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Biomedical subjects

H J Sugerman

Publications and source records attributed to H J Sugerman.

At least 109 records · Page 6Linked to original sources
PubMed1992

The neutrophil respiratory burst and tissue injury in septic acute lung injury: the effect of cyclooxygenase inhibition in swine.

Cyclooxygenase inhibition has been proposed as treatment for sepsis-induced acute lung injury. However, the mechanism of protection offered by the cyclooxygenase inhibitor ibuprofen is not well understood. To elucidate this mechanism, the effects of ibuprofen on the neutrophil respiratory burst and alveolar-capillary membrane leak were studied. Anesthetized swine (15 to 25 kg) were intubated and mechanically ventilated (fraction of inspired oxygen, 0.5). Control animals (n = 5) received a sham infusion of 0.9% NaCl, animals with sepsis (n = 10) received a 1-hour infusion of live Pseudomonas aeruginosa (5 x 10(8) colony-forming units/ml at 0.3 ml/20 kg/hr), and treated animals (ibuprofen-treated control animals [n = 4] or ibuprofen-treated animals with sepsis [n = 9]) received ibuprofen (12.5 mg/kg at 0 and 120 minutes). All animals were studied for 300 minutes. Neutrophils were isolated at 0, 60, and 300 minutes. Neutrophil superoxide anion production (O2-) was assessed in a kinetic fashion (in nanomoles per minute) by superoxide dismutase-inhibitable cytochrome C reduction (phorbol myristate acetate stimulation). Bronchoalveolar lavage protein estimation (0 and 300 minutes) and extravascular lung water (double indicator dilution) were performed to assess alveolar-capillary membrane leak. Ibuprofen significantly attenuated sepsis-enhanced maximum neutrophil generation of O2- (6.0 +/- 0.5 nmol/min for animals with sepsis, 300 minutes, vs 4.1 +/- 0.5 nmol/min for ibuprofen-treated animals, with sepsis, 300 minutes; p less than 0.05), indicating an in vivo down-regulatory effect on neutrophil oxidant generation. Ibuprofen also prevented increased airspace bronchoalveolar lavage protein and extravascular lung water accumulation, suggesting a protective effect on the alveolar-capillary membrane. This protective effect of ibuprofen in acute lung injury may be through a decreased neutrophil respiratory burst.

Acute Disease↗
PubMed1992

Neutrophil short-lived oxidant production: enhancement following onset of sepsis-induced lung injury.

Generation of superoxide anion (O2-) by activated neutrophils (PMN) is implicated in the pathogenesis of endothelial cell injury in sepsis. To quantitate this phenomenon we studied the kinetics of O2- production by PMN following in vivo and in vitro exposure to Pseudomonas aeruginosa. PMN were isolated from young swine before and after a 1-hr infusion with 5 x 10(8) organisms/ml at 0.3 ml/20 kg/min. Baseline PMN were studied in an in vitro system where 1 x 10(6) porcine PMN were incubated with live Pseudomonas for 1 hr at 37 degrees C. Neutrophils from septic pigs exhibited a significantly increased (P less than 0.05) initial rate of O2 production, which was 125% greater at 2 min following initial stimulation than saline controls (P less than 0.001). Neutrophils exposed in vitro displayed a similar enhancement of the rate of O2- production; however, the rate was 3.6 times greater than that noted in vivo. The in vivo change in PMN oxidant generation was associated with a rise in both extravascular lung water (EVLW) and increased bronchoalveolar lavage protein (BAL-P) content. These data suggest that sepsis-induced acute lung injury is accompanied by "priming" of circulating PMN; however, important factors are present in the circulation in sepsis that serve to attenuate the damaging potential of PMN oxidant species.

Animals↗
PubMed1992

Calcium in human gallbladder bile.

Biliary calcium is believed to be of great importance in gallstone pathogenesis. These studies were therefore performed to determine if quantitative and/or qualitative differences in calcium are present in gallbladder bile from patients with and without gallstones. Bile was obtained by direct gallbladder aspiration from 68 obese patients undergoing elective gastric bypass surgery. Forty-five patients had no evidence of gallstones or sludge, 18 had cholesterol gallstones, and five had black pigment stones. Gallbladder bile was also obtained from 27 nonobese patients undergoing elective cholecystectomy (19 cholesterol; eight black pigment gallstones). For all patients, total calcium ranged from 1.50 to 16.44 mmol/L (mean: 6.05 +/- 0.31 mmol/L); free Ca++ ion ranged from 0.53 to 2.83 mmol/L (mean: 1.28 +/- 0.05 mmol/L). Considerable overlap was observed between obese and nonobese subjects and between patients with and without gallstones. For all patient groups, calcium, Ca++, and bound calcium increased linearly with increasing concentrations of bile salt. No significant differences in the slopes of these relationships were observed with obesity or gallstones. In contrast, free Ca++ ion was greater in gallbladder bile from gallstone patient groups throughout the entire range of bile salt. We hypothesize that this observed increase in Ca++ resulted from increased Gibbs-Donnan forces and excess gallbladder mucin present within the gallbladder bile of patients with gallstones.

Adolescent↗
PubMed1992

Stomal complications of gastric bypass: incidence and outcome of therapy.

Gastric bypass is an effective treatment for morbid obesity. However, it is sometimes complicated by stenosis or ulceration of the gastrojejunal anastomosis. Stomal ulceration and stenosis developed in, respectively, 12.5% and 12% of 191 patients who underwent gastric bypass. Only 3% had both complications simultaneously. The risk of developing either complication was highest in the first 2 months after surgery. Stomal stenosis responded to endoscopic dilation in all instances, and appears to be a safe and effective method of treating this problem following gastric bypass. Stomal ulceration healed with an H2 blocker and sucralfate administration in all but one patient. Postoperative weight loss was similar in patients with or without stomal stenosis or ulceration. We conclude that, although stomal complications occur in about 20% of all patients undergoing gastric bypass, they can almost always be managed by conservative therapy.

Catheterization↗
PubMed1991

CD18 adhesion receptors, tumor necrosis factor, and neutropenia during septic lung injury.

Sequestration of neutrophils (PMNs) in the pulmonary microvasculature and associated neutropenia are characteristic features of experimental models of septic lung injury. The etiology of altered PMN kinetics during septic lung injury is uncertain, but may be partially due to increased adhesiveness of activated PMNs to pulmonary endothelium. This study examines the relationship between the expression of PMN CD18 adhesion receptors, the evolving neutropenia, and plasma tumor necrosis factor (TNF) activity in a porcine model of septic lung injury. Acute lung injury was induced by infusion of live Pseudomonas aeruginosa (5 x 10(8) CFU/ml at 0.3 ml/20 kg/min) for 60 min (Group Ps, n = 6). Control animals (Group C, n = 3) received a 60-min infusion of sterile 0.9% saline. CD18 expression of circulating PMNs was measured by quantitative immunofluorescent flow cytometry. Plasma TNF activity was measured by L929 fibroblast cytolytic assay. Group Ps developed a significant neutropenia by 30 min (14.9 +/- 2.5 vs 23.4 +/- 3.3 x 10(3) cells/microliter at baseline, P less than 0.05, ANOVA) with circulating neutrophils exhibiting significantly increased CD18 expression by 60 min (6.34 +/- 0.72 vs 5.01 +/- 0.52 equivalent soluble fluorescence molecules (ESFM) x 10(3) at baseline, P less than 0.05, ANOVA). Group Ps demonstrated a significant increase in plasma TNF activity by 30 min (2.5 +/- 0.9 vs 0.7 +/- 0.3 U/ml at baseline). There was no significant change in PMN count, PMN CD18 expression, or plasma TNF activity in Group C. In complimentary in vitro studies, porcine PMNs stimulated with recombinant human TNF-alpha (n = 5) demonstrated a time- and dose-dependent increase in CD18 expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Platelet-activating factor in porcine Pseudomonas acute lung injury.

We investigated the role of platelet-activating factor (PAF) in acute septic lung injury by examining the effects of the selective PAF antagonist SRI 63-675 and by measuring PAF in lung tissue in the porcine model. Four groups of pigs (15-25 kg) were studied: saline control (C, n = 5); Pseudomonas (Ps, n = 9), given 5 x 10(8) CFU/ml at 0.3 ml/20 kg/min intravenously over 1 hr; SRI (n = 3), given SRI 63-675 in a 40 mg/kg bolus; and SRI + Ps (n = 5). Ps infusion produced a fulminant lung injury characterized by a threefold increase in pulmonary arterial pressure at 30 min and persistent pulmonary hypertension (P less than 0.05 vs C), a significant (P less than 0.05 vs C) decrease in arterial oxygen tension (PaO2) from 60 min, a significant (P less than 0.05 vs C) increase in extravascular lung water (EVLW) from 120 min, and a significant (P less than 0.05 vs C) increase in albumin flux determined scintigraphically as slope index at 150-180 min. Systemic arterial pressure and cardiac index (CI) decreased significantly (P less than 0.05) in the Ps group vs C at 60 and 180 min, respectively. Bolus injection of SRI 63-675 at the time of Ps infusion blocked the early pulmonary hypertension, attenuated the early and late fall in PaO2, ameliorated the increase in EVLW, and prevented the late (150-180 min) increase in albumin flux. SRI 63-675 had minimal effects on Ps-induced hypotension or alterations in CI.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1991

Stapled ileoanal anastomosis for ulcerative colitis and familial polyposis without a temporary diverting ileostomy.

Between March 1989 and August 1990, we performed 21 stapled J pouch ileonal procedures (20 ulcerative colitis [UC], 1 familial polyposis [FP]) without an ileostomy in 19, of whom 13 were taking prednisone and eight underwent semi-emergent surgery for uncontrollable bleeding. During the same time, an additional four patients required a standard ileonal procedure. The results of anal manometry and clinical function were compared to 25 patients who had previously undergone mucosal stripping and a sutured J pouch ileoanal anastomoses with a temporary diverting ileostomy between October 1982 and August 1990. During this same time period, an additional 19 patients underwent an anti-peristaltic reversed J pouch and 18 an S pouch, for a total of 83 ileoanal procedures. The reversed J pouch had a lower stool frequency than a standard J pouch but had an unacceptable incidence of complications and problems with pouch emptying. The S pouch had a stool frequency similar to the standard J pouch but provided greater length in patients with a short mesentery. Stapled J pouch ileoanal patients had a better (p less than 0.02) maximum and sphincter resting pressure (46 +/- 11 versus 34 +/- 12 mmHg), fewer (p less than 0.05) night-time accidents (22% versus 68%), daytime (17% versus 55%) or night-time (28 versus 61%) spotting, or use of a protective pad at night (11% versus 42%) than nonstapled J pouch ileoanal patients. Stool frequency was similar in the two groups. All but one UC patient had residual disease at the anastomosis. Anal mucosa between the dentate line and stapled anastomosis was 1.8 +/- 1.3 cm (range, 0 to 3.5 cm). Complications in the nonstapled J pouch group included 4 pouches excised (2 for complications, 2 for excessive stool frequency), 1 pelvic abscess, 2 stenosis requiring dilation under anesthesia, 1 enterocutaneous fistula after ileostomy closure, 1 ileostomy site hernia, and 2 small bowel obstructions. Of the 65 patients who underwent ileostomy closure in the entire series, 8 (12%) developed a complication requiring surgical intervention. Complications in the stapled group included 1 anastomotic leak, 1 pouch leak, and 1 pelvic abscess. Patients were managed successfully with drainage (all 3) and diverting ileostomy (1). One patient developed stenosis requiring dilation under anesthesia. The stapled J pouch ileoanal anastomosis is a simpler, safer procedure with less tension than a standard handsewn J pouch but leaves a very small cuff of residual disease. It provides significantly better stool control and may obviate the need for an ileostomy with its complications.

Anal Canal↗
PubMed1991

Delayed cyclo-oxygenase blockade reduces the neutrophil respiratory burst and plasma tumor necrosis factor levels in sepsis-induced acute lung injury.

Ibuprofen pretreatment attenuates the enhanced neutrophil (PMN) respiratory burst and reduces increased plasma tumor necrosis factor (TNF) activity in porcine sepsis-induced acute lung injury (ALI). These septic responses have been linked to increased alveolar-capillary membrane (ACM) permeability. This study was designed to establish whether delayed ibuprofen treatment would have the same effect and to examine the relationship between PMN oxidant generation and TNF. Three groups of anesthetized, ventilated pigs (15-25 kg) were used. Group Ps received Pseudomonas aeruginosa (5 x 10(8) CFU/mL at 0.3 mL/20 kg/min) for one hour IV; The control group (Con) received 0.9% NaCl. Group D-Ibu received ibuprofen 12.5 mg/kg as a delayed bolus at 30 minutes and again at 120 minutes after Ps. Protein (BAL-P, microgram/mL) in harvested bronchoalveolar lavage fluid and extravascular lung water (EVLW, mL/kg) were used to estimate the integrity of the ACM. Superoxide anion (O2-) generation (ferricytochrome c reduction) from circulating PMNs and plasma TNF activity (L929 fibroblast bioassay) were measured. The EVLW increased significantly (p less than 0.05), as did BAL-P (p less than 0.01), in the P. aeruginosa-treated animals at 300 minutes. These increases were abolished in Group D-Ibu: EVLW, 6.6 +/- 1.0 baseline vs. 14.6 +/- 2.6 Ps 300 vs. 6.8 +/- 0.9 D-Ibu 300; BAL-P, 175 +/- 28 baseline vs. 984 +/- 186 Ps 300 vs. 284 +/- 42.8 D-Ibu 300. Both enhanced PMN oxidant activity and increased plasma TNF activity were significantly attenuated by delayed ibuprofen treatment. These data support the efficacy of the nonsteroidal anti-inflammatory drug, ibuprofen, when used after the onset of a septic stimulus.

Animals↗
PubMed1991

Ibuprofen attenuates plasma tumor necrosis factor activity during sepsis-induced acute lung injury.

Plasma tumor necrosis factor (TNF) activity, cardiac index, extravascular lung water, systemic and pulmonary arterial pressures, pulmonary vascular resistance index, and arterial PO2 were monitored for 300 min in four groups of anesthetized pigs: saline-infused animals (n = 5), saline-infused animals given ibuprofen (12.5 mg/kg iv) at 0 and 120 min (n = 4), animals infused for 60 min with live Pseudomonas aeruginosa (Ps, 5 x 10(8) organisms/ml at 0.3 ml.20 kg-1.min-1, n = 6), and animals infused for 60 min with Ps plus ibuprofen administered at 0 and 120 min (n = 4). Infusion of Ps induced significant elevations (greater than 4-fold increase in units/ml of TNF by 60 min, P less than 0.05) in plasma TNF activity (L929 cytolysis assay) and alterations (P less than 0.05) in all hemodynamic and pulmonary parameters within 30-60 min. Ibuprofen administration in sepsis significantly decreased peak TNF activity by 2 units/ml and attenuated many of the physiological alterations due to sepsis. These results show that ibuprofen attenuates sepsis-induced injury and that alterations of acute septic insult are correlated with reduced plasma TNF activity in septic animals given ibuprofen.

Acute Disease↗
PubMed1991

Sepsis-induced lung injury and the effects of ibuprofen pretreatment. Analysis of early alveolar events via repetitive bronchoalveolar lavage.

Current knowledge of alveolar pathophysiology during early sepsis-induced acute lung injury (ALI) and the role of resident alveolar macrophages (AM) in mediating alveolar inflammatory events during sepsis is limited. Further, the effects of ibuprofen pretreatment upon alveolar pathophysiology and AM function during early sepsis-induced ALI is unclear. Utilizing repetitive bronchoalveolar lavage (BAL) in a porcine model of sepsis-induced ALI, we studied changes in alveolar cellular constituents, BAL protein content and molecular composition, and AM superoxide anion (O2-.) generation during early sepsis. The neutrophil percentage of recovered alveolar cells (17 +/- 8%, t = 300 min versus 2 +/- 1%, t = 0; p = 0.06) and the bronchoalveolar lavage total protein content (493 +/- 110 micrograms/ml, t = 300 min versus 109 +/- 18 micrograms/ml, t = 0; p less than 0.05) increased in septic animals. Increases in BAL fluid total protein were primarily due to low-molecular-weight plasma protein, indicating relative preservation of alveolar-capillary membrane size selectivity. Alveolar macrophages harvested following 300 min of sepsis generated significantly less O2-. following phorbol myristate acetate (PMA) stimulation compared to AM harvested at baseline. Ibuprofen pretreatment of septic animals completely blocked leakage of plasma proteins into the alveoli and attenuated neutrophil migration but did not prevent downregulation of AM O2-. generation. Increased alveolar-capillary membrane permeability, neutrophil migration into the alveoli, and downregulation of AM oxidant generation occur within hours of the onset of sepsis. Ibuprofen pretreatment significantly attenuates early sepsis-induced ALI without altering sepsis-induced AM dysfunction.

Animals↗
PubMed1991

Tumor necrosis factor. Alpha and beta subtypes appear in circulation during onset of sepsis-induced lung injury.

Tumor necrosis factor (TNF) may be involved in the pathogenesis of acute lung injury (ALI) associated with septicemia. Therefore, we measured plasma TNF activity during sepsis and development of lung injury in a porcine model of ALI. Plasma samples were obtained from anesthetized saline-infused control pigs (n = 10) and those infused for 1 h with live Pseudomonas aeruginosa (10(8) organisms/ml, 0.3 ml/20 kg/min) (n = 16). TNF activity was measured in plasma using the L929 fibroblast cytolytic assay. L929 cytotoxicity caused by TNF-alpha or TNF-beta was determined in plasma by measuring the cytotoxicity neutralized by TNF antisera. No significant TNF activity was detected in control pig plasma. In septic pigs, TNF activity appeared in plasma 15 min after onset of septicemia and remained elevated throughout the experiment (6.1 +/- 10.2% to 80.0 +/- 5.0%, 15 and 300 min, respectively). The appearance of pulmonary arterial hypertension, increased lung water, decreased lung compliance, and deteriorating gas exchange was correlated with the rise in plasma TNF activity, which reached a peak at 90 to 120 min in septic pigs. Our results provide evidence that both TNF subtypes are present in plasma during septicemia. Anti-TNF-alpha and anti-TNF-beta neutralized TNF activity in whole septic plasma at 15, 30, and 45 min after onset of septicemia, and the antibodies blocked TNF activity in serially diluted septic plasma at all time points up to 210 min of sepsis. TNF activity in septic plasma at 210 to 300 min was not neutralized entirely by TNF antisera.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Anti-CD18 antibody attenuates neutropenia and alveolar capillary-membrane injury during gram-negative sepsis.

Activated polymorphonuclear leukocytes (PMNs) are implicated in the pathogenesis of acute lung injury (ALI) associated with sepsis. Adhesion of activated PMNs to endothelial monolayers is mediated by the CD18 adhesion-receptor complex on the PMN cell surface. Monoclonal antibody 60.3 (MoAb 60.3) blocks CD18-dependent PMN-endothelial adhesion in vitro and in vivo. This study was designed to determine the role of CD18-dependent PMN adhesion in ALI associated with gram-negative sepsis. Anesthetized, ventilated (FiO2 0.5, positive end-expiratory pressure 5 cm H2O) pigs received sterile saline (control, n = 8) or live Pseudomonas aeruginosa, 5 x 10(8) colony-forming units/ml at 0.3 ml/20 kg/min (septic, n = 9) for 1 hour. A third group (n = 7) received MoAb 60.3, 2 mg/kg intravenously, 15 minutes before Pseudomonas infusion. Animals were studied for 300 minutes. MoAb 60.3 significantly (p less than 0.05) attenuated the neutropenia seen in sepsis (15 +/- 1 vs 6 +/- 1 x 10(3) PMNs/mm3 at 300 min). Alveolar-capillary membrane injury was assessed by bronchoalveolar-lavage protein content and extravascular lung water determination. MoAb 60.3 significantly (p less than 0.05) reduced BAL protein at 300 minutes (388 +/- 75 vs 1059 +/- 216 micrograms/ml in septic animals) and attenuated the increase in extravascular lung water to 240 minutes (7.1 +/- 2 vs 14.2 +/- 1.2 ml/kg in septic animals). Systemic hypotension, decreased cardiac index, pulmonary hypertension, and relative hypoxemia, all characteristic of this model, were not altered by MoAb 60.3. These data suggest that, in this model of septic ALI, neutropenia is, in part, CD18 dependent and that blocking CD18-dependent PMN adhesion protects the alveolar-capillary membrane independently of altered hemodynamic status.

Acute Disease↗
PubMed1991

Gallstone formation after rapid weight loss: a prospective study in patients undergoing gastric bypass surgery for treatment of morbid obesity.

The present study evaluated the incidence of gallstone formation in 105 morbidly obese patients undergoing rapid weight loss after proximal gastric bypass surgery. Intraoperative ultrasonography demonstrated gallstones in 20 (19%) and gallbladder sludge in four (4%) patients. Eighty-one patients had a normal gallbladder ultrasound. After bariatric surgery, these patients were followed prospectively with periodic gallbladder ultrasound examinations. At 6 months, gallstones had developed in 36% and gallbladder sludge in 13% of patients. These percentages remained relatively constant at 12 and 18 months. Body weight declined rapidly after surgery from a mean of 132.3 kg to 95.5, 87.0, and 84.0 kg at 6, 12, and 18 months, respectively. Gallstones developed significantly more often in the white race, and in women. No significant differences in age, body weight, percent ideal body weight, percent weight loss, or percent of excess body weight lost existed between patients who developed gallstones or sludge and those who did not. Patients who developed gallbladder sludge had less cholesterol and lower cholesterol saturation (1.25 +/- 0.42) in their gallbladder bile than persons who developed gallstones (2.00 +/- 0.79). Forty percent (13/32) of patients who developed gallstones became symptomatic; nine (28%) underwent elective cholecystectomy. An attempt to prevent gallstone formation during rapid weight loss appears warranted.

Adult↗
PubMed1991

Ibuprofen prevents deterioration in static transpulmonary compliance and transalveolar protein flux in septic porcine acute lung injury.

UNLABELLED: The effects of intravenous ibuprofen on measurements of pulmonary function and alveolar capillary membrane permeability to protein in sepsis-induced porcine acute lung injury (ALI) were studied. Young swine (15-25 kg) were anesthetized, cannulated, and ventilated (5 cm H2O PEEP, 0.5 FIO2, and 15 cc/kg tidal volume). Three groups were studied: septic animals (Ps, n = 10) received Pseudomonas aeruginosa for 1 hr IV, controls (C, n = 9) received 0.9% NaCl, and ibuprofen-treated septic animals (Ps + Ibu, n = 7) received ibuprofen 12.5 mg/kg at 0 and 120 min post Ps. Systemic (SAP) and pulmonary (PAP) arterial pressures, PaO2, cardiac index (CI), static lung compliance (CL), EVLW (thermal cardiogreen), and peripheral white blood cell counts (WBC) were measured. Bronchoalveolar lavage (BAL) was performed for protein and % neutrophil (%PMN) content. RESULTS: Ps produced significant (p less than 0.05) decreases in CL, PaO2, SAP, CI, and peripheral WBC and increases in PAP, EVLW, BAL protein, and %PMN's vs. controls. Ibu prevented the early increase in PAP and attenuated the late increase in PAP and EVLW. Ibu also maintained PaO2, CL, BAL protein, and %PMN's in BAL at control levels, but exhibited no significant effect on peripheral leukopenia. These data strongly suggest that ibuprofen administered before and at 120 min after onset of Pseudomonas infusion improves lung compliance and affects neutrophil function sufficiently to significantly ameliorate many of the physiologic derangements in acute sepsis.

Acute Disease↗
PubMed1990

Human gallbladder mucosal function. Effect of concentration and acidification of bile on cholesterol and calcium solubility.

The most recognized function of the human gallbladder is to store bile. However, this organ is not a static reservoir. It actively modifies bile by two processes: concentration and acidification. This study was designed to simultaneously evaluate the relationship between these two physiological processes in the normal human gallbladder and to define their effects on biliary cholesterol and calcium solubility. Bile was sampled directly from the gallbladder of 78 morbidly obese patients undergoing elective gastric bypass procedures. All had negative results of intra-operative ultrasound examinations for sludge and gallstones, normal liver function tests, and no history of hepatobiliary disease. Bile salt concentrations, an indirect index of concentration by the gallbladder, ranged from 15.1-272.8 mmol/L. As [bile salt] increased, [Na+], [K+], free [Ca2+], [cholesterol], [phospholipid], and [total lipid] increased linearly; [Cl-1] decreased linearly. Molar percent cholesterol decreased from 17.2% in dilute bile to 10.1% in fully concentrated bile, suggesting that cholesterol was absorbed by the gallbladder. As bile was concentrated, cholesterol saturation index decreased curvilinearly from a maximum of 3.7 in dilute bile to 1.0-1.5 in concentrated bile. Concentration of gallbladder bile was accompanied by progressive acidification. Bile pH decreased linearly with increasing [bile salt]; [CO3(2-)] decreased curvilinearly. Despite increasing [Ca2+], CaCO3 saturation index decreased curvilinearly with increasing [bile salt] from a maximum of 3.62 in dilute bile to a minimum of 0.12 in concentrated and acidified bile. CaCO3 saturation index also decreased exponentially with decreasing pH. This study concludes that concentration of bile enhances cholesterol solubility while acidification enhances calcium salt solubility. By increasing the solubilities of these two species, gallbladder mucosal function may play a key role in preventing gallstone formation.

Analysis of Variance↗
PubMed1990

Ibuprofen attenuates hypochlorous acid production from neutrophils in porcine acute lung injury.

UNLABELLED: Hypochlorous acid (HOCl), a neutrophil-generated oxidant, has been implicated in tissue destruction in sepsis-induced acute lung injury (ALI). Ibuprofen, a cyclooxygenase inhibitor, successfully attenuates many of the physiological derangements in ALI. The aim of this study was to examine the role of PMN hypochlorous acid in sepsis-induced ALI and evaluate the effect of ibuprofen therapy. Neutrophils from three groups of young (15-25 kg), anesthetized swine were studied: controls (C, n = 7) received 0.9% NaCl, septic animals (Ps, n = 8) received live Pseudomonas aeruginosa (5 x 10(8) CFU/ml at 0.3 ml/20 kg/min) for 60 min, and ibuprofen-treated animals (Ps + I, n = 6) received Ps plus ibuprofen 12.5 mg/kg administered at 0 and 120 min. Neutrophils were isolated from peripheral blood at 0, 60, and 300 min and the rate and total production of HOCl were assessed on the basis of the ability of the amino acid taurine to trap HOCl. RESULTS: Septic (Ps) PMNs produce 32% more HOCl, P less than 0.01, at 300 min than at baseline which was associated with a marked increase in both extravascular lung water (6.44 +/- 0.8 ml/kg, t = 0 vs 16.03 +/- 2.6 ml/kg, t = 300, P less than 0.01) and bronchoalveolar protein content (115 +/- 13 micrograms/ml, t = 0 vs 633 +/- 104 micrograms/ml, t = 300, P less than 0.01). Ibuprofen significantly attenuated (P less than 0.05) HOCl production when compared to Ps, in conjunction with significantly (P less than 0.05) reduced levels of extravascular lung water and bronchoalveolar lavage protein.

Animals↗