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McGinnis Finch opublikował 1 rok, 8 miesięcy temu
This concept study presents a potential alternative membrane for pharmaceutical transdermal analysis, providing many benefits over existing options. Bepotastine (BPT) is a H1-receptor antagonist. It is used as a besilate salt in ophthalmic solution for allergic conjunctivitis, and orally for the treatment of allergic rhinitis and utricaria/pruritus. Its systematic forced degradation study is unreported. The same was carried out in different conditions prescribed by International Conference on Harmonisation. The stressed solutions were subjected to reversed phase liquid chromatographic analysis, and BPT was observed to be labile under photobasic condition only, yielding five photodegradation products. The structures of the latter were elucidated from data generated using liquid chromatography-high resolution mass spectrometry and multi-stage mass spectrometry. Of the five, four products were further isolated and subjected to nuclear magnetic resonance spectroscopy to justify the proposed structures. Two of them, with similar accurate mass, were additionally and unambiguously characterized from their heteronuclear multiple bond correlation data, hydrogen deuterium exchange mass data, and quantum chemical analysis using density function theory calculations. One degradation product had a structure that could only be explained by unusual rearrangement involving conversions of N-oxide into hydroxylamine, similar to Meisenheimer rearrangement. The physicochemical, as well as absorption, distribution, metabolism, excretion and toxicity properties of BPT and its characterized photodegradation products were evaluated in silico by ADMET Predictor™ software. Previously, 1 mL of purified water (hyposmotic) or saline (isosmotic) which dissolved 200 μM of FITC-dextran (FD-4), a non-absorbable marker, was orally administered to rats, and luminal concentration-time profile of FD-4 was directly measured. In this study, at first, luminal FD-4 concentration was measured after oral administration of 0.5 mL of FD-4 purified water solution (200 μM). Then, kinetic analysis was conducted to calculate the fluid volume that passed through each segment of the gastrointestinal tract (Vfluid), based on the luminal FD-4 concentration-time profiles obtained from three different administration groups. In the group of 1 mL purified water administration, most of administered water was absorbed quickly from the duodenum and upper jejunum, whereas group of saline administration (1 mL) showed only a little amount of absorbed in the upper small intestine. In 0.5 mL purified water group, Vfluid in the stomach was approximately half compared to that in 1 mL purified water group. However, for small intestine, almost the same values of Vfluid were obtained regardless of the dose-volume. Our findings are valuable to improve the quality of in vitro predictive dissolution tools and/or in silico simulation for predicting oral drug absorption. Cantharidin (CTD), a natural Chinese medicine constituent extracted from mylabris, is a potent drug against hepatocellular carcinoma (HCC). However, the clinical application of CTD was limited due to its toxicity and low-solubility. In this work, a novel CTD-loaded liposome modified with 3-succinyl-30-stearyl glycyrrhetinic acid (18-GA-Suc-CTD-Lip) was prepared in order to enhance liver-targeting efficiency and anti-tumor activity. 18-GA-Suc-CTD-Lip and CTD-Lip were successfully prepared by film dispersion method and totally characterized. The anti-tumor effects in vitro were evaluated by cell proliferation inhibition assay, transwell assay, cell cycle analysis and an apoptosis test. Pharmacokinetic and biodistribution were all investigated to precisely reveal liver-targeting efficiency of 18-GA-Suc-CTD-Lip in vivo. The IC50 values of 18-GA-Suc-CTD-Lip in HepG2 (3.417 ± 0.165 nmol/L) and Huh-7 (4.478 ± 0.409 nmol/L) cells were much lower than that of CTD-Lip, indicating that anti-tumor effects of 18-GA-Suc-CTD-Lip were remarkable due to the modification of 18-GA-Suc. The maximum concentration in the liver of 18-GA-Suc-CTD-Lip (1.72 ± 0.14 μg/g) was more than twice CTD-Lip (0.75 ± 0.08 μg/g) at 30 min, illustrating that 18-GA-Suc-CTD-Lip possesses excellent liver-targeting efficiency. Conclusively, 18-GA-Suc-CTD-Lip could be a potential liver-targeting anti-tumor drug for HCC. The notochord is an embryonic tissue that acts as a hydrostatic skeleton until ossification begins in vertebrates. It is composed of outer sheath cells and inner vacuolated cells, which are generated from a common pool of disc-shaped precursors. Notochord extension during early embryogenesis is driven by the growth of vacuolated cells, reflecting in turn the expansion of their inner vacuole. Here we use desmogon, a novel desmosomal cadherin, to follow notochord development and regeneration in medaka (Oryzias latipes). We trace desmogon+ disc-shaped precursors at the single cell level to demonstrate that they operate as unipotent progenitors, giving rise to either sheath or vacuolated cells. We reveal that once specified, vacuolated cells grow asynchronously and drive notochord expansion bi-directionally. Additionally, we uncover distinct regenerative responses in the notochord, which depend on the nature of the injury sustained. By generating a desmogon CRISPR mutant we demonstrate that this cadherin is essential for proper vacuolated cell shape and therefore correct notochord and spine morphology. Our work expands the repertoire of model systems to study dynamic aspects of the notochord in vivo, and provides new insights in its development and regeneration properties. New drugs for the treatment of human leishmaniasis are urgently needed, considering the limitations of current available options. However, pre-clinical evaluation of drug candidates for leishmaniasis is challenging. The use of luciferase-expressing parasites for parasite load detection is a potentially powerful tool to accelerate the drug discovery process. We have previously described the use of Leishmania amazonensis mutants expressing firefly luciferase (Luc2) for drug testing. Here, we describe three new mutant L. amazonensis lines that express different variants of luciferases NanoLuc, NanoLuc-PEST and RedLuc. These mutants were evaluated in drug screening protocols. NanoLuc-parasites, in spite of high bioluminescence intensity in vitro, were shown to be inadequate in discriminating between live and dead parasites. Bioluminescence detection from intracellular amastigotes expressing NanoLuc-PEST, RedLuc or Luc2 proved more reliable than microscopy to determine parasite killing. Increased sensitivity was observed in vivo with RedLuc-expressing parasites as compared to NanoLuc-expressing L. amazonensis. Our data indicates that NanoLuc is not suitable for in vivo parasite burden determination. Additionally, RedLuc and the conventional luciferase Luc2 demonstrated equivalent sensitivity in an in vivo model of cutaneous leishmaniasis. Mosquito-borne Zika virus (ZIKV) was recently introduced into the Americas and now has the potential to spill back into a sylvatic cycle in the region, likely involving non-human primates and Aedes, Haemagogus, and Sabethes species mosquitoes. We investigated potential routes of mosquito-borne virus exchange between urban and sylvatic transmission cycles by characterizing mosquito communities in three urban forest parks that receive heavy traffic from both humans and monkeys in Manaus, Brazil. Parks were stratified by both distance from the urban-forest edge (0, 50, 100, and 500 m) and relative Normalized Difference Vegetation Index (NDVI) (low, medium, or high), and mosquitoes were sampled at randomly selected sites within each stratum using BG-Sentinel traps. Additionally, temperature, relative humidity, and other environmental data were collected at each site. A total of 1,172 mosquitoes were collected from 184 sites sampled in 2018, of which 98 sites were resampled in 2019. Using park as the unit of replia multiple bridge vectors in Brazilian urban forest parks. These parks may also provide refugia for both Ae. albopictus and Ae. aegypti from mosquito control programs. V.Q fever is a widespread zoonotic disease caused by Coxiella burnetii that most commonly infects not only a variety of mammals but also arthropods and in particularly ticks. The aim of this study was to detect C. burnetii infection in camels including ixodid ticks using serological and molecular assays. Between July 2018 to June 2019, blood samples from 184 male and female camels (Camelus dromedarius) were collected from 3 regions of South-East Algeria and serum samples were tested for antibodies against Coxiella burnetii using indirect enzyme-linked immunosorbent assay (ELISA) kit. The positive sera and a total of 60 ticks were tested by quantitative PCR (qPCR) for detection of C. burnetii with primers and probes specific to the transposon-like repetitive region (IS1111 gene). Positive samples were genotyped by amplification and sequencing of partial sequences based on the IS1111 gene. The seroprevalence of antibodies against C. burnetii was 75.5%. Statistical analysis pointed out three potential risk factors associated with Q fever infection geographic location, age class and season. No positive DNA of camel blood sample was observed. However, five Hyalomma dromedarii, one H. impeltatum and one H. excavatum tick species were detected positive for Coxiella burnetii DNA by qPCR, with an overall prevalence rate of 11.66% (7/60). The revealed Algerian strains by phylogenetic and comparative analysis of the IS1111 nucleotide sequences were clustered with several pathogenic C. burnetii strains isolated from ticks, human, and cattle located in Tunisia, Greece and in some Mediterranean countries, respectively. The study results clearly indicate that camels and their ticks in Algeria may play an important role as a reservoir for C. burnetii and can be considered as a significant source of Q fever transmission to other animal species and humans. INTRODUCTION The work has been reported in line with the SCARE criteria. Thoracoabdominal impalement injuries are uncommon and very few cases have been reported. Impalement injuries result when a rigid object penetrates and remains lodged within the body. It has complex anesthetic and surgical management. We describe the successful surgical and anesthetic management of a major impalement injury of the torso. CASE REPORT A 21-year old male construction worker brought to emergency with two iron construction rods impaled in torso due to fall from 2nd floor while working. Both were 1 m long and 12 mm in diameter. One had penetrated from right anterior axillary fold, deep to pectoralis major, exiting from left sternal border. Second entered below the tip of right scapula and exiting from left of xiphoid process. ATLS protocols were followed and patient resuscitated, immediately shifted to operating room, intubated in semi left lateral position. Rod impacted in right pectoral area was superficial with no injury to ribs or pleural space. Other was removed through laparotomy, thoracotomy and Hepatotomy, as it had pierced diaphragm and liver. Post-operative recovery was uneventful. DISCUSSION Resuscitation and close monitoring prior to and during surgery are vital with anticipation of major organ and vascular injuries. Hypovolemia should be corrected in the OR. Progressive dyspneacan be the most important symptom in patients with penetrating chest injury. CONCLUSION Penetrating abdominothoracic injuries demand immediate life-saving measures, appropriate resuscitative care, urgent shifting of patient to tertiary care center, prompt diagnosis and immediate surgical intervention. Regulation of safety rules at construction site and early intervention in case of accidents can improve the patient outcome and minimize mortality.


