Assessment of simple strategies for identifying undiagnosed diabetes and prediabetes in the general population.

BACKGROUND AND AIMS: The rising tide of diabetes mellitus (DM) and prediabetes (PDM) is urgently calling for strategies easily applicable to anticipate diagnosis. We assessed the effectiveness of random capillary blood glucose (RCBG), administration of a validated DM risk questionnaire, or the combination of both. MATERIALS AND METHODS: RCBG measurement and/or questionnaire administration were offered to all individuals presenting at gazebos organized during the World Diabetes Day or similar public initiatives on diabetes awareness. Subjects with suspicious DM or PDM were invited to the Diabetes Center (DC) for laboratory confirmation (fasting plasma glucose and HbA1c). RESULTS: Among 8563 individuals without known diabetes undergoing RCBG measurement, 341 (4%) had suspicious values. Diagnosis of DM was confirmed in 36 (41.9%) of the 86 subjects who came to the DC and PDM was found in 40 (46.5%). Among 3351 subjects to whom the questionnaire was administered, 480 (14.3%) had suspicious scores. Diagnosis of DM was confirmed in 40 (10.1%) of the 397 who came to the DC and PDM was found in 214 (53.9%). These 3351 subjects also had RCBG measurement and 30 out of them had both tests positive. Among them, 27 subjects came to DC and DM was diagnosed in 17 (63.0%) and PDM was found in 9 (33.3%). CONCLUSIONS: These data suggest that RCBG definitely outperforms the questionnaire to identify unknown DM and PDM. RCBG measurement, with questionnaire as an adjunctive tool, appears to be a simple, fast, and feasible opportunistic strategy in detecting undiagnosed DM and PDM.

Dietary exposure of juvenile female mice to polyhalogenated seafood contaminants (HBCD, BDE-47, PCB-153, TCDD): comparative assessment of effects in potential target tissues.

Fish represents source of nutrients and major dietary vehicle of lipophilic persistent contaminants. The study compared the effects of two legacy and two emerging fish pollutants (Hexabromocyclododecane HBCD; 2,2',4,4'-Tetrabromodiphenyl ether BDE-47; 2,2',4,4',5,5'-Hexachlorobiphenyl PCB-153; 2,3,7,8-Tetrachlorodibenzo-p-doxin TCDD) in juvenile female mice exposed through a salmon based rodent diet for 28 days (dietary doses: HBCD 199 mg/kg bw/day; BDE-47 450 µg/kg bw/day; PCB-153 195 µg/kg bw/day; TCDD 90 ng/kg bw/day). Dose levels were comparable to previously reported developmental Lowest Observed Adverse Effect Levels. None of the treatments elicited signs of overt toxicity, but HBCD increased relative liver weight. All compounds caused changes in liver, thymus and thyroid; spleen was affected by BDE-47 and PCB-153; no effects were seen in uterus and adrenals. Strongest effects in thyroid follicles were elicited by PCB-153, in thymus and liver by BDE-47. HBCD and BDE-47 induced liver fatty changes, but appeared to be less potent in the other tissues. HBCD, BDE-47 and TCDD increased serum testosterone levels and the testosterone/estradiol ratio, suggesting a potential involvement of pathways related to sex steroid biosynthesis and/or metabolism. The results support the role of toxicological studies on juvenile rodents in the hazard characterization of chemicals, due to endocrine and/or immune effects.

Toxicants exposures as novel zoonoses: reflections on sustainable development, food safety and veterinary public health.

The modern concept of zoonosis considers any detriment to the health and/or quality of human life resulting from relationships with (other) vertebrate or edible or toxic invertebrate animals. Whereas exposure to toxicants through foods of animal origin (a.o.) is a well-established issue, hereby we discuss it as novel zoonoses, from the standpoints of health implications as well as similarities and differences with classical zoonoses caused by biological agents. Novel toxicant-related zoonoses are linked with new issues in food safety, such as the environment-feed-food chain. In fact, the potential effect of the combined and repeated exposure to dietary toxicants is generally long-term and not readily discernible. Endocrine disrupting chemicals in staple foods of a.o. are discussed as a telling example of a food safety issue summing up critical points covered by the definition of sustainable development, also implicating health risks for generations to come. We suggest some critical points to implement the veterinary public health action in sustainable food safety, such as enhancement of Hazard Analysis and Critical Control Points systems for toxicological risk management.

Cystic echinococcosis and the Mediterranean Region: a long-lasting association.

Cystic echinococcosis (CE) is an important zoonosis in Italy and in the whole Mediterranean Region, as confirmed by the work by Ettore Biocca, whose contributions to the subject are reported in a summarised annex to the bibliography. The contribution to the understanding and control of CE are presented, with special emphasis on the socio-economic impact, on factors affecting the maintenance of CE in the Mediterranean Region, on the epidemiological situation and control measures, on the present status of epidemiological surveillance, on the control problems in normal and emergency situations, on health education and training. Also, the justifications of combined control programmes are discussed, which may be applied only in situations of peace and well-being.

Endocrine effects in the hazard assessment of drugs used in animal production.

Criteria of toxicological assessment are currently reviewed to ensure an adequate protection to susceptible groups, such as infants and children; in particular, concern arises about altered endocrine homeostasis in the developing organism, eliciting possible persistent effects such as reproductive disturbances and increased risk of tumours in target organs. Such items are obviously relevant also for veterinary drugs, whose main safety issue is potential lifetime exposure to residues. Two groups of chemicals, nitroimidazoles and imidazole antifungals, are reviewed as examples of the relevance of endocrine toxicity to the hazard assessment of compounds used in animal production. Nitroimidazoles are metabolized into genotoxic intermediates; in rodents they induce testicular toxicity and carcinogenicity. In particular, mammary neoplasms, mostly fibroadenomas, are consistently induced in rats as the most important effect in chronic studies; this may hint to possible endocrine-related mechanisms. Accordingly, evidences on other chemicals (e.g., triazines) show mammary tumorigenicity in rodents associated to hormonal alterations. In fact, nitroimidazoles affect synthesis of both pituitary and steroid hormones in vitro and rise progesterone and FSH levels in rats; also, limited clinical data in humans indicate endocrine-related effects. Overall, nitroimidazoles appear to affect the endocrine balance; however, the actual importance of such alterations, especially in regards to rat mammary tumours, has yet to be clarified. Imidazole antimycotics are broad-spectrum inhibitors of steroid synthesis; accordingly, diverse reproductive and developmental alterations are observed, depending on age and sex of animals exposed. Effects include pregnancy loss, delayed pup growth as well as reduced weight of androgen-dependent tissue; however, it is still difficult to identify the most susceptible biological phase. Overall the potential for inducing endocrine-related alterations should be carefully evaluated also for drugs used in animal production. A screening battery should produce a distinct fingerprint for each major endocrine activity, thus targeting longer-term tests (such as the two-generation study) on the most relevant endpoints. Moreover, the validation of molecular approaches would contribute to a biologically-based evaluation, by providing insights on such items as early effects and species-specificity.

[Alkylphenols: assessment of risks for aquatic ecosystems and for human health with particular reference to endocrine effects]. / Alchilfenoli: valutazione dei rischi per gli ecosistemi acquatici e per la salute umana con particolare riferimento agli effetti endocrini.

(Alkylphenols: evaluation of the risk to aquatic ecosystems and human health with reference to endocrine effects).--Endocrine disrupting chemicals (EDC) are a heterogeneous group of substances that can interfere with many endocrine functions. Their effects have been demonstrated in different taxa and they are suspected to affect human health. Alkylphenols are an important group of EDC. They are formed from the degradation of alkylphenol polyethoxylates in the environment or in the sewage treatment plants. They are generally characterized by a high bioconcentration factor (BCF) and accumulate both in sediments and aquatic species. Alkylphenols (APE) show estrogenic activity: studies on fish and rodents put into evidence on both reproductive and developmental effects. In a recent study, the levels of APE detected in seafood from the Adriatic Sea showed a no negligible human health risk for strong fish consumers.

Problems in testing and risk assessment of endocrine disrupting chemicals with regard to developmental toxicology.

Endocrine disrupting chemicals (EDCs) may affect mammalian development either indirectly (by impairing implantation, placental development, lactation, etc.) or directly, altering the maturation of target tissues. Current regulatory tests for reproductive/developmental toxicity should be carefully evaluated with regard to risk assessment of EDCs, considering hazard identification (are relevant endpoints being assessed?) and dose-response assessment (are sensitive NOEL/dose-response curves being provided?). Many in vitro and in vivo assays for sex steroid disruption are available; provided that the metabolic capacities of the assays are defined, they could be integrated in a sensitive battery for early detection of steroid-disrupting potentials. The screening battery should address further regulatory in vivo tests (e.g. what specific parameters have to be investigated). As regards dose-response, qualitative differences may be observed between lower and higher exposures, showing primary hormone-related effects and frank embryotoxicity, respectively. Other problems concern (a) the identification of critical developmental windows, according to hormone concentrations and/or receptor levels in the developing target tissues; (b) the potential for interactions between chemicals with common mechanism/target (e.g. xenoestrogens); (c) most important, besides sex steroids more attention should be given to other mechanisms of endocrine disruption, e.g., thyroid effects, which can be highly relevant to prenatal and postnatal development.

4-Hexylresorcinol as inhibitor of shrimp melanosis: efficacy and residues studies; evaluation of possible toxic effect in a human intestinal in vitro model (Caco-2); preliminary safety assessment.

Studies were performed on the efficacy, residues and in vitro enterocyte toxicity of 4-hexylresorcinol (4-HR), which could be utilized as an inhibitor of shrimp melanosis (black spot). Mediterranean sea shrimp (Parapaeneus longirostris) were treated with solutions of 4-HR in sea-water, at three different concentrations, 25, 50 or 100 mg/kg of shrimp, to test its antioxidative property. As a comparison a group of shrimp was treated with sodium metabisulphite (1 g/kg), while another group was left untreated. 4-HR showed a marked ability to inhibit or slow down melanosis (black spot) in shrimp; the most effective concentration was 100 mg/kg within an optimum period of 7 days but with effects up to the tenth day. During the first 5 days, 4-HR residues in the edible part of the shrimp showed a fast decrease in all three groups, going from initial average values of 20 mg/kg at 0 time, to 0.9 in the group treated at 25 mg/kg; from 42 to 1.8 mg/kg in the group at 50 mg/kg and from 85 to 1.9 mg/kg in the group at 100 mg/kg. In vitro studies on enterocyte-like Caco-2 cells did not indicate any cytotoxic effect up to a concentration of 50 micrograms/ml. Moreover, no inhibition of protein synthesis was observed, which lends further support to the absence of significant damage to the intestinal mucosa induced by 4-HR. The available database on 4-HR pharmacology and toxicology is inadequate to determine even a provisional ADI. There is negative evidence of carcinogenesis and no significant untoward effects were observed in humans when it was used as an anthelmintic. However, it is not possible to determine a NOEL for non-genotoxic effects. 4-HR could become an interesting alternative to the use of sulphites to prevent black spot. However, a more complete database is needed to achieve a regulatory evaluation.

[Effects of chemical mixtures on embryonic development: examples of experimental models and problems in risk assessment]. / Effetti tossici di miscele chimiche sullo sviluppo prenatale: esempi di modelli sperimentali e problemi relativi alla valutazione del rischio.

Toxicological risk deriving from the exposure to mixtures of toxic substances, the study of possible interactions among them and their mechanisms of action are of special interest in prenatal toxicology. In fact, embryo is a dynamic complex system whose gradual development substantially modulates the extent and type of damages to which it may be sensitive, through specific, critical periods of sensitivity. In this paper, a number of types of interactions among toxic substances which show the same mechanisms of action and/or the same target site, are analysed. Besides, pharmacokinetic interactions among teratogenic agents and substances modulating their metabolism, need specific evaluations because of the wide variability of possible events. In conclusion, risk assessment in prenatal toxicology has to put greater attention to the various types of effect and pharmacokinetic interaction since they might result in an increasing risk at low doses.

Flow cytometric and histological assessment of 1,2:3,4-diepoxybutane toxicity on mouse spermatogenesis.

The effects of diepoxybutane (DEB) on mouse reproductive cells have been investigated by flow cytometric and histological description of testicular cell populations and alterations of sperm chromatin packaging. Mice were treated with single intraperitoneal injections of DEB, with doses ranging between 8.5 and 78 mg/kg (100-900 microM), and were killed after 7, 14, 21, 28 or 35 d. Dose-dependent reductions of tetraploid cells, round spermatids, and elongated spermatids were detected at 7, 21, and 28 d, respectively, reflecting cytotoxic damage on the differentiating spermatogonia compartment. The dose necessary to reduce the number of differentiating spermatogonia to half the control value was estimated equal to 650 microM or 55 mg/kg. Stem cells were not affected by this treatment. Histological section of seminiferous tubules showed depletion of spermatids and reduction of the secondary spermatocyte layers. In addition, a high although not statistically significant frequency of sperm with altered chromatin packaging was detected after DEB treatment. DEB is one of the key metabolites of butadiene, which is a compound of high environmental and occupational concern. These results contribute to the assessment of the reproductive health impact of butadiene in humans.

The role of multigeneration studies in safety assessment of residues of veterinary drugs and additives.

Multigeneration studies investigate the impact of a chemical on the reproductive function of laboratory rodents following continuous exposure of several (usually 3) generations. Such tests detects the presence of effects sensitively and efficiently; however, it may be necessary to add satellite groups to the basic protocol and/or to undertake more specific studies in order to investigate the nature of the effects observed. The possible enhancement of the chemical's impact along the generations and the use of apical endpoints (fertility, pup mean weight and survival, etc.) make multigeneration tests apt to reveal the cumulative action of minor, detrimental hits. Therefore, they appear especially important in the safety assessment of chemicals not expected to be markedly toxic, like many veterinary drugs or feed additives. The present paper reviews the role played by the data drawn from multigeneration studies in the toxicological evaluation of six compounds, namely: a) a synthetic anabolic steroid with hormonal (antigonadotropic) activity, trenbolone acetate; b) a colouring additive with some cumulative toxicity, canthaxanthin; c) a lipophyllic drug with effects on neuron transmission, ivermectin; d) a teratogenic benzimidazole, albendazole; e) a genotoxic molecule, olaquindox; f) a drug with male reproductive toxicity, closantel. Finally, the endpoints evaluated in the multigeneration studies might be utilized also in field studies aimed at evaluating the long-term reproductive impact of chemicals in farm species.

Notes on the use of animals for monitoring of human health hazards.

Motivations and perequisites for the use of animals for monitoring human health hazards are discussed. Tetanus, histoplasmosis, cryptococcosis and fluorine and lead intoxications are reported as examples.