The persistence of emamectin benzoate in marine sediments with different organic matter regimes, temperature conditions, and antibiotic presence.

The objectives of this 318-day study are to determine half-lives of the anti-sea lice medication emamectin benzoate (EMB) under conditions present in sediments at aquaculture sites and document the degradation of EMB into its main metabolite desmethyl emamectin benzoate (DES). Tested conditions include different matrix types (sand, mud), two temperatures (4, 10 degrees), organic matter presence (fish feed waste and feces), and the presence of oxytetracycline. We document a transformation ratio of EMB to DES of 0.16 to 4.4 % and show that the co-presence of oxytetracycline increases EMB calculated half-lives to values >6000 days for mud matrices. EMB incubated in high organic enrichment regimes was not observed to degrade at 4 degrees. Multivariate analyses show interactions between sediment conditions (matrix, temperature, organic matter [OM], oxytetracycline) influence EMB persistence and DES:EMB ratios. Ranges of EMB half-lives and information on metabolites can be used to anticipate potential effects on marine communities.

Metabolization of emamectin benzoate into desmethyl emamectin benzoate in spiked marine sediments.

Emamectin benzoate (EMB) (4″deoxy- 4″-epi-methylaminoavermectin) is a pesticide developed to control pests on various crops, and in forestry. It is also used in salmon aquaculture to control sea lice infestations as an in-feed therapeutant. Little is known about EMB metabolites and potential associated toxicities in marine sediments. In this study, we used natural marine sediments (sand and mud) fortified at an EMB concentration of 60 ppb (wet weight). Results show an almost immediate transformation of EMB to Desmethyl EMB (DES) with no increased rates of metabolization when stored sediment samples were incubated for up to 16 h. The transformation ratio of EMB to DES represented between 0.16 and 0.39% of EMB; values are lower than what has been observed in fish tissue. Data suggest that DES is generated through both abiotic (tested after autoclaving marine sediments) and biological processes. Further work on freshly sampled marine sediments with EMB deposits, different organic regimes, and a detailed assessment of active bacterial communities are necessary to better evaluate the EMB to DES rate of transformation around aquaculture sites.

[Anesthesia of the New Zealand rabbit using the the combination of tiletamine-zolazepam and ketamine-midazolam with or without xylazine]. / Anesthésie du lapin de Nouvelle-Zélande utilisant les combinaisons tilétamine-zolazépam et kétamine-midazolam avec ou sans xylazine.

In this study, anesthesia levels obtained with tiletamine-zolazepam (TZ) and ketamine-midazolam (KM) with or without xylazine (X) were compared in rabbits. Reflexes (corneal, palpebral and withdrawal), blood parameters (PaO2, PaCO2, pH and ions HCO3-), cardiovascular function (heart rate and mean arterial blood pressure) and body temperature were evaluated before and after the injections of the anesthetic combination in the same rabbits (n = 10). With KM and TZ, no suppression of reflexes occurred. The body temperature and pH decreased and HCO3- increased similarly to KMX et TZX. Some physiological and blood parameters were less (PAM, PaCO2) and not (PaO2) affected comparatively to KMX et TZX. These protocols were of short duration of action and did not offer any anesthesia or analgesia. Therefore, their utilization should be restricted to short procedures where no painful manipulations are performed. Ketamine-midazolam-xylazine and tiletamine-zolazepam-xylazine on the other hand are indicated for interventions that require anesthesia. With these combinations, all reflexes were absent for 30-45 and 60-90 min following injections of KMX et TZX, respectively. However, these combinations induce cardiac depression, as well as a decrease of all measured blood parameters and body temperature and a reduction of PaO2. Supplementation with oxygen is recommended with the introduction of xylazine in the protocol.

Role of specific apoptotic pathways in the restoration of paclitaxel-induced apoptosis by valspodar in doxorubicin-resistant MCF-7 breast cancer cells.

Paclitaxel (Taxol) kills tumor cells by inducing both cellular necrosis and apoptosis. A major impediment to paclitaxel cytotoxicity is the establishment of multidrug resistance whereby exposure to one chemotherapeutic agent results in cross-resistance to a wide variety of other drugs. For example, selection of MCF-7 breast cancer cells for resistance to doxorubicin (MCF-7ADR cells) results in cross-resistance to paclitaxel. This appears to involve the overexpression of the drug transporter P-glycoprotein which can efflux both drugs from tumor cells. However, MCF-7ADR cells possess a deletion mutation in p53 and have considerably reduced levels of the Fas receptor, Fas ligand, caspase-2, caspase-6, and caspase-8, suggesting that paclitaxel resistance may also stem from a bona fide block in paclitaxel-induced apoptosis in these cells. To address this issue, we examined the ability of the P-glycoprotein inhibitor valspodar to restore paclitaxel accumulation, paclitaxel cytotoxicity, and paclitaxel-induced apoptosis. Compared to drug sensitive MCF-7 cells, MCF-7ADR cells accumulated >6-fold less paclitaxel, were approximately 100-fold more resistant to killing by the drug, and were highly resistant to paclitaxel-induced apoptosis. In contrast, MCF-7ADR cells pretreated with valspodar were indistinguishable from drug-sensitive cells in their ability to accumulate paclitaxel, in their chemosensitivity to the drug, and in their ability to undergo paclitaxel-induced apoptosis. Valspodar, by itself, did not affect these parameters. This suggests that the enhancement of paclitaxel toxicity in MCF-7ADR cells involves a restoration of apoptosis and not solely through enhanced drug-induced necrosis. Morever, it appears that changes in the levels/activity of p53, the Fas receptor, Fas ligand, caspase-2, caspase-6, or caspase-8 activity have little effect on paclitaxel-induced cytotoxicity and apoptosis in human breast cancer cells.

A pathophysiological study of abdominal organs following intraperitoneal injections of chloral hydrate in rats: comparison between two anaesthesia protocols.

Chloral hydrate (CH) is used as an anaesthetic agent in laboratory rats. Side effects occurring with high concentrations have mainly occurred in abdominal organs. The objective of the present study was to minimize these side effects following intraperitoneal administration of CH using lower concentrations. Animals were evaluated using different procedures including a general necropsy, intraperitoneal white cell counts, histology and duodenal peristalsis and acetylcholine-induced contractions. Results clearly show that lower concentrations of CH while keeping the same anaesthetic dose (400 mg/kg) will minimize the irritancy of CH on abdominal organs while providing the same level of anaesthesia.

Comparison of ketoprofen and carprofen administered prior to orthopedic surgery for control of postoperative pain in dogs.

OBJECTIVE: To compare analgesic and adverse effects of ketoprofen and carprofen when used to control pain associated with elective orthopedic surgeries in dogs. DESIGN: Prospective randomized clinical trial. ANIMALS: 93 client-owned dogs: 46 undergoing reconstruction of the cranial cruciate ligament, 47 undergoing femoral head and neck excision, and 15 control dogs anesthetized for radiographic procedures. PROCEDURE: Dogs undergoing surgery were randomly given ketoprofen, carprofen, or saline (0.9% NaCl) solution, SC, prior to surgery. Pain score and serum cortisol concentration were recorded for 12 hours after surgery for all dogs. When pain score was > or = 7, oxymorphone was administered i.m. Bleeding time was measured prior to and during surgery. RESULTS: The proportion of dogs that required oxymorphone was significantly higher for the carprofen and placebo groups than for the ketoprofen group. Pain score for the placebo group was significantly higher than for the ketoprofen and carprofen groups, 2, 8, and 9 hours after surgery. Cortisol concentration was significantly higher for the placebo group than for the carprofen group at 4 and 6 hours after surgery. Significant differences were not detected between ketoprofen and carprofen groups with respect to pain score and cortisol concentration. Bleeding time was significantly longer for the ketoprofen group than for the other groups during surgery. One dog treated with ketoprofen developed a hematoma at the surgical site. CONCLUSIONS AND CLINICAL RELEVANCE: Ketoprofen and carprofen given prior to surgery were effective for postoperative pain relief in dogs. However, ketoprofen should not be used when noncompressible bleeding may be a problem.

Descriptive study to compare patient recall of information: nurse-taught versus video supplement.

An important goal in oncology nursing is to provide outpatients receiving chemotherapy with adequate information about their treatment so they will be able to cope with treatment reactions and make appropriate decisions about seeking early medical attention when potentially serious side-effects occur. The purpose of the present study was to evaluate patient teaching strategies at one cancer centre. A comparative descriptive study design was employed. A group of patients receiving one-to-one nurse/patient teaching was compared to a group of patients receiving one-to-one nurse/patient teaching plus a take-home instructional chemotherapy video. The patient groups were compared with respect to: a) level of recall of chemotherapy information; b) the sources of information used; and c) preferred information sources. When the mean scores achieved on the chemotherapy knowledge questionnaire were compared, no statistically significant differences were found between the two groups. In fact, both groups showed a "high" level of information recall. Both patient groups reported using a variety of information sources to learn about their chemotherapy, however, for both groups the preferred sources of information were their direct health care providers. The results of the study raise interesting issues about the feasibility of developing "high-tech" patient education strategies.

Effects of buprenorphine on cardiovascular and pulmonary function in clinically normal horses and horses with chronic obstructive pulmonary disease.

OBJECTIVES: To evaluate the cardiovascular and respiratory effects of buprenorphine administered intravenously in clinically normal horses and horses with chronic obstructive pulmonary disease (COPD). ANIMALS: 5 clinically normal horses and 5 horses with COPD that were in partial clinical remission (period A) or were having an acute attack of airway obstruction (period B). PROCEDURES: Pulmonary function testing, arterial blood gas analysis, and arterial blood pressure measurements were performed before and after a single intravenous bolus of buprenorphine (3 microg/kg of body weight). Respiratory rate (f), tidal volume (VT), expiratory-to-inspiratory time ratio (TE/TI), minute expiratory ventilation (VE), maximal change in transpulmonary pressure (deltaPL), dynamic compliance (Cdyn), and pulmonary resistance (RL) were calculated with a pulmonary function computer. Heart rate (HR) and systolic (SABP), diastolic (DABP), and mean arterial blood pressures (MABP) were measured. RESULTS: At baseline, COPD horses in period A had decreased Cdyn and increased f, VE, PL, and HR, whereas COPD horses in period B had decreased TE/TI and Cdyn, arterial blood pH, and PO2, and increased f, VE, deltaPL, and RL, compared with clinically normal horses. After drug administration, SABP, DABP, and MABP increased in all horses, f and VE increased in clinically normal horses, and PaO2 decreased within 60 minutes in horses with COPD. CONCLUSION AND CLINICAL RELEVANCE: Buprenorphine can induce excitement in unsedated horses or horses that do not have signs of pain, but does not seem to induce severe respiratory depression or adverse cardiovascular effects in clinically normal horses or those with COPD.

Comparison of ketoprofen, oxymorphone hydrochloride, and butorphanol in the treatment of postoperative pain in dogs.

OBJECTIVE: To compare analgesic effects of ketoprofen, oxymorphone hydrochloride, and butorphanol when used to control postoperative pain associated with elective orthopedic surgery in dogs. DESIGN: Prospective randomized clinical trial. ANIMALS: 70 dogs undergoing orthopedic surgery on a hind limb. PROCEDURE: Dogs were randomly assigned to 1 of 4 postoperative analgesic treatment groups: ketoprofen alone, oxymorphone alone, butorphanol alone, or ketoprofen-oxymorphone. Drugs were given IM at the end of anesthesia. Pain score, sedation score, arterial blood pressures, arterial blood gas partial pressures, and plasma cortisol concentration were measured for 12 hours after surgery. If the pain score was > or = 9, supplemental oxymorphone was administered IM. RESULTS: The proportion of dogs that did not require supplemental treatment with oxymorphone was significantly higher for the ketoprofen alone and ketoprofen-oxymorphone groups than for the oxymorphone alone group. During the first hour after surgery, pain score was lower for oxymorphone alone and ketoprofen-oxymorphone groups than for ketoprofen or butorphanol alone groups. Significant differences were not detected among groups in regard to pain score 2 and 3 hours after surgery or in regard to arterial blood pressures at any time. From 4 to 12 hours after surgery, pain score was significantly lower for the ketoprofen alone group than for other groups. Plasma cortisol concentration was significantly higher for the oxymorphone alone group 6 and 8 hours after surgery, compared with other groups. CLINICAL IMPLICATIONS: Except during the first hour after surgery, dogs given ketoprofen alone after elective orthopedic surgery had a greater level of, and longer-lasting, analgesia than did dogs given oxymorphone or butorphanol alone.

[Use of a mix of lidocaine and butorphanol as a caudal epidural anesthesia in a mare]. / Utilisation du mélange lidocaïne-butorphanol en anesthésie épidurale caudale chez la jument.

Loss of rear motor control is the main limiting factor in the use of caudal epidural anesthesia in the horse. In man and laboratory animals, a small dose of an opiate combined with a local anesthetic enhances analgesia without impairing motor function. Thus, the amount of local anesthetic administered may be reduced. Butorphanol is an opiate widely used in horses. It has a good margin of safety and few cardiorespiratory effects. The effects of lidocaine (0.25 mg/kg) and lidocaine-butorphanol (0.25 mg/kg, and 0.04 mg/kg, respectively) were compared in 2 groups of 5 healthy unsedated mares. Horses in each group received either lidocaine or lidocaine-butorphanol in saline solution for a total volume of 0.0165 mg/kg. Epidural injection was performed at the first coccygeal interspace. Each mare was used only once. Cutaneous analgesia was assessed by a response to a pin prick; and visceral analgesia was assessed by response to a noxious stimulus applied to the urethra. Heart rate, respiratory rate, and arterial blood pressure were also measured. Analysis of the results showed an increase in duration of both cutaneous and visceral analgesia in the mares given lidocaine-butorphanol. Cutaneous analgesia increased from 36 +/- 13 to 150 +/- 21 min and visceral analgesia increased from 22 +/- 10 to 162 +/- 16 min. A cranial extension of the cutaneous analgesia was also observed. Cardiorespiratory depression or signs of excitation were not observed. However, these mares demonstrated peculiar walking in the hind limbs, not associated with signs of ataxia or hyperkinesia.

Evaluation of analgesia and cardiorespiratory effects of epidurally administered butorphanol in isoflurane-anesthetized dogs.

OBJECTIVE: To determine variations in minimal alveolar concentration (MAC) of isoflurane and analgesic and cardiorespiratory effects of lumbosacral epidural administration of 0.25 mg of butorphanol/kg of body weight in dogs. ANIMALS: 16 healthy male dogs. PROCEDURE: Dogs were anesthetized with isoflurane alone. Eight dogs received butorphanol (group B) and the others an equal volume of isotonic saline solution (group S) administered by a catheter inserted in the lumbosacral epidural space. Isoflurane MAC was determined before and 30 minutes after the epidural injection, along with noxious stimulation to the fore- and bind limbs. Cardiorespiratory variables were recorded prior to and until 120 minutes after epidural administration. At that time, isoflurane anesthesia was ended, and nociception (toe pinch and pin-prick responses) was evaluated for 7 hours. Dogs were observed for 3 days to determine presence of neurologic side effects. RESULTS: For group-B dogs, isoflurane MAC decreased by 31 +/- 8.6% after butorphanol was administered Cutaneous insensitivity (to pin-prick nociceptive test) persisted for 3 hours after the end of isoflurane anesthesia in group-B dogs. No response was observed to toe pinch stimulation for 80 minutes after anesthesia. CONCLUSIONS: Epidural administration of 0.25 mg of butorphanol/kg in dogs was safe; minimal cardiorespiratory and no neurologic side effects were observed, and analgesia and an isoflurane-sparing effect were apparent. CLINICAL RELEVANCE: The short duration of action of epidurally administered butorphanol limits its value for clinical practice.

Pharmacokinetics of epidural butorphanol in isoflurane-anaesthetized dogs.

Sixteen healthy male dogs were used at random in this protocol. The dogs were anaesthetized with isoflurane in oxygen. Eight of the dogs received 0.25 mg/kg of butorphanol (group B) and the others an equal volume of isotonic saline (group S) administered by a catheter inserted in the lumbosacral epidural space. Butorphanol concentrations in plasma and cerebrospinal fluid (CSF) were measured using high-performance liquid chromatography with electrochemical detection. Maximum concentration of butorphanol and time to obtain this concentration were 42.28 ng/mL at 13.88 min in blood, and 18.03 ng/mL at 30 min in CSF. Volume of distribution, clearance, mean distribution and elimination half-lives were respectively 4.39 L/kg, 2.02 L/h.kg, 16.5 min and 189.1 min. Mean isoflurane minimal alveolar concentration values for group B obtained following hind- or forelimb stimulation decreased by 31% after epidural butorphanol. Cutaneous analgesia (to pin-prick test) persisted for 3 h after the end of isoflurane anaesthesia in group B and was in correlation with the plasmatic analgesic dose of butorphanol (9 ng/mL). These results suggested that analgesia was predominantly obtained by action of butorphanol on the supraspinal structures following its vascular systemic absorption.

Effects of a combination of detomidine and butorphanol on respiratory function in horses with or without chronic obstructive pulmonary disease.

OBJECTIVE: To evaluate the effects of detomidine and butorphanol in combination on respiratory function in horses and to determine whether these effects are more severe in horses with pre-existing respiratory dysfunction, DESIGN: Pulmonary function testing and arterial blood gas analyses were performed before and after administration of a combination of detomidine (10 micrograms/kg of body weight, i.v.) and butorphanol (20 micrograms/kg, i.v.). ANIMALS: 5 horses with chronic obstructive pulmonary disease and 5 horses free of respiratory disease (controls). PROCEDURES: Flow rates were obtained from a pneumotachograph attached to a face mask, and esophageal pressure was measured with a catheter placed in the distal third of the esophagus. Respiratory rate, tidal volume (VT), minute ventilation (VE), maximal change in transpulmonary pressure, pulmonary resistance, and dynamic compliance were calculated by use of a pulmonary function computer. Arterial blood was collected from the transverse facial artery, and blood gas partial pressures were measured with an automated blood gas analyzer. RESULTS: The combination of detomidine and butorphanol caused significant changes with time in respiratory rate, VT, VE, PaO2, and PaCO2. Changes with time in VT, VE, and maximal change in transpulmonary pressure were significantly different between groups. CONCLUSION: The combination of detomidine and butorphanol affects respiratory function in horses, and the observed changes are affected by the presence of pre-existing respiratory dysfunction. CLINICAL RELEVANCE: Changes in respiratory function after administration of a combination of detomidine and butorphanol are not necessarily more severe in horses with pre-existing respiratory dysfunction.

[Intravenous anesthesia in the horse: comparison of xylazine-ketamine and xylazine-tiletamine-zolazepam combinations]. / L'anesthésie intraveineuse chez le cheval: comparaison des combinaisons xylazine-kétamine et xylazine-tilétamine-zolazépam.

Intravenous anesthesia in the horse: Comparison of xylazine-ketamine and xylaxine-tiletamine-zolazepam combinations. Six healthy adult horses were anesthetized twice at random with following intravenous combinations: 1.1 mg/kg of body weight (BW) of xylazine followed by 2.2 mg/kg BW of ketamine (X-K) and 1.1 mg/kg BW of xylazine followed by 1.65 mg/kg BW of tiletamine-zolazepam (X-TZ). The modifications of some cardiorespiratory parameters and the duration of anesthesia were evaluated and compared for the 2 protocols used. Few significant differences were observed between the 2 protocols in regard to the cardiorespiratory parameters measured. The respiratory rate was lower (7 breaths per minute) and the heart rate was higher (34 beats per minute) with the X-TZ combination. The duration of anesthesia with this technique was 33 +/- 3 minutes (X +/- Sx) and longer than with X-K (18 +/- minutes (X +/- Sx)). Superficial analgesia lasted 14,5 +/- 3 minutes with the X-K combination and 31,7 +/- 3,2 minutes for the X-TZ combination. The 2 protocols are associated with a reduction of PaO2.

Anesthetic management of the trauma patient.

The key to safe anesthesia of a trauma patient is preoperative stabilization. It minimizes the anesthesia risk and allows proper choices of anesthetic drugs. Adequate monitoring throughout anesthesia allows rapid and adequate therapeutic intervention. Proper control of upper airway and support of physiologic functions will enhance the chances of the patient to survive anesthesia.

Lack of role for nitric oxide (NO) in the selective destabilization of endothelial NO synthase mRNA by tumor necrosis factor-alpha.

The constitutive expression of endothelial nitric oxide (NO) synthase (cNOS) is essential for the physiological regulation of vascular tone and structure. The mechanism of downregulation of steady state cNOS mRNA in human umbilical vein endothelial cells exposed to tumor necrosis factor-alpha (TNF-alpha) was investigated by using Northern blot analysis of total cellular RNA. TNF-alpha produced a dose- and time-dependent decrease in cNOS mRNA expression that was near maximal at 10 U/mL and 6 hours of exposure, respectively. In contrast, steady state expression of endothelin-1 and plasminogen activator inhibitor-1 (PAI-1) mRNA was upregulated by TNF-alpha. The pharmacological generation of NO using sodium nitroprusside (10 mumol/L) and S-nitroso-acetylpenicillamine (100 to 400 mumol/L) had no effect on cNOS mRNA levels, and TNF-alpha-induced downregulation of cNOS was not prevented by coincubation with the inhibitors of NO synthesis N omega-nitro-L-arginine methyl ester (1 mmol/L) and NG-monomethyl L-arginine (10 mmol/L). Under control conditions, cNOS and PAI-1 mRNA were stable after treatment with actinomycin D for periods greater than 24 hours, whereas endothelin-1 message was rapidly degraded (half-life, < 1 hour). Pretreatment with TNF-alpha (30 U/mL) selectively reduced that half-life of cNOS mRNA to less than 12 hours without altering the stability of PAI-1 message. TNF-alpha-induced destabilization of cNOS mRNA could be partially prevented by coincubation with cycloheximide (1 mumol/L) but was not reproduced by addition of sodium nitroprusside.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of cyclic nucleotides in the regulation of endothelin-1 production by human endothelial cells.

The regulation of endothelin-1 (ET-1) production by endothelial cells is likely of crucial physiological importance in the maintenance of vascular homeostasis. The aim of the present study was to explore the possible role of cyclic nucleotides in the control of ET-1 production in human umbilical vein endothelial cells (HUVEC). ET-1 release was determined by measuring levels of immunoreactive ET-1 in HUVEC-conditioned media after 6-h incubations. In the presence of 10% fetal calf serum (FCS) there was a threefold increase in ET-1 release compared with serum-free conditions (1.96 +/- 0.17 vs. 0.56 +/- 0.06 pg/micrograms protein), respectively. Inhibition of protein kinase (PK) C using staurosporine (10 nM) reduced basal ET-1 release by approximately 50% and completely prevented the response to FCS. In contrast, the addition of other PK inhibitors had little effect on basal or serum-stimulated ET-1 release at the concentrations used. N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP) produced significant alterations in ET-1 release depending on the basal level of production. Under serum-free conditions of low basal ET-1 production, DBcAMP increased ET-1 release by 68 +/- 22% but only at the highest concentration studied (1 mM). The dose-response relationship for DBcAMP was potentiated by KT-5720 (0.1 microM), an inhibitor of PKA, with a significant shift to 10-fold lower concentrations, whereas it was blocked by KT-5823 (4 microM), which can inhibit PKG.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemorrhagic myelomalacia following general anesthesia in a horse.

An 18-month-old male Belgian horse was anesthetized and placed in dorsal recumbency for cryptorchidectomy. Xylazine was used for sedation and guaifenesin with thiamylal for induction of anesthesia. A surgical plane of anesthesia was maintained with halothane. During anesthesia, second-degree atrio-ventricular blocks, hypoventilation and a 1-minute duration rise of mean arterial pressure (80 to 130 mm Hg) occurred. Total anesthesia time was 1 hour. On recovery from anesthesia, the horse exhibited flaccid paralysis of the hind limbs and was only able to elevate himself to a dog sitting position. The horse was humanely euthanized 22 hours postoperatively due to a lack of improvement in clinical signs. Hemorrhagic poliomyelomalacic lesions of the spinal cord were observed on histopathological examination of the spinal cord.

Mechanisms of glomerular injury in experimental immune nephritis. II. Effect of a platelet activating factor receptor antagonist in an autologous nephritis model.

The role of Platelet Activating Factor (PAF) in experimental immune glomerulonephritis was assessed by administering the specific PAF receptor antagonist CV-3988 to inbred LEW rats with the Accelerated Autologous Nephrotoxic Serum Nephritis (AA-NTSN). Intravenous administration of CV-3988 caused a marked and sustained reduction in albuminuria and renal histopathological changes. Conversely, although CV-3988 appeared to modulate the fall in glomerular filtration rate (GFR) in the AA-NTSN, this trend was not statistically significant. Renal glomeruli isolated on day 1 after nephritis induction spontaneously released 16.9 +/- 2.2 ng of PAF per 200 glomeruli, while in glomeruli of healthy rats this secretion was virtually undetectable. The administration of CV-3988 to rats with AA-NTSN did not affect the following: binding of intravenously injected sheep anti-rat glomerular basement membrane (GBM) antibody; levels of autologous antibody to sheep immunoglobulin G; the functional integrity of circulating neutrophils. We conclude that local PAF generation and release is intimately linked with the pathogenesis of glomerular injury in this form of immune disease.