Adjuvanticity of stealth liposomes on the immunogenicity of synthetic gp41 epitope of HIV-1

Present study aims to enhance the efficacy of liposomes as an adjuvant by steric protection and strengthen the path of vaccine research. PEG grafted liposomes carrying epitopes on their surface showed enhanced adjuvanticity than liposomes carrying epitopes for elicitation and prolongation of immune response to an antigenic epitope of gp41, a transmembrane protein of HIV-1. The multiples of epitope were incorporated onto the surface of liposomes by conjugating them with phosphatidylethanolamine that was used in the formulation of liposomes at an optimized ratio. Furthermore, the liposomes carrying epitopes on their surface were sterically protected by shielding with methoxy-poly(ethylene glycol), mass 20 kDa. Methoxy-poly(ethylene glycol) was activated to its electrophilic N-succinimide carbonate derivative, methoxy-poly(ethylene glycol)-N-succinimide carbonate, that formed a urethane linkage with the amino group of phosphatidylethanolamine. The epitope was covalently coupled to phosphatidylethanolamine through an amide bond between the -COOH group of the epitope and -NH2 group of phosphatidylethanolamine under the catalysis of 1-ethyl-3-(3-dimethylaminopropy-1)-carbodiimide. PEG grafted epitopes carrying liposomes showed about two times higher immune response and prolonged persistence of antibodies than that of liposomes carrying epitopes without PEG moieties.     

Recurrent bullous retinal detachments from photodynamic therapy for idiopathic polypoidal choroidal vasculopathy

PURPOSE: To report the recurrent bullous retinal detachments as complications of photodynamic therapy (PDT) for idiopathic polypoidal choroidal vasculopathy (IPCV). DESIGN: Interventional case report. METHODS: A pseudophakic 84-year-old-woman had IPCV and decreased vision. Angiography demonstrated macular leakage. PDT with verteporfin was applied. Two days later, visual acuity decreased from 20/50 to 20/400. Examination revealed extensive inferior subretinal fluid, which mimicked a pseudophakic rhegmatogenous retinal detachment. A scleral buckle was placed; no retinal breaks were identified. RESULTS: Vision and fluid resolved over three weeks. Four months later, examination revealed decreased vision and persistent leakage. Two days after repeat PDT, bullous exudative macular detachment recurred. Detachment resolved over two weeks; visual acuity returned to 20/50. CONCLUSION: IPCV that is treated with PDT may be complicated by iatrogenic bullous exudative retinal detachments that resemble rhegmatogenous detachments. Modified treatment parameters may reduce the risk of recurrence. The natural history likely includes spontaneous resolution and visual recovery.     

Superantigen-primed T cells exposed to 2,3,7,8–tetrachlorodibenzo-p-dioxin (TCDD) replicate poorly following recall encounter

The current study investigated the effect of tetrachlorodibenzo-p-dioxin (TCDD) on the ability of staphylococcal enterotoxin A (SEA)-primed T cells to divide by dual-labeling the cells with 5,6–carboxyfluorescein diacetate succinimidyl ester (CFSE) and antibodies against the specific T cell receptors. C57BL/6 wild-type mice were injected ip with TCDD (10 μg/kg body weight) followed by hind footpad injections of SEA (10 μg/footpad). The draining popliteal lymph nodes (PLN) were harvested 1–4 days posttreatment, labeled with CFSE and cultured for 1–4 days without further stimulation or in the presence of the recall antigen. TCDD-exposed SEA-reactive Vβ3+ and Vβ11+ T cells showed decreased cell divisions upon in vitro culture in the absence of any stimulation, which correlated with increased levels of apoptosis. The recall cell-division response was also defective in SEA-reactive T cells isolated from TCDD-exposed mice. However, during the recall response, cells from TCDD-exposed mice did not exhibit a defect in apoptosis, suggesting the defective recall response may result from a state of anergy rather than increased apoptosis. Using AhR knockout (KO) mice, we found AhR involvement in the regulation of defective cell division and apoptosis induced by TCDD. Together, these data demonstrate, while TCDD-induced apoptosis may account for the decreased primary T cell proliferative response, that the reduced cell division seen during subsequent exposure to recall antigen may result from a state of anergy. The study also demonstrates that a combined use of superantigen and CFSE may offer a simple and useful tool to monitor the ability of immunotoxicants to alter the proliferative responsiveness of antigen-specific T cells.     

Phytochemical composition of essential oil from seeds of Zingiber roseum Rosc. and its antispasmodic activity in rat duodenum

A combination of GC and GC-MS revealed the presence of 60 compounds out of which 47 compounds (96.2% of the oil) were identified in the essential oil of seeds of Zingiber roseum Rosc., the major compounds being alpha-pinene, beta-pinene, limonene, p-cymene, alpha-terpineol and verticiole. The unique feature is the dominant presence of mono- and sesquiterpene hydrocarbons which make about 82% of the oil. The oil showed myorelaxant activity on isolated rat duodenal smooth muscle. The Zingiber roseum seed essential oil (ZRSEO) relaxed both cabachol- and KCl-induced contractile responses with IC(50) of non-significant difference. The results confirm a common mechanism in both the types of action of ZRSEO and suggests a probable inhibitory effect of ZRSEO on influx of Ca(2+) through cell membrane of rat duodenal smooth muscle.     

Failure of standard antimicrobial therapy in children aged 3-59 months with mild or asymptomatic HIV infection and severe pneumonia

OBJECTIVE: To determine whether children aged 3-59 months with mild or non-symptomatic human immunodeficiency virus (HIV) infection and WHO-defined severe pneumonia have a higher failure rate than do HIV-uninfected children when treated with the standard WHO treatment of parenteral penicillin or oral amoxicillin. METHODS: This study was a planned sub-analysis of a randomized trial of 3-59-month-old children presenting with WHO-defined severe pneumonia (the APPIS study). We included two sites with high HIV prevalence in Durban, South Africa and Ndola, Zambia. Primary outcome measures were clinical treatment failure at day 2 and day 14. CLINICALTRIALS.GOV IDENTIFIER: CT00227331http://www.clinicaltrialsgov/show/NCT00227331). FINDINGS: Of the 523 children enrolled, HIV status was known for 464 participants; 106 (23%) of these were infected with HIV. By day 2, 57 (12.3%) children had failed treatment and 110 (23.7%) failed by day 14. Twenty (18.9%) HIV-infected children failed by day 2 compared with 37 (10.3%) uninfected children (adjusted odds ratio (OR) 2.07; 95% confidence interval (CI): 1.07-4.00). Thirty-four (32.1%) HIV-infected children failed treatment by day 14 compared with 76 (21.2%) uninfected children (adjusted OR 1.88; 95% CI: 1.11-3.17). Analysis stratified by age showed that the greatest differential in treatment failure at day 2 and day 14 occurred in the children aged 3-5 months. CONCLUSIONS: HIV-infected children with severe pneumonia fail WHO-standard treatment with parenteral penicillin or amoxicillin at day 2 and day 14 more often than do HIV-uninfected children, especially young infants. Standard case management of acute respiratory infection (ARI) using WHO treatment guidelines is inadequate in areas of high HIV prevalence and reappraisal of empiric antimicrobial therapy is urgently needed for severe pneumonia associated with HIV-1.