Pelargonidin Improves Passive Avoidance Task Performance in a Rat Amyloid Beta25-35 Model of Alzheimer’s Disease Via Estrogen Receptor Independent Pathways

Alzheimer’s disease (AD) is a disorder with multiple pathophysiological causes, destructive outcomes, and no available definitive cure. Pelargonidin (Pel), an anthocyanin derivative, is an estrogen receptor agonist with little estrogen side effects. This study was designed to assess Pel memory enhancing effects on the a rat Amyloid Beta25-35 (Aβ) intrahippocampal microinjections model of AD in the passive avoidance task performance paradigm and further evaluate the potential estrogen receptor role on the memory-evoking compound. Equally divided rats were assigned to 5 groups of sham, Aβ intrahippocampal microinjected, Pel pretreated (10 mg/kg; P.O), α estrogen antagonist intra-cerebrovascular (i.c.v.) microinjected, and β estrogen antagonist (i.c.v) microinjected animals. Intrahippocampal microinjections of Aβ were adopted to provoke AD model. Passive avoidance task test was also used to assess memory performance. Pel pretreatment prior to Aβ microinjections significantly improved step-through latency (P<0.001) in passive avoidance test. In α and β estrogen, antagonists received animals, passive avoidance task performance was not statistically changed (P=0.11 & P=0.41 respectively) compared to Pel pretreated and sham animals. Our results depicted that Pel improves Aβ induced memory dysfunction in passive avoidance test performance through estrogen receptor independently related pathways

Acute physical and psychological stress effects on visceral hypersensitivity in male rat: role of central nucleus of the amygdala

Objective: The aim of this study was to investigate the effects of acute physical and psychological stress and temporary central nucleus of the amygdala (CeA) block on stress-induced visceral hypersensitivity. Methods: Forty two male Wistar rats were used in this study. Animals were divided into 7 groups (n = 6); 1 – Control, 2 – physical stress, 3 – psychological stress, 4 – sham, 5 – lidocaine, 6 – lidocaine + physical stress and 7 – lidocaine + psychological stress. Stress induction was done using a communication box. Results: Abdominal withdrawal reflex (AWR) score was monitored one hour after stress exposure. AWR score significantly heightened at 20, 40 and 60 mmHg in the psychological stress group compared with control (p < 0.05), while, it was almost unchanged in other groups. This score was strikingly decreased at 20, 40 and 60 mmHg in lidocaine + psychological stress group compared with psychological stress with no tangible response on physical stress. Total stool weight was significantly increased in psychological stress group compared with control (0.72 ± 0.15, 0.1 ± 0.06 g) (p < 0.05), but it did not change in physical stress compared to control group (0.16 ± 0.12, 0.1 ± 0.06 g) (p < 0.05). Concomitant use of lidocaine with stress followed the same results in psychological groups (0.18 ± 0.2, 0.72 ± 0.15 g) (p < 0.05), while it did not have any effect on physical stress group (0.25 ± 0.1, 0.16 ± 0.12 g) (p < 0.05). Conclusions: Psychological stress could strongly affect visceral hypersensitivity. This effect is statistically comparable with physical stress. Temporary CeA block could also reduce visceral hypersensitivity post-acute psychological stress. Resumen: Objetivo: O objetivo desse estudo foi investigar os efeitos do estresse físico e psicológico agudo e bloqueio temporário do núcleo central da amídala (CeA) na hipersensibilidade visceral induzida por estresse. Métodos: Quarenta e dois ratos Wistar machos foram empregados nesse estudo. Os animais foram divididos em 7 grupos (n = 6): 1 – Controle, 2 – estresse físico, 3 – estresse psicológico, 4 – simulacro, 5 – lidocaína, 6 – lidocaína + estresse físico e 7 – lidocaína + estresse psicológico. A indução do estresse foi feita com o uso de uma caixa de comunicação. Resultados: O escore do reflexo de retirada abdominal (RRA) foi monitorado uma hora depois da exposição ao estresse. O escore RRA aumentou significativamente a 20, 40 e 60 mmHg no grupo de estresse psicológico versus controle (p < 0,05), enquanto que praticamente permaneceu inalterado nos demais grupos. Esse escore diminuiu drasticamente a 20, 40 e 60 mmHg no grupo de lidocaína + estresse psicológico versus estresse psicológico, sem resposta tangível no estresse físico. O peso total das fezes aumentou significativamente no grupo de estresse psicológico versus controle (0,72 ± 0,15, 0,1 ± 0,06 g) (p < 0,05), mas não houve mudança no grupo de estresse físico versus controle (0,16 ± 0,12, 0,1 ± 0,06 g) (p < 0,05). O uso simultâneo da lidocaína com o estresse acompanhou os mesmos resultados nos grupos psicológicos (0,18 ± 0,2, 0,72 ± 0,15 g) (p < 0,05), enquanto que não foi observado qualquer efeito no grupo de estresse físico (0,25 ± 0,1, 0,16 ± 0,12 g) (p < 0,05). Conclusões: O estresse psicológico pode afetar fortemente a hipersensibilidade visceral. Esse efeito é estatisticamente comparável com o estresse físico. Um bloqueio temporário do CeA também pode reduzir a hipersensibilidade visceral pós-estresse psicológico agudo. Keywords: Abdominal withdrawal reflex, Amygdala, Physical stress, Psychological stress, Visceral hypersensitivity, Palavras-chave: Reflexo de retirada abdominal, Amídala, Estresse físico, Estresse psicológico, Hipersensibilidade viscera

Trend of Blood Cholesterol Level in Iran: Results of Four National Surveys During 1991-2008

Trends in cholesterol level of different populations have been investigated in several studies. This study is conducted to determine the trend of cholesterol level of Iranian adults from 1990 to 2007. Data on cholesterol measurements of four national health surveys that have been carried out in Iran used in this study. Cholesterol level of 12728 adults aged 25-64 were measured in 1990-1 survey. Also in 1999, 2005, and 2007 surveys, blood cholesterol level of 18398, 52344 and 19630 have been sampled, respectively. The median of cholesterol were modeled with age for men and women separately for the four surveys using fractional polynomials. Then, trends in the median of cholesterol across these four surveys were studied. The analysis of cholesterol data over four national health surveys showed that the change in males' cholesterol level had a decreasing trend. This decreasing trend was more pronounced in ages younger than 45 years. However, the medians of cholesterol of females during 16 years of four national surveys had a varying trend. It was decreasing in ages younger than 45; but increasing in ages over 45 years. The median of the cholesterol level of males and females in 2005 survey was on average about 10 mg/dl higher in comparison with the other surveys. Our findings showed that the pattern of trend in cholesterol level of Iranian men and women adults have a considerable difference with those of the other developing and developed countries

Evaluation of Nanocarrier Targeted Drug Delivery of Capecitabine-PAMAM Dendrimer Complex in a Mice Colorectal Cancer Model

Capecitabine, an effective anticancer drug in colorectal cancer chemotherapy, may create adverse side effects on healthy tissues. In the present study, we first induced colon adenocarcinoma with azoxymethane, a carcinogen agent, and then investigated the potentiality of polyamidoamine (PAMAM) dendrimer to improve capecitabine therapeutic index and decrease its adverse side effects on healthy tissues like liver and bone marrow. Other variables such as nanoparticle concentrations have also been investigated. Drug loading concentration (DLC) and encapsulation efficiency (EE) were calculated for capecitabine/dendrimer complex. Experimental results showed an increase in DLC percentage resulted from elevated capecitabine/dendrimer ratio. Capecitabine/dendrimer complex could reduce tumor size and adverse side effects in comparison with free capecitabine form