A Novel Hemostatic Peptide Solution for Common Acute Gastrointestinal Bleeding Diseases: First Case Series Study on the Treatment Results of Endoscopic Hemostasis by Nonexpert Endoscopists.

INTRODUCTION: We investigated the hemostatic effect and safety of a hemostatic peptide solution for the treatment of gastrointestinal bleeding requiring emergency endoscopy. METHODS: We retrospectively examined the patient backgrounds, hemostatic results, and procedural safety in patients who were treated with a hemostatic peptide solution for hemostasis during emergency endoscopies for gastrointestinal bleeding. All hemostatic procedures were performed by nonexpert physicians with less than 10 years of endoscopic experience. All of the cases were treated at a single institution over the months from January 2022 to January 2023. RESULTS: Twenty-six consecutive patients (17 males and 9 females) with a median age of 74 (45-95) years were included. Their conditions requiring emergency endoscopy were melena in 8 patients, hematochezia in 2, hematemesis in 8, anemia in 6, and bleeding during esophagogastroduodenoscopy in 2. The sites of bleeding were the esophagus in 3 patients, the stomach in 17, the duodenum in 3, the small intestine in 2, and the colon in 1. Hemostasis was obtained with another hemostasis device used in conjunction with the hemostatic peptide solution in 13 cases and with the hemostatic peptide solution alone in 13 cases. The hemostasis success rate was 100%, with no complications. Rebleeding occurred within 1 week in 4 cases. CONCLUSION: Hemostasis with the hemostatic peptide solution was safe and provided a temporary high hemostatic effect in emergency gastrointestinal endoscopy.

[Epstein-Barr virus-associated gastritis with perigastric lymphadenopathy accompanied by infectious mononucleosis:a case report].

A 28-year-old female patient with no particular medical history had a sore throat seven days before admission. Subsequently, she developed malaise, right abdominal pain, and a fever of 38°C and visited our hospital. A blood test revealed a mild inflammatory response and elevated liver enzymes, and she was admitted to the hospital for detailed examination and acute liver injury treatment. Various viral tests and autoantibody measurements revealed elevated Epstein-Barr virus (EBV) immunoglobulin M and negative EB nuclear antigen antibodies. Therefore, she was diagnosed with primary infectious mononucleosis-associated EB viral hepatitis. Abdominal computed tomography upon admission revealed swollen lymph nodes around the stomach;thus, esophagogastroduodenoscopy (EGD) was performed. A histopathological examination revealed severe lymphocytic infiltration, and EB encoding region in situ hybridization demonstrated that 10-20% of the lymphocytes were EBV-infected. Drip and rest treatment improved the patient's liver enzymes, and her symptoms resolved. Repeat EGD after two months revealed improved gastric erosions. Here, we report a case of EBV-associated gastritis that was discovered due to perigastric lymphadenopathy accompanied by infectious mononucleosis. This report includes a review of the literature because a few studies reported EBV-associated gastritis.

Oral administration of whole dihomo-γ-linolenic acid-producing yeast suppresses allergic contact dermatitis in mice.

Dihomo-γ-linolenic acid (DGLA, C20: 3n-6) is known to have an anti-inflammatory activity, but its range of effects was not well studied because of its limited natural sources. We addressed these issues by constructing an yeast Saccharomyces cerevisiae strain having a complete metabolic pathway for DGLA synthesis by introducing two desaturase and one elongase genes to convert endogenous oleic acid to DGLA. Taking advantage of well-known safety of S. cerevisiae, we previously investigated the efficacy of heat-killed whole DGLA-producing yeast cells on irritant contact dermatitis, and showed that oral intake of this yeast significantly suppressed inflammatory reactions, whereas no such suppression was observed by the intake of 25 times the amount of purified DGLA. Since this method is considered to be a simple and efficient way to suppress inflammation, we examined its effectiveness against allergic contact dermatitis (ACD) in this study and showed that this method was also effective against ACD.

Effects of forefoot arthroplasty on plantar pressure, pain, gait and disability in rheumatoid arthritis.

Objectives: The purpose of this study was to clarify the effect of forefoot arthroplasty on plantar pressure, pain, gait, and disability within 1 year after arthroplasty in patients with RA.Methods: Eleven patients with RA who underwent forefoot arthroplasty completed this quasi-experimental study. Outcome measures were in-shoe plantar pressure, visual analog scale (VAS) for pain, temporal gait parameters, and modified Health Assessment Questionnaire (mHAQ), obtained preoperatively and at 4 and 12 months postoperatively.Results: The average peak plantar pressure under the 2nd metatarsal head decreased at 4 months postoperatively, compared to preoperative values (p < .05) and the decreased plantar pressure was sustained at 12 months postoperatively. Similar changes were observed under the 3rd to 5th metatarsal heads. The median VAS for foot pain decreased from 25 mm preoperatively to 1 mm at 4 months postoperatively and the lower score was sustained at 12 months postoperatively (p < .05). The median mHAQ score remained lower (<1.0) at all measurement points. Regarding gait, there were no significant differences from the preoperative assessment to postoperative follow-up.Conclusion: Plantar pressure and forefoot pain decreased at 4 and 12 months after forefoot arthroplasty in patients with RA. No adverse effects on gait parameters or disability were observed.

Effects of solid-liquid separation and storage on monensin attenuation in dairy waste management systems.

Environmental release of veterinary pharmaceuticals has been of regulatory concern for more than a decade. Monensin is a feed additive antibiotic that is prevalent throughout the dairy industry and is excreted in dairy waste. This study investigates the potential of dairy waste management practices to alter the amount of monensin available for release into the environment. Analysis of wastewater and groundwater from two dairy farms in California consistently concluded that monensin is most present in lagoon water and groundwater downgradient of lagoons. Since the lagoons represent a direct source of monensin to groundwater, the effect of waste management, by mechanical screen separation and lagoon aeration, on aqueous monensin concentration was investigated through construction of lagoon microcosms. The results indicate that monensin attenuation is not improved by increased solid-liquid separation prior to storage in lagoons, as monensin is rapidly desorbed after dilution with water. Monensin is also shown to be easily degraded in lagoon microcosms receiving aeration, but is relatively stable and available for leaching under typical anaerobic lagoon conditions.

Atg8 is involved in endosomal and phagosomal acidification in the parasitic protist Entamoeba histolytica.

Autophagy is one of two major bulk protein degradation systems and is conserved throughout eukaryotes. The protozoan Entamoeba histolytica, which is a human intestinal parasite, possesses a restricted set of autophagy-related (Atg) proteins compared with other eukaryotes and thus represents a suitable model organism for studying the minimal essential components and ancestral functions of autophagy. E. histolytica possesses two conjugation systems: Atg8 and Atg5/12, although a gene encoding Atg12 is missing in the genome. Atg8 is considered to be the central and authentic marker of autophagosomes, but recent studies have demonstrated that Atg8 is not exclusively involved in autophagy per se, but other fundamental mechanisms of vesicular traffic. To investigate this question in E. histolytica, we studied on Atg8 during the proliferative stage. Atg8 was constitutively expressed in both laboratory-maintained and recently established clinical isolates and appeared to be lipid-modified in logarithmic growth phase, suggesting a role of Atg8 in non-stress and proliferative conditions. These findings are in contrast to those for Entamoeba invadens, in which autophagy is markedly induced during an early phase of differentiation from the trophozoite into the cyst. The repression of Atg8 gene expression in En. histolytica by antisense small RNA-mediated transcriptional gene silencing resulted in growth retardation, delayed endocytosis and reduced acidification of endosomes and phagosomes. Taken together, these results suggest that Atg8 and the Atg8 conjugation pathway have some roles in the biogenesis of endosomes and phagosomes in this primitive eukaryote.

Development of the Larval Amphibian Growth and Development Assay: Effects of benzophenone-2 exposure in Xenopus laevis from embryo to juvenile.

The Larval Amphibian Growth and Development Assay (LAGDA) is a globally harmonized chemical testing guideline developed by the U.S. Environmental Protection Agency in collaboration with Japan's Ministry of Environment to support risk assessment. The assay is employed as a higher tiered approach to evaluate effects of chronic chemical exposure throughout multiple life stages in a model amphibian species, Xenopus laevis. To evaluate the utility of the initial LAGDA design, the assay was performed using a mixed mode of action endocrine disrupting chemical, benzophenone-2 (BP-2). X. laevis embryos were exposed in flow-through conditions to 0, 1.5, 3.0 or 6.0 mg l-1 BP-2 until 2 months post-metamorphosis. Overt toxicity was evident throughout the exposure period in the 6.0 mg l-1 treatment due to elevated mortality rates and observed liver and kidney pathologies. Concentration-dependent increases in severity of thyroid follicular cell hypertrophy and hyperplasia occurred in larval tadpoles indicating BP-2-induced impacts on the thyroid axis. Additionally, gonads were impacted in all treatments with some genetic males showing both testis and ovary tissues (1.5 mg l-1 ) and 100% of the genetic males in the 3.0 and 6.0 mg l-1 treatments experiencing complete male-to-female sex reversal. Concentration-dependent vitellogenin induction occurred in both genders with associated accumulations of protein in the livers, kidneys and gonads, which was likely vitellogenin and other estrogen-responsive yolk proteins. This is the first study that demonstrates the endocrine effects of this mixed mode of action chemical in an amphibian species and demonstrates the utility of the LAGDA design for supporting chemical risk assessment. Copyright © 2016 John Wiley & Sons, Ltd.

Fecal Indicator and Pathogenic Bacteria and Their Antibiotic Resistance in Alluvial Groundwater of an Irrigated Agricultural Region with Dairies.

Surveys of microbiological groundwater quality were conducted in a region with intensive animal agriculture in California, USA. The survey included monitoring and domestic wells in eight concentrated animal feeding operations (CAFOs) and 200 small (domestic and community supply district) supply wells across the region. was not detected in groundwater, whereas O157:H7 and were each detected in 2 of 190 CAFO monitoring well samples. Nonpathogenic generic and spp. were detected in 24.2% (46/190) and 97.4% (185/190) groundwater samples from CAFO monitoring wells and in 4.2% (1/24) and 87.5% (21/24) of CAFO domestic wells, respectively. Concentrations of both generic and spp. were significantly associated with well depth, season, and the type of adjacent land use in the CAFO. No pathogenic bacteria were detected in groundwater from 200 small supply wells in the extended survey. However, 4.5 to 10.3% groundwater samples were positive for generic and . Concentrations of generic were not significantly associated with any factors, but concentrations of were significantly associated with proximity to CAFOs, seasons, and concentrations of potassium in water. Among a subset of and isolates from both surveys, the majority of (63.6%) and (86.1%) isolates exhibited resistance to multiple (≥3) antibiotics. Findings confirm significant microbial and antibiotic resistance loading to CAFO groundwater. Results also demonstrate significant attenuative capacity of the unconfined alluvial aquifer system with respect to microbial transport.

Increased serum mitochondrial creatine kinase activity as a risk for hepatocarcinogenesis in chronic hepatitis C patients.

Serum mitochondrial creatine kinase (MtCK) activity was reportedly increased in cirrhotic patients although less prominent than that in hepatocellular carcinoma (HCC) patients. To elucidate the clinical significance of serum MtCK activity in chronic liver disease, 171 chronic hepatitis C patients were enrolled. Serum MtCK activity in study subjects was correlated with serum albumin, platelet counts, liver stiffness values and serum aspartate and alanine aminotransferase. In mouse fibrotic liver induced by bile duct ligation, ubiquitous MtCK mRNA and protein expressions were significantly enhanced and its immunoreactivity was increased, predominantly in hepatocytes. During the mean follow-up period of 2.7 years, HCC developed in 21 patients, in whom serum MtCK activity was significantly higher than that in patients without HCC development. Multivariate Cox regression analysis revealed that higher serum MtCK activity was a risk for HCC development. A cutoff value of MtCK for the prediction of HCC development was determined as 9.0 U/L on receiver operating characteristics analysis, where area under receiver operating characteristics curve was 0.754, with a sensitivity of 61.9%, a specificity of 92.8% and a high negative predictive value of 94.2%. Cumulative incidence of HCC was significantly higher in patients with serum MtCK activity of >9.0 U/L compared to those with serum MtCK activity of ≤ 9.0 U/L even in patients with elevated liver stiffness value, >15 kPa. In conclusion, serum MtCK activity may be increased correlatively with the stage of liver fibrosis and hepatocellular damage. Increased serum MtCK activity is an independent risk for hepatocarcinogenesis in chronic hepatitis C patients.

The reproductive hormone cycle of adult female American alligators from a barrier island population.

Comparatively, little data are available detailing the geographic variation that exists in the reproductive endocrinology of adult alligators, especially those living in barrier islands. The Merritt Island National Wildlife Refuge (MI) is a unique barrier island environment and home to the Kennedy Space Center (FL, USA). Seasonal patterns of sex steroids were assessed in adult female American alligators from MI monthly from 2008 to 2009, with additional samples collected at more random intervals in 2006, 2007, and 2010. Plasma 17ß-estradiol and vitellogenin concentrations peaked in April, coincident with courtship and mating, and showed patterns similar to those observed in adult female alligators in other regions. Plasma concentrations of progesterone, however, showed patterns distinctly different than those reported for alligator populations in other regions and remained relatively constant throughout the year. Plasma DHEA peaked in July around the time of oviposition, decreased in August, and then remained constant for the remaining months, except for a moderate increase in October. Circulating concentrations of DHEA have not been previously assessed in a female crocodilian, and plasma concentrations coincident with reproductive activity suggest a reproductive and/or behavioral role. Interestingly, plasma testosterone concentrations peaked in May of 2008, as has been shown in female alligator populations in other regions, but showed no peak in 2009, demonstrating dramatic variability from year to year. Surveys showed 2009 to be particularly depauperate of alligator nests in MI, and it is possible that testosterone could serve as a strong indicator of breeding success.

Oral administration of whole dihomo-γ-linolenic acid-producing Saccharomyces cerevisiae suppresses cutaneous inflammatory responses induced by croton oil application in mice.

Polyunsaturated fatty acids have been attracting considerable interest because of their many biological activities and important roles in human health and nutrition. Dihomo-γ-linolenic acid (DGLA; C20: 3n-6) is known to have an anti-inflammatory activity, but its range of effects was not well studied because of its limited natural sources. Taking advantage of genetic tractability and increasing wealth of accessible data of Saccharomyces cerevisiae, we have previously constructed a DGLA-producing yeast strain by introducing two types of desaturase and one elongase genes to convert endogenous oleic acid (C18:1n-9) to DGLA. In this study, we investigated the efficacy of oral intake of heat-killed whole DGLA-producing yeast cells in the absence of lipid purification on cutaneous inflammation. Topical application of croton oil to mouse ears induces ear swelling in parallel with the increased production of chemokines and accumulation of infiltrating cells into the skin sites. These inflammatory reactions were significantly suppressed in a dose-dependent manner by oral intake of the DGLA-producing yeast cells for only 7 days. This suppression was not observed by the intake of the γ-linolenic acid-producing (C18:3n-6, an immediate precursor of DGLA) yeast, indicating DGLA itself suppressed the inflammation. Further analysis demonstrated that DGLA exerted an anti-inflammatory effect via prostaglandin E1 formation because naproxen, a cyclooxygenase inhibitor, attenuated the suppression. Since 25-fold of purified DGLA compared with that provided as a form of yeast was not effective, oral administration of the whole DGLA-producing yeast is considered to be a simple but efficient method to suppress inflammatory responses.

The molecular basis of myeloid malignancies.

Myeloid malignancies consist of acute myeloid leukemia (AML), myelodysplastic syndromes (MDS) and myeloproliferative neoplasm (MPN). The latter two diseases have preleukemic features and frequently evolve to AML. As with solid tumors, multiple mutations are required for leukemogenesis. A decade ago, these gene alterations were subdivided into two categories: class I mutations stimulating cell growth or inhibiting apoptosis; and class II mutations that hamper differentiation of hematopoietic cells. In mouse models, class I mutations such as the Bcr-Abl fusion kinase induce MPN by themselves and some class II mutations such as Runx1 mutations induce MDS. Combinations of class I and class II mutations induce AML in a variety of mouse models. Thus, it was postulated that hematopoietic cells whose differentiation is blocked by class II mutations would autonomously proliferate with class I mutations leading to the development of leukemia. Recent progress in high-speed sequencing has enabled efficient identification of novel mutations in a variety of molecules including epigenetic factors, splicing factors, signaling molecules and proteins in the cohesin complex; most of these are not categorized as either class I or class II mutations. The functional consequences of these mutations are now being extensively investigated. In this article, we will review the molecular basis of hematological malignancies, focusing on mouse models and the interfaces between these models and clinical findings, and revisit the classical class I/II hypothesis.

Antibiotic-resistant E. coli in surface water and groundwater in dairy operations in Northern California.

Generic Escherichia coli was isolated from surface water and groundwater samples from two dairies in Northern California and tested for susceptibility to antibiotics. Surface samples were collected from flush water, lagoon water, and manure solids, and groundwater samples were collected from monitoring wells. Although E. coli was ubiquitous in surface samples with concentrations ranging from several hundred thousand to over a million colony-forming units per 100 mL of surface water or per gram of surface solids, groundwater under the influence of these high surface microbial loadings had substantially fewer bacteria (3- to 7-log10 reduction). Among 80 isolates of E. coli tested, 34 (42.5%) were resistant to one or more antibiotics and 22 (27.5%) were multi-antibiotic resistant (resistant to ≥3 antibiotics), with resistance to tetracycline, cefoxitin, amoxicillin/clavulanic acid, and ampicillin being the most common. E. coli isolates from the calf hutch area exhibited the highest levels of multi-antibiotic resistance, much higher than isolates in surface soil solids from heifer and cow pens, flush alleys, manure storage lagoons, and irrigated fields. Among E. coli isolates from four groundwater samples, only one sample exhibited resistance to ceftriaxone, chloramphenicol, and tetracycline, indicating the potential of groundwater contamination with antibiotic-resistant bacteria from dairy operations.

Impact of body surface area on efficacy and safety in patients with EGFR-mutant non-small cell lung cancer treated with osimertinib as a first-line treatment.

BACKGROUND: The most recommended treatment for stage IV EGFR-positive lung cancer is osimertinib monotherapy. The dosage of osimertinib is fixed at 80 mg/day regardless of body surface area (BSA), however some patients withdraw or reduce the dosage due to adverse events (AEs). METHODS: We performed a retrospective cohort study of 98 patients with EGFR mutation-positive non-small cell lung cancer (NSCLC), who received 80 mg osimertinib as the initial treatment. We investigated the impact of BSA on efficacy and safety of osimertinib. RESULTS: The cut-off value of BSA was estimated using the receiver operating characteristics curve, and was determined to be 1.5 m2. There were 44 patients in the BSA < 1.5 group and 54 patients in the BSA ≥ 1.5 group. There was no significant difference in the incidence of AEs (hematologic toxicity of ≥grade 3 or higher, and non-hematologic toxicity of ≥grade 3) between the two groups. However, the incidence of dose reduction due to AEs was significantly higher in the BSA < 1.5 group compared with the BSA ≥ 1.5 group (16 patients vs 5 patients, p = 0.003). The main reasons were fatigue, anorexia, diarrhea, and liver disfunction. Median progression-free survival (PFS) was not significantly different (16.9 months in the BSA < 1.5 group vs 18.1 months in the BSA ≥ 1.5 group, p = 0.869). CONCLUSION: Differences in BSA affected the optimal dose of osimertinib. However, the PFS with osimertinib treatment was not affected by BSA. Therefore, when using osimertinib as an initial treatment for patients with EGFR-mutant NSCLC, dose reduction to control AEs should be considered, especially in the BSA<1.5 group.

Antagonism of sphingosine 1-phosphate receptor 2 causes a selective reduction of portal vein pressure in bile duct-ligated rodents.

UNLABELLED: Sinusoidal vasoconstriction, in which hepatic stellate cells operate as contractile machinery, has been suggested to play a pivotal role in the pathophysiology of portal hypertension. We investigated whether sphingosine 1-phosphate (S1P) stimulates contractility of those cells and enhances portal vein pressure in isolated perfused rat livers with Rho activation by way of S1P receptor 2 (S1P(2) ). Rho and its effector, Rho kinase, reportedly contribute to the pathophysiology of portal hypertension. Thus, a potential effect of S1P(2) antagonism on portal hypertension was examined. Intravenous infusion of the S1P(2) antagonist, JTE-013, at 1 mg/kg body weight reduced portal vein pressure by 24% without affecting mean arterial pressure in cirrhotic rats induced by bile duct ligation at 4 weeks after the operation, whereas the same amount of S1P(2) antagonist did not alter portal vein pressure and mean arterial pressure in control sham-operated rats. Rho kinase activity in the livers was enhanced in bile duct-ligated rats compared to sham-operated rats, and this enhanced Rho kinase activity in bile duct-ligated livers was reduced after infusion of the S1P(2) antagonist. S1P(2) messenger RNA (mRNA) expression, but not S1P(1) or S1P(3) , was increased in bile duct-ligated livers of rats and mice and also in culture-activated rat hepatic stellate cells. S1P(2) expression, determined in S1P 2LacZ/+ mice, was highly increased in hepatic stellate cells of bile duct-ligated livers. Furthermore, the increase of Rho kinase activity in bile duct-ligated livers was observed as early as 7 days after the operation in wildtype mice, but was less in S1P 2-/- mice. CONCLUSION: S1P may play an important role in the pathophysiology of portal hypertension with Rho kinase activation by way of S1P(2) . The S1P(2) antagonist merits consideration as a novel therapeutic agent for portal hypertension.

Stronger prognostic power of the CpG island methylator phenotype than methylation of individual genes in neuroblastomas.

OBJECTIVE: The CpG island methylator phenotype is strongly associated with poor survival in neuroblastomas. Neuroblastomas with the CpG island methylator phenotype include almost all neuroblastomas with MYCN amplification, and, even among neuroblastomas without MYCN amplification, have worse prognosis. At the same time, methylation of individual tumor-suppressor genes is also reported to be associated with poor survival. The purpose of this study was to compare the prognostic power of the CpG island methylator phenotype with that of methylation of individual genes. METHODS: Methylation-specific polymerase chain reaction was performed for five individual genes (CASP8, EMP3, HOXA9, NR1I2 and CD44) in 140 Japanese and 152 German neuroblastomas. Kaplan-Meier analysis and log-rank tests were conducted to compare the survival between groups defined by methylation status. RESULTS: Among the five individual genes, only CASP8 methylation had a significant association with poor overall survival both in Japanese (hazard ratio = 3.1; 95% confidence interval = 1.5-6.4; P = 0.002) and German (hazard ratio = 4.8; 95% confidence interval = 2.1-11; P = 0.0002) neuroblastomas. HOXA9 and NR1I2 methylation were associated with poor survival only in German neuroblastomas. On the other hand, the CpG island methylator phenotype had a strong and consistent association in Japanese (hazard ratio = 22; 95% confidence interval = 5.3-93; P = 1.5 × 10(-5)) and German (hazard ratio = 9.5; 95% confidence interval = 3.2-28; P = 4.7 × 10(-5)) neuroblastomas. CONCLUSION: The CpG island methylator phenotype is likely to have stronger prognostic power than methylation of individual genes in neuroblastomas.

Establishment of transactivation assay systems using fish, amphibian, reptilian and human thyroid hormone receptors.

Thyroid hormones are essential for the regulation of a wide range of biological processes associated with normal development and metabolism in vertebrates. For the screening of chemicals with a potential thyroid hormone and anti-thyroid hormone activities, we have established transient transactivation assay systems using thyroid hormone receptors (TRα and TRß) from three frog species (Xenopus laevis, Silurana tropicalis and Rana rugosa), a fish (Oryzias latipes), an alligator (Alligator mississippiensis) and a human (Homo sapiens). In all species examined, similar transcriptional activities were found for triiodothyronine (T3 : 10(-11) M in TRα and 10(-10) M in TRß) and thyroxine (T4 : 10(-9) M in TRα and 10(-8) M in TRß). Analogs of thyroid hormone (3,5,3',-triiodothyroacetic acid and 3,3',5,5'-tetraiodothyroacetic acid) exhibited weaker activity, requiring 10-fold higher concentrations for induction of activity when compared with T3 and T4 . These results provide support for the usefulness of in vitro screening assay systems as part of an approach to test chemicals for potential thyroid hormone receptor activity. In addition, we observed that T3 -stimulated transcriptional activity of the O. latipes TRα was inhibited by 10(-5) M tetrabromobisphenol A (TBBPA). In contrast, TR antagonist activities on TRα were not encountered in other species, even with TBBPA concentrations at 10(-5) M. In vitro transactivation assay systems using TRs from various species can be used for the screening of chemicals with thyroid-receptor agonist and antagonist activities. They also can be used for studies that examine evolutionary differences among species in the potency of TR activation.

Promotion of hair growth by Rosmarinus officinalis leaf extract.

Topical administration of Rosmarinus officinalis leaf extract (RO-ext, 2 mg/day/mouse) improved hair regrowth in C57BL/6NCrSlc mice that experienced hair regrowth interruption induced by testosterone treatment. In addition, RO-ext promoted hair growth in C3H/He mice that had their dorsal areas shaved. To investigate the antiandrogenic activity mechanism of RO-ext, we focused on inhibition of testosterone 5α-reductase, which is well recognized as one of the most effective strategies for the treatment of androgenic alopecia. RO-ext showed inhibitory activity of 82.4% and 94.6% at 200 and 500 µg/mL, respectively. As an active constituent of 5α-reductase inhibition, 12-methoxycarnosic acid was identified with activity-guided fractionation. In addition, the extract of R. officinalis and 12-methoxycarnosic acid inhibited androgen-dependent proliferation of LNCaP cells as 64.5% and 66.7% at 5 µg/mL and 5 µM, respectively. These results suggest that they inhibit the binding of dihydrotestosterone to androgen receptors. Consequently, RO-ext is a promising crude drug for hair growth.

Formulation and evaluation of matrix type mucoadhesive tablets aimed at treating oral aphtha.

CONTEXT: Nonsteroidal anti-inflammatory drugs (NSAIDs) are administered for pain relief from oral mucositis. However, the systemic administration of NSAIDs is limited due to the side effects of thrombocytopenia. OBJECTIVE: To avoid systemic side effects, a matrix type mucoadhesive tablet as a topical application preparation to treat oral aphtha was developed. METHODS: A mixture of hard fat with a low irritant property and mucoadhesive polymers was used as the matrix base, and indomethacin was used as a model drug. RESULTS: Among the water-soluble polymers, carbopol and xanthan gum increased the adhesive force of tablets prepared by the suspending method, but the tensile strength was not increased. Tablets containing ethylcellulose 10 or 45 (EC10, EC45) from a water-insoluble polymer increased the adhesive force and tensile strength. Tablets prepared by the dissolve-drying method containing EC45 showed a 1.8-fold increase of adhesiveness to the eggshell membrane compared with hard fat tablets, and showed a sustained release of the drug (17%) over an 8 h period. The drug release was increased to 28% by a modification to the dissolve-drying method using EC10. CONCLUSIONS: Since this matrix type tablet has long-acting properties, adhesiveness and low irritating properties, its potential as a newly designed preparation to treat oral aphtha is suggested.

Imaging findings of arrested pneumatisation and differentiation from other skull base lesions.

OBJECTIVES: Arrested pneumatisation (AP) is an anatomic variant of the sphenoid sinus. Since AP remains underrecognised, otolaryngologists and radiologists may mistake AP for a lesion and perform follow-up imaging studies. We investigated the imaging findings of CT, MRI, and F-18 fludeoxyglucose (FDG)-positron emission tomography (PET) for AP, and discussed the differences between AP and other skull base lesions. METHODS: We reviewed multidetector low CT imaging of 442 patients (285 men and 157 women; age range, 19-93 years; mean age, 67.8 years) who underwent FDG-PET/CT for head and neck tumours between January 2019 and December 2019. The imaging findings of AP were reviewed on CT, MRI, FDG-PET/CT, and compared with those of fibrous dysplasia, chordoma, chondrosarcoma, multiple myeloma, and bone invasion of nasopharyngeal carcinoma. RESULTS: AP was identified in 22 patients (14 men and 8 women; age range, 24-93 years; mean age, 67.0 years) based on criteria from previous reports. AP manifested with well-circumscribed sclerotic margins on CT, without evidence of expansion. AP showed high-signal intensity on T1-/T2 weighted MRI. FDG-PET revealed non-significant uptake [maximum standardised uptake value (SUVmax): 0.85 (range, 0.4-1.27)] in AP. Contrastingly, skull base lesions showed expansion, poorly circumscribed boundaries without osteosclerotic margins, and moderate-to-severe FDG uptake (SUVmax: 1.8-8.4). CONCLUSIONS: The characteristic imaging findings of AP, namely non-expansile on CT and non-uptake on FDG-PET, may aid in its differentiation from other skull base lesions.