Present and future studies on lipogenesis in animals and human subjects

Lipogenesis occurs in all vertebrate species and has a critical role in energy balance, providing a means whereby excess energy can be stored as a fat. The metabolic pathways involved and their tissue distribution in different species, including man, are well known. The responses of lipogenesis to diet and to physiological and pathological states have been the subject of many studies. At a molecular level the major rate-controlling enzymes have been identified and their acute, and to a lesser extent chronic, control by hormones have been investigated extensively. However, there is no reason to suppose that all factors regarding lipogenesis have been identified (e.g. the recent discovery of acylation-stimulating protein). Little is known about the movement of newly-synthesized triacylglycerols in cells, either for secretion or storage. The production of leptin and tumour necrosis factor alpha by adipocytes provides a novel means of feedback control of triacylglycerol production, leptin by decreasing appetite and tumour necrosis factor alpha by inducing insulin resistance. The synthesis of these peptides appears to vary with the amount of triacylglycerol in adipocytes, but the molecular basis of this process is unknown. Elucidation of the signalling systems involved in the acute and chronic regulation of lipogenesis is also important, both with respect to some homeorhetic adaptations and also in some pathological conditions (e.g. non-insulin-dependent diabetes). Finally, molecular biology is revealing unexpected complexities, such as multiple promoters and different isoforms of enzymes (e.g. acetyl-CoA carboxylase; EC 6.4.1.2) exhibiting tissue specificity. Molecular biology, through transgenesis, also offers novel and powerful means of manipulating lipogenesis.     

Real-time visual detection of Pi released by flagellar dynein ATPase

 Using a novel fluorescent probe for P_i, a method for the direct visualization of P_i release from reactivated flagellar dynein ATPase has been developed. The probe undergoes a fluorescence increase when it binds P_i. The technique involves simultaneous imaging of demembranated sperm tails by epi-fluorescence and dark-field microscopy, and the use of the caged ATP technique for axoneme reactivation. To limit diffusion and thus maintain the released P_i within the observed field of view, the assay is carried out within a minute droplet under oil (volume 5–15 pl). The video output of a recursively filtered ICCD camera is used to visualize the fluorescence signal, which is subsequently digitized and automatically analysed on a PC. A major advantage of this technique is that it enables simultaneous analysis of the ATP-utilization rate and the motility of the reactivated axonemes. Received: 24 November 1998 / Received after revision: 21 January 1999 / Accepted: 22 January 1999     

New non-cocaine-containing topical anesthetics compared with tetracaine-adrenaline-cocaine during repair of lacerations

OBJECTIVE: To compare the effectiveness of three new topical anesthetics that do not contain cocaine (prilocaine-phenylephrine, tetracaine-phenylephrine [tetraphen], and tetracaine-lidocaine-phenylephrine) to that of tetracaine-adrenaline-cocaine (TAC) during laceration repair in children. DESIGN: Prospective, randomized, double-blind clinical trial. SETTING: The emergency department of an urban children's hospital. PARTICIPANTS: Children 1 year of age or older with a laceration /= 5 years of age using a visual analogue scale (VAS). Suture technicians, research assistants, and parents also scored pain using a seven-point Likert scale. In addition, suture technicians completed an anesthetic effectiveness scale. RESULTS: There was consistently no difference demonstrated between the effectiveness of tetraphen and that of TAC for each outcome measure of each observer group. A statistically significant difference was seen among anesthetics when comparing VAS and Likert scale scores of suture technicians and Likert scale scores of research assistants. Based on post hoc analyses, these statistically significant differences were between TAC and prilocaine-phenylephrine (suture technician VAS and Likert scale) and between TAC and tetracaine-lidocaine-phenyl-ephrine (suture technician Likert scale), but not between TAC and tetraphen. When power analyses were performed using alpha = 0.05 and beta = 0.20, it was possible to detect a difference of 1.2 VAS units for each of the observer groups. Based on anesthetic effectiveness scale scores, the three new topical preparations collectively performed significantly better on the face and scalp than on the extremities (relative risk = 1.83; 95% confidence interval 1.20 < relative risk < 2.79). CONCLUSION: This study demonstrated the effectiveness and safety of three new non-cocaine-containing topical anesthetics. Consistently, there was no statistical difference demonstrated between the effectiveness of tetraphen and that of TAC for each outcome measure of each observer group. Tetraphen offers an effective alternative to TAC during laceration repair in children.     

Compulsory mourning

The bold decision was taken in Afghanistan in 2002 to provide donor-funded public health services by means of contracting-out of predefined health care packages. This study seeks to identify the extent to which progress has been made in public health services provision in the context of broader state-building agendas. The article argues that the provision of public health services was also intended to generate a peace dividend and to legitimize the newly established government. The widely portrayed success of the contracting model is backed up by very high official figures for health service coverage. This contrasts with evidence at household level, which suggests limited utilization of public health services, and perceptions that these offer inferior quality, and a preference for private providers. The dissonance between these findings is striking and confirms that public health care cannot remain immune from powerful market forces, nor from contextual determinants outside the health field.