMP-mediated PKA activation, as the PKA inhibitor, KT5720 (1 microM), counteracted this effect. Instead, the intracellular Ca2+ chelator, BAPTA/AM (20 microM), was without effect. TCDC (1 mM) increased lipid peroxidation from 0.7 +/- 0.2 to 7.5 +/- 0.9 nmol of malondialdehyde per mg of protein, p < 0.001; the addition of the free radical scavenger, diphenyl-p-phenylendiamine, completely blocked this increase and prevented significantly TCDC-induced necrosis. PKC inhibition induced only a slight attenuation of TCDC-induced lipid peroxidation. Possible mechanisms accounting for the modulatory effect of signal transduction pathways on TCDC-induced necrosis, including signaling influence on TCDC transport events and TCDC-induced oxidative stress, are discussed.