Luminal Volume Research Articles

Evidence That Estrogens Directly Alter Androgen-Regulated Prostate Development*

Neonatal exposure to high doses of estrogen results in permanent suppression of prostate growth and reduced sensitivity to androgens in adulthood. It is unclear whether alterations in prostate growth are due to a direct effect of estrogens on the gland or are the result of hypothalamic-pituitary-gonadal axis suppression and a subsequent reduction in androgen levels. Therefore, the aim of this study was to determine whether estrogens have a direct effect on the prostate using a defined method of culturing neonatal prostates. Newborn rat ventral prostates were microdissected and cultured in the presence of testosterone, which resulted in branching morphogenesis and ductal canalization. Solid cords of epithelium differentiated into acini lined by tall columnar epithelial cells; these acini were surrounded by stromal cells, expressing smooth muscle alpha-actin. When cultured in the presence of 17beta-estradiol or diethylstilbestrol in addition to testosterone, androgen-induced prostatic growth was reduced, and differentiation was altered. Although estrogen-treated explants were smaller than controls, quantification of epithelial, stromal, and luminal volumes using unbiased stereology revealed significant changes; the proportion of epithelial cells and lumen decreased, and the proportion of stroma increased compared with control values. Concurrent with this reduced growth rate, we observed a disturbance in the branching pattern and a reduction in ductal canalization. Specifically, stromal differentiation and organization were disrupted, so that a discontinuous smooth muscle layer was observed around the epithelial ducts, and epithelial differentiation was altered. The effects of estrogens were not accompanied by a decrease in androgen response via the androgen receptor, because immunolocalization of this receptor remained constant. These data demonstrate that high doses of estrogens are growth inhibitory and have direct effects on prostate development in vitro, which may occur in vivo in addition to indirect effects via suppression of the hypothalamic-pituitary-gonadal axis.

Luminal osmolarity downregulates gene expression of Na +/H + exchanger (NHE3) in rat colon mucosa

Water-coupled Na + absorption in the colon is mediated principally by Na +/H + exchange (isoforms NHE2 and NHE3). To determine whether luminal ion composition or osmolarity influences NHE expression in colon mucosa, two groups (n = 6 in each) of adult male Sprague-Dawley rats underwent sham laparotomy or loop ileostomy. In these studies, diversion did not markedly alter mRNA levels for NHE2, NHE3, or Na +/K +, at 8 or 21 days, indicating that loss of luminal volume does not alter NHE gene expression. To evaluate the effects of specific luminal components, we infused equal volumes of half-normal (154 mOsm) or iso-osmolar (308 mOsm) solutions of saline and mannitol into the diverted colon. All solutions elicited significant (45% to 60%; P <0.05) decreases in mRNA levels for NHE3, with iso-osmolar mannitol eliciting the greatest changes. Decreases in NHE2 and Na +/K + mRNA levels were observed following these infusions but were not as marked as the changes for NHE3. These findings suggest that (1) loss of luminal Na + is not, in itself, a signal that regulates NHE expression and (2) infusion of any solute, including Na + itself, provides a signal to downregulate expression of NHE3 in colon mucosa.

Multidimensional assessment of graft vascular disease (GVD) in aortic grafts by serial intravascular ultrasound in rhesus monkeys.

Graft vascular disease (GVD) is an incompletely understood process and the primary cause of late allograft failure. A nonhuman primate model was established to study the progression of GVD by using serial intravascular ultrasound (IVUS). Aortic allografts were transplanted below the inferior mesenteric arteries (IMA) into 6 rhesus monkeys. Removed and re-implanted aortic segments between renal arteries, and the inferior mesenteric arteries served as autografts. IVUS was performed at days 0, 24, 52, 80, and 98 after transplantation. Vessel area (VA) and lumen area (LA) were measured from each cross-section at 0.5 mm intervals. Intimal index (II=100x (VA-LA/VA)) and corresponding vessel volumes were calculated for the whole grafts. Histologic features were assessed from autopsy samples using computerized morphometric method and a score from 0 to 3 for GVD (0=none, 3=severe). In allografts, vessel volume and luminal volume decreased significantly (P<0.05 for both) and the intimal index increased from 12% to 59% by day 98. These parameters remained unchanged in autografts. Histologic analysis of allografts showed concentric intimal hyperplasia and scattered mononuclear cell accumulations, whereas the autografts had only occasional eccentric intimal changes. The GVD-scores were significantly higher in allografts than in autografts (median 3 vs. 1, P=0.042). We introduce a nonhuman primate model of GVD that enables serial IVUS assessments of multiple parameters of GVD. Concentric intimal proliferation and decrease of vessel dimensions was observed in allografts as a consequence of alloimmunity. This is a potential new model for studying new therapies to prevent GVD or halt its progression.

Testicular heat exposure enhances the suppression of spermatogenesis by testosterone in rats: the "two-hit" approach to male contraceptive development.

The objectives of the study were to determine stage-specific changes in the kinetics of germ cell apoptosis induced by administration of exogenous testosterone (T) alone and to examine whether addition of a single testicular heat exposure would enhance the induction of germ cell apoptosis and the suppression of spermatogenesis by T. Adult male rats were implanted with 3-cm SILASTIC brand capsules (Dow Corning Corp.) containing T for up to 6 weeks. Intratesticular T levels declined to 2.9% of control values by 1 week and remained suppressed at 2, 3, and 6 weeks after T administration. The incidence of germ cell apoptosis (expressed as numbers per 100 Sertoli cells) was low in control rats (0-9.52). After T treatment, the mean incidence of apoptosis at stages VII-VIII increased significantly by 1 week (21.43 +/-3.33) and showed further increases by 6 weeks (56.30 +/- 7.47); apoptotic rates remained low at early (I-VI) and later (XII-XIV) stages. To test whether the combination of T with a single testicular heat exposure resulted in more complete suppression of spermatogenesis than either treatment alone, four groups of adult rats received one of the following treatments: 1) a subdermal empty polydimethylsilozane implant, 2) exposure to a single testicular heating (43 C for 15 min) applied on day 14, 3) 3-cm T implant, or 4) 3-cm T implant and a single testicular heat exposure (applied on day 14). All animals were killed at the end of 6 weeks. In the heat-treated group, testis weight and testicular sperm counts were decreased to 65.4% and 28.9% of control levels, respectively. The corresponding values in the T-treated group were 49.7% and 24.9% of control levels, respectively. Notably, addition of heat to T further reduced testis weight to 31.1% of control levels and testicular sperm counts to near zero. Histomorphometric analysis showed that all treatments reduced seminiferous tubular diameter and epithelial and luminal volume, with the greatest decrease after combined T and heat treatment. Heat exposure in animals bearing T implants markedly reduced the number of pachytene spermatocytes and round spermatids through apoptosis, resulting in tubules devoid of mature spermatids. Spermatogonia and preleptotene spermatocytes remained unaffected. These results clearly demonstrate that 1) exogenous T reduces intratesticular T and induces apoptosis mainly at stages VII-VIII within 1-6 weeks; 2) the combined treatment of T and heat markedly inhibits spermatogenesis, resulting in near azoospermia within 6 weeks; and 3) meiosis and spermiogenesis are the most vulnerable phases of spermatogenesis in response to T plus heat treatment. These findings suggest that a combination of hormonal treatment such as T and a physical agent (heat exposure) is more effective in suppressing spermatogenesis than either treatment alone. We hypothesize that combination of two antispermatogenic agents ("two hit") working at separate stages of the spermatogenic cycle will lead to greater male contraceptive efficacy.

A stop-flow microperfusion technique for rapid determination of HCO3- absorption/H+ secretion by isolated renal tubules.

In the present experiments on microdissected tubules of rabbit kidney we present a refined stop-flow method for determining the rate of HCO3- absorption (J(HCO3)) or H+ secretion (JH) that can be applied to isolated microperfused tubules. Using the pH-sensitive indicator dye BCECF (2',7'-bis [2-carboxyethyl]-5[6]-carboxyfluorescein) the luminal perfusate pH is continuously measured with a microspectrofluorometric set-up, and the pH change following a sudden stop of perfusion is analysed. Because the tubules partially collapse after stop-flow the calculation of fluxes requires a correction for volume loss. This is achieved by referring all fluxes to the remaining luminal volume, which can be estimated from the decay of the 440 nm reference fluorescence. During perfusion of the lumen with pure HCO3- Ringer solution, and of the bath with the same solution but containing 5.5 mmol/l D-glucose as metabolic substrate, J(HCO3) averaged 4.4+/-0.2 pmol cm(-1) x s(-1) (n=40) and 13.4+/-0.8 pmol x cm(-1) x s(-1) (n=5) in proximal straight tubules (PST) and in proximal convoluted tubules respectively. These values agree very well with data obtained in other laboratories with the picapnotherm technique. The present method has the advantage of requiring fewer micromanipulations and a shorter measuring time, thus allowing regulatory changes in J(HCO3) to be analysed. Moreover it does not involve measurements of radioactivity, and it also allows J(H) to be measured in HCO3(-) free solutions which in PST averaged 0.9 pmol x cm(-1) x s(-1) (n=8) in the present experiments.

Luminal ATP stimulates fluid and HCO3- secretion in guinea-pig pancreatic duct.

1. The location of purinoceptors in the pancreatic duct and their role in regulating ductal secretion have been investigated by applying ATP and UTP to basolateral and luminal surfaces of pancreatic ducts isolated from the guinea-pig pancreas. 2. Changes in intracellular Ca2+ concentration were measured by microfluorometry in microperfused interlobular duct segments. Fluid and HCO3- secretion were estimated by monitoring luminal pH and luminal volume in sealed duct segments microinjected with BCECF-dextran. 3. Both ATP and UTP (1 microM) caused biphasic increases in intracellular Ca2+ concentration in pancreatic duct cells when applied to either the basolateral or luminal membrane. 4. Luminal application of both ATP and UTP evoked fluid and HCO3- secretion. The maximum response to 1 microM ATP or UTP was about 75 % of that evoked by secretin. By contrast, basolateral application of ATP or UTP inhibited spontaneous secretion by 52 % and 73 %, respectively, and secretin-evoked secretion by 41 % and 38 %, respectively. 5. The data suggest that luminal nucleotides may act in an autocrine or paracrine fashion to enhance ductal secretion while basolateral nucleotides, perhaps released from nerve terminals, may have an inhibitory effect. The fact that both apical and basolateral purinoceptors elevate intracellular Ca2+, but that they have opposite effects on secretion, suggests that additional signalling pathways are involved.

Invited editorial on "Neuromechanical interaction in human snoring and upper airway obstruction".

in this issue of the Journal, Huang and Ffowcs Williams ([3][1]) report the development of a mathematical model that couples flow mechanics of the upper airway with neurophysiological activity. The model depends on the mechanical principle that luminal collapse occurs when passive wall stiffness is

Blood volume in human bicuspid periodontal ligament determined by electron microscopy

The microvascular volume of periodontal ligament is reported to range from 1.63 to 3.5% in man, whereas that of animals varies from 7.5 to 11.5%. This transmission electron-microscopic investigation was undertaken to determine stereologically the volume in human periodontal ligament. The hypothesis tested was that the ligament blood volume in man is similar to that in animals. Left and right segments of mandible containing first and second premolars came from an adult burns’ victim who underwent jaw reconstruction. The segments were immersion-fixed in 2.5% glutaraldehyde, demineralized at 4°C in 0.1 M EDTA and processed for microscopy. Segments of distal periodontal ligament were sectioned at 150-μm intervals from the alveolar crest to the root apex and random tissue quadrats recorded for point counting and data analysis using a generalized linear-regression statistical model. Mean adjusted microvascular luminal volume was 9.52±2.28% (SEM) and the abluminal volume 12.91±2.76%; the wall volume was 3.39%. Significant differences existed between the luminal and abluminal volumes of the different vessel types ( p<0.05) and their distribution across the circumferential thirds of the ligament ( p<0.05). Total length density of the blood vessels was 149.84×10 3 cm/cm 3 and the surface density 330.19 cm 2/cm 3. Postcapillary-sized venules held 69.1% of the total blood volume and provided 49.3% of the luminal surface area. Venous capillaries were the most common vessel, comprising 48.5%, and they contributed 71.5% of the overall length density. This study confirmed the hypothesis for the blood volume in the periodontal ligament in man. Blood volumes do not reflect the configurations of microvascular beds.

Comparison of brachytherapy strategies based on dose-volume histograms derived from quantitative intravascular ultrasound

Purpose. We present in this paper the comparison, by simulation, of different treatment strategies based either on β- or γ-sources, both with and without a centering device. Ionizing radiation to prevent restenosis is an emerging modality in interventional cardiology. Numerous clinical studies are presently being performed or planned, but there is variability in dose prescription, and both γ- and β-emitters are used, leading to a wide range of possible dose distributions over the arterial vessel wall. This paper discusses the potential merits of dose-volume histograms (DVH) based on three-dimensional (3-D) reconstruction of electrocardiogram (ECG)-gated intravascular ultrasound (IVUS) to compare brachytherapy treatment strategies. Materials and Methods. DVH describe the cumulative distribution of dose over three specific volumes: (1) at the level of the luminal surface, a volume was defined with a thickness of 0.1 mm from the automatically detected contour of the highly echogenic blood-vessel interface; (2) at the level of the IVUS echogenic media-adventitia interface (external elastic lamina [EEL]), an adventitial volume was computed considering a 0.5-mm thickness from EEL; and (3) the volume encompassed between the luminal surface and the EEL (plaque + media). The IVUS data used were recorded in 23 of 31 patients during the Beta Energy Restenosis Trial (BERT) conducted in our institution. Results. On average, the minimal dose in 90% of the adventitial volume was 37 ± 16% of the prescribed dose; the minimal dose in 90% of the plaque + media volume was 58 ± 24% and of the luminal surface volume was 67 ± 31%. The minimal dose in the 10% most exposed luminal surface volume was 296 ± 42%. Simulations of the use of a γ-emitter and/or a radioactive source train centered in the lumen are reported, with a comparison of the homogeneity of the dose distribution. Conclusions. It is possible to derive DVH from IVUS, to evaluate the dose delivered to different parts of the coronary wall. This process should improve our understanding of the mechanisms of action of brachytherapy.

Reduced water permeability and altered ultrastructure in thin descending limb of Henle in aquaporin-1 null mice.

It has been controversial whether high water permeability in the thin descending limb of Henle (TDLH) is required for formation of a concentrated urine by the kidney. Freeze-fracture electron microscopy (FFEM) of rat TDLH has shown an exceptionally high density of intramembrane particles (IMPs), which were proposed to consist of tetramers of aquaporin-1 (AQP1) water channels. In this study, transepithelial osmotic water permeability (Pf) was measured in isolated perfused segments (0.5-1 mm) of TDLH in wild-type (+/+), AQP1 heterozygous (+/-), and AQP1 null (-/-) mice. Pf was measured at 37 degrees C using a 100 mM bath-to-lumen osmotic gradient of raffinose, and fluorescein isothiocyanate (FITC)-dextran as the luminal volume marker. Pf was (in cm/s): 0.26 +/- 0.02 ([+/+]; SE, n = 9 tubules), 0.21 +/- 0.01 ([+/-]; n = 12), and 0.031 +/- 0.007 ([-/-]; n = 6) (P < 0.02, [+/+] vs. [+/-]; P < 0.0001, [+/+] vs. [-/-]). FFEM of kidney medulla showed remarkably fewer IMPs in TDLH from (-/-) vs. (+/+) and (+/-) mice. IMP densities were (in microm-2, SD, 5-12 micrographs): 5,880 +/- 238 (+/+); 5,780 +/- 450 (+/-); and 877 +/- 420 (-/-). IMP size distribution analysis revealed mean IMP diameters of 8.4 nm ([+/+] and [+/-]) and 5.2 nm ([-/-]). These results demonstrate that AQP1 is the principal water channel in TDLH and support the view that osmotic equilibration along TDLH by water transport plays a key role in the renal countercurrent concentrating mechanism. The similar Pf and AQP1 expression in TDLH of (+/+) and (+/-) mice was an unexpected finding that probably accounts for the unimpaired urinary concentrating ability in (+/-) mice.

Small intestinal transit and digestibility of lactitol in Wistar rats.

The study was conducted to evaluate if the recovery of lactitol and its cleavage products varied when different doses of this disaccharide sugar alcohol (150 and 1,200 mg/kg body weight, respectively) were given by gastric gavage to unadapted male rats. Phenol red added to the test solution as marker dye served to determine the intestinal transit and distribution areas. Marker transit revealed that the test substance did not reach the cecum in all series. Gastric emptying was more retarded after the high dose. Administration of low doses did not alter intestinal transit and luminal volume as compared to control animals. But a much larger luminal volume was found in the third intestinal quarter after the high doses, although the marker transit through this segment was equal under all experimental conditions. The total gastrointestinal recovery of lactitol at 63.2 (+/- 3.9) and 75.5 (+/- 4.5)% was significantly different (p < 0.001) 1 hour after administration of 150 mg and 1200 mg/kg body weight, respectively. Only free sorbitol was detected in the gastrointestinal contents in both dosage groups. Based on these results and correcting the values for marker recovery (85% in both groups), it is reasonable to assume that the maximum amount of lactitol that can be hydrolyzed and absorbed by the small intestine is 11.2 and 25.2%, respectively, and not zero. In conclusion, the caloric availability of lactitol is dose-dependent and should be determined under normal conditions in which the laxative threshold is not exceeded.

Role of luminal volume changes in the increase in pulmonary blood flow at birth in sheep.

The mechanism by which pulmonary blood flow increases and pulmonary vascular resistance decreases after birth is not fully understood. The aim of this study was to simulate the decrease in lung volume caused by the onset of air-breathing at birth and determine whether it can duplicate the changes in pulmonary blood flow and vascular resistance that occur at this time. In chronically catheterized fetal sheep near term (145 days of gestation), fetal pulmonary arterial blood flow was measured, using coloured microspheres, before and after fetal lung liquid volumes were reduced from 52.2 +/- 2.7 to 21.2 +/- 1.6 ml kg-1. During the 30 min period following the reduction in lung liquid volume, the pulmonary-to-systemic arterial pressure difference decreased from 6.8 +/- 1.2 mmHg (pulmonary > systemic) to 1.6 +/- 0.5 mmHg. Reducing the volume of fetal lung liquid increased pulmonary blood flow from 59.1 +/- 10.5 to 204.2 +/- 40.4 ml min-1 (100 g tissue)-1 and reduced pulmonary vascular resistance from 0.53 +/- 0.20 to 0.14 +/- 0.04 mmHg min ml-1 (100 g tissue)-1. We conclude that a reduction in fetal lung liquid volume, which simulates the reduction in lung volume that occurs at birth, causes a 3- to 4-fold increase in pulmonary blood flow and a reduction in pulmonary vascular resistance of a similar magnitude. Thus, the reduction in lung volume associated with the lung changing from a liquid- to an air-filled organ, may partly account for the increase in pulmonary blood flow and decrease in pulmonary vascular resistance at birth.

Fluid secretion in interlobular ducts isolated from guinea-pig pancreas.

1. Pancreatic HCO3- and fluid secretion were studied by monitoring luminal pH (pHL) and luminal volume simultaneously in interlobular duct segments isolated from guinea-pig pancreas. The secretory rate and HCO3- flux were estimated from fluorescence images obtained following microinjection of BCECF-dextran (70 kDa, 20 microM) into the duct lumen. 2. Ducts filled initially with a Cl--rich solution swelled steadily (2.0 nl min-1 mm-2) when HCO3-/CO2 was introduced, and the luminal pH increased to 8.08. When Cl- was replaced by glucuronate, spontaneous fluid secretion was reduced by 75 %, and pHL did not rise above 7.3. 3. Cl--dependent spontaneous secretion was largely blocked by luminal H2DIDS (500 microM). We conclude that, in unstimulated ducts, HCO3- transport across the luminal membrane is probably mediated by Cl--HCO3- exchange. 4. Secretin (10 nM) and forskolin (1 microM) both stimulated HCO3- and fluid secretion. The final value of pHL (8.4) and the increase in secretory rate (1.5 nl min-1 mm-2) after secretin stimulation were unaffected by substitution of Cl-. 5. The Cl--independent component of secretin-evoked secretion was not affected by luminal H2DIDS. This suggests that a Cl--independent mechanism provides the main pathway for luminal HCO3- transport in secretin-stimulated ducts. 6. Ducts filled initially with a HCO3--rich fluid (125 mM HCO3-, 23 mM Cl-) secreted a Cl--rich fluid while unstimulated. This became HCO3--rich when secretin was applied. 7. Addition of H2DIDS and MIA (10 microM) to the bath reduced the secretory rate by 56 and 18 %, respectively. Applied together they completely blocked fluid secretion. We conclude that basolateral HCO3- transport is mediated mainly by Na+-HCO3- cotransport rather than by Na+-H+ exchange.

Novel adaptation of a method to assess responsiveness of bronchial segments in vitro.

In vivo agonist delivery to the lungs is characterized by absorption through the mucosal layer followed by access to the smooth muscle. When agonists are applied to perfused bronchial segments, a difference in potency to agonists applied to the serosal (outside) or mucosal (inside) surface can be demonstrated. In order to elucidate this effect in canine bronchial segments, we adapted a method to assess responsiveness of agonists applied to the inside or outside surface of canine bronchial segments. A 2 cm "fluid-tight" length of bronchus was cannulated and mounted in a perfusion chamber. Auxotonic contraction of the bronchus displaced fluid inside the segment up a column and the change in height of fluid within the column (afterload) was measured as a change in hydrostatic pressure (volumetric). We assessed the optimal conditions for measuring bronchial responsiveness to acetylcholine. Neither stretching segments lengthways from 100 to 140% of resting length, nor altering the transmural pressure from 3 to 21 cmH2O had a significant effect on the potency of acetylcholine applied to the outside surface. Both acetylcholine (n=7) and methacholine (n=4) were approximately 10-fold more potent when applied to the outside surface than the inside surface of bronchial segments (p<0.0001). Furthermore, mechanical removal of the epithelium (n=6) led to a 67-fold increase in potency of acetylcholine applied to the inside surface compared with segments with epithelium. The advantages that this system has over previously reported methods include: 1) agonists can be injected at a low flow rate so as to minimize epithelial stress; 2) changes in luminal volume are measured under conditions of no flow; 3) after-load can be varied such that contraction is either practically isotonic or auxotonic; and 4) a "barrier effect" of the epithelium of canine bronchial segments can be demonstrated. This new adapted method will provide us with the means to assess the relationship between in vitro and in vivo responsiveness in human bronchi.

Application of magnetic resonance imaging for evaluation of the efficacy of SB 217242 in neointimal formation.

Although several factors have been implicated in the pathophysiology of vascular neointimal formation and restenosis after balloon angioplasty, current therapies have failed to alleviate these conditions. Because endothelin-1 (ET-1) has been implicated in the pathogenesis of the neointimal growth, this study examined the in vivo efficacy of SB 217242, a potent nonpeptide mixed ETA/ETB receptor antagonist with high oral bioavailability, in the rat carotid balloon angioplasty model. A novel magnetic resonance imaging (MRI) approach was used for evaluation. MRI is a high-resolution, noninvasive spatial imaging modality that can serially monitor arterial luminal caliber in vivo, along with histologic evaluation. In vivo luminal volumes for the left carotid artery (LCA) were measured by MRI at baseline (before surgery) and again at 14 days after angioplasty. SB 217242 (30 mg/kg/day p.o.) was administered daily for 14 days after angioplasty. On day 14, SB 217242 provided 20% protection (p < 0.05) on neointimal-mediated decrease in luminal volume as measured by MRI. The non-ballooned right carotid arteries of both groups had significantly increased luminal volume on day 14 with respect to baseline values, indicating compensation for the decreased luminal size of the LCA. Histologic analysis of the mean intimal-to-medial ratio demonstrated that SB 217242 provided 42% (p < 0.05) protection. These results demonstrate that ET receptor antagonism can inhibit neointimal formation after balloon angioplasty and that MRI technology can provide valuable insight for noninvasive assessment of vascular lesion development.

Langur prostate and its hormonal modulation.

The normal histoarchitecture of langur prostate of different growth phases, viz., juvenile, sub-adult, and adult, and the hormonal modulation of adult prostate were studied in order to explore its suitability of a surrogate for human prostate. The histological observations revealed that the langur prostate is histoarchitecturally homogeneous. The volumetric composition of stroma (%) was found to be decreased significantly from juvenile to adult and that of epithelium and lumen was found to be increased significantly. The absolute volume (c.c.) of stroma, epithelium, and lumen increased significantly from juvenile to adult. A marked depletion in the various prostatic fluid biochemical parameters was observed in castration groups, which were recovered to control level following testosterone enanthate administration. The castration induced significant increase in volumetric composition of stroma; conversely that of the epithelium and lumen decreased significantly. The absolute volume of stroma did not show any appreciable variation, while that of epithelium and lumen decreased significantly. The inter acinar stroma decreased from juvenile to adult, while the lumen diameter increased significantly from juvenile to adult. Castration increased the inter acinar and lumen diameter; conversely the epithelial height decreased. The testosterone supplementation restored the prostate. However, the volumetric composition of stroma remained high, while the luminal volume remained low. Various prostatic parameters in normal and under altered hormonal conditions suggest that the langur prostate is similar to the human and therefore could be used as surrogate for the human prostate.

Endothelin-A receptors mediate vasoconstriction of capillaries in the spiral ligament

The purpose of this study was to determine whether endothelin-1 (ET-1), endothelin-2 (ET-2) or endothelin-3 (ET-3) alter the vascular diameter of capillaries in the spiral ligament. Changes in vascular tone were measured in capillaries from the isolated spiral ligament in vitro. Capillaries were occluded on one end and opened on the other end. Red blood cells trapped in the capillaries served as markers for a luminal volume defined by the red cell itself, the capillary wall and the occluder. Movement of the red cell toward the open end was taken as evidence for vasoconstriction and movement of the red cell toward the occluder was taken as evidence for vasodilation. The inner diameter of the capillaries was 7.0 μm and decreased maximally by a factor of 0.8 in response to ET-1 and ET-2 (both 10 −8 M). Vasoconstriction induced by ET-1 and ET-2 was concentration-dependent in the range between 10 −12 and 10 −8 M whereas ET-3 (10 −8 M) had no effect. The EC 50S for ET-1 and ET-2 were 1.2 × 10 −10 M and 1.4 × 10 −9 M, respectively. Thus, the potency order was ET-1 > ET-2 ⪢ ET-3. Vasoconstriction induced by ET-1 and ET-2 was completely inhibited by the competitive antagonist 10 −6 M BQ-123 (cyclic d-Asp- l-Pro- d-Val- l-Leu- d-Trp). Vasoconstriction induced by ET-1 or ET-2 continued for more than 1 min after removal of agonist from the perfusate. Rapid vasodilation of capillaries preconstricted by ET-1 was observed in response to 10 −3 M sodium nitroprusside. Sodium nitroprusside, however, had no significant effect on the vascular diameter of resting capillaries. These results demonstrate that capillaries in the spiral ligament can constrict and the endothelin-mediated vasoconstriction occurs via ET A receptors.

A quantitative description of dynamic left ventricular geometry in anaesthetized rats using magnetic resonance imaging.

We report a functional application of magnetic resonance imaging (MRI) for the quantitative description of left ventricular geometry through systole and diastole in normal anaesthetized Wistar rats that might be applicable for the analysis of chronic changes resulting from pathological conditions. Images of cardiac anatomy were acquired through planes both parallel and perpendicular to the principal cardiac axis at times that were synchronized to the R wave of the electrocardiogram. The images of the transverse sections were assembled into three-dimensional representations of left ventricular geometry at consecutive time points through the cardiac cycle. This confirmed the geometrical coherence of the data sets, that each slice showed circular symmetry, and that the images were correctly aligned with the appropriate anatomical axes. Different models for the three-dimensional geometry of the left ventricle were then tested against the epi- and endocardial surfaces reconstructed from images of the transverse sections of the left ventricle in both systole and diastole using least-squares minimizations in three dimensions. In agreement with previous reports in the human heart, an elliptical figure of revolution offered an optimal fit to the epicardial and endocardial geometry for the rat heart in diastole. This was in preference to models that used spherical, quartic or parabolic geometries. However, in contrast to contraction in the human heart, all these geometrical representations broke down during systolic ejection in the rat heart. We therefore introduced a more general hybrid model which described left ventricular geometry in terms of the variation of the radii r(z), independently determined for each slice, with its position z along the principal cardiac axis. The resulting function r(z) could then be described by a simple ellipsoid of revolution not only during diastole, but also throughout ventricular ejection. The findings also ruled out alternative geometrical representations. It was then possible additionally to reconstruct the luminal and total left ventricular volumes, wall thicknesses and ejection fractions through the cardiac cycle and to confirm that the predicted total ventricular wall volume was conserved throughout the cardiac cycle. Our hybrid model of cardiac geometry may thus be useful for non-invasive serial studies of chronic pathological changes that use the rat as a model experimental system.

Bronchial compliance and wall structure during development of the immature human and pig lung.

Maturational changes in the specific compliance could potentially contribute to the development or clinical presentation of respiratory diseases in infants and children. Changes in the specific compliance during development and its structural basis have been well characterized, but changes in bronchial compliance and the mechanisms involved have received little attention. Semistatic pressure-volume curves were generated for isolated bronchial segments from late-term foetal, immature and adult pigs. A small number of bronchi from human infants were also studied. The amount of cartilage in the bronchial wall of pigs of different ages was measured histologically, and morphometric changes in the wall of inflated bronchi were investigated. The specific compliance of bronchi approximately halved from 1 to 4 weeks of age. No change in specific compliance was observed either between 4 week old and adult pigs, or between late-term foetal and 1 week old pigs. Changes in the total wall and cartilage areas did not correlate with changes in specific compliance. Inflation to 20 cmH2O transmural pressure reduced the total wall area of bronchi from 1 week old pigs. Significant changes in bronchial distensibility occur during the early postnatal period. These changes in specific compliance are not caused by an increase in the amount of cartilage. The increase in luminal volume during inflation of bronchial segments occurs, partially, by compression of the airway wall against the cartilage layer.

Role for insulin-like growth factor I in the regulation of electrolyte composition of uterine luminal fluid.

A potential role for insulin-like growth factor I (IGF-I) in the regulation of the uterine electrolyte environment was studied in conjunction with hyperoestrogenaemia caused by superovulation. Uterine luminal fluid from immature rats treated with 4 (control), 10, 20 and 40 i.u. (superovulation) pregnant mares' serum gonadotrophin (PMSG, day -2) and the electrolyte composition was determined on day 3 of pregnancy. Superovulation increased total cation content in uterine flushes by more than twofold, suggesting a comparable increase in the uterine luminal fluid volume. Percentages of K+ and HCO-3 content to total cations or anions increased by 27% and 16%, respectively, and those of Na+ and Cl- decreased by 26% and 15%, respectively, after superovulation. Daily injections with 1.0 micrograms or more oestradiol, from day 0 to day 2, in the 4 i.u. PMSG-primed immature rats caused similar changes in total cation content and electrolyte composition of uterine luminal fluid. Anti-IGF-I antibody infusion in the superovulated or oestradiol-treated immature rats restored the alterations in cation composition but had no effect on anion composition and total cation content. IGF-I was infused into adult rats to achieve increased IGF-I action observed after superovulation. IGF-I infusion altered electrolyte composition, as is observed after superovulation or oestradiol treatment, but had no effect on total cation content. In conclusion, hyperoestrogenaemia caused by superovulation may alter the uterine electrolyte environment for preimplantation embryonic development. IGF-I appears to play a central role in mediating this action of oestrogen.