It is our contention that the concept of a probiotic as a living bacterium providing unspecified health benefits is inhibiting the development and establishment of an evidence base for the growing field of pharmacobio...It is our contention that the concept of a probiotic as a living bacterium providing unspecified health benefits is inhibiting the development and establishment of an evidence base for the growing field of pharmacobiotics.We believe this is due in part to the current regulatory framework,lack of a clear definition of a probiotic,the ease with which currently defined probiotics can be positioned in the market place,and the enormous profits earned for minimum investment in research.To avoid this,we believe the following two actions are mandatory:international guidelines by a forum of stakeholders made available to scientists and clinicians,patient organizations,and governments;public research funds made available to the scientific community for performing independent rigorous studies both at the preclinical and clinical levels.展开更多
Objective:To investigate the anti-proliferative effects of 20-hydroxyecdysone isolated from the bark of Dacrycarpus imbricatus(Blume) de Laub.Methods:Column chromatography was used for isolation of compounds from plan...Objective:To investigate the anti-proliferative effects of 20-hydroxyecdysone isolated from the bark of Dacrycarpus imbricatus(Blume) de Laub.Methods:Column chromatography was used for isolation of compounds from plant material.The structure of the isolated compound was identified by mass spectrometry and nuclear magnetic resonance techniques,including HSQC,HMBC,NOE-difference experiments.The isolated compound was tested for its anti-proliferative activity in acute myeloid leukemia(AML) and OCI-AML cells.Results:Compound 1 was isolated from the ethyl acetate fraction of Dacrycarpus imbricatus barks by column chromatography.Its chemical structure was identified as 20-hydroxyecdysone(20HE),a cholestane-type ecdysteroid,by a combination of mass spectrometry and nuclear magnetic resonance spectrometric analyses.Our goal was to test the anti-proliferative activity of 20 HE using the OCI-AML cell line.20 HE significantly decreased OCI cell number at a concentration of 1 mg/mL,whereas lower concentrations were ineffective.Moreover,this decrease was due to partial blockage of the G_1/S phase of the cell cycle,with a reduction of cells in the G_2M phase,not due to increased apoptosis.Conclusions:This indicates that 20 HE significantly decreases the number of cells in the G_1/S phase of the cell cycle in human AML cells.This is the first time that the anti-proliferative activity of 20 HE against a human tumor cell line has been reported.展开更多
[Objectives] To study the anti-inflammatory effects and its possible action mechanism of Pereskia aculeate Miller on rats with adjuvant arthritis( AJ). [Methods] Fifty SD rats( half male and half female) were randomly...[Objectives] To study the anti-inflammatory effects and its possible action mechanism of Pereskia aculeate Miller on rats with adjuvant arthritis( AJ). [Methods] Fifty SD rats( half male and half female) were randomly divided into 5 groups: blank group,model group,positive control group( Glucosidorum Tripterygll Totorum( GTT),12 mg/kg),and P. aculeate high and low dose group( 0. 86 and0. 43 g/m L). Except the blank group,other groups were induced with complete Freund's adjuvant( CFA) to establish the AA rat model. On the 17 th day of modeling,the drug was externally applied for soaking,and the diameter of foot hole and foot joint before and after administration was measured to observe the degree of swelling. The enzyme-linked immunosorbent assay( ELISA) was adopted to determine the inflammatory cytokines interleukin-1β( IL-1β) and tumor necrosis factor-α( TNF-α). [Results] Compared with the model group,the degree of swelling of the foot sole and foot joints was reduced in the P. aculeate high dose group and the positive control group( P < 0. 05). According to ELISA test,compared with the model control group,the serum levels of IL-1β( P < 0. 05) and TNF-α( P < 0. 05) were significantly reduced in the P. aculeate high dose group and the positive control group. Compared with the positive control group,there was no significant difference( P > 0. 05). [Conclusions] P. aculeate has significant inhibitory effects on foot swelling of adjuvant arthritis in rats,and the action mechanism is possibly related to the decrease of IL-1β and TNF-α.展开更多
Adverse drug reactions (ADRs) are an important clinical problem and contribute significantly to mortality and morbidity. Scant data on the safety of drug use in children are usually available at the time of marketing ...Adverse drug reactions (ADRs) are an important clinical problem and contribute significantly to mortality and morbidity. Scant data on the safety of drug use in children are usually available at the time of marketing authorization, due to the limited number of trials performed in the paediatric population. Few studies monitored the incidence of ADRs in Italian hospitalized children, that cannot be compared for methodological reasons. A 6-month prospective observational study was, therefore, conducted on the paediatric wards of five hospitals in the Campania Region, Italy. Data were collected on all patients admitted to the wards during the study period through a structured questionnaire administered to the mothers and through a hospital chart review. Of the 752 patients enrolled, 86.2% were exposed to one or more drugs during hospitalization. The therapeutic class most prescribed was systemic antibacterial agents (47%). Six ADRs occurred during hospitalization (incidence 0.9%;95% CI 0.2% - 1.7%). In addition, one child was admitted to a hospital for an ADR. Five out of seven ADRs occurred in girls. The skin was the most affected organ. The medications implicated were amoxicillin, acyclovir, ibuprofen, ceftriaxone, paracetamol, and ranitidine. According to the Naranjo probability criteria, six ADRs were probably, and one possibly, related to the suspected drug. In conclusion, this study reveals that ADRs may be under-reported in children hospitalized in the Campania Region. Consequently, healthcare personnel should be alert to the possibility of ADRs. More accurate reporting of ADRs in children would result in safer use of drugs in such patients.展开更多
Alcoholic liver disease(ALD) is the commonest cause of cirrhosis in many Western countries and it has a high rate of morbidity and mortality. The pathogenesis is characterized by complex interactions between metabolic...Alcoholic liver disease(ALD) is the commonest cause of cirrhosis in many Western countries and it has a high rate of morbidity and mortality. The pathogenesis is characterized by complex interactions between metabolic intermediates of alcohol. Bacterial intestinal flora is itself responsible for production of endogenous ethanol through the fermentation of carbohydrates. The intestinal metabolism of alcohol produces a high concentration of toxic acetaldehyde that modifies gut permeability and microbiota equilibrium. Furthermore it causes direct hepatocyte damage. In patients who consume alcohol over a long period, there is a modification of gut microbiota and, in particular, an increment of Gram negative bacteria. This causes endotoxemia and hyperactivation of the immune system. Endotoxin is a constituent of Gram negative bacteria cell walls. Two types of receptors, cluster of differentiation 14 and Toll-like receptors-4, present on Kupffer cells, recognize endotoxins. Several studies have demonstrated the importance of gut-liver axis and new treatments have been studied in recent years to reduce progression of ALD modifying gut microbiota. It has focused attention on antibiotics, prebiotics, probiotics and synbiotics.展开更多
The introduction of tacrolimus in clinical practice has improved patient survival after organ transplant.However,despite the long use of tacrolimus in clinical practice,the best way to use this agent is still a matter...The introduction of tacrolimus in clinical practice has improved patient survival after organ transplant.However,despite the long use of tacrolimus in clinical practice,the best way to use this agent is still a matter of intense debate.The start of the genomic era has generated new research areas,such as pharmacogenetics,which studies the variability of drug response in relation to the genetic factors involved in the processes responsible for the pharmacokinetics and/or the action mechanism of a drug in the body.This variability seems to be correlated with the presence of genetic polymorphisms.Genotyping is an attractive option especially for the initiation of the dosing of tacrolimus;also,unlike phenotypic tests,the genotype is a stable characteristic that needs to be determined only once for any given gene.However,prospective clinical studies must show that genotype determination before transplantation allows for better use of a given drug and improves the safety and clinical efficacy of that medication.At present,research has been able to reliably show that the CYP3A5 genotype,but not the CYP3A4 or ABCB1 ones,can modify the pharmacokinetics of tacrolimus.However,it has not been possible to incontrovertibly show that the corresponding changes in the pharmacokinetic profile are linked with different patient outcomes regarding tacrolimus efficacy and toxicity.For these reasons,pharmacogenetics and individualized medicine remain a fascinating area for further study and may ultimately become the face of future medical practice and drug dosing.展开更多
Aim： To investigate the influence of an extract obtained from five Chinese medicinal plants on sexual behavior of adult male rats. Methods： The extract was administered at doses of 30, 60 and 120 mg/kg by oral gavag...Aim： To investigate the influence of an extract obtained from five Chinese medicinal plants on sexual behavior of adult male rats. Methods： The extract was administered at doses of 30, 60 and 120 mg/kg by oral gavage, acutely （one time, 45 min before mating test） or subchronically （daily for 10 days） in sexually potent and sexually sluggish/impotent rats. Sexual behavior, serum levels of luteinizing hormone （LH） and testosterone （T） were evaluated in treated rats and compared with controls receiving vehicle. The effect of the extract on central dopaminergic neurotransmission was assessed in the nucleus accumbens using a microdialysis technique. Results： In sexually potent rats, both acute and subchronic treatment with the extract dosed at 30 and 60 mg/kg reduced mount latency and intromission latency. In sluggish/impotent rats, the acutely administered extract at the dose of 60 mg/kg shortened ejaculation latency, whereas subchronically administered at the doses of 30 and 60 mg/kg, reduced mount, intromission and ejaculation latencies, increasing also the percentage of mounting and ejaculating rats. The extract dosed at 60 mg/kg significantly increased LH and T following acute and subchronic administration and increased 3,4-dihydroxyphenylacetic acid levels in the nucleus accumbens, 30 min after the acute administration. Conclusion： The improvement in both appetitive and consummatory components of sexual behavior observed in male rats treated with the extract could be ascribed to increased serum T level in parallel with the activation of the central dopaminergic system.展开更多
The dopaminergic system controls several vital central nervous system functions, including the control of movement, reward behaviors and cognition. Alterations of dopaminergic signaling are involved in the pathogenesi...The dopaminergic system controls several vital central nervous system functions, including the control of movement, reward behaviors and cognition. Alterations of dopaminergic signaling are involved in the pathogenesis of neurodegenerative and psychiatric disorders, in particular Parkinson’s disease, which are associated with a subtle and chronic inflammatory response. A substantial body of evidence has demonstrated the non-neuronal expression of dopamine, its receptors and of the machinery that governs synthesis, secretion and storage of dopamine across several immune cell types. This review aims to summarize current knowledge on the role and expression of dopamine in immune cells. One of the goals is to decipher the complex mechanisms through which these cell types respond to dopamine, in order to address the impact this has on neurodegenerative and psychiatric pathologies such as Parkinson’s disease. A further aim is to illustrate the gaps in our understanding of the physiological roles of dopamine to encourage more targeted research focused on understanding the consequences of aberrant dopamine production on immune regulation. These highlights may prompt scientists in the field to consider alternative functions of this important neurotransmitter when targeting neuroinflammatory/neurodegenerative pathologies.展开更多
Depression refers to a series of mental health issues characterized by loss of interest and enjoyment in everyday life,low mood and selected emotional,cognitive,physical and behavioral symptoms.Depression is a common ...Depression refers to a series of mental health issues characterized by loss of interest and enjoyment in everyday life,low mood and selected emotional,cognitive,physical and behavioral symptoms.Depression is a common disorder,affecting 5–15%of the general population.When diagnosed as major depressive disorder（MDD）,patients are currentlytreated with pharmacological agents such as serotonin or noradren- aline uptake inhibitors （SSRI or SNRI） or tricyclics.展开更多
AIM:To evaluate the serum levels of endozepine-4,their relation with ammonia serum levels,the grading of coma and the severity of cirrhosis,in patients with hepatic coma. METHODS:In this study we included 20 subjects ...AIM:To evaluate the serum levels of endozepine-4,their relation with ammonia serum levels,the grading of coma and the severity of cirrhosis,in patients with hepatic coma. METHODS:In this study we included 20 subjects with Hepatic coma,20 subjects with minimal hepatic encephalopathy(MHE) and 20 subjects control. All subjects underwent blood analysis,Child Pugh and Model for End- stage liver disease(MELD) assessment,endozepine-4 analysis. RESULTS:Subjects with hepatic coma showed significant difference in endozepine-4(P < 0.001) and NH3 levels(P < 0.001) compared both to MHE and controls patients. Between NH3 and endozepine-4 we observed a significant correlation(P = 0.009; Pearson correlation 0.570). There was a significant correlation between endozepine-4 and MELD(P = 0.017; Pearsoncorrelation = 0.529). In our study blood ammonia concentration was noted to be raised in patients with hepatic coma,with the highest ammonia levels being found in those who were comatose. We also found a high correlation between endozepine-4 and ammonia(P < 0.001). In patients with grade Ⅳ hepatic coma,endozepine levels were significantly higher compared to other groups. CONCLUSION:This study suggests that an increased level of endozepine in subjects with higher levels of MELD was observed. In conclusion,data concerning involvement of the GABA-ergic system in HE coma could be explained by stage-specific alterations.展开更多
Major depressive disorder(MDD)is a common psychiatric condition characterized by two main symptoms,low mood and anhedonia.About 15–30%of people suffering from MDD do not respond to standard-of-care antidepressants,e....Major depressive disorder(MDD)is a common psychiatric condition characterized by two main symptoms,low mood and anhedonia.About 15–30%of people suffering from MDD do not respond to standard-of-care antidepressants,e.g.,the serotonin re-uptake inhibitors(SSRI),and are considered affected by Treatment-Resistant Depression(TRD).The neurobiology of this condition is presently unknown.Recent attempts of developing novel treatments for TRD have been driven by four major breakthroughs:(1)Increasing dopaminergic neurotransmission improves TRD symptoms;(2)Anhedonia occurs when central dopaminergic neurotransmission is low;(3)Enhanced neuroplasticity is critical for the action of antidepressants;(4)Ketamine shows antidepressant properties in TRD patients and triggers neuroplasticity in preclinical animal models.These breakthroughs are at the basis of a putative human translational cellular model for antidepressant agents that we are proposing in this article.The rationale is briefly described here.展开更多
Dipeptidyl peptidase IV （DPP-IV） is a serine protease best known for its role in inactivating glucagon-like peptide-1 （GLP-1）, pituitary adenylate cyclase-activating polypeptide （PACAP） and glucose-dependent ins...Dipeptidyl peptidase IV （DPP-IV） is a serine protease best known for its role in inactivating glucagon-like peptide-1 （GLP-1）, pituitary adenylate cyclase-activating polypeptide （PACAP） and glucose-dependent insulinotropic peptide （GIP）, three stimulators of pancreatic insulin secretion with beneficial effects on glucose disposal. Owing to the relationship between DPP-IV and these peptides, inhibition of DPP-IV enzyme activity is considered as an attractive treatment option for diabetic patients. Nonetheless, increasing studies support the idea that DPP-IV might also be involved in the development of neurological disorders with a neuroinflammatory component, potentially through its non-incretin activities on immune cells. In this review article, we aim at highlighting recent literature describing the therapeutic value of DPP-IV inhibitors for the treatment of such neurological conditions. Finally, we will illustrate some of the promising results obtained using berberine, a plant extract with potent inhibitory activity on DPP-IV.展开更多
Aims: To determine in a case-control study possible associations between the development of acute renal failure in preterm newborns and therapeutic interventions, particularly drug treatments. Methods: The study popul...Aims: To determine in a case-control study possible associations between the development of acute renal failure in preterm newborns and therapeutic interventions, particularly drug treatments. Methods: The study population was 172 preterm infants of < 38 weeks gestation; 71 had acute renal failure and 101 were controls closely matched for gestational age and birth weight. Maternal and neonatal information was collected for both groups through questionnaires and interviews. Routine data on renal variables were also collected. Univariate and multivariate logistic regression analyses were performed. Results: Very low birthweight infants were at high risk of acute renal failure (79% of cases were < 1500 g). However, the acute renal failure was transient. Mothers of infants with acute renal failure received more drugs during pregnancy and delivery (mainly antibiotics and non-steroidal anti-inflammatory drugs). Of the possible therapeutic interventions, intubation, catheterisation, and phototherapy were mainly applied to case subjects. A low Apgar score and patent ductus arteriosus were diagnosed in a greater percentage of neonates with acute renal failure. Moreover, in the first few days of life and before diagnosis of acute renal failure, case subjects received more drugs (antibiotics, non-steroidal anti-inflammatory drugs, and diuretics) and for a longer time. In the multivariate logistic analysis, medullary hyperechogenicity (odds ratio (OR) 4.491; 95% confidence interval (Cl) 1.879 to 10.731) and ceftazidime administration (OR 5.082; 95% Cl 1.493 to 17.297) were associated with a greater risk of acute renal failure. Conclusions: The results suggest the need for careful monitoring of very low birthweight infants and attention to drug treatments, as it is difficult to differentiate between normality and renal failure in the first few days of life.展开更多
文摘It is our contention that the concept of a probiotic as a living bacterium providing unspecified health benefits is inhibiting the development and establishment of an evidence base for the growing field of pharmacobiotics.We believe this is due in part to the current regulatory framework,lack of a clear definition of a probiotic,the ease with which currently defined probiotics can be positioned in the market place,and the enormous profits earned for minimum investment in research.To avoid this,we believe the following two actions are mandatory:international guidelines by a forum of stakeholders made available to scientists and clinicians,patient organizations,and governments;public research funds made available to the scientific community for performing independent rigorous studies both at the preclinical and clinical levels.
基金the National Foundation for Science & Technology Development(NAFOSTED) of Vietnam for financial support of this research(code:104.01-2013.62)the Italian Ministery of Foreign Affairs and International Cooperation(MAECI)
文摘Objective:To investigate the anti-proliferative effects of 20-hydroxyecdysone isolated from the bark of Dacrycarpus imbricatus(Blume) de Laub.Methods:Column chromatography was used for isolation of compounds from plant material.The structure of the isolated compound was identified by mass spectrometry and nuclear magnetic resonance techniques,including HSQC,HMBC,NOE-difference experiments.The isolated compound was tested for its anti-proliferative activity in acute myeloid leukemia(AML) and OCI-AML cells.Results:Compound 1 was isolated from the ethyl acetate fraction of Dacrycarpus imbricatus barks by column chromatography.Its chemical structure was identified as 20-hydroxyecdysone(20HE),a cholestane-type ecdysteroid,by a combination of mass spectrometry and nuclear magnetic resonance spectrometric analyses.Our goal was to test the anti-proliferative activity of 20 HE using the OCI-AML cell line.20 HE significantly decreased OCI cell number at a concentration of 1 mg/mL,whereas lower concentrations were ineffective.Moreover,this decrease was due to partial blockage of the G_1/S phase of the cell cycle,with a reduction of cells in the G_2M phase,not due to increased apoptosis.Conclusions:This indicates that 20 HE significantly decreases the number of cells in the G_1/S phase of the cell cycle in human AML cells.This is the first time that the anti-proliferative activity of 20 HE against a human tumor cell line has been reported.
基金Supported by Natural Science Foundation Project of Guangxi(2017GXNSF AA198255)Young Scholar Project of Natural Science Foundation of Guangxi University of Chinese Medicine(2015LX037)Student's Platform for Innovation and Entrepreneurship Training Program of Guangxi Zhuang Autonomous Region,China in 2016(201610601016)
文摘[Objectives] To study the anti-inflammatory effects and its possible action mechanism of Pereskia aculeate Miller on rats with adjuvant arthritis( AJ). [Methods] Fifty SD rats( half male and half female) were randomly divided into 5 groups: blank group,model group,positive control group( Glucosidorum Tripterygll Totorum( GTT),12 mg/kg),and P. aculeate high and low dose group( 0. 86 and0. 43 g/m L). Except the blank group,other groups were induced with complete Freund's adjuvant( CFA) to establish the AA rat model. On the 17 th day of modeling,the drug was externally applied for soaking,and the diameter of foot hole and foot joint before and after administration was measured to observe the degree of swelling. The enzyme-linked immunosorbent assay( ELISA) was adopted to determine the inflammatory cytokines interleukin-1β( IL-1β) and tumor necrosis factor-α( TNF-α). [Results] Compared with the model group,the degree of swelling of the foot sole and foot joints was reduced in the P. aculeate high dose group and the positive control group( P < 0. 05). According to ELISA test,compared with the model control group,the serum levels of IL-1β( P < 0. 05) and TNF-α( P < 0. 05) were significantly reduced in the P. aculeate high dose group and the positive control group. Compared with the positive control group,there was no significant difference( P > 0. 05). [Conclusions] P. aculeate has significant inhibitory effects on foot swelling of adjuvant arthritis in rats,and the action mechanism is possibly related to the decrease of IL-1β and TNF-α.
文摘Adverse drug reactions (ADRs) are an important clinical problem and contribute significantly to mortality and morbidity. Scant data on the safety of drug use in children are usually available at the time of marketing authorization, due to the limited number of trials performed in the paediatric population. Few studies monitored the incidence of ADRs in Italian hospitalized children, that cannot be compared for methodological reasons. A 6-month prospective observational study was, therefore, conducted on the paediatric wards of five hospitals in the Campania Region, Italy. Data were collected on all patients admitted to the wards during the study period through a structured questionnaire administered to the mothers and through a hospital chart review. Of the 752 patients enrolled, 86.2% were exposed to one or more drugs during hospitalization. The therapeutic class most prescribed was systemic antibacterial agents (47%). Six ADRs occurred during hospitalization (incidence 0.9%;95% CI 0.2% - 1.7%). In addition, one child was admitted to a hospital for an ADR. Five out of seven ADRs occurred in girls. The skin was the most affected organ. The medications implicated were amoxicillin, acyclovir, ibuprofen, ceftriaxone, paracetamol, and ranitidine. According to the Naranjo probability criteria, six ADRs were probably, and one possibly, related to the suspected drug. In conclusion, this study reveals that ADRs may be under-reported in children hospitalized in the Campania Region. Consequently, healthcare personnel should be alert to the possibility of ADRs. More accurate reporting of ADRs in children would result in safer use of drugs in such patients.
文摘Alcoholic liver disease(ALD) is the commonest cause of cirrhosis in many Western countries and it has a high rate of morbidity and mortality. The pathogenesis is characterized by complex interactions between metabolic intermediates of alcohol. Bacterial intestinal flora is itself responsible for production of endogenous ethanol through the fermentation of carbohydrates. The intestinal metabolism of alcohol produces a high concentration of toxic acetaldehyde that modifies gut permeability and microbiota equilibrium. Furthermore it causes direct hepatocyte damage. In patients who consume alcohol over a long period, there is a modification of gut microbiota and, in particular, an increment of Gram negative bacteria. This causes endotoxemia and hyperactivation of the immune system. Endotoxin is a constituent of Gram negative bacteria cell walls. Two types of receptors, cluster of differentiation 14 and Toll-like receptors-4, present on Kupffer cells, recognize endotoxins. Several studies have demonstrated the importance of gut-liver axis and new treatments have been studied in recent years to reduce progression of ALD modifying gut microbiota. It has focused attention on antibiotics, prebiotics, probiotics and synbiotics.
文摘The introduction of tacrolimus in clinical practice has improved patient survival after organ transplant.However,despite the long use of tacrolimus in clinical practice,the best way to use this agent is still a matter of intense debate.The start of the genomic era has generated new research areas,such as pharmacogenetics,which studies the variability of drug response in relation to the genetic factors involved in the processes responsible for the pharmacokinetics and/or the action mechanism of a drug in the body.This variability seems to be correlated with the presence of genetic polymorphisms.Genotyping is an attractive option especially for the initiation of the dosing of tacrolimus;also,unlike phenotypic tests,the genotype is a stable characteristic that needs to be determined only once for any given gene.However,prospective clinical studies must show that genotype determination before transplantation allows for better use of a given drug and improves the safety and clinical efficacy of that medication.At present,research has been able to reliably show that the CYP3A5 genotype,but not the CYP3A4 or ABCB1 ones,can modify the pharmacokinetics of tacrolimus.However,it has not been possible to incontrovertibly show that the corresponding changes in the pharmacokinetic profile are linked with different patient outcomes regarding tacrolimus efficacy and toxicity.For these reasons,pharmacogenetics and individualized medicine remain a fascinating area for further study and may ultimately become the face of future medical practice and drug dosing.
文摘Aim： To investigate the influence of an extract obtained from five Chinese medicinal plants on sexual behavior of adult male rats. Methods： The extract was administered at doses of 30, 60 and 120 mg/kg by oral gavage, acutely （one time, 45 min before mating test） or subchronically （daily for 10 days） in sexually potent and sexually sluggish/impotent rats. Sexual behavior, serum levels of luteinizing hormone （LH） and testosterone （T） were evaluated in treated rats and compared with controls receiving vehicle. The effect of the extract on central dopaminergic neurotransmission was assessed in the nucleus accumbens using a microdialysis technique. Results： In sexually potent rats, both acute and subchronic treatment with the extract dosed at 30 and 60 mg/kg reduced mount latency and intromission latency. In sluggish/impotent rats, the acutely administered extract at the dose of 60 mg/kg shortened ejaculation latency, whereas subchronically administered at the doses of 30 and 60 mg/kg, reduced mount, intromission and ejaculation latencies, increasing also the percentage of mounting and ejaculating rats. The extract dosed at 60 mg/kg significantly increased LH and T following acute and subchronic administration and increased 3,4-dihydroxyphenylacetic acid levels in the nucleus accumbens, 30 min after the acute administration. Conclusion： The improvement in both appetitive and consummatory components of sexual behavior observed in male rats treated with the extract could be ascribed to increased serum T level in parallel with the activation of the central dopaminergic system.
基金supported by a Research Development Fund(UTS Start-Up Grant 2018)from the University of Technology Sydney to AC。
文摘The dopaminergic system controls several vital central nervous system functions, including the control of movement, reward behaviors and cognition. Alterations of dopaminergic signaling are involved in the pathogenesis of neurodegenerative and psychiatric disorders, in particular Parkinson’s disease, which are associated with a subtle and chronic inflammatory response. A substantial body of evidence has demonstrated the non-neuronal expression of dopamine, its receptors and of the machinery that governs synthesis, secretion and storage of dopamine across several immune cell types. This review aims to summarize current knowledge on the role and expression of dopamine in immune cells. One of the goals is to decipher the complex mechanisms through which these cell types respond to dopamine, in order to address the impact this has on neurodegenerative and psychiatric pathologies such as Parkinson’s disease. A further aim is to illustrate the gaps in our understanding of the physiological roles of dopamine to encourage more targeted research focused on understanding the consequences of aberrant dopamine production on immune regulation. These highlights may prompt scientists in the field to consider alternative functions of this important neurotransmitter when targeting neuroinflammatory/neurodegenerative pathologies.
基金funded by Ministry of Education,University and Research(MIUR)ex-60% research fund University of Brescia,Italy
文摘Depression refers to a series of mental health issues characterized by loss of interest and enjoyment in everyday life,low mood and selected emotional,cognitive,physical and behavioral symptoms.Depression is a common disorder,affecting 5–15%of the general population.When diagnosed as major depressive disorder（MDD）,patients are currentlytreated with pharmacological agents such as serotonin or noradren- aline uptake inhibitors （SSRI or SNRI） or tricyclics.
文摘AIM:To evaluate the serum levels of endozepine-4,their relation with ammonia serum levels,the grading of coma and the severity of cirrhosis,in patients with hepatic coma. METHODS:In this study we included 20 subjects with Hepatic coma,20 subjects with minimal hepatic encephalopathy(MHE) and 20 subjects control. All subjects underwent blood analysis,Child Pugh and Model for End- stage liver disease(MELD) assessment,endozepine-4 analysis. RESULTS:Subjects with hepatic coma showed significant difference in endozepine-4(P < 0.001) and NH3 levels(P < 0.001) compared both to MHE and controls patients. Between NH3 and endozepine-4 we observed a significant correlation(P = 0.009; Pearson correlation 0.570). There was a significant correlation between endozepine-4 and MELD(P = 0.017; Pearsoncorrelation = 0.529). In our study blood ammonia concentration was noted to be raised in patients with hepatic coma,with the highest ammonia levels being found in those who were comatose. We also found a high correlation between endozepine-4 and ammonia(P < 0.001). In patients with grade Ⅳ hepatic coma,endozepine levels were significantly higher compared to other groups. CONCLUSION:This study suggests that an increased level of endozepine in subjects with higher levels of MELD was observed. In conclusion,data concerning involvement of the GABA-ergic system in HE coma could be explained by stage-specific alterations.
基金funded by Ministry of Education,University and Research(MIUR)ex-60%research fund University of Brescia,Italy.Emilio Merlo Pich is employee of Takeda Pharmaceutical International AG
文摘Major depressive disorder(MDD)is a common psychiatric condition characterized by two main symptoms,low mood and anhedonia.About 15–30%of people suffering from MDD do not respond to standard-of-care antidepressants,e.g.,the serotonin re-uptake inhibitors(SSRI),and are considered affected by Treatment-Resistant Depression(TRD).The neurobiology of this condition is presently unknown.Recent attempts of developing novel treatments for TRD have been driven by four major breakthroughs:(1)Increasing dopaminergic neurotransmission improves TRD symptoms;(2)Anhedonia occurs when central dopaminergic neurotransmission is low;(3)Enhanced neuroplasticity is critical for the action of antidepressants;(4)Ketamine shows antidepressant properties in TRD patients and triggers neuroplasticity in preclinical animal models.These breakthroughs are at the basis of a putative human translational cellular model for antidepressant agents that we are proposing in this article.The rationale is briefly described here.
文摘Dipeptidyl peptidase IV （DPP-IV） is a serine protease best known for its role in inactivating glucagon-like peptide-1 （GLP-1）, pituitary adenylate cyclase-activating polypeptide （PACAP） and glucose-dependent insulinotropic peptide （GIP）, three stimulators of pancreatic insulin secretion with beneficial effects on glucose disposal. Owing to the relationship between DPP-IV and these peptides, inhibition of DPP-IV enzyme activity is considered as an attractive treatment option for diabetic patients. Nonetheless, increasing studies support the idea that DPP-IV might also be involved in the development of neurological disorders with a neuroinflammatory component, potentially through its non-incretin activities on immune cells. In this review article, we aim at highlighting recent literature describing the therapeutic value of DPP-IV inhibitors for the treatment of such neurological conditions. Finally, we will illustrate some of the promising results obtained using berberine, a plant extract with potent inhibitory activity on DPP-IV.
文摘Aims: To determine in a case-control study possible associations between the development of acute renal failure in preterm newborns and therapeutic interventions, particularly drug treatments. Methods: The study population was 172 preterm infants of < 38 weeks gestation; 71 had acute renal failure and 101 were controls closely matched for gestational age and birth weight. Maternal and neonatal information was collected for both groups through questionnaires and interviews. Routine data on renal variables were also collected. Univariate and multivariate logistic regression analyses were performed. Results: Very low birthweight infants were at high risk of acute renal failure (79% of cases were < 1500 g). However, the acute renal failure was transient. Mothers of infants with acute renal failure received more drugs during pregnancy and delivery (mainly antibiotics and non-steroidal anti-inflammatory drugs). Of the possible therapeutic interventions, intubation, catheterisation, and phototherapy were mainly applied to case subjects. A low Apgar score and patent ductus arteriosus were diagnosed in a greater percentage of neonates with acute renal failure. Moreover, in the first few days of life and before diagnosis of acute renal failure, case subjects received more drugs (antibiotics, non-steroidal anti-inflammatory drugs, and diuretics) and for a longer time. In the multivariate logistic analysis, medullary hyperechogenicity (odds ratio (OR) 4.491; 95% confidence interval (Cl) 1.879 to 10.731) and ceftazidime administration (OR 5.082; 95% Cl 1.493 to 17.297) were associated with a greater risk of acute renal failure. Conclusions: The results suggest the need for careful monitoring of very low birthweight infants and attention to drug treatments, as it is difficult to differentiate between normality and renal failure in the first few days of life.
