Protective effect of liposomal formulation of tuftsin (a naturally occurring tetrapeptide) against cyclophosphamide-induced genotoxicity and oxidative stress in mice.

Tuftsin, a naturally occurring tetrapeptide with a sequence Thr-Lys-Pro-Arg was evaluated for its in vivo protective effect against cyclophosphamide-induced genotoxicity and oxidative stress in Swiss albino mice. The anticancer drug cyclophosphamide (CP) was administered intra-peritonially to induce mutagenic effect. The drug treatment caused significant increase in chromosomal aberrations, formation of micronucleated polychromatic erythrocytes (MNPCE's), as well as oxidative stress and decrease in lipid peroxidation in liver of the animals. The pretreatment with tuftsin abolished such effects in dose-dependent manner and also increased mitotic index in the experimental animals. Results of the present study validated chemo-preventive properties of tuftsin against CP-induced chromosomal mutations and cellular injury of liver by oxidative stress.

Avaliação do efeito da esplenectomia e auto-implante esplênico sobre algumas funções de monócitos em crianças com esquistossomose mansônica / Evaluation of the effect of splenectomy with autologous spleen tissue implantation in some monocyte functions in children with hepatosplenic schistosomiasis mansoni

Investigamos em portadores de esquistossomose hepatoesplênica após esplenectomia com ou sem auto-implante esplênico: índice de aderência, produção de superóxido (SP) e de TNF-alfa em monócitos, tratados ou não com tuftsina. Avaliamos três grupos: voluntários sadios CG (grupo controle) (n=12); esplenectomizados com auto-implante AG (n=18) e esplenectomizados sem auto-implante WAG (n=9). índice de aderência e TNF-alfa não diferiram entre os grupos. SP foi semelhante em CG e AG na 1ª hora após estimulação celular. SP foi maior em todos intervalos de tempo nos grupos CG e AG, comparados ao WAG. O tratamento com tuftsina recuperou o padrão de normalidade de SP em AG, com aumento da 1ª para a 2ª hora nos níveis do CG. O tratamento com tuftsina não alterou SP em WAG, permanecendo reduzida em todos intervalos. O auto-implante esplênico parece recuperar e manter os parâmetros imunológicos avaliados, que têm participação importante na resposta do hospedeiro às infecções.

Pancreatectomía distal con conservación de bazo: aspectos técnicos y análisis de nuestra casuística / Distal pancreatectomy with spleen preservation: technique and the outcomes of our experience

Antecedentes: Clásicamente la esplenectomía ha formado parte de la pancreatectomía distal. El reconocimiento de la importancia de las funciones del bazo ha motivado el interés en la conservación del mismo. La pancreatectomía distal con conservación de bazo fue descripta por primera vez en 1943. Con la excepción de algunos casos reportados en la literatura internacional, no se ha implementado rutinariamente en cirugía electiva. En los últimos años, se observó un interés en su utilización para el tratamiento de lesiones benignas y de bajo grado de malignidad y se desarrolló la resección por vía laparoscópica. Objetivo: Revisión de la evolución técnica y de nuestra casuística. Población: Intentamos conservar el bazo en 25 pacientes con lesiones benignas entre 1993 y 2001. Método: Se realizó pancreatectomía distal con conservación de bazo y vasos esplénicos. El último caso se realizó por vía laparoscópica. Resultados: La preservación del bazo fue posible en 24 de los 25 pacientes y en 23 pudieron preservarse los vasos esplénicos. El tiempo operatorio promedio fue 195 minutos. Cinco pacientes presentaron complicaciones postoperatorias (21,7 por ciento). No hemos observado isquemia ni absceso de bazo en ésta serie. La estadía hospitalaria promedio fue de 8,3 días. El seguimiento postoperatorio varió entre 5 y 80 meses (promedio 40 meses), sin detectarse alteraciones hematológicas por asplenia. Un paciente desarrolló diabetes insulino-dependiente 6 años luego de la operación (4 por ciento) y no se observó ningún caso de alteración de la función exocrina del páncreas. Conclusiones: La pancreatectomía distal con conservación de bazo es una operación segura y eficaz. La preservación de los vasos esplénicos evita el desarrollo de abscesos del bazo. La sección pancreática previa a la disección retrógrada, descripta en éste traabajo, facilita la preservación de los vasos esplénicos. Esta técnica es reproducible mediante el abordaje laparoscópico

Autotransplant of spleen tissue in children with schistosomiasis: evaluation of splenic function after splenosis

Autotransplantation of spleen tissue has been done, in the past ten years, in children with schistosomiasis mansoni with bleeding varices. The purposes of this investigation were: (1) to study the morphology and function of the remnant spleen tissue; (2) to quantify the production of tuftsin; and (3) to assess the immune response to pneomococcal vaccine of these patients. Twenty three children, who underwent splenectomy and autologous implantation of spleen tissue into the greater omentum were included in this investigation. The average postoperative follow-up is five years. Splenosis was proved by colloid liver-spleen scans. Search for Howell-Jolly bodies assessed the filtration function. Tuftsin and the titer of pneumococcal antibodies were quantified by ELISA. Splenosis was evident in all children; however, it was insufficient in two. Howell-Jolly bodies were found only in these two patients. The mean tuftsin serum concentration (335.0 ± 29.8 ng/ml) was inside the normal range. The immune response to pneumococcal vaccination was adequate in 15 patients; intermediate in four; and inadequate in four. From the results the following conclusions can be drawn: splenosis was efficient in maintaining the filtration splenic function in more than 90 percent and produced tuftsin inside the range of normality. It also provided the immunologic splenic response to pneumococcal vaccination in 65 percent of the patients of this series

Theoretical study of conformational flexibility of tuftsin in vacuum and in aqueous environment.

Conformational flexibility of tuftsin molecule is studied using all-atom based atom-atom potential and systematic search, simulated annealing molecular dynamics (SAMD) and molecular dynamics (MD) techniques. Latter was carried out for 650 pico seconds (ps) using AMBER 4.0 with explicit water in TIP3P model. Number of inter-atomic distances and torsional angles were monitored during SAMD and MD simulation. We found that tuftsin molecule, irrespective of any starting conformation, assumes highly folded structure with strong electrostatic interaction between Lys-2 NH3 and Arg-4 carboxylic group and weak hydrogen bond between Lys-2 CO and Arg-4 NH atoms. It had distorted but stable conformation close to inverse gamma turn.

Single-step bulk purification of synthetic tetrapeptide tuftsin by high performance liquid chromatography.

A protocol on reversed phase high performance liquid chromatogrpahy (RP-HPLC) using water-acetonitrile gradients under lesser stringent conditions, has been devised to obtain highly purified tuftsin in bulk amount. The protocol was also tested for two different preparations of tuftsin to yield identical quality of peptide.

Immunological study of autotransplantation and partial splenectomy after traumatic rupture of the spleen

Due to the settled risk of the so called over-whelming post splenectomy Infection reported in both children and adults, which may represent a life-long risk and caused mainly by bacteria, we aimed to establish a spleen-preserving operative procedure which could be easily done when partial splenectomy is not possible, and we aim to focus light on the importance to preserve the spleen as an immnnological valuable organ. The levels of humeral immunity, mainly IgM was found to reduce after total splenectomy while its mean value increased after partial splenectomy or autotransplantation. Changes of IgG were not marked in asplenics in both children and adults [2.086 dropped to 1.700 gm/L and 2.063 to 1.675]. The phagocytic activity also decreased in asplenic subjects very significantly [76.5 to 57.7 for children and 79.2 to 63.2 for adults]. Tuftsin value was reduced in asplenics [2.17 to 2.11 mg/ml]. All these parameters were not affected in eusplenic operated subjects

Efecto in vitro de la tuftsina (L-prolil-L-arginina) en la capacidad oxidativa de los polimorfonucleares en niños recién nacidos pequeños para su edad gestacional / Tuftsin (L-prolil-L-arginina) has the function of activating cellular macrophages and polymorphonucleras in newborns

Se comunican los resultados de un trabajo realizado para determinar el efecto de la tuftsina sintética en la capacidad oxidativa de células polimorfonucleares de niños recién nacidos pequeños para su edad gestacional, ya que se ha demostrado que está disminuida la actividad fagocítica de macrófagos y polimorfonucleares (PMNs) comparada con las células de niños con peso adecuado para su edad gestacional. En los resultados se observó un efecto de estimulación de la capacidad oxidativa de los PMNs con tuftsina sintética a través de incrementar la reducción de nitroazul de tetrazolio, lo que sugiere que la baja capacidad oxidativa de las células de recién nacidos pequeños para su edad gestacional no se relaciona con un defecto intrínseco celular

Effect of splenectomy and tuftsin on leukocyte functions in hepatosplenic schistosomiasis

This study concerning the effect of splenectomy, role of tuftsin, as a phagocytosis promoting agent, on the polymorphunclear leucocyte functions and its effect on the immune mechanism in hepatosplenic schistosomiasis. It was carried out on fifteen normal controls group, fifteen cases with splenomeglic bilharizal hepatic fibrosis and other seven cases of bilharzial splenomegaly that underwent splencetomy 1.5-7 years before being subjected to this study. The methods applied in this work, comprised the estimation of neutrophil chemotaxis, phagocytosis and intracellular killing of candida albicans with and without tuftsin in the different groups. Statistical analysis of the data obtained without tuftsin, revealed a depression of migratory, phagocytosis and candidacidal activities of PMN leucocytes in splenomegatic schistosomiasis. These functions were remarkably improved after splencetomy denoting that there might be a variable degree of immune depression exerted by the enlarged spleen. This was explained by a defective synthesis of tuftsin necessary for leucocyte functions, beside its depressant effect on normal neutrophil production. Analysis of the data obtained after the addition of tuftsin denotes that, tuftsin improves migratory, phagocytosis and candidacidal activities of PMN leucocytes in all the groups. This means that tuftsin is an essential factor that improves the leucocyte functions