Plant materials for gastrointestinal diseases used in Chawang District, Nakhon Si Thammarat Province, Thailand

Publication date: 24 December 2016
Source:Journal of Ethnopharmacology, Volume 194
Author(s): Oratai Neamsuvan, Thanchanok Phumchareon, Wanisa Bunphan, Wayanan Kaosaeng
Ethnopharmacological relevanceIn Thailand, gastrointestinal diseases have occurred since the past, consequently healers know well how to use herbs for treatment. Currently, some groups of Thai people continue to be interested in treating diseases by herbs. Therefore, the aims of this study were to (1) compile a list of species of medicinal plants and their source, (2) document the diseases treated and their frequency of citation, (3) record the parts used, methods of preparation and route of administration of traditional medicines, and (4) compare the folk knowledge to that in other relevant reports.Materials and methodsTen folk healers were included in the study. Semi-structured interviews were used to compile data, namely plant parts used, preparation, route of administration and properties. The data were analyzed by interpretation and descriptive statistics.ResultsSixty-two species in 28 families were identified. The most used plants (11 species) were grouped in Zingiberaceae. The highest level of relative frequency of citation (RFC) was found in Zingiber officinale Roscoe (1.0). Most plants were applied for treating constipation. Powder was the most common preparation form of folk drug. A total of 174 use lists were recorded, however, more than two thirds were reported as new uses in this study.ConclusionA literature review revealed that the remaining 37 species for pharmacological activities and 42 species for toxicity should be further studied to validate the folk use of these medicinal resource.

Graphical abstract

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Ginsenosides attenuate d-galactose- and AlCl3-inducedspatial memory impairment by restoring the dysfunction of the neurotransmitter systems in the rat model of Alzheimer's disease

Publication date: 24 December 2016
Source:Journal of Ethnopharmacology, Volume 194
Author(s): Yan Zhang, Zifeng Pi, Fengrui Song, Zhiqiang Liu
Ethnopharmacological relevancePanax ginseng C.A.Mey. is a traditional Chinese herbal medicine, which has been used to treat Alzheimer's disease (AD) for thousands of years. Ginsenoside is one of the major compounds found in P. ginseng. This study aimed to explore the attenuation of spatial memory impairment by ginsenosides and its correlation with restoring the dysfunction of the neurotransmitter systems in AD model rats to understand the mechanism underlying the anti-AD effect of P. ginseng.Materials and methodsIn this study, the AD model was established by combining d-galactose (d-gal) with AlCl3 (Al) for 60 days. From day 30, the ginsenosides group was intragastrically administered with ginsenosides for 30 days. The ethology of rats was tested through the Morris water maze test(MWM). Histopathological changes in the hippocampus of rats were observed through hematoxylin and eosin staining. The expressions of amyloid β peptide (Aβ) and phospho-tau (p-tau) in the hippocampus and cortex of rats were detected by immunohistochemistry. A liquid chromatography–mass spectrometry assay was used to measure neurotransmitter concentrations in the hippocampus, cortex, and blood.ResultsGinsenosides could significantly decrease the escape latency time and the average latency time in the place navigation test and increase the times of crossing the platform area, the percentage of residence time, and the distance in the original platform quadrant in the spatial probe test. Ginsenosides could repair the damage of the hippocampus and reduce the expressions of Aβ and p-tau. Ginsenosides could also increase γ-aminobutyric acid, acetylcholine, and dopamine levels and decrease glutamate and aspartic acid levels in the hippocampus and cortex and increase glycine and serotonin levels in the blood.ConclusionsAfter effectively administrated, ginsenosides attenuate d-gal- and Al-induced spatial memory impairment. The possible mechanism of the beneficial effect is restoring the dysfunction of various neurotransmitters.

Graphical abstract

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The antioxidant transcription factor Nrf2 contributes to the protective effect of mild thermotolerance (40°C) against heat shock-induced apoptosis

Publication date: October 2016
Source:Free Radical Biology and Medicine, Volume 99
Author(s): Audrey Glory, Diana A. Averill-Bates
The exposure of cells to low doses of stress induces adaptive survival responses that protect cells against subsequent exposure to toxic stress. The ability of cells to resist subsequent toxic stress following exposure to low dose heat stress at 40°C is known as mild thermotolerance. Mild thermotolerance involves increased expression of heat shock proteins and antioxidants, but the initiating factors in this response are not understood. This study aims to understand the role of the Nrf2 antioxidant pathway in acquisition of mild thermotolerance at 40°C, and secondly, whether the Nrf2 pathway could be involved in the protective effect of thermotolerance against heat-shock (42°C)-induced apoptosis. During cell preconditioning at 40°C, protein expression of the Nrf2 transcription factor increased after 15–60min. In addition, levels of the Nrf2 targets MnSOD, catalase, heme oxygenase-1, glutamate cysteine ligase and Hsp70 increased at 40°C. Levels of these Nrf2 targets were enhanced by Nrf2 activator oltipraz and decreased by shRNA targeting Nrf2. Levels of pro-oxidants increased after 30–60min at 40°C. Pro-oxidant levels were decreased by oltipraz and increased by knockdown of Nrf2. Increased Nrf2 expression and catalase activity at 40°C were inhibited by the antioxidant PEG-catalase and by p53 inhibitor pifithrin-α. These results suggest that mild thermotolerance (40°C) increases cellular pro-oxidant levels, which in turn activate Nrf2 and its target genes. Moreover, Nrf2 contributes to the protective effect of thermotolerance against heat-shock (42°C)-induced apoptosis, because Nrf2 activation by oltipraz enhanced thermotolerance, whereas Nrf2 knockdown partly reversed thermotolerance. Improved knowledge about the different protective mechanisms that mild thermotolerance can activate is crucial for the potential use of this adaptive survival response to treat stress-related diseases.



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Sensitive detection and estimation of cell-derived peroxynitrite fluxes using fluorescein-boronate

Publication date: Available online 15 September 2016
Source:Free Radical Biology and Medicine
Author(s): Natalia Rios, Lucía Piacenza, Madia Trujillo, Alejandra Martínez, Verónica Demicheli, Carolina Prolo, María Noel Álvarez, Gloria V. López, Rafael Radi
The specific and sensitive detection of peroxynitrite (ONOO^‒/ONOOH) in biological systems is a great challenge due to its high reactivity towards several biomolecules. Herein, we validated the advantages of using fluorescein-boronate (Fl-B) as a highly sensitive fluorescent probe for the direct detection of peroxynitrite under biologically-relevant conditions in two different cell models. The synthesis of Fl-B was achieved by a very simply two-step conversion synthetic route with high purity (> 99 %) and overall yield (∼ 42%). Reactivity analysis of Fl-B with relevant biological oxidants including hydrogen peroxide (H2O2), hypochlorous acid (HOCl) and peroxynitrite were performed. The rate constant for the reaction of peroxynitrite with Fl-B was 1.7 x 10⁶ M^-1s^-1, a million times faster than the rate constant measured for H2O2 (k = 1.7 M^-1s^-1) and 2,700 faster than HOCl (6.2 x 10² M^-1s^-1) at 37° C and pH 7.4. The reaction of Fl-B with peroxynitrite was significant even in the presence of physiological concentrations of CO2, a well-known peroxynitrite reactant. Experimental and simulated kinetic analyses confirm that the main oxidation process of Fl-B takes place with peroxynitrite itself via a direct bimolecular reaction and not with peroxynitrite-derived radicals. Fl-B was successfully applied for the detection of endogenously- generated peroxynitrite by endothelial cells and in macrophage-phagocyted parasites. Moreover, the generated data allowed estimating the actual intracellular flux of peroxynitrite. For instance, ionomycin-stimulated endothelial cells generated peroxynitrite at a rate of ∼ 0.1 μM s^-1, while immunostimulated macrophages do so in the order of ∼ 1 μM s^-1 inside T. cruzi-infected phagosomes. Fl-B revealed not to be toxic in concentrations up to 1 mM for 24 h. Cellular peroxynitrite detection was achieved by conventional laboratory fluorescence-based methods including flow cytometry and epi-fluorescence microscopy. Fl-B was shown to be more sensitive than the coumarin boronate due to a higher molar absorption coefficient and quantum yield. Overall, our results show that Fl-B is a kinetically selective and highly sensitive probe for the direct detection of cell-derived peroxynitrite.



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Interactions between neurokinin B and kisspeptin in mediating estrogen feedback in healthy women

The Journal of Clinical Endocrinology &Metabolism, Early Release.


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Diabetic Ketoacidosis without Diabetes

The Journal of Clinical Endocrinology &Metabolism, Early Release.


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Adhesion G-protein coupled receptor G1 (ADGRG1/GPR56) and pancreatic β-cell function

The Journal of Clinical Endocrinology &Metabolism, Early Release.


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Impact of completion axillary lymph node dissection in patients with breast cancer and isolated tumour cells or micrometastases in sentinel nodes

Publication date: November 2016
Source:European Journal of Cancer, Volume 67
Author(s): G. Houvenaeghel, J.M. Boher, F. Reyal, M. Cohen, J.R. Garbay, J.M. Classe, R. Rouzier, S. Giard, C. Faure, H. Charitansky, C. Tunon de Lara, E. Daraï, D. Hudry, P. Azuar, P. Gimbergues, R. Villet, P. Sfumato, E. Lambaudie
BackgroundOmission of completion axillary lymph node dissection (ALND) is a standard practice in patients with breast cancer (BC) and negative sentinel nodes (SNs) but has shown insufficient evidence to be recommended in those with SN invasion.MethodsA retrospective analysis of a cohort of patients with BC and micrometastases (Mic) or isolated tumour cells (ITCs) in SN. Factors associated with ALND were identified, and patients with ALND were matched to patients without ALND. Overall survival (OS) and recurrence-free survival (RFS) were estimated in the overall population, in Mic and in ITC cohorts.FindingsAmong 2009 patients analysed, 1390 and 619 had Mic and ITC in SN, respectively. Factors significantly associated with ALND were SN status, histological type, age, number of SN harvested and absence of adjuvant chemotherapy. After a median follow-up of 60.4 months, ALND omission was independently associated with reduced OS (hazard ratio [HR] 2.41, 90 confidence interval [CI] 1.36–4.27, p = 0.0102), but not with increased RFS (HR 1.21, 90 CI 0.74–2.0, p = 0.52) in the overall population. In matched patients, the increased risk of death in case of ALND omission was found only in the Mic cohort (HR 2.88, 90 CI 1.46–5.69), not in the ITC cohort. The risk of recurrence was also significantly increased in the subgroup of matched Mic patients (HR 1.56, 90 CI 0.90–2.73).InterpretationA separate analysis of Mic and ITC groups, matched for the determinants of ALND, suggested that patients with Mic had increased recurrence rates and shorter OS when ALND was not performed. Our results are consistent with those of previous studies for patients with ITC but not for those with Mic. Randomised controlled clinical trials are still warranted to show with a high level of evidence if ALND can be safely omitted in patients with micrometastatic disease in SN.



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Neutrophil-to-lymphocyte ratio as a prognostic marker in locally advanced nasopharyngeal carcinoma: A pooled analysis of two randomised controlled trials

Publication date: November 2016
Source:European Journal of Cancer, Volume 67
Author(s): Melvin Lee Kiang Chua, Sze Huey Tan, Grace Kusumawidjaja, Ma Than Than Shwe, Shie Lee Cheah, Kam Weng Fong, Yoke Lim Soong, Joseph Tien Seng Wee, Terence Wee Kiat Tan
PurposeTo assess the prognostic value of neutrophil-to-lymphocyte ratio (NLR) in patients with International Union Against Cancer (UICC)–staged III/IVA,B nasopharyngeal carcinoma (NPC), who were enrolled into two randomised controlled trials of concurrent/adjuvant chemotherapy when added to radiotherapy (SQNP01), and induction chemotherapy when added to chemoradiotherapy (NCC0901).Material and methodsA post hoc analysis of pooled cohorts from SQNP01 (N = 221) and NCC0901 (N = 172) was performed. We employed a threshold of pre-treatment NLR = 3.0 (median) to stratify patients. Survival outcomes were compared using log-rank test. Multivariable Cox regression analyses were performed to assess association between NLR and overall survival (OS), disease-free survival (DFS), distant metastasis–free survival (DMFS), and locoregional recurrence–free survival (LRFS).ResultsHigh NLR (≥3.0) was associated with advanced T-status (p = 0.002), N-status (p = 0.002), overall UICC stage (p = 0.004), and high pre-treatment Epstein–Barr virus DNA titre (p = 0.001). High NLR was not associated with OS (0.94 [0.67–1.32], p = 0.7), DFS (0.98 [0.73–1.33], p = 0.9), DMFS (1.02 [0.66–1.57], p = 0.9), and LRFS (1.37 [0.84–2.22], p = 0.2) on univariable and multivariable analyses, while conventional clinical indices (T-status, N-status, and overall UICC stage) were prognostic of clinical outcomes. High NLR also did not predict for a treatment effect with the experimental arms in both trials.ConclusionOur pooled analyses that were confined to a homogenous patient population of locally advanced NPC do not suggest that NLR adds prognostic value to conventional clinical indices in identifying patients with unfavourable disease.



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Associations between childhood height and morphologically different variants of melanoma in adulthood

Publication date: November 2016
Source:European Journal of Cancer, Volume 67
Author(s): Kathrine Damm Meyle, Michael Gamborg, Lisbet Rosenkrantz Hölmich, Jennifer Lyn Baker
Aim of the studyMelanoma subtypes have different aetiological characteristics. Child height is positively associated with adult melanoma; however, a clarification of associations with specific melanoma variants is necessary for an improved understanding of risk factors underlying the histologic entities. This study investigated associations between childhood height and future development of cutaneous melanoma variants.MethodA cohort study of 316,193 individuals from the Copenhagen School Health Records Register, with measured heights at ages 7–13 years who were born from 1930 to 1989. Melanoma cases were identified via linkage to the national Danish Cancer Registry and subdivided into subtypes. Cox proportional hazards regressions were performed.ResultsA total of 2223 cases of melanoma distributed as 60% superficial spreading melanoma (SSM), 27.5% melanoma not otherwise specified (NOS), 8.5% nodular melanoma (NM), and 2% lentigo maligna melanoma (LMM). The remaining rare melanoma forms were not analysed. Childhood height was positively and significantly associated with SSM, melanoma NOS, and NM, but not LMM, in adulthood. Per height z-score at age 13 years, the hazard ratios were 1.20 (95% confidence intervals [CI]: 1.13–1.27) for SSM, 1.19 (95% CI: 1.09–1.29) for melanoma NOS, and 1.21 (95% CI: 1.04–1.41) for NM. Further, growth patterns were linked to the melanoma variants with persistently tall children having an increased risk of developing SSM, melanoma NOS, or NM.ConclusionChildhood height is positively associated with the majority of the melanoma variants. These results suggest that the underlying processes contributing to childhood height and growth patterns interconnect early-life events with the predisposition to melanomagenesis in adulthood.



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Retrolaminar Migration of Intraocular Silicone Oil.

Background: Migration of intravitreal silicone to the retrolaminar optic nerve was detected pathologically in 1983, symptomatic migration to the subarachnoid space of the optic nerve was reported in 1994, and asymptomatic intraventricular silicone was first seen radiographically in 1999. Since then, little advance has been made in understanding this phenomenon despite numerous case reports. Although some authors have restricted their attention to cases of intraventricular silicone, we believe that these represent part of a clinical spectrum and that all cases with retrolaminar silicone should be considered. The pathophysiology of silicone migration may have significant implications for the management of patients after vitrectomy. Evidence Acquisition: Two patients were evaluated by the authors. An internet-based literature review was conducted, beginning with the key search terms "intraventricular, intracranial, subarachnoid, or optic nerve silicone," and "complications of vitrectomy or intravitreal silicone." Further searches cascaded from the initial search results. An additional 24 cases of retrolaminar migration of silicone oil were found and summarized. The relevant anatomy and pathophysiology were reviewed, with attention to additional information from enucleation studies, as well as to gaps in the current understanding of this process. Results: Retrolaminar migration of silicone oil may be more common than previously thought, especially in at-risk patient groups, and may be associated with visual and neurologic symptoms. Some impressions regarding the cause and significance of this syndrome seem incorrect. Although this process is likely linked to postoperative elevations of intraocular pressure, the exact mechanisms of silicone entry into the subarachnoid space remain undefined. A number of anatomic factors may influence the movement of silicone from the orbit and in the various compartments of the subarachnoid space and ventricular system, resulting in variability of clinical presentations and radiologic findings. Implications for clinical decision making and directions for further research are discussed. Conclusion: Greater awareness on the part of treating physicians, systematic study of at-risk populations, and advances in imaging technology will allow further insight into this phenomenon. (C) 2016 by North American Neuro-Ophthalmology Society

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Avoiding Clinical Misinterpretation and Artifacts of Optical Coherence Tomography Analysis of the Optic Nerve, Retinal Nerve Fiber Layer, and Ganglion Cell Layer.

Background: Optical coherence tomography (OCT) has become an important tool for diagnosing optic nerve disease. The structural details and reproducibility of OCT continues to improve with further advances in technology. However, artifacts and misinterpretation of OCT can lead to clinical misdiagnosis of diseases if they go unrecognized. Evidence Acquisition: A literature review using PubMed combined with clinical and research experience. Results: We describe the most common artifacts and errors in interpretation seen on OCT in both optic nerve and ganglion cell analyses. We provide examples of the artifacts, discuss the causes, and provide methods of detecting them. In addition, we discuss a systematic approach to OCT analysis to facilitate the recognition of artifacts and to avoid clinical misinterpretation. Conclusions: While OCT is invaluable in diagnosing optic nerve disease, we need to be cognizant of the artifacts that can occur with OCT. Failure to recognize some of these artifacts can lead to misdiagnoses and inappropriate investigations. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially. (C) 2016 by North American Neuro-Ophthalmology Society

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Obesity and Weight Loss in Idiopathic Intracranial Hypertension: A Narrative Review.

Background: Most patients with idiopathic intracranial hypertension (IIH) are obese. Weight loss is felt to be an important factor in improving IIH. The mechanism by which weight loss leads to a reduction in elevated intracranial pressure is unclear. Evidence from prospective studies evaluating the role of weight loss in IIH is lacking. Evidence Acquisition: We performed a detailed review of the published literature regarding the association of IIH and obesity, including proposed pathogenetic mechanisms, and the effect of weight loss and weight-loss interventions in IIH. References were identified by searching PubMed with the terms idiopathic intracranial hypertension and weight loss. Additional citations were found in the identified references. Results: Over 90% of IIH patients are obese or overweight. The risk of IIH increases as a function of body mass index (BMI) and weight gain over the preceding year. The risk of IIH-induced vision loss also increases with increasing BMI, especially with BMI >40 kg/m2. Several mechanisms have been proposed linking obesity to the development of IIH but the pathophysiology remains unknown. Published studies and clinical observations strongly support weight loss as an effective treatment, although there are no prospective controlled trials. Weight loss in the range of 6%-10% often leads to IIH remission. Weight loss of >=5% at 1 year is achieved in roughly 50%-70% of patients if they are enrolled in a high-intensity lifestyle modification program and in 20%-35% of patients if they direct their own weight loss. Weight is typically regained over 1-3 years but about a third of patients maintain >=5% weight loss over the long term. Patients treated initially with lifestyle modification therapy show a modest persisting benefit over self-directed patients. Selected commercial weight loss programs also may improve long-term maintenance of weight loss. New antiobesity drugs significantly improve the proportion of obese patients who have >=5% loss of weight at 1 year. Conclusions: Obesity is an important contributing factor for the development of IIH, although the pathophysiological mechanism linking obesity to IIH is unknown. The risk of developing IIH and associated visual loss increases with increasing BMI. Weight loss is an effective treatment for IIH. Long-term maintenance of initial weight loss is helped modestly by lifestyle modification programs and possibly by selected commercial weight loss programs. New antiobesity drugs may provide further options for IIH therapy in the future. (C) 2016 by North American Neuro-Ophthalmology Society

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Re-Treatment With Ethambutol After Toxic Optic Neuropathy.

There are no data in the literature regarding the safety of re-treatment with ethambutol for recurrent mycobacterial infection after prior ethambutol-induced optic neuropathy. We describe a patient who developed optic neuropathy attributed to ethambutol, recovered fully after drug withdrawal, and tolerated a 14-month long re-treatment 10 years later without developing recurrent optic neuropathy. (C) 2016 by North American Neuro-Ophthalmology Society

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IgG4 Disease: Is It or Isn't It?.

No abstract available

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Low-level laser therapy reduces the fatigue index in the ankle plantar flexors of healthy subjects

Abstract

Low-level laser therapy (LLLT) has been suggested as a resource capable of increasing resistance to fatigue and enhancing muscle performance through its metabolic and photochemical effects. This study evaluated the immediate effects of the application of LLLT on neuromuscular performance of the plantar ankle flexors in healthy subjects through a fatigue-induced protocol. This is a randomized controlled clinical trial, attended by 60 young and physically active volunteers of both genders. The subjects were randomly assigned into three groups, control, placebo, and laser, and underwent a preliminary evaluation of the isokinetic performance of plantar flexors and electromyographic activity of the soleus muscle to ensure homogeneity between groups. After the application of the respective intervention protocols, participants were induced to fatigue by performing 100 isokinetic concentric contractions of ankle plantar flexors at a speed of 90°/s. The dynamometric fatigue index (DFI) and median frequency were recorded during the fatigue protocol for comparison between groups. The group receiving the laser application showed significantly lower dynamometric fatigue index (p = 0.036) when compared to control and placebo groups. In relation to the median frequency during the fatigue test, there was a decrease in all groups, however with no differences between them. We suggest that LLLT being applied prior to exercise can reduce the fatigue index in the ankle plantar flexors of healthy subjects.

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Photobiomodulation therapy reduces apoptotic factors and increases glutathione levels in a neuropathic pain model

Abstract

Neuropathic pain (NP) is caused by damage to the nervous system due to reactive oxygen spices (ROS) increase, antioxidants reduction, ATP production imbalance, and induction of apoptosis. In this investigation, we applied low-level laser 660 nm (photobiomodulation therapy) as a new strategy to modulate pain. In order to study the effects of photobiomodulation therapy (660 nm) on NP, chronic constriction injury (CCI) model was selected. Low-level laser of 660 nm was used for 2 weeks. Thermal and mechanical hyperalgesia were measured before and after surgery on days 7 and 14, respectively. Paw withdrawal thresholds were also evaluated. Expression of p2x3, Bax, and bcl2 protein was measured by western blotting. The amount of glutathione (GSH) was measured in the spinal cord by continuous spectrophotometric rate determination method. The results are presented as mean ± SD. Statistical analysis of data was carried out using SPSS 21. CCI decreased the pain threshold, 2-week photobiomodulation therapy significantly increased mechanical and thermal threshold, decreased P2X3 expression (p < 0.001), and increased bcl2 expression (p < 0.01), but it was not effective on the Bax expression. We speculated that although photobiomodulation therapy increased ROS generation, it increased antioxidants such as GSH. Increase in bcl2 is another mitochondrial protection mechanism for cell survival and that pain relief and decrease in P2X3 expression confirm it.

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Increase in the nitric oxide release without changes in cell viability of macrophages after laser therapy with 660 and 808 nm lasers

Abstract

The aim of this study was to evaluate the influence of low-level laser therapy (LLLT) with different parameters and wavelengths on nitric oxide (NO) release and cell viability. Irradiation was performed with Ga-Al-As laser, continuous mode and wavelengths of 660 and 808 nm at different energy and power densities. For each wavelength, powers of 30, 50, and 100 mW and times of 10, 30, and 60 s were used. NO release was measured using Griess reaction, and cell viability was evaluated by mitochondrial reduction of bromide 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) to formazan. LLLT promoted statistically significant changes in NO release and MTT value only at the wavelength of 660 nm (p < 0.05). LLLT also promoted an increase in the NO release and cell viability when the energy densities 64 (p = 0.04) and 214 J/cm² (p = 0.012), respectively, were used. LLLT has a significant impact on NO release without affecting cell viability, but the significance of these findings in the inflammatory response needs to be further studied.

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Modulation of nociception by medial pre-optic area orexin a receptors and its relation with morphine in male rats

Publication date: Available online 15 September 2016
Source:Brain Research Bulletin
Author(s): Amir Hossein Emam, Naeimeh Hajesfandiari, Siamak Shahidi, Alireza Komaki, Maziar Ganji, Abdolrahman Sarihi
IntroductionRecent studies have shown that medial pre-optic area (MPOA) of hypothalamus are involved in nociception. Orexin A (hypocretin 1) has been found to have numerous applications including pain modulation. However, the role of orexin A receptors in the MPOA on the nociception has not been yet studied. Therefore, the aim of the present study is to investigate the effect of orexin A microinjection on MPOA on the nociception transmission and morphine induced analgesia in adult male rats.MethodsUsing stereotaxic surgery, a cannula was implanted at a site 1mm above the MPOA in the anesthetized rats. After the recovery period, tail-flick (TF) latency was measured as 0, 15, 30, 45 and 60min following the onset of two experimental protocols. Two experiments were carried out. Experiment 1: The male rats received intra-MPOA of 25, 100, 1000, 10000pmol/0.5μl orexin A or 0.5μl of aCSF (control, just 5min before the TF assay. Experiment 2: The aim of this experiment was to examine the effect of orexin microinjection into MPOA on morphine analgesia (3mg/kg,s.c). Morphine was administered 30min before orexin A intra-MPOA microinjection (four doses similar to experiment 1) or aCSF, then TF latency was measured.ResultsThe results indicated that microinjection of orexin A into the MPOA showed anti-nociceptive effect in a time-dependent manner. Dose response curve results also revealed that the maximum effective dose of orexin A injection into MPOA for pain inhibition is 1000pmol/0.5μl. Co-administration of systemic morphine and orexin into the MPOA has additive analgesia with different time course compared morphine or orexin alone.ConclusionIt can be concluded that MPOA OrexinA receptors play an important role in the modulation of pain in normal and morphine treated male rats.



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When machine vision meets histology: A comparative evaluation of model architecture for classification of histology sections

Publication date: January 2017
Source:Medical Image Analysis, Volume 35
Author(s): Cheng Zhong, Ju Han, Alexander Borowsky, Bahram Parvin, Yunfu Wang, Hang Chang
Classification of histology sections in large cohorts, in terms of distinct regions of microanatomy (e.g., stromal) and histopathology (e.g., tumor, necrosis), enables the quantification of tumor composition, and the construction of predictive models of genomics and clinical outcome. To tackle the large technical variations and biological heterogeneities, which are intrinsic in large cohorts, emerging systems utilize either prior knowledge from pathologists or unsupervised feature learning for invariant representation of the underlying properties in the data. However, to a large degree, the architecture for tissue histology classification remains unexplored and requires urgent systematical investigation. This paper is the first attempt to provide insights into three fundamental questions in tissue histology classification: I. Is unsupervised feature learning preferable to human engineered features? II. Does cellular saliency help? III. Does the sparse feature encoder contribute to recognition? We show that (a) in I, both Cellular Morphometric Feature and features from unsupervised feature learning lead to superior performance when compared to SIFT and [Color, Texture]; (b) in II, cellular saliency incorporation impairs the performance for systems built upon pixel-/patch-level features; and (c) in III, the effect of the sparse feature encoder is correlated with the robustness of features, and the performance can be consistently improved by the multi-stage extension of systems built upon both Cellular Morphmetric Feature and features from unsupervised feature learning. These insights are validated with two cohorts of Glioblastoma Multiforme (GBM) and Kidney Clear Cell Carcinoma (KIRC).

Graphical abstract

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