调营饮对小鼠S180肝癌腹水模型腹膜淋巴孔直径、面积、周长及密度的影响

目的探讨调营饮对小鼠S180肝癌腹水模型腹膜淋巴孔的影响。方法取S180细胞接种于小鼠腹腔造成肝癌腹水模型,随机分为空白对照组（NS）、模型组（M）、调营饮低剂量组（TA）、调营饮高剂量组（TB）、模型＋NO供组（NO）、调营饮高剂量组＋NOS抑制剂组（NOS）,造模后第5d用调营饮连续灌胃,观察对小鼠腹膜淋巴孔的影响。结果 TA组和TB组腹膜淋巴孔的平均周长、平均面积和平均密度均明显大于NS组和M组（P〈0.01）,NO组腹膜淋巴孔平均周长、平均面积和平均密度明显大于相对应的M组（P〈0.01）,NOS组的腹膜淋巴孔平均周长、平均面积和平均密度明显少于相对应的TB组（P〈0.01）,TA与TB组比较差异无统计学意义（P〉0.05）。结论调营饮对小鼠S180肝癌腹水模型有明显促进腹膜淋巴孔开放面积增大、周长和分布密度增加的作用,可能是其消腹水作用机制之一。     

Treatment of Vitamin D Deficiency with Calcifediol: Efficacy and Safety Profile and Predictability of Efficacy

Calcifediol (25-OH-vitamin D3) is the prohormone of the vitamin D endocrine system. It is used to prevent and treat vitamin D deficiency. Calcifediol, as well as cholecalciferol (vitamin D3), is efficient and safe in the general population, although calcifediol has certain advantages over cholecalciferol, such as its rapid onset of action and greater potency. This review analyzed studies comparing the efficacy and safety of both calcifediol and cholecalciferol drugs in the short and long term (>6 months). Calcifediol was found to be more efficacious, with no increase in toxicity. We also assessed the predictability of both molecules. A 25OHD increase depends on the dose and frequency of calcifediol administration. In contrast, after cholecalciferol administration, 25OHD increase depends on more factors than dose and frequency of administration, also phenotypic aspects (such as obesity and malabsorption), and genotypic factors impacts in this increase.     

多柔比星脂质体注射液与多柔比星注射液大鼠重复给药毒性的比较

目的研究大鼠连续静脉注射给予多柔比星脂质体注射液和多柔比星注射液后对大鼠产生的毒性作用及毒性异同比较。方法 SD大鼠90只,随机分为溶剂对照组、多柔比星脂质体注射液(1 mg/kg)和多柔比星注射液(1 mg/kg)组。各组大鼠每3 d静脉注射1次,连续给药13次,检测其体重、血液生化学、血液学、脏器系数等指标,并进行组织病理学检查。结果多柔比星脂质体注射液1 mg/kg可引起SD大鼠脱毛和溃疡,体重增长明显延缓,PLT、ALT、BUN升高,ALB降低,心脏和肾脏系数增大,胸腺和睾丸系数减小,组织病理学检查结果显示睾丸曲细精管生精上皮脱落,各级生精细胞消失,部分间质水肿;心脏心肌纤维断裂、溶解,横纹及部分细胞核消失;肾脏出现肾小管透明管型等病理组织学病变。与多柔比星脂质体注射液比较,相同剂量下多柔比星注射液亦可引起以上病变,但大鼠脱毛和皮肤溃疡率降低,肾脏毒性和心脏毒性明显增加。结论多柔比星脂质体注射液与普通注射液比较,心脏和肾脏毒性明显减轻,但皮肤毒性明显增加。     

Metabolic acidosis due to inhaled salbutamol toxicity: A hazardous side effect complicating management of suspected cases of acute severe asthma

Metabolic acidosis has seldom been reported during treatment of asthma with use of beta agonist but not with much clinical consequence. We report two cases of metabolic acidosis with hyperventilation as a direct effect of salbutamol that caused difficulty in assessment and management of their respiratory symptoms which resolved with appropriate tapering of beta agonist.     

Local anesthetic systemic toxicity (LAST) – Should we not be concerned?

Local anesthetics are one of the most commonly used drugs in the field of medicine. Yet little is known about the systemic toxicity that can occur with their overdose. In the last few years, a lot of research has taken place understanding the etiology of the Local anesthetics systemic toxicity (LAST) and the role of lipid emulsion in treating it. There is a need to increase the awareness about LAST and establish a protocol to treat any serious neuro or cardiotoxicity.     

Unusual radiological presentation of sirolimus-associated pneumonitis

Sirolimus-associated pneumonitis, a rare but serious drug-induced lung injury, has become a great concern clinically, because of the increasing use of sirolimus (rapamycin) in patients who have been subjected to solid organ transplantation. We report sirolimus-associated pneumonitis in two women who underwent renal transplantation. At variance with previous reports, the radiological findings shown on chest radiographs and computed tomography scans of the chest in these two cases were consolidation lesions mainly with minimal interstitial abnormalities. Our reported cases highlight that awareness of various radiological findings of sirolimus-associated pneumonitis is pivotal for physicians to make early diagnosis of the disorder in patients who have undergone solid organ transplantation.     

Role of CD4 and CD8 T-lymphocytes,B-lymphocytes and Natural Killer cells in the prediction of radiation-induced late toxicity in cervical cancer patients

Purpose:?To analyse the role of in vitro radio-induced apoptosis of lymphocyte subpopulations as predictive test for late effects in cervical cancer patients treated with radiotherapy.

Methods and materials:?Ninety-four consecutive patients and four healthy controls were included in the study. Toxicity was evaluated using the Late Effects Normal Tissue-Subjective, Objective, Management, and Analytic (LENT-SOMA) scale. Peripheral blood lymphocyte subpopulations were isolated and irradiated at 0, 1, 2 and 8 Gy, and then collected 24, 48 and 72 h after irradiation. Apoptosis was measured by flow cytometry.

Results:?Radiation-induced apoptosis increased with radiation dose and time of incubation, and data fitted to a semi-logarithmic model defined by two constants: α (percentage of spontaneous cell death) and β (percentage of cell death induced at a determined radiation dose). Higher β values in cytotoxic T-lymphocytes (CD8) and bone cells (B-lymphocytes) were observed in patients with low bowel toxicity (hazard ratio (HR)?=?0.96, p?=?0.002 for B-cells); low rectal toxicity (HR?=?0.96, p?=?0.020; HR?=?0.93, p?=?0.05 for B and CD8 subpopulations respectively); low urinary toxicity (HR?=?0.93, p?=?0.003 for B-cells) and low sexual toxicity (HR?=?0.93, p?=?0.010 for CD8-cells).

Conclusions:?Radiation-induced CD8 T-lymphocytes and, for the first time, B-lymphocytes apoptosis can predict differences in late toxicity in cervical cancer patients.     

Study of oxidative,enzymatic mitochondrial respiratory chain function and apoptosis in perinatally HIV-infected pediatric patients

Abstract

Mitochondrial toxicity in perinatally human immunodeficiency virus (HIV)-infected pediatric patients has been scarcely investigated. Limited data are available about HIV or antiretroviral (ARV)-mediated mitochondrial damage in this population group, specifically, regarding oxygen consumption and apoptosis approach. We aimed to elucidate whether a given mitochondrial DNA depletion is reflected at downstream levels, to gain insight on the pathology of HIV and highly active antiretroviral therapy (HAART) in perinatally HIV-infected pediatric patients. We studied 10 healthy control participants and 20 perinatally HIV-infected pediatric patients (10 under ARV treatment and 10 off treatment). We determined mitochondrial mass, subunits II and IV of complex IV, global and specific mitochondrial enzymatic and oxidative activities, and apoptosis from peripheral blood mononuclear cells. Global oxygen consumption was significantly compromised in HIV-infected untreated patients, compared to the control group (0.76?±?0.01 versus 1.59?±?0.15; P?=?0.014). Apoptosis showed a trend to increase in untreated patients as well. The overall complex (C) CI-III-IV activity of the mitochondrial respiratory chain (MRC) was significantly decreased in HIV-infected treated patients with respect to the control group (1.52?±?0.38 versus 6.38?±?1.53; P?=?0.02). No statistically significant differences were found between untreated and HAART-treated patients. These findings suggest the pathogenic role of both HIV and HAART in mitochondrial dysfunction in vertical infection. The abnormalities in mitochondrial genome may be downstream reflected through a global alteration of the MRC. Mitochondrial impairment associated with HIV and HAART was generalized, rather than localized, in this series of perinatally HIV-infected patients.     

Position Statement and Practice Guidelines on the Use of Multi-Dose Activated Charcoal in the Treatment of Acute Poisoning

In preparing this Position Statement, all relevant scientific literature was identified and reviewed critically by acknowledged experts using agreed criteria. Well-conducted clinical and experimental studies were given precedence over anecdotal case reports and abstracts were not usually considered. A draft Position Statement was then produced and subjected to detailed peer review by an international group of clinical toxicologists chosen by the American Academy of Clinical Toxicology and the European Association of Poisons Centres and Clinical Toxicologists. The Position Statement went through multiple drafts before being approved by the Boards of the two societies.

The Position Statement includes a summary statement for ease of use and is supported by detailed documentation which describes the scientific evidence on which the Statement is based.

Although many studies in animals and volunteers have demonstrated that multiple-dose activated charcoal increases drug elimination significantly, this therapy has not yet been shown in a controlled study in poisoned patients to reduce morbidity and mortality. Further studies are required to establish its role and the optimal dosage regimen of charcoal to be administered.

Based on experimental and clinical studies, multiple-dose activated charcoal should be considered only if a patient has ingested a life-threatening amount of carbamazepine, dapsone, phenobarbital, quinine, or theophylline. With all of these drugs there are data to confirm enhanced elimination, though no controlled studies have demonstrated clinical benefit.

Although volunteer studies have demonstrated that multiple-dose activated charcoal increases the elimination of amitriptyline, dextropropoxyphene, digitoxin, digoxin, disopyramide, nadolol, phenylbutazone, phenytoin, piroxicam, and sotalol, there are insufficient clinical data to support or exclude the use of this therapy.

The use of multiple-dose charcoal in salicylate poisoning is controversial. One animal study and 2 of 4 volunteer studies did not demonstrate increased salicylate clearance with multiple-dose charcoal therapy. Data in poisoned patients are insufficient presently to recommend the use of multiple-dose charcoal therapy for salicylate poisoning.

Multiple-dose activated charcoal did not increase the elimination of astemizole, chlorpropamide, doxepin, imipramine, meprobamate, methotrexate, phenyítoin, sodium valproate, tobramycin, and vancomycin in experimental and/or clinical studies.

Unless a patient has an intact or protected airway, the administration of multiple-dose activated charcoal is contraindicated. It should not be used in the presence of an intestinal obstruction. The need for concurrent administration of cathartics remains unproven and is not recommended. In particular, cathartics should not be administered to young children because of the propensity of laxatives to cause fluid and electrolyte imbalance.

In conclusion, based on experimental and clinical studies, multiple-dose activated charcoal should be considered only if a patient has ingested a life-threatening amount of carbamazepine, dapsone, phenobarbital, quinine, or theophylline.

This Position Statement was drafted by JA Vale, EP Krenzelok, and GD Barceloux.     

Liver Function Test Abnormalities in Users of Aqueous Kava Extracts

Abstract

Introduction.?Hepatic toxicity from manufactured herbal remedies that contain kava lactones has been reported in Europe, North America, and Australia. There is no evidence for serious liver damage in kava‐using populations in Pacific Island societies or in Indigenous Australians who have used aqueous kava extracts. This article presents evidence that liver function changes in users of aqueous kava extracts appear to be reversible. Data from one Arnhem Land community [Northern Territory (NT), Australia] with 340 indigenous people older than 15 years of age in 2000 are used. Methods.?This study was a cross‐sectional study with 98 participants, 36 of whom had never used kava. Among 62 kava users, 23 had discontinued kava at least 1 year before the study. Continuing users had not used kava for 1 to 2 months (n = 10) or 1 to 2 weeks previously (n = 15). Some (n = 14) had used kava within the previous 24 hr. Liver function tests were compared across these groups, taking into account differences due to age, sex, alcohol, and other substance use. Results.?The average quantity of kava powder consumed was 118 g/week, and median duration of use was 12 years (range, 1–18 years). Kava usage levels were less than one‐half of those found in previous studies. More recent kava use was independently associated with higher levels of liver enzymes gamma‐glutamyl transferase (GGT) (p < 0.001) and alkaline phosphatase (ALP) (p < 0.001), but not with alanine aminotransferase or bilirubin, which were not elevated. In those who were not heavy alcohol users, only those who used kava within the previous 24 hr showed GGT levels higher than nonusers (p < 0.001), whereas higher ALP levels occurred only in those who last used kava 1 to 2 weeks (p = 0.015) and 24 hr previously (p = 0.005). Discussion.?Liver function changes in users of aqueous kava extracts at these moderate levels of consumption appear to be reversible and begin to return to baseline after 1 to 2 weeks abstinence from kava. No evidence for irreversible liver damage has been found.