A Case of Mannitol Hypersensitivity

Lightner, Donita; Braganca, Kevin C. De; Gilheeney, Stephen W.; Khakoo, Yasmin; Krämer, Kim; Balas, Morad

doi:10.1097/mph.0b013e31828d5b3e

Cited by 12 publications

(10 citation statements)

References 6 publications

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“…In addition, a study in spontaneously hypertensive rats indicated mannitol activates cardiac and renal cell death implicating heart and renal damage (72). Furthermore, clinical studies have strongly emphasized the adverse effects of mannitol in diabetic patients including nephrotoxicity (39) and acute renal failure (12,59,66), as well as anaphylactic reactions under certain pathological conditions (37).…”

Section: Discussionmentioning

confidence: 99%

Hydrogen sulfide inhibits Ca²⁺-induced mitochondrial permeability transition pore opening in type-1 diabetes

John

Kundu

Pushpakumar

et al. 2019

American Journal of Physiology-Endocrinology and Metabolism

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Hydrogen sulfide (H2S) attenuates N-methyl-d-aspartate receptor-R1 (NMDA-R1) and mitigates diabetic renal damage; however, the molecular mechanism is not well known. Whereas NMDA-R1 facilitates Ca2+permeability, H2S is known to inhibit L-type Ca2+channel. High Ca2+activates cyclophilin D (CypD), a gatekeeper protein of mitochondrial permeability transition pore (MPTP), thus facilitating molecular exchange between matrix and cytoplasm causing oxidative outburst and cell death. We tested the hypothesis of whether NMDA-R1 mediates Ca2+influx causing CypD activation and MPTP opening leading to oxidative stress and renal injury in diabetes. We also tested whether H2S treatment blocks Ca2+channel and thus inhibits CypD and MPTP opening to prevent renal damage. C57BL/6J and Akita (C57BL/6J-Ins2Akita) mice were treated without or with H2S donor GYY4137 (0.25 mg·kg−1·day−1ip) for 8 wk. In vitro studies were performed using mouse glomerular endothelial cells. Results indicated that low levels of H2S and increased expression of NMDA-R1 in diabetes induced Ca2+permeability, which was ameliorated by H2S treatment. We observed cytosolic Ca2+influx in hyperglycemic (HG) condition along with mitochondrial-CypD activation, increased MPTP opening, and oxidative outburst, which were mitigated with H2S treatment. Renal injury biomarker KIM-1 was upregulated in HG conditions and normalized following H2S treatment. Inhibition of NMDA-R1 by pharmacological blocker MK-801 revealed similar results. We conclude that NMDA-R1-mediated Ca2+influx in diabetes induces MPTP opening via CypD activation leading to increased oxidative stress and renal injury, and H2S protects diabetic kidney from injury by blocking mitochondrial Ca2+permeability through NMDA-R1 pathway.

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Section: Discussionmentioning

confidence: 99%

Hydrogen sulfide inhibits Ca²⁺-induced mitochondrial permeability transition pore opening in type-1 diabetes

John

Kundu

Pushpakumar

et al. 2019

American Journal of Physiology-Endocrinology and Metabolism

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“…After the infusion was stopped, there was an immediate clinical improvement. The patient was given hydrocortisone, hydroxyzine, and ranitidine without further incident [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

“…Studies done in the 1960s suggest that hyperosmolar stimulation can lead to mannitol sensitivity in patients as opposed to an allergic response [ 10 ]. If leukocytes are placed under the right in vitro conditions, basophils can release histamine independent of IgE [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

Mannitol Anaphylaxis in the Setting of Septic Emboli-Induced Intracranial Hemorrhage

Parker¹,

Priyadarshi²

2022

Cureus

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Neurological complications are a significant problem in bacterial endocarditis. Cerebral embolism is the most frequent concern. Acute embolic disease may trigger focal seizures or mycotic aneurysms. Miliary infection is also common, and lumbar puncture can guide in determining the infective organism. Purulent cerebrospinal fluid (CSF) consists often of Staphylococcus aureus, a virulent organism, whereas non-virulent organisms (i.e., viridans streptococci) have normal CSF formulae. Microscopic abscesses suggest the potential for aneurysm from bacterial endocarditis amplifying the risk of intracranial hemorrhage. Mannitol and hypertonic (3%) saline are intravenous medications used as a rescue treatment for brain hemorrhage. A patient diagnosed with mycoplasma pneumonia and septic shock secondary to tricuspid endocarditis with extensive pulmonary emboli and metastatic infection to his spine was initiated on antibiotics. He developed a massive intracranial bleed from the rupture of mycotic septic emboli and was given mannitol to decrease intracranial pressure, which caused anaphylaxis.

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“…Structurally, it is a low molecular-weight, inert hapten. Current guidelines for interpretation of drug allergy testing 10 indicate that positive intradermal and skin-prick tests to mannitol would favour an IgE-mediated mechanism underlying clinical anaphylaxis in both cases. The potential sources of immune sensitisation to mannitol are intriguing; previous mannitol exposure in medications, or other products like mouthwash, chewing gums and processed foods, are possibilities.…”

Section: Discussionmentioning

confidence: 99%

“…Both patients had a history of intolerance to mushrooms and avoidance of mannitol in parenteral solutions may have prevented the intraoperative anaphylaxis. There are published reports documenting hypersensitivity reactions to mannitol infusion 10,12,13 . After a thorough literature search, we found only one case reporting anaphylaxis to mannitol where it was used as an excipient in a cisapride tablet 11 .…”

Section: Discussionmentioning

confidence: 99%

Anaphylaxis following Intravenous Paracetamol: The Problem is the Solution

Jain

Green

Rose

2015

Anaesth Intensive Care

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Paracetamol is a ubiquitous analgesic and antipyretic that is widely administered, including by anaesthetists. Immediate hypersensitivity reactions to intravenous paracetamol are particularly rare. We report two cases involving four separate episodes of anaphylaxis to intravenous paracetamol in different perioperative settings without a past history of intolerance to the oral form. The allergological investigations are described, during which it became evident that both patients were allergic to an excipient (mannitol) present in the formulation and that neither was allergic to the principal agent (paracetamol). The importance of referral and investigation of perioperative drug reactions is underscored by these two cases.

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A Case of Mannitol Hypersensitivity

Abstract: Mannitol is used for increased intracranial pressure and prevention of nephrotoxicity. We present a case report of a patient who experienced an anaphylactic response to mannitol and review the literature.

Cited by 12 publications

References 6 publications

Hydrogen sulfide inhibits Ca²⁺-induced mitochondrial permeability transition pore opening in type-1 diabetes

Hydrogen sulfide inhibits Ca²⁺-induced mitochondrial permeability transition pore opening in type-1 diabetes

Mannitol Anaphylaxis in the Setting of Septic Emboli-Induced Intracranial Hemorrhage

Anaphylaxis following Intravenous Paracetamol: The Problem is the Solution

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A Case of Mannitol Hypersensitivity

Abstract: Mannitol is used for increased intracranial pressure and prevention of nephrotoxicity. We present a case report of a patient who experienced an anaphylactic response to mannitol and review the literature.

Cited by 12 publications

References 6 publications

Hydrogen sulfide inhibits Ca2+-induced mitochondrial permeability transition pore opening in type-1 diabetes

Hydrogen sulfide inhibits Ca2+-induced mitochondrial permeability transition pore opening in type-1 diabetes

Mannitol Anaphylaxis in the Setting of Septic Emboli-Induced Intracranial Hemorrhage

Anaphylaxis following Intravenous Paracetamol: The Problem is the Solution

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Product

Resources

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Hydrogen sulfide inhibits Ca²⁺-induced mitochondrial permeability transition pore opening in type-1 diabetes

Hydrogen sulfide inhibits Ca²⁺-induced mitochondrial permeability transition pore opening in type-1 diabetes