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Biomedical subjects

S Marini

Publications and source records attributed to S Marini.

71 records · Page 4Linked to original sources

Serotonin S2 receptors blockage and generalized anxiety disorders. A double-blind study on ritanserin and lorazepam.

Serotonin (5-HT) and 5-HT receptors are involved in mood disturbances, such as anxiety and depression. Ritanserin is a new substance with highly selective blocking activity on S2 receptors for 5-HT in the central nervous system. Ritanserin, (20 mg daily) and lorazepam (5 mg daily) were administered to 24 patients suffering from generalized anxiety disorders (DSM III), in a double-blind fashion for six weeks. The results obtained showed comparable improvement in almost all patients with both drugs. Future studies should pay particular attention to psychosomatic disturbances, depressed mood and dysthymic-like disorders, in which ritanserin seems to be more efficacious, according to the best responding items of the general anxiety check list used.

Adolescent↗

Surface glycoproteins of influenza virus increase cell-mediated immunity functions in mice.

T-lymphocyte blastogenic response to Concanavalin A, interleukin-2 (IL-2) production and NK cell activity were studied in three groups of Balb/c mice infected with intranasal inoculum of A/Chile/1/83 (H1N1) influenza virus, vaccinated with same virus glycoproteins and infected fifteen day after vaccination. Virus infection results in T-cell function impairment. In fact T-cell blastogenic response and IL-2 production are profoundly decreased as early as 24 hours, whereas NK cell activity is depressed only later. Instead viral glycoprotein vaccination induces an enhancement of CMI related parameters and protects the host from virus immunosuppressive effects.

Animals↗

Evidence for serotonin-S2 receptor involvement in analgesia in humans.

The possible analgesic activity of ritanserin (a new very selective and potent serotonin-S2 antagonist) was studied (double-blind) in humans. A significant increase in nociceptive flexion reflex threshold and subjective pain threshold was observed after five days of treatment, while treatment with placebo did not induce any change. The effects of ritanserin were not reversed by either naloxone or saline (double-blind) administration. Our data suggest a possible role of serotonin-S2 receptors in analgesia.

Adult↗

Influence of interferon on the functional expression of natural killer target structures of murine lymphoma cells.

Murine lymphoma cells (YAC-1), induced by Moloney leukemia virus, nontreated (YAC) or pretreated in vitro with interferon (YAC-IF), were tested for their susceptibility to natural killer (NK)-mediated cytolysis. In line with previous reports YAC-IF were less susceptible to NK lysis than YAC cells. In cold competition assay, YAC-IF inhibited cytotoxicity to a lesser extent than YAC lymphoma when labeled target YAC cells were used. However, when radioactive YAC-IF cells were used as targets, cold competition attained with both YAC and YAC-IF was essentially the same. Furthermore, effector splenocytes, depleted of NK effector cells through immunoabsorption on YAC monolayer, were inactive against both YAC and YAC-IF targets. On the other hand, effector lymphocytes, absorbed on YAC-IF monolayer, retained NK activity against YAC cells but not against YAC-IF targets. These results are compatible with the hypothesis that interferon (IF) modulates negatively a subset of "interferon-susceptible" (IFS) NK target structure(s) (TS) of YAC cells, which would then express membrane determinants not functionally present on YAC-IF cells. On the other hand YAC and YAC-IF cells share "interferon-resistant" (IFR) TS not affected by pretreatment with IF. In order to test whether IFS X TS and IFR X TS are present on the same cell or clonally distributed, YAC cells were cloned and tested for NK susceptibility following IF pretreatment. The results did not support the hypothesis of a clonal distribution of both IFS X TS and IFR X TS since IF pretreatment of all clones, obtained by limiting dilution, resulted in a net impairment of target susceptibility to NK effector cells.

Animals↗

Neuroendocrine effects of setoperone: a new neuroleptic drug.

Setoperone (R 52245), a serotonin S2 and dopamine D2 receptor blocker, was tested on eight healthy male volunteers, receiving 5 or 40 mg orally, in order to assess the modifications of plasma prolactin levels, as an index of receptor blocking activity. Both doses significantly increased plasma levels, confirming the dopamine blocking activity. In vitro and in vivo studies have shown serotonin S2 receptor blockade and lysergic acid diethylamide antagonist activity. Setoperone is proposed as a possible new neuroleptic drug.

Adolescent↗

A miniaturized cell-mediated cytotoxicity assay with human effector mononuclear cells.

A miniaturized method (Microtest, MIT) for detecting natural killer (NK) and antigen-elicited cell-mediated cytotoxicity has been developed. It retains the sensitivity and the efficiency of conventional macroassay (Macrotest, MAT). In comparison with the standard MAT, MIT provides a 5-fold reduction in the number of effector and target cells without changing the final reaction volume. This avoids the excessive relative evaporation that could occur in microassays employing limited reaction volumes. Moreover the use of V-bottom microtiter plates allows the recovery of 0.15 ml of supernatant, thus increasing the efficiency of 51Cr recovery. MIT was adopted for the evaluation of the NK activity of untreated or interferon (IFN)-treated human mononuclear cells (MNC) and for cold-inhibition and cytotoxic T-lymphocyte (CTL) assays. In the experiments performed with both macro and micro assays, comparable values of the percentage of specific lysis and of the number of lytic units were found. The slopes of the curves obtained with MIT are generally slightly lower than those detectable with MAT. The Pearson coefficient r2 is generally better for the macroassay although it can be considered acceptable in the microassay. The MIT described here appears to be a useful method, especially for providing information on natural resistance and cytotoxic T-lymphocyte systems in a number of pathological conditions characterized by a small recovery of effector cells from standard blood collection for analytical purposes.

Cell Line↗

Life-span, tumor incidence, and natural killer cell activity in mice selected for high or low antibody responsiveness.

Biozzi mice selected for high (H) or low (L) antibody responsiveness to natural antigens have been followed for their entire life-span to examine their pathology at death. As previously found in selection I, shorter life-span and higher lymphoma incidence were observed in L responder mice than in H responder mice selected for antibody responsiveness to sheep red blood cells (selection II). In mice selected for antibody responsiveness to Salmonella flagellar antigens (selection III), similar life-span and similar lymphoma incidence were found in H and L responder mice. Natural killer (NK) cell activity, as assessed in spleen cells from young mice, was lower in L than in H responder mice of selection I but higher in L than in H responder mice of both selections II and III. All these results indicate that longevity and lymphoma incidence at death are independent of NK cell activity in mice selected for H or L antibody responsiveness to natural antigens. Furthermore, genetic selection for antibody responsiveness does not always appear to influence life-span and lymphoma incidence.

Animals↗

Drug-mediated increase of susceptibility of human lung cancer to NK or LAK effector cells.

Previous studies in murine models have shown that in vivo or in vitro treatment of tumor cells with mutagenic triazene compounds (TZC) lead to the appearance of novel drug-mediated tumor antigens (DMTA) capable of eliciting graft resistance in syngeneic hosts. This phenomenon, defined as 'chemical xenogenization' (CX), could be of potential value for immunochemotherapy of human neoplasias. It was also shown that TZC modulate NK sensitivity of murine tumor cells. Therefore, experiments were conducted to evaluate whether susceptibility of a human lung adenocarcinoma cell line (H125) to natural cytotoxic effectors could be affected by treatment with an in vitro active TZC. The results showed that drug treatment of H125 line leads to heritable increase of susceptibility to NK and LAK cells. Moreover, increased binding between effector and drug-treated target cells was observed. Additional studies on HLA antigens showed that changes in HLA-ABC molecule expression were probably not involved in TZC-induced increase of NK/LAK susceptibility. These results suggest that TZC treatment of a human tumor could result in increased expression of membrane structures recognized by natural cytotoxic effector cells. Further studies are required to explore whether these changes are generated by mutational events correlated with TZC-induced CX of human cancer cells.

Antigens, Neoplasm↗

Pregnancy does not induce or worsen retinal and peripheral nerve dysfunction in insulin-dependent diabetic women.

In order to verify whether pregnancy induces or worsens diabetic retinopathy or somatic and autonomic neuropathy, 16 insulin-dependent diabetic (IDDM) pregnant women, 14 age-matched nondiabetic pregnant women, and 12 IDDM nonpregnant women matched for age and disease duration were studied. Plasma glucose, HbA1c, and fructosamine were repeatedly assayed during pregnancy. Retinopathic and neuropathic endpoints were evaluated through ophthalmoscopy, electrophysiology of left peroneal and sural nerves (motor and sensory conduction velocities), and cardiovascular autonomic tests (deep breathing, cough test, lying-to-standing). In the IDDM pregnant women, evaluations were performed three times during pregnancy and 6 months after delivery. Good metabolic control was achieved during pregnancy. At baseline, nine IDDM pregnant women did not show signs of retinopathy, and seven had nonproliferative retinopathy. Only one patient showed worsening during pregnancy, but she improved after delivery. Motor conduction velocity, significantly lower in IDDM pregnant women, progressively improved, and, in the third trimester, was not significantly different from that of nondiabetic pregnant women. At baseline, none of the IDDM pregnant women had abnormal responses to cardiovascular autonomic tests. During pregnancy, the response to deep breathing appeared temporarily reduced in all pregnant women, possibly due to lowered ventilatory excursion at the end of pregnancy. In IDDM women with minimal or no retinopathy, and subclinical or no peripheral neuropathy, pregnancy does not appear to induce or worsen these complications.

Adult↗

Correlation between osteoarthritic cartilage damage and levels of proteinases and proteinase inhibitors in synovial fluid from the knee joint.

Matrix metalloproteinases (MMPs) in the synovial fluid are responsible for collagen breakdown during physiologic cartilage turnover and the pathologic destruction of the cartilage. We measured the levels of MMPs, specific tissue inhibitors of metalloproteinases (TIMPs), and interleukin-6 (IL-6) in synovial fluid from the knees of 36 patients with cartilage lesions subdivided according to severity based on arthroscopic findings. Lesions were classified as mild (group 1, edema with no disruption of the surface), moderate (group 2, open lesions without exposure of subchondral bone), or severe (group 3, exposure of subchondral bone). Zymography (gel electrophoresis in the presence of hydrolizable substrates) showed a 60-kd band in all samples. A second band (94-kd) was found exclusively in specimens from groups 2 and 3, and a third band (110-kd) was present only in group 3. Concentrations of 2 of the most important modulators of MMP activity, TIMP-1 and IL-6, were measured. TIMP-1 levels did not vary significantly with the severity of cartilage damage. Linear regression analysis revealed a significant positive correlation between TIMP-1 and IL-6 in groups 1 and 2. These data indicate that the severity of the cartilage damage corresponds with MMP activity. The correlation between IL-6 and TIMP-1 in groups with mild and moderate damage suggests a regulating mechanism that is absent in severe lesions.

Adult↗

Synthesis, cytotoxic effect and antiviral activity of 1-(beta-D-arabinofuranosyl)-5-bromo-N4-substituted cytosine and 1-(beta-D-arabinofuranosyl)-5-bromo-4-methoxypyrimidin-2(1H)-one derivatives.

A convenient and mild synthesis of 5-bromo-N4-substituted-1-(beta-D-arabinofuranosyl)cytosine and 5-bromo-O4-methyl-1-(beta-D-arabinofuranosyl)pyrimidin-2(1H)-one derivatives by selective oxyfunctionalization of the corresponding 4-thionucleosides with 3,3-dimethyldioxirane is reported. The cytotoxicity and the antiviral activity against parainfluenza 1 (Sendai virus) of all new synthesized products are also reported.

3T3 Cells↗

Immuno-chemotherapy of advanced colorectal cancer with alpha-2a interferon and 5-fluorouracil. Immunopharmacological studies.

Twelve patients with metastatic colorectal cancer received alternating cycles of low immunomodulating doses of alpha-IFN + 5-Fluorouracil (5-FU) or 5-FU alone. Hematological, biochemical and physical evaluation showed that both treatment cycles were well tolerated. However, transient fever and moderate flu-like symptoms were observed following alpha-IFN administration. Treatment with 5-FU alone produced long-lasting inhibition of CD8+ T lymphocytes, but did not depress NK activity (NKA). Combined treatment with alpha-IFN produced a short-term increase of NKA and antagonized the effect of 5-FU on CD8+ cells on day 5 of the cycle. Parallel studies on in vitro models showed antiproliferative effects of 5-FU on PHA-stimulated MNC and confirmed the preferential inhibition of CD8+ cells. Pretreatment with alpha-IFN did not reverse the effect of 5-FU on CD8+ lymphocytes, but partially protected MNC from the toxic effects of the drug. This was presumably due to the cytostatic effects induced by alpha-IFN on MNC before exposure to the cycle-specific antineoplastic agent. This investigation suggests that alpha-IFN could play a positive role in immuno-chemotherapy of colorectal cancer through multiple mechanisms not entirely related to direct antitumor effects of the agent.

Antineoplastic Combined Chemotherapy Protocols↗

Non cardiopatic and cardiopatic beta thalassemic patients: quantitative and qualitative cardiac iron deposition evaluation with MRI.

PURPOSE: Cardiomyopathy is one of the major complications of b thalassaemia major as a result of transfusional iron overload. The aim of our study is to evaluate with MR if there is any difference of iron deposition signal intensity (SI) or distribution between non-cardiopathic and cardiopathic thalassaemic patients in order to establish if there is a relationship between cardiopathy and iron deposition. MATERIALS AND METHODS: We studied 20 patients affected by b thalassaemia major, of whom 10 cardiopathic and 10 non-cardiopathic, and 10 healthy volunteers as control group. Serum ferritin and left ventricular ejection fraction were calculated in thalassaemic patients. All patients were examined using a 1.5 MR unit with ECG-gated GE cine-MR T2*-weighted, SE T1-weighted and GE T2*-weighted sequences. In all cases, using an adequate ROI, the myocardial and skeletal muscle signal intensity (SI), the myocardial/skeletal muscle signal intensity ratio (SIR) and the SI average of the myocardium and skeletal muscle were calculated for every study group. The qualitative evaluation of iron deposition distribution was independently performed by three radiologists who analyzed the extension, the site and the morphology of iron deposition on the MR images and reported their observations on the basis of a four-level rating scale: 0 (absent), 1 (limited), 2 (partial), 3 (widespread deposition). The result of quantitative and qualitative evaluations were analysed with statistical tests. RESULTS: Cardiac iron deposition was found in 8/10 non-cardiopathic thalassaemic patients and in all cardiopathic thalassaemic patients. We noticed a significant SI difference (p>0.05) between the healthy volunteer control group and the thalassaemic patients with iron deposition, but no significant SI difference in iron deposition between non-cardiopathic and cardiopathic thalassaemic patients in the areas evaluated. The qualitative evaluation revealed a different distribution of iron deposition between the two thalassaemic groups, with more widespread distribution in cardiopathic patients. CONCLUSIONS: We found cardiac iron deposition also in non-cardiopathic b thalassaemic patients and a qualitative difference in cardiac iron distribution between non-cardiopathic and cardiopathic patients. The qualitative evaluation of cardiac iron deposition was useful for an easier classification of the disease, bypassing the SI quantitative value which is affected by the extremely uneven distribution of iron deposition and by the sampling technique used. MR evaluation of non-cardiopathic thalassaemic patients may be useful to evaluate early iron deposition and to establish the most suitable chelation therapy.

Adult↗

[Allergy to cow's milk proteins in childhood: the authors' personal experience and new diagnostic and therapeutic proposals].

Cow's milk protein is quite commune in infancy (2-3% in first year of age). Casein, beta-lactoglobulin and alpha-lactalbumin are the main allergens of cow's milk. The authors describe the immunological reaction involved in IgE synthesis and consequential inflammation after ingestion of cow's milk proteins and present soy and protein extensive hydrolysates as alternative diets for children with cow's milk allergy. Moreover, the authors present their studies on immunogenicity of hydrolysed formulae. At the end they suggest the therapeutic strategy in the cow's milk protein allergy.

Child, Preschool↗

[The inhalational therapy of respiratory pathology].

The inhalation of aerosolized drugs for therapeutic purpose has been used for many years in respiratory diseases as asthma, chronic bronchitis, cystic fibrosis. Therapeutic aerosols have the advantages to deliver active substances directly to the site of disease, without systemic side effects, to produce a more rapid clinical response, to avoid barriers to the absorption of drugs such as the gastrointestinal tract. We review the mechanisms and the site of lung deposition and the range of devices that can provide an effective aerosol such as metered dose-inhaler and spacers. Besides drugs as cromolyn, beta-2-agonists and topical steroids, recently new inhalation therapies were proposed using antiviral drugs (interferon), pentamidine for Pneumocystis carinii in immunocompromised host, inhalation of attenuated virus (measles) for active immunization. However there is a need for further work in this area.

Administration, Inhalation↗

[Necessity and validity of standard models for experimental preclinical evaluation of biomaterials. An example of biologic characterization of a hydroxyapatite-based implant material].

A large number of methods are now available for the preclinical screening of implantable materials concerning their biocompatibility and their ability to stimulate tissue formation. In vitro techniques represent a very useful tool, since this way we can realistically simulate the biological events which occur in vivo at the bone-implant interface. In the present study scanning electron microscopy and light microscopy observations were performed in order to assess the effect of an hydroxyapatite granulate on cell behaviour and morphology. Uptake of proteins to hydroxyapatite surface has been also investigated by comparing the amounts adsorbed after incubation with bovine serum albumin and bovine pancreaticamilase. According to our preliminary observation cells do not show signs of toxicity or inhibition of cell growth even after 14 days of co-culture with hydroxyapatite. Granules were covered by an uninterrupted cell layer by day seven. Even after two days micrographs show cells anchored and spread over the surface of the underlying granules, with a flattened and stellate shape. Such a morphology indicates a very high cellular activity, suggesting that the interaction with hydroxyapatite seriously increased metabolism. Measurements of protein adsorption on the hydroxyapatite surface show that changes in the size of particles affect the binding of proteins, while, in the case of granular hydroxyapatite, despite changes in size of granules, variations of protein adsorption were not observed, neither in relation to their different isoelectric point. Our preliminary results represent a good example of the opportunities presented by an experimental in vitro model.

Biocompatible Materials↗