Effects of peripheral administration of rat urotensinII on circulation, and on distribution of c-Fos immunoreactive neurons in the brain

The purpose of this study was to examine the effects of intravenous injection of urotensinII on the systemic blood pressure and heart rate, and to examine whether the intraperitoneal administration of urotensinII evoked the stimulation of central neurons. Urotensin, originally isolated fish neuro-endocrine systems, is a peptide which consists of 12 amino acids. Lately human urotensinII was identified to be consisted from 11 amino acids. Receptors of urotensin have been found to highly distribute in the mammalian cadrdiovascular systems. It has been reported that urotensin evoked contraction of thoracic artery, while the dilatation of blood vessels was alternatively induced. In this study, we examined the effects of peripheral injection of rat urotensinII consisted of 14 amino acids on the circulation and on the activity of neurons in the brain. It was found that intravenous injection of rat urotensinII elicited dose-dependently decrease in blood pressure, and increase or decrease in heart rate. To examine whether an intraperitoneal injection of rat urotensinII induced an excitation of central neurons, we used immunohistochemical method to study the expression of c-Fos protein in neurons of the rat brain after intraperitoneal injection of rat urotensinII (test experiment). In the control experiment rat was intraperitoneally injected saline solution without rat urotensinII. It was found that intraperitoneal injection of rat urotensinII induced expression of c-Fos protein in several nuclei in the brain. These results suggested that rat urotensinII might exhibit physiological functions via central neuronal pathway as well as peripheral direct pathways

Järviseudun ammatti-instituutin opetusnavetan työohjeiden päivittäminen

Opinnäytetyöni käsittelee Järviseudun ammatti-instituutin opetusnavetan työohjeiden päivittämistä. Työohjeet olisi hyvä olla jokaisessa työpaikassa. Niistä on apua uuden työntekijän perehdyttämisessä sekä myös kauemmin poissa olleen työntekijän palatessa työpaikalle. Hyvät työohjeet tuovat työpaikalle myös taloudellista hyötyä, sillä ne vähentävät työtapaturmista johtuvia sairaslomia sekä luovat työntekijöille valmiudet tehokkaaseen työskentelyyn. Järviseudun ammatti-instituutin opetusnavetta on sekä työ- että oppimispaikka. Tämän vuoksi sinne halutaan kunnolliset ohjeet navetan töistä. Tavoitteena on saada helposti ymmärrettävät ohjeet, joita pystyvät hyödyntämään myös koulun ulkomaalaiset oppilaat. Tästä syystä ohjeissa käytetään kuvia tekstin ohella. Ohjeita tehtiin kahdenlaisia. Navetan perustöistä tehtiin yksityiskohtaiset kuvalliset ohjeet pienen tekstin kera. Nämä ohjeet perustuvat täysin navetan työskentelytapoihin, jotka valokuvattiin vaihe vaiheelta. Toiset ohjeet ovat enemmän teksti-muodossa, ja käsittelevät navetassa harvemmin tehtäviä työtehtäviä, jotka vaativat enemmän ammattiosaamista ja suomenkielentaitoa.This thesis is the made work instructions for Järviseutu Vocational Institute’s cowshed. Work instructions are very important in every workplace. They help when you teach new employee or when a former employee comes back to work from a long absence. Well-made work instructions are economically profitable, they decreases occupational accidents and helps employees to work effectively. Järviseutu Vocational Institute’s cowshed is a workplace and also place to study. That is a reason why work instructions have to be in good order. The objective was to create easily understandable instructions which foreigner students could also understand. That is the reason why photos with text were used in the work instructions. There are two kinds of instructions. One about the cowshed’s daily works with photos and a short text: these instructions are detailed and based on completely on the working habits in the cowshed; they were photographed step by step. The second instructions are about non-daily works. That require more professional abilities and Finnish language skills

Endogenous agonist–bound S1PR3 structure reveals determinants of G protein–subtype bias

脂質受容体の新たな活性化機構を解明 --脂質がまっすぐ伸びて活性化--. 京都大学プレスリリース. 2021-06-10.Sphingosine-1-phosphate (S1P) regulates numerous important physiological functions, including immune response and vascular integrity, via its cognate receptors (S1PR1 to S1PR5); however, it remains unclear how S1P activates S1PRs upon binding. Here, we determined the crystal structure of the active human S1PR3 in complex with its natural agonist S1P at 3.2-Å resolution. S1P exhibits an unbent conformation in the long tunnel, which penetrates through the receptor obliquely. Compared with the inactive S1PR1 structure, four residues surrounding the alkyl tail of S1P (the “quartet core”) exhibit orchestrating rotamer changes that accommodate the moiety, thereby inducing an active conformation. In addition, we reveal that the quartet core determines G protein selectivity of S1PR3. These results offer insight into the structural basis of activation and biased signaling in G protein–coupled receptors and will help the design of biased ligands for optimized therapeutics

Surrogate marker of schistocytes

Objectives : Hematopoietic stem cell transplantation (HSCT)-associated thrombotic microangiopathy (TA-TMA) is an important early post-treatment condition. This study evaluated the Revised %MICRO, a parameter obtained from the ADVIA 2120i automated blood cell counter, as a surrogate marker of the schistocyte ratio. We hypothesized that individual differences between the %MICRO value and schistocyte ratio would remain constant. Design and Methods: EDTA-2K-treated peripheral blood samples were collected from 19 patients who underwent allogeneic HSCT from April 2014 to September 2018. First, the baseline difference, X, was calculated using a sample from the first day after HSCT as X = %MICRO (first day) – schistocyte ratio (first day). Next, the Revised %MICRO for each subsequent day was calculated as Revised %MICRO = %MICRO – X. We evaluated correlations of the schistocyte ratio with the calculated %MICRO and Revised %MICRO and the RBC fragment, RBC distribution width, %MICRO and Revised %MICRO data obtained from the ADVIA 2120i. Results : The mean schistocyte percentage and Revised %MICRO were both 0.4% ± 0.6. RBC fragments correlated weakly with the %MICRO and schistocyte ratio, respectively (r = 0.162 and r = 0.771, respectively), whereas the Revised %MICRO correlated strongly with the schistocyte ratio (r = 0.893). Conclusion : The Revised %MICRO appears to be a good surrogate of the schistocyte ratio in a clinical setting

1-year tolvaptan efficacy in ADPKD

Autosomal dominant polycystic kidney disease (ADPKD) develops into end-stage kidney disease by 65 years of age in an estimated 45%-70% of patients. Recent trials revealed that tolvaptan inhibits disease progression both in early-stage or late-stage ADPKD ; however, stratified analysis showed a difference of favorable factors correlated with tolvaptan efficacy between early-stage and late-stage ADPKD. Thus, we examined the efficacy of tolvaptan in ADPKD with a wide range of estimated glomerular filtration rates (eGFR). We enrolled 24 patients with eGFR 35.3 (28.0-65.5) ml / min / 1.73m2 and evaluated treatment effect as ΔΔeGFR (ml / min / 1.73m2 / year) or ΔΔtotal kidney volume (TKV) (% / year) that was calculated as post-treatment annual change - pre-treatment annual change. Pre ΔeGFR was significantly low in eGFR responders, defined as ΔΔeGFR > 0 ml / min / 1.73m2 / year. In eGFR responders, pre ΔeGFR, post ΔeGFR, eGFR, TKV, and proteinuria were significantly correlated with ΔΔeGFR. In TKV responders defined as ΔΔTKV > 5 % / year, we identified hypertension history, proteinuria, TKV, and post ΔTKV as significantly correlated factors with ΔΔTKV. In conclusion, pre ΔeGFR may be a predictive factor of therapeutic efficacy on kidney function. Tolvaptan may have greater efficacy in early-stage ADPKD with rapid GFR decline or with well-controlled blood pressure

障害児通所施設における重症児の栄養アセスメントの現状

障害児通所施設における重症児の栄養アセスメントの現状を明らかにすることを目的に、全国の施設を対象に質問紙調査を行い320施設より回答を得、施設利用者の主障害が肢体不自由と知的障害で、年齢区分が幼児期と青年期である160施設の回答を分析した。その結果、青年期、幼児期ともに体重計測、喫食率の実施率は高く、体重変化率と体脂肪率の実施率は低かった。栄養評価(判定)の実施は、幼児期、青年期ともに2割と少なく、青年期はBMI、血清アルブミン、喫食率、幼児期はカウプ指数と成長曲線を評価(判定)の指標としている施設が多かったが、幼児期、青年期とも明確な基準値はなく、模索状態にあることが窺えた

Safety and Efficacy of FIT039 for Verruca Vulgaris: A Placebo-Controlled, Phase I/II Randomized Controlled Trial

TRIAL DESIGN: Human papillomavirus infection causes verruca vulgaris. CDK9 inhibitor FIT039 inhibits DNA virus proliferation in animal models. We conducted a multicenter, single-blind, placebo-controlled, randomized phase I/II clinical trial evaluating the safety and efficacy of FIT039 against verruca vulgaris. METHODS: Target lesions were treated with liquid nitrogen once, and a FIT039 patch or placebo patch was applied for 14 days. The primary endpoint was lesion disappearance. The secondary endpoints were safety and changes in dimension, cross-sectional area, and the number of petechial lesions. RESULTS: A total of 24 participants were randomly allocated to the FIT039 (n = 13, median age, 54 years) and placebo (n = 11, median age, 62 years) groups. Verruca vulgaris did not disappear. FIT039 decreased the dimension to 76% of the initial value on day 29, followed by an increase to 98% on day 57. Placebo showed a monotonic increase to 107% on day 57. Changes in the cross-sectional area and petechiae number were comparable between the groups. CONCLUSIONS: No drug-related adverse reactions occurred. FIT039 efficacy was not determined in this study

Structure of the dopamine D2 receptor in complex with the antipsychotic drug spiperone

統合失調症に関わるドパミン受容体の構造解明 --副作用を抑えた薬の迅速な探索・設計が可能に--. 京都大学プレスリリース. 2020-12-24.In addition to the serotonin 5-HT2A receptor (5-HT2AR), the dopamine D2 receptor (D2R) is a key therapeutic target of antipsychotics for the treatment of schizophrenia. The inactive state structures of D2R have been described in complex with the inverse agonists risperidone (D2Rris) and haloperidol (D2Rhal). Here we describe the structure of human D2R in complex with spiperone (D2Rspi). In D2Rspi, the conformation of the extracellular loop (ECL) 2, which composes the ligand-binding pocket, was substantially different from those in D2Rris and D2Rhal, demonstrating that ECL2 in D2R is highly dynamic. Moreover, D2Rspi exhibited an extended binding pocket to accommodate spiperone’s phenyl ring, which probably contributes to the selectivity of spiperone to D2R and 5-HT2AR. Together with D2Rris and D2Rhal, the structural information of D2Rspi should be of value for designing novel antipsychotics with improved safety and efficacy