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Biomedical subjects

U Lang

Publications and source records attributed to U Lang.

At least 91 records · Page 5Linked to original sources

Diabetes mellitus in pregnancy. Management and outcome of diabetic pregnancies in the state of Hesse, F.R.G.; a five-year-survey.

From 1982 to 1986, data of 446 pregnancies in diabetic women were compared to equivalent information on 111,390 unselected non-diabetic pregnancies with the help of the Hessische Perinatalstudie (Hessian Perinatal Study, HEPS), a computerized system of collecting information on obstetrical care in the state of Hesse, F.R.G. Patient histories, pregnancy risks, birth risks, fetal outcome and maternal well-being were evaluated to survey the current situation of diabetic pregnancies in the specific constellation of widely decentralized obstetrical management and to point out possible benefits of stronger centralization of these high-risk pregnancies. Perinatal mortality in children of diabetic mothers (4.89%) remains substantially higher than in children of non-diabetic mothers (0.63%), with two thirds of the fetal loss occurring before birth. Infant morbidity, including macrosomia, shows the same impact of maternal diabetes. Maternal post-partum morbidity is increased in diabetic women. 37.9% of children of diabetic mothers were delivered in obstetrical units equipped for maximal care, 17.5% in primary care level hospitals. Perinatal mortality and morbidity as well as maternal complications indicate that diabetic women should receive obstetrical care in those centers that can provide all the necessary facilities.

Adult↗

Comparison of the effects of angiotensin II and vasopressin on cytosolic free calcium concentration, protein kinase C activity, and prostacyclin production in cultured rat aortic and mesenteric smooth muscle cells.

Differences in responsiveness of various vascular beds to pressor hormones have been reported. In our study, we have examined the effects of angiotensin II (Ang II) and vasopressin (AVP) on cytosolic free Ca2+ concentration [( Ca2+]c), protein kinase C (PKC) activity, and prostacyclin (PGI2) production in cultured aortic and mesenteric smooth muscle cells obtained from female Wistar rats. [Ca2+]c was determined using the Ca2+ fluorescent probe fura-2. PKC activity was assessed by the measurement of the phosphorylation of histone III-S, in the presence or absence of phospholipids, both in the cytosolic and particulate fractions. PGI2 production was estimated by a specific radioimmunoassay of its stable metabolite, 6-keto-PGF1 alpha. Our results demonstrate that basal production of PGI2 was higher in mesenteric than in aortic smooth muscle cells. In mesenteric cells, the [Ca2+]c, PKC activity, and PGI2 responses to AVP were higher than those induced by Ang II. This situation is the opposite of that observed in aortic smooth muscle cells. These results indicate different sensitivities to AVP and Ang II between vascular smooth muscle cells originating from two types of vessels.

Angiotensin II↗

[Acute dermal gangrene: a postoperative complication. With an example from obstetrics].

In the anglo-american literature the acute dermal gangrene is characterized as a cutaneous syndrome of infectious etiology which is usually leading--postoperatively or after an injury--to necrotizing destructions of the cutis, subcutis, subcutaneous fat, fascia or muscle. Depending on the localization of the involved tissue a superficial progressive bacterial gangrene is distinguished from a more deeply localized necrotizing fasciitis. Diagnostic and therapeutic considerations of these extremely rare syndromes are described in connection with an obstetric case which has been seen by us recently.

Abdominal Muscles↗

Delayed sexual maturation induced by daily melatonin administration eliminates the LH response to naloxone despite normal responsiveness to GnRH in juvenile male rats.

Daily administration of melatonin (MT) markedly delays sexual maturation in the male Wistar rat. In this study, we have evaluated pituitary responsiveness to GnRH and the level of tonic inhibition by endogenous opioids in normal juvenile male rats and in rats with delayed sexual development induced by daily afternoon MT injection (100 micrograms, s.c.) starting at 20 days of life. Plasma LH responses to repetitive intravenous GnRH administration (100 ng/100 g body weight), or to different doses of GnRH administered subcutaneously (5-100 ng/100 g body weight) were normal in MT-treated rats both at 30 and 40 days of life despite significantly lower number of pituitary GnRH receptors and decreased pituitary gonadotropin content. One naloxone (NAL) injection (2.5-5.0 mg/kg, s.c.) produced a significant increase of plasma LH in normal 40- and 55-day-old rats, which was not seen in MT-treated rats of the same age. In contrast, no increase of plasma LH was seen in 30-day-old control rats nor in MT-treated rats at this age. Pretreatment with morphine sulfate (10 mg/kg, s.c.), or with the potent Met-enkephalin analog FK 33-824 (1.0 mg/kg, s.c.) prevented the NAL-induced rise of plasma LH in control rats at day 40 of life. In all instances, plasma PRL levels were decreased after NAL both in untreated and in MT-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Fine structural studies of early mitotic stages in untreated and nocodazole-treated HeLa cells.

When cells in mitosis are treated with nocodazole, a microtubule-disrupting drug, it can be shown in comparison to untreated cells that microtubules are responsible for the polarized formation of indentations, folds, tubes, and crypts of the nuclear envelope in prophase nuclei. No translocation of chromosomes within the nucleus takes place. Microtubules are not necessary for chromosome condensation, nuclear envelope breakdown, the formation of trilaminar kinetochores, and the orientation of sister-kinetochores within one chromosome in relation to each other. The orientation of kinetochores in relation to the mitotic poles, however, is mediated by microtubules. The data shown here support the working hypothesis about chromosome translocation in prophase nuclei which was presented in an earlier paper.

Benzimidazoles↗

Angiotensin II but not potassium induces subcellular redistribution of protein kinase C in bovine adrenal glomerulosa cells.

The distribution of calcium-activated, phospholipid-dependent protein kinase (protein kinase C) between cytosol and membrane fractions was examined in bovine adrenal glomerulosa cells treated with angiotensin II or potassium. Protein kinase C was isolated from cytosol and from detergent-solubilized particulate fractions by DEAE-cellulose chromatography. A major peak of activity for both the soluble and particulate forms of adrenal glomerulosa protein kinase C was eluted at 0.05-0.09 M NaCl. The soluble and particulate forms were found to constitute about 95 and 5%, respectively, of the total enzyme activity in unstimulated cells. A second peak of kinase activity was eluted with 0.15-0.19 M NaCl, which was not dependent on the presence of phospholipids. Exposure of isolated cells for 20 min to 10(-8) M angiotensin II resulted in a decrease in cytosolic activity to 30-40% of control values, and in a corresponding increase in protein kinase C activity associated with the particulate fraction. This hormone-induced redistribution was found to be dose-dependent with an ED50 of 2 nM for angiotensin II, and it occurred rapidly, reaching a plateau within 5-10 min. It was prevented by the specific antagonist [Sar1,Ala8]angiotensin II. By contrast, stimulation with 12 mM KCl did not change the subcellular distribution of protein kinase C activity. These results suggest that redistribution of protein kinase C represents an early step in the post-receptor activation cascade following angiotensin II, but not potassium stimulation of adrenal glomerulosa cells.

Adrenal Glands↗

Identification of a major defect in insulin-resistant tissues of genetically obese (fa/fa) rats. Impaired protein kinase C.

In perfused lean rat hearts, the activator of protein kinase C phorbol myristate acetate (PMA), when present alone, stimulates glucose transport but inhibits the insulin stimulation of this transport. PMA also inactivates glycogen synthase in hepatocytes. In contrast, none of these effects are observed in hearts and hepatocytes of obese animals, indicating an impaired protein kinase C activation in these tissues, which are insulin resistant. Direct measurements of protein kinase C activity in lean rat hearts revealed that PMA provokes a translocation of the enzyme from a soluble to a particulate fraction. In obese rat hearts, the basal distribution of protein kinase C is altered (more activity is found in the soluble and less in the particulate fraction), and the translocation induced by PMA is impaired. Pretreatment of lean rats with PMA in vivo, aimed at downregulating protein kinase C, induces the same defects (i.e., insulin resistance and unresponsiveness to PMA) as those observed in hearts of untreated obese animals. The results indicate that part of the insulin resistance might be the consequence of altered modulation of insulin action by protein kinase C.

3-O-Methylglucose↗

Diuretic and hormonal responses to head-out water immersion in nephrotic syndrome.

The diuretic and natriuretic response to water immersion, which is known to increase effective central blood volume, was studied in eight edematous children with nephrotic syndrome. The rise in central blood volume was indicated by a decrease in hematocrit from preimmersion median of 40.2% to 38.6% during water immersion (P less than 0.05, Friedman test). Similarly, serum protein concentration fell from 36.7 gm/L to 33.5 gm/L (P less than 0.05). Water immersion induced diuresis from a preimmersion median of 0.33 ml/min/1.73 m2 to 1.52 ml/min/1.73 m2 (P less than 0.05). Osmolar clearance rose, as did sodium and potassium excretion. Urine osmolality fell during water immersion (P less than 0.05). Serum sodium concentration and plasma osmolality did not change. Plasma arginine vasopressin values fell from 11.1 pg/ml to 3.0 pg/ml (P less than 0.05), as did renin activity (8.5 ng to 5.2 ng angiotensin l/ml/hr, P less than 0.01), aldosterone (18.0 ng/dl to 10.1 ng/dl), and norepinephrine (344 pg/ml to 213 pg/ml, P less than 0.05). Water immersion produces a potent natriuretic and diuretic response in children with nephrotic syndrome.

Adolescent↗

Nocturnal urinary melatonin excretion and plasma cortisol levels in children and adolescents after a single oral dose of dexamethasone.

In the present study, the possible relationship between melatonin secretion as reflected by nocturnal melatonin excretion (2000 h-0800 h) and the pituitary-adrenocortical axis was investigated. Nocturnal urinary melatonin excretion and plasma cortisol levels were determined in 41 children with weight problems before and after a single oral dose of dexamethasone. A first group of 15 individuals with normal cortisol cycle (12.2 +/- 1.4 at 0800 h and 3.1 +/- 0.5 micrograms/100 ml at 1700 h), and levels below 1.0 microgram/100 ml after dexamethasone, showed a highly significant increase in melatonin excretion during the night following dexamethasone treatment (63.5 +/- 5.5 ng/12 h vs 33.6 +/- 3.0 for the control night, P less than 0.001). This increase was observed from prepuberty to young adulthood (pubertal stages PI-PV). In a second group of 16 subjects with mean cortisol levels similar at 0800 h and 1700 h (10.7 +/- 1.3 and 9.3 +/- 1.5 micrograms/100 ml respectively), but with a normal cortisol suppression after dexamethasone administration, nocturnal melatonin excretion increased from 21.2 +/- 2.1 to 33.4 +/- 3.0 ng/12 h (P less than 0.01). A significant increase was found in prepubertal children (PI) whereas no change was observed at the end of pubertal development (stages PIV-PV). A third group of 10 patients with both low amplitude cortisol cycles (16.2 +/- 2.5 and 10.8 +/- 2.4 micrograms/100 ml) and abnormal cortisol suppression after dexamethasone administration (9.1 +/- 2.4 micrograms/100 ml), showed no increase in melatonin excretion (24.2 +/- 2.7 and 24.9 +/- 3.7 ng/12 h).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Puberty in the rat: modulation by melatonin and light.

Although a role has been found for melatonin in species which have a seasonal reproductive cycle, very little is known on the role of melatonin in species such as the rat where seasonal cycles are a minor component of reproduction. But the rat is a photosensitive species, because it responds to changes in the lighting environment. Females do not become quiescent but they can have irregular estrous cycles, another way of controlling population dynamics. In this species, exogenous melatonin can exert an antigonadotropic action, providing conditions which apply to other species are also respected for the rat: melatonin must be given at the right time of the day, 9 to 12 hours after the onset of light, and at a given period of life, before the onset of puberty. Melatonin probably acts on the pattern of GnRH pulsatile secretion and the subsequent alterations of the hypothalamic-gonadal axis differ according to the sex of the animal. Endogenous melatonin rhythms are modified by the lighting environment, and results obtained with exogenous melatonin suggest that they could be one of the factors controlling timing of sexual maturation.

Animals↗

The pineal and pubertal development.

The pineal gland, through its major secretory product melatonin, influences seasonal breeding in species such as the hamster and the sheep. Recent studies from our laboratory have shown that melatonin also affects sexual development in the rat. A role for melatonin in humans has not yet been found. The laboratory rat is sensitive to daily administration of melatonin at the beginning of sexual maturation. The male rat is most sensitive between day 20 and day 30 of life. Melatonin does not permanently inhibit sexual maturation, since normal but delayed sexual development occurs after 45 days of life whether melatonin administration is discontinued or maintained indefinitely. In female rats, daily injection of melatonin during the prepubertal period delays the vaginal opening and disrupts the normal cyclicity of the first oestrous cycles. In both male and female rats, the inhibitory action of melatonin is highly dependent upon the time of injection, with maximal effects when melatonin is given in the late photoperiod. The inhibitory action of melatonin is most likely exerted at the hypothalamic level, possibly through interference with the control of pulsatile secretion of gonadotropin-releasing hormone. In contrast to some published work, our experiments provide no evidence for modifications of diurnal or nocturnal melatonin secretion during puberty in humans. Our results with the rat indicate that melatonin may be an important factor for the timing of sexual maturation.

Adolescent↗

Inhibitory action of exogenous melatonin, 5-methoxytryptamine, and 6-hydroxymelatonin on sexual maturation of male rats: activity of 5-methoxytryptamine might be due to its conversion to melatonin.

The effect on sexual maturation of 6 different pineal indoles, including melatonin, and of the metabolite 6-hydroxymelatonin was studied in the male rat after daily injections from 20 to 40 days of age. Only 5-methoxytryptamine (5MT) and 6-hydroxymelatonin (6M), in addition to melatonin, inhibited the neuroendocrine-reproductive axis during sexual maturation. Their potencies when injected in the afternoon were in the range of one-twentieth to one-fifth that of melatonin. Like melatonin these two indoles had no effect when injected in the morning. N-acetylserotonin, serotonin, 5-hydroxytryptophol and 5-methoxytryptophol did not influence sexual maturation either when injected in the morning or in the afternoon. Chromatographic separation was performed on plasma extracts from rats injected daily with the biologically active indoles and killed 10-120 min after the last injection. This procedure confirmed that 6M injections did not increase plasma melatonin levels. In contrast, plasma melatonin levels in 5MT-treated rats were increased 1 h after the 5MT injection. These results suggest that 5MT or part of it might be acetylated to melatonin; thus inhibition of sexual maturation might be mainly due to melatonin. These results indirectly support the contention that melatonin is the principal pineal indoleamine playing a role during sexual maturation.

5-Methoxytryptamine↗

Daily administration of melatonin delays rat vaginal opening and disrupts the first estrous cycles: evidence that these effects are synchronized by the onset of light.

The effect of daily melatonin administration was investigated in the immature female rat. Starting on day 15 of age, 100 micrograms melatonin were injected sc at different times of the day in animals housed in 12 h of light, 12 h of darkness or 16 h of light, 8 h of darkness. Melatonin given 9-11 h after the onset of light in both lighting regimens resulted in a 10-day delay of vaginal opening, a dissociation of the relation between vaginal opening and first proestrus, and a disruption of the initial estrous cycles. The same dose of melatonin given at other times during the photoperiod had no effect on sexual maturation. GnRH secretion in melatonin-treated animals was decreased, as judged by 30% lower pituitary GnRH receptor number in animals killed after opening of the vagina. During the diestrous phases, plasma levels of LH, FSH, and 17 beta-estradiol were similar to those in control rats, but during proestrus, the surge of FSH was higher, and the peak of estradiol was higher and of a longer duration. This hormonal pattern suggests a build-up of hormones in secreting cells, which follows the lower incidence of proestrous phases in melatonin-treated rats. This build-up of FSH was indeed present, with higher concentrations in the pituitary during diestrus after melatonin treatment, while pituitaries removed during proestrus had lower contents of FSH. These results confirm that chronic melatonin administration delays sexual maturation of female rat, probably by retarding maturation of hypothalamic GnRH-producing cells. Thus, melatonin could modify basal GnRH secretion or pulsatile release. Pituitary and ovarian responsiveness do not seem to be affected, since proestrous surges of 17 beta-estradiol, LH, and FSH occur, albeit at a reduced frequency. The results also show that there is a window of maximum sensitivity to administration of melatonin 9-11 h after the onset of light, and that this window of sensitivity is synchronized by the onset of light. This raises the possibility that the abnormal presence of endogenous melatonin during this period of the day could induce abnormal sexual development.

Animals↗

Barriers in cardiac substrate supply.

The capillary wall, due to its diffusional resistance, causes concentration differences between the vascular space and the interstitial space for substances which are released or taken up by the heart. Estimation of capillary transfer and interstitial concentration in isolated hearts, however, indicates a variable diffusional resistance, which in the case of glucose results from an insulin dependent transfer mechanism and in the case of lactate from a dependence of lactate transfer on lactate concentration or direction of transfer. Due to the unpredictable interstitial concentration investigation of sarcolemmal transfer appears to be possible at present only with isolated cardiac myocytes. Sarcolemmal transfer was studied for glucose and lactate. Recent investigations of lactate transfer revealed saturation kinetics, dependence on pyruvate (inhibition at low lactate concentration and enhancement at high lactate concentration) and dependence on pH (linear increase with lowered pH [8.0 to 6.7]).

Animals↗

Down-regulation and recycling of insulin receptors. Effect of monensin on IM-9 lymphocytes and U-937 monocyte-like cells.

Receptor down-regulation is the result of various cellular processes including receptor internalization, new synthesis, and recycling. Monensin, a monocarboxylic acid ionophore, has been used to characterize the role of recycling in the metabolism of insulin receptors on two cultured human cell lines, U-937 and IM-9, which have different rates of internalization. The U-937 monocyte-like cell internalizes insulin receptors readily. Incubation with monensin at low doses (10(-6) to 10(-7) M) for 2 h did not affect subsequent surface insulin binding. However, the drug markedly enhanced insulin-induced down-regulation. Monensin had little effect on ligand internalization in this cell line as demonstrated by quantitative morphometric analysis. The IM-9 lymphocyte, a slow internalizer, was less sensitive to monensin exposure. Prolonged exposure (12 h) to this compound of either cell line resulted in apparent inhibition of insertion into the surface membrane of both newly synthesized and recycled receptors. When solubilization was used to quantitate total cell receptors, there was essentially no difference in intact cell binding (i.e. surface receptors) and total cell binding in IM-9 cells when insulin-induced down regulation alone was compared to insulin and monensin. By contrast for the U-937 cells there was only a small further decrease in binding when monensin was added to insulin in the solubilized cells compared to the marked augmentation of down-regulation when monensin was added to insulin in intact cells. These data demonstrate that cells with a rapid internalization rate have an associated active recycling process. By contrast cells with a slow internalization rate have a similarly slow recycling rate. This is consistent with relatively equal rates of receptor biosynthesis and plasma membrane insertion in both cell types.

Cell Line↗