Benzo(a)pyrene (BaP), an aryl hydrocarbon receptor (AhR) ligand present in cigarette smoke and car exhaust, is thought to have negative effects on male reproduction. We hypothesized that BaP damages sperm through AhR activation, phase I enzyme induction, DNA adduct formation, and increased germ cell apoptosis in the testis, and that resveratrol, a natural competitive inhibitor of the AhR found in some red wines, could prevent the adverse effects of BaP on sperm. Male Balb C mice were injected subcutaneously (s.c.) for 5 weeks with a range of BaP doses (0.5 mg/kg to 50 mg/kg). Live sperm were obtained from the vas deferens, counted, and stained to measure annexin-V positive (apoptotic) cells. In a subsequent study, mice were injected for 5 weeks with corn oil (control), BaP (5 mg/kg/week), or BaP plus resveratrol (50 mg/kg/week) (n = 3 per group). Immunohistochemistry (IHC) was performed on testis sections for the determination of CYP1A1, BaP diol epoxide (BPDE) DNA adducts, and apoptosis and the results quantified by using the HSCORE, a semiquantitative scoring system. Our results demonstrated that sperm counts after 5 weeks were inversely correlated to BaP dosage. BaP (0.5 to 5 mg/week) positively correlated with sperm apoptosis while higher doses increased sperm necrosis. CYP1A1 protein was observed mainly in interstitial cells of some testis sections, but there was no significant induction by BaP. BPDE DNA adducts were induced in all components of the seminiferous tubules by BaP and suppressed by resveratrol: median HSCORE (interquartile range) control 61 (52-71.5); BaP 213 (192-248), P = 0.01 compared to control; BaP plus resveratrol 83 (70-90). BaP significantly increased apoptosis, mainly in spermatogonia: medain HSCORE (interquartile range) BaP 189 (161-223) versus control 83 (57-93), P < 0.01; and this effect was abrogated by resveratrol. Median HSCORE for BaP plus resveratrol was 112 (range 99-121). In summary, BaP caused increased sperm cell BPDE DNA adduct formation and apoptosis in the mouse. The natural AhR antagonist, resveratrol diminished BaP-induced DNA adducts and apoptosis in seminiferous tubules.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

PubMedDate not supplied

[Use of radionuclides in therapy].

INTRODUCTION: In nuclear medicine therapy is based on deposition of certain doses of ionizing radiation in tumors or organ tissues. Regarding their linear energy transfer (LET) values and relative biological effectiveness (RBE), principal radiotherapeuticals are alpha-, beta-, beta/gamma- or electron-emitters. In principle, to achieve the desired therapeutic effect, a particular radionuclide should exhibit adequate physical, chemical and biological properties. However, considerable efforts are required in selecting an optimal radionuclide for a specific application and then, in the development of methods for its routine production. THERAPEUTIC USE OF RADIONUCLIDES: The paper reviews several aspects of use, properties and production of unsealed radiation sources which are intended to be administered for therapeutic purposes. It covers scientific and practical criteria involved in selecting the radionuclide from medical point of view. The main indications for use of radiotherapeuticals are in oncology and rheumathology. Besides well known, like 32P, 89Sr, 90Y and 131I, several other radionuclides are also listed. Some of them are already in routine use while the others are still under investigation. The main chemical forms of radionuclides and indications are revealed. Particular emphasis is put on the discussion on criteria which a radionuclide should fulfill regarding its physical properties (type, energy, half life, ratio and abundance of the particulate and gamma ray emission). Ideally, they should, together with chemical and biological properties, match with the in-vivo pharmacokinetics and localization of the radionuclide and/or radiopharmaceutical. The trend in modern nuclear medicine is introduction of radionuclides of very specific properties. This, on the other side, opens a question of their availability on the routine basis and at reasonable prices. This matter is also discussed in the present review. CONCLUSION: Production of radionuclides for therapeutic purposes (as well as those for diagnostics) is performed either in nuclear reactors or in cyclotrons. Advantages and disadvantages of each production are discussed. The main nuclear reactions for routine production of 32P, 89Sr, 90Y and 131I are given, as well as for production of several other reactor or cyclotron-produced radionuclides. These are, e.g., reactor-produced beta-emitter 169Er, beta/gamma emitters 67Cu, 153Sm, 165Dy, 186Re and electron-emitters 80mBr and 125I. Generators for production of alpha emitters 212Bi and 213Bi are also under development. It can be concluded that, at present, besides 131I, large activities of 32P, 89Sr and 90Y are available on regular basis. For many others, routine availability remains yet to be established.

Humans↗

PubMedDate not supplied

[Iodine levels in salt for human consumption and aspects of iodine prophylaxis in Yugoslavia].

Iodine content of iodinated salt intended only for human consumption was eyamined in samples from all domestic manufacturers (salt mines in: Tuzla, Pag, Ulcinj, Ston, Nin, Seca-Portoroz). Sampling was made from commercially available packs (1 kg) or from food industries (large packs). It was established that iodine content of examined samples (57) varied considerably and ranged from 1.8 to 12.2 mg iodine/kg salt. Iodinated salt from the Tuzla and Pag salt mines contained iodine within the prescribed limits in both small and large packs. Similar finding of iodine content was in the small packs of the Ulcinj salt mines, however, their large packs (10 kg) had a markedly low level of iodine (1.8-4.7 mg). Lower iodine content was also noted in salts (1 kg) from the Nin, Ston and Seca-Portoroz mines. Of the 57 examined samples in 70% iodine content was lower than the prescribed dose (7.6 mg). In addition, some mines had low iodine content in all of the 100% of their respective samples. Ever since iodine prophylaxis was introduced in Yugoslavia a number of factors influenced the decrease of iodine intake by the organism to a considerable degree. The results of our investigations and some epidemiological data indicate that the issue of increasing the amount of iodine from the present 7.6 to 15 mg iodine/kg salt should be reconsidered. Besides, it is necessary to arrange the systematic quality control of iodinated salt.

Goiter↗

PubMedDate not supplied

[Serum antithyroid antibodies in patients with pernicious anemia].

We investigated the incidence of thyroid auto-antibodies and their relationship to antigastric antibodies in 20 euthyroid patients with pernicious anaemia. To evaluate possible thyroid dysfunction we also measured total level of thyroid hormones (TT3 and TT4) and TSH in our patients. Histologic evidence of autoimmune atrophic gastritis and intestinal metaplasia was obtained in 15 patients. We found that it was surprisingly high incidence of thyroid auto-antibodies in patients with pernicious anaemia, particularly in the group with intestinal metaplasia (antithyreoglobulin antibodies 71% and antimicrosomal antibodies 100%). The incidence of antigastric antibodies in these patients was similar to that of those with significant antithyroid antibodies (16/18). Total triiodo thyronine and TSH were significantly higher in the patients with pernicious anaemia than in the control group (p less than 0.05), in the normal range. The results of our study suggest that this upset in immunological physiology is due to a more generalized defect in immune tolerance.

Aged↗