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1.
Trop Anim Health Prod ; 56(6): 204, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38995429

ABSTRACT

Mithun (Bos frontalis), a domestically raised herbivore, holds significant economic importance for the farming community of Northeast India. This study aimed to elucidate the genetic parameters governing Mithun body weight traits across different ages using data from the sole organized semi-intensive Mithun farm in India. Information was gathered from 110 Mithuns born over a period spanning from 2011 to 2022. Body weight taken at week 1 (W1), 1-month (M1), 3-months (M3), 6-months (M6), 9-months (M9), 12-months (M12), 30-months (M30) and 45-months (M45) were considered for the study. The genetic parameters estimation employed the BLUPF90 suite of programs, incorporating univariate Gibbs sampler animal model with fixed effects; season and period of birth, and sex of the animal. Variance and covariance components, including direct additive genetic effects, were estimated. Heritability estimates for the eight body weight traits ranged from 0.47 ± 0.0050 to 0.50 ± 0.0043, indicating varying genetic influence across growth stages. Results revealed that Mithun herd has a substantial genetic variability for growth traits and therefore there is ample scope to select for a better growth rate. Here, we conclude that Month 12 (M12) and Month 9 (M9) body weights exhibit higher heritability, indicating potential for genetic improvement through selective breeding.


Subject(s)
Body Weight , Animals , Male , Female , India , Models, Animal , Cattle/genetics , Cattle/growth & development , Cattle/physiology , Genetic Variation
2.
Food Chem X ; 22: 101349, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38623512

ABSTRACT

Edible coatings on fruits and vegetables preserve postharvest quality by reducing water loss and lowering respiration, and metabolic activities. The primary objectives of this study were to develop composite coating formulations using natural waxes (carnauba and shellac wax), eugenol nanoemulsion, and Aloe vera gel, and assess the potential impacts of the coating formulations on the postharvest quality and shelf-life of the Kaji lemon. The results show that eugenol nanoemulsion and Aloe vera gel enhanced the physico-chemical, antimicrobial and antioxidant properties of the developed coating. Notably, the fruits coated with optimized nanocomposite of wax with eugenol and aloe vera gel inclusion (SW + CW/EuNE-20/AVG-2) showed the lowest weight loss (16.56%), while the coatings of wax with only aloe vera gel (SW + CW/AVG-2) exhibited the highest firmness (48 N), in contrast to the control fruit, which had 27.33% weight loss and 9.6 N firmness after 28 days of storage, respectively.

3.
Curr Res Food Sci ; 8: 100720, 2024.
Article in English | MEDLINE | ID: mdl-38559379

ABSTRACT

In the evolving landscape of food packaging, lipid-based edible films and coatings are emerging as a sustainable and effective solution for enhancing food quality and prolonging shelf life. This critical review aims to offer a comprehensive overview of the functional properties, roles, and fabrication techniques associated with lipid-based materials in food packaging. It explores the unique advantages of lipids, including waxes, resins, and fatty acids, in providing effective water vapor, gas, and microbial barriers. When integrated with other biopolymers, such as proteins and polysaccharides, lipid-based composite films demonstrate superior thermal, mechanical, and barrier properties. The review also covers the application of these innovative coatings in preserving a wide range of fruits and vegetables, highlighting their role in reducing moisture loss, controlling respiration rates, and maintaining firmness. Furthermore, the safety aspects of lipid-based coatings are discussed to address consumer and regulatory concerns.

5.
Malays Orthop J ; 16(2): 95-101, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35992972

ABSTRACT

Introduction: Quadriceps angle (Q-angle) is the angle formed from the intersection of quadriceps femoris muscle and patellar tendon. Q-angle can be used to assess mechanical aspects of the patellofemoral discomfort and attracts considerable attention from clinicians. Anterior knee pain (AKP) is defined as mild pain localised around the peripatellar area exacerbated by physical activity such as climbing stairs, squatting, jumping, running, and/or sitting with the knee flexed for long periods. A higher Q-angle is one of the risk factors for AKP. In addition, several studies have found a relationship between anthropometric parameters, especially body mass index (BMI), to the occurrence of AKP. This study aims to determine the Q-angle and several anthropometric parameters between the population with AKP and without AKP in the adult population in Indonesia. Materials and methods: This cross-sectional, analytic experimental study was performed on female population divided into the comparison group consisted of 40 patients aged between 18-25 years with right side anterior knee pain (Kujala score <82) and the control group consisted of 40 patients aged between 18-25 years without anterior knee pain (Kujala score >82). Both groups had to be right-handed and had no history of knee fractures, knee surgery, congenital anomalies, or obesity. The Q-angle of the right knee was measured in all participants using a universal goniometer. Results: The mean Q-angle in the comparison group was 20.60±1.26°, and in the control group was 14.85±0.99°. All of these differences were statistically significant (p<0.001). There was no significant correlation between anthropometric parameters (body weight, body height, and body mass index) with AKP. Conclusion: The Q-angle can be used to predict the risk of AKP in the female population. The greater the Q-angle the higher the risk of AKP. Anthropometric measurements cannot predict the risk of AKP.

6.
Environ Res ; 203: 111841, 2022 01.
Article in English | MEDLINE | ID: mdl-34380049

ABSTRACT

TiO2, ZnO, and SnO2 metal oxides were synthesized by the sol-gel method and heterojunctions were fabricated by combining TiO2 with either ZnO or SnO2 in a 1:1 ratio using mechanochemical ball milling process. The ball milling process promotes phase transition of TiO2 from anatase to rutile and yields ternary heterojunction of the type TiO2(A)/TiO2(R)/ZnO and TiO2(A)/TiO2(R)/SnO2 (A-anatase and R-rutile). These ternary heterojunctions were characterized by various analytical techniques and its photocatalytic efficiency is evaluated using 4-Chloro Phenol as a model compound under UV and solar light. The enhanced catalytic activity of TiO2(A)/TiO2(R)/ZnO heterojunction is attributed to the formation of Ti3+-Vo defect states which leads to the efficient charge carrier separation. During the ball milling process severe crystal deformation takes place in TiO2 and ZnO lattices by creating crystal lattice distortion which leads to the formation of defects due to valency mismatch between Ti4+ and Zn2+. A mechanistic pathway is proposed for the enhanced photocatalytic activity of the ternary heterojunctions.


Subject(s)
Zinc Oxide , Light , Semiconductors , Titanium
7.
Dev Dyn ; 250(3): 450-464, 2021 03.
Article in English | MEDLINE | ID: mdl-32776603

ABSTRACT

BACKGROUND: Abnormal fetal movements are implicated in joint pathologies such as arthrogryposis and developmental dysplasia of the hip (DDH). Experimentally induced paralysis disrupts joint cavitation and morphogenesis leading to postnatal abnormalities. However, the developmental window(s) most sensitive to immobility-and therefore the best time for intervention-have never been identified. Here, we systematically vary the timing and duration of paralysis during early chick hip joint development. We then test whether external manipulation of immobilized limbs can mitigate the effects of immobility. RESULTS: Timing of paralysis affected the level of disruption to joints, with paralysis periods between embryonic days 4 and 7 most detrimental. Longer paralysis periods produced greater disruption in terms of failed cavitation and abnormal femoral and acetabular geometry. External manipulation of an immobilized limb led to more normal morphogenesis and cavitation compared to un-manipulated limbs. CONCLUSIONS: Temporary paralysis is detrimental to joint development, particularly during days 4 to 7. Developmental processes in the very early stages of joint development may be critical to DDH, arthrogryposis, and other joint pathologies. The developing limb has the potential to recover from periods of immobility, and external manipulation provides an innovative avenue for prevention and treatment of developmental joint pathologies.


Subject(s)
Acetabulum/embryology , Hip Joint/embryology , Morphogenesis , Paralysis , Animals , Chick Embryo
8.
Int J Biol Macromol ; 162: 685-692, 2020 Nov 01.
Article in English | MEDLINE | ID: mdl-32585271

ABSTRACT

The effect of 1-butyl-3-methylimidazolium chloride (BMIMCl) as a plasticizer on sol-gel phase transition, rheological, and physical properties of high amylose rice starch was studied. The inter-relationships of parameters were determined using principal component analysis. The sol-gel phase transition temperature and storage modulus of starch was varied significantly (p ≤ 0.05) in the presence of BMIMCl. The sol-gel phase transition temperature of native starch was varied between 53.99 and 39.7 °C, whereas, for starch with ionic liquid varied between 49.50 and 40.6 °C. The changes in storage modulus (G') during the sol-gel phase transition were suitable with first order kinetics. The temperature dependent rheology of starch during the sol-gel phase transition was efficiently (0.93 ≤ R2 ≤ 0.98) explained using the Arrhenius model. The thermal stability of the gel was improved in the presence of BMIMCl. The textural and electrical properties of the gel were significantly affected by the presence of BMIMCl. The inter-relationships between the parameters were developed and the initial temperature, resistance, and storage modulus showed a strong interrelation.


Subject(s)
Amylose/analysis , Gels/chemistry , Ionic Liquids/chemistry , Oryza/chemistry , Starch/chemistry , Kinetics , Phase Transition , Rheology , Temperature , Viscosity
9.
Br J Clin Pharmacol ; 85(10): 2428-2435, 2019 10.
Article in English | MEDLINE | ID: mdl-31323137

ABSTRACT

This study prospectively quantified wastage of cancer chemotherapeutic drugs in an oncology unit to find the associated cost in 3 months. Retrospective analysis of drug usage for 12 months was also conducted to determine the expected drug loss in 1 year. The effect of vial sharing was evaluated under the assumption of sharing. A significant drug wastage of 19.72% (95% confidence interval [CI], 14.52-24.93%) in 3 months and 17.14% (95% CI 14.69-19.59%) in 1 year occurred in our oncology unit. Number of vials purchased (r = 0.362, p < 0.01), weight (r = -0.146, P < .01) and body surface area (r = -0.26, P < .01) correlated with the drug wasted. Vial sharing assumption showed a 9% (95% CI, 2.5-15.5%) reduction in cost in 1 year.


Subject(s)
Antineoplastic Agents/administration & dosage , Neoplasms/drug therapy , Waste Products/statistics & numerical data , Adult , Aged , Antineoplastic Agents/economics , Body Surface Area , Drug Costs/statistics & numerical data , Female , Humans , India , Male , Middle Aged , Neoplasms/economics , Prospective Studies , Retrospective Studies , Tertiary Care Centers , Waste Products/economics
10.
Indian Dermatol Online J ; 10(4): 453-455, 2019.
Article in English | MEDLINE | ID: mdl-31334069

ABSTRACT

Tripe palms is an unusual cutaneous paraneoplastic syndrome characterized by a curious rugose thickening of the palms with an accentuation of the normal dermatoglyphic ridges and sulci. Tripe palms alone or in combination with acanthosis nigricans is strongly associated with internal malignancy, especially carcinomas of the gastrointestinal tract and lung. Any patient with tripe palms must have a complete cancer workup, as in many of the cases it often precedes the malignancy by many months. We report a rare case of tripe palms with acanthosis nigricans in a 50-year-old man with advanced pancreatic adenocarcinoma. Although relatively rare, an early diagnosis is very important to find out underlying malignancy and to improve the prognosis related to the neoplasia.

11.
Indian J Sex Transm Dis AIDS ; 40(1): 20-24, 2019.
Article in English | MEDLINE | ID: mdl-31143855

ABSTRACT

CONTEXT: After the introduction of highly active antiretroviral therapy (ART), the prevalence of hypogonadism among human immunodeficiency virus (HIV)-infected males is decreasing. AIMS: The aim of this study was (i) to estimate the prevalence of hypogonadism among HIV-infected males and (ii) to determine the risk factors for hypogonadism. SETTINGS AND DESIGN: This was a cross-sectional study undertaken at ART center of a medical Institute. SUBJECTS AND METHODS: The study recruited HIV-infected males aged 18-65 years receiving ART. Patients with any debilitating chronic illness, diabetes mellitus, chronic smokers or alcoholic, currently on opioids, or methadone were excluded from the study. Androgen Deficiency in Aging Male (ADAM) questionnaire was used to screen patients for the possible presence of hypogonadism. For those screened positive on ADAM questionnaire underwent biochemical evaluation for serum total testosterone, luteinizing hormone (LH), and CD4 count. STATISTICAL ANALYSIS USED: The Chi-square test was used to compare different parameters. Pearson's correlation coefficient was used to assess any relationship between CD4 count, LH, and testosterone. P < 0.05 was considered statistically significant. RESULTS: In the study, 426 were initially screened and 120 patients who had probable hypogonadism were further evaluated. The mean age of the patients was 41.61 years. The mean body mass index (BMI) of the patients was 22.47 kg/m2. The mean duration of ART was 6.13 years and the mean CD4 count was 442.63 cells/mm3. Hypogonadism was seen in 20 (23.3%) and majority (85.7%) had secondary hypogonadism. There was significant association between hypogonadism and CD4 count, but no association was found with BMI and duration of ART. CONCLUSIONS: Hypogonadism is seen in 23.3% of HIV-infected males. Majority (85.7%) had secondary hypogonadism. There was significant association of hypogonadism with lower CD4 count.

12.
Vet World ; 11(3): 348-354, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29657428

ABSTRACT

AIM: The present study was conducted to detect and identify the virulence genes in Pasteurella multocida isolates of porcine origin from Assam. MATERIALS AND METHODS: A total of 21 porcine P. multocida isolates were subjected to capsular typing and detection of virulence-associated genes (pfhA, tbpA, hgbB, toxA, oma87, ompH, and nanB) using various polymerase chain reaction (PCR) methods reported elsewhere. Further, pathogenicity of the porcine isolates of P. multocida was studied in mice. For each strain of P. multocida selected for pathogenicity trial, the group of mice was injected intraperitoneally (i/p) with 0.1 ml of the inoculum prepared from respective field isolates, containing 109 organisms per ml. RESULTS: Capsular typing of the isolates by multiplex PCR showed two capsular types, type A (66.66%) and type D (33.33%). All the isolates were positive for outer membrane protein genes, oma87 and ompH genes. Iron acquisition genes, tbpA and hgbB, were detected in 14.28% and 19.04% of the isolates. The dermonecrotoxin encoding gene, toxA, was present in 23.80% of the isolates. Filamentous hemagglutinin encoding gene, pfhA, was detected in 28.57%. The virulence gene distribution pattern of the isolates indicates the important role of the genes in disease pathogenesis. CONCLUSION: From the present study, it can be concluded that toxA gene is an important marker gene for defining the pathogenic potential of P. multocida strains in swine.

14.
Micron ; 82: 41-51, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26774744

ABSTRACT

Scanning Electron Microscopy (SEM) and Light Microscopy (LM) of the oral apparatus of Polypedates teraiensis and Hylarana leptoglossa tadpoles revealed a number of morphological and microstructural alterations in the labial tooth rows, jaw sheaths and marginal papillae on exposure to acidic and alkaline pH. These morphological and microstructural alterations observed in the oral apparatus of the tadpole are discussed in the light of available literature. The significance of the study with reference to adverse effects of acidic as well as alkaline pH on oral apparatus of the tadpole is also discussed.


Subject(s)
Anura/anatomy & histology , Larva/anatomy & histology , Animals , Cell Membrane Structures/ultrastructure , Hydrogen-Ion Concentration , Larva/physiology , Microscopy, Electron, Scanning/methods , Microscopy, Polarization , Mouth/anatomy & histology , Mouth/physiology , Mouth/ultrastructure
15.
Neuroscience ; 307: 128-37, 2015 Oct 29.
Article in English | MEDLINE | ID: mdl-26314636

ABSTRACT

ß-Site APP-cleaving enzyme 1 (BACE1) initiates the generation of amyloid-ß (Aß), thus representing a prime therapeutic target for Alzheimer's disease (AD). Previous work including ours has used BACE1 haploinsufficiency (BACE1(+/-); i.e., 50% reduction) as a therapeutic relevant model to evaluate the efficacy of partial ß-secretase inhibition. However, it is unclear whether the extent of Aß reductions in amyloid precursor protein (APP) transgenic mice with BACE1(+/-) gene ablation may vary with sex or disease progression. Here, we compared the impacts of BACE1 haploinsufficiency on Aß concentrations and APP processing in 5XFAD Alzheimer mice (1) between males and females and (2) between different stages with moderate and robust Aß accumulation. First, male and female 5XFAD mice at 6-7 months of age showed equivalent levels of Aß, BACE1, full-length APP and its metabolites. BACE1 haploinsufficiency significantly lowered soluble Aß oligomers, total Aß42 levels and plaque burden in 5XFAD mouse brains irrespective of sex. Furthermore, there was no sex difference in reductions of ß-cleavage products of APP (C99 and sAPPß) found in BACE1(+/-)·5XFAD mice relative to BACE1(+/+)·5XFAD controls. Meanwhile, APP and sAPPα levels in BACE1(+/-)·5XFAD mice were higher than those of 5XFAD controls regardless of sex. Based on these observations, we next combined male and female data to examine the effects of BACE1 haploinsufficiency in 5XFAD mice at 12-14 months of age, as compared with those in 6-7-month-old 5XFAD mice. Oligomeric Aß and C99 levels were dramatically elevated in older 5XFAD mice. Although the ß-metabolites of APP were significantly reduced by BACE1 haploinsufficiency in both age groups, high levels of these toxic amyloidogenic fragments remained in 12-14-month-old BACE1(+/-)·5XFAD mice. The present findings are consistent with our previous behavioral data showing that BACE1 haploinsufficiency rescues memory deficits in 5XFAD mice irrespective of sex but only in the younger age group.


Subject(s)
Amyloid Precursor Protein Secretases/deficiency , Amyloid beta-Peptides/metabolism , Amyloid beta-Protein Precursor/metabolism , Aspartic Acid Endopeptidases/deficiency , Gene Expression Regulation/genetics , Presenilin-1/metabolism , Sex Characteristics , Amyloid Precursor Protein Secretases/genetics , Amyloid beta-Peptides/genetics , Amyloid beta-Protein Precursor/genetics , Analysis of Variance , Animals , Aspartic Acid Endopeptidases/genetics , Disease Models, Animal , Disease Progression , Enzyme-Linked Immunosorbent Assay , Female , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Mutation/genetics , Presenilin-1/genetics
16.
Transl Psychiatry ; 5: e562, 2015 May 05.
Article in English | MEDLINE | ID: mdl-25942043

ABSTRACT

Accumulating evidence shows that brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase B (TrkB) significantly decrease early in Alzheimer's disease (AD). However, it remains unclear whether BDNF/TrkB reductions may be mechanistically involved in the pathogenesis of AD. To address this question, we generated 5XFAD transgenic mice with heterozygous TrkB knockout (TrkB(+/-)·5XFAD), and tested the effects of TrkB reduction on AD-like features in this mouse model during an incipient stage that shows only modest amyloid-ß (Aß) pathology and retains normal mnemonic function. TrkB(+/-) reduction exacerbated memory declines in 5XFAD mice at 4-5 months of age as assessed by the hippocampus-dependent spontaneous alternation Y-maze task, while the memory performance was not affected in TrkB(+/-) mice. Meanwhile, TrkB(+/-)·5XFAD mice were normal in nest building, a widely used measure for social behavior, suggesting the memory-specific aggravation of AD-associated behavioral impairments. We found no difference between TrkB(+/-)·5XFAD and 5XFAD control mice in cerebral plaque loads, Aß concentrations including total Aß42 and soluble oligomers and ß-amyloidogenic processing of amyloid precursor protein. Interestingly, reductions in hippocampal expression of AMPA/NMDA glutamate receptor subunits as well as impaired signaling pathways downstream to TrkB such as CREB (cAMP response element-binding protein) and Akt/GSK-3ß (glycogen synthase kinase-3ß) were observed in TrkB(+/-)·5XFAD mice but not in 5XFAD mice. Among these signaling aberrations, only Akt/GSK-3ß dysfunction occurred in TrkB(+/-) mice, while others were synergistic consequences between TrkB reduction and subthreshold levels of Aß in TrkB(+/-)·5XFAD mice. Collectively, our results indicate that reduced TrkB does not affect ß-amyloidosis but exacerbates the manifestation of hippocampal mnemonic and signaling dysfunctions in early AD.


Subject(s)
Alzheimer Disease/genetics , Amyloid beta-Peptides/metabolism , Brain/metabolism , Membrane Glycoproteins/genetics , Memory Disorders/genetics , Peptide Fragments/metabolism , Plaque, Amyloid/genetics , Protein-Tyrosine Kinases/genetics , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Animals , Brain/pathology , Brain-Derived Neurotrophic Factor/metabolism , Cyclic AMP Response Element-Binding Protein/metabolism , Disease Models, Animal , Glycogen Synthase Kinase 3/metabolism , Glycogen Synthase Kinase 3 beta , Heterozygote , Memory , Memory Disorders/metabolism , Memory Disorders/pathology , Mice , Mice, Knockout , Plaque, Amyloid/pathology , Proto-Oncogene Proteins c-akt , Receptors, AMPA/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Signal Transduction
17.
Vet World ; 8(12): 1375-8, 2015 Dec.
Article in English | MEDLINE | ID: mdl-27047046

ABSTRACT

AIM: The aim of the present study was to generate baseline data on the normal values of the thyroidhormone (TH) activity as well as their correlation with age and season. MATERIALS AND METHODS: Blood samples (10 ml) were collected from jugular vein of 30 female mithun's of three different age groups viz. Calves (6 months to 1 year), heifer (1-3 years) and adult (above 3 years) during the three season's viz. Monsoon, winter and spring of a year. The serum was analyzed for thyroid stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) activity. RESULT: The result showed a significantly (p<0.05) a higher T3 level in heifers followed by adults and calves and higher T4 level in adults followed by heifers and calves in all the seasons. The TSH level was higher in heifers in all the seasons. The winter season recorded higher level of T3, T4, and TSH as compared to the other seasons of a year. CONCLUSION: The TSH and T3 level were the highest for aheifer, whereas T4 level was the highest for adults inall the season. Furthermore, the higher level of TH was observed in winter season. The increased level of the TH during the winter season signifies their calorigenic effect. Similarly in heifers, the increased T3 concentrations show its importance in reproductive physiology and its association with ovarian activity. This indicates that age and season have aprofound effect on TH activity of Mizoram strain female mithun.

18.
Indian J Surg Oncol ; 6(3): 288-91, 2015 Sep.
Article in English | MEDLINE | ID: mdl-27217682

ABSTRACT

Askin's tumor is a primitive neuroectodermal tumor (PNET) developing from the soft tissues of the chest wall and mainly occur in children and adolescents. The management approach is complex and requires a multidisciplinary team. We report a case of locally advanced Askin's tumour in a child because of its rarity and also to highlight the importance of keeping the possibility of PNET tumours in mind while dealing with cases of chest wall tumour in children.

19.
Spectrochim Acta A Mol Biomol Spectrosc ; 135: 120-36, 2015 Jan 25.
Article in English | MEDLINE | ID: mdl-25062058

ABSTRACT

Aromatic epoxides are causative factors for mutagenic and carcinogenic activity of polycyclic arenes. The 1,2- or 2,3-epoxy compounds are widely used to a considerable extent in the textile, plastics, pharmaceutical, cosmetics, detergent and photochemical industries. The FTIR and FT-Raman spectra of (1,2-epoxyethyl)benzene and (1,2-epoxy-2-phenyl)propane are recorded in the regions 4000-400 cm(-1) and 4000-100 cm(-1), respectively. The observed fundamentals are assigned to different normal modes of vibration. The structure of the compound has been optimised with B3LYP method using 6-311++G(**) and cc-pVTZ basis sets. The IR and Raman intensities are determined. The total electron density and molecular electrostatic potential surfaces of the molecule are constructed by using B3LYP/6-311++G(d,p) method to display electrostatic potential (electron+nuclei) distribution. The electronic properties HOMO and LUMO energies were measured. Natural bond orbital analysis of the compounds has been performed to indicate the presence of intramolecular charge transfer. The (1)H and (13)C NMR chemical shifts of the molecules have been analysed.


Subject(s)
Benzene Derivatives/chemistry , Benzene/chemistry , Carbon-13 Magnetic Resonance Spectroscopy , Epoxy Compounds/chemistry , Models, Molecular , Propane/analogs & derivatives , Propane/chemistry , Proton Magnetic Resonance Spectroscopy , Quantum Theory , Spectroscopy, Fourier Transform Infrared , Electrons , Molecular Conformation , Spectrum Analysis, Raman , Static Electricity , Structure-Activity Relationship , Thermodynamics , Vibration
20.
Br J Pharmacol ; 172(2): 704-19, 2015 Jan.
Article in English | MEDLINE | ID: mdl-24990314

ABSTRACT

BACKGROUND AND PURPOSE: Opioid receptor function is modulated by post-activation events such as receptor endocytosis, recycling and/or degradation. While it is generally understood that the peptide ligand gets co-endocytosed with the receptor, relatively few studies have investigated the role of the endocytosed peptide and peptide processing enzymes in regulating receptor function. In this study, we focused on endothelin-converting enzyme 2 (ECE2), a member of the neprilysin family of metallopeptidases that exhibits an acidic pH optimum, localizes to an intracellular compartment and selectively processes neuropeptides including opioid peptides in vitro, and examined its role in modulating µ receptor recycling and resensitization. EXPERIMENTAL APPROACH: The effect of ECE2 inhibition on hydrolysis of the endocytosed peptide was examined using thin-layer chromatography and on µ opioid receptor trafficking using either elisa or microscopy. The effect of ECE2 inhibition on receptor signalling was measured using a cAMP assay and, in vivo, on antinociception induced by intrathecally administered opioids by the tail-flick assay. KEY RESULTS: The highly selective ECE2 inhibitor, S136492, significantly impaired µ receptor recycling and signalling by only those ligands that are ECE2 substrates and this was seen both in heterologous cells and in cells endogenously co-expressing µ receptors with ECE2. We also found that ECE2 inhibition attenuated antinociception mediated only by opioid peptides that are ECE2 substrates. CONCLUSIONS AND IMPLICATIONS: These results suggest that ECE2, by selectively processing endogenous opioid peptides in the endocytic compartment, plays a role in modulating opioid receptor activity. LINKED ARTICLES: This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.


Subject(s)
Aspartic Acid Endopeptidases/metabolism , Metalloendopeptidases/metabolism , Opioid Peptides/pharmacology , Receptors, Opioid, mu/metabolism , Animals , Aspartic Acid Endopeptidases/antagonists & inhibitors , CHO Cells , Cricetulus , Cyclic AMP/metabolism , Endocytosis , Endothelin-Converting Enzymes , Hydrogen-Ion Concentration , Hydrolysis , Male , Metalloendopeptidases/antagonists & inhibitors , Mice, Inbred C57BL , Protein Transport , Receptors, Opioid, mu/agonists , Signal Transduction
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