[GABA(A) receptor trafficking and epilepsy].

Recent studies clarified a dynamic regulation of the intracellular trafficking of GABA(A) receptors and its involvement in the pathophysiology of epilepsy. GABA(A) synaptic inhibition decreased in the hippocampal CA1 area of patients with intractable temporal lobe epilepsy (TLE). The reduction of GABAergic inhibition was accompanied by a decrease in the expression of gephyrin, a scaffolding protein, and GABA(A) receptor gamma2 subunit. These findings indicate that the reduction of gephyrin impairs the clustering and fixation of GABA(A) receptors in postsynaptic membranes, leading to a decrease in number of GABA(A) receptor subunits and GABA(A) synaptic inhibition. In contrast, the GABA(A) synaptic inhibition was lastingly potentiated in the dentate gyrus of kindled animals and the expression of GABA(A) receptor subunits(especially alpha2) was significantly increased in TLE patients. It is plausible that the potentiation of dentate GABAergic inhibition counteracts a hyperexcitability of granule cells as a defense mechanism in epilepsy. In status epilepticus, furthermore, the hippocampal GABA(A) receptor beta3 subunits were significantly disphosphorylated, resulting in a facilitation of the endocytosis of GABA(A) receptors and reduced benzodiazepine sensitivity.

The Current Status of Utilizing a Medication Record Handbook for Evaluating Shared Medication History: A Retrospective Study Using the Japanese National Claims Database.

While the coronavirus disease 2019 (COVID-19) pandemic has impacted medication adherence and consultation patterns, its effects on the medical practice and dispensary separation system of Japan remain unclear. Thus, the utilization of the medication record handbook (MRH) in both medical and dental areas remains uncertain. This study uses the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB); we analyzed the separation of medication prescription and dispensing in both medicine and dentistry, as well as estimated how much drug information is shared by utilizing a patient-carried MRH. The external prescription (EP) rate was used as the main indicator. We then analyzed the MRH utilization rate during outpatient medication guidance. During the pandemic, there was no distinctive change in the rate of EPs in both medicine and dentistry. Furthermore, an analysis between EPs, medical internal prescriptions (IPs), and dental IPs relative to the MRH utilization rate revealed significant correlations between EPs and medical IPs as well as medical and dental IPs. Conversely, no significant correlation was found between EPs and dental IPs. Therefore, our results suggest that active MRH implementation within healthcare facilities may lead to an increase in its utilization in dentistry.

Feasibility of Child-Resistant and Senior-Friendly Press-Through Packages: Potential of Different Materials.

Press-through packaging (PTP) is the most common type of drug packaging in Japan, and a production procedure for PTP has been established at an acceptable cost. However, unknown problems and new needs with regard to safety among users of various age-groups still need to be examined. Considering accident reports involving children and older adults, the safety and quality of PTP and new forms of PTP, such as child-resistant and senior-friendly (CRSF) packaging, should be evaluated. We conducted an ergonomic study on children and older adults to compare types of commonly used PTP and new varieties of PTP. Opening tests were attempted by children and older adults using a common type of PTP (Type A) and child-resistant (CR) PTP (Types B1 and B2) made from soft aluminum foil. The same opening test was conducted on older patients with rheumatoid arthritis (RA). The results showed that CR PTP was difficult for children to open: only 1 out of 18 children could open Type B1. On the other hand, all eight of the older adults could open Type B1, and eight patients with RA could easily open Types B1 and B2. These findings suggest that the quality of CRSF PTP can be improved with the use of new materials.

Evaluation of Newly Designed Blister Packs for Easier Handling to Prevent Pill Dropping.

BACKGROUND: Blister packs with paperboard backing, which is useful for displaying instructions and information, are the most popular type of packaging for osteoporosis drugs in Japan. However, the main users of drugs are the aged, who often find blister packs difficult to open or drop their pills during opening. In this study, we compared different types of blister packs in terms of usability and handling. METHODS: We conducted a subjective and objective study to compare commonly used blister packs with newly designed ones that have a jagged notch designed to hold a pill temporarily and a perforated line that enables the pack to be held easily in one hand. Regarding subjective data, packaging and sensory tests were performed. The participants in the sensory test were healthy older adults and patients with rheumatoid arthritis (RA). We also measured the pinch power of all participants. RESULTS: A comparison of several items, including opening status, prevention of pill dropping, and understanding of the instructions, using a numerical rating scale revealed no significant differences between ordinary (type A) and newly designed (type B) packaging. However, the scores for type B were the same or better than those for type A for every evaluation item. In addition, more than 85% of the participants reported preferring to use type B. More than 80% of the participants in both groups reported dropping pills using type A, which seemed to be related to their preference for type B. In the evaluation by the examiner (objective study), all participants could successfully remove their pills without dropping using type B, including those in the RA group who had difficulty handling packages. CONCLUSION: These findings suggest that the new type of blister pack assessed in this study (type B) is preferable among older and shows promise for a universal design.

The angiotensin II type I receptor antagonist losartan retards amygdala kindling-induced epileptogenesis.

Blood-brain barrier (BBB) breakdown and the subsequent exposure of the cerebral cortex to serum albumin are known to activate transforming growth factor ß (TGF-ß) signaling in astrocytes and to play key roles in epileptogenesis after brain injury. It was recently reported that the angiotensin II type I receptor antagonist losartan suppresses activation of TGF-ß signaling and prevents epileptogenesis in a rat vascular injury model. Here, we investigated the effects of losartan on epileptogenesis following amygdala kindling in rats. Systemic or intracerebroventricular (i.c.v.) administration of losartan significantly delayed the development of severe behavioral seizures and stimulus-induced seizures on EEG (afterdischarge) in the early stage of amygdala kindling, as assessed by electroencephalography. Losartan also significantly increased the number of stimulations required to reach the fully kindled state. However, losartan had no effects on the threshold for afterdischarge induction, the afterdischarge duration, or seizure severity in fully kindled rats. Evaluation of BBB permeability by Evans blue staining did not indicate BBB breakdown (extravasation of serum albumin) in any region of the brain in the fully kindled animals. Thus, losartan may be useful in preventing epileptogenesis, even in post brain-insult epilepsy, in the absence of BBB breakdown.

Vagus nerve stimulation induced long-lasting enhancement of synaptic transmission and decreased granule cell discharge in the hippocampal dentate gyrus of urethane-anesthetized rats.

Vagus nerve stimulation (VNS) ameliorates deficits of hippocampal functions, such as contextual learning and memory, probably through direct modulation of neuronal activity. Previous studies showed that VNS enhanced excitatory synaptic transmission in the hippocampal CA3 area via activation of ß-adrenergic receptors. However, effects of VNS on excitatory synaptic transmission and action potential (AP) discharge of granule cells (GCs) in the dentate gyrus have not been studied. Urethane-anesthetized rats were used to investigate whether VNS influences synaptic transmission efficacy at perforant path-GC synapses and population spike discharge in the dentate gyrus. Intermittent burst stimulation of the left vagus nerve (30Hz for 30s at an inter-train interval of 5min for 1h) significantly enhanced the perforant path-GC synaptic transmission efficacy in the dentate gyrus for at least 2h, indicating that VNS can induce a long-lasting enhancement of synaptic transmission in this area, similar to the situation observed in the CA3 area. In contrast, a 60-min period of VNS significantly reduced population spike amplitude (a parameter reflecting synchronized AP discharge of GCs) for a given excitatory postsynaptic potential. These findings suggest that acute VNS enhances the excitatory synaptic transmission and reduces synchronized AP discharge of GCs in the dentate gyrus. It is likely that enhancement of excitatory synaptic transmission and reduction of GC excitability contribute VNS treatment efficacy for learning deficits and intractable epilepsy, respectively.