Metabolism and biochemical effects of 3,3',4,4'-tetrachlorobiphenyl in pregnant and fetal rats

The metabolism and distribution of a single oral dose of 25 mumol 14C-labelled 3,3',4,4'-tetrachlorobiphenyl (14C-TCB) were investigated in pregnant female Wistar rats and their fetuses. TCB was administered on day 13 of gestation and the elimination was followed for 7 days. Non-pregnant rats were treated similarly for comparison. Fecal elimination of 14C-TCB derived radioactivity was significantly lower in pregnant rats than in non-pregnant rats. The major metabolite found in adult liver and plasma, placental tissue, whole fetuses and fetal plasma was 3,3',4',5-tetrachloro-4-biphenylol (4-OH-TCB). Tissue levels (liver, abdominal fat, skin, skeletal muscle, kidney and plasma) of 14C-TCB-derived radioactivity declined by 65-85% over a 7-day period following administration in the adult animals. However, 14C-TCB-derived radioactivity accumulated more than 100-fold in the fetuses over the same time period, and GC/MS analysis revealed that the fetal accumulation in radioactivity was due primarily to 4-OH-TCB, and not the parent compound. On day 20 of gestation, concentrations of 4-OH-TCB were 14 times greater in fetal plasma than maternal plasma. Treatment with 14C-TCB significantly reduced plasma thyroxine levels by at least 28% up to 7 days after administration in non-pregnant animals and up to 4 days after administration in pregnant rats (31% decrease). By 7 days after administration plasma thyroxine levels had returned to control levels in the TCB-treated pregnant rats. However, fetal plasma thyroxine levels were significantly decreased by 35% in fetuses from 14C-TCB-treated dams 7 days after TCB administration. Hepatic microsomal ethoxyresorufin-O-deethylase (EROD) activity was significantly induced in TCB-treated dams relative to controls at 4 and 7 days after administration, while no EROD activity was detected in hepatic microsomes from control or TCB treated fetal rats at day 20 of gestation. These data suggest that hydroxylated metabolites of polychlorinated biphenyls may play a role in the development toxicity of these compounds.     

Monoamine oxidase in developing chick retina

The developmental changes in monoamine oxidase (MAO) activities towards 5-hydroxytryptamine (5-HT) and beta-phenylethylamine (PEA) in chick retina were investigated. The whole pattern of the developmental changes in MAO activity towards 5-HT was similar to that towards PEA, even though the activity towards 5-HT was much lower than that towards PEA during the period from the 12th day of incubation to the 14th day after hatching. The MAO activities on the 12th day of incubation were low and increased remarkably until the 18th day of incubation. Then they remained unchanged until the 7th day after hatching; therefore, they decreased. The activities measured on the 14th day after hatching are on the same level as those of an adult. The multiplicity of MAO in the retinae of a chick on the 12th day of incubation and of an adult was also studied with specific inhibitors. The result showed that the major part of MAO in chick retina is type B enzyme; that type A MAO in the retina of an adult is, however, relatively higher than that in the retina of the embryo on the 12th day of incubation. It was found that an appreciable amount of MAO activity towards 5-HT in chick retina is due to type B MAO.     

Insulin synthesis in chick embryo retinas during development

Retinas of chick embryos contain insulin and further, are capable of synthesizing it, as demonstrated by incubating retinas at different ages (7th-18th day) with [3H]leucine. The synthesized radioactive insulin was isolated and assayed by means of a HPLC procedure. The synthesis of insulin was found to be highest in the youngest retinas studied (day 7), afterwards it declined with age except for an increment found at 14-15 day. Explants of chick embryo retinas, cultured in vitro, rapidly degraded insulin. Nevertheless, the content of immunoreactive insulin in retinal explants diminished slowly with the age of culture, so that, after 8 days of incubation, it was about 60% of the content found in the retinas at the beginning of incubation. This was proof that cultured explants are capable of efficiently synthesizing insulin. The synthesized [3H]insulin was released from explants into the medium. This was evident also after 6-8 days in culture.     

Laminin 5 can promote assembly of the lamina densa in the skin equivalent model

Skin equivalents were prepared by culturing human keratinocytes on the surface of type I collagen gel contracted by human skin fibroblasts (dermal equivalents) and by raising the gel to an air-liquid interface. A stratified squamous epithelium was formed with a well-differentiated cornified layer at the top of keratinocyte layers within 7 days after plating of the keratinocytes on the dermal equivalents. Although major basement membrane components such as collagens IV and VII and laminin 5 were detected immunohistochemically at the dermal-epidermal junction, a lamina densa was rarely observed by electron microscopy even in 14-day skin equivalents. When laminin 5 (1, 5 or 20 microg/ml) was added to the culture medium on day 7 through day 14, types IV and VII collagens at the dermal-epidermal junction stained more strongly by immunohistochemistry compared with the control. Patches of lamina densa were present along the epidermal-dermal junction, and vesicles containing electron-opaque sheets approximately 0.6 microm in diameter that reacted with anti-collagen IV antibody were also observed in basal keratinocytes in 14-day skin equivalents by electron microscopy. Morphometric analysis showed that the total length of lamina densa along the dermal-epidermal junction as well as in the vesicles increased up to 180%, 230% or 520% of control cultures by the addition of laminin 5 (1, 5 or 20 microg/ml, respectively). These results suggest that laminin 5 accelerates formation of the lamina densa along the dermal-epidermal junction of the skin equivalents, depending on the concentration of laminin 5 supplemented exogenously.     

Differences and similarities in adjuvant chemotherapy in mouse and man

Supernatants obtained after incubation of tumor patient lymphocytes with the homologous tumor-associated antigen (TAA) elicit adherence inhibition in normal guinea pig peritoneal cells. From 37 tested patients with different carcinomas, the supernatants of 30 caused more than 10 per cent adherence inhibition (breast cancer 11/11, lung cancer 7/8, colon cancer 6/7, stomach cancer 6/11). Besides 40 healthy blood donors were tested to a panel of TAA. There was a reactivity more than 10 per cent only in 2 cases. The supernatants of 14 patients with nonmalignant disorders produced adherence inhibition more than 10 per cent in 2 cases. By incubation of tumor patient lymphocytes with the human encephalitogenic protein the supernatants of 19/27 patients elicited a positive reaction. The results suggest that anti-tumor immunity can be detected in an indirect heterologous adherence inhibition system.     

Clinical efficacy of clarithromycin against uterine cervical and pharyngeal Chlamydia trachomatis and the sensitivity of polymerase chain reaction to detect C. trachomatis at various time points after treatment

The detection and eradication of pharyngeal Chlamydia trachomatis in patients with chlamydial uterine cervicitis (commercial sex workers and others) were investigated. Pharyngeal C. trachomatis was detected in 75.0% of the commercial sex workers and in 21.9% of the other subjects. All the pharyngeal C. trachomatis-positive patients had a past history of orogenital contact. Chlamydial infection was treated with clarithromycin for 7 or 14 days. The presence of C. trachomatis was determined by polymerase chain reaction (PCR) on days 8, 15, and 22 after completion of the treatment. In the 7-day treatment group, the eradication rate of pharyngeal C. trachomatis was 53.3%, 56.7%, and 60.0% on days 8, 15, and 22, respectively, after completion of the treatment, while the eradication rate of cervical C. trachomatis was 83.3%, 96.7%, and 100% on days 8, 15, and 22, respectively. The eradication rate of pharyngeal C. trachomatis in the 7-day treatment was significantly lower than that of cervical C. trachomatis, while there was no significant difference in the 14-day treatment. The eradication rate of pharyngeal C. trachomatis in the 14-day treatment was significantly higher than that in the 7-day treatment. Since the DNA of dead organisms may be detected because of high PCR sensitivity, appropriate therapeutic judgment by PCR could be done around day 22 after completion of the treatment.     

Absorption, distribution, and excretion of [14C]patulin by rats

Adult rats of both sexes were given a single oral dose of [14C] patulin and were sacrificed at various time intervals from 4 hr to 7 days following administration of the mycotoxin. Two groups of rats were employed; the treated group had been exposed to daily oral doses of unlabeled patulin (dissolved in pH 5.0 citrate buffer) in utero and for 41-66 wk after weaning, while the controls were given the buffer only throughout gestation and for 38-81 wk after weaning. Approximately 49% of the administered 14C radioactivity was recovered from feces and 36% from urine within 7 days after dosing. Most of the excretion of labeled material occurred within the first 24 hr. All of the 14C activity detected in the urine samples was either metabolites and/or conjugates of the original [14C]patulin. About 1-2% of the total radioactivity was recovered as 14CO2 from expired air. Carbon-14 radioactivity in various tissues and organs was determined throughout the 7 day period; the most significant retention site was the red blood cells.     

Evaluation of serological tests for the detection of pseudorabies gE antibodies during early infection

Two enzyme-linked immunosorbent assays (ELISAs) and a particle concentration fluorescence immunoassay (PCFIA) were compared for their ability to detect antibodies against pseudorabies virus (Aujeszky's disease virus) glycoprotein E (gE) in the early stages of infection in pigs previously vaccinated with gE-deleted pseudorabies vaccines. Seventy pigs were included in the study. Five groups of 6 pigs each were vaccinated with one of 5 different pseudorabies virus (PRV) gE-deleted vaccines, and subsequently infected intranasally with 10(5.6) TCID50 of the Iowa 4892 pneumotropic strain of PRV. This entire procedure was repeated using 10(4.6) TCID50 of the Rice strain of PRV. Five unvaccinated control pigs were also challenged with each virus strain. Three control pigs died before seroconverting, leaving 67 pigs for comparison. Blood samples were drawn from experimentally inoculated pigs on the day of vaccination, the day of challenge, and on 4-10, 14, and 21 days postchallenge (DPC). Serology test sensitivity estimates and comparisons among tests were made for each sampling day. Results of this study demonstrated differences among the tests in the time from inoculation to initial antibody detection, and the time to detect 50% and 75% of the infected pigs. The average time until first detection of pigs as seropositive for gE antibodies by PCFIA was 7.5 DPC. The blocking ELISA detected pigs as seropositive an average of 8.8 DPC, and the indirect ELISA first detected gE antibodies by 9.3 DPC. Fifty percent of the pigs were detected as seropositive by days 7, 8, and 9 for the PCFIA, blocking ELISA, and indirect ELISA, respectively. Similarly, 75% of the pigs were detected as seropositive by days 8, 9, and 10 for the PCFIA, blocking ELISA, and indirect ELISA, respectively. All pigs were detected as seropositive by 14 DPC for all 3 tests.     

Response of Plasmodium falciparum to chloroquine and Fansidar in vivo and chloroquine and amodiaquine in vitro in Uganda

The response of P. falciparum to chloroquine and pyrimethamine-sulfadoxine in vivo and chloroquine and amodiaquine in vitro was investigated in parasitaemic school children from six locations. Mean parasite sensitivity to chloroquine at day 7 was 74% (range 61-97) with parasite clearance rates between 2-3 days and complete defervescence in 85% of febrile children. Sensitivity declined in the four sites followed up to day 14 to 45% (range 37-53). Parasites were significantly more sensitive to pyrimethamine/sulfadoxine at 5/6 sites (100% day 7) but 5% of subjects became parasitaemic by day 14. In vitro isolates were significantly less sensitive to chloroquine than to amodiaquine with a mean 99% effective concentration of 348 mumol/L compared to 6.44 mumol/L. Clearly the role of chloroquine as the primary therapy for uncomplicated P. falciparum malaria should be reconsidered especially in the light of increasing disease severity and resurgence. Amodiaquine may be suitable alternative with pyrimethamine/sulfadoxine as second line and for more severe malaria prior to referral. The cost of alternative antimalarials and the dynamic and deteriorating pattern of resistance are powerful arguments for more objective slide diagnosis to minimise drug pressure and a regular drug sensitivity surveillance system. We believe that the latter should concentrate on measuring clinical drug efficacy in symptomatic outpatients rather than in asymptomatic children while the former needs more pragmatic and economical strategies possibly centred on seasonality and risk.     

A novel hepatic stellate (Ito) cell-derived protein, epimorphin, plays a key role in the late stages of liver regeneration

Limited data exist regarding morphogenesis and differentiation during liver regeneration. We examined the role of epimorphin on liver regeneration. After 70% partial hepatectomy, mouse liver was collected on days 1, 3, 7, and 14 for immunohistochemistry and the detection of epimorphin mRNA and connexin 32. Using primary cultured rat hepatocytes, morphogenesis and differentiation of cells were tested with or without epimorphin. Seven days after cell inoculation, the expression of connexin 32 and the cell-cell communication was tested as a marker of differentiation. Epimorphin was detected exclusively in hepatic stellate cells. Connexin 32 was detected only in hepatocytes. After partial hepatectomy, epimorphin mRNA was detected on day 3 and peaked at day 7, followed by protein expression. Connexin 32 expression showed a similar time course. Cultured hepatocytes formed multicellular spheroids in an active epimorphin-coated culture dish and showed positive dye coupling, whereas the cell-cell communication was lost without active epimorphin. Because epimorphin was expressed late in liver regeneration, it might play a role in morphogenesis and differentiation.     

Reliability of the Agitated Behavior Scale

Polycyclic aromatic hydrocarbon-DNA adducts were evaluated in oral cells from 98 healthy volunteers by an immunohistochemical method using a specific antiserum against benzo(a)pyrene-DNA adducts revealed by the immunoperoxidase reaction. Mean adduct content, determined as relative staining intensity by absorbance image analyzer, was significantly higher in the cells from tobacco smokers compared with nonsmokers (330 +/- 98, n = 33 versus 286 +/- 83, n = 64, respectively) with a P = 0.013 obtained by two-sample t test with equal variances. We found that in the smoker group, the PAH-DNA adduct content increases with the number of cigarettes. Thus, the relative staining intensity was 305 +/- 105 in the group smoking 1-10 cigarettes/day (n = 16), 347 +/- 77 in the 11-20 group (n = 14), and 386 +/- 112 in the group smoking more than 20 cigarettes/day (n = 3; P = 0.03 by nonparametric test for trend). No significant association was detected between PAH-DNA adducts in oral cells and variables such as residential area, oral infections, alcohol or vitamin intake, grilled food consumption, and professional activity. This work confirms and extends previous data suggesting that this immunohistochemical method might be used as a valuable dosimeter of genotoxic damage in a carcinogen-exposed population, although further studies are needed to verify the applicability of the test in high-risk populations other than smokers.     

Anatomy of schizophrenia revisited

BACKGROUND: The purpose of this study was to investigate whether obliterative bronchiolitis might occur after xenogenic pulmonary transplantation. A model for obliterative airway disease (OAD) after tracheal allograft transplantation in the rat undergoes tracheal obliteration with histologic features characteristic of obliterative bronchiolitis in human lung transplant recipients. Using this model, the pathogenesis of OAD and its prevention with immunosuppressive drugs was studied in rat recipients of hamster tracheal grafts. METHODS: Tracheae from 30 hamsters (xenografts) or 23 Brown-Norway rats (allografts) were implanted and wrapped in the greater omentum of untreated Lewis rats. The grafts were removed on day 1, 3, 7, 14, 21, or 28 after transplantation and stained with hematoxylin and eosin and Masson's trichrome and by immunohistochemistry and immunofluorescence (IFL) techniques. In addition, 25 recipients were treated with cyclosporine (CsA, 10 mg/kg p.o.), leflunomide (LFM, 20 mg/kg p.o.), or rapamycin (RPM, 6 mg/kg i.p.) for 14 or 21 days (5 animals per treatment group). Visual and morphometric analyses were used to evaluate the extent of airway obliteration, luminal coverage by respiratory or flattened cuboidal epithelium, and extent and density of peritracheal cellular inflammation. RESULTS: In all xenografts, a neutrophilic infiltration of the mucosa and submucosa was observed from day 1 until day 14 and was associated with complete loss of tracheal epithelium by day 14. A marked peritracheal mononuclear cellular infiltrate mixed with plasma cells and eosinophils was seen on days 7 and 14. Both the extent of peritracheal inflammation and the density of the mononuclear cell infiltrate were significantly increased in xenograft tracheae when compared with the allografts. Tracheal obliteration began on day 14 and reached a maximum of 43% on day 21 with evidence of intraluminal fibrosis. In contrast to IFL of allografts, IFL of xenografts demonstrated marked deposition of rat immunoglobulin in the peritracheal tissue on days 7 and 14. The effects of treatment with immunosuppressive drugs on tracheal graft narrowing and protection of respiratory epithelium were as follows: After 14 days of treatment, the percentage of tracheal graft narrowing was 12%, 23%, and 19% in the no treatment, CsA, and LFM groups, respectively; the percentage of respiratory epithelium at 14 days was 0%, 21%, and 95%. After 21 days of treatment, the percentage of tracheal graft narrowing was 43%, 49%, 12%, and 5% for the no treatment, CsA, LFM, and RPM groups, respectively; the percentage of respiratory epithelium at 21 days was 0%, 39%, 86%, and 0%. Using computerized morphometry, the extent and densities of the peritracheal cellular infiltrates were significantly reduced in LFM- and CsA-treated groups when compared with untreated xenograft controls. LFM and RPM, but not CsA, significantly reduced the degree of luminal obliteration compared with no treatment (P<0.05). LFM and, to a lesser extent, CsA were able to prevent the loss of normal respiratory epithelium. Analysis by IFL revealed a marked decrease in rat immunoglobulin deposition in xenografts from LFM- and RPM-treated groups compared with xenografts from CsA-treated or untreated rats. CONCLUSIONS: (1) OAD occurs not only after tracheal allotransplantation but also after xenotransplantation. (2) Subepithelial infiltration of neutrophils and the appearance of plasma cells and eosinophils in the peritracheal infiltrates distinguished the histology of rejected xenografts from allografts. (3) Antibody deposition was detected by IFL only in xenografts. (4) Treatment with LFM or RPM significantly decreased the severity of luminal obliteration. Importantly, LFM also prevented the loss of respiratory epithelium.     

Increase in plasma platelet-activating factor levels in enterally fed preterm infants

Because platelet-activating factor (PAF) has been implicated in the pathogenesis of neonatal necrotizing enterocolitis (NEC), we designed a prospective study to examine plasma PAF levels during the first 14 days of feeding in a population of neonates of less than 32 weeks gestation. We found that significantly more patients had detectable plasma PAF levels on days 3 and 14 of feeding when compared to their prefeeding levels (7% on day 0 vs. 26% at day 3, p = 0.04; none on day 0 vs. 18.5% at day 14, p = 0.01). This finding could not be explained by decreased plasma activity of acetylhydrolase, the PAF breakdown enzyme, spontaneous endotoxinemia or a maturational effect. None of the infants who developed detectable PAF levels after feedings were begun went on to develop NEC. We conclude that our findings may reflect increased intestinal PAF production with the provision of feedings to some premature infants. However, this phenomenon by itself does not appear to be a sufficient condition for the subsequent development of NEC.     

Polyamide microcapsules containing alginic acid: extractability of metal ions and surface characterization by XPS

The pathophysiological role of the Thy-1.1 molecule expressed on rat mesangial cells with regard to mesangial cell dysfunction and injury remains unknown. The mechanism of Thy-1.1-associated injury has now been investigated with two monoclonal antibodies, 1-22-3 and OX7, that recognize different epitopes of Thy-1.1. Mesangiolysis and mesangial cell proliferation were more marked in rats injected with 1-22-3 than in those treated with OX7. Immunostaining for rat complement component C3 and also C9 was similar in the kidneys of rats 1 h after injection of either antibody. Alpha smooth muscle actin was first detected 3 days after injection of 1-22-3 and peaked on day 5; type I collagen staining showed a mesangial pattern on days 5 and 10. The staining for alpha smooth muscle actin and type I collagen was less intense in OX7-treated rats than in the 1-22-3-injected rats. The amounts of mRNAs encoding collagen types I and III peaked 5 days after injection of 1-22-3 and 10 days after injection of OX7. Rats injected with 1-22-3 developed proteinuria that was already marked on day 1 and peaked at 150 mg/day on day 3, whereas OX7 induced a low grade of proteinuria with large interindividual variability on day 3. Immunostaining for rat C3 in the normal rat kidneys, incubated in vitro with 1-22-3 or OX7 followed by incubation with normal rat fresh serum as a complement source, as well as the levels of serum complement activity, CH50, 30 min after injection of 1-22-3 or OX7 were similar, suggesting that the difference in the nephritogenicity of these two antibodies is not attributable to a difference in their complement-fixing activities, but rather may result from the difference in epitope specificities. The epitope recognized by 1-22-3 thus appears to be important in the initiation and progression of antibody-induced nephritis.     

Job strain and ambulatory blood pressure among female white-collar workers

To evaluate the nutritional, metabolic and immune effects of dietary arginine, glutamine and omega-3 fatty acids (fish oil) supplementation in immunocompromised patients, we performed a prospective study on the effect of immune formula administered to 11 severe trauma patients (average ISS = 24), 10 burn patients (average % TBSA = 48) and 5 cancer patients. Daily calorie and protein administration were based on the patient's severity (Stress factor with the range of 35-50 kcal/kg/day and 1.5-2.5 g/kg/day, respectively) Starting with half concentration liquid immune formula through nasogastric tube by continuous drip at 30 ml/h and increasing to maximum level within 4 days. The additional energy and protein requirement will be given either by parenteral or oral nutritional support. Various nutritional, metabolic, immunologic and clinical parameters were observed on day 0 (baseline), day 3, 7, and 14. Analysis was performed by paired student-t test. Initial mean serum albumin and transferrin showed mild (trauma) to moderate (burn and cancer) degree of malnutrition. Significant improvement of nutritional parameters was seen at day 7 and 14 in trauma and burn patients. Significant increase of total lymphocyte count (day 7, P < 0.01), CD4 + count (day 7, p < 0.01), CD8 + count (day 7, p < 0.0005 & day 14, p < 0.05), complement C3 (day 7, p < 0.005 day 14, p < 0.01), IgG (day 7, and 14, p < 0.0005), IgA (day 7, p < 0.0005 & day 14, p < 0.05), in all patients. C-reactive protein decreased significantly on day 7 (p < 0.0005) and day 14 (p < 0.005). 3 cases of burn wound infection, one case of UTI and one case of sepsis were observed. Two cases of hyperglycemia in burn, 3 cases of hyperbilirubinemia in trauma, 10 cases of elevated LFT (5 trauma/5 burn), and one case of hyponatremia in cancer patients were observed. Two cases of nausea, 4 cases of vomiting, 5 cases of diarrhea (< 3 times/day), 2 cases of abdominal cramp, 1 case of distension were observed. The feeding of IMMUNE FORMULA was well tolerated and significant improvement was observed in nutritional and immunologic parameters as in other immunoenhancing diets. Further clinical trials of prospective double-blind randomized design are necessary to address the so that the necessity of using immunonutrition in critically ill patients will be clarified.     

Efficacy of antimicrobial treatment in non-dysenteric persistent diarrhoea in a community setting

OBJECTIVES: To determine the efficacy of antimicrobial treatment in non-dysenteric persistent diarrhoea in a community setting. METHODS: In this double-blind field trial, 156 children aged 4-36 months with persistent diarrhoea not associated with Giardia lamblia infestation seeking treatment in a community outpatient clinic, were randomized to receive a combination of nalidixic acid and metronidazole, metronidazole alone, or placebo for 7 days. RESULTS: In comparison with placebo, metronidazole treatment did not result in a significant reduction in the mean post-enrollment diarrhoeal duration and stool frequency, increase in the proportion of patients recovered by days 3, 5 and 7 of treatment, and increase in weight gain at days 7 and 14. Comparing the combination of nalidixic acid and metronidazole with metronidazole alone, 17.5% more children treated with the combination recovered by day 3 of treatment (p = 0.08) and the mean stool frequency ascertained on day 7 for the previous 24 h was 26.8% less in them (p = 0.05). The weight gains at days 7 and 14 were similar in the two groups. CONCLUSIONS: These findings indicate that metronidazole offers no therapeutic benefit in persistent diarrhoea not associated with Giardia lamblia and nalidixic acid has only a modest clinical benefit, which is not substantial enough to warrant its routine use.     

Microbial inhibitory properties and stability of topotecan hydrochloride injection

The viability of five microorganisms in topotecan 1 mg/mL (as the hydrochloride salt) in sterile water and the stability of the drug were studied. Duplicate portions of topotecan 1 mg/mL were inoculated with Escherichia coli. The process was repeated for Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, and Aspergillus niger. Samples were removed from each solution initially and after 6, 16, and 24 hours and 3, 7, 14, 21, and 28 days of incubation at 20-25 degrees C. To test stability, vials of reconstituted topotecan hydrochloride injection were stored at each of three temperatures--5, 25, and 30 degrees C--and other vials were used for time zero analysis. For each temperature, vials were removed at 1, 7, and 14 days and the remaining vials at 28 days for analysis by high-performance liquid chromatography and for visual and pH assessment. P. aeruginosa, S. aureus, and E. coli lost viability at 16 hours, 24 hours, and 28 days, respectively. C. albicans and A. niger did not lose viability, but their numbers did not grow. No differences in color or clarity were observed, and pH was constant. In all solutions, the topotecan concentration was > 98% of the initial concentration. Topotecan 1 mg/mL in sterile water stored at 20-25 degrees C for up t 28 days did not support growth of the five microorganisms studied; in solutions stored at 5, 25, or 30 degrees C for up to 28 days, topotecan 1 mg/mL remained stable.     

Midline interhemispheric fusion associated with atypical callosal dysgenesis: a mild type of holoprosencephaly

Pubertal male Wistar rats were submitted to bilateral castration and killed 7 or 14 days later; an additional group of castrated rats was submitted to ultrasound stimulation of the ventral region lying above the accessory sex glands, for 20 min a day from the 7th to the 14th day postcastration. Control intact rats were age-matched to the different treated groups. Seminal vesicle growth and secretory activity were investigated on the basis of weight and fructose content, respectively. A progressive fall in seminal vesicle weight was observed over a period of 7 (83% decrease) to 14 (92% decrease) days following castration; ultrasound treatment beginning on the 7th day prevented this additional weight reduction. Castration caused also a marked decrease (50-60%) in the fructose content of the seminal vesicle and the ultrasound energy promoted a partial recovery of the secretory activity of the gland. The results revealed a direct ultrasound stimulation of the seminal vesicle secretory activity in pubertal rats deprived of testicular androgens.