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公开(公告)号：US07045124B1
公开(公告)日：2006-05-16
申请号：US09480260
申请日：2000-01-11
IPC分类号： A01N63/00
CPC分类号： A61M1/3681 , A61M1/32 , A61M1/3683 , A61M1/3687 , A61M1/369 , A61M2202/0216 , A61M2205/053 , A61N2005/0661
摘要： Apoptosis and/or necrosis related disorders in the mammalian body, namely radiation exposure disorders, chemical exposure and ingestion disorders, neurological disorders and physical trauma disorders, are treated, and their onset is counteracted by preconditioning, by extracting from the mammalian body an aliquot of blood, subjecting the extracted aliquot, ex vivo, to an oxidative stressor such as exposure to ozone gas, a temperature stressor, i.e. temperatures above or below body temperatures, and ultraviolet light, and re-injecting the treated blood aliquot into the mammalian body. The treatment ha the effect of decreasing apoptosis/necrosis in the body, and of pre-conditioning the body better to withstand subsequently encountered apoptosis-inducing events.
摘要翻译： 治疗哺乳动物体内的细胞凋亡和/或坏死相关疾病，即放射线暴露障碍，化学暴露和摄取障碍，神经系统疾病和身体创伤障碍，并通过预处理抵消其发作，通过从哺乳动物体内提取等分试样 血液，将提取的等分试样离体处理到氧化应激源，例如暴露于臭氧气体，温度应激器，即高于或低于体温的温度和紫外线，并将经处理的血液等分试样重新注射到哺乳动物体内。 这种治疗方法是减少身体凋亡/坏死的作用，并且更好地预处理身体，以抵御随后遇到的凋亡诱导事件。
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公开(公告)号：US5326551A
公开(公告)日：1994-07-05
申请号：US634220
申请日：1991-02-05
申请人： Pavel Hamet , Johanne Tremblay , Raymond Lamberet , Jean Leveille
发明人： Pavel Hamet , Johanne Tremblay , Raymond Lamberet , Jean Leveille
CPC分类号： A61K51/08 , A61K2123/00
摘要： Uptake, binding, and/or displacement of atrial natriuretic factor in a target organ of a mammal can be quantified by nuclear imaging. A diagnostically effective amount of a radio-labelled mammalian atrial natriuretic factor, active fragment or analog thereof is administered to a live mammal, and the live mammal or a portion thereof is subsequently imaged at one or more time intervals using a suitable radio-detecting device to quantify the uptake, binding and/or displacement of the radio-labelled atrial natriuretic factor, fragment or analog in one or more target organs.
摘要翻译： PCT No.PCT / CA90 / 00192 Sec。 371日期：1991年2月5日 102（e）日期1991年2月5日PCT Filed 1990年6月8日PCT公布。 第WO90 / 14845号公报 1990年12月13日。哺乳动物靶器官中心房钠尿因子的摄取，结合和/或置换可以通过核成像进行量化。 向活的哺乳动物施用诊断有效量的放射性标记的哺乳动物心房钠尿素因子，其活性片段或类似物，并且随后使用合适的放射线检测装置以一个或多个时间间隔对活的哺乳动物或其一部分进行成像 定量放射性标记的心房利钠因子，片段或类似物在一个或多个靶器官中的摄取，结合和/或置换。
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公开(公告)号：US20070238788A1
公开(公告)日：2007-10-11
申请号：US11643946
申请日：2006-12-22
申请人： Wendy Hauck , Pavel Hamet
发明人： Wendy Hauck , Pavel Hamet
IPC分类号： A61K31/185
CPC分类号： A61K31/10 , A61K31/185
摘要： Disclosed herein are methods, compounds and compositions for preventing or treating a renal disorder or chronic kidney diseases, including nephropathies such as diabetic nephropathy. The invention generally includes administering to a subject 1,3-propanedisulfonic acid or a pharmaceutically acceptable salt thereof, e.g., 1,3-propanedisulfonic acid sodium salt. The invention also relates to methods, compounds and compositions for the prevention and/or treatment of for preventing or treating a renal disorder complication. The invention further relates to methods, compounds and compositions for the prevention and/or treatment of dyslipidemia, and more particularly for reducing levels of harmful serum lipid levels, especially cholesterol and triglycerides in diabetic patients.
摘要翻译： 本文公开了用于预防或治疗肾病或慢性肾脏疾病（包括肾病如糖尿病肾病）的方法，化合物和组合物。 本发明通常包括向受试者施用1,3-丙二磺酸或其药学上可接受的盐，例如1,3-丙二磺酸钠盐。 本发明还涉及用于预防和/或治疗预防或治疗肾病并发症的方法，化合物和组合物。 本发明还涉及用于预防和/或治疗血脂异常的方法，化合物和组合物，更具体地涉及降低糖尿病患者中有害血清脂质水平，特别是胆固醇和甘油三酯的水平。
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4.发明授权Uses of ouabain and ouabain-like molecules in apoptosis related pathologies 失效哇巴因和哇巴因分子在凋亡相关病理学中的应用公开(公告)号：US06699676B1
公开(公告)日：2004-03-02
申请号：US09586097
申请日：2000-06-02
申请人： Sergei N. Orlov , Pavel Hamet , Johanne Tremblay
发明人： Sergei N. Orlov , Pavel Hamet , Johanne Tremblay
IPC分类号： G01N33567
CPC分类号： A61K31/7048 , A61K31/704 , A61K31/7042
摘要： Longterm elevation of the intracellular Na+/K+ ratio inhibits macromolecule synthesis and proliferation in the majority of cell types studied so far, including vascular smooth muscle cells (VSMC). We report here that inhibition of the Na+,K+ pump in VSMC by ouabain or 1 hour preincubation in K+-depleted medium attenuated apoptosis triggered by serum withdrawal, staurosporine or okadaic acid. In the absence of ouabain, both DNA degradation and caspase-3 activation in VSMC undergoing apoptosis were insensitive to modification of the extracellular Na+/K+ ratio as well as to hyperosmotic cell shrinkage. In contrast, protection of VSMC from apoptosis by ouabain was abolished under equimolar substitution of Na+o with K+o, showing that the anti apoptotic action of Na+,K+ pump inhibition was caused by inversion of the intracellular Na+/K+ ratio. Unlike VSMC, the same level of increment of the [Na+]i/[K+]i ratio caused by 2 hours preincubation of Jurkat cells with ouabain did not affect chromatin cleavage and caspase-3 activity triggered by treatment with Fas ligand, staurosporine or hyperosmotic shrinkage. Thus, our results show for the first time that similarly to cell proliferation, maintenance of a physiologically low intracellular Na+/K+ ratio is required for progression of VSMC apoptosis.
摘要翻译： 细胞内Na + / K +比例的长期升高抑制了迄今为止研究的大多数细胞类型（包括血管平滑肌细胞（VSMC））的大分子合成和增殖。 我们在这里报告说，通过哇巴因在血管平滑肌细胞中抑制Na +，K +泵或在K +消耗性介质中1小时预孵育减少由血清戒断，星形孢菌素或冈田酸引起的细胞凋亡。 在没有哇巴因的情况下，经历凋亡的VSMC中的DNA降解和半胱天冬酶-3激活对细胞外Na + / K +比的改变以及高渗细胞收缩都不敏感。 相比之下，在K + O等摩尔Na +取代的情况下，哇巴因对VSMC的凋亡的保护被消除，表明Na +，K +泵抑制的抗凋亡作用是由反转引起的 的细胞内Na + / K +比。 与VSMC不同，Jurkat细胞与哇巴因预处理2小时引起的[Na +] i / [K +] i比例的增加水平不会影响染色质切割和由治疗引起的半胱天冬酶-3活性 Fas配体，星形孢菌素或高渗收缩。 因此，我们的研究结果首次表明，与细胞增殖类似，VSMC凋亡进展需要维持生理学上低的细胞内Na + / K +比。
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公开(公告)号：US20080200414A1
公开(公告)日：2008-08-21
申请号：US11938894
申请日：2007-11-13
摘要： Novel nucleic acids and corresponding encoded proteins are described. Also described are corresponding recombinant vectors and host cells, as well as methods of producing the proteins. Also described are mimetics and antibodies to the proteins as well as compositions comprising the nucleic acid or proteins or a portion thereof. Methods and kits for the detection of a disease, disorder or abnormal physical state caused by abnormal modulation of calcium levels in a patient are also described. Methods for treating a patient having a disease, disorder or abnormal physical state caused by abnormal calcium levels are also described. Methods for assaying abnormal calcium levels are also described, as are methods for screening the efficacy of products for modulating abnormal calcium levels.
摘要翻译： 描述了新的核酸和相应的编码的蛋白质。 还描述了相应的重组载体和宿主细胞，以及产生蛋白质的方法。 还描述了模拟物和蛋白质的抗体以及包含核酸或蛋白质或其一部分的组合物。 还描述了用于检测由患者中钙水平的异常调节引起的疾病，病症或异常身体状态的方法和试剂盒。 还描述了治疗由异常钙水平引起的疾病，病症或异常身体状况的患者的方法。 还描述了测定异常钙水平的方法，以及用于筛选产物用于调节异常钙水平的功效的方法。
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公开(公告)号：US20060127383A1
公开(公告)日：2006-06-15
申请号：US11347059
申请日：2006-02-02
CPC分类号： A61M1/3681 , A61M1/32 , A61M1/3683 , A61M1/3687 , A61M1/369 , A61M2202/0216 , A61M2205/053 , A61N2005/0661
摘要： Apoptosis and/or necrosis related disorders in the mammalian body, namely radiation exposure disorders, chemical exposure and ingestion disorders, neurological disorders and physical trauma disorders, are treated, and their onset is counteracted by preconditioning, by extracting from the mammalian body an aliquot of blood, subjecting the extracted aliquot, ex vivo, to an oxidative stressor such as exposure to ozone gas, a temperature stressor, i.e. temperatures above or below body temperatures, and ultraviolet light, and re-injecting the treated blood aliquot into the mammalian body. The treatment ha the effect of decreasing apoptosis/necrosis in the body, and of pre-conditioning the body better to withstand subsequently encountered apoptosis-inducing events.
摘要翻译： 治疗哺乳动物身体中的细胞凋亡和/或坏死相关疾病，即放射线暴露障碍，化学暴露和摄入障碍，神经障碍和身体创伤障碍，并通过预处理来抵消它们的发作，通过从哺乳动物体内提取等分试样 血液，将提取的等分试样离体处理到氧化应激源，例如暴露于臭氧气体，温度应激器，即高于或低于体温的温度和紫外线，并将经处理的血液等分试样重新注射到哺乳动物体内。 这种治疗方法是减少身体凋亡/坏死的作用，并且更好地预处理身体，以抵御随后遇到的凋亡诱导事件。
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公开(公告)号：US20050181442A1
公开(公告)日：2005-08-18
申请号：US11108784
申请日：2005-04-19
摘要： This invention relates to a novel gene that shows tissue specific expression and increased expression in a low calcium concentration medium. Low renin hypertension is characterized by decreased levels of serum ionized calcium in the presence of increased levels of parathyroid hormone. It is hypothesized that hypertensive factor(s) are co-secreted with PTH in SHR, a model of low renin hypertension, the parathyroid hypertensive factor being one of them. As a negative calcium balance is present in spontaneously hypertensive rats (SHR), we searched for gene(s) involved in this dysregulation. A cDNA library was constructed from the SHR parathyroid gland which is a key regulator of serum ionized calcium. From 7 overlapping DNA fragments, a 1100-bp novel cDNA containing an open reading frame of 224 codons was reconstituted. This novel gene, named HCaRG (Hypertension-related, Calcium-regulated Gene), was negatively regulated by extracellular calcium concentration and its basal mRNA levels were higher in hypertensive animals. The deduced protein showed no transmembrane domain, 67% a helix content, a mutated calcium-binding site (EF-hand motif), 4 putative ‘leucine zipper’ motifs and a nuclear receptor-binding domain. At the subcellular level, HCaRG had a nuclear localization. We cloned the human homolog of this gene. Sequence comparison revealed 80% homology between rats and humans at the nucleotide and amino acid sequences. Tissue distribution showed a preponderance in the heart, stomach, jejunum, kidney (tubular fraction), liver and adrenal gland (mainly in the medulla). HCaRG mRNA was significantly more expressed in adult than in fetal organs, and its levels were decreased in tumors and cancerous cell lines. We observed that after 60-min ischemia followed by reperfusion, HCaRG mRNA declined rapidly in contrast with an increase in c-myc mRNA. Its levels then rose steadily to exceed baseline at 48 h of reperfusion. HEK293 cells stably transfected with HCaRG exhibited much lower proliferation, as shown by cell count and 3 H-thymidine incorporation. Taken together, our results suggest that HCaRG is a nuclear protein potentially involved in the control of cell proliferation.
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8.发明申请METHOD OF DETERMINING A PREDISPOSITION TO ATRIAL FIBRILLATION (AF) IN A SUBJECT 审中-公开确定受试者心房颤动（AF）预后的方法公开(公告)号：US20120065075A1
公开(公告)日：2012-03-15
申请号：US13176623
申请日：2011-07-05
申请人： Pavel Hamet , Johanne Tremblay , Jacques De Champlain , François de Champlain , Josée Beaudet , Bernard de Champlain , Réginald Nadeau , Pierre Larochelle , John Chalmers , Stephen Macmahon
发明人： Pavel Hamet , Johanne Tremblay , Jacques De Champlain , François de Champlain , Josée Beaudet , Bernard de Champlain , Réginald Nadeau , Pierre Larochelle , John Chalmers , Stephen Macmahon
CPC分类号： C12Q1/6883 , C12Q2600/106 , C12Q2600/156 , C12Q2600/172 , G01N33/6887 , G01N2333/58 , G01N2800/326
摘要： The present invention concerns a method of determining a predisposition to atrial fibrillation (AF) in a subject comprising: determining the presence of at least one copy of a risk allele from at least one polymorphic marker in a sample from the subject, wherein the presence of at least one copy of the risk allele is indicative of a predisposition to AF, and wherein said at least one polymorphic marker is: a) rs4674485; b) rs1466560; c) rs1880039; d) rs3849387; e) rs7039; f) rs2952860; g) rs9312515; h) rs1897527; i) rs2299277; j) rs2418828; k) rs2385833; l) rs6717960; m) rs10510266; or n) a substitute polymorphic marker in linkage disequilibrium with any one of the polymorphic markers of a) to m). Also described are kits for determining a predisposition to atrial fibrillation (AF).
摘要翻译： 本发明涉及确定受试者心房颤动（AF）倾向性的方法，其包括：确定来自受试者的样品中至少一个多态型标志物的风险等位基因的至少一个拷贝的存在，其中存在 风险等位基因的至少一个拷贝指示AF的倾向，并且其中所述至少一个多态性标记是：a）rs4674485; b）rs1466560; c）rs1880039; d）rs3849387; e）rs7039; f）rs2952860; g）rs9312515; h）rs1897527; i）rs2299277; j）rs2418828; k）rs2385833; l）rs6717960; m）rs10510266; 或n）与a）至m）中的任一个多态性标记连锁不平衡的替代多态性标记。 还描述了用于确定心房颤动（AF）倾向的试剂盒。
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9.发明申请Methods and compositions for characterizing patients for clinical outcome trials 审中-公开表征临床结果试验患者的方法和组成公开(公告)号：US20100136540A1
公开(公告)日：2010-06-03
申请号：US12457556
申请日：2009-06-15
申请人： Pavel Hamet , Johanne Tremblay , Ondrej Seda , Stephen Macmahon , John Chalmers
发明人： Pavel Hamet , Johanne Tremblay , Ondrej Seda , Stephen Macmahon , John Chalmers
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6883 , C12Q2600/106 , C12Q2600/156 , C12Q2600/172
摘要： The invention provides with methods for characterizing and selecting, within a population of subjects with type-2 diabetes, subjects that are suited for clinical trials based on the identification of one or more genetic features, which are single nucleotide polymorphisms (SNPs), short tandem repeats (STRs), and/or other genomic markers. The invention further involves characterizing these subjects based on the probability of developing complications related to type-2 diabetes, such as, myocardial infarction, stroke and albuminuria. Also described are combinations and kits for carrying out the above-described methods.
摘要翻译： 本发明提供了在基于识别一个或多个遗传特征的单体核苷酸多态性（SNP），短串联 重复（STR）和/或其他基因组标记。 本发明还涉及基于与2型糖尿病相关的并发症的可能性，例如心肌梗塞，中风和白蛋白尿来表征这些受试者。 还描述了用于实施上述方法的组合和试剂盒。
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10.发明申请METHODS, COMPOUNDS, AND COMPOSITIONS FOR TREATING METABOLIC DISORDERS AND DIABETES 审中-公开用于治疗代谢障碍和糖尿病的方法，化合物和组合物公开(公告)号：US20080262088A1
公开(公告)日：2008-10-23
申请号：US11963038
申请日：2007-12-21
申请人： Wendy HAUCK , Pavel Hamet
发明人： Wendy HAUCK , Pavel Hamet
IPC分类号： A61K31/10 , A61K31/155 , A61K31/64 , A61P3/00
CPC分类号： A61K31/10
摘要： Disclosed herein are methods, compounds and compositions for preventing or treating a pancreatic disorder, including diabetes mellitus (e.g. type 1 and/or type 2 diabetes). The invention generally includes administering to a subject 1,3-propanedisulfonic acid or a pharmaceutically acceptable salt thereof, e.g., 1,3-propanedisulfonic acid sodium salt. The invention also relates to methods, compounds and compositions for improving or at least stabilizing pancreatic function(s) and for the prevention and/or treatment of metabolic syndrome and its components. The invention further relates to methods, compounds and compositions for the prevention and/or treatment of dyslipidemia, and more particularly for reducing levels of harmful serum lipid levels, especially cholesterol and triglycerides in patients in need thereof, including diabetic patients.
摘要翻译： 本文公开了用于预防或治疗胰腺疾病，包括糖尿病（例如1型和/或2型糖尿病）的方法，化合物和组合物。 本发明通常包括向受试者施用1,3-丙二磺酸或其药学上可接受的盐，例如1,3-丙二磺酸钠盐。 本发明还涉及用于改善或至少稳定胰腺功能以及预防和/或治疗代谢综合征及其组分的方法，化合物和组合物。 本发明进一步涉及用于预防和/或治疗血脂异常的方法，化合物和组合物，更具体地涉及在需要的患者（包括糖尿病患者）中降低有害血清脂质水平，特别是胆固醇和甘油三酸酯的水平。
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