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AimsThe heterozygous phospholamban (PLN) mutation R14del (PLN R14del+/-) is associated with a severe arrhythmogenic cardiomyopathy (ACM) developing in the adult. “Superinhibition” of SERCA2a by PLN R14del is widely assumed to underlie the pathogenesis, but alternative mechanisms such abnormal energy metabolism have also been reported. This work aims to 1) to evaluate Ca2+dynamics and energy metabolism in a transgenic (TG) mouse model of the mutation prior to cardiomyopathy development; 2) to test whether they are causally connected.Methods and ResultsCa2+dynamics, energy metabolism parameters, reporters of mitochondrial integrity, energy and redox homeostasis were measured in ventricular myocytes of 8-12 weeks-old, phenotypically silent, TG mice. Mutation effects were compared to pharmacological PLN antagonism and analysed during modulation of sarcoplasmic reticulum (SR) and cytosolic Ca2+compartments. Transcripts and proteins of relevant signalling pathways were evaluated. The mutation was characterized by hyperdynamic Ca2+handling, similar to that induced by PLN antagonism. Albeit all components of energy metabolism were depressed at rest, functional signs of mitochondrial damage or energy starvation were absent and cell energy charge was preserved. The response of mitochondrial O2consumption to SERCA2a blockade was lost in mutant myocytes (SR-mitochondrial uncoupling) and ER-stress signalling was activated.Conclusions1) PLN R14del+/-loses its ability to inhibit SERCA2a, which argues against SERCA2a superinhibition as a mechanism of ACM; 2) depression of resting energy metabolism may at least partly reflect impairment of SR-mitochondrial coupling; 3) ER-stress may be an early factor in the pathogenesis.

The prelimbic division (PrL) of the medial prefrontal cortex (mPFC) is a cerebral division that is putatively implicated in the chronic pain and depression. We investigated the activity of PrL cortex neurons in Wistar rats that underwent chronic constriction injury (CCI) of sciatic nerve and were further subjected to the forced swimming (FS) test and mechanical allodynia (by von Frey test). The effect of blockade of synapses with cobalt chloride (CoCl

Introduction. Over the last decade several studies were done to assess the nutritional composition and effects of partial substitution of traditional protein sources with insect meal in animal health. The aim of this study was to assess the effect of dietary Tenebrio molitor (TM) meal supplementation on immune and cellular responses to external stimuli of intestinal mucosa and liver in poultry. Animals, material and methods. One-day old broiler chicks (Ross 708) were raised in 10 pens (8 birds/pen), and were divided in 2 groups. Two isonitrogenous and isoenergetic feeding plans were used (12.9 MJ ME/kg and 23.5% CP from day 1 until day 12; 13.3 MJ ME/kg and 21.3% CP from day 12 until day 25; and 13.5 MJ ME/kg and 19.6% CP from day 25 until slaughter) containing either 0% (CT) or 15% (TM) mealworm meal (52.4% CP, 28.0% EE and 8.8% ash as fed). Two broilers/pen were slaughtered at 53 days of age. Liver, jejunum, and caecum samples were collected and stored in RNA Later solution (Ambion) at -80°C pending analysis. Pooled samples of each treatment were analyzed for RNA-seq using Illumina NGS analyzer. Differential expression of genes (DEG) was carried out using Cuffdiff test. Fisher test corrected with Bonferroni procedure [1] was used for statistical analysis of RNA sequencing data. Significant differences were considered for p

Iba-1 immunoreactivity (Iba-1-ir) is shown in the m-PFC of sham or SNI mice (30 days after injury) following PEA (10 mg/kg, i.p.) or vehicle treatment (A). Quantitative analysis of total, or activated or hyperbranched, is shown in “B”. Data are expressed as mean ± S.E.M of 3 mice per group. * indicates significant differences compared to sham/vehicle. P

Neuropathic pain is defined as pain initiated or caused by a primary lesion or dysfunction in the nervous system. It is a devastating and difficult to manage consequence of peripheral nerve injury and has a variety of clinical symptoms. Neuropathic pain is a major health problem. It has been estimated that 70% of patients with advanced cancer and inflammatory pathologies are afflicted by chronic pain. About 95% of patients with spinal cord injuries have neuropathic pain problems. Chronic pain is debilitating and cause of depression and decreasing quality of life. Pharmacological treatment for the symptoms of painful neuropathy is difficult, because there has been limited understanding of the underlying causes and systemic levels that an effective dose can have on multiple side effects. The use of molecular methods, such as gene therapy, stem cell therapy and viral vector for delivery of biologic antinociceptive molecules, has led to a better understanding of the underlying mechanisms of the induction of intractable neuropathic pain.

Purpose. The aim of this work was to develop nanosystems for the use of zoledronic acid (ZOL) in the treatment of symptoms associated with neuropathic pain and to assess the potential antineuropathic effect and the potential targets in the spinal cord (neurons, astrocytes, microglia). Materials and methods. PEGylated liposomes containing ZOL (lipoZ) were prepared by the reverse phase evaporation technique followed by extrusion, purification and lyophilization. The effectiveness of lipoZ was evaluated in an animals model of peripheral neuropathy, spared nerve injury (SNI). In particular, we evaluated the effects of lipoZ on mechanical allodynia. Finally, morphological assessments at the dorsal horn of the spinal cord (L4-L6) were made to investigate a potential action of lipoZ on reactive gliosis associated with neuropathic pain. Results. LipoZ with mean diameter of about 241 nm and an actual loading of ZOL between about 101 ???g ZOL/mg lipids were prepared. In vivo studies showed a significant reduction of mechanical allodynia after treatment with lipoZ; the treatment with free ZOL and blank liposomes were not produced any effect. The morphological analysis of the spinal cord of neuropathic mice, after treatment with blank liposomes, showed a change in the morphology of the astrocytes, as they are hypertrophied in the dorsal horn; this hypertrophy was not observed in mice treated with lipoZ. In addition, treatment with lipoZ produced an increase of IL-10, an anti-inflammatory cytokine, in astrocytes. Conclusions. For the first time, through the use of nanotechnology, the activity of ZOL for the treatment of neuropathic pain was demonstrated in vivo.

Introduzione. L’acido zoledronico (ZOL) è il più potente inibitore dell’attività degli osteoclasti. Studi pre-clinici hanno dimostrato che ZOL, in modelli animali di dolore da metastasi ossee, riduce significativamente l’allodinia e l’iperalgesia meccanica associata con neuropatia periferica, nonché l’infiammazione. Tuttavia, la breve emivita ed il rapido accumulo di ZOL nel tessuto osseo, impediscono al farmaco di raggiungere concentrazioni farmacologicamente attive in alcuni distretti tissutali. Scopo del lavoro. Sviluppare nanosistemi che consentano l’impiego di ZOL nel trattamento dei sintomi associati al dolore neuropatico e valutarne il potenziale effetto antineuropatico ed i potenziali target a livello spinale (neuroni, astrociti, microglia). Materiali e metodi. Liposomi PEGhilati contenenti ZOL (lipoZ) sono stati preparati mediante la tecnica di evaporazione in fase inversa seguita da estrusione, purificazione e liofilizzazione. L’efficacia dei lipoZ è stata valutata in un modello murino di neuropatia periferica, la spared nerve injury (SNI). In particolare, sono stati valutati gli effetti sull’allodinia meccanica e sono state effettuate valutazioni morfologiche a livello delle corna dorsali del midollo spinale (L4-L6) al fine di investigare una potenziale azione di lipoZ nella gliosi reattiva spinale associata a dolore neuropatico. Risultati. Sono stati preparati lipoZ con dimensioni comprese tra 203 e 241 nm ed un contenuto di ZOL compreso tra circa 77 e 101 g/mg di lipidi. Studi in vivo hanno dimostrato una significativa riduzione di allodinia meccanica in seguito a trattamento con lipoZ; il trattamento con ZOL libero e liposomi bianchi non produce alcun effetto. Dall’analisi morfologica del midollo spinale dei topi neuropatici, in seguito a trattamento con liposomi bianchi, è stato osservato un cambiamento della morfologia degli astrociti, in quanto risultano ipertrofici nelle corna dorsali mentre tale ipertrofia non è stata riscontrata nei topi trattati con lipoZ. Inoltre, il trattamento con lipoZ determina un aumento di IL-10, una citochina antinfiammatoria, negli astrociti. Conclusioni. Grazie all’impiego delle nanotecnologie è stata dimostrata un’attività di ZOL nel trattamento dei sintomi del dolore neuropatico in vivo.

The potential use of micro-Raman spectroscopy for estimating the microstructural changes occurring in periodontal ligaments after orthodontic treatment was explored. An in vitro investigation on bovine ligaments was carried out in order to find the appropriate conditions for studying human cases. The results were compared with preliminary analysis from human samples.

Four bovine BAC clones (0494F01, 0069D07, 0060B06, and 0306A12) containing MUC1, as confirmed by mapping MUC1 on a RH3000 radiation hybrid panel, were hybridised on R-banded chromosomes of cattle (BTA), river buffalo (BBU), sheep (OAR) and goat (CHI). MUC1 was FISH-mapped on BTA3q13, BBU6q13, OAR1p13 and CHI3q13 and both chromosomes and chromosome bands were homoeologous confirming the high degree of chromosome homoeologies among bovids and adding more information on the pericentromeric regions of these species’ chromosomes. Indeed, MUC1 was more precisely assigned to BTA3 and assigned for the first time to BBU6, OAR1p and CHI3. Moreover, detailed and improved cytogenetic maps of BTA3, CHI3, OAR1p and BBU6 are shown and compared with HSA1.

The effects of infusing the glutamate receptor agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) on the release of dopamine (DA) has been studied in rat hippocampus and striatum in vivo. In hippocampus, AMPA (1-10 microM) produced a dose related increase in dialysate DA, but at 100 microM AMPA a sustained decrease in extracellular DA was observed. However, when samples were collected at 5-min intervals 100 microM AMPA infusion revealed a brief increase in hippocampal dialysate DA. Infusion of 100 microM AMPA and 500 microM diazoxide, which blocks AMPA receptor desensitization, led to a marked increase in extracellular DA, as did diazoxide alone, although to a lesser extent. The AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3,-dione (CNQX; 200 microM) reversed the effect of AMPA and/or diazoxide infusion on dialysate DA and when infused alone, CNQX also decreased hippocampal dialysate DA. AMPA (50-500 microM) increased striatal DA release. The effect of AMPA on extracellular DA was reversed by CNQX (200 microM). Diazoxide infusion caused a decrease in striatal DA release, and this was not affected by CNQX. These data suggest that hippocampal, but not striatal AMPA receptor desensitization may play a role in regulating DA release.

The effects of infusing N-methyl-D-aspartate (NMDA), and the specific NMDA receptor antagonist D-2-amino-5-phosphono-propionic acid (D-AP5) into rat hippocampus and striatum on extracellular dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were studied using intracerebral microdialysis. In striatum NMDA increased DA extracellularly in a concentration-dependent manner. Against a 10 microM concentration of NMDA the increase in striatal DA was opposed by D-AP5 (10 microM in all experiments), which when infused alone significantly reduced DA concentration. Infusion of NMDA altered DOPAC level in a complex manner, with 10 microM concentration causing a significant increase 2 h after infusion, while 100 microM NMDA caused a transient decrease in the metabolite. None of treatments altered striatal dialysate HVA. In hippocampus NMDA infusion decreased dialysate DA in a concentration-dependent manner, and the decrease caused by 10 microM NMDA was reversed by D-AP5. When given alone the antagonist was without effect. NMDA infusion elevated hippocampal dialysate DOPAC and HVA, while HVA was decreased following D-AP5 infusion. These data indicate that DA release is regionally controlled by excitatory amino acids, but in differential manner.

The present study has been carried out to determine if glycine, an allosteric modulator of NMDA receptor, is involved in the vascular effect induced by the activation of the CNS NMDA receptors.Icv NMDA (from 0.01 to 1µg/rat in the 3rd ventricle) caused a significant increase in arterial blood pressure in conscious freely moving rats. Moreover, the hypertension was associated with behavioural modifications (jumping, rearing, teething and running). Glycine pretreatment (1 and 10µg/raticv), significantly increased the NMDA hypertension. Glycine alone did not cause any arterial blood pressure modification while it induced a slight sedation. HA-966 (an antagonist of the glycine site on NMDA receptor) administration (1-10µg/raticv 5 min before glycine) significantly antagonized the glycine effects on NMDA hypertension.Alone HA-966 neither modified arterial blood pressure nor antagonized NMDA hypertension. In conclusion, our investigations confirm NMDA receptor involvement in cardiovascular function and they demonstrate thatin vivo glycine positively modulates NMDA receptors.

Left ventricular hypertrophy (LVH) is a frequent finding in Friedreich’s ataxia (FRDA). In previous studies treatment with idebenone, a synthetic analogue of coenzyme Q10, has been associated with a substantial decrease in myocardial hypertrophy, despite great variability in cardiac responsiveness among patients. Here we present the results of a retrospective analysis of a cohort of 35 patients (20 with LVH, 15 without LVH) with confirmed molecular diagnosis of FRDA, treated with idebenone 5 mg/kg/day for up to five years. At the end of the study, we found an increase of interventricular septum and posterior wall thickness in the group without LVH before treatment and no change in the group with LVH before treatment. The neurological picture of the disease significantly deteriorated with time in both groups.

Metabotropic glutamate receptors (mGluRs) are a family of G-protein-coupled receptors which play an important role in the modulation of nociception transmission and plasticity [1,2]. In this review we will consider the control of supraspinal nociception by mGluR ligands in several animal models of pain through behavioural and biochemical approaches. More specifically, we will focus our attention on the mGluRs of the midbrain periaqueductal gray (PAG), which has been recognized as an antinociceptive area since 1969. The multiplicity of responses associated with mGluR stimulation is complicated by the localization of these receptors on a variety of pre- and postsynaptic elements of either glutamate, GABA and non-GABA containing neurons that characterize the PAG circuitry. In particular, excitatory-postsynaptic group I mGlu1/5 subtype receptors produce a preferential activation of descending excitatory antinociceptive pathways at the PAG level, while group III mGlu8 receptors modulate the release of glutamate and GABA conversely. Indeed, selective stimulation of mGlu8 receptors generates an increase in glutamate and a decrease in γ-aminobutyric acid (GABA) extracellular levels. These data, together with the evidence that these receptors are present presynaptically on both symmetrical and asymmetrical synapses, justify that their stimulation relieves hyperalgesia in inflammatory pain. Unlike mGlu8, the mGlu7 receptors in the PAG inhibit antinociception via negative modulation of glutamate release, as they seem expressed mainly on asymmetrical synapses. In this review we aim to illustrate the role of mGluRs in controlling nociceptive processes, as well as their interaction with other neurotransmitters within the PAG, in the hope that further findings in this field will pave the way for the development of useful new agents in pain therapy.

Metabotropic glutamate (mGlu) and cannabinoid receptors are G-protein coupled receptors which have shown synaptic co-operation through small lipid messengers in the central nervous system (CNS). A functional interaction between these two receptor families could have a relevant potential in the treatment of CNS disorders, including chronic pain. Indeed, both mGlu and cannabinoid receptors play a crucial role in the neurobiology of pain and their simultaneous manipulation could lead to novel strategies in pain management. In particular, as both mGlu and cannabinoid receptors have been found in the periaqueductal gray (PAG), a crucial station in the pain modulatory system, these receptors could be a substrate for producing analgesia at this level. In this review we aim to briefly illustrate the role of mGlu and can-nabinoid receptors in controlling nociceptive processes, some points of convergence, and their functional interaction in pain processing. Further insights into this functional linkage between the mGlu and cannabinoid receptors could pave the way to a new strategy for pain relief, such as a drug cocktail acting on cannabinoid/metabotropic glutamate receptors.

OBJECTIVES—To investigate right ventricular diastolic function in systemic sclerosis (SSc) and its relation to clinical features of the disease. METHODS—Seventy seven unselected SSc patients and 33 healthy subjects were submitted to echocardiography and echo Doppler study to assess left and right systolic as well diastolic function and to estimate maximal arterial systolic pulmonary pressure (PAP). In addition, the patients were investigated to define the SSc subset and the extent of skin and internal organ involvement. RESULTS—An abnormal right ventricular filling, as expressed by an inverted tricuspidal (Tr) E/A ratio (Tr E/A ratio 30 mm Hg. Twenty resulted to have an inverted mitral (Mit) E/A ratio (Mit E/A ratio

We have investigated the effects of infusing the excitatory amino acid agonist alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) on extracellular levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in rat striatum using in vivo microdialysis. AMPA (50-500 microM) caused a concentration-dependent increase in extracellular 5-HT, while having the converse effect on 5-HIAA. At the highest agonist dose the decrease in dialysate 5-HIAA was followed by a significant increase in this metabolite. Two hundred micromolar 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a competitive non-NMDA glutamate receptor antagonist, reversed the effects of a 100 microM AMPA on dialysate 5-HT and 5-HIAA. Co-infusion of AMPA with tetrodotoxin (TTX) abolished the effects of 100 microM AMPA, but only partially reversed the effect of 500 microM AMPA on 5-HT release. We have also investigated whether AMPA receptor desensitization, a well documented event, plays a role in AMPA receptor modulation of striatal 5-HT release. Diazoxide (500 microM), a drug which prevents AMPA receptor desensitization, failed to augment the effect of 100 microM AMPA on 5-HT release. Diazoxide alone significantly decreased 5-HT release, as did the drug cromakalim (100 microM), probably as a result of their common action as activators of ATP-dependent K+ channels. It is concluded that AMPA receptors play a role in regulating both 5-HT release and metabolism in rat striatum. However, AMPA receptor desensitization does not appear to play a role in this process in this structure.

Clinical treatment of recurrent spontaneous abortion (RSA) is still a matter of debate due to the absence of an univocal definition of the term. As a consequence of the reproductive history of the couple, there is still uncertainty regarding the moment when the problem of recurrent abortion arises and this prevents the start of diagnostic evaluation and therapy. In addition to a critical review of the literature, the aim of this study was to evaluate whether two successive abortions with the same partner are sufficient to suggest that the couple should undergo diagnostic test, or if it would be more sensible to wait for other reproductive failures. The study was performed in 50 couples suffering from recurrent abortion who attended the Laboratory of Cytogenetics in the Department of Animal Biology at Turin University for caryotyping in order to exclude the presence of chromosomal aberrations. Interviewed by telephone, out of 50 couples 41 presented the necessary requisites for being included in the study. Follow-up ranged between a maximum of 8.5 years and a minimum of 1 year (mean of 4.7 years). From the data collected it emerged that the probable cause of RSA was identified in 21 out of 41 couples enrolled in the study group (51.2 per cent). In the remaining 20 couples tests were within normal ranges. In all diagnosed cases the reproductive problem was identified with one or more alterations present in women. Among the hypothesized cause of RSA, uterine abnormalities were the most frequent (19.5 per cent), followed by immunological problems (17.1 per cent), etiologic factors of hormonal origin (12.2 per cent), one single case of genital infection (2.4 per cent), one balanced chromosomal translocation (2.4 per cent) and at last only one case of cervical incompetence of (2.4 per cent). The diagnosis was determined effectively in 85.7 per cent of couples. Of 20 couples who had not shown any abnormalities, 80 per cent had had a healthy child without any abortions and with the same partner. In conclusion, diagnostic tests performed finally identified the cause of RSA in 43.9 per cent of the couples who completed the procedure; vice versa, 39.0 per cent of couples solved the problem without the need for diagnostic tests; finally, the remaining 18.1 per cent were unable to carry pregnancy to term. By comparing our results to those reported by other authors, we believe that the probability of identifying the cause of RSA and curing it is sufficiently high to justify the start of the diagnostic evaluation of the problem as early as the second abortion in view of the stress on the couple produced by repeated reproductive failures.

Strong evidence implicates glutamate as an excitatory neurotransmitter in the central nervous system. In the present study we have investigated the effects of different concentrations of the excitatory amino acid agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid on release of 5-hydroxytryptamine in rat hippocampus using in vivo microdialysis. Infusion of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid at 1 microM led to an increase in dialysate 5-hydroxytryptamine. In contrast 100 microM alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid decreased extracellular 5-hydroxytryptamine, collected in 30 min samples, and this decrease was sustained for several hours. alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor desensitization is well documented in vitro, and is reversed by the drug diazoxide. We therefore studied the possibility that this was occurring in hippocampus in vivo. Collection of dialysates at 5 min time intervals revealed a brief increase in dialysate 5-hydroxytryptamine in response to 100 microM alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, although basal level of 5-hydroxytryptamine was below the level of detection. When 100 microM agonist was co-infused with 500 microM diazoxide, a substantial and prolonged increase in dialysate 5-hydroxytryptamine was seen. Diazoxide alone was observed to cause an increase in extracellular 5-hydroxytryptamine. Diazoxide is known to active ATP-dependent K+ channels, however, cromakalim (100 microM), an activator of ATP-dependent K+ channels, reduced hippocampal 5-hydroxytryptamine release, suggesting that the effect of diazoxide is not the result of such an action.(ABSTRACT TRUNCATED AT 250 WORDS)

The activity of nucleolar organizer regions (Ag-NORs) and the frequency of NOR associations in chromosomes of phytohemagglutinin-stimulated lymphocytes from 12 patients with laryngeal carcinoma and 12 healthy subjects were studied using the gelatine silver staining technique. This study was undertaken to examine whether any disease associated changes occur in NOR activity. A lower mean number of Ag-NORs per metaphase (t test, 0.05p0.02) was found in patients compared to controls. This difference was not due to any specific group of acrocentric chromosomes (D or G). The mean number of NOR associations per metaphase was also found to be markedly lower (t test, 0.01p0.001) in patients than in controls. This difference was principally due to the significant decrease in the associations between 2 chromosomes (t test, 0.02p0.01), and in particular to the decrease in the D-G type associations (t test, 0.05p0.02). These findings are discussed in relation to existing data on the nucleolar activity of lymphocytes in a variety of solid tumours and leukemias.

Eighteen patients with isolated stenosis of left anterior descending artery, were randomly given 0.2 mg of nifedipine (Group II) or its solvent (Group I) via balloon catheter positioned across the lesion immediately prior balloon occlusion. Peak velocity of early (E peak) and late (A peak) filling, velocity flow integral at early (E area) and late (A area) filling and their ratios (by echo-Doppler) and heart rate, mean aortic and wedge (W) pressures were measured at baseline, 15 and 30 s during balloon occlusion and 10 min after balloon deflation. In Group I we observed a significant decrease in either E peak at 15 and 30 s (-24.7%, -29.3% respectively) and E area (-32.8%, -40.0% respectively) with a non significant increase in both A peak and A area. Accordingly, either E/A peak ratio and E/A area ratio decreased significantly. In Group II no significant changes were observed in the echo-Doppler parameters of left ventricular filling. Wedge pressure also significantly increased in Group I at 15 and 30 s (68.7% and 97.9% respectively), while a significant increase in Group II occurred only at 30 s (32.5%). Heart rate significantly increased only in Group I at 15 and 30 s (10.3% and 11% respectively), while aortic pressure remained unchanged in both groups. Thus, nifedipine given intracoronary in the post-stenotic area just before balloon occlusion prevents left ventricular filling dynamic alteration by preserving early filling.

Cardiac involvement was noninvasively evaluated in 75 consecutive patients with systemic lupus erythematosus (SLE) by two-dimensional and Doppler echocardiography. In 50/75 patients anticardiolipin antibodies (aCL) were also investigated. Major endocardial damage, characterized by the simultaneous presence of both anatomical and functional valvular involvement (AFVI), was observed in three patients with valvular vegetations and in five patients with combined valvular stenosis and/or regurgitation. Nine patients showed only an anatomic valvular involvement (AVI), expressed by a thickening of one or more valvular leaflets, without echo-Doppler findings of valvular dysfunction. Occurrence of major valvular involvement appears to be correlated with both longer disease duration (9.8 +/- 5.6 yrs in AFVI group vs 5.7 +/- 5.6 yrs in the remaining SLE patients; p0.001) and IgG aCL (chi-square = 5.546; p0.05). Left ventricular systolic function, evaluated by two-dimensional echocardiographic ejection fraction, was preserved in all patients (EF: 60 +/- 5%). Left ventricular diastolic function, as expressed by echo-Doppler transmitral flow indices of left ventricular filling, was subclinically impaired in 23 patients: only disease duration was significantly longer in these patients (7.7 +/- 5.9 yrs vs 4.9 +/- 4.8 yrs; p0.05). Our study demonstrated that cardiac involvement is quite frequent in SLE patients: the disease duration affects both endocardial and myocardial involvement; the anticardiolipin antibodies appear to be related to endocardial but not to myocardial damage.

34 patients with ventricular dysfunction (18 in NYHA class II and 16 in NYHA class III heart failure) whose clinical status was stabilized by diuretics and systemic vasodilators, entered a randomized trial to compare the effects of short-term oral digoxin and active placebo on left ventricular diastolic function, non invasively evaluated by echo-Doppler transmitral left ventricular filling flow. At baseline patients were subdivided by reversal--the ratio of peak early (E) and late (A) transmitral filling velocities--E/A1 (group I) or normal--E/Aor = 1 (group II) echo-Doppler E/A ratio; group II exhibited a shorter deceleration time (125 +/- 20 ms vs 198 +/- 38 ms, p0.05) and isovolumic relaxation time (64 +/- 15 ms vs 93 +/- 10 ms; p0.05) as well as a higher peak E velocity (85 +/- 28 cm/s vs 54 +/- 20 cm/s; p0.05), ("restrictive" left ventricular filling pattern). After 4 weeks, no changes in all echo-Doppler parameters were noted in group I in response to either oral digoxin or active placebo. Clinical amelioration (defined as reduction by at least one functional class) was observed in 3 patients after digoxin.(ABSTRACT TRUNCATED AT 250 WORDS)

Thirty patients undergoing epirubicin therapy for primary lung cancer were studied by echocardiography and Doppler echocardiography. 2 D ejection fraction (EF) and Doppler left ventricular filling parameters (peak E, peak A, E/A ratio) were calculated before and after the completion of therapy. No differences in the mean values of these parameters were observed. However, 6 out of 30 patients (20%) showed left ventricular filling abnormalities; in 2 of them a slight reduction of EF was also noted. These abnormalities seem to be dose related. A longer term prospective study will be required to evaluate whether these findings are irreversible and to establish the clinical implications of our observations.