The effects of cocoa supplementation, caloric restriction, and regular exercise, on oxidative stress markers of brain and memory in the rat model

The effects of treadmill running (8 weeks, 5 times/week, 1h/day at 27 m/min), caloric restriction, and cocoa supplementation on brain function and oxidative stress markers were tested. The Morris maze test was used to appraise rat memory. Regular exercise significantly improved spatial learning performance. The level of oxidative stress was measured by the concentration of carbonylated proteins. The free radical concentration increased in brain of the training groups but not the controls. The content of reactive carbonyl derivates did not change with exercise, suggesting that the increased production of reactive oxygen species (ROS) were well tolerated in this experimental model. Caloric restriction (CR) decreased the accumulation of free radicals in the frontal lobe. The protein content of brain-derived neutrophic factors (BDNFs) was evaluated and changes did not occur either with exercise or cocoa supplementation treatments. These data did not show significant effects of the administration of cocoa (2% w/w) on the concentration of ROS, BDNF or on spatial memory. Conversely, exercise and CR can play a role in ROS generation and brain function

Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores

Background: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers. Methods: 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)-negative (PRSER-), or ER-positive (PRSER+) breast cancer risk. Results: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions. Conclusions: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.Peer reviewe

Aminoguanidin-kezeles pozitiv hatasa a peroxinitrit-termelodesre es szivhipertrofiara streptozotocinnal indukalt diabeteses patkanyokban

The effect and possible mechanisms of action of aminoguanidine (a preferential iNOS inhibitor) has been studied on cardiovascular damages and overproduction of reactive nitrogen species in streptozotocin-induced diabetic rats. MATERIALS AND METHODS: 40 rats were divided into five groups (control and diabetic, with or without aminoguanidine treatment, diabetic with insulin treatment) and oxidative stress parameters were examined. Tissue nitric oxide levels were determined by EPR spectroscopy, while peroxynitrite generation by a chemiluminescence method. Cardiac hypertrophy, blood metabolic parameters (blood glucose, HbA1c, fructosamine), as well as tissue protein carbonyl levels were also determined. RESULTS: Diabetic animals showed increased nitric oxide and peroxynitrite generation in the aorta along with a significant hypertrophy and protein carbonylation of the cardiac tissue. Both aminoguanidine and insulin treatment suppressed high levels of nitric oxide and peroxynitrite in the vasculature, but only aminoguanidine was able to prevent hypertrophic alterations and to reduce protein carbonylation in the heart. CONCLUSIONS: The results show that (1) aminoguanidine reduces nitric oxide production and prevents cardiac hypertrophy, (2) insulin therapy improves carbohydrate metabolism, reduces nitrosative stress but has no effect on cardiac hypertrophy. Cardiac hypertrophy in diabetes is strongly correlated with non-enzymatic glycation. Aminoguanidine prevented hypertrophy by blocking the formation of advanced glycation end products rather than via other mechanisms

Beneficial effects of aminoguanidine on the cardiovascular system of diabetic rats

BACKGROUND: The study focused on investigating the effect of aminoguanidine on cardiovascular damages in diabetes and the possible mechanisms of its action. METHODS: Aminoguanidine (AMNG) was used to treat streptozotocin-induced diabetic rats, and the effects were compared to those obtained under insulin treatment. Blood metabolic parameters, *NO and ONOO- as well as protein carbonyl levels and cardiac hypertrophy were determined. RESULTS: Diabetic animals showed increased *NO levels and markedly increased ONOO- generation in the aorta, along with a significant hypertrophy and protein carbonylation in the cardiac tissue. Both AMNG and insulin treatment suppressed the levels of overproduced *NO or ONOO- in the vasculature, but only AMNG was able to prevent hypertrophic alterations and reduce protein carbonylation in the cardiac tissue. CONCLUSIONS: Oxidative protein modification, together with cardiac hypertrophy and high generation of *NO and ONOO-, are important early events in the development of cardiovascular complications in diabetes. Aminoguanidine could prevent hypertrophy through inhibition of production of nonenzymatic glycation products rather than via inhibition of *NO production

Szabadgyokok es reaktiv nitrogen speciesek szerepe a diabetes kesoi szovodmenyeinek kialakulasaban patkanyban

In this time-course study the levels of different reactive species, especially those of nitric oxide and peroxynitrite were determined in streptozotocin-induced diabetic rat tissues at different time-points after the onset of the disease, before the development of histopathological damages. Significantly higher steady state free radical concentrations were found in the liver 3 weeks after the onset of diabetes, compared to age matched control groups. Increased nitric oxide levels in diabetic vasculature and kidney, and its rapid reaction with reactive oxygen species, resulted in high peroxynitrite generation. This suggested the onset of processes characteristic to premature aging of the endothelium. According to the histopathological results, there were no signs of late complications in the tissues up to seven weeks after induction of diabetes. In conclusion, the authors' experimental evidences support the idea of a complex role for nitric oxide, reactive oxygen species and peroxynitrite in the development of early diabetic tissue injury before the evolution of late complications. This study showed for the first time a time-course dependence for changes in nitric oxide production in diabetic tissues compared to age-matched controls at an early stage of the disease. These results suggest that oxidative stress in increased at a very early stage of diabetes and, in particular, that high levels of nitric oxide and peroxynitrite could play a decisive role in the development of late complications in the diabetic vasculature and kidney

A Koragyermekkori Evés-alvászavar Ambulancia klinikai protokollja

A Heim Pál Országos Gyermekgyógyászati Intézet Madarász utcai Koragyermekkori Evés-alvászavar Ambulanciájának klinikai protokollját, az ellátás hatékonyságának nyomon követésére kialakított kutatási program módszertanát, és végül e kutatás elsô eredményeit háromrészes közleményünkben mutatjuk be. A fekvôbetegháttérrel is rendelkezô ambulancia az egészségügyi szolgáltatásban – interdiszciplináris modell keretében – elsôként nyújtott szervezett ellátást hazánkban a kora gyermekkori állapot-, érzelem- és viselkedésszabályozási problémákat mutató csecsemôk, kisgyermekek és családjaik számára. Sorozatunk elsô részében az ambulancia – nemzetközi szakirodalom, valamint saját korábbi tapasztalataink alapján kialakított – klinikai protokollját ismertetjük. Szakirodalmi bevezetônkben a kora gyermekkori lelki egészség zavarai közül kifejezetten az alvás- és az evészavarok ellátási körét érintjük. A nemzetközi szakirodalom rövid összefoglalásával támasztjuk alá a 2017-ben indult ambulancia ellátótevékenységének felépítését. Írásunknak a célja az, hogy az ambulancia klinikai munkájának részletes ismertetése más egészségügyi intézmények számára is ösztönzést jelentsen hasonló interdiszciplináris ellátások megszervezésére

A Koragyermekkori Evés-alvászavar Ambulancia ellátási modelljét kísérô tudományos nyomon követés módszertana = Methodology of scientific monitoring of care in the outpatient clinic of early childhood eating and sleep disorders

Háromrészes cikksorozatunkban a Heim Pál Országos Gyermekgyógyászati Intézet Madarász utcai Koragyermekkori EvésAlvászavar Ambulanciájának klinikai protokollját, az ellátás tudományos nyomonkö vetésének modelljét és kutatásunk elsô statisztikai eredményeit mutatjuk be. Az osztályos háttérrel is rendelkezô ambulancia az egészségügyi szektoron belül – interdiszciplináris ellátási modell keretében – elsôként nyújtott szervezett ellátást hazánkban a kora gyermekkori állapot-, érzelemés viselkedésszabályozási problémákat mutató csecsemôk, kisgyermekek és családjaik számára. = In a three-part article series, we present the clinical protocol used by the Early Childhood Eating and Sleep Disorders Outpatient Clinic at Madarász Street of the Heim Pál National Pediatric Institute; a model of the scientific monitoring of the care; and the first results obtained by this monitoring research. The Clinic that also has a hospital background was the first in the Hungarian health care system to pro - vide organized care for families of infants and young children struggling with early childhood emotional and behavioral regulation problems within a framework of interdisciplinary care model

Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores

Background: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers. Methods: 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)-negative (PRSER-), or ER-positive (PRSER+) breast cancer risk. Results: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions. Conclusions: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.Peer reviewe