Anti-inflammatory Test of Centella Asiatica Extract on Rat Induced by Cadmium

Cadmium is a toxic heavy metal. The present of cadmium caused inflammation in liver. This study aims to know the anti inflammatory of Centella asiatica extract on rat induced by cadmium. This research was an experimental study using post test only control group design. Twenty four rats divided into six groups with four replications, i.e group of healthy control (C1), negative control induced by CdSO4 with dosage 56 mg/kg for 14 days and treatment (C3-C6) with dosage of 100, 200 ,300 and 400 mg/kg of C. asiatica. The blood Cd, GST, GSH, TNF- α and COx2 were measured after a 21 days administration of C. asiatica. The data were analyzed by ANOVA test followed by Duncan test with a significance level of 5%. The result showed that administrating C.asiatica can neutralized cadmium, improve inflammation in liver.The conclusion of our research that C.asiatica extract can decrease Cd level, TNF-α and COx2 levels and increase GST and GSH level in rat induced by cadmium. A 200 mg/kg was the effective dosage to reduce Cd, TNF-α and COx2 levels and increase GST and GSH levels. Key words : anti inflammatory, Cd, Centella asiatica, GST, COX2

The Influence of Wuzhi Capsule on the Pharmacokinetics of Cyclophosphamide

Background: Cyclophosphamide is approved for the treatment of a variety of tumors, yet the use of cyclophosphamide is limited by kidney and liver toxicity. In the clinic, the Wuzhi capsule is approved to attenuate cyclophosphamide toxicity in the kidney and liver. Objective: We aimed to investigate the effects of the principal ingredients of Wuzhi capsule, schisandrin A (SIA) and schisantherin A (STA), on the pharmacokinetics of cyclophosphamide. Methods: The essential pharmacokinetic data and physicochemical parameters of SIA, STA, and cyclophosphamide were collected. Physiologically based pharmacokinetic (PBPK) models of SIA, STA, and cyclophosphamide were built in Simcyp Simulator and verified using published clinical pharmacokinetic data. The verified PBPK models were used to predict potential herb-drug interactions (HDIs) between cyclophosphamide and SIA and STA in cancer patients. Results: The area under the plasma concentration–time curve (AUC) of cyclophosphamide was increased by 18% and 1% when co-administered with STA and SIA at a single dose, respectively, and increased by 301% and 29% when co-administered with STA and SIA at multiple doses, respectively. The maximum concentration (Cmax) of cyclophosphamide was increased by 75% and 7% when co-administered with STA and SIA at multiple doses, respectively. Conclusion: The AUC and Cmax of cyclophosphamide were increased when cyclophosphamide was combined with the Wuzhi capsule, compared to cyclophosphamide alone. Our study shows that the adverse drug reactions and toxicity of cyclophosphamide should be closely monitored and an effective dosage adjustment of cyclophosphamide may need to be considered when co-administered with the Wuzhi capsule.

Shenjinhuoxue Mixture Attenuates Inflammation, Pain, and Cartilage Degeneration by Inhibiting TLR-4 and NF-κB Activation in Rats with Osteoarthritis: A Synergistic Combination of Multitarget Active Phytochemicals

Osteoarthritis (OA), a highly prevalent chronic joint disease, involves a complex network of inflammatory mediators that not only triggers pain and cartilage degeneration but also accelerates disease progression. Traditional Chinese medicinal shenjinhuoxue mixture (SHM) shows anti-inflammatory and analgesic effects against OA with remarkable clinical efficacy. This study explored the mechanism underlying anti-OA properties of SHM and evaluated its efficacy and safety via in vivo experiments. Through network pharmacology and published literature, we identified the key active phytochemicals in SHM, including β-sitosterol, oleanolic acid, licochalcone A, quercetin, isorhamnetin, kaempferol, morusin, lupeol, and pinocembrin; the pivotal targets of which are TLR-4 and NF-κB, eliciting anti-OA activity. These phytochemicals can enter the active pockets of TLR-4 and NF-κB with docking score ≤ − 3.86 kcal / mol , as shown in molecular docking models. By using surface plasmon resonance assay, licochalcone A and oleanolic acid were found to have good TLR-4-binding affinity. In OA rats, oral SHM at mid and high doses (8.72 g/kg and 26.2 g/kg) over 6 weeks significantly alleviated mechanical and thermal hyperalgesia ( P < 0.0001 ). Accordingly, the expression of inflammatory mediators (TLR-4, interleukin (IL-) 1 receptor-associated kinase 1 (IRAK1), NF-κB-p65, tumor necrosis factor (TNF-) α, IL-6, and IL-1β), receptor activator of the NF-κB ligand (RANKL), and transient receptor potential vanilloid 1 (TRPV1) in the synovial and cartilage tissue of OA rats was significantly decreased ( P < 0.05 ). Moreover, pathological observation illustrated amelioration of cartilage degeneration and joint injury. In chronic toxicity experiment of rats, SHM at 60 mg/kg demonstrated the safety. SHM had an anti-inflammatory effect through a synergistic combination of active phytochemicals to attenuate pain and cartilage degeneration by inhibiting TLR-4 and NF-κB activation. This study provided the experimental foundation for the development of SHM into a more effective dosage form or new drugs for OA treatment.

THE EFFECT OF EGGPLANT JUICE TO THE THICKNESS OF AORTIC WALL IN WHITE RAT

Atherosclerosis is a complex chronic disease characterized by the accumulation of lipids within arterial walls. Delphinidin-3-(p-coumaroylrutinoside)-5-glucoside (nasunin), an anthocyanin, was isolated as purple-colored crystals from eggplant peels. Nasunin protection against induced lipid peroxidation in rat. The aim of study was to determine the effect of eggplant juice to the thickness of aortic wall of white rat with atherogenic diet. This true experimental laboratoric study using control group post test design performed in white rat that placed in pharmacologic laboratory of Brawijaya University. Sampling was carried out by completely random sampling with 25 rats for the total sample. Data were processed and analyzed using SPSS 16. Statistical test using one-way ANOVA and continuing with post hoc Tukey. The result showed there was a significant effect between positive control of diet atherogenic with the dosage I (1,3 gr/3 ml), dosage II (2,6 gr/3 ml), and dosage III (5,2 gr/3 ml) of eggplant juice to aorta wall thickness (p=0,000;p<0,05) . We can conclude that the effective dosage of eggplant juice for reducing the progression of aortic wall thickening is dosage III (5,2 gr/3 ml).

Assessment of a Nano-Docetaxel Combined Treatment for Head and Neck Cancer

Objective: The combination of docetaxel (DTX) with Laser-Activated NanoTherapy (LANT), as a treatment for head and neck cancer (HNC), may enhance the therapeutic efficacy of lower doses of DTX, thereby minimizing the effective dosage, side effects and treatment times. Material and methods: Three HNSCC cell lines, Detroit 562, FaDu, and CAL 27, were treated with four combinations of DTX + LANT to evaluate DTX dose reduction and cell viability. Results: The 1 nM DTX + 5 nM LANT combination was the most effective treatment, increasing cell death over its corresponding DTX monotreatment with approximately 86.6%, 80.7%, and 92.1% cell death for Detroit 562, FaDu, and CAL 27, respectively. In Detroit 562, the 1 nM DTX + 5 nM LANT combination treatment resulted in the highest percentage of DTX dose reduction at 84.6%; in FaDu and CAL 27, the 0.5 nM DTX + 5 nM LANT combination treatment resulted in the highest percentage of DTX dose reduction at 78.2% and 82.4%, respectively. Conclusion: LANT may increase the therapeutic efficacy of DTX at significantly lower doses, which could improve patient outcomes.

Development and Validation of an HPLC Method for Analysis of Topotecan in Human Cerebrospinal Fluid and Its Application in Elimination Evaluation of Topotecan after Intraventricular Injection

Intrathecal administration of anticancer drugs is an effective dosage strategy, but the elimination of intraventricular drugs is not uniform in all patients. For safety, a system to evaluate local pharmacokinetics in the ventricles after administration is desired. In this study, we developed a simple and reproducible method to measure topotecan concentration in the cerebrospinal fluid (CSF) and confirmed its clinical applicability. High-performance liquid chromatography (HPLC) analysis was performed using a C18 column to measure the total topotecan concentration in the CSF. Clinical CSF samples were obtained from a 1-year old child with poor CSF absorption and stagnation. The patient received topotecan via an intraventricular subcutaneous reservoir. The HPLC method complied with the validation criteria. The lower limit of quantitation of this method was 0.04 µM. Using the developed method, we could determine the difference in topotecan CSF concentrations at 24 and 48 h after administration. The patient’s topotecan elimination rate was extremely low, and signs of adverse effects were observed at high CSF concentration of topotecan. The developed method could detect the delay in topotecan elimination after intrathecal injection. The findings of this study are valuable for the development of personalized treatments for the intrathecal administration of anticancer drugs.

Dose optimization study for recombinant tissue plasminogen activator in acute ischemic stroke: A study from Middle-East

Background: Variable intravenous recombinant tissue-plasminogen activator (rt-PA) dosages are used for ischemic stroke. We aimed to report our experience from administering different rt-PA doses in a tertiary referral center in Middle-East. Method: Medical documents of ischemic stroke patients who received rt-PA were retrospectively reviewed and analyzed. Patients were grouped into three categories based on the received total amount of rt-PA and their body weight: 0.6 mg/kg (low-dose), 0.75 mg/kg (intermediate-dose), and 0.9 mg/kg (high-dose). During the hospitalization period, patients were under full surveillance for rt-PA complications. The validated format of the National Institutes of Health stroke scale (NIHSS) and the modified Rankin scale (mRS) were used at the baseline, at the time of being discharged, and after 3 months. Chi-square, ANOVA, and ANCOVA were used for statistical analysis. Results: 602 patients were evaluated and grouped as follow: 187 (31.06%) in 0.6 mg/kg group (61% male) with mean age of 68±15 years, 217 (36.04%) in 0.75 mg/kg group (59% male) with mean age of 67±13 years, and 198 (32.89%) in 0.9 mg/kg group (50% male) with mean age of 69±17 years. There was no significant difference between the three groups regarding their demographics, comorbidities, and the distribution of stroke risk factors. No significant difference was seen between the three groups regarding in-hospital death and intracranial hemorrhage (p=0.07 and 0.09, respectively). In terms of NIHSS, no significant difference was observed between the three groups at the time of admission, discharge, and follow-up (p=0.98, 0.85, and 0.47, respectively). At the time of discharge, the mRS of 0.6 mg/kg group was significantly higher than the other two groups (p=0.04), which decreased in the 3-month follow-up and did not make significant differences (p=0.38). Conclusions: According to the in-hospital mortality, intracranial hemorrhage, mRS, and NIHSS scores, we recommend 0.75 mg/kg as our safe, beneficial, and cost-effective dosage.

P14.88 Management of primary CNS lymphomas. Experience of 32 cases

BACKGROUND Lymphomas (primary and secondary) are rare tumors of the central nervous system. They can involve both the supratentorial areas and the posterior cranial fossa. Modern management of patients with suspected CNS lymphoma should include a stereotactic or navigation-guided biopsy and subsequently carrying out chemotherapy and, in rare cases, radiosurgery. MATERIAL AND METHODS We analyzed our experience of the diagnosis and treatment of PCNSL. Our work included 32 patients with PCNSL. The study did not include patients with suspected CNS lymphoma, according to MRI data, in whom the diagnosis was not confirmed after biopsy. RESULTS Thirty patients underwent biopsy (20 - navigation guided, 1 - open, 9 - “burr hole”) with preliminary intraoperative histological verification. Gross total resection was performed in 2 cases since, according to preoperative MRI data, it was assumed that the patient had glial tumors. Postoperative histological examination confirmed the diagnosis of CNS lymphoma in all cases. Subsequently, after detailed histological and immunohistochemical studies, 30 patients underwent intra-arterial chemotherapy or high-dose chemotherapy according to NCCN protocols. Palliative treatment was recommended in 2 cases due to acute deterioration of patients. In our work, we would like to present a diagnostic algorithm and treatment regimens used in the management of our patients. CONCLUSION In the treatment of CNS lymphomas, careful histological verification is required, which is possible if several key points are performed - discontinuation of dexamethasone at least 24 hours before the biopsy, MRI for intraoperative neuronavigation after discontinuation of dexamethasone, intraoperative preliminary histological verification. In our opinion, complete removal of the tumor is possible if there are no risks of developing a persistent neurological deficit. Various methods of opening the blood-brain barrier are currently used, which can significantly reduce the effective dosage of drugs and, accordingly, the side effects. Further research is needed to determine the dependence of the prognosis of the disease on the type of surgery (biopsy or resection).