Search Results (7)

Traumatic brain injuries represent a leading cause of death and disability in the paediatric and adult populations. Moderate-to-severe injuries are associated with blood–brain barrier dysfunction, the development of cerebral oedema, and neuroinflammation. Antagonists of the tachykinin NK1 receptor have been proposed as potential agents for the post-injury treatment of TBI. We report on the identification of EUC-001 as a potential clinical candidate for development as a novel TBI therapy. EUC-001 is a selective NK1 antagonist with a high affinity for the human NK1 receptor (Ki 5.75 × 10⁻¹⁰ M). It has sufficient aqueous solubility to enable intravenous administration, whilst still retaining good CNS penetration as evidenced by its ability to inhibit the gerbil foot-tapping response. Using an animal model of TBI, the post-injury administration of EUC-001 was shown to restore BBB function in a dose-dependent manner. EUC-001 was also able to ameliorate cerebral oedema. These effects were associated with a significant reduction in post-TBI mortality. In addition, EUC-001 was able to significantly reduce functional deficits, both motor and cognitive, that normally follow a severe injury. EUC-001 is proposed as an ideal candidate for clinical development for TBI. Full article

Dapagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor used for the treatment of diabetes. This study examines the effects of dapagliflozin on human islets, focusing on alpha and beta cell composition in relation to function in vivo, following treatment of xeno-transplanted diabetic mice. Mouse beta cells were ablated by alloxan, and dapagliflozin was provided in the drinking water while controls received tap water. Body weight, food and water intake, plasma glucose, and human C-peptide levels were monitored, and intravenous arginine/glucose tolerance tests (IVarg GTT) were performed to evaluate islet function. The grafted human islets were isolated at termination and stained for insulin, glucagon, Ki67, caspase 3, and PDX-1 immunoreactivity in dual and triple combinations. In addition, human islets were treated in vitro with dapagliflozin at different glucose concentrations, followed by insulin and glucagon secretion measurements. SGLT2 inhibition increased the animal survival rate and reduced plasma glucose, accompanied by sustained human C-peptide levels and improved islet response to glucose/arginine. SGLT2 inhibition increased both alpha and beta cell proliferation (Ki67⁺glucagon⁺ and Ki67⁺insulin⁺) while apoptosis was reduced (caspase3⁺glucagon⁺ and caspase3⁺insulin⁺). Alpha cells were fewer following inhibition of SGLT2 with increased glucagon/PDX-1 double-positive cells, a marker of alpha to beta cell transdifferentiation. In vitro treatment of human islets with dapagliflozin had no apparent impact on islet function. In summary, SGLT2 inhibition supported human islet function in vivo in the hyperglycemic milieu and potentially promoted alpha to beta cell transdifferentiation, most likely through an indirect mechanism. Full article

Non-thermal plasma activated water (PAW) has recently emerged as a powerful antimicrobial agent. Despite numerous potential bio-medical applications, studies concerning toxicity in live animals, especially after long-term exposure, are scarce. Our study aimed to assess the effects of long-term watering with PAW on the health of CD1 mice. PAW was prepared from distilled water with a GlidArc reactor according to a previously published protocol. The pH was 2.78. The mice received PAW (experimental group) or tap water (control group) daily for 90 days as the sole water source. After 90 days, the following investigations were performed on the euthanatized animals: gross necropsy, teeth mineral composition, histopathology, immunohistochemistry, hematology, blood biochemistry, methemoglobin level and cytokine profile. Mice tolerated PAW very well and no adverse effects were observed during the entire period of the experiment. Histopathological examination of the organs and tissues did not reveal any structural changes. Moreover, the expression of proliferation markers PCNA and Ki67 has not been identified in the epithelium of the upper digestive tract, indicating the absence of any pre- or neoplastic transformations. The results of our study demonstrated that long-term exposure to PAW caused no toxic effects and could be used as oral antiseptic solution in dental medicine. Full article

Maternal high fat diet (HFD) and obesity during pregnancy increase female offspring${}^{\prime }$s mammary cancer risk in animal studies. We aimed to observe whether the consumption of grape juice during pregnancy can reverse this risk. During pregnancy and lactation, female Wistar rats were fed either a control or HFD and also received grape juice or tap water. At the age of 50 days, female offspring were euthanized, and mammary glands were collected to assess changes in biomarkers of increased mammary cancer risk. Maternal HFD increased the number of terminal end buds in offspring’s mammary glands and promoted cell proliferation (ki67). Maternal grape consumption blocked these effects. Apoptosis marker caspase 7, but not caspase 3, was reduced in the HFD offspring. HFD offspring also exhibited a reduction in the indicators of cell cycle regulation (p27, p21) and an ability to maintain DNA integrity (reduced p53). Maternal grape juice did not have any effect on these endpoints in the HFD offspring but reduced caspase 7 and p53 levels in the control offspring, perhaps reflecting reduced cellular stress. Maternal HFD increased oxidative stress marker GPx1 mRNA expression, and grape juice increased the levels of GPx2 in both the control and HFD offspring. HFD increased XBP1/Xbp1s, Atf4 and Atf6 mRNA expression and reduced ATF6 and CHOP protein levels. Maternal grape juice reversed the increase in XBP1/Xbp1s, Atf4 and Atf6 in the HFD offspring. PPAR was downregulated in the HFD group, and grape juice reversed this effect. Grape juice also reduced the levels of HER2 and IRS, both in the control and HFD offspring. In conclusion, maternal grape juice supplementation reversed some of the biomarkers that are indicative of increased breast cancer risk in the HFD offspring. Full article

A growing number of studies support the theory that physical activity can effectively foster the cognitive function of children with attention-deficit hyperactivity disorder (ADHD). The present study examines the effect of acute moderate physical activity on the executive functions and attention performance of (1) typically developing children (without psychological, psychiatric or neurological diagnosis and/or associated treatment stated in their medical history); (2) treatment-naïve ADHD children; and (3) medicated children with ADHD. In the current study, a total sample of 150 (50 non-medicated, 50 medicated, and 50 typically developing) children between the ages of 6 and 12 took part in the experiment. The Mini International Neuropsychiatric Interview for Children and Adolescents (MINI Kid) was used to measure ADHD and the child version of the Test of Attentional Performance (KiTAP) was applied to evaluate the children’s attentional and executive function performance before and after two types of intervention. In order to compare the effects of physical activity and control intervention, half of the children from each group (25 participants) took part in a 20-min long, moderately intense physical activity session on the 60–80% of their maximum heart rate, while watching a cartoon video. In the control condition, the other half of the children (25 participants) from each group watched the same cartoon video for 20 min while seated. Physical activity (compared to the just video watching control condition) had a significantly positive influence on 2 out of 15 measured parameters (median reaction time in the alertness task and error rates in the divided attention task) for the medicated group and on 2 out of the 15 measured variables (number of total errors and errors when distractor was presented, both in the distractibility task) regarding the treatment-naïve group. Future studies should focus on finding the optimal type, intensity, and duration of physical activity that could be a potential complementary intervention in treating deficits regarding ADHD in children. Full article

The emerging literature reports that children with Attention-Deficit/Hyperactivity Disorder (ADHD) show deficits in executive functioning. To date, the combination of drug therapy with certain evidence-based non-medication interventions has been proven to be the most effective treatment for ADHD. There is a gap in the literature regarding comparing the executive functions (EF) of treatment naïve and medicated children with ADHD with both each other and typically developing children. Altogether, 50 treatment naïve and 50 medicated children with ADHD and 50 typically developing children between the ages of six and 12 were enrolled. The Mini International Neuropsychiatric Interview for Children and Adolescents (Mini Kid) and the Test of Attentional Performance for Children (KiTAP) measures were employed. Treatment naïve children with ADHD showed weaker performance on most executive function measures (12 out of 15) than either the medicated ADHD group or the controls. There were no significant differences between the medicated ADHD children and typically developing children in most KiTAP parameters (10 out of 15). Executive function impairments were observable in treatment naïve ADHD children, which draws attention to the importance of treating ADHD. Future studies should focus on the specific effects of stimulant medication on executive functions. Full article

This research revealed the children with difficulties in attentional functions among healthy children attending primary school and aimed to identify the possible sociodemographic factors, such as the child’s age, gender, and school grade, that could influence attentive performance. The participants were 105 children aged 6–10 years (M age = 8.6; SD = 1.04), attending primary schools. Family economic condition was mostly at a medium level (63.5%), and parents most frequently had 13 years of schooling. The computerized test KiTAP was administered to children to assess their attentional functions. Results showed a higher frequency of omissions and false alarms and a reduced speed in alertness, go/no-go, and sustained attention tasks compared to Italian norms. Hierarchical regression analyses were run with school grade, gender, and current age as independent variables and mean reaction times (and standard deviation), number of omissions, and false alarms as dependent ones. The results showed that male gender and attending a lower grade impacted on lower attentional performance in several subtests. Girls showed the best performances in tests of distractibility and impulsive reaction tendencies, while higher school grade positively influenced divided and sustained attention. These results could be useful to identify children with major attentional difficulties, and some recommendations for future studies and the implementation of attention empowerment programmes are proposed. Full article