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Development of emulsion type new vehicle for soft gelatin capsule. I. Selection of surfactants for development of new vehicle and its physicochemical properties.

Screening of surfactants was carried out to develop an oil in water (o/w) emulsion type new vehicle for a soft gelatin capsule (SGC), using polyethyleneglycol 400 (PEG 400) as hydrophilic phase and medium chain triglyceride (Miglyol 810), propyleneglycol dicaprylate (Sefsol 228) or soybean oil as hydrophobic phase (PEG 400: hydrophobic phase: surfactant = 87:10:3) and by means of simple homogenization. Polyoxyethylene (20) cetylether (BC-20TX), which can form homogeneous and viscous white gels using the above hydrophilic and hydrophobic phase combination, was selected as a model surfactant for developing the new vehicle. Using Miglyol 810 as hydrophobic phase, a model new vehicle formulation (PEG 400:water:Miglyol 810: BC-20TX = 77:10:10:3) was prepared, and its physicochemical properties were evaluated. The particle size distribution of the new vehicle, after diluting about 3000 times with water, ranged from about 0.5 to 50 microns. Furthermore, the new vehicle had thixotropic property at room temperature (about 25 degrees C) and temperature-dependent gel-sol transforming property with the transformation temperature of about 37 degrees C. These properties meet the requirement for encapsulation of the new vehicle in SGC and suggest that it can be expected to form the o/w emulsion state in the aqueous environment in the stomach. The rheological properties would also make it advantageous for use in other dosage forms such as suppository, cataplasm or liniment.

Capsules↗

Development to the blastocyst stage of pig embryos cultured in the amniotic fluid of developing chick embryos.

Early-stage pig embryos were collected from superovulated donor gilts (60-72 hr post hCG injection) and co-cultured in modified Brinster medium for ovum culture (mBMOC-2) + porcine oviduct epithelial cells (POEC) or in the amniotic fluid of a developing chick embryo (CEAm). The development rate to the compacted morulae or blastocyst stage was significantly higher (P < 0.01) in embryos co-cultured in CEAm (60.0%) than those co-cultured in mBMOC-2 + POEC (18.0%). The results indicate that CEAm could be used for production of compacted morulae or blastocysts from early-stage pig embryos. This culture system could also be valuable in situations where a CO2 controlled incubator is not available.

Amniotic Fluid↗

Functional development of oligodendrocytes and open-field behavior in developing rats: an approach using monoclonal antibody to immature oligodendrocytes.

To examine the relation between functional development of oligodendrocytes and open-field behavior during the postnatal period, a mouse monoclonal antibody termed 14F7, which predominantly labels stage-specific immature oligodendrocytes, was employed. Antibody 14F7 was administered intraperitoneally into male pups on day 3 and 4 after birth. The open-field test was performed on days 12 and 18 of the postnatal period. Horizontal activity increased remarkably with the growth of pups. On day 18, horizontal activity in the group with 14F7 was significantly higher than the control, while there was no significant difference between treatments on day 12. In contrast to the horizontal activity, the frequency of hind leg rearing, vertical activity, in the group with 14F7 was significantly lower than that in the control. On day 12, choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities in the cerebral cortex were similar between the groups. These activities increased with the growth of pups in both groups. In the 14F7 group on day 18, ChAT activity was the same as the control, whereas AChE activity was significantly lower compared with the control. These results suggest that neonatal exposure to 14F7 induces abnormal neurotransmission by reducing the degradation of acetylcholine and alters the spontaneous activities in developing rats.

Acetylcholinesterase↗

Diagnosis of MDR-TB: a developing world problem on a developed world budget.

The resurgence of tuberculosis worldwide has been accompanied by an increase in the incidence of multidrug-resistant tuberculosis on all continents. While significant advances have been made in the rapid and accurate diagnosis of Mycobacterium tuberculosis, the molecular biology methods used in the research laboratory to elucidate the mechanisms of drug resistance cannot be transferred to the centers delivering patient care. These methods require skilled operators, cumbersome protocols and extravagant expense. A number of companies that already have a large investment in M. tuberculosis diagnostics are adapting their high-throughput technology to drug susceptibility testing. These methodologies are not applicable to the developing world not only because of the costs involved but through a lack of infrastructure that is required to operate these machines and deliver specimens to the point of testing. Alternative technologies for drug susceptibility testing that do not rely on an investment in expensive hardware are presented and their potential use in the field is discussed. Though still relatively expensive to perform, these newer innovations may lead to the development of less intricate technologies that have universal application and begin to move away from our obsession with molecular-based diagnostics to produce on all encompassing gold standard.

Drug Resistance, Multiple, Bacterial↗

Use of monoclonal antibodies developed against chicken coccidia (Eimeria) to study invasion and development of Eimeria reichenowi in Florida sandhill cranes (Grus canadensis).

Eimeria gruis and Eimeria reichenowi are common coccidial parasites of a number of species of cranes. Until recently, little was known about either the site for invasion or the dynamics of early development of the crane coccidia because of the difficulty of identifying sporozoites and early developmental stages of these parasites by conventional staining methods. In the present study, monoclonal antibodies (MAbs) elicited against Eimeria spp. of chickens and turkeys were found to cross-react with sporozoites and developmental stages of E. reichenowi in the tissues of Florida sandhill cranes (Grus canadensis). With these Mabs, E. reichenowi sporozoites were found in specimens taken at 6 hr postinoculation (PI) from just proximal to Meckel's diverticulum in the jejunum to the ileocecal juncture. Fewer were found in the ceca and rectum and none in the duodenal loop. At 24 hr PI, there were markedly fewer sporozoites and their location had shifted to the duodenum. No stages were seen in intestinal cells at 5 days PI (DPI), but trophozoites had developed in the liver and spleen. At 10 DPI, sexual stages were detected in the intestine from the duodenal loop through Meckel's diverticulum but not in other organs. By 14 DPI, numerous developmental stages were detected in the intestine (ceca and jejunum), liver, and lungs but not in the heart, kidney, or brain. The number, location, and maturity of the stages in the ceca differed markedly from those in the jejunum.

Animals↗

Developments in antiviral drug design, discovery and development in 2004.

This article summarizes key aspects of progress made during 2004 toward the design, discovery and development of antiviral agents for clinical use. Important developments in the identification, characterization and clinical utility of inhibitors of human immunodeficiency virus; the hepatitis viruses, hepatitis B, hepatitis C; the herpes family of viruses, herpes simplex viruses 1 and 2, varicella zoster virus, Epstein-Barr virus and human cytomegalovirus; the respiratory viruses, influenza, respiratory syncytial virus, human metapneumovirus, picornaviruses, measles and the severe acute respiratory syndrome coronavirus; human papilloma virus; rotavirus; Ebola virus and West Nile virus, are reviewed.

Amino Acid Sequence↗

Conserved functions of Ikaros in vertebrate lymphocyte development: genetic evidence for distinct larval and adult phases of T cell development and two lineages of B cells in zebrafish.

Zebrafish has been advocated as an alternative animal model to study lymphocyte development, although the similarities in the genetic requirements of lymphopoiesis between fish and mammals have not yet been investigated. In this study, we examine the role of the transcription factor Ikaros in zebrafish lymphopoiesis. In fish larvae homozygous for an ikaros allele predicted to lack the C-terminal zinc fingers, T lymphopoiesis is absent; the presence of V(H)DmuJmu rearrangements in adolescent fish is delayed in mutants. In adolescent mutant fish, T cells expressing tcrb and tcrd and B cells expressing igm are formed with low efficiency and display an oligoclonal Ag receptor repertoire. By contrast, B cells expressing the igz isotype do not develop, providing genetic evidence for two separate B cell lineages in zebrafish. Thus, Ikaros appears to play similar roles in fish and mammalian lymphopoiesis.

Alleles↗

A formative model for student nurse development and evaluation--Part 1--Developing the model.

Preparing student nurses for the profession is a complex task for nurse educators; especially when dealing with the development of personal and interpersonal skills, qualities and values held in high esteem by the nursing profession and the community they serve. These researchers developed a model for formative evaluation of students by using the principles of inductive and deductive reasoning. This model was implemented in clinical practice situations and evaluated for its usefulness. It seems that the model enhanced the standards of nursing care because it had a positive effect on the behavior of students and they were better motivated; the model also improved interpersonal relationships and communication between practising nurses and students. The fact that students repeatedly use the model as a norm for self evaluation ensures that they are constantly reminded of the standards required of a professional nurse.

Clinical Competence↗

[Development of an instrument to measure self-care agency for the chronic ill in later adulthood--the first step of development].

The purpose of this study was to develop the instrument to measure self-care agency for the Japanese chronic ill in later adulthood and to test reliability and validity of that. First, the Self-Care Agency instrument draft which consists of 56 items rated along a 5-point Likert scale was developed. This draft was based upon the work of Orem (1991) and qualitative data of the Japanese chronic patients. Second, reliability and validity of this instrument was tested. The instrument was reviewed by 5 expert nurses and 16 nursing researchers for content validity. And this instrument was reviewed by 19 Japanese chronic patients for face validity. By result of content validity and face validity, this draft was refined. Next, the internal consistency, stability, and construct validity of this refined instrument was tested. The internal consistency of the instrument, as measured by the Cronbach's alpha, was 0.90 for a sample of 200 Japanese chronic patients. This instrument had a test-retest coefficient of r = 0.86 for a sample of 104 Japanese chronic patients. Using factor analytic techniques, five subscales emerged. These subscales gave some agreement with subscales that had been obtained before factor analysis. Therefore, construct validity of the instrument was established in some degree. And the subscale 'get a valid support' which emerged in this instrument was reflect Japanese cultural factor. Reliability and validity of this instrument were obtained in some degree. Further, it is necessary to refine this instrument, considering this research result.

Adult↗

Muscarinic drugs affect cholinesterase activity and development of eye structures during early chick development.

During neurogenesis, markers of the cholinergic system are present in the eye and visual cortex of vertebrates. In adult vertebrates, a role for these molecules, including muscarinic acetylcholine receptors (mAChRs), in eye growth non-accommodative regulation is also known. In order to understand the biological mechanisms triggered by the cholinergic system in these events, we analysed the effects of a cholinergic agonist (10(-4) M carbachol) and an antagonist (10(-4) M atropine) of the muscarinic receptors, on early chick development. To establish if the cholinergic system also plays a role in the regulation of early neurogenetic signals, the drug treatments were made at stage 5-6 HH, during the formation of the cephalic process. Specific effects on forehead, and in particular on eye development were found; carbachol treated embryos presented huge and well pigmented eyes, significantly different from controls. The eyes of atropine-exposed embryos presented anomalies with different phenotypes ranging from strongly affected features to normal-like appearance. Generally, the eyes were smaller as compared to the controls, with a number of anomalies, also in the normal-like phenotype, including retina and lens defects. In these structures, distribution of cholinesterase activities was checked by histochemical methods, and the amount of cells undergoing nuclear disgregation was revealed by DAPI staining. We propose that the drugs affected the known nervous and pre-nervous functions of the cholinergic markers, such as cell signalling during primary induction, and regulation of cell death by ACh receptors.

Acetylcholinesterase↗

Issues in health plan development: a critique of the guidelines for plan development under PL 93-641.

The draft guidelines for development of health systems plans and annual implementation plans represent a logical, coherent integration of the best of currently available planning concepts and methods. However, there are at least six major areas in which the current state of the art is clearly inadequate. These are linkages between plan components, synchronization, plan integration, level of detail, cross-impact analyses and policy planning. This article describes each of these issues and identifies some of the projects which seem likely to contribute to their resolution. Finally, it urges each health planning agency to take advantage of the latitude in the guidelines to develop innovative solutions and to share the results with others.

Decision Making↗

Funding of health-related facilities and other projects under the Public Works and Development Facilities Program--Economic Development Administration. Interim rule.

This interim rule modifies two regulations setting forth requirements for funding certain types of projects under the Public Works and Development Facilities Program. One regulation is amended to clarify its scope by noting that its requirements apply to Public Works Impact Program projects. The other regulation is amended to tighten its standards relating to economic impact and to specify that projects involving health-related facilities must be reviewed and approved by the Department of Health and Human Services and, if appropriate, the State Health Planning and Development Agency. In addition, a third regulation regarding project modification is amended to clarify the scope of one provision.

Financing, Government↗

Integrating knowledge and behavior: development of a management and career development program for graduate health administration education.

How best to integrate cognitive learning and behavioral skills in health administration education has been a concern of both academics and practitioners for many years. Charged with the education of health care administrators, graduate programs are expected to produce persons who are both knowledgeable about the field in which they plan to be employed and skilled in carrying out the many tasks associated with successful performance in their future roles. This article describes the theoretical basis and design of the management and career development offering (MCDO) of Widener University's Graduate Program in Health and Medical Services Administration, the key objectives of which are to integrate cognitive learning with practical experience and to provide a mechanism for the development of needed professional skills in a low-risk academic atmosphere. It was clear that these objectives could not be achieved entirely within a traditional academic curriculum, nor were they always appropriately treated there. However, the complexity of the health care field, the growing demands placed on administrators, and conflicts arising within and between roles increase the necessity to integrate these theoretical and behavioral skills.

Behavior↗

[Development of molecular targeting drugs for the treatment of cancer-therapeutic potential and issues to be addressed in global development].

A survey of cancer treatment in a sample of hospitals > 100 beds conducted in 1998 compared with experience in the US showed that good progress has been achieved in Japan in the screening and early treatment of gastric cancer, and that the prognosis for breast cancer is better than in the West. Although in the past, the cytotoxic therapies available to physicians in Japan vs the West have been different, recent acceleration of regulatory review will result in a convergence of treatment paradigms and some improvement in acute response in many tumour types. However, world wide there is a need for new improved therapies in all cancers evaluated. Particular needs are in the management of NSCLC, advanced disease and cancers which form micrometastases. The eventual hope is that cancer can be turned from a lethal disease into a chronic disease where patients maintain a good QOL. Apart from anti hormonal therapies, the usual approach has been to kill the cancerous cells. However, the new approaches to intervening in the growth and migration of cancerous cells or the host tissue response by molecular targeting offer the promise of achieving a step change in therapy. Although EGF tyrosine Kinase inhibitors such as ZD 1839 have been shown to cause a conventional tumour response in NSCLC, many of these new approaches are unlikely to show a short term response even if they have the capacity to affect tumour development and increase disease free survival. Some compounds will require combination therapy with a conventional cytotoxic or radiotherapy to show their full benefit. For conventional cytotoxics, the usual approach to development has been to select the maximum tolerated dose and then evaluate the efficacy in advanced disease. However, for the new approaches which will not have such severe dose limiting toxicities, it will be necessary to select a surrogate marker of the intended biological effect to select the optimal biological dose (OBD) and dose regimen in phase I/II studies for further evaluation in phase II or III studies which are designed to show the expected patient benefit. The tumour target, the stage of the disease and the possible need for concomitant therapy will also have to be considered according to the mechanism of action of the product.

Angiogenesis Inhibitors↗

Development of hemorheology: perspective in instrumentation development.

New viscometers for blood viscometry, improved intravital microscope, and related instruments, which are capable of measuring important rheological factors for microcirculatory research were developed and applied for hemorheological studies. As the results, four major determinants of the suspension viscosity were determined and the role of suspension viscosity of the blood as a function of microcirculatory flow was clarified. Meanwhile, the use of fluorescence microscopy and digitized video microscopic techniques has allowed the investigation of the structure and function of cells at the level of the single intact living cell. In addition, the developments and applications of laser confocal microscopy provided for not only three-dimensional image construction, but also four-dimensional image construction. In recent years, the dramatic advances in molecular biology and instrumental technology have made it possible to probe the structural and functional bases of cellular events at the molecular level. The ultimate understanding of biorheological behavior is dependent upon a molecular basis. In the future, the use of molecular biological techniques and nanotechnology (e.g., laser tweezers, atomic force microscopy and near-field microscopy, etc.) will allow the understanding of normal and abnormal rheological properties of cells, tissues, organs, and systems at the molecular level, and will contribute to progress in biomedical science.

Animals↗

Increased activity of choline acetyltransferase and acetylcholinesterase in developing cultures of chick spinal cord: a correlation with morphological development.

Explants of 10-12-day-old embryonic chick spinal cord were cultured for up to 20 days by the "coverslip-roller" method. Morphological development of neurons as shown by the presence of mature neurons, myelinated axons and synaptic structures, was demonstrated by light and electron microscopy. Two important enzymes associated with acetylcholine transmitter metabolism, choline acetyltransferase (ChAc) and acetylcholinesterase (AChE), were assayed in cultures at selected time intervals. The activity of ChAc and AChE exhibited an increase of 60 per cent and 80 per cent, respectively, over a 20-day period. It is concluded that organotypic cultures of embryonic chick spinal cord show differentiation not only in morphological aspects, but also in biochemical terms through progressive development of ChAc and AChE.

Acetylcholinesterase↗

[Guideline development for general medicine: the problem of dichotomized algorithm development].

Development of clinical guidelines in Germany is based on two divergent principles. One is the clinical position of individuality and clinical experience. The other is the strong adherence to the principles of evidence-based medicine and the scientific method, as demonstrated by the clear, algorithmic methodology of critical pathway development. We discuss the pros and cons of both concepts and try to find some sort of practical middle ground between the two extremes.

Algorithms↗

[Development of righting reflexes and their influence on the development of static functions in children with infantile cerebral palsy].

In a group of 55 children with signs of central nervous system lesions the development of righting reflexes and static functions was observed during the first 3 years of life. A delay and disturbances in the development of righting reflexes and static functions was observed with differences between the individual groups of infantile cerebral palsy.

Age Factors↗