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Therapeutic Approaches to Post-Mastectomy Pain Syndrome

Journal of Biosciences and Medicines 2023年第12期11卷 304-317页

作者： Vanessa Ferreira Dias Duarte Da Costa Giovanna Schwarz Mazzucca Carlos Augusto Pires Zerbini Oscar César Pires Camila Dos Santos Leite Laboratory of pharmacology and physiology Department of Medicine Taubaté University Taubaté Brazil

Background: Breast cancer is increasingly common in society and post-mastectomy pain is a striking condition associated with surgery, both intra and postoperatively. The post-mastectomy syndrome is characterized by the persistence of pain for more than 3 months after the procedure. It is mostly of neuropathic origin and is highly refractory to treatments, which vary from clinical to surgical measures and alternative techniques. In this context, it is essential to understand the possible approaches to these patients. Objective: Understand alternatives for pain management in patients undergoing mastectomy, especially in those in whom pain persists for more than 3 months. Methods: Systematic literature review, conducted in the Virtual Health Library databases includes: Lilacs, SciELO, Medline, PubMed and Cochrane between 2018 and 2023, restricted to articles in English with the descriptors: Mastectomy, chronic Pain, Nerve Blocks and Breast Cancer. 317 articles were found involving the descriptors presented, all in English. After reading the abstracts, 28 articles were selected. Results: This review analyzed 28 scientific studies that rigorously met the previously established characteristics in the sample selection. The synthesis included the following aspects: author/year of publication, article title, objective, type of study and database. Conclusion: It was concluded that, according to the analyzed studies, post-mastectomy pain is a problem that has increased its incidence and that needs the attention of health professionals. The use of antineuropathic medications, nerve blocks, fat grafting, lymph node transplantation, therapy, physical activity and acupuncture are some examples of therapeutic approaches for these women. Therefore, the team must assist the patients, seeking to provide a better prognosis, quality of life and comfort.

关键词： Mastectomy Chronic Pain Nerve Blocks Breast Cancer

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Silencing Fas-associated phosphatase 1 expression enhances efficiency of chemotherapy for colon carcinoma with oxaliplatin

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World Journal of Gastroenterology 2010年第1期16卷 112-118页

作者： Navada Eagleton Department of Veterinary physiology and pharmacology Texas A&M UniversityCollege Station

AIM:To investigate whether silencing Fas-associated phosphatase 1(FAP-1)expression enhances the efficiency of chemotherapy for colon carcinoma with ***:Expression of FAP-1 in mRNA and protein was detected by reverse transcription polymerase chain reaction(RT-PCR)and flow *** interfering RNA(siRNA)was designed according to the FAP-1 mRNA *** proliferation was evaluated by methyl thiazolyl tetrazolium(MTT)*** V-and propidine iodine(PI)were assayed by flow cytometry for the detection of apoptosis. RESULTS:The expression of FAP-1 was increased in SW480 cells after chemotherapy with oxaliplatin. Transfection of FAP-1 siRNA into SW480 cells silenced the expression of FAP-1 and consequently abolished the inhibitory function of Fas/FasL-mediated apoptosis pathway,thus increasing the efficacy of chemotherapy for colon carcinoma with oxaliplatin. CONCLUSION:RNA interference combined with conventional chemotherapy is more effective against colon cancer.

关键词： Colon carcinoma Fas-associated phosphatase 1 RNA interference Oxaliplatin Chemotherapy

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Unmasking the responses of the stem cells and progenitors in the subventricular zone after neonatal and pediatric brain injuries

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Neural Regeneration Research 2016年第1期11卷 45-48页

作者： Mariano Guardia Clausi Ekta Kumari Steven W.Levison Department of pharmacology Physiology and Neuroscience Rutgers-New Jersey Medical School

There is great interest in the regenerative potential of the neural stem cells and progenitors that populate the subventricular zone（SVZ）. However, a comprehensive understanding of SVZ cell responses to brain injuries has been hindered by the lack of sensitive approaches to study the cellular composition of this niche. Here we review progress being made in deciphering the cells of the SVZ gleaned from the use of a recently designed flow cytometry panel that allows SVZ cells to be parsed into multiple subsets of progenitors as well as putative stem cells. We review how this approach has begun to unmask both the heterogeneity of SVZ cells as well as the dynamic shifts in cell populations with neonatal and pediatric brain injuries. We also discuss how flow cytometric analyses also have begun to reveal how specific cytokines, such as Leukemia inhibitory factor are coordinating SVZ responses to injury.

关键词： CNS regeneration cytokines glial progenitors gliogenesis inflammation cerebral palsy traumatic brain injury stroke

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Muscle secretion of toxic factors,regulated by miR126-5p,facilitates motor neuron degeneration in amyotrophic lateral sclerosis

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Neural Regeneration Research 2019年第6期14卷 969-970页

作者： Roy Maimon Eran Perlson Department of physiology and pharmacology Sackler Faculty of MedicineTel Aviv University

Amyotrophic lateral sclerosis(ALS)is a lethal neurodegenerative disease characterized by neuromuscular junction(NMJ)disruption,motor neuron(MN)axon degeneration,and neuronal ***,there is currently no effective treatment available for ALS and consequently,most patients die several years post *** neurodegeneration that occurs in ALS is considered to be a non-cell autonomous process involving interactions between the motor neuron and its diverse extracellular microenvironments via an unknown *** Axonopathy is one of the early disease signs;however,the involvement and contribution of neighboring tissues and specifically,the muscle environment to the disease pathology remain *** works have concluded that muscles play a minor role or none at all in ALS pathology.

关键词： Muscle secretion toxic factors facilitates motor

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Expression of connexin 30 and connexin 32 in hippocampus of rat during epileptogenesis in a kindling model of epilepsy

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Neuroscience Bulletin 2012年第6期28卷 729-736页

作者： Bijan Akbarpour Mohammad Sayyah Vahab Babapour Reza Mahdian Siamak Beheshti Ahmad Reza Kamyab departments of physiology and pharmacology Pasteur Institute of Iran.Tehran 131694-3551Islamic Republic of Iran Department of physiology Faculty of Veterinary MedicineIslamic Azad UniversityScience and Research BranchTehran 14778-93855Islamic Republic of Iran departments of physiology and pharmacology Pasteur Institute of IranTehran 131694-3551Islamic Republic of Iran Department of physiology Faculty of Veterinary MedicineTehran UniversityTehran 141996-31111Islamic-Republic of Iran Department of Molecular Medicine Biotechnology Research CenterPasteur Institute of Iran Department of Biology Faculty of Science University of IsfahanIsfahan 81746-73441Islamic Republic of Iran

Objective Understanding the molecular and cellular mechanisms underlying epileptogenesis yields new in- sights into potential therapies that may ultimately prevent epilepsy. Gap junctions （GJs） create direct intercellular conduits between adjacent cells and are formed by hexameric protein subunits called connexins （Cxs）. Changes in the expression of Cxs affect GJ communication and thereby could modulate the dissemination of electrical discharges. The hippocampus is one of the main regions involved in epileptogenesis and has a wide network of GJs between different cell types where Cx30 is expressed in astrocytes and Cx32 exists in neurons and oligodendrocytes. In the present study, we evaluated the changes of Cx30 and Cx32 expression in rat hippocampus during kindling epileptogenesis. Methods Rats were stereotaxically implanted with stimulating and recording electrodes in the basolateral amygdala, which was electrically stimulated once daily at afterdischarge threshold. Expression of Cx30 and Cx32, at both the mRNA and protein levels, was measured in the hippocampus at the beginning, in the middle （after acquisition of focal seizures）, and at the end （after establishment of generalized seizures） of the kindling process, by real-time PCR and Western blot. Results Cx30 mRNA expression was upregulated at the beginning of kindling and after acquisition of focal seizures. Then it was downregulated when the animals acquired generalized seizures. Overexpression of Cx30 mRNA at the start of kindling was consistent with the respective initial protein increase. Thereafter, no change was found in protein abundance during kindling. Regarding Cx32, mRNA expression decreased after acquisition of generalized seizures and no other significant change was detected in mRNA and protein abundance during kindling. Conclusion We speculate that Cx32 GJ communication in the hip- pocampus does not contribute to kindling epileptogenesis. The Cx30 astrocytic network localized to perivascular re

关键词： connexin 30 connexin 32 hippocampus kindling

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Better together? Treating traumatic brain injury with minocycline plus N-acetylcysteine

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Neural Regeneration Research 2022年第12期17卷 2589-2592页

作者： Siobhán Lawless Peter J.Bergold Graduate Program in Neural and Behavioral Sciences State University of New York-Downstate Health Sciences UniversityBrooklynNYUSA Department of physiology and pharmacology State University of New York-Downstate Health Sciences UniversityBrooklynNYUSA

Traumatic brain injury has a complex pathophysiology that produces both rapid and delayed brain damage. Rapid damage initiates immediately after injury. Treatment of traumatic brain injury is typically delayed many hours, thus only delayed damage can be targeted with drugs. Delayed traumatic brain injury includes neuroinflammation, oxidative damage, apoptosis, and glutamate toxicity. Both the speed and complexity of traumatic brain injury pathophysiology present large obstacles to drug development. Repurposing of Food and Drug Administration-approved drugs may be a highly efficient approach to get therapeutics to the clinic. This review examines the preclinical outcomes of minocycline and N-acetylcysteine as individual drugs and compares them to the minocycline plus N-acetylcysteine combination. Both minocycline and N-acetylcysteine are Food and Drug Administration-approved drugs with pleiotropic therapeutic effects. As individual drugs, minocycline and N-acetylcysteine are well tolerated, with known pharmacokinetics, and enter the brain through an intact blood-brain barrier. At concentrations greater than needed for antimicrobial action, minocycline is a potent anti-inflammatory minocycline, also acts as an antioxidant and inhibits multiple enzymes that promote brain injury including metalloproteases, caspases, and polyADP-ribose-polymerase-1. N-acetylcysteine alone is also an antioxidant. It increases brain glutathione, prevents lipid oxidation, and protects mitochondria. N-acetylcysteine also acts as an anti-inflammatory as well as increases extracellular glutamate by activating the X;cystine-glutamate antitransporter. These multiple actions of minocycline and N-acetylcysteine have made them attractive candidates to treat traumatic brain injury. When first dosed within the one hour after injury, either minocycline or N-acetylcysteine improves a diverse set of therapeutic outcome measures in multiple traumatic brain injury animal models. A small number of clinical

关键词： clinical trial outcome measures preclinical testing rodent models of traumatic brain injury therapeutic time window

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Metabolic Stress Hormone FGF21:From physiology to pharmacology

Metabolic Stress Hormone FGF21:From Physiology to Pharmacolo...

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第三届中国生物物理学会代谢生物学分会学术研讨会

作者： Steven Kliewer David Mangelsdorf departments of Molecular BiologyUniversity of Texas Southwestern Medical Center departments of pharmacology University of Texas Southwestern Medical Center departments of Howard Hughes Medical Institute University of Texas Southwestern Medical Center

＜正＞Fibroblast growth factor 21 （FGF21） is an unusual member of the FGF family that can circulate in the blood as a *** liver,FGF21 is induced by diverse nutritional stresses including alcohol,simple sugars and high fat/low carbohydrate"ketogenic"diets,which can all cause ***21 released into the blood stimulates thirst and suppresses further intake of alcohol and sugar.

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Safety and efficacy of purified clinoptilolite-tuff treatment in patients with irritable bowel syndrome with diarrhea:Randomized controlled trial

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World Journal of Gastroenterology 2022年第46期28卷 6573-6588页

作者： Karolina Anderle Michael Wolzt Gabriele Moser Bettina Keip Johannes Peter Claudia Meisslitzer Ghazaleh Gouya Michael Freissmuth Cornelius Tschegg Department of Clinical pharmacology Medical University of ViennaVienna 1090Austria Department of Internal Medicine III Division of Gastroenterology and HepatologyMedical University of ViennaVienna 1090Austria Glock Health Science and Research GmbHDeutsch-Wagram 2232Lower AustriaAustria Gouya Insights Vienna 1010Austria Institute of pharmacology and the Gaston H.Glock Research Laboratories for Exploratory Drug Development Center of Physiology and PharmacologyMedical University of ViennaVienna 1090Austria

BACKGROUND Irritable bowel syndrome(IBS)is a highly prevalent gastrointestinal disorder with poor response to *** with predominant diarrhea(IBS-D)is accompanied by abdominal pain as well as high stool frequency and *** clinoptilolite-tuff(PCT),which is approved by the Food and Drug Administration for use as a dietary supplement with the brand name G-PUR®,has previously shown therapeutic potential in other indications based on its physical adsorption *** To assess whether symptoms of IBS-D can be ameliorated by oral treatment with *** In this randomized,placebo-controlled,double-blind pilot study,30 patients with IBS-D diagnosis based on Rome IV criteria were *** a 4-wk run-in phase,14 patients were randomized to receive a 12-wk treatment with G-PUR®(2 g three times daily),and 16 patients received *** relief from IBS-D symptoms as measured by the proportion of responders according to the Subject’s Global Assessment(SGA)of Relief was assessed as the primary *** the secondary outcomes,validated IBS-D associated symptom questionnaires,exploratory biomarkers and microbiome data were *** The proportions of SGA of Relief responders after 12 wk were comparable in both groups,namely 21%in the G-PUR®group and 25%in the placebo *** 4 wk of treatment,36%of patients in the G-PUR®group vs 0%in the placebo group reported complete or considerable *** improvement in daily abdominal pain was noted in 94%vs 83%(P=0.0353),and the median number of days with diarrhea per week decreased by 2.4 d vs 0.3 d in the G-PUR®and placebo groups,*** trends were observed for 50%of responders in the Bristol Stool Form *** trends were also noted for combined abdominal pain and stool consistency response and the Perceived Stress Questionnaire *** 64%in the G-PUR®group compared to 86%in the placebo group required rescue medication intake during the *** microbiome

关键词： Irritable bowel syndrome Diarrhea Functional gastrointestinal disorder Clinoptilolite Zeolite Treatment

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Neuroprotective effects of ginsenoside Rg1-induced neural stem cell transplantation on hypoxic-ischemic encephalopathy

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Neural Regeneration Research 2015年第5期10卷 753-759页

作者： Ying-bo Li Yan Wang Ji-ping Tang Di Chen Sha-li Wang Institute of Neuroscience Chongqing Medical University Department of physiology and pharmacology Loma Linda University

Ginsenoside Rgl is the major pharmacologically active component of ginseng, and is reported to have various therapeutic actions. To determine whether it induces the differentiation of neural stem cells, and whether neural stem cell transplantation after induction has therapeutic effects on hypoxic-ischemic encephalopathy, we cultured neural stem cells in 10-80 ~tM ginsenoside Rgl. Immunohistochemistry revealed that of the concentrations tested, 20 mM ginsenoside Rgl had the greatest differentiation-inducing effect and was the concentration used for subsequent exper- iments. Whole-cell patch clamp showed that neural stem cells induced by 20 jaM ginsenoside Rgl were more mature than non-induced cells. We then established neonatal rat models of hypox- ic-ischemic encephalopathy using the suture method, and ginsenoside Rgl-induced neural stem cells were transplanted via intracerebroventricular injection. These tests confirmed that neural stem cells induced by ginsenoside had fewer pathological lesions and had a significantly better behavioral capacity than model rats that received saline. Transplanted neural stem cells expressed neuron-specific enolase, and were mainly distributed in the hippocampus and cerebral cortex. The present data suggest that ginsenoside Rgl-induced neural stem cells can promote the partial recovery of complicated brain functions in models of hypoxic-ischemic encephalopathy.

关键词： nerve regeneration hypoxic-ischemic brain damage ginsenoside Rgl neural stem cells cell transplantation ceil differentiation cognition nerve reconstruction neural regeneration

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Green tea polyphenols inhibit testosterone production in rat Leydig cells

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Asian Journal of Andrology 2009年第3期11卷 362-370页

作者： Marina S. Figueiroa Juliany S. B. Cesar Vieira Disleide S. Leite Ruben C. O. Andrade Filho Fabiano Ferreira Patricia S. Gouveia Daniel P. Udrisar Maria I. Wanderley Department of physiology and pharmacology Federal University of Pernambuco 50607-901 Recife PE Brazil

This study investigated the acute effects of green tea extract （GTE） and its polyphenol constituents, （-）-epigallocatechin-3-gallate （EGCG） and （-）-epicatechin （EC）, on basal and stimulated testosterone production by rat Leydig cells in vitro. Leydig cells purified in a Percoll gradient were incubated for 3 h with GTE, EGCG or EC and the testosterone precursor androstenedione, in the presence or absence of either protein kinase A （PKA） or protein kinase C （PKC） activators. The reversibility of the effect was studied by pretreating cells for 15 min with GTE or EGCG, allowing them to recover for 1 h and challenging them for 2 h with human chorionic gonadotropin （hCG）, luteinizing hormone releasing hormone （LHRH）, 22（R）-hydroxycholesterol or androstenedione. GTE and EGCG, but not EC, inhibited both basal and kinase-stimulated testosterone production. Under the pretreatment conditions, the inhibitory effect of the higher concentration of GTE/EGCG on hCG/LHRH-stimulated or 22（R）- hydroxycholesterol-induced testosterone production was maintained, whereas androstenedione-supported testosterone production returned to control levels. At the lower concentration of GTE/EGCG, the inhibitory effect of these polyphenols on 22（R）-hydroxycholesterol-supported testosterone production was reversed. The inhibitory effects of GTE may be explained by the action of its principal component, EGCG, and the presence of a gallate group in its structure seems important for its high efficacy in inhibiting testosterone production. The mechanisms underlying the effects of GTE and EGCG involve the inhibition of the PKA/PKC signalling pathways, as well as the inhibition of P450 side-chain cleavage enzyme and 17β-hydroxysteroid dehydrogenase function.

关键词： green tea polyphenols Leydig cells protein kinase A protein kinase C testosterone

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