c-peptide and Pneumonia

C-peptide is a 31-amino acid peptide cleaved from proinsulin during insulin synthesis. Initially thought to be inert, C-peptide may modulate the inflammatory response in the setting of endotoxemia and ischemia reperfusion. However, the spectrum of its biological effects is unclear. We hypothesized that exogenous administration of C-peptide would modulate pro- and anti-inflammatory signaling pathways and thereby attenuate lung inflammation in an in vivo model of hemorrhagic shock. Hemorrhagic shock was induced in male Wistar rats (aged 3-4 mo) by withdrawing blood to a mean arterial pressure of 50 mmHg. At 3 h after hemorrhage, rats were rapidly resuscitated by returning their shed blood. At the time of resuscitation and every hour thereafter, animals received C-peptide (280 nmol/kg) or vehicle parenterally. Animals were euthanized at 1 and 3 h after resuscitation. C-peptide administration at resuscitation following hemorrhagic shock ameliorated hypotension and blunted the systemic inflammatory response by reducing plasma levels of IL-1, IL-6, macrophage inflammatory protein-1α, and cytokine-induced neutrophil chemoattractant-1. This was associated with a reduction in lung neutrophil infiltration and plasma levels of receptor for advanced glycation end products. Mechanistically, C-peptide treatment was associated with reduced expression of proinflammatory transcription factors activator protein-1 and NF-κB and activation of the anti-inflammatory transcription factor peroxisome proliferator-activated receptor-γ. Our data suggest that C-peptide ameliorates the inflammatory response and lung inflammation following hemorrhagic shock. These effects may be modulated by altering the balance between pro- and anti-inflammatory signaling in the lung.

Topics: Animals; C-Peptide; Cytokines; Male; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Neutrophil Infiltration; NF-kappa B; Pneumonia; PPAR gamma; Rats; Rats, Wistar; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Resuscitation; Shock, Hemorrhagic; Transcription Factor AP-1; Tumor Necrosis Factor-alpha

Hyperinsulinemic hypoglycemia associated with trimethoprim-sulfamethoxazole (TMP-SMX) has generally been reported in adults who had renal impairment or in patients with AIDS using high dose TMP-SMX. We present a 5 month-old infant with immunodeficiency due to major histocompatibility complex class II expression defect, developing hypoglycemic convulsion on the third day of high dose TMP-SMX administration. High insulin and C-peptide levels were documented at the time of hypoglycemia. To overcome hypoglycemia while TMP-SMX tapered off, diazoxide was administered which resolved hypoglycemia in 2 months.

Topics: Blood Glucose; C-Peptide; Diazoxide; Drug Administration Schedule; Female; Gene Expression; Genes, MHC Class II; Glucose; Histocompatibility Antigens Class II; Hospitalization; Humans; Hyperinsulinism; Hypoglycemia; Immunologic Deficiency Syndromes; Infant; Infusions, Intravenous; Pneumonia; Seizures; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To clarify which endocrine modifications can be observed in acute hypoxaemic respiratory failure, 15 severely ill male patients [PAT; median age: 61 (range: 48 years); median height: 173 (range: 12) cm; median mass: 73 (range 31) kg] were investigated immediately upon admission to an intensive care unit (ICU) for this clinical disorder. Before starting treatment, the blood gases were measured and a number of selected hormones with special relevance for an ICU setting were determined. These are known to be modified by acute hypoxaemia in healthy subjects and to possess glucoregulatory properties, or an influence upon cardiocirculation or the vascular volume regulation: insulin, cortisol, adrenaline, noradrenaline, atrial natriuretic peptide, renin, aldosterone, angiotensin converting enzyme, and endothelin-I (ET). To elucidate whether potential endocrine changes resulted from acute hypoxaemia alone, the underlying disease, or unspecific influences connected with the ICU setting, all measurements were compared to those of a completely healthy reference group (REF) with comparable acute experimental hypoxaemia. The latter state was achieved by having the REF breathe a gas mixture with the oxygen content reduced to 14% (H). In the REF, neither the medians nor the distribution of endocrinologic measurements were modified significantly by acute hypoxaemia. In the PAT, the medians were increased considerably, yet with a slight diminution of ET. The distribution of individual values was considerably broader than in the REF with H. In conclusion, considerable increases in the means of the above hormones, with the exception of ET, can be registered in severely ill patients admitted to ICUs with acute hypoxaemic failure. However, such modifications cannot be considered attributable exclusively to acute arterial hypoxaemia. The underlying clinical disorders, such as septicaemia or an unspecific endocrine epiphenomenon, including severe and not only hypoxaemic stress, seem to be predominant.

Topics: Acute Disease; Adult; Aged; Aldosterone; Atrial Natriuretic Factor; C-Peptide; Critical Care; Endocrine Glands; Endothelins; Epinephrine; Humans; Hydrocortisone; Hypoxia; Insulin; Male; Middle Aged; Norepinephrine; Peptidyl-Dipeptidase A; Pneumonia; Renin; Respiratory Insufficiency