Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neisseria gonorrhoeae is the bacterium that causes gonorrhea, a major sexually transmitted disease and a significant cofactor for human immunodeficiency virus transmission. The retactile N. gonorrhoeae type IV pilus (Tfp) mediates twitching motility and attachment. Using live-cell microscopy, we reveal for the first time the dynamics of twitching motility by N. gonorrhoeae in its natural environment, human epithelial cells. Bacteria aggregate into microcolonies on the cell surface and induce a massive remodeling of the microvillus architecture. Surprisingly, the microcolonies are motile, and they fuse to form progressively larger structures that undergo rapid reorganization, suggesting that bacteria communicate with each other during infection. As reported, actin plaques form beneath microcolonies. Here, we show that cortical plaques comigrate with motile microcolonies. These activities are dependent on pilT, the Tfp retraction locus. Cultures infected with a pilT mutant have significantly higher numbers of apoptotic cells than cultures infected with the wild-type strain. Inducing pilT expression with isopropyl-beta-D-thiogalactopyranoside partially rescues cells from infection-induced apoptosis, demonstrating that Tfp retraction is intrinsically cytoprotective for the host. Tfp-mediated attachment is therefore a continuum of microcolony motility and force stimulation of host cell signaling, leading to a cytoprotective effect.
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PMID:Dynamics of Neisseria gonorrhoeae attachment: microcolony development, cortical plaque formation, and cytoprotection. 1768 45

Drug-induced QT prolongation is a potentially dangerous adverse effect of some medication combinations. When QT prolongation progresses to torsade de pointes, life-threatening or fatal outcomes may result. A 57-year-old man with a history of human immunodeficiency syndrome on abacavir, nevirapine, tenofovir, voriconazole, and methadone presented to the emergency department with a chief complaint of new-onset seizures. The physical exam was unremarkable. The electrocardiogram demonstrated sinus bradycardia and a prolonged QT(c) interval of 690 ms. In the emergency department, he had several episodes of torsade de pointes (TdP) and ventricular tachycardia that resolved spontaneously. These episodes were accompanied by an alteration in mentation and generalized twitching. Magnesium and amiodarone were effective in terminating the dysrhythmia. The patient had multiple risk factors for prolonged QT syndrome including human immunodeficiency virus infection, methadone therapy, and polypharmacy leading to potential drug interactions. Physicians must be aware of multidrug interactions potentiating QT prolongation and leading to torsade de pointes.
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PMID:Torsade de pointes caused by polypharmacy and substance abuse in a patient with human immunodeficiency virus. 1938 21

We report the case of a 50-year-old human immunodeficiency virus-positive patient with stage IV KRAS-mutated colorectal cancer who experienced visible muscle twitching in the right lateral triceps brachii from irinotecan administration for which typical supportive care measures were unsuccessful, including the administration of atropine and slowing down the infusion rate. The patient was able to tolerate this reaction and received 20 cycles of irinotecan-based chemotherapy despite experiencing the muscle twitching with every cycle at the same onset, duration, and severity. It is possible that competitive metabolism by concomitant medications metabolized by CYP3A4 or UGT1A1 was responsible for this event. Due to ethical concerns, we were unable to formally assess the drug interaction by discontinuing the suspected interacting medications and re-initiating them to evaluate the effects. A formal pharmacokinetic study may be warranted to better elucidate these potential drug interactions.
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PMID:Irinotecan-induced muscle twitching from a possible drug interaction: A case report. 2874 2