Localized morphea after breast implant for breast cancer: A case report.

PURPOSE: Early breast cancer follow-up guidelines for patients who underwent surgery suggest a regular and accurate clinical examination of the breast area, for an early identification of cutaneous or subcutaneous breast cancer relapse. Nonetheless, breast skin lesions arising in patients treated with mastectomy for breast cancer can be caused by several diseases. A series of diagnostic hypotheses should be considered, not only focusing on cutaneous metastasis, but also on dermatologic and systemic diseases. CASE REPORT: In February 2015, a 37-year-old patient underwent a right subcutaneous mastectomy for stage IIA breast cancer. Five months after beginning adjuvant chemotherapy, she noted hyperpigmentation and thickening of the skin on the right breast. Differential diagnosis included local relapse, skin infection, lymphoma, or primary cutaneous disease, and a skin biopsy was performed. The histopathologic specimen showed full-thickness sclerosis, with features of localized morphea. Therapy with clobetasol was prescribed, with progressive resolution of the thickness. The collaboration between many professionals in a multidisciplinary team (oncologist, dermatologist, plastic surgeon, and pathologist) was crucial to achieving the diagnosis. CONCLUSION: In the literature, some articles describe correlation between connective tissue diseases and silicone breast implants, but the pathogenetic mechanisms are unknown. We report a rare case of breast morphea after positioning a silicone implant in a patient who had undergone mastectomy. This clinical report represents an interesting model of multidisciplinary management of a patient with breast cancer who developed an uncommon dermatologic disease. Further studies are needed to clarify the association between silicone implants and breast morphea.

Development of an ecotoxicological protocol for the deep-sea fauna using the hydrothermal vent shrimp Rimicaris exoculata.

In light of deep-sea mining industry development, particularly interested in massive-sulphide deposits enriched in metals with high commercial value, efforts are increasing to better understand potential environmental impacts to local fauna. The aim of this study was to assess the natural background levels of biomarkers in the hydrothermal vent shrimp Rimicaris exoculata and their responses to copper exposure at in situ pressure (30MPa) as well as the effects of depressurization and pressurization of the high-pressure aquarium IPOCAMP. R. exoculata were collected from the chimney walls of the hydrothermal vent site TAG (Mid Atlantic Ridge) at 3630m depth during the BICOSE cruise in 2014. Tissue metal accumulation was quantified in different tissues (gills, hepatopancreas and muscle) and a battery of biomarkers was measured: metal exposure (metallothioneins), oxidative stress (catalase, superoxide dismutase, glutathione-S-transferase and glutathione peroxidase) and oxidative damage (lipid peroxidation). Data show a higher concentration of Cu in the hepatopancreas and a slight increase in the gills after incubations (for both exposed groups). Significant induction of metallothioneins was observed in the gills of shrimps exposed to 4µM of Cu compared to the control group. Moreover, activities of enzymes were detected for the in situ group, showing a background protection against metal toxicity. Results suggest that the proposed method, including a physiologically critical step of pressurizing and depressurizing the test chamber to enable the seawater exchange during exposure to contaminants, is not affecting metal accumulation and biomarkers response and may prove a useful method to assess toxicity of contaminants in deep-sea species.

Early effects of diabetes on inducible nitric oxide synthase in the kidney.

NO may be responsible for the glomerular hyperfiltration observed in diabetic kidney by inducing vasodilation of the afferent arteriole. The aim of this study was to evaluate which isoform of nitric oxide synthase (NOS) is responsible for increased renal production of NO in diabetic kidney. Thirty male WKY rats were divided into 6 groups. Five rats were sacrificed immediately, five after 20 days. In the other rats, diabetes was induced by streptozotocin. The four diabetic groups were sacrificed respectively after 5, 10, 15 and 20 days. Urine excretion of NO metabolites was assayed; immunochemistry showed the presence of inducible (iNOS) and endothelial constitutive (ecNOS) synthases in the kidney. Urinary excretion of NO metabolites increased significantly in diabetic rats five days after the induction of diabetes and at the end of the study whereas it was unchanged in the control group. Renal ecNOS remained unchanged throughout the study in all rats whereas iNOS increased significantly in diabetic rats from the fifth day until the end of the study. The results demonstrate that iNOS is activated in the kidney of rats, soon after the induction of diabetes, thus suggesting its involvement in the increased production of NO observed immediately after the onset of diabetes.

A novel polymer produced by a bacterium isolated from a deep-sea hydrothermal vent polychaete annelid.

AIMS: The objective of the present work was to describe an aerobic, mesophilic and heterotrophic marine bacterium, designated HYD657, able to produce an exopolysaccharide (EPS). It was isolated from a East Pacific Rise deep-sea hydrothermal vent polychaete annelid. METHODS AND RESULTS: This micro-organism, on the basis of the phenotypical features and genotypic investigations, can be clearly assigned to the Alteromonas macleodii species and the name A. macleodii subsp. fijiensis biovar deepsane is proposed. Optimal growth occurs between 30 and 35 degrees C, at pH between 6.5 and 7.5 and at ionic strengths between 20 and 40 g x l(-1) NaCl. The G + C content of DNA was 46.5%. This bacterium excreted, under laboratory conditions, an EPS consisting of glucose, galactose, rhamnose, fucose and mannose as neutral sugars along with glucuronic and galacturonic acids and a diacidic hexose identified as a 3-0-(1 carboxyethyl)-D-glucuronic acid. Its average molecular mass was 1.6 x 10(6) Da. CONCLUSIONS: The bacterium HYD657, for which the name A. macleodii subsp. fijiensis biovar deepsane is proposed, produces an unusual EPS in specific medium. SIGNIFICANCE AND IMPACT OF THE STUDY: Due to its interesting biological activities, applications have been found in cosmetics. Its probable contribution to the filamentous microbial mat in the Alvinella pompejana microenvironment can be also mentioned.

Antihypertensive treatment with enrasentan (SB217242) in an animal model of hypertension and hyperinsulinemia.

Enrasentan is an antagonist of endothelin (ET) receptors. Previous studies have shown that antagonism of ET receptors might represent a new approach to the treatment of hypertension. Rats with a high-fructose diet (HFD) develop hyperinsulinemia, hypertriglyceridemia, and hypertension; renal and cardiac damage. The aim of this study was to evaluate whether enrasentan could reverse the hypertension and reduce the target organ damage induced by an HFD. Fifty-five WKY rats were divided into 6 groups; 35 animals received HFD for a month; thereafter 5 animals were killed, and the others were treated either with enrasentan (n = 10), hydralazine (n = 10), or placebo (n = 10) for a further month while on the HFD. Twenty animals were kept on a standard diet throughout the study; either placebo (n = 10) or enrasentan (n = 10) was administered during the second month. Enrasentan and hydralazine completely eliminated the HFD-induced increase in blood pressure; however, only enrasentan reduced the renal and cardiac damage caused by the diet. In conclusion, enrasentan was effective both in normalizing blood pressure and in reducing renal and cardiac damage; the organ protection cannot be attributed solely to the antihypertensive effect, because it was absent in the case of hydralazine, despite successful control of blood pressure.

Caloranaerobacter azorensis gen. nov., sp. nov., an anaerobic thermophilic bacterium isolated from a deep-sea hydrothermal vent.

A thermophilic, anaerobic, chemo-organotrophic bacterium, designated MV1087T, was isolated from a deep-sea hydrothermal chimney sample collected from the Mid-Atlantic Ridge. The cells were straight, motile and stained gram-negative. Growth was observed from 45 to 65 degrees C, with an optimum around 65 degrees C. No growth was observed at 40 or 70 degrees C. Growth was observed from pH 5.5 to 9.0 and the optimum pH was around 7. The salinity range for growth was 10-100 g sea salt l(-1) (corresponding to 6.5-65 g NaCl l(-1)) with an optimum at 30 g sea salt l(-1) (20 g NaCl l(-1)). Strain MV1087T was heterotrophic, able to ferment proteinaceous substrates, such as brain/heart infusion and gluten, and carbohydrates, such as glucose, xylan and starch. The DNA G+C content was 27 mol%. Phylogenetic analyses using 16S rDNA sequences indicated that strain MV1087T belonged to cluster XII of the Clostridium subphylum. Due to its phenotypic and genotypic characteristics, isolate MV1087T is proposed as a novel species of a new genus, Caloranaerobacter azorensis gen. nov., sp. nov. The type strain is MV1087T (= CNCM I-2543T = DSM 13643T).

Marinitoga camini gen. nov., sp. nov., a rod-shaped bacterium belonging to the order Thermotogales, isolated from a deep-sea hydrothermal vent.

A thermophilic, anaerobic, chemo-organotrophic sulfur-reducing bacterium, designated MV1075T, was isolated from a deep-sea hydrothermal chimney sample collected on the Mid-Atlantic Ridge. Cells were rod-shaped with a sheath-like outer structure, motile with polar flagella and stained Gram-negative. They appeared singly, in pairs or in short chains. The temperature range for growth was 25-65 degrees C, with an optimum at 55 degrees C. Growth was observed from pH 5 to pH 9, and the optimum pH was around 7. The salinity range for growth was 15-70 g sea salt l(-1) (corresponding to 10-45 g NaCl l(-1)), with an optimum at 30 g l(-1) (20 g NaCl l(-1)). The isolate was able to grow on a broad spectrum of carbohydrates or complex proteinaceous substrates. Sulfur was not necessary for growth. Growth was inhibited by H2, but, in presence of sulfur, this inhibition was removed and H2S was produced. The G+C content of the genomic DNA was 29 mol %. Phylogenetic analyses of the 16S rRNA gene located the strain within the order Thermotogales, in the domain Bacteria. On the basis of 16S rDNA sequence comparisons, in combination with morphological and physiological characteristics, it is proposed that the isolate should be described as a novel species of a new genus, Marinitoga gen. nov., of which Marinitoga camini sp. nov. is the type species. The type strain is MV1075T (= CNCM 1-2413T = DSM 13578T).

Microbial diversity in smoked salmon examined by a culture-independent molecular approach--a preliminary study.

Microbial biodiversity in sliced vacuum-packed cold smoked salmon was investigated using culture-independent molecular biology techniques. Sliced smoked salmon was stored for 25 days after being packed at 4 degrees C. DNA was extracted from sliced vacuum-packed cold smoked salmon. PCR DNA amplification were carried out using universal eubacterial primers corresponding to Escherichia coli 16S rRNA gene. 16S rRNA genes were amplified, cloned in E. coli and compared using Amplification Ribosomal DNA Restriction Analysis (ARDRA). 106 clones were studied and classified into 13 Operational Taxonomic Units (OTUs). Sequences obtained to describe those 13 OTUs were compared to GenBank data. They indicated the presence of Vibrio species. Enterobacteraceae and also marine psychrophilic clones related to Alteromonas macleodii, which were not encountered within cultures, but no Gram-positive species have been obtained. Those results indicate that bias in description of microbial diversity may be encountred in both molecular and cultural techniques.

Cloning, expression, and characterization of DNA polymerase I from the hyperthermophilic archaea Thermococcus fumicolans.

The DNA polymerase I gene of a newly described deep-sea hydrothermal vent Archaea species, Thermococcus fumicolans, from IFREMERS's collection of hyperthermophiles has been cloned in Escherichia coli. As in Thermococcus litoralis, the gene is split by two intervening sequences (IVS) encoding inteins inserted in sites A and C of family B DNA polymerases. The entire DNA polymerase gene, containing both inteins, was expressed at 30 degrees C in E. coli strain BL21(DE3)pLysS using the pARHS2 expression vector. The native polypeptide precursor of 170kDa was obtained, and intein splicing as well as ligation of the three exteins was observed in vitro after heat exposure. The recombinant enzyme was purified and some of its activities were characterized: polymerization, thermostability, exonuclease activities, and fidelity.

Unilateral adrenal hypersecretion of both aldosterone and cortisol in two first cousins with a syndrome of mineralocorticoid excess but without signs of hypercortisolism.

A 38 year old woman and her first cousin, a 41 year old man, presented both with hypertension, hypokalemia, hyperaldosteronism, and low plasma renin activity in our Hospital. In both patients, plasma and urine aldosterone were constantly above the normal range, even on a high NaCl diet (250 mEq/day), while the plasma aldosterone response to postural changes was normal. In the female patient abdominal ultrasonic scan, CT scan, MRI, and adrenal gland phlebography were normal, but blood from the left adrenal vein contained 1002 pg/ml of aldosterone, versus 91 pg/ml in the contralateral one. Interestingly, the secretion of cortisol was also lateralized (plasma cortisol levels being of 28.8 mcg% in the left, 2.3 mcg% in the right adrenal gland), although neither clinical nor laboratory signs of hypercortisolism were present. Spironolactone treatment (100 mg/daily) completely reversed the syndrome of mineralocorticoid excess. After 2 years, patient has normal blood pressure and serum K+ levels.

Selective expansion of cytotoxic T lymphocytes with a CD4+CD56+ surface phenotype and a T helper type 1 profile of cytokine secretion in the liver of patients chronically infected with Hepatitis B virus.

Highly purified CD4+ T cells isolated from liver biopsies of patients with hepatitis B virus-induced CAH had a strong cytotoxic activity and were comprised of a substantial number of cells (25%-40%) expressing CD56 surface marker. These cells were absent in CD4+ T cells from the peripheral blood of CAH patients or normal controls and these suspensions did not have cytotoxic activity. CD4+CD56+ T cells were further characterized by studies at the clonal level. A total of 71 hepatitis B envelope antigen-specific CD4+ T cell clones was investigated (23 from liver biopsies, 48 from peripheral blood of patients or normal vaccinated individuals). A total of 16 out of 23 (69.5%) of the clones from liver biopsies, but only 4.1% (2 out of 48) of those from PBLs, expressed CD56. A clone was defined as CD56+ when 40% or more of the cells expressed the marker. Production of TNF-alpha, IL-4, IL-5, IL-2, and IFN-gamma was investigated in 15 CD4+CD56+ and in 18 CD4+CD56- T cell clones, which shared the same HLA restriction element (DR2w15) and the same fine specificity (peptide 193-207 of the S region). All of the clones from the two groups released TNF-alpha and IL-2. However, all of the CD4+CD56+ T cell clones produced IFN-gamma but not IL-4 and IL-5 (Th1-like cell clones). Fourteen of the CD4+CD56- clones released IFN-gamma, IL-4, and IL-5 (Th0-like cell clones); three produced IL-4 and IL-5 but not IFN-gamma (Th2-like cell clones); and only one had a Th1 cytokine secretion profile. Cell fractionating studies within single CD4+CD56+ T cell clones showed that cells expressing high density CD56 had a stronger cytotoxic activity and produced higher levels of IFN-gamma than cells with low density CD56, thus further supporting a correlation between CD56 expression and cell functions. The results indicate that: 1) in CAH patients, cytotoxic CD4+ T cells with a Th1 cytokine secretion profile are compartmentalized in the liver, 2) these cells may be identified by the expression of CD56, 3) the expansion of these cells may be facilitated by antigenic stimulation within the inflammatory environment of the liver, and 4) CD4+CD56+ cells may play a pathogenetic role in hepatitis B virus infection.

[Pulmonary hypertension and systemic sclerosis]. / Ipertensione polmonare e sclerosi sistemica.

BACKGROUND: Pulmonary involvement in systemic sclerosis (SS) is a frequent complication and is associated with a poor prognosis. Pulmonary hypertension may or may not develop, however, its recognition is usually possible only in advanced stages. METHODS: In this study we noninvasively evaluated the pulmonary artery systolic pressure in 31 patients with SS using Doppler echocardiography. Pulmonary hypertension was detected in 48.4% of the patients. RESULTS: The prevalence of pulmonary hypertension was similar in patients with limited SS and diffuse SS (42.9% and 52.9%, respectively; p = NS). No differences were observed in pulmonary artery systolic pressure between patients with limited or diffuse SS and pulmonary hypertension. Pulmonary hypertension was usually mild, and only in two cases was pulmonary systolic pressure higher than 50 mmHg (63 and 107 mmHg, respectively). CONCLUSIONS: Pulmonary hypertension is frequently observed in patients with SS. The patients with diffuse or limited SS are equally affected by this complication. Doppler echocardiography has proved to be the technique of choice for the evaluation of pulmonary involvement in patients with SS because it is noninvasive, inexpensive and allows serial examinations. Early recognition of pulmonary hypertension may favor the use of therapeutical strategies to prevent the progression to advanced forms.

Enhanced blood pressure response to cyclooxygenase inhibition in salt-sensitive human essential hypertension.

To evaluate the influence of salt sensitivity on the blood pressure response to oral indomethacin treatment, we studied 35 hospitalized essential hypertensive patients (24 men and 11 women, aged from 40 to 55 years). During a normal NaCl intake (120 mmol Na+ per day), patients were assigned to receive in a randomized double-blind fashion either 200 mg indomethacin (25 patients) or placebo (10 patients) for 5 days. Two weeks after the interruption of indomethacin treatment, during which the normal NaCl intake was continued, salt sensitivity was assessed by giving each patient a high (220 mmol Na+ per day for 10 days) and then a low (20 mmol Na+ per day for 10 days) NaCl diet. Blood pressure changes were evaluated, and the measurement taken at the end of the 2 weeks under normal sodium intake was considered baseline blood pressure. Patients were classified as salt sensitive when a diastolic blood pressure change of 10 mm Hg or more occurred after both low and high periods of sodium intake. In salt-resistant patients treated with indomethacin (n = 12, nine men and three women, mean age 50.5 +/- 3.7 years), neither blood pressure (systolic blood pressure from 150.8 +/- 11.2 to 154.6 +/- 9.3 mm Hg, NS; diastolic blood pressure from 99.3 +/- 2.1 to 101.1 +/- 4.4 mm Hg, NS) nor the urinary Na+ excretion (from 108.1 +/- 20.9 to 97.9 +/- 9.1 mmol/24 hr, NS) was significantly affected by the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Octreotide, a somatostatin analog, reduces insulin secretion and increases renal Na+ excretion in lean essential hypertensive patients.

The influence of insulin on renal Na+ excretion is still subject to debate. In order to evaluate the effect of insulin suppression on Na+ excretion, 20 never-treated essential hypertensive men and 8 normotensive men were studied. All subjects had a body mass index < 27 kg/m2. Both the glucose and the lipid metabolisms were normal. After 2 weeks under normal NaCl intake (120 mEq NaCl daily), either octreotide, a somatostatin analog, or vehicle were infused in a forearm vein during acute volume expansion (0.30 mL/kg/min isotonic saline given intravenously over a period of 30 min). A double-blind randomized cross-over design was followed, and each subject was given both infusions at a 1 week interval. Blood and urine samples were taken at times--60, 0, 30, 60, 90, 120, 180, 240, and 300 min. Our data showed that octreotide significantly lowered insulin levels in both hypertensives (from 12.2 +/- 2.4 microU/mL at time 0 to undetectable values at time 30 and 60 min) and normotensives (from 11.5 +/- 2.8 microU/mL at time 0, to undetectable values at time 30 and 60 min). Compared to saline infusion alone, octreotide significantly increased Na+ excretion in both hypertensives and normotensives (saline + octreotide v saline alone = P < .05 at time 60 and 90 min). In conclusion, octreotide enhanced the natriuretic response to intravenous Na+ load in both hypertensives and normotensives. The increase in urinary Na+ was accompanied by a significant decrease in plasma insulin levels.

Geographical clustering of scleroderma in a rural area in the province of Rome.

A geographical cluster of scleroderma and scleroderma-related features was identified in a rural area in the province of Rome. Two patients with scleroderma, three with CREST syndrome and one with eosinophilic fasciitis were living in a village where the total population included 572 persons of voting age. No kindred relationships were demonstrable among these patients. Clinical features of scleroderma such as Raynaud's phenomenon, bilateral hand edema, and digital scars were detected in an additional 10 cases. A group of apparently healthy subjects with scleroderma-related serological abnormalities (circulating antinuclear and anticentriole autoantibodies) was also identified in the village. No disease-associated HLA antigen in the patients nor genetic differences between patients and healthy subjects living in the same village were detected by HLA typing. Some still unidentified environmental factors acting on genetically predisposed subjects may be responsible for the clustering of the disease seen in this study.

Normalization of depressed natural killer activity after interferon-alpha therapy is associated with a low frequency of relapse in patients with chronic hepatitis C.

In the present study, we found that human recombinant interferon-alpha (rIFN-alpha) given at a dose of 3 x 10(6) units thrice weekly for three months, and 1.5 x 10(6) units thrice weekly for the next three months, was able to restore depressed natural-killer (NK) activity to normal values in 12 out of 21 chronic hepatitis C patients positive for anti-HCV antibodies. In all of these patients, NK normalization was still sustained after three months from suspension of therapy. Eighteen patients also showed a normalization of the alanine aminotransferase (ALT) level by the end of treatment (responder patients), independently of changes in NK activity. No significant improvement in either NK activity or aminotransferase levels was seen among 20 untreated patients. In 8 responder patients (1 with normalized and 7 with low NK activity), ALT levels returned to pre-therapy values within three months after suspension of rIFN-alpha administration (relapse). We found that patients who normalized NK activity had a lower frequency of relapse as compared to patients with low NK activity by the end of treatment (p > 0.01). Immunofluorescence analysis of biopsy-derived liver tissue revealed that rIFN-alpha was able to induce strong MHC class I antigen expression on hepatocytes of treated patients, but this was not related to the clinical course.

Detection of replicative intermediates of viral RNA in peripheral blood mononuclear cells from chronic hepatitis C virus carriers.

Clinical and experimental evidence suggests the possible existence of one or more extrahepatic sites of HCV infection. In order to demonstrate the "in vivo" infection of lymphoid cells by HCV, we applied a nested PCR to total cytoplasmic RNA extracted from fresh or cultured peripheral blood mononuclear cells (PBMCs) of HCV chronically infected patients, using primers derived from the highly conserved 5' untranslated region of the HCV genome. The presence of virions in PBMCs occurs frequently, if not always, and is often accompanied by active viral replication. Moreover, the appearance of replicative intermediates after stimulation of cellular growth with mitogens suggests that latent genomes could undergo replication upon cellular activation and/or proliferation.

The influence of salt sensitivity on the blood pressure response to exogenous kallikrein in essential hypertensive patients.

In order to verify the influence of salt sensitivity on the blood pressure response to orally administered kallikrein, we evaluated the efficacy of glandular kallikrein (derived from porcine pancreas) in 28 essential hypertensives (21 males and 9 females) aged between 40 and 62 years. After a placebo run-in period, the patients were assigned to receive oral kallikrein therapy (150 IU 3 times a day; n = 18 patients) or placebo (n = 10 patients) over a period of 8 days in a random double-blind fashion. In the salt-resistant patients (n = 8), kallikrein administration did not modify blood pressure levels. In the same group, natriuresis increased significantly after the treatment [from 94.51 +/- 10.76 to 111.65 +/- 23.19 mEq/24 h (mmol/24 h), p < 0.039]. In the salt-sensitive patients (n = 10), blood pressure decreased with the kallikrein therapy (systolic: from 158.50 +/- 9.20 to 144.50 +/- 10.12 mm Hg, p < 0.005; diastolic: from 99.50 +/- 2.16 to 90.0 +/- 3.67 mm Hg, p < 0.024). In the same patients, urinary Na+ excretion increased considerably after the kallikrein treatment (from 101.07 +/- 18.36 to 134.34 +/- 18.27 mEq/24 h, p < 0.0001). Therefore, our data indicate that the oral kallikrein administration reduces blood pressure levels only in the salt-sensitive hypertensives. In both the salt-sensitive and the salt-resistant groups a marked increase in the 24-hour urinary excretion of sodium was observed after the kallikrein treatment.(ABSTRACT TRUNCATED AT 250 WORDS)