Sterility in women in sub-Saharan Africa

This article examines the problem of sterility in women in sub-Saharan Africa. The term sterility indicates a physiological inability to bear children: conception and early pregnancy may occur, but successful pregnancy does not. Primary infertility is the total absence of live-born children, whereas 2ndary infertility is the absence of additional children after a reasonably long period. Some naturally occurring level of primary infertility is expected in all populations of women, and various research had shown this to be 3%, on the basis of the proportion of women who have reached the end of their childbearing years childless. Although measurement of 2ndary fertility is more difficult, studies show that almost 3 times as many women suffer from 2ndary infertility as from primary infertility. Using the 3% standard of childlessness in women past childbearing, studies show that infertility varies by region in Africa, with higher levels of childlessness in Central Africa and parts of East Africa. Given the predominant natural fertility pattern of the region, the variation levels of infertility alone accounts for 60% of the variation in fertility levels. These high levels of infertility are acquired through infection, most particularly from sexual transmission of Neisseria gonorrhea and Chlamydia trachomatis. Recent findings reveal that more than 85% of infertile women have diagnosed reproductive pathology indicative of such genital infections. Together, gonorrhea and chlamydia challenge the medical resources of Africa, posing serious problems on the count of diagnosis, treatment, and their non-genital as well as 2ndary pathologies. Although the role of gonorrhea in infertility in Africa has long been recognized, the importance of C. trachomatis was not recognized until the early 1980s. The earlier absence of chlamydial control may account for the meager improvement in infertility by 1980, despite large scale penicillin campaigns. The resulting need for new and multivalent drug regimens and for good patient compliance (for chlamydia treatment) to make case-management feasible in the light of still severe constraints on diagnosis may well mean that notable improvements in infertility will still be hard to achieve for some time to come.     

[3H]-5-Methoxytryptoline is not actively accumulated by rabbit platelets

Summary 5-Methoxytryptoline (5-MeO-TLN, 6-methoxytetrahydro--carboline) inhibits with high affinity [³H]-imipramine binding to the serotonin transporter in platelets. To evaluate whether 5-MeO-TLN is a substrate for the serotonin transporter, the accumulation of [³H]-5-MeO-TLN into rabbit platelets was studied in vitro. At short incubation times (5 min), [³H]-5-MeO-TLN accumulation was temperature-sensitive, but not saturable over a concentration range from 0.06 mol/l to 10 mol/l Moreover, [³H]-5-MeO-TLN uptake was not affected by 100 mol/1 ouabain, its structural analogs tryptoline and 5-hydroxytryptoline, nor by the serotonin uptake inhibitors imipramine and citalopram. After longer incubation times (60 min), [³H]-5-MeO-TLN accumulation at O°C approached that seen at 37°C and temperature-sensitive [³H]-5-MeO-TLN uptake could no longer be observed. It is concluded that temperature-sensitive accumulation of [³H]-5-MeO-TLN is not mediated by the serotonin transporter and most likely represents a passive, diffusional process, the rate of which is temperature-dependent. The present studies thus confirm the hypothesis that 5-MeO-TLN affects [³H]-imipramine binding in platelets through a competitive mechanism and not via an allosteric interaction mediated through the substrate recognition site of the macromolecular complex of the serotonin transporter. Send offprint requests to S. Z. Langer at the above address     

Androstenedione may organize or activate sex-reversed traits in female spotted hyenas.

Spotted hyenas (Crocuta crocuta Erxleben) present a unique syndrome of reversal in behavioral and anatomical distinction between the sexes: females are heavier and more aggressive than males and dominant over them. The female's external genitalia include a false scrotum and a fully erectile pseudopenis through which mating and birth take place. Results of studies of circulating testosterone levels in wild spotted hyenas do not account for the "male-like" characteristics of the female. Androstenedione, however, is consistently higher in females than in males, particularly during early infancy. Experiments on rodents show that androstenedione can be a potent organizer of anatomical and behavioral differentiation. This study suggests that it may also produce the profound virilization of female spotted hyenas.     

T cell receptors. New knowledge of structure, genetic organisation, ontogenesis, and malignant transformation

T cell receptors which are members of the "immunoglobulin-superfamily" are capable of discriminating "self" from "non-self" and can be considered as analogues membrane-bound immunoglobulins. The minimal essential component, an alpha/beta glycoprotein heterodimer, is structurally similar to Fab1-fragments of immunoglobulins with constant and variable domains. Its genomic organisation strongly resembles that of antibodies. The alpha/beta-heterodimer is found to be associated with the CD3 complex of T lymphocyte membranes triggering cell activation. Another member of the T cell receptor family, the gamma-chain, is expressed during early stages of intrathymic differentiations. Cytotoxic and helper T cell lines contain gamma-chain-specific mRNA in much smaller amounts. It may be a reliable marker of T cell malignancies. The T alpha-gene family is also involved in the pathogenesis of T cell malignancies.     

In vitro effectiveness of dental floss in plaque removal

This study was designed to determine whether there was any measurable difference in the effectiveness of bacterial plaque removal between 4 commercially available dental flosses. By means of a highly standardized and controlled in vitro experimental model technique utilizing 50 freshly extracted third molars, the possibility of intra- and inter-individual variability was eliminated. Each tooth was individually mounted in a formatray block and the surface was finished to either a "planed" or "unplaned" surface configuration. The "planed" root surface (dentin) was achieved by using 600 grit wet-sandpaper for tooth surface reduction while the "unplaned" root surface was achieved by using 600 gift wet-sandpaper. The teeth were then individually processed to effect the growth of bacterial plaque (S. mutans) on the prepared surfaces. Each tooth was subsequently disclosed, flossed and photographed without interruption. The flossing was carried out on a flossing machine utilizing a controlled force of 50 g. A controlled direction of the stroke perpendicular to the long axis of the tooth, and a controlled frequency of flossing (2 strokes per trial) was used. The results of the clinical trials were evaluated utilizing Ektachrome slides of the previously flossed and disclosed tooth surfaces. The photographs were projected, measured, and statistically analyzed (Student t-test and paired t-test) for the effectiveness of plaque removal of the 4 dental flosses and the effect of root surface roughness on the ability of the flosses to remove bacterial plaque. It was found that on smooth, "planed" root surfaces, there were no measurable difference among the 4 flosses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Preliminary findings in the evaluation of hepatic malignancies by radioimmunodetection,X-ray computed tomography,and magnetic resonance imaging

In 12 consecutive patients with suspected metastatic carcinoma of the liver, we evaluated the sensitivity of radiolabeled antibodies to tumor antigens, magnetic resonance imaging, and X-ray computed tomography imaging in the detection of hepatic malignancies. Studies were performed with ¹³¹I labeled antibodies to CEA and/or CSAp; polyclonal, monoclonal and F(ab)₂ antibodies were used. Nontarget radioactivity was diminished by administration of ^99mTc reagents simulating nontumor distribution and use of a computer substraction method. In nine patients with confirmed liver neoplasms, radioimunodetection disclosed the foci of hepatic malignancies. In three patients with suspected liver neoplasms, the antibody studies were positive, but at this time have not been confirmed. X-ray computed tomography each disclosed mass lesions in five patients and magnetic resonance in three. These findings suggest that radioimmunodetection provides greater accuracy in the detection and localization of cancer than other diagnostic modalities currently used.This research was supported in part by NIH Grants CA37408, CA37409, CA37412, and CA39841     

Raising the ambient potassium ion concentration enhances carbachol stimulated phosphoinositide hydrolysis in rat brain hippocampal and cerebral cortical miniprisms

Summary The influence of the ambient potassium ion concentration ([K⁺]_ upon agonist stimulated hydrolysis of phosphoinositides (PI) has been studied in isolated miniprisms of rat hippocampus and cerebral cortex. When the external [K⁺] was raised from 6 to 18 mmol/l, there was little or no increase in the hydrolysis of PI in the absence of agonist, however, carbachol (100 mol/l) stimulated hydrolysis was greatly enhanced in both brain regions studied. Thus, carbachol stimulated the hydrolysis of PI to 146% and 386% of control levels at potassium concentrations of 5.8 and 18.2 mmol/l, respectively, in the rat hippocampus. A similar enhancement of muscarine (100 mol/l) stimulation was observed in cortical miniprisms with 18 mmol/l [K⁺]. A further enhancement was seen at higher ambient [K⁺], although basal hydrolysis of PI was then also increased. The carbachol-stimulated hydrolysis of PI found at both 6 and raised [K⁺] was prevented by atropine (1 and 10 mol/l) and tetraethylammonium (20 mmol/l), but not by 10 mmol/l Mg²⁺. Pirenzepine (50 nmol/l) also reduced this response. The ions Cs⁺ and Rb⁺ (but not Li⁺ or Tris⁺) produced a similar enhancement of the carbachol stimulation to that found with K⁺. At a buffer [K⁺] of 6 mmol/l, noradrenaline (100 mol/l) produced a 2-fold increase in the hydrolysis of PI whereas 5-hydroxytryptamine (100 mol/l) and histamine (500 mol/l) had little or no effect. However, histamine and 5-hydroxytryptamine did stimulate the hydrolysis of PI when [K⁺] was increased. Miniprism ATP content was not changed by a rise in [K⁺] to 18 mmol/l. The significance of these results is discussed in terms of the postsynaptic cellular events following cholinergic stimulation.     

Cervical tissue uptake of all-trans-retinoic acid delivered via a collagen sponge-cervical cap delivery device in patients with cervical dysplasia

The present study was undertaken to evaluate the systemic absorption and cervical tissue uptake of all-transretinoic acid (TRA), delivered via a collagen spongecervical cap delivery device in patients with intraepithelial cervical dysplasia. Ten patients with histologically proven mild or moderate cervical dysplasia were included in this pharmacologic study. The two TRA concentrations (0.05% and 0.372%) selected for study represent the starting and maximally tolerated doses used in phase I clinical trial. All-trans-retinoic-11-³H acid (³H-TRA, 500 Ci) was used to facilitate cervical tissue uptake studies. Cervical biopsies and post-treatment blood samples were obtained from each patient after TRA exposure. The uptake of TRA into cervical tissues four hours after drug administration was significantly increased at the maximally tolerated TRA dose. There was a rapid decrease in cervical tissue concentration of TRA at the 0.372% dose between 4 and 24 h after drug exposure, suggesting a relatively short elimination half-life of TRA in cervical tissues. HPLC analysis of post-treatment blood samples indicate that there was no systemic absorption of TRA after local cervical administration.     

Procarcinogen activation by rat and human mammary extracts

Sprague-Dawley rat mammary gland is extremely sensitive to tumorigenesisby single or multiple doses of several poly-cydk aromatic hydrocarbons.We obtained quantitative data on the in vitro mutagenic activationof several procarcinogens by 9000 g supernatant fraction (S9)from rat mammary gland using the Ames test. Mutagenic activationwas shown to be dependent on a nicotinamide adenine dinucleotidephosphate (NADPH) generating system. An S9 preparation frommammary tissue of lactating Sprague-Dawley rats was shown toactivate 2-aminoanthracene (2-AA). A polychlorinated biphenylmixture of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) givento rats greatly raised the specific activity (rever-tant TA98colonies/mg S9 protein) of the mammary tissue using 2-AA asa test carcinogen, and permitted detection of 2, 4-diaminoanisole(DAA) and 2, 7-diaminofluorene (DAF) activation. Procarcinogens2-aminofluorine (2-AF), benzo[a]-pyrene (BP) and aflatoxin (AFL)Bl were not detectably activated by mammary gland. Mutagenesisproduced in mammary S9 activation of 2-AA, DAA or DAF was significantlyinhibited by alpha-naphthoflavone (NF) but was inhibited minimallyby metyrapone (MP). Human mammary tumor cell lines (734B, SkBr3,MDA-MD-330) possessed inducible procarcinogen metabolizing activitiessimilar to those found in S9 of rat mammary tissue. We demonstrateda simple and convenient use of the Ames test to characterizeactivation of many potential mutagens and carcinogens for mammarygland. When a test compound such as 2-AA was used, selectiveenzyme induction and inhibition was demonstrated.