Effects of the rate and composition of fluid replacement on the pharmacokinetics and pharmacodynamics of intravenous furosemide

Effects of differences in the rate and composition of intravenous fluid replacement for urine loss on the pharmacokinetics and pharmacodynamics of furosemide were evaluated using the dog as a model animal. Each of six dogs received 8-hr constant intravenous infusion of 20 mg (15 mg used in one dog) of furosemide with 0% replacement (treatment I), 50% replacement (treatment II), and 100% replacement (treatment III) with lactated Ringer's solution, as well as with 100% replacement with 5% dextrose in water (treatment IV). Most pharmacokinetic parameters, such as plasma clearance, steady-state volume of distribution, mean residence time, and terminal half-life, were essentially the same in all four treatments. Renal clearances and urinary excretion rates of the drug in treatments II–IVwere essentially the same, but about 20% higher than those in treatment I.In spite of the similarities in kinetic properties, diuretic and/or natriuretic effects from furosemide were markedly different among the four treatments. For example, mean 10-hr urine outputs were 646, 1046, 3156, and 1976 ml and mean 10-hr sodium excretions were 87.0, 142, 383, and 97.2 mmole for treatments I–IV,respectively. Except for treatment III,diuresis and/or natriuresis were found to be time-dependent, generally decreasing with time until reaching a low plateau during later hours of infusion. The present findings also showed that (1)no fluid replacement and 100% replacement with 5% dextrose solution both produced the same degree of severe acute tolerance in natriuresis, indicating the insignificance of water compensation in tolerance development; (2)in treatment II,where neutral sodium balance was achieved, the development of acute tolerance in diuresis and natriuresis can mainly be attributed to negative water balance under this special condition; (3)at steady state the hourly diuresis and natriuresis could differ up to about ten times between treatments. Some implications for the kinetic/dynamic relationship or modeling, in the clinical use, and in the bioequivalence evaluation of dosage forms are discussed.     

“津血同源”“肾为唾”的研究

以23例肾功能不全与20例肾功正常患者的唾液尿素氮、钠、钾、舌面pH值和血液的相应生化检查作对照。结果唾液尿素氮、钾与血尿素氮、钾成正相关性。证实了中医“津血同源”“肾为唾”的理论。     

中性粒细胞在高浓度氧诱发急性肺损伤中的作用

目的:测定鼠支气管肺泡清洗液中细胞成分,阐明高浓度氧诱发急性肺损伤的发生机制。方法:20只雄性6周龄[(226±53.6)g]Wistar鼠被分为3组:(1)对照组(空气中饲养,n=6)。(2)实验组1(暴露在90%～95%氧气中24～48h,n=7)。(3)实验组2(暴露在90%～95%氧气中72h,n=7)。实验中动物可自由进食和水。结果:与对照组相比,实验组2的支气管肺泡清洗液中总细胞数减少[(3.81±0.35)×105/ml,(2.53±0.77)×105/ml];巨噬细胞数减少[(3.80±0.36)×105/ml,(2.09±0.59)×105/ml];而中性粒细胞计数明显增多[0,(43.56±42.63)×103/ml]。实验组2的动物都出现双侧胸水。结论:中性粒细胞动员并进入肺组织是高浓度氧诱发急性肺损伤的明显特征,损伤的发生与暴露时间有关。提示早期抑制中性粒细胞进入肺组织是治疗高浓度氧诱发急性肺损伤的重要途径。     

Free amino acid pattern of cerebrospinal fluid in meningeal pathology

Free amino acid concentrations of CSF were measured in bacterial meningitis, aseptic meningitis, meningoradiculitis Garin-Bujadoux-Bannwarth, multiple sclerosis, carcinomatous meningitis, and controls. Almost all CSF amino acids were highly elevated in bacterial but not in aseptic meningitis, meningoradiculitis Garin-Bujadoux-Bannwarth or carcinomatous meningitis thus providing a laboratory tool for their differential diagnosis. In carcinomatous meningitis the amino acid pattern indicates metabolic activity of tumor cells. Minimal alterations were found in multiple sclerosis which have no diagnostic value.     

Intrathecal synthesis of IgG subclasses in multiple sclerosis and in acquired immunodeficiency syndrome (AIDS)

Serum and cerebrospinal fluid (CSF) of 50 neurological patients (24 multiple sclerosis (MS), ten acquired immunodeficiency syndrome (AIDS) and 16 other neurological diseases (OND)) and ten controls were analyzed by enzyme-linked immunosorbent assay (ELISA) for IgG subclass quantification and for the calculation of intrathecal synthesis (ITS). Total IgG was determined by two methods: electroimmunodiffusion (EID) and ELISA. A highly significant correlation was established between both methods. The existence of ITS was proved by the IgG/albumin ratio, the IgG index, Tourtellotte's formula, and Schuller's formula. In AIDS patients all IgG subclasses showed an increase in the CSF, whereas in sera only the IgG1 was significantly increased. CSF of MS patients showed a predominant increase of IgG1 whereas no significant modification of IgG subclasses was observed in sera. In most of the AIDS patients there was an ITS of IgG1, IgG3 and IgG4, but rarely (3/10) IgG2. In contrast, a polyclonal ITS of IgG was exceptional (1/24) in MS patients. No significant correlation could be established between clinical data and IgG subclass ITS in MS. The variations of each IgG subclass in serum and in ITS were not significantly correlated. Measurement of each IgG subclass and calculation of ITS seems essential in order to analyze any subclass antibody repertory inside the central nervous system.     

关节液检查的临床意义

检查30例关节炎患者的关节液,结果示类风湿性关节炎患者关节液中白细胞数为330～72600/mm~3,粒细胞为9～97％,结合关节液的其它物理性质,对类风湿关节炎的诊断有一定参考价值。并观察到类风湿关节炎患者血清中IgG、IgA、IgM和关节液中IgG高于其它类型关节炎。     

Characterization of ramified microglia in tissue culture: pinocytosis and motility

Functional properties of ramified microglia were investigated in primary cultures of rat cerebral cortical cells. These microglia could be readily identified in both fixed and living cultures through previously established features. Based on their destruction by 5 mM L-leucine methyl ester, a high level of intrinsic endocytotic activity was established. When cultures were incubated with fluorescent latex beads to assess phagocytosis, little or no such activity was exhibited by ramified cells. However, when cultures were incubated with dyes or other soluble tracer compounds, these cells always exhibited labeling. This labeling was selective for ramified microglia in the cultures and was demonstrated using a variety of compounds, including trypan blue, lucifer yellow, horseradish peroxidase (HRP), and India ink. Intracellular label could be observed in vesicular structures; this localization corresponded to an active cellular process. Also, cellular labeling was inhibited by the presence of colchicine. These features supported the inference that the labeling was attributable to pinocytosis, and this process appeared to account for the vast majority of endocytotic activity in the ramified microglia. Possible physiological significance of this pinocytotic activity was indicated by the accumulation of various neurotransmitters/modulators: gamma-aminobutyric acid and vasoactive intestinal polypeptide (VIP). Ramified cells in these cultures have been previously noted to exhibit a constant and rapid pattern of motility, which was consistently observed here through time-lapse video recording; pinocytosis and rapid motility were shown to concur in individual cells. Based on their high intrinsic pinocytotic activity and pattern of cellular motility, the ramified microglia specifically are suggested to serve a constitutive function of fluid cleansing within the interstitial spaces of brain tissue.     

Guillain–Barré syndrome with marked pleocytosis or a significant proportion of polymorphonuclear granulocytes in the cerebrospinal fluid: neuropathological investigation of five cases and review of differential diagnoses

In cases with otherwise clinically typical Guillain-Barré syndrome (GBS), pronounced cerebrospinal fluid (CSF) pleocytosis or the mere presence of CSF-polymorphonuclear granulocytes should alert the physician to consider alternative diagnoses. Therefore, we retrospectively studied the neuropathology of central and peripheral nervous system in two cases with a CSF cell count of more than 50/microl and in three cases with a significant proportion of polymorphonuclear granulocytes in the CSF sediment. All cases fulfilled the required criteria for the diagnosis of GBS, the duration from onset to death ranged from 4 to 100 days. Neuropathological investigations included routine staining procedures and immunohistochemistry for antigens of glial and haematopoetic cells as well as for products of relevant neurotropic viruses. Demyelinating polyradiculitis was present in four cases, in one patient with a survival time of 4 days the type of damage to myelinated fibres was unclassifiable. In the central nervous system a consistent finding was diffuse activation of microglia, only one case showed mild meningeal and lower brainstem inflammation. Viral products were generally absent. In summary, the neuropathological findings confirm that marked CSF pleocytosis or the presence of polymorphonuclear granulocytes does not rule out the diagnosis of GBS.     

Plasma atrial natriuretic peptide (ANP) concentration and fluid balance during rapid intravenous saline infusions in camels

Human muscle samples were obtained with the percutaneous biopsy technique. The samples were membrane-hyperpermeabilized (skinned) using a chemical or freeze-drying technique. Short single fibre segments were dissected from the sample, transferred to an experimental chamber, connected to a force transducer and manipulator, and exposed to temperature-controlled solutions. The force generating-capacity, the sensitivity of the contractile apparatus to calcium and the caffeine threshold for calcium release from the sarcoplasmic reticulum could be studied in the short muscle fibre segments obtained from man with the percutaneous muscle biopsy technique. The average length of the fibre segments between the connectors was 0.44±0.21 mm. Thus, detailed studies of the contractile machinery can be made on human skinned muscle fibres with only minimal discomfort to the patient or subject during biopsy, which should be useful in studies of neuromuscular disease, muscle plasticity or in applied physiology.     

Soluble Fcγ receptors in periodontal lesions

Soluble Fcγ-binding components were detected in gingival fluid from periodontal lesions by incubation with biotinylated human Fcγ fragments. FcγIII receptor was identified by incubation of gingival fluid with monoclonal antibody. Sodium dodecyl sulfate-polyacrylamide gel electophoresis and Western transfer showed that most of the Fcγ-binding components had minimal mobility in a 4–15% gradient gel under nonreducing conditions. Under reducing conditions, the main band of Fcγ-binding components in gingival fluid migrated corresponding to protein A of 49 kDa. The pattern of Fcγ-binding components was similar in serum and gingival fluid except for the observation in gingival fluid of Fcγ-binding components migrating like standard proteins of 19 to 20 kDa, a size that corresponds to the polypeptide part of FcγII receptor and FcγIII receptor.