New Echocardiographic Techniques in the Evaluation of Left Ventricular Mechanics in Subclinical Thyroid Dysfunction

The new echocardiographic techniques for the study of physiopathological intramyocardial phenomena include video densitometry (VD), integrated backscatter (IBS), and color Doppler myocardial imaging (CDMI). Being more independent from cardiac load and from rotational and translational heart motion, these new sensible, noninvasive techniques such as CDMI and IBS show a real incremental value in comparison with conventional echocardiography and allow to detect subtle functional and textural abnormalities of intramural myocardium, partially undetectable by conventional two-dimensional Doppler echocardiography. Subclinical thyroid dysfunction (STD), both in its hypo- and hyperthyroidism form, has a relatively high prevalence in general population (9–15% with a lower percentage of adult males), hence it could be very useful to study more deeply heart involvement in these physiopathological conditions and understand the complex relationship between thyroid and heart. The use of these new ultrasonic techniques in subclinical hypothyroidism helps to detect the early simultaneous involvement of both cardiac cycle phases, which causes a decrease of intramyocardial contractility and an impairment of both active and passive phases of diastole. In subclinical hyperthyroidism, these new ultrasonic techniques permitted to discover more complex and different early cardiac abnormalities of both systolic and diastolic phases.     

Color Doppler and hormone replacement therapy: the role of thromboxane and plasma viscosity.

The aim of the study was to evaluate the plasma thromboxane and plasma viscosity in relation with Doppler flow parameters in postmenopausal patients treated with hormone replacement therapy. Thirty-two postmenopausal (follicle-stimulating hormone > 40 IU/l and estradiol < 100 pmol/l) women (mean age +/- SD, 54.7 +/- 2.9 years) participated in the study and were submitted to continuous estradiol transdermal supplementation and 12-day courses of medroxyprogesterone acetate every second month. Doppler resistances at the level of the uterine and internal carotid arteries, thromboxane plasma levels and plasma viscosity were analyzed in basal condition and after 1, 3 and 6 months. During hormone supplementation, the pulsatility index significantly decreased at the level of the analyzed arteries. Similarly, plasma thromboxane levels and plasma viscosity were significantly reduced. Significant correlations were found between thromboxane plasma concentrations, plasma viscosity and uterine artery resistances. Thus hormone replacement therapy seems to be responsible for both direct and indirect modifications at the level of the vessel wall physiology.     

Protective effect of silymarin in antigen challenge- and histamine-induced bronchoconstriction in in vivo guinea-pigs

The effects of silymarin on bronchoconstriction induced by antigen challenge and on post-antigen challenge hyperresponsiveness to substance P were evaluated in sensitized guinea-pigs. Silymarin significantly decreased the bronchoconstriction due to antigen administration in the early phase of the response. In contrast, the dose-response curve for substance P recorded 1 h after antigen challenge was not modified by pretreatment with silymarin. The influence of the flavonoid on hyperresponsiveness to histamine in propranolol- and PAF (platelet-activating factor)-treated animals was also assessed. Silymarin did not affect hyperresponsiveness to histamine induced by either propranolol or PAF although it had inhibitory activity on the bronchial contractile response to the autacoid. These results suggest that silymarin has a protective effect in the early phase of allergic asthma, an effect, which may be related to a negative influence of the flavonoid on bronchial responsiveness to histamine.     

Plasma long-chain polyunsaturated fatty acids and neurodevelopment through the first 12 months of life in phenylketonuria

The aims of the study were to examine the relationship between long-chain polyunsaturated fatty acid (LCPUFA) status at diagnosis of phenylketonuria (PKU) and neurodevelopment through the first 12 months of life, and to assess whether any difference exists between infants breastfed and bottlefed in the first days of life on the basis of LCPUFA status. Twenty infants with PKU were prospectively examined through the first year of life. Plasma fatty acids were measured in infants at diagnosis. Plasma phenylalanine levels were determined monthly. Main outcome measures were the Bayley Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) at 5 and 12 months of age, and the visual function at 12 months, evaluated by P100 wave latencies with visual evoked potentials. A higher PDI score was associated with higher plasma arachidonic acid at diagnosis (adjusted correlation coefficient of PDI at 5 months, r=0.38, p=0.05). P100 wave latency at 15 minutes of arc (15') was associated with the early plasma arachidonic acid (adjusted r=-0.56, p=0.02) and phenylalanine levels at 12 months (adjusted r=0.22, p=0.05). No association was found between MDI score and any essential fatty acids. Breastfed infants exhibited higher plasma arachidonic acid (mean difference, delta, =3.4%; 95% confidence interval [CI]=1.2-5.6%) and shorter P100 wave latency at 15' (delta=-21 ms, 95%CI=-30 to -12) than bottlefed infants. Within the population of this study, a weak positive association has been found between plasma LCPUFAs at diagnosis (higher in breastfed infants) and neurodevelopmental indices through the first year of life.     

HIV prevention and adolescents: a sample survey on Italian high school students

This article resulted from a survey carried out by some researchers of the Telefono Verde AIDS (TVA-National AIDS Help-Line) of the Istituto Superiore di Sanità, with the collaboration of some colleagues of the Segreteria per le Attività Culturali. It is also a summary of strategies of intervention against HIV/AIDS for young people implemented by the Italian Ministry of Health. The study was developed within the context of the workshops on HIV/AIDS education carried out since 1995 by some researchers of TVA. These workshops fall within some other initiatives arranged by the Segreteria per le Attività Culturali for the diffusion of scientific and technological information. Our study aimed at assessing the level of knowledge on HIV/AIDS among some different high-school students. Data processing points out a widespread and quite good level of knowledge on HIV/AIDS in general and particularly on ways of transmission and prevention measures. Results obtained could not be generalized because the sample involved in the survey represented a privileged target, already sensitive to the issues concerning HIV infection and AIDS dealt with in the context of specific teaching programmes.     

Targeted delivery of tumor necrosis factor-alpha to tumor vessels induces a therapeutic T cell-mediated immune response that protects the host against syngeneic tumors of different histologic origin.

PURPOSE: We sought to demonstrate that a single systemic administration of L19mTNFalpha (a fusion protein constituted by the scFv L19 specific for the oncofetal ED-B domain of fibronectin and tumor necrosis factor alpha, TNFalpha) in combination with melphalan induced complete and long-lasting tumor eradication in tumor-bearing mice and triggered the generation of a specific T cell-based immune response that protects the animals from a second tumor challenge, as well as from challenges with syngeneic tumor cells of different histologic origin. Experimental Design and RESULTS: Treatment with L19mTNFalpha, in combination with melphalan, induced complete tumor regression in 83% of BALB/c mice with WEHI-164 fibrosarcoma and 33% of animals with C51 colon carcinoma. All cured mice rejected challenges with the same tumor cells and, in a very high percentage of animals, also rejected challenges with syngeneic tumor cells of different histologic origin. In adoptive immunity transfer experiments, the splenocytes from tumor-cured mice protected naive mice both from C51 colon carcinoma and from WEHI-164 fibrosarcoma. Similar results were also obtained in adoptive immunity transfer experiments using severely immunodepressed mice. Experiments using depleted splenocytes showed that T cells play a major role in tumor rejection. CONCLUSIONS: The results show that the selective targeting of mTNFalpha to the tumor enhances its immunostimulatory properties to the point of generating a therapeutic immune response against different histologically unrelated syngeneic tumors. These findings predicate treatment approaches for cancer patients based on the targeted delivery of TNFalpha to the tumor vasculature.     

Cyclo-oxygenase-2 (Cox-2) expression and resistance to platinum versus platinum/paclitaxel containing chemotherapy in advanced ovarian cancer

Background  

Cyclo-oxygenase-2 (COX-2), the key enzyme in the conversion of arachidonic acid to prostaglandins, is involved in critical steps of tumor onset and progression, and is a strong predictor of chemotherapy resistance and poor outcome in advanced ovarian cancer. To our knowledge, no data has been reported until now about the association between COX-2 status and response to different chemotherapy regimens.