Biodistribution characteristics of mannosylated and fucosylated O/W emulsions in mice

Cell-specific drug delivery is one of the most promising strategies for improving therapeutic efficiency and minimizing systemic toxicity. Carrier systems devoted to receptor-mediated targeting need to be developed. In the case of liver-non-parenchymal cell-specific targeting systems, glycosylated emulsions have been developed as carriers for lipophilic drugs and/or peptides. This present study demonstrates the in vivo disposition behaviour and pharmacokinetic characteristics of mannosylated (Man-) and fucosylated (Fuc-) emulsions incorporated with cholesten-5-yloxy-N-(4-((1-imino-2-D-thiomannosylethyl)amino)alkyl)formamide (Man-C4-Chol) and its fucosylated derivatives (Fuc-C4-Chol), respectively. Man- (or Fuc-) emulsions are composed of soybean oil, EggPC and Man-C4-Chol (or Fuc-C4-Chol) in a weight ratio of 70:25:5. After intravenous administration to mice, these two types of [(3)H]cholesteryl hexadecyl ether (CHE)-labelled glycosylated emulsions were rapidly eliminated from the blood circulation and preferentially recovered in the liver. In contrast, bare (Bare-) emulsions composed of soybean oil:EggPC:cholesterol (Chol) in a weight ratio of 70:25:5 were more retained in the blood circulation. The hepatic uptake clearances of Man- and Fuc-emulsions were 3.3- and 4.0-times greater than that of Bare-emulsions. Interestingly, the hepatic uptake clearance of Fuc-emulsions was significantly higher that that of Man-emulsions. The uptake ratios by non-parenchymal cells (NPC) and parenchymal cells (PC) (NPC/PC ratio) for Bare-, Man- and Fuc-emulsions were found to be 0.4, 2.0 and 2.9, respectively. The hepatic uptakes of [(3)H]CHE-labelled Man- and Fuc-emulsions were reduced by pre-dosing with glycosylated proteins and liposomes. These results clearly support the conclusion that Man- and Fuc-emulsions are promising carrier systems for liver NPC-specific targeting via receptor-mediated mechanism.     

The economic consequences for parents of losing an adult child to AIDS: evidence from Thailand

An examination of the economic consequences for older-age parents of losing an adult child to AIDS in Thailand based on quantitative data derived from a key informant study and a direct interview survey with parents yielded the following main findings: (1) parents frequently paid for their children's care and treatment, but government health insurance and to a lesser extent welfare measures helped alleviate these expenses; (2) parental caregiving often disrupted economic activity, although the resulting opportunity costs were limited by the typically short duration of caregiving; (3) parents commonly paid for funeral costs but benefited from funeral society memberships and customary contributions from those attending; (4) only a minority of parents supported AIDS orphans although orphaned grandchildren often ended up with their grandparents; (5) most deceased children had contributed financially to the parental household but only a minority were main providers. Poorer parents, however, were most likely to lose a main provider and experience severe financial hardship; and (6) although poorer parents spent much less on expenses related to the illness and death of their children, they were much more likely than better-off parents to be seriously burdened by these expenses. Programs are needed to address the plight of AIDS parents but should target those who are most susceptible to resulting economic hardship.     

Oxidized alpha-1 antitrypsin as a predictive risk marker of opisthorchiasis-associated cholangiocarcinoma

The oxidized alpha-1 antitrypsin (ox-A1AT) is one modified form of A1AT, generated via oxidation at its active site by free radicals released from inflammatory cells which subsequently are unable to inhibit protease enzymes. The presence of ox-A1AT in human serum has been used as oxidative stress indicator in many diseases. As oxidative/nitrative damage is one major contributor in opisthorchiasis-driven cholangiocarcinogenesis, we determined A1AT and ox-A1AT expression in human cholangiocarcinoma (CCA) tissue using immunohistochemical staining and measured serum ox-A1AT levels by ELISA. A1AT and ox-A1AT were found to be expressed in the tumor of CCA patients. The group with high expression has a significant poor prognosis. Serum levels of ox-A1AT were also significantly higher in groups of patients with heavy Opisthorchis viverrini infection, advanced periductal fibrosis (APF) and CCA when compared with healthy controls (P?<?0.001). Odds ratio (OR) analysis implicated high ox-A1AT levels as a risk predictor for APF and CCA (P?<?0.001; OR?=?140.5 and 22.0, respectively). In conclusion, as APF may lead to hepatobiliary diseases and an increased risk of CCA development, our results identified ox-A1AT as a potential risk indicator for opisthorchiasis-associated CCA. This marker could now be explored for screening of subjects living in endemic areas where the prevalence of opisthorchiasis still remains high.     

Thyroid hormone increases mRNA and protein expression of Na+-K+-ATPase alpha2 and beta1 subunits in human skeletal muscles

CONTEXT: Thyroid hormone regulates specific Na+-K+-ATPase isoforms in rodent skeletal muscles. No study has examined this relationship in human tissues. OBJECTIVE: This study investigated the effect of hyperthyroid status on the expression of the alpha- and beta-subunits of the Na+-K+-ATPase. DESIGN: The vastus lateralis muscles from eight hyperthyroid patients were biopsied before and after treatment. Ten age-matched euthyroid subjects served as controls. RESULTS: In hyperthyroid patients, the average T3 level was three times higher in pretreatment compared with posttreatment (262 +/- 75 vs. 86 +/- 21 ng/dl, P = 0.001). The relative mRNA expression of the alpha2, but not alpha1 or alpha3, subunit was increased approximately 3-fold in pretreatment (2.98 +/- 0.52 vs. 0.95 +/- 0.40, P < 0.01), whereas that of beta1, not beta2 or beta3, subunit was increased approximately 2.8-fold in pretreatment (2.83 +/- 0.38 vs. 1.10 +/- 0.27, P < 0.01). The relative mRNA expression of the alpha2 and beta1 subunits was positively correlated with the serum T3 (r = 0.75, P = 0.001 and r = 0.66, P = 0.003, respectively). Immunohistochemistry studies revealed an increase in protein abundance of the alpha2 and beta1, but not alpha1 or beta2, subunits in the plasma membrane of muscle fibers of hyperthyroid patients, which decreased after treatment. CONCLUSIONS: This provides the first evidence that, in human skeletal muscles, thyroid hormone up-regulates the Na+-K+-ATPase protein expression at least, in part, at mRNA level, and the alpha2 and beta1 subunits play the important role in this regulation.     

HIV/AIDS-related knowledge and attitudes: a comparison of older persons and young adults in Thailand.

Levels of AIDS related knowledge are widely assumed to be high in Thailand, a country with probably the most effective response to the HIV/AIDS pandemic to date in the developing world. But efforts to verify these levels are sparse in recent years, and very little attention has ever been paid to AIDS knowledge and attitudes within the Thai older population. Because many Thai older persons (aged 50 and over) remain sexually active late in life, and because many more will be involved in interactions with and care taking of young adult persons suffering from AIDS, we explore AIDS knowledge and attitudinal data we collected during 1999 from a sample of 773 older Thais from four provinces and Bangkok. The sample provinces were chosen to include a wide range of prevalence levels and social contexts regarding the epidemic. We compare the results with data from a sample of 398 young adults using the same questionnaire, collected at the same sites, at the same time (total N = 1,171). We find an overall high level of awareness about AIDS across our age groups of interest, but also identify important deficiencies among the young adults and especially among the older Thais. Implications of the findings are discussed.     

Novel sorbents for removal of gadolinium-based contrast agents in sorbent dialysis and hemoperfusion: preventive approaches to nephrogenic systemic fibrosis

Many forms of organocomplexed gadolinium (Gd) contrast agents have recently been linked to a debilitating and a potentially fatal skin disease called nephrogenic systemic fibrosis (NSF) in patients with renal failure. Free Gd released from these complexes via transmetallation is believed to be the most important trigger for NSF. In this work, nanostructure silica materials that have been functionalized with 1-hydroxy-2-pyridinone (1,2-HOPO-SAMMS) have been evaluated for selective and effective removal of both free and chelated Gd (gadopentetate dimeglumine and gadodiamide) from dialysate and blood. 1,2-HOPO SAMMS has high affinity, rapid removal rate, and large sorption capacity for both free and chelated Gd, properties that are far superior to those of activated carbon and zirconium phosphate currently used in the state-of-the-art sorbent dialysis and hemoperfusion systems. The SAMMS-based sorbent dialysis and hemoperfusion will potentially provide an effective and predicable strategy for removing the Gd from patients with impaired renal function after Gd exposure, thus allowing for the continued use of Gd-based contrast magnetic resonance imaging while removing the risk of NSF.From the Clinical EditorChelated gadolinium (Gd) contrast agents have been linked to a debilitating disease called nephrogenic systemic fibrosis (NSF) in patients with renal failure. Free Gd+³ released from the contrast agents is believed to be the trigger for NSF. In this work, functionalized nanostructured silica materials were evaluated for removal of both free and chelated gadolinium both from dialysate and blood. The new method demonstrated a rapid removal rate and large sorption capacity, and overall was far superior to currently used state-of-the-art sorbent dialysis and hemoperfusion systems.     

Designing Dendrimers for Drug Delivery and Imaging: Pharmacokinetic Considerations

Dendrimers have well-organized high branches with a layered architecture providing a series of versatile chemical modification for various purposes. Consequently, this dendrimer nanotechnology explores a new promising class of nanoscale carriers for therapeutic drugs and imaging reagents using passive and active targeting approaches. By controlling dendritic structures, the biological fate of dendrimer/dendrimer-based drugs can be significantly altered based on their intrinsic physicochemical properties, including the hydrophilicity of the unit molecules, particle size, surface charge, and modification. Accordingly, pharmacokinetic aspects play an important role in the design and development of dendrimer systems for successful in vivo application and clinical translation. This review focuses on the recent progress regarding dendritic architectures, structure-related toxicity, and critical factors affecting the pharmacokinetics and biodistribution of dendrimer/dendrimer-based drugs. A better understanding of the basic aspects of dendritic systems and their pharmacokinetics will help to develop a rationale for the design of dendrimers for the controlled delivery of drugs and imaging reagents for therapeutic or diagnostic purposes.     

Self-esteem and student nurses: a cross-cultural study of nursing students in Thailand and the UK

Abstract Self-esteem is a key feature in a person's perception of their own worth. This report is of a study of the reported self-esteem levels of two groups of student nurses: one in Thailand and one in the UK. Purposive samples of 120 Thai students and 101 UK undergraduate nursing students were given the Culture-Free Self-Esteem Inventory (CFSEI-2). The CFSEI-2 is a self-reported inventory, which measures an individual's perception of self. The findings of the study indicate that the perceptions of own self-esteem in undergraduate student nurses in the UK and in Thailand were comparable to the normal ranges of self-esteem as assessed by the instrument. An independent sample t -test revealed that there were no significant differences in mean overall and subscale self-esteem scores between UK and Thai nursing students. There were no indications of differences in levels of self-esteem for UK and Thai nursing students experiencing different parts of their training.