Associations between gonadotropins, testosterone and ß amyloid in men at risk of Alzheimer's disease.

Testosterone and gonadotropins have been associated with cognitive decline in men and the modulation of ß amyloid (Aß) metabolism. The relatively few studies that have investigated whether changes in one or a combination of these hormones influence Aß levels have focused primarily on plasma Aß(1-40) and not on the more pathogenic Aß(1-42). Currently, no study has investigated whether these hormones are associated with an increase in brain amyloid deposition, ante mortem. Through the highly characterised Australian imaging, biomarkers and lifestyle study, we have determined the impact of these hormones on plasma Aß levels and brain amyloid burden (Pittsburgh compound B (PiB) retention). Spearman's rank correlation and linear regression analysis was carried out across the cohort and within subclassifications. Luteinizing hormone (LH) was the only variable shown, in the total cohort, to have a significant impact on plasma Aß(1-40) and Aß(1-42) levels (beta=0.163, P<0.001; beta=0.446, P<0.001). This held in subjective memory complainers (SMC) (Aß(1-40); beta=0.208, P=0.017; Aß(1-42); beta=0.215, P=0.017) but was absent in mild cognitive impairment (MCI) and Alzheimer's disease (AD) groups. In SMC, increased frequency of the APOE-ɛ4 allele (beta=0.536, P<0.001) and increasing serum LH levels (beta=0.421, P=0.004) had a significant impact on PiB retention. Whereas in MCI, PiB retention was associated with increased APOE-ɛ4 allele copy number (beta=0.674, P<0.001) and decreasing calculated free testosterone (beta=-0.303, P=0.043). These findings suggest a potential progressive involvement of LH and testosterone in the early preclinical stages of AD. Furthermore, these hormones should be considered while attempting to predict AD at these earliest stages of the disease.

Physical activity and amyloid-ß plasma and brain levels: results from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing.

Previous studies suggest physical activity improves cognition and lowers Alzheimer's disease (AD) risk. However, key AD pathogenic factors that are thought to be influenced by physical activity, particularly plasma amyloid-ß (Aß) and Aß brain load, have yet to be thoroughly investigated. The objective of this study was to determine if plasma Aß and amyloid brain deposition are associated with physical activity levels, and whether these associations differed between carriers and non-carriers of the apolipoprotein E (APOE) ε4 allele. Five-hundred and forty six cognitively intact participants (aged 60-95 years) from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing (AIBL) were included in these analyses. Habitual physical activity levels were measured using the International Physical Activity Questionnaire (IPAQ). Serum insulin, glucose, cholesterol and plasma Aß levels were measured in fasting blood samples. A subgroup (n=116) underwent (11)C-Pittsburgh compound B (PiB) positron emission tomography (PET) scanning to quantify brain amyloid load. Higher levels of physical activity were associated with higher high density lipoprotein (HDL) (P=0.037), and lower insulin (P<0.001), triglycerides (P=0.019) and Aß1-42/1-40 ratio (P=0.001). After stratification of the cohort based on APOE ε4 allele carriage, it was evident that only non-carriers received the benefit of reduced plasma Aß from physical activity. Conversely, lower levels of PiB SUVR (standardised uptake value ratio) were observed in higher exercising APOE ε4 carriers. Lower plasma Aß1-42/1-40 and brain amyloid was observed in those reporting higher levels of physical activity, consistent with the hypothesis that physical activity may be involved in the modulation of pathogenic changes associated with AD.

Intense physical activity is associated with cognitive performance in the elderly.

Numerous studies have reported positive impacts of physical activity on cognitive function. However, the majority of these studies have utilised physical activity questionnaires or surveys, thus results may have been influenced by reporting biases. Through the objective measurement of routine levels of physical activity via actigraphy, we report a significant association between intensity, but not volume, of physical activity and cognitive functioning. A cohort of 217 participants (aged 60-89 years) wore an actigraphy unit for 7 consecutive days and underwent comprehensive neuropsychological assessment. The cohort was stratified into tertiles based on physical activity intensity. Compared with individuals in the lowest tertile of physical activity intensity, those in the highest tertile scored 9%, 9%, 6% and 21% higher on the digit span, digit symbol, Rey Complex Figure Test (RCFT) copy and Rey Figure Test 30-min recall test, respectively. Statistically, participants in the highest tertile of physical activity intensity performed significantly better on the following cognitive tasks: digit symbol, RCFT copy and verbal fluency test (all P<0.05). The results indicate that intensity rather than quantity of physical activity may be more important in the association between physical activity and cognitive function.

Plasma apolipoprotein E and Alzheimer disease risk: the AIBL study of aging.

OBJECTIVE: There is mounting evidence for the contribution of apoE to the pathophysiology of Alzheimer disease (AD). Studies also indicate that plasma apoE levels may reflect disease status, suggesting that apoE is a potential AD biomarker. However, while some studies of apoE levels in plasma have presented correlations with AD pathology, others have not. Thus, there is a lack of consensus as to the suitability of plasma apoE as an AD biomarker. The major objective of this cross-sectional study was to investigate total plasma apoE as well as levels of the apoE4 form in a large, highly characterized cohort which included both healthy controls and participants with early-stage AD. METHODS: Total apoE and apoE4 were measured in 1,079 individuals drawn from the highly characterized Australian Imaging, Biomarkers and Lifestyle (AIBL) study. Total and isoform-specific plasma apoE levels were then compared with cerebral Aß load, as assessed by PET using Pittsburgh compound B (PiB). RESULTS: Total apoE and apoE4 levels were found to be significantly lower in patients with AD in the entire cohort, and decrease with Aß load in the PiB-PET subset. ApoE levels were significantly lower among ε4 homozygous individuals. In APOE ε3/ε4 heterozygote carriers, apoE4 levels decrease, indicating that apoE3 levels increase with disease. CONCLUSION: Analysis of cross-sectional data from the AIBL study indicates that plasma apoE levels are altered in AD and correlate with AD pathology level. The significance of these findings will be determined in the AIBL longitudinal study of aging.

In-situ formation of liposome of rifampicin: better availability for better treatment.

This study aimed at the preparation and characterization of preformed and in-situ formed liposomes for controlled delivery to the lungs. Two different liposome formulations were prepared and subjected to characterization of physical parameters (vesicle size, appearance, discharge rate, spray pattern and internal pressure) and drug release profile (% cumulative drug release and % drug retained). Formulations were then subjected to accelerated stability studies as per ICH guidelines. It was observed that vesicle size ranged between 2.35 +/- 0.23 - 2.41+/- 0.3 microm and 1.22 +/- 0.22- 1.34 +/- 0.15 microm respectively for preformed and in-situ formed liposomes. The discharge rate and spray area were in ranges of 110 +/- 2.4 -123 +/- 2.6 & 115+/- 2.4 -127+/-2.3 mg/ actuation & 12.5 +/-1.7 -14.1+/- 2.2 and 13.9 +/- 2.1- 14.7+/- 2.0 cm(2) respectively. In-situ liposomes showed better controlled release profile then preformed liposomes as it released 76.5+/- 2.4 - 58.5 +/- 1.8 % drug in 12 hour while retaining 23.5 +/- 1.9- 41.5 +/- 1.6 % drug whereas preformed liposomes showed cumulative release of 66.5 +/- 2.2- 84.5 +/- 2.3 % and 15.5 +/- 2.4- 33.5+/- 2.1 % fraction retained. Upon subjection to accelerated conditions for a period of 60 days, preformed liposome completely lost the objective of being controlled release formulation as they showed 92+/- 2.4 % cumulative release and only 08 +/- 1.6 % fraction retained whereas in-situ formulation showed 62 +/- 2.3 % cumulative release and 38 +/- 2.1 % fraction retained.

Anti-inflammatory and anthelmintic activities of Solanum khasianum Clarke.

In order to scientifically appraise some of the folkloric uses of Solanum khasianum Clarke (Solanaceae), the present study was undertaken to examine the anti-inflammatory and anthelmintic properties of the berries of ethanol extract. Anti-inflammatory activity was tested in carrageenan induced rat hind paw edema method at three dose level of 200, 300, and 400 mg kg(-1) respectively, Diclofenac sodium (100 mg kg(-1)) was used as the reference standard. The anti-inflammatory activity of the extract was compared with standard and control. The anthelmintic activity of the extract was tested on tape worm, liver fluke, thread worm, and hook worm using two different concentrations, 100 and 200 mg mL(-1) respectively. Time taken for the inhibition of motility was noted and compared with the standard drug, Piperazine citrate 15 mg mL. The plant extract significantly (p < 0.01) reduced the inflammation of the rats when compared to the control group. Also, the ethanol extract of the plant paralyzed the worms followed by death, which was comparable with that of the standard. This study supports the folk claim.

Transcorneal permeation of ciprofloxacin and diclofenac from marketed eye drops.

The purpose of this research was to evaluate the in vitro permeation characteristics of various marketed eye drops of ciprofloxacin (0.3% w/v aqueous solution) and diclofenac (0.1% w/v aqueous solution) through isolated goat cornea. Effect of these drugs on isolated goat eye lenses was also evaluated. Permeation studies were conducted by putting 1 ml of formulation on the cornea fixed between the donor and receptor compartments of an all glass modified Franz diffusion cell and monitoring ciprofloxacin and diclofenac concentration in the receptor (containing normal saline or bicarbonate ringer solution under continuous stirring at 37±2°) spectrophotometrically at their respective absorption maxima, after 120 min. Paired isolated goat lenses (i.e. of same animal) were used to evaluate the effect of these drugs at selected concentrations against oxidative stress (1 mM hydrogen peroxide solution). After 24 h of incubation at 37°, the lens treated with test solution (hydrogen peroxide+drug in bicarbonate ringer solution) was estimated for soluble protein content and compared with control (only hydrogen peroxide). Among marketed eye drops of ciprofloxacin, Joxin (Jawa Pharmaceuticals) showed maximum in vitro transcorneal permeation (0.558%) while I-Gesic (Centaur Pharmaceuticals) showed maximum % in vitro permeation or in vitro ocular availability among diclofenac eye drops after 120 min of permeation. The soluble protein content estimation studies revealed that these drugs at selected concentrations (permeated after 120 min.) had no deleterious effect on eye lenses rather possessed protective effect, since all formulation showed more soluble protein content when compared with control.

Characterization of hydrochloride and tannate salts of diphenhydramine.

Proper characterization is an important aspect of any dosage form design. The objective of this work was to characterize tannate salt and hydrochloride salt of diphenhydramine. As a part of characterization studies, Differential scanning calorimetry was used to investigate thermal effects and nature of salts, supported by X-ray powder diffraction. Scanning electron microphotographs was used to surface topography of salts of diphenhydramine. Fourier-transform infrared spectroscopy, solubility study and flowability studies were carried out as part of characterization. Differential scanning calorimetry and X-ray powder diffraction studies indicated amorphous nature of the tannate while hydrochloride salt has crystalline properties. Scanning electron microphotographs indicated the differences in surface topography between both the salts. Solubility studies at different pH showed pH dependant solubility of both the salts and less solubility of tannate. Stability of bulk drug at accelerated conditions of 40( degrees )/75% RH was determined for both salts. Good stability of both salts was observed.

Antioxidant and hepatoprotective activity of ethanolic and aqueous extracts of Momordica dioica Roxb. leaves.

In present study, the hepatoprotective activity of ethanolic and aqueous extracts of Momordica dioica Roxb. leaves were evaluated against carbon tetrachloride (CCl4) induced hepatic damage in rats. The extracts at dose of 200mg/kg were administered orally once daily. The substantially elevated serum enzymatic levels of serum glutamate oxaloacetate transaminase (AST), serum glutamate pyruvate transaminase (ALT), serum alkaline phosphatase (SALP) and total bilirubin were restored towards normalization significantly by the extracts. Silymarin was used as standard reference and exhibited significant hepatoprotective activity against carbon tetrachloride induced haptotoxicity in rats. The biochemical observations were supplemented with histopathological examination of rat liver sections. The results of this study strongly indicate that Momordica dioica Roxb. leaves have potent hepatoprotective action against carbon tetrachloride induced hepatic damage in rats. Ethanolic extract was found more potent hepatoprotective. Meanwhile, in vivo antioxidant and free radical scavenging activities were also screened which were positive for both ethanolic and aqueous extracts. This study suggests that possible mechanism of this activity may be due to free radical-scavenging and antioxidant activities which may be due to the presence of flavonoids in the extracts.

A comparative study of air pollution in Indian cities.

Rapid and unplanned industrialization and urbanization has resulted in the deterioration of India's air quality according to air-quality monitoring carried out in seven major Indian cities in industrial and residential areas between 1995 and 2000. Suspended particulate matter (SPM) levels in Indian cities are in the range 50 to 550 microg/m(3). NO(x) values are high in Delhi's residential areas, with values of 33 microg/m(3) in 1995 and 34.6 microg/m(3) in 2000, while in an industrial area values of 29.4 microg/m(3) were found in 1995, increasing to 33.7 microg/m(3) in 2000. SO(2) values are very high in Pune city, ranging from 43.3 microg/m(3) in residential to 43.69 microg/m(3) in an industrial area in 2000.

Externalizing behaviors and television viewing in children of low-income minority parents.

The parents of 151 children, ages 4-16 years, attending the pediatric outpatient clinic of an urban hospital were surveyed to determine if aggressive behavior among children of low literacy and low-income parents is related to excessive television viewing or to sociological variables such as ethnicity/race, education, occupation, and parents' marital status. The survey consisted of 22 questions about the ethnicity, marital status, education, and occupation of the parent, the television viewing behavior of the child, and the externalizing behavior scale of the Child Behavior Checklist of Achenbach (CBC). The television viewing habits of children in this study were not significantly different from viewing habits reported in national surveys of the US population. T scores in the aggression scale of CBC were unrelated to the hours of television watched by children and the control of viewing by the parent but were significantly associated with the employment and marital status of the mother. Children of unemployed and single mothers had higher externalizing-behavior scores, suggesting that family ecological variables may have more influence on children's behavior than the duration of television viewing.