The effect of antihistaminic drugs on pentazocine antinociception in the rat

The antinociception produced by pentazocine, diphenhydramine, promethazine, chlorpheniramine, cyclizine and chlorcyclizine in the rat has been measured with a low-temperature (51.5 degrees C) hot-plate from 15 to 75 min following drug administration. The mean reaction times measured at 15 min and the area under the antinociception curves following administration of pentazocine (5 to 30 mg/kg) were linear. Diphenhydramine, chlorpheniramine, promethazine, cyclizine, and chlorcyclizine showed mild antinociceptive potency. The antinociception produced by SC pentazocine (5 and 10 mg/kg) was potentiated, rather than in a simple additive manner, by simultaneous IP administration of 20 mg/kg of diphenhydramine, promethazine, cyclizine, or chlorpheniramine, but not by chlorcyclizine. After concurrent administration of pentazocine and diphenhydramine, diphenhydramine did not alter pentazocine concentrations in the brain and plasma 15 to 75 min following drug administration, nor did pentazocine change diphenhydramine concentrations. Results of this study demonstrate that pentazocine antinociception can be potentiated by several antihistamines and that the potentiation was not due to a mutual effect on metabolism but rather through an as yet undefined mechanism.     

Spinal sagittal malalignment following surgery for primary intramedullary tumours in children.

BACKGROUND/OBJECTIVE: As prior studies analysed predictive factors for various post-laminectomy spinal deformities in mixed spinal regions, age groups or pathologies, their validity and conclusions were unclear. The objective of this study was to determine predictive factors for worsened cervical or thoracic spinal sagittal alignment following laminectomy or laminotomy for primary intramedullary spinal cord tumours in children. METHODS: In this retrospective study, patients treated between 1980 and 1998 were reviewed. Changes in spinal alignment at the last follow-up compared to the pre-operative state were studied. Factors analysed were age, pre-operative spinal alignment, procedure types (laminectomy or laminoplasty), number of laminae operated, surgery of C2 or T1 laminae, histological grade, presence of post-operative neurological deficit and post-operative radiotherapy. RESULTS: There were 27 patients. The mean age was 5.6 years (range 1.3-14.0 years), and the mean duration of follow-up was 3.7 years (range 0.075-9.9 years). In the cervical-cervicothoracic surgical group (n = 12), alignment worsened post-operatively in 3 patients. The number of laminae operated upon had a statistically significant impact on the development of post-operative kyphosis (p = 0.07). In the thoracic-thoracolumbar surgical group (n = 15), alignment worsened in 9 patients. Procedure types were statistically significantly different, with laminectomy associated with an increased risk of post-operative kyphosis (p = 0.01). All 5 patients who had spinal fusion for worsened post-operative alignment were in the thoracic-thoracolumbar group; no patients in the cervical-cervicothoracic group required spinal fusion (p = 0.047). Other predictive factors did not reach statistical significance (p > 0.05). CONCLUSIONS: Worsened spinal sagittal alignment following laminectomy or laminoplasty and the need for spinal fusion is more common in the thoracic-thoracolumbar region than in the cervical-cervicothoracic region. In the cervical-cervicothoracic region, operation on a greater number of laminae tends to increase the risk of worsened alignment. In the thoracic-thoracolumbar region, laminectomy is associated with worsened alignment, while laminoplasty reduces this risk; also, pre-operative kyphotic deformity tends to increase the risk of worsened alignment post-operatively.     

Soybean oil emulsion administration during parenteral nutrition in the preterm infant: effect on essential fatty acid, lipid, and glucose metabolism

To examine the effect of a soybean oil emulsion on essential fatty acid, lipid, and glucose metabolism, preterm infants were randomized to receive 0.5 g/kg/d lipid for 5 days (n = 10, group 1) or 0.5 increased to 2.0 g/kg/d over 5 days (n = 11, group 2). Triene/tetraene ratios did not change in group 1, but decreased in group 2. In both groups, plasma phospholipid linoleate (percent and micrograms per milliliter) increased, the increase being greater in group 2. In both groups, percent content of arachidonate and 5,8,11-eicosatrienoate decreased, and that of oleate remained unchanged. In contrast, absolute content of arachidonate and oleate tended to increase, and that of 5,8,11-eicosatrienoate remained unchanged. At a lipid intake of 0.5 g/kg/d, no infants had hyperlipemia. When lipid intake exceeded 1.0 g/kg/d, the frequency of hypertriglyceridemia (triglycerides greater than 200 mg/dL) and free fatty acidemia, with the free fatty acid/molar albumin ratio exceeding 6:1, increased. Plasma glycerol increased slightly, but was substantially less than the rise in enzymatically determined triglycerides. Hyperglycemia was self-limiting and did not require alteration in dextrose intake. Thus, (1) infusion of a soybean oil emulsion at 0.5 to 2.0 g/kg/d maintains essential fatty acid status and phospholipid arachidonate concentrations; (2) significant hyperlipemia occurs when lipid intake exceeds 1.0 g/kg/d; (3) hyperglycemia associated with lipid infusion tends to be self-limiting and may not require alteration in lipid or dextrose intake; and (4) enzymatically determined triglycerides may be used to monitor lipid tolerance, provided that allowance is made for a small but systematic overestimation resulting from the rise in plasma glycerol.     

Comparative Studies of the Dielectric Properties of Polyester Imide Composite Membranes Containing Hydrophilic and Hydrophobic Mesoporous Silica Particles

In this paper, comparative studies of hydrophilic and hydrophobic mesoporous silica particles (MSPs) on the dielectric properties of their derivative polyester imide (PEI) composite membranes were investigated. A series of hydrophilic and hydrophobic MSPs were synthesized with the base-catalyzed sol-gel process of TEOS, MTMS, and APTES at a distinctive feeding ratio with a non-surfactant template of D-(-)-Fructose as the pore-forming agent. Subsequently, the MSPs were blended with the diamine of APAB, followed by introducing the dianhydride of TAHQ with mechanical stirring for 24 h. The obtained viscous solution was subsequently coated onto a copper foil, 36 μm in thickness, followed by performing thermal imidization at specifically programmed heating. The dielectric constant of the prepared membranes was found to show an obvious trend: PEI containing hydrophilic MSPs > PEI > PEI containing hydrophobic MSPs. Moreover, the higher the loading of hydrophilic MSPs, the higher the value of the dielectric constant and loss tangent. On the contrary, the higher the loading of hydrophobic MSPs, the lower the value of the dielectric constant with an almost unchanged loss tangent.     

Healthy Taiwanese Eating Approach (TEA) toward Total Wellbeing and Healthy Longevity

A healthy dietary pattern review for Asian countries is scarce, which is crucial for guiding healthy eating. We reviewed Taiwanese dietary pattern discovery studies. Included were 19 studies, the majority of which employed dimension reduction methods to find dietary patterns associated with various health conditions. To show what is a high or low intake of foods in Taiwan, we also report the average dietary content and the 25th and 75th percentile values of the adult population for six food groups gathered by the Nutrition and Health Survey in Taiwan, 2017–2020. The healthy Taiwanese dietary approach is cohesive across multiple health outcomes occurring at different ages. It is featured with higher intakes of plant-based foods, aquatic foods, and some beneficial ethnic foods (soy products), drinks (tea), and cooking methods (boiling and steaming); lower intakes of fast foods, fatty and processed meats, sugar, salt rich foods/drinks, and fried foods; but with mixed findings for dairy and egg. Yet, the average Taiwanese person consumed many refined staple foods and livestock, but not sufficient vegetables, fruits, whole grains and roots, beans, and nuts. Dairy consumption remains low. In conclusion, Taiwanese discovery studies point to a mortality-lowering total wellbeing dietary pattern consistent with the current knowledge, which discloses potential benefits of soy product, tea, and boiling and steaming.     

Off-label reduced-dose apixaban does not reduce hemorrhagic risk in Taiwanese patients with nonvalvular atrial fibrillation: A retrospective,observational study

East Asians are reportedly at high risk of anticoagulant-related bleeding; therefore, some physicians prefer to prescribe low-dose direct oral anticoagulants (DOACs). Little is known about the therapeutic effectiveness and safety of off-label reduced-dose apixaban in East Asians with nonvalvular atrial fibrillation (AF). We aimed to investigate the effectiveness and safety of off-label reduced-dose apixaban in Taiwanese patients with nonvalvular AF.This retrospective cohort study enrolled 1073 patients with nonvalvular AF who took apixaban between July 2014 and October 2018 from 4 medical centers in southern Taiwan. The primary outcomes included thromboembolic events (stroke/transient ischemic attack or systemic embolism), major bleeding, and all-cause mortality.Among all patients, 826 (77%) patients were classified as the “per-label adequate-dose” treatment group (i.e., consistent with the Food and Drug Administration label recommendations) while 247 (23%) patients were the “off-label reduced-dose” treatment group. The mean follow-up period was 17.5 ± 13 months. The “off-label reduced-dose” group did not have a lower major bleeding rate than the “per-label adequate-dose” group (4.8% vs 3.8%, adjusted hazard ratio [HR] 1.20, 95% confidence interval [CI] 0.69–2.09), but had a nonsignificantly higher incidence of thromboembolic events (4.23% vs 3.05%, adjusted HR: 1.29, 95% CI: 0.71–2.34).An off-label reduced-dose apixaban treatment strategy may not provide incremental benefits or safety for Taiwanese patients with nonvalvular AF.     

Improved health outcomes in integrative medicine visits may reflect differences in physician and patient behaviors compared to standard medical visits

ObjectiveTo identify differences in patient-physician interactions associated with improvements in GERD symptoms in a randomized controlled trial comparing integrative medicine and primary care/standard visits.MethodsWe analyzed video recordings of 2-minute excerpts (thin slices) from the beginning, middle, and end of 21 study visits (11 standard, 10 integrative medicine).ResultsAccording to blind coders’ analysis of the excerpts, prospective improvement in GERD symptoms was most highly correlated with patients appearing pleased (r = 0.71, p < 0.01) and friendly (r = 0.67, p < 0.01) at the end of the visit, controlling for visit type. The combination of patient and physician smiling at the end of the visit was associated with improvement in GERD symptoms (r² = 0.45, p = 0.004). The physician in the integrative visits was more engaged (p = 0.009), friendly (p = 0.005), relaxed (p = 0.002), smiled longer (p = 0.006), gazed longer (p = 0.02), and gestured more (p = 0.007), compared to standard visits. Patients in integrative visits also smiled longer (p = 0.004).ConclusionThe expanded history-taking questions asked by integrative clinicians may enhance relationship building, modifying patients’ responses and improving patient-centered behaviors from clinicians,ultimately facilitating symptom improvement.Practice ImplicationsAnalysis of nonverbal behaviors may facilitate a better understanding of patient-clinician interactions in integrative medicine visits and yield insights to improve clinical interactions in conventional medicine.     

Evolving potassium channels by means of yeast selection reveals structural elements important for selectivity

Potassium channels are widely distributed. To serve their physiological functions, such as neuronal signaling, control of insulin release, and regulation of heart rate and blood flow, it is essential that K+ channels allow K+ but not the smaller and more abundant Na+ ions to go through. The narrowest part of the channel pore, the selectivity filter formed by backbone carbonyls of the GYG-containing K+ channel signature sequence, approximates the hydration shell of K+ ions. However, the K+ channel signature sequence is not sufficient for K+ selectivity. To identify structural elements important for K+ selectivity, we randomly mutagenized the G protein-coupled inwardly rectifying potassium channel 3.2 (GIRK2) bearing the S177W mutation on the second transmembrane segment. This mutation confers constitutive channel activity but abolishes K+ selectivity and hence the channel's ability to complement the K+ transport deficiency of Deltatrk1Deltatrk2 mutant yeast. S177W-containing GIRK2 mutants that support yeast growth in low-K+ medium contain multiple suppressors, each partially restoring K+ selectivity to S177W-containing double mutants. These suppressors include mutations in the first transmembrane segment and the pore helix, likely exerting long-range actions to restore K+ selectivity, as well as a mutation of a second transmembrane segment residue facing the cytoplasmic half of the pore, below the selectivity filter. Some of these suppressors also affected channel gating (channel open time and opening frequency determined in single-channel analyses), revealing intriguing interplay between ion permeation and channel gating.     

Disposition and metabolic profiles of [14C]viramidine and [14C]ribavirin in rat and monkey red blood cells and liver

The disposition and metabolic profiles of [14C]viramidine and [14C]ribavirin were compared in rat and monkey red blood cells and liver. Our data reveal that the total ribavirin-related components (ribavirin plus its mono-, di-, and triphosphate metabolites) may account for most of the drug in monkey liver following prolonged oral administration of viramidine.