Synthesis of mucoadhesive thiol-bearing microgels from 2-(acetylthio)ethylacrylate and 2-hydroxyethylmethacrylate: novel drug delivery systems for chemotherapeutic agents to the bladder

Thiol-bearing microgels have been synthesised from copolymerisation of 2-(acetylthio)ethylacrylate and 2-hydroxyethylmethacrylate, and subsequent deprotection using sodium thiomethoxide. The concentration of thiol groups on these microgels could be tailored by use of different molar ratios of the two monomers. These thiol-bearing microgels were shown to adhere to ex vivo porcine urinary bladder, which was correlated with their level of thiolation. By simply mixing solutions of thiol-bearing microgels and doxorubicin, high levels of drug loading into the microgels could be achieved. Thiol-bearing microgels controlled the release of doxorubicin in a time-dependent manner over several hours. These doxorubicin-loaded thiol-bearing microgels could have application in the treatment of early-stage bladder cancers. The method used represents a new ‘bottom-up’ approach for the synthesis of novel mucoadhesive microgels.

An investigation of the required skills for the delivery of low and zero carbon buildings within a region

The United Kingdom is committed to a raft of requirements to create a low-carbon economy. Buildings consume approximately 40% of UK energy demand. Any improvement on the energy performance of buildings therefore can significantly contribute to the delivery of a low-carbon economy. The challenge for the construction sector and its clients is how to meet the policy requirements to deliver low and zero carbon (LZC) buildings, which spans broader than the individual building level, to requirements at the local and regional levels, and wider sustainability pressures. Further, the construction sector is reporting skills shortages coupled with the need for ‘new skills’ for the delivery of LZC buildings. The aim of this paper is to identify, and better understand, the skills required by the construction sector and its clients for the delivery of LZC buildings within a region. The theoretical framing for this research is regional innovation system (RIS) using a socio-technical network analysis (STNA) methodology. A case study of a local authority region is presented. Data is drawn from a review of relevant local authority documentation, observations and semi-structured interviews from one (project 1) of five school retrofit projects within the region. The initial findings highlight the complexity surrounding the form and operation of the LZC network for project 1. The skills required by the construction sector and its clients are connected to different actor roles surrounding the delivery of the project. The key actors involved and their required skills are: project management and energy management skills required by local authority; project management skills (in particular project planning), communication and research skills required by school end-users; and a ‘technical skill’ relating to knowledge of a particular energy efficient measure (EEM) and use of equipment to implement the EEM is required by the EEM contractors.

In situ gelling systems based on Pluronic F127/Pluronic F68 formulations for ocular drug delivery

This study evaluated the use of Pluronic F127 and Pluronic F68 as excipients for formulating in situ gelling systems for ocular drug delivery. Thermal transitions have been studied in aqueous solutions of Pluronic F127, Pluronic F68 as well as their binary mixtures using differential scanning calorimetry, rheological measurements, and dynamic light scattering. It was established that the formation of transparent gels at physiologically relevant temperatures is observed only in the case of 20 wt % of Pluronic F127. The addition of Pluronic F68 to Pluronic F127 solutions increases the gelation temperature of binary formulation to above physiological range of temperatures. The biocompatibility evaluation of these formulations using slug mucosa irritation assay and bovine corneal erosion studies revealed that these polymers and their combinations do not cause significant irritation. In vitro drug retention study on glass surfaces and freshly excised bovine cornea showed superior performance of 20 wt % Pluronic F127 compared to other formulations. In addition, in vivo studies in rabbits demonstrated better retention performance of 20 wt % Pluronic F127 compared to Pluronic F68. These results confirmed that 20 wt % Pluronic F127 offers an attractive ocular formulation that can form a transparent gel in situ under physiological conditions with minimal irritation.

Cross layer based protocols for energy aware and critical data delivery related applications using wireless sensor networks

Wireless Sensor Networks (WSNs) have been an exciting topic in recent years. The services offered by a WSN can be classified into three major categories: monitoring, alerting, and information on demand. WSNs have been used for a variety of applications related to the environment (agriculture, water and forest fire detection), the military, buildings, health (elderly people and home monitoring), disaster relief, and area or industrial monitoring. In most WSNs tasks like processing the sensed data, making decisions and generating emergency messages are carried out by a remote server, hence the need for efficient means of transferring data across the network. Because of the range of applications and types of WSN there is a need for different kinds of MAC and routing protocols in order to guarantee delivery of data from the source nodes to the server (or sink). In order to minimize energy consumption and increase performance in areas such as reliability of data delivery, extensive research has been conducted and documented in the literature on designing energy efficient protocols for each individual layer. The most common way to conserve energy in WSNs involves using the MAC layer to put the transceiver and the processor of the sensor node into a low power, sleep state when they are not being used. Hence the energy wasted due to collisions, overhearing and idle listening is reduced. As a result of this strategy for saving energy, the routing protocols need new solutions that take into account the sleep state of some nodes, and which also enable the lifetime of the entire network to be increased by distributing energy usage between nodes over time. This could mean that a combined MAC and routing protocol could significantly improve WSNs because the interaction between the MAC and network layers lets nodes be active at the same time in order to deal with data transmission. In the research presented in this thesis, a cross-layer protocol based on MAC and routing protocols was designed in order to improve the capability of WSNs for a range of different applications. Simulation results, based on a range of realistic scenarios, show that these new protocols improve WSNs by reducing their energy consumption as well as enabling them to support mobile nodes, where necessary. A number of conference and journal papers have been published to disseminate these results for a range of applications.

Delivery of cloned offspring: experience in Zebu cattle (Bos indicus)

The production of a healthy cloned calf is dependent on a multitude of successful steps, including reprogramming mediated by the oocyte, the development of a functional placenta, adequate maternal-fetal interaction, the establishment of a physiological metabolic setting and the formation of a complete set of well-differentiated cells that will eventually result in well-characterised and fully competent tissues and organs. Although the efficiency of nuclear transfer has improved significantly since the first report of a somatic cell nuclear transfer-derived animal, there are many descriptions of anomalies concerning cloned calves leading to high perinatal morbidity and mortality. The present article discusses some our experience regarding perinatal and neonatal procedures for cloned Zebu cattle (B. indicus) that has led to improved survival rates in Nellore cloned calves following the application of such `labour-intensive technology`.

Intake, water consumption, ruminal fermentation, and stress response of beef heifers fed after different lengths of delays in the daily feed delivery time

Four rumen-fistulated Holstein heifers (134 +/- 1 kg initial BW) were used in a 4 x 4 Latin square design to determine the effects of delaying daily feed delivery time on intake, ruminal fermentation, behavior, and stress response. Each 3-wk experimental period was preceded by 1 wk in which all animals were fed at 0800 h. Feed bunks were cleaned at 0745 h and feed offered at 0800 h (T0, no delay), 0900 (T1), 1000 (T2), and 1100 (T3) from d1 to 21 with measurements taken during wk 1 and 3. Heifers were able to see each other at all times. Concentrate and barley straw were offered in separate compartments of the feed bunks, once daily and for ad libitum intake. Ruminal pH and saliva cortisol concentrations were measured at 0, 4, 8, and 12 h postfeeding on d 3 and 17 of each experimental period. Fecal glucocorticoid metabolites were measured on d 17. Increasing length of delay in daily feed delivery time resulted in a quadratic response in concentrate DMI (low in T1 and T2; P = 0.002), whereas straw DMI was greatest in T1 and T3 (cubic P = 0.03). Treatments affected the distribution of DMI within the day with a linear decrease observed between 0800 and 1200 h but a linear increase during nighttimes (2000 to 0800 h), whereas T1 and T2 had reduced DMI between 1200 and 1600 h (quadratic P = 0.04). Water consumption (L/d) was not affected but decreased linearly when expressed as liters per kilogram of DMI (P = 0.01). Meal length was greatest and eating rate slowest in T1 and T2 (quadratic P <= 0.001). Size of the first meal after feed delivery was reduced in T1 on d 1 (cubic P = 0.05) and decreased linearly on d 2 (P = 0.01) after change. Concentrate eating and drinking time (shortest in T1) and straw eating time (longest in T1) followed a cubic trend (P = 0.02). Time spent lying down was shortest and ruminating in standing position longest in T1 and T2. Delay of feeding time resulted in greater daily maximum salivary cortisol concentration (quadratic P = 0.04), which was greatest at 0 h in T1 and at 12 h after feeding in T2 (P < 0.05). Daily mean fecal glucocorticoid metabolites were greatest in T1 and T3 (cubic P = 0.04). Ruminal pH showed a treatment effect at wk 1 because of increased values in T1 and T3 (cubic P = 0.01). Delaying feed delivery time was not detrimental for rumen function because a stress response was triggered, which led to reduced concentrate intake, eating rate, and size of first meal, and increased straw intake. Increased salivary cortisol suggests that animal welfare is compromised.

Systemic delivery of adult stem cells improves cardiac function in spontaneously hypertensive rats

Heart regeneration after myocardial infarction (MI) can occur after cell therapy, but the mechanisms, cell types and delivery methods responsible for this improvement are still under investigation. In the present study, we evaluated the impact of systemic delivery of bone marrow cells (BMC) and cultivated mesenchymal stem cells (MSC) on cardiac morphology, function and mortality in spontaneously hypertensive rats (SHR) submitted to coronary occlusion. Female syngeneic adult SHR, submitted or not (control group; C) to MI, were treated with intravenous injection of MSC (MI + MSC) or BMC (MI + BM) from male rats and evaluated after 1, 15 and 30 days by echocardiography. Systolic blood pressure (SBP), functional capacity, histology, mortality rate and polymerase chain reaction for the Y chromosome were also analysed. Myocardial infarction induced a decrease in SBP and BMC, but not MSC, prevented this decrease. An improvement in functional capacity and ejection fraction (38 +/- 4, 39 +/- 3 and 58 +/- 2% for MI, MI + MSC and MI + BM, respectively; P < 0.05), as well as a reduction of the left ventricle infarcted area, were observed in rats from the MI + BM group compared with the other three groups. Treated animals had a significantly reduced lesion tissue score. The mortality rate in the C, MI + BM, MI + MSC and MI groups was 0, 0, 16.7 and 44.4%, respectively (P < 0.05 for the MI + MSC and MI groups compared with the C and MI + BM groups). The results of the present study suggest that systemic administration of BMC can improve left ventricular function, functional capacity and, consequently, reduce mortality in an animal model of MI associated with hypertension. We speculate that the cells transiently home to the myocardium, releasing paracrine factors that recruit host cells to repair the lesion.

Continuous and High-Level In Vivo Delivery of Endostatin From Recombinant Cells Encapsulated in TheraCyte (R) Immunoisolation Devices

Endostatin (ES) is a potent inhibitor of angiogenesis and tumor growth. Continuous ES delivery of ES improves the efficacy and potency of the antitumoral therapy. The TheraCyte (R) system is a polytetrafluoroethylene (PTFE) semipermeable membrane macroencapsulation system for implantation of genetically engineered cells specially designed for the in vivo delivery of therapeutic proteins, such as ES, which circumvents the problem of limited half-life and variation in circulating levels. In order to enable neovascularization at the tissues adjacent to the devices prior to ES secretion by the cells inside them, we designed a scheme in which empty TheraCyte (R) devices were preimplanted SC into immunodeficient mice. Only after healing (17 days later) were Chinese hamster ovary cells expressing ES injected into the preimplanted devices. In another model for device implantation, the cells expressing ES where loaded into the immunoisolation devices prior to implantation into the animals, and the TheraCyte (R) were then immediately implanted SC into the mice. Throughout the 2-month study, constant high ES levels of up to 3.7 mu g/ml were detected in the plasma of the mice preimplanted with the devices, while lower but also constant levels of ES (up to 2.1 mu g/ml plasma) were detected in the mice that had received devices preloaded with the ES-expressing cells. Immunohistochemistry using anti-ES antibody showed reaction within the device and outside it, demonstrating that ES, secreted by the confined recombinant cells, permeated through the membrane and reached the surrounding tissues.

Myostatin gene knockdown through lentiviral-mediated delivery of shRNA for in vitro production of transgenic bovine embryos

Myostatin is described as a negative regulator of the skeletal muscle growth. Genetic engineering, in order to produce animals with double the muscle mass and that can transmit the characteristic to future progeny, may be useful. In this context, the present study aimed to analyse the feasibility of lentiviral-mediated delivery of short hairpin RNA (shRNA) targeting of myostatin into in vitro produced transgenic bovine embryos. Lentiviral vectors were used to deliver a transgene that expressed green fluorescent protein (GFP) and an shRNA that targeted myostatin. Vector efficiency was verified through in vitro murine myoblast (C2C12) cell morphology after inductive differentiation and by means of real-time PCR. The lentiviral vector was microinjected into the perivitellinic space of in vitro matured oocytes. Non-microinjected oocytes were used as the control. After injection, oocytes were fertilized and cultured in vitro. Blastocysts were evaluated by epifluorescence microscopy. Results demonstrated that the vector was able to inhibit myostatin mRNA in C2C12 cells, as the transducted group had a less amount of myostatin mRNA after 72 h of differentiation (p < 0.05) and had less myotube formation than the non-transduced group (p < 0.05). There was no difference in cleavage and blastocyst rates between the microinjected and control groups. After hatching, 3.07% of the embryos exhibited GFP expression, indicating that they expressed shRNA targeting myostatin. In conclusion, we demonstrate that a lentiviral vector effectively performed shRNA myostatin gene knockdown and gene delivery into in vitro produced bovine embryos. Thus, this technique can be considered a novel option for the production of transgenic embryos and double muscle mass animals.

Dressing liposomal particles with chitosan and poly(vinylic alcohol) for oral vaccine delivery

Liposomes have been used as adjuvants since 1974. One major limitation for the use of liposomes in oral vaccines is the lipid structure instability caused by enzyme activities. Our aim was to combine liposomes that could encapsulate antigens (i.e., Dtxd, diphtheria toxoid) with chitosan, which protects the particles and promotes mucoadhesibility. We employed physical techniques to understand the process by which liposomes (SPC: Cho, 3: 1) can be sandwiched with chitosan (Chi) and stabilized by PVA (poly-vinylic alcohol), which are biodegradable, biocompatible polymers. Round, smooth-surfaced particles of REVs-Chi (reversed-phase vesicles sandwiched by Chi) stabilized by PVA were obtained. The REVs encapsulation efficiencies (Dtxd was used as the antigen) were directly dependent on the Chi and PVA present in the formulation. Chi adsorption on the REVs surface was accompanied by an increase of zeta-potential. In contrast, PVA adsorption on the REVs-Chi surface was accompanied by a decrease of zeta-potential. The presence of Dtxd increased the Chi surface-adsorption efficiency. The PVA affinity by mucine was 2,000 times higher than that observed with Chi alone and did not depend on the molecule being in solution or adsorbed on the liposomal surface. The liberation of encapsulated Dtxd was retarded by encapsulation within REVs-Chi-PVA. These results lead us to conclude that these new, stabilized particles were able to be adsorbed by intestinal surfaces, resisted degradation, and controlled antigen release. Therefore, REVs-Chi-PVA particles can be used as an oral delivery adjuvant.

Kvinnlig Könsstympning : Litteraturstudie om praktisk handläggning och komplikationsrisker vid förlossning

Today around 28 000 women originally from countries where FGM is practised, are living in Sweden. Many of them are at childbearing age which means that knowledge about FGM and its consequences is of outmost importance during delivery. The aim of this study is to describe current research on how to manage the delivery, regarding deinfibulation and the following stitching as well as the risk of complications when the labouring woman is mutilated. This review of literature is based on 12 scientific articles published between years 1989 – 2005. Five different databases have been searched with use of a large number of keywords.The review found that no scientific research has been carried out that describes how deinfibulation and following stitching should be managed when the woman is mutilated. All available articles within this area are referring to best practice only. The review also found that the conclusions of the studies are contradictory. The majority, however, show an increased frequency for prolonged labour that could be related to FGM. The three largest studies also show an increased rate of caesarean section among mutilated women. In the few studies that examine haemorrhage, the majorities show an increased tendency to bleed, that could be related to FGM. Several articles emphasize the importance of good routines for deinfibulation to reduce the risk for complications.In summary it can be established that due to methodological problems in many studies, no reliable conclusion can be made that the researched complications exists to a greater extent when the woman is mutilated

Production and Delivery (Optimization of production system and reliability)

This thesis is done to solve two issues for Sayid Paper Mill Ltd Pakistan. Section one deals with a practical problem arise in SPM that is cutting a given set of raw paper rolls of known length and width, and a set of product paper rolls of known length (equal to the length of raw paper rolls) and width, practical cutting constraints on a single cutting machine, according to demand orders for all customers. To solve this problem requires to determine an optimal cutting schedule to maximize the overall cutting process profitability while satisfying all demands and cutting constraints. The aim of this part of thesis is to develop a mathematical model which solves this problem.Second section deals with a problem of delivering final product from warehouse to different destinations by finding shortest paths. It is an operational routing problem to decide the daily routes for sending trucks to different destination to deliver their final product. This industrial problem is difficult and includes aspect such as delivery to a single destination and multiple destinations with limited resources. The aim of this part of thesis is to develop a process which helps finding shortest path.

Amningsduration vid sectio och vaginalförlossning : Breastfeeding duration at cesarean section and vaginal delivery. Apopulationbased register study.

Bakgrund: Amning är av stor betydelse för det nyfödda barnet och mamma, både ur närings- och trygghetsaspekter. Tidigare studier om sambandet mellan förlossningssätt och amning visar motstridiga resultat; vissa studier indikerar att sectio påverkar amningen negativt medan andra studier inte visar på något samband.Syftet: Att undersöka huruvida det finns demografiska och hälsorelaterade skillnader hos mammor gällande förlossningssätt samt om förlossningssätt påverkar amningsdurationen upp till två månaders ålder.Metod: Studien har en populationsbaserad kohortdesign och omfattar n= 35250 mamma-barn par i Örebro- och Uppsala län, där barnet fötts åren 1993-2001. Statistiska analyser har genomförts med Chi-square test, binär logistisk regressionsanalys och multivariat logistik regressionsanalys.Resultat: Visade att mammor som förlösts med sectio ammade i lägre utsträckning vid två månaders ålder i jämförelse med mammor som förlösts vaginalt. Många riskfaktorer identifierades för en ökad risk att förlösas med sectio: län, hälsofaktorer hos mamma och barn, paritet, mammans ålder, rökning samt socioekonomiska faktorer. Resultatet kan hjälpa barnmorskan i hennes profession, genom att kunskap erhålls om dessa samband. Barnmorskan kan därmed identifiera riskfaktorer, arbeta förebyggande och underlätta initieringen av amning.Konklusion: Barnmorskor kan med hjälp av denna studie öka medvetenheten hos vårdpersonal angående sectioförlösta mammors behov av extra stöd vid initiering av amning.

Maternal health care professionals perspective on the provision and use of antenatal and delivery care : a qualitative descriptive study in rural Vietnam

Background. High quality maternal health care is an important tool to reduce maternal and neonatal mortality. Services offered should be evidence based and adapted to the local setting. This qualitative descriptive study explored the perspectives and experiences of midwives, assistant physicians and medical doctors on the content and quality of maternal health care in rural Vietnam. Method. The study was performed in a rural district in northern Vietnam. Four focus group discussions with health care professionals at primary health care level were conducted. The data was analysed using qualitative manifest and latent content analysis. Result. Two main themes emerged: "Contextual conditions for maternal health care" and "Balancing between possibilities and constraints". Contextual conditions influenced both pregnant women's use of maternal health care and health care professionals' performance. The study participants stated that women's uses of maternal health care were influenced by economical constraints and cultural norms that impeded their autonomy in relation to childbearing. Structural constraints within the health care system included inadequate financing of the primary health care, resulting in lack of human resources, professional re-training and adequate equipment. Conclusion. Contextual conditions strongly influenced the performance and interaction between pregnant women and health care professionals within antenatal care and delivery care in a rural district of Vietnam. Although Vietnam is performing comparatively well in terms of low maternal and child mortality figures, this study revealed midwives' and other health care professionals' perceived difficulties in their daily work. It seemed maternal health care was under-resourced in terms of staff, equipment and continuing education activities. The cultural setting in Vietnam constituting a strong patriarchal society and prevailing Confucian norms limits women's autonomy and reduce their possibility to make independent decisions about their own reproductive health. This issue should be further addressed by policy-makers. Strategies to reduce inequities in maternal health care for pregnant women are needed. The quality of client-provider interaction and management of pregnancy may be strengthened by education, human resources, re-training and provision of essential equipment.