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Frontiers in Pediatrics 2023Alport syndrome (AS) and Wilson's disease (WD) are genetic diseases that could lead to kidney damage. Herein, we report the clinical features and gene variants in a...
BACKGROUND
Alport syndrome (AS) and Wilson's disease (WD) are genetic diseases that could lead to kidney damage. Herein, we report the clinical features and gene variants in a patient with WD and X-linked AS.
CASE PRESENTATION
The proband was a 12-year-old boy diagnosed with AS coexisting with WD at the age of 11 years. The patient underwent a medical check-up when he was 4 years and 8 months. Laboratory tests revealed elevated liver enzymes, decreased serum ceruloplasmin, increased 24-h urinary copper excretion, and one variant in the gene. Then, the patient was diagnosed with WD. After 2 months of treatment with D-penicillamine and zinc salt, his liver function had recovered to normal levels, but he presented with microscopic hematuria. The hematuria did not resolve after switching to dimercaptosuccinic acid from D-penicillamine. In addition, he presented with proteinuria 3 years later. A renal biopsy was performed more than 6 years after the patient was diagnosed with WD, and electron microscopy showed that the basement membrane thickness was uneven, layered, and focal torn. Copper staining was negative. A genetic analysis identified a hemizygous variant (c.1718G > A, p. Gly573Asp) in and a homozygous variant (c.2975C > T, p. Pro992leu) in . The patient's urine protein-creatinine ratio was less than 1.0 mg/mg after a 1 year of follow-up, after enalapril was administered for treating AS.
CONCLUSION
This case highlights a lack of improvement in renal function after conventional treatment provides a possible indication for performing renal biopsy or genetic testing to determine the etiology in order to facilitate subsequent clinical management. Clinicians should prevent the occurrence of diagnostic inaccuracies caused by diagnostic anchoring because an accurate diagnosis is essential for achieving precise treatment and improved prognosis.
PubMed: 37063668
DOI: 10.3389/fped.2023.1107280 -
Journal of Pharmaceutical and... May 2023To investigate the metabolic mechanisms of Chinese and Western medicines on the metabolic network of striatal injury in a copper-loaded rat model of Wilson disease (WD)...
OBJECTIVE
To investigate the metabolic mechanisms of Chinese and Western medicines on the metabolic network of striatal injury in a copper-loaded rat model of Wilson disease (WD) from a metabolomic perspective.
METHODS
We divided 60 rats into 4 groups of 15 rats each according to a random number table, namely the control group, the model group, the Bushen Huoxue Huazhuo Recipe group, and the penicillamine group, and subsequently replicated the WD copper-loaded rat model according to the literature method for a total of 12 weeks. From the 7th week onwards, each intervention group was given an equivalent dose of the corresponding drug, and the control and model groups were given an equal volume of saline gavage until the end of the model replication. We used H NMR metabolomics techniques combined with multivariate statistical methods to describe the changes in the striatal metabolic profile of nerve injury in Wilson's disease and to analyze the effect of different treatments on their biomarker interventions.
RESULTS
Nerve cell damage was evident in the WD copper-loaded rat model and could be reduced to varying degrees by different methods of intervention in the striatal nerve cells. The content of glycine, serine metabolism, and valine metabolism decreased in WD copper-loaded rat model; aspartate content increased after penicillamine intervention; glycolytic metabolism, valine metabolism, taurine metabolism, and tyrosine metabolism increased in the group of Bushen Huoxue Huazhuo Recipe.
CONCLUSION
Different intervention methods of Chinese and Western medicine affect aspartate, glycolysis, taurine, tyrosine, valine, and carbon metabolism in striatal tissues of WD copper-loaded rats, and can regulate the metabolism of small molecules, which in turn have certain repairing effects on nerve damage in WD copper-loaded rats.
Topics: Rats; Animals; Hepatolenticular Degeneration; Copper; Proton Magnetic Resonance Spectroscopy; Aspartic Acid; Penicillamine; Metabolomics
PubMed: 37018958
DOI: 10.1016/j.jpba.2023.115355 -
Food Chemistry Aug 2023Seafood is highly perishable and monitoring its freshness this thus an important issue. For the first time, the current study developed a dual-mode freshness indicator...
Seafood is highly perishable and monitoring its freshness this thus an important issue. For the first time, the current study developed a dual-mode freshness indicator based on d-penicillamine capped bimetallic gold/copper nanoclusters (DPA-Au/CuNCs) as a response probe for simultaneous monitoring of ammonia and temperatures to assess seafood freshness. Results indicated that the prepared DPA-Au/CuNCs have good sensitivity toward ammonia, with a limit of detection of 0.14 ppm. The indicator as a gas sensor for ammonia vapour detection exhibited highly recognizable fluorescence colour changes and the variations from white to yellow were observed with increasing storage temperature under natural light. For confirming its practical applications, the indicator was used to simultaneously monitor ammonia and temperatures during the storage of shrimp and fish, showing good potential for practical applications in evaluating seafood freshness for the food industry.
Topics: Animals; Ammonia; Fishes; Product Packaging; Seafood; Temperature; Copper; Gold; Nanostructures
PubMed: 37001353
DOI: 10.1016/j.foodchem.2023.135929 -
Global Pediatric Health 2023Wilson disease is a rare autosomal recessive genetic disease, caused by the mutation of the ATP7B gene leading to decreased secretion of serum ceruloplasmin in blood and...
Wilson disease is a rare autosomal recessive genetic disease, caused by the mutation of the ATP7B gene leading to decreased secretion of serum ceruloplasmin in blood and decrease biliary excretion of copper leading to toxic level accumulation in the liver, brain, kidney, and cornea, resulting in development of characteristic liver disease and neuropsychiatric symptoms. Our case presented with mainly clumsiness and gait abnormality without any psychiatric component and any history of liver disease. A 13-year old male, born out of non-consanguineous marriage, presented with clumsy walking and slurring of speech. The child also complained of poor handwriting and slipping of slipper from foot, without any history of abnormal behavior and poor scholastic performance. On examination gait was abnormal with sidewise swaying, increased muscle tone with rigidity and bilateral flexor plantar reflex. Slit lamp examination of eyes revealed bilateral Kayser-Fleischer rings. Serum ceruloplasmin was low (0.03 g/L) and 24-hour urinary copper was high (119.64 μg/day). MRI brain showed B/L putamen hyperintensity and panda sign suggestive of Wilson disease. After the diagnosis of Wilson disease was made, patient was treated with penicillamine and zinc. Child was also followed-up and re-examination showed slight improvement. Though not rare, Wilson disease is an uncommon entity with varied presentations and disabling consequences. Hence high index of suspicion and clinical correlation is required to diagnose it. Early initiation of treatment and good compliance ensure a better outcome.
PubMed: 36992844
DOI: 10.1177/2333794X231163418 -
Frontiers in Immunology 2023The pro-inflammatory cytokine interleukin-1β (IL-1β) plays a central role in host defense against infections. High systemic IL-1β levels, however, promote the...
OBJECTIVE
The pro-inflammatory cytokine interleukin-1β (IL-1β) plays a central role in host defense against infections. High systemic IL-1β levels, however, promote the pathogenesis of inflammatory disorders. Therefore, mechanisms controlling IL-1β release are of substantial clinical interest. Recently, we identified a cholinergic mechanism inhibiting the ATP-mediated IL-1β release by human monocytes nicotinic acetylcholine receptor (nAChR) subunits α7, α9 and/or α10. We also discovered novel nAChR agonists that trigger this inhibitory function in monocytic cells without eliciting ionotropic functions at conventional nAChRs. Here, we investigate the ion flux-independent signaling pathway that links nAChR activation to the inhibition of the ATP-sensitive P2X7 receptor (P2X7R).
METHODS
Different human and murine mononuclear phagocytes were primed with lipopolysaccharide and stimulated with the P2X7R agonist BzATP in the presence or absence of nAChR agonists, endothelial NO synthase (eNOS) inhibitors, and NO donors. IL-1β was measured in cell culture supernatants. Patch-clamp and intracellular Ca imaging experiments were performed on HEK cells overexpressing human P2X7R or P2X7R with point mutations at cysteine residues in the cytoplasmic C-terminal domain.
RESULTS
The inhibitory effect of nAChR agonists on the BzATP-induced IL-1β release was reversed in the presence of eNOS inhibitors (L-NIO, L-NAME) as well as in U937 cells after silencing of eNOS expression. In peripheral blood mononuclear leukocytes from eNOS gene-deficient mice, the inhibitory effect of nAChR agonists was absent, suggesting that nAChRs signal eNOS to inhibit the BzATP-induced IL-1β release. Moreover, NO donors (SNAP, S-nitroso-N-acetyl-DL-penicillamine; SIN-1) inhibited the BzATP-induced IL-1β release by mononuclear phagocytes. The BzATP-induced ionotropic activity of the P2X7R was abolished in the presence of SIN-1 in both, oocytes and HEK cells over-expressing the human P2X7R. This inhibitory effect of SIN-1 was absent in HEK cells expressing P2X7R, in which C377 was mutated to alanine, indicating the importance of C377 for the regulation of the P2X7R function by protein modification.
CONCLUSION
We provide first evidence that ion flux-independent, metabotropic signaling of monocytic nAChRs involves eNOS activation and P2X7R modification, resulting in an inhibition of ATP signaling and ATP-mediated IL-1β release. This signaling pathway might be an interesting target for the treatment of inflammatory disorders.
Topics: Humans; Mice; Animals; Interleukin-1beta; Leukocytes, Mononuclear; Receptors, Purinergic P2X7; Monocytes; Adenosine Triphosphate; Nitric Oxide Synthase
PubMed: 36969210
DOI: 10.3389/fimmu.2023.1140592 -
Euroasian Journal of... 2022Wilson's disease (WD) is a rare autosomal recessive disease, that can involve any organ of the body, the main ones being the liver and the brain. These patients can have...
AIM
Wilson's disease (WD) is a rare autosomal recessive disease, that can involve any organ of the body, the main ones being the liver and the brain. These patients can have varied presentations, ranging from having no symptoms to having neurological manifestations to features of chronic liver disease (CLD). Those patients that end up having CLD are prognosticated the Child-Turcotte-Pugh (CTP) score and the Model for End-stage Liver Disease (MELD) score. However, two specific scores exist for prognostication in patients having WD, namely, the Nazar score and the Dhawan score. However, these are yet to be validated nor has their use been implemented in clinical practice.
MATERIALS AND METHODS
Our study involved 65 patients with WD, comprising both the pediatric and the adult population. We aimed at evaluating the clinical manifestations the lab parameters and the management of these patients. Furthermore, we tried validating the Nazar and the Dhawan score and later compared them with the CTP and the MELD score, which are well-known prognostic tools in CLD.
RESULTS
Our patients were subdivided into the pediatric (more than 50%) and the adult group. The most common presenting complaint noted in both groups was abdominal distension. Values of the urine copper and serum ceruloplasmin did not defer between the pediatric and adult patients. Hepatic involvement is frequently seen in the pediatric age-group. Also, CTP class C was chiefly seen in pediatrics 17/33 (51.5%), while CTP class B was in adults 13/32 (40.6%). The mean Nazar score was 3 ± 3, while the mean Dhawan score was 5 ± 4. The main treatment offered for both groups was zinc along with penicillamine.
CONCLUSION
Our study showed the Dhawan score was comparable to the CTP and the MELD score in terms of predicting the disease severity of WD in our patient population.
HOW TO CITE THIS ARTICLE
Majid Z, Abrar G, Laeeq SM, . Clinical Characteristics and Comparison of Different Prognostic Scores in Wilson's Disease. Euroasian J Hepato-Gastroenterol 2022;12(2):69-72.
PubMed: 36959988
DOI: 10.5005/jp-journals-10018-1379 -
Scientific Reports Mar 2023Small diameter vascular grafts (SDVGs) are associated with a high failure rate due to poor endothelialization. The incorporation of a nitric oxide (NO) releasing system...
Small diameter vascular grafts (SDVGs) are associated with a high failure rate due to poor endothelialization. The incorporation of a nitric oxide (NO) releasing system improves biocompatibility by using the NO effect to promote endothelial cell (EC) migration and proliferation while preventing bacterial infection. To circumvent the instability of NO donors and to prolong NO releasing, S-nitroso-N-acetyl-D-penicillamine (SNAP) as a NO donor was loaded in multi-walled carbon nanotubes (MWCNTs). Successful loading was confirmed with a maximum SNAP amount of ~ 5% (w/w) by TEM, CHNS analysis and FTIR spectra. SDVGs were 3D printed from polycaprolactone (PCL) and coated with a 1:1 ratio of polyethylene glycol and PCL dopped with different concentrations of SNAP-loaded matrix and combinations of MWCNTs-OH. Coating with 10% (w/w) SNAP-matrix-10% (w/w) SNAP-MWCNT-OH showed a diminished burst release and 18 days of NO release in the range of 0.5-4 × 10 mol cm min similar to the NO release from healthy endothelium. NO-releasing SDVGs were cytocompatible, significantly enhanced EC proliferation and migration and diminished bacterial viability. The newly developed SNAP-loaded MWCNT-OH has a great potential to develop NO releasing biomaterials with a prolonged, controlled NO release promoting in-situ endothelialization and tissue integration in vivo, even as an approach towards personalized medicine.
Topics: Nitric Oxide; Nanotubes, Carbon; S-Nitroso-N-Acetylpenicillamine; Delayed-Action Preparations; Nitric Oxide Donors; Printing, Three-Dimensional
PubMed: 36949216
DOI: 10.1038/s41598-023-31619-3 -
Food Chemistry Aug 2023With the food safety issues abounding, exploring reliable and efficient methods for evaluating food safety is crucial. Herein, a ratiometric test strip was proposed by...
With the food safety issues abounding, exploring reliable and efficient methods for evaluating food safety is crucial. Herein, a ratiometric test strip was proposed by using green-yellow fluorescent d-penicillamine capped silver nanocluster (DPA-AgNCs) as indicator and red-emitting bimetallic gold/silver nanoclusters (AuAgNCs) as an internal reference, providing a real-time and visual monitoring system for food freshness. Results showed that the as-prepared DPA-AgNCs displayed an excellent response and good sensitivity for volatile basic nitrogens (VBNs), with a limit of detection (LOD) of 0.51 μM and 0.08 ppm for spermidine and ammonia hydroxide, respectively. Subsequently, a ratiometric test strip was developed to visually monitor ammonia vapour, displaying an obvious fluorescence colour variation from mustard to deep-red. Moreover, the presented ratiometric test strip was successfully applied for non-contact and visual evaluating and monitoring VBNs in the shrimp sample, showing high potential for in-situ monitoring.
Topics: Silver; Nitrogen; Ammonia; Coloring Agents; Penicillamine; Seafood; Fluorescent Dyes; Metal Nanoparticles; Spectrometry, Fluorescence
PubMed: 36934615
DOI: 10.1016/j.foodchem.2023.135725 -
ACS Applied Materials & Interfaces Mar 2023Biofilm formation on biomaterial interfaces and the development of antibiotic-resistant bacteria have decreased the effectiveness of traditional antibiotic treatment of...
Biofilm formation on biomaterial interfaces and the development of antibiotic-resistant bacteria have decreased the effectiveness of traditional antibiotic treatment of infections. In this project, ampicillin, a commonly used antibiotic, was conjugated with -nitroso--acetylpenicillamine (SNAP), an -nitrosothiol compound (RSNO) used for controlled nitric oxide (NO) release. This novel multifunctional molecule is the first of its kind to provide combined antibiotic and NO treatment of infectious pathogens. Characterization of the molecule included NMR, FTIR, and mass spectrometry. NO release behavior was also measured and compared to pure, unmodified SNAP. When evaluating the antimicrobial efficacy, the synthesized SNAPicillin molecule showed the lowest MIC value against Gram-negative and Gram-positive methicillin-resistant compared to ampicillin and SNAP alone. SNAPicillin also displayed enhanced biofilm dispersal and killing of both bacterial strains when treating a 48 h biofilm preformed on a polymer surface. The antibacterial results combined with the biocompatibility of the molecule show great promise for infection prevention and treatment of polymeric interfaces to reduce medical device-related infections.
Topics: Nitric Oxide; Methicillin-Resistant Staphylococcus aureus; S-Nitroso-N-Acetylpenicillamine; Anti-Bacterial Agents; Ampicillin; Bacteria; Biofilms
PubMed: 36926823
DOI: 10.1021/acsami.3c00140