PFAS levels in fish species in the Po River (Italy): New generation PFAS, fish ecological traits and parasitism in the foreground.

Per- and polyfluoroalkyl substances (PFAS) are resistant to breakdown and are now considered ubiquitous and concerning contaminants. Although scientific and legislative interest in these compounds has greatly increased in recent decades, our knowledge about their environmental fate and their effects on organisms is still incomplete, especially those of the new generation PFAS. In this study, we analysed the level of PFAS contamination in the fish fauna of the Po River, the most important waterway in Italy, to evaluate the influence of different factors (such as fish ecological traits and parasitism) on the accumulation of 17 PFAS. After solvent extraction and purification, hepatic or intestinal tissues from forty specimens of bleak, channel catfish, and barbel were analysed by liquid chromatography coupled with mass spectrometry (LOQ = 2.5 ng/g w.w.). The prevalent PFAS were perfluorooctane sulfonate (PFOS), present in all samples at the highest concentration (reaching a maximum of 126.4 ng/g and 114.4 ng/g in bleak and channel catfish, respectively), and long-chain perfluoroalkyl carboxylic acids (PFDA and PFUnDA). Perfluorooctanoic acid and new generation PFAS (Gen X and C6O4) were not detected. Comparison of the hepatic contamination between the benthic channel catfish and the pelagic bleak showed similar concentrations of PFOS (p > 0.05) but significantly higher concentrations of other individual PFAS and of the sum of all measured PFAS (p < 0.05) in bleak. No correlation was found between the hepatic level of PFAS and fish size in channel catfish. For the first time, PFAS partitioning in a parasite-fish system was studied: intestinal acanthocephalans accumulated PFOS at lower levels than the intestinal tissue of their host (barbel), in contrast to what has been reported for other pollutants (e.g., metals). The infection state did not significantly alter the level of PFAS accumulation in fish, and acanthocephalans do not appear to be a good bioindicator of PFAS pollution.

Microplastics in cosmetics: Environmental issues and needs for global bans.

Despite the microbeads from cosmetic products do not contribute with high percentages to the microplastic pollution, they can pose a threat to the environment, being discharged into the water bodies and just partially blocked by the wastewater treatment plants. As environmental associations have been fighting for the abolition of microplastics in PCCPs, in many countries measures have been taken and bans are already operational or in process. Some cosmetic companies have voluntarily renounced the use of microbeads and some voluntary certifications of PCCPs prohibit their use. PCCPs recently analysed can contain levels of microbeads reaching 50,391 per g and can contribute with every single use to the introduction of 229,000 microbeads into the domestic sewage. Given the spread and danger of these pollutants, the problem is global and unthinkable to be solved by banning microplastic-containing products only in some countries, thus a general ban would be necessary.

Use of multiple cell and tissue-level biomarkers in mussels collected along two gas fields in the northern Adriatic Sea as a tool for long term environmental monitoring.

As a consequence of the growing global demand of energy supplies, intense oil and gas exploration and exploitation programs have been carried out worldwide especially within the marine environments. The release of oil-derived compounds in the sea from anthropogenic sources both as effluents or accidental spill is perceived as a major environmental concern. An approach based on a combination of biomarkers and the distribution of some classes of environmentally relevant pollutants was used to investigate the occurrence of a stress syndrome in mussels (Mytilus galloprovincialis) collected at three gas platforms placed in two distinct oceanographic districts within the Adriatic Sea. Biological responses were integrated by a ranking algorithm which demonstrated both a range of biological effects reflecting exposure gradients and a temporal related trend in the investigated responses. The overall results demonstrate a moderate to absent pollution from studied gas platforms with low but remarkable biological disturbance in sentinel organisms.

Assessment of environmental pollutants in ten southern Italy harbor sediments.

In 2003-2006, the distribution of macronutrients and pollutants of environmental interest was investigated in surficial sediments collected from 10 southern Italy harbors selected in four different regions. About 167 stations were sampled to determine levels of total organic carbon, total nitrogen, total phosphorous, trace elements (Al, Cd, Pb, Ni, Cr, Cu, Zn, Hg, As), short- and long-chain aliphatic hydrocarbons (Hy C > 12 and Hy C < 12), and concentrations of persistent organic pollutants (polychlorinated biphenyls, polycyclic aromatic hydrocarbons [PAHs], p-p-Dichlorodiphenyldichloroethylene (4,4'-DDE), and Hexachlorobenzene (HCB). General relationships between studied variables and harbors systems were explored by multivariate statistical approaches. Results show that wide fluctuations are reported for all variables both among harbors and inside each studied system. Principal components analysis suggests that major significance in explaining total average variability is due to lead, copper, zinc, silts, sands, and PAHs. No significance has been observed when testing nonmetric multidimensional scaling distributions relating with the factor "region," while performing analyses on factor "main human activity," a higher significance is observed. These results suggest a strong relationship between the main human use of marine systems and observed pollution levels in sediments.

Anthropogenic impacts on the Orbetello lagoon ecosystem.

The aim of the present study was to assess the environmental quality of Orbetello lagoon (Tyrrhenian coast, Italy), using a biomonitoring method based on measuring organochlorinated pollutants in the Anguilla anguilla, chosen as sentinel organism, and remote sensing data obtained by elaboration of Landsat 7 Enhanced Thematic Mapper (ETM) data of 2002. Polychlorinated biphenyls and organochlorine pesticides were determined by gas chromatography/mass spectrometry in muscle of European eels captured in seven sites having different levels of pollution in Orbetello lagoon. Remote sensing data and chemical analysis showed the Albegna river as a probable vehicle of pesticides (hexachlorocyclohexanes).

Twin pregnancy achieved through TESE in an adult male exstrophy.

Bladder exstrophy is a rare anomaly, it compromises bladder functions, and in males it occurs with an impairment of reproductive functions, because of erectile and ejaculatory deficit. Advancements in the surgical treatment of bladder exstrophy have allowed an improvement of the bladder functions while spontaneous conception is still impaired. This is a case report of a pregnancy and subsequent birth of twins following testicular sperm extraction, on a man born with classical bladder exstrophy with infertility due to an ejaculation.

[Fertilization in vitro and microinsemination. 6 years of experience in the Ospedale Microcitemico of Cagliari]. / Fecondazione in vitro e microinseminazione. Sei anni di esperienza nell'Ospedale Microcitemico di Cagliari.

BACKGROUND: In this study the results of six years experience (1993-1998) in IVF, ICSI and assisted hatching on 442 sterile couples for a total of 868 cycles are reported. Since 1997 ICSI has also been carried out in cases of azoospermia extracting mobile spermatozoa from the epididymal (MESA) or from the testicle (TESE). METHODS: Ages ranged from 20 to 48 and mean years sterility was 5.868 cycles were carried out of which 153 (17.62%) were for IVF, 705 (81.22%) for ICSI and 10 (1.15%) for MESA and TESE. Assisted hatching was performed through "partial zona dissection" in 329 cases on a total of 987 embryos. RESULTS: The pregnancy rates per embryo transfer in IVF and ICSI cycles were 22.4 and 19.96% respectively. Results considering patients age were: 33.87% below 35, 29.55% between 35 and 38 and 6.60% above 38. In the group of 189 assisted hatching patients the evolutive pregnancy rate rose from 15.78 to 26.40% and multiple pregnancies from 28.63 to 42%. CONCLUSIONS: ICSI has offered high rates of fertilization and pregnancy even in extreme cases of oligoasthenospermia or cases of azoospermia adopting MESA or TESE techniques. A decisive factor on pregnancy rates is age, very low over 38 years. Assisted Hatching further increased the pregnancy rates.

Glycosidopyrroles. Part 3. Effect of the benzocondensation on acyclic derivatives: 1-(2-hydroxyethoxy) methylindoles as potential antiviral agents.

The new of 1-(2-hydroxyethoxy)methylindole derivatives 3a-i were prepared in good yields. None of them showed any significant anti-HIV activity and therefore the benzocondensation between the 2 and 3 positions of the pyrrole ring definitely reduced the weak activity found in the analogues 1a-c.

Synthesis and biological evaluation of a series of substituted pyrazolo[3,4-d]-1,2,3-triazoles and pyrazolo[3,4-d]oxazoles.

In view of the biological relevance of triazole-based heterocyclic structures as antifungal, antiviral, and antitumor agents, we have synthesized a series of substituted pyrazolo[3,4-d]-1,2,3-triazoles (2e-h, 2j, 4b) which we evaluated for their cytostatic and antiviral (HIV-1 included) activity and for their capability to inhibit the multiplication of various human pathogenic fungi and bacteria. Moreover, the biological activities of a few compounds, namely pyrazolo[3,4-d]oxazoles (3a-e) and pyrazolo[3,4-d]-1,2,3-triazoles (2a-d, 4a, 5), previously obtained by us but not investigated for their biological activity, were also studied. Only compounds 3a-e were endowed with a significative antiproliferative activity on the human lymphoblastoid cell line MT-4 cells. All pyrazole derivatives proved ineffective in protecting cell cultures against the HIV-1-induced cytopathogenicity, and none of the compounds was active against the bacteria and fungi tested.

In vitro and in vivo antiproliferative activity of IPCAR, a new pyrazole nucleoside analog.

IPCAR is a pyrazole nucleoside analog which belongs to a class of compounds structurally related to the inosine monophosphate (IMP) dehydrogenase (IMPDH) inhibitors ribavirin, selenazofurin and tiazofurin. Unlike other anticancer drugs, IPCAR showed a potent and broad-spectrum antiproliferative activity in vitro coupled with low cytotoxicity for resting PBL and CFU-GM. IPCAR proved fully inhibitory against human nasopharyngeal carcinoma KB cells expressing the MDR phenotype, whereas IPCAR-resistant renal adenocarcinoma ACHN/R1 cells were fully susceptible to inhibition by a number of anticancer drugs, with the exception of 6TG, 6MP and 5FU towards which they showed a partial cross-resistance. In combinations studies, IPCAR proved synergistic with 6MP, 6TG, 5FU and ribavirin, and additive with ara-A, MTX, doxorubicin, taxol and tiazofurin. Antagonistic effects were never observed. Although the precise molecular target of IPCAR remains to be identified, the data presented herein suggest that, unlike ribavirin and tiazofurin, this drug inhibits a step of the de novo purine biosynthesis different from the conversion of IMP into GMP. In vivo, IPCAR showed low acute toxicity (DL10 > 1000 mg/kg) and was active against the L1210 murine lymphocytic leukemia model. Drug doses of 125 and 250 mg/kg on a day-1, -3 and -5 dosing schedule increased the life span (ILS) relative to untreated control mice of 36.4 and 68.2%, respectively, whereas administration of 500 mg/kg on days 1 and 3 resulted in a ILS of 86.4% and also increased the 30-day survival rate (25% of the mice).

Antitumor activity of 4,5,6,7-tetrathiocino (1,2-b: 3,4-b') diimidazolyl-1,3,8,10-tetrasubstituted-2,9-dithiones (R4-todit).

A series of derivatives belonging to a new class of compounds (R4-todit) were highly cytotoxic to a panel of leukaemia- and solid tumour-derived cell lines (IC50 = 0.06-20 microM). The most potent compound was the butyl4 derivative (IC50 = 0.06-5.1 microM); T leukaemia and melanoma cells were the most susceptible cells to this inhibitor (IC50 0.06 microM and 0.1 microM, respectively). The effect of butyl4-todit was irreversible, and led to progressive cell death. The compound showed a comparable potency against exponentially growing and stationary phase cells, and against cell lines expressing the MDR phenotype. The cytotoxicity of butyl4-todit in human normal PBL was up to 20 fold lower than that shown against T leukaemia cells. When tested for antiangiogenic activity in vivo, 1.5 mg/Kg butyl4-todit resulted in over 70% inhibition of the angiogenesis process induced in mice by Kaposi's sarcoma cell secreted products.

Traumatic aneurysms of the pericallosal artery in children. Case report.

Intracranial aneurysm in children is a rare pathology. Epidemiological studies have indicated that aneurysms in pediatric age are characterized by predominance in male subjects, a frequent great volume and a prevalently distal localization. It is assumed that these factors prove the traumatic origin (accident or birth) of the aneurysms. It is stressed that in juvenile subarachnoid hemorrhages the possibility of an aneurysm ought to be considered as an alternative to an arteriovenous malformation. A more extensive use of MR angiography is advocated in head injured patients, in order to diagnose an aneurysm before rupture. As a rule the outcome of surgical treatment is favorable provided the preoperative neurological status is not compromised.

Synthesis, structure, and antiproliferative activity of selenophenfurin, an inosine 5'-monophosphate dehydrogenase inhibitor analogue of selenazofurin.

The synthesis and biological activity of selenophenfurin (5-beta-D-ribofuranosylselenophene-3-carboxamide, 1), the selenophene analogue of selenazofurin, are described. Glycosylation of ethyl selenophene-3-carboxylate (6) under stannic chloride-catalyzed conditions gave 2- and 5-glycosylated regioisomers, as a mixture of alpha- and beta-anomers, and the beta-2,5-diglycosylated derivative. Deprotected ethyl 5-beta-D-ribofuranosylselenophene-3-carboxylate (12 beta) was converted into selenophenfurin by ammonolysis. The structure of 12 beta was determined by 1H- and 13C-NMR, crystallographic, and computational studies. Selenophenfurin proved to be antiproliferative against a number of leukemia, lymphoma, and solid tumor cell lines at concentrations similar to those of selenazofurin but was more potent than the thiophene and thiazole analogues thiophenfurin and tiazofurin. Incubation of K562 cells with selenophenfurin resulted in inhibition of IMP dehydrogenase (IMPDH) (76%) and an increase in IMP pools (14.5-fold) with a concurrent decrease in GTP levels (58%). The results obtained confirm the hypothesis that the presence of heteroatoms such as S or Se in the heterocycle in position 2 with respect to the glycosidic bond is essential for both cytotoxicity and IMP dehydrogenase inhibitory activity in this type of C-nucleosides.

Glycosidopyrroles. Part 2. Acyclic derivatives: 1-(1,3-dihydroxy-2-propoxy)methylpyrroles as potential antiviral agents.

The series of 1-(1,3-dihydroxy-2-propoxy)methylpyrroles 2a-o were prepared in good overall yields according to Scheme I. When evaluated for antiviral activity against HIV-1, only compounds of the triphenyl series (R3 = NH2, N3, Br) were found to inhibit the HIV-1 replication at concentrations that were very not cytotoxic for MT-4 cells, with selectivity index 1.5-9.3. None of these compounds showed antibacterial or antifungal activity.

Synthesis, antiviral and antiproliferative activity of a new class of 5-(alkyl or arylthio)-6-vinyl uracils.

Uracil derivatives bearing substituted or unsubstituted vinyl groups at position C6 and alkyl- or arylthio groups at position C5 were synthesized and tested in vitro for antiviral and antiproliferative activity. None of the compounds were active against HIV-1. However, some of them inhibited the proliferation of leukemia, lymphoma and solid tumor-derived cell lines at micromolar concentrations. The maximum potency of antiproliferative activity correlates with the presence of unsubstituted vinyl groups and alkyl- or arylthio substituents.

Release of dopamine in the ventral tegmental area of rat.

In this preliminary report we showed that 3,4-dihydroxyphenylacetic acid (DOPAC), the major metabolite of dopamine (DA), is present in the ventral tegmental area. This finding indicates that in the ventral tegmental area, which contains the cell bodies of dopaminergic neurons of the mesocortical and mesolimbic DA systems, DA may be released by a mechanism similar to that operating in the nerve endings. However, haloperidol, which increases DOPAC levels in the substantia nigra, failed to do so in the ventral tegmental area. The results support the contention that DA neurons in the ventral tegmental area have distinctive features from nigral DA neurones.