Tetrabromobisphenol A acts a neurodevelopmental disruptor in early larval stages of Mytilus galloprovincialis.

Tetrabromobisphenol A-TBBPA, a widely used brominated flame retardant detected in aquatic environments, is considered a potential endocrine disruptor-ED for its reproductive/developmental effects in vertebrates. In aquatic invertebrates, the modes of action of most EDs are largely unknown, due to partial knowledge of the mechanisms controlling neuroendocrine functions. In the marine bivalve Mytilus galloprovincialis, TBBPA has been previously shown to affect larval development in the 48 h larval toxicity assay at environmental concentrations. In this work, the effects of TBBPA were further investigated at different times post-fertilization. TBBPA, from 1 µg/L, affected shell biogenesis at 48 hours post fertilization-hpf, as shown by phenotypic and SEM analysis. The mechanisms of action of TBBPA were investigated at concentrations of the same order of magnitude as those found in highly polluted coastal areas (10 µg/L). At 28-32 hpf, TBBPA significantly affected deposition of both the organic matrix and CaCO3 in the shell. TBBPA also altered expression of shell-related genes from 24 to 48 hpf, in particular of tyrosinase, a key enzyme in shell matrix remodeling. At earlier stages (24 hpf), TBBPA affected the development of dopaminergic, serotoninergic and GABAergic systems, as shown by in situ hybridization-ISH and immunocytochemistry. These data contribute draw adverse outcome pathways-AOPs, where TBBPA affects the synthesis of neutrotransmitters involved in key events (neurodevelopment and shell biogenesis), resulting in phenotypic changes on individuals (delayed or arrested development) that might lead to detrimental consequences on populations.

Bisphenol A interferes with first shell formation and development of the serotoninergic system in early larval stages of Mytilus galloprovincialis.

Bisphenol A-BPA, a widespread plastic additive, is an emerging contaminant of high concern and a potential endocrine disruptor in mammals. BPA also represents a potential threat for aquatic species, especially for larval stages. In the marine bivalve Mytilus galloprovincialis, BPA has been previously shown to affect early larval development and gene transcription. In this work, the effects of BPA (0.05-0.5-5 µM) were further investigated at different times post fertilization (24-28-32-48 hpf). BPA induced concentration-dependent alterations in deposition of the organic matrix and calcified shell at different larval stages, as shown by double calcofluor/calcein staining, resulting in altered phenotypes at 48hpf. Transcription of Tyrosinase-TYR, that plays a key role in remodelling of the shell organic matrix, and of HOX1, a member of homeobox genes involved in larval shell formation and neurogenesis, were evaluated by In Situ Hybrydization-ISH. BPA altered the spatial pattern of expression of both genes, with distinct effects depending on the concentration and developmental stage. Moreover, BPA affected the time course of mRNA levels for TYR from 24 to 48hpf. BPA impaired development of serotonin-5-HT-immunoreactive neurons at different times pf; at 48hpf, the reduction in the number of serotoninergic neurons was associated with developmental delay and downregulation of the 5-HT receptor-5-HTR. All the effects were observed from the lowest concentration tested, corresponding to detectable BPA levels in contaminated coastal waters. These data demonstrate that BPA interferes with key processes occurring during the first developmental stages of mussels, thus representing a potential threat for natural populations.

Insight into the microbial communities associated with first larval stages of Mytilus galloprovincialis: Possible interference by estrogenic compounds.

The microbiota, the host-associated community of microbes, play important roles in health status and whole body homeostasis of all organisms, including marine species. In bivalves, the microbiota composition has been mainly investigated in adults, whereas little information is available during development. In this work, the microbiota composition of the first larval stages of Mytilus galloprovincialis was evaluated by 16S rRNA gene-based profiling, at 24 and 48 hours post fertilization in comparison with those of eggs and sperm. The main genera detected in both larvae (Vibrio, Pseudoalteromonas, Psychrobium, Colwellia) derived from eggs. However, a clear shift in microbiota was observed in developing larvae compared to eggs, both in terms of core microbiome and relative abundance of different genera. The results provide a first insight into the composition of the microbial communities associated with gametes and early larvae of mussels. Moreover, the impact on larval microbiome of estrogenic chemicals that potentially affect Mytilus early development, 17ßestradiol-E2, Bisphenol A-BPA and Bisphenol F-BPF (10 µg/L), was investigated. Exposure to estrogenic chemicals leads to changes in abundance of different genera, with distinct and common effects depending on the compound and larval stage. Both potential pathogens (Vibrio, Arcobacter, Tenacibaculum) and genera involved in xenobiotic biotransformation (Oleispira, Shewanella) were affected. The effects of estrogenic compounds on larval microbiome were not related to their developmental effects: however, the results address the importance of evaluating the impact of emerging contaminants on the microbiota of marine invertebrates, including larval stages, that are most sensitive to environmental perturbations.

Characterization of the main steps in first shell formation in Mytilus galloprovincialis: possible role of tyrosinase.

Bivalve biomineralization is a highly complex and organized process, involving several molecular components identified in adults and larval stages. However, information is still scarce on the ontogeny of the organic matrix before calcification occurs. In this work, first shell formation was investigated in the mussel Mytilus galloprovincialis. The time course of organic matrix and CaCO3 deposition were followed at close times post fertilization (24, 26, 29, 32, 48 h) by calcofluor and calcein staining, respectively. Both components showed an exponential trend in growth, with a delay between organic matrix and CaCO3 deposition. mRNA levels of genes involved in matrix deposition (chitin synthase; tyrosinase- TYR) and calcification (carbonic anhydrase; extrapallial protein) were quantified by qPCR at 24 and 48 hours post fertilization (hpf) with respect to eggs. All transcripts were upregulated across early development, with TYR showing highest mRNA levels from 24 hpf. TYR transcripts were closely associated with matrix deposition as shown by in situ hybridization. The involvement of tyrosinase activity was supported by data obtained with the enzyme inhibitor N-phenylthiourea. Our results underline the pivotal role of shell matrix in driving first CaCO3 deposition and the importance of tyrosinase in the formation of the first shell in M. galloprovincialis.

In vivo immunomodulatory and antioxidant properties of nanoceria (nCeO2) in the marine mussel Mytilus galloprovincialis.

Cerium nanoparticles (nCeO2) are increasingly utilized in a wide variety of industrial, environmental and biomedical applications, and are therefore expected to be released in the aquatic environment. Due to its peculiar redox properties, nCeO2 may present unique hazards to environmental and human health. Previous data showed that in the hemocytes of the marine bivalve Mytilus galloprovincialis, in vitro exposure to a particular type of nCeO2 (9 nm, characterized by negative ζ-potential, high H2O2 scavenging capacity and Ce3+/Ce4+ surface ratio) reduced basal ROS production, lysosomal membrane stability and phagocytic activity in the presence of hemolymph serum; the effects observed were partly ascribed to the formation of a SOD-protein corona in the hemolymph. In this work, the in vivo effects of this type of nCeO2 were investigated in mussels exposed to 100 µg/L nCeO2 for 96 h; several lysosomal, immune, inflammatory and antioxidant biomarkers were measured at cellular (hemocytes) and tissue (gills, digestive gland) level. Molecular responses were evaluated in hemocytes and digestive gland by determining expression of 11 selected genes related to known biological functions. The results show specific immunomodulatory and antioxidant effects of nCeO2 at different levels of biological organization in the absence of Cerium tissue accumulation. These data further support the redox mechanisms at the basis of the physiological effects of nCeO2. Finally, in order to evaluate the possible impact at the whole organism level, the effects of nCeO2 were evaluated in the 48 h embryotoxicity assay in a wide concentration range. However, nCeO2 exposure resulted in a small reduction in normal embryo development. Overall, the results demonstrate that in mussels nCeO2 can selectively modulate different physiological processes at different levels of biological organization.

Effects of nanosilver on Mytilus galloprovincialis hemocytes and early embryo development.

Silver nanoparticles (AgNP), one of the main nanomaterials for production and use, are expected to reach the aquatic environment, representing a potential threat to aquatic organisms. In this study, the effects of bare AgNPs (47 nm) on the marine mussel Mytilus galloprovincialis were evaluated at the cellular and whole organism level utilizing both immune cells (hemocytes) and developing embryos. The effects were compared with those of ionic Ag+(AgNO3). In vitro short-term exposure (30 min) of hemocytes to AgNPs induced small lysosomal membrane destabilization (LMS EC50 = 273.1 µg/mL) and did not affect other immune parameters (phagocytosis and ROS production). Responses were little affected by hemolymph serum (HS) as exposure medium in comparison to ASW. However, AgNPs significantly affected mitochondrial membrane potential and actin cytoskeleton at lower concentrations. AgNO3 showed much higher toxicity, with an EC50 = 1.23 µg/mL for LMS, decreased phagocytosis and induced mitochondrial and cytoskeletal damage at similar concentrations. Both AgNPs and AgNO3 significantly affected Mytilus embryo development, with EC50 = 23.7 and 1 µg/L, respectively. AgNPs caused malformations and developmental delay, but no mortality, whereas AgNO3 mainly induced shell malformations followed by developmental arrest or death. Overall, the results indicate little toxicity of AgNPs compared with AgNO3; moreover, the mechanisms of action of AgNP appeared to be distinct from those of Ag+. The results indicate little contribution of released Ag+ in our experimental conditions. These data provide a further insight into potential impact of AgNPs in marine invertebrates.

Cationic polystyrene nanoparticle and the sea urchin immune system: biocorona formation, cell toxicity, and multixenobiotic resistance phenotype.

In order to assess the impact of nanoplastics on marine species, polystyrene nanoparticles (PS NPs) have been largely used as model particles. Here we studied the effects of 50 nm amino-modified PS-NH2 on Mediterranean sea urchin Paracentrotus lividus immune system cells (coelomocytes) in the presence of celomic fluid (CF) and at different NP concentrations (1, 5, 10, and 25 µg mL-1) and experimental conditions (absence or presence of EDTA). PS-NH2 acquired a protein corona once incubated with CF, dominated by the toposome precursor protein (TPP). In short-term cultures, a significant concentration- and time-dependent decrease in lysosomal membrane stability and apoptotic-like nuclear alterations were observed in phagocytes upon exposure to PS-NH2 (10 and 25 µg mL-1) in CF but they resulted abolished in the presence of EDTA confirming the role of TPP in triggering PS-NH2-coelomocytes interaction and toxicity. PS-NH2 did not alter MXR phenotype but the observed dose-dependent decrease in calcein accumulation suggests the ability of PS-NH2 to affect pump's efflux activity. Overall results encourage additional studies on positively charged nanoplastics, since the observed effects on sea urchin coelomocytes as well as the TPP corona formation might represent a first step for addressing their impact on sensitive marine species.

Differential diagnosis between a granuloma and radicular cyst: effectiveness of magnetic resonance imaging.

AIM: To investigate the diagnostic reliability and accuracy of magnetic resonance imaging (MRI) to differentiate periapical lesions of endodontic origin and to compare the results with histopathological information. METHODOLOGY: The radiolucent periapical jaw lesions of 34 patients, which were surgically enucleated, were investigated by two radiologists using MRI, based on the same six criteria, to categorize the lesions as granulomas, radicular cysts or others. After apicoectomies, two oral pathologists (blinded to the radiologist's diagnoses) analysed all specimens by referring to seven specific parameters and diagnosed the specimens as granulomas, radicular cysts or other conditions. The inter-rater agreements between the radiologists and pathologists in terms of MRI and histological diagnoses, respectively, along with the discriminant power of the adopted criteria and the accuracy of the MRI assessments compared with the histopathological results, were calculated. Cohen's kappa test was adopted to examine inter-rater agreement between the two radiologists and two pathologists. Guttman's lambda coefficient (λ6 ) was used to evaluate the internal consistency of the items used for the differential diagnosis by radiologists. The accuracy resulted from a receiver operator characteristic (ROC) analysis. RESULTS: A strong inter-rater reliability was observed between the two radiologists (k-statistic = 0.86, P = 0.0001) and the two pathologists (k-statistic = 0.88, P = 0.0001). The internal consistency of the diagnostic items was 0.605 for cysts and 0.771 for granulomas. The accuracy (true positives plus true negatives) of the radiologists was greater than that of the pathologists based on analysis (area under the curve = 0.87 and 0.91, respectively). CONCLUSIONS: The reliability and accuracy of MRI were high and comparable to histopathological reliability, highlighting the usefulness of this noninvasive technique as a pre-treatment diagnostic method for periapical endodontic lesions.

Cytotoxicity of CeO2 nanoparticles using in vitro assay with Mytilus galloprovincialis hemocytes: Relevance of zeta potential, shape and biocorona formation.

Over the last decades, the growth in nanotechnology has provoked an increase in the number of its applications and consumer products that incorporate nanomaterials in their formulation. Metal nanoparticles are released to the marine environment and they can interact with cells by colloids forces establish a nano-bio interface. This interface can be compatible or generate bioadverse effects to cells. The daily use of CeO2 nanoparticles (CeO2 NPs) in industrial catalysis, sunscreen, fuel cells, fuel additives and biomedicine and their potential release into aquatic environments has turned them into a new emerging pollutant of concern. It is necessary to assess of effects of CeO2 NPs in aquatic organisms and understand the potential mechanisms of action of CeO2 NP toxicity to improve our knowledge about the intrinsic and extrinsic characteristic of CeO2 NPs and the interaction of CeO2 NPs with biomolecules in different environment and biological fluids. The conserved innate immune system of bivalves represents a useful tool for studying immunoregulatory responses when cells are exposed to NPs. In this context, the effects of two different CeO2 NPs with different physico-chemical characteristics (size, shape, zeta potential and Ce+3/Ce+4 ratio) and different behavior with biomolecules in plasma fluid were studied in a series of in vitro assays using primary hemocytes from Mytilus galloprovincialis. Different cellular responses such as lysosome membrane stability, phagocytosis capacity and extracellular reactive oxygen species (ROS) production were evaluated. Our results indicate that the agglomeration state of CeO2 NPs in the exposure media did not appear to have a substantial role in particle effects, while differences in shape, zeta potential and biocorona formation in NPs appear to be important in provoking negative impacts on hemocytes. The negative charge and the rounded shape of CeO2 NPs, which formed Cu, Zn-SOD biocorona in hemolymph serum (HS), triggered higher changes in the biomarker of stress (LMS) and immunological parameters (ROS and phagocytosis capacity). On the other hand, the almost neutral surface charge and well-faceted shape of CeO2 NPs did not show either biocorona formation in HS under tested conditions or significant responses. According to the results, the most relevant conclusion of this work is that not only the physicochemical characterization of CeO2 NPs plays an important role in NPs toxicity but also the study of the interaction of NPs with biological fluids is essential to know it behavior and toxicity at cellular level.

Interactive effects of nanoparticles with other contaminants in aquatic organisms: Friend or foe?

The increasing production and use of nanoparticles (NPs) will lead to their release into the aquatic environment, posing a potential threat to the health of aquatic organisms. Both in the water phase and in the sediments NPs could mix and interact with other pollutants, such as organic xenobiotics and heavy metals, leading to possible changes in their bioavailability/bioconcentration/toxicity. However, whether these interactive effects may lead to increased harmful effects in marine organisms is largely unknown. In this work, available data mainly obtained on carbon based NPs and n-TiO2, as examples of widespread NPs, in aquatic organisms are reviewed. Moreover, data are summarized on the interactive effects of n-TiO2 with 2,3,7,8-TCDD and Cd(2+), chosen as examples of common and persistent organic and inorganic contaminants, respectively, in the model marine bivalve Mytilus. The results reveal complex and often unexpected interactive responses of NPs with other pollutants, depending on type of contaminant and the endpoint measured, as well as differences in bioaccumulation. The results are discussed in relation with data obtained in freshwater organisms. Overall, information available so far indicate that interactive effects of NPs with other contaminants do not necessarily lead to increased toxicity or harmful effects in aquatic organisms.

SEM, TEM, and IHC Analysis of the Sinus Node and Its Implications for the Cardiac Conduction System.

More than 100 years after the discovery of the sinus node (SN) by Keith and Flack, the function and structure of the SN have not been completely established yet. The anatomic architecture of the SN has often been described as devoid of an organized structure; the origin of the sinus impulse is still a matter of debate, and a definite description of the long postulated internodal specialized tract conducting the impulse from the SN to the atrioventricular node (AVN) is still missing. In our previously published study, we proposed a morphologically ordered structure for the SN. As a confirmation of what was presented then, we have added the results of additional observations regarding the structural particularities of the SN. We investigated the morphology of the sinus node in the human hearts of healthy individuals using histochemical, immunohistochemical, optical, and electron microscopy (SEM, TEM). Our results confirmed that the SN presents a previously unseen highly organized architecture.

Interactions between Mytilus galloprovincialis hemocytes and the bivalve pathogens Vibrio aestuarianus 01/032 and Vibrio splendidus LGP32.

Marine bivalves can accumulate large numbers of bacteria, in particular Vibrio species, whose persistence in bivalve tissues largely depends on their sensitivity to the bactericidal activity of circulating hemocytes and hemolymph soluble factors. The interactions between vibrios and hemolymph have been investigated, in particular in bivalve species susceptible to infection by certain Vibrio spp. and strains. In this work, the effects of two bivalve pathogens, Vibrio splendidus LGP32 (V.s.) and Vibrio aestuarianus 01/032 (V.a.), isolated from oyster mortality outbreaks, on the hemocytes of Mytilus galloprovincialis were investigated. In vitro, V.s., but not V.a., induced a dramatic decrease in lysosomal membrane stability-LMS in the hemocytes; both vibrios induced a moderate lysozyme release, with V.s. > V.a.. The V.s.-induced decrease in LMS was mediated by activation of PI-3Kinase, as shown by use of different kinase inhibitors. TEM analysis showed rapid internalization of both vibrios; however, V.s. lead to cellular and lysosomal damage and was able to survive within the hemocytes, whereas significant killing of V.a. was observed. In vivo, in mussels challenged with either vibrio and sampled at 6, 24 and 96 h post-injection, transient decreases in hemocyte LMS and progressive increases in serum lysozyme activity were observed, with V.s. > V.a.. Moreover, whereas V.a. was efficiently cleared from hemolymph, V.s. showed significant growth, that was maximal at 24 h p.i. when lowest LMS values were recorded in the hemocytes. Both vibrios also induced significant decreases in LMS in the digestive gland, again with V.s. > V.a.. The results indicate distinct interactions between mussel hemocytes and the two vibrio strains tested. The effects of V.s. may be due to the capacity of this strain to interfere with the signaling pathways involved in hemocyte function, thus escaping the bactericidal activity of the host cell, as observed for certain mammalian pathogens. Although V.s. is considered not pathogenic to Mytilus, this vibrio strain can affect the lysosomal function at the cellular and tissue level, thus leading to stressful conditions.

[Two cases of small bowel ischemia due to unusual cause]. / Ischemia intestinale da cause inusuali. Presentazione di due casi.

The authors report 2 cases of small bowel ischemia due to unusual cause. In both cases, vasculopathy was the cause of ischemia, but with a different etiology. In the first case, a mesenteric inflammatory veno-occlusive disease, with striking features of extensive phlebitis and venulitis affecting the veins of the small intestine and mesentery, without arterial involvement of this district was observed and histological examination showed inflammatory lymphocytic infiltrates and myointimal hyperplasia of the veins. The second case affected by intestinal ischemia from secondary and multiple cholesterol embolism, the histological examination showed inflammatory infiltrates with (lymphocytes and granulocytes) in the vessels of submucosal mesenteric area, by loose intimal fibrosis incorporating cholesterol clefts. Both patients required surgical exploration with resection of ischemic bowel. In the second case laparoscopy was the initial approach which allowed to identify the extension of ischemia with special regard to the perforation. The ultimate diagnosis is possible only with histological examination. Clinically, patients show the general signs of intestinal ischemia with pain, vomiting and bloody diarrhea. Prognosis depends on the extension of the lesions and the early surgical treatment.

Elusive amines and primary headaches: historical background and prospectives.

Although the role of trace amines such as tyramine, octopamine and synephrine in the pathogenesis of migraine has been debated for decades, this issue remains still unresolved. In spite of a relevant body of work, the inability to demonstrate specific receptors for these compounds and the lack of sensitive non-radioactive methods for the detection of trace amines in biological samples have limited their investigation in humans. However, the recent identification of a new, large family of G protein-coupled receptors, some of which bind and are activated by trace amines, has focused renewed attention on these compounds. This discovery, together with the possibility of providing novel insights for evaluation of the pathophysiological role of trace amines in primary headaches, may offer new opportunities for pharmacological strategies acting on these receptors. In light of the new scientific background, this review outlines a historical perspective and summarizes evidence supporting a role of trace amines in the pathogenesis of migraine and cluster headache.

[Thoracic lymphadenopathy due to vascular transformation of lymph node sinuses associated with upper limb edema in a chronic hemodialysis patient with congestive heart failure]. / Linfoadenopatia toracica da trasformazione vascolare dei seni linfonodali associata con edema dell'arto superiore in un paziente in emodialisi con insufficienza cardiaca congestizia.

BACKGROUND: Vascular transformation of lymph node sinuses (VTLS) is a rare disorder characterized by transformation of lymph node sinuses into endothelium-lined capillary-like channels. This phenomenon was originally discovered by accident whilst examining regional lymph nodes draining cancer. However, it has been found in association with other conditions associated with lympho venous congestion and distension, such as congestive heart failure (CHF) or even lymphoadenopathy alone. CASE REPORT: We describe the clinical case of a male dialysis patient with CHF (secondary to ischemic-hypertensive cardiac failure) who developed gross edema of the upper left limb on the arteriovenous fistula (AVF) side. Edema appeared within a month after carotid endoarteriectomy following approximately twenty years of chronic hemodialysis. Doppler ultrasound with other investigations showed that subclavian and upper cava veins were patent, but revealed many enlarged lymph nodes in the upper left thorax and in the left axilla. Suspicion of lymphoproliferative disease or metastatic involvement was raised and a lymph node biopsy was performed, revealing VTLS. Bone marrow biopsy and abdominal tomographies showed no mass or a proliferative disorder. Based on a hypothesis of an association between upper limb edema and ipsilateral AVF, the AVF was tied. The upper limb edema decreased dramatically within weeks, whilst RRT was continued by means of a central venous catheter. However, a few months later the patient's condition worsened; he developed relapsing pleural effusions and eventually died. Post-mortem examination revealed severe ischemic-calcific cardiopathy and showed that major thoracic and brachial vessels were patent whilst most thoracic and hilar lymph nodes showed VTLS and fibrosis. CONCLUSIONS: We believe that in our patient CHF was the primary cause of thoracic adenomegaly and that CHF, together with venous hypertension at the left fistula's arm, caused ipsilateral limb edema. Thus, adenomegaly due to VTLS could represent an accompanying feature even in upper limb edema in chronic hemodialysis patients. To our knowledge, this is the first report of such an association. In our patient months were "lost" because we thought that limb edema was secondary to the adenomegaly. It is important that clinicians working in dialysis units are aware that when upper limb edema is present, adenomegaly might just be an accompanying symptom, especially in case of concomitant diagnosis of CHF.

Esophagogastroduodenoscopy in chronic hemodialysis patients: 2-year clinical experience in a renal unit.

INTRODUCTION: Upper gastrointestinal (UGI) disorders are frequent in uremic patients and esophagogastroduodenoscopy (OGD) is an important investigation for their management. SUBJECTS AND METHODS: From January 1, 1997 to December 31, 1998, 57 endoscopies were performed in 96 hemodialysis patients (aged 65+/-12 years, 68 M, 28 F, dialysis duration 51+/-58 months) chronically treated in our unit in that period. The reasons for prescribing OGD were: anemia, after exclusion of poor response to EPO, in 26 patients (mean decrease in hemoglobin (Hb) levels 2.6+/-1.3 g/dl: the reference Hb level was the mean value measured before Hb decrease), dyspepsia in 11 and in preparation for renal transplantation in 20 patients. Twelve patients were diabetics, 24 smokers, 41 alcohol drinkers, 13 had hepatitis B or C, 6 were non-steroidal anti-inflammatory drugs (NSAIDs) abusers for bone pain and 21 were taking H2 receptor antagonists or proton-pump inhibitors chronically. Multiple biopsies of gastric mucosa were performed in 38 patients. RESULTS: Endoscopy revealed normal mucosa in 17.5% of cases, whilst chronic gastritis was diagnosed in 30%. Chronic gastritis was also the commonest microscopic abnormality diagnosed in 71.5% of biopsies. Anemic and non-anemic patients were matched and the 2 groups did not show significant differences in endoscopic findings and histological appearance. Thirteen patients had Helicobacter pylori (HP) infection demonstrated by biopsy specimen examination and were treated by metronidazole, clarithromycin and omeprazole. A logistic regression analysis was carried out in all subjects, considering the decrement in Hb as a dependent variable and demographic and clinical characteristics as independent variables. The analysis demonstrates that age (odds ratio 1.05; p < 0.05), NSAIDs abuse (odds ratio 15.6; p < 0.05) and HP infection (odds ratio 16.7; p < 0.01) were independently related to Hb decrease. CONCLUSIONS: In our experience, non-EPO-related anemia and dyspepsia are frequent features in hemodialysis patients. OGD is frequently requested (30% of patients/year) and 83% of patients investigated had abnormal UGI mucosa. Underlying mucosal inflammation might promote UGI bleeding but is not likely to be the cause, making it a necessary superimposed factor such as NSAIDs or HP infection.

Myocyte cellular hypertrophy is responsible for ventricular remodelling in the hypertrophied heart of middle aged individuals in the absence of cardiac failure.

OBJECTIVE: The aim was to measure changes in the numbers and size of ventricular myocytes in human hearts with marked ventricular hypertrophy and no clear signs of cardiac failure, to determine whether myocyte cellular hypertrophy is the only factor involved in the increase in cardiac mass. METHODS: Morphometric techniques were applied to estimate the number of myocyte nuclei per unit volume of myocardium which, in combination with the determination of the volume percent of myocytes, allowed the computation of the average myocyte cell volume per nucleus and total number of myocyte nuclei in the ventricles. Subsequently, the volume fraction of replacement fibrosis in the tissue was assessed and absolute component volumes in the ventricles obtained. RESULTS: Eight hypertrophied human hearts, weight 561(SD 68) g, were collected at necropsy from hypertensive patients who died from non-cardiac causes and were compared with eight normal hearts, weight 387(37) g, obtained from healthy individuals who also died from non-cardiac causes. With cardiac hypertrophy, left and right ventricular weight increased by 53% and 57%, whereas myocyte cell volume increased by 112% and 84%, respectively. The disproportion between the increase in ventricular weight and the increase in myocyte volume was due to a 30% and 16% loss in left and right ventricular myocytes following hypertensive hypertrophy. Myocyte loss also provoked a 319% and a 188% increase in the amount of replacement fibrosis in the left and right ventricular myocardium. These tissue and cellular processes resulted in an expansion in ventricular mass which exceeded the thickening of the wall so that an increase in cavitary volume occurred in both ventricles. CONCLUSIONS: Myocyte cellular hypertrophy is responsible for ventricular hypertrophy in hypertensive cardiomyopathy in its compensated stage. Myocyte loss precedes the impairment in ventricular pump function and may be implicated in the initiation of ventricular maladaptation.