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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 -
Medicina (Kaunas, Lithuania) Jun 2022Background and Objectives: Wound healing is commonly associated with critical bacterial colonization or bacterial infection, which induces prolonged inflammation,...
Background and Objectives: Wound healing is commonly associated with critical bacterial colonization or bacterial infection, which induces prolonged inflammation, resulting in delayed re-epithelialization. An appropriate wound dressing requires a humid environment, which also functions as a barrier against bacterial contamination and will accelerate a regenerative response of the wound. Silver sulfadiazine (SSD) is used to prevent wound infection. Hyaluronic acid (HA) is an extracellular matrix component involved in tissue regeneration. This retrospective study was conducted to evaluate the effectiveness of cream and gauze pads based on hyaluronic acid at low molecular weight (200 kDa) and silver sulfadiazine 1% in the wound healing process. In addition, we examined SSD action on biofilms in vitro and on animal wounds, obtaining positive outcomes therefrom. Materials and Methods: We selected 80 patients with complicated chronic wounds of different etiologies, including diabetes mellitus (10), post-traumatic ulcers (45), burns (15), and superficial abrasion (10). Results: After 8 weeks, ulcer size was decreased in 95 ± 2% of the treated patients; a significant reduction in the inflammatory process was observed from day 14 onwards (p < 0.01 vs. baseline), considering improvement of the surrounding skin and reduction of the bacterial load. The SSD treatment decreased bacterial colony proliferation, both in planktonic state and in biofilm, in a dose-dependent manner on the wound but inhibited the development of tissue granulation at the highest dose (800 μg/wound). Conclusions: In conclusion, the combined action of SSD and HA is clinically effective in improving wound healing.
Topics: Animals; Biofilms; Humans; Hyaluronic Acid; Retrospective Studies; Silver Sulfadiazine; Wound Healing
PubMed: 35744098
DOI: 10.3390/medicina58060835 -
Frontiers in Cellular and Infection... 2022is a zoonotic parasite that infects the brain of humans and causes cerebral toxoplasmosis. The recommended drugs for the treatment or prophylaxis of toxoplasmosis are...
is a zoonotic parasite that infects the brain of humans and causes cerebral toxoplasmosis. The recommended drugs for the treatment or prophylaxis of toxoplasmosis are pyrimethamine (PY) and sulfadiazine (SZ), which have serious side effects. Other drugs available for toxoplasmosis are poorly tolerated. Dihydroquinine (DHQ) is a compound closely related to quinine-based drugs that have been shown to inhibit and in addition to its anti-arrhythmia properties. However, little is known about the effect of DHQ in growth and its mechanism of action . In this study, we report the anti- and anti-invasion properties of DHQ. DHQ significantly inhibited tachyzoite growth with IC values of 0.63, 0.67, and 0.00137 µM at 24, 48, and 72 h, respectively. Under similar conditions, SZ and PY, considered as the gold standard drugs for the treatment of toxoplasmosis, had IC values of 1.29, 1.55, and 0.95 and 3.19, 3.52, and 2.42 µM, respectively. The rapid dose-dependent inhibition of tachyzoites by DHQ compared to the standard drugs (SZ and PY) indicates that DHQ has high selective parasiticidal effects against tachyzoite proliferation. Remarkably, DHQ had an excellent selectivity index (SI) of 149- and 357-fold compared to 24- and 143-fold for PY and SZ, respectively, using fibroblast cells. In addition, DHQ disrupted tachyzoite mitochondrial membrane potential and adenosine triphosphate (ATP) production and elicited high reactive oxygen species (ROS) generation. Taking all these findings together, DHQ promises to be an effective and safe lead for the treatment of toxoplasmosis.
Topics: Antiparasitic Agents; Humans; Quinidine; Sulfadiazine; Toxoplasma; Toxoplasmosis, Cerebral
PubMed: 35646733
DOI: 10.3389/fcimb.2022.852889 -
American Journal of Veterinary Research Apr 2018OBJECTIVE To assess effects of photobiomodulation, silver sulfadiazine, and a topical antimicrobial product for the treatment of experimentally induced full-thickness...
Gross and histologic evaluation of effects of photobiomodulation, silver sulfadiazine, and a topical antimicrobial product on experimentally induced full-thickness skin wounds in green iguanas (Iguana iguana).
OBJECTIVE To assess effects of photobiomodulation, silver sulfadiazine, and a topical antimicrobial product for the treatment of experimentally induced full-thickness skin wounds in green iguanas (Iguana iguana). ANIMALS 16 healthy subadult green iguanas. PROCEDURES Iguanas were anesthetized, and three 5-mm cutaneous biopsy specimens were obtained from each iguana (day 0). Iguanas were randomly assigned to 2 treatment groups, each of which had a control treatment. Wounds in the topical treatment group received silver sulfadiazine, a topical antimicrobial product, or no treatment. Wounds in the laser treatment group received treatment with a class 4 laser at 5 or 10 J/cm or no treatment. Wound measurements were obtained daily for 14 days. Iguanas were euthanized, and treatment sites were evaluated microscopically to detect ulceration, bacterial contamination, reepithelialization, necrosis, inflammation, fibrosis, and collagen maturity. RESULTS On day 14, wounds treated with a laser at 10 J/cm were significantly smaller than those treated with silver sulfadiazine, but there were no other significant differences among treatments. Histologically, there were no significant differences in ulceration, bacterial infection, reepithelialization, necrosis, inflammation, fibrosis, and collagen maturity among treatments. CONCLUSIONS AND CLINICAL RELEVANCE Photobiomodulation at 10 J/cm appeared to be a safe treatment that was tolerated well by green iguanas, but it did not result in substantial improvement in histologic evidence of wound healing, compared with results for other treatments or no treatment.
Topics: Administration, Topical; Animals; Anti-Infective Agents; Bacterial Infections; Iguanas; Low-Level Light Therapy; Silver Sulfadiazine; Wound Healing
PubMed: 29583044
DOI: 10.2460/ajvr.79.4.465 -
British Medical Journal Dec 1975
Review
Topics: Colon; Drug Combinations; Drug Therapy; Endocarditis, Bacterial; Gas Gangrene; Humans; Infant, Newborn; Infant, Newborn, Diseases; Intestinal Diseases; Neutropenia; Nitrofurantoin; Penicillin G; Penicillin G Benzathine; Penicillin G Procaine; Penicillin Resistance; Preanesthetic Medication; Preventive Medicine; Respiratory Tract Infections; Rheumatic Fever; Sulfadiazine; Sulfamerazine; Sulfathiazoles; Surgical Wound Infection; Urinary Tract Infections
PubMed: 1106812
DOI: 10.1136/bmj.4.5996.561 -
Clinical & Experimental Ophthalmology 2013The term, ocular toxoplasmosis, refers to eye disease related to infection with the parasite, Toxoplasma gondii. Recurrent posterior uveitis is the typical form of this... (Review)
Review
The term, ocular toxoplasmosis, refers to eye disease related to infection with the parasite, Toxoplasma gondii. Recurrent posterior uveitis is the typical form of this disease, characterized by unilateral, necrotizing retinitis with secondary choroiditis, occurring adjacent to a pigmented retinochoroidal scar and associated with retinal vasculitis and vitritis. Multiple atypical presentations are also described, and severe inflammation is observed in immunocompromised patients. Histopathological correlations demonstrate focal coagulative retinal necrosis, and early in the course of the disease, this inflammation is based in the inner retina. For typical ocular toxoplasmosis, a diagnosis is easily made on clinical examination. In atypical cases, ocular fluid testing to detect parasite DNA by polymerase chain reaction or to determine intraocular production of specific antibody may be extremely helpful for establishing aetiology. Given the high seroprevalence of toxoplasmosis in most communities, serological testing for T. gondii antibodies is generally not useful. Despite a lack of published evidence for effectiveness of current therapies, most ophthalmologists elect to treat patients with ocular toxoplasmosis that reduces or threatens to impact vision. Classic therapy consists of oral pyrimethamine and sulfadiazine, plus systemic corticosteroid. Substantial toxicity of this drug combination has spurred interest in alternative antimicrobials, as well as local forms of drug delivery. At this time, however, no therapeutic approach is curative of ocular toxoplasmosis.
Topics: Animals; Antiprotozoal Agents; Chorioretinitis; Drug Therapy, Combination; Glucocorticoids; Humans; Pyrimethamine; Sulfadiazine; Toxoplasma; Toxoplasmosis, Ocular
PubMed: 22712598
DOI: 10.1111/j.1442-9071.2012.02838.x -
Molecules (Basel, Switzerland) Jun 2022The α-D-glucopyranoside and its derivatives were as the cardinal investigation for developing an effective medication to treat the highest deadly white spot syndrome...
Investigation of the New Inhibitors by Sulfadiazine and Modified Derivatives of α-D-glucopyranoside for White Spot Syndrome Virus Disease of Shrimp by In Silico: Quantum Calculations, Molecular Docking, ADMET and Molecular Dynamics Study.
The α-D-glucopyranoside and its derivatives were as the cardinal investigation for developing an effective medication to treat the highest deadly white spot syndrome virus (WSSV) diseases in Shrimp. In our forthcoming work, both computational tools, such as molecular docking, quantum calculations, pharmaceutical kinetics, ADMET, and their molecular dynamics, as well as the experimental trial against WSSV, were executed to develop novel inhibitors. In the beginning, molecular docking was carried out to determine inhibitors of the four targeted proteins of WSSV (PDB ID: 2ED6, 2GJ2, 2GJI, and 2EDM), and to determine the binding energies and interactions of ligands and proteins after docking. The range of binding affinity was found to be between -5.40 and -7.00 kcal/mol for the protein 2DEM, from -5.10 to 6.90 kcal/mol for the protein 2GJ2, from -4.70 to -6.2 kcal/mol against 2GJI, and from -5.5 kcal/mol to -6.6 kcal/mol for the evolved protein 2ED6 whereas the L01 and L03 display the highest binding energy in the protein 2EDM. After that, the top-ranked compounds (L01, L02, L03, L04, and L05), based on their high binding energies, were tested for molecular dynamics (MD) simulations of 100 ns to verify the docking validation and stability of the docked complex by calculating the root mean square deviation (RMSD) and root mean square fluctuation (RMSF). The molecules with the highest binding energy were then picked and compared to the standard drugs that were been applied to fish experimentally to evaluate the treatment at various doses. Consequently, approximately 40-45% cure rate was obtained by applying the dose of oxytetracycline (OTC) 50% with vitamin C with the 10.0 g/kg feed for 10 days. These drugs (L09 to L12) have also been executed for molecular docking to compare with α-D-glucopyranoside and its derivatives (L01 to L08). Next, the evaluation of pharmacokinetic parameters, such as drug-likeness and Lipinski's principles; absorption; distribution; metabolism; excretion; and toxicity (ADMET) factors, were employed gradually to further evaluate their suitability as inhibitors. It was discovered that all ligands (L01 to L12) were devoid of hepatotoxicity, and the AMES toxicity excluded L05. Additionally, all of the compounds convey a significant aqueous solubility and cannot permeate the blood-brain barrier. Moreover, quantum calculations based on density functional theory (DFT) provide the most solid evidence and testimony regarding their chemical stability, chemical reactivity, biological relevance, reactive nature and specific part of reactivity. The computational and virtual screenings for in silico study reveals that these chosen compounds (L01 to L08) have conducted the inhibitory effect to convey as a possible medication against the WSSV than existing drugs (L09, L10, L11 and L12) in the market. Next the drugs (L09, L10, L11 and L12) have been used in trials.
Topics: Animals; Ligands; Molecular Docking Simulation; Molecular Dynamics Simulation; Sulfadiazine; White spot syndrome virus 1
PubMed: 35744817
DOI: 10.3390/molecules27123694 -
Ecotoxicology and Environmental Safety Jan 2023Norfloxacin (NFX) and sulfadiazine (SDZ) are two widely used antibiotics belonging to fluoroquinolone and sulfonamide groups, respectively, and have become the commonly...
Norfloxacin (NFX) and sulfadiazine (SDZ) are two widely used antibiotics belonging to fluoroquinolone and sulfonamide groups, respectively, and have become the commonly detected micropollutants in aquatic environments. However, only few works have been conducted to investigate the highly probable inhibition of these antibiotic pollutants to Arthrospira platensis, which is an important species of cyanobacteria that is one of primary producers in aquatic ecosystems and should be remarkably sensitive to environmental pollutants due to its prokaryotic characteristics. Hence, the toxicological effects and removal efficiencies of NFX and SDZ in culturing A. platensis were studied by analyzing the biomass growth, photosynthetic pigments, primary biocomponents, and antibiotics concentration. The corresponding variations of these characteristics showed the higher sensitivity of A. platensis to NFX than to SDZ, indicating the specifically targeted effect of NFX on A. platensis, which could be confirmed in silico by the higher binding affinity of NFX with the critical enzyme. The obtained results illustrated the roles of NFX and SDZ on the growth of A. platensis, thus providing the great support in employing A. platensis to reduce hazards from contaminated water and recover biomass resources.
Topics: Spirulina; Norfloxacin; Sulfadiazine; Ecosystem; Biomass; Anti-Bacterial Agents
PubMed: 36592587
DOI: 10.1016/j.ecoenv.2022.114468 -
Frontiers in Immunology 2022infects one-third of the world population. For decades, it has been considered a silent lifelong infection. However, chronically -infected persons may present...
Sulfadiazine Plus Pyrimethamine Therapy Reversed Multiple Behavioral and Neurocognitive Changes in Long-Term Chronic Toxoplasmosis by Reducing Brain Cyst Load and Inflammation-Related Alterations.
infects one-third of the world population. For decades, it has been considered a silent lifelong infection. However, chronically -infected persons may present psychiatric and neurocognitive changes as anxiety, depression, and memory loss. In a model of long-term chronic infection, behavioral alterations parallel neuroinflammation and systemic high cytokine levels, and may reflect brain cyst load. Recent findings support that in chronic infection an active parasite-host interplay involves an immune-mediated control of tissue cysts. Here, we tested the idea that etiological treatment in chronic phase may add advantage to intrinsic immune-mediated cyst control and impact behavioral changes. Thus, we combined sulfadiazine-plus-pyrimethamine (S+P), the first-choice therapy for toxoplasmosis, to study the association of brain cyst load and biological processes related to the immune response (neuroinflammation, blood-brain barrier -BBB- disruption and serum cytokine levels), with behavioral and neurocognitive changes of long-term chronic infection. Female C57BL/6 mice (H-2) were infected (5 cysts, ME-49 strain) and treated with S+P from 30 to 60 days postinfection (dpi), compared with vehicle (Veh)-treated and noninfected controls. At endpoints (pre-therapy, 30 dpi; S+P therapy, 60 dpi; after ceased therapy, 90 dpi), independent groups were subjected to behavioral tests, and brain tissues and sera were collected. Multiple behavioral and neurocognitive changes were detected in the early (30 dpi) and long-term (60 and 90 dpi) chronic infection. S+P therapy resolved locomotor alterations, anxiety, and depressive-like behavior, partially or transiently ameliorated hyperactivity and habituation memory loss. Analysis after therapy cessation showed that S+P therapy reduced the number of stimuli required for aversive memory consolidation. S+P therapy resulted in reduced brain cyst load, neuroinflammation and BBB disruption, and lowered systemic Th1-cytokine levels. Correlation analysis revealed association between IFNγ, TNF and MCP-1/CCL2 serum levels, brain cyst load and behavioral and neurocognitive alterations. Moreover, principal-component analysis (PCA-2D and 3D projections) highlighted distinction between clusters (noninfected; Veh-treated and S+P-treated infected). Thus, our data suggest that S+P therapy added gain to intrinsic brain cyst control and, direct or indirectly, ameliorated inflammation-related alterations, traits associated with behavioral and neurocognitive alterations.
Topics: Animals; Brain; Cytokines; Female; Inflammation; Memory Disorders; Mice; Mice, Inbred C57BL; Pyrimethamine; Sulfadiazine; Toxoplasmosis
PubMed: 35572567
DOI: 10.3389/fimmu.2022.822567 -
Comparative Medicine Feb 2021With the alarming increase in heart disease and heart failure, the need for appropriate and ethical animal models of cardiac dysfunction continues to grow. Currently,...
With the alarming increase in heart disease and heart failure, the need for appropriate and ethical animal models of cardiac dysfunction continues to grow. Currently, many animal models of cardiomyopathy require either invasive procedures or genetic manipulation, both of which require extensive expertise, time, and cost. Serendipitous findings at our institution revealed a possible correlation between sulfadiazine-trimethoprim (SDZ-TMP) medicated diet and the development of cardiomyopathy in IcrTac:ICR mice. We hypothesized that mice fed SDZ-TMP medicated diet continuously for 3 to 6 mo would develop cardiomyocyte degeneration and fibrosis, eventually leading to dilated cardiomyopathy. A total of 44 mice (22 Hsd:ICR (CD1) and 22 Tac:SW) were enrolled in the study. Half of these 44 mice were fed standard rodent diet and the other half were fed SDZ-TMP medicated diet. Baseline samples, including weights, CBCs, select biochemistry parameters, and echocardiography were performed prior to the start of either diet. Weights were obtained monthly and all other parameters were measured at least once during the study, and again at its conclusion. After 42 wk, mice were euthanized, and heart, lung and bone marrow tissue were submitted for histopathologic evaluation. Histologically, hearts were scored for the degree of degeneration, fibrosis, inflammation, and vacuolation. The data showed that SDZ-TMP did not have a significant effect on cardiac function, RBC parameters, biochemistry parameters (ALT, AST, calcium, magnesium, creatine kinase, and creatinine), hematopoiesis, or histologic heart scores. In addition, mice fed the SDZ-TMP medicated diet gained less weight over time. In summary, we were unable to reproduce the previous findings and thus could not use this approach to develop a novel model of cardiomyopathy. However, these results indicate that SDZ-TMP medicated diet containing 1,365 ppm of SDZ and 275 ppm of TMP does not appear to have long-term detrimental effects in mice.
Topics: Administration, Oral; Animals; Diet; Hematology; Mice; Mice, Inbred ICR; Sulfadiazine; Trimethoprim; Weight Gain
PubMed: 33514448
DOI: 10.30802/AALAS-CM-20-000065