No abstract available.
Adamantane ; Humans ; Nitriles ; Pyrrolidines

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

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

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

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 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

PURPOSE: Central nervous system (CNS) and cardiovascular system (CVS) side effects of anticholinergic agents used to treat overactive bladder (OAB) are underreported. Hence, this review aimed to focus on the mechanisms of CNS and CVS side effects of anticholinergic drugs used in OAB treatment, which may help urologists in planning the rationale for OAB treatment. MATERIALS AND METHODS: PubMed/MEDLINE was searched for the key words "OAB," "anticholinergics," "muscarinic receptor selectivity," "blood-brain barrier," "CNS," and "CVS side effects." Additional relevant literature was determined by examining the reference lists of articles identified through the search. RESULTS: CNS and CVS side effects, pharmacodynamic and pharmacokinetic properties, the metabolism of these drugs, and the clinical implications for their use in OAB are presented and discussed in this review. CONCLUSIONS: Trospium, 5-hydroxymethyl tolterodine, darifenacin, and solifenacin seem to have favorable pharmacodynamic and pharmacokinetic properties with regard to CNS side effects, whereas the pharmacodynamic features of darifenacin, solifenacin, and oxybutynin appear to have an advantage over the other anticholinergic agents (tolterodine, fesoterodine, propiverine, and trospium) with regard to CVS side effects. To determine the real-life situation, head-to-head studies focusing especially on CNS and CVS side effects of OAB anticholinergic agents are urgently needed.
Benzhydryl Compounds ; Benzilates ; Benzofurans ; Cardiovascular System* ; Central Nervous System* ; Cholinergic Antagonists* ; Cresols ; Mandelic Acids ; Metabolism ; Pyrrolidines ; Quinuclidines ; Receptors, Muscarinic ; Tetrahydroisoquinolines ; Urinary Bladder, Overactive* ; Solifenacin Succinate

New therapeutics for type 2 diabetes using incretin hormone were introduced recently. Incretin-based therapies consist of two types: GLP-1 agonists mainly acting on the GLP-1 receptor and dipeptidyl peptidase 4 inhibitors (DPP-4 inhibitors). The former is resistant to DPP-4 and injectable. The latter is oral medications raising endogenous GLP-1 by inhibiting the degrading enzyme DPP-4. The incretin based therapies are promising and more commonly used due to their action and safety profile. Stimulation of insulin secretion by these drugs occurs in a glucose-dependent manner. Incretin based therapies have low risk for hypoglycemia. The subsequent review outlines evidence from selected clinical trials of the currently available GLP-1 agonists, exenatide and liraglutide, and DPP-4 inhibitors, sitagliptin and vildagliptin.
Adamantane ; Dipeptidyl-Peptidase IV Inhibitors ; Glucagon-Like Peptide 1 ; Hypoglycemia ; Incretins ; Insulin ; Nitriles ; Peptides ; Pyrazines ; Pyrrolidines ; Receptors, Glucagon ; Triazoles ; Venoms ; Glucagon-Like Peptide-1 Receptor ; Liraglutide ; Sitagliptin Phosphate

BACKGROUND: The present study investigated the efficacy and safety of vildagliptin-metformin treatment compared to those of glimepiride-metformin treatment for type 2 diabetes. METHODS: In a randomized, open-label, comparative study, 106 patients with type 2 diabetes were enrolled. The primary endpoint was a reduction in HbA1c from baseline and secondary endpoints included fasting plasma glucose (FPG) or 2-hour postprandial glucose (2h-PPG) reduction from baseline, as well as HbA1c responder rate and HbA1c reduction according to baseline HbA1c category. RESULTS: Comparable HbA1c reduction was observed with a mean+/-standard deviation change from baseline to the 32-week endpoint of -0.94+/-1.15% in the vildagliptin group and -1.00+/-1.32% in the glimepiride group. A similar reduction in 2h-PPG (vildagliptin group 3.53+/-4.11 mmol/L vs. the glimepiride group 3.72+/-4.17 mmol/L) was demonstrated, and the decrements in FPG (vildagliptin group 1.54+/-2.41 mmol/L vs. glimepiride group 2.16+/-2.51 mmol/L) were not different between groups. The proportion of patients who achieved an HbA1c less than 7% at week 32 was 50.1% in the vildagliptin group and 56.0% in the glimepiride group. An average body weight gain of 2.53+/-1.21 kg in the glimepiride group was observed in contrast with the 0.23+/-0.69 kg weight gain noted in the vildagliptin group. A 10-fold lower incidence of hypoglycemia was demonstrated in the vildagliptin group, in addition to an absence of severe hypoglycemia. CONCLUSION: Vildagliptin-metformin treatment provided blood glucose control efficacy comparable to that of glimepiride-metformin treatment and resulted in better adverse event profiles with lower risks of hypoglycemia and weight gain.
Adamantane ; Blood Glucose ; Body Weight ; Diabetes Mellitus, Type 2 ; Fasting ; Glucose ; Humans ; Hypoglycemia ; Incidence ; Metformin ; Nitriles ; Plasma ; Pyrrolidines ; Sulfonylurea Compounds ; Weight Gain