Hemozoin (beta-hematin) formation inhibitors; A promising target for the development of new antimalarials: Current update and A future prospect

2021 ◽  
Vol 25 ◽  
Author(s):  
Suraj N. Mali ◽  
Anima Pandey
Keyword(s):  
Low Income ◽  
Future Prospect ◽  
Food Vacuole ◽  
Malarial Parasite ◽  
Drug Resistant ◽  
Redox Active ◽  
Promising Target ◽  
Free Heme ◽  
Near Future ◽  
Detoxification Process

Background: Malaria is responsible for a social and an economic burden in most low-income malaria-affected countries. Thus, newer antimalarials are needed to tackle morbidities and mortalities associated with the drug-resistant malarial strains. Haemoglobin digestion inside the food vacuole of malarial parasite would lead to producing redox-active and toxic-free heme. The detoxification process adopted by Plasmodium sp. would give rise to hemozoin (Hz) (beta-hematin) formation. Targeting the pathway of hemozoin formation is considered as a validated target for the discovery of newer antimalarials. Objective: This study aims to collect detailed information about aspects of hemozoin (Hz) (beta-hematin) inhibitors. Methods: A systemic search has been carried out using PubMed, Google Scholar, CNKI, etc., for relevant studies having the keyword, ' hemozoin or beta-hematin' for almost the last 2 decades (2000-2021). Results: This mini-review tries to summarize all the recent advancements made for the developments of synthetic, natural isolated phytoconstituents and plant extracts inhibiting the hemozoin (beta-hematin) formation. Conclusion: thus, would act as promising antimalarial candidates in near future.

TREATMENT OF CARBAPENEM RESISTANT ENTEROBACTERIACEAE URINARY TRACT INFECTION WITH COMBINATION OF AMIKACIN AND MEROPENEM

2021 ◽  
pp. 54-55
Author(s):  
Jayesh Kalbhande ◽  
Vicky Kuldeep
Keyword(s):  
Drug Resistance ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
New Drugs ◽  
Resistant Organism ◽  
Drug Resistant ◽  
Carbapenem Resistant ◽  
Multiple Drugs ◽  
Near Future

Drug resistance of bacteria is biggest challenge humanity is going to face in near future. Bacteria are rapidly developing resistant to multiple drugs and there are not many new drugs in pipeline. Infection because of drug resistant organism is a common cause of morbidity and mortality in intensive care unit. If acquisition of drug resistance by microorganism progresses at this rate, that time is not very far when we will be pushed in to preantibiotic era. We need to develop new strategies to combat drug resistant by microorganism. We report a case of highly drug resistant urinary tract infection caused by Klebsiella. This strain was resistant to both Inj. Meropenem and Inj. Amikacin. This case was successfully treated by combination of Inj. Meropenem and Inj. Amikacin and complete resolution of infection was observed.

Hydrazonophenol, a Food Vacuole-Targeted and Ferriprotoporphyrin IX-Interacting Chemotype Prevents Drug-Resistant Malaria

2018 ◽  
Vol 5 (1) ◽  
pp. 63-73
Author(s):  
Shubhra Jyoti Saha ◽  
Asim Azhar Siddiqui ◽  
Saikat Pramanik ◽  
Debanjan Saha ◽  
Rudranil De ◽  
...  
Keyword(s):  
Food Vacuole ◽  
Drug Resistant

scholarly journals Antiplasmodial Activity of [(Aryl)arylsulfanylmethyl]Pyridine

2007 ◽  
Vol 52 (2) ◽  
pp. 705-715 ◽  
Author(s):  
Sanjay Kumar ◽  
Sajal Kumar Das ◽  
Sumanta Dey ◽  
Pallab Maity ◽  
Mithu Guha ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Malaria Parasite ◽  
Spin Trap ◽  
Antimalarial Activity ◽  
Lipid Peroxide ◽  
Food Vacuole ◽  
Mitochondrial Potential ◽  
Free Heme

ABSTRACT A series of [(aryl)arylsufanylmethyl]pyridines (AASMP) have been synthesized. These compounds inhibited hemozoin formation, formed complexes (KD = 12 to 20 μM) with free heme (ferriprotoporphyrin IX) at a pH close to the pH of the parasite food vacuole, and exhibited antimalarial activity in vitro. The inhibition of hemozoin formation may develop oxidative stress in Plasmodium falciparum due to the accumulation of free heme. Interestingly, AASMP developed oxidative stress in the parasite, as evident from the decreased level of glutathione and increased formation of lipid peroxide, H2O2, and hydroxyl radical (·OH) in P. falciparum. AASMP also caused mitochondrial dysfunction by decreasing mitochondrial potential (ΔΨm) in malaria parasite, as measured by both flow cytometry and fluorescence microscopy. Furthermore, the generation of ·OH may be mainly responsible for the antimalarial effect of AASMP since ·OH scavengers such as mannitol, as well as spin trap α-phenyl-n-tertbutylnitrone, significantly protected P. falciparum from AASMP-mediated growth inhibition. Cytotoxicity testing of the active compounds showed selective activity against malaria parasite with selectivity indices greater than 100. AASMP also exhibited profound antimalarial activity in vivo against chloroquine resistant P. yoelii. Thus, AASMP represents a novel class of antimalarial.

scholarly journals Antimalarial Activity of Cupredoxins

2013 ◽  
Vol 288 (29) ◽  
pp. 20896-20907 ◽  
Author(s):  
Isabel Cruz-Gallardo ◽  
Irene Díaz-Moreno ◽  
Antonio Díaz-Quintana ◽  
Antonio Donaire ◽  
Adrián Velázquez-Campoy ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Antimalarial Activity ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Food Vacuole ◽  
Parasite Growth ◽  
Titration Calorimetry ◽  
Erythrocyte Invasion ◽  
Promising Target

The discovery of effective new antimalarial agents is urgently needed. One of the most frequently studied molecules anchored to the parasite surface is the merozoite surface protein-1 (MSP1). At red blood cell invasion MSP1 is proteolytically processed, and the 19-kDa C-terminal fragment (MSP119) remains on the surface and is taken into the red blood cell, where it is transferred to the food vacuole and persists until the end of the intracellular cycle. Because a number of specific antibodies inhibit erythrocyte invasion and parasite growth, MSP119 is therefore a promising target against malaria. Given the structural homology of cupredoxins with the Fab domain of monoclonal antibodies, an approach combining NMR and isothermal titration calorimetry (ITC) measurements with docking calculations based on BiGGER is employed on MSP119-cupredoxin complexes. Among the cupredoxins tested, rusticyanin forms a well defined complex with MSP119 at a site that overlaps with the surface recognized by the inhibitory antibodies. The addition of holo-rusticyanin to infected cells results in parasitemia inhibition, but negligible effects on parasite growth can be observed for apo-rusticyanin and other proteins of the cupredoxin family. These findings point to rusticyanin as an excellent therapeutic tool for malaria treatment and provide valuable information for drug design.

Indicators of candidates for gentrification: a spatial framework

2019 ◽  
Vol 12 (4) ◽  
pp. 736-745
Author(s):  
Ingemar Bengtsson ◽  
Fredrik Kopsch
Keyword(s):  
Low Income ◽  
Design Methodology ◽  
Driving Forces ◽  
Spatial Clustering ◽  
Demographic Variables ◽  
Neighborhood Characteristics ◽  
Content Type ◽  
Spatial Spillovers ◽  
Near Future ◽  
Measurable Factors

Purpose The purpose of this paper is to establish measurable factors that can be used as early indicators of which neighborhoods are most likely to undergo a process of gentrification in a reasonably near future. Design/methodology/approach Using 1990 data on key demographic variables for 128 neighborhoods in Stockholm, Sweden a model that allows both for testing of spatial clustering and for spatial spillovers between neighborhoods is estimated. It is hypothesized not only that gentrification depends on inter-neighborhood characteristics but also that gentrified neighborhoods will cluster and preferably be located in proximity to existing high income neighborhoods. Findings The findings confirm the stated hypotheses. Among the results, it is shown that neighborhoods that gentrified between 1990 and 2012 were more likely to have been poor in 1990 and located closer to the CBD, they were also more likely to be close to neighborhoods with lower proportions of low income residents. It is also found that gentrified neighborhoods tend to cluster over space. Originality/value Much of the previous literature on gentrification has concerned the actual driving forces behind gentrifying neighborhoods. This paper is more concerned with indicators that can be used to spot neighborhoods that are likely to undergo a gentrification process in the future. Such information can be valuable for real estate developers in the private sector, as it may lead to more successful investments. It may also be useful for city developers at the municipal organization.

California Route 91 Toll Lanes Impacts and Other Observations

1998 ◽  
Vol 1649 (1) ◽  
pp. 55-62 ◽  
Author(s):  
Edward C. Sullivan ◽  
Joe el Harake
Keyword(s):  
Low Income ◽  
The United States ◽  
First Year ◽  
Toll Pricing ◽  
Wide Range ◽  
Toll Lanes ◽  
Traffic Composition ◽  
Operational Impacts ◽  
Near Future ◽  
Departments Of Transportation

The 16-km (10-mi) long California State Route 91 (SR-91) variable-toll lanes entered service December 27, 1995. This facility is the first practical application of congestion-based road pricing attempted in the United States. The California and U.S. Departments of Transportation sponsored a study to observe how travelers respond over time to variable-toll pricing and the other innovative features of this unique facility. Data covering a wide range of travel and transportation issues were obtained from mid-1994 through June 1997 and analyzed for lessons to inform public policies about future applications of congestion-based pricing. The principal findings are summarized. The SR-91 toll lanes are regarded as a success in terms of both commuter acceptance and favorable opinions. Although, as expected, first-year toll revenues did not cover total annualized costs, the facility operator anticipates profitability in the near future. Impacts on corridor traffic have been positive, and, despite changes in traffic composition, the overall level of ridesharing has not been adversely affected. Fears that peak congestion-based tolls might preclude benefits to low-income commuters have not materialized, although a relationship was found between frequency of toll lane use and income level. No adverse traffic operational impacts were observed. From experience with the SR-91 variable-toll lanes, further careful experimentation with congestion-based pricing in other settings appears warranted.

scholarly journals Antimalarials increase vesicle pH in Plasmodium falciparum.

1985 ◽  
Vol 101 (6) ◽  
pp. 2302-2309 ◽  
Author(s):  
D J Krogstad ◽  
P H Schlesinger ◽  
I Y Gluzman
Keyword(s):  
Plasmodium Falciparum ◽  
Mammalian Cells ◽  
Human Fibroblasts ◽  
Food Vacuole ◽  
Malarial Parasite ◽  
Red Cell ◽  
Trophozoite Stage ◽  
Weak Bases ◽  
Erythrocytic Cycle ◽  
Initial Ph

The asexual erythrocytic stage of the malarial parasite ingests and degrades the hemoglobin of its host red cell. To study this process, we labeled the cytoplasm of uninfected red cells with fluorescein-dextran, infected those cells with trophozoite- and schizont-rich cultures of Plasmodium falciparum, and harvested them 110-120 h later in the trophozoite stage. After lysis of the red cell cytoplasm with digitonin, the only fluorescence remaining was in small (0.5-0.9 micron) vesicles similar to the parasite's food vacuole. As measured by spectrofluorimetry, the pH of these vesicles was acid (initial pH 5.2-5.4), and they responded to MgATP with acidification and to weak bases such as NH4Cl with alkalinization. These three properties are similar to those obtained with human fibroblasts and suggest that the endocytic vesicles of plasmodia are similar to those of mammalian cells. Each of the antimalarials tested (chloroquine, quinine, and mefloquine) as well as NH4Cl inhibited parasite growth at concentrations virtually identical to those that increased parasite vesicle pH. These results suggest two conclusions: (a) The increases in vesicle pH that we have observed in our digitonin-treated parasite preparation occur at similar concentrations of weak bases and antimalarials in cultures of parasitized erythrocytes, and (b) P. falciparum parasites are exquisitely dependent on vesicle pH during their asexual erythrocytic cycle, perhaps for processes analogous to endocytosis and proteolysis in mammalian cells, and that antimalarials and NH4Cl may act by interfering with these events.

scholarly journals The burden of drug resistant tuberculosis in a predominantly nomadic population in Uganda: a mixed methods study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Brenda Nakafeero Simbwa ◽  
Achilles Katamba ◽  
Elizabeth B. Katana ◽  
Eva A. O. Laker ◽  
Sandra Nabatanzi ◽  
...  
Keyword(s):  
Mixed Methods ◽  
Low Income ◽  
Conditional Logistic Regression ◽  
Drug Resistant ◽  
Cross Sectional ◽  
Drug Resistant Tuberculosis ◽  
Public Health Burden ◽  
Factors Associated ◽  
Tb Treatment ◽  
Resistant Tuberculosis

Abstract Background Emergence of drug resistant tuberculosis (DR-TB) has aggravated the tuberculosis (TB) public health burden worldwide and especially in low income settings. We present findings from a predominantly nomadic population in Karamoja, Uganda with a high-TB burden (3500 new cases annually) and sought to determine the prevalence, patterns, factors associated with DR-TB. Methods We used mixed methods of data collection. We enrolled 6890 participants who were treated for tuberculosis in a programmatic setting between January 2015 and April 2018. A cross sectional study and a matched case control study with conditional logistic regression and robust standard errors respectively were used to the determine prevalence and factors associated with DR-TB. The qualitative methods included focus group discussions, in-depth interviews and key informant interviews. Results The overall prevalence of DR-TB was 41/6890 (0.6%) with 4/64,197 (0.1%) among the new and 37/2693 (1.4%) among the previously treated TB patients respectively. The drug resistance patterns observed in the region were mainly rifampicin mono resistant (68.3%) and Multi Drug-Resistant Tuberculosis (31.7%). Factors independently associated with DR-TB were previous TB treatment, adjusted odds ratio (aOR) 13.070 (95%CI 1.552–110.135) and drug stock-outs aOR 0.027 (95%CI 0.002–0.364). The nomadic lifestyle, substance use, congested homesteads and poor health worker attitudes were a great challenge to effective treatment of TB. Conclusion Despite having the highest national TB incidence, Karamoja still has a low DR-TB prevalence. Previous TB treatment and drug stock outs were associated with DR-TB. Regular supply of anti TB medications and health education may help to stem the burden of TB disease in this nomadic population.

The COVID-19 Pandemic: Key Factors in Canada’s Social Policy Development

2021 ◽  
pp. 73
Author(s):  
Maria Solyanova
Keyword(s):  
Low Income ◽  
Policy Development ◽  
Social Protection ◽  
Vulnerable Groups ◽  
Social Dimensions ◽  
Key Factors ◽  
Skilled Workers ◽  
Low Income Families ◽  
The Government ◽  
Near Future

Many studies focus on the COVID-19 pandemic, response mechanisms and response design. At the same time, it becomes more and more obvious that not only the study of economic policy and decisions made by the government in connection with the pandemic is acquiring relevance. As the spread of the disease continues, social problems and difficulties that political elites will have to deal with are exposed in Canadian society. Despite the fact that the government has taken unprecedented measures to expand assistance and social protection to the most vulnerable groups – low-income families, women, senior citizens, young people and children, low-skilled workers, self-employed, people with disabilities, etc. – the pandemic, however, has had a profound impact on society. The government will be forced to adapt its policies in the field of social protection and labor relations, in the field of health and education. This article seeks to explore the key social dimensions of the COVID-19 pandemic, as well as factors that can influence the political decisions of the Canadian elite in the near future.

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