Bisphenol-A analogs induce lower urinary tract dysfunction in male mice.

Bisphenol-A (BPA), an estrogenic endocrine disrupting chemical, significantly impacts numerous diseases and abnormalities in mammals. Estrogens are known to play an important role in the biology of the prostate; however, little is known about the role of bisphenols in the etiology of prostate pathologies, including benign prostate hyperplasia (BPH) and associated lower urinary tract dysfunction (LUTD). Bisphenol-F (BPF) and bisphenol-S (BPS) are analogs often used as substitutes for BPA; they are both reported to have in vitro and in vivo estrogenic effects similar to or more potent than BPA. The objective of this study was to assess the role of these bisphenols in the development of LUTD in adult male mice. In adult mice exposed to BPA, BPS or BPF, we examined urinary tract histopathology and physiological events associated with urinary dysfunction. Mice treated with bisphenols displayed increased bladder (p < 0.005) and prostate (p < 0.0001) mass, and there was an increased number of prostatic ducts in the prostatic urethra (p < 0.05) and decreased size of the urethra lumen (p < 0.05) compared to negative controls. After two months of bisphenol exposure, mice displayed notable differences in cystometric tracings compared to controls, consistent with LUTD. Treatment of male mice with all bisphenols also induced voiding dysfunction manifested by detrusor instability and histologic changes in the prostatic urethra of male rodents, consistent with LUTD. Our results implicate BPA and its replacements in the development and progression LUTD in mice and provide insights into the development and progression of BPH/LUTS in men.

Evidence of the growth plate and the growth of long bones in juvenile dinosaurs.

Histological and ultrastructural evaluation of the ends of long bones of juvenile dinosaurs from the Upper Cretaceous Two Medicine Formation of Montana revealed the preservation of growth plates. Growth plates are discs of cartilage present near the ends of growing long bones that generate bone elongation. Comparison of the fossils with modern taxa demonstrated homology of the growth plate in birds and dinosaurs. The presence of an avian-type growth plate in dinosaurs adds a shared derived anatomical character corroborating inclusion of birds within the Dinosauria. Additionally, possession of a growth plate, which in birds is capable of producing rapid determinate long bone growth, implies that an avian developmental pattern may have been present in these dinosaurs.

Sustained hypoxia-induced proliferation of carotid body type I cells in rats.

Sustained hypoxia (SH) has been shown to cause profound morphological and cellular changes in carotid body (CB). However, results regarding whether SH causes CB type I cell proliferation are conflicting. By using bromodeoxyuridine, a uridine analog that is stably incorporated into cells undergoing DNA synthesis, we have found that SH causes the type I cell proliferation in the CB; the proliferation occurs mainly during the first 1-3 days of hypoxic exposure. Moreover, the new cells survive for at least 1 mo after the return to normoxia. Also, SH does not cause any cell death in CB as examined by the terminal deoxynucleotidyl transferase-mediated dUTP-X nick-end labeling assay. Taken together, our results suggest that SH stimulates CB type I cell proliferation, which may produce long-lasting changes in CB morphology and function.

Pyloric obstruction secondary to epicardial pacemaker implantation: a case report.

A 10-year old Lhasa Apso dog was presented for an acute history of exercise intolerance and hind limb weakness. High grade second degree atrioventricular block with an atrial rate of 200 beats per minute, ventricular rate of 40 beats per minute and an intermittent ventricular escape rhythm, was diagnosed on electrocardiograph. A transdiaphragmatic, unipolar, epicardial pacemaker was implanted without immediate surgical complications. Severe vomiting was noted 12 h post-operatively. Abdominal ultrasound and a barium study supported a diagnosis of pyloric outflow obstruction and exploratory abdominal surgery was performed. The pyloric outflow tract appeared normal and no other causes of an outflow obstruction were identified. The epicardial generator was repositioned from the right to the left abdominal wall. Pyloric cell pacing was presumed to be the cause for the pyloric obstruction and severe vomiting, and this was thought to be due to close proximity of the pacemaker generator to the pylorus situated in the right abdominal wall. Repositioning of the pulse generator to the left abdominal wall resulted in resolution of vomiting.

Modulation of nerve growth factor in peripheral organs by estrogen and progesterone.

Nerve growth factor (NGF) synthesized in peripheral organs plays a critical role in the development and maintenance of the nervous system and also participates in processing nociceptive stimuli. Previous studies suggest that reproductive hormones may regulate the expression of NGF. Ovariectomies were performed on female mice, and mice were killed 24 h after hormone replacement to evaluate the effects of estrogen and progesterone on NGF in peripheral organs, specifically the uterus, bladder, heart, and salivary gland. Sham-operated intact mice and untreated ovariectomized mice served as controls. Immunohistochemistry demonstrated the presence of NGF, estrogen receptor-alpha, estrogen receptor-beta, and progesterone receptors in these organs. Ovariectomy caused a significant decrease in NGF protein content in the uterus, and short term treatment of ovariectomized mice with estrogen and/or progesterone increased uterine NGF mRNA and restored NGF protein to concentrations similar to intact control mice. Ovariectomy did not affect NGF protein concentrations in the salivary gland, but treatment of ovariectomized mice with estrogen alone or in conjunction with progesterone stimulated concentrations of NGF protein that exceeded those observed in intact control or ovariectomized, untreated mice. NGF mRNA was increased in salivary glands from ovariectomized mice treated with progesterone alone or in combination with estrogen relative to other groups. NGF protein content of the hearts of ovariectomized mice treated with estrogen alone or in conjunction with progesterone was increased relative to intact controls and ovariectomized, untreated mice, but neither ovariectomy or hormone replacement affected NGF mRNA content in the heart. NGF protein content of the bladder was unaffected by ovariectomy or hormone treatment, and bladder NGF mRNA was unaffected by ovariectomy or hormone treatment. Collectively, these results indicate that reproductive hormones have the capacity to regulate NGF message and protein in a manner that varies among organs. Fluctuations in the expression of NGF, in conjunction with other factors, may help to explain gender differences in pain sensation and inflammatory response.

Distribution of neuropeptides, histamine content, and inflammatory cells in the ureter.

OBJECTIVES: To determine the anatomic distribution of select neuropeptides (neurokinin A [NKA], substance P [SP], and bradykinin [BK]), of inflammatory cells (leukocytes and mast cells), and the histamine content in the normal swine ureter and compare the findings with regions of increased ureteral contractility. METHODS: Ureters from 10 pigs were obtained and cut into eight segments, proximally to distally. A portion of each ureteral segment was suspended in Krebs buffer (37 degrees C) and attached to force displacement transducers, and spontaneous contractility was measured for 30 minutes. A second portion was assayed for histamine, NKA, SP, and BK using enzyme-linked immunosorbent assay. A third portion was fixed in 10% buffered formalin, stained with hematoxylin-eosin, and evaluated histologically. RESULTS: Ureteral contractility was found to be highest in the most proximal and most distal regions of the ureter. Similarly, SP content was three times greater in the proximal ureter and two times greater in the distal ureter than in the midureter (P <0.05, n = 10). The total NKA and BK content were also higher in the proximal and distal ureter than in the midureter. Conversely, the histamine content was consistent throughout the ureter. Moreover, no significant difference in the distribution of inflammatory cells was identified throughout the ureter. CONCLUSIONS: The anatomic distribution of NKA, SP, and BK in the ureter corresponded to regions of increased spontaneous ureteral contractility, more specifically the proximal and distal ureter. Neuropeptides may play a significant role in ureteral contractility and may be a target for pharmacologic mediation during obstruction and stone passage.

Use of gold-labeled ovalbumin to correlate antigen deposition and localization with tissue response.

This study was performed to evaluate a technique for correlating the location of antigen within sensitized tissues with physiological response. Guinea pigs actively sensitized by intraperitoneal injection of ovalbumin (OVA) were euthanized, and urinary bladders were removed. Gold beads (18 nM diameter) were conjugated to OVA (OVA-Au) and bovine serum albumin (BSA-Au). Bladder tissue was suspended in tissue baths, exposed to OVA, OVA-Au, BSA, and BSA-AU, and tissue contraction and histamine release were determined. Bladder tissues were examined by electron microscopy to determine distribution of gold-labeled antigen at 1 and 5 min after exposure. Exposure of bladder tissue from sensitized guinea pigs to OVA stimulated concomitant contraction and histamine release which reached maximal levels within 3 min; bladder tissue from control, nonsensitized guinea pigs did not respond to OVA. BSA failed to stimulate response from OVA-sensitized or control bladder tissue. Labeled antigen was adhered to mucosa of sensitized bladder tissue 1 min after exposure to OVA-Au. OVA-Au was present within the mucosa and submucosa of sensitized tissues within 5 min. OVA-Au did not adhere to, or become internalized by, control tissues, and BSA-Au did not adhere to, or become internalized by, any tissues. Labeling of antigen with gold allowed the location of antigen within tissues to be determined and did not affect the response of sensitized tissues to antigen exposure.

Removal of venous endothelium with air.

Much research on the activity and half-life of endothelium-derived substances has entailed the removal of endothelium from arteries by mechanical or enzymatic processes. It has been observed that the technique used for the removal of arterial endothelium may profoundly affect smooth muscle function and release of prostanoids by the vessel wall. The function and patterns of regeneration of arterial endothelium have been extensively described, but there is a relative paucity of information about the venous endothelium, due in part to the difficulty of its removal. We developed a technique for removal of the endothelium of rabbit femoral veins by passing a stream of air through the lumen of the vessel to dry and remove the endothelium. The effectiveness of endothelium removal was verified by the lack of in vitro reactivity to endothelium-dependent relaxing substances, examination of frozen sections of vessels, labeled with fluorescent-tagged acetylated low-density lipoprotein, with fluorescent light microscopy and scanning electron microscopy of vessel segments. Air drying effectively removed the endothelium and abolished mechanical responses to endothelium-dependent vasodilators but did not affect the function of the smooth muscle. We propose the use of air to remove endothelium from veins to be used to study endothelium-derived factors since this method achieves complete removal of endothelium without causing detectable damage (morphological or functional) to the remainder of the vessel wall.

High-frequency jet ventilation during pneumothorax in dogs.

Pneumothorax (45 ml of N/kg of body weight insufflated into the pleural space) in anesthetized dogs ventilated with air caused a significant (P less than 0.05) increase in pleural pressure, central venous pressure, capillary wedge pressure, and venous admixture. Cardiac index (CI) and arterial O2 tensions were decreased. Ventilation with 100% O2 increased arterial O2 tensions, but did not affect calculated intrapulmonary shunting of blood or CI. Application of 10 cm of H2O-positive end-expiratory pressure in the presence of pneumothorax during positive-pressure ventilation and high-frequency jet ventilation reduced intrapulmonary shunting of blood, which remained higher than control values, and caused a further decrease in CI. Cardiopulmonary function during pneumothorax in anesthetized dogs was more profoundly affected by the application of positive end-expiratory pressure than by the form of mechanical ventilation.

Effect of humidification on the airways of cats during high-frequency ventilation.

The effect of humidity on the histologic lesions induced by high-frequency jet ventilation was investigated in 12 healthy cats. After 16 hours of ventilation, the appearance of the tracheal epithelium ranged from normal to necrotic. The damage was considerably more severe in the trachea of cats of the group ventilated without added humidity. Increasing the relative humidity to 63% at 24 C had a protective effect, but further increasing the relative humidity to 92% at 35 C did not appear to provide significantly more protection. The bronchi and distal airways had minimal, if any, damage in all groups.

Clearance of indocyanine green in dogs with partial hepatectomy, hepatic duct ligation, and passive hepatic congestion.

Clearance of 5 submaximal doses of indocyanine green (ICG) was measured in 5 dogs to determine the maximal removal rate (0.188 mg/kg of body weight/min) and Michaelis constant (Km, 1.25 mg/kg). From these results, 5 mg of ICG/kg of body weight was chosen on the basis of the recommendation that the dose should be at least 4 X Km to achieve sensitivity as a measure of hepatic function and independence from hepatic blood flow. Clearances of low (0.5 mg/kg) and high (5 mg/kg) doses of ICG were measured in 35 healthy dogs to determine reference values. Fractional disappearance was 15.1 +/- 10%/min for the low dose and 3.9 +/- 1%/min for the high dose; plasma half-life was 6.3 +/- 3.6 minutes and 19 +/- 4.8 minutes, respectively. The sensitivity of 2 doses of ICG was evaluated in dogs with 20% and 40% hepatectomy, nonhyperbilirubinemic obstructive cholestasis, or hepatic congestion; sham-operated dogs served as controls. Fractional disappearance and plasma half-life of ICG in the 40% hepatectomy and hepatic congestion groups were significantly different (P less than 0.05) from those in controls using both ICG doses, indicating that both doses were affected by hepatic perfusion, as well as hepatic mass. The fractional disappearance of the dye in the cholestasis group also differed significantly (P less than 0.05) from that of the controls at the high dose. Plasma clearance of both doses by dogs with 20% hepatectomy was not significantly different from that of controls.

Diagnostic peritoneal lavage before and after abdominal surgery in dogs.

Complete blood cell counts and peritoneal lavage (PL) were done 2 days before and 2 days after abdominal surgery. Abdominal surgery consisted of intestinal resection/anastomosis and cystotomy in 18 dogs in group 1 and gastrotomy, pyloromyotomy, and repair of diaphragmatic laceration in 20 dogs in group 2. Insertion of the dialysis catheter for PL preoperatively in a right paramedian location resulted in more PL samples contaminated with blood than when the catheter was inserted on the abdominal midline. The number of nucleated cells found in PL fluid when the catheter was inserted in a right paramedian location was not significantly different (P less than 0.05) from that observed in PL fluid collected after insertion of the catheter through the abdominal midline. The predominant cell type in preoperative PL fluid was the segmented neutrophil. In groups 1 and 2, WBC counts and nucleated cell counts in PL fluid were significantly increased (P less than 0.05) postoperatively. Segmented neutrophils and macrophages were most frequently present in postoperative PL fluid. Degenerative neutrophils in postoperative PL fluid were associated with the appearance of immature neutrophils in the blood and increased rectal temperature. Dogs with these findings appeared to have more peritoneal inflammation at necropsy than did others in their groups. Concentrations of alkaline phosphatase, alanine aminotransferase, amylase, and creatinine in preoperative PL fluid were extremely low. Except for creatinine in group 2, all of these were significantly increased (P less than 0.05) postoperatively. The complication rate associated with the performance of PL on dogs postoperatively was not greater than that which was observed preoperatively.

Evaluation of intestinal villus height in rats after ischemia and reperfusion by administration of superoxide dismutase, polyethylene glycol-conjugated superoxide dismutase, and two 21-aminosteroids.

Intestinal ischemia was induced and maintained for 60 minutes in male Sprague-Dawley rats weighing 175 to 225 g. Prior to reperfusion, the following drugs were administered via the caudal vena cava: 0.9% NaCl (0.5 ml), superoxide dismutase (SOD; 1,000 IU/kg of body weight), polyethylene glycol-conjugated SOD (PEG-SOD; 1,000 IU/kg), or the 21-aminosteroids, U74006F (3 mg/kg) or U78715G (3 mg/kg). A sham-operated control group was included. Animals from each group were euthanatized at 5 periods of reperfusion: 5 minutes, 30 minutes, 18 hours, 3 days, and 7 days after reperfusion. Fixed tissues were embedded in paraffin, sectioned at 5 microns, and stained with H&E. Villi profiled in cross section were measured from the crypt villus junction to the tip of the villus. The mean villus height for each rat was calculated and compared by two-way ANOVA to determine the effects of time and treatment. Villus height was maintained after 30 minutes of reperfusion in rats of the sham- and U74006F-treated groups; U78715G and SOD treatment attenuated the loss in villus height, and villus height was not maintained in the PEG-SOD- and 0.9% NaCl-treated rats. In all rats, villus height was comparable to, or was greater than villus height in sham-operated controls by 18 hours after reperfusion in all animals and remained constant through 7 days. Administration of the 21-aminosteroids maintained villus height after ischemia and reperfusion. Treatment with PEG-SOD did not maintain villus height to the degree observed in rats treated with SOD.

Evaluation of Key's hypothesis in the feline tibia: an experimental model for augmented bone healing studies.

Key's hypothesis states that a segmental long bone defect 1.5 times the diaphyseal diameter exceeds the regenerative capacity of bone in skeletally mature dogs and results in nonunion. This hypothesis was evaluated in 5 adult cats with rigidly fixated segmental tibial ostectomies ranging from 1.25 to 1.52 times the diaphyseal diameter. Clinical, radiographic, and histologic data were obtained over a 12-week period. Healing was classified as mature bony union, clinical union, delayed union, or nonunion. Absence of a consolidating callus and instability after removal of fixation devices was found for all cats at 12 weeks. Scant formation of new bone within the gap was histologically evident for only 1 cat. In the remaining 4 cats, fibrous tissue and striated muscle predominated within the gap, and independent healing of the proximal and distal cut ends of the bone were observed. The occurrence of 4 nonunions and 1 equivocally delayed union indicated that Key's hypothesis overestimates the regenerative capacity of bone in the cat. Failure of this experimental model to produce clinical union within 12 weeks demonstrated that this model is a valid method of investigating augmented bone healing techniques that promote union within this period in the cat.

Indocyanine green clearance and ammonia tolerance in partially hepatectomized and hepatic devascularized, anesthetized dogs.

Indocyanine green clearance and ammonia tolerance were measured in anesthetized dogs with 60% hepatectomy, 40% hepatectomy, portacaval shunt, and hepatic artery ligation. With a dose of 0.5 mg of indocyanine green/kg of body weight, plasma clearance of the dye was significantly (P less than 0.001) delayed only in dogs with 60% hepatectomy. Ammonia tolerance was abnormal in dogs in this group, because after they were given a gastric challenge load of an ammonium salt, they had a 5-fold increase in plasma ammonia concentration, compared with a 2.5-fold increase in the control group. Before challenge loading, base-line plasma ammonia concentration was significantly (P less than 0.05) increased within 5 minutes after surgical preparation of the portacaval shunt. After challenge loading the stomach with an ammonium salt, dogs with portacaval shunt had increased plasma ammonia concentration, but the amount was not significantly different from postchallenge-loading values in control dogs. Dogs with 40% hepatectomy and with hepatic artery ligation could not be differentiated from control dogs by indocyanine green clearance or by ammonia tolerance testing. Abnormal tolerance to a challenge gastric load of an ammonium salt or delayed clearance of indocyanine green may indicate marked loss of functional hepatic mass, but normal tolerance or normal dye clearance may not exclude liver disease or dysfunction. Seemingly, base-line plasma ammonia concentration was a sensitive indicator of abnormal portal circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Pasteurella haemolytica leukotoxin and lipopolysaccharide on histamine, prostanoid, and leukotriene release by bovine lung parenchyma in vitro.

OBJECTIVE: To identify the effect of Pasteurella haemolytica lipopolysaccharide (LPS) and leukotoxin (LKT) on spontaneous and calcium ionophore-induced histamine and inflammatory mediator release from isolated bovine lung parenchyma. SAMPLE POPULATION: Lungs from 8 healthy cattle. PROCEDURE: Isolated bovine lung parenchyma was incubated in vitro for 2 hours with LKT or LPS, and spontaneous and induced release of inflammatory mediators was determined. RESULTS: LKT and LPS increased spontaneous release of histamine and leukotriene B4. In addition, incubation with LPS increased spontaneous release of prostaglandin E2. Moreover, a differential effect of the 2 toxins on calcium ionophore-induced inflammatory mediator release was observed. LKT specifically primed isolated lung parenchyma to release leukotriene B4 and thromboxane B2 in response to calcium ionophore, whereas LPS did not alter the profile of prostanoids released by bovine lung tissue exposed to calcium ionophore. CONCLUSIONS: Pasteurella haemolytica toxins have a direct effect on bovine lung parenchyma, causing release of inflammatory mediators, which contribute to response to infection. Furthermore, bacterial toxins (LKT in this study) may sensitize tissues to the effects of other irritant stimuli, amplifying the inflammatory response.

Canine hemangiopericytoma: 23 cases (1967-1984).

The medical records of 23 histopathologically confirmed cases of canine hemangiopericytoma were reviewed. Ninety-one percent (21/23) of the dogs were 7 years old or older, and 70% (16/23) were female. Seventy-four percent (20/27) of the tumors developed on the extremities. Recurrence rates were 31% (5/16) with surgical excision only, and 60% (3/5) with surgical excision combined with radiotherapy. Tumor recurrence did not appear to be related to mitotic index. Metastasis was suspected in one of the dogs, but was not confirmed.

High-frequency jet ventilation during bronchoscopy in a dog.

A dog with severe pulmonary disease caused by Filaroides osleri (Oslerus osleri) infection was anesthetized with thiopental sodium IV for diagnostic bronchoscopy. The dog was ventilated continuously during bronchoscopy with a high-frequency jet ventilator (using a rate of 100 breaths/min, drive pressure of 20 psi, and inspiratory fraction of 0.30). High-frequency jet ventilation provided satisfactory ventilatory support during bronchoscopy despite the dog's pulmonary disease.

Effects of hydromorphone or oxymorphone, with or without acepromazine, on preanesthetic sedation, physiologic values, and histamine release in dogs.

OBJECTIVE: To compare hydromorphone with oxymorphone, with or without acepromazine, for preanesthetic sedation in dogs and assess changes in plasma concentration of histamine after drug administration. DESIGN: Randomized clinical study. ANIMALS: 10 healthy mixed-breed dogs. PROCEDURE: Dogs were treated IM with hydromorphone (group H), oxymorphone (group O), hydromorphone with acepromazine (group H/A), or oxymorphone with acepromazine (group O/A). Sedation score, heart rate, respiratory rate, systolic blood pressure, and oxygen saturation were recorded at baseline immediately after drug administration (T0) and every 5 minutes for 25 minutes (T25). Plasma histamine concentration was measured at baseline and T25. RESULTS: Sedation was similar between groups H and 0 at all times. Sedation was significantly greater for groups H/A and O/A from T10 to T25, compared with other groups. Systolic blood pressure was significantly reduced at T25 in group H/A, compared with group H, and in group O/A, compared with group O. Prevalence of panting at T25 was 50% for groups H and O, compared with 20% for group H/A and 30% for group O/A. By T25, heart rate was significantly lower in all groups. Oxygen saturation was unaffected by treatment. Mean +/- SD plasma histamine concentration was 1.72 +/- 2.69 ng/ml at baseline and 1.13 +/- 1.18 ng/ml at T25. There was no significant change in plasma histamine concentration in any group. CONCLUSIONS AND CLINICAL RELEVANCE: Hydromorphone is comparable to oxymorphone for preanesthetic sedation in dogs. Sedation is enhanced by acepromazine. Neither hydromorphone nor oxymorphone caused an increase in plasma histamine concentration.

Cervical spinal luxation in two dogs with entrapment of the cranial articular process of C6 over the caudal articular process of C5.

In 2 Poodles, the cranial articular process of C6 was luxated and interlocked dorsal to the caudal articular process of C5. Surgical management in each case included reduction and stabilization of the articular processes, along with limited dorsal laminectomy. One of the dogs was completely normal 4 weeks after surgery, but the other had residual neurologic deficits 11 months after injury.