bluuebunny/crossref_metadata_2025_split huggingface dataset:
DESIGN OF EARLY CLINICAL TRIALS FOR NEW CONTRACEPTIVE METHODS
Authors: Mishell Daniel R. , Nash Harold A. 
Published: October 2009

ABSTRACT
A plan is outlined to shorten the current suggested duration of animal testing prior to clinical investigation with certain types of pharmaceutical agents. For many new drugs, especially steroids, after a pharmacologic profile is established, long term toxicity testing can usually be shortened prior to initiation of 6 months clinical trials involving about 1000 women. Clinical trials of this magnitude usually correlate very well with ultimate performance of contraceptive drugs, provided proper selection of subjects is performed with resultant good continuation rates. It is thus possible with certain new antifertility candidates to safely shorten the duration of both toxicological and clinical studies before initiating large scale field trials.
SPECIAL TOXICOLOGY FOR THE PROSTAGLANDINS
Authors: Kirton K. T. , Carlson R. G. 
Published: October 2009

ABSTRACT
The special requirements for toxicologic evaluation of the prostaglandins are considered. These compounds have many differences from the classical antifertility agents which seem to dictate special consideration for evaluation of safety and potential side effects. These include their ubiquitous distribution and spectra of pharmacologic activities, and extremely rapid in vivo metabolism to compounds of relatively low biological activity. All of these characteristics tend to cause prostaglandins to have a high order of acute activity, and therefore also acute toxicity. Most undesirable effects of steroids are seen only after prolonged administration. Toxicology and safety studies are designed to take these differences into account.
MACROPHAGE ACTIVATION INDUCED BY LYMPHOCYTE MEDIATORS
Authors: David John R. 
Published: October 2009

ABSTRACT
This paper is a brief review of studies which demonstrate that lymphocyte mediators can activate macrophages in vitro. Macrophages which have been incubated in lymphocyte mediator-rich Sephadex fractions show changed morphology, metabolism and function. These changes include an increase in adherence to glass, ruffled membrane movement, phagocytosis of some particles, glucose oxidation through the hexose monophosphate shunt and an increase in the activity of a membrane enzyme, adenylate cyclase. Such mediator-activated macrophages show enhanced bacteriostasis and tumoricidal activity. In addition, studies describing the role of membrane sugars and esterases in the interaction of migration inhibition factor and macrophages are reviewed.
ONTOGENY OF IMMUNITY IN MAN
Authors: Stites Daniel P. , Caldwell Joseph , Carr Martin C. , Fudenberg H. Hugh 
Published: October 2009

ABSTRACT
We have reviewed selected aspects of recent findings in the ontogeny of immunity in man. For obvious reasons, constraints placed on experimental work with human subjects, albeit deceased foetuses, limit the work to in vitro studies. Nevertheless, a number of novel and important concepts have emerged. First, as in lower animals, lymphoid development of the foetal thymus in general precedes the development of immunocompetence in peripheral lymphoid tissues. A striking exception to this rule is the finding of cells in early foetal liver which respond to allogeneic cells in the mixed lymphocyte culture some weeks before lymphoid organization of the thymus. In addition, the response of foetal cells to allogeneic cells in the mixed lymphocyte reaction (MLR) precedes the response to phytohaemagglutinin (PHA), a stimulant with relative T cell specificity. The use of markers for T cells to map the emergence of this class of lymphocytes correlates well with various functional attributes of T cells in in vitro culture systems. B cells emerge first in foetal liver at about 9 weeks' gestation, but formation of immunoglobulin by the foetus occurs at very low levels until after birth. There is a suggestion that progression from IgM to IgA synthesis occurs during human foetal lymphoid development. Taken as a whole, these data suggest a rather remarkable and perhaps unexpected degree of cellular and potential humoral immunocompetence at early stages of foetal development in man.
FERTILITY CONTROL THROUGH ACTIVE IMMUNIZATION USING PLACENTA PROTEINS
Authors: Stevens Vernon C. 
Published: October 2009

ABSTRACT
Numerous studies have demonstrated that antibodies to placental proteins in a variety of species are capable of preventing or disrupting gestation. Early work in this area was primarily directed towards the passive immunization of rodents with heterologous antisera to whole placental extracts. Toxicity and renal damage often accompanied fertility inhibition. More recent studies reported less toxicity and a higher specificity of antibodies to reproductive function when anti-placental antibodies were absorbed with serum and extracts of non-reproductive organs. Few studies have been reported in which active immunization with placental proteins was employed. The most detailed studies of active immunization have employed highly purified placental hormones. Immunizations of rats and rabbits with human placental lactogen have resulted in marked reduction in reproductive function. Immunization of human females with chemically altered (hapten-coupled) HCG resulted in the production of antibodies reacting with unaltered HCG and pituitary LH. These antibodies were capable of reducing the level of endogenous serum LH in pre- and postmenopausal women. They also altered the events of the menstrual cycle in premenopausal women. More specific inhibition of chorionic gonadotrophin has been obtained by immunization of baboons with the beta subunit of HCG. Antifertility effects without alterations in the menstrual cycle of female baboons immunized with the beta subunit of HCG have been reported. The antibodies produced in these animals reacted significantly with human LH in vitro. The possibility of using hormonal and non-hormonal placental proteins as antigens for the specific immunological inhibition of fertility remains.
CONCEPTS AND METHODS IN IMMUNOLOGY APPLICABLE TO THE CONTROL OF HUMAN FERTILITY
Authors: Celada Franco 
Published: October 2009

ABSTRACT
The reproductive event has been operationally subdivided into three periods, respectively including gametogenesis, fertilization and pregnancy: the feasibility of manipulating each period is discussed.
A note of caution arises from our present incomplete understanding of the nature of the materno-foetal immunological relationship, and from the danger of producing irreversible effects or of leading to autoimmunity.
II. MANIFESTATION OF THE ANTI-ANDROGENIC ACTION OF A STEROID ESTER TSAA-330 (16β-ETHYL-17β-HYDROXY-4-OESTREN-3-ONE CAPROATE) AND ELUCIDATION OF ITS LONG-LASTING MECHANISM USING A SIMPLE STEROID DETERMINATION TECHNIQUE
Authors: Masuoka Michio , Shikata Mutsushi , Fuziwara Reiko , Nakayama Ryo 
Published: October 2009

ABSTRACT
Using a simple steroid determination technique, in situ steroid absorption from a subcutaneously injected sesame oil solution in rats was pursued following the time-course changes in the steroid concentration. Based on the knowledge thus obtained, the antiandrogenic effect of a steroidal compound, TSAA-330*, could be manifested in the subcutaneous route.
(1) Anti-androgenic steroid TSAA-291* and its esters in the subcutaneously injected sesame oil solution were selectively absorbed into the general circulation at different rates according to their chemical nature and structures, while the oil itself remained at the injected site for a considerably long period. At the injected site where subcutaneous doses of steroids molar equivalent to 50 mg of TSAA-291 were administered in 5 ml/rat of sesame oil, TSAA-291 decreased to the level of 10% of the initial concentration on the 4th day. TSAA-328* decreased slowly to the 50% and 20% levels on the 7th and 21st day, respectively. TSAA-335* decreased more slowly to the 50% level on the 14th day. TSAA-330 decreased most slowly only to the 70% level on the 49th day.
(2) A single subcutaneous administration of 200 mg of TSAA-330 suppressed the weight increase of the accessory sex organs caused by a single subcutaneous injection of testosterone caproate (10 mg) in the immature orchiectomized rat. The suppressive effect was obvious from 2 weeks after the administration, and seemed to last for more than two weeks. The levator ani weight was not affected by the administration of TSAA-330. (3) Dose-dependent inhibitions of the accessory sex organs were obtained three weeks after a single subcutaneous administration of 50 to 400 mg of TSAA-330 in the adult male rat. (4) Daily oral administrations of 50 mg of TSAA-291 or TSAA-330 to the adult male rat for 8 days resulted in depression of the accessory sex organs to almost the same extent obtained with either agent. One week after the last administration, however, the weight of the accessory sex organs of the TSAA-291-administered animals recovered to almost the comparable level with the control, whereas a significant after-effect of the inhibition was still evident in the TSAA-330-administered animals.
IV. EFFECTS OF THE ANTI-ANDROGEN TSAA-291 (16β-ETHYL-17β-HYDROXY-4-OESTREN-3-ONE) ON THE SECRETION OF GONADOTROPHINS
Authors: Sudo Katsuichiro , Yamazaki Iwao , Masuoka Michio , Nakayama Ryo 
Published: October 2009

ABSTRACT
Effects of the anti-androgen TSAA-291 on the gonadotrophin secretion were studied.
(1) A single subcutaneous or oral administration of TSAA-291 and its caproate induced the ovulation in the proestrous rat of which the spontaneous ovulation was blocked by the treatment with chlorpromazine. (2) A single subcutaneous administration of TSAA-291 at 2.4 mg/kg to the adult male rat induced only a slight elevation in the serum LH and FSH levels at 30 min after the administration. Successive intramuscular administrations of TSAA-291 to the adult male rat for 2 or 4 weeks resulted in significant decreases in the serum LH and FSH levels at high dose levels. A dose-dependent decrease in the serum LH level but not FSH level was observed in the orchiectomized rat. (3) Successive intramuscular adminstrations of TSAA-291 at high dose levels to the male rat suppressed the plasma testosterone level in the testicular venous blood and general circulation.
Prevalence and incidence of diabetes in Norway
Authors: Midthjell Kristian 
Published: October 2009

ABSTRACT. There are limited data on the prevalence of Type 2 diabetes in Norway, since most studies conducted have not tried to separate between Type 1 and Type 2 diabetes. The prevalence of known diabetes in patients over 14 years was reported as 0.7 % in 1956. The present prevalence of known diabetes probably is about twice this percentage. This will be estimated in a planned study.
The treatment behaviour of Norwegian physicians has been analysed in a preliminary study. Based on this, 90 % of the patients at hospital outpatients clinics used insulin compared with only 16 % in general practice. The criteria applied for definition of diabetes varied considerably among the physicians, only 50 % of them using the WHO criteria. Age related prevalence data will be determined in a future screening project.
Key words: prevalence, incidence, Type 1 diabetes, Type 2 diabetes, treatment, Norway.
Natural history of non-insulin dependent diabetes mellitus
Authors: Beck-Nielsen Henning , Sørensen N. Schwartz 
Published: October 2009

ABSTRACT. The prevalence of NIDDM is about 1.5 %. Allready at birth the subjects developing NIDDM seem to be genetically primed. Environmental factors are able to precipitate the disease. Most subjects seem to run through a phase of IGT, before developing frank diabetes. The glucose homeostasis deteriorates with time resulting in complications, especially in the form of macrovascular diseases. The mortality from CHD is for NIDDM doubled compared with non-diabetics.
Diet treatment is of great importance for NIDDs but is not sufficient in all diabetics. Therefore, antidiabetic drugs, or in severe cases (secondary failures) insulin may be necessary. Insulin treatment seems to be preferable in diabetics not obtaining a near normal glucose homeostasis during diet and/or oral antidiabetic treatment as the mortality rate seems to increase in subjects with a poor glucose homeostasis.
Prevalence and incidence of type 2 diabetes in Finland
Authors: Reunanen Antti 
Published: October 2009

ABSTRACT. The prevalence and incidence of type 2 diabetes in Finland was evaluated on the basis of three large population surveys and the national register of diabetics receiving drug therapy. The prevalence of type 2 diabetes was 16 per 1000 in persons aged 30 years and over in a survey conducted in 1966–72,29 per 1000 in a survey conducted in 1976 and 32 in a survey from the years 1979–80. The secular increase in the prevalence rates seemed to be particularly evident in diabetics treated by diet only. According to the drug-recipient register the prevalence of type 2 diabetes is higher in eastern and northern parts of the country. The mean annual incidence of type 2 diabetes estimated on the basis of data from drugrecipient register and the latest of the three population surveys was in Finland in 1970s about 4 per 1000 in pesons aged 30 and over.
Key words: Diabetes mellitus, epidemiology
How to screen for diabetes mellitus
Authors: Bitzén Per-Olof , Melander Arne , Scherstén Bengt 
Published: October 2009

ABSTRACT. In an attempt to compare and evaluate different screening methods for diabetes mellitus in primary health care, urine and blood samples from 1082 consequtive patients were collected without any relation to meal or time of day. Urine glucose was determined by strip tests and quantitatively by the hexokinase method. Venous blood glucose was analysed by the hexokinase method and semiquantitatively by Dextrostix-Eyetone reflectance meter. 89 patients fulfilling the criteria for a positive screen were subjected to further diagnostic examination.
38 patients were classified as diabetics and 13 as having impaired glucose tolerance. In a control group randomly selected from negatively screened patients, all 30 patients had a normal glucose tolerance.
It was found that random blood glucose measurement using 7.0 mmol/l as screening level had significantly higher sensitivity than all other screening methods with comparable specificity.
Key words: Screening, diabetes mellitus, primary health care, methods, validity.
Insulin resistance in obesity, type II diabetes and stress
Authors: Smith Ulf 
Published: October 2009

ABSTRACT. Insulin resistance plays a major role for the reduced glucose tolerance in obesity, type II diabetes and stress. Both in vivo and in vitro studies strongly support the major importance of post-receptor perturbations as the cause of the insulin resistance in these conditions. One likely level for the post-receptor alterations is the reported reduction in glucose transport.
Key words: Insulin resistance, diabetes, obesity, insulin receptors, glucose transport.
Chlorpropamide-alcohol flushing and diabetes
Authors: Lyngsøe J. 
Published: October 2009

SUMMARY. Chlorpropamide alcohol flushing (CPAF) has been suggested as a genetic marker for a type of non-insulin dependent diabetes mellitus characterized by a strong genetic disposition and a low frequency of retinopathy. This theory has not been supported by later investigations.
Studies indicate that the most likely primary event in the CPAF phenomenon is an increased blood acetaldehyde level as a consequence of decreased acetaldehyde degradation. Probably the decreased elimination of acetaldehyde is elicited through an inhibitory effect of chlorpropamide on acetaldehyde dehydrogenase, the effect being most pronounced in subjects who have a genetically determined low activity of this enzyme.
Key words: Diabetes, chlorpropamide, ethanol, acetaldehyde.
Macroangiopathy in type II diabetes
Authors: Aro Antti 
Published: October 2009

ABSTRACT. Macroangiopathy is the most important cause of mortality and morbidity in type II diabetes. The atherosclerotic process in diabetes is similar to that found in non-diabetic subjects, but the laesions are more extensive and the clinical manifestations are more common in diabetic subjects than in the non-diabetic population. In diabetic patients from different populations, the prevalence of macroangiopathy is variable, and the relative frequency follows the pattern found in the respective non-diabetic populations. The relative risk of large vessel disease is in most populations higher for female than for male diabetics. Coronary heart disease is the most important manifestation of macroangiopathy while cerebrovascular disease and peripheral vascular disease are less frequent, although all these manifestations occur at increased frequency among middle-aged diabetic subjects. The incidence of peripheral vascular disease seems to increase with increasing duration of diabetes in middle-aged subjects, whereas coronary heart disease is particularly frequent in type II diabetes already at the time of the diagnosis.
Key words: atherosclerosis, complications, diabetes mellitus, macroangiopathy, mortality.
Clinical pharmacology of oral antidiabetic agents
Authors: Melander Arne , Wåhlin-Boll Elisabeth 
Published: October 2009

ABSTRACT. Currently available antidiabetic agents for oral intake are sulfonylureas (SU) and biguanides (BG). All SU seem to have the same mechanism(s) of action, including an enhanced release of pancreatic insulin, modulation of the release of other pancreatic hormones, and an enhanced peripheral sensitivity to insulin. Nevertheless, SU have different clinical effects, due to differences in intrinsic activity and pharmacokinetics. Thus, glipizide and glibenclamide are much more potent than tolbutamide and chlorpropamide, and should hence be preferred. Glipizide has the most rapid absorption and onset of action, and a shorter half-life and effect duration than glibenclamide, Accordingly, glibenclamide can exert a slightly better effect on fasting blood glucose but also involves a greater risk of long-lasting and sometimes fatal hypoglycemia. Thus, from the safety point of view, glipizide is to be preferred. Both glipizide and glibenclamide can be given once daily, and their efficacy may be improved if they are administered before, rather than together with, breakfast. The claim that SU enhance cardiovascular morbidity and mortality seems to be unfounded.
BG do not release insulin and do not provoke hypoglycemia but they may induce lactic acidosis, which is often fatal. This risk is most prominent with phenformin, partly beause this drug is eliminated by metabolic hydroxylation, which is greatly impaired in about 5 % in a Western population. In contrast, metformin is eliminated by renal excretion without preceding metabolic transformation; accordingly, the risk of lactic acidosis can be minimized if only metformin is used and is not given to subjects with impaired renal function. It remains to be established whether or not metformin can provoke permanent malabsorption of vitamin B12. From a theoretical point of view, the combination of SU and BG should be rational, but the clinical value of such combination therapy remains to be assessed.
Treatment failures: A common problem in the management of patients with type II diabetes
Authors: Groop Leif , Pelkonen Risto 
Published: October 2009

ABSTRACT. Secondary failure is a common problem in the treatment of patients with type II diabetes. The underlying mechanisms are reviewed, and special interest is focused on the assessment of insulin secretion and insulin sensitivity. Impaired beta-cell function seems to be the major cause of secondary drug failure in patients with normal weight, whereas insulin resistance is of greater importance in obese patients. The importance of Cpeptide determinations to detect patients needing insulin is emphasized. The concept of progressive deterioration of beta-cell function with time in type II diabetes is challenged.
Different treatment modalities for the management of patients with secondary drug failure are discussed and special interest is focused on the combination of insulin and sulfonylureas in the management of secondary failure patients with slightly impaired insulin secretion.
Key words: secondary drug failure, type II diabetes, Cpeptide, insulin sensitivity, oral antidiabetic drugs, insulin therapy.
The influence of strict control on diabetic complications
Authors: Hanssen Kristian F. , Dahl-Jørgensen Knut , Brinchmann-Hansen Olaf , _ _ 
Published: October 2009

Abstract. We studied 45 IDDM without c-peptide response, duration 7-22 years, without proliferative retinopathy. After 2 months run-in period, they were randomly assigned to: (P) 15 received CSII: (C) 15 received muliple s.c. injections via butterfly 5-6x daily;: (M) 15 received twice daily mixed rapid and long acting insulin.
All groups improved blood glucose control in the run-in period (p<0.0001). After change of treatment (P) and (M) improved further (p<0.01) but (C) was unchanged.
GFR was supranormal and decreased in (P) and (M). No regression of retinopathy was shown in any group. One in (P) had transient florid pre-proliferative retinopathy which regressed spontaneously without laser treatment.
We conclude that retinal response to strict control is complex. A transient deterioration may been seen.
Role of plasma C-peptide determination in the management of type II diabetes.
Authors: Aro Antti 
Published: October 2009

Abstract
The classification of diabetes may be sometimes difficult, particularly in persons with non-ketotic diabetes becoming manifest in middle age. The plasma C-peptide concentration, determined either in the fasting state or, preferably, after stimulation with iv. glucagon, gives a reliable estimate of the endogenous insulin secretion capacity of the individual. The C-peptide determination has improved the facilities for classification of diabetes and for appropriate choice of therapy. Patients showing stimulated plasma C-peptide values less than 0.6 nmol/l are definitely insulin-dependent, whereas values above the limit indicate that the patients can probably be managed without exogenous insulin (non-insulin-dependent diabetes). The C-peptide determination alone does not definitely indicate the therapy of choice. Conventional indicators of energy balance and glucose control together with regular follow-up of patients are still essential, particularly in the management of patients showing relatively low plasma C-peptide levels (between 0.6 and 1.1 nmol/l.). The stimulated plasma C-peptide concentration should be determined always before stopping insulin therapy in any diabetic patient or before instituting insulin therapy in a non-ketotic patient. In addition, plasma C-peptide determinations will certainly prove valuable in the classification of adult onset diabetic patients for the purposes of epidemiologic studies.
Treatment of non insulin-dependent diabetic women during pregnancy
Authors: Bompiani G. D. , Botta R. M. 
Published: October 2009

Abstract. From 1981 to 1984 90 cases of diabetic pregnancy were seen at the Palermo Center. Twentynine patients (32%) had prepregnancy type 2 diabetes, 20 (69%) of these were obese and were studied further.
The patients were divided into 2 groups of 13 and 7 patients. The first group was given a diet of 30 kcal/kg ideal prepregnancy weight. The second group was prescribed a low energy diet of on average 1200 kcal/day.
In the diet-restricted group, weight gain was less pronounced (7.9 ± 1.2 sd vs. 12.7 ± 8.6 kg), insulin requirement was lower (0.56 ± 0.22 vs. 1.00 ± 0.34 U/kg body weight) and the metabolic control was better than observed in the group given 30 kcal/kg body weight. The weight gain during pregnancy was proportional to the fetal weight index at birth (r = 0.72, P < 0.0005).
It is concluded that obese type 2 diabetic women are best treated by a low caloric diet and, when necessary, small doses of insulin. To establish the optimal caloric intake for obese pregnant type 2 diabetic women, the following formula is proposed: (30 kcal/kg prepregnancy ideal body weight/24 h) – X, where X is the % of prepregnancy obesity exceeding 120.