Iron supplementation reduces the erosive potential of a cola drink on enamel and dentin in situ

Iron has been suggested to reduce the erosive potential of cola drinks in vitro. Objective: The aim of this study was to evaluate in situ the effect of ferrous sulfate supplementation on the inhibition of the erosion caused by a cola drink. Material and Methods: Ten adult volunteers participated in a crossover protocol conducted in two phases of 5 days, separated by a washout period of 7 days. In each phase, they wore palatal devices containing two human enamel and two human dentin blocks. The volunteers immersed the devices for 5 min in 150 mL of cola drink (Coca-Cola (TM), pH 2.6), containing ferrous sulfate (10 mmol/L) or not (control), 4 times per day. The effect of ferrous sulfate on the inhibition of erosion was evaluated by profilometry (wear). Data were analyzed by paired t tests (p<0.05). Results: The mean wear (+/- se) was significantly reduced in the presence of ferrous sulfate, both for enamel (control: 5.8 +/- 1.0 mu m; ferrous sulfate: 2.8 +/- 0.6 mu m) and dentin (control: 4.8 +/- 0.8 mu m; ferrous sulfate: 1.7 +/- 0.7 mu m). Conclusions: The supplementation of cola drinks with ferrous sulfate can be a good alternative for the reduction of their erosive potential. Additional studies should be done to test if lower ferrous sulfate concentrations can also have a protective effect as well as the combination of ferrous sulfate with other ions.

Application of H-infinity Theory to a 6 DOF Flight Simulator Motion Base

The purpose of this study is to apply inverse dynamics control for a six degree of freedom flight simulator motion system. Imperfect compensation of the inverse dynamic control is intentionally introduced in order to simplify the implementation of this approach. The control strategy is applied in the outer loop of the inverse dynamic control to counteract the effects of imperfect compensation. The control strategy is designed using H-infinity theory. Forward and inverse kinematics and full dynamic model of a six degrees of freedom motion base driven by electromechanical actuators are briefly presented. Describing function, acceleration step response and some maneuvers computed from the washout filter were used to evaluate the performance of the controllers.

Chronic Conventional resistance exercise reduces blood pressure in stage 1 Hypertensive men

Moraes, MR, Bacurau, RFP, Casarini, DE, Jara, ZP, Ronchi, FA, Almeida, SS, Higa, EMS, Pudo, MA, Rosa, TS, Haro, AS, Barros, CC, Pesquero, JB, Wurtele, M, and Araujo, RC. Chronic conventional resistance exercise reduces blood pressure in stage 1 hypertensive men. J Strength Cond Res 26(4): 1122-1129, 2012-To investigate the antihypertensive effects of conventional resistance exercise (RE) on the blood pressure (BP) of hypertensive subjects, 15 middle-aged (46 +/- 3 years) hypertensive volunteers, deprived of antihypertensive medication (reaching 153 +/- 6/93 +/- 2 mmHg systolic/diastolic BP after a 6-week medication washout period) were submitted to a 12-week conventional RE training program (3 sets of 12 repetitions at 60% 1 repetition maximum, 3 times a week on nonconsecutive days). Blood pressure was measured in all phases of the study (washout, training, detraining). Additionally, the plasma levels of several vasodilators or vasoconstrictors that potentially could be involved with the effects of RE on BP were evaluated pre- and posttraining. Conventional RE significantly reduced systolic, diastolic, and mean BP, respectively, by an average of 16 (p < 0.001), 12 (p < 0.01), and 13 mm Hg (p < 0.01) to prehypertensive values. There were no significant changes of vasoactive factors from the kallikrein-kinin or renin-angiotensin systems. After the RE training program, the BP values remained stable during a 4-week detraining period. Taken together, this study shows for the first time that conventional moderate-intensity RE alone is able to reduce the BP of stage 1 hypertensive subjects free of antihypertensive medication. Moreover, the benefits of BP reduction achieved with RE training remained unchanged for up to 4 weeks without exercise.

A Randomized Trial of Noninvasive Positive End Expiratory Pressure in Patients With Acquired Immune Deficiency Syndrome and Hypoxemic Respiratory Failure

BACKGROUND: Acquired immunodeficiency syndrome (AIDS) is a pandemic disease commonly associated with respiratory infections, hypoxemia, and death. Noninvasive PEEP has been shown to improve hypoxemia. In this study, we evaluated the physiologic effects of different levels of noninvasive PEEP in hypoxemic AIDS patients. METHODS: Thirty AIDS patients with acute hypoxemic respiratory failure received a randomized sequence of noninvasive PEEP (5, 10, or 15 cm H2O) for 20 min. PEEP was provided through a facial mask with pressure-support ventilation (PSV) of 5 cm H2O and an F-IO2, of 1. Patients were allowed to breathe spontaneously for a 20-min washout period in between each PEEP trial. Arterial blood gases and clinical variables were recorded after each PEEP treatment. RESULTS: The results indicate that oxygenation improves linearly with increasing levels of PEEP. However, oxygenation levels were similar regardless of the first PEEP level administered (5, 10, or 15 cm H2O), and only the subgroup that received an initial treatment of the lowest level of PEEP (ie, 5 cm H2O) showed further improvements in oxygenation when higher PEEP levels were subsequently applied. The P-aCO2, also increased in response to PEEP elevation, especially with the highest level of PEEP (ie, 15 cm H2O). PSV of 5 cm H2O use was associated with significant and consistent improvements in the subjective sensations of dyspnea and respiratory rate reported by patients treated with any level of PEEP (from 0 to 15 cm H2O). CONCLUSIONS: AIDS patients with hypoxemic respiratory failure improve oxygenation in response to a progressive sequential elevation of PEEP (up to 15 cm H2O). However, corresponding elevations in P-aCO2, limit the recommended level of PEEP to 10 cm H2O. At a level of 5 cm H2O, PSV promotes an improvement in the subjective sensation of dyspnea regardless of the PEEP level employed.

In Situ Effect of Dentifrices Associated to CO2 Laser in the Permeability of Eroded Root Dentin

Objective: The aim of this study was to evaluate, through a crossover 2 x 2 in situ trial, the effect of a desensitizing dentifrice associated with CO2 laser irradiation to control the permeability of eroded root dentin. Background data: Facing the increased prevalence of erosive lesion and the need for preventive means to control painful symptoms related to them. Methods: Eighty slabs of bovine root dentin were subjected to initial erosive challenge (citric acid 0.3%, 2 h), followed by a remineralizing period in artificial saliva (24 h). Specimens were then divided according to dentin treatment: desensitizing dentifrice, desensitizing dentifrice + CO2 laser, fluoride anticavity dentifrice. and fluoride anticavity dentifrice + CO2 laser. After a 2-day lead-in period, 10 volunteers wore an intraoral palatal appliance containing four root dentin slabs, in two phases of 5 days each. During the intraoral phase, one side of the appliance was immersed in 0.3% citric acid, and the opposite side was immersed in deionized water, four times a day. One hour after the immersions, all specimens were brushed with dentifrice slurry provided by the researcher. After a 7-day washout period, volunteers were crossed over on the different dentifrice group. Each phase having been completed, the specimens were evaluated for permeability through an optical microscope. Results: Data were analyzed using ANOVA and no significant difference (p = 0.272) was found between the surface treatments performed on bovine root dentin. Conclusions: It can be concluded that fluoride anticavity or desensitizing dentifrice, regardless of the association with the CO2 laser irradiation, was able to control the permeability of eroded root dentin.

Metronidazole Immediate Release Formulations: A Fasting Randomized Open-Label Crossover Bioequivalence Study in Healthy Volunteers

Metronidazole is a BCS (Biopharmaceutics Classification System) class 1 drug, traditionally considered the choice drug in the infections treatment caused by protozoa and anaerobic microorganisms. This study aimed to evaluate bioequivalence between 2 different marketed 250 mg metronidazole immediate release tablets. A randomized, open-label, 2 x 2 crossover study was performed in healthy Brazilian volunteers under fasting conditions with a 7-day washout period. The formulations were administered as single oral dose and blood was sampled over 48 h. Metronidazole plasma concentrations were determined by a liquid chromatography mass spectrometry (LC-MS/MS) method. The plasma concentration vs. time profile was generated for each volunteer and the pharmacokinetic parameters C-max, T-max, AUC(0-t), AUC(0-infinity), k(e), and t(1/2) were calculated using a noncompartmental model. Bioequivalence between pharmaceutical formulations was determined by calculating 90% CIs (Confidence Intervall) for the ratios of C-max, AUC(0-t), and AUC(0-infinity) values for test and reference using log-transformed data. 22 healthy volunteers (11 men, 11 women; mean (SD) age, 28 (6.5) years [range, 21-45 years]; mean (SD) weight, 66 (9.3) kg [range, 51-81 kg]; mean (SD) height, 169 (6.5) cm [range, 156-186 cm]) were enrolled in and completed the study. The 90% CIs for C-max (0.92-1.06), AUC(0-t) (0.97-1.02), and AUC(0-infinity) (0.97-1.03) values for the test and reference products fitted in the interval of 0.80-1.25 proposed by most regulatory agencies, including the Brazilian agency ANVISA. No clinically significant adverse effects were reported. After pharmacokinetics analysis, it concluded that test 250 mg metronidazole formulation is bioequivalent to the reference product according to the Brazilian agency requirements.

A Phase I clinical trial of lodenafil carbonate, a new phosphodiesterase Type 5 (PDE5) inhibitor, in healthy male volunteers

Lodenafil carbonate is a new phosphodiesterase Type 5 (PDE5) inhibitor used in treatment of erectile dysfunction. Objective: The present study was conducted to evaluate the safety, tolerability, and pharmacokinetics of lodenafil carbonate after administering ascending (1 - 100 mg) single oral doses to healthy male volunteers (n = 33). Methods: The study was an open-label, dose-escalation, Phase I clinical trial involving the administration of single oral doses of lodenafil carbonate. Lodenafil carbonate was administered sequentially, escalating in single doses of 1 mg - 100 mg with a washout period of at least 1 week between each dose. The progression to the next dose was allowed after clinical and laboratory exams, Ambulatory Monitoring of Arterial Pressure (AMAP) without relevant clinical modifications and adverse events without clinical relevancy. Blood samples were collected at pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 14, 16, 20 and 24 h post-dosing. Plasma samples for measurement of lodenafil carbonate and lodenafil were analyzed by liquid chromatography coupled to tandem mass spectrometry. Results: No serious adverse events were observed, and none of the subjects discontinued the study due to intolerance. The AMAP measurements, clinical and laboratory exams and ECG revealed no significant changes even at higher doses. Lodenafil carbonate was not detected in any samples, indicating that it acts as a prodrug. The mean lodenafil pharmacokinetic parameters for t(max) and t(1/2) were 1.6 (+/- 0.4) h and 3.3 (+/- 1.1) h, respectively. This study demonstrated that lodenafil carbonate was well tolerated and showed a good safety profile in healthy male volunteers.

Metformin, but not glimepiride, improves carotid artery diameter and blood flow in patients with type 2 diabetes mellitus

OBJECTIVE: To compare the effects of glimepiride and metformin on vascular reactivity, hemostatic factors and glucose and lipid profiles in patients with type 2 diabetes. METHODS: A prospective study was performed in 16 uncontrolled patients with diabetes previously treated with dietary intervention. The participants were randomized into metformin or glimepiride therapy groups. After four months, the patients were crossed over with no washout period to the alternative treatment for an additional four-month period on similar dosage schedules. The following variables were assessed before and after four months of each treatment: 1) fasting glycemia, insulin, catecholamines, lipid profiles and HbA(1) levels; 2) t-PA and PAI-1 (antigen and activity), platelet aggregation and fibrinogen and plasminogen levels; and 3) the flow indices of the carotid and brachial arteries. In addition, at the end of each period, a 12-hour metabolic profile was obtained after fasting and every 2 hours thereafter. RESULTS: Both therapies resulted in similar decreases in fasting glucose, triglyceride and norepinephrine levels, and they increased the fibrinolytic factor plasminogen but decreased t-PA activity. Metformin caused lower insulin and pro-insulin levels and higher glucagon levels and increased systolic carotid diameter and blood flow. Neither metformin nor glimepiride affected endothelial-dependent or endothelial-independent vasodilation of the brachial artery. CONCLUSIONS: Glimepiride and metformin were effective in improving glucose and lipid profiles and norepinephrine levels. Metformin afforded more protection against macrovascular diabetes complications, increased systolic carotid artery diameter and total and systolic blood flow, and decreased insulin levels. As both therapies increased plasminogen levels but reduced t-PA activity, a coagulation process was likely still ongoing.

Brazilian blood donation eligibility criteria for dermatologic patients

A focused and commented review on the impact of dermatologic diseases and interventions in the solidary act of donating blood is presented to dermatologists to better advise their patients. This is a review of current Brazilian technical regulations on hemotherapeutic procedures as determined by Ministerial Directive #1353/2011 by the Ministry of Health and current internal regulations of the Hemotherapy Center of Ribeirão Preto, a regional reference center in hemotherapeutic procedures. Criteria for permanent inaptitude: autoimmune diseases (>1 organ involved), personal history of cancer other than basal cell carcinoma, severe atopic dermatitis or psoriasis, pemphigus foliaceus, porphyrias, filariasis, leprosy, extra pulmonary tuberculosis or paracoccidioidomycosis, and previous use of etretinate. Drugs that impose temporary ineligibility: other systemic retinoids, systemic corticosteroids, 5-alpha-reductase inhibitors, vaccines, methotrexate, beta-blockers, minoxidil, anti-epileptic, and anti-psychotic drugs. Other conditions that impose temporary ineligibility: occupational accident with biologic material, piercing, tattoo, sexually transmitted diseases, herpes, and bacterial infections, among others. Discussion: Thalidomide is currently missing in the teratogenic drugs list. Although finasteride was previously considered a drug that imposed permanent inaptitude, according to its short halflife current restriction of 1 month is still too long. Dermatologists should be able to advise their patients about proper timing to donate blood, and discuss the impact of drug withdrawal on treatment outcomes and to respect the designated washout periods.

Application of H∞ theory to a 6 DOF flight simulator motion base

The purpose of this study is to apply inverse dynamics control for a six degree of freedom flight simulator motion system. Imperfect compensation of the inverse dynamic control is intentionally introduced in order to simplify the implementation of this approach. The control strategy is applied in the outer loop of the inverse dynamic control to counteract the effects of imperfect compensation. The control strategy is designed using H∞ theory. Forward and inverse kinematics and full dynamic model of a six degrees of freedom motion base driven by electromechanical actuators are briefly presented. Describing function, acceleration step response and some maneuvers computed from the washout filter were used to evaluate the performance of the controllers.

Motivation and frustration in cardiology trial participation: the patient perspective

OBJECTIVE: The participation of humans in clinical cardiology trials remains essential, but little is known regarding participant perceptions of such studies. We examined the factors that motivated participation in such studies, as well as those that led to participant frustration. METHODS: Patients who had participated in hypertension and coronary arterial disease (phases II, III, and IV) clinical trials were invited to answer a questionnaire. They were divided into two groups: Group I, which included participants in placebo-controlled clinical trials after randomization, and Group II, which included participants in clinical trials in which the tested treatment was compared to another drug after randomization and in which a placebo was used in the washout period. RESULTS: Eighty patients (47 patients in Group I and 33 patients in Group II) with different socio-demographic characteristics were interviewed. Approximately 60% of the patients were motivated to participate in the trial with the expectation of personal benefit. Nine participants (11.2%) expressed the desire to withdraw, which was due to their perception of risk during the testing in the clinical trial (Group I) and to the necessity of repeated returns to the institution (Group II). However, the patients did not withdraw due to fear of termination of hospital treatment. CONCLUSIONS: Although this study had a small patient sample, the possibility of receiving a benefit from the new tested treatment was consistently reported as a motivation to participate in the trials.

A clinical comparison between DisCoVisc and 2% hydroxypropylmethylcellulose in phacoemulsification: a fellow eye study

OBJECTIVE: This study sought to compare the effects and outcomes of two ophthalmic viscosurgical devices, 1.6% hyaluronic acid/4.0% chondroitin sulfate and 2.0% hydroxypropylmethylcellulose, during phacoemulsification. METHODS: This prospective, randomized clinical trial comprised 78 eyes (39 patients) that received phacoemulsification performed by the same surgeon using a standardized technique. Patients were randomly assigned to receive either 1.6% hyaluronic acid/4.0% chondroitin sulfate or 2.0% hydroxypropylmethylcellulose on the first eye. The other eye was treated later and received the other viscoelastic agent. Preoperative and postoperative examinations (5, 24 and 48 hours; 7 and 14 days; 3 and 6 months) included measurements of the total volume of the ophthalmic viscosurgical device, ultrasound and washout times to completely remove the ophthalmic viscosurgical device, intraocular pressure, central corneal thickness and best-corrected visual acuity. The corneal endothelial cell count was measured at baseline and at six months postoperatively. ClinicalTrials.gov: NCT01387620. RESULTS: There were no statistically significant differences between groups in terms of cataract density or ultrasound time. However, it took longer to remove 2.0% hydroxypropylmethylcellulose than 1.6% hyaluronic acid/ 4.0% chondroitin sulfate, and the amount of viscoelastic material used was greater in the 2.0% hydroxypropylmethylcellulose group. In addition, the best-corrected visual acuity was significantly better in the hyaluronic acid/ chondroitin sulfate group, but this preferable outcome was only observed at 24 hours after the operation. There were no statistically significant differences between the two ophthalmic viscosurgical devices regarding the central corneal thickness or intraocular pressure measurements at any point in time. The corneal endothelial cell count was significantly higher in the hyaluronic acid/chondroitin sulfate group. CONCLUSION: The ophthalmic viscosurgical device consisting of 1.6% hyaluronic acid/4.0% chondroitin sulfate was more efficient during phacoemulsification and was easier to remove after IOL implantation than 2.0% hydroxypropylmethylcellulose. In addition, the corneal endothelial cell count was significantly higher following the use of hyaluronic acid/chondroitin sulfate than with hydroxypropylmethylcellulose, which promoted an improved level of corneal endothelium protection.

Synthese und radioaktive Markierung potentieller PET- bzw. SPECT-Liganden zur Quantifizierung und Visualisierung der pankreatischen beta-Zell-Masse

Abstract Due to the ongoing efforts in transplanting b-cell mass there is also a great medical interest in specific b-cell imaging agents to quantify the acceptance of transplanted islets in humans in vivo. Additionally, in the context of type 1 diabetes mellitus the chronic and progressive loss of b-cells caused by autoimmune destruction has led to concerted efforts to prevent further loss of b-cells by autoantigen-specific immunotherapy of pre-diabetic patients. nateglinide and glibenclamide are SUR1 ligands used to stimulate insulin secretion in type 2 diabetic patients. They bind to a class of molecules known as the ATP-sensitive potassium channels, located on the insulin producing b-cells of the islets of Langerhans and are therefore excellent candidates as b-cell specific tracers. To obtain a precursor for a direct labelling of nateglinide with [18F]fluoride, the aromatic system of the phenylalanine structure element was derivatised to obtain a phenolic OH-group in 4-position which is capable of further derivatisation. The formed phenylether N-(trans-4-isopropylcyclohexanecarbonyl)-O-(2-hydroxyethyl)-D-tyrosin benzylester was tried to be tosylated according to several literature procedures but none of them was applicable. The catalytic influence of ytterbium(III)triflate in the reaction of toluenesulfonic acid anhydride and the alcohol was investigated. It was found that Yb(III) facilitates the tosylation of the alcohol under non-basic conditions and was extended to the tosylation of a great variety of different alcohols to prove its applicability in general. The radioactive labelling of N-(trans-4-isopropyl-cyclohexanecarbonyl)-O-(2-[18F]fluoroethyl)-D-tyrosine with [18F]F-/ Kryptofix® 222/ K2CO3-system was achieved in radiochemical yields (RCY) of 10 % after deprotection with Pd/ C and H2. In addition to the direct labelling approach, a labelling procedure applying 2[18F]fluoroethyltosylate and N-(trans-4-isopropyl-cyclohexanecarbonyl)-D-tyrosin was performed in 40 % RCY. Unfortunately the determination of the KD value of N-(trans-4-isopropylcyclohexanecarbonyl)-O-(2-fluoroethyl)-D-tyrosine revealed a significant decrease in affinity compared to original nateglinide. The in vivo evaluation of some 18F-labelled glibenclamide derivatives in humans and animals revealed that longer measuring times are warranted because a high liver uptake spoiles the data acquisition and the activity washout proceeds very slowly. Therefore glibenclamide was labelled with a radioisotope with a longer half life such as 99mTc (t1/2 = 6 h) to lengthen the possible time frame for image acquisition. The synthesis of a 99mTc labelled hydrophilic glibenclamide derivative was performed. It is hoped that gliben-clamide is internalised into the b-cell and there binds to the 95 % of intracellular SUR-1 receptors with eventual metablolisation and thus trapping in the cell. The KD-value of the corresponding Re-compound was determined to be 0.5 nM and the insulin secretion properties were similar to those of original glibenclamide. The labelling precursor N-{4-[N,N-bis-(carboxy-methyl)-aminoethyl)-5-chlorobenzene-carboxamido]-ethyl}-benzene-sulfonyl-N'-cyclohexyl urea tris sodium salt was reacted with [99mTc(I)(OH2)3(CO)3] Cl to yield the final N-{4-[99mTc(I)-tricarbonyl-N,N-bis-(carboxymethyl)-aminoethyl)-5-chloro-benzene-carboxamidoethyl]-benzene-sulfonyl}-N'-cyclo-hexyl-urea sodium salt in 70% RCY.

Normative data for lung function and exhaled nitric oxide in unsedated healthy infants

Despite association with lung growth and long-term respiratory morbidity, there is a lack of normative lung function data for unsedated infants conforming to latest European Respiratory Society/American Thoracic Society standards. Lung function was measured using an ultrasonic flow meter in 342 unsedated, healthy, term-born infants at a mean ± sd age of 5.1 ± 0.8 weeks during natural sleep according to the latest standards. Tidal breathing flow-volume loops (TBFVL) and exhaled nitric oxide (eNO) measurements were obtained from 100 regular breaths. We aimed for three acceptable measurements for multiple-breath washout and 5-10 acceptable interruption resistance (R(int)) measurements. Acceptable measurements were obtained in ≤ 285 infants with high variability. Mean values were 7.48 mL·kg⁻¹ (95% limits of agreement 4.95-10.0 mL·kg⁻¹) for tidal volume, 14.3 ppb (2.6-26.1 ppb) for eNO, 23.9 mL·kg⁻¹ (16.0-31.8 mL·kg⁻¹) for functional residual capacity, 6.75 (5.63-7.87) for lung clearance index and 3.78 kPa·s·L⁻¹ (1.14-6.42 kPa·s·L⁻¹) for R(int). In males, TBFVL outcomes were associated with anthropometric parameters and in females, with maternal smoking during pregnancy, maternal asthma and Caesarean section. This large normative data set in unsedated infants offers reference values for future research and particularly for studies where sedation may put infants at risk. Furthermore, it highlights the impact of maternal and environmental risk factors on neonatal lung function.

Optimizing human in vivo dosing and delivery of β-alanine supplements for muscle carnosine synthesis

Interest into the effects of carnosine on cellular metabolism is rapidly expanding. The first study to demonstrate in humans that chronic β-alanine (BA) supplementation (~3-6 g BA/day for ~4 weeks) can result in significantly augmented muscle carnosine concentrations (>50%) was only recently published. BA supplementation is potentially poised for application beyond the niche exercise and performance-enhancement field and into other more clinical populations. When examining all BA supplementation studies that directly measure muscle carnosine (n=8), there is a significant linear correlation between total grams of BA consumed (of daily intake ranges of 1.6-6.4 g BA/day) versus both the relative and absolute increases in muscle carnosine. Supporting this, a recent dose-response study demonstrated a large linear dependency (R2=0.921) based on the total grams of BA consumed over 8 weeks. The pre-supplementation baseline carnosine or individual subjects' body weight (from 65 to 90 kg) does not appear to impact on subsequent carnosine synthesis from BA consumption. Once muscle carnosine is augmented, the washout is very slow (~2%/week). Recently, a slow-release BA tablet supplement has been developed showing a smaller peak plasma BA concentration and delayed time to peak, with no difference in the area under the curve compared to pure BA in solution. Further, this slow-release profile resulted in a reduced urinary BA loss and improved retention, while at the same time, eliciting minimal paraesthesia symptoms. However, our complete understanding of optimizing in vivo delivery and dosing of BA is still in its infancy. Thus, this review will clarify our current knowledge of BA supplementation to augment muscle carnosine as well as highlight future research questions on the regulatory points of control for muscle carnosine synthesis.