Single Dose of Sodium Zirconium Cyclosilicate Versus Sodium Polystyrene Sulfonate in Hospitalized Patients With Hyperkalemia.

BACKGROUND: Sodium zirconium cyclosilicate (SZC) is an inorganic zirconium silicate compound that selectively exchanges potassium for hydrogen and sodium. "Once" doses of SZC (with option to redose) in patients with hyperkalemia in hospitalized settings have not been evaluated. We hypothesized that a once dose of SZC would be non-inferior to sodium polystyrene sulfonate (SPS) in reducing serum potassium. OBJECTIVE: The objective of our study is to evaluate the effect of a "once" dose of SZC when compared with SPS in reducing serum potassium levels. METHODS: This was a retrospective analysis of patients who received either a "once" dose of SZC or single or repeated doses of SPS for hyperkalemia. The primary endpoint was mean absolute reduction in the first serum potassium value at least 4 hours after administration. The secondary efficacy endpoints were the rate of additional potassium-lowering therapies and the rate of normokalemia within 48 hours. Safety endpoints were the incidence of electrolyte abnormalities, hypoglycemia, hypertension, hypotension, and colonic necrosis. RESULTS: A total of 260 patients were included in the analysis. The mean initial serum potassium was similar between groups (5.6 ± 0.4). The absolute serum potassium reduction was -0.88 ± 0.64 mEq/L and -0.75 ± 0.65 mEq/L with SZC and SPS, respectively. The "once" regimen of SZC demonstrated non-inferiority compared with SPS (P < 0.0001). The proportion of patients achieving normokalemia within 48 hours and the proportion of patients receiving additional potassium-lowering therapies did not differ between groups. CONCLUSION AND RELEVANCE: The "once" dose regimen (with redose option) of SZC was non-inferior to the "once" or repeated dosing regimen of SPS with regard to absolute potassium reduction. There were no significant differences in the rate of additional potassium-lowering therapies and the rate of normokalemia at 48 hours. The incidence of hypertension was less common among patients who received SZC.

Korean red ginseng saponin fraction rich in ginsenoside-Rb1, Rc and Rb2 attenuates the severity of mouse collagen-induced arthritis.

Despite a multitude of reports on anti-inflammatory properties of ginseng extracts or individual ginsenosides, data on antiarthritic effect of ginseng saponin preparation with mixed ginsenosides is limited. On the other hand, a combined therapy of safe and inexpensive plant-derived natural products such as ginsenosides can be considered as an alternative to treat arthritis. Our previous in vitro data displayed a strong anti-inflammatory action of red ginseng saponin fraction-A (RGSF-A). We, herein, report a marked antiarthritic property of RGSF-A rich in ginsenoside Rb1, Rc, and Rb2. Collagen-induced arthritic (CIA) mice were treated with RGSF-A or methotrexate (MTX) for 5 weeks. Joint pathology, serum antibody production and leukocye activation, cytokine production in the circulation, lymph nodes, and joints were examined. RGSF-A markedly reduced severity of arthritis, cellular infiltration, and cartilage damage. It suppressed CD3(+)/CD69(+), CD4(+)/CD25(+), CD8(+) T-cell, CD19(+), B220/CD23(+) B-cell, MHCII(+)/CD11c(+), and Gr-1(+)/CD11b(+) cell activations. It further suppressed anti-CII- or anti-RF-IgG/IgM, TNF-α, IL-1ß, IL-17, and IL-6 secretions but stimulated IL-10 levels in the serum, joint, or splenocyte. RGSF-A attenuated arthritis severity, modified leukocyte activations, and restored cytokine imbalances, suggesting that it can be considered as an antiarthritic agent with the capacity to ameliorate the immune and inflammatory responses in CIA mice.

Safety and Feasibility of Opening Tamsulosin Capsules for Enteral Feeding Tube Administration.

Purpose: Tamsulosin is formulated as sustained release beads within a capsule to prevent rapid absorption and associated hypotension. The package insert advises the capsule is swallowed whole; not crushed, chewed, or opened. To our knowledge, there are no current data on opening capsules for adults with enteral tube feeds. Given the unidentified safety and efficacy of administration via enteral tubes, alternative alpha blockers with less selectivity for alpha1A are often used. Methods: A single center retrospective chart review was conducted at two hospital sites. Adult patients that received at least one dose of tamsulosin or doxazosin while an enteral feeding tube was placed were included. Safety outcomes evaluated were the number of documented tube obstructions and incidence of medication associated hypotension. Results: 169 patients were included. Ten enteral feeding tube obstructions were reported, 4 of 110 (3.64%) in the tamsulosin arm and 6 of 59 (10.17%) in the doxazosin arm (RR .36, 95% CI .11 to 1.22, P = .099). At least 1 episode of medication associated hypotension occurred in 22 of 98 (22.45%) in the tamsulosin arm and 20 of 49 (40.82%) in the doxazosin arm (RR .55, 95% CI .33 to .91, P = .019). Conclusion: There was no statistically significant difference in the number of tube obstructions between patients receiving tamsulosin or doxazosin via enteral tube feeds. Patients receiving doxazosin were at increased risk of experiencing medication related hypotension. Tamsulosin capsules may be opened and administered via enteral feeding tubes if administered with content integrity intact.

Long-term Anticoagulation with Apixaban in Patients with Cerebral Venous Thrombosis.

Introduction: Cerebral venous thrombosis (CVT) is a life-threatening neurological condition. There is limited evidence for the use of direct oral anticoagulants (DOAC) for long-term anticoagulation in this patient population. We report a case series of patients treated with apixaban and their clinical course. Methods: This was a retrospective cohort study. Patients diagnosed with CVT in a defined time period at our institution were screened for long-term anticoagulation and patients who were treated with apixaban were included in this study. Results: A total of nine patients were included in this study. The mean age was 36 years and 56% of the patients included were women. All received initial anticoagulation with unfractionated heparin (UFH) infusion for at least twenty-four hours, except for one patient who had anti-thrombin III deficiency and was treated with argatroban infusion. For long-term anticoagulation, 56% of patients received apixaban 10 mg twice daily for the first five to seven days followed by 5 mg twice daily, while the remaining 44% were transitioned from IV anticoagulation to apixaban 5 mg twice daily. There were no adverse events reported, except for one patient who developed anemia after 7 months of treatment and required a blood transfusion. Complete recanalization was achieved in 78% while 22% had partial recanalization. Follow-up time ranged from six to twenty-three months. Conclusion: The use of apixaban for long-term anticoagulation in CVT resulted in recanalization in all of the patients in this case series without any major side effects. This case series adds to the emerging studies demonstrating the utility of apixaban for CVT.

Lipid metabolic effect of Korean red ginseng extract in mice fed on a high-fat diet.

BACKGROUND: Ginseng saponin and ginsenosides exert anti-obesity effects via the modulation of physiological lipid metabolism in vivo or intracellular signalling in cell culture systems. However, the complicated relationship between the anti-obesity effects of ginseng and gene expression has yet to be defined under in vivo conditions. Therefore, we evaluated the relationship between the anti-obesity effects of Korean red ginseng extract (KRGE) and hepatic gene expression profiles in mice fed long-term on a high-fat diet (HFD) in this study. RESULTS: KRGE reduces the levels of cholesterol, low-density lipoprotein-cholesterol (LDL-C), serum triglycerides, and atherogenic indices. Levels of leptin, adiponectin and insulin, which regulate glucose and lipid metabolism, were impaired profoundly by HFD. However, KRGE treatment brought these levels back to normal. KRGE was found to down-regulate genes associated with lipid metabolism or cholesterol metabolism (Lipa, Cyp7a1, Il1rn, Acot2, Mogat1, Osbpl3, Asah3l, Insig1, Anxa2, Vldlr, Hmgcs1, Sytl4, Plscr4, Pla2g4e, Slc27a3, Enpp6), all of which were up-regulated by HFD. CONCLUSION: KRGE regulated the expression of genes associated with abnormal physiology via HFD. Leptin, insulin, and adiponectin, which carry out critical functions in energy and lipid metabolism, were shown to be modulated by KRGE. These results show that KRGE is effective in preventing obesity.

Systemic and Local Anaphylaxis is Not Induced by Korean Red Ginseng Mixture in Guinea Pigs.

Currently, injuries to customers due to health functional foods are annually increasing. To evaluate the antigenicity of Korean red ginseng mixture (KRGM), we tested for systemic anaphylactic shock and passive cutaneous anaphylaxis in guinea pigs. Based on a comparison of measured body weights, there were no changes in body weight for the KRGM treatment group compared with the control group. In the ovalbumin treated group, however, there was a statistically significant decrease in body weight. For the active systemic anaphylaxis test, after the induction, there were no symptoms that suggested anaphylactic shock in the control and KRGM treatment group. In the ovalbumin treated group, there were symptoms that suggested severe anaphylaxis, and those symptoms included restlessness, piloerection, tremor, rubbing or licking the nose, sneezing, coughing, hyperpnea, dyspnea, staggering gait, jumping, gasping and writhing, convulsion, side position and Cheyne-stokes respiration. All animals died within thirty minutes in the ovalbumin treated group. For the passive cutaneous anaphylaxis test in guinea pigs sensitized to KRGM, each anti-serum was diluted in a stepwise manner. This was followed by an intravenous injection of a mixture of KRGM and Evans blue. The results of the test showed that all the responses were negative in the control and the low-dose and high-dose administration groups. However, in the ovalbumin treated group, all the responses were positive. Based on the above results, there were no anaphylactic responses for up to 12 times the amount of human intake of KRGM in Hartley Guinea-pigs. The results suggest that KRGM is safe as measured by the systemic and local antigenicity in guinea pigs.

Korean Red Ginseng Saponin Fraction Downregulates Proinflammatory Mediators in LPS Stimulated RAW264.7 Cells and Protects Mice against Endotoxic Shock.

Korean red ginseng has shown therapeutic effects for a number of disease conditions. However, little is known about the antiinflammatory effect of Korean red ginseng saponin fraction (RGSF) in vitro and in vivo. Therefore, in this study, we showed that RGSF containing 20(S)-protopanaxadiol type saponins inhibited nitric oxide production and attenuated the release of tumor necrotic factor (TNF)-α, interleukin (IL)-6, granulocyte monocyte colony stimulating factor (GMCSF), and macrophage chemo-attractant protein-1 in lipopolysaccharide (LPS) stimulated murine macrophage RAW264.7 cells. Moreover, RGSF down-regulated the mRNA expressions of inducible nitric oxide synthase, cyclooxyginase-2, IL-1ß, TNF-α, GMCSF, and IL-6. Furthermore, RGSF reduced the level of TNF-α in the serum and protected mice against LPS mediated endotoxic shock. In conclusion, these results indicated that ginsenosides from RGSF and their metabolites could be potential sources of therapeutic agents against inflammation.

Red ginseng saponin fraction a isolated from korean red ginseng by ultrafiltration on the porcine coronary artery.

Red ginseng saponin fraction-A (RGSF-A) contains a high percentage of panaxadiol saponins that were isolated from Korean red ginseng by ultrafiltration. The aim of this study was to elucidate the effects of RGSF-A on the porcine distal left anterior descending (LAD) coronary artery. The relaxant responses to RGSF-A were examined during contractions induced by 100 nM U46619 (9,11-dideoxy-9a,11a-methanoepoxy-prostaglandin F2a), a stable analogue of thromboxane A2. RGSF-A dose-dependently induced biphasic (fast- and slow-) relaxation in the distal LAD coronary artery in the presence of an intact endothelium. The fast-relaxation was quickly achieved in a minute, and then the slow-relaxation was slowly developed and sustained for more than thirty minutes after the administration of RGSF-A. The slow-relaxation had a tendency to be bigger than the fast-relaxation. Fast relaxation induced by RGSF-A was almost blocked by N ω-Nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a guanylate cyclase inhibitor. However slow-relaxation induced by RGSF-A was only partially inhibited by L-NAME and ODQ. In the endothelium-removed ring, RGSF-A evoked only slow-relaxation to a certain extent. These data suggest that RGSF-A induced both endothelium dependent fast- and slow-relaxation and endothelium independent slow-relaxation in the porcine distal LAD coronary artery. The endothelium dependent fast-relaxation is mediated by the nitric oxide (NO)-cGMP pathway, and the endothelium dependent slow-relaxation is at least partially mediated by the NO-cGMP pathway. However, the endothelium-independent slow-relaxation remains to be elucidated.

Enhancement of antitumor effects of paclitaxel (taxol) in combination with red ginseng acidic polysaccharide (RGAP).

We have recently reported that red ginseng acidic polysaccharide (RGAP), isolated from Korean red ginseng (Panax ginseng C.A. Meyer), shows immunomodulatory and antitumor activities, mainly mediated by the nitric oxide (NO) production of macrophages. This compound may be used in cancer therapy alone or in combination with other chemotherapeutic agents. The synergistic effect of RGAP and paclitaxel (taxol) was evaluated to develop new biological response modifiers in cancer therapy. The present study demonstrates a synergistic antitumor effect of RGAP and paclitaxel in mice transplanted with sarcoma 180 and B16 melanoma. Combined treatment with paclitaxel (5 or 15 mg/kg) and RGAP (25 mg/kg) resulted in a 28.6 or 42.8 % increase in the life span of ICR mice bearing sarcoma 180 tumor cells, while no obvious effect was seen on sole paclitaxel treatment. When a combination of paclitaxel (10 mg/kg) and RGAP (100 mg/kg) was administered to C57BL/6 mice implanted with B16 melanoma, the tumor weight per mouse also decreased by 76.3 %, suggesting that RGAP may be used as an adjuvant in medicinal applications of paclitaxel. The augmented antitumor effect of paclitaxel is supposed to be the result of the immunomodulating antitumor effect of RGAP. RGAP, having B cell specific mitogenic activity, induced the secretion of interleukin-6 (IL-6) in spleen cells in a concentration-dependent manner (5 to 500 microg/microL). RGAP also restored the proliferation of splenocytes and NK cell activity suppressed by paclitaxel. Flow cytometric analysis of splenocytes in mice treated with paclitaxel showed a significant increase of CD11b+ cells. Additionally, a synergistic effect of RGAP and paclitaxel was found to effect an increased tumoricidal activity of macrophages. The above results suggest that clinical trials of RGAP as an adjuvant in cancer chemotherapy of paclitaxel are highly feasible.