Aspirin increases CD36, SR-BI, and ABCA1 expression in human THP-1 macrophages

OBJECTIVE: CD36 is a receptor, whose expression increases during the differentiation of monocytes to macrophages, playing a key role in the phagocytosis of apoptotic cells and in the formation of foam cells during atherosclerosis. Recently, it has been described that ligands of PPARgamma induce CD36 expression and inhibit cyclooxygenase expression in macrophages. Our aim was to study whether the reduction of endogenous prostaglandin production could modify CD36 expression in macrophages and to outline the potential mechanism. METHODS AND RESULTS: CD36 expression was measured by flow cytometry in THP-1 cells differentiated to macrophages that had been incubated with aspirin (ASA) alone or in combination with PGE(2), sulprostone (EP1/EP3 agonist), butaprost (EP2 agonist,) and PGE1 alcohol (EP2/EP4 agonist). Aspirin induced CD36 expression. Only PGE(2) and PGE1 alcohol completely abolished CD36 induction by aspirin, whereas butaprost strongly reduced it. BADGE (a PPARgamma antagonist) or diclofenac (a PPARgamma antagonist and a cyclooxygenase inhibitor) in aspirin-incubated cells did not reduce CD36 induction. On the other hand, aspirin also induced the expression of SR-BI and ABCA1, an HDL receptor and an HDL formation-related protein, respectively. CONCLUSIONS: Aspirin produces an increase of CD36 expression in THP-1 macrophages by a PGE(2)-dependent mechanism. The PGE(2) receptors implicated in CD36 modulation by ASA are the EP2/EP4 subtypes. Further, we provide evidence of SR-BI and ABCA1 induction by aspirin treatment.     

Anatomical basis for nerve-sparing radical hysterectomy: immunohistochemical study of the pelvic autonomic nerves

BACKGROUND: Autonomic nerve damage plays a crucial role in the etiology of bladder dysfunction, sexual dysfunction, and colorectal motility disorders that occur after radical hysterectomy. We investigated the extent and nature of nerve damage in conventional and nerve-sparing radical hysterectomy. METHODS: Macroscopical disruption of nerves was assessed through anatomical dissection after conventional and nerve-sparing surgery on five fixed and one fresh cadaver. Immunohistochemical analysis of surgical margins was performed to confirm nerve damage using a general nerve marker (S100) and a sympathetic nerve marker (anti-tyrosine hydroxylase) within sections of biopsies. RESULTS: Macroscopical dissection showed that in the conventional procedure, transsection of the uterosacral ligaments resulted in disruption of the major part of the hypogastric nerve. After nerve-sparing surgery, only the medial branches of the hypogastric nerve appeared disrupted. Division of the cardinal ligaments in the conventional procedure identified the inferior hypogastric plexus running into the most posterior border of the surgical margin. The anterior part of the plexus was disrupted. Dissection of the nerves after the nerve-sparing procedure showed that this anterior part of the plexus was not involved in the surgical dissection line. Dissection of the vesicouterine ligament disrupted only small nerves on the medial border of the inferior hypogastric plexus in both techniques. Microscopical evaluation of the surgical margins confirmed the macroscopical findings. CONCLUSION: Conventional radical hysterectomy results in disruption of a substantial part of the pelvic autonomic nerves. The nerve-sparing modification leads to macroscopic reduction in nerve disruption which is substantiated by microscopical evaluation of surgical margins.     

Impaired visuospatial recognition memory but normal object novelty detection and relative familiarity judgments in adult mice expressing the APPswe Alzheimer's disease mutation

The present study examined the effects of a human APPswe mutation on object recognition memory in adult Tg2576 mice. The results showed that 14-month old Tg2576 mice were able to detect object novelty as well as control mice, even with delays of up to 24 hr. In addition, transgenic mice showed a normal recency effect and explored the most recently encountered object significantly less than an object encountered earlier in a trial. However, adult Tg2576 mice showed impairments in detecting a change in the relative positions of an array of familiar objects. The results suggest that the formation of representations involving a combination of object identity and spatial information are particularly sensitive to amyloid pathology in adult APPswe mutant mice.     

Laparoscopic surgery in patients with sporadic and multiple insulinomas associated with multiple endocrine neoplasia type 1

There have recently been reports of a limited number of laparoscopic procedures in patients with clinically manifest hyperinsulinism. However, the precise role of laparoscopy remains unknown. Between January 1998 and September 2003, 11 consecutive patients (10 women and 1 man; mean age, 40 years; age range, 22–66 years) with sporadic insulinoma and two female patients (25 and 40 years old) with multiple insulinomas associated with multiple endocrine neoplasia type 1 (MEN-1) were operated on using the laparoscopic approach. Endoscopic ultrasonography was used to localize the tumor preoperatively in 90% of patients with sporadic insulinoma. In patients with MEN-1, computed tomography and octreoscan-111In demonstrated multiple tumors. Laparoscopic ultrasonography (LapUS) was performed in all patients for operative decision-making. Of 11 patients with sporadic insulinoma, laparoscopic enucleation (LapEn) was planned in 8 patients, but in 1 patient, the use of LapUS missed the tumor and the patient was converted to open surgery. Mean operating time after LapEn (seven patients) was 180 minutes, and the mean blood loss was 200 ml. The mean hospital stay was 5 days. In three of the 11 patients, laparoscopic spleen-preserving distal pancreatectomy (LapSPDP) was performed; the mean operative time was 240 minutes, and the mean blood loss was 360 ml. Postoperative complications occurred in three of seven patients after LapEn (three pancreatic fistulas managed conservatively, and one case of bleeding requiring reoperation). LapSPDP was performed in both patients with MEN-1; in one patient with splenic vessel preservation (SVP), the operating time was 210 minutes and blood loss was 650 ml, with a hospital stay of 6 days. In another patient without SVP, the operating time was 150 minutes and blood loss was 300 ml. The latter patient developed a 4-cm splenic infarct managed conservatively, and the hospital stay was 14 days. LapEn and LapSPDP are feasible and safe and achieved cure in patients with sporadic insulinoma and multiple insulinomas associated with MEN-1. However, the risk of pancreatic leakage after LapEn remains high, and LapSPDP without SVP may be associated with splenic infarct.     

Intraoperative myocardial ischemia in peripheral vascular surgery: general anesthesia vs combined sciatic and femoral nerve blocks

STUDY OBJECTIVE: The aim of this study was to compare the frequency of intraoperative myocardial ischemia in lower extremity vascular surgery with general anesthesia vs regional anesthesia via combined sciatic and femoral nerve blocks. DESIGN: This is a prospective, randomized study. SETTING: This study was set at an academic medical center. PATIENTS: The study included 50 patients scheduled for elective lower extremity vascular surgery. INTERVENTIONS: Patients in group 1 received balanced general anesthesia, whereas patients in group 2 received combined sciatic and femoral nerve blocks with 40 mL of 0.375% bupivacaine. Monitoring included a radial artery catheter and multilead, dual-channel electrocardiogram with computerized ST-segment analysis. Blood pressure and heart rate variations were maintained within 10% of preoperative values by adjusting anesthetic depth, fluid replacement, and vasoactive drug dosages. MEASUREMENTS AND MAIN RESULTS: An ST-segment depression of at least 1 mm or elevation of at least 2 mm lasting for more than 1 minute was considered a significant episode of myocardial ischemia. Intraoperative hemodynamic data and the frequency of significant ST-segment change episodes were recorded. The number of patients with ischemic episodes and the total number of these episodes were lower in group 2 than in group 1 (1 patient vs 7 patients, P = 0.02; and 2 vs 14 episodes, P = 0.04). No significant difference was found between groups 1 and 2 regarding systolic or diastolic arterial pressures, or heart rate. CONCLUSION: Compared with general anesthesia, combined sciatic and femoral nerve blocks reduce the frequency of intraoperative myocardial ischemia in patients undergoing lower extremity vascular surgery.     

Acneiform eruption secondary to cetuximab

C225 (cetuximab) is a monoclonal antibody that targets the epidermal growth factor receptor (EGF-R). It is used for the treatment of solid malignant tumors in advanced stages. It works against tumors by inhibiting cell proliferation, angiogenesis and the formation of metastases, as well as by promoting cell apoptosis. We present the case of a 64-year-old male patient affected with a colon neoplasm with hepatic metastases, for which treatment with cetuximab was indicated. He came to our department because of a skin eruption with papules and pustules located on the face, neck, presternal area and upper back, but with no cysts or comedones. The biopsy was compatible with an acneiform eruption. The patient was treated with minocycline, 100 mg/day for 2 weeks, with the clinical symptoms responding favorably. When he was given further doses of cetuximab, he once again presented with new eruptions, but of lesser intensity. Because of the high frequency with which this adverse effect appears, it is recommended that cetuximab be included on the list of drugs causing acneiform eruptions.     

Gastric cancer

Gastric cancer is one of the most common cancers and one of the most frequent causes of cancer-related deaths. The incidence, diagnostic studies, and therapeutic options have undergone important changes in the last decades, but the prognosis for gastric cancer patients remains poor, especially in more advanced stages. Surgery is the mainstay of treatment of this disease, even if it is associated with a high rate of locoregional and distant recurrence. There is ongoing debate regarding the role of adjuvant treatment In advanced disease, palliation of symptoms, rather than cure, is the primary goal of patient management. Several combination therapies have been developed and have been examined in phase III trials; however, in most cases, they have failed to demonstrate a survival advantage over the reference arm. This review summarizes the most important recommendations for the management of patients with gastric cancer.     

Dietary restraint and cognitive performance in children

Adults who attempt to restrict their dietary intake also tend to perform worse on a range of cognitive tasks. However, the extent to which this finding generalises to children has remained unclear. Following studies involving adults, we asked 44 girls (mean age = 10.1 years) to complete a simple reaction-time task and the Tower of London task. This group was selected from a local community school in the East Midlands (UK). Dietary restraint was measured using a version of the Dutch Eating Behaviour Questionnaire that had been adapted for use by children. Our results indicate that children with high restraint scores have longer reaction times and they also tend to perform worse on the TOL task. Other aspects of our data also suggest the dietary restraint may be correlated negatively with a measure of academic ability. We discuss reasons why restraint and performance might be related causally and we conclude that this issue warrants further scrutiny.