Physiological Responses of Wheat Associate with Heat Tolerance

This study was performed to explore heat stress tolerance indices to judge terminal heat tolerance genotypes from nine wheat genotypes viz: AKAW 5023, AKAW 4927, PBN 4905, PBN 4751-02, NIAW 3523, NIAW 2891, AKAW 4210-6 (C), NIAW 34 (C), NIAW 1994 (C) at Wheat Research Unit, Dr. Panjabrao Deshmukh Krishi Vidyapeeth, Akola (MH) during Rabi 2016-17 and 2017-2018. The trial was setup in RBD design with three replications. Yield and Physiological traits were recorded and correlated with yield. Genotype NIAW 2891 noted significantly high germination %,CTD (4.30oC), minimum membrane thermo-stability index (48.86%) at 75 DAS (grain filling stage), exhibited more RGR (0.0074 g g-1 day-1), NAR (0.0500 g dm2 day-1), early 50% flowering (58.16 days), days to maturity (91.83 days) and more grain yield ha-1 (35.65 q/ha) followed by genotype NIAW 3523 (33.83 q/ha) during both the year and noted as heat tolerance genotypes against the best check AKAW 4210-6. Correlation analysis showed that yield under stress environment had positive significant correlate with days to 50 % flowering and physiological maturity however, canopy temperature and membrane thermo-stability index had negative significant correlation with yield. Hence, due emphasis should be given to these attributes for genetic improvement in wheat under heat stress condition.

Treatment of Connective Tissue Diseases-associated Interstitial Lung Disease by the Origin-restoring and Bi （痹）-alleviating Method / 中医杂志

It is believed that the fundamental pathogenesis of the connective tissue diseases-associated interstitial lung disease （CTD-ILD） is kidney essence deficiency， with lung collateral obstruction throughout the disease， and environmental toxin pathogen is the important causative factors for the development of CTD-ILD. This article proposed to restore origin and alleviate bi （痹） for CTD-ILD， for which restoring origin means tonifying the lungs， spleen and kidneys to bank up the roots and consolidate the original qi， with modified Erxian Decoction （二仙汤） plus Liu Junzi Decoction （六君子汤）； alleviating bi means expelling wind and dredging collaterals， and eliminating the mass to restore the smoothness of the lung collaterals， with paired medicines of Chuanshanlong （Dioscorea nipponica）-Dilong （Kalanchoe pinnata）， Vinegar-processed Sanleng （Sparganium stoloniferum）-Vinegar-processed Ezhu （Curcuma zedoaria）， and stem-type medicines， and emphasized on removing the environmental toxin pathogens to facilitate the recovery of healthy qi.

CircRNA-SCAF8 promotes vascular endothelial cell pyroptosis by regulating the miR-93-5p/TXNIP axis / 浙江大学学报·医学版

OBJECTIVES@#To investigate the role and mechanism of circRNA-SR-related CTD associated factor 8 (SCAF8) in regulating endothelial cell pyroptosis in high glucose environment.@*METHODS@#Human umbilical vein endothelial cells (HUVECs) were cultured and divided into six groups. The normal control group and high glucose control group were cultured in cell culture medium with 5 and 33 mmol/L glucose, respectively. The RNA control group, circRNA-SCAF8 inhibition group, miR-93-5p overexpression group and miR-93-5p inhibition group were added with non-functional siRNA, circRNA-SCAF8 inhibitor, miR-93-5p overexpression molecule and miR-93-5p inhibitor in high glucose environment, respectively. Cell viability and pyroptosis were detected by cell counting kit-8 (CCK-8) assay, flow cytometry and Hoechst 33342/propidium iodide fluorescence double staining. Western blotting and enzyme-linked immunosorbent assay were used to detect the expression of pyroptosis-related factors including apoptosis-associated speck-like protein containing a CARD (ASC), cysteine aspartic acid specific protease-1 (caspase-1) and Gasdermin D (GSDMD), NOD like receptor protein 3 (NLRP-3), thioredoxin interacting proteins (TXNIP), IL-18 and IL-1β. The expression of circRNA-SCAF8, miR-93-5p and TXNIP was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Fluorescence in situ hybridization (FISH) was used to locate circRNA-SCAF8 and miR-93-5p. Dual luciferase assay was used to verify the targeted regulatory relationship between miR-93-5p and upstream and downstream molecules.@*RESULTS@#Compared with the RNA control group, the cell survival rate of circRNA-SCAF8 inhibition group and miR-93-5p overexpression group increased (both P<0.01), the pyroptosis decreased (both P<0.01), and the expressions of pyroptosis-related factors such as TXNIP, NLRP-3, caspase-1, GSDMD, ASC, IL-18 and IL-1β were significantly decreased (all P<0.05). The expression of miR-93-5p was significantly increased after inhibition of circRNA-SCAF8 (P<0.01), and the expression of circRNA-SCAF8 tended to decrease after overexpression of miR-93-5p, but with no statistical significance (P>0.05). Dual luciferase assay showed that miR-93-5p downre-gulated circRNA-SCAF8 expression by binding to the 3 ´ UTR region of circRNA-SCAF8, and miR-93-5p downregulated TXNIP expression by binding to the 3 ´ UTR region of TXNIP. FISH showed that circRNA-SCAF8 and miR-93-5p were both located in the cytoplasm and were highly associated in the cells. qRT-PCR showed that the relative expression of TXNIP increased or decreased after overexpression or inhibition of miR-93-5p compared with the RNA control group, respectively (both P<0.05), suggesting that miR-93-5p could regulate TXNIP gene expression.@*CONCLUSIONS@#CircRNA-SCAF8/miR-93-5p/TXNIP axis is involved in the regulation of pyroptosis in HUVECs under high glucose.

Clinical Trial of Buyang Huanwutang in Treatment of Connective Tissue Disease-associated Pulmonary Fibrosis with Syndrome of Qi Deficiency and Blood Stasis / 中国实验方剂学杂志

ObjectiveTo evaluate the effect and safety of Buyang Huanwutang in treatment of connective tissue disease-associated pulmonary fibrosis in the patients with syndrome of Qi deficiency and blood stasis and explore the possible anti-fibrosis mechanism of Buyang Huanwutang. MethodSixty-six patients with connective tissue disease-associated pulmonary fibrosis with syndrome of Qi deficiency and blood stasis were randomized to receive either Buyang Huanwutang combined with routine therapy or routine therapy for 4 weeks. The primary outcome indicator was change in forced vital capacity （FVC） from the baseline， and the secondary outcome indicators included the changes in percentage of predicted forced vital capacity （FVC%pred）， percentage of forced expiratory volume in first second to predicted value （FEV1%pred）， King's Brief Interstitial Lung Disease （K-BILD） total score， 6 minute walking distance （6MWD）， hydroxyproline （HYP）， matrix metalloproteinase （MMP）， tissue inhibitor of metalloproteinase-1 （TIMP-1）， and transforming growth factor-β （TGF-β） from baseline. Patients in line with the inclusion criteria were included in the primary analysis， and sensitivity analysis was performed after multiple imputation of missing data. Safety set was adopted for safety analysis. ResultThe 66 patients （included in the sensitivity analysis） meeting the inclusion criteria included 34 in the observation group and 32 in the control group， and 60 patients finally received the whole trial intervention （included for primary analysis）. Compared with the baseline， the FVC increased in the observation group and decreased in the control group after intervention （P<0.01）， which was consistent between the sensitivity analysis and the primary analysis. The changes in FVC%pred， FEV1%pred， 6MWD， and K-BILD total score from baseline in the observation group were superior to those in the control group （P<0.01）， with consistent results between the sensitivity analysis and the primary analysis. TIMP-1 in the observation group decreased compared with baseline （P<0.05）， while TIMP-1 in the two groups showed no significant changes from the baseline The observation group outperformed the control group in the changes in HYP， MMP-9， and TGF-β from baseline （P<0.05）. The common adverse events were cough， diarrhea， nausea， rash， and upper gastrointestinal tract infection， the incidence of which showed no statistical difference between the two groups. ConclusionBuyang Huanwutang can improve lung function， motor function， and quality of life in patients with connective tissue disease-associated pulmonary fibrosis and has good safety. The mechanism may be related to the reduction of TGF-β， MMP-9， and TIMP-1 levels and maintaining of MMP-9/TIMP-1 balance.

Spatial and temporal dynamics of the hydrology at Salinas Bay, Costa Rica, Eastern Tropical Pacific / Dinámica espacial y temporal de la hidrología en Bahía Salinas, Costa Rica, Pacífico Tropical Oriental

Introduction: Salinas Bay is located in the warm pool of the Eastern Tropical Pacific (ETP), characterized by warm, shallow surface waters, a strong and shallow thermocline, and an important biological diversity. The primary productivity of the region is influenced by the coastal upwelling, which occurs during the boreal winter as a result of the strengthening of trade winds. Objective: To study the spatial and temporal dynamics of physical and chemical parameters at seven hydrographic stations in Salinas Bay, Costa Rica, through the analysis of CTD data, and relate the warm and cold events to the regional atmospheric conditions present when measuring the data. Methods: Seven hydrographic stations, sampled at Salinas Bay between August 2008 and December 2014, were selected. The variables processed for analysis are temperature, density, salinity, oxygen, chl-a and turbidity. Once the data was processed, 42 Hovmöller kind diagrams were plotted. Results: All variables, except turbidity, presented a seasonal periodicity associated with the upwelling. In general, colder and denser waters, higher salinity and chl-a concentrations and lower dissolved oxygen values were observed during the dry season, when the upwelling was active. Whereas, during the rainy season water masses were warmer and less dense, salinity and chl-a concentrations decreased and dissolved oxygen values tended to increase. Conclusions: The spatial and temporal dynamics of the hydrology in Salinas Bay was influenced by the coastal upwelling events. The region also presented an interannual variability associated with ENSO. Seasonal and interannual variability can counteract their effects on the oceanographic parameters when they coincide temporally.

Introducción: Bahía Salinas se encuentra embebida en la piscina de agua cálida del Pacífico Tropical Oriental (PTO) o del Este (PTE), caracterizada por aguas superficiales cálidas, poco salinas, una termoclina fuerte y poco profunda y una importante diversidad biológica. La productividad primaria de la región está influenciada por el afloramiento oceánico, el cual se presenta durante el invierno boreal como resultado del fortalecimiento de los vientos alisios. Objetivo: Estudiar la dinámica espacial y temporal de parámetros físico-químicos en siete estaciones hidrográficas en Bahía Salinas, Costa Rica, a través del análisis de datos de CTD; y relacionar los eventos cálidos y fríos con las condiciones atmosféricas presentes al medir los datos. Métodos: Se muestrearon y seleccionaron siete estaciones hidrográficas en Bahía Salinas entre agosto de 2008 y diciembre de 2014. Las variables procesadas para su análisis son temperatura, densidad, salinidad, oxígeno, clorofila-a y turbidez. Una vez procesados los datos se graficaron 42 diagramas tipo Hovmöller. Resultados: Todas las variables, excepto la turbidez, presentaron una periodicidad estacional asociada al afloramiento. En general, se observaron aguas más frías y densas, mayores concentraciones de salinidad y clorofila-a y valores menores de oxígeno disuelto durante la estación seca, cuando el afloramiento estaba activo. Por el contrario, durante la estación lluviosa las masas de agua eran más cálidas y menos densas, las concentraciones de salinidad y clorofila-a disminuyeron y los valores de oxígeno disuelto tendieron a aumentar. Conclusiones: La dinámica espacial y temporal de la hidrología en Bahía Salinas fue influenciada por los eventos de afloramiento costero. La región también presentó una variabilidad interanual, como la asociada con el ENOS. La variabilidad estacional y la interanual pueden contrarrestar sus efectos sobre los parámetros oceanográficos cuando coinciden temporalmente.

The disruption of protein-protein interactions with co-chaperones and client substrates as a strategy towards Hsp90 inhibition

The 90-kiloDalton (kD) heat shock protein (Hsp90) is a ubiquitous, ATP-dependent molecular chaperone whose primary function is to ensure the proper folding of several hundred client protein substrates. Because many of these clients are overexpressed or become mutated during cancer progression, Hsp90 inhibition has been pursued as a potential strategy for cancer as one can target multiple oncoproteins and signaling pathways simultaneously. The first discovered Hsp90 inhibitors, geldanamycin and radicicol, function by competitively binding to Hsp90's N-terminal binding site and inhibiting its ATPase activity. However, most of these N-terminal inhibitors exhibited detrimental activities during clinical evaluation due to induction of the pro-survival heat shock response as well as poor selectivity amongst the four isoforms. Consequently, alternative approaches to Hsp90 inhibition have been pursued and include C-terminal inhibition, isoform-selective inhibition, and the disruption of Hsp90 protein-protein interactions. Since the Hsp90 protein folding cycle requires the assembly of Hsp90 into a large heteroprotein complex, along with various co-chaperones and immunophilins, the development of small molecules that prevent assembly of the complex offers an alternative method of Hsp90 inhibition.

Distribución de temperatura y salinidad en campañas oceanográficas recientes en el Pacífico Tropical Oriental de Costa Rica / Distribution of temperature and salinity during recent oceanographic campaigns in the Eastern Tropical Pacific of Costa Rica

Introducción: Para Costa Rica, los estudios realizados en el Pacífico Tropical Este o PTE son importantes ya que se relacionan con el Corredor Marino del Pacífico Este Tropical, el cual es un esfuerzo de conservación multinacional. El presente estudio describe los parámetros físicos de temperatura del mar y salinidad del océano de las masas de agua que rodean a la Isla del Coco y su entorno, el PTE, a través del análisis de perfiles de CTD obtenidos durante campañas hidrográficas realizadas entre el año 2008 y el 2012; y comparar los resultados de los datos in-situ con los del reanálisis del modelo HYCOM-NCODA. Métodos: Se compilaron los resultados de 8 diferentes campañas científicas a la Isla del Coco de abril de 2008, marzo de 2009, abril de 2010, julio de 2011 y marzo de 2012. También se analizan las campañas de octubre de 2010 y marzo de 2011 en donde se realizó un transecto latitudinal y un transecto longitudinal en las aguas del Pacífico Tropical Este de Costa Rica. En julio de 2012 se realizaron 3 transectos latitudinales en las aguas en torno a la Isla del Coco. Las mediciones se hicieron por medio de un CTD, instrumento utilizado para determinar la conductividad, temperatura y presión de la columna de agua, entre otras variables. Resultados: Se observó la presencia de Agua Superficial Tropical en los primeros 50m de profundidad, con temperaturas superiores a 25°C y salinidades menores 33psu y Agua Sub-superficial Sub-tropical bajo los 60m con temperaturas menores a 25°C y salinidades alrededor de las 35ups. La zona de transición entre ellas se presentó entre los 50-60m. Los resultados de la temperatura del mar y la salinidad de los transectos analizados reflejan las condiciones climáticas y atmosféricas observadas, en donde se nota que las variaciones estacionales en el PTE están fuertemente influenciadas por la migración meridional de la Zona de Convergencia Inter-Tropical. Conclusiones: El estudio mostró que los datos del reanálisis del modelo de circulación general HYCOM-NCODA son comparables con los resultados de los perfiles del CTD en el PTE. La distribución de la temperatura de los muestreos tiende a ser similar a los datos del modelo oceánico y las principales diferencias se dan en la capa profunda para la salinidad, por lo que el modelo HYCOM es capaz de reproducir las características observadas en el PTE de temperatura y salinidad y puede ser usado para estudiar la dinámica tropical oceánica, en regiones más extensas y en otras épocas del año.

Introduction: In Costa Rica, studies done in the Eastern Tropical Pacific or ETP are important because of their interaction/relationship with the Eastern Tropical Pacific Seascape, a known multinational conservation initiative. The present study describes the physical parameters of sea temperature and salinity around Cocos Island and its environment, the ETP, using CTD profiles. Methods: Data were obtained in April 2008, March 2009, April 2010, July 2011 and March 2012 near this island. Latitudinal and longitudinal transects were also done during October 2010 and March 2011 in a broader Costa Rican ETP region. In July 2012, three latitudinal transects were done around Cocos Island. Records were obtained using a CTD, measuring conductivity, temperature and pressure, among other variables. Results: Tropical Surface Water was observed in the upper 50m, showing temperatures above 25°C and salinities below 33psu. Below the surface waters, Subsurface Subtropical Water was detected below a 60m depth, showing temperatures colder than 25°C and salinities around 35psu. The transition between these waters was around 50-60m in depth. Temperature and salinity results were related with the atmosphere conditions observed, in which ETP variability was strongly influenced by the Inter Tropical Convergence Zone migration. Conclusions: This study also showed that reanalysis data from the HYCOM-NCODA general circulation model are comparable and in a good agreement with the CTD profiles. Temperature and salinity HYCOM data also reproduced, in general terms, the main characteristics of CTD data, having some small differences in the deeper levels. This reanalysis data set could also be used to study the tropical ocean dynamics, in wider ETP regions and for different seasons.

Changes in Morpho-physiological and Yield Parameters of Rice (Oryza sativa L.) in Response to Ultraviolet-B (UV-B) Radiation

A rice variety Jyothi (PTB 39) is a red kernelled with bold grain, popular in the region of Kerala, India used in the study. Plants were grown in pots under three different conditions, natural solar UV-B conditions, UV-B excluded condition using UV-B filters and supplemental UV-B using UV-B lamps along with ambient solar radiation. During the study period, UV-B radiation was in the range of 1.30 to 3.58 Wm2 which affected the productivity of the crop under open solar condition. A decrease in morphological traits like plant height, number of tillers, flag leaf angle and increase in leaf thickness were observed. Physiological parameters, leaf gas exchange parameters and biochemical constituents such as chlorophyll content also recorded less value under high UV-B condition along with the high content of protective compounds such as flavonoid content, catalase and PAL activity. The phenophases of the crop were also delayed by 4-5 days under UV-B radiation exposed conditions. All these negative impacts of UV-B radiation on crop leads to restricted filling of grain, lesser harvest index and grain development leading to a decrease in yield and yield attributing characters.

Clinicoradiological Profile of Patients with Diffuse Parenchymal Lung Disease

The profile of diffuse parenchymal lung disease (DPLD) has mainly been reported from the developed countries; the prevalence and outcome of DPLD is not studied well across India. The aim of this study is to describe the clinical radiological spectrum of various DPLDs from a tertiary care centre of a developing country. Methods: An observational cross-sectional study was carried out in a single tertiary care center in northern India which included 50 consecutive subjects (age >12 years) who had diffuse parenchymal lung diseases. In this study, the clinical, radiological and histological data subjects was collected. Results: Out of the total 50 subjects, mean age was 49.04 years with females constituting 58% of the total. Most common symptoms were gradually progressing dyspnoea (100%) followed by dry cough (76%). The commonest finding on chest radiograph in our series was reticular pattern (78%).The commonest pattern on high-resolution computed tomography was traction bronchiectasis (56%), followed by honeycombing (50%), septal thickening (46%).The commonest cause of DPLD in study was Idiopathic Pulmonary Fibrosis (38) %, followed by connective tissue – interstitial lung disease (CTD-ILD)(26%) and NSIP(12%). Smoking was one of the major risk factor associated with IPF, and 52.6% of patients with IPF were smokers (P<0.001). Conclusion: IPF (38%) was the commonest DPLD seen followed by CTD- ILD and NSIP at a tertiary center in northern India similar to the spectrum reported from developed countries. More studies are required from developing countries to ascertain the spectrum of DPLDs in different geographic

A preliminary study on abnormal expression of long noncoding RNA CTD-2012K14.6 in placentas and its role in inducing macrosomia / 中华内分泌代谢杂志

Objective To explore the role of long noncoding RNA ( lncRNA) CTD-2012K14. 6 in the development of gestational diabetes mellitus (GDM) related macrosomia. Methods The quantitative real-time PCR ( qRT-PCR) was performed to measure the expression of CTD-2012K14.6 in placentas of women with or without GDM, and the quantity of CTD-2012K14. 6 expression and its association with fetal weights were analyzed; Bioinformatic analysis was performed to predict the downstream molecules. CTD-2012K14. 6 over-expressing lentiviral and siRNA was constructed in human trophoblastic cell line HTR-8/SVneo cells, qRT-PCR and Western blot (WB) were used to invest its effect in modulating the expression of downstream molecules. Results The expression of CTD-2012K14.6 in GDM placentas was significantly higher than that in normal controls (1.70 ± 0.63 vs 1.00 ± 0.56,t=3.68,P＜0.01), and positively correlated with fetal weight (r=0.8501, P＜0.01); on-line analysis showed that CTD-2012K14.6 was located at chr16:67,549,214-67,563,958, which was located in the intron of CCCTC-binding factor( CTCF); Up-regulating CTD-2012K14.6 could significantly reduce the expression of CTCF mRNA and protein, and increase the expression of insulin-like growth factor-Ⅱ( IGF-Ⅱ) mRNA and protein, while down-regulating CTD-2012K14.6 could significantly increase the expression of CTCF mRNA and protein, and reduce the expression of IGF-ⅡmRNA and protein. Conclusion The CTD-2012K14. 6 may play an important role in the pathogenesis of GDM related macrosomia by upregulating the expression of CTCF and IGF-Ⅱ.

Orthogonal assays for the identification of inhibitors of the single-stranded nucleic acid binding protein YB-1

We have previously shown that high expression of the nucleic acid binding factor YB-1 is strongly associated with poor prognosis in a variety of cancer types. The 3-dimensional protein structure of YB-1 has yet to be determined and its role in transcriptional regulation remains elusive. Drug targeting of transcription factors is often thought to be difficult and there are very few published high-throughput screening approaches. YB-1 predominantly binds to single-stranded nucleic acids, adding further difficulty to drug discovery. Therefore, we have developed two novel screening assays to detect compounds that interfere with the transcriptional activation properties of YB-1, both of which may be generalizable to screen for inhibitors of other nucleic acid binding molecules. The first approach is a cell-based luciferase reporter gene assay that measures the level of activation of a fragment of the promoter by YB-1. The second approach is a novel application of the AlphaScreen system, to detect interference of YB-1 interaction with a single-stranded DNA binding site. These complementary assays examine YB-1 binding to two discrete nucleic acid sequences using two different luminescent signal outputs and were employed sequentially to screen 7360 small molecule compounds leading to the identification of three putative YB-1 inhibitors.

A study on the safety and tolerability of mycophenolate mofetil in patients with connective tissue disease

Background: Connective tissue disorders (CTD) are mostly due to inflammatory and fibrotic tissue injury. Glucocorticoids and immunomodulators though useful but are toxic. Mycophenolate mofetil (MMF) is now being used successfully in many autoimmune diseases, but the safety of MMF in CTD patients is yet to be conclusively established.Methods: The study was a retrospective record based observational one in patients of CTD satisfying the predetermined inclusion criteria. Various safety parameters were noted down from the observed records and analysed accordingly.Results: The 120 case records of CTD patients were analysed for a specific set of safety parameters over the preceding one year. Diarrhoeal attacks were the most commonly encountered side effect (38.3%) of long term patients who were on mycophenolate therapy followed by infection.Conclusions: Mycophenolate was found to be generally well tolerated in CTD patients with few reports of adverse events, but larger clinical trials are needed to conclusively establish its safety.

Propuesta de requisitos armonizados para el registro sanitario de productos biológicos en la República Bolivariana de Venezuela / Proposal for harmonized requirements for the sanitary registration of biological products in the Bolivarian Republic of Venezuela

La Autoridad Nacional Reguladora en la República Bolivariana de Venezuela en el área de registro y control de medicamentos es el Instituto Nacional de Higiene "Rafael Rangel" (INHRR). Para el cumplimento de estas funciones cuenta con normativas y requisitos específicos para las vacunas, hemoderivados y afines, y productos biológicos terapéuticos. A nivel mundial existen organismos como la Conferencia Internacional de Armonización de Requisitos Técnicos para el Registro de Medicamentos de Uso Humano (ICH) y la Red Panamericana para la Armonización de la Reglamentación Farmacéutica (Red PARF) que se encargan de establecer recomendaciones para favorecer la armonización de la reglamentación farmacéutica. El objetivo del presente trabajo fue elaborar una propuesta de requisitos armonizados para el registro de productos biológicos, ajustada a los requisitos establecidos por el INHRR, la ICH y la Red PARF, considerando los aspectos específicos de cada tipo de producto, dada su naturaleza, materiales de partida, proceso de fabricación, métodos de ensayos necesarios para su control y los requisitos legales para solicitar el registro sanitario. Esta propuesta de armonización que considera los requisitos internacionales para registro de productos favorece la disponibilidad de los mismos a nivel nacional garantizando su calidad, seguridad y eficacia.

The National Authority for Regulatory Affairs in the Bolivarian Republic of Venezuela in the areas of registration and control of drugs is the National Hygiene Institute "Rafael Rangel" (INHRR for the spanish acronyms). For the completion of their functions, it has regulations and requirements for vaccines, blood products and related and biological therapeutics products. Worldwide, there are organizations like the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and the Pan American Network for Drug Regulatory Harmonization (PARF Network) that are responsible for setting recommendations for promoting the harmonization of drugs regulations. The Objective of this study was to develop a proposal for harmonize the requirements for the registration of biological products, conforming to the requirements of the INHRR, the ICH and PARF Network, considering the specifics of each type of product, according its nature, materials base, manufacturing processes, testing methods necessary to control and legal requirements to request his registration. This proposal considers harmonization with international requirements for product registration ensuring the availability of the products at national level in order to ensure the quality, safety and efficacy.

Experimental Study on Carpal Tunnel Syndrome as a Cumulative Trauma Disorder

OBJECTIVE: To study the reaction of tissues in the carpal tunnel after repeated flexion of wrist in order to verify the pathophysiology and pathomechanism of the carpal tunnel syndrome as a cumulative trauma disorder. METHOD: Six groups of adult rabbits (5 rabbits were allocated to each groups) were exposed to repeated contractions of the wrist flexors by the median nerve stimulation at the elbow level for different durations; 2 days, 1 week, 2 weeks, 3 weeks, 4 weeks, and 5 weeks. Histological evaluation, morphometric analysis, and electrophysiological studies were carried out after the stimulation. RESULTS: There were no typical nor consistent findings in the tissues in the carpal tunnel except the median nerve. Inflammatory cell infiltration and edematous changes were noted in the epineurial tissue of median nerve. Decrease of large myelinated fibers and changes of fiber shape were observed in the median nerve. On the morphometric analysis, fiber diameter was smaller in groups of longer exposure duration. Changes were most prominent in 5 weeks group and in the periphery of the nerve fascicle in all the groups. Significant reduction of amplitude and increase of duration of compound muscle action potential were noted on electrophysiological study of the median nerve. CONCLUSION: The authors concluded that repeated experimental wrist flexion could give rise to an injury of the median nerve in the carpal tunnel. Accumulation of microtrauma of median nerve by epineurial edema and direct mechanical compression seems to be the pathomechanism of the carpal tunnel syndrome as a cumulative trauma disorder.

The Prevalence and Ergonomic Analysis of Cumulative Trauma Disorders in the Bank Worker and Post Officer

OBJECTIVE: To survey the prevalence of Cumulative trauma disorders (CTDs) and to analyze the ergonomic factors among the bank workers and post officers. METHOD: Seventy seven subjects were collected from bank workers (50) and post officers (27) from the multiple areas of country who had been exposed to risky working environment regarding CTDs. The subjects were first screened by occupational medicine specialists and confirmed by rehabilitation medicine specialist. The serologic test, radiologic imaging, electrodiagnostic study were performed in all the subjects. Ergonomists analyzed the job element to identify the risk factors by baseline checklist of CTDs. RESULTS: Among bank workers, 30 (60%) of 50 were confirmed as having CTDs. MPS was present in 30 patients (60%), latenl epicondylitis in 5 (10%), medial epicondylitis in 3 (6.0%), tendinitis 3 (6.0%), and other disease in 3 (6.0%). Among post officers, 14 (51.9%) of 27 were confirmed as having CTDs. MPS present in 10 (37.0%), cervical disc disease in 4 (14.8%), others in 4 (14.8%). The ergonomic risk score was highest 1.87 in the 'package deviding' job, and 1.82 in 'bagging to cart', 1.62 in 'initial devision'. CONCLUSION: The result would be helpful for the prevention and management of CTDs in the bank workers and post officers.

The effectiveness of the intervention in the workplace on patients suffering from Cervicobrachial disorder / 대한산업의학회지

OBJECTIVES: In order to reveal the effectiveness of the intervention in the workplace on patients suffering from cervicobrachial disorder (CBD), we reexamined 96 workers out of 137 workers suffering from CBD on the assembly lines of an electric manufacturing factory by using questionnaires, physical exams and neurological exams. METHODS: Analyses were made of the characteristics of the 96 workers of this company suffering from 1994 to 1996 with special concern for differences before and after the improvement of the working environment. After reexamination of the 96 patients the following results were obtained. RESULTS: We observed an improvement in the 10 most common subjective symptoms of CBD. These symptoms included general fatigue, pain on neck and shoulders, dullness of the upper extremities, back pain and discomfort and a tingling sensation in the hands and wrists (p < 0. 05). The percentage of workers who complained muscle tenderness of neck and shoulder were reduced (p < 0.05). the percentage of workers with abnormal Morley examination was reduced from 28. 5% to 2. 100 (p < 0.01), and of workers with abnormal EMG finding went from 12. 4% to 2. lao (p < 0. 01) and of grade 3 and grade 4 CBD was reduced from 42. 3% and 18. 3% respectively to 33. 3% and 2. ba (p < 0. 01). Grade 3 and over laborers of CBD had higher scores in somatization, anxiety, depression, hostility, interpersonal sensitivity, phobic anxiety, obsessive-compulsive, neurasthenic, hypochondriacal than other sufferers in the SCL-90-R exam (p < 0. 01). CONCLUSIONS: in conclusion intervention had effectiveness on subjective symptoms of neck and shoulder and decreasing abnormal finding of muscle tenderness, neurological examination and EMG.

The Relation Between Work-Related Musculoskeletal Symptoms and Rapid Upper Limb Assessment(RULA) among Vehicle Assembly Workers / 예방의학회지

OBJECTIVES: This study was conducted to evaluate the association between upper extremity musculoskeletal symptoms and Rapid Upper Limb Assessment(RULA) in vehicle assembly line workers. The goal of this study is to show the feasibility of RULA as a checklist for work related musculoskeletal symptoms (WMSDs) in Korean workers. METHODS: The total number of 199 people from the department of assembly and 115 people from the department of Quality Control(QC) in automotive plant were subjects for this cross sectional study. A standard symptom questionnaire survey has been used for the individual characteristics, work history, musculosketal symptoms and non-occupational covariates. The data were obtained by applying one-on-one interview for the all subjects. RULA has been applied for ergonomic work posture analysis and the primary ergonomic risk score was computed by RULA method. Association between upper extremity musculoskeletal symptoms and RULA were assessed by multiple logistic regression analysis. RESULTS: A total of 314 workers was examined. The prevalence of musculoskeletal symptoms by NIOSH case definition was 62.4%. The distribution of musculoskeletal symptoms by the part of the body turned out to be following; back:41.4%, neck: 32.8%, shoulder: 26.4%, arm: 10.5% and hand:29.3%. The relationship of the individual RULA scores were statistically significant for the prevalence of musculoskeletal symptoms. As the result of the multiple logistic regressioin analysis, grand final score (OR=2.250 95% CI: 1.402-3.612) was associated with musculoskeletal symptoms in any part of the body.; upper arm score(OR=1.786 95% CI: 1.036-3.079) and posture score A(OR=1.634 95% CI: 1.016-2.626) in neck; muscel use score(OR=3.076 95% CI:1.782-5.310) and posture score A(OR=1.798 95% CI: 1.072-3.017) in shoulder; upper arm score(OR=1.715 95% CI: 1.083-2.715) and muscel use score(OR=2.057 95% CI:1.303-3.248) in neck & shoulder; muscle use score(OR=10.662 95% CI: 3.180-35.742) in arm; writst/twist score(OR=2.068 95% CI: 1.130-3.786) and muscle use score(OR=2.215 95% CI: 1.284-3.819) in hand & wrist.; muscle use score of trunk (OR=2.601 95% CI: 1.147-5.901) in back. CONCLUSIONS: Musculoskeletal symptoms of the upper extremities were strongly associated with individual RULA body score. These results show that RULA can be used as a useful assessment tool for the evaluation of musculoskeletal loading which is known to contribute to work-related musculoskeletal disorders. RULA also can be used as a screening tool or incorporated into a wider ergonomic assessment of epidemiological, physical, mental, environmental and organizational factors. As shown in this study, complement of the analysis system for the other risk factors and characterizing between the upper limb and back part will be needed for future work.