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Physiological Research 2003To specify the role of individual cytokines in the immune response to pyrogens, isolated and cultivated human peripheral blood mononuclear cells (PBMC) were used for the...
To specify the role of individual cytokines in the immune response to pyrogens, isolated and cultivated human peripheral blood mononuclear cells (PBMC) were used for the experiments. Different pyrogens (lipopolysaccharide from Escherichia coli - LPS and live Borrelia afzelii) were applied and the time course of changes in concentrations of different cytokines in the medium was followed using the ELISA method. It was found that nonstimulated human PBMC proliferate under in vitro conditions and produce IL-6, TNF-alpha, IL-10 and finally also IL-1 beta. Productions of IL-12 and INF-gamma are not changed. Proliferation of PBMC is potentiated after incubation with LPS or live Borrelia. PBMC stimulated by LPS increase the net production (stimulated minus unstimulated) of IL-1 beta and TNF-alpha significantly, while production of IL-6 was smaller. A delayed increase in the production of IL-10 was also observed. Productions of IL-12 and INF-gamma were not influenced. In contrast to LPS, stimulation of PBMC with live Borrelia, increases also the production of IL-12 and IFN-gamma, besides IL-1 beta, TNF-alpha, IL-6 and IL-10. Productions of IL-1 beta, IL-6 and TNF alpha increased immediately after incubation with both LPS and Borrelia, while productions of IL-12 and INF-gamma begin to increase 8 hours and production of IL-10 12 hours after stimulation. Data indicate that stimulation with different pyrogens may activate the cells of the immune cascade in a different way. Stimulation of BPMC by LPS seems to activate the initial steps of the immune response (macrophages and granulocytes) only, while infection with live Borrelia also stimulates the later phase of the immune response, probably due to effect of initially produced cytokines.
Topics: Adult; Aged; Borrelia burgdorferi Group; Cell Division; Cells, Cultured; Cytokines; Female; Humans; Interferon-gamma; Interleukin-1; Interleukin-10; Interleukin-12; Interleukin-6; Leukocytes, Mononuclear; Lipopolysaccharides; Male; Middle Aged; Tumor Necrosis Factor-alpha
PubMed: 14964289
DOI: No ID Found -
The Journal of Pharmacology and... Feb 2021Integrated in silico chemical clustering and melatonin receptor molecular modeling combined with in vitro 2-[I]-iodomelatonin competition binding were used to identify...
Integrated in silico chemical clustering and melatonin receptor molecular modeling combined with in vitro 2-[I]-iodomelatonin competition binding were used to identify carbamate insecticides with affinity for human melatonin receptor 1 (hMT) and human melatonin receptor 2 (hMT). Saturation and kinetic binding studies with 2-[I]-iodomelatonin revealed lead carbamates (carbaryl, fenobucarb, bendiocarb, carbofuran) to be orthosteric ligands with antagonist apparent efficacy at hMT and agonist apparent efficacy at hMT Furthermore, using quantitative receptor autoradiography in coronal brain slices from C3H/HeN mice, carbaryl, fenobucarb, and bendiocarb competed for 2-[I]-iodomelatonin binding in the suprachiasmatic nucleus (SCN), paraventricular nucleus of the thalamus (PVT), and pars tuberalis (PT) with affinities similar to those determined for the hMT receptor. Carbaryl (10 mg/kg i.p.) administered in vivo also competed ex vivo for 2-[I]-iodomelatonin binding to the SCN, PVT, and PT, demonstrating the ability to reach brain melatonin receptors in C3H/HeN mice. Furthermore, the same dose of carbaryl given to C3H/HeN mice in constant dark for three consecutive days at subjective dusk (circadian time 10) phase-advanced circadian activity rhythms (mean = 0.91 hours) similar to melatonin (mean = 1.12 hours) when compared with vehicle (mean = 0.04 hours). Carbaryl-mediated phase shift of overt circadian activity rhythm onset is likely mediated via interactions with SCN melatonin receptors. Based on the pharmacological actions of carbaryl and other carbamate insecticides at melatonin receptors, exposure may modulate time-of-day information conveyed to the master biologic clock relevant to adverse health outcomes. SIGNIFICANCE STATEMENT: In silico chemical clustering and molecular modeling in conjunction with in vitro bioassays identified several carbamate insecticides (i.e., carbaryl, carbofuran, fenobucarb, bendiocarb) as pharmacologically active orthosteric melatonin receptor 1 and 2 ligands. This work further demonstrated that carbaryl competes for melatonin receptor binding in the master biological clock (suprachiasmatic nucleus) and phase-advances overt circadian activity rhythms in C3H/HeN mice, supporting the relevance of circadian effects when interpreting toxicological findings related to carbamate insecticide exposure.
Topics: Animals; Binding Sites; Brain; CHO Cells; Carbamates; Circadian Rhythm; Cricetinae; Cricetulus; Humans; Insecticides; Male; Mice; Molecular Docking Simulation; Protein Binding; Receptors, Melatonin
PubMed: 33203660
DOI: 10.1124/jpet.120.000065 -
3 Biotech May 2017Food security and safety are the major concern in ever expanding human population on the planet earth. Each and every year insect pests cause a serious damage in... (Review)
Review
Food security and safety are the major concern in ever expanding human population on the planet earth. Each and every year insect pests cause a serious damage in agricultural field that cost billions of dollars annually to farmers. The loss in term of productivity and high cost of chemical pesticides enhance the production cost. Irrespective use of chemical pesticides (such as Benzene hexachloride, Endosulfan, Aldicarb, and Fenobucarb) in agricultural field raised several types of environmental issues. Furthermore, continuous use of chemical pesticides creates a selective pressure which helps in emerging of resistance pest. These excess chemical pesticide residues also contaminate the environment including the soil and water. Therefore, the biological control of insect pest in the agricultural field gains more importance due to food safety and environment friendly nature. In this regard, bacterial insecticides offer better alternative to chemical pesticides. It not only helps to establish food security through fighting against insect pests but also ensure the food safety. In this review, we have categorized insect pests and the corresponding bacterial insecticides, and critically analyzed the importance and mode of action of bacterial pesticides. We also have summarized the use of biopesticides in integrated pest management system. We have tried to focus the future research area in this field for the upcoming scientists.
PubMed: 28444605
DOI: 10.1007/s13205-017-0717-6 -
NPJ Precision Oncology Nov 2023Acquired drug resistance remains a major problem across oncogene-addicted cancers. Elucidation of mechanisms of resistance can inform rational treatment strategies for...
Acquired drug resistance remains a major problem across oncogene-addicted cancers. Elucidation of mechanisms of resistance can inform rational treatment strategies for patients relapsing on targeted therapies while offering insights into tumor evolution. Here, we report acquired MET amplification as a resistance driver in a ROS1-rearranged lung adenocarcinoma after sequential treatment with ROS1 inhibitors. Subsequent combination therapy with lorlatinib plus capmatinib, a MET-selective inhibitor, induced intracranial and extracranial tumor response. At relapse, sequencing of the resistant tumor revealed a MET D1246N mutation and loss of MET amplification. We performed integrated molecular analyses of serial tumor and plasma samples, unveiling dynamic alterations in the ROS1 fusion driver and MET bypass axis at genomic and protein levels and the emergence of polyclonal resistance. This case illustrates the complexity of longitudinal tumor evolution with sequential targeted therapies, highlighting challenges embedded in the current precision oncology paradigm and the importance of developing approaches that prevent resistance.
PubMed: 37923925
DOI: 10.1038/s41698-023-00464-y -
Experimental Physiology Feb 2023What is the central question of this study? What are the independent effects of air temperature and humidity on performance, physiological and perceptual responses...
NEW FINDINGS
What is the central question of this study? What are the independent effects of air temperature and humidity on performance, physiological and perceptual responses during endurance exercise? What is the main finding and its importance? When examined independently, elevated air temperature increased heat strain and impaired aerobic exercise performance, but to a lesser extent than has been reported previously. These findings highlight the importance of absolute humidity relative to temperature when exercising or working under severe heat stress.
ABSTRACT
Many studies have reported that ambient heat stress increases physiological and perceptual strain and impairs endurance exercise, but effects of air temperature per se remain almost unexamined. Most studies have used matched relative humidity, thereby exponentially increasing absolute humidity (water content in air) concurrently with temperature. Absolute (not relative) humidity governs evaporative rate and is more important at higher work rates and air temperatures. Therefore, we examined the independent effects of air temperature and humidity on performance, thermal, cardiovascular and perceptual measures during endurance exercise. Utilizing a crossover design, 14 trained participants (7 females) completed 45 min fixed-intensity cycling (70% ) followed by a 20-km time trial in each of four environments: three air temperatures at matched absolute humidity (Cool, 18°C; Moderate, 27°C; and Hot, 36°C; at 1.96 kPa, air velocity ∼4.5 m/s), and one at elevated humidity (Hot Humid, 36°C at 3.92 kPa). Warmer air caused warmer skin (0.5°C/°C; P < 0.001), higher heart rate (1 bpm/°C; P < 0.001), sweat rate (0.04 l/h/°C; P < 0.001) and thermal perceptions during fixed-intensity exercise, but minimally affected core temperature (<0.01°C/°C; P = 0.053). Time-trial performance was comparable between Cool and Moderate (95% CI: -1.4, 5.9%; P = 0.263), but 3.6-6% slower in Hot (95% CI: ±2.4%; P ≤ 0.006). Elevated humidity increased core temperature (P < 0.001), perceived temperature and discomfort but not skin temperature or heart rate, and reduced mean blood pressure (P = 0.046) during fixed-intensity exercise. Elevated humidity impaired time-trial performance by 3.4% (95% CI: ±2.2%; P = 0.006). In conclusion, these findings quantify the importance of absolute humidity alongside air temperature when exercising under severe heat stress.
Topics: Female; Humans; Body Temperature; Body Temperature Regulation; Heart Rate; Heat Stress Disorders; Hot Temperature; Humidity; Temperature; Cross-Over Studies
PubMed: 36537856
DOI: 10.1113/EP090969 -
Environmental Science and Pollution... Mar 2023The extraction of 21 insecticides and 5 metabolites was performed using an optimized and validated QuEChERS protocol that was further used for the quantification...
The extraction of 21 insecticides and 5 metabolites was performed using an optimized and validated QuEChERS protocol that was further used for the quantification (GC-MS/MS) in several seafood matrices (crustaceans, bivalves, and fish-mudskippers). Seven species, acquired from Hong Kong and Macao wet markets (a region so far poorly monitored), were selected based on their commercial importance in the Indo-Pacific region, market abundance, and affordable price. Among them, mussels from Hong Kong, together with mudskippers from Macao, presented the highest insecticide concentrations (median values of 30.33 and 23.90 ng/g WW, respectively). Residual levels of fenobucarb, DDTs, HCHs, and heptachlors were above the established threshold (10 ng/g WW) for human consumption according to the European and Chinese legislations: for example, in fish-mudskippers, DDTs, fenobucarb, and heptachlors (5-, 20- and tenfold, respectively), and in bivalves, HCHs (fourfold) had higher levels than the threshold. Risk assessment revealed potential human health effects (e.g., neurotoxicity), especially through fish and bivalve consumption (non-carcinogenic risk; ΣHQ > 1), and a potential concern of lifetime cancer risk development through the consumption of fish, bivalves, and crustaceans collected from these markets (carcinogenic risk; ΣTCR > 10). Since these results indicate polluted regions, where the seafood is collected/produced, a strict monitoring framework should be implemented in those areas to improve food quality and safety of seafood products.
Topics: Animals; Bivalvia; Fishes; Food Contamination; Insecticides; Risk Assessment; Seafood; Tandem Mass Spectrometry; Water Pollutants, Chemical
PubMed: 36515882
DOI: 10.1007/s11356-022-24413-7 -
PloS One 2017Bioremediation of pollutants is a major concern worldwide, leading to the research of new processes to break down and recycle xenobiotics and environment contaminating...
Bioremediation of pollutants is a major concern worldwide, leading to the research of new processes to break down and recycle xenobiotics and environment contaminating polymers. Among them, carbamates have a very broad spectrum of uses, such as toxinogenic pesticides or elastomers. In this study, we mined the bovine rumen microbiome for carbamate degrading enzymes. We isolated 26 hit clones exhibiting esterase activity, and were able to degrade at least one of the targeted polyurethane and pesticide carbamate compounds. The most active clone was deeply characterized. In addition to Impranil, this clone was active on Tween 20, pNP-acetate, butyrate and palmitate, and on the insecticide fenobucarb. Sequencing and sub-cloning of the best target revealed a novel carboxyl-ester hydrolase belonging to the lipolytic family IV, named CE_Ubrb. This study highlights the potential of highly diverse microbiota such as the ruminal one for the discovery of promiscuous enzymes, whose versatility could be exploited for industrial uses.
Topics: Animals; Carbamates; Cattle; Metagenomics
PubMed: 29240834
DOI: 10.1371/journal.pone.0189201 -
PloS One 2022Pesticide residue in food, especially in vegetables, is one of the important parameters to assess food safety. This study evaluates the pesticide use in vegetables from...
Pesticide residue in food, especially in vegetables, is one of the important parameters to assess food safety. This study evaluates the pesticide use in vegetables from two provinces in Central Vietnamand and present data on pesticides detected in vegetables sampled from the sites. The potential health risk associated with the contamination of four commonly used pesticides in different vegetables is also discussed. Both household surveys and monitoring campaigns were conducted. The survey showed that improper pesticide application, storage, and waste disposal prevailed at the study sites. Only 20% of the respondent were aware of pesticide toxicity. As a result, pesticides were detected in 81% out of 290 vegetable samples collected at harvesting time. Up to 23% of samples had pesticide residues above the Maximum Residue Limit values. The highest total pesticide concentration quantified in vegetables in Thua Thien Hue was 11.9 mg/kg (green onions), and in Quang Binh was 38.6 mg/kg (mustard greens). Median residue levels of individual pesticides in vegetables ranged from 0.007 to 0.037 mg/kg. Among the ten target pesticides, cypermethrin, difenoconazole, and fenobucarb were detected at the highest frequencies (72%, 41%, and 37%, respectively). Pesticide residues varied between seasons at both study provinces. Pesticide contamination in the wet season was significantly higher than in the dry season. This study also discovered a potential health risk associated with fipronil residues in vegetables in Thua Thien Hue province. The paper provides recommendations for mitigation measures (both technological and social) in reducing potential health risks linked to pesticide use in vegetables in the region.
Topics: Food Contamination; Fruit; Pesticide Residues; Pesticides; Vegetables; Vietnam
PubMed: 35696374
DOI: 10.1371/journal.pone.0269789 -
Clinical Toxicology (Philadelphia, Pa.) Sep 2016Highly hazardous organophosphorus (OP) insecticides are responsible for most pesticide poisoning deaths. As they are removed from agricultural practice, they are often...
BACKGROUND
Highly hazardous organophosphorus (OP) insecticides are responsible for most pesticide poisoning deaths. As they are removed from agricultural practice, they are often replaced by carbamate insecticides of perceived lower toxicity. However, relatively little is known about poisoning with these insecticides.
METHODS
We prospectively studied 1288 patients self-poisoned with carbamate insecticides admitted to six Sri Lankan hospitals. Clinical outcomes were recorded for each patient and plasma carbamate concentration measured in a sample to confirm the carbamate ingested.
FINDINGS
Patients had ingested 3% carbofuran powder (719), carbosulfan EC25 liquid (25% w/v, 389), or fenobucarb EC50 liquid (50% w/v, 127) formulations, carbamate insecticides of WHO Toxicity Classes Ib, II, and II, respectively. Intubation and ventilation was required for 183 (14.2%) patients while 71 (5.5%) died. Compared with carbofuran, poisoning with carbosulfan or fenobucarb was associated with significantly higher risk of death [carbofuran 2.2%; carbosulfan 11.1%, OR 5.5 (95% CI 3.0-9.8); fenobucarb 6.3%, OR 3.0 (1.2-7.1)] and intubation [carbofuran 6.1%; carbosulfan 27.0%, OR 5.7 (3.9-8.3); fenobucarb 18.9%, OR 3.6 (2.1-6.1)]. The clinical presentation and cause of death did not differ markedly between carbamates. Median time to death was similar: carbofuran 42.3 h (IQR 5.5-67.3), carbosulfan 21.3 h (11.5-71.3), and fenobucarb 25.3 h (17.3-72.1) (p = 0.99); no patients showed delayed onset of toxicity akin to the intermediate syndrome seen after OP insecticide poisoning. For survivors, median duration of intubation was 67.8 h (IQR 27.5-118.8) with no difference in duration between carbamates. Reduced GCS at presentation was associated with worse outcome although some patients with carbosulfan died after presentation with normal GCS.
CONCLUSIONS
We did not find carbamate insecticide self-poisoning to vary markedly according to the carbamate ingested although the case fatality varied according to the concentration and formulation of the insecticide. Carbamate poisoning did not appear to be much less toxic than poisoning with some liquid OP insecticide formulations, e.g., chlorpyrifos EC40, that we have previously noted in these same hospitals (Lancet 2005, 366:1452-1459; QJM 2006, 99:513-522). Replacement of WHO Class II Toxicity OP insecticides in agriculture with high-strength liquid carbamate formulations may not substantially reduce case fatality after pesticide poisoning and, therefore, global suicide rates.
Topics: Animals; Carbamates; Cohort Studies; Humans; Insecticides; Lethal Dose 50; Molecular Structure; Mortality; Poisoning; Prospective Studies; Sri Lanka; Suicide; Treatment Outcome; Suicide Prevention
PubMed: 27252029
DOI: 10.1080/15563650.2016.1187735