Ketoconazole ion-exchange fiber complex: a novel method to reduce the individual difference of bioavailability in oral administration caused by gastric anacidity

Water insoluble faintly alkaline drugs often have potential absorption problem in gastrointestinal tract in oral administration for patients with gastric anacidity. The purpose of the present study is to develop a novel method to improve the absorption of the water insoluble faintly alkaline drug in peroral administration. This method is based on ion exchange of ion-exchange fibers. Water-insoluble faintly alkaline drug ketoconazole was used as a model drug. Ketoconazole and the active groups of the ion-exchange fibers combined into ion pairs based on the acid-base reaction. This drug carrier did not release drugs in deionized water, but in water solution containing other ions it would release the drugs into the solution by ion exchange. Confirmed by the X-ray diffraction and the differential scanning calorimetry (DSC), the ketoconazole combined onto the ion-exchange fibers was in a highly molecular level dispersed state. The improved dissolution of ketoconazole ion-exchange fiber complexes is likely to originate from this ketoconazole’s highly dispersed state. Furthermore, due to this ketoconazole’s highly dispersed state, ketoconazole ion-exchange fiber complexes significantly decreased the individual difference of absorption in oral administration of ketoconazole caused by the fluctuation of the acid degree in the gastric fluid.     

Comparison between Antegrade versus Retrograde Ureteral Stent Placement for Malignant Ureteral Obstruction

PurposeTo compare the technical success of antegrade uteral stent (AUS) and retrograde ureteral stent (RUS) placements in patients with malignant ureteral obstruction (MUO) and to determine the predictors of technical failure of RUS.Materials and MethodsThis study retrospectively included 61 AUS placements (44 patients) performed under fluoroscopic guidance and 76 RUS placements (55 patients) performed under cystoscopic guidance in patients with MUO from January 2019 to December 2020. Technical success rates of the 2 techniques were compared using inverse probability of treatment weighting (IPTW) analysis. Logistic regression was used to identify predictive factors for technical failures.ResultsTechnical success was achieved in 98.4% of the AUS group and 47.4% of the RUS group. After stabilized IPTW, the technical success rate was higher in the AUS group than in the RUS group (adjusted risk difference, 49.4%; 95% confidence interval [CI], 35.4%–63.1%). The independent predictors for technical failure of the RUS procedure were age of ≥65 years (odds ratio [OR], 5.56; 95% CI, 1.73–21.27), ureteral orifice invasion (OR, 4.21; 95% CI, 1.46–13.46), and extrinsic cancer (OR, 15.58; 95% CI, 2.92–111.81).ConclusionsThe technical success rate of AUS placement was higher than that of RUS placement in patients with MUO. RUS failure was associated with age of ≥65 years, cancer with ureteral orifice invasion, and extrinsic ureteral obstruction.     

Subthalamic nucleus deep brain stimulation improves sleep in Parkinson's disease patients: a retrospective study and a meta-analysis

BackgroundMost Parkinson's patients suffered from sleep problems. There is increasing evidence that Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) has a positive effect on several sleep parameters, improving overall sleep quality in patients with PD. However, the results are controversial.MethodsWe performed a retrospective study and meta-analysis to assess the Parkinson's disease sleep scale (PDSS) in Parkinson's patients.ResultsWe reviewed our data of patients who underwent STN-DBS, and then extracted five other trials to perform a meta-analysis. The pooled results showed an advantage on post-operative PDSS in both our medical center and pooled results (MD = 20.41, 95% CI = [13.03, 27.79], I² = 61%, P < 0.001). There was a significant difference in Unified Parkinson's Disease Rating Scale (UPDRS)-Ⅲ score between pre and post-operation (MD = −12.59, 95% CI = [−14.70, −10.49], I² = 90%, P < 0.001). What's more, Parkinsonian medication was significantly lower in the post-operative groups after DBS (MD = −314.71, 95% CI = [−468.13, −161.28], I² = 53%, P < 0.001).ConclusionIn the retrospective study and meta-analysis of 6 trials, we found that DBS can significantly increase sleep quality. Furthermore, motor function improved and Parkinsonian medication was significantly decreased postoperatively. The sample size was enough and no further investigations would change the conclusion.     

Genicular Artery Embolization for the Treatment of Knee Pain Secondary to Osteoarthritis

PurposeTo evaluate the efficacy and safety of embolization of hyperemic synovial tissue for the treatment of knee pain secondary to osteoarthritis (OA).Materials and MethodsTwenty patients with radiographic knee OA and moderate-to-severe pain refractory to conservative therapy were enrolled in a prospective, 2-site pilot study. Genicular artery embolization (GAE) was performed with 75- or 100-μm spherical particles. Patients were assessed with magnetic resonance imaging at baseline and at 1 month and with the Visual Analogue Scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at baseline and at 1, 3, and 6 months. Adverse events were recorded at all timepoints.ResultsEmbolization of at least 1 genicular artery was achieved in 20/20 (100%) patients. Mean VAS improved from 76 mm ± 14 at baseline to 29 mm ± 27 at 6-month follow-up (P < .01). Mean WOMAC score improved from 61 ± 12 at baseline to 29 ± 27 at 6-month follow-up (P < .01). Self-limiting skin discoloration occurred in 13/20 (65%) patients. Two of 20 (10%) patients developed plantar sensory paresthesia that resolved within 14 days.ConclusionsGAE to treat knee pain secondary to OA can be performed safely and demonstrates potential efficacy. Further randomized comparative studies are needed to determine true treatment effect versus placebo effect.     

Metaplastic Regulation of the Median Raphe Nucleus via Serotonin 5-HT1A Receptor on Hippocampal Synaptic Plasticity Is Associated With Gender-Specific Emotional Expression in Rats

Gender differences in psychiatric disorders are considered to be associated with the serotonergic (5-HTergic) system; however the underlying mechanisms have not been clearly elucidated. In this study, possible involvement of the median raphe nucleus (MRN)-hippocampus 5-HTergic system in gender-specific emotional regulation was investigated, focusing on synaptic plasticity in rats. A behavioral study using a contextual fear conditioning (CFC) paradigm showed that the females exhibited low anxiety-like behavior. Extracellular 5-HT levels in the hippocampus were increased by CFC only in the males. Long-term potentiation (LTP) in the hippocampal CA1 field was suppressed after CFC in the males, which was mimicked by the synaptic response to MRN electrical stimulation. In the MRN, 5-HT immunoreactive cells significantly increased in the females compared with those in the males. Pretreatment with the 5-HT_1A receptor agonists tandospirone (10 mg/kg, i.p.) and 8-OH DPAT (3 mg/kg, i.p.) significantly suppressed LTP induction in the males. Synaptic responses to CFC and 5-HT_1A receptor interventions were not observed in the females. These results suggest that the metaplastic 5-HTergic mechanism via 5-HT_1A receptors in the MRN-hippocampus pathway is a key component for gender-specific emotional regulation and may be a cause of psychiatric disorders associated with vulnerability or resistance to emotional stress.     

A new concept of the contraction–extension property of the left ventricular myocardium

ObjectivesUsing newly developed ultrasonic technology, we attempted to disclose the characteristics of the left ventricular (LV) contraction–extension (C–E) property, which has an important relationship to LV function.MethodsStrain rate (SR) distribution within the posterior wall and interventricular septum was microscopically measured with a high accuracy of 821 μm in spatial resolution by using the phase difference tracking method. The subjects were 10 healthy men (aged 30–50 years).ResultsThe time course of the SR distribution disclosed the characteristic C–E property, i.e. the contraction started from the apex and propagated toward the base on one hand, and from the epicardial side toward the endocardial side on the other hand. Therefore, the contraction of one area and the extension of another area simultaneously appeared through nearly the whole cardiac cycle, with the contracting part positively extending the latter part and vice versa. The time course of these propagations gave rise to the peristalsis and the bellows action of the LV wall, and both contributed to effective LV function.The LV contraction started coinciding in time with the P wave of the electrocardiogram, and the cardiac cycle was composed of 4 phases, including 2 types of transitional phase, as well as the ejection phase and slow filling phase. The sum of the measurement time duration of either the contraction or the extension process occupied nearly equal duration in normal conditions.ConclusionThe newly developed ultrasonic technology revealed that the SR distribution was important in evaluating the C–E property of the LV myocardium. The harmonious succession of the 4 cardiac phases newly identified seemed to be helpful in understanding the mechanism to keep long-lasting pump function of the LV.     

Commutability of external quality assessment materials for serum magnesium and calcium measurements

Abstract

The commutability of pooled patient sera (PPS) and control materials (CM) should be evaluated to investigate their suitability for use in an external quality assessment (EQA) program. Individual human samples, PPS and CM were analyzed by four routine methods and inductively coupled plasma mass spectrometry reference methods for magnesium and calcium measurements. The commutability was analyzed according to EP14-A3 protocol and the difference in bias approach, respectively. For magnesium measurements, all PPS were commutable and 3/5?CM were commutable for all measurement systems according to the EP14-A3 protocol. For calcium measurements, most PPS were commutable for all measurement systems, but the CM were only commutable with the Cobas c702 system. The IFCC approach produced similar commutability profiles, except that a large number of inconclusive results appeared. The routine methods exhibited excellent linearity and precision. The majority of relative biases between the routine and reference methods were beyond the bias limits. The commutability of the CM and PPS vary depending on which evaluation approach and criterion is applied. Superiority in the commutability of PPS over CM was observed whichever evaluation approach is applied.     

采用压差传感器测量医用气体流量的不确定度评定

目的：对采用压差法测量医用气体流量的测量原理、结构和工艺等因素引入的不确定度进行分析.方法：利用液体流经节流装置时所产生的压差测量气体流量.结果：合成不确定度μc=1.364％,满足产品设计要求.结论：压差传感器测量方法准确可靠,能够满足对医用气体流量测量的要求.     

Pravastatin restored the infarct size-limiting effect of ischemic preconditioning blunted by hypercholesterolemia in the rabbit model of myocardial infarction

OBJECTIVES

We tested to find out whether pravastatin restores the infarct size (IS)-limiting effect of ischemic preconditioning (IP) and if it has any effect on the IP-induced activation of adenosine producing enzyme ecto-5′-nucleotidase which plays a key role in the IP-induced cardioprotection.

BACKGROUND

The IS-limiting effect of IP is blunted by hypercholesterolemia. Recently, HMG-CoA reductase inhibitors are shown to have direct cytoprotective effects.

METHODS

Rabbits were fed with a normal or cholesterol (1%) added diet with or without pravastatin (5 mg/kg/day) treatment. Infarct size was measured after 30 min occlusion and 3 h reperfusion of circumflex coronary artery with or without the IP procedure (5 min occlusion and 10 min reperfusion). Additionally, ecto-5′-nucleotidase activities of ischemic and nonischemic myocardium were measured immediately after IP procedure.

RESULTS

This dose of pravastatin did not normalize the increased level of serum cholesterol. The IS-limiting effect of preceding IP (IS reduced from 36.7% to 9.6%, p < 0.001) was abolished by hypercholesterolemia (from 46.1% to 31.3%, p = NS) and restored by pravastatin treatment (from 35.2% to 9.4%, p < 0.001). Pravastatin treatment did not affect IS or the effect of IP under normocholesterolemia. The activation of ecto-5′-nucleotidase presented as the activity ratio of ischemic to nonischemic myocardium (3.1-fold in normocholesterolemia) was blunted by hypercholesterolemia (1.8-fold, p < 0.05) and restored by pravastatin treatment (2.9-fold).

CONCLUSIONS

Pravastatin, at the dose serum cholesterol was not normalized, restored the IS-limiting effect of IP and IP-induced ecto-5′-nucleotidase activation, which were both blunted by hypercholesterolemia. The activation of ecto-5′-nucleotidase may be worth further investigation as a possible mechanism for the hypercholesterolemia-induced retardation and pravastatin-mediated restoration of the cardioprotective effect of IP.     

Patient acceptable symptom state and minimal clinically important difference for patient-reported outcomes in systemic sclerosis: A secondary analysis of a randomized controlled trial comparing personalized physical therapy to usual care

Background

To estimate patient acceptable symptom state (PASS) and minimal clinically important difference (MCID) for patient-reported outcomes in systemic sclerosis (SSc).