RESUMEN
Schizophrenia (SZ) is a mental disorder with a strong genetic basis as well as epigenetic aspects. Siblings of patients with SZ can share certain endophenotypes with the patients, suggesting that siblings may be important for distinguishing between trait and state markers. In the current study, we aimed to characterize the balance between pro-BDNF/mature BDNF and its receptors p75NTR/TrkB, which are tPA-BDNF pathways proteins and are thought to play a role in synaptic pruning, as a possible endophenotype of schizophrenia. Forty drug-naïve patients with first-episode psychosis (FEP) matched for age, gender, and level of education, 40 unaffected siblings (UAS) of patients with FEP, and 67 healthy controls (HC) were included in the study. Blood samples were collected from all participants to determine BDNF, pro-BDNF, TrkB and p75NTR, PAI1, tPA, ACTH, and cortisol levels. We showed that levels of proteins of the tPA-BDNF pathway as well as the pro-BDNF/m-BDNF and p75NTR/TrkB ratios could successfully differentiate FEP and their siblings from the HCs by using ROC analysis. Plasma levels of m-BDNF were found to be the lowest in the healthy siblings and highest in the HCs with statistically significant differences between all 3 groups. The plasma level of pro-BDNF in the HC group was similar to the FEP patients, the same in the healthy siblings of the FEP patients. Our data support the hypothesis that imbalance between neurotrophic and apoptotic proteins might occur in SZ and this imbalance could be an endophenotype of the disease.
Asunto(s)
Trastornos Psicóticos , Esquizofrenia , Humanos , Factor Neurotrófico Derivado del Encéfalo/genética , BiomarcadoresRESUMEN
OBJECTIVE: Many hypotheses have put forward to better understand the pathogenesis of schizophrenia (SZ), such as synaptic pruning, stress-diathesis, neurodevelopment, neurodegeneration and neurotransmitter hypothesis; nonetheless, this pathogenesis still remains a mystery. The current study was designed with the hypothesis that impairment of a balance between pro-BDNF/mature BDNF and their receptors p75NTRK/TrkB may cause synaptic pruning in the pathogenesis of psychotic disorders. METHODS: Sixty-five drug-naïve patients with first-episode psychosis (FEP) who applied to outpatient clinics and were diagnosed according to DSM-5 as well as 65 healthy controls (HC) were included in the study. Symptoms at the time of evaluation were assessed with the PANSS scale by an experienced psychiatrist. Blood samples were collected from all participants to determine BDNF, pro-BDNF, TrkB and p75NTR, PAI1, tPA, ACTH and cortisol levels. RESULTS: Mature BDNF, TrkB and PAI-1, tPA levels were significantly lower while the levels of ACTH and cortisol were significantly higher in FEP patients compared to HC. No significant difference was found in pro-BDNF and p75NTR levels between the two independent groups. The pro-BDNF/mature BDNF and the p75NTR/TrkB ratios were significantly higher in FEP patients compared to HC. Moreover, the pro-BDNF/mature BDNF and the p75NTR/TrkB ratios were found to be significantly associated with the pathogenesis of SZ in a hierarchical regression model. DISCUSSION: Imbalance between neurotrophic and apoptotic proteins such as pro-BDNF/mature BDNF and p75NTR/TrkB may be take part pathogenesis of synaptic pruning in psychotic disorders.
Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Trastornos Psicóticos , Estudios de Casos y Controles , Humanos , Glicoproteínas de Membrana , Proteínas del Tejido Nervioso , Inhibidor 1 de Activador Plasminogénico , Receptor trkB , Receptores de Factor de Crecimiento Nervioso , Activador de Tejido PlasminógenoRESUMEN
This study aims to determine the potential protective effects of ferulic acid against cisplatin-induced nephrotoxicity and to compare its effect with curcumin, a well-known protective agent against cisplatin- induced toxicity in rats. Administration of cisplatin resulted in high BUN (Blood Urea Nitrogen), creatinine, MDA (Malondialdehyde), MPO (Myeloperoxidase), TOS (Total Oxidative Status), PtNT (Protein Nitrotyrosine) levels (p<0.05). Histological observations showed abnormal morphology of kidney; in addition with appearance of TUNEL positive cells indicating apoptosis in cisplatin administered group. HO-1 (Heme Oxygenase-1) levels measured by RT-PCR (Real Time Polymerase Chain Reaction), and TAS (Total Antioxidative Status) revealed antioxidant depletion due to cisplatin toxicity in animals (p<0.05). All parameters showed improvement in groups treated with ferulic acid (p<0.05). Ferulic acid treatment was found significant in preventing oxidative stress, increasing antioxidative status and regaining histological parameters to normal, indicating nephroprotective and antioxidant effects of this phenolic compound.
Asunto(s)
Ácidos Cumáricos/uso terapéutico , Enfermedades Renales/tratamiento farmacológico , Sustancias Protectoras/uso terapéutico , Animales , Nitrógeno de la Urea Sanguínea , Cisplatino , Ácidos Cumáricos/farmacología , Curcumina/farmacología , Curcumina/uso terapéutico , Hemo Oxigenasa (Desciclizante)/genética , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Enfermedades Renales/inducido químicamente , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Masculino , Malondialdehído/metabolismo , Peroxidasa/metabolismo , Sustancias Protectoras/farmacología , ARN Mensajero/metabolismo , Ratas Wistar , Tirosina/análogos & derivados , Tirosina/metabolismoRESUMEN
The objective of this study was to establish reference intervals for growth arrest-specific 6 (GAS6), a vitamin K-dependent protein, in human adult plasma according to the Guideline of Clinical and Laboratory Standards Institute (CLSI) C28-A3. Blood samples were collected from 308 healthy volunteers aged 18-72 (157 female, 151 male). A non-parametric approach was used to calculate the reference interval. The plasma GAS6 reference interval was determined, with 90% confidence interval: the lower limit (2.5 percentile) was 2.5 (1.9-3.1) µg/L and the upper limit (97.5 percentile) = 18.8 (18.0-22.3) µg/L. Harris-Boyd's test did not suggest partitioning by age or gender: medians for males [7.8 (5.8-10.7) µg/L] and females [9.9 (7.1-13.5) µg/L]. Three age-subgroups were tested: 18-29 years (n = 168); 30-44 years (n = 73); 45-72 years (n = 67). The intra- and inter-assay variations were 12.6% (mean, 5.2 ± 0.7 µg/L) and 14.0% (mean, 9.2 ± 1.3 µg/L), respectively. The mean recovery was 104%. This study reports plasma GAS6 reference intervals established first according to the guideline of CLSI C28-A3.
Asunto(s)
Péptidos y Proteínas de Señalización Intercelular/sangre , Adolescente , Adulto , Anciano , Análisis de Varianza , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Guías de Práctica Clínica como Asunto , Valores de Referencia , Reproducibilidad de los ResultadosRESUMEN
AIM: To investigate the effects of long term pretreatment with low-, medium- and high-dose aspirin (acetylsalicylic acid, ASA) on a model of acute pancreatitis (AP) induced in rats. METHODS: Forty male Wistar rats were used. Three experimental groups, each consisting of eight animals, received low- (5 mg/kg per day), medium- (150 mg/kg per day) and high-dose (350 mg/kg per day) ASA in supplemented pellet chow for 100 d. Eight animals, serving as the AP-control group, and another eight, serving as reference value (RV) group, were fed with standard pellet chow for the same period. After pretreatment, AP was induced in the experimental animals by intraperitoneal administration of cerulein (2 × 50 µg/kg), while the RV group received saline in the same way. Twelve hours after the second injection, the animals were sacrificed. Pancreatic tissue and plasma samples were collected. One part of the collected pancreatic tissues was used for histopathological evaluation, and the remaining portion was homogenized. Cytokine levels [tumor necrosis factor, interleukin (IL)-1ß, IL-6], hemogram parameters, biochemical parameters (amylase and lipase), nuclear factor-κB, aspirin triggered lipoxins and parameters related to the antioxidant system (malondialdehyde, nitric oxide, hemeoxygenase-1, catalase and superoxide dismutase) were measured. RESULTS: Cerulein administration induced mild pancreatitis, characterized by interstitial edema (total histopathological score of 5.88 ± 0.44 vs 0.25 ± 0.16, P < 0.001). Subsequent pancreatic tissue damage resulted in an increase in amylase (2829.71 ± 772.48 vs 984.57 ± 49.22 U/L, P = 0.001) and lipase (110.14 ± 75.84 U/L vs 4.71 ± 0.78 U/L, P < 0.001) in plasma, and leucocytes (6.89 ± 0.48 vs 4.36 ± 0.23, P = 0.001) in peripheral blood. Cytokines, IL-1ß (18.81 ± 2.55 pg/µg vs 6.65 ± 0.24 pg/µg, P = 0.002) and IL-6 (14.62 ± 1.98 pg/µg vs 9.09 ± 1.36 pg/µg, P = 0.04) in pancreatic tissue also increased. Aspirin pretreatment reduced the increase in the aforementioned parameters to a certain degree and partially improved the histopathological alterations caused by cerulein. No evidence of side effects related to chronic ASA administration (e.g., inflammation or bleeding) was observed in the gastrointestinal tract in macroscopic and histopathological examination. CONCLUSION: Long term ASA pretreatment could prevent and/or ameliorate certain hematological, serological and histological alterations caused by cerulein-induced AP.