Report of the Vaccine Damage Steering Group

Report of the Vaccine Damage Steering Group Click here to download PDF 1.1mb

You don't have to be drunk to be doing real damage

This booklet highlights the effects of binge drinking ie packing drinking into a few sessions, usually at the weekend.

Melanopsin as a sleep modulator: circadian gating of the direct effects of light on sleep and altered sleep homeostasis in Opn4(-/-) mice.

Light influences sleep and alertness either indirectly through a well-characterized circadian pathway or directly through yet poorly understood mechanisms. Melanopsin (Opn4) is a retinal photopigment crucial for conveying nonvisual light information to the brain. Through extensive characterization of sleep and the electrocorticogram (ECoG) in melanopsin-deficient (Opn4(-/-)) mice under various light-dark (LD) schedules, we assessed the role of melanopsin in mediating the effects of light on sleep and ECoG activity. In control mice, a light pulse given during the habitual dark period readily induced sleep, whereas a dark pulse given during the habitual light period induced waking with pronounced theta (7-10 Hz) and gamma (40-70 Hz) activity, the ECoG correlates of alertness. In contrast, light failed to induce sleep in Opn4(-/-) mice, and the dark-pulse-induced increase in theta and gamma activity was delayed. A 24-h recording under a LD 1-hratio1-h schedule revealed that the failure to respond to light in Opn4(-/-) mice was restricted to the subjective dark period. Light induced c-Fos immunoreactivity in the suprachiasmatic nuclei (SCN) and in sleep-active ventrolateral preoptic (VLPO) neurons was importantly reduced in Opn4(-/-) mice, implicating both sleep-regulatory structures in the melanopsin-mediated effects of light. In addition to these acute light effects, Opn4(-/-) mice slept 1 h less during the 12-h light period of a LD 12ratio12 schedule owing to a lengthening of waking bouts. Despite this reduction in sleep time, ECoG delta power, a marker of sleep need, was decreased in Opn4(-/-) mice for most of the (subjective) dark period. Delta power reached after a 6-h sleep deprivation was similarly reduced in Opn4(-/-) mice. In mice, melanopsin's contribution to the direct effects of light on sleep is limited to the dark or active period, suggesting that at this circadian phase, melanopsin compensates for circadian variations in the photo sensitivity of other light-encoding pathways such as rod and cones. Our study, furthermore, demonstrates that lack of melanopsin alters sleep homeostasis. These findings call for a reevaluation of the role of light on mammalian physiology and behavior.

Every cigarette is doing you damage

This leaflet explains the dangers of smoking and why you should stop. It also provides information on nicotine replacement therapy (NRT) and non-nicotine treatments as well as other sources of help and advice.

You don't have to be drunk to be doing real damage

This poster highlights that binge drinking is dangerous, even if you don't get drunk.

Ecstasy can cause brain damage

This poster informs about the dangers of Ecstasy stating: 'Medical research proves that Ecstasy can cause brain damage. Deny it all you like, but you know it won't wash'.

Eye screening for diabetics - prevents blindness

Diabetes is a common condition affecting around 69,000 people in Northern Ireland. One of the possible complications of diabetes is a condition called diabetic retinopathy, which can cause sight loss and blindness. Retinopathy causes damage to the tiny blood vessels (capillaries) that nourish the retina, the tissues in the back of the eye that deal with light. This can seriously affect vision.Research shows that if retinopathy is identified early, for example through retinal screening, and treated appropriately, blindness can be prevented in the majority of people with diabetes, both type 1 and type 2.Screening programmeIn Northern Ireland, a diabetic retinopathy screening programme (DRSP), run by the Public Health Agency, has been put in place to screen all eligible people with diabetes aged 12 years and over. Dr Bernadette Cullen, Consultant in Public Health Medicine, PHA, said: "Screening detects problems early and allows appropriate treatment to be offered. It is vital that everyone with diabetes attends diabetic retinopathy screening when it is offered. Early detection of potential problems offers a very real opportunity to intervene and, with appropriate treatment, can prevent blindness in the majority of those at risk."The screening testThe screening test involves photographs being taken of the back of each eye, using a special camera. The test is painless and takes about 15 minutes. If the person is over 50 years of age, they will need to have drops put in their eyes about 15 minutes before the test to dilate their pupils.The photographs are sent to the regional screening centre for analysis by trained graders. Results will show whether patients require further referral for assessment or treatment by hospital eye services (HES). If this is not required, screening will be offered again the following year.GPs are informed of all results and if the patient is under the care of a diabetologist, they too will be informed. Patients are informed of results by their GP and if they need an urgent referral, protocols are in place to ensure this happens.Many people with diabetes attend their optometrist (optician) on a regular basis to have a sight test for glasses. It is important they continue to do this - this test is free to people with diabetes. It is also vital that people with diabetes attend for diabetic retinopathy screening when invited, regardless of how or where their diabetes is treated, or whether they visit a hospital consultant/GP for their diabetic care.Patients are invited to screening via their GP practice. An information leaflet to help patients make an informed decision to attend for screening is also sent. This can be accessed via the PHA website: www.publichealth.hscni.net.

Histopathological and ultrastructural effects of delta-endotoxins of Bacillus thuringiensis serovar israelensis in the midgut of Simulium pertinax larvae (Diptera, Simuliidae)

The bacterium Bacillus thuringiensis (Bt) produces parasporal crystals containing delta-endotoxins responsible for selective insecticidal activity on larvae. Upon ingestion, these crystals are solubilized in the midgut lumen and converted into active toxins that bind to receptors present on the microvilli causing serious damage to the epithelial columnar cells. We investigated the effect of these endotoxins on larvae of the Simulium pertinax, a common black fly in Brazil, using several concentrations during 4 h of the serovar israelensis strain IPS-82 (LFB-FIOCRUZ 584), serotype H-14 type strain of the Institute Pasteur, Paris. Light and electron microscope observations revealed, by time and endotoxin concentration, increasing damages of the larvae midgut epithelium. The most characteristic effects were midgut columnar cell vacuolization, microvilli damages, epithelium cell contents passing into the midgut lumen and finally the cell death. This article is the first report of the histopathological effects of the Bti endotoxins in the midgut of S. pertinax larvae and the data obtained may contribute to a better understanding of the mode of action of this bacterial strain used as bioinsecticide against black fly larvae.

A pea plasma membrane protein exhibiting blue light-induced phosphorylation retains photosensitivity following triton solubilization.

Phosphorylation of a polypeptide of approximately 120 kD in pea (Pisum sativum L.) plasma membranes in response to blue light has been shown to be involved in phototropic curvature, but the relationship of this protein to the kinase and photoreceptor acting upon it is uncertain. Using two-phase aqueous partitioning to isolate right-side-out plasma membrane vesicles, we have obtained evidence suggesting that the photoreceptor, kinase, and substrate are localized to the plasma membrane fraction. Latent phosphorylation accessible through Triton X-100 or freeze/thaw treatments of purified plasma membrane vesicles indicates that at least the kinase moiety is present on the internal face of the plasma membrane. Effects of solubilization of vesicles on fluence-response characteristics and on phosphorylation levels provide evidence that the receptor, kinase, and protein substrate are present together in individual mixed detergent micelles, either as a stable complex or as domains of a single polypeptide. In vivo blue-light irradiation results in a small but significant decrease in mobility of the 120-kD phosphorylated protein on sodium dodecylsulfate gel electrophoresis. This mobility shift is evident on Coomassie-stained gels and on western blots probed with polyclonal antibodies raised against the 120-kD protein. Among the plasma membrane proteins bound to the reactive nucleotide analog fluorosulfonylbenzoyladenine (FSBA), a distinct protein band at 120 kD can be detected on blots probed with anti-FSBA antibodies. This band exhibits an in vivo light-dependent mobility shift identical to that observed for the protein band and antibodies specific for the 120-kD protein, implying that the 120-kD protein has an integral nucleotide binding site and consistent with the possibility that the substrate protein is also a kinase.

Light receptor action is critical for maintaining plant biomass at warm ambient temperatures.

The ability to withstand environmental temperature variation is essential for plant survival. Former studies in Arabidopsis revealed that light signalling pathways had a potentially unique role in shielding plant growth and development from seasonal and daily fluctuations in temperature. In this paper we describe the molecular circuitry through which the light receptors cry1 and phyB buffer the impact of warm ambient temperatures. We show that the light signalling component HFR1 acts to minimise the potentially devastating effects of elevated temperature on plant physiology. Light is known to stabilise levels of HFR1 protein by suppressing proteasome-mediated destruction of HFR1. We demonstrate that light-dependent accumulation and activity of HFR1 are highly temperature dependent. The increased potency of HFR1 at warmer temperatures provides an important restraint on PIF4 that drives elongation growth. We show that warm ambient temperatures promote the accumulation of phosphorylated PIF4. However, repression of PIF4 activity by phyB and cry1 (via HFR1) is critical for controlling growth and maintaining physiology as temperatures rise. Loss of this light-mediated restraint has severe consequences for adult plants which have greatly reduced biomass.

Every cigarette is doing your baby damage

This poster highlights the fact that smoking while pregnant increases the risk of low birth weight, premature birth, stillbirth and cot death, and directs women to the Smokers' Helpline.

Every cigarette is doing you damage

This poster was produced as part of the PHA's public information campaign on smoking.

Characterization of the gene expression related to the process of DNA damage tolerance in Schistosoma mansoni

In the course of its complex life cycle, the parasite Schistosoma mansoni need to adapt to distinct environments, and consequently is exposed to various DNA damaging agents. The Schistosoma genome sequencing initiative has uncovered sequences from genes and transcripts related to the process of DNA damage tolerance as the enzymes UBC13, MMS2, and RAD6. In the present work, we evaluate the importance of this process in different stages of the life cycle of this parasite. The importance is evidenced by expression and phylogenetic profiles, which show the conservation of this pathway from protozoa to mammalians on evolution.