Influence of propafenone on the anticonvulsant activity of various novel antiepileptic drugs in the mouse maximal electroshock model

Background

The main mechanism of action of propafenone (antiarrhythmic drug) involves the inhibition of the fast inward sodium current during phase 0 of the action potential. Sodium channel-blocking activity is also characteristic for some antiepileptic drugs. Therefore, it could be assumed that propafenone may also affect seizures. In the present study, we evaluated the effect of propafenone on the protective effect of oxcarbazepine, lamotrigine, topiramate and pregabalin against the maximal electroshock-induced seizures in mice.

The Impact of Gelatin on the Pharmaceutical Characteristics of Fucoidan Microspheres with Posaconazole

Fungal infections and invasive mycoses, despite the continuous medicine progress, are an important globally therapeutic problem. Multicompartment dosage formulations (e.g., microparticles) ensure a short drug diffusion way and high surface area of drug release, which as a consequence can provide improvement of therapeutic efficiency compared to the traditional drug dosage forms. As fucoidan is promising component with wide biological activity per se, the aim of this study was to prepare fucospheres (fucoidan microparticles) and fucoidan/gelatin microparticles with posaconazole using the one-step spray-drying technique. Pharmaceutical properties of designed fucospheres and the impact of the gelatin addition on their characteristics were evaluated. An important stage of this research was in vitro evaluation of antifungal activity of developed microparticles using different Candida species. It was observed that gelatin presence in microparticles significantly improved swelling capacity and mucoadhesiveness, and provided a sustained POS release. Furthermore, it was shown that gelatin addition enhanced antifungal activity of microparticles against tested Candida spp. strains. Microparticles formulation GF6, prepared by the spray drying of 20% fucoidan, 5% gelatin and 10% Posaconazole, were characterized by optimal mucoadhesive properties, high drug loading and the most sustained drug release (after 8 h 65.34 ± 4.10% and 33.81 ± 5.58% of posaconazole was dissolved in simulated vaginal fluid pH 4.2 or 0.1 M HCl pH 1.2, respectively).     

Impaired glucose metabolism in colorectal cancer

OBJECTIVE: Some studies have found that people with type 2 diabetes mellitus are at increased risk of neoplasms, especially colorectal cancer (CRC). In other studies it is also suggested that there is a higher incidence of diabetes mellitus in patients with CRC. The aims of this study were to assess whether the incidence of type 2 diabetes mellitus and impaired glucose tolerance (IGT) are higher in subjects with CRC and to determine the difference between diabetic subjects and healthy controls regarding glucose metabolism (glycaemia, insulinaemia, serum levels of C-peptide) as well as insulin resistance and sensitivity. MATERIAL AND METHODS: The study included a total of 80 subjects: 40 enrolled patients (20 M, 20 F) with newly diagnosed sporadic colorectal cancer and 40 subjects with endoscopically excluded CRC or adenomas serving as controls. Subjects were matched for gender, age and body mass index (BMI) (age +/- 5 years BMI +/- 1 kg/m2). A 75-g oral glucose tolerance test was performed after an overnight fast. Samples for glycaemia, serum levels of C-peptide and insulin were taken at 0, 30, 60, 90, 120 and 150 min of the study. HOMA-IR, EIR, EIR/HOMA-IR indexes were calculated. RESULTS: There was a significantly higher incidence of impaired glucose metabolism (IGM-diabetes mellitus or IGT) in CRC subjects. No differences were found in levels of glucose, insulin or C-peptide. Insulinaemia and C-peptide curves showed a shift typical of diabetes, in the form of a delayed insulin release peak. The HOMA-IR, EIR as well as the EIR/HOMA-IR indexes showed no differences between groups. CONCLUSIONS: A significantly higher incidence of IGM appears to occur in CRC patients than in the healthy population. This phenomenon is not dependent on age and body-weight, which may suggest that it is cancer that predisposes to diabetes rather than the other way round. The neoplastic process in the colon is not associated with hyperinsulinaemia or insulin resistance, but in CRC patients, pancreatic B-cell dysfunction typical of the early stages of diabetes is seen.     

Effect of Low-Immunogenic Yogurt Drinks and Probiotic Bacteria on Immunoreactivity of Cow’s Milk Proteins and Tolerance Induction—In Vitro and In Vivo Studies

There is no effective therapy for milk allergy. The role of lactic acid bacteria (LAB) and probiotics in protection against allergy-related outcomes is still under investigation. The aim of the study was to evaluate the immunomodulative and therapeutic potential of yogurt drinks in cow’s milk allergy (CMA) management. We compared immunoreactivity of α-casein (α-CN), β-casein (β-CN), κ-casein (κ-CN), α-lactalbumin (α-LA), and β-lactoglobulin (β-LG) in 27 yogurt drinks fermented with different basic yogurt cultures, or yogurt cultures enriched with Lactobacillus plantarum and/or Bifidobacterium lactis strains, by competitive ELISA assay. Drinks with the lowest antigenic potential were used as allergoids for CMA therapy. BALB/c mice were sensitized via intraperitoneal injection of α-CN + β-LG mixture with aluminum adjuvant, and gavaged with increasing doses of selected low-immunogenic drinks (YM—basic, or YM-LB—enriched with L. plantarum and B. lactis) to induce tolerance. Milk- or phosphate-buffered saline (PBS)-dosed mice served as controls. Compared to milk, the immunoreactivity of proteins in drinks increased or decreased, depending on the bacterial sets applied for fermentation. Only a few sets acted synergistically in reducing immunoreactivity. The selected low-immunogenic drinks stimulated allergic mice for profiling Th2 to Th1 response and acquire tolerance, and the effect was greater with YM-LB drink, which during long-lasting interventional feeding strongly increased the secretion of regulatory cytokines, i.e., IL-10 and TGF-β, and IgA and decreased IL-4, IgE, and anti-(α-CN + β-LG) IgG₁. The studies revealed variations in the potency of yogurt bacteria to change allergenicity of milk proteins and the need for their strict selection to obtain a safe product for allergy sufferers. The YM-LB drink with reduced antigenic potential may be a source of allergoids used in the immunotherapy of IgE mediated CMA, but further clinical or volunteer studies are required.     

Pathomorphological features of acute rejection in patients after orthotopic liver transplantation: own experience

INTRODUCTION: Acute hepatic allograft rejection remains an important problem following liver transplantation. Liver biopsy specimens show a combination of characteristic changes, first observed by Snover as a diagnostic triad: portal inflammation, bile duct damage, and central or portal vein endothelial inflammation (endothelitis or endothelialitis). The aim of this study was to describe our histopathological assessment of liver transplants. MATERIALS AND METHODS: In the period between September 2000 and June 2004, we evaluated 150 liver biopsy specimens from 105 liver recipients. RESULTS: Acute rejection was diagnosed in 26.6% of liver biopsies taken from 31.4% patients who demonstrated clinical symptoms of liver damage. In 90% of cases the rejection was described as minimal or mild, and in 10% as moderate. There was no episode of severe acute rejection. Only four biopsies (10%) showed nothing but Snover triad changes. In 9 (22.5%) cases only acute rejection was diagnosed; the remaining showed in addition to acute rejection the possibility of other concomitant pathologies: viral infection in 15 cases (37.5%), biliary flow obstruction in 11 cases (28.5%), functional cholestasis in two cases (5%), and ischemic complications in three cases (7.5%). CONCLUSIONS: Histologically confirmed acute rejection episodes were diagnosed in 14.9% liver recipients. Liver biopsy specimens, aside from Snover triad features, often showed other unspecific morphological changes. Differentiation of acute rejection from other accompanying diseases is sometimes difficult, requiring precise clinical data and pathologist experience.     

Effect of Conjugation of Cow Milk Whey Protein with Polyethylene Glycol on Changes in their Immunoreactive and Allergic Properties

Polyethylene glycol (PEG) was conjugated with milk proteins to determine the changes of the immunoreactive properties of α-lactalbumin (α-la) and β-lactoglobulin (β-lg). The competitive ELISA method was applied to determine the antigenicity of modified protein, using rabbit polyclonal antibodies. The immunoreactivity decreased to 0.90 μg ml-1 α-la (which corresponded with 0.05%) and 0.14 μg ml^-1 β-lg (which corresponded with 0.08% of the immunoreactivity observed in raw milk). The determination of allergenicity of modified whey proteins was carried out on a group of 10 allergic patients and it was insignificantly weaker than that of a control sample of milk allergens.