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1.
ACS Nano ; 10(2): 2203-13, 2016 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-26766427

RESUMEN

Current studies have revealed the immune effects of graphene oxide (GO) and have utilized them as vaccine carriers and adjuvants. However, GO easily induces strong oxidative stress and inflammatory reaction at the site of injection. It is very necessary to develop an alternative adjuvant based on graphene oxide derivatives for improving immune responses and decreasing side effects. Carnosine (Car) is an outstanding and safe antioxidant. Herein, the feasibility and efficiency of ultrasmall graphene oxide decorated with carnosine as an alternative immune adjuvant were explored. OVA@GO-Car was prepared by simply mixing ovalbumin (OVA, a model antigen) with ultrasmall GO covalently modified with carnosine (GO-Car). We investigated the immunological properties of the GO-Car adjuvant in model mice. Results show that OVA@GO-Car can promote robust and durable OVA-specific antibody response, increase lymphocyte proliferation efficiency, and enhance CD4(+) T and CD8(+) T cell activation. The presence of Car in GO also probably contributes to enhancing the antigen-specific adaptive immune response through modulating the expression of some cytokines, including IL-6, CXCL1, CCL2, and CSF3. In addition, the safety of GO-Car as an adjuvant was evaluated comprehensively. No symptoms such as allergic response, inflammatory redness swelling, raised surface temperatures, physiological anomalies of blood, and remarkable weight changes were observed. Besides, after modification with carnosine, histological damages caused by GO-Car in lung, muscle, kidney, and spleen became weaken significantly. This study sufficiently suggest that GO-Car as a safe adjuvant can effectively enhance humoral and innate immune responses against antigens in vivo.


Asunto(s)
Inmunidad Adaptativa/efectos de los fármacos , Adyuvantes Inmunológicos , Carnosina , Grafito , Inmunidad Innata/efectos de los fármacos , Adyuvantes Inmunológicos/química , Adyuvantes Inmunológicos/farmacocinética , Adyuvantes Inmunológicos/farmacología , Animales , Peso Corporal/efectos de los fármacos , Carnosina/química , Carnosina/inmunología , Carnosina/farmacología , Citocinas/sangre , Grafito/química , Grafito/inmunología , Grafito/farmacología , Masculino , Ratones , Ratones Endogámicos BALB C , Tamaño de los Órganos/efectos de los fármacos , Ovalbúmina/inmunología , Distribución Tisular
2.
Med Hypotheses ; 66(5): 957-9, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16406688

RESUMEN

Ionising radiation is known one of the most effective tools in the therapy of cancer but in many thoracic cancers, the total prescribed dose of radiation that can be safely administered to the target volume is limited by the risk of complications arising in the normal lung tissue. One of the major reasons for cellular injury after radiation is the formation of reactive oxygen species (ROS). Radiation pneumonitis is an acute phase side-effect which generally subsides after a few weeks and is followed by a chronic phase characterized by inflammation and fibrosis, that can develop months or years after irradiation. Carnosine is a dipeptide composed by the amino acids beta-histidine and l-alanine. The exact biological role of carnosine is not totally understood, but several studies have demonstrated that it possesses strong and specific antioxidant properties, protects against radiation damage,and promotes wound healing. The antioxidant mechanism of carnosine is attributed to its chelating effect against metal ions, superoxide dismutase (SOD)-like activity, ROS and free radicals scavenging ability . Either its antioxidant or anti-inflammatuar properties, we propose that carnosine ameliorates irradiation-induced lung injury. Thus, supplementing cancer patients to whom applied radiation therapy with carnosine, may provide an alleviation of the symptoms due to radiation-induced lung injury. This issue warrants further studies.


Asunto(s)
Carnosina/administración & dosificación , Citocinas/inmunología , Lesión Pulmonar , Pulmón/inmunología , Neumonitis por Radiación/inmunología , Neumonitis por Radiación/prevención & control , Protección Radiológica/métodos , Carnosina/inmunología , Simulación por Computador , Humanos , Pulmón/efectos de los fármacos , Modelos Inmunológicos , Neumonitis por Radiación/etiología , Protectores contra Radiación/uso terapéutico , Neoplasias Torácicas/inmunología , Neoplasias Torácicas/radioterapia
3.
Neuroscience ; 85(2): 527-42, 1998 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9622250

RESUMEN

In the nervous system, the aminoacylhistidine dipeptide carnosine (beta-alanyl-L-histidine) has been shown to be expressed in the olfactory receptor neurons and in brain astrocytes. Using immunocytochemical techniques, we report here a dense carnosine-like immunoreactivity in the subependymal layer of the rodent forebrain. Since the subependymal layer involves two distinct compartments (astrocytic cells forming glial tubes and newly-generated cells of the rostral migratory stream, here organized to form chains contained within the glial tubes [Brannon Thomas L. et al. (1996) Glia 17, 1-14; Jancovski A. and Sotelo C. (1996) J. comp. Neurol. 258, 112-124; Lois C. et al (1996) Science 271, 978-981; Peretto P. et al. (1997) Brain Res. Bull. 42, 9-21]), we investigated in detail the cellular distribution of carnosine-like immunoreactivity in this area. By using double labelling techniques with antisera raised against carnosine and specific markers of glial tubes or chains of migrating cells, we show that carnosine-like immunoreactivity is associated with both the compartments. On the other hand, unlike markers of the rostral migratory stream, carnosine-like immunoreactivity was not observed in isolated, migrating cells located outside the subependymal layer, which spread through the olfactory bulb in a radially-oriented manner. This suggests that carnosine is transiently expressed by cells of the rostral migratory stream when moving in the tangentially-oriented part of the migration route. Moreover, we investigated the distribution of carnosine-like immunoreactivity in the postnatal rat forebrain and found that it is detectable in the subependymal layer only starting from the third postnatal week, although it is well known that the dipeptide is present in the olfactory receptor neurons since the embryonic day 16 [Biffo S. et al. (1992) J. chem Neuroanat. 5, 5162]. Taken together, these results show that camosine, other than abundantly present in astrocytes of the glial tubes, is associated to the tangential part of the rostral migratory stream.


Asunto(s)
Astrocitos/metabolismo , Carnosina/metabolismo , Movimiento Celular/fisiología , Prosencéfalo/metabolismo , Animales , Animales Recién Nacidos , Bromodesoxiuridina/metabolismo , Carnosina/inmunología , Inmunohistoquímica , Neuroglía/citología , Neuroglía/fisiología , Ratas , Ratas Wistar
5.
Brain Res Bull ; 33(4): 379-85, 1994.
Artículo en Inglés | MEDLINE | ID: mdl-8124577

RESUMEN

Serum carnosinase is a dipeptidase, which is synthesized in human brain, where it hydrolyzes homocarnosine to release free GABA. Immunohistochemical procedures were used to demonstrate the presence of this enzyme in several layers of the retina and in certain neuronal tracts of the cerebral cortex, cerebellar cortex, olfactory bulb, hippocampus, and in disseminated tracts presumably from the internal capsule, interspersed among the basal ganglia. The enzyme was also present in the epithelial cells of the choroid plexus and in corpora amylacea, which were seen in many regions of the CNS. Homocarnosine was localized either in the same tracts or in nearby neurons. For example, the Purkinje cells of the cerebellar cortex contained homocarnosine, whereas serum carnosinase was localized in adjacent neuronal projections apparently originating from outside the cerebellar cortex and having probable synaptic contact with the Purkinje cells. These findings suggest that in addition to glutamate decarboxylation, a second metabolic reaction for the formation of free GABA exists in specific neuronal tracts of the human CNS where GABA is released from homocarnosine by the action of serum carnosinase.


Asunto(s)
Sistema Nervioso Central/metabolismo , Dipeptidasas/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Animales , Especificidad de Anticuerpos , Carnosina/análogos & derivados , Carnosina/inmunología , Carnosina/metabolismo , Sistema Nervioso Central/enzimología , Sistema Nervioso Central/inmunología , Dipeptidasas/inmunología , Humanos , Técnicas para Inmunoenzimas , Inmunohistoquímica , Ratones , Ratones Endogámicos BALB C
6.
Acta Otolaryngol Suppl ; 506: 34-6, 1993.
Artículo en Inglés | MEDLINE | ID: mdl-8256598

RESUMEN

We used an anti-copper, zinc-superoxide dismutase (Cu,Zn-SOD) antibody in an immunohistochemical investigation of the distribution of SOD in the mouse olfactory mucosa. We also investigated differential staining with this antibody in comparison with an antibody specific to carnosine, a marker of mature olfactory cells. Mouse olfactory mucosa were immunostained with the ABC method with anti-SOD and anti-carnosine antibodies. When anti-SOD antibody was used, the sustentacular cells were positive in the olfactory region, whereas the olfactory cells were negative. In the respiratory region, the columnar epithelial cells were positive, whereas goblet cells were negative. The olfactory cells, olfactory vesicles and axons showed positive staining with anti-carnosine antibody, whereas the sustentacular and basal cells were negative.


Asunto(s)
Mucosa Olfatoria/enzimología , Superóxido Dismutasa/análisis , Animales , Especificidad de Anticuerpos , Carnosina/inmunología , Ensayo de Inmunoadsorción Enzimática , Inmunodifusión , Ratones
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