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BackgroundCongenital Morgagni hernia (CMH) is a rare midline defect involving herniation of abdominal viscera into the thoracic cavity through triangular parasternal gaps in the diaphragm.MethodsThe medical records of three patients with CMH admitted to the Department of Pediatric Surgery at the Affiliated Hospital of Zunyi Medical University between 2018 and 2022 were retrospectively reviewed. Pre-operative diagnosis was based on chest x-ray, chest computerized tomography, and barium enema. All patients were treated with single-site laparoscopic ligation of the hernia sac.ResultsHernia repair was successful in all patients (males; age: 14 months, 30 months, 48 months). The average operative time for repair of a unilateral hernia was 20 ± 5 min. Volume of surgical blood loss was 2–3 ml. There was no damage to organs such as the liver or intestines, or to tissues such as the pericardium or the phrenic nerve. Patients were allowed a fluid diet 6–8 h after surgery, and remained on bed rest until 16 h after surgery. No postoperative complications occurred, and patients were discharged on postoperative Day 2 or 3. No symptoms or complications were noted during the 1–48 months of follow-up. Aesthetic outcomes were satisfactory.ConclusionsSingle-site laparoscopic ligation of the hernia sac provides pediatric surgeons a safe and effective technique for repair of CMH in infants and children. The procedure is straightforward, operative time and surgical blood loss are minimal, recurrence is unlikely, and aesthetic outcomes are satisfactory.

Copyright of Gaceta Médica de Caracas is the property of Academia Nacional de Medicina and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: To compare the survival rate of paclitaxel plus cisplatin (PC arm), paclitaxel plus gemcitabine (PG arm) and gemcitabine plus cisplatin (GC arm) in chemotherapy patients with non resectable lung cancer. Methods: This was a retrospective observational study to evaluate chemotherapy response among non resectable lung cancer patients with their survival at cancer center CMH, Dhaka since 01 July 2013 to 31 March 2015. One hundred fifty-four (154) non resectable lung cancer patients were randomly divided into three groups, 50 patients in PC arm, 51 patients in PG arm and 53 patients in GC arm. In PC arm paclitaxel 175 mg/m2 (day 1) with cisplatin 75mg/m2 (day 1), in PG arm Paclitaxel 175 mg/m2 (day 1) with gemcitabine 1000 mg/m2 (days 1 and 8) and in GC arm gemcitabine 1000 mg/m2 (days 1 and 8) with cisplatin 100mg/m2 (day 1). Results: Patients characteristics were similar between the three groups. The overall response rate was 40% in the PC arm,43.1% in the PG arm, 43.4% in the GC arm. The median survival time in PC arm was 8.5 months, in PG arm was 8.8 months, in GC arm was 9.2 months. The major side effect was myelosuppression which accounts 71% patients. The average treatment costs were 57% and 30% lower in PC arm as compared with GC and PG arm respectively. Conclusion: The median survival time, disease free survival time and 1-year survival rate in PC, PG, GC arms without significant difference. Treatment were well tolerable; quality of life parameter was mostly similar but paclitaxel with cisplatin was most cost effective than others chemotherapy regimen. [ABSTRACT FROM AUTHOR]

Electron Paramagnetic Resonance (EPR) spectroscopy coupled with spin traps/probes enables quantitative determination of reactive nitrogen and oxygen species (RNOS). Even with numerous studies using spin probes, the methodology has not been rigorously investigated. The autoxidation of spin probes has been commonly overlooked. Using the spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine (CMH), the present study has tested the effects of metal chelators, temperature, and oxygen content on the autoxidation of spin probes, where an optimized condition is refined for cell studies. The apparent rate of CMH autoxidation under this condition is 7.01 ± 1.60 nM/min, indicating low sensitivity and great variation of the CMH method and that CMH autoxidation rate should be subtracted from the generation rate of CMH-detectable oxidants (simplified as oxidants below) in samples. Oxidants in RAW264.7 cells are detected at an initial rate of 4.0 ± 0.7 pmol/min/106 cells, which is not considered as the rate of basal oxidants generation because the same method has failed to detect oxidant generation from the stimulation of phorbol-12-mysirate-13-acetate (PMA, 0.1 nmol/106 cells) in cells (2.5 ± 0.9 for PMA vs. 2.1 ± 1.5 pmol/min/106 cells for dimethyl sulfoxide (DMSO)-treated cells). In contrast, the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), which exhibits minimal autoxidation, reveals differences between PMA and DMSO treatment (0.26 ± 0.09 vs. −0.06 ± 0.12 pmol/min/106 cells), which challenges previous claims that spin probes are more sensitive than spin traps. We have also found that low temperature EPR measurements of frozen samples of CMH autoxidation provide lower signal intensity and greater variation compared to RT measurements of fresh samples. The current study establishes an example for method development of RNOS detection, where experimental details are rigorously considered and tested, and raises questions on the applications of spin probes and spin traps. Image 1 • Method development for the detection of reactive oxygen species. • Electron Paramagnetic Resonance coupled with spin probes and spin traps. • Autoxidation of spin probes must be considered. • Oxidant generation from RAW264.7 cells. • Low temperature measurements provide less intensity and greater variability. [ABSTRACT FROM AUTHOR]

Regenerative capacity in vital organs is limited by fibrosis propensity. Idiopathic pulmonary fibrosis (IPF), a progressive lung disease linked with aging, is a classic example. In this study, we show that in flow cytometry, immunoblots (IB) and in lung sections, FLIP levels can be regulated, in vivo and in vitro, through SIRT1 activity inhibition by CMH (4-(4-Chloro-2-methylphenoxy)-N-hydroxybutanamide), a small molecule that, as we determined here by structural biology calculations, docked into its nonhistone substrate Ku70-binding site. Ku70 immunoprecipitations and immunoblots confirmed our theory that Ku70-deacetylation, Ku70/FLIP complex, myofibroblast resistance to apoptosis, cell survival, and lung fibrosis in bleomycin-treated mice, are reduced and regulated by CMH. Thus, small molecules associated with SIRT1-mediated regulation of Ku70 deacetylation, affecting FLIP stabilization in fibrotic-lung myofibroblasts, may be a useful strategy, enabling tissue regeneration.

Polycystic kidney disease (PKD) is a hereditary autosomal dominant disorder that mainly affects Persian cats; it is an important cause of chronic kidney disease in this species. Hypertrophic cardiomyopathy (HCM) is the most common heart disease in cats, and there is evidence of a genetic origin in some breeds. Although neither of these disorders is rare in cats, according to our literature review, this is the first report of the concomitant occurrence of PKD and HCM in Persian cats in Brazil.

The soil bacterium Burkholderia terrae strain BS001 can interact with varying soil fungi, using mechanisms that range from the utilization of carbon/energy sources such as glycerol to the ability to reach novel territories in soil via co-migration with growing fungal mycelia. Here, we investigate the intrinsic properties of the B. terrae BS001 interaction with the basidiomycetous soil fungus Lyophyllum sp. strain Karsten. In some experiments, the ascomycetous Trichoderma asperellum 302 was also used. The hyphae of Lyophyllum sp. strain Karsten were largely hydrophilic on water-containing media versus hydrophobic when aerial, as evidenced by contact angle analyses (CA). Co-migration of B. terrae strain BS001 cells with the hyphae of the two fungi occurred preferentially along the - presumably hydrophilic - soil-dwelling hyphae, whereas aerial hyphae did not allow efficient migration, due to reduced thickness of their surrounding mucous films. Moreover, the cell numbers over the length of the hyphae in soil showed an uneven distribution, i.e. the CFU numbers increased from minima at the inoculation point to maximal numbers in the middle of the extended hyphae, then decreasing towards the terminal side. Microscopic analyses of the strain BS001 associations with the Lyophyllum sp. strain Karsten hyphae in the microcosms confirmed the presence of B. terrae BS001 cells on the mucous matter that was present at the hyphal surfaces of the fungi used. Cell agglomerates were found to accumulate at defined sites on the hyphal surfaces, which were coined ‘fungal-interactive’ hot spots. Evidence was further obtained for the contention that receptors for a physical bacterium-fungus interaction occur at the Lyophyllum sp. strain Karsten hyphal surface, in which the specific glycosphingolipid ceramide mono hexoside (CMH) plays an important role. Thus, bacterial adherence may be mediated by heterogeneously-distributed fungal-specific receptors, implying the CMH moieties. This study sheds light on the physical aspects of the B. terrae BS001 – L. sp strain Karsten interaction, highlighting heterogeneity along the hyphae with respect to hydrophobicity and the presence of potential anchoring sites.

Background: Congenital Morgagni hernia (CMH) is a rare midline defect involving herniation of abdominal viscera into the thoracic cavity through triangular parasternal gaps in the diaphragm., Methods: The medical records of three patients with CMH admitted to the Department of Pediatric Surgery at the Affiliated Hospital of Zunyi Medical University between 2018 and 2022 were retrospectively reviewed. Pre-operative diagnosis was based on chest x-ray, chest computerized tomography, and barium enema. All patients were treated with single-site laparoscopic ligation of the hernia sac., Results: Hernia repair was successful in all patients (males; age: 14 months, 30 months, 48 months). The average operative time for repair of a unilateral hernia was 20 ± 5 min. Volume of surgical blood loss was 2-3 ml. There was no damage to organs such as the liver or intestines, or to tissues such as the pericardium or the phrenic nerve. Patients were allowed a fluid diet 6-8 h after surgery, and remained on bed rest until 16 h after surgery. No postoperative complications occurred, and patients were discharged on postoperative Day 2 or 3. No symptoms or complications were noted during the 1-48 months of follow-up. Aesthetic outcomes were satisfactory., Conclusions: Single-site laparoscopic ligation of the hernia sac provides pediatric surgeons a safe and effective technique for repair of CMH in infants and children. The procedure is straightforward, operative time and surgical blood loss are minimal, recurrence is unlikely, and aesthetic outcomes are satisfactory., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Wang, Liu, Shu, Yin, Luo, Liu and Liu.)

The soil bacterium Burkholderia terrae strain BS001 can interact with varying soil fungi, using mechanisms that range from the utilization of carbon/energy sources such as glycerol to the ability to reach novel territories in soil via co-migration with growing fungal mycelia. Here, we investigate the intrinsic properties of the B. terrae BS001 interaction with the basidiomycetous soil fungus Lyophyllum sp. strain Karsten. In some experiments, the ascomycetous Trichoderma asperellum 302 was also used. The hyphae of Lyophyllum sp. strain Karsten were largely hydrophilic on water-containing media versus hydrophobic when aerial, as evidenced by contact angle analyses (CA). Co-migration of B. terrae strain BS001 cells with the hyphae of the two fungi occurred preferentially along the - presumably hydrophilic - soil-dwelling hyphae, whereas aerial hyphae did not allow efficient migration, due to reduced thickness of their surrounding mucous films. Moreover, the cell numbers over the length of the hyphae in soil showed an uneven distribution, i.e., the CFU numbers increased from minima at the inoculation point to maximal numbers in the middle of the extended hyphae, then decreasing toward the terminal side. Microscopic analyses of the strain BS001 associations with the Lyophyllum sp. strain Karsten hyphae in the microcosms confirmed the presence of B. terrae BS001 cells on the mucous matter that was present at the hyphal surfaces of the fungi used. Cell agglomerates were found to accumulate at defined sites on the hyphal surfaces, which were coined 'fungal-interactive' hot spots. Evidence was further obtained for the contention that receptors for a physical bacterium specific receptors, implying the CMH moieties. This study sheds light on the physical aspects of the B. terrae BS001 -- Lyophyllum sp. strain Karsten interaction, highlighting heterogeneity along the hyphae with respect to hydrophobicity and the presence of potential anchoring sites. [ABSTRACT FROM AUTHOR]

Copyright of Animal Genetic Resources is the property of Cambridge University Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revista de Investigaciones Veterinarias del Peru is the property of Universidad Nacional Mayor de San Marcos (UNMSM) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: In the 1990s, the variability of responses to human immunodeficiency virus (HIV) could only be tracked by phenotypic criteria such as the number of CD4T lymphocytes, the occurrence of opportunistic infection, the disease free survival without treatment. In 1996, the viral load is the leading phenotype for genetic studies. Ever since, thanks to a better understanding of the HIV infection pathophysiology, numerous studies helped to highlight the influence of genetic variability on inter-individual response to this virus. Among the genes having an impact, we can quote the following examples: CCR5, HLA-B and HLA-C genes. Practical applications of genetics in clinical medicine include search for HLA-B*57:01 before abacavir introduction. Recently, an eradicating treatment for HIV disease after bone marrow transplantation with a donor homozygote for a CCR5 gene non-functional variant (CCR5Δ32) has been reported. Interest in genetics of chronic viral infection is not specific to HIV. It has also been used on other viral diseases and it has gained a major place on the management of diseases. [Copyright &y& Elsevier]

Despite the causative role of oxidative stress in renal ischemia-reperfusion (I-R) injury effects of preservation solutions on reactive oxygen species (ROS) release have not been sufficiently evaluated. We compared the effects of most common solutions in kidney transplantation, University of Wisconsin (UW) and Histidine–Tryptophan–Ketoglutarate (HTK). ROS formation in isolated perfused rat kidney was detected by electron spin resonance spectroscopy using spin label 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine. Donor kidneys from Lewis rats were pretreated with saline (controls), in therapeutic groups, kidneys underwent 18 h of cold storage (CS) preserved by HTK or UW solution. Experimental protocol included a stabilization period followed by additional I-R. Kidneys preserved by HTK produced highest ROS values in the control period after CS, whereas levels in UW and control group did not vary significantly. A peak release induced by additional I-R was also significantly highest in HTK kidneys, and UW did not differ from controls. During reperfusion, levels in HTK exceeded control and UW values. Renal vascular resistance, caspase-3-activity, and tissue hydration were enhanced in HTK compared with UW group, whereas ATP concentration was less reduced in UW-preserved tissue. These data show the greater antioxidative potential of UW solution, which also attenuated organ impairment after CS in the early reperfusion period.Kidney International (2007) 71, 875–881. doi:10.1038/sj.ki.5002129; published online 21 February 2007 [ABSTRACT FROM AUTHOR]

Abstract: The pathogenesis of food allergy was, in the past, focused on atopy, IgE and auxiliary lymphocytes responsible for class switching. Nevertheless, some allergic reactions induced by foods do not involve IgE. Mechanisms of breaking tolerance and cell mechanisms at the level of the gut mucosa are now better understood. This analysis of the involvement of lymphocytes in food allergy will begin with comments on presentation of antigens in Peyer''s patches, followed by comments on a recognition mechanism involving surface receptors and regulation by chemokines. In association with intestinal immunity, regulatory T cells have a central role in the induction of immunization or tolerance to foods. [Copyright &y& Elsevier]

Copyright of Néphrologie & Thérapeutique is the property of John Libbey Eurotext Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In order to effectively perceive the huge diversity of antigenic determinants to which it is confronted, the immune system uses referring internal images from self. The major histocompatibility complex constitutes the main reference to self, essential to the operating system of T and NK lymphocytes. It is involved in shaping the T operating repertoire in the thymus, where each differentiating thymocyte, with its TCR interacting with the MHC-peptide self complexes exposed by thymic presenting cells, should answer to both questions: Is it really necessary (positive selection) Is not dangerous (negative selection)? Once in periphery, naive T lymphocytes will undergo an homeostatic control helping their survival through the same contacts between TCR and MHC-peptide self complex than those which allowed the thymic positive selection. In a more hypothetic way, it is possible that contact between a T lymphocyte and the rare foreign MHC-peptide complexes spread at the surface of antigen presenting cell, is not sufficient to initiate its activation. Some arguments exist to involve the MHC-peptide self complexes themselves in the activation process.Finally, the MHC also constitutes a quality referential for the NK lymphocytes. When a somatic cell, infected by a virus or transformed, repress the expression of one or more of its class I HLA alleles, this absence of the self is perceived by the NK lymphocytes which proceed to its elimination through cytolysis. This disposition to sanction the non-self is also used for therapeutic purpose in the case of a non HLA identical allogenic hematopoi¨etic stem cells graft. [Copyright &y& Elsevier]

Function of T and natural killer (NK) lymphocytes is tightly controlled by the balance of activating and inhibitory signals. NK receptors belong to different families: KIRs (“Killer cell Immunoglobulin-like Receptor”) and ILTs (“Immunoglobulin-like Transcript”), mainly inhibitory which binds to HLA class I alleles; C-type lectin NK receptors such as CD94/NKG2A which is inhibitory and binds to HLA-E ; NCR (“Natural Cytotoxicity Receptors”) which directly activate NK cells. These include molecules NKp30, NKp44, NKp46 et NKG2D. Cellular stress (viral and bacterial infections, tumours) may modulate NK function by different mechanisms: decrease in HLA class I molecules expression resulting in the lack of engagement of the inhibitory receptors and ultimately NK cell activation; modulation of CD94/NKG2A inhibitory function through expression of peptides presented by HLA-E as for instance from heat shock proteins; NK activation through NCR expression. Among these, NKG2D is an activating receptor expressed by NK cells and subsets of αβ and γδ and T cells. Major NKG2D ligands in humans are MIC (“MHC class I related”) molecules which are stress-inducible during a viral (CMV) or bacterial infection (M. tuberculosis, E. coli). They may also be expressed by tumors. Therefore, they could play a role in activating NK and/or T lymphocyte responses in these conditions. [Copyright &y& Elsevier]

It is important for the physician to fully understand the basic phenomena of histocompatibility and the specialized functions of a group of genes denominated major histocompatibility complex (MHC) which encode what constitutes the human leucocyte antigen (HLA) system. The HLA system is the most polymorphic known in humans. There are two classes of HLA antigens, class I includes HLA-A, -B and -C. Class II includes HLA-DR. -DQ and -DP. The function of the HLA system is to recognize peptides and exhibit them on the surface of antigen presenting cells, like macrophages, in order to be reviewed by T lymphocytes which will differentiate self from non-self antigens. Due to its extensive polymorphism, HLA antigens themselves constitute antigens capable of activating a powerful immune reaction. HLA class I molecules are also known as the classic transplant antigens, as they were the first discovered when response to human allgrafting was studied. Class II molecules, although discovered later, are in general the most important to match for a successful transplant. Several immunogenetics techniques for studying tissue identity are available in order to ensure full or adequate histocompatibility. These assays can be serologic, such as the classic microlymphocytotoxicity assay, genotypic, employing the polymerase chain reaction, and tissue culture techniques, such as the mixed lymphocyte reaction. In conclusion, adequate histocompatibility between a graft receptor and his or her donor, certified through HLA tissue typing, is essential to guarantee the long-term functioning of the allograft, and the optimal survival of the receptor. [ABSTRACT FROM AUTHOR]

Regenerative capacity in vital organs is limited by fibrosis propensity. Idiopathic pulmonary fibrosis (IPF), a progressive lung disease linked with aging, is a classic example. In this study, we show that in flow cytometry, immunoblots (IB) and in lung sections, FLIP levels can be regulated, in vivo and in vitro, through SIRT1 activity inhibition by CMH (4-(4-Chloro-2-methylphenoxy)-N-hydroxybutanamide), a small molecule that, as we determined here by structural biology calculations, docked into its nonhistone substrate Ku70-binding site. Ku70 immunoprecipitations and immunoblots confirmed our theory that Ku70-deacetylation, Ku70/FLIP complex, myofibroblast resistance to apoptosis, cell survival, and lung fibrosis in bleomycin-treated mice, are reduced and regulated by CMH. Thus, small molecules associated with SIRT1-mediated regulation of Ku70 deacetylation, affecting FLIP stabilization in fibrotic-lung myofibroblasts, may be a useful strategy, enabling tissue regeneration. [ABSTRACT FROM AUTHOR]

Soon after the pandemic, numerous publications described cases of neurological disorders associated with the SARS-CoV-2 infection. The range of neurological symptoms is becoming increasingly more extensive as the pandemic progresses. However, it is not yet well established whether the manifestations are due to direct viral damage to the nervous system or indirect consequences of the infection. This review presents an inventory of the biochemical markers studied in the context of neurological disorders related to SARS-CoV-2. By reflecting various physiopathological mechanisms, these biomarkers allow both a better understanding of the pathophysiology of Covid-19 and a contribution to the diagnosis of neurologic troubles; they could participate in the prognostic evaluation of patients.

Objectives: To assess whether the gastroparesis cardinal symptom index (GCSI), or any individual symptom, is associated with delayed gastric emptying in children, and to assess understanding of symptoms associated with delayed gastric emptying., Study Design: Fifty children (36 F), 5-18 years of age, undergoing gastric emptying scintigraphy (GES) at Lurie Children's Hospital in Chicago, Illinois, completed Likert-type GCSI and symptom comprehension questionnaires. Correlation of GES results (normal or abnormal) with questionnaire results using the Wilcoxon rank sum test., Results: Seventy percent of subjects had a normal GES. Children reported understanding most terms of GCSI (average score 2.59, range 0-3). The GCSI was not associated with delayed gastric emptying. Nausea was associated with delayed gastric emptying only (numerical P = .04, word P = .02). Results were not altered when poorly understood terms were excluded., Conclusions: The GCSI is not associated with delayed gastric emptying in children. Lack of association does not seem to be related to lack of understanding. Nausea alone was the only symptom that showed an association with delayed gastric emptying on GES., (Published by Mosby, Inc.)

Current estimates and projections suggest that the burden of cardiovascular diseases (CVDs), diabetes and related risk factors in African countries is important, somewhat unique and rapidly growing. Various segments of the population are affected; however, the group mostly affected is young adults residing in urban areas, and increasingly those in the low socioeconomic strata. The African milieu/environment is compounded by weak health systems, which are unable to cope with the looming double burden of communicable and chronic non-communicable diseases. This review discusses the economic and developmental challenges posed by CVDs and diabetes in countries in Africa. Using several lines of evidence, we demonstrate that the cost of care for major CVDs and diabetes is beyond the coping capacities of individuals, households, families and governments in most African countries. We have reviewed modeling studies by the International Diabetes Federation (IDF) and other major international agencies on the current and projected impact that CVDs and diabetes have on the economy and development of countries in the region. Locally, appropriate strategies to limit the impact of the conditions on the economies and development of countries in Africa are suggested and discussed. These include monitoring diseases and risk factors, and primordial, primary and secondary preventions implemented following a life-course perspective. Structural, logistic, human capacity and organizational challenges to be surmounted during the implementations of these strategies will be reviewed., (© 2013.)

We studied the altered molecular species of lipids in brain and liver tissues, and fibroblasts from patients with Zellweger syndrome (ZS). ZS cerebellum samples contained a higher amount of sphingomyelin with shorter chain fatty acids compared to that in normal controls. The amount of phosphatidylethanolamine (PE) was less than half of that in controls, with the absence of the PE-type of plasmalogen. Gangliosides were accumulated in the brains and fibroblasts of ZS patients. To investigate whether or not impaired beta-oxidation of very long chain fatty acids and/or plasmalogen synthesis affects glycolipids metabolism, RNAi of peroxisomal acylCo-A oxidase (ACOX1) and glyceronephosphate O-acyltransferase (GNPAT) was performed using cultured neural cells. In neuronal F3-Ngn1 cells, ACOX1 and GNPAT silencing up-regulated ceramide galactosyltransferase (UGT8) mRNA expression, and down-regulated UDP-glucose ceramide glucosyltransferase (UGCG). These results suggest that both impaired beta-oxidation of very long chain fatty acids and plasmalogen synthesis affect glycolipid metabolism in neuronal cells., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Pain from cancer can be severe, difficult to treat, and greatly diminishes patients' quality of life. It is therefore important to gain new information on the mechanisms of cancer pain and develop new treatment strategies. We have used a murine model of bone cancer pain to investigate underlying peripheral neural mechanisms and novel treatment approaches. In this model, implantation of fibrosarcoma cells into and around the calcaneous bone produces mechanical and thermal hyperalgesia in mice. C-fiber nociceptors in tumor-bearing mice develop spontaneous ongoing activity and sensitization to thermal stimuli. However, it is unclear whether sensitization of nociceptors to mechanical stimuli underlies the mechanical hyperalgesia seen in tumor-bearing mice. We therefore examined responses of C-fiber nociceptors to suprathreshold mechanical stimuli in tumor-bearing mice and found they did not differ from those of C-nociceptors in control mice. Thus, sensitization of C-fiber nociceptors to mechanical stimulation does not appear to underlie tumor-evoked mechanical hyperalgesia in this murine model of bone cancer pain. We also examined the effect of the non-selective cannabinoid receptor agonist, WIN 55,212-2, on spontaneous activity and responses evoked by mechanical stimuli of C-fiber nociceptors innervating the tumor-bearing paw. Selective CB1 and CB2 antagonists were administered to determine the contribution of each receptor subtype to the effects of WIN 55,212-2. Intraplantar administration of WIN 55,212-2 attenuated spontaneous discharge and responses evoked by mechanical stimulation of C-fiber nociceptors. These effects were inhibited by prior intraplantar administration of selective CB1 (AM281) or CB2 (AM630) receptor antagonists but not by vehicle. These results indicate that activation of either CB1 or CB2 receptors reduced the spontaneous activity of C-fiber nociceptors associated with tumor growth as well as their evoked responses. Our results provide further evidence that activation of peripheral cannabinoid receptors may be a useful target for the treatment of cancer pain., (Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.)