No abstract

The endothelin (ET) family of peptides acts via two subtypes of guanine nucleotide-binding regulatory protein (G protein)-coupled receptors termed ETA and ETB. ET-1 stimulated cAMP formation in Chinese hamster ovary (CHO) cells stably expressing human wild-type ETA (CHO/hETA cells) while it inhibited cAMP formation in CHO cells expressing human wild-type ETB (CHO/hETB cells), and pharmacological evidence indicated that the opposite effects were due to the selective coupling of each receptor subtype with G alpha s/G alpha i. To find out a receptor domain(s) that determined the selective coupling, a series of chimeric receptors between hETA and hETB was expressed on CHO cells, and the effect of ET-1 on cAMP formation in each cell line was tested. hETA with the replacement of second and/or third intracellular loop (ICLII and/or -III) to the corresponding region(s) of hETB failed to transmit the stimulatory effect of ET-1. hETB with the replacement of ICLIII to the corresponding region of hETA failed to transmit the inhibitory effect of ET-1. A chimeric receptor with ICLII of hETB and with ICLIII of hETA failed to transmit both effects. In cells expressing chimeric receptors with ICLII of hETA and with ICLIII of hETB, ET-1 inhibited cAMP formation while it stimulated cAMP formation when cells were pretreated with pertussis toxin. These results indicated the roles of ICLII and -III of hETR as a major determinant of the selective coupling of hETA and hETB with G alpha s/G alpha i, respectively. We also demonstrated that each receptor subtype expressed on the same cell could work independently, i.e. for hETA to activate G alpha s and for hETB to activate G alpha i, resulting in dose-dependent dual effects of ET-1 on cAMP formation.

We describe a consecutive series of 26 patients with simple bone cysts who were treated by curettage, multiple drilling and continuous decompression by the insertion of either a cannulated screw or a pin. In the first 15 patients we used titanium cannulated screws (group 1) and in the next 11 a cannulated hydroxyapatite pin (group 2). Satisfactory healing was achieved in 12 patients in group 1 (80%) and in all in group 2. This technique seems to be a promising option for the treatment of simple bone cysts. The cannulated hydroxyapatite pin is recommended because of its higher success rate and the fact that it does not need to be removed.

IMPORTANCEThe optimal management for acute traumatic cervical spinal cord injury (SCI) is unknown. OBJECTIVE To determine whether early surgical decompression results in better motor recovery than delayed surgical treatment in patients with acute traumatic incomplete cervical SCI associated with preexisting canal stenosis but without bone injury. DESIGN, SETTING, AND PARTICIPANTSThis multicenter randomized clinical trial was conducted in 43 tertiary referral centers in Japan from December 2011 through November 2019. Patients aged 20 to 79 years with motor-incomplete cervical SCI with preexisting canal stenosis (American Spinal Injury Association [ASIA] Impairment Scale C; without fracture or dislocation) were included. Data were analyzed from September to November 2020. INTERVENTIONS Patients were randomized to undergo surgical treatment within 24 hours after admission or delayed surgical treatment after at least 2 weeks of conservative treatment. MAIN OUTCOMES AND MEASURES The primary end points were improvement in the mean ASIA motor score, total score of the spinal cord independence measure, and the proportion of patients able to walk independently at 1 year after injury. RESULTS Among 72 randomized patients, 70 patients (mean [SD] age, 65.1 [9.4] years; age range, 41-79 years; 5 [7%] women and 65 [93%] men) were included in the full analysis population (37 patients assigned to early surgical treatment and 33 patients assigned to delayed surgical treatment).Of these, 56 patients (80%) had data available for at least 1 primary outcome at 1 year. There was no significant difference among primary end points for the early surgical treatment group compared with the delayed surgical treatment group (mean [SD] change in ASIA motor score, 53.7 [14.7] vs 48.5 [19.1]; difference, 5.2; 95% CI, −4.2 to 14.5; P = .27; mean [SD] SCIM total score, 77.9 [22.7] vs 71.3 [27.3]; P = .34; able to walk independently, 21 of 30 patients [70.0%] vs 16 of 26 patients [61.5%]; P = .51). A mixed-design analysis of variance revealed a significant difference in the mean change in ASIA motor scores between the groups (F 1,49 = 4.80; P = .03). The early surgical treatment group, compared with the delayed surgical treatment group, had greater motor scores than the delayed surgical treatment group at 2 weeks (mean [SD] score, 34.2 [18.8] vs 18.9 [20.9]), 3 months (mean [SD] score, 49.1 [15.1] vs 37.2 [20.9]), and 6 months (mean [SD] score, 51.5 [13.9] vs 41.3 [23.4]) after injury. Adverse events were common in both groups (eg, worsening of paralysis, 6 patients vs 6 patients; death, 3 patients vs 3 patients).

The effects of a water extract prepared from the leaves of Salacia reticulata on the absorption of sugars in normal and type 1 diabetic mice were investigated. The simultaneous oral administration of the extract at a dose of 1.0 mg/mouse with maltose or sucrose inhibited the postprandial elevation of the plasma glucose and insulin levels and intestinal alpha-glucosidase activities in mice. In addition, the supply of a 0.01% solution of the extract as drinking water prevented the elevation of the plasma glucose level and intestinal alpha-glucosidase activities in type 1 diabetic mice. This treatment also prevented the elevation of the plasma, pancreatic, and kidney lipid peroxide levels, lowering of the plasma insulin level, and elevation of the kidney aldose reductase activities in diabetic mice. These results suggest that the water extract of the leaves of S. reticulata could be a beneficial food material for the prevention of diabetes and obesity because of its multiple effects.