scholarly journals Cryptic Plasmodium chronic infections: was Maurizio Ascoli right?

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Wuelton Monteiro ◽  
José Diego Brito-Sousa ◽  
Aleix Elizalde-Torrent ◽  
Camila Bôtto-Menezes ◽  
Gisely Cardoso Melo ◽  
...  
Keyword(s):  
Research Community ◽  
New Drugs ◽  
Chronic Infections ◽  
Knowledge Gaps ◽  
Internal Organs ◽  
Malaria Research ◽  
Italian Physician

AbstractCryptic Plasmodium niches outside the liver possibly represent a major source of hypnozoite-unrelated recrudescences in malaria. Maurizio Ascoli, an Italian physician and scientist, suggested that infection was maintained as a result of the persistence of endoerythrocytic parasites in the circulatory bed of some internal organs, mainly the spleen. This would explain a proportion of the recurrences in patients, regardless of the Plasmodium species. Ascoli proposed a method that included the co-administration of adrenaline, in order to induce splenic contraction, and quinine to clear expelled forms in major vessels. Driven by controversy regarding safety and effectiveness, along with the introduction of new drugs, the Ascoli method was abandoned and mostly forgotten by the malaria research community. To date, however, the existence of cryptic parasites outside the liver is gaining supportive data. This work is a historical retrospective of cryptic malaria infections and the Ascoli method, highlighting key knowledge gaps regarding these possible parasite reservoirs.

MICROSCOPIC CHANGES IN THE INTERNAL ORGANS OF WHITE MICE DURING EXPERIMENTAL IRON (IV) CLATHROCHELATE TOXICOSIS

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
B. V. Borysevych ◽  
◽  
V. V. Lisova ◽  
I. M. Derkach ◽  
S. S. Derkach ◽  
...  
Keyword(s):  
Biological Response ◽  
Organ Damage ◽  
The Body ◽  
New Drugs ◽  
Laboratory Animals ◽  
Internal Organs ◽  
Experimental Drug ◽  
Liver And Kidney ◽  
Preclinical And Clinical Studies ◽  
First Time

Iron (IV) clathrochelate based on a macrobicyclic ligand of the hexahydrazide type is a unique compound that contains iron in a rare high valence IV. Preclinical and clinical studies of this complex, which were started for the first time in Ukraine, have an important theoretical and practical consequence as this complex can be recommended as an active substance in iron-containing drugs with antianemic action. In conducting preclinical studies of new drugs, pathomorphological studies are important because they are a necessary step in studying the biological response of animals to the action of test substances. It was found that some pathological changes develop in the body of white mice under conditions of experimental acute and chronic iron (IV) clathrochelate intoxication. They correlated with the dose of the test compound. During chronic intoxication, the microscopic changes in the liver and kidney of white mice treated with iron (IV) clathrochelate at a dose of 1/10 DL50 were similar to the microscopic changes in the liver and kidney of mice treated with the experimental drug at a dose of 1/5 DL50. However, the severity of these changes was lower, reflecting a lower degree of organ damage. In the myocardium of mice treated with iron (IV) clathrochelate at a dose of 1/5 DL50 on the 10th day, as in acute iron (IV) clathrochelate poisoning, only edema was recorded. The prospects for further research are the study of microscopic changes in the organs of laboratory animals of other species during experimental iron (IV) clathrochelate toxicosis.

About syphilitic diseases of internal organs

1930 ◽  
Vol 26 (1) ◽  
pp. 15-31
Author(s):  
R. A. Luria
Keyword(s):  
Medical Science ◽  
Chronic Infections ◽  
Internal Organs

The very fact that I have the high honor to speak here, in the oldest center of medical science, in Utrecht, in your highly respected Society for Syphilitic Diseases of Internal Organs, testifies to the great interest and significant urgency of the problem of visceral syphilis. Three chronic infections are the cause of a large number of lesions of internal organs - tuberculosis, malaria and syphilis - and of them syphilis really deserves special attention, since it is about it that the doctor most often forgets, and meanwhile, at the time of recognizing a syphilitic disease of internal organs, it often means not only save the patient, but also experience the greatest pleasure of medical creativity and the joy of fulfilling the high duty of a doctor.

scholarly journals Future Directions for the World Climate Research Programme

Eos ◽  
2015 ◽  
Vol 43 ◽  
Author(s):  
Guy Brasseur ◽  
David Carlson
Keyword(s):  
Research Programme ◽  
Research Community ◽  
Knowledge Gaps ◽  
Future Directions ◽  
Climate Research ◽  
Clear Sense ◽  
User Communities ◽  
The World

The worldwide climate research community has talent, dedication, and a clear sense of knowledge gaps. It needs to close those gaps and convey its messages effectively to user communities.

scholarly journals P2-receptors as promising target for future drugs

2016 ◽  
Vol 97 (1) ◽  
pp. 135-141
Author(s):  
A U Ziganshin
Keyword(s):  
P2 Receptors ◽  
New Drugs ◽  
Internal Organs ◽  
Promising Target ◽  
Pathophysiological Role ◽  
Specific Receptors ◽  
Medical University ◽  
Near Future ◽  
University Laboratory

Now it is recognized that extracellular adenosine triphosphate (ATP), along with certain other purine and pyrimidine compounds is capable to regulate many intracellular processes by affecting specific receptors - P2-receptors. These receptors are widely distributed in the organs and tissues of humans and animals. It has been shown that P2-receptors are involved in the vascular tone maintenance, nerve transmission modulation, hemostasis regulation and functions of many internal organs. P2-receptors wide variety and broad representation makes them very attractive as potential targets for new drugs with the original mechanism of action. About 20 years ago in the Kazan State Medical University laboratory was created and research group on studying the fundamental and applied aspects of the P2-receptors was formed. Professor A.U. Ziganshin, a disciple and colleague of professor G. Burnstock, leads this group. In this article, an overview of research carried out by the author or under his supervision over the past two decades to study the physiological and pathophysiological role of P2-receptors in humans and animals, as well as the evaluation of these receptors as potential targets for action of new drugs, is given. In particular, it describes the work to identify new and effective P2-receptors antagonists, the role and characteristics of ecto-ATPase activity in different tissues are described, an overview of studies to assess the unique hypersensitivity of P2-receptors at low temperatures is given. Also studies on assessing the presence and functional role of P2-receptors in the pregnant human uterus, inflamed fallopian tubes, various blood vessels are presented in summary form. Obviously, due to the growing interest of many pharmaceutical companies to this area, in the near future we can expect new drugs, which are P2-receptors agonists or antagonists and are effective in treatment of various human diseases.

scholarly journals Rutin, a Natural Inhibitor of IGPD Protein, Inhibits the Biofilm Formation in Staphylococcus xylosus ATCC700404

2019 ◽  
Author(s):  
God’spower Bello-Onaghise ◽  
Xing Xiaoxu ◽  
Zhou Yonghui ◽  
Qu Qianwei ◽  
Cui Wenqiang ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Enzyme Inhibitor ◽  
Biological Activities ◽  
Inhibitory Effect ◽  
Vital Role ◽  
New Drugs ◽  
Resistant Bacteria ◽  
Chronic Infections ◽  
Staphylococcus Xylosus ◽  
Key Enzyme

ABSTRACTThe biofilm of bacteria plays an important role in antibiotic resistance and chronic infection. Thus, in order to solve the problem of resistant bacteria, it is very important to find new drugs that can inhibit the formation of biofilms. In recent years, researchers have shifted their attention to natural products. As a flavonoid, rutin has been reported to have a variety of biological activities, interestingly, in this study, the inhibitory effect of rutin on the biofilm of Staphylococcus xylosus was investigated. We confirmed that rutin could effectively inhibit the biofilm formation of S. xylosus, then, for the sake of discussion on how it interferes with the biofilm formation, the interaction between rutin and imidazolyl phosphate dehydratase (IGPD) which has been identified as the key enzyme that plays a vital role in the process of biofilm formation was analyzed by molecular docking, the results showed that rutin had a strong affinity with IGPD, it occupied the hydrophobic cavity of the active center forming four hydrogen bonds and many other interactions. In addition, we proved that rutin was able to combine with IGPD using SPR technique. Therefore, we determined the enzyme activity and histidine content of IGPD, the result indicated that rutin could simultaneously inhibit the activity of IGPD and abrogate the synthesis of histidine. Interestingly, the hisB gene encoding for IGPD and IGPD in S. xylosus were also significantly inhibited when the bacterial culture was treated with rutin. Taken together, the results have provided evidence that rutin is a natural drug that has the ability to interfere with the formation of biofilm in S. xylosus. It is therefore a potential enzyme inhibitor of IGPD.Author’s SummaryStaphylococcus xylosus has been isolated from a variety of infections, and the biofilm formed by S. xylosus can help the bacteria evade the immune system of the host and cause chronic infections. Here, we dealt with this menace by establishing a highly effective drug with the ability to interfere with the process involved in the formation of biofilm in S. xylosus. IGPD has been reported to be directly involved in the formation of biofilm in Staphylococcus xylosus and it is known to be present in a variety of microorganisms. Based on this study, we developed a drug therapy targeting IGPD and at the same time interfere with the formation of biofilm in S. xylosus

scholarly journals Searching Hit Potential Antimicrobials in Natural Compounds Space Against Biofilm Formation

2020 ◽  
Author(s):  
Roberto Pestana ◽  
Jorge Leyva ◽  
Juvenal Yosa
Keyword(s):  
Biofilm Formation ◽  
Potential Method ◽  
New Drugs ◽  
Resistant Bacteria ◽  
Chronic Infections ◽  
Aconitic Acid ◽  
Starting Point ◽  
In Silico Studies ◽  
Biofilm Development

Biofilms are communities of microorganisms that can colonize biotic and abiotic surfaces playing a significant role in the persistence of bacterial infection and antibiotic resistance. About 65% and 80% of microbial and chronic infections are produced by biofilm formation. The increase in infections by multi-resistant bacteria draws attention to the discovery of new drugs based on natural inhibitory molecules. The inhibition of diguanylate cyclases (DGCs), the enzyme implicated in the synthesis of the second messenger, cyclic diguanylate (c-di-GMP), involved the biofilm formation, represents a potential method for preventing the biofilm development. It has been extensively studied using PleD protein as a model of DGC for in silico studies as virtual screening and as a model for in vitro studies in biofilms formation. In the present study 224205 molecules from natural products database, ZINC15 has been evaluated through molecular docking and molecular dynamic simulation, our result suggests trans-Aconitic acid (TAA) as a possible starting point for hit-to-lead methodologies to obtain new molecules capable of inhibiting the PleD protein and hence blocking the biofilm formation.

scholarly journals Complex Polypathology Infectious, Rheumatological, Neurological and Orthopedic – Real Challenge for Functional Rehabilitation - Case Report

2020 ◽  
Vol 26 (2) ◽  
pp. 52-57
Author(s):  
Libu Cristiana ◽  
Iliescu Mădălina Gabriela ◽  
Bobe Zoe Maria ◽  
Arghir Oana Cristina ◽  
Bilous Dana-Maria ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Infectious Diseases ◽  
Clinical Manifestations ◽  
New Drugs ◽  
Chronic Infections ◽  
Functional Rehabilitation ◽  
European League Against Rheumatism ◽  
Insidious Onset ◽  
The Common ◽  
Real Challenge

Abstract Introduction. Infectious and autoimmune rheumatic diseases (ARDs) are closely linked. Apart from the challenging, sometimes differential, diagnosis between these conditions, it is recognized that microbes play an important role in the pathogenesis of the latter. Material and method. We present the case of a 45-year-old female patient from our rehabilitation department, with complex pathology (infectious, neurological, rheumatological and orthopedic pathology) that began more than 15 years ago. The patient’s pathological history began insidiously at theage of 30 when she was diagnosed with neurotoxoplasmosis. She received anticoagulant, antiepileptic, steroidal, antibiotic and antihelmintic treatment. After four years, the patient shows insidious onset of inflammatory pain in the large joints and in 2010 is diagnosed with seropositive rheumatoid arthritis, according to American College of Rheumatism/European League against rheumatism (ACR/EULAR) criteria with symmetric impairment of the large joints (shoulder, elbow, hip, knee, ankle). Despite the treatment with disease-modifying anti-rheumatic drugs (DMARDs) received, in the following years she needed 4 arthroplasties in the large joints due to osteonecrosis. Conclusions. On clinical grounds, infections, especially chronic infections, can cause a plethora of autoimmune phenomena, thus mimicking ARDs. Therefore, the differential diagnosis between ARDs and infectious diseases is sometimes challenging as they often display similar clinical manifestations. It is highlighted that the immune system can be our friend or our foe considering that its function and dysregulation are the common denominators in autoimmune and infectious diseases. In the era of new drugs and new therapeutic strategies, safety of the patients should always be our first concern.

scholarly journals Trace incorporation of heavy water reveals slow and heterogeneous pathogen growth rates in cystic fibrosis sputum

2015 ◽  
Vol 113 (2) ◽  
pp. E110-E116 ◽  
Author(s):  
Sebastian H. Kopf ◽  
Alex L. Sessions ◽  
Elise S. Cowley ◽  
Carmen Reyes ◽  
Lindsey Van Sambeek ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Heavy Water ◽  
Growth Rates ◽  
Physiological State ◽  
Full Range ◽  
New Drugs ◽  
Chronic Infections ◽  
Preclinical Development ◽  
Laboratory Models

Effective treatment for chronic infections is undermined by a significant gap in understanding of the physiological state of pathogens at the site of infection. Chronic pulmonary infections are responsible for the morbidity and mortality of millions of immunocompromised individuals worldwide, yet drugs that are successful in laboratory culture are far less effective against pathogen populations persisting in vivo. Laboratory models, upon which preclinical development of new drugs is based, can only replicate host conditions when we understand the metabolic state of the pathogens and the degree of heterogeneity within the population. In this study, we measured the anabolic activity of the pathogenStaphylococcus aureusdirectly in the sputum of pediatric patients with cystic fibrosis (CF), by combining the high sensitivity of isotope ratio mass spectrometry with a heavy water labeling approach to capture the full range of in situ growth rates. Our results revealS. aureusgeneration times with a median of 2.1 d, with extensive growth rate heterogeneity at the single-cell level. These growth rates are far below the detection limit of previous estimates of CF pathogen growth rates, and the rates are slowest in acutely sick patients undergoing pulmonary exacerbations; nevertheless, they are accessible to experimental replication within laboratory models. Treatment regimens that include specific antibiotics (vancomycin, piperacillin/tazobactam, tobramycin) further appear to correlate with slow growth ofS. aureuson average, but follow-up longitudinal studies must be performed to determine whether this effect holds for individual patients.

scholarly journals Pathological Aspects of Haemonchosis in Goats and Sheeps

2020 ◽  
Vol 30 (2) ◽  
Author(s):  
Riza Zainuddin Ahmad ◽  
Rida Tiffarent
Keyword(s):  
Haemonchus Contortus ◽  
Mononuclear Cells ◽  
Clinical Symptoms ◽  
Severe Anaemia ◽  
Economic Losses ◽  
Pathological Findings ◽  
Chronic Infections ◽  
Internal Organs ◽  
Large Numbers ◽  
High Prevalence

<p class="awabstrak2">Haemonchosis in sheep and goats has a high prevalence rate in several regions in Indonesia and causes economic losses. The purpose of this paper is to explain the clinical symptoms and pathological aspects of <em>Haemonchus contortus</em> infection so that knowledge is expected to help in controlling haemonchosis. Clinical symptoms of haemonchosis is characterised by decreased production, cachexia, and severe anaemia due to worms that sucking blood from the abomasal mucosa. In chronic infections the symptoms shows general oedema. Gross pathological findings are pale mucosa and carcass, hydrothorax, ascites, and haemorrhagic abomasum. Whereas histopathological features shows desquamation of villous abomasum, extensive hemorrhage of abomasal mucosa-submucosa, infiltration of large numbers of eosinophil and mononuclear cells, and cells undergoing degeneration and necrosis of internal organs.  In general, the above exposure will show that haemonchosis usually associated with anaemia, cachexia, oedema, haemorrhage, infiltration of eosinophil and mononuclear cells in the abomasal mucosa.</p>

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