Non-dioxin-like organic toxicant PCB153 modulates sphingolipid metabolism in liver progenitor cells: its role in Cx43-formed gap junction impairment.

The non-dioxin-like environmental toxicant 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153), member of a group of persistent organic pollutants wide-spread throughout the environment, reduces gap junction intercellular communication (GJIC), an event possibly associated with tumor promotion. Since very few studies have investigated the signaling effectors and mode(s) of action of PCB153, and it is known that the gap junction (GJ) protein Cx43 can be regulated by the bioactive sphingolipid (SL) sphingosine 1-phosphate (S1P), this in vitro study mainly addresses whether SL metabolism is affected by PCB153 in rat liver epithelial WB-F344 cells. PCB153 treatment obtained significant changes in the S1P/ceramide (Cer) ratio, known to be crucial in determining cell fate. In particular, an increase in S1P at 30 min and a decrease of the bioactive lipid at 3 h were observed, whereas Cer level increased at 1 h and 24 h. Notably, a time-dependent modulation of sphingosine kinase (SphK), the enzyme responsible for S1P synthesis, and of its regulators, ERK1/2 and protein phosphatase PP2A, supports the involvement of these signaling effectors in PCB153 toxicity. Electrophysiological analyses, furthermore, indicated that the lipophilic environmental toxicant significantly reduced GJ biophysical properties, affecting both voltage-dependent (such as those formed by Cx43 and/or Cx32) and voltage-independent channels, thereby demonstrating that PCB153 may act differently on GJs formed by distinct Cx isoforms. SphK down-regulation alone induced GJIC impairment, and, when combined with PCB153, the acute effect on GJ suppression was additive. Moreover, after enzyme-specific gene silencing, the SphK1 isoform appears to be responsible for down-regulating Cx43 expression, while being the target of PCB153 at short-term exposure. In conclusion, we provide the first evidence of novel effectors in PCB153 toxic action in rat liver stem-like cells, leading us to consider SLs as potential markers for preventing GJIC deregulation and, thus, the tumorigenic action elicited by this environmental toxicant.

HA222 polymorphism in Influenza A(H1N1) 2009 isolates from Intensive Care Units and ambulatory patients during three influenza seasons.

Amino acid substitutions which can affect the receptor binding specificity of the influenza virus, like the substitution of aspartic acid with glycine in position 222 of the haemagglutinin (HA) of influenza virus A(H1N1) 2009, have been associated with increased viral pathogenicity and increased tropism for the lower respiratory tract. In this paper, the polymorphic site 222 and the site 223 of the HA1 polypeptide of H1N1 2009 viruses were analyzed in order to better clarify the role of these substitutions in H1N1 2009 virus virulence. Viral strains included in this study were collected in Tuscany during 3 different influenza seasons from patients with severe as well as with mild forms of influenza caused by A(H1N1) 2009 virus. In addition, the oseltamivir resistance of the H1N1 2009 strains circulating during the same seasons was monitored with the aim to evaluate whether these changes in the HA and in neuraminidase (NA) tend to be linked and to influence each other. Altogether, the results indicate that in severe forms of influenza viral population is more variable than in mild influenza, as regards the site 222. The frequency of such substitutions varied among the three seasons, it was highest in the season 2010-2011 and very low in the season 2012-2013. However these differences were not significant.

Investigation of an imported case of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection in Florence, Italy, May to June 2013.

On 31 May 2013, the first case of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection in Italy was laboratory confirmed in a previously healthy adult man, who developed pneumonia with moderate respiratory distress after returning from a holiday in Jordan. Two secondary cases were identified through contact tracing, among family members and colleagues who had not previously travelled abroad. Both secondary cases developed mild illness. All three patients recovered fully.

Contrast-enhanced ultrasonography of peripheral soft-tissue tumors: Feasibility study and preliminary results.

OBJECTIVES: To determine the diagnostic value of contrast-enhanced ultrasonography, to differentiate benign and malignant soft-tissue tumors and to assess the feasibility and interest of modelling enhancement curves. PATIENTS AND METHODS: This retrospective study includes 118 patients with soft-tissue tumors, examined with ultrasound after injection of SonoVue(®), a contrast product. The raw data were treated with CHI-Q acquisition software to model the enhancement curves. We analyzed tumor uptake of the contrast product visually and studied the enhancement curves, characterized by five parameters: peak intensity, time to peak, mean transit time, initial slope, and area under the curve. RESULTS: There were 81 benign and 37 malignant tumors. For a diagnosis of benign tumor, the absence of contrast uptake had a sensitivity of 60%, a specificity of 68%, a positive predictive value of 50% and a negative predictive of 83%. Study of the 70 curves obtained (48 benign and 22 malignant tumors) showed that the parameters of area under the curve (Chi(2)=8.6 and P<0.005), slope (Chi(2)=8.12 and P=0.004), and peak intensity (Chi(2)=7.55, P=0.005) differed significantly between the two populations. CONCLUSION: Absence of contrast uptake suggests a benign lesion. The study of enhancement curves showed significant differences between the different tumor populations.

Proliferative activity and motoneurone recruitment persist at the spinal cord central canal during larval and some postlarval stages in the rainbow trout (Oncorhynchus mykiss).

We previously found a linear relationship between the cross sectional myotomal area and the motoneurone number in the growing trout during postlarval stages. These neurones increased in number until a fish length of 150 mm, which prompted us to examine how motor neurones are recruited afterwards to meet the growth of their target myotomal muscle. Young adult (260 mm in length), fingerlings (F, 120-170 mm), fry (Fr, 70 mm) and eleutherembryos (Es, 20-30 mm) of rainbow trout (Oncorhyncus mykiss) were employed in this study. PCNA immunohistochemistry was used for monitoring the proliferative activity in the epithelium of the spinal cord central canal. This activity was quantified as the number of PCNA labelled cells for each spinal cord section. In Es and Fry, a mean value of 3-5 labelled cells for each section was found with a sharp decrease in young F (120 mm long). After this fish length, it was not possible to quantitatively evaluate the proliferative activity at the central canal. However, labelled cells were seldom found in the spinal cord sections until a fish length of 260 mm. From these data it is possible to conclude that motoneurone recruitment in the trout spinal cord is down-regulated at the F stage. Afterwards, we found that motoneurones increase in size to meet the growth of their target myotomal muscle.

Estradiol enhances the resistance of LDL to oxidation by stabilizing apoB-100 conformation.

Among different proposed mechanisms to account for the protection exerted by estrogens against cardiovascular diseases, the antioxidant effect has attracted considerable attention. We confirmed that 17-beta-estradiol (E2), when added to human LDL at a 6:1 ratio to apoB-100, markedly delays the phase of massive LDL lipid peroxidation induced by Cu(2+). We also observed an increased oxidative resistance of E2-treated LDL by monitoring the early phase of oxidative degradation on the basis of increased LDL surface polarity by the generalized polarization of the lipophilic fluorescent probe 2-(dimethylamino)-6-lauroylnaphthalene (Laurdan). A scavenging of free radicals by E2 is ruled out since, consistent with its structure, its rate constant for the reduction of peroxy radicals is extremely low, i.e., 0.02% of that of vitamin E. Tryptophan fluorescence lifetime and circular dichroism measurements revealed that (i) apoB-100 undergoes a conformational modification and a progressive loss of secondary structure during lipid peroxidation; (ii) E2 increases apoB-100 secondary structure and modifies its conformation; and (iii) the apoB-100 conformational change induced by E2 makes this protein resistant to modifications brought about by lipid peroxidation. We propose that E2, by affecting apoB-100 secondary structure and conformation, modifies the interaction of this protein with the outer layer of the LDL particle thus increasing its overall oxidative resistance.

[The value of sialo-MRI in the study of salivary gland duct pathology]. / Intérêt de la sialo-IRM dans l'exploration des pathologies canalaires des glandes salivaires.

Usual imaging diagnostic for salivary glands is sialography. Sialography is not stripped of disadvantages and failures. The MRI-sialography is an examination which is carried out without any injection of contrast's product (without catheterization or intravenous injection). It is thus noninvasive and painless. The complete study of salivary gland and its ducts is always possible and could not be blocked by local or loco-regional conditions. It allows exploration of several salivary glands in the same time. We think that the MRI-sialography must find its place in the diagnosis arsenal for salivary pathology in spite of its current handicaps represented by its cost and the difficulty of access to the apparatuses.

Differences in erythrocyte membrane cholesterol to phospholipids ratio in postmenopausal women with and without hormone replacement.

OBJECTIVES: To investigate the changes in the cholesterol:phospholipids (C/PL) ratio of erythrocyte membrane in post-menopausal women with and without hormone replacement therapy (HRT). STUDY DESIGN: A cross-sectional study including 83 patients divided into three groups according to HRT (group 1, no HRT (n = 52); group 2, combined HRT (n = 16); and group 3, estrogen-only therapy (n = 15)). RESULTS: The C/PL ratio was lower in group 2 with respect to group 1 and group 3 (P = 0.03). No difference was found in erythrocyte membrane cholesterol between the three groups; however, the phospholipid concentration was higher in group 2 with respect to the other groups (P < 0.05). In the control group, C/PL values correlated positively with plasma LDL levels (P < 0.005) and negatively with HDL levels (P < 0.005). CONCLUSIONS: From our data the addition of progestogens in HRT appears to decrease the C/PL of the erythrocyte membrane possibly resulting in a beneficial effect on rheological properties of erythrocyte membrane. The results of our study thus suggest additional benefits from supplementation of progestogens in HRT, in addition to prevention of estrogen dependent endometrial hyperplasia and adenocarcinoma.

[Branchial cyst of unusual localization: report of a case and considerations on organogenesis]. / Kyste branchial de localisation inhabituelle: rapport d'un cas et considérations sur l'organogénèse.

We report a case of branchial cyst of unusual location. A asymptomatic 41-year-old man had a nontender deeply located left neck mass. Sonography, CT scan, and MRI showed a cystic lesion posterior to the sternocleidomastoid muscle. The diagnosis of branchial cyst much debated because of this atypical location was confirmed by histologic analysis after surgical resection. During organogenesis, the important caudal proliferation of the second branchial arch generates a transient cavity, the cervical sinus, which finally becomes obliterated. The incomplete obliteration of which can result in a sinus, fistula or cyst. Such cysts typically lie at the level of the mandibular angle, anterior to the sternocleidomastoid muscle. This location has been regarded as a major diagnosis criteria, but it is not absolute. The sternocleidomastoid muscle develops apart from the branchial apparatus, caudally and anteriorly. As a result the cysts which are located on an inferior portion of the cervical sinus can lie posterior to this muscle.

The cholesterol to phospholipids ratio (C/PL) of the erythrocyte membrane in normotensive, hypertensive pregnant and in cord blood as assessed by a simple enzymatic method.

The study described was conducted to evaluate a simple enzymatic method for the study of the cholesterol/phospholipids ratio in erythrocyte membrane (C/PL) in a group of normal pregnant, of hypertensive pregnant, in non-pregnant controls and in cord blood. Subjects consisted of 28 normotensive pregnant women (NT), 14 women with pregnancy induced hypertension (PIH), 10 non-pregnant normotensive women (Non-Preg) and 14 samples obtained from umbilical cord (C) at delivery from normotensive pregnant. Red blood cells were isolated from heparinated blood samples. Lipids were extracted from erythrocytes by isopropanol/chloroform, without preparation of cell ghosts. Cholesterol content was evaluated by cholesterol oxidase and phospholipids were estimated as organic phosphorus in the total lipid extract. We found a significant difference of C/PL between the PIH group and the NT group (1.01, SD 0.11 vs. 0.76, SD 0.10, 95% CI 0.74-0.78; p < 0.001) and the Non-Preg group (0.83, SD 0.11, 95% CI 0.80-0.86; p < 0.001). Cord blood C/PL was significantly elevated with respect to NT (1.25, SD 0.13 vs. 0.76, SD 0.10; p < 0.001). The method was proven to be fast, reliable and of value for the study of the pathophysiology of the alteration of the lipid composition, i.e., the increased cholesterol content, of the red cell membrane found in hypertensive pregnant patients.

Complications in the surgical treatment of carcinoma of the endometrium.

The authors report their experience in medical and surgical complications after surgical treatment of endometrial carcinoma, from January 1976 to December 1992, 301 cases of adenocarcinoma were operated by abdominal or vaginal route. From 1980 onwards abdominal route was the most frequent (radical hysterectomy with bilateral adnexectomy Rutledge type II-III with pelvic and/or aortic lymphadenectomy). No lesion occurred either during surgery or later, in the urinary or intestinal apparatus or to the great abdomino-pelvic vessels. The only medical complication observed was one episode of cerebral ictus three days after operation. Two cases of adynamic ileus and five of ventral hernia occurred.

[Hemangiopericytoma. Apropos of a case in the thoracic muscles. Contribution of imaging technics (excluding MRI). Review of the literature]. / L'hémangiopéricytome. A propos d'un cas, musculaire, thoracique. Apport de l'imagerie (IRM exclue). Revue de la littérature.

The authors describe a recurrent case of an hemangiopericytoma of the left serratus anterior muscle, touching a 21 year-old woman. The different ways of imaging are exposed and compared with data of literature. It seems that none of them offers any decisive possibility of nature diagnosis. Conversely, radiological examinations are of greatest interest in the initial lesional statement, in the follow up and in early discovery of a possible recurrence, principally in case of difficulties in the pathological examination. CT appears to have the first role among the different ways of medical imaging, initially and in the appreciation of clinical course.

[Cysts of the 2d branchial cleft. CAT scan aspects]. / Les kystes de la deuxième fente branchiale. Aspects scanographiques.

The authors describe C.T. appearances of the second branchial cleft cysts. After embryological review, they report three demonstrative observations and present the usual C.T. findings: latero cervical tumors, anterior to the sterno-cleidomastoid muscle, posterior to the submandibular gland, external to the jugulo carotidian vessels, of cystical aspect. Only the capsule is enhanced by contrast medium. C.T. brings useful informations for differential diagnosis with other cystical masses of the neck.

[Role of computed tomography in the radiologic exploration of the pterygomaxillary fossa]. / L'apport de la scanographie dans l'exploration radiologique de la fosse ptérygo-maxillaire.

The authors show the interest of C.T. examination of pterygo-maxillary region, principally in the pre-therapeutic staging of the maxillo-facial neoplasy. The anatomical division of the fossa in four regions (pterygoïd muscle area, lateropharyngeal area, pterygo-palatine fossa and retro-maxillary-malar area) can be easily applied to C.T. study. Cuts must be taken axially, in the orbito-meatal plane, and coronally always if possible, before and after administration of contrast medium. Six, out of thirty six cases studied were demonstrative. It appears that C.T. examination must be performed immediately after conventional radiology in the staging of maxillo-facial neoplasy. It shows with considerable accuracy not only the bony involvement, but also the extension in the soft tissues (interest of the densitometric study of fat) and aeric structures. It sometimes brings the solution of special clinical problems (Trismus, neuralgia of the facial nerve).

[Spasm of the renal and digestive arteries. Radiologic aspect]. / Le spasme au niveau des artères rénales et digestives. Aspect radiologique.

Spasms of the mesenteric and renal arteries are of great concern to the radiologist specialized in angiography. In most cases, they appear to be of iatrogenic origin, due to difficulties in selective catheterization and especially in superselective catheterization of the mesenteric and renal arteries. In this case, spasm may be a most unwelcome side-effect. In other less frequent cases, spasms appear as indirect signs of an underlying spasmogenic disease, such as G. I. tract carcinoid, pheochromocytoma, pancreatitis or poisoning such as ergotism or digitalis overdosage. Most of all, it may occur during some non-occlusive intestinal ischemias. On the other hand, spasm can be considered as a way of treatment, especially in cases of G. I. bleeding, particularly due to ulcerations.