Supplementation with Octacosanol Affects the Level of PCSK9 and Restore Its Physiologic Relation with LDL-C in Patients on Chronic Statin Therapy

Dietary supplementation with sugar cane derivates may modulate low-density lipoprotein cholesterol (LDL-C) and proprotein convertase subtilisin/kexin type 9 (PCSK9) levels. The purpose of this study was to determine if dietary supplement (DS), containing Octacosanol (20 mg) and vitamin K2 (45 µg), could restore the disrupted physiologic relation between LDL-C and serum PCSK9. Double-blind, randomized, placebo-controlled, single-center study including 87 patients on chronic atorvastatin therapy was conducted. Eighty-seven patients were randomized to receive DS (n = 42) or placebo (n = 45), and followed for 13 weeks. Serum PCSK9 levels, lipid parameters and their relationship were the main efficacy endpoints. The absolute levels of PCSK9 and LDL-C were not significantly different from baseline to 13 weeks. However, physiologic correlation between % change of PCSK9 and % change of LDL-C levels was normalized only in the group of patients treated with DS (r = 0.409, p = 0.012). This study shows that DS can restore statin disrupted physiologic positive correlation between PCSK9 and LDL-C. Elevated PCSK9 level is an independent risk factor so controlling its rise by statins may be important in prevention of cardiovascular events.     

Hepatoprotective Effect of Mixture of Dipropyl Polysulfides in Concanavalin A-Induced Hepatitis

The main biologically active components of plants belonging to the genus Allium, responsible for their biological activities, including anti-inflammatory, antioxidant and immunomodulatory, are organosulfur compounds. The aim of this study was to synthetize the mixture of dipropyl polysulfides (DPPS) and to test their biological activity in acute hepatitis. C57BL/6 mice were administered orally with DPPS 6 h before intravenous injection of Concanavalin A (ConA). Liver inflammation, necrosis and hepatocytes apoptosis were determined by histological analyses. Cytokines in liver tissue were determined by ELISA, expression of adhesive molecules and enzymes by RT PCR, while liver mononuclear cells were analyzed by flow cytometry. DPPS pretreatment significantly attenuated liver inflammation and injury, as evidenced by biochemical and histopathological observations. In DPPS-pretreated mice, messenger RNA levels of adhesion molecules and NADPH oxidase complex were significantly reduced, while the expression of SOD enzymes was enhanced. DPPS pretreatment decreased protein level of inflammatory cytokines and increased percentage of T regulatory cells in the livers of ConA mice. DPPS showed hepatoprotective effects in ConA-induced hepatitis, characterized by attenuation of inflammation and affection of Th17/Treg balance in favor of T regulatory cells and implicating potential therapeutic usage of DPPS mixture in inflammatory liver diseases.     

Semen analysis and treatment risk factors in long-term survivors of childhood cancer

The objective of this study was to compare semen quality (sperm density, progressive motility and spermia) between long-term childhood cancer survivors and a control group of males. The second objective was to correlate the semen analysis of the survivors with cancer treatment and endocrine status. The semen quality of 143 survivors (median age, 23.6 years) was compared to 200 men (median age, 27.9 years) who had not been diagnosed with cancer. The cancer-related risk factors and gonadotrophin levels were compared. Overall, 65% of the survivors had abnormal semen analysis compared to 26.5% of the controls (p < 0.0001). Survivors with nonaspermia had lower sperm density than the controls (p < 0.001). Other observed correlations were not significant. Survivors who were treated with alkylating agents were more likely to have abnormal semen analysis (p < 0.008). Follicle-stimulating hormone and luteinising hormone levels were significantly elevated (p < 0.0001) in survivors with abnormal semen analysis. The semen quality parameters, except for low sperm density, did not differ in survivors with nonaspermia compared to the controls. The risk factors included treatment with alkylating agents. Elevated gonadotrophin levels correlated with abnormal semen analysis. All cancer survivors should be made aware of the possibility of suffering from cancer treatment-related infertility.     

Cystoid macular edema in anterior chamber lens implantation following posterior capsule rupture

By comparing the incidence of cystoid macular edema (CME) in three groups of patients having different surgical procedures, we attempted to assess the role of vitreous loss as a risk factor for CME development. In the first group (n = 470), the surgical procedure was extracapsular cataract extraction followed by implantation of posterior chamber lens (EC-CE + PC-IOL). The second group (n = 42) had extracapsular cataract extraction which was complicated by posterior capsule rupture, and therefore anterior vitrectomy followed by implantation of anterior chamber lens had to be performed (ECCE + anterior vitrectomy + AC-IOL). In the third group (n = 22) the surgery was intracapsular cataract extraction followed by anterior chamber lens implantation (ICCE + AC-IOL). The third group was included in this follow up study to assess the role of AC-IOL as a possible causative factor for development of CME in uncomplicated cases of ICCE and AC-IOL. The difference of incidences of CME in the second and third group would therefore depend mostly on the vitreous loss. The incidence of CME diagnosed by fluorescein angiography in the first, second and third group was 1.5% (7/470), 35.7% (15/42) and 9.0% (2/22), respectively. All patients who developed CME were treated with combination of corticosteroid-antibiotic drops, dexamethasone retrobulbarly (40 mg/day) and peroral indomethacine (25 mg/day/6 weeks). This therapeutic regime resulted in only moderate improvement of visual acuity.Abbreviations AC-IOL anterior chamber intraocular lens - CME cystoid macular edema - ECCE extracapsular cataract extraction - ICCE intracapsular cataract extraction - IOL intraocular lens - PC-IOL posterior chamber intraocular lens     

Amphiphilic star-like macromolecules as novel carriers for topical delivery of nonsteroidal anti-inflammatory drugs

The objective of this study was to evaluate amphiphilic star-like macromolecules (ASMs) as a topical drug delivery system. Indomethacin, piroxicam, and ketoprofen were individually encapsulated into the ASMs using coprecipitation. The effects of the ASMs on percutaneous permeation of nonsteroidal anti-inflammatory drugs (NSAIDs) across full thickness, hairless mouse skin were evaluated in vitro using modified Franz diffusion cells. In addition, solubility and in vitro release experiments were performed to characterize ASMs behavior in aqueous media. Poly(ethylene glycol) (PEG) and Pluronic P-85 were used as polymer controls to compare the role of PEG and amphiphilic behavior in the ASMs. In vitro release experiments indicated that ASMs can delay drug release (P⋖05), whereas solubility measurements showed that ASMs can increase NSAIDs aqueous solubility (P⋖05). Percutaneous permeation studies revealed that ASMs decreased both flux and Q₂₄ of drugs compared with the control (P⋖10). Skin pretreatment studies with ASM-containing solution before drug application demonstrated that pretreatment similarly influenced NSAID percutaneous permeation. In conclusion, ASMs likely slow drug permeation through 2 mechanisms, delayed drug diffusion from its core and skin dehydration by its shell. Thus, ASMs may be useful for delayed dermal delivery or prevention of compound permeation through the skin (eg, sunscreens, N,N-diethyl-m-toluamide [DEET]) from aqueous formulations.     

Effects of Posttraumatic Stress and Acculturation on Marital Functioning in Bosnian Refugee Couples

Forty Bosnian refugee couples living in the United States completed a translated version of the PTSD Symptom Scale—Self Report, the Behavioral Acculturation Scale, the Marital Satisfaction Inventory—Revised, and a demographic questionnaire. Posttraumatic stress disorder (PTSD) symptomatology was the best predictor of marital functioning and was related negatively to acculturation. After controlling for PTSD, acculturation did not predict marital functioning. Wives' marital satisfaction was best predicted by husbands' PTSD, husbands' acculturation, and their own PTSD. Husbands' marital satisfaction was not predicted significantly by any of these variables. These findings suggest several implications for mental health professionals dealing with refugees and other traumatized populations.     

The slow and infraslow oscillations of cortical neural network

ObjectiveIn this study we investigated the properties of infraslow oscillations (ISOs) ?0.05 Hz and delta frequency band in the patients during the epileptic discharges and in healthy persons who performed a variety of mental and physical tasks.MethodsThe EEG signals were recorded on the subjects who were divided into three groups. In the first group were patients with global epileptic seizures, while in the second group were patients with focal epileptic seizures. In the third group were healthy volunteers who performed different mental and physical tasks.ResultsBy analyzing EEG data of epileptic patients, we showed that frequency peak exists at 1.5 Hz which is typical for general and focal epileptic seizures. In the type of general epileptic discharges the role of the slow rhythms at 0.05 Hz, was particularly pronounced and their origin was in fluctuations of cortical neural network. The properties of parameter spectral coherency of ISOs in healthy persons point to their important role in brain functioning.ConclusionsOur results suggested that the role of ISOs could be extended, because they were detected in healthy human subjects during carrying out different tasks. Investigating the properties of parameter spectral coherency, we showed that in this case correlation between different regions of the brain was significantly modulated with ISOs.     

Cuprizone [Bis(Cyclohexylidenehydrazide)] is Selectively Toxic for Mature Oligodendrocytes

Cuprizone [bis(cyclohexylidenehydrazide)]-induced toxic demyelination is an experimental animal model commonly used to study de- and remyelination in the central nervous system. In this model, mice are fed with the copper chelator cuprizone which leads to oligodendrocyte death with subsequent demyelination. The underlying mechanisms of cuprizone-induced oligodendrocyte death are still unknown, and appropriate in vitro investigations to study these mechanisms are not available. Thus, we studied cuprizone effects on rat primary glial cell cultures and on the neuroblastoma cell line SH-SY5Y. Treatment of cells with different concentrations of cuprizone failed to show effects on the proliferation and survival of SH-SY5Y cells, microglia, astrocytes, and oligodendrocyte precursor cells (OPC). In contrast, differentiated mature oligodendrocytes (OL) were found to be significantly affected by cuprizone treatment. This was accompanied by a reduced mitochondrial potential in cuprizone-treated OL. These results demonstrate that the main toxic target for cuprizone is mature OL, whilst other glial cells including OPC are not or only marginally affected. This explains the selective demyelination induced by cuprizone in vivo.