Antioxidant and antimicrobial actions of the clubmoss <Emphasis Type="Italic">Lycopodium clavatum</Emphasis> L.

Purpose of the present study was to evaluate antioxidant, antibacterial, antifungal, and antiviral activities of the petroleum ether, chloroform, ethyl acetate and methanol extracts as well as the alkaloid fraction of Lycopodium clavatum L. (LC) from Lycopodiaceae growing in Turkey. Antioxidant activity of the LC extracts was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging method at 0.2 mg/ml using microplate-reader assay. Antiviral assessment of LC extracts was evaluated towards the DNA virus Herpes simplex (HSV) and the RNA virus Parainfluenza (PI-3) using Madin-Darby Bovine Kidney (MDBK) and Vero cell lines. Antibacterial and antifungal activities of the extracts were tested against standard and isolated strains of the following bacteria; Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Acinobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus, Bacillus subtilis as well as the fungi; Candida albicans and C. parapsilosis. All of the extracts possessed noteworthy activity against ATCC strain of S. aureus (4 μg/ml), while the LC extracts showed reasonable antifungal effect. On the other hand, we found that only the chloroform extract was active against HSV (16–8 μg/ml), while petroleum ether and alkaloid extracts inhibited potently PI-3 (16–4 μg/ml and 32–4 μg/ml, respectively). However, all of the extracts had insignificant antiradical effect on DPPH. In addition, we also analyzed the content of the alkaloid fraction of the plant by capillary gas chromatography-mass spectrometry (GC-MS) and identified lycopodine as the major alkaloid.     

Integrative analysis of mRNA and microRNA expression profiles in laryngeal squamous cell carcinoma

Larynx cancer is a therapeutically challenging disease. Rapidly evolving experimentally validated data have significantly improved our understanding of the complex role of numerous RNA, DNA, and proteins that play a role in the development and progression of cancer. Based on the insights from approximately two decades of research, it seems clear that microRNAs (miRNAs) have revolutionized our concepts related to the main role of noncoding RNAs in different cancers’ progression, development, and metastasis. Mechanistically, miRNAs have been reported to regulate different RNAs and finally protein-coding genes. The expression profiling of miRNAs and messenger RNA (mRNAs) was conducted for a deeper analysis of the miRNAs and mRNAs which play an essential role in larynx cancer. Downregulation or upregulation over twofolds in the miRNAs was considered to be significant, and that of sixfolds or below was considered to be significant for the mRNAs. In accordance with this approach, the expression levels of 43 miRNAs were increased in this study, whereas the expression levels of 129 were decreased. Accordingly, all the genomic expression studies provided evidence of upregulation of 97 genes, whereas 128 genes were found to be downregulated. Among these miRNAs, hsa-miR-20a-3p and hsa-miR-1972 were noted to be important in the etiology of larynx cancer.     

Total heart volume variation throughout the cardiac cycle in humans

Variations in total heart volume (atria plus ventricles) during a cardiac cycle affect efficiency of cardiac pumping. The goals of this study were to confirm the presence, extent, and contributors of total heart volume variation during the cardiac cycle in healthy volunteers with the use of MRI. Eight healthy volunteers were examined by MRI at rest. Changes in total cardiac volume throughout the cardiac cycle were calculated using the following methods: 1) planimetry derived from gradient-echo cine images and 2) flow-sensitive sequences to quantify flow in all vessels leading to and from the heart. The maximum total heart volume diminished during systole by 8.2 +/- 0.8% (SEM, range 4.8-10.6%) measured by method 1 and 8.8 +/- 1.0% (SEM, range 5.6-11.8%) by method 2 with good agreement between the methods [difference according to Bland-Altman analysis -0.6% +/- 1.0% (SD), intraclass correlation coefficient = 0.999]. This decrease in volume is predominantly explained by variation at the midcardiac level at the widest diameter of the heart with a left-sided predominance. In the short axis of the heart, the change of slice volume was proportional to the end-diastolic slice volume. The present study has confirmed the presence of total heart volume variation that predominantly occurs in the region of atrioventricular plane movement and on the left side. The total heart volume variation may relate to the efficiency of energy use by the heart to minimize displacement of surrounding tissue while accounting for the energy required to draw blood into the atria during ventricular systole.     

Cardiac-specific norepinephrine mass transport and its relationship to left ventricular size and systolic performance

Objectives of this study were to develop a technique for quantifying cardiac-specific norepinephrine (NE) mass transport and determine whether cardiac NE kinetic modeling parameters were related to physiological variables of left ventricular (LV) size and systolic performance in nine patients with chronic mitral regurgitation. Biplane contrast cineventriculograms were used to determine LV size and ejection fraction (EF), micromanometer LV pressures and radionuclide LV volumes from a range of loading conditions to calculate LV end-systolic elastance, and [(3)H]NE infusions with LV and coronary sinus sampling for [(3)H]NE and endogenous NE during and after termination of infusions to model NE mass transport. Total NE release rate into cardiac interstitial fluid (M(IF)(R)) averaged 859 +/- 214 and NE released de novo into cardiac interstitial fluid (M(IF)(u,r,en)) averaged 546 +/- 174 pmol/min. Both M(IF)(R) and M(IF)(u,r,en)correlated directly with LV end-systolic volume (r = 0.84, P = 0.005; r = 0.86, P = 0.003); inversely with LV EFs (r = -0.75, P = 0.02; r = -0.81, P = 0.008); and inversely with LV end-systolic elastance values, optimally fit by a nonlinear function (r = 0.89, P = 0.04; r = 0.96, P = 0.01). We conclude that total and newly released NE into interstitial fluid of the heart, determined by regional mass transport kinetic model, are specific measures of regional cardiac-specific sympathetic nervous system activity and are strongly related to measures of LV size and systolic performance. These data support the concept that this new model of organ-specific NE kinetics has physiological relevance.     

Fungal growth inside saline-filled implants and the role of injection ports in fungal translocation: in vitro study

Infection is a serious complication of breast augmentation and tissue expansion with inflatable devices. Several reports have shown that fungi may be able to survive, colonize, and even cause infection in saline-filled devices. The mechanism of how they penetrate, spread, and colonize inside the inflatable implants is not exactly understood. The authors assessed both the expander membrane and the port in terms of leakage and penetration of Candida albicans and Aspergillus niger in an in vitro model. Thirty saline-filled expanders connected to the injection port were placed in sterile containers filled with tryptic soy broth culture medium to simulate the clinical situation in phases I and II. Intact and multipunctured ports were used in the first and second phases of the study, respectively. Either the container or the implant was inoculated with one of these fungi, and six implants in containers without fungal inoculation served as controls. As a third phase, intraluminal survival of fungi was investigated in saline-filled containers (n = 12) in 21 days. The silicone membrane, with its intact connecting tube and port, was impermeable to these fungi, whereas both fungi were able to diffuse inside-out or outside-in through the punctured ports. C. albicans did not survive beyond 18 days in saline, whereas A. niger continued to multiply at day 21. Chemical analyses of the implant fluids revealed that the contents of the culture medium diffused into the implants in phases I and II. The data show that an intact silicone membrane is impermeable to fungi, and punctured ports allow translocation of fungi into the implants. Fungi can grow and reproduce in a saline-only environment, and their survival periods differ among the species. Furthermore, their survival may be enhanced by the influx of substances through the implant shell.     

Mendelian hypertension with brachydactyly as a molecular genetic lesson in regulatory physiology

Mendelian forms of hypertension have delivered a treasure trove of novel genes. To date, the molecular mechanisms of five such syndromes have been largely clarified, including glucocorticoid-remediable aldosteronism, Liddle's syndrome, apparent mineralocorticoid excess, an activating mutation of the mineralocorticoid receptor, and pseudohypoaldosteronism type 2. Each of these conditions features salt sensitivity with increased sodium and volume reabsorption by the kidney and low plasma renin activity. None of the gene loci for these syndromes has been convincingly linked to hypertension in the general population. We are investigating kindreds who have autosomal-dominant hypertension and brachydactyly. Affected persons invariably have both anomalies. The hypertension is severe and results in death at about age 50 years from stroke. The condition resembles essential hypertension, because renin, aldosterone, and norepinephrine responses are normal and no salt sensitivity is present. The response to antihypertensive drugs is general. Another feature is diminished baroreflex sensitivity with markedly impaired blood pressure buffering. Furthermore, the ventrolateral medulla may be compromised in these patients, because neurovascular anomalies are a regular finding. We mapped the gene(s) for this disease to chromosome 12p and narrowed the chromosomal region by studying more affected families. Interestingly, the same locus was recently mapped in Chinese families with essential hypertension. Our 3-centimorgan region contains genes encoding a phosphodiesterase, an ATP-dependent potassium channel, and its regulator the sulfonylurea receptor 2. Screening of the coding regions revealed that none of these candidate genes harbor obvious mutations; however, other genetic mechanisms may nevertheless compromise their function. Our study underscores the importance of regulatory physiology to the understanding of a complex genetic syndrome.     

Effects of harman and harmine on naloxone-precipitated withdrawal syndrome in morphine-dependent rats

The effects of the beta-carbolines, harman and harmine, on naloxone-precipitated withdrawal syndrome in morphine-dependent rats were investigated. Two morphine pellets containing 75 mg morphine base were implanted subcutaneously in the scapular area of adult male Wistar rats (200-250 g) under light ether anesthesia. Rats were then assigned to several groups (n = 12 for each group). Seventy-two hours after morphine implantation, harman (5 and 10 mg/kg), harmine (5 and 10 mg/kg) or saline was injected to rats intraperitoneally (ip). After 45 min, a morphine withdrawal syndrome was precipitated by naloxone (2 mg/kg, ip), and morphine withdrawal signs were observed and evaluated for 15 min. Harmine (5 and 10 mg/kg) attenuated significantly the intensity of all signs of morphine withdrawal except for jumping. While jumping behaviour appearing in morphine withdrawal was intensified by harman (5 and 10 mg/kg) treatment, harmine administration did not produce any significant change in the intensity of this sign. Harman attenuated significantly the intensity of wet dog shakes, writhing, defecation, tremor and ptosis. However, it produced no significant changes in the intensity of teeth chattering and diarrhea. Our results suggest that harman and harmine, beta-carbolines, have some beneficial effects on naloxone-precipitated morphine withdrawal syndrome in rats. Findings from the present study also indicated that harmine was more effective than harman on morphine abstinence syndrome.