Alteration of primary afferent activity following inferior alveolar nerve transection in rats

<p>Abstract</p> <p>Background</p> <p>In order to evaluate the neural mechanisms underlying the abnormal facial pain that may develop following regeneration of the injured inferior alveolar nerve (IAN), the properties of the IAN innervated in the mental region were analyzed.</p> <p>Results</p> <p>Fluorogold (FG) injection into the mental region 14 days after IAN transection showed massive labeling of trigeminal ganglion (TG). The escape threshold to mechanical stimulation of the mental skin was significantly lower (i.e. mechanical allodynia) at 11-14 days after IAN transection than before surgery. The background activity, mechanically evoked responses and afterdischarges of IAN Aδ-fibers were significantly higher in IAN-transected rats than naive. The small/medium diameter TG neurons showed an increase in both tetrodotoxin (TTX)-resistant (TTX-R) and -sensitive (TTX-S) sodium currents (<it>I</it>_Na) and decrease in total potassium current, transient current (<it>I</it>_A) and sustained current (<it>I</it>_K) in IAN-transected rats. The amplitude, overshoot amplitude and number of action potentials evoked by the depolarizing pulses after 1 μM TTX administration in TG neurons were significantly higher, whereas the threshold current to elicit spikes was smaller in IAN-transected rats than naive. Resting membrane potential was significantly smaller in IAN-transected rats than that of naive.</p> <p>Conclusions</p> <p>These data suggest that the increase in both TTX-S <it>I</it>_Naand TTX-R <it>I</it>_Naand the decrease in <it>I</it>_Aand <it>I</it>_kin small/medium TG neurons in IAN-transected rats are involved in the activation of spike generation, resulting in hyperexcitability of Aδ-IAN fibers innervating the mental region after IAN transection.</p

Enhancement of protein production via the strong DIT1 terminator and two RNA-binding proteins in Saccharomyces cerevisiae

Post-transcriptional upregulation is an effective way to increase the expression of transgenes and thus maximize the yields of target chemicals from metabolically engineered organisms. Refractory elements in the 3′ untranslated region (UTR) that increase mRNA half-life might be available. In Saccharomyces cerevisiae, several terminator regions have shown activity in increasing the production of proteins by upstream coding genes; among these terminators the DIT1 terminator has the highest activity. Here, we found in Saccharomyces cerevisiae that two resident trans-acting RNA-binding proteins (Nab6p and Pap1p) enhance the activity of the DIT1 terminator through the cis element GUUCG/U within the 3′-UTR. These two RNA-binding proteins could upregulate a battery of cell-wall–related genes. Mutagenesis of the DIT1 terminator improved its activity by a maximum of 500% of that of the standard PGK1 terminator. Further understanding and improvement of this system will facilitate inexpensive and stable production of complicated organism-derived drugs worldwide

Potassium channels as a potential therapeutic target for trigeminal neuropathic and inflammatory pain

Previous studies in several different trigeminal nerve injury/inflammation models indicated that the hyperexcitability of primary afferent neurons contributes to the pain pathway underlying mechanical allodynia. Although multiple types of voltage-gated ion channels are associated with neuronal hyperexcitability, voltage-gated K+ channels (Kv) are one of the important physiological regulators of membrane potentials in excitable tissues, including nociceptive sensory neurons. Since the opening of K+ channels leads to hyperpolarization of cell membrane and a consequent decrease in cell excitability, several Kv channels have been proposed as potential target candidates for pain therapy. In this review, we focus on common changes measured in the Kv channels of several different trigeminal neuropathic/inflammatory pain animal models, particularly the relationship between changes in Kv channels and the excitability of trigeminal ganglion (TRG) neurons. We also discuss the potential of Kv channel openers as therapeutic agents for trigeminal neuropathic/inflammatory pain, such as mechanical allodynia

Sitagliptin and Carotid Atherosclerosis in Type 2 Diabetes

Background Experimental studies have suggested that dipeptidyl peptidase-4 (DPP-4) inhibitors provide cardiovascular protective effects. We performed a randomized study to evaluate the effects of sitagliptin added on to the conventional therapy compared with conventional therapy alone (diet, exercise, and/or drugs, except for incretin-related agents) on the intima-media thickness (IMT) of the carotid artery, a surrogate marker for the evaluation of atherosclerotic cardiovascular disease, in people with type 2 diabetes mellitus (T2DM). Methods and Findings We used a multicenter PROBE (prospective, randomized, open label, blinded endpoint) design. Individuals aged ≥30 y with T2DM (6.2% ≤ HbA1c < 9.4%) were randomly allocated to receive either sitagliptin (25 to 100 mg/d) or conventional therapy. Carotid ultrasound was performed at participating medical centers, and all parameters were measured in a core laboratory. Of the 463 enrolled participants with T2DM, 442 were included in the primary analysis (sitagliptin group, 222; conventional therapy group, 220). Estimated mean (± standard error) common carotid artery IMT at 24 mo of follow-up in the sitagliptin and conventional therapy groups was 0.827 ± 0.007 mm and 0.837 ± 0.007 mm, respectively, with a mean difference of −0.009 mm (97.2% CI −0.028 to 0.011, p = 0.309). HbA1c level at 24 mo was significantly lower with sitagliptin than with conventional therapy (6.56% ± 0.05% versus 6.72%± 0.05%, p = 0.008; group mean difference −0.159, 95% CI −0.278 to −0.041). Episodes of serious hypoglycemia were recorded only in the conventional therapy group, and the rate of other adverse events was not different between the two groups. As it was not a placebo-controlled trial and carotid IMT was measured as a surrogate marker of atherosclerosis, there were some limitations of interpretation. Conclusions In the PROLOGUE study, there was no evidence that treatment with sitagliptin had an additional effect on the progression of carotid IMT in participants with T2DM beyond that achieved with conventional treatment

Large Questionnaire Survey on Sleep Duration and Insomnia Using the TV Hybridcast System by Japan Broadcasting Corporation (NHK).

Background:Japanese people are known to have the shortest sleep duration in the world. To date, no study has assessed a large Japanese population for insomnia and sleep duration.Methods:We performed an Ιnternet-based survey in association with a national television (TV) program. Questionnaire data were collected not only through personal computers, tablets, and smartphones, but also through the Hybridcast system, which combines broadcasts over airwaves with broadband data provided via the Internet using the TV remote controller. The Athens Insomnia Scale (AIS) was used to assess insomnia.Results:A total of 301,241 subjects participated in the survey. Participants slept for an average of 5.96 ± 1.13 h; the average AIS score was 6.82 ± 3.69. A total of 26.1% of male and 27.1% of female participants had both insomnia (AIS ≥ 6) and short sleep duration (<6 h). Responses were recorded through the Hybridcast system for 76.4% of the elderly (age ≥ 65 years) subjects and through personal computers, tablets, or smartphones for 59.9–82.7% of the younger subjects (age ≤ 65 years).Conclusions:Almost a quarter of the Japanese participants presented short sleep duration and insomnia. Furthermore, the Hybridcast system may be useful for performing large internet-based surveys, especially for elderly individuals