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Cells Apr 2020Rheumatoid arthritis (RA) is an autoimmune disease that involves multiple joints bilaterally. It is characterized by an inflammation of the tendon (tenosynovitis)... (Review)
Review
Rheumatoid arthritis (RA) is an autoimmune disease that involves multiple joints bilaterally. It is characterized by an inflammation of the tendon (tenosynovitis) resulting in both cartilage destruction and bone erosion. While until the 1990s RA frequently resulted in disability, inability to work, and increased mortality, newer treatment options have made RA a manageable disease. Here, great progress has been made in the development of disease-modifying anti-rheumatic drugs (DMARDs) which target inflammation and thereby prevent further joint damage. The available DMARDs are subdivided into (1) conventional synthetic DMARDs (methotrexate, hydrochloroquine, and sulfadiazine), (2) targeted synthetic DMARDs (pan-JAK- and JAK1/2-inhibitors), and (3) biologic DMARDs (tumor necrosis factor (TNF)-α inhibitors, TNF-receptor (R) inhibitors, IL-6 inhibitors, IL-6R inhibitors, B cell depleting antibodies, and inhibitors of co-stimulatory molecules). While DMARDs have repeatedly demonstrated the potential to greatly improve disease symptoms and prevent disease progression in RA patients, they are associated with considerable side-effects and high financial costs. This review summarizes our current understanding of the underlying pathomechanism, diagnosis of RA, as well as the mode of action, clinical benefits, and side-effects of the currently available DMARDs.
Topics: Animals; Antibodies; Antirheumatic Agents; Arthritis, Rheumatoid; Cytokines; Humans; Inflammation; Models, Biological
PubMed: 32260219
DOI: 10.3390/cells9040880 -
Cureus Mar 2023Wound healing poses a variety of challenges making it a vital subject in medicine. With the advancement of science, we have seen the use of a new xenograft known as... (Review)
Review
Wound healing poses a variety of challenges making it a vital subject in medicine. With the advancement of science, we have seen the use of a new xenograft known as acellular fish skin (AFS) grafts that are derived from either Atlantic cod or Nile Tilapia. Fish skin has shown anti-inflammatory and anti-bacterial properties that support and improve wound healing in a variety of wounds including burns and diabetic foot ulcers (DFU). There is ongoing research that evaluates the efficacy of fish skin grafts in comparison to alternative wound healing techniques. A literature search was conducted through the National Library of Medicine with search terms fish skin graft, AFS, xenograft, dehydrated human amnion/chorion, ulcer, burns, and wounds. A total of ten studies that investigate the efficacy of fish skin grafts either in comparison to a different wound healing technique or by simply observing wound healing with fish skin grafts and recording the results were chosen. AFS showed superior healing in comparison to collagen alginate dressings, silver sulfadiazine cream 1%, and allografts. Although there is no one specific gold standard technique for wound healing, fish skin grafts demonstrated overall improved and quicker wound healing, fewer dressing changes, less pain, and lower costs.
PubMed: 37082504
DOI: 10.7759/cureus.36348 -
Frontiers in Immunology 2021Tuberculosis (TB) is an infectious disease caused by an obligate intracellular pathogen, and is responsible for the maximum number of deaths due to a single... (Review)
Review
Tuberculosis (TB) is an infectious disease caused by an obligate intracellular pathogen, and is responsible for the maximum number of deaths due to a single infectious agent. Current therapy for TB, Directly Observed Treatment Short-course (DOTS) comprises multiple antibiotics administered in combination for 6 months, which eliminates the bacteria and prevents the emergence of drug-resistance in patients if followed as prescribed. However, due to various limitations viz., severe toxicity, low efficacy and long duration; patients struggle to comply with the prescribed therapy, which leads to the development of drug resistance (DR). The emergence of resistance to various front-line anti-TB drugs urgently require the introduction of new TB drugs, to cure DR patients and to shorten the treatment course for both drug-susceptible and resistant populations of bacteria. However, the development of a novel drug regimen involving 2-3 new and effective drugs will require approximately 20-30 years and huge expenditure, as seen during the discovery of bedaquiline and delamanid. These limitations make the field of drug-repurposing indispensable and repurposing of pre-existing drugs licensed for other diseases has tremendous scope in anti-DR-TB therapy. These repurposed drugs target multiple pathways, thus reducing the risk of development of drug resistance. In this review, we have discussed some of the repurposed drugs that have shown very promising results against TB. The list includes sulfonamides, sulfanilamide, sulfadiazine, clofazimine, linezolid, amoxicillin/clavulanic acid, carbapenems, metformin, verapamil, fluoroquinolones, statins and NSAIDs and their mechanism of action with special emphasis on their immunomodulatory effects on the host to attain both host-directed and pathogen-targeted therapy. We have also focused on the studies involving the synergistic effect of these drugs with existing TB drugs in order to translate their potential as adjunct therapies against TB.
Topics: Antitubercular Agents; Drug Repositioning; Humans; Immunologic Factors; Immunomodulation; Mycobacterium tuberculosis; Tuberculosis
PubMed: 33927718
DOI: 10.3389/fimmu.2021.645485 -
Wounds : a Compendium of Clinical... Feb 2020Radiation therapy (RT) following breast-conserving surgical excision of cancer reduces cancer-related mortality and recurrence.1 However, most patients experience acute...
Radiation therapy (RT) following breast-conserving surgical excision of cancer reduces cancer-related mortality and recurrence.1 However, most patients experience acute radiation dermatitis (ARD) within weeks after beginning RT2; symptoms of ARD, including severe skin erythema, dryness, moist or dry desquamation, and/or ulceration, may interrupt radiotherapy. This can negatively affect patient quality of life (QoL) and cancer outcomes. Acute radiation dermatitis is not to be confused with chronic radiation dermatitis, which can lead to fibrosis, skin atrophy, pigmentation, and telangiectasia months to years after RT.3 Evidence-based guidelines4 to both prevent and treat ARD recommend the application of 1 of 2 topical interventions during and/or after RT: (1) corticosteroids to improve ARD-related discomfort and itching5 or (2) 1% silver sulfadiazine (SSD) cream to reduce ARD-related dermatitis scores.6 This Evidence Corner reviews evidence supporting the 2 aforementioned topical interventions for patients undergoing RT for breast cancer.
Topics: Adrenal Cortex Hormones; Dermatologic Agents; Humans; Radiodermatitis; Silver Sulfadiazine
PubMed: 32155122
DOI: No ID Found -
The disposition of trimethoprim and sulfadiazine in neonatal foals after intravenous administration.Veterinary Medicine and Science May 2022Septicaemia in the neonatal foal is caused by both Gram positive and Gram negative bacteria. The life-threatening nature of this condition requires treatment to be...
BACKGROUND
Septicaemia in the neonatal foal is caused by both Gram positive and Gram negative bacteria. The life-threatening nature of this condition requires treatment to be initiated with broad spectrum antimicrobial drugs pending antimicrobial susceptibility testing. Potentiated sulphonamides, for example, trimethoprim combined with sulfadiazine, could be clinically relevant options but their pharmacokinetics in the neonatal foal are unknown.
OBJECTIVES
To describe the plasma disposition of trimethoprim and sulfadiazine in neonatal foals and to relate the results to patterns in the minimum inhibitory concentration (MIC) for Escherichia coli, a recognized pathogen in neonatal foal sepsis.
METHOD
A total of five doses of trimethoprim (2.5 mg/kg) and sulfadiazine (12.5 mg/kg) were administered intravenously every 12 h to eight neonatal foals that were 3 days old at inclusion. A non-linear mixed effects model was fitted to the trimethoprim and sulfadiazine experimental data. The 24 h area under the free plasma trimethoprim and sulfadiazine concentration-time curves (fAUC) and the pharmacokinetic/pharmacodynamik (PK/PD)-index fAUC/MIC was calculated to evaluate the potential clinical benefits of the administered dose.
RESULTS
For trimethoprim, the typical values were 1.99 L/kg, 0.33 L/h·kg and 4.2 h for the apparent volume of distribution, clearance and terminal half-life, respectively. The 24 h fAUC for trimethoprim was 11.3 μg·h/ml (7.2-15.2) and the fAUC/MIC ratio for E. coli was 23 (16.4-29.2) (population mean (range)). For sulfadiazine, the typical values were 0.61 L/kg, 0.09 L/h·kg and 5.3 h for the apparent volume of distribution, clearance and terminal half-life, respectively. The 24 h fAUC for sulfadiazine was 246.8 μg·h/ml (175.6-335.4).
CONCLUSION
For trimethoprim, the plasma exposure is insufficient in some foals to successfully treat bacterial infections with an MIC-value of 0.5 μg/ml using the studied dosing regimen.
Topics: Administration, Intravenous; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Escherichia coli; Gram-Negative Bacteria; Gram-Positive Bacteria; Horses; Sulfadiazine; Trimethoprim
PubMed: 35152563
DOI: 10.1002/vms3.763 -
Wounds : a Compendium of Clinical... Aug 2019Cutaneous burns challenge global health care systems with high patient morbidity and mortality rates.1 One recent study of adults admitted for 2 to 60 days to a US burn...
Cutaneous burns challenge global health care systems with high patient morbidity and mortality rates.1 One recent study of adults admitted for 2 to 60 days to a US burn center reported that more than 7.9% of burn patients experienced at least 1 hospital-acquired infection (HAI), extending the hospital length of stay and increasing the likelihood of complications and death.2 Of these HAIs, most (35.8%) were skin and soft tissue infections, followed by respiratory (24.4%), bloodstream (18.1%), and urinary tract (17.8%) infections. A burn covering more than 5% of total body surface area (TBSA) multiplied HAI risk by 3, with higher risk as the burned TBSA increased. Other factors increasing HAI risk included inhalation injury, flame burn, patient age (≥ 60 years), and comorbidities (ie, diabetes, heart failure, myocardial infarction, renal disease, or peripheral arterial disease).2 Topical 1% silver sulfadiazine cream (SSD), introduced into burn care in the mid 20th century by Dr. Charles Fox, improved global burned patient survival rates and outcomes by reducing the likelihood of burn-related infection.3 Research in later decades explored other topical treatments capable of reducing the incidence of burn-related infections. This month's Evidence Corner describes 2 recent reviews comparing the effects of topical antiseptics4 or honey5 with SSD on burn wound healing and infections.
PubMed: 31356177
DOI: No ID Found -
Environmental Research Nov 2022In view of the environmental issues caused by antibiotics, this research studies competitive adsorption/desorption for tetracycline (TC) and sulfadiazine (SDZ) in...
In view of the environmental issues caused by antibiotics, this research studies competitive adsorption/desorption for tetracycline (TC) and sulfadiazine (SDZ) in agricultural soils. Competitive adsorption was studied in binary systems (adding equal concentrations of both antibiotics). In addition, it was compared with results from simple systems. In all cases, batch-type adsorption/desorption experiments were carried out. In the binary systems, for the highest antibiotic concentration added, adsorption percentages were always higher for TC (close to 100%) than for SDZ (10-90%). In these systems, TC desorption was lower than 5% for all soils, and generally <10% for SDZ. Comparing TC and SDZ adsorption for the different systems, SDZ was clearly affected by the presence of TC, with SDZ adsorption percentages being was much higher (with differences generally above 65%) in the binary than in the simple systems. On the contrary, comparing the results of TC adsorption in simple and binary systems, TC was not affected by the presence of SDZ, obtaining similar adsorption percentages in both systems. K and K values (in the Linear and Freundlich models), were higher in the simple systems in the case of TC, which could be due to competition with SDZ, while for SDZ K and K were higher in the binary systems, with a synergistic effect of TC favoring SDZ adsorption. Regarding desorption, it reached 100% for SDZ in some soils in simple systems, dropping to 10% in the presence of TC. TC desorption was <4%, not affected by SDZ. The results indicate that environmental risks would be higher for SDZ, showing differences when both antibiotics are present. This can be considered relevant as regards public health and environmental preservation, in view of direct toxicities and the promotion of resistance to antibiotics associated with the presence of these contaminants in the environment.
Topics: Adsorption; Anti-Bacterial Agents; Soil; Soil Pollutants; Sulfadiazine; Tetracycline
PubMed: 35750125
DOI: 10.1016/j.envres.2022.113726