Advertisement of electronic cigarettes in Italy: characteristics of online videos and the most popular promotional messages.

Given the increasing popularity of electronic cigarettes (ECs) and a lack of regulation of EC advertising, this study aimed to analyse online videos promoting ECs to assess the main marketing messages that could influence consumers' perceptions of associated risks and benefits. A web search of EC advertising videos was performed on YouTube by using keywords related to EC promotion. An evaluation grid was used to analyse promotional messages contained in each video. The most frequent promotional messages were related to health benefits (67.7%) and to the possibility of quitting smoking (57.4%). Messages that could also be appealing to adolescents and young adults, such as those promoting the multiple flavors available and the technological improvement of ECs, were present in 41.2% and 42.7% of the videos respectively. ECs similar to traditional cigarettes in appearance were included in 52.9% of the videos. EC promotional videos address messages not only to smokers who want to quit or decrease tobacco consumption but also to nonsmokers, especially young people. The use of ECs similar to traditional cigarettes may be a gateway to tobacco cigarette use. Since EC use may represent an important public health concern, regulatory policies on EC advertising should be established.

The long-term effects of bibliotherapy in depression treatment: Systematic review of randomized clinical trials.

OBJECTIVE: Literature shows bibliotherapy can be helpful for moderate depression treatment. The aim of this systematic review is to verify the long-term effects of bibliotherapy. METHODS: After bibliographic research, we included RCTs articles about bibliotherapy programme treatment of depression published in English language between 1990 and July 2017. All RCTs were assessed with Cochrane's Risk of Bias tool. RESULTS: Ten articles (reporting 8 studies involving 1347 subjects) out of 306 retrieved results were included. All studies analyze the effects of bibliotherapy after follow-up periods ranging from 3months to 3years and show quiet good quality in methods and analyses. The treatment was compared to standard treatments or no intervention in all studies. After long-term period follow-ups, six studies, including adults, reported a decrease of depressive symptoms, while four studies including young people did not show significant results. CONCLUSION: Bibliotherapy appears to be effective in the reduction of adults depressive symptoms in the long-term period, providing an affordable prompt treatment that could reduce further medications. The results of the present review suggest that bibliotherapy could play an important role in the treatment of a serious mental health issue. Further studies should be conducted to strengthen the evidence of bibliotherapy's efficacy.

A Pilot Study of Femoropopliteal Artery Revascularisation with a Low Dose Paclitaxel Coated Balloon: Is Predilatation Necessary?

OBJECTIVE/BACKGROUND: The objective was to compare 2 year outcomes in patients treated with or without predilatation prior to drug coated balloon (DCB) angioplasty for symptomatic femoropopliteal lesions. METHODS: This prospective multicentre pilot study was conducted at three sites in Germany. It compared claudicants undergoing predilatation with a bare percutaneous transluminal angioplasty (PTA) balloon before DCB (predilatation group) with patients undergoing direct DCB (direct DCB group). Patients were followed for 2 years. Outcomes included late lumen loss at 6 months, and ankle brachial index (ABI), major adverse events, and primary patency at 2 years. A Clinical Events Committee and core laboratories analysed adverse events and angiographic/duplex images, respectively. RESULTS: Between December 2011 and November 2012, 50 patients were enrolled to the predilatation group (12% total occlusions) and 28 to the direct DCB group (5% total occlusions). Follow-up compliance at the 2 year visit was 88% (n = 44) and 86% (n = 24), respectively. Late lumen loss at 6 months was lower in the direct DCB group (0.03 ± 0.68 mm vs. 0.54 ± 0.97 mm; p = .01). Major adverse events over 2 years occurred in seven (15%) patients who underwent predilatation and in five (19%) after direct DCB. Mean ABI at 2 years was 0.94 ± 0.15 after predilatation and 1.0 ± 0.12 after direct DCB. Over 2 years, primary patency (80.3% vs. 78.2%; p = .55) was not statistically different between the groups. After propensity score adjustments, 2 year findings remained unchanged. CONCLUSION: Paclitaxel coated PTA, with or without bare predilatation, is effective over 2 years in symptomatic patients with femoropopliteal stenotic lesions. Adequately powered randomised controlled comparisons are required to confirm these preliminary results.

High-normal blood pressure and impaired renal function. A prospective study in a population-based cohort.

AIM: The association between high-normal blood pressure and the impairment of renal function is highly controversial. We analysed the contribution of high-normal blood pressure on incident impaired renal function. METHODS: The study was performed in a population-based cohort of 1307 subjects free of diabetes, cardiovascular and renal disease at baseline, who attended both at baseline and after 6-year follow-up a metabolic screening. The outcome was incident impaired renal function, defined as a glomerular filtration rate <60 mL/min/1.73 m2. RESULTS: Incidence of impaired renal function was 2.5%, 4.5%, 8.7% and 10.8% in optimal, normal, high-normal blood pressure and hypertension, respectively. Adjusted relative odds ratio (OR) of impaired renal function were modelled using logistic regression analyses including multiple confounders. The adjusted OR were 1.6 (95% CI 0.5-5.0) for normal blood pressure, 3.4 (1.2-10.3) for high-normal blood pressure and 3.7 (1.3-10.7) for hypertension. Results were similar after excluding overweight or obese patients. CONCLUSION: High-normal blood pressure is an independent predictor of impaired renal function. Trials are warranted to test if therapeutic intervention on blood pressure is justified also in subjects with high-normal blood pressure to preserve renal function.

Zebrafish keratin 8 is expressed at high levels in the epidermis of regenerating caudal fin.

Cytokeratins are structural proteins of the intermediate filament family and are mainly expressed in epithelial cells. In several vertebrates it has been shown that keratin 8 is expressed in simple epithelial tissues, some non-epithelial tissue and in hyper-proliferative tissues during development and tumor transformation. We previously cloned and characterised the zebrafish (Danio rerio) homologous cytokeratin 8 cDNA (zfk8) which was described as an epidermal marker during zebrafish development. It has been found that the zfk8 gene is normally expressed in simple epithelia in embryonic and mature zebrafish. Using whole-mount in situ hybridisation, we show in this report that expression of zfk8 is tightly linked to the regeneration of caudal fin and exclusively observed in epidermal cells. It is strongly expressed in the epidermis overlaying the inter-rays zone of regenerating caudal fin. Our results indicate that in zebrafish, cytokeratin 8 is a suitable epidermal marker during regeneration.

A seven year anthropobiological survey on the distribution of abnormal hemoglobins in Cameroon.

Within the frame of an anthropobiological survey on some populations of Cameroon (1985-1991), Hb beta data were collected from numerous ethnic groups including Bakaka, Bamileke, Daba, Fali, Guiziga, Kanuri, Mada, Mafa, Mundang, Uldeme, Podokwo, Tali, Tupuri, Fulbe, Mandara, Ewondo and Bassa. Hb beta *S allele frequencies ranged from 0.008 +/- 0.003 (among Fali) to 0.152 +/- 0.020 (among Mandara) and 0.152 +/- 0.044 (among Podokwo), whereas Hb beta *S was found to be absent among Tupuri. Hb beta *C was observed among Bamileke (0.001 +/- 0.001), Fali (0.003 +/- 0.002), Fulbe (0.002 +/- 0.002), Mafa (0.005 +/- 0.005), Mundang (0.005 +/- 0.005), Tupuri (0.010 +/- 0.007) and Podokwo (0.015 +/- 0.015). The possible reasons for these variations in allele frequencies are discussed.

Pharmacological and biochemical effects of the cardiotonic agent Org10325 in isolated cardiac and vascular tissue preparations.

1. The pharmacological and biochemical effects of a novel cardiotonic agent, Org10325 have been studied in isolated cardiac and vascular tissue preparations. 2. Org10325 produced concentration-dependent (0.15-4.8 mM) positive inotropic, positive chronotropic and vascular relaxant responses in rabbit isolated papillary, atrial and aortic preparations, respectively. The maximal chronotropic effect (45%) was significantly less than the isoprenaline maximum. The inotropic effects of Org10325 were not modified by alpha- or beta-adrenoceptor blockade or by pretreatment with reserpine. Org10325 was at least 23 times more potent at relaxing aortic strips pre-contracted with phenylephrine than with KCl. 3. Org10325 (74 microM) potentiated (10-14 fold) the positive inotropic effects of isoprenaline in rabbit isolated papillary muscles. Carbachol inhibited the positive inotropic effect of Org10325. Both the positive inotropic and vasorelaxant effects of Org10325 were accompanied by increases in cyclic AMP but not cyclic GMP. 4. In rat perfused heart preparation Org10325 increased phosphorylase a, cyclic AMP-dependent protein kinase activities and stimulated phosphorylation of contractile proteins (troponin-I and C-protein). 5. Org10325 selectively inhibited the cyclic AMP hydrolytic activity of cyclic AMP high affinity cyclic nucleotide phosphodiesterase (PDE) isoenzymes, PDE III (IC50 65 microM) and PDE IV (IC50 71 microM), from rabbit cardiac ventricle. Weak inhibition (IC50 greater than 250 microM) of PDE I and PDE II was observed. 6. The results show that the cardiac and vascular effects of Org10325 are mediated by an increase in cellular cyclic AMP due to inhibition of PDE III and PDE IV activities. However, in contrast to other PDE-inhibitors OrglO325 produced a marked increase in relaxation time of isolated papillary muscle suggesting the involvement of additional cyclic AMP-independent mechanisms of action.

Evaluation of the sensitivity of microfilter paper assays in an anthropological study: results of samples from Cameroon and Tanzania.

Microfilter absorbed whole blood samples from 223 Tanzanian babies and 189 adults from Cameroon have been examined. Blood specimens are difficult to obtain from African suburban and rural areas, and lack of storage and transportation facilities can prevent the collection of samples. We evaluated some microassays employing whole blood collected on filter paper. This method is a well established technique in neonatal screening for endocrinometabolic diseases. We also developed microassays for whole dried blood spots to type AB0 blood groups and HIV disease using commercial reagents. Phenotype and gene frequencies for AB0 and hemoglobin systems as well as our results concerning the typings of thyroxine (T4), thyroid stimulating hormone (TSH), human immunodeficiency virus (HIV) and hepatitis B virus (HBV) are reported.

Electrophysiologic effects of Org 7797, a new steroidal antiarrhythmic agent: comparison with class 1a, 1b, and 1c drugs.

The in vitro electrophysiologic effects of a new class I steroidal antiarrhythmic agent, Org 7797 (2-10 microM) were evaluated in porcine ventricular and Purkinje tissue using conventional microelectrode techniques. Org 7797-induced decreases in Vmax were both frequency- and voltage-dependent. Both the rate of onset and the time course of decay of sodium channel block were slow and similar to those obtained with the 1c drug propafenone. The kinetics of block by lignocaine (1b) were fast whereas those of disopyramide (1a) were intermediate. Rate constants (determined at 1.0 Hz) were 0.187, 0.078, and 0.074 for disopyramide, propafenone, and Org 7797, respectively, in concentrations giving approximately equivalent decreases in Vmax. Onset block with lignocaine was too fast to measure. The effective refractory period (ERP) was prolonged to a greater extent by lignocaine and disopyramide than by propafenone or Org 7797, but the increase in ERP in response to disopyramide resulted largely from prolongation of action potential duration (APD). The effects of Org 7797 on ERP relative to APD were more similar to those of propafenone. We conclude that Org 7797 is a class 1c agent.

Bovine hemoglobin as a basis for artificial oxygen carriers.

Under physiological conditions of pH and [Cl-] ions the oxygen affinity of bovine hemoglobin is lower than that of human hemoglobin. The difference tends to disappear at low ionic strength, while it increases at high ionic strength. In the presence of Cl- ions bovine hemoglobin is not sensitive to 2,3-DPG, while in the absence of Cl- ions human and bovine hemoglobin respond to 2,3-DPG in a similar way. This is due to a high preferential binding of halogens by the deoxy-conformation in the bovine system. Reaction of deoxy-bovine hemoglobin with 2,3-dibromo-salycyl-fumarate results in a decreased oxygen affinity. Compounds can be purified by anion exchange chromatography which have the sedimentation velocity of tetrameric hemoglobins. They fail to dissociate into dimers at acid pH because of the presence of intramolecular crosslinks. Reverse phase chromatography shows that both kind of subunits are modified by the reaction. The half time of retention in rats of these tetramers is near 5 h. Bovine red cells do not contain 2,3-DPG, therefore they can be stored in the cold in saline for at least 2 months without significant modifications of their oxygen affinity. The oxygen affinity of bovine red cells can be modulated by addition and subtraction of Cl- ions from and by changing the pH of the media.

Comparative antiarrhythmic and electrophysiological effects of drugs known to inhibit calmodulin (TFP, W7 and bepridil).

The potential antiarrhythmic and electrophysiological actions of drugs known to inhibit calmodulin, i.e. trifluoperazine (TFP) and N-(6-aminohexyl)-5-chloro-1-naphthalene sulphonamide (W7) have been compared with bepridil, whose antiarrhythmic actions have previously been ascribed to blockade of the fast inward sodium current in cardiac tissue. Like bepridil, both TFP and W7 reduced the severity of arrhythmias evoked by 30 min of coronary artery occlusion in the anaesthetized rat. TFP (2.5-10 mg kg-1, i.v.), W7 (2.5-10 mg kg-1, i.v.) and bepridil (1-5 mg kg-1, i.v.) also antagonized the development of ventricular fibrillation induced by 5 min of occlusion followed by reperfusion. All three drugs also reduced mortality. TFP and bepridil also reduced the incidence of reperfusion-induced ventricular tachycardia whilst all 3 drugs reduced its duration. Although TFP was shown to possess alpha-adrenoceptor blocking properties, the classical alpha-blocker, phentolamine, failed to reduce significantly the incidence or severity of reperfusion arrhythmias. In contrast to bepridil (2-20 microM), which markedly reduced the maximum rate of depolarization (Vmax) of guinea-pig isolated papillary muscle, W7(5-50 microM) showed only weak effects on Vmax and was at least 10 times less potent than bepridil whilst TFP only reduced Vmax in high concentrations (40-100 microM) which lowered resting membrane potential. Unlike bepridil, neither TFP (4-40 microM) nor W7 prolonged the absolute refractory period. The results suggest that drugs which inhibit calmodulin confer protection against both ischaemia-and reperfusion-induced arrhythmias in the rat. Although the electrophysiological actions of bepridil would adequately account for its antiarrhythmic activity, the same cannot be said of W7 and especially TFP. In conclusion, calmodulin antagonism may constitute a mechanism of antiarrhythmic activity.

The effects of bepridil compared with calcium antagonists on rat and rabbit aorta.

The vasodilator (relaxant) action of the antianginal agent bepridil was compared with that of drugs known to either block membrane calcium channels, to be calmodulin antagonists or to inhibit intracellular calcium flux using rat and rabbit aortic strips. IC50 values were obtained for relaxation of tonic contractions induced by either potassium (K+) or phenylephrine (PE). The order of relaxant specificity against K+ compared with PE in both rabbit and rat tissue preparations was nisoldipine = nifedipine greater than diltiazem greater than verapamil greater than bepridil greater than PrMDI greater than W7 greater than TFP greater than phentolamine. The ratio for flunarizine equalled that of bepridil in rabbit and that of verapamil in rat. The calmodulin antagonist TFP showed additional alpha-adrenoceptor blocking properties. Analysis of concentration response curves to the antagonists together with PE/K+ ratios revealed a different profile for each drug tested on rabbit aorta. The range of PE/K+ ratios was much wider in rabbit compared to rat. The results suggest that, with the method used, rabbit aortic strips offer a simple technique for drug profiling and allows a clearer differentiation between membrane active and intracellularly acting drugs than does rat aorta. The profile of bepridil resembled more that of intracellularly acting drugs suggesting that intracellular actions (possibly calmodulin inhibition) may play a substantial role in its dilator actions on vascular smooth muscle.

The effect of somatostatin on the release of thyrotropin and its subunits from bovine anterior pituitary cells in vitro.

The effects of somatostatin (SRIF) on the production and release of TSH and its subunits have been investigated in bovine anterior pituitary monolayer cultures. SRIF caused a dose-dependent inhibition of TSH and subunit release by TRH, with a half-maximal effective dose of 3 X 10(-8) M. This effect was time dependent and was greater for TSH than for its subunits. However, the basal release and total production of TSH and its subunits over a 24-h period were not affected by SRIF. The effect of SRIF was additive to that of thyroid hormones in suppressing the release of TSH and its subunits by TRH. A combination of SRIF and thyroid hormone completely suppressed the release of TSH and its subunits by TRH. In contrast, thyroid hormones caused a dose-dependent inhibition of the total production, as well as the release, of TSH and its subunits induced by TRH. Furthermore, thyroid hormones produced a dose-dependent increase (r = 0.81; P less than 0.001) in the effectiveness of a single dose of SRIF in suppressing TSH release by TRH. Analysis of these data revealed that thyroid hormones interacted synergistically with the SRIF effect to suppress TRH-mediated TSH and subunit release.

Pure alpha-secreting pituitary adenomas.

Isolated hypersecretion of the alpha subunit of the glycoprotein hormones occurred in two men with previously diagnosed "nonfunctioning chromophobe adenomas." The alpha hypersecretion was unresponsive to hypothalamic releasing hormone, thyroid hormone, and sex-steroid hormones. After trans-sphenoidal surgery and conventional pituitary irradiation, alpha secretion was decreased. Increased quantities of immunologically active and biologically inactive luteinizing hormone (LH) material were detected in serum and in tumor homogenate. Immunologic and gel-chromatographic studies determined that only the alpha subunit was present and that it was cross-reacting in the LH immunoassay. These studies suggest that the alpha subunit may be a useful marker of pituitary tumors, particularly in patients without clinical evidence of hormonal hypersecretion.

Production and release of thyrotropin and its subunits by monolayer cultures containing bovine anterior pituitary cells.

We have developed a dispersed cell monolayer system derived from bovine anterior pituitary glands. Fresh 1- to 6-week-old calf anterior pituitaries were mechanically and enzymatically dispersed and incubated with Dulbecco's Modified Minimal Essential Medium containing 10% hypothyroid goat serum. The media and cell extracts from confluent monolayers were analyzed for bovine TSH and free alpha, and TSH beta subunits by specific homologous RIAs. Basal levels of TSH, free alpha, and free TSH beta subunits in the media were 6.2 +/- 0.3, and 0.95 +/- 0.05 ng/10(6) cells . 24 h, respectively. Hence, an 8- to 10-fold excess of free alpha over free TSH beta subunits was released into the medium. Intracellular basal levels of TSH, free alpha, and free TSH beta subunits were 27.6 +/- 1.7, 10.7 +/- 0.2, and 2.6 +/- 0.3 ng/10(6) cells . 24 h, respectively, and indicated a 3- to 4-fold excess of free alpha over free TSH beta subunits within the cells. The total alpha-subunit to total beta-subunit ratio was 2:1. TRH stimulated release of TSH and its subunits in a dose-dependent fashion, with a half-maximal dose of 2 nM and a maximal response dose of 10 nM. Stimulation with 100 nM TRH increased the levels of TSH, free alpha, and free TSH beta subunits (450-900%, 180-200%, and 300-400%, respectively) in medium, with concomitant decreases within cells. Treatment with thyroid hormones decreased basal and blunted TRH-stimulated levels of TSH and its subunits in medium but had no effect on intracellular stores. However, large doses of T4 (25 nM) or T3 (1 nM) did not completely abolish the TRH (100 nM)-stimulated hormone response. TRH and thyroid hormones affect the release of TSH and TSH beta to a greater extent than they do the alpha-subunit. Finally, total alpha and TSH beta subunit production was increased with TRH stimulation and decreased with thyroid hormone exposure. Thus, an in vitro system to study the net production and secretion of TSH and its subunits in the normal pituitary thyrotrope has been established. (Endocrinology 108: 387, 1981)

Alpha subunit contamination of human albumin preparations: interference in radioimmunoassy.

Certain preparations of human serum albumin have been found to decrease the apparent titer of antisera to alpha subunit of human TSH (hTSH-alpha) and the sensitivity of the resultant radioimmunoassay for the immunologically common alpha subunit of the human glycoprotein hormones. Utilizing bovine serum albumin as the carrier protein, antisera to hTSH-alpha had 20-fold higher titers, and the resultant radioimmunoassay demonstrated 20-fold greater sensitivity for alpha subunit. Interference in the alpha immunoassay was not caused by protease since protease inhibitors did not eliminate it. Gel chromatography of human serum albumin revealed alph immunoactivity in an elution position identical to that of standard alpha subunit. Only certain human serum albumin preparations demonstrated interference in the radioimmunoassay because of the species specificity of the alpha subunit.A possible explanation for the alpha subunit contamination of human albumin preparations may be contamination of the serum source with placental blood, which contains large quantities of the alpha subunit of human chorionic gonadotropin.