Deliberately infecting healthy volunteers with malaria parasites: Perceptions and experiences of participants and other stakeholders in a Kenyan-based malaria infection study

Controlled human malaria infection (CHMI) studies involve the deliberate infection of healthy volunteers with malaria parasites under controlled conditions to study immune responses and/or test drug or vaccine efficacy. An empirical ethics study was embedded in a CHMI study at a Kenyan research programme to explore stakeholders’ perceptions and experiences of deliberate infection and moral implications of these. Data for this qualitative study were collected through focus group discussions, in-depth interviews and non-participant observation. Sixty-nine participants were involved, including CHMI study volunteers, community representatives and research staff. Data were managed using QSR Nvivo 10 and analysed using an inductive-deductive approach, guided by ethics literature. CHMI volunteers had reasonable understanding of the study procedures. Decisions to join were influenced by study incentives, trust in the research institution, their assessment of associated burdens and motivation to support malaria vaccine development. However, deliberate malaria infection was a highly unusual research strategy for volunteers, community representatives and some study staff. Volunteers’ experiences of physical, emotional and social burdens or harms were often greater than anticipated initially, and fluctuated over time, related to specific procedures and events. Although unlikely to deter volunteers' participation in similar studies in furture, we argue that the dissonance between level of understanding of the burdens involved and actual experiences are morally relevant in relation to community engagement, informed consent processes, and ongoing support for volunteers and research staff. We further argue that ethics oversight of CHMI studies should take account of these issues in deciding whether consent, engagement and the balance of benefits and harms are reasonable in a given context.     

Limitations of Chromogranin A in clinical practice

Context: Usefulness of circulating Chromogranin A (CgA) for the diagnosis of neuroendocrine tumors (NEN) is controversial. The aim of the present study was to assess the actual role of this marker as diagnostic tool. Methods: Serum blood samples were obtained from 42 subjects affected with NEN, 120 subjects affected with non-endocrine neoplasias (non-NEN) and 100 non-neoplastic subjects affected with benign nodular goitre (NNG). Determination of CgA was performed by means of immunoradiometric assay. Results: The CgA levels among NEN-patients were not significantly different from NNG and non-NEN subjects. The Receiver operating characteristic (ROC) curves analysis failed to identify a feasible cut-off value for the differential diagnosis between NEN and the other conditions. Conclusion: Serum CgA is not helpful for the first-line diagnosis of NEN.     

Dual role of osteoblastic proenkephalin derived peptides in skeletal tissues

Proenkephalin encodes a group of small peptides with opiate-like activity, the endogenous opioids, known to function as neurohormones, neuromodulators, and neurotransmitters. Recently, we have demonstrated that in addition to its abundance in fetal brain tissue, proenkephalin is highly expressed in nondifferentiated mesodermal cells of developing fetuses. We identified the skeletal tissues, bone, and cartilage as major sites of proenkephalin expression. To examine the possibility that proenkephalin is involved in bone development we have studied the expression of this gene in bone-derived cells, its modulation by bone active hormones, and the effects of enkephalin-derived peptides on osteoblastic phenotype. Our studies revealed that osteoblastic cells synthesize high levels of proenkephalin mRNA which are translated, and the derived peptides are secreted. Reciprocal interrelationships between osteoblast maturation and proenkephalin expression were established. These results together with our observations demonstrating inhibitory effects of proenkephalin-derived peptides on osteoblastic alkaline phosphatase activity, strongly support the notion that proenkephalin is involved in bone development. A different direction of research by other investigators has established the capability of the opioid system in the periphery to participate in the control of pain. On the basis of these two lines of observation, we would like to present the following hypothesis: The potential of embryonic skeletal tissue to synthesize proenkephalin-derived peptides is retained in the adult in small defined undifferentiated cell populations. This potential is realized in certain situations requiring rapid growth, such as remodeling or fracture repair. We suggest that in these processes, similarly to the situation in the embryo, the undifferentiated dividing cells produce the endogenous opioids. In the adult these peptides may have a dual function, namely participating in the control of tissue regeneration and in the control of pain. © 1994 Wiley-Liss, Inc.     

Effect of root environment on proton efflux in wheat roots

Proton net efflux of wheat (Triticum aestivum L.) roots growing in sand culture or hydroponics was determined by measuring the pH values of the solution surrounding the roots by pH microelectrodes, by base titration and by color changes of a pH indicator in solid nutrient media. The proton net efflux was dependent on light, aeration, and source of nitrogen (NH ₄ ⁺ , NO ₃ ^? ). Ammonium ions caused the highest proton efflux, whereas nitrate ions decreased the proton efflux. Iron deficiency had no significant effect on proton efflux. Replacement of ammonium by nitrate inhibited proton efflux, whereas the reverse enhanced proton extrusion. A lag period between changes in plant environment and proton efflux was observed. The proton net efflux occurred at the basal portion of the roots but not in the root tips or at the elongation zone. Under optimal conditions, proton efflux capacity reached a maximum value of 5.7 μmole H⁺ g^?1 fresh weight h^?1 with an average (between different measurements) of 3.4 μmole H⁺ g^?1 fresh wth^?1 whereas the pH value decreased to 3.2–3.7 and reached a minimal value of 2.9. Inhibition of ATPase activity by orthovanadate inhibited proton efflux. The results indicate that proton efflux in wheat roots is ammonium ion and light dependent and probably governed by ATPase activity.     

Cytoplasm-enriched fragments ofChara: structure and electrophysiology

Summary Cytoplasm-enriched fragments prepared from internodal cells ofChara corallina by centrifugation contain membrane bound vesicles ranging in size from a few m to hundreds of m. If the fragments are incubated in artificial pond water (APW) of pH₀ above 6.5, neutral red stains the inside of many vesicles bright crimson, suggesting the presence of inward proton-pumping. In APW of pH₀ below 6 crimson vesicles are found less frequently. Under such conditions most vesicles remain unstained inside and some develop indistinct pink halos. After a few days most fragments form a central vacuole, which stains red, regardless of the pH₀. The cytoplasmic layer still contains vesicles after vacuole formation.In order to identify the membrane bounding the vesicles various fluorescent probes were applied either by injection into the fragment or directly onto the vesicles released into artificial cytoplasm. Lucifer yellow or 6 COOH-F move readily across the tonoplast in intact cells, but did not enter any vesicles. On the other hand, the fluorescent cationic stain DIOC, which is used to highlight mitochondria and especially endoplasmic reticulum, stained the vesicle membrane. Numerous elliptical or kidney shaped nuclei in the flowing cytoplasm were highlighted with DAPI. In some fragments the nuclei formed large agreggates sometimes filling the width of the fragment.Patch-clamping the vesicles in artificial cytoplasm showed the presence of several kinds of channels, some displaying similar behaviour to the K⁺ channels observed in cytoplasmic droplets.Analogous to the plasmalemma of intact cells, the fragments without vacuoles displayed electrophysiological states dominated by either K⁺ conduction, H⁺ (or OH^–) conduction or the proton pump. On the other hand, excitation transients in fragments were of low amplitude or absent altogether. Detailed comparisons of data from fragments and intact cells are shown. The effect of vacuole formation on fragment electrophysiology was also explored.     

Respiratory Na+ pump and Na+-dependent energetics inVibrio alginolyticus

The marine bacteriumVibrio alginolyticus was found to possess the respiratory Na⁺ pump that generates an electrochemical potential of Na⁺, which plays a central role in bioenergetics ofV. alginolyticus, as a direct result of respiration. Mutants defective in the Na⁺ pump revealed that one of the two kinds of NADH: quinone oxidoreductase requires Na⁺ for activity and functions as the Na⁺ pump. The Na⁺ pump composed of three subunits was purified and reconstituted into liposomes. Generation of membrane potential by the reconstituted proteoliposomes required Na⁺. The respiratory Na⁺ pump coupled to the NADH: quinone oxidoreductase was found in wide varieties of Gramnegative marine bacteria belonging to the generaAlcaligenes, Alteromonas, andVibrio, and showed a striking similarity in the mode of electron transfer and enzymic properties. Na⁺ extrusion seemed to be coupled to a dismutation reaction, which leads to the formation of quinol and quinone from semi-quinone radical.     

Behavioral responses of Diabrotica adults to plant-derived semiochemicals encapsulated in a starch borate matrix

The concept of encapsulating semiochemicals into a starch matrix is being studied for potential use in corn rootworm (CRW) management programs. During 1987, experiments were conducted to determine: 1) If volatile plant-derived Diabrotica spp. attractants could be encapsulated in a starch borate matrix (SBM), and 2) If various SBM-semiochemical formulations would attract Diabrotica species over time in field corn. Chemical analyses of fresh SBM formulations indicated that indole, estragole, veratrole, phenylacetaldehyde, and trans-anethole were not retained during formulation but trans-cinnamaldehyde, Beta-ionone, 1,2,4,-trimethoxybenzene, eugenol and isugenol were successfully encapsulated. Encapsulated semiochemical formulations were made into 20 mesh granules, placed in Pherocon ® 1C traps that were tied to corn plants, and sampled for CRW adults every 4 days from 11 July to 8 September. Field data indicated that encapsulated semiochemicals were retained in the SBM for varying lengths of time and were released at rates attractive to CRW adults. A two-component mixture of trans-cinnamaldehyde and 1,2,4-trimethoxybenzene was the most effective formulation tested; however, no formulation was effective during corn silking and pollination. Although seasonal variation in CRW response could limit the usefulness of some plant-derived semiochemicals, the starch matrix concept may be useful as a delivery system for semiochemicals and may have potential as a tool that could be used in the development of new more biorational CRW management programs.

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Résumé Le programme expérimental de 1987 était destiné à déterminer: 1) si les substances dérivées de végétaux et attractives pour Diabrotica pouvaient être encapsulées dans de l'amidon additionné d'acide borique; 2) si différentes formules attireraient les différentes espèces de Diabrotica dans un champ de maïs.L'indol, l'estragol, le vératrol, le phénylacétaldéhyde et le trans-anéthol n'ont pas été retenus, tandis que le trans-cinnamaldéhyde, la \-ionone, le 1,2,4-triméthobenzène, l'eugénol et l'isugénol ont été encapsulés avec succès dans des pièges attachés à des pieds de maïs (les détails techniques sont fournis). Les pièges ont été relevés tous les 4 jours du 11 juillet au 8 septembre. Les résultats montrent que les substances allélochimiques sont conservées dans la capsule pendant des durées variables et libérées à des concentrations attractives pour les Diabrotica adultes. Un mélange de trans-cinnamaldéhyde et de 1,2,4,-triméthoxybenzène a été la formule la plus efficace, à l'exception des périodes de formation des barbes et du pollen, où aucune formule n'a été attractive. Bien que la variation saisonnière des réactions de Diabrotica limite l'utilisation des substances allélochimiques d'origine végétale, la capsule d'amidon peut être employée pour libérer des substances allélochimiques et constitue un outil potentiel pour la mise au point d'une méthode plus rationnelle de lutte contre Diabrotica.

     

Prediction of temperature profiles in the human skin and subcutaneous tissues

Exact mathematical solutions in terms of confluent hypergeometric and Airy's functions are obtained to study the steady state temperature distributions in human skin and subcutaneous tissues (SST). It is assumed that the skin is exposed to an air environment and heat transfer from the skin occurs by convection, radiation and evaporation. A mathematical model of the SST, accounting for heat conduction, perfusion of the capillary beds and metabolic heat productions of the dermis and subcutaneous tissues, has been solved to obtain interface temperatures for a wide range of environmental temperatures, rates of evaporation of sweat, wind speeds and relative humidities. The solutions provide inter-relationships between interface temperatures, thermal conductivities, metabolic heat production, blood perfusion, thicknesses of various layers of SST and ambient temperature.     

左旋四氢巴马汀加强电针对兔大脑皮层牙髓诱发电位的抑制作用

家兔6只,用氨基甲酸乙酯和氯醛糖麻醉,电刺激牙髓,在对侧大脑皮层体感Ⅰ区引导其诱发电位,观察诱发电位各成分与痛的关系。结果观察到,在P1、N1、P2和 N2 4个波中,P1和 P2波相对稳定。其中,P2波(波峰潜伏期:66.1±1.9ms)具有较高的阈值,且不受无镇痛作用的中枢抑制剂安定的影响,而受小剂量镇痛剂度冷丁的抑制,提示 P2波与痛有关。以 P2波的波幅为指标,进一步在12只家兔上观察了 L-THP 和电针及两者合用对诱发电位的影响。结果显示,L-THP 和电针对诱发电位均有抑制作用,且两者在作用强度和时间上存在明显的协同,提示 L-THP 具有加强电针对兔大脑皮层牙髓诱发电位中痛相关成分的抑制作用。     

压脚痛阈测定法的改进和应用

本文介绍一种改进的压脚测痛法。采用电机驱动替代用手挤压橡皮球完成升压过程;通过一个自动的电路切断结构判定抽脚反应,较目视更加客观;用读数保持电路记录压力变化,较直接读取刻度值更加准确,可靠。这些优点,业经电针和吗啡镇痛实验验证。