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Biomedical subjects

L Moro

Publications and source records attributed to L Moro.

At least 19 recordsLinked to original sources
PubMed2006

Dynamic swallowing study and radiation dose to patients.

PURPOSE: The purpose of this study was to define an optimal radiological procedure to evaluate the results of rehabilitation therapy for swallowing disorders and to calculate both the effective and organ dose to the patient to provide a measure of the radiation risk associated with the procedure. MATERIALS AND METHODS: In order to define the optimal radiological procedure, kerma-area product (KAP) measurements and evaluations of image quality in fluoroscopy and fluorography mode were made using dedicated phantoms. Twenty-two patients were included in the study, and the values of KAP, screening time and average voltage selected were individually recorded. The recorded KAP values were used to estimate radiation risk with the use of dedicated calculation software. RESULTS: Median, first and third quartiles of the KAP distribution were, respectively, 2.1, 1.5 and 2.7 Gy cm2, with a corresponding effective dose of 0.35, 0.26 and 0.46 mSv. A good correlation between KAP and exposure time was also found (R2=0.85). Exposure of the thyroid, which is inside the radiation field, accounts for the greatest share to the effective dose, with a calculated median dose of 6 mGy. CONCLUSIONS: With the defined radiological procedure, the obtained KAP values are lower than recorded doses in interventional radiology, and the corresponding values of entrance skin dose are lower than the threshold dose for deterministic effects. Considering the effective dose at the median KAP value, the probability for stochastic effects is shown to be low, at approximately 1 in 39,000.

Adult↗
PubMed2006

Gastrointestinal transit, release and plasma pharmacokinetics of a new oral budesonide formulation.

AIMS: The aims of the study were to: (1) evaluate the gastrointestinal transit, release and absorption of budesonide from tablets with a new multimatrix formulation (MMX) designed to release the drug throughout the whole colon, and (2) assess the influence of food on budesonide bioavailability. METHODS: Two phase I studies, each comprising 12 healthy males, were performed. Gastrointestinal transit of (153)Sm-labelled tablets containing 9 mg budesonide was evaluated by means of pharmaco-scintigraphy. The effect of food was tested by comparing plasma pharmacokinetics after intake of a high fat and high calorie breakfast with fasting controls. RESULTS: (153)Sm-labelled tablets reached the ascending colon after a mean +/- SD 9.8 +/- 6.9 h. Initial tablet disintegration was observed in the ileum in 42% and the ascending and transverse colon in 33% of subjects. Ninety-six per cent of the dose was absorbed into the systemic circulation during passage through the whole colon including the sigmoid. Food significantly decreased C(max) values from 1429 +/- 1014 to 1040 +/- 601 pg mL(-1) (P = 0.028) and AUC values from 14 814 +/- 11 254 to 13 486 +/- 9369 pg h(-1) mL(-1) (P = 0.008). Mean residence time and t(max) increased by 12-29%. There was no drug accumulation after 1 week of once daily oral administration of budesomide. CONCLUSIONS: MMX-budesonide tablets appear suitable for targeted colonic drug delivery. Transit parameters and low systemic bioavailability warrant further studies with the new formulation.

Absorption↗
PubMed2006

Cellular proliferation, differentiation and apoptosis in polyether-polyurethane sponge implant model in mice.

The integration of implanted material to host organism requires spatial and temporal organization of several cellular processes, such as proliferation, differentiation and apoptosis. Despite the clinical relevance of these processes, there is little information regarding the sequence of such events in synthetic matrices. Here, we present a combination of techniques used to characterize the fibrovascular response in subcutaneous polyether-polyurethane sponge implants in mice at days 4, 7, 10 and 14 postimplantation. The AgNOR technique was modified and used as a surrogate marker for proliferating and activated cells invading the implant. The number of AgNOR-stained cells increased progressively from day 4 (606+/-76) to day 14 (2146+/-71) postimplantation. The number of TUNEL-positive (apoptotic index) cells also increased progressively from day 4 (459+/-40) to day 14 (1157+/-119) postimplantation. However, the ratio of TUNEL-labeled/proliferating cells had its highest peak in the early phase of the process remaining stable until day 14. Using Picrosirius staining it was shown that thin collagen increased from day 4, peaking at day 10 and falling markedly at day 14, whereas dense collagen increased progressively during the whole period. These experiments hold potential to investigate not only distinct phases of tissue repair induced by synthetic matrices but also to study underlying mechanisms involved.

Animals↗
PubMed2005

Membrane and extracellular antigens of Paracoccidioides brasiliensis (Mexo): identification of a 28-kDa protein suitable for immunodiagnosis of paracoccidioidomycosis.

In this work, we analyzed serological responses of paracoccidioidomycosis (PCM) patients to membrane and extracellular antigens (Mexo) of Paracoccidioides brasiliensis by ELISA, immunoblot technique and immunofluorescence assays to identify a specific antigen profile. Among 140 PCM serum samples analyzed, a homogeneous IgG response to Mexo was observed. The specificity of this antigen was 96.6% in relation to control sera and 81.2% to sera from patients with diverse infections. Patients undergoing treatment for more than 1 year showed a reduced antibody response against Mexo. These results suggest that the presence of anti-Mexo antibodies might be an indicator of active disease. A protein from Mexo with a molecular weight of 28 kDa (Pb28) was the most specific antigen in humoral immune responses to PCM, since it reacted with 100% of patient sera and did not react with heterologous serum samples tested. This protein was purified by molecular filtration chromatography in FPLC system and, when tested by immunoblotting, it maintained its reactivity and specificity of 100% with PCM sera. The Pb28 N-terminal amino acid sequence comparison analysis in the non-redundant GenBank database at NCBI revealed no significant homology to known PCM proteins or to other fungal proteins of known function. Since the 28-kDa protein of P. brasiliensis seems to be specific for PCM, it can be used as an alternative antigen in immunoblotting diagnostic methods.

Adolescent↗
PubMed2005

Markers of bone turnover: biochemical and clinical perspectives.

Bone remodelling is a process by which bone grows and turns over. This process involves a series of highly regulated steps that depend on the interaction of two cell lineages, the osteoclasts and the osteoblasts. Information on metabolic activity of bone tissue are achieved with the determination, in blood and in urine, of biochemical products derived from the activity of this cells. The ability to determine bone turnover with biochemical markers has been enhanced considerably in recent years with the development of new assays for more sensitive and specific markers. These new markers can now replace the outdated and non-specific markers of bone remodeling such as serum total alkaline phosphatase (ALP) and urinary hydroxyproline (Hyp) determination. Biochemical markers of bone turnover can be classified according to the process that underlie in markers of bone formation, products of the osteoblast activity [bone ALP, osteocalcin (OC), procollagene I C- and N-terminal propeptides] and markers of bone resorption, products of the osteocalst activity [pyridinuim crosslinks, collagen I C- and N-terminal telopeptides (CTX-I and NTX-I), tartrate resistent acid phosphatase (TRACP) isoform 5b]. The interpretation of laboratory results should always include the consideration of potential sources of variability. Variation in the results of biochemical markers of bone metabolism can compromise their ability to characterize disorders of bone metabolism. Variation can be categorized into pre-analytical, analytical and biological sources. However, the determination of biochemical markers of bone turnover offers many advantages in clinical practice, since they are non-invasive, can be repeated often, and major changes occur in a short time.

Acid Phosphatase↗
PubMed2004

Integrin regulation of epidermal growth factor (EGF) receptor and of EGF-dependent responses.

Integrin signalling co-ordinates with signalling originating from growth factor receptors in the co-operative control of cell proliferation, survival and migration. Increasing evidence suggests that integrins form physical complexes at the cell membrane with growth factor receptors, giving rise to signalling platforms at the adhesive sites. It is probable that at these sites integrins regulate adhesion and at the same time physically constrain and direct the response to soluble growth factors towards proliferation or survival stimuli. These co-operative effects might depend on integrin ability to activate growth factor receptors. In the present paper, we summarize our recent study showing that integrin-dependent adhesion triggers ligand-independent EGFR (epidermal growth factor receptor) activation to transduce downstream signalling. In addition, we also show that integrin-induced signalling pathways are necessary for EGF-dependent transcriptional response, demonstrating the requirement of the co-operation between cell-matrix adhesion and EGFR to achieve full biological responses.

Animals↗
PubMed2003

Apoptosis in canine distemper.

Canine distemper is a systemic viral disease characterized by immunosuppression followed by secondary infections. Apoptosis is observed in several immunosuppressive diseases and its occurrence on canine distemper in vivo has not been published. In this study, the occurrence of apoptosis was determined in lymphoid tissues of thirteen naturally infected dogs and nine experimentally inoculated puppies. Healthy dogs were used as negative controls. Samples of lymph nodes, thymus, spleen and brain were collected for histopathological purposes. Sections, 5 microm thick, of retropharingeal lymph nodes were stained by HE, Shorr, Methyl Green-Pyronin and TUNEL reaction. Shorr stained sections were further evaluated by morphometry. Canine distemper virus nucleoprotein was detected by immunohistochemistry. Retropharingeal lymph nodes of naturally and experimentally infected dogs had more apoptotic cells per field than controls. In addition, DNA from thymus of infected dogs were more fragmented than controls. Therefore, apoptosis is increased in lymphoid depletion induced by canine distemper virus and consequently play a role in the immunosuppression seen in this disease.

Animals↗
PubMed2003

Apoptosis in the cerebellum of dogs with distemper.

Canine distemper virus (CDV) may induce multifocal demyelination in the central nervous system of infected dogs. The pathogenesis of this process is not clear. The present work identifies the presence of apoptotic cells in white and grey matter of dogs'cerebellum, naturally infected with CDV. Fifteen dogs with clinical signs of canine distemper that tested positive for CDV nucleoprotein were used. Brain specimens were processed and embedded in paraffin. Sections 5 microm thick were stained with hematoxylin-eosin and Shorr. Other sections were submitted to TUNEL reaction and to immunohistochemistry for CDV nucleoprotein detection. Acute and chronic demyelinated plaques were observed in the white matter, while apoptosis occurred particularly in the granular layer of grey matter. Apoptosis seems to play an important role in the pathogenesis of canine distemper demyelination.

Animals↗
PubMed2001

Extracellular NAD(+) induces calcium signaling and apoptosis in human osteoblastic cells.

ADP-ribosyl cyclase/CD38 is a bifunctional enzyme that catalyzes at its ectocellular domain the synthesis from NAD(+) (cyclase) and the hydrolysis (hydrolase) of the calcium-mobilizing second messenger cyclic ADP ribose (cADPR). Furthermore, CD38 mediates cADPR influx inside a number of cells, thereby inducing Ca(2+) mobilization. Intracellularly, cADPR releases Ca(2+) from ryanodine-sensitive pools, thus activating several Ca(2+)-dependent functions. Among these, the inhibition of osteoclastic-mediated bone resorption has been demonstrated. We found that HOBIT human osteoblastic cells display ADP-ribosyl cyclase activity and we examined the effects of CD38 stimulation on osteoblasts function. Extracellular NAD(+) induced elevation of cytosolic calcium due to both Ca(2+) influx from the extracellular medium and Ca(2+) release from ryanodine-sensitive intracellular stores. Culturing these cells in the presence of NAD(+) caused a complete growth arrest with a time-dependent decrease of cell number and the appearance of apoptotic nuclei. The first changes could be observed after 24 h of treatment and became fully evident after 72-96 h. We propose a role of extracellular NAD(+) in bone homeostatic control.

ADP-ribosyl Cyclase↗
PubMed2001

Effects of cAMP on intercellular coupling and osteoblast differentiation.

Bone-forming cells are organized in a multicellular network interconnected by gap junctions. Direct intercellular communication via gap junctions is an important component of bone homeostasis, coordinating cellular responses to external signals and promoting osteoblast differentiation. The cAMP pathway, a major intercellular signal transduction mechanism, regulates osteoblastic function and metabolism. We investigated the effects of this second messenger on junctional communication and on the expression of differentiation markers in human HOBIT osteoblastic cells. Increased levels of cAMP induce posttranslational modifications (i.e., phosphorylations) of connexin43 and enhancement of gap junction assembly, resulting in an increased junctional permeance to Lucifer yellow and to a positive modulation of intercellular Ca(2+) waves. Increased intercellular communication, however, was accompanied by a parallel decrease of alkaline phosphatase activity and by an increase of osteocalcin expression. cAMP-dependent stimulation of cell-to-cell coupling induces a complex modulation of bone differentiation markers.

Alkaline Phosphatase↗
PubMed2001

Helium-Neon laser irradiation of hepatocytes can trigger increase of the mitochondrial membrane potential and can stimulate c-fos expression in a Ca2+-dependent manner.

BACKGROUND AND OBJECTIVE: To gain some insight into the photostimulation of isolated hepatocytes irradiated with Helium-Neon (He-Ne) laser light certain biochemical events were studied with respect to two mechanisms: i) the direct light dependent activation of certain biochemical events investigated in intact cells and isolated mitochondria, ii) the indirect stimulation of processes per se light independent. STUDY DESIGNS/MATERIALS AND METHODS: Irradiation of either isolated hepatocytes or isolated rat liver mitochondria was carried out with He-Ne laser (wavelength, 632.8 nm; fluence, 0.24 J cm-2; fluence rate, 12 mW cm-2). Changes in mitochondrial membrane potential in isolated hepatocytes were monitored using the cationic probe safranine. The c-fos expression was studied by Northern blot and immunoblot analysis. RESULTS: As a result of irradiation, increase of the mitochondrial membrane potential was found to occur in irradiated hepatocytes both in the presence or in the absence of CaCl2. The hyperpolarization of the mitochondrial membrane is assumed to cause an increase in mitochondrial Ca2+ uptake that was measured in isolated mitochondria. Finally, an increase in c-fos expression was found in irradiated hepatocytes when incubated in the presence of CaCl2. CONCLUSION: This paper gives additional information on the mechanism by which He-Ne laser light, either directly or in a cascade-like effect dependent on increase in cell Ca2+, can cause cell stimulation.

Animals↗
PubMed2001

Regulation of MCP-3 and BRCA2 mRNA expression levels by beta(1) integrins.

The integrin cytoplasmic domain has been shown to modulate several cellular functions, including cell proliferation, adhesion, migration, and intracellular signaling. The beta(1) integrin subunits beta(1C) and beta(1A), which contain variant cytoplasmic domains, differentially affect cancer and normal cell functions. To identify target genes selectively regulated by these beta(1) cytoplasmic variants, stable cell transfectants expressing either beta(1A) or beta(1C) under the control of a doxycycline-inducible promoter were obtained using murine beta(1)-deficient GD25 cells. Screening of 1176 murine cDNAs using first-strand cDNA of mRNA isolated from either beta(1C)- or beta(1A)-expressing cells showed a striking differential expression of few genes. The differential expression of two genes, MCP-3 and BRCA2 (monocyte chemoattractant protein-3 and breast cancer susceptibility gene 2, respectively), whose products are involved, respectively, in chemotaxis and embryonic proliferation, was confirmed by Northern blot analysis. Increased MCP-3 and decreased BRCA2 mRNA levels in cells expressing beta(1C) compared to those in cells expressing beta(1A) were observed. Since beta(1C) and beta(1A) stable cell transfectants showed comparable adhesion to fibronectin, upregulation of MCP-3 and downregulation of BRCA2 mRNA levels did not appear to be due to a differential ability of the beta(1C) cells to adhere to the beta(1) ligand fibronectin. Overall, our data show that beta(1) integrin cytoplasmic domain variants control expression of downstream target genes in a differential manner without affecting cell adhesion.

Animals↗
PubMed2001

Epitope-specific antibodies to the beta(1C) integrin cytoplasmic domain variant.

The beta(1C) integrin is an alternatively spliced variant of the beta(1) subunit that contains a unique 48-amino-acid sequence in its cytoplasmic domain. We have shown previously that beta(1C) is a potent inhibitor of cell proliferation and that in vivo its expression is downregulated in prostate and breast carcinoma. In this study, we describe a panel of specific monoclonal antibodies that react with the beta(1C) cytodomain. We show by immunoblot analysis that the newly generated monoclonal antibodies specifically recognize the beta(1C) cytodomain expressed as glutathione S-transferase fusion protein. The specificity of the antibodies to beta(1C) was confirmed in competition studies by immunoblotting using beta(1C)-specific synthetic peptides. These monoclonal antibodies reacted, in enzyme-linked immunosorbent assays, with the beta(1C) 785-808 peptide but failed to bind the beta(1C) 778-794, beta(1C) 805-825, or beta(1A) 765-798 peptides. Thus, the epitope recognized by the antibodies is located within the Q(795)-F(804) beta(1C) cytoplasmic sequence; this region overlaps the previously described Q(795)-Q(802) domain necessary for beta(1C) to inhibit cell proliferation. To our knowledge, these are the first monoclonal antibodies specific for a beta(1) cytoplasmic isoform. The monoclonal antibodies described here will be useful tools for dissecting functional differences, among beta(1) integrin variants, as well as for the study of the role of beta(1C) in prostate and breast epithelial cell proliferation.

Amino Acid Sequence↗
PubMed2001

Depression and torture.

Torture represents an exceptionally traumatic experience in which horror, helplessness, and hopelessness are extreme. Therefore, it can be expected that depression, along with other trauma-related disorders is present in torture victims at higher rates than in other psychotraumatized individuals. To demonstrate this, we examined two groups of refugees, all suffering the post-traumatic stress disorder. The first group (N = 50) had combat experience but were imprisoned and tortured as well. Members of the second group (N = 29) had combat experience. A third group (N = 30) consisted of local people with no traumatic experience. Using the Hamilton scale, the Beck Depression Inventory and structured dedicated interviews, we tried to determine whether those groups differed in level of depression based on their different levels of traumatic experience. The results of our study indicate that torture victims showed a significantly higher level of depression that is clinically relevant.

Adult↗
PubMed2001

Stressor characteristics and post-traumatic stress disorder symptom dimensions in war victims.

AIM: To evaluate how the type of trauma is related to specific symptom patterns in patients with post-traumatic stress disorder (PTSD) according to the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria. METHODS: A total of 136 PTSD patients exposed to war-related traumatic experiences were divided in four groups: 79 veterans, 18 former prisoners (who witnessed or were subject to torture or frequent assaults), 15 victims of rape, and 24 refugees from Bosnia and Herzegovina. Each group was homogenous in regard to traumatic experiences. RESULTS: Significant inter-group differences were found in symptoms listed in the DSM-IV criteria, and under criteria C (avoidance) and D (arousal). No such differences were observed in symptoms listed under criterion B (intrusive symptoms). The results indicate that stressor characteristics may play a role not only in the variety of symptoms exhibited, but particularly in the number of avoidance and arousal symptoms. Victims of rape tended to present with more avoidance symptoms and fewer hyperarousal symptoms, whereas former prisoners and veterans tended to report more hyperarousal symptoms. Rape victims and former prisoners also reported more symptoms than the other groups. CONCLUSION: There is a strong indication that stressor characteristics influence the variety and number of exhibited intrusive, avoidance, and arousal symptoms. More research is needed to precisely define individual symptom dimensions possibly relating to particular stressor characteristics. Additional studies are needed to determine whether PTSD, as it is currently defined in the DSM-IV, is really a homogenous diagnostic category.

Adult↗
PubMed2001

Changes of cytolytic cells and perforin expression in patients with posttraumatic stress disorder.

AIM: To define phenotypic characteristics of cytotoxic T lymphocytes (CTL) and natural killer cells (NK) in peripheral blood, frequency of somatic symptoms, and level of anxiety and depression in 25 patients clinically diagnosed with chronic post-traumatic stress disorder (PTSD). METHODS: Patients were divided into two sub-groups according to the stressor: 18 PTSD patients with the battlefield experience and 7 PTSD patients with battlefield experience who were tortured as the prisoners of war (POW) in Bosnian-Serbian camps. The control group consisted of 15 healthy volunteers matched to the patients by sex and age. We tested all patients using Becks depression inventory, Spielberger anxiety test, and somatic disturbance list, and analyzed their peripheral blood lymphocytes using flow cytometry with the double fluorescence staining of cell surface antigens (CD3, CD4, CD8, CD16, and CD56) and intracellular cytolytic molecule perforin (P), a mediator of cytolytic action at the molecular level. RESULTS: All PTSD patients showed a significant level of anxiety, depression, and numerous somatic symptoms. The only significant difference between PTSD patients with and without POW experience was in the anxiety level (median, 71; range 61-79; vs median, 65; range, 49-77). PTSD patients with POW experience had significantly higher levels of CD16+ cells (median, 37%; range, 16-55%) than those without it (median, 12%; range, 5-37%). Double labeling for intracellular P antigen and cell surface antigens showed the highest levels of CD16+P+ (median, 33%; range, 15-40%; vs median, 10%; range, 3-29%) and CD56+P+ (median, 21%; range, 11-40%; vs median 8%; range, 1-30%) cells in PTSD-POW patients. CONCLUSION: Chronic PTSD patients who survived concentration camps show the most numerous alterations in PBL phenotype, the highest number of perforin-containing cells, and a significantly higher level of anxiety.

Adult↗
PubMed2001

[Single-slice and multi-slice computerized tomography: dosimetric comparison with diagnostic reference dose levels].

PURPOSE: The absorbed dose during clinical examinations of the head, thorax, abdomen and pelvis performed with a single-slice CT scanner and a new multi-slice CT system was measured and compared. Technical parameters, defined at installation and memorized on the two CT machines relate to a standard-sized patient and were considered the reference standard. Our experimental data were also been compared with the Diagnostic Reference Levels (D.L. 26/5/2000 n.187, Annex V). MATERIAL AND METHODS: We compared the performance of a multi-slice GE LightSpeed QX/i ADVANTAGE to that of a single-slice GE ProSpeed SX. The radiation beam profiles were measured at isocenter using a phosphor plate. Dose measurements were performed, according to the EUR 16262 EN Guidelines, with a 10-cm long CT pencil ionisation chamber and two PMMA phantoms (CEI EN 61223-2-6) for head and body respectively. RESULTS: The obtained (normalised and weighted) computed tomographic dose index (nCTDIW) values were systematically higher for the multi-slice system (up to 36%) and the dose-length product (DLP) values on the multi-slice scanner exceeded the equivalent single-slice DLP values. The values were, however, always lower than DRLs, except in the case of the head multi-slice protocol, the technical parameters of which need to be improved. Our results allowed moreover to calibrate the automatic dose evaluation system of the multi-slice system, which systematically underestimated DLP values. DISCUSSION AND CONCLUSIONS: The comparison showed that the multi-slice scanner delivers a higher dose compared to the single-slice scanner. This is due to the radiation beam profile which is wider than the total active detector width, to the shorter focal spot-to-isocenter distance and to the effective scan length, which is longer than the nominal irradiated volume because the reconstruction algorithm of a multi-slice helical CT image requires the projection data from all detector rows. Nevertheless, the technology of new CT systems equipped with a multiple row detectors array can improve the protection of the patient thanks to very short irradiation time (less than 1 s) and reduced current values. In order to optimize the dose to the patient some acquisition parameters have been adjusted for head examinations.

Radiation Dosage↗