Liposomes for Topical Use: A Physico-Chemical Comparison of Vesicles Prepared from Egg or Soy Lecithin

Developments in nanotechnology and in the formulation of liposomal systems provide the opportunity for cosmetic dermatology to design novel delivery systems. Determination of their physico-chemical parameters has importance when developing a nano-delivery system. The present study highlights some technological aspects/characteristics of liposomes formulated from egg or soy lecithins for topical use. Alterations in the pH, viscosity, surface tension, and microscopic/macroscopic appearance of these vesicular systems were investigated. The chemical composition of the two types of lecithin was checked by mass spectrometry. Caffeine, as a model molecule, was encapsulated into multilamellar vesicles prepared from the two types of lecithin: then zeta potential, membrane fluidity, and encapsulation efficiency were compared. According to our observations, samples prepared from the two lecithins altered the pH in opposite directions: egg lecithin increased it while soy lecithin decreased it with increased lipid concentration. Our EPR spectroscopic results showed that the binding of caffeine did not change the membrane fluidity in the temperature range of possible topical use (measured between 2 and 50 °C). Combining our results on encapsulation efficiency for caffeine (about 30% for both lecithins) with those on membrane fluidity data, we concluded that the interaction of caffeine with the liposomal membrane does not change the rotational motion of the lipid molecules close to the head group region. In conclusion, topical use of egg lecithin for liposomal formulations can be preferred if there are no differences in the physico-chemical properties due to the encapsulated drugs, because the physiological effects of egg lecithin vesicles on skin are significantly better than that of soy lecithin liposomes.     

Surgical recurrence in Crohn’s disease: a comparison between different types of bowel resections

Purpose

To compare recurrence frequency and location between different types of bowel resections in Crohn’s disease patients.

Methods

This was a retrospective study of consecutive patients undergoing bowel resection for Crohn’s disease between 2006 and 2016. Type of primary operation was recorded and grouped as ileocolic resection, small bowel resection, segmental colon resection with colocolic anastomosis or colorectal anastomosis, colectomy with ileorectal anastomosis, or end stoma operation. Binary logistic regression was used to compare surgical recurrence frequency between groups. We also investigated how Crohn’s disease location at reoperations was related to the primary bowel resection type.

Results

Altogether, 218 patients with a median follow-up of 4.7 years were included in our study. Reoperation was performed in 42 (19.3%) patients. The risk of reoperation using the ileocolic resection group as reference was the following: small bowel resection (odds ratio (OR) 2.95, 95% confidence interval (CI) 1.01–8.66; P?=?0.049), segmental colon resection with colocolic or colorectal anastomosis (OR 6.20, 95% CI 2.04–18.87; P?=?0.001), colectomy with ileorectal anastomosis (OR 26.57, 95% CI 2.59–273.01; P?=?0.006), and end stoma operation (OR 4.62, 95% CI 1.90–11.26; P?=?0.001). In case of surgical recurrence, the reoperation type and location correlated with the primary bowel resection type.

Conclusions

Reoperation frequency in Crohn’s disease is lower after ileocolic resection than after other types of bowel resections. Surgical recurrence in Crohn’s disease tends to maintain the disease location of the primary operation. One third of Crohn’s patients undergoing an end stoma operation will still need new bowel resections due to recurrence.

     

Impact of cardiac resynchronisation therapy on adaptation of circulatory and respiratory systems to exercise assessed by cardiopulmonary exercise test in patients with chronic heart failure

BACKGROUND: Cardiac resynchronisation therapy (CRT) has become a valuable therapeutic tool in patients with advanced chronic heart failure (CHF). The search for optimal methods for the assessment of CRT efficacy is still underway. AIM: To evaluate the impact of implantation of CRT devices in patients with CHF on adaptation of circulatory and respiratory systems to maximal exercise assessed by cardiopulmonary exercise tests (CPX) and 6-minute walking tests (6MWT). METHODS: We investigated 27 patients (22 males, 5 females, 61.2+/-9.1 years) with a CRT device implanted due to advanced CHF, which resulted from ischaemic or dilated cardiomyopathy. All patients before implantation underwent echocardiography, CPX with expired gas analysis and 6MWT. Investigations were repeated at 3-6 months after CRT implantation. In CPX we evaluated peak oxygen uptake (peak VO2), oxygen pulse, maximal minute ventilation-carbon dioxide production (VE/VCO2 (max)), and its slope (VE/VCO2 slope) and VE/VO2 slope, VO2 in anaerobic threshold (AT), and cardiac and respiratory reserve. In 6MWT we evaluated walking distance and heart rate and blood pressure response to exercise. RESULTS: We noted statistically higher mean peak VO2 after CRT implantation in the studied group: 11.34+/-3.38 vs. 14.56+/-3.99 ml/kg/min (p<0.0001) and 1.01 +/-0.44 vs. 1.4+/-0.55 l/min (p=0.003) and higher values of expired CO2: 1.00+/-0.43 vs. 1.43+/-0.67 l/min (p=0.004). The O2 pulse rose from 9.65+/-3.39 to 13.23+/-5.43 ml/beat (p=0.015). We also observed a significant reduction of VE/VCO2 slope from 42.34+/-13.35 before CRT to 34.77+/-6.04 after CRT (p=0.0196) and a significant decrease of VE/VO2 slope from 41.32 +/-15.46 to 34.01+/-6.27 (p=0.037). VE/VCO2 (max) fell from 58.02+/-15.86 to 50.1+/-13.14 (p=0.009). Patients estimated their dyspnoea on the Borg scale at peak exercise at 4.75+/-0.75 points before CRT and at 3.67+/-1.15 points (p=0.002) after CRT. Patients could walk a longer distance during 6MWT than before CRT (367+/-154.9 vs. 231.1+/-170.3 m, p<0.001). CONCLUSIONS: Cardiac resynchronisation therapy improves exercise tolerance measured by means of CPX and 6MWT, improves respiratory system efficiency and restores its adaptive mechanisms during exercise in patients with advanced CHF. Better exercise adaptation after CRT may be objectively measured with CPX parameters, and correlates with improvement of clinical symptoms. CPX seems to be a very helpful tool in assessing the results of CRT.     

Congenital CMV infection: prevalence in newborns and the impact on hearing deficit

Congenital cytomegalovirus (CMV) infection is asymptomatic in 90% of infected newborns but approximately 10-20% of these infants are at risk of developing sequelae later, mostly hearing deficit. The aims of the study were to investigate the prevalence of congenital CMV infection in a Swedish population of newborns and investigate the relative risk of hearing deficit in newborns with congenital CMV infection. The dried blood spot (DBS) samples of 6060 newborns in southern Stockholm during 12 months (October 2003-June 2004; August 2004-October 2004) were analysed for CMV DNA by TaqMan based real-time PCR. Hearing deficit was assessed by otoacoustic emission (OAE) within a newborn screening programme. 12 infants out of 6060 or 0.2% (95% CI 0.1-0.3%) had congenital CMV infection. One boy among the 12 infected infants had unilateral hearing loss, indicating that the risk of hearing loss is greatly increased (about 20 times) in CMV infected infants. No child developed ocular complications such as chorioretinopathy during 3 y of follow-up. Congenital CMV has an impact on child health but can easily be overlooked due to lack of signs in the neonatal period. Surveillance for congenital CMV is important in addition to programmes for prevention and treatment.     

Electrical remodeling in hearts from a calcium-dependent mouse model of hypertrophy and failure: complex nature of K+ current changes and action potential duration

OBJECTIVES: This study was designed to identify possible electrical remodeling (ER) in transgenic (Tg) mice with over-expressed L-type Ca(2+) channels. Transient outward K(+) current (I(to)) and action potential duration (APD) were studied in 2-, 4-, 8-, and 9- to 12-month-old mice to determine linkage to ventricular remodeling (VR), ER, and heart failure (HF). BACKGROUND: Prolongation of APD and reduction in current density of I(to) are thought to be hallmarks of VR and HF. Mechanisms are not understood. METHODS: Patch-clamp, perfused hearts, echocardiography, and Western blots were employed using 2-, 4-, 8-, and 9- to 12-month-old Tg mice. RESULTS: Transgenic mice developed slow VR statistically manifesting at four months and continuing through death at 12 to 14 months, despite a slight up-regulation of I(to). A slight decrease or no change in APD was observed up to eight months; however, at 9 to 12 months, a small increase in APD was detected. Early afterdepolarizations were observed after application of 4-aminopyridine in Tg mice. No change was detected in protein of Kv4.3 and Kv4.2 up to eight months. At 9 to 12 months, Tg mice showed a slight decrease (41.4 +/- 6.9%, p < 0.05) in Kv4.2, consistent with a decrease in I(to). Surprisingly, Kv1.4 (the "fetal" K(+)-channel form) was up-regulated, and restitution of I(to) was slowed. Echocardiography revealed cardiac enlargement with impaired chamber function in hearts that were taken from the older animals. CONCLUSIONS: Contrary to accepted dogma, APD and I(to) in a mouse model of hypertrophy and HF are not hallmarks of pathophysiology. We suggest that [Ca(2+)](i) (i.e., [Ca(2+)] concentration) is the primary factor in triggering cardiac enlargement and arrhythmogenesis.     

Pharmacological versus invasive treatment in patients with atrial fibrillation

Aim of this prospective study was to assess quality of life (QoL), left ventricular (LV) function and exercise performance in two groups of patients (pts) with atrial fibrillation (Af) treated with: radiofrequency catheter ablation (RFA) and antiarrhythmic drugs (AA). Between 1996 and 2000 - 74 patients, 28 women, with drug refractory Af were enrolled by clinical indications for two modes of therapy: RFA and AA. RFA group consisted of 38 pts, 63.7 +/- 11.5 years old: 28 pts with RF AV Node ablation and pacemaker implantation (PI) and 10 pts with AV Node modification or right atrial isthmus RF ablation due to Af conversion to atrial flutter (Aflu) during medical therapy. AA group consisted of 36 pts, aged 59.7 +/- 13.8 years. Patients from RFA group suffered significantly more serious diseases than pts from AA group. No significant (sign.) differences between two groups were found in age, gender, arrhythmia history and number of AA taken. Pts were analyzed before entry, after 3 and 12 months of follow-up (3 mo. FU, 12 mo. FU) with following indices: LV function (Echo: EF & FS), exercise performance (treadmill test), QoL questionnaires, number of hospital admissions connected to arrhythmia or procedures (RFA & PI), number of AA drugs taken in RFA group. RFA group: Two deaths occurred due to end stage respiratory insufficiency (COPD), one pt required reposition of pacemaker lead. AA group: 3 pts required RFA due to uncontrolled Af/Aflu (AV Node ablation with PI - 1 pt, right atrial isthmus ablation - 2 pts). Analysis of two patients groups: LV function: Sign. improvement (EF & FS) in both groups in 12 mo. FU; Exercise performance: no sign. changes in 3 and 12 mo. FU. QoL: Arrhythmia scale: 3 mo. FU sign. reduction in both groups; 12 mo. FU reduction in RFA group only; Anxiety scale: 3 and 12 mo. FU sign. reduction of anxiety level in RFA group; Exercise and activity scales: 3 and 12 mo. FU sign. improvement in RFA group. During 3 and 12 mo. FU sign. less pts from RFA group required hospital admission versus pts from AA group. Sign. reduction in AA was noted in RFA group. Patients with symptomatic Af treated with RFA benefit from this kind of therapy more than patients treated with AA. Quality of life improvement visible in short term observation in patients from RFA group is still present after one year observation. Improvement in LV function is observed after one year in both groups of pts with Af.     

Involvement of Oxygen-Derived Free Radicals in L-Arginine-Induced Acute Pancreatitis

This study was aimed at an assessment of the role of oxygen-derived free radicals in the pathogenesis of L-arginine (Arg)-induced acute pancreatitis in rat, by measuring the levels of malonyl dialdehyde (MDA), glutathione peroxidase (GPx), catalase, and superoxide dismutase (Mn- and Cu,Zn-SOD) in the pancreatic tissue, and evaluating the protective effect of the xanthine oxidase inhibitor allopurinol. Acute pancreatitis was induced in male Wistar rats by injecting 2 × 250 mg/100 g body weight of Arg intraperitoneally in a 1-hr interval, as a 20% solution in 0.15 M NaCl. Control rats received the same quantity of glycine. Allopurinol, 100 or 200 mg/kg, was administered subcutaneously 30 min before the first Arg injection. Rats were killed at 6, 12, 24, and 48 hr following Arg administration, and acute pancreatitis was confirmed by a serum amylase level elevation and typical inflammatory features observed microscopically. The serum level of amylase reached the peak level at 24 hr after the Arg injection (30,800 ± 3813 vs 6382 ± 184 units/liter in the control) and normalized at 48 hr. The tissue concentration of MDA was significantly elevated at 24 hr and reached the peak value at 48 hr (5.00 ± 1.75 vs 0.28 ± 0.05 nM/mg protein in the control). The catalase and Mn-SOD activities were significantly decreased throughout the study, while the GPx activity was significantly reduced at 6 and 12 hr, and the Cu,Zn-SOD activity was significantly lower at 12 hr after the Arg injection as compared with the controls. Allopurinol treatment markedly reduced the serum amylase elevation (12.631 ± 2.257 units/liter at 24 hr) and prevented the increase in tissue MDA concentration (0.55 ± 0.09 nM/mg protein at 48 hr). Both doses of allopurinol significantly ameliorated the pancreatic edema, necrosis, and inflammation at 48 hr after Arg administration. Oxygen-derived free radicals are generated at an early stage of Arg-induced acute pancreatitis. Prophylactic allopurinol treatment prevents the generation of reactive oxygen metabolites, reduces the serum amylase concentration, and exerts a beneficial effect on the development of histopathological changes.