Cigarette smoking and hypertension influence nitric oxide release and plasma levels of adhesion molecules.

Progression of atherosclerosis is currently believed to involve interactions between leukocytes and vascular endothelium. Epidemiological risk factors for atherosclerosis such as hypertension and smoking are known to cause endothelial dysfunction, which is an early event in the atherosclerotic process; they also may be considered in the light of their effects on adhesion molecule expression and release. Little is known about the additive effect between these two risk factors on endothelial adhesion molecule expression and nitric oxide release.

Assessment of radical prostatectomy specimens and diagnostic reporting of pathological findings.

Proper examination of radical prostatectomy (RP) specimens from patients with prostate cancer (PCa) is critical for determining the need for adjuvant treatment and for predicting the outcome. The first step in the examination is represented by the assessment of the specimens. This includes proper fixation in formalin and whole-mount sectioning.

Urothelial papillary lesions. Development of a Bayesian Belief Network for diagnosis and grading.

The diagnosis and grading of urothelial papillary lesions are affected by uncertainties which arise from the fact that the knowledge of histopathology is expressed in descriptive linguistic terms, words and concepts. A Bayesian Belief Network (BBN) was used to reduce the problem of uncertainty in diagnostic clue assessment, while still considering the dependencies between elements in the reasoning sequence. A shallow network was designed and developed with an open-tree topology, consisting of a root node containing four diagnostic alternatives (papilloma, papillary carcinoma grade 1, papillary carcinoma grade 2 and papillary carcinoma grade 3) and eight first-level descendant nodes for the diagnostic features.

Novel G protein-coupled responses in leukocytes elicited by a chemotactic bacteriophage displaying a cell type-selective binding peptide.

Recently, we identified a neutrophil-binding phage displaying a novel peptide motif, GPNLTGRW. It was determined that this peptide, when displayed on bacteriophage (FGP phage), elicits a transient increase in cytosolic calcium. Here, we show that FGP phage stimulate neutrophil chemotaxis and induce a pertussis toxin-sensitive rise in cytosolic calcium in monocytes as well as in neutrophils.

[Barrett's esophagus: screening and prognosis].

The diagnostic criteria for Barrett's disease have changed very considerably during the last 10 years. Classically, the definition asked for columnar epithelium in the lower esophagus extending for at least 3 cm proximally. Now, the diagnosis rests on the finding of specialised intestinal metaplasia, i.

Increased concentrations of inflammatory mediators in unstable angina: correlation with serum troponin T.

Objective: To measure plasma interferon gamma, monocyte chemotactic protein-1 (MCP-1), and interleukin 6 and to assess their correlation with cardiac troponin T in unstable angina.

Design: Blood sampling in patients undergoing coronary arteriography for known or suspected ischaemic heart disease.

Patients: 76 patients divided in three groups: 29 with unstable angina (group 1), 28 with stable angina (group 2), and 19 without ischaemic heart disease and with angiographically normal coronary arteries (group 3).

CC chemokines and the receptors CCR3 and CCR5 are differentially expressed in the nonneoplastic leukocytic infiltrates of Hodgkin disease.

Lymph nodes with Hodgkin disease (HD) harbor few neoplastic cells in a marked leukocytic infiltrate. Since chemokines are likely to be involved in the recruitment of these leukocytes, the expression of potentially relevant chemokines and chemokine receptors were studied in lymph nodes from 24 patients with HD and in 5 control lymph nodes. The expression of regulated on activation, normal T cell expressed and secreted (RANTES), monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta was analyzed by in situ hybridization and that of CCR3 and CCR5 by immunohistochemistry and flow cytometry.

Nuclear changes in the normal-looking columnar epithelium adjacent to and distant from prostatic intraepithelial neoplasia and prostate cancer. Morphometric analysis in whole-mount sections.

Subtle morphological changes and molecular alterations have been reported in normal-appearing tissue in prostates with high-grade prostatic intraepithelial neoplasia (PIN) and prostate cancer (PCa). The severity and the distribution of these changes and alterations within the prostate gland have not been addressed in previous publications. The aim of this study was to investigate morphometrically the nuclear changes of the normal-looking columnar epithelium adjacent to and distant from high-grade PIN and PCa.

Effect of complete androgen blockade on pathologic stage and resection margin status of prostate cancer: progress pathology report of the Italian PROSIT study.

Objectives: To compare the pathologic stage and surgical margin status in patients undergoing either immediate radical prostatectomy or surgery preceded by 3 or 6 months of neoadjuvant hormonal treatment (NHT) in a prospective, randomized study.

Methods: Four hundred thirty-one men with prostate cancer were enrolled in the Italian randomized prospective PROSIT study. The whole-mount sectioning technique was used.

Identification of receptor ligands by screening phage-display peptide libraries ex vivo on microdissected kidney tubules.

A novel method to identify receptor ligands for defined renal tubular segments has been developed. Ex vivo screening of phage-display peptide libraries on isolated intact rat proximal convoluted tubules (PCT) and cortical collecting ducts (CCD) allowed the direct access of phage to the basolateral surface of tubular epithelial cells. Two distinct peptide motifs were selected for CCD and PCT, indicating differential expression of some membrane receptors on the basolateral surface of defined kidney tubule segments.

Assay of zofenopril and its active metabolite zofenoprilat by liquid chromatography coupled with tandem mass spectrometry.

Zofenopril is a pro-drug designed to undergo metabolic hydrolysis yielding the active free sulfhydryl compound zofenoprilat, which is an angiotensin converting enzyme (ACE) inhibitor, endowed also with a marked cardioprotective activity. A simple, highly sensitive specific LC-MS-MS method was developed for the determination of zofenopril and zofenoprilat in human plasma. In order to prevent oxidative degradation of zofenoprilat and its internal standard, their free sulfhydryl groups were protected by treatment with N-ethylmaleimide (NEM), which produced the succinimide derivatives.

Ras-related and MAPK signalling in neuronal plasticity and memory formation.

Ras-related guanosine triphosphatases (GTPases) couple receptor activity to a number of intracellular signalling events culminating in the control of cell morphology and gene transcription. In culture cells, the best-understood Ras-dependent signalling pathway involves the mitogen-activated protein kinase/extracellular-regulated kinase (MAPK/ERK) cascade. A growing body of evidence has recently been accumulating to suggest a crucial role of Ras and MAPK signalling in neuronal functions connected to synaptic plasticity.

[The role of lymph nodes in colon carcinoma].

Metastatic spread of colon cancer to intermediate lymph nodes is found, depending on tumor stage, in up to 44% of patients and to central lymph nodes in about 10%. The incidence of skip metastases is estimated not to exceed 5%. Tumorous involvement of pericolic lymph nodes occurs almost only within a 10 cm distance from the primary.

Prostate tissue and serum markers.

Serum prostate specific antigen (PSA) is elevated beyond the arbitrary cut-off point of 4.0 ng/ml in the majority of patients with prostate cancer (PCa). It may also be greater than 4.

Comparative bioavailability of two formulations containing atenolol and chlortalidone associated in a 4:1 fixed combination.

Atenolol (CAS 29122-68-7) and chlortalidone (CAS 77-36-1) are marketed associated in a 4:1 strength ratio (100/25 and 50/12.5 mg) for the treatment of hypertension. According to EU guidelines, the bioequivalence of one dosage strength can also cover additional strengths when the pharmacokinetics of a given drug is linearly related with the dose.

Morphological identification of the patterns of prostatic intraepithelial neoplasia and their importance.

High grade prostatic intraepithelial neoplasia (PIN) is the most likely precursor of prostatic carcinoma. PIN has a high predictive value as a marker for carcinoma, and its identification in biopsy specimens warrants repeat biopsy for concurrent or subsequent carcinoma. The only methods of detection are biopsy and transurethral resection; PIN does not greatly raise the concentration of serum prostate specific antigen (PSA) or its derivatives, does not induce a palpable mass, and cannot be detected by ultrasound.

Helicobacter pylori and gastric erosions. Results of a prevalence study in asymptomatic volunteers.

Background/aims: Helicobacter pylori is considered to be the primary cause of most forms of gastritis, but its role as a causative agent in gastric erosions is unclear. The aim of this study was to estimate the prevalence of gastric erosions and H. pylori infection in asymptomatic volunteers.

Amlodipine bioequivalence achieved with a very sensitive liquid chromatography tandem mass spectrometric bioassay.

Amlodipine (CAS 88150-42-9) is a 1,4-dihydropyridine derivative, one of the most widely used drugs for the management of essential hypertension. In developing manidipine (CAS 120092-68-4), a new antihypertensive drug, amlodipine was selected as the reference comparator drug in a Phase III double blind clinical trial. However, manidipine is formulated in hard gelatin capsules, whereas amlodipine is presented as a tablet.

Increased expression of peripheral benzodiazepine receptors on leukocytes in silent myocardial ischemia.

Objectives: The purpose of this study was to evaluate benzodiazepine receptor expression on leukocytes from patients with symptomatic or silent myocardial ischemia.

Background: Silent myocardial ischemia is frequently observed in patients with coronary artery disease. Pain can be effectively controlled by various endogenous mechanisms.

Morphometric index of adult renal cell carcinoma. Comparison with the Fuhrman grading system.

Various grading systems have been proposed for renal cell carcinoma (RCC), using nuclear, cytoplasmic, and architectural features. The available evidence suggests that nuclear grading is a better prognostic indicator than other types of grading schemes. Nuclear morphometry may still improve the correlation of the nuclear grading with survival, however, because observer consistency is lacking in the subjective grading of RCC.

Vascular endothelial growth factor expression and capillary architecture in high-grade PIN and prostate cancer in untreated and androgen-ablated patients.

Background: Recent studies have demonstrated that angiogenesis is a potent prognostic indicator for patients with prostate cancer (PCa) and have pointed out that the evaluation of vascular endothelial growth factor (VEGF) is useful in assessing the angiogenic phenotype in PCa. The aim of the study was to investigate immunohistochemically the expression of VEGF and its correlation with the pattern of capillary architecture in prostate cancer and high-grade prostatic intraepithelial neoplasia (PIN), in untreated and androgen-ablated patients.

Methods: Forty-five patients who underwent radical prostatectomy (RP) for localized prostate carcinoma were recruited for this study.

Changes in the normal-looking epithelium in prostates with PIN or cancer.

Background: In prostatic neoplasia, the time from tumour initiation and progression to invasive carcinoma often begins in men in the fourth and fifth decades of life and extends across decades. Until recently, the events initiating the process and the developments concomitant with the evolution towards invasive disease were largely unknown.

Methods: Quantitative and analytical methods are applied to provide insights into certain individual molecular events and their effects on the complex multiple feedback system of cellular metabolism and regulation in prostate neoplasia.

Bioequivalence of inhaled formoterol fumarate assessed from pharmacodynamic, safety and urinary pharmacokinetic data.

This paper deals with a crossover trial on healthy volunteers performed to obtain combined pharmacodynamic, safety and pharmacokinetic data in order to assess the bioequivalence of formoterol fumarate (CAS 43229-80-7) delivered by mono-dose dry powder inhalers, as test and reference. The trial was carried out on 24 Caucasian healthy male and female volunteers treated with 12 micrograms formoterol fumarate bihydrate capsules for inhalation route. Pharmacodynamics was evaluated through a challenge test with methacholine on the forced expiratory volume in 1 s (FEV1).