scholarly journals Review of Pharmacological Strategies with Repurposed Drugs for Hereditary Hemorrhagic Telangiectasia Related Bleeding

2020 ◽  
Vol 9 (6) ◽  
pp. 1766 ◽  
Author(s):  
Virginia Albiñana ◽  
Angel M. Cuesta ◽  
Isabel de Rojas-P ◽  
Eunate Gallardo-Vara ◽  
Lucía Recio-Poveda ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Hereditary Hemorrhagic Telangiectasia ◽  
Arteriovenous Malformations ◽  
Blood Transfusions ◽  
Ground Zero ◽  
Internal Organs ◽  
Antifibrinolytic Agents ◽  
Estrogen Receptor Modulators ◽  
Repurposed Drugs ◽  
Receptor Modulators

The diagnosis of hereditary hemorrhagic telangiectasia (HHT) is based on the Curaçao criteria: epistaxis, telangiectases, arteriovenous malformations in internal organs, and family history. Genetically speaking, more than 90% of HHT patients show mutations in ENG or ACVRL1/ALK1 genes, both belonging to the TGF-β/BMP9 signaling pathway. Despite clear knowledge of the symptoms and genes of the disease, we still lack a definite cure for HHT, having just palliative measures and pharmacological trials. Among the former, two strategies are: intervention at “ground zero” to minimize by iron and blood transfusions in order to counteract anemia. Among the later, along the last 15 years, three different strategies have been tested: (1) To favor coagulation with antifibrinolytic agents (tranexamic acid); (2) to increase transcription of ENG and ALK1 with specific estrogen-receptor modulators (bazedoxifene or raloxifene), antioxidants (N-acetylcysteine, resveratrol), or immunosuppressants (tacrolimus); and (3) to impair the abnormal angiogenic process with antibodies (bevacizumab) or blocking drugs like etamsylate, and propranolol. This manuscript reviews the main strategies and sums up the clinical trials developed with drugs alleviating HHT.

Origination Progress and Utility of Selective Estrogen Receptor Modulators in Clinical Practice as an Efficient Substitute of Estrogen for Treating Hormone Dependent Issues

2019 ◽  
Vol 4 (3) ◽  
pp. 200-208
Author(s):  
A. Kulshrestha ◽  
J. Pandey
Keyword(s):  
Clinical Trials ◽  
Estrogen Receptor ◽  
Selective Estrogen Receptor Modulators ◽  
Specific Reference ◽  
Estrogen Receptor Modulators ◽  
Albright Syndrome ◽  
Cyclical Mastalgia ◽  
Post Menopausal ◽  
Receptor Modulators ◽  
Menopausal Depression

The discovery, development and utility of selective estrogen receptor modulators (SERMs) are presented in this study. As per literature review SERMs used in the treatment of estrogen hormone responsive diseases like osteoporosis, Alzheimer, angiogenesis, hyperlipidemia, coronary heart disease, atherosclerosis, endometriosis, breast cancer, post-menopausal depression, dysfunctional uterine bleeding, gynacomastia, Albright syndrome, ovarian cancer, dyspareunia, cyclical mastalgia, hypogondism and induced ovulation in sub-fertile woman, etc. Basically world wide a large no. compounds available those function as SERMs successfully or under different phase clinical trials or discontinued because of unwanted side effects during clinical trials. This work describes the specific reference compounds which have created a substitute of estrogen for treating hormone dependent issues.

The Role of Selective Estrogen Receptor Modulators in the Prevention of Breast Cancer: Comparison of the Clinical Trials

2004 ◽  
Vol 9 (2) ◽  
pp. 116-125 ◽  
Author(s):  
Silvana Martino ◽  
Joseph Costantino ◽  
Michelle McNabb ◽  
John Mershon ◽  
Katherine Bryant ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Estrogen Receptor ◽  
Selective Estrogen Receptor Modulators ◽  
Estrogen Receptor Modulators ◽  
Receptor Modulators ◽  
Prevention Of Breast Cancer

scholarly journals Genetic testing for hereditary hemorrhagic telangiectasia

2018 ◽  
Vol 2 (s1) ◽  
pp. 32-34
Author(s):  
Yeltay Rakhmanov ◽  
Paolo Enrico Maltese ◽  
Stefano Paolacci ◽  
Carla Marinelli ◽  
Raul Ettore Mattassi ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Clinical Trials ◽  
Differential Diagnosis ◽  
Hereditary Hemorrhagic Telangiectasia ◽  
Arteriovenous Malformations ◽  
Autosomal Dominant ◽  
De Novo ◽  
Incomplete Penetrance ◽  
Gene Test ◽  
Vascular Dysplasia

Abstract Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia characterized by telangiectases and arteriovenous malformations. These lesions cause bleeding, particularly in the nose, gastrointestinal tract and brain. HHT has incomplete penetrance, variable expressivity and genetic heterogeneity. De novo mutations associated with the onset of sporadic HHT have been reported. This Utility Gene Test was prepared on the basis of an analysis of the literature and existing diagnostic protocols. It is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials.

scholarly journals Potential Second-Hits in Hereditary Hemorrhagic Telangiectasia

2020 ◽  
Vol 9 (11) ◽  
pp. 3571
Author(s):  
Carmelo Bernabeu ◽  
Pinar Bayrak-Toydemir ◽  
Jamie McDonald ◽  
Michelle Letarte
Keyword(s):  
Hereditary Hemorrhagic Telangiectasia ◽  
Arteriovenous Malformations ◽  
Somatic Mutations ◽  
Autosomal Dominant ◽  
Genetic Disorder ◽  
Vascular Lesions ◽  
Mechanical Trauma ◽  
Internal Organs ◽  
Second Hit ◽  
Functional Mechanisms

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disorder that presents with telangiectases in skin and mucosae, and arteriovenous malformations (AVMs) in internal organs such as lungs, liver, and brain. Mutations in ENG (endoglin), ACVRL1 (ALK1), and MADH4 (Smad4) genes account for over 95% of HHT. Localized telangiectases and AVMs are present in different organs, with frequencies which differ among affected individuals. By itself, HHT gene heterozygosity does not account for the focal nature and varying presentation of the vascular lesions leading to the hypothesis of a “second-hit” that triggers the lesions. Accumulating research has identified a variety of triggers that may synergize with HHT gene heterozygosity to generate the vascular lesions. Among the postulated second-hits are: mechanical trauma, light, inflammation, vascular injury, angiogenic stimuli, shear stress, modifier genes, and somatic mutations in the wildtype HHT gene allele. The aim of this review is to summarize these triggers, as well as the functional mechanisms involved.

Menopause and psychosis

2016 ◽  
Vol 33 (S1) ◽  
pp. S46-S46
Author(s):  
J. Usall ◽  
E. Huerta-Ramos
Keyword(s):  
Clinical Trials ◽  
Postmenopausal Women ◽  
Negative Symptoms ◽  
Late Onset ◽  
Preventive Treatment ◽  
Estrogen Receptor Modulators ◽  
Competing Interest ◽  
Receptor Modulators ◽  
Better Than

There has been little research into the effects of menopause on symptoms, social and cognitive functioning in women with schizophrenia, and the results are controversial. The most replicated finding is that late-onset schizophrenia is more prevalent in women than in men and that this fact appears to be related to the diminution of estrogen levels during menopause.Estrogens have a known protective effect on CNS. Animal research has shown that estrogen has a modulating effect on the dopaminergic, glutamatergic and serotonergic systems.There are concerns about long-term use of sexual hormone therapy in postmenopausal women with regard to breast cancer risk, and the use of the selective estrogen receptor modulators (SERMS's) can be a better option.Raloxifene is a SERM that is used in the preventive treatment of postmenopausal osteoporosis and has no effect in the breast and uterus. A number of studies seem to indicate that raloxifene acts on brain dopamine and serotonin systems in a similar way to conjugated estrogens.In this presentation, I will show the results of some clinical trials that have studied the efficacy of raloxifene as a coadjuvant treatment of patients with schizophrenia. Our team has done two clinical trials that studied the efficacy of 60 mg of raloxifene for the treatment of negative symptoms in postmenopausal women with schizophrenia. Our results showed that raloxifene improved the negative symptoms better than placebo. We concluded that raloxifene seems to be a promising option to treat some patients with schizophrenia.Disclosure of interestThe authors have not supplied their declaration of competing interest.

A Review of the Prevention of Invasive Breast Cancer with Raloxifene in Postmenopausal Women

2009 ◽  
Vol 1 ◽  
pp. CMT.S2063
Author(s):  
Belisario A. Arango ◽  
Aurelio B. Castrellon ◽  
Edgardo S. Santos ◽  
Stefan Gluck
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Postmenopausal Women ◽  
Invasive Breast Cancer ◽  
The United States ◽  
Estrogen Receptor Modulators ◽  
Significant Difference ◽  
Prevention Of Osteoporosis ◽  
Receptor Modulators ◽  
Star Trial

Breast cancer remains the second leading cause of malignancy-related death in women in the United States, regardless of advances in novel therapeutic agents. High priority should be emphasized in research aimed at the study of pharmacological and natural compounds that may potentially prevent the development of breast cancer in susceptible patients. Among the known selective estrogen receptor modulators with proven chemopreventive effects, raloxifene has been studied in a number of clinical trials evaluating this drug for the prevention of osteoporosis and coronary heart disease. The MORE and CORE trials had as a primary end point the efficacy of raloxifene in the treatment of women with osteoporosis. These studies showed that raloxifene reduced the risk of invasive breast cancer in postmenopausal women. However, the STAR trial showed no significant difference between raloxifene and tamoxifen recipients in the incidence of invasive breast cancer in postmenopausal women at high risk of invasive breast cancer. This review focuses on the chemopreventive properties of raloxifene and the clinical trials that have proven its efficacy as a chemopreventive agent in invasive breast cancer.

scholarly journals Hereditary Hemorrhagic Telangiectasia or Osler-Weber -Rendu Syndrome: Management of Epistaxis in 4 Cases

2020 ◽  
Vol 17 (2) ◽  
Author(s):  
Salina H ◽  
Lim PS ◽  
Gendeh BS
Keyword(s):  
Hereditary Hemorrhagic Telangiectasia ◽  
Arteriovenous Malformations ◽  
Autosomal Dominant ◽  
Hospital Admissions ◽  
Blood Transfusions ◽  
Vascular Structure ◽  
Autosomal Dominant Disorder ◽  
Common Presentation ◽  
Severe Epistaxis ◽  
The Common

Hereditary Hemorrhagic Telangiectasia, also known as Osler-Weber-Rendu Syndrome is an autosomal dominant disorder causing systemic abnormalities of the vascular structure. There are multiple arteriovenous malformations present in the skin and mucosal surface of the nail beds, nose, gastrointestinal tract, lungs and brain. Epistaxis is the common presentation symptom, which may require multiple hospital admissions and blood transfusions. It is extremely rare disease in our population. We report 4 cases of HHT who presented to us with moderate to severe epistaxis and how we managed these patients.

Sign in / Sign up

Export Citation Format

Share Document