RESUMO
Objective: Compare the perioperative outcomes and disease-free survival between minimally invasive and open surgery in women with stage I-II high-risk endometrial cancer. Methods: A retrospective, cohort study was performed involving twenty-four centers from Argentina. Patients with grade 3 endometrioid, serous, clear cell, undifferentiated carcinoma or carcinosarcoma who underwent hysterectomy, bilateral salpingo-oophorectomy, and staging between January 2010-2018 were included. Cox hazard regression analysis and Kaplan-Meier curves evaluated the association of surgical technique with survival. Results: Of 343 eligible patients, 214 (62 %) underwent open surgery and 129 (38 %) underwent laparoscopic surgery. No significant differences were seen between the two groups with respect to greater or equal grade III Clavien-Dindo postoperative complications (11 % in the open surgery group vs 9 % minimally invasive surgery group; P = 0.34) Minimally invasive surgery was not associated with worse disease-free survival at four years (79.14 % [95 % CI 69.42- 86.08] vs 78.80 % [95 % CI 70.61-84.96]), (p = 0.25), even after creating a Cox proportional model (hazard ratio [HR] 1.08 95 % CI 0.63-1.84); (p = 0.76). Conclusion: There was no difference between postoperative complications nor oncologic outcomes comparing minimally invasive and open surgery among patients with high-risk endometrial cancer.
RESUMO
New chiral (S,E)-γ-N,N-dibenzylated nitroalkenes 2a-c were synthesized from natural L-(α)-amino acids in five steps with overall yields of 68-88%. The conjugate addition of hydride, methoxide, nitronate and azide nucleophiles to 2a-c led to the corresponding chiral 1,3-nitroamines in 74-90% yield. The conjugate addition of cyanide anion to 2a,b was followed by HNO2 elimination affording chiral aminated acrylonitriles (73-98%). On the other hand, the azide anion reacted with 2a, in acetonitrile, via a [3 + 2]-cycloaddition in which HNO2 was lost, providing the corresponding 1,2,3-triazole derivative. Direct reduction of 1,3-nitroamine derivatives 9a,b produced the corresponding 1,3-diamines in good yields.
RESUMO
The compound (±)-trans-4-hydroxy-6-propyl-1-oxocyclohexan-2-one [(±)-δ-lactone] was isolated from the plant Vitex cymosa Bertero, and determined to be the active principle. The present study aimed to evaluate the antinociceptive effect of (±)-δ-lactone and to elucidate its mechanism of action. Mice were subjected to in-vivo models of acute pain (acetic acid-induced abdominal writhing, formalin and hot-plate tests) and the open-field test. (±)-δ-Lactone, administered orally (6-900 µmol/kg), exerted a dose-dependent antinociceptive effect in the acetic acid-induced abdominal writhing, formalin and hot-plate tests. (±)-δ-Lactone administered by the intrathecal (i.t.) and subplantar (s.p.) routes (10-600 nmol) exerted concentration-dependent antinociceptive effects in the formalin test, showing its spinal and peripheral activity, respectively. In the hot-plate test, (±)-δ-lactone was also active when administered i.t., confirming its spinal effect. The previous intraperitoneal (i.p.) application of naloxone, yohimbine, mecamylamine or glibenclamide did not alter the effect produced by the i.t. administration of (±)-δ-lactone, whereas the previous application of atropine and L-arginine significantly reduced its effects in the formalin and hot-plate tests. The previous i.p. application of L-NAME enhanced the antinociceptive effect of the i.t. administration of (±)-δ-lactone in the formalin and hot-plate tests. The previous i.p. application of L-NAME and L-arginine increased and decreased, respectively, the activity of (±)-δ-lactone administered by s.p. administration. These results indicate that (±)-δ-lactone has significant spinal and peripheral antinociceptive activity, and that its effects are at least partially mediated by a reduced nitric oxide production/release, most likely through mechanisms involving the cholinergic system.
Assuntos
Dor Aguda/prevenção & controle , Analgésicos não Narcóticos/uso terapêutico , Neurônios Colinérgicos/efeitos dos fármacos , Lactonas/uso terapêutico , Óxido Nítrico/antagonistas & inibidores , Nervos Periféricos/efeitos dos fármacos , Nervos Espinhais/efeitos dos fármacos , Dor Aguda/metabolismo , Administração Oral , Analgésicos não Narcóticos/administração & dosagem , Analgésicos não Narcóticos/efeitos adversos , Analgésicos não Narcóticos/antagonistas & inibidores , Animais , Comportamento Animal/efeitos dos fármacos , Brasil , Neurônios Colinérgicos/metabolismo , Relação Dose-Resposta a Droga , Etnofarmacologia , Comportamento Exploratório/efeitos dos fármacos , Injeções Espinhais , Injeções Subcutâneas , Lactonas/administração & dosagem , Lactonas/efeitos adversos , Lactonas/antagonistas & inibidores , Masculino , Camundongos , Óxido Nítrico/metabolismo , Medição da Dor/efeitos dos fármacos , Nervos Periféricos/metabolismo , Nervos Espinhais/metabolismo , Vitex/químicaRESUMO
The diastereoselective synthesis of (+/-)-trans-4-hydroxy-6-propyl-1-oxocyclohexan-2-one, as a mixture trans:cis (3:1), was accomplished using a protocol that combine the Prins cyclization and RuO(4) oxidation. The synthesis this lactone allowed the elucidation of the correct structure of the substance isolated from the barks of Vitex cymosa. The delta-lactones mixture showed significant antinociceptive properties in preliminary tests using the tail flick model assay.
Assuntos
Analgésicos/química , Analgésicos/uso terapêutico , Lactonas/química , Lactonas/uso terapêutico , Dor/tratamento farmacológico , Vitex/química , Analgésicos/síntese química , Animais , Ciclização , Lactonas/síntese química , Estrutura Molecular , EstereoisomerismoRESUMO
Eleven species of fleas were collected from 601 small rodents, from November 1995 to October 1997, in areas of natural focus of bubonic plague, including the municipalities of Nova Friburgo, Sumidouro and Teresópolis, State of Rio de Janeiro, Brazil. Among 924 fleas collected, Polygenis (Polygenis) rimatus (Rhopalopsyllidae) was the predominant species regarding the frequency, representing 41.3 percent (N:382), followed by P. (Neopolygenis) pradoi, representing 20 percent (N:185) and Craneopsylla minervaminerva (Stephanocircidae), representing 18.9 percent (N:175). The host Akodon cursor harbored 47.9 percent of these fleas. Other six host species were infested by 52.1 percent of the remaining fleas. Fleas were found on hosts and in places within the focus not previously reported by the literature