Carbapenem Derivatives as Potential Inhibitors of Various β-Lactamases, Including Class B Metallo-β-Lactamases

ABSTRACTA variety of 1β-methylcarbapenem derivatives were screened to identify inhibitors of IMP-1 metallo-β-lactamase, a class B β-lactamase, in an automated microassay system using nitrocefin as a substrate. The structure–inhibitory-activity relationship study revealed that three types of 1β-methylcarbapenems having benzothienylthio, dithiocarbamate, or pyrrolidinylthio moieties at the C-2 position showed good inhibitory activity. Among the compounds screened, J-110,441, having a benzothienylthio moiety at the C-2 position of 1β-methylcarbapenem, was the most potent inhibitor of class B metallo-β-lactamases withKivalues of 0.0037, 0.23, 1.00, and 0.83 μM for IMP-1 encoded by theblaIMPgene, CcrA fromBacteroides fragilis, L1 fromStenotrophomonas maltophilia, and type II fromBacillus cereus, respectively. In a further characterization study, J-110,441 also showed inhibitory activity against TEM-type class A serine β-lactamase and chromosomal class C serine β-lactamase fromEnterobacter cloacaewithKivalues of 2.54 and 0.037 μM, respectively. Combining imipenem or ceftazidime with J-110,441 had a synergistic effect on the antimicrobial activity against β-lactamase-producing bacteria. Against the isolates of IMP-1-producingSerratia marcescens, the MICs of imipenem decreased to levels ranging from 1/64 to 1/4 in the presence of one-fourth of the MIC of J-110,441. AgainstE. cloacaeproducing high levels of class C β-lactamase, the MIC of ceftazidime decreased from 64 to 4 μg/ml in the presence of 4 μg of J-110,441 per ml. This is the first report to describe a new class of inhibitor of class B and class C β-lactamases including transferable IMP-1 metallo-β-lactamases.

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Some kinematics of halo coronal mass ejections

Open Astronomy ◽

10.1515/astro-2020-0010 ◽

2020 ◽

Vol 29 (1) ◽

pp. 81-88

Author(s):

Virendra Kumar Verma ◽

Nishant Mittal ◽

Ramesh Chandra

Keyword(s):

Coronal Mass Ejections ◽

Solar Flares ◽

Coronal Holes ◽

Geomagnetic Disturbances ◽

Class A ◽

Heliospheric Physics ◽

Class B ◽

The Mean ◽

Class C

AbstractWe present an investigation of halo coronal mass ejections (HCMEs) kinematics and other facts about the HCMEs. The study of HCMEs is very important because HCMEs are regarded as the main causes of heliospheric and geomagnetic disturbances. In this study, we have investigated 313 HCMEs observed during 1996-2012 by LASCO, coronal holes, and solar flares. We find that HCMEs are of two types: accelerated HCMEs and decelerated HCMEs. The mean space speed of HCMEs is 1283 km/s while the mean speed of decelerated HCMEs and accelerated HCMEs is 1349 km/s and 1174 km/s, respectively. The investigation shows that 1 (0.3%) HCME was associated with class A SXR, 14 (4.7%) HCMEs were associated with class B SXR-flares, 87 (29.4%) HCMEs were associated with class C SXR-flares, 125 (42.2%) HCMEs were associated with class M SXR-flares and 69 (23.3%) HCMEs were associated with class X SXR-flares. The speed of HCMEs increases with the importance of solar SXR-flares. The various results obtained in the present analysis are discussed in the light of the existing scenario of heliospheric physics.

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A 3-tier classification of cerebral arteriovenous malformations

Journal of Neurosurgery ◽

10.3171/2010.8.jns10663 ◽

2011 ◽

Vol 114 (3) ◽

pp. 842-849 ◽

Cited By ~ 164

Author(s):

Robert F. Spetzler ◽

Francisco A. Ponce

Keyword(s):

Surgical Outcomes ◽

Arteriovenous Malformations ◽

Neurological Deficits ◽

Cerebral Arteriovenous Malformations ◽

Pooled Data ◽

Class A ◽

Tier System ◽

Class B ◽

Class C

Object The authors propose a 3-tier classification for cerebral arteriovenous malformations (AVMs). The classification is based on the original 5-tier Spetzler-Martin grading system, and reflects the treatment paradigm for these lesions. The implications of this modification in the literature are explored. Methods Class A combines Grades I and II AVMs, Class B are Grade III AVMs, and Class C combines Grades IV and V AVMs. Recommended management is surgery for Class A AVMs, multimodality treatment for Class B, and observation for Class C, with exceptions to the latter including recurrent hemorrhages and progressive neurological deficits. To evaluate whether combining grades is warranted from the perspective of surgical outcomes, the 3-tier system was applied to 1476 patients from 7 surgical series in which results were stratified according to Spetzler-Martin grades. Results Pairwise comparisons of individual Spetzler-Martin grades in the series analyzed showed the fewest significant differences (p < 0.05) in outcomes between Grades I and II AVMs and between Grades IV and V AVMs. In the pooled data analysis, significant differences in outcomes were found between all grades except IV and V (p = 0.38), and the lowest relative risks were found between Grades I and II (1.066) and between Grades IV and V (1.095). Using the pooled data, the predictive accuracies for surgical outcomes of the 5-tier and 3-tier systems were equivalent (receiver operating characteristic curve area 0.711 and 0.713, respectively). Conclusions Combining Grades I and II AVMs and combining Grades IV and V AVMs is justified in part because the differences in surgical results between these respective pairs are small. The proposed 3-tier classification of AVMs offers simplification of the Spetzler-Martin system, provides a guide to treatment, and is predictive of outcome. The revised classification not only simplifies treatment recommendations; by placing patients into 3 as opposed to 5 groups, statistical power is markedly increased for series comparisons.

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Neuropathologic Examination in Sudden Unexpected Deaths in Infancy and Childhood: Recommendations for Highest Diagnostic Yield and Cost-Effectiveness in Forensic Settings

Academic Forensic Pathology ◽

10.23907/2017.020 ◽

2017 ◽

Vol 7 (2) ◽

pp. 182-199 ◽

Cited By ~ 3

Author(s):

Rebecca D. Folkerth ◽

Jacqueline Nunez ◽

Zhanna Georgievskaya ◽

Declan McGuone

Keyword(s):

Diagnostic Yield ◽

Sinus Thrombosis ◽

Age Determination ◽

Febrile Seizures ◽

Manner Of Death ◽

Final Cause ◽

Class A ◽

Class B ◽

Class C ◽

Walker Malformation

In infants and toddlers (less than four years of age), determination of cause and manner of death often requires a complete autopsy. Few evidence-based guidelines exist regarding optimum nervous system sectioning in this population. Over a six-month interval and using a comprehensive section protocol, we categorized cases having neuropathological findings that were critical (Class A), contributory (Class B), or noncontributory (Class C) to the final cause and manner of death. We further evaluated which sections helped make this determination. Among 53 cases (44 infants, 9 toddlers; 26 girls, 27 boys), Class A neuropathology was noted in nine (16.9%). Seven infants had meningoencephalitis (2/7, 28.6%), craniospinal trauma (3/7, 42.8%), brainstem necrosis suggesting Leigh Disease (1/7, 14.3%), and hydrocephalus in Dandy-Walker malformation (1/7, 14.3%); two toddlers had inflicted craniospinal trauma (2/2, 100%). Class B factors were identified in 11/53 (20.8%), including recent hypoxic-ischemic lesions (2/11, 18.2%), meningitis or dural venous sinus thrombosis in systemic sepsis (2/11, 18.2%), multicystic encephalopathy following peripartum asphyxia (2/11, 18.2%), and microcephaly and delayed myelination (Cri-du-Chat Syndrome) (1/11, 9.09%). Class B also included three toddlers (3/11, 27.2%) with features of hippocampal dysgenesis, two in the setting of febrile seizures. Class C comprised normal brains (3/53, 5.7%), and those with findings of uncertain significance, such as white matter and brainstem gliosis (30/53, 56.6%). The sections most valuable for detection of relevant pathology, and thus recommended for routine sampling, were: 1) bilateral hippocampus; 2) cerebral cortex and leptomeninges; and 3) pons or medulla.

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Correlation between Genotypic Diversity, Lipooligosaccharide Gene Locus Class Variation, and Caco-2 Cell Invasion Potential of Campylobacter jejuni Isolates from Chicken Meat and Humans: Contribution to Virulotyping

Applied and Environmental Microbiology ◽

10.1128/aem.02269-08 ◽

2009 ◽

Vol 75 (13) ◽

pp. 4277-4288 ◽

Cited By ~ 48

Author(s):

Ihab Habib ◽

Rogier Louwen ◽

Mieke Uyttendaele ◽

Kurt Houf ◽

Olivier Vandenberg ◽

...

Keyword(s):

Campylobacter Jejuni ◽

Genotypic Diversity ◽

Chicken Meat ◽

Pcr Screening ◽

Class A ◽

Invasion Potential ◽

Cell Surface Carbohydrate ◽

Significant Difference ◽

Class B ◽

Class C

ABSTRACT Significant interest in studying the lipooligosaccharide (LOS) of Campylobacter jejuni has stemmed from its potential role in postinfection paralytic disorders. In this study we present the results of PCR screening of five LOS locus classes (A, B, C, D, and E) for a collection of 116 C. jejuni isolates from chicken meat (n = 76) and sporadic human cases of diarrhea (n = 40). We correlated LOS classes with clonal complexes (CC) assigned by multilocus sequence typing (MLST). Finally, we evaluated the invasion potential of a panel of 52 of these C. jejuni isolates for Caco-2 cells. PCR screening showed that 87.1% (101/116) of isolates could be assigned to LOS class A, B, C, D, or E. Concordance between LOS classes and certain MLST CC was revealed. The majority (85.7% [24/28]) of C. jejuni isolates grouped in CC-21 were shown to express LOS locus class C. The invasion potential of C. jejuni isolates possessing sialylated LOS (n = 29; classes A, B, and C) for Caco-2 cells was significantly higher (P < 0.0001) than that of C. jejuni isolates with nonsialylated LOS (n = 23; classes D and E). There was no significant difference in invasiveness between chicken meat and human isolates. However, C. jejuni isolates assigned to CC-206 (correlated with LOS class B) or CC-21 (correlated with LOS class C) showed statistically significantly higher levels of invasion than isolates from other CC. Correlation between LOS classes and CC was further confirmed by pulsed-field gel electrophoresis. The present study reveals a correlation between genotypic diversity and LOS locus classes of C. jejuni. We showed that simple PCR screening for C. jejuni LOS classes could reliably predict certain MLST CC and add to the interpretation of molecular-typing results. Our study corroborates that sialylation of LOS is advantageous for C. jejuni fitness and virulence in different hosts. The modulation of cell surface carbohydrate structure could enhance the ability of C. jejuni to adapt to or survive in a host.

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Cardiomyopathy in Cirrhotic Patients and Its Relationship with the Severity of Cirrhosis

10.53350/pjmhs2115102779 ◽

2021 ◽

Vol 15 (10) ◽

pp. 2779-2782

Author(s):

Saira Khalid ◽

Nasir Shah ◽

Yasir Abbas Zaidi ◽

Muhammad Saleem Hasan ◽

Saqib Jahangir ◽

...

Keyword(s):

Liver Cirrhosis ◽

Severe Disease ◽

P Value ◽

Cirrhotic Cardiomyopathy ◽

Male Predominance ◽

Class A ◽

Class B ◽

Cirrhotic Patients ◽

The Mean ◽

Class C

Study Objectives: To determine the frequency of cirrhotic cardiomyopathy in patients with liver cirrhosis and to compare it across varying grades of cirrhosis on Child Turcotte Pugh classification. Study Design and Settings: It was a descriptive cross-sectional study carried at Department of Medicine, Lahore General Hospital Lahore over 1 year from Jan 2018 to Dec 2018. Patients and Methods: The present research involved 100 male and female patients aged between 16-70 years having liver cirrhosis diagnosed at least 6 months ago. These patients underwent echocardiographic screening of cardiomyopathy which was diagnosed by the presence of diastolic dysfunction (i.e. increased E/A ratio>1). An informed written consent was obtained from every patient. Results of the Study: There was a male predominance (M:F, 1.6:1) among cirrhotic patients with a mean age of 51.9±9.8 years. The mean BMI was 26.5±3.7 Kg/m2 while the mean duration of cirrhosis was 22.0±10.9 months. Majority (49.0%) of the patients belonged to CTP Class C followed by Class-B (39.0%) and Class-A (12.0%). Cirrhotic cardiomyopathy was observed in 41.0% patients with cirrhosis. There was statistically insignificant difference in the observed frequency of cirrhotic cardiomyopathy among various subgroups of cirrhotic patients depending upon patient’s age (p-value=0.928), gender (p-value=0.997), BMI (p-value=0.983) and duration of disease (p-value=0.782). However, it increased considerably with worsening of disease on CTP Classification; Class-A vs. Class-B vs. Class-C (8.3% vs. 35.9% vs. 53.1%; p-value=0.013). Conclusion: Cirrhotic cardiomyopathy was observed in a substantial proportion of cirrhotic patients and was more frequent in patients with more severe disease which warrants routine echocardiographic screening of cirrhotic patients so that timely recognition and anticipated treatment of this complication may improve the case outcome in future medical practice. Keywords: Cirrhosis, Cardiomyopathy, Child Turcotte Pugh Class

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Intrinsic features contributing to spike train patterning in proprioceptive cuneate neurons

Journal of Neurophysiology ◽

10.1152/jn.1987.57.4.962 ◽

1987 ◽

Vol 57 (4) ◽

pp. 962-976 ◽

Cited By ~ 4

Author(s):

D. J. Surmeier ◽

A. L. Towe

Keyword(s):

Computer Simulation ◽

Spike Train ◽

Spike Trains ◽

Antidromic Activation ◽

Synaptic Potentials ◽

Class A ◽

Class B ◽

Class C ◽

Discharge Patterns ◽

Periodic Inputs

The intrinsic processes contributing to the three discharge patterns of proprioceptive cuneate neurons described by Surmeier and Towe were studied experimentally and with computer simulation. Examination of the alterations in excitability produced by antidromic activation suggested that a prolonged inhibition was a concomitant of discharge in proprioceptive cuneate neurons. Computer simulation was performed to test the possible roles of inhibitory hyperpolarizing processes in governing the observed discharge patterns. These simulations used two constant threshold models. The simplest model linearly integrated synaptic potentials until the spike threshold was reached. After the discharge, synaptic potentials that preceded the spike were ignored (i.e., the model was "reset"). The second model was similar to the first except that following a spike two hyperpolarizing processes were activated and preceding events continued to play a role in membrane potential. Simulation of class A spike trains that possessed positive correlations between nearby intervals was successful only with a resetting model. This suggested that class A neurons have fast, no-memory postspike conductance changes, which effectively shunt synaptic charge. Simulation of class B spike trains was possible with the nonresetting model. At least two periodic inputs, which evoked brief, relatively large EPSPs, were required. In addition, a prominent, fast, spike-dependent hyperpolarization and a small-amplitude, slow hyperpolarization were required. Simulation of class C spike trains was also possible with the nonresetting model. Several periodic inputs were required; one input had to evoke a slow suprathreshold EPSP. In contrast to class B simulations, class C spike train simulation required that a large-amplitude, slow hyperpolarization, as well as a brief hyperpolarization, following spike initiation. The results of class B and C simulations suggested that these two groups differed primarily in the amplitude of a slow, hyperpolarizing, postspike conductance. Some role may also be played by the time course of the driving EPSPs.

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Interactions of Ceftobiprole with β-Lactamases from Molecular Classes A to D

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00218-07 ◽

2007 ◽

Vol 51 (9) ◽

pp. 3089-3095 ◽

Cited By ~ 59

Author(s):

Anne Marie Queenan ◽

Wenchi Shang ◽

Malgosia Kania ◽

Malcolm G. P. Page ◽

Karen Bush

Keyword(s):

Functional Groups ◽

Hydrolytic Stability ◽

Enterobacter Cloacae ◽

Class A ◽

Extended Spectrum ◽

Class D ◽

The Family ◽

Class B ◽

The Common ◽

Antibacterial Spectrum

ABSTRACT The interactions of ceftobiprole with purified β-lactamases from molecular classes A, B, C, and D were determined and compared with those of benzylpenicillin, cephaloridine, cefepime, and ceftazidime. Enzymes were selected from functional groups 1, 2a, 2b, 2be, 2d, 2e, and 3 to represent β-lactamases from organisms within the antibacterial spectrum of ceftobiprole. Ceftobiprole was refractory to hydrolysis by the common staphylococcal PC1 β-lactamase, the class A TEM-1 β-lactamase, and the class C AmpC β-lactamase but was labile to hydrolysis by class B, class D, and class A extended-spectrum β-lactamases. Cefepime and ceftazidime followed similar patterns. In most cases, the hydrolytic stability of a substrate correlated with the MIC for the producing organism. Ceftobiprole and cefepime generally had lower MICs than ceftazidime for AmpC-producing organisms, particularly AmpC-overexpressing Enterobacter cloacae organisms. However, all three cephalosporins were hydrolyzed very slowly by AmpC cephalosporinases, suggesting that factors other than β-lactamase stability contribute to lower ceftobiprole and cefepime MICs against many members of the family Enterobacteriaceae.

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THE RELATIONSHIP BETWEEN ENDOSPERM DEVELOPMENT AND MORPHOLOGIC CHARACTERS IN THE F2 GENERATION OF A T. DICOCCUM × T. VULGARE CROSS

Canadian Journal of Research ◽

10.1139/cjr31-064 ◽

1931 ◽

Vol 5 (2) ◽

pp. 208-218 ◽

Cited By ~ 1

Author(s):

J. B. Harrington

Keyword(s):

Random Sample ◽

Large Population ◽

Morphological Characters ◽

Endosperm Development ◽

Class A ◽

Class B ◽

Class C ◽

F2 Generation ◽

The Individual ◽

The Relationship

The relationship between the degree of plumpness of F2 seeds and the type of the resulting F2 plants was studied in the cross Vernal (T. dicoccum) × Marquis (T. vulgare). A random sample of F2 seeds was divided into three classes based upon kernel plumpness, viz. plump (Class A), slightly shrunken (Class B), and shrunken (Class C). In these there were by number 55.5, 41.0 and 3.5% of seeds respectively. Emergence of F2 plants in the field was 64, 58 and 36% for Classes A, B and C. The F2 plants were studied for 13 morphological characters. Comparing the populations for all characters combined, Class A was more dicoccum-like than Class B, and Class B much more dicoccum-like than Class C. The proportion of vulgare-like character was 16, 20 and 32% for Classes A, B and C, respectively. Considering the character of the individual plants, the ratios of dicoccum-like to vulgare-like were 12.1:1, 5.3:1, and 2.2:1 for classes A, B and C, respectively. Furthermore, the vulgare-like plants of classes A and B were less vulgare-like than those of Class C. There were present, however, in Classes A and B some plants that were fully as vulgare-like as any in Class C. These results indicate that, in an interspecific wheat cross, the breeder should give special attention to the shrunken F2 seeds if he has very limited nursery space and a large amount of seed; whereas if he has plenty of space for a large population, special care of shrunken F2 seeds does not seem warranted.

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Review of the Toxicology of Mineral Spirits

International Journal of Toxicology ◽

10.1080/10915810701876786 ◽

2008 ◽

Vol 27 (1) ◽

pp. 97-165 ◽

Cited By ~ 17

Author(s):

Marie A. Amoruso ◽

John F. Gamble ◽

Richard H. McKee ◽

Arlean M. Rohde ◽

Andrew Jaques

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Acute Toxicity ◽

Systemic Effects ◽

Type I ◽

Type Ii ◽

Class A ◽

Boiling Range ◽

Class C ◽

Mineral Spirits

This review of the toxicology of mineral spirits covers studies of the major classes of mineral spirits and several toxicologically important mineral spirit constituents. This review cites data from numerous previously unpublished animal toxicology studies conducted on mineral spirits during the past 30 years, expanding the existing database on the toxicology of this group of hydrocarbon solvents. The data can be used to better evaluate the potential effects associated with exposure to these materials, including health and environmental reviews such as the U.S. Environmental Protection Agency High Production Volume (HPV) chemical program and the Organization for Economic Cooperation and Development (OECD) HPV Screening Information Data Set (SIDS) program. The majority of animal toxicology studies in the available literature were conducted on mineral spirits categorized as ASTM D235 Type I Class A (149°C to 213°C boiling range; 8% to 22% aromatics) and demonstrate that Type I Class A mineral spirits have a low order of acute toxicity and do not produce significant systemic effects. Some additional studies conducted with ASTM D235 Type II Class C mineral spirits (177°C to 213°C boiling range; <2% aromatics) suggest that Type II Class C mineral spirits have similar toxicity to Type I Class A mineral spirits, though there is some evidence that Type II, Class C mineral spirits have a lesser degree of central nervous system (CNS) effects than the higher aromatic containing Type I Class A materials. In addition, toxicity data on selected chemical constituents of mineral spirits (e.g., n-nonane, n-decane, n-undecane) indicate that these chemicals have similar toxicological properties to mineral spirits. Overall, the data showed that mineral spirits have a low order of acute toxicity and do not appear to produce toxicologically relevant systemic effects. Ongoing studies are evaluating the concerns associated with chronic low-level exposure and central nervous system effects.

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Correlation between Hepatic Vein Wave form Changes on Doppler Ultrasound and the Severity of Diseases in Cirrhotic Patients

Journal of Medicine ◽

10.3329/jom.v22i2.56698 ◽

2021 ◽

Vol 22 (2) ◽

pp. 100-106

Author(s):

Tarana Yasmin ◽

Sohely Sultana ◽

Mahmuda Nusrat Ima ◽

Md Quamrul Islam ◽

Shyamal Kumar Roy ◽

...

Keyword(s):

Liver Cirrhosis ◽

Doppler Ultrasound ◽

Hepatic Vein ◽

Wave Form ◽

Venous Blood Flow ◽

Class A ◽

Class B ◽

Pugh Class ◽

Cirrhotic Patients ◽

Class C

Background: Cirrhosis is a common problem and is a leading cause of chronic liver disease. Early diagnosis with assessment of severity of diseases may help prevent the associated complications and patients’ sufferings. Now a days Hepatic venous Doppler can be a tool for diagnosis of cirrhosis and to assess correlation between waveform changes and severity of diseases. Objective: The purposes of this study was to determine the significance of hepatic vein waveform changes on doppler ultrasound in cirrhotic patients and to correlate with liver dysfunction. Materials and methods: This study was carried out in the department of Radiology and Imaging of Enam Medical College and Hospital during January 2017 to May 2018. Doppler waveforms were obtained from right hepatic vein in all the cases and classified as triphasic, biphasic and monophasic. Waveform comparisons were made among patients with differing grades of cirrhosis. Child- Pugh class was used to assess severity of cirrhosis. Doppler sonography was done in 80 patients suspecting of having liver cirrhosis. Data on clinical findings, B mode sonographic findings and hepatic vein doppler ultrasound findings were collected and documented in structured forms. Analysis was done using SPSS - 20. Results: Total of 80 patients who met the inclusion criteria are included in the study with mean age of 45.37±7.64 (range 25-75) years. Among these 57 (71%) were males while 23(29%) were females. On the basis of hepatic function 25 (31%) patients presented in Child-Pugh Class A, 31(39%) with Class B and 24(30%) patients had Class C. Hepatic venous waveform was triphasic in 22 (27.5%), biphasic in 28(35%), and monophasic in 30 (37.5%) cases. Our study revealed 88% (21) of Child- Pugh Class C, 23% (7) of Class B and 8% (2) of class A patients had monophasic HV waveform. The hepatic venous waveform progressively changed from triphasic to biphasic to monophasic with advancing grade of cirrhosis. The relationship of these waveforms change had significant relation with hepatic dysfunction (p < 0.022). Conclusion: Hepatic vein wave form changes reflects the change in hepatic circulation associated with progression of liver cirrhosis. It can be used as a new parameter in the assessment of severity of liver cirrhosis. Thus, alteration in hepatic venous blood flow pattern on doppler ultrasound can be a useful noninvasive tool for evaluating diseases severity in patients with cirrhosis. J MEDICINE 2021; 22: 100-106

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