- Repetitive bilirubin measurements in preterm infants prior to phototherapy: is it wise to use the rate of rise? [Journal Article]
- PRPediatr Res 2019 Jun 18
- Coupling AAV-mediated promoterless gene targeting to SaCas9 nuclease to efficiently correct liver metabolic diseases. [Journal Article]
- JIJCI Insight 2019 Jun 18; 5
- Non-integrative AAV-mediated gene therapy in the liver is effective in adult patients, but faces limitations in pediatric settings due to episomal DNA loss during hepatocyte proliferation. Gene targe…
Non-integrative AAV-mediated gene therapy in the liver is effective in adult patients, but faces limitations in pediatric settings due to episomal DNA loss during hepatocyte proliferation. Gene targeting is a promising approach by permanently modifying the genome. We previously rescued neonatal lethality in Crigler-Najjar mice by inserting a promoterless human uridine glucuronosyl transferase A1 (UGT1A1) cDNA in exon 14 of the albumin gene, without the use of nucleases. To increase recombination rate and therapeutic efficacy, here we used CRISPR/SaCas9. Neonatal mice were transduced with two AAVs: one expressing the SaCas9 and sgRNA, and one containing a promoterless cDNA flanked by albumin homology regions. Targeting efficiency increased ~26-fold with an eGFP reporter cDNA, reaching up to 24% of eGFP-positive hepatocytes. Next, we fully corrected the diseased phenotype of Crigler-Najjar mice by targeting the hUGT1A1 cDNA. Treated mice had normal plasma bilirubin up to 10 months after administration, hUGT1A1 protein levels were ~6-fold higher than in WT liver, with a 90-fold increase in recombination rate. Liver histology, inflammatory markers, and plasma albumin were normal in treated mice, with no off-targets in predicted sites. Thus, the improved efficacy and reassuring safety profile support the potential application of the proposed approach to other liver diseases.
- Successful treatment of Yersinia pseudotuberculosis hepatitis in a cat presenting with neurological abnormalities. [Case Reports]
- JOJFMS Open Rep 2019 Jan-Jun; 5(1):2055116919853644
- A 3-year-7-month-old female neutered domestic shorthair cat was presented for further investigation of acute-onset neurological abnormalities, including marked decreased mentation, ataxia and abnorma…
A 3-year-7-month-old female neutered domestic shorthair cat was presented for further investigation of acute-onset neurological abnormalities, including marked decreased mentation, ataxia and abnormal cranial nerve responses, with concurrent marked pyrexia (40ºC). Initial blood testing was non-specific with mild-to-moderate increases in alanine aminotransferase (ALT) (194 IU/l; reference interval [RI] 17-62 IU/l), aspartate aminotransferase (AST; 150 IU/l [RI 0-51 IU/l]) and total bilirubin (20 µmol/l; RI 0-11 µmol/l), and neutropenia (1.17 ×109/l; RI 2.5-12.5 ×109/l). Brain MRI and cerebrospinal fluid analysis were unremarkable and Toxoplasma serology was negative. Worsening of hepatic biochemical parameters (ALT 265 IU/l, AST 205 IU/l, total bilirubin 42.9 µmol/l) led to further investigations for liver disease, including ultrasound, fine-needle aspirate cytology, histology, fluorescent in situ hybridisation and culture of liver tissue and bile, resulting in a diagnosis of Yersinia pseudotuberculosis hepatitis. The cat was treated with a combination of potentiated amoxicillin (62.5 mg PO q12h), marbofloxacin (5mg PO q24h) and combined s-adenosyl methionine (SAMe)/silybin (90 mg PO q24h), and made a full recovery. Follow-up over 14 months identified a persistent mild increase in ALT, despite no apparent ongoing disease.
- Autologous Bone Marrow Stem Cell Transplantation in Liver Cirrhosis after Correcting Nutritional Anomalies, A Controlled Clinical Study. [Journal Article]
- CJCell J 2019; 21(3):268-273
- CONCLUSIONS: We have successfully improved the conditions of preparing -BM-derived stem cells for transplantation. Although these cells are relatively safe and have been shown to improve some clinical signs and symptoms temporarily, there need to be more basic studies regarding the preparation steps for effective clinical use (Registration number: IRCT2014091919217N1).
- [The experiment study of endovascular denervation in treatment of cancer pain]. [Journal Article]
- ZYZhonghua Yi Xue Za Zhi 2019 Jun 18; 99(23):1814-1818
- CONCLUSIONS: EDN could be applied in beagles safely and feasibly.
- Protection against nonalcoholic steatohepatitis through targeting IL-18 and IL-1alpha by luteolin. [Journal Article]
- PRPharmacol Rep 2019 Mar 15; 71(4):688-694
- CONCLUSIONS: Luteolin can protect against non-alcoholic steatohepatitis through targeting the pro-inflammatory IL-1 and Il-18 pathways in addition to an antioxidant effect.
- Association of lower serum bilirubin with loss of residual kidney function in peritoneal dialysis patients. [Journal Article]
- TATher Apher Dial 2019 Jun 17
- CONCLUSIONS: This study suggests that low serum total bilirubin levels are associated with loss of RKF in PD patients. This article is protected by copyright. All rights reserved.
- Autologous stem cell transplantation for patients with viral hepatitis-induced liver cirrhosis: a systematic review and meta-analysis. [Journal Article]
- EJEur J Gastroenterol Hepatol 2019 Jun 14
- CONCLUSIONS: Autologous stem cell transplantation might have beneficial effects on patients with viral hepatitis-induced LC and is relatively safe for these patients. Further high-quality randomized controlled trials are needed.
- [Alcoholic hepatitis]. [Classical Article]
- RMRev Med Liege 2019; 74(5-6):326-331
- Alcoholic hepatitis is a syndrome defined primarily by the clinical onset of jaundice in patients with a concomitant heavy consumption of alcoholic beverages. This pathology is managed by alcohol wit…
Alcoholic hepatitis is a syndrome defined primarily by the clinical onset of jaundice in patients with a concomitant heavy consumption of alcoholic beverages. This pathology is managed by alcohol withdrawal with a 30-day survival rate of 90 %. For patients with severe alcoholic hepatitis, with a Maddrey score greater than 32 (taking into account bilirubin and prothrombin time), treatment with corticosteroids is discussed provided that a possible infection can be sufficiently excluded or adequately managed. The administration of corticosteroids is continued for 28 days if the Lille score, calculated after 7 days of treatment, is favourable (inferior to 0.45), leading to a survival rate of 80-90 %. However, if the Lille score is unfavourable (superior to 0.45), the prognosis is bad, with a survival of only 25-30 % at 6 months. Special attention needs to be paid to assure a sufficient caloric intake during the treatment period for a successful management. Liver transplantation, previously prohibited for this indication, can be discussed under certain circumstances. However, the success of treatment is contingent upon the alcohol withdrawal. Innovative drugs are currently under investigation to improve the prognosis of this condition.
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- Total syntheses of the bilirubin oxidation end product Z-BOX C and its isomeric form Z-BOX D. [Journal Article]
- OBOrg Biomol Chem 2019 Jun 17
- Oxidative degradation products of bilirubin (BOXes) are biologically highly active and certain BOXes cause long-lasting narrowing of cerebral blood vessels presumably with a significant role in subar…
Oxidative degradation products of bilirubin (BOXes) are biologically highly active and certain BOXes cause long-lasting narrowing of cerebral blood vessels presumably with a significant role in subarachnoid hemorrhage. Due to the fact that mode of action as well as fate of these BOXes is widely unknown, larger amounts of these bilirubin degradation end products are required. The total synthesis of colorless (Z)-3-(5-(2-amino-2-oxoethylidene)-4-methyl-2-oxo-2,5-dihydro-1H-pyrrol-3-yl)propanoic acid (BOX C) succeeds via a seven-step procedure with a total yield of 20%. Its isomeric form (Z)-3-(2-(2-amino-2-oxoethylidene)-4-methyl-5-oxo-2,5-dihydro-1H-pyrrol-3-yl)propanoic acid (BOX D) can be prepared via a five-step protocol with a yield of 30%. NMR and crystallographic studies reveal that charge delocalization within the conjugated π-systems of BOXes C and D is negligible. Exposure of solutions of Z-BOX C and Z-BOX D to bright sunlight leads to Z/E-isomerization and mixtures of the respective E/Z-BOXes C and D.