Plasmapheresis in the treatment of multi-drug intoxication involving levothyroxine sodium and calcium channel blockers: a case report.

Plasmapheresis, a procedure used to remove large molecular weight, protein-bound molecules from a patient's blood, has been shown to be useful in some cases of drug overdose. Levothyroxine sodium intoxication may result from the intentional or accidental ingestion of excessive amounts of the hormone, which can trigger a thyroid storm. However, case reports about the extremely large dose of 15,000 µg of thyroxine intoxication are extremely rare, and even combined with calcium channel blockers (CCBs) poisonings. We present a case of an intentional poisoning with high doses of thyroxine, diltiazem and amlodipine successfully treated with plasma exchange. A 40-year-old woman was admitted showing unconsciousness and sustained hypotension with high levels of thyroid hormones (THs). It was discovered that she had secretly ingested at least 15,000 µg of levothyroxine sodium and CCBs with unknown amounts of diltiazem and amlodipine. Following plasmapheresis, the levels of TH declined dramatically after each of the 4 sessions, with hemodynamics gradually stabilizing and mental state improving. The early and timely use of plasmapheresis appears to be a vital therapeutic tool for the management of acute and severe forms of l-thyroxine and CCB intoxication. Its use can prevent thyroid storm and reverse the disturbances in the patient's hemodynamic status.

Curcumin-Loaded TPGS/F127/P123 Mixed Polymeric Micelles for Cervical Cancer Therapy: Formulation, Characterization, and InVitro and InVivo Evaluation.

Cervical cancer is the fourth most common cancer in women worldwide, and existing treatments cause severe side effects and great burdens. Thus, the development of safe, inexpensive therapeutic agents is necessary. Curcumin (Cur), a well-known natural product, exerts promising anti-cancer activities against various cancer types. However, its therapeutic efficacy is severely restrained due to rapid degradation, poor aqueous solubility, and low bioavailability. The objective of this study was to investigate the therapeutic potential of novel curcumin-loaded TPGS/F127/P123 mixed polymeric micelles (Cur@NPT100) for cervical cancer treatment. The Cur@NPT100 exhibited an average size of approximately 19 nm, a zeta potential of around -4 mV, a drug loading of 8.18 ± 0.36%, and an encapsulation efficiency of 79.38 ± 4.65%. Unlike free Cur, Cur@NPT100 are readily dispersed in aqueous medium, showing enhanced stability and a sustained release profile over a 6-day period. In vitro cell culture experiments revealed that TPGS/F127/P123 mixed polymeric micelles (NPT100) based nanocarriers substantially promoted the selective cellular uptake of Cur into HeLa cells rather than by non-cancerous NIH3T3 cells, inducing higher cytotoxicity and greater apoptosis and significantly increasing the percentage of cells arrested at the G2/M phase of the cell cycle. Additionally, the Cur@NPT100 facilitated more Cur accumulation in the mitochondria and decreased the mitochondrial membrane potential. In addition, western blot assays demonstrated that Cur@NPT100 were more potent than free Cur at activating the mitochondria-mediated apoptosis pathway. In vivo results further confirmed that Cur@NPT100 exhibited a much higher antitumor efficacy than free Cur and had excellent biocompatibility. In conclusion, Cur@NPT100 might be an effective therapeutic agent for cervical cancer.

Discovery of Xuebijing Injection Exhibiting Protective Efficacy on Sepsis by Inhibiting the Expression of HMGB1 in Septic Rat Model Designed by Cecal Ligation and Puncture.

Xuebijing (XBJ) injection is a complex traditional Chinese prescription that has been widely used to treat sepsis in China. However, its underlying mechanisms on sepsis still remain uninvestigated. In this study, 150 male Sprague Dawley rats were randomly divided into a normal control group, cecal ligation and puncture (CLP) group, CLP+XBJ group, and CLP+gibberellic acid group. Each of them contained 3 subgroups of different treatment periods (12, 24, and 48 hours after injection, respectively). The mRNA expression of HMGB1 in liver tissue of the 4 groups was calculated by the semiquantitative reverse-transcription polymerase chain reaction. The level of IL-6, IL-10, and TNF-α was determined by an enzyme-linked immunosorbent assay. Immunohistochemical analysis for HMGB1 showed the effect of XBJ on infiltration of inflammatory cells. The mRNA expression of HMGB1 in liver tissue in CLP+XBJ and CLP+gibberellic acid groups was lower than that in the CLP group. The levels of IL-6, IL-10, and TNF-α were decreased at the each monitored time point. All these results indicated that XBJ exhibits protective efficacy on sepsis by inhibiting the expression of HMGB1.

Refractoriness of the sheep superior vena cava myocardial sleeve.

The cardiomyocytes in the superior vena cava (SVC) myocardial sleeve have distinct action potentials and ionic current profiles, but the refractoriness of these cells has not been reported. Using standard intracellular microelectrode techniques, we demonstrated in sheep that the effective refractory period (ERP) of the cardiomyocytes in the SVC (114.7 +/- 6.5 ms) is shorter than that in the inferior vena cava (IVC) (166.7 +/- 6.2 ms), right atrial free wall (RAFW) (201.0 +/- 6.0 ms) and right atrial appendage (RAA) (203.1 +/- 5.8 ms) (P < 0.05). The right atrial cardiomyocyte ERP was heterogeneously shortened by acetylcholine, a muscarinic type 2 receptor (M(2)R) agonist. After perfusion with 15 microM acetylcholine, the shortest ERP occurred in the SVC (the ERP in the SVC, IVC, RAFW and RAA was 53.6 +/- 2.7, 98.9 +/- 2.2, 121.8 +/- 6.0 and 109.7 +/- 5.1 ms, respectively; P < 0.05). Carbachol (1 microM), another M(2)R agonist, produced a similar effect as acetylcholine. Furthermore, we used methoctramine, a M(2)R blocker, 4-DAMP, a muscarinic type 3 receptor (M(3)R) blocker, and tropicamide, a muscarinic type 4 receptor (M(4)R) blocker to inhibit the acetylcholine-induced ERP shortening of SVC cardiomyocytes, and found that the 50% inhibitory concentration for methoctramine, 4-DAMP and tropicamide was 5.91, 45.72 and 80.34 nM, respectively. Therefore, we conclude that the sheep SVC myocardial sleeve is a unique electrophysiological region of the right atrium with the shortest ERP both under physiological condition and under cholinergic agonist stimulation. M(2)R might play a major role in the response of the SVC myocardial sleeve to parasympathetic nerve tone. The association between the distinct refractoriness in SVC and atrial fibrillation originating from the region deserves further investigation.