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Biomedical subjects

M Nicol

Publications and source records attributed to M Nicol.

At least 37 records · Page 2Linked to original sources
PubMed1996

Modulation of ultraviolet light-induced oxidative stress in mice skin related to dietary vitamin A and selenium intake.

Weanling female SKH1 hairless mice were randomly divided into 4 groups. Each group was fed a particular regimen for 20 weeks: 1) normal basal diet with 5 IU vitamin A/g and 0.45 microgram selenium/g, 2) vitamin A deficient, 3) selenium deficient, and 4) vitamin A plus selenium deficient. Three hours before being sacrificed, half of the animals were subjected to UV A + B irradiation (3 J/cm2). Superoxide dismutases (SOD), catalase, Se glutathione peroxidase activities were determined in dorsal skin homogenates, as well as the concentrations of GSH and of thiobarbituric acid-reactive substances (TBARS), the latter being an index of lipid peroxidation. Ultraviolet light altered the antioxidant defense of mouse skin tissue: GSH level, catalase and Se glutathione peroxidase activities were lowered and SOD was unequally enhanced according to the nutritional status. Vitamin A and Se deficiencies did not perceptibly aggravate the UV-induced oxidative stress, although the former enhanced the decline of catalase expression induced by the irradiation. Probably through an adaptive mechanism, both dietary deficiencies increased the skin reserve of antioxidant GSH and thus appear to modulate the effects caused by reactive oxygen species.

Animals↗
PubMed1995

Reflecting on reflection: a personal encounter.

This paper reports a retrospective study of a Senior Lecturer in Nursing Studies experience of supervising a student teacher who, as part of her teaching placement experience, utilised 'Critically Reflective Analysis of an Educational Event' as a means to assess her teaching in the practice setting. The Senior Lecturer and student nurse teacher used an external 'advisor' to facilitate their meta-reflection on the theoretical perspectives that informed the process in which they were engaged. The paper raises the following questions for consideration--What is the link between ability to reflect and quality of practice? Is it possible to utilise reflective tutorials as a means of assessing professional competence whilst at the same time encouraging personal and professional development? Is the ability to reflect on practice dependent on the context? Should we assume that all practitioners have the necessary skills to supervise students in practice and what preparation and support is needed? The paper demonstrates that by introducing 'Critically Reflective Analysis of an Education Event' into the student teachers' curriculum the role of both supervisor and student teacher was challenged and changed. The paper also demonstrates that reflective tutorials are not wholly a retrospective business. They are creative, or recreative of a teaching experience, as well as to some extent representing it. Finally, even if one cannot speak in Kuhnian parlance, of a conceptual revolution, it would seem legitimate to say, in Schon's terms, that the contextual frame in which professional problems are addressed has undergone significant change.

Education, Nursing, Baccalaureate↗
PubMed1995

Vitamin A status and metabolism of cutaneous polyamines in the hairless mouse after UV irradiation: action of beta-carotene and astaxanthin.

Solar radiations (UV A and B) can cause epidermis photoaging and skin cancers. These frequently irreversible effects result from the in situ generation of free radicals. However, it has been noted that nutritional factors can modulate photochemical damage, in particular the common carotenoids present in food, which can be considered as potential prophylactic agents against carcinogenesis. We investigated the effect of UV A and B radiations on the skin of the SKH1 hairless mouse fed a diet either lacking in vitamin A or supplemented with retinol, beta-carotene or astaxanthin. The latter is an oxygenated carotenoid (like canthaxanthin) without provitamin A activity and with strong singlet oxygen quenching ability. After analysing of vitamin status of each group (plasma retinol concentrations and hepatic reserves), we searched for UV-induced modifications of polyamine metabolism by measuring epidermal ornithine decarboxylase (ODC) activity and free polyamines concentration (putrescine, spermidine and spermine). In the basal state without irradiation, differences in ODC activity between groups were nonsignificant; but after UV stimulation, ODC increased markedly in the skin of vitamin A-deficient animals, much more than in other groups. Curiously, the addition of astaxanthin or beta-carotene to the regimen containing retinol reduced the protective effect of retinol alone. Regarding polyamines after irradiation, putrescine was significantly increased in the skin of deficient animals, in parallel with ODC activity. However, astaxanthin had a stronger inhibitory effect on putrescine accumulation than retinol, and decreased spermidine and spermine concentrations: this suggests a specific action on transglutaminases.

Animals↗
PubMed1994

Primary cultures of bovine inner zone adrenocortical cells secrete cortisol in response to adenosine triphosphate, adenosine diphosphate, and uridine triphosphate via a nucleotide receptor which may be coupled to two signal generation systems.

Cultured inner zone cells isolated from bovine adrenal cortex secreted cortisol in a dose-dependent fashion in response to ATP and ADP. The threshold response was at 10(-6) M ATP, reaching a maximum by 10(-4) M ATP, at which concentration the n-fold relative to basal was 43.8 +/- 22.3 (mean +/- SD, n = 3). The response to 10(-4) M ATP remained linear for up to 2 h, and the cells appeared morphologically normal after removal of the stimulus. Stimulation of cortisol secretion by ATP was evident after 24 h in primary culture and reached a maximum after 48-72 h, thereafter declining. No response was detected in freshly isolated cells. The possibility that added ATP was degraded over the course of the incubation was investigated by separating ATP, ADP, AMP, and adenosine by high resolution anion exchange chromatography after different times of exposure to the cells. Although there was degradation--largely to ADP--about 50% of the ATP remained at 1 h. The potency order of a range of purines was as follows: ATP = ADP > 2-methyl-S-ATP > alpha, beta-methylene ATP = beta, alpha-methylene ATP = AMP. Cells were also responsive to the pyrimidine nucleotide uridine 5'-triphosphate, which was equipotent with ATP. The purinergic antagonist suramin was relatively ineffective. Cells grown in the presence of [3H]inositol (10 microCi/ml) for 48 h (to prelabel the membrane phosphoinositide pool to isotopic equilibrium) showed a time- and dose-dependent increase in [3H]inositol-labeled total phosphoinositols in response to ATP or ADP; the response was linear for at least 60 min. Cells labelled with the Ca2+ indicator fura-2 showed an increase in intracellular calcium in response to 10(-4) M ATP on days 3 and 4 of culture. Basal intracellular Ca2+ was found to be 57.3 +/- 39.3 nmol/liter (mean +/- SD, n = 12 cell suspensions) rising to 171 +/- 84 nmol/liter (mean +/- SD, n = 12 cell suspensions) in response to ATP (10(-4) M). In response to ATP, bovine inner zone cells also demonstrated a dose-dependent increase in intracellular cAMP measured after 1 min stimulation. It was not possible to account for the cAMP response on the basis of conversion of ATP to adenosine, which then acted at an A2 receptor.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Diphosphate↗
PubMed1994

Primary cultures of bovine inner zone adrenocortical cells secrete cortisol in response to adenosine 5'-triphosphate, adenosine 5'-diphosphate, and uridine 5'-triphosphate via a nucleotide receptor that may be coupled to two signal generation systems.

Cultured inner zone cells isolated from bovine adrenal cortex secreted cortisol in a dose-dependent fashion in response to ATP and ADP. The threshold response was at 10(-6) M ATP, reaching a maximum by 10(-4) M ATP, at which concentration the n-fold increase relative to basal was 43.8 +/- 22.3 (mean +/- SD; n = 3). Cells were also responsive to the pyrimidine nucleotide UTP. EC50 values for ATP, ADP, and UTP were 5.83 +/- 3.98 x 10(-6), 13.7 +/- 5.67 x 10(-6), and 7.33 +/- 4.52 x 10(-7) M, respectively (mean +/- SD; n = 3). The response to 10(-4) M ATP was linear for at least 60 min, and the cells appeared morphologically normal after removal of the stimulus. The purinergic antagonist suramin was relatively ineffective. The potency order of a range of purines was as follows: ATP = UTP > ADP > 2-methyl-S-ATP > alpha, beta-methylene ATP = beta, alpha-methylene ATP = AMP. Stimulation of cortisol secretion by ATP was evident after 24 h in primary culture and reached a maximum after 48-72 h, thereafter declining. No response was detected in static incubations of freshly isolated cells. The possibility that added ATP was degraded over the course of the incubation was investigated by separating ATP, ADP, AMP, and adenosine by high resolution anion exchange chromatography after different times of exposure to the cells. Although there was degradation, largely to ADP, about 50% of the ATP remained at 1 h. Cells grown in the presence of [3H]inositol (10 microCi/ml) for 48 h (to prelabel the membrane phosphoinositide pool to isotopic equilibrium) showed a time- and dose-dependent increase in [3H]inositol-labeled total phosphoinositols to ATP or ADP; the response was linear for at least 20 min. Cells labeled with the Ca2+ indicator fura-2 showed an increase in intracellular calcium to 10(-4) M ATP on days 3 and 4 of culture. The basal intracellular Ca2+ concentration was 57.3 +/- 39.3 nmol/liter (mean +/- SD; n = 12 cell suspensions), rising to 171 +/- 84 nmol/liter (mean +/- SD; n = 12 cell suspensions) after the addition of ATP (10(-4) M). Bovine inner zone cells also demonstrated a dose-dependent increase in intracellular cAMP measured after 1 min of stimulation with ATP. It was not possible to account for the cAMP response on the basis of conversion of ATP to adenosine, which then acted at an A2 receptor.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Diphosphate↗
PubMed1994

[Is the identification of acute biliary and alcoholic pancreatitis by early pancreatic enzyme assay possible?].

Early and appropriate treatment of acute pancreatitis (AP) depends on early causal diagnosis. Published studies have shown favourable results following sphincterotomy performed within the 72 hours of onset of severe gallstone-associated AP. Among the various bio-clinical indices, the lipase/amylase (L/A) ratio, computed within 72 hours after onset, has been shown to discriminate between alcoholic and non alcoholic AP. Our study evaluates the data of biochemical disorders in 51 patients presenting with an episode of AP; these patients were divided into 3 groups: A: alcoholic AP, n = 15; B: biliary AP, n = 25; and C: post-ERCP AP, n = 11. These 3 groups were similar with respect to clinical severity of AP and CT scan. The time delays between onset of the symptoms and the biochemical assay were 1.9 +/- 0.3, 1.9 +/- 0.2 and 0.6 +/- 0.3 d (P < 0.01). AST, ALT, bilirubin, GGT and alkaline phosphatase were significantly (P < 0.05) greater in group B. Blamey's score was 0.5 +/- 0.2, 2.8 +/- 0.2 and 2.5 +/- 0.4 in groups A, B and C respectively. Serum amylase, serum lipase and L/A ratio were identical in groups A and B. The decrease in serum amylase after 48 hours was more important only in group B (56 +/- 8, 80 +/- 4, 47 +/- 3% respectively in groups A, B and C). L/A ratio was significantly greater in group C when compared with group A and B (1.7 +/- 0.4, 1.5 +/- 0.2 and 2.2 +/- 0.3 in groups A, B and C respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1993

[Vitamins and cancers].

To a great extent carcinogenesis depends on the environment. Some vitamins contribute to the "exogenous" protection against aggressors (i.e., on a molecular scale, active forms of oxygen and free radicals). Epidemiology provides numerous data in favour of this protection, but these date are sometimes ambiguous or contradictory. Current, active experimental studies will probably lead to firm conclusions within the next few years. As regards vitamin A, considerable advances have been made in fundamental research (we now know its molecular mechanism of action, notably on genes) and in applied research (differentiation of leukaemic cells). In various aspects vitamin D resembles vitamin A and also acts on the haematopoietic tissue. Vitamin E is difficult to study, but its protective effect on cell membranes and structures cannot be questioned. Vitamin C emerges from a period of controversy and is increasingly studied at present: it might be a useful adjuvant for the treatment of cancers.

Animals↗
PubMed1993

Long-term culture of human pancreatic islets in an extracellular matrix: morphological and metabolic effects.

In this experiment, various conditions for embedding cultures of human pancreatic islets in type I collagen gel were studied in an attempt to maintain the highly differentiated functions of islet cells and particularly insulin secretion over a long period of time. The islets isolated by a collagenase digestion technique were plated either on or within the collagen gel and refed with either Eagle's minimum essential medium (5.5 mM D-glucose) or RPMI 1640 medium (11 mM D-glucose) supplemented with 10% FCS and antibiotics. The comparison between the two culture media showed that embedded islets cultured in RPMI had a higher basal insulin secretion rate, survived longer than their MEM counterparts, but exhibited impaired response to an acute glucose test contrasting thus with islets cultured in MEM. The secretory behaviour of islets was also related to the different morphological modifications occurring during culture. Islets directly embedded within the collagen gel more or less maintained their spherical structure and highest secretory capacities. When overlaid with a second layer of collagen, well established monolayers of human islet cells grown on collagen underwent a gradual and complete reorganization into a three-dimensional islet-like structure with a striking reinforcement of their secretory activity. Both cultures were able to survive more than 8 weeks, thus proving the usefulness of such a new model for long-term culture. In contrast, standard cultures on culture treated plastic dishes on which islets cells rapidly established wide monolayers, exhibited a rapid and definitive decline in insulin secretion with a survival not exceeding 14 days. In the light of these different culture conditions, possible mechanisms responsible for disturbance of hormonal release and their implications for in-vitro study of isolated islets functions are discussed. In conclusion, this work is a new example of the permissive effects of collagen matrices on the establishment or maintenance of tissue-like structures in vitro, suggesting the definition of a new model for the study of human pancreatic islets in long-term culture.

Adult↗
PubMed1993

Hormonal study of a human mixed follicular and medullary thyroid carcinoma.

We studied the hormonal secretion of a human mixed follicular and medullary carcinoma. Thyroglobulin (Tg) secretion, especially by large cells and sometimes by small ones, was visualized with immunoenzymatic staining. Calcitonin (CT) was produced by small spindle-shaped cells. Moreover, immunofluorescence double staining performed on the resected thyroid tissue showed the secretion of both Tg and CT in a small number of cells. The cells lost their hormonal secretion after 2 months of culture. Hormonal secretion was modulated by different additives in the medium. Tg secretion was induced when TSH was added to the culture medium; the maximal effect was produced with the addition of 1 mU TSH/ml and 1 microM cortisol, which potentiated the effect of TSH on Tg production. A durable Tg secretion was obtained by embedding the cells in Engelbretch-Hohn-Swarn (EHS) tumour matrix. The CT production was reinduced by the addition of 4 mM Ca2+, 1 microM glucagon and 1 microM cortisol to the culture medium. These findings show that different cells are found in a mixed follicular and medullary carcinoma, some of which can secrete both CT and Tg. They can remain differentiated for a long period after being embedded in EHS tumour matrix with Ca2+ and hormonal components.

Adenocarcinoma, Follicular↗
PubMed1993

Acid-base responses to high-volume haemofiltration in the critically ill.

We have studied the acid-base and cardiorespiratory effects of intermittent pumped high-volume venovenous haemofiltration (HVHF) using replacement fluid containing lactate as the source of bicarbonate in critically ill patients. We demonstrated significant hyperlactataemia throughout the procedure, but there was no deterioration in acid-base status, haemodynamics, or oxygen delivery. These observations suggest that the worsening of acidosis and the hypotension that have been described with this technique can be avoided by appropriate monitoring and resuscitation prior to haemofiltration, and may be due to unrecognized inadequacies in the oxygen transport system.

Acid-Base Imbalance↗
PubMed1993

Hepatic or pulmonary ornithine decarboxylase and vitamin A status in Wistar rat, enzyme kinetics--influence of chloroform.

The ODC activity, initial enzyme in the polyamines synthesis, was studied in the liver and lungs of Wistar rat under avitaminosis A. In the liver: ODC activity is decreased by vitamin A deficiency but partially recovered with retinol repletion during 2 weeks. An intraperitoneal injection of chloroform markedly stimulates the ODC activity, as in the deficient rat as in the normal animal; the response following stimulation is even relatively higher under avitaminosis A. The Km value of ODC increases in the deficiency; intermediate values are obtained in retinol repletion. However the chloroform injection has no effect on the Km values under any of the nutritional state. In the lungs: The baseline ODC activity is slightly decreased in the deficient animals. The chloroform stimulation induced relatively a moderate increase in the normal rat (2 fold over baseline level); it is more intense (4 fold) in deficient animal and the ODC activity is well above those of normally fed control in absolute value. As in the liver, the enzyme Km increases in avitaminosis A and a retinol repletion partially attenuates this influence. Here again, the chloroform stimulation has no effect on the Km values.

Animals↗
PubMed1993

[Vitamins and immunity].

Nutritional status conditions immunity in man whom malnutrition is often associated with diminished immunocompetence and increased susceptibility to infection. Among micronutrients, vitamins A, C, E and carotenoids notably have special influence: they provide good cellular and tissular physiological behaviour; they also protect tissues against reactive oxygen species, and enhance immune response.

Antioxidants↗
PubMed1992

The relationship of blood lactate concentrations, oxygen delivery and oxygen consumption in septic shock and the adult respiratory distress syndrome.

Tissue hypoxia is thought to be pivotal to the development of multiple organ failure, but cannot be measured directly in clinical practice. We assessed the relationship between initial arterial blood lactate concentrations and the presence of the phenomenon of delivery-dependent oxygen consumption, both of which may indicate tissue hypoxia. Twenty-three critically ill patients with septic shock and adult respiratory distress syndrome were studied prospectively and allocated to one of two groups according to blood lactate concentrations. In group 1, blood lactate concentration was less than the level widely accepted as significant (2 mmol.l-1); in group 2, the concentration exceeded 2 mmol.l-1. In both groups, resuscitation with colloid, blood and vasoactive drugs resulted in significant increases in oxygen delivery; in group 1 (n = 13), mean (SEM) oxygen delivery increased from 484 (36) to 730 (44) ml.min-1.m-2 (p < 0.005) and in group 2 (n = 10) from 550 (54) to 780 (54) ml.min-1.m-2 (p < 0.05). In neither group was there a significant change in oxygen consumption. However, there were individuals in both groups who exhibited pathological delivery dependence. This suggests that the absence of hyperlactataemia does not preclude delivery dependence of oxygen consumption with the attendant potential for tissue hypoxia.

Adult↗
PubMed1992

Interleukin-1 beta stimulates growth of adrenocortical cells in primary culture.

Using tritiated-thymidine incorporation as a measure of cell growth, interleukin-1 beta stimulated the growth of bovine zona fasciculata/reticularis adrenocortical cells after 72 h in primary culture. Within the range of 10-1000 pg/ml, interleukin-1 beta produced over 40% of angiotensin II-stimulated [3H]thymidine incorporation (P less than 0.005 compared with basal for 10 pg/ml and 1000 pg/ml; P less than 0.05 for 100 pg/ml; two-tailed unpaired Student's t-test). Interleukin-1 beta did not directly stimulate cortisol secretion. By stimulating adrenocortical growth, the increase in interleukin-1 during fever provides a potential mechanism for chronically raising glucocorticoid output. This study is the first demonstration of a long-term effect involving interleukin-1 beta on the adrenal cortex.

Animals↗
PubMed1992

Effects of cisplatin on human thyrocytes in monolayer or follicle culture.

Cis-diamminedichloroplatinum (II) (cisplatin) is a widely used anticancer drug which induces many side-effects, but its action on the thyroid gland is still unknown. We have investigated the effects of this drug on human thyrocytes cultured in monolayers or in follicles and stimulated with 200 microU TSH/ml. After 72 h in culture, different concentrations of cisplatin (15, 30 and 75 microM) caused partial or total inhibition of cyclic AMP (cAMP), thyroglobulin (Tg) and tri-iodothyronine (T3) production, whereas thyroxine levels increased in the medium of thyrocytes cultured as follicles. Small doses of the drug did not affect thyrocyte production. Decreases in neutral-red uptake by thyroid cells and in intracellular lactate dehydrogenase, alpha-hydroxybutyryldehydrogenase and creatine phosphokinase activities were induced by 30 and 75 microM cisplatin. These data show that high concentrations of cisplatin had a cytotoxic effect on thyrocytes. Cisplatin also induced inhibition of the production of cAMP, Tg and T3.

Cells, Cultured↗
PubMed1992

[Use of cultures of human thyroid cells in physiopathology and pharmacotoxicology].

We reconstituted functional follicles from isolated cells, after embedding in a collagen matrix. Therefore we could carry out many investigations. We showed that the cells embedded in collagen reorganized into functional follicles secreting thyroglobulin (Tg) visualised in the intra-follicular compartment, and triiodothyronine (T3) after TSH stimulation. We used these reconstituted follicles for testing several drugs, amiodarone, propranolol and some anaesthetic drugs (thiopental, midazolam and ketamine). We observed that all these drugs inhibited partially or totally, according to the dose administered, the follicular production of Tg and T3. We also found that the follicles reconstituted from thyroid Grave's tissues gave an abnormal secretion of Tg and T3. Finally we created in Rennes a human thyroid model that permits the exploration of pathologic tissues and that may be used in pharmacotoxicology.

Amiodarone↗