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1.
Cell Rep ; 43(7): 114426, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38959109

ABSTRACT

Understanding the role of B cells in tuberculosis (TB) is crucial for developing new TB vaccines. However, the changes in B cell immune landscapes during TB and their functional implications remain incompletely explored. Using high-dimensional flow cytometry to map the immune landscape in response to Mycobacterium tuberculosis (Mtb) infection, our results show an accumulation of marginal zone B (MZB) cells and other unconventional B cell subsets in the lungs and spleen, shaping an unconventional B cell landscape. These MZB cells exhibit activated and memory-like phenotypes, distinguishing their functional profiles from those of conventional B cells. Notably, functional studies show that MZB cells produce multiple cytokines and contribute to systemic protection against TB by shaping cytokine patterns and cell-mediated immunity. These changes in the immune landscape are reversible upon successful TB chemotherapy. Our study suggests that, beyond antibody production, targeting the regulatory function of B cells may be a valuable strategy for TB vaccine development.

2.
Integr Cancer Ther ; 22: 15347354231213613, 2023.
Article in English | MEDLINE | ID: mdl-38059303

ABSTRACT

BACKGROUND: Fucus vesiculosus-derived fucoidan, a multifunctional bioactive polysaccharide sourced from marine organisms, exhibits a wide range of therapeutic properties, including its anti-tumor effects. While previous research has reported on its anti-cancer potential, limited studies have explored its synergistic capabilities when combined with other natural bioactive ingredients. In this current study, we present the development of an integrative functional beverage, denoted as VMW-FC, which is composed of a fucoidan complex (FC) along with a blend of various herbal components, including vegetables (V), mulberries and fruits (M), and spelt wheat (W). OBJECTIVE: Colorectal cancer (CRC) remains a significant cause of mortality, particularly in metastatic cases. Therefore, the urgent need for novel alternative medicines that comprehensively inhibit CRC persists. In this investigation, we assess the impact of VMW-FC on CRC cell proliferation, cell cycle dynamics, metastasis, in vivo tumorigenesis, and potential side effects. METHODS: Cell growth was assessed using MTT and colony formation assays, while metastatic potential was evaluated through wound healing and transwell migration assays. The underlying signaling mechanisms were elucidated through qPCR and western blot analysis. In vivo tumor formation and potential side effects were evaluated using a subcutaneous tumor-bearing NOD/SCID mouse model. RESULTS: Our findings demonstrate that VMW-FC significantly impedes CRC proliferation and migration in a dose- and time-dependent manner. Furthermore, it induces sub-G1 cell cycle arrest and an increase in apoptotic cell populations, as confirmed through flow-cytometric analysis. Notably, VMW-FC also suppresses xenograft tumor growth in NOD/SCID mice without causing renal or hepatic toxicity. CONCLUSION: The integrative herbal concoction VMW-FC presents a promising approach for inhibiting CRC by slowing proliferation and migration, inducing cell cycle arrest and apoptosis, and suppressing markers associated with proliferation (Ki-67, PCNA, and CDKs) and epithelial-mesenchymal transition (EMT) (Vimentin, N-cadherin, and ß-catenin).


Subject(s)
Colorectal Neoplasms , Animals , Mice , Humans , Colorectal Neoplasms/metabolism , Cell Line, Tumor , Mice, Inbred NOD , Mice, SCID , Signal Transduction , Polysaccharides/pharmacology , Polysaccharides/therapeutic use , Cell Proliferation , Epithelial-Mesenchymal Transition , Cell Movement
3.
J Biomed Sci ; 30(1): 77, 2023 Sep 11.
Article in English | MEDLINE | ID: mdl-37691117

ABSTRACT

BACKGROUND: Bioactive materials have now raised considerable attention for the treatment of osteoarthritis (OA), such as knee OA, rheumatoid OA, and temporomandibular joint (TMJ) OA. TMJ-OA is a common disease associated with an imbalance of cartilage regeneration, tissue inflammation, and disability in mouth movement. Recently, biological materials or molecules have been developed for TMJ-OA therapy; however, ideal treatment is still lacking. In this study, we used the combination of a human platelet rich plasma with hyaluronic acid (hPRP/HA) for TMJ-OA therapy to perform a clinical trial in dish to humans. METHOD: Herein, hPRP was prepared, and the hPRP/HA combined concentration was optimized by MTT assay. For the clinical trial in dish, pro-inflammatory-induced in-vitro and in-vivo mimic 3D TMJ-OA models were created, and proliferation, gene expression, alcian blue staining, and IHC were used to evaluate chondrocyte regeneration. For the animal studies, complete Freund's adjuvant (CFA) was used to induce the TMJ-OA rat model, and condyle and disc regeneration were investigated through MRI. For the clinical trial in humans, 12 patients with TMJ-OA who had disc displacement and pain were enrolled. The disc displacement and pain at baseline and six months were measured by MRI, and clinical assessment, respectively. RESULTS: Combined hPRP/HA treatment ameliorated the proinflammatory-induced TMJ-OA model and promoted chondrocyte proliferation by activating SOX9, collagen type I/II, and aggrecan. TMJ-OA pathology-related inflammatory factors were efficiently downregulated with hPRP/HA treatment. Moreover, condylar cartilage was regenerated by hPRP/HA treatment in a proinflammatory-induced 3D neocartilage TMJ-OA-like model. During the animal studies, hPRP/HA treatment strongly repaired the condyle and disc in a CFA-induced TMJ-OA rat model. Furthermore, we performed a clinical trial in humans, and the MRI data demonstrated that after 6 months of treatment, hPRP/HA regenerated the condylar cartilage, reduced disc displacement, alleviated pain, and increased the maximum mouth opening (MMO). Overall, clinical trials in dish to human results revealed that hPRP/HA promoted cartilage regeneration, inhibited inflammation, reduced pain, and increased joint function in TMJ-OA. CONCLUSION: Conclusively, this study highlighted the therapeutic potential of the hPRP and HA combination for TMJ-OA therapy, with detailed evidence from bench to bedside. Trial registration Taipei Medical University Hospital (TMU-JIRB No. N201711041). Registered 24 November 2017. https://tmujcrc.tmu.edu.tw/inquiry_general.php .


Subject(s)
Hyaluronic Acid , Osteoarthritis, Knee , Humans , Animals , Rats , Hyaluronic Acid/pharmacology , Hyaluronic Acid/therapeutic use , Pain , Inflammation , Biocompatible Materials
4.
mBio ; 14(2): e0059823, 2023 04 25.
Article in English | MEDLINE | ID: mdl-37017524

ABSTRACT

Caseous necrosis is a hallmark of tuberculosis (TB) pathology and creates a niche for drug-tolerant persisters within the host. Cavitary TB and high bacterial burden in caseum require longer treatment duration. An in vitro model that recapitulates the major features of Mycobacterium tuberculosis (Mtb) in caseum would accelerate the identification of compounds with treatment-shortening potential. We have developed a caseum surrogate model consisting of lysed and denatured foamy macrophages. Upon inoculation of Mtb from replicating cultures, the pathogen adapts to the lipid-rich matrix and gradually adopts a nonreplicating state. We determined that the lipid composition of ex vivo caseum and the surrogate matrix are similar. We also observed that Mtb in caseum surrogate accumulates intracellular lipophilic inclusions (ILI), a distinctive characteristic of quiescent and drug-tolerant Mtb. Expression profiling of a representative gene subset revealed common signatures between the models. Comparison of Mtb drug susceptibility in caseum and caseum surrogate revealed that both populations are similarly tolerant to a panel of TB drugs. By screening drug candidates in the surrogate model, we determined that the bedaquiline analogs TBAJ876 and TBAJ587, currently in clinical development, exhibit superior bactericidal against caseum-resident Mtb, both alone and as substitutions for bedaquiline in the bedaquiline-pretomanid-linezolid regimen approved for the treatment of multidrug-resistant TB. In summary, we have developed a physiologically relevant nonreplicating persistence model that reflects the distinct metabolic and drug-tolerant state of Mtb in caseum. IMPORTANCE M. tuberculosis (Mtb) within the caseous core of necrotic granulomas and cavities is extremely drug tolerant and presents a significant hurdle to treatment success and relapse prevention. Many in vitro models of nonreplicating persistence have been developed to characterize the physiologic and metabolic adaptations of Mtb and identify compounds active against this treatment-recalcitrant population. However, there is little consensus on their relevance to in vivo infection. Using lipid-laden macrophage lysates, we have designed and validated a surrogate matrix that closely mimics caseum and in which Mtb develops a phenotype similar to that of nonreplicating bacilli in vivo. The assay is well suited to screen for bactericidal compounds against caseum-resident Mtb in a medium-throughput format, allowing for reduced reliance on resource intensive animal models that present large necrotic lesions and cavities. Importantly, this approach will aid the identification of vulnerable targets in caseum Mtb and can accelerate the development of novel TB drugs with treatment-shortening potential.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Tuberculosis , Animals , Mycobacterium tuberculosis/genetics , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , Tuberculosis/drug therapy , Tuberculosis/microbiology , Lipids
5.
Molecules ; 28(4)2023 Feb 08.
Article in English | MEDLINE | ID: mdl-36838626

ABSTRACT

The objective of this study was to develop a simultaneous analysis method of furan and its 10 derivatives in different food commodities. The results indicated that furan and its 10 derivatives could be separated within 9.5 min by using a HP-5MS column and gas chromatography-tandem mass spectrometry (GC-MS/MS) with multiple reaction monitoring mode for detection. Furthermore, this method could resolve several furan isomers, such as 2-methyl furan and 3-methyl furan, as well as 2,3-dimethyl furan and 2,5-dimethyl furan. The most optimal extraction conditions were: 5 g of the fruit or juice sample mixed with 5 mL of the saturated NaCl solution, separately, or 1 g of the canned oily fish sample mixed with 9 mL of the saturated NaCl solution, followed by the equilibration of each sample at 35 °C for 15 min, using a carboxen-polydimethylsiloxane SPME arrow to adsorb the analytes for 15 min at 35 °C for subsequent analysis by GC-MS/MS. For method validation of all the analytes in the different food matrices, the recovery was 76-117% and the limit of the quantitation was 0.003-0.675 ng/g, while the relative standard deviation (RSD%) of the intra-day variability range from 1-16%, and that of the inter-day variability was from 4-20%. The method validation data further demonstrated that a reliable method was established for the analysis of furan and its 10 derivatives in commercial foods.


Subject(s)
Sodium Chloride , Tandem Mass Spectrometry , Animals , Gas Chromatography-Mass Spectrometry/methods , Solid Phase Microextraction/methods , Solid Phase Extraction , Furans/chemistry , Fruit/chemistry
6.
Sci Rep ; 12(1): 18670, 2022 11 04.
Article in English | MEDLINE | ID: mdl-36333461

ABSTRACT

This study aims at identifying characteristics, risk factors and mortality of community-acquired (CAP) and health-care-associated pneumonia (HCAP) by Staphylococcus aureus (S. aureus). We retrieved adults with S. aureus CAP or HCAP diagnosed by blood or pleural effusion culture in 2.6 years, and compared with those of Streptococcus pneumoniae (S. pneumoniae) CAP or HCAP diagnosed by blood or respiratory culture, or urine antigen. We found 18 patients with CAP and 9 HCAP due to S. aureus (female 33%, 66.6 ± 12.4 years-old), and 48 patients with CAP and 15 HCAP due to S pneumoniae (female 41%, 69.5 ± 17.5 years). Diabetes mellitus (52% vs. 24%, p = 0.019), hemodialysis (11% vs. 0%, p = 0.046), skin lesions (44% vs. 0%, p < 0.001), cavitary nodules (37% vs. 1.6%, p < 0.001) and pleural effusions (48% vs. 18%, p = 0.007) were more common in staphylococcal than pneumococcal group. Three patients with staphylococcal pneumonia had acute myocardial infarction. Pneumonia severity index (139 ± 52 vs. 109 ± 43, p = 0.005) and 30-day mortality (41% vs. 9.5%, p = 0.001) were higher in staphylococcal group. Multivariate analysis showed underlying disease (especially cancer and cirrhosis), risk class 4/5, altered mentality, shock and bilateral pneumonia were risk factors for 30-day mortality.


Subject(s)
Community-Acquired Infections , Cross Infection , Healthcare-Associated Pneumonia , Pneumonia, Staphylococcal , Pneumonia , Adult , Humans , Female , Middle Aged , Aged , Staphylococcus aureus , Community-Acquired Infections/diagnosis , Pneumonia, Staphylococcal/epidemiology , Pneumonia, Staphylococcal/drug therapy , Cross Infection/drug therapy , Retrospective Studies , Pneumonia/drug therapy , Healthcare-Associated Pneumonia/drug therapy , Streptococcus pneumoniae , Risk Factors , Anti-Bacterial Agents/therapeutic use
7.
J Food Drug Anal ; 30(4): 614-629, 2022 11 23.
Article in English | MEDLINE | ID: mdl-36753362

ABSTRACT

This study explored the effects of sterilization conditions on the formation of furan and its 10 derivatives in canned foods with a sterilizing value (F0) at 4. The contents of furans were determined by SPME arrow-GC-MS/MS, along with the furan precursors analyzed for elucidating the possible mechanism of furan formation. Results revealed that the total furan contents rose substantially in canned meat paste, tomato mackerel, chicken puree, tomato paste, pineapple slice, pineapple juice and carrot juice following sterilization. However, the total furan content did not change significantly ( p > 0.05) in canned oily mackerel, but decreased significantly ( p < 0.05) in canned apple puree after sterilization. With the exception of apple puree and pineapple slice, all the other canned foods showed a higher total furan content under low-temperature-long-time condition than that under high-temperature-short-time condition. Following heating, only the furan level showed a large increase in chicken puree, meat paste and tomato mackerel, whereas in canned fruit- and vegetable-based foods, the contents of furan and furfural showed a pronounced increase. The levels of alkylated furans were higher in sterilized samples containing high level of amino acid, while that of oxygenated furans were higher in sterilized samples containing high level of reducing sugar.


Subject(s)
Furans , Tandem Mass Spectrometry , Furans/chemistry , Food, Preserved , Sterilization
8.
Life (Basel) ; 11(10)2021 Oct 07.
Article in English | MEDLINE | ID: mdl-34685425

ABSTRACT

Complications of diabetes mellitus (DM) range from acute to chronic conditions, leading to multiorgan disorders such as nephropathy, retinopathy, and neuropathy. However, little is known about the influence of DM on intervertebral disc degeneration (IVDD). Moreover, traditional surgical outcomes in DM patients have been found poor, and to date, no definitive alternative treatment exists for DM-induced IVDD. Recently, among various novel approaches in regenerative medicine, the concentrated platelet-derived biomaterials (PDB), which is comprised of transforming growth factor-ß1 (TGF-ß1), platelet-derived growth factor (PDGF), etc., have been reported as safe, biocompatible, and efficacious alternatives for various disorders. Therefore, we initially investigated the correlations between DM and IVDD, through establishing in vitro and in vivo DM models, and further evaluated the therapeutic effects of PDB in this comorbid pathology. In vitro model was established by culturing immortalized human nucleus pulposus cells (ihNPs) in high-glucose medium, whereas in vivo DM model was developed by administering streptozotocin, nicotinamide and high-fat diet to the mice. Our results revealed that DM deteriorates both ihNPs and IVD tissues, by elevating reactive oxygen species (ROS)-induced oxidative stress, inhibiting chondrogenic markers and disc height. Contrarily, PDB ameliorated IVDD by restoring cellular growth, chondrogenic markers and disc height, possibly through suppressing ROS levels. These data imply that PDB may serve as a potential chondroprotective and chondroregenerative candidate for DM-induced IVDD.

9.
Acta Neurol Taiwan ; 29(3): 95-98, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32996118

ABSTRACT

PURPOSE: Spinal infarction is a rare condition and usually presents with a sudden or acute course. A prolonged course is rare and may mimic the presentation of inflammatory myelitis. Here we present a case of atypical spinal cord infarction with a stuttering course for six days.. CASE REPORT: A 47-year-old male presented initially with symptoms of sudden onset, limb pain. Sudden chest pain radiating to the back, occurred three days later. Sudden urinary retention and quadriparesis were presented after another three days. The diagnosis of spinal cord infarction was made through diffusion restriction in spinal magnetic resonance imaging. CONCLUSION: A prolonged course of spinal cord infarction is relatively uncommon but a stepwise and stuttering course may provide clues. Diffusion restriction in magnetic resonance imaging also may be helpful. The diagnosis of spinal cord infarction should always be kept in mind.


Subject(s)
Spinal Cord Diseases , Stuttering , Humans , Infarction , Magnetic Resonance Imaging , Male , Middle Aged , Pain , Spinal Cord
10.
J Affect Disord ; 253: 171-175, 2019 06 15.
Article in English | MEDLINE | ID: mdl-31035218

ABSTRACT

BACKGROUND: Cardiometabolic diseases are suggested to be associated with bipolar disorder. However, the risk of metabolic disorders in unaffected siblings of patients with bipolar disorder remains unclear. METHODS: From the Taiwan National Health Insurance Research Database, 7,225 unaffected siblings of bipolar probands and 28,900 age-/sex-/income-/residence-matched control individuals were included and followed until the end of 2011. Individuals who developed metabolic disorders during the follow-up period were identified. RESULTS: The unaffected siblings of bipolar probands had a higher prevalence of dyslipidemia (5.4% vs. 4.5%, p = 0.001), younger age at diagnosis of type 2 diabetes mellitus (34.81 vs. 37.22, p = 0.024), and higher prevalence of any stroke (1.5% vs. 1.1%, p = 0.007) than the controls. Moreover, only male siblings of bipolar probands had an increased risk of dyslipidemia (odds ratio [OR]: 1.28, 95% confidence interval [CI]: 1.10-1.48) and higher rates of any stroke (OR: 1.38, 95% CI: 1.02-1.85) and ischemic stroke (OR: 2.43, 95% CI: 1.60-3.70) during the follow-up compared with the controls. DISCUSSION: Unaffected siblings of bipolar patients, particularly brothers, had a higher prevalence of dyslipidemia and ischemic stroke compared with the controls. The result suggests the familial association between cardiometabolic diseases and bipolar disorder. Further research may be necessary to identify this shared etiology between the disorders.


Subject(s)
Bipolar Disorder/genetics , Diabetes Mellitus, Type 2/epidemiology , Dyslipidemias/epidemiology , Genetic Predisposition to Disease/epidemiology , Stroke/epidemiology , Adult , Databases, Factual , Diabetes Mellitus, Type 2/genetics , Dyslipidemias/genetics , Female , Humans , Male , Middle Aged , Odds Ratio , Pedigree , Prevalence , Risk Factors , Siblings , Stroke/genetics , Taiwan/epidemiology
11.
Oncoimmunology ; 7(9): e1477459, 2018.
Article in English | MEDLINE | ID: mdl-30228946

ABSTRACT

Immunotherapies have shown promising results in certain cancer patients. For hepatocellular carcinoma (HCC), the multiplicity of an immunotolerant microenvironment within both the tumor, and the liver per se may limit the efficacy of cancer immunotherapies. Since radiation induces immunogenic cell death and inflammatory reactions within the tumor microenvironment, we hypothesized that a combination therapy of radiation and lasting local immunostimulating agents, achieved by intratumoral injection of an adenoviral vector encoding interleukin 12, may reverse the immunotolerant microenvironment within a well-established orthotopic HCC toward a state favorable for inducing antitumor immunities. Our data showed that radiation and IL-12 combination therapy (RT/IL-12) led to dramatic tumor regression in animals bearing large subcutaneous or orthotopic HCC, induced systemic effect against distant tumor, and significantly prolonged survival. Radiation monotherapy induced tumor regression at early times but afterwards most tumors regained exponential growth, while IL-12 monotherapy only delayed tumor growth. Mechanistic studies revealed that RT/IL-12 increased expression of MHC class II and co-stimulatory molecules CD40 and CD86 on tumor-infiltrating dendritic cells, suggesting an improvement of their antigen presentation activity. RT/IL-12 also significantly reduced accumulation of tumor-infiltrating myeloid-derived suppressor cells (MDSCs) and impaired their suppressive functions by reducing production of reactive oxygen species. Accordingly, tumor-infiltrating CD8+ T cells and NK cells were significantly activated toward the antitumor phenotype, as revealed by increased expression of CD107a and TNF-α. Together, our data showed that RT/IL-12 treatment could reset the intratumoral immunotolerant state and stimulate activation of antitumor cellular immunity that is capable of eliminating large established HCC tumors.

12.
Int Psychogeriatr ; 30(8): 1189-1197, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29223190

ABSTRACT

ABSTRACTBackground:Dementia screening is a public health priority in Taiwan, where the prevalence of dementia is increasing because of an aging population. However, the reasons affect community-dwelling people to accept a referral to memory specialist clinic after dementia screening was still unclear. To investigate the feasibility, acceptability, sensitivity, and specificity of the ascertain dementia 8-item informant questionnaire (AD8) to screen for patients with cognitive impairments in Taiwan's primary healthcare system. METHODS: Researchers invited community-dwelling people whose age was above 50-year-old to attend the Memory Screening Project. AD8 was used to perform the informant interview with adult patients who were attending the Memory Screening Project in Taiwan. Individuals who scored ≥2 on the AD8 was suggested to accept referral for further cognitive performance evaluation tests, which included three validated dementia tests, i.e. the Mini-Mental Screening Examination (MMSE), the Cognitive Abilities Screening Instrument (CASI), and the Clinical Dementia Rating (CDR). RESULTS: Of the 102 participants who scored ≥2 on the AD8, only 25.5% attended the referral appointment. In participants who had achieved six or more years of education, AD8 scores were not significantly different between groups and could not differentiate between the non-dementia and patients with dementia in the receiver-operator characteristics curve analysis. In contrast, in those participants who had received less than six years of education, the AD8 scores significantly differentiated between non-dementia and patients with dementia (p = 0.03). CONCLUSIONS: There was a low rate of attendance at a specialist memory clinic following referral after the AD8 interview. Higher levels of education facilitated individuals to make a decision to accept the recommended referral appointment, while the AD8 showed a higher rate of differentiation between individuals who had received an education of less than six years.


Subject(s)
Cognitive Dysfunction/diagnosis , Dementia/diagnosis , Educational Status , Mass Screening/methods , Adult , Aged , Aged, 80 and over , Ambulatory Care Facilities , Cognitive Dysfunction/epidemiology , Dementia/epidemiology , Female , Humans , Male , Mental Status and Dementia Tests , Middle Aged , Primary Health Care , ROC Curve , Retrospective Studies , Sensitivity and Specificity , Sex Factors , Surveys and Questionnaires , Taiwan/epidemiology
13.
Psychogeriatrics ; 17(6): 364-370, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28261945

ABSTRACT

AIM: The relationship between declining performance, as measured by changes in reaction time, and declining cognitive function has not been critically studied. The aim of the present study was to investigate the association between reaction time during a task and cognitive ability in elderly Taiwanese individuals. METHODS: Patients aged 65 years or older with mild cognitive impairment (MCI) (n = 33) and Alzheimer's disease (n = 26) were recruited from the neurology clinic of a regional hospital in southern Taiwan. In addition, 28 healthy controls aged 65 years or older were recruited from the community. The cognitive performance of the study participants was assessed using the Cognitive Abilities Screening Instrument (CASI). A computer-administered simple reaction time (SRT) task and a flanker reaction time (FRT) task were administered to assess participants' cognitive function. A non-parametric Kruskal-Wallis test was performed to compare CASI scores, SRT, and FRT among the three groups. anova was also used to compare CASI scores, inverse-transformed SRT, and inverse-transformed FRT among the three groups, with adjustment for age and years of education. Additionally, Pearson's partial correlation coefficients were used to assess the association of CASI scores with inverse-transformed SRT, and inverse-transformed FRT within each of the three groups. RESULTS: Significant differences in CASI scores, SRT, and FRT were found between the Alzheimer's disease group and the other two groups, either with or without adjustment for age or education. The reaction time of patients with Alzheimer's disease was significantly slower than the other two groups. Moreover, significant correlation between CASI and FRT was found in patients with MCI. CONCLUSION: Altered performance in a speed task was observed in patients with MCI. The FRT task should further be explored for its role as a marker for cognitive decline in elderly individuals, particularly in those with MCI.


Subject(s)
Alzheimer Disease/diagnosis , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/psychology , Psychomotor Performance , Reaction Time/physiology , Aged , Aged, 80 and over , Case-Control Studies , Cognitive Dysfunction/complications , Humans , Motor Skills , Neuropsychological Tests , Taiwan , Task Performance and Analysis
14.
J Vet Diagn Invest ; 28(5): 599-603, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27493139

ABSTRACT

A 5-year-old male captive corn snake (Pantherophis guttatus) with caudal coelomic swelling was admitted for surgical treatment. Laparotomy revealed a 5 × 4 × 2.5 cm, firm, expansile, irregularly shaped mass arising from the middle portion of the right kidney with a mild lobulated pattern and mottled white-to-tan. Microscopically, the mass was composed of numerous bizarre angulated tubules of polygonal neoplastic cells separated by a scirrhous stroma with remarkable heterophilic infiltrates. The neoplastic cells were nonciliated and mucin secreting, with abundant brightly eosinophilic cytoplasm. There were marked cellular and nuclear atypia, frequent cell individualization, and stromal invasion, indicative of malignant behavior, which was confirmed by metastasis to the left kidney 1.5 months postoperatively. Both neoplastic epithelial cells and mesenchymal cells contributing to the scirrhous stroma had variable immunopositivity for pan-cytokeratin. The neoplasm was considered a renal adenocarcinoma resembling human collecting duct carcinoma.


Subject(s)
Carcinoma, Renal Cell/veterinary , Kidney Neoplasms/veterinary , Snakes , Animals , Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/pathology , Diagnosis, Differential , Kidney Neoplasms/diagnosis , Kidney Neoplasms/pathology , Male
15.
J Org Chem ; 80(10): 5189-95, 2015 May 15.
Article in English | MEDLINE | ID: mdl-25909506

ABSTRACT

The ß-selective phenylation of benzyl and boronate protected 1,6-anhydroglucose and the direct phenylation of unprotected 1,6-anhydroglucose (10), pretreated with i-Bu2AlH, i-Bu3Al, Et3Al, Me3Al, or n-octyl3Al, with triphenylalane or aryl(chloro)alanes is reported. The utility of the unprotected version of the method is demonstrated by the synthesis of the SGLT2 inhibitor, canagliflozin (1a), from commercially available 10 in one C-C bond-forming step. This approach circumvents the need for conventional protecting groups, and therefore no formal protection and deprotection steps are required.


Subject(s)
Canagliflozin/chemical synthesis , Glucose/analogs & derivatives , Glucose/chemistry , Organometallic Compounds/chemistry , Canagliflozin/chemistry , Catalysis , Hypoglycemic Agents , Molecular Structure
16.
Neurologist ; 19(2): 46-8, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25607332

ABSTRACT

BACKGROUND: Baló's concentric sclerosis (BCS), a rare variant of multiple sclerosis (MS), as the initial presentation of antiphospholipid syndrome (APS) is unusual. The pathogenic role of antiphospholipid antibodies in the development of MS remains unknown. Anticoagulant therapy might be used in patients with MS and APS for prevention against the relapse of MS. CASE REPORT: We present a 27-year-old man diagnosed as BCS with APS. Initially, after corticosteroid therapy, he exhibited a complete recovery. During follow-up, his Baló-like lesion dissolved over time but transformed into other asymptomatic MS-like lesions. He also had persistently elevated anticardiolipin IgG levels. The patient was, therefore, on a combined therapy of interferon ß-1b and an anticoagulant agent. No new brain lesions were found on 2 occasional head magnetic resonance imaging studies at 1 year follow-up. CONCLUSIONS: To prevent further MS relapse and thrombotic complications of APS, a combined therapy of interferon ß-1b and an anticoagulant agent can be an important strategy in treating patients with both BCS and APS.


Subject(s)
Adjuvants, Immunologic/therapeutic use , Anesthetics, Local/therapeutic use , Antiphospholipid Syndrome/drug therapy , Diffuse Cerebral Sclerosis of Schilder/drug therapy , Ethyl Chloride/therapeutic use , Interferon-beta/therapeutic use , Adult , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/diagnosis , Brain/pathology , Diffuse Cerebral Sclerosis of Schilder/complications , Diffuse Cerebral Sclerosis of Schilder/diagnosis , Humans , Interferon beta-1b , Magnetic Resonance Imaging , Male
17.
Kidney Int ; 86(6): 1174-86, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24918157

ABSTRACT

Chronic kidney disease (CKD) is an emerging worldwide public health problem. Inflammatory cell infiltration and activation during the early stages in injured kidneys is a common pathologic feature of CKD. Here, we determined whether an important inflammatory regulator, triggering receptor expressed on myeloid cells (TREM)-1, is upregulated in renal tissues collected from mouse ureteral obstruction-induced nephritis. TREM-1 is crucial for modulating macrophage polarization, and has a pivotal role in mediating tubular injury and interstitial collagen deposition in obstructive nephritis. Lysates from nephritic kidneys triggered a TREM-1-dependent M1 polarization ex vivo, consistent with the observation that granulocyte-macrophage colony-stimulating factor (GM-CSF)-derived M1 macrophages express higher levels of TREM-1 in comparison with M-CSF-derived cells. Moreover, agonistic TREM-1 cross-link significantly strengthens the inductions of iNOS and GM-CSF in M1 cells. These observations are validated by a strong clinical correlation between infiltrating TREM-1-expressing/iNOS-positive macrophages and renal injury in human obstructive nephropathy. Thus, TREM-1 may be a potential diagnostic and therapeutic target in human kidney disease.


Subject(s)
Cell Polarity , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Macrophages/physiology , Membrane Glycoproteins/metabolism , Nephritis/metabolism , Nitric Oxide Synthase Type II/metabolism , Receptors, Immunologic/metabolism , Ureteral Obstruction/metabolism , Adult , Aged , Aged, 80 and over , Animals , Cell Differentiation , Cells, Cultured , Disease Models, Animal , Female , Humans , Male , Membrane Glycoproteins/genetics , Mice , Mice, Knockout , Middle Aged , Nephritis/etiology , Nephritis/pathology , RNA, Messenger/metabolism , Receptors, Immunologic/genetics , Triggering Receptor Expressed on Myeloid Cells-1 , Up-Regulation , Ureteral Obstruction/complications , Ureteral Obstruction/pathology
18.
Hu Li Za Zhi ; 60(4): 65-75, 2013 Aug.
Article in Chinese | MEDLINE | ID: mdl-23922092

ABSTRACT

BACKGROUND: Although high-technology wound dressings are widely used in clinical care worldwide, no evidence or discussions have been published regarding the efficacy of these dressings in preventing pressure ulcers. PURPOSE: This study presents a repositioning of routine management combined with hydrocolloid dressing or foam dressing for pressure ulcer prevention. METHODS: We used a quasi-experimental design and recruited a convenience sample of 90 from a surgical intensive care unit (SICU) at a medical center in Hualien County, Taiwan. Participants were allocated randomly to one of three groups: repositioning of routine management, hydrocolloid dressing, and foam dressing. Study instruments included a pressure ulcer risk table (Braden scale) and the pressure ulcer classification system of the European Pressure Ulcer Advisory Panel. An independent sample t-test, ANOVA, and Mann-Whitney U test were used to verify research hypotheses. RESULTS: The repositioning of routine management group had the highest pressure ulcer incidence rate, followed by the hydrocolloid-dressing group. The foam-dressing group recorded no pressure ulcers. Pressure ulcer occurrence grades were primarily level 1 and 2. There was no significance difference in pressure ulcer occurrence time between the repositioning of routine-management group and the hydrocolloid-dressing group. Finally, there were significant differences (p < .05) among gender, hypertension history, and BMI regardless of pressure ulcer incidences. CONCLUSIONS: It is recommended that patients in high-risk groups in clinical settings adopt strategies including repositioning and regular visual skin examinations. Also, hydrocolloid or foam dressings may be used as appropriate to prevent sacral pressure ulcers.


Subject(s)
Bandages, Hydrocolloid , Occlusive Dressings , Pressure Ulcer/prevention & control , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Pressure Ulcer/epidemiology
19.
Am J Emerg Med ; 31(5): 888.e1-3, 2013 May.
Article in English | MEDLINE | ID: mdl-23602751

ABSTRACT

Cerebral venous sinus thrombosis is a rare neurologic manifestation of antiphospholipid syndrome. We report a case of a 49-year-old woman who presented to the emergency department with recurrent episodes of transient clumsiness of the left upper extremity. The results of unenhanced brain computed tomography and electroencephalography were unremarkable. Serial neuroimages revealed superior sagittal sinus thrombosis. Thrombophilia screen disclosed positive lupus anticoagulant. In this case report, we aim to emphasize the significance of recognizing an unusual presentation of antiphospholipid syndrome.


Subject(s)
Antiphospholipid Syndrome/diagnosis , Sinus Thrombosis, Intracranial/etiology , Antiphospholipid Syndrome/complications , Female , Humans , Middle Aged , Muscle Weakness/etiology , Sinus Thrombosis, Intracranial/diagnosis
20.
J Formos Med Assoc ; 108(6): 518-22, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19515634

ABSTRACT

A 26-year-old man with a 3-year history of heroin vapor inhalation developed spongiform leukoencephalopathy. T2-weighted magnetic resonance imaging showed characteristic high signals over subcortical white matter, including bilateral frontoparietal lobes, posterior limbs of internal capsules, splenium, occipital lobes, cerebellum and brainstem. Signal intensity of diffusion-weighted imaging was high, and apparent diffusion coefficient in corresponding areas was increased. Pathologic features of heroin induced spongiform leukoencephalopathy were unique, characterized by demyelination and vacuolar formation. 99m-Technetium-ECD SPECT and F18 FDG PET demonstrated decreased radiotracer uptake in the corresponding areas. 99m-Technetium-TRODAT SPECT showed no definite decreased uptake of radiotracer at basal ganglia, which suggests that the dopamine neurons were not affected.


Subject(s)
Brain Diseases/chemically induced , Heroin/poisoning , Narcotics/poisoning , Administration, Inhalation , Adult , Brain/diagnostic imaging , Brain/pathology , Heroin/administration & dosage , Humans , Male , Tomography, Emission-Computed, Single-Photon , Volatilization
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