Amanita phalloides intoxication: mechanism of toxicity, clinical manifestations and therapeutic approaches

Poisoning due to mushroom ingestion is a relatively rare but deadly cause of acute liver failure (ALF). Consumption of the poisonous mushroom Amanita phalloides, also known as ‘death cap’, is one of the most common causes of mushroom poisoning worldwide, being involved in the majority of human fatalities caused due to mushroom ingestion. A major portion of the liver damage due to Amanita phalloides is related to powerful toxins known as amanitins, which cause impairment in protein synthesis and subsequent cell necrosis by the inhibition of RNA polymerase II. Initially the presentation is that of an asymptomatic lag phase, followed by gastrointestinal symptoms and hepato-renal involvement. Amatoxin poisoning may progress into fulminant hepatic failure and eventually death if liver transplantation is not performed. It is based on a careful assessment of history of type and duration of mushroom ingestion, as well as the clinical manifestations. Diagnosis can be confirmed by laboratory tests measuring urinary amatoxin levels and identification of the mushroom. Although N-Acetyl Cysteine and Penicillin-G have proven to be effective therapeutic agents, Orthotopic Liver Transplantation (OLT) or Auxiliary Partial Orthotopic Liver Transplantation (APOLT) is the only treatment option for most of the cases carrying a poor prognosis.

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Chemokines as Therapeutic Targets in Cardiovascular Disease

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.118.312037 ◽

2019 ◽

Vol 39 (4) ◽

pp. 583-592 ◽

Cited By ~ 14

Author(s):

Heidi Noels ◽

Christian Weber ◽

Rory R. Koenen

Keyword(s):

Cardiovascular Disease ◽

Clinical Manifestations ◽

Therapeutic Targets ◽

Drug Approval ◽

Atherosclerotic Cardiovascular Disease ◽

Therapeutic Approaches ◽

The Road ◽

Recent Developments ◽

The Cantos ◽

Underlying Inflammation

With the incidence and impact of atherosclerotic cardiovascular disease and its clinical manifestations still rising, therapeutic options that target the causal mechanisms of this disorder are highly desired. Since the CANTOS trial (Canakinumab Antiinflammatory Thrombosis Outcome Study) has demonstrated that lowering inflammation can be beneficial, focusing on mechanisms underlying inflammation, for example, leukocyte recruitment, is feasible. Being key orchestrators of leukocyte trafficking, chemokines have not lost their attractiveness as therapeutic targets, despite the difficult road to drug approval thus far. Still, innovative therapeutic approaches are being developed, paving the road towards the first chemokine-based therapeutic against inflammation. In this overview, recent developments for chemokines and for the chemokine-like factor MIF (macrophage migration inhibitory factor) will be discussed.

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A Yeast-Based Model for Hereditary Motor and Sensory Neuropathies: A Simple System for Complex, Heterogeneous Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms21124277 ◽

2020 ◽

Vol 21 (12) ◽

pp. 4277 ◽

Cited By ~ 1

Author(s):

Weronika Rzepnikowska ◽

Joanna Kaminska ◽

Dagmara Kabzińska ◽

Katarzyna Binięda ◽

Andrzej Kochański

Keyword(s):

Molecular Mechanisms ◽

Genetic Diagnosis ◽

Clinical Manifestations ◽

Model System ◽

Research Field ◽

Therapeutic Approaches ◽

Rare Disorders ◽

Advantages And Disadvantages ◽

Pathogenic Variants ◽

Disease Subtypes

Charcot–Marie–Tooth (CMT) disease encompasses a group of rare disorders that are characterized by similar clinical manifestations and a high genetic heterogeneity. Such excessive diversity presents many problems. Firstly, it makes a proper genetic diagnosis much more difficult and, even when using the most advanced tools, does not guarantee that the cause of the disease will be revealed. Secondly, the molecular mechanisms underlying the observed symptoms are extremely diverse and are probably different for most of the disease subtypes. Finally, there is no possibility of finding one efficient cure for all, or even the majority of CMT diseases. Every subtype of CMT needs an individual approach backed up by its own research field. Thus, it is little surprise that our knowledge of CMT disease as a whole is selective and therapeutic approaches are limited. There is an urgent need to develop new CMT models to fill the gaps. In this review, we discuss the advantages and disadvantages of yeast as a model system in which to study CMT diseases. We show how this single-cell organism may be used to discriminate between pathogenic variants, to uncover the mechanism of pathogenesis, and to discover new therapies for CMT disease.

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Uncovering the Neuroprotective Mechanisms of Curcumin on Transthyretin Amyloidosis

International Journal of Molecular Sciences ◽

10.3390/ijms20061287 ◽

2019 ◽

Vol 20 (6) ◽

pp. 1287 ◽

Cited By ~ 5

Author(s):

Nelson Ferreira ◽

Maria Saraiva ◽

Maria Almeida

Keyword(s):

Immune System ◽

Amino Acid ◽

Molecular Mechanisms ◽

Clinical Manifestations ◽

Current Work ◽

Amino Acid Substitutions ◽

Therapeutic Approaches ◽

Transthyretin Amyloidosis ◽

Chemical Chaperones ◽

Attr Amyloidosis

Transthyretin (TTR) amyloidoses (ATTR amyloidosis) are diseases associated with transthyretin (TTR) misfolding, aggregation and extracellular deposition in tissues as amyloid. Clinical manifestations of the disease are variable and include mainly polyneuropathy and/or cardiomyopathy. The reasons why TTR forms aggregates and amyloid are related with amino acid substitutions in the protein due to mutations, or with environmental alterations associated with aging, that make the protein more unstable and prone to aggregation. According to this model, several therapeutic approaches have been proposed for the diseases that range from stabilization of TTR, using chemical chaperones, to clearance of the aggregated protein deposited in tissues in the form of oligomers or small aggregates, by the action of disruptors or by activation of the immune system. Interestingly, different studies revealed that curcumin presents anti-amyloid properties, targeting multiple steps in the ATTR amyloidogenic cascade. The effects of curcumin on ATTR amyloidosis will be reviewed and discussed in the current work in order to contribute to knowledge of the molecular mechanisms involved in TTR amyloidosis and propose more efficient drugs for therapy.

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The onset of psoriasis during the treatment of inflammatory bowel diseases with infliximab: should biological therapy be suspended?

Arquivos de Gastroenterologia ◽

10.1590/s0004-28032012000200014 ◽

2012 ◽

Vol 49 (2) ◽

pp. 172-176 ◽

Cited By ~ 12

Author(s):

Rafael Denadai ◽

Fábio Vieira Teixeira ◽

Rogério Saad-Hossne

Keyword(s):

Clinical Manifestations ◽

Infliximab Therapy ◽

Inclusion Criteria ◽

Therapeutic Approaches ◽

Plaque Type ◽

Bowel Diseases ◽

History Of ◽

Cutaneous Reactions ◽

Inflammatory Bowel ◽

Psoriatic Lesions

CONTEXT: Several paradoxical cases of infliximab-induced or-exacerbated psoriatic lesions have been described in the recent years. There is disagreement regarding the need to discontinue infliximab in order to achieve the resolution of these adverse cutaneous reactions specifically in inflammatory bowel disease (IBD) patients. OBJECTIVE: To systematically review the literature to collect information on IBD patients that showed this adverse cutaneous reaction, focusing mainly on the therapeutic approach. METHODS: A systematic literature review was performed utilizing Medline, Embase, SciELO and Lilacs databases. Published studies were identified, reviewed and the data were extracted. RESULTS: Thirty-four studies (69 IBD patients) met inclusion criteria for review. There was inconsistency in reporting of some clinical and therapeutic aspects. Most patients included had Crohn's disease (89.86%), was female (47.83%), had an average age of 27.11 years, and no reported history of psoriasis (84.05%). The patients developed primarily plaque-type psoriasis (40.58%). There was complete remission of psoriatic lesions in 86.96% of IBD patients, existing differences in the therapeutic approaches; cessation of infliximab therapy led to resolution in 47.83% of cases and 43.48% of patients were able to continue infliximab therapy. CONCLUSION: As increasing numbers of IBD patients with psoriasis induced or exacerbated by infliximab, physicians should be aware of its clinical manifestations so that appropriate diagnosis and treatment are properly established. The decision whether to continue or discontinue infliximab should be individualized.

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The Antiphospholipid Syndrome

Hematology ◽

10.1182/asheducation-2007.1.136 ◽

2007 ◽

Vol 2007 (1) ◽

pp. 136-142 ◽

Cited By ~ 15

Author(s):

Jacob H. Rand

Keyword(s):

Antiphospholipid Syndrome ◽

Pregnancy Complications ◽

Binding Proteins ◽

Clinical Manifestations ◽

Therapeutic Approaches ◽

Vascular Thrombosis ◽

Phospholipid Binding ◽

Thrombophilic Condition

Abstract The antiphospholipid syndrome (APS) is an autoimmune thrombophilic condition that is marked by the presence of antibodies that recognize phospholipid-binding proteins. The clinical manifestations of APS include vascular thrombosis and pregnancy complications, especially recurrent spontaneous miscarriages. This article provides an update on diagnostic and therapeutic approaches to this disorder.

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Oral pemphigus vulgaris

Journal of Kathmandu Medical College ◽

10.3126/jkmc.v4i3.18239 ◽

2017 ◽

Vol 4 (3) ◽

pp. 100-103

Author(s):

Mohit Sharma

Keyword(s):

Clinical Manifestations ◽

Pemphigus Vulgaris ◽

Oral Literature ◽

Therapeutic Approaches ◽

The Past ◽

Mucosal Surfaces ◽

Life Threatening ◽

Delays In Diagnosis ◽

Oral Involvement ◽

Dental Professionals

Pemphigus is a group of potentially life-threatening autoimmune mucocutaneous diseases characterized by epithelial blistering affecting cutaneous and/ or mucosal surfaces. Pemphigus affects 0.1-0.5 patients per 100,000 population per year. Oral lesions of pemphigus are seen in up to 18% of patients at dermatology out-patient clinics, but despite the frequency of oral involvement, and novel therapeutic approaches, there are surprisingly few recent studies of either the oral manifestations of pemphigus or their management, and delays in diagnosis are still common. Most patients are initially misdiagnosed and improperly treated for many months or even years. Dental professionals must be sufficiently familiar with the clinical manifestations of pemphigus vulgaris to ensure early diagnosis and treatment, since this in turn determines the prognosis and course of the disease. Pemphigus has been reviewed in the oral literature in the past decade, but several advances in the understanding of the etiopathogenesis, pemphigus variants, and management warrant an update. Here, we report a case of pemphigus vulgaris that was misdiagnosed in its earliest stage. Oral ulceration may arise from a variety of causes. This case illustrates that, although rare, pemphigus vulgaris may need to be included in differential diagnosis.

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Thoracic involvement in generalised lymphatic anomaly (or lymphangiomatosis)

European Respiratory Review ◽

10.1183/16000617.0018-2016 ◽

2016 ◽

Vol 25 (140) ◽

pp. 170-177 ◽

Cited By ~ 14

Author(s):

Francesca Luisi ◽

Olga Torre ◽

Sergio Harari

Keyword(s):

Clinical Trials ◽

Rare Disease ◽

Congenital Abnormalities ◽

Wide Spectrum ◽

Case Reports ◽

Clinical Manifestations ◽

Organ Involvement ◽

Therapeutic Approaches ◽

Lymphatic Development ◽

Single Organ

Generalised lymphatic anomaly (GLA), also known as lymphangiomatosis, is a rare disease caused by congenital abnormalities of lymphatic development. It usually presents in childhood but can also be diagnosed in adults. GLA encompasses a wide spectrum of clinical manifestations ranging from single-organ involvement to generalised disease. Given the rarity of the disease, most of the information regarding it comes from case reports. To date, no clinical trials concerning treatment are available. This review focuses on thoracic GLA and summarises possible diagnostic and therapeutic approaches.

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Management of Hepatic Encephalopathy by Traditional Chinese Medicine

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/835686 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Chun Yao ◽

Nong Tang ◽

Guoxiang Xie ◽

Xiaojiao Zheng ◽

Ping Liu ◽

...

Keyword(s):

Nervous System ◽

Hepatic Encephalopathy ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Liver Dysfunction ◽

Clinical Manifestations ◽

Modern Medicine ◽

Future Perspective ◽

Therapeutic Approaches ◽

Complex Mechanisms

In spite of the impressive progress in the investigation of hepatic encephalopathy (HE), the complex mechanisms underlying the onset and deterioration of HE are still not fully understood. Currently, none of the existing theories provide conclusive explanations on the symptoms that link liver dysfunction to nervous system disorders and clinical manifestations. This paper summarized the diagnostic and therapeutic approaches used for HE in modern medicine and traditional Chinese medicine and provided future perspective in HE therapies from the viewpoint of holistic and personalized Chinese medicine.

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A chronic animal model of migraine, induced by repeated meningeal nociception, characterized by a behavioral and pharmacological approach

Cephalalgia ◽

10.1177/0333102413486320 ◽

2013 ◽

Vol 33 (13) ◽

pp. 1096-1105 ◽

Cited By ~ 60

Author(s):

Agustin Melo-Carrillo ◽

Alberto Lopez-Avila

Keyword(s):

Animal Model ◽

Clinical Manifestations ◽

Neural Mechanisms ◽

Therapeutic Approaches ◽

Grooming Behavior ◽

Principal Characteristics ◽

Unilateral Headache ◽

Meningeal Nociception ◽

Resting Behavior ◽

Novel Therapeutic

Background Migraine is a chronic neurovascular disease characterized by recurrent unilateral headache, which induces incapacity. Despite all the progress that migraine research has provided, the neural mechanisms underlying the onset and maintenance of migraine attacks are poorly understood. Due to the complex characteristics of the disorder, it is difficult to develop a proper animal model that mimics all the clinical manifestations in humans. Objective Taking into account the principal characteristics of the disease, the aim of this study is to develop a chronic animal model of migraine in which we can reproduce behavioral and pharmacological phenomena similar to those displayed by migraineurs. Results Our animal model displayed behavioral and pharmacological results similar to those experienced by migraineurs. Specifically, there was a decrease in routine physical activity and an increase in resting behavior. Also, the animals exhibited a novel behavior that we called ipsilateral facial grooming behavior provoked by the meningeal nociception. Moreover, one of the drugs used as treatment for migraine reduced the manifestations previously described. Our results determine that the model mimics many of the clinical features that patients exhibit during migraine attacks. This model can contribute to further understanding of the pathophysiology and the study of novel therapeutic approaches.

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