Amifostine reduces inflammation and protects against 5-fluorouracil-induced oral mucositis and hyposalivation.

Oral mucositis (OM) is a common and dose-limiting side effect of cancer treatment, including 5-fluorouracil (5-FU) and radiotherapy. The efficacy of the therapeutic measures to prevent OM is limited and disease prevention is not fully observable. Amifostine is a cytoprotective agent with a described anti-inflammatory potential. It is clinically used to reduce radiotherapy and chemotherapy-associated xerostomia. This study investigated the protective effect of amifostine on an experimental model of OM. Hamsters were divided into six groups: saline control group (5 mL/kg), mechanical trauma (scratches) of the right cheek pouch; 5-FU (60 and 40 mg/kg, ip, respectively, administered on days 1 and 2); amifostine (12.5, 25, or 50 mg/kg) + 5-FU + scratches. Salivation rate was assessed and the animals were euthanized on day 10 for the analysis of macroscopic and microscopic injury by scores. Tissue samples were harvested for the measurement of neutrophil infiltration and detection of inflammatory markers by ELISA and immunohistochemistry. 5-FU induced pronounced hyposalivation, which was prevented by amifostine (P<0.05). In addition, 5-FU injection caused pronounced tissue injury accompanied by increased neutrophil accumulation, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1ß) tissue levels, and positive immunostaining for TNF-α, IL-1ß, and inducible nitric oxide synthase (iNOS). Interestingly, amifostine prevented the inflammatory reaction and consequently improved macroscopic and microscopic damage (P<0.05 vs 5-FU group). Amifostine reduced inflammation and protected against 5-FU-associated oral mucositis and hyposalivation.

Amifostine reduces inflammation and protects against 5-fluorouracil-induced oral mucositis and hyposalivation

Oral mucositis (OM) is a common and dose-limiting side effect of cancer treatment, including 5-fluorouracil (5-FU) and radiotherapy. The efficacy of the therapeutic measures to prevent OM is limited and disease prevention is not fully observable. Amifostine is a cytoprotective agent with a described anti-inflammatory potential. It is clinically used to reduce radiotherapy and chemotherapy-associated xerostomia. This study investigated the protective effect of amifostine on an experimental model of OM. Hamsters were divided into six groups: saline control group (5 mL/kg), mechanical trauma (scratches) of the right cheek pouch; 5-FU (60 and 40 mg/kg, ip, respectively, administered on days 1 and 2); amifostine (12.5, 25, or 50 mg/kg) + 5-FU + scratches. Salivation rate was assessed and the animals were euthanized on day 10 for the analysis of macroscopic and microscopic injury by scores. Tissue samples were harvested for the measurement of neutrophil infiltration and detection of inflammatory markers by ELISA and immunohistochemistry. 5-FU induced pronounced hyposalivation, which was prevented by amifostine (P<0.05). In addition, 5-FU injection caused pronounced tissue injury accompanied by increased neutrophil accumulation, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) tissue levels, and positive immunostaining for TNF-α, IL-1β, and inducible nitric oxide synthase (iNOS). Interestingly, amifostine prevented the inflammatory reaction and consequently improved macroscopic and microscopic damage (P<0.05 vs 5-FU group). Amifostine reduced inflammation and protected against 5-FU-associated oral mucositis and hyposalivation.

Organometallic gold(iii) complexes with hybrid SNS-donating thiosemicarbazone ligands: cytotoxicity and anti-Trypanosoma cruzi activity.

Stable organogold(iii) compounds of the composition [AuIII(Hdamp)(L1)]Cl are formed from reactions of [AuCl2(damp)] with H2L1 (damp- = dimethylaminomethylphenyl; H2L1 = N'-(diethylcarbamothioyl)benzimidothiosemicarbazides). The cationic complexes can be neutralized by reactions with weak bases under the formation of [AuIII(damp)(L1)] compounds. The structures of the products show interesting features like relatively short AuH contacts between the methylene protons of the Hdamp ligand and the gold(iii) ions. Preliminary biological studies on the uncoordinated compounds H2L1 and their gold complexes indicate considerable cytotoxicity for the [AuIII(Hdamp)(L1)]Cl complexes against MCF-7 cells. The in vitro trypanocidal activity was evaluated against the intracellular form of Trypanosoma cruzi. The organometallic complexes display a remarkable activity, which is dependent on the alkyl substituents of the thiosemicarbazone building blocks of the ligands. One representative of the cationic [AuIII(Hdamp)(L1)]Cl complexes, where H2L1 contains a dimethylthiosemicarbazide building block, shows a trypanocidal activity against the intracellular amastigote form in the same order of magnitude as that of the standard drug benznidazole. Furthermore, no appreciable toxicity to mice spleen cells is observed for this compound resulting in a therapeutic index of about 30, which strongly recommends it as a promising candidate for the development of a future antiparasitic drug.

Endothelialization of chitosan porous conduits via immobilization of a recombinant fibronectin fragment (rhFNIII7-10).

The present study aimed to develop a pre-endothelialized chitosan (CH) porous hollowed scaffold for application in spinal cord regenerative therapies. CH conduits with different degrees of acetylation (DA; 4% and 15%) were prepared, characterized (microstructure, porosity and water uptake) and functionalized with a recombinant fragment of human fibronectin (rhFNIII(7-10)). Immobilized rhFNIII(7-10) was characterized in terms of amount ((125)I-radiolabelling), exposure of cell-binding domains (immunofluorescence) and ability to mediate endothelial cell (EC) adhesion and cytoskeletal rearrangement. Functionalized conduits revealed a linear increase in immobilized rhFNIII(7-10) with rhFNIII(7-10) concentration, and, for the same concentration, higher amounts of rhFNIII(7-10) on DA 4% compared with DA 15%. Moreover, rhFNIII(7-10) concentrations as low as 5 and 20µg ml(-1) in the coupling reaction were shown to provide DA 4% and 15% scaffolds, respectively, with levels of exposed cell-binding domains exceeding those observed on the control (DA 4% scaffolds incubated in a 20µg ml(-1) human fibronectin solution). These grafting conditions proved to be effective in mediating EC adhesion/cytoskeletal organization on CH with DA 4% and 15%, without affecting the endothelial angiogenic potential. rhFNIII(7-10) grafting to CH could be a strategy of particular interest in tissue engineering applications requiring the use of endothelialized porous matrices with tunable degradation rates.

[Long-term benzodiazepine use in women at a daycare center for older people]. / O uso prolongado de benzodiazepínicos em mulheres de um centro de convivência para idosos.

While experts recommend caution against long-term benzodiazepine use in the elderly, survey data suggests that the use of benzodiazepine increase with age. The patterns of benzodiazepine use and factors associated with long-term use in population at risk were studied with a standarlized questionnaire applied to 634 women over 60, who attended a daycare center for older people in Rio de Janeiro between May, 1992 and December, 1995. Prevalence of benzodiazepine use in the last 15 days was 21.3% (CI 95% 18.1-24.5), and prevalence of daily use for 12 or more months was 7.4% (CI 95% 5.4-9.4). In a multivaried analysis the amount of drugs being consumed displayed an important and progressive association with long-term benzodiazepine use, with OR = 2.77 (CI 95% 1.17-6.57) for those who take from four to six drugs, and OR = 7.62 (CI 95% 3.18-18.26) for those who take more than seven drugs. Insomnia (OR = 8.87 CI 95% 2.53-31.06) and chronic headache (OR = 3.53 CI 95% 1.82-6.89) have also been associated with this pattern of use.

[Ultrastructural features of cardiac muscle fibers of albino rats during the pregnancy and puerperal cycle]. / Aspectos ultra-estruturais da fibra muscular cardíaca de ratas albinas durante o ciclo gravídico-puerperal.

PURPOSE: In the present study we evaluated the morphology of left ventricular cardiomyocytes of albino rats during pregnancy and puerperium by means of transmission electron microscopy. METHODS: Once pregnancy was confirmed, 77 rats were randomly divided in two groups, respectively, gestation (G) and puerperium (P). The animals of the gestation group were divided into four subgroups, according to gestational age: 1st (G-A), 7th (G-B), 14th (G-C) and 21st (G-D) days of pregnancy. The group defined as puerperium was divided into three subgroups: 7th (P-A), 14th (P-B) and 21st (P-C) days of puerperium. In the end of each established period, the animals were sacrificed and fragments of the medium third of the left ventricle were resected and routinely prepared for electron microscopy analysis. RESULTS: The results obtained with transmission electron microscopy analysis revealed a gradative increase of the cardiomyocytes during pregnancy (increase of myofibrils, which are permeated by numerous mitochondria at the end of gestation). The blood capillary wall showed progressive thinning, with an increase of pynocytotic vesicles in endothelial cells, and intense sarcolemal folding at T-tubule level (capillary tunnels). In the puerperium group, there is a progressive regression in these alterations returning to pre-gestational level at the end of the puerperium cycle. These findings indicate the occurrence of hypertrophy of cardiomyocytes during pregnancy. CONCLUSION: The findings indicate the occurrence of hypertrophy of cardiomyocytes during pregnancy.

Aspectos ultra-estruturais da fibra muscular cardíaca de rats albinas durante o ciclo gravídico-puerperal / Ultrastructural aspects of cardiac muscle fibers of albino rats during pregnancy and puerperal cycle

Objetivo. No presente estudo avalianos, por intermédio da microscopia eletrônica de transmissão, a morfologia dos cardiomiócitos do ventrículo esquerdo de ratas albinas no decorrer do ciclo gravídico-puerperal. Métodos. Obtida a prenhez, 77 ratas foram divididas ao acaso em dois grupos denominados, respectivamente, de: gestação (G) e puerpério (P). Os animais pertencentes ao grupo gestação foram ainda subdivididos em quatro subgrupos, de acordo com a idade gestacional; 1§ (G-A), 7§ (G-B), 14§ (G-C) e 21§ (G-D) dias de prenhez. O grupo definido como puerpério foi também subdividido em três subgrupos; 7§ (P-A), 14§ (P-B) e 21§ (P-C) dias de puerpério. Findo o período estabelecido para cada subgrupo, os animais foram sacrificados, sendo coletados fragmentos do terço médio do ventrículo esquerdo, os quais após processamento apropriado, permitiram observação adequada à microscopia eletrônica de transmissão. Resultados. Os resultados hipertrofia gradativos dos cardiomiócitos no decorrer da prenhez (aumento das miofibrilas, que ao final da gestação apresentaram-se entremeadas de numerosas mitocôndrias). As paredes dos capilares sangüíneos, progressivamente, tornaram-se mais delgadas, com aumento das vesículas de pinocitose no interior das células endoteliais. Revelou ainda, acentuadas dobras do sarcolema em nível dos túbulos T (túneis capilares). No grupo puerpério, notamos gradativa regressão nessas alterações, com retorno às características pré-gestacionais. Os achados demonstram a ocorrência de hipertrofia no decorrer da gestação. Conclusão. Durante a prenhez há hipertrofia em cardiomiócito do ventrículo esquerdo com regressão durante o puerpério.