Effectiveness of an enhanced antibiotic stewardship programme among paediatric patients in a tertiary hospital in Vietnam.

BACKGROUND: In 2016, the Vietnamese Ministry of Health promoted development of antimicrobial stewardship for hospitals. AIM: To evaluate the effectiveness and safety of the enhanced antibiotic stewardship programme (ASP) compared to the original ASP among paediatric patients at a tertiary hospital for infectious diseases in Vietnam. METHODS: An interrupted time-series analysis was conducted to examine antibiotic use in paediatric patients aged 0-17 years admitted to the Hospital for Tropical Diseases in Ho Chi Minh City from April 2016 to March 2020. Outcomes measured were defined daily doses (DDDs) per 1000 patient-days; antibiotic days of therapy (DOT) per 1000 patient-days; percentage of antibiotic use by the World Health Organization Access, Watch, and Reserve (AWaRe) system; Access-to-Watch ratio; and worse clinical outcomes at discharge. FINDINGS: Of 60,172 admissions during the study period, 28,019 received at least one antibiotic (46.6%) during hospital stay. The Watch antibiotics were the most frequently prescribed (78.1% of total antibiotic courses). The enhanced ASP did not improve antibiotic prescribing by DDDs per 1000 patient-days (risk ratio: 1.05; 95% confidence interval: 0.94-1.17) and DOT per 1000 patient-days (1.11; 0.99-1.25) compared to the original ASP. However, the percentage of Access antibiotics prescribed, and the Access-to-Watch ratio increased after the enhanced ASP (1.73; 1.38-2.17). There was no significant difference in worse clinical outcomes at discharge between the original and enhanced ASP (1.25; 0.78-2.00). CONCLUSION: The enhanced ASP had modest impact on antibiotic consumption in the paediatric population despite the improvement of Access antibiotic use and the Access-to-Watch ratio.

Cardiometabolic health after first pregnancy: Associations with social determinants of health. A nuMoM2b-HHS study.

Study objective: This study sought to evaluate the associations between social determinants of health (SDOH) at the time of first pregnancy and subsequent cardiometabolic health, defined as the development of metabolic syndrome. Design: nuMoM2b-HHS (Nulliparous Pregnancy Outcomes Study- Monitoring Mothers-to-Be-Heart Health Study) is an ongoing prospective cohort study. Setting: Eight academic medical centers enrolled and continue to follow participants. Participants: 4484 participants followed a mean of 3.2 years from the time of their first pregnancy. Interventions: N/a. Main outcome measure: Unadjusted and adjusted Poisson regression models with robust standard errors were used to obtain relative risks and 95% confidence intervals estimating the risk of metabolic syndrome for each baseline SDOH. In secondary analyses we examined the associations between SDOH and incident hypertension, obesity, and diabetes mellitus. Results: Metabolic syndrome developed in 13.6% of participants. Higher socioeconomic position at the time of pregnancy was associated with lower rates of metabolic syndrome [income > 200% poverty level aRR 0.55 (95% CI, 0.42-0.71), attainment of a bachelor's degree aRR 0.62 (0.46-0.84) or higher aRR 0.50 (0.35-0.71)], while being single [aRR 1.45 (95% CI, 1.18-1.77)] and having low health literacy were associated with a greater risk of metabolic syndrome [aRR 1.98 (95% CI, 1.28-3.07)]. Conclusions: Over a short interval following first pregnancy, participants accumulated high proportions of cardiovascular risk factors and metabolic syndrome, with some risk associated with SDOH. The impact of interventions addressing SDOH in pregnant people on cardiometabolic health should be tested as a means of reducing health inequities at the population level.

Does Eligibility Classification Matter? Tracking Cardiac Autonomic Function during a Collegiate Soccer Season.

The current study examined differences in heart rate (HR) variability (HRV) across student-athlete eligibility classifications within a men's soccer team. The study also aimed to identify any differences in HRV while competing at home or away. Data collection covered an entire collegiate season, commencing in the preseason and concluding upon elimination from the NCAA Soccer tournament. Comparisons of HR and HRV, paired with self-reported subjective measures, were documented between student-athlete eligibility classifications, home versus away games, and based on soccer position (forward, midfielder, defender, goalkeeper). HR and HRV were similar based on student-athlete eligibility. Heart rate exhibited a small, but statistically significant decrease (ß = -1.7 bpm (95% CI: -2.9, 0.57), p = 0.003) for the away games relative to home. HRV showed a statistically significant increase in the away game setting (ß = 2.1 (95% CI: 0.78, 3.38), p = 0.002). No difference in HRV was observed across eligibility classification. This lack of difference may be attributed to a different perception of stress amongst male athletes. Athletes also exhibited a reduced HRV at home, likely as an indication of their readiness to compete paired with an increased self-confidence, given there was no difference in any subjective measures of mood or stress or between games played away or at home.

Strong, Non-specific Adhesion Using C-Lectin Heterotrimers in a Molluscan Defensive Secretion.

The defensive mucus produced by the slug Arion subfuscus is tough and remarkably sticky. It spreads rapidly and adheres strongly to a wide range of surfaces. The adhesion is equally strong on wettable (glass) and non-wettable (plastic) surfaces. The adhesion appears to depend on a group of proteins that adsorb equally well to a wide range of different natural and artificial surfaces. Prominent among these proteins were those that distinguish the adhesive secretion from the non-adhesive mucus. The adhesive proteins were not washed off by non-ionic detergent. Similarly, the adhesion of the glue as a whole was not affected by this treatment. In contrast, high salt concentrations washed the most abundant adhesive proteins off the surfaces, and correspondingly weakened the glue's attachment. The most abundant of the adhesive proteins were C-lectins, which appear to form heterotrimers. These and other lectin-like proteins in slug glue have a high proportion of aromatic amino acids at conserved locations, and are relatively small and often basic. The aromatic and cationic side chains may provide a powerful combination promoting and maintaining surface adhesion.

Effects of quercetin on exercise performance, physical activity and blood supply in a novel model of sustained hind-limb ischaemia.

BACKGROUND: There are currently few effective drugs to treat the leg symptoms of peripheral arterial disease (PAD). Previous studies have suggested that the nutraceutical, quercetin, can improve exercise performance and reduce pain sensitivity in healthy mice and improve blood supply in a rodent model of acute hind-limb ischaemia. These models may not be relevant to people with PAD. The aim of this study was to examine the effect of quercetin on exercise performance, physical activity and blood supply in a novel mouse model of sustained hind-limb ischaemia. METHODS: Hind-limb ischaemia was induced in 6-month-old male apolipoprotein E-deficient mice using a novel two-stage surgical procedure. Five days after induction of ischaemia, mice were allocated to commence dietary quercetin or a control diet for 4 weeks. The primary outcome was exercise performance evaluated using a treadmill test. Other outcomes included physical activity, estimated by an open field test, and hind-limb blood supply, assessed by laser Doppler monitoring. RESULTS: A sustained reduction in relative limb blood supply (P < 0.001) was achieved consistently in all 48 mice before allocation to a control (n = 24) or quercetin (n = 24) diet. Quercetin did not improve exercise performance (P = 0.785), physical activity (P = 0.151) or relative limb blood supply (P = 0.954) over the 4-week assessment period. CONCLUSION: These data suggest that quercetin does not improve exercise performance, physical activity or limb blood supply in mice with sustained hind-limb ischaemia, and therefore is unlikely be an effective treatment for PAD.

Structure-based discovery of interleukin-33 inhibitors: a pharmacophore modelling, molecular docking, and molecular dynamics simulation approach.

Interleukin (IL)-33 is a new cytokine of the IL-1 family that is related to several inflammatory and autoimmune diseases. IL-33 binds to its ST2 receptor and leads to biological responses thereof. Currently, no drugs have been approved for the treatment of IL-33 related diseases. The aim of this study was to search for small molecules that inhibit the protein-protein interaction between IL-33 and ST2. A virtual screening was first performed to identify potential molecules that can bind IL-33. By analysing the interactions between key residues in the complex of IL-33/ST2, two pharmacophore hypotheses were then generated based on the 'mimicry' and 'pair-rule' principles. From a database of 62,074 compounds, 60 molecules satisfying the pharmacophore models were identified and docked to IL-33. Among 35 compounds successfully docked into the protein, 9 potential ligands in complex with IL-33 were selected for further analysis by molecular dynamics simulations. Based on the stability of the complexes and the interactions of each ligand with the key residues of IL-33, two compounds DB00158 and DB00642 were identified as the most potential inhibitors that can be further investigated as promising novel IL-33 inhibitory drugs.

High-Resolution MRI for Evaluation of Ventriculostomy Tubes: Assessment of Positioning and Proximal Patency.

BACKGROUND AND PURPOSE: Imaging evaluation of ventriculostomy tubes, despite the frequency of malfunction, has remained inadequate due to the absence of a systematic way of assessing the catheter itself. In this retrospective review, we assessed the utility of high-resolution 3D MR imaging techniques, including CISS and volumetric interpolated breath-hold examination sequences, in the evaluation of ventriculostomy catheters. MATERIALS AND METHODS: We performed a retrospective review of 23 clinical MR imaging cases of shunted hydrocephalus spanning a 3-year period, all depicting ventriculostomy catheters. The MR imaging examinations included isotropic CISS and volumetric interpolated breath-hold examination sequences performed with and without contrast. These were independently evaluated by 2 neuroradiologists with respect to the catheter course, side hole position, relationship of the side holes to the ventricles, patency, and the presence or absence of intraluminal debris. RESULTS: The catheter tip was best seen on isotropic CISS sequences reformatted in an oblique plane, and side holes were visualized as CSF signal defects along the catheter wall in 10/23 (43%) cases. The relationship of the catheter side holes to the ventricles was seen in 47% of cases and was best visualized on the coronal CISS sequences. Catheter patency was confirmed in 12/23 (52%) cases, while the other 48% were notable for T2 hypointense filling defects compatible with luminal obstruction. Enhancement of some of these filling defects on imaging is suggestive of choroid plexus ingrowth rather than debris. CONCLUSIONS: High-resolution 3D MR imaging using isotropic CISS sequences allows systematic evaluation of catheter positioning, patency, and potential etiologic differentiation of filling defects when shunt dysfunction is suspected.

Between session reliability of intramuscular electromyography for segments of gluteus medius and minimus during gait and stepping tasks.

Between-session reliability of electromyographic data is important for confidence in interpreting the role of muscles in functional tasks but critical if these data are to be compared before and after an intervention that seeks to change pathological patterns of muscle activity. The gluteus medius (GMed) and minimus (GMin) are known to have functionally discrete segments that are highly active during stance phase of gait and stepping tasks. This study measured the between-session reliability of activity patterns, mean amplitudes and time to peak (TTP) activity of these muscle segments. Intramuscular electrodes were placed in 3 segments of GMed and 2 segments of GMin in 10 healthy young adults for each of two testing sessions held two weeks apart. Participants completed six repetitions of comfortable speed walking trials, step-up and step-down tasks with activity patterns for each muscle segment time- and amplitude-normalized and averaged across trials. Re-test reliability for was high for activity patterns (coefficient of mean correlation ranging from 0.890 to 0.998) across all tasks and muscle segments and only two pairwise comparisons showing differences in amplitude between sessions. With standardized data collection and analysis procedures, GMed and GMin muscle segment activity patterns show good between-session reliability for weightbearing tasks.

Quantum coherence engineering in the integer quantum Hall regime.

We present an experiment where the quantum coherence in the edge states of the integer quantum Hall regime is tuned with a decoupling gate. The coherence length is determined by measuring the visibility of quantum interferences in a Mach-Zehnder interferometer as a function of temperature, in the quantum Hall regime at a filling factor 2. The temperature dependence of the coherence length can be varied by a factor of 2. The strengthening of the phase coherence at finite temperature is shown to arise from a reduction of the coupling between copropagating edge states. This opens the way for a strong improvement of the phase coherence of quantum Hall systems. The decoupling gate also allows us to investigate how interedge state coupling influences the quantum interferences' dependence on the injection bias. We find that the finite bias visibility can be decomposed into two contributions: a Gaussian envelope which is surprisingly insensitive to the coupling, and a beating component which, on the contrary, is strongly affected by the coupling.

Plerixafor in poor stem cell mobilizers: the Belgian Compassionate Use Program.

INTRODUCTION: Currently available stem cell mobilizing regimens (G-CSF +/- chemotherapy) show high failure rates, especially in heavily pretreated patients. Plerixafor, a new stem cell mobilizing agent blocking the CXCR4-SDF-1 interaction, offers a new strategy for stem cell mobilization, especially in poor mobilizers.This study reports on the outcome of the Belgian compassionate use program (CUP). MATERIALS AND METHODS: Between July 2008 and July 2009, 14 Belgian transplant centres participated in plerixafor CUP. In total, 22 poor stem cell mobilizers were included. Patients who previously failed stem cell mobilization received a combination of G-CSF (morning of Day 1-5) and plerixafor (evening of Day 4). Apheresis was performed on Day 5. G-CSF, plerixafor and apheresis were continued until at least 2 x 10(6)/kg CD34+ cells were obtained in a maximum of 3 collections. RESULTS: A mean of 2 plerixafor administrations was needed to reach > or = 2 x 10(6)/kg CD34+ cells. The overall cumulative success rate (defined as the proportion of patients achieving a successful collection after a maximum of 3 apheresis days) was 64%. Half of the heavily pretreated patients ( 3 prior chemotherapy regimens) could be mobilized successfully. Patients who received < or = 2 prior chemotherapy regimens mobilized successfully in 75% of the cases. Thirteen patients (59.1%) underwent autologous stem cell transplantation with normal neutrophil and platelet recovery times. CONCLUSION: For patients failing previous mobilization attempts, the combination of plerixafor and G-CSF is a successful mobilizing strategy, even in poor mobilizers who received > or = 3 prior chemotherapy regimens.

Herpes simplex virus type 1 thymidine kinase sequence fused to the lacz gene increases levels of {beta}-galactosidase activity per genome of high-capacity but not first-generation adenoviral vectors in vitro and in vivo.

Increased transgene expression per vector genome is an important goal in the optimization of viral vectors for gene therapy. Herein we demonstrate that herpes simplex virus type 1 (HSV1) thymidine kinase (TK) gene sequences (1,131 bp) fused to the 3' end of lacZ increase transgene expression from high-capacity adenoviral vectors (HCAd), but not from first-generation (Ad) vectors. The woodchuck hepatitis virus posttranscriptional regulatory element (WPRE), in contrast, increased transgene expression levels from Ad but not HCAd vectors. The differential activity of the HSV1 TK gene and WPRE sequences was detected both in vitro and in vivo and suggests potentially different mechanisms of action or the interaction of these elements with vector genomic sequences.

Urinary incontinence after radical retropubic prostatectomy is not related to patient body mass index.

To determine if a relationship exists between patient body habitus and urinary incontinence after radical retropubic prostatectomy (RRP) for clinically localized prostate cancer. A questionnaire developed by combining parts of lower urinary tract symptom questionnaires concerning voiding symptoms after RRP was mailed to 268 consecutive patients who underwent RRP over a 2-year period. The interval between surgery and questionnaire administration was greater than 24 months for each patient. No interval was greater than 54 months. The questionnaire attempted to overcome the subjectivity of patient documented urinary incontinence by probing different aspects of each patient's voiding symptoms. Body mass index (BMI), obtained from preoperative anesthesia records, was used as the measurement for body habitus. Pearson correlations were used to determine relationships between BMI and responses and the independent t-test was used to determine differences between grouped responses and BMI. One hundred and eighty-two of 268 (68%) questionnaires were returned. No relationship was detected between BMI and patient estimates of urinary control, QOL relating to urinary symptoms, severity of stress incontinence, or use of protection (pad use). As well, no statistically significant relationship was found between BMI and a patient's willingness to undergo RRP again, based on his voiding symptoms, if given the choice. In conclusion, although patient body habitus may be related to other clinical outcomes following RRP, there does not appear to be a relationship of BMI to post-RRP urinary incontinence.

Pointillist nevi.

BACKGROUND: Atypical melanocytic nevi and cutaneous melanoma are often marked by variation in color. However, there are examples of "benign" explanations for irregularities in pigmentation, such as perifollicular hypopigmentation or hyperpigmentation. OBJECTIVE: The purpose of this study was to correlate the clinical and histologic features of 3 unusual melanocytic nevi consisting exclusively of multiple, tiny, dark brown to black dots on a skin-colored background, which we have termed pointillist nevi. METHODS: Histologic examination was performed of the single pointillist nevus from each of 3 patients (all women; aged 28, 39, and 47 years). RESULTS: The diameters of the pointillist nevi were 2, 3.5, and 5.5 mm. Individual dots were approximately 0.1-0.25 mm. Each of the 3 nevi showed a different histologic correlate for the dots, either (1) discrete, densely pigmented, junctional melanocytic nests; (2) isolated dermal pigmented melanocytic nests; or (3) discrete clusters of melanophages in the papillary dermis. CONCLUSION: Pointillist nevi are benign melanocytic nevi with histologic correlates similar to those of the "brown globules" observed by dermoscopy in uniformly pigmented nevi. However, the dots seen in pointillist nevi can be visualized without magnification. The clinical and histologic features of pointillist nevi add to the spectrum of unusual patterns of pigmentation that may be encountered in benign melanocytic lesions.

Unusual halo nevi--darkening rather than lightening of the central nevus.

Although the classic halo nevus is a brown nevus with a surrounding rim of depigmentation, i.e. a stage I halo nevus, these nevi can have several clinical stages. The central nevus may lose its pigmentation and appear pink with a surrounding halo (stage II), the central papule may disappear leading to a circular area of depigmentation (stage III) or the depigmented area may repigment (stage IV), leaving no trace of its prior existence. Herein we describe an unusual phenomenon--darkening of the central nevus rather than lightening--following the appearance of the halo phenomenon. An 18-year-old boy who had multiple atypical nevi developed multiple halo nevi beginning at the age of 12 years. Following the appearance of the peripheral halos, 2 of his nevi that were originally solid medium brown in color darkened and the hyperpigmentation had a reticulated pattern with perifollicular sparing. One possible explanation is a postinflammatory hyperpigmentation induced by the infiltrating lymphocytes.

Percutaneous core biopsy of the breast: correlates of anxiety.

RATIONALE AND OBJECTIVES: The authors performed this study to investigate the level of patient anxiety immediately preceding breast biopsy and examined potential clinical and demographic correlates of anxiety. MATERIALS AND METHODS: The authors evaluated 102 women who were referred to a radiology breast clinic to undergo breast biopsy. The women were assessed with a self-report of demographic and medical items and the State Trait Anxiety Inventory (STAI) immediately before their biopsy. The STAI also was administered at 1 and 5 days after biopsy. RESULTS: The participants' mean state anxiety T score as measured with the State Trait Anxiety Inventory was 71.1 (standard deviation, 7.2). Multiple regression analysis was performed to determine the correlates of state anxiety. The variables that showed the strongest correlation with state anxiety were trait anxiety, being concerned about the results of biopsy, education (less education was associated with more anxiety), age (an older age was associated with more anxiety), and number of relatives with breast cancer. Given the expected overlap (r = 0.55) between state and trait anxiety, a second regression analysis was performed that controlled for trait anxiety. The results of this analysis also identified age, being concerned about the results of the biopsy. and number of relatives with breast cancer as relevant correlates of state anxiety. CONCLUSION: Overall, the results give some indication of the characteristics of women likely to be most anxious before biopsy. Future research should assess the effectiveness of different strategies for addressing situational anxiety.

The epidemiology and disease burden of rotavirus in Vietnam: sentinel surveillance at 6 hospitals.

The disease burden of rotavirus diarrhea in Vietnam was assessed by surveillance of children <5 years old who were hospitalized for diarrhea at 3 centers in the north and 3 centers in the south. Rotavirus was identified in 56% (range, 47%-60%) of the 5768 patients surveyed between July 1998 and June 2000. G-typing of the first 224 strains indicated that only 2% were non-typeable, 9% were in mixed infections, and the remainder were of the common serotypes G1, G2, G3, G4, and G9. In Vietnam, diarrhea accounts for 9880 deaths per year, which is approximately 15% of all deaths among children <5 years old, or 6.5 deaths per 1000 children. If even 50% of these diarrhea-related deaths in Vietnam were due to rotavirus, the number would represent 4%-8% of all deaths among children <5 years old, 2700-5400 rotavirus-related deaths per year, and 1 death per 280-560 children during the first 5 years of life. Thus, the disease burden of rotavirus in Vietnam is substantial, and programs to encourage the use of oral rehydration should be encouraged while efforts to develop vaccines continue.

17 alpha androstenediol inhibition of breast tumor cell proliferation in estrogen receptor-positive and -negative cell lines.

Androstene-3beta, 17alpha-diol (17alpha-AED) inhibits DNA synthesis and induces apoptosis in several myeloid cancer cell lines. The purpose of this study was to determine if 17alpha-AED inhibition of human breast carcinoma cell proliferation is dependent on the estrogen or androgen receptor. At concentrations of 12.5 to 50 x 10(-9) M 17alpha-AED inhibited the proliferation of ZR75-1, estrogen receptor-positive (ER+) cells, by 54% to 68%. Further, 17alpha-AED inhibited MDA-MB231, estrogen receptor-negative (ER-) cells, by 33.6% to 56.0%. The inhibitory effect was dose dependent with a minimal effective inhibitory dose at 12.5x10(-9) M for both cell lines. Both 17beta-AED and estradiol potentiate the inhibitory effect of 17alpha-AED on ER+ cells at lower doses (3.13 to 6.25 x 10(-9) M) where 17alpha-AED alone was not inhibitory. The inhibitory action of 17alpha-AED on human mammary carcinomas appears to be independent of either the alpha estrogen or the androgen receptors.

Redistribution of Bax is an early step in an apoptotic pathway leading to germ cell death in rats, triggered by mild testicular hyperthermia.

Programmed cell death occurs spontaneously during spermatogenesis and can be induced in a cell- and stage-specific manner by mild testicular hyperthermia. Studies using transgenic mice suggest the involvement of Bcl-2 proteins in regulating germ cell apoptosis. To delineate further the pathways involved, we examined the temporal changes in proapoptotic Bax and antiapoptotic Bcl-2 in rat testes after transient exposure to heat (43 degrees C for 15 min). Germ cell apoptosis, involving exclusively early (I-IV) and late (XII-XIV) stages, was activated within 6 h. Initiation of apoptosis was preceded by a redistribution of Bax from a cytoplasmic to perinuclear localization within 0.5 h of heating as assessed by immunocytochemical methods. In contrast, Bcl-2 is distributed both in the cytoplasm and nucleus in those cell types susceptible to heat-induced apoptosis. Despite the striking redistribution, Bax levels remained unchanged as determined by Western analysis; Bcl-2 levels increased significantly by 6 h after heat exposure. Reverse transcription-polymerase chain reaction analysis indicated no change in either Bax or Bcl-2 mRNA levels in response to heat, suggesting the involvement of post-transcriptional rather than transcriptional mechanisms mediating their activity. The marked subcellular redistribution of Bax prior to activation of apoptosis and the increase in Bcl-2 suggest an involvement of Bcl-2 family members in heat-induced apoptotic death of germ cells.

Long-term effects of triptolide on spermatogenesis, epididymal sperm function, and fertility in male rats.

Prior studies had suggested that triptolide, a diterpene triepoxide isolated from a Chinese medicinal plant, might be an attractive candidate as a post-testicular male contraceptive agent. Despite the promise that triptolide would not affect testis function, nagging concerns remained that a delayed onset of testicular effect might exist. The objectives of this study were to assess the effects of relatively longer treatment duration of triptolide on fertility, spermatogenesis, and epididymal sperm pathophysiology; and to evaluate the reversibility of these effects after the cessation of treatment. Adult male Sprague-Dawley rats were fed daily with either 30% gum acacia as a vehicle control (n = 12) or 100 microg/kg body weight (BW) of triptolide for 82 days (n = 12) followed by a recovery period of up to 14 weeks (n = 6). At the end of the treatment period, all rats treated with triptolide were sterile. Cauda epididymal sperm content decreased by 84.8% and sperm motility was reduced to zero. In addition, virtually all cauda epididymal sperm in the triptolide-treated group exhibited severe structural abnormalities. The most striking changes observed were head-tail separation, premature chromatin decondensation of sperm nuclei, a complete absence of the plasma membrane of the entire middle and principle pieces, disorganization of the mitochondrial sheath, and aggregation of many sperm tails. Longer treatment duration of triptolide also affected spermatogenesis, with marked variability in the response of individual animals. The degree of damage ranged from apparently normal-looking seminiferous tubules to flattened seminiferous epithelium lined by a single layer of cells consisting of Sertoli cells and a few spermatogonia. Affected tubules exhibited intraepithelial vacuoles of varying sizes, multinucleated giant cells, germ cell exfoliation, and tubular atrophy. Recovery occurred as early as 6 weeks after cessation of treatment. By 14 weeks, 4 out of 6 triptolide-treated males were fertile and the females that were impregnated by 3 out of 4 triptolide-treated male rats produced apparently normal litters. These results suggest that triptolide has 2 phenotypic effects on mature and maturing germ cells. The first action appears earlier and manifests mainly in epididymal sperm. The second action presumably is directly on germ cells in testis and causes a variable impairment of spermatogenesis that may not be completely reversible. It is unclear if the earlier effect is a delayed manifestation of subtle testicular injury or post-testicular action.