Insulin treatment enhances expression of IGF-I in sural nerves of diabetic patients.

We studied the expression of insulin-like growth factor I (IGF-I) and its receptor in sural nerves from 8 diabetic patients divided into insulin-treated (IT) and non-insulin-treated (NIT) groups, compared with 5 patients with axonal neuropathies and 4 control patients (undergoing biopsies for diagnostic purposes). Insulin-like growth factor I mRNA levels did not differ in diabetic cases compared with control subjects. In sural nerves from IT patients and axonal neuropathies, IGF-I expression was higher than in NIT subjects and diagnostic controls. Changes in IGF-I receptor mRNA levels paralleled those of the ligand. Insulin-like growth factor I immunoreactivity was higher in nerves undergoing axonal degeneration and higher in IT than NIT diabetic patients and diagnostic controls. These findings suggest that insulin treatment increases IGF-I expression in diabetic nerves. Our data do not support the hypothesis of an absolute IGF-I deficiency in human diabetic neuropathy. A Schwann cell's incapacity to increase IGF-I expression after severe nerve damage, as happens in axonal neuropathies, may be a cofactor in the pathogenesis of diabetic neuropathy.

Vasculitic neuropathy associated with beta-haemolytic streptococcal infection: a case report.

Vasculitic neuropathy is rarely associated with a definable collagen vascular disease. Peripheral neuropathy may be the sole manifestation of vasculitis, and the aetiology is frequently unknown. We here report the case of a woman presenting mononeuritis multiplex, whose sural nerve biopsy was diagnostic of necrotizing vasculitis. There was serological evidence of preceding beta-haemolytic streptococcal infection. We assume that vasculitic neuropathy can be included among the possible sequelae of streptococcal infections.

Cellular cytotoxicity mediated by granule-depleted neutrophil cytoplasts.

Neutrophil-derived nucleus-and granule-free cytoplasts, consisting of cytosol enclosed by an intact plasma membrane, were able to destroy 51Cr-labelled ox red blood cells (ORBC) in the presence of phorbol myristate acetate (PMA). The slope of the target cell lysis vs the log of the cytoplast number was similar to that observed with neutrophils as effector cells. Nevertheless, a number of cytoplasts 60-80 times higher than that of neutrophils was required to obtain a common level of cytotoxicity. The ability of cytoplasts and neutrophils to lyse ORBC was completely abolished by catalase and unaffected by superoxide dismutase and mannitol, suggesting the involvement of hydrogen peroxide in the target cell damage. Addition of myeloperoxidase (MPO) to cytoplasts increased lysis. The MPO lysis by cytoplasts, except when experiments were carried out in the presence of MPO. The results indicate that neutrophil cytosol and plasma membrane represent the basic requirement for the PMA-dependent cytolytic process, whereas MPO behaves as a device to amplify lysis.

Phagocytosis-dependent neutrophil-mediated extracellular cytotoxicity against different target cells.

Normal human neutrophils, incubated with 0.2 mg/ml opsonized zymosan particles, were found to lyse human (H), ox (O) and chicken (C) red blood cell (RBC) targets as determined by the 51Cr release assay. The susceptibility to the lysis of the different target cells was HRBC less than ORBC less than CRBC. An intact neutrophil metabolic burst was essential for the cytotoxic event, since neutrophils from a patient with chronic granulomatous disease failed to kill all three target cells. HRBC and ORBC destruction was prevented by catalase and unaffected by azide, suggesting the requirement of hydrogen peroxide alone in the lethal hit. CRBC destruction was abolished by catalase and azide, suggesting the involvement of the myeloperoxidase-hydrogen peroxide system. Thus, different neutrophil cytolytic systems may become operative and may vary in their efficiency depending on the type of target cells.