Introduction: Turmeric, a plant prevalent in South Asia, is often marketed to be safe, with many benefits including antioxidant and anti-inflammatory effects. Hepatotoxicity, a rare adverse effect, has only been documented in a few case reports. Here we present a case of turmeric Drug Induced Liver Injury (DILI) with normalization of liver function tests after its cessation. Case Description/Methods: A 62-year-old female with a history of hypertension presented with nausea and generalized abdominal pain for five days. She denied taking medications other than hydrochlorothiazide. Further interview noted that she initiated turmeric tea over the preceding three weeks. On physical exam, she had scleral icterus and right upper quadrant tenderness. Laboratory workup showed AST 1510 U/L, ALT 1889 U/L, total bilirubin 13.9 mg/dL, direct bilirubin 8.1 mg/dL, ALP 134 U/L, LDH 542 U/L, with an ALT/LDH ratio of 3.49. INR was normal. Ultrasound revealed findings consistent with acute hepatitis. Ferritin, ceruloplasmin, and acetaminophen levels were normal. Alpha-1-antitrypsin, anti-mitochondrial, and anti-smooth muscle antibodies were unremarkable. Viral serologies were normal. The patient improved with turmeric cessation, with complete resolution of abnormal liver enzymes on follow-up. Discussion: Turmeric, previously considered safe, has now been reported to be associated with DILI in a few case reports. Our case adds to the growing body of evidence supporting turmeric induced DILI. Although we could not uncover the exact dose, we do establish a high probability of adverse effects from turmeric using the validated Roussel Uclaf Causality Method (RUCAM) scoring system. Our patient scored 9, with a score .8 representing a high probability. Turmeric induced DILI is thought to be both dose dependent and associated with formulations that contain supplements or nanoparticles that increase turmeric's bioavailability. Lombardi et al. and Sohal et al. for example both report several cases of acute hepatitis associated with turmeric preparations developed with piperine (black pepper), which has been shown to increase the absorption of turmeric by 2000%. In our case, the patient's turmeric tea also included black pepper, which likely explains the hepatotoxicity. This case underscores the importance of supplement history, with an emphasis on turmeric, when evaluating for potential causes of DILI.
Cystic fibrosis (CF) is a life‐threatening genetic disease caused by mutations in the CF transmembrane conductance regulator gene. It is the most common genetic disease among Caucasians. There is an urgent need to create more therapies for CF since current drugs are not effective in treating all the mutations that cause this disease. Furthermore, gene therapy is a potential treatment for CF airway disease. Because of this, various viral‐based gene transfer vectors have been evaluated for their efficiency in correcting the CF airway disease phenotype. This project aimed to compare side‐by‐side the differences in the transduction efficiency and targeting of specific cell types of adenovirus (Ad)‐based and adeno‐associated virus (AAV)‐based vectors in different models of the airway. Different serotypes of AAV, namely 1, 2, 5, 6, and Ad5‐based vectors, expressing green fluorescent protein (GFP), firefly luciferase (ffLuc) or ß‐galactosidase (LacZ) were assessed in in vitro and in vivo gene transfer studies. Madin‐Darby Canine Kidney (MDCK) cells were grown submerged on plastic, and human airway epithelial (HAE) cells were grown on transwells and fed only from the basolateral side to attempt to model the human conducting airways. The viral vectors expressing GFP were tested at doses of 102–103 genome copies (GC) for AAV or plaque‐forming unit (pfu) for Ad, and the level of transduction was assessed at different time points. The data demonstrates that in MDCK and HAE cells, the highest transduction was achieved by the Ad5 vector followed by the AAV2 vector, while AAV6 had the lowest transduction. Additionally, as examined in HAE cells, the age of the culture impacts transduction efficiency. In parallel, AAV vectors 1, 2, 5, 6 (at a dose of 8×1010 – 3×1011 GC) and Ad5 vector (at a dose of 1×1011 pfu) expressing ffLuc or LacZ were intranasally delivered to mice to assess the transduction efficiency in the epithelium of both the nose and lungs. AAV6 was the most efficient at transducing the cells of the nasal epithelium of mice and AAV5, at transducing lung cells. AAV2 did not transduce airway cells in mice. In conclusion, we confirmed that the viral vectors have different transduction profiles in different models of airway epithelium. More airway models should be studied to better understand which are more useful for preclinical assessments of CF gene therapeutics. Support or Funding Information This project was supported by the National Heart, Lung, and Blood Institute (R25‐HL084665‐14).
To evaluate gene therapy for retinal disorders, appropriate models of the human eye are needed. Nonhuman primate eyes offer significant advantages over rodent eyes. However, current preparation methods have limitations. Here, a protocol is described for histological processing of nonhuman primate eyes after gene transfer. The user dissects unfixed eyes, flattens the globe parts within filter paper, and performs formalin fixation and paraffin embedding. This method obviates the need for harsh fixatives, allowing subsequent immunostaining or in situ hybridization while preserving tissue integrity for histopathological evaluation. Moreover, the straight orientation of the retinal cell layers is ideal for image analysis.
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