Analysis of Self-Assembled Low- and High-Molecular-Weight Poly-L-Lysine-Ce6 Conjugate-Based Nanoparticles.

In cancer therapy, photodynamic therapy (PDT) has attracted significant attention due to its high potential for tumor-selective treatment. However, PDT agents often exhibit poor physicochemical properties, including solubility, necessitating the development of nanoformulations. In this study, we developed two cationic peptide-based self-assembled nanomaterials by using a PDT agent, chlorin e6 (Ce6). To manufacture biocompatible nanoparticles based on peptides, we used the cationic poly-L-lysine peptide, which is rich in primary amines. We prepared low- and high-molecular-weight poly-L-lysine, and then evaluated the formation and performance of nanoparticles after chemical conjugation with Ce6. The results showed that both molecules formed self-assembled nanoparticles by themselves in saline. Interestingly, the high-molecular-weight poly-L-lysine and Ce6 conjugates (HPLCe6) exhibited better self-assembly and PDT performance than low-molecular-weight poly-L-lysine and Ce6 conjugates (LPLCe6). Moreover, the HPLCe6 conjugates showed superior cellular uptake and exhibited stronger cytotoxicity in cell toxicity experiments. Therefore, it is functionally beneficial to use high-molecular-weight poly-L-lysine in the manufacturing of poly-L-lysine-based self-assembling biocompatible PDT nanoconjugates.

Design and development of novel self-assembled catechol-modified bile acid conjugates as pH-responsive apical sodium-dependent bile acid transporter targeting nanoparticles.

Catechol-based biomaterials demonstrate biocompatibility, making them suitable for a wide range of therapeutic applications when integrated into various molecular frameworks. However, the development of orally available catechol-based biomaterials has been hindered by significant pH variations and complex interactions in the gastrointestinal (GI) tract. In this study, we introduce a novel catechol-modified bile acid (CMBA), which is synthesized by anchoring the FDA-approved drug, ursodeoxycholic acid to the neurotransmitter dopamine. This modification could form a new apical sodium-dependent bile acid transporter (ASBT) inhibitor (ASBTi) due to the bile acid moiety. The computational analysis using the TRAnsient Pockets in Proteins (TRAPP) module, coupled with MD simulations, revealed that CMBA exhibits a strong binding affinity at residues 51-55 of ASBT with a low inhibitory constant (Ki) value. Notably, in slightly alkaline biological conditions, CMBA molecules self-assemble into carrier-free nanoparticles with an average size of 240.2 ± 44.2 nm, while maintaining their ability to bind with ASBT. When administered orally, CMBA accumulates in the ileum and liver over 24 h, exhibiting significant therapeutic effects on bile acid (BA) metabolism in a high-fat diet (HFD)-fed mouse model. This study underscores the therapeutic potential of the newly developed catechol-based, pH-responsive ASBT-inhibiting nanoparticles presenting a promising avenue for advancing therapy.

Evaluation of medication dosing errors in elderly patients with renal impairment
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OBJECTIVE: The administration of the usual dosage of medication in elderly patients with renal impairment can cause adverse drug reactions due to patients' decreased renal function. Using retrospective prescription analysis, in a teaching hospital, this study aimed to evaluate medication dosing errors in elderly patients with renal impairment and the risk factors for these dosing errors. MATERIALS AND METHODS: This retrospective study included elderly patients with a creatinine clearance of 59 mL/min or less who were hospitalized in a teaching hospital between July 1, 2015, and September 30, 2015. Data including the patients' age, gender, weight, serum creatinine, duration of hospital stay, and discharge prescriptions were obtained from electronic medical records. Patients with dosing errors were identified, and the risk factors for the dosing errors were statistically analyzed. RESULTS: Out of 497 patients, 164 (33%) had evidence of dosing errors. All metformin prescriptions (n = 38) were associated with dosing errors (100%), and trimetazidine was prescribed 11 times in cases where it was contraindicated (31%). The following were confirmed to be statistically significant risk factors that increased the likelihood of the dosing errors: the patient's age (odds ratio (OR): 1.050, 95% confidence interval (CI): 1.011 - 1.092), the number of drugs prescribed per patient (OR: 1.106; 95% CI: 1.012 - 1.210), and the number of drugs requiring dosing adjustments in patients with renal impairment (OR: 1.996; 95% CI: 1.614 - 2.468). CONCLUSION: There was a considerable rate of dosing errors in hospitalized elderly patients with renal impairment. It is necessary for healthcare professionals to make appropriate dosage adjustments in elderly patients with renal impairment to improve the outcomes of pharmacotherapy and patients' quality of life.
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Effects of vitamin D on blood pressure in patients with type 2 diabetes mellitus.

PURPOSE: Previous studies have suggested that vitamin D supplementation may decrease blood pressure in patients with type 2 diabetes, although conflicting results have been reported. The purpose of this meta-analysis was to evaluate the effects of the vitamin D supplementation on blood pressure in patients with type 2 diabetes. METHODS: A meta-analysis of published randomized controlled trials was conducted. Eligible studies were identified via a literature search of the MEDLINE (PubMed), EMBASE, and Cochrane Library databases through to May 25, 2015. The endpoint of the analysis was the change in blood pressure due to vitamin D treatment in patients with type 2 diabetes. These changes were calculated as the difference between the baseline and final measurements performed in each study. A fixed-effects model was used to calculate the combined effect estimates; in the presence of heterogeneity, a random-effects model was used. RESULTS: A total of 15 articles were included in the meta-analysis. All 15 articles, including 1,134 patients with type 2 diabetes, were analyzed for systolic blood pressure (SBP), and 13 articles, including 793 patients, were analyzed for diastolic blood pressure (DBP). The combined-effect estimate of vitamin D intervention on SBP was -0.121 mmHg (95% confidence interval (CI) -0.355 to 0.113, p = 0.311), and considerable heterogeneity was observed between studies (p < 0.001, I(2)= 74.2%). For DBP, the combined effect estimate was -0.160 mmHg (95% CI -0.298 to -0.022, p = 0.023), and no heterigenieity was observed (p = 0.673, I(2) = 0.0%). CONCLUSIONS: This study is the first meta-analysis of the effect of vitamin D supplementation on blood pressure in patients with type 2 diabetes. This meta-analysis demonstrated that vitamin D supplementation may result in a reduction in DBP in patients with type 2 diabetes. However, additional studies with large sample sizes and longer durations are needed to establish a relationship between vitamin D and blood pressure in patients with type 2 diabetes.

A case of Echinostoma cinetorchis (Trematoda: Echinostomatidae) infection diagnosed by colonoscopy.

Human cases of echinostomiasis have been sporadically diagnosed by extracting worms in the endoscopy in Korea and Japan. Most of these were caused by Echinostoma hortense infection. However, in the present study, we detected 2 live worms of Echinostoma cinetorchis in the ascending colon of a Korean man (68-year old) admitted to the Gyeongsang National University Hospital with complaint of intermittent right lower quadrant abdominal pain for 5 days. Under colonoscopy, 1 worm was found attached on the edematous and hyperemic mucosal surface of the proximal ascending colon and the other was detected on the mid-ascending colon. Both worms were removed from the mucosal surface with a grasping forceps, and morphologically identified as E. cinetorchis by the characteristic head crown with total 37 collar spines including 5 end-group ones on both sides, disappearance of testes, and eggs of 108×60 µm with abopercular wrinkles. The infection source of this case seems to be the raw frogs eaten 2 months ago. This is the first case of endoscopy-diagnosed E. cinetorchis infection in Korea.

Clinical significance of the presence of autonomic and vestibular dysfunction in diabetic patients with peripheral neuropathy.

BACKGROUND: We investigated the prevalence of diabetic autonomic neuropathy (DAN) and vestibular dysfunction (VD) in diabetic patients with peripheral neuropathy. METHODS: Thirty-five diabetic patients with peripheral neuropathy were enrolled from August 2008 to July 2009. All subjects underwent autonomic function tests. Nineteen of the patients (54.3%) underwent videonystagmography. RESULTS: Diabetic autonomic neuropathy was observed in 28 patients (80%). A mild degree of autonomic failure was observed in 18 patients (64.3%), and a moderate degree of autonomic failure was observed in ten patients (35.7%). Factors related to DAN included diabetic nephropathy (P=0.032), degree of chronic kidney disease (P=0.003), and duration of diabetes (P=0.044). Vestibular dysfunction was observed in 11 of 19 patients (57.9%). There was no significant association between DAN and VD. CONCLUSION: Diabetic autonomic neuropathy was observed in 28 diabetic patients (80%) with peripheral neuropathy. Vestibular dysfunction was observed in nearly 60% of diabetic patients with peripheral neuropathy who complained of dizziness but showed no significant association with DAN. Diabetic patients who complained of dizziness need to examine both autonomic function and vestibular function.

Thyrotoxicosis with coronary spasm that required coronary artery bypass surgery.

We describe a 47-year-old woman with severe coronary vasospasm induced by hyperthyroidism. The patient complained of anginal chest pain without specific characteristics of thyrotoxicosis. Coronary arteriography was performed and revealed 90% stenosis of both the left and right coronary os. She was treated with emergent coronary artery bypass graft surgery. Postoperatively, she exhibited a comatose mentality. Severe thyrotoxicosis was indicated on thyroid function tests and thyrotoxic storm was diagnosed. Nineteen days after the surgery and following the initiation of propylthiouracil treatment, coronary arteriography revealed entirely normal coronary arteries.