The Effect of a “Zero” Magnetic Field on the Production of Reactive Oxygen Species in Neutrophils

Exposure of mouse peritoneal neutrophils to hypomagnetic conditions (magnetic shielding, a residual static magnetic field of 20 nT) for 1.5 h decreased the level of intracellular reactive oxygen species as recorded by changes in the fluorescence intensity of 2,7-dichlorodihydrofluorescein and dihydrorhodamine 123 oxidation products. The effect of a hypomagnetic field was similarly observed after adding a respiratory burst activator (the formylated peptide N-formyl–Met–Leu–Phe or phorbol 12-meristate-13-acetate) to a low concentration.     

Gender and Age Differences in the Suppressive Effect of a 50 Hz Electric Field on the Immobilization-Induced Increase of Plasma Glucocorticoid in Mice

We developed an experimental system to characterize the suppressive effect of extremely low-frequency (ELF) electric fields (EFs) on the stress response. We assessed differences in the EF effects by age and gender. Control, EF-alone, immobilization-alone, and co-treated groups were subjected to an EF (50 Hz, 10 kV/m). Co-treated mice were exposed to the EF for 60 min, with immobilization during the latter half. Our results indicate that the suppressive effects of ELF EFs on the stress response in immobilized mice occur regardless of gender or age. As stress plays an important role in the onset and progression of various diseases, these findings may have broad implications for understanding the efficacy of EFs in animal, and perhaps human, health. Bioelectromagnetics. 2020;41:156–163. © 2019 Bioelectromagnetics Society.     

Effect of Long-Term Exposure to a Randomly Varied 50 Hz Power Frequency Magnetic Field on the Fertility of the Mouse

A double blind study on BALB/c mice was conducted to examine the effects of extremely low-frequency electromagnetic fields on fertility. The mice were continuously exposed or sham-exposed from conception for two generations to magnetic fields varying between 0.5 and 77?μT. Biological parameters related to fertility were evaluated. Serum testosterone levels and mass of testes and adrenals were determined. No significant difference was found between the sham-exposed and exposed groups for all the biological endpoints, except for sperm motility. A significant difference between the two groups was found prior to the swim-up test with quantitative analysis of sperm motility as well as after the swim-up test for quantitative and qualitative analysis of sperm motility. ELF-EMFs significantly decreased the number of living sperm and the quality of movement of sperm, although these adversities did not impact on the outcome of the other parameters investigated.     

The Effect of a Weak Static Magnetic Field in the Range of Magnitudes from a “Zero” Field (0.01 μT) to 100 μT on the Production of Reactive Oxygen Species in Nonactivated Neutrophils

Biophysics - It was shown that 40-min exposure of peritoneal neutrophils to hypomagnetic conditions (with a residual field of 0.01 μT) caused a significant (25%) decrease in the intensity of...     

Circadian Time‐Effect of Orally Administered Loratadine on Plasma Pharmacokinetics in Mice

Little is known about the chronopharmacokinetics of loratadine, a long‐acting tricyclic antihistamine H₁ widely used in the treatment of allergic diseases. Hence, the pharmacokinetics of loratadine and its major metabolite, desloratadine, were investigated after a 20 mg/kg dose of loratadine had been orally administered to comparable groups of mice (n=33), synchronized for three weeks to 12 h light (rest span)/12 h dark (activity span). The drug was administered at three different circadian times (1, 9, and 17 h after light onset [HALO]). Multiple blood samples were collected over 48 h, and plasma concentrations of loratadine and desloratadine were determined by high performance liquid chromatography. There were no significant differences in T_max of loratadine and desloratadine between treatment‐time different groups. However, the elimination half‐life (t1/2) of the parent compound and its metabolite was significantly longer (p<0.01) following administration at 9 HALO (t1/2 loratadine and desloratadine 5.62 and 4.08 h at 9 HALO vs. 4.29 and 2.6 h at 17 HALO vs. 3.26 and 3.27 at 1 HALO). There were relevant (p<0.05) differences in C_max between the three treated groups for loratadine and desloratadine; 133.05±3.55 and 258.07±14.45 ng/mL at 9 HALO vs. 104.5±2.61 and 188.62±7.20 ng/mL at 1 HALO vs. 94.33±20 and 187.75±10.79 ng/mL at 17 HALO. Drug dosing at 17 HALO resulted in highest loratadine and desloratadine total apparent clearance values: 61.46 and 15.97 L/h/kg, respectively, whereas loratadine and desloratadine clearances (CL) were significantly slower (p<0.05) at the other administration times (loratadine and desloratadine CL was 57.3 and 14.22 L/h/kg at 1 HALO vs. 43.79 and 12.89 L/h/kg at 9 HALO, respectively). The area under the concentration‐time curve (AUC) of loratadine and desloratadine was significantly (p<0.05) greater following drug administration at 9 HALO (456.75 and 1550.57 (ng/mL) · h, respectively); it was lowest following treatment at 17 HALO (325.39 and 1252.53 (ng/mL) · h, respectively). These pharmacokinetic data indicate that the administration time of loratadine significantly affected its pharmacokinetics: the elimination of loratadine and its major metabolite desloratadine.     

Effect of α-p-chlorophenoxyisobutyrate on the metabolism of isoprenoid compounds in the rat

1. Feeding of alpha-p-chlorophenoxyisobutyrate (CPIB) to rats increased ubiquinone concentration in the liver but not in other tissues. The increase was progressive with the time of feeding and related to the concentration of CPIB in the diet. 2. Incorporation of [1-(14)C]acetate, but not of [2-(14)C]mevalonate, into sterols in the liver in vivo or by liver slices in vitro was decreased on feeding the rats with CPIB. However, incorporation of mevalonate into ubiquinone increased. 3. CPIB, when added in low concentrations to liver slices, had no effect on isoprene synthesis from acetate; higher concentrations, however, were inhibitory. 4. No activation of ubiquinone synthesis from mevalonate was observed when CPIB was added to the liver slices synthesizing ubiquinone. 5. The increase in ubiquinone in CPIB-fed animals appears to be due to increased synthesis in the initial stages and to decreased catabolism in the later stages. 6. An inverse relationship was found between the concentration of ubiquinone in the liver and the serum sterol concentration in CPIB-fed rats.     

Labs in the Field? Rocky Mountain Biological Stations in the Early Twentieth Century

Biological field stations proliferated in the Rocky Mountains region of the western United States during the early decades of the twentieth century. This essay examines these Rocky Mountain field stations as hybrid lab-field sites from the perspective of the field side of the dichotomy: as field sites with raised walls rather than as laboratories whose walls with the natural world have been lowered. Not only were these field stations transformed to be more like laboratories, but they were also embedded within the particular regional environmental and institutional context of the Rocky Mountains. Using the University of Colorado's Mountain Laboratory at Tolland and other contemporaneous sites as examples, this essay analyzes key features of these sites, including their location within transportation networks, buildings, equipment, personnel, scheduling, recreational and social activities, and other material and social practices on the ground. Considering both the distinctive and shared characteristics of the Rocky Mountain field stations in comparison to other types of field stations provides a more complete picture of the diversity and range of lab-field hybrid sites in the biological sciences in the early twentieth-century United States.     

Evolution of the Tribosphenic Molar Pattern in Early Mammals,with Comments on the “Dual-Origin” Hypothesis

Development of the tribosphenic molar was a fundamental event that likely influenced the rise of modern mammals. This multi-functional complex combined shearing and grinding in a single chewing stroke, and provided the base morphology for the later evolution of the myriad dental morphologies employed by mammals today. Here a series of morphotypes are presented that represent stepwise acquisition of characters of the molar crown, in an effort to clarify homologies and functional analogies among molars of tribosphenic and tribosphenic-like mammals, as well as their putative sister groups. This is accomplished by evaluation of wear features, which provide direct evidence of occlusal function, and mapping these features on molars of the various morphotypes demonstrates their utility in determining homology. The original singular lower molar talonid cusp is homologous with the hypoconid, and upper molar cusp C in early mammals is homologous with the metacone (cusp “C” is a neomorph with variable occurrence). The lingual translation of the metacone to a position more directly distal to the paracone (as in Peramus) creates an embrasure for the lower molar hypoconid, and is accompanied by the development of the hypoconulid and a new shearing surface. Lastly, the Gondwanan radiation of tribosphenic-like mammals, the Australosphenida (including monotremes), is determined to be functionally non-tribosphenic. The Tribosphenida are restricted to Laurasian taxa, with an origin at or just prior to the Jurassic-Cretaceous boundary.     

The Effect of Cigarette Smoke Exposure on the Development of Inflammation in Lungs,Gut and Joints of TNFΔARE Mice

The inflammatory cytokine TNF-α is a central mediator in many immune-mediated diseases, such as Crohn’s disease (CD), spondyloarthritis (SpA) and chronic obstructive pulmonary disease (COPD). Epidemiologic studies have shown that cigarette smoking (CS) is a prominent common risk factor in these TNF-dependent diseases. We exposed TNF^ΔARE mice; in which a systemic TNF-α overexpression leads to the development of inflammation; to 2 or 4 weeks of air or CS. We investigated the effect of deregulated TNF expression on CS-induced pulmonary inflammation and the effect of CS exposure on the initiation and progression of gut and joint inflammation. Upon 2 weeks of CS exposure, inflammation in lungs of TNF^ΔARE mice was significantly aggravated. However, upon 4 weeks of CS-exposure, this aggravation was no longer observed. TNF^ΔARE mice have no increases in CD4+ and CD8+ T cells and a diminished neutrophil response in the lungs after 4 weeks of CS exposure. In the gut and joints of TNF^ΔARE mice, 2 or 4 weeks of CS exposure did not modulate the development of inflammation. In conclusion, CS exposure does not modulate gut and joint inflammation in TNF^ΔARE mice. The lung responses towards CS in TNF^ΔARE mice however depend on the duration of CS exposure.     

Effect of Antihypertensive Drugs on the “Intrinsic” Heart Rate

“Intrinsic” heart rate in man was measured by giving simultaneous atropine and propranolol and used to study the direct effect of antihypertensive drugs on the heart. Though the intrinsic and control heart rates decreased significantly following the administration of reserpine, there was no significant difference between high and low doses. No similar effects were observed with debrisoquine sulphate and methyldopa, though in high doses the latter produced a decrease which was of some statistical significance.     

Effect of “Chemical” Hypoxia on the Potassium Conductance of the Membrane of Pheochromocytoma Cells

We studied the effect of “chemical” (induced by the action of sodium thiosulfate, STS) hypoxia on the potassium conductance of the membrane of pheochromocytoma cells. Application of 1 to 10 mM STS decreased in a dose-dependent manner the amplitude of integral potassium current without changes in the voltage dependence of its activation. The concentration dependence of the action of STS on the amplitude of potassium current was estimated using the Boltzmann equation. The value of concentration for 50% inhibition was 2.7 ± 0.2 mM, while the slope coefficient was 0.9 ± 0.2 mM⁻¹. In the presence of 10 mM STS, the decrease in the amplitude of potassium current reached, on average, 55%. Therefore, “chemical” hypoxia influences rather significantly the potassium conductance of the membrane of pheochromocytoma PC12 cells.     

Effect of PLCβ4 in the thalamus on the EEG in REM sleep

Sleep and Biological Rhythms -     

Effect of anticancer drugs on the release of interferon γ in vitro

Summary Some conventional and experimental anticancer drugs were tested for their effect on concanavalin-A-induced interferon release from rat splenocytes in vitro. When 2.5 × 10⁶ rat splenocytes/ml, stimulated with 1 µg/ml concanavalin A, were incubated with various non-cytotoxic doses of the vinca alkaloid vincristine, there was an inhibition of the release of interferon in culture supernatants. The antitumour antibiotics bleomycin and Adriamycin, alkylating agents 4-hydroperoxycyclophosphamide and mafosfamide, and the immunoactive peptides FK 156 and FK565 did not affect the release of interferon under similar conditions. However, cyclosporin A, in similar experiments, markedly inhibited the release of interferon .     

Antinociceptive Effect of Tetrandrine on LPS-Induced Hyperalgesia via the Inhibition of IKKβ Phosphorylation and the COX-2/PGE2 Pathway in Mice

Tetrandrine (TET) is a bisbenzylisoquinoline alkaloid that is isolated from the Stephania Tetrandra. It is known to possess anti-inflammatory and immunomodulatory effects. We have shown that TET can effectively suppress the production of bacterial lipopolysaccharide (LPS)-induced inflammatory mediators, including cyclooxygenases (COXs), in macrophages. However, whether TET has an antinociceptive effect on LPS-induced hyperalgesia is unknown. In the present study, we investigated the potential antinociceptive effects of TET and the mechanisms by which it elicits its effects on LPS-induced hyperalgesia. LPS effectively evoked hyperalgesia and induced the production of PGE₂ in the sera, brain tissues, and cultured astroglia. TET pretreatment attenuated all of these effects. LPS also activated inhibitor of κB (IκB) kinase β (IKKβ) and its downstream components in the IκB/nuclear factor (NF)-κB signaling pathway, including COX-2; the increase in expression levels of these components was significantly abolished by TET. Furthermore, in primary astroglia, knockdown of IKKβ, but not IKKα, reversed the effects of TET on the LPS-induced increase in IκB phosphorylation, P65 phosphorylation, and COX-2. Our results suggest that TET can effectively exert antinociceptive effects on LPS-induced hyperalgesia in mice by inhibiting IKKβ phosphorylation, which leads to the reduction in the production of important pain mediators, such as PGE₂ and COX-2, via the IKKβ/IκB/NF-κB pathway.     

Involvement of Inducible 6-Phosphofructo-2-kinase in the Anti-diabetic Effect of Peroxisome Proliferator-activated Receptor γ Activation in Mice

PFKFB3 is the gene that codes for the inducible isoform of 6-phosphofructo-2-kinase (iPFK2), a key regulatory enzyme of glycolysis. As one of the targets of peroxisome proliferator-activated receptor γ (PPARγ), PFKFB3/iPFK2 is up-regulated by thiazolidinediones. In the present study, using PFKFB3/iPFK2-disrupted mice, the role of PFKFB3/iPFK2 in the anti-diabetic effect of PPARγ activation was determined. In wild-type littermate mice, PPARγ activation (i.e. treatment with rosiglitazone) restored euglycemia and reversed high fat diet-induced insulin resistance and glucose intolerance. In contrast, PPARγ activation did not reduce high fat diet-induced hyperglycemia and failed to reverse insulin resistance and glucose intolerance in PFKFB3^+/− mice. The lack of anti-diabetic effect in PFKFB3^+/− mice was associated with the inability of PPARγ activation to suppress adipose tissue lipolysis and proinflammatory cytokine production, stimulate visceral fat accumulation, enhance adipose tissue insulin signaling, and appropriately regulate adipokine expression. Similarly, in cultured 3T3-L1 adipocytes, knockdown of PFKFB3/iPFK2 lessened the effect of PPARγ activation on stimulating lipid accumulation. Furthermore, PPARγ activation did not suppress inflammatory signaling in PFKFB3/iPFK2-knockdown adipocytes as it did in control adipocytes. Upon inhibition of excessive fatty acid oxidation in PFKFB3/iPFK2-knockdown adipocytes, PPARγ activation was able to significantly reverse inflammatory signaling and proinflammatory cytokine expression and restore insulin signaling. Together, these data demonstrate that PFKFB3/iPFK2 is critically involved in the anti-diabetic effect of PPARγ activation.     

Effect of Low-Frequency Pulsed Magnetic Field and Low-Level Laser Radiation on Oxidoreductase Activity and Growth of Fungi—Active Destructors of Polymer Materials

Microbiology - Effect of low-frequency pulsed magnetic field and of low-intensity laser radiation on mycelial fungi actively degrading various polymer materials was studied. These factors had a...