A First-in-human, Double-blind, Placebo-controlled, Phase 1 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Intravenous Doses of HM201 (Pegylated Human Adrenomedullin) in Healthy Subjects (Adults)

This will be a single centre, Phase 1, Placebo-controlled, Randomized, Doubleblind, SAD & MAD Study to Assess the Safety, Tolerability and PK of HM201 in Healthy Subjects.

开始日期2021-11-11

申办/合作机构

Syneos Health, Inc.

[+1]

NCT02216279 / Completed临床2期IIT

Phase-II Study of the Use of PulmoBind for Molecular Imaging of Pulmonary Hypertension

Pulmonary hypertension or elevation of the pressure in the pulmonary vessels, results from various clinical conditions. It may be idiopathic (of unknown cause) or associated with numerous diseases including cardiovascular and lung disorders. Affected individuals suffer from progressive shortness of breath and, in its most sever forms; pulmonary hypertension carries a worse prognosis than many types of cancer. There is no test currently that can easily and non-invasively detect abnormalities of the pulmonary circulation. Presently there is no cure for pulmonary hypertension and substantial research efforts are dedicated to the development of new drugs that will stop progression or better yet, reverse the disease process. The investigators do not know if any of the drugs currently commercialized for pulmonary hypertension directly improve the status of the pulmonary vessels since no test currently provides this information. Direct earlier detection of lung vessel abnormalities associated with pulmonary hypertension using a sensitive and non-invasive test would allow not only earlier testing of these and of new drugs, but would provide a much better surrogate of disease severity allowing more efficient pre-clinical drug testing. The aim of this phase II study is to evaluate the safety of PulmoBind in participants with pulmonary hypertension and its potential to detect abnormal pulmonary circulation associated within pulmonary hypertension.

开始日期2014-09-01

申办/合作机构

Montréal Heart Institute

NCT01539889 / Completed临床1期IIT

Phase-I Study of Radiolabeled DFH-12 (PulmoBind) for Molecular Imaging of the Pulmonary Circulation

Pulmonary hypertension (PH) can be the result of various clinical conditions. It may be idiopathic or associated with various cardiovascular and lung disorders. Currently there is no test that can non-invasively detect abnormalities of the pulmonary circulation. There is a growing need for a non-invasive method to detect PH. There currently exists only ne agent approved in Canada for clinical imaging of the pulmonary circulation, 99mTc-labeled macroaggregates. This agent is exclusively used for the diagnosis of physical defects of the circulation due to pulmonary embolus. This agent is larger than small pulmonary vessels, limiting its sensitivity to detect small vascular defects, as well as potential infectious risks since albumin macroaggregates are derived from human albumin. There is need then for new lung tracers that could provide a greater safety profile while enabling functional as well as anatomical imaging of the pulmonary circulation. DFH-12 (PulmoBind) is a peptide derived from human adrenomedullin (hAMI-52). Hence the development of this novel AM derivative, PulmoBind, for molecular imaging of the pulmonary circulation. PulmoBind is labeled with 99mTc, the most commonly used imaging isotope in nuclear medicine.

开始日期2011-12-01

申办/合作机构

Montréal Heart Institute

100 项与 ADMR 相关的临床结果

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100 项与 ADMR 相关的转化医学

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0 项与 ADMR 相关的专利（医药）

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244

项与 ADMR 相关的文献（医药）

2024-09-01·Plant Disease

Colletotrichum aeschynomenes Causing Anthracnose in Combretum indicum in Guangxi, China

Article

作者: Guo, Tangxun ; Li, Qili ; Huang, Suiping ; Tang, Lihua ; Wang, Rui ; Chen, Xiaolin ; Sun, Wenxiu ; Ouyang, Dan

Combretum indicum（L.）Jongkind, distributed in Southeast Asia, is widely planted in southern China for its ornamental and medicinal value. In February 2023, anthracnose symptoms were observed on C. indicum leaves in Nanning Garden Expo (N22°43′, E108°28′), Guangxi, China, causing severe defoliation of infected plants with a foliar disease incidence ranging from 40 to 60% (n = 100) in a 2 ha field. Disease symptoms began with small red spots (2 to 3 mm by 2 to 3 mm) on the leaves and gradually enlarged to larger irregular light grey lesions with yellowish halos (3 to 5 mm by 2 to 8 mm). In the late stage, spots merged into larger irregular lesions (5 to 15 mm by 6 to 13 mm) and the necrotic lesions abscised. Three diseased samples in total were collected from plants in three different locations. Symptomatic leaves were cut into small pieces (3×3 mm), disinfected with 75% ethanol solution for 10 s, 2% NaClO for 1 min followed by three washes in sterile distilled water. Tissue pieces were separately plated on potato dextrose agar (PDA) and incubated at 25°C for five days. One representative isolate from each sample (SJ-1, SJ2-1 and SJ3-1) were chosen for further analysis. Colonies were villiform, initially white, later turning gray in 7 days on PDA at 25℃. The average diameter for colonies were 8.1 cm, 8.0 cm and 8.1 cm for SJ1-1, SJ2-1 and SJ3-1, respectively. Conidia were aseptate, hyaline, cylindroid, and averaged 11.94 μm × 5.04 μm, 11.78 μm × 5.14 μm and 11.74 μm × 4.59 μm (n=90) for SJ1-1, SJ2-1 and SJ3-1, respectively. The characteristics were close to the descriptions of Colletotrichum spp. (Weir et al. 2012). Genomic DNA was extracted from 7-day-old aerial mycelia of these isolates. The internal transcribed spacer (ITS), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), actin (ACT), β-tubulin (TUB2), chitin synthase (CHS-1), calmodulin (CAL) and the intergenic region between apn2 and MAT1-2-1 (ApMat) were amplified using primers ITS1/ITS4 (White et al. 1990), GDF/GDR, ACT-512F/ACT-783R, T1/Bt2b, CHS-79F/CHS-354R, CL1C/CL2C (Weir et al. 2012) and AM-F/AM-R (Silva et al. 2012), respectively. Sequences were deposited in GenBank (ITS: OR540240-OR540242; GAPDH: PP328968-PP328970; ACT: PP328959-PP328961; TUB2: PP328971-PP328973; CHS-1: PP328965-PP328967; CAL: PP328962-PP328964 and ApMat: OR548253-OR548255). A phylogenetic analysis was made via Bayesian inference based on the concatenated sequences (ITS, GAPDH, ACT, TUB2, CHS-1, CAL and ApMat). According to morphology and phylogenetic analysis, SJ1-1, SJ2-1 and SJ3-1 were identified as C. aeschynomenes. Pathogenicity was confirmed on leaves with and without wounds of 24 one-year-old C. indicum plants in a greenhouse in Nanning, Guangxi Province. The wound was made with a sterilized needle. Wounded and unwounded leaves were inoculated with 20 μl of conidial suspension (106 spores/ml in 0.1% sterile Tween 20) of the three isolates and control plants were inoculated with water containing 0.1% sterile Tween 20 (6 leaves/plant, 3 plants/treatment). All plants were covered with plastic bags to maintain a high humidity environment and placed in a 28°C growth chamber with constant light. After 7 days of incubation, necrotic lesions were observed on inoculated wounded leaves, whereas unwounded leaves and control plants showed no symptoms. The fungi were re-isolated from symptomatic leaves, completing Koch’s postulates. These species can cause severe diseases in a variety of plants worldwide, such as Manihot esculenta, Theobroma cacao and Myrciaria dubia (Sangpueak et al. 2018; Nascimento et al. 2019; Matos et al. 2020). To our knowledge, this is the first report of C. aeschynomenes causing C. indicum leaf anthracnose in China. The results will provide valuable information for management of anthracnose in C. indicum.

2023-12-01·Journal of Peptide Science

Rational design of highly stabilized and selective adrenomedullin analogs

Article

作者: Bierer, Donald ; Riedl, Bernd ; Flamme, Ingo ; Jülke, Eva-Maria ; Fischer, Jan-Patrick ; Köbberling, Johannes ; Els-Heindl, Sylvia ; Beck-Sickinger, Annette G

The peptide hormone adrenomedullin (ADM) consists of 52 amino acids with a disulfide bond and an amidated C‐terminus. Due to the vasodilatory and cardioprotective effects, the agonistic activity of the peptide on the adrenomedullin 1 receptor (AM1R) is of high pharmacological interest. However, the wild‐type peptide shows low metabolic stability leading to rapid degradation in the cardiovascular system. Previous work by our group has identified proteolytic cleavage sites and demonstrated stabilization of ADM by lipidation, cyclization, and N‐methylation. Nevertheless, these ADM analogs showed reduced activity and subtype selectivity toward the closely related calcitonin gene‐related peptide receptor (CGRPR). Here, we report on the rational development of ADM derivatives with increased proteolytic stability and high receptor selectivity. Stabilizing motifs, including lactamization and lipidation, were evaluated regarding AM1R and CGRPR activation. Furthermore, the central DKDK motif of the peptide was replaced by oligoethylene glycol linkers. The modified peptides were synthesized by Fmoc/t‐Bu solid‐phase peptide synthesis and receptor activation of AM1R and CGRPR was measured by cAMP reporter gene assay. Peptide stability was tested in human blood plasma and porcine liver homogenate and analyzed by RP‐HPLC and MALDI‐ToF mass spectrometry. Combination of the favorable lactam, lipidation, ethylene glycol linker, and previously described disulfide mimetic resulted in highly stabilized analogs with a plasma half‐life of more than 144 h. The compounds display excellent AM1R activity and wild‐type‐like selectivity toward CGRPR. Additionally, dose‐dependent vasodilatory effects of the ADM derivatives lasted for several hours in rodents. Thus, we successfully developed an ADM analog with long‐term in vivo activity.

2023-10-01·Plant Disease

First Report of Anthracnose on Dioscorea opposita Caused by Colletotrichum siamense in Guangdong Province in China

Article

作者: Ren, Lei ; Hu, Han ; Zhang, Le ; Wang, Yan ; Luo, Tu ; Weng, Li

Yam is the world's fourth most important tuber crop, after cassava, potato, and sweet potato in the world, the cultivation area of yam from the Food and Agriculture Organization of the United Nations Statistics Division database (FAOSTAT) is about 8,831,037 ha in 2020. Chinese yam (Dioscorea opposita Thunb.) is an economically important root crop throughout China due to its high economic and medicinal value. South China including Guangdong and Guangxi provinces is one of the important production districts of Chinese yam with economic value. A disease affecting the leaves was observed on yam leaves in August 2021 with an incidence of 20 to 90% in Guangdong and Guangxi provinces. Symptoms start as pinpoint lesions on yam leaves which enlarged to oval spots and large irregular spots. The spots were brown and surrounded by a chlorotic halo with sunken cavities, which are typical symptoms of anthracnose. To identify the causal agent, 9 symptomatic leaves from 3 different districts were collected in Guangdong and Guangxi provinces. Leaf samples were disinfested with 1% NaOCl for 3 min, and cultured on potato dextrose agar (PDA) at 28 °C for 3 days week. 9 single-spore isolates were recovered from each PDA medium. Colonies on PDA were grayish white with bright orange conidial spore masses. Fungal mycelia were hyaline, septate, and branched. Conidia were born on a long conidiogenous cell, straight, hyaline and cylindrical with rounded ends, 5.3 to 6.8×15.2 to 21.3μm (n = 50). Appressoria were dark, smooth-walled, oval in shape. The isolates were morphologically identified as Colletotrichum sp. (Weir et al. 2012). 3 strains were used for the pathogenicity test, 5 plants at creeping stage were inoculated with each isolate separately and 3-5 leaves of each plant were inoculated. Fresh wounds were made with a sterile needle on the healthy surface of yam leaves and each leaf was covered with a piece of cotton drenched with conidial suspension (106 conidia/mL) from each isolate. Control seedlings were inoculated identically except sterile water was used. Inoculated plants were placed in a moisturizing light incubator at 25℃ and 80% humidity under a 12-h light/dark cycle for 7 days and examined daily to monitor disease symptom development. Small round brown spots were observed at the inoculation sites 3 days after the inoculation and eventually became large brown lesions. No symptoms wre observed in the water-inoculated plants. A Colletotrichum sp. strain based on morphology was reisolated from inoculated leaves, fulfilling Koch's postulates. For molecular identification, the direct colony PCR method (Lu et al. 2012) was used to amplify the internal transcribed spacer (ITS) region of ribosomal DNA, calmodulin (Cal), tubulin (Tub) and Apmat loci of three isolates using primer pairs of ITS4/ITS5, CL1C/CL2C, T1/T2 and AM-F/AM-R (Sharma et al. 2015). A phylogenetic tree derived from a maximum likelihood analysis of a concatenated alignment of ITS, Cal, Tub and ApMAT sequences was created. The accession numbers of the three isolates YamZJCS, YamSXCS and YamYLCS used in this study were OP128056-OP128058 for ITS, OP128059-OP128061 for ApMAT，OP128062-OP128064 for Cal and OP128065-OP128067 for Tub. The sequences of the 3 isolates were aligned with related species of Colletotrichum (Sharma et al. 2015). Analyses based on concatenated data sets of 4 genes showed that the sequences had high levels of identity to that of the C. siamense strains. According to both morphological and sequence analyses, the pathogen was identified as C. siamense. There were reports of anthracnose on yam caused by Colletotrichum sp. in Guangxi (Zhu et al. 2007), Hainan (Lin et al. 2018) and Jiangsu (Han et al. 2020) provinces in China. To our knowledge, this is the first report of anthracnose on D. opposita caused by C. siamense in Guangdong province in China.