Development of ropivacaine hydrochloride-loaded dissolving microneedles as a local anesthetic agent: A proof-of-concept.

Ropivacaine hydrochloride (RPL) is a local anesthetic agent that has been widely used for the treatment of pain during or after surgery. However, this drug is only available in parenteral dosage form and may contribute to the infiltration of RPL into the plasma, causing some undesirable side effects. Intradermal delivery of RPL using dissolving microneedles may become a promising strategy to deliver such drugs into the skin. This research aimed to develop RPL-loaded dissolving microneedles (DMN-RPLs) as a proof of the concept of intradermal delivery of a local anesthetic. The DMN-RPLs were fabricated using either centrifugation or air-pressurized chamber methods. Several polymers, such as poly(vinyl pyrrolidone) (PVP), poly(vinyl alcohol) (PVA), and sodium hyaluronate (SH), were utilized for manufacturing the DMN-RPLs. The prepared DMN-RPLs were assessed for their thermal properties, chemical bonds, mechanical strength, insertion ability, skin-dissolution study, and drug content. Furthermore, in-skin deposition and dermatokinetic studies were also performed. The results showed that F9 (30 % w/w PVP-4 % w/w SH) and F10 (30 % w/w PVP-5 % w/w PVA) containing 5 % w/w of RPL were the most promising formulations, as shown by their needle height reduction (<10 %) and insertion depth (∼400 µm). Both formulations were also able to deliver more than 60 % of the RPL contained in the DMNs into the epidermis, dermis, and receiver compartment. This study, for the first time, has provided a proof concept to deliver RPL as a local anesthetic using DMNs and the intradermal route, aiming to minimize pain and discomfort during administration and improve the patient's experience.

A Study of the Discussions on Psychiatry of Korea in the 1960s and 1970s* - From Mental Hygiene to Modern Psychiatry.

This study is to review the emergence of new psychiatrists, scientific rationalization, and popular internalization to reorganize the formation process of modern psychological medicine system. Unlike eugenic psychiatry from the Japanese Colonial Era, the social conditions and contexts forming autonomous system of psychiatry of Korea in the 1960s and 1970s have been concentrated. The discussion approach has been tried to secure two perspectives-treatment and criticism-at the same time and to expand the time and scope of study through the extensive texts such as newspapers, magazines, books, advertisements, and others in the 1960s and 1970s. Through formation of subject, rationalization, and popularization, this study has surveyed the characteristics of psychiatry in the 1960s and 1970s to accentuate complicated conditions and kinetic steps to systemize psychiatry as scientific field to promote treatment of patients by deviating from mental hygiene approaching national mental health from cleanliness and removal. The characteristics are summarized as follows. First, as the ethical models of good doctors, medical paternalistic doctors, and non-authoritarian symmetric doctors have been proposed as good psychiatrists by new medical specialists with experience of globality, a new subject emerges. However, there has been illegalization process of unlicensed medical practitioner excluded by the regulatory authority called "clearness." Second, the rationalization of psychiatry has been accelerated through the dispute of enactment of Mental Hygiene Law, segmentalization of concept of mental illness, and scientific characteristics. Especially, the disputes over enactment of Mental Hygiene Law focused on criminalization of mental patients brought a result to regulate the patients as the target of humanistic treatment and potential criminals at the same time. Third, popularization of psychiatry has embraced invisible mental illness into popular daily life through visual measure called medicine advertisement, and through the discussion about social neurosis, a new paradigm for diagnosis of Korean society has been proposed. Moreover, by focusing on autobiographical works with voices of patients, this article reveals a new doctor-patient relationship.

Altered microRNA regulation in Huntington's disease models.

Huntington's disease (HD) is a genetic neurodegenerative disease caused by abnormal CAG expansion. MicroRNAs (miRNAs) are short RNA molecules regulating gene expression, and are implicated in a variety of diseases including HD. However, the profiles and regulation of miRNAs in HD are not fully understood. Here, we analyzed the miRNA expression and miRNA regulators in two transgenic models of HD, YAC128 and R6/2 mice, and in a 3-nitropropionic acid (3NP)-induced striatal degeneration rat model. After characterizing the phenotypes by behavioral tests and histological analyses, we profiled striatal miRNAs using a miRNA microarray and we measured the key molecules involved in miRNA biogenesis and function. YAC128 mice showed upregulation-dominant miRNA expressions at 5 months and downregulation-dominant expressions at 12 months. Concomitantly, the expressions of Drosha-DGCR8, Exportin-5, and Dcp1 were increased at 5months, and the expression of Dicer was decreased at 12 months. In 10-week-old R6/2 mice, downregulation was dominant in the miRNA expressions and the level of Drosha decreased concomitantly. Nine miRNAs (miR-22, miR-29c, miR-128, miR-132, miR-138, miR-218, miR-222, miR-344, and miR-674*) were commonly down-regulated in both the 12-month-old YAC128 and 10-week-old R6/2 mice. Meanwhile, 3NP rats showed dynamic changes in the miRNA profiles during disease development and a few miRNAs with altered expression. Our results show that transgenic HD mice have abnormal miRNA biogenesis. This information should aid in future studies on therapeutic application of miRNAs in HD.