Objective: The squeezing force and one-drop weight, suggested to directly influence adherence, were measured in 6 eye drop products containing a switch OTC drug, ketotifen fumarate, to investigate useful information for product selection.
Methods: The squeeze force, one drop weight, and pH were measured using a digital force gauge, analytical balance, and pH meter, respectively.  Information on additives contained in each product was collected from package inserts.  For the total number of drops, the number per 10 mL was calculated from the obtained value.
Results: The maximum squeeze force was 14.8 N of Irice AG Guard, and the one drop weight (33.2 mg) of Raferusa®AL was the minimum.  The total number of drops per 10 mL was 215 in Sutto eyes Z, being the minimum.  The pH was in the range of 5.2-5.7.  On comparison of additives among the products, a cooling agent was contained in only 2 products.
Discussion: Since the squeeze force was in the range of 5.3-14.8 N, it was less likely that the squeeze force reduces usability.  Since the one-drop weights of 2 products were more than 10 mg lower than the weights of the other products, the dose may be insufficient and the effect may not be attained.  The pH was within the acceptable range in all products.  Two products contain a cooling agent as an additive, and this has to be explained beforehand.  Information related to usability, actual feeling of the effect, and sense of the use of the products containing ketotifen fumarate was collected.

Guanylyl cyclase C (GC-C) is a member of a family of enzymes that metabolize GTP to cGMP and was first identified as a receptor for heat-stable enterotoxin. Guanylin (GNY) has since been identified as an endogenous ligand for GC-C in the intestine of several mammalian species. The GNY/GC-C system regulates ion transportation and pH in the mucosa. Recently, it was reported that GC-C and GNY are involved in lipid metabolism in rat mesenteric adipose tissue macrophages. To examine the role of GC-C and GNY in lipid metabolism in cattle, we used a bovine mesenteric adipocyte primary culture system and a coculture system for bovine adipocytes and GNY-/GC-C-expressing macrophages. Fat droplets were observed to accumulate in bovine mesenteric adipocytes cultured alone, whereas few fat droplets accumulated in adipocytes indirectly cocultured with macrophages. We also observed that GC-C was present in bovine mesenteric adipose tissue, and that fat droplet accumulation decreased after in vitro GNY administration. Expressions of mRNAs encoding lipogenic factors decreased significantly in adipocytes after either coculture or GNY administration. These results suggest that the GNY/GC-C system is part of the control system for lipid accumulation in bovine mesenteric adipose tissue.
Adipocytes ; Adipose Tissue* ; Animals ; Cattle* ; Coculture Techniques ; Enterotoxins ; Guanosine Triphosphate ; Guanylate Cyclase* ; Humans ; Hydrogen-Ion Concentration ; In Vitro Techniques ; Intestines ; Ion Transport ; Lipid Metabolism ; Macrophages ; Mucous Membrane ; Rats ; RNA, Messenger

Atlanto-occipital dislocation (AOD) is rarely seen in clinic because it is characteristically immediately fatal. With recent progress in the pre-hospital care, an increasing number of AOD survivors have been reported. However, because the pathophysiology of AOD is not clearly understood yet, the appropriate strategy for the initial management remains still unclear. We report a case of successful AOD treatment and describe important points in the management of this condition. It is important to note that abducens nerve palsy is a warning sign of AOD and that AOD can result in a life-threatening distortion of the arteries and the brain stem. We recommend the application of a halo vest to protect the patient's neural and vascular competence as the immediate initial step in the treatment of AOD. Horn's grading system is useful in assessing indications for surgery. Finally, when performing posterior fixation, C2 should be included because of the anatomy of the ligamentous architecture.
Abducens Nerve Diseases ; Arteries ; Atlanto-Occipital Joint ; Brain Stem ; Dislocations* ; External Fixators ; Humans ; Internal Fixators ; Ligaments ; Mental Competency ; Survivors

The purpose of this study is to evaluate the efficacy of hochuekkito for late-onset hypogonadism (LOH) patients. We administered hochuekkito 7.5 g/day for 8 weeks to 47 patients with LOH whose AMS scale was more than 27. We assessed the patients' symptom change with the AMS, SHIM, SDS, BDI, and SF-36. We measured their endocrine profiles and levels of their cytokines. At the end of study, 31 of 47 patients were evaluable. No significant difference in subjective symptoms was seen with any questionnaire after 8 weeks hochuekkito administration. However, hochuekkito significantly increased free testosterone and decreased ACTH/cortisol levels. Thus we believe hochuekkito is beneficial for the treatment of LOH.

The follicle-associated epithelium (FAE) of Peyer's patches (PPs) contains M cells that are important for reducing mucosal immune responses by transporting antigens into the underlying lymphoid tissue. We generated a monoclonal antibody (C6) that reacted with the FAE of calf ileal PPs, and analyzed the characteristics of C6 using immunohistochemistry and Western blotting. FAE of the ileal PP was stained with C6 during both late fetal developmental and postnatal stages. Neither the villous epithelial cell nor intestinal crypt basal cells were stained at any developmental stage. During the prenatal stages, FAE of the jejunal PP was C6-negative. However, a few C6-positive cells were distributed diffusely in some FAE of the jejunal PPs during the postnatal stages. The protein molecular weight of the antigen recognized by C6 was approximately 45 kDa. These data show that C6 is useful for identifying the FAE in ileal PPs and further suggest that differentiation of the FAE in these areas is independent of external antigens.
Animals ; Antibodies, Monoclonal/*immunology ; *Cattle ; Fetus ; Hybridomas ; Ileum/*ultrastructure ; Intestinal Mucosa/*immunology ; Peyer's Patches/*immunology/ultrastructure

The follicle-associated epithelium (FAE) of Peyer's patches (PPs) contains M cells that are important for reducing mucosal immune responses by transporting antigens into the underlying lymphoid tissue. We generated a monoclonal antibody (C6) that reacted with the FAE of calf ileal PPs, and analyzed the characteristics of C6 using immunohistochemistry and Western blotting. FAE of the ileal PP was stained with C6 during both late fetal developmental and postnatal stages. Neither the villous epithelial cell nor intestinal crypt basal cells were stained at any developmental stage. During the prenatal stages, FAE of the jejunal PP was C6-negative. However, a few C6-positive cells were distributed diffusely in some FAE of the jejunal PPs during the postnatal stages. The protein molecular weight of the antigen recognized by C6 was approximately 45 kDa. These data show that C6 is useful for identifying the FAE in ileal PPs and further suggest that differentiation of the FAE in these areas is independent of external antigens.
Animals ; Antibodies, Monoclonal/*immunology ; *Cattle ; Fetus ; Hybridomas ; Ileum/*ultrastructure ; Intestinal Mucosa/*immunology ; Peyer's Patches/*immunology/ultrastructure

Objective: In this study, pharmaceutical properties were compared between the original and generic ophthalmic solutions containing betamethasone.Methods: The squeeze force, drop weight, surface tension, pH, kinematic viscosity, and total number of drops were measured. The drop volume was calculated from the drop weight and specific gravity. Information on preservatives contained in each product was collected from package inserts.Results: There was a significant difference in the squeeze force between the original and generic drugs. The pH and kinematic viscosity did not differ between the drugs. The drop volume was in the range of 30.3 to 47.2 μL, and the surface tension ranged between 33.7 and 65.2 mN/N. The total number of drops was approximately 100 in the original drug, being the lowest.Conclusion: The results of this study showed that the squeeze forces of all generic products but RINBETA PF, which was contained in a specific container, were smaller than that of the original product. The drop volumes of 2 generic products were ≥ 15-μL smaller than that of the original product, but they were within the permissible range. The maximum difference in the surface tension was approximately 33 mN/N, suggesting that drug solution relatively frequently overflows from the eyes. The total number of drops for all generic products was greater than that for the original product, suggesting that the former can be used at a higher frequency. Based on these results, pharmacists must select products in accordance with individual patients.

Objective: Glaucoma is the most frequent cause of blindness in Japan and is primarily treated using IOP-lowering ophthalmic solutions. Although the patients themselves frequently instill ophthalmic solutions, instillation by caregivers may be necessary for various reasons. Therefore, we evaluated pharmaceutical characteristics of antiglaucoma ophthalmic solutions and their usability from the caregivers' viewpoint.Methods: Five dorzolamide hydrochloride-timolol maleate ophthalmic solutions and 2 travoprost-timolol maleate ophthalmic solutions were evaluated concerning the pharmaceutical characteristics and subjective squeezability rated by adults aged 20 years or above.Results: Among the dorzolamide hydrochloride-timolol maleate compounding ophthalmic solutions, the squeeze force was the lowest in COSOPT® ophthalmic solution (11.8 N), and DORMOLOL® combination ophthalmic solution NITTEN was rated highest, with 68.2% of the subjects placing it within the top 3 levels of a 7-level scale. Of the travoprost-timolol maleate ophthalmic solutions, the squeeze force was 9.8 N, lower than the pioneer drug, in TraTimo® combination ophthalmic solution NITTO, which was also rated in the top 3 levels by 90.3% of the subjects. A strong negative correlation was observed between the squeeze force and squeezability.Conclusion: In instillation by caregivers, the squeeze force was shown to be correlated with subjective squeezability as in instillation by patients themselves. This study provided information concerning the usability of ophthalmic solutions from the caregivers' viewpoint. For the future, it is necessary to select ophthalmic solutions from the caregivers' as well as the patients' viewpoints by utilizing information obtained in this study.

To smoothly proceed with the national policies and projects concerning dementia measures, it is important that pharmacists who take care of patient in clinical practice sufficiently understand its contents. In this study, we conducted a questionnaire survey involving chain community pharmacists to investigate the level of awareness concerning these policies and projects. Subjects were 446 chain community pharmacists. The questionnaire consisted of 17 items (e.g. the level of awareness regarding the “Comprehensive Strategy to Accelerate Dementia Measures (New Orange Plan)”, “Dementia Supporters Caravan Program (Caravan Program)”, and “Dementia training certified pharmacist program (Certification program)”). The questionnaires were filled out anonymously. The levels of awareness concerning the “New Orange Plan” and “Caravan Program” were 34.7% and 48.9%, respectively. Sixty-one percent of subjects attended a “Dementia Supporter Training Lecture”, 30.4% of whom were wearing the “orange ring”. The levels of awareness and the hope of acquisition concerning the “Certification program” were 47.8% and 79.8%, respectively. To achieve the purpose of “contribution to early detection of dementia by pharmacist” of the “New Orange Plan”, it is necessary to conducting the workshop and to create an opportunity to come in contact with dementia patients. It is also important to recognize that it is necessary to enlighten the meaning of wearing an “orange ring” and to enlarge the circle of dementia supporters. In addition, it is thought that more dementia patients can be supported in the community by increasing the levels of awareness concerning the “Certification program” and giving appropriate advice and response.

Background/Aims: Pathological evaluation is crucial for diagnosing biliary lesions and determining appropriate treatment strategies. However, tissue sampling via the transpapillary route can be difficult. In this study, we aimed to assess the efficacy and safety of a novel tapered-tip sheath system for tissue sampling from biliary strictures. Methods: This single-center, randomized, parallel-group clinical trial included patients aged 20 to 85 years admitted to Kyoto University Hospital for biliary strictures. The patients were randomly assigned (1:1) to a new or conventional method group. The primary outcome was technical success of biopsy at the target bile duct using the assigned method, as determined in accordance with the intention-to-treat principle. Adverse events were assessed in all eligible patients. Results: Fifty-six patients were assessed for eligibility between September 2020 and March 2023; 50 patients were enrolled. The patients were randomly divided into the new (n=25) method group and the conventional (n=25) method group. Technical success was achieved in 96.0% (24/25) and 48.0% (12/25) of patients in the new and conventional method groups, respectively (risk ratio, 2.00; 95% confidence interval [CI], 1.32 to 3.03; risk difference, 48.0%; 95% CI, 27.0% to 69.0%; p<0.001). Adverse events occurred in 4.0% (1/25) and 36.0% (9/25) of patients in the new and conventional method groups, respectively (risk ratio, 0.11; 95% CI, 0.02 to 0.81; risk difference, –32.0%; 95% CI, –52.3% to –11.7%; p=0.005). Conclusions The novel tapered-tip sheath system is a promising option for precisely and safely delivering biopsy forceps to target sites, thereby facilitating the diagnosis of biliary strictures.