Chitosan/graphene and poly(D, L-lactic-co-glycolic acid)/graphene nano-composites for nerve tissue engineering.

This study aimed at examining and comparing the fabrication process, electrical conductivity, and biological properties of Chitosan/Graphene membranes and poly(D, L-lactic-co-glycolic acid) (PLGA)/Graphene membranes. Nano-composite membranes were made using chitosan or PLGA matrix, and 0.5-1.5 wt.% graphene nano-sheets as the reinforcement material; all the membranes were fabricated through solution casting method. Fourier transform infrared spectroscopy and X-ray diffraction results indicated that the graphene had been uniformly dispersed in polymeric matrix. The membranes with 1.5 wt.% graphene appeared to have the highest value of electrical conductivity among all the examined the membranes and this growth was about 106 in comparison with neat polymers. Since the Chitosan 1.5% graphene membrane was found to have the highest proliferation after 72 hours by MTT [3-(4, 5-di-methylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] assay of PC12 cell line (p<0.05), it is promising to consider nano-composite membrane for nerve tissue engineering applications.

Combined Transplantation of Human Neuronal and Mesenchymal Stem Cells following Spinal Cord Injury.

Transplantation of human fetal neural stem cells (hNSCs) previously demonstrated significant functional recovery after spinal cord contusion in rats. Other studies indicated that human mesenchymal stem cells (hMSCs) can home to areas of damage and cross the blood-brain barrier. The purpose of this article is to determine if combined administration of mesenchymal stem cells and neuronal stem cells improves functional outcomes in rats. The study design was a randomized controlled animal trial. Female adult Long-Evans hooded rats underwent laminectomy at T10 level. Moderate spinal cord contusion at T10 level was induced by the MASCIS Impactor. Four groups were identified. The MSC + NSC group received hMSCs intravenously (IV) immediately after spinal cord injury (acute) and returned 1 week later (subacute) for injection of hNSC directly at site of injury. The MSC-only group received hMSC IV acutely and cell media subacutely. The NSC-only group received cell media IV acutely and hNSC subacutely. The control group received cell media IV acutely and subacutely. Subjects were assessed for 6 weeks using Basso, Beattie, Bresnahan Locomotor Rating Score. Twenty-four subjects were utilized, six subjects in each group. Statistically significant functional improvement was seen in the MSC + NSC group and the NSC-only group versus controls (p = 0.027, 0.042, respectively). The MSC-only group did not demonstrate a significant improvement over control (p = 0.145). Comparing the MSC + NSC group and the NSC-only group, there was no significant difference (p = 0.357). Subacute transplantation of hNSCs into contused spinal cord of rats led to significant functional recovery when injected either with or without acute IV administration of hMSCs. Neither hMSCs nor addition of hMSC to hNSC resulted in significant improvement.

Mid-term follow-up of patients with Brugada syndrome following a cardioverter defibrillator implantation: a single center experience.

BACKGROUND: Brugada syndrome is an arrhythmogenic disease characterized by an ECG pattern of ST-segment elevation in the right precordial leads and an increase risk of sudden cardiac death. Risk stratification for the life-threatening arrhythmic events in Brugada syndrome is not yet established. In the present study, we report our experience in patients with Brugada syndrome, following an ICD implantation. METHODS AND RESULTS: A total of 12 patients (11 men, 1 woman) with a mean age of 46.5+/-11.8 were studied. At diagnosis, 7 patients had syncope of unknown origin, 2 patients were asymptomatic, 2 patients were survivors of cardiac arrest, and 1 had documented clinical VT requiring direct cardioversion for termination. Age was similar between the symptomatic and asymptomatic patients (46.6+/-13 vs. 46+/-2.8, respectively). Two patients reported a family history of sudden cardiac death. In 3 patients, spontaneous coved-type ECG was found at baseline. In 9 patients, a class I antiarrhythmic drug administration unmasked the characteristic type I ECG. In 4 patients (2 symptomatic with syncope at presentation and 2 asymptomatic), who underwent PES, sustained polymorphic VT or VF was induced. VF was induced by single extrastimuli in 2 symptomatic patients (1 from RV apex and 1 from RVOT). In 2 asymptomatic patients, VF was induced by two and triple ventricular extrastimli (1 from RV apex and 1 from RVOT). None of them experienced an event during follow-up. No significant difference was found between symptomatic and asymptomatic patients (p=NS). The mean follow-up period for the entire study population was 27.83+/-11.25 months. During follow-up, 2 patients (one with prior cardiac arrest and another with syncope) had VF. Both of them had a type I ECG after provocation with a class I antiarrhythmic drug. None of them had undergone programmed ventricular stimulation. Five patients (41.7 %) had inappropriate ICD interventions during follow-up. The cause of inappropriate therapy was sinus tachycardia in 2 patients, AF in 2 patients and T wave oversensing in 1 patient. CONCLUSION: Knowledge about Brugada syndrome is steadily progressing but there are still unanswered issues dealing with the risk stratification and the management of patients.

Increased body weight in C57BL/6 female mice after exposure to ionizing radiation or 60Hz magnetic fields.

PURPOSE: The purpose of this investigation was to determine whether early treatment with ionizing radiation and/or chronic magnetic field (MF) exposure affected body weight in female mice. MATERIALS AND METHODS: Weanling C57BL/6 female mice were irradiated with four equal weekly cobalt-60 exposures (total cumulative doses: 3.0, 4.0, 5.1Gy) and/or received chronic lifetime exposure to 1.4 mT 60 Hz circularly polarized MF or ambient MF. The body weights of 2280 mice were recorded at 35 age intervals, and analysis of variance was used to compare the mean differences from baseline weights between treatment groups and sham-exposed controls. RESULTS: A highly statistically significant effect of ionizing radiation on body weight was observed at 28 age intervals (p < or = 0.001), and for MF exposure at 10 age intervals (p < or = 0.001). During the young adult growth phase, mice exposed only to MF exhibited < or =0.5 g greater weight gain relative to sham-exposed controls (p = 0.0001). The effect of ionizing radiation alone was inversely related to dose, with the largest weight increases observed in all of the irradiated groups after 9-12 months (p = 0.0001). CONCLUSIONS: Treatment with split-dose ionizing radiation at an early age and chronic exposure to a residential power frequency MF were found to produce small but significant increases in body weight.

Hematopoietic neoplasia in C57BL/6 mice exposed to split-dose ionizing radiation and circularly polarized 60 Hz magnetic fields.

This study assessed the effect of chronic exposure to a 60 Hz circularly polarized magnetic field on the occurrence of ionizing radiation-induced lymphoma and other hematopoietic neoplasia in mice. Female C57BL/6 mice received lifetime exposure to either a magnetic field flux density of 1.42 mT for 18 h/day, or an ambient magnetic field of 0.13 microT. Beginning on the first day of magnetic field exposure, 1710 mice were treated with one of three levels of split-dose Cobalt-60 gamma-radiation (cumulative 3.0, 4.0 or 5.1 Gy). The remaining 570 mice received sham irradiation treatment. Sections from 10 lymphoid tissues were evaluated histopathologically for hematopoietic neoplasia. The primary statistical analysis used the Poly3 method to compare lymphoma incidences in magnetic field (MF)-exposed and control mice. Secondary analyses used the Cox proportional hazards model to analyze incidence rates for mortality and development of specific types of neoplasia. The mortality incidence rate was increased by ionizing radiation treatment, and all neoplasms were observed sooner in irradiated mice. However, the lifetime incidence of hematopoietic neoplasia was similar in all experimental groups, including those that were not exposed to ionizing radiation. Chronic exposure to MFs did not affect the mortality incidence rates and did not change the relative incidences of hematopoietic neoplasia in mice that received the same ionizing radiation treatment, with the exception of a marginally significant reduced relative risk of 0.97 (P = 0.05) for lymphoblastic lymphoma in mice exposed to a magnetic field and treated with 5.1 Gy. Lymphomas and histiocytic sarcomas were first observed approximately 50 days sooner in mice that were exposed to magnetic fields but not ionizing radiation, although this comparison was not statistically significant and the incidence of hematopoietic neoplasia in these mice was not different from that of mice in the 0 T/0 Gy group.

Primary brain tumor incidence in mice exposed to split-dose ionizing radiation and circularly polarized 60 Hz magnetic fields.

Three sections of brain tissue from 2,657 female C57BL/6 mice were stained with hematoxylin and eosin and evaluated microscopically for proliferative lesions. Mice had been treated with either split-dose ionizing radiation (0, 3.0, 4.0 and 5.1 Gy), chronic lifetime 60 Hz circularly polarized magnetic field exposure (ambient or 14.2 G, 1.4 mT), or both, and were evaluated after natural death or euthanasia for humane reasons. Among 950 mice which were not treated with ionizing radiation, two benign spontaneous lipomatous hamartomas were observed. Seven primary brain tumors of various types not found in untreated animals were observed among the 1,707 irradiated mice. Possible promotional effects of magnetic field exposure on primary brain tumor development and incidence could not be assessed due to the low number of tumors observed.

[The characteristics of the development of the immune function in the transplanted spleen of newborn mouse pups in recipients of different ages. 2. The effect of the thymus on the functional development of the transplant]. / Osoblyvosti rozvytku imunnoï funktsiï peresadzhenoï selezinky navonarodzhenykh mysheniat retsypiientam riznoho viku. 2. Vplyv tymusa na funktsional'nyi rozvytok transplantata.

The effect of the neonatal thymus grafting or "Thymostimulin" administration on the cellularity, cell composition, immune, response to SRBC and proliferative activity of T- and B-cells in vitro were determined in neonatal spleen grafted CBA/Ca female mice of different ages. Analysis of the thymus graft effect on the T- and B-cells content in the spleen transplant from the adult and old recipients demonstrated no differences. The neonatal thymus grafting led to the essential increase of the immune response, spleen cellularity and to the diametrically opposed changing from negative to positive of the sign of the correlation coefficient between the T-cells content and the cellularity of the neonatal spleen in the old recipients. The similar effect of the neonatal thymus grafting was revealed in respect of correlative connection between content of the T-cells and PFCs in spleen grafted to the old recipients too. The "Thymostimulin" injection led only to the increase of the spleen transplant cellularity. These results suggests that the young thymic microenvironment is essential for the normal T-cells differentiation and for its normal function in the neonatal spleen transplant.

Combined chronic low dose radiation-caloric restriction: a model for regression of spontaneous mammary tumor.

PURPOSE: This study was carried out to determine whether chronic low dose radiation can act alone or in synergy with restricted diet in down-regulating spontaneously occurring mammary tumor in tumor-susceptible female C3H/He mice and whether immune cells are involved. METHODS AND MATERIALS: At 7 months of age, one-half of the experimental mice were maintained on an ad lib diet, and the other half was adapted over a period of 1 month to a diet of 70% of the daily amount of food consumed by the ad lib-fed mice. The food of the restricted diet was enriched such that the vitamin and mineral intake was the same for both groups. Half of the mice in each group was then subjected to chronic low dose radiation (0.04 Gy per exposure from a 60Co source, 3 x-per-week for 4 weeks) and the other half was sham irradiated. The 70% calorically restricted diet was maintained throughout the study. RESULTS: Chronic low dose radiation alone was ineffective in down-regulating spontaneous mammary tumor, unlike caloric restriction. However, chronic low dose radiation when combined with caloric restriction promoted regression of mammary tumors, which were infiltrated with massive numbers of CD8+ T cells. These phenomena were not seen in mice subjected to caloric restriction alone. CONCLUSION: Combined chronic low dose radiation-caloric restriction appears to be a useful model for promoting spontaneous mammary tumor regression.

[Effect of splenectomy on the development of neonatal lymphoid organs transplanted to animals of varying age]. / Vliianie splenéktomii na razvitie limfoidnykh organov novorozhdennykh, peresazhennykh zhivotnym raznogo vozrasta.

The effect of splenectomy on the development of newborn thymus and spleen grafted under the kidney capsule of young and old mice has been investigated. Preliminary splenectomy is shown to increase cell counts in grafted spleen that is more conspicuous in young recipients as compared with old ones. This result suggests a decrease with age in the inhibitory effect of the host spleen on the maturation of spleen grafted from newborn donor. Combined transplantation of newborn thymus and spleen has revealed a decrease of cell counts in the donor spleen grafted to the young splenectomized recipients and, on the contrary, increase of this parameter in old ones. Immune response in donor spleen with combined transplantation of the thymus to the old splenectomized recipients is much higher as compared with the same parameter in recipient without splenectomy. It is concluded that partial destruction of the old immune system is essential for its correction.

[Influence of the recipient's age on the effect of transplanting lymphoid organs from newborn donors]. / Vliianie vozrasta retsipienta na éffekt transplantatsii limfoidnykh organov novorozhdennykh donorov.

The development of immunological capacity of newborn thymus and spleen grafted under the kidney capsule of different-age recipients was investigated. The grafts functions appear to depend strongly upon the macroenvironment of the organism where their development occurs. Therefore+ the favourable influence of young environmental factors, gradually decreasing with the recipient age to become immunosuppressive in old animals is obtained. These data indicate a predominant significance of the macroenvironmental factors both in maturation of the immune system and its alteration during aging.

[Effects of the age of the recipient on the outcome of transplantation of lymphoid organs from newborn donors]. / Vliianie vozrasta retsipienta na éffekt transplantatsii limfoidnykh organov novorozhdennykh donorov.

The comparison of developmental capacities of simultaneously grafted thymus and spleen taken from newborn CBA mice in young and old macroenvironment was attempted using the method of heterotopic chimera construction. The perceptible augmentation of immune response in both host and donor spleens was obtained in case of transplantation into the young animals, and completely opposite effect, i. e. well-marked immunosuppression in case of old recipients. Preliminary removal of host spleen results in abolition of this suppressive effect in old animals. Moreover, immune response in donor spleen following thymus transplantation into the old splenectomized recipients was significantly higher compared to the same one without additional thymus graft. Taken together, these findings indicate that despite the existence of some potency for autonomous development the eventual effect of neonatal lymphoid organs maturation strongly depends upon the age of system in which this maturation does take place.

[The role of arachidonic acid derivatives in the system of immunity and its changes in aging]. / Rol' proizvodnykh arakhidonovoi kisloty v sisteme immuniteta i ee izmeneniiakh pri starenii.

The most eminent accessible results ot few last decades concerning the significance of the arachidonic acid metabolites (AAM) for the cell function are summarized in the review. The importance of such substances for the immune system is also emphasized. The AAM (especially PGE2) implication in the process of non-specific T cell induction is discussed in detail.

Effect of thymus grafts of various ages on the immune system formation in CBA mice.

An attempt has been made to govern the development of immunological capability in CBA mice by means of transplantation at an early postnatal period of thymus from donors of various ages. The results have shown that in thymectomized animals, apart from a well known gradual decline with the donor's age in restorative functions of the transplanted thymus, there was at the age of 22 months a phase of inhibitory influence on the recipient's immune system. In intact animals, transplantation of the thymus from a 5-day-old donor caused a decrease and that from a 22-month-old donor caused an increase in the development of the capacity for immune response. Taken together, our findings indicate an active role of the thymus both in the formation of the immune system and in its alteration with aging.

[Effect of the transplantation of heterochronic thymus on the development of immunological reactivity in CBA mice. 2. Transplantation to intact animals]. / Vliianie peresadki geterokhronnogo timusa na stanovlenie immunologicheskoi reaktivnosti u myshei CBA. 2. Transplantatsiia intaktnym zhivotnym.

The effect of transplantation of thymus from donors of different age on the immune system development was studied in the newborn CBA mice. The thymuses of 22 month and 5 day old donors were shown to exert different effects: accelerated (early attainment of the plateau) and decelerated (late attainment of the peak) maturation of the immune system in the recipients. This fact is discussed with respect to interaction of transplanted and host thymuses.