Proinflammatory stimuli activates human-derived enteroglial cells and induces autocrine nitric oxide production.

BACKGROUND: Enteric glial cells (EGCs) have been recently indicated as key regulators of intestinal inflammation in animals. Whether or not this is true and how these cells participate to inflammatory responses in humans is unknown. METHODS: We isolated primary EGCs from human small bowel and then, we purified and characterized those using specific glial markers, such as S100B and glial fibrillary acidic protein (GFAP). To mimic an inflammatory scenario, we exposed EGCs to exogenous stimuli, such as lipopolysaccharide and interferon-gamma (LPS and IFN-γ), alone or in combination, to evaluate glial activation [measuring GFAP, S100B level together with c-fos, major histocompatibility complex (MHC) class II, inducible nitric oxide (iNOS) proteins expression and nitric oxide (NO) production] and proliferation, respectively. KEY RESULTS: We showed that, when challenged with a combination of LPS and IFN-γ, EGCs are significantly activated, as indicated by their positivity to c-fos and MHC class II. Similarly, pro-inflammatory stimuli significantly increase the cell proliferation rate, the expression of both S100B and GFAP, and the NO production consequent to the induction of EGCs-derived iNOS protein, with the last being dependent on S100B-RAGE (receptor for advanced glycation endproducts) interaction. CONCLUSIONS & INFERENCES: Our data provide the first evidence that human EGCs directly respond to pro-inflammatory stimuli by changing their expression profile and by proliferating. The finding that stimulated EGCs are able to produce NO points to a role of this cell population in the scenario of intestinal inflammation.

Efeito do envelhecimento sobre as propriedades resistivas e reativas do sistema respiratório / Effect of aging on the resistive and reactive properties of the respiratory system

Os sintomas respiratórios em idosos podem ser confundidos com modificações fisiológicas que introduz erros no processo de diagnóstico. Esta obra tem como objetivo investigar as modificações nas propriedades resistivas e reativas do sistema respiratório com o aumento da idade da técnica de oscilações forçadas...

Circannual rhythms of plasma growth hormone, thyrotropin and thyroid hormones in prepuberty.

To clarify the occurrence of circannual GH, TSH, T4 and T3 rhythms in prepuberty we have been studying, for a four year period, 150 healthy subjects, aged 6-10, by cross-sectional design. Plasma samples were taken at 0800 h and all hormones were measured by RIA. The occurrence of any circannual rhythm was statistically investigated by the cosinor method. A significant rhythm was validated (P = 0.02) only in TSH secretion, with annual crest time in December; GH, T4, T3 did not show a circannual rhythm. Our results seem to strengthen the hypothesis that the thyroid hormones, at least before puberty, do not play an important role in the regulation of circannual TSH periodicity.

Circannual rhythms of plasma luteinizing hormone, follicle-stimulating hormone, testosterone, prolactin and cortisol in prepuberty.

For a period of four years we have been studying 106 healthy males and 66 healthy females, aged 6-10, by cross-sectional design, to look for evidence of a circannual rhythm in LH, FSH, testosterone, PRL, and cortisol secretion. Plasma samples were taken at 0800 h and all hormones were measured by RIA. A cosine function was fitted to the single data to indicate any significant circannual (about 1 year) rhythm and to estimate its parameters: mesor, amplitude, and acrophase. Annual changes were validated in the secretion of: LH (annual crest time in January in both sexes), testosterone (studied only in males, annual crest time in July), and PRL (significant rhythm only in females with annual crest time in March). FSH and cortisol did not show an annual rhythm in both sexes. Our data suggest that sex influences the circannual hormonal rhythms from prepuberty onwards.

Change in circadian cortisol rhythmicity in patients with intracranial tumour.

To verify the influence of intracranial expanding processes on circadian cortisol rhythm, we studied its occurrence in 10 normal subjects, in 5 patients with extrasellar tumour, and in 3 patients with intracranial haematoma. All patients were tested every 4 h. Cortisol was measured by RIA. A cosine function was fitted to the data by mean cosinor method to evidence any rhythm and its parameters. A significant circadian rhythm was detected in the normal subjects with acrophase at 07.55 (07.15-08.25). The patients with extrasellar tumour and those with intracranial haematoma showed a lack of circadian rhythmicity due to a significant increase of cortisol levels at 20.00 and at 00.00, respectively. Our results suggest that study of the cortisol rhythm is useful, especially when an extrasellar tumour is suspected.

Temporal relationship between circannual levels of luteinizing hormone and testosterone in prepubertal boys with constitutional short stature.

In the present study we refer the results of our researches on LH and testosterone circannual variations in 72 prepubertal boys with constitutional short stature, aged 6 to 10 years. They observed the following life schedule: nocturnal rest from 2200 to 0600, meals at 0800, 1300, 1900. Plasma samples were taken at 0800 and LH and testosterone were measured by RIA. The single independent data were fitted a cosine function to evidence any rhythm and describe its parameters. A significant circannual rhythm in the LH (annual crest time in December) and testosterone (annual crest tine in July) levels was detected, with a phase difference between the two from about 160 degree to 180 degree, i.e. an antiphase. Our data suggest that a temporal relationship may occur between the circannual secretion of LH and testosterone in prepubertal boys.

Lack of nocturnal prolactin increase in patients with hypogonadotropic hypogonadism.

The circadian prolactin rhythm was studied in a group of 16 male adult volunteers: 10 healthy subjects and 6 patients affected by isolated hypogonadotropic hypogonadism (IHH). A significant nycto-hemeral prolactin rhythm (p = 0.0003, according to cosinor method) is detected in healthy subjects, but not in patients with IHH. In view of these results we may deem that the absence of nycto-hemeral variations of serum prolactin in subjects with IHH could be caused by failure of LH and FSH release.

[Effect of sex on annual variations in GH response to insulin hypoglycemia in prepuberal subjects of small stature]. / Influenza del sesso sulle variazioni circannuali della risposta del GH all'ipoglicemia insulinica in soggetti prepuberi con bassa statura.

86 males and 66 females, aged 6 to 10 years, affected by short stature (SDs -2 according to Tanner), were investigated from 1977 to 1979 in order to evidence any circannual rhythm in the GH response to insulin test. The patients were hospitalized one week before the study starting and they observed the following life schedule:nocturnal rest from 2200 to 0600, meals at 0800, 1300, 1800. The insulin test (0,1 UI/Kg body weight) were administered at 0800. Plasma samples were taken before and after 20, 40, 60, 90 minutes. The single basal data and the peak were fitted a cosine function by least square method in order to describe amy rhythm and to estimate its parameters:mesor, amplitude, acrophase. A significative circannual rhythm in the GH response to insulin is present in the female subjects, with acrophase in December (-354.85 degrees +/- 21.93). Our study suggest that the sex may influence the circannual response of GH to insulin stimulus from prepubertal age.

[Effect of sex on annual variations in plasma LH and FSH levels in prepubertal subjects]. / Influenza del sesso sulle variazioni circannuali dei livelli plasmatici di lh ed fsh in soggetti prepuberi.

We studied, from 1977 to 1979, 61 females and 72 males (aged 6 to 10 years) in order to demonstrate the occurrence of FSH and LH circannual variations. The data were fitted a cosine function by least square method in order to describe any rhythm and to estimate its parameters:mesor, amplitude, acrophase. Our data suggest that in prepubertal age the behaviour of FSH secretion is different in two sexes, but without circannual rhythm. LH instead shows a statistically significant circannual rhythm in both groups, without differences in mean levels between the two sexes.

[Annual variations in plasma testosterone levels in prepuberal subjects]. / Variazioni circannuali dei livelli di testosterone plasmatico in soggetti prepuberi.

40 prepubertal boys, aged 6 to 10 years, were studied from 1977 to 1979 in order to evidence any circannual rhythm in the testosterone plasmatic levels. The patients observed in the following life schedule: nocturnal rest from 2200 to 0600 circa, meals at 0800, 1300, 1900. Plasma samples were taken at 0800 and testosterone was assayed by RIA. Testosterone data were fitted a cosine function, by least square method in order to describe any rhythm and to estimate its parameters:mesor, amplitude, acrophase. A significative circannual rhythm in the testosterone levels is present (P= 0.008) with Acrophase in July (-198.38 degrees +/- 18.26 ES). Our study suggests that a significative testosterone rhythm, with circannual periodicity, is present also in prepubertal age.