Pesticide exposure: the hormonal function of the female reproductive system disrupted?

Some pesticides may interfere with the female hormonal function, which may lead to negative effects on the reproductive system through disruption of the hormonal balance necessary for proper functioning. Previous studies primarily focused on interference with the estrogen and/or androgen receptor, but the hormonal function may be disrupted in many more ways through pesticide exposure. The aim of this review is to give an overview of the various ways in which pesticides may disrupt the hormonal function of the female reproductive system and in particular the ovarian cycle. Disruption can occur in all stages of hormonal regulation: 1. hormone synthesis; 2. hormone release and storage; 3. hormone transport and clearance; 4. hormone receptor recognition and binding; 5. hormone postreceptor activation; 6. the thyroid function; and 7. the central nervous system. These mechanisms are described for effects of pesticide exposure in vitro and on experimental animals in vivo. For the latter, potential effects of endocrine disrupting pesticides on the female reproductive system, i.e. modulation of hormone concentrations, ovarian cycle irregularities, and impaired fertility, are also reviewed. In epidemiological studies, exposure to pesticides has been associated with menstrual cycle disturbances, reduced fertility, prolonged time-to-pregnancy, spontaneous abortion, stillbirths, and developmental defects, which may or may not be due to disruption of the female hormonal function. Because pesticides comprise a large number of distinct substances with dissimilar structures and diverse toxicity, it is most likely that several of the above-mentioned mechanisms are involved in the pathophysiological pathways explaining the role of pesticide exposure in ovarian cycle disturbances, ultimately leading to fertility problems and other reproductive effects. In future research, information on the ways in which pesticides may disrupt the hormonal function as described in this review, can be used to generate specific hypotheses for studies on the effects of pesticides on the ovarian cycle, both in toxicological and epidemiological settings.     

Analysis of tumor-associated alkyldiacylglycerols and other lipids during radiation-induced thymic leukemogenesis.

Lipid composition of thymuses investigated during the development of thymic leukemogenesis induced by exposing C57BL/6J mice to gamma radiation led to the following conclusions. 1. Alkyldiacylglycerols, a class of lipids that are generally elevated in most neoplastic tissues, occurred only in small quantities (less than 1% of the total lipids) in the thymuses of both control and irradiated mice. However, we found a 3- to 8-fold increase in this fraction in thymic tumors of mice at 5 mo after irradiation when compared to controls of similar age. However, the small quantity of this lipid class in thymic leukemia and the fact that similar levels were found in some samples of involuted thymuses of mice 3 days after irradiation, suggests to us that the level of alkyldiacylglycerols is not sufficiently specific or sensitive for detecting early stages of thymic leukemogenesis. 2. Thymuses 3 days after irradiation and leukemic thymuses contain 2- to 3-fold greater quantities of cholesterol esters than control thymuses. No major differences were found in the distribution of acyl moieties in the cholesterol esters of the various thymus samples from the same aged mice except that in thymic tumors the quantity of 18:1 esters was increased by about 25% over that of the controls. The apparent lack of specificity of increased cholesterol esters for neoplasia indicates that its measurement would not provide a suitable indicator of early neoplastic transformation. 3. Acyl composition of the triacylglycerols of thymuses revealed an increase in the 18:1 and a decrease in the 18:2 acids at 3 days after irradiation when compared to the same aged controls. However, thymic tumors occurring at 5 mo after irradiation contained less 14:0, 16:0, and 16:1 acids and increased amounts of 18:1 and 18:2 acids esterified as triacylglycerols compared to controls. The fatty acid distribution in the phospholipid fraction of thymuses was not altered by the appearance of leukemia.     

Possible case of rheumatoid arthritis from Sudanese Nubia

Due to its apparent absence in archaeologically derived skeletons, rheumatoid arthritis (RA) has generally been believed to be of fairly recent origin. A growing body of evidence now demonstrates that erosive lesions typical of RA are present in archaeological populations and that the antiquity of RA may be greater than previously expected. In support of this argument, a case of erosive arthritis is reported in a skeleton from Kulubnarti, Republic of the Sudan (c. 700-1450 A.D.). Lytic, erosive lesions and subchondral cysts are present bilaterally in the carpal and metacarpal joints of a female skeleton with an estimated age at death of 50+ years. These lesions are typical of those seen in clinically diagnosed rheumatoid patients. While their expression and distribution are highly suggestive of RA, interpretation must be made with due consideration for problems of differential diagnosis of this disease in archaeological material.     

Immunologic comparison of the conformations of apolipoprotein B. Investigation of methodologies for the reconstitution of delipidated and denatured apolipoprotein B with nonionic surfactants

Immunologic probes have been used to examine the conformation of apolipoprotein B (apo-B) as it exists within native low density lipoprotein (LDL) after lipid displacement with Triton X-100 and after denaturation with guanidine hydrochloride organic solvent delipidation and reconstitution with Triton X-100. Antigenic expression was assayed in two systems: by using either Triton X-100 or bovine serum albumin to maintain protein solubility. Apo-B delipidated by lipid displacement using Triton X-100 was virtually identical to LDL-apo-B in both systems, as assayed by polyclonal antisera prepared in rabbits against either antigen. Thus the native antigenic sites are preserved, although the displacement of the lipid core of LDL drastically alters the physical properties of the particle. Apo-B delipidated by solvent extraction in guanidine was reconstituted with Triton X-100 by several methods, and the products were examined immunologically. One method yielded a product that resembled apo-B as delipidated with Triton X-100, although full reconstitution could not be achieved. Nevertheless, Triton promoted refolding of apo-B to reform partial native structure as judged immunologically. By using both physical and immunologic methods for assessing structure, it is clearly evident that the perceptions of the conformational states of reconstituted apo-B can be very different, and multiple criteria need to be used to assess lipoprotein reconstitution.