Faculty Opinions recommendation of Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities.

Author(s):  
Helmy Siragy
Nature ◽  
2012 ◽  
Vol 482 (7383) ◽  
pp. 98-102 ◽  
Author(s):  
Lynn M. Boyden ◽  
Murim Choi ◽  
Keith A. Choate ◽  
Carol J. Nelson-Williams ◽  
Anita Farhi ◽  
...  

2018 ◽  
Author(s):  
Isadora Cavalcante ◽  
Eric Clauser ◽  
Anna Vaczlavik ◽  
Ludivine Drougat ◽  
Claudimara Lotfi ◽  
...  

2020 ◽  
Vol 23 (8) ◽  
pp. 814-826
Author(s):  
Pradeep Hanumanthappa ◽  
Arpitha Ashok ◽  
Inderjit Prakash ◽  
Carmel I. Priya ◽  
Julie Zinzala ◽  
...  

Background: Parkinson’s disease ranks second, after Alzheimer’s as the major neurodegenerative disorder, for which no cure or disease-modifying therapies exist. Ample evidence indicate that PD manifests as a result of impaired anti-oxidative machinery leading to neuronal death wherein Cullin-3 has ascended as a potential therapeutic target for diseases involving damaged anti-oxidative machinery. Objective: The design of target specific inhibitors for the Cullin-3 protein might be a promising strategy to increase the Nrf2 levels and to decrease the possibility of “off-target” toxic properties. Methods: In the present study, an integrated computational and wet lab approach was adopted to identify small molecule inhibitors for Cullin-3. The rational drug designing process comprised homology modeling and derivation of the pharmacophore for Cullin-3, virtual screening of Zinc natural compound database, molecular docking and Molecular dynamics based screening of ligand molecules. In vivo validations of an identified lead compound were conducted in the PD model of C. elegans. Results and Discussion: Our strategy yielded a potential inhibitor; (Glide score = -12.31), which was evaluated for its neuroprotective efficacy in the PD model of C. elegans. The inhibitor was able to efficiently defend against neuronal death in PD model of C. elegans and the neuroprotective effects were attributed to its anti-oxidant activities, supported by the increase in superoxide dismutase, catalase and the diminution of acetylcholinesterase and reactive oxygen species levels. In addition, the Cullin-3 inhibitor significantly restored the behavioral deficits in the transgenic C. elegans. Conclusion: Taken together, these findings highlight the potential utility of Cullin-3 inhibition to block the persistent neuronal death in PD. Further studies focusing on Cullin-3 and its mechanism of action would be interesting.


2021 ◽  
Vol 9 ◽  
pp. 232470962110297
Author(s):  
Justin Cozza ◽  
Tuong Vi Cassandra Do ◽  
Shyam Ganti ◽  
Jayaramakrishna Depa

We report a rare case of a 32-year-old male who ingested 32.4 to 54 mg of colchicine and presented after 44 hours. He developed progressive multiple organ failure with shock, acute kidney failure, troponemia, pancytopenia, absolute neutropenia, disseminated intravascular coagulation, acute liver failure, rhabdomyolysis, and lactic acidosis. He also developed electrolyte abnormalities and refractory hypoglycemia. Initial treatment consisted of activated charcoal, fluids, and broad-spectrum antibiotics with supportive treatment of mechanical ventilation, hemodialysis, vasopressors, N-acetylcysteine, colony-stimulating factors, and blood products. Literature shows potential benefit of colchicine-specific Fab fragments for acute toxicity with limited studies and is not currently available in the United States. Further research for N-acetylcysteine protocol for acute liver failure in colchicine toxicity and potential use of colchicine-specific Fab fragments is needed. Our case demonstrates the importance of early use of activated charcoal for ingestion overdose with the incorporation of poison control into multidisciplinary team for coordinated patient care.


Uro ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 76-81
Author(s):  
Gopal Narang ◽  
Tim Shimon ◽  
Jonathan Moore ◽  
Megan Hager ◽  
Filippo Pinto e Vairo ◽  
...  

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare tubulopathy characterized by renal loss of calcium and magnesium leading to progressive renal failure. The disorder is caused by variants to the tight junction proteins claudin-16 and -19. While rare, this disorder causes a significant burden to patients based on its clinical manifestations of various electrolyte abnormalities, nephrocalcinosis, and early progression to renal failure. In this report we describe the diagnosis of a novel variant of CLDN16 which clinically presented with severe hypomagnesemia, hypocalcemia, nephrocalcinosis, and renal failure.


2020 ◽  
Vol 2020 (11) ◽  
Author(s):  
Pool Tobar ◽  
Alejandro Sanchez-Nadales ◽  
Elena Caldeira ◽  
Peguy Saad

ABSTRACT Blastomyces dermatitidis is an endemic mold infection commonly seen in the midwestern of the USA and rarely affects pregnant women. The most common presentation is a pulmonary infection with variable degrees of severity. Of note, the clinical and radiographic findings of pulmonary blastomycosis can be mistaken for other pulmonary pathologies, thus earning the title of ‘the great pretender’. The treatment of choice of infected pregnant patients is amphotericin B, which is known to produce electrolyte imbalances. However, it infrequently causes severe, prolonged and profound hypokalemia and hypomagnesemia. We present the case of a 27-year-old pregnant patient with pulmonary blastomycosis presenting with a lung mass suspicious of malignancy and treated with amphotericin B with subsequent prolonged refractory hypokalemia and hypomagnesemia. Keywords pulmonary blastomycosis pregnancy biopsy computed tomography angiography liposomal amphotericin B


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