ER-phagy drives age-onset remodeling of endoplasmic reticulum structure-function and lifespan.

The endoplasmic reticulum (ER) comprises an array of structurally distinct subdomains, each with characteristic functions. While altered ER-associated processes are linked to age-onset pathogenesis, whether shifts in ER morphology underlie these functional changes is unclear. We report that ER remodeling is a conserved feature of the aging process in models ranging from yeast to C. elegans and mammals. Focusing on C. elegans as an exemplar of metazoan aging, we find that as animals age, ER mass declines in virtually all tissues and ER morphology shifts from rough sheets to tubular ER. The accompanying large-scale shifts in proteomic composition correspond to the ER turning from protein synthesis to lipid metabolism. To drive this substantial remodeling, ER-phagy is activated early in adulthood, promoting turnover of rough ER in response to rises in luminal protein-folding burden and reduced global protein synthesis. Surprisingly, ER remodeling is a pro-active and protective response during aging, as ER-phagy impairment limits lifespan in yeast and diverse lifespan-extending paradigms promote profound remodeling of ER morphology even in young animals. Altogether our results reveal ER-phagy and ER morphological dynamics as pronounced, underappreciated mechanisms of both normal aging and enhanced longevity.

Assessment of the awareness and management of sleep apnea syndrome in acromegaly. The COM.E.TA (Comorbidities Evaluation and Treatment in Acromegaly) Italian Study Group.

In 2007 the Italian COM.E.T.A. (COMorbidities Evaluation and Treatment in Acromegaly) study group started to assess the application in a clinical setting of the Versailles criteria for management of acromegaly complications by a first questionnaire focusing on cardiovascular co-morbidities. A further questionnaire on sleep apnea syndrome (SAS) was delivered by the COM.E.T.A. study group to 107 endocrine centers in Italy. The results of our survey suggest that SAS is a well-known comorbidity even if its estimated prevalence is lower than in the literature. Polysomnography is the preferred tool for diagnosis. Control of SAS is considered relevant both for quality of life and co-morbidities. Continuous positive airway pressure is the cornerstone of therapy, but patients' acceptance may be critical. Control of GH/IGF-I secretion is important to improve SAS. Management of SAS requires cooperation between specialists.

APAP titration in patients with mild to moderate OSAS and periodic limb movement syndrome.

AIMS: 1) to evaluate automatic positive airway pressure (APAP) titration in a partially attended setting; 2) to verify whether APAP performance depends on the apnea-hypopnea and periodic limb movement indexes (PLMI). METHODS: 65 CPAP naïve subjects with a sleep disorder of breathing and daytime sleepiness underwent a standard polysomnography (first night), APAP titration (second night, partially attended), and a standard polysomnography using continuous positive airway pressure (CPAP) at the effective pressure (Peff) established from the APAP titration (third night) in a sleep disorder laboratory in a 400-bed community hospital. We examined the apnea-hypopnea index (AHI), sleep stages, arousals induced by respiratory events (RESPa) and PLM (PLMa), and oxygen saturation during the first and third nights on CPAP at the Peff. Patients were divided into three groups according to their AHI and PLMI. RESULTS: At the Peff defined using APAP on the third night, the mean AHI dropped from 29.6 +/- 21.8 to 3.1 +/- 3.4, and the RESPa index from 16.5 +/- 16.2 to 1.7 +/- 2.6. No differences emerged in sleep stages or spontaneous arousals (first vs third night). Overall, 92% of the patients met the standard for an acceptable outcome of positive pressure titration. Baseline AHI and PLMI did not affect the outcome of titration. CONCLUSIONS: In patients with mild to moderate OSAS and PLMS, APAP titration enables the optimal fixed pressure for CPAP home therapy to be determined in at least 90% of patients.

Ante mortem diagnosis of primary leiomyosarcoma of the pulmonary artery.

Primary leiomyosarcoma of the pulmonary artery is an extremely rare tumor. A definite diagnosis has always been made at autopsy. We describe a primary leiomyosarcoma with atypical features. The tumor arose from the right pulmonary artery and was diagnosed by bronchoscopic biopsy.

A vagabond pleural pebble.

This article concerns a case of an extremely mobile pulmonary opacity. This opacity was attributed to a free calcified mass in the pleural space. It is probably a small benign neoplasm whose peduncle underwent necrosis.

Determination of antibodies to Borrelia burgdorferi in sarcoidosis.

Borrelia burgdorferi, i.e. the etiologic agent of Lyme disease, has been causatively linked to sarcoidosis. To evaluate the possible role of this spirochete in the pathogenesis of sarcoidosis we tested for the presence of antibodies to B. burgdorferi on serum samples obtained from 21 sarcoid patients living in an Italian mountain area where Lyme borreliosis is endemic. No patient showed antibodies to B. burgdorferi. Our data does not substantiate the hypothesis that sarcoidosis may be a borreliosis.

Activated T-lymphocytes and macrophages in bronchial mucosa of subjects with chronic bronchitis.

To examine the nature and the degree of leukocyte infiltration and to determine the state of activation of cells in bronchial mucosa of subjects with chronic bronchitis, bronchoscopy was performed in 10 subjects with a history of cigarette smoking and chronic sputum production and in six normal nonsmoking control subjects. Lobar bronchial biopsies were examined using histochemical and immunohistochemical techniques. Subjects with chronic bronchitis had an increased number of total leukocytes (CD45 positive cells), both in the epithelium and in the lamina propria, than did the control subjects (p < 0.05), whereas the numbers of neutrophils, eosinophils, and mast cells were similar in the two groups. There was a significant increase in the numbers of macrophages (p < 0.01) and of T-lymphocytes (CD3 positive cells) (p < 0.05) in the lamina propria of chronic bronchitics, whereas the relative proportions of CD4 and CD8 positive cells were similar in the bronchitics and the control subjects. Subjects with chronic bronchitis also had an increased expression of markers of lymphocyte activation, i.e., an increased number of interleukin-2 receptor positive cells (CD25 positive cells) (p < 0.05) and an increased number of very late activation antigen (VLA-1) positive cells (p < 0.05). In conclusion, the present study provides evidence for mononuclear cell infiltration and for T-cell activation in bronchial mucosa of subjects with chronic bronchitis, supporting the involvement of these cells in the pathogenesis of the disease.