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1.
Ann Oncol ; 29(suppl_1): i3-i9, 2018 01 01.
Article in English | MEDLINE | ID: mdl-29462253

ABSTRACT

Front-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) therapy is the standard of care for lung cancer patients with sensitising EGFR mutations (exon 19 deletion or L858R mutation). Several phase III studies have demonstrated the superiority of gefitinib, erlotinib (first generation of TKIs) or afatinib (second generation) to chemotherapy in progression-free survival and response rates. Drug-related toxicities, such as diarrhoea, acneiform skin rash, mucositis, and paronychia, are frequently encountered in patients who receive EGFR TKIs. Other rare side-effects, such as hepatic impairment and interstitial lung disease, should be identified early and managed carefully. Patients with uncommon EGFR mutations, such as G719X, S768I, and L861Q, may require special selection of EGFR TKIs. The combination of erlotinib plus bevacizumab has been accepted in certain parts of the world as an alternative front-line treatment. This review article summarizes the studies leading to the establishment of EGFR TKIs in EGFR-mutant lung cancer patients. The side-effect profiles of the current EGFR TKIs in these large trials are listed, and the management of uncommon EGFR mutations is discussed. Finally, the potential role of combination front-line treatment is discussed.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Protein Kinase Inhibitors/administration & dosage , Acneiform Eruptions/chemically induced , Acneiform Eruptions/epidemiology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bevacizumab/administration & dosage , Bevacizumab/adverse effects , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/mortality , Chemical and Drug Induced Liver Injury/epidemiology , Chemical and Drug Induced Liver Injury/etiology , Diarrhea/chemically induced , Diarrhea/epidemiology , Drug Resistance, Neoplasm/genetics , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , Erlotinib Hydrochloride/administration & dosage , Erlotinib Hydrochloride/adverse effects , Exons/genetics , Humans , Lung Diseases, Interstitial/chemically induced , Lung Diseases, Interstitial/epidemiology , Lung Neoplasms/genetics , Lung Neoplasms/mortality , Molecular Targeted Therapy/adverse effects , Molecular Targeted Therapy/methods , Mucositis/chemically induced , Mucositis/epidemiology , Paronychia/chemically induced , Paronychia/epidemiology , Patient Selection , Progression-Free Survival , Protein Kinase Inhibitors/adverse effects , Randomized Controlled Trials as Topic
2.
Br J Dermatol ; 178(6): 1246-1256, 2018 06.
Article in English | MEDLINE | ID: mdl-28714085

ABSTRACT

BACKGROUND: Humans have 4 million exocrine sweat glands, which can be classified into two types: eccrine and apocrine glands. Sweat secretion, a constitutive feature, is directly involved in thermoregulation and metabolism, and is regulated by both the central nervous system (CNS) and autonomic nervous system (ANS). OBJECTIVES: To explore how sweat secretion is controlled by both the CNS and the ANS and the mechanisms behind the neural control of sweat secretion. METHODS: We conducted a literature search on PubMed for reports in English from 1 January 1950 to 31 December 2016. RESULTS AND CONCLUSIONS: Acetylcholine acts as a potent stimulator for sweat secretion, which is released by sympathetic nerves. ß-adrenoceptors are found in adipocytes as well as apocrine glands, and these receptors may mediate lipid secretion from apocrine glands for sweat secretion. The activation of ß-adrenoceptors could increase sweat secretion through opening of Ca2+ channels to elevate intracellular Ca2+ concentration. Ca2+ and cyclic adenosine monophosphate play a part in the secretion of lipids and proteins from apocrine glands for sweat secretion. The translocation of aquaporin 5 plays an important role in sweat secretion from eccrine glands. Dysfunction of the ANS, especially the sympathetic nervous system, may cause sweating disorders, such as hypohidrosis and hyperhidrosis.


Subject(s)
Apocrine Glands/metabolism , Autonomic Nervous System/physiology , Central Nervous System/physiology , Eccrine Glands/metabolism , Sweat/metabolism , Acetylcholine/physiology , Apocrine Glands/innervation , Body Temperature Regulation/physiology , Calcium Channels/physiology , Cyclic AMP/physiology , Eccrine Glands/innervation , Humans , Limbic System/physiology , Norepinephrine/physiology , Receptors, Adrenergic, beta/physiology , Receptors, G-Protein-Coupled/physiology , Secretory Pathway/physiology , Sweat Gland Diseases/physiopathology
3.
Public Health ; 161: 127-137, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29195682

ABSTRACT

OBJECTIVES: The frequency and intensity of extreme heat events are increasing in New York State (NYS) and have been linked with increased heat-related morbidity and mortality. But these effects are not uniform across the state and can vary across large regions due to regional sociodemographic and environmental factors which impact an individual's response or adaptive capacity to heat and in turn contribute to vulnerability among certain populations. We developed a heat vulnerability index (HVI) to identify heat-vulnerable populations and regions in NYS. STUDY DESIGN: Census tract level environmental and sociodemographic heat-vulnerability variables were used to develop the HVI to identify heat-vulnerable populations and areas. METHODS: Variables were identified from a comprehensive literature review and climate-health research in NYS. We obtained data from 2010 US Census Bureau and 2011 National Land Cover Database. We used principal component analysis to reduce correlated variables to fewer uncorrelated components, and then calculated the cumulative HVI for each census tract by summing up the scores across the components. The HVI was then mapped across NYS (excluding New York City) to display spatial vulnerability. The prevalence rates of heat stress were compared across HVI score categories. RESULTS: Thirteen variables were reduced to four meaningful components representing 1) social/language vulnerability; 2) socioeconomic vulnerability; 3) environmental/urban vulnerability; and 4) elderly/ social isolation. Vulnerability to heat varied spatially in NYS with the HVI showing that metropolitan areas were most vulnerable, with language barriers and socioeconomic disadvantage contributing to the most vulnerability. Reliability of the HVI was supported by preliminary results where higher rates of heat stress were collocated in the regions with the highest HVI. CONCLUSIONS: The NYS HVI showed spatial variability in heat vulnerability across the state. Mapping the HVI allows quick identification of regions in NYS that could benefit from targeted interventions. The HVI will be used as a planning tool to help allocate appropriate adaptation measures like cooling centers and issue heat alerts to mitigate effects of heat in vulnerable areas.


Subject(s)
Heat Stress Disorders/epidemiology , Hot Temperature/adverse effects , Surveys and Questionnaires , Vulnerable Populations , Humans , New York/epidemiology , Reproducibility of Results , Risk Factors , Socioeconomic Factors
4.
J Vet Pharmacol Ther ; 41(2): 184-194, 2018 Apr.
Article in English | MEDLINE | ID: mdl-28833212

ABSTRACT

Triazines are relatively new antiprotozoal drugs that have successfully controlled coccidiosis and equine protozoal myeloencephalitis. These drugs have favorably treated other protozoal diseases such as neosporosis and toxoplasmosis. In this article, we discuss the pharmacological characteristics of five triazines, toltrazuril, ponazuril, clazuril, diclazuril, and nitromezuril which are used in veterinary medicine to control protozoal diseases which include coccidiosis, equine protozoal myeloencephalitis, neosporosis, and toxoplasmosis.


Subject(s)
Antiprotozoal Agents/therapeutic use , Protozoan Infections, Animal/drug therapy , Triazines/therapeutic use , Acetonitriles/therapeutic use , Animals , Coccidiosis/drug therapy , Coccidiosis/veterinary , Encephalomyelitis, Equine/drug therapy , Encephalomyelitis, Equine/parasitology , Encephalomyelitis, Equine/veterinary , Horses , Nitriles/therapeutic use , Toxoplasmosis, Animal/drug therapy
5.
J Vet Pharmacol Ther ; 41(3): 374-377, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29383736

ABSTRACT

The pharmacokinetics of cefquinome were studied in healthy and Pasteurella multocida-infected rabbits after a single intramuscular (IM) injection at 2 mg/kg of its sulfate salt. Twelve female New Zealand white rabbits (2.0-2.5 kg) were used; six of them served as controls, and the other six had been infected with P. multocida; the experiments were conducted 1-2 days after nasal inoculation of P. multocida when rabbits showed the signs of respiratory infection. Plasma concentrations of cefquinome were determined using high-performance liquid chromatography. The values of elimination half-life, area under the curve, area under the first moment curve, and mean residence time were significantly lower in infected rabbits (0.48 hr, 4.54 hr*µg/ml, 3.63 hr* hr*µg/ml and 0.8 hr, respectively) than healthy rabbits (0.72 hr, 9.11 hr*µg/ml, 9.85 hr* hr*µg/ml and 1.1 hr, respectively), whereas total body clearance was significantly higher in infected than healthy rabbits. Therefore, P. multocida infection caused significant changes in some of the pharmacokinetic parameters of cefquinome in rabbits. These pharmacokinetic changes may affect dose regimen when used in P. multocida-infected rabbits.


Subject(s)
Cephalosporins/pharmacokinetics , Pasteurella Infections/veterinary , Pasteurella multocida , Rabbits , Animals , Area Under Curve , Cephalosporins/therapeutic use , Female , Half-Life , Pasteurella Infections/drug therapy , Pasteurella Infections/microbiology
6.
Am J Transplant ; 16(10): 2925-2931, 2016 10.
Article in English | MEDLINE | ID: mdl-27063452

ABSTRACT

The objective of this nationwide cohort study was to investigate the risk of peptic ulcer disease (PUD) in living liver donors (LDs). A total of 1333 LDs and 5332 matched nondonors were identified during 2003-2011. Hospitalized patients identified as LDs were assigned to the LD cohort, and the non-LD comparison cohort comprised age- and sex-matched nondonors. Cumulative incidences and hazard ratios (HRs) were calculated. The overall incidence of PUD was 1.74-fold higher in the LD cohort than in the non-LD cohort (2.14 vs. 1.48 per 1000 person-years). After adjustment for age, sex, monthly income and comorbidities, we determined that the LD cohort exhibited a higher risk of PUD than did the non-LD cohort (adjusted HR 1.74, 95% confidence interval [CI] 1.45-2.09). The incidence of PUD increased with age; the risk of PUD was 2.53-fold higher in patients aged ≥35 years (95% CI 2.14-2.99) than in those aged ≤34 years. LDs with comorbidities of osteopathies, chondropathies and acquired musculoskeletal deformities exhibited a higher risk of PUD (adjusted HR 3.93, 95% CI 2.64-5.86) compared with those without these comorbidities. LDs are associated with an increased risk of PUD after hepatectomy.


Subject(s)
Hepatectomy/adverse effects , Liver Transplantation , Living Donors/statistics & numerical data , Peptic Ulcer/epidemiology , Adult , Comorbidity , Female , Follow-Up Studies , Humans , Incidence , Longitudinal Studies , Male , Middle Aged , Peptic Ulcer/etiology , Prognosis , Taiwan/epidemiology
7.
Int J Obes (Lond) ; 39(12): 1750-6, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26119995

ABSTRACT

BACKGROUND: Leptin alleviates metabolic conditions such as insulin resistance and obesity, although the precise mechanism of action is unclear. Mitochondrial fusion/fission states affect energy balance, but the association between mitochondrial fusion and lipid metabolism is also unknown. The aim of this study was to determine whether mitochondrial fusion/fission state regulates lipid accumulation and to understand the role of leptin in mitochondrial function and its mechanism of action in metabolic regulation. METHODS: Primary mouse hepatocytes were isolated from C57BL/6J mice and treated with leptin (25 ng ml(-1)) for 3 days before determinations of mitochondrial morphology and fatty acid accumulation. Hyperglycemia in C57BL/6J mice was induced by providing a 30% fructose-rich diet (FRD) for 6 months, followed by intraperitoneal injections of leptin (1 mg kg(-1) per body weight) for 6 weeks (twice per week). RESULTS: Leptin triggered mitochondrial fusion and alleviated high glucose-induced fatty acid accumulation in primary hepatocytes by promoting mitochondrial fusion-associated transcription factor peroxisome proliferative-activated receptor-α and co-activator peroxisome proliferative-activated receptor-γ co-activator (PGC)-1α. In turn, these activate the fusion protein mitofusin 1 (Mfn-1). RNA silencing of Mfn-1 or PGC-1 blocked the inhibitory effect of leptin. Leptin treatment also elevated liver Mfn-1 and PGC-1α and improved lipid profiles in FRD mice. CONCLUSIONS: Mitochondrial fusion has a critical role in alleviating hepatic fatty acid accumulation. Leptin switches mitochondrial morphology via a PGC-1α-dependent pathway to improve hyperlipidemia.


Subject(s)
Fatty Liver/pathology , Hepatocytes/metabolism , Leptin/pharmacology , Liver/metabolism , Animals , Blotting, Western , Cells, Cultured , Disease Models, Animal , Gene Expression Regulation , Male , Mice , Mice, Inbred C57BL , Mitochondrial Dynamics
8.
Indoor Air ; 25(2): 157-67, 2015 Apr.
Article in English | MEDLINE | ID: mdl-24920413

ABSTRACT

This study assessed the relationship between teacher-reported symptoms and classroom carbon dioxide (CO2 ) concentrations. Previous studies have suggested that poor indoor ventilation can result in higher levels of indoor pollutants, which may affect student and teacher health. Ten schools (9 elementary, 1 combined middle/high school) in eight New York State school districts were visited over a 4-month period in 2010. Carbon dioxide concentrations were measured in classrooms over 48-h, and teachers completed surveys assessing demographic information and self-reported symptoms experienced during the current school year. Data from 64 classrooms (ranging from 1 to 9 per school) were linked with 68 teacher surveys (for four classrooms, two surveys were returned). Overall, approximately 20% of the measured classroom CO2 concentrations were above 1000 parts per million (ppm), ranging from 352 to 1591 ppm. In multivariate analyses, the odds of reporting neuro-physiologic (i.e., headache, fatigue, difficulty concentrating) symptoms among teachers significantly increased (OR = 1.30, 95% CI = 1.02-1.64) for every 100 ppm increase in maximum classroom CO2 concentrations and were non-significantly increased in classrooms with above-median proportions of CO2 concentrations greater than 1000 ppm (OR = 2.26, 95% CI = 0.72-7.12).


Subject(s)
Air Pollution, Indoor/analysis , Carbon Dioxide/analysis , Occupational Diseases/epidemiology , Occupational Exposure/analysis , Schools , Adult , Cognition Disorders/epidemiology , Fatigue/epidemiology , Female , Headache/epidemiology , Humans , Male , New York/epidemiology , Surveys and Questionnaires , Teaching , Ventilation
9.
J Dairy Sci ; 98(9): 6058-69, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26142860

ABSTRACT

Perioperative analgesic effects of oral firocoxib following cautery disbudding were investigated in preweaned calves. Twenty Holstein calves approximately 4 to 6wk old received a single oral dose of firocoxib, a nonsteroidal antiinflammatory, at 0.5mg/kg (n=10) or placebo (n=10) in a randomized controlled clinical trial. Responses, including ocular temperature determined by infrared thermography, pressure algometry measuring mechanical nociception threshold, and heart rate, were evaluated at 2, 4, 7, 8, and 24h after cornual nerve block and cautery disbudding. Blood samples were collected over 96h and analyzed for plasma cortisol and substance P concentrations by RIA. Additionally, ex vivo prostaglandin E2 concentrations were determined over a 72-h study period using an enzyme immunoassay. Data were analyzed using a linear mixed effects model with repeated measures. An inhibition of ex vivo prostaglandin E2 synthesis was observed from 12 to 48h following disbudding in calves treated with firocoxib. Cautery disbudding was associated with an increased nociception for the duration of sampling (24h). During the initial 24-h period following disbudding, no difference in response between treatment groups was noted. Following 24h, mean cortisol concentrations diverged between the 2 study groups with placebo-treated calves having increased cortisol concentrations at approximately 48h after disbudding. Furthermore, the overall integrated cortisol response as calculated as area under the effect curve tended to be reduced in firocoxib-treated calves. The prolonged effects of cautery dehorning require further investigation. Moreover, the effect of firocoxib on cortisol reduction observed in this study requires additional exploration.


Subject(s)
4-Butyrolactone/analogs & derivatives , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Sulfones/administration & dosage , 4-Butyrolactone/administration & dosage , Animals , Anti-Inflammatory Agents/blood , Cattle , Cautery/adverse effects , Female , Horns/surgery , Hydrocortisone/blood , Male , Neurotransmitter Agents/blood , Pain/prevention & control , Pain/veterinary , Substance P/blood
10.
Tech Coloproctol ; 17(4): 455-8, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23053443

ABSTRACT

Most perianal abscesses originate from infected anal glands at the base of the anal crypts. Most abscesses below are usually drained through perianal incision and can be treated successfully. However, when perianal abscesses extend to the high intrapelvic cavity, it may be inadequate treatment through a single route incision through a perianal approach. The aim of this technical note is to show that combined anterior ilioinguinal and perianal incisions may provide optimal surgical field and multiple drainages. Here, we report a 56-year-old male patient with perianal-originating parapsoas abscesses. Residual abscess still remained after initial perianal incision and drainage after 1-month treatment. We presented combined anterior ilioinguinal and perianal incision technique methods for proper drainage in this complicated case. No recurrent or residual abscess remained after 2 weeks of operation. So, combined anterior ilioinguinal incision is feasible for high-located perianal abscess.


Subject(s)
Abscess/surgery , Anal Canal/surgery , Anus Diseases/surgery , Drainage/methods , Inguinal Canal/surgery , Abscess/diagnostic imaging , Anus Diseases/diagnostic imaging , Combined Modality Therapy , Follow-Up Studies , Humans , Male , Middle Aged , Pelvic Infection/diagnostic imaging , Pelvic Infection/surgery , Risk Assessment , Severity of Illness Index , Tomography, X-Ray Computed/methods , Treatment Outcome
11.
Horm Metab Res ; 43(11): 766-73, 2011 Oct.
Article in English | MEDLINE | ID: mdl-22009371

ABSTRACT

p-Methoxycinnamic acid (p-MCA) is a cinnamic acid derivative that shows various pharmacologic actions such as hepatoprotective and antihyperglycemic activities. The present study was to elucidate the mechanisms by which p-MCA increases [Ca²âº]i and insulin secretion in INS-1 cells. p-MCA (100 µM) increased [Ca²âº]i in INS-1 cells. The p-MCA-induced insulin secretion and rise in [Ca²âº]i were markedly inhibited in the absence of extracellular Ca²âº or in the presence of an L-type Ca²âº channel blocker nimodipine. These results suggested that p-MCA increased Ca²âº influx via the L-type Ca²âº channels. Diazoxide, an ATP-sensitive K⁺ channel opener, did not alter p-MCA-induced insulin secretion, nor [Ca²âº]i response. In addition, p-MCA enhanced glucose-, glibenclamide-induced insulin secretion whereas it also potentiated the increase in insulin secretion induced by arginine, and Bay K 8644, an L-type Ca²âº channel agonist. Taken together, our results suggest that p-MCA stimulated insulin secretion from pancreatic ß-cells by increasing Ca²âº influx via the L-type Ca²âº channels, but not through the closure of ATP-sensitive K⁺ channels.


Subject(s)
Cinnamates/pharmacology , Hypoglycemic Agents/pharmacology , Insulin-Secreting Cells/drug effects , Insulin-Secreting Cells/metabolism , Insulin/metabolism , Animals , Arginine/metabolism , Calcium Channel Agonists/pharmacology , Calcium Channel Blockers/pharmacology , Calcium Channels, L-Type/chemistry , Calcium Signaling/drug effects , Cell Line , Glucose/metabolism , Insulin Secretion , KATP Channels/antagonists & inhibitors , Kinetics , Male , Membrane Transport Modulators/pharmacology , Perfusion , Rats , Rats, Sprague-Dawley , Secretory Pathway/drug effects
12.
Anim Genet ; 42(4): 421-7, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21749425

ABSTRACT

Transcriptome analysis using a cDNA microarray was performed to identify differentially expressed genes that are correlated with hatchability, and a new PCR-RFLP marker of high hatchability among the identified genes was observed. We used the cDNA microarray technique for gene expression profiling of the magnum epithelium of laying Tsaiya ducks, and several regulated genes associated with hatchability were found. The results of real-time PCR and Western blotting analysis confirmed that the mRNA and protein levels of ovomucoid in the magnum epithelium of animals in the low-hatchability group were significantly higher than the levels in the high-hatchability group (P < 0.05). Primers TovF1 and TovR1, designed according to the ovomucoid EST sequence, were used to amplify genomic DNA samples of different individual Tsaiya ducks, and sequence analysis of the amplified DNA products showed deletion among the ducks from the low-hatchability group. Primers TovF2 and TovR2 were used to perform PCR-RFLP analysis on the amplified DNA products to classify the ducks into +/+, +/- and -/- genotypes. The animals of +/+ and +/- genotypes were identified as having significantly higher hatchability than those of the -/- genotype (P < 0.05). In contrast, no differences were observed between genotypes in terms of fertility, duration of fertility, egg weight or total number of eggs. Our results indicated that a novel PCR-RFLP marker of high hatchability, an ovomucoid gene polymorphism, can be used as a genetic marker for marker-assisted selection to improve hatchability in Tsaiya ducks.


Subject(s)
Ducks/genetics , Genetic Variation , Ovomucin/genetics , Animals , Blotting, Western , Ducks/physiology , Gene Expression Profiling , Genetic Markers/genetics , Genotype , Oligonucleotide Array Sequence Analysis , Polymorphism, Restriction Fragment Length , Reproduction/genetics , Reverse Transcriptase Polymerase Chain Reaction
13.
Eur Respir J ; 36(6): 1355-61, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20516056

ABSTRACT

Significant heterogenity of stage IB (sixth edition of the TNM staging system) nonsmall cell lung cancer (NSCLC) has been identified, and further subclassification according to tumour size has been proposed. The aim of this study is to evaluate the prognostic factors in patients with resected stage IB NSCLC > 3 cm. From January 1980 to December 2000, 525 patients underwent surgical resection for stage IB NSCLC > 3 cm at Taipei Veterans General Hospital, Taipei, Taiwan. The clinicopathological characteristics of these patients were retrospectively reviewed. The 5- and 10-yr overall survival rates were 44.9% and 27.3%, respectively. Age (p < 0.001), tumour size (p = 0.002), extent of pulmonary resection (p = 0.002), histological type (p = 0.005) and number of mediastinal lymph nodes dissected/sampled (p = 0.004) were significant predictors for overall survival in multivariate analysis. Patients with tumour size >7 cm, or > 5 to ≤ 7 cm, had a worse survival than those with tumour size > 3 to ≤ 5 cm. However, visceral pleural invasion did not influence overall survival. Stage IB NSCLC with a diameter > 3 cm may be subclassified according to tumour size regardless of visceral pleural invasion.


Subject(s)
Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Aged , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/surgery , Female , Humans , Lung Neoplasms/mortality , Lung Neoplasms/surgery , Lymph Nodes/pathology , Lymph Nodes/surgery , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Pleura/pathology , Pleura/surgery , Prognosis , Retrospective Studies , Smoking/adverse effects , Survival Rate
14.
J Vet Pharmacol Ther ; 33(4): 315-22, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20646191

ABSTRACT

Fleas are significant ectoparasites of small animals. They can be a severe irritant to animals and serve as a vector for a number of infectious diseases. In this article, we discuss the pharmacological characteristics of four insect nicotinic acetylcholine receptor (nAChR) agonists used as flea adulticides in dogs and cats, which include three neonicotinoids (imidacloprid, nitenpyram, and dinotefuran) and a macrocyclic lactone (spinosad). Insect nAChR agonists are one of the most important classes of insecticides, which are used to control sucking insects on both plants and animals. These novel compounds provide a new approach for practitioners to safely and effectively eliminate adult fleas.


Subject(s)
Insecticides , Nicotinic Agonists , Siphonaptera , Animals , Cats , Dogs , Drug Combinations , Guanidines/adverse effects , Guanidines/chemistry , Guanidines/pharmacokinetics , Imidazoles/adverse effects , Imidazoles/chemistry , Imidazoles/pharmacokinetics , Insect Vectors , Insecticides/adverse effects , Insecticides/chemistry , Insecticides/pharmacokinetics , Macrolides/adverse effects , Macrolides/chemistry , Macrolides/pharmacokinetics , Neonicotinoids , Nicotinic Agonists/adverse effects , Nicotinic Agonists/chemistry , Nicotinic Agonists/pharmacokinetics , Nitro Compounds/adverse effects , Nitro Compounds/chemistry , Nitro Compounds/pharmacokinetics , Pyridines/adverse effects , Pyridines/chemistry , Pyridines/pharmacokinetics
15.
QJM ; 113(9): 643-650, 2020 Sep 01.
Article in English | MEDLINE | ID: mdl-32186731

ABSTRACT

OBJECTIVE: Air pollution had been reported to be associated with the reproductive health of women. However, the association of particulate matter (PM) and acid gases air pollution with premenstrual syndrome (PMS) warrants investigation. This study investigated the effects of air pollution on PMS risk. POPULATION: We combined data from the Taiwan Air Quality-Monitoring Database and the Longitudinal Health Insurance Database. In total, an observational cohort of 85 078 Taiwanese women not diagnosed as having PMS. METHODS: Air pollutant concentrations were grouped into four levels based on the concentration quartiles of several types of air pollutants. MAIN OUTCOME MEASURES: We then applied univariable and multivariable Cox proportional hazard regression models to assess PMS risk in association with each pollutant type. RESULTS: Women exposed to Q4-level SO2 exhibited a 7.77 times higher PMS risk compared with those to Q1-level SO2 (95% confidence interval [CI] = 6.22-9.71). Women exposed to Q4-level NOx exhibited a 2.86 times higher PMS risk compared with those exposed to Q1-level NOx (95% CI = 2.39-3.43). Women exposed to Q4-level NO exhibited a 3.17 times higher PMS risk compared with women exposed to Q1-level NO (95% CI = 2.68-3.75). Finally, women exposed to Q4-level PM with a ≤2.5-µm diameter (PM2.5) exhibited a 3.41 times higher PMS risk compared with those exposed to Q1-level PM2.5 (95% CI = 2.88-4.04). CONCLUSIONS: High incidences of PMS were noted in women who lived in areas with higher concentrations of SO2, NOx, NO, NO2 and PM2.5.


Subject(s)
Air Pollutants/analysis , Air Pollution/adverse effects , Particulate Matter/analysis , Premenstrual Syndrome/epidemiology , Adolescent , Adult , Air Pollution/statistics & numerical data , Atmosphere/chemistry , Cohort Studies , Female , Humans , Hydrogen-Ion Concentration , Middle Aged , Multivariate Analysis , Nitrates/analysis , Ozone/analysis , Proportional Hazards Models , Sulfates/analysis , Taiwan/epidemiology , Young Adult
16.
Thorax ; 64(12): 1082-9, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19778933

ABSTRACT

BACKGROUND: Metastasis is the most common cause of disease failure and mortality for non-small cell lung cancer (NSCLC) after surgical resection. Snail and TWIST1 are epithelial-mesenchymal transition (EMT) regulators which induce metastasis. Intratumoral hypoxia followed by stabilisation of hypoxia-inducible factor 1alpha (HIF-1alpha) promotes metastasis through regulation of certain EMT regulators. The aim of this study was to evaluate the prognostic value of HIF-1alpha, TWIST1 and Snail expression in patients with resectable NSCLC. METHODS: A retrospective analysis of 87 patients with resectable NSCLC from Taipei Veterans General Hospital between 2003 and 2004 was performed using immunohistochemistry to analyse HIF-1alpha, TWIST1 and Snail expression. The association between HIF-1alpha, TWIST1 and Snail expression and patients' overall and recurrence-free survivals was investigated. RESULTS: Overexpression of HIF-1alpha, TWIST1 or Snail was shown in 32.2%, 36.8% and 55.2% of primary tumours, respectively. Overexpression of HIF-1alpha, TWIST1 or Snail in primary NSCLCs was associated with a shorter overall survival (p = 0.005, p = 0.026, p = 0.009, respectively), and overexpression of HIF-1alpha was associated with a shorter recurrence-free survival (p = 0.016). We categorised the patients into four groups according to the positivity of HIF-1alpha/TWIST1/Snail to investigate the accumulated effects of these markers on survival. Co-expression of more than two markers was an independent prognostic indicator for both recurrence-free survival and overall survival (p = 0.004 and p<0.001, respectively, by multivariate Cox proportional hazards model). CONCLUSIONS: Co-expression of more than two markers from HIF-1alpha, TWIST1 and Snail is a significant prognostic predictor in patients with NSCLC.


Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/diagnosis , Lung Neoplasms/diagnosis , Neoplasm Proteins/metabolism , Aged , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/therapy , Chemotherapy, Adjuvant , Epidemiologic Methods , Female , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Male , Middle Aged , Neoplasm Staging , Nuclear Proteins/metabolism , Prognosis , Snail Family Transcription Factors , Transcription Factors/metabolism , Treatment Outcome , Twist-Related Protein 1/metabolism
17.
Thorax ; 64(3): 192-6, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19252018

ABSTRACT

OBJECTIVE: Resection is the best treatment for patients with stage I non-small cell lung cancer (NSCLC). Patterns of disease recurrence after complete resection in stage I NSCLC have not been well demonstrated. The aim of this study was to evaluate the prognostic predictors of post-recurrence survival in patients with resected stage I NSCLC with local recurrence. METHODS: The clinicopathological characteristics of 123 patients with local recurrence after complete resection of stage I NSCLC in Taipei Veterans General Hospital between 1980 and 2000 were retrospectively reviewed. Post-recurrence survival and their predictors were analysed. RESULTS: The patterns of local recurrence included local only in 74 (60.2%) and both local and distant in 49 (39.8%) patients. The 1 and 2 year post-recurrence survival rates for the 74 patients with local only recurrence were 48.7% and 17.6%, respectively. Tumour size (p = 0.033) and treatment for initial recurrence (p<0.001) were significant predictors for post-recurrence survival in 74 patients with local only recurrence in univariate analyses. The hazard of death was greater in patients with larger tumour size. Treatment for initial recurrence (p = 0.001) was still a significant prognostic indicator in multivariate analyses. Patients who underwent reoperation after local recurrence survived longer than those who received chemotherapy and/or radiotherapy and those that received no treatment. CONCLUSIONS: Treatment for initial recurrence is a prognostic predictor for post-recurrence survival in resected stage I NSCLC with local recurrence. Complete surgical resection should be considered in selected candidates with resectable local recurrent disease.


Subject(s)
Carcinoma, Non-Small-Cell Lung/mortality , Lung Neoplasms/mortality , Neoplasm Recurrence, Local/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/surgery , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Prognosis , Tumor Burden
18.
Mol Cell Endocrinol ; 299(2): 194-203, 2009 Feb 27.
Article in English | MEDLINE | ID: mdl-19063936

ABSTRACT

TRPM4 is a Ca(2+)-activated non-selective cation (CAN) channel that functions in cell depolarization, which is important for Ca(2+) influx and insulin secretion in pancreatic beta-cells. We investigated TRPM4 expression and function in the beta-cell lines HIT-T15 (hamster), RINm5F (rat), beta-TC3 (mouse), MIN-6 (mouse) and the alpha-cell line INR1G9 (hamster). By RT-PCR, we identified TRPM4 transcripts in alpha- and beta-cells. Patch-clamp recordings with increasing Ca(2+) concentrations resulted in a dose-dependent activation of TRPM4 with the greatest depolarizing currents recorded from hamster-derived cells. Further, Ca(2+) imaging experiments revealed that inhibition of TRPM4 by a dominant-negative effect significantly decreased the magnitude of the Ca(2+) signals generated by agonist stimulation compared to control cells. The decrease in the [Ca(2+)](i) resulted in reduced insulin secretion. Our data suggest that depolarizing currents generated by TRPM4 are an important component in the control of intracellular Ca(2+) signals necessary for insulin secretion and perhaps glucagon from alpha-cells.


Subject(s)
Calcium Signaling , Insulin-Secreting Cells/metabolism , Insulin/metabolism , TRPM Cation Channels/metabolism , Animals , Calcium/pharmacology , Calcium Signaling/drug effects , Cell Line , Cricetinae , Glucose/pharmacology , Glyburide/pharmacology , Humans , Insulin Secretion , Insulin-Secreting Cells/drug effects , Mice , Potassium Chloride/pharmacology , Rats , TRPM Cation Channels/antagonists & inhibitors
19.
J Endocrinol Invest ; 32(2): 139-46, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19411812

ABSTRACT

AIM: The aim of this study was to evaluate the intra- observer and inter-observer reproducibility of 3-dimensional (3D) power Doppler ultrasonography with the virtual organ computer-aided analysis (VOCAL) program for measuring thyroid volume and vascular indices in patients with diffuse thyroid disorders. MATERIALS AND METHODS: Patients with diffuse goiters were examined by 3D ultrasonography from August 2005 to July 2006. The parameters for vascular assessment included the vascularization index (VI), flow index (FI), vascularization-flow index (VFI), and thyroid size, and were obtained using the VOCAL program. This program used plane A and a 30 degrees rotational step. Intra-observer and inter-observer repeatability are presented as intra-class correlation coefficient (intra-CC) and inter-class correlation coefficient (inter-CC), with values >0.70 being acceptable. RESULTS: Sixty-three patients in total were enrolled for this study, including 19 patients with simple goiter and 44 patients with autoimmune thyroid disease (AITD) (23 Graves' disease, 21 Hashimoto's thyroiditis). Thyroid volume and 3 vascular indices showed excellent reproducibility in the AITD group (intra- CC>0.9373 and inter-CC>0.8763) and its subgroups. The VI had excellent consistent reproducibility in the simple goiter group (intra-CC>0.8987 and inter-CC>0.8881), but the other parameters did not. CONCLUSIONS: Based on this study, 3D power Doppler ultrasonography with the VOCAL program is a reliable tool for evaluating diffuse thyroid disorders due to an autoimmune process. The VI is the most reliable parameter.


Subject(s)
Image Processing, Computer-Assisted/methods , Imaging, Three-Dimensional/methods , Thyroid Diseases/diagnostic imaging , Ultrasonography, Doppler/methods , Adolescent , Adult , Aged , Child , Goiter/diagnostic imaging , Graves Disease/diagnostic imaging , Hashimoto Disease/diagnostic imaging , Humans , Middle Aged , Observer Variation , Reproducibility of Results , Retrospective Studies , Thyroid Gland/blood supply , User-Computer Interface
20.
Thorac Cardiovasc Surg ; 57(7): 434-6, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19795336

ABSTRACT

A centrally located large pulmonary arteriovenous malformation (PAVM) with aneurysmal formation is uncommon and the optimal treatment remains unclear. Here we report a 63-year-old female with a large PAVM located in the pulmonary hilum presenting with dyspnea and a brain abscess. A muscle-sparing thoracotomy with lobectomy of the left upper lobe was successfully performed under the guidance of three-dimensional reconstruction imaging of the thoracic vasculature.


Subject(s)
Aneurysm/etiology , Arteriovenous Malformations/complications , Pulmonary Artery/abnormalities , Pulmonary Veins/abnormalities , Aneurysm/diagnostic imaging , Aneurysm/surgery , Arteriovenous Malformations/diagnostic imaging , Arteriovenous Malformations/surgery , Brain Abscess/etiology , Dyspnea/etiology , Female , Humans , Imaging, Three-Dimensional , Middle Aged , Pulmonary Artery/diagnostic imaging , Pulmonary Artery/surgery , Pulmonary Veins/diagnostic imaging , Pulmonary Veins/surgery , Radiographic Image Interpretation, Computer-Assisted , Surgery, Computer-Assisted , Thoracotomy/methods , Tomography, X-Ray Computed , Treatment Outcome
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