PMA Group Research Articles

Neuroprotective effects of ulinastatin on Escherichia coli meningitis rats through inhibiting PKCα phosphorylation and reducing zonula occludens-1 degradation

Ulinastatin, a broad-spectrum inflammatory inhibitor widely employed in the management of severe pancreatitis and sepsis, has not been extensively investigated for its therapeutic potential in bacterial meningitis. This study aims to assess the neuroprotective effects of ulinastatin on bacterial meningitis and elucidate its underlying mechanism. The rat model of bacterial meningitis was established by intracerebral injection of Escherichia coli. 3-week-old SD rats were randomly divided into 5 groups with 8 rats in each group, including control group, E.coli group, E.coli + UTI group (ulinastatin 50000IU/kg), E.coli + UTI + PMA group (ulinastatin 50000IU/kg + PMA 200 ug/kg), and E.coli + PMA group(PMA 200 ug/kg). Behavioral changes were assessed by Loeffler neurobehavioral score. Histomorphologic changes and apoptosis were assessed by hematoxylin and eosin staining, Nissl staining and TUNEL staining. Immunohistochemistry and immunofluorescence and western blotting were used to detect the expression levels of zonula occludens-1 (ZO-1) and phosphorylation protein kinase C (PKCα).It was found that ulinastatin treatment in Escherichia coli meningitis rats improved neurological function, alleviated meningeal inflammatory infiltration, reduced neuronal death, promoted the integrity of the blood–brain barrier structure. Moreover, phorbol myristate acetate (PMA, a protein kinase C activator), blocked the effective action of ulinastatin. These findings suggest that ulinastatin had neuroprotective effects on bacterial meningitis by inhibiting PKCα phosphorylation and reducing ZO-1 degradation, demonstrating that ulinastatin may be a promising strategy in the treatment of bacterial meningitis.

CircRNA_0050486 promotes cell apoptosis and inflammation by targeting miR-1270 in atherosclerosis.

BackgroundAtherosclerosis (AS) is a chronic inflammatory disease that plays a major role in cardiovascular disease. Circular RNAs (circRNAs) are related to the pathogenesis of AS, including the inflammatory response. This study aimed to explore the underlying mechanisms of circRNAs and how they regulate the inflammatory response in AS.MethodsAnalyzed the expression profile of circRNAs in three oxidized low-density lipoprotein (oxLDL) treated macrophage samples and three macrophage control samples using bioinformatics methods. Expression and biological function of circRNA were verified in oxLDL-induced THP-1 macrophages. MiRNAs and target genes of circRNA were predicted by functional enrichment analysis. Expression and function of circRNA target miRNAs were explored in oxLDL-induced THP-1 macrophages. Finally, we predicted and analyzed the function of circRNAs-miRNAs target genes in AS.ResultsWe identified nine upregulated circRNAs and found that circ_0050486 was significantly upregulated in a THP-1 + PMA + oxLDL group compared with a THP-1 + PMA group. Additionally, circ_0050486 knockdown markedly inhibited IL-6 and TNF-α concentrations and the cell death rates in oxLDL-induced THP-1 macrophages. Furthermore, circ_0050486 targeted and inhibited miR-145 and miR-1270. Upregulated miR-1270 markedly inhibited IL-6 and TNF-α levels and the cell death rates in oxLDL-induced THP-1 macrophages. Finally, the target genes of miR-1270 and miR-145 were predicted by the miRDB, miRWalk, and Targetscan databases, and a functional analysis network of the target genes was constructed by Cytoscape GlueGO, including the regulation of the immune response and monocyte chemotaxis. The common target genes of miR-145 and miR-1270 were established by Cytoscape and included NF1A, among others.ConclusionsOur study suggested that circ_0050486 knockdown inhibited inflammation and apoptosis by targeting miR-1270 in oxLDL-induced THP-1 macrophages. This finding may provide a potential therapeutic target for atherosclerosis.

Changes of heparin-binding protein in severe burn patients during shock stage and its effects on human umbilical vein endothelial cells and neutrophils

Changes of heparin-binding protein in severe burn patients during shock stage and its effects on human umbilical vein endothelial cells and neutrophils

Triptolide inhibits neutrophil extracellular trap formation.

BackgroundTriptolide (PG490), as a triterpene dicyclic oxide has been reported to increase the generation of reactive oxygen species (ROS) and nitric oxide (NO) and induce apoptosis of RAW 264.7 cells in a dose-dependent manner. The activity of death NETs plays an important role in anti-bacterial processes in the human body. This study aimed to investigate the effect of triptolide (PG490) on neutrophil extracellular traps (NETs) formation.MethodsAfter isolating peripheral blood neutrophils from healthy volunteers, cells were incubated with PG490 to observe and detect the level of NETs and detect the level of reactive oxygen species (ROS). The cells were cultured, stained and analyzed by fluorescence microscopy.ResultsCompared with the 12-myristate-13-acetate (PMA) group, the average fluorescence intensity of SYTOX Green in the PG490 + PMA group, as detected by a multifunctional microplate reader, was significantly decreased. Intracellular ROS were labeled by fluorescence, with fluorescence intensity then measured by multifunctional microplate reader and flow cytometry. The results showed that compared with the control group, the fluorescence intensity of the PMA group was significantly increased, while there was no significant difference between PMA group and PG490 + PMA group.ConclusionsThe production of NETs is inhibited by PG490 in vitro, which is not associated with the level of cellular ROS. This suggests that PG490in Tripterygium wilfordii Hook F can suppress related diseases.

Role of PKCα/HO-1 signaling pathway in endotoxin-induced damage to alveolar macrophages of rats: the relationship with mitofusin-1

Objective To evaluate the role of protein kinase C α (PKCα)/heme oxygenase-1 (HO-1) signaling pathway in endotoxin-induced damage to alveolar macrophages and the relationship with mitofusin-1 (Mfn1) in rats. Methods Rat alveolar macrophages NR8383 cells cultured in vitro were seeded in 96-well plates at a density of 1×104 cells/ml.NR8383 cells were divided into 5 groups (n=15 each) using a random number table: control group (group C), endotoxin challenge model group (group E), PKCα inhibitor Go6976 group (group G), PKCα agonist PMA group (group P) and dimethyl sulfoxide group (group D). NR8383 cells were stimulated with 10 μg/ml lipopolysaccharide (LPS) to establish the model of endotoxin challenge in alveolar macrophages.In G, P and D groups, cells were pretreated with 5 μmol/L Go6976, 100 nmol/L PMA and 0.1% dimethyl sulfoxide, respectively, for 30 min starting from 30 min before stimulation with LPS, and 10 μg/ml LPS was then given.The cells were collected after 24 h of incubation for measurement of malondialdehyde (MDA) and reactive oxygen species (ROS) contents, superoxide dismutase (SOD) activity and expression of PKCα, HO-1 and Mfn1 protein and mRNA (by fluorescent quantitative polymerase chain reaction or Western blot). Results Compared with group C, MDA and ROS contents were significantly increased, the SOD activity was decreased, the expression of PKCα and HO-1 protein and mRNA was up-regulated, and the expression of Mfn1 protein and mRNA was down-regulated in E, G, P and D groups (P 0.05). Conclusion Promotion of Mfn1 expression following PKCα/HO-1 signaling pathway activation is the endogenous protective mechanism of endotoxin-induced damage to alveolar macrophages of rats. Key words: Protein kinase C-alpha; Heme oxygenase-1; Endotoxins; Mitochondrial proteins; Membrane fusion proteins

Papillary Muscle Approximation Versus Restrictive Annuloplasty Alone for Severe Ischemic Mitral Regurgitation

BackgroundGuidelines recommend surgery for patients with severe ischemic mitral regurgitation (MR). Nonrandomized studies suggest that subvalvular repair is associated with longer survival, but randomized studies are lacking. ObjectivesThis study sought to investigate the benefit of papillary muscle surgery on long-term clinical outcomes of patients with ischemic MR. MethodsNinety-six patients with severe ischemic MR were randomized to either undersizing restrictive mitral annuloplasty (RA) or papillary muscle approximation with undersizing restrictive mitral annuloplasty (PMA) associated with complete surgical myocardial revascularization. The primary endpoint was change in left ventricular end-diastolic diameter (LVEDD) after 5 years, measured as the absolute difference from baseline, which was evaluated by paired Student t tests. Secondary endpoints included changes in echocardiographic parameters, overall mortality, the composite cardiac endpoint (major adverse cardiac and cerebrovascular events [MACCE]), and quality of life (QOL) during the 5-year follow-up. ResultsAt 5 years, mean LVEDD was 56.5 ± 5.7 mm with PMA versus 60.6 ± 4.6 mm with RA (mean change from baseline −5.8 ± 4.1 mm and −0.2 ± 2.3 mm, respectively; p < 0.001). Ejection fraction was 44.1 ± 6% in the PMA group versus 39.9 ± 3.9% in the RA group (mean change from baseline 8.8 ± 5.9% and 2.5 ± 4.3%, respectively; p < 0.001). There was no statistically significant difference in mortality at 5 years, but freedom from MACCE favored PMA in the last year of follow-up. PMA significantly reduced tenting height, tenting area, and interpapillary distance soon after surgery and for the long-term, and significantly lowered moderate-to-severe MR recurrence. No differences were found in QOL measures. ConclusionsCompared with RA only, PMA exerted a long-term beneficial effect on left ventricular remodeling and more effectively restored the mitral valve geometric configuration in ischemic MR, which improved long-term cardiac outcomes, but did not produce differences in overall mortality and QOL.

Effect of deformation and temperature on the ordering of polyimide PM-A molecules. X-ray data

X-ray diffractometry is used to study samples of type PM-A group B polyimide (Kapton H) subjected to uniaxial tension at room temperature and cooling to liquid nitrogen and helium temperatures. An asymmetry in the halo of the diffraction pattern from the amorphous sample is observed as a result of deformation and cooling of the samples. Deformation and cooling are found to have different effects on the intensity distribution. Thus, deformation produces “stretched” regions, while cooling produces “compressed” regions. An analysis of the diffraction patterns shows that uniaxial tension leads to partial ordering of the polyimide molecules in a sample along the direction of the applied load. The observed changes in the structure during cooling of films may indicate that mutual ordering of some of the molecules relative to one another is taking place.

Antiarrhythmic peptide AAP10 prevents arrhythmias induced by protein kinase C activation in rabbit left ventricular wedges.

As the mechanisms underlying PKC activation induced arrhythmias are not yet fully verified, we investigated the role of gap junctions in arrhythmias induced by PKC activation.Arterially-perfused rabbit left ventricular preparations were randomly assigned to perfusion with phorbol ester (PMA) or in combination with AAP10. Transmural ECG as well as action potentials from both endocardium and epicardium were simultaneously recorded throughout all experiments. Changes in connexin43 (Cx43) and nonphosphorylated Cx43 on S368 were measured by Western blot analysis.In the PMA group, the QT interval was shortened, the interval from the peak to the end of the electrocardiographic T wave (Tp-e) and induced nonsustained ventricular tachycardia (VT) were increased, and the expressions of Cx43 and nonphosphorylated Cx43 on S368 were decreased compared with the control group. Compared with the PMA group, without significant changes in the QT interval and the expression of nonphosphorylated connexin43 on S368, Tp-e and induced VT decreased and the expression of Cx43 increased in the AAP10 group.AAP10 can prevent PMA-induced rabbit ventricular arrhythmias by attenuating the increase of Tp-e and the decrease of expression of Cx43. These data suggest that increasing gap junction coupling prevents arrhythmias induced by protein kinase C activation.

Evaluation of immunopathologic effects of aqueous extract of Echinacea purpurea in mice after experimental challenge with Pasteurella multocida serotype A.

In order to assess the immunopathological effects of aqueous Echinacea purpurea extract (EPE) on mice experimentally challenged with Pasteurella multocida serotype A, forty female BALB/c mice were randomly divided into four groups. The groups included a control group (received sterile distilled water 2 times/week for 2 weeks, intraperitoneally and then 100 µl sterile saline intranasally), a PMA group (received sterile distilled water as the control group and after 2 weeks, 5.6 × 10(3) CFU/ml of P. multocida serotype A, intranasally), an EPE+PMA group (received E. purpurea extract intraperitoneally 2 times/week for 2 weeks and then challenged as the PMA group) and an EPE group (received E. purpurea extract as EPE+PMA group and then 100 µl sterile saline intranasally). After 24 and 48 h post challenge, half of the animals in each group were sacrificed and analyzed for bacterial counts in their lungs and livers, TNFα serum levels and histapathological changes. The results showed significant differences in lung bacterial counts between PMA and EPE+PMA groups. TNFα serum level was significantly higher in the PMA group. Histopathological examination revealed infiltration of neutrophils in alveolar septa and hyperemia in the PMA group. In addition, the criteria of bronchopneumonia were partially recovered in the EPE+PMA compared to the PMA group. According to the results, it seems that E. purpurea extract has an immunomodulatory effect and can be used to prevent or control of pneumonia caused by Pasteurella.

Differential motor neuron involvement in progressive muscular atrophy: a comparative study with amyotrophic lateral sclerosis

ObjectiveProgressive muscular atrophy (PMA) is a clinical diagnosis characterised by progressive lower motor neuron (LMN) symptoms/signs with sporadic adult onset. It is unclear whether PMA is simply a clinical phenotype...

Efficacy and safety of methylcobalamin, alpha lipoic acid and pregabalin combination versus pregabalin monotherapy in improving pain and nerve conduction velocity in type 2 diabetes associated impaired peripheral neuropathic condition. [MAINTAIN]: Results of a pilot study.

Background and Objective:To assess whether methylcobalamin and alpha lipoic acid (ALA) added to pregabalin provide additional benefit compared to pregabalin alone in type 2 diabetes mellitus associated peripheral neuropathy.Setting and Design:An open label, randomized, controlled parallel-group pilot study.Materials and Methods:Thirty adult patients with type 2 diabetes mellitus with symptoms of peripheral neuropathy for ≥6 months were randomized to receive pregabalin 75 mg, methylcobalamin 750 μg, and ALA 100 mg (PMA, n = 15); or pregabalin 75 mg (PG, n = 15) for 12 weeks. Assessment variables were numeric rating scale (NRS), sleep interference scores (SIS), response rate to pain, and global assessment for the usefulness of therapy. The nerve conduction velocity was assessed for sensory and motor nerves. Safety assessment included adverse events reported by the patients, clinical laboratory, and general medical, neurological examinations.Statistical Analysis:Efficacy analyses were done on per-protocol (PP) population, whereas safety analyses were done on intent-to-treat (ITT) population.Results:Significant improvement was seen in pain and sleep interference in both groups. Mean nerve conduction velocity of left common peroneal nerve (CPN) showed significant improvement in PMA group at week 12 compared to baseline (P = 0.018). For right CPN both groups showed significant improvement. (PMA, P = 0.002, PG, P = 0.007). For sensory testing, at week 12, right superficial peroneal nerve showed reduction in nerve conduction velocity in PG group compared to baseline (P = 0.043).Conclusion:Methylcobalamine, ALA and pregabalin combination provides pain relief and improves sleep interference. Addition of methylcobalamin and ALA to pregabalin improves the nerve function. Due to small sample size, most of the efficacy parameters could not reach significant difference between groups; hence benefit of the 3-drug-combimation should be interpreted with reservation.

Efficacy and safety of methylcobalamin, alpha lipoic acid and pregabalin combination versus pregabalin monotherapy in improving pain and nerve conduction velocity in type 2 diabetes associated impaired peripheral neuropathic condition. [MAINTAIN]: Results of a pilot study.

Background and Objective: To assess whether methylcobalamin and alpha lipoic acid (ALA) added to pregabalin provide additional benefit compared to pregabalin alone in type 2 diabetes mellitus associated peripheral neuropathy. Setting and Design: An open label, randomized, controlled parallel-group pilot study. Materials and Methods: Thirty adult patients with type 2 diabetes mellitus with symptoms of peripheral neuropathy for ≥6 months were randomized to receive pregabalin 75 mg, methylcobalamin 750 μg, and ALA 100 mg (PMA, n = 15); or pregabalin 75 mg (PG, n = 15) for 12 weeks. Assessment variables were numeric rating scale (NRS), sleep interference scores (SIS), response rate to pain, and global assessment for the usefulness of therapy. The nerve conduction velocity was assessed for sensory and motor nerves. Safety assessment included adverse events reported by the patients, clinical laboratory, and general medical, neurological examinations. Statistical Analysis: Efficacy analyses were done on per-protocol (PP) population, whereas safety analyses were done on intent-to-treat (ITT) population. Results: Significant improvement was seen in pain and sleep interference in both groups. Mean nerve conduction velocity of left common peroneal nerve (CPN) showed significant improvement in PMA group at week 12 compared to baseline (P = 0.018). For right CPN both groups showed significant improvement. (PMA, P = 0.002, PG, P = 0.007). For sensory testing, at week 12, right superficial peroneal nerve showed reduction in nerve conduction velocity in PG group compared to baseline (P = 0.043). Conclusion: Methylcobalamine, ALA and pregabalin combination provides pain relief and improves sleep interference. Addition of methylcobalamin and ALA to pregabalin improves the nerve function. Due to small sample size, most of the efficacy parameters could not reach significant difference between groups; hence benefit of the 3-drug-combimation should be interpreted with reservation.

Role of L- and T-Type Calcium Channels in Regulation of Absence Seizures in Wag/Rij Rats

In chronic experiments on five groups of WAG/Rij rats (a genetic model of absence epilepsy; six animals in each group), we recorded EEG activity from the S1po cortical area through implanted electrodes and subjected the cortex to the action of four agents affecting L- and T-type calcium channels (injections through an implanted cannula). A blocker of L-type channels, verapamil hydrochloride, an agonist of these channels, Bay K8644, an antagonist of T-type calcium channels, L-ascorbate, and an agonist of the latter channels, PMA, were used. The parameters of 7- to 10-Hz spike-wave discharges, SWDs, spontaneously generated in the cortex of this rat strain (frequency within SWDs, mean duration of the latter, and their number) were measured within the baseline interval (before injections) and within three subsequent 20-min-long post-injection intervals. Normal saline was injected in the control group. There were no significant differences in the mean peak frequency in SWDs between all examined groups (P > 0.05 in all cases). Verapamil significantly (by more than 40%; P < 0.05) decreased the mean SWD duration throughout the entire period of post-injection observation. The dynamics of the Bay K8644 effects were rather similar, but the intensity of SWD duration changes was somewhat smaller. Both the above agents in the doses used dramatically decreased the number (frequency of appearance) of SWDs within the observation period. L-ascorbate also suppressed SWD generation. The duration of these phenomena decreased mildly, while their number dropped dramatically. In the PMA group, the number of SWDs increased significantly (by 50%, P < 0.05) within the first 20-min-long interval, but this was not observed within subsequent intervals. These findings confirm that blocking or activating of L- and T-type Ca2+ channels in the S1po area (cortical focus area) can significantly control generation of SWDs during absence seizures. Possible mechanisms underlying actions of the tested agents are discussed.

The Role and Regulation mechanism of the phosphorylation of VASP in the Changes of Cytoskeleton Induced by ox‐LDL in Endothelial Cells

The state and distribution of the cytoskeleton are intimately related to the endothelial integrity. Vasodilator stimulated phosphoprotein (VASP) is a crucial regulator of actin which is identified as main component of microfilaments in cytoskeleton. Activated PKC can induce VASP phosphorylation. It is reported that ox-LDL can activate PKC pathway in endothelial cells through the specific receptor binding. In order to investigate the role of VASP phosphorylation in ox-LDL-induced changes of cytoskeleton in endothelial cell and identify whether PKC participates the phosphorylation of VASP induced by ox-LDL, the endothelial cell line (ECV304) was divided into 6 groups with different condition, which including the Control (normal culture), PKC activator(PMA 0.1μM), PKC inhibitor (GF109203X 1μM), ox-LDL(200μM), PMA+ox-LDL group, and GF109203X+ox-LDL group. We observed that the formation of stress fiber increased in ox-LDL, PMA and ox-LDL+PMA groups, but actin clustered in the peripheral region of the cells decreased, while phosphorylated VASP localized to cell-cell junctions and the lengthwise of actin cytoskeleton through confocal microscopy. The expression of phosphorylated VASP and PKC activity also increased in above groups, especially in ox-LDL+PMA group. But the difference between GF109203X and Control group has no statistical significance. These results indicate that the phosphorylation of VASP mediates the changes of cytoskeleton induced by ox-LDL in endothelial cells; PKC is one of the regulated kinases of the phosphorylation of VASP induced by ox-LDL. The research is supported by “ChenGuang Youth Scientific Project of Wuhan” (20015005045).

Papillary muscle approximation combined with ventriculoplasty in patients with ischemic cardiomyopathy and functional mitral regurgitation: effects on mitral valve and LV shape

Recent studies define functional mitral regurgitation (MR) and worsened left ventricular (LV) systolic indices as the widening of the dimension between papillary muscle heads; consequently, narrowing this distance may improve the mitral valve and LV function. Thirty (22 males; mean age: 57+/-7 years) candidates for CABG underwent ventriculoplasty and in 50% of them papillary muscle approximation was also performed (group 1). All the patients had grade 3 to grade 4 MR with an interpapillary muscle distance of more than 2.5 cm. In group 1 the papillary muscles were drawn together by an encircling loop using a 4-mm Gore-Tex tube or umbilical tape. Mitral annuloplasty and Dor procedures were performed in all the patients. Postoperative echocardiography revealed significant changes in systolic and diastolic sphericity indices in the PMA group. There was one hospital death in each group, and within a short mean follow-up period of 9 months, there were no late deaths. Improvement of NYHA class and MR were significantly better in the PMA group. Papillary muscle approximation in selected patients has a clear effect on the mitral valve and LV shape by reducing tethering and sphericity due to the displacement of the papillary muscles.

Polymorphonuclear leukocyte activation induces cerebral hypoperfusion in rats in the absence of previous ischemia-reperfusion damage

We determined if activation of circulating neutrophils could influence local cerebral blood flow (lCBF) and cerebrovascular reactivity without previous ischemic endothelial activation. After intracarotid infusion of phorbol myristate acetate (PMA, twice in 30 min), Laser–Doppler measurements of lCBF in the parietal cortex of anesthetised rats showed a fall of 34% ( P<0.05) at 30 min, but not in the vehicle group nor the group predepleted in polymorphonuclear leukocytes (PMNLs). Blood gases or arterial pressure did not change significantly in any group. The PMNL count fell by 78% at 30 min and reactivity to systemic hypercapnia by 58% at 30–60 min post infusion in the PMA group. These results show that activated PMNLs reduce lCBF and vasoreactivity in the absence of previous cerebral ischemia.

Fecundação e clivagem após a ativação da proteína quinase C durante a maturação de oócitos bovinos

A formação de pró-núcleos, clivagem e perfil protéico foram avaliados após a ativação da proteína quinase C (PQ-C) durante a maturação de complexos cumulus-oócito (CCOs) bovinos. Visando a determinar estes efeitos da PQ-C, 1936 CCOs foram distribuídos aleatoriamente em 4 tratamentos, sendo maturados na presença de PMA (100nM phorbol 12-myristate 13-acetate, ativador da PQ-C), de 4alfa-PDD (100nM de 4alfa-phorbol 12,13-didecanoetate, forbol éster que não ativa a PQ-C; controle forbol éster), de SVE (10% de soro de vaca em estro, controle positivo) e de um controle negativo constituído pelo meio de maturação básico para os demais tratamentos, com exceção do SVE, onde não foi adicionado o álcool polivinílico (PVA). Os CCOs foram mantidos na presença de PMA por 1, 4 e 7 horas, sendo após, transferidos para o meio básico de maturação até que se completassem 24 horas de cultivo. A estimulação da PQ-C, por esses períodos, não alterou a formação de pró-núcleos, porém, diminuiu a percentagem de clivagem dos zigotos. Os resultados do grupo 4alfa-PDD comprovam que as alterações ocorridas no grupo PMA são devido à ativação da PQ-C e não ação direta do forbol éster na célula. A análise da composição protéica demonstrou uma banda de proteína adicional no grupo SVE ao redor de 74 kilo Daltons (kDa). Os resultados desse estudo, quando associados aos dados preliminares de Western blot, indicam a importância da PQ-C na regulação da maturação, fecundação e clivagem de embriões bovinos.

Effects of oleic acid-, alpha-naphthylthiourea-, and phorbol myristate acetate-induced microvascular damage on indexes of pulmonary endothelial function in anesthetized dogs.

To study the value of indexes of endothelial cell function in experimentally induced pulmonary microvascular injury, lung damage was produced in anesthetized dogs by intravenous injection of oleic acid (OA; n = 6), alpha-naphthylthiourea (ANTU; n = 5), or phorbol myristate acetate (PMA; n = 6). Angiotensin-converting enzyme (ACE) activity in serum and simultaneous measurements of serotonin (SER) and propranolol (PROP) pulmonary extraction along with several physiologic parameters were determined and compared with those obtained in a control group (n = 5) before and then at 2-h intervals for 8 h after administration of the toxic agent. ACE activity in serum showed a sustained and significant increase in the PMA and OA groups throughout the whole study period, whereas it decreased significantly at 4 h in the ANTU group. SER pulmonary uptake decreased significantly, but slightly, only in the PMA group at 8 h (-5%). At 6 and 8 h respectively, PROP extraction dropped significantly in the PMA (-11 and -13%) and OA (-13 and -19%) groups. This decrease in PROP extraction was likely to result from physiologic changes due to the development of pulmonary edema as suggested by the correlation between the changes in amine uptake and those affecting pulmonary artery pressure and total static respiratory compliance. The lack of effects on SER uptake by the lungs under these experimental conditions indicate that dissociation exists between metabolic dysfunction of pulmonary endothelial cells and fluid leakage.

The significance of group B streptococci in neonatal pneumonia.

Thirty-eight infants admitted to a neonatal intensive care unit because of pneumonia (14 patients) and pulmonary maladaption syndrome (PMA) (24 patients) were included in the study. Samples of potentially pathogenic, facultatively anaerobic bacteria were taken from the external ear, blood, throat, nasopharynx, umbilicus and gastric aspirates of the children, and from urethra and cervix of the mothers. Group B streptococci (GBS) and Escherichia coli were the only potentially pathogenic bacteria isolated from the infants. Out of 14 infants with pneumonia 11 (79%) harboured one of these bacteria, in contrast to 3 out of 24 (13%) with PMA (P less than 0.001). GBS was found in 8/14 infants with pneumonia and in 1/24 infants with PMA (P less than 0.001). The respective frequencies for Escherichia coli were 3/14 and 2/24 (not significant). The infant and/or the mother in 10/14 pneumonia cases harboured GBS, in contrast to 4/24 pairs in the PMA group (P less than 0.001). The levels of antibodies against GBS in sera of mothers to infants with pneumonia did not differ from the antibody levels in control sera (parturient GBS-carriers giving birth to healthy infants). The results gave evidence for an important manifestation of neonatal GBS-infection: pneumonia without septicemia. The incidence of the disease is estimated to be 1:25 parturient GBS-carriers. Finally, maternal fever, gestational age above 42 weeks, more severe respiratory difficulties and the occurrence of severe changes in fetal heart rate during the first stage of labour were found to be typical characteristics of pneumonia, as compared to PMA.