Clinical and Experimental Pharmacology and Physiology最新文献

{"title":"Renal functional recovery among inpatients: A plausible marker of reduced renal functional reserve.","authors":"Yuri Gorelik,&nbsp;Mogher Khamaisi,&nbsp;Zaid Abassi,&nbsp;Roger G Evans,&nbsp;Samuel N Heyman","doi":"10.1111/1440-1681.13545","DOIUrl":"https://doi.org/10.1111/1440-1681.13545","url":null,"abstract":"<p><p>Renal functional reserve (RFR) reflects the ability of the kidney to enhance glomerular filtration rate (GFR) in response to a protein load. Chronic kidney disease (CKD) leads to diminished RFR, since the capacity for whole-body GFR to increase through hyperfiltration of remaining nephrons is limited. Evaluating 41,456 inpatients following computerised tomography we reported many exhibiting acute kidney injury (AKI) but more patients with recovering kidney function (AKR), presumably reflecting resolution of their critical conditions. The incidences of AKI and AKR were closely co-associated and were both inversely correlated with baseline kidney function. We discuss this phenomenon, arguing that AKR among inpatients with an acute illness, like AKI, may often reflect underlying subtle CKD with diminished RFR.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"48 12","pages":"1724-1727"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39434822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardioprotective effects of the proline-rich oligopeptide Bj-PRO-7a in spontaneously hypertensive rats.","authors":"Érika Fernandes de Jesus,&nbsp;Allancer Divino de Carvalho Nunes,&nbsp;Carolina Nobre Ribeiro Pontes,&nbsp;Larissa Matuda Macedo,&nbsp;Elizabeth Pereira Mendes,&nbsp;Danielle Alves Ianzer,&nbsp;Michael da Costa,&nbsp;Paulo César Ghedini,&nbsp;Fernanda Cristina Alcantara Dos Santos,&nbsp;Manoel Francisco Biancardi,&nbsp;Carlos Henrique Castro","doi":"10.1111/1440-1681.13577","DOIUrl":"https://doi.org/10.1111/1440-1681.13577","url":null,"abstract":"<p><p>The proline-rich oligopeptide from Bothrops jararaca snake venom, Bj-PRO-7a, promotes acute effects in blood pressure in hypertensive animals. However, the cardiac effects of this heptapeptide are completely unknown. Thus, we sought to evaluate whether the Bj-PRO-7a could protect against cardiac remodelling in spontaneously hypertensive rats (SHR). SHR were treated with Bj-PRO-7a (71 nmol/kg/day, s.c.) or saline for 28 days. Wistar rats were used as control. Systolic blood pressure (SBP) and heart rate (HR) were measured by tail-cuff plethysmography. Cardiomyocyte diameter and interstitial and perivascular fibrosis of the left ventricle (LV) were evaluated using Picrosirius staining. Immunofluorescence was used to detect collagen I and III. Fibroblast proliferation was assessed by immunohistochemistry to detect proliferating cell nuclear antigen (PCNA). Protein expression was assessed by western blot. The superoxide dismutase and catalase activities and the concentration of lipid peroxidation products were evaluated in the LV. The SBP and HR were not different between treated and non-treated SHR at the end of the treatment. However, Bj-PRO-7a attenuated the cardiomyocyte hypertrophy, deposition of interstitial and perivascular fibrosis and collagen I, and positive PCNA-labelled fibroblasts. This peptide also reduced the increased levels of TBARS, expression and activity of catalase, and activity of SOD in LV from SHR. Also, the Bj-PRO-7a increased the expression of metalloproteinases-2 in SHR hearts. These findings demonstrate that the Bj-PRO-7a reduced the pathological cardiac remodelling in a pressure-independent manner in hypertensive rats through mechanisms mediated by oxidative stress regulation.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"48 12","pages":"1693-1703"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13577","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39339849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Azathioprine pretreatment ameliorates myocardial ischaemia reperfusion injury in diabetic rats by reducing oxidative stress, apoptosis, and inflammation.","authors":"Cuijie Lu,&nbsp;Ling Liu,&nbsp;Shuai Chen,&nbsp;Junfei Niu,&nbsp;Sheng Li,&nbsp;Wenxian Xie,&nbsp;Xiang Cheng","doi":"10.1111/1440-1681.13569","DOIUrl":"https://doi.org/10.1111/1440-1681.13569","url":null,"abstract":"<p><p>This study was presented to observe the therapeutic effects of azathioprine (AZA) pretreatment on myocardial ischaemia reperfusion (I/R) damage in diabetic rats. All rats were randomly separated into control + sham operation; control +I/R; diabetes mellitus (DM) +I/R and DM +I/R + AZA groups. Diabetic rat models were established by intraperitoneally injecting 60 mg/kg streptozotocin (STZ). Diabetic rats were given 3 mg/kg AZA daily by gavage for 5 days. Then, myocardial I/R rat models were constructed. Myocardial infarction size and myocardial damage were respectively detected by TTC and H&E staining. Cardiac injury markers (CK-MB and MPO) and oxidative stress factors (SOD and MDA) were measured via ELISA. The protein expression of apoptotic markers (Caspase8, Caspase3, BAX and Bcl2), inflammatory factors (TLR4 and TNF-α) and AKT1/GSK3β in myocardial tissues was measured by western blot, immunohistochemistry or immunofluorescence. Data showed that AZA pretreatment could lessen myocardial infarction size and myocardial damage, and could down-regulate serum CK-MB, MPO, SOD and MDA levels in diabetic rats under I/R. Furthermore, AZA pretreatment decreased Caspase8, Caspase3, BAX, TLR4 and TNF-α expression, and increased Bcl2 expression in myocardial tissues of diabetic rats following I/R. Also, AZA pretreatment lowered AKT1, p-AKT1, GSK3β and p-GSK3β expression in diabetic heart after I/R. This study found that AZA may reduce myocardial injury in diabetic rats following I/R via reducing oxidative stress, cardiomyocyte apoptosis, and inflammatory response, which could be related to AKT1/GSK3β pathway inactivation.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"48 12","pages":"1621-1632"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13569","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39303467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3-O-Acetyl-11-keto-β-boswellic acid ameliorates chronic unpredictable mild stress induced HPA axis dysregulation in relation with glutamate/GABA aberration in depressive rats.","authors":"Venkatesh Gunasekaran,&nbsp;Anitta Augustine,&nbsp;Jinu Avarachan,&nbsp;Abdul Khayum,&nbsp;Arivukkarasu Ramasamy","doi":"10.1111/1440-1681.13567","DOIUrl":"https://doi.org/10.1111/1440-1681.13567","url":null,"abstract":"<p><p>Overt expression of brain glucocorticoid receptor (GR) leads to elevation of glutamate release causes cerebral excitotoxicity which in turn produce neuropsychological disorders. The aim of our work is to study the consequence of 3-O-Acetyl-11-keto-β-boswellic acid (AKBA) on chronic unpredictable mild stress (CUMS) induced HPA axis dysregulation in relative to glutamate and GABA irregularity in depressive rats. AKBA (5, 10 &15mg/kg) was administered for 28 days parallel with CUMS induction in rats. Behavioural studies, tail suspension test (TST), open field exploratory (OFT) and forced swim test (FST) were performed. Biochemical studies including plasma corticosterone, glutamate GABA and glutamic acid decarboxylase (GAD) enzyme activity were studied. Glucocorticoid receptor expression and brain histology were studied to observe the effect of AKBA. CUMS induction results in depressive state of the animals were confirmed by the sucrose preference test. The administration of AKBA significantly reduced the immobility time and improved the exploratory behaviour. Plasma corticosterone and brain glutamate level was decreased and GABA level were increased significantly evident with GAD activation in AKBA-treated animals, further confirmed with decreased GR expression improves architecture of prefrontal cortex region. Correlation study illustrates behavioural improvements undeviating the biochemical alteration and GR expression after AKBA treatment during depression. AKBA significantly reversed the CUMS-induced glutamate/GABA abnormalities through the adaptation of central HPA axis regulation. Hence this study concludes that AKBA can be a better alternative to treat depressive disorders.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"48 12","pages":"1633-1641"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13567","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39270978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nimodipine reduces delayed cerebral vasospasm after intracranial tumour surgery: A Retrospective Study.","authors":"Ying Yu,&nbsp;Yunqian Li,&nbsp;Zheng Jin,&nbsp;Shuai Zhao,&nbsp;Xuan Xie,&nbsp;Fan Chen","doi":"10.1111/1440-1681.13564","DOIUrl":"https://doi.org/10.1111/1440-1681.13564","url":null,"abstract":"<p><p>Cerebral vasospasm (CVS) is a frequent and serious neurosurgical complication, without sufficient therapy. This retrospective study was performed to analyze if nimodipine can improve prognosis and reduce ischaemia secondary to delayed CVS after intracranial tumour surgery. A retrospective review was performed over the years 2011 to 2012 for patients with an anterior cranial fossa tumour and underwent intracranial tumour surgery. The surgical field was soaked with nimodipine solution or normal saline. Transcranial Doppler ultrasonography was used to measure velocity in the middle cerebral artery (MCA) and the distal extracranial internal carotid artery (eICA). Follow-up was performed using the Glasgow Outcome Scale (GOS) after discharge. There were 94 patients that met the inclusion criteria. They included 50 males and 44 females, with a mean age of 49.6 years. In the nimodipine group, CVS occurred in 13 patients; 9 patients had CVS between 4 and 7 days, and 4 had CVS between 8 and 14 days. In the normal saline group, 19 patients had CVS, 3 presented with CVS within 3 days, 11 between 4-7 days and 5 between 8-14 days. A significant difference in the occurrence of CVS was observed between the two groups. Preoperative and postoperative the MCA velocities were compared, revealing a significant change in the normal saline group but not in the nimodipine group. Nimodipine markedly improves prognosis and significantly reduces ischaemia secondary to delayed CVS after intracranial tumour surgery, as well as the risks of mortality and morbidity.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"48 12","pages":"1613-1620"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13564","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39270979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crosstalk between AdipoR1/AdipoR2 and Nrf2/HO-1 signal pathways activated by β-caryophyllene suppressed the compound 48/80 induced pseudo-allergic reactions.","authors":"Manash Pratim Pathak,&nbsp;Pompy Patowary,&nbsp;Aparoop Das,&nbsp;Danswrang Goyary,&nbsp;Sanjeev Karmakar,&nbsp;Yangchen D Bhutia,&nbsp;Probin Kumar Roy,&nbsp;Sanghita Das,&nbsp;Pronobesh Chattopadhyay","doi":"10.1111/1440-1681.13555","DOIUrl":"https://doi.org/10.1111/1440-1681.13555","url":null,"abstract":"<p><p>Mast cell activation is initiated by two signalling pathways: immunoglobulin E (IgE)-dependent and IgE-independent pathway. It is reported that the IgE-independent type or pseudo-allergy pathway gets activated by G-protein-dependent activation of the mast cell. Recently, adiponectin (APN) receptors, AdipoR1, and AdipoR2 have been identified as G-protein-coupled receptors (GPCRs). Interestingly, APN replenishment is reported to activate the Nrf2/HO-1 signalling axis. However, no study has been performed interlinking the role of APN and the Nrf2/HO-1 signalling axis in pseudo-allergic reaction. In the present study, we evaluated the anti-pseudo-allergic effects of β-caryophyllene, an FDA-approved food additive, in activating AdipoR1/AdipoR2 and Nrf2/HO-1 axis signalling pathway. Compound 48/80 (C48/80)-induced systemic and cutaneous anaphylaxis-like shock in BALB/c mice was performed to assess the efficacy of β-caryophyllene (BCP). To assess the effect of BCP in anaphylactic hypotension, mean arterial pressure was measured in Wistar rats. Inhibitory properties of BCP in mast cell degranulation were estimated in rat peritoneal mast cells (RPMCs). ELISA was performed to estimate interleukin (IL)-6, tumour necrosis factor (TNF), IL-1β, IgE, ovalbumin (OVA)-IgE and APN and western blotting for protein expression of Nrf2/HO-1 and AdipoR1-AdipoR2. BCP dose-dependently inhibited systemic and cutaneous anaphylaxis-like shock induced by C48/80. BCP dose-dependently inhibited the mast cell degranulation followed by inhibition of histamine release. Also BCP dose-dependently activated the Nrf2/HO-1 and AdipoR1-AdipoR2 signalling axis pathway. Moreover, BCP reversed the drop in blood pressure when the haemodynamic parameters were accessed. Our findings suggest that BCP is a potent AdipoR1/AdipoR2-Nrf2/HO-1 axis pathway agonist that may suppress the IgE-independent pathway towards allergic response to secretagogues.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"48 11","pages":"1523-1536"},"PeriodicalIF":0.0,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13555","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39226296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ICOS⁺ follicular regulatory T cells are implicated in the pathogenesis of ulcerative colitis.","authors":"Li Yao,&nbsp;Jianyang Guo,&nbsp;Juan Gui,&nbsp;Feihu Bai,&nbsp;Ruijuan Xin,&nbsp;Yanhong Deng,&nbsp;Shaoxuan Wang,&nbsp;Haitao Li","doi":"10.1111/1440-1681.13568","DOIUrl":"https://doi.org/10.1111/1440-1681.13568","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) with a rising incidence worldwide. The precise aetiology is unclear, but aberrant regulatory T cell (Treg) responses have been documented in active UC patients. Follicular regulatory T cell (Tfr) is a recently identified subset of Treg cells. In this study, the role of ICOS in Tfr cells, which is a costimulatory molecule shown to stabilize and promote Treg differentiation, was investigated in UC patients. We found that with increasing UC severity, the frequency of ICOS⁺ CD4 T cells was increased, but the level of ICOS expression by ICOS⁺ CD4 T cells was decreased. ICOS⁺ cells were highly enriched in follicular regulatory T cells (Tfr), which is a subset of Treg cells characterized by CD25⁺ CD127^- CXCR5⁺ Foxp3⁺ phenotype. Anti-CD3, anti-CD3/CD28, or anti-CD3/ICOS had all significantly increased the expression of Foxp3 and IL-10, and among the three stimulation methods, anti-CD3/ICOS was most effective at enhancing Foxp3 and IL-10 expression. Moreover, anti-CD3/ICOS-stimulated Tfr cells could suppress conventional T cell proliferation in an IL-10-dependent manner. Interestingly, anti-CD3/ICOS stimulation was less effective in UC-Mild and UC-Active patients compared to that in healthy and UC-Remission patients. In addition, UC patients presented impairment in ICOS upregulation following anti-CD3 stimulation. Overall, these data indicated that ICOS⁺ Tfr cells were dysregulated in UC patients and the level of dysregulation was associated with the severity of UC, suggesting that ICOS⁺ Tfr cells could serve as a biomarker of the progression of UC.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"48 11","pages":"1566-1575"},"PeriodicalIF":0.0,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39287490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of mirabegron on obesity-induced inflammation and insulin resistance are associated with brown adipose tissue activation but not beiging in the subcutaneous white adipose tissue.","authors":"Carmem Peres Valgas da Silva,&nbsp;Fabiano Calmasini,&nbsp;Eduardo Costa Alexandre,&nbsp;Helena Fonseca Raposo,&nbsp;Maria Andreia Delbin,&nbsp;Fabiola Zakia Monica,&nbsp;Angelina Zanesco","doi":"10.1111/1440-1681.13566","DOIUrl":"https://doi.org/10.1111/1440-1681.13566","url":null,"abstract":"<p><p>Mirabegron is a selective β₃-adrenergic receptors agonist, which has been recently shown to improve metabolic health in rodents and humans. In this study, we investigated the effects of 2-week mirabegron treatment on the metabolic parameters of mice with a diet-induced obesity (DIO). C57BL/6JUnib mice were divided into control (CTR) and obese (OB) groups treated with vehicle, and an OB group treated with mirabegron (OB + MIRA). The obese groups were fed a high-fat diet for 12 weeks. Mirabegron (10 mg/kg/day) was administrated orally by gavage from weeks 10-12. After 2 weeks of mirabegron treatment, the energy expenditure was assessed with indirect calorimetry. Blood glucose, insulin, glycerol, free fatty acids (FFA), thiobarbituric acid reactive substance (TBAR), and tumour necrosis factor (TNF)-α levels were also assessed, and the HOMA index was determined. Liver tissue, brown adipose tissue (BAT), and inguinal white adipose tissue (iWAT) samples were collected for histological examination. The protein expressions of uncoupling protein 1 (UCP1) and mitochondrial transcription factor A (TFAM) were assessed using western blotting of the BAT and iWAT samples. In this study, mirabegron increased the energy expenditure and decreased adiposity in OB + MIRA. Increased UCP1 expression in BAT without changes in iWAT was also found. Mirabegron decreased circulating levels of FFA, glycerol, insulin, TNF-α, TBARS and HOMA index. DIO significantly increased the lipid deposits in the liver and BAT, but mirabegron partially reversed this change. Our findings indicate that treatment with mirabegron decreased inflammation and improved metabolism in obese mice. This effect was associated with increased BAT-mediated energy expenditure, but not iWAT beiging, which suggests that mirabegron might be useful for the treatment of obesity and diabetes.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"48 11","pages":"1477-1487"},"PeriodicalIF":0.0,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13566","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39270976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myrtenol complexed with β-cyclodextrin ameliorates behavioural deficits and reduces oxidative stress in the reserpine-induced animal model of Parkinsonism.","authors":"Suellen Silva-Martins,&nbsp;Jose Ivo Araújo Beserra-Filho,&nbsp;Amanda Maria-Macêdo,&nbsp;Ana Cláudia Custódio-Silva,&nbsp;Beatriz Soares-Silva,&nbsp;Sara Pereira Silva,&nbsp;Rafael Herling Lambertucci,&nbsp;Regina Helena Silva,&nbsp;José Ronaldo Dos Santos,&nbsp;Sathiyabama Rajiv Gandhi,&nbsp;Lucindo José Quintans-Júnior,&nbsp;Alessandra Mussi Ribeiro","doi":"10.1111/1440-1681.13563","DOIUrl":"https://doi.org/10.1111/1440-1681.13563","url":null,"abstract":"Current pharmacological approaches to treat Parkinson’s disease have low long‐term efficacy and important adverse side effects. The development of new pharmacological therapies has focused on novel plant‐derived phytochemicals. The alcoholic monoterpene myrtenol has been isolated from several plant species, and has anxiolytic, analgesic, anti‐inflammatory and antioxidant actions. Our study evaluated the neuroprotective potential of myrtenol complexed with β‐cyclodextrin (MYR) on a progressive parkinsonism model induced by reserpine (RES) in mice. The complexation with cyclodextrins enhances the pharmacological action of monoterpenes. Male Swiss mice were treated daily with MYR (5 mg/kg, p.o.) and with RES (0.1 mg/kg, s.c.) every other day during 28 days. Behavioural evaluations were conducted across treatment. At the end of the treatment, immunohistochemistry for tyrosine hydroxylase (TH) and oxidative stress parameters were evaluated. Chronic MYR‐treatment protected against olfactory sensibility loss, restored short‐term memory and decreased RES‐induced motor impairments. Moreover, this treatment prevented dopaminergic depletion and reduced the oxidative status index in the dorsal striatum. Therefore, MYR ameliorated motor and non‐motor impairments in the progressive animal model of parkinsonism, possibly by an antioxidant action. Additional research is needed to investigate the mechanisms involved in this neuroprotective effect.","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"48 11","pages":"1488-1499"},"PeriodicalIF":0.0,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13563","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39277012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"General anaesthetics as 'awakening agents'? Re-appraising the evidence for suggested 'pressure reversal' of anaesthesia.","authors":"Ben M George,&nbsp;Jaideep J Pandit","doi":"10.1111/1440-1681.13554","DOIUrl":"https://doi.org/10.1111/1440-1681.13554","url":null,"abstract":"<p><p>Increasing ambient pressure has been suggested to reverse general anaesthesia and provides support for the 'lipid theory'. Anaesthetic dissolution into cell membranes is said to cause their expansion to a critical volume. This triggers a sequence of events as basis of a unitary theory of anaesthestic mechanism. Pressure is argued to restore membrane volume to below critical level, reversing this process. We wished to review the original literature to assess internal consistency within and across papers, and to consider if alternative interpretations were possible. A literature search yielded 31 relevant 'pressure reversal' papers for narrative review, and 8 papers that allowed us to re-plot original data more consistently as 'dose-response' curves for the anaesthetics examined. Original studies were heterogenous for end-points, pressure ranges, species, and agents. Pressure effects were inconsistent, with narcosis at certain pressures and excitation at others, influenced by carrier gas (e.g., nitrogen vs helium). Pressure reversal (a right- or downward-shift on the re-plotted dose-response curves) was evident, but only in some species and at certain pressures and anaesthetic concentrations. However, even more striking was a novel 'awakening' effect of anaesthetics: i.e., anaesthetics reversed the narcotic effect of pressure, but this was limited to certain pressures at generally low anaesthetic concentrations. Contrary to the established view, 'pressure reversal' is not a universal phenomenon. The awakening effect of anaesthetics - described here for the first time - has equal evidence to support it, within the same literature, and is something that cannot be fully explained. Pressure cannot meaningfully be used to gain insight into anaesthetic mechanisms because of its heterogenous, non-specific and unpredictable effects on biological systems.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"48 11","pages":"1454-1468"},"PeriodicalIF":0.0,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13554","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39222821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}