Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), is the most common form of hereditary colorectal cancer. Although great advances in the understanding of its molecular basis have taken...Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), is the most common form of hereditary colorectal cancer. Although great advances in the understanding of its molecular basis have taken place in the last decade, optimal selection of individuals for HNPCC genetic testing remains controversial. This is especially relevant since colonoscopy has been proven effective for reducing colorectal cancer incidence and mortality in individuals at-risk for this disorder. In this manuscript, we summarize the most significant contributions to this important issue that have appearedin the last few years.展开更多
Autosomal dominant polycystic kidney disease （ADPKD） is the most common inherited monogenic kidney disease. Characterized by the development and growth of cysts that cause progressive kidney enlargement, it ultimate...Autosomal dominant polycystic kidney disease （ADPKD） is the most common inherited monogenic kidney disease. Characterized by the development and growth of cysts that cause progressive kidney enlargement, it ultimately leads to end-stage renal disease. Approximately 85% of ADPKD cases are caused by mutations in the PKD1 gene, while mutations in the PKD2 gene account for the remaining 15% of cases. The PKD1 gene encodes for polycystin-1 （PC1）, a large multi-functional memb-rane receptor protein able to regulate ion channel complexes, whereas polycystin-2 （PC2）, encoded by the PKD2 gene, is an integral membrane protein that functions as a calcium-permeable cation channel, located mainly in the endoplasmic reticulum （ER）. In the primary cilia of the epithelial cells, PC1 interacts with PC2 to form a polycystin complex that acts as a mechanosensor, regulating signaling pathways involved in the differentiation of kidney tubular epithelial cells. Despite progress in understanding the function of these proteins, the molecular mechanisms associated with the pathogenesis of ADPKD remain unclear. In this review we discuss how an imbalance between functional PC1 and PC2 proteins may disrupt calcium channel activities in the cilium, plasma membrane and ER, thereby altering intracellular calcium signaling and leading to the aberrant cell proliferation and apoptosis associated with the development and growth of renal cysts. Research in this feld could lead to the discovery of new molecules able to rebalance intracellular calcium, thereby normalizing cell proliferation and reducing kidney cyst progression.展开更多
Autosomal dominant polycystic kidney disease （ADPKD）, the most frequent cause of genetic renal disease affecting approximately 4 to 7 million individuals worldwide and accounting for 7%-15% of patients on renal repl...Autosomal dominant polycystic kidney disease （ADPKD）, the most frequent cause of genetic renal disease affecting approximately 4 to 7 million individuals worldwide and accounting for 7%-15% of patients on renal replacement therapy, is a systemic disorder mainly involving the kidney but cysts can also occur in other organs such as the liver, pancreas, arachnoid membrane and seminal vesicles. Though computed tomography and magnetic resonance imaging （MRI） were similar in evaluating 81% of cystic lesions of the kidney, MRI may depict septa, wall thickening or enhancement leading to upgrade in cyst classification that can affect management. A screening strategy for intracranial aneurysms would provide 1.0 additional year of life without neurological disability to a 20-year-old patient with ADPKD and reduce the fnancial impact on society of the disease. Current treatment strategies include reducing： cyclic adenosine monophosphate levels, cell proliferation and fluid secretion. Several randomised clinical trials （RCT） including mammalian target of rapamycin inhibitors, somatostatin analoguesand a vasopressin V2 receptor antagonist have beenperformed to study the effect of diverse drugs ongrowth of renal and hepatic cysts, and on deteriorationof renal function. Prophylactic native nephrectomy isindicated in patients with a history of cyst infection orecurrent haemorrhage or to those in whom space musbe made to implant the graft. The absence of largeRCT on various aspects of the disease and its treatmen leaves considerable uncertainty and ambiguity in many aspects of ADPKD patient care as it relates to end stage renal disease （ESRD）. The outlook of patients with ADPKD is improving and is in fact much better than that for patients in ESRD due to other causes. This review highlights the need for well-structured RCTs as a frst step towards trying newer interventions so as to develop updated clinical management guidelines.展开更多
HEREDITARY angioedema （HAE） is an autosomal dominant inherited condition which was initially described by Osier in 1888.1 Patients with HAE can develop rapid subcutaneous or submucosal edema involving the hands, fee...HEREDITARY angioedema （HAE） is an autosomal dominant inherited condition which was initially described by Osier in 1888.1 Patients with HAE can develop rapid subcutaneous or submucosal edema involving the hands, feet, limbs, face, intestinal tract, even larynx and trachea. The mortality of an acute attack of HAE without treatment was reported as high as 30%.2 HAE is caused by the deficiency of Cl esterase inhibitor （CIINH） which results in episodes of edema in parts of the human body,展开更多
Medicinal use of spices/herbs has been gradually increased in the developed countries, Zingiber officinale （Ginger） is known to possess potent antioxidant and anti inflammatory properties. Therefore, the aim of this...Medicinal use of spices/herbs has been gradually increased in the developed countries, Zingiber officinale （Ginger） is known to possess potent antioxidant and anti inflammatory properties. Therefore, the aim of this study is to determine the possible anti-mutagenic effect of ginger against the genotoxic effect of anti-cancer drug Taxol 0.6 mg/kg. This study is conducted by using two types of cytogenetic studies in bone marrow cell of mal albino mice Mus musculus （average weight 25-30 g）. The animals were randomly distributed into six groups, each of 14 mi[ce, （GI） was given the solvent, （G2） treatment of the medical dose of Taxol drug, （G3） treatment of ginger, （G4） a pre-treatment of ginger prior to treatment of drug, （G5） a simultaneous treatment of ginger and treatment of drug, （G6） a post-treatment of ginger after treatment drug. The study results show that significant increase in total chromosomal aberrations and significant increase in the number of micronuclei were observed after treatment drug. The significant structural aberrations were in the form of end-to-end associations. The numerical chromosomal aberrations were endomitosis and polyploid. The results showed that the frequencies of chromosomal aberrations and micronuclei in ginger treated group were not significantly different from control. Simultaneous treatment of ginger was found to be effective in reducing the genotoxic effects induced by drug Taxol especially in the total number of the chromosomal aberrations and the number of micronuclei.展开更多
Gitelman's syndrome(GS) is a salt-losing tubulopathy with an autosomal recessive inheritance caused by mutations of SLC12A3, which encodes for the thiazidesensitive Na Cl cotransporter. In this study we report a n...Gitelman's syndrome(GS) is a salt-losing tubulopathy with an autosomal recessive inheritance caused by mutations of SLC12A3, which encodes for the thiazidesensitive Na Cl cotransporter. In this study we report a new mutation of SLC12A3 found in two brothers affected by GS. Hypokalemia, hypocalciuria and hyperreninemia were present in both patients while hypomagnesemia was detected only in one. Both patients are compound heterozygotes carrying one well known GS associated mutation(c.2581 C > T) and a new one(c.283 del C) in SLC12A3 gene. The new mutation results in a possible frame-shift with a premature stopcodon(pG ln95 Argfs X19). The parents of the patients, heterozygous carriers of the mutations found in SLC12A3, have no disease associated phenotype. Therefore, the new mutation is causative of GS.展开更多
Despite the acceptance of physical activity （PA） being integral to a young person＇s health, children with disability often exhibit low levels of PA. In young people with cystic fibrosis （CF） the importance of exe...Despite the acceptance of physical activity （PA） being integral to a young person＇s health, children with disability often exhibit low levels of PA. In young people with cystic fibrosis （CF） the importance of exercise and daily PA is acknowledged by clinicians and their support teams, however, there is a lack of knowledge related to its prescription. CF is a recessive genetic disorder affecting the lung, pancreas and sweat glands. CF is the most common life shortening genetic disease in the Caucasian population for which there is no cure. In the UK, CF affects over 9000 people, with 4000 under 16 years of age. Only about half of the CF population can expect to live beyond 40 years of age. Besides drug therapies, rehabilitative exercise programmes form an important component of treatment and long term exercise programmes are considered positive treatment strategies, but all lack any detailed prescriptive information. Several reviews and editorials have highlighted the lack of evidence based research in PA and exercise training in young people with CF; but advocate a greater need for understanding the role of exercise in therapeutic interventions. The purpose of this review is to update the reader on the current recommendations and evidence in PA and exercise training for young people with CE These developments have extended our understanding of PA and exercise training in children and adolescents with CF, and its implementation in the management of this chronic disease.展开更多
基金Ministerio de Educación y Ciencia (SAF 04-07190 and 07/-64873) from the Asociación Espaola contra el Cáncer, the Hospital Clínic and Fondo de Investigación Sanitaria
文摘Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), is the most common form of hereditary colorectal cancer. Although great advances in the understanding of its molecular basis have taken place in the last decade, optimal selection of individuals for HNPCC genetic testing remains controversial. This is especially relevant since colonoscopy has been proven effective for reducing colorectal cancer incidence and mortality in individuals at-risk for this disorder. In this manuscript, we summarize the most significant contributions to this important issue that have appearedin the last few years.
基金Supported by University of Ferrara local funds:FAR 2012,2013,2014 and Regione Emilia Romagna grant(Ricerca Regione-Università)2007-2009
文摘Autosomal dominant polycystic kidney disease （ADPKD） is the most common inherited monogenic kidney disease. Characterized by the development and growth of cysts that cause progressive kidney enlargement, it ultimately leads to end-stage renal disease. Approximately 85% of ADPKD cases are caused by mutations in the PKD1 gene, while mutations in the PKD2 gene account for the remaining 15% of cases. The PKD1 gene encodes for polycystin-1 （PC1）, a large multi-functional memb-rane receptor protein able to regulate ion channel complexes, whereas polycystin-2 （PC2）, encoded by the PKD2 gene, is an integral membrane protein that functions as a calcium-permeable cation channel, located mainly in the endoplasmic reticulum （ER）. In the primary cilia of the epithelial cells, PC1 interacts with PC2 to form a polycystin complex that acts as a mechanosensor, regulating signaling pathways involved in the differentiation of kidney tubular epithelial cells. Despite progress in understanding the function of these proteins, the molecular mechanisms associated with the pathogenesis of ADPKD remain unclear. In this review we discuss how an imbalance between functional PC1 and PC2 proteins may disrupt calcium channel activities in the cilium, plasma membrane and ER, thereby altering intracellular calcium signaling and leading to the aberrant cell proliferation and apoptosis associated with the development and growth of renal cysts. Research in this feld could lead to the discovery of new molecules able to rebalance intracellular calcium, thereby normalizing cell proliferation and reducing kidney cyst progression.
文摘Autosomal dominant polycystic kidney disease （ADPKD）, the most frequent cause of genetic renal disease affecting approximately 4 to 7 million individuals worldwide and accounting for 7%-15% of patients on renal replacement therapy, is a systemic disorder mainly involving the kidney but cysts can also occur in other organs such as the liver, pancreas, arachnoid membrane and seminal vesicles. Though computed tomography and magnetic resonance imaging （MRI） were similar in evaluating 81% of cystic lesions of the kidney, MRI may depict septa, wall thickening or enhancement leading to upgrade in cyst classification that can affect management. A screening strategy for intracranial aneurysms would provide 1.0 additional year of life without neurological disability to a 20-year-old patient with ADPKD and reduce the fnancial impact on society of the disease. Current treatment strategies include reducing： cyclic adenosine monophosphate levels, cell proliferation and fluid secretion. Several randomised clinical trials （RCT） including mammalian target of rapamycin inhibitors, somatostatin analoguesand a vasopressin V2 receptor antagonist have beenperformed to study the effect of diverse drugs ongrowth of renal and hepatic cysts, and on deteriorationof renal function. Prophylactic native nephrectomy isindicated in patients with a history of cyst infection orecurrent haemorrhage or to those in whom space musbe made to implant the graft. The absence of largeRCT on various aspects of the disease and its treatmen leaves considerable uncertainty and ambiguity in many aspects of ADPKD patient care as it relates to end stage renal disease （ESRD）. The outlook of patients with ADPKD is improving and is in fact much better than that for patients in ESRD due to other causes. This review highlights the need for well-structured RCTs as a frst step towards trying newer interventions so as to develop updated clinical management guidelines.
文摘HEREDITARY angioedema （HAE） is an autosomal dominant inherited condition which was initially described by Osier in 1888.1 Patients with HAE can develop rapid subcutaneous or submucosal edema involving the hands, feet, limbs, face, intestinal tract, even larynx and trachea. The mortality of an acute attack of HAE without treatment was reported as high as 30%.2 HAE is caused by the deficiency of Cl esterase inhibitor （CIINH） which results in episodes of edema in parts of the human body,
文摘Medicinal use of spices/herbs has been gradually increased in the developed countries, Zingiber officinale （Ginger） is known to possess potent antioxidant and anti inflammatory properties. Therefore, the aim of this study is to determine the possible anti-mutagenic effect of ginger against the genotoxic effect of anti-cancer drug Taxol 0.6 mg/kg. This study is conducted by using two types of cytogenetic studies in bone marrow cell of mal albino mice Mus musculus （average weight 25-30 g）. The animals were randomly distributed into six groups, each of 14 mi[ce, （GI） was given the solvent, （G2） treatment of the medical dose of Taxol drug, （G3） treatment of ginger, （G4） a pre-treatment of ginger prior to treatment of drug, （G5） a simultaneous treatment of ginger and treatment of drug, （G6） a post-treatment of ginger after treatment drug. The study results show that significant increase in total chromosomal aberrations and significant increase in the number of micronuclei were observed after treatment drug. The significant structural aberrations were in the form of end-to-end associations. The numerical chromosomal aberrations were endomitosis and polyploid. The results showed that the frequencies of chromosomal aberrations and micronuclei in ginger treated group were not significantly different from control. Simultaneous treatment of ginger was found to be effective in reducing the genotoxic effects induced by drug Taxol especially in the total number of the chromosomal aberrations and the number of micronuclei.
文摘Gitelman's syndrome(GS) is a salt-losing tubulopathy with an autosomal recessive inheritance caused by mutations of SLC12A3, which encodes for the thiazidesensitive Na Cl cotransporter. In this study we report a new mutation of SLC12A3 found in two brothers affected by GS. Hypokalemia, hypocalciuria and hyperreninemia were present in both patients while hypomagnesemia was detected only in one. Both patients are compound heterozygotes carrying one well known GS associated mutation(c.2581 C > T) and a new one(c.283 del C) in SLC12A3 gene. The new mutation results in a possible frame-shift with a premature stopcodon(pG ln95 Argfs X19). The parents of the patients, heterozygous carriers of the mutations found in SLC12A3, have no disease associated phenotype. Therefore, the new mutation is causative of GS.
文摘Despite the acceptance of physical activity （PA） being integral to a young person＇s health, children with disability often exhibit low levels of PA. In young people with cystic fibrosis （CF） the importance of exercise and daily PA is acknowledged by clinicians and their support teams, however, there is a lack of knowledge related to its prescription. CF is a recessive genetic disorder affecting the lung, pancreas and sweat glands. CF is the most common life shortening genetic disease in the Caucasian population for which there is no cure. In the UK, CF affects over 9000 people, with 4000 under 16 years of age. Only about half of the CF population can expect to live beyond 40 years of age. Besides drug therapies, rehabilitative exercise programmes form an important component of treatment and long term exercise programmes are considered positive treatment strategies, but all lack any detailed prescriptive information. Several reviews and editorials have highlighted the lack of evidence based research in PA and exercise training in young people with CF; but advocate a greater need for understanding the role of exercise in therapeutic interventions. The purpose of this review is to update the reader on the current recommendations and evidence in PA and exercise training for young people with CE These developments have extended our understanding of PA and exercise training in children and adolescents with CF, and its implementation in the management of this chronic disease.
