Central PACAP mediates the sympathetic effects of leptin in a tissue-specific manner.

We previously demonstrated that the peptidergic neurotransmitter pituitary adenylate cyclase-activating polypeptide (PACAP) affects the autonomic system and contributes to the control of metabolic and cardiovascular functions. Previous studies have demonstrated the importance of centrally-mediated sympathetic effects of leptin for obesity-related hypertension. Here we tested whether PACAP signaling in the brain is implicated in leptin-induced sympathetic excitation and appetite suppression. In anesthetized mice, intracerebroventricular (ICV) pre-treatment with PACAP6-38, an antagonist of the PACAP receptors (PAC1-R and VPAC2), inhibited the increase in white adipose tissue sympathetic nerve activity (WAT-SNA) produced by ICV leptin (2µg). In contrast, leptin-induced stimulation of renal sympathetic nerve activity (RSNA) was not affected by ICV pre-treatment with PACAP6-38. Moreover, in PACAP-deficient (Adcyap1-/-) mice, ICV leptin-induced WAT-SNA increase was impaired, whereas RSNA response was preserved. The reductions in food intake and body weight evoked by ICV leptin were attenuated in Adcyap1-/- mice. Our data suggest that hypothalamic PACAP signaling plays a key role in the control by leptin of feeding behavior and lipocatabolic sympathetic outflow, but spares the renal sympathetic traffic.

The frequency of high/moderate lipoprotein risk factor for coronary artery disease is significant in juvenile-onset systemic lupus erythematosus.

To determine the prevalence of dyslipoproteinemia on a large juvenile systemic lupus erythematosus (jSLE) cohort, we selected 40 patients after rigorous exclusion criteria. Lipoprotein levels were determinated after 12 hours fast and risk levels for CAD were defined by standards of the Brazilian Guidelines for dyslipoproteinemia according to US-NCEP. All individuals were under steroid therapy and chloroquine and 43% had active disease. Thirty patients (75%) had high-risk levels for CAD (23 isolated low HDL, while in seven subjects low HDL was associated to high TG in four, high LDL in one, high TG/LDL in one and high TC/LDL in one). Remarkably, overall analysis revealed that 85% patients were included in high/medium risk levels group (29% for TC, 29% for LDL, 88% for HDL, and 18% for TG) and these disturbances occured mainly in the first four years of disease. Unexpectedly, one-third of the patients presented two or more high/medium lipoprotein risk factors. Independently, active jSLE was associated to TG (OR = 3.2; P < 0.001) and had a tendency towards reduction on HDL (OR = 8.5; P = 0.056). Considering improvements on jSLE outcome, the increased frequency of high/medium lipoprotein risk levels for CAD reinforces the need of prevention measures in order to minimize deleterious effects of this disturbance.

Hepatocyte growth factor concentration in rat bile is affected by hepatic resection volume and external biliary drainage.

BACKGROUND/AIMS: Hepatocyte growth factor (HGF) concentrations in bile have been shown to be useful in the early assessment of liver function after hepatectomy. The aim of the present study is to prove the hypothesis that the level of bile HGF is proportional to the regeneration capacity of the liver using a rat model. METHODS: Blood and bile were sampled from rats who underwent 30 or 70% hepatectomy, with or without biliary drainage. HGF concentrations were determined using enzyme-linked immunosorbent assay. RESULTS: Liver regeneration was significantly suppressed after hepatectomy in the rats that underwent external biliary drainage. The bile HGF concentration was positively correlated with the resected liver volume within 24 h of hepatectomy, and HGF levels were markedly increased by external biliary drainage. The postoperative changes in plasma HGF were less dramatic. CONCLUSIONS: HGF appears to play an important role in liver regeneration. Bile HGF concentrations, unlike plasma HGF levels, are a good reflection of the hepatic biosynthesis of this growth factor. Increased concentrations of HGF in bile after external biliary drainage may reflect a compensatory response to the continuous loss of hepatocyte growth factor-rich fluid.

Active form of human hepatocyte growth factor is excreted into bile after hepatobiliary resection.

BACKGROUND/AIMS: We have shown that hepatocyte growth factor is excreted into bile after hepatectomy in patients with biliary tract carcinoma. However, it is not certain whether hepatocyte growth factor in bile is an active molecule or degradation products. METHODS: Bile was obtained from five patients after hepatobiliary resection. Bile hepatocyte growth factor was purified on a heparin-Sepharose column and subjected to Western blotting. It was also tested for growth-stimulating activity with rat primary cultured hepatocytes. Biles from 50 patients who underwent various types of hepatobiliary resections were examined with respect to hepatocyte growth factor by an enzyme-linked immunosorbent assay. RESULTS: Upon Western blotting following nonreducing electrophoresis, the purified bile hepatocyte growth factor showed an 85 kDa peptide corresponding to native hepatocyte growth factor. Under reducing conditions, it showed bands of a-subunit at 69 kDa and beta-subunit at 34 kDa with corresponding monoclonal antibodies. The purified bile hepatocyte growth factor stimulated the [3H]thymidine incorporation into primary cultured hepatocytes with a specific activity comparable to recombinant human hepatocyte growth factor. It was observed that the levels of bile hepatocyte growth factor increased after the various types of hepatobiliary resections, including bile duct resection without hepatectomy. CONCLUSIONS: The human bile obtained after hepatobiliary resection contains active hepatocyte growth factor that can stimulate hepatocyte growth. Bile hepatocyte growth factor increased not only in hepatectomy but in bile duct resection. These results suggest that the biliary tract system may play an important role in the production of bile hepatocyte growth factor.

VATS for complete dissection of LIMA in minimally invasive coronary artery bypass grafting.

BACKGROUND: The aim of this work is to report our initial experience with minimally invasive coronary artery bypass grafting, using video-assisted thoracic surgery (VATS) to facilitate the operation and provide complete dissection of the left internal mammary artery (LIMA). METHODS: Of 44 scheduled patients, 43 patients, 30 (69.8%) male, ranging in age from 31 to 83 years (60.8 +/- 12.0 years), with a severe lesion in the anterior descending artery, were operated upon. An 8-cm left anterior minithoracotomy was performed at the fourth intercostal space. Through this incision the optical device for video-assisted thoracic surgery as well as the surgical instruments were placed to provide complete LIMA dissection. This permits dissection until the subclavian region, allowing for anastomosis without tension or distortion. Bypass circulation was not used, and the cardiac rate was decreased with the use of intravenous beta-blockers. For LIMA-to-anterior descending artery anastomosis, proximal and distal tourniquets were used and 1.5 mg/kg of heparin was administered intravenously. RESULTS: Video-assisted thoracic surgery provided a complete dissection of LIMA. The 43 patients presented satisfactory postoperative progress, being released from the hospital between 2 and 12 days after their operation, with a mean of 4 days. The patients have remained asymptomatic during a period that ranged from 1 to 13 months (6.3 +/- 3.5 months). During the follow-up, there was one death as a result of stroke and pneumonia 2 months after the release from the hospital. CONCLUSIONS: The use of video-assisted thoracic surgery through thoracotomy allows the LIMA dissection without the necessity of other incisions. The procedure also permitted more ample dissection of LIMA when compared with minithoracotomy without video-assisted thoracic surgery.

[Minimally invasive myocardial bypass surgery using video-assisted thoracoscopy]. / Cirurgia de revascularização do miocárdio minimamente invasiva com utilização da videotoracoscopia.

PURPOSE: In order to associate the major benefits of the coronary artery bypass graft (CABG) with a less aggressive procedure minimally invasive coronary artery bypass graft (MICABG) has been utilized. The aim of the work is to report our initial experience with this technical approach, using video assisted thoracic surgery (VATS) to facilitate the operation. METHODS: Twenty-six patients, 19 males with ages from 44 to 83 years old, and having isolated lesion of the anterior descending artery were operated upon. Left anterior minithoracotomy of 8-10 cm was performed at the fourth intercostal space. Through this incision the optical device for VATS as well as the surgical instruments were placed in order to provide the complete left internal mammary artery (LIMA) dissection. Bypass circulation was not used and cardiac rate was decreased with the use of intravenous betablockers. For LIMA--anterior descending artery anastomosis, proximal and distal tourniquets were used and 1.5 mg/kg of heparin was intravenously administered. RESULTS: All patients presented satisfactory postoperative evolution, being discharged from the hospital at 72 h after surgery in the majority of the cases. There were delay in two patients healing of incisions and 25 patients have remained asymptomatic, with a mean in postoperative follow-up of four months. One patient died in the second postoperative month due to stroke. CONCLUSION: MICABG makes the surgery possible with better esthetic effect, lower cost and enables faster recovery than the conventional one. The use of VATS through the thoracotomy itself, allows the LIMA dissection without other incisions. It also permitted more ample dissection of the LIMA when compared to minithoracotomy without VATS.

Cirurgia de revascularização do miocárdio minimamente invasiva com utilização da videotoracoscopia / Minimally Invasive Myocardial Bypass Surgery Using Video-Assisted Thoracoscopy

PURPOSE: In order to associate the major benefits of the coronary artery bypass graft (CABG) with a less aggressive procedure minimally invasive coronary artery bypass graft (MICABG) has been utilized. The aim of the work is to report our initial experience with this technical approach, using video assisted thoracic surgery (VATS) to facilitate the operation. METHODS: Twenty-six patients, 19 males with ages from 44 to 83 years old, and having isolated lesion of the anterior descending artery were operated upon. Left anterior minithoracotomy of 8-10 cm was performed at the fourth intercostal space. Through this incision the optical device for VATS as well as the surgical instruments were placed in order to provide the complete left internal mammary artery (LIMA) dissection. Bypass circulation was not used and cardiac rate was decreased with the use of intravenous betablockers. For LIMA--anterior descending artery anastomosis, proximal and distal tourniquets were used and 1.5 mg/kg of heparin was intravenously administered. RESULTS: All patients presented satisfactory postoperative evolution, being discharged from the hospital at 72 h after surgery in the majority of the cases. There were delay in two patients healing of incisions and 25 patients have remained asymptomatic, with a mean in postoperative follow-up of four months. One patient died in the second postoperative month due to stroke. CONCLUSION: MICABG makes the surgery possible with better esthetic effect, lower cost and enables faster recovery than the conventional one. The use of VATS through the thoracotomy itself, allows the LIMA dissection without other incisions. It also permitted more ample dissection of the LIMA when compared to minithoracotomy without VATS.