High Carbohydrate Diet Increased Glucose Transporter Protein Levels in Jejunum but Did Not Lead to Enhanced Post-Exercise Skeletal Muscle Glycogen Recovery

We examined the effect of dietary carbohydrate intake on post-exercise glycogen recovery. Male Institute of Cancer Research (ICR) mice were fed moderate-carbohydrate chow (MCHO, 50%cal from carbohydrate) or high-carbohydrate chow (HCHO, 70%cal from carbohydrate) for 10 days. They then ran on a treadmill at 25 m/min for 60 min and administered an oral glucose solution (1.5 mg/g body weight). Compared to the MCHO group, the HCHO group showed significantly higher sodium-D-glucose co-transporter 1 protein levels in the brush border membrane fraction (p = 0.003) and the glucose transporter 2 level in the mucosa of jejunum (p = 0.004). At 30 min after the post-exercise glucose administration, the skeletal muscle and liver glycogen levels were not significantly different between the two diet groups. The blood glucose concentration from the portal vein (which is the entry site of nutrients from the gastrointestinal tract) was not significantly different between the groups at 15 min after the post-exercise glucose administration. There was no difference in the total or phosphorylated states of proteins related to glucose uptake and glycogen synthesis in skeletal muscle. Although the high-carbohydrate diet significantly increased glucose transporters in the jejunum, this adaptation stimulated neither glycogen recovery nor glucose absorption after the ingestion of post-exercise glucose.     

Slow inhibitory potentials in the teleost Mauthner cell

In vivo recordings from Mauthner cells in adult zebrafish (Danio rerio) and goldfish (Carassius auratus) preparations with potassium chloride filled electrodes revealed a new class of long-lasting synaptic events in these cells. Their decay time constant ranged from 20 to 80ms, which is about 20 times longer than that of previously identified fast glycinergic inhibitory postsynaptic potentials in this neuron. The average time to peak of these slow events ranged from 1 to 6ms. We demonstrated that they are also inhibitory since (i) they were resistant to antagonists of the excitatory glutamatergic receptors; (ii) their amplitude was increased following chloride loading of the Mauthner cell; (iii) their reversal potential was the same as that of fast, glycinergic inhibitory postsynaptic potentials; and (iv) they produced an inhibitory shunt of the cell's membrane resistance. Furthermore, as with the fast inhibitory postsynaptic potentials, the decay time of the slow events is voltage dependent, increasing when the Mauthner cell is depolarized. However, these inhibitory postsynaptic potentials had a different pharmacological profile to the fast glycinergic ones. That is, they persisted in the presence of strychnine at doses that abolished the fast ones and they were more sensitive to bicuculline. These data are compatible with the notion that these inhibitory postsynaptic potentials are mediated by activation of a different inhibitory receptor type, and may be GABAergic. In addition, the decay time constant of the fast inhibitory postsynaptic current was shorter than the first of the two components that contribute to the bi-exponential decay reported previously for miniature inhibitory postsynaptic currents in Mauthner cells of larval zebrafish. This suggests developmental modifications and/or a switch in the assembly of glycine receptor subtypes. While amplitude distributions of the fast miniature inhibitory postsynaptic potentials recorded in the presence of tetrodotoxin generally could fit with a single Gaussian function, the amplitude histograms of slow miniature events were skewed, often with multiple nearly equally spaced peaks, consistent with the synchronous release of several quantal units. These previously undescribed slow unitary inhibitory postsynaptic potentials contribute to inhibitory synaptic noise recorded in the Mauthner cells. Specifically, autocorrelation analysis revealed gamma-like rhythms (30-80Hz) in each of two phases, characterized as "noisy" and "quiet", and dominated by the fast and slow inhibitory postsynaptic potentials, respectively. The major frequencies of these two states were significantly different (i.e. around 90 and 40Hz, respectively), suggesting that the fast and slow inhibitory postsynaptic potentials are derived from different inhibitory networks. Chloride-filled Mauthner cells gradually hyperpolarized in the presence of tetrodotoxin, reflecting the effect of ongoing activity in the interneurons that produce the slow events. We conclude that this new class of inhibitory postsynaptic potentials contributes to the tonic inhibition which controls the Mauthner cell's excitability. In physiological conditions, this regulatory influence is expressed as a continuous shunt of this neuron's input resistance and responsiveness to sensory inputs.     

A preliminary study of the reliability of immediate vs delayed interviews of cardiac arrest witnesses

Introduction. Methods to characterize the interval between a collapse from cardiac arrest until a 911 call is made have not yet been developed. Objective. To determine the concordance of cardiac arrest data obtained by two methods: an immediate nurse interview of out-of-hospital cardiac arrest (OHCA) witnesses, and a follow-up phone interview performed two weeks later. Methods. This was a prospective study of OHCA witnesses dating from January 1997 to May 1998. Witnesses were briefly interviewed at the time of emergency department presentation, and two weeks later a more lengthy structured phone interview was performed. The authors identified key data elements: 1) was the arrest witnessed? (Wit); 2) was CPR administered prior to EMS arrival? (BCPR); 3) was the first call placed to 911? (c911); and 4) was the estimated collapse to call interval <4 minutes? (ECCI). The analysis utilized Cohen's kappa statistic and Spearman's correlation coefficient. Results. A convenience sample of 42 matched pairs of OHCA cases was analyzed. Kappa statistics for agreement between methods were: 1) Wit(κ = 0.750), 2)BCPR(κ = 0.892),3) c911(κ = 0.892), and 4) ECCI(κ = 0.571, Spearman's 0.528). Conclusion. There is good to excellent agreement between immediate and phone interview data retrieval methods. Phone interviews appear to yield data comparable to that with the more difficult and expensive, direct interview method.     

CD56+ cells are recruited to the uterus in two waves: at ovulation and during the first 2 weeks after missed menses

PROBLEM: Uterine natural killer (uNK) cells are enriched in the post-ovulatory uterus and during pregnancy. Whether these cells arise from blood pre-cursors or from stem cells in the uterus is undefined. To support a hypothesis that precursors of uNK cells are recruited from blood, adhesive function of blood CD56+ subsets were assessed during one cycle and during pregnancy. METHOD OF STUDY: Fifteen women of proven fertility provided serial blood samples during one menstrual cycle and thirty women with a history of implantation failure or recurrent spontaneous abortion provided serial samples during infertility treatment. RESULTS: CD56(bright) cells, but not CD56(dim) cells or NKT cells, increased in ligand-binding capacity during ovulation in fertile cycles only and during the first 2 weeks from date of missed menses. CONCLUSION: Enhanced adhesive function at ovulation in CD56(bright) cells in fertile cycles and during early gestation supports a hypothesis of recruitment of pre-uNK cells from the blood CD56(bright) subset.     

The relation between cognitive function and UI in healthy, community-dwelling, middle-aged and elderly people

The aim of this study was to examine the relation between UI and cognitive function among non-disabled middle-aged and elderly community-dwelling people. A total of 201 participants (86 men and 115 women) were given a structured questionnaire regarding their condition of UI as well as a cognitive assessment battery (memory, attention, verbal fluency, information processing speed, and visuospatial function). The results showed a significant relation between UI and cognitive tasks for letter fluency, attention, and information processing speed, while no relation was found in cognitive tasks for memory and visuospatial function. Based on these findings, possible mechanisms regarding the relation between UI and cognitive function, and preventive methods to reduce the prevalence of UI in middle-aged and upper middle-aged community dwellers are discussed.     

Family with MSH2 mutation presenting with keratoacanthoma and precancerous skin lesions

Muir–Torre syndrome (MTS) is a familial cancer syndrome characterized by a predisposition to keratoacanthoma (KA) and sebaceous tumors. Although MTS and hereditary non‐polyposis colorectal cancer (HNPCC) share the same genetic alterations in mismatch repair (MMR) genes, the other skin lesions in MTS or HNPCC have been only rarely reported. We report a family with an MSH2 mutation c.1126_1127delTT (p.Leu376Thrfs*12). A 46‐year‐old male proband developed KA with sebaceous differentiation, colon cancer and gastric cancer, and fulfilled the diagnostic criteria for MTS. His 80‐year‐old mother, diagnosed with HNPCC, presented with multiple gastrointestinal tract cancers, Bowen's disease and actinic keratosis. Immunostaining revealed attenuated MSH2 protein expression in KA, as well as in Bowen's disease and actinic keratosis lesions. These findings suggest that MMR gene abnormality is also critical in the development of benign or malignant cutaneous tumors such as actinic keratosis and Bowen's disease in MTS/HNPCC patients.     

Usefulness of docetaxel as first‐line chemotherapy for metastatic extramammary Paget's disease

In invasive extramammary Paget's disease (EMPD), distant metastases may develop and the condition may become fatal; however, no standardized treatment has been established. Although based on only a few cases, several chemotherapy regimens were reported to be promising. We conducted a multicenter, retrospective study to evaluate the efficacy of docetaxel for metastatic EMPD. We retrospectively collected data on 18 metastatic EMPD patients treated using docetaxel from 1998 to 2012 in 12 institutes in Japan. The following clinical data were collected: tumor response, time to progression, overall survival and adverse effects. Of those, three patients treated combined with S‐1, one patient treated with weekly schedule and one patient treated combined with radiotherapy were excluded from the further analysis. All 13 patients received monthly docetaxel as the first‐line treatment. The average number of treatment cycles was 9.1. Among the 12 patients with a confirmed response, seven (58%) showed a partial response, three (25%) stable disease and two (17%) progressive disease. The disease control rate (partial response + stable disease) was as high as 83%. The time to progression and median overall survival were 7.1 and 16.6 months, respectively. The 1‐year overall survival rate determined by the Kaplan–Meier method was 75.0%. All adverse effects were manageable and no treatment‐related deaths were observed. The high disease control rate and overall survival shown by this study suggest that first‐line use of docetaxel may be a promising treatment for metastatic EMPD. A prospective clinical trial is required to confirm our results.