Effects of soya bean extract, bisphenol A and 17 beta-estradiol on the testis and circulating levels of testosterone and estradiol among peripubertal juvenile male sprague-dawley rats

In this study, juvenile male Sprague-Dawley rats (PND 22) were fed with soya extract, bisphenol A, and 17 beta-estradiol, respectively by oral gavage to determine the potential effect on the morphology of their reproductive organs and their hormonal levels. After three weeks of treatment (PND 43), all animals were sacrificed and the blood and testes were collected. All the three treatment groups showed histological differences in testes morphology compared to the control. Animals treated with soya extract and bisphenol A showed a decrease in circulating estradiol levels while animals treated with 17 beta-estradiol showed elevated circulating levels of estradiol. Only the animals treated with soya extract showed elevated levels of circulating testosterone. The results of the present study showed that, soya extract, bisphenol A, and 17 beta-estradiol can alter the histological structure of the testes and influence circulating steroidal hormone levels

Renal targeting potential of a polymeric drug carrier, poly-L-glutamic acid, in normal and diabetic rats

Background and purpose: Poly-l-glutamic acid (PG) has been used widely as a carrier to deliver anticancer chemotherapeutics. This study evaluates PG as a selective renal drug carrier. Experimental approach: 3H-deoxycytidine-labeled PGs (17 or 41 kDa) and 3H-deoxycytidine were administered intravenously to normal rats and streptozotocin-induced diabetic rats. The biodistribution of these compounds was determined over 24 h. Accumulation of PG in normal kidneys was also tracked using 5-(aminoacetamido) fluorescein (fluoresceinyl glycine amide)-labeled PG (PG-AF). To evaluate the potential of PGs in ferrying renal protective anti-oxidative stress compounds, the model drug 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) was conjugated to 41 kDa PG to form PG-AEBSF. PG-AEBSF was then characterized and evaluated for intracellular anti-oxidative stress efficacy (relative to free AEBSF). Results: In the normal rat kidneys, 17 kDa radiolabeled PG (PG-Tr) presents a 7-fold higher, while 41 kDa PG-Tr shows a 15-fold higher renal accumulation than the free radiolabel after 24 h post injection. The accumulation of PG-AF was primarily found in the renal tubular tissues at 2 and 6 h after an intravenous administration. In the diabetic (oxidative stress-induced) kidneys, 41 kDa PG-Tr showed the greatest renal accumulation of 8-fold higher than the free compound 24 h post dose. Meanwhile, the synthesized PG-AEBSF was found to inhibit intracellular nicotinamide adenine dinucleotide phosphate oxidase (a reactive oxygen species generator) at an efficiency that is comparable to that of free AEBSF. This indicates the preservation of the anti-oxidative stress properties of AEBSF in the conjugated state. Conclusion/Implications: The favorable accumulation property of 41 kDa PG in normal and oxidative stress-induced kidneys, along with its capabilities in conserving the pharmacological properties of the conjugated renal protective drugs, supports its role as a potential renal targeting drug carrier

Renal targeting potential of a polymeric drug carrier, poly-L-glutamic acid, in normal and diabetic rats

Hann-Juang Chai,1 Lik-Voon Kiew,1 Yunni Chin,1 Anwar Norazit,2 Suzita Mohd Noor,2 Yoke-Lin Lo,3,4 Chung-Yeng Looi,1 Yeh-Siang Lau,1 Tuck-Meng Lim,5 Won-Fen Wong,6 Nor Azizan Abdullah,1 Munavvar Zubaid Abdul Sattar,7 Edward J Johns,8 Zamri Chik,1 Lip-Yong Chung3 1Department of Pharmacology, 2Department of Biomedical Science, 3Department of Pharmacy, Faculty of Medicine, University of Malaya, 4School of Pharmacy, International Medical University, Kuala Lumpur, 5Department of Chemical Science, Faculty of Science, Universiti Tunku Abdul Rahman, Kampar, 6Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, 7School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Malaysia; 8Department of Physiology, University College Cork, Cork, Republic of Ireland Background and purpose: Poly-L-glutamic acid (PG) has been used widely as a carrier to deliver anticancer chemotherapeutics. This study evaluates PG as a selective renal drug carrier.Experimental approach: 3H-deoxycytidine-labeled PGs (17 or 41 kDa) and 3H-deoxycytidine were administered intravenously to normal rats and streptozotocin-induced diabetic rats. The biodistribution of these compounds was determined over 24 h. Accumulation of PG in normal kidneys was also tracked using 5-(aminoacetamido) fluorescein (fluoresceinyl glycine amide)-labeled PG (PG-AF). To evaluate the potential of PGs in ferrying renal protective anti-oxidative stress compounds, the model drug 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) was conjugated to 41 kDa PG to form PG-AEBSF. PG-AEBSF was then characterized and evaluated for intracellular anti-oxidative stress efficacy (relative to free AEBSF).Results: In the normal rat kidneys, 17 kDa radiolabeled PG (PG-Tr) presents a 7-fold higher, while 41 kDa PG-Tr shows a 15-fold higher renal accumulation than the free radiolabel after 24 h post injection. The accumulation of PG-AF was primarily found in the renal tubular ­tissues at 2 and 6 h after an intravenous administration. In the diabetic (oxidative stress-induced) kidneys, 41 kDa PG-Tr showed the greatest renal accumulation of 8-fold higher than the free compound 24 h post dose. Meanwhile, the synthesized PG-AEBSF was found to inhibit intracellular nicotinamide adenine dinucleotide phosphate oxidase (a reactive oxygen species generator) at an efficiency that is comparable to that of free AEBSF. This indicates the preservation of the anti-oxidative stress properties of AEBSF in the conjugated state.Conclusion/Implications: The favorable accumulation property of 41 kDa PG in normal and oxidative stress-induced kidneys, along with its capabilities in conserving the pharmacological properties of the conjugated renal protective drugs, supports its role as a potential renal targeting drug carrier. Keywords: carboxylated polymers, carboxylated polypeptides, carrier, diabetes, renal drug delivery, acute kidney injury, chronic renal failure, end-stage renal failur

Rural villages as socially urban spaces in Malaysia

10.1080/00420980412331297573Urban Studies41122357-237

The role of astrocytes in parkinson\u27s disease

2014 Springer International Publishing Switzerland. All rights reserved. Unlike other disorders, astrocytes in regions undergoing neurodegeneration in patients with Parkinson\u27s disease do not become reactive. Instead gray matter protoplasmic astrocytes accumulate α-synuclein, withdraw their processes from damaged neurons, and show altered expression of constituent proteins, including PINK-1, parkin, and DJ-1 (gene products associated with recessive Parkinson\u27s disease). These and other gene products are normally up-regulated in astrocytes by disease states. Combined, these data suggest that protoplasmic astrocytes lose their protective function in patients with Parkinson\u27s disease, leaving neurons vulnerable to perturbations and insults they would normally be protected from. Recent work also shows that astrocytes are able to take up and metabolize L-DOPA, the drug of choice for standard therapy for Parkinson\u27s disease. It is therefore possible that ongoing astrocytic dysfunction may compromise the efficacy of L-DOPA therapy. These unique astrocytic responses to the disease process and current main therapy support the concept that astrocytes play a critical, under-recognized role in the initiation, progression, and treatment response of patients with Parkinson\u27s disease