Humanismo, medicina y sociedad en el pensamiento de Fidel Castro

Estudiar el humanismo exterioriza cualquier directriz de pensamiento que ratifique la dignidad del ser humano. Sobre esta base, se puede desentrañar al humanismo de las formas más diversas. Las grandes dimensiones del pensamiento humanista de Fidel Castro Ruz, parten de la convicción de justicia social como un medio de reivindicación, sobre la base de la igualdad. El presente trabajo, demuestra a través de discursos y reflexiones de Fidel Castro Ruz, sobre la sociedad y la medicina, su visión humanista. Se emplearon métodos del nivel teórico, particularmente el histórico lógico y del nivel empírico, la revisión de fuentes documentales. Se han referenciado 22 documentos, que refieren el legado histórico de la obra de Fidel Castro. En ella se demuestra su proyección, su lucha contra las adversidades, por lograr los cambios necesarios en la sociedad cubana, contribuir al mejoramiento de los pueblos y en particular es reconocida en ella, su preocupación por la salud de todos, la ética, la solidaridad, la fidelidad, la honestidad con la historia y sobre todo, su percepción perenne en aras del bienestar de la humanidad.

Studying humanism externalizes any guideline of thought, which enphasize the dignity of the human being. On this basis, humanism can be unraveled in the most diverse ways. The great dimensions of humanist thought of Fidel Castro Ruz, start from the conviction of social justice as a means of vindication, on the basis of equality. The present study demonstrates, through speeches and reflections of Fidel Castro Ruz, about science and medicine, his humanistic vision. Methods of the theoretical level were used, particularly the logical historical one; and from the empirical level, the review of documentary sources. 22 documents have been referenced, which refer to the historical legacy of the work of Fidel Castro. Through his works we can see his projection, his struggle against adversity, to achieve the necessary changes in Cuban society, contributing to the improvement of the peoples and, in special, his concern for the health of all, ethics, solidarity, fidelity, honesty with history and above all, its perennial perception for the welfare of humanity.

Adsorption of congo red dye from aqueous solution onto amino-functionalized silica gel / Adsorção do corante vermelho congo em solução aquosa com sílica aminofuncionalizada

ABSTRACT This study investigates the potential use of amino-functionalized silica gel as an adsorbent for the recovering of congo red dye from aqueous solution. The effects of pH, contact time, and temperature were determined and evaluated. Equilibrium isotherms were also studied. The adsorption kinetics was modeled by pseudo-first order and pseudo-second order. Furthermore, desorption of congo red was preliminarily studied. The pH range from 4.5 to 7.0 was favorable for the adsorption of congo red onto amine modified silica at 25ºC. Higher adsorption capacity was obtained at 50ºC. Langmuir and Freundlich models were fitted to the adsorption equilibrium data. The best fittings were obtained with the pseudo-second order and Langmuir model for kinetics and equilibrium, respectively. Desorption studies suggest that ion exchange might be the major mode of adsorption. KOH solution was the best desorbing agent for recovering the adsorbed dye.

RESUMO Este estudo investiga o potencial uso de sílica gel aminofuncionalizada como adsorvente para a recuperação de corante vermelho congo em solução aquosa. Efeitos do pH, do tempo de contato e da temperatura foram determinados e avaliados. As isotermas de equilíbrio também foram estudadas. A cinética de adsorção foi modelada por pseudoprimeira ordem e pseudossegunda ordem. Além disso, a dessorção do vermelho congo foi preliminarmente estudada. O intervalo de pH de 4,5 a 7,0 foi favorável para a adsorção do corante pela sílica modificada com amina a 25ºC. Obteve-se maior capacidade de adsorção a 50ºC. Modelos de Langmuir e Freundlich foram ajustados aos dados de equilíbrio de adsorção. Os melhores resultados foram obtidos com a pseudossegunda ordem e o modelo de Langmuir para cinética e equilíbrio, respectivamente. Estudos de dessorção sugerem que a troca iônica pode ser o principal modo de adsorção. O hidróxido de potássio foi o melhor agente de dessorção para recuperar o corante adsorvido.

Towards an age-dependent transmission model of acquired and sporadic Creutzfeldt-Jakob disease.

INTRODUCTION: Sporadic Creutzfeldt-Jakob disease (sCJD) might be transmitted by surgery. The purpose of this study was to investigate potential susceptibility to sCJD from surgery at juvenile age and in early adulthood. METHODS: From Danish and Swedish national registries we identified 167 definite and probable sCJD cases with onset from 1987 through 2003, and 835 age-, sex- and residence-matched controls along with their surgical histories. Main, anatomically or etiologically classified surgical procedures followed by a ≥20-year lag were analyzed using logistic regression, and stratified by age at first-registered surgical discharge. RESULTS: The risk of having a diagnosis of CJD depended strongly on age at first surgery with odds ratio (OR) of 12.80 (95% CI 2.56-64.0) in patients <30 years, 3.04 (95% 1.26-7.33) in 30-39 years, and 1.75 (95% CI 0.89-3.45) in ≥40 years, for anatomically classified surgical procedures. Similar figures were obtained for etiologically classified surgical procedures. CONCLUSIONS: Risk of surgical-acquired sCJD depends on age at exposure; this pattern is similar to age-specific profiles reported for CJD accidentally transmitted by human pituitary-derived growth hormone and susceptibility curves for variant CJD estimated after adjustment for dietary exposure to bovine spongiform encephalopathy. There might be an age-at-exposure-related susceptibility to acquire all CJD forms, including sCJD from routine surgery.

Translational gap in glioma research.

During the last five decades, enormous advances in treatment modalities for cancer and a better understanding of cancer cell biology have been accomplished but the prognosis of patients carrying malignant gliomas still remains poor despite hundreds of clinical trials have been carried out. In this article we review phase II clinical trials that have been completed and published in PubMed during 2011 in order to investigate potential reasons of clinical failure. We suggest that a translational gap, defined as a failure to translate basic research into clinical trials design may explain the poor outcome of phase II clinical trials.

Late-in-life surgery associated with Creutzfeldt-Jakob disease: a methodological outline for evidence-based guidance.

BACKGROUND: There is increasing epidemiological evidence of etiological links between general surgery and sporadic Creutzfeldt-Jakob disease (sCJD) with long incubation periods. The purpose of this study was to identify specific surgical procedures potentially associated with sCJD to be targeted for preventive presurgical-intervention guidance. RESULTS: We propose a three-step clinical guidance outline where surgical procedures associated with sCJD clinical onset - potentially more contaminant - are taken into account. Data on hospital discharges and surgical procedures were obtained from Danish and Swedish national in-patient hospital registries for 167 sCJD cases, onset 1987-2003, and for 835 matched and 2,224 unmatched population controls. Surgery was allocated to different life-time periods as previously reported, and frequencies were compared using logistic regression analysis. In the year preceding clinical onset, persons with sCJD underwent a statistically significant higher number of minor surgical interventions (OR (95% CI): 17.50 (3.64-84.24)), transluminal endoscopies (OR: 2.73 (1.01-7.37)) and gastrointestinal operations (OR: 3.51 (1.21-10.19)) compared to matched controls. Surgical discharges clustered towards clinical onset. These differences increased during the clinical period, with statistically significant higher frequencies for both endoscopies and minor surgery (OR: 13.91 (5.87-32.95), and for main surgical procedures (OR: 2.10 (1.00-4.39)), particularly gastrointestinal surgery (OR: 6.00 (1.83-19.66)), and surgery contacting skeletal muscle. Comparisons with unmatched controls yielded similar results for neurosurgery in the clinical period (OR: 19.40 (2.22-168.34)). CONCLUSIONS: These results suggest that some types of surgical procedures are associated with sCJD, after clinical onset or particularly just before onset. Selective planning of such surgery to minimize instrument/device contamination or quarantining might be feasible. Conditional to progress in sCJD etiological research, results are relevant for guidance development.

Menadione : sodium orthovanadate combination eliminates and inhibits migration of detached cancer cells.

Exposure of cancer cells to anticancer agents in cultures induces detachment of cells that are usually considered dead. These drug-induced detached cells (D-IDCs) may represent a clinical problem for chemotherapy since they may survive anoikis, enter the circulation, invade other tissues and resume proliferation, creating a metastasis, especially in tissues where the bioavailability of anticancer agents is not enough to eliminate all cancer cells. In this study we evaluated the antiproliferative effect of menadione : sodium orthovanadate (M : SO) combination on A549 lung cancer cells as well as the ability of M : SO to induce cell detachment. In addition, we followed the fate and chemosensitivity of M : SO-induced detached cells. Using transwell chambers, we found that a fraction of the M : SO-induced detached cells were viable and, furthermore, were able to migrate, re-attach, and resume proliferation when re-incubated in drug-free media. The total elimination of A549 detachment-resistant cells and M : SO-induced detached cells were successfully eliminated by equivalent M : SO concentration (17.5 µM : 17.5 µM). Thus, M : SO prevented cell migration. Similar results were obtained on DBTRG.05MG human glioma cells. Our data guarantee further studies to evaluate the in vivo occurrence of D-IDCs, their implications for invasiveness and metastasis and their sensitivity to anticancer drugs.

Cytotoxic effect of menadione and sodium orthovanadate in combination on human glioma cells.

Gliomas are the most common primary brain tumor, and their treatment is still a challenge. Here, we evaluated the antiproliferative effect of a novel combination of two potent oxidative stress enhancers: menadione (M) and sodium orthovanadate (SO). We observed both short-term and prolonged growth inhibitory effects of M or SO alone as well as in combination (M:SO) on DBTRG.05MG human glioma cells. A stronger antiproliferative effect was observed in the short-term proliferation assay with the M:SO combination compared to either investigated agent alone. In the long-term proliferation assay, a 10-day exposure to M:SO at concentrations of 10 µM:17.5 µM or 17.5 µM:10 µM was enough to kill 100% of the cells; no cell regrowth was observed after re-incubation in drug-free media. When used in combination, the single concentration of M and SO could be decreased by 2.5- to 5-fold of those used for each experimental drug alone and still obtain a similar antiproliferative effect. The underlying molecular mechanism was investigated by co-incubating M:SO with dithiothreitol (DTT) and genistein. Both substances partially neutralized the effects of the M:SO combination, showing additive effects. This observation suggests a role of oxidative stress and tyrosine kinase stimulation in the M:SO cytotoxic effect. Our results indicate that M:SO combination is an attractive alternative for glioma treatment that encourages further study. The neutralizing effects of genistein and DTT reveal a possibility for their use in the minimization of potential M:SO systemic toxicity.

In vitro inhibition of topoisomerase IIα by reduced glutathione.

In most cells, the major intracellular redox buffer is glutathione (GSH) and its disulfide-oxidized (GSSG) form. The GSH/GSSG system maintains the intracellular redox balance and the essential thiol status of proteins by thiol disulfide exchange. Topoisomerases are thiol proteins and are a target of thiol-reactive substances. In this study, the inhibitory effect of physiological concentration of GSH and GSSG on topoisomerase IIα activity in vitro was investigated. GSH (0-10 mM) inhibited topoisomerase IIα in a concentration-dependent manner while GSSG (1-100 µM) had no significant effect. These findings suggest that the GSH/GSSG system could have a potential in vivo role in regulating topoisomerase IIα activity.

Pankiller effect of prolonged exposure to menadione on glioma cells: potentiation by vitamin C.

Menadione (Vitamin K3) has anti-tumoral effects against a wide range of cancer cells. Its potential toxicity to normal cells and narrow therapeutic range limit its use as single agent but in combination with radiation or other anti-neoplastic agents can be of therapeutic use. In this paper, we first evaluated the early (within 3 h) effect of menadione on ongoing DNA replication. In normal rat cerebral cortex mini-units menadione showed an age dependent anti-proliferative effect. In tissue mini-units prepared from newborn rats, menadione inhibited ongoing DNA replication with an IC (50) of approximately 10 µM but 50 µM had no effect on mini-units from prepared adult rat tissue. The effect of short (72 h) and prolonged exposure (1-2 weeks) to menadione alone in the DBTRG.05MG human glioma cells line and in combination with vitamin C was studied. After short period of exposure data show that menadione alone or in combination with vitamin C provided similar concentration-response curves (and IC(50) values). Prolonged exposure to these drugs was evaluated by their ability to kill 100% of glioma cells and prevent regrowth when cells are re-incubated in drug-free media. In this long-term assay, menadione:vitamin C at a ratio 1:100 showed higher anti-proliferative activity when compared to each drug alone and allowed to reduce each drug concentration between 2.5 to 5-fold. Similar anti-proliferative effect was demonstrated in 8 patient derived glioblastoma cell cultures. Our data should be able to encourage further advanced studies on animal models to evaluate the potential use of this combination therapy for glioma treatment.

Nosocomial transmission of sporadic Creutzfeldt-Jakob disease: results from a risk-based assessment of surgical interventions.

OBJECTIVES: Evidence of surgical transmission of sporadic Creutzfeldt-Jakob disease (sCJD) remains debatable in part due to misclassification of exposure levels. In a registry-based case-control study, the authors applied a risk-based classification of surgical interventions to determine the association between a history of surgery and sCJD. DESIGN: Case-control study, allowing for detailed analysis according to time since exposure. SETTING: National populations of Denmark and Sweden. PARTICIPANTS: From national registries of Denmark and Sweden, the authors included 167 definite and probable sCJD cases with onset during the period 1987-2003, 835 age-, sex- and residence-matched controls and 2224 unmatched. Surgical procedures were categorised by anatomical structure and presumed risk of transmission level. The authors used logistic regression to determine the odds ratio (OR) for sCJD by surgical interventions in specified time-windows before disease-onset. RESULTS: From comparisons with matched controls, procedures involving retina and optic nerve were associated with an increased risk at a latency of ≥1 year OR (95% CI) 5.53 (1.08 to 28.0). At latencies of 10 to 19 years, interventions on peripheral nerves 4.41 (1.17 to 16.6) and skeletal muscle 1.58 (1.01 to 2.48) were directly associated. Interventions on blood vessels 4.54 (1.01 to 20.0), peritoneum 2.38 (1.14 to 4.96) and skeletal muscle 2.04 (1.06 to 3.92), interventions conducted by vaginal approach 2.26 (1.14 to 4.47) and a pooled category of lower-risk procedures 2.81 (1.62 to 4.88) had an increased risk after ≥20 years. Similar results were found when comparing with unmatched controls. INTERPRETATION: This observation is in concordance with animal models of prion neuroinvasion and is likely to represent a causal relation of surgery with a non-negligible proportion of sCJD cases.

Strong inhibition of replicative DNA synthesis in the developing rat cerebral cortex and glioma cells by roscovitine.

The effects of the cyclin-dependent kinase inhibitors roscovitine and olomoucine on DNA synthesis rate during normal rat brain development were studied by using short time (90 min) incubation. Both purine analogues at 100 microM concentration decreased the DNA synthesis of rat cerebral cortex in an age-dependent manner. The maximum inhibitory effect (approximately 90% for roscovitine, approximately 60% for olomoucine) occurred in rats of 2-13 days postnatal age. In adult rats (> 60 days postnatal age), the effect of both purine analogues was low. Roscovitine even at 200 microM concentration did not inhibit the fraction of DNA synthesis insensitive to hydroxyurea (unscheduled DNA synthesis (UDS)). In addition, in the RG2 rat glioma model, roscovitine produced a strong inhibition of DNA synthesis in glioma cells when compared to adult normal tissue. Since in adult rat brain more than 60% of DNA synthesis is related to DNA repair, usually measured as UDS, our results indicate that roscovitine strongly blocks ongoing DNA synthesis connected with replicative processes.

Ongoing DNA synthesis in the rat cerebral cortex is regulated by a proteolytic pathway independent of the proteasome and calpains.

By using mini-units of tissue and protease inhibitors in short term incubation (0-180 min), we studied the role of proteolysis for ongoing DNA replication in the developing rat cerebral cortex. The protease inhibitors TLCK, TPCK, PMSF, MG-132 and PSI markedly inhibited DNA synthesis. The inhibitory effects were concentration-dependent and of early onset (within 60 min). The most selective proteasome inhibitors lactacystin and clasto-lactacystin-beta-lactone as well as the calpain inhibitor I and II had no or minimal effects on DNA synthesis. Only high concentrations of calpain inhibitor I (>or= 250 microM) and calpain inhibitor II (>or= 500 microM) gave a DNA synthesis inhibition. These results suggest that (1) ongoing DNA replication is regulated by proteolysis and (2) the proteolytic pathways involved are neither the proteasome nor the calpains.

Rapid inhibition of ongoing DNA synthesis in human glioma tissue by genistein.

The effect of genistein, a protein tyrosine kinase and topoisomerase II inhibitor, on the DNA synthesis rate was studied in 21 human glioma specimens obtained at routine craniotomies for tumor resection. Ongoing DNA synthesis rate was determined by using a method based on the generation of tissue mini-units immediately after tumor resection and short incubation time (0-120 min) with [methyl-3H]-thymidine. A 9-77% inhibition of DNA synthesis rate by 100 microM genistein was observed in 18/21 of the glioma specimens. In these cases, the average percentage of inhibition was 55+/-20% (mean+/-SD, P<0.0001, Student's t-test) and the inhibitory effect was >50% in 12/18 of the cases. In 3 cases genistein increased the DNA synthesis rate. The inhibitory effect of genistein had a short-time onset and was concentration-dependent. Additional experiments in 4 cases showed that herbimycin A had no effect on DNA synthesis rate while etoposide inhibited similarly to that of genistein. Our results suggest that the effect of genistein on DNA synthesis rate in gliomas is independent of protein kinase inhibition and probably mediated by topoisomerase II inhibition. In the RG2 model, 50 microM genistein inhibited ongoing DNA synthesis in glioma cells with little or no effect in normal tissue. The data also encourage further investigations on the therapeutic potential of genistein for gliomas.

Surgery and risk of sporadic Creutzfeldt-Jakob disease in Denmark and Sweden: registry-based case-control studies.

BACKGROUND: Epidemiologic evidence of surgical transmission of sporadic Creutzfeldt-Jakob disease (sCJD) remains controversial. METHODS: From Danish and Swedish registries we selected 167 definite and probable sCJD cases (with onset between 1987 and 2003) and 3,059 controls (835 age-, sex-, and residence-matched, and 2,224 unmatched). Independent of case/control status, surgical histories were obtained from National Hospital Discharge Registries. Surgical procedures were categorized by body system group and lag time to onset of sCJD. Exposure frequencies were compared using logistic regression. RESULTS: A history of any major surgery, conducted >/=20 years before sCJD onset, was more common in cases than both matched (OR = 2.44, 95% CI = 1.46-4.07) and unmatched controls (OR = 2.25, 95% CI = 1.48-3.44). This observation was corroborated by a linear increase in risk per surgical discharge (OR = 1.57, 95% CI = 1.13-2.18; OR = 1.50, 95% CI = 1.18-1.91). Surgery of various body systems, including peripheral vessels, digestive system and spleen, and female genital organs, was significantly associated with increased sCJD risk. CONCLUSIONS: A variety of major surgical procedures constitute a risk factor for sCJD following an incubation period of many years. A considerable number of sCJD cases may originate from health care-related accidental transmission.

Roscovitine inhibits ongoing DNA synthesis in human cervical cancer.

The effect of roscovitine, a purine analogue and cyclin dependent kinase inhibitor, on DNA synthesis rate in tissue mini-units obtained from human cervical cancers was investigated. Roscovitine (100 microM) gave a DNA synthesis rate inhibition by 61% (P<0.0001; range 23-93%) within 30 min of incubation. This inhibitory effect was concentration-dependent. The results suggest that the inhibition of tumor DNA synthesis rate is due to a direct effect on the DNA synthesis machinery via presently unknown mechanisms. In addition, the potential application of CDKs inhibitors as preventive agents is discussed.