Impact of different timing of consuming sweet snack on postprandial glucose excursions in healthy women.

AIMS: Our aim was to evaluate the acute effect of eating sweet snacks at different times of day on glycaemic parameters in young women without diabetes. METHODS: In this randomized controlled three-treatment crossover study, 17 women [(means ± SD) age: 21.2 ± 0.8 years, BMI: 20.7 ± 2.5 kg/m2, HbA1c: 36 ± 2 mmol/mol (5.1 ± 0.2%)] wore flash (continuous) glucose monitoring systems for 7 days. Each participant consumed identical test meals on days 4, 5 and 6, but consumed sweet snacks (baked cake: 498 kcal; 53.6 g of carbohydrate, 8.0 g of protein, 28.0 g of fat) at 12:30 (post-lunch), 15:30 (mid-afternoon) and 19:30 (post-dinner), respectively, on each of those days. Daily glycaemic parameters on those 3 days of snacking at different times of day were compared within-participant. RESULTS: The mean amplitude of glycaemic excursions (3.54 ± 0.32 vs. 2.73 ± 0.20 mmol/L; P < 0.05), standard deviation of glucose (1.20 ± 0.11 vs. 0.92 ± 0.07 mmol/L; P < 0.05), incremental area under the curve (IAUC) for glucose at 12:00-07:00 (986 ± 89 vs. 716 ± 88 mmol/L × min; P < 0.05) and IAUC at 07:00-10:00 the next day (141 ± 17 vs. 104 ± 12 mmol/L × min; P < 0.05) when the snack was eaten post-dinner were all significantly higher than with mid-afternoon snacking. CONCLUSION: Eating sweet snacks post-dinner should be avoided because it worsens glucose excursions as well as postprandial glucose levels after both dinner and the following day's breakfast in young healthy (non-diabetic) women.

Consuming snacks mid-afternoon compared with just after lunch improves mean amplitude of glycaemic excursions in patients with type 2 diabetes: A randomized crossover clinical trial.

AIMS: Our aim was to explore the acute effects of consuming snacks at different times on glucose excursions in patients with type 2 diabetes (T2D). METHODS: Seventeen patients with T2D [means±SD: age 67.4±9.4-years; BMI 23.5±3.1kg/m2; HbA1c 55±6mmol/mol (7.2±1.0%)] were randomly assigned in this crossover study. Each participant wore a continuous glucose monitoring device for 4 days and consumed identical test meals on the second and third days, comprising breakfast at 0700h, lunch at 1200h and dinner at 1900h. Half the participants consumed 75kcal biscuits at 1230h (just after lunch) on the second day and at 1530h (mid-afternoon) on the third day, while the other half consumed snacks at the same times, but vice versa. Each patient's glucose parameters were compared against baseline for the 2days of snacking at different times of day. RESULTS: Consuming snacks in the mid-afternoon led to significantly lower mean amplitudes of glycaemic excursions (mean±SEM: 5.19±0.48 vs. 6.90±0.69mmol/L, P<0.01; standard deviation: 1.75±0.17 vs. 2.16±0.21mmol/L, P<0.01) and incremental areas under the curve for glucose after dinner (479±76 vs. 663±104mmol/L per min, P<0.01) compared with snacking just after lunch, whereas mean glucose levels did not differ over the 2days. CONCLUSION: These results suggest that consuming snacks well separated from lunch may be an effective way to suppress postprandial glucose levels and glycaemic excursions.

Defect of the first-phase insulin secretion to glucose stimulation in the perfused pancreas of the nonobese diabetic (NOD) mouse.

To investigate the development of impaired insulin secretion in type I diabetes mellitus, the pancreata of ICR and NOD mice (10-50 wk of age) were perfused. According to insulin responses to 30 mM glucose and to 19 mM arginine, we classified the NOD mice into four groups: those having normal insulin secretion to glucose and to arginine similar to that of control ICR mice (group 1); those with a defect in the first-phase insulin secretion to glucose stimulation but with almost normal insulin secretion to arginine, total insulin release to glucose being significantly smaller than that of group 1 (group 2); those having only a small insulin response to either stimulus, but a fasting plasma glucose level still within the normal range (group 3); and those being overtly diabetic, showing no insulin response to either stimulus (group 4). The severity of insulitis and insulin concentration of the pancreas in each group of NOD mice was well correlated with the insulin release from the perfused pancreas. These results indicate that the initial sign of B-cell damage in NOD mice is a defect of the first phase of glucose-induced insulin secretion, which is followed by a total loss of ability to respond to glucose or arginine stimulation.

Ratio of motor nerve conduction velocity to F-wave conduction velocity in diabetic neuropathy.

OBJECTIVE: To investigate the usefulness of a new parameter, the ratio of motor nerve conduction velocity to F-wave conduction velocity (M/F ratio), for the differential diagnosis of diabetic neuropathy. RESEARCH DESIGN AND METHODS: Nerve conduction studies were conducted in 95 patients with diabetic neuropathy, 44 nondiabetic patients with peripheral neuropathy, and 24 normal control subjects. Nondiabetic patients with neuropathy were grouped by clinical diagnosis as follows: segmental demyelination (n = 15), axonal neuropathy (n = 11), alcoholic polyneuropathy (n = 4), and other polyneuropathy (n = 14). Motor nerve conduction velocity (MCV) of post-tibial nerves, sensory nerve conduction velocity (SCV) of sural nerves, and F-wave conduction velocity (FWCV) of post-tibial nerves were measured by standardized techniques. The M/F ratio was calculated from these measurements. RESULTS: The MCV and SCV of diabetic patients were significantly slower and the M/F ratio was significantly lower than those of normal subjects: MCV, 43.7 +/- 5.4 vs. 47.1 +/- 2.9 m/s, P < 0.001; SCV, 44.7 +/- 11.1 vs. 48.3 +/- 5.7 m/s, P < 0.05; M/F ratio, 0.84 +/- 0.09 vs. 0.90 +/- 0.06, P < 0.001. The FWCV of nondiabetic patients with neuropathy was significantly slower (40.0 +/- 6.3 vs. 48.3 +/- 4.0 m/s, P < 0.001) and the M/F ratio was significantly higher (1.04 +/- 0.12, P < 0.001) than that of normal subjects, respectively. Although MCV, SCV, and FWCV were correlated with age in normal control subjects, the M/F ratio was independent of age in the diabetic as well as the nondiabetic patients with neuropathy. CONCLUSIONS: Results suggest that the M/F ratio, which is influenced by the neuronal damages in the distal segment of peripheral nerves, is useful in the differential diagnosis of diabetic neuropathy.

High prevalence of mitochondrial diabetes mellitus in Japanese patients with major risk factors.

To identify diabetes mellitus caused by the mitochondrial gene substitution at genomic nucleotide pair 3243 (M3243A-->G) we selected 87 diabetic patients with high risk factors such as maternal inheritance and hearing loss. Total DNA was extracted from peripheral leukocytes, and mitochondrial DNA fragments containing M3243A-->G were amplified by polymerase chain reaction (PCR). The amplified fragments were digested with a restriction endonuclease Apa1 and analyzed by agarose gel electrophoresis. The incidence of the M3243A-->G mutation was 4.6% (four of 87) in diabetic patients with maternal inheritance and/or hearing loss. In a subgroup with both maternal inheritance and hearing loss, the incidence of the mutation was as high as 21.4% (three of 14). Cardiac disorders were also present in all four diabetic patients with the mutation. This study suggests that maternal inheritance and hearing loss are useful clinical findings to identify diabetic patients with the mutation, and that cardiac involvement is a high risk factor for the M3243A-->G mutation.

Antimicrobial constituents of Angelica dahurica roots.

One novel coumarin from Angelica dahurica roots was elucidated to be 5,8-di(2,3-dihydroxy-3-methylbutoxy)-psoralen. It occurs together with six other known coumarins and ferulic acid. The antimicrobial activity of the coumarins and ferulic acid were compared.

Islet cell surface antibodies preferentially inhibit glucose-stimulated insulin release in vitro.

The effect of islet surface antibodies (ICSA) on in vitro insulin release was studied. Isolated rat islets were incubated in the presence of immunoglobulin preparations from patients with insulin-dependent and non-insulin-dependent diabetes mellitus (IDDM, NIDDM) and healthy subjects, and stimulated with D-glucose, L-arginine or tolbutamide. After incubation, the amount of insulin release from the rat islets was determined. The immunoglobulin preparations from 5 newly diagnosed IDDM patients who were positive for ICSA, and from 5 age-matched healthy subjects were examined. Even in the absence of complement or lymphocytes, immunoglobulin fractions positive for ICSA significantly inhibited low and high concentrations of glucose-stimulated insulin release compared with normal control (P less than 0.02), but had little influence on insulin release after stimulation with tolbutamide. Arginine-stimulated insulin release was almost the same in ICSA-positive immunoglobulin fractions and the control. Immunoglobulin fractions negative for ICSA either from four patients with recently diagnosed IDDM or from four newly diagnosed NIDDM patients had only negligible effect on insulin release after stimulation with glucose. These results suggest that ICSA in IDDM patients, even in the absence of complement or lymphocytes, may preferentially interfere with the mechanisms of glucose-stimulated insulin release in the pancreatic B cells.

A simple assay for formate dehydrogenase activity by gas chromatography-mass spectrometry.

A new method using GC-MS was devised for the convenient measurement of formate dehydrogenase (FDH) activity in crude tissue samples. FDH activity was detected by measuring headspace 13CO2, which was enzymically converted from [13C]formic acid. This method proved to be sensitive and simple for the estimation of FDH activity without complicated pretreatment.

High-resolution analysis of polyprenols by supercritical fluid chromatography.

A high-resolution analysis of polyprenol mixtures was achieved by supercritical fluid chromatography (SFC). The separation of polyprenols was examined on an octadecylsilane-packed column with liquid carbon dioxide as the mobile phase and ethanol as modifier. Using this chromatography system, the resolution of separation (Rs) between octadecaprenol (prenol 18) and nonadecaprenol (prenol 19) was two times higher than that using conventional reversed-phase high-performance liquid chromatography. Our SFC technique allows the advantage of baseline separation of polyprenol samples containing hydrophobic components such as terpenes or fatty acids that are unfavorable for good separation. This method is very useful for the analysis of structurally close polyprenol analogues of rubber plant metabolites.

Fibrinogen Kanazawa: a congenital dysfibrinogenaemia with delayed polymerization having a replacement of proline-18 by leucine in the A alpha-chain.

Congenital dysfibrinogenaemia was found in a 39-year-old female and her two children. The proposita, apparently heterozygous for this abnormality, had no episode of bleeding or thrombosis. The abnormal fibrinogen showed normal release of fibrinopeptides A and B but impaired polymerization of the fibrin monomer. Amino acid sequence analysis of the whole A alpha-chain isolated from fibrinogen Kanazawa showed a substitution of Leu for Pro at position 18 in the A alpha-chain. This substitution was corroborated by the analysis of the amino acid sequence which demonstrated the lysyl endopeptidase peptides derived from the A alpha-chain of fibrinogen Kanazawa. The minimal genetic exchange responsible for this substitution was a C----T transition in the middle position of the Pro codon. We conclude that Pro-18 in the A alpha-chain is crucial for the polymerization of the fibrin monomer.

The occurrence of geometric polyprenol isomers in the rubber-producing plant, Eucommia ulmoides Oliver.

The chain length and geometric isomerism of polyprenols from Eucommia ulmoides Oliver were analyzed using supercritical fluid chromatography. After intensive effort to establish separation conditions for geometric isomers, a phenyl-bonded silica gel-packed column was found that cleanly separated poly-trans and -cis prenols. The presence of long-chain poly-trans prenols (>9 mers) was confirmed for the first time in plants. Trans isomers were found in the leaf, seed coat, and root, but not in the bark and seed. Poly-trans prenols in this plant may act as intermediates for trans-polyisoprene biosynthesis.

An artificial plastic receptor that discriminates axial asymmetry.

An artificial plastic receptor that can discriminate axial asymmetry of optically active binaphthyldiamine derivatives was prepared by the 'molecular imprinting' technique. A light-radical polymerization in the presence of an axially asymmetric compound, (R)-2,2'-bis-methylcarbonylamino-1,1'-binaphthyl (binaphthyldiamine bis-acetamide (BINADA-ac)) as a template molecule with methacrylic acid (MA) as a functional monomer, and ethyleneglycol dimethacrylate (EGDMA) as a crosslinker, at 4 degrees C. The obtained polymer exhibited a superior enantioselectivity to the (R)-enantiomer by HPLC analyses. This plastic receptor should recognize the template molecule with its shape and character of its functional groups. It should be useful in the development of chiral stationary phases for the optical resolutions of axially asymmetric compounds.

Effects of qigong walking on diabetic patients: a pilot study.

OBJECTIVES: The present study was designed to evaluate the advantages of qigong walking, a mild and slow exercise that uses all the muscles of the body, in comparison with conventional walking in patients with diabetes. INTERVENTIONS: Ten inpatients with diabetes mellitus and associated complications were studied on 3 different days. Either qigong walking (30-40-minute duration) or conventional walking was performed by the patients 30 minutes after lunch on 1 of the 3 study days. Plasma glucose levels and pulse rates were measured 30 minutes after lunch and again 20 minutes after exercising; that is, 90 minutes after lunch. These data were compared to those obtained on a day with no exercise after lunch. RESULTS: Plasma glucose levels decreased during both exercises (from 228 mg/dL before to 205 mg/dL after conventional walking) and (from 223 mg/dL before to 216 mg/dL after qigong walking). In both situations the results after exercise decreased more than those in the group with no exercise (229 mg/dL; p < 0.025). The pulse rates increased after conventional walking (from 77 to 95 beats per minute; p < 0.025) and were higher than those in the group with no exercise (70 beats per minute; p < 0.01) and those after qigong walking (79 beats per minute; p < 0.05). CONCLUSIONS: Qigong walking reduced plasma glucose after lunch without inducing a large increase in the pulse rate in patients with diabetes.

Effects of aspartame on diabetic rats and diabetic patients.

The effects of aspartame (L-aspartyl-L-phenylalanine methyl ester) on plasma glucose and insulin levels were investigated in diabetic rats and patients with non-insulin-dependent diabetes mellitus. The oral administration of 0.45 mg aspartame per 100g body weight, which is equivalent to 150 mg of glucose in sweetness, to streptozotocin-induced diabetic rats had no effect on the plasma glucose or insulin levels. Also, 225 mg oral aspartame loading, which is equivalent to 75 g of glucose in sweetness, to patients with non-insulin-dependent diabetes mellitus did not increase plasma glucose or insulin levels, although 75 g of oral glucose loading increased plasma glucose and insulin levels in diabetic patients as expected. Aspartame ingestion for three days at a dose of 24-48 mg per day and the intake of snacks flavored with 240 mg of aspartame also did not increase fasting plasma glucose levels. These results suggest that acute administration of aspartame has no influence on plasma glucose or insulin levels in diabetic rats and patients with non-insulin-dependent diabetes mellitus.

A new type of antimicrobial phenolics produced by plant peroxidase and its possible role in the chemical defense systems against plant pathogens.

Syringaldehyde readily reacted in the horse-radish peroxidase (HRPOD) system. The ethyl acetate extract of the reaction mixture showed a marked antimicrobial activity against bacteria and fungi. After repeated column chromatography three potential antimicrobial compounds were obtained from the extract. The structural elucidation of active compounds was achieved by a combination of spectroscopic techniques and chemical modification.

Identification of genes induced by taxol application using a combination of differential display RT-PCR and DNA microarray analysis.

The differential display reverse transcriptional polymerase chain reaction (DD-RT-PCR) was used to hunt for cDNA fragments specifically expressed by taxol treatment of HeLa cells. Forty-eight cDNA clones were differentially displayed through the experiments. The cDNA fragments obtained were separately spotted onto glass slides to prepare a tailor-made DNA chip. The gene expression pattern of differentially displayed cDNA fragments were checked by DNA microarray analysis.

Antifungal compounds induced in the dual culture with Phytolacca americana callus and Botrytis fabae.

In order to investigate new metabolites which are only induced in a plant callus infected by a pathogenic fungus, dual cultures with combinations of 10 species of fungi and 6 plant cell lines from different species were established. Among the combinations tested, the methanolic extract of a dual culture consisting of a plant cell line, Phytolacca americana and a fungus, Botrytis fabae showed a marked antifungal activity to Cladosporium herbarum. The main active constituent of this extract was identified to be phytolaccoside B (Pls B) by the spectroscopic analyses.

A cytotoxic principle of Tamarindus indica, di-n-butyl malate and the structure-activity relationship of its analogues.

Bioassay-guided fractionation of the methanolic extract of Tamarindus indica fruits led to the isolation of L-(-)-di-n-butyl malate which exhibited a pronounced cytotoxic activity against sea urchin embryo cells. In order to study structure-activity relationships, close-structure relatives of di-n-butyl malate were synthesized using D-(+)- and L-(-)-malic acid as starting materials, and their cytotoxic activities were examined for the sea urchin embryo assay. L-(-)-Di-n-pentyl malate was the most effective inhibitor to the development of the fertilized eggs. Significant inhibitory activity was not seen in the esters of D-(-)-isomer.

[Effect of bolus propofol administration on muscle evoked potential (MsEP) during spine surgery].

Intraoperative monitoring of descending pathways by means of muscle evoked potential (MsEP) is a reliable method to monitor spinal cord motor function, but MsEP is readily affected by anesthetics. We monitored MsEP evoked by repetitive transcranial electrical stimulation of the motor cortex in 30 patients receiving spine surgery. Total intravenous anesthesia was maintained with propofol and fentanyl without any muscle relaxant. Onset latencies and peak to peak amplitudes of MsEP were evaluated before and after the bolus propofol administration. The concentrations of propofol in blood and the effect-site during MsEP monitoring were predicted by computer simulation software. The amplitude of MsEP decreased slightly by bolus propofol administration, but the latencies showed no significant change with propofol under the same condition. We consider that total intravenous anesthesia with propofol and fentanyl without muscle relaxants is compatible with the recording of MsEP evoked by high frequency repetitive electrical transcranial stimulations. When MsEP is monitored during spine surgery, anesthetic condition should be controlled carefully in order to maintain a stable blood concentration of propofol and thus to assure the reliability of MsEP measurements.