Hybrid ubiquinone: novel inhibitor of mitochondrial complex I

AbstractWe synthesized novel ubiquinone analogs by hybridizing the natural ubiquinone ring (2,3-dimethoxy-5-methyl-1,4-benzoquinone) and hydrophobic phenoxybenzamide unit, and named them hybrid ubiquinones (HUs). The HUs worked as electron transfer substrates with bovine heart mitochondrial succinate–ubiquinone oxidoreductase (complex II) and ubiquinol–cytochrome c oxidoreductase (complex III), but not with NADH–ubiquinone oxidoreductase (complex I). With complex I, they acted as inhibitors in a noncompetitive manner against exogenous short-chain ubiquinones irrespective of the presence of the natural ubiquinone ring. Elongation of the distance between the ubiquinone ring and the phenoxybenzamide unit did not recover the electron accepting activity. The structure/activity study showed that high structural specificity of the phenoxybenzamide moiety is required to act as a potent inhibitor of complex I. These findings indicate that binding of the HUs to complex I is mainly decided by some specific interaction of the phenoxybenzamide moiety with the enzyme. It is of interest that an analogous bulky and hydrophobic substructure can be commonly found in recently registered synthetic pesticides the action site of which is mitochondrial complex I

Videofluoroscopy-guided balloon dilatation for treatment of severe pharyngeal dysphagia

Balloon dilatation is a widely accepted technique in the management of esophageal and other types of gastrointestinal strictures, but it is rarely used for the treatment of pharyngeal dysphagia. Therefore, the aim of our prospective study was to evaluate the use of videofluoroscopy-guided balloon dilatation (VGBD) for the treatment of severe pharyngeal dysphagia. The study included 32 stroke patients who had been diagnosed with oral and/or pharyngeal dysphagia. All patients underwent dilatation of the esophageal inlet using a balloon catheter under videofluoroscopic guidance during one or more sessions. Following esophageal dilatation, manual feeding was provided twice weekly. VGBD was effective in 10 out of 32 patients; however, the remaining 22 patients were unable to attempt oral food consumption because aspiration was not completely resolved on videofluoroscopy. According to this case series, VGBD may provide treatment for patients with severe pharyngeal dysphagia, who have not consumed food orally for a long period of tim

Development and evaluation of automated ultrasonographic detection of bladder diameter for estimation of bladder urine volume

Bladder urine volume has been estimated using an ellipsoid method based on triaxial measurements of the bladder extrapolated from two-dimensional ultrasound images. This study aimed to automate this process and to determine the accuracy of the automated estimation method for normal and small amounts of urine. A training set of 81 pairs of transverse and longitudinal ultrasound images were collected from healthy volunteers on a tablet-type ultrasound device, and an automatic detection tool was developed using them. The tool was evaluated using paired transverse/longitudinal ultrasound images from 27 other healthy volunteers. After imaging, the participants voided and their urine volume was measured. For determining accuracy, regression coefficients were calculated between estimated bladder volume and urine volume. Further, sensitivity and specificity for 50 and 100 ml bladder volume thresholds were evaluated. Data from 50 procedures were included. The regression coefficient was very similar between the automatic estimation (β = 0.99, R2 = 0.96) and manual estimation (β = 1.05, R2 = 0.97) methods. The sensitivity and specificity of the automatic estimation method were 88.5% and 100.0%, respectively, for 100 ml and were 94.1% and 100.0%, respectively, for 50 ml. The newly-developed automated tool accurately and reliably estimated bladder volume at two different volume thresholds of approximately 50 ml and 100 ml

Color doppler ultrasonography to evaluate hypoechoic areas in pressure ulcers: A report of two cases

Ultrasound (US) is frequently used for evaluating inflammation of subcutaneous tissue caused by pressure ulcers (PUs), but color Doppler mode (CDM) helps to better identify inflammatory edema in subcutaneous fat and necrotic tissue in PUs. We report two cases where inflammatory edema in subcutaneous fat and necrotic tissue in PUs are identified using small US equipment with CDM. Case 1 – An 82-year-old male presented with cerebral infarction and a Category III PU in the sacral region. B-mode gray-scale US imaging (B-mode imaging) revealed a thickened layer of subcutaneous fat with fat lobules and homogeneous cobblestone appearance with fluid accumulation within the echo-free space. CDM did not identify any color signal (CS) in hypoechoic areas. Case 2 – A 29-year-old female presented with cytopenia and decreased renal function with a Category IV PU with undermining in the coccyx region. B-mode imaging distinguished the necrotic tissue, indicating a diffuse hypoechoic area with no layers, unclear borders, and uneven gray level (cloud-like image) in the subcutaneous fat. Similar B-mode imaging findings were obtained in inflammatory edema with cobblestone appearance. CDM did not detect a CS in the hypoechoic areas but confirmed peripheral hypervascularity. CDM imaging identified inflammatory edema in the subcutaneous fat and necrotic tissue in PUs. Specifically, CDM may better evaluate early-stage PUs with necrotic tissue by distinguishing necrosis from intense inflammatory edema

A Randomized Controlled Trial to Investigate the Effectiveness of the Prevention of Aspiration Pneumonia Using Recommendations for Swallowing Care Guided by Ultrasound Examination

Prevention for aspiration pneumonia requires assessment of aspiration and adequate swallowing care. This randomized controlled trial aimed to investigate the effectiveness of ultrasound examination and recommendations for swallowing care for the reduction of aspiration and pharyngeal post-swallow residue as compared with standard swallowing care. Twenty-three participants were randomized to the intervention group and 23 to the control group. The intervention consisted of four ultrasound examinations during mealtimes and recommendations for swallowing care every 2 weeks during an 8 week period. No recommendations concerning swallowing care based on ultrasound examinations were provided to the control group. The frequency of aspiration or residue was defined as x/y × 100% when aspiration or residue were detected x times from y times concerning the total ultrasound measurements. The proportion of the residents with reduced frequency of aspiration which was detected by ultrasonography at eight weeks were 4.3% in the intervention group and 0% in the control group. The median reduction in the frequency of aspiration and residue in the intervention group was 31%, and that in the control group was 11%. In conclusion, swallowing care guided by frequent ultrasound examinations during mealtimes had a trend of reducing the frequency of aspiration and residue during an 8-week period in individuals relative to standard swallowing care alone

Fecal Distribution Changes Using Colorectal Ultrasonography in Older People with Physical and Cognitive Impairment Living in Long-Term Care Facilities: A Longitudinal Observational Study

Nurses encounter difficulties evaluating constipation in elderly people with physical and cognitive impairment. Transabdominal ultrasonography (US) has been used to evaluate fecal impaction or fecal quality. However, it is unclear whether colorectal US can evaluate constipation symptoms in older people. Using colorectal US, we continuously observed the elderly and clarified the relationship between patterns of fecal distribution changes and constipation symptoms in older people with physical and cognitive impairment at long-term care facilities. This study included patients aged ≥65 years with oral intake. US was performed once a day until the next defecation, and fecal hardness was assessed. US images were extracted and categorized. Then, patterns of fecal distribution changes in the colorectum were classified. Multiple logistic regression analysis was performed to examine related factors associated with a constipation pattern. Among 101 patients, US images of 95 patients were analyzed. In 74.4% of the patients, US showed continuation of reflection with acoustic shadow in the rectum, which was significantly associated with defecation on the bed. Of the patients with a continuous crescent-shaped reflection pattern (R3), 92.9% had hard stool. R3 was found to be significantly associated with a Mini-Mental State Examination score of ≤10. In most of the patients, US detected a continuation of reflection with acoustic shadow in rectal patterns, indicating fecal retention in the rectum. Point-of-care US can be used by nurses to visualize rectal fecal retention as constipation patterns in the older people with physical and cognitive impairment at long-term care facilities