Leptin is an adipokine with roles in food intake and energy metabolism through its actions on neurons in the hypothalamus. The role of leptin in obesity and cardiovascular disorders is well ...documented. However, its influence on liver conditions such as cholestasis is poorly understood. The effects of exogenous leptin and leptin-neutralizing antibody on biliary hyperplasia, hepatic fibrosis, and inflammation in the multidrug resistance protein 2 knockout (Mdr2KO) mouse model of cholestasis were assessed by quantifying markers specific for cholangiocytes, activated hepatic stellate cells (HSCs), and cytokines. Serum and hepatic leptin were increased in Mdr2KO mice compared with FVB/NJ (FVBN) controls, and exogenous leptin enhanced biliary hyperplasia and liver fibrosis in Mdr2KO and FVBN mice. Leptin administration increased hepatic expression of C-C motif chemokine ligand 2 and IL-6 in Mdr2KO mice. In contrast, leptin-neutralizing antibody reduced intrahepatic bile duct mass and decreased HSC activation in Mdr2KO mice compared with FVBN controls. Sex-related differences were noted, with female Mdr2KO mice having more leptin than males. In cholangiocytes and LX2 cells in vitro, leptin increased phosphorylated Akt and stimulated cell proliferation. Leptin receptor siRNA and inhibitors of Akt phosphorylation impaired leptin-induced cell proliferation and proinflammatory cytokines. The current data suggest that leptin is abnormally increased in cholestatic mice, and excess leptin increases ductular reaction, hepatic fibrosis, and inflammation via leptin receptor–mediated phosphorylation of Akt in cholangiocytes and HSCs.
Background Imported fire ants (IFAs) are endemic in the southeastern United States, including Texas; can sting multiple times; and are a well-known cause of anaphylaxis. There are few data available ...on how many stings typically lead to systemic reactions (SRs). Likewise, there are no reports currently in the literature that characterize the safety of IFA subcutaneous immunotherapy (SCIT). Objective We sought to analyze a case-cohort sample of patients for IFA SCIT risk factors and to characterize the index field reactions of these patients. Methods A case-cohort study based on a 3-year retrospective chart review (2005-2008) at a single institution was performed for patients receiving IFA SCIT. Field reactions leading to initiation of IFA SCIT were also reviewed. Results Seventy-seven patients (40 female patients; mean age, 34 years) received 1,887 injections, and 7 patients experienced 8 SRs, for a rate of 0.4% per injection and 9.1% per patient. SRs were mild. Having an SR to skin testing was associated with increased odds of having an SR to IFA SCIT (odds ratio, 4.75; 95% CI, 1.13-20.0), as were large local reactions (odds ratio, 34.5; 95% CI, 6.52-182). No other risk factors were identified. Of the index field reactions leading to IFA SCIT, 59% were the result of 1 sting, and 87% of subjects experienced only 1 SR before initiation of IFA SCIT. Two of 4 patients who experienced loss of consciousness during the index field reaction required an increased maintenance dose for optimal response. Conclusions IFA SCIT is safe; however, having an SR to skin testing or the presence of large local reactions increases the odds of having an SR to IFA SCIT. The majority of SRs to IFA field stings resulted from 1 sting.
S2422 Metastatic Melanoma With GI Involvement Jones, Mauricio; Shell, Mark; Erikson, Richard
The American journal of gastroenterology,
10/2023, Letnik:
118, Številka:
10S
Journal Article
Dexamethasone for Bronchiolitis La Shell, Mark S; Calabria, Christopher W
The New England journal of medicine,
10/2007, Letnik:
357, Številka:
16
Journal Article
Recenzirano
To the Editor:
The prospective trial of dexamethasone for bronchiolitis in infants, conducted by the Bronchiolitis Study Group of the Pediatric Emergency Care Applied Research Network (PECARN) and ...reported by Corneli et al. (July 26 issue),
1
appears to demonstrate a lack of efficacy of oral dexamethasone in infants with a first episode of wheezing diagnosed as bronchiolitis. Although the authors aptly conclude that dexamethasone did not provide a benefit in the first 7 days after treatment, they fail to address the fact that treatment with oral steroids may prevent recurrent wheezing in the months after infection, particularly in first-time wheezing . . .
Antibiotics for the allergist: part 2 La Shell, Mark S; Tankersley, Michael S
Annals of allergy, asthma, & immunology
102, Številka:
1
Journal Article
Recenzirano
To review antibiotic use and selection for disorders commonly seen in allergy practice.
MEDLINE searches were performed cross-referencing antibiotic, antimicrobial, management, and treatment with ...multiple disorders commonly seen in allergy practice. References of the chosen articles were also examined.
Articles were selected based on their relevance to the subject matter.
A large body of research is available relevant to both conventional and novel uses of antibiotics. The use of antibiotics is in question for some disorders, whereas novel approaches to therapy with macrolide antibiotics are areas of active investigation. Meanwhile, patterns of microbial resistance continue to evolve.
For decades, antibiotics have been traditional first-line treatment for many disorders. Currently, this paradigm appears to be shifting as periods of observation come into favor and nonbacterial causes of inflammation are under greater scrutiny. Nonetheless, appropriate antibiotic selection often remains a key element in the treatment of these disorders. Knowledge of the relevant microbiology is an inherent requirement in selecting antibiotic therapies and necessitates awareness of current trends in bacterial resistance.
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