Perturbations of Telmisartan Alone and in Combination with Ranolazineor Dapagliflozin on the Amplitude and Gating of Voltage-gated Na+ Current in Neuroblastoma Neuronal Cells.

ABSTRACT: A recent study investigated the correlation between telmisartan (TEL) exposure and Alzheimer's disease (AD) risk among African Americans (AAs) and European Americans. Their findings indicated that moderate-to-high TEL exposure was linked to a decreased incidence of AD among AAs. These results suggest a potential association between TEL and a reduced risk of AD specifically within the AA population. Here, we investigated the effects of TEL, either alone or in combination with ranolazine (Ran) or dapagliflozin (Dapa), on voltage-gated Na+ currents (INa) in Neuro-2a cells. TEL, primarily used for treating hypertension and cardiovascular disorders, showed a stimulatory effect on INa, while Ran and Dapa reversed this stimulation. In Neuro-2a cells, we demonstrated that with exposure to TEL, the transient (INa(T)) and late (INa(L)) components of INa were differentially stimulated with effective EC50's of 16.9 and 3.1 µM, respectively. The research implies that TEL's impact on INa might be associated with enhanced neuronal excitability. This study highlights the complex interplay between TEL, Ran, and Dapa on INa and their potential implications for AD, emphasizing the need for further investigation to understand the mechanisms involved.

Minimally Invasive Resection of a Foraminal Lumbar Root Schwannoma.

Background and Importance: This video article reports a rare case of a right L5/S1 foraminal root schwannoma that presents the natural course of the disease, imaging findings, treatment protocol, operative procedure, and highlights some of the possible surgical complications. Clinical Presentation: Magnetic resonance imaging (MRI) revealed an intradural, extramedullary, well-enhanced mass at the right L5/S1 level. The operative procedure involved a right minimal L5/S1 laminotomy/foraminotomy posteriorly to open the right L5 root. The facet joints were preserved to prevent spinal instability. The tumor was located along the root after opening the right L5/S1 foramen. Intraoperative electromyography (IOM) was conducted to detect any nerve injury in the patient. After opening the dura, the tumor was carefully separated from the normal root nerve under IOM monitoring. The mass was removed piece-by-piece using mini-forceps. Conclusion: Histopathological examination confirmed the diagnosis of a schwannoma. The patient recovered without incident after surgery with minimal soreness and numbness in the right leg.

Novel Aptamer-Based Small-Molecule Drug Screening Assay to Identify Potential Sclerostin Inhibitors against Osteoporosis.

A novel aptamer-based competitive drug screening platform for osteoporosis was devised in which fluorescence-labeled, sclerostin-specific aptamers compete with compounds from selected chemical libraries for the binding of immobilized recombinant human sclerostin to achieve high-throughput screening for potential small-molecule sclerostin inhibitors and to facilitate drug repurposing and drug discovery. Of the 96 selected inhibitors and FDA-approved drugs, six were shown to result in a significant decrease in the fluorescence intensity of the aptamer, suggesting a higher affinity toward sclerostin compared with that of the aptamer. The targets of these potential sclerostin inhibitors were correlated to lipid or bone metabolism, and several of the compounds have already been shown to be potential osteogenic activators, indicating that the aptamer-based competitive drug screening assay offered a potentially reliable strategy for the discovery of target-specific new drugs. The six potential sclerostin inhibitors suppressed the level of both intracellular and/or extracellular sclerostin in mouse osteocyte IDG-SW3 and increased alkaline phosphatase activity in IDG-SW3 cells, human bone marrow-derived mesenchymal stem cells and human fetal osteoblasts hFOB1.19. Potential small-molecule drug candidates obtained in this study are expected to provide new therapeutics for osteoporosis as well as insights into the structure-activity relationship of sclerostin inhibitors for rational drug design.

An innovative nonpharmacological intervention combined with intravenous patient-controlled analgesia increased patient global improvement in pain and satisfaction after major surgery.

PURPOSE: This study aimed to evaluate whether a nonpharmacological approach through implementation of a communication improvement program (named CICARE for Connect, Introduce, Communicate, Ask, Respond and Exit) into standard operating procedure (SOP) in acute pain service (APS) improved satisfaction in patients receiving intravenous patient-controlled analgesia (IV-PCA). PATIENTS AND METHODS: This was a nonrandomized before-after study. Adult patients (aged between 20 and 80 years) who received IV-PCA after major surgery were included. Implementing CICARE into SOP was conducted in APS. Anonymous questionnaires were used to measure outcomes in this prospective two-part survey. The first part completed by APS nurses contained patients' characteristics, morphine dosage, delivery/demand ratios, IV-PCA side effects and pain at rest measured with an 11-point numeric rating scale (NRS, 0-10). A score of NRS ≥4 was defined as inadequately treated pain. The ten-question second part was completed by patients voluntarily after IV-PCA was discontinued. Each question was assessed with a 5-point Likert scale (1: extremely poor; 5: excellent). Patients were separated into "before" and "after" CICARE groups. Primary outcomes were patient global impression of improvement in pain (PGI-Improvement) and patient satisfaction. Secondary outcomes included quality of communication skills, instrument proficiency and accessibility/availability of IV-PCA. RESULTS: The response rate was 55.3%, with 187 usable questionnaires. CICARE effectively improved patient global impression of improvement in pain, patient satisfaction, communication skills and accessibility/availability of IV-PCA. No significant differences were noted in instrument proficiency, morphine dosage, delivery/demand ratios, rates of inadequately treated pain at rest and side effects of IV-PCA between groups. Paradoxical findings were noted between the rates of inadequately treated pain/side effects and PGI-Improvement in pain/patient satisfaction, which were affected by psychological factors. CONCLUSION: Nonpharmacological interventions carried out by implementing CICARE into SOP for APS effectively improved patient satisfaction and postoperative pain management quality, but this did not affect actual pain.

Successful removal of a potentially lethal left atrial thrombus detected by transesophageal echocardiography following the removal of a left ventricular assist device inflow cannula.

The left ventricular assist device (LVAD) is a battery-operated, mechanical pump-type device that helps in maintaining the pumping ability of a failing heart. Thromboembolism poses a significant risk during and after LVAD implantation. It occurs in up to 35% of patients with adverse sequelae. We present the case of a 75-year-old man who underwent coronary artery bypass graft surgery and LVAD implantation for acute myocardial ischemia and severe left ventricular dysfunction. However, subsequent transthoracic echocardiographic examination revealed an LVAD thrombus, and LVAD removal was suggested following the failure of thrombolytic therapy. After the LVAD cannula was removed, transesophageal echocardiography (TEE) revealed a residual thrombus in the left atrium. Thrombectomy was successfully performed by opening the left atrium with cardiopulmonary bypass. We believe that TEE monitoring aided the implantation and removal of the LVAD device. In this case, we found that TEE not only helped in monitoring the ventricular function but also in detecting other problems such as the residual thrombus. We strongly recommend TEE monitoring during the entire LVAD-removal procedure, particularly for patients who need to undergo LVAD removal because of thrombosis formation.

Successful management of contrast medium extravasation injury through stellate ganglion block and intra-arterial nitroglycerin.

We describe the successful management of extravasation injury to the left hand by contrast medium with stellate ganglion block and intra-arterial nitroglycerin in a patient which befell during contrast-enhanced imaging. The incidence of contrast-medium extravasation injury is increasing because of the convenience and availability of contrast-enhanced imaging and ease of injection access. Extravasation of contrast medium may results in severe pain, erythema, cyanosis, and edema or even skin necrosis, which is largely related to the ionization, osmolarity, and volume of the contrast medium. The conservative treatment is often adequate in small amount extravasation, but if the extravasation is overwhelming further energetic management is mandatory. A 29-year-old man was brought to our emergency because of diffuse abdominal pain and he was arranged to receive intravenous contrast media enhanced abdominal computed tomography for diagnosis. Ruptured appendicitis with abscess formation was suspected; then the patient underwent emergent appendectomy and drainage of the abscess. However, severe swelling and cyanotic change that radiated from the intravenous catheter insertion site in every direction over the entire dorsum of the left hand were noted after the surgery. Contrast-medium extravasation injury was highly contemplated and a left stellate ganglion block was performed immediately for relief of symptoms. The consulting surgeon ruled out compartment syndrome, but advised emergent left upper limb arteriography, which revealed signs of vasospasm with high intravascular pressure of the left distal ulnar and radial arteries; thus nitroglycerin was injected into left distal ulnar and radial arteries for relief of vasospasm. The clinical symptoms were improved after the above managements and the patient was discharged 7 days later without any sequela.