scholarly journals Comparison of Local and Systemic DTPA Treatment Efficacy According to Actinide Physicochemical Properties Following Lung or Wound Contamination in the Rat

2021 ◽  
Vol 12 ◽  
Author(s):  
Nina M. Griffiths ◽  
Anne Van der Meeren ◽  
Olivier Grémy
Keyword(s):  
Local Treatment ◽  
Experimental Studies ◽  
Occupational Accidents ◽  
Activity Levels ◽  
Entry Site ◽  
Potential Health ◽  
Wound Site ◽  
Internal Contamination ◽  
Treatment Regimens ◽  
Wound Contamination

Purpose: In cases of occupational accidents in nuclear facilities or subsequent to terrorist activities, the most likely routes of internal contamination with alpha-particle emitting actinides, such as plutonium (Pu) and americium (Am), are by inhalation or following wounding. Following contamination, actinide transfer to the circulation and subsequent deposition in skeleton and liver depends primarily on the physicochemical nature of the compound. The treatment remit following internal contamination is to decrease actinide retention and in consequence potential health risks, both at the contamination site and in systemic retention organs as well as to promote elimination. The only approved drug for decorporation of Pu and Am is the metal chelator diethylenetriaminepentaacetic acid (DTPA). However, a limited efficacy of DTPA has been reported following contamination with insoluble actinides, irrespective of the contamination route. The objectives of this work are to evaluate the efficacy of prompt local and/or systemic DTPA treatment regimens following lung or wound contamination by actinides with differing solubility. The conclusions are drawn from retrospective analysis of experimental studies carried out over 10 years.Materials and Methods: Rat lungs or wounds were contaminated either with poorly soluble Mixed OXide (U, Pu O2) or more soluble forms of Pu (nitrate or citrate). DTPA treatment was administered promptly after contamination, locally to lungs by insufflation of a powder or inhalation of aerosolized solution or by injection directly into the wound site. Intravenous injections of DTPA were given either once or repeated in combination with the local treatment. Doses ranged from 1 to 30 µmol/kg. Animals were euthanized from day 7–21 and alpha activity levels were measured in urine, lungs, wound, bone and liver for determination of decorporation efficacy.Results: Different experiments confirmed that whatever the route of contamination, most of the activity is retained at the entry site after insoluble MOX contamination as compared with contamination with more soluble forms which results in very low activities reaching the systemic compartment and subsequent retention in bone and liver. Several DTPA treatment regimens were evaluated that had no significant effect on either lung or wound levels compared with untreated animals. In contrast, in all cases systemic retention (skeleton and liver) was reduced and urinary excretion were enhanced irrespective of the contamination route or DTPA treatment regimen.Conclusion: The present study demonstrates that despite limitation of retention in systemic organs, different DTPA protocols were ineffective in removing insoluble actinides deposited in lungs or wound site. For moderately soluble actinides, local or intravenous DTPA treatment reduced activity levels both at contamination and at systemic sites.

scholarly journals Type II transmembrane serine proteases as potential targets for cancer therapy

2016 ◽  
Vol 397 (9) ◽  
pp. 815-826 ◽  
Author(s):  
Andrew S. Murray ◽  
Fausto A. Varela ◽  
Karin List
Keyword(s):  
Cancer Progression ◽  
Serine Proteases ◽  
Molecular Mechanisms ◽  
Inflammatory Cells ◽  
Activity Levels ◽  
Type Ii ◽  
Neoplastic Progression ◽  
Treatment Regimens ◽  
Proinflammatory Mediators ◽  
Transmembrane Serine Protease

Abstract Carcinogenesis is accompanied by increased protein and activity levels of extracellular cell-surface proteases that are capable of modifying the tumor microenvironment by directly cleaving the extracellular matrix, as well as activating growth factors and proinflammatory mediators involved in proliferation and invasion of cancer cells, and recruitment of inflammatory cells. These complex processes ultimately potentiate neoplastic progression leading to local tumor cell invasion, entry into the vasculature, and metastasis to distal sites. Several members of the type II transmembrane serine protease (TTSP) family have been shown to play critical roles in cancer progression. In this review the knowledge collected over the past two decades about the molecular mechanisms underlying the pro-cancerous properties of selected TTSPs will be summarized. Furthermore, we will discuss how these insights may facilitate the translation into clinical settings in the future by specifically targeting TTSPs as part of novel cancer treatment regimens.

scholarly journals AN ANAEROBIC-AEROBIC BIOLOGICAL TREATMENT OF WASTEWATER AT THE LOW-PRODUCTIVITY PLANT

2020 ◽  
pp. 122-131
Author(s):  
L.A. Fesik ◽  
◽  
N.V. Sorokina ◽  
E.А. Geraskina ◽  
T.S. Airapetian ◽  
...  
Keyword(s):  
Biological Treatment ◽  
Local Treatment ◽  
Experimental Studies ◽  
Treatment Plant ◽  
Domestic Wastewater ◽  
Treated Wastewater ◽  
Trophic Chain ◽  
Biological Purification ◽  
The Law

Abstract. The urgency of the problem of local biological treatment of domestic wastewater from housing in non-canalized areas with improving the quality of treated wastewater to the level of requirements for discharge into fishery bodies of water is considered. The analysis of the state of local wastewater treatment is given. Existing technological schemes and methods of local sewage, which are used for sewage treatment, are considered. The results of theoretical and experimental studies of a complex of a local anaerobic-aerobic biological treatment of domestic wastewater from housing in non-canalized areas at the low-productivity plants are presented. The results of theoretical and experimental researches of complex of local anaerobic-aerobic biological purification of domestic wastewater of habitation in non-canalized areas at the low-productivity plants are given. On the basis of the analysis of work and embodiment of low-productivity plants, used in home and foreign practice of local treatment of domestic wastewater the expediency of application flowing multistage anaerobic-aerobic biological purification of domestic wastewater with use of communities of attached and free-swimming microorganisms is shown. The proposed low-productivity plant, which includes a three-stage aerobic biological treatment of anaerobically treated wastewater is described. The use of ruff fillers for the retention of hydrobionts gives the opportunity to clear salvo discharge, rapid restoration of the activity of the ruff fillers (for example, in power outages). The ruff fillers make it possible to organize an appropriate trophic chain of hydrobionts, which dramatically reduces the amount of excess biomass and the removal of suspensions in treated wastewater. Using the experiments in laboratory conditions and at real industrial treatment plant of a new design there were received parameters of work of stages of anaerobic and aerobic biological purification, the law of nitrification and denitrification processes, the law of specific speed of oxidation of organic pollution in specific conditions of anaerobic-aerobic technology; the opportunity of reception of quality of treated wastewater at the level of the requirements of the specifications for dump of drains in fishing reservoirs is proved.

scholarly journals Safety and Clinical Effects of Switching From Intravenous to Oral Nimodipine Administration in Aneurysmal Subarachnoid Hemorrhage

2021 ◽  
Vol 12 ◽  
Author(s):  
Jennifer Göttsche ◽  
Nils Schweingruber ◽  
Julian Christopher Groth ◽  
Christian Gerloff ◽  
Manfred Westphal ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Oral Administration ◽  
Cerebral Artery ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Local Treatment ◽  
Transcranial Doppler Sonography ◽  
Clinical Effects ◽  
Mean Flow ◽  
Anterior Circulation ◽  
Treatment Regimens

Objective: Several guidelines recommend oral administration of nimodipine as vasospasm prophylaxis after aneurysmal subarachnoid hemorrhage (SAH). However, in clinical practice, the drug is administered orally and intravenously (i.v.), depending on clinical conditions and local treatment regimens. We have therefore investigated the safety and clinical effects of switching from i.v. to oral nimodipine therapy.Methods: Patients with aneurysmal SAH between January 2014 and April 2018 and initial i.v. nimodipine therapy, which was subsequently switched to oral administration, were included in this retrospective study. Transcranial Doppler sonography (TCD) of the vessels of the anterior circulation was performed daily. The occurrence of vasospasm and infarction during the overall course of the treatment was recorded. Statistical level of significance was set to p < 0.05.Results: A total of 133 patients (mean age 55.8 years, 65% female) initially received nimodipine i.v. after aneurysmal SAH, which was subsequently switched to oral administration after a mean of 12 days. There were no significant increases in mean flow velocities on TCD after the switch from i.v. to oral nimodipine administration regarding the anterior cerebral artery. For the middle cerebral artery, an increase from 62.36 to 71.78 cm/sec could only be detected in the subgroup of patients with infarction. There was no clustering of complicating events such as new-onset vasospasm or infarction during or after the switch.Conclusions: Our results do not point to any safety concerns when switching nimodipine from initial i.v. to oral administration. Switching was neither associated with clinically relevant increases in TCD velocities nor other relevant adverse events.

scholarly journals Understanding the Metabolic Fate and Bioactivity of Dietary Anthocyanins

Proceedings ◽  
2020 ◽  
Vol 36 (1) ◽  
pp. 64
Author(s):  
Netzel ◽  
Wright ◽  
Sultanbawa ◽  
Netzel
Keyword(s):  
Human Subjects ◽  
Experimental Studies ◽  
Grape Juice ◽  
Grape Pomace ◽  
Metabolic Fate ◽  
Healthy Human ◽  
Potential Health ◽  
Beneficial Effects ◽  
Red Grape

Anthocyanins are plant pigments and dietary phytochemicals, and may have potential health benefits. There is emerging evidence from epidemiological and experimental studies that suggests a higher consumption of anthocyanin-rich foods is associated with a reduced risk of heart disease and diabetes. To better understand the observed beneficial effects of anthocyanins and their underlying mode of action, bioavailability and metabolic fate needs to be studied in more detail. Healthy human subjects (10–12 in two different studies) received red grape pomace (700 mg anthocyanins/mainly as malvidin-3-glucoside) or Queen Garnet plum (QGP) juice (426 mg anthocyanins/mainly as cyanidin-3-glucoside) and an anthocyanin-free control in a randomised crossover design. Malvidin- and cyanidin-glycosides are common in many fruits and beverages such as red grapes, red grape juice, red wine, blueberry, cherry, elderberry, (Japanese) plum and are therefore of dietary significance. 24-hr urine samples were collected and analysed for anthocyanins and metabolites by UHPLC-PDA-MS. Methylated, glucuronidated and sulphated anthocyanins could be identified as characteristic metabolites in both studies. Furthermore, the increase in urinary hippuric acid (microbial/hepatic metabolite) was considerable in both studies after the consumption of red grape pomace or QGP juice (1.8–4.5-fold vs. control; p < 0.05). These findings suggest that structurally different anthocyanins are exposed to a similar extensive metabolism by enzymes and the gut microbiome and that the generated metabolites are most likely the bioactive compounds in vivo. Therefore, more human studies are warranted to investigate the metabolic fate of dietary anthocyanins and the bioactivity of generated metabolites.

EXPERIMENTAL SURVIVAL STUDIES OF SPOROTHRIX SCHENCKII IN A MEAT PRODUCT1

1973 ◽  
Vol 36 (6) ◽  
pp. 311-314 ◽  
Author(s):  
J. H. Scharding ◽  
D. C. Kelley ◽  
J. E. Cook ◽  
D. H. Kropf
Keyword(s):  
High Temperatures ◽  
Health Hazard ◽  
Experimental Studies ◽  
Sporothrix Schenckii ◽  
Test Model ◽  
Potential Health ◽  
Cooking Process ◽  
Potential Health Hazard ◽  
Survival Studies

The literature includes a few reports on the ability of the fungus Sporothrix schenckii to survive at high temperatures, and one suggests that it could survive processing procedures used to manufacture frankfurters. Reported are studies to determine the extent that S. schenckii could survive processing procedures used by most manufacturers of commercial frankfurters. A frankfurter test model was devised to approximate the length diameter, and cooking characteristics of a commercial frankfurter. Uncooked emulsion was inoculated with the organism and recovery was attempted throughout the experimental cooking process. In 32% of the experimental studies, the maximum times and temperatures for positive recovery of the organism met or exceeded the processing standards used by most manufacturers. Thus, S. schenckii may survive in commercial frankfurters and be a potential health hazard.

Improvement of Efficiency of Waste Water Treatment from Metals Using Flotation Combines

2020 ◽  
Vol 24 (10) ◽  
pp. 4-7
Author(s):  
B.S. Ksenofontov ◽  
A.S. Kozodayev ◽  
R.A. Taranov ◽  
M.S. Vinogradov
Keyword(s):  
Waste Water ◽  
Heavy Metals ◽  
Water Treatment ◽  
Waste Water Treatment ◽  
Local Treatment ◽  
Experimental Studies ◽  
Treatment Unit ◽  
Reagent Treatment ◽  
Treatment Facilities ◽  
Technical Solutions

The work deals with the use of flotation combines for the treatment of waste water from heavy metals. The analysis of various methods of treatment of waste water from heavy metals was carried out, which revealed the most promising technical solutions with their possible implementation for modernization of existing treatment facilities of the enterprise. Experimental studies of several versions of technological schemes were carried out on the basis of which a technological scheme of waste water treatment was selected, including all positions of equipment existing at local treatment facilities, and supplemented with a reagent treatment unit, treatment in a flotation complex using reagents, application of filters and pH correction.

NON INVASIVE DELIVERY OF PROTEIN AND PEPTIDE DRUGS: A REVIEW

2017 ◽  
Vol 10 (8) ◽  
pp. 25 ◽  
Author(s):  
P.k. Lakshmi ◽  
D Prasanthi ◽  
B Veeresh
Keyword(s):  
Drug Delivery ◽  
Drug Transport ◽  
Local Treatment ◽  
Oral Formulation ◽  
Systemic Delivery ◽  
Peptide Drugs ◽  
Administration Routes ◽  
Treatment Regimens ◽  
Non Invasive ◽  
Proteins And Peptides

Till recent, injections remained the most common route for administration of protein and peptide drugs because of their poor bioavailability in the other routes. Because it is generally recognized that injection based delivery is a major impediment to the commercial success of therapeutic proteins and peptides, research in both academia and industry continues to focus on ways to overcome this problem. Possible non-parenteral administration routes for delivery of peptide and protein drugs include oral, nasal, ocular, transdermal, rectal, colonic, and vaginal route. The large surface area associated with most of these routes makes them attractive targets for drug delivery. While non-invasive administration by these routes is considered a more logical and achievable option for local treatment regimens, systemic delivery of proteins and peptides is significantly more challenging. In spite of effort made on the development of drugs for these routes, most of the successes fail to address how the technology will be transformed to a commercial product. The only notable exceptions have been the successful commercialization of nasal formulations for systemic delivery of a limited number of therapeutic peptides, and recent regulatory approvals of both pulmonary and buccal delivery systems for systemic delivery of insulin and an oral formulation of a small peptide analog, cyclosporine, have been commercialized. The present review aims to discuss the potential non-invasive routes of protein and peptide drug delivery. The factors which will affect drug transport and the bioavailability of proteins administered through these routes is also emphasized

scholarly journals Identification of Alpha Interferon-Induced Envelope Mutations of Hepatitis C VirusIn VitroAssociated with Increased Viral Fitness and Interferon Resistance

2013 ◽  
Vol 87 (23) ◽  
pp. 12776-12793 ◽  
Author(s):  
Stéphanie B. N. Serre ◽  
Henrik B. Krarup ◽  
Jens Bukh ◽  
Judith M. Gottwein
Keyword(s):  
Hepatitis C ◽  
Viral Entry ◽  
Experimental Studies ◽  
Viral Fitness ◽  
Alpha Interferon ◽  
Close Link ◽  
Treatment Regimens ◽  
Viral Spread ◽  
Infection Resistance

Alpha interferon (IFN-α) is an essential component of innate antiviral immunity and of treatment regimens for chronic hepatitis C virus (HCV) infection. Resistance to IFN might be important for HCV persistence and failure of IFN-based therapies. Evidence for HCV genetic correlates of IFN resistance is limited. Experimental studies were hampered by lack of HCV culture systems. Using genotype (strain) 1a(H77) and 3a(S52) Core-NS2 JFH1-based recombinants, we aimed at identifying viral correlates of IFN-α resistancein vitro. Long-term culture with IFN-α2b in Huh7.5 cells resulted in viral spread with acquisition of putative escape mutations in HCV structural and nonstructural proteins. Reverse genetic studies showed that primarily amino acid changes I348T in 1a(H77) E1 and F345V/V414A in 3a(S52) E1/E2 increased viral fitness. Single-cycle assays revealed that I348T and F345V/V414A enhanced viral entry and release, respectively. In assays allowing viral spread, these mutations conferred a level of IFN-α resistance exceeding the observed fitness effect. The identified mutations acted in a subtype-specific manner but were not found in genotype 1a and 3a patients, who failed IFN-α therapy. Studies with HCV recombinants with different degrees of culture adaptation confirmed the correlation between viral fitness and IFN-α resistance. In conclusion,in vitroescape experiments led to identification of HCV envelope mutations resulting in increased viral fitness and conferring IFN-α resistance. While we established a close link between viral fitness and IFN-α resistance, identified mutations acted via different mechanisms and appeared to be relatively specific to the infecting virus, possibly explaining difficulties in identifying signature mutations for IFN resistance.

scholarly journals Nutrition role in the well-being of people during Covid 19 pandemic-A review article

2021 ◽  
Vol 11 (2) ◽  
pp. 237-240
Author(s):  
Abhishek Lachyan ◽  
Randhir S Gendeh a/l Jekinder Singh ◽  
Abubakar Mannir ◽  
Pooja Nilgar ◽  
Rafdzah Ahmad Zaki ◽  
...  
Keyword(s):  
Vitamin C ◽  
Well Being ◽  
Review Article ◽  
Elevated Risk ◽  
World Health ◽  
Activity Levels ◽  
Long Chain Fatty Acids ◽  
Omega 3 ◽  
Potential Health ◽  
Health Experts

The worldwide health catastrophe caused by the Coronavirus Disease 2019 (COVID-19) pandemic has startled world health experts. Obesity and poor physical activity levels were shown to be elevated risk factors for COVID-19 affection and physiopathology, indicating that the COVID-19 lockdown encouraged harmful dietary changes and increases in body weight in the community. Furthermore, malnutrition and deficiencies in vitamin C, D, B12, selenium, iron, omega-3, and medium and long-chain fatty acids were found in hospitalized COVID-19 patients, emphasizing the potential health benefits of vitamin C and D treatments. More research is needed to determine the full function and consequences of diet in the prevention and treatment of COVID-19 infected individuals.

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