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The potential for pentachlorophenol (penta) to induce general and reproductive/developmental toxicity was evaluated in Crl Sprague-Dawley rats, employing a two-generation reproduction toxicity study. Penta was administered by gavage at doses of 0, 10, 30, and 60 mg/kg/day. In both generations, the parental animals (30/sex/group) were intubated daily for 10 weeks before cohabitation and continuing through cohabitation, gestation, and lactation periods. Intubation of the F1 generation was begun 28 days postpartum. Animals were evaluated daily for mortality and general toxicity (clinical observations, body weights and gains, feed consumption). Organ weights were recorded and histopathological evaluations were made. Specific indices of reproductive function evaluated included estrous cycles, mating and fertility, parturition, lactation, viability, and growth and development of offspring, including sexual maturation, sperm parameters, and numbers of ovarian primordial follicles. All deaths in the parental rats were unrelated to penta. Expected metabolic effects of penta, sporadic increased liver weights associated with hepatocellular centrilobular hypertrophy and vacuolation and lipofuscin pigmentation, were evident in the 10-, 30-, and 60-mg/kg/day dose group P1 and F1 animals. Toxicity, in the form of liver pathology (single cell necrosis), reduced body weights and associated reductions in organ weights, and reduced feed consumption were noted in both generations at the 30- and 60-mg/kg/day doses. Developmental toxicity associated with these doses included reduced pup weights and viability. The 60-mg/kg/day dose also resulted in delayed sexual maturation, decreased spermatid counts, small prostates and testes, decreased implantations, reduced fertility, and increased resorptions of embryos. Based on these results, it was concluded that 30 mg/kg/day is the lowest-observable-adverse-effect level (LOAEL) and 10 mg/kg/day is the no-observable-adverse-effect level (NOAEL) for both reproductive and general toxicity. These findings are consistent with results from previously conducted studies wherein reproductive/developmental toxicity was observed only at doses that also induced general toxicity. It differs from previous findings in that the NOAEL for general toxicity is two to three times higher for the more pure product than for products produced and tested previously. In addition, the results did not indicate bioaccumulation of penta. Thus, penta did not selectively affect reproduction or development of the offspring of rats at a dose of 10 mg/kg/day, a dose that is 7000 to 20,000 times higher than human exposure.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12171631&dopt=Abstract

Int J STD AIDS. 2002 Jul;13(7):449-52.
Bacterial vaginosis in climacteric and menopausal women.

Taylor-Robinson D, McCaffrey M, Pitkin J, Lamont RF.

Imperial College School of Medicine, St Mary's Hospital, Winston Churchill Wing, Paddington, London, UK.

The objective was to determine how frequently an abnormal vaginal flora occurred in women attending a menopause clinic and whether any abnormality might be related to a particular risk factor. Women completed a questionnaire on their gynaecological, sexual and medical history. Whether they were perimenopausal or postmenopausal was determined on the basis of symptomatology, duration of amenorrhoea and on a follicle-stimulating hormone (FSH) assay when clinically indicated. A speculum examination of the vagina was undertaken, at which time a smear of vaginal secretion was Gram stained and the bacterial flora graded as follows: grade 1, normal; grade 2, intermediate, and grade 3, bacterial vaginosis (BV). Of 100 women examined, 44 had grade 1 flora, 17 had grade 2 flora and 18 had BV. An apparent absence of, or very scanty, vaginal bacteria in which grading was not possible was found in 21 women. Women with BV had had more sexual partners than the others, but otherwise there were no discernible factors associated with the occurrence of BV. Women with vaginal atrophy were more likely to have an apparent absence of vaginal bacteria, but a few had BV.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12171662&dopt=Abstract

Gut. 2002 Sep;51(3):364-71.
B cell attracting chemokine 1 (CXCL13) and its receptor CXCR5 are expressed in normal and aberrant gut associated lymphoid tissue.

Carlsen HS, Baekkevold ES, Johansen FE, Haraldsen G, Brandtzaeg P.

Laboratory for Immunohistochemistry and Immunopathology, Institute of Pathology, and Department of Surgery, University of Oslo, Rikshospitalet, Oslo, Norway. hege.carlselinmed.uio.no

BACKGROUND AND AIMS: In mice, the B lymphocyte chemoattractant (BLC) CXC chemokine ligand 13 (CXCL13) is sufficient to induce a series of events leading to the formation of organised lymphoid tissue. Its receptor, CXCR5, is required for normal development of secondary lymphoid tissue. However, the human counterpart, B cell attracting chemokine 1 (BCA-1) has only been detected in the stomach and appendix and not in other parts of normal or diseased gut. Hence to elucidate the potential role of this chemokine and its receptor in human gut associated lymphoid tissue (GALT), we analysed their expression in normal intestine and ulcerative colitis (UC). METHODS: Frozen sections of surgical specimens were studied by multicolour immunofluorescence staining, in situ mRNA hybridisation, and reverse transcription-polymerase chain reaction. RESULTS: BCA-1 mRNA was detected in all normal colonic and UC specimens. BCA-1 was produced and accumulated in relation to peripheral dendritic elements of lymphoid follicles in Peyer's patches and normal colon, as well as in irregular lymphoid aggregates in UC lesions. BCA-1 was partially associated with the traditional follicular dendritic cell phenotype but also with extracellular fibrils in GALT structures. CXCR5 protein was expressed by mantle zone B cells and appeared at a high level on scattered germinal centre T cells. CONCLUSIONS: BCA-1 and CXCR5 are expressed in normal GALT structures as well as in irregular lymphoid aggregates in UC. This strongly suggests that BCA-1 plays an important role not only in the formation of normal GALT but also in the generation of aberrant lymphoid tissue in inflammatory bowel disease.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12171958&dopt=Abstract

Cell Tissue Res. 2002 Aug;309(2):313-22. Epub 2002 Jul 05.
Correlation between expression of selectins and migration of eosinophils into the bovine ovary during the periovulatory period.

Rohm F, Spanel-Borowski K, Eichler W, Aust G.

Institute of Anatomy, University of Leipzig, Liebigstr. 13, Leipzig 04103, Leipzig, Germany.

Leukocytes enter specific ovarian areas at a precisely defined moment, influencing cyclically changing structures such as follicles and corpora lutea. As yet, no studies have been published on the trafficking mechanisms involving the interaction between adhesion molecules on endothelial cells (ECs) and those on leukocytes. First, antibodies against human adhesion molecules were examined by flow cytometry with the aim of identifying the same bovine antigen. Western blot analysis and immunoprecipitation revealed that the molecules had the same molecular weight as their human counterparts. Afterwards, we investigated the distribution of these antigens in various ovarian stages using immunohistology. Among the molecules, P-selectin (CD62P) and L-selectin (CD62L) showed stage-dependent expression, and were thus examined further. In the preovulatory follicle, microvascular ECs were negative for CD62P. Few of the leukocytes expressed CD62L. In a freshly ruptured follicle, CD62P expression was found in the dilated vessels of the former thecal layer. Simultaneously, a large proportion of the rapidly increased numbers of leukocytes, mainly eosinophils, located around the microvessels of the outer thecal layer expressed CD62L. In the early corpus luteum development stage, CD62L showed peak expression with 70%-80% positive cells compared to leukocytes. In the secretory stage, the septal venules showed a consistent, but now weak, staining for CD62P. Few leukocytes expressed CD62L. During regression, the total number of leukocytes, now representing macrophages, increased significantly, but the proportion of CD62L-positive cells remained constant. In summary, we found a strong correlation of CD62P expression on activated ECs and the appearance of CD62L-positive leukocytes in the early corpus luteum development stage, suggesting the participation of both selectins in the migration of eosinophils under physiological conditions.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12172791&dopt=Abstract

Endocr Pract. 2002 Jul-Aug;8(4):292-5.
Cushing's disease after surgical resection and radiation therapy for nonfunctioning pituitary adenoma.

Kho SA, Nieman LK, Gelato MC.

Division of Endocrinology and Metabolism, SUNY School of Medicine, Stony Brook, New York, USA.

OBJECTIVE: To describe a patient with an aggressive nonfunctioning pituitary adenoma in whom Cushing's disease developed after two resections of tumor and radiation therapy. METHODS: We present a case report, with serial laboratory and immunohistochemical data, and summarize information about similar patients described in the medical literature. RESULTS: A 48-year-old woman had irregular menstrual periods, decreased peripheral vision, headaches, and weight gain. Laboratory and radiologic investigation revealed a large nonfunctioning pituitary adenoma. Transsphenoidal subtotal resection of the tumor improved her vision. Results of immunohistochemical studies were positive for b-follicle-stimulating hormone and b-luteinizing hormone. She had radiation therapy 1 year postoperatively for rapidly enlarging residual tumor. Bifrontal craniotomy was done 3 months later because of worsening vision. The pituitary adenoma from the second surgical procedure stained negatively for all pituitary hormones. Postoperatively, she received tapering doses of prednisone for 4 months. Two months after the last dose of prednisone, she had signs and symptoms of hypercortisolism. Inferior petrosal sinus venous sampling studies for plasma corticotropin confirmed the presence of Cushing's disease. She did not tolerate medical therapy. Bilateral adrenalectomy led to remission of hypercortisolism. CONCLUSION: Nonfunctioning pituitary tumors often come to clinical attention when they are large and cause symptoms associated with hypopituitarism or invasion of parasellar structures. In contrast, functioning pituitary tumors may have few compressive symptoms if they manifest with complaints attributable to excessive pituitary hormones.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12173916&dopt=Abstract

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