A comparison of surgical techniques for perineal wound closure following perineal excision: a systematic review and network meta-analysis.

BACKGROUND: To mitigate pelvic wound issues following perineal excision of rectal or anal cancer, a number of techniques have been suggested as an alternative to primary closure. These methods include the use of a biological/dual mesh, omentoplasty, muscle flap, and/or pelvic peritoneum closure. The aim of this network analysis was to compare all the available surgical techniques used in the attempt to mitigate issues associated with an empty pelvis. METHODS: An electronic systematic search using MEDLINE databases (PubMed), EMBASE, and Web of Science was performed (Last date of research was March 15th, 2023). Studies comparing at least two of the aforementioned surgical techniques for perineal wound reconstruction during abdominoperineal resection, pelvic exenteration, or extra levator abdominoperineal excision were included. The incidence of primary healing, complication, and/or reintervention for perineal wound were evaluated. In addition, the overall incidence of perineal hernia was assessed. RESULTS: Forty-five observational studies and five randomized controlled trials were eligible for inclusion reporting on 146,398 patients. All the surgical techniques had a comparable risk ratio (RR) in terms of primary outcomes. The pooled network analysis showed a lower RR for perineal wound infection when comparing primary closure (RR 0.53; Crl 0.33, 0.89) to muscle flap. The perineal wound dehiscence RR was lower when comparing both omentoplasty (RR 0.59; Crl 0.38, 0.95) and primary closure (RR 0.58; Crl 0.46, 0.77) to muscle flap. CONCLUSIONS: Surgical options for perineal wound closure have evolved significantly over the last few decades. There remains no clear consensus on the "best" option, and tailoring to the individual remains a critical factor.

The Impact of Federal and State Conservation Programs on Farmer Nitrogen Management.

The U.S. federal government, as well as many state and local governments, operate a number of conservation programs aimed at ameliorating the environmental problems associated with agriculture. While motives and barriers to conservation program participation and adoption of conservation practices have been extensively studied, the direct impacts of programs on ongoing farm operations remains underexplored. To examine the effects of conservation programs on nitrogen management, an aspect of crop production with significant environmental impacts we conducted interviews with 154 corn producers in three Midwestern U.S. states with a range of program experiences. We found that programs shifted farmer N management behavior through three social processes: (1) engaging farmers in the conservation system by introducing them to the state and federal conservation agencies, (2) incentivizing trialing of specific N management practices, and (3) increasing practice adoption through continued program engagement. Working-lands programs were far more effective at shifting on-farm nutrient management practices than land retirement, certification, or outreach-based programs, though all programs had the indirect benefit of increasing farmer familiarity with conservation agencies and programs. Working-lands programs directly motivated practice adoption; including soil testing regimes, implementing nutrient management plans, and splitting nitrogen applications to improving availability; by reducing producer risk and providing technical assistance, especially whole-farm planning. The additional benefits of all programs were moderated by participant selection bias, in particular that program participants were more predisposed to conservation efforts by existing stewardship and innovation attitudes.

Endometrial cancer cells can express fibrinogen: Immunohistochemistry and RT-PCR analysis.

We investigated whether endometrial cancer (EC) cells can express fibrinogen. Consecutive patients treated for EC were enrolled (cases). A control group of women who had hysterectomy for benign conditions was identified in a case:control ratio of 4:1. Immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) were performed to identify the presence of fibrinogen and the mRNA of its three chains (α, ß, γ) in the tissue specimens from both cases and controls. Sixteen EC cases and 4 benign controls were included. Immunohistochemistry failed in one case of EC. In 12/15 (80%) cases versus 0 controls, a moderate-to-intense positivity for fibrinogen was observed (p = 0.09; OR: 32.1; 95%CI: 1.4-752.9). Six (37.5%) women among the cases versus 0 controls expressed RNA for at least one chain of fibrinogen (p = 0.25). All the cases (6/6, 100%) with positive RT-PCR had moderate-to-intense positive immunohistochemistry. Molecular and immunohistochemistry show that some cases of EC have the capability to express fibrinogen and the mRNA of at least one of its chains.

Changing patterns in HIV-1 non-B clade prevalence and diversity in Italy over three decades.

BACKGROUND: HIV-1 non-B subtypes have recently entered Western Europe following immigration from other regions. The distribution of non-B clades and their association with demographic factors, over the entire course of the HIV-1 epidemic, have not been fully investigated in Italy. METHODS: We carried out a phylogenetic analysis of HIV-1 pol sequences derived from 3670 patients followed at 50 Italian clinical centres over nearly three decades. RESULTS: Overall, 417 patients (11.4%) carried non-B subtypes. The prevalence of non-B strains increased from 2.6% in 1980-1992 to 18.9% in 1993-2008 (P<0.0001) in a subset of 2479 subjects with a known year of diagnosis. A multivariate analysis on a subset of 1364 patients for whom relevant demographic data were available indicated that African ethnicity, heterosexual route of infection and year of diagnosis were independently associated with non-B HIV-1 infection (P ≤ 0.0001). All pure subtypes, except for clade K, and seven circulating recombinant forms were detected, accounting for 56.6 and 34.1% of the non-B infections, respectively. The F1 subtype was the most prevalent non-B clade among Europeans and was acquired heterosexually in half of this patient population. Unique recombinant forms accounted for 9.4% of the non-B sequences and showed a B/F1 recombination pattern in one-third of cases. CONCLUSIONS: The circulation of non-B clades has significantly increased in Italy in association with demographic changes. Spread of the F1 subtype and B/F recombinants appears to predominate, which may result in a redistribution of the relative proportions of the different strains, and this could lead to overlapping epidemics. Thus, the HIV-1 landscape in Italy may in future be distinct from that of the rest of Europe.

Evaluation of ammonia and odour emissions from animal slurry and digestate storage in the Po Valley (Italy).

Ammonia and odour emissions from one lagoon (Lagoon 1: pig slurry) and three tanks (Tank 2: cow slurry; Tank 3: digestate from pig slurry and energy crops; Tank 4: digestate from pig and cow slurries plus energy crop) used for slurry storage were sampled for two years (2015-2017) in livestock farms that differed for animal breeding and manure management (anaerobic digestion). On average, the ammonia emission rate (AER) was higher for Tank 3 (AER of 30.68 ± 28.1 g N-NH3 m-2 d-1) than for Lagoon 1 and Tank 2 and 4, i.e. 9.29 ± 14.89 gN-NH3 m-2 d-1, 9.38 ± 13.75 g N-NH3 m-2 d-1, 15.74 ± 21.91 g N-NH3 m-2 d-1, respectively. PLS regression analysis (R2 = 0.544; R2Adj. = 0.484) indicated that temperature was the main predictor of ammonia emitted, followed by concentration in the slurry of total ammonia and the relative percentage of volatile solids (VS). On the other hand, PLS analysis (R2 = 0.529, R2adj. = 0.417) indicated that odour emissions from animal slurry storages depended similarly upon total solids and VS (both referred to fresh weight) slurry contents, TAN/TKN ratio and degrees of biological stability (measured by anaerobic biogas potential - ABP), resulting in the Specific Odours Emission Rates (SOER) of 12,124 ± 7,914 and 35,207 ± 41,706 OUE m-2 h-1, 65,430 ± 45,360 and 43,971 ± 53,350 OUE m-2 h-1, for Lagoon 1 and Tanks 2, 3 and 4. These results suggest covering the tanks to limit both ammonia and odour emissions.

The role of policy in social-ecological interactions of nitrogen management in the Mississippi River basin.

Excess nitrogen (N) loading in the Mississippi River basin is a major water quality issue, encompassing large spatial scales and feedbacks between social and biophysical entities. Effective management depends on reductions in agricultural N loading, mainly from the Corn Belt region in the upper reaches of the basin. In this study, we evaluated the role of federal Nutrient Task Force policy on N management from 2000 to 2015. We analyzed trends in nitrate (NO3 - ) concentrations from monitoring data in 148 priority watersheds. We compared water quality trends with state nutrient reduction strategies, monitoring efforts, and land use. Of the 148 watersheds, 13 displayed a significant decrease in NO3 - concentrations, 24 displayed a significant increase, 51 displayed a nonsignificant trend, and 60 had insufficient data to analyze. We demonstrate that policy efforts on a large scale are slow to establish, but states and watersheds that showed signs of policy acting successfully could serve as examples for improved N management moving forward. Despite considerable variability, states with the most comprehensive strategies, evidenced by word count and presence of recommended elements, were almost exclusively located in the Corn Belt region. States with more thorough nutrient reduction strategies also tended to have a larger number of monitoring sites in priority watersheds (R = .42), demonstrating the potential for adaptive management. States with the most consistent improvements in NO3 - concentrations tended to have the most comprehensive policies, whereas variation in water quality trends was partly attributed to land use factors including slope and dominance of corn (Zea mays L.) and soy [Glycine max (L.) Merr.].

PI3KCA/PTEN deregulation contributes to impaired responses to cetuximab in metastatic colorectal cancer patients.

BACKGROUND: It has been reported that KRAS mutations (and to a lesser extent KRAS mutations with the BRAF V600E mutation) negatively affect response to anti-epidermal growth factor receptor (EGFR) mAbs in metastatic colorectal cancer (mCRC) patients, while the biological impact of the EGFR pathway represented by PI3K/PTEN/AKT on anti-EGFR treatment is still not clear. PATIENTS AND METHODS: We analysed formalin-fixed samples from a cohort of 32 mCRC patients treated with cetuximab by means of EGFR immunohistochemistry, EGFR and PTEN FISH analysis, and KRAS, BRAF, PI3KCA, and PTEN genomic sequencing. RESULTS: Ten (31%) of 32 patients showed a partial response to cetuximab and 22 (69%) did not [nonresponder (NR)]. EGFR immunophenotype and FISH-based gene status did not predict an anti-EGFR mAb response, whereas KRAS mutations (24%) and PI3K pathway activation, by means of PI3KCA mutations (13%) or PTEN mutation (10%)/loss (13%), were significantly restricted to, respectively, 41% and 37% of NRs. CONCLUSION: These findings suggested that KRAS mutations and PI3KCA/PTEN deregulation significantly correlate with resistance to cetuximab. In line with this, patients carrying KRAS mutations or with activated PI3K profiles can benefit from targeted treatments only by switching off molecules belonging to the downstream signalling of activated EGFR, such as mammalian target of rapamycin.

Blood velocity measurements in human retinal vessels.

Laser Doppler velocimetry was used to measure the velocity of blood in human retinal vessels. The mean flow velocities obtained were 1.9 centimeters per second in a retinal vein and 2.2 centimeters per second in a retinal artery. Scattered light from a weak helium-neon laser beam focused on the vessel was detected by a photomultiplier, and the temporal correlation of the intensity fluctuations was measured with a photon counting autocorrelator. Autocorrelation functions for blood flowing through glass capillaries were used for calibration.

Inherited cancer syndromes in 220 Italian ovarian cancer patients.

BACKGROUND: A subsets of ovarian carcinomas (OCs) are related to inherited conditions including Hereditary Breast and Ovarian Cancers (HBOC) and Lynch Syndrome (LS). The identification of inherited conditions using genetic testing might be a strategic model for cancer prevention that include benefits for the ovarian cancer patients and for their family members. METHODS: We describe a retrospective Italian experience for the identification of inherited conditions in 232 patients affected by OCs using both somatic and germline analyses. RESULTS: Immunohistochemical and microsatellite analyses performed on OCs identified 20 out of 101 MMR defective cancers and 15 of these were from patients carriers of the MMR germline pathogenetic variants. BRCA1 and BRCA2 testing offered to 198 OC patients revealed 67 (34%) pathogenetic variant carriers of BRCA1/2 genes. Interestingly LS patients revealed a mean age of OC onset of 45.4 years, which was significantly lower than the mean age of OCs onset of HBOC patients. CONCLUSIONS: Somatic and germline analyses offered to OC patients has proved to be an efficient strategy for the identification of inherited conditions involving OC also in absence of suggestive family histories. The identification of LS and HBOC syndromes through OC patients is an effective tool for OC prevention.

Organochlorine pesticide residues in sediment cores of sunderban wetland, northeastern part of Bay of Bengal, India, and their ecotoxicological significance.

This paper presents the first comprehensive report of the organochlorine pesticide residues (OCs) such as hexachlorocyclohexane isomers (HCHs), dichlorodiphenyltrichloroethane and its six metabolites (DDTs), and hexachlorobenzene (HCB) in core sediments (<63-microm particle size) from the Indian Sunderban wetland. The pooled mean values of the mass fraction of SigmaHCHs, HCB, and SigmaDDTs in the sediments were 0.05-12, 0.05-1.4, and 0.05-11.5 ng g(-1) dry weight, respectively. The vertical distribution of pesticides reveals an erratic pattern. The concentration of four isomers of HCHs reveals a heterogenic distribution where gamma-HCH (lindane) and beta-HCH shared the dominant part. The mass fraction of HCB did not show any sharp spatial variation. The prevailing sequence of DDT metabolites indicates an active degradation of the parent compound in the sediments and/or inputs of already degraded pp'DDT to the region. Peak concentrations of HCH isomers and DDT metabolites have the potential to induce ecotoxicological impact as per the sediment quality guidelines.

Anaerobic digestion coupled with digestate injection reduced odour emissions from soil during manure distribution.

This work aimed to measure the odour impact of untreated cow and pig slurries and treated (digestate and liquid fraction of digestate) manures when they were used on soil at a field scale, while also testing different spreading methods, i.e. surface vs. injection. Five experiments were performed in 2012-2016 on different farms. Odours were quantitatively (specific odour emission rate - SOER) (OUEm-2h-1) measured by using dynamic olfactometry and qualitatively, i.e. to obtain an "odour fingerprint", by using an electronic nose (EN). Anaerobic digestion was effective in allowing the reduction of potential odour emission from digestates, so that when they were dosed on soil, odours emitted were much lower than those from soils on which untreated slurries were used. Slurries/digestate injection reduced much more odour emitted by soils so that SOER tended to become more similar to that of the control (untreated soil) although the odours were slightly greater. Odour fingerprint data indicated that there was a direct correlation between SOER and odour fingerprints. This was due to the ability of EN to detect ammonia, S-compounds and methane that were (the first two mainly), also, responsible for odours. Very good regression was found for Log SOER and EN by using a Partial Least Square (PLS) approach (R2=0.73; R2cv=0.66; P<0.01) for matrices used to fertilize soils in lab tests. Unfortunately, regression was not so good when odour data from field experiments on soil were used, so that EN cannot be proposed to replace olfactometry. EN fingerprints for control (Blank) and injected organic matrices were virtually identical, due to the creation of cavities in the soil during the injection that decreased the treated surface. Anaerobic digestion and subsequent digestate injection allowed us to reduce odour impact, avoiding annoyance to local inhabitants.

Changes in optic nerve head blood flow in children with cerebral malaria and acute papilloedema.

OBJECTIVE: To investigate capillary blood flow in the optic nerve head (ONH) of children with cerebral malaria. METHODS: Malawian children with cerebral malaria admitted to a paediatric research ward were examined by direct and indirect ophthalmoscopy. ONH blood flow was measured using laser Doppler flowmetry (LDF) in suitable patients. Mean blood volume and velocity were obtained from 30 to 60 s recordings from the temporal ONH and used to calculate blood flow. These were compared with admission variables, funduscopic findings and disease outcomes. RESULTS: 45 children with cerebral malaria had LDF recordings; 6 subsequently died and 5 survivors had neurological sequelae. 12 (27%) had papilloedema. The mean microvascular blood volume was higher in patients with papilloedema (3.28 v 2.54 arbitrary units, p = 0.002). The blood velocity correlated directly with haematocrit (r = 0.46, p = 0.001) and inversely with blood glucose (r = -0.49, p = 0.001). CONCLUSION: The increase in ONH microvascular blood volume in papilloedema measured by LDF is consistent with current theories of pathogenesis of papilloedema. LDF has potential as a tool to distinguish papilloedema from pseudopapilloedematous disc swellings. The relationship between blood velocity and haematocrit may relate to levels of sequestration in cerebral malaria.

New evidences for old biomarkers: effects of several xenobiotics on EROD and AChE activities in Zebra mussel (Dreissena polymorpha).

The biomarker approach is widely used both in vertebrates and invertebrates for environmental biomonitoring, because it can supply an integrated response for multi-xenobiotics contamination. However, the use of biomarkers requires the identification of every possible variation that can influence the biochemical response, because ecosystems are generally subject to a mixture of pollutants, which can create additive, opposite or competitive effects. In recent years, there has been considerable interest in the use of biomarkers within marine bivalves, while very few data are available for freshwater molluscs. The aim of this research was to investigate changes on EROD and AChE activities in the freshwater bivalve Zebra mussel (Dreissena polymorpha) exposed to different pollutants (Arochlor 1260, CB 153 and 126, pp'DDT, chlorpyrifos, carbaryl) at laboratory conditions, in order to standardize the analytical procedures and to highlight eventual interferences on enzyme activities. Chemical concentrations in the mussel soft tissues were analyzed by GC/MS-MS. Main results showed a significant induction of EROD activity when mussels were exposed to 100 ng/l of PCB mixture of Arochlor 1260 and dioxin-like CB 126, but this congener showed also a clear competitive inhibition after 48 h of exposure. Surprisingly, pp'DDT determined a significant decrease of basal EROD activity after only 24 h of exposure, even if it was not possible to discriminate between the effect of the parent compound and that of its metabolites (DDD, DDE). We also found an interaction between the organophosphate insecticide chlorpyrifos, which does not directly decrease the AChE activity, and terbutilazine. This herbicide increased the biotransformation of the organophosphate compound to its oxidized metabolite (oxon), a much stronger AChE inhibitor. The possible use of the oxime Pyridine-2-Aldoxime Methochloride (2-PAM) to bring back the catalytic activity to basal levels was also demonstrated.

Sub-foveal choroidal blood flow by LDF: measurement and application to the physiology and pathology of the choroidal circulation.

Laser Doppler flowmetry allows the measurement of relative choroidal blood flow in the sub-foveal region of the fundus (ChBF). This technique has been applied to the investigation of the regulation of ChBF in response to a variety of physiological stimuli (breathing different gas mixtures of O2 and CO2, varying the systemic and ocular blood perfusion pressures, light-dark transition and zero gravity) in normal subjects. Measurements in pathological conditions, such as diabetes, age-related macular degeneration and glaucoma indicate alterations of the response of ChBF to increased systemic blood pressure. The data provide a better understanding of the regulation of the choroidal circulation in the normal and diseased eye.

1-beta-D-arabinofuranosylcytosine metabolism and incorporation into DNA as determinants of in vivo murine tumor cell response.

In this study, 1-beta-D-arabinofuranosylcytosine 5'-triphosphate (ara-CTP) formation, retention, and incorporation into DNA were simultaneously evaluated in vivo in mice bearing leukemia cells sensitive to 1-beta-D-arabinofuranosylcytosine (ara-C) (L1210/0), leukemia cells resistant to ara-C (L1210/R), P288, and lymphosarcoma P1798, namely cells characterized by differential sensitivity to ara-C. In L1210/R cells, resistance to ara-C was correlated with low deoxycytidine-cytidine kinase activity (0.04 nmol/mg protein/min), with a low level of intracellular accumulation of ara-CTP, with a low level of incorporation of ara-C into DNA, and with no significant inhibition of thymidine incorporation into DNA. Thus a simple measurement of the intracellular pool of total ara-C nucleotides is sufficient to identify cells with this type of resistance. In contrast, in cells with sufficient deoxycytidine-cytidine kinase activity (greater than 0.1 nmol/mg protein/min), the factors determining the quality of response to ara-C could be distinguished as follows: (a) those which are responsible for in vitro cytotoxicity (producing in vivo cytoreduction); and (b) those which are responsible for in vivo selectivity (producing long term survivors). In P288 cells which are sensitive in vitro to ara-C, the determining factor for this sensitivity is the amount of ara-CTP formed which produced greater than 80% inhibition of thymidine incorporation into DNA. The lack of antitumor activity in vivo, however, was due to similarities in ara-CTP retention in target tumor cells (P288) and normal bone marrow cells. In both cases, ara-CTP retention at 4 h was less than 10% of the value obtained at 30 min. In contrast, in cells such as L1210 and P1798 long term survivors (cures) were directly correlated with higher ara-CTP retention. For example, 4 h after drug administration, ara-CTP retentions were 20, 82, and 6% for L1210, P1798, and bone marrow cells, respectively. At 24 h, 20% ara-CTP was retained intracellularly by P1798 tumor cells. In summary, results presented herein demonstrate the importance of differential ara-CTP retention as the most critical determinant of response for the induction of long term survivors, and ara-C incorporation into DNA by tumor cells after in vivo treatment appears to be less significant. These data also demonstrate close correlation between ara-CTP pools, retention, and the extent of inhibition of recovery of thymidine incorporation into DNA.

Early involvement of 6q in surface epithelial ovarian tumors.

Complex karyotypes are often seen in primary surface epithelial ovarian tumors (SEOTs). Conventional cytogenetic as well as fluorescence in situ hybridization analyses coupled with loss of heterozygosity studies identified abnormalities of chromosome 6 as one of the most frequent lesions in these types of tumors. We performed cytogenetic analysis of direct preparations from 40 SEOTs, including borderline tumors and low-, intermediate-, and high-grade carcinomas to verify the frequency of chromosome 6 alterations. We also carried out fluorescence in situ hybridization analysis with a chromosome 6 library and yeast artificial chromosome clones from a region of the same chromosome (6q27). Chromosome 6 abnormalities were identified in 30 of 32 analyzable SEOTs. Twenty-five of 32 cases showed a deletion of 6q irrespective of their histological grade. We wish to underline that this is the first report proving that del(6q) was the most frequent chromosome anomaly in near-diploid SEOTs and that it was the sole anomaly observed in four SEOTs with diploid complement. Our findings suggest that abnormalities of the telomeric region of chromosome 6 (6q27) may be considered one of the earliest lesions in the pathogenesis of ovarian carcinomas.

Effects of dietary polyphenols on metabolic syndrome features in humans: a systematic review.

Dietary polyphenols constitute a large family of bioactive substances potential beneficial effect on metabolic syndrome (MetS). This review summarizes the results of clinical studies on patients with MetS involving the chronic supplementation of a polyphenol-rich diet, foods, extracts or with single phenolics on the features of MetS (obesity, dyslipidemia, blood pressure and glycaemia) and associated complications (oxidative stress and inflammation). Polyphenols were shown to be efficient, especially at higher doses, and there were no specific foods or extracts able to alleviate all the features of MetS. Green tea, however, significantly reduced body mass index and waist circumference and improved lipid metabolism. Cocoa supplementation reduced blood pressure and blood glucose. Soy isoflavones, citrus products, hesperidin and quercetin improved lipid metabolism, whereas cinnamon reduced blood glucose. In numerous clinical studies, antioxidative and anti-inflammatory effects were not significant after polyphenol supplementation in patients with MetS. However, some trials pointed towards an improvement of endothelial function in patients supplemented with cocoa, anthocyanin-rich berries, hesperidin or resveratrol. Therefore, diets rich in polyphenols, such as the Mediterranean diet, which promote the consumption of diverse polyphenol-rich products could be an effective nutritional strategy to improve the health of patients with MetS. © 2016 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity.

Short-term experiments in using digestate products as substitutes for mineral (N) fertilizer: Agronomic performance, odours, and ammonia emission impacts.

Anaerobic digestion produces a biologically stable and high-value fertilizer product, the digestate, which can be used as an alternative to mineral fertilizers on crops. However, misuse of digestate can lead to annoyance for the public (odours) and to environmental problems such as nitrate leaching and ammonia emissions into the air. Full field experimental data are needed to support the use of digestate in agriculture, promoting its correct management. In this work, short-term experiments were performed to substitute mineral N fertilizers (urea) with digestate and products derived from it to the crop silage maize. Digestate and the liquid fraction of digestate were applied to soil at pre-sowing and as topdressing fertilizers in comparison with urea, both by surface application and subsurface injection during the cropping seasons 2012 and 2013. After each fertilizer application, both odours and ammonia emissions were measured, giving data about digestate and derived products' impacts. The AD products could substitute for urea without reducing crop yields, apart from the surface application of AD-derived fertilizers. Digestate and derived products, because of high biological stability acquired during the AD, had greatly reduced olfactometry impact, above all when they were injected into soils (82-88% less odours than the untreated biomass, i.e. cattle slurry). Ammonia emission data indicated, as expected, that the correct use of digestate and derived products required their injection into the soil avoiding, ammonia volatilization into the air and preserving fertilizer value. Sub-surface injection allowed ammonia emissions to be reduced by 69% and 77% compared with surface application during the 2012 and 2013 campaigns.

Physical map of the D6S149-D6S193 region on chromosome 6Q27 and its involvement in benign surface epithelial ovarian tumours.

A detailed long range restriction map of the region defined by markers D6S149 and D6S193 on chromosome 6q27 has been constructed. This was achieved by YAC cloning and contig assembling of the same region. Seven YAC clones were found to span the almost 1000 Kb region flanked by the two markers which on the genetic map resulted to be 1.9 cM apart. With some of the characterized YAC clones we undertook a molecular cytogenetic analysis of 20 benign ovarian tumors. The rationale for this was the recent mapping to a region of chromosome 6q27, flanked by markers D6281 and D6S133, of a locus for the SV40-mediated immortalization of human cells (SEN6 gene). Noteworthy we found that the the D6S149-D6S193 region (comprised in the larger D6S281-D6S133 physical interval) was altered in all samples analysed adding support to the occurrence of a immortalization step in this type of tumors.

Atrial natriuretic peptide and prostacyclin synergistically mediate hyperfiltration and hyperperfusion of diabetic rats.

The relative contribution of atrial natriuretic peptide (ANP) and vasodilatory prostaglandins to hyperfiltration in Wistar rats with experimental diabetes was studied 6-8 wk after streptozocin injection. Plasma levels of immunoreactive ANP were significantly higher (P less than 0.01) in hyperglycemic diabetic (72.9 +/- 11.7 pg/ml) than in normoglycemic diabetic (44.8 +/- 8.6 pg/ml) or nondiabetic (40.0 +/- 6.8 pg/ml) rats. Blocking endogenous ANP by specific ANP-antiserum infusion reduced significantly (P less than 0.01) glomerular filtration rate (GFR) and renal plasma flow (RPF) of hyperglycemic rats compared with preinfusion values (1.23 +/- 0.06-1.02 +/- 0.04; 2.87 +/- 0.25-2.40 +/- 0.10 ml.min-1.100 g-1, respectively). However, correction of hyperfiltration and hyperperfusion was only partial (nondiabetic rats GFR 0.85 +/- 0.07; RPF 2.27 +/- 0.13 ml.min-1.100 g-1). Because diabetic rats with hyperglycemia also had an increased urinary excretion of prostacyclin metabolite 6-keto-prostaglandin F1 alpha (220.6 +/- 62.8 ng/24 h) compared with nondiabetic rats (51.2 +/- 2.7 ng/24 h), we wondered whether excessive prostacyclin formation contributed to hyperfiltration and hyperperfusion in this setting. Indomethacin infusion partially reduced GFR (1.25 +/- 0.07 to 1.06 +/- 0.07 ml.min-1.100 g-1, P less than 0.05) and RPF (2.85 +/- 0.11 to 2.46 +/- 0.12 ml.min-1.100 g-1, P less than 0.01) in diabetic rats. The combined infusion of ANP antiserum and indomethacin normalized GFR and RPF in diabetic rats with hyperglycemia (1.27 +/- 0.05 to 0.88 +/- 0.05 and 2.84 +/- 0.10 to 2.22 +/- 0.06 ml.min-1.100 g-1, respectively; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)