Activities of naphthylisoquinoline alkaloids and synthetic analogs against Leishmania major

The current treatments for leishmaniasis are unsatisfactory due to their toxic side effects, high costs, and increasing problems with drug resistance. Thus, there is an urgent need for alternative drugs against leishmaniasis. Different approaches have been used to identify novel pharmacophores against Leishmania sp. parasites, and one strategy has been the analysis of naturally occurring plant-derived compounds, including naphthylisoquinoline alkaloids. In the present study, we examined the abilities of these alkaloids to inhibit the growth of Leishmania major promastigotes and evaluated their effects on macrophages, dendritic cells, and fibroblasts. Furthermore, we determined the efficacy of selected compounds in decreasing the infection rate of macrophages and regulating their production of cytokines and nitric oxide. Our results demonstrate that the naphthylisoquinoline alkaloids ancistrocladiniums A and B (compounds 10 and 11) and the synthetic isoquinolinium salt (compound 14) were effective against intracellular amastigotes in the low submicromolar range, while toxicity against mammalian cells was observed at concentrations that were significantly higher than those needed to impair parasite replication. The activities of compounds 11 and 14 were mainly directed against the amastigote stage of L. major. This effect was not associated with the stimulation of host macrophages to produce nitric oxide or secrete cytokines relevant for the leishmanicidal function. In conclusion, our data suggest that ancistrocladiniums A and B (compounds 10 and 11) and the synthetically prepared isoquinolinium salt (compound 14) are promising candidates to be considered as lead compounds for leishmanicidal drugs.     

Trans Fatty Acids in Human Milk in Latvia: Association with Dietary Habits during the Lactation Period

The human milk fatty acid, including trans fatty acid, composition is predominantly affected by the maternal diet. The aim of this research was to determine the trans fatty acid level in human milk among lactating women in Latvia, and to evaluate how maternal dietary habits affect the trans fatty acid composition of human milk. In total, 70 lactating women participated in this cross-sectional study. A 72-hour food diary and food frequency questionnaire were used to evaluate maternal dietary habits. Different trans fatty acids in human milk samples were determined using gas chromatography (Agilent 6890N, Agilent Technologies Incorporated, the United States). Overall, the dietary intake of trans fatty acids among the participants was 0.54 ± 0.79 g per day. The total trans fatty acid level in the human milk samples was 2.30% ± 0.60%. The composition of trans fatty acids found in human milk was associated with maternal dietary habits. Higher elaidic acid, vaccenic acid and total trans fatty acid levels in human milk were found among participants with a higher milk and dairy product intake. Meat and meat product intake were associated with a higher vaccenic acid and total trans fatty acid levels in human milk. A moderate association was also established between maternal trans fatty acid intake and the total trans fatty acid level in human milk. The obtained correlations indicate that maternal dietary habits during lactation can impact the composition of trans fatty acids found in human milk.     

Outcome of infants with inflicted traumatic brain injury (shaken baby syndrome) in Estonia

This is a population-based prospective study to identify the long-term outcome of children with inflicted traumatic brain injury (ITBI). Twenty-two survivors were identified and followed up. Only 2 of 22 had no developmental problems at follow-up, 20 of 22 children were having different developmental problems, among them 3 of 22 were severely handicapped. Psychological tests passed 17 of 22, 5 did not pass due to severe handicap (3 children) or were too young (2 patients). Epilepsy was found in 7 of 22, being intractable in 3 cases. Serious motor problems were identified in 5 of 22. Ophthalmologic problems were found in 4 of 22. The most important predictor of adverse outcome was young age at the time of the insult. Conclusion: the outcome of these potentially healthy children is poor. The key question is prevention. Health care professionals should be more concerned about these problems.     

High cardiovascular fitness is associated with low metabolic risk score in children: the European Youth Heart Study

The aim of the present study was to examine the associations of cardiovascular fitness (CVF) with a clustering of metabolic risk factors in children, and to examine whether there is a CVF level associated with a low metabolic risk. CVF was estimated by a maximal ergometer bike test on 873 randomly selected children from Sweden and Estonia. Additional measured outcomes included fasting insulin, glucose, triglycerides, HDLC, blood pressure, and the sum of five skinfolds. A metabolic risk score was computed as the mean of the standardized outcomes scores. A risk score <75th percentile was considered to indicate a low metabolic risk. CVF was negatively associated with clustering of metabolic risk factors in children. Receiver operating characteristic curve analysis showed a significant discriminatory accuracy of CVF in identifying the low/high metabolic risk in girls and boys (p < 0.001). The CVF level for a low metabolic risk was 37.0 and 42.1 mL/kg/min in girls and boys, respectively. These levels are similar to the health-related threshold values of CVF suggested by worldwide recognized organizations. In conclusion, the results suggest a hypothetical CVF level for having a low metabolic risk, which should be further tested in longitudinal and/or intervention studies.     

Transarterial chemoembolization in patients not eligible for liver transplantation: single-center results

OBJECTIVE: The purpose of this study was to evaluate the effectiveness of transarterial chemoembolization in the care of patients not eligible for liver transplantation. CONCLUSIONS: Prognosis depends on local response, Okuda score, alpha-fetoprotein level, and tumor size and is independent of the presence of portal venous thrombosis.     

Gamma Knife radiosurgery as a primary treatment option for solitary brain metastases from ovarian carcinoma

We present three patients with brain metastasis cases from ovarian carcinoma (BMOC) treated at William Beaumont Hospital with a median follwow-up of 77 months and a mean survival after brain involvement of 23.66 months (range 5–44). Clinical and physical aspects are presented. Between December 2006 and August 2008, three cases of BMOC were treated using Gamma Knife (GK) radiosurgery. All patients had FIGO Stage III primary disease at initial diagnosis. Treatment sequences and features are described. GK achieves excellent local control of BMOC. Other parameters could be considered as biologically effective.     

HIV-serology and lymphocyte subsets in relation to therapy and clinical development in haemophiliacs

389 Swedish patients with haemophilia A, B or von Willebrand's disease were examined for HIV-1 antibodies. T-cell subsets were measured in 260 of them. HIV-1 antibodies were found in 98 of these patients. Of the 199 patients with severe or moderate haemophilia A, 44% were seropositive. They had seroconverted between 1979 and 1983. HIV-1-seropositive patients had significantly decreased numbers of CD4 cells and increased numbers of CD8 cells. The seronegative haemophilia A patients had significantly increased numbers of CD8 cells. The T-cell subsets were followed for a median of 40 months in 73 seropositive patients. All groups of patients, at different clinical stages, showed decreasing numbers of CD4 cells. The most pronounced decrease was seen in the patients who developed AIDS, followed by the group which developed HIV-related signs or symptoms. HIV antigen in serum and antibody pattern in Western blot and ELISA were followed in 89 patients. HIV-1 antigen was present and p24 antibodies were lacking in 11% and 13% of asymptomatic subjects, in 13% and 20% of patients with persistent generalized lymphadenopathy, in 33% and 38% of patients with other HIV-related signs or symptoms and in 5/6 of the AIDS patients, respectively. In conclusion, the decrease of CD4 cells and the presence of HIV antigen and/or absence of p24 antibodies were found to be prognostic markers for HIV disease.     

A new tetra-plex fluorimetric assay for the quantification of cerebrospinal fluid β-amyloid42, total-tau,phospho-tau and α-synuclein in the differential diagnosis of neurodegenerative dementia

Journal of Neurology - Differential diagnosis of neurodegenerative dementia is currently supported by biomarkers including cerebrospinal fluid (CSF) tests. Among them, CSF total-tau (t-tau),...