Seasonal variation in the content of a febrifugine and isofebrifugine alkaloid mixture in aerial parts of <Emphasis Type="Italic">Hydrangea macrophylla</Emphasis> var. <Emphasis Type="Italic">Otaksa</Emphasis>, with special reference to its antimalarial activity

Febrifugine and isofebrifugine alkaloid mixtures extracted from the leaves and buds of Hydrangea macrophylla var. Otaksa, collected during different months, in Japan, were quantified using high-performance liquid chromatography. Leaves collected during the flowering season, namely from June to August, contained 0.16–0.31 mg/g of the alkaloid mixture, whereas those collected from September to December had less than 0.03 mg/g of the mixture. However, extracts of buds harvested from October to February contained a consistently larger amount (more than 0.49 mg/g) of the alkaloids. Hot-water extracts from the leaves and buds collected during different seasons were evaluated for antimalarial activity against Plasmodium yoelii 17XL in mice. The extract of leaves collected in August demonstrated high antimalarial activity, and all mice that received the extract survived the infection. In contrast, the extract of leaves collected in December showed little activity. The extract of buds collected in December cleared parasites, but with subsequent mortality to mouse. The present results show that the amount of antimalarial agent—febrifugine and isofebrifugine mixture—in H. macrophylla var. Otaksa is both part- and season-dependent, suggesting that the choice of plant parts and their harvesting season are important factors worth considering in the pharmacological use of medicinal plants.     

Effects of instruction by practice assistants on inhaler technique and respiratory symptoms of patients. A controlled randomized videotaped intervention study

BACKGROUND: Many patients with asthma or chronic obstructive pulmonary diseaseuse their medication inhalers incorrectly. General practitioners,pharmacists and other health care providers do not always havethe opportunity to instruct patients in correct inhaler technique. OBJECTIVE: To find out whether the inhaler technique and respiratory symptomsof patients can be improved after instruction by practice assistants. METHODS: Single blind, randomized intervention study in which 48 patientswho had been using a dry powder inhaler for at least one monthtook part. Their inhaler technique was videotaped on two visitswith a two-week interval between visits. The inhaler techniqueon the videos was subsequently scored by two experts on ninecriteria. At both visits the patients completed a questionnaireabout their respiratory symptoms. After the first video, 25patients were randomly chosen to receive instruction from oneof six practice assistants who had followed a one evening courseabout inhaler instruction, and who had been issued an instruction-set. RESULTS: The patients who received instruction had a significantly greaterreduction in number of mistakes at the second visit than thepatients who did not (P = 0.01). The instructed patients alsoreported less dyspnoea at the second visit (P = 0.03). No effectof instruction was found on wheezing, cough and sputum production. CONCLUSION: The inhaler technique of patients can be improved significantlyby the instruction of patients by trained practice assistants,possibly resulting in less dyspnoea. Keywords. Administration-inhalation, obstructive lung diseases, airways symptoms, patient-education, general practice.     

Molecular genetic characterization of XRCC4 function

XRCC4 is a generally expressed protein of 334 amino acids that is involved in the repair of DNA double-strand breaks and in V(D)J recombination, but its function is unknown. In this study, we have used a mutational approach and the yeast two-hybrid method to perform an initial characterization of this protein. We show that the XRCC4 protein is located in the nucleus. We also demonstrate that several potential phosphorylation sites are not required for XRCC4 function in a transient V(D)J recombination assay. In addition, we show that XRCC4 forms a homodimer in vivo with the homodimerization domain being located within amino acids 115-204. Finally, we define a core domain of XRCC4 that functions in V(D)J recombination and comprises amino acids 18-204. Potential functions of XRCC4 are discussed.      

Is fecundability associated with month of birth? An analysis of 19th and early 20th century family reconstitution data from The Netherlands

The relationship between fecundability and month of birth was investigated in a cohort of 1526 women who married between 1802 and 1929, using only women whose first marriage occurred before the age of 35 years. On the basis of their time to pregnancy (TTP, calculated as time between wedding and first birth minus gestational length), women were categorized into two groups: fecunds (TTP up to 12 months or prenuptial conceptions, n = 1348) and subfecunds (TTP >18 months, n = 118). By use of logistic regression, cosinor functions with a period of 1 year or 6 months and variable shift and amplitude were fitted through the monthly odds of subfecunds versus fecunds. The best fitting curve was unimodal, with a zenith in September (P = 0.13 for H0: no differences). Exclusion of childless women (n = 36, minimum follow-up 5 years) from the subfecunds led to a similar curve (P < 0.01), while childless women, as compared with fecunds, showed a birth distribution that was best represented with a bimodal curve with zeniths in January and July (P = 0.06). This study provides evidence for the existence of differences in fecundability by month of birth. The cause of this relationship is unclear, but may lie in a melatonin-dependent circannual variability of the quality of the oocyte.      

A randomized controlled trial testing the effectiveness of a universal school-based depression prevention program 'Op Volle Kracht' in the Netherlands

Background  

The incidence of depressive symptoms increases during adolescence, from 10.0% to 24.5% at age 11 to 15, respectively. Experiencing elevated levels of depressive symptoms increases the risk of a depressive disorder in adulthood. A universal school-based depression prevention program Op Volle Kracht (OVK) was developed, based on the Penn Resiliency Program, aimed at preventing the increase of depressive symptoms during adolescence and enhancing positive development. In this study the effectiveness of OVK will be tested and possible mediators of program effects will be focus of study as well.     

Factors that affect human hemopoiesis are produced by T-cell growth factor dependent and independent cultured T-cell leukemia-lymphoma cells

Some laboratory results and clinical situations suggest that human T cells may be important in the regulation of growth of hematopoietic cells. Since the discovery of T-cell growth factor (TCGF), systems are now available for the long-term specific in vitro propagation of mature normal or neoplastic human T cells, providing an opportunity to study the influence of T cells on hematopoiesis. Recently, 24 cell lines from patients with cutaneous T-cell lymphoma (CTCL) and T-cell acute lymphoblastic leukemia (T-ALL) were grown with TCGF and then assessed for release of humoral factors that affect hematopoiesis. Conditioned media (CM) from these cell lines were tested for erythroid burst- promoting activity (BPA) and granulocyte colony-stimulating activity (CSA). BPA was detected in CM from 3/6 cultures of T-ALL patients and 4/6 CTCL cultures. CSA was found in the CM from 6/8 cultures of T-ALL patients, 7/12 CTCL cultures, and 3/4 CTCL cell lines that become independent of exogenous TCGF for growth. The CSA from several of the neoplastic T-cell cultures stimulated high levels of eosinophil colonies, a possible source of the eosinophilia seen in these patients. The ability of continuously proliferating human T lymphocytes, which retain functional specificity and responsiveness to normal humoral regulation, to produce factors that directly or indirectly stimulate myeloid and erythroid colony formation lends further credence to the role of T lymphocytes in regulating hematopoiesis.     

Evaluation of erythropoiesis in long-term hamster bone marrow suspension cultures: absence of a requirement for adherent monolayer cells

In long-term hamster bone marrow cultures, proliferation and differentiation of hemopoietic stem cells occurs for several months without need for hydrocortisone or adherent stromal elements, which are requirements for bone marrow growth in all other species studied. Only the most primitive erythroid progenitors (BFU-E) are produced in the cultures. Following treatment of the cells with erythropoietin, these progenitor cells undergo differentiation into mature hemoglobinized red blood cells. Concomitant addition of erythropoietin (Epo) and prostaglandin-E1 (PGE1) results in the production of large numbers of maturing red blood cells. In cultures stimulated with Epo and PGE1, as many as 70% of the cells are benzidine-positive, while Epo alone stimulated as many as 45% of the cells to become erythroid. Epo and PGE1 do not have any apparent deleterious effect on the continuous hemopoiesis occurring in these cultures. Under identical conditions, syngeneic adherent cell cultures do not produce any erythroid elements. The development of mature red blood cells from primitive erythroid precursors occurs in the presence of Epo alone and without any apparent need for adherent stromal elements. These cultures provide a useful in vitro model for dissecting the positive and negative signals that regulate erythropoiesis.     

Transforming growth factor-beta trans-modulates the expression of colony stimulating factor receptors on murine hematopoietic progenitor cell lines

Transforming growth factor beta (TGF-beta) is a potent and selective growth inhibitor of early hematopoietic progenitors and leukemic cells. The cellular mechanism(s) underlying this antiproliferative effect is, however, currently unknown. In the present study, we demonstrate that TGF-beta inhibits the expression of granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin 3 (IL-3), and granulocyte-CSF (G-CSF) receptors on murine factor-dependent and independent hematopoietic progenitor cell lines without a significant change in receptor affinity. A maximum reduction in GM-CSF receptor numbers of 65% to 77% was observed by 96-hour incubation with TGF-beta. The TGF- beta induced trans-down-modulation of GM-CSF receptors was prolonged, noncytotoxic but reversible, and not due to endogenous production of GM- CSF. The TGF-beta induced reduction in CSF receptor numbers preceded TGF-beta's growth inhibitory action. In addition, the ED50 (1 to 10 pmol/L) for TGF-beta's CSF receptor modulatory and antiproliferative effect was similar. The effect of TGF-beta on cell surface CSF receptor expression was specific, because the expression of other cell surface proteins (Ly 5 and Ly 17) was not affected by TGF-beta treatment, and because other growth inhibitors (tumor necrosis factor and interferon) did not affect CSF receptor expression. These data suggest that the downregulation of the growth of hematopoietic progenitor cells by TGF- beta involves reducing the cell surface expression on growth factor receptors.     

An essential review of Singapore’s response to out-of-hospital cardiac arrests: improvements over a ten-year period

Care for patients who experience out-of-hospital cardiac arrest (OHCA) has rapidly evolved in the past decade. Increased sophistication of care in the community, emergency medical services (EMS) and hospital setting is associated with improved patient-centred outcomes. Notably, Utstein survival doubled from 11.6% to 23.1% between 2011 and 2016. These achievements involved collaboration between policymakers, clinicians and researchers, and were made possible by a strategic interplay of policy, research and implementation. We review the development and current state of OHCA in Singapore using primary population-based data from the Pan-Asian Resuscitation Outcomes Study and an unstructured search of research databases. We discuss the roles of important milestones in policy, community, dispatch, EMS and hospital interventions. Finally, we relate these interventions to relevant processes and outcomes, such as the relationship between the strategic implementation of bystander cardiopulmonary resuscitation and placement of automated external defibrillator with return of spontaneous circulation, survival to discharge and survival with favourable neurological outcomes.     

Anti-plasmodial activity of the extracts of some Kenyan medicinal plants

Ethnopharmacological relevance

The spread of drug resistant Plasmodium falciparum strains necessitates search for alternative newer drugs for use against malaria. Medicinal plants used traditionally in preparation of herbal medicines for malaria are potential source of new anti-malarial drugs.

Aim of the Study

To identify the anti-plasmodial potential of twelve plants used in preparing herbal remedies for malaria in Kilifi and Tharaka districts of Kenya.

Materials and Methods

Twelve plants used traditionally for anti-malarial therapy in Kilifi and Tharaka districts were extracted with water/methanol yielding twenty-three extracts. The extracts were tested against chloroquine sensitive (NF54) and resistant (ENT30) P. falciparum strains in vitro using ³Hypoxanthine assay.

Results

Seven (30%) extracts showed activity against P. falciparum with IC₅₀ values below 20 μg/ml. The remaining 16 extracts showed low or no activity. The most active extracts were from Zanthoxylum chalybeum (Rutaceae) with an IC₅₀ value of 3.65 μg/ml, Cyperus articulatus (Cyperaceae) with 4.84 μg/ml, and Cissampelos pareira (Menispermaceae) with 5.85 μg/ml.

Conclusions

This study revealed plants, that are potential sources of anti-malarial compounds. Anti-plasmodial activities of extracts of T. simplicifolia, C. pareira, and C. articulatus are reported for the first time.