Infection of mice with the murine retrovirus mixture LP-BM5 caused a retroviral infection with many similarities to human HIV infection. We have reported alterations in hepatic drug metabolism which progressed during the course of this infection. Hexobarbital-induced sleep time increased 1.5-2.2-fold above uninfected controls after 10 to 19 weeks post infection. Inhibition of spectral cytochrome P-450 levels by 25 to 30% was observed between 15 and 17 weeks post-infection, and there were changes in specific microsomal enzyme activities. The microsomal cocaine demethylase activity was reduced by 40%, whereas cytosolic enzyme activities were increased by 1.5-2.0-fold. These alterations may contribute to the altered metabolism of drugs of abuse reported in MAIDS mice. The mechanism for these alterations is not known, although the effects correspond temporally to reported infiltration of the liver with immunoblasts and plasma cells. This suggests a role for the immune system or for mediators released by cells of the immune system which could account for these observations. An understanding of the effects of infection on drug metabolism is important because of their impact on the efficacy and safety of drugs for use in AIDS patients).

Animals↗

PubMedDate not supplied

Puupehenone, a cytotoxic metabolite from a deep water marine sponge, Stronglyophora hartmani.

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Animals↗

PubMedDate not supplied

Associations between pelvic anatomy, height and year of birth of men and women in Belfast.

Standardized radiological pelvimetry was used to examine 242 male and 314 female adults attending the out-patient departments of the Royal Victoria Hospital, Belfast, Seven indices of pelvic size and shape were measured from X-rays on each individual together with social and biological factors including age, height and year of birth. The aims were to quantify any differences in pelvic anatomy between the sexes and to measure correlations between these pelvic indices and selected biosocial factors. Pelvic indices for men and women of similar stature were significantly different, with the exception of the brim index, and these anatomical changes were correlated with year of birth. The similarity of the findings in both sexes suggests common environmental factors such as nutrition are the most likely causes, rather than factors specifically associated with pregnancy and childbirth.

Adult↗

PubMedDate not supplied

Brief report: relationship between HIV infection and WPPSI-R performance in preschool-age children.

OBJECTIVE: To determine the neurodevelopmental effects of perinatally acquired HIV infection on children of preschool age. METHODS: Participants included 40 children infected with HIV between the ages of three and five and an equal number of noninfected controls individually matched according to ethnicity, age, sex, and prenatal drug exposure. Participants were administered the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R), upon which an analysis of subtest distribution was conducted. RESULTS: Whereas both groups evidenced mean IQ and subtest scores significantly below published norms, an effect for HIV group status was not found when a factor combining Performance IQ (PIQ) and Verbal IQ (VIQ) was analyzed. However, the group infected with HIV scored significantly lower than controls on the Block Design subtest. CONCLUSIONS: Gross cognitive deficits are not evident among preschool children infected with HIV relative to matched controls. However, this study does provides some evidence for more focal deficits. Further investigation with older children should be conducted.

Case-Control Studies↗

PubMedDate not supplied

The effect of tamoxifen on spermatogenesis in subfertile men.

Forty three subfertile male patients exhibiting a wide range of sperm counts received Tamoxifen (Nolvadex, I.C.I.) 20 mg daily for six months continuously; nine pregnancies resulted, a rate of 21 per cent. Although a significant improvement in sperm output occurred in three patients with initial sperm counts of less than 20 x 10(6)/ml the response was most marked in those with an initial count of less than 5 x 10(6)/ml and four pregnancies occurred in this latter group. Patients whose initial count was greater than 20 million per ml showed no significant response and four exhibited a steady fall in sperm output. No correlation was found between the response to treatment and basal serum levels of FSH, LH, testosterone and prolactin. Four markedly oligozoospermic patients with a significantly elevated FSH, normally associated with severe tubular dysfunction, showed a pronounced increase in sperm count. Seven patients (16 per cent) experienced minor side effects.

Hormones↗

PubMedDate not supplied

Persistent effects of pentoxifylline on human sperm motility, after drug removal, in normozoospermic and asthenozoospermic individuals.

The aim of the study was to compare the in vitro effect of pentoxifylline on human sperm motility when added prior to sperm selection and the persistence of the response after drug removal in normo- and asthenozoospermic individuals. The sperm samples were obtained from 22 men who were repeatedly asthenozoospermic or normozoospermic. Sperm movement was measured using computer-assisted semen analysis over 180 min. Percentage motility and progressive motility were increased in both normo- and asthenozoospermic samples (P < 0.05). Curvilinear velocity, amplitude of lateral head displacement and beat-cross frequency were increased in both groups (P < 0.05). Straight-line velocity was increased significantly in the normozoospermic group only. In both normo- and asthenozoospermic individuals pentoxifylline appeared to enhance sperm motility for at least 180 min after drug removal. This should prevent any potentially toxic effects of the drug on oocytes if it is used to enhance sperm motility during in vitro fertilization.

Humans↗

PubMedDate not supplied

The effects of pentoxifylline on the generation of reactive oxygen species and lipid peroxidation in human spermatozoa.

The aims of this study were to compare the in vitro effects of 3.6 mM and 7.2 mM pentoxifylline on the ability of spermatozoa to generate reactive oxygen species (ROS) and on lipid peroxidation (LPO). Semen samples were obtained from 10 asthenozoospermic men who had been previously identified as producing ROS after addition of Phorbol 12-myristate 13-acetate (PMA) during the screening of patients attending with male factor infertility. Spermatozoa were prepared by a swim-up technique from unprocessed semen and divided into 3 aliquots. To the control aliquot [A] an equal volume of BWW medium was added. To aliquots B and C an equal volume of BWW medium containing pentoxifylline was added to obtain final concentrations of 3.6 and 7.2 mM, respectively. ROS production was measured from peak luminescence (mV 10(-7) sperm) using a lucigenin chemiluminescent probe. LPO was also measured in the medium surrounding the spermatozoa after 30 min exposure to pentoxifylline using the thiobarbituric acid (TBA) assay for malondialdehyde (MDA). The reduction in ROS production was significantly greater in the samples exposed to 7.2 mM pentoxifylline as compared with the control and 3.6 mM pentoxifylline samples. There was no significant difference in peak luminescence between control and 3.6 mM pentoxifylline specimens. Both concentrations of pentoxifylline caused comparable reductions in MDA concentration in the medium (P < 0.05) surrounding the spermatozoa compared with control after 30 min exposure. Extracellular ROS generation may damage surrounding healthy spermatozoa. These findings suggest that higher concentrations of pentoxifylline are protective against ROS release in susceptible spermatozoa and may also reduce collateral LPO.

Humans↗

PubMedDate not supplied

Human sperm morphology and in vitro fertilization: sperm tail defects are prognostic for fertilization failure.

The aim of this study was to determine the relationship between sperm morphology and fertilization rates in vitro. Semen samples were obtained from 50 couples undergoing IVF treatment. Sperm morphology was classified by strict criteria (Tygerberg) according to head, midpiece and tail defects in neat semen and after sperm selection by Percoll gradient centrifugation. Percoll preparation significantly increased the percentage of sperm with normal morphology from 13 to 20%. However, the greatest single regression coefficient was observed with the percentage of sperm with tail defects and correlated negatively with fertilization rates in vitro both before and after Percoll preparation. Therefore, tail morphology may be of value as a prognostic factor in assisted conception both before and after Percoll preparation.

Female↗

PubMedDate not supplied

Influence of pentoxifylline on human sperm motility in asthenozoospermic individuals using computer-assisted analysis.

This study was conducted to evaluate the in vitro effects of pentoxifylline on sperm motility from asthenozoospermic men. The sperm were prepared by a swim-up technique from the unprocessed semen. After centrifugation, sperm were resuspended in the presence or absence (controls) of 3.6 mM pentoxifylline in Earle's solution for up to 180 min. Sperm motility was measured using computer-assisted (Hamilton-Thorn Research) semen analysis. Pentoxifylline significantly increased the numbers of motile (+28-80%) and progressively motile (+54-117%) sperm over the 180 min studied. These changes were accompanied by increases in the progressive velocity (VSL, +11-44%) and curvilinear velocity (VCL, +12-22%) up to 120 min after exposure to the drug. Concomitant changes were observed in the amplitude of lateral head displacement (ALH, +5-17%) up to 60 min and the beat cross frequency (+16-34%) between 60 and 180 min. The results suggest that pentoxifylline consistently enhances both the numbers of motile and progressively motile sperm and the quality of their movement.

Humans↗

PubMedDate not supplied

Reproducibility of sperm motility measurements in asthenozoospermic and normozoospermic individuals using the Hamilton-Thorn motility analyzer.

Computer-assisted semen analysis provides a useful, quantitative method for analyzing sperm movement parameters. However, few experimental data have been published on the measurement characteristics of CASA. This study measured the reproducibility of measurements of sperm motility using a Hamilton-Thorn motility analyzer. Twenty normozoospermic and 20 asthenozoospermic patients provided semen samples. Ten samples from each group were analyzed as unprocessed semen; the remainder were analyzed after washing. An aliquot from each sample was analyzed by CASA 10 times over an 18-min period. The mean coefficient of variation for all sperm motility parameters was less than 10%, except for the percentage of motile cells in the asthenozoospermic unprocessed samples, which was 17.1%. The mean coefficient of variation for percentage motility was reduced to 9.6% in the washed asthenospermic group. Other motility parameters were unaltered by washing in the asthenospermic samples. There were no substantial differences between the washed and unwashed normospermic measurements. Normospermic samples showed better reproducibility in measurement than asthenozoospermic samples. Washing reduced the difference, probably because of the removal of debris in the asthenozoospermic samples. The results indicate that serial measurements of sperm motility in both unprocessed and washed semen samples can be reliably made using the Hamilton-Thorn motility analyzer, and that reproducibility can be improved in asthenospermic samples by washing.

Humans↗

PubMedDate not supplied

Reactive oxygen species generation in human sperm: luminol and lucigenin chemiluminescence probes.

The objective of this study was to compare measurements of reactive oxygen species (ROS) generation from human spermatozoa in vitro using the luminol and lucigenin chemiluminescent probes. Luminol reacts with a variety of reactive oxygen species (H2O2, O2-, OH) and allows both intra- and extracellular ROS to be measured. Lucigenin, however, yields a chemiluminescence that is more specific for superoxide anions released extracellularly. Therefore, measurements made with both probes on the same samples should allow the intra- and extracellular components of ROS generation to be identified. Sperm samples from 47 men were divided into two equal aliquots, then processed by centrifugation and swim-up. Following further division into aliquots and the addition of the two chemiluminescent probes, Phorbol 12-myristate 13-acetate was added to trigger ROS release. Forty three percent of the sperm samples generated detectable levels of ROS. In the centrifuged preparations luminol produced a significantly higher peak luminescence than lucigenin. However, the sperm prepared by swim-up showed no significant differences in peak luminescence between luminol and lucigenin. The higher level of ROS generation produced by centrifugation may be due to membrane disruption or possibly the use of unfractionated cell suspensions. Extracellular ROS generation is more clinically important because surrounding healthy spermatozoa may be damaged. Therefore the lucigenin probe may be a more useful diagnostic tool than luminol for identifying sperm at risk of peroxidative damage after swim up preparation. The patients identified in this way may benefit from the addition of ROS scavengers to the culture medium in order to protect healthy sperm from collateral damage.

Acridines↗

PubMedDate not supplied

Electronic dental anesthesia for restorative dentistry.

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Anesthesia, Dental↗