Current Online-pharmacy-dictionary- News Results

Non-prescription medicines: current issues in Australian community pharmacy.

Int J Pharm Pract. 2009 Aug; 17(4): 207-13
Tan AC, Emmerton L

OBJECTIVES: This qualitative research aimed to improve understanding of the perceptions, experiences and attitudes of community pharmacists regarding developments in the nonprescription medicines market. METHOD: Qualitative data were collected via in-depth interviews with 20 community pharmacists in Brisbane, Australia. Pharmacists-in-charge were randomly telephoned from a list generated from online pharmacy-locator services and invited to participate in a face-to-face semi-structured interview based on six themes. The data collected were transcribed verbatim and analysed for prominent themes, major issues, differences and unique individual responses. KEY FINDINGS The topic commonly of concern to participants was the descheduling of non-prescription medicines (including ibuprofen and nicotine-replacement therapy) for availability via non-pharmacy medicine retailers. Other key findings and common themes related to the current scheduling of non-prescription medicines as Pharmacist Only Medicines and Pharmacy Medicines (largely favoured), the importance of pharmacists' advice on non-prescription medicines and the online system for control of pseudoephedrine sales (Project STOP; widely commended). CONCLUSIONS: Despite some variability in opinions and the potential for professionally desirable responses, the findings generally supported professional initiatives to preserve non-prescription medicines as a domain of community pharmacies. The involvement of pharmacists in medicine sales was largely favoured as an opportunity to maintain control over supply and to advise on appropriate medicines usage. These data may inform the quality supply of non-prescription medicines, and are of significance to countries operating or debating similar scheduling systems for non-prescription medicines.

Midpregnancy cordocentesis experience by maternal fetal medicine fellows.

Ultrasound Obstet Gynecol. 2010 Mar 9;
Tongprasert F, Srisupundit K, Luewan S, Phadungkiatwattana P, Pranpanus S, Tongsong T

OBJECTIVE:: To describe the experience of systematic cordocentesis training among maternal fetal medicine (MFM) fellows MATERIALS AND METHODS:: MFM fellows who had completed systematic model training were recruited to perform mid-pregnancy cordocentesis under supervision. The details of the procedures were prospectively recorded. The exclusion criteria were: 1) multiple pregnancies; 2) fetal chromosomal abnormalities; and 3) fetal structural anomalies. The outcome measures included success rate, duration of the procedures, fetal loss and complications. RESULTS:: Five MFM fellows were recruited to perform 1,116 mid-pregnancy diagnostic cordocenteses: an average of 223 procedures, range 185-259, per fellow over a period of two years. Of these, 184 were excluded because of fetal abnormalities; the remaining 932 were available for analysis. Cordocentesis was performed on free-floating umbilical cord (79.3%) and at the placental insertion site (20.7%). The immediate complication of transient fetal bradycardia was found in 10% of cases. The success rate was as high as 98.1-100%, whereas the fetal loss rate was 1.3%. Mean+/-SD duration of the successful procedures was 4.4+/-4.7 minutes (range of average time 3.7-5.9 minutes). CONCLUSION:: MFM fellows with systematic training were able to perform cordocentesis with very high success rates, and with an acceptable procedure-related fetal loss rate. An intensive course of preclinical training with the model, and more than 60 procedures on actual patients under supervision may probably be recommended. Copyright (c) 2010 ISUOG. Published by John Wiley & Sons, Ltd.

Delta2D and Proteomweaver: Performance evaluation of two different approaches for 2-DE analysis.

Electrophoresis. 2010 Mar 9;
Millioni R, Miuzzo M, Sbrignadello S, Murphy E, Puricelli L, Tura A, Bertacco E, Rattazzi M, Iori E, Tessari P

2-DE is a fundamental technology used in proteomics research. However, despite its high capacity to simultaneously separate several proteins for subsequent identification and quantitative comparison studies, a drawback for this technique is its limited reproducibility, especially when comparing data from different laboratories. 2-DE-related variability can be broadly divided into two categories: experimental and post-experimental. Experimental variability depends on physical and chemical parameters, whereas post-experimental variability arises when gels are analyzed by different software packages, particularly when different workflows are followed. In this paper, we compared the analysis performance of two software packages, Delta2D and Proteomweaver, using both standard and experimental gel images. Using standard gel images, the false negative spot count was 50% lower, the false positive count was 77% lower, the true positive count was 19% higher and spot matching was 4% higher in Delta2D when compared to Proteomeweaver. Using experimental gel images, we found that the total amount of time taken to complete the analysis with Delta2D was 30% that of the time needed with Proteomweaver and required fewer user interventions. The differences between ease of use and workflow strategy of these programs is discussed.

Antiapoptotic effects of anthocyanins on rotator cuff tenofibroblasts.

J Orthop Res. 2010 Mar 9;
Park HB, Hah YS, Yang JW, Nam JB, Cho SH, Jeong ST

Degeneration of the rotator cuff tendon, which involves apoptosis of the tenofibroblasts, is one of the most common shoulder problems that can lead eventually to a full-thickness rotator cuff tendon tear. The current authors evaluated both the ability of anthocyanins, which are powerful antioxidants, to reduce apoptosis in oxidation-stressed rotator cuff tenofibroblasts, and the molecular mechanism for this antiapoptotic action. Anthocyanins demonstrated a dose-dependent ability to inhibit H(2)O(2)-induced apoptosis in cultured tenofibroblasts, as assessed by MTT assay and FACS analysis. H(2)O(2) increased the phosphorylation of extracellular regulated kinase1/2 (ERK1/2) and of c-Jun N-terminal kinase (JNK) and the production of reactive oxygen species (ROS). In contrast, treatment with anthocyanins decreased this activation of ERK1/2 and JNK, as confirmed by Western blot analysis, and reduced the production of ROS, as verified by fluorescent microscopic and FACS analyses. These findings suggest that anthocyanins, by suppressing JNK, ERK1/2, and intracellular ROS production, have a concentration-dependent antiapoptotic effect on rotator cuff tenofibroblasts exposed to an oxidative stressor, and may have therapeutic potential. (c) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Multiple functionalities of polyelectrolyte multilayer films: new biomedical applications.

Adv Mater. 2010 Jan 26; 22(4): 441-67
Boudou T, Crouzier T, Ren K, Blin G, Picart C

The design of advanced functional materials with nanometer- and micrometer-scale control over their properties is of considerable interest for both fundamental and applied studies because of the many potential applications for these materials in the fields of biomedical materials, tissue engineering, and regenerative medicine. The layer-by-layer deposition technique introduced in the early 1990s by Decher, Moehwald, and Lvov is a versatile technique, which has attracted an increasing number of researchers in recent years due to its wide range of advantages for biomedical applications: ease of preparation under "mild" conditions compatible with physiological media, capability of incorporating bioactive molecules, extra-cellular matrix components and biopolymers in the films, tunable mechanical properties, and spatio-temporal control over film organization. The last few years have seen a significant increase in reports exploring the possibilities offered by diffusing molecules into films to control their internal structures or design "reservoirs," as well as control their mechanical properties. Such properties, associated with the chemical properties of films, are particularly important for designing biomedical devices that contain bioactive molecules. In this review, we highlight recent work on designing and controlling film properties at the nanometer and micrometer scales with a view to developing new biomaterial coatings, tissue engineered constructs that could mimic in vivo cellular microenvironments, and stem cell "niches."

Advances in biomimetic and nanostructured biohybrid materials.

Adv Mater. 2010 Jan 19; 22(3): 323-36
Ruiz-Hitzky E, Darder M, Aranda P, Ariga K

The rapid increase of interest in the field of biohybrid and biomimetic materials that exhibit improved structural and functional properties is attracting more and more researchers from life science, materials science, and nanoscience. Concomitant results offer valuable opportunities for applications that involve disciplines dealing with engineering, biotechnology, medicine and pharmacy, agriculture, nanotechnology, and others. In the current contribution we collect recent illustrative examples of assemblies between materials of biological origin and inorganic solids of different characteristics (texture, structure, and particle size). We introduce here a general overview on strategies for the preparation and conformation of biohybrids, the synergistic effects that determine the final properties of these materials, and their diverse applications, which cover areas as different as tissue engineering, drug delivery systems, biosensing devices, biocatalysis, green nanocomposites, etc.

Dendritic polyglycerols for biomedical applications.

Adv Mater. 2010 Jan 12; 22(2): 190-218
Calderón M, Quadir MA, Sharma SK, Haag R

The application of nanotechnology in medicine and pharmaceuticals is a rapidly advancing field that is quickly gaining acceptance and recognition as an independent area of research called "nanomedicine". Urgent needs in this field, however, are biocompatible and bioactive materials for antifouling surfaces and nanoparticles for drug delivery. Therefore, extensive attention has been given to the design and development of new macromolecular structures. Among the various polymeric architectures, dendritic ("treelike") polymers have experienced an exponential development due to their highly branched, multifunctional, and well-defined structures. This Review describes the diverse syntheses and biomedical applications of dendritic polyglycerols (PGs). These polymers exhibit good chemical stability and inertness under biological conditions and are highly biocompatible. Oligoglycerols and their fatty acid esters are FDA-approved and are already being used in a variety of consumer applications, e.g., cosmetics and toiletries, food industries, cleaning and softening agents, pharmaceuticals, polymers and polymer additives, printing photographing materials, and electronics. Herein, we present the current status of dendritic PGs as functional dendritic architectures with particular focus on their application in nanomedicine, in drug, dye, and gene delivery, as well as in regenerative medicine in the form of non-fouling surfaces and matrix materials.

Protective Effect of Labisia pumila on Stress-Induced Behavioral, Biochemical, and Immunological Alterations.

Planta Med. 2010 Mar 9;
Kour K, Sharma N, Chandan BK, Koul S, Sangwan PL, Bani S

The aim of the present study was to investigate the antistress potential of LABISIA PUMILA aqueous extract (LPPM/A003) using a battery of tests widely employed in different stressful situations. Pretreatment of experimental animals with LPPM/A003 caused an increase in the swimming endurance and hypoxia time and also showed the recovery of physical stress-induced depletion of neuromuscular coordination and scopolamine induced memory deficit. LPPM/A003 at graded doses reversed the chronic restraint stress (RST), induced depletion of CD4 (+) and CD8 (+) T lymphocytes, NK cell population, and corresponding cytokines expression besides downregulating the stress-induced increase in plasma corticosterone, a major stress hormone. In addition, LPPM/A003 reversed the chronic stress-induced increase in adrenal gland weight, serum alanine aminotransferase (ALT), alkaline phosphatase (ALP), and hepatic lipid peroxidation (LP) levels and augmented the RST induced decrease in hepatic glutathione (GSH), thymus and spleen weight. Thus, we conclude that LPPM/A003 has the ability to reverse the alterations produced by various stressful stimuli and therefore restores homeostasis.

Reduced Availability of Potential Cornea Donors: Reasons and Suggestions.

Klin Monbl Augenheilkd. 2010 Mar 9;
Rosenbaum K, Rottler J, Steinbach R, Huber KK

AIM: The purpose of the study was to analyse the number of potential cornea donors in relationship to the number of actual donors. Furthermore, the reasons for the discrepancy between the number of the potential and actual donors were analysed. METHODS: Over a period of 6 months data were collected from 6 hospitals and the institute for forensic medicine of the university hospital. The reasons why only a few actual donors from a big pool of potential donors remain for transplantation were investigated. RESULTS: Circumstances related to the medical staff were causal for refusal in 37 % of the cases. In 23 % the cause for refusal was related to the relatives (23 %). Furthermore, in 16 organisational problems caused a failure in cornea donation. 18 % were excluded due to contraindications. A total rate of 6 % actual donors was achieved. CONCLUSIONS: The final consent rate was only 6 % out of all potential donors. Organisational failure was only 16 % in contrast to 60 % refusal due to causes relating to medical staff and relatives. Therefore, further education of physicians and the public is needed.

Liposomal Doxorubicin and nab-Paclitaxel: Nanoparticle Cancer Chemotherapy in Current Clinical Use.

Methods Mol Biol. 2010; 624: 385-92
Gaitanis A, Staal S

Liposomal doxorubicin and nab-paclitaxel are nanoparticle formulations of traditional cancer chemotherapy drugs which have ample clinical experience both pre- and post-nanoparticle modification. The alterations in pharmacokinetics, pharmacodynamics, efficacy, and toxicity compared with their parent compounds are instructive for future development of nanoparticle-based therapies. In this article we review the current status of these agents, emphasizing the alterations in clinical behavior resulting from the nanoparticle formulation of the parent compound.

Use of tissue microarray to facilitate oncology research.

Methods Mol Biol. 2010; 632: 239-50
Gouveris P, Weinberger PM, Psyrri A

HPV-positive oropharyngeal squamous cell carcinomas (OSCC) represent a distinct disease entity from traditional OSCC. We hypothesized that for HPV DNA-positive cases, p16 expression status differentiates the biologically relevant ones.We determined HPV16DNA viral load in a cohort of 79 oropharyngeal squamous cell cancers by real-time polymerase chain reaction (PCR). We used cervical cancer as a disease model for HPV-initiated epithelial cancer. In cervical cancer, p53 and Rb expression is reduced, while p16 expression is increased. We used TMA technology to facilitate interrogation of this cohort for p53, Rb, and p16 protein expression using a quantitative, in situ method of protein analysis (AQUA analysis). Our results indeed delineate three biologically and clinically distinct types of oropharyngeal squamous cell cancers based on HPV-DNA determination and p16 expression status: one class of HPV-negative/p16-nonexpressing (HPV-negative), one class of HPV-positive/p16-nonexpressing (HPV-inactive), and one class of HPV positive/p16-expressing (HPV-active) oropharyngeal tumors. We demonstrated that only the HPV-active tumors share a similar molecular phenotype to cervical cancers, and are the ones associated with favorable prognosis.

DMET Microarray Technology for Pharmacogenomics-Based Personalized Medicine.

Methods Mol Biol. 2010; 632: 99-124
Burmester JK, Sedova M, Shapero MH, Mansfield E

Human genome sequence variation in the form of single nucleotide polymorphisms (SNPs) as well as more complex structural variation such as insertions, duplications, and deletions underlies each individual's response to drugs and thus the likelihood of experiencing an adverse drug reaction. The ongoing challenge of the field of pharmacogenetics is to further understand the relationship between genetic variation and differential drug responses, with the overarching goal being that this will lead to improvements in both the safety and efficacy of drugs. The Affymetrix((R)) DMET Plus Premier Pack (DMET stands for Drug Metabolizing Enzymes and Transporters) enables highly multiplexed genotyping of known polymorphisms in Absorption, Distribution, Metabolism, and Elimination (ADME)-related genes on a single array. The DMET Plus Panel interrogates markers in 225 genes that have documented functional significance in phase I and phase II drug metabolism enzymes as well as drug transporters. The power of the DMET Assay has previously been demonstrated with regard to several different drugs including warfarin and clopidogrel. In a research study using an earlier four-color version of the assay, it was demonstrated that warfarin dosing can be influenced by a cytochrome P450 (CYP) 4F2 variant. Additionally, the assay has been used to demonstrate that CYP2C19 variants with decreased enzyme activity led to lower levels of the active clopidogrel metabolite, resulting in a decreased inhibition of platelets and a higher rate of cardiovascular events when compared to noncarriers of the DNA variant. Thus, highly multiplexed SNP genotyping focused on ADME-related polymorphisms should enable research into development of safer drugs with greater efficacy.

Isolation of total RNA from transgenic mouse melanoma subsets using fluorescence-activated cell sorting.

Methods Mol Biol. 2010; 632: 27-44
Tighe S, Held MA

The majority of tumors, including melanoma, are phenotypically heterogeneous in that they contain various cell populations with differential expression of cell surface antigens such as CD133/Prominin-1. We have used fluorescence-activated cell sorting (FACS) technology to purify CD133(+) and CD133(-) cellular subsets from mouse melanoma models for high-quality total RNA practical for downstream applications such as expression profiling. Implementation of this strategy can lead to higher resolution of transcripts that are potentially important for the survival and functionality of one cancer cell population relative to another. Suboptimal extraction of RNA after FACS is common and can ultimately result in misinterpretations that impede the effective design of novel therapies. Here, we describe a number of methods that have been amenable to the successful isolation of high-quality total RNA after FACS of CD133(+) and CD133(-) mouse melanoma cell fractions.

Direct Application of siRNA for In Vivo Pain Research.

Methods Mol Biol. 2010; 623: 383-95
Sarret P, Doré-Savard L, Beaudet N

Pain is the new burden of the twenty-first century, raising enormous socio-economic costs to developed and underdeveloped countries. Chronic pain is a central nervous system (CNS) pathology, affecting a large proportion of the population. Morphine and its derivatives are still the golden clinical standards for treating pain although they induce severe side effects. To this day, we still have poor understanding of nociceptive pain and its underlying complex mechanisms; furthermore, novelty in clinical analgesics is lacking.RNA interference technologies are promising both for pain research and treatment. This genetic approach will likely provide new insights into pain mechanisms and eventually offer nonpharmacological therapeutic approaches. In vivo research is thus crucial to reach this goal. Preclinical studies on rodents are necessary to validate small interfering RNA (siRNA) candidates and to target precise physiological pain modulators. Aiming treatment at the CNS is delicate work, and here we will describe how to perform adequate pain research using siRNA, including siRNA preparation and injection, animal behavioral models, and CNS tissue collection.

Inhibitory RNA molecules in immunotherapy for cancer.

Methods Mol Biol. 2010; 623: 325-39
Mao CP, Wu TC

Over the past few decades, our expanding knowledge of the mammalian immune system - how it is developed, activated, and regulated - has fostered hope that it may be harnessed in the future to successfully treat human cancer. The immune system activated by cancer vaccines may have the unique ability to selectively eradicate tumor cells at multiple sites in the body without inflicting damage on normal tissue. However, progress in the development of cancer vaccines that effectively capitalize on this ability has been limited and slow. The immune system is restrained by complex, negative feedback mechanisms that evolved to protect the host against autoimmunity and may also prevent antitumor immunity. In addition, tumor cells exploit a plethora of strategies to evade detection and elimination by the immune system. For these reasons, the field of cancer immunotherapy has suffered considerable setbacks in the past and faces great challenges at the present time. Some of these challenges may be overcome through the use of RNA interference, a process by which gene expression can be efficiently and specifically "knocked down" in cells. This chapter focuses on the current status and future prospects in the application of small interfering RNA and microRNA, two main forms of RNA interference, to treat cancer by curtailing mechanisms that attenuate the host immune response.

A new approach for therapeutic use by RNA interference in the brain.

Methods Mol Biol. 2010; 623: 313-24
Akaneya Y

RNA interference (RNAi) is a gene silencing phenomenon that is induced by ribonucleoprotein complexes containing 21-28 nucleotides (nt) of double-stranded RNA (si/miRNA). Although this phenomenon occurs in an inherent manner, it can also be induced in an artificially manipulated manner. Recently, the understanding of RNAi mechanisms has progressed from that in plants to that in mammals. As RNAi is a highly efficient and readily available procedure to knockdown specific targets, it can possibly be used as a new technique providing many researchers and clinicians with opportunities for its experimental use and prospective clinical application. Consequently, there has been a rush of elucidation of the effective sequences of siRNAs used for the knockdown of the targets in many fields, including neuroscience and experiments for neurological disorders. However, in many cases, it is difficult to effectively introduce si/miRNA into cells without causing injury to the recipient cells. Apart from the off-target effects and the pathogenic property of si/miRNA per se, which are designed and produced, the possibility and intensity of cell injury by RNAi depends on the method employed for the introduction of si/miRNA. Possible methods include si/miRNA delivery systems using liposome, polyethylenimine (PEI), electroporation, and viral infection. Currently, various methods for delivering si/miRNA into cells have been developed and challenged. Here, I review the advantages, disadvantages, and perspective of employing the RNAi procedure in the brain. Given that the disadvantages of RNAi can be overcome, the clinical application of RNAi technologies may be useful in realizing the elimination of pathogenic genes not only in the brain, but also in the other organs in the near future.

Polyethylenimine (PEI)/siRNA-Mediated Gene Knockdown In Vitro and In Vivo.

Methods Mol Biol. 2010; 623: 283-97
Höbel S, Aigner A

Since its discovery about 10 years ago, RNA interference (RNAi) has become an almost standard method for the knockdown of any target gene of interest. It is mediated by small interfering RNAs (siRNAs), which trigger a catalytic mechanism for mRNA degradation. Consequently, the delivery of intact siRNA is of critical importance for the induction of RNAi. Due to the physicochemical and biological properties of siRNAs, resulting in high instability and poor cellular uptake, siRNA modifications and pharmaceutical formulations have been used to enhance RNAi efficacy. This is particularly relevant for the in vivo delivery of siRNAs, which still poses a major hurdle for the experimental or therapeutic application of RNAi.Polyethylenimines (PEIs) are water-soluble, linear, or branched synthetic polymers of variable length with protonable amino groups in every third position. We have shown that certain PEIs are able to form noncovalent complexes with siRNAs, which mediate their protection against nucleolytic degradation as well as enhance their cellular uptake and intracellular release. In this chapter, the preparation and use of PEI/siRNA complexes for various in vitro and in vivo applications are described. Examples for conducting gene targeting experiments and the analysis of knockdown efficacies are given.

Nonviral siRNA Delivery for Gene Silencing in Neurodegenerative Diseases.

Methods Mol Biol. 2010; 623: 211-29
Prakash S, Malhotra M, Rengaswamy V

Linking genes with the underlying mechanisms of diseases is one of the biggest challenges of genomics-driven drug discovery research. Designing an inhibitor for any neurodegenerative disease that effectively halts the pathogenicity of the disease is yet to be achieved. The challenge lies in crossing the blood-brain barrier (BBB)/blood-cerebrospinal fluid barrier (BCSFB) to reach the catalytic pockets of the enzyme/protein involved in the molecular mechanism of the disease process. Designing siRNA with exquisite specificity may result in selective suppression of the disease-linked gene. Although siRNA is the most promising method, it loses its potency in downregulating the gene due to its inherent instability, off-target effects, and lack of on-target effective delivery systems. Viral as well as nonviral delivery methods have been effectively tested in vivo for silencing of molecular targets and have resulted in significant efficacy in animal models of Alzheimer's disease, amyotrophic lateral sclerosis (ALS), anxiety, depression, encephalitis, glioblastoma, Huntington's disease, neuropathic pain, and spinocerebellar ataxia. To realize the full therapeutic potential of siRNA for neurodegenerative diseases, we need to overcome many hurdles and challenges such as selecting suitable tissue-specific delivery vectors, minimizing the off-target effects, and achieving distribution in sufficient concentrations at the target tissue without any side effects. Cationic nanoparticle-mediated targeted siRNA delivery for therapeutic purposes has gained considerable clinical importance as a result of its promising efficacy.

Human islet autotransplantation: the trail thus far and the highway ahead.

Adv Exp Med Biol. 2010; 654: 711-24
Hermann M, Margreiter R, Hengster P

Human islet transplantation is one of the three treatment modalities besides the daily administration of exogenous insulin and pancreas transplantation, which can be applied for the treatment of type 1 diabetic patients. Although the metabolic control achieved after islet transplantation is superior compared to exogenous insulin administration, many hurdles remain to be overcome before islet transplantation can be called a routine therapy for type 1 diabetic patients. In contrast to many other therapeutic approaches, proof of principle has been obtained for islet transplantation: As demonstrated in islet autotransplantation, the transplanted islets are not only able to survive in another organ, namely the liver, but also able to retain their functional role, in some patients even for decades. The main challenge for islet allotransplantation is, therefore, to imitate this success, thereby providing type 1 diabetic patients with a cellular therapy lasting for decades and thus circumventing the daily injections of insulin.

The Programmable Cell of Monocytic Origin (PCMO): A Potential Adult Stem/Progenitor Cell Source for the Generation of Islet Cells.

Adv Exp Med Biol. 2010; 654: 667-82
Ungefroren H, Fändrich F

Adult stem or programmable cells hold great promise in diseases in which damaged or non-functional cells need to be replaced, such as in type 1 diabetes. We have recently demonstrated that peripheral blood monocytes can be differentiated in vitro into pancreatic beta-cell-like cells capable of synthesizing insulin. The two-step phenotypic conversion commences with growth factor-induced partial reprogramming during which the cells acquire a state of plasticity along with expression of various markers of pluripotency. These cells, termed "programmable cells of monocytic origin" (PCMOs), can then be induced with appropriate differentiation media to become insulin-producing cells (NeoIslet cells). Expression profiling of transcription factors known to determine endocrine and beta-cell development in vivo indicated that NeoIslet cells resemble cells with an immature beta-cell phenotype. Current efforts focus on establishing culture conditions that (i) increase the plasticity and proliferation potential of PCMOs by enhancing the reprogramming process and (ii) improve insulin production by mimicking in vivo lineage specification and normal pancreatic endocrine development. Combining these two strategies has great potential in generating large amounts of blood-derived cells suitable for both autologous and allogeneic therapy of type 1 diabetes.