Botulinum toxin blocks mast cells and prevents rosacea like inflammation

Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.

Serum leptin concentrations in pre- and postmenopausal women on sex hormone therapy.

AIM: The aim of the present study was to investigate the influence of endogenous estradiol and estrogen and estrogen-progestin therapies on concentration in pre- and postmenopausal women. MATERIALS AND METHODS: The study groups consisted of 26 women with surgical menopause (mean+/-standard deviation (SD): age 51.8+/-2.6 years, body mass index (BMI) 26.45+/-4.56 kg/m(2)), 54 with natural menopause (mean+/-SD: age 50.5+/-3.0 years, BMI 25.75+/-4.09 kg/m(2)) and 40 premenopausal controls (mean+/-SD: age 48.3+/-2.3 years, BMI 26.23+/-4.12 kg/m(2)). The group with surgical menopause received estradiol transdermally (50 microg/day) and those with natural menopause received additionally medroxyprogesterone acetate (5 mg/day) for the last 12 days of the cycle. Before and after 4 months of therapy, body weight, waist and hip circumferences and blood pressure were measured, and BMI and waist-to-hip ratio (WHR) were calculated. Serum leptin, follicle-stimulating hormone (FSH), estradiol (E(2)), testosterone, prolactin and dehydroepiandrosterone sulfate (DHEAS) were measured prior to and after treatment. RESULTS: Leptin concentrations did not differ statistically among the groups. No correlations between leptin and E(2), FSH, prolactin, testosterone and DHEAS concentrations were found in any of the groups before and after treatment. Leptin level correlated positively with body mass, BMI and hip and waist circumferences in all groups. There were no correlations between leptin and WHR in the pre- and postmenopausal groups. In the premenopausal group and in some postmenopausal groups, serum leptin level correlated with blood pressure. CONCLUSIONS: Endogenous E(2) and androgens in premenopausal women and estrogen and estrogen-progestin therapies in postmenopausal subjects do not influence serum leptin concentrations. Leptin level is related to body mass and BMI, but not to sex hormone status. The distribution of adipose tissue and the type of obesity (android or gynoid) have no influence on serum leptin concentration. The correlation between serum leptin level and blood pressure requires further investigation.     

The neutrophil oxidative burst in diarrhoea – associated haemolytic uraemic syndrome

. Neutrophil-mediated tissue damage has been implicated in the pathogenesis of diarrhoea-associated haemolytic uraemic syndrome (D+ HUS). This study evaluates priming and activation of the neutrophil oxidative burst in D+ HUS using chemiluminescent techniques. Peripheral blood neutrophils from 11 children with acute D+ HUS were examined. No difference was found in the oxidative burst of neutrophils from patients and controls. Serum elastase levels were measured in 8 patients and found to be significantly elevated. Although elastase results suggest neutrophil activation, chemiluminescence studies do not confirm this in the peripheral blood neutrophil. This does not support a significant role for circulating agents in priming and activating the peripheral blood neutrophil. Received August 17, 1995; received in revised form and accepted November 27, 1995     

The effects of dietary modification as denned by NACNE on the eating habits of 28 people

Twenty-eight members of the general public, with little nutritional knowledge and no previous commitment to dietary change, completed 7-day-weighed dietary diaries. They then attempted to change their diets, where appropriate, in line with current nutritional guidelines.
The panel achieved changes in diet that were consistent with the recent recommendations but several problems arose. In particular, although fat levels were reduced, energy levels fell and fibre goals were not reached; in addition, certain of the initial vitamin and mineral intakes gave cause for concern. These results emphasize the importance of giving advice not only about foods that might be reduced in the diet, but also about food that might be used as alternatives. They also illustrate the difficulty of persuading people to make radical changes to their eating habits even when given personal advice from a nutritionist.
The panel was small and not necessarily representative, but the results illustrate the need for more dietary analysis studies. It is not enough simply to formulate appropriate guidelines from a nutritional point of view; it is also important to ensure that the public understands them and that people make sensible decisions about their diet.     

A case of unilateral opercular syndrome associated with a subcortical lesion

Summary A patient who developed a unilateral opercular syndrome following a cerebrovascular accident is described. Computed tomography showed that the lesion did not affect the opercular cortex, but involved deep white matter and the head of the caudate nucleus of the left hemisphere. Persistent hypophonia and transient aphasia were associated. Comparison with previous cases is discussed.     

Frequency of and risk factors for allergy in primary school children: results of a population survey

During May 1986, a survey to assess the frequency of allergic disorders was conducted among primary school children of Alghero, Sardinia, using a structured self-administered questionnaire. The following problems were investigated: allergic conjunctivitis, asthma, wheezing, allergic rhinitis, urticaria and eczema. Of the original 1823 questionnaires distributed, 1961 (92.8%) were completed by parents and returned. Overall, 238 children (14.1%) were reported to have shown at least one episode of one or more of the above and were regarded as 'allergic'. Among the potential risk factors investigated, statistically significant differences (P less than 0.05) between allergic and non-allergic children were only found for history of allergy in at least one parent (odds ratio, OR = 2.2) and exposure to passive smoking (OR = 1.4).     

Simultaneous assessment of blood flow in UVB-inflamed human skin by laser Doppler flowmetry and the 133-xenon washout technique.

The purpose of the study was to compare skin blood flow by laser Doppler flowmetry (LDF) and the 133-Xenon washout technique in UVB-inflamed human skin. Six healthy subjects participated in the study. Forearm skin blood flow was measured prior to irradiation and then 8, 24, 48 and 72 h after the exposure to twice the minimal erythema dose of UVB. Baseline blood flow as measured by the 133-Xenon washout method was 5.2 (range 3.0 to 10.4) ml/100g/min and LDF flux was 3.1 (range 2.7 to 5.7) arbitrary units. Following irradiation, maximum blood flow increase as evaluated by the 133-Xenon washout was 10.8 (95% confidence interval 3.7 to 11.3) times baseline blood flow, corresponding to an absolute blood flow of 47.5 (range 33.8 to 56.3) ml/100g/min. Maximum increase after induction of inflammation as assessed by LDF was 34.6 (95% confidence interval 24.6 to 56.5) times baseline flux. The two methods showed comparable time courses in all subjects. A significant correlation between the two methods was found, Spearman's rho = 0.54, p = 0.006. The relative LDF blood flow increase was 4.2-fold (95% confidence interval 2.7 to 5.0) greater than the increase measured by the 133-Xenon washout method. These results are at variance with previous comparative studies of the two methods. Some explanations are discussed.     

Thyrotrophin-Releasing Hormone Raises Cytosolic Free Calcium Concentration in Human Adenomatous Somatotrophs and Corticotrophs; Comparison with in vivo Responsiveness to Thyrotrophin-Releasing Hormone in Patients with Acromegaly or Cushing's Disease

The effect of thyrotrophin-releasing hormone (TRH) on intracellular free Ca²⁺ concentration, [Ca²⁺)i, was investigated with the fluorescent dye fura-2 in cell suspensions obtained from 13 human growth hormone-secreting adenomas and 6 adrenocorticotrophin-secreting adenomas. Preoperatively, 9 out of 13 acromegalic patients showed a positive growth hormone response to TRH administration while none of the 6 patients with Cushing's disease had a plasma adrenocorticotrophin increase after TRH injection. In all the growth hormone-secreting adenomas the addition of TRH (100 nM) caused a significant rise in [Ca²⁺]i (from a resting level of 133±40 (±SD) to a value of 284±119 nM at 100 nM TRH, n = 42; P<0.001). The transient induced by TRH was found to have a dual origin, one due to Ca²⁺ mobilization from intracellular stores which was maintained in presence of EGTA (3mM) and verapamil (10 μM) and a plateau phase due to Ca²⁺ influx from the extracellular media. Somatostatin (0.1 μM) lowered both resting [Ca²⁺]i and TRH-induced transients. The effect of gonadotrophin-releasing hormone on [Ca²⁺]i was evaluated on cell suspensions obtained from 6 growth hormone-secreting adenomas. Gonadotrophin-releasing hormone (100 nM) caused a marked rise in [Ca²⁺]i (from 179±25 to 283±15nM) on the cell suspension obtained from the only in vivo responsive adenoma while it was ineffective in the remaining 5. Although TRH was ineffective in modifying plasma adrenocorticotrophin levels in all patients with Cushing's disease, in 5 out of 6 tumors the addition of 100 nM TRH caused a significant rise in [Ca²⁺]i (from 102.5 ± 36 to 163±66 nM, n = 22; P < 0.005). However, the effect of TRH on [Ca²⁺]i was significantly lower than that caused by arginine vasopressin, a physiological stimulator of adrenocorticotrophin release ([Ca²⁺]i values; 145±78 nM at 100 nM TRH versus 300±140 at 10 nM arginine vasopressin, n = 15; P<0.05). Moreover, the effect of arginine vasopressin on [Ca²⁺]i was detectable at concentrations as low as 0.1 nM while TRH was effective at concentrations higher than 1 nM. By contrast, gonadotrophin-releasing hormone was ineffective in increasing [Ca²]i in all the adrenocorticotrophin-secreting adenomas studied. Collectively, these data indicate that sensitivity to TRH is present in almost all the growth hormone- and adrenocorticotrophin-secreting adenomas independently of the responsiveness of the individual patients to the peptide.