Retinyl propionate and climbazole combination demonstrates clinical improvement to the appearance of hyperpigmentation and deep wrinkling with minimal irritation.

OBJECTIVE: To evaluate a combination of retinyl propionate and climbazole (RPC) compared to 0.1% retinol for its efficacy, tolerance and ageing appearance. METHOD: Forty-five healthy Caucasian females, ages 40-70, with moderately photodamaged facial skin, were recruited for a 16-week randomized, double-blind, IRB-approved facial study. The efficacy of RPC treatment was compared to 0.1% retinol, in the same product base formulation, with twice daily, split-face product application. Changes in overall photodamage, fine lines and wrinkles, pigmentation and irritation were visually evaluated and measured by instrumentation. Subjective appraisal of efficacy was self-assessed from images where subjects were blinded to treatment and time point. Irritancy potential was also evaluated in a 5-day randomized, double-blind, IRB-approved patch study. RESULTS: Treatment with RPC resulted in significant (P < 0.05) improvement in ageing attributes compared to 0.1% retinol treatment, with minimal irritation. More than 50% of subjects showed improvement to deep wrinkles in the crow's feet area after 5 weeks of product application, and continued improvement to deep wrinkles was observed throughout the course of the study. Similarly, improvement was observed for the appearance of lines and wrinkles in the nasolabial fold (NLF) and for mottled hyperpigmentation. The results from subjective self-assessment confirmed in vivo clinical assessments. In a separate patch study, significantly less irritation was observed with the RPC product as compared to the 0.1% retinol control product. CONCLUSION: RPC delivered significant skin anti-ageing benefits comparable or greater than 0.1% retinol, with minimal irritation.

Climbazole boosts activity of retinoids in skin.

OBJECTIVE: To explore whether climbazole enhances retinoid-associated biological activities in vitro and in vivo. METHODS: Primary human dermal fibroblasts (HDFs) were treated from six to 48 h with either retinoids (retinol, retinyl propionate, retinyl palmitate) alone or in combination with climbazole, and then assessed for cellular retinoic acid-binding protein 2 (CRABP2) mRNA expression by RT-qPCR. Next, skin equivalent (SE) cultures were topically treated with retinol or retinyl propionate, with or without climbazole, and then measured for biological changes in retinoid biomarkers. Lastly, an IRB-approved clinical study was conducted on the outer forearm of 16 subjects to ascertain the effects of low (0.02%) or high (0.1%) levels of retinol, retinyl propionate (0.5%), climbazole (0.5%) or a combination of retinol (0.02%)/climbazole (0.5%). Indicators of retinoid activities were measured after 3 weeks. RESULTS: Treatment of HDFs with retinol or retinyl propionate was unaffected by climbazole but alone, resulted in a significantly (P < 0.01) higher sustained CRABP2 mRNA expression than those treated with retinyl palmitate or vehicle control. In SEs, climbazole combined with either retinol or retinyl propionate boosted retinoid related activity greater than the retinoid only, reflected by a dose-response, downregulation of loricrin (LOR) and induction of keratin 4 (KRT4) proteins. In vivo, retinol (0.1%) and retinyl propionate (0.5%) significantly increased most evaluated biomarkers, as expected. Low-dose retinol or climbazole alone did not increase these biomarkers; however, in combination, significant (P < 0.05) increases in retinoid and ageing biomarkers were detected. CONCLUSION: Climbazole boosted retinoid activity both in the SE model, after a combined topic treatment with either retinol or retinyl propionate, and in vivo, in combination with a low level of retinol. Based upon the evidence presented here, we suggest that the topical skin application of climbazole in combination with retinoids could deliver skin ageing benefits more than a less robust retinoid alone.

The influence of endurance training intensity on dynamics of post-exertional heart rate recovery adaptation in patients with ischemic heart disease.

PURPOSE: The intensity of post-exertion heart rate recovery, evaluated in the first minute of the recovery period (HRR60), is considered to be a strong predictor of risk for cardiac death. Intensification of physical activity performed as part of cardiac rehabilitation (CR) increases the HRR60 value in ischemic heart disease (IHD) patients. In this context, the impact of endurance training intensity (ETI) on change in HRR60 intensity seems to be an interesting issue. MATERIAL/METHODS: The study group consisted of 251 patients who were subjected to a CR cycle. 45 patients of this group participated in CR twice. The control group consisted of 35 patients who were not subjected to any CR. ETI was estimated by the training work. In all patients an exertion test on a treadmill was performed twice within six months, analyzing the initial and final HRR60 value and ΔHRR60. RESULTS: After a six-month observation, there was a statistically significant increase in the HRR60 value (17.98±8.33/min vs. 22.72±7.72/min, p<0.01) in the test group, which was not observed in the control group. Mean ΔHRR60 value in the test group was statistically significantly greater than in the control group. In the subgroup subjected to the two CR cycles, only the first cycle led to a statistically significant increase in the mean HRR60 value. CONCLUSIONS: A six-month CR cycle significantly increased the HRR60 value, while cardiac training intensity did not affect the exertion-evoked change in its intensity. Continuation of the CR cycle beyond 6 months no longer significantly affected the change in the HRR60 value.

Dihalide and pseudohalide radical anions as oxidizing agents in nonaqueous solvents.

The dihalide and pseudohalide radical anions, strong one-electron oxidants, can be selectively generated in aqueous solutions by pulse radiolysis. Radiolysis of salts of the bulky 1-butyl-3-methylimidazolium cation with Cl(-), Br(-), SCN(-), and N(3)(-) anions allows efficient generation of the same species (Cl(2)(*-), Br(2)(*-), (SCN)(2)(*-), and N(6)(*-) radical anions) also in neat ionic liquids and in nonaqueous solvents with the addition of small amounts of the salt. The oxidative power of dichloride radical anion, lowered in the dichloromethane as compared to the aqueous solution, remains sufficient for oxidation of N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD, (2)k = (2.0 +/- 0.1) x 10(9) M(-1) s(-1)), phenothiazine (PZ, (2)k = (2.1 +/- 0.1) x 10(9) M(-1) s(-1)), 10-methylphenothiazine (MPZ, (2)k = (9.3 +/- 0.1) x 10(7) M(-1) s(-1)), and 3-methylindole (scatole, SCT, (2)k = (6.8 +/- 0.1) x 10(7) M(-1) s(-1)). It diminishes on going to Br(2)(*-) (reacts only with TMPD, (2)k = (5.4 +/- 0.3) x 10(8) M(-1) s(-1), and PZ, (2)k = (4.8 +/- 0.3) x 10(8) M(-1) s(-1)) while (SCN)(2)(*-) and N(6)(*-) radical anions oxidize only TMPD, (2)k = (5.1 +/- 0.5) x 10(8) M(-1) s(-1) and (2)k approximately 10(8) M(-1) s(-1), respectively.

1-Methylnicotinamide (MNA), a primary metabolite of nicotinamide, exerts anti-thrombotic activity mediated by a cyclooxygenase-2/prostacyclin pathway.

BACKGROUND AND PURPOSE: 1-methylnicotinamide (MNA) has been considered to be an inactive metabolite of nicotinamide. Here we assessed the anti-thrombotic activity of MNA in vivo. EXPERIMENTAL APPROACH: Antithrombotic action of MNA was studied in normotensive rats with extracorporeal thrombus formation (thrombolysis), in renovascular hypertensive rats with intraarterial thrombus formation (arterial thrombosis) and in a venous thrombosis model in rats (venous thrombosis). KEY RESULTS: MNA (3-100 mg kg(-1)) induced a dose-dependent and sustained thrombolytic response, associated with a rise in 6-keto-PGF(1alpha) in blood. Various compounds structurally related to MNA were either inactive or weaker thrombolytics. Rofecoxib (0.01-1 mg kg(-1)), dose-dependently inhibited the thrombolytic response of MNA, indomethacin (5 mg kg(-1)) abolished it, while L-NAME (5 mg kg(-1)) were without effect. MNA (3-30 mg kg(-1)) also reduced arterial thrombosis and this effect was abrogated by indomethacin (2.5 mg kg(-1)) as well as by rofecoxib (1 mg kg(-1)). MNA, however, did not affect venous thrombosis. In vitro MNA did not modify platelet aggregation nor induce vasodilation. CONCLUSIONS AND IMPLICATIONS: MNA displayed a profile of anti-thrombotic activity in vivo that surpasses that of closely related compounds. MNA inhibited platelet-dependent thrombosis by a mechanism involving cyclooxygenase-2 and prostacyclin. Our findings suggest that endogenous MNA, produced in the liver by nicotinamide N-methyltransferase, could be an endogenous activator of prostacyclin production and thus may regulate thrombotic as well as inflammatory processes in the cardiovascular system.

In search for new antipsoriatic agents: NAD topical composition.

The aim of the study was to examine the effectiveness of the oxidized form of nicotinamide adenine dinucleotide (NAD(+)), adenosine precursor, in 37 patients suffering from psoriasis. As NAD(+) is known to be relatively unstable, the second goal was to establish the proper conditions for the satisfactory stability of topical NAD(+) composition. In each patient, two matching plaques were selected for the study. Topical treatment with 1 or 0.3% NAD(+) in Vaseline ointment administered twice daily was compared with overnight therapy with 0.1% anthralin applied for 12 h and placebo. The enzymatic method was applied to determine the stability of NAD(+) in Vaseline ointment. After a 4-week application, the reduction in erythema, infiltration and desquamation caused by 1 or 0.3% topical NAD(+) composition was similar to the reduction caused by 0.1% anthralin. It was demonstrated that NAD(+) underwent a considerable decomposition at room temperature, while it was sufficiently stable at 5 degrees C; thus, for a longer use the agent should be stored at fridge temperature. NAD(+) therapy combines good efficacy, cosmetic acceptability and convenient twice-daily application.

Topical application of NADH for the treatment of rosacea and contact dermatitis.

Among many important physiological functions played by NADH (the reduced form of beta-nicotinamide adenine dinucleotide) its antioxidative properties are remarkable. Acting directly as an antioxidant, NADH can effectively protect the cell and its membrane from destruction by free radicals. NADH can be stabilized as a suspension in hydrophobic ointments prepared in a way that prevents contact with atmosphere containing oxygen and water. We present the first report of NADH as a treatment for some inflammatory dermatoses. It was found that topical application of 1% NADH diluted in Vaseline ointment can be very effective in the treatment of rosacea and contact dermatitis. Since no adverse effects were observed, therapy with NADH can be viewed as a potential alternative to other established treatments.

[Fibrinogen serum levels in patients with stable coronary artery disease and acute coronary syndrome]. / Stezenie fibrynogenu w surowicy chorych ze stabilna choroba wiencowa i ostrym zespolem wiencowym.

Increased plasma fibrinogen level is an important prognostic factor of recurrent unstable angina and myocardial infarction in patients with acute coronary syndrome (ACS). The aim of our study was to assess the plasma fibrinogen level at baseline condition in patients admitted to hospital due to coronary artery disease (CAD). Plasma fibrinogen was measured in 51 consecutive patients presenting with ACS within the last 24 hours and in 50 patients with angiographically proven CAD that was stable for the past 30 days. For statistical analysis Mann-Whitney U test, Student t-test, chi-square test and Pearson correlation was used, p < 0.05 being considered statistically significant. There was significant correlation between fibrinogen level and diagnosis of ACS or CAD (r = 0.29, p = 0.002). In our population plasma fibrinogen levels (g/L +/- SD) were significantly different in patients with ACS when compared to CAD subjects (3.87 +/- 1.2 vs. 3.26 +/- 0.65, p = 0.002). There was difference between ACS and CAD subjects in male:female ratio (40/11 vs. 47/4, p < 0.001) and age (63.4 +/- 10.1 vs. 58.4 +/- 10.0, p = 0.014). Our results confirm the role of fibrinogen in pathogenesis of CAD. In our opinion plasma fibrinogen level may be an important diagnostic tool in assessment of patients with chest pain.

The radical cation of syn-tricyclooctadiene and its rearrangement products

The syn dimer of cyclobutadiene (tricyclo[4.2.0.0(2.5)]octa-3,7-diene, TOD) is subjected to ionization under different conditions and the resulting species are probed by optical and ESR spectroscopy. By means of quantum chemical modelling of the potential energy surfaces and the optical spectra, it is possible to assign the different products that arise spontaneously after ionization or after subsequent warming or illumination of the samples. Based on these findings, we propose a mechanistic scheme which involves a partitioning of the incipient radical cation of TOD between two electronic states. These two states engage in (near) activation-less decay to the more stable valence isomers, cyclooctatetraene (COT*+) and a bis-cyclobutenylium radical cation BCB*+. The latter product undergoes further rearrangement, first to tetracyclo[4.2.0.0(2,4).0(3,5]oct-7-ene (TCO*+) and eventually to bicyclo[4.2.0]octa-2,4,7-triene (BOT*+) which can also be generated photochemically from BCB*+ or TCO*+. The surprising departure of syn-TOD*+ from the least-motion reaction path leading to BOT*+ can be traced to strong vibronic interactions (second-order Jahn-Teller effects) which prevail in both possible ground states of syn-TOD*+. Such effects seem to be more important in determining the intramolecular reactivity of radical cations than orbital or state symmetry rules.

Passive-fixation J-shaped versus straight leads in atrial position: comparison of efficacy and safety.

To compare the efficacy and safety of straight and J-shaped passive-fixation atrial leads we retrospectively analyzed the results of 100 consecutive implantations of atrial leads at one institution. There were seven cases of upgrades of VVIR to DDDR systems and in one case an active-fixation lead was chosen as a primary approach. These eight patients were excluded from the analysis. The final study group consisted of 92 cases (69 DDDR, 23 AAIR), 69 were J and 23 straight leads. The stimulation threshold, slew rate, impedance, P wave amplitude, and procedural time did not differ significantly between the two types of leads used. During the long-term follow-up of 6-53 months (30 +/- 11.9 months), replacements using active-fixation leads were required in two patients with straight leads and three patients with J leads (P = NS). In addition, one J lead showed signs of damage (impedance > 3,000 Ohm). Long-term follow-up values of the stimulation thresholds and P wave amplitudes did not differ between the groups (P = NS). Transesophageal echocardiography performed in 13 patients revealed a trend toward more distal placement of straight leads within the right atrial appendage. In conclusion, J-shaped leads do not seem to be superior to the straight leads for atrial implantations.

The terminal portion of the T wave: a new electrocardiographic marker of risk of ventricular arrhythmias.

Experimental studies have shown that transmural dispersion of repolarization (DoR), defined as the difference in action potential duration between mid-myocardial M-cells, epicardial, and endocardial cells is reflected in the duration of the terminal portion of the T wave (TpTe) on the surface ECG. Since DoR is an important factor associated with the propensity for reentrant arrhythmias, this study examined if TpTe may serve as a marker of risk of ventricular arrhythmias. Data from 18 patients with coronary artery disease and inducible sustained ventricular tachycardia (VT group) were compared with those of 16 survivors of myocardial infarction without inducible VT (control group). TpTe was automatically measured in each beat of 24-hour ECG recordings, and programmed ventricular stimulation was performed in the antiarrhythmic drug-free state. TpTe was expressed as the absolute interval in milliseconds, and relative to the duration of QTe (TpTe/QTe x 100%). TpTe duration was 74 +/- 14 ms in the VT group versus 63 +/- 16 ms in the control group (P < 0.004). The TpTe interval expressed as a percent of the QT interval was 21 +/- 4% in the VT group versus 17 +/- 3% in the control group (P = 0.02). In patients with coronary artery disease. TpTe was longer in patients with, versus without, inducible VT. The results of this study support the hypothesis that TpTe reflects transmural dispersion of repolarization.

[Permanent heart pacing in treatment of cardioinhibitory vasovagal syncope (case report)]. / Stala stymulacja serca w leczeniu postaci kardiodepresyjnej zespolu wazowagalnego (opis przypadku).

Vasovagal syncope is a complex syndrome in which specific methods of treatment rarely are related to clinical success. Since it turned out that some patients with neurocardiogenic syncope were resistant to offered pharmacotherapy, cardiac pacing has been used as the alternative way of long-term therapy. Successive studies, which have estimated clinical efficacy of permanent cardiac pacing, indicate that such method of treatment may reduce symptoms revealed by vasovagal reflex. Nevertheless the optimal pacing mode has not been established yet. It is known that single chamber VVI pacing is not a good and effective method whereas dual chamber DDI pacing with rate hysteresis seems to be very promising in treatment of people suffering from malignant cardioinhibitory vasovagal syncope. DDD pacing with rate drop response, search and scan functions recently has been available to these patients. The results of the North American Vasovagal Pacemaker Study, as well as some casuistic observations referring to patients with vasovagal syndrome, show very high clinical efficacy of dual chamber pacing with mentioned new functions. We present a case of patient with cardioinhibitory vasovagal syncope who was successfully treated by permanent DDD pacing with search and scan hysteresis.

Effects of amiodarone on the P-wave triggered signal-averaged electrocardiogram in patients with paroxysmal atrial fibrillation and coronary artery disease.

The effects of a 6-week treatment with amiodarone on the P-wave triggered signal-averaged electrocardiogram in patients with paroxysmal atrial fibrillation and coronary artery disease have been studied. Amiodarone favorably influences P-wave triggered signal-averaged electrocardiographic parameters, predominantly in patients in whom amiodarone is effective in preventing paroxysmal atrial fibrillation.

Perindopril for elderly people with chronic heart failure: the PEP-CHF study. The PEP investigators.

BACKGROUND: The prevalence of chronic heart failure (CHF) rises with increasing age, from < 1% in those below 65 years of age to > 5% in those over 65 years of age and is a major cause of morbidity and mortality in older people. Recent European guidelines point to a major deficiency in our knowledge of how to treat diastolic chronic heart failure, and a lack of information on treatment for heart failure in the elderly in general. AIMS: The aims of this trial are to assess the potential benefits of the ACE inhibitor perindopril to treat chronic heart failure in elderly people, in the absence of any major left ventricular systolic dysfunction. SUBJECTS: One thousand people over the age of 70 years will be recruited into this study. Evidence of chronic heart failure will be confirmed by clinical criteria and echocardiography. METHODS: Once a diagnosis of chronic heart failure has been confirmed, the patient will receive either perindopril or placebo in addition to their usual treatment. Death, and unplanned heart failure related hospitalisations, are the primary outcomes. Quality of life, as measured by the Guyatt questionnaire will be assessed at the beginning of the study and at 1 year. Sub-studies of this trial include a 6-min walking test and more detailed evaluation of ventricular function (as assessed by echocardiography). Both parameters will be measured at 8 weeks and 1 year, and analysed against baseline data. Cognitive function in this group of patients will also be evaluated at baseline and 1 year. This trial is due to report in the year 2001.

[The significance of scintigraphic, echocardiographic and electrocardiographic left atrial transesophageal pacing in diagnosis of ischemic heart disease]. / Znaczenie scyntygraficznego, echokardiograficznego i elektrokardiograficznego testu stymulacji przezprzelykowej lewego przedsionka w diagnostyce choroby niedokrwiennej serca.

UNLABELLED: The aim of the study was to compare the perfusion scintigraphy (using SPECT method with Tc-99-MIBI) during left atrial transoesophageal pacing test (LAPT) with pacing electrocardiography (ECG), echocardiography (ECHO) and electrocardiography exercise test (ExT) in ischaemic heart disease (IHD) diagnostics. The effect of LATP on heart haemodynamic parameters and the correlation between scintigraphic, echocardiographic and electrocardiographic parameters during LAPT test have been also assessed. Investigations were carried out in 55 subjects (Group I: 36 patients with effort angina pectoris; group II: controls: 19 clinically healthy subjects). Coronarography was performed in 24 patients 6 weeks before or after examinations. LATP test was analyzed with ECG, ECHO and SPECT. Echocardiography did not increase significantly the LATP test diagnostic value. Perfusion scintigraphy enhanced sensitivity and predictive excluding value LATP test. These values were 93.3% v 62.9% and 90% v 59.3% respectively. LATP test assessed with ECG, ECHO and perfusion scintigraphy expressed significantly higher sensitivity and predicting excluding value in comparison to ExT. LATP test analyzed in such way was characterized by 100% sensitivity and 100% predicting excluding value. CONCLUSION: Combination of LATP with electrocardiography, echocardiography and SPECT is a non-invasive high quality method for ischaemic heart disease diagnostics.

Three-dimensional echocardiographic evaluation of left ventricular volume: comparison of Doppler myocardial imaging and standard gray-scale imaging with cineventriculography--an in vitro and in vivo study.

BACKGROUND: Standard gray-scale imaging (GSI), three-dimensional (3D) echocardiography has been shown to be superior to two-dimensional echocardiography in measuring left ventricular volume. However, the often relatively poor quality of transthoracic gray-scale data can limit the potential application of this technique. Doppler myocardial imaging (DMI) is a new ultrasound technique that potentially offers higher-quality 3D images with a transthoracic approach than the 3D GSI technique. This study was designed to compare the accuracy of standard GSI and DMI 3D left ventricular volume measurements in vitro and in vivo. METHODS AND RESULTS: In vitro, the minimum and maximum volume of the contracting single-chamber, tissue-mimicking phantom was calculated by using both techniques. In vivo, GSI and DMI 3D left ventricular volume measurements were performed in 16 patients. End-diastolic and end-systolic left ventricular volumes were computed for both techniques and compared with those calculated by cineventriculography. In vitro, both methods tended to underestimate the true phantom volume, but the systematic error was smaller for DMI than for GSI (-1.2% +/- 1.5% vs. -4.3% +/- 3%; p < 0.01) and was more constant in the case of DMI over the range of different sizes of true volume. In vivo, for GSI the end-diastolic volume mean difference was -12.6 ml and the limits of agreement were +/-18 ml, and for DMI the corresponding values were -4.2 and +/- 10.6 ml, respectively. The difference for end-systole was -6.5 +/- 10.6 ml and -1.5 +/- 10 ml for GSI and DMI, respectively. The magnitude of the difference in volume measurement between 3D echocardiography and cineventriculography was significantly smaller when using the Doppler technique. CONCLUSIONS: The results of this in vitro and in vivo study indicate that DMI is superior to GSI as a transthoracic acquisition technique for 3 D volume computation.

Antiviral activity of 1,7-disulphoanthraquinone.

The antiviral activity of 1,7-disulphoanthraquinone (DSA) against hepatitis B viruses was investigated by measuring the titer of HBV surface antigen in the treated serum obtained from the blood of patients with acute infection. The presence of HBsAg was tested by the Vitek Immuno Diagnostic Assay System (VIDAS). The concentration of DSA in the samples was equal to 0.01, 0.1 and 1%, respectively. The results presented clearly showed an extensive disintegration of the virus envelope at elevated temperatures, which resulted in a substantial decrease in the concentration of HBsAg in the serum containing DSA. The concentration of HBsAg decreased also upon UV irradiation of the serum containing DSA in a photochemical reactor for 5 to 15 min, but the effect of degradation was not complete.

[The improvement of echocardiographic assessment of the left ventricle by the use of perflenapent and harmonic imaging]. / Poprawa echokardiograficznej oceny lewej komory przy zastosowaniu perflenapentu i obrazowania harmonicznego.

Contrast echocardiography and harmonic imaging (HI) are promising new modalities applied in order to obtain improved visualisation of the left ventricle. Perflenapent (EchoGen, Abbott) is a new generation echocardiographic contrast agent that crosses the pulmonary capillary bed and produces long-term ventricle opacification. Our aim was to assess the left ventricle endocardial visualisation after perflenapent infusion and HI technique. We studied a pilot group of 10 patients (mean age 52.5 +/- 7.6, mean weight 76.9 +/- 10.1 kg, one female) with previously obtained sub-optimal non-contrast echocardiograms. Perflenapent was injected intravenously at dosis 0.05 ml/kg. Echocardiography was performed before perflenapent injection and during the time between injection and LV image disappearance. Images were assessed using four-point scale, 0 standing for the poorest and 3 for excellent visualisation. Perflenapent produced full chamber opacification in all pts. Contrast effect was observed for 550-15824 sec and myocardial enhancement was seen for 176-2116 sec after i.v. administration. After perflenapent administration, endocardial border was significantly better visible than before (1.9 +/- 0.57 vs. 2.9 +/- 0.31, p < 0.001). No hemodynamic effects were noted, as assessed by oxygen saturation, blood pleasure and heart rate. A mild, transient somnolence was seen in one pt. Perflenapent improved left ventricular function diagnostic capabilities, and provided enhanced visualisation of the myocardium.

QT dispersion magnitude is related to the respiratory phase in healthy subjects.

Twelve-lead electrocardiograms in 20 healthy volunteers during quiet respiration, maximum inspiration, and maximum expiration were recorded. QT dispersion was statistically significantly shorter both at maximum inspiration and maximum expiration than during quiet breathing.