In situ method to estimate local effect of nasal preparations

The potential local toxicity to the respiratory mucosa of drugs, excipients and formulations should be tested in an appropriate animal model. Today: many models are available for such studies, giving different information. Since the mucociliary clearance is one of the most important defence mechanism of the human body against inhaled dust, allergens and microorganisms this mechanism may not be alTected or destroyed. Environmental conditions, such as humidity, temperature,airborne toxins, as well as chemicals and many pharmaceutical excipients affects this mechanism. This review gives a short insight into this field, focusing mainly on the frog palate model, Where the effect of drugs on the mueoeiliary transport rate may be studied

A simple flow-injection method for the determination of blood glucose using a Technicon immobilized enzyme coil

The applicability of a single-channel flow-injection system with immobilized enzyme coil (Technicon) and UV detection to the determination of glucose is described. The method was used for a pure glucose solution and for serum. The detection limit was 0.10 mM, the rate of determination was 20-40 per hour and the precision was satisfactory. The system is very simple and practical when many analysis are to be determined periodically

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Two Intranasal Administration Techniques Give Two Different Pharmacokinetic Results

Minor changes in the administration technique used for intranasal instillation of clonazepam, have been  found to influence the results significantly. A simple study was performed, where rabbits received 0.5 mg  clonazepam intranasally. One group received the drug while fixed in a sitting position, where the other  group was fixed in a supine position. The results show that both techniques where able to provide a rapid  absorption with a tmax around 3-4 min. The Cmax and AUC, however, were very different. The Cmax was found  to be 40 ng/ml and 86 ng/ml, respectively, and the AUC was found to be 891 and 2249 (ng/ml/min), respectively,  for the sitting and the supine position. The relative bioavailability for sitting/supine was found to be  38%. These results show that the administration technique is very important and should not be underestimated.

Endothelium-Derived Hyperpolarizing Factor (EDHF) Mediates Acetylsalicylic Acid (Aspirin) Vasodilation of Pregnant Rat Mesenteric Arteries

From MDPI via Jisc Publications RouterHistory: accepted 2021-09-16, pub-electronic 2021-09-21Publication status: PublishedFunder: Seventh Framework Programme; Grant(s): 601852Funder: Icelandic Research Fund; Grant(s): 163369-051Acetylsalicylic acid (aspirin) exhibits a broad range of activities, including analgesic, antipyretic, and antiplatelet properties. Recent clinical studies also recommend aspirin prophylaxis in women with a high risk of pre-eclampsia, a major complication of pregnancy characterized by hypertension. We investigated the effect of aspirin on mesenteric resistance arteries and found outdiscovered the molecular mechanism underlying this action. Aspirin (10−12–10−6 M) was tested on pregnant rat mesenteric resistance arteries by a pressurized arteriography. Aspirin was investigated in the presence of several inhibitors of: (a) nitric oxide synthase (L-NAME 2 × 10−4 M); (b) cyclooxygenase (Indomethacin, 10−5 M); (c) Ca2+-activated K+ channels (Kca): small conductance (SKca, Apamin, 10−7 M), intermediate conductance (IKca, TRAM34, 10−5 M), and big conductance (BKca, paxilline, 10−5 M); and (d) endothelial-derived hyperpolarizing factor (high KCl, 80 mM). Aspirin caused a concentration-dependent vasodilation. Aspirin-vasodilation was abolished by removal of endothelium or by high KCl. Furthermore, preincubation with either apamin plus TRAM-34 or paxillin significantly attenuated aspirin vasodilation (p 0.05). For the first time, we showed that aspirin induced endothelium-dependent vasodilation in mesenteric resistance arteries through the endothelial-derived hyperpolarizing factor (EDHF) and calcium-activated potassium channels. By activating this molecular mechanism, aspirin may lower peripheral vascular resistance and be beneficial in pregnancies complicated by hypertension

Endothelium-derived hyperpolarizing factor (Edhf) mediates acetylsalicylic acid (aspirin) vasodilation of pregnant rat mesenteric arteries

Funding Information: Funding: This study was supported by the grants European Union 7th Framework Programme–FP7 (ASPRE Project # 601852); the Icelandic Research Fund (Rannís, no. 163369-051). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).Acetylsalicylic acid (aspirin) exhibits a broad range of activities, including analgesic, antipyretic, and antiplatelet properties. Recent clinical studies also recommend aspirin prophylaxis in women with a high risk of pre-eclampsia, a major complication of pregnancy characterized by hypertension. We investigated the effect of aspirin on mesenteric resistance arteries and found out-discovered the molecular mechanism underlying this action. Aspirin (10−12–10−6 M) was tested on pregnant rat mesenteric resistance arteries by a pressurized arteriography. Aspirin was investigated in the presence of several inhibitors of: (a) nitric oxide synthase (L-NAME 2 × 10−4 M); (b) cyclooxygenase (Indomethacin, 10−5 M); (c) Ca2+-activated K+ channels (Kca): small conductance (SKca, Apamin, 10−7 M), intermediate conductance (IKca, TRAM34, 10−5 M), and big conductance (BKca, paxilline, 10−5 M); and (d) endothelial-derived hyperpolarizing factor (high KCl, 80 mM). Aspirin caused a concentration-dependent vasodilation. Aspirin-vasodilation was abolished by removal of endothelium or by high KCl. Furthermore, preincubation with either apamin plus TRAM-34 or paxillin significantly attenuated aspirin vasodilation (p < 0.05). For the first time, we showed that aspirin induced endothelium-dependent vasodilation in mesenteric resistance arteries through the endothelial-derived hyperpolarizing factor (EDHF) and calcium-activated potassium channels. By activating this molecular mechanism, aspirin may lower peripheral vascular resistance and be beneficial in pregnancies complicated by hypertension.Peer reviewe

placental protein 13 pp13 induced vasodilation of resistance arteries from pregnant and nonpregnant rats occurs via endothelial signaling pathways

ABSTRACTPlacental protein 13 (PP13) induces hypotension in rats. This study aims to evaluate PP13 effects on isolated uterine arteries from nonpregnant and mid-pregnant rats. Vessels were isolated, cannulated, and pressurized to 50 mmHg within an arteriograph, preconstricted and exposed to increasing PP13 concentrations (10−13–10−8 M). PP13 elicited 38–50% arterial vasodilation with half-maximum response (EC50) = 1 pM. The relaxation was mediated by activating the endothelial-signaling pathways of prostaglandin and nitric oxide (NO). Accordingly, these results encourage evaluation of PP13 as a possible therapy for gestational diseases characterized by insufficient uteroplacental blood flow and/or maternal hypertension

Galectin 13 (PP13) facilitates remodeling and structural stabilization of maternal vessels during pregnancy

Funding Funding: This research was funded by Daniel Turnberg Fellowship, UK Academy of Medical Sciences and the EU COST action CA16113 – CkiniMark to M.S. This study was also sponsored in part by the European Union (FP7) through the ASPRE project (601852) to H.M., S.G. and T.D. were sponsored by Hananja ehf, and Icelandic Research Fund (Rannís), grant no. 163403-052. Publisher Copyright: © 2019 by the authors. Licensee MDPI, Basel, Switzerland.Galectins regulate cell growth, proliferation, differentiation, apoptosis, signal transduction, mRNA splicing, and interactions with the extracellular matrix. Here we focus on the galectins in the reproductive system, particularly on a group of six galectins that first appears in anthropoid primates in conjunction with the evolution of highly invasive placentation and long gestation. Of these six, placental protein 13 (PP13, galectin 13) interacts with glycoproteins and glycolipids to enable successful pregnancy. PP13 is related to the development of a major obstetric syndrome, preeclampsia, a life-threatening complication of pregnancy which affects ten million pregnant women globally. Preeclampsia is characterized by hypertension, proteinuria, and organ failure, and is often accompanied by fetal loss and major newborn disabilities. PP13 facilitates the expansion of uterine arteries and veins during pregnancy in an endothelial cell-dependent manner, via the eNOS and prostaglandin signaling pathways. PP13 acts through its carbohydrate recognition domain that binds to sugar residues of extracellular and connective tissue molecules, thus inducing structural stabilization of vessel expansion. Further, decidual PP13 aggregates may serve as a decoy that induces white blood cell apoptosis, contributing to the mother’s immune tolerance to pregnancy. Lower first trimester PP13 level is one of the biomarkers to predict the subsequent risk to develop preeclampsia, while its molecular mutations/polymorphisms that are associated with reduced PP13 expression are accompanied by higher rates of preeclampsia We propose a targeted PP13 replenishing therapy to fight preeclampsia in carriers of these mutations.Peer reviewe

Effect of doxycycline microencapsulation on buccal films : Stability, mucoadhesion and in vitro drug release

Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This research was funded by Rannsóknarsjóður Háskóla Íslands (University of Iceland Research Grand).The aim of this work was to stabilize doxycycline in mucoadhesive buccal films at room temperature (25◦C). Since doxycycline is susceptible to degradation such as oxidation and epimerization, tablets are currently the only formulation that can keep the drug fully stable at room temperature, while liquid formulations are limited to refrigerated conditions (4◦C). In this study, the aim was to make formulations containing subclinical (antibiotic) doxycycline concentration that can act as matrix metalloproteinase inhibitors (MMPI) and can be stored at temperatures such as 25◦C. Here, doxycycline was complexed with excipients using three techniques and entrapped into microparticles that were stored at 4◦C, 25◦C and 40◦C. Effect of addition of precomplexed doxycycline microparticles on films: stability mucoadhesion capacity, tensile strength, swelling index and in vitro release was studied. The complexation efficiency between drug-excipients, microparticles and films was studied using Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). Two of the films were found to be stable at 4◦C but the film containing microparticle composed of precomplexed doxycycline with β-cyclodextrin, MgCl2, sodium thiosulfate, HPMC and Eudragit® RS 12.5 was found to be stable at 25◦C until 26 weeks. The addition of microparticles to the films was found to reduce the mucoadhesive capacity, peak detachment force, tensile strength and elasticity, but improved the stability at room temperature.Peer reviewe