The Passive Permeability of Insect Malpighian Tubules to Organic Solutes

1974 ◽  
Vol 60 (3) ◽  
pp. 641-652
Author(s):  
S. H. P. MADDRELL ◽  
B. O. C. GARDINER
Keyword(s):  
Small Molecules ◽  
Malpighian Tubules ◽  
Organic Solutes ◽  
In Vitro Experiments ◽  
High Permeability ◽  
Rapid Loss ◽  
Passive Permeability ◽  
Bathing Fluid

1. The permeability of Malpighian tubules of five insect species to a range of organic solutes has been measured by both in vitro and in vivo techniques. 2. Nearly all the substances tested were found, in in vitro experiments, to penetrate the walls of Malpighian tubules in a manner which, on several criteria, was judged to be passive. 3. The walls of Malpighian tubules are more permeable to small molecules than to large ones; but even inulin (MW 5200) penetrates fast enough to reach concentrations which, in tubules secreting fluid slowly, can be as high in the secreted fluid as 50% of its concentration in the bathing fluid. 4. Inulin injected into Schistocerca and L-fucose injected into Rhodnius appeared in the excreta at rates which could be accurately predicted from the in vitro behaviour of Malpighian tubules of these insects. 5. Taken with the fact that the cuticular lining of the rectum of insects is thought to be not very permeable, the high permeability of insect Malpighian tubules means that the reabsorption of useful compounds of the order of size of disaccharides must to some extent occur before excretory material reaches the rectum. 6. It is suggested that the circulation of lipids and hormones in the form of complexes with proteins is a device to prevent their rapid loss through the excretory system.

scholarly journals Excretion of NaCl and KCl loads in mosquitoes. 2. Effects of the small molecule Kir channel modulator VU573 and its inactive analog VU342

2014 ◽  
Vol 307 (7) ◽  
pp. R850-R861 ◽  
Author(s):  
Matthew F. Rouhier ◽  
Rebecca M. Hine ◽  
Seokhwan Terry Park ◽  
Rene Raphemot ◽  
Jerod Denton ◽  
...  
Keyword(s):  
Urinary Excretion ◽  
Small Molecules ◽  
Fluid Secretion ◽  
Ringer Solution ◽  
Malpighian Tubules ◽  
Kir Channel ◽  
Channel Modulator ◽  
Inactive Analog

The effect of two small molecules VU342 and VU573 on renal functions in the yellow fever mosquito Aedes aegypti was investigated in vitro and in vivo. In isolated Malpighian tubules, VU342 (10 μM) had no effect on the transepithelial secretion of Na+, K+, Cl−, and water. In contrast, 10 μM VU573 first stimulated and then inhibited the transepithelial secretion of fluid when the tubules were bathed in Na+-rich or K+-rich Ringer solution. The early stimulation was blocked by bumetanide, suggesting the transient stimulation of Na-K-2Cl cotransport, and the late inhibition of fluid secretion was consistent with the known block of AeKir1, an Aedes inward rectifier K+ channel, by VU573. VU342 and VU573 at a hemolymph concentration of about 11 μM had no effect on the diuresis triggered by hemolymph Na+ or K+ loads. VU342 at a hemolymph concentration of 420 μM had no effect on the diuresis elicited by hemolymph Na+ or K+ loads. In contrast, the same concentration of VU573 significantly diminished the Na+ diuresis by inhibiting the urinary excretion of Na+, Cl−, and water. In K+-loaded mosquitoes, 420 μM VU573 significantly diminished the K+ diuresis by inhibiting the urinary excretion of K+, Na+, Cl−, and water. We conclude that 1) the effects of VU573 observed in isolated Malpighian tubules are overwhelmed in vivo by the diuresis triggered with the coinjection of Na+ and K+ loads, and 2) at a hemolymph concentration of 420 μM VU573 affects Kir channels systemically, including those that might be involved in the release of diuretic hormones.

scholarly journals The In Vivo and In Vitro Toxicokinetics of Citreoviridin Extracted from Penicillium citreonigrum

Toxins ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 360 ◽  
Author(s):  
Yosuke Uchiyama ◽  
Masahiko Takino ◽  
Michiko Noguchi ◽  
Nozomi Shiratori ◽  
Naoki Kobayashi ◽  
...  
Keyword(s):  
Permeability Coefficient ◽  
The Body ◽  
In Vitro Experiments ◽  
High Permeability ◽  
In Vivo Experiments ◽  
Permeability Study ◽  
High Bioavailability ◽  
S9 Fraction

Citreoviridin (CTVD), a mycotoxin called yellow rice toxin, is reported to be related to acute cardiac beriberi; however, its toxicokinetics remain unclear. The present study elucidated the toxicokinetics through in vivo experiments in swine and predicted the human toxicokinetics by comparing the findings to those from in vitro experiments. In vivo experiments revealed the high bioavailability of CTVD (116.4%) in swine. An intestinal permeability study using Caco-2 cells to estimate the toxicokinetics in humans showed that CTVD has a high permeability coefficient. When CTVD was incubated with hepatic S9 fraction from swine and humans, hydroxylation and methylation, desaturation, and dihydroxylation derivatives were produced as the predominant metabolites. The levels of these products produced using human S9 were higher than those obtained swine S9, while CTVD glucuronide was produced slowly in human S9 in comparison to swine S9. Furthermore, the elimination of CTVD by human S9 was significantly more rapid in comparison to that by swine S9. These results suggest that CTVD is easily absorbed in swine and that it remains in the body where it is slowly metabolized. In contrast, the absorption of CTVD in humans would be the same as that in swine, although its elimination would be faster.

scholarly journals Analysis of the size dependence of macromolecular crowding shows that smaller is better

2015 ◽  
Vol 112 (26) ◽  
pp. 7990-7995 ◽  
Author(s):  
Kim A. Sharp
Keyword(s):  
Small Molecules ◽  
Size Dependence ◽  
Reaction Rates ◽  
Medium Size ◽  
In Vitro Experiments ◽  
High Concentration ◽  
Concentration Effects ◽  
Large Molecules

The aqueous milieu inside cells contains as much as 30–40% dissolved protein and RNA by volume. This large concentration of macromolecules is expected to cause significant deviations from solution ideality. In vivo biochemical reaction rates and equilibria might differ significantly from those measured in the majority of in vitro experiments that are performed at much lower macromolecule concentrations. Consequently crowding, a nonspecific phenomenon believed to arise from the large excluded volume of these macromolecules, has been studied extensively by experimental and theoretical methods. However, the relevant theory has not been applied consistently. When the steric effects of macromolecular crowders and small molecules like water and ions are treated on an equal footing, the effect of the macromolecules is opposite to that commonly believed. Large molecules are less effective at crowding than water and ions. There is also a surprisingly weak dependence on crowder size. Molecules of medium size, ∼5 Å radius, have the same effect as much larger macromolecules like proteins and RNA. These results require a reassessment of observed high-concentration effects and of strategies to mimic in vivo conditions with in vitro experiments.

Conjugates of Classical DNA/RNA Binder with Nucleobase: Chemical, Biochemical and Biomedical Applications

2019 ◽  
Vol 26 (30) ◽  
pp. 5609-5624
Author(s):  
Dijana Saftić ◽  
Željka Ban ◽  
Josipa Matić ◽  
Lidija-Marija Tumirv ◽  
Ivo Piantanida
Keyword(s):  
Molecular Weight ◽  
Small Molecules ◽  
Biomedical Applications ◽  
Protein Targets ◽  
New Class ◽  
Rna Targets ◽  
Covalently Linked ◽  
Structural Aspects

: Among the most intensively studied classes of small molecules (molecular weight < 650) in biomedical research are small molecules that non-covalently bind to DNA/RNA, and another intensively studied class is nucleobase derivatives. Both classes have been intensively elaborated in many books and reviews. However, conjugates consisting of DNA/RNA binder covalently linked to nucleobase are much less studied and have not been reviewed in the last two decades. Therefore, this review summarized reports on the design of classical DNA/RNA binder – nucleobase conjugates, as well as data about their interactions with various DNA or RNA targets, and even in some cases protein targets are involved. According to these data, the most important structural aspects of selective or even specific recognition between small molecule and target are proposed, and where possible related biochemical and biomedical aspects were discussed. The general conclusion is that this, rather new class of molecules showed an amazing set of recognition tools for numerous DNA or RNA targets in the last two decades, as well as few intriguing in vitro and in vivo selectivities. Several lead research lines show promising advancements toward either novel, highly selective markers or bioactive, potentially druggable molecules.

scholarly journals Development of a gel dedicated to gel immersion endoscopy

2021 ◽  
Vol 09 (06) ◽  
pp. E918-E924
Author(s):  
Tomonori Yano ◽  
Atsushi Ohata ◽  
Yuji Hiraki ◽  
Makoto Tanaka ◽  
Satoshi Shinozaki ◽  
...  
Keyword(s):  
Electrical Conductivity ◽  
Porcine Model ◽  
Ex Vivo ◽  
In Vitro Experiments ◽  
Efficacy And Safety ◽  
Coagulative Necrosis ◽  
Novel Technique ◽  
In Vivo Experiments

Abstract Backgrounds and study aims Gel immersion endoscopy is a novel technique to secure the visual field during endoscopy. The aim of this study was to develop a dedicated gel for this technique. Methods To identify appropriate viscoelasticity and electrical conductivity, various gels were examined. Based on these results, the dedicated gel “OPF-203” was developed. Efficacy and safety of OPF-203 were evaluated in a porcine model. Results  In vitro experiments showed that a viscosity of 230 to 1900 mPa·s, loss tangent (tanδ) ≤ 0.6, and hardness of 240 to 540 N/cm2 were suitable. Ex vivo experiments showed electrical conductivity ≤ 220 μS/cm is appropriate. In vivo experiments using gastrointestinal bleeding showed that OPF-203 provided clear visualization compared to water. After electrocoagulation of gastric mucosa in OPF-203, severe coagulative necrosis was not observed in the muscularis but limited to the mucosa. Conclusions OPF-203 is useful for gel immersion endoscopy.

Computational study for suppression of CD25/IL-2 interaction

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Moein Dehbashi ◽  
Zohreh Hojati ◽  
Majid Motovali-bashi ◽  
Mazdak Ganjalikhani-Hakemi ◽  
Akihiro Shimosaka ◽  
...  
Keyword(s):  
Small Molecules ◽  
Cancer Progression ◽  
Immune Escape ◽  
De Novo ◽  
Computational Study ◽  
Treg Cells ◽  
Homology Search ◽  
Small Interfering Rnas

AbstractCancer recurrence presents a huge challenge in cancer patient management. Immune escape is a key mechanism of cancer progression and metastatic dissemination. CD25 is expressed in regulatory T (Treg) cells including tumor-infiltrating Treg cells (TI-Tregs). These cells specially activate and reinforce immune escape mechanism of cancers. The suppression of CD25/IL-2 interaction would be useful against Treg cells activation and ultimately immune escape of cancer. Here, software, web servers and databases were used, at which in silico designed small interfering RNAs (siRNAs), de novo designed peptides and virtual screened small molecules against CD25 were introduced for the prospect of eliminating cancer immune escape and obtaining successful treatment. We obtained siRNAs with low off-target effects. Further, small molecules based on the binding homology search in ligand and receptor similarity were introduced. Finally, the critical amino acids on CD25 were targeted by a de novo designed peptide with disulfide bond. Hence we introduced computational-based antagonists to lay a foundation for further in vitro and in vivo studies.

scholarly journals Study on Establishing Reference Safe Concentrations of MRI Contrast Agents for Optimized Images: Paramagnetic Gd-DTPA-BMEA and Superparamagnetic Ferucarbotran

2021 ◽  
Vol 11 (3) ◽  
pp. 1165
Author(s):  
Wen-Tien Hsiao ◽  
Yi-Hong Chou ◽  
Jhong-Wei Tu ◽  
Ai-Yih Wang ◽  
Lu-Han Lai
Keyword(s):  
Contrast Agent ◽  
Contrast Agents ◽  
Mri Contrast Agents ◽  
Mri Contrast Agent ◽  
In Vitro Experiments ◽  
Mri Contrast ◽  
In Vivo Experiments ◽  
Contrast Agent Injection

The purpose of this study is to establish the minimal injection doses of magnetic resonance imaging (MRI) contrast agents that can achieve optimized images while improving the safety of injectable MRI drugs. Gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) and ferucarbotran, commonly used in clinical practice, were selected and evaluated with in vitro and in vivo experiments. MRI was acquired using T1-weighted (T1W) and T2-weighted (T2W) sequences, and the results were quantitatively analyzed. For in vitro experiments, results showed that T1W and T2W images were optimal when Gd-DTPA-bisamide (2-oxoethyl) (Gd-DTPA-BMEA) and ferucarbotran were diluted to a volume percentage of 0.6% and 0.05%; all comparisons were significant differences in grayscale statistics using one-way analysis of variance (ANOVA). For in vivo experiments, the contrast agent with optimal concentration percentages determined from in vitro experiments were injected into mice with an injection volume of 100 μL, and the images of brain, heart, liver, and mesentery before and after injection were compared. The statistical results showed that the p values of both T1W and T2W were less than 0.001, which were statistically significant. Under safety considerations for MRI contrast agent injection, optimized MRI images could still be obtained after reducing the injection concentration, which can provide a reference for the safety concentrations of MRI contrast agent injection in the future.

Anticancer effect of arsenic trioxide on cholangiocarcinoma: in vitro experiments and in vivo xenograft mouse model

2013 ◽  
Vol 14 (2) ◽  
pp. 215-224 ◽  
Author(s):  
Eun-Young Kim ◽  
Sang Soo Lee ◽  
Ji Hoon Shin ◽  
Soo Hyun Kim ◽  
Dong-Ho Shin ◽  
...  
Keyword(s):  
Mouse Model ◽  
Arsenic Trioxide ◽  
In Vitro Experiments ◽  
Anticancer Effect ◽  
Xenograft Mouse Model

scholarly journals Peptide-tags for site-specific protein labelling in vitro and in vivo

2016 ◽  
Vol 12 (6) ◽  
pp. 1731-1745 ◽  
Author(s):  
Jonathan Lotze ◽  
Ulrike Reinhardt ◽  
Oliver Seitz ◽  
Annette G. Beck-Sickinger
Keyword(s):  
Metal Ions ◽  
Small Molecules ◽  
Protein Localization ◽  
Specific Protein ◽  
Site Specific ◽  
Protein Labelling ◽  
Peptide Interactions ◽  
Peptide Tags

Peptide-tag based labelling can be achieved by (i) enzymes (ii) recognition of metal ions or small molecules and (iii) peptide–peptide interactions and enables site-specific protein visualization to investigate protein localization and trafficking.

The anterior and posterior ‘stomach’ regions of larval Aedes aegypti midgut: regional specialization of ion transport and stimulation by 5-hydroxytryptamine

1999 ◽  
Vol 202 (3) ◽  
pp. 247-252 ◽  
Author(s):  
T.M. Clark ◽  
A. Koch ◽  
D.F. Moffett
Keyword(s):  
Steady State ◽  
Aedes Aegypti ◽  
Ion Transport ◽  
Malpighian Tubules ◽  
Transport Mechanisms ◽  
Regional Specialization ◽  
Negative Deflection ◽  
Electrical Polarity

The ‘stomach’ region of the larval mosquito midgut is divided into histologically distinct anterior and posterior regions. Anterior stomach perfused symmetrically with saline in vitro had an initial transepithelial potential (TEP) of −66 mV (lumen negative) that decayed within 10–15 min to a steady-state TEP near −10 mV that was maintained for at least 1 h. Lumen-positive TEPs were never observed in the anterior stomach. The initial TEP of the perfused posterior stomach was opposite in polarity, but similar in magnitude, to that of the anterior stomach, measuring +75 mV (lumen positive). This initial TEP of the posterior stomach decayed rapidly at first, then more slowly, eventually reversing the electrical polarity of the epithelium as lumen-negative TEPs were recorded in all preparations within 70 min. Nanomolar concentrations of the biogenic amine 5-hydroxytryptamine (5-HT, serotonin) stimulated both regions, causing a negative deflection of the TEP of the anterior stomach and a positive deflection of the TEP of the posterior stomach. Phorbol 12,13-diacetate also caused a negative deflection of the TEP of the anterior stomach, but had no effect on the TEP of the posterior stomach. These data demonstrate that 5-HT stimulates region-specific ion-transport mechanisms in the stomach of Aedes aegypti and suggest that 5-HT coordinates the actions of the Malpighian tubules and midgut in the maintenance of an appropriate hemolymph composition in vivo.

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