Ag Treatment Research Articles

Inhibition of inducible nitric oxide synthase during high dietary salt intake

Background: Previous studies indicate that nitric oxide (NO) is involved in the regulation of blood pressure (BP) and natriuresis in response to high sodium intake. We investigated the role of inducible NO synthase (iNOS) in response to an increased salt intake. Methods: Conscious, chronically catheterized rats were exposed to a high-salt (6%) diet for 14 days while receiving vehicle or aminoguanidine ([AG]; 250 mg/kg/24 h), which selectively inhibits iNOS. A group of rats on normal salt intake + AG were also studied. Results: Aminoguanidine had no impact on BP (120 ± 2 v 116 ± 1 mm Hg, control v day14) or 24-h urinary nitrite and nitrate excretion (U NOxV), in rats on normal salt but prevented lipopolysaccharide-induced hypotension. High salt alone had no impact on BP (120 ± 1 v 121 ± 1 mm Hg), whereas U NaV (1.3 ± 0.2 v 3.5 ± 0.6 μeq/min, P < .001) and U NOXV increased with high salt intake. The natriuretic response persisted (1.5 ± 0.2 v 4.3 ± 0.8 μeq/min, P < .005), but the increase in U NOXV was prevented with chronic AG although BP fell slightly (121 ± 1 v 115 ± 1 mm Hg, P < .05). There was no change in plasma volume with high salt, and 24-h U NaV increased appropriately in the presence of AG. The in vitro NOS activity was not increased in kidney homogenates by high salt diet, nor was it affected by chronic AG treatment. Conclusion: We conclude that NO from an iNOS source is not essential for the regulation of sodium excretion and BP in the presence of a high-salt diet in a normal rat.

Aminoguanidine and aortic wall mechanics, structure, and composition in aged rats.

With aging, the aortic wall becomes stiffer. This could be because of changes in wall stress or composition. We investigated whether a specific change in wall composition, ie, accumulation of advanced glycation end products (AGEs) on the extracellular matrix, is a major factor. We measured aortic mechanics, geometry, and composition in 3-, 10-, 15-, 20-, and 30-month-old inbred normotensive Wistar-Glaxo/Rijswick rats and in a group of 30-month-old rats treated from 20 months onward with aminoguanidine (AG, 42 mg/kg per day), an inhibitor of AGE formation. Thoracoabdominal aortic (pressure) pulse-wave velocity (PWV) increased progressively with age (44% from 3 to 30 months). This age-related increase in aortic PWV was not related to changes in wall stress. For all ages, central (and peripheral) aortic mean blood pressures were not statistically different. Dilatation occurred (18% increase in internal diameter from 3 to 30 months), but this was accompanied by outward hypertrophic remodeling, with an increase in the medial cross-sectional area of 95% and in the ratio of medial thickness to internal diameter of 29%. Wall stress decreased with age (-34%). There was an increase in the ratio of elastic modulus (calculated from the Moens-Korteweg equation) to wall stress (calculated from the Lamé equation, 117% from 3 to 30 months), suggesting that a change in the composition of the wall is responsible for the age-linked increase in wall stiffness. Dry weight decreased slightly but significantly (-14%) with age. Total protein, elastin, collagen, and nonscleroprotein protein [total-(elastin+collagen)] contents did not change with age, but calculated densities of all 4 were halved (as the medial cross-sectional area doubled). The elastin/collagen ratio was statistically similar at all ages. The only significant effect of AG treatment was a fall in PWV (-20%), leading to a fall in the elastic modulus/wall stress ratio (-27% at 10 months of AG treatment versus 30 months of no treatment). In conclusion, the age-related increase in aortic wall stiffness is prevented by 10 months of treatment with AG, which has no effect on wall stress or composition, suggesting that AG may improve aortic wall stiffness by lowering the degree of AGE-induced cross-linking of the extracellular matrix scleroproteins, such as collagen.

Induction of permanent mixed chimerism and skin allograft tolerance across fully MHC-mismatched barriers by the additional myelosuppressive treatments in mice primed with allogeneic spleen cells followed by cyclophosphamide.

A pure method of drug (cyclophosphamide plus busulfan)-induced skin allograft tolerance in mice that can regularly overcome fully H-2-mismatched barriers in mice has been established. The components of the method are i.v. administration of 1 x 108 allogeneic spleen cells on day 0, i.p. injection of 200 mg/kg CP and 25 mg/kg busulfan on day 2, and i.v. injection of T cell-depleted 1 x 107 bone marrow cells from the same donor on day 3. Recipient B10 (H-2b; IE-) mice prepared with this conditioning developed donor-specific tolerance, and long-lasting survival of skin allografts was shown in almost of the recipient mice. In the tolerant B10 mice prepared with new conditioning, stable multilineage mixed chimerism was observed permanently, and IE-reactive Vbeta11+ T cells were reduced in periphery as seen in untreated B10.D2 (H-2d; IE+) mice. The specific tolerant state was confirmed by the specific abrogation against donor Ag in the assays of CTL activity and MLR and donor-specific acceptance in the second skin grafting. These results demonstrated that the limitation of standard protocol of cyclophosphamide-induced tolerance, which have been reported by us since 1984, can be overcome by the additional treatments with the myelosuppressive drug busulfan, followed by 1 x 107 T cell-depleted bone marrow cells. To our knowledge, this is the first report to induce allograft tolerance with a short course of the Ag plus immunosuppressive drug treatment without any kind of mAbs (pure drug-induced tolerance).

A dichotomous role for nitric oxide in protection against blood stage malaria infection

Nitric oxide (NO) is cytotoxic and cytostatic to blood stage malaria parasites in vitro, but the precise mechanism(s) by which it mediates an effect in vivo is not known. In particular, whether or not control of acute parasitemia depends on the presence of NO is unclear. We have shown previously that blocking NO synthesis at the time of its induction may cause an increase in peak primary parasitemia during infection of mice with Plasmodium chabaudi, suggesting that NO may be parasiticidal in vivo. However, as recent data indicate that NO suppresses Th1 cell proliferation in vitro by downregulating IL-2 production, we have investigated whether this immunoregulatory function of NO affects its capacity for anti-malarial activity. Treatment of P. chabaudi-infected mice with the iNOS inhibitor aminoguanidine hemisulfate (AG) starting just prior to the peak of primary parasitemia caused a significant elevation and extension of the acute infection and led to a partial but significant abrogation of the suppression of spleen cell proliferation to both mitogen and specific antigen observed when NO synthesis was not blocked. In the absence of NO, levels of IL-2, but not of IFN-γ, TNF-α, or of any Th2-regulated cytokines examined, increased significantly. However, when AG treatment was brought forward to the early ascending phase of primary parasitemia, significantly increased levels of IFN-γ and TNF-α, as well as of IL-2, were observed over those for infected control mice similarly treated with phosphate-buffered saline. Moreover, despite the absence of NO, parasitemias of AG-treated mice were not significantly elevated. The effect of AG therefore appeared to be dependent upon the timing of its administration in vivo. We propose that during malaria infections, there is a dynamic balance between the regulatory and anti-parasitic roles of NO. While the immunosuppressive function of NO leads to a downregulation in vivo of production of IL-2, and indirectly of IFN-γ and TNF-α, this perceived weakening of the host cell-mediated immune response is in part masked by the protective anti-malarial effects of NO itself.

In vivo blockage of nitric oxide with aminoguanidine inhibits immunosuppression induced by an attenuated strain of Salmonella typhimurium, potentiates Salmonella infection, and inhibits macrophage and polymorphonuclear leukocyte influx into the spleen.

Our laboratory has previously shown that after immunization with a strain of Salmonella typhimurium, SL3235, made avirulent by a blockage in the pathway of aromatic synthesis, murine splenocytes were profoundly suppressed in their capacity to mount an in vitro antibody plaque-forming cell (PFC) response to sheep erythrocytes. Evidence indicated that suppression was mediated by nitric oxide (NO), since the in vitro addition of NG-monomethyl-L-arginine blocked suppression. The present studies examined the effect of blocking NO production on Salmonella-induced immunosuppression by in vivo administration of aminoguanidine hemisulfate (AG). AG was administered to C3HeB/FeJ mice in their drinking water (2.5% solution) for 7 days prior to intraperitoneal inoculation with SL3235. AG treatment inhibited the increase in nitrate and nitrite levels in plasma and nitrite levels in the spleen seen in immunized mice. Importantly, AG treatment completely blocked suppression of the splenic PFC response and markedly attenuated the suppression of the response to concanavalin A in immunized mice, providing further evidence that Salmonella-induced immunosuppression is mediated by NO. AG treatment also alleviated the majority of the splenomegaly associated with SL3235 inoculation, which correlated with a blockage of influx of neutrophils and macrophages into spleens, as assessed by flow cytometry. AG treatment unexpectedly resulted in 90% mortality in mice injected with the highly attenuated vaccine strain of Salmonella, SL3235. Increased mortality in AG-treated mice correlated with inability to clear organisms from the spleen by day 15 postinoculation and with persistent bacteremia, compared with control mice. Collectively, these in vivo results underscore the dual biological consequences of NO production following Salmonella infection, with NO being necessary for host defense, but also having the potentially adverse effect of immunosuppression. A unifying hypothesis to explain how these seemingly paradoxical effects could both result from NO production is presented.

Effect of aminoguanidine on lipid peroxidation and activities of antioxidant enzymes in the diabetic kidney.

The aim of this study was to examine lipid peroxidation and activities of key antioxidant enzymes in kidneys of rats with streptozotocin (STZ)-induced diabetes and the effect of aminoguanidine on diabetes-induced alterations. Three groups, 6 rats each, were studied: control animals, not treated diabetic rats and rats treated with aminoguanidine (AG; 1 g/liter of drinking water). After 6 and 12 weeks the animals were sacrificed and lipid peroxidation products and activities of antioxidant enzymes were determined in their kidney homogenates. Malondialdehyde (MDA) content was significantly elevated and activities of SOD and catalase decreased in the kidneys of STZ-diabetic rats. AG treatment attenuated the increase in MDA content and diminutions of activities of SOD and catalase in the kidneys of diabetic rats. These results confirm oxidative stress in the kidney of rats with STZ diabetes and point to an antioxidant effect of AG in experimental diabetes.

Effect of aminoguanidine on plasma nitric oxide by-products and blood flow during chronic peritoneal sepsis.

We hypothesized that plasma nitric oxide (NO), generated via inducible NO synthase (iNOS) or endothelial constitutive NO synthase and measured via its by-products NO2- and NO3- (NO2- + NO3- = NOx) would increase and remain elevated during chronic peritoneal sepsis. We further hypothesized that treatment with aminoguanidine (AG; 50 mg/kg), a selective iNOS inhibitor, would decrease NO production and alter blood flow. Sprague Dawley rats were randomized to septic and nonseptic groups. Septic rats received an intraperitoneal cecal slurry (200 mg of cecal material/5 mL 5% dextrose-H2O/kg); control rats received sterile 5% dextrose-H2O (5 mL/kg) only. Plasma NOx and hemodynamics were measured 0, 4, 12, 24, and 48 h after sepsis or sham induction. We also examined the effect of AG, an iNOS inhibitor, on plasma NOx levels and tissue blood flow at 24 h. Septic rats uniformly displayed signs of sepsis, including lethargy, piloerection, and diarrhea. NOx levels were significantly elevated compared with controls at 4, 12, 24, and 48 h (p < or = .05). Septic rats also demonstrated hypotension (t = 12, 24, and 48 h) and tachycardia (t = 4, 12, 24, and 48 h). The infusion of AG (50 mg/kg intravenously for 30 min) at 24 h significantly decreased plasma NOx in septic animals. Plasma NOx concentrations returned to basal levels by 90 min after infusion of AG. In addition, blood flow studies demonstrated that AG treatment in nonseptic rats resulted in a significant decrease in blood flow to the stomach, skin, and adipose tissue, whereas AG infusion did not significantly alter the regional perfusion profile in septic animals. Furthermore, treatment with AG did not significantly alter mean arterial pressure in either group; however, nonseptic animals exhibited a decrease in stroke volume, and septic animals demonstrated an increase in heart rate. In contrast to the rise and fall of NOx levels in endotoxemia, this study demonstrates that the initial rise is sustained during 48 h of peritoneal sepsis. This sustained increase in NOx levels in this model correlated with the observable signs of systemic infection and may relate to enhanced iNOS activity. AG infusion demonstrated variable effects on regional tissue blood flow profiles in septic and nonseptic animals and attenuated the increase in plasma NOx levels in septic animals, an index of iNOS activity.

Solar Energy Conversion at the p ‐ InP / Vanadium3 + / 2 + Semiconductor/Electrolyte Contact: A Study Based on Differential Capacitance and Current‐Voltage Data

Previously unachieved values are obtained for the open‐circuit voltage (0.7 to 0.8 V) and the fill‐factor (76%) at the illuminated semiconductor/electrolyte contact (‘100’ face) coated with a submonolayer amount of silver. Photoelectrochemical solar cell efficiency is 11%, despite significant optical reflection and electrolyte absorption losses. Differential capacitance measurements demonstrate a semiconductor/surface energy barrier height of up to , independent of the Ag treatment. This value is considerably larger than typically found at solid‐state contacts. Barrier heights derived from Mott‐Schottky data are compared to photovoltages; results indicate that interface recombination and a slow charge‐transfer (bare ) and thermionic emission from the metal (Ag‐treated ) are important factors limiting the cell efficiency. Flatband potential shifts owing to a slow charge‐transfer under photocurrent flow are reduced by the Ag treatment. In a finite potential range of about 400 mV (0 to −400 mV/SCE), both photovoltages and Mott‐Schottky data reveal an unpinned Fermi level at bare and Ag‐treated electrodes. The unpinned barrier follows the ideal Schottky barrier model for an absolute SCE potential of −5.0 eV/SCE. Reference to related work at and is made.

Adrenal effects of low-dose aminoglutethimide when used alone in postmenopausal women with advanced breast cancer

Aminoglutethimide (Ag) is a potent aromatase-enzyme inhibitor used in the treatment of patients with breast cancer. In the past, it has been administered in doses of 1,000 mg/d (usually with 40 mg hydrocortisone). At these dose levels, the drug also affects multiple cytochrome P-450 enzymes, including enzymes for adrenal steroid biosynthesis. Recently, lower-dose regimens (500 mg/d) of Ag have been found to be just as effective for breast cancer therapy, but less toxic than the higher conventional dose. There is limited information on the adrenal effects at the lower dosages, and it is not known whether these effects are clinically significant. We measured basal and synthetic corticotropin (Cortrosyn)-stimulated levels of adrenal steroids in postmenopausal breast cancer patients before and during treatment with low-dose Ag (500 mg/d) administered without a glucocorticoid preparation. Basal levels of progesterone, 17-OH progesterone, and 11-deoxycortisol were higher after 2 months' treatment ( P < .01). After ACTH injection, peak levels of progesterone and 17-OH progesterone were higher ( P < .01), but in contrast, peak levels of 18-OH corticosterone were lower during treatment ( P < .02). Basal and peak levels of cortisol, aldosterone, and all other adrenal steroids were unchanged during treatment. We conclude that low-dose Ag treatment leads to partial inhibition of the 21-hydroxylase, 11-hydroxylase, and 18-hydroxylase adrenal enzymes. Since cortisol and aldosterone secretion remained normal with minimal shunting to or accumulation of adrenal androgen compounds, we believe that the mild inhibition was compensated for by further endogenous ACTH stimulation.

Neonatal Testicular Suppression with a GnRH Agonist in Rhesus Monkeys: Effects on Adult Endocrine Function and Behavior

Male rhesus monkeys secrete adult levels of androgen for 3 months postnatally. The role of this neonatal testicular secretion in sexual development was investigated by suppressing luteinizing hormone (LH) and testosterone (T) in neonatal male rhesus ( n = 6)by administering a gonadotropin-releasing hormone agonist (Ag) for the first 4 months of postnatal life. Controls ( n = 4) received vehicle. Six years later, endocrine function and sexual behavior were examined with ovariectomized females ( n = 6) receiving periodic estradiol (E2) treatment during the breeding and nonbreeding seasons. During the breeding season, there were no differences between Ag-treated and control males in levels of LH and T or in frequency of copulatory behavior. However, Ag-treated males masturbated less frequently than controls when the females were not on E2. During the nonbreeding season, Ag-treated males had lower T levels than controls when the females were not receiving E2 and copulated less when the females received E2, even though T levels were comparable. During both E2 and non-E2 treatments, Ag-treated males secreted less T per unit of LH than controls. Neonatal Ag treatment had no effect on social rank. These data demonstrate that neonatal testicular suppression, or the Ag treatment itself, altered systems regulating sexual motivation and neuroendocrine control of these males and suggest that the early neonatal period in male rhesus monkeys is another point when the developing central nervous system is sensitive to the organizing actions of androgens.

Mutagenic activity of 3-azido-1,2-propanediol and sodium azide applied to sugar cane callus cells

Chlorophyll deficient plantlets were obtained after the treatment of sugar cane callus cells with 3-azido-l,2-propanediol (AG) and sodium azide with approximately the same frequency. Both mutagenic agents postponed the regeneration of plantlets from calli, the total number of regenerated plantlets following the AG treatment being, however, higher than after the sodium azide treatment and control.

Evidence that Tumour Necrosis Induced by Aminated β1‐3D Polyglucose is Mediated by a Concerted Action of Local and Systemic Cytokines

Aminated beta 1-3D polyglucose (AG) causes regression of Meth A sarcoma in syngeneic mice when injected systemically on day 7 after tumour inoculation. AG does not concentrate in the tumour, but distributes throughout the body. AG treatment causes release of large amounts of interleukin 1 (IL-1) both in vivo and in macrophage cultures in vitro. AG is a weak stimulus for tumour necrosis factor (TNF) release both in vitro and in vivo. However, tumour tissue and sera from untreated mice on days 3 and 7 after inoculation contain significant amounts of TNF, whereas tumour tissue and sera on day 14 contain insignificant amounts of TNF. This correlates exactly with the sensitivity to AG treatment. IL-1, and TNF when injected locally cause reduction in tumour blood circulation and also shrinkage of the tumour. All these facts taken together indicate that the tumour circulatory failure and necrosis induced by AG are mediated by local TNF-unrelated to the treatment--potentiated by systemic cytokines triggered by the AG.

Analytic Reviews : Organ Procurement and Brain Death in Trauma Patients

The success rates and effectiveness of transplantation programs continue to increase, as does the need for cadaveric organs. Increasing organ procurement is a worthwhile goal that can be fully justified on economic, humanistic, and ethical bases. Although a great deal of progress has been made in terms of public and political awareness of organ procurement problems, additional changes and further education will be necessary before the number of cadaveric organs that are needlessly wasted can be reduced. Management of patients with unsurvivable head in juries or patients who are candidates for organ donation is a complex task involving critical care management, the declaration of brain death, and the identification of, and request for, organ donation from next of kin. This process involves the coordinated efforts of neurosur geons, critical care specialists, social workers, and the transplant team coordinators in organ procurement pro grams. Patients are best managed in tertiary centers that have staffs with the expertise and interest in performing these tasks. The time to cardiac death in brain-dead pa tients is frequently short and is hastened by the develop ment of rapidly progressive derangements in gas ex change, fluid and electrolyte homeostasis, temperature regulation, coagulation, and cardiovascular function. Premature death under these circumstances continues to be a major reason for organ-procurement failure. Ag gressive monitoring and treatment of the multiple med ical problems encountered, however, may reduce the number of patients who die prematurely and thus in crease organ procurement rates.

Effect of a gonadotropin-releasing hormone agonist on luteinizing hormone and testosterone secretion and testicular histology in male rhesus monkeys.

Three adult male rhesus monkeys were treated for 20 weeks with a gonadotropin-releasing hormone (GnRH) agonist (Ag; Wy-40972; Wyeth Laboratories, Philadelphia, PA) using osmotic minipumps. Ag administration resulted in a transient increase and then a precipitous decrease in the concentration of luteinizing hormone (LH) and testosterone (T). After 5 weeks, serum levels of LH were undetectable (less than 0.2 microgram/ml), while serum T was always detectable, but continued to fall throughout the period of Ag administration. The serum LH and T response to 50 micrograms of GnRH was abolished by 4 weeks of Ag treatment, and this effect persisted through the treatment period. Testicular histology at 20 weeks of Ag treatment exhibited diffuse atrophy of seminiferous tubules, suppressed germinal cell division, and the absence of spermatids or spermatozoa. There was no evidence of testicular necrosis or calcification of the seminiferous tubules. Following the termination of Ag infusion, serum LH and T concentrations rebounded to levels that exceeded pretreatment values for a 5-week period before falling back to baseline levels. A complete restoration of spermatogenesis and testicular volume occurred by 12 weeks after treatment. These data suggest that continuous Ag administration is an effective method of reversibly disrupting spermatogenesis in the male rhesus monkey.

Blockade of neonatal activation of the pituitary-testicular axis with continuous administration of a gonadotropin-releasing hormone agonist in male rhesus monkeys.

The objective of this study was to determine the effects of continuous GnRH agonist (Ag) treatment on neonatal activation of the pituitary-testicular axis in male rhesus monkeys. Five infants were treated continuously with Ag(10 micrograms/day; Wy-40972) for 112 days using osmotic minipumps beginning at 10-13 days of age. Two of five age-matched control animals were implanted sc with Silastic implants of comparable size to the minipumps; three did not receive sham implants. Ag treatment caused a fall in serum LH (bioassay) values to undetectable levels (much less than 0.1 micrograms/ml) within 3 weeks, where they remained throughout Ag treatment. Mean serum testosterone (T) levels fell from pretreatment values of 1.52 +/- 0.45 to 0.38 +/- 0.09 (+/- SE) ng/ml after 3 weeks of Ag treatment. The level of T never exceeded 0.60 ng/ml throughout the subsequent course of Ag treatment. In contrast, serum LH and T were elevated to levels that approached adult values during the first 2 postnatal months in control infants with or without sham implants. Both LH and T then gradually declined, and by 4 months of age, T levels were indistinguishable from those in Ag-treated animals. Control infants had an increase in serum LH from 0.56 +/- 0.10 to 2.67 +/- 0.49 micrograms/ml within 60 min of administration of 5 micrograms GnRH/kg BW at 60 days of age. Serum T values rose from 2.35 +/- 1.00 to 9.48 +/- 3.15 ng/ml during the same period. Seven weeks of Ag treatment abolished the LH and T responses to GnRH. Thirty days after the termination of Ag treatment (approximately 150 days of age), Ag-treated and control infants had comparable serum LH and T responses to GnRH, although the responses were reduced relative to the responses in controls at 60 days of age. These results suggest that continuous administration of Ag desensitizes the pituitary of the male infant rhesus monkey to GnRH and blocks neonatal activation of the pituitary-testicular axis.

Influence of continuous gonadotropin-releasing hormone (GnRH) agonist treatment on luteinizing hormone and testosterone secretion, the response to GnRH, and the testicular response to human chorionic gonadotropin in male rhesus monkeys.

Five adult male rhesus monkeys were continuously infused for 56 days with 25 micrograms/day of GnRH agonist (Wy-40972; Ag) using an implanted osmotic pump. Bioassayable serum levels of LH were elevated 8-fold on the second day of Ag treatment and then declined precipitously to below pretreatment levels by day 15. Serum levels of testosterone (T) changed similarly during Ag treatment, except that the fall in serum LH levels preceded the decline in serum levels of T by at least 2 days. Ag administration also eliminated the diurnal variation in serum LH and T. GnRH administration (50 micrograms) induced a 13- to 20-fold rise in serum LH and a 3- to 7-fold increase in serum T in control monkeys. After 4 weeks of Ag administration , none of the animals responded to GnRH. Both control and experimental monkeys had a rise in serum T in response to hCG after 7 weeks of Ag treatment. Basal levels of LH and T returned to normal by 12 days posttreatment, and the serum LH and T responses to GnRH were normal 19 days posttreatment. These results indicate that 1) continuous administration of Ag is an effective method of inducing antiferility effects in male rhesus monkeys; 2) pituitary desensitization is a major factor involved in Ag-induced gonadal dysfunction in this species; and 3) the method of administration may be the critical factor in determining the effectiveness of GnRH agonists.

Inhibition of human placental progesterone and estrogen synthesis in early human gestation by aminoglutethimide in vivo

The inhibitory effect of d,l-aminoglutethimide (AG) on the synthesis of progesterone and estradiol in early human pregnancy (8th–12th week of gestation) was investigated in volunteers; control group ( n = 11), AG group [1000 mg AG orally at test begin ( n = 6)]. Venous blood samples were taken at the beginning of the test and 0.5, 1, 2, 4, 8 and 24 h thereafter. In controls, no significant changes in serum progesterone and estradiol could be observed during 24 h. In the AG group, a decrease in progesterone and estradiol could be observed within 1 h after the test began; lowest serum steroid concentrations were reached after 4 h. Relative to the initial values taken as 100%, the greatest decrease in progesterone ranged between 37 and 83%, 62 15% ( x SD) ( n = 6); the greatest decrease in estradiol ranged between 32 and 78%, 51 17% ( x SD) ( n = 6). Twenty four hours after AG treatment, both steroids reached similar concentrations to those found at test begin. No clinical signs (e.g. uterine bleeding, contractions) for the abortifacient action of AG were observed. In conclusion, a single dose of AG (1000mg given orally) cannot induce a therapeutic abortion in early pregnancy. In accordance with in vitro studies, the inhibitory effect of AG on placental progesterone formation is due to an inhibition of mitochondrial cholesterol side chain cleavage. The decrease in estradiol is thought to be related to an inhibition of placental aromatase.

Nd:YAG Laser Photodisruptors

Commercial laser photocoagulators consist of: (1) a high power, short-pulse laser source, usually a Q-switched or mode-locked Nd:Y AG laser producing invisible nearinfrared radiation at 1064 nm; (2) an aiming/focusing laser system, using a continuous-wave He-Ne laser producing visible, red light at 632.8 nm; (3) a condensing lens that focuses the infrared treatment beam into a small focal spot at the working distance of the photodisruptor slit lamp; (4) an attachment system that connects the laser sources to the slit-lamp microscope to aim and focus the He-Ne laser (and thus the Nd:Y AG treatment beam) on target tissues. Basic principles, design, safety, and applications of photodisruptors are described elsewhere. I,2 In general, commercial photodisruptors may be differentiated on the basis of their: (1) pulse lengths, (2) aiming/focusing systems, and (3) attachment systems. 1 (1) Q-switched lasers produce single pulses or bursts of 1 to 9 pulses, each pulse of which is between 2 and 14 ns (l ns = 10-9 sec), depending on the commercial photodisruptor (Table 1). Mode-locked lasers produce a pulsetrain of seven to nine spikes over roughly a 30 ns interval. Each spike is 30 psec in duration (l ps = 10-12 sec). (2) With a single-beam focusing system, the operator moves the slit lamp forward and backward to minimize the size of a single red spot on the target tissue. With a doublebeam focusing system, the operator moves the slit lamp forward and backward until the two red spots fuse into

The reduction of Ag 2S and treatment of paper in a magnetron glow discharge

Ag 2S on silver antiquities can be reduced to metallic silver in hydrogen glow discharges but when heat-sensitive bases supporting corroded silver are exposed to such discharges there is risk of damage from bombardment of energetic electrons. The energetic electrons are secondary electrons released from the cathode by ion impact and accelerated in the adjacent positive ion sheath. Operation at large cathode work spacings or rough vacuum pressures (greater than 0.1 Torr) can reduce the electron energies by gas scattering but the work is then more remote from the active discharge region. Magnetron discharges using a closed magnetic tunnel field for electron entrapment do not cause electron heating and have been studied as a means of Ag 2S reduction. A high frequency (h.F.) crystal microbalance was used to follow the reaction process. Evaporated silver films deposited on the h.f. crystal were exposed to H 2S gas to form Ag 2S and the corroded layer was exposed to H 2 and Ar-H 2 discharges at a distance of 60 mm from an aluminium cathode with a tunnel magnetic field 52 mm in diameter. The frequency changes showed that Ag 2S films 400 Å thick could be reduced to metallic silver in 20 min at 10 −1 Torr in H 2 at an input of 250 V and 25 W. Reduction in an Ar-H 2 discharge ceased when only one half of the sulphide layer had been reduced. Experiments with gold-coated crystals showed that a sputtered film was deposited at the rate of about one monolayer per minute when argon was in the glow discharge. The sputtered layer was believed to be aluminium oxide which was impervious to atomic hydrogen. A low etching rate was observed when the sputter-coated crystal was exposed to a pure H 2 discharge. Ag 2S on evaporated silver films on paper could be exposed for reduction to the H 2 and Ar-H 2 magnetron discharges without apparent damage to the paper-cellulose base but uncoated paper became slightly discoloured, indicating that decomposition had occured. Uncoated paper was burnt rapidly in non-magnetron discharge in H 2 at 10 −1 Torr, 400 V and 25 W with a spacing of 60 mm. Less damage occured under the same conditions in non-magnetron Ar-H 2 discharges because the greater collision cross section of the argon atoms reduced the energy of the secondary electrons. It is believed that H 2 magnetron discharges could be used effectively for restoring corroded silver on cellulose supports using incontact masks to protect the uncoated base material from the discharge. Power input control would be necessary to avoid undue heating from hydrogen atom recombination and surface reactions.

Vitamin E and stress. 8. Nutritional effects of dietary stress with silver in vitamin E-deficient chicks and rats.

1. When chicks were given a fat-free casein–gelatin diet and, after 2 weeks of age, 0·15% silver acetate in the drinking water, they were found to have colourless exudates mainly in the pectoral region and partly in the peritoneal and pericardial spaces. Vitamin E and selenium, separately and together, failed to prevent this condition. Vitamin E was required together with methionine to prevent the condition. Methionine itself induced green staining of a few of the exudates.2. When lard was added to the casein–gelatin diet and the chicks were also given Ag, some green exudates were found in addition to the colourless ones. Addition of vitamin E or Se or both prevented the green exudates, but raised the incidence of colourless exudates. Methionine enhanced the green exudate condition, but again when combined with vitamin E prevented both types of exudate.3. A similar condition characterized by colourless exudates was induced by giving chicks diets based upon gelatin, yeast BPC, α-protein (with extra salts) or α-protein with gelatin. A torula yeast diet induced green exudates and haemorrhages.4. All the basal diets, which were deficient in sulphur amino acids, produced dystrophy of the breast muscle. Four of these diets contained no fat. Some diets also induced dystrophy of the gizzard. Vitamin E and Se protected against both these lesions. Methionine was protective in all except the torula yeast diet.5. Ethionine induced muscular dystrophy in chicks given a vitamin E-deficient diet adequate in sulphur amino acids. Additional methionine or vitamin E was protective, but cystine was not. Ethionine also produced a small incidence of green exudates and slight haemorrhages. This condition was prevented by vitamin E but not by methionine. The liver damage due to ethionine was not prevented by vitamin E, methionine or cystine.6. Liver necrosis was induced in rats by giving them an 8·3% casein diet and Ag, 130–1000 ppm, in the drinking water or the diet. Necrosis was produced even in the absence of dietary fat. Vitamin E and DPPD (N,N′-diphenyl-p-phenylenediamine) prevented necrosis, but adenine sulphate (0·25%), methionine (0·15%) and IONOX 330 (2,4,6-tri-(3′,5′-di-tert.-butyl-4′-hydroxybenzyl) mesitylene) did not. Se, 0·05 ppm, protected against 130 ppm Ag, but 1000 ppm Ag overcame the protective effect of 1 ppm Se. Similarly, 3 ppm cyanocobalamin was partly protective against 130 ppm Ag, but not against the higher concentration. Gold chloride (1000 ppm Au) had a mildly necrotic effect against which vitamin E did not protect. Neither copper sulphate (500 ppm Cu) not arsanilic acid (70 ppm As) induced liver necrosis.7. A high intake of Se (20 ppm as sodium selenate) was necrogenic in rats given a 10% casein diet; vitamin E and methionine did not protect. Vitamin E and cystine raised the low incidence of an exudative condition found in rats given 20 ppm Se. Methionine opposed this action of vitamin E.8. It was concluded that exudative diathesis in chicks could be resolved into a simple exudative condition and a superimposed haemorrhagic condition. Ag is a pro-exudative factor. Vitamin E and Se are also pro-exudative for chicks given the casein–gelatin–lard–Ag treatment. Torula yeast, methionine, lard, Ag (with lard) and ethionine are all pro-haemorrhagic factors. Se and Ag have an antagonistic relationship in rats and chicks; in chicks, however, Se synergizes with Ag when the supply of methionine is limited.