Deleterious effects of potassium bromate administration on renal and hepatic tissues of Swiss mice

Potassium bromate (KBrO₃) is widely used as a food additive and is a major water disinfection by-product. The present study reports the side effects of KBrO₃ administration in Swiss mice. Animals were randomly divided into three groups: control, low dose KBrO₃ (100 mg/kg/day) and high dose KBrO₃ (200 mg/kg/day) groups. Administration of KBrO₃ led to decreased white blood corpuscles (WBCs), red blood corpuscles (RBCs) and platelets count in the animals of both the high and the low dose groups. Altered lipid profile represented as low density lipoprotein (LDL), high density lipoprotein (HDL) and cholesterol levels were observed in plasma samples of both KBrO₃ treated groups of mice. Also, an increased plasma level of LDH was detected in both KBrO₃ treated groups. Histological investigations showed impaired renal and hepatic histology that was concomitant with increased plasma Creatinine level in both of KBrO₃-treated groups. Nevertheless, decreased glutathione (GSH) level in both renal and hepatic tissue of mice after KBrO₃ intake was detected. These results show that KBrO₃ has serious damaging effects and therefore, its use should be avoided.     

SARS-CoV-2 associated COVID-19 in geriatric population: A brief narrative review

Coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has emerged as a fatal pandemic and has crushed even the world’s best healthcare systems. Globally, it has affected 40,373,228 individuals and resulted in 1,119,568 deaths as of October 19, 2020. Research studies have demonstrated that geriatric population is vastly vulnerable to COVID-19 morbidity and mortality given their age and preexisting chronic comorbidities such as cardiovascular disease, hypertension, diabetes mellitus, chronic pulmonary and chronic kidney disease The data regarding susceptibility of elderly population to COVID-19 is accruing and suggests that factors like age, gender, chronic comorbidity, inflammaging, immunosenescence and renin angiotensin system may be the contributing risk factors towards COVID-19 and associated mortality in elderly population. Based on updated scientific literature, this narrative review précises the clinical presentations and underlying risk factors that might be associated with COVID-19 morbidity in geriatric population and provides informed insights, and discusses clinical presentation, psychosocial impact, mortality and potential corticosteroid treatment and prevention strategies of COVID-19 in older adults.     

Murine Double Minute 2 Gene (MDM2) rs937283A/G variant significantly increases the susceptibility to breast cancer in Saudi Women

Breast cancer is predominant causes of mortality in women worldwide. Genetic polymorphisms have a significant role in breast cancer aetiology. TP53 and its inhibitor the murine double minute 2 (MDM2) genes encode proteins that have crucial functions in the DNA damage response. The allelic variations within these genes could influence the susceptibility to breast cancer. MDM2 promotor polymorphism rs937283A/G has a role in susceptibility to cancer and modifies the promoter activity. In the present case-control study, the association of MDM2 rs937283A/G polymorphism and breast cancer susceptibility in Saudi women with samples of 137 breast cancer patients, and 98 healthy controls were explored. MDM2 gene polymorphism rs937283A/G was genotyped by polymerase chain reaction restriction fragment length polymorphism and confirmed by sequencing. The results revealed that rs937283A/G variant is significantly increases the risk of breast cancer in Saudi women (p-value = 0.0078). Moreover, rs937283A/G polymorphism was associated with high risk of breast cancer in estrogen positive breast cancer patients (p-value = 0.0088), progesterone positive breast cancer patients (p-value = 0.0043), human epidermal growth factor receptor 2 negative breast cancer patients (p-value = 0.0026), and triple negative breast cancer patients where (p-value = 0.0003). Positive association between increased breast cancer risk and rs937283 variant in premenopausal Saudi women, below 50 years of age, was demonstrated (p-value = 0.0023). Collectively, MDM2 rs937283A/G polymorphism could act as a possible biomarker for breast cancer susceptibility in Saudi women.     

The association between overweight/obesity and psychological distress: A population based cross-sectional study in Saudi Arabia

ObjectivesThe objective of this study was to compare the association between mental well-being between obese (classes 1 and 2), over-weight and non-obese population-based individualsMethodsA population-based cross-sectional study was conducted in Al-Kharj, Saudi Arabia. A total of 1019 Saudi nationals aged ≥ 18 years participated in the survey. BMI scores were used to categorize participants into three groups: Obese, overweighted and non-obese/non-overweight. Mental well-being was evaluated by using the validated Arabic version of the General Health Questionnaire version 12 (GHQ-12).ResultsWe used total GHQ score (Mean=12; SD=5.23) to compare mental well-being between the four BMI class categories. The overall one-way ANOVA model was statistically significant (F = 7.018, d = 6, P < 0.001). In multivariate analysis, after adjusting for sociodemographic variables, diabetes and smoking statuses we found that higher psychological distress (as evident by a higher total GHQ score) was associated with higher BMI. The unstandardized Beta regression coefficient = 2.627; P = 0.034). Females were more likely to have higher psychological distress than males (unstandardized Beta = 1.466, P = 0.003). Job status whether being unemployed or ‘civilian’ (civil worker) was significantly associated with higher psychological distress (unstandardized Beta = 1.405, P = 0.041). Being diabetic has a 1.6 times higher risk of psychological distress (unstandardized Beta = 1.604, P = 0.027).ConclusionThe study highlights the public health implications of psychological distress amongst individuals with overweight and obesity in Saudi Arabia. Future longitudinal studies should explore the temporality of this relationship.     

Structure-Activity Relationship Studies of N- and C-Terminally Modified Secretin Analogs for the Human Secretin Receptor

The pleiotropic role of human secretin (hSCT) validates its potential use as a therapeutic agent. Nevertheless, the structure of secretin in complex with its receptor is necessary to develop a suitable therapeutic agent. Therefore, in an effort to design a three-dimensional virtual homology model and identify a peptide agonist and/or antagonist for the human secretin receptor (hSR), the significance of the primary sequence of secretin peptides in allosteric binding and activation was elucidated using virtual docking, FRET competitive binding and assessment of the cAMP response. Secretin analogs containing various N- or C-terminal modifications were prepared based on previous findings of the role of these domains in receptor binding and activation. These analogs exhibited very low or no binding affinity in a virtual model, and were found to neither exhibit in vitro binding nor agonistic or antagonistic properties. A parallel analysis of the analogs in the virtual model and in vitro studies revealed instability of these peptide analogs to bind and activate the receptor.     

Cortical activation changes during repeated laser stimulation: a magnetoencephalographic study

Repeated warm laser stimuli produce a progressive increase of the sensation of warmth and heat and eventually that of a burning pain. The pain resulting from repetitive warm stimuli is mediated by summated C fibre responses. To shed more light on the cortical changes associated with pain during repeated subnoxious warm stimulation, we analysed magnetoencephalographic (MEG) evoked fields in eleven subjects during application of repetitive warm laser stimuli to the dorsum of the right hand. One set of stimuli encompassed 10 laser pulses occurring at 2.5 s intervals. Parameters of laser stimulation were optimised to elicit a pleasant warm sensation upon a single stimulus with a rise of skin temperature after repeated stimulation not exceeding the threshold of C mechano-heat fibres. Subjects reported a progressive increase of the intensity of heat and burning pain during repeated laser stimulation in spite of only mild (4.8°C) increase of skin temperature from the first stimulus to the tenth stimulus. The mean reaction time, evaluated in six subjects, was 1.33 s, confirming involvement of C fibres. The neuromagnetic fields were modelled by five equivalent source dipoles located in the occipital cortex, cerebellum, posterior cingulate cortex, and left and right operculo-insular cortex. The only component showing statistically significant changes during repetitive laser stimulation was the late component of the contralateral operculo-insular source peaking at 1.05 s after stimulus onset. The amplitude increases of the late component of the contralateral operculo-insular source dipole correlated with the subjects' numerical ratings of warmth and pain. Results point to a pivotal role of the contralateral operculo-insular region in processing of C-fibre mediated pain during repeated subnoxious laser stimulation.     

Effects of the perinatal exposure of Gum Arabic on the development,behavior and biochemical parameters of mice offspring

The effects of the perinatal oral exposure to Gum Arabic (GA) on mice offspring was examined. GA was added to the drinking water of pregnant female Swiss–Webster strain mice at doses of 1 and 4 g/kg body weight, starting from the first day of pregnancy. The treatment continued until the fifteenth day after delivery, after which mothers were switched to plain tap water. A number of tests were carried out on offspring starting one day after birth and extending up to postnatal day 30 (PD30). Pups showed a reduced gain of body weight and delayed opening of the eyes in comparison to the control group and only pups exposed to 1 g/kg body weight GA had a faster appearance of hair. Sensory motor reflex tests carried out during the weaning period (from day of birth to PD21) showed enhanced motor reflexes in pups exposed to GA. During the adolescent period (from PD22 to PD30), offspring showed dose-dependent enhanced motor activity (on PD22), reduced anxiety and fear (on PD27) and slightly enhanced memory and learning abilities (on PD30). Biochemical tests of a number of blood parameters were conducted during and after the weaning period (on PD15 and PD30, respectively). Our results indicated that GA might have a hypoglycemic and a beneficial effect on red and white blood cell counts. This study gives a first insight on the effect of GA consumption on offspring, providing a starting point for further studies.     

Neurobehavioral changes in mice offspring induced by prenatal exposure to acute toxicity of sodium selenite

Selenium is an essential element with a narrow margin between beneficial and toxic effects. This study was aimed to determine the neurobehavioral changes resulted from the prenatal exposure of mice to high doses of sodium selenite during fetal and early postnatal development. Atomic absorption for monitoring the placental transfer of selenium to offspring was employed. The developmental observations as well as the behavioral tests, such as sensory motor reflexes, and learning and memory test in automatic reflex conditioner (shuttle box) (active avoidance responses) were applied. Adult mice was assigned into three groups: the first group was remained as a control group given phosphate buffered saline; the second and the third groups were orally administrated sodium selenite at doses of 1 mg/kg and 4 mg/kg of the diet, respectively started from the 7^th day to the end of the gestation period. Appearance of body hair and opening of eyes of the pups from treated mothers were delayed in a dose-dependent manner. The body weight gain came significantly lower than those of the control especially at the higher dose. Selenite also inhibited the sensory motor reflexes in all elements of acts and postures in a dose dependent manner. The active avoidance training-test indicated that selenite exposure was associated with learning impairment. Acetylcholine recorded a significant decrease in almost all the period of this study. By using atomic absorption, we found a significant high concentration of selenium in the brain, liver and kidney until the 40^th postnatal day, indicating active transfer of selenium from mothers to embryos.