Fate of micelles and quantum dots in cells.

Micelles and quantum dots have been used as experimental drug delivery systems and imaging tools both in vitro and in vivo. Investigations of their fate at the subcellular level require different surface-core modifications. Among the most common modifications are those with fluorescent probes, dense-core metals or radionucleids. Cellular fate of several fluorescent probes incorporated into poly(caprolactone)-b-copolymer micelles (PCL-b-PEO) was followed by confocal microscopy, and colloidal gold incorporated in poly 4-vinyl pyridine-PEO micelles were developed to explore micelle fate by electron microscopy. More recently, we have examined quantum dots (QDs) as the next-generation-labels for cells and nanoparticulate drug carriers amenable both to confocal and electron microscopic analyses. Effects of QDs at the cellular and subcellular levels and their integrity were studied. Results from different studies suggest that size, charge and surface manipulations of QDs may play a role in their subcellular distribution. Examples of pharmacological agents incorporated into block copolymer micelles, administered or attached to QD surfaces show how the final biological outcome (e.g. cell death, proliferation or differentiation) depends on physical properties of these nanoparticles.     

Sonographic evaluation of gallbladder kinetics: in vitro and in vivo comparison of different methods to assess gallbladder emptying.

In an in vitro study, 10 gallbladders of adult pigs and 6 gallbladders of lambs, all removed immediately after slaughtering, were stimulated in a water bath by electric means to induce active contraction. Gallbladder emptying was followed by ultrasonography employing five measurement procedures: (1) gallbladder width, (2) longitudinal planimetry, (3) transverse planimetry, (4) ellipsoid method, and (5) sum of cylinders method. In an in vivo investigation, gallbladder emptying of 30 volunteers (12 healthy subjects, 18 diabetics) was evaluated in the same way after ingestion of a fatty meal. Gallbladder width was found to be unsuitable to estimate the decrease in gallbladder volume due to a nonlinear relation of the parameters. Longitudinal planimetry tended to be less valid than transverse planimetry in assessing gallbladder volume reduction. The most valid estimation of gallbladder volume decreases was obtained by the two three-dimensional procedures. However, in neither in vitro nor in vivo could a significant difference between the sum of cylinders method and the ellipsoid method in determining relative volume reduction be established. We conclude that a three-dimensional measurement procedure should be used for valid assessments of gallbladder motility. However, according to our data there is no advantage in using the time-consuming sum of cylinders method compared to the simple ellipsoid method.     

Complications of orthodontic-orthognathic surgery treatment in mentally handicapped patients.

AIM: The aim of this study was to analyse possible intra- and postoperative complications and long-term results in combined orthodontic-orthognathic treatment of mentally handicapped patients compared with a control group of patients without handicap. PATIENTS AND METHODS: A group of 20 mentally handicapped patients (male = 7, female = 13) and of 102 non-handicapped patients (male = 36, female = 66) were evaluated retrospectively. The results of the two point-discrimination sensory test and the cephalometric findings of both groups were assessed. Complications during and after the operation, the results of nerve function tests and relapse rates were reported. The statistical analysis was carried out using binary logistical regression analysis with adjustment according to the diagnosis and the type of operation (p < 0.05) RESULTS: No significant differences could be found between the mentally handicapped and the non-handicapped patients. Only the nerve function test immediately postoperatively revealed differences between the two patient groups. The relapse rate in mentally handicapped patients was similar to non-handicapped patients. Forty-seven months after the operation, relapse (change in the ANB angle of more than 0.5 degrees ) was observed in four patients only (handicapped patients). CONCLUSION: Orthognathic surgical procedures in mentally handicapped patients can be carried out with a similarly high success rate as in mentally healthy patients.     

Challenges and opportunities of nursing care in special-needs shelters.

Hurricanes Katrina and Rita forced many individuals along the coast of Texas and Louisiana to seek shelter inland. Among the evacuees were residents with special needs and residents of nursing homes and group homes caring for mentally retarded and physically disabled persons. Many nurses volunteered to provide health care for those in need. This article discusses challenges and opportunities that were encountered by nurses volunteering in special-needs shelters. Issues related to human and physical resources, patient care, and confidentiality are discussed including lessons learned. As nurses who cared for evacuees in the shelter, it is hoped some of the lessons learned can be utilized in future disasters.     

In VivoStudies of Adenovirus-Based p53 Gene Therapy for Ovarian Cancer

Objectives.To test the safety, efficacy, and toxicity of gene therapy using wild-type p53-expressing adenovirus (Ad-CMV-p53) in a nude mouse model with intraperitoneal (ip) 2774 human ovarian cancer cell line that contains a p53 mutation.Study design.An initial study of adenovirus tolerance was determined in nude mice by a single ip injection of increasing doses of Ad-CMV-p53. Nude mice were implanted with an LD₁₀₀dose of 1 × 10⁷cells. To study the efficacy and specificity of Ad-CMV-p53 treatment, the mice received treatment with different adenovirus constructs. One group received Ad-CMV-p53 and another group received a control adenovirus construct, Ad-CMV-βgal. To study the treatment response to Ad-CMV-p53, the mice were divided into groups and received various treatment schedules of 1 × 10⁸pfu of Ad-CMV-p53.Results.The mice tolerated Ad-CMV-p53 without adverse effects at doses of 1 × 10⁸pfu. The response to Ad-CMV-p53 showed significant survival duration in each dose regimen, with a survival time greater than that of untreated animals (P= 0.0173). However, no statistically significant survival advantage was observed between Ad-CMV-p53- and Ad-CMV-βgal-treated mice.Conclusions.These studies show that at the adenovirus dose and administration regimen used, there is effective but not specific 2774 tumor growth inhibitionin vivo.Efficient introduction of biologically active genes into tumor cells would greatly facilitate cancer therapy. Thus, although promising, these results caution that much effort will be required to realize the potential for clinical application of adenovirus-based ovarian cancer gene therapy.     

Interaction between thiol-modifying agents and P1075, a KATP channel opener, in rat isolated aorta

In vascular smooth muscle, openers of ATP-dependent potassium channels (K _ATP channels), such as P1075 (N-cyano-N’-(1,1-dimethylpropyl)-N’’-3-pyridylguanidine), produce relaxation. In this study we have investigated the effects of thiol-modifying agents on the binding of P1075 and on the ⁸⁶Rb⁺ efflux stimulating and vasorelaxant effects of the opener in rat aortic rings. The increase in ⁸⁶Rb⁺ efflux induced by P1075 was taken as a qualitative measure of K⁺ channel opening. The hydrophilic SH-group-oxidizing substance, thimerosal (1 to 100μM), abolished specific binding of [³H]-P1075 with an IC₅₀ value of 7.6±1.2μM; at 30μM, the half time for inhibition was 38min. Two other thiol-oxidizing agents, PMB (4-hydroxy-mercuribenzoic acid) and DTBNP (2,2’-dithio-bis(5-nitropyridine)), inhibited binding up to 86% and 44%, respectively. The disulphide bond reducing substance, DTT (1,4-dithiothreitol, 0.1 to 1mM), reduced [³H]-P1075 binding by up to 20% and partially reversed the inhibitory effect of thimerosal. In ⁸⁶Rb⁺ efflux experiments, thimerosal (3 to 100μM) concentration-dependently increased basal efflux but inhibited P1075-stimulated tracer efflux with an IC₅₀ value of 7±1μM. The inhibitory effect occurred with a half-time of approximately 8min and was essentially reversed by DTT. In rings precontracted with noradrenaline, thimerosal inhibited the vasorelaxant effect in a noncompetitive manner, shifting the concentration-relaxation curves to the right and reducing maximum relaxation.The data show that oxidation of thiol groups interferes with the binding of the K _ATP channel opener, P1075; concomitantly, the ⁸⁶Rb⁺ efflux stimulating and the vasorelaxant effects are inhibited. Reduction of disulphide bonds by DTT has only minor effects on the action of P1075. Collectively, the results suggest that intact thiol groups are essential for the functioning of the K_ATP channel in rat aorta. The different kinetics governing the inhibition of opener binding and of opener-stimulated ⁸⁶Rb⁺ efflux suggest that the SH-groups involved in the two processes differ in their accessibility to thimerosal and/or in their reactivity. Received: 7 April / Accepted: 9 July 1997     

Advances in the treatment of depression in older adults

Depressive symptoms in older adults are common, but the minority of elderly meet criteria for major depressive disorder. This has led to confusion regarding the recognition of diagnosis, approach to treatment, and monitoring of outcomes in this needy population. Few depressed older adults are willing to seek treatment from psychiatrists or mental health specialists. Treatment approaches to the depressive spectrum of disorders in late life, which encompasses major and minor depressive disorder, dysthymic disorder, and mood disorders related to medical conditions, must include evidence-based algorithms that can be delivered in a variety of health care settings. Several recent multisite trials have advanced the use of collaborative care models and the systematic stepwise approach to the treatment of depression and anxiety states in older adults. This offers the ability to provide effective treatment of depression for older adults, consistent with current guidelines, in primary care and specialized health care settings.     

Sham in CAM

Several unique methodological challenges exist concerning the choice of the most appropriate comparator or control group for clinical research in complementary and alternative medicine (CAM). This article reviews the four major types of control groups (active control, placebo or sham, no intervention control, and different protocols of the experimental intervention), noting the different questions they answer and the different contexts in which they may be used, and discusses how this framework may be applied to CAM research in an effort to avoid methodologically flawed study designs. The choice of comparator depends on complex factors such as the research question being asked, the most plausible competing rival hypotheses, and logistical considerations related to ethics, methodology and feasibility. For example, for sham to be an effective comparator it must capture the ‘nonspecific’ elements of the treatment without containing those that are ‘specific’ to the research question at hand. However, as demonstrated by the examples of acupuncture and energy medicine, designing such sham intervention is not always easy. Controlling for social interaction between practitioners and subjects, addressing issues around ethics, having good-quality measurement of treatment integrity and intensity, and selecting practitioners of sufficient competence when doing a sham process are other important parts of correct design choices. In the light of these complexities, clinicians and researchers alike need a better match between the research questions and the design employed in order for their research to be both scientifically valid and clinically meaningful.     

Apoptosis: understanding the new molecular pathway.

Advances in science have increased the knowledge of how cells die in the body (apoptosis). A basic understanding of this process can improve nurses' ability to review new scientific literature and enable them to provide safer bedside care.