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Biomedical subjects

C Pain

Publications and source records attributed to C Pain.

At least 19 recordsLinked to original sources
PubMed2006

Protection of normal human reconstructed epidermis from UV by catalase overexpression.

Reactive oxygen species (ROS) generated by ultraviolet (UV) irradiation are counterbalanced by endogenous antioxidant systems. To test the hypothesis of a novel photoprotective approach, we irradiated epidermis reconstructed with normal human keratinocytes overexpressing sustainably lentivirus-mediated catalase (CAT), copper/zinc superoxide dismutase (CuZnSOD) or manganese superoxide dismutase (MnSOD) enzymes. We found that following UVB irradiation there was a marked decrease in sunburn cell formation, caspase-3 activation and p53 accumulation in human reconstructed epidermis overexpressing CAT. Moreover, UVA-induced hypertrophy and DNA oxidation (8-oxodeoxyguanosine) were decreased by CAT overexpression. These effects were not achieved by overexpression of CuZnSOD or MnSOD. In conclusion, vector-mediated CAT overexpression could be a promising photoprotective tool against deleterious effects of UV irradiation such skin cancer especially in monogenic/polygenic photosensitive disorders characterized by ROS accumulation.

Apoptosis↗
PubMed2006

Skin ultrastructure in senile lentigo.

Senile lentigo is a common component of photoaged skin. It is characterized by hyperpigmented macules which affect chronically irradiated skin mostly after the age of 50. This study was undertaken to assess the morphology of senile lentigo on the dorsum of the hands. A systematic comparison between lesional and perilesional skin using histology and transmission electron microscopy was done to determine whether melanocytes or keratinocytes are affected in the evolution of lesions and which tissue structure is modified. The histology study showed that lesional skin is characterized by a hyperpigmented basal layer and an elongation of the rete ridges, which seem to drive deeply into the dermis. The epidermis contained clusters of keratinocytes, which retained and accumulated the melanin pigment. Electron microscopy studies showed important modifications in the lesional skin ultrastructure in comparison with perilesional skin. In melanocytes from perilesional and lesional skin, we observed normal size melanosomes at all stages of maturation in the cytoplasm and in migration within dendrites. No pigment accumulation was observed. However, the morphology of melanocytes in lesional skin revealed an activated status with numerous mitochondria and a well-developed endoplasmic reticulum, which could reflect intense protein synthesis. In basal keratinocytes from lesional skin, we observed numerous melanosome complexes called polymelanosomes, which formed massive caps on the nuclei. Observations in colored semi-thin sections also revealed perturbed structures in the basal layer region, which could explain the skin perturbation. Indeed, we observed keratinocytes that presented important microinvaginations and pendulum melanocytes, which sank into the dermis, beneath the basal layer of keratinocytes. These cell modifications seemed to be due to a perturbation of the dermal-epidermal junction, which appeared disorganized and disrupted and could directly disturb the basal support of the cells.

Aged↗
PubMed2005

A review of neuroimaging studies in PTSD: heterogeneity of response to symptom provocation.

Different experiential, psychophysiological, and neurobiological responses to traumatic symptom provocation in posttraumatic stress disorder (PTSD) have been reported in the literature. Two subtypes of trauma response have been hypothesized, one characterized predominantly by hyperarousal and the other primarily dissociative, each one representing unique pathways to chronic stress-related psychopathology. Recent PTSD neuroimaging findings in our own laboratory support this notion and are consistent with the view that grouping all PTSD subjects, regardless of their different symptom patterns, in the same diagnostic category may interfere with our understanding of posttrauma psychopathology. This review will integrate findings of different experiential, psychophysiological, and neurobiological responses to traumatic symptom provocation with the clinical symptomatology and the neurobiology of PTSD.

Brain↗
PubMed2003

Melanocyte detachment after skin friction in non lesional skin of patients with generalized vitiligo.

BACKGROUND: In vitiligo, melanocytes are gradually lost in depigmented macules of the skin. The disappearance of melanocytes has, however, not been clearly observed and consequently the aetiology of the disease (autoimmune, neural, cytotoxic) is still elusive. The starting point of vitiligo macules is frequently determined by local conditions such as wounds and excoriations, but may also follow minor traumas such as pressure or repeated friction. This prominent feature is often neglected. OBJECTIVES: To clarify the biological consequences of repeated friction on the attachment and survival of melanocytes in non lesional vitiligo skin. METHODS: Light reproducible skin friction was performed for 4 min on the volar forearm of 18 patients with extensive vitiligo and five controls with normal healthy skin. Biopsies from the test area and control skin were taken at 1, 4, 24 and 48 h following friction. Serial sections were examined with standard light microscopy, transmission electron microscopy, histochemistry and immunohistochemistry (dihydroxyphenylalanine, HMB-45, E-cadherin and an early apoptosis marker, M30 cytoDEATH antibody). RESULTS: The observation of sections at 1 and 48 h after friction on vitiligo skin and at all time points in controls revealed no changes. In contrast, in vitiligo skin at 4 and 24 h after friction, several melanocytes had undergone detachment and were found in various suprabasal positions, including the stratum spinosum, granular layer, and within and outside the stratum corneum. CONCLUSIONS: Detachment and transepidermal elimination of melanocytes following minor mechanical trauma in non lesional vitiligo skin is probably the cause of depigmentation occurring in the isomorphic response (Koebner phenomenon). We propose that transepidermal elimination of melanocytes in vitiligo should be regarded as a possible mechanism of chronic loss of pigment cells, perhaps previously damaged by another process.

Adult↗
PubMed2001

Maximising health gain within available resources in the New Zealand public health system.

OBJECTIVE: to obtain intervention-condition-specific investment and disinvestment recommendations which optimise the potential for health gain from existing respiratory diseases resource expenditure; and to trial a health economics technique for this purpose, assessing its usefulness as a means of prioritising health services resource allocation. DESIGN: a programme budgeting and marginal analysis (PBMA) exercise drawing upon the expertise of an advisory group of clinicians, managers and consumer advocates, supported by health authority staff. SETTING: the Southern and Midland health regions in New Zealand which have populations of one million and seven hundred thousand respectively. HEALTH SYSTEM CONTEXT: publicly funded secondary care sector in which regional health authority (RHA) purchasers contract for services with health care providers. METHODS: available evidence on the marginal costs and benefits of services for respiratory diseases was examined by an advisory group who produced investment and disinvestment recommendations by consensus using agreed prioritisation criteria. RESULTS: A list of specific investment and disinvestment proposals. Implementation plans for a number of investments formed part of the business plans for both RHAs in 1997/1998. No disinvestments were planned. CONCLUSIONS: prioritisation methods like PBMA, which are explicit and rational, can produce defensible evidence-based recommendations with the additional benefit of the credibility and support of an expert advisory group. The process encourages co-operative working and may itself have enduring benefits. However, preparation and conduct of such exercises is resource intensive and requires careful planning. This exercise has provided valuable lessons for the conduct of future prioritisation work.

Delivery of Health Care↗
PubMed2001

Using programme budgeting and marginal analysis to assist population based strategic planning for coronary heart disease.

OBJECTIVES: the objective of this project was to use programme budgeting and marginal analysis (PBMA), to inform the planning process of the South Western Sydney Area Health Service (SWSAHS) in respect of coronary heart disease (CHD). METHODS: a working party was established to carry out the project. The group set the parameters of the project and identified the programme, and associated the activity and resource use. Three sub-groups were established to undertake the marginal analysis. RESULTS: each sub-group (representing prevention, treatment, and rehabilitation for CHD) developed a list of potential strategies and provided estimates of resource use and consequences. These were prioritised and presented as recommendations to the SWSAHS. Some recommendations required enhancement funding for the SWSAHS. CONCLUSIOSN: while the use of PBMA presented some challenges, there were also some important outcomes. A comprehensive and detailed picture of resource use enabled the participants to form a view on how additional or reduced resources for CHD should be dealt with at the area level. The ultimate recommendations represent involvement by key stakeholders in the SWSAHS planning process, not just in identifying the 'vision' of CHD services, but also, how service delivery would be organised to achieve the overall objectives of reducing CHD morbidity and mortality.

Australia↗
PubMed2000

Studies on epidermis reconstructed with and without melanocytes: melanocytes prevent sunburn cell formation but not appearance of DNA damaged cells in fair-skinned caucasians.

To assess the photoprotective role of melanocytes in the epidermis, we studied the effects of ultraviolet B on an epidermis reconstructed with and without melanocytes. To address more specifically the role of melanin in fair-skinned individuals, experiments were done with cells obtained from human skin of low phototypes (II-III). To study the effect of constitutive melanin and possibly that of newly synthesized melanin precursors, a single dose of ultraviolet B (0.10 or 0.15 J per cm2, corresponding to a 4-5 minimal erythema dose in vivo) was administered to reconstructs and the effects were monitored over the first 24 h. When reconstructs with and without melanocytes were compared, no difference was found for DNA damage/repair assessed with antibodies to cyclobutane pyrimidine dimers and 6-4 photoproducts. More necrotic/apoptotic cells, however, were noted 24 h following ultraviolet B irradiation in reconstructs lacking melanocytes. Twenty-four hours following ultraviolet B irradiation the number of necrotic/apoptotic cells and the number of cyclobutane pyrimidine dimer positive cells was coarsely concentration-dependent. The number of cyclobutane pyrimidine dimer positive cells, however, was independent of the type of reconstruct used (with/without melanocytes). In conclusion, low phototype melanocytes seem to protect epidermal basal cells against ultraviolet B-induced apoptosis/necrosis and may preserve the overall integrity of the epidermis after ultraviolet B irradiation. On the contrary, such melanocytes do not seem to have a protective role against DNA damage and may not prevent cancer.

Adult↗
PubMed1999

An ex vivo study of congenital pigmented nevi in epidermal reconstructs.

In order to study morphologic and functional characteristics of pigment cells in congenital pigmented nevi, autologous or heterologous reconstructs have been made using normal keratinocytes and nevus cells from the dermal-epidermal junction or from the dermis. All these cells, keratinocytes and nevus cells, were used as cell suspensions immediately after dissociation from the tissues or after subsequent brief cultivation in a serum-free medium. Reconstructed epidermis were cultured for 15 days at the air-liquid interface with or without ultraviolet (UV) B exposure. The reconstructs were examined macroscopically (formation of hyperpigmented macules), histologically (pigment cell nesting) and ultrastructurally (pigment structure and transfer). Typical nesting of nevus cells was observed in the dermal-epidermal junction or in the superficial dermis associated with macroscopically detectable small pigmented macules. UVB exposure induced an upward migration of nevus cells in the suprabasal layers of the epidermis. This tissue model can be considered as an excellent system for the ex vivo reproduction of pigmented nevi and as an assay of the sensitivity of nevus cells towards UVB irradiation.

Cells, Cultured↗
PubMed1998

Chimeric human epidermal reconstructs to study the role of melanocytes and keratinocytes in pigmentation and photoprotection.

Chimeric epidermal reconstructs made with Negroid melanocytes and Caucasoid keratinocytes (or vice versa) were studied before and after UVB irradiation to understand the respective roles of these cells in tanning and photoprotection, especially lipoperoxidation and enzymatic defences against free radicals. Using this approach, we have confirmed overall the theory of the epidermal melanin unit. We have also shown that melanocytes of poorly tanning Caucasoids, which have a comparatively higher content of unsaturated fatty acids in their cell membrane, are more prone to the peroxidative effects of UV light, and that keratinocytes participate in photoprotection via phototype-dependent antioxidant enzyme activities, especially for catalase.

Adult↗
PubMed1997

Use of human skin reconstructs in the study of pigment modifiers.

OBJECTIVE: To assay drugs that modify pigmentation (ie, agents that either enhance or decrease pigmentation) in a predictive in vitro model, as such drugs have been previously studied in vivo on human and animal skin. DESIGN: An epidermis was reconstructed with human keratinocytes and melanocytes. Epidermal reconstructs with melanocytes were made according to a variant of the model of Pruniéras and colleagues. Reagents that alter melanogenesis such as isobutyl methylxanthine, 1-oleoyl-2-acetyl-sn-glycerol, kojic acid, and mequinol were introduced in the culture medium or used topically after 8 days of culture at the air-liquid interface. MAIN OUTCOME MEASURES: Macroscopic, colorimetric, histological (Fontana-Masson stain and dopa reaction), and biochemical studies were performed. RESULTS: The effect of pigment modifiers was demonstrated ex vivo as expected from in vivo data on skin color, numbers of melanocytes, melanosome transfer, and melanin content. CONCLUSION: These results will permit other investigators to use this model to assess the efficacy of novel molecules that alter pigmentation.

1-Methyl-3-isobutylxanthine↗
PubMed1997

Epidermal reconstructs in vitiligo: an extrinsic factor is needed to trigger the disease.

The primary cellular or molecular targets accounting for melanocytes loss in vitiligo are not clearly identified. To study a putative latent epidermal defect in the epidermis of vitiligo patients, we performed in vitro studies using cultured vitiligo melanocytes and keratinocytes transplanted on to a dead de-epidermized dermis according to a variant of Pruniéras' technique. Control autologous constructs were made with keratinocytes and melanocytes of normal adult epidermis and vitiligo epidermis from perilesional skin. For heterologous reconstructs we combined vitiligo-derived melanocytes or keratinocytes with their normal phototype-matched counterpart. After 15 days of culture at the air-liquid interface, epidermal reconstructs were studied macroscopically and microscopically. Immunohistochemistry was performed using antibodies to TRP-1 and NKI-beteb. All heterologous and autologous reconstructs made with melanocytes and keratinocytes from vitiligo patients had a normal histology and ultrastructure. For vitiligo melanocytes or normal melanocytes submitted to the influence of vitiligo keratinocytes, immunophenotype and function (pigment production and transfer) were similar to normal controls. So, without additional noxious stimuli, we could not discriminate between melanocytes and keratinocytes as inducers of the disease. Our data suggest that the basic abnormality in vitiligo vulgaris needs extrinsic factors to be macroscopically revealed or requires a longer period of culture to develop. Our model will allow analysis of the various pathophysiological mechanisms of vitiligo, e.g. autoantibodies or oxidative stress, at the cellular, biochemical or molecular level.

Adult↗
PubMed1996

Ex vivo study of skin phototypes.

We studied skin phototypes ex vivo to validate a model of epidermal reconstruction with melanocytes. We made autologous epidermal reconstructs with keratinocytes and melanocytes of healthy donors of skin phototypes I to VI. Keratinocytes and melanocytes were seeded on a dead de-epidermized dermis (Pruniéras type) at a 1:20 melanocyte/keratinocyte ratio. Reconstructed epidermis was grown for 15 d at the air-liquid interface with or without ultraviolet B irradiation. A macroscopic, chromometric. histologic, and ultrastructural evaluation was performed. Reconstructs reproduced the initial phototype with few modifications. The intensity of melanin transfer correlated with the in vivo situation and was stimulated after ultraviolet B irradiation in reconstructs of all categories of skin phototypes.

Adult↗
PubMed1995

Measurement by the polymerase chain reaction of the Epstein-Barr virus load in infectious mononucleosis and AIDS-related non-Hodgkin's lymphomas.

A polymerase chain reaction (PCR) assay for the detection of Epstein-Barr virus (EBV) sequences in various clinical samples, especially peripheral blood leukocytes (PBL) and serum, was carried out and the results obtained were compared with specific EBV serology. One hundred seventy patients were enrolled in the study: 89 healthy blood donors, 22 asymptomatic patients, 36 individuals with primary EBV infection (including 19 patients with infectious mononucleosis [IM]), 22 HIV-infected subjects (including 4 with hairy oral leukoplakia, 3 with central nervous disorders, and 15 with non-Hodgkin's lymphoma). All the serum samples from the healthy blood donors were negative. In patients with IM and in AIDS-non Hodgkin's lymphoma (ARNHL), PCR was strongly positive in leukocytes (> 2,000 genome equivalents/10(4) cells), which was correlated with detectable amounts of EBV DNA in serum. The overall positivity rate of PCR in serum was 58.8%, 68%, and 73% of cases for non-IM primary EBV infections, IM, and ARNHL, respectively. In two cases of EBV primary infection, the viral DNA was detected in serum, respectively 1 month and 2 months before IgM positivity and IgG rise. In one case of ARNHL followed up for several months, PCR (viral load of 2,000 genome equivalents/10(4) cells) became positive concurrently with appearance of lymphoma. In immunocompromised individuals, PCR EBV, if carried out in larger prospective studies, could be considered as a tumor marker, useful for predicting EBV-driven lymphoma and follow-up therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Tolerance to the hypothermic but not to the analgesic effect of [D-Trp11]neurotensin during the semichronic intracerebroventricular infusion of the peptide in rats.

The peptidase-resistant derivative of neurotensin, [D-Trp11]neurotensin, has been continuously infused intracerebroventricularly (75 ng/h) with an osmotic minipump for 10 days. On several days during this infusion the locomotor activity, the body temperature, the food intake, the body weight, and the nociceptive response in the plantar test were measured. A nonsignificant decrease of body temperature and a sustained analgesic effect were observed at each time considered. The response to a test dose of [D-Trp11]neurotensin (75 ng per rat) injected intracerebroventricularly at the 10th day of the chronic infusion revealed a complete tolerance to its hypothermic effect. Thus, it appears that the analgesic effect of [D-Trp11]neurotensin is independent of a hypothermic or an incapacitating effect of the peptide and does not give rise to tolerance after a 10-day continuous administration, in contrast to the hypothermic effect.

Analgesics↗