Adenosine 5'-triphosphate (ATP) is an extracellular signal that regulates various cellular functions. Cellular secretory activities are enhanced by ATP as well as by cholinergic and adrenergic stimuli. The present study aimed to determine which purinoceptors play a role in ATP-induced changes in the intracellular concentration of calcium ions ([Ca²⁺](i)) and in the fine structure of acinar cells of rat lacrimal glands. ATP induced exocytotic structures, vacuolation and an increase in [Ca²⁺](i) in acinar cells. The removal of extracellular Ca²⁺ or the use of Ca²⁺ channel blockers partially inhibited the ATP-induced [Ca²⁺](i) increase. U73122 (an antagonist of PLC) and heparin (an antagonist of IP₃ receptors) did not completely inhibit the ATP-induced [Ca²⁺](i) increase. P1 purinoceptor agonists did not induce any changes in [Ca²⁺](i), whereas suramin (an antagonist of P2 receptors) completely inhibited ATP-induced changes in [Ca²⁺](i). A P2Y receptor agonist, 2-MeSATP, induced a strong increase in [Ca²⁺](i), although UTP (a P2Y₂,₄,₆ receptor agonist) had no effect, and reactive blue 2 (a P2Y receptor antagonist) resulted in partial inhibition. The potency order of ATP analogs (2-MeSATP > ATP >>> UTP) suggested that P2Y₁ played a significant role in the cellular response to ATP. BzATP (a P2X₇ receptor agonist) induced a small increase in [Ca²⁺](i), but α,β-meATP (a P2X₁,₃ receptor agonist) had no effect. RT-PCR indicated that P2X₂,₃,₄,₅,₆,₇ and P2Y₁,₂,₄,₁₂,₁₄ are expressed in acinar cells. In conclusion, the response of acinar cells to ATP is mediated by P2Y (especially P2Y₁) as well as by P2X purinoceptors.
Phosphonium ylide catalysis through an oxidative quenching cycle has been developed for visible-light-driven C−H imidation of arenes and heteroarenes. The present protocol could be applied not only to trihalomethylative lactonization reactions involving trifluoromethyl, trichloromethyl, and tribromomethyl radicals but also to the first example of an organophotoredoxcatalyzed imidative lactonization reaction involving a nitrogencentered electrophilic radical species.
Various factors, including spinal deformities and trunk muscle atrophy, greatly affect the fall risk among older adults with lumbar spinal stenosis (LSS). However, the etiology of falls in older adults with degenerative LSS and trunk muscle atrophy is poorly understood. We investigated the association between trunk muscle atrophy and falls in older LSS patients. This retrospective study included 99 hospitalized older adults with LSS. Participants completed self-reported fall score questionnaires and were divided into the fall risk (n = 30) and non-fall risk (n = 69) groups. The patients’ low back pain visual analog scale score, Geriatric Depression Scale score, sagittal vertical axis, L4/5 lumbar multifidus cross-sectional area ratio (LMCSAR), and center of pressure (COP) values during quiet standing were evaluated. The fall risk group had a lower L4/5 LMCSAR (p = 0.002) and increased COP excursion (p = 0.034) than the non-fall risk group. No significant differences were observed in the other measured variables between the two groups. The L4/5 LMCSAR (p < 0.001) and COP (p = 0.024) were related to fall risk and may be useful in fall risk assessment in such populations. Strategies aimed at enhancing controlled lumbar segmental motion and improving trunk muscle stability or mass may decrease the fall risk in this cohort.
Protease-activated receptors (PARs) represent a novel class of seven transmembrane domain G-protein coupled receptors, which are activated by proteolytic cleavage. PARs are present in a variety of cells and have been prominently implicated in the regulation of a number of vital functions. Here, lacrimal gland acinar cell responses to PAR activation were examined, with special reference to intracellular Ca(2+) concentration ([Ca(2+)]i) dynamics. In the present study, detection of acinar cell mRNA specific to known PAR subtypes was determined by reverse transcriptase polymerase chain reaction. Only PAR2 mRNA was detected in acinar cells of lacrimal glands. Both trypsin and a PAR2-activating peptide (PAR2-AP), SLIGRL-NH2, induced an increase in [Ca(2+)]i in acinar cells. The removal of extracellular Ca(2+) and the use of Ca(2+) channel blockers did not inhibit PAR2-AP-induced [Ca(2+)]i increases. Furthermore, U73122 and xestospongin C failed to inhibit PAR2-induced increases in [Ca(2+)]i. The origin of the calcium influx observed after activated PAR2-induced Ca(2+) release from intracellular Ca(2+) stores was also evaluated. The NO donor, GEA 3162, mimicked the effects of PAR2 in activating non-capacitative calcium entry (NCCE). However, both calyculin A (100 nM) and a low concentration of Gd(3+) (5 μM) did not completely block the PAR2-AP-induced increase in [Ca(2+)]i. These findings indicated that PAR2 activation resulted primarily in Ca(2+) mobilization from intracellular Ca(2+) stores and that PAR2-mediated [Ca(2+)]i changes were mainly independent of IP3. RT-PCR indicated that TRPC 1, 3 and 6, which play a role in CCE and NCCE, are expressed in acinar cells. We suggest that PAR2-AP differentially regulates both NCCE and CCE, predominantly NCCE. Finally, our results suggested that PAR2 may function as a key receptor in calcium-related cell homeostasis under pathophysiological conditions such as tissue injury or inflammation.
To clarify the factors deciding the advisability of outdoor activities for community-dwelling stroke patients. [Subjects] Sixty-five hemiplegic stroke outpatients of our hospital with a stroke onset of less than 6 months. [Methods] Based on the life space assessment (LSA) of maximum independent activity range, subjects were divided into an indoor group and an outdoor group, and the results of the 10-m walking time (10mWT), the 6-min walking distance (6MWD), the 30-s sit-to-stand count, and the 30-s chair-stand test (CS-30) of each group were compared. Furthermore, when significant differences were found, the cutoff points were calculated. [Results] Significant differences were found for the 10mWT, the 6MWD, and the CS-30. Their respective cutoff points were 22.9 s, 112 m, and 5.5 times. [Conclusion] The results suggest the advisability of outdoor activities can be determined using the 10mWT, 6MWD and CS-30.
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