Comparison of factors associated with drooling between intractable neuromuscular disease and cerebral palsy.

Drooling represents a common and noteworthy symptom in patients with intractable neuromuscular disease (IND) and cerebral palsy (CP) and can lead to poor quality of life (QOL) and higher incidence of death due to aspiration of saliva. Identifying the factors affecting drooling is crucial to improving QOL and improving the poor prognosis of patients with IND and CP. This study sought to assess the prevalence of drooling and to elucidate the associated factors, drugs, and differences between patients with IND and CP. We included hospitalized patients with IND and CP. Among the 269 patients, 69 of 162 patients with IND (42.6%) and 75 of 107 patients with CP (70.1%) exhibited drooling. Drooling in IND was significantly higher in patients with tube feeding and those who had a previous stroke than in patients with potential oral intake and those having no history of stroke. In individuals with CP, drooling was significantly negatively associated with age. Taltirelin in patients with IND had a significant positive association with drooling, and antipsychotics and centrally acting muscle relaxants in those with CP had a significant negative association with drooling. Our results suggest that the factors associated with frequent drooling differ between IND and CP cases, and patients who should be screened for drooling are those with decreased swallowing function, those with IND who have had a previous stroke, and young patients with CP. Moreover, clinicians should consider the impact of drugs on drooling in IND and CP cases.

Involvement of sodium-coupled neutral amino acid transporters (system A) in l-proline transport in the rat retinal pericytes.

The retinal pericytes contribute to the supply of collagen to the basement membrane, and thus, form the structural support of the blood-retinal barrier. Since l-proline (L-Pro) is a major component of collagen, the uptake of L-Pro is an important process for the synthesis of collagen. This study was aimed to elucidate L-Pro transport mechanism(s) in the retinal pericytes. The transport of [3H]L-Pro was evaluated in the conditionally immortalized rat retinal pericyte cell line, TR-rPCT1 cells. The expression of the candidate transporter was examined by qualitative/quantitative reverse transcription-polymerase chain reaction, immunoblot analysis, and immunostaining. The [3H]L-Pro uptake by TR-rPCT1 cells showed Na+-dependence, Cl--independence, and concentration-dependence with a Km of 810 µM. The substrates for system A, such as 2-(methylamino)isobutyric acid (MeAIB), significantly inhibited the L-Pro uptake, suggesting the involvement of system A in the uptake of L-Pro. Among the subtypes of system A, the mRNA expression levels of ATA2 were the highest in TR-rPCT1 cells. Immunostaining analysis of the isolated rat retinal capillaries containing pericytes indicated the protein expression of ATA2 in retinal pericytes. In conclusion, it is suggested that ATA2, at least in part, is involved in the transport of L-Pro in the retinal pericytes.

Relationship between Pain and Functional Status in Patients with Amyotrophic Lateral Sclerosis: A Multicenter Cross-Sectional Study.

BACKGROUND: Pain is a widely neglected symptom in patients with amyotrophic lateral sclerosis (ALS), even though it may be common and have a significant impact on the quality of life. OBJECTIVE: The aim of this study was to determine the frequency and characteristics of pain and its treatment in ALS patients. DESIGN: A multicenter cross-sectional study. SETTING/SUBJECTS: Eighty patients with ALS from eight hospitals. MEASUREMENTS: Data on demographics, functional status, and pharmacological treatment were collected. The Barthel Index (BI) was used to assess functional status. Pain was measured using the 0-5-point Wong-Baker FACES Pain Rating Scale. RESULTS: Pain was reported by 53.8% of ALS patients, and 36.3% reported receiving pain medication. Opioids were the drugs most commonly used to treat pain. The differences in pain frequency according to functional status were not statistically significant (p = 0.38). The pain intensity in patients whose functional status was total dependence (BI 0-20, 2.5 ± 1.2) was significantly worse than that in those with better functional status (BI 21-60, 1.4 ± 0.7; BI 61-99, 1.4 ± 0.5; p < 0.01). CONCLUSIONS: Our study indicates that all patients with ALS have the potential to suffer from pain, the intensity of which increases with decreased functional status.

In Vitro Study of L-Glutamate and L-Glutamine Transport in Retinal Pericytes: Involvement of Excitatory Amino Acid Transporter 1 and Alanine-Serine-Cysteine Transporter 2.

L-Glutamate (L-Glu) is known to be a relaxant of pericytes and to induce changes in microcirculatory hemodynamics. Since the concentration of L-Glu which induces the dilation of retinal capillaries is reported to be high compared with the estimated concentration in the retinal interstitial fluid, it is hypothesized that some systems involving concentrative L-Glu release are present in retinal pericytes. The purpose of this study was to investigate the existence of L-Glu-storing systems, which contribute to autocrine L-Glu release, in retinal pericytes using conditionally immortalized rat retinal pericytes (TR-rPCT1 cells), which express mRNAs of L-Glu-synthesizing enzymes from L-glutamine (L-Gln). TR-rPCT1 cells express the mRNAs of vesicular L-Glu transporter 1 (VGLUT1), indicating that L-Glu in the cytoplasm is taken up into VGLUT1-expressing vesicles of retinal pericytes. L-Glu and L-Gln are taken up into TR-rPCT1 cells via Na(+)-dependent saturable process(es) with a Km value of 22.4 µM and 163 µM, respectively. The [(3)H]L-Glu uptake was inhibited by ca. 50% in the presence of D-aspartate, a substrate of excitatory amino acid transporter (EAAT) subtypes, whereas substrates of alanine-serine-cysteine transporter (ASCT) subtypes exhibited only a weak inhibitory effect on [(3)H]L-Glu uptake compared with D-aspartate. Regarding the L-Gln uptake by TR-rPCT1 cells, the inhibitory effect of ASCT substrates on the [(3)H]L-Gln uptake was stronger than that of substrates of other neutral amino acid transport systems. Consequently, it was determined that EAAT1 and ASCT2 play a role in the transport of L-Glu and L-Gln, respectively, from retinal interstitial fluid to the cytoplasm of retinal pericytes.

Involvement of cationic amino acid transporter 1 in L-arginine transport in rat retinal pericytes.

Nitric oxide (NO), a known relaxant, is produced in cells from L-arginine (L-Arg). Because the relaxation of retinal pericytes alters the microcirculatory hemodynamics, it is important to understand the manner of NO production in retinal pericytes. The purpose of this study was to clarify the molecular mechanism(s) of uptake of L-Arg in retinal pericytes using a conditionally immortalized rat retinal pericyte cell line (TR-rPCT1 cells) which expresses the mRNAs of endothelial NO synthase and inducible NO synthase. L-Arg uptake by TR-rPCT1 cells exhibited Na(+)-independence and concentration-dependence with a Km of 28.9 µM. This process was strongly inhibited by substrates of cationic amino acid transporters (CAT), such as L-ornithine and L-lysine. In contrast, L-valine, L-leucine, and L-glutamine, which are substrates of cation/neutral amino acid transport systems, such as system y(+)L, system B(0,+), and system b(0,+), did not strongly inhibit L-Arg uptake by TR-rPCT1 cells. In addition, the expression of mRNA and protein of CAT1 in TR-rPCT1 cells was observed by reverse transcription-polymerase chain reaction and immunoblot analyses. Taking these results into consideration, it appears that CAT1 is involved in L-Arg uptake by retinal pericytes and this is expected to play an important role in the relaxation of retinal pericytes, thereby modulating the microcirculatory hemodynamics in the retina.