Placebo analgesia and the heart

Placebo-activated endogenous opioids act on pain mechanisms inducing analgesia, as well as on the respiratory centers inducing respiratory depression. Here, we show that placebo analgesia is accompanied by a reduced beta-adrenergic activity of the heart. We measured heart rate during placebo-induced expectation of analgesia, both in the clinical and the laboratory setting. In the clinical setting, we found that the placebo analgesic response to an electrical noxious stimulus was accompanied by a reduced heart rate response. In order to investigate this effect from a pharmacological viewpoint, we reproduced the same effect in the laboratory setting by using experimental ischemic arm pain. We found that the opioid antagonist naloxone completely antagonized both placebo analgesia and the concomitant reduced heart rate response, whereas the beta-blocker propranolol antagonized the placebo heart rate reduction, but not placebo analgesia. By contrast, both placebo responses were present during muscarinic blockade with atropine, indicating no involvement of the parasympathetic system. In order to better understand the effects of naloxone and propranolol, we performed a spectral analysis of the heart rate variability for the identification of the sympathetic and parasympathetic components, and found that the beta-adrenergic low frequency (0.15 Hz) spectral component was reduced during placebo analgesia, an effect that was reversed by naloxone. These findings indicate that placebo analgesia is accompanied by a complex cascade of events which affect the cardiovascular system.     

Risk of Poisoning from Garden Plants: Misidentification between Laurel and Cherry Laurel

The misidentification between edible and poisonous plants is an increasing problem because of the new trend to collect wild plants, especially by amateur collectors who do not have the botanical skills to distinguish between edible and toxic species. Moreover, morphologically similar species are sometimes responsible for accidental contamination or used in the intentional adulteration of products for human and animal consumption. Laurus nobilis L. (laurel) and Prunus laurocerasus L. (cherry laurel) are typical ornamental shrubs of the Mediterranean region. Laurel is considered a non-toxic plant, widely used as flavorings. Conversely, cherry laurel leaves, morphologically similar to those of laurel, contain toxic cyanogenic glycosides. Considering this, the aim of this study was to carry out an in-depth evaluation of laurel and cherry laurel leaves by using light and scanning electron microscopy coupled with three step phytochemical analyses (qualitative and quantitative colorimetric assays and liquid chromatography). This allowed to highlight the distinguishing features of plant species investigated features such as the venation pattern, presence/absence of nectaries, calcium oxalate crystals, secretory idioblasts, and cyanogenic glycosides. Concluding, this multidisciplinary approach can be useful for the identification of plants but also fragments or pruning residues containing cyanogenic glycosides, in quality control tests, intoxications, and criminal cases.     

Extra-Nodal Lymphomas of the Head and Neck and Oral Cavity: A Retrospective Study

Disease Overview: Lymphomas, both Hodgkin’s and non-Hodgkin’s lymphomas, are one of the most common cancers in the head and neck area. The extra-nodal variant of lymphoma is rare, but it is the most common non-Hodgkin’s lymphoma (ENHL). Furthermore, it is difficult to diagnose due to its non-specific clinical and radiological features, which can mimic other benign or malignant clinical manifestations. The study: This retrospective study involved 72 patients affected by head and neck ENHL in the period between 2003 and 2017. All patients underwent a diagnostic-therapeutic procedure according to the guidelines, and a 5-year follow-up. Based on the location of the swelling at the time of diagnosis, patients were divided into two groups: oral and non-oral ENHLs. Statistical analysis was performed using Kaplan–Meier analysis with the log-rank test. In addition, Fisher’s exact test was applied to the two groups to evaluate and compare variances (the acceptable significance level was set at p < 0.05). Conclusion: ENHL with oral localization is much more aggressive than ENHL with non-oral localization, with a death rate of 40% (versus 4.76 for the non-oral one). In fact, between the two groups, there is a statistically significant difference in mortality, with a p-value of 0.0001 and 0.0002, respectively.     

Recent Advances in the Neuroprotective Properties of Ferulic Acid in Alzheimer’s Disease: A Narrative Review

Alzheimer’s disease (AD) is a progressive degenerative disorder of the central nervous system, characterized by neuroinflammation, neurotransmitter deficits, and neurodegeneration, which finally leads to neuronal death. Emerging evidence highlighted that hyperglycemia and brain insulin resistance represent risk factors for AD development, thus suggesting the existence of an additional AD form, associated with glucose metabolism impairment, named type 3 diabetes. Owing to the limited pharmacological options, novel strategies, especially dietary approaches based on the consumption of polyphenols, have been addressed to prevent or, at least, slow down AD progression. Among polyphenols, ferulic acid is a hydroxycinnamic acid derivative, widely distributed in nature, especially in cereal bran and fruits, and known to be endowed with many bioactivities, especially antioxidant, anti-inflammatory and antidiabetic, thus suggesting it could be exploited as a possible novel neuroprotective strategy. Considering the importance of ferulic acid as a bioactive molecule and its widespread distribution in foods and medicinal plants, the aim of the present narrative review is to provide an overview on the existing preclinical and clinical evidence about the neuroprotective properties and mechanisms of action of ferulic acid, also focusing on its ability to modulate glucose homeostasis, in order to support a further therapeutic interest for AD and type 3 diabetes.     

The Performance of Upper Limb (PUL) module in limb-girdle muscular dystrophy

Limb-girdle muscular dystrophy (LGMD) is a genetic muscle disorder causing weakness and wasting of the proximal limb musculature. When ambulation is lost, the attention must be shifted to the upper limb muscles’ function. We studied the upper limb muscle strength and the corresponding function in 15 LGMDR1/LGMD2A and 13 LGMDR2/LGMD2B, through the Performance of Upper Limb scale and the MRC score of upper limbs. The proximal item K and the distal items N and R were lower in LGMD2B/R2. The mean MRC score of all the muscles involved linearly correlated (r2 = 0.922) for item K in LGMD2B/R2. The functional worsening paralleled the muscles weakness in LGMD2B/R2. By contrast, at proximal level the function of LGMD2A/R1 was preserved despite muscle weakness was present, presumably due to compensatory strategies. Sometimes the combination of parameters might be more informative than considering them separately. PUL scale and MRC might be interesting outcome measures in non-ambulant patients.Key words: Performance of Upper Limb (PUL version 1.2) scale, limb-girdle muscular dystrophy, LGMD2A/R1, LGMD2B/R2, MRC score     

A fluorescent curcumin-based Zn(II)-complex reactivates mutant (R175H and R273H) p53 in cancer cells

Background

Mutations of the p53 oncosuppressor gene are amongst the most frequent aberration seen in human cancer. Some mutant (mt) p53 proteins are prone to loss of Zn(II) ion that is bound to the wild-type (wt) core, promoting protein aggregation and therefore unfolding. Misfolded p53 protein conformation impairs wtp53-DNA binding and transactivation activities, favouring tumor growth and resistance to antitumor therapies. Screening studies, devoted to identify small molecules that reactivate mtp53, represent therefore an attractive anti-cancer therapeutic strategy. Here we tested a novel fluorescent curcumin-based Zn(II)-complex (Zn-curc) to evaluate its effect on mtp53 reactivation in cancer cells.

Methods

P53 protein conformation was examined after Zn-curc treatment by immunoprecipitation and immunofluorescence assays, using conformation-specific antibodies. The mtp53 reactivation was evaluated by chromatin-immunoprecipitation (ChIP) and semi-quantitative RT-PCR analyses of wild-type p53 target genes. The intratumoral Zn-curc localization was evaluated by immunofluorescence analysis of glioblastoma tissues of an ortothopic mice model.

Results

The Zn-curc complex induced conformational change in p53-R175H and -R273H mutant proteins, two of the most common p53 mutations. Zn-curc treatment restored wtp53-DNA binding and transactivation functions and induced apoptotic cell death. In vivo studies showed that the Zn-curc complex reached glioblastoma tissues of an ortothopic mice model, highlighting its ability to crossed the blood-tumor barrier.

Conclusions

Our results demonstrate that Zn-curc complex may reactivate specific mtp53 proteins and that may cross the blood-tumor barrier, becoming a promising compound for the development of drugs to halt tumor growth.     

Adriamycin-induced histamine release from heart tissue in vitro

 It has been proven that the anthracyclines induce an important, noncytotoxic histamine release from rat peritoneal mast cells. As mast cells derived from different tissues exhibit marked heterogeneity, the effect of Adriamycin in comparison with other antineoplastic agents was tested on fragments of the right heart auricle, which contain a great number of mast cells. In this experimental model, Adriamycin induced a dose-dependent histamine release that was significantly limited by the antiexocytotic drug sodium cromoglycate. The antineoplastic agents cisplatin and 5-fluorouracil, in contrast, did not provoke any comparable histamine release. In the formulation employed in clinical settings, paclitaxel was also capable of inducing a histamine release comparable with that of Adriamycin; the exocytotic activity, however, was also evident when the tissue fragments were treated with Cremophor EL alone, without the addition of paclitaxel, whereas treatment of samples with paclitaxel dissolved in ethanol did not induce any releasing action. These data thus suggest that the secretory activity should be ascribed to the solvent Cremophor EL and not to paclitaxel. The release of histamine induced by paclitaxel in Cremophor EL/ethanol was also limited by sodium cromoglycate. These results again indicate that histamine release from mast cells derived not only from the peritoneal cavity but also from the cardiac tissue could play a role in the cardiotoxicity of anthracyclines and of paclitaxel in the clinically employed formulation. Received: 18 August 1996 / Accepted: 22 December 1996     

Physical Properties of an Eco-Sustainable,Form-Stable Phase Change Material Included in Aerial-Lime-Based Mortar Intended for Different Climates

The aim of this experimental investigation was to produce a form-stable phase change material (PCM) able to reduce the need for nonrenewable energy resources required for the heating/cooling of buildings located in regions characterized by different climatic conditions. The innovative PCM must also be sustainable and must be produced according to the principles of the circular economy. To achieve such ambitious goals, a form-stable, sustainable PCM was produced through vacuum impregnation. The form-stable PCM was produced starting from a low-toxicity, low-flammability polyethylene glycol of medium molecular weight (PEG 800), which was included in porous stone granules obtained as waste products of the cutting/processing of local (Lecce) stone. The thermal properties and thermal stability of PEG 800 and of its PCM-composite were evaluated by employing differential scanning calorimetry (DSC) and thermo-gravimetric analysis (TGA). The appropriate parameters to perform the impregnation procedure were identified through rheological and calorimetric analyses. A simple leakage test was performed to assess if the PEG polymer can leak from the stone flakes. Finally, the new PCM was added as an aggregate in aerial-lime-based mortars, and the mortar’s properties were analyzed in fresh (workability) and hardened (flexural and compressive strength and thermal characteristics) states for potential applications, particularly in ancient buildings.