Access and distribution of exogenous substances in the intercellular clefts of the rat adenohypophysis

: As a kind of haemoglobin, cytochrome P450 enzymes (CYP450) participate in the metabolism of many substances, including endogenous substances, exogenous substances and drugs. It is estimated that 60% of common prescription drugs require bioconversion through CYP450. The influence of macrolides on CYP450 contributes to the metabolism and drug-drug interactions (DDIs) of macrolides. At present, most studies on the effects of macrolides on CYP450 are focused on CYP3A, but a few exist on other enzymes and drug combinations, such as telithromycin, which can decrease the activity of hepatic CYP1A2 and CYP3A2. This article summarizes some published applications of the influence of macrolides on CYP450 and the DDIs of macrolides caused by CYP450. And the article may subsequently guide the rational use of drugs in clinical trials. To a certain extent, poisoning caused by adverse drug interactions can be avoided. Unreasonable use of macrolide antibiotics may enable the presence of residue of macrolide antibiotics in animal-origin food. It is unhealthy for people to eat food with macrolide antibiotic residues. So it is of great significance to guarantee food safety and protect the health of consumers by the rational use of macrolides. This review gives a detailed description of the influence of macrolides on CYP450 and the DDIs of macrolides caused by CYP450. Moreover, it offers a perspective for researchers to further explore in this area.

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Factors affecting hallucinations in patients with delirium

Scientific Reports ◽

10.1038/s41598-021-92578-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Masako Tachibana ◽

Toshiya Inada ◽

Masaru Ichida ◽

Norio Ozaki

Keyword(s):

Rating Scale ◽

Detailed Examination ◽

Individual Factors ◽

Visual Hallucinations ◽

Angiotensin Ii Receptor ◽

Contributing Factors ◽

Factors Affecting ◽

Receptor Blockers ◽

Benzodiazepine Withdrawal ◽

Exogenous Substances

AbstractDelirium develops through a multifactorial process and include multiple subtypes with different pathological factors. To refine the treatment and care for delirium, a more detailed examination of these subtypes is needed. Therefore, this study aimed to explore the factors affecting delirium in cases in which hallucinations are conspicuous. In total, 602 delirium cases referred to the psychiatry department at a general hospital between May 2015 and August 2020 were enrolled. The Delirium Rating Scale-revised-98 was used to assess perceptual disturbances and hallucinations in patients with delirium. Multiple regression analysis was applied to determine whether individual factors were associated with the hallucinations. A total of 156 patients with delirium (25.9%) experienced hallucinations, with visual hallucinations being the most common subtype. Alcohol drinking (p < 0.0005), benzodiazepine withdrawal (p = 0.004), and the use of angiotensin II receptor blockers (p = 0.007) or dopamine receptor agonists (p = 0.014) were found to be significantly associated with hallucinations in patients with delirium. The four factors detected in this study could all be reversible contributing factors derived from the use of or withdrawal from exogenous substances.

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Nucleotide-Binding Leucine-Rich Repeat Genes CsRSF1 and CsRSF2 Are Positive Modulators in the Cucumis sativus Defense Response to Sphaerotheca fuliginea

International Journal of Molecular Sciences ◽

10.3390/ijms22083986 ◽

2021 ◽

Vol 22 (8) ◽

pp. 3986

Author(s):

Xue Wang ◽

Qiumin Chen ◽

Jingnan Huang ◽

Xiangnan Meng ◽

Na Cui ◽

...

Keyword(s):

Cell Membrane ◽

Defense Response ◽

Nucleotide Binding ◽

Plant Defense Response ◽

Sphaerotheca Fuliginea ◽

Leucine Rich Repeat ◽

Transcript Levels ◽

Yield And Quality ◽

Leucine Rich Repeats ◽

Exogenous Substances

Cucumber powdery mildew caused by Sphaerotheca fuliginea is a leaf disease that seriously affects cucumber’s yield and quality. This study aimed to report two nucleotide-binding site-leucine-rich repeats (NBS-LRR) genes CsRSF1 and CsRSF2, which participated in regulating the resistance of cucumber to S. fuliginea. The subcellular localization showed that the CsRSF1 protein was localized in the nucleus, cytoplasm, and cell membrane, while the CsRSF2 protein was localized in the cell membrane and cytoplasm. In addition, the transcript levels of CsRSF1 and CsRSF2 were different between resistant and susceptible cultivars after treatment with exogenous substances, such as abscisic acid (ABA), methyl jasmonate (MeJA), salicylic acid (SA), ethephon (ETH), gibberellin (GA) and hydrogen peroxide (H2O2). The expression analysis showed that the transcript levels of CsRSF1 and CsRSF2 were correlated with plant defense response against S. fuliginea. Moreover, the silencing of CsRSF1 and CsRSF2 impaired host resistance to S. fuliginea, but CsRSF1 and CsRSF2 overexpression improved resistance to S. fuliginea in cucumber. These results showed that CsRSF1 and CsRSF2 genes positively contributed to the resistance of cucumber to S. fuliginea. At the same time, CsRSF1 and CsRSF2 genes could also regulate the expression of defense-related genes. The findings of this study might help enhance the resistance of cucumber to S. fuliginea.

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Acquisition of Adaptive Traits via Interspecific Association: Ecological Consequences and Applications

Ecologies ◽

10.3390/ecologies2010004 ◽

2021 ◽

Vol 2 (1) ◽

pp. 43-70

Author(s):

Aabir Banerji

Keyword(s):

Natural Selection ◽

Gene Transfer ◽

Horizontal Gene Transfer ◽

Natural Resource Management ◽

Natural Resource ◽

Environmental Cues ◽

Ecological Interactions ◽

Interspecific Association ◽

Adaptive Traits ◽

Exogenous Substances

Adaptative traits enable organisms to survive and reproduce. Though these traits are often innate features (ones that may or may not exhibit variability in response to environmental cues or originate from horizontal gene transfer), this is not always the case. Many species endure natural selection not with the traits they possess intrinsically but with exogenous substances and abilities that they acquire from other species, via ecological interactions akin to outsourcing, pillaging, and fraud. Here, I review the mechanisms of this exogenous trait acquisition and highlight some of their repercussions and usefulness for natural resource management, industry, and human health.

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Validation of Recombinant Chicken Liver Bile Acid Binding Protein as a Tool for Cholic Acid Hosting

Biomolecules ◽

10.3390/biom11050645 ◽

2021 ◽

Vol 11 (5) ◽

pp. 645

Author(s):

Giusy Tassone ◽

Maurizio Orlandini ◽

Massimo Olivucci ◽

Cecilia Pozzi

Keyword(s):

Bile Acid ◽

High Resolution ◽

Affinity Chromatography ◽

Bile Acids ◽

Drug Carriers ◽

Chicken Liver ◽

Purification Procedure ◽

Acid Binding Protein ◽

Bile Acid Binding ◽

Exogenous Substances

Bile acids (BAs) are hydroxylated steroids derived from cholesterol that act at the intestinal level to facilitate the absorption of several nutrients and also play a role as signaling molecules. In the liver of various vertebrates, the trafficking of BAs is mediated by bile acid-binding proteins (L-BABPs). The ability to host hydrophobic or amphipathic molecules makes BABPs suitable for the distribution of a variety of physiological and exogenous substances. Thus, BABPs have been proposed as drug carriers, and more recently, they have also been employed to develop innovative nanotechnology and biotechnology systems. Here, we report an efficient protocol for the production, purification, and crystallization of chicken liver BABP (cL-BABP). By means of target expression as His6-tag cL-BABP, we obtained a large amount of pure and homogeneous proteins through a simple purification procedure relying on affinity chromatography. The recombinant cL-BABP showed a raised propensity to crystallize, allowing us to obtain its structure at high resolution and, in turn, assess the structural conservation of the recombinant cL-BABP with respect to the liver-extracted protein. The results support the use of recombinant cL-BABP for the development of drug carriers, nanotechnologies, and innovative synthetic photoswitch systems.

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A Comprehensive Spectroscopic Analysis of the Ibuprofen Binding with Human Serum Albumin, Part II

Scientia Pharmaceutica ◽

10.3390/scipharm89030030 ◽

2021 ◽

Vol 89 (3) ◽

pp. 30

Author(s):

Anna Ploch-Jankowska ◽

Danuta Pentak ◽

Jacek E. Nycz

Keyword(s):

Fatty Acids ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Tertiary Structure ◽

Temperature Characteristic ◽

The Body ◽

Structural Modifications ◽

Influence Of Temperature On ◽

Exogenous Substances

Human serum albumin (HSA) is the most abundant human plasma protein. HSA plays a crucial role in many binding endos- and exogenous substances, which affects their pharmacological effect. The innovative aspect of the study is not only the interaction of fatted (HSA) and defatted (dHSA) human serum albumin with ibuprofen (IBU), but the analysis of the influence of temperature on the structural modifications of albumin and the interaction between the drug and proteins from the temperature characteristic of near hypothermia (308 K) to the temperature reflecting inflammation in the body (312 K and 314 K). Ibuprofen is a non-steroidal anti-inflammatory drug. IBU is used to relieve acute pain, inflammation, and fever. To determine ibuprofen’s binding site in the tertiary structure of HSA and dHSA, fluorescence spectroscopy was used. On its basis, the fluorescent emissive spectra of albumin (5 × 10−6 mol/dm3) without and with the presence of ibuprofen (1 × 10−5–1 × 10−4 mol/dm3) was recorded. The IBU-HSA complex’s fluorescence was excited by radiation of wavelengths of λex 275 nm and λex 295 nm. Spectrophotometric spectroscopy allowed for recording the absorbance spectra (zero-order and second derivative absorption spectra) of HSA and dHSA under the influence of ibuprofen (1 × 10−4 mol/dm3). To characterize the changes of albumin structure the presence of IBU, circular dichroism was used. The data obtained show that the presence of fatty acids and human serum albumin temperature influences the strength and type of interaction between serum albumin and drug. Ibuprofen binds more strongly to defatted human serum albumin than to albumin in the presence of fatty acids. Additionally, stronger complexes are formed with increasing temperatures. The competitive binding of ibuprofen and fatty acids to albumin may influence the concentration of free drug fraction and thus its therapeutic effect.

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Accessibility of the Central Nervous Connectives of Anodonta Cygnea to a Compound of Large Molecular Weight

Journal of Experimental Biology ◽

10.1242/jeb.56.2.493 ◽

1972 ◽

Vol 56 (2) ◽

pp. 493-499

Author(s):

N. J. LANE ◽

J. E. TREHERNE

Keyword(s):

Cell Layer ◽

Extracellular Fluid ◽

Water Soluble ◽

Bathing Medium ◽

Anodonta Cygnea ◽

Rapid Exchange ◽

Soluble Ions ◽

Large Molecular Weight ◽

Water Soluble Ions ◽

Intercellular Clefts

1. Ultrastructural observations on the uptake of an exogenous tracer substance, horseradish peroxidase (M.W. 40,000), have shown that this large molecule can penetrate the neural lamella in intact cerebro-visceral connectives of the lamellibranch, Anodonta cygnea. 2. Peroxidase molecules were also observed to penetrate between the intercellular clefts formed by adjacent membranes of the underlying peripheral glial cell layer and to move extensively into the underlying extracellular spaces. 3. These observations confirm the results of previous electrophysiological, radioisotopic and ultrastructural investigations indicating that a relatively rapid exchange of water-soluble ions and molecules occurs between the blood, or bathing medium, and the extracellular fluid bathing the axon surfaces in intact connectives.

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Insect peripheral nerves: accessibility of neurohaemal regions to lanthanum

Journal of Cell Science ◽

10.1242/jcs.18.1.179 ◽

1975 ◽

Vol 18 (1) ◽

pp. 179-197 ◽

Cited By ~ 3

Author(s):

N.J. Lane ◽

R.A. Leslie ◽

L.S. Swales

Keyword(s):

Blood Brain Barrier ◽

Peripheral Nerves ◽

Rhodnius Prolixus ◽

Ionic Lanthanum ◽

Neurosecretory Axon ◽

Thin Part ◽

Free Media ◽

Exogenous Substances

During incubation in vivo, exogenously applied ionic lanthanum comes to surround the numerous neurosecretory terminals which are found lying within or immediately beneath the acellular neural lamella ensheathing the nerves from fifth instar and adult specimens of Rhodnius prolixus. The lanthanum does not penetrate beyond the cellular perineurium, which completely surrounds the non-neurosecretory axons in these nerves and constitutes a form of ‘blood-brain barrier’. In some cases, however, lanthanum is found in the vicinity of a neurosecretory axon lying beneath the perineurium, where it can be assumed to have leaked in from the neurosecretory terminal lying free in the neural lamella. When nerves are incubated in calcium-free media, regions with an attenuated perineurium become ‘leaky’, in that lanthanum is found lying in those extracellular spaces between axons and glia which lie immediately below the thin part of the perineurial layer. Bathing solutions made slightly hyperosmotic to the haemolymph with sucrose have no apparent disruptive effects on the barrier. When the tissues are incubated in more hypertonic solutions, the perineurial barrier becomes ‘leaky’ throughout, and tracer pervades beyond its cells into all the intercellular spaced between glia and axons. The possible role of the zonulae occludentes in both the maintenance of the perineurial barrier and in the formation of interglial occlusions to local penetration of exogenous substances is considered.

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The permeability properties of septate junctions in Malpighian tubules of Rhodnius

Journal of Cell Science ◽

10.1242/jcs.88.2.251 ◽

1987 ◽

Vol 88 (2) ◽

pp. 251-265 ◽

Cited By ~ 1

Author(s):

H.B. Skaer ◽

S.H. Maddrell ◽

J.B. Harrison

Keyword(s):

Structural Characteristics ◽

Malpighian Tubule ◽

Malpighian Tubules ◽

Septate Junctions ◽

Blood Sucking ◽

Effects Of Ph ◽

Intercellular Clefts ◽

Luminal Flow ◽

Tubule Cells ◽

Positively Charged

This paper describes the structural characteristics and permeability properties of the smooth septate junctions between the upper Malpighian tubule cells of a blood-sucking bug, Rhodnius prolixus. The permeability of the paracellular route was tested only for solutes that could be demonstrated not to cross the epithelium via the cellular route. The intercellular clefts were readily permeated by sucrose, inulin and polyethylene glycol (PEG), showing a higher permeability to molecules of smaller radius (PEG versus sucrose). Negatively charged molecules permeated the clefts more readily than positively charged ones. The effects of pH, urea and luminal flow rate on permeability were studied. The results are discussed in relation to the physiological tightness of the Malpighian tubules to certain solutes and to its function as an excretory epithelium.

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