Global warming and planetary health: An open letter to the WHO from scientific and indigenous people urging for paleo-microbiology studies.

This article, written by a collective of international researchers and worldwide representatives of indigenous populations, is an open letter to the WHO, based on the latest elements from the scientific literature, and the latest climatological data. It takes stock of the health consequences of global warming, and urges research organizations to take an interest in infectious agents formerly stored in the layers of ground (frozen or not) and now mobilized, then released from a distance.

A MSFD complementary approach for the assessment of pressures, knowledge and data gaps in Southern European Seas: The PERSEUS experience.

PERSEUS project aims to identify the most relevant pressures exerted on the ecosystems of the Southern European Seas (SES), highlighting knowledge and data gaps that endanger the achievement of SES Good Environmental Status (GES) as mandated by the Marine Strategy Framework Directive (MSFD). A complementary approach has been adopted, by a meta-analysis of existing literature on pressure/impact/knowledge gaps summarized in tables related to the MSFD descriptors, discriminating open waters from coastal areas. A comparative assessment of the Initial Assessments (IAs) for five SES countries has been also independently performed. The comparison between meta-analysis results and IAs shows similarities for coastal areas only. Major knowledge gaps have been detected for the biodiversity, marine food web, marine litter and underwater noise descriptors. The meta-analysis also allowed the identification of additional research themes targeting research topics that are requested to the achievement of GES.

Diversity, structure and function of fish assemblages associated with Posidonia oceanica beds in an area of the eastern Mediterranean Sea and the role of non-indigenous species.

Temporal and spatial variation in density, biomass and body size of littoral fish species associated with nearshore Posidonia oceanica meadows was studied over an annual cycle in an area of the eastern Mediterranean Sea. A total of 109,350 littoral fishes were collected, belonging to 34 families and 88 species. Density of fishes peaked during the summer due to high numbers of juveniles. Season was a significant factor determining density, although number of species and biomass did not show any obvious seasonal pattern. Throughout the study, schooling planktivorous fish species such as the picarel Spicara smaris, the bogue Boops boops and the damselfish Chromis chromis were dominant, both in terms of density (80%) and biomass (70%). Temporal variation in density and body size of fishes was used to assess the seasonal and ontogenetic habitat use of each species, with their affinity to seagrass assessed by comparing their respective distribution on sand. Four functional guilds were created (juvenile migrants, seagrass residents, seasonal migrants and occasional visitors) to describe the habitat use of P. oceanica meadows by each species. Several species associated with P. oceanica meadows used this habitat mainly as juveniles during summer, although many others were present concurrently as adults and as juveniles. Among the species encountered, 11 were non-indigenous of Indo-Pacific origin, of which three used seagrasses mainly as juveniles and four as residents. The non-indigenous silverstripe blaasop Lagocephalus sceleratus ranked among the 10 most dominant species in terms of biomass (2%) and was classified as a seagrass resident.

Interaction of cis-diamminedichloroplatinum(II) with sensitive and resistant L1210 cell lines. Drug binding to nuclei and DNA.

We used in parallel, to study the kinetics of cis-DDP cellular binding and distribution, a cL cell culture line established from L1210 murine leukemia ascites and its cLP derivative which acquired a 30-fold (ID50) resistance to cis-diamminedichloroplatinum(II). Cell cultures were incubated with 0.9 microgram/ml (3 microM) of the drug and after various incubation times up to 24 hr, the amount of platinum associated to whole cells, to isolated nuclei and to purified DNA was determined using atomic absorption spectrophotometry. For the first hours of incubation no significant difference in the rate of platinum association was observed between the two cell lines. After the first hours of incubation the amount of platinum associated to whole cells and to isolated nuclei was significantly higher in the drug sensitive cells. However, the rates of platinum association to the respective DNAs were quite similar in the two cell lines. Our study failed to demonstrate any significant quantitative modification of the overall drug-DNA association between the resistant and sensitive cell lines.

Interaction of cis-diamminedichloroplatinum (II) to chromatin. Specificity of the drug distribution.

We have studied the interaction of the antitumoral drug, cis-diamminedichloroplatinum (II), cis-DDP, to chromatin. Degradation of chromatin-platinum complexes with micrococcal nuclease releases the platinum bound to the linker DNA. By comparing the percentage of platinum released throughout the digestion to the percentage of acid-soluble DNA we suggest that the linker DNA is the preferential target for this drug. This is mainly the case when the amount of bound platinum is low (r less than 0.03) and is less at higher drug concentrations. By comparing the rate constants corresponding to the reaction of cis-DDP to chromatin, DNA or core particle it appears that these constants are the same. This indicates that the bound platinum is located mainly at the DNA level. Our results are discussed with respect to the structure of chromatin and we conclude that this structure should play a role in the in vivo association of cis-DDP to DNA.

Preliminary phase I clinical study and pharmacokinetics of (1,2-diaminocyclohexane) (isocitrato) platinum (II) or PHIC.

PHIC [NSC-350602; (1,2-diaminocyclohexane) (isocitrato) platinum (II)] is a new highly water-soluble platinum derivative. Preclinical studies showed antitumor activity on a wide range of tumors, no cross-resistance with cisplatin and little or no nephrotoxicity in mice and baboons. A phase I clinical trial was then initiated at doses of 300 mg/m2 infused intravenously over one hour without induced diuresis or hydration. Dosages were escalated up to 1500 mg/m2. A total of 29 patients received 52 courses of treatment. The most important side-effect is thrombocytopenia which is rapidly reversible. Nausea and/or vomiting were mild or moderate with onset 1 hr after the end of the infusion and seldom persisted beyond 24 hrs. Measurements of biological parameters did not reveal significant evidence of nephrotoxicity except in one patient who developed urinary tract infection and for whom hemodialysis became necessary. No change in the audiogram could be demonstrated. Peripheral neuropathy was documented in one patient, and in two other patients to whom morphine was given confusional episodes were observed. Although no antitumor effect was observed, there was apparent stabilization of disease. Pharmacokinetic parameters were calculated in twelve out of these 29 patients. Based upon total platinum plasma concentrations, the elimination half-life is 58.3 hrs and the plasma clearance is 21.2 ml/min with an apparent volume of distribution of 7.6 liters. However, considering both plasma concentrations and urinary excretion, we could estimate the half-life of free filterable species (60 min), the plasma clearance (125 ml/min) and the renal clearance (86 ml/min). Mean urinary excretion is 64.4% of the dose after 6 days and 53.1% at 24 hrs. Other administration protocols are suggested, based upon these pharmacokinetic parameters.

Pharmacokinetics of intra-arterial and intravenous cisplatin in head and neck cancer patients.

After administration of cisplatin (50 mg/m2 on days 1 and 2) by intra-arterial or intravenous infusions over 1 or 6 hr to a total of 24 patients with head and neck cancer, the main pharmacokinetic parameters of platinum were determined according to a multicompartmental analysis. Elimination half-life of total platinum is greater than 3 days, the amount of platinum recovered in the urine over 7 days accounting for 15-50% of the administered dose. The half-life of filterable platinum species was calculated from the urinary excretion data: 39 +/- 17 min (i.a./1 hr), 37 +/- 24 min (i.a./6 hr), 58 +/- 17 min (i.v./1 hr) and 51 +/- 22 min (i.v./6 hr). Biopsies of the tumor were also analyzed on day 3 for their platinum content. The mean concentrations of platinum in biopsies were: 2.72 micrograms/g (i.a./1 hr), 3.89 micrograms/g (i.a./6 hr), 1.27 micrograms/g (i.v./1 hr) and 1.38 micrograms/g (i.v./6 hr). Tumor regression, based upon clinical and histological data, was only moderate after this single chemotherapy course.