Search for genomic sequences of microbial agents in atherosclerotic plaques.

Atherosclerosis is a complex, multifactorial disease. Several studies have reported a possible association between infection with microbial agents and atherogenesis. Chlamydia pneumoniae (C. pneumoniae), Herpes Simplex Virus 1 (HSV1), Human Cytomegalovirus (HCMV), and Epstein Barr Virus (EBV) have been widely investigated for their possible role in atherosclerosis development, but the results obtained to date are contradictory. The aim of our study is to search DNA of the aforementioned infectious agents by means of Quantitative Real Time PCR in atherosclerotic plaques from carotid arteries obtained from 17 patients. Genomic sequences of C. pneumoniae, HSV1, HCMV were not found in any atherosclerotic lesion. Therefore, our results do not support the hypothesis of an association between these infectious agents and atherosclerosis. Conversely, three patients were found to be positive for EBV DNA, thus indicating that, at least in a limited number of patients, EBV could play a role in atherogenesis.

Clinical usefulness of serum pepsinogens I and II, gastrin-17 and anti-Helicobacterpylori antibodies in the management of dyspeptic patients in primary care.

BACKGROUND: Several tests have been proposed for evaluating dyspeptic symptoms and their relationship to the underlying gastric disease. Serum pepsinogens and gastrin-17 are known to be useful biomarkers for the detection of gastric pathologies. AIM: To evaluate the capability of screening dyspeptic patients in the primary care by analyses of serum pepsinogens I (sPGI) and II (sPGII), gastrin-17 (sG-17) and the IgG anti-Helicobacter pylori antibodies (IgG-Hp). PATIENTS AND METHODS: Three hundred and sixty-two consecutive patients with dyspeptic symptoms (208 females, mean age 50.6 +/- 16 years, range 18-88 years) referred by general practitioners for upper gastrointestinal endoscopy were enrolled. A blood sample was taken from each subject for IgG-Hp, sPGI, sPGII and sG-17 analyses. RESULTS: Two hundred and eighty-seven patients had a complete screening; of these, 132 resulted positive for Hp infection. Patients with atrophic chronic gastritis showed significantly lower serum pepsinogen I levels and sPGI/sPGII ratio than patients with non-atrophic chronic gastritis. Moreover, by calculating the values of sPGI by sG-17 and sG-17 by sPGII/sPGI, subjects with atrophic chronic gastritis could be distinguished from those with non-atrophic chronic gastritis and from those with normal mucosa, respectively. sG-17 levels were found to be a useful biomarker for the detection of antral atrophic gastritis, while the combination of sPGI, the sPGI/sPGII ratio and sG-17 was found effective in identifying corpus atrophy. CONCLUSION: A panel composed of PGI, PGII, G-17 and IgG-Hp could be used as a first approach in the 'test and scope' and/or 'test and treat' strategy in the primary care management of dyspeptic patients.

Defects of tyrosine289phenylalanine mutation on binding and functional properties of the human tachykinin NK2 receptor stably expressed in chinese hamster ovary cells.

A point mutation was made at position 289 in the transmembrane segment 7 of the human tachykinin NK2 receptor to yield a tyrosine/phenylalanine (Tyr/Phe) substitution. Chinese hamster ovary cells stably transfected with the wild-type or Tyr289Phe mutant NK2 receptor both bound neurokinin A (NKA) and the synthetic NK2 receptor-selective agonists, GR 64349 and [betaAla8]NKA(4-10), with high and even affinities. Neurokinin B (NKB) and substance P (SP) also displayed sizeable binding affinities, albeit with lower affinity as compared to NKA. In a functional assay (production of inositol-1,4,5-trisphosphate, IP3), NKA, GR 64349, and [betaAla8]INKA(4-10) stimulated IP3 accumulation via the wild-type and mutant receptors with similar potencies. On the other hand, NKB and SP exhibited a dramatic reduction in their agonist efficacies at the mutant receptor, NKB acting as a partial agonist (maximum effect = 50% of the response to NKA) and SP being totally inactive. The results obtained with phenoxybenzamine inactivation experiments indicated that a large and similar receptor reserve existed for both the wild-type and the mutant receptor. SP, which displayed sizeable binding affinity for the mutant receptor but did not stimulate IP3 accumulation, antagonized the agonist effect of NKA. The antagonist action of SP at the mutant NK2 receptor cannot be ascribed to receptor internalization. The Tyr/Phe replacement at position 289 markedly reduced the binding affinity and antagonist potency of the non-peptide ligand, SR 48968, without affecting the binding affinity and antagonist potency of the bicyclic peptide antagonist MEN 11420. The results indicate that the hydroxyl radical function of Tyr289 in transmembrane segment 7 of the human NK2 receptor is, directly or indirectly, involved in stimulus transduction when the NK2 receptor is occupied by NKB or SP, but not when using NKA or NK2 receptor-selective agonists.

Pancreatic A- and D-cell response to arginine during acute alloxan-induced intra-islet insulinopenia.

This study was performed to investigate the role of pancreatic B-cell function on glucagon and somatostatin response to arginine. Isolated perfused rat pancreas was used for the experiment. Acute B-cell destruction was induced in vitro by 0.56 mM alloxan infused directly into the vascular system of the perfused pancreas. This resulted in a fall in basal insulin release and in a complete absence of hormone response to 20 mM arginine. Glucagon and somatostatin release during metabolic stimulus was superimposable on that observed in the control experiments (no alloxan infusion). We conclude that a normal B-cell function is not required for glucagon and somatostatin response to arginine.

[Choice of anesthesiological technic in ambulatory practice by means of psychodiagnostic tests]. / Scelta mediante tests psicodiagnostici della tecnica anestesiologica nella pratica ambulatoriale.

Psychodiagnostic tests have been used in a study on patients undergoing general anaesthesia for minor surgery, the purpose being to evaluate patient recovery and autonomy prior to discharge. The patients considered were submitted prior to operation to the Peg board test, tre Trieger test and the Writing test to obtain standard reference values. These tests were repeated every 10-15 minutes from the end of operation as soon as patients recovered consciousness and were able to cooperate. The comparative study showed that patients who had been anesthetized with Ethrane recovered more rapidly, followed by those treated with Fluothane, Propanidide and Althesin.

[Psychological problems in intensive care. I. The Resuscitation Center]. / Problemi psicologici in terapia intensiva. Parte prima. II Centro di Rianimazione.

Intensive therapy units are defined and their operation is explained for the benefit of the non-specialist, so as to clarify the background of the psychological situations in question. An investigation was made of the factors that may interfere with the smooth running of an intensive therapy department, where work is often done under emergency conditions. Interviews between psychologists, and physicians, paramedical staff and patients were chosen as a means of responding to this need. Open interviews were related to the length of hospital stay, patient age and sex, the clinical pictures of subjects admitted to the Resuscitation Centre, and another group admitted to the Coronary Unit. The results were examined with reference to: examinations during hospitalisation, things remembered about the period of admission, dominant thoughts during the acute stage, attitude towards the care received, and changes proposed by the patient. From an examination of these features, assessments are made with regard to the relations and interaction between each component, particularly between doctor and patient in coma, and patient and nursing staff and resuscitation centre and other departments. Particular stress is laid on the delicacy of the relationships with relatives and persons admitted to RC. Some technical advice is offered as the conclusion to the examination of the RC forming the first part of the research.

[Ocular electrophysiologic study of patients with a family history of diabetes]. / Etude électrophysiologique oculaire chez des malades avec antécédent familial diabétique.

The electrofunctional alterations in a group of non diabetic patients with diabetic familiarity are considered. A high percentage of electrofunctional abnormalities was found in these patients as compared with fundus eye changes and blood glucose metabolic imbalances.

Therapy for intercurrent respiratory infections in COLD patients: report on 200 patients.

Over the last 2 years we have applied a therapeutic regimen with simultaneous use of cephalexin and bromhexine in therapy for infective exacerbations of COLD patients. The results obtained are positive. Bacteriologic features, the modification of sputum and, where possible, behavior of hematologic parameters and blood gases were checked. This pharmacologic combination appears to be useful in pneumology, as it yields very good results in obstructive chronic bronchitis in a bacterial relapsing phase and with alveolar hypoventilation linked to massive presence of endoluminal mucus. With the exception of two patients, in whom nausea and gastric pyrosis were observed, we observed no toxic or side effects of any kind, not even in subjects treated for a long time.

Pharmacokinetics of theophylline and the H2-antagonist drugs cimetidine and ranitidine.

This study tested the hypothesis that cimetidine and ranitidine, the new H2-antagonist, may influence the pharmacokinetics of theophylline administered i.v. at two different doses (3.4 and 6.5 mg/kg body wt.). Twenty hospitalized patients with chronic obstructive lung disease (COLD) and peptic ulcer were administered cimetidine or ranitidine orally for 8 days at the routine doses of 2 X 400 mg/day and 2 X 150 mg/day, respectively. Blood samples were collected over a 10-h period before and after H2-antagonist therapy. Cimetidine significantly reduced theophylline clearance, but increased its half-life and the area under the curve (AUC) (p less than 0.001). Ranitidine, on the contrary, did not show any interaction with these pharmacokinetic parameters. Neither of the H2-blocking agents modified the volume of distribution. Furthermore, the delay in theophylline elimination due to cimetidine was more evident at the higher dose of the xanthic drug; this effect induced remarkable changes in plasma theophylline concentrations. Consequently, pharmacokinetic interaction between cimetidine and theophylline may produce serious clinical problems in the management of patients treated with both drugs concurrently, problems which do not arise with ranitidine.

Effects of beta non-selective and beta 1 selective adrenergic blocking agents on glucagon secretion from isolated perfused rat pancreas.

To characterize beta-receptors which affect pancreatic A-cell activity, the effects of propranolol (beta non-selective blockade) and metoprolol (beta 1 selective blockade) were evaluated on epinephrine modulated insulin (IRI) and glucagon (IRG) release both in basal state and during metabolic stimulus (arginine 20 mM). The isolated perfused rat pancreas model with the exclusion of stomach and duodenum was used. Epinephrine infusion (at 10(-7) M) caused a prompt and sustained increase in basal IRG secretion and significantly potentiated glucagon release in response to metabolic stimulus. Insulin secretion was markedly suppressed by epinephrine both in basal conditions and during metabolic stimulus. Propranolol (at 10(-7) M) and metoprolol (at 10(-7) M) infusion clearly and similarly counteracted epinephrine stimulatory effects on IRG secretion but failed to elicit any significant effect on the epinephrine inhibited IRI release either in basal state or during the metabolic stimulus. These results suggest that, at least in the rat, the adrenergic stimulation of IRG release is mediated through a beta 1 receptor.

Evidence for a prostaglandin-mediated bone resorptive mechanism in subjects with fasting hypercalciuria.

This study was performed to assess whether treatment with prostaglandin synthesis inhibitors decreases calcium excretion in patients with idiopathic hypercalciuria. Nineteen hypercalciuric (12 with fasting hypercalciuria (FH), 7 with nonfasting hypercalciuria (NFH) and 8 control non-hypercalciuric stone formers were treated with sodium diclofenac, 50 mg t.i.d. for 2 weeks. After a washout phase, 7 FH patients received 200 mg/day of sulindac (a nonsteroidal antiinflammatory agent (NSAID) inactive on renal prostaglandin synthetase) for 14 more days. Diclofenac reduced urine calcium excretion in subjects with idiopathic hypercalciuria with either normal or elevated fasting urinary calcium (from 387 +/- 26 to 240 +/- 23 mg/day, P less than 0.001; and from 370 +/- 39 to 246 +/- 40 mg/day, P less than 0.05, respectively), whereas it was ineffective in normocalciuric stone formers. Similar antihypercalciuric effectiveness was exerted by sulindac in the seven FH patients. The antihypercalciuric action exerted by diclofenac in subjects with FH was associated with a significant increment in serum PTH (48 +/- 4 vs, 70 +/- 9 pmol/liter, P less than 0.05), whereas in NFH subjects, the antihypercalciuric effect of diclofenac on NFH was not associated with a change in parathyroid activity. Since the major effect of NSAIDs is to decrease prostaglandin synthesis, these data suggest that prostaglandins may play a pathogenetic role in idiopathic hypercalciuria. Furthermore, they suggest that PTH is suppressed in patients with FH, possibly due to stimulation of prostaglandin-mediated bone resorption process.

Production of recombinant human GM-CSF-EPO hybrid proteins: in vitro biological characterization.

Selective lineage differentiation depends upon the combined action of several colony-stimulating factors. Here we describe 3 human granulocyte-macrophage colony-stimulating factor-erythropoietin (GM-CSF-EPO) hybrid proteins generated by recombination of the relevant cDNAs. The expression vector containing the murine cytomegalovirus (mCMV) promoter and dihydrofolate reductase (DHFR) gene was used for the expression of the hybrid genes in Chinese hamster ovary (CHO) cells. Purified hybrid proteins from CHO transfectant cultures induced proliferation of both EPO and GM-CSF dependent cell lines. The clonogenic test, performed on purified human hematopoietic precursor cells, indicates that the hybrid proteins are more efficient at inducing erythroid differentiation compared with the equimolar mixture of GM-CSF and EPO.