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Biomedical subjects

M Orlandi

Publications and source records attributed to M Orlandi.

90 records · Page 5Linked to original sources

[CK MB versus total CK in the estimation of myocardial necrosis. Comparative kinetic analysis and evaluation of an immunological method].

It has been suggested that the adoption of a relatively specific marker of the myocardial cell, such as creatine kinase MB isoenzyme, can yield improved accuracy in estimating infarct size by serial serum sampling and compartmental analysis. Nevertheless, current methods for the evaluation of isoenzyme activity are cumbersome and unsuitable for clinical use. We have therefore employed a new test for the rapid determination of CK MB activity, based on the immunological inhibition of M subunities. In 19 patients not submitted either to intramuscular injection or to repeated defibrillations, a good correlation was found between indexes of necrosis based on MB and total CK determination (r = 0.94), with the cumulative MB release amounting to 16 +/- 4% of total CK. Significant differences were observed in 3 patients submitted to external cardiac massage (MB = 9 +/- 1% of total CK) thus suggesting a considerable extracardiac source of total CK due to the trauma of the skeletal muscle. The comparative kinetic analysis shows substantial differences between the two isoenzymes, not only concerning the greater disappearance rate of CK MB but, more significantly, related to a faster release of this isoenzyme from the myocardium, which has not been previously reported. The good correlations found between maximal appearance rate and cumulative enzyme release (r = 0.86) suggest that the former may represent an index of the rate of degradation of cellular membranes. Practical implications of these data are discussed.

Creatine Kinase↗

["Pericarditis epistenocardica" as as a marker of extensive myocardial infarction. Clinical, electrocardiographic and enzymatic study (author's transl)].

Pericarditis may complicate the early phase of myocardial infarction (MI). It occurs when necrosis involves the epicardial surface. To verify if pericarditis may be regarded as a marker of extensive MI, 60 patients with anterior or inferior MI admitted to the Coronary Care Unit within 6 hours from onset of symptoms, were studied by clinical, electrocardiographic and enzymatic parameters. 20 patients developed left ventricular failure (LVF) assessed by clinical, radiologic and hemodynamic indexes (15 mmHg has been considered the upper normal value for mean wedge pulmonary pressure). 9 of the 11 patients with pericarditis (PP) had LVF, versus 11 of the 49 non PP group (P = 0.002). Life threatening arrhythmias (ventricular tachicardia and fibrillation) appeared in 5 of the 11 PP versus 7 of the 49 non PP group (P = 0.04). No significant difference has been found between the two groups concerning the inhospital mortality. In a follow-up of 3 to 18 months, no difference in mortality was observed, while the functional recovery in the PP group was significantly worse (I and II versus III and IV New York Heart Association classes P = 0.003). Higher sigmaST values were found in precordial maps of the PP group, on admission (P = 0.03). After a deep spontaneous fall, sigmaST showed a reelevation which was similar in the two groups. SigmaR showed a greater % decrease however not statistically significant in PP. Creatinekinase enzymatic infarct size was significantly higher in PP group (P = 0.0002). It is concluded that pericarditis is a clinical marker of extensive MI and may be useful in evaluating prognosis and effectiveness of therapeutic interventions in MI.

Adult↗

[Precordial mapping and enzymatic analysis for estimating infarct size in man. A comparative study (author's transl)].

To investigate the relationships between electrocardiographic and enzymatic indexes of infarct size (I.S.), a group of 19 patients with anterior infarction was studied by serial precordial mapping and CPK curves analysis. The time course of ST and QRS changes was examined and a sharp, spontaneous fall of sigmaST was shown to occur within 10-12 hours after onset of symptoms, followed by a gradual rise. sigmaST on admission appears to be a poor predictor of subsequent enzymatic I.S. (r=0.49). Good correlations with I.S. were observed, for sigmaST at 48-96 hours (r=0.82) and, especially, for the percent decrease of sigmaR, with respect to the initial values (deltaR%), (r=0.94).

Adult↗

Prognostic significance of serum lactic acid dehydrogenase in Ewing's tumor of bone.

Pretreatment serum lactic acid dehydrogenase (LDH) levels were examined in 82 patients with Ewing's tumor of bone (23 metastatic and 59 localized). The percentage of patients with increased serum LDH levels was significantly higher in the metastatic group than in the group of patients with localized disease (87 vs. 45%). After treatment with combined therapy, in this latter group the recurrence rate was significantly higher in patients with elevated serum LDH levels at admission than in those with normal serum LDH levels (50 vs. 9%). Of the 16 patients with localized disease who relapsed, 13 (81%) had elevated serum LDH levels at the time of recurrence. These results indicate that in Ewing's tumor serum LDH levels may serve as useful prognostic markers and could be valuable in monitoring the effectiveness of combined therapy.

Adolescent↗

Toward an in vitro test for the diagnosis of allergy to penicillins. Synthesis, characterization, and use of beta-lactam and beta-lactam metabolite poly-L-lysines which recognize human IgE antibodies.

Conjugates of poly-L-lysine (PLL) containing a penicillin or a penicilloyl residue were prepared and characterized by 1H NMR and by size-exclusion (SE) HPLC. These conjugates were used in a radio allergo sorbent tests (RAST) test for the determination of allergy toward beta-lactams. The chemiometric evaluation of the data indicates that allergy to amoxycillin is different from allergy to the other beta-lactams tested. Furthermore, careful chemical characterization of the conjugates appears to be crucial to obtain meaningful information from the RAST data.

Chromatography, High Pressure Liquid↗

A 38 kDa nuclear protein is involved in the retention of an antisense oligonucleotide directed against cytosolic phospholipase A2.

Recent studies suggest that antisense phosphorothioate oligonucleotides (APO) are useful tools not only to impair gene expression, but also to modify the splicing of pre-mRNA, as the classical view that they act by suppressing the translation of mature mRNA has been challenged by several examples showing their nuclear site of action. In this work we show that an APO directed against cytosolic phospholipase A2 (cPLA2) mRNA localises in the nucleus and interacts with a specific nuclear protein.

Base Sequence↗

Retinoids and cancer: antitumoral effects of ATRA, 9-cis RA and the new retinoid IIF on the HL-60 leukemic cell line.

OBJECTIVE: To compare the antitumoral effects of all-trans retinoic acid (ATRA) and 9-cis retinoic acid (9-cis RA) with those of 5-OH,11-O-hydrophenanthrene (IIF), a new derivative of retinoic acid. MATERIALS AND METHODS: The effect of retinoids was tested on cell line HL-60. Cell differentiation and apoptosis were evaluated by morphological and biochemical analysis as BCL-2 protein and by DNA fragmentation assay. The ability to activate retinoic acid receptors (RAR) and/or retinoid X receptors (RXR) and to modulate gene expression was determined by transactivation assay. RESULTS: With cell line HL-60, the antiproliferative effect of IIF was stronger than that of ATRA and 9-cis RA. Following retinoid treatment, cells appeared to differentiate and apoptotic cells were observed. The appearance of DNA laddering and a decrease in the amount of BCL-2 protein confirmed apoptosis. IIF transcriptionally activated RXR-gamma more than RAR-alpha. CONCLUSION: The findings indicate that IIF transcriptionally activates RXR-gamma preferentially, induces apoptosis and has a more antiproliferative activity than ATRA and 9-cis RA on cell line HL-60.

Animals↗

Effect of a new derivative of retinoic acid on proliferation and differentiation in human neuroblastoma cells.

Neuroblastoma, a tumor originating from the sympathetic nervous system, is the most common extracranial malignant solid tumor of childhood. Human neuroblastoma cells may differentiate in vitro under treatment with a variety of biological agents and drugs. Among these, retinoic acid (RA) is quite potent and its effectiveness as a therapeutic agent is now being evaluated in clinical trials. As its pleiotropic biological activities may produce side-effects limiting clinical use, it is important to find new compounds that present the same effectiveness together with few side-effects. In this study we have explored the action of IIF, (pat. WIPO W0 00/17143) a new derivative of RA, as a differentiation inducer in the human neuroblastoma cell line TS12. In the same cell line, we have also compared the effect of IIF with that of all trans RA (ATRA) and of 9 cis RA (9cRA), with respect to morphological and biochemical differentiation and growth inhibition. Treatment with IIF resulted in a strong inhibition of proliferation and in a marked induction of neuronal differentiation as revealed by neurite extension, increase of actylcholinesterase (AchE) specific activity and tyrosine hydroxylase (TH) expression. The results demonstrate the effectiveness of this new retinoid as a differentiation inducer on neuroblastoma cells TS12. Furthermore, the differentiation-promoter and antimitotic activities of IIF were on the whole more pronounced than those of ATRA and 9cRA. Therefore our study suggests the evaluation of the new retinoid IIF as a therapeutic approach in the treatment of neuroblastoma.

Alitretinoin↗

The prognostic value of serum alkaline phosphatase in osteosarcoma of the limbs.

The values for serum alkaline phosphatase were evaluated in 340 patients affected with osteosarcoma of the limbs. The percentage of patients with high values for the enzyme at the onset of disease was significantly higher in the 69 cases who presented with metastases at the time of diagnosis, as compared to the 271 cases in which the neoplasm still appeared to be localized (81% vs 62%: p less than 0.001). In this last group of patients, treated with neoadjuvant chemotherapy, an evident relationship between values for alkaline phosphatase and prognosis was demonstrated. The percentage of patients who developed metastases was in fact 22% in the group with normal serum values for the enzyme at the onset of the disease and 40% for the patients with high values of the same (P less than 0.001). These data confirm the prognostic value for serum alkaline phosphatase in osteosarcoma, which should be taken into consideration when planning chemotherapy and in classifying patients for randomized therapeutic studies.

Adolescent↗

Retinoids and cancer: antitumor effect of ATRA and of a new derivative of retinoic acid, IIF, on colon carcinoma cell lines CaCo-2 and HT-29.

Vitamin A and its metabolic forms, like all-trans retinoic acid (ATRA), are used with promising results in the treatment of many tumors. Two major problems in the clinical use of retinoids are that the doses needed for successful treatment are often toxic, leading to "hypervitaminosis A syndrome" and that patients often develop drug resistance. In order to find compounds that can overcome these problems, many new derivatives of retinoids have been synthesized and tested. Here we present a study on the effect of a new derivative of retinoic acid, IIF (pat. WIPO W0 00/17143), on growth and differentiation of two colon carcinomna cell lines, CaCo-2 and HT-29, with different degrees of tumorigenicity, the second one being more undifferentiated. The effect of IIF was compared with that of ATRA, whose antitumoral action on colon cancer cells and other tumoral cells is widely described in the literature. Besides exerting a strong antiproliferative effect, even higher than that of ATRA, IIF induced cellular differentiation, as demonstrated by the appearance of morphological (domes and microvilli formation) and biochemical (alkaline phosphatase induction) markers. Therefore, these findings indicate the new retinoid IIF as a possible candidate in the treatment of colon cancer.

Antineoplastic Agents↗

[Prevalence of risk factors for ischemic heart disease in a northern Italian adult population].

The aim of this study is to measure the prevalence of cardiovascular risk factors in Tavazzano (Lodi) inhabitants, in order to implement efficacious and preventive strategies at community level. In 1998 the target population consisted of 2055 adults (males and females) aged 35-64, living in Tavazzano (Lodi province). The examined population was made of 856 subjects (399 males and 457 females), with a participation rate equal to 41,6%. A questionnaire concerning medical history and life habits such as: smoking, alcohol consumption and physical activity was administered to each participant. Height, Weight, Systolic and Diastolic Blood Pressure, Fasting Blood Glucose, Total Cholesterol and triglycerides were collected. A 12-leads electrocardiogram, evaluated both with standard clinical criteria and Minnesota Code, was done for each subject. The results show a high prevalence of modifiable cardiovascular risk factors: hypertension (25,2%), smoking (26,1%), obesity (14,6%), hypercholesterolemia (27,5%), low physical activity (39,6%) mainly in males and with an increasing trend with age. These data indicate the need of preventive programmes addressed to the general population and to "subjects at risk", according to the National Health Plan 2003-2005.

Adult↗

A search for multidrug resistance modulators: the effects of retinoids in human colon carcinoma cells.

The development of multidrug resistance (MDR) is one of the major causes of failure in cancer therapy. The use of cell lines with acquired resistance to anticancer agents represents a very good tool for investigation into the possibility of reversal of MDR. In this study the ability of all-trans-retinoic acid (RA) and its derivative 6-OH-11-O-hydroxyphenanthrene (IIF; pat. WIPO W000 /117143) as antitumor agents was investigated in the human colon carcinoma cell line LoVo and in the counterpart resistant derivative LoVo/MDR cell line. Cell proliferation was measured by MTT assay, apoptosis was evaluated using DNA fragmentation and Annexin V detection assay. Retinoids suppressed cell proliferation in a time- and dose-dependent manner. Interestingly, IIF was significantly more effective than RA, particularly on LoVo/MDR cells. RA and IIF induced apoptosis in both cell lines, with IIF effect significantly higher than that of RA. Furthermore, on the basis that MDR phenotype is often caused by drug efflux due to overexpression of the membrane P-glycoprotein (P-gp), it was demonstrated that RA and IIF reduced P-gp synthesis in LoVo/MDR cells. Our results suggest that IIF could be a powerful tool in the development of colon carcinoma treatments, even when tumor cells present an MDR phenotype.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Prostaglandins and cyclic nucleotides as effectors in non-lymphocyte mediated surveillance processes ( short review).

This paper reviews the evidence pointing to a role of prostaglandins and cyclic AMP in the regulation of surveillance processes against transformed cells carried out by activated monocytes macrophages and natural killer (NK) cells. Specific topics of discussion include: (a) the regulation of monocyte/macrophage system and NK cells by prostaglandins and cyclic AMP; and (b) the possible immunomodulatory role of thromboxanes generated by activated monocytes and macrophages. Also the role of cyclic AMP dependent and independent protein kinases as well as their link with oncogenes is briefly reviewed.

Cell Division↗