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

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

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

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

OBJECTIVETo investigate the expression of NF-kappaB in peripheral blood polymorphonuclear leukocyte (PMN) of acute pancreatitis (AP) and to assess the preventive effectiveness of pyrrolidine dithiocarbamate (PDTC) on NF-kappaB in vitro.

METHODSNineteen patients and 16 healthy individuals as control were enrolled in this study. The expression of NF-kappaB in PMNs was determined by gel electrophoretic mobility shift assay (EMSA). Routine clinical examination results and computed tomography findings of AP were recorded in all patients.

RESULTSThe PMNs from the patients with AP showed higher levels of NF-kappaB activities than those from control subjects (P < 0.01), severe acute pancreatitis (SAP) group showed much higher than mild acute pancreatitis (MAP) group (P < 0.05). In vitro, PDTC could reduce the NF-kappaB activity in PMNs of patients with AP, and its effectiveness at 2 mmol/L was stronger than at 1 mmol/L (P < 0.05). The PMNs from control subjects pretreated with 2 mmol/L PDTC before stimulation with the plasma from patients with SAP showed lower levels of NF-kappaB activities than did those untreated (P < 0.05).

CONCLUSIONThe NF-kappaB activation in peripheral blood PMNs participate in the course of acute pancreatitis and can be inhibited by PDTC in vitro.

Acute Disease ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; NF-kappa B ; biosynthesis ; blood ; Neutrophils ; drug effects ; metabolism ; Pancreatitis ; metabolism ; Pyrrolidines ; pharmacology ; Thiocarbamates ; pharmacology

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

While there are many therapies for type 2 diabetes are available including insulin secretagogues, insulin sensitizers and exogenous insulin, many patients are unable to reach recommended therapeutic targets. Incretin-based therapies have recently been introduced into clinical practice, and these novel therapies may make it possible to achieve improved glycemic control either with no weight gain (dipeptidyl peptidase-4 [DPP-4] inhibitors sitagliptin and vildagliptin, or with weight loss (glucagon-like peptide-1 [GLP-1] mimetics exenatide and liraglutide). This article aims to provide an overview of efficacy and safety data regarding incretinbased clinical trials in type 2 diabetic patients, and propose a systematic approach to treatment including patient selection and optimal treatment combination. In addition, preclinical data suggest that incretin-based therapies may also preserve-cell function. Therefore, these agents hold out promise of a truly disease-modifying therapy that would target the progressive nature of type 2 diabetes. Additional clinical trials will be required to test such hypothesis.
Adamantane ; Diabetes Mellitus, Type 2 ; Humans ; Incretins ; Insulin ; Nitriles ; Patient Selection ; Peptides ; Pyrazines ; Pyrrolidines ; Sitagliptin Phosphate ; Triazoles ; Venoms ; Weight Gain ; Weight Loss