Safety and immunogenicity of an HIV subtype B and E prime-boost vaccine combination in HIV-negative Thai adults

ALVAC-HIV (vCP1521) and AIDSVAX B/E were evaluated in a phase 1/2 trial of human immunodeficiency virus (HIV)-negative Thai adults. Of 133 volunteers enrolled, 122 completed the trial. There were no serious vaccine-related adverse events, nor were there intercurrent HIV infections. Lymphoproliferative responses to glycoprotein 120 E were induced in 63% of the volunteers, and HIV-specific CD8 cytotoxic T lymphocyte responses were induced in 24%. Antibody responses increased in frequency and magnitude in association with the dose level of AIDSVAX B/E. Binding and neutralizing antibodies to the MN strain were induced in 100% and 98%, respectively, of the volunteers receiving 600 microg of AIDSVAX B/E, and such antibodies to E strains were induced in 96% and 71%, respectively, of these volunteers. This vaccine combination was well tolerated and was immunogenic, meeting milestones for advancement to phase 3 evaluation.     

Occupational exposure of Sri Lankan tea plantation workers to paraquat.

Absorption of the herbicide paraquat (1,1''-dimethyl-4,4''-bipyridinium) by mixer-loaders and spray operators on a Sri Lankan tea plantation was assessed over five consecutive days of spraying. Beginning on the day before spraying started and continuing for each of the five spraying days and for seven days after the last day of spraying, 24-hour urine samples were collected from each of the workers. Potential dermal exposure was assessed during further applications of paraquat on the day after the last day of urine collection. For this purpose two spraying replicates were conducted that involved the handling or spraying of an amount of paraquat equivalent to the maximum used per day in the assessment of absorption. The mixer-loaders and spray operators incurred, on average, approximately equivalent amounts of potential dermal exposure (66 mg and 74 mg paraquat ion, resp.); however, the distribution of the exposure differed. About 86% of the total exposure experienced by the mixer-loaders was to the hands, whereas about 90% of the exposure of the spray operators involved their hands, legs, and feet, in approximately equal proportions. In both cases, 90% or more of the total potential exposure involved parts of the body that were normally uncovered. Despite the evidence of dermal exposure, no paraquat was detected in the workers'' urine. This probably was due to the very low concentration of paraquat in the solutions used for spot spraying on tea plantations (0.3-0.4 g paraquat ion per litre), the high standard of personal hygiene exercised by the workers, and the low permeability of human skin to paraquat.     

Accumulation of chlorpyrifos on residential surfaces and toys accessible to children.

Quantitative examination of major pathways and routes of exposure to pesticides is essential for determining human risk. The current study was conducted in two apartments and examines the accumulation of the pesticide chlorpyrifos in childrens' toys after the time suggested for reentry after application. It has been established for the first time that a semivolatile pesticide will accumulate on and in toys and other sorbant surfaces in a home via a two-phase physical process that continues for at least 2 weeks postapplication. A summation of the above for a 3-6-year-old child yielded an estimated nondietary total dose of 208 microg/kg/day. Potential exposure from the inhalation pathway was negligible, while dermal and nondietary oral doses from playing with toys contributed to 39 and 61% of the total dose, respectively. If children with high frequency mouthing behavior are considered as candidates for acute exposure to chlorpyrifos residues, the estimated acute dose could be as high as 356 microg/kg/day. Routine reapplication of pesticides could lead to continued accumulation in toys and other sorbant surfaces, e.g., pillows, with large sorbant reservoirs, which can become a long-term source of exposure to a child. Estimates of a child's nondietary exposure to chlorpyrifos associated with toys and other sorbant surfaces for a period of 1 week following application appear to be of public health concern, and studies of actual childhood exposure from this pathway are warranted in the home environment. The above information should be used to determine if current procedures for postapplication reentry are sufficient and to evaluate the need for procedures to store frequently used household toys, pillows, and other sorbant objects during insecticidal application.     

Pigment epithelium–derived factor down regulates hyperglycemia-induced apoptosis via PI3K/Akt activation in goat retinal pericytes

Pigment epithelium–derived factor (PEDF) is a well-known protease inhibitor for angiogenesis in the eye, suggesting that loss of PEDF in eye is implicated in the pathogenesis of proliferative diabetic retinopathy. Since the role of PEDF in diabetic retinopathy is unclear, the effect of PEDF on different types of cells constituting the blood vessel has to be checked. Here, we have investigated the effects of PEDF under hyperglycemic conditions in retinal pericytes, isolated from goat’s eye and used to analyze the signaling pathway involved. High glucose increased the apoptotic cell death and intracellular reactive oxygen species generation, which was blocked on the addition of PEDF. PEDF was found to inhibit the apoptotic cell death and protect the cells via activating the PI3K/Akt pathway, which was analyzed with dominant negative Akt and constitutively active Akt–transfected cells. These results demonstrate that PEDF protects pericytes against the high glucose–induced apoptosis and dysfunction.     

Lutein attenuates oxidative stress markers and ameliorates glucose homeostasis through polyol pathway in heart and kidney of STZ-induced hyperglycemic rat model

Purpose

Lutein’s role on chronic hyperglycemia-induced oxidative stress and associated glucose homeostasis in heart and kidney is limited. Purpose of the study is to investigate the effect of lutein on cardiac and renal polyol pathway enzymes and oxidative stress markers under hyperglycemia-induced oxidative stress condition using streptozotocin (STZ)-injected rat model.

Methods

STZ-induced hyperglycemic (fasting blood glucose ≥11 mM) male Wistar rats were divided into two groups (n = 11/group). Group 1 received micellar lutein (39 nmol/day/rat) and group 2 (negative control) received micelle without lutein for 8 weeks. A separate group (no STZ injected) served as a positive control (n = 11/group). Oral glucose tolerance test (OGTT), biweekly urine glucose and activities of aldose reductase (AR) and sorbitol dehydrogenase (SDH) enzymes were assessed. Activities of antioxidant enzymes and antioxidant level were also evaluated.

Results

Lutein-administered hyperglycemic rats showed better glucose tolerance as evidenced with OGTT and biweekly urine glucose when compared to negative control. Activities of AR and SDH were decreased in heart and kidney of lutein-fed hyperglycemic rats. Also, they had significantly (p < 0.05) decreased malondialdehyde levels (66, 34, and 33 %) and increased reduced glutathione level (81, 18 and 92 %) in serum, heart and kidney, respectively. Altered antioxidant enzyme activities such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione transferase were also affected in serum, heart and kidney of lutein-fed diabetic group.

Conclusion

Lutein prevented cardiac and renal injury in STZ-induced hyperglycemic rats due to potential amelioration of altered activities in polyol pathway and oxidative stress markers.