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ImportanceConcern about the renal effects of nonsteroidand al anti-inflammatory drugs (NSAIDs) among young, healthy adults has been limited, but more attention may be warranted given the prevalent use of these agents.ObjectiveTo t...
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ImportanceConcern about the renal effects of nonsteroidand al anti-inflammatory drugs (NSAIDs) among young, healthy adults has been limited, but more attention may be warranted given the prevalent use of these agents.ObjectiveTo test for associations between dispensed NSAIDs and incident acute kidney injury and chronic kidney disease while controlling for other risk factors.Design, Setting, and ParticipantsThis retrospective, longitudinal cohort study used deidentified medical and administrative data on 764?228 active-duty US Army soldiers serving between January 1, 2011, and December 31, 2014. Analysis was conducted from August 1 to November 30, 2018. All individuals new to Army service were included in the analysis. Persons already serving in January 2011 were required to have at least 7 months of observable time to eliminate those with kidney disease histories.ExposuresMean total defined daily doses of prescribed NSAIDs dispensed per month in the prior 6 months.Main Outcomes and MeasuresIncident outcomes were defined by diagnoses documented in health records and a military-specific digital system.ResultsAmong the 764?228 participants (655 392 [85.8%] men; mean [SD] age, 28.6 [7.9] years; median age, 27.0 years [interquartile range, 22.0-33.0 years]), 502?527 (65.8%) were not dispensed prescription NSAIDs in the prior 6 months, 137 108 (17.9%) were dispensed 1 to 7 mean total defined daily doses per month, and 124?594 (16.3%) received more than 7 defined daily doses per month. There were 2356 acute kidney injury outcomes (0.3% of participants) and 1634 chronic kidney disease outcomes (0.2%) observed. Compared with participants who received no medication, the highest exposure level was associated with significantly higher adjusted hazard ratios (aHRs) for acute kidney injury (aHR, 1.2; 95% CI, 1.1-1.4) and chronic kidney disease (aHR, 1.2; 95% CI, 1.0-1.3), with annual outcome excesses per 100?000 exposed individuals totaling 17.6 cases for acute kidney injury and 30.0 cases for chronic kidney disease.Conclusions and RelevanceModest but statistically significant associations were noted between the highest observed doses of NSAID exposure and incident kidney problems among active young and middle-aged adults.
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Introduction: Benzoxaborole is a versatile boron-heterocyclic scaffold which has found in the last 10 years a broad spectrum of applications in medicinal chemistry, due to its physicochemical and drug-like properties. Use of benzo...
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Introduction: Benzoxaborole is a versatile boron-heterocyclic scaffold which has found in the last 10 years a broad spectrum of applications in medicinal chemistry, due to its physicochemical and drug-like properties. Use of benzoxaborole moiety in the design of compounds led to the discovery of new classes of anti-bacterial, anti-fungal, anti-protozoal, anti-viral as well as anti-inflammatory agents with interesting drug development perspectives.
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In the previous study, we isolated Bacillus coagulans IDCC 1201 from green malt and found that it was safe for use as a probiotic, based on phenotypic and genomic analysis. In the present study, we investigated the anti-inflammato...
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In the previous study, we isolated Bacillus coagulans IDCC 1201 from green malt and found that it was safe for use as a probiotic, based on phenotypic and genomic analysis. In the present study, we investigated the anti-inflammatory and antibacterial activity using the cell-free lysate of this strain since the two properties can be its additional advantages as a probiotic. The following results were obtained: 1) In the RAW 264.7 (a mouse macrophage cell line) treated with lipopolysaccharide, the lysate of this strain inhibited the decrease of cell viability, the increased production of nitric oxide (NO) and prostaglandin E2 (PGE2) and the increased expressions of inducible NO synthase (iNOS) (a NO producer), inducible cyclooxygenase-2 (a PGE2 producer) and proinflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1β, IL-6. 2) The lysate also inhibited the growth of five pathogens such as Staphylococcus aureus, Enterococcus faecalis, Bacillus cereus, Salmonella Typhimurium, and Streptococcus pneumoniae. These two properties obtained provide B. coagulans IDCC 1201 with merits for a probiotic that can be of help particularly to the bowel in the inflammatory condition. Thus, it is thought to be worth developing this strain as a health supplement for this purpose.
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Background: Collinin is a secondary plant metabolite belonging to the class of geranyloxycoumarins. We explored the potential beneficial impact of collinin on periodontal health by investigating its effect on Porphyromonas gingiva...
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Background: Collinin is a secondary plant metabolite belonging to the class of geranyloxycoumarins. We explored the potential beneficial impact of collinin on periodontal health by investigating its effect on Porphyromonas gingivalis (P. gingivalis), lipopolysaccharide (LPS)-induced inflammatory response of macrophages, and osteoclastogenesis. Methods: Collinin was synthesized from pyrogallol and propiolic acid. A microdilution assay was used to determine antibacterial activity of collinin. The effect of collinin on collagenase activity of P. gingivalis was determined using fluorescent collagen. Macrophages were treated with collinin before being stimulated with LPS. The secretion of interleukin-6, chemokine (C-C motif) ligand 5, and prostaglandin E2 was assessed by enzyme-linked immunosorbent assays (ELISA). The inhibitory effect of collinin on differentiation of human preosteoclastic cells was assessed by tartrate-resistant acid phosphatase staining, whereas the secretion of matrix metalloproteinase-9 (MMP-9) was measured by ELISA. Bone resorption activity was investigated by using a human bone plate coupled with an immunoassay that detected the release of collagen fragments. Results: Collinin inhibited the growth of P. gingivalis. The effect was more pronounced under ironrestricted conditions. Collinin dose dependently inhibited the degradation of type I collagen by P. gingivalis. It was also a potent inhibitor of the LPS-induced inflammatory response in macrophages and completely inhibited receptor activator of nuclear factor kB ligand-dependent osteoclast differentiation and MMP-9 secretion. Last, collinin affected bone degradation mediated by mature osteoclasts by significantly decreasing the release of collagen helical peptides. Conclusion: Although clinical trials are required, data from these in vitro analyses support the potential of collinin as a therapeutic agent for treating inflammatory periodontitis associated with bone breakdown.
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OBJECTIVES: Variation in medical care can be a barrier to improving clinical outcomes. We aim to describe the variation in care of Crohn disease as provided by a broad sample of pediatric gastroenterologists. METHODS: Two hundred ...
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OBJECTIVES: Variation in medical care can be a barrier to improving clinical outcomes. We aim to describe the variation in care of Crohn disease as provided by a broad sample of pediatric gastroenterologists. METHODS: Two hundred forty-six Crohn disease patients of 93 pediatric gastroenterologists from 48 practice sites starting treatment with either thiopurine or infliximab were studied. We assessed variation in diagnostic testing that had been performed to establish the diagnosis of Crohn disease and to assess the phenotype, extent, and severity of disease. We also assessed variation in initial thiopurine and infliximab dosage and in nutritional therapy. RESULTS: Diagnostic studies in which care was uniform included complete blood count, performed in 100% of patients, erythrocyte sedimentation rate and colonoscopy in 96%, and upper endoscopy in 89%. However, imaging of the small bowel had not been performed in 19%, and a stool test for pathogens had not been performed in 29%. Thiopurine methyltransferase (TPMT) had been measured in 61% of patients before treatment with a thiopurine; in 85%, TPMT was normal. Nonetheless, even when TPMT was normal, 40% of patients received an initial dose of thiopurine that was lower than recommended. Testing for tuberculosis before initiating treatment with infliximab was not performed in 30%. In addition, 36% of severely underweight patients were not receiving a multivitamin supplement, supplemental formula, or tube feeding. CONCLUSIONS: There is variation in diagnostic and therapeutic interventions in the management of pediatric Crohn disease, and gaps exist between recommended and actual care.
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OBJECTIVES: Variation in medical care can be a barrier to improving clinical outcomes. We aim to describe the variation in care of Crohn disease as provided by a broad sample of pediatric gastroenterologists. METHODS: Two hundred ...
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OBJECTIVES: Variation in medical care can be a barrier to improving clinical outcomes. We aim to describe the variation in care of Crohn disease as provided by a broad sample of pediatric gastroenterologists. METHODS: Two hundred forty-six Crohn disease patients of 93 pediatric gastroenterologists from 48 practice sites starting treatment with either thiopurine or infliximab were studied. We assessed variation in diagnostic testing that had been performed to establish the diagnosis of Crohn disease and to assess the phenotype, extent, and severity of disease. We also assessed variation in initial thiopurine and infliximab dosage and in nutritional therapy. RESULTS: Diagnostic studies in which care was uniform included complete blood count, performed in 100% of patients, erythrocyte sedimentation rate and colonoscopy in 96%, and upper endoscopy in 89%. However, imaging of the small bowel had not been performed in 19%, and a stool test for pathogens had not been performed in 29%. Thiopurine methyltransferase (TPMT) had been measured in 61% of patients before treatment with a thiopurine; in 85%, TPMT was normal. Nonetheless, even when TPMT was normal, 40% of patients received an initial dose of thiopurine that was lower than recommended. Testing for tuberculosis before initiating treatment with infliximab was not performed in 30%. In addition, 36% of severely underweight patients were not receiving a multivitamin supplement, supplemental formula, or tube feeding. CONCLUSIONS: There is variation in diagnostic and therapeutic interventions in the management of pediatric Crohn disease, and gaps exist between recommended and actual care.
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OBJECTIVE: To describe the characteristics and systemic disease associations of episcleritis in childhood. DESIGN: Retrospective, observational case series. PARTICIPANTS: Twelve children diagnosed with episcleritis between July 19...
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OBJECTIVE: To describe the characteristics and systemic disease associations of episcleritis in childhood. DESIGN: Retrospective, observational case series. PARTICIPANTS: Twelve children diagnosed with episcleritis between July 1981 and June 1998. METHODS/TESTING: Complete eye and systemic evaluations. MAIN OUTCOME MEASURES: Characteristics of episcleritis and presence and nature of concurrent systemic disease. RESULTS: The 12 children (10 boys and 2 girls) ranged in age from 13 months to 16 years. Five children had bilateral simple episcleritis, one had bilateral nodular episcleritis, and six had unilateral simple episcleritis. The eye examination was otherwise normal and recovery was uneventful in all cases. Six of the nine children older than 5 years of age had one of the following rheumatologic diseases: systemic lupus erythematosus, juvenile rheumatoid arthritis, spondyloarthropathy, inflammatory bowel disease, rheumatic fever, or polyarteritis nodosa. All three children younger than 5 years of age had simple episcleritis, an antecedent viral illness, and presented within 2 months of each other. CONCLUSIONS: Episcleritis is a rare occurrence in childhood, especially in children younger than 5 years of age. In older children, it is frequently associated with rheumatologic disease.
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Introduction: The COX enzymes play a central role in the biosynthetic pathway of important biological mediators called prostanoids. Differences in regulation of gene expression, stability of transcripts and proteins determine the ...
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Introduction: The COX enzymes play a central role in the biosynthetic pathway of important biological mediators called prostanoids. Differences in regulation of gene expression, stability of transcripts and proteins determine the different biological functions of COX-1 and COX-2. While the COX-1 gene has been considered to be a housekeeping' gene expressed in many tissues and cells, COX-2 gene is upregulated during inflammation, hypoxia and in many cancers.Areas covered: The first part of this review provides a survey of the development of both modified traditional NSAIDs (tNSAIDs) and COX inhibitors (coxibs) with reduced side effects for the treatment of inflammation and cancer. The second part deals with patents reporting several dual inhibitors characterized by the conjugation of a COX-inhibitor scaffold to a molecule able to modulate a different target. Finally, two patents on novel COX inhibitor scaffolds are reported.Expert opinion: The most interesting branch of research concerns the conjugation of a COX-inhibitor scaffold to a molecule able to modulate a different target, in order to either enhance anti-inflammatory activity or to act as a dual inhibitor. Among the described compounds, selenium-containing coxibs inhibiting COX-2 and Akt, in addition to the multi-target biphenyl derivatives as dual inhibitors of COX and fatty acid amide hydrolase, are the most promising ones.
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Hygrophila schulli which is known as “Neermulli’’ in the vernacular is an herbaceous plant native to Sri Lanka. Ancient medicinal literature suggests the use of H. schulli whole plant or its parts for the treatment of different...
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Hygrophila schulli which is known as “Neermulli’’ in the vernacular is an herbaceous plant native to Sri Lanka. Ancient medicinal literature suggests the use of H. schulli whole plant or its parts for the treatment of different communicable and non-communicable diseases including diabetes mellitus and tuberculosis. Active constituents and secondary metabolites including alkaloids, tannins, steroids, proteins, flavonoids, and glycosides are identified to possess antimicrobial, antitumor, antioxidant, hepatoprotective, anthelmintic, nephroprotective, antidiabetic, anticataract, anti-inflammatory, anti-nociceptive, hematopoietic, diuretic, antiurolithiatic, antipyretic, neuroprotection, and anti-endotoxin activities. In this review, we reviewed clinical studies, patents, and analytical studies from the earliest found examples from 1886 to the end of 2021. We critically analyzed and attempt to summarize the information based on bioactivities and chemical composition of H. schulli plant extracts which will be of future use for researchers in this field.
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