The Potentized Homeopathic Drug,Lycopodium clavatum (5C and 15C) Has Anti-cancer Effect on HeLa Cells In Vitro.

Cancer is a disease that needs a multi-faceted approach from different systems of medicine. The purpose of this study was to evaluate whether homeopathically-potentized ultra-high dilutions of Lycopodium Clavatum (LC-5C and LC-15C, respectively) have any anti-cancer effects on HeLa cells. Cells were exposed to either LC-5C (diluted below Avogadro's limit, i.e., 10^?10) or LC-15C (diluted beyond Avogadro's limit, i.e., 10^?30) (drug-treated) or to 30% succussed ethanol (“vehicle” of the drug). The drug-induced modulation in the percent cell viability, the onset of apoptosis, and changes in the expressions of Bax, Bcl2, caspase 3, and Apaf proteins in inter-nucleosomal DNA, in mitochondrial membrane potentials and in the release of cytochrome-c were analyzed by utilizing different experimental protocols. Results revealed that administration of LC-5C and LC-15C had little or no cytotoxic effect in normal peripheral blood mononuclear cells, but caused considerable cell death through apoptosis in cancer (HeLa) cells, which was evident from the induction of DNA fragmentation, the increases in the expressions of protein and mRNA of caspase 3 and Bax, and the decreases in the expressions of Bcl2 and Apaf and in the release of cytochrome-c. Thus, the highly-diluted, dynamized homeopathic remedies LC-5C and LC-15C demonstrated their capabilities to induce apoptosis in cancer cells, signifying their possible use as supportive medicines in cancer therapy.     

New analysis of the toxic compounds from the Androctonus mauretanicus mauretanicus scorpion venom

Scorpion venoms are very complex mixtures of molecules, most of which are peptides displaying different kinds of biological activity. Indeed, these peptides specifically bind to a variety of pharmacological targets, in particular ionic channels located in prey tissues, resulting in neurotoxic effects. Toxins modulating Na+, K+, Ca2+ and Cl(-) currents have been described in scorpion venoms. In this work, we have used several specific antibodies raised against the most lethal scorpion toxins already described to screen the Moroccan scorpion Androctonus mauretanicus mauretanicus venom in order to characterize new compounds. This immunological screening was also implemented by toxicity tests in mice and with mass spectrometry study, providing new informations on the molecular composition of this venom. In fine, we were able to determine the molecular masses of 70-80 different compounds. According to the immunological data obtained, many toxins cross-react with three sera raised against the most lethal alpha-toxins found in North African scorpion venoms, but not at all with those raised against the main beta-toxins from South and North American venoms. Some of the previously described toxins from Androctonus mauretanicus mauretanicus venom could thus be detected by combining immunological tests, toxicity in mice and molecular masses. Among these toxins, one of them, which showed a mild cross-reaction with the serum raised against AaH I (a highly potent toxin from the venom of Androctonus australis), was identified as Amm III and fully sequenced.     

Couples’ experiences with expanded carrier screening: evaluation of a university hospital screening offer

Preconception carrier screening offers couples the possibility to receive information about the risk of having a child with a recessive disorder. Since 2016, an expanded carrier screening (ECS) test for 50 severe autosomal recessive disorders has been available at Amsterdam Medical Center, a Dutch university hospital. This mixed-methods study evaluated the experiences of couples that participated in the carrier screening offer, including high-risk participants, as well as participants with a general population risk. All participants received genetic counselling, and pre- (n = 132) and post-test (n = 86) questionnaires and semi-structured interviews (n = 16) were administered. The most important reason to have ECS was to spare a future child a life with a severe disorder (47%). The majority of survey respondents made an informed decision (86%), as assessed by the Multidimensional Measure of Informed Choice. Among the 86 respondents, 27 individual carriers and no new carrier couples were identified. Turn-around time of the test results was considered too long and costs were perceived as too high. Overall, mean levels of anxiety were not clinically elevated. High-risk respondents (n = 89) and pregnant respondents (n = 13) experienced higher levels of anxiety before testing, which decreased after receiving the test result. Although not clinically significant, distress was on average higher for carriers compared to non-carriers (p < 0.0001). All respondents would opt for the test again, and 80.2% would recommend it to others. The results suggest that ECS should ideally be offered before pregnancy, to minimise anxiety. This study could inform current and future implementation initiatives of preconception ECS.Subject terms: Genetic testing, Human behaviour     

Effect of Gelsemium 5CH and 15CH on anticipatory anxiety: a phase III, single-centre, randomized, placebo-controlled study

Therapeutics to treat or prevent anxiety are numerous but many people choose to try non‐conventional medicine such as homeopathy. This study aimed at evaluating the effectiveness of Gelsemium 5CH and 15CH on provoked anxiety in healthy volunteers, in comparison with placebo. This was a double‐blind, single‐centre, randomized, placebo‐controlled study. Eligible healthy men or women aged from 18 to 40 years without a history of psychiatric disorders were randomly allocated to receive Gelsemium 5 or 15CH or placebo. Anxiety was proved by performance of the Stroop colour word test (SCWT). The primary end‐point was anxiety assessed by the State measure of the State‐Trait Anxiety Inventory (STAI‐S) as the absolute value and difference with baseline, according to the treatment received. We included 180 healthy volunteers. The distribution into each treatment group was homogenous. There was no statistical difference between groups for the values of STAI‐S at baseline, just before the SCWT and the difference between these times (1.8 [0.20 to 3.4], 1.0 [?0.6 to 2.6] and 1.4 [?0.3 to 3.0] for Gelsemium 15CH, 5CH and placebo respectively). Likewise, no statistical difference was observed between groups in anxiety as measured by a Visual Analogue Scale and the Competitive State Anxiety Inventory. Mean arterial pressure and heart rate significantly increased (P < 0.001) but no interaction between time prior to provoked anxiety and treatment was shown (P = 0.59 and P = 0.46, respectively). Gelsemium 5CH and 15CH do not prevent anticipatory anxiety in the conditions used in this study.     

美洲远志根提取物对苯并芘致肺癌小鼠的抗肿瘤作用

目的：研究美洲远志（Polygala senega）根的乙醇提取物对苯并芘致肺癌小鼠的抗肿瘤作用。方法：瑞士白化小鼠被分为5组,每组6只。组1为对照组,予口服橄榄油;组2予苯并芘（50mg/kg体质量,溶于橄榄油中）,每周2次,连续4周;组3除予与组2相同的苯并芘外,再予48%乙醇;组4予与组2相同的苯并芘,并同时给予美洲远志的乙醇提取物,每日1次,连续16周;组5仅给予美洲远志的乙醇提取物,每日1次,连续16周。16周后,处死所有小鼠并检测和评价以下指标：2,2-二苯基-1-苦基肼（2,2-diphenyl-1-picrylhydrazyl,DPPH）法测定美洲远志乙醇提取物的抗氧化功效;分别称取各组小鼠的肺组织质量及体质量;彗星实验及酶联免疫吸附法检测DNA损伤情况;分别测定过氧化氢酶、超氧化物歧化酶、谷胱甘肽过氧化物酶、谷胱甘肽还原酶、脂质过氧化反应及总含硫化合物含量。结果：给予美洲远志乙醇提取物治疗的组4小鼠与组3模型组小鼠相比,体质量明显增加而肺组织质量明显降低（P〈0.01）。彗星实验结果显示组4小鼠的DNA损伤较组3小鼠明显减轻（P〈0.01）。酶联免疫吸附法测定p53蛋白水平,组4明显高于组3（P〈0.01）。组2和组3的模型小鼠与组1比较,脂质过氧化反应水平明显升高,而抗氧化标志物的水平明显降低（P〈0.05）,组4小鼠的这些指标被明显逆转（P〈0.01）。结论：美洲远志对于化学制剂致小鼠肺癌有明确的治疗效果。     

Anti-Cancer Effect of Moroccan Cobra Naja haje Venom and Its Fractions against Hepatocellular Carcinoma in 3D Cell Culture

Hepatocellular carcinoma (HCC) is the most common primary liver cancer in adults, the fifth most common malignancy worldwide and the third leading cause of cancer related death. An alternative to the surgical treatments and drugs, such as sorafenib, commonly used in medicine is necessary to overcome this public health problem. In this study, we determine the anticancer effect on HCC of Moroccan cobra Naja haje venom and its fraction obtained by gel filtration chromatography against Huh7.5 cancer cell line. Cells were grown together with WI38 human fibroblast cells, LX2 human hepatic stellate cell line, and human endothelial cells (HUVEC) in MCTS (multi-cellular tumor spheroids) models. The hepatotoxicity of venom and its fractions were also evaluated using the normal hepatocytes cell line (Fa2N-4 cells). Our results showed that an anti HCC activity of Moroccan cobra Naja haje venom and, more specifically, the F7 fraction of gel filtration chromatography exhibited the greatest anti-hepatocellular carcinoma effect by decreasing the size of MCTS. This effect is associated with a low toxicity against normal hepatocytes. These results strongly suggest that the F7 fraction of Moroccan cobra Naja haje venom obtained by gel filtration chromatography possesses the ability to inhibit cancer cells proliferation. More research is needed to identify the specific molecule(s) responsible for the anticancer effect and investigate their mechanism of action.     

Poly (lactide-co-glycolide) acid nanoencapsulation of a synthetic coumarin: cytotoxicity and bio-distribution in mice, in cancer cell line and interaction with calf thymus DNA as target

Several naturally occurring coumarin compounds, including scopoletin (7 hydroxy-6 methoxycoumarin), of plant origin have been reported to have anti-cancer potentials. A related but chemically synthesized coumarin, 4-methyl-7-hydroxy coumarin (SC), was also shown to have similar anti-cancer potentials. In the present study, to test if nano-encapsulated SC could be a more potent anti-cancer agent, we encapsulated SC with poly lactide-co-glycolide acid (PLGA) nanoparticles (Nano Coumarin; NC) and tested its potentials with a variety of protocols. NC demonstrated greater efficiency of drug uptake and showed anti-cancer potentials in melanoma cell line A375, as revealed from scanning electronic and atomic force microscopies. To test its possible interaction with target DNA, the combined data of circular dichroism spectra (CD) and melting temperature profile (T_m) of calf thymus DNA treated with NC were analyzed. Results indicated a concentration dependent interaction of NC with calf thymus DNA, bringing in effective change in structure and conformation, and forming a new complex that increased its stability. Particle size and morphology of NC determined through polydispersity index and zeta potential using dynamic light scattering qualified NC to be a more potent anti-cancer agent than SC. Further, SC and NC showed negligible cytotoxic effects on normal skin cells and peripheral blood mononuclear cells of mice. Distribution assay of PLGA nanoparticles in different tissues like brain, heart, kidneys, liver, lungs, and spleen in mice revealed the presence of nanoparticles in different tissues including brain, indicating that the particles could cross the blood brain barrier, significant information for drug design.     

Severe gestational hypertriglyceridemia: related complications and management

We present two cases of severe hypertriglyceridemia (HTG>10g/l) in pregnancy. The first reports the case of a primigravida with mild HTG before conception. Triglycerides (TG) increased thereafter (20.9g/l) during pregnancy causing pancreatitis and in utero fetal death at 24 weeks' gestation (WG). The second deals with the de novo occurrence of a severe HTG (19g/l) diagnosed incidentally at 34 WG and complicated by acute renal failure. Severe HTG in pregnancy threatens maternal and fetal prognosis. We have summarized the curative and preventive management of gravidic HTG.     

Prospective study of the changes in pharmacokinetics of immunosuppressive medications after laparoscopic sleeve gastrectomy

Laparoscopic sleeve gastrectomy induces weight loss via the creation of a restrictive gastric tube for early satiety and is associated with an accelerated gastric transit time. A prospective, single‐dose pharmacokinetic study was performed, prior to and after laparoscopic sleeve gastrectomy, for tacrolimus, extended‐release tacrolimus, mycophenolate mofetil, and enteric‐coated mycophenolate sodium. The study included 12 morbidly obese patients in chronic renal failure. The median decrease in body mass index was 8.8 kg/m² with an excess body weight loss of 54.9%. The AUC₂₄ of all drugs were increased after laparoscopic sleeve gastrectomy by 46%, 55%, 77%, and 74%, respectively. The maximum concentrations were increased for tacrolimus, extended‐release tacrolimus, and mycophenolate mofetil by 43%, 46%, and 65%. The apparent total clearances were decreased for tacrolimus, mycophenolate mofetil, and enteric‐coated mycophenolate sodium by 36%, 57%, and 38%. Laparoscopic sleeve gastrectomy can be associated with significant changes in pharmacokinetics of the drugs evaluated. The mechanism is likely decreased apparent drug clearance due to an increased drug exposure (from a more distal site of intestinal absorption with decreased intestinal metabolism), or decreased clearance (liver metabolism). Adapting the monitoring of immunosuppression will be important to avoid overdosing and potential side effects.