Non-invasive detection of regulatory T cells with Raman spectroscopy.

Regulatory T cells (Tregs) are a type of lymphocyte that is key to maintaining immunological self-tolerance, with great potential for therapeutic applications. A long-standing challenge in the study of Tregs is that the only way they can be unambiguously identified is by using invasive intracellular markers. Practically, the purification of live Tregs is often compromised by other cell types since only surrogate surface markers can be used. We present here a non-invasive method based on Raman spectroscopy that can detect live unaltered Tregs by coupling optical detection with machine learning implemented with regularized logistic regression. We demonstrate the validity of this approach first on murine cells expressing a surface Foxp3 reporter, and then on peripheral blood human T cells. By including methods to account for sample purity, we could generate reliable models that can identify Tregs with an accuracy higher than 80%, which is already comparable with typical sorting purities achievable with standard methods that use proxy surface markers. We could also demonstrate that it is possible to reliably detect Tregs in fully independent donors that are not part of the model training, a key milestone for practical applications.

Direct comparison of anti-inflammatory effects of 14-, 15-, and 16-membered macrolide antibiotics in experimental inflammation model induced by carrageenan in rats.

Some macrolide antibiotics, which share a basic lactone ring structure, also exhibit anti-inflammatory actions in addition to their antibacterial activities. However, no study has directly compared anti-inflammatory effects on acute inflammation among macrolide antibiotics with the distinct size of the lactone ring. In this study, we evaluated and compared the anti-inflammatory activities of four 14-membered macrolides (erythromycin, clarithromycin, roxithromycin, oleandomycin), one 15-membered macrolide (azithromycin), and three 16-membered macrolides (midecamycin, josamycin, leucomycin) using a rat carrageenan-induced footpad edema model. All macrolide antibiotics were intraperitoneally administered to rats one hour before the induction of inflammatory edema with 1% λ -carrageenan. The anti-inflammatory effects on acute inflammation were evaluated by changing the edema volume. All 14-membered and 15-membered macrolide antibiotics significantly suppressed the development of edema. Conversely, none of the 16-membered macrolide antibiotics inhibited the growth of edema. In conclusion, compared to 16-membered macrolide antibiotics, 14-membered and 15-membered macrolide antibiotics have stronger anti-inflammatory effects. Further research should be done to determine why different lactone ring sizes should have distinct anti-inflammatory effects.

Anti-edematous effects of epinastine, cetirizine and its enantiomers in λ-carrageenan-induced edema in rat hind paw.

Urticaria is induced by the histamine released from mast cells which develops wheals (edema) as a visual feature. In clinical practice, second-generation histamine H1 -receptor blockers are routinely used as the first-line symptomatic treatment for urticaria. Nevertheless, not much research has directly examined the second-generation histamine H1-receptor blockers' ability to reduce edema. In this study, we directly evaluated the anti-edematous activities of three second-generation histamine H1-receptor blockers available in the market (epinastine hydrochloride, cetirizine hydrochloride, and levocetirizine hydrochloride) using a λ-carrageenan-induced footpad edema model. One hour before the induction of edema with 1% λ -carrageenan injection, all second-generation histamine H1 -receptor blockers (5, 10, 50 and 100 mg/kg) were subcutaneously administered to rats. At 0.5 and 3 hours after λ -carrageenan administration, the edema volume was evaluated using a Plethysmometer. Epinastine hydrochloride significantly suppressed the edema growth in a dose-dependent manner. Cetirizine hydrochloride showed a slight anti-edematous effect, while levocetirizine significantly inhibited the development of edema in a dose-dependent manner. On the other hand, dextrocetirizine did not prevent edema from growing. In summary, second-generation histamine H1 -receptor blockers, at least those examined in this study, may be able to reduce the clinical symptoms of urticaria associated with edema. Levocetirizine hydrochloride is also anticipated to have stronger anti-edematous effects than cetirizine hydrochloride because levocetirizine is responsible for cetirizine's anti-edematous activity.

Masticatory Behavior Change with a Wearable Chewing Counter: A Randomized Controlled Trial.

Because a relationship has been reported between masticatory behavior, obesity, and postprandial blood glucose, it is recommended to chew well and take a longer time to eat. The purpose of this study was to examine the possibility of changing masticatory behavior using a small ear-hung wearable chewing counter, which can monitor masticatory behavior without disturbing daily meals. In total, 235 healthy volunteers participated in a 4-wk randomized controlled trial and were divided into 3 groups. All participants were instructed about the importance of mastication at the first visit. During the intervention, group B used the chewing counter without an algorithm during each meal (notification of the number of chews after meal), and group C used the chewing counter with a masticatory behavior change algorithm (setting a target value and displaying the number of chews in real time). Group A was set as the control group. The number of chews and the meal time when consuming 1 rice ball (100 g) were measured before and after the intervention using the chewing counter, and the rate of change in these values was evaluated. Participants also provided a subjective evaluation of their changes in masticatory behavior. The number of chews and the meal time of 1 rice ball increased significantly in groups B and C compared with before the intervention, and the rate of change was significantly higher in group C than in group A and group B. In addition, the subjective evaluation of the change in the number of chews was highest in group C. Self-monitoring of masticatory behavior by providing a target value and the degree of achievement for the number of chews using a wearable chewing counter with a behavioral change algorithm could promote effective change in masticatory behavior and lead to an increased number of chews. (Trial ID: UMIN000034476).

Epstein-Barr virus-associated inflammatory pseudotumor variant of follicular dendritic cell sarcoma of the liver: a case report and review of the literature.

BACKGROUND: Follicular dendritic cell sarcoma is a rare stromal tumor with no standard treatment. However, some reports have revealed that follicular dendritic cell sarcoma has an inflammatory pseudotumor variant associated with Epstein-Barr virus infection that has a relatively good prognosis. In this report, we present a case of a resected inflammatory pseudotumor variant of follicular dendritic cell sarcoma of the liver, and have reviewed the literature on the clinicopathological, molecular, and genomic features of this tumor. CASE PRESENTATION: The inflammatory pseudotumor variant of follicular dendritic cell sarcoma originates only in the liver or spleen, causes no symptoms, and is more common in middle-aged Asian women. It has no characteristic imaging features, which partially explains why the inflammatory pseudotumor variant of follicular dendritic cell sarcoma is difficult to diagnose. Pathologically, the inflammatory pseudotumor variant of follicular dendritic cell sarcoma has spindle cells mixed with inflammatory cells and is variably positive for follicular dendritic cell markers (CD21, CD23, and CD35) and Epstein-Barr virus-encoded RNA. On genetic analysis, patients with this tumor high levels of latent membrane protein 1 gene expression and extremely low levels of host C-X-C Chemokine Receptor type 7 gene expression, indicating that the inflammatory pseudotumor variant of follicular dendritic cell sarcoma has a latent Epstein-Barr virus type 2 infection. CONCLUSIONS: The inflammatory pseudotumor variant of follicular dendritic cell sarcoma is an Epstein-Barr virus-associated tumor and a favorable prognosis by surgical resection, similar to Epstein-Barr virus-associated gastric cancer.

Gastrectomy with or without omentectomy for cT3-4 gastric cancer: a multicentre cohort study.

BACKGROUND: Omentectomy is performed widely for locally advanced gastric cancer to prevent disease recurrence. However, its clinical benefit is unknown. METHODS: This retrospective cohort study compared the outcome of gastrectomy with preservation of the omentum (GPO) and gastrectomy with resection of the omentum (GRO) among patients with cT3-T4 gastric cancer who underwent gastrectomy between 2006 and 2012 in one of five participating institutions. A consensus conference identified 28 variables potentially associated with outcome after gastrectomy for the estimation of propensity scores, and propensity score matching (PSM) was undertaken to control for possible confounders. Postoperative surgical outcomes, overall survival and disease recurrence were compared between GPO and GRO. RESULTS: A total of 1758 patients were identified, of whom 526 remained after PSM, 263 in each group. Median follow-up was 4·9 (i.q.r. 3·1-5·9) years in the GRO group and 5·0 (2·5-6·8) years in the GPO group. The incidence of postoperative complications of Clavien-Dindo grade III or more was significantly higher in the GRO group (17·5 versus 10·3 per cent; P = 0·016). Five-year overall survival rates were 77·1 per cent in the GRO group and 79·4 per cent in the GPO group (P = 0·749). There were no significant differences in recurrence rate or pattern of recurrence between the groups. CONCLUSION: Overall survival and disease recurrence were comparable in patients with cT3-4 gastric cancer who underwent GPO or GRO.

ANTECEDENTES: La omentectomía se realiza ampliamente en el cáncer gástrico localmente avanzado para prevenir la recidiva de la enfermedad. Sin embargo, se desconoce su beneficio clínico. MÉTODOS: Este estudio retrospectivo comparó el resultado de la gastrectomía con preservación del omento (gastrectomy with preservation of the omentum, GPO) con la gastrectomía con resección del omento (gastrectomy with resection of the omentum, GRO) para el cáncer gástrico con estadio clínico T3/T4. Se incluyeron pacientes sometidos a gastrectomía por cáncer gástrico clínico T3/T4 (2006-2012) y se recogieron datos relevantes de 5 hospitales participantes. A través de una conferencia de consenso se identificaron 28 variables potencialmente asociadas con el resultado tras la gastrectomía, mediante las cuales se estimaron las puntuaciones de propensión, utilizándose el emparejamiento por puntuación de propensión (propensity score matching, PSM) para el control de posibles factores de confusión. Los resultados quirúrgicos postoperatorios, la supervivencia global y la recidiva de la enfermedad se compararon entre las gastrectomías con GPO y GRO. RESULTADOS: En total, se identificaron 1.758 pacientes, seleccionándose 526 (263 GRO y 263 GPO) tras el PSM. La mediana (rango intercuartílico) de seguimiento fue de 4,9 años (3,1-5,9) en el grupo GRO y de 5,0 años (2,5-6,8) en el grupo GPO. La incidencia de complicaciones postoperatorias de Clavien-Dindo grado III o más alto fue significativamente más elevada en el grupo GRO que en el grupo GPO (17,1% versus 9,1%; P = 0,010). La supervivencia global a los 5 años fue del 77,1% para el grupo GRO y del 79,4% para el grupo GPO (P = 0,749). No hubo diferencias estadísticamente significativas en la tasa de recidiva o patrón de recidiva entre ambos grupos. CONCLUSIÓN: La supervivencia global y la recidiva de la enfermedad son comparables en pacientes con cáncer gástrico estadio clínico T3-4 sometidos a GPO o GRO.

Scrubbing technique for needleless connectors to minimize contamination risk.

This study aimed to investigate the appropriate scrubbing technique for needleless connectors to minimize contamination risk. To demonstrate a highly effective scrubbing technique to physically eliminate bacteria, needleless connectors were contaminated with Geobacillus stearothermophilus spores and then scrubbed. The study showed that the highest bacterial elimination rate was achieved by scrubbing an access port in a straight line with an alcohol cotton swab, applying a force that was almost equal to an arterial compression haemostasis to the access port, and repeating this procedure once using a new alcohol cotton swab.

A comparison of operative and margin outcomes from surgeon learning curves in robot assisted radical prostatectomy in a changing referral practice.

Introduction The aim of this study was to explore the impact of increasing proportions of high risk referrals on surgical margin outcomes of a surgeon's learning curve in robotic prostatectomy. Methods All patients in this study underwent robot assisted radical prostatectomy (RARP) performed by three different consultant urological surgeons. Data collected included preoperative clinical stage, Gleason score and prostate specific antigen levels, which were used to risk stratify patients according to National Institute for Health and Care Excellence criteria. Oncological clearance was assessed by overall and stage specific positive margin status. Comparisons were made between each surgeon for the first and second 50 consecutive cases. Results For the three surgeons, there was a progressive increase in the proportion of high risk cases referred accompanied by a corresponding decline in low risk disease (p<0.001). Postoperative pathology also showed an upward trend in pT3 cases across the three eras. There was no statistical difference in overall positive margin rates between the surgeons. The overall rates were 12%, 20% and 23% for the first 50 cases, and 32%, 36% and 21% for the second 50 cases for the three surgeons respectively. Conclusions Our series demonstrates an upward trend in the risk profile of men referred for robotic prostatectomy over a nine-year period. Despite this, there was minimal impact on pathological and surgical outcomes among our surgeons, who were at the initial stages of their RARP learning curve. Our results suggest that there is no requirement for an active case selection bias against patients with high risk disease for surgeons newly embarking on their RARP learning experience.

Renal pseudoaneurysm: a rare and potentially fatal complication following ureteroscopy and laser fragmentation of stones.

Ureteroscopy and laser fragmentation of stones is a commonly used method to treat ureteric and renal calculi. We report the exceedingly rare finding of a renal pseudoaneurysm in an interpolar renal artery following ureteroscopy and laser stone fragmentation, which was successfully managed with angioembolisation.

Evaluation of economic burden of colonic surgical site infection at a Japanese hospital.

BACKGROUND: Several reports have been published regarding cost increases attributable to surgical site infections (SSIs) in Europe and the USA. However, such studies have been limited in Japan. AIM: To evaluate the economic burden of colorectal SSIs on hospitals in Japan. METHODS: This study was undertaken at a Japanese university hospital. Amongst 265 patients who had undergone colorectal surgery in the Department of Coloproctological Surgery between November 2014 and March 2016, 16 patients who developed SSIs and could be allocated a diagnosis procedure combination code were selected as SSI cases. Individual SSI cases were matched to non-SSI cases based on a combination of surgical category, age band, sex, wound class, presence of stoma and risk index. Median length of stay (LOS) and piecework reference cost were compared between SSI episodes and non-SSI episodes. FINDINGS: The median LOS for patients with SSI and without SSI was 25.5 [interquartile range (IQR) 21.5-39.3] and 16.5 (IQR 12.5-18.5) days, respectively (P<0.01). The median piecework reference cost for patients with SSI and without SSI was ¥842,155 (IQR ¥716,423-1,388,968) and ¥575,795 (IQR ¥529,638-680,105), respectively (P<0.01). CONCLUSION: SSIs led to a significant increase in LOS and economic burden. Although the SSI episodes appear to be more profitable than the non-SSI episodes, the economic profit for SSI episodes was less than that for non-SSI episodes in the observation period, when opportunity costs were taken into account.

Prediction of hemorrhagic transformation after acute thrombolysis following major artery occlusion using relative ADC ratio: A retrospective study.

BACKGROUND: The relative apparent diffusion coefficient (ADC) ratio can be used to evaluate the extent of ischemia. We investigated the risk factors for, and correlation between, relative ADC ratio and hemorrhagic transformation (HT) after thrombolysis. METHODS: This single-center, retrospective study involved 105 patients with acute occlusion of the anterior circulation. Relative ADC ratio was calculated as the ratio of ADC pixel values, within the affected territory to ADC pixel values in the contralateral normal region. HT was determined by computed tomography and T2* weighted magnetic resonance imaging after endovascular revascularization. RESULTS: Data for 80 of the 105 patients were analyzed. Comparing the number of patients between the HT group (n=25) and the non-HT group (n=55), a significant difference was noted in tissue plasminogen activator (tPA) use (P=0.028), time from onset to reperfusion ≥380min (P<0.001), fluid-attenuated inversion recovery (FLAIR) hyperintensity (P=0.009), and relative ADC ratio<0.650 (P<0.001). Multivariable logistic regression analysis identified relative ADC ratio<0.650 as the only independent predictor of HT (odds ratio 7.79; 95% confidence interval 2.22-27.3; P=0.001). Twenty-nine patients (including 20 in the HT group) had a relative ADC ratio<0.650. Multivariable logistic regression analysis identified use of tPA as the only independent predictor of HT (odds ratio 13.8; 95% confidence interval 1.35-125.5; P=0.010). CONCLUSIONS: Relative ADC ratio<0.650 with use of tPA may be important for predicting HT.

Effect of Gender Differences on Transplant Kidney Function.

BACKGROUND: Transplant kidney function is thought to be affected by sex differences, such as physical conditions including muscle volume, sex hormones, immune responses, and so forth. We examined the effect of sex differences on transplant kidney function. METHODS: The subjects were selected from kidney transplant recipients, who received kidney transplantation on our hospital between January 2000 and August 2015. Cadaveric donors and parent-child pairs with an age difference were excluded, then we included 47 recipients whose sex was different from the sex of the donor. We compared transplant kidney function between male donors and female recipients group (M→F, n = 20) and female donors and male recipients group (F→M, n = 27). RESULTS: Nadir creatinine value was higher in the F→M group than in the M→F group (1.09 mg/dL vs 0.76 mg/dL, P < .0001). The estimated glomerular filtration rate (eGFR) was significantly higher in the M→F group than in the F→M group (66.6 mL/min/1.73 m2 vs 50.1 mL/min/1.73 m2, P = .002), and eGFR ratio (recipient to donor) was significantly higher in the M→F group than in the F→M group (1.13 vs 0.57, P < .0001). Multiple linear regression analysis showed that the only the sex of the recipient was significant prognostic factor of eGFR after renal transplantation (P = .037). CONCLUSIONS: The short-term kidney function of the graft from male to female was better than that of the graft from female to male.

Efficacy of stabilisation splint therapy combined with non-splint multimodal therapy for treating RDC/TMD axis I patients: a randomised controlled trial.

Stabilisation splint therapy has long been thought to be effective for the management of temporomandibular disorders (TMD). However, the superiority of stabilisation splint therapy compared to other TMD treatments remains controversial. The aim of this study was to determine the efficacy of stabilisation splint therapy combined with non-splint multimodal therapy for TMD. A total of 181 TMD participants were randomly allocated to a non-splint multimodal therapy (NS) group (n = 85) or a non-splint multimodal therapy plus stabilisation splint (NS+S) group (n = 96). Non-splint multimodal therapy included self-exercise of the jaw, cognitive-behavioural therapy, self-management education and additional jaw manipulation. Three outcome measurements were used to assess treatment efficacy: mouth-opening limitation, oro-facial pain and temporomandibular joint sounds. A two-factor repeated-measures analysis of variance (anova) was used to evaluate the efficacy of the two treatment modalities (NS vs. NS+S), and Scheffe's multiple comparison test was used to compare the treatment periods. Subgroup analyses were performed to disclose the splint effects for each TMD diagnostic group. All three parameters significantly decreased over time in both groups. However, there were no significant differences between the two treatment groups in the total comparison or subgroup analyses; an exception was the group with degenerative joint disease. No significant difference between the NS and NS+S treatment approaches was revealed in this study. Therefore, we conclude that the additional effects of stabilisation splint are not supported for patients with TMD during the application of multimodal therapy.

Clinical usefulness of concentrated ascites reinfusion therapy (CART) for gynecological cancer patients with refractory massive ascites due to cancerous peritonitis.

PURPOSE: Cell-free and concentrated ascites reinfusion therapy (CART) is intended to treat patients by ultrafiltration and reinfusion of their refractory ascites. In the CART system, bacteria and cancer cells in removed massive ascites are filtrated. Then, water is removed in the condenser, resulting in a higher protein concentration. The purpose of this study was to assess the clinical usefulness of CART in the treatment of refractory massive ascites in patients with cancerous peritonitis. MATERIALS AND METHODS: CART was performed 13 times in four patients with ovarian and endometrial cancer. RESULTS: Autologous protein with a higher concentration was intravenously administered. The amount of aspirated and condensed ascites was 3,190 +/- 1,086 ml (975 4,500 ml) and 538 +/- 249 ml (100 - 860 ml), respectively. Condensed albumin, albumin concentration, and concentration time were 43.2 +/- 25.8 g, 8.2 +/- 3.3 g/dl, and 73.3 +/- 24.8 min (28 - 122 min), respectively. CART was effective in maintaining serum albumin concentrations, and it is possible to repeat infusion. During CART, patients performance status was 1-2 and vital signs were stable except for mild elevations in body temperature. Daily life was maintained without serious side-effects. CONCLUSIONS: The use of CART for gynecological cancer patients with refractory massive ascites due to cancerous peritonitis contributes to improvements in quality of life and relief of symptoms. With autologous infusion of condensed ascites, patients can avoid infection, allergic reactions, and administration of expensive blood products.

Current role of hybrid CT/angiography system compared with C-arm cone beam CT for interventional oncology.

Hybrid CT/angiography (angiography) system and C-arm cone beam CT provide cross-sectional imaging as an adjunct to angiography. Current interventional oncological procedures can be conducted precisely using these two technologies. In this article, several cases using a hybrid CT/angiography system are shown first, and then the advantages and disadvantages of the hybrid CT/angiography and C-arm cone beam CT are discussed with literature reviews.

Time course of axial and radial diffusion kurtosis of white matter infarctions: period of pseudonormalization.

BACKGROUND AND PURPOSE: Diffusion kurtosis is a statistical measure for quantifying the deviation of the water diffusion profile from a Gaussian distribution. The current study evaluated the time course of diffusion kurtosis in patients with cerebral infarctions, including perforator, white matter, cortical, and watershed infarctions. MATERIALS AND METHODS: Subjects were 31 patients, representing 52 observations of lesions. The duration between the onset and imaging ranged from 3 hours to 122 days. Lesions were categorized into 4 groups listed above. Diffusion kurtosis images were acquired with b-values of 0, 1000, and 2000 s/mm(2) applied in 30 directions; variables including DWI signal, ADC, fractional anisotropy, radial diffusivity, axial diffusivity, radial kurtosis, and axial kurtosis, were obtained. The time courses of the relative values (lesion versus contralateral) for these variables were evaluated, and the pseudonormalization period was calculated. RESULTS: Diffusion kurtosis was highest immediately after the onset of infarction. Trend curves showed that kurtosis decreased with time after onset. Pseudonormalization for radial/axial kurtosis occurred at 13.2/59.9 days for perforator infarctions, 33.1/40.6 days for white matter infarctions, 34.8/35.9 days for cortical infarctions, and 34.1/28.2 days after watershed infarctions. For perforator infarctions, pseudonormalization occurred in the following order: radial kurtosis, ADC, axial kurtosis, and DWI. CONCLUSIONS: Diffusion kurtosis variables in lesions increased early after infarction and decreased with time. Information provided by diffusion kurtosis imaging, including axial and radial kurtosis, seems helpful in conducting a detailed evaluation of the age of infarction, in combination with T2WI, DWI, and ADC.

Investigation of nasal meticillin-resistant Staphylococcus aureus carriage in a haemodialysis clinic in Japan.

Patients and healthcare workers in a Japanese haemodialysis clinic were investigated for nasal carriage of meticillin-resistant Staphylococcus aureus (MRSA). MRSA carriage was found in 10 (8.9%) of 112 patients in the first year and four (3.9%) of 103 patients in the second year. All isolated MRSA samples carried staphylococcal cassette chromosome mec type II or III and classified as clonal complex 5, which were common as healthcare-associated strains. Pulsed-field gel electrophoresis indicated horizontal transmission limited to two pairs of patients in one session. One of 54 healthcare workers carried MRSA genetically unrelated to patients' strains. Infection control measures based on the US Centers for Disease Control and Prevention's recommendation showed limited spread of MRSA in a haemodialysis room.

Triglyceride-rich lipoproteins in chronic kidney disease patients undergoing maintenance haemodialysis treatment.

OBJECTIVE: Plasma triglyceride (TG) levels were reported to be high in chronic kidney disease (CKD) patients undergoing haemodialysis (HD) treatment. One of the atherogenic causes of hypertriglyceridemia is the increase in TG-rich lipoprotein remnants, which are equivalent to remnant-like particle cholesterol (RLP-C). Here, we compared the plasma levels of TG, a representative indicator of TG-rich lipoproteins and RLP-C, as well as the TG/RLP-C ratio between CKD patients undergoing HD and controls, in an effort to elucidate the atherogenicity of TG-rich lipoproteins in CKD patients on HD. MATERIALS AND METHODS: Plasma lipid and apo(lipo)protein levels and the TG/RLP-C ratio were compared between 49 CKD patients undergoing HD and 627 controls. Blood sampling for lipid and apoprotein analysis was performed in a 12-h fasting state. Controls were divided into four subgroups according to TG level (from highest to lowest). RLP-C and apo(lipo)proteins were measured using the immunoprecipitation method and turbidimetric immunoassay, respectively. In addition, a comparison between HD patients and age-, gender-, and plasma TG level-matched controls was performed. RESULTS: Plasma TG levels were 107 ± 70 (mean ± SD) mg/dl in HD patients and 115 ± 72 mg/dl in controls. Plasma RLP-C levels were 6.7 ± 4.5 mg/dl in HD patients and 4.6 ± 3.5 mg/dl in the controls (p < 0.0001). RLP-C levels decreased in descending order from the highest to the lowest TG group in controls. RLP-C levels were higher in HD patients than in controls with plasma TG levels of < 150 mg/dl (p < 0.0001). TG/RLP-C ratios were 19.0 ± 12.0 in HD patients and 25.9 ± 9.5 in controls (p < 0.0001). This ratio was significantly lower in HD patients than in all four TG subgroups. The comparison between HD patients and age-, gender-, plasma TG-matched controls revealed identical results. CONCLUSION: Plasma RLP-C levels were high, and the TG/RLP-C ratio was low in CKD patients undergoing HD treatment. These findings indicate that total plasma TG-rich lipoprotein levels were not increased, but the distribution of plasma TG-rich lipoproteins were skewed towards remnant fractions in CKD patients undergoing HD treatment; these plasma TG-rich lipoproteins appear to be more atherogenic than those in controls.

Prediction of time-dependent interaction of aspirin with ibuprofen using a pharmacokinetic/pharmacodynamic model.

WHAT IS KNOWN AND OBJECTIVE: Low-dose aspirin is widely used for prevention of thrombosis, but combined use of aspirin with non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, reduces the antiplatelet effect of aspirin. However, there has been no report describing the effects of the timing of the ibuprofen dose on the degree of interaction between low-dose aspirin and ibuprofen. The purpose of this study was to predict the time-course of the antiplatelet effect of low-dose aspirin when ibuprofen is administered as a single dose or repeatedly in combination with aspirin at various time intervals. METHODS: We simulated ex vivo platelet aggregation using a previously developed pharmacokinetic (PK)/pharmacodynamic (PD) model. RESULTS AND DISCUSSION: The antiplatelet effect of low-dose aspirin (81 mg) was predicted to be markedly reduced when ibuprofen (200 mg; the usual prescribed dose in Japan) was administered 1 h or less after aspirin, but not when it was administered more than 2 h after the administration of aspirin. Moreover, the administration of ibuprofen up to 12 h before aspirin completely abrogated the antiplatelet effect of aspirin. When ibuprofen (200 mg) was administered three times daily for 3 days (day 1 to day 3) on a background of continuous low-dose aspirin (81 mg) once daily, 2 h after aspirin, no reduction in the antiplatelet effect of aspirin was predicted on day 1, but a reduction is predicted from day 2, with no return to the initial level until more than 3 days after discontinuation of ibuprofen. A marked reduction in the antiplatelet effect of aspirin was also seen on the same schedule when the dosage of ibuprofen was 150 mg, which is the dose used in over-the-counter (OTC) preparations. WHAT IS NEW AND CONCLUSION: This study indicates that the antiplatelet effect of low-dose aspirin can be markedly reduced with combined use of ibuprofen, depending on the timing of co-administration. As even the lower OTC dose of ibuprofen (150 mg) was enough to affect the antiplatelet effect of aspirin, health professionals should take into account patients' use of OTC ibuprofen when prescribing low-dose aspirin.