ABSTRACT
AIM: Glutamatergic neurotransmission in the nucleus accumbens (NAc) is crucial for the relapse to heroin seeking. The aim of this study was to determine whether mGluR5 in the NAc core or shell involved in heroin seeking behavior in rats. METHODS: Male SD rats were self-administered heroin under a fixed-ratio 1 (FR1) reinforcement schedule for 14 d, and subsequently withdrawn for 2 weeks. The selective mGluR5 antagonist 2-methyl-6-phenylethynyl-pyridine (MPEP, 5, 15 and 50 nmol per side) was then microinjected into the NAc core or shell 10 min before a heroin-seeking test induced by context, cues or heroin priming. RESULTS: Microinjection of MPEP into the NAc shell dose-dependently decreased the heroin seeking induced by context, cues or heroin priming. In contrast, microinjection of MPEP into the NAc core did not alter the heroin seeking induced by cues or heroin priming. In addition, microinjection with MPEP (15 nmol per side) in the NAc shell reversed both the percentage of open arms entries (OE%) and the percentage of time spent in open arms (OT%) after heroin withdrawal. Microinjection of MPEP (50 nmol per side) in the striatum as a control location did not affect the heroin seeking behavior. Microinjection of MPEP in the 3 locations did not change the locomotion activities. CONCLUSION: Blockade of mGluR5 in NAc shell in rats specifically suppresses the relapse to heroin-seeking and anxiety-like behavior, suggesting that mGluR5 antagonists may be a potential candidate for the therapy of heroin addiction.
Subject(s)
Analgesics, Opioid/administration & dosage , Behavior, Animal/drug effects , Drug-Seeking Behavior/drug effects , Excitatory Amino Acid Antagonists/pharmacology , Heroin Dependence/drug therapy , Heroin/administration & dosage , Nucleus Accumbens/drug effects , Pyridines/pharmacology , Receptor, Metabotropic Glutamate 5/antagonists & inhibitors , Animals , Anxiety/drug therapy , Anxiety/metabolism , Anxiety/psychology , Cues , Dose-Response Relationship, Drug , Excitatory Amino Acid Antagonists/administration & dosage , Heroin Dependence/metabolism , Heroin Dependence/psychology , Locomotion/drug effects , Male , Nucleus Accumbens/metabolism , Pyridines/administration & dosage , Rats, Sprague-Dawley , Receptor, Metabotropic Glutamate 5/metabolism , Recurrence , Self Administration , Substance Withdrawal Syndrome/drug therapy , Substance Withdrawal Syndrome/metabolism , Substance Withdrawal Syndrome/psychology , Time FactorsABSTRACT
OBJECTIVES: Long-term use of methamphetamine (MA) induces the neuron damage and leads to multiple neuropsychiatric disorders. However, the effect of MA on the female reproductive functions has not yet been evaluated. The objective of this study was to determine the prevalence of abnormal menstrual cycling in female MA users. METHODS: Female MA users (N = 113) were recruited from the Zhangjiang Isolated Compulsory Detoxification Center. Gynecologic history and drug use history were recorded, and serum levels of follicle-stimulating hormone, luteinizing hormone, prolactin, estrogen, progesterone, and testosterone were measured. RESULTS: Long-term use of MA significantly altered the menstrual cycle, and 33.6% women suffered from abnormal uterine bleeding while using MA. Deregulation of sex hormones was observed in 73.3% of participants during abstinence. The most common patterns were simple anovular menstruation, which was caused mainly by a hypothalamic deregulation and pituitary suppression with or without ovarian suppression. Normal hormone levels were observed more frequently in participants abstinent for more than 10 months (39.5%) than in participants who were abstinent for less than 10 months (18.6%). However, no relationship was found between hormone deregulation and age or history of MA use. CONCLUSIONS: The present data demonstrate that long-term use of MA results in the disruption of menstrual cycles and dysfunction of hypothalamic-pituitary-gonadal axis in women.
Subject(s)
Amphetamine-Related Disorders/complications , Central Nervous System Stimulants/adverse effects , Hypothalamo-Hypophyseal System/drug effects , Menstrual Cycle/drug effects , Methamphetamine/adverse effects , Ovary/drug effects , Adult , Amphetamine-Related Disorders/blood , Amphetamine-Related Disorders/physiopathology , Estrogens/blood , Female , Follicle Stimulating Hormone/blood , Humans , Hypothalamo-Hypophyseal System/physiopathology , Luteinizing Hormone/blood , Menstruation Disturbances/blood , Menstruation Disturbances/chemically induced , Menstruation Disturbances/physiopathology , Ovary/physiopathology , Progesterone/blood , Prolactin/blood , Testosterone/blood , Young AdultABSTRACT
We recently found that moderate consumption of two unrelated red wines generate from different grape species, a Cabernet Sauvignon and a muscadine wine that are characterized by distinct component composition of polyphenolic compounds, significantly attenuated the development of Alzheimer's disease (AD)-type brain pathology and memory deterioration in a transgenic AD mouse model. Interestingly, our evidence suggests that the two red wines attenuated AD phenotypes through independent mechanisms. In particular, we previously found that treatment with Cabernet Sauvignon reduced the generation of AD-type amyloid-beta (Abeta) peptides. In contrast, evidence from our present study suggests that muscadine treatment attenuates Abeta neuropathology and Abeta-related cognitive deterioration in Tg2576 mice by interfering with the oligomerization of Abeta molecules to soluble high-molecular-weight Abeta oligomer species that are responsible for initiating a cascade of cellular events resulting in cognitive decline. Collectively, our observations suggest that distinct polyphenolic compounds from red wines may be bioavailable at the organism level and beneficially modulate AD phenotypes through multiple Abeta-related mechanisms. Results from these studies suggest the possibility of developing a "combination" of dietary polyphenolic compounds for AD prevention and/or therapy by modulating multiple Abeta-related mechanisms.
Subject(s)
Alzheimer Disease/pathology , Alzheimer Disease/prevention & control , Cognition Disorders/pathology , Cognition Disorders/prevention & control , Flavonoids/chemistry , Flavonoids/pharmacology , Phenols/chemistry , Phenols/pharmacology , Wine/analysis , Amyloid Precursor Protein Secretases/metabolism , Animals , Behavior, Animal/drug effects , Cross-Linking Reagents , Electrophoresis, Polyacrylamide Gel , Female , Flavonoids/toxicity , Maze Learning/drug effects , Mice , Mice, Transgenic , Molecular Weight , Phenols/toxicity , Plaque, Amyloid/drug effects , Plaque, Amyloid/pathology , Polyphenols , Space Perception/drug effects , Wine/toxicityABSTRACT
AIMS: The fragile histidine triad (FHIT) gene is frequently inactivated in human cancers; however, the FHIT gene remains unexplored in Hodgkin's lymphoma. The aim of this study was to investigate the role of FHIT expression in classical Hodgkin's lymphoma. METHODS: Classical Hodgkin's lymphomas were analysed for FHIT gene expression by two-step non-biotin immunohistochemical method and Western blotting. RESULTS: Thirty of the 33 (91%) cases of Hodgkin's lymphoma tested were positive for FHIT protein by immuohistochemistry. The expression of FHIT was mainly located in cytoplasm of Reed-Sternberg (HRS) cells. The protein expression was also documented by Western blotting. The non-Hodgkin's lymphomas were negative for FHIT protein. CONCLUSIONS: The results indicate that abnormal FHIT expression is noted frequently in classical Hodgkin's lymphoma and the expression can give insight into the pathogenesis of the disease. The protein may serve as a marker to localise HRS cells in classical Hodgkin's lymphoma.
Subject(s)
Acid Anhydride Hydrolases/metabolism , Biomarkers, Tumor/metabolism , Genes, Tumor Suppressor , Hodgkin Disease/metabolism , Neoplasm Proteins/metabolism , Acid Anhydride Hydrolases/genetics , Biomarkers, Tumor/genetics , Blotting, Western , Female , Gene Expression , Hodgkin Disease/genetics , Hodgkin Disease/pathology , Humans , Immunoenzyme Techniques , Male , Neoplasm Proteins/genetics , Reed-Sternberg Cells/metabolism , Reed-Sternberg Cells/pathologyABSTRACT
OBJECTIVE: To study the expression of FHIT protein and its potential application in diagnosing classic Hodgkin lymphoma. METHODS: Immunohistochemical study using EnVision method for FHIT tumor suppressor protein, hematopoietic stem cell markers CD133/AC133 and CD34, B-cell marker CD20, T-cell marker CD3 and oncoprotein c-erbB2 was performed on 33 cases of classic Hodgkin lymphoma. RESULTS: Thirty-three of the Hodgkin lymphoma cases (90.9%) expressed FHIT protein. The antigen was mainly located in the cytoplasm, nucleus and membrane of classic Reed-Sternberg and Reed-Sternberg-like cells. Normal B and T lymphocytes, as well as their malignant counterparts, were negative for FHIT protein; whereas monocytes, histiocytes and dendritic cells were positive. All the cases studied were negative for CD133/AC133, CD34, CD3 and c-erbB-2. Two of the 33 cases showed positive staining for CD20 in some of the Reed-Sternberg cells. CONCLUSION: The expression of FHIT protein can be used as a useful adjunct in diagnosing classic Hodgkin lymphoma.
Subject(s)
Acid Anhydride Hydrolases/metabolism , Biomarkers, Tumor/metabolism , Hodgkin Disease/diagnosis , Neoplasm Proteins/metabolism , AC133 Antigen , Adolescent , Adult , Aged , Aged, 80 and over , Antigens, CD/metabolism , Antigens, CD20/metabolism , Cell Nucleus/metabolism , Child , Child, Preschool , Cytoplasm/metabolism , Female , Glycoproteins/metabolism , Hodgkin Disease/metabolism , Humans , Immunohistochemistry , Male , Middle Aged , Peptides/metabolism , Reed-Sternberg Cells/metabolism , Sensitivity and SpecificityABSTRACT
BACKGROUND: Hilar cholangiocarcinoma is associated with low resectability and poor survival. The aim of this study was to evaluate the roles of matrix metalloproteinases-2 (MMP-2) and its tissue inhibitor of metalloproteinase-2(TIMP-2) in tumor invasion or as a prognostic factor in patients with human hilar cholangiocarcinoma. METHODS: The expressions of MMP-2 and TIMP-2 were investigated in patients. Paraffinized tissue sections obtained from 50 patients with human hilar cholangiocarcinoma were analysed. The expressions of MMP-2 and TIMP-2 were examined immunohistochemically. Image analysis with image-pro plus analysis software was used to semiquantitatively determine the ratio of MMP-2 to TIMP-2. RESULTS: The expression levels of MMP-2 and TIMP-2 were strongly associated with tumor hepatic invasion in patients with hilar cholangiocarcinoma. Significant differences in the ratio of MMP-2 to TIMP-2 between some pathologic factors were observed in patients with hilar cholangiocarcinoma. CONCLUSIONS: MMP-2 plays an essential role in tumor invasion and metastasis, while TIMP-2 is shown to strongly inhibit cancer invasion and metastasis. The ratio of MMP-2 to TIMP-2 may be a prognostic indicator for patients with hilar cholangiocarcinoma.
