Plasma,red blood cells phospholipids and clinical evaluation after long chain omega-3 supplementation in children with attention deficit hyperactivity disorder (ADHD)

Omega-3 and omega-6 long-chain polyunsaturated fatty acids (LCPUFAs), are crucial to brain development and function. Increasing evidence indicates that deficiencies or metabolic imbalances of these fatty acids might be associated with childhood developmental and psychiatric disorders including attention-deficit/hyperactivity disorder (ADHD). Omega-3 are often lacking on modern diets. Moreover preliminary evidences suggest that supplementation with omega-3 LCPUFAs, might help in the management of the ADHD linked behavioural and learning difficulties. However, few studies published to date have involved different populations, study designs, treatments and outcome results. Thus, further researches are required to assess the durability of the treatment effects, to determine optimal composition and dosages of the supplement and to develop reliable ways to identify patients that might have some benefits from this kind of treatment, also because the study of LCPUFAs and their metabolism might offer new approaches to the early identification and management of ADHD.

In this paper, we provide new insight on the lipid pattern in plasma and red blood cells (RBC) phospholipids, together with evaluation of the arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio which seems to correlate with the improvement of the patients both from a biochemical and clinical point of view.     

Valproic acid activity in androgen-sensitive and -insensitive human prostate cancer cells

Histone deacetylase (HDAC) inhibitors are currently undergoing clinical trials in cancer patients on the basis of their effect on proliferation, differentiation and apoptosis demonstrated in vitro. The goal of this study was to assess the effects of an HDAC inhibitor, valproic acid (VA), on proliferation, androgen-sensitivity, androgen receptor levels and E-cadherin (E-cad) expression in human prostate cancer cells. The effects of VA were evaluated in androgen-sensitive, LNCaP and -insensitive PC-3 human prostate cancer cell lines. Proliferation was assayed by cell counts and protein expression by Western blot analysis. Morphological changes were analysed under an inverted phase contrast microscope. High VA concentrations (1-25 mM) induced a very strong reduction in cell numbers ( approximately 90% with respect to control) of the two cell lines due to drug cytotoxicity. A low concentration (0.45 mM VA) slightly reduced (14%) LNCaP cell proliferation and abolished the response to androgen. In the PC-3 cells, the same concentration of VA had a more pronounced (40%) inhibitory effect and induced a response to dihydrotestosterone in terms of an enhancement in cell growth. These events were associated with morphological changes, an absence of cytotoxicity, an increase in androgen receptor levels, and, in PC-3 cells, an enhancement in E-cad expression which may be ascribed to VA differentiative action. Our findings, obtained with a VA dose (0.45 mM), which is consistent with plasma concentrations reached under oral administration of therapeutical doses in patients treated for different diseases, suggest that VA might have clinical value in prostate cancer therapy in androgen-sensitive and -insensitive tumors.     

The electroretinogram of the little owl (Athene noctua)

Electroretinographic responses (ERGs) have been recorded from the cornea of the little owl (Athene noctua) in response to single light flashes and to alternating sinusoidal gratings (pattern) at different levels of light adaptation. Both flash- and pattern-evoked ERGs show scotopic as well as photopic components. The pattern evoked ERG is spatially tuned with tuning functions which shift towards lower frequencies by reducing the mean luminance. The retinal acuity is about 6c/deg at 2.3 log cd/m² and decreases progressively by reducing the mean luminance. No pattern ERG can be recorded beyond −6. 7 log cd/m² at any spatial frequency. The pattern ERG amplitude decreases progressively by reducing the contrast. The extrapolated contrast threshold is about 1%. Acuity and contrast sensitivity ERG values are in the range of those obtained by operant techniques in other species with duplex retinae such as owls and cats.     

Fos-related protein expression in the midline paraventricular nucleus of the rat thalamus: basal oscillation and relationship with limbic efferents

The expression of Fos-related protein, encoded by the proto-oncogene c-fos, was investigated by means of immunohistochemistry in the paraventricular nucleus of the thalamic midline (PV) during nighttime and daytime in rats entrained to a 12-h light/12-h dark cycle. In the first step of this study the animal's physiological state preceding perfusion was monitored with electroencephalographic recording. It was thus detected that the PV contained a considerable number of Fos-like-immunostained neurons during the hours of darkness, when the rats had been awake, and that the number of Fos-like-immunoreactive neurons was significantly lower during the hours of light, after a period of sleep. In the second step of this study Fos immunohistochemistry was combined with the retrograde transport of a gold-labeled tracer injected either in the amygdala or in the nucleus accumbens. This strategy enabled us to determine that in the rats perfused during nighttime Fos-related protein was spontaneously induced in PV cells projecting to these targets, with a significant prevalence of neurons projecting to the amygdala in the anterior portion of the PV and of neurons projecting to the nucleus accumbens in the posterior part of the nucleus. In addition, a significant reduction of Fos-like-immunoreactive cells was detected in the PV ipsilaterally to the injection, indicating that tracer administration and axonal transport may interfere with c-fos expression in neurons. Altogether the present data indicate that Fos-related protein expression undergoes a marked oscillation in the PV during 24 h in basal conditions, and that c-fos is induced in the PV relay neuronal subsets when the animal is awake. This study suggests that the thalamic midline represents a site of circadian changes in neuronal genomic expression and that this information is conveyed to limbic and limbic-related structures.On leave from the Department of Anatomy, Hunan Medical University, Changsha, Hunan, People's Republic of China     

Frailties and critical issues in neuromuscular diseases highlighted by SARS-CoV-2 pandemic: how many patients are still “invisible”?

Almost 90% of neuromuscular diseases (NMDs) are classified as rare diseases, defined as conditions affecting less than 5 individuals in 10.000 (0.05%). Their rarity and diversity pose specific challenges for healthcare and research. Epidemiological data on NMDs are often lacking and incomplete. The COVID-19 pandemic has further highlighted the management difficulties of NMDs patients and the necessity to continue the program of implementation of standard of care. This article summarizes the Italian experience during pandemic.Key words: COVID-19 pandemic, neuromuscular diseases     

Association of Helicobacter pylori infection with ischemic stroke of non-cardiac origin: the BAT.MA.N. project study

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) infection has been associated with several vascular obstructive disorders. The infection induces the production of proinflammatory cytokines that could increase platelet aggregates in circulation. The aim of this case-controlled study was to evaluate the prevalence of H. pylori infection in patients with acute ischemic stroke not related to cardiac causes. METHODOLOGY: A group of 80 consecutive patients (58 males, age range: 49-65 years) with acute ischemic stroke was studied. All patients received a cranial CT and/or brain magnetic resonance imaging scan, extracranial vessel duplex ultrasonography, and transthoracic echocardiography. H. pylori infection was diagnosed by means of both 13C urea breath test and IgG antibodies to H. pylori. A group of 320 blood donors (232 males and 88 females, age range: 49-65 years) matched for sex and age served as controls. Among the patients, we investigated the presence of hypertension, cholesterol and glucose levels in serum, fibrinogen in plasma and the smoking habit. RESULTS: The presence of H. pylori infection was higher in patients than in controls: 64/80 (80%) versus 190/320 (59.4%) (P < 0.001); when analyzed for sex in 45/58 (77.5%) among male patients and in 139/232 (59.9%) among controls (P < 0.05); of the females 19 out of 22 (86.3%) patients were infected at variance with only 51/88 (57.9%) of the controls (P < 0.05). Classical risk factors for stroke did not differ among patients with and without H. pylori infection. H. pylori infection was not differently associated with current smoking, serum total cholesterol and glucose levels, fibrinogen value in plasma and hypertension when compared to the H. pylori-negative status. CONCLUSIONS: H. pylori infection appears to be significantly more frequent in middle-aged patients with acute ischemic stroke than in controls.     

Leuprorelin acetate affects adhesion molecule expression in human prostate cancer cells

Multidrug resistance is the most predominant phenomenon leading to chemotherapy treatment failure in breast cancer patients. Despite many studies having suggested that overexpression of epidermal growth factor receptor (EGFR) is a potent predictor of malignancy in cancers, systematic research of EGFR in multidrug resistant (MDR) breast cancer cells is lacking. In order to clarify the role of EGFR in MDR breast cancer cells, MCF7/Adr expressing relatively higher EGFR, and its parental cell line MCF7 expressing relatively lower EGFR, were chosen for this study. Knockdown of EGFR by siRNA in MCF7/Adr cells showed that EGFR siRNA inhibits cell migration, invasion and proliferation in vitro; converse effects were observed in MCF7 cells transfected with pcDNA3.0-EGFR plasmid. Moreover, we found that EGFR upregulated migration and invasion via EMMPRIN, MMP2 and MMP9 in addition to promoting cell cycle passage via elevation of cyclin D1 and CDK4 in MDR breast cancer cells. Interestingly, MCF7/Adr cells not expressing EGFR showed significant decrease of P-glycoprotein (P-gp) and ABCG2 expression levels, and became more sensitive to treatment of adriamycin (ADR) and paclitaxel (Taxol); the above results indicated that MDR of cancer cells is related to S-phase arrest. In conclusion, EGFR is an important factor enhancing the malignancy of MDR breast cancer cells, partially, inducing MDR. Anti-EGFR therapy may improve outcome in chemorefractory breast cancer patients.     

Proinflammatory stimuli are needed for induction of microglial cell-mediated AbetaPP_{244-C} and Abeta-neurotoxicity in hippocampal cultures

Amyloid-beta plaques and neurodegeneration are hallmarks of Alzheimer's disease, where glial cells are responsible for sustained neuroinflammation. Here we show that hippocampal-microglia co-cultures exposed to proinflammatory mediators, amyloid-beta- and amyloid-beta protein precursor construct-conjugated beads increased their production of nitrites. In contrast, inflammation was unable to significantly induce cell death by itself, whereas inflammation plus amyloid-beta or amyloid-beta protein precursor induced a significant increment of cell death and a 6-fold increase of production of Interleukin 1beta. Those effects were not observed in the absence of microglia or when hippocampal cells were co-cultured with microglia for one day. In contrast, a 2-fold increase of transforming growth factor beta1 was observed in hippocampal cultures exposed to inflammatory stimuli for 4 days, whereas induction of transforming growth factor beta1 by inflammation plus amyloid-beta and amyloid-beta protein precursor was nearly abolished by microglia. Our results indicate that neurotoxicity induced by amyloid-beta or amyloid-beta protein precursor was a slow process depending on activated microglia and additional stimuli. The observed cytotoxicity could be consequence of a vicious cycle in which elevated concentrations of Interleukin 1beta and radical species along with decreased secretion of neuroprotective cytokines such as transforming growth factor beta1 support persistent activation of glial cells and cell damage.