Systemic infusion of exogenous ghrelin in male broiler chickens (Gallus gallus domesticus). The effect of pulse frequency, doses, and ghrelin forms on feed intake, average daily gain, corticosterone, and growth hormone concentrations.

There is limited information on the effect of exogenous ghrelin infusion on feed intake (FI) in chickens. Therefore, male broilers were used in 3 factorial experiments to determine the relationships between doses (0, 1, or 4 nM; Dose), frequency (once every two h; 2 h), once every 4th h (4 h) or continuous infusion, and ghrelin forms including acylated-ghrelin (AG) and desacylated-ghrelin (DAG) on FI, ADG, and concentrations of corticosterone and Growth Hormone (GH). Treatments were delivered via a jugular cannula, using programmable pumps for 11 consecutive days. FI and ADG were recorded, and plasma was collected. Data were analyzed using a factorial design. In Experiment 1 the effect of AG pulse frequency and doses were evaluated. There was a linear decrease in FI (P = 0.002) and a linear increase in corticosterone (P = 0.033) and GH (P = 0.011) concentrations when AG was infused. However, ADG decreased with doses (P = 0.011) only when AG was given at 2 h. In Experiment 2 the effect of ghrelin forms and doses given at 2 h was evaluated. There was a linear decrease in FI when AG was infused and a linear increase in FI when DAG was infused (P < 0.05). Birds infused with DAG gained more weight than those infused with AG. There was a linear increase in corticosterone and GH concentrations only when AG was infused (P < 0.01). In Experiment 3 the effect of continuous infusion of 2 doses (0 and 1 nM) of AG and DAG were evaluated. There was a linear decrease in FI and ADG when AG (P < 0.001) was infused and a linear increase in FI and ADG when DAG was infused (P < 0.05). There was an increase in corticosterone concentrations only when AG was infused (P = 0.022). However, GH concentrations were not affected by treatments. We concluded that AG and DAG pulse frequency and doses had a differential effect on FI, ADG, corticosterone, and GH concentrations in broiler chickens.

Capromorelin, a ghrelin receptor agonist, increases feed intake and body weight gain in broiler chickens (Gallus gallus domesticus).

Ghrelin is a hormone that induces orexigenic effects in mammals. However, in avian species, there is scant and conflictive results on the effect of ghrelin on feed intake (FI). Therefore, we evaluated the effect of a ghrelin receptor agonist (capromorelin) on FI, ADG, water intake (WI), animal behavior and concentrations of ghrelin, glucose, growth hormone (GH) and insulin in broiler chickens. One-day-old male broilers were reared as recommended by the industry. At 4 wk of age (experimental day 0; D0), birds were blocked by weight and randomly assigned to 3 treatments in 2 identical trials. Control birds received a vehicle control solution containing 0 mg/kgBW/d of capromorelin. Birds in treatments 2 and 3 received capromorelin at target doses of 6 or 12 mg/kgBW/d of capromorelin (n = 27). FI and WI were measured 3 times a day at 0700 h (Period 1; P1), 1200 h (P2) and 1700 h (P3), while BW was recorded daily. Blood samples were collected on D-1 and D5. Bird behavior (pecking, sitting and standing) was evaluated for 9 h on D2. Data were analyzed using a randomized complete block design with repeated measures over time. Orthogonal polynomial contrasts were used to determine linear and quadratic effects of increasing levels of capromorelin. Polynomial contrasts showed that capromorelin doses linearly increased FI (P = 0.002) and ADG (P = 0.019). There were no treatment, day or treatment x d interactions on glucose, ghrelin and GH concentrations. However, there was a treatment x d interaction (P = 0.041) on insulin concentrations. Concentrations of insulin were higher on D5 for the 0 and 12 mg/kgBW/d treatments as compared with D-1. Polynomial contrasts showed that capromorelin doses linearly increased number of pecks/h (P = 0.018). Per hour FI and WI was higher during P1 (i.e., 0700-1200) as compared to P2 and P3 (P < 0.001). Our observations suggest that capromorelin linearly increases feed intake; thus, the same effect of that reported in mammalian species.

Effect of short- and long-term feed restriction on ghrelin concentrations in turkeys.

One-day-old broad-breasted white turkeys (Meleagris gallopavo) were reared as recommended by industry standards. In Experiment 1, starting at 5 wk of age (WOA), birds were placed in individual cages with free access to feed and water. Blood samples were taken after 18 h of fasting (FASTING) and at 90 ± 5 min after feeding (1.5 h after feeding). In Experiment 2, birds were weighed, randomly assigned to 2 treatments, and placed in individual cages. In treatment 1 (n = 10), birds were fed ad libitum (FF), while birds in treatment 2 (n = 11) were placed on a restricted diet to allow for an average daily gain of 10.0 g per d from 4 to 11 WOA (RES). In Experiment 1, concentrations of ghrelin (P = 0.012) and glucose (P < 0.001) were increased 1.5 h after feeding compared with concentration during FASTING, whereas concentrations of adrenocorticotropic hormone (ACTH) (P < 0.001) and corticosterone (P = 0.002) were decreased 1.5 h after feeding. Concentration of insulin, free fatty acids, and ketone bodies followed a normal physiological response to fasting and feeding. Similarly, in Experiment 2, concentrations of ghrelin (P < 0.001) and glucose (P = 0.038) were increased in FF birds, whereas concentrations of corticosterone were decreased (P = 0.002) in FF birds. It could be concluded that in turkeys, preprandial (18 h of fasting) and long-term feed restriction is associated with decreased concentration of ghrelin-thus, the opposite effect of that reported in chickens and mammalian species.

Does pure robotic partial nephrectomy provide similar perioperative outcomes when compared to the combined laparoscopic-robotic approach?

Laparoscopic and robotic partial nephrectomy have become the preferred option for surgical management of incidentally discovered small renal tumors. Currently there is no consensus on which aspects of the procedure should be performed laparoscopically versus robotically. We believe that combining a laparoscopic exposure and hilar dissection followed by tumor extirpation and renorrhaphy with robotic assistance provides improved perioperative outcomes compared to a pure robotic approach alone. We performed a comparison of perioperative outcomes between combined laparoscopic-robotic partial nephrectomy-or hybrid procedure-and pure robotic partial nephrectomy (RPN). A multi-center retrospective analysis of patients undergoing RPN and hybrid PN using the da Vinci S system(®) was performed. Patient data were reviewed for demographic and perioperative variables. Statistical analysis was performed using the Welch t test and linear regression, and nonparametric tests with similar significance results. Thirty-one patients underwent RPN while 77 patients underwent hybrid PN between 2007 and 2011. Preoperative variables were comparable in both groups with the exception of lesion size and nephrometry score which were significantly higher in patients undergoing hybrid PN. Length of surgery, estimated blood loss and morphine used were significantly less in the hybrid group, while warm ischemia time was significantly longer. The difference in WIT was accounted for in this data by adjusting for nephrometry score. In our multi-center series, the hybrid approach was associated with a shorter operative time, reduced blood loss and lower narcotic usage. We believe this approach is a valid alternative to RPN.

Combinational Effects of Prebiotics and Soybean against Azoxymethane-Induced Colon Cancer In Vivo.

Prebiotic fructans are nondigestible carbohydrates with numerous health benefits. Soybean is a rich source of phytonutrients such as isoflavones. The objective of this study was to evaluate the chemopreventive effects of prebiotics (Synergy1) and soybean meal (SM) at 5% and 10% levels alone and in combination on azoxymethane- (AOM-) induced colon carcinogenesis. After one wk of acclimatization, Fisher 344 male rats (N = 90) were randomly assigned to 9 groups (n = 10). Control rats (C) were fed AIN-93G/M. Two s/c injections of AOM were administered to rats at 7 and 8 wk of age at 16 mg/kg body weight. Rats were killed by CO(2) asphyxiation at 45 wk. Tumor incidence (%) in treatment groups ranged from 40 to 75 compared to 100 in C. Results indicate that feeding prebiotics and soybean in combination significantly reduced incidence of AOM-induced colon tumors with implications for food industry in the food-product development.

Chemopreventive potential of synergy1 and soybean in reducing azoxymethane-induced aberrant crypt foci in fisher 344 male rats.

Synergy1, a prebiotic composed of Inulin and Oligofructose (1 : 1). Soybean meal is a natural source of isoflavones. The objective was to investigate the effects of feeding Synergy1 and SM on the incidence of azoxymethane- (AOM-) induced aberrant crypt foci (ACF) in Fisher 344 male rats. Rats (54) were randomly assigned to 9 groups (n = 6). Control group (C) was fed AIN-93G and treatment groups Syn1 and SM at 5% and 10% singly and in combinations. Rats were injected with two s/c injections of AOM at 7 and 8 weeks of age at 16 mg/kg body weight and killed at 17 weeks by CO(2) asphyxiation. Colonic ACF enumeration and hepatic enzyme activities were measured. Reductions (%) in total ACF among treatment groups fed combinations were higher (67-77) compared to groups fed singly (52-64). Synergistic mechanisms among phytochemicals may be responsible suggesting protective role in colon carcinogenesis with implications in food product development.

Massive chondroid hamartoma of the lung clinically masquerading as bronchogenic carcinoma.

Chondroid hamartomas of the lung are uncommon lesions which are generally small sized and asymptomatic. Herein we describe a case of a large-sized pulmonary chondroid hamartoma which clinically mimicked bronchogenic carcinoma. A large hilar growth was detected in the left lung on radiological studies. Left upper lobectomy was done. The growth was well defined with a lobulated bluish cut surface. Histopathology disclosed lobules of mature cartilage rimmed by long slit-like epithelial channels admixed with mature adipose tissue.

Selected fruits reduce azoxymethane (AOM)-induced aberrant crypt foci (ACF) in Fisher 344 male rats.

Phytochemicals contribute to the vibrant colors of fruits and it is suggested that the darker the fruit the higher the antioxidative or anticarcinogenic properties. In this study we investigated the possible effects of blueberries (BLU), blackberries (BLK), plums (PLM), mangoes (MAN), pomegranate juice (POJ), watermelon juice (WMJ) and cranberry juice (CBJ) on azoxymethane (AOM)-induced aberrant crypt foci (ACF) in Fisher 344 male rats. Forty-eight male Fisher 344 rats were randomly assigned to eight groups (n=6). The groups were fed AIN-93G as a control (C) diet, the rats fed fruits received AIN-93G+5% fruits and the groups that were given fruits juices received 20% fruit juice instead of water. The rats received subcutaneous injections of AOM at 16 mg/kg body weight at seventh and eighth weeks of age. At 17th week of age, the rats were killed by CO(2) asphyxiation. Total ACF numbers (mean+/-SEM) in the rats fed CON, BLU, BLK, PLM, MNG, POJ, WMJ and CBJ were 171.67+/-5.6, 11.33+/-2.85, 24.0+/-0.58, 33.67+/-0.89, 28.67+/-1.33, 15.67+/-1.86, 24.33+/-3.92 and 39.0+/-15.31. Total glutathione-S-transferase (GST) activity (mICROmol/mg) in the liver of the rats fed fruits (except BLK) and fruit juices were significantly (p<0.05) higher in the rats fed fruits and fruit juices compared with the control. Our findings suggest that among the fruits and fruit juices, BLU and POJ contributed to significant (P<0.05) reductions in the formation of AOM-induced ACF.

Flax seed oil and flax seed meal reduce the formation of aberrant crypt foci (ACF) in azoxymethane-induced colon cancer in Fisher 344 male rats.

Flax seed oil and flax seed meal are good sources of omega-3 fatty acids. The objective of this study was to explicate the effects of feeding flax seed oil and flax seed meal on AOM-induced aberrant crypt foci (ACF) in Fisher 344 male rats. Following an acclimatization period, rats were divided into six groups and fed AIN 93G diet Control (C), C+7 and 14% soybean oil (SBO), C+7 and 14% flax seed oil (FSO) and C+10 and 20% flax seed meal (FSM). All rats received 16 mg/kg body weight of AOM at 7 and 8 weeks of age. The rats were euthanized with CO2 at 17 weeks of age. FSM and FSO reduced the incidence of ACF which are putative precursor lesions in the development of colon cancer in the distal colon by 88% and 77%, in the proximal colon by 86% and 87% with a total reduction of 87.5% and 84%, respectively. Glutathione-S-transferase (GST) activities were significantly (P<0.05) higher in rats fed C+7 and 14% FSO and C+10 and 20% FSM, as compared to rats fed C+SBO diets. Results of this study showed that FSO and FSM reduced the incidence of AOM-induced ACF formation and may therefore be effective chemopreventive agents.

Red palm oil suppresses the formation of azoxymethane (AOM) induced aberrant crypt foci (ACF) in Fisher 344 male rats.

Red palm oil (RPO) contains significant levels of carotenoids and Vitamin E. In this experiment we compared the inhibitory effects of RPO (7% and 14% levels) and soybean oil (7% and 14%) on azoxymethane (AOM) induced aberrant crypt foci (ACF). Thirty-two male Fisher 344 rats were randomly assigned to four groups. Two groups received AIN-93 G control (C) diet containing 7% and 14% soybean oil (SBO), respectively. Groups 3 and 4 received a treatment diet consisting of 7% and 14% RPO, respectively. The rats received subcutaneous injections of AOM at 16 mg/kg body weight at 7 and 8 weeks of age. At 17 weeks of age rats were killed by CO(2) asphyxiation. Numbers of ACF (mean+/-SE) in the proximal and distal colon were: 39.9 +/- 0.9, 53.8 +/- 2.8, 26.0 +/- 3.0, 27.5 +/- 1.5 and 118.2 +/- 1.7, 125.6 +/- 3.2, 41 +/- 7, 52.3 +/- 1.8 in rats fed 7% SBO, 14% SBO, 7% RPO and 14% RPO, respectively. The results of this study showed that RPO reduced the incidence of AOM induced ACF and may therefore have a beneficial effect in reducing the incidence of colon cancer.

Dietary inulin suppresses azoxymethane-induced preneoplastic aberrant crypt foci in mature Fisher 344 rats.

Preneoplastic aberrant crypt foci (ACF) are generally accepted as reliable markers for colon carcinogenesis in animal models. Rat model ACF studies, however, use younger rats, and there are no published reports on the suitability of adult rats for ACF studies. In this study, inulin, a known suppressor of azoxymethane (AOM)-induced ACF, was tested for its ability to suppress ACF formation in mature rats. After a 2-wk acclimation period, 12-mo-old Fisher 344 retired male breeders received two subcutaneous injections of AOM dissolved in saline at weekly intervals. In experiment 1, six groups received 0, 4, 8, 10, 12 and 16 mg AOM/kg body at each injection and were fed AIN-93M diet. In experiment 2, four groups of rats were fed 10 mg AOM/kg body at each injection based on the results of experiment 1, and were fed 0, 2.5, 5 and 10 g long-chain inulin diets/100 g. All the rats were killed after 11-wk feeding periods. In experiment 1, there was a significant (P < 0.05) AOM dose response on ACF formation. Rats fed >10 mg of AOM had greater (P < 0.05) mortality. In experiment 2, there was a significant increase in cecal weight and a decrease in cecal pH from 7.17 in the control group to 6.87, 6.61 and 5.76 in the groups fed inulin at 2.5, 5.0 and 10 g/100 g, respectively. Long-chain inulin dose-dependently reduced ACF incidence in the colon (P < 0.01). Compared with rats fed the control diet, the percentage reductions of ACF in rats fed 2.5, 5.0 and 10 g inulin diets/100 g were 25, 51, and 65, respectively. The results of this study indicate that mature rats can be used as models in ACF studies, and dietary long-chain inulin dose-dependently suppresses AOM-induced ACF formation in Fisher 344 mature male rats.

Dietary inulin suppresses azoxymethane-induced aberrant crypt foci and colon tumors at the promotion stage in young Fisher 344 rats.

This study was designed to determine the effect of 10% dietary long-chain inulin on the azoxymethane (AOM)-induced colonic preneoplastic aberrant crypt foci (ACF) and small intestinal and colon tumors at the initiation (I), promotion (P) and I + P stages (20 rats per treatment) in Fisher 344 male weanling rats. After an acclimatization period of 1 wk, groups of Fisher 344 male weanling rats were assigned to consume AIN 93G diet (control) or AIN 93G diet containing 10% inulin. All the rats received 16 mg/kg body AOM dissolved in saline subcutaneously at 7 wk of age followed by a second injection at 8 wk of age. An additional group of five rats received only saline and consumed the control diet. The rats received the assigned diets until asphyxiation by CO(2) at 16 wk of age for the ACF experiment and 45 wk for the end-point tumor experiment. Feed intake, weight gain, diarrheal index, cecal weight, cecal pH, ACF and tumors in the colon were determined. Rats fed inulin had diarrhea after 2 wk of feeding and recovered by approximately 4 wk. Cecal weight was greater in rats fed inulin and cecal pH was lower. The inulin group had more than 66% fewer aberrant crypts and 60% fewer ACF compared with the control group. Tumor incidences in the small intestine and colon of rats in the control, I, P and I + P groups were: 78, 31, 0 and 11% and 90, 73, 69 and 50%, respectively. The corresponding values for the distal portion of the colon were 87, 63, 45 and 33%, respectively. Colon tumors per tumor-bearing rat were 4.2, 3.09, 1.36 and 1.2 for the control, I, P and I + P groups, respectively. All groups differed, P < 0.05. The results of this study indicate that dietary long-chain inulin suppresses AOM-induced ACF formation, an early preneoplastic marker of colon tumorigenesis in rats, and colon tumors, particularly at the promotion stage.

Targeted disruption of the leukotriene B(4) receptor in mice reveals its role in inflammation and platelet-activating factor-induced anaphylaxis.

Leukotrienes are derived from arachidonic acid and serve as mediators of inflammation and immediate hypersensitivity. Leukotriene B(4) (LTB(4)) and leukotriene C(4) (LTC(4)) act through G protein-coupled receptors LTB(4) receptor (BLTR) and Cys-LTR, respectively. To investigate the physiological role of BLTR, we produced mice with a targeted disruption of the BLTR gene. Mice deficient for BLTR (BLTR(-/-)) developed normally and had no apparent hematopoietic abnormalities. Peritoneal neutrophils from BLTR(-/-) mice displayed normal responses to the inflammatory mediators C5a and platelet-activating factor (PAF) but did not respond to LTB(4) for calcium mobilization or chemotaxis. Additionally, LTB(4) elicited peritoneal neutrophil influx in control but not in BLTR(-/-) mice. Thus, BLTR is the sole receptor for LTB(4)-induced inflammation in mice. Neutrophil influx in a peritonitis model and acute ear inflammation in response to arachidonic acid was significantly reduced in BLTR(-/-) mice. In mice, intravenous administration of PAF induces immediate lethal anaphylaxis. Surprisingly, female BLTR(-/-) mice displayed selective survival (6 of 9; P = 0.002) relative to male (1 of 11) mice of PAF-induced anaphylaxis. These results demonstrate the role of BLTR in leukotriene-mediated acute inflammation and an unexpected sex-related involvement in PAF-induced anaphylaxis.

CD14-dependent lipopolysaccharide-induced beta-defensin-2 expression in human tracheobronchial epithelium.

The induction of host antimicrobial molecules following binding of pathogen components to pattern recognition receptors such as CD14 and the Toll-like receptors (TLRs) is a key feature of innate immunity. The human airway epithelium is an important environmental interface, but LPS recognition pathways have not been determined. We hypothesized that LPS would trigger beta-defensin (hBD2) mRNA in human tracheobronchial epithelial (hTBE) cells through a CD14-dependent mechanism, ultimately activating NF-kappa B. An average 3-fold increase in hBD2 mRNA occurs 24 h after LPS challenge of hTBE cells. For the first time, we demonstrate the presence of CD14 mRNA and cell surface protein in hTBE cells and show that CD14 neutralization abolishes LPS induction of hBD2 mRNA. Furthermore, we demonstrate TLR mRNA in hTBE cells and NF-kappa B activation following LPS. Thus, LPS induction of hBD2 in hTBE cells requires CD14, which may complex with a TLR to ultimately activate NF-kappa B.

Neonatal audit in the United Arab Emirates: a country with a rapidly developing economy.

We aimed to determine whether birth-weight-specific mortality rates and causes of neonatal death could identify interventions needed to reduce neonatal mortality rates. Data were collected from three hospitals responsible for 99% of births in Al-Ain Medical District. There were 8083 live births weighing > or = 500 g, of which 54 (0.67%) died. The mortality rate among very low-birth-weight infants was higher in this district than from centres with more advanced neonatal technology and resources. Problems of preterm births, lethal malformations and asphyxia accounted for 95% of deaths and half of the malformations were autosomal recessive syndromes. Improved management of lower-birth-weight infants, asphyxia and genetic counselling could lead to a further decline in neonatal mortality rates.

Function and regulation of chemoattractant receptors.

Phagocyte migration and activation at sites of inflammation is mediated through chemoattractant receptors that are coupled to G-proteins. Early studies from our laboratory demonstrated G-protein-mediated phospholipase C activation by chemoattractants. Recently, this laboratory developed cellular and animal models to allow biochemical, cell biological and molecular genetic approaches to be used in determining the mechanisms of chemoattractant receptor function, regulation, and cross regulation. These studies provided evidence that chemoattractant receptors activate distinct pathways for chemotaxis and exocytosis and cross-regulate each other's function at multiple levels. A major site of regulation is through phosphorylation of receptors by G-protein-coupled receptor kinases and by protein kinase C. In addition, the activation of phospholipase C by chemoattractants is also regulated at additional sites distal to receptor phosphorylation. These may include modulation of G-protein activation by regulators of G-protein signaling (RGS) and modification of phospholipase C. Phosphorylation of phospholipase Cbeta3 by both protein kinase A and protein kinase C has been demonstrated. The function and regulation of chemoattractant receptors are also being examined in mouse models. In these studies, mice deficient in leukotriene B4 receptors have been generated by targeted gene disruption. These mice displayed reduced neutrophil accumulation in certain inflammation models and sex-related differences in platelet-activating-factor induced anaphylaxis.

Purification and characterization of a type II phosphatidylinositol 4-kinase from rat spleen and comparison with a PtdIns 4-kinase from lymphocytes.

A PtdIns 4-kinase from rat spleen particulate fraction was purified to homogeneity and its molecular properties were compared with a PtdIns 4-kinase from splenic lymphocytes. The enzyme activity was solubilized from spleen particulate fraction with Triton X-100 and chromatographed sequentially on phosphocellulose, DEAE-sephacel, heparin acrylamide and hydroxyapatite columns. The purified enzyme preparation showed a 55 kDa band on SDS-PAGE with silver staining. Renaturation of the enzyme activity from SDS-PAGE showed that it comigrated with the 55 kDa protein. Characterization of the enzyme showed that it was a type II PtdIns 4-kinase. Polyclonal antibodies raised against PtdIns 4-kinase inhibited the enzyme activity in in vitro assays. Analysis of adult rat tissue particulate fractions on immunoblots showed restricted immunoreactivity among PtdIns 4-kinases. However, the immunoreactivity is conserved in lymphoid tissues from mouse to human, suggesting that lymphoid tissue has a distinct PtdIns 4-kinase. Activation of rat splenocytes with Con A showed two fold increase in PtdIns 4-kinase activity. Comparison of PtdIns 4-kinases from spleen and splenic lymphocytes showed identical chromatographic behaviour, molecular mass, immunoreactivity, K(m) values for PtdIns and inhibition by adenosine.

Transabdominal gastroesophageal devascularization without esophageal transection for emergency treatment of variceal hemorrhage.

BACKGROUND: The Suguira procedure is an effective non-shunting operation to treat life-threatening hemorrhage from esophageal or gastric varices. The goal of esophageal transection is interruption of submucosal varices, but this leads to high morbidity and mortality rates from esophageal fistulization. AIM: To evaluate a variant of this procedure in which the esophagus is not transected, but the varices are underrun from outside the lumen. METHODS: During the last four and a half years, we performed this modified gastroesophageal devascularization with or without splenectomy in 18 patients as emergency treatment of bleeding esophageal and gastric varices. The data were analyzed retrospectively. RESULTS: Bleeding was controlled in all patients. Three patients with Child's class C disease undergoing emergency surgery died during the early postoperative period. Rebleeding rate was 17% (3 patients). The overall survival was 72.2% (13 of 18). No patient had encephalopathy over a mean follow up of 30 months. CONCLUSION: Gastroesophageal devascularization with variceal under-running without esophageal transection is an effective and safe alternative to shunt surgery in the emergency situation.

Effects of ion composition and tonicity on human neutrophil antibacterial activity.

Infants with cystic fibrosis (CF) often are infected with Staphylococcus aureus (S. aur.), which is followed by colonization with Pseudomonas aeruginosa (P. aerug.). In spite of an excessive, neutrophil-dominated inflammatory response in the respiratory tract, patients with CF often succumb to pulmonary infections with P. aerug. Because peripheral blood neutrophils of these patients have normal functions, we examined whether hypothesized alterations of the airway surface liquids (ASL) in these patients significantly impair neutrophil bactericidal activity in the microenvironment of the CF lung. The ionic composition of CF ASL is still not entirely defined and has been speculated to be abnormally high or abnormally low in Na+ and Cl- concentrations; estimates of osmolarities have ranged from 200 (hypo-osmolar) to 285 (iso-osmolar) to > 300 meq/L (hyper-osmolar). Our data indicate that bacterial killing activity of human peripheral blood neutrophils against P. aerug. or S. aur. is not decreased in buffers in which NaCl was replaced with equimolar concentrations of choline Cl, KCl, or N-methyl-D-glucamine chloride to maintain isotonicity. Amiloride or benzamil, known modulators of Na+ transport in neutrophils, did not interfere with this neutrophil function. Deviations from isotonicity of +/- 50% also failed to diminish bactericidal activity of neutrophils significantly. In contrast, superoxide production and enzyme secretion in response to the chemotactic peptide N-formylmethionylleucylphenylalanine appeared to be sensitive to the ionic milieu of the assay buffers. Our results suggest that the postulated alterations in the ionic composition of ASL in CF lungs are insufficient to explain why neutrophils fail to clear infections with P. aerug. in these patients.