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The advent of total-body PET/CT presents an opportunity for significant advancements in imaging of neuroblastoma with [18F]meta-fluorobenzylguanidine ([18F]mFBG). Small voxel imaging has proven to have better lesion detectability but need enough radioactivity counts. This study aims to balance shortened acquisition times and small voxel reconstruction to keep sufficient image quality and diagnostic confidence on [18F]mFBG total-body PET for neuroblastoma. We retrospectively enrolled 33 pediatric patients with neuroblastoma who underwent 37 [18F]mFBG total-body uEXPLORER PET/CT scans of 10-min duration. PET images were reconstructed with varying acquisition times (0.5-10 min) and three matrix sizes (192 × 192, 512 × 512 and 1024 × 1024). The subjective (scored on a 5-point scale) and objective image quality (signal-to-noise ratio, SNR) of all the sets of reconstructed images were analyzed by nuclear medicine physicians. For indeterminate lesions identified in the group of 192 × 192 matrix with the 10-min scan (G192-10), diagnostic confidence was further evaluated in images reconstructed with the 512 × 512 and 1024 × 1024 matrices (G512 and G1024). Of the 33 patients with 37 [18F]mFBG PET/CT scans, 17 patients with 20 scans had positive [18F]mFBG PET/CT findings. Sufficient subjective image quality was achieved with at least 2-min acquisition of 192 × 192 matrix and 4-min acquisition of 512 × 512 matrix (with all scores ≥ 3). SNR increased with longer acquisition times for the same voxel size, while decreased as voxel size shrunk. Although the Curie and SIOPEN scores remained consistent across G192, G512, and G1024-10 groups, the G512 groups with at least 2-min acquisition and G1024-10 showed significantly higher confidence scores for characterizing indeterminate lesions on the G192-10 images, with almost all indeterminate lesions being rated as very confident. A matrix of 512 × 512 with a minimum of 4-min acquisition on [18F]mFBG total-body PET/CT is recommended for sufficient image quality and improved diagnostic confidence, particularly in detecting indeterminate lesions.

Increasing number of patients are undergoing surgical treatment for adult spinal deformity (ASD). The main indications are pain, disability and loss of function. Multiple patient- reported health related quality of life (HRQOL) measures are utilized to assess functional status and disability before and after the surgery. Some components of these questionnaires may be more pertinent in the elderly population. Primary aim was to assess key functional outcomes were most relevant to elderly patients undergoing multilevel fusion surgery for ASD. Secondary aim was to assess if these functional improvements were maintained over the follow up period. Post hoc analysis of prospectively collected data from multicenter observational study, where primary outcome was the absolute changes in the SRS-22r total and subtotal scores between baseline and 2-years FU. Two Hundred nineteen patients. Self-reported and functional measures were included. Function was assessed using the Scoliosis Research Society 22r (SRS-22r) function domain, and the personal care, walking, sitting and standing sections from the Oswestry disability index (ODI) and EuroQol- 5 Dimension (EQ-5D-3L scores). Patients ≥60 years of age from 12 international centres undergoing spinal fusion of at least 5 levels were included. Follow up visits were performed at 10 weeks, 12 months, 24 months and 60 months. A total of 219 patients (80.4% females) were included with a mean age of 67.5 years. The mean SRS-22r function scores preoperative were 2.70 (CI: 2.60-2.80), which improved to 3.46 (CI: 3.36-3.56) by 2 years postsurgery and were maintained at 5 years (3.39, CI: 3.27-3.51). 44.9% patients were either bedbound or had primarily no activity before the surgery which reduced to 18.3 % at 2 years and 17.4% at 5 years follow up. Similarly, the percentage of patients that could stand >30 minutes improved from 24.5% to 68.6% at 2 years and 59.4% at 5 years. 26% of the patients could walk for a mile or more before surgery which improved to 63.1 % at 2 years and maintained in 58.7% patients at 5 years. 43.1 % had unlimited sitting preoperatively, that improved to 65.3% at 2 years and 64.7% at 5 years. Normal social life was seen in 19.2% of patients at baseline compared to 57.5% at 2 years and 52.7% at 5 years. Elderly patients undergoing multilevel spinal fusions for ASD experienced significant functional improvements, which were maintained at 5 years postoperatively. This practical information can be utilized during patient counselling preoperatively when considering functional outcomes after major ASD surgery in patients over 60 years of age.

To evaluate the concentration of natural radionuclides and to carry out geophysical interpretation of part of Igarra area, Southern Nigeria, an integrated geophysical approach was adopted involving radiometric, gravity, and magnetic methods. The RS-230 Super-Spec spectrometer, G-512 Lacoste and Romberg gravimeter, and the GSM-19v7.0 Overhauser instrument were used for the radiometric, gravity, and magnetic data acquisitions, respectively, along a specified traverse within the area. The datasets were processed using Oasis Montaj, Grav-Master, and Ms-Excel software. Gravity results show that the mean free air and Bouguer anomalies in the area are - 67.42 and - 84.22 mGal, while magnetic survey indicates that the mean corrected magnetic field intensity in this area is 32218.49 nT. Radiometric survey results show that the mean radioactivity concentrations of thorium ([Formula: see text], uranium ([Formula: see text]), and potassium ([Formula: see text]) are 31.81 Bq/kg, 26.48 Bq/kg, and 167.33 Bq/kg, respectively. Further analysis also revealed that the mean radioactivity equivalent of the area is 84.86 Bq/kg; absorbed dose rate is 72.74nGy/h, while the mean external hazard index is 0.30. A novel model equation for estimating absorbed dose rate from radioactivity equivalent was also obtained and validated. The gravity and magnetic survey results indicate the presence of low-density and high magnetic basement rocks underlying this area, while radiometric results reveal that radiations in this area did not exceed acceptable standards of 370 Bq/kg for radioactivity equivalent, 84 nGy/h for absorbed dose rate, and unity which corresponds to 370 Bq/kg for external hazard index as recommended by the United Nations Scientific Committee on the Effects of Atomic Radiation and the International Atomic Energy Agency.

Levofloxacin (LVX) and Moxifloxacin (MXF) are the cornerstones for treatment of multidrug-resistant tuberculosis (MDR-TB). China is one of the highest MDR- and fluoroquinolones (FQ)-resistant TB burdens countries. DNA gyrase encoded by gyr genes is the main target of FQ in Mycobacterium tuberculosis (MTB). The prevalence and molecular characterization of LVX- and MXF-resistant MTB strains from southern China were examined in this study. Drug susceptibility testing (DST) of 400 MTB clinical isolates was evaluated by proportion method on Löwenstein-Jensen (LJ) medium against ten drugs. The sequencing of entire gyrA and gyrB genes and multiplex PCR were performed to distinguish the prevalence of mutant types in Beijing and non-Beijing genotypes. Three hundred and twenty-one out of four hundred (80.25%) drug-resistant isolates (resistant > one drug) were categorized as 83/321 (25.80%) MDR, 174/321 (54.20%) pre-XDR and 64/321 (19.93%) XDR-MTB. Overall, 303/400 (75.75%) LVX- and 292/400 (73.00%) MXF-resistant (R) MTB strains were identified. Two hundred seventy-one out of three hundred and three (89.43%) resistant strains carried mutations in gyrA and 91/303 (30.03%) in gyrB. Interestingly, 18 novel mutations were detected in gyrA and gyrB genes. Mutations at (A90, D94) and (T500, G510, G512) frequently existed in QRDR(s) of gyrA and gyrB respectively in 286/400 (71.50%) LVXRMXFR strains. The novel mutations in- and out-side the QRDR of gyrA (L105R, A126E, M127K, D151T, V165A) and gyrB (D461H, N499S, G520A) increased the sensitivity and consistency of genotypic tests. Notably, 25 LVXRMXFR strains were found with unknown resistance mechanisms. Mutations in QRDR(s) were concomitantly associated with Beijing and non-Beijing genotypes. The prevalence of resistance and cross-resistance between LVX and MXF in MTB isolates from southern China was immensely higher than other countries. Our valuable findings provide the substantial implications to improve the reliability of genotypic diagnostic tests relying on potential resistance conferring mutations in entire gyr genes.

To compare receptors for cholecystokinin (CCK) in pancreas and gallbladder, we measured binding of 125I-Bolton-Hunter-labeled CCK-8 (125I-BH-CCK-8) to tissue sections from guinea pig gallbladder and pancreas under identical conditions. In both tissues, binding had similar time-, temperature-, and pH dependence, was reversible, saturable and inhibited only by CCK related peptides or CCK receptor antagonists. Autoradiography localized 125I-BH-CCK-8 binding to the smooth muscle layer in the gallbladder. Binding of 125I-BH-CCK-8 to gallbladder sections was inhibited by various agonists with the following potencies (IC50):CCK-8 (0.4 nM) greater than des(SO3)CCK-8 (0.07 microM) greater than gastrin-17-I (1.7 +/- 0.3 microM) and by various receptor antagonists with the following potencies: L364,718 (1.5 nM) greater than CR 1409 (0.19 microM) greater than asperlicin = CBZ-CCK-(27-32)-NH2 (1 microM) greater than Bt2cGMP (120 microM). Similar potencies were found for the agonists and antagonists for pancreas sections. Inhibition of binding of 125I-BH-CCK-8 by 11 different analogues of proglumide gave similar potencies for both pancreas and gallbladder. The potencies of agonists in stimulating and antagonists in inhibiting CCK-stimulated contraction or amylase release correlated closely with their abilities to inhibit 125I-BH-CCK-8 binding to gallbladder or pancreas sections or acini, respectively. The present results demonstrate and characterize a method that can be used to compare the CCK receptors in guinea pig gallbladder and pancreas under identical conditions. Moreover, this study demonstrates that gallbladder and pancreatic CCK receptors have similar affinities for the various agonists and antagonists tested and, therefore, provides no evidence that they represent different subtypes of CCK receptors that can be distinguished pharmacologically.

Esophageal shortening accompanies peristalsis in laboratory animals and is attributed to longitudinally oriented fibers in esophageal muscle layers. To evaluate this phenomenon in humans, esophageal shortening during suspended respiration in response to swallows was measured in five normal volunteers (median age, 23 yr). Metal mucosal clips were endoscopically placed at and 10 cm above the gastroesophageal junction, and their movement was recorded by videotaped fluoroscopy. All subjects demonstrated esophageal shortening with each swallow in a characteristic pattern with small interswallow variance. Early, minimal shortening of the proximal segment (6.0 +/- 2.4 mm) was followed by delayed, prominent distal segment shortening (18.9 +/- 9.3 mm) that principally accounted for overall change in total esophageal length (18.0 +/- 8.1 mm). The degree of esophageal shortening did not correlate with circular muscle contraction wave parameters that were obtained with intraluminal manometrics in a separate study (P greater than 0.2 for each correlation), and distal segment shortening uniformly preceded the onset of contraction waves in the same region. These findings indicate that patterned esophageal shortening with swallows occurs in humans, most prominently in the distal esophagus. The technique may be useful in determining the participation of axial esophageal movement in esophageal motility disorders.

Interactions of some dialkylaminoalkyl (DAL) and dialkylaminoacyl (DAC) derivatives of phenothiazine and dibenzazepine with muscarinic cholinergic receptors (MR) of rabbit striatum and heart and rat brain were investigated. DAC derivatives were more active at brain and heart MR in some cases. The most active preparation was G-512, DA-analogue of chlorpromazine. Some cardiotropic properties of antianginal preparation nonachlazine may be connected with its central antimuscarinic activity.

Significant pelvic ring fractures are usually secondary to high-energy trauma, and when associated with other life-threatening injuries and hemodynamic instability, result in high mortality rates ranging from 40 to 60%. The major cause of death during the first 24 h after pelvic trauma is attributed to acute blood loss, with later mortality secondary to multisystem organ failure. In a majority of patients, the source of pelvic bleeding is from disruption of the presacral venous plexus and bony fracture sites, while arterial injury is present in only 10-15%. The optimal management algorithm for hemodynamically unstable patients with pelvic fractures remains controversial. The principles of care center on resuscitation, external stabilization of the pelvis, and hemorrhage control with angiography and embolization (AE) and/or preperitoneal pelvic packing (PPP). AE is effective in controlling arterial bleeding and its role in the management of hemodynamically unstable patients with pelvic fractures is supported by the EAST guidelines. However, since most patients suffer from venous bleeding, PPP can be an alternate life saving technique to control hemorrhage, especially if AE is not immediately available.

New dialkylaminoacyl phenothiazine derivatives (DAC) were compared with their dialkylaminoalkyl analogues (neuroleptics chlorpromazine, trifluoperazine and fluphenazine) as well as with anti-arrhythmia drugs ethmozine and ethacizine for their receptor-blocking potencies. It was established that DAC are significantly less potent with dopamine alpha 1-adrenergic and H1-histamine receptors of calf and rabbit brain, which can explain the absence of neuroleptic effect of DAC drugs. DAC affinities to muscarinic and alpha-adrenergic receptors of both types are very similar to those of ethmozine and ethacizine. New DAC substance G-512 (chlorpromazine analogue) demonstrated high affinity to M1-muscarinic receptors of rabbit brain cortex (Ki = 4.2 nM) and to M2-muscarinic receptors of the rabbit heart (Ki = 48 nM).

Regulation of cholecystokinin (CCK) secretion was studied in conscious unrestrained rats by simultaneous duodenal perfusion with foodstuffs, intravenous infusion of hormones or neural agents, and arterial blood sampling for CCK bioassay. Duodenal infusion of casein resulted in elevation of plasma CCK from fasting level of 0.5 +/- 0.1 to 3.8 +/- 0.4 pM. Casein hydrolysate, calcium, and glucose did not elevate plasma CCK. Infusion of intact fat had a small, but nonsignificant, effect (1.4 +/- 0.4 pM), whereas infusion of oleate increased plasma CCK to 3.7 +/- 0.6 pM. Thus intact protein and fatty acids are the major dietary intestinal stimuli for CCK release in the rat. The CCK response to protein could be inhibited by somatostatin but not by peptide YY (0.2, 2, or 20 micrograms.kg-1.h-1); intravenous infusion of 1 or 10 micrograms.kg-1.h-1 somatostatin decreased casein-stimulated CCK levels to 1.5 +/- 0.2 and 0.9 +/- 0.3 pM, respectively. Stimulation of vagal discharge with 2-deoxy-D-glucose had no effect on basal or protein-stimulated plasma CCK levels; thus CCK release in the rat does not appear to be modulated by central vagal pathways. Gastrin-releasing peptide increased fasting plasma CCK levels to 1.6 +/- 0.1 pM. Administration of the cholinergic agonist bethanechol, while having no effect on fasting CCK level, inhibited protein-stimulated plasma CCK from 3.9 +/- 0.6 to 1.3 +/- 0.3 pM. Cholinergic blockade with atropine, in contrast, had no effect on basal or protein-stimulated plasma CCK. Thus CCK release is stimulated by dietary protein or fatty acid and by gastrin-releasing peptide and inhibited by somatostatin and bethanechol.

The objective of this study is to evaluate the role of Crooke's changes (CC) in normal the peri-tumoral anterior pituitary gland, in patients with Cushing's disease (CD) with a histopathological confirmed corticotroph adenoma, and determine if there is any difference in the recurrence and remission rates in CD patients after treatment with Gamma Knife Radiosurgery (GKRS). All patients treated with GKRS for CD from 2005 to 2016 at our institution were identified. Patients had a confirmed adrenocorticotropic (ACTH)-secreting adenoma, i.e. corticotroph adenoma, and normal pituitary gland included in the surgical specimen, and specimens were stained with hematoxylin and eosin and also immunostaining for cytokeratin and ACTH. Statistical analyses were performed in a total of 61 patients who met the inclusion criteria. Additionally, we analyzed 20 patients in each group, with and without CC, after they were matched in a propensity score fashion. Endocrine remission defined as, a normal 24 h urine free cortisol while off suppressive medication, occurred in 48 patients (78.7%), with 76.9% in those with CC and 81.8% in those without CC. There was no statistical significant difference between the two groups in regarding remission (p = 0.312) or recurrence (p = 0.659) in either the unmatched or matched cohorts. The presence or absence of CC in normal pituitary gland does not appear to confer a lower rate of remission or a higher rate of recurrence after GKRS. Patients with pituitary corticotroph adenomas that present with CC features may be well served by Stereotactic radiosurgery (SRS).

One prime feature of alcoholic liver disease (ALD) is iron accumulation in hepatic macrophages/Kupffer cells (KC) associated with enhanced NF-kappaB activation. Our recent work demonstrates a peroxynitrite-mediated transient rise in intracellular labile iron (ILI) as novel signaling for endotoxin-induced IKK and NF-kappaB activation in rodent KC. The present study investigated the mechanism of KC iron accumulation and its effects on ILI response in experimental ALD. We also tested ILI response in human blood monocytes. Chronic alcohol feeding in rats results in increased expression of transferrin (Tf) receptor-1 and hemochromatosis gene (HFE), enhanced iron uptake, an increase in nonheme iron content, and accentuated ILI response for NF-kappaB activation in KC. Ex vivo treatment of these KC with an iron chelator abrogates the increment of iron content, ILI response, and NF-kappaB activation. The ILI response is evident in macrophages derived from human blood monocytes by PMA treatment but not in vehicle-treated monocytes, and this differentiation-associated phenomenon is essential for maximal TNF-alpha release. PMA-induced macrophages load iron dextran and enhance ILI response and TNF-alpha release. These effects are reproduced in KC selectively loaded in vivo with iron dextran in mice and more importantly aggravate experimental ALD. Our results suggest enhanced iron uptake as a mechanism of KC iron loading in ALD and demonstrate the ILI response as a function acquired by differentiated macrophages in humans and as a priming mechanism for ALD.

We evaluated the usefulness of PGE2 on chemotherapy-associated oral mucosal lesions of the patients with hematological malignancies and compared the efficacy of the troche with that of the tablet. One hundred and fifty three patients were given 0.5 mg of these PGE2 topically three times daily. One hundred and fourty five cases were evaluable (Tablet; 85, Troche; 60). 1) Symptoms and signs were improved in 102/144 (70.8%) and 102/145 (70.3%), respectively. The overall response rate was 70.3%. 2) The improvement rates were 77.5% (55/71), 85.7% (6/7) and 62.7% (32/51) in leukocyte count-increased, -unchanged and -decreased patients, respectively. 3) No background factor of the patients except performance status affected the improvement rate. 4) Higher improvement rate was noted in the PGE2 early starting group (within 5 days after the appearance of oral lesions) than the late group (6 days and thereafter) (76.5% v.s. 55.8%: U-test p less than 0.1, chi2-test p less than 0.05). 5) There was no difference in the efficacy rate between the tablet and the troche. 6) Mild side effects were seen in 10 cases. These results suggest that topical administration of PGE2 is safe and useful for improving chemotherapy-associated oral mucosal lesions of patients with hematological malignancies.

To evaluate the effects of short-term starvation on gastric emptying in normal and obese subjects, the relationship between gastric emptying and oral glucose tolerance, and the mechanisms responsible for the delay in the systemic appearance of oral glucose observed after short-term fasting, we determined the effects of a 4-day fast on 1) gastric emptying and oral glucose tolerance in normal subjects and 2) gastric emptying in obese patients. Gastric emptying of 75 g glucose (320 ml) labeled with 99mTc colloid was measured in 12 healthy volunteers and 11 obese subjects after 12-h and 4-day fasts. In seven other obese subjects, the effect of a 4-day fast on gastric emptying of 320 ml normal saline was quantified. Gastric emptying of glucose was slower after the 4-day than after the overnight fast in both normal (P = 0.02) and obese (P < 0.001) subjects, with no difference between the two groups. In normal subjects, the rate of gastric emptying was related directly to the rise in plasma glucose at 30 min (r = 0.60; P < 0.05) but inversely to the plasma glucose at 180 min (r = -0.64; P < 0.02). In the obese subjects, gastric emptying of saline was not affected by fasting. These observations indicate that 1) gastric emptying of glucose is retarded by a 4-day fast, 2) the changes in gastric emptying reported in obesity may reflect different patterns of prior nutrient intake, and 3) delay in gastric emptying accounts for the slower systemic appearance of glucose after fasting.

Experiments were performed to test the effects of frequency and stretch on the velocity of slow wave propagation parallel and perpendicular to the long axis of circular muscle fibers in the canine gastric antrum. Slow waves were evoked from one corner of a rectangular sheet of muscle and propagated throughout the tissue. Mathematics were derived and are presented, which simultaneously compute conduction velocities in each direction, regardless of electrode positions. Increased rate of stimulation had no significant effect on conduction velocity in the circumferential axis, but propagation slowed in the axis perpendicular to the circular fibers by an average of 25% over interstimulus intervals between 12 and 60 s. Conduction velocity was also a function of the degree of stretch. The most rapid conduction velocity occurred when muscles were stretched to an average of 118% of the resting, fasted length found in situ in the axis parallel to the circular fibers and 140% in the axis perpendicular to the circular fibers. Propagation was blocked by stretching muscles past 200% of resting length. These results suggest that the frequency of slow waves and gastric distension are intrinsic mechanisms capable of regulating the spread of slow waves.

To evaluate the hemorrhage rates of cerebral arteriovenous malformations (AVM) and the risk factors of hemorrhage before and after Gamma Knife radiosurgery (GKS). The annual hemorrhage rate was calculated as the number of hemorrhages divided by the patient-years at risk. Characteristics of patients and AVM related to hemorrhagic or nonhemorrhagic presentation were evaluated by logistic regression. Risk factors predicting AVM hemorrhage during the period from the diagnosis to GKS of AVM and during the latency period after radiosurgery were evaluated using Cox regression hazards model. The annual hemorrhage rate before GKS was 2.0% assuming patients were at risk for hemorrhage since their birth. The hemorrhage rate calculated between the diagnosis and GKS of AVM was 6.6% and reduced to 2.5% after GKS until obliteration of the AVM. Although small and deep nidi and those with deep and single draining veins tended to present themselves with hemorrhage, only nidi with single draining veins and those ruptured before were more likely to bleed once the AVM had been diagnosed. These factors no longer predisposed the nidus to a rupture after radiosurgery and the only predicting factor for hemorrhage was a low radiosurgical prescription dose to the margin of nidus. The AVM hemorrhage rate seems to reduce after GKS. After radiosurgery, none of the patients or nidus-related risk factors remained relevant to the occurrence of hemorrhage. The nidus treated with a high radiosurgical dose is less likely to bleed.

Liver ischemia-reperfusion (I/R) injury is associated with profound arginine depletion due to arginase release from injured hepatocytes. The purpose of this study was to determine whether arginase inhibition with N(omega)-hydroxy-nor-l-arginine (nor-NOHA) would increase circulating arginine levels and decrease hepatic damage during liver I/R injury. The effects of nor-NOHA were initially tested in normal animals to determine in vivo toxicity. In the second series of experiments, orthotopic syngeneic liver transplantation (OLT) was performed after 18 h of cold ischemia time in Lewis rats. Animals were given nor-NOHA (100 mg/kg) or saline before and after graft reperfusion. In normal animals treated with nor-NOHA, there were no histopathological changes to organs, liver enzymes, serum creatinine, or body weight. In the OLT model, animals treated with saline exhibited markedly elevated serum transaminases and circulating arginase protein levels. Nor-NOHA administration blunted the increase in serum arginase activity by 80% and preserved serum arginine levels at 3 h after OLT. Nor-NOHA treatment reduced post-OLT serum liver enzyme release by 50%. Liver histology (degree of necrosis) in nor-NOHA-treated animals was markedly improved compared with the saline-treated group. Furthermore, use of the arginase inhibitor nor-NOHA did not influence polyamine synthesis owing to the decrease in ornithine levels. Arginase blockade represents a potentially novel strategy to combat hepatic I/R injury associated with liver transplantation.

Regular aerobic exercise has numerous benefits on human physiology, arguably by serving as a hormetic stressor resulting in positive adaptations over time. It has long been known that aerobic exercise at a variety of intensities and durations induces intestinal permeability, which is a feature of many pathologies of the gastrointestinal tract and metabolic diseases. Given the health benefits of exercise, it seems unlikely that intestinal permeability induced by exercise outweighs the positive adaptations. In fact, a growing body of evidence suggests adoption of exercise regimens lasting weeks to months improves indicators of intestinal permeability. In this brief review, we summarize factors contributing to acute exercise-induced intestinal permeability and what is known about chronic exercise and the gut barrier. Additionally, we outline known and theoretical adaptations of the gut to chronic exercise that may explain emerging reports that exercise improves markers of gut integrity.

In rat hepatocytes, basolateral Na(+)-H+ exchange and Na(+)-HCO3- cotransport function as acid extruders. To assess mechanisms of acid loading, intracellular pH (pHi) recovery from an alkaline load was analyzed in short-term cultured rat hepatocyte monolayers using the pH-sensitive dye BCECF. Electrophysiological techniques were also used to assess the role of the membrane potential (Vm). Cells were alkaline loaded by suddenly reducing external CO2 and HCO3- (from 10% and 50 mM, respectively, to 5% and 25 mM) at constant pHo. After this maneuver, pHi rapidly rose by 0.13 +/- 0.03 pH units (pHu) and recovered to baseline at an initial rate of 0.026 +/- 0.009 pHu/min. Intracellular buffering power was estimated from the dependence of pHi on [NH4+]o and varied between 70 and 10.5 mM/pHu in a pHi range of 6.5-7.6. Initial pHi recovery corresponded to a rate of OH- efflux (JOH) of 1.76 +/- 0.71 mM/min and was blocked by 0.5 mM DIDS (0.003 +/- 0.002; JOH = 0.18 +/- 0.06) or by 1 mM H2DIDS (0.001 +/- 0.002; JOH = 0.26 +/- 0.08) and by removal of [Cl-]o (0.003 +/- 0.007; JOH = 0.28 +/- 0.07). The dependence of JOH on [Cl-]o exhibited saturation kinetics with an apparent Km for [Cl-]o of 5.1 mM. pHi recovery was Na+ independent and was not inhibited by substitution of Na+ with NMDG (0.045 +/- 0.09; JOH = 2.94 +/- 0.59). During an alkaline load, cell Vm hyperpolarized from -33.4 +/- 1.8 to -43.4 +/- 2.8 mV, mainly due to an increase in K+ conductance by a factor of 2.8 +/- 0.3.(ABSTRACT TRUNCATED AT 250 WORDS)