Measurement of the leak rate of masks used for anticancer drug handling using a mask fitting tester.

BACKGROUND: Exposure to inhalation of anticancer drugs is frequent in anticancer drug handling. Using an activated carbon mask with the ability to remove particulates and vapors of anticancer drugs may be effective. Mask fitting performance is important, because low fitting performance leads to inhalation via bypassing the mask filter (leak). This study evaluated the leak rate of multiple-shaped masks. METHODS: Activated carbon and nonactivated carbon masks of the pleated-type (like surgical mask) and cup-type were used. Four pharmacists wore the masks and a fitting tester was employed. The particle reduction rate of particles in ambient air was calculated using: particle count (outside - inside)/outside × 100 (%). Leak rate was calculated as the difference in the particle reduction rate due to the presence or the absence of a seal in the mask surroundings. RESULTS: Reduction rates of the pleated-type nonactivated carbon mask and the pleated-type activated carbon mask were 14.8% and 34.8% (mean). These values significantly increased to 85.6% and 83.3% upon sealing the mask surroundings. Particle reduction rates of the cup-type nonactivated carbon mask and activated carbon mask were 99.3% and 33.6%. When mask surroundings were sealed, these values were 99.6% and 39.2%. Leak rates of pleated-type nonactivated carbon mask, pleated-type activated carbon mask, cup-type nonactivated carbon mask, and cup-type activated carbon mask were 70.8%, 48.5%, 0.3%, and 5.6%, respectively. CONCLUSION: A difference was found in the leak rate between masks used in anticancer drug handling. Based on the low leak rate, the cup-type activated carbon mask was thought to be effective.

Effectiveness of a pharmaceutical instruction video for adherence to dermatopathy treatment in patients with cancer receiving the anti-epidermal growth factor receptor antibody.

BACKGROUND: Dermatopathy develops as a side effect in patients receiving anti-epidermal growth factor receptor antibody treatment. Topical moisturizers are used for the prevention and treatment of this dermatopathy. Active participation of patients in their own treatment is important for the appropriate application of topical preparations. We prepared a pharmaceutical instructional video for adhering to the topical application protocol. In this study, we investigated the effectiveness of this pharmaceutical instructional video on treatment adherence. METHODS: Study participants were patients with cancer receiving the anti-epidermal growth factor receptor antibody for the first time. A pharmacist instructed the patients on how to use the pharmaceutical instruction video. Daily topical preparation use following the video demonstration was assessed. The effectiveness of the pharmaceutical instruction video was evaluated by assessing the adherence of patients who did not use the pharmaceutical instruction video for the past 2 periods (26 months; controls 1 and 2). The incidence of side effects was compared between the two control groups and the group of patients who received the pharmaceutical instruction video. RESULTS: The amount of topical preparation consumed (median, g/day) by patients who received patient compliance instructions using the pharmaceutical instruction video was 9.8 g/day, as compared with control group 1 (4.5 g/day) and control group 2 (5.5 g/day) (p < 0.001). There was no difference in the incidence of side effects during the three periods. CONCLUSION: The use of visual instructional media for patient compliance by pharmacists may be effective in maintaining and improving treatment adherence.

Adherence to a topical moisturizing preparation for regorafenib-related hand-foot skin reaction.

OBJECTIVE: Application of topical moisturizing preparations is important for the prevention and palliation of hand-foot skin reaction induced by multi-kinase inhibitor. Application adherence of topical moisturizing preparations in clinical practice has rarely been reported. This study investigated the factors affecting adherence to the application of topical moisturizing preparations in patients administered regorafenib. METHODS: The subjects were patients administered regorafenib (n = 118). Consumption of a urea-based moisturizing ointment, hand-foot skin reaction grade (CTC-AE ver 3.0), treatment duration, and dose of regorafenib, factors that might affect the onset of symptoms and adherence, including age, sex, presence of a key person, working status, performance status, past use of capecitabine or epidermal growth factor receptor antibodies, and relative dose intensity were retrospectively investigated. The adherence to the topical moisturizing ointment (<21 g per week) was judged as poor. The data were analyzed by logistic regression analysis. RESULTS: Working status was associated with poor adherence, showing a positive correlation (odds ratio; 3.024, p = 0.023). In contrast, symptom grade of hand-foot skin reaction and regorafenib relative dose intensity showed negative correlation with poor adherence (odds ratio; 0.971, p = 0.012, and 0.485, p < 0.001, respectively). CONCLUSIONS: The results suggest that adherence decreases in patients with working. The relative dose intensity of regorafenib decreased when adherence to topical moisturizing ointments decreased. Severe hand-foot skin reaction could be associated with adherence. Patients consciously might not apply the ointment when hand-foot skin reaction did not become severe. It will be problematic for medical personnel to motivate patients for improving adherence to the use of moisturizing ointments.

Microglia-triggered hypoexcitability plasticity of pyramidal neurons in the rat medial prefrontal cortex.

Lipopolysaccharide (LPS), an outer component of Gram-negative bacteria, induces a strong response of innate immunity via microglia, which triggers a modulation of the intrinsic excitability of neurons. However, it is unclear whether the modulation of neurophysiological properties is similar among neurons. Here, we found the hypoexcitability of layer 5 (L5) pyramidal neurons after exposure to LPS in the medial prefrontal cortex (mPFC) of juvenile rats. We recorded the firing frequency of L5 pyramidal neurons long-lastingly under in vitro whole-cell patch-clamp, and we found a reduction of the firing frequency after applying LPS. A decrease in the intrinsic excitability against LPS-exposure was also found in L2/3 pyramidal neurons but not in fast-spiking interneurons. The decrease in the excitability by immune-activation was underlain by increased activity of small-conductance Ca2+-activated K+ channels (SK channels) in the pyramidal neurons and tumor necrosis factor (TNF)-α released from microglia. We revealed that the reduction of the firing frequency of L5 pyramidal neurons was dependent on intraneuronal Ca2+ and PP2B. These results suggest the hypoexcitability of pyramidal neurons caused by the upregulation of SK channels via Ca2+-dependent phosphatase during acute inflammation in the mPFC. Such a mechanism is in contrast to that of cerebellar Purkinje cells, in which immune activation induces hyperexcitability via downregulation of SK channels. Further, a decrease in the frequency of spontaneous inhibitory synaptic transmission reflected network hypoactivity. Therefore, our results suggest that the directionality of the intrinsic plasticity by microglia is not consistent, depending on the brain region and the cell type.

A Destruction Model of the Vascular and Lymphatic Systems in the Emergence of Psychiatric Symptoms.

The lymphatic system is important for antigen presentation and immune surveillance. The lymphatic system in the brain was originally introduced by Giovanni Mascagni in 1787, while the rediscovery of it by Jonathan Kipnis and Kari Kustaa Alitalo now opens the door for a new interpretation of neurological diseases and therapeutic applications. The glymphatic system for the exchanges of cerebrospinal fluid (CSF) and interstitial fluid (ISF) is associated with the blood-brain barrier (BBB), which is involved in the maintenance of immune privilege and homeostasis in the brain. Recent notions from studies of postmortem brains and clinical studies of neurodegenerative diseases, infection, and cerebral hemorrhage, implied that the breakdown of those barrier systems and infiltration of activated immune cells disrupt the function of both neurons and glia in the parenchyma (e.g., modulation of neurophysiological properties and maturation of myelination), which causes the abnormality in the functional connectivity of the entire brain network. Due to the vulnerability, such dysfunction may occur in developing brains as well as in senile or neurodegenerative diseases and may raise the risk of emergence of psychosis symptoms. Here, we introduce this hypothesis with a series of studies and cellular mechanisms.

Differential regulation of the sphere formation and maintenance of cancer-initiating cells of malignant mesothelioma via CD44 and ALK4 signaling pathways.

Malignant mesothelioma (MM) has a poor prognosis and is largely resistant to standard treatments, so it is important to seek novel therapeutic strategies for this disease. Cancer-initiating cells (CICs) were previously identified in MM using stem cell-associated markers in combination with spheroid cultures. However, the mechanisms underlying the induction and maintenance of CICs in MM remain to be fully explored. Here we showed that the CICs, which had high aldehyde dehydrogenase levels (ALDHbright) and stem cell-associated genes, were expanded in MM cells cultured under sphere-forming conditions. The MM spheroids also initiated tumors in immunodeficient mice more efficiently than did conventional adherent MM cells. In the MM spheroids, the expression of hyaluronan (HA) synthases was upregulated. Inhibiting the HA synthesis or CD44 functions by gene knockdown or neutralizing antibody abolished the formation of large-sized spheroids and the expansion of ALDHbright CICs. The expression of activin-A was also increased in the spheroids, and type I activin-A receptor subunit (ALK4) was upregulated in the ALDHbright CICs. The neutralization of activin-A or functional inactivation of ALK4 diminished the ALDHbright CICs without affecting spheroid formation. The knockdown of CD44 or ALK4 strongly suppressed the tumor growth in immunodeficient mice. These results together suggest that the HA-CD44 and activin-A-ALK4 pathways differentially regulate the spheroid formation and maintenance of ALDHbright CICs in MM cells, and that both pathways play critical roles in tumor growth in immunodeficient hosts. Our findings provide a novel therapeutic option for MM that targets signaling pathways that promote the CIC compartment through CD44 and ALK4.