Bowel habit, diet and body weight in preadolescent children.

BACKGROUND: The possible influence of diet and body weight on bowel habit in children is unknown. The present study aimed to investigate the inter-relationships between bowel function, excess body weight and dietary intake in a group of preadolescent children. METHODS: Eighty-four preadolescent children aged 7-10 years were recruited [mean (SD) age 9.7 (1.0) years]. All children completed a bowel habit diary, examining specific parameters of bowel function and a weighed food inventory concurrently for seven consecutive days. Height and weight measurements were also taken. Children were grouped according to whether they met dietary recommendations and by overweight status; differences in bowel function between the groups were then analysed. RESULTS: Children who exceeded reference values for fat were more likely to report an incidence of straining to start (P = 0.005) and pain during defaecation (P = 0.021). Subjects who met protein recommendations were less likely to report incomplete evacuation (P = 0.000) and those who met zinc recommendations were less likely to report pain during defaecation (P = 0.044). Excess body weight (according to International Obesity Task Force cut-offs) was also associated with poor bowel habit, with overweight and obese children reporting lower defaecation frequency and a higher incidence of straining and feelings of incomplete evacuation, although these findings were not statistically significant. Defaecation frequency in healthy children was 1.4 defaecations per day compared to 1.2 defaecations for overweight and obese children. CONCLUSION: A poor diet that fails to meet dietary recommendations as well as being overweight and obese appears to be associated with increased defaecation problems in preadolescent children.

A Randomized, controlled, crossover trial to investigate times to onset of the perception of soothing and cooling by over-the-counter heartburn treatments.

This was a randomized, controlled, four-way crossover study in 45 subjects with a tendency to suffer from moderate heartburn following some meals. The study was designed to assess the time to onset of the perceived soothing and cooling effects of the alginate raft-forming products, Gaviscon Liquid (peppermint), Gaviscon Double Action Liquid (peppermint) and Gaviscon Powder Formulation (fresh tropical), compared with a non-active sublingual control. All three Gaviscon products provided significantly faster soothing and cooling effects compared with the control. Based on the upper 95% confidence limits for the median, time to onset of soothing was perceived within 3.15 min, 3.08 min and 4.05 min for Gaviscon Liquid, Double Action Liquid and Powder Formulation, respectively. Similarly, time to onset of cooling was perceived within 1.95 min, 1.23 min and 11.22 min for Gaviscon Liquid, Double Action Liquid and Powder Formulation, respectively. The results show that Gaviscon Liquid and Gaviscon Double Action soothe within 3.15 min and cool within 1.95 min.

The online Cough Clinic: developing guideline-based diagnosis and advice.

The aim of the present study was make chronic cough guidelines more practical and user friendly by developing an internet-based interactive diagnostic questionnaire for chronic cough. A prospective cohort study of chronic cough sufferers was conducted in the UK, following European Respiratory Society guidelines for the diagnosis and management of chronic cough. Depending on the response to 16 specific questions, the medical condition responsible for the patient's chronic cough was ascertained according to a predetermined diagnostic algorithm designed to differentiate the three common causes of chronic cough. Appropriate advice and treatment recommendations were then provided. 8,546 adults with chronic cough completed the Cough Clinic diagnostic questionnaire. 46.1% were suggested to have reflux, 38.7% asthma and 15.2% rhinitis. Participants found the website easy to use (94%), the advice helpful (73%) and that it helped them to communicate with their general practitioner better (60%), and 62% reported taking the recommended treatment. The Cough Clinic, an internet-based diagnostic site for chronic cough, had a large uptake by chronic cough sufferers in the UK. Almost half were diagnosed as having reflux as the probable cause of their chronic cough. Internet diagnosis by expert algorithm provides a novel mechanism for patients to access guideline-recommended therapies and enhances dialogue between patients and physicians.

Habitual micronutrient intake during and after pregnancy in Caucasian Londoners.

Micronutrient status is of fundamental importance both upon conception and throughout pregnancy. There is an abundance of literature investigating nutrient intakes during individual trimesters of pregnancy but few studies have investigated baseline intakes of nutrients throughout gestation as a continuum. The current investigation set out to measure habitual micronutrient intakes at weeks 13, 25, 35 of pregnancy and 6 weeks postpartum using a prospective background information questionnaire, 4-7-day weighed food diary and postnatal questionnaire. Seventy-two primiparous, Caucasian Londoners were recruited at the study start with 42 completing the first, second, third trimester and postpartum study stages respectively. Study findings indicated that sodium intakes were significantly higher than UK guidelines throughout and after pregnancy (P < 0.001). Intakes of folate, iron, vitamin D, potassium, iodine and selenium were lower than UK recommendations during and after pregnancy, but to varying levels of statistical significance (P < 0.05). Only 23-38% of women met UK recommendations for folate (300 microg day(-1)) through dietary sources. Similarly, only a small percentage of women met dietary guidelines for iron (19-28%). The findings from the current study indicate that public health interventions may be required to help expectant mothers achieve an optimal diet, particularly after birth when dietary recommendations increase for some micronutrients.

Thickness and continuity of the adherent colonic mucus barrier in active and quiescent ulcerative colitis and Crohn's disease.

BACKGROUND: The colon is covered by a mucus barrier that protects the underlying mucosa and alterations in this mucus barrier have been implicated in the aetiology of inflammatory bowel disease (IBD). This study investigated the thickness and continuity of the mucus barrier in ulcerative colitis (UC) and Crohn's disease (CD) in comparison to normal controls. METHODS: Rectal biopsies were taken from 59 patients and cryostat sections stained with periodic acid-Schiff's/Alcian blue to visualise the mucus layer. Mucus thickness and continuity and goblet cell density were measured using light microscopy. RESULTS: An essentially continuous adherent mucus layer was observed in normal human rectum and there was no change in the mucus barrier in quiescent UC. In active UC there was a trend for the mucus layer to become progressively thinner and significantly more discontinuous as disease severity increased. In severe active UC the mucus layer thickness and goblet cell density were significantly reduced compared with normal controls while the percentage discontinuity significantly increased. CONCLUSION: It is not until severe UC that there is a global change in mucosal protection as a consequence of large regions lacking mucus, a decrease in secretory potential caused by a loss of goblet cells and a thinner, less effective mucus layer even when it is present.

Administration of an alginate based gastric reflux suppressant on the bioavailability of omeprazole.

BACKGROUND & OBJECTIVE: Omeprazole treats gastro-oesophageal reflux disease (GORD) by inhibition of acid secretion whereas alginate based reflux suppressants work by forming a low density raft of near neutral pH which floats on the stomach contents and physically impedes gastro-oesophageal reflux. There is limited pharmacokinetic information regarding possible drug interaction between these two types of products, although these may be frequently co-prescribed to improve symptom control in GORD patients. This study was designed to determine whether the administration of a 10 per cent w/v liquid alginate suspension affected the pharmacokinetic profile of omeprazole. METHODS: This was a randomized, two-treatment, two-sequence, two-period crossover study in 26 volunteers. Each treatment was dosed for 3 consecutive days with a washout period of 7 days between dosing periods. Blood samples for pharmacokinetic analysis were taken over the 24 h period following the final dose of omeprazole. RESULTS: Geometric means and ratios were as follows: C(max) was 555 for omeprazole/alginate and 558 for omeprazole alone (ratio 99.55%, 90% confidence interval 82.75-119.75%; AUC(0-t) was 2050 for omeprazole/alginate and 2094 for omeprazole alone (ratio 97.90%, 90% confidence interval 87.83-109.12%); AUC(0-a) was 2247 for omeprazole/alginate and 2231 for omeprazole alone (ratio 100.74%, 90% confidence interval 90.05-112.70%). Mean values for T(max), K(el) and T(1/2) were also similar for the two treatment regimens. INTERPRETATION & CONCLUSION: As the 90 per cent confidence intervals for the geometric mean ratios for C(max), AUC(0-t), and AUC(0-alpha) are all contained within the bioequivalence interval of 80-125 per cent, it can be concluded that the administration of this liquid alginate suspension does not affect the pharmacokinetic profile of omeprazole.

Characterisation of adherens and tight junctional molecules in normal animal larynx; determining a suitable model for studying molecular abnormalities in human laryngopharyngeal reflux.

BACKGROUND: The disruption of intercellular junctions in the larynx is a pathological feature of laryngopharyngeal reflux (LPR). Good experimental models are necessary to gain greater insight into the molecular mechanisms and alterations that result from abnormal exposure of the laryngeal epithelium to acid refluxate. AIMS: To characterise laryngeal tissues from different species to determine the most suitable for use in experimental studies of LPR. METHODS: Human and non-human laryngeal tissues (mouse, rat, guinea pig, porcine, and rabbit) were studied. Histological characterisation was performed by light microscopy. The expression and subcellular localisation of adherens junctional molecules (E-cadherin and beta catenin) was evaluated by immunohistochemistry, and tight junction molecules (occludin and zonula occludens 1 (ZO-1)) by western blotting. The ultrastructural features of porcine and human tissue were assessed by electron microscopy. RESULTS: Porcine tissue revealed both respiratory-type and stratified squamous epithelium, as seen in the human larynx. The expression and subcellular localisation of the E-cadherin-catenin complex was detected in all species except mouse and rat. The pattern of ZO-1 and occludin expression was preserved in all species. CONCLUSION: The expression of intercellular junctional complexes in porcine epithelium is similar to that seen in humans. These results confirm the suitability of these species to study molecular mechanisms of LPR in an experimental system.

Alginate rafts and their characterisation.

Alginate/antacid anti-reflux preparations are designed to provide symptom relief by forming a physical barrier on top of the stomach contents in the form of a neutral floating gel or raft. This study tested the in vitro effectiveness of a range of liquid products in forming rafts that were cohesive, buoyant, voluminous, resistant to reflux and durable under conditions of movement (resilient). The products tested had a wide range of acid neutralising capacities (ANCs). It was found that products with a high ANC and no calcium ion source formed rafts of low strength, weight and volume, which appeared more as floating precipitates than coherent gels. Products with a high ANC and a calcium ion source formed medium strength, weight and volume rafts. Products with a low ANC formed strong coherent rafts with medium to large weight and volume, and those with low ANC and a calcium ion source formed the strongest rafts. Products with stronger rafts were found to be more resilient and more resistant to reflux in an in vitro reflux model. Significant overall differences in raft buoyancy were found between products forming coherent rafts but these could not be related to the product formulation or amount of available carbon dioxide.

Laxative use and its relationship with straining in a London elderly population: free-living versus institutionalised.

BACKGROUND: The diagnosis of functional constipation according to Rome II criteria includes assessment of straining. However the prevalence in older adults is unknown. Moreover, laxative use increases with age, especially in the elderly. AIMS: to assess the prevalence of straining and its association with laxative use in free-living (FL) and institutionalised (INS) older adults. METHODS: 50 FL (mean age 74 years, 42% male) and 42 INS subjects (mean age 84 years, 36% male) were recruited. Straining to start and to finish defecation were prospectively recorded by subjects for 7 consecutive days in a bowel habit diary. Concurrently, the subjects recorded any laxative use during the 7 days study. Statistical analyses were performed using the Chi-square statistic. RESULTS: 20% of FL and 65% of INS subjects recorded taking laxatives during the study week. Of the 40 FL subjects not taking laxatives, 30 had to strain to start on 25% or less of occasions and 36 had to strain to finish on 25% or less of occasions (chi(2) = 7.2; p = 0.012 and chi(2) = 5.4; p = 0.041, respectively). In the INS group, although 64% of subjects taking laxatives had to strain on more than 25% of occasions, the Chi-square test was not statistically significant. CONCLUSIONS: From our results, it seems that laxatives were used appropriately in the FL, with the majority of those taking laxatives having to strain to start on more than 25% of occasions.

Straining at stool and stool frequency in free-living and institutionalised older adults.

BACKGROUND: The diagnosis of functional constipation according to Rome II criteria includes assessment of straining. However the prevalence in older adults is unknown. AIMS: To assess the prevalence of straining and its association with stool frequency in free-living (FL) and institutionalised (INS) older adults. METHODS: 50 FL subjects (mean age 74 years, range (65-97), 42% male) and 42 INS subjects (mean age 84 years, range (69-101) 36% male) were recruited. Stool frequency and straining to start and to finish were prospectively recorded by subjects for 7 consecutive days in a bowel habit diary. Statistical analyses were performed using the Chi-square or the Pearson correlation coefficient as appropriate. RESULTS: The mean stool frequency (n/week) was significantly higher (p <0.001) in the FL group compared with the INS group (11.7 and 4.9 respectively). The percentage of subjects experiencing straining to start on more than 25% of occasions was significantly lower in the FL compared with the INS group (34% and 64% respectively, chi2 = 8.4, p = 0.004, df = 1). The percentage of subjects experiencing straining to finish on more than 25% of occasions was significantly lower in the FL compared with the INS group (16% and 41% respectively, chi2 = 6.9, p = 0.009, df = 1). CONCLUSIONS: FL subjects had significantly higher stool frequency and had to strain passing a stool (to start and to finish) less often than their INS counterparts. Moreover, straining to start was experienced more often than straining to finish in both groups.

The effect of omeprazole pre-treatment on rafts formed by reflux suppressant tablets containing alginate.

Alginate-based reflux suppressant preparations provide symptom relief by forming a physical barrier on top of the stomach contents in the form of a neutral floating gel or raft. This study investigated whether reduced acidity in the stomach brought about by omeprazole pre-treatment affected the formation and gastric residence time of alginate rafts. It was a balanced, cross-over study in 12 healthy non-patient volunteers following a single dose of two indium-111-labelled alginate tablets in the presence or absence of 3 days' pre-treatment with omeprazole. Raft formation and gastric residence, in the presence of a technetium-99m-labelled meal, were assessed by gamma scintigraphy for 3 h after alginate tablet administration. The relative raft-forming ability of alginate tablets after omeprazole compared with alginate tablets alone was 0.950 with 95% confidence intervals of 0.882 and 1.018. Pre-treatment and co-administration with omeprazole has no significant effect on the raft-forming ability of alginate tablets.

Neuropharmacological studies in rodents on the action of RX 781094, a new selective alpha 2-adrenoceptor antagonist.

Several neuropharmacological effects of RX 781094, a new selective alpha 2-adrenoceptor antagonist, have been investigated in rodents. In rats, RX 781094 (0.1-1.0 mg kg-1, i.v.) produced a rapid dose-related reversal of cortical EEG synchronisation and behavioural sedation, induced by clonidine or the more selective alpha 2-adrenoceptor agonist, guanoxabenz. The alpha 2-adrenoceptor antagonists yohimbine and mianserin were also effective in blocking guanoxabenz-induced EEG synchronisation but had a lower potency than did RX 781094. In specificity experiments, RX 781094 (1.0 mg kg-1, i.v.) failed to antagonise the EEG synchronisation and pronounced behavioural sedation induced by the CNS depressant sodium pentobarbitone (15 mg kg-1, i.v.). In mice, pretreatment (i.v. or p.o.) with RX 781094 inhibited in a dose-dependent way both guanoxabenz-induced behavioural hypoactivity and clonidine-induced hypothermia. By itself, RX 781094 had no effect on the temperature of normal mice. In sleep-waking studies in rats, RX 781094 (0.1 and 1.0 mg kg-1, i.v.) had no measurable stimulant or depressant effect on the CNS, in contrast to (+)-amphetamine (1.0 mg kg-1, i.v.) which elicited marked CNS stimulation. These results support the conclusion that RX 781094 is a potent antagonist at central alpha 2-adrenoceptors.

Analeptic effects of centrally injected TRH and analogues of TRH in the pentobarbitone-anaesthetized rat.

The effect of intracerebral injection of TRH and several biologically stable TRH analogues in the pentobarbitone anaesthetized rat was examined. Bilateral injection of TRH (5.0 micrograms total dose) and the analogues RX 77368 (0.01-1.0 microgram), CG 3509 (0.1-1.0 microgram), DN-1417 (1.0 microgram) and MK-771 (1.0 microgram) into the nucleus accumbens reduced the pentobarbitone-induced sleeping time. The TRH metabolite DKP (5 micrograms) had no effect on the sleeping time following intra-accumbens injection. Intra-septal injection of TRH (1.0-5.0 micrograms), RX 77368 (0.1-1.0 microgram) and CG 3509 (0.1-1.0 microgram) also reversed the pentobarbitone-induced sleeping time. In contrast, TRH (5 micrograms) injected into the striatum had no effect on the pentobarbitone-induced sleeping time, and CG 3509 (0.1 microgram) and RX 77368 (0.1 microgram) had weaker effects following intrastriatal injection compared to injection of these analogues into the nucleus accumbens and septum. Measurements of core temperature and respiration rate in rats following intra-accumbens or septal injection of TRH, CG 3509 and RX 77368 showed these peptides to reverse pentobarbitone-induced hypothermia and stimulate respiration rate. However, while intrastriatal injections of CG 3509 and RX 77368 caused an increase in respiration rate they had no effect on core temperature. These results suggest a close association between peptide-induced respiratory stimulation and reversal of pentobarbitone-induced anaesthesia. Since intra-accumbens and septal injection of dopamine (20-100 micrograms) failed to reverse anaesthesia, it is unlikely that the peptide-induced responses are mediated via dopamine release.

The effect of alpha 2-adrenoceptor agonists on the acid secretory responses of rat isolated gastric mucosa to electrical field stimulation.

The effects of clonidine, UK-14,304, noradrenaline, para-aminoclonidine and phenylephrine were examined on the acid secretory response of the rat isolated gastric mucosa preparation to electrical field stimulation. Clonidine, UK-14,304, noradrenaline and para-aminoclonidine but not phenylephrine (10 microM) reduced the response of the gastric mucosa stimulated at 2.5 Hz; gastric mucosae stimulated at higher frequencies were insensitive to the action of these alpha 2-adrenoceptor agonists. The inhibitory effect of the selective alpha 2-adrenoceptor agonist UK-14,304 was antagonized by idazoxan but not by prazosin. These findings indicate that clonidine and other alpha 2-adrenoceptor agents inhibit the acid secretory response of the rat gastric mucosa to electrical field stimulation by an action at alpha 2-adrenoceptors, which are probably located on cholinergic nerve terminals.

Effects of idazoxan on catecholamine systems in rat brain.

Experiments have been performed to assess the potency of idazoxan (RX 781094) at alpha and beta-adrenoceptors and dopamine receptors and on catecholamine uptake processes in rat brain. The effects of idazoxan on the turnover rates of noradrenaline and dopamine have been determined. Radioligand binding studies with cerebral cortex membranes have demonstrated that idazoxan exhibits 46-fold selectivity for alpha 2-adrenoceptors labelled by (3H)-idazoxan (Mean Ki +/- S.E.M. = 3.1 +/- 0.4 nM) compared with alpha 1-adrenoceptors labelled by (3H)-prazosin (Mean Ki +/- S.E.M. = 142 +/- 27 nM). Under the same conditions, yohimbine showed 6-fold selectivity for alpha 2-adrenoceptors. Idazoxan had low affinity for beta-adrenoceptors labelled by (3H)-dihydroalprenolol (IC50 value greater than 10 microM), for dopamine receptors labelled by (3H)-domperidone (IC50 value greater than 20 microM), for the (3H)-noradrenaline uptake site in rat hypothalamus (IC50 = 31 microM) and for the (3H)-dopamine uptake site in rat striatum (IC50 value approximately 800 microM). In rats treated with alpha-methyl-p-tyrosine, idazoxan (10-80 mg/kg, po) produced a marked increase (63% at 10, 217% at 20 mg/kg, po) in the apparent rate of turnover of noradrenaline in rat cortex/striatum, without affecting the rate of turnover of dopamine. This was in contrast to yohimbine (5-20 mg/kg, po) which increased the turnover rates of both catecholamines. In the absence of alpha-methyl-p-tyrosine, idazoxan (5-40 mg/kg, po) produced a dose related increase in the MHPG concentration and a small (20-30%) reduction in the steady state concentration of NA; the duration of the reduction was dose-related. DA steady state concentrations were unaffected. Idazoxan is a new selective alpha 2-adrenoceptor antagonist which should prove a valuable investigative tool in neurochemical studies and which may be a useful clinical agent in the management of the affective disorders.

The effect of chitin and chitosan on the proliferation of human skin fibroblasts and keratinocytes in vitro.

The effects of chitin [(1 --> 4)-2-acetamido-2-deoxy-beta-D-glucan] and its partially deacetylated derivatives, chitosans, on the proliferation of human dermal fibroblasts and keratinocytes were examined in vitro. Chitosans with relatively high degrees of deacetylation strongly stimulated fibroblast proliferation while samples with lower levels of deacetylation showed less activity. Fraction, CL313A, a shorter chain length, 89% deacetylated chitosan chloride was further evaluated using cultures of fibroblasts derived from a range of human donors. Some fibroblast cultures produced a positive mitogenic response to CL313A treatment with proliferation rates being increased by approximately 50% over the control level at an initial concentration of 50 microg/ml, whilst others showed no stimulation of proliferation or even a slight inhibition (< 10%). The stimulatory effect on fibroblast proliferation required the presence of serum in the culture medium suggesting that the chitosan may be interacting with growth factors present in the serum and potentiating their effect. In contrast to the stimulatory effects on fibroblasts, fraction CL313A inhibited human keratinocyte mitogenesis with up to 40% inhibition of proliferation being observed at 50 microg/ml. In general highly deacetylated chitosans were more active than those with a lower degree of deacetylation. These data demonstrate that highly deacetylated chitosans can modulate human skin cell mitogenesis in vitro. Analysis of their effects on cells in culture may be useful as a screen for their potential activity in vivo as wound healing agents, although in the case of fibroblasts it is important to select appropriate strains of cells for use in the screen.

The gastrointestinal transit profile of 14C-labelled poly(acrylic acids): an in vivo study.

The gastrointestinal distribution profiles for three 14C-labelled poly(acrylic acid)s of different average molecular weights and degrees of cross-linking have been established using the rat model. Despite initial differences in transit times and retention characteristics, these structural features were found to be of little influence to the overall gastrointestinal transit of the materials under consideration. No evidence for the systemic absorption of any of the polymers could be identified.

Effect of ispaghula husk on the faecal output of bile acids in healthy volunteers.

Faecal bile acids are associated with both colorectal cancer and serum cholesterol levels. We investigate whether dosing with ispaghula husk affects the faecal bile acid weights and concentrations in healthy adults. Sixteen healthy volunteers consumed 7.0 g/day ispaghula husk, containing 5.88 g/day Englyst-determinable dietary fibre, for the middle 8 weeks of a 12-week period. Stool samples were collected, analysed for faecal bile acids and their form and dry weight determined. Correlations between the faecal bile acids, the stool parameters and the dietary intake were tested. Ispaghula husk treatment significantly lowers faecal lithocholic and isolithocholic acids and the weighted ratio of lithocholic acids to deoxycholic acid. These effects revert towards their initial states at the end of the treatment period. These changes in the faecal bile acid profiles indicate a reduction in the hydrophobicity of the bile acids in the enterohepatic circulation.

Determination of the antibacterial efficacy of several antiseptics tested on skin by an 'ex-vivo' test.

There are many skin antiseptics commercially available. Although their antibacterial activity has often been well studied, their potential effectiveness on skin remains poorly documented. To date, in-vivo protocols designed for the testing of the antimicrobial efficacy of antiseptics cannot use, for ethical reasons, pathogenic bacteria or new formulations whose toxicity in human subjects is unknown. An 'ex-vivo' test was recently developed to overcome these problems. Freshly excised human skin from abdominal or breast reduction was placed in a diffusion cell containing a maintenance medium in the recipient compartment. A bacterial inoculum was then applied to the stratum corneum and, after a drying step, antiseptic formulations were evaluated for their antimicrobial activity. Several micro-organisms were investigated: - Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Enterococcus faecalis, vancomycin-resistant Ent. faecium (VRE), S. epidermidis, Pseudomonas aeruginosa and Escherichia coli--with several biocides--para-chloro-meta-xylenol (PCMX, active compound of Dettol), povidone iodine, triclosan (in isopropanol) and chlorhexidine. Results from the ex-vivo test were compared with results obtained in suspension and glass-carrier tests. The bactericidal activity of the biocides depended upon the test performed and results were generally significantly different from one method to the other. All biocides tested in the suspension test achieved >4 log10 reduction in viable bacterial concentrations, apart from povidone iodine tested against Ent. faecalis and VRE. The antibacterial activity of biocides tested in the glass-carrier test was significantly lower than in the suspension test, with the exception of triclosan in isopropanol, which was as effective in both suspension and glass-carrier test. In the ex-vivo test, triclosan in isopropanol achieved a log10 reduction in viable bacterial concentration of 1.105-1.771 (with the exception of P. aeruginosa with 0.758 log10 reduction). PCMX, povidone iodine and chlorhexidine achieved log10 reductions in viable bacterial concentration of 0.303-0.901. Chlorhexidine tested against P. aeruginosa produced a 1.94 log10 reduction in concentration. These results confirm previous observations about the need for testing the antimicrobial activity of antiseptics on skin surface to determine their in-situ efficacy and encourage further the use of the ex-vivo protocol.

Thyrotropin-releasing hormone (TRH) analogues show enhanced CNS selectivity because of increased biological stability.

TRH exerts both endocrinological and neuropharmacological actions. Two analogues of TRH, Pyr-His-Mep . NH2 (L-trans-3-methylprolineamide) and Pyr-His-Dmp . NH2 (L-3,3-dimethylprolineamide) have been examined for their neuropharmacological and endocrinological effects. Comparisons of their ability to provoke hyperthermia in rabbits demonstrated that both analogues were more potent than TRH, but like the parent peptide had only a limited ability to cross the blood brain barrier. This conclusion was confirmed by whole body autoradiographical studies. In contrast both analogues had a similar potency to TRH with respect to the ability to provoke TSH release. It is concluded that the increased potency in neuropharmacological tests results from enhanced bioavailability to CNS sites and that a similar rationale can be used to explain the CNS selectively claimed in the literature for other analogues of TRH.