Analysis of factors contributing to medication errors during self-management of medication in the rehabilitation ward: a case control study.

BACKGROUND: In the rehabilitation ward, many elderly patients require continuous use of medication after a stroke or bone fracture, even after discharge. They are encouraged to self-manage their medications from the time of admission. Medication errors, such as a missed dose or incorrect administered medication can worsen conditions, resulting in recurrent strokes, fractures, or adverse effects. The study was aimed to identify risk factors, such as medication and prescription, contributing to errors in self-management of medication. METHODS: This study was conducted on patients who self-managed their medication in the rehabilitation ward of Higashinagoya National Hospital from April 2018 to March 2020. The patient background including age and sex were investigated. The medication factors examined include the number of medications and administrations per day, dosing frequency on indicated days, prescription and start date are the same, medications from multiple prescriptions, and one package or one tablet at each dosage. The group of medication error cases were defined as the medication error group and that of control cases as the no-medication error group. A logistic regression analysis was performed for factors related to medication errors. RESULTS: A total of 348 patients were included in the study, of which 154 patients made medication errors, with 374 total medication error cases. The median number of medications in the medication error group was six, and that in the no-medication error group was five. Statistically significant factors correlated with errors made during self-management of medication were the number of medications, number of administrations per day, dosing frequency on indicated days, and medication from multiple prescriptions. CONCLUSIONS: When a patient is self-managing their medications, errors are likely to occur due to a high number of medicines they are taking and the complexity of the dosage regimen. Therefore, to prevent medication errors, reviewing the prescribed medications and devise ways to simplify the dosage regimens is crucial.

The Effectiveness of Mobile Cloud 12-Lead Electrocardiogram Transmission System in Patients with ST-Segment Elevation Myocardial Infarction.

Backgroundand Objectives: Delay of reperfusion therapy is related to high mortality in cases of ST-segment elevation myocardial infarction (STEMI). Guidelines emphasize that the first-medical-contact-to-balloon (FMCTB) time should be within 90 min. A mobile cloud-based 12-lead electrocardiogram (MC-ECG) transmission system might be useful in such cases, especially in rural areas. Materials and Methods: From April 2019 to June 2021, both an MC-ECG transmission system and the conventional method in which a physician checks the ECG in a hospital (Conventional) were used for transport by emergency medical services in Shin-Yukuhashi Hospital, Fukuoka, Japan. During this period, 8684 consecutive patients were transported to this hospital. Among them, we investigated 48 STEMI patients. The MC-ECG group (n = 23) and the Conventional group (n = 25) were enrolled. Results: There was no significant difference in FMCTB time between the MC-ECG and Conventional groups (MC-ECG: 72.0 (60.5-107) min vs. Conventional: 80.0 (63.0-92.0) min, p = 0.77). The length of hospital stay in the MC-ECG group was significantly shorter than that in the Conventional group (12.0 (10.0-15.0) days vs. 16.0 (12.0-19.0) days, p = 0.039). The logistic regression model showed that patients' non-use of MC-ECG was associated with a risk of more than 15-day length of hospital stay with an adjusted odd ratio of 0.08 (95% CI: 0.013-0.55, p = 0.0098). Conclusions: Using the MC-ECG, the length of hospital stay in patients with STEMI was significantly reduced.

Simple Synthesis of a Heterocyclophane Exhibiting Anti-c-Met Activity by Acting as a Hatch Blocking Access to the Active Site*.

A simple approach to the synthesis of heterocyclophane consisting of two 4,4'-bithiazoles has been developed in mild conditions. The heterocyclophane with two short chains was conveniently prepared by Hantzsch thiazoles synthesis using the reaction of 3-tert-butoxycarbonyl-3-azapentanethiocarboxamide with 1,4-dibromobutane-2,3-dione in methanol under reflux for only 15 min. Amino groups at the linkers of this heterocyclophane can be functionalized to give acylated and carbamate derivatives. Their properties as protein kinase inhibitors were investigated, and one of the heterocyclophanes exhibited specific anti-activity for c-mesenchymal epithelial transition factor (IC50 =603 nm), among seven types of protein kinases investigated. The computational site identification by ligand competitive saturation method was used to determine why the one heterocyclophane exhibited strong anti-activity for c-mesenchymal epithelial transition factor.

Involvement of cannabinoid type 1 receptor in fasting-induced analgesia.

The endocannabinoid system (ECS) is known to modulate not only food intake but also pain, especially via the cannabinoid type 1 receptor (CB1R) expressed throughout the central nervous system and the peripheral tissues. Our previous study demonstrated that fasting produces an analgesic effect in adult male mice, which is reversed by intraperitoneal (i.p.) administration of CB1R antagonist (SR 141716). In the present study, we further examined the effect of CB1R expressed in the peripheral tissues. In the formalin-induced inflammatory pain model, i.p. administration of peripherally restricted CB1R antagonist (AM 6545) reversed fasting-induced analgesia. However, intraplantar administration of SR 141716 did not affect fasting-induced analgesia. Furthermore, mRNA expression of CB1R did not change in the formalin model by fasting in the dorsal root ganglia. The formalin-induced c-Fos expression at the spinal cord level was not affected by fasting, and in vivo recording from the superficial dorsal horn of the lumbar spinal cord revealed that fasting did not affect formalin-induced neural activity, which indicates minimal involvement of the spinal cord in fasting-induced analgesia. Finally, when we performed subdiaphragmatic vagotomy to block the hunger signal from the gastrointestinal (GI) system, AM 6545 did not affect fasting-induced analgesia, but SR 141716 still reversed fasting-induced analgesia. Taken together, our results suggest that both peripheral and central CB1Rs contribute to fasting-induced analgesic effects and the CB1Rs in the GI system which transmit fasting signals to the brain, rather than those in the peripheral sensory neurons, may contribute to fasting-induced analgesic effects.

Responsiveness of lumbosacral superficial dorsal horn neurons during the voiding reflex and functional loss of spinal urethral-responsive neurons in streptozotocin-induced diabetic rats.

AIMS: Sensory information from the lower urinary tract (LUT) is conveyed to the spinal cord to trigger and co-ordinate micturition. However, it is not fully understood how spinal dorsal horn neurons are excited during the voiding reflex. In this study, we developed an in vivo technique allowing recording of superficial dorsal horn (SDH) neurons concurrent with intravesical pressure (IVP) during the micturition cycle in both normal and diabetic rats. METHODS: Lumbosacral dorsal horn neuronal activity and IVP were recorded from urethane-anesthetized naive and streptozotocin (STZ)-induced diabetic rats. Saline was continuously perfused into the urinary bladder through a cannula to induce micturition. RESULTS: We classified SDH neurons into bladder- and urethral-responsive neurons, based on their responsiveness during the voiding reflex. Bladder-responsive SDH neurons responded to the rapid increase in IVP at the start of voiding. In contrast, urethral-responsive SDH neuronal firing increased at the peak IVP and their firing lasted during the voiding phase (the high-frequency oscillations). Urethral-responsive SDH neurons were more sensitive to capsaicin, received C afferent fiber inputs, and were rarely detected in STZ-diabetes rats. Administration of a cyclohexenoic long-chain fatty alcohol (TAC-302), which is reported to promote neurite outgrowth of peripheral nerves in STZ-diabetic rats, prevented the functional loss of spinal urethral response. CONCLUSIONS: Sensory information from the bladder and urethra is conveyed separately to different groups of SDH neurons. Functional loss of spinal urethral sensory information through unmyelinated C afferent fibers may contribute to diabetic bladder dysfunction.

Development of a novel one-step production system for injectable liposomes under GMP.

There are few methods available for injectable liposome production under good manufacturing practices (GMP). Injectable liposome production processes under GMP generally consist of liposome formation, size homogenization, organic solvent removal, liposome concentration control and sterilization. However, these complicated and separate processes make it difficult to maintain scalability, reproducibility and sterility. To overcome these limitations, we developed a novel one-step in-line closed liposome production system that integrated all production processes by combining the in-line thermal mixing device with modified counterflow dialysis. To validate the system, we produced liposomal cyclosporine A (Lipo-CsA) and lyophilized the liposomes. The three independent pilot batches were highly reproducible and passed the quality specifications for injectable drugs, demonstrating that this system could be used under GMP. The accelerated stability test suggested that the liposomes would be stable in long-term storage. This one-step system facilitates a fully automated and unattended production of injectable liposomes under GMP.

Bcl-xL Is Essential for the Survival and Function of Differentiated Neurons in the Cortex That Control Complex Behaviors.

UNLABELLED: Apoptosis plays an essential role during brain development, yet the precise mechanism by which this pathway is regulated in the brain remains unknown. In particular, mammalian cells are known to express multiple anti-apoptotic Bcl-2 family proteins. However, the cells of the developing brain could also exist in a primed state in which the loss of a single anti-apoptotic Bcl-2 family protein is sufficient to trigger apoptosis. Here, we examined the critical role of Bcl-xL, an anti-apoptotic protein, during brain development. Using conditional knock-out mice in which Bcl-xL is deleted in neural progenitor cells (Bcl-xL(Emx1-Cre)), we show that the loss of Bcl-xL is not sufficient to trigger apoptosis in these proliferating progenitors. In contrast, specific populations of postmitotic neurons derived from these progenitors, including upper layer cortical neurons and the CA1-CA3 regions of the hippocampus, were acutely dependent on Bcl-xL. Consistent with this finding, deletion of Bcl-xL selectively in the postmitotic neurons in the brain (Bcl-xL(Nex-Cre)) also resulted in similar patterns of apoptosis. This Bcl-xL deficiency-induced neuronal death was a consequence of activation of the apoptotic pathway, because the cell death was rescued with codeletion of the proapoptotic proteins Bax and Bak. Importantly, the loss of these Bcl-xL-dependent neurons led to severe neurobehavioral abnormalities, including deficits in motor learning, hyperactivity, and increased risk-taking and self-injurious behaviors. Together, our results identify a population of neurons in the developing brain that are acutely dependent on Bcl-xL during the peak period of synaptic connectivity that are important for the establishment of higher-order complex behaviors. SIGNIFICANCE STATEMENT: Although Bcl-xL is known to inhibit apoptosis, exactly which cells in the brain are dependent on Bcl-xL has remained unclear because of the embryonic lethality of mice globally deleted for Bcl-xL. Here, we conditionally deleted Bcl-xL in the brain and found that this did not result in widespread apoptosis in the proliferating progenitors. Instead, Bcl-xL deficiency induced apoptosis in a select population of differentiated neurons predominantly in the early postnatal stages. Importantly, these Bcl-xL-dependent neurons are not essential for survival of the organism but instead regulate complex behaviors. Our results show that the selective loss of these Bcl-xL-dependent neurons results in mice exhibiting severe neurobehavioral abnormalities, including self-injurious and risk-taking behaviors, hyperactivity, and learning and memory defects.

Clinical Impact of Aprepitant in Patients Receiving High-Dose Chemotherapy prior to Autologous Peripheral Blood Stem Cell Transplantation: A Cost-Effectiveness Analysis.

OBJECTIVE: To evaluate the clinical and cost benefits of the administration of aprepitant for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV) during high-dose chemotherapy (HDCT). METHODS: We retrospectively reviewed the charts of patients who received HDCT at our institution between January 2009 and December 2013. Cost-effectiveness was analyzed using direct medical costs. RESULTS: We identified a total of 38 patients (27 with non-Hodgkin lymphoma and 11 with multiple myeloma). Thirteen patients received aprepitant and granisetron (aprepitant group) for CINV prophylaxis, whereas 25 patients received granisetron only (non-aprepitant group). The incidence of severe nausea (≥grade 3) was significantly lower in the aprepitant group than in the non-aprepitant group (p = 0.039). The total mean cost per patient during hospitalization, excluding the cost of HDCT and transplantation, was USD 10,941.8 in the aprepitant group and USD 14,577.2 in the non-aprepitant group (p = 0.041). This cost benefit reflected reductions in the costs of hospitalization, transfusion, and infection treatment. CONCLUSIONS: Our data indicated that the addition of aprepitant for CINV prophylaxis during HDCT reduced the incidence of severe nausea and might also provide economic benefit in the overall management of HDCT prior to autologous peripheral blood stem cell transplantation.

Possible benefits of tomato juice consumption: a pilot study on irradiated human lymphocytes from healthy donors.

BACKGROUND: Reactive oxygen species (ROS) mediate much of the DNA damage caused by ionizing radiation. Among carotenoids, lycopene and ß-carotene, present in tomato juice, are known to be strong radical scavengers. The aim of the study was to investigate the effect of tomato juice intake on the levels of DNA damage and oxidative stress in human whole blood induced by in vitro exposure to X-rays. METHODS: Ten healthy adults were asked to drink 190 g of tomato juice, containing 17 mg lycopene and 0.25 mg ß-carotene, per day for 3 weeks and then refrain from drinking it for 3 weeks. Peripheral whole blood samples were collected before and after the intake period of tomato juice and after the washout period. The blood samples were exposed in vitro to X-ray doses of 0, 0.1, 0.5, and 2 Gy. Cytogenetic damage was measured using the cytokinesis-block micronucleus (CBMN) assay and the dicentrics (DIC) assay. The level of oxidative stress was determined using serum 8-oxo-7, 8-dihydro-2-deoxyguanosine (8-oxo-dG) and plasma reactive oxygen metabolite-derived compounds (d-ROMs). The concentration of carotenoids in plasma was measured at the three time points. RESULTS: The levels of 8-oxo-dG tended to decrease during the intake period and increase during the washout period. A non-significant inverse correlation was noted between the plasma concentration of lycopene plus ß-carotene and the level of 8-oxo-dG (P = 0.064). The radiation-induced MN and DIC frequencies increased in a dose-dependent manner, and when compared at the same dose, the MN and DIC frequencies decreased during the intake period compared with those at baseline and then increased during the washout period. The results suggest that continuous tomato juice consumption non-significantly decreases extracellular 8-oxo-dG, d-ROMs, and MN. Tomato juice intake had minimal or no effect on radiation-induced 8-oxo-dG and d-ROMs. For most radiation doses, continuously tomato juice intake lowered the levels of MN and DIC. CONCLUSION: Tomato juice consumption may suppress human lymphocyte DNA damage caused by radiation, but further examination is required. TRIAL REGISTRATION: 2014-001 and 2014-R06.

Significance of the percentage of cholesterol efflux capacity and total cholesterol efflux capacity in patients with or without coronary artery disease.

We hypothesized that cholesterol efflux capacity is more useful than the lipid profile as a marker of the presence and the severity of coronary artery disease (CAD). Therefore, we investigated the associations between the presence and the severity of CAD and both the percentage of cholesterol efflux capacity and total cholesterol efflux capacity and the lipid profile including the high-density lipoprotein cholesterol (HDL-C) level in patients who underwent coronary computed tomography angiography (CTA). The subjects consisted of 204 patients who were clinically suspected to have CAD and underwent CTA. We isolated HDL from plasma by ultracentrifugation and measured the percentage of cholesterol efflux capacity using 3H-cholesterol-labeled J774 macrophage cells and calculated total cholesterol efflux capacity as follows: the percentage of cholesterol efflux capacity/100× HDL-C levels. While the percentage of cholesterol efflux capacity was not associated with the presence or the severity of CAD, total cholesterol efflux capacity and HDL-C in patients with CAD were significantly lower than those in patients without CAD. In addition, total cholesterol efflux capacity and HDL-C, but not the percentage of cholesterol efflux capacity, significantly decreased as the number of coronary arteries with significant stenosis increased. Total cholesterol efflux capacity was positively correlated with HDL-C, whereas the percentage of cholesterol efflux capacity showed only weak association. In a logistic regression analysis, the presence of CAD was independently associated with total cholesterol efflux capacity, in addition to age and gender. Finally, a receiver-operating characteristic curve analysis indicated that the areas under the curves for total cholesterol efflux capacity and HDL-C were similar. In conclusion, the percentage of cholesterol efflux capacity using the fixed amount of isolated HDL was not associated with CAD. On the other hand, the calculated total cholesterol efflux capacity that was dependent of HDL-C levels had a significant correlation with the presence of CAD.

The Progranulin Cleavage Products, Granulins, Exacerbate TDP-43 Toxicity and Increase TDP-43 Levels.

Mutations in the human progranulin gene resulting in protein haploinsufficiency cause frontotemporal lobar degeneration with TDP-43 inclusions. Although progress has been made in understanding the normal functions of progranulin and TDP-43, the molecular interactions between these proteins remain unclear. Progranulin is proteolytically processed into granulins, but the role of granulins in the pathogenesis of neurodegenerative disease is unknown. We used a Caenorhabditis elegans model of neuronal TDP-43 proteinopathy to specifically interrogate the contribution of granulins to the neurodegenerative process. Complete loss of the progranulin gene did not worsen TDP-43 toxicity, whereas progranulin heterozygosity did. Interestingly, expression of individual granulins alone had little effect on behavior. In contrast, when granulins were coexpressed with TDP-43, they exacerbated its toxicity in a variety of behaviors including motor coordination. These same granulins increased TDP-43 levels via a post-translational mechanism. We further found that in human neurodegenerative disease subjects, granulin fragments accumulated specifically in diseased regions of brain. To our knowledge, this is the first demonstration of a toxic role for granulin fragments in a neurodegenerative disease model. These studies suggest that presence of cleaved granulins, rather than or in addition to loss of full-length progranulin, may contribute to disease in TDP-43 proteinopathies.

Speeding up the clock: The past, present and future of progeria.

Progeria is a devastating disorder in which patients exhibit signs of premature aging. The most well-known progeroid syndromes include Hutchinson-Gilford Progeria Syndrome (HGPS) and Werner Syndrome (WS). While HGPS and WS are rare, they often result in severe age-associated complications starting in the early developmental period or after the pubertal growth spurt during adolescence, respectively. In addition, patients with HGPS ultimately die of diseases normally seen in the elderly population, with stroke and myocardial infarction as the leading causes of death. Many WS patients develop similar cardiovascular complications but also have an increased predisposition to developing multiple rare malignancies. These premature aging disorders, as well as animal and cell culture models that recapitulate these diseases, have provided insight into the genetics and cellular pathways that underlie these human conditions and have also uncovered possible mechanisms behind normal aging. Here we discuss the history, the types of progeria, and the various pathophysiological mechanisms that drive these diseases. We also address recent medical advances and treatment modalities for patients with progeria.

Association between smoking habits and severity of coronary stenosis as assessed by coronary computed tomography angiography.

Smoking promotes arteriosclerosis and is one of the most important coronary risk factors. However, few studies have investigated the association between smoking habits and the severity of coronary stenosis as assessed by coronary computed tomography angiography (CTA). We enrolled 416 patients [165/251 = smoker (past and current)/non-smoker)]. They had all undergone CTA and either were clinically suspected of having coronary artery disease (CAD) or had at least one cardiovascular risk factor. We divided the patients into smoking and non-smoking groups, and evaluated the presence of CAD, the number of significantly stenosed coronary vessels (VD), and the Gensini score as assessed by CTA in the two groups. The incidence of CAD, VD, the Gensini score, and coronary calcification score in the smoking group were all significantly greater than those in the non-smoking group (CAD, p = 0.009; VD, p = 0.003; Gensini score, p = 0.007; coronary calcification score, p = 0.01). Pack-year was significantly associated with VD and the Gensini score, and was strongly associated with multi-vessel disease (2- and 3-VD) (p < 0.05), whereas the duration of cessation in past smokers was not associated with VD or the Gensini score. Pack-year, but not the duration of cessation, may be the most important factor that was associated with the severity of coronary stenosis in terms of VD and the Gensini score.

A shift to organismal stress resistance in programmed cell death mutants.

Animals have many ways of protecting themselves against stress; for example, they can induce animal-wide, stress-protective pathways and they can kill damaged cells via apoptosis. We have discovered an unexpected regulatory relationship between these two types of stress responses. We find that C. elegans mutations blocking the normal course of programmed cell death and clearance confer animal-wide resistance to a specific set of environmental stressors; namely, ER, heat and osmotic stress. Remarkably, this pattern of stress resistance is induced by mutations that affect cell death in different ways, including ced-3 (cell death defective) mutations, which block programmed cell death, ced-1 and ced-2 mutations, which prevent the engulfment of dying cells, and progranulin (pgrn-1) mutations, which accelerate the clearance of apoptotic cells. Stress resistance conferred by ced and pgrn-1 mutations is not additive and these mutants share altered patterns of gene expression, suggesting that they may act within the same pathway to achieve stress resistance. Together, our findings demonstrate that programmed cell death effectors influence the degree to which C. elegans tolerates environmental stress. While the mechanism is not entirely clear, it is intriguing that animals lacking the ability to efficiently and correctly remove dying cells should switch to a more global animal-wide system of stress resistance.

Association between the severity of coronary artery stenosis and the combination of the difference in blood pressure between arms and brachial-ankle pulse wave velocity.

BACKGROUND: A difference in systolic blood pressure (SBP) ≥10 mmHg between the arms is associated with an increased risk of coronary artery disease (CAD) and mortality in high-risk patients. METHODS AND RESULTS: Four hundred and fourteen patients were divided into three groups according to the percent most severe luminal narrowing of a coronary artery as diagnosed by coronary computed tomography angiography: no or mild coronary stenosis (0-49%), moderate stenosis (50-69%) and severe stenosis (≥70%) groups. The relative difference in SBP between arms in the severe group was significantly lower than those in the no or mild and moderate groups. The brachial-ankle pulse wave velocity (baPWV) significantly increased as the severity of coronary stenosis increased. We confirmed that severe coronary stenosis was independently associated with both the relative difference in SBP between arms and baPWV, in addition to age, gender, hypertension, dyslipidemia, diabetes mellitus and ankle-brachial index by a logistic regression analysis. The group with a relative difference in SBP between arms of <1 mmHg and baPWV ≥ 1613 cm/s showed a higher percentage of patients with severe coronary stenosis than groups that met neither or only one of these criteria. CONCLUSION: The combination of the relative difference in SBP between arms and baPWV may be a more effective approach for the non-invasive assessment of the severity of CAD.

Is pentraxin 3 a biomarker, a player, or both in the context of coronary atherosclerosis and metabolic factors?

The objective of this study is to determine whether pentraxin-3 (PTX-3) is clinically a biomarker of inflammation, a player in anti-inflammation, or both with regard to coronary atherosclerosis, we compared levels of PTX-3 with levels of adiponectin in addition to high-sensitivity C-reactive protein (hs-CRP). We enrolled 693 patients (51 % male; mean age 64 ± 12 years) at Fukuoka University Hospital. They were clinically suspected to have coronary artery disease (CAD) or had at least one cardiac risk factor and had undergone coronary computed tomography angiography (CTA). We evaluated the levels of PTX-3, hs-CRP, and adiponectin, the presence of CAD or metabolic factors, subcutaneous fat area, visceral fat area (VFA) and lipid profiles. The presence of CAD was independently associated with aging (p = 0.010) and the prevalence of hypertension (p < 0.0001), but not the levels of PTX-3, hs-CRP and adiponectin by a multivariate analysis. Although the number of significantly stenosed coronary vessels (VD) was not associated with PTX-3 or adiponectin, hs-CRP tended to increase as the number of VD increased. In addition, PTX-3 decreased as the number of metabolic factors increased, whereas hs-CRP increased as the number of metabolic factors increased. Interestingly, PTX-3 did not correlate with hs-CRP, but was positively correlated with adiponectin. In a multiple regression analysis, adiponectin (p = 0.003) and VFA (p = 0.008) were significant predictors of PTX-3 levels. In conclusion, PTX-3 and adiponectin showed similar associations with metabolic factors, whereas PTX-3 and hs-CRP showed opposite trends. Adiponectin and VFA were significant predictors of PTX-3 levels. PTX-3 might have an atheroprotective role as well as serving as a simple biomarker, like adiponectin.

Topical application of rapamycin ointment ameliorates Dermatophagoides farina body extract-induced atopic dermatitis in NC/Nga mice.

Atopic dermatitis (AD), a chronic inflammatory skin disease characterized by relapsing eczema and intense prurigo, requires effective and safe pharmacological therapy. Recently, rapamycin, an mTOR (mammalian target of rapamycin) inhibitor, has been reported to play a critical role in immune responses and has emerged as an effective immunosuppressive drug. In this study, we assessed whether inhibition of mTOR signalling could suppress dermatitis in mice. Rapamycin was topically applied to inflamed skin in a murine AD model that was developed by repeated topical application of Dermatophagoides farina body (Dfb) extract antigen twice weekly for 7 weeks in NC/Nga mice. The efficacy of topical rapamycin treatment was evaluated immunologically and serologically. Topical application of rapamycin reduced inflammatory cell infiltration in the dermis, alleviated the increase of serum IgE levels and resulted in a significant reduction in clinical skin condition score and marked improvement of histological findings. In addition, increased mTOR phosphorylation in the lesional skin was observed in our murine AD model. Topical application of rapamycin ointment inhibited Dfb antigen-induced dermatitis in NC/Nga mice, promising a new therapy for atopic dermatitis.

Contrast between innovator drug- and generic drug-induced renal dysfunction on coronary angiography (CONTRAST study).

Contrast-induced nephropathy (CIN) has gained increasing attention in clinical practice, particularly during coronary angiography (CAG). However, some "bioequivalent" generic (GE) drugs are less effective than the innovator (IN) drug. Therefore, the aim of this study was to compare contrast media (IN drug)-induced renal dysfunction with contrast media (GE drug)-induced dysfunction. We enrolled 44 patients who underwent elective CAG or percutaneous coronary intervention (PCI) and randomly divided them into two groups that received contrast media (Iohexol, nonionic and low-osmolality contrast agent) containing either IN drug (Omnipaque) or GE drug (Iopaque). Blood and urine sampling were performed before and after (24 and 48 h) CAG or PCI. Biochemical parameters in blood (serum creatinine, cystatin C, high-sensitivity C-reactive protein, and pentraxin-3) and urine (urinary albumin/Cr and liver-type fatty acid binding protein/Cr) were measured. There were no significant differences in the biochemical parameters at baseline between the groups. In addition, there were no differences in changes in biochemical parameters in blood and urine before and after CAG or PCI between the groups, although one patient in the GE group had CIN. The degree of contrast in Iopaque-induced renal dysfunction was comparable with that in Omnipaque-induced dysfunction.

A neurodegenerative disease mutation that accelerates the clearance of apoptotic cells.

Frontotemporal lobar degeneration is a progressive neurodegenerative syndrome that is the second most common cause of early-onset dementia. Mutations in the progranulin gene are a major cause of familial frontotemporal lobar degeneration [Baker M, et al. (2006) Nature 442:916-919 and Cruts M, et al. (2006) Nature 442:920-924]. Although progranulin is involved in wound healing, inflammation, and tumor growth, its role in the nervous system and the mechanism by which insufficient levels result in neurodegeneration are poorly understood [Eriksen and Mackenzie (2008) J Neurochem 104:287-297]. We have characterized the normal function of progranulin in the nematode Caenorhabditis elegans. We found that mutants lacking pgrn-1 appear grossly normal, but exhibit fewer apoptotic cell corpses during development. This reduction in corpse number is not caused by reduced apoptosis, but instead by more rapid clearance of dying cells. Likewise, we found that macrophages cultured from progranulin KO mice displayed enhanced rates of apoptotic-cell phagocytosis. Although most neurodegenerative diseases are thought to be caused by the toxic effects of aggregated proteins, our findings suggest that susceptibility to neurodegeneration may be increased by a change in the kinetics of programmed cell death. We propose that cells that might otherwise recover from damage or injury are destroyed in progranulin mutants, which in turn facilitates disease progression.