Effects of the glial modulator palmitoylethanolamide on chronic pain intensity and brain function.

Background: Chronic neuropathic pain (NP) is a complex disease that results from damage or presumed damage to the somatosensory nervous system. Current treatment regimens are often ineffective. The major impediment in developing effective treatments is our limited understanding of the underlying mechanisms. Preclinical evidence suggests that glial changes are crucial for the development of NP and a recent study reported oscillatory activity differences within the ascending pain pathway at frequencies similar to that of cyclic gliotransmission in NP. Furthermore, there is evidence that glial modifying medications may be effective in treating NP. The aim of this Phase I open-label clinical trial is to determine whether glial modifying medication palmitoylethanolamide (PEA) will reduce NP and whether this is associated with reductions in oscillatory activity within the pain pathway. Methods: We investigated whether 6 weeks of PEA treatment would reduce pain and infra-slow oscillatory activity within the ascending trigeminal pathway in 22 individuals (17 females) with chronic orofacial NP. Results: PEA reduced pain in 16 (73%) of the 22 subjects, 11 subjects showed pain reduction of over 20%. Whilst both the responders and non-responders showed reductions in infra-slow oscillatory activity where orofacial nociceptor afferents terminate in the brainstem, only responders displayed reductions in the thalamus. Furthermore, functional connections between the brainstem and thalamus were altered only in responders. Conclusion: PEA is effective at relieving NP. This reduction is coupled to a reduction in resting oscillations along the ascending pain pathway that are likely driven by rhythmic astrocytic gliotransmission

Avulsion fracture of the anterior superior iliac spine: misdiagnosis of a bone tumour

Avulsion fractures of the anterior superior iliac spine are rare. This injury is usually seen in adolescents, as an avulsion fracture of the apophyses, a result of sudden vigorous contraction or repetitive contraction of the sartorius and tensor fasciae latae muscles. Treatment for this injury is usually conservative; however, surgical management has been reported in those with significant displacement. We present a 14 year old male patient who was referred to our unit for biopsy of a possible pathological fracture of his right ilium. The authors feel it is essential to understand the importance of ruling out a bone tumour, if the possibility has been raised, before managing a suspected fracture. If there is any doubt, the case should be referred to an appropriate sarcoma unit for review prior to any intervention

Positron and positronium annihilation patterns in zeolites and bulk ceramics

Positron lifetime (LT) measurements have revealed that in porous media the annihilation pattern is probably dominated by a near-saturation level trapping both for the positron and the positronium as well, which masks the contribution from the ldquofree annihilationrdquo, i.e., annihilation from delocalised positrons. In this work we compare positron lifetime spectra of crystalline zeolites with bulk ceramic materials fabricated by sintering from the same constituents as the zeolites and analyse common features and differences between them. For the dense ceramic samples the contribution from long-living components to the annihilation pattern is substantially lower than that for the zeolites. The results are analysed with the aim to extract new knowledge for the zeolites and for the sensitivity limits for free volume studies in ceramics. (© 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Special considerations for studies of extracellular vesicles from parasitic helminths: a community-led roadmap to increase rigour and reproducibility

Over the last decade, research interest in defining how extracellular vesicles (EVs) shape cross-species communication has grown rapidly. Parasitic helminths, worm species found in the phyla Nematoda and Platyhelminthes, are well-recognised manipulators of host immune function and physiology. Emerging evidence supports a role for helminth-derived EVs in these processes and highlights EVs as an important participant in cross-phylum communication. While the mammalian EV field is guided by a community-agreed framework for studying EVs derived from model organisms or cell systems [e.g., Minimal Information for Studies of Extracellular Vesicles (MISEV)], the helminth community requires a supplementary set of principles due to the additional challenges that accompany working with such divergent organisms. These challenges include, but are not limited to, generating sufficient quantities of EVs for descriptive or functional studies, defining pan-helminth EV markers, genetically modifying these organisms, and identifying rigorous methodologies for in vitro and in vivo studies. Here, we outline best practices for those investigating the biology of helminth-derived EVs to complement the MISEV guidelines. We summarise community-agreed standards for studying EVs derived from this broad set of non-model organisms, raise awareness of issues associated with helminth EVs and provide future perspectives for how progress in the field will be achieved

Special considerations for studies of extracellular vesicles from parasitic helminths: A community‐led roadmap to increase rigour and reproducibility

Over the last decade, research interest in defining how extracellular vesicles (EVs) shape cross-species communication has grown rapidly. Parasitic helminths, worm species found in the phyla Nematoda and Platyhelminthes, are well-recognised manipulators of host immune function and physiology. Emerging evidence supports a role for helminth-derived EVs in these processes and highlights EVs as an important participant in cross-phylum communication. While the mammalian EV field is guided by a community-agreed framework for studying EVs derived from model organisms or cell systems [e.g., Minimal Information for Studies of Extracellular Vesicles (MISEV)], the helminth community requires a supplementary set of principles due to the additional challenges that accompany working with such divergent organisms. These challenges include, but are not limited to, generating sufficient quantities of EVs for descriptive or functional studies, defining pan-helminth EV markers, genetically modifying these organisms, and identifying rigorous methodologies for in vitro and in vivo studies. Here, we outline best practices for those investigating the biology of helminth-derived EVs to complement the MISEV guidelines. We summarise community-agreed standards for studying EVs derived from this broad set of non-model organisms, raise awareness of issues associated with helminth EVs and provide future perspectives for how progress in the field will be achieved

Total antioxidant activity and trace elements in human milk: the first 4 months of breast-feeding

The content of many nutrients in breast milk are dependent on the nutritional status of the lactating woman. This is particularly true for fat and water-soluble vitamins, some of which have antioxidant properties. The aim of the study entertained herein was to evaluate the changes in total antioxidant status of human milk during the first 4 months of lactation, and to correlate such changes with the contents in specific antioxidant oligoelements (Cu, Zn, Mn and Se). Milk samples were collected from (31) lactating women recruited at the Service of Obstetrics of the Hospital de São João in Porto, after 1, 4, 8, 12 and 16 weeks after birth. The total antioxidant status (TAS) of human milk was measured by the Randox® commercial kit and trace metals by ICP-MS (inductively coupled plasma-mass spectrometry). The results found for TAS and oligoelements under study show a decrease in the concentration of these parameters from 7 days to 4 months of breast-feeding and significant correlations (p < 0.05) were found between TAS and Cu, Zn and Se (not Mn). The decreases of Cu, Zn and Se were also correlated, but not proportional between them, suggesting diverse excretion mechanisms for all. Between primipara and multipara women, a significant difference was found only for Cu and Zn concentrations at 7 days of lactation, but not for the other metals or TAS. With respect to the mother’s age, no correlation was found, either for trace metal concentrations or TAS

Therapeutic efficacy of TBC3711 in monocrotaline-induced pulmonary hypertension

Background: Endothelin-1 signalling plays an important role in pathogenesis of pulmonary hypertension. Although different endothelin-A receptor antagonists are developed, a novel therapeutic option to cure the disease is still needed. This study aims to investigate the therapeutic efficacy of the selective endothelin-A receptor antagonist TBC3711 in monocrotaline-induced pulmonary hypertension in rats. Methods: Monocrotaline-injected male Sprague-Dawley rats were randomized and treated orally from day 21 to 35 either with TBC3711 (Dose: 30 mg/kg body weight/day) or placebo. Echocardiographic measurements of different hemodynamic and right-heart hypertrophy parameters were performed. After day 35, rats were sacrificed for invasive hemodynamic and right-heart hypertrophy measurements. Additionally, histologic assessment of pulmonary vascular and right-heart remodelling was performed. Results: The novel endothelin-A receptor antagonist TBC3711 significantly attenuated monocrotaline-induced pulmonary hypertension, as evident from improved hemodynamics and right-heart hypertrophy in comparison with placebo group. In addition, muscularization and medial wall thickness of distal pulmonary vessels were ameliorated. The histologic evaluation of the right ventricle showed a significant reduction in fibrosis and cardiomyocyte size, suggesting an improvement in right-heart remodelling. Conclusion: The results of this study suggest that the selective endothelin-A receptor antagonist TBC3711 demonstrates therapeutic benefit in rats with established pulmonary hypertension, thus representing a useful therapeutic approach for treatment of pulmonary hypertension