Studies on luteolysis: effect of antiserum to luteinizing hormone on sterols and steroid levels in pregnant hamsters.

The effect of luteinizing hormone antiserum (LH A/S) on sterol and steroid levels in luteal and non-luteal ovarian compartments, and on serum steroid levels of pregnant hamsters, was studied. Injection (ip) of 0.1 ml of LH A/S on day 7 caused termination of pregnancy and morphological regression of the corpus luteum (CL) within 18-20 h of treatment, whereas LH-free non-immune serum had no effect. Within 3 h of administration of LH A/S the luteal progesterone levels fell from a control value of 36.0 +/- 2.4 to 15.6 +/- 3.4 ng/mg, and estrogen from a control value of 20.8 +/- 3.4 to 12.2 +/- 1.5 pg/mg. By 12 h progesterone had dropped to 7.3 +/- 0.3 ng/mg whereas estrogen was undetectable by radioimmunoassay. Serum progesterone fell in 3 h from 5.53 +/- 0.39 to 3.15 +/- 0.26 ng/ml whereas estrogen fell from 172 +/- 26 to 123 +/- 9 pg/ml. The progesterone content of non-luteal ovarian tissue dropped in 3 h from 1.06 +/- 0.01 to 0.47 +/- 0.06 ng/mg and estrogen from 115.0 +/- 1.5 to 11.0 +/- 0.65 pg/mg. Both progesterone and estrogen were undetectable at 24 h. In the CL, free cholesterol concentration did not change significantly after A/S treatment, while esterified cholesterol increased from 2.82 +/- 0.14 to 4.14 +/- 0.25 mug/mg within 6 h and 5.52 +/- 0.17 mug/mg by 12 h. The results suggest that LH plays a critical role in the maintenance of CL of early pregnancy in the hamster and that deprivation of LH, even for periods as short as 3 h, significantly influences steroid production. The accumulation of cholesterol esters following LH-deprivation suggests that loss of cholesteryl esterase activity could be one of the events leading to luteolysis.     

Passive immunization with an antibody to the beta-subunit of ovine luteinizing hormone as a method of early abortion--a feasibility study in monkeys (Macaca radiata).

Antiserum to the beta-subunit of ovine luteinizing hormone (oLH-beta) raised in monkeys (Macaca radiata) has been tested by a variety of criteria both in vivo and in vitro to establish its ability to neutralize oLH, hLH, and human chorionic gonadotropin (hCG). Passive administration of this antiserum caused inhibition of ovulation and termination of pregnancy in recipient monkeys as indicated by premature vaginal bleeding and a significant reduction in serum progesterone and estrogen levels. The results suggest that antiserum raised in monkeys against oLH-beta can neutralize monkey LH as well as monkey CG.     

Hormonal control of uterine growth: alterations in luminal epithelial deoxyribonucleic acid synthesis after intraluminal application of estrogen

Administration of a single injection of estradiol (E2) causes a maximum increase in DNA synthesis in the uterine luminal epithelium approximately 24 h later. We previously reported that animals receiving a second injection of E2 15-18 h after the first show an apparent decrease in DNA synthesis measured in this cell type at 24 h. This apparent decrease in DNA synthesis is due to a shift in the time course of DNA synthesis rather than an absolute decrease in this parameter. In this report we demonstrate that this inhibitory effect of a second injection of E2 is also observed after intraluminal instillation of the hormone. This effect is dose dependent and appears to result from a shift in the time course of luminal epithelial DNA synthesis. The intraluminal instillation of E2 produces the same pattern of nuclear receptor localization as sc administration of the hormone. These results suggest that this inhibitory effect we previously described results primarily from a direct action of E2 on the luminal epithelium.     

Imidacloprid poisoning: a case report

Imidacloprid is a systemic, chloronicotinyl insecticide. It is generally considered nontoxic to humans based on available literature. Its effects are mediated through acetylcholine receptor blockade. We report a patient with such poisoning who had respiratory arrest, for which he had to be mechanically ventilated, and who subsequently recovered. This is only the second such case report.     

New butenolides from two marine streptomycetes

Chemical examination of two marine Streptomycetes has resulted in the isolation of four new butenolides, namely 4, 10-dihydroxy-10-methyl-dodec-2-en-1,4-olide (1), two diastereomeric 4,11-dihydroxy-10-methyl-dodec-2-en-1,4-olides (2/3), and 4-hydroxy-10-methyl-11-oxo-dodec-2-en-1,4-olide (4). The structures were identified by interpretation of the 2D NMR and mass spectral data.     

Evidence for triiodothyronine receptors in human endometrium and myometrium

Thyroid gland dysfunction in humans may cause various female reproductive tract disorders. Thyroid hormone action is thought to be mediated by high-affinity low-capacity receptor proteins located in the nucleus. The studies detailed in this report were undertaken to determine if uterine nuclei contain specific high-affinity receptors for thyroid hormone. Nuclei from human endometrium and myometrium were prepared by homogenization and centrifugation following routine surgical procedures. With the use of isolated nuclei, binding experiments with 125I-triiodothyronine (T3) revealed a dissociation constant of approximately 1 X 10(-9) M in both endometrium and myometrium with a maximum number of binding sites equivalent to 0.06 and 0.21 pmol/mg of DNA, respectively. The solubilized binding sites were destroyed largely by trypsin treatment. Competition experiments revealed the following relative binding affinities for these nuclear binding sites: L-T3 greater than D-T3 greater than L-thyronine greater than reverse T3. These results indicate the presence in the human uterus of specific high-affinity binding sites with characteristics expected of a T3 receptor and thus raise the possibility that thyroid hormone may exert effects on the uterus through these receptors.     

Stimulation of uterine deoxyribonucleic acid synthesis by 1,1,1-trichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl)ethane (o,p′-DDT)

The administration of 1,1,1-trichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl) ethane (o,p′-DDT) to immature female rats produced a maximum increase in uterine wet weight and DNA synthesis measured by tritiated thymidine incorporation into uterine DNA 24 hr after treatment. These responses were maximal at a dose of 250–1000 mg/kg of (o,p′-DDT); half-maximal responses occurred in the range of 10–40 mg/kg. These responses were specific for o,p′-DDT, since (o,p′-DDT)T was much less potent. 17β-Estradiol and (o,p′-DDT) also produced increases in total uterine DNA content and in total uterine protein content. The uterine responses to maximum doses of 17β-estradiol and (o,p′-DDT) were not additive, suggesting that both compounds interact with the same receptor. In a series of experiments, the administration of 250 mg/kg of (o,p′-DDT) produced increases in uterine weight that were the same as those seem after 17β-estradiol treatment, increases in DNA synthesis that were 60–80 per cent of those produced by 17β-estradiol and an increase in total uterine DNA that was 66 per cent of that observed after 17β-estradiol treatment. 17β-Estradiol and (o,p′-DDT) also produced significant increases in uterine wet weight and DNA synthesis in ovariectomized/adrenalectomized rats, indicating that the effects of the pesticide are not mediated via adrenal steroids.     

Coronary Artery Disease in Patients with Chronic Kidney Disease: A Clinical Update

Chronic kidney disease (CKD) is an independent risk factor for coronary artery disease (CAD). Coronary artery disease is the leading cause of morbidity and mortality in patients with CKD. The outcomes of CAD are poorer in patients with CKD. In addition to traditional risk factors, several uremia-related risk factors such as inflammation, oxidative stress, endothelial dysfunction, coronary artery calcification, hyperhomocysteinemia, and immunosuppressants have been associated with accelerated atherosclerosis. A number of uremia-related biomarkers are identified as predictors of cardiac outcomes in CKD patients. The symptoms of CAD may not be typical in patients with CKD. Both dobutamine stress echocardiography and radionuclide myocardial perfusion imaging have moderate sensitivity and specificity in detecting obstructive CAD in CKD patients. Invasive coronary angiography carries a risk of contrast nephropathy in patients with advanced CKD. It should be reserved for those patients with a high risk for CAD and those who would benefit from revascularization. Guideline-recommended therapies are, in general, underutilized in renal patients. Medical therapy should be considered the initial strategy for clinically stable CAD. The effects of statins in patients with advanced CKD have been neutral despite a lipid-lowering effect. Compared to non-CKD population, percutaneous coronary intervention (PCI) is associated with higher procedure complications, restenosis, and future cardiac events even in the drug-eluting stent era in patients with CKD. Compared with PCI, coronary artery bypass grafting (CABG) reduces repeat revascularizations but is associated with significant perioperative morbidity and mortality. Screening for CAD is an important part of preoperative evaluation for kidney transplant candidates.