Terahertz bandpass filter with Babinet complementary metamaterial mirrors and silicon subwavelength structure.

We fabricated a rigid bandpass filter with a broad far-infrared wavelength range of high transmission using a silicon subwavelength structure with a Babinet complementary metamaterial half-mirror pair, despite its apparent light-blocking structure. The rigid one-piece filter was produced by a simple process involving photolithography, dry etching, and deposition, each performed only once. The transmission principle relies on the Fabry-Perot resonance with a metamaterial half-mirror pair that exhibits extraordinary optical transmission due to spoof surface plasmon polaritons. The transmission center wavelength was successfully predicted by the basic equation of Fabry-Perot resonance with an effective medium approximation. In contrast, a narrower bandwidth and a lower minimum transmittance than those predicted from the basic equation were provided by the subwavelength Si structure between the metamaterial mirrors, resulting in enhanced bandpass filter characteristics.

Use of machine learning with two-dimensional synthetic mammography for axillary lymph node metastasis prediction in breast cancer: a preliminary study.

Background: As of 2020, breast cancer is the most common type of cancer and the fifth most common cause of cancer-related deaths worldwide. The non-invasive prediction of axillary lymph node (ALN) metastasis using two-dimensional synthetic mammography (SM) generated from digital breast tomosynthesis (DBT) could help mitigate complications related to sentinel lymph node biopsy or dissection. Thus, this study aimed to investigate the possibility of predicting ALN metastasis using radiomic analysis of SM images. Methods: Seventy-seven patients diagnosed with breast cancer using full-field digital mammography (FFDM) and DBT were included in the study. Radiomic features were calculated using segmented mass lesions. The ALN prediction models were constructed based on a logistic regression model. Parameters such as the area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Results: The FFDM model yielded an AUC value of 0.738 [95% confidence interval (CI): 0.608-0.867], with sensitivity, specificity, PPV, and NPV of 0.826, 0.630, 0.488, and 0.894, respectively. The SM model yielded an AUC value of 0.742 (95% CI: 0.613-0.871), with sensitivity, specificity, PPV, and NPV of 0.783, 0.630, 0.474, and 0.871, respectively. No significant differences were observed between the two models. Conclusions: The ALN prediction model using radiomic features extracted from SM images demonstrated the possibility of enhancing the accuracy of diagnostic imaging when utilised together with traditional imaging techniques.

Surgery assistance system for continuous resection of brain tumors-proposal of continuous tumor resection forceps, tumor cell separation, dehydration, and isolation mechanism.

The tumor resection ratio must be improved due the increased possibility of recurrence or malignancy. The purpose of this study was to develop a system that includes forceps with a continuous suction function and flow cytometry to diagnose the malignancy of the tumor for safe, accurate, and effective surgery. A newly developed continuous tumor resection forceps consists of a triple pipe structure, which enables continuous suction of the tumor by integrating the reflux water and suction system. The forceps includes tip opening/closure detection switch to control the adsorption and suction strength when tip is opened and closed. To perform accurate tumor diagnosis using flow cytometry, a filtering mechanism was developed for dehydrating reflux water from continuous suction forceps. In addition, a cell isolation mechanism comprising a roller pump and shear force loading mechanism was also newly developed. By using a triple pipe structure, a significantly larger tumor collection ratio was observed compared to the previous double-pipe structure. By performing suction pressure control with the opening/closure detection switch, inaccurate suction can be prevented. By widening the filter area of dehydration mechanism, it was possible to improve the reflux water dehydration ratio. The most appropriate filter area was 85 mm2. By using a newly developed cell isolation mechanism, the processing time can be reduced to less than 1/10 of the original time, keeping the same cell isolation ratio, when compared to the existing pipetting method. Neurosurgery assistance system with continuous tumor resection forceps and a cell separation, dehydration and isolation mechanism was developed. An effective and safe tumor resection, accurate and fast diagnosis of malignancy can be achieved by using the current system.

Efficacy and safety of amrubicin therapy after chemoimmunotherapy in small cell lung cancer patients.

Background: Although the addition of immune checkpoint inhibitors (ICIs) to platinum-doublet chemotherapy has improved the efficacy of first-line therapy in extensive-disease small cell lung cancer (SCLC) patients, the best treatment option for patients with recurrent SCLC has not yet been determined. We conducted a retrospective study to evaluate the efficacy and safety of amrubicin (AMR) therapy after treatment with ICIs. Methods: We retrospectively assessed patients with recurrent SCLC who received AMR after chemoimmunotherapy at the Niigata Lung Cancer Treatment Group from August 2019 to February 2021. Results: This analysis included 30 patients. The median progression-free survival (PFS) and overall survival (OS) were 3.8 (95% CI: 2.7-4.2) and 10 (95% CI: 7.4-14.8) months, respectively. The median PFS and OS did not significantly differ between the sensitive and refractory groups [PFS; 3.1 (95% CI: 1.1-4.0) vs. 4.2 (95% CI: 2.3-4.8) months, P=0.1142, OS; 10.0 (95% CI: 5.2-14.8) vs. 10.4 (95% CI: 3.8-NE) months, P=0.5525]. The most common adverse event was grade ≥3 neutropenia, which occurred in 22 of 30 patients (73%), and 2 patients (7%) discontinued AMR due to adverse events. Conclusions: AMR after chemoimmunotherapy shows good clinical efficacy and safety in patients with recurrent SCLC.

Metabologenomic Approach Reveals Intestinal Environmental Features Associated with Barley-Induced Glucose Tolerance Improvements in Japanese: A Randomized Controlled Trial.

(1) Background: Consumption of barley has been known to exert beneficial effects on glucose tolerance; however, it has also been reported that there are inter-individual differences in these responses. Recent evidence has suggested that these individual differences are mediated by the gut microbiota. (2) Methods: In the present study, we aimed to understand the relationship between the intestinal environment, including intestinal microbiome and their metabolome, and glucose tolerance. A randomized controlled trial with a 4-week consumption of barley or control food was conducted. We conducted an integrated analysis of the intestinal microbiome and metabolome and analyzed the relationship with improvement of glucose tolerance. (3) Results: We found that metabolites such as azelate were significantly increased after barley consumption. Furthermore, the subjects whose glucose tolerance was slightly impaired showed improvement in their glucose tolerance index following the barley consumption. Additionally, the analysis showed that the increase in the abundance of the Anaerostipes was correlated with the improvement in the glucose tolerance index. (4) Conclusions: Our findings indicate that the effects of barley consumption for glucose tolerance are partly defined by the intestinal environment of consumers, providing a quantitative measurement of the dietary effect based on the intestinal environment.

Synthesis of Polynorbornadiene within the Pores of Activated Carbons: Effects on EDLC and Hydrogen Adsorption Performances.

Norbornadiene (NBD) is adsorbed on activated carbon (AC), and the adsorbed NBD is polymerized within the pores of AC. Two kinds of ACs─AC-2 with only micropores of ∼2 nm and AC-4 with not only micropores but also mesopores below 4 nm─are examined to study the effects of the hybridized polynorbornadiene (PNBD) on the electric double-layer capacitor and hydrogen adsorption performance. Various measurements are performed to determine the form of the hybridized PNBD inside the pores of AC. Scanning and transmittance electron microscopy observations of the AC/PNBD hybrids confirm that PNBD is hybridized inside the pores of AC, and there is little PNBD on the surface of AC particles. The nitrogen adsorption/desorption measurement for the hybrids of AC-4 reveals that PNBD is not hybridized preferentially inside micropores rather than mesopores irrespective of the amount of PNBD. In addition, both micropore and mesopore volumes decrease at a constant rate with increasing amounts of PNBD. These results suggest that PNBD is hybridized not as a layer but as an agglomerate for both ACs, and the agglomerate delocalizes over the whole AC pores, which is supported by the results of electrochemical measurements and hydrogen adsorption behavior of the hybrids.

Relationships between barley consumption and gut microbiome characteristics in a healthy Japanese population: a cross-sectional study.

BACKGROUND: Barley contains abundant soluble beta-glucan fibers, which have established health benefits. In addition, the health benefits conferred by the gut bacteria have attracted considerable interest. However, few studies have focused on the barley consumption and gut bacteria of the Japanese population. In this study, we aimed to identify the relationship between the barley consumption and gut bacteria composition of the Japanese population. METHODS: In total, 236 participants were recruited in Japan, and 94 participants with no complications of diabetes, hypertension, or dyslipidemia were selected for the study. We analyzed fecal samples from the participants, their medical check-up results, and responses to questionnaires about dietary habits. The participants were grouped according to their median barley consumption. Then, we assessed the relative abundance of 50 genera. Characteristic bacteria were evaluated for their relationship with barley consumption by multiple regression analysis, adjusted for disease and dietary habits, in all participants. We also analyzed the networks and clustering of the 20 selected genera. RESULTS: According to the comparison between barley groups, Bifidobacterium, Butyricicoccus, Collinsella, Ruminococcus 2, and Dialister were characteristic candidate bacterias of the group that consumed large amounts of barley (P < 0.05). The relationship between barley consumption and Bifidobacterium remained after adjusting for disease and dietary habits, and that of Butyricicoccus remained after adjusting for disease. Furthermore, network and cluster analyses revealed that barley consumption was directly correlated with Bifidobacterium and Butyricicoccus. CONCLUSIONS: Barley consumption generates changes in the intestinal bacteria of the Japanese population. We found that Bifidobacterium and Butyricicoccus abundance was positively associated with barley consumption.

Two-year administration of sodium-glucose co-transporter 2 inhibitor brought about marked reduction of body fat independent of skeletal muscle amount or glycemic improvement in Japanese patients with type 2 diabetes.

AIM: To investigate long-term effects of sodium-glucose co-transporter 2 inhibitor (SGLT2i) on anthropometric and metabolic factors in Japanese patients with type 2 diabetes (T2DM). PATIENTS AND METHODS: This is a retrospective observation study. Forty-six outpatients with T2DM (32 men and 14 women, 51 ± 13 years old, BMI 27.9 ± 4.8, means ± S.D.) who had been treated by SGLT2i for 2 years were selected and their metabolic and anthropometric data were retrieved from medical records retrospectively. Regular instruction for diet and exercise had been performed throughout the administration of SGLT2i in outpatient clinic basis. RESULTS: By the administration of SGLT2i for 2 years, body weight and body fat amount were significantly reduced (P < 0.0001) in spite of no change in skeletal muscle mass. HbA1c (P < 0.0001), liver function and lipid profile (P < 0.01) were ameliorated and eGFR was reduced significantly (P < 0.0001). It is of note that the reduction of body weight was strongly correlated to that of body fat (r = 0.951, P < 0.0001) with no correlation to the change of skeletal muscle mass. The reduction of HbA1c was strongly correlated to the baseline HbA1c (r = - 0.922, P < 0.0001) and modestly correlated to the baseline eGFR (r = - 0.449, P < 0.01). Multivariate analysis revealed a weak relationship between the amelioration of HbA1c and the reduction of body weight. CONCLUSION: SGLT2i can effectively reduce body weight and body fat mass independent of the blood glucose improvement or the renal function. Under the periodical instruction for nutrition and exercise this oral hypoglycemic agent can be safely administered for a long term without a risk for sarcopenia.

Phase II Trial of the Combination of Alectinib with Bevacizumab in Alectinib Refractory ALK-Positive Nonsquamous Non-Small-Cell Lung Cancer (NLCTG1501).

Anaplastic lymphoma kinase (ALK)-positive lung cancer is a rare cancer that occurs in approximately 5% of non-small-cell lung cancer (NSCLCs) patients. Despite the excellent efficacy of ALK-tyrosine kinase inhibitor in ALK-positive NSCLCs, most patients experience resistance. We conducted a phase II study to investigate the combination of alectinib with bevacizumab in ALK-positive NSCLC patients after failure of alectinib. In this study, ALK-positive nonsquamous NSCLC patients previously treated with alectinib received bevacizumab 15 mg/kg on day 1 every 3 weeks and alectinib 600 mg/day until disease progression. The primary endpoints were progression-free survival (PFS) and the safety of alectinib and bevacizumab. The secondary endpoints included overall survival (OS) and correlation of circulating tumor DNA and plasma proteins with PFS. Of the 12 patients treated, the median PFS was 3.1 months (95% CI 1.2-16.1), and the median OS was 24.1 months (95% CI 8.3-not estimable). The EML4-ALK fusion gene in circulating tumor DNA was significantly correlated with shorter PFS (1.2 months vs. 11.4 months, HR 5.2, p = 0.0153). Two patients experienced grade 3 adverse events; however, none of the patients required dose reduction. Although the primary endpoint was not met, alectinib combined with bevacizumab showed clinical efficacy in ALK-positive patients.

Distinct Roles for Dectin-1 and Dectin-2 in Skin Wound Healing and Neutrophilic Inflammatory Responses.

C-type lectin receptors recognize microbial polysaccharides. The C-type lectin receptors such as dendritic cell-associated C-type lectin (Dectin)-1 and Dectin-2, which are triggered by ß-glucan and α-mannan, respectively, contribute to upregulation of the inflammatory response. Recently, we demonstrated that activation of the Dectin-2 signal delayed wound healing; in previous studies, triggering the Dectin-1 signal promoted this response. However, the precise roles of these C-type lectin receptors in skin wound healing remain unclear. This study was conducted to determine the roles of Dectin-1 and Dectin-2 in skin wound healing, with a particular focus on the kinetics of neutrophilic inflammatory response. Full-thickness wounds were created on the backs of C57BL/6 mice, and the effects of Dectin-1 or Dectin-2 deficiency and those of ß-glucan or α-mannan administration were examined. We also analyzed wound closure, histological findings, and neutrophilic inflammatory response, including neutrophil extracellular trap formation at the wound sites. We found that Dectin-1 contributed to the acceleration of wound healing by inducing early-phase neutrophil accumulation, whereas Dectin-2 was involved in prolonged neutrophilic responses and neutrophil extracellular trap formation, leading to delayed wound healing. Dectin-2 deficiency also improved collagen deposition and TGF-ß1 expression. These results suggest that Dectin-1 and Dectin-2 have different roles in wound healing through their different effects on the neutrophilic response.

Masked Diabetes Insipidus Hidden by Severe Hyponatremia: A Case of Pituitary Metastasis of Lung Adenocarcinoma.

BACKGROUND Hyponatremia is an electrolyte disorder frequently encountered by clinicians. Secondary adrenal insufficiency due to pituitary metastatic tumors should be considered as an alternative diagnosis when clinicians encounter patients with lung cancer who demonstrate hyponatremia. However, masked central diabetes insipidus should also be considered to prevent critical dehydration when glucocorticoid replacement therapy will be initiated. CASE REPORT A 70-year-old man with advanced lung adenocarcinoma demonstrated high-grade hyponatremia of 122 mmol/L. Magnetic resonance imaging disclosed a metastatic pituitary tumor and endocrinological examinations confirmed panhypopituitarism, including secondary adrenal insufficiency. Hydrocortisone replacement revealed masked diabetes insipidus with elevation of serum sodium levels that reached 151 mmol/L. Desmopressin administration was required to prevent water depletion and to immediately ameliorate the hypernatremia. CONCLUSIONS This is the first case report of masked diabetes insipidus that demonstrated high-grade hyponatremia. Secondary adrenal insufficiency can mask the hypernatremia that is a typical manifestation of diabetes insipidus. Physicians should consider adrenal insufficiency and diabetes insipidus due to pituitary metastasis of advanced malignancies, even when they encounter patients with hyponatremia.

Pasireotide-induced hyperglycemia in a patient with Cushing's disease: Potential use of sodium-glucose cotransporter 2 inhibitor and glucagon-like peptide-1 receptor agonist for treatment.

Pasireotide improves hypercortisolemia and induces hyperglycemia via somatostatin receptor type-5 stimulation. GLP-1RA and SGLT2 inhibitor potentially help regulate hyperglycemia in patients with Cushing's disease, especially after pasireotide administration.

Pharmacist's Intervention Considering the Prognosis for a Terminal Cancer Patient: A Case Report.

Prognostic prediction has been reported to affect the decision of doctors and non-physician health care providers such as nurses, social workers, pastors, and hospice volunteers on the selection of appropriate medical interventions. This was a case of a 65-year-old woman who presented with a poor oral intake. The patient had a history of sigmoid colon cancer with abdominal wall metastasis and peritoneal dissemination. On the day of admission, nausea, anorexia, and malaise were noted, requiring immediate intervention. The patient's prognosis was predicted using the Palliative Prognostic Index. The pharmacist suggested the use of dexamethasone tablets in order to alleviate the patient's symptoms. Indeed, the administration of dexamethasone alleviated the symptoms of nausea, loss of appetite, and malaise. To the best of our knowledge, this is the first case report to demonstrate that prognosis prediction is important not only for other medical staff but also for pharmacists when deciding the need to initiate a treatment and continue such treatment, and when providing pharmacist interventions.

[Investigation of Clinical Utility of Radiological Technologist's Reading Report as a Second Opinion for Medical Doctor Reading of Digital Mammogram].

PURPOSE: We investigated the clinical utility of a radiological technologist's (RT)'s reports (RRs) as a second opinion by the free-response receiver operating characteristic (FROC) observer study that compared the performance of medical doctors' (MDs') reading of digital mammogram with and without consulting the RR. METHOD: One hundred women (39 malignant, 61 benign or normal) who underwent diagnostic mammography were selected from among 1674 routine clinical images classified by the degree of difficulty and categories for inclusion in the FROC study. The first FROC study performed by three RTs (RT 1-3) was conducted to collect the data for RR utilized in the second FROC study. The second FROC study was performed by five MDs, and the statistical significance of MDs' performances with and without reference to the RR was investigated by figure of merit (FOM). RESULT: The FOM values of three RTs obtained in the first FROC study were 0.529, 0.576, and 0.539, respectively. In the second FROC study, RT 2 had the highest FOM, RT 1 the lowest false positives/case, and RT 3 the highest sensitivity. The average FOM values in the second FROC study for the five MDs with/without reference to the RR were as follows: RT 2's RR was 0.534/0.588 (p=0.003), RT 1's RR was 0.500/0.545 (p=0.099), and RT 3's RR was 0.569/0.592 (p=0.324). CONCLUSION: We concluded that the MDs' performance of reading mammogram was statistically improved by consulting the RR when the RT's reading skill was high.

Improvement of skeletal muscle insulin sensitivity by 1 week of SGLT2 inhibitor use.

BACKGROUND AND AIMS: It is currently unclear whether sodium-glucose co-transporter 2 (SGLT2) inhibitor administration can improve the insulin sensitivity as well as rapidly reduce plasma glucose concentrations in humans during the early phase of treatment initiation. This study aimed to investigate the effect of SGLT2 inhibitor on insulin sensitivity in the early phase of treatment initiation. METHODS AND RESULTS: This single-center, open label, and single-arm prospective study recruited 20 patients (14 men) with type 2 diabetes mellitus (T2DM). We examined the patients' metabolic parameters before and 1 week after SGLT2 inhibitor (10 mg/day of empagliflozin) administration. The glucose infusion rate (GIR) was evaluated using the euglycemic hyperinsulinemic glucose clamp technique. Changes in laboratory and anthropometric parameters before and after SGLT2 inhibitor administration were analyzed according to the change in the GIR. The BMI, body fat amount, skeletal muscle amount, systolic blood pressure, and triglyceride level significantly decreased along with the treatment, while urinary glucose level and log GIR value significantly increased. Notably, changes in the GIR after SGLT2 inhibitor administration, which indicated improvement in peripheral insulin sensitivity, were negatively correlated with T2DM duration and positively with reduction in fluctuation of daily plasma glucose profiles before and after treatment. CONCLUSION: SGLT2 inhibitor improved insulin sensitivity in the skeletal muscle independent of anthropometric changes. Patients with short duration of T2DM and insulin resistance can be good candidates for short-term SGLT2 inhibitor administration to improve insulin sensitivity in the skeletal muscle.

Behavior of Japanese women after being informed about the benefits and disadvantages of breast cancer screening: a questionnaire survey.

BACKGROUND: The US Preventative Services Task Force assessed the efficacy of breast cancer screening according to the sum of its benefits and disadvantages. We estimate that the balance of the benefits and disadvantages varies among women depending on their demographic background. METHODS: Between March 2016 and March 2017, we conducted a questionnaire survey among Japanese women who underwent population-based or opportunistic breast cancer screening at our multicenter institutions. We investigated the behavior modification among women after being informed about the benefits and disadvantages of breast cancer screening depending on their demographic background. RESULTS: Out of 3032 questionnaires that were returned, 2936 (96.8%) were evaluated. The percentage of women with prior knowledge about the benefits and disadvantages of breast cancer screening before reading the leaflets that we created was 24%. However, 95% of the women were willing to undergo screening next time, despite knowing the disadvantages. Regarding overdiagnosis, the young women tended to choose usual treatment, and the elderly women tended to choose active surveillance. In response to the question on the significance of screening, the young women wished to avoid death by breast cancer; whereas, the elderly women wished to live a safe life. CONCLUSION: Our results indicate that the information of disadvantages does not lead to a reduction in screening rates. Additionally, we found that the balance between the benefits and disadvantages of breast cancer screening varies among women depending on their demographic background, especially age.

Metreleptin Supplementation for Improving Lipid and Glycemic Profiles in Acquired Diabetes Lipodystrophy: A Case Report.

Most childhood cancer survivors who undergo hematopoietic stem cell transplantation subsequently develop impaired glucose tolerance and hypertriglyceridemia. These conditions are presumably associated with total-body irradiation-related acquired lipodystrophy and may lead to cardiovascular disease. Metreleptin (recombinant leptin) may help improve the lipoprotein profile, insulin sensitivity, and quality of life of patients with total-body irradiation-related lipodystrophy. This report describes the safe and effective use of metreleptin supplementation for insulin resistance and dyslipidemia in acquired incomplete lipodystrophy. A 24-year-old Japanese woman with diabetes mellitus and hypertriglyceridemia was admitted to our hospital. She was diagnosed with acute lymphocytic leukemia at 3 years of age and had undergone systemic chemotherapy and total-body irradiation before allogeneic stem cell transplantation. She was also diagnosed with hypertriglyceridemia and diabetes mellitus at 11 years of age. She had a low adiponectin level, low-normal leptin level, and diabetes mellitus with marked insulin resistance. Thus, acquired incomplete lipodystrophy was diagnosed. Her serum triglyceride and lipoprotein profiles improved within 1 month of treatment initiation. Glycemic metabolism and insulin sensitivity in the skeletal muscles improved after 6 months. As previously reported, metreleptin therapy is effective in improving lipid and glycemic profiles in generalized lipodystrophy. In the present case, we considered that metreleptin supplementation could reduce the remnant VLDL cholesterol fraction and improve diabetes mellitus. We conclude that it may be an effective alternative therapy for improving the expected prognosis of patients with acquired incomplete lipodystrophy, including childhood cancer survivors.

Colonic fermentation of water soluble fiber fraction extracted from sugarcane (Sacchurum officinarum L.) bagasse in murine models.

Biochemical effects of the water soluble fiber fraction of sugarcane bagasse (BSF) fermented in the colon was examined to evaluate its potential health promoting effects. A feeding experiment involving Fischer 344 rats, was conducted with 3 experimental diets containing, cellulose (CON), a commercial xylo-oligosaccharide (XYO) and BSF (BGS). Cumulative feed intake was significantly lower in XYO group while cecal weight was significantly higher. Acetic and propionic acid contents in the cecal content were significantly higher in the BGS and XYO, respectively. Total short chain fatty acid content was significantly higher in BGS and XYO resulting significantly lower cecal pH. Beneficial bacteria such as Bifidobacterium, Blautia, Akkermansia and Roseburia abundance was significantly higher in the XYO and BGS groups. Further, mucin and immunoglobulin-A contents were significantly higher in BGS group compared to CON group. Thus, BSF exhibited its ability to enhance the intestinal and systemic health upon fermentation in the colon.

Solvatochromic Modeling of Laurdan for Multiple Polarity Analysis of Dihydrosphingomyelin Bilayer.

The hydration properties of the interface between lipid bilayers and bulk water are important for determining membrane characteristics. Here, the emission properties of a solvent-sensitive fluorescence probe, 6-lauroyl-2-dimethylamino naphthalene (Laurdan), were evaluated in lipid bilayer systems composed of the sphingolipids D-erythro-N-palmitoyl-sphingosylphosphorylcholine (PSM) and D-erythro-N-palmitoyl-dihydrosphingomyelin (DHPSM). The glycerophospholipids 1-palmitoyl-2-palmitoyl-sn-glycero-3-phosphocholine and 1-oleoyl-2-oleoyl-sn-glycero-3-phosphocholine were used as controls. The fluorescence properties of Laurdan in sphingolipid bilayers indicated multiple excited states according to the results obtained from the emission spectra, fluorescence anisotropy, and the center-of-mass spectra during the decay time. Deconvolution of the Laurdan emission spectra into four components based on the solvent model enabled us to identify the varieties of hydration and the configurational states derived from intermolecular hydrogen bonding in sphingolipids. Sphingolipids showed specific, interfacial hydration properties stemming from their intra- and intermolecular hydrogen bonds. Particularly, the Laurdan in DHPSM revealed more hydrated properties compared to PSM, even though DHPSM has a higher Tm than PSM. Because DHPSM forms hydrogen bonds with water molecules (in 2NH configurational functional groups), the interfacial region of the DHPSM bilayer was expected to be in a highly polar environment. The careful analysis of Laurdan emission spectra through the four-component deconvolution in this study provides important insights for understanding the multiple polarity in the lipid membrane.

Intracellular activation of trypsinogen in rat pancreatic acini after supramaximal secretagogue stimulation: cysteine protease and serine protease activity.

OBJECTIVE: The aim of the study was to explore the mechanism by which trypsinogen becomes activated during acute pancreatitis. METHODS: Given the ability of cholecystokinin (CCK) to induce pancreatitis in vivo, the effects of high-dose CCK on preparations of isolated pancreatic acini were examined using immunofluorescence techniques for the detection of trypsinogen activation. Acini were pretreated with weak base or serine or cysteine protease inhibitors before CCK hyperstimulation. RESULTS: CCK was found to stimulate the generation of trypsinogen activation peptide (TAP), a marker for trypsinogen processing. The generation of TAP was inhibited by pretreatment with a weak base, chloroquine (40 micromol/L). TAP generation was also inhibited by pretreatment with serine protease inhibitor FUT-175 (1 micromol/L) but not cysteine protease inhibitor E64 (0.1 mmol/L) or E64-d (0.1 mmol/L). Although treatment with a high dose of E64-d (1 mmol/L) reduced activation, it also caused cell injury. CONCLUSIONS: High-dose CCK stimulated the intracellular activation of trypsinogen within isolated pancreatic acini. This event appears to require an acidic subcellular compartment and serine protease activity. The role for thiol proteases in this model remains unclear.