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Biomedical subjects

A Aquino

Publications and source records attributed to A Aquino.

At least 19 recordsLinked to original sources

Excited state properties of 7-hydroxy-4-methylcoumarin in the gas phase and in solution. A theoretical study.

TDDFT/B3LYP and RI-CC2 calculations with different basis sets have been performed for vertical and adiabatic excitations and emission properties of the lowest singlet states for the neutral (enol and keto), protonated and deprotonated forms of 7-hydroxy-4-methylcoumarin (7H4MC) in the gas phase and in solution. The effect of 7H4MC-solvent (water) interactions on the lowest excited and fluorescence states were computed using the Polarizable Continuum Method (PCM), 7H4MC-water clusters and a combination of both approaches. The calculations revealed that in aqueous solution the pi pi* energy is the lowest one for excitation and fluorescence transitions of all forms of 7H4MC studied. The calculated excitation and fluorescence energies in aqueous solution are in good agreement with experiment. It was found that, depending on the polarity of the medium, the solvent shifts vary, leading to a change in the character of the lowest excitation and fluorescence transition. The dipole-moment and electron-density changes of the excited states relative to the ground state correlate with the solvation effect on the singlet excited states and on transition energies, respectively. The calculations show that, in contrast to the ground state, the keto form has a lower energy in the pi pi* state as compared to enol, demonstrating from this point of view the energetic possibility of proton transfer from the enol to the keto form in the excited state.

Journal Article↗

The role of emergency thoracoscopy in the management of congenital cystic adenomatoid malformation of the lung associated with oesophageal atresia.

Congenital cystic adenomatoid malformation of the lung associated with oesophageal atresia is exceptional. The authors describe a case of a mixed type I - II congenital cystic adenomatoid malformation of the left lung associated with oesophageal atresia and tracheooesophageal fistula in a male infant. The interesting aspect of this case is not only the extremely rare association - only two reports in the literature - but the surgical choices. In fact, two weeks after surgical repair of the oesophageal atresia, the growth of the cystic volume of the congenital adenomatoid malformation made respiratory weaning very difficult, and it was therefore decided to solve the respiratory distress by opening the tensional cysts using a thoracoscopic access. The advantage of this treatment was that it decompressed the underlying healthy lung tissue and permitted the expansion of the normal lobar parenchyma. This is a palliative approach that allows the mandatory definitive resection of the affected lung lobe to be postponed until a later time.

Comorbidity↗

Preclinical studies on detection of circulating melanoma cells in patients: telomerase as a recognition marker of malignancy.

Preclinical studies based on a "simulation design", were performed with cultured melanoma cells prelabeled with 51Cr, added to normal blood and subjected to separation and recognition steps. Mononuclear cells (MNC) were isolated on ficollhypaque gradient, and melanoma cells were separated from lymphocytes using anti-CD45 immunomagnetic beads. Malignant cells were then recognized by measuring telomerase activity (TRAP and TRAP-ELISA assays). It was found that: (a)recovery of prelabeled cells present in MNC did not exceed 75%; (b) further recovery of prelabeled cells after separation from lymphocytes did not exceed 68%. Therefore, the overall recovery of prelabeled cells did not exceed 48%; (c) the entire procedure was able to reliably detect as few as 30 malignant cells added to normal blood, providing a telomerase signal significantly higher than that found in absence of melanoma cells. These results furnish the technical bases for developing a tumor detection assay in the blood of melanoma patients.

Biomarkers, Tumor↗

Bcl-2 has differing effects on the sensitivity of breast cancer cells depending on the antineoplastic drug used.

The aim of this paper was to evaluate the role of bcl-2 in the susceptibility of the MCF7 ADR human breast carcinoma line overexpressing the P-170 glycoprotein (P-170) to various drugs. The sensitivity to four multidrug resistance (MDR)-related drugs (doxorubicin (ADR), vincristine (VCR), vinblastine (VBL), actinomycin D (ACTD)) and three MDR-non-related drugs (cisplatin (DDP), bischloroethylnitrosourea (BCNU), 5-fluorouracil (5-FU)) was evaluated by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay in three bcl-2-overexpressing clones obtained from the MCF7 ADR line. We found that the bcl-2-overexpressing clones show increased resistance to DDP and BCNU, while no difference to 5-FU were observed between the control cells and bcl-2 transfectants. Surprisingly, bcl-2-overexpressing clones displayed an increased sensitivity compared with the control cells to the MDR-related drugs ADR, VCR, VBL and ACTD. Focusing on DDP and ADR, we found that the increased resistance of the bcl-2 transfectants to DDP was correlated to their ability to prevent apoptosis, while the enhanced sensitivity to ADR was associated with an increased ADR accumulation and a decreased ADR efflux. Moreover, while bcl-2 overexpression does not induce changes in P-170 glycoprotein expression, it did induce a reduction of the adenosine triphosphate (ATP) levels and basal protein kinase C (PKC) activity, both of which have a crucial role in the regulation of the MDR phenotype. In conclusion, the effect of bcl-2 on antineoplastic sensitivity observed in this study underscores the idea that bcl-2 may have distinct biological effects depending on the anticancer drug used.

Adenosine Triphosphate↗

Blue rubber bleb nevus syndrome and gastrointestinal haemorrhage: which treatment?

PURPOSE: To describe a paediatric case of "Blue Rubber Bleb Nevus Syndrome" (BRBNS) or Bean's syndrome, a rare systemic disorder characterised by cutaneous and gastrointestinal vascular malformations that often lead to overt life-threatening gastrointestinal bleeding or occult blood loss with severe anaemia and iron deficiency. CASE REPORT: A 6-year-old girl with multiple characteristic cutaneous vascular lesions was admitted for a massive rectal bleeding. A few months previously she was endoscopically treated for gastric angiomas which developed into melaena. Preoperative investigations revealed the recurrence of gastric lesions. At laparotomy, more than 25 angiomas of the GI tract were found. Multiple intestinal resections were carried out. RESULTS: No intraoperative or postoperative problems occurred and the girl is completely healthy without further bleeding after a follow-up period of three years. CONCLUSIONS: BRBNS belongs to the group of vascular venous malformations. Most of the time it occurs sporadically, but it can be inherited as an autosomal dominant trait. Recent analysis identified a locus on chromosome 9 responsible for venous malformations. BRBNS patients present typical skin lesions, with some lesions having a rubber-like nipple appearance; the number of skin and GI lesions and the severity of anaemia are correlated. Treatment is dependent on the extent of gut involvement and the severity of the clinical picture. In the absence of massive bleeding, a conservative treatment will be sufficient; otherwise resections are mandatory, but additional lesions may subsequently develop. Management with electrocautery or laser photocoagulation are usually not effective even if some reports recommend them. Pharmacological treatment is useless. Prognosis of BRBNS is unknown.

Child↗

A novel method for monitoring response to chemotherapy based on the detection of circulating cancer cells: a case report.

We describe a novel method for detecting micrometastasis in the blood stream of cancer patients based on RT-PCR amplification of tumor-associated carcinoembryonic antigen (CEA) mRNA. To increase sensitivity and specificity of RT-PCR, CEA transcript was selectively up-regulated in cancer cells by exposure of peripheral blood to non-toxic concentrations of staurosporine (ST). Thereafter, polyA(+) RNA was extracted from tumor cells captured by means of magnetic beads coated with a monoclonal antibody against a common human epithelial antigen. Finally, RNA was subjected to RT-PCR analysis of CEA transcript. Using this approach, we demonstrated an ST-mediated increase in CEA transcript in blood specimens collected from a patient with metastatic colon cancer before receiving treatment with 5-fluorouracil/leucovorin. After a few cycles of chemotherapy, CEA-positive tumor cells were no longer detected. Clinical follow-up of this patient indicated that treatment with chemotherapy induced a dramatic reduction in liver metastasis. Therefore, it can be hypothesized that lack of CEA transcript detection might be consistent with disappearance or at least marked reduction of circulating tumor cells.

Adenocarcinoma↗

The effects of an HIV-1 immunogen (Remune) on viral load, CD4 cell counts and HIV-specific immunity in a double-blind, randomized, adjuvant-controlled subset study in HIV infected subjects regardless of concomitant antiviral drugs.

OBJECTIVE: We examined the activity of an HIV-1 immunogen (Remune) on viral load, CD4 cells and HIV-1 specific immunity. METHODS: Plasma and peripheral blood mononuclear cells were obtained in a predefined random subset of subjects (n = 252) from a multicentre, double-blind, adjuvant-controlled phase III clinical endpoint study. RESULTS: The subjects treated with the HIV-1 immunogen had a significantly greater decline in viral load at multiple time points (P < 0.05), a trend towards increased CD4+ T cell counts and significantly enhanced HIV-1 specific immune responses as measured by HIV-1 lymphocyte proliferation (P < 0.001) compared to the adjuvant control group. Furthermore, in the HIV-1 immunogen treated group, enhanced HIV-1 specific lymphocyte proliferative immune responses were associated with decreased HIV-1 plasma RNA. CONCLUSION: These results suggest that, in a predefined, random subset of subjects, a beneficial effect of the HIV-1 immunogen was observed on viral load, CD4+ T cells, and HIV-specific immunity. These differences were observed in a background of multiple drug therapies. Ongoing trials are evaluating the effect of the combination of this HIV-1 specific, immune-based therapy with potent antiviral drug therapy on virological outcomes.

AIDS Vaccines↗

Clinical and hematological responses to hydroxyurea in Sicilian patients with Hb S/beta-thalassemia.

Although, several reports have detailed that hydroxyurea can ameliorate the clinical course of adult and pediatric patients with sickle cell anemia (Hb S or beta(S)), few clinical studies have been carried out in patients with beta(S)/beta-thalassemia. In a two-year clinical study, we evaluated the efficacy of hydroxyurea in a group of 22 adult Sicilian patients with beta(S)/beta-thalassemia with severe phenotypes. Among the 20 patients evaluated during 2 years of treatment, we observed a very good clinical response with a 93% reduction of the annual number of crises (median 7 versus 0.5 crises per year; P < 0.001) and of days in hospital (mean 22+/- 21.9 versus 1.2 +/- 2.3; P < 0.001), a significant increase in Hb F (7.5 +/- 5.3% versus 25.2 +/- 5.2%; P < 0.001) and in MCV (73.1 +/- 4.8 fL versus 96.4 +/- 7.2 fL; P < 0.001), and no significant modifications in Hb (9.6 +/- 1.3 g/dL versus 10.0 +/- 1.5 g/dL; P > 0.05) and in WBC (11.4 +/- 3.9 x 10(9)/L versus 10.2 +/- 3.9 x 10(9)/L; P > 0.05). Twelve patients had no crises from the first month of treatment; 16 patients showed a 2-3-fold increase over baseline in Hb F. During the study no severe complications and no important side effects of hydroxyurea were observed. Our data suggest that hydroxyurea efficacy in patients with beta(S)/beta-thalassemial may be greater than that described in patients with sickle cell disease. This pattern and durability of response will need to be confirmed in a larger, randomized, clinical trial.

Adult↗

Influence of Mycobacterium bovis bacillus Calmette Guérin on in vitro induction of CD1 molecules in human adherent mononuclear cells.

Nonpeptide antigens (including glycolipids of microbial origin) can be presented to T cells by CD1 molecules expressed on monocyte-derived dendritic cells. These HLA unrestricted responses appear to play a role in host immunity against Mycobacterium tuberculosis and other pathogenic bacteria. It is known that vaccination with Mycobacterium bovis bacillus Calmette-Guérin (BCG) has limited efficacy in many clinical settings, although the reasons for its inadequacy remain unclear. Here we have investigated the influence of BCG on the induction of CD1b on human monocytes by granulocyte-macrophage colony-stimulating factor (GM-CSF), which is believed to be the principal inducer of this antigen-presenting molecule. Although BCG alone led to a slight induction of CD1b expression, this agent reduced markedly the ability of GM-CSF to induce high levels of CD1b that were typically observed in uninfected cells. Inhibition of CD1b expression in BCG-infected monocytes was apparent at both the mRNA transcript and CD1b protein levels. Down-regulation of CD1b expression by BCG was mediated, at least in part, by one or more soluble factors and could not be reversed with high concentrations of GM-CSF or a variety of other cytokines. The present results suggest that BCG could diminish the efficiency of CD1-restricted T-cell responses against nonpeptide mycobacterial antigens by reducing CD1 expression on antigen-presenting cells. These findings have potential implications for understanding the nature of the immune response elicited by BCG in humans and suggest potential strategies that could be important for the development of better vaccines for the prevention of tuberculosis.

Antigen Presentation↗

In vitro generation of cytotoxic T lymphocytes against HLA-A2.1-restricted peptides derived from human thymidylate synthase.

5-Fluorouracil (5-FU) is a pyrimidine antimetabolite active against colorectal carcinoma and other malignancies of the digestive tract. Over-expression or mutation of thymidylate synthase (TS), the target enzyme of the 5-FU metabolite, 5-fluorodeoxyuridine monophosphate, is strictly correlated with cancer cell resistance to 5-FU. On this basis we investigated whether TS is a potential target for active specific immunotherapy of human colon carcinoma, which acquires resistance to 5-FU. Three TS-derived epitope peptides which fit defined amino acid consensus motifs for HLA-A2.1 binding were synthesized and investigated for their ability to induce human TS-specific cytotoxic T cell (CTL) responses in vitro. CTL lines specific for each peptide were established by stimulating peripheral blood mononuclear cells (PBMC) from an HLA-A2.1+ healthy donor with autologous dendritic cells loaded with TS peptide. Specific CTL lines showed HLA-A2.1-restricted cytotoxicity in vitro to HLA-A2.1+ target cells pulsed with the specific TS peptide and to HLA-class I matching colon carcinoma target cells over-expressing TS enzyme after exposure to 5-FU. Recognition by CTL lines suggests that these TS peptides may be potential candidates for use in a peptide-based vaccine against 5-FU resistant colon carcinoma.

Antimetabolites, Antineoplastic↗

Function of the windlass mechanism in excessively pronated feet.

The foot postures of 39 subjects were evaluated for excessive pronation by means of six static weightbearing and five nonweightbearing measurements, and two types of footprint indexes. Visual evidence of windlass function was recorded by video. Chi-square analysis revealed that excessive pronation does not affect the establishment of the windlass mechanism. The position of the forefoot relative to the rearfoot, subtalar joint axis position, and navicular drift/foot length ratio were significantly associated with dynamic windlass function. These results suggest that selected static measurements may have value in predicting some aspects of dynamic foot function during the propulsive phase of the gait cycle.

Adult↗

4-Hydroxynonenal-induced MEL cell differentiation involves PKC activity translocation.

4-Hydroxynonenal (HNE) is a highly reactive aldehyde, produced by cellular lipid peroxidation, able to inhibit proliferation and to induce differentiation in MEL cells at concentrations similar to those detected in several normal tissues. Inducer-mediated differentiation of murine erythroleukemia (MEL) cells is a multiple step process characterized by modulation of several genes as well as by a transient increase in the amount of membrane-associated protein kinase C (PKC) activity. Here we demonstrate that a rapid translocation of PKC activity from cytosol to the membranes occurs during the differentiation induced by HNE. When PKC is completely translocated by phorbol-12-myristate-13-acetate (TPA), the degree of HNE-induced MEL cells differentiation is highly decreased. However, if TPA is washed out from the culture medium before the exposition to the aldehyde, HNE gradually resumes its differentiative ability. The incubation of cells with a selective inhibitor of PKC activity, bisindolylmaleimide GF 109203X, partially prevents the HNE-induced differentiation in MEL cells. In conclusion, our results demonstrate that HNE-induced MEL cell differentiation is preceded by a rapid translocation of PKC activity, and that the inhibition of this phenomenon prevents the onset of terminal differentiation.

Aldehydes↗

Rate of infection and of reinfection by Echinococcus granulosus in rural dogs of the province of Rio Negro, Argentina.

Hydatidosis (cystic echinococcosis) constitutes a serious public health problem in the Province of Rio Negro, Argentina. In the present work it was intended to evaluate the prevalence of the canine echinococcosis in rural areas of the Province of Rio Negro and studied the reinfection rate in dogs after treatment with Praziquantel during the period 1980-1997. A total of 496 dogs were studied in 18 canine concentrations in order to establish the initial prevalence rate which was 42.3%. From 1980 onward dogs should have been systematically treated with anthelmintic every 2 months in rural areas and every 6 months in urban areas. We estimated that approximately 65% of dogs were treated. To determine the reinfection rate, 476 dogs (1984) and 598 dogs (1996) were studied after anthelmintic treatment during two sequential time periods (0-45; 46-90 days). In both cases treated animals were compared with untreated dogs. Prevalences were 3.5%, 6.7% and 21.3% in 1984 and 0.8%, 4.0% and 10.0% in 1996. For the purpose of surveillance a total number of 21,444 dogs were studied during 18 years. Prevalence of Echinococcus granulosus decreased significantly in the first year from 42.3% to 6.1%.

Animals↗

Bifid sternum: neonatal surgical treatment.

The sternal cleft is a rare congenital anomaly resulting from a fusion failure of the sternum, generally observed at birth and asymptomatic. Surgery is indicated to protect the heart and major vessels from trauma, to improve respiratory dynamics, and for aesthetic reasons. We observed 2 neonates for a superior and medial thoracic mass. The defect involved the upper two thirds of the sternum. The surgical operation for both patients consisted in the primary closure of the defect.

Aorta↗

Recurrent posttraumatic urethrovaginal fistula: a new application for ASTRA.

The authors describe the results of an application of the surgical technique called ASTRA (anterior sagittal transrectal approach) in the case of a 16-year-old girl with a posttraumatic urethrovaginal fistula. The young girl with a posttraumatic urethrovaginal fistula had recurrence after 4 surgical attempts at closure performed by the vaginal approach before it was definitively corrected with the ASTRA. Two years after the ASTRA operation the patient is well with a complete restitution of function confirmed by a voiding cystourethrogram and urodynamic and rectal manometric tests. The successful recovery confirmed that ASTRA may be an excellent method of treating the developmental or acquired anomalies of the perineal region.

Adolescent↗

Staurosporine increases carcinoembryonic antigen expression in a human colon cancer cell line.

Staurosporine (ST), a protein kinase C inhibitor, was found to produce antitumor effects against C22.20, a clonal subline derived from colon cancer HT-29 line, selected for low expression of carcinoembryonic antigen (CEA). However, as assessed by FACS analysis using propidium iodide, no apoptosis or cell cycle alteration was found on day 3 after treatment of C22.20 cells with ST (1-100nM). Exposure of cells to graded concentrations of the drug (i.e., from 1 to 25nM) resulted in a concentration-dependent increase in the percentage of CEA positive cells, as determined by flow cytometric analysis. However, when higher concentrations (i.e. 50nM - 100nM) of ST were used, the percentage of CEA positive cells declined compared to that detected in 25nM-treated tumor. Since these results were obtained in a clonal cell population, it is reasonable to hypothesize that induction rather than selection mechanism is involved in this phenomenon. The potential clinical interest of the present findings stems from the consideration that treatment with ST or its derivatives could improve sensitivity and efficacy of diagnostic and/or immunotherapeutic approaches based on CEA molecules.

Apoptosis↗

Drug-induced modulation of carcinoembryonic antigen (CEA) expression in neoplastic cells from a patient with rectal cancer.

Treatment with 5-fluorouracil (5-FU) or recombinant interferon-gamma (IFN), alone or in combination, was found to increase carcinoembryonic antigen (CEA) expression in several carcinoma cell lines. In this study we examined the in vitro effect of these agents on CEA expression of tumor cells, obtained from a patient operated for rectal cancer. The results showed that exposure of cancer cells to 5-FU or to IFN resulted in increased CEA levels in terms of percentage of CEA-positive cells and mean fluorescence values, as indicated by FACS analysis. However, drug combination did not induce CEA expression higher than that provided by single agents alone. Treatment with 5-FU or with IFN produced a reduction of the total number of viable cells. Moreover, Western blot analysis revealed that exposure of cancer cells to each drug was followed by a substantial increase of the total cellular CEA content. On the contrary, 5-FU in combination with IFN did not increase the expression of the antigen more than that obtained by single agents. Noteworthy, exposure of CEA-negative cells from adjacent normal rectal tissue to both agents alone or in combination, did not result in CEA induction. In conclusion, the present results suggest new approaches aimed at (a) increasing the sensitivity of diagnostic procedures based on detection of CEA-positive tumor cells; (b) facilitating the recognition of CEA-positive cancer cells by immune responses induced by anti-CEA peptide vaccines.

Adult↗