The influence of acupuncture stimulation on plasma levels of LH, FSH, progesterone and estradiol in normally ovulating women

Myelinated cultures of mouse spinal cord were exposed to sera obtained from rabbits affected by experimental allergic encephalomyelitis following challenge with whole white matter in complete Freund's adjuvant. In the presence of complement, the tissue response begins with an increased birefringence of its myelin sheaths. This is rapidly followed by a gamut of changes leading to demyelination. This study reports that, in the absence of complement, the response is arrested at the stage of increased birefringence. In this way, this early stage of the demyelinating process was available for detailed examination by light and electron microscopy. The brightened myelin sheaths appeared with a few hours of exposure and were seen around all axons and sometimes around cell bodies. This was often accompanied by abrupt breaks in the sheaths and angularly shaped myelin figures. Examination by electron microscope revealed a uniform increase in the myelin period from 11 nm. to 22 nm. The normally double intraperiod line was increased to four electron-dense leaflets, the additional two appearing to be derived from the close apposition of an additional electron-dense layer on the outer surface of the myelin sheath or oligodendrocytic membrane. Oligondendrocytes responsed with a prolific growth of processes whose membranes compacted to form swollen myelin. Neurons, astrocytes, and neuropil showed no changes. In its early stages, at least, the swelling was reversible. It would appear, therefore, that we have isolated the first stage of antiserum-induced demyelination in vitro, a stage which is now available for further study.     

Analysis of estrone, estradiol and estriol in serum and urine by mass fragmentography using GC-MS (author's transl)

The first successful analysis of estrogens in serum and urine was performed by mass fragmentography using a GC-MS combined system. The equipment used was Shimadzu LKB 9000 GC-MS (MID-PM). The TMSi derivative of the compounds were analyzed using the GC-MS system equipped with a 3 ft x 3mm column packed with 1.5% OV-1 and the temperature was programed from 200 degrees to 260 degrees C at 10 degrees C/min increments. The mass spectrum showed molecular ions at m/e 342, 416 and 504 which correspond to the TMSi derivatives of Estrone (E-1), Estradiol (E-2) and Estriol (E-3) respectively. Molecular ion peak of each compound was applied to establish the precise quantitative evaluation of E-1, E-2 and E-3. 1) The minimum detectable limits of the compounds injected into the column were ca. 2 pg for E-1, E-2 and 5 pg for E-3 respectively. 2) The sensitivity was of the order of ng or pg which enables quantitation with 2 ml of human serum and urine samples obtained from normally ovulating women. 3) This method was very convenient for extracting the compounds from biological fluids, and the procedure can be carried out easily in a short time. 4) Mass fragmentography makes possible the simultaneous measurements of E-1, E-2 and E-3 in samples obtained from pregnant women.     

Medroxyprogesterone acetate, estradiol, FSH and LH in peripheral blood after intramuscular administration of Depo-ProveraR to women

In this review article, the case in favour of the need for psychosexual counselling in family planning practice will be presented. Since psychosexual counselling is a multidisciplinary subject, family planning clinics and practices are ideally suited to the task. In presenting the case, liberal illustrative examples are provided in order to depict what the current and suggested extended facilities and techniques involve. The article is also intended to act as a comprehensive guide for students, nurses, medical practitioners and specialists alike, to bring them up to date in new concepts in history taking, physical examination and the sexually explicit aspects of family planning. Traditionally taught concepts may well be out of date in a modern society.     

Changes in the concentration of estrone, estradiol and estradiol in the blood of pregnant ewes

A chemical method was used for the study of the concentration of the three main groups of oestrogens in the blood of five ewes after mating in natural heat. The concentration values of all the three groups of oestrogens was found to increase in proportion with the length of gravidity. From the 30th to the 140th day of gravidity the average concentration values of oestrone increased from 309 to 1380 ng per 100 ml blood, those of oestradiol from 48 to 192 ng per 100 ml blood. Significant changes were recorded in oestrone between the 50th and 60th day and between the 130th and 140th day of gravidity; in oestradiol and oestriol such changes occurred on the 140th day of gravidity.     

Concentrations of estrone, estradiol, and estrone sulfate and evaluation of sulfatase and aromatase activities in pre- and postmenopausal breast cancer patients

This report concerns the evaluation of various estrogens, estrone (El), estradiol (E2), and estrone sulfate (E1S), as well as E1S-sulfatase and aromatase activities in pre- and postmenopausal women with breast cancer. The levels (in picomoles per g; mean +/- SEM) of the various estrogens in the breast tissue from premenopausal patients (n = 11) are: El, 1.4 +/- 0.5; E2, 1.2 +/- 0.6; and E1S, 1.2 +/- 0.3. In postmenopausal patients (n = 23), the values are, respectively, 1.0 +/- 0.4, 1.4 +/- 0.7, and 3.3 +/- 1.9. These concentrations of estrogens in the tumors of postmenopausal patients are significantly higher than those found in plasma. The activity of E1S-sulfatase in both pre- and postmenopausal patients was 50-200 times higher than that of aromatase. E1S-sulfatase and aromatase activities are significantly higher in post-menopausal than in cycling patients. It is concluded that despite the low levels of circulating estrogens in postmenopausal patients, the tissue concentrations of these steroids are several-fold higher than those in plasma, suggesting tumor accumulation of these estrogens. The physiopathology and clinical significance of these high levels of the various estrogens (E1, E2, and E1S) as well as sulfatase and aromatase activities in postmenopausal patients with breast cancer is yet to be explored.     

Expression of horse and donkey LH in COS-7 cells: evidence for low FSH activity in donkey LH compared with horse LH

Horse (Equus caballus) luteinizing hormone (eLH) and chorionic gonadotrophin (eCG), which have the same amino acid sequence, are unusual in that, although they express only LH activity in equids, they express dual LH and FSH activities in all other species tested. Donkey (Equus asinus) LH (dkLH) and CG (dkCG), which also share an identical peptide backbone, have been less well characterized and conflicting results concerning their FSH activity in heterologous species have appeared in the literature. In order to assess and compare the intrinsic LH and FSH activities of the horse and donkey LHs in heterologous species, recombinant eLH (r.eLH/CG) and recombinant dkLH (r.dkLH/CG) were expressed, for the first time, in COS-7 cells. Their LH activities were assessed in a rat Leydig cell bioassay, and their FSH activities were estimated in a bioassay using Y1 cells stably expressing the human FSH receptor. Human CG (hCG) was expressed (r.hCG) and analysed in the same system. The results showed that, whereas r.dkLH/CG was about twice as active as r.eLH/CG in the LH bioassay, it was five times less active than r.eLH/CG in the FSH bioassay; r.hCG was about three times less active than r.eLH/CG in the LH bioassay but was completely inactive in the FSH bioassay. These results confirm that dkLH/CG possesses significant FSH activity in heterologous species that is not attributable to contamination with FSH.     

Plasma concentrations of unconjugated estrone, estradiol-17beta and estriol, and HCS throughout pregnancy in diabetics and gestational diabetics

Plasma unconjugated estrone (E1), estradiol-17beta (E2) and estriol (E3), and HCS were measured in the same plasma samples collected throughout pregnancy in 19 gestational diabetics (GD) and 21 diabetics (D). When compared to the results obtained in 22 normal subjects, plasma levels of E1 and E2 were significantly elevated in D in the second half of gestation. The results were intermediate although closer to the normals, in GD. E3 values were not different from the normals in both D and GD. HCS values were lower than normal in early pregnancy in both D and GD. In late pregnancy HCS levels were not different from normal in either D or GD, although some individual values were much above the upper limit in some diabetic patients. The hormonal ratios in D and GD parallel those in normals, although E3/E2 and HCS/E2 were lower in D. These results are discussed with respect to the different behaviour of E2 and E3, taking into account the difference in their respective biosynthetic pathways. Besides a possible quantitative modification of the placental function in D, the results could tentatively be explained by a qualitative change in the fetal estrogen precursors to placental aromatization, in favour of the 16 non-hydroxylated compound. However, maternal modifications in precursor production or in estrogen metabolism can be an alternative hypothesis. Finally, the present work does not support the hypothetical estrogen deficiency in diabetic pregnancy. Estrogen treatment appears to have no objective justification.     

Sister chromatid exchanges and cell division delays induced by diethylstilbestrol, estradiol, and estriol in human lymphocytes

It had been found previously that exposure of human lymphocytes in vitro to diethylstilbestrol (DES), a synthetic estrogen and known human carcinogen, led to the induction of sister chromatid exchanges. More sister chromatid exchanges were induced in cells from pregnant women than from men. To see if the effects of DES could be induced by other estrogens, lymphocytes from a man and a pregnant woman were treated in vitro with the natural estrogens estradiol and estriol. These did not induce sister chromatid exchanges. To see if the presence of exogenous female hormones might be responsible for the increase in DES-induced sister chromatid exchanges seen in cells from pregnant women, lymphocytes from a man and a pregnant woman were also treated in vitro simultaneously with DES, estradiol, estriol, and progesterone. Treatments with these exogenous hormones did not alter the number of DES-induced sister chromatid exchanges. Our previous studies showed that DES also inhibits in vitro proliferation of lymphocytes. The results reported here show that estradiol also strongly inhibits this proliferation but that estriol is only a weak inhibitor. The cause of delayed cell proliferation induced by DES and estradiol was 2-fold: some of the cells were delayed in phytohemagglutinin-mediated blast cell transformation but, additionally, most cells had a prolonged cell cycle because of an extended G2 phase. These studies also showed that DES, but not estradiol or estriol, induced a low level of polyploidy in human lymphocytes.     

Immunohistochemical demonstration of FSH and LH in the pituitary of the developing frog, Rana esculenta

The analytical, intra-individual and inter-individual variations as well as the best storage conditions were determined for erythrocyte glutathione, and the reference values were established. A total of 396 apparently healthy people, 206 male, and 190 female, were randomly selected from villages and cities of the southern part of Turkey. The distribution was Gaussian and no significant difference was observed between the male and the female subjects. The mean (standard deviation) of the population investigated for glutathione was 6.9 (1.0) mumol/gHb. The analytical, intra-individual and inter-individual variations were assessed in 20 apparently healthy subjects and were found to be 4.63%, 13.67% and 11.16%, respectively. Whole blood stored at -70 degrees C for up to 10 days was shown to be the best storage condition for erythrocyte glutathione determination. The results of the index of individuality showed that glutathione reference values could be used for diagnostic purposes.     

Experimental studies on the positive feedback effect of progesterone, 17 alpha-hydroxyprogesterone and 20 alpha-dihydroprogesterone on the pituitary release of LH and FSH in the human female. The estrogen priming of the progesterone feedback on pituitary gonadotropins in the eugonadal woman

Administration of progesterone eugonadal women during the midfollicular phase of the menstrual cycle failed to induce a positive feedback effect on the serum concentrations of LH and FSH. The levels of estradiol in serum decreased following the injection of progesterone without a parallel change in LH and FSH concentrations indicating a direct ovarian effect of the exogenous progesterone. In the late follicular phase of the cycle, when preovulatory levels of estradiol were present in serum, or under a ethinyl estradiol treatment progesterone was able to induce an LH discharge indicating the requirement of an estradiol priming of the positive feedback of progesterone in eugonadal women. In order to establish the time required for a sufficient estrogen priming with preovulatory levels of estradiol in serum 3 mg of estradiol-benzoate were administered i.m. 1, 12 and 24 h prior to the administration of 30 mg of microcristalline progesterone in the midfollicular phase of the menstrual cycle, when progesterone alone did not cause an LH surge. Only when estradiol-benzoate was injected 24 h prior to the progesterone administration an LH surge reproducible in time course and magnitude occurred. Administration of estradiol-benzoate alone under these conditions did not cause an LH surge within the elapse of time after the injection when the progesterone induced LH surge occurred. Thus, these experiments demonstrate that a defined estrogen priming is required for the positive feedback effect of progesterone on the gonadotropin release in eugonadal women. Furthermore, progesterone levels in serum of about only 1--2 ng/ml were required for the induction of an LH surge indicating that under physiological conditions progesterone may have an supplementory effect on the primarily estradiol induced LH midcycle peak. 17-hydroxyprogesterone administered during the mid follicular phase of the menstrual cycle and under pretreatment with ethinyl estradiol failed to induce a positive feedback effect on the serum concentrations of LH and FSH, indicating that this steroid does not play a regulatory role on the midcycle LH release in women. 20alpha-dihydroprogesterone administered under the same experimental conditions as 17-hydroxyprogesterone seems to be able to induce an LH surge in serum provided there is an adequate estrogen priming.     

Chromogranin A: its clinical value as marker of neuroendocrine tumours

Pigmentation is a well recognised adverse effect of minocycline therapy. Various body sites, most notably the skin, nails, bones, thyroid, mouth and eyes are affected and the pigmentation may appear at multiple sites. In general, pigmentation results from long term administration of minocycline at cumulative doses greater than 100 g, although cutaneous or oral mucosal pigmentation may appear, regardless of dose or duration of therapy. When the skin is involved, the blue-black pigmentation develops most frequently on the shins, ankles and arms. Other patterns of skin involvement include pigmentation that is either generalised and symmetrical, or that develops at sites of inflammation. The bones of the oral cavity are probably the most frequently affected sites of pigmentation affecting greater than 20% of patients taking minocycline for more than 4 years. In contrast, the oral mucous membranes and teeth are infrequently pigmented from minocycline. Ocular, thyroid and visceral pigmentation is also relatively uncommon and usually develops only with high doses and long term minocycline use. Whereas pigmentation of the skin and oral mucosa is generally reversible when the drug is discontinued, the pigmentation is often permanent when other sites are involved. Although minocycline-induced pigmentation is not harmful, the drug should be discontinued when the adverse effect is recognised. All patients receiving minocycline, especially those treated for longer than 1 year, require screening for the development of pigmentation.     

Effect of a non-peptide NK-2 tachykinin receptor antagonist on LH, FSH, and prolactin release by rat hemipituitaries in vitro

Tachykinins are present in the anterior pituitary gland and there is evidence that they may have a direct intrapituitary role influencing the secretion of some of the hormones released by this gland. In this investigation, we have studied the effect of the non-peptide NK-2 receptor antagonist SR 48,968 (Sanofi Recherche) on the basal release of LH, FSH, and prolactin by rat hemipituitaries incubated in vitro, and also on the response to GnRH. SR 48,968 significantly inhibited prolactin release into the medium. The highest doses of this compound stimulated the basal release of LH by hemipituitaries from castrated, castrated testosterone-treated, and ovariectomized estradiol-treated rats, but not from intact male rats. SR 48,968 significantly inhibited the release of LH in response to GnRH. Since some tachykinin receptor antagonists have been demonstrated to act also on calcium channels, studies with verapamil, a calcium channel antagonist, were also carried out for comparison. Verapamil inhibited prolactin release into the medium and decreased the LH response to GnRH. These results suggest that tachykinins that bind NK-2 receptors, may have an intrapituitary role stimulating the release of prolactin, and that they may also modulate the response of the gonadotrophs to GnRH. The fact that verapamil shares some of the actions exerted by NK-2 receptor antagonists on the pituitary glandm however, suggests the possibility that some of the effects of NK-2 receptor antagonists may be mediated through calcium channel antagonism. Therefore, the results observed with the use of some of these antagonists should be interpreted with great caution.     

Computer-assisted intravenous anesthesia: value, method and use

To assess whether vomitoxin-induced dysregulation of IgA production and IgA nephropathy are reversible, relevant immunologic parameters were compared among experimental groups of B6C3F1 mice that were fed: (1) 25 ppm vomitoxin in AIN-76A semipurified diet for 24 weeks (treatment group), (2) 25 ppm vomitoxin for 8 weeks and then control diet for 16 weeks (withdrawal group), and (3) control diet for 24 weeks (control group). Levels of serum IgA and microhematuria index in the treatment group were elevated after 4 to 8 weeks and continued to increase with further vomitoxin exposure. IgA immune complexes and mesangial IgA deposition, as quantitated by interactive laser cytometer image analysis, were also increased with toxin exposure at Weeks 8, 16, and 24, whereas IgM, IgG, and complement component C3 deposition were unaffected or depressed. Serum IgA, microhematuria index, and mesangial IgA deposition in withdrawal mice remained elevated over those of the controls at Weeks 16 and 24 but were less than those of the treatment group. Cell recovery from Peyer's patches (PP) as well as the percentages of IgA+ and CD4+ cells in PP and spleen at Weeks 16 and 24 were greater in treatment mice than in controls, but only the percentage of IgA+ cells in PP was elevated in the withdrawal mice at these the same time points. When IgA secretion by unstimulated and LPS-stimulated splenic lymphocytes was used as the measure of systemic production, it was elevated in both treatment and withdrawal mice at Weeks 16 and 24. The results indicated that experimental dysregulation of IgA production and IgA nephropathy persisted up to 4 months after a discrete period of dietary vomitoxin exposure, but that the severity of these effects did not increase in a progressive fashion.     

Metoclopramide: a review of its pharmacological properties and clinical use

Metoclopramide, 4-amino-5-chloro-2-methoxy-N-(2-diethyl-aminoethyl) benzamide, is advocated for use in gastro-intestinal diagnostics, and in treating various types of vomiting and a variety of functional and organic gastro-intestinal disorders. Published data have indicated that metoclopramide assists radiological identification of lesions in the small intestine, facilitates duodenal intubation and small intestine biopsy, and eases emergency endoscopy in upper gastro-intestinal haemorrhage. Metoclopramide reduces post-operative vomiting and radiation sickness, and ameliorates some types of drug-induced vomiting. It may provide symptomatic relief in dyspepsia and possibly in vertigo, reflux oesophagitis and hiccups, but further controlled trials are needed to confirm the efficacy of metoclopramide in these proposed areas of use. It promotes gastric emptying prior to anaesthesia. Its effects in healing gastric ulcer and preventing relapse of duodenal ulcer remain unproven. Side-effects are few and transient, though alarming extrapyramidal reactions can occur in a small proportion of patients receiving therapeutic doses but more usually following excessive doses in young subjects. They respond rapidly to withdrawal of the drug.     

Immunohistochemical localization of estradiol and progesterone receptors in human uterus throughout pregnancy: expression in endometrial blood vessels

Although progesterone and estrogens are essential to maintain human pregnancy after implantation, the localization of their specific receptors in different uterine cell types during pregnancy has not been investigated. We studied uteri (n = 40) obtained during the first 3 months of pregnancy (n = 21) and in late pregnancy (n = 9) as well as from women 5-14 weeks pregnant (n = 10) who had received the antiprogestagen RU 38486 (Roussel-UCLAF) to induce cervical dilation. Frozen tissues were processed for indirect immunocytochemical staining with specific monoclonal antibodies against estrogen receptors (ER; Abbott Laboratories) and progesterone receptors (PR; Li 417). Specific staining for steroid receptors was only detected in the nucleus. In the endometrium, PR staining remained fairly constant throughout pregnancy, whereas ER staining was initially weak and then undetectable. PR was widely expressed in stromal cells and in spiral arterial wall cells, whereas ER was expressed in scattered stromal cells and arterial cells. Both PR and ER were absent from glandular epithelium, contrasting with the secretory activity during the first trimester. Spiral arteries of the endometrium and myometrial smooth muscle cells showed intense PR and moderate ER staining in early pregnancy. The progesterone antagonist RU 38486 (mifepristone), given in early pregnancy at a dose of 200 mg, caused a marked increase in ER staining and a smaller increase in PR staining in stromal cells, whereas the glandular epithelium remained negative for both ER and PR (except for one and two specimens, respectively). We conclude the following. 1) Stromal cells retain PR despite the high progesterone levels during pregnancy, in keeping with the role of progesterone in stromal decidualization. The absence of PR from the secretory glandular epithelium suggests a paracrine link between decidualized stromal cells and epithelial cells. 2) Significant PR down-regulation by progesterone during pregnancy occurs only in epithelial cells of the endometrium. 3) In contrast, the absence or low level of ER staining in the various cell types of the endometrium during gestation concurs with the known effect (down-regulation) of steroid hormones on ER mRNA or protein levels. The increase in ER in human decidua after RU 38486 treatment indicates that the main cause of the low ER levels is progesterone secretion. 4) The intense PR staining in smooth muscle cells of spiral arteries during early pregnancy suggests that progesterone is essential for modulating blood flow during pregnancy.