VITamin D and OmegA-3 TriaL (VITAL) bone health ancillary study: clinical factors associated with trabecular bone score in women and men.

We investigated the association of clinical variables with TBS at baseline in the bone health sub-cohort of the VITamin D and OmegA-3 TriaL (VITAL). Lower TBS was associated with female sex, aging, BMI ≥ 25 kg/m2, SSRI use, high alcohol intake, and presence of diabetes; there was a trend towards significance between lower TBS and history of fragility fractures. INTRODUCTION: We investigated whether TBS differs by sex, race, body mass index (BMI), and other clinical variables. METHODS: The VITamin D and OmegA-3 TriaL (VITAL) is determining effects of vitamin D3 and/or omega-3 fatty acid (FA) supplements in reducing risks of cancer and cardiovascular disease. In the VITAL: Effects on Bone Structure/Architecture ancillary study, effects of these interventions on bone will be investigated. Here, we examine the associations of clinical risk factors with TBS assessments at baseline in the bone health sub-cohort, comprised of 672 participants (369 men and 303 women), mean (± SD) age 63.5 ± 6.0 years; BMI ≤ 37 kg/m2, no bisphosphonates within 2 years or other bone active medications within 1 year. RESULTS: TBS was greater in men than women (1.311 vs. 1.278, P < 0.001) and lower with elevated BMIs (P < 0.001), higher age (P = 0.004), diabetes (P = 0.008), SSRI use (P = 0.044), and high alcohol intake (P = 0.009). There was a trend for history of fragility fractures (P = 0.072), and lower TBS. TBS did not vary when analyzed by race, smoking, history of falls, and multivitamin or caffeine use. CONCLUSIONS: Lower TBS was associated with female sex, aging, BMI ≥ 25 kg/m2, SSRI use, alcohol use, and presence of diabetes; there was a trend between lower TBS and history of fragility fractures. TBS may be useful clinically to assess structural changes that may be associated with fractures among patients who are overweight or obese, those on SSRIs, or with diabetes. Ongoing follow-up studies will clarify the effects of supplemental vitamin D3 and/or FA's on TBS and other bone health measures. TRIAL REGISTRATION: NCT01747447.

Intraspecific relationship analysis by DNA markers and in vitro cytotoxic and antioxidant activity in Eleutherococcus senticosus.

To analyse genetic relationships and intraspecific variation within Eleutherococcus senticosus, the polymerase chain reaction (PCR) was performed on total genomic DNAs of 10 Eleutherococcus collections. Ten primers were used for amplification, yielding 106 bands, of which 87 were polymorphic. The genetic diversity and genetic distance among 10 collections of Eleutherococcus species were used to describe the dendrogram showing the phylogenic relationship. The 10 collections were classified into two groups (groups I and II) at a similarity coefficient of 0.50. Group I included E. senticosus from Bukhaedo (Japan), E. sessliliflorus from Youngwal (Korea), E. seoulense and E. chiisanesis, while group II included several internal and Russian collections. The range of polymorphism was from 66.7 to 90.9% in the 87 amplified polymorphic DNA fragments. The similarity value of all collections ranged from 0.41 to 0.92, and the average genetic distance was 0.61. Thus, RAPD analysis was useful in determining genetic relatedness among collections and in identifying different genotypes of E. senticosus and other Eleutherococcus species. Also, the biological activity on DPPH radical scavenging, antilipid peroxidation in rat liver microsomes and cytotoxic sulforhodamine B (SRB) assay was evaluated using root extracts of E. senticosus, Odaesan, Korea. Ethyl acetate and n-butanol fractionation revealed strong antioxidant against scavenging on DPPH free radical and also ethyl acetate fractionation exhibited high antilipid peroxidative activities. In the cytotoxic effects were evaluated on seven human cancer cell lines, the values of 50% growth inhibition (GI(50)) were mostly below 30 microg/ml for crude extracts to be considered as significantly active.

Combination therapy with fluconazole and flucytosine in the murine model of cryptococcal meningitis.

This study elucidates the role of combined fluconazole and flucytosine as therapy for cryptococcosis in the murine model of meningitis. Three strains of Cryptococcus neoformans for which the range of fluconazole MICs was wide--2 microg/ml (susceptible strain), 8 microg/ml (moderately susceptible strain), and 32 microg/ml (resistant strain)--were used for infection. One day postinfection, the mice were randomized into eight treatment groups: placebo; flucytosine (40 mg/kg of body weight/day); fluconazole at 3 mg/kg/day (low dosage), 10 mg/kg/day (moderate dosage), or 20 mg/kg/day (high dosage); and combined flucytosine and fluconazole at low, moderate, or high doses of fluconazole. Three major findings were demonstrated: (i) correlation between the MICs for the isolates and the in vivo effectiveness of fluconazole as assessed by the reduction in cryptococcal brain burden, (ii) a dose-response curve (a higher dose of fluconazole was significantly more efficacious than a lower dose [P < 0.001]), and (iii) synergism between fluconazole and flucytosine (therapy with a combination of fluconazole and flucytosine was superior to therapy with either agent alone [P < 0.01]).

The mouse DNA binding protein Rc for the kappa B motif of transcription and for the V(D)J recombination signal sequences contains composite DNA-protein interaction domains and belongs to a new family of large transcriptional proteins.

Rc is a DNA binding protein with dual specificities for the V(D)J recombination signal sequences and for the B motif of the immunoglobulin kappa chain gene enhancer. The largest Rc transcript present in lymphoid cells/tissues is approximately 9 kb. Molecular cloning and sequence determination for 8822 bp of mouse Rc cDNA revealed an open reading frame of 2282 amino acids and long 5'- and 3'-untranslated regions. The derived amino acid sequence contains multiple DNA and protein interaction domains. Composite ZAS structures with tandem zinc fingers, an acidic motif, and a Ser/Thr-rich segment are located near the N-terminal and the C-terminal regions. The middle region of Rc contains a lone zinc finger, an acidic motif, a Ser-rich region, a nucleus localization signal, and GTPase motifs. Cloning and characterization of a mouse Rc gene show that the Rc cDNA corresponds to seven exons located in a genomic region spanning 70 kb. Exon 2 is exceptionally large, with 5487 bp. cDNA cloning and Northern blot analyses revealed multiple Rc transcripts, probably generated by alternative splicings. Sequence comparisons show that Rc belongs to a ZAS protein family that is involved in gene transcription and/or DNA recombination. The major histocompatibility complex class I gene enhancer binding proteins MBP1 and MBP2 are other representatives of this ZAS protein family.