Innate immune response mechanisms in non-insulin dependent diabetes mellitus patients assessed by flow cytoenzymology

Llórente, Luis; Fuente, Hortensia de la; Richaud‐Patin, Yvonne; Barrera, Claudia Alvarado-de la; Díaz-Borjón, Alejandro; López-Ponce, Alfredo; Lerman-Garber, Israel; Jakez‐Ocampo, Juan

doi:10.1016/s0165-2478(00)00255-8

Cited by 61 publications

(41 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This observation accords with earlier studies that mentioned a higher severity of infections in patients with diabetes (18). Specific factors like hyperglycemia-related impairment of the immune response, vascular insufficiency, sensory peripheral neuropathy, and autonomic neuropathy seem to be possible explanations for this increased severity of infections among diabetic patients (8,18,19). Another possible explanation for using more second-line antiinfectives is that children and adolescents with type 1 diabetes did not respond to the first-line anti-infectives that were initially prescribed and the physician was forced to prescribe a second-line anti-infective for them.…”

Section: Discussionsupporting

confidence: 94%

“…Children and adolescents with type 1 diabetes had prescriptions for more second-line anti-infectives compared with the reference cohort, including antibiotics which should be carefully prescribed in children and adolescents, such as quinolones (16,17). This observation accords with earlier studies that mentioned a higher severity of infections in patients with diabetes (18). Specific factors like hyperglycemia-related impairment of the immune response, vascular insufficiency, sensory peripheral neuropathy, and autonomic neuropathy seem to be possible explanations for this increased severity of infections among diabetic patients (8,18,19).…”

Section: Discussionsupporting

confidence: 82%

See 1 more Smart Citation

Population-Based Cohort Study of Anti-Infective Medication Use before and after the Onset of Type 1 Diabetes in Children and Adolescents

Farsani¹,

Souverein²,

Vorst³

et al. 2014

Antimicrob Agents Chemother

View full text Add to dashboard Cite

A population-based cohort study was conducted in the Dutch PHARMO database to investigate prevalence and patterns of antiinfective medication use in children and adolescents with type 1 diabetes (T1D) before and after the onset of this disease. All patients <19 years with at least 2 insulin prescriptions (1999 to 2009) were identified (T1D cohort) and compared with an age-and sex-matched (ratio: 1 up to 4) diabetes-free reference group. The prevalence and average number of anti-infective use was studied from (up to) 8 years before until a maximum of 4 years after the onset of T1D. A total of 925 patients with T1D and 3,591 children and adolescents in the reference cohort (51% boys, mean age of 10.1 [standard deviation, 4.5] years) were included. The overall prevalence of anti-infective use (62.6 compared to 52.6%, P < 0.001) and average number of prescriptions (2.71 compared to 1.42 per child, P < 0.001) in the T1D cohort were significantly higher than those in the reference cohort after the onset of diabetes. This pattern was consistent across sex and age categories and already observed in the year before the onset of type 1 diabetes. Patients in the T1D cohort received more antibacterials (49.8 compared to 40%, P < 0.001), antimycotics (4.0 compared to 1.3%, P < 0.001), antivirals (2.5 compared to 0.4%, P < 0.001), and second-line antibiotics, such as aminoglycosides, quinolones, and third-generation cephalosporins and carbapenems. Our findings that elevated anti-infective use in the T1D cohort exists in the period before the onset of type 1 diabetes and the consumption of more second-line anti-infective compounds in this time period warrant further research.

show abstract

Section: Discussionsupporting

confidence: 94%

Section: Discussionsupporting

confidence: 82%

Population-Based Cohort Study of Anti-Infective Medication Use before and after the Onset of Type 1 Diabetes in Children and Adolescents

Farsani¹,

Souverein²,

Vorst³

et al. 2014

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…Several groups have reported that patients with diabetes or hyperglycemia exhibit aberrant neutrophil responses (1,3,12,14,33,34). Other investigators, however, failed to detect a defect in neutrophil function (18,28). These discrepancies could be attributed to the metabolic status of the diabetic patients, differences in methodology, or underlying diseases or complications among the population groups.…”

Section: Discussionmentioning

confidence: 99%

Defects in Innate Immunity Predispose C57BL/6J-Lepr^db/Lepr^dbMice to Infection byStaphylococcus aureus

et al. 2009

View full text Add to dashboard Cite

Foot and ankle infections are the most common cause of hospitalization among diabetic patients, and Staphylococcus aureus is a major pathogen implicated in these infections. Patients with insulin-resistant (type 2) diabetes are more susceptible to bacterial infections than nondiabetic subjects, but the pathogenesis of these infections is poorly understood. C57BL/6J-Lepr db /Lepr db (hereafter, db/db) mice develop type 2 diabetes due to a recessive, autosomal mutation in the leptin receptor. We established a S. aureus hind paw infection in diabetic db/db and nondiabetic Lepr +/+ (+/+) mice to investigate host factors that predispose diabetic mice to infection. Nondiabetic +/+ mice resolved the S. aureus hind paw infection within 10 days, whereas db/db mice with persistent hyperglycemia developed a chronic infection associated with a high bacterial burden. Diabetic db/db mice showed a more robust neutrophil infiltration to the infection site and higher levels of chemokines in the infected tissue than +/+ mice. Blood from +/+ mice killed S. aureus in vitro, whereas db/db blood was defective in bacterial killing. Compared with peripheral blood neutrophils from +/+ mice, db/db neutrophils demonstrated a diminished respiratory burst when stimulated with S. aureus. However, bone marrow-derived neutrophils from +/+ and db/db mice showed comparable phagocytosis and bactericidal activity. Our results indicate that diabetic db/db mice are more susceptible to staphylococcal infection than their nondiabetic littermates and that persistent hyperglycemia modulates innate immunity in the diabetic host.

show abstract

“…Development of analytical methods involves a search for specific and sensitive substrates (beta-endorphin, synthetic fluorogenic peptides) and new analytical techniques: HPLC [145,220], capillary electrophoresis [221][222][223], fluorimetry in the near infrared region [224], flow cytofluorimetry [225][226][227][228][229], western blot [230][231][232], immunohistochemical techniques [168,169], fluorescence microscopy [233,234] and electron microscopy [235,236].…”

Section: Resultsmentioning

confidence: 99%

Quantitative determination and localization of cathepsin D and its inhibitors.

Minarowska

Karwowska²,

Gacko³

2009

Folia Histochem Cytobiol.

View full text Add to dashboard Cite

Cathepsin D (EC 3.4.23.5) is a lysosomal aspartyl endopeptidase, localized in all cells and tissues, except for mature erythrocytes [1][2][3]. Methods used to determine the activity, concentration and cellular distribution of cathepsin D, but not its inhibitors, have previously been the subject of literature reports [4][5][6][7][8][9][10][11][12]. However, since the time of their publication a number of new substrates and analytical techniques have been implemented. Structure, specificity, mechanism of actionCathepsin D is synthesized in the rough endoplasmic reticulum as preprocathepsin D, built up of 412 amino acid residues [13][14][15]. As a result of cleavage of the 20-amino acid signal prepeptide, it is converted into procathepsin D which undergoes glycosylation and disulphide bridges are formed in its molecule. Procathepsin D is transported from cisterns of the rough endoplasmic reticulum to the Golgi apparatus, from which, with the involvement of mannoso-6-phosphate (M-P-6) receptors, it is transferred to primary lysosomes [16,17]. As the M-6-P receptors are known to occur in the primary lysosomes but not in the mature ones, they can be used to distinguish between these two types of lysosomes [18]. In the acidic environment of the lysosomes (pH 4.5-5.5), due to autocatalytic cleavage of the 44-amino acid propeptide from the N-terminal molecule, procathepsin D is converted into the active one-chain form. The actions of cysteine proteinase, aminopeptidases and carboxypeptidases lead to the formation of an active two-chain form of cathepsin D (Fig. 1). These chains are bound by hydrophobic bonds. The molecular weight of the ultimate mature form of cathepsin D is 48 (14+34) kDa. The proteolytic activities of the one-chain and two-chain forms are very similar [19,20]. Modification of the polypeptide chain, different oligosaccharide composition types and phosphorylation/dephosphorylation in the amino saccharide residues contribute to marked molecular heterogenicity of cathepsin D and cause differences in isoelectric points of the respective isoenzymes between pH 4.5 -6.5 [21,22].The use of peptides with the known primary structure allows identification of amino acid residues that form peptide bonds cleaved by cathepsin D. For this purpose, synthetic peptides [23] and chains A and B of bovine insulin can be used (Fig. 2). Cathepsin D cleaves the peptide bonds found within the polypeptide chain, formed by carboxyl groups of the hydrophobic amino acid residues: aromatic -trypto-

show abstract

Innate immune response mechanisms in non-insulin dependent diabetes mellitus patients assessed by flow cytoenzymology

Cited by 61 publications

References 22 publications

Population-Based Cohort Study of Anti-Infective Medication Use before and after the Onset of Type 1 Diabetes in Children and Adolescents

Population-Based Cohort Study of Anti-Infective Medication Use before and after the Onset of Type 1 Diabetes in Children and Adolescents

Defects in Innate Immunity Predispose C57BL/6J-Lepr^db/Lepr^dbMice to Infection byStaphylococcus aureus

Quantitative determination and localization of cathepsin D and its inhibitors.

Contact Info

Product

Resources

About

Innate immune response mechanisms in non-insulin dependent diabetes mellitus patients assessed by flow cytoenzymology

Cited by 61 publications

References 22 publications

Population-Based Cohort Study of Anti-Infective Medication Use before and after the Onset of Type 1 Diabetes in Children and Adolescents

Population-Based Cohort Study of Anti-Infective Medication Use before and after the Onset of Type 1 Diabetes in Children and Adolescents

Defects in Innate Immunity Predispose C57BL/6J-Leprdb/LeprdbMice to Infection byStaphylococcus aureus

Quantitative determination and localization of cathepsin D and its inhibitors.

Contact Info

Product

Resources

About

Defects in Innate Immunity Predispose C57BL/6J-Lepr^db/Lepr^dbMice to Infection byStaphylococcus aureus