Phonophoresis and topical drug delivery

In this study, investigations into phonophoresis were conducted by employing 3 distinct in vitro models. The aim of the first model was to evaluate the effect of ultrasound on the migration rate of different classes of molecules through agar gel. The derived data suggested that small, relatively hydrophobic molecules are more susceptible to ultrasound-enhanced diffusion through the water-filled channels of the agar gel. The application of heat alone increased drug migration by a similar magnitude as the ultrasound, indicating that ultrasonic heating directly increases the thermodynamic potential for diffusion. In the second experimental system, whole rat skin was pre-sonicated and then examined for changes in its barrier properties. At high intensities (1 to 2W cm-2), ultrasonic waves irreversibly compromised the barrier properties of the skin, following the general patterns described in the literature reports. At low intensities (< 1W cm-2), ultrasound discharged sebum from the sebaceous glands so as to fill much of the hair follicle shafts. This entirely novel phenomenon is probably produced by the mechanical effects of the beam. The deposition of sebaceous lipids within the hair follicle shafts can mean that this absorption pathway is blocked for hydrophilic molecules that penetrate via this route. Consequently, this phenomenon can be utilised as a probe to measure the relative follicular contribution to total penetration for these molecules. In the final phonophoresis model, modified Franz cells were employed in order to assess the ultrasound effect on the concurrent transdermal permeation of various molecules through whole rat skin. For the most lipophilic agent tested, the rate-limiting step of absorption was partitioning from the stratum corneum into the viable epidermis. Sonication did not accelerate this step.

Pre-conception care : current practice and methods of provision

This thesis examines the present provisions for pre-conception care and the views of the providers of services. Pre-conception care is seen by some clinicians and health educators as a means of making any necessary changes in life style, corrections to imbalances in the nutritional status of the prospective mother (and father) and the assessment of any medical problems, thus maximizing the likelihood of the normal development of the baby. Pre-conception care may be described as a service to bridge the gap between the family planning clinic and the first ante-natal booking appointment. There were three separate foci for the empirical research - the Foresight organisation (a charity which has pioneered pre-conception care in Britain); the pre-conception care clinic at the West London Hospital, Hammersmith; and the West Midlands Regional Health Authority. The six main sources of data were: twenty five clinicians operating Foresight pre-conception clinics, couples attending pre-conception clinics, committee members of the Foresight organisation, staff of the West London Hospital pre-conception clinic, Hammersmith, District Health Education Officers working in the West Midlands Regional Health Authority and the members of the Ante-Natal Care Action Group, a sub-group of the Regional Health Advisory Group on Health Promotion and Preventive Medicine. A range of research methods were adopted. These were as follows: questionnaires and report forms used in co-operation with the Foresight clinicians, interviews, participant observation discussions and informal meetings and, finally, literature and official documentation. The research findings illustrated that pre-conception care services provided at the predominantly private Foresight clinics were of a rather `ad hoc' nature. The type of provision varied considerably and clearly reflected the views held by its providers. The protocol which had been developed to assist in the standardization of results was not followed by the clinicians. The pre-conception service provided at the West London Hospital shared some similarities in its approach with the Foresight provision; a major difference was that it did not advocate the use of routine hair trace metal analysis. Interviews with District Health Education Officers and with members of the Ante Natal Care Action Group revealed a tentative and cautious approach to pre-conception care generally and to the Foresight approach in particular. The thesis concludes with a consideration of the future of pre-conception care and the prospects for the establishment of a comprehensive pre-conception care service.

Transglutaminases:nature's biological glues

Transglutaminases (Tgases) are a widely distributed group of enzymes that catalyse the post-translational modification of proteins by the formation of isopeptide bonds. This occurs either through protein cross-linking via epsilon-(gamma-glutamyl)lysine bonds or through incorporation of primary amines at selected peptide-bound glutamine residues. The cross-linked products, often of high molecular mass, are highly resistant to mechanical challenge and proteolytic degradation, and their accumulation is found in a number of tissues and processes where such properties are important, including skin, hair, blood clotting and wound healing. However, deregulation of enzyme activity generally associated with major disruptions in cellular homoeostatic mechanisms has resulted in these enzymes contributing to a number of human diseases, including chronic neurodegeneration, neoplastic diseases, autoimmune diseases, diseases involving progressive tissue fibrosis and diseases related to the epidermis of the skin. In the present review we detail the structural and regulatory features important in mammalian Tgases, with particular focus on the ubiquitous type 2 tissue enzyme. Physiological roles and substrates are discussed with a view to increasing and understanding the pathogenesis of the diseases associated with transglutaminases. Moreover the ability of these enzymes to modify proteins and act as biological glues has not gone unnoticed by the commercial sector. As a consequence, we have included some of the present and future biotechnological applications of this increasingly important group of enzymes.

Enhanced information transmission with signal-dependent noise in an array of nonlinear elements

We have investigated information transmission in an array of threshold units that have signal-dependent noise and a common input signal. We demonstrate a phenomenon similar to stochastic resonance and suprathreshold stochastic resonance with additive noise and show that information transmission can be enhanced by a nonzero level of noise. By comparing system performance to one with additive noise we also demonstrate that the information transmission of weak signals is significantly better with signal-dependent noise. Indeed, information rates are not compromised even for arbitrary small input signals. Furthermore, by an appropriate selection of parameters, we observe that the information can be made to be (almost) independent of the level of the noise, thus providing a robust method of transmitting information in the presence of noise. These result could imply that the ability of hair cells to code and transmit sensory information in biological sensory systems is not limited by the level of signal-dependent noise. © 2007 The American Physical Society.

Failing to meet expectations:the meaning of intimate partner violence for Pakistanis

Background: Intimate Partner Violence (IPV) is a major social and public health problem affecting people across cultures, religions and societies. Much research has been undertaken to offer understanding and explanations of this phenomenon, its determinants, and its consequences in developed countries around the world. However, there is still a paucity of research on IPV in many areas of the developing world such as Pakistan. Although various studies have been conducted to demonstrate the prevalence of IPV in the country, none of the studies have tried to explore the meaning of IPV from the perspective of Pakistani people. Aim: This study aimed to explore understandings of Pakistani men and women of IPV. It aimed to develop a theory to explain the meaning of IPV and the process through which it occurs, from the perspective of Pakistani people. Methods: The study utilised a qualitative approach with constructivist grounded theory methods and analysis techniques. Data was collected from Karachi, Pakistan and Sheffield, UK. Forty one people (20 from Pakistan and 21 from UK) participated in the study. Findings: The participants identified IPV as a serious concern. Although verbal abuse is often included in definitions of IPV, the participants did not consider shouting, raising the voice or scolding as a type of violence. Hitting, beating, pushing, throwing objects, and pulling hair were identified as acts of physical violence, and non-consensual sex was identified as a form of sexual abuse. Participants identified failure to meet role expectations of a husband or wife as a key contributor to the development of conflict between partners which could lead to IPV. Examples of various expectations from a wife include completing household chores, looking after husband, looking after children, looking after in laws, respecting and adjusting to in-law's customs and traditions. Important expectation from a husband include provision of finances, acting as a bridge, maintaining a balance between his wife and other family members particularly his mother and sisters, and taking the responsibility for his wife and children. Failure to meet these expectations could contribute to conflict and subsequent violence. This appeared to be shaped by cultural issues such as common use of arranged marriages, the rarity of divorce and the centrality of the extended family to the intimate partnership. Implications: Any interventions aimed at reducing IPV in Pakistani people must consider the meaning and causes of IPV from the perspective of that group.

Association of SNPs in LCP1 and CTIF with hearing in 11 year old children:findings from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort and the G-EAR consortium

BACKGROUND: The genetic basis of hearing loss in humans is relatively poorly understood. In recent years, experimental approaches including laboratory studies of early onset hearing loss in inbred mouse strains, or proteomic analyses of hair cells or hair bundles, have suggested new candidate molecules involved in hearing function. However, the relevance of these genes/gene products to hearing function in humans remains unknown. We investigated whether single nucleotide polymorphisms (SNPs) in the human orthologues of genes of interest arising from the above-mentioned studies correlate with hearing function in children. METHODS: 577 SNPs from 13 genes were each analysed by linear regression against averaged high (3, 4 and 8 kHz) or low frequency (0.5, 1 and 2 kHz) audiometry data from 4970 children in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth-cohort at age eleven years. Genes found to contain SNPs with low p-values were then investigated in 3417 adults in the G-EAR study of hearing. RESULTS: Genotypic data were available in ALSPAC for a total of 577 SNPs from 13 genes of interest. Two SNPs approached sample-wide significance (pre-specified at p = 0.00014): rs12959910 in CBP80/20-dependent translation initiation factor (CTIF) for averaged high frequency hearing (p = 0.00079, β = 0.61 dB per minor allele); and rs10492452 in L-plastin (LCP1) for averaged low frequency hearing (p = 0.00056, β = 0.45 dB). For low frequencies, rs9567638 in LCP1 also enhanced hearing in females (p = 0.0011, β = -1.76 dB; males p = 0.23, β = 0.61 dB, likelihood-ratio test p = 0.006). SNPs in LCP1 and CTIF were then examined against low and high frequency hearing data for adults in G-EAR. Although the ALSPAC results were not replicated, a SNP in LCP1, rs17601960, is in strong LD with rs9967638, and was associated with enhanced low frequency hearing in adult females in G-EAR (p = 0.00084). CONCLUSIONS: There was evidence to suggest that multiple SNPs in CTIF may contribute a small detrimental effect to hearing, and that a sex-specific locus in LCP1 is protective of hearing. No individual SNPs reached sample-wide significance in both ALSPAC and G-EAR. This is the first report of a possible association between LCP1 and hearing function.