No abstract available.
Adamantane ; Humans ; Nitriles ; Pyrrolidines

OBJECTIVES: To examine emotional and psychological characteristics associated with suicide attempts in depressed patients. METHODS: A sample of 37 inpatients diagnosed with major depressive disorder or depressive disorder NOS was divided into two groups : lifetime suicide attempters(N=15 ; 40.54%), non-attempters(N=22 ; 59.46%). Beck Depression Scale(BDI), Beck Anxiety Scale(BAI), Hamilton Depression Rating Scale(HDRS), Hamilton Anxiety Rating Scale(HARS), and MMPI-2 were used to evaluate symptoms severity and psychological characteristics. RESULTS: Suicide attempters scored higher on the BDI though there were no group differences on the HDRS and on the both anxiety scales. Also they showed higher scores on the F, Fb, Pa, RC1, DEP, HEA, PK, AAS among MMPI-2 subscales. Our findings suggest that suicide attempters among depressed patients undergo more severe subjective distress and difficulties in adjustment than non-attempters. Also they were more hostile to others and showed lower trust. Lastly, they showed more somatic complaints and substance related problems. CONCLUSION: The present study showed that suicide attempters among depressed patients have distinct emotional and psychological characteristics. MMPI-2 would be helpful to assess suicidal risk of depressed patients.
Anxiety ; Depression ; Depressive Disorder ; Depressive Disorder, Major ; Humans ; Inpatients ; Pyrrolidines ; Suicide ; Weights and Measures

BACKGROUND: The aims of this study are to investigate the glycemic efficacy and predictive parameters of vildagliptin therapy in Korean subjects with type 2 diabetes. METHODS: In this retrospective study, we retrieved data for subjects who were on twice-daily 50 mg vildagliptin for at least 6 months, and classified the subjects into five treatment groups. In three of the groups, we added vildagliptin to their existing medication regimen; in the other two groups, we replaced one of their existing medications with vildagliptin. We then analyzed the changes in glucose parameters and clinical characteristics. RESULTS: Ultimately, 327 subjects were analyzed in this study. Vildagliptin significantly improved hemoglobin A1c (HbA1c) levels over 6 months. The changes in HbA1c levels (DeltaHbA1c) at month 6 were -2.24% (P=0.000), -0.77% (P=0.000), -0.80% (P=0.001), -0.61% (P=0.000), and -0.34% (P=0.025) for groups 1, 2, 3, 4, and 5, respectively, with significance. We also found significant decrements in fasting plasma glucose levels in groups 1, 2, 3, and 4 (P<0.05). Of the variables, initial HbA1c levels (P=0.032) and history of sulfonylurea use (P=0.026) were independently associated with responsiveness to vildagliptin treatment. CONCLUSION: Vildagliptin was effective when it was used in subjects with poor glycemic control. It controlled fasting plasma glucose levels as well as sulfonylurea treatment in Korean type 2 diabetic subjects.
Adamantane ; Diabetes Mellitus ; Dipeptidyl Peptidase 4 ; Fasting ; Glucose ; Hemoglobins ; Nitriles ; Plasma ; Pyrrolidines ; Retrospective Studies

Zinc released from excited glutamatergic neurons accelerates amyloid beta (A beta) aggregation, underscoring the therapeutic potential of zinc chelation for the treatment of Alzheimer's disease (AD). Zinc can also alter A beta concentration by affecting its degradation. In order to elucidate the possible role of zinc influx in secretase-processed A beta production, SH-SY5Y cells stably expressing amyloid precursor protein (APP) were treated with pyrrolidine dithiocarbamate (PDTC), a zinc ionophore, and the resultant changes in APP processing were examined. PDTC decreased A beta40 and A beta42 concentrations in culture media bathing APP-expressing SH-SY5Y cells. Measuring the levels of a series of C-terminal APP fragments generated by enzymatic cutting at different APP-cleavage sites showed that both beta- and alpha-cleavage of APP were inhibited by zinc influx. PDTC also interfered with the maturation of APP. PDTC, however, paradoxically increased the intracellular levels of A beta40. These results indicate that inhibition of secretase-mediated APP cleavage accounts -at least in part- for zinc inhibition of A beta secretion.
Alzheimer Disease ; Amyloid ; Baths ; Culture Media ; Neurons ; Proline ; Pyrrolidines ; Thiocarbamates ; Zinc

The purpose of this investigation was to re-evaluate the neurotrophic effect of GPI-1046 on neurite outgrowth in vitro. GPI-1046 was synthesized and identified with mass spectrometry, nuclear magnetic resonance and elemental analysis. Chicken dorsal root ganglions (DRGs) were removed and divided into three groups: (1) The DRGs were cultured in DMEM containing different concentrations of GPI-1046; (2) The DRGs were cultured in DMEM containing nerve growth factor (NGF) alone at 0.8 and 8 ng/mL, respectively; (3) The DRGs were cultured in DMEM containing both different concentrations of GPI-1046 and NGF at 0.8 ng/mL. The results showed that GPI-1046 alone could not stimulate chicken DRG neurite outgrowth; however, GPI-1046 stimulated DRG neurite outgrowth only in the presence of NGF at low concentration in the culture medium.
Animals ; Cells, Cultured ; Chickens ; Ganglia, Spinal ; drug effects ; growth & development ; Nerve Growth Factor ; pharmacology ; Neurites ; drug effects ; Pyrrolidines ; pharmacology

To study the application characteristics of copovidone (PVP-S630) in Xinyueshu extracts during the spray drying process, and its effect on such pharmaceutical properties as micromeritics and drug release behavior. PVP-S630 was added into Xinyueshu extracts to study on the spray drying, the effect of different dosages of PVP-S630 against the wall sticking effect of the spray drying, as well as the power property of Xinyueshu spray drying power and the dissolution in vitro behavior of the effective component of hyperoside. The results showed that PVP-S630 revealed a significant anti-wall sticking effect, with no notable change in the grain size of the spray drying power, increase in the fluidity, improvement in the moisture absorption and remarkable rise in the dissolution in vitro behavior of hyperoside. It was worth further studying the application of PVP-S630 in spray drying power of traditional Chinese medicine.
Absorption ; Desiccation ; methods ; Drug Compounding ; methods ; Drugs, Chinese Herbal ; chemistry ; Porosity ; Powders ; Pyrrolidines ; chemistry ; Vinyl Compounds ; chemistry ; Wettability

OBJECTIVETo study the role of oxiracetam on traumatic brain injury in rats.

METHODSThirty Wistar rats were randomly divided into 3 groups: sham operation group, model group and treatment group. Feeney method were used to establish traumatic brain injury (TBI) model in rats in model and treatment group, and rats in sham group were only broached without hydraumatic fitted. Rats in treatment group were successive administration for 21 days with oxiracetam (100 mg/kg, ig). Neurologic impairment scores were undertook after operation of 1 d, 4 d, 7 d, 14 d and 21 d, and Morris water maze test were proceeded during 15 to 19 days after operation. Average escape latency, searching time in target quadrant and number of crossing target platform in rats were recorded.

RESULTSNeurologic impairment scores of rats in treatment group were significantly less than those of model group after operation of 7, 14 and 21 d (P < 0.05). Average escape latency of model group were significantly higher than those of sham operation group and treatment group (P < 0.05, P < 0.01). Searching time in target quadrant and number of crossing target platform of model group were lower than those of sham operation and treatment group (P < 0.05)).

CONCLUSIONOxiracetam could decrease neural injury and increase ability of learning, memory and space cognition in traumatic brain injury rats.

Animals ; Brain Injuries ; drug therapy ; psychology ; Male ; Maze Learning ; drug effects ; Pyrrolidines ; pharmacology ; therapeutic use ; Rats ; Rats, Wistar

The microbial transformation of buflomedil by Cunninghamella blakesleana AS 3.153 was studied, as well as a microbial model which can be used to mimic metabolism of buflomedil in mammal was established. Experiments were conducted to screen the capabilities of four strains of Cunninghamella species to transform buflomedil, in which C. blakesleana AS 3.153 was selected for a preparative biotransformation. Furthermore, the microbial model was established based on the transformation condition optimization. The parent drug and its metabolites produced by C. blakesleana AS 3.153 were detected by liquid chromatography-mass spectrometry method and three metabolites were identified while two of them were new found metabolites. Two major metabolites, para-O-desmethyl buflomedil and 12-C-oxidated buflomedil, were isolated by semi-preparative HPLC. Based on the comparison between different species, the microbial transformation of buflomedil by C. blakesleana AS 3.153 is more similar to the metabolism of buflomedil in human and Beagle dog than that in rat.
Adult ; Animals ; Biotransformation ; Chromatography, High Pressure Liquid ; Cunninghamella ; metabolism ; Dogs ; Female ; Humans ; Male ; Molecular Structure ; Pyrrolidines ; chemistry ; pharmacokinetics ; Rats ; Rats, Wistar ; Spectrometry, Mass, Electrospray Ionization ; Young Adult

OBJECTIVETo synthesize novel cyanopyrrolidine-bearing compounds as dipeptidyl peptidase 4 (DPP4) inhibitors and characterize their biological activities in vitro.

METHODSEleven analogues of carbonitrilpyrrolidine were designed and synthesized by substitution reaction of (S)-2-(2-cyanopyrrolidin-1-yl)acetyl bromide with substituted phenyl piperazine pyridazinones.

RESULTSThe structures of the compounds were characterized by (1)H-NMR and MS spectra. Biological evaluation indicated that most of the compounds exhibited moderate inhibitory activities against DPP4.

CONCLUSIONThe preliminary bioassay indicates that all the synthesized compounds have moderate DPP-4 inhibition activity, especially the compounds 1j and 1k with inhibition rates reaching 26.14% and 34.15% at the concentration of 1×10(5) nmol/L, respectively.

Diabetes Mellitus, Type 2 ; drug therapy ; Dipeptidyl-Peptidase IV Inhibitors ; chemical synthesis ; chemistry ; Drug Design ; Humans ; Hypoglycemic Agents ; chemical synthesis ; chemistry ; Pyrrolidines ; chemistry

To investigate the role of activated nuclear factor-kappaB (NF-kappaB) in experimental allergic encephalomyelitis (EAE), the activity and protein expression of NF-kappaB p65 in rat brain tissues, which were extracted from EAE rats at 1, 7, 14 and 21 d respectively after EAE was induced by CFA-GPSCH, were measured with electrophoretic mobility shift assay and immunohistochemistry. The relationship between activated NF-kappaB and symptoms of EAE was also investigated. The results showed that protein expression level and the activity of NF-kappaB were very low in the brain of the control group. After EAE was induced, the activity of NF-kappaB and the level of the protein expression in the brains increased gradually with the development of symptoms and brain pathology of EAE. On d 14, both the activity and the level of protein expression in the brains reached a peak, the positive cells of NF-kappaB were mainly located at the choroid plexuses and subfornical organ, as well as around the regions of sleeve-like lesion foci, which were coincident with the locations of lesions of EAE. The incidence, symptoms, reduction of the body weight and pathology of EAE rats brains at the above locations were most significant. On d 21 the activity of NF-kappaB and level of the protein expression reduced gradually, which was in parallel with a gradual alleviation of the symptoms of EAE rats. After a specific inhibitor of NF-kappaB, PDTC was applied, the symptoms and pathological lesions of EAE rat brain were mitigated markedly. The above results indicate that the dynamic changes in the activity and protein expression of NF-kappaB were in parallel with the changes in symptoms and pathological lesion of EAE rat brains. In conclusion, the activated NF-kappaB in the brain may play a critical role in the pathogenesis of EAE, and application of some inhibitors of NF-kappaB, such as PDTC, may be one of the effective therapeutic methods for prevention and treatment of EAE.
Animals ; Brain ; metabolism ; Encephalomyelitis, Autoimmune, Experimental ; metabolism ; Female ; Pyrrolidines ; pharmacology ; Rats ; Rats, Wistar ; Thiocarbamates ; pharmacology ; Transcription Factor RelA ; antagonists & inhibitors ; metabolism