Efficacy and expenses of succimer vs. d-penicillamine plus garlic in the treatment of lead poisoning: a retrospective cross-sectional study.

PURPOSE: Lead Poisoning is a major health problem in Iran. We aimed to compare efficacy of a standard regimen (Succimer) with that of a low-priced combination of D-penicillamine and Garlic in outpatients with lead poisoning. METHODS: In this retrospective cross-sectional study, year-long clinical files of outpatients with lead poisoning in two referral toxicology clinics in Mashhad, Iran were reviewed. A total of 79 patients (all men), received either Succimer or a combination of D-penicillamen plus garlic (DPN + Gar), for 19 and 30 days, respectively. Clinical and laboratory data, including blood lead level (BLL), were analyzed and treatment expanses were compared between the two regimens. RESULTS: Of 79 male patients, 42 were treated by DPN + Gar and 37 received Succimer. Mean BLL of DPN + Gar group before treatment (965.73 ± 62.54 µg/L) was higher than that of the Succimer group (827.59 ± 24.41) (p < 0.001). After treatment, BLL in both groups significantly reduced to 365.52 ± 27.61 µg/L and 337.44 ± 26.34 µg/L, respectively (p < 0.001). The price of a 19-day treatment with Succimer was approximately 28.6 times higher than a one-month course of treatment with garlic plus DPN. None of the treatments caused serious side effects in the patients. CONCLUSION: Combination therapy with DPN + Gar is as effective as Succimer in Pb poisoning, while treatment with Succimer is significantly more expensive.

Transferrin Coated d-penicillamine-Au-Cu Nanocluster PLGA Nanocomposite Reverses Hypoxia-Induced EMT and MDR of Triple-Negative Breast Cancers.

Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, lacks effective targeted therapies due to negative expression of the targetable bioreceptors. Additionally, hypoxic condition in solid tumors contributes to the epithelial to mesenchymal transition (EMT), which aggravates cancer progression, multidrug resistance (MDR), migration, and stemness of the TNBC. A therapeutic module has been established in this regard by coating PLGA nanoparticle with d-penicillamine templated Au-Cu bimetallic nanoclusters. Further, the resultant nanomaterials were coated with recombinant transferrin protein to specifically target transferrin receptor overexpressing TNBC. The synthesized nanocomposites showed strong orange emission band at 630 nm with fluorescence quantum yield of 2%, rendering it suitable for theranostic applications. Experimental results demonstrated efficient cellular internalization and significant innate anti-cell proliferative potential of the nanocomposites. The fabricated nanocomposites were also able to induce cell death in spheroids, which was confirmed by live/dead dual staining results. Furthermore, when EMT-induced TNBC cells were treated with nanocomposites, they generated reactive oxygen species (ROS), depolarized the mitochondrial membrane potential, and induced apoptosis. Gene expression by real-time PCR indicated that treatment of EMT-induced TNBC cells with nanocomposites facilitated mesenchymal to epithelial transition (MET). In MDA-MB-468 cells, treatment with nanocomposites resulted in a 1.35-fold rise in E-cadherin an epithelial marker and a 1.36-fold decrease in vimentin a mesenchymal marker. Similarly, 2.87-fold and 1.76-fold decrease in stemness markers ALDH1A3 and EpCAM were observed in MDA-MB-231. Furthermore, 4.63-fold decrease in expression of ABCC1, a prominent contributor of MDR, was observed in MDA-MB-231. Protein expression studies revealed that nanocomposites reduced p-STAT-3 by 1.61-fold in MDA-MB-231 and by 7.8-fold in MDA-MB-468. Importantly, nanocomposites downregulated the expression of ß-catenin by 3-fold in MDA-MB-231 and by 3.11-fold in MDA-MB-468. Downregulation of EMT with concomitant alteration of STAT-3 and ß-catenin signaling pathways led to reduced migration ability of the TNBC cells.

Liquid chromatography/tandem mass spectrometric analysis of penicillamine for its pharmacokinetic evaluation in dogs.

Copper storage disease occurs in multiple dog breeds and is one of the most common causes of chronic hepatitis in this species. The disease is caused by hereditary defects in copper metabolism in conjunction with high dietary copper levels. The progressive copper accumulation leads to hepatitis, cirrhosis, and eventually death if left untreated. Copper chelators are critical in modulating the effects of this disease. It is therefore of significant practicality to understand the pharmacokinetic (PK) parameters of chelating agents, particularly since they are oftentimes quite expensive. A liquid chromatography-tandem mass spectrometric (LC/MS/MS) method was developed to measure plasma levels of one of the most common chelators, d-penicillamine. The compound was discovered to exist in two forms, monomeric and dimeric, and various chemical derivatizations were tried to force the compound into one form or the other. Eventually, the simplest approach was individual determination of penicillamine and its dimer, with summation of the two quantities. This enabled determination of canine PK parameters for penicillamine based on comparison of oral and intravenous administration of the drug, including time to maximum drug level (Tmax), concentration at maximum (Cmax), clearance (Cls) and volume of distribution (Vdss). The drug was found to exist predominantly in the dimeric form in plasma, which is incapable of chelating copper owing to lack of free sulfhydryl groups and must therefore provide a storage form of the drug in equilibrium with its monomeric form in vivo. Mechanisms are discussed for the electrospray-induced fragmentation of penicillamine as well as of its dimer.

S-Nitroso-N-Pivaloyl-D-Penicillamine, a novel non-neuronal ACh system activator, modulates cardiac diastolic function to increase cardiac performance under pathophysiological conditions.

We have previously reported the development of a novel chemical compound, S-Nitroso-N-Pivaloyl-D-Penicillamine (SNPiP), for the upregulation of the non-neuronal cardiac cholinergic system (NNCCS), a cardiac acetylcholine (ACh) synthesis system, which is different from the vagus nerve releasing of ACh as a neurotransmitter. However, it remains unclear how SNPiP could influence cardiac function positively, and whether SNPiP could improve cardiac function under various pathological conditions. SNPiP-injected control mice demonstrated a gradual upregulation in diastolic function without changes in heart rate. In contrast to some parameters in cardiac function that were influenced by SNPiP 24 h or 48 h after a single intraperitoneal (IP) injection, 72 h later, end-systolic pressure, cardiac output, end-diastolic volume, stroke volume, and ejection fraction increased. IP SNPiP injection also improved impaired cardiac function, which is a characteristic feature of the db/db heart, in a delayed fashion, including diastolic and systolic function, following either several consecutive injections or a single injection. SNPiP, a novel NNCCS activator, could be applied as a therapeutic agent for the upregulation of NNCCS and as a unique tool for modulating cardiac function via improvement in diastolic function.

Adjunctive Antioxidant Therapy in Neurologic Wilson's Disease Improves the Outcomes.

Oxidative stress has been reported in Wilson's disease with neurological manifestation (WDNM), but there is a paucity of studies on the role of adjunctive antioxidant therapy. This study aims to evaluate the efficacy of adjunctive vitamin C and E treatment in reducing oxidative stress and improving clinical outcomes. Forty-nine patients with WDNM were included and their clinical details were noted. Glutathione (GSH), total antioxidant capacity (TAC), and malondialdehyde (MDA) were measured using spectrophotometer at baseline and follow-up. All patients received zinc with or without chelating therapy, and 32 of them prescribed vitamin C (500 mg/day) and E (400 mg/day). Clinical outcomes at 6, 12, and 24 months were categorized as improved, static, or worsened based on improvement in Burke-Fahn-Marsden (BFM) score (>10%) and/or severity grade (> 1). Baseline parameters were similar between two groups; except BFM score was higher in the antioxidant group. At follow-up, the antioxidant group had higher GSH, TAC, and lower MDA levels compared with baseline. Patients on antioxidant treatment experienced improvement more frequently at 6 (53.1% vs. 29.4%), 12 (62.5% vs. 29.4%), and 24 months (68.8% vs. 35.3%) compared with those without antioxidant treatment. In WDNM, adjunctive vitamin C and E treatment reduce oxidative stress and improve clinical outcome.

[Diagnosis and treatment of Wilson disease in Japan].

Wilson disease is an autosomal recessive disorder based on inborn error of copper metabolism. The copper accumulates in the liver, brain, cornea, kidney, and other organs. This disease should be considered any individual with liver abnormality except infant, any patient older than teenage with neurological (especially for extra pyramidal signs) or neuropsychiatric disorder with or without liver disease and sibling of Wilson disease patient. Typically, a combination of low serum ceruloplasmine levels and high levels of urinary copper contents is sufficient to establish a diagnosis. As other diagnostic tests, measurement of hepatic copper content and ATP7B gene analysis are available. The key strategy of treatment is to reduce the amount of copper in the liver and other tissues by administering both copper-chelating agents, such as D-penicillamine or Trientine, and/or zinc acetate. The author recommend zinc acetate monotherapy for mild to moderate hepatic disorder, Trientine mono therapy for mild to moderate neurologic disorder and combination therapy of Trientine and zinc acetate for sever hepatic or neurologic disorder.

Treatment of adult lead poisoning with D-penicillamine.

Background The aim of the current study was to evaluate the efficacy of D-penicillamine in the treatment of lead poisoning mainly in the outpatient setting. Methods In a case series study performed during the recent epidemic of lead poisoning in Iran, lead-poisoned patients referring to our outpatient clinic were treated with 250-mg D-penicillamine capsules administered every 6 h for 5 or 10 days based on availability of the medication. They were recommended to re-check blood lead level (BLL) 4 weeks after cessation of the treatment and refer to our clinic again. Results In 63 patients with lead poisoning but without signs and symptoms of lead encephalopathy, median BLL was 106 [84, 131] µg/dL on presentation, which declined to a mean of 52.6 ± 28.8 µg/dL after a median treatment period of 7 [5, 10] days (p < 0.001). There was no statistically significant difference between the 5- and 10-day treatment protocols regarding complications and recovery. Treatment had resulted in a median decrease of 54 µg/dL [33, 90] (range: -20 to 231 µg/dL) in the patients' BLLs (33.9% declined in BLL measurements; range: -29.69% to 99.06%). Conclusions D-penicillamine may be an acceptable substitute treatment in adult lead poisoning. Although our sample size was limited, we could not detect any serious adverse effects in our cases showing that D-penicillamine resulted in acceptable recovery rates. This may be helpful especially in epidemics with limitations in antidote access.

Effect of increasing doses of cystine-binding thiol drugs on cystine capacity in patients with cystinuria.

Appropriate dosing of cystine-binding thiol drugs in the management of cystinuria has been based on clinical stone activity. When new stones form, the dose is increased. Currently, there is no method of measuring urinary drug levels to guide the titration of therapy. Increasing cystine capacity, a measure of cystine solubility, has been promoted as a method of judging the effects of therapy. In this study, we gave increasing doses of tiopronin or D-penicillamine, depending on the patients' own prescriptions, to ten patients with cystinuria and measured cystine excretion and cystine capacity. The doses were 0, 1, 2, 3 g per day, given in two divided doses, and administered in a random order. Going from 0 to 1 g/day led to an increase in cystine capacity from - 39.1 to 130.4 mg/L (P < 0.009) and decreased 24 h cystine excretion from 1003.9 to 834.8 mg/day (P = 0.039). Increasing the doses from 1 to 2 to 3 g/day had no consistent or significant effect to further increase cystine capacity or decrease cystine excretion. Whether doses higher than 1 g/day have additional clinical benefit is not clear from this study. Limiting doses might be associated with fewer adverse effects without sacrificing the benefit of higher doses if higher doses do not offer clinical importance. However, trials with stone activity as an outcome would be desirable.

A case report: Co-occurrence of Wilson disease and oculocutaneous albinism in a Chinese patient.

RATIONALE: Both Wilson disease (WD) and Oculocutaneous Albinism (OCA) are rare autosomal recessive disorders that are caused by mutations on chromosome 13 and chromosome 11, respectively. Here, we report on a patient with coexisting WD and OCA, initially presenting episodes of tremors. PATIENT CONCERNS: WD is a disorder of copper metabolism. The main sites of copper accumulation are the liver and the brain, resulting in hepatic symptoms. OCA is a disorder of melanin biosynthesis, characterized by a generalized reduction in pigmentation of the eyes (oculo-), skin (-cutaneous), and hair. DIAGNOSIS: The diagnosis of WD was confirmed by neurological symptoms, metabolism tests, and MRI scans. Interestingly, the patient also had very light skin color, blond hair and eyebrows, and dark brown eyelashes and irises. Because the association of dermatologic signs in WD has rarely been reported, OCA was highly suspected based on these clinical findings. Genetic analysis was subsequently conducted, and the results revealed the p. (Arg778Leu) mutation in 1 allele and the p. (Asn1270Ser) mutation in the other allele of the ATP7B gene, confirming the diagnosis of WD; the p. (D456fs) mutation in 1 allele and the p. (R299H) mutation in the other allele of the TYR gene, confirming the diagnosis of OCA. The family history was positive for WD with a 14-year-old younger brother also being diagnosed with it. Her parents are negative for OCA and WD. INTERVENTIONS: Sodium dimercaptopropanesulfonate (DMPS) was given during hospitalization. D-penicillamine and zinc sulfate treatment was initiated after discharge for long-term control. OUTCOMES: Postural and intention tremor disappeared, and other symptoms and signs markedly improved after treatment. LESSONS: In this study, we reported on the first case of a child who simultaneously presented WD and OCA, bringing up the possibility of a presumable link between these 2 rare diseases.

Hepatic manifestations of Wilson's disease: 12-year experience in a Swiss tertiary referral centre.

BACKGROUND AND AIM: Wilson’s disease is an inherited disorder of hepatic copper metabolism, leading to the accumulation of copper in the liver as well as the brain, cornea and other organs. Here, we describe the adult cases of hepatic Wilson’s disease diagnosed at the Division of Gastroenterology and Hepatology of the University Hospital Lausanne, Switzerland between September 2004 and August 2016. METHODS: Clinical manifestations, results of diagnostic tests, management and outcomes of adult patients with hepatic Wilson’s disease were assessed based on standardised medical records. In addition, liver histology was reviewed and the lesional patterns were recorded. RESULTS: Ten new adult cases of hepatic Wilson’s disease were diagnosed in our centre between September 2004 and August 2016. Male to female ratio was 1:1 and median age at diagnosis was 26 (range 18–56) years. Four patients presented with acute liver failure, four with persistently elevated liver function tests, and two with decompensated cirrhosis; none had neurological manifestations. Only one patient had a Kayser-Fleischer corneal ring. Median ceruloplasmin level at diagnosis was 0.13 (range <0.03–0.30) g/l, median 24-hour urinary copper excretion was 2.8 (range 0.3–77.3) μmol, and median hepatic copper concentration was 789 (range 284–1677) μg/g. At least one mutation in the ATP7B gene was identified in eight patients. Allelic frequency of the common H1069Q mutation was 19%. Leipzig score was ≥5 in all patients. Three patients presenting with acute liver failure and the two with decompensated cirrhosis underwent successful liver transplantation. One patient with acute liver failure recovered under chelation therapy, as predicted by a Dhawan score <11. D-penicillamine was used as first-line chelator treatment, with a subsequent switch to trientine due to adverse effects in three out of six patients. CONCLUSIONS: The clinical presentation of hepatic Wilson’s disease is highly variable. Three out of 10 patients were diagnosed at an age >35 years. A high index of suspicion in clinically compatible situations is key.

GanDouLing combined with Penicillamine improves cerebrovascular injury via PERK/eIF2α/CHOP endoplasmic reticulum stress pathway in the mouse model of Wilson's disease.

We aim to investigate the function and mechanism of GanDouLing combinated with Penicillamine on cerebrovascular injury in Wilson's disease (WD). ELISA was performed to analyze the expression of vascular injury factors. Pathological changes of cerebral vessels were observed by HE stain. Immunohistochemistry assays were performed to analyze the expression of ICAM-1, VCAM-1, and GRP78. Western blotting was measured to analyze the expression of caspase-3, caspase-12, PERK, eIF2α, and CHOP. Apoptosis was detected with TUNEL assay. The expression of vascular injury factors and ICAM-1, VCAM-1 was significantly increased by WD and markedly decreased in GanDouLing-Penicillamine group. The expression of caspase-3, caspase-12, PERK, eIF2α, and CHOP were obviously expressed in Wilson group, GanDouLing-Penicillamine suppressed apoptosis and endoplasmic reticulum (ER) stress. Our findings suggested that GanDouLing-Penicillamine improved cerebrovascular injury through PERK/eIF2α/CHOP ER stress pathway in the mouse model of WD.

Epigenetic changes of the thioredoxin system in the tx-j mouse model and in patients with Wilson disease.

Wilson disease (WD) is caused by mutations in the copper transporter ATP7B, leading to copper accumulation in the liver and brain. Excess copper inhibits S-adenosyl-L-homocysteine hydrolase, leading to variable WD phenotypes from widespread alterations in DNA methylation and gene expression. Previously, we demonstrated that maternal choline supplementation in the Jackson toxic milk (tx-j) mouse model of WD corrected higher thioredoxin 1 (TNX1) transcript levels in fetal liver. Here, we investigated the effect of maternal choline supplementation on genome-wide DNA methylation patterns in tx-j fetal liver by whole-genome bisulfite sequencing (WGBS). Tx-j Atp7b genotype-dependent differences in DNA methylation were corrected by choline for genes including, but not exclusive to, oxidative stress pathways. To examine phenotypic effects of postnatal choline supplementation, tx-j mice were randomized to one of six treatment groups: with or without maternal and/or continued choline supplementation, and with or without copper chelation with penicillamine (PCA) treatment. Hepatic transcript levels of TXN1 and peroxiredoxin 1 (Prdx1) were significantly higher in mice receiving maternal and continued choline with or without PCA treatment compared to untreated mice. A WGBS comparison of human WD liver and tx-j mouse liver demonstrated a significant overlap of differentially methylated genes associated with ATP7B deficiency. Further, eight genes in the thioredoxin (TXN) pathway were differentially methylated in human WD liver samples. In summary, Atp7b deficiency and choline supplementation have a genome-wide impact, including on TXN system-related genes, in tx-j mice. These findings could explain the variability of WD phenotype and suggest new complementary treatment options for WD.

Maintenance zinc therapy after initial penicillamine chelation to treat symptomatic hepatic Wilson's disease in resource constrained setting.

BACKGROUND: Experience with zinc in treating symptomatic hepatic Wilson's disease (WD) is limited. AIM: To study the efficacy of Penicillamine followed by zinc in treating symptomatic hepatic Wilson's disease. METHODS: We retrospectively analyzed case records of 31 symptomatic hepatic WD patients for whom disease severity scores (Child's, model for end-stage liver disease (MELD), Nazer's, and New Wilson Index (NWI) score) and 24-h urinary copper were compared at 3-time points-baseline at presentation, at transition from penicillamine to zinc and at end of follow up. RESULTS: Thirty-one patients (median age 11 [5-24] years) with symptomatic hepatic WD were studied; ten had associated neuropsychiatric manifestations of WD. Penicillamine was changed to zinc sulfate either due to financial constraints (28 patients) or due to adverse effects of penicillamine (3 patients). At presentation (baseline), six patients belonged to Child's class A, five to Child's B, and 17 to Child's C. Duration of initial penicillamine chelation therapy was 134 (2-320) weeks, and of subsequent zinc therapy was 363 (35-728) weeks. There was a significant improvement in liver function tests and disease severity scores (Child's, MELD, Nazer's, and NWI score) at the transition from penicillamine to zinc compared to baseline. This improvement was maintained until the end of study period with 90% survival at 10 (2-20) years. Fifteen of the 17 Child's C cirrhotic patients showed significant improvement in disease severity scores from baseline until end of follow up. CONCLUSIONS: Penicillamine followed by zinc may be a safe and effective treatment in resource-constrained setting for symptomatic hepatic WD patients in all grades of baseline disease severity. Some patients with decompensated cirrhosis due to WD may be managed with medical treatment, avoiding liver transplantation.

Childhood Wilson Disease: Bangladesh Perspective.

Wilson's disease (WD) is an autosomal recessive disorder affecting copper metabolism causing copper induced damage to various organs. In children liver is commonly involved. Central nervous system, eyes, RBC, kidneys, brain and bones may also be affected. Aim of the study is to evaluate clinical & laboratory profile of Wilson's disease in children. This cross sectional descriptive study was conducted at the department of Paediatric Gastroenterology and Nutrition, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, from January 2011 to December, 2013. One hundred consecutive children of WD between 3 to 18 years of age were evaluated for clinical & biochemical profile. Mean age of studied children was 8.5±1.5 years. Male female ratio was 2:1. Ninety one percent patients were Muslim and nine percent Hindu. Consanguinity of marriage was found in 30% cases. Seven parents were first degree cousin. Family history of chronic liver disease was present in 15% of patients. Most (53%) cases of the hepatic WD presented between 5 to 10 years of age and most of the neurologic WD manifested in 10-15 years age group. Among 100 patients of WD, 69 children presented only with hepatic manifestations, 6 only with neurological manifestations, 14 with both hepatic & neurological manifestation, 10 children was asymptomatic and 1 patient presented with psychiatric features. WD presented as chronic liver disease (CLD) in 42%, CLD with portal hypertension in 34%, acute hepatitis in 20% and fulminant hepatic failure in 4% cases. Stigmata of chronic liver disease were found in 18% patients. Commonest stigmata was thenar and hypothenar wasting (n=8). Keiser- Fleischser ring (K-F ring) was found in 76% of the total patients. K-F ring was present in 84% ( 58 out of 69) of the hepatic only Wilsonian patients and in 90% (18 out of 20) of all neurologic Wilsonian patients. Asymptomatic and psychiatric patient had no K-F ring. About 26% of the WD patients had Coombs negative hemolytic anemia in PBF. Most of the WD patients had altered liver function. Elevated serum transaminase was found in 85% of all cases, prolonged prothrombin time in 59% cases & low serum albumin in 53% cases. Seventy three percent patients had low serum ceruloplasmin, basal urinary copper of >100µgm/day was found in 81% cases and urinary copper following penicillamine challenge of >1200µgm/day was found in 92% cases. In 28 cases with hepatic presentation esophageal varices were identified by upper gastrointestinal endoscopy. WD patient with hepatic presentations were given zinc sulphate along with penicillamine. All patients with neurological manifestation as well as asymptomatic cases were maintained on zinc therapy. WD is a treatable metabolic cause of liver disease. Majority of studied WD children presented with hepatic manifestation of which 76% presented with CLD. Any child presented with jaundice after the age of 3 years should be investigated for WD.

A clinical study of bone mesenchymal stem cells for the treatment of hepatic fibrosis induced by hepatolenticular degeneration.

The efficacy of bone marrow mesenchymal stem cell (BMSC) on liver fibrosis in animal has been proven, but a few studies have been made in human body and few such researches in China. This study was designed to investigate the effect of BMSC treatment on hepatic fibrosis induced by hepatolenticular degeneration and the influence on serological indicators. Sixty patients with liver fibrosis induced by hepatolenticular degeneration were randomly divided into two groups, a penicillamine group and a BMSCs plus penicillamine group, with 30 patients in each. The therapeutic effects on hepatic fibrosis, liver function, and serological indicators were recorded before and after the treatment, and the data were compared. After treatment, serum levels of HA, PCIII, LN, CIV, TIMP-1, and MMP-1 were reduced in both groups (P < 0.05). However, cytokine levels in the BMSCs plus penicillamine group were significantly lower than those in the penicillamine group (P < 0.05). Combination therapy with BMSCs and penicillamine had a significant positive effect on liver fibrosis induced by hepatolenticular degeneration.

Wilson Disease: Epigenetic effects of choline supplementation on phenotype and clinical course in a mouse model.

Wilson disease (WD), a genetic disorder affecting copper transport, is characterized by hepatic and neurological manifestations with variable and often unpredictable presentation. Global DNA methylation in liver was previously modified by dietary choline in tx-j mice, a spontaneous mutant model of WD. We therefore hypothesized that the WD phenotype and hepatic gene expression of tx-j offspring could be modified by maternal methyl supplementation during pregnancy. In an initial experiment, female tx-j mice or wild type mice were fed control or choline-supplemented diets 2 weeks prior to mating through embryonic day 17. Transcriptomic analysis (RNA-seq) on embryonic livers revealed tx-j-specific differences in genes related to oxidative phosphorylation, mitochondrial dysfunction, and the neurological disorders Huntington's disease and Alzheimer disease. Maternal choline supplementation restored the transcript levels of a subset of genes to wild type levels. In a separate experiment, a group of tx-j offspring continued to receive choline-supplemented or control diets, with or without the copper chelator penicillamine (PCA) for 12 weeks until 24 weeks of age. Combined choline supplementation and PCA treatment of 24-week-old tx-j mice was associated with increased liver transcript levels of methionine metabolism and oxidative phosphorylation-related genes. Sex differences in gene expression within each treatment group were also observed. These results demonstrate that the transcriptional changes in oxidative phosphorylation and methionine metabolism genes in WD that originate during fetal life are, in part, prevented by prenatal maternal choline supplementation, a finding with potential relevance to preventive treatments of WD.

Radiolabeled D-Penicillamine Magnetic Nanocarriers for Targeted Purposes.

The aim of this study is to synthesize D-Penicillamine (D-PA) conjugated magnetic nanocarriers for targeted purposes. Magnetic nanoparticles were prepared by partial reduction method and surface modification was done with an amino silane coupling agent's (structural properties), AEAPS, the particles were characterized by Scanning Electron Microscope (SEM), X-ray Diffraction (XRD). After that D-PA was linked with the magnetic nanoparticles (MNPs) and has been radiolabeled with [99mTc(CO)3]+ core. Quality controls of [99mTc(CO)3-MNP-D-PA] were established by Cd(Te) detector. The radiolabeling efficiency of magnetic nanoparticles ([99mTc(CO)3-MNP-D-PA]) was about 97.05% with good in vitro stability during the 24 hour period. As a parallel study, radiolabeled D-PA complex ([99mTc(CO)3-D-PA]) was prepared with a radiolabeling yield of 97.93%. At the end, biologic activities of binding complexes were investigated on MCF7 human breast cancer cells. Our results show that, radiolabeled magnetic nanoparticles with core [99mTc(CO)3]+ ([99mTc(CO)3-MNP-D-PA]) showed the highest uptake on MCF7 cells which were applied magnetic field in the wells. In that case, result of this study emphasizes that radiolabeled magnetic nanoparticles with core [99mTc(CO)3]+ would support new occurrences of new agents.