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PubMed2003

CREB, memory enhancement and the treatment of memory disorders: promises, pitfalls and prospects.

The treatment of memory disorders, such as the gradual weakening of memory with age, the ravages of Alzheimer's disease and the cognitive deficits in various forms of mental retardation, may greatly benefit from a better understanding of the molecular and cellular mechanisms of memory formation. There is increasing interest in the possibility of pharmacologically enhancing learning and memory even in the absence of specific anatomically evident pathology. Substantial evidence in experimental systems ranging from molluscs to humans indicates that the cAMP response element binding protein (CREB) is a core component of the molecular switch that converts short- to long-term memory. Recent studies have greatly strengthened and refined our understanding of the role of CREB in learning and memory in mammals, in addition to providing greater insight into the molecular mechanisms of CREB regulation and function. This involvement of CREB and the upstream signalling pathways leading to its activation in learning-associated plasticity makes them attractive targets for drugs aimed at improving memory function, in both diseased and healthy individuals. However, CREB and its close relatives cAMP response element modulator and activating transcription factor-1 are ubiquitous proteins with several critical functions. This creates hurdles that the authors believe may limit the usefulness of CREB per se as a target for the development of memory-enhancing drugs, and focus on components of the upstream signalling pathways or on specific downstream targets will be required.

Amino Acid Sequence↗
PubMed2002

Clinical gene therapy - first international conference. 24-26 January 2002, Groningen, the Netherlands.

The first International Conference on Clinical Gene Therapy focused primarily on gene therapy for cardiovascular disorders, genetic diseases (hemophilia, cystic fibrosis) and cancer, with particular emphasis on clinical trials and advanced preclinical studies. Recent improvements in vector technologies led to the first demonstration that gene therapy could cure a disease in a clinically relevant animal model of hemophilia. This significant progress at the preclinical level, using both viral and non-viral vectors, paved the way for phase I clinical trials in patients suffering from hemophilia A. The first report on hemophilia A gene therapy using a non-viral ex vivo approach was encouraging and revealed modest improvements in clinical endpoints. The status of clinical gene therapy for the treatment of peripheral limb and myocardial ischemia by therapeutic angiogenesis was highlighted as showing an apparent increase in collateral development and reduced limb or myocardial ischemia in some patients. Gene therapy for cystic fibrosis turned out to be a much tougher nut to crack than initially assumed, and the hopes for, and hurdles faced by, gene therapy approaches for this disease were discussed. Phase III clinical trials using retroviral-based suicide gene therapy for cancer revealed no significant therapeutic benefit in patients suffering from glioblastoma multiforme. Nevertheless, new and promising approaches for cancer gene therapy are being developed that rely on the use of targetable vectors and conditionally replicating vectors that replicate specifically in cancer cells; this may overcome some of the bottlenecks of cancer gene therapy by improving therapeutic efficacy. Although few diseases have been treated effectively by gene therapy so far, the stage appears set for new and significant advances in clinical trials.

Journal Article↗
PubMed2004

Immunogenicity of polyepitope libraries assembled by epitope shuffling: an approach to the development of chimeric gene vaccination against malaria.

Developing a polyepitope vaccine which contains diverse antigenic types is a promising strategy to cope with the problem of malaria variation and diversity. However, arranging the peptides to produce the most effective immunogenicity remains a hurdle. In an attempt to develop an effective complex antigenic gene vaccine, we constructed a polyepitope library by randomly assembling epitopes using the epitope shuffling technique. The polyepitope library, which contains epitopes from different antigens of Plasmodium falciparum, was divided into five sub-libraries based on the size of chimeric genes. Here we report that higher antibody titers were observed in mice with immunized with sub-libraries containing genes >1200 bp, using enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence (IFAT) assay to determine both individual epitope peptides and the natural parasites at the erythrocyte stage. Different levels of IgG subtypes and cytokines were elicited by different sub-library and administration times. In a rodent malaria model, some groups of immunized mice were partially cross-protected against a lethal challenge from Plasmodium yoelii. These results suggest that the immunogenicity of a polyepitope chimeric antigen is essentially conformation- and length-dependent, and demonstrates that the promising advantage of epitope shuffling technology is that it allows us to randomly assemble many polyepitope molecules in tandem format. This finding also indicates that polyepitope library vaccination is a suitable approach for screening optimized chimeric gene vaccines against malaria and other diseases.

Animals↗
PubMed2006

Targeted gene repair: the ups and downs of a promising gene therapy approach.

As a novel form of molecular medicine based on direct actions over the genes, targeted gene repair has raised consideration recently above classical gene therapy strategies based on genetic augmentation or complementation. Targeted gene repair relies on the local induction of the cell's endogenous DNA repair mechanisms to attain a therapeutic gene conversion event within the genome of the diseased cell. Successful repair has been achieved both in vitro and in vivo with a variety of corrective molecules ranging from oligonucleotides (chimeraplasts, modified single-stranded oligonucleotides, triplex-forming oligonucleotides), to small DNA fragments (small fragment homologous replacement (SFHR)), and even viral vectors (AAV-based). However, controversy on the consistency and lack of reproducibility of early experiments regarding frequencies and persistence of targeted gene repair, particularly for chimeraplasty, has flecked the field. Nevertheless, several hurdles such as inefficient nuclear uptake of the corrective molecules, and misleading assessment of targeted repair frequencies have been identified and are being addressed. One of the key bottlenecks for exploiting the overall potential of the different targeted gene repair modalities is the lack of a detailed knowledge of their mechanisms of action at the molecular level. Several studies are now focusing on the assessment of the specific repair pathway(s) involved (homologous recombination, mismatch repair, etc.), devising additional strategies to increase their activity (using chemotherapeutic drugs, chimeric nucleases, etc.), and assessing the influence of the cell cycle in the regulation of the repair process. Until therapeutic correction frequencies for single gene disorders are reached both in cellular and animal models, precision and undesired side effects of this promising gene therapy approach will not be thoroughly evaluated.

Animals↗
PubMed2004

Methods for improved hemorrhage control.

Trauma is the leading cause of death from age 1 to 34 years and is the fifth leading cause of death overall in the USA, with uncontrolled hemorrhage being the leading cause of potentially preventable death. Improving our ability to control hemorrhage may represent the next major hurdle in reducing trauma mortality. New techniques, devices, and drugs for hemorrhage control are being developed and applied across the continuum of trauma care: prehospital, emergency room, and operative and postoperative critical care. This brief review focuses on drugs directed at life-threatening hemorrhage. The most important of these new drugs are injectable hemostatics, fibrin foams, and dressings. The available animal studies are encouraging and human studies are required.

Adolescent↗
PubMed2026

Harnessing Probiotic LAB and Bacteriocins for Clean-Label Food Processing and Biopreservation: Omics, Molecular Innovations and Industrial Applications.

The persistence of microbial agents in foods, especially spore forming bacteria is one of the most significant challenges to food preservation and safety, undermining product quality, shelf life, and consumer health. The use of traditional control methods, including thermal processing and chemical preservatives, are increasingly limited by consumer demands for minimally processed foods, and the emergence of resistant microbial strains. Advances have been made in the use of probiotics like lactic acid bacteria (LAB) and their biometabolites like bacteriocins in food processing and preservation, particularly to control biofilm and endospore forming pathogens including Bacillus sp., Listeria sp., Staphylococcus sp., Clostridium sp., E. coli etc. in foods and food processing plants/surfaces. Given the ability of these organisms to cause foodborne illness and form resilient biofilms in the food processing ecosystem and their resistance to the conventional method of their elimination, the antimicrobial peptides (bacteriocins) are gaining increasing prominence as useful alternatives to synthetic antimicrobials in enhancing food safety and combating the threats of these pathogens. This review addresses current information on the inhibition of persistent microbial spoilage contaminants, biofilm-forming pathogens, and spore formers of interest to the food industry using LAB and their bacteriocins. Current developments in isolation, characterization, and mode of action of bacteriocins are explored, including synergistic activity with other preservative hurdle techniques such as encapsulation, and nanobiotechnology. Importantly, there is a focus on the utilization of molecular and omics-based approaches to enable a better understanding of bacteriocin biosynthesis, gene regulation, host-microbe interactions and gut microbiome regulation potential of probiotic LABs, permitting the rational development of targeted and strain-specific interventions. Developments in the incorporation of bacteriocin-producing LAB into functional starter cultures and bio-protective products, and challenges in stability, regulatory approval, and scalability for industrial use, are also discussed in the paper. Despite their considerable potential, broader translation remains constrained by regulatory requirements, production and formulation costs, variable efficacy in complex food matrices, and the limited validation of many candidate bacteriocins beyond laboratory and model-food systems. Collectively, these advances position LAB and their bacteriocins at the leading edge of developing sustainable, clean-label, and efficacious functional foods and food preservation systems. Their functionality can be expanded by integrating genomics, synthetic biology, and predictive modeling for the maximization of their biopreservative potential in diverse food matrices and in gut microbiota modulation.

Bioactive Peptides↗
PubMedDate not supplied

Development and application of adenoviral vectors for gene therapy of cancer.

For successful gene vaccination and therapy of cancer, it is essential to develop gene delivery vectors that can meet clinical and social requirements. The need for improved vectors was clearly manifested during the peak of the first wave of gene therapy. Adenoviral (Ad) vectors have recently drawn the attention of many of those involved in the field of gene therapy for cancer because of their practical advantages and application potential. Many experiments, innovations, preclinical studies, and clinical trials have generated an overwhelming amount of data and literature concerning this vector system. It is hoped that the comprehensive review presented here, which includes the principles, potential, capacity, and limitations of the current Ad systems, will help to further the rational development of the system. The literature in this article is organized in an attempt to emphasize Ad vector development in the aspects of technical approaches, practical hurdles and strategies to overcome them, significant experimental results, recent advances, future directions, etc. The technical range of this review covers details that are intended to serve as a reference for advanced technical readers and provide a foundation for initiates in the field of Ad vector gene therapy. The material presented here is also intended for nontechnical persons who want to have an overview of the significance and potential of the technology.

Adenoviridae↗
PubMedDate not supplied

Apical sodium dependent bile acid transporter (ASBT, SLC10A2): a potential prodrug target.

A major hurdle impeding the successful clinical development of drug candidates can be poor intestinal permeability. Low intestinal permeability may be enhanced by a prodrug approach targeting membrane transporters in the small intestine. Transporter specificity, affinity, and capacity are three factors in targeted prodrug design. The human apical sodium dependent bile acid transporter (SLC10A2) belongs to the solute carrier family (SLC) of transporters and is an important carrier protein expressed in the small intestine. In spite of its appearing to be an excellent target for prodrug design, few studies have targeted human apical sodium dependent bile acid transporter (hASBT) to improve oral bioavailability. This review discusses bile acids including their chemistry and their absorptive disposition. Additionally, hASBT-mediated prodrug targeting is discussed, including QSAR, in vitro models for hASBT assay, and the current progress in utilizing hASBT as a drug delivery target.

Administration, Oral↗
PubMed2003

Alginate microcapsules for pancreatic islet cell graft immunoprotection: struggle and progress towards the final cure for type 1 diabetes mellitus.

Lights and shadows have been associated with the use of alginate/polyaminoacidic microcapsules for transplantation of pancreatic islet cells for the therapy of diabetes mellitus, with no recipient pharmacological immunosuppression. In fact, preliminary success in rodents has generally not matched the results achieved in diabetic higher mammals. The restricted availability of cadaveric human donor organs/tissue, coupled to regulatory hurdles in the use of microcapsules in patients, has significantly delayed the progress of microencapsulated islet grafts into pilot clinical trials. While the basic formulation of microcapsules from the author's laboratory, originally comprised of an alginate gel (AG) core, a double poly-L-ornithine (PLO) coat and an outer AG coat, has virtually remained unchanged, highly purified 'clinical grade' AG has been introduced in order to try to surmount regulatory restrictions. In parallel, novel insulin-producing cell types have been employed to fill the capsules, with particular regard to non-human tissue, such as adult and, more recently, neonatal porcine islets. In particular, using neonatal porcine islets enveloped in AG-PLO microcapsules, hyperglycaemia has been corrected in several diabetic animal models. Should standardisation and optimisation problems associated with both AG procurement and other membrane physical-chemical fabrication parameters be surmounted, microcapsules containing either human or, possibly, pig islets, could be close to approval for Phase I human clinical trials.

Alginates↗
PubMed2004

Predicting respiratory motion for four-dimensional radiotherapy.

Adapting radiation delivery to respiratory motion is made possible through corrective action based on real-time feedback of target position during respiration. The advantage of this approach lies with its ability to allow tighter margins around the target while simultaneously following its motion. A significant hurdle to the successful implementation of real-time target-tracking-based radiation delivery is the existence of a finite time delay between the acquisition of target position and the mechanical response of the system to the change in position. Target motion during the time delay leads to a resultant lag in the system's response to a change in tumor position. Predicting target position in advance is one approach to ensure accurate delivery. The aim of this manuscript is to estimate the predictive ability of sinusoidal and adaptive filter-based prediction algorithms on multiple sessions of patient respiratory patterns. Respiratory motion information was obtained from recordings of diaphragm motion for five patients over 60 sessions. A prediction algorithm that employed both prediction models-the sinusoidal model and the adaptive filter model-was developed to estimate prediction accuracy over all the sessions. For each session, prediction error was computed for several time instants (response time) in the future (0-1.8 seconds at 0.2-second intervals), based on position data collected over several signal-history lengths (1-7 seconds at 1-second intervals). Based on patient data included in this study, the following observations are made. Qualitative comparison of predicted and actual position indicated a progressive increase in prediction error with an increase in response time. A signal-history length of 5 seconds was found to be the optimal signal history length for prediction using the sinusoidal model for all breathing training modalities. In terms of overall error in predicting respiratory motion, the adaptive filter model performed better than the sinusoidal model. With the adaptive filter, average prediction errors of less than 0.2 cm (1sigma) are possible for response times less than 0.4 seconds. In comparing prediction error with system latency error (no prediction), the adaptive filter model exhibited lesser prediction errors as compared to the sinusoidal model, especially for longer response time values (>0.4 seconds). At smaller response time values (<0.4 seconds), improvements in prediction error reduction are required for both predictive models in order to maximize gains in position accuracy due to prediction. Respiratory motion patterns are inherently complex in nature. While linear prediction-based prediction models perform satisfactorily for shorter response times, their prediction accuracy significantly deteriorates for longer response times. Successful implementation of real-time target-tracking-based radiotherapy requires response times less than 0.4 seconds or improved prediction algorithms.

Algorithms↗
PubMed2026

The Long Road to Long-Acting: What Oral PrEP and CAB-LA Teach Us About Scaling Lenacapavir.

Despite significant biomedical advances, human immunodeficiency virus (HIV) remains a persistent global health crisis, with over 40 million people affected as of 2023, two-thirds of whom live in the World Health Organization (WHO) African Region. However, from an HIV prevention perspective, the more urgent concern is the continued occurrence of approximately 1.3 million new infections annually, particularly in sub-Saharan Africa and in settings where incidence is stable or increasing. This commentary explores the evolving landscape of HIV prevention, focusing on the trajectory of oral pre-exposure prophylaxis (PrEP), long-acting injectable cabotegravir (CAB-LA), and the newly emerging lenacapavir. While oral PrEP opened new possibilities, adherence challenges have limited its impact. CAB-LA demonstrated superior efficacy but encountered access, cost, and delivery barriers that restricted uptake. Lenacapavir, offering 6-monthly subcutaneous dosing with &#x2265;&#xa0;99.9% efficacy in trials, holds the potential to overcome these hurdles. As of May 2026, lenacapavir had received regulatory approval in 17 countries, including several African nations, while regulatory reviews remained ongoing in multiple additional countries, reflecting the rapid global expansion of access to this long-acting HIV prevention option. However, its success depends on clinical promise, timely licensing, affordability, and integration into health systems. Drawing from real-world lessons of oral PrEP and CAB-LA, this paper argues that a proactive, coordinated rollout of lenacapavir could dramatically expand prevention reach. With global stakeholders aiming for 3 million users by 2028 and strategic licensing in 120 countries, the groundwork is in place. The recent release of WHO guidance recommending lenacapavir as an additional PrEP option further strengthens this momentum. Yet, equitable delivery, user-centred models, and strong policy backing will be critical. Ultimately, long-acting PrEP is not just a clinical breakthrough; it is a test of health systems' ability to deliver innovation at scale.

Humans↗
PubMed2001

A new integrated program for natural product development and the value of an ethnomedical approach.

There is a need for less expensive alternative therapies, especially in the treatment of chronic illnesses. This presentation addresses the issues inherent in the use of natural products in a drug-discovery or development program and reviews a model program developed by the U.S. National Institutes of Health (NIH) and administered by the Fogarty International Center at the NIH. Eighty percent (80%) of the world's population relies on medicinal plants for their primary health care. The World Health Organization has been promoting traditional medicine as a source of less expensive, comprehensive medical care, especially in developing countries. Natural products have also been successful in drug development. Over 50% of the best-selling pharmaceuticals in use today are derived from natural products. In a natural-product drug development program, it is the diversity of the natural products that is especially interesting. Thanks to technologic advances, now is a good time to be looking for new drugs in the natural-product arena. But there are major hurdles to overcome in a natural-products development program, namely, time-to-lead, supply, and ownership. Time-to-lead is complex because most natural products are mixtures or crude extracts. It can be very difficult to isolate the active principles and elucidate their structures. The difficulty of obtaining sufficient supply is often given as a reason for not becoming involved in natural-product drug development or discovery. This presentation details some ways these seeming hurdles can be overcome. The concept of ownership has changed dramatically in recent years. Until recently, genetic resources were considered to belong to no one and to therefore be the heritage of everyone. The United Nations Convention on Biodiversity and the meetings in Rio de Janeiro in 1992, redefined biodiversity ownership. Genetic biodiversity has a potential value and belongs to the country of origin. The International Conservation of Biodiversity Groups (ICBGs) was founded in 1992 to address such issues. This presentation discusses the importance of integrating efforts in conservation, economic development, and drug development into one program. The presentation details a collaboration that includes an ICBG based at the Walter Reed Army Institute of Research and its four partner organizations and discusses the associated programs the collaboration has underway.

Bioethics↗
PubMed2003

Is training in psychosocial interventions worthwhile? Report of a psychosocial intervention trainee follow-up study.

A follow-up study of psychosocial intervention (PSI) trainees from the Sheffield and Maudsley training centres was undertaken in three stages. In Stage 1, 141 students, at two PSI training centres, were sent a simple postal questionnaire to elicit career trajectory following PSI training. A response rate of 82% was achieved. The sub-group, who had been trained and who still engaged in clinical practice were identified and followed-up in more detail (n=96). The effect of PSI training in a range of domains was investigated. The impact of training may not be to equip students with formal technical skills in CBT and family work. What is more likely is that trainees acquired proficiency in: working effectively using a case management model; conveying 'therapeutic optimism'; enabling users to meet their own goals and helping them to develop better coping strategies; using 'stress vulnerability' and formal outcome measures as means of structuring this approach. The secondary aim of the study was to identify and prioritise the barriers that impede the effective implementation of PSI skills in routine service settings. For the second phase of the survey the response rate was again 82%. This group's service managers were identified and surveyed for the same information and 59% responded. The aim was to gather information about implementation issues from both the clinical and service perspectives. The results of the survey indicate that PSI training has a positive impact on the development of services for people with serious mental health problems although there are serious organisational hurdles for managers, trainees and organisations to overcome if PSI skills are to be properly implemented. Key factors that impact upon faithful implementation are related to resource issues (caseload size), organisational factors (the existence of an implementation plan and training strategy), and the extent to which the trainee's team is supportive.

Adult↗
PubMed1998

Sample pooling to expedite bioanalysis and pharmacokinetic research.

In the progression from drug discovery to development, not only pharmacokinetic (PK) characterization needed for lead compound selection often becomes a rate-limiting step, but also high volume of routine sample analysis ensued from numerous required biodisposition studies for the lead compounds and their back-ups often place a burdensome hurdle to the throughput of IND and NDA development phases. Higher throughput of PK screening via cocktail dosing has been reported to accelerate PK screening in the discovery phase. However, concerns on drug-drug interactions and other limitations associated with the cocktail M-in-One dosing (multiple compounds per dose per animal) has prompted the present investigation of sample pooling alongside One-in-One dosing strategy (one compound per dose per animal) as an alternative to the cocktail dosing approach. Using traditional HPLC for bioanalysis as an example, the present study illustrate the concept and usefulness of sample pooling that could facilitate the throughput of PK screening and characterization in both discovery and development phases. Six proprietary dopamine D4 receptor antagonist preleads representing three different chemical classes, used as model compounds (C1-C6), were administered orally to rats. One rat received one compound and three rats were used for each compound. Six unknown plasma samples from six different rats at each time point were pooled. The pooled plasma samples were extracted by a one-step liquid-liquid extraction and concentrations of the six preleads were quantitated simultaneously. By sample pooling, a substantial amount of PK information was obtained at the same time for the six preleads, which requires much less workload than when bioanalysis is dealt with one compound at a time. For the first time in one aspect of innovative bioanalysis, the present investigation has demonstrated that sample pooling following One-in-One dosing can be utilized to enhance the throughput rate in PK screening in discovery phase. The sample pooling approach is likely to be useful in enhancing the throughput of PK characterization in development phase. With the advent of LC-MS and its becoming user-friendly, where separation of drug compounds is no longer an issue, the uniqueness of sample pooling may also pose a new way of thinking in regard to the old ways of handling bioanalysis for traditional PK research.

Animals↗
PubMed2026

What influenced the use of embedded genetic expertise by non-genetic clinicians: a qualitative study using the diffusion of innovations theory and theoretical domains framework.

BACKGROUND: While employing change agents is a widely used strategy to support implementation of evidence-based practices in healthcare, the perspectives of the target users of this intervention are under-explored. Within a genomic care setting in Australia, we examined non-genetic clinicians' views of and experience with embedded genetic counsellors employed as external change agents to support the adoption of genomics in clinical care. METHODS: We conducted qualitative interviews with 16 non-genetic healthcare professionals involved in different models of genomic care, all of which employed genetic counsellors as external change agents to provide embedded genetic expertise and support in non-genetic specialty clinics. The Diffusion of Innovations (DOI) theory and the Theoretical Domains Framework (TDF) were drawn upon to guide the study design and data analysis to explore the enablers/barriers to non-genetic clinicians' use of genetic expertise and the wider implementation context of the change agent approach. RESULTS: The TDF domain 'Belief about Consequences' was a positive influence on non-genetic specialists' view of the embedded change agents, when they believed that the change agents positively impacted patient outcomes and the clinicians' knowledge and practice of using genomics in routine care. Meanwhile, major barriers were related to 'Environmental Context & Resources,' e.g. time constraints and logistic hurdles of involving change agents. Perceived attributes related to 'complexity' and 'observability' of genetic expertise were critical factors influencing the decision to put the support to actual use, impacting the diffusion of the genomic innovation. CONCLUSIONS: Our study offers insights into behavioural influences and contextual conditions shaping clinicians' decisions to interact with genetic counsellor change agents and incorporate (or not) their expertise into their routine care. Such understandings can inform future design and implementation of interventions that use change agents to support the adoption of innovations, such as genomics, effectively and sustainably.

Journal Article↗
PubMed2005

Original approach to the individual characteristics associated with forgone healthcare: a study in underprivileged areas, Paris region, France, 2001-2003.

BACKGROUND: The social inequalities in health have endured or even worsened comparatively throughout different social groups since the 1990s. Our objective was to identify the individual characteristics (socio-economic status, living conditions, individuals' social integration, health beliefs, expectations and representation and psychological characteristics) statistically associated with the fact of stating (or not) that healthcare had been forgone because of cost. METHODS: In this cross-sectional, multi-centre study we randomly selected a study sample from five underprivileged areas in the Paris region. A multiple logistic regression model was used to calculate the odds ratios (OR) and 95% confidence interval (CI). The validity of the model was assessed by goodness-of-fit tests (Pearson and deviance) and by the study of 100 bootstrap samples. RESULTS: After making adjustments for numerous individual socio-economic and health characteristics, we observed a higher occurrence of reported forgone healthcare among people who have had financial worries during adulthood [ORyes/no=5.47 (1.44-20.75)], a life-course experience of physical, sexual or psychological abuse [ORyes/no=2.86 (1.40-5.84)]; who have experienced childhood difficulties [OR1/never difficulties=5.28 (1.81-15.39), OR2-4/never=7.62 (2.69-21.57), OR>4/never=8.57 (2.39-30.80)]; who have expressed a low degree of sickness orientation [OR(low/high)=2.62 (1.33-5.14)], a high worry/concern about health [ORhigh/low=2.71 (1.33-5.50)] and a low self-esteem [ORmedium/high=8.28 (1.44-47.64), ORlow/high=16.44 (2.81-96.24)]. CONCLUSION: Aside from purely financial hurdles, other factors play a role in the non-use of healthcare services. Health policies mainly promoting equal financial access to healthcare have little chance of abating health inequalities.

Adolescent↗
PubMed2001

Cell signalling - the proteomics of it all.

A challenge for biomedical scientists today is to arrive at an understanding of cellular behavior on a global scale. The advent of DNA microarrays has greatly facilitated discovery of gene expression profiles associated with different cellular states. The problem of understanding cellular signaling at the level of the interacting proteins is in some ways more challenging. Ashman et al. discuss the current methods available for studying protein interactions on a global scale, as well as directions for the future. Technical hurdles exist at many stages, from the isolation of protein complexes, to the determination of their composition, to the software and databases needed to analyze the results of large-scale, high-throughput datasets. Ashman et al. suggest that, with advances in technology and cooperation among academia and industry, a global protein interaction map that underlies cellular behavior will emerge as an essential resource for basic and applied research.

Computational Biology↗
PubMedDate not supplied

Hepatocyte transplantation: state of the art and strategies for overcoming existing hurdles.

Over three decades of research in experimental animals and several clinical trials have brought us to the threshold of hepatocyte transplantation for the treatment of acute and chronic liver failure, and inherited metabolic disorders. However, more extensive clinical studies and routine clinical application are hampered by the shortage of good quality of donor cells. To overcome these hurdles, current research has focused on the search for alternatives to adult primary hepatocytes, such as liver cell progenitors, fetal hepatoblasts, embryonic, bone marrow or umbilical cord blood stem cells and conditionally immortalized hepatocytes. Cross-species hepatocyte transplantation is also being explored. It is hoped that ongoing research will permit the application of hepatocyte transplantation to the treatment of a wide array of liver diseases.

Animals↗