Effect of acid suppressant medications on the laxative action of magnesium preparations in patients with opioid-induced constipation: A pharmacovigilance analysis of the FDA Adverse Event Reporting System.

Objective: Magnesium oxide is widely used for treating opioid-induced constipation, a serious analgesic-associated problem. Opioid analgesic users are often prescribed non-steroidal anti-inflammatory drugs, which are sometimes combined with acid suppressants to prevent gastrointestinal adverse events. Magnesium preparations combined with acid suppressants may diminish magnesium preparations' laxative effect. This study was aimed at evaluating the effect of magnesium preparations combined with acid suppressants on the incidence of opioid-induced constipation by using the Food and Drug Administration Adverse Event Reporting System. Methods: Adverse events were defined per the Medical Dictionary for Regulatory Activities; the term 'constipation (preferred term code: 10010774)' was used for analysis. After adjusting for patient background factors using propensity score matching, acid suppressants' effect on constipation incidence was evaluated in opioid users prescribed magnesium preparations alone as laxatives by using a test for independence. Key Findings: The Food and Drug Administration Adverse Event Reporting System contains 14,475,614 reports for January 2004 to December 2021. Significantly increased constipation incidence was related to magnesium preparations combined with acid suppressants, especially proton pump inhibitors (P < 0.0001, McNemar's test). Conclusion: Magnesium preparations combined with acid suppressants may diminish magnesium preparations' laxative effect; healthcare professionals should pay attention to this issue.

Effects of royal jelly on bone metabolism in postmenopausal women: a randomized, controlled study.

OBJECTIVES: This study aimed to evaluate the effects of royal jelly (RJ) supplementation on bone metabolism in postmenopausal women. METHODS: This was a randomized, double-blind, placebo-controlled clinical trial. Seventy-two healthy postmenopausal women aged 45-60 years within 5 years after menopause were randomized into two groups: women in the RJ group (n = 36) received capsules containing dried RJ (equivalent to 3000 mg of fresh RJ); and women in the placebo group (n = 36) received placebo daily for 6 months. Bone mineral density (BMD) of the lumbar spine (L2-L4) and left proximal femur, hip structural analysis (HSA) of the left hip, and bone turnover markers were measured. RESULTS: Although women in the placebo group experienced a significant loss of BMD and deterioration in HSA parameters of the femur, no significant differences were found in these parameters in women in the RJ group. The levels of total procollagen type 1 N-terminal propeptide (P1NP) and tartrate-resistant acid phosphatase decreased significantly in the placebo group; however, the total P1NP level, a marker of bone formation, was not significantly different in the RJ group at postintervention compared with baseline. CONCLUSION: RJ consumption may ameliorate decreases in femoral BMD and strength in postmenopausal women.

Effect of therapeutic plasma exchange on phenytoin plasma concentration in patients receiving intravenous fosphenytoin therapy.

We report for patients with encephalitis treated with plasma exchange (PE) and fosphenytoin. In patient 1, phenytoin levels decreased on the maintenance dose, and the phenytoin concentration was <10 µg/mL on day 12 of administration. In patient 2, the phenytoin levels was <10 µg/mL on day 4. Increasing the fosphenytoin dose pushed the phenytoin level into therapeutic range. There were no differences between the areas under the concentration-time curve of phenytoin with and without PE. We previously reported a decline in phenytoin levels after prolonged use of fosphenytoin. Therefore, dose adjustment of fosphenytoin in patients undergoing PE may be unnecessary.

Morphological features of the posterior oblique ligament of the ulnar collateral ligament of the elbow joint.

PURPOSE: The purpose of this basic research study was to clarify the morphological characteristics of the posterior oblique fibers (POL) of the ulnar collateral ligament using a large number of specimens. METHODS: This study examined 50 arms from 25 Japanese cadavers. Type classification was performed by focusing on the positional relationship between POL morphology and the joint capsule. The morphological features measured were fiber bundle length, width, and thickness. RESULTS: The POL was classified as follows: Type I, the POL's anterior and posterior edges are located on the surface of the joint capsule and can be separated as a single fiber bundle; Type II-a, the POL anterior edge can be separated, but the posterior edge cannot be separated; Type II-b, the POL posterior edge can be separated, but the anterior edge cannot be separated; and Type III, the POL cannot be separated from the joint capsule. Type I was seen in 23 elbows (46%), Type II-a in 6 elbows (12%), Type II-b in 7 elbows (14%), and Type III in 14 elbows (28%). CONCLUSION: The results of this study suggested that the POL could be classified into an independent type and an unclear type, and the presence of the unclear type was one of the factors that caused morphological variation.

Characteristics of IgG subclasses and complement deposition in BP230-type bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune blistering disease. BP180 is the primary autoantigen of BP, and in a portion of BP cases, BP230 is the only target of autoantibodies. Such BP is called BP230-type BP. BP230-type BP tends to show milder clinical phenotypes than conventional BP, but the reason is unclear. The pathogenic roles of autoantibodies and complement activation have been shown in conventional BP, but the distribution of IgG subclasses and the degree of complement deposition in BP230-type BP remain unclear. OBJECTIVE: To compare the distribution of IgG subclasses and the degree of complement deposition in BP230-type BP with those in conventional BP with autoantibodies to BP180 and BP230 (BP180-BP230-type BP). METHODS: The diagnosis of BP was confirmed by the histopathology of the lesions, the deposition of IgG and complement in the perilesional skin and the presence of circulating autoantibodies to BP180 and BP230. The disease severity was determined by bullous pemphigoid disease area index. The deposition of IgG subclasses and complement deposition were examined by direct immunofluorescence of the perilesional skin in 6 BP230-type BP cases and 11 BP180-BP230-type BP cases. RESULTS: Sixty seven percent of BP230-type BP cases show a mild clinical phenotype. All BP230-type BP cases and 82% of BP180-BP230-type BP cases were found to demonstrate the clear deposition of IgG4 at the basement membrane zone of skin specimens. Notably, the deposition of IgG1 and IgG3 was faint or negative in all of the BP230-type BP cases, whereas they were clearly detected in 91% and 64% of the BP180-BP230-type BP cases, respectively. The deposition of complement C3 tended to be weaker in BP230-type BP than in BP180-BP230-type BP. CONCLUSION: The mild clinical phenotype of BP230-type BP may correlate with the weaker deposition of IgG1, IgG3 and complement in the skin lesions.

Fluoride-fiber-based side-pump coupler for high-power fiber lasers at 2.8 µm.

A side-pump coupler made of fluoride fibers was fabricated and tested. The tested device had a coupling efficiency of 83% and was driven with an incident pump power of up to 83.5 W, demonstrating high-power operation. Stable laser output of 15 W at a wavelength of around 2.8 µm was achieved over 1 h when using an erbium-doped double-clad fiber as the active medium. To the best of our knowledge, this is the first time a fluoride-glass-fiber-based side-pump coupler has been developed. A test with two devices demonstrated further power scalability.

Enhanced dissolution of ibuprofen using ionic liquids as catanionic hydrotropes.

The therapeutic effectiveness of a drug largely depends on its bioavailability, and thus ultimately on its aqueous solubility. Hydrotropes are compounds able to enhance the solubility of hydrophobic substances in aqueous media and therefore are extensively used in the formulation of drugs and personal care products. Recently, some ionic liquids were shown to display a strong ability to enhance the solubility of biomolecules through hydrotropy. In this work, the impact of the ionic liquid chemical structures and their concentration on the solubility of ibuprofen was evaluated and compared with the performance of conventional hydrotropes. The results obtained clearly evidence the exceptional capacity of ionic liquids to enhance the solubility of ibuprofen. [C4C1im][SCN] and [C4C1im][N(CN)2] seem to be the most promising ionic liquids for ibuprofen solubilisation, where an increase in the solubility of 60- and 120-fold was observed with ionic liquid concentrations of circa 1 mol kg-1, respectively. Dynamic light scattering and molecular dynamics simulations were used to investigate the mechanism of the IL-mediated drug solubility and the results obtained indicate that the structure of aqueous solutions of ionic liquids and the role it plays in the formation of ionic liquid-drug aggregates is the mechanism driving the hydrotropic dissolution.

Royal jelly does not prevent bone loss but improves bone strength in ovariectomized rats.

OBJECTIVE: Royal jelly (RJ) has been used for medical and nutritional purposes, and previous studies have indicated that it may have estrogenic activity. The present study investigated the effects of RJ on bone metabolism in ovariectomized (OVX) rats. METHODS: Rats (12 weeks old) were randomly divided into four groups, namely Baseline, Sham, OVX, and OVX + RJ groups. Rats in the Baseline group were killed immediately, whereas rats in the OVX and OVX + RJ groups underwent bilateral ovariectomy and those in the Sham group underwent sham operation. RJ was administered to rats in the OVX + RJ group daily for 12 weeks. At the end of the 12-week period, bone mass, bone histomorphometry, and bone mechanics were analyzed. RESULTS: Femur bone mineral density (BMD) was significantly lower in the OVX group than in the Sham group, and this decrease in BMD was not ameliorated by RJ administration. However, femur stiffness, as evaluated by a three-point bending test, was significantly higher in the OVX + RJ group than in the OVX group. CONCLUSION: The findings of the present study suggest that RJ does not prevent bone loss, but does improve bone strength in OVX rats.

Antioxidant treatment ameliorates diabetes-induced dysfunction of the vas deferens in a rat model.

Diabetes mellitus (DM) affects the male ejaculatory function. This study was designed to evaluate the role of oxidative stress in the development of diabetes-induced dysfunction of vas deferens (VD) in the rat. DM was induced by streptozotocin in 40 male Wistar rats. Subsequently, the diabetic animals were divided into three groups: DM group, DM + Eda group and DM + Tau group. These groups were administered saline, edaravone and taurine, respectively, daily for 4 weeks. Another group of ten rats served as a control group. DM was diagnosed in the 40 streptozotocin-injected rats. DM significantly reduced the VD weight. Additionally, DM induced in vitro VD hypercontractility, VD histological abnormalities and increased the serum and VD tissue concentration of malondialdehyde. VD immunohistochemistry revealed overexpression of three markers of oxidative stress. DM significantly reduced serum testosterone levels. No live birth was documented in all DM rats in mating experiments. Antioxidants significantly improved all the aforementioned parameters, except the testosterone levels. This study indicates a deleterious impact of DM-induced oxidative stress on VD histological and functional features. Antioxidant treatment may provide an adjunct tool to alleviate ejaculatory disorders for male patients with type 1 diabetes.

Intraoperative oliguria predicts acute kidney injury after major abdominal surgery.

Background: The threshold of intraoperative urine output below which the risk of acute kidney injury (AKI) increases is unclear. The aim of this retrospective cohort study was to investigate the relationship between intraoperative urine output during major abdominal surgery and the development of postoperative AKI and to identify an optimal threshold for predicting the differential risk of AKI. Methods: Perioperative data were collected retrospectively on 3560 patients undergoing major abdominal surgery (liver, colorectal, gastric, pancreatic, or oesophageal resection) at Kyoto University Hospital. We evaluated the relationship between intraoperative urine output and the development of postoperative AKI as defined by recent guidelines. Logistic regression analysis was performed to adjust for patient and operative variables, and the minimum P -value approach was used to determine the threshold of intraoperative urine output that independently altered the risk of AKI. Results: The overall incidence of AKI in the study population was 6.3%. Using the minimum P -value approach, a threshold of 0.3 ml kg -1 h -1 was identified, below which there was an increased risk of AKI (adjusted odds ratio, 2.65; 95% confidence interval, 1.77-3.97; P <0.001). The addition of oliguria <0.3 ml kg -1 h -1 to a model with conventional risk factors significantly improved risk stratification for AKI (net reclassification improvement, 0.159; 95% confidence interval, 0.049-0.270; P =0.005). Conclusions: Among patients undergoing major abdominal surgery, intraoperative oliguria <0.3 ml kg -1 h -1 was significantly associated with increased risk of postoperative AKI.

Fc-Gamma Receptor Polymorphisms Predispose Patients to Infectious Complications After Liver Transplantation.

We investigated the impact of polymorphisms in host innate immunoregulatory genes on the development of infectious complications after liver transplantation (LT). The single-nucleotide polymorphisms (SNPs) of C1QA [276A/G], FCGR2A [131H/R], and FCGR3A [158F/V], genes encoding the Fc gamma receptor (FcγR), were analyzed in 89 living donor LT recipients in relation to the occurrences of postoperative infectious complications within 30 days after LT. Consistent with a lower affinity of the isoform encoded by FCGR3A [158F] to both IgG1 and IgG3, a significantly higher incidence of bloodstream infections (BSI) was observed in the FCGR3A [158F/V or F/F] than in the FCGR3A [158V/V] individuals. The combination of FCGR2A and FCGR3A SNPs further stratified the incidence of BSI, regardless of C1QA SNP. The predominant causative pathogen of BSI in the FCGR3A [158F/F or F/V] patients was gram-positive cocci (73.3%), of which one third was methicillin-resistant Staphylococcus aureus. No differences were observed in the incidence of fungal infections or in cytomegalovirus infections with respect to the three gene polymorphisms. Our findings indicate that FcγR SNPs are predisposing factors for BSI and can predict mortality after LT. This study provides a foundation for further prospective studies on a larger scale.

Sorafenib plus hepatic arterial infusion chemotherapy with cisplatin versus sorafenib for advanced hepatocellular carcinoma: randomized phase II trial.

BACKGROUND: Sorafenib (Sor) is acknowledged as a standard therapy for advanced hepatocellular carcinoma (HCC). This trial was conducted to evaluate the effect of addition of hepatic arterial infusion chemotherapy with cisplatin (SorCDDP) to Sor for the treatment of advanced HCC. PATIENTS AND METHODS: We conducted a multicenter open-labeled randomized phase II trial in chemo-naïve patients with advanced HCC with Child-Pugh scores of 5-7. Eligible patients were randomly assigned 2:1 to receive SorCDDP (sorafenib: 400 mg bid; cisplatin: 65 mg/m2, day 1, every 4-6 weeks) or Sor (400 mg bid). The primary end point was overall survival. RESULTS: A total of 108 patients were randomized (Sor, n = 42; SorCDDP, n = 66). The median survival in the Sor and SorCDDP arms were 8.7 and 10.6 months, respectively [stratified hazard ratio (95% confidence interval), 0.60 (0.38-0.96), P = 0.031]. The median time to progression and the response rate were, respectively, 2.8 months and 7.3% in the Sor arm and 3.1 months and 21.7% in the SorCDDP arm. The adverse events were more frequent in the SorCDDP arm than in the Sor arm, but well-tolerated. CONCLUSION: SorCDDP yielded favorable overall survival when compared with Sor in patients with advanced HCC. CLINICAL TRIAL REGISTRATION: UMIN-CTR (http://www.umin.ac.jp/ctr/index-j.htm), identification number: UMIN000005703.

Cutaneous manifestations of Helicobacter cinaedi: a review.

Helicobacter cinaedi is an emerging Gram-negative spiral bacillus that was first reported in 1984. It has been implicated as a cause of gastroenteritis and bacteraemia in immunocompromised individuals. Helicobacter cinaedi-associated bacteraemia is sometimes accompanied by skin lesions; however, the cutaneous manifestations of this pathogen are not widely known. To our knowledge, a comprehensive review with detailed analysis of skin lesions associated with H. cinaedi has not been conducted. This article summarizes the clinical appearance of H. cinaedi cellulitis and its management. In addition, we conducted a retrospective review of 73 patients with H. cinaedi bacteraemia at a single institution, to further clarify the characteristic cutaneous features. It was found that 30% (22/73) of the cases of H. cinaedi bacteraemia had sudden-onset erythema accompanied by high fever. The most common cutaneous symptom of H. cinaedi bacteraemia was found to be mild cellulitis, appearing as multiple painful infiltrated erythemas on the extremities. As H. cinaedi is not always detectable in routine blood culture techniques, evaluation of these characteristic cutaneous manifestations seems important in diagnosis. Helicobacter cinaedi infection should be added to the diagnostic list of unspecified fever with painful infiltrated erythemas.

Effect of cooking classes for housewives on salt reduction in family members: a cluster randomized controlled trial.

OBJECTIVES: Sodium reduction is very important in preventing cardiovascular diseases, especially in regions with high salt intake such as Japan. One strategy for salt reduction is to raise consumer awareness of the need to reduce daily salt intake. We investigated whether cooking classes given to housewives focussing on salt reduction would influence not only their own consumption behaviour but also that of their family members. STUDY DESIGN: Single-blinded, cluster randomized trial. METHODS: We randomly assigned housewives to participate in cooking classes focussing on salt reduction (intervention group) or lectures about a healthy lifestyle (control group). The main outcome measure was the difference in estimated daily salt intake by spot urine sampling of housewives and their family members 2 months after intervention between the groups. RESULTS: A total of 35 housewives and 33 family members were randomized. The mean daily salt intake was 10.00 (standard deviation [SD] 1.75) g/day in the control group (17 housewives and 15 family members) and 9.57 (SD 2.45) g/day in the intervention group (18 housewives and 18 family members) at baseline. Two months after the intervention, the mean salt intake was 10.30 (SD 1.78) g/day in the control group and 8.95 (SD 2.45) g/day in the intervention group. The mean difference was -1.19 g/day (95% confidence interval -2.29, -0.09; P = 0.034). A similar tendency was observed in the subgroups of housewives and family members. CONCLUSIONS: Our trial suggested that the effects of cooking classes focussing on salt reduction for housewives could be transferred to family members (UMIN-CTR: 000018870).

Spectrally-efficient all-optical OFDM by WSS and AWG.

We report on the transmission experiment of seven 12.5-GHz spaced all optical-orthogonal frequency division multiplexed (AO-OFDM) subcarriers over a 35-km fiber link, using differential quadrature phase shift keying (DQPSK) modulation and direct detection. The system does not require chromatic dispersion compensation, optical time gating at the receiver (RX) or cyclic prefix (CP), achieving the maximum spectral efficiency. We use a wavelength selective switch (WSS) at the transmitter (TX) to allow subcarrier assignment flexibility and optimal filter shaping; an arrayed waveguide grating (AWG) AO-OFDM demultiplexer is used at the RX, to reduce the system cost and complexity.

Associations between the levels of sclerostin, phosphate, and fibroblast growth factor-23 and treatment with vitamin D in hemodialysis patients with low intact PTH level.

UNLABELLED: Serum sclerostin levels could be closely associated with serum phosphate and fibroblast growth factor-23 levels in hemodialysis patients with low intact parathyroid hormone (PTH) levels. Further study is required to indicate whether these close associations are present in patients with spontaneously low PTH levels without any vitamin D treatment. INTRODUCTION: Intact parathyroid hormone (iPTH) is involved in the interaction between sclerostin and phosphate/fibroblast growth factor-23 (FGF23) in animal models. However, their relationship in patients on hemodialysis (HD) is unclear. METHODS: Data of 102 HD patients were collected regarding clinical and laboratory parameters and mineral bone disorder medications. The patients were divided into subgroups according to the iPTH level (A, <70 pg/mL; B, 70-150 pg/mL; C, 150-300 pg/mL; and D, ≥ 300 pg/mL). RESULTS: The sclerostin level was significantly and positively correlated with phosphate and log of FGF23 levels in subgroups A, B, and combined A and B. Multiple linear regression analysis in the combined A and B subgroup revealed that male sex (t = 3.24, P = 0.01; 95% confidence interval [CI] 11.78 to 50.43) and phosphate level (t = 2.13, P = 0.04; 95% CI, 1.08 to 36.91) were independent factors for serum sclerostin level. The log of serum FGF23 level (t = 1.90, P = 0.06, 95% CI -1.85 to 63.50) appeared to be an important factor for serum sclerostin level. The frequency of patients using vitamin D treatment was not significantly different among subgroups A (93.1%), B (88.0%), C (85.2%), and D (90.5%). CONCLUSION: Serum sclerostin levels were associated with serum phosphate and FGF23 levels in patients with low iPTH levels. Further study is required to indicate whether these close associations are present in patients with spontaneously low iPTH levels without vitamin D treatment.

Production of cis-11-eicosenoic acid by Mortierella fungi.

AIM: To find cis-11-eicosenoic acid (20:1ω9, EA)-producing micro-organisms. METHODS AND RESULTS: We found EA-producing fungi by screening about 300 fungal strains and identified a major fatty acid accumulated in the Mortierella fungi as EA by means of GC-MS analysis. In particular, Mortierella chlamydospora CBS 529.75 produced a high amount of EA (36.3 mg g(-1) of dried cells) on cultivation at 28°C for 4 days and then at 12°C for 3 days. In the result of lipid analysis, most of the EA was a component of triacylglycerols, not phospholipids. CONCLUSION: We found that M. chlamydospora CBS 529.75 was the best producer for the microbial production of EA. SIGNIFICANCE AND IMPACT OF THE STUDY: EA is beneficial as a raw material for medical supplies and a moisturizing component of cosmetic creams. This is the first report of microbial production of EA.

Elevated receptor for activated C kinase 1 expression is involved in intracellular Ca2+ influx and potentially associated with compromised regulatory T cell function in patients with asthma.

BACKGROUND: Regulatory T cells (T(regs)) are activated during anergy in response to T cell receptor (TCR) activation and functional immune suppression. Anergy of paediatric T(regs) is partially dependent on intracellular calcium mobility; following TCR activation, T(regs) do not exhibit increased intracellular Ca(2+) concentration ([Ca(2+) ](i)). OBJECTIVE: We determined whether [Ca(2+) ](i) in adult T(regs) defined their anergy, if intracellular Ca(2+) movement was linked to regulatory functions, whether [Ca(2+)](i) was indicative of asthma pathology, and the potential molecular mechanism responsible for Ca(2+) movement in T(regs). METHODS: T(regs) were purified by the magnetic bead method, and their regulatory functions were assessed by monitoring carboxyfluorescein succinimidyl ester-labelled responder T cell proliferation. The Ca(2+) response of Fura-2-labelled cells was measured using a video image analysis system. To analyse the functions of T(regs) at the molecular level, we generated Jurkat Tet-On(®) clones with doxycycline (Dox)-induced forkhead box P3 (FOXP3) protein expression. RESULTS: CD4(+) CD25(+) CD127(-/low) T(regs) from participants without asthma did not elicit Ca(2+) influx in response to TCR activation, exhibited little proliferation and suppressed proliferation of CD4(+) CD25(-) T cells. In contrast, under similar conditions, T(regs) from patients with asthma exhibited increased [Ca(2+)](i) and robust proliferation with partial loss of regulatory functions. FOXP3 protein levels in Tet-On(®) clones were high after both 2- and 5-day Dox treatment; however, 5-day cells were comparable with T(regs) from patients with asthma, whereas 2-day cells were similar to T(regs) from participants without asthma. Increasing [Ca(2+)](i) induced a high level of receptor for activated C kinase 1 (RACK1) expression in 5-day cells. CONCLUSIONS AND CLINICAL RELEVANCE: We confirmed that T(regs) in patients with asthma are functionally impaired and that the abnormal regulatory functions of these cells can be analysed by [Ca(2+)](i) following TCR engagement. Furthermore, the impaired functioning of T(regs) evident in patients with asthma may be due to a high level of RACK1.