The Effect of Metformin and Standard Therapy versus Standard Therapy alone in Nondiabetic Patients with Insulin Resistance and Nonalcoholic Steatohepatitis (NASH): A Pilot Trial.

Nonalcoholic steatohepatitis (NASH) is increasing in prevalence and is related to underlying insulin resistance. The aim of this study was to assess the efficacy of metformin on the characteristic histopathologic lesions of NASH. This was a 12-month prospective, randomized, placebo-controlled trial comparing diet and exercise alone to diet, exercise and metformin in nondiabetic patients with insulin resistance and NASH. Patients were randomized to either group A or B. Group A received placebo, dietary counseling, recommendations for weight loss and exercise four times per week. Group B received long-acting metformin 500 mg daily (titrated to 1000 mg daily) plus dietary counseling, recommendations for weight loss and exercise four times per week. Histopathology was assessed at 12 months and biopsies were scored by two pathologists who were blinded to all data. Twenty-three subjects were screened and 19 were randomized to either group A (n »10) or group B (n» 9). Seven of the 10 subjects in group A completed the study including repeat liver biopsy while all patients in group B completed the study. Body mass index improved in both groups decreasing by 1.7 kg/m(2) in group A and 0.9 kg/m(2) in group B (not significant, control versus treatment). Homeostasis model assessment of insulin resistance scores improved in both groups decreasing by 1.14 in group A and 1.58 in group B (not significant, control versus treatment). No significant difference in histopathology was seen between groups on follow-up liver biopsy. Metformin appeared to have little effect in improvement in liver function tests or liver histology in nondiabetic patients with insulin resistance and NASH. Decrease in BMI through diet and exercise significantly improved HOMA-IR scores, serum aminotransferases and liver histology.

A numerical study on the coalescence of emulsion droplets in a constricted capillary tube.

Using a new computational model, we have studied the dynamics and coalescence of a pair of two-dimensional droplets in pressure-driven flow through a constricted capillary tube, which is a prototype problem for the analysis of the interaction of emulsion droplets in porous media. We present simulations that quantify the effects of various system parameters on the droplet stability. These include the capillary number, the interfacial tension, the suspended-to-suspending-phase viscosity ratio, the valence and concentration of added electrolytes, the droplet-to-pore-size ratio, the pore-body-to-throat-size ratio, and the type of pore geometry. Our simulations show that the capillary number Ca plays an important role in determining whether the drops coalesce. At low Ca, drops deform only slightly and coalescence occurs at the entrance of the pore throat, whereas significant deformation enables the drops move through the pore without coalescence at high Ca. Coalescence is favored at intermediate values of the viscosity ratio. The destabilizing effect of added electrolytes is found to be insignificant for 10-mum drops, but significant for micron-size drops. Among the geometric-related parameters, the drop-to-pore-size ratio is the most significant.

Apoptosis induced in rats by 4-vinylcyclohexene diepoxide is associated with activation of the caspase cascades.

Previous studies have shown that ovotoxicity induced in rats by dosing with 4-vinylcyclohexene diepoxide (VCD) is likely via acceleration of the normal rate of atresia (apoptosis). The present study was designed to investigate the apoptosis-related caspase cascades as a component of this phenomenon in isolated ovarian small follicles. Female F344 rats were given a single dose of VCD (80 mg/kg, i.p., on Day 1; a time when ovotoxicity has not been initiated), or dosed daily for 15 days (80 mg/kg, i.p., on Day 15; a time when significant ovotoxicity is underway). Ovaries were collected after the final dose. Small preantral follicles (25-100 microm in diameter) were isolated, cellular fractions were prepared, and cleavage activity or protein expression levels of caspases-3, -8, and -9 were measured. Cytosolic caspase-3 activity was increased in small follicles (P < 0.01) by VCD treatment (Day 1, 2.86 +/- 0.23; Day 15, 3.25 +/- 0.64, VCD/control, n = 3). This activation was not seen in large or antral follicles (not targeted by VCD). Procaspase-3 protein was increased(P < 0.05) by VCD treatment 212% over controls in small ovarian follicles in Day 15, but not Day 1-dosed rats. Immunofluorescence staining intensity was evaluated by confocal microscopy. Caspase-3 protein, located in the cytosolic compartment of oocytes and granulosa cells of preantral follicles in various stages of development, was selectively increased (P < 0.05) in primordial and small primary follicles from Day 15 VCD-dosed rats. Caspase-8 activity was increased in small follicles in Day 15, but not in Day 1-treated rats; whereas caspase-9 activity was increased by VCD on Day 1 in the mitochondrial fraction. Thus, these data provide evidence that accelerated atresia induced in small ovarian follicles in rats by VCD is associated with activation of a caspase-mediated cascade.

Ovarian toxicity of 4-vinylcyclohexene diepoxide: a mechanistic model.

Female mammals are born with a finite number of ovarian primordial follicles that cannot be regenerated; thus, chemicals that destroy oocytes contained in these follicles can produce premature ovarian failure (early menopuase in women). Exposure of women to known ovotoxicants, such as contaminants in cigarette smoke, is associated with early menopause. Thus, the potential risks posed by ovotoxic chemicals is of concern. Our studies have focused on the environmental chemical 4-vinylcyclohexene (VCH), which is produced during the manufacture of rubber tires, flame retardants, insecticides, plasticizers, and antioxidants. Dosing of female rats and mice with the ovotoxic diepoxide metabolite of VCH, 4-vinylcyclohexene diepoxide (VCD), for 30 days destroyed the majority of ovarian primordial follicles. Using VCD in rats as a generalized model for ovotoxicity, we determined that 1) repeated daily dosing is required, 2) cell death is via apoptosis, and 3) altered expression of specific genes is involved. An integrated approach at the morphologic, biochemical, and molecular level was used to support these conclusions. Studies in isolated rat small preantral follicles (targeted for VCD-induced ovotoxicity) focused on the role of cell death genes, mitochondrion-associated events, and VCD metabolism. We also evaluated how this information relates to human risk for early menopause. These animal research results provide a better understanding of the potential risk of human exposure to environmental ovarian toxicants and greater insight as to the impact of these toxicants on reproductive health in women.

Synchronizing estrus and(or) ovulation in beef cows after combinations of GnRH, norgestomet, and prostaglandin F2alpha with or without timed insemination.

Three experiments were conducted to induce estrus and(or) ovulation in 1,590 suckled beef cows at the beginning of a spring breeding season. In Exp. 1, 890 cows at three locations were allotted to three treatments: 1) GnRH on d -7 + prostaglandin F2alpha (PGF2alpha) on d 0 (Select Synch); 2) GnRH on d -7 + PGF2alpha on d 0 (first day of the breeding season) plus a norgestomet implant (NORG) between d -7 and 0 (Select Synch + NORG); or 3) two injections of PGF2alpha given 14 d apart (2xPGF2alpha). More (P < 0.05) cycling cows were detected to have been in estrus after both treatments that included GnRH, whereas, among noncycling cows, the addition of norgestomet further increased (P < 0.05) the proportion in estrus. Pregnancy rates were greater (P < 0.01) among noncycling cows after treatments that included GnRH. For cows that calved >60 d before the onset of the breeding season, conception rates were greater (P < 0.01) than those that calved < or =60 d regardless of treatment, whereas days postpartum had no effect on rates of detected estrus. When body condition scores were < or =4 compared with >4, rates of detected estrus (P < 0.05) and conception (P = 0.07) were increased. In Exp. 2, 164 cows were treated with the Select Synch + NORG treatment and were inseminated either after estrus or at 16 h after a second GnRH injection (given 48 h after PGF2alpha). Conception and pregnancy rates tended (P = 0.08) to be or were less (P < 0.05), respectively, for noncycling cows inseminated by appointment, but pregnancy rates exceeded 53% in both protocols. In Exp. 3, 536 cows at three locations were treated with the Select Synch protocol as in Exp. 1 and inseminated either: 1) after detected estrus (Select Synch); 2) at 54 h after PGF2alpha when a second GnRH injection also was administered (Cosynch); or 3) after detected estrus until 54 h, or in the absence of estrus, at 54 h plus a second GnRH injection (Select Synch + Cosynch). Conception rates were reduced (P < 0.01) in cows that were inseminated by appointment. An interaction of AI protocol and cycling status occurred (P = 0.05) for pregnancy rates with differing results for cycling and noncycling cows. Across experiments, variable proportions of cows at various locations (21 to 78%) were cycling before the breeding season. With the GnRH or GnRH + NORG treatments, ovulation was induced in some noncycling cows. Conception rates were normal and pregnancy rates were greater than those after a PGF2alpha program, particularly when inseminations occurred after detected estrus.

Follicular, hormonal, and pregnancy responses of early postpartum suckled beef cows to GnRH, norgestomet, and prostaglandin F2alpha.

Cycling (n = 16) and noncycling (n = 24), early postpartum, suckled beef cows of three breeds were assigned randomly to three treatments: 1) 100-microg injection of GnRH plus a 6-mg implant of norgestomet administered on d -7 before 25 mg of PGF2alpha and implant removal on d 0 (GnRH+NORG); 2) 100 microg of GnRH given on d -7 followed by 25 mg of PGF2alpha on d 0 (GnRH); or 3) 2 mL of saline plus a 6-mg implant of norgestomet administered on d -7 followed by 25 mg of PGF2, and implant removal on d 0 (NORG). All cows were given 100 microg of GnRH on d +2 (48 h after PGF2alpha). Blood sera collected daily from d -7 to d +4 were analyzed for progesterone and estradiol-17beta, and ovaries were monitored daily by transrectal ultrasonography to assess changes in ovarian structures. Luteal structures were induced in 75% of noncycling cows in both treatments after GnRH, resulting in elevated (P < .01) progesterone on d 0 for GnRH+NORG-treated cows. Concentrations of estradiol-17beta (P < .01) and LH (P < .05) were greater on d +2 after GnRH for cows previously receiving norgestomet implants. Pregnancy rates after one fixed-time AI at 16 h after GnRH (d +2) were greater (P < .05) in GnRH+NORG (71%) than in GnRH (31%) and NORG (15%) cows. Difference in pregnancy rate was due partly to normal luteal activity after AI in over 87% of GnRH+NORG cows and no incidence of short luteal phases. The GnRH+NORG treatment initially induced ovulation or turnover of the largest follicle, induction of a new follicular wave, followed later by increased concentrations of estradiol-17beta and progesterone. After PGF2alpha, greater GnRH-induced release of LH occurred in GnRH+NORG cows before ovulation, and pregnancy rates were greater after a fixed-time AI.

A single dose of the ovotoxicant 4-vinylcyclohexene diepoxide is protective in rat primary ovarian follicles.

Repeated dosing of rats with the ovotoxic chemical, 4-vinylcyclohexene diepoxide (VCD), destroys primordial and primary ovarian follicles via apoptosis (physiological cell death) by accelerating the normal rate of atresia. The present study investigated the effect of a single dose (1x) of VCD. Immature (d28) female Fischer 344 rats were dosed 1x or 15x with VCD (80 mg/kg ip). Ovaries were collected 24 h or 15 days following 1x VCD or after 15x for classification and evaluation. Following 1x VCD the number of healthy primary follicles was greater (p < 0.05) than control 24 h and 15 days later. This effect reflected a slowing of the normal rate of atresia seen in control ovaries. There was no effect of a single dose on primordial or growing follicles at any time. Expression of mRNA encoding the cell death gene bax was reduced (p < 0.05) on d1 after 1x VCD in isolated primordial and primary follicles. These observations were in contrast to a decreased (p < 0. 05) number of healthy primary and primordial follicles in ovaries and increased (p < 0.05) bax mRNA in isolated follicles from rats dosed 15x for 15 days. Immunofluorescence staining revealed that, the distribution of Bax protein was similar between ovaries from controls and 1x or 15x VCD-treated rats. These data provide evidence for a "protective" response against the normal rate of atresia in primary ovarian follicles following exposure to 1x VCD. Additionally, changes in expression of bax mRNA paralleled alterations in the rate of atresia.

Twice daily suckling but not milking with calf presence prolongs postpartum anovulation.

Two experiments were conducted to determine whether milking beef cows two or five times daily in the presence or absence of their own nonsuckling calves would alter postpartum interval to first ovulation. Multiparous Angus x Hereford cow-calf pairs were assigned randomly between 13 and 18 d postpartum to treatments for 4 wk. In Exp. 1, pairs were assigned to six treatments: 1) calf was weaned permanently from its dam (CW; n = 9); 2) same as CW, but dam was milked twice daily (CW+2xM; n = 9); 3) calf was present continuously with its dam but restricted from contact with the udder (CR; n = 9); 4) same as CR, but dam was milked twice daily (CR+2xM; n = 9); 5) same as CR, but calf was allowed to suckle twice daily (CR+2xS; n = 8); and 6) calf was present continuously with its dam and suckled ad libitum (CP; n = 9). The interval from onset of treatments to first postpartum ovulation was shorter (P<.05) in the CW (14.1+/-3.1 d), CR (14.2+/-3.1 d), CW+2xM (13.0+/-3.1 d), and CR+2xM (17.2+/-3.1 d) than in the CP (34.7+/-3.1 d) and CR+2xS (33.9+/-3.3 d) treatments. Daily milk yield during treatment was greater (P<.01) for CR+2xM cows (7.1+/-.6 kg) than for CW+2xM cows (3.5+/-.6 kg). In Exp. 2, cow-calf pairs were assigned to three treatments: 1) CR+2xM (n = 10); 2) same as CR+2xM but cows were milked five times daily (CR+5xM; n = 10); or 3) CP (n = 10). The interval to first postpartum ovulation was shorter (P<.05) in the CR+2xM (23.6+/-3.5 d) and CR+5xM (26.1+/-3.7 d) treatments than in the CP (37.7+/-3.7 d) treatment. Daily milk yield during treatment was greater (P<.05) for CR+5xM cows (7.7+/-.6 kg) than for CR+2xM cows (6.4+/-.6 kg) by 17%. We conclude that suckling twice daily was sufficient to prolong postpartum anestrus as much as suckling ad libitum. Furthermore, milk removal by suckling, but not by milking two or five times daily, even in the presence of the cow's own nonsuckling calf, is essential to prolong postpartum anovulation.

Reproductive performance of dairy cows in various programmed breeding systems including OvSynch and combinations of gonadotropin-releasing hormone and prostaglandin F2 alpha.

In Experiment 1, 308 Holstein cows were assigned randomly to four treatments: 1) GnRH injection followed in 7 d by PGF2 alpha injection, then another GnRH injection 33 h later, and artificial insemination (AI) 16 to 18 h after the second GnRH injection; 2) GnRH injection followed in 7 d by PGF2 alpha injection and AI only after detected estrus; 3) injections of PGF2 alpha 14 d apart, GnRH injection 33 h after the second PGF2 alpha injection, and AI 16 to 18 h later; and 4) injections of PGF2 alpha 14 d apart, AI only after detected estrus following the second PGF2 alpha injection or, in the absence of detected estrus, at 80 h after the second PGF2 alpha injection. In Experiment 2, 227 Holstein cows were assigned randomly to two treatments: 1) GnRH injection followed in 7 d by PGF2 alpha injection, then another GnRH injection 48 h later, and AI 16 to 18 h after the second GnRH injection; and 2) GnRH injection followed in 7 d by PGF2 alpha injection and AI only after detected estrus. Although conception rates in both experiments resulting from AI made after detected estrus either tended to be greater or were consistently greater than those following GnRH injection and one fixed-time AI, pregnancy rates were of greater magnitude after fixed-time AI because of poor expression or detection of estrus.

Modelling the internalization of labelled cells in tumour spheroids.

In this paper a mathematical model is developed to describe the migration of labelled particles within a multicell spheroid. In the model, spatial variations in cell proliferation and death create an internal velocity field which leads to redistribution of the labelled and unlabelled cells. By applying a range of numerical and analytical techniques to the model equations, it is possible to show that, whilst the speed with which the labelled cells migrate through the tumour is independent of the type of cells that are labelled, their limiting distribution depends crucially on whether inert polystyrene microspheres or live tumour cells are labelled. These predictions are shown to be in good qualitative agreement with independent experimental results.

Hypoxia and reoxygenation: a pressure for mutant p53 cell selection and tumour progression.

Recent findings indicate that in a hypoxic environment, oncogenically transformed cells with a mutant form of the tumour suppressor gene p53 may have a survival advantage over similar cells with wild-type p53. This is because the extent of hypoxia-induced apoptosis has been observed to diminish with the loss of wild-type p53 function in certain cell lines. Hypoxic conditions, common in most solid tumours, may thus provide a physiological pressure to select for cells with mutations in the p53 gene. A new model incorporating cell-specific parameters is proposed here to quantify the survival advantage of mutant or null p53 cells over their wild-type counterparts at any level of oxygen deprivation. Predictions are in good agreement with previous monolayer culture experiments comparing hypoxic survival of null and wild-type p53 cells. By extending the model we are able to investigate the effects of repeated rounds of hypoxia and reoxygenation on a mixture of wild-type and mutant or null p53 cells and determine how many rounds are required before a subpopulation of mutant or null p53 cells overtakes a given population of wild-type p53 cells.

AML1-like transcription factor induces serine elastase activity in ovine pulmonary artery smooth muscle cells.

In previous studies, we showed that induction of pulmonary artery (PA) smooth muscle cell (SMC) elastase activity by serum-treated elastin (STE) requires DNA transcription. We therefore used differential mRNA display to identify transcripts expressed coincident with elastase induction. Twenty-four individual transcripts were differentially expressed from a screen of approximately 2000 mRNA sequences. An mRNA with sequence homology to the human transcription factor AML1 was identified and subsequently cloned from ovine PA SMCs. Since AML1 binds to a consensus sequence in the promoter of neutrophil elastase, we pursued the possibility that AML1 is a candidate transcription factor for SMC elastase. We documented by immunohistochemistry that serum stimulation induces increased expression of AML1 in the nucleus of PA SMCs. We also showed that STE induction of elastase activity is associated with early expression of AML1 mRNA and protein and that AML1 consensus sequence DNA binding activity is increased in nuclear extracts of STE-treated cells. In addition, AML1 antisense oligonucleotides reduced serum induction of elastase activity. Our study thus provides the first functional evidence of AML1 transcriptional activity related to elastase genes and offers novel insights into the broader biological significance of AML1 in nonmyeloid cells.

Specific detection of shedding and latency of bovine herpesvirus 1 and 5 using a nested polymerase chain reaction.

A sensitive method for simultaneously detecting and discriminating between bovine herpesviruses types 1 and 5 (BHV-1 and BHV-5) was developed using a nested polymerase chain reaction (PCR) technique. Following amplification using type-common primers derived from gC sequences, amplification using type-specific nesting primers produced different-sized bands specific to the corresponding types, as demonstrated by blot hybridization. Less than 0.1 plaque-forming units (PFU) of each virus and 75 fg or less of viral DNA were routinely detected. The PCR technique amplified correct product from 4 BHV-5 isolates and from 48 BHV-1 isolates, all from the United States, and did not amplify heterologous herpesviruses. The PCR technique was more sensitive than virus isolation in detection of BHV-1 or BHV-5 in nasal secretions from experimentally and naturally infected calves, and it detected BHV-1 or BHV-5 in trigeminal ganglia from these calves.

Blunted cardiovascular growth induction during prolonged nitric oxide synthase blockade.

The goal of the present study was to characterize the activation profile of the growth-related enzyme ornithine decarboxylase (ODC) in cardiovascular tissue during hypertension induced by chronic NO synthase blockade in relation to the development of structurally based changes in the heart and blood vessels. In previously instrumented conscious rats, mean arterial pressure and ODC activation were measured in cardiovascular tissue of rats treated with N(omega)-nitro-L-arginine methyl ester (L-NAME; 100 mg/kg per day P.O.) for 4 hours and 1, 6, and 12 days. After 12 days of L-NAME treatment alone or in combination with 3% L-ornithine, structurally based hindlimb resistance properties were assessed. A marginal activation of ODC in the left ventricle and aorta was seen at 4 hours but returned to control levels at 1, 6, and 12 days of L-NAME treatment. A slightly prolonged yet transient activation of ODC occurred in the mesenteric vascular bed. Structurally based hindlimb vascular resistance was enhanced by 15% at maximum vasoconstrictor tone, and no change in cardiac mass occurred with L-NAME treatment. L-NAME+3% L-ornithine treatment resulted in a similar level of structural upregulation compared with L-NAME treatment alone. In summary, 12 days of L-NAME treatment resulted in only a modest change in vascular resistance, and only at maximum constriction, and no cardiac hypertrophy despite the presence of marked hypertension. The results of the present study indicate that either (1) pressure alone is not a sufficient stimulus to induce cardiovascular growth processes or (2) L-NAME may be "nonspecifically" inhibiting cardiovascular growth processes.

Evidence in vivo for induction of cardiovascular growth processes by vasoconstrictor systems.

Greater smooth muscle growth is an important feature of the changes in blood vessel morphology in hypertension. The increase in vessel wall thickness: lumen ratio resulting from vascular hypertrophy impacts directly on total peripheral vascular resistance thereby influencing the severity of hypertension. The roles played by mechanical forces, vasoactive substances, growth factors and endocrine hormones in mediating hypertrophic vascular growth responses in vivo are currently under investigation. Here we review our current research aimed at: (a) defining the roles in vivo, of the renin-angiotensin system (RAS) and sympathetic nervous system (SNS), in the development of cardiovascular hypertrophy; (b) defining the importance of endogenous vasodilator systems, in particular, the ability of nitric oxide to inhibit trophic responses induced by the RAS and SNS and (c) examining whether trophic stimulation via the two neurohumoral systems as well as the antitrophic activity of the vasodilator systems is in part dependent on changes in blood pressure. In these studies the obligatory enzyme ornithine decarboxylase has proved to be a useful marker of ongoing hypertrophic cardiovascular growth.

Differential effect of short-term ethanol on cardiac and vascular growth responses.

OBJECTIVE: To determine in rats the acute effect of ethanol on the activity of a marker of cardiac and vascular growth processes (ornithine decarboxylase) and on alpha 1-adrenergic-induced vascular trophic responses, and whether ethanol-induced sympathoadrenal hyperactivity stimulated vascular structural changes after a more prolonged treatment. METHODS: Acute treatment was as follows: ethanol (5 g/kg, intubation), alpha 1-adrenergic agonist (10 mg/kg methoxamine subcutaneously), methoxamine plus ethanol, or control. Left ventricular, aortic and mesenteric vascular ornithine decarboxylase activity was determined 4 h later by measuring 14CO2 evolved from [14C]-ornithine. Three-day treatment was as follows: ethanol (every 8 h, intubation, 5 g/kg initial dose, subsequent doses based on intoxication level) or isocaloric quantities of maltose dextrin. The left ventricular: body weight ratio, hindlimb vascular resistance properties and indices of cardiac and vascular hypertrophy were determined. RESULTS: In the acute treatment methoxamine-induced pressor responses and the activation of vascular ornithine decarboxylase were both inhibited by ethanol treatment. Ethanol alone elevated the heart rate and decreased mean arterial pressure while stimulating left ventricular but not vascular ornithine decarboxylase activity. Methoxamine did not alter left ventricular ornithine decarboxylase activity. Three-day ethanol treatment induced cardiac hypertrophy but had no effect on the hindlimb vascular resistance properties measured at maximum dilation and maximum constriction. CONCLUSIONS: Acute and short-term ethanol exposure induces cardiac growth processes. Ethanol prevents alpha 1-adrenergic activated vascular growth response by a mechanism that may be similar to the attenuation of alpha 1-adrenergic-induced elevation of arterial pressure.

Vasodilators inhibit acute alpha 1-adrenergic receptor-induced trophic responses in the vasculature.

Cardiovascular hypertrophy plays an important role in the development and maintenance of hypertension. Hyperactivity of the sympathetic nervous system may be one of the initiating factors responsible for the stimulation of growth processes involved in these structural alterations. We have used a well-established early biochemical marker of cellular growth processes, induction of ornithine decarboxylase (ODC), to determine whether alpha 1-adrenergic receptor-induced vascular trophic responses are dependent on arterial pressure elevation. Hydralazine or felodipine were coadministered to control the alpha 1-adrenergic receptor agonist-induced rise in mean arterial pressure (MAP). Methoxamine (2, 5, or 10 mg/kg s.c.) increased the average MAP (up to 20 mm Hg) and vascular ODC activity (up to ninefold) above control rats over 4 hours. Concomitant administration of hydralazine (0.5, 1.25, or 5 mg/kg s.c.) or felodipine (100 or 250 micrograms/kg s.c.) with methoxamine (10 mg/kg) attenuated the alpha 1-adrenergic receptor-induced activation of ODC in the aorta and mesenteric resistance vasculature, as well as the MAP increases. Vasodilators alone did not lower basal vascular ODC activity. The major findings include: 1) alpha 1-adrenergic receptor activation dose-dependently induces vascular ODC activity concomitantly with MAP elevation, 2) vasodilators inhibited both the alpha 1-adrenergic receptor-induced MAP increases and the activation of mesenteric vascular and aortic ODC, and 3) the stimulus-response correlation between MAP elevation and mesenteric (r = 0.78) and aortic (r = 0.92) ODC activation was characterized by a logistic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Transabdominal chorionic villus sampling for rapid karyotyping in advanced gestation.

Late pregnancy fetal karyotyping is not employed often because a clinical decision about labor and delivery may be required before the results would be available. However, percutaneous umbilical blood sampling (PUBS) has been used recently to obtain fast karyotypes. We have extended our chorionic villus sampling (CVS) procedure to the second and third trimesters and compared the results obtained with late CVS and PUBS. CVS karyotypes were obtained faster and may be technically easier to perform.