Estabilidad en el tiempo de relajación magnética de la solución CM-95

Introduction: the CM-95 solution constitutes a candidate for immunomodulatory medication in the therapy of cancer patients, who must comply with Good Production Practices with the corresponding qualityand stability control, according to current regulations. It was determined the stability of the CM-95solution and the leukocyte count in Balb / c mice at the time of magnetic relaxation.Methods: three pilot lots were prepared, which were subjected to shelf stability and accelerated life studies.The quality indices determined before and after the magnetic treatment were: organoleptic characteristics,pH, electrical conductivity, sodium chloride titration, preservation concentration and microbiological control. Total white blood cell count in Balb / C mice was determined before and after treatment.Results: compliance with the parameters established in accelerated conditions and solution life, with out and with magnetic treatment, was demonstrated. The utility of the container-closure system selected during the study was demonstrated. The total white blood cell count showed variations with respect to the control up to two months as an effect of the magnetic treatment.Conclusions: compliance with the established quality indices of the magnetically treated CM-95 solution was demonstrated, under accelerated conditions and useful life using both types of packaging. The activation of the immune response was evident from the treatment up to two months. It was found that the magnetic relaxation time of the solution was two months.Introducción: la solución CM-95 constituye un candidato a medicamento inmunomodulador en la terapia de pacientes con cáncer, el que debe cumplir las Buenas Prácticas de Producción con el correspondiente control de calidad y estabilidad, según las regulaciones vigentes. Se determinó la estabilidad de la solución CM-95 y el conteo de leucocitos en ratones Balb/c en el tiempo de relajación magnética. Método: se elaboraron tres lotes pilotos, los que fueron sometidos a estudios de estabilidad de vida de estante y acelerado. Los índices de calidad determinados antes y después del tratamiento magnético fueron: características organolépticas, pH, conductividad eléctrica, valoración del cloruro de sodio, concentración del preservo y control microbiológico. Se determinó el conteo de leucocitos totales en ratones Balb/C antes y después del tratamiento. Resultados: se demostró el cumplimiento de los parámetros establecidos en condiciones aceleradas y vida útil de la solución, sin y con tratamiento magnético. Se demostró la utilidad del sistema envase - cierre seleccionado durante el estudio. El conteo total de leucocitos mostró variaciones con respecto al control hasta los dos meses como efecto del tratamiento magnético. Conclusiones: se demostró el cumplimiento de los índices de calidad establecidos de la solución CM-95 tratada magnéticamente, en las condiciones aceleradas y de vida útil empleando ambos tipos de envase. Se evidenció la activación de la respuesta inmune a partir del tratamiento hasta los dos meses. Se comprobó que el tiempo de relajación magnética de la solución fue de dos meses

The Use of Static Magnetic Field on Irrigation Water and Its Effect on Mineral and Nutrient Content in <em>Solanum lycopersicum</em> L.

Solanum lycopersicum L. is a nutraceutical plant. Tomato yield and morphological features have been improved by irrigation with water treated with static magnetic field (SMF). The effect of magnetically treated water with SMF (20–200 mT) on mineral and nutritional contents in Solanum lycopersicum L. was investigated. Bromatological analyses and minerals contents were determined in tomato fruits harvested after the application of two irrigation protocols (water treated with SMF between 20 and 200 mT and water without SMF treatment as control). Fruits were selected for analysis according to a completely randomized design. Although no significant differences were observed between both groups with regard to bromatological analyses (moisture, total ash, total solids, proteins), an increasing trend was determined for these components in fruits of plants irrigated with SMF-treated water. An increase was detected for potassium (K), calcium (Ca) and cupper (Cu) concentrations in these conditions as compared to fruits of control plants. The SMF treatment of irrigation water improves the nutrient uptake and the water use efficiency in tomato. The nutraceutical value of these fruits was increase and can be considered as an important strategy for future crop production to improve food quality

Restauración de la inmunocompetencia en ratones malnutridos con la administración de un hidrolizado de microalgas

Se evaluó el efecto de la administración intraperitoneal de un hidrolizado proteico de la microalga Chlorella vulgaris en una dosis de 500 mg/kg de peso durante 6 días, como complemento de la dieta convencional en la recuperación de la inmunocompetencia de ratones Balb/c con malnutrición proteico-energética inducida experimentalmente por restricción dietética. La intervención con el hidrolizado implicó la restauración del conteo de leucocitos totales a valores similares a los del grupo control; a un incremento en los niveles de linfocitos en sangre periférica; estimuló la proliferación de las células del sistema fagocítico mononuclear y el metabolismo de los macrófagos, expresado por una mayor actividad de la enzima fosfatasa ácida lisosomal y al aumento del peso relativo y actividad hematopoyética del bazo. Estas acciones moduladoras permiten considerar al producto como un preparado inmunológicamente activo capaz de inducir un estado incrementado de resistencia no específica en el organismo.<br>The effect of the intraperitoneal administration of a protein hydrolysate of Chlorella vulgaris microalga at a dose of 500 mg/kg of weight during 6 days, as a supplement of the conventional diet in the recovery of the immunocompetence of Balb/c mice with protein-energy malnutrition experimentally induced by diet restriction, was evaluated. The intervention with the hydrolysate led to the restoration of the count of total leukocytes at values similar to those of the control group and to an increase in the levels of lymphocytes in peripheral blood. It also stimulated the proliferation of the cells from the mononuclear phagocytic system and the metabolism of the macrophages, expressed by a higher activity of the lysosomal acid phsosphatase and the rise of the relative weight and the hematopoietic activity of the spleen. These modullating actions allow to consider the product as an immunological active compound capable of inducing an increased state of nonspecific resistance in the organism

Efectos de la solución CM-95 tratada magnéticamente sobre parámetros hematológicos y bioquímicos en ratones Balb/c Effects of the magnetically treated CM-95 solution on hematologic and biochemical parameters in Balb/c mice

Se evaluaron los efectos de la solución CM-95, tratada con campo magnético estático en el intervalo de 0,01-0,16 T e inoculada una vez en un volumen de 0,2 mL en ratones Balb/c por vía intraperitoneal y la misma solución sin tratamiento magnético en animales sin inocular, para valorar su acción sobre los parámetros hematológicos y bioquímicos del metabolismo celular de estos roedores desde la fase preclínica, con vista a lo cual se procesó la sangre obtenida por sangrado total después del esquema terapéutico, así como también se calculó el número total y diferencial de leucocitos a partir del líquido sanguíneo. En el equipo autoanalizador automático Hitachi 902 se analizó el plasma extraído de cada muestra de sangre y se determinaron, entre otros elementos: proteínas totales, glucosa, creatinina, transaminasas, iones de calcio y colesterol. Se evidenció que la solución CM-95 tratada magnéticamente produjo cambios en los leucocitos sanguíneos, dados por un aumento significativo de los linfocitos con respecto a los controles, así como también en los parámetros bioquímicos, entre los cuales se modificaron los valores de glucosa, transaminasas y colesterol, pero todos dentro de límites normales para la especie. Tales resultados abren nuevas perspectivas para el posible uso de este sistema acuoso, tratado con magnetismo, en biomedicina.<br>The effects of the CM-95 solution, treated with static magnetic field in the interval of 0,01-0,16 T and inoculated once in a volume of 0,2 mL in Balb/c mice intraperitoneally and the same solution without magnetic treatment in animals without inoculation were evaluated, in order to value its action on the hematolologic and biochemical parameters of the cellular metabolism of these rodents from the preclinical phase. For this purpose, the blood obtained through total bleeding was processed after the therapeutic pattern, and the total and differential number of leukocytes was calculated using the blood. The extracted plasm of each sample of blood was examined in the automatic autoanalyzer equipment Hitachi 902 and among other elements, total proteins, glucose, creatinine, transaminases, calcium ions and cholesterol were determined. It was evidenced that the magnetically treated CM-95 solution produced changes in the blood leukocytes, given by a significant increase of the lymphocytes compared to the controls, as well as in the biochemical parameters, among which the values of glucose, transaminases and cholesterol were modified , but all within the normal limits for the species. Such results provide new perspectives for the possible use of this watery system, treated with magnetism, in biomedicina

Evaluación de la toxicidad aguda oral e irritación sobre mucosa bucal de la solución CM-95 tratada magnéticamente Oral acute toxicity and irritation on buccal mucosa evaluation of the CM-95 solution magnetically treated

La Solución CM-95 tratada magnéticamente es un producto en desarrollo que mostró propiedades inmunoestimulantes en ensayos preclínicos, característica que la hacen adecuada como candidata a inmunopotenciador. En este trabajo se evaluaron los posibles efectos tóxicos preclínicos de la Solución CM-95 tratada magnéticamente, por el método de las Clases de Toxicidad Aguda y el de irritación de la mucosa oral, adaptando las normas OECD 423 y la ISO 10993-10, respectivamente. En el método de las Clases de Toxicidad Aguda se utilizó el ensayo límite, en ratas Sprague Dawley hembras, en el cual la dosis estuvo relacionada con el nivel de inducción magnética, en este caso 0,16 T, aplicado a la Solución CM-95; y el volumen a administrar de la misma, calculado sobre la base de 2 ml de la solución por 100 g de peso corporal. La determinación de la irritación de la mucosa oral se llevó a cabo en hámster Sirios Dorados hembras mediante un ensayo a dosis repetidas durante 7 días de tratamiento en la bolsa gular derecha, con pellet de algodón impregnado con 0,5 ml de la solución tratada magnéticamente con la misma inducción. No se encontró mortalidad ni evidencias de signos tóxicos para el ensayo de toxicidad aguda, y se obtuvo un índice de irritación sobre mucosa oral de 0, por lo que la sustancia estudiada se enmarcó como "No clasificada" y "No irritante" según la metodología empleada. Estos resultados complementarán otros estudios toxicológicos para avalar la seguridad de esta Solución para su uso futuro como fármaco por vía oral.<br>CM-95 solution magnetically treated is a product which showed immunologic properties in preliminary tests, characteristic that makes it adequate as inmunopotentiator candidate. In this study the possible preclinical toxic effects of CM-95 Solution magnetically treated were evaluated, by the Acute Toxicity Class method and oral mucosa irritation test, adapting guideline OECD 423 and ISO 10993-10. In Acute Toxicity Class method was used the Limit Test, in Sprague Dawley females rats, where the dose was related to the magnetic induction level, in this case 0.16 T, applied to CM-95 Solution; and the administration volume of aqueous solution was calculated on base 2 ml per 100 g body weight. Determination of oral mucosa irritation was carried out in female golden Syrian hamsters by means of a repeated doses test during 7 days of treatment in right gular bag, with a cotton pellet impregnated with 0.5 ml of CM-95 Solution magnetically treated with the same induction. Neither mortality nor evidences of toxic signs were observed for the test of acute toxicity, and an irritation index of 0 was obtained on oral mucosa irritation test, reason why the studied substance was framed as "not classified" and "non irritating" according to the applied methodology. These results will complement other toxicological studies to guarantee the safety of this Solution for its future use as a drug by oral route

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research