Corrigendum to "Antiproliferative and Apoptosis Induction Potential of the Methanolic Leaf Extract of Holarrhena floribunda (G. Don)".

[This corrects the article DOI: 10.1155/2015/756482.].

Cytotoxic and cell cycle arrest properties of two steroidal alkaloids isolated from Holarrhena floribunda (G. Don) T. Durand & Schinz leaves.

BACKGROUND: The plant Holarrhena floribunda (H. floribunda; G. Don) is indigenous to sub-Saharan Africa and is traditionally used to treat several ailments. The present study was carried out to isolate and characterize bioactive compounds with anti-proliferative activity present in H. floribunda extracts. METHODS: Compounds were isolated from H. floribunda using the bioassay-guided fractionation technique of repeated column chromatography and the step-wise application of the MTT reduction assay to assess antiproliferative bioactivity. The structures of the compounds were identified mainly using NMR. The effects of the isolated compounds on the viability, cell cycle and proliferation of human cancer cell lines (MCF-7, HeLa and HT-29) as well as the non-cancerous human fibroblast cell line (KMST-6) were investigated. RESULTS: Bioassay-guided fractionation yielded two steroidal alkaloids: holamine (1) and funtumine (2). The MTT reduction assay shows that both compounds exhibited selective dose-dependent cytotoxicity against the cancer cell lines studied. The isolated compounds induced cell cycle arrest at the G0/G1 and G2/M phases in the cancer cell lines with significant reduction in DNA synthesis. The results obtained show that the cancer cells (MCF-7, HeLa and HT-29) used in this study were more sensitive to the isolated compounds compared to the noncancerous fibroblast cells (KMST-6). CONCLUSION: The ability of the isolated compounds to cause cell cycle arrest and reduce DNA synthesis raises hopes for their possible development and use as potent anticancer drugs. However, more mechanistic studies need to be done for complete validation of the efficacy of the two compounds.

Antiproliferative and Apoptosis Induction Potential of the Methanolic Leaf Extract of Holarrhena floribunda (G. Don).

Natural plant products with potent growth inhibition and apoptosis induction properties are extensively being investigated for their cancer chemopreventive potential. Holarrhena floribunda (HF) is used in a wide range of traditional medicine practices. The present study investigated the antiproliferative and apoptosis induction potential of methanolic leaf extracts of HF against breast (MCF-7), colorectal (HT-29), and cervical (HeLa) cancer cells relative to normal KMST-6 fibroblasts. The MTT assay in conjunction with the trypan blue dye exclusion and clonogenic assays were used to determine the effects of the extracts on the cells. Caspase activities were assayed with Caspase-Glo 3/7 and Caspase-9 kits. Apoptosis induction was monitored by flow cytometry using the APOPercentage and Annexin V-FITC kits. Reactive oxygen species (ROS) was measured using the fluorogenic molecular probe 5-(and-6)-chloromethyl-2',7'-dichlorofluorescein diacetate acetyl ester and cell cycle arrest was detected with propidium iodide. Dose-response analyses of the extract showed greater sensitivity in cancer cell lines than in fibroblast controls. Induction of apoptosis, ROS, and cell cycle arrest were time- and dose-dependent for the cancer cell lines studied. These findings provide a basis for further studies on the isolation, characterization, and mechanistic evaluation of the bioactive compounds responsible for the antiproliferative activity of the plant extract.

Midwives' experiences of managing women in labour in the Limpopo Province of South Africa.

INTRODUCTION: The objective of this study was to explore and describe the experiences of midwives managing women during labour at a tertiary care hospital in the Limpopo Province. An exploratory, descriptive, contextual and inductive design was applied to this qualitative research study. Purposive sampling was used to select midwives who were working in the childbirth unit and had managed women during labour. A sample of 12 midwives participated in this study. Data were collected by means of unstructured individual interviews and analysed through an open coding method by the researchers and the independent co-coder. FINDINGS: Categories identified were lack of mutual participation and responsibility sharing, dependency and lack of decision-making, lack of information-sharing, empowering autonomy and informed choices opportunities, lack of open communication and listening, non-accommodative midwifery actions, and lack of human and material infrastructure. To ensure the validity of the results, criteria to measure trustworthiness were utilized. CONCLUSIONS: This study has implications for woman-centered care by midwives managing women in labour and provides appropriate guidelines that should be integrated into the Batho-Pele Principles.

Midwives' Experiences of Managing Women in Labour in the Limpopo Province of South Africa

Introduction:The objective of this study was to explore and describe the experiences of midwives managing women during labour at a tertiary care hospital in the Limpopo Province. An exploratory; descriptive; contextual and inductive design was applied to this qualitative research study. Purposive sampling was used to select midwives who were working in the childbirth unit and had managed women during labour. A sample of 12 midwives participated in this study. Data were collected by means of unstructured individual interviews and analysed through an open coding method by the researchers and the independent co-coder. Findings: Categories identified were lack of mutual participation and responsibility sharing; dependency and lack of decision-making; lack of information-sharing; empowering autonomy and informed choices opportunities; lack of open communication and listening; non-accommodative midwifery actions; and lack of human and material infrastructure. To ensure the validity of the results; criteria to measure trustworthiness were utilized. Conclusions: This study has implications for woman-centered care by midwives managing women in labour and provides appropriate guidelines that should be integrated into the Batho-Pele Principles

The ratio of serum transferrin receptor and serum ferritin in the diagnosis of iron status.

Laboratory tests used in the diagnosis of iron status lack specificity in defining iron deficiency anaemia (IDA) and anaemia of inflammation (AI). The serum transferrin receptor (sTfR) may provide more information in this regard. The iron status of 561 pre-school children was determined and classified using the conventional measurements. The value of the concentration of sTfR, the ratio of sTfR (microg/ml) to LogSF (microg/l) (TfR-Index), and the Log of the ratio of sTfR (microg/l) to SF (microg/l)--(LogTfR:Fer ratio), in the classification of the iron status were determined by comparing their distributions across the classification of iron status. Although there were significant differences in sTfR and TfR-Index across the categories of iron status, there was considerable overlap. All subjects with iron deficiency had LogTfR:Fer ratio > 2.55, whereas in all subjects classified as AI it was < 2.55, thus clearly separating the two. The LogTfR:Fer ratio was not able to exclude IDA in the presence of inflammation. However, in cases of combined IDA and AI the LogTfR:Fer ratio was < 2.55 but increased to > 2.55 after resolution of the inflammation. This novel method of calculating the LogTfR:Fer ratio may provide a more precise classification of the iron status of children.

Tunicamycin potentiates drug cytotoxicity and vincristine retention in multidrug resistant cell lines.

Tunicamycin (TM), an inhibitor of glycoprotein processing, was investigated for its potential to reverse the multiple drug resistance (MDR) phenotype. When TM was added in vitro to drug-resistant NIH-3T3-MDR and KB-8-5-11 cells, they developed an increased sensitivity to doxorubicin, epirubicin, vincristine and colchicine. Similarly, the sensitivity of NIH-3T3-MDR cells to cisplatin was also enhanced by TM. In the presence of TM, drug-sensitive NIH-3T3-parental cells exhibited greater susceptibility to the toxic effects of doxorubicin, epirubicin, vincristine (marginally significant), and colchicine, but not to cisplatin. Tunicamycin-treated drug-sensitive KB-3-1 cells showed an increased response to vincristine, but not to the other anticancer drugs. Pretreatment with TM inhibited glycoprotein synthesis in all the cell lines. Neither prior exposure to, nor co-incubation with TM, influenced the uptake of vincristine (VCR) in the various cell lines. However, NIH-3T3-MDR cells accumulated less VCR than their drug-sensitive controls and also exhibited reduced efflux of the drug when treated with TM. There were no significant differences in the levels of intracellular VCR uptake between drug-sensitive KB-3-1 and KB-8-5-11 cells. Tunicamycin increased intracellular VCR retention in KB-8-5-11 and NIH-3T3-MDR cells, but not in NIH-3T3-parental cells. However, drug-sensitive KB-3-1 cells expressed reduced VCR retention in response to TM exposure, indicating that correlations between VCR toxicity and its retention in the presence of TM should be made with caution. The results suggest that the enhancement of intracellular VCR retention in MDR cells lines caused by TM is likely to be the result of inhibition of VCR efflux. Inhibition of glycoprotein synthesis during TM exposure may account for the changes in VCR efflux and retention observed in the MDR cell lines. The enhancement of cisplatin cytotoxicity in NIH-3T3-MDR cells after exposure to TM is an interesting observation, since it is generally believed that agents which modify the MDR phenotype do not show a sensitising effect to cisplatin. These findings may have applications in the reversal of drug resistance.

Disulfide-bonded heparan sulfate proteoglycans associated with the surfaces of cultured bovine vascular endothelial cells.

A predominant species of heparan sulfate proteoglycan that consisted of at least two subunits linked by disulfide bonding was isolated from cell layers of normal ('cobblestone') bovine vascular endothelial cells in culture. Treatment of the parent molecules with dithiothreitol caused their complete cleavage and permitted the subsequent separation of the larger and smaller subunits on Sepharose CL-4B columns. Removal of dithiothreitol by dialysis resulted in the reformation of large disulfide-bonded molecules but such recombination of the subunits was prevented by prior reductive alkylation using iodoacetamide. Buoyant density gradient analysis as well as gel chromatography on Sepharose CL-6B columns, following alkaline borohydride and nitrous acid treatment of individual carbohydrate-rich subunits, showed that the latter consisted of core proteins associated solely with heparan sulfate glycosaminoglycans. The sizes of the latter were estimated by chromatographic techniques to be approximately 50 kDa in the case of the larger and 14 kDa for the smaller subunit. This is the first description of disulfide-bonded proteoheparan sulfates in endothelial cells.

Post natal side effects in rats induced by hypolipidaemic treatment during pregnancy.

Maternal, foetal and peri- and post-natal toxicity studies of a hypolipidaemic agent, 2-[p-(2,2-dichlorocyclopropyl)phenoxy]-2-methyl propionic acid (WIN 35833), were performed on different animal species during animal evaluation of this new drug. In teratology studies in rats, mice and rabbits, no adverse effects were detected following drug exposure during the organogenesis period. In peri-natal studies, a neonatal abnormality related to treatment just before term was shown in rats. This modification, previously observed with other hypolipidaemic drugs, seems to be species specific and characteristic of compounds in the aryloxyalkanoic acid series.

Effects of prenatal administration of acetylsalicylic acid in rats.

Acetylsalicylic acid (ASA) administration (200 mg/kg/day) during the last six days of pregnancy in the rat has been observed to result in: (a) a prolongation of the duration of pregnancy; (b) a prolongation of the parturition time; (c) the appearance, in some individuals, of dystocia with possible secondary death of foetuses in utero.