bluuebunny/crossref_metadata_2025_split huggingface dataset:
SPECIAL PROBLEMS IN TOXICITY TESTING OF LONG ACTING DEPOT CONTRACEPTIVES
Authors: Neumann F. , von Berswordt-Wallrabe R. , Elger W. , Gräf K.-J. , Hasan S. H. , Mehring M. , Nishino Y. , Steinbeck H. 
Published: October 2009

ABSTRACT
Two types of so-called "depot contraceptives", long-acting steroids which are of interest for human use, were studied in animals.
Norethisterone oenanthate, mainly gestagenic in the human and other species, turned out to be predominantly oestrogenic in rats. This oestrogenicity caused indirectly, via an enhanced hypophysial prolactin secretion, the well-known hypophysial and mammary tumours in rats.
Another synthetic gestagen, 4,6-dichloro- 17- acetoxy- 16α-methyl-4,6-pregnadiene-3,20-dione, which might be considered in its biological actions similar to preparations containing chlormadinone acetate or medroxy-progesterone acetate, induced no signs of oestrogenicity in dogs. It is surmised that its gestagenic influence indirectly, and probaby, via an enhanced hypophysial prolactin secretion caused "mammary nodules" in this "non-rodent" species. These studies have born out mainly two facts:
A synthetic steroid, norethisterone oenanthate, exerted different biological effects in different species: it was a gestagen in the rabbit, whereas in rats, its predominant influence was oestrogenic. The hypophysial prolactin secretion was enhanced in various species by different mechanisms: in rats, the oestrogenicity caused an increased prolactin plasma level, whereas in dogs, a gestagen with obviously no inherent oestrogenicity, 4,6-dichloro-17-acetoxy-16α-methyl-4,6-pregnadiene-3,20-dione, converted the histological appearance of the anterior pituitary into a condition with a greatly increased number of eosinophils. This histological finding was interpreted as an indicator for a hypersecretion of prolactin.
Hence, animal work with "gestagens" has only limited predictive value with respect to their possible effects in the human species. Therefore, inflexible recommendations are not helpful in solving the safety problem of long-acting steroids which affect primarily reproductive processes.
SPECIAL REQUIREMENTS FOR TESTING POST-COITAL CONTRACEPTIVES
Authors: Lerner Leonard J. 
Published: October 2009

ABSTRACT
Post-coital antifertility agents are a group of diverse chemical and pharmacological substances that have one activity in common, the prevention of or the termination of pregnancy. As with other classes of drugs, comprehensive toxicity evaluation must be performed in laboratory animals and in humans. Additional studies, however, should be undertaken to emphasize the influence of the clinical protocols on toxicity. Much toxicological information can be gained during broad-spectrum pharmacological testing and this information together with the biological activities can give direction for extended toxicity studies. Choice of animal species for these studies should be governed by parallelism with man phylogenetically, metabolically and physiologically, in response to hormones and drugs, in the metabolism and kinetics of compounds related to the drug in question, in specific areas related to reproduction and in other ways. It may take several different species to satisfy some of these requirements. The indicated use of the drug makes mandatory a study of foetal-toxicity and teratogenesis, and sub-antifertility doses as well as the recommended clinical dose should be employed in these studies. New types of drugs and new chemical entities require in-depth study, careful evaluation of effects, careful and constant clinical monitoring, and rapid dissemination of information about undesirable effects. While study of post-coital agents may not require great deviation from the manner in which other kinds of drugs are studied for toxicity, the fact that healthy women may be given such drugs for many years makes it imperative that all possible measures be taken to safeguard the health of these women.
SEX HORMONES – EFFECTS ON PROLACTIN CELLS IN THE RAT, DOG, MONKEY AND MAN
Authors: El Etreby M. F. , Günzel P. , Soulioti G. 
Published: October 2009

ABSTRACT
Histomorphological and immunocytochemical methods were used to study the effect of either physiological and pathological endogenous production or long-term exogenous application of high doses of sex (steroid) hormones on the prolactin cells in the anterior pituitary of experimental animals and man.
Using these methods it was shown that enhanced endogenous secretion of sex hormones, mainly of oestrogens, seems to produce nearly the same morphological changes in the anterior pituitary of the rat, dog and man. It was also possible to show that long term exogenous application of high doses of oestrogens or oestrogens and progestagens can stimulate prolactin cells in some experimental animals.
The demonstration of similar mechanisms in man calls for more extensive investigations on the possible role of the sex hormones on prolactin secretion.
CHARACTERIZATION OF SPERMATOZOAL AUTO-, ISO- AND ALLO-ANTIGENS
Authors: Voisin G. A. , Toullet F. , Almeida M. D' 
Published: October 2009

ABSTRACT
Three approaches are utilized to study and characterize spermatozoal antigens.
An immunological approach has demonstrated the presence of spermatozoal auto-, iso- and allo-antigens. Spermatozoal auto-antigens studied by several authors are able to induce the whole spectrum of immune reactions (delayed hypersensitivity, complement-fixing antibodies and anaphylactic antibodies) as well as of autoimmune aspermatogenic orchiepididymitis (AIAO). Different extraction procedures result in various preparations and even in different independent autoantigens (at least four), one protein, one membrane-linked antigen and at least two glycoproteins. Spermatozoal iso-antigens stricto sensu are determined by the Y chromosome and are present on at least 50 % of the spermatozoa. Spermatozoal allo-antigens are also present at the surface of spermatozoa, especially blood group antigens (ABO and MNS systems), transplantation antigens (HL-A, H-2) and also some other unidentified ones.
A biochemical approach has mainly been directed towards spermatozoal enzymes that have been shown to be antigenic even in the species of origin. This is the case for lactic dehydrogenase LDH-X (a mid-piece enzyme) and for acrosomal enzymes, e. g., hyaluronidase, possibly sorbitol dehydrogenase and trypsin-like acrosomal proteinase (the auto- and allo-antigenicity of the latter having not been established). At least three of these enzymes are known or supposed to play a role in the process of fertilization.
A clinical approach has described the presence of spermatozoal-coating antigen(s), such as transferrin or blood group substances from secretors obtained following the admixture of the secretions of the seminal vesicles. Indications were also obtained for the existence of antibodies directed against defined antigens. Several types of localization of antibodies on spermatozoa were described: acrosome (front part), equatorial segment, post-nuclear region, mid-piece and tail. Attempts at fractionation of human spermatozoal antigens are still at a preliminary stage.
Whatever the approach, the main interest of these antigens is that they are able to induce, in the species of origin or in a related species, antibodies capable of interfering with the normal process of reproduction, especially fertilization. In view of possible applications in the male or in the female, a few immunological considerations are of primary importance, particularly the localization of antigens (and their accessibility at the spermatozoal surface), their biological necessity for the reproductive process, the passage of the immune agents from the intravascular compartment to the genital tract, the possibility of inducing local immunization as well as to be able to direct the immune reaction at will toward the formation of immune agents responsible for the rejection reaction (sensitized cells, complement-fixing antibodies and complement) or the facilitation reaction (facilitating antibodies or suppressive cells).
IMMUNOLOGICAL INTERFERENCE WITH FERTILIZATION
Authors: Shivers C. Alex 
Published: October 2009

ABSTRACT
Rabbit antisera against mouse and hamster ovaries and sheep antisera against rabbit ovary have been used to demonstrate ovary specific antigens in these three species of mammals. That one or more of the specific antigens are located in the zona pellucida which surrounds the egg was indicated in immunofluorescence studies and by the effects antibodies have on the zona. After exposure to the antibody a precipitate forms on the zonae of preovulatory, unfertilized and fertilized eggs and all embryonic stages up to the time when the zona is shed. The precipitate was always seen near the outer surface of the zona suggesting that the active sites of the antigen(s) are located in this region. Trypsin and pronase which usually dissolve the zona were ineffective on the precipitated outer portion but did dissolve the inner, unprecipitated region. Species- and tissue-specificity and chemical nature of the zona are discussed.
Important roles for the zona antigen(s) in a number of early events in reproduction were indicated by the effects antizona antibodies have on fertilization and implantation. Pretreatment of unfertilized hamster eggs with zona precipitating antibodies was most effective in blocking sperm attachment to the zona. When the antibody was added subsequent to in vitro insemination, but before the sperm had passed through the outer region of the zona, sperm penetration was blocked. Mouse embryos treated with zona precipitating antibody and cultured in vitro failed to escape from the zonae, implying that implantation could be inhibited by antibody. Passive immunization of female mice with antizona antibodies and precipitattion of the zonae of hamster embryos in transfer experiments reduced the number of implantation sites. The identification of zona antigens and the effects of zona precipitating antibodies on early reproductive events encourage further studies on the zona in reference to immunological control of fertility.
TECHNIQUES FOR ELICITING MUCOSAL IMMUNE RESPONSE
Authors: Waldman R. H. , Ganguly R. 
Published: October 2009

ABSTRACT
Development of techniques for eliciting an immune response on mucosal surfaces is a relatively new area of clinical research. With the recognition of the existence of secretory immunity, independent of the systemic system, there was renewed interest in re-examining the conventional approach for optimal immunization techniques. A large body of data indicate that the majority of the secretory immunoglobulins and antibody produced to antigenic stimulation of mucosal surfaces is locally produced. Thus, antibody to C. albicans in the cervical or vaginal mucus has been shown to be of local origin and it predominantly belongs to the secretory IgA immunoglobulin class. The mechanism of antigen processing by the secretory surface leading to antibody formation remains a mystery, but it might be determined by the selective localization of antigens in the reticuloendothelial cells of the lamina propria, bronchi or small intestine. Usually application of antigen topically to the mucosal surface elicits local antibody formation to a greater extent than does parenteral immunization. On the other hand, a more pronounced systemic immune response is seen when the antigen is administered systemically. However, a number of other factors determine the quality and quantity of the immune response, e. g., the physical state of the antigen, live vs killed vaccine, dose, adjuvant, previous exposure to similar or cross-reacting antigens, and site of application of the antigen. These factors are discussed in the review. Recent observations suggest that cell mediated immunity is a component of the secretory immune system, and like the humoral mechanism, also may be partially compartmentalized.
SURFACE ANTIGENS OF NORMAL EARLY EMBRYOS AND A TUMOUR MODEL SYSTEM USEFUL FOR THEIR FURTHER STUDY
Authors: Edidin Michael , Gooding Linda R. , Johnson Martin 
Published: October 2009

ABSTRACT
We review experiments on the presence of strong transplantation antigens, H-2 antigens, in mouse gametes and early embryos. Parallels are drawn between antigenic structure of embryos and tumour cells, and experiments with a model tumour system, a teratoma, are presented indicating the presence in early embryos of surface antigens which are shared with the tumour.
I. ANTI-ANDROGENIC EFFECTS OF A NEW STEROID TSAA-291 (16β-ETHYL-17β-HYDROXY-4-OESTREN-3-ONE) AND ITS DERIVATIVES
Authors: Nakayama Ryo , Masuoka Michio , Masaki Tsuneo , Shimamoto Kiro 
Published: October 2009

ABSTRACT
Anti-androgenic properties of newly synthesized steroidal compounds, TSAA-291* and its derivatives, were studied in the rat.
(1) Subcutaneous administrations of TSAA-291 and TSAA-272* were effective in depressing the weight of seminal vesicles and ventral and dorsal prostates in the adult rat. (2) TSAA-291, TSAA-328* and TSAA-272 were shown to be anti-androgenic by the subcutaneous or oral route in the immature castrated male rat treated with testosterone propionate. The dose-response curves of all the test agents expressed in terms of percentage inhibition were approximately parallel to each other. Cyproterone acetate depressed the weight of levator ani muscle dose-dependently, whereas TSAA-291, TSAA-328 and TSAA-330* did not inhibit the muscle weight in a dose range sufficiently effective in inhibiting the weight of seminal vesicles and ventral and dorsal prostates. (3) TSAA-291 was also antiandrogenic against androstenedione and dehydroepiandrosterone.
(4) Local administration of the anti-androgenic compounds into the left seminal vesicle or left testis of the young adult rat depressed the weight of the seminal vesicle or testis on the treated side as compared with the vehicle-injected contra-lateral side.
III. HORMONAL SPECTRA OF ANTI-ANDROGEN TSAA-291 (16β-ETHYL-17β-HYDROXY-4-OESTREN-3-ONE) AND ITS DERIVATIVES
Authors: Masuoka Michio , Masaki Tsuneo , Yamazaki Iwao , Hori Tatsuhiko , Nakayama Ryo 
Published: October 2009

ABSTRACT
For the purpose of obtaining hormonal spectra of anti-androgen TSAA-291* and its derivatives, a variety of endocrine characteristics were studied.
(1) Androgenic and anabolic activity: Subcutaneous administration of anti-androgen TSAA-291 and its acetate, TSAA-328*, to the immature orchiectomized rat resulted in significant weight increase of the levator ani** but in only a nominal response of seminal vesicles and prostates even at a large daily dose of 9.6 mg. The resultant anabolic/androgenic ratio was estimated to be extremely high. (2) Oestrogenic activity: Uterine weight in response to these anti-androgens were sluggishly dose-dependent, and the maximal plateau response remained considerably lower than that induced by oestradiol-17β. The oestrogenic activity of these anti-androgens was estimated to be 1/200 000 or less as that of oestradiol-17β. A single subcutaneous dose of 100 mg of TSAA-291 or its caproate, TSAA-330*, did not induce the vaginal cornification in the adult ovariectomized rat. (3) Anti-oestrogenic activity: Antagonistic effect of these anti-androgenic compounds on the uterine weight response to oestradiol-17β was found in the immature ovariectomized rat. A single subcutaneous dose of 100 mg of TSAA-291 or TSAA-330 also induced the antagonism against the cornification caused by daily treatments with 1 μg oestrone in the adult ovariectomized rat. (4) Progestational activity: These anti-androgenic compounds proved to be less active than progesterone in the McPhail's test. (5) Anti-inflammatory activity: Daily subcutaneous dose of 20 mg of TSAA-291 for 6 days did not significantly depress the weight of granuloma developed around the cotton-pellet implanted in the young male rat. TSAA-291 did not affect the anti-inflammatory action of 1/6 mg of prednisolone phosphate. Combination of both agents seemed to be effective in enhancing the anti-androgenic action of TSAA-291, whereas prednisolone phosphate alone rather increased the weight of the accessory sex organs. (6) Liver glycogen deposition activity: Daily intramuscular doses up to 38.4 mg of TSAA-291 for 5 days did not increase the liver glycogen level in the adrenalectomized rat.
VII. ON THE MECHANISM OF ANTI-ANDROGENIC ACTION OF 16β-ETHYL-17β-HYDROXY-4-OESTREN-3-ONE (TSAA-291)
Authors: Nakayama Ryo , Masuoka Michio , Hiraga Kentaro , Miki Takuichi 
Published: October 2009

ABSTRACT
The mechanism of anti-androgenic action of a steroidal compound, TSAA-291, was summarized and discussed in reference to its drug-designing and structure-activity relationship. The target of the drug-design was to obtain a substance which is inactive in androgenic activity and is capable of antagonistically competing with androgen for the receptor. With this intention, the androgen molecule was rendered with a steric hindrance influencing upon the functional 17β-hydroxy group. Introduction of a bulky group at the steroidal position-13 or -16 led to anti-androgenic properties. Intense steric hindrance by introducing an enormously bulky group or complete elimination of the 17β-hydroxy group rather decreased the anti-androgenic activity. Of these anti-androgens thus synthesized, TSAA-291 proved to be the most active in the anti-androgen assay and also antagonistic against the uptake of [3H]testosterone by the rat ventral prostate.
Prevalence and Incidence of Type II Diabetes in Denmark Compared with Other Countries
Authors: Damsgaard Else Marie 
Published: October 2009

ABSTRACT. The prevalence of type II diabetes in Denmark increases with age to a maximum about the age of 70 years and the increase is higher for known diabetics than for previously undiagnosed diabetics. In the age group 60–74 years the total prevalence of diabetes was 6.1 % (5.5 % for women and 6.6 % for men).
The results of glucagon tests seem to indicate that about 60 % of insulin treated subjects after the age of 60 years are of type II. All diet treated diabetics and nearly all tablet treated and newly diagnosed diabetics are of type II.
The incidence of type II diabetes in Denmark has not been well described and might only be determined by reexamining the same fixed population with short intervals.
Differences in ascertainment, methods, and diagnostic criteria, from one study to another make a close comparison of different studies impossible.
Key words: prevalence, incidence, epidemiology, maturity onset diabetes.
Prevalence of type 2 Diabetes in Sweden
Authors: Sartor Gunnar 
Published: October 2009

ABSTRACT. Studies on the prevalence of diabetes mellitus, type 1 and type 2, in Sweden covering four decades give figures ranging from 0.35 % to 2.3 %. Figures are assumed to reflect type 2 diabetes in the majority of cases. In the most recent study the prevalence is 2.08 % for males and 1.95 % for females after standardization to total Swedish population. The disease becomes very common above the age of 60 (5.7 % or more). High risk groups suitable for screening are reviewed.
Key words:
diabetes mellitus, type 2
prevalence
risk group
screening procedure
A genetic marker for non-insulin-dependent diabetes and atherosclerosis
Authors: Owerbach D. , Johansen K. , Billesbølle P. , Poulsen S. , Schroll M. , Nerup J. 
Published: October 2009

ABSTRACT. The human insulin gene has been localized to the short arm of chromosome 11. The length of a segment of DNA associated with the human insulin gene is polymorphic. In patients with non-insulin-dependent diabetes mellitus (NIDDM) the proportion of subjects homozygous for DNA restriction fragments of a large size class (U alleles) in the polymorphic region was significantly higher than in normal controls. The U allele is thus associated with at least one type of NIDDM. The U-alleles were also strongly associated with macroangiopathy in diabetic as well as in non-diabetic subjects.
Key words: DNA polymorphism, chromosome 11, genetic marker, human insulin gene, non-insulin-dependent diabetes, glucose regulation, atherosclerosis, macroangiopathy.
Insulin secretion in type II diabetes
Authors: Faber Ole K. , Damsgaard Else Marie 
Published: October 2009

ABSTRACT: Beta-cell function was studied in young (20–30 years old, n=10) and old non-diabetic subjects (n=305), newly detected (n=87) as well as established (n=101) non-insulin dependent diabetic subjects, aged 60–75 years.
Fasting plasma insulin concentrations were 0.04 ± 0.01, 0.07 ± 0.04, 0.11 ± 0.07 and 0.11 ± 0.07 pmol/ml (mean ± sd) in the different groups. The corresponding C-peptide values were 0.36 ± 0.07, 0.63 ± 0.36, 0.98 ± 0.40 and 0.95 ± 0.45 pmol/ml, respectively. The relative changes in insulin and C-peptide concentrations were identical despite different kinetics of the metabolism of the peptides, indicating, that the elevated insulin levels of old as opposed to young non-diabetics and diabetic as opposed to non-diabetic subjects are caused by hypersecretion rather than decreased metabolic clearance of insulin.
Insulin Secretagogues. Possible Modulators of Glucose and Non-Glucose Stimuli
Authors: Lundquist Ingmar , Ahrén Bo , Scherstén Bengt 
Published: October 2009

ABSTRACT: A short overview is given concerning different insulin secretagogues and possible peptidergic modulators capable of acting on theβ-cell through the paracrine, the neurocrine or the gastro-intestinal endocrine pathway. Model experiments in animals have shown that peptidergic modulation of insulin secretion elicited by glucose stimulation, cholinergic stimulation or β-adrenergic stimulation seems to vary with the nature of the secretory stimulus. Several peptides influence only one type of secretory stimulus other may even display opposite effects with different stimuli. Generally, members of the secretin-glucagon family seem to be more insulinogenic than members of the gastrin-CCK family. Studies in man have shown that the insulin secretory defect in type II diabetes is mainly due to an abnormality of glucose recognition in the β-cell. Recent evidence seems to favour the idea that impairment of the complex system of non-glucose insulin secretagogues and modulators may be of additional importance in the heterogenous pathogenesis of type II diabetes. The sulfonylurea drugs may have beneficial effects not only on glucose-induced insulin release, but also on insulin secretion induced by nonglucose stimuli such as β-adrenergic stimulation which was found to be most sensitive to these drugs.
Key words: Insulin secretion, glucose and non-glucose stimuli, peptidergic modulation, type II diabetes, sulfonylurea.
Diabetes and arterial hypertension
Authors: Fagerberg Sven-Erik 
Published: October 2009

ABSTRACT. The epidemiology, pathogenesis, significance and management of hypertension i diabetic subjects are discussed. The frequency of hypertension in the diabetic population is about 20 %. Microangiopathy which leads to increased peripheral resistance and subsequently to impaired kidney function is probably the most important factor in the pathogenesis of hypertension in diabetes. All antihypertensive drugs have particular limitations in the diabetic patient. However the blood pressure must be treated more aggressively than in nondiabetics. Today we know that complications in well controlled diabetics occur later and to a lesser degree than in poorly controlled diabetics. Drugs that have an unfavourable effect on the metabolic processes in diabetes should, if possible, be avoided.
Key words: Hypertension, Type 1 diabetes, Type 2 diabetes, diabetic complications, nephropathy, retinopathy, obesity, antihypertensive drugs.