The effect of chamomile extract obtained in supercritical carbon dioxide conditions on physicochemical and usable properties of pharmaceutical ointments

The study investigated the effect of chamomile extract obtained in supercritical carbon dioxide conditions on the basic properties of pharmaceutical ointments. A total of five formulations were designed and prepared, differing in the weight ratio of sunflower oil to chamomile extract (5:0, 3.5:1.5, 2.5:2.5, 1.5:3.5 and 0:5). An increase in the concentration of chamomile extract was found to be accompanied by a decrease in hardness, adhesive power and flow limit. Based on viscosity measurements it was shown that ointments containing the hydrophobic plant extract under study were prone to larger drops in viscosity under the effect of the set shear rate. It was determined that from the viewpoint of ointment spreadability and application to the skin, the optimum concentration of chamomile extract for the studied formulations should be within the range of 1.5–2.5%. Furthermore, the addition of chamomile extract to ointments was found to give samples a yellow-green color. Green was observed to be the dominant color, and its saturation and shade varied for different formulations.     

Chronic antidepressant-like effect of EMD386088, a partial 5-HT6 receptor agonist,in olfactory bulbectomy model may be connected with BDNF and/or CREB signalling pathway

Background

The removal of the olfactory bulbs has been attributed to behavioral changes and neuroplasticity manifesting themselves among others like increases in brain neurotrophin expression and neurogenesis. Earlier data presented that EMD386088, a 5-HT₆ receptor partial agonist, exerts antidepressant-like properties after chronic administration in olfactory bulbectomy (OB) model as was it compared with amitriptyline (AMI). The aim of this study was to compare acute and chronic biochemical effects of EMD386088, administered in its antidepressant active (2.5 mg/kg) and non-active (1.25 mg/kg) doses, found in the open field test in OB rats, with those of AMI (10 mg/kg). The levels of 5-HT₆ receptor protein and selected neurotrophins in prefrontal cortex (PFC) and hippocampus (Hp) of rats have been examined.

Effect of long-term administration of ranitidine,a histamine H2 receptor antagonist,on bone metabolism in young growing rats

Background

Histamine regulates function of osteoclasts and osteoblasts, however data regarding the influence of histamine H2 receptors antagonists on bone tissue are ambiguous. Factors that influence growing skeleton may have an important impact on the peak bone mass and future risk of fractures. The aim of our study was the assessment of influence of ranitidine, on growing bones.

Early graft function and intrarenal resistant index after kidney transplantation using Biolasol—A new solid organ preservation fluid

Biolasol is a newly developed preserving solution for cold organ storage prior to transplantation. To date, only animal model experiments results are available. The aim of this single-center analysis was to summarize the clinical experience concerning the early post-transplant course of kidney grafts preserved with Biolasol in comparison with other preservation solutions. Before transplantation, 173 kidney grafts were preserved using Biolasol and 240 organs with other solutions (University of Wisconsin—UW, Institute Georges Lopez—IGL-1, or StoreProtect Plus solutions). Early graft function was defined based on serum creatinine concentration at day 3 (<3 mg/dL—immediate graft function, IGF or >3 mg/dL—slow graft function, SGF) or the need of dialysis therapy during first post-operative week (delayed graft function, DGF). The analysis included intrarenal resistive indices measured by Doppler sonography early after transplantation and before discharge from the hospital. IGF was more frequent in patients with organs preserved with IGL-1 (33.5%) and StoreProtect Plus (38.8%) than Biolasol (18.5%), whereas there was no difference in the occurrence of DGF. Both initial and discharge median resistance index values were significantly higher in the Biolasol subgroup (0.77 and 0.75) than in all three other subgroups (P values for all comparisons <.001), also after 1:1 propensity score matching for baseline characteristics. Multiple logistic regression analysis based on the propensity score-matched cohort revealed that the use of Biolasol solution [OR 0.59 (0.35-0.98); P < .05] independently decreased the occurrence of IGF. In our single-center clinical experience, kidney preservation using Biolasol solution was associated with significantly higher intrarenal resistant index in comparison with other preservation fluids, as well as worse early graft function than in the IGL-1 and the StoreProtect Plus subgroups. Long-term follow-up is needed in order to assess the kidney graft and patient survival.     

Poor Outcomes After Liver Transplantation in Patients With Incidental Cholangiocarcinoma Irrespective of Tumor Localization

Introduction

After liver transplantation for cholangiocarcinoma (CCC), patients have a poor prognosis without use of specific therapeutic strategies. Accordingly, recipients with incidental CCC might have the highest risk of recurrent disease; however, sparse data on the long-term outcome of unselected patients with incidental CCC have been published. The aim of this study was to evaluate the post-transplantation outcomes of patients with incidental CCC with special focus on tumor localization.

Material and Methods

There were 11 primary liver transplantations in patients with incidental CCC of 1310 liver transplantation procedures performed between December 1994 and August 2013. All patients with incidental CCC received a chemotherapy regiment including gemcitabine/5 fluorouracil, doxorubicin, and mitomycin. The patients were switched from calcineurin inhibitors to mammalian target of rapamycin inhibitor−based immunosuppression shortly after CCC diagnosis.

Results

Intra- and extrahepatic tumors were found in 6 and 5 patients, respectively. At median follow-up examination of 26.3 months there were 8 CCC recurrences and 7 patient deaths. Overall survival after liver transplantation for incidental CCC was 88.9% at 1 year, 44.4% at 2 years, and 14.8% at 3 years. The corresponding rates of recurrence-free survival were 45.7%, 45.7%, and 0.0%, respectively. Post-transplantation CCC recurrences were universal with 0% 3-year recurrence-free survival both in patients with intra- and extrahepatic tumors (P = .475).

Conclusions

Incidental CCC in liver transplantation is associated with poor outcomes irrespective of tumor localization. Introduction of new adjuvant multimodal treatment concepts is necessary to improve the prognosis for this subgroup of patients.     

Analysis of the Selected Biochemical Parameters of Liver and Kidney Function in Children of Mothers After Liver Transplantation

Introduction

Children of mothers after liver transplantation (LT) are exposed during fetal life to the immunosuppressive agents. These drugs may have hepatotoxic and nephrotoxic effects.

Objectives

The aim of the work was to assess liver and kidney parameters of children born from mothers who had LT.

Materials and Methods

The research included 51 children of mothers after LT and 51 children from a control group who were born in the First Department of Obstetrics and Gynecology in Warsaw between 2001 and 2013. The control group consisted of children born in the similar gestational age. Analysis concerned neonates, infants, and children older than 12 months. Two liver parameters (alanine transaminase [ALT] and aspartate transaminase [AST]) as well as two kidney parameters (urea and creatinine) were assessed. For statistical analysis we used Fisher's exact test and the Mann-Whitney test.

Results

All children from the LT group had correct ALT levels. In the control group, 5 of 51 cases (9.8 %) had levels that were greater than the norm, and those cases concerned only children younger than 12 months. The average concentration of ALT in the LT group was 15.14 U/L and the average for the control group was 22.6 U/L (P = .012699, Mann-Whitney test). Three of 51 children in the LT group (5.9%) and 8 of 51 (15.7%) in the control group had AST levels that were increased (P = .2003; Fisher's exact test). Incorrect AST levels were reported in all age groups. Incorrect values of kidney parameters concerned only neonates. Increased creatinine levels were reported in 3 of 51 cases (5.9%) in the LT group and in 1 of 51 cases (1.96%) in the control group (P = .6175; Fisher's exact test). The average concentration of creatinine in children of mothers after LT was 0.51 mg/dL, and the average of the control group was 0.44 mg/dL (P = .223698; Mann-Whitney test). Only 1 of 51 children in the LT group (1.96%) had an increased urea level. All children from both the LT and the control groups had normal ultrasound images of urinary tract and liver.

Conclusion

Exposure to immunosuppressive drugs during fetal life does not result in the occurrence of serious disturbances of liver function and kidneys function in children of mothers after LT.     

Effects of second-generation antipsychotics on selected markers of one-carbon metabolism and metabolic syndrome components in first-episode schizophrenia patients

Purpose

Alterations in one-carbon metabolism (OCM) have been repeatedly reported in schizophrenia. However, there is a scarcity of studies addressing the effects of antipsychotics on selected OCM markers in schizophrenia and provided results are inconsistent.

Methods

We recruited 39 first-episode schizophrenia (FES) patients and determined serum profile of total homocysteine (tHcy), folate, vitamin B12, lipoproteins and glucose at baseline and after 12 weeks of treatment with second-generation antipsychotics (SGA) including olanzapine and risperidone in monotherapy.

Results

After 12 weeks of treatment, all patients had significantly higher body mass index (BMI), serum levels of total cholesterol (TC), low-density lipoproteins (LDL), triglycerides (TG) and tHcy together with significantly lower levels of folate and vitamin B12. The analysis of differences between SGA revealed the same biochemical alterations in patients treated with olanzapine as in the whole group, while those receiving risperidone had no statistically significant changes in serum folate, vitamin B12 and TG. There was a significantly higher increase in BMI and TC in patients treated with olanzapine in comparison with those treated with risperidone. Patients receiving olanzapine had a higher decrease in vitamin B12 than those assigned to the treatment with risperidone. Changes in folate, vitamin B12, tHcy and TC levels were significant only in males, even after Bonferroni correction. Multiple regression analysis revealed that changes in tHcy levels are associated with gender and baseline metabolic parameters (BMI, glucose, TC, LDL and HDL) but not with selected SGA.

Conclusions

These results indicate that SGA may influence OCM, especially in first-episode schizophrenia (FES) males.     

Magnetic Resonance Microscopy for Assessment of Morphological Changes in Hydrating Hydroxypropylmethylcellulose Matrix Tablets In Situ–Is it Possible to Detect Phenomena Related to Drug Dissolution Within the Hydrated Matrices?

Purpose

So far, the hydrated part of the HPMC matrix has commonly been denoted as a “gel” or “pseudogel” layer. No MRI-based results have been published regarding observation of internal phenomena related to drug dissolution inside swelling polymeric matrices during hydration. The purpose of the study was to detect such phenomena.

Methods

Multiparametric, spatially and temporally resolved T₂ MR relaxometry, in situ, was applied to study formation of the hydration progress in HPMC matrix tablets loaded with L-dopa and ketoprofen using a 11.7 T MRI system. Two spin-echo based pulse sequences were used, one of them specifically designed to study short T₂ signals.

Results

Two components in the T₂ decay envelope were estimated and spatial distributions of their parameters, i.e. amplitudes and T₂ values, were obtained. Based on the data, different region formation patterns (i.e. multilayer structure) were registered depending on drug presence and solubility. Inside the matrix with incorporated sparingly soluble drug a specific layer formation due to drug dissolution was detected, whereas a matrix with very slightly soluble drug does not form distinct external “gel-like” layer.

Conclusions

We have introduced a new paradigm in the characterization of hydrating matrices using ¹H MRI methods. It reflects molecular mobility and concentration of water inside the hydrated matrix. For the first time, drug dissolution related phenomena, i.e. particular front and region formation, were observed by MRI methods.