Genetic analysis of signal peptides in amphibian antimicrobial secretions.

Amphibian secretion is an important source of bioactive molecules that naturally protect the skin against noxious microorganisms. Collectively called antimicrobial peptides (AMPs), these molecules have a wide spectrum of action, targeting viruses, bacteria and fungi. Like many membrane and secreted proteins, AMPs have cleavable signal sequences that mediate and translocate the nascent polypeptide chains into the endoplasmic reticulum. Although it is accepted that the signal peptides (SPs) are simple and interchangeable, there is neither sequence nor structure that is conserved among all gene families. They derived from a common ancestor but developed different traits as they adapt to distinct environmental pressures. The aim of this study was to provide anoverview of the diversity of SPs of the frog, taking into account reported cDNA sequences and the evolutionary relationship among them. We analysed more than 2000 records that reported the relative abundance, diversity and evolutionary divergence based on the peptide signals of frog AMPs. We conclude that the physical properties of the sequence are more important than the specific peptidesin AMP SPs. Since there is significant overlapping among related genera, differences in secretion from different peptide types should be regulated by additional levels, such as posttranscriptional modifications or 5-UTR sequences.

Aerobic exercise upregulates the BDNF-Serotonin systems and improves the cognitive function in rats.

Aerobic exercise (AE) benefits brain health and behavior. Serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) are known to mediate and shape cognitive processes. Both systems share some actions: BDNF is involved in the maturation and function of 5-HT neurons. In turn, 5-HT is involved in neuroplasticity phenomena mediated by BDNF and stimulated by exercise. The aim of this work was to study the long-term effects of AE on BDNF- 5-HT systems and cognitive function in rats at different ages. A lifelong moderate-intensity aerobic training program was designed, in which aerobically exercised (E) and sedentary control (C) rats were studied at middle (8 months) and old age (18 months) by means of biochemical, immunohistochemical and behavioral assays. The levels and expression of BDNF, 5-HT, serotonin transporter (SERT) and 5-HT1A receptor were determined in selected brain areas involved in memory and learning. Immunopositive cells to neuronal nuclear protein (NeuN) in the hippocampus CA1 area were also quantified. The cognitive function was evaluated by the object recognition test (ORT). Results indicate that AE enhanced spatial and non-spatial memory systems, modulated by age. This outcome temporarily correlated with a significant upregulation of cortical, hippocampal and striatal BDNF levels in parallel with an increase in the number of hippocampal CA1-mature neurons. AE also increased brain and raphe 5-HT levels, as well as the expression of SERT and 5-HT1A receptor in the cortex and hippocampus. Old AE rats showed a highly conserved response, indicating a remarkable protective effect of exercise on both systems. In summary, lifelong AE positively affects BDNF-5-HT systems, improves cognitive function and protects the brain against the deleterious effects of sedentary life and aging.

Lifelong Aerobic Exercise Reduces the Stress Response in Rats.

The aim of this study was to analyze the effects of lifelong aerobic exercise (AE) on the adaptive response of the stress system in rats. It is well known that hypothalamic-pituitary-adrenal axis (HPA) activity differs when triggered by voluntary or forced exercise models. Male Wistar rats belonging to exercise (E) or control (C) groups were subjected to chronic AE, and two cutoff points were established at 8 (middle age) and 18 months (old age). Behavioral, biochemical and histopathological studies were performed on the main components/targets of the stress system. AE increased adrenal sensitivity (AS), brain corticosterone (CORT) and corticotropin-releasing factor (CRF), but had no effect on the thymus, adrenal glands (AGs) weight or plasma CORT. In addition, AE exerted no effect on the sympathetic tone, but significantly reduced anxiety-related behavior and emotionality. Aging decreased AS and deregulated neuroendocrine feedback, leading to an anxiogenic state which was mitigated by AE. Histopathological and morphometric analysis of AGs showed no alterations in middle-aged rats but adrenal vacuolization in approximately 20% old rats. In conclusion, lifelong AE did not produce adverse effects related to a chronic stress state. On the contrary, while AE upregulated some components of the HPA axis, it generated an adaptive response to cumulative changes, possibly through different compensatory and/or super compensatory mechanisms, modulated by age. The long-term practice of AE had a strong positive impact on stress resilience so that it could be recommended as a complementary therapy in stress and depression disease.

Developmental neurotoxic effects of graphene oxide exposure in zebrafish larvae (Danio rerio).

Although graphene oxide (GO), a nanomaterial with hexagonal planar layer, has been widely studied due to its applications in neurobiology that include drug delivery and tissue engineering, additional studies to assess its potential toxic effects are still needed. Thus, this study evaluated the effects of GO exposure (at 5, 10, 50 or 100mg/L) during six consecutive days on mortality, hatching, spontaneous movement, heart rate, morphology, locomotion behavior, acetylcholinesterase (AChE) activity, dopamine levels and relative gene expression of developmental neurology-related genes using zebrafish larvae. In the 5mg/L dose, synapsin IIa expression up-regulation was seen concomitantly with down-regulation of dat expression, showing a potential compensatory mechanism. Moreover, the 10mg/L exposure caused an increase in heart rate, in absolute turn angle, brain cell damage and a decrease in dopamine levels. These alterations may be associated with autophagosome formation found in GO-exposed larval brain. No changes were observed on higher doses of GO exposure, probably due to nanomaterial agglomeration. Taken together, these results show that toxic effects of GO exposure are not dose-dependent, and are preeminent in lower concentrations. Additional studies are needed to deepen the specific mechanisms of GO neurotoxicity and are required to elucidate its potential biomedical use.

Changes in insulin sensitivity and secretion after sleeve gastrectomy.

BACKGROUND: Sleeve gastrectomy is indicated for the treatment of obesity and related co-morbidity including diabetes. The dynamic changes in insulin secretion and sensitivity after sleeve gastrectomy are unknown. METHODS: Whole-body insulin sensitivity was measured by the euglycaemic hyperinsulinaemic clamp technique, and insulin secretion by C-peptide deconvolution after an oral glucose tolerance test (OGTT), before and 3, 6 and 12 months after sleeve gastrectomy in morbidly obese subjects. The time course of glucagon-like peptide (GLP) 1, as a marker of insulin secretion following OGTT, was also assessed. RESULTS: Ten patients were included in the study. Median (range) baseline insulin sensitivity (M-value) increased from 84.0 (20.2-131.4) mmol per kg per min at baseline to 122.8 (99.0-179.3) mmol per kg per min at 12 months after surgery (P = 0.015). Fasting insulin sensitivity, measured by homeostatic model assessment of insulin resistance, which represents a surrogate index of hepatic insulin resistance, decreased from 3.3 (1.9-5.5) to 0.7 (0.5-1.1) mg/dl · µunits/ml (P < 0.001). Total insulin secretion, measured as incremental area under the curve (AUC), after OGTT decreased from 360.4 (347.9-548.0) to 190.1 (10.1-252.0) mmol/l · 180 min at 12 months (P = 0.011). The AUC for GLP-1 increased from 258.5 (97.5-552.6) to 5531.8 (4143.0-7540.9) pmol/l · 180 min at 12 months after sleeve gastrectomy (P < 0.001). In multiple regression analysis, 51 per cent of the M-value variability was explained by GLP-1 secretion. CONCLUSION: Sleeve gastrectomy improved insulin sensitivity and reduced insulin secretion within 6 months after surgery. Although there was a correlation between insulin sensitivity and bodyweight, the major driver of the improvement in insulin sensitivity was GLP-1 secretion.

The invasion of Patagonia by Chinook salmon (Oncorhynchus tshawytscha): inferences from mitochondrial DNA patterns.

The Chinook salmon Oncorhynchus tshawytscha, which was introduced deliberately in Chile four decades ago for sport fishing and aquaculture, represents a rare example of a successful translocation of an anadromous Pacific salmon into the southern Hemisphere, offering a unique opportunity to examine the role of introduction history and genetic variability in invasion success. We used historical information and mitochondrial displacement loop sequences (D-loop) from seven colonized sites in Chile and Argentina and from native and naturalized Chinook salmon populations to determine population sources and to examine levels of genetic diversity associated with the invasion. The analysis revealed that the Chinook salmon invasion in Patagonia originated from multiple population sources from northwestern North America and New Zealand, and admixed in the invaded range generating genetically diverse populations. Genetic analyses further indicated that the colonization of new populations ahead of the invasion front appear to have occurred by noncontiguous dispersal. Dispersal patterns coincided with ocean circulation patterns dominated by the West Wind Drift and the Cape Horn Currents. We conclude that admixture following multiple introductions, as well as long-distance dispersal events may have facilitated the successful invasion and rapid dispersal of Chinook salmon into Patagonia.

Laparoscopic gastric sleeve and micronutrients supplementation: our experience.

Background. Laparoscopic gastric sleeve (LGS) has been recently introduced as a stand-alone, restrictive bariatric surgery. Theoretically, LGS attenuates micronutrients deficiencies and associated complications that were typically observed following malabsorptive procedures. The aim of this study was to assess some micronutrients and mineral deficiencies in patients undergoing LGS. Methods. In the period between July 2008 and April 2010, 138 obese patients (110 females and 28 males) with mean BMI 44.4 kg/m(2) ± 6.5, mean age 43.9 ± 10.9 years were enrolled and underwent LGS. Patients were followed up with routine laboratory tests and anthropometric measurements and assessed for nutritional status, as regards vitamin B12, folic acid, iron, hemoglobin, calcium, and vitamin D, every three months throughout 12 months. Results. 12 months after sleeve, patients did not show iron deficiency and/or anemia; plasma calcium levels were in the normal range without supplementation from the sixth month after the operation. Vitamin B12 and folic acid were adequately supplemented for all the follow-up period. Vitamin D was in suboptimal levels, despite daily multivitamin supplementation. Conclusion. In this study, we showed that LGS is an effective surgery for the management of morbid obesity. An adequate supplementation is important to avoid micronutrients deficiencies and greater weight loss does not require higher dosage of multivitamins.

Aerobic exercise prevents age-dependent cognitive decline and reduces anxiety-related behaviors in middle-aged and old rats.

Recent research involving human and animals has shown that aerobic exercise of moderate intensity produces the greatest benefit on brain health and behavior. In this study we investigated the effects on cognitive function and anxiety-related behavior in rats at different ages of aerobic exercise, performed regularly throughout life. We designed an aerobic training program with the treadmill running following the basic principles of human training, and assuming that rats have the same physiological adaptations. The intensity was gradually adjusted to the fitness level and age, and maintained at 60-70% of maximum oxygen consumption (max.VO(2)). In middle age (8 months) and old age (18 months), we studied the cognitive response with the radial maze (RM), and anxiety-related behaviors with the open field (OF) and the elevated plus maze (EPM). Aerobically trained (AT) rats had a higher cognitive performance measured in the RM, showing that exercise had a cumulative and amplifier effect on memory and learning. The analysis of age and exercise revealed that the effects of aerobic exercise were modulated by age. Middle-aged AT rats were the most successful animals; however, the old AT rats met the criteria more often than the middle-aged sedentary controls (SC), indicating that exercise could reverse the negative effects of sedentary life, partially restore the cognitive function, and protect against the deleterious effects of aging. The results in the OF and EPM showed a significant decrease in key indicators of anxiety, revealing that age affected most of the analyzed variables, and that exercise had a prominent anxiolytic effect, particularly strong in old age. In conclusion, our results indicated that regular and chronic aerobic exercise has time and dose-dependent, neuroprotective and restorative effects on physiological brain aging, and reduces anxiety-related behaviors.

First-phase insulin secretion, insulin sensitivity, ghrelin, GLP-1, and PYY changes 72 h after sleeve gastrectomy in obese diabetic patients: the gastric hypothesis.

BACKGROUND: The aim of this study was to evaluate the possible role of sleeve gastrectomy (SG) per se in the reversibility of diabetes. METHODS: Insulin secretion and peripheral insulin sensitivity using the intravenous glucose tolerance test (IVGTT) were assessed in 18 obese type 2 diabetic patients and in 10 nondiabetic obese patients before and 3 days after SG, before any food intake and any weight change occurrence. At the same time, ghrelin, GLP-1, and PYY levels were determined. RESULTS: In diabetic patients who had the disease less than 10.5 years, the first phase of insulin secretion promptly improved after SG. The early insulin area under the curve (AUC) significantly increased at the postoperative IVGTT, indicating an increased glucose-induced insulin secretion. The second phase of insulin secretion (late AUC) significantly decreased after SG in all groups, indicating an improved insulin peripheral sensitivity. In all groups, pre- and postoperatively, intravenous glucose stimulation determined a decrease in ghrelin values and an increase in GLP-1 and PYY values. However, in the group of patients with disease duration >10.5 years, the differences were not significant except for the late insulin AUC. Postoperative basal and intravenous glucose-stimulated ghrelin levels were lower than preoperative levels in all groups of patients. Basal and intravenous stimulated GLP-1 and PYY postoperative values were higher than preoperative levels in all groups. CONCLUSIONS: Restoration of the first phase of insulin secretion and improved insulin sensitivity in diabetic obese patients immediately after SG, before any food passage through the gastrointestinal tract and before any weight loss, seem to be related to ghrelin, GLP-1, and PYY hormonal changes of possible gastric origin and was neither meal- nor weight-change-related. Duration of the disease up to 10.5 years seems to be a major cut off in the pathophysiological changes induced by SG. A "gastric" hypothesis may be put forward to explain the antidiabetes effect of SG.

Laparoscopic sleeve gastrectomy as first stage or definitive intent in 300 consecutive cases.

BACKGROUND: Laparoscopic sleeve gastrectomy (SG) was originally used as a bridge to definitive surgery in high-risk patients. Recently it has been considered as a stand-alone procedure due to its effectiveness on weight loss and comorbidities resolution. This study was designed to evaluate the results of SG on complications, body mass index (BMI), and comorbidities resolution in 300 consecutive obese patients and to analyze the lesson learned from this experience. METHODS: From October 2002 to November 2009, 300 patients underwent SG. In the first 100 cases (group 1: mean BMI, 54.4±9.3), SG was intended as a first stage of biliopancreatic diversion with duodenal switch in high risk super-obese patients. In the last 200 cases (group 2: mean BMI, 45.5±7.3), SG was intended as a definitive procedure. No routine reinforcement was performed in group 1. In group 2, oversewn reinforcement was performed routinely. SG was redo surgery in 21 patients (7%). RESULTS: Mean operative time was 119±48.6 min in group 1 and 72±33.8 in group 2. Conversion rate was 0.6% (massive hepatomegaly). Mortality was 0.6%. Major postoperative complications were registered in 15 patients in group 1 and 11 in group 2. In 3 cases, a reoperation was needed. The mean BMI in group 1 was 46, 43, 39, and 31 at 6, 12, 24, and 36 months, respectively. In group 2, the mean BMI was 32.9, 30.6, and 31.7 at 6, 12, and 18 months. At 12 months, the diabetes, hypertension, and OSAS were cured on 69%, 62%, and 50% in group 1 and 88%, 57%, and 58% in group 2. In group 2, no patient required second stage. CONCLUSIONS: SG is a safe and effective treatment for morbid obesity at mid-term follow-up. SG is effective for comorbidities resolution, especially for the treatment of diabetes. Suture line reinforcement allows a significant reduction of bleeding.

[Obesity and Eating Disorders. Indications for the different levels of care. An Italian Expert Consensus Document]. / Documento di Consensus. Obesità e Disturbi dell'Alimentazione Indicazioni per i diversi livelli di trattamento.

This paper is an Italian Expert Consensus Document on multidimensional treatment of obesity and eating disorders. The Document is based on a wide survey of expert opinion. It presents, in particular, considerations regarding how clinicians go about choosing the most appropriate site of treatment for a given patient suffering from obesity and/or eating disorders: outpatient, partial hospitalization, residential rehabilitation centre, inpatient hospitalization. In a majority of instances obesity and eating disorders are long-term diseases and require a multiprofessional team-approach. In determining an initial level of care or a change to a different level of care, it is essential to consider together the overall physical condition, medical complications, disabilities, psychiatric comorbidity, psychology, behaviour, family, social resources, environment, and available services. We first created a review manuscript, a skeleton algorithm and two rating scales, based on the published guidelines and the existing research literature. As the second point we highlighted a number of clinical questions that had to be addressed in the specific context of our National Health Service and available specialized care units. Then we submitted eleven progressive revisions of the Document to the experts up to the final synthesis that was approved by the group. Of course, from point to point, some of the individual experts would differ with the consensus view. The document can be viewed as an expert consultation and the clinical judgement must always be tailored to the particular needs of each clinical situation. We will continue to revise the Document periodically based on new research information and on reassessment of expert opinion to keep it up-to-date. The Document was not financially sponsored.

Long-term effects of laparoscopic sleeve gastrectomy, gastric bypass, and adjustable gastric banding on type 2 diabetes.

BACKGROUND: This study aimed to compare the efficacy of laparoscopic sleeve gastrectomy (SG) with that of laparoscopic gastric bypass (GBP) and laparoscopic adjustable gastric banding (AGB) for glucose homeostasis in morbidly obese subjects with type 2 diabetes mellitus (T2DM) at a 3-year follow-up assessment and to elucidate the role of weight loss in the T2DM resolution after SG. METHODS: For this study, 60 morbidly obese T2DM patients (44 females and 16 males) who underwent AGB (24 patients), GBP (16 patients), or SG (20 patients) between 1996 and 2008 were retrospectively analyzed. Age, sex, body mass index (BMI), estimated weight loss (EWL), fasting glycemia, HbA1c, euglycemic hyperinsulinemic clamp, discontinuation of diabetes treatment, and time until interruption of therapy were evaluated. RESULTS: In the study, 54 patients received oral hypoglycemic agents for at least 12 months before surgery, and 6 patients received insulin. The mean follow-up period was 36 months. The resolution rate was 60.8% for the AGB patients, 81.2% for the GBP patients, and 80.9% for the SG patients. The postoperative time until interruption of therapy was 12.6 months for the AGB patients, 3.2 months for the GBP patients, and 3.3 months for the SG patients. The hyperinsulinemic euglycemic clamp test was performed 12 months after surgery for the cured patients. Insulin resistance was restored to normal values in all the patients. The greatest improvement from preoperative values occurred in the SG group. For the not-cured GBP and SG patients, an improvement of 120 mg/dl in fasting plasma glucose was observed 3 months after the surgery, suggesting an enhancement in insulin sensitivity, which determines better medical control. The resolution rate remained constant at the 36-month follow-up evaluation in both the GBP and SG groups. CONCLUSIONS: All three bariatric procedures are effective in treating diabetes, with a 3-year follow-up evaluation showing an effect that lasts. The AGB procedure was the least effective. The antidiabetic effect was similarly precocious after GBP and SG compared with AGB. This difference may indicate that a hormonal mechanism may be involved, independent of weight loss.

Long-term results of hiatal hernia mesh repair and antireflux laparoscopic surgery.

BACKGROUND: Laparoscopic antireflux surgery (LARS) represents the gold standard in the treatment of gastroesophageal reflux disease with or without hiatal hernia. It offers excellent long-term results and high patient satisfaction. Nevertheless, several studies have reported a high rate of intrathoracic wrap migration or paraesophageal hernia recurrence. To reduce the incidence of this complication, the use of prosthetic meshes has been advocated. This study retrospectively evaluated the long-term results of LARS with or without the use of a mesh in a series of patients treated from 1992 to 2007. METHODS: From November 1992 to May 2007, 297 patients underwent laparoscopic antireflux surgery in the authors' department. Crural closure was performed by means of two or three interrupted nonabsorbable sutures for 93 patients (group A), by tailored 3 x 4-cm polypropylene mesh placement for 113 patients (group B), and by nonabsorbable suture plus superimposed tailored mesh for 91 patients (group C). RESULTS: The mean follow-up period for the entire group was 95.1 +/- 38.7 months, specifically 95.2 +/- 49 months for group A, 117.6 +/- 18 months for group B, and 69.3 +/-.17.6 months for group C. Intrathoracic Nissen wrap migration or hiatal hernia recurrence occurred for nine patients (9.6%) in group A, two patients (1.8%) in group B, and only one patient (1.1%) in group C. Esophageal erosion occurred in only one case (0.49%). Functional results and the long-term quality-of-life evaluation after surgery showed a significant and durable improvement with no significant differences related to the type of hiatoplasty. CONCLUSION: Over a long-term follow-up period, the use of a prosthetic polypropylene mesh in the crura for hiatal hernia proved to be effective in reducing the rate of postoperative intrathoracic wrap migration or hernia recurrence, with a very low incidence of mesh-related complications.

Nonsurgical treatment of staple line leaks after laparoscopic sleeve gastrectomy.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is gaining popularity as a "per se" bariatric procedure due to its effectiveness on weight loss and comorbidity resolution. The most feared and life-threatening complication after LSG is the staple line leak and its management is still a debated issue. Aim of this paper is to analyze the incidence of leak and the treatment solutions adopted in a consecutive series of 200 LSG. METHODS: From October 2002 to November 2008, 200 patients underwent LSG. Nineteen patients (9.5%) had a body mass index (BMI) of >60 kg/m(2). A 48-Fr bougie is used to obtain an 80-120-ml gastric pouch. An oversewing running suture to reinforce the staple line was performed in the last 100 cases. The technique adopted to reinforce the staple line is a running suture taken through and through the complete stomach wall. RESULTS: Staple line leaks occurred in six patients (mean BMI 52.5; mean age 41.6 years). Leak presentation was early in three cases (first, second, and third postoperative (PO) day), late in the remaining three cases (11th, 22nd, and 30th PO day). The most common leak location was at the esophagogastric junction (five cases). Mortality was nihil. Nonoperative management (total parenteral nutrition, proton pump inhibitor, and antibiotics) was adopted in all cases. Percutaneous abdominal drainage was placed in five patients. In one case, a small fistula was successfully treated by endoscopic injection of fibrin glue only. Self-expandable covered stent was used in three cases. Complete healing of leaks was obtained in all patients (mean healing time 71 days). CONCLUSION: Nonoperative treatment (percutaneous drainage, endoscopy, stent) is feasible, safe, and effective for staple line leaks in patients undergoing LSG; furthermore, it may avoid more mutilating procedures such as total gastrectomy.

Two-stage laparoscopic biliopancreatic diversion with duodenal switch as treatment of high-risk super-obese patients: analysis of complications.

INTRODUCTION: The aim of this study is to retrospectively analyze the incidence of complications after two-stage laparoscopic biliopancreatic diversion with duodenal switch (Lap BPD-DS) in high-risk super-obese patients and explore the possible predictive factors of specific complications after laparoscopic sleeve gastrectomy (SG). METHODS: High-risk patients--body mass index (BMI) > 50 kg/m(2) with at least two major comorbidities: type 2 diabetes, obstructive sleep apnea syndrome (OSAS), hypertension--undergoing two-stage laparoscopic BPD-DS were retrospectively analysed. The SG pouch volume was 100-150 ml; in the second stage, the common channel and the alimentary loop were 100 cm and 150 cm, respectively. RESULTS: Eighty-seven patients (50 female, 57.5%) underwent SG (two open). The mean age was 41.8 +/- 10.22 years with BMI of 55.2 +/- 6.69 kg/m(2). Four patients had Prader-Willy syndrome. Fourteen (16.46%) patients (6 female, 42.8%) had postoperative complications such as bleeding, fistula, pulmonary embolism, transitory acute renal failure, and abdominal abscess. One patient died at postoperative day 5 of pulmonary embolism. One patient was reoperated for hemoperitoneum by laparoscopy. The risk of complications after SG was lower in patients where reinforcement of the suture line was used (0.492), while it was higher in men (1.780). Neither difference was statistically significant [p = not significant (NS)]. After 9-24 months, 27 patients (BMI 43 +/- 8 kg/m(2)) underwent a second stage of BPD-DS (two open). Major postoperative complications were registered in eight patients (29.6%): three bleeding, four duodeno-ileal stenosis and one rhabdomyolysis. Two cases of internal hernia required laparoscopic reoperation. The reoperation rate was 1/85 (1.2%) after SG and 2/27 (7.4%) after second stage. CONCLUSIONS: Complications after SG greatly decrease after the learning curve period and can be successfully managed without need of reoperation. Suture-line reinforcement, at least selectively in the middle-upper portion of the staple line and in super-super-obese patients, is recommended to decrease the incidence of specific complications.

Short-term effect of ovariectomy on osteoprogenitors in the healing rat mandibular incisor extraction socket.

UNLABELLED: OVX increased the percentage of AP-positive CFU-F in healing rat mandible. The increase of the number of osteoprogenitors was not significant in rat mandible-derived cultures but was in femur-derived ones. This suggests that the effect of OVX on osteoprogenitors is either smaller or develops later in mandible relative to femur. INTRODUCTION: Osteoprogenitors play an essential role in the regeneration process that leads to the successful integration of dental implants. However, it is unclear how systemic osteoporosis affects osteoprogenitors in oral bone. The present study was designed to determine the short-term effects of ovariectomy (OVX) on osteoprogenitors from the healing extraction socket in rat mandible. METHODS: Six-month-old rats were ovariectomized (n=8) and control rats were left intact (n=8). Two weeks post-OVX, the right mandibular incisor was extracted. Four weeks post-extraction, the basal mandibular bone between the 1st and 3rd molar in the healing extraction socket was used to determine the number of fibroblastic progenitors (CFU-F), alkaline phosphatase-positive fibroblastic progenitors (AP-positive CFU-F), Dex-dependent osteoprogenitors (CFU-O Dex) and Prog-dependent osteoprogenitors (CFU-O Prog) using colony assays (n=5). Osteocalcin mRNA expression was evaluated using in situ hybridization (n=3). Data were analyzed using two-way ANOVA or Student's t-test. RESULTS: OVX increased the percentage of AP-positive CFU-F in both mandible and femur. The number of CFU-O was increased only in femur. Osteocalcin mRNA expression in regenerating mandible was not statistically different between control and OVX animals. CONCLUSION: Our results suggest that the effect of OVX on osteoprogenitors is either smaller or develops later in mandible relative to femur.

Acute and chronic effects of Cr(VI) on Hypsiboas pulchellus embryos and tadpoles.

In the last few years there has been great concern about declines in the abundance of several species of amphibians around the world. Among amphibians, anurans have a biphasic life cycle, with aquatic tadpoles and generally terrestrial adults, and they have an extremely permeable skin, making them excellent indicators of the health of the environment. A number of different causes have been suggested for the global decline of anurans, the pollution of their habitat by chemical stressors being considered one of the major factors. Among chemical stressors, heavy metals are known for their high toxicity at very low concentrations. This study assessed short- (96 h, 'acute') and long-term (1272 h, 'chronic') exposure to Cr(VI) at lethal (3 to 90 mg 1(-1)) and sublethal concentrations (0.001 to 12 mg 1(-1)) on Hypsiboaspulchellus (previously called Hyla pulchella; see Faivovich et al. 2005) tadpoles (Fam. Hylidae) from central eastern Argentina. Fertilized eggs collected from a clean pond near La Plata (Buenos Aires Province) were used for acute and chronic toxicity testing. Assays were done under controlled laboratory conditions. Results of chronic exposure were used to assess the effect of factors such as toxicant concentration and age of organisms at the beginning of exposure on the response variables (growth, development and survival until metamorphosis). Results indicated a higher sensitivity to Cr(VI) of individuals first exposed as tadpoles than those first exposed as embryos during acute and chronic exposure. Exposure to the highest sublethal concentrations (6 to 12 mg 1(-1)) of the toxicant showed early inhibitory effects on growth of all treated organisms compensated at longer exposure periods with an increase in the growth rate compared to the control groups.

Extensive enriched environments protect old rats from the aging dependent impairment of spatial cognition, synaptic plasticity and nitric oxide production.

In aged rodents, neuronal plasticity decreases while spatial learning and working memory (WM) deficits increase. As it is well known, rats reared in enriched environments (EE) show better cognitive performances and an increased neuronal plasticity than rats reared in standard environments (SE). We hypothesized that EE could preserve the aged animals from cognitive impairment through NO dependent mechanisms of neuronal plasticity. WM performance and plasticity were measured in 27-month-old rats from EE and SE. EE animals showed a better spatial WM performance (66% increase) than SE ones. Cytosolic NOS activity was 128 and 155% higher in EE male and female rats, respectively. Mitochondrial NOS activity and expression were also significantly higher in EE male and female rats. Mitochondrial NOS protein expression was higher in brain submitochondrial membranes from EE reared rats. Complex I activity was 70-80% increased in EE as compared to SE rats. A significant increase in the area of NADPH-d reactive neurons was observed in the parietotemporal cortex and CA1 hippocampal region of EE animals.

Clinical evaluation of fibrin glue in the prevention of anastomotic leak and internal hernia after laparoscopic gastric bypass: preliminary results of a prospective, randomized multicenter trial.

BACKGROUND: Gastro-jejunal anastomotic leak and internal hernia can be life-threatening complications of laparoscopic Roux-en-Y gastric bypass (LRYGBP), ranging from 0.1-4.3% and from 0.8-4.5% respectively. The safety and efficacy of a fibrin glue (Tissucol) was assessed when placed around the anastomoses and over the mesenteric openings for prevention of anastomotic leaks and internal hernias after LRYGBP. METHODS: A prospective, randomized, multicenter, clinical trial commenced in January 2004. Patients with BMI 40-59 kg/m2, aged 21-60 years, undergoing LRYGBP, were randomized into: 1) study group (fibrin glue applied on the gastro-jejunal and jejuno-jejunal anastomoses and the mesenteric openings); 2) control group (no fibrin glue, but suture of the mesenteric openings). 322 patients, 161 for each arm, will be enrolled for an estimated period of 24 months. Sex, age, operative time, time to postoperative oral diet and hospital stay, early and late complications rates are evaluated. An interim evaluation was conducted after 15 months. RESULTS: To April 2005, 204 patients were randomized: 111 in the control group (mean age 39.0+/-11.6 years, BMI 46.4 +/- 8.2) and 93 in the fibrin glue group (mean age 42.9+/-11.7 years, BMI 46.9+/-6.4). There was no mortality or conversion in both groups; no differences in operative time and postoperative hospital stay were recorded. Time to postoperative oral diet was shorter for the fibrin glue group (P = 0.0044). Neither leaks nor internal hernias have occurred in the fibrin glue group. The incidence of leaks (2 cases, 1.8%) and the overall reoperation rate were higher in the control group (P=0.0165). CONCLUSION: The preliminary results suggest that Tissucol application has no adverse effects, is not time-consuming, and may be effective in preventing leaks and internal hernias in morbidly obese patients undergoing LRYGBP.

Prosthetic closure of the esophageal hiatus in large hiatal hernia repair and laparoscopic antireflux surgery.

BACKGROUND: Laparoscopy has become the standard surgical approach to both surgery for gastroesophageal reflux disease and large/paraesophageal hiatal hernia repair with excellent long-term results and high patient satisfaction. However, several studies have shown that laparoscopic hiatal hernia repair is associated with high recurrence rates. Therefore, some authors recommend the use of prosthetic meshes for either laparoscopic large hiatal hernia repair or laparoscopic antireflux surgery. The aim of this article was to review available studies regarding the evolution, different techniques, results, and future perspectives concerning the use of prosthetic materials for closure of the esophageal hiatus. METHODS: A search of electronic databases, including Medline and Embase, was performed to identify available articles regarding prosthetic hiatal closure for large hiatal or paraesophageal hernia repair and/or laparoscopic antireflux surgery. Techniques and results as well as recurrence rates and complications related to the use of prosthetics for hiatal closure were reviewed and compared. Additionally, recent experiences and recommendations of experienced experts in this field were collected. RESULTS: The results of 42 studies were analyzed in this review. Some techniques of mesh hiatal closure were evaluated; however, most authors prefer posterior mesh cruroplasty. The type and shape of hiatal meshes vary from small angular meshes to A-shaped, V-shaped, or complete circular meshes. The most frequently utilized materials are polypropylene, polytetrafluoroethylene, or dual meshes. All studies show a low rate of postoperative hernia recurrence, with no mortality and low morbidity. In particular, comparative studies including two prospective randomized trials comparing simple sutured hiatal closure to prosthetic hiatal closure show a significantly lower rate of postoperative hiatal hernia recurrence and/or intrathoracic wrap migration in patients who underwent prosthetic hiatal closure. CONCLUSIONS: Laparoscopic large hiatal/paraesophageal hernia repair with prosthetic meshes as well as laparoscopic antireflux surgery with prosthetic hiatal closure are safe and effective procedures to prevent hiatal hernia recurrence and/or postoperative intrathoracic wrap migration, with low complication rates. The type of mesh, particularly the size and shape, is still controversial and is a matter for future research in this field.