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Biomedical subjects

A Coppola

Publications and source records attributed to A Coppola.

At least 19 recordsLinked to original sources
PubMed1999

Effect of Helicobacter pylori infection and its eradication on cell proliferation, DNA status, and oncogene expression in patients with chronic gastritis.

BACKGROUND: Helicobacter pylori, the main cause of chronic gastritis, is a class I gastric carcinogen. Chronic gastritis progresses to cancer through atrophy, metaplasia, and dysplasia. Precancerous phenotypic expression is generally associated with acquired genomic instability. AIM: To evaluate the effect of H pylori infection and its eradication on gastric histology, cell proliferation, DNA status, and oncogene expression. METHODS/SUBJECTS: Morphometric and immunohistochemical techniques were used to examine gastric mucosal biopsy specimens from eight controls, 10 patients with H pylori negative chronic gastritis, 53 with H pylori positive chronic gastritis, and 11 with gastric cancer. RESULTS: All patients with chronic gastritis were in a hyperproliferative state related to mucosal inflammation, regardless of H pylori infection. Atrophy was present in three of 10 patients with H pylori negative chronic gastritis and in 26 of 53 with H pylori positive chronic gastritis, associated in 18 with intestinal metaplasia. DNA content was abnormal in only 11 patients with atrophy and H pylori infection; eight of these also had c-Myc expression, associated in six cases with p53 expression. Fifty three patients with H pylori positive chronic gastritis were monitored for 12 months after antibiotic treatment: three dropped out; infection was eradicated in 45, in whom cell proliferation decreased in parallel with the reduction in gastritis activity; atrophy previously detected in 21/45 disappeared in five, regressed from moderate to mild in nine, and remained unchanged in seven; complete metaplasia disappeared in 4/14, and markers of genomic instability disappeared where previously present. In the five patients in whom H pylori persisted, atrophy, metaplasia, dysplasia, and markers of genomic instability remained unchanged. CONCLUSIONS: Chronic H pylori infection seems to be responsible for genomic instability in a subset of cases of H pylori positive chronic atrophic gastritis; eradication of H pylori infection can reverse inflammation and the related atrophy, metaplasia, and genomic instability.

Adult↗
PubMed1998

Efficacy of a new topical gel-spray formulation of ketoprofen lysine salt in the rat: percutaneous permeation in vitro and in vivo and pharmacological activity.

The aim of this study was to evaluate the percutaneous permeation of a new topical Gel-Spray formulation, containing 15% of ketoprofen lysine salt (KLS), both in vitro, using the Franz-type diffusion cells and in vivo, by evaluating urinary recovery after topical administration and to correlate the absorption data with KLS pharmacological activity in the rat. Concentrations of ketoprofen free acid (KFA) were determined by HPLC in the receptor compartment (in vitro), or in urine (in vivo). The permeation of ketoprofen evaluated in vitro after the application of KLS Gel-Spray was higher than that observed with the marketed formulation Profénid gel (containing KFA at 2.5%). The same evidence was found in vivo, except when the ratio between the administered dose and the area treated was higher than 1 mg cm-2. Thus, the difference between the two formulations seems to be the resultant of two opposing components: a positive gradient of concentration that favours the absorption of ketoprofen from KLS Gel-Spray and the presence of the enhancer ethanol that could favour the efficacy of Profénid gel. Under our conditions the former prevailed. As for the efficacy, evaluated in the carrageenan-induced oedema and hyperalgesia model, KLS Gel-Spray confirmed the data obtained for in vivo absorption, being more efficient than the reference standard Profénid gel. The observed inhibitory effects were due only to dermal absorption, oral absorption was excluded by an Elizabethan collar applied around the neck of the rat. In these experimental conditions, no significant damage of the rat stomach mucosa was observed. These results indicate that KLS Gel-Spray, due to its high KLS concentration, allows a very high efficiency in delivering ketoprofen to the inflamed area using a minimal amount of formulation, even in the absence of permeation enhancers.

Animals↗
PubMed1998

Double-stranded DNA can be translocated across a planar membrane containing purified mitochondrial porin.

The transport of genetic material across biomembranes is a process of great relevance for several fields of study. However, much remains to be learned about the mechanisms underlying transport, one of which implies the involvement of proteic DNA-conducting pores. Entry of genetic material into mitochondria has been observed under both physiological and pathological conditions. We report here that double-stranded DNA can move through a planar bilayer membrane containing isolated mitochondrial porin (voltage-dependent anion channel). The transport is driven by the applied electrical field, and the presence of DNA is associated with a decrease of current conduction by the pores. The passage of DNA does not take place if the bilayer has not been doped with any protein or in the presence of both reconstituted porin and anti-porin antibody. Translocation does not occur if the bilayer contains Shigella sonnei maltoporin, gramicidin A channels, or a 30 pS anion-selective channel plus other proteins. These results show that mitochondrial porin is capable of mediating the transport of genetic material, revealing a new property of this molecule and further confirming the idea that DNA can move through proteic pores.

Biological Transport↗
PubMed1998

Antiphospholipid syndrome, adrenal failure, dilated cardiomyopathy and chronic hepatitis: an unusual manifestation of multiorgan autoimmune injury?

The antiphospholipid syndrome is characterized by clinical evidence of arterial or venous thrombosis, thrombocytopaenia, recurrent fetal loss and repeated positivity of antiphospholipid autoantibodies. The association of antiphospholipid syndrome with the development of adrenal failure has been reported in more than 40 patients in the last 20 years, mostly due to bilateral cortical haemorrhage or thrombosis of adrenal vessels. The presence of antibodies against adrenal cortex was never documented in these patients. Here we report a case of recurrent thrombophlebitis, acute adrenal failure, and chronic hepatitis occurring in a young man found to have antiphospholipid antibodies and lupus anticoagulant. Autoantibodies against adrenal cortex were detected and abdominal ultrasonography showed morphologically normal adrenals. Mild thrombocytopaenia, Coomb's positive anaemia, increase in alanine- and aspartate-aminotransferases and increase in urinary protein excretion were found. Autoantibodies against liver/kidney microsomes were positive and liver biopsy was compatible with autoimmune hepatitis. The patient was treated with cortisone acetate, fludrocortisone and warfarin. Dilated cardiomyopathy was revealed one year later and coronarography did not document any occlusive coronary disease. Three years later, titres of autoantibodies, including those directed towards the adrenal cortex, were increased and others, previously absent, were detected. Nevertheless, the patient's clinical conditions seemed unchanged. At this time, an abdominal CT scan showed adrenal dysmorphisms with bilateral annular calcifications and central hypodensities suggesting previous bilateral adrenal haematomas. The hypercoagulable state that occurs in antiphospholipid syndrome can induce a localized inflammatory response generated by tissue injury, with a consequent release of intracellular antigens and antibodies production. Consequently, tissue-specific autoantibodies positivity may persist until the cells involved in antigen production are completely destroyed.

Adrenal Insufficiency↗
PubMed1998

[Prolactinoma in the male. Physiopathological, clinical, and therapeutic features].

Among the various endocrine forms impotence associated with hyperprolactinaemia is discussed in this paper. A more relevant clinical picture is particularly due to prolactinoma. A marked reduction or suppression of libido and sexual power are mostly present; sometimes an altered spermatogenesis with oligospermia and infertility may be found; on the contrary galactorrhea and gynaecomastia are less frequent. Symptoms and signs of hypopituitarism or extrasellar growth may be found too. The main physiopathologic aspects as well as biochemical and instrumental diagnostic evaluation methods of prolactinoma in men are examined. The treatment may be pharmacological, surgical or radiant: indications and efficacy of each one are reported. A guide-line in case of macro- or microprolactinoma is explained too. With regard to pharmacological treatment, dopaminergic agonists have been available for more than twenty years and there is a wide experience with bromocriptine. Among the latest dopaminergic agonists, cabergoline is very interesting because it is effective, selective and long-term active; its pharmacological features are mentioned. At last, personal experience in three men, one suffering from micro- and two from macroprolactinoma recently treated with cabergoline is reported. Clinical aspects and hormonal and instrumental data before treatment are presented. Clinical and hormonal evaluations have been made after 2, 3 and 6 months of therapy and TAC control after the sixth month. The results allowed to verify the effectiveness of the drug.

Cabergoline↗
PubMed1997

DNA translocation across planar bilayers containing Bacillus subtilis ion channels.

The mechanisms by which genetic material crosses prokaryotic membranes are incompletely understood. We have developed a new methodology to study the translocation of genetic material via pores in a reconstituted system, using techniques from electrophysiology and molecular biology. We report here that planar bilayer membranes become permeable to double-stranded DNA (kilobase range) if Bacillus subtilis membrane vesicles containing high conductance channels have been fused into them. The translocation is an electrophoretic process, since it does not occur if a transmembrane electrical field opposing the movement of DNA, a polyanion, is applied. It is not an aspecific permeation through the phospholipid bilayer, since it does not take place if no proteins have been incorporated into the membrane. The transport is also not due simply to the presence of polypeptides in the membrane, since it does not occur if the latter contains gramicidin A or a eukaryotic, multi-protein vesicle fraction exhibiting 30-picosiemens anion-selective channel activity. The presence of DNA alters the behavior of the bacterial channels, indicating that it interacts with the pores and may travel through their lumen. These results support the idea that DNA translocation may take place through proteic pores and suggest that some of the high conductance bacterial channels observed in electrophysiological experiments may be constituents of the DNA translocating machinery in these organisms.

Aequorin↗
PubMed1997

The clinical course of cervical carcinoma in situ diagnosed during pregnancy.

OBJECTIVE: The objective was to determine the frequency with which regression or progression of disease without treatment occurred in women diagnosed with squamous cell cervical carcinoma in situ (CIS) during pregnancy. METHODS: . A retrospective chart review of all women evaluated at the University of Iowa Colposcopy Clinic diagnosed with CIS during pregnancy from 1987 through 1992 was used. Thirty-four women were evaluated during pregnancy, of which 26 also had postpartum evaluation. All pathology reports of initial cytology and biopsies, as well as colposcopic impressions, were reviewed and compared to the same evaluations postpartum. RESULTS: Of the 26 women evaluated both antepartum and postpartum, only 1 was treated (cone biopsy) during pregnancy. She had disease suspicious for microinvasion. She was disease free postpartum. Of the remaining 25, 20 (80%) had persistent disease, 2 (8%) had either missed disease or progressive disease postpartum, and 3 (12%) resolved without treatment at postpartum evaluation. No statistical significance was found between route of delivery and persistence (P = 0.34). No statistical significance was found between smoking and persistence of disease (P = 1.0). In 46% of women the initial cytology was CIN I or II, and the initial colposcopic impression was found to underestimate the severity of the disease in 35% of cases. Two women were found to have invasive disease postpartum. CONCLUSIONS: There is a high persistence rate of CIS complicating pregnancy. Given the relatively high rate of underestimation of disease severity by both cytology and colposcopic impression, the use of routine biopsy at the time of colposcopy is recommended. Invasive disease may be encountered on postpartum evaluation.

Adult↗
PubMed1997

In vivo gene transfer: prevention of neointima formation by inhibition of mitogen-activated protein kinase kinase.

BACKGROUND: The mitogen-activated protein kinase kinase (MAPKK) is a protein downstream ras which is rapidly activated in cells stimulated with various extracellular signals. These proteins are believed to play a pivotal role in integrating and transmitting transmembrane signals required for cell growth. METHODS AND RESULTS: To study the effect of inhibition of MAPKK on smooth muscle cell (SMC) proliferation in vivo after vascular injury, we performed experimental balloon angioplasty using the standard Clowes technique in male Wistar rats 14-weeks old. The animals did not receive any treatment after vascular injury (N = 6) or were randomly assigned to receive, after balloon injury, a 30% (w/v) pluronic gel solution applied to the injured carotid artery, containing respectively: 1) no plasmid DNA (n = 10); 2) RSV-lacZ (encoding the beta-galactosidase gene) as control gene without effects on SMC proliferation (n = 10); 3) Tg-CAT (encoding cloramphenicol acetyl-transferase gene under the control of thyreoglobulin promoter) as an additional control gene without effects on SMC proliferation (n = 7): 4) a negative mutant of Mitogen-Activated Protein Kinase Kinase (MAPKK-) (n = 13). Fourteen days after vascular injury, carotid arteries were removed and cross sections were cut and stained with hematoxylin/eosin. Morphometric analysis demonstrated, in the MAPKK- treated rats, a significant reduction of both neointima (0.096+/-.018 mm2 vs. 0.184+/-0.019 mm2, p < 0.01) and neointima/media ratio (0.603+/-0.103 vs. 1.471+/-0.161, p < 0.01) compared to control DNA. CONCLUSIONS: The inhibition of MAPKK, by a dominant inhibitor mutant gene, prevents the SMC proliferation after vascular injury in vivo.

Animals↗
PubMed1997

[Endocrine diseases and male infertility].

Male infertility is secretory or excretory. The excretory form lies outside the endocrinologist's evaluation. As regards the secretory form, infertility practically identifies itself with hypogonadisms, both primitive, congenital or acquired, that spring from testicular alterations, and secondary to that result from gonadotropic deficiency however derived. The various diseases and the large number of events responsible for primitive or secondary male hypogonadism and so cause of infertility, are minutely examined. Peripheral hypogonadism forms are mentioned in brief too. During diagnostic evaluation, anamnesis and objective examination are the first step. Afterwards hormonal basal dosages supply useful information in case of severe oligospermia or azoospermia. Particularly FSH plasma dosage values the tubular function and this hormone is the most significant clinical and prognostic parameter. LH plasma dosage is less useful. FSH and LH levels allow us to distinguish hypergonadotropic hypogonadism from the hypogonadotropic type. Testosterone dosage is also important. Prolactin measurement is useful too and likewise, in particular cases, other hormone measures. Dynamic tests are also mentioned. As a therapeutic guideline, treatment with androgens is exclusively substitutive in primitive hypogonadism, however of no avail on spermatogenesis; in cases of secondary hypogonadism, gonadotropins give satisfactory results; pulsatile Gn-RH use is not easy anyway; clomifen and tamoxifen don't seem of particular advantage; in hyperprolactinemia, dopaminergic drugs improve seminal parameters.

Endocrine System Diseases↗
PubMed1996

Effect of age and relation to mortality on serial changes of vasoactive intestinal peptide in acute myocardial infarction.

Plasma levels of vasoactive intestinal peptide increase early after acute myocardial infarction (AMI) and are significantly higher during the first 2 weeks of AMI in survivors and younger patients (<60 years) than in those who died and in older (>60 years) patients. Data suggest that vasoactive intestinal peptide is involved in neuroendocrine activation occurring in AMI and could be regarded as a marker of the course of AMI.

Adult↗
PubMed1996

[Neuroendocrine activation in acute myocardial infarction: state of the art and preliminary results on intestinal vasoactive peptide].

Acute myocardial infarction (AMI) is known to be associated with a complex neuroendocrine activation, especially concerning sympathetic and renin-angiotensin systems, cortisol, atrial natriuretic peptide and endothelin. Results of our study show that the vasoactive intestinal peptide (VIP), also, is early involved in the neuroendocrine activation occurring in AMI. Plasma concentration of VIP, significantly increased in AMI patients within 6 hours after the onset of chest pain, soon decreased and remained below than normal along the first week. At the 14th day of the AMI, plasma levels of VIP returned into the normal range. A significant increase of VIP plasma concentration is detectable in the first hours of AMI in survived as compared with died patients. The phenomenon seems to be a suitable process to provide an endogenous support to the ischemic heart and to counteract the negative effects of other neuroendocrine activated factors.

Adult↗
PubMed1995

Comparison of rest-redistribution thallium-201 imaging and reinjection after stress-redistribution for the assessment of myocardial viability in patients with left ventricular dysfunction secondary to coronary artery disease.

Thallium (Tl)-201 reinjection after stress-redistribution (RI) imaging has been proven to accurately identify ischemic and viable myocardium. Quantitative Tl-201 analysis after stress has also shown viable myocardium in most mild to moderate (51% to 85% of normal uptake) irreversible Tl-201 defects. However, if the main clinical question is whether a region is viable, and not whether there is inducible ischemia, a resting protocol may be more appropriate. The aim of this study was to determine whether rest-redistribution (RD) quantitative Tl-201 single-photon emission tomographic imaging provides the same information on viable myocardium as Tl-201 RI. Thus, 15 patients (mean age 58 +/- 9 years) with chronic coronary artery disease and left ventricular dysfunction (ejection fraction 35 +/- 8%) were studied by both RI and RD Tl-201 single-photon emission tomography. Regional Tl-201 uptake was assessed quantitatively using a 16-segment model. When Tl-201 images were classified as normal/reversible (viable) or irreversible (nonviable), RI showed viable myocardium in 145 of 240 myocardial regions (60%), whereas RD showed it in 103 of 240 myocardial regions (43%). The 2 imaging protocols provided concordant information in 176 of 240 myocardial regions (73%). Among the 64 (27%) discordant regions, 53 (22%) were viable by RI and nonviable by RD, whereas 11 (5%) were viable by RD and nonviable by RI (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

A community-based cervical screening program in a remote Aboriginal community in the Northern Territory.

We established a culturally appropriate, community-based women's health service in Yuendumu, Northern Territory, to improve women's health and to remedy the low rate of cervical screening. During the 16 months of the program 419 cervical smears were taken, increasing coverage of the women eligible from 51 to 78 per cent. Acceptance of the program was excellent, with only 2 per cent of the women approached refusing to have a smear. Over 70 per cent of the Pap smears were done by the nursing staff in the clinic; quality control was good, with 9 per cent of smears reported as having no endocervical cells. Sixty-four per cent of screened women had normal smears and 0.9 per cent showed evidence of cervical intraepithelial neoplasia (CIN). Three women were referred for treatment of CIN, two for CIN I and one for CIN III. The program illustrates how a combination of community involvement, staff stability, teamwork, and cross cultural understanding can achieve a comprehensive and successful cervical screening service in a remote Aboriginal community.

Adolescent↗
PubMed1995

[The peak of creatine phosphokinase level in the acute phase of myocardial infarction in patients with and without ischemic precedents].

Two hundred and one patients admitted to Coronary Care Unit with documented acute myocardial infarction, whose chest pain had occurred within 12 hours of hospital admission non thrombolised, were studied. The peak of creatine kinase (CK) was examined and compared between patients without previous manifestations of myocardial ischemia (group A, 106 patients) and patients with/history angina pector or healed myocardial infarction (group B, 95 patients). The mean peak creatine kinase level in the negative history group was higher (2261 +/- 226 U/L vs 1779 +/- 97 U/L p < 0.001), especially in patients aged less than 65. No significant difference was observed in patients aged more than 64 of the two groups. Patients with a positive history presented more frequently ischemic complications (p < 0.05) while the frequency of hemodynamic disturbances and arrhythmias was not significantly different. Total mortality was similar in the two groups (22.6% vs 21%) and more frequently occurred in older patients with congestive heart failure. The authors form the hypothesis that the higher mean peak creatine level in patients without previous myocardial ischemia is the result of absence of coronary collateral circulation. The presence of collateral vessels permits less extensive myocardial infarction but it does not change the prognosis.

Aged↗