ABSTRACT
Este estudo teve como objetivo avaliar as relações de valina:lisina digestíveis em dietas com teor reduzido de proteína bruta (PB) e os efeitos dessa redução sobre desempenho e rendimento de carcaça em frangos de corte. Foram utilizados 1200 pintos machos seguindo modelo inteiramente ao acaso, com seis tratamentos de seis repetições (exceto controle, com 10 repetições), compostos por 30 aves cada. O tratamento controle (T1) foi formulado conforme os níveis de proteína bruta e aminoácidos (AAs) recomendados por Rostagno et al . (2011), e os demais tratamentos (T2 a T6) tiveram seus níveis de PB reduzidos (4% em relação ao controle) e variaram em função da relação valina:lisina digestíveis, com cinco níveis equidistantes em intervalos de 0,07:1, variando de 0,63:1 e 0,91:1 (dietas até 21 dias) e de 0,64:1 e 0,92:1 (dietas após 21 dias). As seguintes características de desempenho foram avaliadas: ganho de peso, consumo de ração, conversão alimentar, viabilidade criatória e índice de eficiência produtiva. Aos 46 dias de idade, seis animais por repetição foram abatidos para determinação de rendimento de carcaça e de cortes comerciais. As diferentes relações valina:lisina digestíveis não influenciaram o desempenho dos animais (P>0,05) para nenhuma característica avaliada. A redução proteica piorou a conversão alimentar dos animais (P≤0,05) até os 21 dias. Os resultados sugerem que os níveis de valina utilizados não afetam o desempenho dos animais, apenas o rendimento de peito e que, portanto, a redução proteica não é recomendada durante as três primeiras semanas de criação.
This study aimed to evaluate valine:lysine ratios in diets with reduced content of crude protein and the effects of this reduction on the performance of broiler chickens. 1200 male chicks were used following a complete randomized design with six replicates of six treatments (except control, with 10 replicates), each one with 30 chicks. The control treatment (T1) was formulated following levels of crude protein (CP) and the amino acids (AAs) recommended by Rostagno et al. (2011), and the other treatments (T2 to T6) had reduced levels of CP (4 % compared to control) and varied in proportion valine:lysine, with 5 levels at equidistant intervals 0.07:1 ranging from 0.63:1 to 0.91:1 (up to 21 days) and from 0.64:1 to 0.92:1 (after 21 days). The performance characteristics measured were: weight gain, feed intake, feed conversion, viability and productive efficiency index. At 46 days six animals per replicate were slaughtered for evaluation of carcass and commercial cuts. The different valine:lysine ratios did not affect animal performance (P>0.05). Reducing protein impaired feed conversion (P≤.05) up to 21 days. The results suggest that levels of valine used did not affect the broilers' performance, however, breast meat yield and reduced protein are not recommended during the first three weeks.
Subject(s)
Animals , Male , Amino Acids/administration & dosage , Diet/veterinary , Dietary Proteins/administration & dosage , Dietary Proteins/analysis , Valine/administration & dosage , Enkephalin, Methionine/administration & dosage , Lysine/administration & dosage , Threonine/administration & dosage , Tryptophan/administration & dosageABSTRACT
<p><b>OBJECTIVE</b>To observe the analgesic effect of electroacupuncture (EA) on collagen-induced arthritis (CIA) rats and its regulating effect on inflammation reaction and the endogenous opioid system of synovial tissues. Methods A total of 30 healthy male Wistar rats were randomly divided into a control group, a model group and an EA group, 10 rats in each one. The chronic pain model of CIA rats was made by cattle type-II collagen in the model group and EA group. Rats in the EA group were treated with EA at "Zusanli" (ST 36) and "Kunlun" (BL 60) for 30 min from 16th day after model establishment, once a day for consecutive 10 days. Rats in the control group did not receive any treatment. Rats in the model group were treated with fixation as the EA group. Threshold of pain, arthritis index, paw swelling were measured before model establishment and 16 d, 20 d, 23 d and 25 d after model establishment. The levels of beta-endorphin (β-END), met-enkephalin (met-ENK), dynorphin A (Dyn A) were measured by radioimmunoassay; the mRNA expressions of mu opioid receptor (MOR), kappa opioid receptor (KOR) and delta opioid receptor (DOR) in synovial tissues of CIA rats were detected by I quantitative polymerase chain reaction (qPCR).</p><p><b>RESULTS</b>Compared with the control group, threshold of pain was reduced (all P<0. 01), arthritis index was increased (all P<0. 01) and paw swelling was increased (all P<0. 01) in the model group on the 16th day, 20th day, 23rd day, 25th day after model establishment. Compared with the model group, the threshold of pain was increased in the EA group (all P<0. 01), arthritis index and paw swelling were reduced (all P<0. 01) on the 23rd day and 25th day after model establishment. Compared with the control group, the level of Dyn A in synovial tissues of CIA rats was increased in the model group (P<0. 01); the mRNA expressions of MOR, KOR and DOR were down-regulated lower than 0. 5 fold of normal level. Compared with the model group, the level of β-END in synovial tissues of the knee joint was increased in the EA group (P<0. 05), and the mRNA expressions of MOR, KOR and DOR in synovial tissues of CIA rats were up-regulated more than 2 folds of normal level.</p><p><b>CONCLUSION</b>The intervention of EA on chronic pain of CIA rats is superior, which is likely to be related with effects of EA on anti-inflammation and up-regulation of synovial tissue β-END and MOR, KOR, DOR.</p>
Subject(s)
Animals , Cattle , Humans , Male , Rats , Acupuncture Analgesia , Acupuncture Points , Analgesics, Opioid , Allergy and Immunology , Arthritis, Rheumatoid , Allergy and Immunology , Therapeutics , Chronic Pain , Allergy and Immunology , Therapeutics , Dynorphins , Genetics , Allergy and Immunology , Electroacupuncture , Enkephalin, Methionine , Genetics , Allergy and Immunology , Rats, Wistar , Receptors, Opioid, mu , Genetics , Allergy and Immunology , Synovial Fluid , Allergy and Immunology , beta-Endorphin , Genetics , Allergy and ImmunologyABSTRACT
Introduction: Tuberculosis is a common opportunistic infection in renal transplant patients. Objective: To obtain a clinical and laboratory description of transplant patients diagnosed with tuberculosis and their response to treatment during a period ranging from 2005 to 2013 at the Pablo Tobón Uribe Hospital. Methods: Retrospective and descriptive study. Results: In 641 renal transplants, tuberculosis was confirmed in 12 cases. Of these, 25% had a history of acute rejection, and 50% had creatinine levels greater than 1.5 mg/dl prior to infection. The disease typically presented as pulmonary (50%) and disseminated (33.3%). The first phase of treatment consisted of 3 months of HZRE (isoniazid, pyrazinamide, rifampicin and ethambutol) in 75% of the cases and HZME (isoniazid, pyrazinamide, moxifloxacin and ethambutol) in 25% of the cases. During the second phase of the treatment, 75% of the cases received isoniazid and rifampicin, and 25% of the cases received isoniazid and ethambutol. The length of treatment varied between 6 and 18 months. In 41.7% of patients, hepatotoxicity was associated with the beginning of anti-tuberculosis therapy. During a year-long follow-up, renal function remained stable, and the mortality rate was 16.7%. Conclusion: Tuberculosis in the renal transplant population studied caused diverse nonspecific symptoms. Pulmonary and disseminated tuberculosis were the most frequent forms and required prolonged treatment. Antituberculosis medications had a high toxicity and mortality. This infection must be considered when patients present with a febrile syndrome of unknown origin, especially during the first year after renal transplant. .
Introdução: A tuberculose é uma infecção oportunista comum em pacientes transplantados renais. Objetivo: Oferecer uma descrição clínica e laboratorial de pacientes transplantados com diagnóstico de tuberculose e sua resposta ao tratamento durante o período entre 2005 e 2013 no Hospital Pablo Tobón Uribe. Métodos: Estudo retrospectivo descritivo. Resultados: Em 641 transplantes renais, a tuberculose foi confirmada em 12 pacientes. Destes, 25% tinham histórico de rejeição aguda e 50% apresentaram níveis de creatinina superiores a 1,5 mg/dl antes da infecção. A patologia geralmente se apresentava como pulmonar (50%) e disseminada (33,3%). A primeira fase do tratamento consistiu de três meses de HZRE (isoniazida, pirazinamida, rifampicina e etambutol) em 75% dos casos e HZME (isoniazida, pirazinamida, moxifloxacina e etambutol) em 25% dos pacientes. Durante a segunda fase do tratamento, 75% dos pacientes receberam isoniazida e rifampicina e 25% isoniazida e etambutol. A duração do tratamento variou entre seis e 18 meses. Em 41,7% dos pacientes, hepatotoxicidade foi associada ao início do tratamento da tuberculose. Durante o seguimento de um ano a função renal manteve-se estável e a taxa de mortalidade foi de 16,7%. Conclusão: A tuberculose foi responsável por diversos sintomas inespecíficos na população de transplantados renais estudada. Tuberculose pulmonar e disseminada foram as formas mais frequentes de acometimento e necessitaram de tratamento prolongado. Medicamentos contra a tuberculose apresentaram alta toxicidade e mortalidade. Esta infecção deve ser considerada quando o paciente apresenta síndrome febril de origem desconhecida, especialmente durante o primeiro ano após o transplante renal. .
Subject(s)
Animals , Female , Male , Mice , Locus Coeruleus/drug effects , Narcotics/pharmacology , Neural Inhibition/drug effects , Neurons/drug effects , Potassium Channels/metabolism , Barium/pharmacology , Calcium/metabolism , Enkephalin, Methionine/pharmacology , G Protein-Coupled Inwardly-Rectifying Potassium Channels , GTP-Binding Proteins/metabolism , Heterozygote , Homozygote , Ion Channel Gating/drug effects , Ion Channel Gating/physiology , Locus Coeruleus/cytology , Locus Coeruleus/physiology , Mice, Knockout , Membrane Potentials/drug effects , Membrane Potentials/physiology , Neural Inhibition/physiology , Neurons/physiology , Patch-Clamp Techniques , Protein Subunits , Potassium Channel Blockers/pharmacology , Potassium Channels, Inwardly Rectifying/antagonists & inhibitors , Potassium Channels, Inwardly Rectifying/deficiency , Potassium Channels, Inwardly Rectifying/genetics , Potassium Channels, Inwardly Rectifying/metabolism , Potassium Channels/deficiency , Potassium Channels/geneticsABSTRACT
OBJECTIVES: To predict the structure of protein, which dictates the function it performs, a newly designed algorithm is developed which blends the concept of self-organization and the genetic algorithm. METHODS: Among many other approaches, genetic algorithm is found to be a promising cooperative computational method to solve protein structure prediction in a reasonable time. To automate the right choice of parameter values the influence of self-organization is adopted to design a new genetic operator to optimize the process of prediction. Torsion angles, the local structural parameters which define the backbone of protein are considered to encode the chromosome that enhances the quality of the confirmation. Newly designed self-configured genetic operators are used to develop self-organizing genetic algorithm to facilitate the accurate structure prediction. RESULTS: Peptides are used to gauge the validity of the proposed algorithm. As a result, the structure predicted shows clear improvements in the root mean square deviation on overlapping the native indicates the overall performance of the algorithm. In addition, the Ramachandran plot results implies that the conformations of phi-psi angles in the predicted structure are better as compared to native and also free from steric hindrances. CONCLUSIONS: The proposed algorithm is promising which contributes to the prediction of a native-like structure by eliminating the time constraint and effort demand. In addition, the energy of the predicted structure is minimized to a greater extent, which proves the stability of protein.
Subject(s)
Enkephalin, Methionine , Islet Amyloid Polypeptide , Operator Regions, Genetic , PeptidesABSTRACT
BACKGROUND: The aim of this study is to investigate the cardio-metabolic parameters and surrogate markers of insulin resistance in a discordant group of type 2 diabetes (T2DM) subjects who satisfy the Adults Treatment Panel (ATP) III criteria, but not the International Diabetes Federation (IDF) criteria, for metabolic syndrome (MetS). METHODS: We assessed the prevalence of MetS in T2DM subjects (n=167) who were selected from subjects registered at the diabetes center of Dong-A University Medical Center. We used the ATP III criteria and the IDF criteria for the diagnosis of MetS and sorted the subjects into 2 MetS groups: one group diagnosed per ATP III criteria (MetSa) and one diagnosed per IDF criteria (MetSi). We then compared the clinical characteristics, metabolic parameters (homeostasis model assessment of insulin resistance, aspartate aminotransferase, alanine aminotransferase, and uric acid values) and co-morbidities (prevalence of microalbuminuria, fatty liver, and cardiovascular disease) between the MetSa, MetSi, and discordant MetS groups. RESULTS: The prevalence of MetS in the MetSa group (73.6%) was higher than in the MetSi group (62.2%). The MetS prevalence in the discordant group was 11.4%. The discordant group showed no significant differences in clinical characteristics (except waist circumference and body mass index), metabolic parameters, or prevalence of co-morbidities, as compared with subjects with MetS by both criteria. CONCLUSION: In this study, cardio-metabolic features of the subjects diagnosed with MetS using ATP III criteria, but not IDF criteria, are not significantly different from those of subjects diagnosed with MetS using both criteria.
Subject(s)
Adult , Humans , Academic Medical Centers , Adenosine Triphosphate , Alanine Transaminase , Aspartate Aminotransferases , Biomarkers , Diabetes Mellitus , Enkephalin, Methionine , Fatty Liver , Insulin Resistance , Prevalence , Uric Acid , Waist CircumferenceABSTRACT
The present study investigated the effects of intrathecal (i.t.) application of bovine adrenal medulla 22 (BAM22), an endogenous opioid peptide potently activating opioid receptors and sensory neuron-specific receptor (SNSR), on a model of complete Freund's adjuvant (CFA)-induced inflammatory pain. Unilateral, but not bilateral, inflammatory pain was induced by intraplantar (i.pl.) injection of CFA in one side, as indicated by the shortened paw withdrawal latency and the increased edema of paw. Paw withdrawal latency test, paw edema determination and immunohistochemistry were used in CFA-induced inflammatory pain model after i.t. administration of BAM22 or saline. It was found that administration of BAM22 dose-dependently attenuated CFA-induced hyperalgesia and edema, and resumed antinociceptive effects against thermal stimulation in behavioral test. In 10 nmol BAM22 group, paw withdrawal latency was resumed to 83.2% of normal, and edema increased only by 60% of normal at 48 h. The potency of BAM22 was 33.5% of maximal possible effect (MPE) at 24 h, and the antinociception persisted for at least 1 h. Furthermore, i.t. treatment of 10 nmol BAM22 evidently decreased the expressions of CFA-evoked neuronal nitric oxide synthase (nNOS)-positive cells and calcitonin gene-related peptide (CGRP)-immunoreactivity positive nerve fibers by 25.6% (P<0.01) and 25.2% (P<0.001) compared with saline group, respectively, at L3-L5 segments of the spinal cord. Small and medium CGRP-positive cells were 57.4% and 35.2% in dorsal root ganglion (DRG) in 10 nmol BAM22 group, respectively, which were remarkably lower than those in saline group (P<0.001). The present study suggests that BAM22 relieves CFA-induced thermal hyperalgesia in the early phase and resumes antinociceptive effects through down-regulation of nNOS and CGRP expressions in DRG and spinal cord, which is possibly mediated via SNSR.
Subject(s)
Animals , Male , Rats , Calcitonin Gene-Related Peptide , Metabolism , Enkephalin, Methionine , Pharmacology , Freund's Adjuvant , Hyperalgesia , Inflammation , Nitric Oxide Synthase Type I , Metabolism , Pain , Pain Measurement , Protein Precursors , Pharmacology , Rats, Sprague-Dawley , Receptors, G-Protein-Coupled , PhysiologyABSTRACT
To address the role of the opioid system in the pathogenesis of hepatic encephalopathy [HE] we measured plasma met- enkephalin, beta -endorphin and leu- enkephalin in patients with different grades of HE compared to control subjects and patients with cirrhosis. Plasma met- enkephalin levels were significantly higher in patients with cirrhosis and all grades of HE than controls. Plasma beta levels were similar in the 3 groups. Plasma leu- enkephalin levels were significantly higher -endorphin in HE grades II, III and IV than in controls, patients with cirrhosis and HE grade I patients. Our results support data on the involvement of met- enkephalin and leu- enkephalin in the pathogenesis of HE and provide a rationale for the use of opioid receptor antagonists in the treatment of HE
Subject(s)
Female , Humans , Male , Hepatic Encephalopathy/physiopathology , Enkephalin, Methionine/blood , Enkephalin, Leucine , Opioid Peptides/blood , beta-Endorphin/blood , Liver Function TestsABSTRACT
<p><b>BACKGROUND</b>Preconditioning with repeated electroacupuncture (EA) could mimic ischemic preconditioning to induce cerebral ischemic tolerance in rats. The present study was designed to investigate whether mu (micro)-, delta (delta)- or kappa (kappa)-opioid receptors are involved in the neuroprotection induced by repeated EA preconditioning.</p><p><b>METHODS</b>The rats were pretreated with naltrindole (NTI), nor-binaltorphimine (nor-BNI) or D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), which is a highly selective delta-, kappa- or micro-opioid receptor antagonist respectively, before each EA preconditioning (30 minutes per day, 5 days). Twenty-four hours after the last EA treatment, the middle cerebral artery occlusion (MCAO) was induced for 120 minutes. The brain infarct volume was determined with 2, 3, 5-triphenyltetrazolium chloride staining at 24 hours after MCAO and compared with that in rats which only received EA preconditioning. In another experiment, the met-enkephalin-like immunoreactivity in rat brain was investigated by immunohistochemistry in both EA preconditioning and control rats.</p><p><b>RESULTS</b>The EA preconditioning reduced brain infarct volume compared with the control rats (P = 0.000). Administration of both NTI and CTOP attenuated the brain infarct volume reduction induced by EA preconditioning, presenting with larger infarct volume than that in the EA preconditioning rats (P < 0.001). But nor-BNI administration did not block the infarct volume reduction induced by EA preconditioning, presenting with smaller infarct volume than the control group rats (P = 0.000). The number of met-enkephalin-like immunoreactivity positive neurons in the EA preconditioning rats was more than that of the control rats (P = 0.000).</p><p><b>CONCLUSION</b>Repeated EA preconditioning stimulates the release of enkephalins, which may bind delta- and micro-opioid receptors to induce the tolerance against focal cerebral ischemia.</p>
Subject(s)
Animals , Male , Rats , Brain Ischemia , Electroacupuncture , Enkephalin, Methionine , Immunohistochemistry , Ischemic Preconditioning , Naltrexone , Pharmacology , Rats, Sprague-Dawley , Receptors, Opioid, delta , Physiology , Receptors, Opioid, mu , Physiology , Somatostatin , PharmacologyABSTRACT
A complete normal coordinate analysis of morphine using Wilson's GF matrix method and Urey Bradley force field has been carried out to understand the dynamical behaviour of morphine in relation to Leu5- and Met5-enkephalins. In addition, charge distribution on different atoms of morphine, along with that of Leu5- and Met5-enkephalins using CNDO/2 method is also reported. The similarity in charge distribution on some of the sites of these molecules is indicative of the possible interactions at the same receptor site. It is surmised that the recognition and interaction of active sites with the receptor must be dynamical in nature and for this the modes involving the active sites should play an important role. It is found that the binding to receptors is not static, but a dynamic process.
Subject(s)
Analgesics, Opioid/chemistry , Binding Sites , Enkephalin, Leucine/chemistry , Enkephalin, Methionine/chemistry , Molecular Structure , Morphine/chemistry , Receptors, Opioid/metabolism , Spectroscopy, Fourier Transform Infrared , Spectrum Analysis, RamanABSTRACT
BACKGROUND: Adrenal medullary transplants into the subarachnoid space have been demonstrated to reduce pain sensitivity. This analgesia most likely results from the release of neuroactive substances, particularly catecholamines and opioid peptides from the transplanted cells into spinal cord. METHODS: Isolated bovine chromaffin cells were encapsulated with alginate and poly-L-lysine prior to implantation into rat's subarachnoid space to protect them from host immune system. And then catecholamines from encapsulated chromaffin cells were measured quantitatively in vitro by High Performance Liquid Chromatograph. The animals were randomized into 2 groups, one of which received microencapsulated chromaffin cells and the other empty capsules. The effects of such implants were evaluated on the pain behavior resulting from a chronic constriction injury of the rat sciatic nerve for 30 days. RESULTS: Catecholamine concentration in cerebrospinal fluid (CSF) was analyzed. Data (mean SD) are considered significant at P <0.05 (ANOVA for repeated measure and Dunnett's test). Continuous release of catecholamine and met-enkephalin with responsiveness to nicotine stimulation was measured from encapsulated cells in vitro. A significant reduction of allodynic response to acetone evaporation was observed in the animals implanted with cell loaded capsules compared to control animals with empty capsules. Catecholamine concentration in CSF was higher in the cell loaded capsule group. There were no complications related to implantation. CONCLUSION: We found that encapsulated chromaffin cells released continuously catehcolamines and opioids peptides in vitro and in the CSF. Those results may prove chromaffin cell's anagesic effect indirectly.
Subject(s)
Animals , Rats , Acetone , Analgesia , Analgesics, Opioid , Capsules , Catecholamines , Cerebrospinal Fluid , Chromaffin Cells , Constriction , Drug Compounding , Enkephalin, Methionine , Immune System , Nicotine , Opioid Peptides , Peptides , Sciatic Nerve , Spinal Cord , Subarachnoid SpaceABSTRACT
The purpose of the present study was to examine the effect of naltrexone, an opioid antagonist, on secretion of catecholamines (CA) evoked by cholinergic nicotinic stimulation and membrane-depolarization from the isolated perfused rat adrenal gland and to establish the mechanism of its action. Naltrexone (3x10 (-6) M) perfused into an adrenal vein for 60 min produced time-dependent inhibition in CA secretory responses evoked by ACh (5.32x10 (-3) M), high K+ (5.6x10 (-2) M), DMPP (10 (-4) M) and McN-A-343 (10 (-4) M). Naltrexone itself did also fail to affect basal CA output. In adrenal glands loaded with naltrexone (3x10 (-6) M), the CA secretory responses evoked by Bay-K-8644, an activator of L-type Ca2+ channels and cyclopiazonic acid, an inhibitor of cytoplasmic Ca2+-ATPase, were also inhibited. However, in the presence of met-enkephalin (5x10 (-6) M), a well-known opioid agonist, the CA secretory responses evoked by ACh, high K+, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were also significantly inhibited. Collectively, these experimental results demonstrate that naltrexone inhibits greatly CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as that by membrane depolarization. It seems that this inhibitory effect of naltrexone does not involve opioid receptors, but might be mediated by blocking both the calcium influx into the rat adrenal medullary chromaffin cells and the uptake of Ca2+ into the cytoplasmic calcium store, which are at least partly relevant to the direct interaction with the nicotinic receptor itself.
Subject(s)
Animals , Rats , (4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride , 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester , Adrenal Glands , Adrenal Medulla , Calcium , Catecholamines , Chromaffin Cells , Cytoplasm , Dimethylphenylpiperazinium Iodide , Enkephalin, Methionine , Membranes , Naltrexone , Receptors, Nicotinic , Receptors, Opioid , VeinsABSTRACT
The present study was carried out in five cats which did not attack the rats spontaneously. Predatory attack on an anaesthetized rat was elicited by electrical stimulation of lateral hypothalamus at a mean current strength of 650 microA. The attack was accompanied by minimal affective display and culminated in neck biting. Microinfusions of DAME (delta-alanine methionine enkephaline) in 500 ng dose in substantia nigra facilitated the predatory attack and there was a significant reduction in the threshold current strength for affective display as well as somatomotor components. Microinfusions of naloxone, an opioid antagonist in 1.0 microg dose when DAME effect was at its peak reversed the facilitatory effects and the threshold returned to the control levels within 10 minutes of naloxone infusion at the same locus. Microinfusions of naloxone alone in similar dosage completely blocked the predatory attack response as indicated by an increase in the threshold current strength for somatomotor as well as affective display components. The somatomotor were completely inhibited and could not be elicited even when the current strength was increased to 1000 microA. Control injections of saline in similar volumes (0.5 microl) failed to produce any response Microinfusions of naloxone in lower dose (250 ng) failed to produce any blocking effect. These findings indicate that hypothalamically elicited predatory attack is facilitated by enkephalinergic mechanisms operating at the midbrain level.
Subject(s)
Aggression/drug effects , Animals , Cats , Dose-Response Relationship, Drug , Electric Stimulation , Electrodes, Implanted , Enkephalin, Methionine/administration & dosage , Enkephalins/administration & dosage , Female , Hypothalamus/anatomy & histology , Male , Microinjections , Naloxone/administration & dosage , Narcotic Antagonists/administration & dosage , Predatory Behavior/physiology , Substantia Nigra/anatomy & histologyABSTRACT
The goal of this study was to evaluate the anti-tumor activity of two Enkephalin analogues designed and synthesized using a conventional solution method. The anti-tumor activity of these two analogues was studied in-vitro following National cancer institute [NCI] protocol [USA]. The results confirmed that the synthesized Leu- Enkephalin analogue [analogue 1] have a positive effect on all cell lines tested indicating its effectiveness as anti-tumor compound on many cancers especially those of lungs, colon and breast. Met-Enkephalin analogue [ana1ogue II] showed no effect on any type of tumor cells tested. In conclusion analogue I can be considered as a novel promising anticancer compound
Subject(s)
Enkephalins , Enkephalins/analogs & derivatives , Antineoplastic Agents , Enkephalin, Leucine , Enkephalin, MethionineABSTRACT
OBJECTIVE: Adrenal medullary chromaffin cells are known to release analgesic substances such as opioides and catecholamines. Transplantation of them is a novel method that challenges current approaches in treating chronic pain. The transplantation of xenogeneic chromaffin cells into the central nervous system(CNS) supply antinociception in animals. In this study, we investigated the analgesic effects of rat adrenal medullary chromaffin cells transplanted into the CNS of the mouse. To study the antinociceptive efficacy of transplanted chromaffin cells, the survival of rat adrenal medullary chromaffin cells transplanted into the CNS of mouse was determined. METHODS: The adrenal medullary chromaffin cells isolated from rat were transplanted into the striatum of mouse. These cells were confirmed of the release of Met-enkephalin and Leu-enkephalin by HPLC, and immunoblots for tyrosine hydroxylase(TH). Two weeks after transplantation, we performed immunohistochemistry for TH to determine the survival of implanted cells and assessed pain sensitivity at the same time. RESULTS: The isolated rat adrenal medullary chromaffin cells were positive for anti-TH antibody and released Met-enkephalin and Leu-enkephalin more than rat endothelial cells. Transplanted rat chromaffin cells were stained with anti-TH antibody in striatum of mouse after 2 weeks. Pain sensitivity was reduced on the chromaffin cell-transplanted mouse compared to endothelial cell-transplanted mouse by the hot plate test. CONCLUSION: These results suggest that the rat chromaffin cells were suitably transplanted into the CNS of mouse. This approach could be used as a therapy for reducing of chronic pain induced by cancer or neuronal injury.
Subject(s)
Animals , Mice , Rats , Catecholamines , Chromaffin Cells , Chromatography, High Pressure Liquid , Chronic Pain , Endothelial Cells , Enkephalin, Leucine , Enkephalin, Methionine , Enkephalins , Immunohistochemistry , Neurons , TyrosineABSTRACT
Bipolar concentric electrodes were implanted in five cats in extreme lateral regions of hypothalamus. These sites were electrically stimulated using biphasic square wave pulses at a current strength ranging from 300-800 microA to evoke predatory attack on an anaesthetized but live rat. At lower current strength (300 microA) only alertness with pupillary dilatation was produced. Gradual increase in the current strength led to the recruitment of somatic and affective components and a predatory attack was exhibited at a mean current strength of 700 microA. A scoring system allowed the construction of stimulus response curves, which remained fairly constant when repeated over a period of 3-4 weeks. Bilateral microinjections of delta-alanine methoinine enkephaline (DAME) (500 ng in 0.5 microliter saline) in ventrolateral tegmental area (VTA) elevated the mean threshold current strength for affective components while somatomotor components were totally inhibited. The blocking effect of DAME persisted for 1 hour. Microinjections of naloxone (1 microgram) in similar volumes facilitated the response as indicated by a reduction in threshold current strength for somatomotor and affective components. Microinjections of naloxone (1 microgram) in similar volumes facilitated the response as indicated by a reduction in threshold current strength for somatomotor and affective components. Microinjections of naloxone (1 microgram) also reversed the blocking effect of DAME and the thresholds returned to the control level within 10 min while microinjection of normal saline as control had no effect. The excitatory effects of naloxone and inhibitory effects of DAME were statistically significant at P < 0.01 and P < 0.05 respectively with Wilcoxon's signed rank test. The present study indicates that enkephalinergic as well as opioidergic mechanisms operating at the midbrain (VTA) level are involved in the inhibition of predatory attack as elicited from lateral hypothalamus.
Subject(s)
Animals , Cats , Drug Interactions , Electric Stimulation , Electrodes, Implanted , Enkephalin, Methionine/administration & dosage , Enkephalins/physiology , Female , Hypothalamus/drug effects , Male , Microinjections , Naloxone/administration & dosage , Narcotic Antagonists/administration & dosage , Predatory Behavior/drug effects , Rats , Staining and Labeling , Ventral Tegmental Area/drug effectsABSTRACT
A complete normal coordinate analysis of Met5- and Leu5-enkephalins using Wilson's GF matrix method and Urey Bradley force field has been carried out to understand the dynamical behaviour of enkephalins. In addition, the charge distributions on different atoms of the two enkephalins and morphine using CNDO/2 method are also reported. The similarity in the charge distribution on the part of these two molecules is indicative of the possible interactions at the same receptor site as that of morphine and its derivatives. Apart from the topographical features and charge distribution, binding onto receptor site is not a static but a dynamic process and low frequency modes must play an important role in the recognition process. The significance of the out-of-plane amide VII band and other skeletal modes as characteristic of conformational states of Met5- and Leu5-enkephalins are discussed.
Subject(s)
Enkephalin, Leucine/metabolism , Enkephalin, Methionine/metabolism , Models, Molecular , Morphine/metabolism , Receptors, Opioid/metabolismABSTRACT
This study included 50 patients with pure bilharziasis and mixed liver cirrhosis at different clinical stages. They were selected from Inpatient Medical Department, Mansoura University Hospital. Ten healthy individuals were selected as a control group Leucine- and Methionine - enkephalins plasma levels were estimated in all the participants and after their classification into the following groups: group of intestinal billharziasis [10 patients], non - ascetic group [10 BHF patients + 12 patients with mixed cirrhosis] and ascetic group [8 BHF patients + 12 patients with mixed cirrhosis]. This study was shown that plasma enkephalins level is significantly increased in ascetic than in non- ascetic group of patients and this increase is proportional to the degree of derangement of hepatic function