Evaluation of tumor growth remission in a murine model for subcutaneous solid tumors - Benefits of associating the antitumor agent crotamine with mesoporous nanosilica particles to achieve improved dosing frequency and efficacy.

Crotamine is a highly cationic polypeptide first isolated from South American rattlesnake venom, which exhibits affinity for acidic lysosomal vesicles and proliferating cells. This cationic nature is pivotal for its in vitro cytotoxicity and in vivo anticancer actions. This study aimed to enhance the antitumor efficacy of crotamine by associating it with the mesoporous SBA-15 silica, known for its controlled release of various chemical agents, including large proteins. This association aimed to mitigate the toxic effects while amplifying the pharmacological potency of several compounds. Comprehensive characterization, including transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential analysis, confirmed the successful association of crotamine with the non-toxic SBA-15 nanoparticles. The TEM imaging revealed nanoparticles with a nearly spherical shape and variations in uniformity upon crotamine association. Furthermore, DLS showed a narrow unimodal size distribution, emphasizing the formation of small aggregates. Zeta potential measurements indicated a distinct shift from negative to positive values upon crotamine association, underscoring its effective adsorption onto SBA-15. Intraperitoneal or oral administration of crotamine:SBA-15 in a murine melanoma model suggested the potential to reduce the frequency of crotamine doses without compromising efficacy. Interestingly, while the oral route enhanced the antitumor efficacy of crotamine, pH-dependent release from SBA-15 was observed. Thus, associating crotamine with SBA-15 could reduce the overall required dose to inhibit solid tumor growth, bolstering the prospect of crotamine as a potent anticancer agent.

Evaluation of tumor growth remission in a murine model for subcutaneous solid tumors, benefits of associating the antitumor agent crotamine with mesoporous nanosilica particles to achieve improved dosing frequency and efficacy

Crotamine is a highly cationic polypeptide first isolated from South American rattlesnake venom, which exhibits affinity for acidic lysosomal vesicles and proliferating cells. This cationic nature is pivotal for its in vitro cytotoxicity and in vivo anticancer actions. This study aimed to enhance the antitumor efficacy of crotamine by associating it with the mesoporous SBA-15 silica, known for its controlled release of various chemical agents, including large proteins. This association aimed to mitigate the toxic effects while amplifying the pharmacological potency of several compounds. Comprehensive characterization, including transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential analysis, confirmed the successful association of crotamine with the non-toxic SBA-15 nanoparticles. The TEM imaging revealed nanoparticles with a nearly spherical shape and variations in uniformity upon crotamine association. Furthermore, DLS showed a narrow unimodal size distribution, emphasizing the formation of small aggregates. Zeta potential measurements indicated a distinct shift from negative to positive values upon crotamine association, underscoring its effective adsorption onto SBA-15. Intraperitoneal or oral administration of crotamine:SBA-15 in a murine melanoma model suggested the potential to reduce the frequency of crotamine doses without compromising efficacy. Interestingly, while the oral route enhanced the antitumor efficacy of crotamine, pH-dependent release from SBA-15 was observed. Thus, associating crotamine with SBA-15 could reduce the overall required dose to inhibit solid tumor growth, bolstering the prospect of crotamine as a potent anticancer agent.

Evaluation of tumor growth remission in a murine model for subcutaneous solid tumors, benefits of associating the antitumor agent crotamine with mesoporous nanosilica particles to achieve improved dosing frequency and efficacy

Crotamine is a highly cationic polypeptide first isolated from South American rattlesnake venom, which exhibits affinity for acidic lysosomal vesicles and proliferating cells. This cationic nature is pivotal for its in vitro cytotoxicity and in vivo anticancer actions. This study aimed to enhance the antitumor efficacy of crotamine by associating it with the mesoporous SBA-15 silica, known for its controlled release of various chemical agents, including large proteins. This association aimed to mitigate the toxic effects while amplifying the pharmacological potency of several compounds. Comprehensive characterization, including transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential analysis, confirmed the successful association of crotamine with the non-toxic SBA-15 nanoparticles. The TEM imaging revealed nanoparticles with a nearly spherical shape and variations in uniformity upon crotamine association. Furthermore, DLS showed a narrow unimodal size distribution, emphasizing the formation of small aggregates. Zeta potential measurements indicated a distinct shift from negative to positive values upon crotamine association, underscoring its effective adsorption onto SBA-15. Intraperitoneal or oral administration of crotamine:SBA-15 in a murine melanoma model suggested the potential to reduce the frequency of crotamine doses without compromising efficacy. Interestingly, while the oral route enhanced the antitumor efficacy of crotamine, pH-dependent release from SBA-15 was observed. Thus, associating crotamine with SBA-15 could reduce the overall required dose to inhibit solid tumor growth, bolstering the prospect of crotamine as a potent anticancer agent.

Impact of emergency short-stay unit opening on in-hospital global and cardiology indicators.

RATIONALE, AIMS AND OBJECTIVES: Emergency short-stay unit (SSU) alleviates emergency department (ED) overcrowding, but may affect in-hospital indicators. Cardiology patients comprise a substantial part of patients admitted at SSU. This study evaluated whether SSU opening differentially modified in-hospital indicators at a whole general hospital and at its cardiology division (CARD). METHODS: We retrospectively analysed indicators based on 859 686 ED visits, and 171 547 hospital admissions, including 12 110 CARD admissions, from 2007 to 2018 at a general tertiary hospital, and compared global ED indicators and in-hospital indicators at the hospital and CARD before (2007-2011) and after (2011-2018) SSU opening. RESULTS: After SSU opening, monthly ED bed occupancy rate decreased (mean ± SD 200 ± 18% vs 187 ± 22%; P < .001) and in-hospital admissions from ED increased at the hospital (median [interquartile range] 460 [81] vs 524 [41], P < .001) and CARD (50 [12] vs 54 [12], P = .004). In parallel, monthly in-hospital elective admissions decreased at CARD (34 [18] vs 28 [17], P = .019), but not at the hospital (712 [73] vs 700 [104], P = .54). Average length of stay (LOS) increased at both hospital (8.5 ± 0.3 vs 8.7 ± 0.4 days, P < .001) and CARD (9.2 ± 1.5 vs 10.3 ± 2.3 days, P = .002) after SSU opening, but percent admissions at SSU showed a direct relationship with LOS solely at CARD. Furthermore, cardiology patients admitted at SSU had greater LOS, prevalence of coronary heart disease and age than those admitted at the conventional cardiology ward. CONCLUSIONS: SSU opening improved ED crowding, but was associated with changes in in-hospital indicators, particularly at CARD, and in the characteristics of hospitalized cardiology patients. These findings suggest that in-hospital cardiology services may need re-evaluation following SSU opening at a general hospital.

Impact of percentage and particle size of sugarcane biochar on the sorption behavior of clomazone in Red Latosol.

Biochar is a carbonaceous material that has excellent potential as a fertilizer and soil conditioner. However, there is a lack of information concerning the effects of the amount and particle size of this pyrogenic material on the soil sorption capacity. In this work, evaluation was made of changes in clomazone (CMZ) sorption in a Red Latosol following soil conditioning using different percentages (0.25, 0.5, and 1% w/w) of sugarcane biochar in three particle sizes (<106, 106-508, and 508-610 µm). The conditioned soils presented apparent sorption coefficients (Kd) up to 1300 times higher than that of pure soil, besides changes in the behavior of CMZ sorption. The biochar particle size and percentage influenced sorption of the herbicide as well as its retention in the amended soil during desorption processes. Both sorption and desorption Freundlich constants were linearly correlated with the external surface area of the biochar present in the soil.

Liquid chromatographic determination of norfloxacin in extended-release tablets.

A stability indicating reversed-phase liquid chromatography method is developed and validated for the determination of norfloxacin in a new formulation of extended-release tablets. The LC method is carried out on a Luna C(18) column (150 x 4.6 mm) maintained at 40 degrees C. The mobile phase is composed of phosphate buffer (0.04 M, pH 3.0)-acetonitrile (84:16, v/v) run at a flow rate of 1.0 mL/min and detection at 272 nm. The chromatographic separation was obtained within 10 min, and it is linear in the concentration range of 0.05-5 microg/mL. Validation parameters, such as the specificity, linearity, precision, accuracy, and robustness, were evaluated, and results were within the acceptable range. Moreover, the proposed method was successfully applied for the assay of norfloxacin in the developed formulations.

Utilização do osso alógeno em bloco para aumento de rebordo alveolar: revisão da literatura / The use of allogeneic bone block for alveolar ridge augmentation: a literature review

Apesar da segurança proporcionada pelo osso autógeno para a correção de defeitos alveolares é constante a busca de alternativas que eliminem ou diminuam a morbidade de uma segunda região operada. Com o advento das técnicas de regeneração óssea guiada é também crescente o interesse pelo uso do osso alógeno. Este trabalho tem por objetivo fazer uma revisão da literatura sobre o uso do osso alógeno em bloco para a reconstrução de rebordos alveolares deficientes, associado ao tratamento com implantes dentários.

Effect of one month ketoconazole treatment on GH, cortisol and ACTH release after ghrelin, GHRP-6 and GHRH administration in patients with Cushing's disease.

GH responses to ghrelin, GHRP-6, and GHRH in Cushing's disease (CD) are markedly blunted. There is no data about the effect of reduction of cortisol levels with steroidogenesis inhibitors, like ketoconazole, on GH secretion in CD. ACTH levels during ketoconazole treatment are controversial. The aims of this study were to compare the GH response to ghrelin, GHRP-6, and GHRH, and the ACTH and cortisol responses to ghrelin and GHRP-6 before and after one month of ketoconazole treatment in 6 untreated patients with CD. Before treatment peak GH (microg/L; mean +/- SEM) after ghrelin, GHRP-6, and GHRH administration was 10.0 +/- 4.5; 3.8 +/- 1.6, and 0.6 +/- 0.2, respectively. After one month of ketoconazole there was a significant decrease in urinary cortisol values (mean reduction: 75%), but GH responses did not change (7.0 +/- 2.0; 3.1 +/- 0.8; 0.9 +/- 0.2, respectively). After treatment, there was a significant reduction in cortisol (microg/dL) responses to ghrelin (before: 30.6 +/- 5.2; after: 24.2 +/- 5.1). No significant changes in ACTH (pg/mL) responses before (ghrelin: 210.9 +/- 69.9; GHRP-6: 199.8 +/- 88.8) and after treatment (ghrelin: 159.7 +/- 40.3; GHRP-6: 227 +/- 127.2) were observed. In conclusion, after short-term ketoconazole treatment there are no changes in GH or ACTH responses, despite a major decrease of cortisol levels. A longer period of treatment might be necessary for the recovery of pituitary function.

Effect of one month ketoconazole treatment on GH, cortisol and ACTH release after ghrelin, GHRP-6 and GHRH administration in patients with cushing’s disease

GH responses to ghrelin, GHRP-6, and GHRH in Cushing’s disease (CD) are markedly blunted. There is no data about the effect of reduction of cortisol levels with steroidogenesis inhibitors, like ketoconazole, on GH secretion in CD. ACTH levels during ketoconazole treatment are controversial. The aims of this study were to compare the GH response to ghrelin, GHRP-6, and GHRH, and the ACTH and cortisol responses to ghrelin and GHRP-6 before and after one month of ketoconazole treatment in 6 untreated patients with CD. Before treatment peak GH (mg/L; mean ± SEM) after ghrelin, GHRP-6, and GHRH administration was 10.0 ± 4.5; 3.8 ± 1.6, and 0.6 ± 0.2, respectively. After one month of ketoconazole there was a significant decrease in urinary cortisol values (mean reduction: 75 percent), but GH responses did not change (7.0 ± 2.0; 3.1 ± 0.8; 0.9 ± 0.2, respectively). After treatment, there was a significant reduction in cortisol (mg/dL) responses to ghrelin (before: 30.6 ± 5.2; after: 24.2 ± 5.1). No significant changes in ACTH (pg/mL) responses before (ghrelin: 210.9 ± 69.9; GHRP-6: 199.8 ± 88.8) and after treatment (ghrelin: 159.7 ± 40.3; GHRP-6: 227 ± 127.2) were observed. In conclusion, after short-term ketoconazole treatment there are no changes in GH or ACTH responses, despite a major decrease of cortisol levels. A longer period of treatment might be necessary for the recovery of pituitary function.

Na doença de Cushing (DC), as respostas do GH à ghrelina, ao GHRP-6 e ao GHRH estão diminuídas. Não existem dados sobre o efeito da redução dos níveis de cortisol, após cetoconazol, na secreção de GH na DC. Nessa situação, os níveis de ACTH são variáveis. Os objetivos do estudo são comparar as respostas do GH à administração de ghrelina, GHRP-6 e GHRH, e de ACTH e cortisol à ghrelina e ao GHRP-6 antes e após um mês de tratamento com cetoconazol em 6 pacientes com DC não tratados. Antes do tratamento, o pico de GH (mg/L; média ± EPM) após a administração de ghrelina, GHRP-6 e GHRH foi de 10,0 ± 4,5; 3,8 ± 1,6 e 0,6 ± 0,2, respectivamente. Após um mês de cetoconazol, ocorreu diminuição significante do cortisol urinário (redução média: 75 por cento), mas as respostas de GH permaneceram inalteradas (7,0 ± 2,0; 3,1 ± 0,8; 0,9 ± 0,2, respectivamente). Após o tratamento, houve redução da resposta de cortisol (mg/dL) à ghrelina (antes: 30,6 ± 5,2; após: 24,2 ± 5,1), mas não ocorreram mudanças nas respostas de ACTH (pg/mL) (ghrelina antes: 210,9 ± 69,9; após: 159,7 ± 40,3; GHRP-6 antes: 199,8 ± 88,8; após: 227 ± 127,2). Assim, o tratamento a curto prazo com cetoconazol não modificou as respostas de GH ou ACTH, apesar da redução do cortisol. Para a recuperação da função hipofisária deve ser necessário um período de tratamento maior.