Azza Hassan

Brain aging in a sample of normal Egyptians cognition, education, addiction and smoking

The impact of duration of education, cannabis addiction and smoking on cognition and brain aging is studied in 211 normal Egyptian volunteers with mean age 46.4+/-3.6 years (range: 20-76 years). Subjects were classified into two groups: Gr I (non-addicts) with 174 subjects, mean age 49.9+/-3.8 years (range 20-76 years), smokers and non-smokers, educated and non-educated and Gr II (cannabis addicts) with 37 subjects, mean age 43.6+/-2.6 years (range 20-72 years) all smokers, educated and non-educated. Outcome measures included the Paced Auditory Serial Addition test (PASAT) for testing attention and the Trailmaking test A, and B (TMa and TMb) for testing psychomotor performance. Age correlated positively with score of Trailmaking test (TMb) in the non-addict group and in the addict group (TMa and TMb). Years of education correlated negatively with scores of Trialmaking test (TMb) in the non-addict group (Gr I) but not the addict group (Gr II). However, in both groups mean scores of the Trailmaking test (TMa) were significantly lower in subjects with a primary level of education than those with higher levels of education. No significant difference was detected between male smokers and nonsmokers of Gr I (non-addicts) regarding any of the neuropsychological tests. Yet, smokers and the non-educated group had poorer attention compared to non-smokers of the same group. Cannabis addicts (Gr II) had significantly poorer attention than non-addict normal volunteers (Gr I). It is concluded that impairment of psychomotor performance is age related whether in normal non-addicts or in cannabis addicts. A decline in attention was detected in cannabis addicts and has been considered a feature of pathological aging. Education in early life as well as the duration of education are neuroprotectors for brain aging more so in the non-addict than addict group. Though cigarette smoking per se has no effect on cognitive abilities in normal aging, it becomes evident that its association with lack of education impairs attention.

Parkinson's disease, cognition and aging Clinical, neuropsychological, electrophysiological and cranial computerized tomographic assessment

Forty-three patients with Parkinsons disease (PD) and thirty-seven normal volunteers were subjected to clinical, neuropsychological, neurophysiological (P300 component of the event-related potentials ERP) and radiological (cranial computerized tomographic scanning CCT) evaluation. Intentional memory was more impaired in PD than in normal controls, more so in the demented group of patients, and was related to enlargement of third ventricular size in CCT. While intentional memory was age related in PD patients, perception was age-related in normal controls. Neither global nor specific cognitive functions were related to duration, severity of parkinsonian motor disability, or depression. However, depression in PD was significantly related to parkinsonian motor disability. P300 latency was more prolonged in PD patients than normal controls. P300 parameters of PD patients were not influenced by age, cognitive functions, duration or severity of motor disability, or depression. The reaction time was the only P300 parameter that was age-related in normal controls. Subcortical atrophy as indicated by CCT was more marked in PD and correlated with age in both patients and controls. Subcortical atrophy was significantly related to cognitive functions in PD but not in normal controls. It was concluded that cognitive impairment in PD could be attributed to complex cognitive changes rather than age. It is a disease process, though not directly related to parkinsonian motor disability or depression. PD differed from normal aging as regards the effect of age on the specific cognitive functions, where in PD patients, age was related to intentional memory, yet in normal controls, it was related to perception. Intentional memory deterioration was found to be specific of PD, being related to subcortical atrophy as well as being more pronounced in the demented group of patients.

Renoprotective Effect of Lactoferrin against Chromium-Induced Acute Kidney Injury in Rats: Involvement of IL-18 and IGF-1 Inhibition

Hexavalent chromium (CrVI) is a heavy metal widely used in more than 50 industries. Nephrotoxicity is a major adverse effect of chromium poisoning. The present study investigated the potential renoprotective effect of lactoferrin (Lf) against potassium dichromate (PDC)-induced acute kidney injury (AKI) in rats. Beside, because previous studies suggest that interlukin-18 (IL-18) and insulin-like growth factor-1 (IGF-1) play important roles in promoting kidney damage, the present work aimed to evaluate the involvement of these two cytokines in PDC model of AKI and in the potential renoprotective effect of lactoferrin. Adult male albino Wistar rats were pretreated with Lf (200mg/kg/day, p.o.) or (300mg/kg/day, p.o.); the doses that are usually used in the experiment studies, for 14 days followed by a single dose of PDC (15mg/kg, s.c.). PDC caused significant increase in serum urea, creatinine, and total protein levels. This was accompanied with decreased renal glutathione content, and increased renal malondialdehyde, IL-18, IL-4, nuclear factor kappa B (NFκB), IGF-1, and the phosphorylated form of forkhead box protein O1 (FoxO1) levels. Moreover, normal expression IFN-γ mRNA and enhanced expression of TNF-α mRNA was demonstrated in renal tissues. Histopathological investigations provoked deleterious changes in the renal tissues. Tubular epithelial hyperplasia and apoptosis were demonstrated immunohistochemically by positive proliferating cell nuclear antigen (PCNA), Bax, and Caspase-3 expression, respectively. Pretreatment of rats with Lf in both doses significantly corrected all previously mentioned PDC-induced changes with no significant difference between both doses. In conclusion, the findings of the present study demonstrated the involvement of oxidative stress, inflammatory reactions, tubular hyperplasia and apoptosis in PDC-induced AKI. It suggested a role of IL-18 through stimulation of IL-4-induced inflammatory pathway, and IGF-1 through triggering FoxO1-induced cell proliferation. Moreover, the study revealed that Lf protected the kidney against Cr-induced AKI in rats and significantly showed antioxidant, anti-inflammatory, and anti-proliferative properties with down-regulation of IL-18 and IGF-1.

Hemorheology, stroke and the elderly.

Whole blood filterability was measured in 53 stroke patients (28 patients 40-60 yr and 25 patients greater than 60 yr) to study the hemorheologic parameters, stressing the changes occurring in the elderly. A negative linear correlation was found between whole blood filterability and the hematocrit, plasma viscosity and the serum level of macroproteins (alpha 2-globulin, gamma-globulin and fibrinogen), indicating that whole blood filterability is a collective measure of the different hemorheologic parameters. Whole blood filterability was significantly reduced in stroke patients as compared to normal control values. This reduction could not be attributed to a difference in hematocrit or plasma viscosity, which emphasizes the role of red cell deformability in the filterability of blood of stroke patients. Moreover, whole blood filterability was significantly lower in stroke patients more than 60 yr old than in stroke patients less than 60 yr old. Both plasmatic and red cell factors were contributing factors in the reduction of filterability in the elderly.

Brain aging in normal Egyptians: Neuropsychological, electrophysiological and cranial tomographic assessment

Eighty-eight normal Egyptian volunteers above the age of 40 years were studied for brain aging and subjected to neuropsychological (the Paced Auditory Serial Addition Test; the Trailmaking test A, B; the Digit Symbol Substitution Test; sensory and secondary memory tests), electrophysiological (computerized EEG, P300 and reaction time measures), and Computerized Cranial Tomography (CCT) assessment. A significant correlation was found between age and both perception (Digit Symbol Substitution Test (DDST) and psychomotor performance (Trailmaking B test (TMb)), reaction time (RT) and the size of the third ventricle. Whereas females were worse in attention (Paced Auditory Serial Addition Test (PASAT)), males had worse performance in secondary memory test. Elderly subjects with vascular risk factors did worse in psychomotor performance (TMa) than subjects with no risk factors. Non-educated subjects showed worse perception (DSST) than educated subjects. A significant decrease in upper and lower limit percent power of the alpha band was found in subjects above 60 years, males, and non-educated subjects. A significant increase in theta activity was found only in non-educated subjects. It is concluded that decline in specific cognitive functions occurs with advancing age. Vascular risk factors and lack of education early in life enhance these changes. Moreover, the EEG slowing in the elderly was linked to lack of education early in life.

Lactoferrin enhanced apoptosis and protected against thioacetamide-induced liver fibrosis in rats.

BACKGROUND: Liver fibrosis is the common pathologic consequence of all chronic liver diseases. AIM: Lactoferrin (Lf) was investigated for its possible hepatoprotective effect against thioacetamide (TAA)-induced liver fibrosis rat model. MATERIAL AND METHODS: Rats received TAA (200 mg/kg/biweekly, ip) for four successive weeks. Lf (200 mg/kg/day, p.o.) or vehicle (VHC) was administered for one month before and another month during TAA injection. Body weight and mortality rate were assessed during the month of TAA-intoxication. Thereafter, serum and liver tissues were analyzed for liver function, oxidative, fibrotic and apoptotic markers. RESULTS: Lf conserved rats against TAA-induced body weight-loss and mortality. Preservation of serum albumin, alkaline phosphatase and total bilirubin levels was also observed. Lf also protected rats against TAA-induced decrease in reduced glutathione and increase in malondialdehyde liver contents. Normal liver contents of hydroxyproline, nuclear factor kappa B and alpha fetoprotein; as markers of fibrosis; were increased with TAA and conserved with Lf-TAA. Lf maintained the normal architecture of the liver and immunohistochemical findings revealed increase in apoptotic bodies compared to TAA that favored necrosis. CONCLUSION: In conclusion, Lf improved liver function, reduced oxidative stress and liver fibrosis, and enhanced apoptosis in rats with liver fibrosis, suggesting it to have useful therapeutic potential in patients with liver fibrosis.

Cilostazol attenuates indices of liver damage induced by thioacetamide in albino rats through regulating inflammatory cytokines and apoptotic biomarkers

Abstract Even though cilostazol was assessed before in several models of atherosclerosis, so far its full systematic effect as a natural anti‐inflammatory and anti‐apoptotic mediator in the protection of liver damage and complication has not been fully clarified, which is the target of this study. For that purpose, we examined the protective effect of cilostazol (10 and 5 mg/kg, p.o. b.wt.) in an acute hepatic injury model by orally injecting it for 3 weeks prior to a single dose of TAA (300 mg/kg, i.p) injection. Ursodeoxycholic acid was used as a standard drug (50 mg/kg, p.o. b.wt.). After injection of thioacetamide by 48hr, rats were sacrificed. On the serum biochemical level, cilostazol ameliorated the thioacetamide consequence, where it presented a significant enhancement in the liver enzymes activities [Aspartate aminotransferase (AST) & Alanine aminotransferase (ALT)]. On the other hand, at the tissue level (Liver), it revealed a significant improvement in pro‐inflammatory cytokines [Tumor necrosis factor alpha (TNF‐&agr;), Interleukin 1 beta (IL‐1&bgr;), Nuclear factor kappa B (NF‐&kgr;B), NF‐&kgr;B (P65/P50 nucleus translocation), caspase‐3, cleaved caspase‐3 & C‐reactive protein (CRP)], redox level [Reduced glutathione (GSH) & Malondialdehyde (MDA)], histopathological findings, Reverse transcription polymerase chain reaction (RT‐PCR) analysis (expression of TNF‐&agr; and NF‐&kgr;B mRNA levels), and immunohistochemical reaction (caspase‐3 & TNF‐&agr;). Obviously, the high dose of cilostazol (10 mg/kg, p.o. b.wt.) displayed a more pronounced effect than its lower one and nearly equal to ursodeoxycholic acid in the most of the parameters. These results give a new awareness into the hopeful molecular mechanisms by which cilostazol attenuates several factors participated in the progression of liver damage.

Involvement of insulin resistance in D-galactose-induced age-related dementia in rats: Protective role of metformin and saxagliptin

Age-related dementia is one of the most devastating disorders affecting the elderly. Recently, emerging data suggest that impaired insulin signaling is the major contributor in the development of Alzheimer’s dementia (AD), which is the most common type of senile dementia. In the present study, we investigated the potential therapeutic effects of metformin (Met) and saxagliptin (Saxa), as insulin sensitizing agents, in a rat model of brain aging and AD using D-galactose (D-gal, 150 mg/kg/day, s.c. for 90 successive days). Six groups of adult male Wistar rats were used: normal, D-gal, Met (500 mg/kg/day, p.o), and Saxa (1 mg/kg/day, p.o) control groups, as well as D-gal/Met and D-gal/Sax treated groups. Impaired learning and memory function was observed in rats treated with D-gal using Morris water maze test. Biochemical and histopathological findings also revealed some characteristic changes of AD in the brain that include the increased content of acetylcholine, glutamate, and phosphorelated tau, as well as deposition of amyloid plaques and neurofibrillary tangles. Induction of insulin resistance in experimentally aged rats was evidenced by increased blood glycated hemoglobin, brain contents of insulin and receptors for advanced glycated end-products, as well as decreased brain insulin receptor level. Elevation of oxidative stress markers and TNF-α brain content was also demonstrated. Met and Saxa, with a preference to Met, restored the normal memory and learning functions in rats, improved D-gal-induced state of insulin resistance, oxidative stress and inflammation, and ameliorated the AD biochemical and histopathological alterations in brain tissues. Our findings suggest that D-gal model of aging results in a diminishing of learning and memory function by producing a state of impaired insulin signaling that causes a cascade of deleterious events like oxidative stress, inflammation, and tau hyper-phosphorylation. Reversing of these harmful effects by the use of insulin-sensitizing drugs like Met and Saxa suggests their involvement in alleviation insulin resistance as the underlying pathology of AD and hence their potential use as anti-dementia drugs.

Intranasal Chromium Induces Acute Brain and Lung Injuries in Rats: Assessment of Different Potential Hazardous Effects of Environmental and Occupational Exposure to Chromium and Introduction of a Novel Pharmacological and Toxicological Animal Model.

Chromium (Cr) is used in many industries and it is widely distributed in the environment. Exposure to Cr dust has been reported among workers at these industries. Beside its hazardous effects on the lungs, brain injury could be induced, as the absorption of substances through the nasal membrane has been found to provide them a direct delivery to the brain. We investigated the distribution and the effects of Cr in both brain and lung following the intranasal instillation of potassium dichromate (inPDC) in rats. Simultaneously, we used the common intraperitoneal (ipPDC) rat model of acute Cr-toxicity for comparison. Thirty male Wistar rats were randomly allocated into five groups (n = 6); each received a single dose of saline, ipPDC (15 mg/kg), or inPDC in three dose levels: 0.5, 1, or 2 mg/kg. Locomotor activity was assessed before and 24 h after PDC administration, then, the lungs and brain were collected for biochemical, histopathological, and immunohistochemical investigations. Treatment of rats with ipPDC resulted in a recognition of 36% and 31% of the injected dose of Cr in the brain and lung tissues, respectively. In inPDC-treated rats, targeting the brain by Cr was increased in a dose-dependent manner to reach 46% of the instilled dose in the group treated with the highest dose. Moreover, only this high dose of inPDC resulted in a delivery of a significant concentration of Cr, which represented 42% of the instilled dose, to the lungs. The uppermost alteration in the rats locomotor activity as well as in the brain and lung histopathological features and contents of oxidative stress biomarkers, interleukin-1β (IL-1β), phosphorylated protein kinase B (PKB), and cyclooxygenase 2 (COX-2) were observed in the rats treated with inPDC (2 mg/kg). The findings revealed that these toxic manifestations were directly proportional to the delivered concentration of Cr to the tissue. In conclusion, the study showed that a comparably higher concentrations of Cr and more elevated levels of oxidative stress and inflammatory markers were observed in brain and lung tissues of rats subjected to inPDC in a dose that is just 0.13 that of ipPDC dose commonly used in Cr-induced toxicity studies. Therefore, the study suggests a high risk of brain-targeting injury among individuals environmentally or occupationally exposed to Cr dust, even in low doses, and an additional risk of lung injury with higher Cr concentrations. Moreover, the study introduces inPDC (2 mg/kg)-instillation as a new experimental animal model suitable to study the acute brain and lung toxicities induced by intranasal exposure to Cr compounds.