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At least 19 recordsLinked to original sources

Preventing the heterosexual spread of AIDS: what is the best advice if compliance is taken into account?

It has been recently advocated that avoiding partners who may be at high risk of carrying HIV provides 5000-fold better protection against HIV infection than usage of condoms [1]. In this paper, it is demonstrated that this guideline is largely based on unrealistic assumptions. If the sensitivity of identifying high-risk partners, realistic estimates of the efficiency of mechanical and chemical barrier methods, and the compliance in following either strategy are taken into account, use of condoms and/or suppositories containing nonoxynol-9 might be more effective than the attempt to avoid high-risk partners. Thus, both barrier methods should be strongly recommended for casual sexual heterosexual contacts.

Acquired Immunodeficiency Syndrome↗

4-Isoxazolyl-1,4-dihydropyridines: biological, theoretical, and structural studies.

Biological activity was determined for a series of seven isoxazolyldihydropyridines (IDHPs). The highest biological activity was observed for 5-alkyl-3-phenyl-IDHP (1), for which the O-endo conformation at the ring juncture between the heterocyclic rings is known in the solid state. The 3,5-dialkyl-IDHPs were intermediate in overall activity. A theoretical study of rotation about this ring juncture was performed to estimate the relative energy and barrier to rotation for the different conformers as a function of both the ring juncture between the heterocyclic rings and the esters in the 3- and 5-position of the dihydropyridine. Molecular mechanics predicts the minimum energy conformer to be O-exo-ap,ap, while quantum mechanical calculations predict O-exo-sp,sp as the minimum-energy conformer. Both methods indicate that the barrier to rotation about the heterocyclic ring juncture should be relative low, but both methods appear to overestimate the difficulty of ester rotation. A single-crystal X-ray diffractometry study of the (3,5-dimethylisoxazolyl)dihydropyridine 2 was carried out, and shows the O-endo ring juncture and sp,sp ester conformation. 2D NOESY NMR spectroscopy indicates the presence of both conformations about the ring juncture, at room temperature, as evidenced by correlations for both alkyl groups on the isoxazole with the C-2 methyl on the DHP moiety. The ap ester conformer was also evidenced by NOESY, indicating that ester interconversion must take place.

Animals↗

Hydration of human stratum corneum studied in vivo by optothermal infrared spectrometry, electrical capacitance measurement, and evaporimetry.

Optothermal infrared spectrometry (OTIS) is a recently introduced method for specific measurement, in vivo, of water in the skin. In the present study the method proved well suited to register the increase in water content in stratum corneum following application of emollients. The results were compared with those obtained with a commercial instrument, the Corneometer, and the two methods were found to match very closely. Neither method indicated any difference in hydration of normal skin between young and elderly women. Evaporimetry was used to detect any influence on the water barrier function of the skin following application of emollients; even though the water content of the skin was significantly higher after emollient treatment, the transepidermal water loss remained unchanged.

Adolescent↗

Skin reactions to irritants assessed by non-invasive bioengineering methods.

Pathophysiological components of irritant contact dermatitis caused by 3 chemically-different irritants were investigated. 20 healthy volunteers were patch tested with sodium lauryl sulphate, nonanoic acid and hydrochloric acid on the flexor side of the upper arm. The skin response was evaluated after 24, 48 and 96 h by visual scoring and measured by the following bioengineering methods: transepidermal water loss measurement, electrical conductance for measurement of skin hydration, laser Doppler flowmetry for measurement of cutaneous blood flow and 20 MHz ultrasound A-scan for measurement of skin thickness. In spite of homogeneous inflammatory responses, significant differences in the severity of the injury to the skin barrier function caused by the different irritants were found. Also significant differences between irritants were found in the time course of development of maximum irritant reactions. Bioengineering methods indicating inflammatory responses (measurement of blood flow and skin thickness) were helpful in quantifying the irritant response in general, while bioengineering methods indicating epidermal damage (measurement of TEWL and electrical conductance) were helpful in classifying the individual irritants.

Adult↗

How do serine proteases really work?

Recent advances in genetic engineering have led to a growing acceptance of the fact that enzymes work like other catalysts by reducing the activation barriers of the corresponding reactions. However, the key question about the action of enzymes is not related to the fact that they stabilize transition states but to the question to how they accomplish this task. This work considers the catalytic reaction of serine proteases and demonstrates how one can use a combination of calculations and experimental information to elucidate the key contributions to the catalytic free energy. Recent reports about genetic modifications of the buried aspartic group in serine proteases, which established the large effect of this group (but could not determine its origin), are analyzed. Two independent methods indicate that the buried aspartic group in serine proteases stabilizes the transition state by electrostatic interactions rather than by alternative mechanisms. Simple free energy considerations are used to eliminate the double proton-transfer mechanism (which is depicted in many textbooks as the key catalytic factor in serine proteases). The electrostatic stabilization of the oxyanion side of the transition state is also considered. It is argued that serine proteases and other enzymes work by providing electrostatic complementarity to the changes in charge distribution occurring during the reactions they catalyze.

Kinetics↗

The effect of chemical intravaginal contraceptives and Betadine on Ureaplasma urealyticum.

The purpose of this study was to find a barrier contraceptive agent capable of controlling infections and sexual transmission of Ureaplasma urealyticum from the female genital tract, especially to help reduce nongonococcal urethritis in males caused by this organism. Therefore, the in vitro antimicrobial activity of six intravaginal contraceptives and BetadineR against the eight serotypes of the organism was investigated. The results indicate that some of these contraceptives produce partial inhibition of the Ureaplasma at low dilutions, while BetadineR produces a ureaplasmacidal effect up to dilutions of 1:64. These effects appear not to be due primarily to the pH of these agents. Thus, some of these agents may have a potential role in controlling transmission of Ureaplasma urealyticum.

Contraceptive Agents, Female↗

Herpes simplex virus transmission: condom studies.

The incidence of genital herpes simplex infections has risen at a rapid rate over the past 20 years. Sexually active young adults ask whether condoms will effectively block the transmission of herpes simplex virus from one individual to another. Using a laboratory plunger model to stimulate human coitus, the authors have shown that high concentrations of HSV-2 did not cross the latex or natural membrane condoms that were tested. We have also shown that high concentrations of HSV-2 left in contact with a condom for 8 hr does not penetrate the barrier. This study gives good indirect evidence that condoms block the transmission of herpes simplex virus.

Contraceptive Devices, Male↗

Commentary: methods women can use that may prevent sexually transmitted disease, including HIV.

Although sexually transmitted diseases, including human immunodeficiency virus (HIV), are a major concern for women, few prevention messages are targeted specifically to women. Those that are generally stress abstaining, altering the number or selection of partners, and urging partners to use condoms. But these behaviors may be unrealistic for many women, particularly women who are at highest risk for sexually transmitted diseases, because they require significant changes in life-style or depend on male-controlled condom use. Recommendation of contraceptives for prevention of sexually transmitted diseases depends largely on how well specific methods perform under controlled conditions, either in the laboratory or in clinical trials. Observational studies, which better reflect day-to-day use, indicate that condoms, barriers, and spermicides, used properly and consistently, can provide substantial protection against various sexually transmitted diseases. Condoms can similarly help protect against HIV, but studies of barriers and spermicides are scant and currently inconclusive. Finally, those methods that are controlled by women are consistently more effective in preventing sexually transmitted diseases. Thus, although condoms used well are still the best choice, the imperative for female-controlled methods indicates that diaphragms and spermicides should receive greater emphasis in prevention messages.

Condoms↗

The influence of systemic arterial pressure and intracranial pressure on the development of cerebral vasogenic edema.

The influence of intracranial pressure (ICP), systemic arterial pressure (SAP), and cerebral perfusion pressure (CPP) upon the development of vasogenic cerebral edema is largely unknown. To study their relationship, the authors have produced an osmotic disruption of the blood-brain barrier unilaterally in rabbits by injecting 1 cc/kg of 2M NaCl into the left internal carotid artery. The amount of vasogenic edema produced was assessed by quantitation of the extravasation of Evans blue dye into the area of maximum blood-brain barrier breakdown by means of optical densitometry following formamide extraction. The ICP was measured using a cisterna magna catheter into which mock cerebrospinal fluid could be infused at a predetermined pressure. The SAP was controlled by exsanguination from a femoral artery catheter. In 18 animals in which blood pressure was not controlled, no significant relationship between the ICP and the degree of Evans blue dye extravasation was noted. In these animals, however, a direct relationship between CPP (defined as mean arterial pressure minus mean ICP) and extravasation of Evans blue dye was found (correlation coefficient 0.630; p less than 0.001). When ICP was held constant at 0 to 5 mm Hg in another group of 16 animals and different levels of blood pressure were produced by exsanguination, a significant direct relationship between extravasation of Evans blue dye and the SAP was found (correlation coefficient 0.786; p less than 0.001). In a third group of 20 animals, the blood pressure was held constant at 90 to 100 mm Hg and the ICP was varied between 0 and 75 mm Hg. There was a highly significant result indicating increasing Evans blue dye extravasation with lower levels of ICP (p less than 0.001). Cerebral blood flow determinations by the hydrogen clearance method indicated loss of autoregulation in all animals in the areas of brain injured by intracarotid hypertonic saline. These results indicate that high SAP and low ICP (that is, a large CPP) promote Evans blue dye extravasation in this model of blood-brain barrier disruption. This finding has implications for the management of patients with vasogenic edema.

Animals↗

Reliability of the Cobb angle index derived by traditional and computer assisted methods.

The reliability of the traditional Cobb angle index, which at present exhibits a wide range of reported values, was determined in this study and amounted to a within subject error of +/-4.3 degrees and a between subject error of +/-4.9 degrees. An attempt to pinpoint the source of this variability by investigating the influence of choice of end vertebrae proved inconclusive. The reliability of a computer assisted Cobb angle index, developed to improve measurement accuracy, was also examined and an estimated within subject error of +/-1.5 degrees and a between subject error of +/-1.6 degrees obtained. A comparison of the traditional and computer assisted methods indicates a high correlation between the Cobb angle derived using the two methods when measuring like curves and an improved reliability obtained by the computer method. Such an improvement is worth implementing clinically but of course the availability of a computer and digitizer and a little extra time for an operator to input the X-ray coordinates may be a barrier to its general use.

Diagnostic Errors↗