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1.
FASEB J ; 38(4): e23476, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38334392

ABSTRACT

The prevalence of alopecia has increased recently. Hair loss is often accompanied by the resting phase of hair follicles (HFs). Dermal papilla (DP) plays a crucial role in HF development, growth, and regeneration. Activating DP can revive resting HFs. Augmenting WNT/ß-catenin signaling stimulates HF growth. However, the factors responsible for activating resting HFs effectively are unclear. In this study, we investigated epidermal cytokines that can activate resting HFs effectively. We overexpressed ß-catenin in both in vivo and in vitro models to observe its effects on resting HFs. Then, we screened potential epidermal cytokines from GEO DATASETs and assessed their functions using mice models and skin-derived precursors (SKPs). Finally, we explored the molecular mechanism underlying the action of the identified cytokine. The results showed that activation of WNT/ß-catenin in the epidermis prompted telogen-anagen transition. Keratinocytes infected with Ctnnb1-overexpressing lentivirus enhanced SKP expansion. Subsequently, we identified endothelin 1 (ET-1) expressed higher in hair-growing epidermis and induced the proliferation of DP cells and activates telogen-phase HFs in vivo. Moreover, ET-1 promotes the proliferation and stemness of SKPs. Western blot analysis and in vivo experiments revealed that ET-1 induces the transition from telogen-to-anagen phase by upregulating the PI3K/AKT pathway. These findings highlight the potential of ET-1 as a promising cytokine for HF activation and the treatment of hair loss.


Subject(s)
Hair Follicle , Proto-Oncogene Proteins c-akt , Animals , Mice , Hair Follicle/metabolism , Proto-Oncogene Proteins c-akt/metabolism , beta Catenin/genetics , beta Catenin/metabolism , Endothelin-1/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Cells, Cultured , Cell Proliferation , Epidermis/metabolism , Alopecia/metabolism , Wnt Signaling Pathway , Dermis/metabolism , Cytokines/metabolism
2.
Inorg Chem ; 63(1): 474-484, 2024 Jan 08.
Article in English | MEDLINE | ID: mdl-38100511

ABSTRACT

It is of great significance to develop efficient methods for preparing high-content modified nanoscale lead azide (LA) composites used in microinitiating devices. In this work, a structurally controllable salicylate-intercalated lead hydroxide with a nanoscale mesoporous structure is designed. Using it as a precursor, carbon-based lead azide (LA/C) and salicylate-based lead azide (LA/SA) are fabricated by the gas-solid azidation of the framework (GAF) method within 3 h, greatly reducing the preparation time of nano-LA composites. The characterizations of the composites demonstrate that the Pb in the precursors is transformed into nanoscale LA attached to the salicylate radical or its carbonized skeleton. Due to the unique embedded nanostructures and excellent electrical and thermal conductivity of salicylate-derived carbon materials, LA/C exhibits excellent electrostatic safety (E50 = 0.25 J) and flame sensitivity (H50 = 28 cm). The adjustable organic-inorganic ratio of intercalated hydroxides allows the LA content in LA/C to reach as high as 92.5%, enabling 6.50 mg of LA/C to successfully detonate secondary explosive CL-20 in a microinitiating device, demonstrating an amazing detonation ability superior to other reported LA complexes. The research provides a new perspective for the development of nanoscale LA composites with high LA content and appropriate sensitivity.

3.
J Am Chem Soc ; 145(20): 10991-10997, 2023 May 24.
Article in English | MEDLINE | ID: mdl-37186951

ABSTRACT

Herein we disclose a strategy to promote the hydrocarboxylation of unactivated alkenes using photochemical activation of formate salts. We illustrate that an alternative initiation mechanism circumvents the limitations of prior approaches and enables hydrocarboxylation of this challenging substrate class. Specifically, we found that accessing the requisite thiyl radical initiator without an exogenous chromophore eliminates major byproducts that have plagued attempts to exploit similar reactivity for unactivated alkene substrates. This redox-neutral method is technically simple to execute and effective across a broad range of alkene substrates. Feedstock alkenes, such as ethylene, are hydrocarboxylated at ambient temperature and pressure. A series of radical cyclization experiments indicate how the reactivity described in this report can be diverted by more complex radical processes.

4.
Biochem Biophys Res Commun ; 683: 149117, 2023 11 26.
Article in English | MEDLINE | ID: mdl-37857166

ABSTRACT

The progression and spread of tumors are believed to be primarily caused by cancer stem cells (CSCs). Nevertheless, the task of focusing on CSCs for cancer treatment continues to be difficult. Lgr5, a G-protein-coupled receptor containing leucine-rich repeats, is highly expressed in different types of cancer and serves as a distinctive marker for cancer stem cells (CSCs). In this study, we employed the Cre-loxP system and Lgr5 tracking mice of male to selectively remove PTEN and ß-catenin in Lgr5+ cells of DEN-induced liver cancer and monitor the behavior of Lgr5+ cells. The tracking data revealed that the activation of PTEN-mediated AKT signaling in Lgr5 led to a significant rise in the quantity of Lgr5+ cells, whereas the inhibition of Wnt/ß-catenin signaling decreased the number of cells in DEN-induced liver cancer. Therefore, we have shown that the growth of Lgr5+ cells can be controlled by the PTEN/AKT and Wnt/ß-catenin pathways, offering a potential treatment option for fighting against liver cancer.


Subject(s)
Liver Neoplasms , Wnt Signaling Pathway , Male , Animals , Mice , Proto-Oncogene Proteins c-akt/metabolism , beta Catenin/metabolism , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Neoplastic Stem Cells/pathology , Cell Proliferation , Liver Neoplasms/pathology
5.
Mar Drugs ; 21(6)2023 May 26.
Article in English | MEDLINE | ID: mdl-37367653

ABSTRACT

In this study, we characterized the bioactive properties of three important brown seaweed species, Sargassum thunbergii, Undaria pinnatifida, and Saccharina japonica, by subcritical water extraction (SWE), as these species are well known for their beneficial health effects. Their physiochemical properties, including potential antioxidant, antihypertensive, and α-glucosidase inhibitory activity, and the antibacterial activity of the hydroysates were also analyzed. The highest total phlorotannin, total sugar content, and reducing sugar content in the S. thunbergii hydrolysates were 38.82 ± 0.17 mg PGE/g, 116.66 ± 0.19 mg glucose/g dry sample, and 53.27 ± 1.57 mg glucose/g dry sample, respectively. The highest ABTS+ and DPPH antioxidant activities were obtained in the S. japonica hydrolysates (124.77 ± 2.47 and 46.35 ± 0.01 mg Trolox equivalent/g, respectively) and the highest FRAP activity was obtained in the S. thunbergii hydrolysates (34.47 ± 0.49 mg Trolox equivalent/g seaweed). In addition, the seaweed extracts showed antihypertensive (≤59.77 ± 0.14%) and α-glucosidase inhibitory activity (≤68.05 ± 1.15%), as well as activity against foodborne pathogens. The present findings provide evidence of the biological activity of brown seaweed extracts for potential application in the food, pharmaceutical, and cosmetic sectors.


Subject(s)
Seaweed , Water , Water/chemistry , alpha-Glucosidases , Antioxidants/chemistry , Antihypertensive Agents/analysis , Seaweed/chemistry , Glucose , Plant Extracts/pharmacology
6.
Medicina (Kaunas) ; 59(3)2023 Mar 07.
Article in English | MEDLINE | ID: mdl-36984520

ABSTRACT

Background and Objectives: Opioid use in Korea is lower than in other developed countries. However, recent studies have reported an increase in opioid prescriptions and the number of chronic opioid users. The current status of adverse events (AEs) associated with opioid analgesics in Korea is unclear. This nested case-control study aimed to evaluate the influence of opioid analgesic use patterns on all emergency department (ED) visits and opioid-related ED visits after opioid analgesic initiation using the national claims database. Materials and Methods: Adult non-cancer patients who initiated non-injectable opioid analgesics (NIOA) between January 2017 and June 2018 were included. We defined the case group as patients who visited the ED within six months of opioid initiation, and the control group was selected in a 1:1 ratio using an exact matching method. Results: A total of 97,735 patients (13.58%) visited the ED within six months of NIOA initiation. Nearly 32% of cases were linked to opioid-related AEs. The most frequent AEs were falls and fractures (61.27%). After adjusting for covariates, opioid initiation at the ED was associated with all-cause or opioid-related ED visits (adjusted odds ratio (aOR) = 3.19, 95% confidence interval (CI) = 3.09-3.29; aOR = 3.82, 95% CI = 3.62-4.04, respectively). Chronic NIOA use was associated with all-cause and opioid-related ED visits (aOR = 1.32, 95% CI = 1.23-1.40; aOR = 1.56, 95% CI = 1.39-1.76, respectively). Conclusion: This study found that 13% of non-cancer patients visited the ED within six months of NIOA initiation. In addition, the NIOA use pattern was significantly associated with all-cause and opioid-related ED visits.


Subject(s)
Analgesics, Non-Narcotic , Analgesics, Opioid , Adult , Humans , Analgesics, Opioid/adverse effects , Case-Control Studies , Risk Factors , Emergency Service, Hospital , Republic of Korea/epidemiology
7.
Medicina (Kaunas) ; 59(1)2023 Jan 12.
Article in English | MEDLINE | ID: mdl-36676775

ABSTRACT

Background and objectives: We aimed to describe medication-related incidents or medication errors (MEs) reported by community pharmacists and analyze the prevalent medications involved. Materials and Methods: We extracted ME reports from databases comprising patient safety incidents reported to the Korean Pharmaceutical Association between January 2013 and June 2021. Medications were analyzed according to the second (therapeutic subgroup) and fifth (chemical substance) levels of the Anatomical Therapeutic Chemical classification. Results: A total of 9046 MEs were identified, most of which were near miss reports (88.3%). Among the errors that reached the patients (521 cases), harmful incidents accounted for 76.8%. Most MEs occurred during prescription (89.5%), while harmful MEs occurred mainly during dispensing (73.3%). In the prescription step, wrong drugs (44.8%), dosing errors (27.0%), and wrong durations (14.0%) were common. Anti-inflammatory and anti-rheumatic products (M01), drugs for acid-related disorders (A02), and antihistamines for systemic use (R06) were the most frequently reported medication classes involved. Harmful incidents were most common for dosing errors (31.0%) and wrong drugs (26.8%) and were common with warfarin, levothyroxine, and glimepiride. Conclusions: The MEs reported by community pharmacists were mainly prescribing errors, most of which were rectified before reaching patients. The prevalent medications involved in harmful errors include anti-diabetic, anti-thrombotic, and anti-inflammatory agents.


Subject(s)
Medication Errors , Pharmacists , Humans , Cross-Sectional Studies , Patient Safety , Republic of Korea
8.
Inorg Chem ; 61(24): 9096-9103, 2022 Jun 20.
Article in English | MEDLINE | ID: mdl-35670700

ABSTRACT

Copper azide (CA) is one of the preferred primary explosives in the micro-initiating device, and it is of conducive significance to develop high-content CA-modified materials. In this work, we reported two types of CA composites with CA nanorods embedded in carbon nanosheets (CA/C) and CA distributed on salicylic acid (CA/SA) using layered copper hydroxide nanosheets intercalated with salicylic acid as the precursor. The detailed characterizations demonstrated that CA/C exhibits eximious electrostatic sensitivity (1.06 mJ) due to the inherent structural characteristics of CA/C such as the limitation of the free movement of CA by the layered structure and preeminent electrical conductivity of carbon nanosheets. Surprisingly, CA/C with nearly 1.0 mg in the miro-initiating device can reliably detonate Hexanitrohexaazaisowurtzitane (CL-20). CA/C exhibits extremely high CA content (93%), excellent ignition ability, and detonation ability, and its performance is superior to pure CA and most CA-modified materials reported previously. CA/SA also has an excellent detonation ability and its electrostatic sensitivity is as low as 0.92 mJ. These findings provide a new perspective for the development of high-performance primary explosives for the micro-initiating device.

9.
Medicina (Kaunas) ; 58(8)2022 Aug 20.
Article in English | MEDLINE | ID: mdl-36013598

ABSTRACT

Background and Objectives: Acute peripancreatic fluid collection (APFC) is an acute local complication of acute pancreatitis (AP) according to the revised Atlanta classification. Sometimes APFC resolves completely, sometimes it changes into a pseudocyst or walled-off necrosis (WON), so called late complications. The aim of this study is to investigate the natural course of APFC detected on early computed tomography (CT) in moderately severe (MSAP) or severe AP (SAP). Materials and Methods: From October 2014 to September 2015, patients with MSAP or SAP were enrolled if there was APFC within 48 h of onset on imaging studies at six medical centers. The status of fluid collection was followed 4-8 weeks after onset. Initial laboratory findings, CT findings and clinical scoring systems were analyzed. Results: A total of 68 patients were enrolled and APFC was completely resolved in 32 (66.7%) patients in the MSAP group and 9 (34.6%) in the SAP group. Patients with a high bedside index for severity in acute pancreatitis (BISAP) score (≥3 points) were common in the SAP group. C-reactive protein (CRP) after 48 h from admission and BUN level were also high in the SAP group. In multivariate analysis, BISAP score (≥3 points), elevation of CRP after 48 h (≥150 mg/L) and nasojejunal feeding after 48 h were risk factors for the development of late complications. Conclusions: Spontaneous resolution of APFC was more common in MSAP group and APFC can be changed to pseudocyst or WON in patients with elevated BISAP score, CRP level after 48 h, and non-improved abdominal pain.


Subject(s)
Pancreatitis , Acute Disease , C-Reactive Protein/metabolism , Hospitalization , Humans , Necrosis , Pancreatitis/complications , Pancreatitis/diagnosis , Severity of Illness Index
10.
Pancreatology ; 21(1): 208-214, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33281058

ABSTRACT

BACKGROUND: Pancreatic neuroendocrine neoplasms (PNENs) show heterogeneous biological behavior, and most small PNENs show indolent features. Consequently, selected cases can be considered for observation only, according to the National Comprehensive Cancer Network guideline, however, supporting clinical evidence is lacking. We investigated the clinical course of small PNENs and their risk factors for malignant potential. METHODS: A total of 158 patients with small pathologically confirmed PNENs ≤2 cm in initial imaging were retrospectively enrolled from 14 institutions. The primary outcome was any metastasis or recurrence event during follow-up. RESULTS: The median age was 57 years (range, 22-82 years), and 86 patients (54%) were female. The median tumor size at initial diagnosis was 13 mm (range, 7-20 mm). PNENs were pathologically confirmed by surgery in 137 patients and by EUS-guided fine needle aspiration biopsy (EUS-FNAB) in 21 patients. Eight patients underwent EUS-FNAB followed by surgical resection. The results of WHO grade were available in 150 patients, and revealed 123 grade 1, 25 grade 2, and 2 neuroendocrine carcinomas. A total of 145 patients (92%) underwent surgical resection, and three patients had regional lymph node metastasis. During the entire follow-up of median 45.6 months, 11 metastases or recurrences (7%) occurred. WHO grade 2 (HR 13.97, 95% CI 2.60-75.03, p = 0.002) was the only predictive factor for malignant potential in multivariable analysis. CONCLUSIONS: WHO grade is responsible for the malignant potential of small PNENs ≤2 cm. Thus, EUS-FNAB could be recommended in order to provide early treatment strategies of small PNENs.


Subject(s)
Neuroendocrine Tumors/epidemiology , Neuroendocrine Tumors/pathology , Pancreatic Neoplasms/epidemiology , Pancreatic Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Biopsy, Fine-Needle , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Lymphatic Metastasis , Male , Middle Aged , Neuroendocrine Tumors/surgery , Pancreatectomy , Pancreatic Neoplasms/surgery , Progression-Free Survival , Republic of Korea/epidemiology , Surveys and Questionnaires , Young Adult
11.
Nanotechnology ; 32(38)2021 Jun 29.
Article in English | MEDLINE | ID: mdl-34185025

ABSTRACT

In the wake of the development of micro-initiation systems, traditional lead-based primary explosives hardly satisfy the needs of high energy output. Copper azide (CA), one of the most promising primary explosives, is restricted in practical applications because of its high electrostatic sensitivity and the method of charge in micro-initiation systems. To tackle these issues, two synthetic paths of CA based on a porous graphene skeleton are proposed. First, a viscous homogeneous mixed solution is rapidly frozen in liquid nitrogen to form a spherical copper-containing precursor material. The copper azide/carbon/graphene composite (CA/C/GA) was fabricated by freeze-drying, high-temperature thermal decomposition andin situazidation. Second, A cylindrical copper/graphene gel formed by high-temperature hydrothermal self-assembly is served as a precursor material. Also, hydrogen reduction andin situazidation procedures were utilized to synthesize copper azide@graphene foam (CA@GF). Detailed characterization indicates that the excellent performance of composite materials is ascribed to the excellent electrical and thermal conductivity of graphene material. The electrostatic sensitivities of CA/C/GA and CA@GF were 3.6 mJ and 2.5 mJ, respectively, and the flame sensitivity was 50 cm. The course of fabrication is environmentally friendly and easy to perform and it may be well-matched with the charge of the micro-detonation system.

12.
Molecules ; 26(11)2021 May 31.
Article in English | MEDLINE | ID: mdl-34072626

ABSTRACT

Background: Although nilotinib hepatotoxicity can cause severe clinical conditions and may alter treatment plans, risk factors affecting nilotinib-induced hepatotoxicity have not been investigated. This study aimed to elucidate the factors affecting nilotinib-induced hepatotoxicity. Methods: This retrospective cohort study was performed on patients using nilotinib from July of 2015 to June of 2020. We estimated the odds ratio and adjusted odds ratio from univariate and multivariate analyses, respectively. Several machine learning models were developed to predict risk factors of hepatotoxicity occurrence. The area under the curve (AUC) was analyzed to assess clinical performance. Results: Among 353 patients, the rate of patients with grade I or higher hepatotoxicity after nilotinib administration was 40.8%. Male patients and patients who received nilotinib at a dose of ≥300 mg had a 2.3-fold and a 3.5-fold increased risk for hepatotoxicity compared to female patients and compared with those who received <300 mg, respectively. H2 blocker use decreased hepatotoxicity by 11.6-fold. The area under the curve (AUC) values of machine learning methods ranged between 0.61-0.65 in this study. Conclusion: This study suggests that the use of H2 blockers was a reduced risk of nilotinib-induced hepatotoxicity, whereas male gender and a high dose were associated with increased hepatotoxicity.


Subject(s)
Liver/drug effects , Machine Learning , Pyrimidines/adverse effects , Risk Assessment/methods , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Area Under Curve , Chemical and Drug Induced Liver Injury , Female , Humans , Male , Middle Aged , Odds Ratio , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/pharmacology , Retrospective Studies , Risk , Risk Factors , Young Adult
13.
J Org Chem ; 85(23): 15476-15487, 2020 Dec 04.
Article in English | MEDLINE | ID: mdl-33179920

ABSTRACT

We report the boron-catalyzed hydrophosphinylation of N-heteroaryl-substituted alkenes with secondary phosphine oxides that furnishes various phosphorus-containing N-heterocycles. This process proceeds under mild conditions and enables the introduction of a phosphorus atom into multisubstituted alkenylazaarenes. The available mechanistic data can be explained by a reaction pathway wherein the C-P bond is created by the reaction between the activated alkene (by coordination to a boron catalyst) and the phosphorus(III) nucleophile (in tautomeric equilibrium with phosphine oxide).

14.
Surg Endosc ; 33(10): 3334-3340, 2019 10.
Article in English | MEDLINE | ID: mdl-30604265

ABSTRACT

BACKGROUND: For therapeutic endoscopic retrograde cholangiopancreatography (ERCP), endoscopic sphincterotomy (ES) is necessary but it can lead to complications such as bleeding. Thus, we investigated the risk factors of post-ES bleeding in average risk patients. METHODS: We retrospectively reviewed the medical records of patients who had been treated for ERCP between April 2006 and March 2013. The length of the ES incision was defined as minimal (up to proximal hooding fold), medium (between minimal and full length), and full (up to superior margin of sphincter opening). Exclusion criteria were as follows: if performed precut sphincterotomy or balloon dilatation, patients having altered anatomy or anticoagulant medications. RESULTS: A total of 3620 patients underwent ERCP and 1121 patients who underwent biliary ES were enrolled. Post-ES bleeding occurred in 108 of 1121 patients (9.6%) and mostly minor bleeding (94 patients, 87%). Length of ES was the only risk factor for post-ES bleeding in multivariate analysis. Complete hemostasis was achieved by endoscopic modalities and no serious complication developed after hemostasis. CONCLUSIONS: In average risk patients, length of ES was independent risk factor for post-ES bleeding and endoscopic hemostasis was safe and effective.


Subject(s)
Bile Duct Diseases/surgery , Hemostasis, Endoscopic/methods , Postoperative Hemorrhage/etiology , Sphincterotomy, Endoscopic/adverse effects , Aged , Bile Duct Diseases/diagnosis , Cholangiopancreatography, Endoscopic Retrograde/methods , Female , Humans , Male , Postoperative Hemorrhage/diagnosis , Postoperative Hemorrhage/surgery , Retrospective Studies , Risk Factors
15.
J Am Chem Soc ; 140(1): 515-523, 2018 01 10.
Article in English | MEDLINE | ID: mdl-29215275

ABSTRACT

The synthesis of stable organic polyradicals is important for the development of magnetic materials. Herein we report the synthesis, isolation, and characterization of a series of X-shaped pyromellitimide (PI) oligomers (Xn-R, n = 2-4, R = Hex or Ph) linked together by single C-C bonds between their benzenoid cores. We hypothesize that these oligomers might form high-spin states in their reduced forms because of the nearly orthogonal conformations adopted by their PI units. 1H and 13C nuclear magnetic resonance (NMR) spectroscopies confirmed the isolation of the dimeric, trimeric, and tetrameric homologues. X-ray crystallography shows that X2-Ph crystallizes into a densely packed superstructure, despite the criss-crossed conformations adopted by the molecules. Electrochemical experiments, carried out on the oligomers Xn-Hex, reveal that the reductions of the PI units occur at multiple distinct potentials, highlighting the weak electronic coupling between the adjacent redox centers. Finally, the chemically generated radical anion and polyanion states, Xn-Hex•- and Xn-Hexn(•-), respectively, were probed extensively by UV-vis-NIR absorption, EPR, and electron nuclear double resonance (ENDOR) spectroscopies. The ENDOR spectra of the radical monoanions Xn-Hex•- reveal that the unpaired electron is largely localized on a single PI unit. Further reductions of Xn-Hex•- yield EPR signals (in frozen solutions) that can be assigned to spin-spin interactions in X2-Hex2(•-), X3-Hex3(•-), and X4-Hex4(•-). Taken together, these findings demonstrate that directly linking the benzene rings of PIs with a single C-C bond is a viable method for generating stabilized high-spin organic anionic polyradicals.

16.
J Am Chem Soc ; 140(36): 11402-11407, 2018 09 12.
Article in English | MEDLINE | ID: mdl-30092139

ABSTRACT

A class of metal-organic frameworks (MOFs)-namely CD-MOFs-obtained from natural products has been grown in an epitaxial fashion as films on the surfaces of glass substrates, which are modified with self-assembled monolayers (SAMs) of γ-cyclodextrin (γ-CD) molecules. The SAMs are created by host-guest complexation of γ-CD molecules with surface-functionalized pyrene units. The CD-MOF films have continuous polycrystalline morphology with a structurally out-of-plane ( c-axial) orientation, covering an area of several square millimeters, with a thickness of ∼2 µm. Furthermore, this versatile host-guest strategy has been applied successfully in the growth of CD-MOFs as the shell on the curved surface of microparticles as well as in the integration of CD-MOF films into electrochemical devices for sensing carbon dioxide. In striking contrast to the control devices prepared from CD-MOF crystalline powders, these CD-MOF film-based devices display an enhancement in proton conductance of up to 300-fold. In addition, the CD-MOF film-based device exhibits more rapid and highly reversible CO2-sensing cycles under ambient conditions, with a 50-fold decrease in conductivity upon exposure to CO2 for 3 s which is recovered within 10 s upon re-exposure to air.

17.
Toxicol Appl Pharmacol ; 296: 19-30, 2016 Apr 01.
Article in English | MEDLINE | ID: mdl-26879220

ABSTRACT

The glutathione precursor N-acetyl-L-cysteine (NAC) is currently being tested on Parkinson's patients for its neuroprotective properties. Our studies have shown that NAC can elicit protection in glutathione-independent manners in vitro. Thus, the goal of the present study was to establish an animal model of NAC-mediated protection in which to dissect the underlying mechanism. Mice were infused intrastriatally with the oxidative neurotoxicant 6-hydroxydopamine (6-OHDA; 4 µg) and administered NAC intraperitoneally (100mg/kg). NAC-treated animals exhibited higher levels of the dopaminergic terminal marker tyrosine hydroxylase (TH) in the striatum 10d after 6-OHDA. As TH expression is subject to stress-induced modulation, we infused the tracer FluoroGold into the striatum to retrogradely label nigrostriatal projection neurons. As expected, nigral FluoroGold staining and cell counts of FluoroGold(+) profiles were both more sensitive measures of nigrostriatal degeneration than measurements relying on TH alone. However, NAC failed to protect dopaminergic neurons 3 weeks following 6-OHDA, an effect verified by four measures: striatal TH levels, nigral TH levels, nigral TH(+) cell counts, and nigral FluoroGold levels. Some degree of mild toxicity of FluoroGold and NAC was evident, suggesting that caution must be exercised when relying on FluoroGold as a neuron-counting tool and when designing experiments with long-term delivery of NAC--such as clinical trials on patients with chronic disorders. Finally, the strengths and limitations of the tools used to define nigrostriatal degeneration are discussed.


Subject(s)
Acetylcysteine/therapeutic use , Corpus Striatum/pathology , Nerve Degeneration/pathology , Nerve Degeneration/prevention & control , Neuroprotective Agents/therapeutic use , Substantia Nigra/pathology , Acetylcysteine/pharmacology , Animals , Corpus Striatum/drug effects , Male , Mice , Nerve Degeneration/chemically induced , Neuroprotective Agents/pharmacology , Oxidopamine/toxicity , Substantia Nigra/drug effects
18.
Pancreatology ; 15(3): 305-7, 2015.
Article in English | MEDLINE | ID: mdl-25524485

ABSTRACT

There are two distinct subtypes of autoimmune pancreatitis (AIP): type 1 and type 2. Type 1 AIP is the pancreatic manifestation of systemic fibroinflammatory disease, which is named as IgG4-related disease. On the other hand, type 2 AIP is a pancreatic disorder that is not associated with IgG4. Type 1 and type 2 AIP have different clinical profiles and histologic findings. We present a 22-year-old man who has been diagnosed as type 1 AIP with histologically proven granulocytic epithelial lesion after surgical resection for pancreatic head mass. Since the patient had no pancreatic duct narrowing, elevation of serum IgG4, and other organ involvement, it was very difficult to diagnose preoperatively. This is a rare and interesting case in which histologic features of type 1 and type 2 AIP coexist.


Subject(s)
Autoimmune Diseases/pathology , Granulocytes/pathology , Pancreas/pathology , Pancreatitis/pathology , Autoimmune Diseases/immunology , Epithelium/pathology , Humans , Male , Pancreas/immunology , Pancreatitis/immunology , Young Adult
19.
J Am Chem Soc ; 136(13): 5090-6, 2014 Apr 02.
Article in English | MEDLINE | ID: mdl-24611651

ABSTRACT

Development of low cost, easy-to-use chemical sensor systems for low dose detection of γ radiation remains highly desired for medical radiation therapy and nuclear security monitoring. We report herein on a new fluorescence sensor molecule, 4,4'-di(1H-phenanthro[9,10-d]imidazol-2-yl)biphenyl (DPI-BP), which can be dissolved into halogenated solvents (e.g., CHCl3, CH2Cl2) to enable instant detection of γ radiation down to the 0.01 Gy level. The sensing mechanism is primarily based on radiation induced fluorescence quenching of DPI-BP. Pristine DPI-BP is strongly fluorescent in halogenated solvents. When exposed to γ radiation, the halogenated solvents decompose into various radicals, including hydrogen and chlorine, which then combine to produce hydrochloric acid (HCl). This strong acid interacts with the imidazole group of DPI-BP to convert it into a DPI-BP/HCl adduct. The DPI-BP/HCl adduct possesses a more planar configuration than DPI-BP, enhancing the π-π stacking and thus molecular aggregation. The strong molecular fluorescence of DPI-BP gets quenched upon aggregation, due to the π-π stacking interaction (forming forbidden low-energy excitonic transition). Interestingly the quenched fluorescence can be recovered simply by adding base (e.g., NaOH) into the solution to dissociate the DPI-BP/HCl adduct. Such sensing mechanism was supported by systematic investigations based on HCl titration and dynamic light scattering measurements. To further confirm that the aggregation caused fluorescence quenching, a half size analogue of DPI-BP, 2-phenyl-1H-phenanthro[9,10-d]imidazole (PI-Ph), was synthesized and investigated in comparison with the observations of DPI-BP. PI-Ph shares the same imidazole conjugation structure with DPI-BP and is expected to bind the same way with HCl. However, PI-Ph did not show fluorescence quenching upon binding with HCl likely due to the smaller π-conjugation structure, which can hardly enforce the π-π stacking assembly. Combining the low detection limit, fast and reversible fluorescence quenching response, and low cost of halogenated solvent composites, the sensor system presented may lead to the development of new, simple chemical dosimetry for low dose detection of γ radiation.


Subject(s)
Biphenyl Compounds/chemistry , Fluorescent Dyes/chemistry , Gamma Rays , Radiometry/methods , Spectrometry, Fluorescence/methods , Fluorescence , Halogenation , Limit of Detection , Solvents/chemistry
20.
Dig Dis Sci ; 59(5): 1055-62, 2014 May.
Article in English | MEDLINE | ID: mdl-24326631

ABSTRACT

BACKGROUND: Acute pancreatitis is an acute inflammatory process of the pancreas with variable involvement of other regional tissues or remote organ systems. Acute fluid collections and pseudocyst formation are the most frequent complications of acute pancreatitis. AIMS: The aims of this study were to evaluate the incidence, risk factors, and clinical course of pancreatic fluid collections and pseudocyst formation following acute pancreatitis. METHODS: A prospective multicenter study was conducted in five participating centers with 302 patients diagnosed with acute pancreatitis from January 2011 to July 2012. RESULTS: The incidence of pancreatic fluid collections and pseudocyst was 42.7 and 6.3 %, respectively. Patients with fluid collections were significantly younger, compared to those without fluid collections (51.5 ± 15.9 vs. 60.4 ± 16.5 years, P = 0.000). The proportion of alcoholic etiology (54.3 %) in patients with fluid collections was significantly higher compared to other etiologies (P = 0.000). C-reactive protein (CRP) (48 h) was significantly higher in patients with fluid collections, compared to patients without fluid collections (39.2 ± 77.4 vs. 15.1 ± 36.2 mg/dL, P = 0.016). LDH (48 h) was significantly higher in patients with pseudocyst formation, compared to patients with complete resolution (1,317.6 ± 706.4 vs. 478.7 ± 190.5 IU/L, P = 0.000). Pancreatic fluid collections showed spontaneous resolution in 69.8 % (90/129) and 84.2 % of the pseudocysts disappeared or decreased in size during follow up. CONCLUSIONS: Age, CRP (48 h), and alcohol etiology are risk factors for pancreatic fluid collections. LDH (48 h) appears to be a risk factor for pseudocyst formation. Most pseudocysts showed a decrease in size or spontaneous resolution with conservative management.


Subject(s)
Pancreatic Juice/metabolism , Pancreatic Pseudocyst/epidemiology , Pancreatitis/metabolism , Adult , Age Factors , Aged , Alcoholism/complications , C-Reactive Protein/metabolism , Female , Humans , Incidence , L-Lactate Dehydrogenase/metabolism , Male , Middle Aged , Pancreatic Pseudocyst/etiology , Pancreatitis/complications , Pancreatitis/etiology , Prospective Studies , Risk Factors
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