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In the recent years a special attention has been given to a major health concern namely to male infertility, defined as the inability to conceive after 12 months of regular unprotected sexual intercourse, taken into account the statistics that highlight that sperm counts have dropped by 50-60% in recent decades. According to the WHO, infertility affects approximately 9% of couples globally, and the male factor is believed to be present in roughly 50% of cases, with exclusive responsibility in 30%. The aim of this article is to present an evidence-based approach for diagnosing male infertility that includes finding new solutions for diagnosis and critical outcomes, retrieving up-to-date studies and existing guidelines. The diverse factors that induce male infertility generated in a vast amount of data that needed to be analyzed by a clinician before a decision could be made for each individual. Modern medicine faces numerous obstacles as a result of the massive amount of data generated by the molecular biology discipline. To address complex clinical problems, vast data must be collected, analyzed, and used, which can be very challenging. The use of artificial intelligence (AI) methods to create a decision support system can help predict the diagnosis and guide treatment for infertile men, based on analysis of different data as environmental and lifestyle, clinical (sperm count, morphology, hormone testing, karyotype, etc.), and "omics" bigdata. Ultimately, the development of AI algorithms will assist clinicians in formulating diagnosis, making treatment decisions, and predicting outcomes for assisted reproduction techniques.
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Infertilidad Masculina , Infertilidad , Inteligencia Artificial , Humanos , Infertilidad/terapia , Infertilidad Masculina/diagnóstico , Infertilidad Masculina/genética , Masculino , Técnicas Reproductivas Asistidas , SemenRESUMEN
Context: Obesity is a complex and heterogeneous disorder with multiple phenotypes described. Although metabolomic biomarkers of obesity have been extensively studied, biomarkers of obesity phenotypes and differences between these phenotypes and normal-weight (NW) persons have been less investigated. Objective: The objective of this cross-sectional analysis was to investigate serum amino acids (AA) as markers of metabolic alterations in obesity phenotypes and NW. Design: Cross-sectional. Subjects and Methods: By targeted metabolomics we analyzed serum samples of 70 women using ultrahigh-performance liquid chromatography/mass spectrometry. Participants were divided into 3 groups: NW, metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). Results: Five AAs were significantly different between study groups: cysteine, methionine, asparagine, glutamine, and lysine (p-value <0.05 and variable importance in the projection >1). Cysteine increased linearly with metabolic unwellness from NW to MUHO. Lysine and glutamine were significantly higher, and asparagine was significantly lower in NW and MHO than in MUHO. Conclusions: By trend and group analysis we identified specific changes in serum AAs along with the progression of metabolically unwellness.
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Celiac disease (CD) is an autoimmune condition that occurs in genetically predisposed people where the ingestion of gluten produces damage in the small intestine. The treatment accepted until now is a strict gluten free diet. This implies the need for novel or adjuvant treatments, in addition to the standard of care. The present study aimed to assess the effect of gold nanoparticles phytosynthesized with Cornus mas extract (AuCM) compared to Cornus mas extract (CM) and luteolin (LT) on Caco-2 cells, exposed or not to gliadin. Ultraviolet-visible spectroscopy and transmission electron microscopy were used for the characterization of AuCM. Measured cellular outcomes included oxidative stress markers (malondialdehyde level, catalase and superoxide dismutase activities), inflammatory response and cellular signaling and transcription factors involved in apoptosis (NFκB, pNFκB, NOS2, TNF-α, TRAIL, Bax, Bcl-2, p53). The internalization of gold nanoparticles in cells was evidenced by transmission electron microscopy (TEM). The gliadin administration induced oxidative stress, improved the activity of antioxidants enzymes, increased NOS2 and NFκB expressions and reduced pNFκB/NFκB ratio. In addition, gliadin enhanced TRAIL and Bcl-2 levels and reduced p53 expression in Caco-2 cells. The pretreatment with AuCM, CM extract and LT diminished oxidative stress and reduced NOS2 activity. AuCM and CM treatment amplified the expression of p53 and pNFκB/NFκB ratio and diminished Bcl-2, NFκB and pNFκB, especially AuCM. The results obtained confirmed that AuCM mitigate some of gliadin effects on Caco-2 cells through modulation of oxidative stress and inflammation.
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Neoplasias del Colon/tratamiento farmacológico , Cornus/química , Gliadina/toxicidad , Oro/química , Nanopartículas del Metal/administración & dosificación , Extractos Vegetales/farmacología , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Células CACO-2 , Neoplasias del Colon/inducido químicamente , Neoplasias del Colon/patología , Humanos , Inflamación/tratamiento farmacológico , Nanopartículas del Metal/química , Estrés Oxidativo/efectos de los fármacosRESUMEN
In E-Poster Sessions of the published abstract, the authors' affiliations as well as the abstract text were incorrectly presented. The correct abstract and the author's affiliations are shown in full in this article.
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BACKGROUND: Exposure to high altitude in hypobaric hypoxia (HH) is considered to be a physiological oxidative/nitrosative stress. Quercetin (Que) is an effective antioxidant and free radical scavenger against oxidative/nitrosative stress. AIMS: The aim of this study was to investigate the cardioprotective effects of Que in animals exposed to intermittent HH (IHH) and therefore exposed to oxidative/nitrosative stress. MATERIALS AND METHODS: Wistar albino male rats were exposed to short-term (2 days) or long-term (4 weeks; 5 days/week) IHH in a hypobaric chamber (5,500 m, 8 h/day, 380 mmHg, 12% O2, and 88% N2). Half of the animals received natural antioxidant Que (body weight: 30 mg/kg) daily before each IHH exposure and the remaining rats received vehicle (carboxymethylcellulose solution). Control rats were kept under normobaric normoxia (Nx) and treated in a corresponding manner. One day after the last exposure to IHH, we measured the cardiac hypoxia-induced oxidative/nitrosative stress biomarkers: the malondialdehyde (MDA) level and protein carbonyl (PC) content, the activity of some antioxidant enzymes [superoxide dismutase (SOD) and catalase (CAT)], the nitrite plus nitrate (NOx) production, and the inducible nitric oxide synthase (iNOS) protein expression. RESULTS: Heart tissue MDA and PC levels, NOx level, and iNOS expression of IHH-exposed rats had increased, and SOD and CAT activities had decreased compared with those of the Nx-exposed rats (control groups). MDA, CP, NOx, and iNOS levels had decreased in Que-treated IHH-exposed rats compared with IHH-exposed rats (control groups). However, Que administration increased SOD and CAT activities of the heart tissue in the IHH-exposed rats. CONCLUSION: HH exposure increases oxidative/nitrosative stress in heart tissue and Que is an effective cardioprotective agent, which further supports the oxidative cardiac dysfunction induced by hypoxia.
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Antioxidantes/farmacología , Corazón/efectos de los fármacos , Hipoxia/fisiopatología , Estrés Nitrosativo/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Quercetina/farmacología , Altitud , Animales , Masculino , Ratas , Ratas WistarRESUMEN
Background To investigate the protective effects of Quercetin administration associated with chronic moderate exercise (training) on oxidative stress in the liver in streptozotocin-induced diabetic rats. Methods Diabetic rats that performed exercise training were subjected to a swimming training program (1 hour/day, 5 days/week, 4 weeks). The diabetic rats received natural antioxidant, Quercetin (20 mg/kg body weight/day) for 4 weeks. At the end of the study, all animals were sacrificed and liver samples were collected for estimation: some oxidative stress markers (malondialdehyde, MDA and protein carbonyls groups, PC), the activity of antioxidant enzymes (superoxide dismutase, SOD and catalase, CAT), reduced glutathione (GSH) level and reduced (GSH) and oxidized (GSSG) glutathione ratio. Results Diabetic rats submitted to exercise training showed significantly increased the oxidative stress markers (MDA and PC) and a reduction of antioxidant enzyme (SOD and CAT) activity, GSH level and GSH/ GSSG ratio in hepatic tissues. A decrease in the levels of oxidative stress markers associated with elevated activity of antioxidant enzymes, the GSH level and GSH/GSSG ratio in the hepatic tissue were observed in Quercetin-treated diabetic trained rats. Conclusions These findings suggest that Quercetin administration in association with chronic moderate exercise exerts a protective effect in diabetes by attenuating hyperglycemia-mediated oxidative stress in hepatic tissue.
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Citoprotección/efectos de los fármacos , Diabetes Mellitus Experimental/metabolismo , Hígado/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Condicionamiento Físico Animal/fisiología , Quercetina/farmacología , Animales , Antioxidantes/metabolismo , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/patología , Peroxidación de Lípido/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Malondialdehído/metabolismo , Condicionamiento Físico Animal/métodos , Ratas , Ratas Wistar , EstreptozocinaRESUMEN
The study aims to investigate the mechanisms involved in the in vitro effect of UVB on endothelial vascular cells (HUVECs) pretreated with a photochemopreventive agent, the Calluna vulgaris (Cv) extract. Two concentrations of Cv, below the limit of cytotoxicity IC50 (2.5 and 7.5 µg GAE/ml) and two doses of UVB (50 and 100 mJ/cm(2)) were used. Oxidative stress parameters were quantified at 1 h and 24 h after irradiation and apoptosis, DNA damage and the induction/activation of NF-κB were evaluated at 24 h. UVB exposure led to the formation of lipid peroxides in a dose dependent manner (p<0.001), induced apoptosis, increased the γ-H2AX levels and the activation of NF-κB. Pretreatment with 2.5 µg GAE/ml Cv improved the antioxidant defense, protected against DNA lesions and was able to decrease cellular death at low dose of irradiation. 7.5 µg GAE/ml Cv was prooxidant, favored the formation of DNA lesions, amplified the NF-κB activation UVB-induced (p<0.01) and led to high levels of cellular death. Both doses of Cv inhibited caspase-3 activation. The modulatory effect of Cv extract on endothelial cells exposed to UVB depend on the concentration of Cv used. This study provides insides into the mechanisms triggered by UVB and antioxidants on skin endothelial cells.
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Anticarcinógenos/farmacología , Antioxidantes/farmacología , Calluna , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Extractos Vegetales/farmacología , Rayos Ultravioleta/efectos adversos , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Daño del ADN/efectos de los fármacos , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Histonas/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de la radiación , Humanos , Peroxidación de Lípido/efectos de los fármacos , Malondialdehído/metabolismo , FN-kappa B/metabolismo , Componentes Aéreos de las PlantasRESUMEN
Aluminum (Al) and indium (In) have embryotoxic, neurotoxic and genotoxic effects, oxidative stress being one of the possible mechanisms involved in their cytotoxicity. We have recently demonstrated that indium intraperitoneal (ip) administration induced histological disorganization of testicular tissue. In the present research we aimed at investigating the effect of Al and In ip administration on systemic and testicular oxidative stress status. Studies were performed on Wistar rats ip injected with Al, In or physiological solution for two weeks. Our results showed that In significantly decreased the absolute weight of testicles. Measurements of lactate dehydrogenase (LDH) and paraoxonase (PON) activities showed that In induced a significant augmentation in the first parameter but no changes were observed in the second. Both Al and In caused oxidative stress in testicles by increasing malondialdehyde (MDA) and protein carbonyls (PC) production. Concomitantly, thiol group (-SH) and glutathione (GSH) level were enhanced in the testicles. In the blood, while concentrations of MDA was not changed, those of GSH was significantly decreased in the Al and In groups. Our results indicated that Al and In cause oxidative stress both in blood and testicles but In has cytotoxic effect as well as negative impact on testicle weights. These findings could explain the testicular histological alterations previously described after In ip administration.
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Compuestos de Aluminio/toxicidad , Indio/toxicidad , Nitratos/toxicidad , Estrés Oxidativo/efectos de los fármacos , Testículo/efectos de los fármacos , Compuestos de Aluminio/administración & dosificación , Animales , Arildialquilfosfatasa/sangre , Biomarcadores/sangre , Glutatión/sangre , Indio/administración & dosificación , Inyecciones Intraperitoneales , L-Lactato Deshidrogenasa/sangre , Masculino , Malondialdehído/sangre , Nitratos/administración & dosificación , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Tamaño de los Órganos , Carbonilación Proteica/efectos de los fármacos , Ratas , Ratas Wistar , Testículo/metabolismo , Testículo/patologíaRESUMEN
In the early stages of cholestasis, a plethora of mechanisms are considered to contribute to the liver injury: oxidative stress, inflammation, cholangiocytes proliferation and fibrosis. Our study aims to investigate the effects of different doses of rosuvastatin (Ro) on experimental bile duct ligation-induced cholestasis. 40 female Wistar rats were randomly divided into 4 groups (n=10): Sham group (laparotomy); BDL group (subjected to bile duct ligation); BDL group treated with Ro (5 mg/bw daily); BDL group treated with Ro (10 mg/bw daily). After 6 days of treatment, in the day 7 after BDL, the animals were sacrificed and we explored hepato-cytolysis, the seric parameters for cholestasis and oxidative stress in plasma, liver, brain and kidneys. Proliferation was investigated by expression of proliferating cell nuclear antigen (PCNA), while inflammation by liver histology, TNFR2 expression and NF-κB induction and activation. To assess fibrosis, we performed Tricrom-Masson staining, transforming growth factor beta-1 (TGF-ß1) expression, and for myofibroblast activation, we analyzed α-SMA expression. The administration of Ro in early stages of cholestasis proved to have a beneficial effect by decreasing α-SMA. Ro didn't exert systemic oxidative stress effects, but increased hepatocytolysis, oxidative stress and inflammation in the liver and sustained increased levels of pro-fibrotic cytokine TGF-ß1 as well as the number of proliferating cells in ducts and parenchyma. Ro inhibited the induction and the activation of NF-κB, which could be considered a beneficial effect. Further studies must be carried out in order to clearly investigate the balance between risks and benefits for Ro administration in early stages of cholestasis.
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Colestasis/metabolismo , Fluorobencenos/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Hígado/efectos de los fármacos , Pirimidinas/farmacología , Sulfonamidas/farmacología , Actinas/metabolismo , Alanina Transaminasa/metabolismo , Animales , Aspartato Aminotransferasas/metabolismo , Conductos Biliares , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Colestasis/patología , Modelos Animales de Enfermedad , Femenino , Riñón/efectos de los fármacos , Riñón/metabolismo , Ligadura , Hígado/metabolismo , Hígado/patología , Malondialdehído/metabolismo , FN-kappa B/antagonistas & inhibidores , FN-kappa B/metabolismo , Estrés Oxidativo , Antígeno Nuclear de Célula en Proliferación/metabolismo , Carbonilación Proteica/efectos de los fármacos , Ratas , Ratas Wistar , Receptores Tipo II del Factor de Necrosis Tumoral/metabolismo , Rosuvastatina Cálcica , Factor de Crecimiento Transformador beta1/metabolismo , gamma-Glutamiltransferasa/metabolismoRESUMEN
Photochemoprevention with natural products represents a new concept in the attempt to reduce the occurrence of skin cancer. However, the molecular mechanisms caused by ultraviolet light exposure remain still unclear. The aim of the study was to assess the mechanisms involved in the action of a Calluna vulgaris (Cv) extract, administered in single or multiple doses (10 consecutive days), on UVB-induced skin damage in SKH-1 hairless mice. The extract was topically applied 30 min before each UVB exposure in two doses (2.5 and 4 mg total polyphenolic content/40 µl/cm(2)). At 24 hours after the last treatment, total mitogen-activated protein kinase (p44/42MAPkinase, ERK 1/2), nuclear factor-κB (phospho-NF-κB p65), matrix metalloproteinases (MMP-2, MMP-9) and metalloproteinase inhibitor 1 (TIMP-1) levels were measured in skin using enzyme-linked immunosorbent assay (ELISA). MMP-2 and -9 activities were additionally evaluated by zymography. One topical application of Cv extract reduced the secretion (p<0.004) and inhibited MMP-9 activity UVB-mediated (54% inhibition) via inhibition of NF-κB activation (68% inhibition). In multiple UVB exposures, both doses of Cv extract induced the increase of ERK 1/2 level in correlation with activation of NF-κB and reduced the secretion (p<0.04) and activation of MMP-9 (62% inhibition). Pretreatment with Cv diminished the MMP-2 protein secretion only in one dose UVB-irradiated group (p<0.0001) and decreased TIMP-1 level (p<0.001). These results demonstrated the dual behavior of Cv extract in skin protection against single versus multiple doses of UVB irradiation.
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Calluna , Extractos Vegetales/administración & dosificación , Sustancias Protectoras/administración & dosificación , Piel/efectos de los fármacos , Rayos Ultravioleta/efectos adversos , Administración Tópica , Animales , Eritema/etiología , Eritema/metabolismo , Eritema/patología , Femenino , Hiperplasia/etiología , Hiperplasia/metabolismo , Hiperplasia/patología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Pelados , FN-kappa B/metabolismo , Componentes Aéreos de las Plantas , Piel/metabolismo , Piel/patología , Piel/efectos de la radiación , Inhibidor Tisular de Metaloproteinasa-1/metabolismoRESUMEN
UNLABELLED: Inflammation and oxidative stress are important pathways in the development of liver fibrosis following biliary obstruction. AIM: To evaluate the effects of low dose dexamethasone and chitosan, a natural compound with no side-effects, on liver damage caused by bile duct ligation in rats. MATERIALS AND METHODS: Fifty female Wistar rats, randomly and equally divided in 5 groups: I (SHAM) underwent only laparotomy, II (BDL) with bile duct ligation, III (DEX) 0.125 mg/kg dexamethasone i.m. daily, IV (CS) 1 mg/kg chitosan by gavage and group V (DEX+CS), both substances. After six days, the following parameters were assessed from liver homogenates: malondialdehyde (MDA), protein carbonyls (PC), reduced glutathione (GSH), total SH groupings, nitric oxide (NO), and from plasma: MDA, γ-glutamyltranspeptidase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TB). A histopathological examination was performed using some of the elements of the Knodell Histological Activity Index. RESULTS: BDL significantly increases the levels of MDA, liver enzymes, and the necro-inflammatory score compared to the sham group and it decreases the antioxidant capacity. DEX protects against lipid peroxidation and improves the antioxidant capacity, but it is not able to protect the hepatocytes. Chitosan significantly decreases (p<0.05) the levels of MDA (0.07±0.01 vs 0.10±0.01 nmoles/mg protein BDL group, p=0.027) and also ALT, TB, GGT and reduces liver necrosis and inflammation (2.75±0.95 vs 1±0, p<0.05). Both CS and DEX reduce the level of NO significantly. CONCLUSION: BDL induces severe oxidative stress damage after six days already. Chitosan proved very efficient in protecting the hepatocytes against oxidative stress, a fact supported by the histological findings.
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Quitosano/farmacología , Colestasis Extrahepática/tratamiento farmacológico , Colestasis Extrahepática/metabolismo , Dexametasona/farmacología , Animales , Anticolesterolemiantes/farmacología , Antioxidantes/farmacología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Glucocorticoides/farmacología , Glutatión/metabolismo , Ligadura , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
Solar ultraviolet radiation (UV) is a major cause of non-melanoma skin cancer in humans. Photochemoprevention with natural products represents a simple but very effective strategy in the management of cutaneous neoplasia. The study investigated the protective activity of Calluna vulgaris (Cv) and red grape seeds (Vitis vinifera L, Burgund Mare variety) (BM) extracts in vivo on UVB-induced deleterious effects in SKH-1 mice skin. Forty SKH-1 mice were randomly divided into 4 groups (n=10): control, UVB irradiated, Cv + UVB irradiated, BM+UVB irradiated. Both extracts were applied topically on the skin in a dose of 4 mg/40 µl/cm(2) before UVB exposure - single dose. The effects were evaluated in skin 24 hours after irradiation through the presence of cyclobutane pyrimidine dimers (CPDs) and sunburn cells, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6 levels. The antioxidant activity of BM extract was higher than those of Cv extract as determined using stable free radical DPPH assay and ABTS test. One single dose of UVB generated formation of CPDs (p<0.0001) and sunburn cells (p<0.0002) and increased the cytokine levels in skin (p<0.0001). Twenty hours following irradiation BM extract inhibited UVB-induced sunburn cells (p<0.02) and CPDs formation (p<0.0001). Pretreatment with Cv and BM extracts resulted in significantly reduced levels of IL-6 and TNF-α compared with UVB alone (p<0.0001). Our results suggest that BM extracts might be a potential candidate in preventing the damages induced by UV in skin.
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Calluna , Fitoterapia , Extractos Vegetales/farmacología , Neoplasias Cutáneas/prevención & control , Piel/efectos de la radiación , Quemadura Solar/complicaciones , Rayos Ultravioleta , Vitis , Animales , Apoptosis , Compuestos de Bifenilo/metabolismo , Citocinas/análisis , Modelos Animales de Enfermedad , Femenino , Depuradores de Radicales Libres/análisis , Humanos , Ratones , Ratones Pelados , Picratos/metabolismo , Dímeros de Pirimidina/análisis , Distribución Aleatoria , Semillas , Piel/efectos de los fármacos , Piel/patología , Quemadura Solar/metabolismoRESUMEN
OBJECTIVE: The present study evaluated the effects on gestation, in terms of oxidative stress, of two antioxidant factors-vitamin E and coenzyme Q10-during pregnancy, with the purpose of applying the results in further human clinical practice. METHODS: For each aspect we have studied, we used three types of female rats of Wistar race (un-pregnant, primiparous, multiparous), divided in 10 rats/group. From the blood we have sampled, we have determined the oxidative stress (OS) markers: malondialdehyde (MDA) and carbonylated proteins (CP), but also the markers of the antioxidant defense: the hydrogen donor capacity of the plasma (HD) and the sulfhydryl groups (SH). RESULTS: Vitamin E administration determines significant decreases of MDA and significant increases of CP and HD at primiparous, and also significant increases of SH groups at multiparous. In the case of pregnant animals that received CoQ10 in antioxidant complexes, we have observed an increase of oxidative stress (OS)-MDA in primiparous and CP in multiparous. CONCLUSIONS: In the case of Vitamin E, taking into account the benefits on redox homeostasis, the decrease of OS, the authors recommend vitamin E administration during pregnancy. However, because of the increase of the OS in the case of pregnant animals, the authors do not recommend the administration of CoQ(10) in antioxidant complexes during pregnancy.
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Antioxidantes/farmacología , Estrés Oxidativo/efectos de los fármacos , Ubiquinona/análogos & derivados , Vitamina E/farmacología , Animales , Femenino , Humanos , Hidrógeno/sangre , Malondialdehído/metabolismo , Embarazo , Carbonilación Proteica/efectos de los fármacos , Ratas , Ratas Wistar , Compuestos de Sulfhidrilo/metabolismo , Ubiquinona/administración & dosificación , Ubiquinona/farmacología , Vitamina E/administración & dosificaciónRESUMEN
Single-walled carbon nanotubes (SWCNTs) have been proposed for various medical applications. However, their safety for human administration has not been yet fully demonstrated. In vitro studies have pointed oxidative stress as a mechanism involved in their cytotoxic effects. In the present study we have evaluated the capacity of DNA functionalized SWCNTs to induce oxidative stress in blood after intraperitoneal (ip) administration in rats. The presence of SWCNTs in blood was confirmed by Raman spectroscopy 30 minutes after their ip administration. Oxidative stress parameters (malondialdehyde - MDA, protein carbonyls - PC, antioxidant capacity measured as hydrogen donating capacity - HD, sulfhydryl groups - SH, glutathione - GSH and nitrites - NO) were assessed in blood at 3, 6, 24, respectively, and 48 hours after ip injection. MDA, PC and NO exhibited a significant increase at 3-6 hours interval from exposure, followed by a recovery trend. The levels of HD reached a bottom level at 6 hours after administration, while SH strongly decreased at 3 hours interval and increased slightly up to 48 hours without attending the initial values. GSH level recorded an increasing tendency at the 3rd hour, an incomplete recovery process at 24 hours followed by a secondary significant increase following a 48-hour interval. Significant inverse correlations were obtained between the PC and SH levels and between the NO and HD values. In conclusion, the ip administration of DNA functionalized SWCNT in rats results in oxidative stress generation in plasma, with a transient pattern of evolution.
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Nanotubos de Carbono/efectos adversos , Estrés Oxidativo/fisiología , Especies Reactivas de Oxígeno/sangre , Animales , Glutatión/sangre , Inyecciones Intraperitoneales , Malondialdehído/sangre , Modelos Animales , Óxido Nítrico/sangre , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
The oxidative effects of photodynamic therapy with 5,10,15,20-tetrakis(4-methoxyphenyl) porphyrin (TMP) and Zn-5,10,15,20-tetrakis(4-methoxyphenyl) porphyrin (ZnTMP) were evaluated in Wistar rats subcutaneously inoculated with Walker 256 carcinoma. The animals were irradiated with red light (λ = 685 nm; D = 50 J/cm2; 15 min) 3 h after intra-peritoneal administration of 10 mg/kg body weight of porphyrins. The presence of free radicals in tumours after photodynamic therapy with TMP and ZnTMP revealed by chemiluminescence of luminol attained the highest level at 18 h after irradiation. Lipid peroxides measured as thiobarbituric-reactive substances and protein carbonyls, which are indices of oxidative effects produced on susceptible biomolecules, were significantly increased in tumour tissues of animals 24 h after photodynamic therapy. The levels of thiol groups and total antioxidant capacity in the tumours were decreased. The activities of antioxidant enzymes superoxide dismutase and glutathione peroxidase were also increased in tumour tissues after photodynamic therapy. Increased levels of plasma lipid peroxides as well as changes in the levels of erythrocyte antioxidant enzyme activities suggest possible systemic effects of photodynamic therapy with TMP and ZnTMP.
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Carcinoma 256 de Walker/tratamiento farmacológico , Oxidorreductasas/análisis , Fotoquimioterapia , Fármacos Fotosensibilizantes/uso terapéutico , Porfirinas/uso terapéutico , Animales , Antioxidantes/análisis , Antioxidantes/metabolismo , Carcinoma 256 de Walker/metabolismo , Radicales Libres/análisis , Radicales Libres/sangre , Radicales Libres/metabolismo , Peróxidos Lipídicos/análisis , Peróxidos Lipídicos/sangre , Peróxidos Lipídicos/metabolismo , Luminiscencia , Luminol/química , Masculino , Oxidación-Reducción/efectos de la radiación , Oxidorreductasas/sangre , Oxidorreductasas/metabolismo , Consumo de Oxígeno/efectos de los fármacos , Fármacos Fotosensibilizantes/metabolismo , Fármacos Fotosensibilizantes/farmacología , Porfirinas/metabolismo , Porfirinas/farmacología , Carbonilación Proteica/efectos de la radiación , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Compuestos de Sulfhidrilo/análisis , Compuestos de Sulfhidrilo/sangre , Compuestos de Sulfhidrilo/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/análisis , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Factores de TiempoRESUMEN
Photodynamic therapy (PDT) mediated by oxidative stress causes direct tumor cell damage as well as microvascular injury. To improve this treatment new photosensitizers are being synthesized and tested. We evaluated the effects of PDT with 5,10,15,20-tetrakis(4-methoxyphenyl)-porphyrin (TMPP) and its zinc complex (ZnTMPP) on tumor levels of malondialdehyde (MDA), reduced glutathione (GSH) and cytokines, and on the activity of caspase-3 and metalloproteases (MMP-2 and -9) and attempted to correlate them with the histological alterations of tumors in 3-month-old male Wistar rats, 180 ± 20 g, bearing Walker 256 carcinosarcoma. Rats were randomly divided into five groups: group 1, ZnTMPP+irradiation (IR) 10 mg/kg body weight; group 2, TMPP+IR 10 mg/kg body weight; group 3, 5-aminolevulinic acid (5-ALA+IR) 250 mg/kg body weight; group 4, control, no treatment; group 5, only IR. The tumors were irradiated for 15 min with red light (100 J/cm², 10 kHz, 685 nm) 24 h after drug administration. Tumor tissue levels of MDA (1.1 ± 0.7 in ZnTMPP vs 0.1 ± 0.04 nmol/mg protein in control) and TNF-α (43.5 ± 31.2 in ZnTMPP vs 17.3 ± 1.2 pg/mg protein in control) were significantly higher in treated tumors than in controls. Higher caspase-3 activity (1.9 ± 0.9 in TMPP vs 1.1 ± 0.6 OD/mg protein in control) as well as the activation of MMP-2 (P < 0.05) were also observed in tumors. These parameters were correlated (Spearman correlation, P < 0.05) with the histological alterations. These results suggest that PDT activates the innate immune system and that the effects of PDT with TMPP and ZnTMPP are mediated by reactive oxygen species, which induce cell membrane damage and apoptosis.
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Animales , Masculino , Ratas , Ácido Aminolevulínico/uso terapéutico , /tratamiento farmacológico , Metaloporfirinas/uso terapéutico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/uso terapéutico , Porfirinas/uso terapéutico , Apoptosis , /metabolismo , Glutatión/análisis , Peroxidación de Lípido , Malondialdehído/análisis , Metaloproteinasa 9 de la Matriz/análisis , /análisis , Estrés Oxidativo , Distribución Aleatoria , Ratas Wistar , Factor de Necrosis Tumoral alfa/análisisRESUMEN
Photodynamic therapy (PDT) mediated by oxidative stress causes direct tumor cell damage as well as microvascular injury. To improve this treatment new photosensitizers are being synthesized and tested. We evaluated the effects of PDT with 5,10,15,20-tetrakis(4-methoxyphenyl)-porphyrin (TMPP) and its zinc complex (ZnTMPP) on tumor levels of malondialdehyde (MDA), reduced glutathione (GSH) and cytokines, and on the activity of caspase-3 and metalloproteases (MMP-2 and -9) and attempted to correlate them with the histological alterations of tumors in 3-month-old male Wistar rats, 180 ± 20 g, bearing Walker 256 carcinosarcoma. Rats were randomly divided into five groups: group 1, ZnTMPP+irradiation (IR) 10 mg/kg body weight; group 2, TMPP+IR 10 mg/kg body weight; group 3, 5-aminolevulinic acid (5-ALA+IR) 250 mg/kg body weight; group 4, control, no treatment; group 5, only IR. The tumors were irradiated for 15 min with red light (100 J/cm², 10 kHz, 685 nm) 24 h after drug administration. Tumor tissue levels of MDA (1.1 ± 0.7 in ZnTMPP vs 0.1 ± 0.04 nmol/mg protein in control) and TNF-α (43.5 ± 31.2 in ZnTMPP vs 17.3 ± 1.2 pg/mg protein in control) were significantly higher in treated tumors than in controls. Higher caspase-3 activity (1.9 ± 0.9 in TMPP vs 1.1 ± 0.6 OD/mg protein in control) as well as the activation of MMP-2 (P < 0.05) were also observed in tumors. These parameters were correlated (Spearman correlation, P < 0.05) with the histological alterations. These results suggest that PDT activates the innate immune system and that the effects of PDT with TMPP and ZnTMPP are mediated by reactive oxygen species, which induce cell membrane damage and apoptosis.
Asunto(s)
Ácido Aminolevulínico/uso terapéutico , Carcinoma 256 de Walker/tratamiento farmacológico , Metaloporfirinas/uso terapéutico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/uso terapéutico , Porfirinas/uso terapéutico , Animales , Apoptosis , Carcinoma 256 de Walker/metabolismo , Glutatión/análisis , Peroxidación de Lípido , Masculino , Malondialdehído/análisis , Metaloproteinasa 2 de la Matriz/análisis , Metaloproteinasa 9 de la Matriz/análisis , Estrés Oxidativo , Distribución Aleatoria , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/análisisRESUMEN
The rapid expansion of laparoscopic surgery has led to the development of training methods for acquiring technical skills. The importance and complexity of laparoscopic liver surgery are arguments for developing a new integrated system of teaching, learning and evaluation, based on modern educational principles, on flexibility allowing wide accessibility among surgeons. This paper presents the development of e-learning platform designed for training in laparoscopic liver surgery and pre-planning of the operation in a virtual environment. E-learning platform makes it possible to simulate laparoscopic liver surgery remotely via internet connection. The addressability of this e-learning platform is large, being represented by young surgeons who are mainly preoccupied by laparoscopic liver surgery, as well as experienced surgeons interested in obtaining a competence in the hepatic minimally invasive surgery.
Asunto(s)
Instrucción por Computador , Internet , Laparoscopía , Hígado/cirugía , Interfaz Usuario-Computador , Competencia Clínica/normas , Educación Médica Continua/organización & administración , Educación de Postgrado en Medicina/organización & administración , Humanos , Laparoscopía/métodos , Aprendizaje , Rumanía , Análisis y Desempeño de TareasRESUMEN
Coumarin-induced skin necrosis represents a clinical entity that occurs very rarely, with an approximate incidence of 0.01-0.1% at patients following oral anticoagulant therapy. Most of the cases become clinical manifest between the 3rd and 6th of anticoagulant treatment (there were reports of late onset of skin necrosis after 15 years of anticoagulant therapy) and the most involved areas include breast, buttocks and thighs microcirculation-rich areas. Early symptoms include paresthesia and sensation of tension associated with an erythematous flush in the affected area. Lesions are well demarcated, painful, initially erythematous or hemorrhagic, with the onset of skin necrosis in the end stage. Early lesions can be reversible with the discontinuation of anticoagulant therapy, but skin necrosis can reoccur even without any other coumarin based treatment. We report the case of a 55-year-old female who presented with coumarin-induced skin necrosis affecting the right breast and the right deltoid area.