Characterization of myocardial tissue by ultrasound: backscatter]

One of the most important goals in Cardiology is to identify, noninvasively, the normal as well as pathological changes in structure and function of myocardial tissue in order to recognize their etiology and severity. Ultrasonic Tissue Characterization is an approach to define the physical state of the heart by the analysis of the pathological changes that modify cardiac tissue physical properties, therefore generating an ultrasonic signal alteration. Among the most practical types of analysis of this data is the acoustic parameters measurement, and measurements based on integrated backscatter have been utilized the most. Backscatter is the ultrasonic quantification reflected back to the transducer, therefore emanating from myocardial structures or "scatterers". This method has been used to study many patients with hypertrophy, cardiomyopathies, cardiac allograft rejection. But is the investigation of myocardial ischemia-viability one of the most clinically relevant applications because of the importance of selecting, non-invasively, and at a relatively low cost those patients with coronary artery disease in whom myocardial asynergy is noted by conventional echocardiography and/or angiography. The magnitude of alterations in backscatter measurements such as the cyclic variation of integrated backscatter are markers of myocardial viability and could better identify patients who stand to benefit the most revascularization procedures.     

Evidence of enzymatic degradation of insulin-like growth factor-binding proteins in the 150K complex during pregnancy.

Western ligand blot analysis of the different molecular forms of insulin-like growth factor-binding protein IGF-BP) in serum and plasma samples from 89 pregnant women has revealed a marked decrease, after the second month of pregnancy, in the 41.5 and 38.5K species (which are the binding units of the 150K complex) as well as in the 24K form. There was also a slight decrease in the 34K form, the 30K form was unaffected, and additional 21.5 and 20K bands appeared. Cross-linking experiments demonstrated the disapperance of a 49K band which is characteristic of the 150K complex. The alterations of the electrophoretic profile of the BPs were accompanied by a decrease in binding activity of up to 90%. Gel filtration at pH 7.4 confirmed that the decrease was essentially attributable to changes in the 150K complex BPs: 1) material eluting in the 150K zone contained only one third of the binding activity, as opposed to three quarters in reference material; 2) radiocompetition experiments illustrated the loss of affinity for IGF-I and IGF-II of the BPs extracted from the 150K complex; 3) ligand blot analysis revealed, in contrast with the virtual disappearance of the 41.5 and 38.5K forms, the appearance of a broad indistinct band at 30K and additional bands at 21.5 and 20K. With immunoblotting, the anti-IGF-BP-3 antibody, which specifically recognizes the 41.5 and 38.5K species, cross-reacted with this 30K material. The alterations of the BPs appeared to be enzymatic. When pregnancy serum was mixed with reference serum, the 41.5, 38.5, and 24K forms contributed by the reference serum were markedly reduced after 30 min of incubation at 37 C. However, these alterations could be prevented by incubation at either 0 or at 37 C in the presence of EDTA or aprotinin and could be curbed in the presence of high concentrations of phenylmethylsulfonylfluoride. Unmixed reference serum incubated at 37 C yielded an unchanged BP profile. Incubation of pregnancy serum with hypopituitary serum, which has elevated levels of the 34 and 30K BPs, resulted in a marked decrease in the 41.5 and 38.5K forms, a slight alteration of the 34K form, and no change in the 30K form. These findings suggest that during pregnancy, enzymatic (probably protease) activity either appears or is significantly increased in the circulation, which specifically degrades some of the IGF-BPs.(ABSTRACT TRUNCATED AT 400 WORDS)     

Tests for screening olfactory and gustatory function in school-age children.

OBJECTIVE: Determine the suitability of three tests based on the identification of familiar odors and tastes for the clinical assessment of olfaction and gustation in children. STUDY DESIGN AND SETTING: A total of 232 children aged 5 to 7 years from Sydney public schools and 56 adults aged 18 to 51 years participated in a cross-sectional study. RESULTS: The children demonstrated they can identify the majority of the 16 test odorants and 4 common tastes that describe gustatory function. The response distributions obtained for each test provide the basis for a set of normative data for young children. CONCLUSION: Olfactory and gustatory function can be determined in school-age children using the three tests described. SIGNIFICANCE: Currently no satisfactory clinical tests of olfaction and gustation for children or normative data are available. The present study resolves these shortcomings and provides normative data that can be used in the diagnosis of olfactory and gustatory impairment in school-age children.     

Dentifrices: some active agents

This article is an up to date about the most used active agents in dentifrices: cariostatic, anticalculus, antiplaque and desensitivity. The authors try a classification of them and discuss their advantages and possible side effects.     

In vitro and in vivo susceptibility of mouse megakaryocytic progenitors to strain i of parvovirus minute virus of mice.

OBJECTIVE: Intranasal inoculation of the i strain of the parvovirus minute virus of mice (MVMi) into immunodeficient SCID mice induces suppression of myeloid and erythroid progenitors in the bone marrow (BM) and lethal leukopenia. In the present study, we investigated whether the mouse megakaryocytic lineage was susceptible to MVMi. MATERIALS AND METHODS: In vitro and in vivo infections with purified MVMi were conducted and their effects on the megakaryocytic lineage studied. RESULTS: In vitro infection of BM cells showed a multiplicity of infection-dependent inhibition in the colony-forming ability of megakaryocytic progenitors (colony-forming unit megakaryocyte [CFU-MK]). Neutralization or heat inactivation of the virus abrogated this inhibition. Expression of the MVMi nonstructural-1 protein was detected in the in vitro infected and cultured megakaryocytic cells. In vivo, intranasal inoculation of a lethal dose of virus was incapable of producing significant thrombocytopenia, although an increase in mean platelet volume was observed. Significantly, in the BM of these animals, a progressive decrease in CFU-MK was noted from day 14 postinfection, with survival rates less than 1% by day 35 postinfection. At day 35 postinfection, intermediate megakaryocytic differentiation stages showed maintenance of the proportion and ploidy of cells and a moderate decrease in the total number of these cells per femoral BM. CONCLUSIONS: The results demonstrate that MVMi is capable of inhibiting the proliferative capacity of megakaryocytic committed progenitors both in vitro and in vivo. Moreover, the in vivo data show that depletion of BM CFU-MK is compensated by the system, and platelet counts in the peripheral blood are maintained close to normal values.     

Dopamine release during stress in the prefrontal cortex of the rat decreases with age.

The effects of aging on the stress-induced increases of dopamine and the dopamine metabolites 3,4-dihydroxyphenylaectic acid (DOPAC) and homovalinic acid (HVA) in the medial prefrontal cortex of the awake rat were investigated using microdialysis. In young rats (2-3 months) handling stress produced an increase of dopamine by 205% and of the dopamine metabolites DOPAC by 120% and HVA by 155% of baseline as maximal increases. In middle-aged rats (14 months) the increase of dopamine was significantly lower than in young rats (155% of baseline), while in aged rats (30 months) stress produced no significant increases of dopamine in the prefrontal cortex. These results indicate that the effects of stress on dopamine release in the medial prefrontal cortex of the rat diminishes during the normal process of aging.     

Sexual dimorphism in the parastrial nucleus of the rat preoptic area

This work investigates the possible existence of sex differences in the volume of the parastrial nucleus (PSN), a component of the preoptic area in the rat. The effects of postnatal (on day 1 after birth) male orchidectomy and female androgenization on this nucleus were studied. The volume of the PSN was greater in the control females than in the control males and postnatal treatments reversed this sexual dimorphism.     

Characteristics of lentiviral vectors harboring the proximal promoter of the vav proto-oncogene: a weak and efficient promoter for gene therapy.

Recent published data have shown the efficacy of gene therapy treatments of certain monogenic diseases. Risks of insertional oncogenesis, however, indicate the necessity of developing new vectors with weaker or cell-restricted promoters to minimize the trans-activation activity of integrated proviruses. We have inserted the proximal promoter of the vav proto-oncogene into self-inactivating lentiviral vectors (vav-LVs) and investigated the expression pattern and therapeutic efficacy of these vectors. Compared with other LVs frequently used in gene therapy, vav-LVs mediated a weak, though homogeneous and stable, expression in in vitro-cultured cells. Transplantation experiments using transduced mouse bone marrow and human CD34(+) cells confirmed the stable activity of the promoter in vivo. To investigate whether the weak activity of this promoter was compatible with a therapeutic effect, a LV expressing the Fanconi anemia A (FANCA) gene was constructed (vav-FANCA LV). Although this vector induced a low expression of FANCA, compared to the expression induced by a LV harboring the spleen focus-forming virus (SFFV) promoter, the two vectors corrected the phenotype of cells from a patient with FA-A with the same efficacy. We propose that self-inactivating vectors harboring weak promoters, such as the vav promoter, will improve the safety of gene therapy and will be of particular interest for the treatment of diseases where a high expression of the transgene is not required.     

Clinical recommendations for the use of everolimus in heart transplantation

Proliferation signal inhibitors (PSIs), everolimus (EVL), and sirolimus are a group of immunosuppressor agents indicated for the prevention of acute rejection in adult heart transplant recipients. Proliferation signal inhibitors have a mechanism of action with both immunosuppressive and antiproliferative effects, representing an especially interesting treatment option for the prevention and management of some specific conditions in heart transplant population, such as graft vasculopathy or malignancies. Proliferation signal inhibitors have been observed to work synergistically with calcineurin inhibitors (CNIs). Data from clinical trials and from the growing clinical experience show that when administered concomitantly with CNIs, PSIs allow significant dose reductions of the latter without loss of efficacy, a fact that has been associated with stabilization or significant improvement in renal function in patients with CNI-induced nephrotoxicity. The purpose of this article was to review the current knowledge of the role of PSIs in heart transplantation to provide recommendations for the proper use of EVL in cardiac transplant recipients, including indications, treatment regimens, monitoring, and management of the adverse events.