Solid-State Generation of Diarylisonaphthofuran and Its Mechanochemical Diels-Alder Reaction with Epoxynaphthalene.

Invited for the cover of this issue are Toshiyuki Hamura and co-workers at Kwansei Gakuin University. The image depicts solid-state generation of diarylisonaphthofuran from 1,3-diaryl-1,3-dihydronaphthofuranol and its mechanochemical Diels-Alder reaction with epoxynaphthalene. Read the full text of the article at 10.1002/chem.202302660.

Solid-State Generation of Diarylisonaphthofuran and Its Mechanochemical Diels-Alder Reaction with Epoxynaphthalene.

A solid-state method was developed for generating diarylisonaphthofurans from 1,3-diaryl-1,3-dihydronaphthofuranols. The generated reactive molecules were stable in the solid state and could be stored without any extra precautions. X-ray diffraction analysis revealed a typical quinoidal structure. Furthermore, the mechanochemical Diels-Alder reaction of 1,3-diarylisonaphthofurans with epoxynaphthalenes afforded synthetically attractive diepoxypentacenes.

A Case of Significant Improvement of Heart Failure With Reduced Ejection Fraction With a Small Dose of Candesartan in a Hemodialysis Patient With Hypertensive Heart Disease and Nephrosclerosis.

Hypertension induces vascular damage followed by organ damage, including heart failure in hypertensive heart disease (HHD) and nephrosclerosis (the resultant renal pathologic change from long-standing hypertension affecting renal vascular supply), ultimately causing renal failure. Renin-angiotensin-aldosterone system (RAAS) inhibitors are well known as effective drugs for the treatment of hypertension and the anti-remodeling of affected organs. A 52-year-old male was evaluated. Right atrophic kidney and proteinuria were noted in his high school years; however, he had no symptoms for about 35 years. He had pollakiuria in November and oliguria and leg edema in December 2020. The edema deteriorated rapidly, and general fatigue and orthopnea emerged in January 2021. Anasarca, hypertension (198/151 mmHg), tachycardia (115/minute), and hypoxemia (oxygen saturation {SpO2} of 93%) were observed on admission. A bilateral pleural effusion and pulmonary congestion were found on a chest X-ray (CXR) examination. An echocardiogram showed a 22% left ventricle ejection fraction (LVEF). Blood urea nitrogen (BUN) and serum creatinine concentrations were 70 mg/dL and 6.05 mg/dL, respectively. He was diagnosed with nephrosclerosis and HHD-induced cardiac exhaustion. Hemodialysis was started in April 2021. Even though the dry weight was decreased by draining water, cardiomegaly (cardiothoracic ratio {CTR}: 60%), low LVEF (20%-30%), and hypertension, especially diastolic hypertension (140-150/100-120 mmHg), were sustained. After 2 mg of candesartan was added in November 2021, the cardiomegaly, blood pressure (BP), and LVEF were rapidly ameliorated. The CTR and LVEF recovered to 48.5% and 60%, respectively, in April 2022. Statistical analyses showed that the independent factors for CTR were the mean monthly diastolic BP (standard partial regression coefficient {[Formula: see text]}: 0.9058, p<0.0001) and candesartan ([Formula: see text]: -0.7389, p=0.0011) in vital signs and prescribed drugs, respectively. We experienced a case of a significant effect of candesartan treatment against heart failure with reduced ejection fraction (HFrEF) caused by HHD in a hemodialysis patient with nephrosclerosis. Statistical analyses suggested that the improvement of HFrEF resistant to fluid removal by hemodialysis was presumably due to a decrease in diastolic BP caused by a small dose of candesartan.

Effects of Reducing L-Carnitine Supplementation on Carnitine Kinetics and Cardiac Function in Hemodialysis Patients: A Multicenter, Single-Blind, Placebo-Controlled, Randomized Clinical Trial.

L-carnitine (LC) supplementation improves cardiac function in hemodialysis (HD) patients. However, whether reducing LC supplementation affects carnitine kinetics and cardiac function in HD patients treated with LC remains unclear. Fifty-nine HD patients previously treated with intravenous LC 1000 mg per HD session (three times weekly) were allocated to three groups: LC injection three times weekly, once weekly, and placebo, and prospectively followed up for six months. Carnitine fractions were assessed by enzyme cycling methods. Plasma and red blood cell (RBC) acylcarnitines were profiled using tandem mass spectrometry. Cardiac function was evaluated using echocardiography and plasma B-type natriuretic peptide (BNP) levels. Reducing LC administration to once weekly significantly decreased plasma carnitine fractions and RBC-free carnitine levels during the study period, which were further decreased in the placebo group (p < 0.001). Plasma BNP levels were significantly elevated in the placebo group (p = 0.03). Furthermore, changes in RBC (C16 + C18:1)/C2 acylcarnitine ratio were positively correlated with changes in plasma BNP levels (ß = 0.389, p = 0.005). Reducing LC administration for six months significantly decreased both plasma and RBC carnitine levels, while the full termination of LC increased plasma BNP levels; however, it did not influence cardiac function in HD patients.

Fluorescent Ferroelectrics of Hydrogen-Bonded Pyrene Derivatives.

Organic materials with diverse molecular designs show multifunctional properties such as coupled ferroelectric, optical, ferromagnetic, and transport properties. We report the design of an alkylamide-substituted pyrene derivative displaying fluorescent ferroelectric properties coupled with electron transport properties. In solution phase, this compound displayed concentration-dependent fluorescence, whereas in xerogels, a fluorescent green organogel (>0.1 mM) and entangled nanofibers were observed. A discotic hexagonal columnar liquid crystalline phase was observed above 295 K due to intermolecular hydrogen bonding and π-stacking interactions. The direction of the hydrogen-bonded chains could be inverted by the application of an external electric field along the π-stacked column, resulting in ferroelectric polarization-electric field (P-E) hysteresis. The local electric field arising from the ferroelectric macrodipole moment arrangement along the π-stacking direction affected the electron transport properties on the π-stack of pyrenes, thus confirming the current-switching phenomena according to P-E hysteresis. We report that multifunctional properties such as ferroelectricity, fluorescence, and electron transport switching were successfully achieved in hydrogen-bonded dynamic π-molecular assemblies.

Oral L-carnitine supplementation increases trimethylamine-N-oxide but reduces markers of vascular injury in hemodialysis patients.

OBJECTIVES: Food or supplement-derived L-carnitine is changed to trimethylamine (TMA) by interstinal microbiota, which is further metabolized to trimethylamine-N-oxide (TMAO), being involved in the promotion of atherosclerosis in animal models. Meanwhile, carnitine deficiency has played a role in accelerated atherosclerosis in hemodialysis (HD) patients. However, effects of oral L-carnitine supplementation on circulating levels of TMAO and markers of vascular injury and oxidative stress in patients on HD remain unclear. In this study, we addressed the issue. METHODS: Thirty-one HD patients with carnitine deficiency were treated with oral L-carnitine (900 mg/d) for 6 months. At baseline and after treatment, clinical variables including circulating levels of carnitine fractions, TMA, TMAO, advanced glycation end products (AGE), soluble forms of intracellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and malondialdehyde (MDA) were measured. RESULTS: Oral L-carnitine supplementation significantly increased total, free, acyl carnitine, and plasma TMA and TMAO levels, whereas it decreased markers of vascular injury and oxidative stress such as sICAM-1, sVCAM-1, and MDA levels. TMA and TMAO levels at baseline were correlated with each other, and free carnitine was independently associated with TMAO levels. Furthermore, change in AGE values from baseline ([INCREMENT]AGE) was positively correlated with [INCREMENT]sICAM-1 (P = 0.043) and was a sole independent determinant of [INCREMENT]sICAM-1 (R = 0.133, P = 0.043). CONCLUSIONS: This study demonstrated that although oral L-carnitine supplementation was associated with increased TMAO levels, it might be beneficial on vascular injury in patients on HD. Vasculoprotective properties of L-carnitine supplementation in HD patients might be ascribed partly to its inhibitory actions on AGE.

Carnitine deficiency is associated with late-onset hypogonadism and depression in uremic men with hemodialysis.

Late-onset hypogonadism (LOH) and depression contribute to cardiovascular disease (CVD) in male hemodialysis (HD) patients. Carnitine deficiency is frequently observed in HD patients, playing a role in CVD. We examined whether carnitine deficiency was independently associated with LOH and depression in these patients. Twenty-six male HD patients underwent determinations of serum levels of free carnitine and testosterone. Status of LOH and depression were evaluated by questionnaires using aging male symptoms' (AMS) scale and self-rating depression scale (SDS), respectively. Free carnitine and testosterone levels in male HD patients were significantly lower than those in age-matched healthy male subjects. Linear regression analysis showed that AMS scale was positively associated with SDS. Univariate regression analysis revealed that total carnitine (inversely), free carnitine (inversely) and HD duration were correlated with AMS scale. Multiple stepwise regression analysis revealed that free carnitine was an independent determinant of AMS scale. Furthermore, free carnitine was also independently correlated with SDS in male HD patients. This study demonstrated that decreased free carnitine levels were independently associated with AMS scale and SDS in male HD patients. The observations suggest that decreased free carnitine levels could be a marker and therapeutic target of LOH and depression in uremic men with HD.

Effects of switching from calcium carbonate to lanthanum carbonate on bone mineral metabolism in hemodialysis patients.

Phosphate binders are useful for the treatment of hyperphosphatemia in hemodialysis (HD) patients. This study was performed to examine the effects of switching from calcium carbonate (CC) to lanthanum carbonate (LC) on bone mineral metabolism and inflammatory markers in HD patients. We conducted 29 stable HD patients receiving CC, which was replaced by LC and followed-up for 12 weeks. Patients underwent determinants of blood chemistries such as serum calcium (Ca), phosphorus, parathyroid hormone (PTH) and vitamin D status, and interleukin-6 (IL-6) mRNA levels in whole blood cells were evaluated by real-time PCR just before and after the treatment with LC. Corrected Ca [corrected] levels were significantly reduced, but serum phosphorus levels (P levels) were unchanged after LC treatment. Switching to LC increased whole-PTH, osteocalcin, 1,25(OH)(2) D(3) levels and 1,25(OH)(2) D(3)/25(OH)D(3) ratio. 1,25(OH)(2) D(3)/25(OH)D(3) ratio was negatively correlated with HD duration. Furthermore, whole blood cell IL-6 mRNA levels were significantly reduced by LC treatment. We provided that the switching from CC to LC improved Ca overload and ameliorated vitamin D and inflammatory status in HD patients. These observations suggest that LC may play a protective role for the progression of atherosclerosis and vascular calcification in these patients.