Epinephrine in local anesthetic cancels increase in tongue mucosal blood flow after stellate ganglion block in rabbit

The goal of this study was to compare oral mucosal blood flow and duration of anesthetic action after stellate ganglion block (SGB) using lidocaine, with or without epinephrine, and discuss the effect of epinephrine on SGB. Duration of anesthetic action was defined as elapsed time from finish of injection to recovery of common carotid blood flow (CCBF) to within+/-5% of respective control value. Male Japan White rabbits were anesthetized with isoflurane and mechanically ventilated. Common carotid blood flow and tongue mucosal tissue blood flow (TMBF) were measured with an ultrasound flowmeter and laser Doppler flowmeter, respectively. End-tidal partial pressure of carbon dioxide (ETCO(2)) and hemodynamic variables were continuously monitored, including heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP). For SGB, the tip of the needle was placed on the left transverse process of the cervical vertebra, 1-2 mm caudal to the cricoid cartilage. Either 0.1 ml of 1% lidocaine (Group L) or 1% lidocaine containing 10 mug/ml epinephrine (Group LE) was injected for SGB. There were no differences in values at immediately before SGB and at the time when maximal change in CCBF was observed after SGB for ETCO(2), HR, SBP, DBP or MAP in either group. CCBF showed a significant increase in Group L after SGB. In contrast, CCBF only showed a slight increase in Group LE. TMBF showed a significant increase in Group L after SGB, but not in Group LE. No differences in time required for maximal effect were observed between the two groups. In contrast, duration of anesthetic action in Group LE was significantly longer than that in Group L. Addition of epinephrine to local anesthetic solutions is not suitable for SGB, as it may not facilitate an increase in tissue blood flow, which is the primary objective of SGB.     

Spontaneous recurrence of methampetamine psychosis: increased sensitivity to stress associated with noradrenergic hyperactivity and dopaminergic change

We studied the factors precipitating spontaneous recurrences of methamphetamine (MAP)-induced paranoid-hallucinatory states (referred to as “flashbacks”) in 28 flashbackers, along with 18 non-flashbackers with a history of MAP psychosis. Plasma levels of catecholamines and their metabolites were assayed in the 28 flashbackers, the 18 non-flashbackers, 8 subjects with persistent MAP psychosis, and 33 normal controls (22 MAP users and 11 non-users). The flashbackers had been exposed to significantly higher numbers of stressful events, and/or MAP-induced frightening paranoid-hallucinatory states during previous MAP use, than the non-flashbackers. Factors triggering the flashbacks met the DSM-III-R criteria for a mild psychosocial stressor. During flashbacks, plasma norepinephrine levels increased and plasma levels of 3-methoxytyramine, which is an indicator of dopamine release, showed a smaller increase. It follows that stressful experiences together with MAP use may induce sensitization to mild psychosocial stressors. Noradrenergic hyperactivity and some degree of increased dopamine release may be involved in this process. Stress sensitization may elicit memories of MAP psychosis associated with stressful experiences in response to mild psychosocial stressors, leading to the occurrence of flashbacks. Sensitization to stress associated with noradrenergic hyperactivity, involving increased dopamine release may be central to spontaneous recurrences of MAP psychosis. Received: 2 April 1998 / Accepted: 18 February 1999     

Identification and Characteristics of Co-isolation of Multiple Nontuberculous Mycobacteria

Objective Although multiple nontuberculous mycobacteria (NTM) species can be isolated from the same patient, little has been reported on co-isolation. We clarified the trends and characteristics of the co-isolation of multiple NTM species. Methods To collect data on multiple NTM isolation, we first extracted all patients who visited our hospital from 2006 through 2015 with a diagnosis of NTM lung diseases other than Mycobacterium avium complex (MAC) and then reviewed their medical records to evaluate the co-isolation of multiple NTM species. Results Of 213 patients with non-MAC lung disease, the most common NTM species was M. gordonae (32%), followed by M. kansasii (20%) and M. abscessus (14%). Non-MAC NTM lung disease tended to be associated with middle age with a low body mass index and male predominance. Multiple NTM species were isolated from 55 (26%) of the 213 patients. The clinical characteristics associated with multiple NTM species isolation included female predominance, never smokers and the absence of cavity lesions in the lungs. The highest co-isolation rate was observed in patients with M. gordonae isolation (30%), followed by M. furtuitum isolation (26%) and M. abscessus isolation (20%). Only MAC was isolated when co-isolated with M. abscessus. Among M. szulgai, M. peregrinum and M. terrae isolation, no other NTM species were detected. Conclusion Co-isolation of multiple NTM species was not uncommon, with 26% of patients with non-MAC NTM lung diseases showing co-isolation with multiple NTM species. Each NTM species had distinct characteristics in terms of co-isolation.     

Microstructural characterization of polypropene surfaces using grazing incidence X-ray diffraction

The grazing incidence X-ray diffraction was applied for characterizing the crystalline structure of the outermost layer of polypropene sheets. Even in the outermost surface layer within about 5 nm, the crystalline structure of the a form was confirmed by the X-ray diffraction patterns. The values of a and c for the crystal lattice dimension were almost constant in spite of the variation of surface layer crystallinity, whereas the value of b for the surface layer decreased with increasing crystallinity or decreasing comonomer content of polypropene. This suggests that the density of the crystal increased as a function of crystallinity. Additionally, the value of b for the surface layer was smaller than that of the bulk. It was concluded that the lattice distortion can be ascribed to the residual stress caused by the molding pressure under the higher super-cooling rate.     

Modulated degradation of dextran hydrogels grafted with poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) in response to temperature

Dextran hydrogels grafted with poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) were prepared, and their enzymatic degradation was examined at different temperatures. Although swelling ratios for the hydrogels are constant in a wide range of temperature, there is a drop of transmittance of the hydrogels in the swollen state in relation to the lower critical solution temperature of poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide). Temperature-dependent enzymatic degradation was observed in these hydrogels to depend on the molecular weight of the grafts. The degradability of the hydrogel with shorter grafts is independent of temperature. In contrast, the degradability of the hydrogel with longer grafts increases with increasing temperature. Such a modulated degradation of hydrogels is considered to be due to a change in the entanglement between the grafted chain and dextran network by the hydration-dehydration behavior of the grafts.     

Phosphonated mesoporous silica nanoparticles bearing ruthenium complexes used as molecular probes for tracking oxygen levels in cells and tissues

Molecular oxygen plays an important role in living organisms. Its concentration and fluctuation in cells or tissues are related to many diseases. Therefore, there is a need for molecular systems that can be used to detect and quantify oxygen levels in vitro and in vivo. In this study, we synthesized phosphonated mesoporous silica nanoparticles bearing ruthenium complexes in their pores (pM-Rus) and evaluated their photophysical and biological properties. The pM-Rus were highly soluble in water and showed robust phosphorescence under hypoxic conditions, while the addition of oxygen suppressed this emission. Cellular experiments revealed that pM-Rus with a size of 100 nm showed efficient cellular uptake to emit phosphorescence in hypoxic cells. In addition, pM-Rus have negligible toxicity to cells due to the blockage of direct contact between ruthenium complexes and intracellular biomolecules and the deactivation of singlet oxygen (¹O₂) generated by photoexcitation of ruthenium complexes before leaking out of the pores. Animal experiments confirmed that pM-Rus showed robust emission at hypoxic regions in mice. Thus, pM-Rus are promising oxygen probes for living systems.

Phosphonated mesoporous silica nanoparticles bearing ruthenium complexes in their pores were prepared as biocompatible molecular probes to visualize oxygen status in cells and tissues.     

Pan-Asian Consensus on Calcium Hydroxyapatite for Skin Biostimulation,Contouring, and Combination Treatments

BackgroundSeveral usage guidelines for calcium hydroxylapatite (CaHA), a dermal filler material, exist for non-Asian patients, making it necessary to determine whether their findings and consensuses are applicable to Asian patients who have distinct anatomies, cultural preferences, and aesthetic requests.ObjectiveWe sought to develop a Pan-Asian consensus on CaHA use in skin biostimulation, contouring, and combination treatments for face and body indications.MethodsA survey on CaHA usage for contouring and biostimulation indications in Asian patients was conducted, followed by discussions to establish consensus statements and topics for examination.ResultsSeveral aspects of facial shaping and contouring or skin biostimulation with CaHA were agreed on, including that dilution is not a key consideration, that microfocused ultrasound with visualisation precedes CaHA in same day or session treatments, and that cannulas should be used. Among the many agreements on interventions in specific facial and body areas, there were also disagreements due to the diverse Asian patient presentations, requests, and access to tools or products; for example, CaHA should be placed in the interfascial layer for temple contouring, CaHA should not be injected directly into the infraorbital area for safety, and diluted CaHA should be injected subdermally for nonfacial or whole-face biostimulation and contouring.ConclusionOur disagreements highlight the diversity of Asian facial morphotypes and desired aesthetic outcomes and underscore the need for customized aesthetic strategies to accommodate the heterogeneity of Asian anatomies, cultural preferences, and aesthetic ideals. Establishing consensus statements on critical aspects of Asian patient considerations, efficacy and safety, is crucial. This document provides strategic guidance on the use of classic, diluted CaHA for biostimulation or undiluted Radiesse^®(+) (Merz Pharma GmbH & Co. KGaA, Frankfurt, Germany) for lifting and contouring to ensure consistent CaHA delivery for successful patient outcomes.     

Different members of the APOBEC3 family of DNA mutators have opposing associations with the landscape of breast cancer

APOBEC enzymes are strong mutagenic factors. In breast cancer, expression of APOBEC3B is increased and associated with mutation load and poor outcome. Other APOBEC3s can also mutate DNA but their clinical significance in breast cancer and its underpinnings have not been comprehensively studied. In our examination of 1,091 breast carcinoma cases, high expression of APOBEC3A or APOBEC3B genes was associated with greater tumor burden of mutations and other genomic aberrations. Expression of none of the five APOBEC3C-H genes had any correlation with these features, including T[C-T/G]W mutations, but their high expression levels indicated a robust anti-cancer immune response within tumors, with elevated CD8⁺ T cell abundance, T cell receptor diversity, and immune cytolytic activity. Concordantly, survival analyses of this and two other cohorts with > 3,000 patients each showed favorable prognostic benefit of high APOBEC3C-H expression for both cancer progression and mortality. A detrimental prognostic value was observed for APOBEC3A and APOBEC3B. Single-cell data revealed cancer epithelial and stromal immune cells as major sources of APOBEC3B and APOBEC3C-H expression in tumors, respectively. These observations on opposing associations with breast cancer of different APOBEC3s highlight the contrasting roles of these enzymes, promoting cancer through mutagenesis while antagonizing it through immune response.     

Removal of gemcitabine-induced senescent cancer cells by targeting glutaminase1 improves the therapeutic effect in pancreatic ductal adenocarcinoma

Insufficient cancer treatment can induce senescent cancer cell formation and treatment resistance. The characteristics of induced senescent cancer (iSnCa) cells remain unclear. Pancreatic ductal adenocarcinoma (PDAC) has a low and nondurable response rate to current treatments. Our study aimed to analyze the properties of iSnCa cells and the relationship between cellular senescence and prognosis in PDAC. We evaluated the characteristics of gemcitabine-induced senescent cancer cells and the effect of senescence-associated secretory phenotype (SASP) factors released by iSnCa cells on surrounding PDAC cells. The relationship between cellular senescence and the prognosis was investigated in 50 patients with PDAC treated with gemcitabine-based neoadjuvant chemotherapy. Exposure to 5 ng/mL gemcitabine-induced senescence, decreased proliferation and increased senescence-associated β-galactosidase-cell staining without cell death in PDAC cells; the expression of glutaminase1 (GLS1) and SASP factors also increased and caused epithelial-mesenchymal transition in surrounding PDAC cells. iSnCa cells were selectively removed by the GLS1 inhibitor bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES) through apoptosis induction. Cellular senescence was induced in PDAC cells via insufficient gemcitabine in subcutaneous tumor model mice. GLS1 expression was an independent prognostic factor in patients with PDAC who received gemcitabine-based neoadjuvant chemotherapy. This is the first study to identify the relationship between senescence and GLS1 in PDAC. Low-dose gemcitabine-induced senescence and increased GLS1 expression were observed in PDAC cells. Cellular senescence may contribute to treatment resistance of PDAC, hence targeting GLS1 in iSnCa cells may improve the therapeutic effect.