Charged cyclodextrin-mediated sample stacking in micellar capillary electrophoresis. A simple method for enhancing the detection sensitivity of hydrophobic compounds.

The development of on-line sample stacking techniques for enhancing limits of detection of neutral analytes in micellar capillary electrophoresis (MCE) has recently gained much attention. Utilizing high-conductivity sample matrices to invoke sample stacking is promising, but requires the limited use of sample solubilizing agents such as alcohols in the sample matrix. In this study, we show how simple replacement of the sample solvent (methanol) with a solution of sulfated beta-cyclodextrin (s beta-CD) allows a significant increase in the sensitivity of detection of model hydrophobic analytes. This increase in sensitivity is accompanied by significant peak sharpening. Sulfated CDs in the sample matrix allow for effective solubilization of hydrophobic analytes without the use of organic solvents such as methanol. The testing of various sample matrix s beta-CD concentrations for their effect on peak sharpening identified 3 to 5% as optimal for the estrogen standards. The use of a s beta-CD sample matrix allowed for hydrostatic injections (3.5 kPa) of 297 s, compared with 4 s when the analytes were dissolved in methanol. A mechanism explaining the s beta-CD-induced effect involves an analyte transfer mechanism where the s beta-CDs, despite providing anodic mobility to analytes in the sample zone, are able to transfer analytes to trailing separation buffer micelles for "recycling" back into the sample zone without compromising the stacking process. The overall improvement in sensitivity allows detection of estrogens in the parts-per-billion range and stands to improve the utility of MCE as a bioanalytical technique.     

Dental implants. 8. Implant surgery to overcome anatomical difficulties

Autogenous grafts are considered to be the most predictable for replacement of deficient bones to facilitate implant treatment. Augmentation of soft tissue may also be required to improve aesthetics and function.     

Temporal lobe developmental malformations and hippocampal sclerosis: epilepsy surgical outcome

BACKGROUND: Temporal lobe developmental malformations coexist with mesial temporal sclerosis in the form of dual pathology with a high frequency of bilateral amygdala or hippocampal abnormalities. OBJECTIVE: The aim of this study was to correlate and compare the MRI findings and the surgical outcome in patients with temporal lobe developmental malformations (n = 20) and isolated mesial temporal sclerosis (n = 36). METHODS: MRI-based normalized volumetry of the amygdala and hippocampal formation in patients with unilateral temporal lobe developmental malformations and isolated mesial temporal sclerosis who underwent temporal lobe resections was performed. Seizure outcome was compared between groups at follow-up. RESULTS: The frequency of bilateral hippocampal or amygdala atrophy (p < 0.04) and combined hippocampal-amygdala atrophy (p < 0.02) was higher in patients with temporal lobe developmental malformations. Although no significant difference in postsurgical seizure-free status was found between the temporal lobe developmental malformations and isolated mesial temporal sclerosis groups (70% versus 91%), patients with temporal lobe developmental malformations and bilateral amygdala or hippocampal-amygdala atrophy had a significantly worse outcome (p < 0.02). CONCLUSION: Bilateral hippocampal atrophy is frequent in patients with temporal lobe developmental malformations. However, it is the presence of bilateral amygdala or amygdalo-hippocampal atrophy that is associated with a higher risk of seizure recurrence.     

Changes in iron histochemistry after hypoxic-ischemic brain injury in the neonatal rat

Iron can contribute to hypoxic-ischemic brain damage by catalyzing the formation of free radicals. The immature brain has high iron levels and limited antioxidant defenses. The objective of this study was to describe the early alterations in nonheme iron histochemistry following a hypoxic-ischemic (HI) insult to the brain of neonatal rats. We induced a HI insult to the right cerebral hemisphere in groups of 7-day-old rats. Rats were anesthetized, then their brains were perfused and fixed at 0, 1, 4, 8, 24 hr, and 1, 2, and 3 weeks of recovery. Forty-micron-thick frozen sections were stained for iron using the intensified Perls stain. Increased iron staining was first detected within the cytoplasm of cells with pyknotic nuclei at 4 hr of recovery. Staining increased rapidly over the first 24 hr in regions of ischemic injury. By 7 days recovery, reactive glia and cortical blood vessels also stained. Increased staining in gray matter persisted at 3 weeks of recovery, whereas white matter tracts had fewer iron-positive cells compared to normal. The early increase in iron staining could be caused by an accumulation of iron posthypoxicischemic injury or a change in iron from nonstainable heme iron to stainable nonheme iron. Regardless of the source, our results indicate that there is an increase in iron available to promote oxidant stress in the neonatal rat brain following hypoxia-ischemia.     

The emerging international policy agenda for reproductive health services in conflict settings

Over the past 20 years, shifts in the nature of conflict and the sheer numbers of civilians affected have given rise to increasing concern about providing appropriate health services in unstable settings. Concurrently, international health policy attention has focused on sexual and reproductive health issues and finding effective methods of addressing them. This article reviews the background to the promotion and development of reproductive health services for conflict-affected populations. It employs qualitative methods to analyse the development of policy at international level. First we examine the extent to which reproductive health is on the policy agendas of organisations active in humanitarian contexts. We then discuss why and how this has come about, and whether the issue has sufficient support to ensure effective implementation. Our findings demonstrate that reproductive health is clearly on the agenda for agencies working in these settings, as measured by a range of established criteria including the amount of new resources being attracted to this area and the number of meetings and publications devoted to this issue. There are, however, barriers to the full and effective implementation of reproductive health services. These barriers include the hesitation of some field-workers to prioritise reproductive health and the number and diversity of the organisations involved in implementation. The reasons for these barriers are discussed in order to highlight areas for action before effective reproductive health service provision to these populations can be ensured.     

Tyrosine kinase inhibitors. 15. 4-(Phenylamino)quinazoline and 4-(phenylamino)pyrido[d]pyrimidine acrylamides as irreversible inhibitors of the ATP binding site of the epidermal growth factor receptor.

A series of 6- and 7-acrylamide derivatives of the 4-(phenylamino)quinazoline and -pyridopyrimidine classes of epidermal growth factor receptor (EGFR) inhibitors were prepared from the corresponding amino compounds by reaction with either acryloyl chloride/base or acrylic acid/1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. All of the 6-acrylamides, but only the parent quinazoline 7-acrylamide, were irreversible inhibitors of the isolated enzyme, confirming that the former are better-positioned, when bound to the enzyme, to react with the critical cysteine-773. Quinazoline, pyrido[3,4-d]pyrimidine, and pyrido[3,2-d]pyrimidine 6-acrylamides were all irreversible inhibitors and showed similar high potencies in the enzyme assay (likely due to titration of the available enzyme). However the pyrido[3,2-d]pyrimidine analogues were 2-6-fold less potent than the others in a cellular autophosphorylation assay for EGFR in A431 cells. The quinazolines were generally less potent overall toward inhibition of heregulin-stimulated autophosphorylation of erbB2 (in MDA-MB-453-cells), whereas the pyridopyrimidines were equipotent. Selected compounds were evaluated in A431 epidermoid and H125 non-small-cell lung cancer human tumor xenografts. The compounds showed better activity when given orally than intraperitoneally. All showed significant tumor growth inhibition (stasis) over a dose range. The poor aqueous solubility of the compounds was a drawback, requiring formulation as fine particulate emulsions.     

Acute and chronic effects of ginseng total saponin and amphetamine on fixed-interval performance in rats

The effect of ginseng total saponin (GTS) on amphetamine (AMPH)-induced disruption of fixed-interval (FI) responding in rats was examined. GTS (50 mg/kg) significantly improved the temporal responding impaired by 2 mg/kg of AMPH. A higher dose of 100 mg/kg GTS disrupted performance when given alone; this disruption was reversed by a low dose of AMPH (0.5 mg/kg) and tolerance developed to the effects of GTS with its repeated administration. Neurochemical analysis revealed that GTS (50 mg/kg) attenuated the increase in striatal dopamine caused by AMPH leading to the conclusion that brain dopamine may partially mediate the behavioral effects of GTS.     

Risk factors for orofacial and limbtruncal tardive dyskinesia in older patients: a prospective longitudinal study

Although there is a consensus that orofacial and limbtruncal subtypes of tardive dyskinesia (TD) exist and may represent distinct pathophysiologic entities, few studies have examined the incidence of and risk factors associated with the development of these TD subtypes. Two hundred and sixty-six middle-aged and elderly outpatients with a median duration of 21 days of total lifetime neuroleptic exposure at study entry were evaluated at 1- to 3-month intervals. Using mild dyskinesia in any part of the body for diagnosis of TD, the cumulative incidence of orofacial TD was 38.5 and 65.7% after 1 and 2 years, respectively, whereas that of limbtruncal TD was 18.6 and 32.6% after 1 and 2 years. Preclinical dyskinesia was predictive of both orofacial and limbtruncal TD. History of alcohol abuse or dependence was a significant predictor of orofacial TD only whereas tremor was a significant predictor of limbtruncal TD only. Findings support suggestions that orofacial and limbtruncal TD may represent specific subsyndromes with different risk factors.