Photophysical studies of zinc phthalocyanine and chloroaluminum phthalocyanine incorporated into liposomes in the presence of additives

The photophysical properties of zinc phthalocyanine (ZnPC) and chloroaluminum phthalocyanine (AlPHCl) incorporated into liposomes of dimyristoyl phosphatidylcholine in the presence and absence of additives such as cholesterol or cardiolipin were studied by time-resolved fluorescence, laser flash photolysis and steady-state techniques. The absorbance of the drugs changed linearly with drug concentration, at least up to 5.0 µM in homogeneous and heterogeneous media, indicating that aggregation did not occur in these media within this concentration range. The incorporation of the drugs into liposomes increases the dimerization constant by one order of magnitude (for ZnPC, 3.6 x 10(4) to 1.0 x 10(5) M-1 and for AlPHCl, 3.7 x 10(4) to 1.5 x 10(5) M-1), but this feature dose does not rule out the use of this carrier, since the incorporation of these hydrophobic drugs into liposomes permits their systemic administration. Probe location in biological membranes and predominant positions of the phthalocyanines in liposomes were inferred on the basis of their fluorescence and triplet state properties. Both phthalocyanines are preferentially distributed in the internal regions of the liposome bilayer. The additives affect the distribution of these drugs within the liposomes, a fact that controls their delivery when both are used in a biological medium, retarding their release. The addition of the additives to the liposomes increases the internalization of phthalocyanines. The interaction of the drugs with a plasma protein, bovine serum albumin, was examined quantitatively by the fluorescence technique. The results show that when the drugs were incorporated into small unilamellar liposomes, the association with albumin was enhanced when compared with organic media, a fact that should increase the selectivity of tumor targeting by these phthalocyanines (for ZnPC, 0.71 x 10(6) to 1.30 x 10(7) M-1 and for AlPHCl, 4.86 x 10(7) to 3.10 x 10(8) M-1).

Antagonist G-mediated targeting and cytotoxicity of liposomal doxorubicin in NCI-H82 variant small cell lung cancer

The aim of the present study was to characterize the interactions of antagonist G (H-Arg-D-Trp-NmePhe-D-Trp-Leu-Met-NH 2)-targeted sterically stabilized liposomes with the human variant small cell lung cancer (SCLC) H82 cell line and to evaluate the antiproliferative activity of encapsulated doxorubicin against this cell line. Variant SCLC tumors are known to be more resistant to chemotherapy than classic SCLC tumors. The cellular association of antagonist G-targeted (radiolabeled) liposomes was 20-30-fold higher than that of non-targeted liposomes. Our data suggest that a maximum of 12,000 antagonist G-targeted liposomes were internalized/cell during 1-h incubation at 37ºC. Confocal microscopy experiments using pyranine-containing liposomes further confirmed that receptor-mediated endocytosis occurred, specifically in the case of targeted liposomes. In any of the previously mentioned experiments, the binding and endocytosis of non-targeted liposomes have revealed to be negligible. The improved cellular association of antagonist G-targeted liposomes, relative to non-targeted liposomes, resulted in an enhanced nuclear delivery (evaluated by fluorimetry) and cytotoxicity of encapsulated doxorubicin for incubation periods as short as 2 h. For an incubation of 2 h, we report IC50 values for targeted and non-targeted liposomes containing doxorubicin of 5.7 ± 3.7 and higher than 200 µM doxorubicin, respectively. Based on the present data, we may infer that receptors for antagonist G were present in H82 tumor cells and could mediate the internalization of antagonist G-targeted liposomes and the intracellular delivery of their content. Antagonist G covalently coupled to liposomal drugs may be promising for the treatment of this aggressive and highly heterogeneous disease.

Assessment of tidal volume and thoracoabdominal motion using volume and flow-oriented incentive spirometers in healthy subjects

The objective of the present study was to evaluate incentive spirometers using volume- (Coach and Voldyne) and flow-oriented (Triflo II and Respirex) devices. Sixteen healthy subjects, 24 ± 4 years, 62 ± 12 kg, were studied. Respiratory variables were obtained by respiratory inductive plethysmography, with subjects in a semi-reclined position (45º). Tidal volume, respiratory frequency, minute ventilation, inspiratory duty cycle, mean inspiratory flow, and thoracoabdominal motion were measured. Statistical analysis was performed with Kolmogorov-Smirnov test, t-test and ANOVA. Comparison between the Coach and Voldyne devices showed that larger values of tidal volume (1035 ± 268 vs 947 ± 268 ml, P = 0.02) and minute ventilation (9.07 ± 3.61 vs 7.49 ± 2.58 l/min, P = 0.01) were reached with Voldyne, whereas no significant differences in respiratory frequency were observed (7.85 ± 1.24 vs 8.57 ± 1.89 bpm). Comparison between flow-oriented devices showed larger values of inspiratory duty cycle and lower mean inspiratory flow with Triflo II (0.35 ± 0.05 vs 0.32 ± 0.05 ml/s, P = 0.00, and 531 ± 137 vs 606 ± 167 ml/s, P = 0.00, respectively). Abdominal motion was larger (P < 0.05) during the use of volume-oriented devices compared to flow-oriented devices (52 ± 11% for Coach and 50 ± 9% for Voldyne; 43 ± 13% for Triflo II and 44 ± 14% for Respirex). We observed that significantly higher tidal volume associated with low respiratory frequency was reached with Voldyne, and that there was a larger abdominal displacement with volume-oriented devices.

Psykoosipotilaille tarkoitetun sähköisen potilasopetusmentelmän levitys ja mielenterveystyön ammattilaisten kokemuksia käytöstä

Tämän laadullisen tutkimuksen tarkoituksena oli kuvata psykoosipotilaille tarkoitetun sähköisen potilasopetusmentelmän (MieliNet) levitystä sekä sosiaali- ja terveydenhuollon psykiatristen toimintayksiköiden mielenterveystyön ammattilaisten kokemuksia sähköisen potilasopetusmenetelmän käytöstä. Tutkimuksen tavoitteena on saatavan tiedon avulla kehittää edelleen MieliNet-ohjelman hyödynnettävyyttä psykiatrisessa hoitotyössä. Tutkimusaineisto kerättiin kolmessa vaiheessa. Ensimmäisessä vaiheessa selvitettiin sosiaali- ja terveydenhuollon psykiatristen toimintayksiköiden (n = 125) kiinnostusta tutustua sähköiseen potilasopetukseen. Potilasopetuksesta kiinnostuneiden organisaatioiden (n = 16) taustatiedot kuvattiin sekä selvitettiin mielenterveystyön ammattilaisten (n = 41) halukkutta tutustua MieliNet-sivustoon ja osallistua sähköisen potilasopetuksen verkkokurssille. Toisessa ja kolmannessa vaiheessa aineisto kerättiin sähköiselle moodle-alustalle sähköisen potilasopetusmenetelmän koekäyttäjiltä (n=7). Aineisto analysoitiin induktiivista ja deduktiivista sisällön analyysiä käyttäen. Tutkimustulosten mukaan sähköisestä potilasopetusmenetelmästä kiinnostuneiden organisaatioiden osuus oli 4% niistä organisaatioista, joille tiedon levitys tapahtui. Sähköisen potilasopetusmenetelmän koekäyttäjistä valtaosa työskenteli erikoissairaanhoidossa toimivissa aikuispsykiatrian avohoidon yksiköissä. Sähköisen potilasopetusmenetelmän käytön vahvuuksina koettiin potilasopetuksen tehostuminen, omahoitajasuhteen kehittyminen ja potilaiden lisääntynyt hoitoon sitoutuminen. Heikkouksina koettiin ongelmat sähköisen potilasopetusohjelman käytössä ja ennakkoluulot sähköisen potilasopetusohjelman käytöstä sekä potilaiden psyykkisen voinnin heikentyminen. Mahdollisuuksina koettiin potilasopetuksen tehostuminen ja potilasopetusohjelman uudet käyttömahdollisuudet. Uhkina koettiin sähköisen potilasopetusmenetelmän riittämätön arvostus sekä ongelmat ja ennakkoluulot potilasopetusohjelman käytössä. Potilaiden yksilöllisyys huomioitiin hyvin potilasopetustilanteissa. Sähköinen potilasopetusmenetelmä synnytti keskustelua potilaille tärkeistä asioista. Potilasopetustilanteiden sujuminen, potilaiden asenne ja oma osaaminen aiheuttivat huolta. Potilasopetustilanteisiin valmistautumiseen halutaan jatkossa kiinnittää enemmän huomiota.

Breathing pattern, thoracoabdominal motion and muscular activity during three breathing exercises

The objective of the present study was to evaluate breathing pattern, thoracoabdominal motion and muscular activity during three breathing exercises: diaphragmatic breathing (DB), flow-oriented (Triflo II) incentive spirometry and volume-oriented (Voldyne) incentive spirometry. Seventeen healthy subjects (12 females, 5 males) aged 23 ± 5 years (mean ± SD) were studied. Calibrated respiratory inductive plethysmography was used to measure the following variables during rest (baseline) and breathing exercises: tidal volume (Vt), respiratory frequency (f), rib cage contribution to Vt (RC/Vt), inspiratory duty cycle (Ti/Ttot), and phase angle (PhAng). Sternocleidomastoid muscle activity was assessed by surface electromyography. Statistical analysis was performed by ANOVA and Tukey or Friedman and Wilcoxon tests, with the level of significance set at P < 0.05. Comparisons between baseline and breathing exercise periods showed a significant increase of Vt and PhAng during all exercises, a significant decrease of f during DB and Voldyne, a significant increase of Ti/Ttot during Voldyne, and no significant difference in RC/Vt. Comparisons among exercises revealed higher f and sternocleidomastoid activity during Triflo II (P < 0.05) with respect to DB and Voldyne, without a significant difference in Vt, Ti/Ttot, PhAng, or RC/Vt. Exercises changed the breathing pattern and increased PhAng, a variable of thoracoabdominal asynchrony, compared to baseline. The only difference between DB and Voldyne was a significant increase of Ti/Ttot compared to baseline. Triflo II was associated with higher f values and electromyographic activity of the sternocleidomastoid. In conclusion, DB and Voldyne showed similar results while Triflo II showed disadvantages compared to the other breathing exercises.

Breathing pattern and thoracoabdominal motion during exercise in chronic obstructive pulmonary disease

Subjects with chronic obstructive pulmonary disease (COPD) present breathing pattern and thoracoabdominal motion abnormalities that may contribute to exercise limitation. Twenty-two men with stable COPD (FEV1 = 42.6 ± 13.5% predicted; age 68 ± 8 years; mean ± SD) on usual medication and with at least 5 years of diagnosis were evaluated at rest and during an incremental cycle exercise test (10 watts/2 min). Changes in respiratory frequency, tidal volume, rib cage and abdominal motion contribution to tidal volume and the phase angle that measures the asynchrony were analyzed by inductive respiratory plethysmography at rest and during three levels of exercise (30-50, 70-80, and 100% maximal work load). Repeated measures ANOVA followed by pre-planned contrasts and Bonferroni corrections were used for analyses. As expected, the greater the exercise intensity the higher the tidal volume and respiratory frequency. Abdominal motion contributed to the tidal volume increase (rest: 49.82 ± 11.19% vs exercise: 64.15 ± 9.7%, 63.41 ± 10%, and 65.56 ± 10.2%, respectively, P < 0.001) as well as the asynchrony [phase angle: 11.95 ± 7.24° at rest vs 22.2 ± 15° (P = 0.002), 22.6 ± 9° (P < 0.001), and 22.7 ± 8° (P < 0.001), respectively, at the three levels of exercise]. In conclusion, the increase in ventilation during exercise in COPD patients was associated with the major motion of the abdominal compartment and with an increase in the asynchrony independent of exercise intensity. It suggests that cycling exercise is an effective way of enhancing ventilation in COPD patients.

Effect of melatonin and time of administration on irradiation-induced damage to rat testes

The effect of ionizing irradiation on testes and the protective effects of melatonin were investigated by immunohistochemical and electron microscopic methods. Eighty-two adult male Wistar rats were divided into 10 groups. The rats in the irradiated groups were exposed to a sublethal irradiation dose of 8 Gy, either to the total body or abdominopelvic region using a 60Co source at a focus of 80 cm away from the skin in the morning or evening together with vehicle (20% ethanol) or melatonin administered 24 h before (10 mg/kg), immediately before (20 mg/kg) and 24 h after irradiation (10 mg/kg), all ip. Caspace-3 immunoreactivity was increased in the irradiated group compared to control (P < 0.05). Melatonin-treated groups showed less apoptosis as indicated by a considerable decrease in caspace-3 immunoreactivity (P < 0.05). Electron microscopic examination showed that all spermatogenic cells, especially primary spermatocytes, displayed prominent degeneration in the groups submitted to total body and abdominopelvic irradiation. However, melatonin administration considerably inhibited these degenerative changes, especially in rats who received abdominopelvic irradiation. Total body and abdominopelvic irradiation induced identical apoptosis and testicular damage. Chronobiological assessment revealed that biologic rhythm does not alter the inductive effect of irradiation. These data indicate that melatonin protects against total body and abdominopelvic irradiation. Melatonin was more effective in the evening abdominopelvic irradiation and melatonin-treated group than in the total body irradiation and melatonin-treated group.

Effect of neoadjuvant chemotherapy on low-density lipoprotein (LDL) receptor and LDL receptor-related protein 1 (LRP-1) receptor in locally advanced breast cancer

Low-density lipoprotein (LDL) receptors are overexpressed in most neoplastic cell lines and provide a mechanism for the internalization and concentration of drug-laden nanoemulsions that bind to these receptors. The aim of the present study was to determine whether the administration of standard chemotherapeutic schemes can alter the expression of LDL and LDL receptor-related protein 1 (LRP-1) receptors in breast carcinoma. Fragments of tumoral and normal breast tissue from 16 consecutive volunteer women with breast cancer in stage II or III were obtained from biopsies before the beginning of neoadjuvant chemotherapy and after chemotherapy, from fragments excised during mastectomy. Tissues were analyzed by immunohistochemistry for both receptors. Because complete response to treatment was achieved in 4 patients, only the tumors from 12 were analyzed. Before chemotherapy, there was overexpression of LDL receptor in the tumoral tissue compared to normal breast tissue in 8 of these patients. LRP-1 receptor overexpression was observed in tumors of 4 patients. After chemotherapy, expression of both receptors decreased in the tumors of 6 patients, increased in 4 and was unchanged in 2. Nonetheless, even when chemotherapy reduced receptors expression, the expression was still above normal. The fact that chemotherapy does not impair LDL receptors expression supports the use of drug carrier systems that target neoplastic cells by the LDL receptor endocytic pathway in patients on conventional chemotherapy.

Tissue transglutaminase (TG2) activity regulates osteoblast differentiation and mineralization in the SAOS-2 cell line

Tissue transglutaminase (type II, TG2) has long been postulated to directly promote skeletal matrix calcification and play an important role in ossification. However, limited information is available on the expression, function and modulating mechanism of TG2 during osteoblast differentiation and mineralization. To address these issues, we cultured the well-established human osteosarcoma cell line SAOS-2 with osteo-inductive conditioned medium and set up three time points (culture days 4, 7, and 14) to represent different stages of SAOS-2 differentiation. Osteoblast markers, mineralization, as well as TG2 expression and activity, were then assayed in each stage. Furthermore, we inhibited TG activity with cystamine and then checked SAOS-2 differentiation and mineralization in each stage. The results showed that during the progression of osteoblast differentiation SAOS-2 cells presented significantly high levels of osteocalcin (OC) mRNA, bone morphogenetic protein-2 (BMP-2) and collagen I, significantly high alkaline phosphatase (ALP) activity, and the increased formation of calcified matrix. With the same tendency, TG2 expression and activity were up-regulated. Furthermore, inhibition of TG activity resulted in a significant decrease of OC, collagen I, and BMP-2 mRNA and of ALP activity and mineralization. This study demonstrated that TG2 is involved in osteoblast differentiation and may play a role in the initiation and regulation of the mineralization processes. Moreover, the modulating effects of TG2 on osteoblasts may be related to BMP-2.

The way to organizational longevity - Balancing stability and change in Shinise firms

THE WAY TO ORGANIZATIONAL LONGEVITY – Balancing stability and change in Shinise firms The overall purpose of this dissertation is to investigate the secret of longevity in Shinise firms. On the basic assumption that organizational longevity is about balancing stability and change, the theoretical perspectives incorporate routine practice, organizational culture, and organizational identity. These theories explain stability and change in an organization separately and in combination. Qualitative inductive theory building was used in the study. Overall, the empirical data comprised 75 in-depth and semi-structured interviews, 137 archival materials, and observations made over 17 weeks. According to the empirical findings, longevity in Shinise firms is attributable to the internal mechanisms (Shinise tenacity, stability in motion, and emergent change) to secure a balance between stability and change, the continuing stability of the socio-cultural environment in the local community, and active interaction between organizational and local cultures. The contribution of the study to the literature on organizational longevity and the alternative theoretical approaches is first, in theorizing the mechanisms of Shinise tenacity and cross-level cultural dynamism, and second, in pointing out the critical role of: the way firms set their ultimate goal, the dynamism in culture, and the effect of history of the firm to the current business in securing longevity. KEY WORDS Change; Culture; Organizational identity; Organizational longevity; Routines; Shinise firms; Stability; Qualitative research

The challenges and successful strategies of secondary school administrators /

This study presents information gathered during personal interviews in the area of challenges that administrators have faced in their careers, and the strategies they have found to be successful in meeting those challenges. This research is a qualitative study, using an inductive approach. Five participants were chosen, based on convenience sampling, with semi-structured interviews that were audio recorded. The theoretical research found that school violence and stafS'school morale were key challenges facing administrators, with a variety of approaches suggested to foster success in meeting those challenges. Some of these approaches included knowledge, team work, an ethic of care, and having a school vision. From the interviews it became clear that the challenges administrators faced included those posed by students, including disciplinary issues, those posed by adults and those posed by government changes in education. In regards to strategies for success, the interviews revealed three key concepts that were emphasized as vital. These were the assets of craft knowledge (experience), collegiality, and the use of other professional resources and educators.

Exploring the events that engage graduate students in transformative learning /

This research explored the events that engaged graduate students in transformative learning within a graduate program in education. This context was chosen because one objective of a graduate program is to facilitate critical thinking and transformative learning. The question ofhow adult learners perceive and experience learning steered the direction ofthis study. However, the purpose ofthis research was to study critical incidents that led to profound cognitive and affective changes as perceived by the graduate students. Specifically, the questions to be answered were what critical incidents happened to graduate students while in the Master ofEducation program, how were the incidents experienced, and what transformation resulted? The research design evolved over the course of a year and was highly influenced by previous empirical studies and criticisms oftransformative learning theory. The overall design was qualitative and phenomenological. A critical and interpretive approach was made to empirical data collected through a critical incident questionnaire and in-depth interviews. Inductive analysis allowed theory to be built from the data by making comparisons. New questions emerged and attention was given to social context, the passage oftime, and sequence ofevents in order to give meaning and translation ofthe participants' experiences and to build the interpretive narratives. Deductive analysis was also used on the data and a blending ofthe two forms of analysis; this resulted in the development ofa foundational model for transformative learning to be built.The data revealed critical incidents outside ofthe graduate school program that occurred in childhood or adult life prior to graduate school. Since context of individuals' lives had been an important critique of past transformative learning models and studies, this research expanded the original boundaries of this study beyond graduate school to incorporate incidents that occurred outside of graduate school. Critical incidents were categorized into time-related, people-related, and circumstancerelated themes. It was clear that participants were influenced and molded by the stage oftheir life, personal experiences, familial and cultural conditioning, and even historic events. The model developed in this document fiom an overview ofthe fmdings identifies a four-stage process of life difficulty, disintegration, reintegration, and completion that all participants' followed. The blended analysis was revealed from the description ofhow the incidents were experienced by the participants. The final categories were what were the feelings, what was happening, and what was the enviromnent? The resulting transformation was initially only going to consider cognitive and affective changes, however, it was apparent that contextual changes also occurred for all participants, so this category was also included. The model was described with the construction metaphor of a building "foimdation" to illustrate the variety of conditions that are necessary for transformative learning to occur. Since this was an exploratory study, no prior models or processes were used in data analysis, however, it appeared that the model developed from this study incorporated existing models and provided a more encompassing life picture oftransformative learning.

Female administrators and the mentors who give them full support /

A looming attrition rate, a steady increase in the number of women in administration, and a lack of Canadian research all provided the rationale for this study. The problem in this study was to investigate the needs and challenges of new female administrators and to examine the role that mentors play in addressing these issues. This study also explored the perceived benefits of having a mentor. This study examined the inductive year of 33 female administrators from 3 Ontario school boards. It was a qualitative and quantitative design, using questionnaire and interview data. It was found that the majority felt that they struggled with biases and expectations that were gender specific. The challenges that were perceived to be most prevalent were categorized into 4 thematic areas: Maintaining Balance, Feeling Pressured, The Perceptions of Others, and Being Challenged by Others. Regarding the benefits of mentoring, the participants perceived mentoring to be most beneficial in terms of professional growth, followed by learning how to run a school, and then career advancement. The significance of this study was threefold: it had theoretical implications as well as implications for practice and future research. Suggestions included: facilitating longitudinal relationships, having the board become more actively involved in facilitating the relationship, and implementing an internship program. This study attempted to extend the current literature by theorizing that a mentorship is cyclical in nature. Future research could include program design and implementation, as well as providing consistent and accessible mentoring opportunities for all.

From the ground up : understanding how teachers and administrators make sense of tension

Strategies designed to improve educational systems have created tensions in school personnel as they struggle to respond to competing demands of ongoing change within their daily realities. The purpose of this case study was to investigate how teachers and administrators in one elementary school made sense ofthese tensions and to explore the factors that constrained or shaped their responses. A constructive interpretative case study using a grounded theory approach was used. Qualitative data were collected through document analysis, semi-structured interviews, and participant observation. In-depth information about teachers' and administrators' experiences and a contextual understanding oftension was generated from inductive analysis of the data. The study found that tension was a phenomenon situated in the context in which it arose. A contextual understanding of tension revealed the interactions between the institutional, personal, and emotional domains that continually shaped individual and group behavioural responses. This contextual understanding of tension provided the means to reinterpret resistance to change. It also helped to show how teachers and administrators reconstructed identities and made sense in context.. Of particular note was the crucial nature of the conditions under which teachers and adlninistrators shaped meaning and understood change. This study sheds light on the contextual intricacies of tension that may help leaders with the complex design and implementation of educational change..

A speculative systems model of the dynamic interaction among students, faculty and administration in the community college, with particular reference to intrinsic motivation and the teacher-administrator interface

The challenge the community college faces in helping meet the needs of the living open system of society is examined in this study. It is postulated that internalization student outcomes are required by society to reduce entropy and remain self-renewing. Such behavior is characterized as having an intrinsically motivated energy source and displays the seeking and conquering of challenge, the development of reflective knowledge and skill, full use of all capabilities, internal control, growth orientation, high self-esteem, relativistic thinking and competence. The development of a conceptual systems model that suggests how transactions among students, faculty and administration might occur to best meet the needs of internalization outcomes in students, and intrinsic motivation in faculty is a major purpose of this study. It is a speculative model that is based on a synthesis of a wide variety of variables. Empirical evidence, theoretical considerations, and speculative ideas are gathered together from researchers and theoretici.ans who are working on separate answers to questions of intrinsic motivation, internal control and environments that encourage their development. The model considers the effect administrators·have on faculty anq the corresponding effect faculty may have on students. The major concentration is on the administrator--teacher interface.For administrators the model may serve as a guide in planning effective transactions, and establishing system goals. The teacher is offered a means to coordinate actions toward a specific overall objective, and the administrator, teacher and researcher are invited to use the model to experiment, innovate, verify the assumptions on which the model is based, and raise additional hypotheses. Goals and history of the community colleges in Ontario are examined against current problems, previous progress and open system thinking. The nature of the person as a five part system is explored with emphasis on intrinsic motivation. The nature, operation, conceptualization, and value of this internal energy source is reviewed in detail. The current state of society, education and management theory are considered and the value of intrinsically motivating teaching tasks together with "system four" leadership style are featured. Evidence is reviewed that suggests intrinsically motivated faculty are needed, and "system four" leadership style is the kind of interaction-influence system needed to nurture intrinsic motivation in faculty.