MRSA is bigger than us.
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Decontamination↗
Biomedical subjects
P Sanderson
Publications and source records attributed to P Sanderson.
Extracellular release of free fatty acids by rat T lymphocytes is stimulus-dependent and is affected by dietary lipid manipulation.
[(3)H]-Arachidonic acid-labelled rat T lymphocytes released radioactivity extracellularly when stimulated by the calcium ionophore A23187 or by monoclonal antibodies to some cell surface structures (CD2, CD5, CD11a, CD18, CD54, T-cell receptor) but not to others (CD49d, CD62L); release was greater with the calcium ionophore. Almost all of the radioactivity released from anti-CD2-stimulated lymphocytes was recovered in the free fatty acid fraction, whereas only about 50 per cent of that released after A23187 stimulation was recovered in this fraction. A23187 stimulation resulted in release of arachidonic acid from a variety of phospholipids (phosphatidylinositol, phosphatidylcholine and perhaps phosphatidylethanolamine), while the monoclonal antibody stimulation released arachidonic acid from phosphatidylinositol and perhaps phosphatidylcholine. Unstimulated lymphocytes released a range of fatty acids extracellularly, with palmitic acid accounting for 35-40 per cent and arachidonic acid for 5 per cent of released fatty acid. Stimulation of lymphocytes with either anti-CD2 or A23187 increased total fatty acid release 1.5- to 1.8-fold. In both cases palmitic acid remained the most predominant fatty acid released but the contribution of arachidonic acid increased. The type of lipid fed to the rats significantly influenced the amount and type of fatty acid released. Fish oil feeding significantly reduced extracellular fatty acid release by stimulated lymphocytes.
Animals↗
Dietary fish oil appears to prevent the activation of phospholipase C-gamma in lymphocytes.
Rats were fed on a low fat diet or on high fat diets which included coconut oil, olive oil, safflower oil, evening primrose oil or fish oil as the principal fat source. The level of phosphatidylinositol-4, 5-bisphosphate in spleen lymphocytes was unaffected by diet. However, the fish oil diet significantly decreased the concentration of inositol-1,4,5-trisphosphate in stimulated lymphocytes; this concentration was also reduced following olive oil feeding. Diet did not significantly affect the level of phospholipase C-gamma1 in spleen lymphocytes but the tyrosine phosphorylation state of this enzyme in stimulated lymphocytes, as well as that of a range of other proteins, was decreased following feeding the fish oil and, to a lesser extent, the olive oil diets. It is concluded that fish oil feeding appears to result in inhibition of one or more tyrosine kinases.
Animals↗
Inhibition of vasopressinergic neurons by central injection of a specific aminopeptidase A inhibitor.
The brain angiotensin (Ang) system plays an important role in the central control of vasopressin release. Using EC33, a selective aminopeptidase A inhibitor which blocks the metabolism of Ang II in Ang III, we previously reported that vasopressin release was under the control of Ang III and not Ang II. To determine accurately the action of EC33, the effects of intracerebroventricular injection of Ang peptides or EC33 on extracellular unit activity of vasopressinergic neurons in the supraoptic nucleus of urethane-anaesthetized rats were examined. Angiotensin II (15-30 ng) or Ang III (15 ng) increased the firing rate of all neurons tested. Conversely, EC33 (10 microg) reduced or completely abolished (30-60 microg) the basal firing rate for 4-6 min in all eight neurons tested. EC33 (30 microg) also inhibited the activity induced by 30 ng Ang II. It was concluded that the observed activity of Ang II required its conversion to Ang III and that endogenous Ang III may exert a tonic control on the basal firing level of vasopressinergic neurons.
Aminopeptidases↗
N-acetylcysteine prevents development of the hyperdynamic circulation in the portal hypertensive rat.
Partial portal vein ligation (PPVL) leads to the development of a hyperdynamic circulation. It is associated with elevated levels of tumor necrosis factor (TNF-alpha) and nitric oxide (NO) production, both of which can result in oxidant injury. In this study, we have investigated whether PPVL is associated with the development of oxidative stress, by measuring urinary F2-isoprostanes. In addition, we have examined whether N-acetylcysteine (NAC) can ameliorate oxidant injury and prevent the development of the hyperdynamic circulation. Urinary excretion of F2-isoprostanes increased sixfold following PPVL together with a significant increase in plasma nitrite and nitrate. Treatment with NAC inhibited the formation of F2-isoprostanes as well as the increase in plasma nitrite and nitrate. Hemodynamic studies in anesthetized rats showed that following PPVL, cardiac output and portal pressure increased, and systemic vascular resistance decreased, consistent with the development of a hyperdynamic circulation. These changes were prevented by chronic administration of NAC. We conclude that NAC prevents the development of the hyperdynamic circulation and that the formation of reactive oxygen species may be important in the pathogenesis of these hemodynamic changes.
Acetylcysteine↗
Eicosapentaenoic and docosahexaenoic acids alter rat spleen leukocyte fatty acid composition and prostaglandin E2 production but have different effects on lymphocyte functions and cell-mediated immunity.
Weanling rats were fed on high-fat (178 g/kg) diets which contained 4.4 g alpha-linolenic (ALA), gamma-linolenic, arachidonic (ARA), eicosapentaenoic (EPA), or docosahexaenoic acid (DHA)/100 g total fatty acids. The proportions of all other fatty acids, apart from linoleic acid, and the proportion of total polyunsaturated fatty acids (PUFA) (approximately 35 g/100 g total fatty acids) were constant, and the n-6 to n-3 PUFA ratio was maintained as close to 7 as possible. The fatty acid compositions of the serum and of spleen leukocytes were markedly influenced by that of the diet. Prostaglandin E2 production was enhanced from leukocytes from rats fed the ARA-rich diet and was decreased from leukocytes from the EPA- or DHA-fed rats. Replacing dietary ALA with EPA resulted in diminished ex vivo lymphocyte proliferation and natural killer (NK) cell activity and a reduced cell-mediated immune response in vivo. In contrast, replacing ALA with DHA reduced ex vivo lymphocyte proliferation but did not affect ex vivo NK cell activity or the cell-mediated immune response in vivo. Replacement of a proportion of linoleic acid with either gamma-linolenic acid or ARA did not affect lymphocyte proliferation, NK cell activity, or the cell-mediated immune response. Thus, this study shows that different n-3 PUFA exert different immunomodulatory actions, that EPA exerts more widespread and/or stronger immunomodulatory effects than DHA, that a low level of EPA is sufficient to influence the immune response, and that the immunomodulatory effects of fish oil may be mainly due to EPA.
Animals↗
Low levels of eicosapentaenoic and docosahexaenoic acids mimic the effects of fish oil upon rat lymphocytes.
Fish oil is rich in the long chain n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); typically these fatty acids constitute 20 to 25 g/100 g total fatty acids in fish oil. Feeding rodents diets rich in fish oil has been shown to decrease lymphocyte proliferation and natural killer cell activity. It is not known what level of EPA + DHA is required in the diet to exert these effects. This question was addressed in the current study. Weanling rats were fed on high fat (178 g/kg) diets which contained 4.4 g alpha-linolenic acid (control) or 4.4 g EPA + DHA (4.4 EPA + DHA) or 6.6 g EPA + DHA (6.6 EPA + DHA)/100 g total fatty acids. The n-6 to n-3 polyunsaturated fatty acid ratio was maintained at approximately 7. The fatty acid compositions of the serum and of spleen leukocytes were markedly influenced by that of the diet. Spleen lymphocyte proliferation in response to concanavalin A, spleen natural killer cell activity and PGE2 production by spleen leukocytes were reduced by feeding the EPA + DHA diets compared with feeding the control diet; the 4.4 and 6.6 EPA + DHA diets caused very similar reductions. The 4.4 EPA + DHA diet reduced popliteal lymph node weight following a localised graft versus host response; this response was not investigated in rats fed the 6.6 EPA + DHA diet. The reductions in lymphocyte functions and in the in vivo graft versus host response caused by the EPA + DHA diets were similar to those previously reported following the feeding of diets rich in fish oil. Thus, this study shows that diets containing relatively low levels of EPA + DHA (20 to 25% of the level found in fish oil) exert immunomodulatory effects. Furthermore, this study suggests that the maximal effect of EPA + DHA is exerted when these fatty acids constitute a level of less than or equal to 4.4 g/100 g total dietary fatty acids.
Animals↗
Dietary fish oil diminishes lymphocyte adhesion to macrophage and endothelial cell monolayers.
To further investigate the immunomodulatory effects of dietary lipids, rats were fed on a low-fat diet or on high-fat diets that contained hydrogenated coconut, olive, safflower, evening primrose or fish oil as the principal fat source. The fish oil diet decreased the level of expression of CD2, CD11a, CD18 and CD44 on the surface of freshly prepared lymphocytes and of CD2, CD11a, CD18, CD54 (intercellular adhesion molecule-1; ICAM-1) and CD62L (L-selectin) on the surface of concanavalin A (Con A)-stimulated lymphocytes. The olive oil diet also resulted in decreased expression of some adhesion molecules. The fish or olive oil diets, and to a lesser extent the safflower or evening primrose oil diets, decreased the adhesion of both freshly prepared and Con A-stimulated lymphocytes to macrophage monolayers. The fish oil diet, and to a lesser extent the olive or evening primrose oil diets, reduced the ability of Con A-stimulated lymphocytes to adhere to untreated endothelial cells. Furthermore, the fish oil diet resulted in a 50% reduction in Con A-stimulated lymphocyte adhesion to tumour necrosis factor-alpha (TNF-alpha)-stimulated endothelial cells. This study demonstrates that dietary lipids affect the expression of functionally important adhesion molecules on the surface of lymphocytes. Furthermore, this study suggests that such diet-induced effects on adhesion molecule expression might alter the ability of lymphocytes to bind to macrophages and to endothelial cells. Of the diets studied fish oil causes the most significant effects. The results of this study suggest that a reduction in cellular infiltration may partly explain the protective effect of a fish-oil-rich diet against the development of inflammatory and cardiovascular diseases.
Animals↗
Closed circuit anaesthesia in ventilated patients using the Komesaroff vaporizer within the circle.
A study was undertaken to assess the performance of the Komesaroff vaporizer, placed within the circuit, in ventilated patients during maintenance of closed circuit anaesthesia with halothane or isoflurane. Following intravenous induction, anaesthesia was maintained by inhalation. This was achieved using a conventional vaporizer outside the circle for the first 10 minutes to manage the fast uptake phase. The fresh gas flow was then reduced to the basal oxygen requirement with the Komesaroff vaporizer within the circle maintaining inhalational anaesthesia. Complete isolation of the circuit was achieved by returning all anaesthetic gases to the circuit following analysis and using a bag-in-bottle ventilator. The Komesaroff vaporizer dial was positioned at between the first and second division and end-tidal volatile anaesthetic agent levels were measured. This study demonstrated that at dial positions 1 or 1.5 with either agent, the end-tidal volatile concentration plateaued at clinically acceptable levels. The Komesaroff vaporizer can therefore be used safely in ventilated patients to maintain closed circuit anaesthesia provided clinical observation and monitoring are meticulous.
Adult↗
Electromyographic biofeedback for gait training after stroke.
OBJECTIVE: To examine the effects of electromyographic (EMG) biofeedback training on the recovery of gait in the acute phase post stroke. DESIGN: Patients were randomly assigned to EMG biofeedback or control groups. They received treatment three times a week for six weeks. All patients were assessed prior to treatment, after 18 treatment sessions, and at three months follow-up. SETTING: The study was carried out at Scunthorpe General Hospital in North Lincolnshire. The subjects were acute stroke patients who had been admitted on to the medical and elderly wards. INTERVENTIONS: The EMG biofeedback group were treated using EMG as an adjunct to physiotherapy. The patients were encouraged to facilitate or inhibit abnormal muscle tone via auditory or visual signals transmitted from electrodes placed over the appropriate muscles. The control group were treated using the same techniques, electrodes were used with this group of patients, but the EMG machine was turned off and faced away from the patient and the therapist to control the placebo effect. OUTCOME MEASURES: A large battery of outcome measures was used for physical and psychological assessment. The physical measures consisted of active movement, muscle tone, sensation, proprioception, mobility and activities of daily living (ADL). The psychological measures included orientation, memory, spatial performance, language and IQ. RESULTS: Twenty-one patients were included in the study. Scores were combined into four groups: mild EMG, severe EMG, mild control and severe control. Results showed that there was an improvement in physical scores for active movement, mobility and ADL over time, but there was no significant difference between the EMG and control groups. Scores on the psychological tests were within normal limits, and there was no difference in performance between the EMG and control groups. CONCLUSIONS: This study showed no significant differences in the rate of improvement after stroke between the two groups. Although EMG biofeedback was used as an adjunct to physiotherapy and represented clinical practice, the results provide little evidence to support the clinical significance of using EMG biofeedback to improve gait in the acute phase after stroke.
Activities of Daily Living↗
Effects of varying the type of saturated fatty acid in the rat diet upon serum lipid levels and spleen lymphocyte functions.
To obtain further information about the effects of specific dietary saturated fatty acids, weanling male rats were fed for 6 weeks on low fat (7.7% by weight) or high fat (17.8% by weight) diets which differed according to the principal fatty acids present. The diets were rich in caprylic and capric acids (medium chain triacylglycerols; MCT), lauric acid, palmitic acid at the sn-1(3) position, palmitic acid at the sn-2 position or stearic acid. The total proportions of saturated (42-46%), monounsaturated (36%), n-6 polyunsaturated (15%) and n-3 polyunsaturated (2.2%) fatty acids were the same in all diets. Serum cholesterol concentrations were not different among rats fed the different diets, except that the concentration in the serum of rats fed the high fat diet with palmitic acid in the sn-2 position was high. This was reflected in higher HDL and LDL cholesterol concentrations in the serum of animals fed this diet. Triacylglycerol (TAG) concentrations tended to be higher in the serum of rats fed the low fat diets compared with those fed the high fat diets. They were lowest in the serum of MCT-fed rats irrespective of the level of fat in the diet and were highest in the serum of rats fed the low fat diet rich in stearic acid. These differences were due to lower chylomicron and VLDL TAG concentrations in the serum of MCT-fed rats and higher chylomicron and VLDL TAG concentrations in the serum of low fat, stearic acid-fed animals. The fatty acid compositions of the serum and of spleen lymphocytes were influenced by that of the diet fed. The ex vivo proliferation of lymphocytes from the spleens of rats fed the high fat diet rich in palmitic acid at the sn-2 position was greater than that of lymphocytes from animals fed the other diets. Natural killer (NK) cell activity tended to be lower for spleen lymphocytes from rats fed high fat diets than for those fed low fat diets irrespective of the principal saturated fatty acid present. NK cell activity was highest for spleen lymphocytes from animals fed the diets rich in palmitic acid and was lowest for those from animals fed the high fat diet rich in stearic acid. Spleen lymphocytes from the latter animals had the lowest proportion of CD16+ cells, a marker for NK cells. Thus, this study shows that the type of saturated fatty acid present in the diet not only has subtle effects upon blood lipid and lipoprotein levels but can significantly affect lymphocyte functions. Spleen lymphocyte NK cell activity is decreased as the fat content of the diet increases. NK cell number and activity are reduced by a high fat diet rich in stearic acid. Spleen lymphocyte proliferation is enhanced by palmitic acid-rich diets, particularly if palmitic acid is in the sn-2 position of dietary TAG.
Animals↗
Dietary fish oil diminishes the antigen presentation activity of rat dendritic cells.
Rats were fed for 6 weeks on a low fat (LF) diet or on high fat diets containing safflower oil [SO; rich in n-6 polyunsaturated fatty acids (PUFAs)] or fish oil (FO; rich in n-3 PUFAs). Lymph-borne dendritic cells (L-DC) were isolated after cannulation of the thoracic duct and were used as antigen [keyhole limpet hemocyanin (KLH)]-presenting cells in an ex vivo assay that used KLH-sensitized spleen lymphocytes as the responder cells. FO feeding significantly diminished the antigen presentation activity of L-DC compared with L-DC from rats fed each of the other diets. The antigen presentation activity of L-DC from rats fed the SO diet was greater than that of L-DC from rats fed the LF diet. Feeding the FO diet significantly reduced both the proportion of CD2-positive L-DC and the level of CD2 expression on L-DC compared with feeding each of the other diets; the proportions of L-DC staining positive for CD40, CD18, CD54, CD11a, and MHC II were unaffected by diet. However, FO feeding reduced the level of expression of CD18, CD11a, MHC II, and CD54 on L-DC compared with feeding the other two diets; the level of expression of CD40 was unaffected by diet. This is the first study to report effects of dietary fatty acids on dendritic cells. The suppressive effect of FO feeding may account for some of the beneficial effects of n-3 polyunsaturated fatty acids observed in clinical settings, such as prolonged survival of grafts and diminished chronic inflammatory responses. However, such an effect may also be detrimental because host defense toward bacterial and other antigens could be compromised.
Animals↗
Do patients with Clostridium difficile need to be isolated?
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Cross Infection↗
Dietary fish oil diminishes the antigen presentation activity of rat dendritic cells.
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Analysis of Variance↗
The ratio of n-6 to n-3 polyunsaturated fatty acids in the rat diet alters serum lipid levels and lymphocyte functions.
Previous studies have reported that feeding rats diets rich in fish oils, which contain high proportions of the n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic and docosahexaenoic acids, results in lowering of blood lipid levels and suppression of lymphocyte functions tested ex vivo and in vivo. The effects of other n-3 PUFA, such as alpha-linolenic acid, which is found in high proportions in linseed oil, are not as well documented. Therefore, in the present study, weanling male rats were fed for six weeks on one of five high-fat (20% by weight) diets made by mixing together sunflower and linseed oils; the resulting blends had n-6/n-3 PUFA ratios of 112.5:1 (pure sunflower oil), 14.8:1, 6.5:1, 0.81:1, and 0.33:1 (pure linseed oil); the levels of all other components in the diet were identical. The final body weight and total dissectable fat were lowest in rats fed the pure linseed oil diet. Serum cholesterol, triacylglycerol and nonesterified fatty acid concentrations decreased as the n-6/n-3 PUFA ratio of the diet decreased. The fatty acid composition of the serum and of spleen lymphocytes was influenced by the diet fed-there was a progressive decrease in the proportions of linoleic and arachidonic acids and a progressive increase in the proportion of alpha-linolenic acid as the n-6/n-3 PUFA ratio of the diet decreased. Eicosapentaenoic and docosahexaenoic acids were detected in the serum but not in spleen lymphocytes. Inclusion of alpha-linolenic acid in the diet resulted in significant suppression of spleen lymphocyte proliferation in response to the T-cell mitogen concanavalin A and in spleen lymphocyte natural killer cell activity, both measured ex vivo. The localized graft vs. host response, a measure of cell-mediated immunity in vivo, progressively decreased as the n-6/n-3 PUFA ratio of the diet decreased. Thus, this study shows that dietary alpha-linolenic acid results in lowered blood lipid levels and suppressed lymphocyte functions ex vivo and in vivo. With respect to these effects, alpha-linolenic acid is as potent as dietary fish oil.
Animal Feed↗
The effect of varying the omega-6: omega-3 ratio of the diet upon immune function in the rat.
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Animals↗
The significance of an absent ankle reflex.
We assessed the prevalence of abnormal ankle reflexes in 1074 adult patients attending orthopaedic clinics and related it to age. Those with possible pathological causes of reflex loss were excluded. The absence of one or both reflexes was significantly related to increasing age; all patients under 30 years had both reflexes. Few had absent reflexes between 30 and 40 years, but over 40 years, the proportion with both reflexes absent increased rapidly from 5% (40 to 50 years) to 80% (90 to 100 years). Unilateral absence did not show the same pattern of increase being 3% to 5% at 40 to 60 years and 7% to 10% at over 60 years. Our results suggest that a significant number of 'normal' adults have unilateral absence of an ankle reflex, but this finding is rare enough to be a definite clinical sign, irrespective of age.
Adolescent↗
Effects of dietary lipid manipulation upon graft vs host and host vs graft responses in the rat.
The popliteal lymph node (PLN) assay was used to establish whether dietary lipids with differing fatty acid compositions could affect cell-mediated immunity in the rat. Weanling rats were fed for 4 weeks on a lowfat (2.5% by weight; LF) diet or on diets containing 20% (by weight) hydrogenated coconut oil (HCO), olive oil (OO), safflower oil (SO), evening primrose oil (EPO), or menhaden (fish) oil (MO). Feeding the MO diet suppressed the graft vs host response compared with feeding the LF, HCO, SO, or EPO diets, while feeding the OO diet suppressed this response compared with feeding the LF or EPO diets. Feeding the MO diet suppressed the host vs graft response compared with feeding each of the other diets. Following the graft vs host reaction, PLN lymphocytes from animals fed the MO diet had significantly lower levels of expression of LFA-1 and CD2 compared with PLN lymphocytes from animals fed the LF diet; furthermore, they had lower levels of expression of T-cell receptor (TcR), CD4, CD8, LFA-1, and CD2 compared with lymphocytes from animals fed some, and in the case of CD2 each, of the other high-fat diets. Feeding the MO diet resulted in a lower proportion of cells expressing the interleukin-2 receptor, indicating an inhibition of lymphocyte activation, and a lower proportion of CD16+/CD3- cells, indicating a decrease in the proportion of NK cells within the PLN. Following the host vs graft reaction, PLN lymphocytes from animals fed the MO diet had significantly lower levels of expression of TcR and CD8 compared with lymphocytes from animals fed each of the other diets; furthermore, they had lower levels of expression of CD4, CD2, and LFA-1 compared with lymphocytes from animals fed the LF, HCO, OO, or SO diets. These observations indicate that the smaller PLN size of animals fed the MO diet results from an inhibition of activation and subsequent proliferation of cells within the node and perhaps also a suppression of movement of cells from the bloodstream to the PLN, due to decreased level of expression of adhesion molecules. These lowered levels of expression might be due to an inhibitory effect of the n-3 polyunsaturated fatty acids found in MO upon components of the signal transduction pathways involved in lymphocyte activation or upon expression of the genes for the surface molecules or both.
Animals↗