Increased activity of plasma and tissue kallikreins, plasma kininase II and salivary kallikrein in pemphigus foliaceus (fogo selvagem).

BACKGROUND: Pemphigus foliaceus (PF) is an autoimmune blistering disease of unknown aetiology, which is endemic in Brazil. Although the pathogenesis of PF is still unknown, proteins of the contact system have been implicated. OBJECTIVES: As the components of the kinin system may interact with those of the contact system, in this study we evaluated the plasma levels of high-molecular-weight kininogen (HK) and low-molecular-weight kininogen (LK), and the activity of plasma kallikrein, tissue kallikrein and kininase II in plasma of patients with PF presenting with Nikolsky's sign. As kidneys and salivary glands are relevant sources of tissue kallikrein for plasma, we also evaluated urinary/salivary kallikrein and urinary kininase II activities. METHODS: Fifteen patients and 15 age- and sex-matched controls were studied. Kininogen levels were determined by enzyme-linked immunosorbent assay, and the activities of kallikreins and kininase II were determined using selective chromogenic substrates. RESULTS: Compared with controls, plasma HK levels were decreased (P = 0.031), whereas the activities of plasma kallikrein, tissue kallikrein and kininase II in plasma, and the activity of salivary kallikrein, were increased in patients (P < 0.001 for each comparison). Plasma levels of LK and the activities of urinary kallikrein and urinary kininase II were not significantly different from controls. CONCLUSIONS: Diminished levels of HK associated with increased activities of plasma kallikrein and kininase II indicate that the kinin system is activated at the systemic level in PF. As active plasma kallikreins may act on some proteins of the contact system, it is possible that the enzyme may contribute to blister formation. The further observation of an increased tissue kallikrein activity at the systemic and saliva levels may be interpreted as a systemic reflex of skin inflammation. Whether the activation of the kinin system is a cause or a consequence of blister formation needs further clarification.

[Noonan's syndrome associated with cerebral hemorrhage. Report of a case]. / Sindrome di Noonan associata ad emorragia cerebrale. Descrizione di un caso.

The prevalence of Noonan syndrome has been estimated at between 1 out of 1000 and 1 out of 2500 live births; it is often confused with Turner syndrome because the two conditions display a common phenotype. Even if Noonan syndrome is typically associated with congenital heart diseases, prognosis is generally good. We describe the case of a female patient, deaf from infancy, in whom the presence of obstructive cardiomyopathy had been previously demonstrated angiographically at 29 years of age. A diagnosis of Turner syndrome had been made on the basis of her physical features. One year later she began to complain of accessional headache with nausea; seizures occurred at 48 years of age. The patient suddenly died during a hospital stay for investigation of these symptoms. Autopsy evidenced multiple cerebral hemorrhages due to vascular anomalies. She had normal female genitalia. This case demonstrates that Noonan syndrome is still misdiagnosed, and that it may have various clinical symptoms. In particular, it underscores the opportunity of carrying out systematic research on cerebrovascular abnormalities in these patients because they are potentially fatal.

[In vitro effects of IL-2 on human hypophyseal adenoma]. / Effetti in vitro della IL-2 su adenomi ipofisari umani.

The effects of two different concentrations of IL-2 on human pituitary adenomas (one secreting ACTH and one secreting GH) were evaluated in vitro. A specimen of the tumor was dissagregated and the cells were incubated for three days with RPMI 1640 medium. The medium was then decanted and the cells were incubated with 1 mlo of fresh medium for three hours and then with new fresh medium containing two different concentrations of IL-2, 100U/ml, for three hours too. The pituitary hormones, ACTH and GH, released into the medium were assayed by RIA. Dose of 100 U IL-2 induced a profound increase of ACTH release. The other dose decreased ACTH release. The release of GH was suppressed by IL-2 at the two concentrations tested. IL-2 may be an immunologic messenger exerting direct action at pituitary level. It appears probable that IL-2 plays an important role in determining the response of the pituitary to stress and infections.