Descriptive epidemiology of induced abortion in Italy 1979–1990

Trends of induced abortions in Italy from 1979 to 1990 have been analysed in terms of overall age-standardised rates and ratios, and according to various characteristics of the women. Temporal trends were characterised by an increase of rates from 11.3/1,000 women aged 15–49 in 1979 to 16.5 in 1982 and then followed by a steady decrease to 11.1/1,000 in 1990. Ratios increased from 228/1,000 livebirths in 1979 to 389 in 1984 and then declined to 286 in 1990. Thus, the overall declines from the early 1980's to 1990 were 33% in rates and 26% in ratios. The same pattern was followed by rates and ratios in various age groups. The highest rates were observed in women aged 25–29 years (27.0/1,000 in 1982 and 17.9/1,000 in 1988) and 30–34 years (25.5/1,000 in 1982 and 19.0/1,000 in 1988), and the lowest ones were in women aged 45–49 (1.0/1,000 in 1982 and 0.8/1,000 in 1988). Ratios reached the highest values in 1984 in most age groups, particularly in women between 40 and 49 years and under 20 years. Ratios increased constantly with number of previous deliveries. At all levels of education,a decline in rates has been observed since 1982, but in the highest educational level,the decline started earlier and was more substantial. The decline in rates among more educated women from 1982 to 1987 was 36%, but it was only 9% among less educated ones. Scope for further preventive action is indicated by the differences according to education and by the slowing down of the decline in the more recent years. This preventive intervention should be focused particularly to women of lower educational level and to those with two or more births.     

Tea consumption and cancer risk.

The relationship between tea consumption and cancer risk has been analyzed using data from an integrated series of case-control studies conducted in northern Italy between 1983 and 1990. The dataset included 119 histologically confirmed cancers of the oral cavity and pharynx, 294 of the esophagus, 564 of the stomach, 673 of the colon, 406 of the rectum, 258 of the liver, 41 of the gallbladder, 303 of the pancreas, 149 of the larynx, 2,860 of the breast, 567 of the endometrium, 742 of the ovary, 107 of the prostate, 365 of the bladder, 147 of the kidney, 120 of the thyroid, and a total of 6,147 controls admitted to hospital for acute nonneoplastic conditions unrelated to long-term dietary modifications. Multivariate relative risks (RR) for tea consumption were derived after allowance for age, sex, area of residence, education, smoking, and coffee consumption. All the estimates for tea consumption were close to unity, the highest values being 1.4 for rectum, gallbladder, and endometrium. There was no association with cancers of the oral cavity (RR = 0.6), esophagus (RR = 1.0), stomach (RR = 1.0), bladder (RR = 0.8), kidney (RR = 1.1), prostate (RR = 0.9), or any other site considered. Although in northern Italy tea was consumed daily by only a limited proportion of the population, this integrated series of studies offers further reassuring evidence on the relationship between tea and cancer risk.     

Willingness to receive intravenous buprenorphine treatment in opioid-dependent people refractory to oral opioid maintenance treatment: results from a community-based survey in France

Background

Injectable opioids are an interesting option for people who inject drugs (PWID) that do not respond to oral Opioid Maintenance Treatment (OMT). To date, intravenous (IV) buprenorphine - a safer drug than full-opioid agonists in terms of overdose risk - has never been tested in a clinical trial on opioid dependence. We designed a survey to better understand the profile of PWID eligible for IV buprenorphine, and their willingness to receive it.

Methods

This cross-sectional community-based national survey was conducted through face-to-face interviews (in low-threshold and addiction care services) and online questionnaires (on https://psychoactif.org and other websites). Among the 557 participants, we selected those who were eligible for IV buprenorphine treatment (history of oral OMT, regular opioid injection) (n = 371). We used regression models to study factors associated with willingness to receive IV buprenorphine treatment among those with data on willingness (n = 353). In those who were willing (n = 294), we subsequently studied their willingness to receive daily supervised IV buprenorphine treatment.

Results

Among the selected 353 participants, 59% mainly injected buprenorphine, 15% heroin, 16% morphine sulfate and 10% other opioids. Eighty-three percent of the sample reported willingness to receive IV buprenorphine treatment. Factors associated with willingness were: more than 5 injection-related complications, regular buprenorphine injection, no lifetime overdose, and completion of the questionnaire online. Factors associated with unwillingness to receive daily supervised treatment were younger age (OR[IC95%]=1.04[1.01; 1.07]) and stable housing (OR[IC95%]=0.61[0.37;1.01]) while regular heroin injectors were more willing to receive daily supervision (OR[IC95%]=2.94 [1.42; 6.10]).

Conclusions

PWID were very willing to receive intravenous buprenorphine as a treatment, especially those with multiple injection-related complications. In addition, our findings show that IV buprenorphine may be less acceptable to PWID who inject morphine sulfate. Young PWID and those with stable housing were unwilling to receive IV buprenorphine if daily supervision were required. This preliminary study provides useful information for the development of a clinical trial on IV buprenorphine treatment.

     

Lung anabolic activity in patients with chronic heart failure: Potential implications for clinical practice

ObjectiveThe proteins in the lungs are in constant flux, undergoing degradation and resynthesis. We investigated pulmonary protein and amino acid metabolism, the biochemical basis of the remodeling process, in individuals with chronic heart failure receiving or not receiving β-blocker therapy with bisoprolol (BIS).MethodsClinically stable rehabilitative patients with chronic heart failure, without metabolic diseases or liver/renal failure, and with a stable weight over the preceding 3 mo underwent right heart catheterization, and radial artery cannulation. Mixed central venous and arterial blood samples were drawn simultaneously to calculate the venous-arterial difference of amino acids (pulmonary uptake and release).ResultsTwenty-two patients on BIS therapy and eight not receiving BIS were analyzed. The two groups showed a net pulmonary protein synthesis (i.e., a positive value of phenylalanine [venous-arterial difference] × cardiac index product) and amino acid extraction, the rates of which were significantly lower in patients on BIS therapy. The two groups had pulmonary hypertension (mean pulmonary artery pressure >19 mmHg). Pulmonary vascular resistance was 57% higher in patients not receiving BIS than in those on BIS therapy (6.65 ± 2.90 versus 4.23 ± 1.49 mmHg/L · min^?1 · m^?2, P < 0.05). Pulmonary vascular resistance correlated positively with the pulmonary extraction of total essential amino acids (r = +0.4576, P = 0.01) and leucine (r = +0.5083, P = 0.004), the most important amino acid for protein synthesis.ConclusionPatients with chronic heart failure have increased rates of amino acid extraction and pulmonary protein synthesis, suggesting, at least in part, an increased rate of lung remodeling. Therapy with BIS attenuates lung metabolic abnormalities.     

Genetic variability of Echinococcus granulosus sensu stricto in Europe inferred by mitochondrial DNA sequences

The genetic diversity of Echinococcus granulosus sensu stricto (s.s.) metacestodes from four European countries was evaluated by the DNA sequence analysis of the cytochrome c oxidase subunit 1 (cox1) mitochondrial gene. Of the 312 organisms investigated, 132 were from Bulgaria, 35 from Hungary, 89 from Italy and 56 from Romania. Considerable intraspecific variation was observed in the mitochondrial cox1 sequences: 24 haplotypes were detected in the Eastern European population and seven in the Italian population. The Eastern European population parsimony network displayed a star-like features consisting of the most common haplotype EG1 (G1 genotype) and the three major haplotypes: EG2, EG3 and EG4. The EG1 was also the major haplotype in the Italian population network, though with a higher prevalence (73%) compared to the Eastern European network. The percentage of the population constituted by the G1 genotype was used as an indirect index to evaluate the genetic diversity within E. granulosus s.s. populations of Eurasia. A clinal correlation between the percentage of the G1 genotype and the geographical regions of Eurasia was observed: the G1 genotype is highly represented in the Mediterranean Basin; it decreases in Eastern Europe and South-West Asia and increases in China. This clinal correlation could reflect the spreading of livestock domestication from Southern-Western Asia during the Neolithic period, beginning around 12,000 BC.     

Synthesis and evaluation for biological activity of 3-alkyl and 3-halogenoalkyl-quinoxalin-2-ones variously substituted. Part 4

A new series of 3-isopropyl-, 3-trifluoromethyl- and 3-bromomethylquinoxaline-2-ones variously substituted on the benzo-moiety were synthesized and submitted to a preliminary in vitro evaluation for antibacterial, antifungal and anti-HIV activities. Furthermore, all compounds were also tested for cytotoxicity. Results of the screening showed that compound 10 exhibits moderate antimicrobial activity against Staphylococcus aureus (MIC = 33 microM), and that 25 and 26 showed interesting cytotoxicity versus mock-infected MT-4 cells. All the other compounds were inactive.     

Role of D1-like receptors in amphetamine-induced behavioral sensitization: a study using D1A receptor knockout mice

RATIONALE: The role played by D(1)-like receptors in amphetamine-induced behavioral sensitization has been examined using both the D(1)-like receptor antagonist, SCH 23390, and the D(1A) receptor knockout mouse (i.e. D(1A)-deficient mice). Studies using these two approaches have provided conflicting evidence about the importance of D(1)-like receptors for amphetamine-induced behavioral sensitization. OBJECTIVE: The purpose of the present study was to determine: (a) whether D(1A)-deficient mice exhibit amphetamine-induced locomotor sensitization after 3 and 17 drug abstinence days, and (b) whether SCH 23390, which binds to both D(1A) and D(1B) receptor subtypes, blocks development of amphetamine sensitization in wild-type and D(1A)-deficient mice. METHODS: In the first experiment, adult wild-type and D(1A)-deficient mice were injected with amphetamine (0, 1, 2, 4, or 8 mg/kg, IP) for 7 consecutive days. In the second experiment, wild-type and D(1A)-deficient mice were pretreated with SCH 23390 (0, 0.15, or 0.5 mg/kg, IP) 30 min prior to being injected with amphetamine (0 or 8 mg/kg, IP). After each daily amphetamine injection, mice were placed in activity chambers where distance traveled (i.e. horizontal locomotor activity) was measured for 60 min. On the test days, which occurred after 3 or 17 drug abstinence days, mice were injected with 1 mg/kg amphetamine and locomotion was measured for 120 min. RESULTS: Both wild-type and D(1A)-deficient mice exhibited amphetamine-induced locomotor sensitization. Pretreatment with 0.5 mg/kg SCH 23390 blocked the development of locomotor sensitization in wild-type mice, but did not alter the sensitized responding of D(1A)-deficient mice. CONCLUSIONS: It appears that D(1)-like receptors are necessary for the development of amphetamine sensitization in wild-type mice, while neither the D(1A) nor D(1B) receptor subtypes are necessary for the amphetamine-induced locomotor sensitization of D(1A)-deficient mice. A possible explanation for these conflicting results is that D(1A)-deficient mice may have a compensatory mechanism (not involving D(1B) receptors) that allows them to exhibit amphetamine-induced behavioral sensitization in the absence of the D(1A) receptor.     

The Inhibitory Effect of Shikonin on the Agonist-Induced Regulation of Vascular Contractility

Shikonin, a natural flavonoid found in the roots of Lithospermum erythrorhizon, has been shown to possess many biological functions. The present study was undertaken to investigate the influence of shikonin on vascular smooth muscle contractility and to determine the mechanism involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Shikonin significantly relaxed fluoride-, thromboxane A₂- or phorbol ester-induced vascular contraction suggesting as a possible anti-hypertensive on the agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, shikonin significantly inhibited fluoride-induced increases in pMYPT1 levels and phorbol ester-induced increases in pERK1/2 levels suggesting the mechanism involving the inhibition of Rho-kinase activity and the subsequent phosphorylation of MYPT1 and the inhibition of MEK activity and the subsequent phosphorylation of ERK1/2. This study provides evidence regarding the mechanism underlying the relaxation effect of shikonin on agonist-induced vascular contraction regardless of endothelial function.     

Leveraging the Pre-DFG Residue Thr-406 To Obtain High Kinase Selectivity in an Aminopyrazole-Type PAK1 Inhibitor Series

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Rebound contraction by nitric oxide in the longitudinal muscle of porcine gastric fundus

The rebound contraction induced by electrical field stimulation (EFS) and nitric oxide (NO) donor, S-nitroso-L-cysteine (cysNO), were investigated in the longitudinal muscle of porcine gastric fundus (LM-PGF). Under the presence of atropine and guanethidine, cysNO and EFS produced sequential relaxation-contraction in LM-PGF. Tetrodotoxin abolished the EFS-induced response, while leaving the cysNO-induced one unaffected. A soluble guanylate cyclase inhibitor, 1H-[1,2,4]-oxadiazolo-[4,3-a]-quinoxalin-1-one, inhibited both cysNO and EFS-induced biphasic response. A cGMP analogue only relaxed LM-PGF. A phosphodiesterase V inhibitor, zaprinast, prolonged the cysNO and the EFS-induced relaxation and inhibited the rebound contraction. The rebound contraction was inhibited by verapamil, an L-type Ca2+ channel blocker. The cysNO and the EFS-induced biphasic response were inhibited by ryanodine plus cyclopiazonic acid or by ruthenium red, a ryanodine-receptor blocker. LM-PGF was relaxed on exposure to caffeine and then produced a verapamil-sensitive rebound contraction during the washout period. CysNO and EFS did not induce the rebound contraction in the presence of caffeine. These results suggest that the NO-induced rebound contraction involves both Ca2+-release from the ryanodine-sensitive store and Ca2+-influx through L-type channels. Although the NO-induced biphasic response is dependent on cGMP, rapid removal of cGMP seems necessary for the rebound contraction.