Immunomodulatory effects of low dose chemotherapy and perspectives of its combination with immunotherapy

Given that cancer is one of the main causes of death worldwide, many efforts have been directed toward discovering new treatments and approaches to cure or control this group of diseases. Chemotherapy is the main treatment for cancer; however, a conventional schedule based on maximum tolerated dose (MTD) shows several side effects and frequently allows the development of drug resistance. On the other side, low dose chemotherapy involves antiangiogenic and immunomodulatory processes that help host to fight against tumor cells, with lower grade of side effects. In this review, we present evidence that metronomic chemotherapy, based on the frequent administration of low or intermediate doses of chemotherapeutics, can be better than or as efficient as MTD. Finally, we present some data indicating that noncytotoxic concentrations of antineoplastic agents are able to both up-regulate the immune system and increase the susceptibility of tumor cells to cytotoxic T lymphocytes. Taken together, data from the literature provides us with sufficient evidence that low concentrations of selected chemotherapeutic agents, rather than conventional high doses, should be evaluated in combination with immunotherapy. Copyright © 2012 UICC.

Immunomodulatory effects of low dose chemotherapy and perspectives of combanation with immunotherapy

Nowadays cancer is one of the main causes of death and many efforts worldwide have been driven to find out new treatments and approaches in order to extinguish or reduce this group of disorder. Chemotherapy is the main treatment for cancer, however, conventional schedule based on maximum tolerated dose (MTD) show several side effects and frequently allow the development of drug resistance. In this review we present the evidence that metronomic chemotherapy, based on the frequent administration of low or intermediate doses of chemotherapeutics is as efficient as MTD and works better in some situations. Finally, we present some data indicating that noncytotoxic concentrations of antineoplastic agents are able to both up-regulate the immune system and increase the susceptibility of tumor cells to cytotoxic T lymphocytes. Taken together, data from the literature provide us the evidence that low concentrations of selected chemotherapeutics agents, rather than conventional high doses, should be chosen for combination with immunotherapy

In vivo genotoxicity assessment of nerolidol

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Genotoxic effects of (-)-cubebin in somatic cells of mice

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Chemomodulation of human dendritic cell function by antineoplastic agents in low noncytotoxic concentrations

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Produção e qualidade fisiológica de sementes de coentro em função de doses de nitrogênio

O objetivo dessa pesquisa foi avaliar o rendimento e a qualidade de sementes de coentro, cultivar Verdão, em função de doses de nitrogênio. Um experimento de campo foi instalado no Centro de Ciências Agrárias da Universidade Federal da Paraíba (CCA-UFPB), em Areia-PB, no período de abril a novembro de 2001, para avaliar a produção de sementes. Os tratamentos consistiram em cinco doses de nitrogênio (0, 20, 40, 60 e 80kg.ha-1) distribuídas em delineamento experimental de blocos casualizados, em quatro repetições. Após as colheitas, as sementes foram avaliadas quanto à qualidade fisiológica (germinação e índice de velocidade de germinação). O rendimento de sementes aumentou com a elevação das doses de nitrogênio, na ordem de 4,7kg.ha-1 a cada quilograma de nitrogênio adicionado ao solo, sendo o rendimento máximo de sementes (1900kg.ha-1), obtido na dose de 80kg.ha-1. A germinação máxima estimada (82%) foi obtida com a dose de 53kg.ha-1 de nitrogênio, enquanto o índice de velocidade de germinação aumentou com a elevação das doses de nitrogênio, sendo verificado um índice de 5,6 na dose máxima de nitrogênio.

Effects of a muscarinic type-2 antagonist on cardiorespiratory function and intestinal transit in horses anesthetized with halothane and xylazine

Objective-To evaluate the cardiorespiratory and intestinal effects of the muscarinic type-2 (M-2) antagonist, methoctramine, in anesthetized horses.Animals-6 horses.Procedure-Horses were allocated to 2 treatments in a randomized complete block design. Anesthesia was maintained with halothane (1% end-tidal concentration) combined with a constant-rate infusion of xylazine hydrochloride (1 mg/kg/h, IV) and mechanical ventilation. Hemodynamic variables were monitored after induction of anesthesia and for 120 minutes after administration of methoctramine or saline (0.9% NaCl) solution (control treatment). Methoctramine was given at 10-minute intervals (10 mug/kg, IV) until heart rate (HR) increased at least 30% above baseline values or until a maximum cumulative dose of 30 mug/kg had been administered. Recovery characteristics, intestinal auscultation scores, and intestinal transit determined by use of chromium oxide were assessed during the postanesthetic period.Results-Methoctramine was given at a total cumulative dose of 30 mug/kg to 4 horses, whereas 2 horses received 10 mug/kg. Administration of methoctramine resulted in increases in HR, cardiac output, arterial blood pressure, and tissue oxygen delivery. Intestinal auscultation scores and intestinal transit time (interval to first and last detection of chromium oxide in the feces) did not differ between treatment groups.Conclusions and Clinical Relevance-Methoctramine improved hemodynamic function in horses anesthetized by use of halothane and xylazine without causing a clinically detectable delay in the return to normal intestinal motility during the postanesthetic period. Because of their selective positive chronotropic effects, M-2 antagonists may represent a safe alternative for treatment of horses with intraoperative bracycardia.

Effects of glycopyrrolate on cardiorespiratory function in horses anesthetized with halothane and xylazine

Objective-To evaluate cardiopulmonary effects of glycopyrrolate in horses anesthetized with halothane and xylazine.Animals-6 horses.Procedure-Horses were allocated to 2 treatment groups in a randomized complete block design. Anesthesia was maintained in mechanically ventilated horses by administration of halothane (1% end-tidal concentration) combined with a constant-rate infusion of xylazine hydrochloride (1 mg/kg/h, IV). Hemodynamic variables were monitored after induction of anesthesia and for 120 minutes after administration of glycopyrrolate or saline (0.9% NaCl) solution. Glycopyrrolate (2.5 mug/kg, IV) was administered at 10-minute intervals until heart rate (HR) increased at least 30% above baseline or a maximum cumulative dose of 75 mug/kg had been injected. Recovery characteristics and intestinal auscultation scores were evaluated for 24 hours after the end of anesthesia.Results-Cumulative dose of glycopyrrolate administered to 5 horses was 5 mug/kg, whereas 1 horse received 75 mug/kg. The positive chronotropic effects of glycopyrrolate were accompanied by an increase in cardiac output, arterial blood pressure, and tissue oxygen delivery. Whereas HR increased by 53% above baseline values at 20 minutes after the last glycopyrrolate injection, cardiac output and mean arterial pressure increased by 38% and 31%, respectively. Glycopyrrolate administration was associated with impaction of the large colon in I horse and low intestinal auscultation scores lasting 24 hours in 3 horses.Conclusions and Clinical Relevance-The positive chronotropic effects of glycopyrrolate resulted in improvement of hemodynamic function in horses anesthetized with halothane and xylazine. However, prolonged intestinal stasis and colic may limit its use during anesthesia.

Método de pontos interiores no planejamento ótimo do tratamento de câncer por radioterapia

The Medical Physics has been developing very fast due to the progress of the technologies and to the increase of the concerns with cure of diseases. One of the Medical Physics main performances at the present time is the use of ionizing radiations for cancer treatment, especially, services as Radiotherapy. The radiotherapy technique uses ionizing radiation with therapeutic end of cancer controls, avoiding your proliferation and it worsens of the patient. For the treatment a radiation bunch is used, with rectangular form, that it passes through the different types of tissues of the patient's body, and depending on the attenuation and of the depth of the fabrics, a great amount of energy is deposited inside in different points of the body. Like this, to plan this treatment type it should be obtained the dimension of the distribution and dose absorption along the volume. For this, it is necessary in the planning of the treatment of the cancer for radiotherapy to build isodose curves, which are lines that represent points of same amount of dose to be deposited in the area to be treated. To aid the construction of the curves of form isodose to reach the best result in the planning of the treatment, in other words, a great planning, providing the maximum of dose in the tumor and saving the healthy and critical organs, it has been using mathematical tools and computational. A plan of cancer treatment for radiotherapy is considered great when all the parameters that involve the treatment, be them physical or biological, they were investigated and adapted individually for the patient. For that, is considered the type and the location of the tumor, worrying about the elimination of the cancer without damaging the healthy tissue of the treated area, mainly the risk organs, which are in general very sensitive to the radiations. This way, the optimization techniques... (Complete abstract click electronic access below)

Determination of the highest no-effect dose (HNED) and of the elimination pattern for cocaine in horses

Cocaine is one of the most widespread illegal stimulants utilized by the human population throughout the world. The aim of this study was to establish the highest no-effect dose (HNED) of cocaine on the spontaneous locomotor activity (SLA) of horses in a behavior chamber, and thereby to determine the maximal acceptable threshold of the urinary drug concentration in horses. Twelve English thoroughbred mares received 0.02, 0.03, 0.04, 0.08 or 0.12 mg kg(-1) cocaine i.v. or saline solution (control). It was noted that doses above 0.04 mg kg(-1) induced a significant increase in SLA (P < 0.05, Tukey's test). No significant increase in SLA was seen in the mares that received 0.03 mg kg(-1), but the animals showed important behavioral changes that did not occur after the 0.02 mg kg(-1) dose. It was concluded that the HNED of cocaine for horses in a behavior chamber is 0.02 mg kg(-1). After injection of this dose in five horses, urine samples were collected at predetermined intervals through vesical catheterization. The concentrations of cocaine, norcocaine, benzoylecgonine and ecgonine methyl ester were quantified by liquid chromatography/electrospray ionization tandem mass spectrometry. Cocaine and norcocaine concentrations remained consistently below the level of detection. Benzoylecgonine reached a mean (+/- SEM) maximum concentration of 531.9 +/- 168.7 ng ml(-1) after 4 h, whereas ecgonine methyl ester peaked 2 h after injection at a concentration of 97.2 +/- 26.5 ng ml(-1). The maximum admissible concentration for cocaine and/or metabolites in the urine of horses is difficult to establish unequivocally because of the substantial individual variation in the drug elimination pattern observed in horses, which can be inferred by the large standard error of the means obtained. Copyright (C) 2002 John Wiley Sons, Ltd.

Efeitos da irrigação e adubação nitrogenada sobre a massa de forragem de cultivares de Panicum maximum Jacq.

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Produção e composição bromatológica da forragem do capim-mombaça (Panicum maximum Jacq.), submetidos a diferentes fontes e doses de corretivo de acidez

The experiment was carried in protected (greenhouse) atmosphere, in University of Engineering, UN-ESP of Ilha Solteira-SP, with the objective of evaluating sources (limestone and calcium silicate slag) and doses (0,0 0,5 1,0 1,5 2,0 times the recommended dose) of corrective in the bromatolouic composition, tillering and production of dry matter of the grass mombaca (Nuncio? maximum Jacq.). The lineation was completely randomized design, with four repetitions. It was evaluated the tiller number, the production of dry matter, the gross protein, neutral detergent fiber (NDF) and acid detergent fiber (ADF). The corrective influenced the tillering in almost all of the countings. The limestone provided larger production of dry matter in the doses of 1,5 and 2,0 times the recommended dose. The bromatologic composition of the forage was not influenced by the corrective and doses.

Sistema radicular do Panicum maximum Jacq. cv. IPR-86 Milênio adubado com nitrogênio e submetido à lotação rotacionada

Avaliou-se o efeito do nitrogênio no sistema radicular da espécie Panicum maximum Jacq. cv. IPR-86 Milênio, sob pastejo. As doses de N utilizadas foram 0; 150; 300 e 450 kg/ha.ano. As densidades de raízes no pré-pastejo foram avaliadas no quinto ano de aplicação de N, em três profundidades (0-10; 10-20 e 20-40 cm), com crescimento aos 7; 14; 21 e 35 dias após o pastejo. O método de pastejo utilizado foi o de lotação rotacionada. Os valores máximos de densidades de comprimento e de massa das raízes no pré e no pós-pastejo foram obtidos nas doses de N de 204; 206; 192 e 197 kg/ha, respectivamente. Nas doses de N de 0, 150 e 300 kg/ha, o crescimento das raízes (em densidade de comprimento) aumentou, em média, até 29 dias após o pastejo, enquanto, na dose 450 kg/ha, o aumento foi linear. Independentemente da dose de N, 60 a 25% do sistema radicular do cultivar IPR-86 Milênio concentrou-se nas camadas de 0-10 e 10-20 cm de profundidade, respectivamente.

Poly [1,1'-bis(ethynyl)-4,4'-biphenyl(bis-tributylphosphine)Pt(II)] solutions used as low dose ionizing radiation dosimeter

In this work, the effect of gamma radiation on the optical properties of polymetallayne poly[1,1'-bis(ethynyl)-4,4'-biphenyl(bis-tributylphosphine)Pt(II) ] (Pt-DEBP) in chloroform solution is studied. The samples were irradiated at room temperature with doses from 0.01 Gy to 1 Gy using a 60Co gamma ray source. A new band at 420 nm is observed in the emission spectra, in superposition to the emission maximum at 398 nm, linearly dependent on dose. We propose to use the ratio of the emission amplitude bands as the dosimetric parameter. This method proved to be robust, accurate, and can be used as a dosimeter in medical applications. © 2013 AIP Publishing LLC.

Coletores de amônia, fontes e formas de aplicação de nitrogênio em Panicum maximum CV. Tanzânia submetido a manejo intensivo

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