Interstitial lung changes and persistent COVID-19 in a patient with follicular lymphoma: A case report.

We herein report a case of interstitial lung changes in a patient with prolonged coronavirus disease 2019 (COVID-19) with follicular lymphoma receiving rituximab and bendamustine who recovered after treatment with a combination therapy consisting of corticosteroids and immunosuppressive agents. There is currently no treatment strategy for prolonged pneumonitis following COVID-19, which can be life-threatening for immunocompromised patients. Thus, further investigation is warranted.

Involvement of γ-aminobutyric acid transporter 2 in the hepatic uptake of taurine in rats.

Taurine is essential for the hepatic synthesis of bile salts and, although taurine is synthesized mainly in pericentral hepatocytes, taurine and taurine-conjugated bile acids are abundant in periportal hepatocytes. One possible explanation for this discrepancy is that the active supply of taurine to hepatocytes from the blood stream is a key regulatory factor. The purpose of the present study is to investigate and identify the transporter responsible for taurine uptake by periportal hepatocytes. An in vivo bolus injection of [(3)H]taurine into the rat portal vein demonstrated that 25% of the injected [(3)H]taurine was taken up by the liver on a single pass. The in vivo uptake was significantly inhibited by GABA, taurine, ß-alanine, and nipecotic acid, a GABA transporter (GAT) inhibitor, each at a concentration of 10 mM. The characteristics of Na(+)- and Cl(-)-dependent [(3)H]taurine uptake by freshly isolated rat hepatocytes were consistent with those of GAT2 (solute carrier SLC6A13). Indeed, the K(m) value of the saturable uptake (594 µM) was close to that of mouse SLC6A13-mediated taurine transport. Although GABA, taurine, and ß-alanine inhibited the [(3)H]taurine uptake by > 50%, each at a concentration of 10 mM, GABA caused a marked inhibition with an IC(50) value of 95 µM. The [(3)H]taurine uptake exhibited a significant reduction when the GAT2 gene was silenced. Immunohistochemical analysis showed that GAT2 was localized on the sinusoidal membrane of the hepatocytes predominantly in the periportal region. These results suggest that GAT2 is responsible for taurine transport from the circulating blood to hepatocytes predominantly in the periportal region.

Accurate and highly reproducible picoliter injection system for capillary electrophoresis.

A novel, highly accurate sample injection system for capillary electrophoresis (CE) was developed based on an inkjet microchip capable of reproducing exact introduction volumes at the picoliter level. The difficulty in analyte discrimination using electrokinetic injection was also overcome using this injection method. The injection system consisted of an XY stage, an inkjet droplet ejection microchip, and a reservoir with a plug-in septum. To evaluate the precision of the system, a mixture of NBD-labeled amino acids consisting of Gly, L-Phe, L-Asp, and L-Ser was separated, and the performance was compared with that of traditional hydrodynamic and electrokinetic injection methods. The results demonstrated that the introduced volume highly relied on the number of droplets with low relative standard derivation (RSD) and good linear correction coefficient in the proposed injection method. In addition, a urine sample was analyzed via CE coupled with the inkjet injection system for the detection of the amino acid taurine. The concentration of urinary taurine was determined to be 2.42 ± 0.08 µM (confidence level, 95%; RSD, 1.05%; n = 4) with a recovery of 98.92-109.54% (n = 3). These results demonstrate the inkjet injection system we developed has the potential to revolutionize capillary electrophoretic separation in practical and commercial applications that require an automated accurate injection system.

Lysophospholipids enhance taurine release from rat retinal vascular endothelial cells under hypoosmotic stress.

Sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) are simple bioactive lysophospholipids which exhibit an effect on blood vessels via their G protein-coupled receptors. The purpose of this study was (i) to clarify the impact of S1P and LPA on the release of taurine as an organic osmolyte from rat retinal vascular endothelial cells (RVECs) under hypoosmotic stress and (ii) to quantify the gene expression levels of S1P and LPA receptors in RVECs. When cultured RVECs (TR-iBRB2 cells) that had been preloaded with [(3)H]taurine were exposed to hypotonic buffer (230 mOsm) for 1 to 10 min, [(3)H]taurine release from the cells was several times greater than that using an isotonic buffer (300 mOsm). S1P and LPA significantly enhanced the [(3)H]taurine release under hypotonic conditions in a time- and concentration-dependent manner, whereas S1P and LPA had no significant effect under isotonic conditions. Quantitative real-time PCR revealed that freshly isolated RVECs predominantly express mRNAs for S1P(1), S1P(4) and LPA(4). The S1P-enhanced [(3)H]taurine release under hypoosmotic conditions was significantly inhibited by an S1P(1) receptor antagonist. Inhibitor of the small GTPase Rho, C3 exotoxin, attenuated S1P- and LPA-enhanced [(3)H]taurine release. These results suggest that S1P and LPA play a novel role in the regulation of osmolyte efflux from RVECs in response to hypoosmotic stress via the activation of their specific receptors.

Efficacy of Tape Feedback Therapy on Synkinesis Following Severe Peripheral Facial Nerve Palsy.

BACKGROUND: Mirror feedback rehabilitation is effective in preventing the development of oro-ocular synkinesis following severe facial palsy. However, we do not have effective maneuvers to prevent the deterioration of oculo-oral synkinesis. We developed a new method of biofeedback rehabilitation using tape for the prevention of oculo-oral synkinesis. OBJECTIVE: The aim of the present study was to investigate the efficacy of taping feedback rehabilitation. METHODS: Twelve consecutive patients with peripheral facial nerve palsy who developed synkinesis were divided into 2 groups. Six patients were treated with the new training method, and the remaining 6 patients were treated with conventional therapy as controls. In the experiment group, tape was placed around the mouth, and the patient was instructed to close the eyes so that no movements of the mouth would be perceived from sensations of the taped skin. After 4 weeks of training, facial movements were recorded and movie images were graded for mouth synkinesis using the revised Sunnybrook facial grading system by examiners blinded to patient grouping. RESULTS: Mouth corner contraction during eye closure was significantly weaker in the experimental group than in the control group. CONCLUSIONS: Our new feedback method could help prevent the deterioration of oculo-oral synkinesis.

Fermented Brown Rice and Rice Bran with Aspergillus oryzae (FBRA) Prevents Inflammation-Related Carcinogenesis in Mice, through Inhibition of Inflammatory Cell Infiltration.

We have established an inflammation-related carcinogenesis model in mouse, in which regressive QR-32 cells subcutaneously co-implanted with a foreign body-gelatin sponge-convert themselves into lethal tumors due to massive infiltration of inflammatory cells into the sponge. Animals were fed with a diet containing 5% or 10% fermented brown rice and rice bran with Aspergillus oryzae (FBRA). In 5% and 10% FBRA diet groups, tumor incidences were lower (35% and 20%, respectively) than in the non-treated group (70%). We found that FBRA reduced the number of inflammatory cells infiltrating into the sponge. FBRA administration did not cause myelosuppression, which indicated that the anti-inflammatory effects of FBRA took place at the inflammatory lesion. FBRA did not have antitumor effects on the implanted QRsP-11 tumor cells, which is a tumorigenic cell line established from a tumor arisen after co-implantation of QR-32 cells with sponge. FBRA did not reduce formation of 8-hydroxy-2'-deoxyguanine adducts, a marker of oxidative DNA damage in the inflammatory lesion; however, it reduced expression of inflammation-related genes such as TNF-α, Mac-1, CCL3 and CXCL2. These results suggest that FBRA will be an effective chemopreventive agent against inflammation-related carcinogenesis that acts by inhibiting inflammatory cell infiltration into inflammatory lesions.

Involvement of orexin-A neurons but not melanin-concentrating hormone neurons in the short-term regulation of food intake in rats.

In order to elucidate the involvement of melanin-concentrating hormone (MCH) and orexin-A (ORX-A) neurons of the perifornical/lateral hypothalamic areas (PF/LH) in the regulation of food intake induced by acutely reduced glucose availability, we examined the food intake response and c-Fos expression in the MCH and ORX-A neurons in the PF/LH during 2-deoxy-D-glucose (2DG)-induced glucoprivation (400 mg/kg; i.v.) and systemic insulin-induced hypoglycemia (5 U/kg; s.c.) in male Wistar rats. The administration of both 2DG and insulin stimulated food intake and induced c-Fos expression in the ORX-A neurons corresponding to food intake, but not in the MCH neurons. These data indicate that ORX-A neurons, but not MCH neurons, play a role in the short-term regulation of food intake, and that the input signals for the neurons containing MCH and ORX-A are different, and these neurons play different roles in the regulation of feeding behavior.

γ-Aminobutyric acid transporter 2 mediates the hepatic uptake of guanidinoacetate, the creatine biosynthetic precursor, in rats.

Guanidinoacetic acid (GAA) is the biosynthetic precursor of creatine which is involved in storage and transmission of phosphate-bound energy. Hepatocytes readily convert GAA to creatine, raising the possibility that the active uptake of GAA by hepatocytes is a regulatory factor. The purpose of this study is to investigate and identify the transporter responsible for GAA uptake by hepatocytes. The characteristics of [(14)C]GAA uptake by hepatocytes were elucidated using the in vivo liver uptake method, freshly isolated rat hepatocytes, an expression system of Xenopus laevis oocytes, gene knockdown, and an immunohistochemical technique. In vivo injection of [(14)C]GAA into the rat femoral vein and portal vein results in the rapid uptake of [(14)C]GAA by the liver. The uptake was markedly inhibited by γ-aminobutyric acid (GABA) and nipecotinic acid, an inhibitor of GABA transporters (GATs). The characteristics of Na(+)- and Cl(-)-dependent [(14)C]GAA uptake by freshly isolated rat hepatocytes were consistent with those of GAT2. The Km value of the GAA uptake (134 µM) was close to that of GAT2-mediated GAA transport (78.9 µM). GABA caused a marked inhibition with an IC(50) value of 8.81 µM. The [(14)C]GAA uptake exhibited a significant reduction corresponding to the reduction in GAT2 protein expression. GAT2 was localized on the sinusoidal membrane of the hepatocytes predominantly in the periportal region. This distribution pattern was consistent with that of the creatine biosynthetic enzyme, S-adenosylmethionine:guanidinoacetate N-methyltransferase. GAT2 makes a major contribution to the sinusoidal GAA uptake by periportal hepatocytes, thus regulating creatine biosynthesis in the liver.