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Cannabidiol (CBD) is the second cannabinoid, in order of importance after Δ9-tetrahydrocannabinol (THC), from Cannabis sativa. Unlike THC, CBD does not cause psychotomimetic effects, and although these compounds have the same chemical formula, their pharmacological characteristics are not equivalent. Preclinical studies suggest that CBD has anti-inflammatory, analgesic, anxiolytic, antiemetic, anticonvulsant, and antipsychotic properties and influences the sleep–wake cycle. The evaluation of effects on spontaneous motor activity is crucial in experimental pharmacology, and the careful measurement of laboratory animal movement is an established method to recognize the effects of stimulant and depressant drugs. The potential influence of CBD on locomotor activity has been investigated through numerous in vivo experiments. However, there is no clear picture of the impact of CBD on these issues, even though it is administered alone for medical uses and sold with THC as a drug for pain caused by muscle spasms in multiple sclerosis, and it was recently licensed as a drug for severe forms of infantile epilepsy. On this basis, with the aim of developing deeper knowledge of this issue, scientific data on CBD’s influence on locomotor activity are discussed here. We conducted research using PubMed, Scopus, Google Scholar, and a search engine for literature between January 2009 and December 2021 on life sciences and biomedical topics using the keywords “motor activity”, “locomotor activity”, and “locomotion” in combination with “cannabidiol”. In this article, we discuss findings describing the effects on locomotor activity of the CBD precursor cannabidiolic acid and of CBD alone or in combination with THC, together with the effects of CBD on locomotor modifications induced by diseases and on locomotor changes induced by other substances.

It is estimated that 10–50% of interventions can generate persistent post-surgical pain. Chronic post-mastectomy pain is a condition persisting for at least three months after surgery. It has been shown that physical activity in the cancer patient allows the improvement of the pain symptom. The aim of this study was to evaluate the effects of physical activity on the intensity and interference of chronic pain in the quality of life of women underwent mastectomy needed for breast cancer removal. The secondary objective was to measure the effects of physical activity on inflammatory and oxidative markers in the same population. A Numeric Rating Scale (NRS) was used to assess pain intensity, and Brief Inventory Pain (BIP) was used for assessing interference of pain in quality of life. Physical activity was measured with the International Physical Activity Questionnaire (IPAQ). Inflammatory mediators such as interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, c-reactive protein (CRP), and biomarkers of oxidative stress malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) were evaluated in the blood of patients. All the evaluations were performed after three and six months after surgery. Results showed that adequate physical activity can diminish intensity and interference of pain and that these effects are associated with a reduction of blood biomarkers of inflammation.

Dietary supplements are used to implement and balance common dietary habits. The general belief is that natural substances reduce the risk of chronic diseases and amplify sports performance with no harmful side effects. Since sports science students will become professionals of sport activities and may also have a role in suggesting the use of dietary supplements to athletes, the aim of this study was to evaluate if physical activity influences the use of drugs and dietary supplements. A modified version of the International Physical Activity Questionnaire—Short Form (IPAQSF) was administered to perform these evaluations. A total of 1452 students from the University of Messina, Italy, enrolled in sports science courses completed the survey; of these, 1075 (704 male and 371 female students) were physically active in moderate- or high-intensity training. Of those physically active students, 709 (440 male and 269 female) were competitive athletes, identified on the basis of their answer to a specific question also indicating the type of sport they practice. The results suggest that 5.6% of all respondents were regular consumers of pharmaceutical products, compared to just 1.0% of the cohort of competing athletes. In contrast, the consumption of natural supplements was similar (14% vs. 15%) between groups. The most frequently used supplements were vitamins, including vitamin C, vitamin B complex, and multivitamin complex, followed by minerals and amino acids or protein complex. The probability of using dietary supplements was mostly related to the male gender (OR 1.64; 95% CI: 1.17–2.30), having a job (OR 1.45; 95% CI: 1.07–1.96), and, most of all, performing physical activity (OR 3.53; 95% CI: 2.18–5.71). The only factor related to a higher use of drugs was female gender (OR 2.40; 95% CI: 1.52–3.79), and the most used class was antihistaminic, followed by FANS. These results suggest that among the specific population of sports science students, those performing physical activity are less prone to using pharmaceutical products and have healthier habits.

The periaqueductal gray is a mesencephalic structure involved in modulation of responses to stressful stimuli. Structural connections between the periaqueductal gray and the cerebellum have been described in animals and in a few diffusion tensor imaging studies. Nevertheless, these periaqueductal gray–cerebellum connectivity patterns have yet to be fully investigated in humans. The objective of this study was to qualitatively and quantitatively characterize such pathways using high-resolution, multi-shell data of 100 healthy subjects from the open-access Human Connectome Project repository combined with constrained spherical deconvolution probabilistic tractography. Our analysis revealed robust connectivity density profiles between the periaqueductal gray and cerebellar nuclei, especially with the fastigial nucleus, followed by the interposed and dentate nuclei. High-connectivity densities have been observed between vermal (Vermis IX, Vermis VIIIa, Vermis VIIIb, Vermis VI, Vermis X) and hemispheric cerebellar regions (Lobule IX). Our in vivo study provides for the first time insights on the organization of periaqueductal gray–cerebellar pathways thus opening new perspectives on cognitive, visceral and motor responses to threatening stimuli in humans.

Background and Objectives: Bones and the skeletal muscle play a key role in human physiology as regulators of metabolism in the whole organism. Bone tissue is identified as a complex and dynamic living unit that could react to physical activity. Hormones, growth factors, signaling factors, and environmental factors control osteogenesis, and it could be regulated at a post-transcriptional level. MicroRNAs (miRNAs) can interfere with mRNAs translation. Increasing data suggest that miRNAs, through different pathways, are involved in the regulation of bone marrow mesenchymal stem cells (BMSCs) differentiation and physical activity-induced bone remodeling. The purpose of this narrative review is to investigate the potential protective role played by physical activity in affecting miRNAs expression in close tissues and elaborate on the complex network of interplay that could drive various metabolic responses of the bone to physical activity. Materials and Methods: A bibliographic search of the scientific literature was carried out in scientific databases to investigate the possible effect of physical activity on age-related features detected in the musculoskeletal system. Results: Several studies suggested that the musculoskeletal system interacting at a biomolecular level could establish crosstalk between bone and muscle in an endocrine or paracrine way through myokines released by muscle at the periosteal interface or in the bloodstream, such as irisin. Mechanical stimuli have a key role in bone formation and resorption, increasing osteogenesis and downregulating adipogenesis of BMSC via regulation of expression of runt-related transcription factor 2 (Runx2) and peroxisome proliferator-activated receptor gamma (PPARγ), respectively. Conclusions: Increasing data suggest that miRNAs, through different pathways, are involved in the regulation of BMSCs differentiation and physical activity-induced bone remodeling. Modulation of miRNAs following physical exercise represents an interesting field of investigation since these non-coding RNAs may be considered defenders against degenerative diseases and as well as useful prognostic markers in skeletal and muscle-skeletal diseases, such as osteoporosis.

Background The coexistence of a double superior vena cava (SVC) and a partially left inferior vena cava (PLIVC) with a circumaortic collar, associated with other congenital malformations, was not described previously. Case Description We present a 33-year-old woman in hemodialysis with complete exhaustion of the brachial routes for vascular access, admitted to our Nephrology Unit for a long-term central venous catheter (CVC) implant, usually by us performed under EchoScopic Technique (EST), an echographic venipuncture followed by continuous radioscopic control of guidewire and catheter in all the steps of implant. An intraoperative venography showed a complete stop of right internal jugular vein, a right SVC, a persistent left SVC, a left inferior vena cava in the iliac and subrenal tracts, a circumaortic venous collar in the renal tract, and normal right suprarenal and hepatic tracts. Conclusions The double SVC was related to the persistence of the caudal part of the anterior cardinal veins. As to the PLIVC, the iliac and subrenal parts of the inferior vena cava can be related to the persistent left supracardinal vein, while the circumaortic venous collar to the persistent intersupracardinal and left subsupracardinal anastomoses. All invasive procedures, and particularly those potentially complicated, must be performed under EST, now considered a mandatory tool for CVC implants, owing to the hypothesis of possible venous congenital anomalies.

Background Diffusion tensor imaging (DTI) is a non-invasive MR technique widely employed to study muscle anatomy. DTI parameters have been used to investigate microstructural changes dependent on demographic factors or transient condition such as exercise. The present study is aimed at investigating the diffusion parameters changes of the human calf muscles after a 3-months strength training protocol. Methods Ten young men were trained for improving size and strength of the medial (GCM), lateral gastrocnemius (GCL) and soleus (SL) three times a week, with at least 24 hours between training sessions, for a period of three months. Diffusion weighted magnetic resonance images were acquired at the beginning of the training period (TPRE) and at three months (TPOST) using a 3T scanner. The fractional anisotropy (FA), mean diffusivity (MD) and tensor eigenvalues (λ1, λ2, λ3) were derived from the diffusion weighted imaging data. Results We found a significant increase in λ1, λ2, λ3 and MD values and muscle volumes between TPRE and TPOST in all the examined muscles both for the left and right side. No significant differences were highlighted for FA. Conclusions DTI enables the investigation of muscle microstructure, allowing for the assessment of diffusion parameters variation of the muscle tissue in response to training thus being a useful tool to investigate physiological and pathological changes in skeletal muscle microstructure which could be employed to test the outcomes and the effectiveness of a given training protocol.

Aims Oxidative stress increase is a key event for development of sensitivity-related illnesses (SRIs). The aim of this work was to evaluate the influence of a genetic variant in the antioxidant enzyme glutathione peroxidase (GPx1) on oxidative stress development in SRIs. Main methods GPx1 rs1800668 genotype, as well as glutathione, ubiquinone, and DNA damage were assessed in 34 SRI patients and 36 healthy subjects. Key findings Total glutathione, reduced/oxidized glutathione, and ubiquinone were significantly decreased in cases compared with controls, while DNA fragmentation was significantly increased in patients. However, these differences were not associated to GPx1 genetic background. Significance GPx1 rs1800668 polymorphism does not play a major role in SRI-related oxidative stress development.

Methylene-tetrahydrofolate reductase (MTHFR) and paraoxonase 1 (PON1) gene polymorphisms have been associated with hyperhomocysteinemia and oxidative stress increase, that are established cardiovascular risk factors. Given that intense physical activity may increase the susceptibility to adverse cardiovascular outcomes, here we investigated the effects of MTHFR C677T and A1298C as well as PON1 Q192R gene polymorphisms on cardiovascular risk markers in twenty-eight male water polo elite players. The mean plasma levels of homocysteine (Hcy) and advanced oxidation protein products (AOPP) were above reference limits in resting conditions, and increased after competition. Moreover, a positive correlation was found between Hcy and AOPP concentrations, and also between their variations (ratio post-exercise/pre-exercise values) and the variations of lactic dehydrogenase (LDH) and creatine kinase (CK) activities, known as muscle damage markers. The highest Hcy and AOPP values were found in subjects having either MTHFR CT/AC or TT/AA, and PON1 QR192 genotype, respectively. After exercise, Hcy concentrations significantly increased in CT/AC or TT/AA subjects than in athletes having other MTHFR genotypes. A training-induced increase in plasma levels of LDH and CK activities, as well as myoglobin concentrations, was also observed, even if significant differences were found only for CK activity in athletes with MTHFR CT/AC or TT/AA athletes.

The sarcoglycan complex is a trans-membrane system playing a key role in mechano-signaling the connection from the cytoskeleton to the extracellular matrix. While β-, δ-, and e-sarcoglycans are widely distributed, γ- and α-sarcoglycans are expressed exclusively in skeletal and cardiac muscle. Insufficient data are available on the distribution of sarcoglycans in nonmuscular tissue. In the present study, we used immunohistochemical and RT-PCR techniques to study the sarcoglycans also in normal human glandular tissue, a type of tissue never studied in relation to the sarcoglycan complex, with the aim of verifying the real wider distribution of this complex. To understand the role of sarcoglycans, we tested specimens collected from patients affected by benign prostatic hyperplasia and adenocarcinoma. For the first time, our results showed that all sarcoglycans are detectable in normal samples both in epithelial and in myoepithelial cells; in pathological prostate, sarcoglycans appeared severely reduced in number or were absent. These data demonstrated that all sarcoglycans have a wider distribution suggesting a new unknown role for these proteins. The decreased number of sarcoglycans, containing cadherin domain homologs in samples of prostate affected by hyperplasia, and the absence of proteins in prostate biopsies, in cases affected by adenocarcinoma, could be responsible for the loss of adhesion between epithelial cells, which in turn facilitates the progression of benign tumors and the invasive potential of malignant tumors. Anat Rec, 297:327–336, 2014. © 2013 Wiley Periodicals, Inc.

Costameres encircle the myocyte perpendicular to its long axis, and comprise two protein complexes: the dystrophin-glycoprotein complex (DGC) and the vinculin-talin-integrin system. They participate in signaling functions and protect muscle cells from damage induced by workload. The behaviour of those proteins has been a focus of study starting from skeletal and smooth muscle cells to cardiomyocytes, and still represents a topical subject for cardiovascular translational research. This review summarizes the past and present novel approaches of our and other groups of work on this subject of research.

Ureteropelvic junction obstruction is one of the most common causes of hydronephrosis in children. A malfunction of smooth muscle cells is believed to be the underlying mechanism causing obstruction. We investigated the expression of some integrins, talin and β-dystroglycan, considered the main compound of smooth muscle cell cytoskeleton, and active caspase 3 at the level of the ureteropelvic junction obstruction.Specimens were obtained at pyeloplasty in 12 children with ureteropelvic junction obstruction. Six control specimens were obtained during organ explantation. Specimens were divided into renal pelvis, ureteropelvic junction and ureter below the obstruction. Western blot analysis of active caspase 3, and immunofluorescence and polymerase chain reaction analysis were performed for α7A, β1A, α7B and β1D integrins, talin and β-dystroglycan.Talin and β-dystroglycan were slightly impaired in ureteropelvic junction obstruction, while α7B and β1D integrins were severely reduced, and α7A, β1A and active caspase 3 were significantly enhanced compared to controls.We demonstrated activation of apoptosis and a critical alteration of cytoskeleton that might explain the altered function and the increased apoptosis in smooth muscle cells in ureteropelvic junction obstruction. The delayed rearrangement of the cytoskeleton of smooth muscle cells in ureteropelvic junction obstruction might be linked to a postnatal splicing from α7A and β1A to α7B and β1D integrins, respectively. This relationship could explain the common clinical scenario of spontaneous improvement of hydronephrosis in children with suspected ureteropelvic junction obstruction.

Objectives To investigate the distribution of MTHFR C677T and A1298C as well as PON1 Q192R gene polymorphisms, known to be involved in hyperhomocysteinemia-related cardiovascular risk, in elite athletes. Design and methods Genetic background at MTHFR and PON1 loci and plasma levels of homocysteine, folate, vitamin B 12 and advanced oxidation protein product (AOPP) levels were assessed in thirty-seven 400 m male hurdlers and thirty-four sedentary subjects. Results Homocysteine plasma levels and AOPPs were significantly higher in hurdlers bearing the TT677/AA1298 diplotype than in both hurdlers and sedentary subjects with other diplotypes. A positive dependence between either homocysteine or AOPP plasma levels and MTHFR , but not PON1 genotype, was observed in hurdlers. Conclusions Elite hurdlers, having an unfavorable MTHFR genotype are exposed to increased cardiovascular risk, dependent on alterations of homocysteine and AOPP plasma levels.

The muscle nicotinic acetylcholine receptor (AChR) turns over at different rates depending on stage of synaptogenesis and innervation. Tyrosine phosphorylation modulates desensitization, interaction with cytoskeleton and lateral mobility in the membrane of AChR. To determine whether tyrosine phosphorylation also modulates the turnover of AChR, myotubes in vitro were exposed to the tyrosine phosphatase inhibitor pervanadate. Our data indicate that a transient increase of phosphotyrosine levels stabilized a fraction of AChRs. The effects were limited to the non-epsilon subunit-containing AChRs already present in the membrane. Tyrosine phosphorylation of the receptor occurred on the beta subunit, was transient and stable molecules were not selectively tyrosine phosphorylated. The data indicate that modulation of phosphotyrosine levels in muscle cells provides signals to control AChR metabolic stability.

Background The costameres in skeletal muscle fibers were first described by Pardo et al. (1983a) and have been defined as transverse circumferential elements of the cytoskeleton associated to the sarcolemma. Specific immunostaining for vinculin shows that the costameres overlie I bands. However, an exact correlation between the costameres and the Z line is uncertain, although ∼10 proteins so far have been localized in the costameres. To define the exact localization of costameres in human skeletal muscle fibers, we carried out an immunofluorescence study using confocal scanning laser microscopy on the fascia lata muscle of adult males. Methods Samples were fixed in 3% paraformaldehyde; frozen sections were treated with antivinculin, antitalin, antidesmin, and anti-α-actinin, then immunostained with TRITC. For double localization, the TRITC-streptavidin, as a marker for vinculin and FITC-streptavidin a marker for desmin, were used. Results The distance between two subsequent transverse lines of actin-inf indicated that muscle fibers were well stretched. Processing, with different software functions of the images obtained using CLSM, shows that vinculin and talin are only present in the sarcolemmal lattice. Immunostaining for vinculin and double immunostaining for vinculin and desmin demonstrate that costameres superimpose underlying I bands without interruption at the Z line. Immunostaining for talin showed that the protein is located in correspondence with the I band and M line. Conclusions We believe that costameres are “proteic machinery.” The findings of the present study suggest that it is possible to determine the width and the period of each proteic component. In addition, we indicate that costameres are present in correspondence with M line. © 1996 Wiley-Liss, Inc.

Morphological and volumetric variabilities of lateral ventricles are considered indirect indicators of age-and gender-related reductions of white and gray matter. However, no studies have classified lateral ventricles with different morphologies or showed its asymmetric shapes in healthy subjects. We performed an analysis on living subjects, using 3D volume rendering techniques. Eighty-five healthy Caucasian volunteers (49 women and 36 men aged 19–69 years) were scanned by a Philips Achieva 3T R2.6. Three-dimensional reconstruction allowed us to identify three main morphological shapes in living subjects and to show asymmetries between horns. We also assessed the surface deformation of the cerebral ventricles to identify region-specific shape differences in aging healthy adults. Statistical analysis showed significant gender- and age-related volume differences. An increase in lateral ventricle volume appears to be a constant, linear function of age throughout adult life.

During neuromuscular junction maturation, the rapidly degrading receptors (Rr; t1/2 approximately equal to 1 day) are replaced by metabolically stable molecules (Rs; t1/2 approximately equal to 10 days). Rr and Rs do not interconvert, are differently regulated after denervation in adult muscle and are endowed of unique responses to stabilizing agents. In cultured rat myotubes all the epsilon subunit-containing acetylcholine receptors (epsilon-AchRs) are of the Rs type. In the present study we show that Rs exist also in absence of epsilon-AChR and that nonepsilon-(presumably gamma-)AChRs can be included in the Rs pool when epsilon-AChR expression is low. The data indicate that Rs metabolic properties are independent of AChR subunit composition and that epsilon subunit is a signal to efficiently sort AChR molecules to the Rs pool.

Costameres were identified, for the first time, in skeletal and cardiac muscle, as regions associated with the sarcolemma, consisting of densely clustered patches of vinculin; they have many characteristics common to the cell-extracellular matrix-type of adherens junctions. Costameres are considered 'proteic machinery' and they appear to comprise two protein complexes, the dystrophin-glycoprotein complex (DGC) and the vinculin-talin-integrin system. In comparison to skeletal muscle, few studies have focused on cardiac muscle regarding these two complexes, and study is generally relative to dystrophin or to cardiac diseases, such as cardiomyopathies. However, insufficient data are available on these proteins in healthy human cardiomyocytes. For this reason, we performed an immunohistochemical study using human cardiac muscle fibers, in order to define the real distribution and the spatial relationship between the proteins in these two complexes. Our data showed a real costameric distribution of DGC and of the vinculin-talin-integrin system; all tested proteins were present in T-tubule and in intercalated disks. Moreover, our data demonstrated that all tested proteins of DGC colocalized with each other, as all tested components of the vinculin-talin-integrin system, and that all tested proteins of DGC colocalized with all tested proteins of the vinculin-talin-integrin system. Finally, all tested proteins of the two complexes were localized in the region of the sarcolemma over the I band, in 100% of our observations. The present study, for the first time, analyzed the majority of proteins of DGC and of the vinculin-talin-integrin system in cardiac muscle fibers, and it confirmed that DGC and the vinculin-talin-integrin system have a role in the transduction of mechanical force to the extracellular matrix. Finally it attributed a key role in the regulation of action potential duration to cardiac myocytes.