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Changes in intracellular [Ca2+]i levels have been shown to influence developmental processes that accompany the transition of human oligodendrocyte precursor cells (OPCs) into mature myelinating oligodendrocytes and are required for the initiation of the myelination and re-myelination processes. In the present study, we explored whether calcium signals mediated by the selective sodium calcium exchanger (NCX) family members NCX1, NCX2, and NCX3, play a role in oligodendrocyte maturation. Functional studies, as well as mRNA and protein expression analyses, revealed that NCX1 and NCX3, but not NCX2, were divergently modulated during OPC differentiation into oligodendrocyte phenotype. In fact, whereas NCX1 was downregulated, NCX3 was strongly upregulated during oligodendrocyte development. The importance of calcium signaling mediated by NCX3 during oligodendrocyte maturation was supported by several findings. Indeed, whereas knocking down the NCX3 isoform in OPCs prevented the upregulation of the myelin protein markers 2′,3′-cyclic nucleotide-3′-phosphodiesterase (CNPase) and myelin basic protein (MBP), its overexpression induced an upregulation of CNPase and MBP. Furthermore, NCX3-knockout mice showed not only a reduced size of spinal cord but also marked hypo-myelination, as revealed by decrease in MBP expression and by an accompanying increase in OPC number. Collectively, our findings indicate that calcium signaling mediated by NCX3 has a crucial role in oligodendrocyte maturation and myelin formation. [ABSTRACT FROM AUTHOR]

Bowman-Birk Inhibitor (BBI), a serine protease inhibitor derived from soybeans, has anti-inflammatory properties and is able to suppress the development of central nervous system (CNS) autoimmunity in animal models. Experimental autoimmune encephalomyelitis (EAE), a widely used animal model of multiple sclerosis (MS), is characterized by breakdown of the blood-brain barrier and infiltration of inflammatory cells into the CNS, resulting in pathology. In this study, we observed that BBI-treated mice showed delayed onset of EAE and reduced disease severity compared to control mice. BBI-treated mice had fewer inflammatory cells in the CNS including significantly reduced numbers of Th1 and Th17 cells. In the periphery, BBI treatment suppressed the development of encephalitogenic Th1 and Th17 responses early on [day 7 post-immunization (p.i.)], while after disease onset (day 14 p.i.) BBI-treated mice had stronger Th responses, as determined by antigen-specific proliferation and cytokine production. These results demonstrate that BBI treatment temporarily suppressed the development of encephalitogenic responses, but these responses eventually attained normal magnitude. Given that BBI-treated mice exhibited stronger encephalitogenic responses in the periphery during clinically manifesting EAE, delayed disease onset, and reduced numbers of CNS-infiltrating cells, it appears likely that BBI impedes the exit of pathogenic Th1 and Th17 cells from lymphoid organs, thereby delaying their migration into the CNS. [ABSTRACT FROM AUTHOR]

The purpose of this retrospective study was to analyze our results after laparoscopic repair of giant hiatal hernias with direct closure of the hiatus, since the reports document a radiological recurrence rate as high as 42%. Various studies have shown that laparoscopic hernia repair is safe and effective, and carries a lower morbidity than the open approach, but the high recurrence rates still being reported (ranging from 10 to 42%) have prompted many authors to recommend using a prosthesis. This is a report on the follow-up of 38 patients with type III and IV hiatal hernia who underwent laparoscopic repair with direct hiatal closure without the aid of meshes. From January 2000 to March 2010, 38 patients with III and IV hiatal hernia were treated at the Surgery Division of Cisanello Hospital in Pisa. Data were collected retrospectively and included demographics, preoperative symptoms, radiographic and endoscopic findings, intraoperative and postoperative complications, postoperative symptoms, barium X-ray and follow-up by medical examination and symptoms questionnaire. The sample included 12 males and 26 females, between 36 and 83 years (median age 62) with 26 type III (68.4%) and 12 type IV (31.6%) hernias. There were no conversions to laparotomy and no intraoperative or postoperative mortality. A 360° Nissen fundoplication was performed in 22 patients (57.9%) and a 270° Toupet fundoplication in 16 patients (42.1%). One patient had intraoperative complications (2.6%), and postoperative complications occurred in another three (7.9%). The follow-up was complete in all patients and ranged from 12 to 88 months (median 49 months). Barium swallow was performed in all patients and recurrence was found in five patients (13.1%); three of these patients (7.9%) were asymptomatic, while two (5.2%) were reoperated. All 38 patients' symptoms improved. Judging from our data, the recurrence rate after laparoscopic giant hiatal hernia repair with direct hiatal closure can be lowered by complying with several crucial surgical principles, e.g., complete sac excision and appropriate crural closure, adequate esophageal lengthening, and the addition of an antireflux procedure and a gastropexy. We recorded a radiological recurrence rate of 13.1% (5/38) and patient satisfaction in our series was quite high (92%). Based on these findings, the laparoscopic treatment of giant hernias with direct hiatal closure seems to be a safe and effective procedure. [ABSTRACT FROM AUTHOR]

We describe three cases of lymph proliferative diseases characterized by the presence of lymphoma cells expressing the KSHV/HHV-8 antigen with or without EBV expression. The patients were HIV seronegative without serous effusions. One case was diagnosed as KSHV-germinotropic lymphoproliferative disorder due to the presence of atypical plasmablasts involving germinal centers. These plasmablasts were positive for MUM1 and vIL6, co-expressed EBV and LNA-1 of HHV-8/KSHV, and showed a polyclonal pattern of Ig gene rearrangements on PCR. The disease was localized and the prognosis was good. In two other cases, a diagnosis of KSHV/HHV-8-related diffuse large cell B-lymphoma morphology was made. The lymphoma cells were anaplastic or frankly pleomorphic, expressed KSHV but not EBV, and were positive for CD20, MUM1, PAX-5, and vIL6. In both cases the prognosis was poor. On the basis of the features observed, we raise three considerations: (1) KSHV-related lymphoproliferative disorders represent a distinctive and heterogeneous group of diseases with variable clinico-pathologic findings and immunophenotypes (BCL6-/MUM1+/CD138- and BCL6+/MUM1+/CD138- or BCL6-/MUM1+/CD138+). (2) Although the pathogenic mechanism of HHV8 in lymphomagenesis is unclear, the presence the viral DNA in lymph nodes of HIV- patients is not a simply opportunistic infection, but is directly implicated in the pathogenesis of KSHV-related diseases; the activation of IL-6 receptor signalling may play an important role in most cases. (3) The different prognoses among different diseases with KSHV etiology may be related to the fact that the pathogenic potential appears to be constrained by a competent immune system. [ABSTRACT FROM AUTHOR]

The Na/Ca exchanger (NCX) is an important bidirectional transporter of calcium in neurons and has been shown to be involved in neuroprotection. Calcium can activate a number of cascades that can result in apoptosis and cell death, and NCX is a key factor in regulating the cytoplasmic concentration of this ion. 17-β-estradiol and insulin-like growth factor 1 (IGF-1) are known neuroprotective hormones with interacting mechanisms and effects on intracellular calcium; however, their relationship with the NCX has not been explored. In this article, the effects of these two hormones on neuronal NCX were tested using the whole-cell patch clamp technique on rat primary culture neurons. Both 17-β-estradiol and IGF-1 produced an increase in the NCX-mediated inward current and a decrease in the NCX-mediated outward current. However, the IGF-1 effect was lower than that of 17-β-estradiol, and the effect of both agents together was greater than the sum of each agent alone. Neither of the agents affected the pattern of regulation by extracellular or intrapipette calcium. Inhibitors of the IGF-1 and 17-β-estradiol receptors and inhibitors of the main signaling pathways failed to change the observed effects, indicating that these actions were not mediated by the classical receptors of these hormones. These effects on the NCX could be a mechanism explaining the neuroprotective actions of 17-β-estradiol and IGF-1, and these findings could help researchers to understand the role of the NCX in neuroprotection. [ABSTRACT FROM AUTHOR]

We report a rare complication after laparoscopic fundoplication using a dual-sided PTFE/ePTFE (Bard® Crurasoft™) mesh fixation. A 53-year-old man was re-operated for a recurrent hiatal hernia. The hiatal hernia was reinforced using a mesh. Two years later, the patient presented with serious dysphagia and weight loss. An endoscopy revealed a migrated mesh in the stomach. The mesh was excreted within the stool without notice. The PTFE/ePTFE mesh, which is designed for treating hiatal defects, is considered to have superior tissue incorporation, together with less adhesion formation and fistulation. As mesh migration into the upper gastrointestinal tract is possible, it should be used with great care in the peri-oesophageal region. [ABSTRACT FROM AUTHOR]

Rationale: Cannabis is the most commonly used illicit drug among pregnant women. Since the endocannabinoid system plays a crucial role in brain development, maternal exposure to cannabis derivatives might result in long-lasting neurobehavioral abnormalities in the exposed offspring. It is difficult to detect these effects, and their underlying neurobiological mechanisms, in clinical cohorts, because of their intrinsic methodological and interpretative issues. Objectives: The present paper reviews relevant rodent studies examining the long-term behavioral consequences of exposure to cannabinoid compounds during pregnancy and/or lactation. Results: Maternal exposure to even low doses of cannabinoid compounds results in atypical locomotor activity, cognitive impairments, altered emotional behavior, and enhanced sensitivity to drugs of abuse in the adult rodent offspring. Some of the observed behavioral abnormalities might be related to alterations in stress hormone levels induced by maternal cannabis exposure. Conclusions: There is increasing evidence from animal studies showing that cannabinoid drugs are neuroteratogens which induce enduring neurobehavioral abnormalities in the exposed offspring. Several preclinical findings reviewed in this paper are in line with clinical studies reporting hyperactivity, cognitive impairments and altered emotionality in humans exposed in utero to cannabis. Conversely, genetic, environmental and social factors could also influence the neurobiological effects of early cannabis exposure in humans. [ABSTRACT FROM AUTHOR]

Copyright of Neuroscience Bulletin is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The relative effects of clinical and psychosocial variables on outcome in celiac disease (CD) has not previously been reported. In adult patients with (CD), we studied the relationships among demographics, psychosocial factors, and disease activity with health-related quality of life (HRQOL), health care utilization, and symptoms.Methods: Among 101 adults newly referred to a tertiary care center with biopsy-proven CD we assessed: (a) demographic factors and diet status; (b) disease measures (Marsh score, tissue transglutaminase antibody (tTG) level, weight change and additional blood studies); and (c) Psychosocial status (psychological distress, life stress, abuse history, and coping). Multivariate analyses were performed to predict HRQOL, daily function, self-reported health, number of physician visits, and GI symptoms (pain and diarrhea).Results: Impaired HRQOL and daily function was associated with psychological distress and poorer coping. Self-report of poorer health was associated with poorer coping, longer symptom duration, lower education, and greater weight loss. More physician visits were associated with poorer coping, abnormal tTG levels, and milder Marsh classification. Greater pain scores were seen in those with higher psychological distress and greater weight loss. Finally, diarrhea was associated with greater psychological distress and poorer coping.Conclusions: In patients presenting to a CD referral center, psychosocial factors more strongly affect health status and GI symptoms than disease measures. [ABSTRACT FROM AUTHOR]

Copyright of Anaesthesist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Chronic inflammation is associated with cachexia and increased mortality risk in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Inflammation suppresses appetite and causes the loss of protein stores. In CKD patients, increased serum levels of pro-inflammatory cytokines may be caused by reduced renal function, volume overload, oxidative or carbonyl stress, decreased levels of antioxidants, increased susceptibility to infection in uremia, and the presence of comorbid conditions. Cachexia is brought about by the synergistic combination of a dramatic decrease in appetite and an increase in the catabolism of fat and lean body mass. Pro-inflammatory cytokines act on the central nervous system to alter appetite and energy metabolism and to provide a signal—through the nuclear factor-κB and ATP-ubiquitin-dependent proteolytic pathways—that causes muscle wasting. Further research into the molecular pathways leading to inflammation and cachexia may lead to novel therapeutic therapies for this devastating and potentially fatal complication of chronic disease. [ABSTRACT FROM AUTHOR]

Several studies have shown that laparoscopic hernia repair for large paraesophageal hiatal hernia is associated with a high recurrence rate. Therefore, some authors recommend the use of prosthetic meshes. Considering the dynamic area between the esophagus and the diaphragmatic crura with its constant motion, it is astonishing that only a minor number of surgeons describe mesh-associated complications. Between January 2000 and August 2008, 26 patients of the Centre Hospitalier Emile Mayrisch (CHEM, Luxembourg) underwent laparoscopic repair for large paraesophageal hiatal hernia (median age, 70 (range, 39–90) years). In nine patients, prosthetic mesh reinforcement was performed (7 composite/2 mono-phase mesh). Crural repair without tension was performed only with sutures. There were no conversions. Follow-up assessment was prospective with the GIQL (Gastro-Intestinal Quality of Life) Index. Responses to the GIQLI questionnaires were obtained from 20 patients (6 died of unrelated causes). Nineteen patients were satisfied with their symptom control 1 year after the operation (GIQLI 127). Sixteen patients had radiological follow-up (median, 24 months). Three patients treated without mesh (3/10) showed a radiological recurrence. All of them (3/10) had symptoms. None of the controlled patients with mesh (0/6) showed a recurrence. One patient developed a severe aortal bleeding 1, 2, and 3 weeks after the laparoscopic mono-phase mesh repair. During conventional operation, the bleeding stopped. Three years later, the follow-up showed a satisfied patient (GIQLI 127). In view of the described complication, there is still considerable controversy regarding the routine use of mesh. To increase safety, a composite mesh should be preferred. [ABSTRACT FROM AUTHOR]

Despite the high prevalence of marijuana use among pregnant women and adolescents, the impact of cannabis on the developing brain is still not well understood. However, growing evidence supports that the endocannabinoid system plays a major role in CNS patterning in structures relevant for mood, cognition, and reward, such as the mesocorticolimbic system. It is thus clear that exposure to cannabis during early ontogeny is not benign and potential compensatory mechanisms that might be expected to occur during neurodevelopment appear insufficient to eliminate vulnerability to neuropsychiatric disorders in certain individuals. Both human longitudinal cohort studies and animal models strongly emphasize the long-term influence of prenatal cannabinoid exposure on behavior and mental health. This review provides an overview of the endocannabinoid system and examines the neurobiological consequences of cannabis exposure in pregnancy and early life by addressing its impact on the development of neurotransmitters systems relevant to neuropsychiatric disorders and its association with these disorders later in life. It posits that studying in utero cannabis exposure in association with genetic mutations of neural systems that have strong relationships to endocannabinoid function, such as the dopamine, opioid, glutamate, and GABA, might help to identify individuals at risk. Such data could add to existing knowledge to guide public health platform in regard to the use of cannabis and its derivatives during pregnancy. [ABSTRACT FROM AUTHOR]

Cannabinoid receptors and their endogenous ligands have been detected from the earliest stages of embryonic development. The endocannabinoid system appears to play essential roles in these early stages for neuronal development and cell survival, although its detailed involvement in fundamental developmental processes such as proliferation, migration and differentiation has not yet been completely understood. Therefore, it is not surprising that manipulations of the endocannabinoid system by cannabinoid exposure during early developmental stages can result in long-lasting neurobehavioural consequences. The present review will summarize the possible residual behavioural effects of cannabinoid administration during pre- and perinatal as well as early postnatal development, derived from animal studies. [ABSTRACT FROM AUTHOR]

The aim of the present review is to summarize integrated neurochemical, morphological and neurobehavioral evidence, in particular from our laboratory, which emphasize the short- and long-term consequences of prenatal exposure to the cannabinoid receptor agonist WIN55,212-2 on rat glutamate transmission and cognitive functions. The results obtained provide evidence that maternal exposure to WIN55,212-2 induces an impairment of cognitive capacities in the offspring. This impairment is associated with alterations of cortical and hippocampal glutamate outflow, cortical neuron morphology and hippocampal long-term potentiation. These findings are in line with clinical data showing that the consumption of marijuana by women during pregnancy has negative consequences on the cognitive functions of their children. Thus, although it is difficult and sometimes misleading to extrapolate findings obtained from animal models to humans, the possibility that an alteration of glutamate transmission might underlie, at least in part, some of the cognitive deficits affecting the offspring of marijuana users, is supported. [ABSTRACT FROM AUTHOR]

Primary laparoscopic hiatal hernia repair is associated with up to a 42% recurrence rate. This has lead to the use of mesh for crural repair, which has resulted in an improved recurrence rate (0–24%). However, mesh complications have been observed. We compiled two cases, and our senior author contacted other experienced esophageal surgeons who provided 26 additional cases with mesh-related complications. Care was taken to retrieve technical operative details concerning mesh size and shape and implantation technique used. Twenty-six patients underwent laparoscopic and two patients open surgery for large hiatal hernia ( n = 28). Twenty-five patients had a concomitant Nissen fundoplication, two a Toupet fundoplication, and one a Watson fundoplication. Mesh types placed were polypropylene ( n = 8), polytetrafluoroethylene (PTFE) ( n = 12), biological mesh ( n = 7), and dual mesh ( n = 1). Presenting symptoms associated with mesh complications were dysphagia ( n = 22), heartburn ( n = 10), chest pain ( n = 14), fever ( n = 1), epigastric pain ( n = 2), and weight loss ( n = 4). Main reoperative findings were intraluminal mesh erosion ( n = 17), esophageal stenosis ( n = 6), and dense fibrosis ( n = 5). Six patients required esophagectomy, two patients had partial gastrectomy, and 1 patient had total gastrectomy. Five patients did not require surgery. In this group one patient had mesh removal by endoscopy. There was no immediate postoperative mortality, however one patient has severe gastroparesis and five patients are dependent on tube feeding. Two patients died 3 months postoperatively of unknown cause. There is no apparent relationship between mesh type and configuration with the complications encountered. Complications related to synthetic mesh placement at the esophageal hiatus are more common than previously reported. Multicenter prospective studies are needed to determine the best method and type of mesh for implantation. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) causes chronic hepatitis in hundreds of millions of people worldwide, which can eventually lead to hepatocellular carcinoma (HCC). The molecular mechanisms underlying HBV persistence are not well understood. TRAIL, the TNF-related apoptosis-inducing ligand, has recently been implicated in hepatocyte death during HBV infection. We report here that the HBV core protein (HBc) is a potent inhibitor of TRAIL-induced apoptosis. Overexpressing HBc significantly decreased TRAIL-induced apoptosis of human hepatoma cells, whereas knocking-down HBc expression in hepatoma cells transfected with HBV genome enhanced it. When present in the same cell, HBc blocked the pro-apoptotic effect of the HBV X protein (HBx). The resistance of HBc-expressing cells to TRAIL-induced apoptosis was associated with a significant reduction in death receptor 5 (DR5) expression. Upon transfection, HBc significantly repressed the promoter activity of the human DR5 gene. Importantly, HBc gene transfer inhibited hepatocyte death in a mouse model of HBV-induced hepatitis; and in patients with chronic hepatitis, DR5 expression in the liver was significantly reduced. These results indicate that HBc may prevent hepatocytes from TRAIL-induced apoptosis by blocking DR5 expression, which in turn contributes to the development of chronic hepatitis and HCC. They also call into question the potential side effects of HBc-based vaccines.Cell Death and Differentiation (2009) 16, 219–229; doi:10.1038/cdd.2008.144; published online 17 October 2008 [ABSTRACT FROM AUTHOR]

The use of mesh for laparoscopic repair of large hiatal hernias may reduce recurrence rates in comparison to primary suture repair. However, there is a potential risk of mesh-related oesophageal complications due to prosthesis erosion. The aim of this study was to critically evaluate a novel mesh (DualMesh) repair of hiatal hernias with particular reference to intraluminal erosion. Medical records of 19 patients who underwent laparoscopic hiatal hernia repair with DualMesh reinforcement of the crural closure were reviewed from a prospectively collected database. Quality of life and symptom analysis was performed using quality of life in reflux and dyspepsia (QOLRAD) questionnaires pre- and postoperatively after 6 weeks, 6 months, 1 year and 2 years. Barium studies were performed on patients pre-operatively and two years postoperatively to assess hernia recurrence. After 2 years, oesophagogastric endoscopy was performed to assess signs of erosion. Mean patient age was 70.5 years (range 49–85 years). Two years after hiatal hernia repair, there was significant improvement in quality-of-life scores (QOLRAD: p < 0.001). Follow-up barium studies performed at 31.3 months (range 29–40 months) after surgery showed moderate recurrent hernias (>4 cm) in 1/14 patients (7%). Endoscopies performed at 34.4 months (range 28–41 months) after surgery did not show any signs of prosthetic erosion. Laparoscopic reinforcement of primary hiatal closure with DualMesh leads to a durable repair in patients with large hiatal hernias. Long-term endoscopic follow-up did not show any signs of mesh erosion after prosthetic reinforcement of the crural repair. [ABSTRACT FROM AUTHOR]

Copyright of Wiener Klinische Wochenschrift is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The use of mesh for laparoscopic repair of large hiatal hernias may reduce recurrence rates in comparison with primary suture repair. However, there is a potential risk of mesh-related oesophageal complications due to prosthesis erosion. The aim of this study was to evaluate a lightweight polypropylene mesh (TiMesh) repair of hiatal hernias with particular reference to intraluminal erosion. Data were collected prospectively on 18 consecutive patients undergoing elective laparoscopic repair of a large hiatal hernia with the use of TiMesh between November 2004 and December 2005. Quality of life and symptom analysis was performed using QOLRAD questionnaires preoperatively and postoperatively after 6 weeks, 6 months, 1 year and 2 years. Barium studies were performed preoperatively and 2 years postoperatively to assess hernia recurrence. After 2 years, oesophagogastric endoscopy was performed to assess signs of mesh-related complications. All operations were completed laparoscopically. There was no 30-day mortality and median hospital stay was 2.8 days (range 2–13 days). Complications occurred in two patients (11%), both of whom were treated without residual disability. Two years after hiatal hernia repair, there was significant improvement in quality-of-life scores (QOLRAD 5.79, p < 0.001). There was no difference between pre- and postoperative dysphagia scores. No signs of stricture formation or prosthetic erosion were identified during endoscopic follow-up. One patient had a small (2 cm) sliding hiatal hernia demonstrated by barium studies, which was asymptomatic. Laparoscopic reinforcement of primary hiatal closure with TiMesh leads to a durable repair in patients with large hiatal hernias. Endoscopic follow-up did not show any signs of mesh-related complications after prosthetic reinforcement of the crural repair. Our preliminary results suggest that it is safe to proceed with this lightweight polypropylene mesh for reinforcement of the hiatal repair. [ABSTRACT FROM AUTHOR]

Cholelithiasis is a major source of digestive morbidity worldwide. Cholesterol stones account for the majority of gallstones in the United States and other Western countries. The pathogenesis of cholesterol gallstone disease is multifactorial with key factors including cholesterol supersaturation of bile, altered biliary motility, and nucleation and growth of cholesterol crystals. Increasing evidence suggests that many, but not all, causative factors of cholesterol gallstones are related to insulin resistance which, in association with obesity, has reached an epidemic level worldwide. Experimental studies show that hyperinsulinemia, a key feature of insulin resistance, may cause increased hepatic cholesterol secretion and cholesterol supersaturation of bile and gallbladder dysmotility, and thereby may enhance gallstone formation. Insulin resistance syndrome can be modified by environmental factors, including dietary factors. The impact of diet on insulin sensitivity is mediated by both dietary composition and its energy content. The contribution of specific dietary elements to the prevalence and incidence of cholesterol gallstone disease has been explored in animal and human studies. There is considerable evidence to suggest that different types of fatty acids, independent of the total amount of fat consumption, affect insulin sensitivity and cholesterol gallstone disease differently. The effects of salt intake, consumption of protein and carbohydrates, and alcohol drinking on insulin resistance are controversial. Additional intervention trials and controlled experimental feeding studies are needed to further clarify these relationships and to provide useful prophylactic and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Prosthetic fascial grafts are frequently used for augmentation of cruroplasty in large hiatus hernia repair to decrease the chances of recurrence. Potential complications such as intraluminal erosion may be related to the constant movement of mesh and diaphragm over the outer surface of the esophagus. This study aimed to evaluate DualMesh for repair of large hiatal defects in a porcine model. In this study, 18 Landrace × large white × Duroc crossbred pigs underwent either primary hiatal repair or tension-free prosthetic repair using DualMesh (80 × 50 mm or 80 × 100 mm). The animals were killed at 3 or 28 weeks for macroscopic and histologic evaluation of the hiatal region and gastroesophageal junction. All grafts had become encapsulated at 28 weeks, and the majority had filmy adhesions only to the visceral aspect. In all models, the esophagus moved freely over the cut edge of the prosthesis. No signs of intraluminal erosion were documented. At histologic examination, significant ingrowth was noted on the porous side of the mesh, whereas no defined mesothelial layer was identified on the capsule of the nonporous side. In this animal model of large hiatus hernia repair, DualMesh showed optimal characteristics in terms of host tissue incorporation on the porous side and absence of adhesions on the visceral side of the prosthesis. The absence of adhesions and intraluminal erosion in this study may provide reassurance to surgeons using mesh at the hiatus. [ABSTRACT FROM AUTHOR]

Although laparoscopic repair of large, mostly paraesophageal hiatal hernias is widely applied, there is a great concern regarding the higher recurrence rate associated with this procedure. In order to reduce this high recurrence rate, several techniques have been developed, mostly applying a mesh prosthesis for hiatal reinforcement. We have recently introduced a new laparoscopic technique in which the hiatal closure is reinforced with the teres ligament. To date 26 patients have been entered into this ongoing prospective study. After the operation patients were called back on a regular basis for symptom evaluation and barium swallow. All 26 patients agreed to undergo barium swallow, with a mean follow-up of 35 months. The mean operative time was 115 min. Perioperative morbidity was 11.5%, and conversion to an open procedure was performed in six cases. No mortality was registered. Anatomic recurrence, investigated by barium swallows was observed in four patients (15.3%). Of those four, only one (3.85%) had a symptomatic recurrent paraesophageal hernia; the other three had asymptomtic sliding hernias. In three of the four patients with anatomic recurrence, the diameter of the hiatal hernia was greater than 9 cm at the original operation, and the fourth patient underwent reoperation for recurrent hiatal hernia. No symptomatic recurrence was found in patients with diameter of hiatal hernia between 6 and 9 cm. Laparoscopic reinforcement of the hiatal closure with the ligamentum teres is safe and effective treatment for large hiatal hernias. However, it appears that patients with extremely large hiatal hernias are at greater risk of recurrence, and therefore large hernias are not suitable for this new technique. [ABSTRACT FROM AUTHOR]

Abstract Purpose  To evaluate absorption barrier recovery in the gastrointestinal tract after treatment with a penetration enhancer by using a poorly absorbed marker and correlate results with morphological recovery. Methods  Oral gavage of sodium dodecyl sulfate (SDS) was given to Wistar rats. Phenol red (PR) was given at different time points following administration of SDS. Blood samples were obtained from the jugular vein. Pharmacokinetic analysis was performed on the in vivo data using WinNonlin and MATLAB®5 software. The pharmacokinetic parameters of PR were compared to the negative control to measure functional recovery. The intestinal tissues were observed using light and transmission electron microscopy. Results  Absorption was highest when PR was co-administered with SDS. C max, AUC and K a decreased and T max and MAT increased as the recovery period (time between administration of SDS and PR) increased. The pharmacokinetic parameters approached the negative control profile in one hour after treatment with 1% SDS. Microscopy results showed recovery of paracellular and transcellular barrier at this time. Conclusions  Absorption barrier recovery could be measured using a poorly absorbed marker. Functional recovery showed a good correlation with morphological recovery. The local effects of SDS were found to be temporary and reversible. [ABSTRACT FROM AUTHOR]

In the present work, the forward and/or reversed Na+/Ca2+ exchange in cerebellar granular cells was suppressed by substitution of Na by Li+ before, during, and after exposure to glutamate for varied time and also using the inhibitor KB-R7943 of the reversed exchange. After glutamate challenge for 1 min, Na/Li+ substitution did not influence the recovery of low [Ca2+]i in a calcium-free medium. A 1-h incubation with 100 μM glutamate induced in the neurons a biphasic and irreve rsible [Ca2+]i rise (delayed calcium deregulation (DCD)), enhancement of [Na+]i, and decrease in the mitochondrial potential. If Na had been substituted by Li+ before the application of glutamate, i.e. the exchange reversal was suppressed during the exposure to glutamate, the number of cells with DCD was nearly fourfold lowered. However, addition of the Na+/K+-ATPase inhibitor ouabain (0.5 mM) not preventing the exchange reversal also decreased DCD in the presence of glutamate. Both exposures decreased the glutamate-caused loss of intracellular ATP. Glucose deprivation partially abolished protective effects of the Na/Li+ substitution and ouabain. KB-R7943 (10 μM) increased 7.4-fold the number of cells with the [Ca2+]i decreased to the basal level after the exposure to glutamate. Thus, reversal of the Na+/Ca2+ exchange reinforced the glutamate-caused perturbations of calcium homeostasis in the neurons and slowed the recovery of the decreased [Ca2+]i in the post-glutamate period. However, for development of DCD, in addition to the exchange reversal, other factors are required, in particular a decrease in the intracellular concentration of ATP. [ABSTRACT FROM AUTHOR]

The present document contains recommendations for assessment, prevention and treatment of cardiovascular risk for HIV-infected patients. All recommendations were graded according to the strength and quality of the evidence and were voted on by 73 members of the Italian Cardiovascular Risk Guidelines Working Group which includes both experts in HIV/AIDS care and in cardiovascular and metabolic medicine. Since antiretroviral drug exposure represents only one risk factor, continued emphasis on an integrated management is given. This should include prevention and treatment of known cardiovascular risk factors (such as dyslipidaemia, diabetes, insulin resistance, healthy diet, physical activity, avoidance of smoking), but also rational switch of antiretroviral drugs. A rational switch strategy should consider both metabolic and anthropometric disturbances and effectiveness of antiretroviral regimens. [ABSTRACT FROM AUTHOR]

Control of intracellular calcium signaling is essential for neuronal development and function. Maintenance of Ca2+ homeostasis depends on the functioning of specific transport systems that remove calcium from the cytosol. Na+/Ca2+ exchange is the main calcium export mechanism across the plasma membrane that restores resting levels of calcium in neurons after stimulation. Two families of Na+/Ca2+ exchangers exist, one of which requires the co-transport of K+ and Ca2+ in exchange for Na+ ions. The malfunctioning of Na+/Ca2+ exchangers has been related to the development of pathological conditions in the regulation of neuronal death after hypoxia–anoxia, brain trauma, and nerve injury. In addition, the Na+/Ca2+ exchanger function has been associated with impaired Ca2+ homeostasis during aging of the brain, as well as with a role in Alzheimer’s disease by regulating β-amyloid toxicity. In this review, we summarize the current knowledge about the Na+/Ca2+ exchanger families and their implications in neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Background: Biologic prosthetics may circumvent mesh-related complications at the esophageal hiatus by becoming remodeled by native cells. We present our experience with acellular human dermal matrix in the repair of difficult hiatal hernias (HH).Methods: Records of 17 patients who underwent laparoscopic HH repair using acellular human dermis to buttress the crural closure were analyzed. Hernias were paraesophageal (PEH) in 12 patients, large type 1 in 1 patient, and recurrent after prior HH repair in 4 patients. Barium swallow (BAS) was obtained 6-12 months after surgery. (Data are presented as mean +/- standard deviation.)Results: Mean patient age was 65 +/- 12 years and BMI was 31 +/- 4. Mean gastroesophageal (GE) junction distance above the diaphragm in the PEHs was 4.9 +/- 1.5 cm; 9 of 12 patients with PEH had more than 50% of the stomach in the chest. Mean operating time was 273 +/- 48 min. Average hiatal defect size was 4.7 x 2.7 cm, with 4.2 +/- 1.2 sutures used to close the crura. Nissen fundoplication was performed in all patients, esophageal lengthening in four patients, and anterior gastropexy in three patients. Mean hospital length of stay (LOS) was 2.3 +/- 0.8 days. Mean followup was 14.4 +/- 4.4 months. Postoperatively, only one (6%) patient had heartburn/regurgitation, one (6%) had mild dysphagia, and two (12%) take proton pump inhibitors. Followup BAS at 10.3 +/- 4.9 months after surgery showed small recurrent hernias in two patients (12%), but only one was symptomatic. In addition, there was one symptomatic failure of a redo Nissen in an obese patient. Reoperative gastric bypass 15 months later showed an intact crural closure with a remodeled buttress site.Conclusions: Acellular human dermal matrix may be an effective method to buttress the crural closure in patients with large hiatal hernias. Longer followup in larger numbers of patients is needed to assess the validity of this approach. [ABSTRACT FROM AUTHOR]

Hiatus hernia (HH) is a condition characterized by herniation of the intra-abdominal organs into the thorax. Of the several types that have been identified, the most common is type I (sliding) HH. Congenital predisposition and acquired factors, for example trauma and iatrogeny, have been identified as causative factors. There is a strong association between gastroesophageal reflux disease and HH-the prevalence of reflux in HH may reach 94%. Many methods have been used to treat reflux disease and HH, among which are laparoscopic techniques, which gained popularity as a safe method of treatment. Primary crural repair without mesh application was found to have a recurrence rate of up to 42%. This led to the introduction of mesh in HH repair, which was associated with a significant decrease in recurrence rate. Collagen and its relation to hernia have been investigated for several decades. Collagen has mechanical properties sufficient to enable it to support healed scars and other tissues. Nineteen distinct types of collagen have been recognized, the most common of which are types I and III. Type III collagen is the major constituent of early granulation tissue whereas type I predominates as healing proceeds. Collagen fibers are imbedded in extracellular matrix (ECM), which is in continuous process of synthesis and degradation under the action of matrix metalloproteinases. Many authors have studied the role of collagen in ventral hernia and have even defined hernia as a disease of the ECM. The relationship between collagen and HH, and its recurrence, is not fully understood and needs further investigation. [ABSTRACT FROM AUTHOR]

The aims of the present study were to compare effects of sodium alginate and the antacid magaldrate anhydrous in adults with gastroesophageal reflux (GOR) symptoms. Patients with heartburn and/or acid regurgitation for at least 3 days in the week before the study started (n=203) were randomized to receive a single dose of sodium alginate or magaldrate anhydrous at the onset of symptoms during a 3-day run-in period. Patients with symptoms during the run-in (n=191) were rerandomized to receive a 14-day treatment with either drug given as four daily doses. A speed of action < or =30 min was significantly more frequent among patients in the alginate group (49.4% vs. 40.4%; P=0.0074). A trend toward a more prolonged duration of action (median: 16.5 vs. 12.7 hr) and a greater sum of the symptom intensity difference (median: 40.0 vs. 31.0) was observed in the sodium alginate group. Total disappearance of symptoms was reported in 81.6% and 73.9% of patients in the sodium alginate group and magaldrate group, respectively. We conclude that sodium alginate was faster than magaldrate in relieving GRO symptoms and showed a tendency toward a more prolonged duration of action and a higher level of efficacy. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is a multisystem disease of unknown etiology. It is characterized by excessive cutaneous and visceral fibrosis, damage to small blood vessels, and production of autoantibodies. Interleukin-13 (IL-13) has been shown to be involved in abnormal fibrosis in other diseases. Therefore, we have evaluated its possible involvement in SSc. We analyzed four IL13 gene polymorphisms, rs1800925 (IL13-1055), rs20541 (Arg130Gln), rs847, and rs2243204 in 107 unrelated SSc patients (40 patients having diffuse cutaneous form and 67 patients having limited cutaneous form) and in 170 controls. All subjects were Caucasians. In the total patient population and in the diffuse cutaneous subset, we observed an association between two IL13 polymorphisms, IL13 rs1800925 (IL13-1055), and IL13 rs2243204, and disease ( p=0.03–0.04). The IL13 rs2243204T allele was more common in SSc patients ( p=0.01, OR=2.3 CI 1.21–4.38) and in the diffuse cutaneous form ( p=0.01, OR=2.95, CI 1.35–6.49) than in control subjects. Our result supports the suggestion that polymorphisms in IL13 are associated to SSc and skin fibrosis process. However, further studies on larger and independent population and functional analyses are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Signs of an activated immune system can be observed already in the early stages of chronic kidney disease (CKD). Markers of a chronically activated immune system are closely linked to several complications of CKD, such as accelerated atherosclerosis, vascular calcification, insulin resistance, increased muscle catabolism, loss of appetite, bone remodeling, and increased peritoneal permeability. Interestingly, all the aforementioned pathological states resemble a state of accelerated ageing and are strongly associated with increased morbidity and mortality in CKD patients. In recent studies, signs of inflammation have been shown as predictors for mortality in dialysis patients, and the role of inflammation as a risk factor for complications of CKD in children has emerged. Although preliminary findings suggest that inflammation is highly prevalent in the pediatric population with CKD, information related pathogenic links and to clinical outcomes is lacking. For the future, it is crucial for investigations to address the mechanisms and complications of inflammation that are manifested in pediatric patients with CKD in all stages. Since early identification and intervention may generate the most efficient strategies for prevention and treatment of cardiovascular disease in CKD patients, the pediatric population deserves special attention in future studies. In this review, we discuss the mechanisms involved in the inflammatory activation and the main causes and consequences of the inflammatory state observed in the CKD patient, with special emphasis on the pediatric population. [ABSTRACT FROM AUTHOR]

Triple therapy including clarithromycin, amoxicillin, and a proton pump inhibitor (PPI) has been recommended as the treatment of choice for Helicobacter pylori eradication. This regimen is now challenged by an increasing level of clarithromycin resistance that jeopardizes the treatment success. When clarithromycin resistance has been detected, or when its rate is known to be high in the geographic area, this drug cannot be used. It can be replaced by metronidazole, the resistance of which has a limited clinical relevance. Another option is to prescribe tetracycline and metronidazole with a PPI or ranitidine bismuth citrate. New antibiotics such as levofloxacin or rifabutin can also be used in combination with amoxicillin and a PPI. Probiotics can be added to all of these regimens to improve compliance by decreasing adverse events. But some authors advocate a quadruple therapy as a first-line treatment. Solutions to improve the limitations of this last regimen are now being proposed. Clarification of the controversial treatment indications such as gastroesophageal reflux disease or prevention of nonsteroidal anti-inflammatory drug gastroduodenal symptoms has been made. The question of prevention of gastric carcinoma by H. pylori eradication remains unanswered. [ABSTRACT FROM AUTHOR]

The reproducibility of rectal visceral sensitivity using the barostat double-random staircase method was evaluated. We tested 15 healthy women and 18 women with irritable bowel syndrome twice. Pressure, volume, and tension were measured at first sensation of gas, stool, and discomfort. There was no significant difference between test and retest. Three different indexes were used as measures of reproducibility. The intraclas correlation coefficients, considered to demonstrate acceptable reproducibility when higher than 0.80, ranged from 0.76 to 0.93 in the healthy volunteers and from 0.53 to 0.88 in the patients. The pooled coefficients of variation ranged from 10 to 24% in the healthy volunteers and from 11 to 49% in the patients. The repeatability coefficients are also given. The results indicate that barostat visceral sensitivity measurements in the rectum may be applicable when comparing groups of subjects. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the relationship between interleukin 6 (IL-6), transforming growth factor (TGF)-beta 1, IL-6 soluble receptors, and biochemical parameters of bone turnover after kidney transplantation. Of 64 patients enrolled in the study, 19 received the kidney transplant 2 to 12 months before the study, and 45 within the previous 15 to 175 months. We measured IL-6, TGF-beta 1, intact parathyroid hormone (PTH) bone alkaline phosphatase (BALP), osteocalcin (OC), and procollagen type I propeptide (P1CP) concentrations in the serum, and deoxypyridinoline crosslinks (DPD) in the urine of the patients. In 16 patients in the first posttransplantation year, the concentrations of IL-6 (P = 0.02), TGF-beta 1 (P = 0.01), BALP (P = 0.0002), OC (P = 0.001), and DPD (P = 0.01) were significantly higher than in patients with longer posttranslation period. Statistically significant negative correlation was found between posttransplantation time and IL-6 (P = 0.04), BALP (P = 0.003), OC (P = 0.0009), P1CP (P = 0.03), and DPD (P = 0.01) concentrations. Repeated measurements of the investigated parameters in the first posttransplantation year showed a significant decrease only in TGF-beta 1 level. In all patients, IL-6 correlated positively with PTH (P = 0.0009) and DPD (P = 0.03), and IL-6 soluble receptor (IL-6 sR) with DPD (P = 0.03). A decrease in IL-6 and TGF-beta 1 concentrations that paralleled the decrease in bone turnover markers in the posttransplantation period indicated that IL-6 and TGF-beta 1 were probably involved in the bone turnover after kidney transplantation. [ABSTRACT FROM AUTHOR]

Background Bile salts (BSs) stimulate cholangiocyte proliferation in vitro and in vivo in normal rats. In this study, we evaluated the effects of BS-enriched diets on cholangiocyte proliferative activity already triggered by partial bile-duct ligation (pBDL), a surgical model that induces mild cholestatic conditions, focusing our attention on ursodeoxycholate (UDC). Methods Animals ( n=45) were fed either a standard diet, or a 0.2% deoxycholate- or 0.2% UDC-enriched diet for 4 weeks. Then, in each group, ten animals underwent pBDL and five underwent sham operation. Serum and biliary BS levels, serum cholestasis and cytolysis indexes, as well as liver conventional histology, apoptosis and proliferative activity were evaluated 48 h after the operation. Results Animals that underwent pBDL showed sustained proliferative response compared with sham-operated rats. BS-enriched diets did not influence cholangiocyte proliferation in sham-operated rats. However, significantly increased proliferation was observed in pBDL rats fed a UDC-enriched diet. The evaluation of humoral and histological parameters excluded the possibility that the increased proliferation induced by UDC-enriched diet could be related to concomitant liver cell damage. Conclusion A UDC-enriched diet is able to amplify the magnitude of the cholangiocyte hyperplastic process, which occurs by a stimulatory mechanism after partial bile-duct ligation. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (HP) has been proposed as a mechanism of functional dyspepsia, but its role is still unclear. Our aim was to investigate the association between HP infection and dyspeptic symptoms and to verify whether the infection affects the pathophysiological mechanism of functional dyspepsia. The presence of HP and its association with dyspeptic symptoms were studied in 326 patients. Also, the effect of HP infection on solid/liquid gastric emptying rates, gastric sensitivity, and accommodation to meal was studied. HP was present in 17% of the patients, who showed symptom prevalence similar to that of HP-negative patients. Presence of HP did not significantly affect gastric emptying rates for solids and liquids, discomfort sensitivity thresholds (8.7 ± 0.3 vs 9.8 ± 0.9 mm Hg), or mealinduced gastric relaxation (133 ± 12 vs 125 ± 29 ml; all P's NS). In conclusion, in patients with functional dyspepsia the presence of HP infection does not seem to affect significantly the overall prevalence of symptoms or the gastric sensory-motor functions. [ABSTRACT FROM AUTHOR]

Behavioral and neurochemical effects of perinatal alcohol exposure (3% v/v solution from Day 15 of gestation to Day 7 after parturition) have been investigated in Sardinian alcohol-preferring (sP) and alcohol-nonpreferring (sNP) rat lines, selectively bred for opposite alcohol preference and consumption. In an elevated zero-maze model of anxiety, sucrose-exposed sP rats (sP-S): (i) spent significantly less time on the open arms (TO); (ii) exhibited a significantly lower number of head dips (HDIPS); and (iii) showed a higher number of stretched attend-postures (SAP) than sucrose-exposed sNP rats (sNP-S) at 90 and 180 days of age. The two rat lines displayed different emotional reactivity in response to alcohol exposure. Subtle differences in sexual behavior and ultrasonic emission (latency to the first intromission and to the first 50 kHz call) were observed between sP-S and sNP-S rats. sP-alcohol exposed (sP-A) offspring exhibited a higher latency to the first intromission than sNP-alcohol (sNP-A) treated rats. Moreover, a lower number of sP-A rats exhibited both intromission and ejaculation with respect to sNP-A animals. sP-S rats were significantly slower in recover of the righting reflex than sNP-S animals after a challenge dose of alcohol (3 g/kg, i.p.). Perinatal alcohol did not affect either onset or duration of sleep time in either line. Neurochemical experiments have shown that perinatal alcohol did not influence basal dopamine levels or amphetamine-induced dopamine increase in the prefrontal cortex of either sP or sNP offspring. These results, showing an endpoint-specific differential sensitivity of sP and sNP lines to perinatal low alcohol exposure, indicate that genetic factors could be responsible for selective susceptibility to behavioral alterations induced by developmental treatment with this drug of abuse. [Copyright &y& Elsevier]

Oral sumatriptan in 100-mg tablets is an effective and well tolerated treatment for the acute migraine attack. Since the launch of that dose, further studies have suggested good efficacy also for lower doses. This Italian multicentre study aimed at evaluating patient preference between the 50- and 100-mg does for acute treatment of migraine. Data on efficacy and safety are provided as secondary end points of this trial. The study design is on open basis: the patients treated their first 3 migraine attacks with 50 mg sumatriptan and then were able to choose whether to increase the dose to 100 mg or to continue with the initial treatment for the next 3 attacks. Two hundred one patients treated at least 3 attacks and 182 treated 6 attacks: 68% of the patients, after the third attack, preferred to continue with 50-mg sumatriptan tablets, while 32% preferred to switch to the 100-mg dose. In the first 3 attacks treated with 50 mg, 60% of patients improved at 2 hours and 72% at 4 hours after the first dose. In the set of patients that preferred to use 100 mg for the second block of 3 attacks (32%), the improvement at 2 and 4 hours after the dose was respectively 34% and 48%. Minor adverse events were reported by 15% of the patients. We conclude that less than one-third of patients treated with sumatriptan needs the 100-mg dose. [ABSTRACT FROM AUTHOR]

The article presents a list of consultants to whom the editor is acknowledging for their contribution to the periodical including H. Abcarian, M. Albert and B. Annibale.

This study allowed evaluation and comparison of the precision (20 samples) and agreement (200 samples) of the relative and absolute values of the monocyte count using three methods: microscopic, flow cytometry and the automated ABX Vega hematology analyzer. Flow cytometry is the most precise method, even if the coefficient of variation of the automated analyzer is very similar. The coefficient of correlation between the ABX Vega and the flow cytometer is very satisfactory (r = 0.8042). This study of the agreement also made it possible to confirm the difficulty that automated hematology analyzers have in differentiating between some granulocytes and monocytes and their propensity to overstimate the latter when the sample includes immature forms of granulocytes. This fact stresses the importance of the microscopic method, despite its lack of precision. The observed discrepancies did not lead to any difficulties in clinical interpretation; however, this finding should be taken into consideration, particularly in myleoproliferative syndromes and the laboratory monitoring of chemotherapy. [ABSTRACT FROM AUTHOR]

Long-term O prescription in chronic non-COPD hypoxic lung disease is, at present, based largely on physiological rather than on clinical studies. Controlled long-term studies in this field are difficult to perform. The cooperation of many centers is necessary to obtain a large and homogeneous population as the incidence of these diseases is significantly lower than COPD. [ABSTRACT FROM AUTHOR]

Antigens, antibodies and immune complexes seem to play a major role in the course of malignant melanoma, in detection of the disease progression, in treatment planning and monitoring. Of particular interest are cell and matrix adhesion molecules, growth factors and cytokines, proteases, gan-gliosides and major histocompatibility complex class I and II molecules. Antigens expressed on melanoma cells, but not on mature melanocytes, may be used as markers for the degree of the differentiation of the melanoma cells. The more the melanoma cells are dedifferentiated, the smaller is the antigenic similarity to normal melanocytes. Also, different antigens may be identified in various stages of the disease and may be used as tumor markers for disease recurrence or progression. Certain melanoma-associated antigens (MAA) such as epidermal growth factor receptor and adhesium molecules can be modulated by cytokines. Early melanoma evokes an antigen-derived T cell response, which becomes attenuated with the progression of the disease. A variety of cell adhesion molecules present on melanoma cell surfaces may play a role in regulation of cellular cytotox-icity. Free antimelanoma antibodies are usually not detectable in the sera of patients with melanoma, possibly due to their binding to shed antigens and formation of immune complexes or to tissue antigens. When bound to normal melanocytes, they cause the appearance of associated hypopigmentation. The identification of melanoma surface antigens led to generation of monoclonal antimelanoma antibodies (MAb) by laboratories. Strategies utilizing MAb based on immunologic approaches have been developed. MAb to tumor-associated antigens of melanoma cells may be used for therapeutic purposes in man. Sera of patients with vitiligo were capable of causing regression of melanoma metastases in mice due to the presence of a high titer of naturally occurring antimelanoma antibodies. Immunization of melanoma patients with vaccines containing treated melanoma cells or specific melanoma antigens or anti-idiotypic antibodies resulted in an increasing titer of antimelanoma antibodies and regression of the tumor to some extent. The appearance of hypopigmentation in patients with melanoma serves as proof for the activity of antimelanoma antibodies, although its association with the prognosis is still not clear. The thorough investigation in the field of MAA and related antibodies is aimed at improving specific antimelanoma immunotherapy, such as antigenic targeting or enhancement of production of autoantibodies, as well as better understanding of the process of metastasis and the melanoma-immune system interaction. Copyright © 1994 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Two immunotoxins were prepared using monoclonal antibodies (mAb) directed towards two distinct epitopes of the gp185 extracellular domain, and the type I ribosome inactivating protein (RIP) plant toxin saporin 6. Cell protein synthesis inhibition assay reveals that the immunotoxins display a potent and specific cytotoxicity that is characterized by a slow rate, since the time required to inhibit incorporation of radiolabeled leucine completely ranges from 36 h to 60 h depending on the target cell line and the immunotoxin. Because this feature may hamper the immunotherapeutic use of these conjugates we analysed this further by studying the early phases of internalization of immunotoxins by immunoelectron microscopy. The results of this study have demonstrated that the distribution pattern of the immunotoxins and of the unconjugated mAb over the cell surface overlaps. Similarly the mAb and immunotoxins are internalized into the cell by two different pathways: via clathrin-coated pits or via smaller uncoated pits and vesicles. A higher degree of internalization is achieved when the two immunotoxins are used in combination. Unlike the slow kinetics of cell intoxication the process of immunotoxin endocytosis is characterized by a rapid rate of internalization (above 40% at 5 min in the SK-BR-3 cell line). Although these findings provide no clue to explain the mechanisms of the slow rate of cytotoxicity of the two immunotoxins their rapid internalization indicates that these reagents can be exploited in immunotherapeutic approches to gp185-expressing malignancies. [ABSTRACT FROM AUTHOR]

A number of oocyte characteristics have been associated with fertilization, implantation and live-birth rates, albeit without reaching a consensus. This study aims to delineate possible associations between oocyte characteristics, oocyte behavior during intracytoplasmic sperm injection (ICSI), fertilization potential, and laboratory outcomes. Four-hundred and seventy-seven patients, yielding 3452 oocytes, were enrolled in this prospective observational study from 2015 to 2018. Οoplasm granularity was associated with poor embryo quality and higher probabilities of post-ICSI oocytes and embryos discarded in any developmental stage and never selected for embryo transfer or cryopreservation (p < 0.001). Both sudden or difficult ooplasm aspiration, and high or lack of resistance during ICSI were associated with either a poor Zygote-Score or fertilization failure (p < 0.001). Sudden or difficult ooplasm aspiration and high resistance during ICSI penetration were positively associated with resulting to a post-ICSI oocyte or embryo that would be selected for discard. Evaluation of oocyte characteristics and oocyte behavior during ICSI may provide early information regarding laboratory and cycle outcomes. Particularly, ooplasm granularity, and fragmentation of polar body, along with sudden or difficult ooplasm aspiration and high or lack of resistance during ICSI penetration may hinder the outcome of an ICSI cycle. The associations presented herein may contribute towards development of a grading system or a prediction model. Taking into account information on oocytes and ICSI behavior may effectively assist in enhancing IVF outcome rates. [ABSTRACT FROM AUTHOR]