Ergosterol reduction impairs mitochondrial DNA maintenance in S. cerevisiae

Sterols are essential lipids, involved in many biological processes. In Saccharomyces cerevisiae, the enzymes of the ergosterol biosynthetic pathway (Erg proteins) are localized in different cellular compartments. With the aim of studying organelle interactions, we discovered that Erg27p resides mainly in Lipid Droplets (LDs) in respiratory competent cells, while in absence of respiration, is found mostly in the ER. The results presented in this paper demonstrate an interplay between the mitochondrial respiration and ergosterol production: on the one hand, rho° cells show lower ergosterol content when compared with wild type respiratory competent cells, on the other hand, the ergosterol biosynthetic pathway influences the mitochondrial status, since treatment with ketoconazole, which blocks the ergosterol pathway, or the absence of the ERG27 gene, induced rho° production in S. cerevisiae. The loss of mitochondrial DNA in the ∆erg27 strain is fully suppressed by exogenous addition of ergosterol. These data suggest the notion that ergosterol is essential for maintaining the mitochondrial DNA attached to the inner mitochondrial membrane

Long-term survival of atypical bronchial carcinoids with liver metastases, treated with octreotide

OBJECTIVE: To demonstrate that liver metastases by radically resected atypical carcinoids of the lung can be effectively treated by new somatostatin analogs. METHODS: Between January 1977 and December 1999, 126 patients affected by bronchial carcinoids were submitted to a radical resection of the lung. Seven of them (5.5%) presented liver metastases 27, 22, 14, 18, 16, 12 and 9 months after surgery: carcinoid syndrome (CS) was ever present. 111In-DTPA-pentetreotide scintigraphy (Octreoscan) and ultrasound guided biopsy were performed in all cases, and the presence of somatostatin receptors sst2 was demonstrated by polymerase chain reaction (PCR) method. RESULTS: Five patients refused the proposed chemotherapy, and liver alcoholization was not feasible. Octreotide was administered at the dose of 1500 microg/daily subcutaneously. CS was controlled and also high urinary 5-hydroxyindoleacetic acid values returned to normal after a median of 7 days (range 4-10 days) of medical treatment. No important side effects were registered, and a good quality of life was observed. The patients are alive and well at 51, 36, 24, 24, 23, 19, and 16 months after the diagnosis of the metastases, respectively. In two cases ultrasounds revealed the reduction and in one case the complete resolution of the liver lesion. CONCLUSIONS: Octreotide is effective in controlling symptoms of CS of patients with liver metastases of resected atypical bronchial carcinoid. The efficacy of the drug is due to the presence of sst2 somatostatin receptors in the pathologic tissue, as demonstrated by PCR method. The positivity to Octreoscan depends on the presence of the same receptors. Octreoscan may be used in the follow-up of these neuroendocrine neoplasms of the lung. A positivity to Octreoscan is predictive for an effective therapy with octreotide

When size matters: changing opinion in the management of pleural space-the rise of small-bore pleural catheters

Tube thoracostomy is usually the first step to treat several thoracic/pleural conditions such as pneumothorax, pleural effusions, haemothorax, haemo-pneumothorax and empyema. Today, a wide range of drains is available, ranging from small to large bore ones. Indications for an appropriate selection remains yet matter of debate, especially regarding the use of small bore catheters. Through this paper, we aimed to retrace the improvements of drains through the years and to review the current clinical indications for chest drain placement in pleural/thoracic diseases, comparing the effectiveness of small-bore drains vs. large-bore ones

Solitary fibrous tumour of the pleura: surgical treatment

OBJECTIVE: Solitary fibrous tumours (SFT) of the pleura are rare tumours originated from the mesenchimal tissue underlying the mesothelial layer of the pleura. This tumours present unpredictable clinical course probably related to their histological and morphological characteristics. METHODS: Twenty-one patients affected by SFT of the pleura were referred to us for surgical resection from September 1984 to April 2000. They were 15 males and six females with median age of 51 (range 15--73) years. Nine patients (43%) were symptomatic and predominant clinical symptoms or signs were dyspnoea (19%), coughing (14.3%), chest pain (28.5%), finger clubbing (14.3%) and hypoglycaemia (14.3%). Hypoglycaemia was related to a pathological incretion of insulin-like growth factor 2 by the tumour. Chest radiograph and computed tomography of the chest revealed intra-thoracic homogeneous sharply delineated round or lobulated mass sometimes associated with ipsilateral pleural effusion (19%) or causing pulmonary atelectasis with opacification of the complete hemithorax (19%). Surgical excision required 14 posterolateral thoracotomies, six anterior thoracotomies and one video-assisted thoracoscopy. Thirteen tumours arose from visceral pleura and wedge resection was performed, seven tumours arose from parietal pleura and extrapleural resection was carried out without any chest-wall resection, one tumour growth within the upper left lobe and required lobectomy. Tumours weighted from 22 to 1942 g and measured from 22x12x8 to 330x280x190 mm. At cut section seven cases (34%) revealed focal necrosis and hemorrhagic zones and on light microscopy six cases (28.5%) were characterized by high mitotic count: characteristics related with uncertain clinical behaviour. Immuno-histochemical reactions were in all cases positive for CD34. RESULTS: In all our patients resections were complete. Paraneoplastic syndromes like hypoglycaemia and clubbing receded after surgery. No intraoperative or perioperative medical or surgical complications occurred. Median chest-drain duration timed 3 (range 2--5) days and median hospital stay was 5 (range 4--7) days. Perioperative mortality rate was 0%. Median follow-up was 68 (range 2--189) months: during this period patients were submitted to chest X-ray with 6-months interval to evaluate possible local recurrence. Only one patient experienced tumour recurrence after 124 months follow-up: the tumour was suspected after observation of finger clubbing. The tumour was detected and excised by redo-thoracotomy. CONCLUSIONS: Surgical resection of benign solitary fibrous tumours is usually curative, but local recurrences can occur years after seemingly adequate surgical treatment. Malignant solitary fibrous tumours generally have a poor prognosis. Clinical follow-up and radiological follow-up are indicated for both benign and malignant solitary fibrous tumours

Bronchial carcinoid tumors: surgical management and long-term outcome

OBJECTIVE: We sought to determine the variables influencing long-term survival of patients treated for bronchial carcinoid tumors. METHODS: A retrospective, mono-institutional review of patients subjected to surgical treatment since 1977 was conducted. RESULTS: Over 22 years, 126 patients with a final histologic diagnosis of bronchial carcinoid tumors were assessed for surgery. The group comprised 72 men (57%) and 54 women (43%) with a mean age at presentation of 47 +/- 16 years (range 11-77 years). Symptoms were present in 65 (53%) patients. Operations included lobectomy or bilobectomy in 88 (with 4 bronchoplastic procedures), pneumonectomy in 15, segmentectomy in 3, wedge resection in 16, and bronchial sleeve resection in 3 patients. One patient (0.7%) died in the perioperative period. Eighty-two patients (65%) had typical and 44 (35%) had atypical carcinoid tumors. Postoperative staging was complete for 113 of 126 patients (13 patients did not undergo lymphadenectomy): 90 patients had stage I disease, 6 had stage II, 15 had stage III, and 2 had stage IV disease. A typical subtype was stage I in 70 and more advanced (II-IV) in 5, whereas an atypical subtype was stage I in 20 and more advanced in 18 (P <.05). Mean follow-up was 99 +/- 73 months (range 6-282 months) during which 19 (15%) patients died (12 of recurrent disease). Recurrent tumor developed in 4 (5.5%) of 72 patients affected by typical subtypes and 8 (19.5%) of 41 by atypical subtypes with complete follow-up. Overall survival at 15 years was 74%; survival related to histologic type and nodal status at 15 years was significant (P <.05). CONCLUSIONS: Biologic behavior and prognosis for bronchial carcinoid tumors are better than for other lung cancers. Surgical treatment requires radical excision and lymph node sampling. Survival and long-term outcome are significantly related to the histologic type, nodal status, and pathologic stage