Biliary atresia (BA), the most common cause of pediatric liver transplantation, remains a challenge for clinicians and investigators. Patient survival and QOL have been greatly improved by liver transplantation compared to the time when hepatoportoenterostomy, or Kasai operation is the only treatment. However, organ transplantation has intrinsic demerits, such as donor shortage and chronic rejection. To develop new therapeutic options, the greater understanding of its pathogenesis is indispensable. The etiology of BA is still unclear, although there is some evidence for viral, toxic,and multiple genetic factors. The fact that the pathology of BA proceeds during a period of biliary growth and remodeling suggests an involvement of developmental anomalies. Recent studies indicate the association of the etiology of BA with some gene functions such as laterality genes,epigenetics regulation and/or miRNAs function. In this review, we present a perspective of advances in the understanding of the disease focusing on bile duct developmental anomaly.

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Microsurgery has been introduced into the various fields of clinical surgical treatment. This high level of surgical skills requires an adequate training. International Society for ExperimentalMicrosurgery(ISEM)founded by Sun Lee from 1991 covers both this technique and various knowledge of physiology, immunology, pharmacology, and tissue engineering. The Japan Society for Organ Preservation and Medical Biology(JSOPMB)is also established for horizontal research for many scientists. In this review article, I introduced experimental microsurgery as a translational research skill from the key point of both societies.

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Mammalians circadian pacemaker resides in the paired suprachiasmatic nuclei (SCN) and influences a multitude of biological processes, including the sleep-wake rhythm. Clock genes are the genes that control the circadian rhythms in physiology and behavior. 24 hr rhythm is demonstrated for the function of physiology and the pathophysiology of diseases. The effectiveness and toxicity of many drugs vary depending on dosing time. Such chronopharmacological phenomena are influenced by not only the pharmacodynamics but also pharmacokinetics of medications. Chronotherapy is especially relevant, when the risk and/or intensity of the symptoms of disease vary predictably over time as exemplified by allergic rhinitis, arthritis, asthma, myocardial infarction, congestive heart failure, stroke, and peptic ulcer disease. However, the drugs for several disease are still given without regard to the time of day. The monitoring of rhythm, overcome of rhythm disruption and manipulation of rhythm from viewpoints of molecular clock are essential to improved progress and diffusion of chronopharmacotherapy. From viewpoints of pharmaceutics, the application of biological rhythm to pharmacotherapy may be accomplished by the appropriate timing of conventionally formulated tabletes and capsules, and the special drug delivery system to synchronize drug concentrations to rhythms in disease activity. Therefore, we introduce an overview of the dosing time-dependent alterations in therapeutic outcome and safety of drug. The underlying mechanisms and usefulness are introduced from viewpoint of chronopharmaology and chronotherapy.

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While careful consideration to avoid a second scourge like thalidomide is required, disadvantages for mothers and fetuses by restraint of necessary drug prescription because of too much concern about the effects on fetuses must be avoided. Information sources to evaluate teratogenicity of drugs themselves include epidemiological investigations, case reports, and animal reproduction studies and are considered more reliable in this order. And breast milk is the best source of nutrition and it also serves as a source of substances providing immunity for a newborn infant. However, there are times when nursing mothers may have to take some kind of medication, so it is necessary to evaluate the effect of drugs that are transferred to infants through breast milk, and to select medications with minimal adverse effects.

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Pancreatic islet transplantation is a promising option for the treatment of type 1 diabetic patients that experience hypoglycemic unawareness despite maximal care. After the successful demonstration of the Edmonton protocol, more than 600 patients with type 1 diabetes in more than 50 institutions have received islet transplantation to treat their disease. Islet transplantation has advanced significantly on several fronts, including pancreatic ductal protection, improved pancreas preservation systems, a new islet purification method, and culture/preservation of isolated islets. These techniques are now used for clinical islet transplantation. Our method makes it feasible to use these pancreata efficiently for islet transplantation in patients with type 1 diabetes.

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Recent advances in obstetric ultrasoundhave stimulatedinnovative interventions in fetal surgery. Myelomeningocele (MMC) is a promising target lesion in this fieldbecause in many cases, the defect is not structurally complicated, andusually, there are no associations with other serious disorders, including genetic abnormalities. Therefore, prenatal surgical repair of MMC is likely to lead to life-long improvements in terms of postnatal quality of life. However, since a fetus is not a small infant from the pathophysiological viewpoint, the most appropriate surgical procedure would not be a conventional one that has been employedd uring the postnatal periodin the past. In this report, we attempted to cover the defect experimentally using a collagen sheet made of highly dense type-I collagen fibrils (collagen vitrigel membrane). We hope to prevent the development of encephalomyelopathly before birth by protecting the exposed spinal cord from intrauterine chemical and/or mechanical damages causedby persistent contact with the amniotic fluidand /or inside uterine tissues andblocking cerebrospinal fluidloss through the open neural tube, thus ameliorating the Chiari II malformation. In our in vitro study, the heat-adhesive collagen membrane could be attached accurately onto the target animal tissue by laser light irradiation. Furthermore, there was increased attachment of the membrane with the combineduse of photopolymerizing chitosan as an additional adhesive. Considering all the results, it seemedprobable that both of these modalities were feasible for endoscopic surgery. Histological examination showedthat there was inward growth of the 2 predominant dermal cellular components-fibroblasts andkeratinocytes-into the collagen vitrigel membrane. In conclusion, collagen vitrigel membrane can effectively seal a skin defect based on a non-suturing mode of action. This membrane is a promising material for future endoscopic repair of fetal MMC.

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