Statins reduce levels of metalloproteinases in patients with carotid occlusive disease.

AIM: Pharmaceutical stabilization of an unstable low-grade carotid artery stenosis delays surgery and improve outcome. Statins can be used to reduce intimal media thickness. Our aim was to determine the clinical and biological effects of rosuvastatin on plaque stabilization or regression. METHODS: Forty-two consecutive male patients presenting with an asymptomatic internal carotid artery plaque uniformly anechogenic (group 1) 40-50% lumen diameter reduction formed the basis of the study. A group of 35 patients affected with a uniformly echogenic carotid artery stenosis (40-50%) served as control (group 2). Patients were followed-up every 8-month for 2 years with B-mode ultrasonography and color imaging. A computed tomography angiography (CTA) was performed before the initiation of the study period and at the end to confirm plaque characteristics and the degree of stenosis. Ticlopidine (250 mg/day) and rosuvastatin (10 mg/day) were administered. One blood sample was drawn at every control to assess the release of matrix metallopoteinases (MMPs)-1, -2, -3, -9, tissue inhibitors of metalloproteinases (TIMPs)-1 and -2. RESULTS: After the administration of rosuvastatin plasma level of MMP-1, -2, -3 and -9 significantly decreased in both groups (P<0.001). Conversely, plasma level of TIMP-1 and -2 significantly increased in both groups (P<0.001). B-mode ultrasonography and color imaging and CTA failed to demonstrate a stabilization or regression of uniformly anehogenic carotid plaque during follow-up. CONCLUSION: Rosuvastatin decreases the plasma level of MMPs and increases those of TIMPs. However, neither progression nor stabilization of low-grade unstable carotid plaques was seen.

Determinants of health-related quality of life in morbid obese candidates to gastric banding.

OBJECTIVE: To analyse determinants of self reported health-related quality of life (HR-QoL) in morbid obese patients candidates to laparoscopic adjustable gastric banding (LAGB). METHODS: Determinants of HR-QoL were investigated in 383 morbid obese patients (82 M and 301 F) with BMI≥40 kg/m² (BMI≥35 kg/m² if complicated obesity) and age 18-60 years. HR-QoL was determined with the SF-36 questionnaire. Determinants of the two summary measures of SF-36 (physical component and mental component) were analysed by stepwise multiple linear regression analysis with age, BMI, physical comorbidites, mental comorbidites and eating behaviour disorders as independent variables. Physical comorbities (diabetes, hypertension, hypertriglyceridemia, low HDL, sleep apnea and osteoarthritis) were coded as present or absent on the basis of simple diagnostic clinical criteria; mental comorbidities (depression) and eating behaviour disorders (binge eating, sweet eating and nibbling) on the basis of an unstructured clinical interview. RESULTS: Mean age was 38.8±10.2 years and mean BMI was 41.5±5.4 kg/m². Scores in the eight SF-36 subscales were lower in women than in men and lower than in the general Italian population. However, 18.4-43.5% of the participants had HR-QoL levels above the normative values, depending on the scale. In both genders, low scores in the mental component of the SF-36 were associated to the presence of depression and eating behaviour disorders and not to physical comorbidities or BMI levels. Low physical self-perceived well being was associated to high BMI levels in men and to depression, hypertension and hypertriglyceridemia in women. CONCLUSION: HR-QoL was poor in morbid obese candidates to LAGB, particularly in women, and was negatively affected more by mental comorbidites and eating behaviour disorders than by physical comorbidities or BMI levels.

MMP and TIMP alterations in asymptomatic and symptomatic severe recurrent carotid artery stenosis.

OBJECTIVES: This study aimed to determine whether the plasma levels of matrix metalloproteinases (MMPs)-2 and -9 and their specific inhibitors (tissue inhibitors of metalloproteinases (TIMPs-1 and -2)) were altered in patients with symptomatic and asymptomatic, severe, recurrent carotid artery stenosis. PATIENTS: Fifty-two patients (out of a total of 621) who had undergone successful carotid artery endarterectomy (CEA) between 1999 and 2003 and developed recurrent carotid artery stenosis (>/=70%) were included in the study. Restenosis was symptomatic in 23 patients and asymptomatic in 29 patients. METHODS: Recurrent carotid artery stenosis was classified based on presentation, and as early-intermediate (6 months to 3 years) or late (>3 years). A detailed clinical history was taken and two blood samples were drawn from each patient to determine plasma levels of MMPs and TIMPs along with other biological parameters. Recurrent stenosis was confirmed with computed tomographic angiography. RESULTS: Patients with symptomatic restenosis had significantly (p<0.001) higher active MMP-2 and -9 plasma values and significantly (p<0.001) lower TIMP-1 and -2 plasma values when compared to patients with asymptomatic restenosis. Plasma concentrations of active MMPs were higher and TIMPs lower in patients affected with late recurrent stenosis as compared to early-intermediate restenosis (p<0.001). No differences were recorded in latent MMP plasma values. Multivariate analysis showed that active MMP-2 and -9 were independent predictors of late recurrent carotid artery stenosis (p<0.03 and p<0.001, respectively). CONCLUSIONS: Higher plasma concentrations of active MMP-2 and -9 were associated with an increased risk of carotid restenosis with plaque recurrence.

Carcinoid of the vermiform appendix. Description of three clinical cases and review of the literature.

Carcinoids of the appendix represent a separate class of tumours with characteristics that vary between benign (adenomas) and malignant (carcinomas) neoplasias. A recent nomenclature identifies them as diffuse neuroendocrine system (DNS) and/or, parallely, as neuroendocrine tumours (NET): the gastroenteric tract is the site of about 64.3% of carcinoids, followed by the respiratory tract with 25.3%. Among the gastrointestinals, tumour of the small intestine is the one with the highest incidence with 28.5%, followed by the appendix with 4.77%, the rectum with 13.6% and the stomach with 4.6%. Carcinoid of the colon has an incidence of 8.62%, with the caecum which alone represents 34.5% of colic localisations. The 3 cases described are an example of the behavioural unpredictability of intestinal carcinoids. The first case is that of a female patient in whom the primary tumour was only discovered after liver metastasis was documented. The second case regards a girl who, at admission, presented a picture of acute abdomen with the symptomatological characteristics of acute appendicitis. She was submitted to an appendicectomy. Subsequent investigations carried out in the postoperative period documented the presence of liver metastasis at the V and VI liver segments. The last case, similar to the second from certain points of view, shows the need to carry out a right hemicolectomy with removal of locoregional lymphnodes in the event of an appendicular carcinoid >2 cm. Both laboratory and instrumental examinations contribute to the diagnosis of intestinal carcinoid. The main laboratory examinations are based on the measurement of serotonin and urinary 5-hydroxy-indolacetic acid. First level instrumental examinations for the diagnosis of intestinal carcinoid are represented by CT with and without contrast medium, diagnostic endoscopy and, to better highlight the presence of locoregional metastases, scintigraphy with octreotide and PET. An alternative treatment of liver metastases other than surgery is most certainly chemoembolisation. This latter treatment has also proved very effective as a neoadjuvant treatment for liver metastases before subjecting the patient to liver resection. Treatment with somatostatin, on the other hand, proved effective in controlling tumour secretion, so attenuating the inconveniences of carcinoid syndrome.

Obese teenagers treated by Lap-Band System: the Italian experience.

BACKGROUND: Little is known about obesity surgery in young and adolescent patients. The aim of this study is to evaluate results of laparoscopic adjustable gastric banding in obese teenagers. METHODS: Patients < or = 19 years old selected from the database of the Italian Collaborative Study Group for Lap-Band were analyzed according to mortality, comorbidities, laparotomic conversion, intra- and postoperative complications, body mass index (BMI), and % excess weight loss (EWL) at different times of follow-up. Data were expressed as mean +/- SD. RESULTS: Fifty-eight (1.5%) of 3813 patients who underwent operation with the Lap-Band System were < or = 19 years old: 47F/11M; mean age, 17.96 +/- 0.99 years (range, 15-19); mean BMI, 46.1 +/- 6.31 Kg/m2 (range, 34.9 - 69.25); mean % excess weight, 86.4 +/- 27.1 (range, 34 - 226.53). Sixteen (27.5%) of the 58 patients were superobese (BMI > or = 50). In 27/58 (46.5%) patients, 1 or more comorbidities were diagnosed. Mortality was absent. Laparotomic conversion was necessary in 1 patient with gastric perforation on the anterior wall. Overall postoperative complications occurred in 6/58 (10.3%). The band was removed in 6/58 (10.3%) patients for gastric erosion (3 patients), psychologic, intolerance (2 patients), and in the remaining patient was converted 2 years after surgery (BMI 31) to gastric bypass or gastric pouch dilatation. Patient follow-up at 1, 3, 5, and 7 years was 48/52 (92.3%), 37/42 (88.1%), 25/33 (75.7%), and 10/10, respectively. At these times, mean BMI was 35.9 +/- 8.4, 37.8 +/- 11.27, 34.9 +/- 12.2, and 29.7 +/- 5.2 Kg/m2. Mean %EWL at the same time was 45.6 +/- 29.6, 39.7 +/- 29.8, 43.7 +/- 38.1, and 55.6 +/- 29.2. Five/25 (20%) patients had < or = 25% EWL at 5 years follow-up, while none of the 10 patients subject to follow-up at 7 years had < or = 25% EWL. CONCLUSIONS: Lap-Band System is an interesting option for teenagers suffering obesity and its related comorbidities, which deserves further investigation.

Basic fibroblast growth factor mediates carotid plaque instability through metalloproteinase-2 and -9 expression.

OBJECTIVE(S): We hypothesized that basic fibroblast growth factor (bFGF) may exert a role in carotid plaque instability by regulating the expression of matrix metalloproteinases (MMP). METHODS: Plaques obtained from 40 consecutive patients undergoing carotid endarterectomy were preoperatively classified as soft or hard. Serum bFGF was pre- and postoperatively measured. The release of MMP-2 and MMP-9 in the blood serum, and the activity, production and expression in the carotid specimens was analyzed. Specific anti-bFGF inhibition tests were performed in vitro on human umbilical artery smooth muscle cells (HUASMC) to evaluate the role of bFGF in the activity, production and expression of MMP-2 and -9. RESULTS: Twenty-one (53%) patients had a soft carotid plaque and 19 (48%) a hard plaque. Preoperative bFGF serum levels were higher in patients with soft plaques [soft=34 (28-39) pg/mL and hard=20 (17-22) pg/mL-p<0.001] and postoperatively returned to normal values (when compared to 10 healthy volunteers). The serum levels of MMP-2 in patients' with soft plaques were higher than those in patients' with hard plaques [soft=1222 (1190-1252) ng/mL and hard=748 (656-793)ng/mL-p<0.0001]. MMP-9 serum values were 26 (22-29) ng/mL for soft plaques and 18 (15-21) ng/mL for hard plaques (p<0.0001). We found increased activity, production and expression of MMP-2 and -9 in soft plaques compared to hard plaques (p<0.001). In vitro inhibition tests on HUASMC showed the direct influence of bFGF on the activity, production and expression of MMP-2 and -9 (p<0.001). CONCLUSIONS: bFGF seems to exert a key role in carotid plaque instability regulating the activity, production and expression of MMP thus altering the physiologic homeostasis of the carotid plaque.

Italian Group for Lap-Band System: results of multicenter study on patients with BMI < or =35 kg/m2.

BACKGROUND: The Lap-Band System is the most common bariatric operation world-wide. Current selection criteria do not include patients with BMI < or = 35. We report the Italian multicentre experience with BMI < or = 35 kg/m(2) over the last 5 years. PATIENTS AND METHODS: Data were obtained from 27 centres involved in the Italian Collaborative Study Group for Lap-Band System. Detailed information was collected on a specially created electronic data sheet (MS Access 2000) on patients operated in Italy since January 1996. Items regarding patients with BMI < or = 35 were selected. Data were expressed as mean +/- SD except as otherwise indicated. RESULTS: 225 (6.8%) out of 3,319 Lap-Band patients were recruited from the data-base. 15 patients, previously submitted to another bariatric procedure (BIB =14; VBG= 1) were excluded. 210 patients were eligible for study (34M/176F, mean age 38.19+/-11.8, range 17-66 years, mean BMI 33.9+/-1.1, range 25.1-35 kg/m(2), mean excess weight 29.5+/-7.1, range 8-41). 199 comorbidities were diagnosed preoperatively in 55/210 patients (26.2%). 1 patient (0.4%) (35 F) died 20 months postoperatively from sepsis following perforation of dilated gastric pouch. There were no conversions to laparotomy. Postoperative complications presented in 17/210 patients (8.1%). Follow-up was obtained at 6, 12, 24, 36, 48 and 60 months. At these time periods, mean BMI was 31.1+/-2.15, 29.7+/-2.19, 28.7+/-3.8, 26.7+/-4.3, 27.9+/-3.2, and 28.2+/-0.9 kg/m(2) respectively. Co-morbidities completely resolved 1 year postoperatively in 49/55 patients (89.1%). At 60 months follow-up, only 1 patient (0.4%) has a BMI >30. CONCLUSIONS: Although surgical indications for BMI < or = 35 remain questionable, the Lap-Band in this study demonstrated that all but 1 patient achieved normal weight, and most lost their co-morbidities with a very low mortality rate.

The Italian Group for LAP-BAND: predictive value of initial body mass index for weight loss after 5 years of follow-up.

BACKGROUND: Laparoscopic of the LAP-BAND System placement stage of obesity is a safe operation, but its indication in terms of stage of obesity is controversial. The aim of this study was to evaluate the 5 years stage of obesity results for weight loss in patients with varying preoperative ranges of body mass index (BMI). METHODS: Data were obtained from the Italian Collaborative Study Group for LAP-BAND System (GILB) registry. Detailed information was collected on a specifically created database (MS Access 2000) for patients operated on in Italy from January 1996 to 2003. Patients operated on between January 1996 and December 1997 were allocated to four groups according to preoperative BMI range: 30-39.9 kg/m(2) (group A), 40-49.9 kg/m(2) (group B), 50-59.9 kg/m(2) (group C), and =60 kg/m(2) (group D) percent estimated weight loss respectively. Postoperative complications, mortality, BMI, BMI loss, and (%EWL) were considered in each group. Data are expressed as mean +/- SD, except as otherwise indicated. Statistical analysis was done by means of Fisher's exact test, and p < 0.05 was considered significant. RESULTS: After 5 years from LAP-BAND System surgery, 573 of 3,562 patients were eligible for the study. One hundred fifty-five of 573 (27.0%) were lost to follow-up, 24 of 418 (5.7%) underwent band removal due to complications (gastric pouch dilation, band erosion), eight of 418 (1.9%) were converted to other bariatric procedures, five of 418 (1.2%) died of causes not related to the operation or the band, and 381 of 573 (66.5%) were available for follow-up. Based on 96, 214, 64, and seven patients their preoperative BMI, Were allocated to groups A, B, C, and D, respectively. At time of follow-up mean BMI was 27.5 +/- 5.2 in group A, 31.6 +/- 4.7 in group B, 37.6 +/- 17.3 in group C, and 41.4 +/- 6.9 kg/m(2) in group D. Mean BMI loss was 9.8 +/- 5.4, 12.9 +/- 5.2, 15.8 +/- 8.1, and 23.2 +/- 4.9 kg/m(2), respectively, in groups A, B, C, and D. Mean %EWL at the same time was 54.6 +/- 32.3 in group A, 54.1 +/- 17.2 in group B, 51.6 +/- 35 in group C, and 59.l +/- 17.1 in group D. CONCLUSION: Initial BMI in this series did not correlate with %EWL 5 years after the operation. In fact %EWL was almost the same in each group, independent of preoperative weight. Initial BMI was an accurate indicator of the results obtained 5 years after LAP-BAND in group C (50-59.9 kg/m(2)) and D (=60 kg/m(2)) patients, who remained morbidly obese despite their %EWL.

Lap Band adjustable gastric banding system: the Italian experience with 1863 patients operated on 6 years.

BACKGROUND: The Lap Band system procedure is currently the most common bariatric surgical procedure worldwide. This is an interim report of the experience of the 27 Italian centers participating in the national collaborative study group for Lap Band (GILB). METHODS: An electronic database was specifically created. It was mailed and e-mailed to all of the surgeons now performing the laparoscopic gastric banding operation in Italy. RESULTS: Beginning in January 1996, 1893 patients were recruited for the study. There were 1534 women and 359 men with a mean body mass index (BMI) of (range 30.4-83.6) and a mean age of 37.8 +/- 10.9 years (range; 17-74). The mortality rate has been 0.53% (n = 10), mainly due to cardiovascular complications (myocardial infarction, pulmonary embolism). The laparotomic conversion rate has been 3.1% (59/1893) and was higher in superobese patients (BMI>50) than in to morbidly obese patients (BMI <50) (p <0.05). Postoperative complications occurred in 193 patients (10.2%), including tube port failure (n = 79; 40.9%), gastric pouch dilation (GPD) (n = 93; 48.9%), and gastric erosion (n = 21, 10.8%). Most GPD (65.5%) occurred during the first 50 patients treated at each center. The incidence of GPD decreased as the surgeons acquired more experience. Surgery for complications was often performed by laparoscopic access, rarely via laparotomy. No death was recorded as a consequence of surgery to treat complications. Weight loss has been evaluated at the following intervals: 6, 12, 24, 36, 48, 60, and 72 months, with BMI 37.9, 33.7, 34.8, 34.1, 32.7, 34.8, and 32. CONCLUSIONS: The Lap Band system procedure has a very low mortality rate and a low morbidity rate and it yields satisfactory weight loss. Surgery for complications can be performed safely via laparoscopic access.

Abnormal esophageal acid exposure is common in morbidly obese patients and improves after a successful Lap-band system implantation.

BACKGROUND: The relation between gastro-esophageal reflux disease (GERD) and obesity is controversial. The laparoscopic adjustable gastric band (LAGB) procedure is effective for morbid obesity. Its indication in the presence of GERD, however, is still debated. This study aimed to investigate esophageal symptoms, motility patterns, and acid exposure in morbidly obese patients before and after LAGB placement. METHOD: For this study, 43 consecutive obese patients were investigated by a standardized symptoms questionnaire, stationary manometry and 24-h ambulatory pH-metry, and 16 patients with abnormal esophageal acid exposure were reevaluated 18 months after LAGB placement. RESULTS: Symptom scores and abnormal esophageal acid exposure were found to be significantly higher, Lower Esophageal Sphincter (LOS) pressure was significantly lower in obese patients than in control subjects. After LAGB, esophageal acid exposure was significantly reduced in all but two patients, who presented with proximal of gastric pouch dilation. CONCLUSIONS: There is a high prevalence of GERD in the obese population. Uncomplicated LAGB placement reduces the amount of acid in these patients with abnormal esophageal acid exposure.

Results of the Italian multicenter study on 239 super-obese patients treated by adjustable gastric banding.

BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) is the most common bariatric operation. This study is a retrospective analysis of the multicenter Italian experience in patients with BMI > 50 over the last 4 years. METHODS: An electronic data sheet made for LAGB-operated patients since January 1996, was mailed and e-mailed to all surgeons involved in this kind of procedure in Italy. Items regarding patients with BMI > 50 were selected. Analysis used Fisher's exact test and logarithmic regression analysis (P < 0.05 significant). Data were expressed as mean +/- SD. RESULTS: 239 patients (13.3%), out of 1,797 Lap-Band operated patients entered the study (179F / 60M), with mean age 37.6 +/- 11.3 years (19-69) and mean BMI 54.6 +/- 4.8 (50.1-83.6). Laparotomic conversion rate was 5.4% (44/239). Postoperative complications occurred in 24 / 239 patients (9.0%). Follow-up was obtained in 218 / 218, 198 / 198, 121 /147, 75 / 93, 30 / 38 LAGB patients at 6,12, 24, 36, and 48 months respectively. At these time periods, mean BMI was 46.7, 43.9, 42.2, 41.9, and 39.3 kg/m2. At the same intervals, mean %EWL was 24.1, 34.1, 38.8, 38.9, and 52.9%. The number of patients with < 25% EWL at 12, 24, 36, and 48 months follow-up were 34, 10, 4, and 0. Serious co-morbidities (189 in 124 of 239, 57%) had completely resolved 1 year postoperatively in 74 / 124 of the patients (59.6%). CONCLUSION: Although super-obese patients following the LAGB remain obese with BMI > 35, in the short-term most lose their co-morbidities, with a very low morbidity and mortality rate.

Bimodal concentration-dependent effect of thrombin on endothelial cell proliferation and growth factor release in culture.

BACKGROUND: The role of thrombin in the stimulation of endothelial cell (EC) proliferation is controversial. The aim of this study was to investigate if thrombin regulates cell proliferation and production of platelet-derived growth factor (PDGF), bovine fibroblast growth factor (bFGF), and transforming growth factor beta(1) (TGF-beta(1)) by bovine aortic ECs. METHODS: ECs, obtained from thoracic aortas of calves, were stimulated with thrombin at various concentrations (from 0.05 to 1.0 IU/ml) in serum free culture. Mitogenic activity of thrombin on ECs was determined by tritiated thymidine uptake. The release of PDGF, bFGF, and TGF-beta(1) was assessed by ELISA. PDGF release was confirmed by Western blot and bFGF and TGF-beta(1) mRNA expression was determined by polymerase chain reaction (PCR). RESULTS: Thrombin at high concentrations did not cause any increase in EC proliferation after 72 h of culture and induced inhibition of EC proliferation after 96 h and 8 days of culture. It induced a decrease in PDGF release and an increase in TGF-beta(1) release. Thrombin at low concentrations induced a significant increase in EC proliferation at 72 h, 96 h, and 8 days of culture. It induced an increase in PDGF release and a decrease in TGF-beta(1) release. bFGF release was higher than control at all thrombin concentrations. These data were confirmed by Western blot and PCR studies. CONCLUSIONS: Thrombin regulates EC growth through the inhibition of EC proliferation at high concentrations and through the stimulation of EC proliferation at low physiological concentrations. EC proliferation is partially mediated by autocrine production of PDGF, bFGF, and TGF-beta(1).

Laparoscopic Italian experience with the Lap-Band.

BACKGROUND: An increasing number of surgeons with different levels of experience with laparoscopic surgery and open obesity surgery have started to perform laparoscopic implantation of the Lap-Band. METHODS: An electronic patient data sheet was created and was mailed and e-mailed to all surgeons performing laparoscopic adjustable silicone gastric banding (LASGB) in Italy. Patients were recruited since January 1996. Data on 1,265 Lap-Band System operated patients (258 M/1,007 F; mean BMI 44.1, range 27.0-78.1; mean age 38, range 17-74 years) were collected from 23 surgeons performing this operation. RESULTS: Intra-operative mortality was absent. Post-operative mortality was 0.55% (7 patients) for causes not specifically related to LASGB implantation. The laparotomic conversion rate was 1.7% (22 patients). LASGB related complications occurred in 143 patients (11.3%). Pouch dilatation was diagnosed in 65 (5.2%), and 28 (2.2%) of these underwent re-operation. Band erosion was observed in 24 patients (1.9%). Port or connecting tube-port complications occurred in 54 patients (4.2%), 12 of whom required revision under general anesthesia. Follow-up was obtained at 6, 12, 18, 24, 36 and 48 months, and mean BMI was respectively 38.4, 35.1, 33.1, 30.2, 32.1 and 31.5. The percentage of patients observed at each follow-up was > 60%. There was no intra-operative mortality and no complication-related mortality, with acceptable weight loss. CONCLUSION: The LASGB operation is safe and effective, and deserves wider use for treatment of morbid obesity.

Conversion of Lap-Band to gastric bypass for dilated gastric pouch.

An 18-year-old female who had undergone a laparoscopic adjustable gastic banding developed several episodes of gastric pouch dilatation (GPD), treated conservatively. The last GPD (31 months after Lap-Band placement) involved the lesser curvature of the stomach and was refractory to medical treatment. Conversion to an open gastric bypass was performed. Gastric bypass is an option in the case of Lap-Band failure.

Nicotine reorganizes cytoskeleton of vascular endothelial cell through platelet-derived growth factor BB.

BACKGROUND: Cigarette smoking has been directly linked to atherosclerosis formation and vascular graft failures but the role of nicotine in these processes is not yet completely understood. We investigated the release of platelet-derived growth factor BB (PDGF BB) by the bovine aortic endothelial cell (EC) after nicotine administration at concentrations similar to those found in plasma of active and passive smokers and the role of PDGF BB, autocrinally released, in EC cytoskeletal modification. METHODS: EC were stimulated in a serum-free medium for 72 h with (-)-nicotine (from 6 x 10(-4) to 6 x 10(-8) M). The release of PDGF BB was assessed by inhibition antibody-binding assay and confirmed by Western blotting. Mitogenic activity of nicotine on EC was also determined. The EC cytoskeleton was studied with specific antibodies anti-alpha-actin fibers and anti-vimentin and the modification induced by PDGF BB was assessed by blocking PDGF BB activity with specific antibodies. RESULTS: The greatest PDGF BB release was noted at a (-)-nicotine concentration of 6 x 10(-6) M (P < 0.001). The addition of antibody anti-PDGF BB to EC exposed to (-)-nicotine decreased tritiated thymidine uptake by 20% (P < 0.001). EC exposed to (-)-nicotine concentrations of 6 x 10(-6) and 6 x 10(-8) M had a significant alteration in the expression of alpha-actin fibers and vimentin as compared with control. Administration of the antibody anti-PDGF BB in the culture medium reversed cytoskeletal alteration. CONCLUSIONS: Nicotine enhanced the release of PDGF BB by EC which in turn caused an alteration in cytoskeletal organization.

Nicotine-induced smooth muscle cell proliferation is mediated through bFGF and TGF-beta 1.

BACKGROUND: Cigarette smoking influences and enhances the development of atherosclerosis. We investigated if nicotine, an important constituent of cigarette smoking, has a stimulatory effect on bovine smooth muscle cell proliferation in vitro through the mediation of bFGF and TGF-beta 1. METHODS: Bovine aortic smooth muscle cells (SMC) were stimulated with (-)-nicotine at various concentrations ranging from 6 x 10(-4) mol/L to 6 x 10(-8) mol/L. SMC viability and count were assessed. The presence of bFGF and TGF-beta 1 in serum-free conditioned media was determined by the inhibition antibody-binding assay, and the mitogenic activity of (-)-nicotine on SMC was analyzed by the 3H-thymidine uptake. Polymerase chain reaction was used to study the expression of bFGF and TGF-beta 1. RESULTS: The bFGF release after (-)-nicotine stimulation was greater than in the controls, whereas TGF-beta 1 release was lower. The greatest mitogenic activity was found at a (-)-nicotine concentration of 6 x 10(-6) mol/L. The addition of monoclonal antibody anti-bFGF decreased the 3H-thymidine uptake of SMC exposed to (-)-nicotine, whereas the addition of monoclonal antibody anti-TGF-beta 1 increased the 3H-thymidine uptake of stimulated SMC. bFGF mRNA expression was significantly higher in SMC exposed to (-)-nicotine than in the controls, but TGF-beta 1 mRNA expression was significantly lower in SMC exposed to 6 x 10(-6) mol/L (-)-nicotine than in SMC treated with the other concentrations of (-)-nicotine and in controls. CONCLUSIONS: Nicotine is a potent regulator of bFGF and TGF-beta 1 production and release by aortic SMC, and it seems to play an important role in the development and progression of atherosclerosis and neointimal fibrous hyperplasia.

Nicotine induces platelet-derived growth factor release and cytoskeletal alteration in aortic smooth muscle cells.

BACKGROUND: Cigarette smoking is implicated in atherosclerotic plaque formation, but the role of nicotine in this process is not completely understood. The release of platelet-derived growth factor (PDGF) by the bovine aortic smooth muscle cell (SMC) after nicotine administration at a concentration similar to that ingested by active and passive smokers and the role of PDGF in SMC cytoskeletal modification were studied. METHODS: SMC, harvested with enzymatic digestion from calf aorta, were stimulated in a serum-free medium for 72 hours with (-)-nicotine (from 6 x 10(-4) mol/L to 6 x 10(-8) mol/L). The release of PDGF was assessed by inhibition antibody-binding assay and confirmed by Western blotting. Mitogenic activity of nicotine on SMCs was also determined. The SMC cytoskeleton was studied with specific antibodies anti-alpha-actin fibers, anti-vimentin, and anti-beta-tubulin, and the modification induced by PDGF was assessed by blocking PDGF activity with specific antibodies. RESULTS: The greatest PDGF release (1.24 +/- 0.14 ng/10(4) cells vs control 0.43 +/- 0.07 ng/10(4) cells) was noted at a (-)-nicotine concentration of 6 x 10(-7) mol/L (P < .001). The addition of monoclonal antibody anti-PDGF decreased the tritiated thymidine uptake of SMCs exposed to (-)-nicotine compared with the control (29% vs 5%-P < .001). SMCs exposed to (-)-nicotine concentration of 6 x 10(-7) mol/L and 6 x 10(-8) mol/L had a significant alteration in the expression of alpha-actin fibers, vimentin, and beta-tubulin compared with control. The administration of antibody anti-PDGF in the culture medium reversed cytoskeletal alteration. CONCLUSIONS: Nicotine enhanced the release of platelet-derived growth, which in turn caused an alteration in cytoskeletal organization.

Chylous reflux pathologies: diagnosis and microsurgical treatment.

BACKGROUND: This article aims to make a contribution to the present knowledge of the diagnosis and therapy of chylous reflux pathologies, based largely on the authors' clinical experience in the microsurgical treatment of these disorders. METHODS: In 47 patients affected by chylostatic disorders the diagnosis was based on the clinical history, physical examination, lymphoscintigraphy, lymphography, ultrasound, CT scanning and lymphangio-MR. In cases of chylous reflux towards the external genitalia or the lower limbs, the puncture of one of the lymphostatic verrucae which may be part of the symptomatology, can be sufficient for the clinical diagnosis. If patients suffer from hypoproteinaemia and/or an intestinal malabsorption syndrome, this should be dealt with to ensure them at least temporary metabolic compensation before surgical treatment, if any. In patients affected by chylous ascites, antigravitational ligatures of incompetent collectors, sometimes associated with lymphovenous shunts, can be a therapeutic solution. RESULTS: We have found that CO2 laser irradiation at very low power achieved full section closure of lymphatic and chylous vessels as complete as if they had been tied. In the case of chyloedema of the external genitalia and of/or the lower limbs, reductive plastic treatment completes the result after antigravitational ligatures and derivative microsurgery. CONCLUSIONS: A laser-microsurgical technique used to manage chylous reflux pathologies achieved positive and permanent results, especially after an accurate preoperative diagnostic study to determine the site and nature of the lymphatic and chylous leakage and associated disorders.

Nicotine regulates basic fibroblastic growth factor and transforming growth factor beta1 production in endothelial cells.

Nicotine, a constituent of cigarette smoking, may induce atherosclerosis through the production of growth factors. The pattern of bFGF and TGF beta1 production and release by bovine aortic endothelial cells (EC) stimulated with nicotine (from 6 x 10(-4) to 6 x 10(-8) M) was studied. EC viability and count were assessed. The presence of bFGF and TGF beta1 in serum-free conditioned media was determined by the inhibition antibody-binding assay and Western blot analysis. Mitogenic activity of nicotine on EC was also determined. Polymerase chain reaction (PCR) was used to study the expression of bFGF and TGF beta1. The bFGF release after nicotine stimulation was greater than controls, whereas TGF beta1 release was lower. At a nicotine concentration of 6 x 10(-6) M we noted the greatest mitogenic activity. The addition of monoclonal antibody anti-bFGF decreased the tritiated thymidine uptake of EC exposed to nicotine but the addition of monoclonal antibody anti-TGF beta1 had no significant effect. bFGF mRNA expression was significantly higher in EC exposed to nicotine than in controls, whereas TGF beta1 mRNA expression was not modified. From these data we concluded that nicotine regulates bFGF production and release and TGF beta1 release and may have a key role in the development and progression of atherosclerosis.