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Effect of ninjin'yoeito, a Kampo (traditional Japanese) medicine, on cognitive impairment and depression in patients with Alzheimer's disease: 2 years of observation.
Kudoh, C, Arita, R, Honda, M, Kishi, T, Komatsu, Y, Asou, H, Mimura, M
Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society. 2016;(2):85-92
Abstract
BACKGROUND Only a few approved drugs are capable of alleviating the cognitive and behavioural symptoms of people living with Alzheimer's disease (AD). In recent years, however, the number of studies examining the clinical effects of herbal medicines on cognitive function in patients with AD has increased considerably. This study evaluated the long-term effects of a traditional Japanese medicine (Kampo medicine) known as ninjin'yoeito (NYT) on cognitive impairment and mood status in patients with AD over a 2-year period. METHODS Twenty-three patients with mild-to-moderate probable AD according to the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria were included. Each participant had exhibited an insufficient response to treatment with donepezil alone before the start of the trial. Eleven patients received treatment with donepezil alone, and the remaining patients received a combined treatment of donepezil and NYT for 2 years. Patients were assessed by the Mini-Mental State Examination and the Alzheimer's Disease Assessment Scale-cognitive component-Japanese version for cognitive function, and the Neuropsychiatric Inventory was used to evaluate the patients' mood status at baseline and every 6 months for 2 years. RESULTS The Mini-Mental State Examination results showed no significant differences between the two groups. Significant improvements were observed on the Alzheimer's Disease Assessment Scale-cognitive component-Japanese version and the Neuropsychiatric Inventory depression scores of patients who received the combined therapy with donepezil and NYT (Alzheimer's Disease Assessment Scale-cognitive component-Japanese version, 12 months: P < 0.01, 18 months: P = 0.04, 24 months: P < 0.01; Neuropsychiatric Inventory depression, 6 months: P < 0.05, 24 months: P < 0.05). CONCLUSIONS A 2-year follow-up of patients receiving donepezil and NYT treatment showed an improved cognitive outcome and alleviation of AD-related depression.
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NeuroD1 A45T and PAX4 R121W polymorphisms are associated with plasma glucose level of repaglinide monotherapy in Chinese patients with type 2 diabetes.
Gong, ZC, Huang, Q, Dai, XP, Lei, GH, Lu, HB, Yin, JY, Xu, XJ, Qu, J, Pei, Q, Dong, M, et al
British journal of clinical pharmacology. 2012;(3):501-9
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Abstract
AIMS: We aimed to determine whether NeuroD1/BETA2 and PAX4 polymorphisms were associated with the therapeutic efficacy of repaglinide in Chinese type 2 diabetes mellitus (T2DM) patients. METHODS Three hundred and sixty-eight T2DM patients and 132 healthy control subjects were genotyped by restriction fragment length polymorphism. Forty-three patients with various genotypes were randomly selected to undergo 8 weeks of repaglinide treatment (3 mg day(-1)). Fasting plasma glucose, postprandial plasma glucose, glycated haemoglobin, fasting and postprandial serum insulin (FINS, PINS), homeostasis model assessment for insulin resistance, serum triglyceride, total cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol were determined before and after repaglinide treatment. RESULTS The allelic frequency of NeuroD1/BETA2 T45 was higher in T2DM patients than in the control subjects [13.45 vs. 6.82%, P < 0.01, odds ratios = 2.342 (1.365, 4.019), P= 0.002]. Type 2 diabetes mellitus patients with the mutated allele of NeuroD1/BETA2 A45T polymorphism showed higher FINS (13.46 ± 12.57 vs. 10.04 ± 7.09 mU l(-1) , P < 0.05) (11.67, 14.83 vs. 8.38, 11.37) and PINS (52.11 ± 40.93 vs. 68.66 ± 43.87 mU l(-1), P < 0.05) (44.89, 58.35 vs. 55.35, 88.87) than individuals with the T allele. The PAX4 R121W R allele carriers had higher PINS (52.11 ± 40.93 vs. 68.66 ± 43.87 mU l(-1), P < 0.05) (44.89, 58.35 vs. 55.35, 88.87) than subjects with the W allele. After repaglinide treatment, patients with the T allele of NeuroD1/BETA2 A45T polymorphisms had attenuated efficacy on fasting plasma glucose (-2.79 ± 2.14 vs.-0.99 ± 1.80 mmol l(-1), P < 0.01) (-3.53, -1.84 vs.-1.99, -0.13) and postprandial plasma glucose (-6.71 ± 5.90 vs.-2.54 ± 3.39 mmol l(-1), P < 0.01) (-9.28, -4.62 vs.-4.34, -0.84). Patients with the RR genotype of PAX4 R121W showed better efficacy with respect to the level of postprandial plasma glucose than R/W genotypes (-6.53 ± 6.52 vs.-2.95 ± 1.17 mmol l(-1), P < 0.05) (-8.20, -4.89 vs.-3.92, -1.20). CONCLUSIONS The NeuroD1/BETA2 and PAX4 polymorphisms were substantially associated with plasma glucose level after repaglinide monotherapy.
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Opiate-induced dopamine release is modulated by severity of alcohol dependence: an [(18)F]fallypride positron emission tomography study.
Spreckelmeyer, KN, Paulzen, M, Raptis, M, Baltus, T, Schaffrath, S, Van Waesberghe, J, Zalewski, MM, Rösch, F, Vernaleken, I, Schäfer, WM, et al
Biological psychiatry. 2011;(8):770-776
Abstract
BACKGROUND Preclinical data implicate the reinforcing effects of alcohol to be mediated by interaction between the opioid and dopamine systems of the brain. Specifically, alcohol-induced release of β-endorphins stimulates μ-opioid receptors (MORs), which is believed to cause dopamine release in the brain reward system. Individual differences in opioid or dopamine neurotransmission have been suggested to be responsible for enhanced liability to abuse alcohol. In the present study, a single dose of the MOR agonist remifentanil was administered in detoxified alcohol-dependent patients and healthy control subjects to mimic the β-endorphin-releasing properties of ethanol and to assess the effects of direct MOR stimulation on dopamine release in the mesolimbic reward system. METHODS Availability of D(2/3) receptors was assessed before and after single-dose administration of the MOR agonist remifentanil in 11 detoxified alcohol-dependent patients and 11 healthy control subjects with positron emission tomography with the radiotracer [(18)F]fallypride. Severity of dependence as assessed with the Alcohol Use Disorders Identification Test was compared with remifentanil-induced percentage change in [(18)F]fallypride binding (Δ%BP(ND)). RESULTS The [(18)F]fallypride binding potentials (BP(ND)s) were significantly reduced in the ventral striatum, dorsal putamen, and amygdala after remifentanil application in both patients and control subjects. In the patient group, ventral striatum Δ%BP(ND) was correlated with the Alcohol Use Disorders Identification Test score. CONCLUSIONS The data provide evidence for a MOR-mediated interaction between the opioid and the dopamine system, supporting the assumption that one way by which alcohol unfolds its rewarding effects is via a MOR-(γ-aminobutyric acid)-dopamine pathway. No difference in dopamine release was found between patients and control subjects, but evidence for a patient-specific association between sensitivity to MOR stimulation and severity of alcohol dependence was found.
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Enhancement of early- and late-phase insulin secretion and insulin sensitivity by the combination of repaglinide and metformin in type 2 diabetes mellitus.
Rudovich, NN, Leyck Dieken, MG, Rochlitz, H, Pfeiffer, AF
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2004;(7):395-400
Abstract
The effects of a combination of repaglinide and metformin on the insulin secretion pattern and insulin sensitivity were studied in a fixed-dose, open-label, placebo-controlled cross-over study. Eleven patients with T2 DM were allocated in random order to treatment with placebo or repaglinide (1 mg pre-meal 3 x/day) in combination with metformin (2550 mg/day) for one-week periods of each. At the end of each period a hyperglycaemic (HC) and a euglycaemic clamp (EC) were performed. Both early (0 - 10 min) and late (25 - 180 min) phases of insulin secretion were significantly increased during HC with repaglinide compared to placebo (263.3 +/- 133.1 vs. 443.6 +/- 138.5 pmol/l/10 min, p = 0.008 and 18 750.9 +/- 5936.4 vs. 34 508.65 +/- 9234.0 pmol/l/25 - 180 min; p = 0.008). The C-peptide concentrations under steady-state conditions were lower in EC with placebo than with repaglinide (p = 0.014). When euglycaemia was achieved in EC, the C-peptide concentrations decreased from hyperglycaemic to normoglycaemic values in the presence of repaglinide but remained higher than after placebo. The insulin sensitivity index (ISI) was increased by 35 % after 1 week of combination therapy with repaglinide plus metformin (1.11 +/- 0.03 x 10 (2) vs. 0.83 +/- 0.21 x 10 (2) mg x kg (-1) body weight x min (-1) x pmol (-1) x l, respectively; p = 0.033). Repaglinide increased early and late phases of insulin responses in HC, without markedly enhancing insulin secretion in euglycaemia. Repaglinide in combination with metformin produced a significant enhancement of ISI, suggesting a synergistic effect on insulin sensitivity.
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The effects of diet, sulfonylurea, and Repaglinide therapy on clinical and metabolic parameters in type 2 diabetic patients during Ramadan.
Sari, R, Balci, MK, Akbas, SH, Avci, B
Endocrine research. 2004;(2):169-77
Abstract
BACKGROUND AND AIM Diabetes and its treatment can cause problems for the Muslim population. The aim of this study was to evaluate the effect of different therapy models on clinical and metabolic status in type 2 diabetic patients during Ramadan. MATERIAL AND METHODS Fifty-two type 2 diabetic patients were included to this study. Twelve of patients were on diabetic diet only before and during Ramadan (Group 1). Forty of patients had had sulfonylurea (Glimepiride 23 patients, gliclazide 17 patients) before Ramadan. Thirteen of these patients were on a single dose sulfonylurea (Glimepiride 8 patients, gliclazide 5 patients) (Group 2) and 27 were on Repaglinide 2 x 2 mg (Group 3) during Ramadan. Beta-hydroxybutyric acid, glucose, fructosamine, HbA1c, lipid levels and body weight were measured before and after Ramadan. RESULTS Body weight, fasting plasma glucose, fructosamine, HbA1c, total cholesterol were not changed in groups during the study. Triglyceride level decreased after Ramadan in groups 2 (p = 0.002) and 3 (p = 0.024). HDL-cholesterol level increased in group 3 (p = 0.022). Fasting capillary beta-hydroxybutyric acid level increased in group 1 (p = 0.034) and didn't change in groups 2 and 3 during the Ramadan. Only one hypoglycemic event occurred at day 6 of Ramadan in patients in group 2 (the patient was on 3 mg glimepiride). CONCLUSION Our results conclude that Ramadan fasting affects metabolic parameters in type 2 diabetes and hypoglycemia should be kept in mind especially in patients using sulfonylurea treatment. Ramadan fasting is not advised for type 2 diabetics while taking medical therapy. If the patient wants Ramadan fasting, these patients using Repaglinide can reduce the frequency of hypoglycemia.
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Lack of effect of acute repaglinide administration on postprandial lipaemia in patients with type 2 diabetes mellitus.
Tentolouris, N, Kolia, M, Tselepis, AD, Perea, D, Kitsou, E, Kyriaki, D, Tambaki, AP, Karabina, SP, Sala, C, Fragoulopoulos, E, et al
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2003;(6):370-3
Abstract
The effect of acute repaglinide administration (2 mg) on postprandial glycaemia and lipaemia has been examined in 20 subjects with type 2 diabetes mellitus. Each subject received in the morning, after a 12 to 14 h fast, a standard mixed meal (total energy 783 kcal), preceded by one tablet of 2 mg repaglinide or placebo. Chylomicrons and chylomicron-deficient plasma were prepared by ultracentrifugation. Triglyceride levels in CM fraction (CM-triglycerides) in total plasma as well as in CM-deficient plasma (non-CM-triglycerides) were determined. A significant reduction in postprandial glycaemia was observed after repaglinide administration compared to placebo ( p < 0.001). Plasma concentrations of total triglycerides, CM-triglycerides, non-CM-triglycerides, free fatty acids and the other plasma lipids measured, were not significantly different between the two phases of the study. It is concluded that, in contrast to sulphonylureas, acute repaglinide administration does not improve postprandial lipaemia in patients with type 2 diabetes.
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Decreased 5-HT2a receptor binding in patients with anorexia nervosa.
Audenaert, K, Van Laere, K, Dumont, F, Vervaet, M, Goethals, I, Slegers, G, Mertens, J, van Heeringen, C, Dierckx, RA
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2003;(2):163-9
Abstract
UNLABELLED Indirect estimations of brain neurotransmitters in patients with anorexia nervosa (AN) and low weight have demonstrated a reduction in brain serotonin (5-HT) turnover in general and led to hypotheses about dysfunction in the 5-HT(2a) receptor system. It was our aim to investigate the central 5-HT(2a) receptor binding index using SPECT brain imaging. METHODS The 5-HT(2a) receptors of low-weight patients with AN were studied by means of the highly specific radioiodinated 5-HT(2a) receptor antagonist 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide or (123)I-5-I-R91150. Fifteen patients with clinical diagnoses of AN and 11 age-matched healthy volunteers received intravenous injections of 185 MBq (123)I-5-I-R91150 and were scanned with high-resolution brain SPECT. RESULTS Compared with healthy volunteers, patients with AN had a significantly reduced 5-HT(2a) binding index in the left frontal cortex, the left and right parietal cortex, and the left and right occipital cortex. A significant left-right asymmetry was noted in the frontal cortex (left < right). CONCLUSION These results are in accordance with diminished metabolic and perfusion of frontal and parietal cortices reported in recent neuroimaging studies and imply localized disturbed serotonergic function. The data are discussed in the light of possible confounding factors related to the low-weight AN status. A regional cortical reduction in 5-HT(2a) binding index is not likely to be caused by a general reduction in serotonergic function due to the possible confounding factors. Suggestions for further research are given.
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Therapeutic effects of an acetylcholinesterase inhibitor (donepezil) on memory in Wernicke-Korsakoff's disease.
Sahin, HA, Gurvit, IH, Bilgiç, B, Hanagasi, HA, Emre, M
Clinical neuropharmacology. 2002;(1):16-20
Abstract
Wernicke-Korsakoff's disease (WKD) is cognitively an amnestic state resulting from strategic lesions in the limbic system subserving the episodic memory network and resulting from thiamine deficiency. Neurochemical deficits have been implicated in the pathophysiology of amnesia based on the pathologic observations that various brainstem and basal forebrain nuclei are also affected. Previous treatment attempts with serotoninergic, noradrenergic, and cholinergic drugs have given controversial results. The objective of this study was to assess the effects of a cholinesterase inhibitor, donepezil, on memory, attention, and executive functions in patients with nonalcoholic WKD. Seven patients who developed WKD after a hunger strike were included in this single, blind, placebo-controlled, one-way, crossover study. The patients were administered donepezil during the first 30 days, and were administered placebo during the following 30 days. Neuropsychological tests to evaluate verbal and visual memory, and attention and executive function were performed on days 0, 31, and 61. All patients completed both phases of the study. There were no statistically significant differences between the three evaluations, except for a difference between active treatment and the placebo phase during recall of the Rey-Osterrieth complex figure, which was in favor of the placebo phase. There were no significant changes in favor of the active treatment. Cholinergic treatment with the cholinesterase inhibitor donepezil does not seem to provide marked beneficial effects in patients with WKD in this small, descriptive study. This may be because pathways mediating channel and state-dependent functions are impaired in this disease, and enhancement of state-dependent cholinergic transmission may not be sufficient. Subtle benefits, however, cannot be excluded because of the small sample size and the relatively short duration of the treatment.