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International Journal of Molecular... Apr 2024The mission of this review is to identify immune-damaging participants involved in antiviral immunoinflammatory lesions. We argue these could be targeted and their... (Review)
Review
The mission of this review is to identify immune-damaging participants involved in antiviral immunoinflammatory lesions. We argue these could be targeted and their activity changed selectively by maneuvers that, at the same time, may not diminish the impact of components that help resolve lesions. Ideally, we need to identify therapeutic approaches that can reverse ongoing lesions that lack unwanted side effects and are affordable to use. By understanding the delicate balance between immune responses that cause tissue damage and those that aid in resolution, novel strategies can be developed to target detrimental immune components while preserving the beneficial ones. Some strategies involve rebalancing the participation of immune components using various approaches, such as removing or blocking proinflammatory T cell products, expanding regulatory cells, restoring lost protective cell function, using monoclonal antibodies (moAb) to counteract inhibitory molecules, and exploiting metabolic differences between inflammatory and immuno-protective responses. These strategies can help reverse ongoing viral infections. We explain various approaches, from model studies and some clinical evidence, that achieve innate and adaptive immune rebalancing, offering insights into potential applications for controlling chronic viral-induced lesions.
Topics: Humans; Antibodies, Monoclonal; Pyrimethamine; Sulfadiazine
PubMed: 38612744
DOI: 10.3390/ijms25073935 -
JAMA Health Forum Oct 2023
Topics: Controlled Substances; Sulfadiazine; Telemedicine
PubMed: 37862032
DOI: 10.1001/jamahealthforum.2023.3251 -
Frontiers in Immunology 2023In this review, we discuss a variety of immune modulating approaches that could be used to counteract tissue-damaging viral immunoinflammatory lesions which typify many... (Review)
Review
In this review, we discuss a variety of immune modulating approaches that could be used to counteract tissue-damaging viral immunoinflammatory lesions which typify many chronic viral infections. We make the point that in several viral infections the lesions can be largely the result of one or more aspects of the host response mediating the cell and tissue damage rather than the virus itself being directly responsible. However, within the reactive inflammatory lesions along with the pro-inflammatory participants there are also other aspects of the host response that may be acting to constrain the activity of the damaging components and are contributing to resolution. This scenario should provide the prospect of rebalancing the contributions of different host responses and hence diminish or even fully control the virus-induced lesions. We identify several aspects of the host reactions that influence the pattern of immune responsiveness and describe approaches that have been used successfully, mainly in model systems, to modulate the activity of damaging participants and which has led to lesion control. We emphasize examples where such therapies are, or could be, translated for practical use in the clinic to control inflammatory lesions caused by viral infections.
Topics: Humans; Models, Biological; Pyrimethamine; Sulfadiazine
PubMed: 37671156
DOI: 10.3389/fimmu.2023.1257192 -
EMBO Molecular Medicine Nov 2023Snyder-Robinson syndrome (SRS) is a rare genetic disorder characterized by intellectual disability and delayed development beginning early in childhood. It was first...
Snyder-Robinson syndrome (SRS) is a rare genetic disorder characterized by intellectual disability and delayed development beginning early in childhood. It was first described in a single family in 1969 as a sex-linked disorder (Snyder & Robinson, 1969) and has since been only identified in less than 100 individuals worldwide. Inherited in an X-linked recessive pattern, SRS has only been identified in males thus far. Snyder-Robinson syndrome primarily affects the nervous system and skeletal tissues and is caused by loss-of-function mutations in the gene encoding spermine synthase (SMS), a polyamine biosynthesis enzyme. Affected males display a collection of clinical features including intellectual disability ranging from mild to profound, speech and vision impairment, osteoporosis, hypotonia, and increasing loss of muscle tissue with age, kyphoscoliosis, seizures, and distinctive facial features including a prominent lower lip and facial asymmetry. Currently, there is no cure or treatment for this debilitating disorder aside from symptom management.
Topics: Male; Humans; Polyamines; Intellectual Disability; Mental Retardation, X-Linked; Mutation; Sulfadiazine
PubMed: 37712293
DOI: 10.15252/emmm.202318506 -
Water Research Jul 2023There has been a significant increase in antimicrobial agents (AAs) usage, globally - however the relative consumption is unevenly distributed between nations.... (Review)
Review
There has been a significant increase in antimicrobial agents (AAs) usage, globally - however the relative consumption is unevenly distributed between nations. Inappropriate use of antibiotics can harbour inherent antimicrobial resistance (AMR); therefore, it is important to understand and monitor community-wide prescribing and consumption behaviours throughout different communities around the world. Wastewater-Based Epidemiology (WBE) is a novel tool enabling low cost and large scale studies focussed on AA usage patterns. The back-calculation of community antimicrobial intake was performed from quantities measured in municipal wastewater and informal settlement discharge in the city of Stellenbosch, utilising WBE. Seventeen antimicrobials, and their human metabolites, were evaluated, in concordance with prescription records corresponding to the catchment region. The proportional excretion, biological/chemical stability, and method recovery of each analyte were all crucial factors in the efficacy of the calculation. Mass per day measurements were normalised to the catchment area via population estimates. Municipal wastewater treatment plant population estimates were used to normalise the wastewater samples and prescription data (mg/day/1000 inhabitants). Population estimates for the informal settlements were less accurate due to a lack of reliable sources that were relevant to the sampling time period. Both mass loads and normalised loads suggested higher than average usage throughout the settlements, relative to municipal wastewater. This was seen most prominently in emtricitabine and lamivudine; but also, sulfamethoxazole, trimethoprim, sulfadiazine, clindamycin, ciprofloxacin, ofloxacin, and doxycycline. Urban water fingerprinting (UWF) data triangulation with prescription datasets showed good correlations for several antimicrobial agents (AAs) (e.g., clindamycin, clarithromycin, ofloxacin, and doxycycline). It also revealed discrepancies in usage for some compounds (e.g., tetracycline and sulfapyridine). This might be linked with a lack of pharma compliance in prescription datasets; erroneous association of prescription boundaries with the sewerage catchment; and/or uncertainties within the sewerage catchment (e.g., population estimations). The UWF tool provided a comprehensive overview of multiclass AAs usage, both prescription and over-the counter. For example, tetracycline was not reported in available prescription statistics, but was detected at an average of 18.4 mg/day/1000inh; and no antiviral prescriptions were obtained, but emtricitabine and lamivudine were quantified at 2415.4 and 144.4 mg/day/1000inh, respectively. A lack of clarity regarding prescriptions and a lack of inclusion of several critical (often over-the-counter) medications in public health databases makes WBE a useful and comprehensive epidemiology tool for tracking pharma usage within a catchment.
Topics: Humans; Anti-Bacterial Agents; Wastewater; Clindamycin; Doxycycline; South Africa; Lamivudine; Ofloxacin; Water Pollutants, Chemical
PubMed: 37247434
DOI: 10.1016/j.watres.2023.120110 -
Animals : An Open Access Journal From... Jul 2023Antibiotics are present in the environment, primarily due to their release through wastewater treatment plants, agricultural practices, and improper disposal of unused...
Antibiotics are present in the environment, primarily due to their release through wastewater treatment plants, agricultural practices, and improper disposal of unused medications. In the environment, these drugs can be bioaccumulated by organisms and transferred along the food chain. This is a problem when considering the consumption of fish meat. In the United States, legislation stipulates that the maximum residue limit for sulfadiazine (SDZ) should not exceed 100 μg kg. Lambari fishes have potential economic importance in aquaculture, as they are relatively easy to breed and can be raised in small-scale operations. Finally, studying the biology and ecology of lambari could provide valuable information about freshwater ecosystems and their inhabitants. The current work aimed to measure the bioaccumulation and depletion of the antibiotic SDZ C in lambari (). For this purpose, the tests were divided into two stages; seven days of exposure and seven days of depletion, where one fish was randomly selected and sampled every day. In the exposure phase, the fish were fed the medicated feed three times a day at a concentration of 2.5 mg·g. The control fish were fed uncontaminated feed. For the depletion phase, the remaining lambari were transferred to clean tanks and fed uncontaminated feed three times a day. The fish samples were burned in the Oxidizer and the reading of radioactivity was performed in a liquid scintillation spectrometer. It is worth noting that on day 7 and day 14, the water in the aquariums was filtered through filter paper to collect the metabolic excrement. SDZ concentrations increased over the days and accumulation occurred in the fish, with day seven presenting the maximum accumulation value of 91.7 ng·g due to feeding uptake. After the depletion phase on day 13, the value found was 0.83 ng·g. The bioconcentration factor calculated was 20 L·kg. After the bioaccumulation period, the concentrations of SDZ in the water and excreta were 4.5 µg·L and 363.5 ng·g, respectively. In the depletion period, the concentrations in the water and excreta were 0.01 µg·L and 5.96 ng·g, respectively. These results imply that there was little SDZ bioaccumulation in the fish, but that it was distributed in larger amounts in the water. This is due to the physicochemical properties of the molecule with the low Log P value. Regarding the maximum residue limit, the value was below the established value. This study contributes to understanding SDZ dynamics in an aquatic species native to Brazil.
PubMed: 37570273
DOI: 10.3390/ani13152464 -
Tropical Medicine and Infectious Disease Aug 2023is deemed a successful parasite worldwide with a wide range of hosts. Currently, a combination of pyrimethamine and sulfadiazine serves as the first-line treatment;...
is deemed a successful parasite worldwide with a wide range of hosts. Currently, a combination of pyrimethamine and sulfadiazine serves as the first-line treatment; however, these drugs have serious adverse effects. Therefore, it is imperative to focus on new therapies that produce the desired effect with the lowest possible dose. The designation and synthesis of sulfonamide-1,2,3-triazole hybrids () were performed to create hybrid frameworks. The newly synthesized compounds were loaded on chitosan nanoparticles (CNPs) to form nanoformulations (, , ) for further in vitro investigation as an anti- treatment. The current study demonstrated that all examined compounds were active against in vitro relative to the control drug, sulfadiazine. showed the best impact against with the lowest IC value of 3.64 µg/mL. Using light microscopy, it was found that Vero cells treated with the three nanoformulae showed remarkable morphological improvement, and tachyzoites were rarely seen in the treated cells. Moreover, scanning and transmission electron microscopic studies confirmed the efficacy of the prepared nanoformulae on the parasites. All of them caused parasite ultrastructural damage and altered morphology, suggesting a cytopathic effect and hence confirming their promising anti- activity.
PubMed: 37624339
DOI: 10.3390/tropicalmed8080401