Injury of the alveolar epithelium by cigarette smoke is presumed to be an important process in the pathogenesis of smoking-related pulmonary diseases. We investigated the cytotoxic effects of cigarette smoke extract (CSE) on an alveolar type II cell-derived cell line (A549). CSE caused apoptosis at concentrations of 5% or less and necrosis at 10% or more. When CSE was exposed to air before application to A549 cells, the cytotoxic effects were attenuated. CSE caused cell death without direct contact with the cells. Acrolein and hydrogen peroxide, two major volatile factors in cigarette smoke, caused cell death in a similar manner. Aldehyde dehydrogenase, a scavenger of aldehydes, and N-acetylcysteine, a scavenger of oxidants and aldehydes, completely inhibited CSE-induced apoptosis. CSE and acrolein increased intracellular oxidant activity. In conclusion, apoptosis of alveolar epithelial cells may be one of the mechanisms of lung injury induced by cigarette smoking. This cytotoxic effect might be due to an interaction between aldehydes and oxidants present in CSE or formed in CSE-exposed cells.

Aim Up to 60% of depressed patients do not obtain sufficient relief from a course of antidepressant therapy, and these treatment-resistant major depressive disorder (TRD) patients are at increased risk for relapse, chronicity, persistent psychosocial impairments, and suicide. Probiotics actively participate in treatment of neuropsychiatric disorders. However, the role of gut microbiota in brain disorders and depression remains unclear. We performed a prospective study to evaluate the effects of Clostridium butyricum MIYAIRI 588 (CBM588). Methods This was an 8-week open-label study to evaluate the efficacy and safety of CBM588 in combination with antidepressants in adult patients diagnosed with TRD according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Forty antidepressant-treated inpatients were included. Patients were randomized to adjuvant treatment with CBM588 (n = 20) or control (n = 20). The primary endpoint was the change in the 17-item Hamilton Depression Rating Scale score from baseline to week 8. Secondary end points were changes in the Beck Depression Inventory and the Beck Anxiety Inventory scale scores from baseline to week 8. The Systematic Assessment of Treatment Emergent Events—General Inquiry was used to assess adverse effects. Results CBM588 (60 mg/d) in combination with antidepressants (flvoxamine, paroxetine, escitalopram, duroxetine, and sertraline) provided significant improvement in depression. All patients completed the trial, and 70% responded to treatment; the remission rate was 35.0%. No serious adverse events occurred. Conclusions These preliminary data suggest that CBM588 in combination with antidepressants is effective and well tolerated in the treatment of TRD. Further studies using a larger, double-blind, parallel-group design are warranted to confirm these findings.

Recent developments on Heusler alloys including Ni–Mn–X and Ni–Co–Mn–X (X = Ga, In, Sn,…) demonstrate multiferroic phase transformations with large abrupt changes in lattice parameters of several percent and corresponding abrupt changes in ferromagnetic ordering near the transition temperatures. These materials enable a new generation of thermomagnetic generators that convert heat to electricity within a small temperature difference below 5 K. While thermodynamic calculations on this energy conversion method predict a power density normalized to material volume of up to 300 mW cm−3, experimental results have been in the range of µW cm−3. Challenges are related to the development of materials with bulk‐like single‐crystal properties as well as geometries with large surface‐to‐volume ratio for rapid heat exchange. This study demonstrates efficient thermomagnetic generation via resonant actuation of freely movable thin‐film devices of the Heusler alloy Ni–Mn–Ga with unprecedented power density of 118 mW cm−3 that compares favorably with the best thermoelectric generators. Due to the large temperature‐dependent change of magnetization of the films, a periodic temperature change of only 3 K is required for operation. The duration of thermomagnetic duty cycle is only about 12 ms, which matches with the period of oscillatory motion.

Abstract. Benidipine is a dihydropyridine-derived calcium channel blocker developed in Japan, with several unique mechanisms of action, that is, triple calcium channels (L, N, and T) blocking action with a membrane approach. Benidipine has relatively high vascular selectivity and is expected to show protective effects on vascular endothelial cells. Renal protective effects of benidipine also have been shown in several basic and clinical studies. Moreover, anti-oxidative action and enhancing nitric oxide production have been noted with this drug, following its cardioprotective effects in patients with ischemic heart diseases. In fact, benidipine exerted a better prognostic effect than other calcium channel blockers in the therapy for patients with vasospastic angina. In addition, benidipine showed reliable antihypertensive, renoprotective effects if used in combination with angiotensin II type 1 receptor blockers (ARBs) when adequate anti-hypertensive effects are not achieved by ARBs alone, indicating that benidipine is an useful calcium channel blocker in combination therapy for hypertension. Benidipine was launched on the Japanese market 14 years ago, but few severe side effects have been reported, suggesting that this is a drug with established safety and long-acting pharmacological effects.

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optical, medical and lab-on-chip systems including mobile, wearable and implantable devices. [ 5 ] Various concepts for energy harvesting on a miniature scale have been developed in the past based, e.g., on piezoelectric, [ 1,6 ] electromagnetic induction, [ 7 ] electrostatic, [ 8 ] and thermoelectric principles. [ 9 ] In the fi rst three cases, kinetic energy is generated by using vibration in the environment. These systems are commonly based on electromechanically coupled spring-damper systems.Thermoelectric principles use temperature gradients in the environment to produce electrical power (Seebeck effect). In contrast to the aforementioned principles, no moving parts are required. While being versatile for various applications, they face a number of diffi culties when it comes to miniaturization. The effi ciency of thermoelectric devices is determined by the fi gure of merit ZT , which is in the order of 1 in best cases. [ 10 ] In order to obtain a reasonable output, relatively large temperature differences Δ T and means of heat sinking beyond natural convection are required. [ 11 ] In small dimensions, however, Δ T is reduced and, thus, energy conversion becomes ineffi cient.For the use of energy resources stored at small Δ T below 20 K, smart materials showing a fi rst order phase transformation without diffusion are highly attractive. Recent developments on MSMAs demonstrate abrupt changes in lattice parameters beyond 10% and corresponding large changes in their magnetic properties (magnetization, magnetic anisotropy) at small Δ T . [12][13][14][15][16][17] Owing to their multifunctional properties, these materials may perform different tasks while keeping the design simple, which is important for downscaling. Due to these reasons, magnetic SMAs are predestined for thermal microenergy harvesting.Recently, a new series of magnetic SMA systems, Ni-Mn-X-Y (X: In, Sn, Sb, Y: Co, Fe) has been found showing a fi rst order phase transformation with a large change of magnetization Δ M . [14][15][16][17] Ni-Mn-In and Ni-Co-Mn-In alloys show a particularly drastic Δ M effect due to a martensitic transition from a ferromagnetic austenite phase to a nonferromagnetic martensite phase. [ 18,19 ] An important prerequisite for energy conversion in a cyclic process are highly reversible phase transformations. The stress associated with the change of lattice parameters during phase transformation can cause pronounced microstructural changes including the formation of dislocations and other A new method for thermal energy harvesting at small temperature difference and high cycling frequency is presented that exploits the unique magnetic properties and actuation capability of magnetic shape memory alloy (MSMA) fi lms. Polycrystalline fi lms of the Ni 50.4 Co 3.7 Mn 32.8 In 13.1 alloy are tailored, showing a large abrupt change of magnetization and low thermal hysteresis well above room temperature. Based on this material, a free-standing fi lm device is designed that exhibits thermomagnetically induced actuation between a hea...

Magnetocaloric properties of a Ni 50 Mn 36 Co 1 Sn 13 ferromagnetic shape memory alloy have been studied experimentally in the vicinity of a first-order magnetostructural phase-transition low-temperature paramagnetic martensite↔ high-temperature ferromagnetic austenite. The magnetic entropy change ⌬S m calculated from the magnetization M͑T͒ data measured upon cooling is higher than that estimated from M͑T͒ measured upon heating. Contrary to ⌬S m , the adiabatic temperature change ⌬T ad measured upon cooling is significantly smaller than that measured upon heating. The apparent discrepancy between ⌬S m and ⌬T ad ͑larger ⌬S m , smaller ⌬T ad upon cooling, and smaller ⌬S m , larger ⌬T ad upon heating͒ is caused by the hysteretical behavior of this magnetostructural transition, a feature common for all the alloys in the family of Ni 50 Mn 25+x Z 25−x ͑Z =In,Sn,Sb͒ ferromagnetic shape memory Heusler compounds. The hysteresis causes the magnetocaloric parameters to depend strongly on the temperature and field history of the experimental processes.

The Heck-type olefination and carbonylation of a binaphthaleneiodonium salt 1 in the presence of a palladium catalyst gave high yields of the corresponding 2-iodo-2'-functionalized-1,1'-binaphthyls with high selectivity.