Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Poor target cell specificity is currently a major shortcoming of nanoparticles (NPs) used for biomedical applications. It causes significant material loss to off-target sites and poor availability at the intended delivery site. To overcome this limitation, we designed particles that identify cells in a virus-like manner. As a blueprint, we chose a mechanism typical of influenza A virus particles in which ectoenzymatic hemagglutinin activation by target cells is a mandatory prerequisite for binding to a secondary target structure that finally confirms cell identity and allows for uptake of the virus. We developed NPs that probe mesangial cells for the presence of angiotensin-converting enzyme on their surface using angiotensin I (Ang-I) as a proligand. This initial interaction enzymatically transforms Ang-I to a secondary ligand angiotensin II (Ang-II) that has the potential to bind in a second stage to Ang-II type-1 receptor (AT1R). The presence of the receptor confirms the target cell identity and triggers NP uptake via endocytosis. Our virus-mimetic NPs showed outstanding target-cell affinity with picomolar avidities and were able to selectively identify these cells in the presence of 90% off-target cells that carried only the AT1R. Our results demonstrate that the design of virus-mimetic cell interactive NPs is a valuable strategy to enhance NP specificity for therapeutic and diagnostic applications. Our set of primary and secondary targets is particularly suited for the identification of mesangial cells that play a pivotal role in diabetic nephropathy, one of the leading causes of renal failure, for which currently no treatment exists.
 ...
PMID:Influenza A virus mimetic nanoparticles trigger selective cell uptake. 3103 31

Lisinopril is an angiotensin converting enzyme inhibitor (ACE-I) that has been on market for more than 25 years. ACE-I are usually well tolerated and rarely have serious or life-threatening side effects. We describe an unusual presentation of fulminant hepatic cholestasis probably secondary to lisinopril. To our knowledge, this is the second case report which shows lisinopril-induced liver injury though a cholestatic mechanism. The patient was a 59-year-old woman with type 2 diabetes, a high body mass index and hypertension, who presented with a 5-week history of jaundice and itching. She had been started on lisinopril for diabetic nephropathy 8 weeks before admission. Other causes for cholestasis had been excluded through non-invasive immunology and virology screening, an ultrasound of the liver, magnetic resonance cholangiopancreatography and a liver biopsy. The biopsy was consistent with drug-induced liver injury. Lisinopril was stopped 2 weeks before admission. The patient's hospital stay was complicated by contrast nephropathy and influenza A which were both treated appropriately. Unfortunately, the liver cholestasis did not completely resolve following withdrawal of lisinopril and the patient died after 4 months. A literature search yielded only six other reported cases of lisinopril-induced liver injury. Five cases described hepatocellular damage and one showed cholestatic injury.
 ...
PMID:Lisinopril-Induced Liver Injury: An Unusual Presentation and Literature Review. 3266 26