Emollient structure and chemical functionality effects on the biomechanical function of human stratum corneum.

OBJECTIVE: Cosmetic emollients are widely used in skincare formulations due to their ability to 'soften' the skin and modulate formulation spreadability. Though emollients are commonly used, little is known about their effects on the biomechanical barrier properties of human stratum corneum (SC), which play a critical role in consumer perception of formulation efficacy. Accordingly, our objective was to provide new insights with a study involving fourteen cosmetic emollient molecules with widely varying structures, molecular weights, SC diffusivities, topological polar surface areas (TPSAs), viscosities and chemical functionalities. METHODS: Mechanical stress in the SC was measured in vitro using a substrate curvature measurement technique. Stress development due to SC drying was measured before and after topical treatment with cosmetic emollients. Emollient diffusivity and alterations to lipid content in SC after treatment were measured via ATR-FTIR spectroscopy. The maximum penetration volume of emollient in SC was characterized to elucidate mechanisms underlying emollient effects on stress. RESULTS: The application of all cosmetic emollients caused a reduction in SC mechanical stress under dehydrating conditions, and a linear correlation was discovered between emollient penetration volume and the degree of stress reduction. These molecules also induced increases in stress equilibration rate, signalling changes to SC transport kinetics. Stress equilibration rate increases linearly correlated with decreasing intensity of the νCH2 band, indicating a previously unknown interaction between cosmetic emollients and SC lipids. Stress and penetration volume results were rationalized in terms of a multi-parameter model including emollient molecular weight, diffusivity, TPSA and viscosity. CONCLUSION: We provide a new rational basis for understanding the effects of cosmetic emollient choice on biomechanical properties affecting SC barrier function and consumer perception. We demonstrate for the first time that emollients very likely reduce SC mechanical stress through their ability to take up volume when penetrating the SC, and how molecular weight, SC diffusivity, TPSA and viscosity are predictive of this ability. As cosmetic formulations continue to evolve to meet the needs of customers, emollient molecules can be selected that not only contribute to formulation texture and/or spreadability but that also leverage this novel connection between emollient penetration and SC biomechanics.

OBJECTIF: Les émollients cosmétiques sont largement utilisés dans les formulations de soins de la peau en raison de leur capacité à «adoucir¼ la peau et à moduler la capacité d'étalement de la formulation. Bien que les émollients soient couramment utilisés, on en sait peu sur leurs effets sur les propriétés de barrière biomécanique de la couche cornée humaine (SC), qui jouent un rôle essentiel dans la perception par les consommateurs de l'efficacité de la formulation. En conséquence, notre objectif était de fournir de nouvelles perspectives avec une étude impliquant quatorze molécules émollientes cosmétiques avec des structures, des poids moléculaires, des diffusivités SC, des surfaces polaires topologiques (TPSA), des viscosités et des fonctionnalités chimiques très variables. MÉTHODES: La contrainte mécanique dans le SC a été mesurée in vitro en utilisant une technique de mesure de la courbure du substrat. Le développement du stress dû au séchage SC a été mesuré avant et après un traitement topique avec des émollients cosmétiques. La diffusivité émolliente et les altérations de la teneur en lipides dans la SC après le traitement ont été mesurées par spectroscopie ATR-FTIR. Le volume de pénétration maximal de l'émollient dans SC a été caractérisé pour élucider les mécanismes sous-jacents aux effets émollients sur le stress. RÉSULTATS: L'application de tous les émollients cosmétiques a entraîné une réduction de la contrainte mécanique SC dans des conditions de déshydratation, et une corrélation linéaire a été découverte entre le volume de pénétration de l'émollient et le degré de réduction de la contrainte. Ces molécules ont également induit des augmentations du taux d'équilibrage des contraintes, signalant des changements dans la cinétique de transport SC. Le taux d'équilibrage des contraintes augmente linéairement en corrélation avec la diminution de l'intensité de la bande νCH2 , indiquant une interaction jusque-là inconnue entre les émollients cosmétiques et les lipides SC. Les résultats du stress et du volume de pénétration ont été rationalisés en termes d'un modèle multi-paramètres comprenant le poids moléculaire émollient, la diffusivité, le TPSA et la viscosité. CONCLUSION: Nous fournissons une nouvelle base rationnelle pour comprendre les effets du choix des émollients cosmétiques sur les propriétés biomécaniques affectant la fonction de barrière SC et la perception du consommateur. Nous démontrons pour la première fois que les émollients réduisent très probablement la contrainte mécanique SC grâce à leur capacité à prendre du volume lors de la pénétration du SC, et comment le poids moléculaire, la diffusivité SC, le TPSA et la viscosité sont prédictifs de cette capacité. Alors que les formulations cosmétiques continuent d'évoluer pour répondre aux besoins des clients, des molécules émollientes peuvent être sélectionnées qui contribuent non seulement à la texture et / ou à l'étalement de la formulation, mais qui exploitent également cette nouvelle connexion entre la pénétration des émollients et la biomécanique SC.

The disulfonic stilbene DIDS and the marine poison maitotoxin activate the same two types of endogenous cation conductance in the cell membrane of Xenopus laevis oocytes.

In the present experiments we exposed the intra- or extracellular surface of excised giant membrane patches of Xenopus laevis oocytes bathed in 140 mmol/l Na-aspartate solution to the anion transport inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS, 250 micromol/l). We observed that DIDS activated at least two cation conductances: (1) a non-selective cation (NSC) conductance that was mediated by channels of approximately 27 pS and resembled the stretch-activated cation conductance that has been observed in the oocyte cell membrane previously, and (2) a Na+-selective conductance, the single-channel events of which could not be resolved and which resembled the depolarization-induced Na+ conductance that has also been observed in the oocyte cell membrane previously. Both conductances were blocked by 1 mmol/l amiloride from the intra- and extracellular surfaces but inhibition of the NSC conductance by extracellular amiloride was less pronounced. Both conductances activated only slowly with a delay of 15-60 s after application of DIDS and remained active even after DIDS was washed off. This suggests that DIDS caused the exocytosis of preformed channels and this interpretation was supported by our additional observation that extracellular application of maitotoxin (MTX) mimicked the effects of DIDS. MTX is a marine toxin that has recently been reported to induce exocytosis in Xenopus laevis oocytes. The fact that DIDS and MTX each carry two sulfonyl groups suggests that they act on the same positively charged binding sites of an exocytosis-inducing protein. Our observations demonstrate that using DIDS to inhibit heterologously expressed anion transporters in the cell membrane of Xenopus laevis oocytes may compromise proper determination of the transporter currents. This effect can be prevented if the DIDS-activated endogenous cation conductances are suppressed by application of amiloride to the cytoplasmic surface of the cell membrane.

Mechanism of shrinkage activation of nonselective cation channels in M-1 mouse cortical collecting duct cells.

It has previously been shown that osmotic cell shrinkage activates a nonselective cation (NSC) channel in M-1 mouse cortical collecting duct cells [54] and in a variety of other cell types [20]. In the present study we further characterized the shrinkage-activated NSC channel in M-1 cells and its mechanism of activation using whole-cell current recordings. Osmotic cell shrinkage induced by addition of 100 mm sucrose to the bath solution caused a 20-fold increase in whole-cell inward currents from -10.8 +/- 1.5 pA to -211 +/- 10.2 pA (n = 103). A similar response was observed when cell shrinkage was elicited using a hypo-osmotic pipette solution. This indicates that cell shrinkage and not extracellular osmolarity per se is the signal for current activation. Cation substitution experiments revealed that the activated channels discriminate poorly between monovalent cations with a selectivity sequence NH(4) (1.2) > or = Na(+) (1) approximately K(+) (0.9) approximately Li(+) (0.9). In contrast there was no measurable permeability for Ca(2+) or Ba(2+) and the cation-to-anion permeability ratio was about 14. The DPC-derivatives flufenamic acid, 4-methyl-DPC and DCDPC were the most effective blockers followed by LOE 908, while amiloride and bumetanide were ineffective. The putative channel activator maitotoxin had no effect. Current activation was dependent upon the presence of intracellular ATP and Mg(2+) and was inhibited by staurosporine (1 microm) and calphostin C (1 microm). Moreover, cytochalasin D (10 microm) and taxol (2 microm) reduced the current response to cell shrinkage. These findings suggest that the activation mechanism of the shrinkage-activated NSC channel involves protein kinase mediated phosphorylation steps and cytoskeletal elements.

Validation of a high-performance liquid chromatography assay for quantification of caffeine and paraxanthine in human serum in the context of CYP1A2 phenotyping.

In this study the validation of a reversed-phase high-performance liquid chromatography (HPLC) method, with UV-detection, for both caffeine and paraxanthine in human serum is described. This method is feasible for cytochrome P450 1A2 (CYP1A2) phenotyping, according to the results of a pilot study. With this HPLC method caffeine and paraxanthine can be determined selectively and specifically. In the expected concentration range, caffeine recoveries were 98-108% (within-run variation 4.0-6.4%, between-run variation 6.4-8.8%), paraxanthine recoveries were 96.6-97.5% (within-run variation 5.0-7.2%, between-run variation 7.2-10.8%). The limits of detection for caffeine and paraxanthine using this HPLC system were 0.3 and 0.1 mg/L, respectively. Linear calibration curves for both caffeine and paraxanthine were obtained in the concentration range 0.5-30 mg/L (r > 0.9999. Serum samples were stable for a week, when stored at -20 and +4 degrees C.

Nifedipine-induced gingival enlargement around dental implants: a clinical report.

Calcium channel-blocking agents are used extensively for the management of cardiovascular conditions, including angina pectoris, coronary artery spasm, cardiac arrhythmias, and hypertension. Gingival overgrowth around natural teeth has been previously reported in the literature with patients taking calcium channel-blocking agents. This clinical report describes hyperplasia of tissues around titanium dental implants in a patient taking Nifedipine along with the multiphasic approach to treating this medication-induced hyperplasia of the peri-implant tissues.

Determinants of low systemic vascular resistance during cardiopulmonary bypass.

Although low systemic vascular resistance occurs during normothermic and hypothermic cardiopulmonary bypass, the determinants of depressed systemic vascular resistance and its effect on outcomes are unknown. To assess the predictors and clinical effects of low systemic vascular resistance, 555 patients undergoing isolated coronary artery bypass grafting were evaluated prospectively. The extent of low systemic vascular resistance during bypass was estimated by the amount of the vasoconstrictor phenylephrine administered: group 1, 0 to 160 micrograms; group 2, 161 to 800 micrograms; group 3, more than 800 micrograms. Multivariate analysis identified bypass temperature, bypass time, and ventricular function as determinants of low systemic vascular resistance. Patients on normothermic bypass accounted for 65% of the patients in group 3 and only 34% of the patients in group 1 (p < 0.0001). The bypass time was longer in the patients in group 3 (97 +/- 28 minutes) than in the patients in group 1 (89 +/- 24 minutes; p < 0.006). Patients with a preoperative left ventricular ejection fraction of 0.40 or less required less phenylephrine during cardiopulmonary bypass (498 +/- 68 micrograms) than did patients with a fraction exceeding 0.40 (1,087 +/- 88 micrograms; p < 0.001). By multivariate analysis, advanced age and the presence of peripheral vascular disease were found to decrease the likelihood of low systemic vascular resistance during normothermic bypass. Diabetes, the left ventricular ejection fraction, the bypass time, and the total cardioplegia infused were found to influence the likelihood of low systemic vascular resistance during hypothermic bypass. Patients in group 3 had a higher cardiac index and lower-mean arterial pressure and systemic vascular resistance postoperatively. In those patients who received a left internal mammary artery graft, the incidences of the low-output syndrome (group 1, 4.9%; group 3, 2.7%; p = not significant) and myocardial infarction (group 1, 1.4%; group 3, 1.8%; p = not significant) were not influenced by the amount of phenylephrine infused during cardiopulmonary bypass. In those patients who were at high risk of suffering a stroke preoperatively, the hypotension induced by the low systemic vascular resistance and its treatment with phenylephrine was not associated with an increased incidence of stroke (group 1, 5.8%; group 3, 2.8%; p = not significant).

A randomized study of the systemic effects of warm heart surgery.

The technique of warm heart surgery is defined as continuous warm blood cardioplegia and normothermic cardiopulmonary bypass. Although the systemic effects of traditional myocardial protection are well known, the effects of warm heart surgery are not. In a prospective trial, 204 patients undergoing coronary artery bypass grafting were randomized to the warm heart surgery technique (normothermic group) or traditional intermittent cold blood cardioplegia and cardiopulmonary bypass (hypothermic group). The groups had similar heparin sodium requirement, activated clotting times, urine output, hematocrit, and blood product utilization. There were no differences in hemodynamics immediately after cardiopulmonary bypass. The normothermic patients had a higher incidence of spontaneous defibrillation at cross-clamp removal (84%) than the hypothermic patients (33%) (p less than 0.01). An increase in the flow rate of low K+ cardioplegia was necessary to eradicate electrical activity during aortic occlusion more often in the normothermic patients (20%) than in the hypothermic patients (3%) (p less than 0.01). When low K+ cardioplegia was ineffective, high K+ cardioplegia was necessary to eradicate electrical activity in 31% of the normothermic patients compared with 10% of the hypothermic patients (p less than 0.05). The total cardioplegia volume delivered to the normothermic group (4.7 +/- 1.9 L) was higher than that delivered to the hypothermic group (2.6 +/- 0.8 L) (p less than 0.01). Although urine output was similar in both groups, the serum K+ levels were higher in the normothermic group (5.7 +/- 0.8 mmol/L) than in the hypothermic group (5.3 +/- 0.8 mmol/L) (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

The safety of awake tracheal intubation in cervical spine injury.

As a referral centre for cervical spine injuries, we have routinely performed awake tracheal intubation when intubation was indicated. A retrospective case control study was undertaken to review the frequency of neurological deterioration and aspiration associated with our approach. Neurological deterioration was assessed by a change in level of injury or neurological grade at admission and discharge. Four hundred and fifty-four patients with critical cervical spine and/or cord injuries were reviewed over an eight-year period. A case group of 165 patients underwent tracheal intubation awake within two months of injury. A control group of 289 remained unintubated during the same period. A comparison of spinal neurological status between admission and discharge revealed no statistically significant difference in neurological deterioration between the two groups. This occurred despite a greater injury severity score in the case group. No evidence of aspiration during intubation was documented. We conclude that awake tracheal intubation is a safe method of airway management in patients with cervical spine injuries.

Anaesthetic management of acute blunt thoracic trauma.

Sunnybrook Health Science Centre is an adult regional trauma unit serving metropolitan Toronto and environs. We undertook a two-year retrospective review of patients admitted to our institution with blunt thoracic trauma. Three hundred and thirty-three patients with blunt trauma and an injury severity score (ISS) greater than 17 required emergency surgery. Of these, 208 had blunt thoracic injuries while 125 did not have chest injuries. Both groups were similar with respect to age but patients with thoracic trauma had a greater ISS. (P less than 0.05) and greater intraoperative mortality (P less than 0.01). The aetiology of the intraoperative deaths with one exception was exsanguination. Emergency thoracotomy or sternotomy indicated a poor prognosis with a mortality rate of 80%. The most common intraoperative problem was an elevated airway pressure. Awake intubation was undertaken in 77.5% of patients requiring anaesthesia and surgery because of the potentially compromised airways and difficult intubations due to the nature of the associated injuries. Finally, 74% of patients undergoing urgent surgery required mechanical postoperative ventilation. The presence of blunt chest trauma should be considered a marker of the severity of injury sustained by the patient.

Early identification of high-risk patients using the "estimated" injury severity score and age.

A prospective study was undertaken over a 2 1/2 year period (July 1, 1985-December 31, 1987) to determine the value of a prospective anatomical severity score ["Estimated" Injury Severity Score (EISS)], in combination with age, for early risk assessment. Five hundred ninety-two blunt trauma patients were used to develop a predictive model of mortality through a logistic regression. The model was validated using 216 patients; a high degree of agreement (Kappa 0.73) was found. When isolated head injuries were removed from the model and validation groups, the Kappa increased to 0.80. Prospective anatomical scoring in combination with age may help to identify high-risk trauma patients early during their care.

The use of halothane in the treatment of status asthmaticus.

The case is presented of a 39-year-old male in status asthmaticus who failed to respond to conventional therapy, including positive pressure ventilation, and who required halothane anesthesia. The urgent need to reduce his elevated airway pressure and his risk of barotrauma prompted this action. The patient's response was prompt with marked reductions in airway pressure. Discontinuing halothane resulted in rises in airway pressure, necessitating reinstitution of halothane on several occasions. The mechanism of the bronchodilating action of halothane, as well as potential interactions with other pharmacotherapy and precautions for its use, are described.

The Prentif contraceptive cervical cap: acceptability aspects and their implications for future cap design.

Patients in a private gynecological practice were offered the Prentif contraceptive cervical cap. The first 413 acceptors were sent a questionnaire covering in detail many of the aspects of their experience. The 371 responses contained a wealth of information concerned with safety, effectiveness and acceptability. Safety and effectiveness are dealt with in the companion article preceding, while the less serious risk factors that reduce the acceptability of the Prentif cap are presented and discussed herein. In order of descending frequency, these factors include: odor; difficulty removing; discomfort to partner; difficulty inserting; dislike of spermicide; discomfort to self; urinary discomforts; vaginal infections; vaginal discharge; and vaginal itching. The most attractive features of the cap, as compared with the diaphragm, were: increased convenience; greater safety; less interference with spontaneity; increased frequency of intercourse; and increased libido. Despite multiple problems with Prentif caps, 67.4% of the cap recipients were still using their caps after one year. However, this was among a select group of highly motivated women of above-average intelligence. The causes of cap acceptability problems are discussed along with probable future improvements in cap design that may solve them.

The Prentif contraceptive cervical cap: a contemporary study of its clinical safety and effectiveness.

Because they seemed to be an overlooked, underutilized, and underdeveloped means of contraception, cervical caps were offered to patients in a private gynecological practice and the first 413 acceptors were sent a detailed questionnaire about their experiences. The 371 who responded provided generous amounts of information helpful in assessing not only cap safety and effectiveness, which are dealt with herein, but also in assessing acceptability which is dealt with in the companion article that follows. With regard to safety considerations, "cervical erosion" was not found to contraindicate cap use and no other significant safety hazards were encountered, although two concerns were suggested for further evaluation. The failure rate was 8.4 per 100 women per year by the life table method. Of 25 failures, 11 were labeled method failures and 14 were labeled human failures by the respondents themselves. The role of cap dislodgement as a cause of method failures is analyzed. It is concluded that caps are as safe and effective as diaphragms and that for many women they are the most suitable form of contraception available. It is reasonable to expect that they will soon be able to be approved for general use.

PIP: Cervical caps were offered to patients in a private gynecological practice in Massachusetts, and the first 413 acceptors were mailed a questionnaire asking about their experiences. The caps had been fitted between December 1977-September 1979. The only cap used in this study was the Prentif Cavity-Rim Cervical Cap. Delfen Cream was selected for the cap acceptors. 6 guidelines for satisfactory cap fitting are presented along with methods for training patients in the use of the cap. 371 acceptors returned their questionnaires; 8 had never used their caps after they left the office. 363 were included in the study, but all respondents did not answer all questions. With regard to safety considerations, "cervical erosion" was not found to contraindicate cap use. There were no other significant safety hazards. 4 of 253 respondents reported abnormal Pap tests since beginning cap use, but 3 of these women had had abnormal Pap tests shortly before they received their caps. No case of cervical cancer was found in any of the respondents. 12 of 255 respondents reported injuries to the cervix and vagina; 4 gave explanations that were clearly unrelated to cap use. 19% of 249 respondents reported that their menstrual periods had changed significantly since using the cap. The use of cervical caps had little, if any, "net" effect on the frequency of urinary tract infections. There were 25 pregnancies in 3243 months of exposure, yielding a Pearl Index of 9.25 pregnancies/l00 years of exposure. The failure rate was 8.4/100 women per year by the life table method. Of 25 pregnancies, 11 were labeled failures and 14 were labeled human failures by the respondents themselves. Dislodgement contributed importantly to the 11 method failures reported. In sum, the Prentif cap has been found to be as safe and effective as the diaphragm.

Changes in peripheral vascular and cardiac sympathetic activity before and after coronary artery bypass surgery: interrelationships with hemodynamic alterations.

The plasma catecholamine levels obtained simultaneously from radial artery (A), pulmonary artery (MV), brachial vein (PV), and coronary sinus (CS) were measured concurrent with hemodynamic determinations during coronary artery bypass graft (CABG) operations. Arterial catecholamine levels decreased after induction of anesthesia and increased after sternotomy; changes in veno-arterial norepinephrine (NE) differences ([PV-A]ne, [MV-A]ne, and [CS-A]ne) were of the same magnitude and direction, suggesting that NE release from various organs was of the same extent. After operation, arterial NE increased further, but the veno-arterial NE differences were in striking contrast; [PV-A]ne became markedly positive, whereas [CS-A]ne became markedly negative, indicating that NE release from extremity peripheral vasculature increased markedly while cardiac NE release decreased. These differential changes in regional sympathetic activity appear to be related to postoperative hypertension (HT) and low cardiac output (CO). There were close relationships of changes in [MV-A]ne to mean arterial pressure (r = 0.78, p less than 0.001) and systemic vascular resistance (r = 0.62, p less than 0.010, suggesting that the sympathetic nervous system plays an important role in CABG perioperative hemodynamic alterations.