Laparoendoscopic single-site surgery for the assessment of peritoneal carcinomatosis resectability in patients with advanced ovarian cancer.

PURPOSE OF INVESTIGATION: To evaluate the feasibility, safety, and effectiveness of laparoendoscopic single site surgery (LESS) for the assessment of peritoneal carcinomatosis resectability in patients with advanced stage ovarian cancer (AOC). MATERIALS AND METHODS: The authors retrospectively reviewed the medical records of patients affected by advanced stage ovarian cancer who underwent LESS for operative work-up. A standard cytoreductive laparotomy surgery (CRS) was performed. RESULTS: Fifty-two women affected by AOC underwent LESS for operative work-up. The peritoneal cancer score was completed in 49 (94%) patients by use of LESS; 34/37 (92%) patients considered with a resectable disease were effectively optimally debulked and 15/52 (28%) patients considered with an unresectable disease received before neoadjuvant chemotherapy (NACT) and then underwent surgery. CONCLUSION: LESS is feasible, safe, and is an alternative minimally invasive procedure to assess the resectability of AOC patients.

P16INK4a as a progression/regression tumour marker in LSIL cervix lesions: our clinical experience.

PURPOSE OF INVESTIGATION: The aim of this prospective study was the evaluation of low-grade intraepithelial lesion (LSIL) lesions evolvement in woman with evidence of high risk HPV infection and p 16 4a negative expression. MATERIALS AND METHODS: 150 women with cytological diagnosis of LSIL were selected to be underwent to three years of follow-up consisting in smear test, colposcopy, and protein p16I4a investigation every six months and HPV-test every 12 months. RESULT: Final follow-up showed 45 cases of spontaneous lesion regression and 42 cases of persistence with absence of protein p164NK4a in all of them. There were three cases of disease progression to CIN2, two at 18-month follow-up and one at last follow-up. Disease progression was characterized of p16NK4a expression. CONCLUSION: p16l4a should help to identify which LSIL cases are inclined to the progression of the disease and focalize which patients are eligible for specific treatment.

Dental management in pregnancy: recent trends.

This review analyzes the changes that occur during normal pregnancy and describes the main odontogenic infections, suggesting the actual best approach in dental management. Several studies support the hypothesis that periodontal disease is associated with preterm labour and other conditions complicating pregnancy, such as pre-eclampsia and fetal growth restriction. Appropriate dental care and prevention during pregnancy may reduce poor prenatal outcomes and eliminating risk factors. Dental examination before pregnancy is strongly suggested in order to act early on dental and periodontal diseases. Prevention means reducing the presence of bacterial plaque through professional hygiene sessions, education, and motivation to proper oral hygiene at home, education in proper nutrition, a balanced diet, and low intake of sugars. For these reasons, it is essential to have a more intense interdisciplinary collaboration between gynecologist and dentist in order to achieve an optimal women's health, during this particular time in their lives.

Validating measures of free-living physical activity in overweight and obese subjects using an accelerometer.

BACKGROUND: Free-living physical activity can be assessed with an accelerometer to estimate energy expenditure but its validity in overweight and obese subjects remains unknown. OBJECTIVE: Here, we validated published prediction equations derived in a lean population with the TracmorD accelerometer (DirectLife, Philips Consumer Lifestyle) in a population of overweight and obese. We also explored possible improvements of new equations specifically developed in overweight and obese subjects. DESIGN: Subjects were 11 men and 25 women (age: 41±7 years; body mass index: 31.0±2.5 kg m(-2)). Physical activity was monitored under free-living conditions with TracmorD, whereas total energy expenditure was measured simultaneously with doubly-labeled water. Physical activity level (PAL) and activity energy expenditure (AEE) were calculated from total energy expenditure and sleeping metabolic rate. RESULTS: The published prediction equation explained 47% of the variance of the measured PAL (P<0.001). PAL estimates were unbiased (errors (bias±95% confidence interval): -0.02±0.28). Measured and predicted AEE/body weight were highly correlated (r(2)=58%, P<0.001); however, the prediction model showed a significant bias of 8 kJ kg(-1) per day or 17.4% of the average AEE/body weight. The new prediction equation of AEE/body weight developed in the obese group showed no bias. CONCLUSIONS: In conclusion, equations derived with the TracmorD allow valid assessment of PAL and AEE/body weight in overweight and obese subjects. There is evidence that estimates of AEE/body weight could be affected by gender. Equations specifically developed in overweight and obese can improve the accuracy of predictions of AEE/body weight.

Systemic nickel allergy syndrome: epidemiological data from four Italian allergy units.

The prevalence of nickel hyper-sensitivity varies widely in different countries, nevertheless it is the leading cause of contact dermatitis. The presence of nickel in the diet (mainly plant foods) in some nickel-sensitive subjects can provoke/aggravate eczema and systemic contact dermatitis as well as cause extra-cutaneous symptoms (respiratory, gastrointestinal, neurological). These symptoms, correlated to the ingestion of nickel-containing foods and beverages, in nickel patch test positive individuals, defines the so called Systemic Nickel Allergy Syndrome (SNAS), a condition successfully treated by oral desensitization. Although numerous studies have investigated the prevalence of contact nickel allergy or addressed the relationship between nickel intake and onset of systemic symptoms, to our knowledge no epidemiological studies have attempted to estimate the prevalence of SNAS. Therefore, we decided to evaluate consecutive patients (1,696), afferent to four allergy units in Sicily, a region of southern Italy, from October 2010 to March 2011. SNAS was confirmed in 98 patients (5.78 percent) of the 1,696 studied, suggesting that this clinical entity may be an emergent allergological condition rather than an occasional finding. The most common symptoms complained of in our population were cutaneous (51 patients), gastrointestinal (87 patients) and other systemic clinical manifestations (37 patients). Furthermore, 16 out of the 98 SNAS patients (16.3 percent) presented IgE-mediated food allergy with a statistically significant association (X2=16.950; P<0.0001), therefore suggesting underlying cross-facilitating pathways. These findings need confirmation on wider populations but may help allergists to suspect, during common clinical practice, that cutaneous and extra-cutaneous symptoms may be referred to nickel intake and deserve specific in-depth investigation.

Cell culture models and animal models for studying the patho-physiological role of renal aquaporins.

Aquaporins (AQPs) are key players regulating urinary-concentrating ability. To date, eight aquaporins have been characterized and localized along the nephron, namely, AQP1 located in the proximal tubule, thin descending limb of Henle, and vasa recta; AQP2, AQP3 and AQP4 in collecting duct principal cells; AQP5 in intercalated cell type B; AQP6 in intercalated cells type A in the papilla; AQP7, AQP8 and AQP11 in the proximal tubule. AQP2, whose expression and cellular distribution is dependent on vasopressin stimulation, is involved in hereditary and acquired diseases affecting urine-concentrating mechanisms. Due to the lack of selective aquaporin inhibitors, the patho-physiological role of renal aquaporins has not yet been completely clarified, and despite extensive studies, several questions remain unanswered. Until the recent and large-scale development of genetic manipulation technology, which has led to the generation of transgenic mice models, our knowledge on renal aquaporin regulation was mainly based on in vitro studies with suitable renal cell models. Transgenic and knockout technology approaches are providing pivotal information on the role of aquaporins in health and disease. The main goal of this review is to update and summarize what we can learn from cell and animal models that will shed more light on our understanding of aquaporin-dependent renal water regulation.

Relationship between testosterone deficiency and cardiovascular risk and mortality in adult men.

Classic male hypogonadism is associated with known adverse effects including decreased libido, erectile dysfunction, osteoporosis, and changes in body composition. Recently, we have come to appreciate that reduction in serum testosterone (T) levels resulting from aging or chronic disease or androgen deprivation therapy (ADT) have consequences similar to those seen in classic male hypogonadism which include increased fat mass, decreased lean body mass, decreased muscle strength, and sexual dysfunction. These data suggest that low T levels may represent a newly recognized cardiometabolic risk factor. Therefore, we carried out a careful review of the literature, focusing on major turning points of research and studies which gave more important and controversial contribution to the cardiovascular role of T. Observational studies and clinical trials investigating the relationship between T levels and cardiovascular disease and mortality were identified byMedline search. The results were synthesized, tabulated, and interpreted. The aim of this review is to discuss the association between low T levels and adverse metabolic profile such as insulin resistance, metabolic syndrome, and diabetes. We will also investigate the potential mechanisms by which male hypogonadism, especially age related or induced by ADT, may increase cardio-metabolic risk. Finally we will detail the emerging relationship between low T and mortality in men addressing also the reverse hypothesis that low T has a protective role by turning off T-dependent functions.

Role of the TNFA -308G > A polymorphism in the genetic susceptibility to acne vulgaris in a Sicilian population.

BACKGROUND: Acne vulgaris is a common and clinically well-characterized skin disease that affects a great proportion of the general population and thus, is a major public health problem. The aim of the present study was to investigate whether TNFA -308 G > A polymorphism might be involved in the pathogenesis of acne in a population from Sicily. METHODS: A total of 74 patients with acne and of 88 healthy control subjects from Catania, Italy were examined in the present study. TNFA -308 G > A polymorphisms using the PCR-RFLP method were determined in DNA extracted from buccal swabs. RESULTS: When controls were compared to acne patients, their genotype distributions, respectively G/G: 64.3%, G/A: 35.7% and G/G: 74.0%, G/A: 26.0%, were shown to be different, although not statistically significant (p = 0.191). A significant protective association between the TNFA -308 GA genotype and acne in males (p = 0.027; OR95% CI: 0.288; 0.094-0.889) was shown. CONCLUSIONS: The present results suggest that TNFA -308 polymorphism may contribute to acne susceptibility, as suggested by the protective effect of the G/A phenotype in the males of the Sicilian cohort. Further studies in larger groups, investigating the TNFA -308G/A or other polymorphisms of this gene in acne patients may be helpful to clarify the pathogenesis of the disease.

Lovastatin-induced cholesterol depletion affects both apical sorting and endocytosis of aquaporin-2 in renal cells.

Vasopressin causes the redistribution of the water channel aquaporin-2 (AQP2) from cytoplasmic storage vesicles to the apical plasma membrane of collecting duct principal cells, leading to urine concentration. The molecular mechanisms regulating the selective apical sorting of AQP2 are only partially uncovered. In this work, we investigate whether AQP2 sorting/trafficking is regulated by its association with membrane rafts. In both MCD4 cells and rat kidney, AQP2 preferentially associated with Lubrol WX-insoluble membranes regardless of its presence in the storage compartment or at the apical membrane. Block-and-release experiments indicate that 1) AQP2 associates with detergent-resistant membranes early in the biosynthetic pathway; 2) strong cholesterol depletion delays the exit of AQP2 from the trans-Golgi network. Interestingly, mild cholesterol depletion promoted a dramatic accumulation of AQP2 at the apical plasma membrane in MCD4 cells in the absence of forskolin stimulation. An internalization assay showed that AQP2 endocytosis was clearly reduced under this experimental condition. Taken together, these data suggest that association with membrane rafts may regulate both AQP2 apical sorting and endocytosis.

Histamine treatment induces rearrangements of orthogonal arrays of particles (OAPs) in human AQP4-expressing gastric cells.

To test the involvement of the water channel aquaporin (AQP)-4 in gastric acid physiology, the human gastric cell line (HGT)-1 was stably transfected with rat AQP4. AQP4 was immunolocalized to the basolateral membrane of transfected HGT-1 cells, like in native parietal cells. Expression of AQP4 in transfected cells increased the osmotic water permeability coefficient (Pf) from 2.02 +/- 0.3 x 10-4 to 16.37 +/- 0.5 x 10-4 cm/s at 20 degrees C. Freeze-fracture EM showed distinct orthogonal arrays of particles (OAPs), the morphological signature of AQP4, on the plasma membrane of AQP4-expressing cells. Quantitative morphometry showed that the density of OAPs was 2.5 +/- 0.3% under basal condition and decreased by 50% to 1.2 +/- 0.3% after 20 min of histamine stimulation, mainly due to a significant decrease of the OAPs number. Concomitantly, Pf decreased by approximately 35% in 20-min histamine-stimulated cells. Both Pf and OAPs density were not modified after 10 min of histamine exposure, time at which the maximal hormonal response is observed. Cell surface biotinylation experiments confirmed that AQP4 is internalized after 20 min of histamine exposure, which may account for the downregulation of water transport. This is the first evidence for short term rearrangement of OAPs in an established AQP4-expressing cell line.

Tetrameric assembly of CHIP28 water channels in liposomes and cell membranes: a freeze-fracture study.

Channel forming integral protein of 28 kD (CHIP28) functions as a water channel in erythrocytes, kidney proximal tubule and thin descending limb of Henle. CHIP28 morphology was examined by freeze-fracture EM in proteoliposomes reconstituted with purified CHIP28, CHO cells stably transfected with CHIP28k cDNA, and rat kidney tubules. Liposomes reconstituted with HPLC-purified CHIP28 from human erythrocytes had a high osmotic water permeability (Pf0.04 cm/s) that was inhibited by HgCl2. Freeze-fracture replicas showed a fairly uniform set of intramembrane particles (IMPs); no IMPs were observed in liposomes without incorporated protein. By rotary shadowing, the IMPs had a diameter of 8.5 +/- 1.3 nm (mean +/- SD); many IMPs consisted of a distinct arrangement of four smaller subunits surrounding a central depression. IMPs of similar size and appearance were seen on the P-face of plasma membranes from CHIP28k-transfected (but not mock-transfected) CHO cells, rat thin descending limb (TDL) of Henle, and S3 segment of proximal straight tubules. A distinctive network of complementary IMP imprints was observed on the E-face of CHIP28-containing plasma membranes. The densities of IMPs in the size range of CHIP28 IMPs, determined by non-linear regression, were (in IMPs/microns 2): 2,494 in CHO cells, 5,785 in TDL, and 1,928 in proximal straight tubules; predicted Pf, based on the CHIP28 single channel water permeability of 3.6 x 10(-14) cm3/S (10 degrees C), was in good agreement with measured Pf of 0.027 cm/S, 0.075 cm/S, and 0.031 cm/S, respectively, in these cell types. Assuming that each CHIP28 monomer is a right cylindrical pore of length 5 nm and density 1.3 g/cm3, the monomer diameter would be 3.2 nm; a symmetrical arrangement of four cylinders would have a greatest diameter of 7.2 nm, which after correction for the thickness of platinum deposit, is similar to the measured IMP diameter of approximately 8.5 nm. These results provide a morphological signature for CHIP28 water channels and evidence for a tetrameric assembly of CHIP28 monomers in reconstituted proteoliposomes and cell membranes.

A multicenter open-label experience on the response of psoriasis to Adalimumab and effect of dose escalation in non-responders: the Aphrodite project.

There is much evidence to show the efficacy of adalimumab, a human monoclonal antibody targeting tumour necrosis factor-alpha, in the treatment of plaque psoriasis. In this open-label experience, 147 high-need patients suffering from plaque psoriasis, with a mean Psoriasis Area and Severity Index (PASI) of 18.8, and concomitant psoriatic arthritis (PsA) received subcutaneous injections of 40 mg of adalimumab every other week (EOW). This was actually the dosage regimen recommended for PsA, as the drug had not then been approved for psoriasis at the time of the patients enrolment. At week 12, an improvement of at least 50 percent of the PASI (PASI-50) was observed in 111 (77 percent) patients. Continuation of treatment in responders with adalimumab 40 mg EOW led to a sustained response, with the PASI-50 achieved by 97 percent of patients in the as-treated analysis at week 24 (PASI-75 in 82 percent and PASI-90 in 45 percent out of 109 patients who received EOW injections up to week 24). Thirty subjects who failed to attain the PASI-50 response at week 12 were treated with adalimumab 40 mg every week for a further 12 weeks. At week 24, 80 percent of these patients obtained a PASI-50 response after dose escalation. Tolerability was good in the majority of patients. Only two patients discontinued treatment because of an adverse event (repeated flu-like episodes and a pleuropericarditis of unknown origin, respectively).

Dehydroepiandrosterone sulfate and cognitive function in the elderly: The InCHIANTI Study.

DHEA and its sulfate derivative (DHEAS) decline with age. The decline in DHEAS levels has been associated with many physiological impairments in older persons including cognitive dysfunction. However, data regarding the possible relationship between DHEAS and cognition are scant. We investigated whether DHEAS levels are associated with presence and development of lower cognitive function measured by the Mini Mental State Examination (MMSE) in older men and women. One thousand and thirty-four residents aged > or =65 yr of the InCHIANTI Study with data available on DHEAS and MMSE were randomly selected. MMSE was administered at baseline and 3 yr later. Among these, 841 completed a 3-yr follow-up. Parsimonious models obtained by backward selection from initial fully-adjusted models were used to identify independent factors associated with MMSE and DHEAS. The final analysis was performed in 755 participants (410 men and 345 women) with MMSE score > or =21. A significant age-related decline of both DHEAS levels (p<0.001) and MMSE score (p<0.001) was found over the 3-yr follow-up. At enrolment, DHEAS was significantly and positively associated with MMSE score, independently of age and other potential confounders (beta+/-SE 0.003+/-0.001, p<0.005). Low baseline DHEAS levels were predictive of larger decline of MMSE and this relationship was significant after adjusting for covariates (beta+/-SE -0.004+/-0.002, p<0.03). Our data show a significant and positive association between DHEAS and cognitive function, assessed by MMSE test. Low DHEAS levels predict accelerated decline in MMSE score during the 3-yr follow-up period.

Aquaporin 2 and apical calcium-sensing receptor: new players in polyuric disorders associated with hypercalciuria.

The kidney plays a critical role in regulating water homeostasis through specific proteins highly expressed in the kidney, called aquaporins, allowing water permeation at a high rate. This brief review focuses on some nephropathies associated with impaired urinary concentrating ability and in particular analyzes the role of aquaporin 2 in hypercalciuria, the most common metabolic abnormality in patients with nephrolithiasis. Specifically, this review discusses the relationship between hypercalciuria and impaired aquaporin 2-mediated water handling in both acquired and inherited disorders characterized by hypercalciuria, including those affecting the sensor of extracellular calcium concentration, the calcium-sensing receptor, which represents the principal target for extracellular calcium regulation of several tissues including parathyroid glands and kidney. In the kidney, the calcium-sensing receptor regulates renal calcium excretion and influences the transepithelial movement of water and other electrolytes. Understanding the molecular basis of alteration of kidney concentrating ability found in hypercalciuria will help for devising strategies for reducing the risk of nephrocalcinosis, nephrolithiasis, and renal insufficiency.

Sex hormone binding globulin levels across the adult lifespan in women--the role of body mass index and fasting insulin.

SHBG is a major carrier of androgens. In men, SHBG levels increase with age, while in women data are scant. There is evidence that body mass index (BMI) and fasting insulin influence SHBG concentration. Since low SHBG levels are predictors of insulin resistance and diabetes, understanding the relationship of SHBG with age, insulin, and BMI is important to gain insight into the role of SHBG as a cardiovascular risk factor in women. Differences in SHBG across adult life span and their relationship with insulin and BMI were evaluated in a representative cohort of 616 Italian women free of diabetes and not on hormone replacement therapy enrolled in the InCHIANTI Study. The relationship of SHBG with age, BMI, and fasting insulin levels was analyzed using linear regression and by loess smoother. Serum SHBG levels showed a U-shaped trajectory with age, declining from the 2nd to the 6th decade of life and increasing after the 6th decade (p<0.0001). Age-related trends for BMI and fasting insulin mirrored the trend observed for SHBG. After adjusting for fasting insulin, the relationship between log (SHBG) and age square was attenuated (beta coefficient from 0.00044 to 0.00039) and was further reduced after adjustment for BMI (from 0.00039 to 0.00028). SHBG levels show an age-related U-shaped trajectory. These changes mirror the age-related changes in BMI and fasting insulin, suggesting that BMI and insulin negatively influence SHBG concentration.

Water immersion is associated with an increase in aquaporin-2 excretion in healthy volunteers.

Here, we report the alterations in renal water handling in healthy volunteers during a 6 h thermoneutral water immersion at 34 to 36 degrees C. We found that water immersion is associated with a reversible increase in total urinary AQP2 excretion.

Expression of aquaporin-4 in fast-twitch fibers of mammalian skeletal muscle.

In this study we analyzed the expression of aquaporin-4 (AQP4) in mammalian skeletal muscle. Immunohistochemical experiments revealed that affinity-purified AQP4 antibodies stained selectively the sarcolemma of fast-twitch fibers. By immunogold electron microscopy, little or no intracellular labeling was detected. Western blot analysis showed the presence of two immunopositive bands with apparent molecular masses of 30 and 32 kD specifically present in membrane fraction of a fast-twitch rat skeletal muscle (extensor digitorum longus, EDL) and not revealed in a slow-twitch muscle (soleus). PCR Southern blot experiments resulted in a selective amplification in EDL of a 960-bp cDNA fragment encoding for the full-length rat form of AQP4. Functional experiments carried out on isolated skeletal muscle bundle fibers demonstrated that the osmotic response is faster in EDL than in soleus fibers isolated from the same rat. These results provide for the first time evidence for the expression of an aquaporin in skeletal muscle correlated to a specific fiber-type metabolism. Furthermore, we have analyzed AQP4 expression in skeletal muscle of mdx mice in which a decreased density of orthogonal arrays of particles, a typical morphological feature of AQP4, has been reported. Immunofluorescence experiments showed a marked reduction of AQP4 expression suggesting a critical role in the membrane alteration of Duchenne muscular dystrophy.

Androgen deficiency in older men.

Androgen deficiency in older men can be related to age associated changes of neuro-endocrine mechanisms controlling the hormones secreted by the testis and adrenal cortex. We listed the clinical consequences of androgen deficiency at three different levels in three areas: somatic (body composition, glucidic and lipid metabolism, erythropoiesis), sexual and psychological (cognition and affectivity). Observational studies and randomized placebo controlled trials have been reviewed from medical literature. Testosterone, now preferentially administered as transdermal gel, and dehydroepiandrosterone represent two possible treatments. New compounds designed to target androgen receptors in specific tissues are promising options as anabolic agents.

Retroperitoneal well-differentiated liposarcoma presenting as an incarcerated inguinal hernia.

A 69-year-old man was admitted with a complaint of left irreducible inguinal mass. On surgical exploration no evidence of hernia was found and the inguinal floor was overwhelmed by a large lobulated mass, arising from the properitoneal fat, that involved the spermatic cord. The mass was partially removed, sparing the elements of cord. The transversalis fascia was repaired by direct suture and a polypropylene mesh was located above. The histopathological diagnosis was well differentiated-type liposarcoma with myxoid features. The liposarcoma is a malignant tumour of the adipose tissue that arises from the primitive mesenchymal cells. These neoplasms have been usually found in the soft tissues of limbs, trunk, mediastinum, retroperitoneum and occasionally in the spermatic cord. The clinical aspect is frequently a complaint of scrotal or inguinal painless mass, mimicking to an inguinal hernia and the diagnosis of tumor is performed mainly during surgery, as in our patient. In the case of a firm not reducible painless inguinal mass without signs and symptoms of bowel obstruction, an abdominal tumor with inguinal or scrotal extension should be suspected and preoperatively excluded. The US and CT scan may be helpful to plane a correct therapeutic strategy before intervention.

Highly sensitive electrochemiluminescence detection of a prostate cancer biomarker.

Prostate-specific membrane antigen (PSMA), a glycoprotein expressed in the prostatic epithelium endowed with enzymatic activity, is a very promising diagnostic marker for the early detection of prostate cancer. In this study, we report a novel electrochemiluminescence ELISA-like immunosensor based on carbon nanotubes and a highly specific sandwich immunoassay for the PSMA detection. To fabricate the device, an optically transparent electrode was modified with doubly functionalized multi-walled carbon nanotubes carrying amine groups and a monoclonal anti-PSMA antibody. Subsequently, to complete the sandwich immunosensing device, a second specific monoclonal anti-PSMA antibody was labelled with a electrochemiluminescent probe. Under optimized experimental conditions, the proposed sensing device exhibits a performance exceeding that of the state of-the-art in terms of the limit of detection (LOD) and limit of quantification (LOQ) as good as 0.88 ng mL-1 and 2.60 ng mL-1, respectively, in real complex samples such as cell lysates. In addition, the unique role of carbon nanotubes is also discussed by comparison with an analogue sensor assembled without the nanocarbon-based material.