Sub–acute oral toxicity study of methanol leaves extract of Catharanthus roseus in rats

ObjectiveTo examine the sub-acute (14 d) oral toxic effects of methanol leaves extract of Catharanthus roseus (C. roseus) (Family: Apocynaceae) on liver and kidney functions in Sprague Dawley (SD) rats.MethodsTwenty four female SD rats were used throughout the experiment. The first group was orally treated with distilled water and served as control, whereas the remaining three groups were orally treated with single dose daily of 0.1 g/kg, 0.5 g/kg, 1 g/kg of C. roseus extract, respectively for 14 d. Cage-side observations were done daily. Any animal died during the experiment was dissected for gross organ examination. Body weight changed, food consumption and water intake were recorded weekly. Blood was collected via cardiac puncture on day-15 and used for determination of serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine and urea. The relative organ weights were also measured. All results were expressed as mean ± S.E.M and analysed using Dunnett's test. The level of significance was set at P<0.05 when compared to the control group.ResultsRepeated oral administration of 0.5 g/kg and 1 g/kg of methanol leaves extract of C. roseus caused mortality and diarrhoea in rats after few days of treatment. There were no significant changes observed in serum biochemical markers, body weight changed, water and food intake and relative organ weight in rats treated with a single dose daily of 0.1 g/kg of C. roseus extract treatment for 14 d when compared to control group.ConclusiondsFourteen days repeated oral administration of 0.1 g/kg of methanol leaves extract of C. roseus was safe in female SD rats without causing any significant damages to liver and kidney.     

Adjuvant chemotherapy and acute toxicity in hypofractionated radiotherapy for early breast cancer

AIM: To evaluate the effect of chemotherapy to the acute toxicity of a hypofractionated radiotherapy(HFRT) schedule for breast cancer. METHODS: We retrospectively analyzed 116 breast cancer patients with T1, 2N0 Mx. The patients received3-D conformal radiotherapy with a total physical dose of 50.54 Gy or 53.2 Gy in 19 or 20 fractions according to stage, over 23-24 d. The last three to four fractions were delivered as a sequential tumor boost. All patients were monitored for acute skin toxicity according to the European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group criteria. The maximum monitored value was taken as the final grading score. Multivariate analysis was performed for the contribution of age, chemotherapy and 19 vs 20 fractions to the radiation acute skin toxicity.RESULTS: The acute radiation induced skin toxicity was as following: grade Ⅰ 27.6%, grade Ⅱ 7.8% and grade Ⅲ 2.6%. No significant correlation was noted between toxicity grading and chemotherapy(P = 0.154, χ2 test). The mean values of acute toxicity score in terms of chemotherapy or not, were 0.64 and 0.46 respectively(P = 0.109, Mann Whitney test). No significant correlation was also noted between acute skin toxicity and radiotherapy fractions(P = 0.47, χ2test). According to univariate analysis, only chemotherapy contributed significantly to the development of acute skin toxicity but with a critical value of P = 0.05. However, in multivariate analysis, chemotherapy lost its statistical significance. None of the patients during the 2-years of follow-up presented any locoregional relapse.CONCLUSION: There is no clear evidence that chemotherapy has an impact to acute skin toxicity after an HFRT schedule. A randomized trial is needed for definite conclusions.     

Pharmacokinetics and safety of capmatinib with food in patients with MET-dysregulated advanced solid tumors

PurposeIn the Phase II GEOMETRY mono-1 study, the potent and selective mesenchymal-epithelial transition (MET) inhibitor capmatinib exhibited considerable efficacy in MET exon 14 skipping (METex14)–mutated metastatic non–small cell lung cancer at a dose of 400 mg BID. The current recommended dose is 400 mg BID in tablet formulation, with or without food. This article reports the pharmacokinetic (PK) profile, safety, and tolerability of capmatinib 300 and 400 mg BID given with food in MET-dysregulated advanced solid tumors.MethodsThis multicenter, open-label, Phase I study enrolled adult patients with MET-dysregulated advanced solid tumors. In the dose escalation phase, capmatinib tablets were orally administered at a dose of 300 mg BID with food; if tolerated, the dose escalation cohort of 400 mg BID was to be opened to enrollment. In the expansion phase, patients were to be enrolled at the higher of the tolerated doses. Tablets were taken within 30 minutes of an unrestricted meal type, except on cycle 1 day 1 (C1D1) and cycle 1 day 7 (C1D7), when they were given with a high-fat meal. The primary objectives were to determine the higher of the tolerated study doses and assess PK variables, with a secondary objective of safety.FindingsOverall, 35 patients (300 mg BID, n = 8; 400 mg BID, n = 27) with MET-dysregulated advanced solid tumors were enrolled; all patients had received prior antineoplastic therapy, and the most common primary site was lung (45.7%). Among PK-evaluable patients, the median T_max for capmatinib after administration with a high-fat meal (on C1D1/C1D7) was 4.0 to 5.6 hours across doses. At steady state (C1D7), capmatinib accumulation was low across dose levels (geometric mean of accumulation ratios, 1.29–1.69), with an increase in exposure (AUC_tau and C_max) from 300 to 400 mg BID. There were no occurrences of dose-limiting toxicity. All patients experienced at least 1 adverse event, and treatment-related adverse events occurred in 28 patients (80%; 300 mg BID, n = 6; 400 mg BID, n = 22), the most frequent of which were fatigue (37.1%) and nausea (34.3%).ImplicationsCapmatinib tablet formulation at a dose of up to 400 mg BID with food is well tolerated in patients with MET-dysregulated advanced solid tumors, with safety observations consistent with the existing profile under fasted conditions. These findings support the capmatinib dosing recommendation of 400 mg BID with or without food. ClinicalTrials.gov identifier: NCT02925104.     

Irinotecan dose reduction in metastatic colorectal cancer patients with homozygous UGT1A1*28 polymorphism: a single-center case series

ObjectiveThe UGT1A1*28 polymorphism reduces UGT1A1 enzymatic activity, which may increase the risk of severe toxicity in patients who receive standard-dose irinotecan, such as severe neutropenia and diarrhea. This real-world study assessed the optimal irinotecan dose in terms of efficacy and toxicity in metastatic colorectal cancer (mCRC) patients homozygous for the UGT1A1*28 polymorphism and receiving FOLFIRI plus bevacizumab or cetuximab as first-line therapy.MethodsWe analyzed toxicity and treatment outcomes in seven mCRC patients who were homozygous for UGT1A1*28 and received FOLFIRI plus bevacizumab or cetuximab, with an initial irinotecan dose of 120 mg/m².ResultsSix of the seven patients tolerated 120 mg/m² irinotecan without requiring dose reductions in subsequent cycles. The overall response and disease control rates were 43.0% (3/7) and 71.4% (5/7), respectively. The median progression-free survival and overall survival were 11.0 and 33.0 months, respectively. Only one severe adverse event, grade III neutropenia (2.5%), was observed.ConclusionsmCRC patients homozygous for the UGT1A1*28 allele can tolerate irinotecan at an initial dose of 120 mg/m² with favorable oncological outcomes and toxicity profiles. Further prospective studies are warranted to optimize irinotecan-based chemotherapy in these patients.     

Vitamin D and selenium blood levels and acute skin toxicity during radiotherapy for breast cancer

ObjectivesVitamin D blood levels have been shown to influence acute chemotherapy toxicities. Therefore, it was investigated whether it is an intrinsic factor influencing acute skin toxicity in patients receiving radiotherapy for breast cancer.Design/settingIn a total of 107 patients receiving radiotherapy for resected breast cancer, vitamin D and selenium blood levels were determined. Correlations between these levels and skin toxicity due to radiotherapy (CTC scores, Skindex scores) were investigated as primary endpoints. Furthermore, the statistical relationship between skin toxicity, vitamin D and selenium blood levels with patient and disease characteristics such as tumor stage, breast size, skin thickness, blood cell counts as well as individual quality of life measured by SEIQoL-Q was analyzed.Main outcome measures/resultsIn our patient collective large deficiencies of vitamin D (mean level 20.9 ng/ml, normal range 36–60 ng/ml) and selenium (mean level 76.1 μg/l, normal range 74–139 μg/l) were found. No correlations between skin toxicities, vitamin D and selenium blood levels were found. Neither did these blood levels correlate with any tumor or patient characteristics nor with individual quality of life. As expected by clinical experience, skin toxicities correlated significantly with breast size and skin thickness.ConclusionsIn this study, radiotherapy skin toxicity was not influenced by vitamin D or selenium blood levels. On the basis of our data we cannot recommend vitamin D or selenium supplementation as a prophylaxis for skin toxicity. Nevertheless, large numbers of breast cancer patients have substantial deficiencies of both substances. Therefore, supplementation may be reasonable for other reasons.     

In-vivo evidence of nephrotoxicity and altered hepatic function in rats following administration of diglycolic acid,a metabolite of diethylene glycol

Context: Diglycolic acid (DGA) is one of the two primary metabolites of diethylene glycol (DEG). DEG is an industrial solvent that has been implicated in mass poisonings resulting from product misuse in the United States and worldwide, with the hallmark toxicity being acute kidney injury, hepatotoxicity, encephalopathy and peripheral neuropathy. Our laboratory has generated in-vitro evidence suggesting that DGA is the metabolite responsible for the proximal tubule necrosis and decreased kidney function observed following DEG ingestion. Furthermore, we have shown that DGA specifically accumulates in kidney tissues (100× higher than peak blood concentrations) following DEG administration.

Objective: To examine renal and hepatic accumulation and dysfunction following direct administration of DGA in-vivo. We hypothesize that administration of DGA will result in renal and hepatic DGA accumulation, as well as proximal tubular necrosis and liver injury.

Materials and methods: Adult male Wistar rats were divided into three groups dosed with 0, 100 or 300?mg/kg DGA via single oral gavage. Urine was collected every 6–12?h and blood, kidneys and liver were removed upon sacrifice at 48?h post-dosing for analysis.

Results: DGA accumulated significantly in both kidney and liver tissue only at 300?mg DGA/kg. DGA concentrations in the kidneys and liver correlated with renal and hepatic injury, respectively. Histopathological and clinical chemistry analysis revealed that DGA-treated animals exhibited moderate liver fatty accumulation and marked renal injury, again only at 300?mg/kg.

Discussion: DGA-induced kidney injury demonstrated a steep dose response threshold, where severe damage occurred only in animals given 300?mg/kg DGA, while no toxicity was observed at 100?mg/kg.

Conclusion: These results provide evidence for in-vivo toxicity following direct administration of DGA, a metabolite of DEG. The steep dose–response threshold for toxicity suggests mechanistically that there is likely a saturable step that results in DGA accumulation in target organs.     

银杏红曲维生素组方调脂有效性与安全性研究

目的探讨银杏红曲维生素组方(MGM)对混合型高脂血症大鼠血脂水平的影响及其急性毒性。方法采用混合型高脂血症SD大鼠模型,灌胃给予25 mg/kg、50 mg/kg剂量的MGM和阳性对照品32 d后,评价MGM的调脂效果。采用最大耐受剂量法评价23.2 g/(kg·d)的MGM单次给药72 h后对BALB/c小鼠与SD大鼠2种啮齿类动物的急性毒性。结果 MGM及阳性对照品给药32 d后较给药前显著降低高脂血症大鼠总胆固醇、甘油三酯和LDL-C的含量(P均<0.001),其中25 mg/kg的MGM的调脂效果与50 mg/kg剂量的阳性对照品相当,表明MGM的复方优于阳性对照品的调脂效果。急性毒性实验结果显示MGM对大、小鼠的最大耐受剂量为23.2 g/(kg·d),相当于人体推荐口服剂量的1933倍,在该剂量下观察小鼠与大鼠心脏、肝脏、肾脏的病理切片结果未发现损伤性病变。结论 MGM显著降低高脂血症大鼠的血脂水平,在推荐量范围内服用MGM安全可靠。     

实时剪切波弹性成像技术评价下肢深静脉血栓

目的 应用实时剪切波弹性成像（SWE）技术定量评估不同时期下肢深静脉血栓（DVT）弹性的变化。方法 选取71例经常规超声诊断为下肢DVT的患者,根据发病时间和超声图像特点分为急性期组、亚急性期组和慢性期组;应用SWE超声诊断仪测量各组患者下肢DVT的平均杨氏模量值,并进行统计学分析。结果 急性期、亚急性期、慢性期组平均杨氏模量值分别为（7.65±1.69）kPa、（14.41±2.36）kPa和（26.16±4.07）kPa,3组间差异有统计学意义（F=267.558,P<0.01）。结论 SWE技术可定量不同时期下肢深静脉血栓的平均杨氏模量值范围,为选择治疗方案和评估肺栓塞风险提供重要依据。     

Green synthesis of gold nanoparticles from Manilkara zapota L. extract and the evaluation of its intrinsic in vivo antiarthritic potential

The plant Manilkara zapota belongs to the family Sapotaceae and is commonly known as Chiku in Pakistan. Traditionally, M. zapota is used in pulmonary diseases, diarrhea, rheumatism, hemorrhage, and ulcers. There is no study available on the in vivo antiarthritic activity of M. zapota and its gold nanoparticles (AuNPs). The aim of this study is to evaluate the in vivo acute and sub-acute antiarthritic activity of aqueous extract of M. zapota and its biosynthesized gold nanoparticles (AuNPs). Plant-induced reduction method was used for the synthesis of AuNPs. The synthesized AuNPs were characterized via UV, FTIR, SEM, and zeta potential measurements and were optimized by screening various parameters including time, temperature, pH, and salt concentration. Arthritis in rats was induced by Freund''s Complete Adjuvant (FCA) injection in hind paw. The antiarthritic effect was evaluated by the determination of paw volume, joint diameter, latency time, hematological, biochemical parameters, antioxidant biomarkers, TNF-α level, and radiological evaluation. The aqueous extract and nanoparticles significantly decreased the paw volume, joint diameter, and significantly increased latency time as compared to the FCA-induced arthritic group. They significantly normalized the hematological, biochemical parameters, and oxidative stress biomarkers in comparison to the arthritic group. They also significantly decreased the TNF-α level when assessed against the arthritic group. Radiological evaluation confirmed the antiarthritic effect of the aqueous extract and nanoparticles of M. zapota leaf extract. It is concluded that the aqueous extract and nanoparticles of M. zapota possess significant analgesic, antiarthritic, and anti-inflammatory activity. However, nanoparticles possess more pronounced antiarthritic activity as compared to the aqueous extract. Moreover, free radical scavenging action and TNF-α reduction showed a prominent role in their antiarthritic activity. Further, investigation is underway to identify the active phytochemical constituent responsible for the antiarthritic activity.

The aim of this study is to evaluate the in vivo acute and sub-acute antiarthritic activity of aqueous extract of M. zapota and its biosynthesized gold nanoparticles (AuNPs).     

Acute and sub-acute toxicities of hydroalcoholic extract of Allium affine aerial parts in rats

Objective:To assess the potential toxicity of hydroalcoholic extract of Allium affine(A.affine)aerial parts after acute and sub-acute administration in female and male Wistar rats.Methods:For acute toxicity assay,animals orally received the limit test dose of 2000 mg/kg of A.affine extract and were observed for 2 weeks.For sub-acute toxicity study,rats were orally treated with 125,250,and 500 mg/kg/day of the extract over 28 days,and hematological,biochemical,and histological evaluations were then conducted.Results:All rats were alive with normal body weight gain over 14 days,with LD50˃2000 mg/kg.No abnormality in body weight changes but significant increases in the relative weight of spleen and lung were detected after administration of the highest dose of extract for 28 days in sub-acute assay.Hematological analysis showed prominent elevations in total white blood cells in male rats and neutrophils count in female rats after exposure to 500 mg/kg of A.affine extract.In biochemical evaluations,significant increases in serum creatinine level(female rats,250 and 500 mg/kg)and in aspartate aminotransferase(male and female rate,500 mg/kg)and alanine aminotransferase(male,250 and 500 mg/kg and female,500 mg/kg)activities,however,notable decreases in serum blood glucose(male rats,125 and 500 mg/kg),triglycerides(male rats,500 mg/kg and female rates,250 mg/kg),and low-density lipoprotein cholesterol levels(male,250 mg/kg)were found.Histological examinations presented slight portal inflammation in liver tissue,moderate pneumocyte hyperplasia,congestion and peri-bronchial inflammation in lung tissue,and mild histiocytosis and lymphoid follicular activation in spleen tissue after exposure to 500 mg/kg of A.affine extract in male and female animals.Conclusions:The present investigation reveals the safety of A.affine extract at doses of lower than 250 mg/kg in rats and monitoring of lung,spleen,and liver functions is suggested during excessive and prolonged uses.     

Peg-asparaginase for acute lymphoblastic leukemia

Importance of the field: Asparaginase is a prominent component of pediatric and adolescent treatment for acute lymphoblastic leukemia. These treatment regimens are now being employed in adults. Knowledge of the efficacy and toxicity of asparaginase preparations is essential when using these treatments.

Areas covered by this review: The search terms used were asparaginase, leukemia, pegylated, oncaspar, adolescent and young adult. Literature was searched in Pubmed/Medline with no limitations on year of publication. Abstracts from the American Society of Hematology meetings and the American Society of Clinical Oncology were searched from 2004 – 2008 using the same terms.

What the reader will gain: The reader will gain knowledge of the tolerability and efficacy of pegylated asparaginase when treating acute lymphoblastic leukemia.

Take home message: Pegylated asparaginase is generally well tolerated in adult patients with efficacy that appears to be at least equivalent to native asparaginase preparations.     

Evaluation of antidiabetic effect of total calystegines extracted from Hyoscyamus albus

BackgroundHyoscyamus albus L. (Solanaceae) an old medicinal plant is a rich source of tropane and nortropane alkaloids which confers to this plant a number of very interesting and beneficial therapeutic effects.PurposeCalystegines that are polyhydroxylated alkaloids and imino-sugars poccess significant glycosidases inhibitory activities and are therefore good candidats for the treatment of diabetes mellitus.Study designCalystegines extracted from Hyoscyamys albus seeds were tested for teir acute oral toxicity and investigated for their in-vivo antidiabetic effect on Streptozotocine induced diabetes in mice.MethodesCalystegines were extracted from the seeds plant using an Ion exchange column; the remaining extract was then administrated orally to mice at several single doses for acute toxicity assay. A dose of 130 mg/kg streptozotocine was injected to mice to induce diabetes mellitus, and diabetic mice were treated orally during 20 days with 10 mg/kg and 20 mg/kg calystegines and 20 mg/kg glibenclamide as the reference drug.ResultsAcute oral toxicity showed that calystegines are not toxic up to a dose of 2000 mg/kg with absence of any signs of intoxication and damages in Liver and kidney tissues.The nortropane alkaloids markedly reduced blood glucose levels and lipid parameters of diabetic mice to normal concentrations after 20 days of treatment at 10 mg/kg and 20 mg/ kg (p < 0.05). Histopathological study of diabetic mice pancreas indicated that calystegines of Hyoscyamus albus have minimized streptozotocine damages on β-cells of islets of langerhans, stimulated β-cells regeneration and improved with this insulin secretion.ConclusionThe findings of this study suggest that calystegines are potent antidiabetic agents with antihyperglicemic and hypolipidemic effects, and a protective fonction on pancreas in streptozotocin induced diabetes in mice.     

Knee extensor muscles strength indicates global lower-limb strength in individuals who have suffered a stroke: A cross-sectional study

ObjectivesThis study had three aims: (1) to evaluate the relationships between the paretic knee extensor muscle strength and global lower-limb strength in individuals who had suffered a sub-acute/chronic stroke, (2) to determine whether global lower-limb strength, sex, body mass index, or age could predict knee extensor muscle strength, and 3) to investigate whether the results obtained via a Modified Sphygmomanometer Test (MST) would be similar to those obtained using a hand-held dynamometer.MethodsThis was a cross-sectional study, performed at a research laboratory, at participants’ homes, or at outpatient clinics. Forty-two individuals with a sub-acute stroke and 45 individuals with a chronic stroke participated. Maximum isometric strength of the paretic lower-limb muscles (i.e. hip, knee, and ankle flexors/extensors, hip abductors) was measured using the MST and a hand-held dynamometer.ResultsSignificant and high correlation coefficients were found between knee extensor muscle strength and global lower-limb strength as measured by the combined strength values of 6 lower limb muscle groups in individuals with sub-acute (0.81 ≤ r ≤ 0.88; p < 0.05) and chronic (0.82 ≤ r ≤ 0.85; p < 0.05) stroke. Step-wise multiple regression analysis revealed that only global lower-limb strength was retained in the model and accounted for 66–78% and 67–72% (p < 0.001) of the variance in knee extensor muscle strength at the sub-acute and chronic phases post-stroke, respectively. The results obtained via the MST were similar to those obtained using the hand-held dynamometer.ConclusionParetic knee extensor muscles strength, assessed using a MST or a hand-held dynamometer, indicates global lower-limb strength in individuals with a sub-acute or chronic stroke.     

Comparison of lower-dose versus higher-dose intravenous naloxone on time to recurrence of opioid toxicity in the emergency department

Introduction: The initial dose of naloxone administered to patients who present to the emergency department (ED) with opioid overdose is highly variable. The objective of this study was to determine if the initial dose of intravenous (IV) naloxone given to these patients was associated with the time to recurrence of opioid toxicity.

Methods: This was a multicenter retrospective cohort study, conducted at two academic EDs in the United States. Consecutive adults who had a positive response to naloxone for opioid overdose in the ED were included. Patients were categorized into two groups based on initial IV naloxone dose administered: 0.4?mg (lower-dose) or 1–2?mg (higher-dose). The main outcome measure was the time to recurrence of opioid toxicity requiring a second dose of naloxone. Secondary outcomes included the need for naloxone continuous infusion and adverse events.

Results: The study included 84 patients with 42 patients receiving lower-dose and 42 patients receiving higher-dose naloxone. Median time to re-dose of naloxone was similar between the lower-dose (72 [IQR 46–139] minutes) and higher-dose (70 [IQR 44–126] minutes) groups (p=.810). There were 12 patients (29%) in the lower-dose group and 17 patients (41%) in the higher-dose group who subsequently required continuous infusions (p=.359). The proportion of patients with adverse events was similar between lower-dose and higher-dose groups (31% versus 41%, p=.495). There was no difference in the incidence of specific withdrawal related adverse effects.

Conclusions: The initial dose of naloxone given to patients in the ED does not influence the time to recurrence of opioid toxicity.     

肺动脉栓塞不同时相的尿激酶溶栓疗效观察的实验研究

目的探讨肺动脉栓塞不同时相的尿激酶溶栓的疗效。方法成功制作11头小型猪肺动脉栓塞实验模型(另1头死于出血性肺梗死),以尿激酶作为溶栓剂,观察在栓塞不同时相(栓塞术后30min、栓塞术后10天、术后30天)的溶栓治疗效果。结果实验小型猪在肺动脉栓塞急性期(3头次)以尿激酶15×104U溶栓治疗后被栓塞肺动脉恢复通畅;亚急性期(3头次)以30×104U尿激酶后得到同样结果;慢性期(3头次)以50×104U尿激酶溶栓后,肺动脉三级分支内的血栓完全溶解,再追加5×104U尿激酶,肺动脉四级分支内血栓明显减少。结论肺动脉栓塞不同时相的尿激酶溶栓治疗均有一定的疗效,急性期和亚急性期较慢性期的疗效好,不同时相的溶栓治疗所需尿激酶剂量随栓塞时间延长而呈递增趋势。     

Nephroprotective and antioxidant properties of Artemisia arborescens hydroalcoholic extract against oestroprogestative-induced kidney damages in rats

ObjectiveCurrently, medicinal plants are found to have biological and pharmacological activities and are used in various domains. This study, carried out on Wistar rats, evaluates the beneficial effects of Artemisia arborscens extract on oestroprogestative-induced damages in kidney.Materials and methodsThirty-six 3-month-old Wistar rats were divided into 4 batches of nine each: a control group, a group of rats receiving oestroprogestative treatment, a group undergoing oestroprogestative treatment after receiving Artemisia arborescens extract in drinking water, and a group that received only Artemisia arborescens.ResultsArtemisia arborescens extract was found to optimize many parameters which were shifted to pathological values as a consequence of oestroprogestative toxicity: plasma creatinine and urea levels were decreased, uric acid and proteins were restored to normal values. The alteration of renal architecture was also suppressed. In addition, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities that had been reduced in kidney of the treated group were restored by Aretmisia arborscens-based treatments and, therefore, the lipid peroxidation level was reduced in the renal tissue compared to the control group.ConclusionThe obtained results confirmed that the Artemisia-based treatment allowed efficient protection against oestroprogestative-induced nephrotoxicity by restoring the activities of kidney. The protective effect of Artemisia arborescens was mainly attributed to antioxidant properties as well as the presence of phenolic acids and flavonoids detected by means of HPLC.     

Single dose dexamethasone prophylaxis of postembolisation syndrome after chemoembolisation in hepatocellular carcinoma patient: A randomised,double-blind,placebo-controlled study

BACKGROUNDEven in the immuno-oncology era, transcatheter arterial chemoembolisation (TACE) is the most effective way to treat intermediate stage hepatocellular carcinoma (HCC). Postembolisation syndrome (PES) is the most common side effect from TACE and there is still no standard prevention guideline.AIMTo evaluate the efficacy of single dose intravenous dexamethasone regimen to prevent PES after TACE among patients with HCC. METHODSThis study enrolled patients with HCC who had eligible indication for TACE without macrovascular invasion/extrahepatic metastasis. Patients were randomly assigned to either an intravenous single dose of dexamethasone 8 mg or placebo one hour before TACE. The primary outcome was a negative result of PES at 48 h after TACE, which was defined as score < 2 of Southwest Oncology Group toxicity coding criteria using fever, nausea, vomiting and pain to calculated. And the secondary end point was duration of admission between two groups.RESULTSOne hundred patients were randomly assigned 1:1. Under intention-to-treat analysis, 49 patients were randomly assigned to the dexamethasone and 51 to the placebo groups. Both groups were similar for baseline characteristics. The negative PES rate was significantly higher in the dexamethasone group than in the placebo group (63.3% vs 29.4%; P = 0.005). Mean Southwest Oncology Group toxicity coding PES was 2.14 (95%CI: 1.41-2.8) vs 3.71 (95%CI: 2.97-4.45) between the dexamethasone and placebo groups, respectively. Cumulative incidence of fever was significantly lower in dexamethasone group with P < 0.001, pain, nausea and vomiting were also lower in the dexamethasone group compared with the placebo group (P = 0.16, P = 0.11, and P = 0.49). The dexamethasone regimen was generally well tolerated by patients with HCC patients including those with hepatitis B virus infection and well-controlled diabetes mellitus.CONCLUSIONSingle dose dexamethasone was effective at preventing PES among patients with HCC treated with TACE. The study showed no adverse events of special interest related to dexamethasone.     

Acute Toxicity Evaluation of Glycosylated Gd<Superscript>3+</Superscript>-Based Silica Nanoprobe

Purpose

Early stage diseases diagnosed using magnetic resonance imaging (MRI) techniques is of high global interest as a potent noninvasive modality. MRI contrast agents are improved through modifications in structural and physicochemical properties of the applied nanoprobes. But, the potential toxic effects of nanoprobes upon exposure to biological systems are still a major concern.

Procedure

In this study, the acute toxicity of glycosylated Gd³⁺-based silica mesoporous nanospheres (GSNs) as a MRI contrast agent was evaluated in Balb/c mice. In order to evaluate in vivo toxicity of GSN, preclinical studies, daily weight monitoring, hematological/blood chemistry tests, and histological assessment were conducted. Magnetic resonance relaxivities of GSN was determined using a MRI scanner.

Results

The obtained results suggest that in vivo toxicity of GSN was mostly influenced by nanoparticle surface area, functionality, and nanoparticle zeta potential. The maximum tolerated dose (MTD) increased in the following order: mesoporous silica nanospheres (MSNs) at 1 mg/mice < GSN (aspect ratio 1, 2, 8) at 40 mg/mice. The results also indicate GSN, one of the best cell imaging contrast agent, which does not show any significant toxicity on multiple vital organs following injection of 20 mg/mice, while a significant T₁-weighted enhancement was observed in whole body of a Balb/c mice 15 min postinjection of (5 μmol/kg) of body weight of GSN.

Conclusions

These results shed light on the functionality of MSNs to minimize in vivo toxicity. Also, glyconanoprobe can be beneficially used for nanomedicine and cellular imaging applications without any significant toxicity.

     

Phase I study of intraperitoneal bevacizumab for treating refractory malignant ascites

ObjectiveThis prospective, dose-escalation phase I study evaluated the safety and efficacy of intraperitoneal bevacizumab in managing refractory malignant ascites and explored the recommended dose of bevacizumab for further study.MethodsPatients with refractory malignant ascites were enrolled. Bevacizumab was intraperitoneal administered weekly at an initial dose of 2.5 mg/kg, with dose escalation to 5 and 7.5 mg/kg performed following the standard “3 + 3” rule. The total duration of treatment was 2 or 3 weeks.ResultsBetween December 2013 and September 2014, 13 patients (2.5 mg/kg, n = 4; 5 mg/kg, n = 3; 7.5 mg/kg, n = 6) with refractory malignant ascites were enrolled. Bevacizumab was well tolerated, and the most common treatment-related adverse events were abdominal pain (5/13), abdominal distension (2/13), and fatigue (2/13). The dose-limiting toxicity at 7.5 mg/kg was grade 3 bowel obstruction (1/13). The maximum tolerated dose (MTD) was not reached. The overall response and disease control rates were 7.7 and 61.5%, respectively.ConclusionsIntraperitoneal bevacizumab safe and well tolerated for treating malignant ascites, and the MTD was not reached at doses of 2.5 to 7.5 mg/kg. Intraperitoneal bevacizumab at 7.5 mg/kg weekly is recommended for further study to verify its anti-tumor activity.Trial registration: Clinical Trials {"type":"clinical-trial","attrs":{"text":"NCT01852409","term_id":"NCT01852409"}}NCT01852409.