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Biomedical subjects

A D'Alessandro

Publications and source records attributed to A D'Alessandro.

At least 19 recordsLinked to original sources

Percutaneous radiofrequency thermal ablation for hepatocellular carcinoma.

BACKGROUND: Radiofrequency thermal ablation is the first therapeutic option in percutaneous treatment of hepatocellular carcinoma but data on its long-term efficacy and safety are not conclusive. AIM: This study reports a prospective survey on radiofrequency thermal ablation in north-east Italy. METHODS: Data were collected on 401 patients with hepatocellular carcinoma (males 301, mean age: 68 years) treated by radiofrequency thermal ablation in 13 centres. Indication to treatment was: single nodule not eligible for surgery in 77% of patients, 2-3 nodes in 18% and multiple lesions in 5%. Mean size was 3 cm (1-8 cm). Treatment response was assessed at 1 month by spiral computerized tomography and then with ultrasound examination and new spiral computerized tomography. RESULTS: Complete response was obtained in 67% of patients and in 27% response was 75-99%. Complete response raised to 77% in lesions smaller than 3 cm. The morbidity rate was 34%; the mortality was 0.5%, seeding was observed in four patients. Ten patients presented an unexpected rapid disease progression. CONCLUSION: The above data show that by radiofrequency thermal ablation, complete response can be achieved only in about two-third of the cases, clearly less than expected, and that, beyond seeding, unexpected progression can be observed.

Aged↗

[New antiarrhythmic drugs for therapy of atrial fibrillation: II. Non-ion channel blockers].

The therapeutic approach to atrial fibrillation is difficult and challenging. The effect of "classical" antiarrhythmic agents is based on their inhibitory effects on various ion channels. However, therapeutic benefit of these agents is often limited. The primary goal of this article is to discuss new therapeutic approaches using non-ion channel blocking drugs in the treatment of atrial fibrillation. Some of the substances discussed in this article have been used already in the clinical practice. Others, for example gentherapeutic approaches, are still in the experimental state. In contrast to ion channel blocking agents their efficacy is based on the suppression of structural remodeling. Hence, it can be assumed that due to these effects they may also be beneficial in the primary prevention of atrial fibrillation.

Angiotensin II↗

Elemental characterization of PM10, PM2.5 and PM1 in the town of Genoa (Italy).

The particulate matter (PM) concentration and composition, the PM10, PM2.5, PM1 fractions, were studied in the urban area of Genoa, a coastal town in the northwest of Italy. Two instruments, the continuous monitor TEOM and the sequential sampler PARTISOL, were operated almost continuously on the same site from July 2001 to September 2004. Samples collected by PARTISOL were weighted to obtain PM concentration and then analysed by PIXE (particle induced X-ray emission) and by ED-XRF (energy dispersion X-ray fluorescence), obtaining concentrations for elements from Na to Pb. Some of the filters used in the TEOM microbalance were analysed by ED-XRF to calculate Pb concentration values averaged over 7-30 d periods.

Air Pollutants↗

Chromosome fragility in two sheep flocks exposed to dioxins during pasturage.

In the last 3 years several farms raising cattle, river buffalo and sheep have been unable to sell dairy milk due to the presence of high levels of dioxins. Furthermore, several cases of abortion (around 25% of total births) and abnormal foetuses (2.5% of total births) were recorded in two flocks of sheep raised in the province of Naples where a higher level of dioxins (5.27 pg/g fat, as human WHO TCDD equivalent) have been found in the milk mass than that permitted (3.0 pg/g fat, as human WHO TCDD equivalent). Cytogenetic investigations were carried out on 24 sheep (all females), randomly sampled from the two different flocks, one abnormal foetus and 11 female sheep (control) raised approximately 80 km from the area where the two exposed flocks were raised. Frequencies of aneuploid cells, gaps, chromatid breaks, chromosome breaks, fragments and sister chromatid exchange (SCE) were determined. While no differences were observed between the number of aneuploid cells (15% of total cell population) of both exposed animals and controls, significant (P < 0.001) increases in the frequencies of other chromosome abnormalities (mean chromosome abnormality/cell = 0.76 +/- 1.1) and SCEs (mean SCE/cell = 9.4 +/- 3.7) were found in the exposed animals, compared with the control (mean chromosome abnormality/cell = 0.18 +/- 0.4; mean SCE/cell = 7.1 +/- 3.0). Significantly higher values of SCEs (mean SCE/cell = 10.9 +/- 4.4) were also found in the abnormal foetus compared with the control. Chemical analyses on soil, grass and water at two sites where the two flocks were pastured established that doses of dioxins (17 different types) were below the legally permitted limits.

Aneuploidy↗

Erroneous reports of the neotropical Echinococcus oligarthrus as a cause of echinococcosis in India.

Two cases of submandibular echinococcosis have been reported in adult residents of India (Kini et al., 1997; Sahni et al., 2000). It was stated in both publications that the cestode was E. oligarthrus, "a rare variety of E. granulosus", based on morphogical characteristics. It was also mentioned that 3 cases of E. granulosus with similar submandibular metacestode had been previously diagnosed in India. The metacestode is readily distinguishable from that of E. oligarthrus. The final hosts of E. oligarthrus are several neotropical species of wild cats and metacestode occurs in hystricognath, all of them absent in India. The larval stage of all 4 species of Echinococcus can be differentiated on the basis of the form and dimensions of rostellar hooks of protoescoleces. With the information provided in the two papers we concluded that the 2 cases of echinococcosis described in India were due to E. granulosus.

Animals↗

Zoledronic acid induces antiproliferative and apoptotic effects in human pancreatic cancer cells in vitro.

Bisphosphonates (BPs) are an emerging class of drugs mostly used in the palliative care of cancer patients. We investigated the in vitro activity of the most potent antiresorptive BP, zoledronic acid (ZOL), on the growth and survival of three human pancreatic cancer (PC) cell lines (BxPC-3, CFPAC-1 and PANC-1). Pancreatic cancer frequently has a dysregulated p21(ras) pathway and therefore appears to be a suitable target for BPs that interfere with the prenylation of small GTP-binding proteins such as p21(ras). We found that ZOL induces growth inhibition (IC(50):10-50 micro M) and apoptotic death of PC cells. The proapoptotic effect was correlated to cleavage/activation of caspase-9 and poly(ADP)-ribose polymerase, but not of caspase-3. Moreover, we studied the p21(ras) signalling in cells exposed to ZOL and detected a reduction of p21(ras) and Raf-1 content and functional downregulation of the terminal enzyme ERK/MAPkinase and of the pKB/Akt survival pathway. Finally, we observed that ZOL induces significant cytoskeletal rearrangements. In conclusion, we demonstrated that ZOL induces growth inhibition and apoptosis on PC cells and interferes with growth and survival pathways downstream to p21(ras). These findings might be relevant for expanding application of BPs in cancer treatment.

Apoptosis↗

High prevalence of HCV infection among the general population in a rural area of central Italy.

The hepatitis C virus infection (HCV) is the most frequent cause of hepatic infection in Europe. In Italy, anti-HCV positivity values are extremely variable, depending on the age and geographic location of the population being analysed. The aims of the study were: (1) evaluating positivity for anti-HCV antibodies in various age groups and determining the HBsAg in a mountainous and predominantly farming area in central Italy; (2) assessing some anamnestic and clinical variables through a questionnaire, submitted during the taking of blood samples, in order to determine HCV exposure and risk factors for the target population. 344 subjects selected by random sampling among 3308 people, older than 16, were considered as the target population. A prevalence study was carried out. The sources of data were: blood samples taken to carry out the HCV positivity test; a questionnaire including items about exposures at risk and case-historical and clinical patient data. The risk of infection was evaluated by a multiple logistic regression model. The inferred HCV+ prevalence rate is 22.4/100 (95% confidence interval (CI): 20.8-24.1). An increasing age trend is shown with a higher positive predominance among females (28.99/100 vs. 14.29/100 in males). The positive HBsAg prevalence in the examined survey is 1.2/100. Variables associated with the HCV occurrence are case history of pneumonopathy (OR: 4.9) and exposure to parenteral therapies with glass syringes (OR: 3.3). This study is consistent with literature about the hypothesis of a north-south geographic gradient in the hepatitis C occurrence in Italy. Data clearly show the effects of the inappropriate use of medical or surgery practices on the population, with particular reference to the use of glass syringes. No elements prove that the farming features of the area may be predictive of HCV infection risk. The extent of the recorded prevalence values calls for the implementation of programmes aimed at detecting clusters or population areas at risk.

Adult↗

Yellow nail syndrome: does protein leakage play a role?

Yellow nail syndrome is characterized by primary lymphoedema, recurrent pleural effusion and yellow discoloration of the nails. Although mechanical lymphatic obstruction is assumed to be the underlying pathology, it cannot explain the common finding of high albumin concentration in the pleural space. This paper describes a case of yellow nail syndrome presenting with the classical triad of lymphoedema, recurrent pleural effusion and yellow discoloration of the nails, associated with persistent hypoalbuminaemia and increased enteric loss of albumin. Based on the findings in this case and those in the literature, it is speculated that increased microvascular permeability may contribute to the pathogenesis of this syndrome.

Aged↗

Silica and its antagonistic effects on transforming growth factor-beta in lung fibroblast extracellular matrix production.

BACKGROUND: Silicosis, a pneumoconiosis marked by interstitial pulmonary fibrosis, is caused by inhalation of free crystalline silica particles. When silica particles are injected into the lower lung, they are translocated across the epithelium into the interstitial space, where macrophage-derived growth factors affect lung fibroblast proliferation and collagen deposition. We hypothesized that silica may act directly on pulmonary fibroblasts modifying extracellular matrix (ECM) synthesis and that the effects of silica may be mediated by transforming growth factor-beta (TGFbeta) overproduction. METHODS: To test this hypothesis, we studied a human lung fibroblast cell line (WI-1003) exposed to silica in vitro. We investigated cell morphology by electron microscopic procedure, cell growth, collagen production, and glycosaminoglycans (GAG) composition by radiolabeled precursors. Cytokine and growth factor synthesis were evaluated by specific enzyme-linked immunoadsorbent assay kits and Northern blotting analysis. RESULTS: Pulmonary fibroblasts internalized silica particles without detectable cell damage. Silica directly stimulated collagen synthesis and decreased the amount of 3H-glucosamine-labeled GAG. Silica-treated fibroblasts secreted less TGFbeta than untreated controls, antagonized the stimulatory effect of TGFbeta on ECM synthesis, and reversed TGFbeta-induced inhibition of cell proliferation. Northern blotting analysis showed increased interleukin-1alpha (IL-1alpha) mRNA after silica treatment. IL-1alpha had no influence on collagen synthesis but increased the number of WI-1003 fibroblasts. CONCLUSIONS: These results support our hypothesis that lung fibroblasts are direct silica targets. However, contradicting our hypothesis, silica antagonized TGFbeta activities through a TGFbeta downregulation and an IL-1alpha upregulation. The complex pattern of TGFbeta and IL-1alpha regulation in pulmonary fibroblasts is imbalanced by silica exposure and might play a key role in silica-mediated pulmonary fibrosis.

Cell Division↗

Bronchial epithelial cell matrix production in response to silica and basic fibroblast growth factor.

BACKGROUND: Previous studies show that macrophages, lung fibroblasts, and their soluble mediators are responsible for the onset and development of pulmonary fibrosis. This study was conducted to determine whether airway epithelial cells are also directly involved in response to fibrogenic agents and consequently in the pathogenesis of lung fibrosis. To verify the hypothesis, we determined whether silica acts directly on human bronchial epithelial cells by stimulating cytokine and growth factor release and by modifying matrix production. MATERIALS AND METHODS: An SV40 large T antigen-transformed human airway epithelial cell line, 16HBE14o (16HBE), was used. The expression profile of some proinflammatory interleukins (ILs), such as IL-1alpha, IL-1beta and IL-6 and their modulation by silica, were evaluated by polymerase chain reaction (PCR) analysis. Transforming growth factor beta (TGFbeta) and basic fibroblast growth factor (bFGF) mRNA levels were tested by Northern blotting in the presence and in the absence of silica. The silica- and/or bFGF-induced effects on matrix components (total proteins, collagen, and fibronectin) were also evaluated using radio-labeled precursors. RESULTS: The results demonstrated 16HBE internalized silica particles. Silica induced a little IL-6 secretion, without affecting IL-1 and TGFbeta isoform production and strongly stimulated bFGF mRNA level and bFGF protein secretion. Silica also induced changes in 16HBE production of total proteins, collagen, and fibronectin production. When added in combination with the growth factor, it strengthened bFGF stimulation of matrix component secretion. CONCLUSIONS: These results support the hypothesis that the changes in matrix components are due to a direct effect of silica on bronchial epithelial cells. Silica-induced over-secretion of bFGF suggests that autocrine and paracrine differentiation loops for bFGF may also be operative and that these mechanisms may be involved in the pathogenesis of pulmonary fibrosis. In the future, cytokine-directed therapeutic strategies might find a place in clinical practice.

Blotting, Northern↗

Active immunization with a synthetic fragment of pig inhibin alpha-subunit increases ovulation rate and embryo production in superovulated ewes but season affects its efficiency.

Two experiments were designed to determine the effects of active immunization against one of two synthetic peptides from humans (inhibin-like peptide) or pigs (inhibin alpha-subunit) on antibody titres, ovulation rate and embryo production in ewes superovulated with 16 U ovine FSH. In Expt 1, during the breeding season, 30 ewes were subdivided into three groups: group I served as the non-immunized control; group II was immunized against inhibin-like peptide (100 micrograms inhibin-like peptide equivalent, followed by three booster injections); group III was immunized against pig inhibin alpha-subunit conjugated to human serum albumin (96 micrograms for the primary administration and 46 micrograms for the booster). In Expt 2, the efficiency of immunization against pig inhibin alpha-subunit on ovarian response and embryo production was evaluated during the non-breeding season in two groups of ewes (n = 12): group IV was a non-immunized control; Group V was immunized against pig inhibin alpha-subunit. During the breeding season, the ewes immunized against pig inhibin alpha-subunit showed higher antibody titres compared with the group immunized against inhibin-like peptide (P < 0.01) and a significant increase in ovulation rate (12.1) compared with both the control (5.0; P < 0.05) and the inhibin-like peptide-immunized group (3.1; P < 0.01). Immunization against pig inhibin alpha-subunit increased transferable embryo yield 4.5-fold (6.7 versus 1.5; P < 0.01) and improved embryo quality (94.6 versus 40.6%; P < 0.01). During the non-breeding season, immunization against pig inhibin alpha-subunit enhanced ovulation rate from 2.6 in the controls to 9.4 (P < 0.01) but did not affect transferable embryo production (3.9 versus 2.1; P > 0.05) and significantly lowered their quality (54.1 versus 100%; P < 0.01). In conclusion, active immunization against pig inhibin alpha-subunit can improve superovulatory response during the breeding season, while it appears to be unable to increase embryo yield during the seasonal anoestrus.

Anestrus↗

Histogenesis in the metacestode of Echinococcus vogeli and mechanism of pathogenesis in polycystic hydatid disease.

Histogenesis of the metacestode of Echinococcus vogeli was traced mainly in rodents inoculated intraperitoneally with finely minced infective vesicles. The fragments aggregated in the peritoneal cavity and coalesced, forming structures (plaques) from which primary vesicles arose. From primordia in their germinal tissue, exogenous vesicles developed, enlarged, and migrated outward to the surface of the laminated membrane, where they remained attached and proliferated. Each unit of vesicles so formed retained discrete identity and, within 6-8 mo, acquired an adventitia; thereafter, exogenous multiplication ceased and endogenous proliferation supervened. Large numbers of daughter cysts arose in the germinal tissue lining chambers within the units; endogenous proliferation also finally ceased, and the daughter cysts produced brood capsules containing protoscoleces. Primordia of exogenous vesicles were not observed in the walls of daughter cysts. Production of protoscoleces involved 3 processes: they developed in typical brood capsules, singly in minute brood capsules, or directly from germinal tissue. Exogenous proliferation is not characteristic in the natural intermediate host of E. vogeli, the paca. Evidently in primates, the initial proliferation in the liver is followed by extension of the metacestode into the peritoneal cavity and eventual invasion of abdominal and thoracic organs. Exogenous proliferation by a process unique to E. vogeli accounts for the clinical course of polycystic hydatid disease.

Animals↗

Optimal pH for simple cold storage or machine perfusion of dog kidneys with UW solution.

Metabolic suppression by temperature is a key to successful organ preservation. Additional methods for inducing metabolic suppression may further improve organ preservation. Extracellular acidosis has been shown to suppress warm anoxic injury to various isolated cells. Acidosis may suppress enzymes with a pH optimum at the pH of the cytosol (pH 7.3). In this study, the combination of hypothermia and acidosis was used to determine if it would improve renal preservation. Dog kidneys were cold-stored (CS) for 48 h in University of Wisconsin (UW) solution with the pH adjusted to 6.4, 6.8, 7.4, or 7.8. Kidneys were also machine-perfused (MP) for 3 days with the gluconate perfusion solution (Belzer's machine perfusion solution, MPS) at pHs similar to those tested for CS. Renal function (serum creatinine, SCr) and survival were recorded in immediate contralateral nephrectomized recipients. On the basis of maximum SCr values, kidneys preserved by CS or MP were best preserved at pHs of 7.4 or 7.8. At a pH of 6.8, SCr values were elevated and returned to normal at a slower rate than in those preserved at higher pHs. This study shows that acidosis is not cytoprotective to cold-stored dog kidneys and causes preservation/reperfusion injury.

Adenosine↗

Tumor necrosis factor-alpha and interleukin-8 release from U937 human mononuclear cells exposed to zinc oxide in vitro. Mechanistic implications for metal fume fever.

Respiratory exposure to zinc oxide results in metal fume fever, a flu-like illness characterized by dose-dependent increases in pulmonary tumor necrosis factor-alpha (TNF) and interleukin-8 (IL-8). To examine whether mononuclear cells are a source of these proinflammatory cytokines, we exposed U937 cells to zinc oxide in vitro. Cell culture supernatant TNF and IL-8 was measured after 3, 8, and 24 hours of exposure to zinc oxide in varying concentrations. Zinc oxide exposure in vitro led to TNF release in a dose-dependent manner at 3, 8, and 24 hours (analysis of variance [ANOVA] P = 0.0001). IL-8 demonstrated a statistically significant zinc exposure response at 8 hours (ANOVA P = 0.005) and 24 hours (ANOVA P = 0.02). IL-8 at 8 hours correlated with 3-hour TNF levels (r = 0.52, P = 0.04). These data demonstrate that in vitro zinc oxide exposure stimulates U937 mononuclear cells to release TNF and IL-8 consistent with in vivo observations in metal fume fever.

Cells, Cultured↗

Neotropical echinococcosis in Suriname: Echinococcus oligarthrus in the orbit and Echinococcus vogeli in the abdomen.

This paper reports two cases of neotropical echinococcosis caused by Echinococcus oligarthrus and E. vogeli, neither of which has been reported from Suriname. Case 1, a six-year-old boy, presented a 15 x 25 mm retro-ocular cystic tumor (observed by ultrasound, computed tomography scan, and magnetic resonance imaging) causing exophthalmia, chemosis, palpebral ptosis, and blindness of the left eye. Of two tentative diagnoses, Echinococcus cyst or dermoid tumor, the former was shown to be correct at surgery when a clear liquid and detached protoscoleces were aspirated. Rostellar hooks of the protoscolex were characteristic of E. oligarthrus. Case 2, a 41-year-old man, had polycystic masses excised from the liver and abdomen. A presurgery diagnosis of E. vogeli infection was made due to calcifications seen in the lesions, positive serology, residence of the patient in the tropical forest, and later by the size and shape of rostellar hooks. The presence of these two parasites in one of the former Guianas is not surprising; both species are endemic in tropical forest in Central and South America wherever people have not exterminated wild canids, especially the bush dog, (Speothos venaticus), and felids (wild cats of several species), along with pacas, agoutis, and other rodents that serve as intermediate host of these two cestodes. Eighty-six cases of polycystic echinococcosis are known in people from 11 countries from Nicaragua to Argentina: 32 due to E. vogeli, three to E. oligarthrus, and 51 for which determination of the species was not possible because the hooks of the protoscolex were not found or described. Research to elucidate aspects of transmission of E. vogeli and E. oligarthrus is of practical importance for defining measures for preventing the severe and frequently fatal illnesses caused by these two cestodes.

Abdomen↗

A cryptic protease activity from Trypanosoma cruzi revealed by preincubation with kininogen at low temperatures.

Cysteine proteases have been identified in parasitic protozoa including the causative agent of Chagas' disease Trypanosoma cruzi. T. cruzi lysates subjected to substrate-containing SDS-polyacrylamide gel electrophoresis exhibit major bands of proteolytic activity in the 45-55 kDa molecular mass range (cruzipain activity). Paradoxically, addition of kininogen (a cystatin-like protease inhibitor) to the lysates before electrophoresis results in the appearance of additional bands of proteolytic activity in the 160-190 kDa molecular mass range. This inhibitor-activated protease activity depends upon the reaction conditions and exhibits novel properties. For example, a 24-48 hour preincubation at low temperature (-20 degrees C optimum) greatly enhances the proteolytic activity. The results suggest that a metastable complex forms between kininogen and a cryptic 30 kDa cysteine protease from T. cruzi and that this complex participates in the activation of proteolytic activity.

Animals↗

Polycystic echinococcosis in tropical America: Echinococcus vogeli and E. oligarthrus.

The paper reports available data on 72 known human cases of polycystic echinococcosis (PE) caused by Echinococcus vogeli (Ev) or E. oligarthrus (Eo). The patients' ages ranged from 6 to 78 years (median 44); one third were younger than 22 years and had severe lesions, demonstrating the aggressiveness of PE. There were no differences in occurrence between sexes. In 80% of the cases the lesions were in the liver alone or in combination with other organs; the rest were located in the lung or other single sites. The diagnosis of PE was based on the demonstration of polycystic larval cestode lesions by radiological imaging (X-ray, US, CT scan) in patients born in tropical sylvatic areas of America where wild carnivores (canids, felids) and rodents (pacas and other species) were present. Serologic tests often, but not always, supported the diagnosis. Species identification of Ev or Eo were based on morphological characteristics of rostellar hooks from protoscoleces. The most common clinical presentation was abdominal; hard, round masses in or connected with the liver, hepatomegaly, increased abdominal size, pain, marked weight-loss and fever. Signs of portal hypertension were also present in 25% of cases, all of whom died of the disease or surgical complications following biliary drainage or partial hepatectomy. Ten percent were in asymptomatic persons. Albendazole treatment resulted in clinical improvement and disappearance or reduction of the size of lesions in some patients observed up to 24 months. The author believes that albendazole treatment should be tried before any other treatment is implemented. Human PE was reported from 11 countries, from Nicaragua to Argentina, 31 case were due to E. vogeli, three to E. oligarthrus (two orbital from Venezuela and Surinam and one cardiac from Brazil) and 38 were due to Echinococcus sp. (no rostellar hooks were available). PE reported from Nicaragua, Costa Rica, Chile, Argentina and Uruguay, countries outside the geographical range of the bush dog (only natural host of Ev) may have been due to Eo rather than to Ev. Several felids are known to serve as final host of Eo, and they are present in those areas. Epidemiological field studies of autochthonous human populations in tropical areas may contribute to early detection and make possible greater success in treatment of polycystic echinococcosis.

Adult↗