Ultrasonographic soft markers for detection of rectosigmoid deep endometriosis.

OBJECTIVES: The aim of this study was to evaluate the use of ultrasound (US) soft markers as a first-line imaging tool to raise suspicion of rectosigmoid (RS) involvement in women suspected of having deep endometriosis. METHODS: We included in this prospective observational study all patients with clinical suspicion of deep endometriosis who underwent diagnostic transvaginal US evaluation at our unit from January 2016 to February 2017. Several US soft markers were evaluated for prediction of RS involvement (presence of US signs of uterine adenomyosis, presence of an endometrioma, adhesion of the ovary to the uterus (reduced ovarian mobility), presence of 'kissing ovaries' (KO) and absence of the 'sliding sign'), using as the gold standard expert US examination for the presence of RS endometriosis. RESULTS: Included were 333 patients with clinical suspicion of deep endometriosis. Of these, 106 had an US diagnosis of RS endometriosis by an expert. The only significant variables found in the prediction model were absence of the sliding sign (odds ratio (OR), 13.95; 95% CI, 7.7-25.3), presence of KO (OR, 22.5; 95% CI, 4.1-124.0) and the interaction between these two variables (OR, 0.03; 95% CI, 0.004-0.28). Regarding their interaction, RS endometriosis was present when KO was absent and the sliding sign was present in 10% (19/190) of cases, when both KO and the sliding sign were present in 71.4% (5/7) of cases, when both KO and the sliding sign were absent in 60.8% (76/125) of cases and when KO was present and the sliding sign was absent in 54.5% (6/11) of cases. Thus, when the sliding sign was absent and/or KO was present, transvaginal US showed a specificity of 75% (95% CI, 69-80%) and a sensitivity of 82% (95% CI, 73-88%). CONCLUSIONS: US findings of absence of the sliding sign and/or presence of KO in patients with clinical suspicion of endometriosis should raise suspicion of RS involvement and indicate referral for expert US examination, with a low rate of false-negative diagnosis. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Targeting Alzheimer's disease with gene and cell therapies.

Alzheimer's disease (AD) causes dementia in both young and old people affecting more than 40 million people worldwide. The two neuropathological hallmarks of the disease, amyloid beta (Aß) plaques and neurofibrillary tangles consisting of protein tau are considered the major contributors to the disease. However, a more complete picture reveals significant neurodegeneration and decreased cell survival, neuroinflammation, changes in protein and energy homeostasis and alterations in lipid and cholesterol metabolism. In addition, gene and cell therapies for severe neurodegenerative disorders have recently improved technically in terms of safety and efficiency and have translated to the clinic showing encouraging results. Here, we review broadly current data within the field for potential targets that could modify AD through gene and cell therapy strategies. We envision that not only Aß will be targeted in a disease-modifying treatment strategy but rather that a combination of treatments, possibly at different intervention times may prove beneficial in curing this devastating disease. These include decreased tau pathology, neuronal growth factors to support neurons and modulation of neuroinflammation for an appropriate immune response. Furthermore, cell based therapies may represent potential strategies in the future.

Identification of a HERV-K env surface peptide highly recognized in Rheumatoid Arthritis (RA) patients: a cross-sectional case-control study.

Endogenous retroviruses (HERV) are believed to be pathogenic in several autoimmune diseases. Among them, HERV-K viruses have been reported recently to be involved in the pathogenesis of rheumatoid arthritis (RA). In this study we have explored the role of humoral immune response against HERV-K as a potential pathogenetic mechanism in RA. Four different peptides from the extracellular portion of the env protein of HERV-K (env-su19-37 , env-su109-126 , env-su164-186 , env-su209-226 ) were selected by bioinformatic analysis on the basis of their putative immunogenicity. Indirect enzyme-linked immunosorbent assay (ELISA) was then carried out to quantify antibodies against those peptides on blood samples of 70 consecutive RA patients and 71 healthy controls (HC). Differences between the two groups were analysed using the Mann-Whitney test. Potential correlations between RA laboratory, clinical descriptors and immunoglobulin (Ig)G levels were explored by bivariate regression analysis. Serum autoantibodies against one of four tested peptides of HERV-K (env-su19-37 ) were significantly higher in RA than in HC (19 versus 3%, P = 0·0025). Subgroup analysis showed no association between anti-HERV-K peptide humoral response and clinical, serological and clinimetric RA disease descriptors. Serum from RA patients in our series reacted significantly against HERV-K env-su19-37 peptide in comparison to the general population suggesting a role for the HERV-K- related, secondary antigenic-driven immune response in the pathogenesis of RA. Further studies are needed to confirm these results and to explore the role of this HERV-K surface peptide as a potential therapeutic target.

Low-level laser therapy and invisible removal aligners.

It seems that Low Level Laser Therapy (LLLT) stimulates orthodontic tooth movements, increasing the alveolar bone turnover. The aim of this study is to evaluate how LLLT can influence the orthodontic treatment with invisible removal aligner. A sample of 21 subjects was divided into two groups, a laser group (10 patients) and a control group (11 patients). All subjects were instructed to wear each aligner 12 hours a day for 2 weeks. Laser external bio-stimulation was given in the laser group every second week. The laser group successfully finished the treatment, while at 3rd – 5th aligner the control group did not finish the treatment. Laser treatment seemed to be better than treatment without laser. LLLT combined with aligners is able to favour, in 12 hours, the same tooth movement obtained by wearing the aligner 22 hours a day, according to the traditional protocol. This aspect could be useful for those patients who prefer not to use the aligners during the day. LLLT makes invisible removal aligner treatment more comfortable also because during the day the patients have to wear the aligners less hours than the treatment without laser.

Evaluation of fatty acid composition and antimicrobial activity of supercritical fluid extract of Rubus ulmifolius Schott fruits.

In this study, we continue our research on Rubus ulmifolius Schott extracts obtained by supercritical fluid extraction (SFE) using CO2 as solvent. Extraction experiments were carried out at pressures of 300 bar and a temperature of 40 °C, SFE [300:40], on mature fruits of R. ulmifolius. The fatty acid (FA) profile of extracts was assessed by reversed-phase HPLC-DAD/ELSD analysis. The most represented fatty acids in the extract were linoleic acid (386 mg/g), oleic acid (210 mg/g), linolenic acid (112 mg/g), palmitic acid (48 mg/g), and stearic acid (40 mg/g). SFE extraction showed a total FA amount of 795.8 mg/g of dry weight. The chemical and biological characteristics of this extract were compared with those obtained with different extraction methods. Following the diffusion-susceptibility test, three fruit extracts, SFE [300:40], Sx, and MEtOH, didn't show an inhibition profile against Streptococcus mutans. Kirby-Bauer analysis showed only the methanolic extract demonstrated antimicrobial activity with 11-mm inhibition diameter.

IOTA simple rules for discriminating between benign and malignant adnexal masses: prospective external validation.

OBJECTIVE: To determine the diagnostic performance of International Ovarian Tumor Analysis (IOTA) 'simple' rules for discriminating between benign and malignant adnexal masses. METHODS: A prospective study was performed between January 2011 and June 2012. Eligible patients were women diagnosed with a persistent adnexal mass who presented to the participating centers. Four trainees evaluated the adnexal mass by transvaginal ultrasound under the supervision of an expert examiner. The trainee analyzed the mass according to IOTA simple rules and provided a diagnosis of benign, malignant or inconclusive. All women included in the study underwent surgery and tumor removal in the center of recruitment. Diagnostic performance was assessed by calculating sensitivity, specificity and positive (LR+) and negative (LR-) likelihood ratios. RESULTS: A total of 340 women were included (mean patient age, 42.1 (range, 13-79) years). Of the tumors, 55 (16.2%) were malignant and 285 (83.8%) were benign. The IOTA simple rules could be applied in 270 (79.4%) cases. In these cases, sensitivity was 87.9% (95% CI, 72.4-95.2), specificity 97.5% (95% CI, 94.6-98.8), LR+ 34.7 (95% CI, 15.6-77.3) and LR- 0.12 (95% CI, 0.05-0.31). CONCLUSIONS: Application of the IOTA simple rules yielded acceptable results in terms of specificity in the hands of non-expert examiners. However, with non-expert examiners there was a 12% false-negative rate, which is relatively high.

Supercritical extraction of volatile and fixed oils from Petroselinum crispum L. seeds: chemical composition and biological activity.

The supercritical fluid extraction (SFE) of volatile and fixed oil from milled parsley (Petroselinum crispum L.) seeds, using CO2 as solvent, is presented in this study. Extraction experiments were carried out in two steps: at pressures of (90 or 300) bar and temperature of 40 °C. The first extraction step, performed at 90 bar, produced a volatile fraction mainly formed by apiole (82.1%) and myristicin (11.4%). The volatile oil yield was 2.6% by weight of the charge. The second extraction step, carried out at 300 bar produced a fixed oil at a yield of 0.4% by weight. The most represented fatty acids in P. crispum fixed oil were 18:1 n-12 (49.9%), 18:2 n-6 (18.2%), 18:1 n-9 (11.8%), and 16:0 (7.4%). In particular, the unsaturated fatty acids 18:1 n-12 and 18:1 n-9 averaged 182.2 mg/g and 92.1 mg/g of oil extract, respectively. The quality of the oils extracted by SFE, in terms of its chemical composition, was compared to the oils obtained by hydrodistillation (HD) in a Clevenger apparatus and by solvent extraction (SE) using n-hexane in a Soxhlet apparatus. The antioxidant properties were determined by means of the ABTS assay. The results indicated that the fixed oil possessed low antioxidant activity (EC50 = 0.4 mg/mL) and the volatile oil had no antioxidant activity. The total phenolic content, expressed as concentration of gallic acid (gallic acid equivalent, GAE), of the fixed oil was 1.5 mg/g. The fixed oil found to have inhibitory effects against α-glucosidase, the volatile oil is active on acetylcholinesterase (AChE), tyrosinase, and α-glucosidase. Both samples have weak inhibitory activity on α-amylase and no activity on butyrylcholinesterase (BChE).

Epidemiology of dental professional liability.

The aim of this article is to collect data relating to dental professional liability in Italy and provide a common platform for discussions among clinicians, legal medicine practitioners, and experts in law. On the basis of two different dental-legal statistical samples (1,670 reports of legal dental experts and 320 civil court decisions) we analyzed the dental professional liability lawsuit in the areas of distribution of lawsuits among the different dental specialties, recurrence and type of errors, outcome of civil suits, parameters of compensation. Some ideas are also proposed for possible strategies in the management of clinical risk (prevention of errors) and court proceedings.

Antifungal activity of essential oil from Mentha spicata L. and Mentha pulegium L. growing wild in Sardinia island (Italy).

This study aims to evaluate the antifungal activity of Mentha spicata L. and Mentha pulegium L. from Sardinia and to assess their efficacy on virulence factors for Candida albicans, particularly on the inhibition of the germ tube formation. The major compounds of the essential oils were carvone (62.9%) for M. spicata and pulegone (86.2%) for M. pulegium. The essential oil from M. spicata showed a more preeminent effect against Cryptococcus neoformans and the dermatophytes Trichophyton rubrum and T. verrucosum (0.32 µL/mL). Both oils were very effective in inhibiting C. albicans germ tube formation, at doses well below their MIC (0.16 µL/mL).

Radiofrequency thermoablation (RFA) and radiotherapy (RT) combined treatment for bone metastases: a systematic review.

OBJECTIVE: Approximately 50% of cancer patients develop bone metastases in their natural disease history. The management of metastatic bone disease requires a multidisciplinary approach. Both radiofrequency ablation (RFA) and radiation therapy (RT) were safe and effective in the management of painful metastases, even if they rely on totally different action mechanisms. A synergistic combination of RT and RFA seems to result in a better pain control. A systematic review was performed to describe the feasibility and effectiveness of the association between RFA and RT in the treatment of metastatic bone pain in oligo-metastatic patients, evaluating its role in alleviating bone pain, reducing the risk of fractures, and consequently ensuring a better quality of life. MATERIALS AND METHODS: A systematic database search was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This systematic review included studies that reported populations meeting the following inclusion criteria: (I) confirmed bone metastases in adult patients; (II) active bone metastases pain; (III) patients treated with combined RFA-RT; (IV) Original studies. RESULTS: Three papers that evaluated the combined treatment with doses ranging from moderately hypofractionated three-dimensional conformal RT (3D-CRT) and stereotactic body radiation therapy (SBRT) schedules were selected. CONCLUSIONS: The RFA-RT combined strategy appears to be promising in terms of efficiency and safety with adequate pain control and quality of life improvement. Positive effects on time to local failure and overall survival increase were also observed. Further prospective studies are needed to better delineate RFA-RT treatment benefits.

Mammary Paget's disease and radiotherapy: a systematic literature review.

OBJECTIVE: Paget disease of the breast (PDB) is a rare form of cutaneous breast cancer. Up to date, no randomized studies evaluated the different management strategies. This systematic review investigates the role of radiotherapy and its best technical profile in the treatment of this disease, with great attention to doses and fractionation regimens. MATERIALS AND METHODS: A systematic search was performed on PubMed, Embase and Scopus in order to detect case reports, case series and prospective as well as retrospective clinical studies describing histologically proven PDB and providing information about pertinent radiation treatments. Searching strategy followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. RESULTS: Inclusion criteria were met by six papers, dealing with radiation treatments performed postoperatively and in exclusive settings. No evaluations were performed on preoperative radiotherapy. CONCLUSIONS: Actually, the standard treatment of PDB reflects oncological principles of breast carcinoma therapy, including the role of breast-preserving surgery. The traditional radiotherapic dose is 50 Gy, with daily fractionation of 2 Gy. Adjuvant radiotherapy following breast preserving surgery represents the current standard of care; prospective studies could be of help in defining the role of exclusive radiotherapy, hypofractionated schemes and smaller target volumes.

A study of saccadic eye movement dynamics in volleyball: comparison between athletes and non-athletes.

AIM: Visual search strategy in sports may influence performance. Thus it is interesting to investigate oculo-motor behavior of athletes and its possible impingement upon sport training and coaching. The differences in fixations and saccadic eye movements between expert volleyball players and novice subjects was studied, by carrying out a precise analysis of gaze shifts during the observation of a standard game situation. METHODS: Fifteen professional athletes and fifteen non athletes watched at a volleyball filmed sequence in which a setter receives a pass tossed from the coach and sets it forward or backward. Then, the number and duration of fixations to specific interest areas (IAs) were counted. In addition, the sequences of saccades from each IA to the others were analyzed. RESULTS: The results showed that expert players performed fewer fixations of longer duration and spent more time looking first at the initial pass trajectory and then at the setter's hands, disregarding the ball trajectory. The non athletes, instead, followed the whole course of the ball, before and after the hands touch. CONCLUSION: These findings support the interpretation that experts volleyball players extract more task-relevant information from each fixation than do less skilled athletes, and that player's proficiency influences the strategy used in the treatment of visual information.

Spatially fractionated radiotherapy (SFRT) targeting the hypoxic tumor segment for the intentional induction of non-targeted effects: An in silico study to exploit a new treatment paradigm.

INTRODUCTION: The possibility of intentionally triggering non targeted effects (NTEs) using spatially fractionated radiotherapy (SFRT) alone or combined with immunotherapy is an intriguing and fascinating area of research. Among different techniques for SFRT, stereotactic body radiotherapy targeting exclusively the central hypoxic segment of bulky tumors, (SBRT-PATHY) might trigger immunogenic cell death more efficiently. This in silico study aims to identify the best possible dosimetric trade-off for prescribing SFRT with volumetric modulated arc (VMAT) based stereotactic radiotherapy (SRT). MATERIAL AND METHODS: Eight spherical volumes defined "Gross Tumor Volumes" (GTVs) were generated with diameters of 3-10 cm (with incremental steps of 1 cm), simulating tumor lesions. The inner third part of each GTV (GTVcentral) was selected to simulate the central hypoxic area and a ring structure was derived around it to simulate the tumor periphery (GTVperipheral). Volumetric modulated arc radiation treatment (VMAT) plans were calculated to deliver a single fraction of 10 Gy to each GTVcentral with different dose prescription methods: target mean and isodose driven (40, 50, 60, 70, 80 and 90%).The volume of GTVperipheral receiving less than 2 Gy was recorded as dosimetric performance indicator. RESULTS: 56 possible dosimetric scenarios were analyzed. The largest percentage of GTVperipheral spared from the dose of 2 Gy was achieved with dose prescription methods to the 70% isodose line for lesions smaller than 6 cm (range 42.9-48.4%) and to the target mean for larger ones (range 52.9-64.5%). CONCLUSIONS: Optimizing the dose prescription method may reduce the dose to tumor periphery in VMAT-based SFRT, thus potentially sparing tumor infiltrating immune cells. The optimal method may vary according to the size of the lesion. This should be taken into account when designing prospective trials using SFRT.

Modifications of periodontal tissues associated with Williams syndrome. A case report.

Williams syndrome, also known as Williams-Beuren syndrome, or elfin-facies syndrome, was described by Dr. Williams and Dr. Beuren for the first time in 1961 and 1962. This multisystem, congenital and panethnic disorder is characterized by a number of developmental and physical abnormalities like excess of gingiva. The goal of this article is to present the application of a protocol of periodontal treatment leading to the functional rehabilitation of the oral areas affected by excess of gingiva. A 19-year-old boy, diagnosed as suffering from Williams Syndrome, was brought to the dental school, University of Cagliari, seeking for orthodontic and periodontal treatment. During the consultation the excess of gingiva needing periodontal treatment was noticed. This report reveals a classic presentation of the syndrome, with emphasis on its oral and periodontal manifestations. Periodontal management included periodontal flap surgery to treat the excess of gingiva performing clinical crown lengthening. Re-evaluation of the patient after two months showed remarkable reduction of the excess of gingiva. Williams syndrome is clinically important to the periodontist, because of its associated features of excess of gingiva. Periodic examinations are recommended to identify any possible recurrence or complications.

6-Hydroxydopamine lesion in the ventral tegmental area fails to reduce extracellular dopamine in the cerebral cortex.

Dopamine and noradrenaline are both involved in modulation of superior cognitive functions that are mainly dependent on frontal cortex activity. Experimental evidence points to parallel variations in extracellular concentrations of catecholamines in the cerebral cortex, which leads us to hypothesize their corelease from noradrenergic neurons. This study aimed to verify this hypothesis, by means of cerebral microdialysis following destruction of dopaminergic innervation in rats. The unilateral injury of dopaminergic neurons, by 6-hydroxydopamine injection in the ventral tegmental area, dramatically reduced the immunoreactivity for dopamine transporter in the cerebral hemisphere ipsilateral to the lesion. Tissue dopamine content in the ipsilateral nucleus accumbens and medial prefrontal and parietal cortex was also profoundly decreased, whereas noradrenaline was only slightly affected. Despite the lower tissue content in the denervated side, the extracellular dopamine level was not changed in the cortex, although it was markedly decreased in the nucleus accumbens ipsilateral to the lesion. The effect of drugs selective for D(2)-dopaminergic (haloperidol) or alpha(2)-noradrenergic (RS 79948) receptors was verified. Haloperidol failed to modify extracellular dopamine in either cortex but increased it in the nucleus accumbens, such an increase being greatly reduced in the denervated side. On the other hand, RS 79948 increased extracellular dopamine and DOPAC in all areas tested, the increases being of the same degree in both intact and lesioned sides. The results strongly support the hypothesis that the majority of extracellular dopamine in the cortex, unlike that in the nucleus accumbens, originates from noradrenergic terminals.

Cannabinoid CB1 receptors in the paraventricular nucleus and central control of penile erection: immunocytochemistry, autoradiography and behavioral studies.

[N-(piperidin-1-yl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazole-3-carboxyamide] (SR 141716A), a selective cannabinoid CB1 receptor antagonist, injected into the paraventricular nucleus of the hypothalamus (PVN) of male rats, induces penile erection. This effect is mediated by the release of glutamic acid, which in turn activates central oxytocinergic neurons mediating penile erection. Double immunofluorescence studies with selective antibodies against CB1 receptors, glutamic acid transporters (vesicular glutamate transporters 1 and 2 (VGlut1 and VGlut2), glutamic acid decarboxylase-67 (GAD67) and oxytocin itself, have shown that CB1 receptors in the PVN are located mainly in GABAergic terminals and fibers surrounding oxytocinergic cell bodies. As GABAergic synapses in the PVN impinge directly on oxytocinergic neurons or on excitatory glutamatergic synapses, which also impinge on oxytocinergic neurons, these results suggest that the blockade of CB1 receptors decreases GABA release in the PVN, increasing in turn glutamatergic neurotransmission to activate oxytocinergic neurons mediating penile erection. Autoradiography studies with [(3)H](-)-CP 55,940 show that chronic treatment with SR 141716A for 15 days twice daily (1 mg/kg i.p.) significantly increases the density of CB1 receptors in the PVN. This increase occurs concomitantly with an almost twofold increase in the pro-erectile effect of SR 141716A injected into the PVN as compared with control rats. The present findings confirm that PVN CB1 receptors, localized mainly in GABAergic synapses that control in an inhibitory fashion excitatory synapses, exert an inhibitory control on penile erection, demonstrating for the first time that chronic blockade of CB1 receptors by SR 141716A increases the density of these receptors in the PVN. This increase is related to an enhanced pro-erectile effect of SR 141716A, which is still present 3 days after the end of the chronic treatment.

Activation of GABA(B) receptors reverses spontaneous gating deficits in juvenile DBA/2J mice.

RATIONALE: Gamma-amino-butyric acid (GABA)(B) receptors play a key role in the pathophysiology of psychotic disorders. We previously reported that baclofen, the prototypical GABA(B) agonist, elicits antipsychotic-like effects in the rat paradigm of prepulse inhibition (PPI) of the startle, a highly validated animal model of schizophrenia. OBJECTIVES: We studied the role of GABA(B) receptors in the spontaneous PPI deficits displayed by DBA/2J mice. MATERIALS AND METHODS: We tested the effects of baclofen (1.25-5 mg/kg, intraperitoneal [i.p.]) in DBA/2J and C57BL/6J mice, in comparison to the antipsychotic drugs haloperidol (1 mg/kg, i.p.) and clozapine (5 mg/kg, i.p.). Furthermore, we investigated the expression of GABA(B) receptors in the brain of DBA/2J and C57BL/6J mice by quantitative autoradiography. RESULTS: Baclofen dose-dependently restored PPI deficit in DBA/2J mice, in a fashion similar to the antipsychotic clozapine (5 mg/kg, i.p.). This effect was reversed by pretreatment with the GABA(B) antagonist SCH50211 (50 mg/kg, i.p.). In contrast, baclofen did not affect PPI in C57BL/6J mice. Finally, quantitative autoradiographic analyses assessed a lower GABA(B) receptor expression in DBA/2J mice in comparison to C57BL/6J controls in the prefrontal cortex and hippocampus but not in other brain regions. CONCLUSIONS: Our data highlight GABA(B) receptors as an important substrate for sensorimotor gating control in DBA/2J mice and encourage further investigations on the role of GABA(B) receptors in sensorimotor gating, as well as in the pathophysiology of psychotic disturbances.

Dysregulation of the endogenous cannabinoid system in adult rats prenatally treated with the cannabinoid agonist WIN 55,212-2.

Cannabis is widely abused by women at reproductive age and during pregnancy. Animal studies showed a particular vulnerability of the developing brain to prenatal chronic cannabinoid administration. We determined whether prenatal exposure to WIN 55,212-2, a potent cannabinoid receptor agonist, affected (1) density, affinity and/or function of cannabinoid CB(1) receptors, (2) endogenous levels of the endocannabinoid anandamide, (3) activities of the major anandamide synthesising and hydrolysing enzymes, N-acyl-phosphatidylethanolamine-specific phospholipase D (NAPE-PLD) and fatty acid amide hydrolase (FAAH), respectively, in brain areas of adult male offspring rats. Furthermore, the effect of prenatal WIN 55,212-2 on spontaneous motility was analyzed. Pregnant rats were treated daily with WIN 55,212-2 (0.5 mg/kg, gestation day 5-20) or vehicle. [(3)H]CP 55,940 and WIN 55,212-2-stimulated [(35)S] GTPgammaS binding were carried out in cerebellum, cerebral cortex, hippocampus, striatum and limbic areas of male adult offspring. Levels of anandamide, FAAH and NAPE-PLD activity were also determined. EC(50) values for WIN 55,212-2-stimulated [(35)S]GTPgammaS binding were significantly different in hippocampus (-26%) and striatum (+27%) in WIN 55,212-2-treated rats. Cannabinoid CB(1) receptor density and affinity were not affected in any analyzed region. In the striatum, increased anandamide levels were associated with reduced FAAH and enhanced NAPE-PLD activities. Opposite changes in anandamide levels and enzymatic activities were detected in limbic areas of WIN 55,212-2-treated rats. Ambulatory activity between WIN 55,212-2- and vehicle-treated adult offspring did not vary. Our results show that prenatal exposure to cannabinoid agonist induces a long-term alteration of endocannabinoid system in brain areas involved in learning-memory, motor activity and emotional behavior.

Biodegradable nanomats produced by electrospinning: expanding multifunctionality and potential for tissue engineering.

With increasing interest in nanotechnology, development of nanofibers (n-fibers) by using the technique of electrospinning is gaining new momentum. Among important potential applications of n-fiber-based structures, scaffolds for tissue-engineering represent an advancing front. Nanoscaffolds (n-scaffolds) are closer to natural extracellular matrix (ECM) and its nanoscale fibrous structure. Although the technique of electrospinning is relatively old, various improvements have been made in the last decades to explore the spinning of submicron fibers from biodegradable polymers and to develop also multifunctional drug-releasing and bioactive scaffolds. Various factors can affect the properties of resulting nanostructures that can be classified into three main categories, namely: (1) Substrate related, (2) Apparatus related, and (3) Environment related factors. Developed n-scaffolds were tested for their cytocompatibility using different cell models and were seeded with cells for to develop tissue engineering constructs. Most importantly, studies have looked at the potential of using n-scaffolds for the development of blood vessels. There is a large area ahead for further applications and development of the field. For instance, multifunctional scaffolds that can be used as controlled delivery system do have a potential and have yet to be investigated for engineering of various tissues. So far, in vivo data on n-scaffolds are scarce, but in future reports are expected to emerge. With the convergence of the fields of nanotechnology, drug release and tissue engineering, new solutions could be found for the current limitations of tissue engineering scaffolds, which may enhance their functionality upon in vivo implantation. In this paper electrospinning process, factors affecting it, used polymers, developed n-scaffolds and their characterization are reviewed with focus on application in tissue engineering.