Liquor Bilirubin Levels in Normal Pregnancy: A Reassessment of Early Prediction of Haemolytic Disease

A comparison was made between chemically and spectrophotometrically determined concentrations of total bile pigment in the liquor amnii. For the period 16 to 26 weeks'' gestation the upper limit of normal bile pigment to protein ratio was found to be 0·4. Levels above this would be required as an indication for intrauterine transfusion. In 110 cases of isoimmunization of pregnancy these criteria were applied in the diagnosis of severity of the condition. The ratio of the bile pigment to protein was used rather than a simple bile pigment measurement, and found to be valuable.Nevertheless, it is important to emphasize that fallacious high bilirubin readings may arise by using whatever method, particularly owing to bilirubin and other breakdown products of blood contaminating the liquor.     

Liquor Bilirubin Levels and False Prediction of Severity in Rhesus Haemolytic Disease

Liquor bilirubin levels gave a false prediction of outcome for the fetus in 80 out of 716 rhesus-sensitized women referred for treatment during 1965-9. Trauma caused by amniocentesis seemed to be responsible for an increase in the severity of immunization in a significant proportion of cases. In addition, contamination of liquor samples by plasma, particularly fetal plasma, completely invalidated liquor bilirubin estimations. Errors in estimation of gestational length were also found to be associated with misleading results and a poor fetal prognosis.     

Selenium levels in men with liver disease in Hungary

ProjectWe studied the relationship between selenium (Se) levels and chronic liver disease (CLD) severity and the association between socioeconomic and lifestyle factors and serum Se levels.ProcedureWe performed a case–control study in Hungarian men, examining 281 patients with CLD and 778 controls. Liver function was evaluated using biochemical markers, and liver disease was verified with physical examination and blood tests. Linear regression analysis was performed to study the association of serum Se level with biochemical markers in cases and controls. In control participants we examined the relationship between Se levels and age, financial status, education, alcohol consumption, cigarette smoking, type of fat used for cooking and body mass index.ResultsSerum Se levels were lower in cases (median 0.87 μmol/L (IQR: 0.77–1.03)) than in controls (median 1.08 μmol/L (IQR: 0.97–1.19)). In controls, increases in bilirubin and glutamic-oxaloacetic transaminase (GOT) were associated with decreases in Se levels. In patients with CLD, a statistically significant relationship was found between serum Se and the GOT/GPT ratio, albumin and bilirubin. Younger, better-educated controls had significantly higher, and regular smokers and heavy drinkers had significantly lower Se levels. The use of vegetable oil/fat was also associated with higher Se levels. Se level was associated with the severity of liver injury in people even in patients who did not exhibit signs and symptoms of CLD.ConclusionsSerum Se level is strongly associated with the severity of liver damage in people with CLD from the early stage on.     

Biochemical predictors for Sars-Cov-2 severity

It is of interest to assess the inflammatory marker profile in SARS-CoV-2 patients and to correlate the levels of systemic inflammatory biomarkers such as neutrophil-to-lymphocyte ratio (NLR), C-Reactive Protein CRP, Ferritin, Creatine kinase (CK), Lactate dehydrogenase (LDH) and liver function analytes total serum proteins, albumin, total bilirubin, direct bilirubin, alkaline phosphatase, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) with the severity of SARS-CoV-2 infections. A total of 1000 COVID-19 positive patient''s data were collected. Laboratory assessments consisted of NLR (neutrophil-lymphocyte ratio) by cell counter, C Reactive Protein (CRP) by immunoturbidimetry, Ferritin by electrochemiluminescence (ECLIA) and Creatine Kinase (CK), Lactate Dehydrogenase (LDH), Alkaline phosphatase (ALP), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Total Bilirubin, Direct Bilirubin, Total Protein and Albumin by spectrophotometry. The mean plasma CRP levels, NLR, ferritin, CK and LDH levels were higher in severe cases than in non-severe cases, and the difference was statistically significant (p<0.05). All liver function tests such as the total and direct bilirubin, AST, ALT, ALP, total protein and albumin were higher in severe patients than non-severe patients and the difference was statistically significant (p<0.05). Data indicate that NLR, CRP, Ferritin, CK, LDH and liver function analytes have a crucial role as prognostic markers for SARS-CoV-2 infections and hence should be routinely recommended for risk assessment and stratification of the patients to reduce the associated morbidity and mortality.     

血清胆红素水平与缺血性卒中的相关性研究

目的：脑卒中是威胁人类健康三大疾病之一,是我国成人致残的首要原因,其中80％是缺血性卒中。本文意在研究血清胆红素水平与缺血性卒中严重程度、发病机理以及颈动脉粥样硬化斑块的关系,以进一步为防治缺血性卒中的发生、发展提供新的途径。方法：选择缺血性脑卒中患者（观察组）150例和同期健康体检者（对照组）150例,分别测定两组的血清总胆红素水平（TBIL）、间接胆红素（DBIL）、直接胆红素（IBIL）,并对病例组进行TOAST分型、NIHSS评分及颈部血管超声检查。比较两组间血清胆红素,及观察组内不同分型组间血清胆红素的差异。结果：缺血性卒中患者TBIL、DBIL水平显著高于正常对照组,差异具有统计学意义（P〈0．05）。缺血性卒中患者按TOAST分型各亚型间血清TBIL、DBIL、IBIL水平差异无统计学意义（P〉0．05）。中重型脑梗死组与轻型脑梗死组比较,血清TBIL、DBIL、IBIL浓度均明显升高,差别具有统计学意义（P〈0．05）。缺血性卒中患者中有动脉粥样硬化斑块形成组血清TBIL、DBIL水平低于颈部动脉内膜光滑、完整者组,差别有统计学意义（P〉0．05）。结论：缺血性卒中患者血清胆红素升高,参与急性应激反应,可能作为衡量缺血性卒中严重程度的指标之一;高水平血清胆红素可能预防颈动脉粥样硬化斑块的形成,从而预防缺血性卒中的发生。     

溶血反应对临床生化检验结果的影响分析

目的:研究分析溶血反应对临床生化检测结果的影响。方法:收集我院2015年1月至12月120例正常人体检血液标本资料,采用控制变量法,在试管1中放入正常血液,试管2中放入发生溶血反应血液,分别检测两组血液临床生化指标,并比对变化数据。结果:在检测的17项数据中,血糖、总胆红素、直接胆红素、谷草转氨酶、谷丙转氨酶、碱性磷酸酶、总蛋白、甘油三酯、尿酸、总胆固醇、乳酸脱氢酶等11项数据在试管1与试管2中,检测指标变化大,具有统计学意义(P0.05)。白蛋白、肌酐、尿酸氮、血钙、酸性磷酸酶、血磷等六项指标在试管1与试管2中,含量检测基本无变化(P0.05)。结论:溶血反应的发生对临床生化检测结果影响很大,发生溶血反应会直接影响到酶类等指标的检测结果的准确性,临床检测中应尽量避免溶血反应。     

下肢动脉硬化闭塞症患者血清胆红素含量的分析

目的：分析血清胆红素与动脉硬化闭塞症的相关性及临床意义。方法：1）回顾性分析我院2011年1月至2012年11月,318例符合下肢动脉硬化闭塞症诊断者的血清胆红素含量。并依照Fontaine分类法将患者分成临床四期。2）回顾性分析我院体检中心2012年100例体检者的血清胆红素含量。3）将上述1、2组的数据做两样本t检验,并将1组数据根据临床的分级进行内部小组t检验。以P〈0．05为有差异,P〈0．01为有显著差异。结果：动脉硬化闭塞症的患者血清总胆红素、直接胆红素、间接胆红素的含量均明显低于正常对照组,且动脉硬化闭塞症患者随着临床分级的进展而进一步降低。结论：动脉硬化闭塞症患者的血清胆红素水平与其发生成负性相关,低浓度血清胆红素是独立的动脉硬化闭塞症的危险因素。     

Bilirubin and the risk of common non-hepatic diseases

Bilirubin is a potent antioxidant but can be toxic at high concentrations. This article critically reviews the reported relationships of plasma bilirubin levels to the severity and/or incidence of various common non-hepatic diseases. Plasma bilirubin levels are reportedly negatively related to the risk of atherosclerotic diseases, cancers, demyelinating neuropathies and seasonal affective disorder. By contrast, the incidence and severity of schizophrenia are increased by elevated bilirubin levels. The data strongly suggest that the level of plasma bilirubin should be considered as a risk factor for several common non-hepatic diseases. Additional studies are needed to clarify the mechanisms of this influence, which are thought to be related to unconjugated bilirubin counteracting the oxidative stress underlying these disorders.     

Plasma levels of soluble ST2, but not IL‐33, correlate with the severity of alcoholic liver disease

Alcoholic liver disease (ALD) is a complication that is a burden on global health and economy. Interleukin‐33 (IL‐33) is a newly identified member of the IL‐1 cytokine family and is released as an “alarmin” during inflammation. Soluble suppression of tumourigenicity 2 (sST2), an IL‐33 decoy receptor, has been reported as a new biomarker for the severity of systemic and highly inflammatory diseases. Here, we found the levels of plasma sST2, increased with the disease severity from mild to severe ALD. Importantly, the plasma sST2 levels in ALD patients not only correlated with scores for prognostic models (Maddrey's discriminant function, model for end‐stage liver disease and Child‐Pugh scores) and indexes for liver function (total bilirubin, international normalized ratio, albumin, and cholinesterase) but also correlated with neutrophil‐associated factors as well as some proinflammatory cytokines. In vitro, lipopolysaccharide‐activated monocytes down‐regulated transmembrane ST2 receptor but up‐regulated sST2 mRNA and protein expression and produced higher levels of tumour necrosis factor‐α (TNF‐α). By contrast, monocytes pretreated with recombinant sST2 showed decreased TNF‐α production. In addition, although plasma IL‐33 levels were comparable between healthy controls and ALD patients, we found the IL‐33 expression in liver tissues from ALD patients was down‐regulated at both RNA and protein levels. Immunohistochemical staining further showed that the decreased of IL‐33‐positive cells were mainly located in liver lobule area. These results suggested that sST2, but not IL‐33, is closely related to the severity of ALD. Consequently, sST2 could be used as a potential biomarker for predicting the prognosis of ALD.     

用siRNA沉默人血红素加氧酶-1基因降低胆红素水平

拟通过RNA干扰技术特异下调人血红素加氧酶-1(human heme oxygenase-1,hHO-1)基因的表达,减少hHO-1的产量从而降低胆红素的产生,探讨在胆红素产生前就阻断其产生,为临床早期防治新生儿高胆红素血症及胆红素中毒性脑病探索一种新的有效手段。针对hHO-1基因设计并化学合成三对小分子干扰RNA(small interfering RNA,siRNA)。采用脂质体转染法将siRNA转染入人肝脏细胞株HL-7702;荧光显微镜检测siRNA转染细胞的效率;转染siRNA1~2天后经RT-PCR和Western印迹方法检测hHO-1表达水平和蛋白质量;并采用HO-1诱导剂血红素诱导或hHO-1表达质粒转染细胞以上调hHO-1表达,检测siRNA干扰后hHO-1产量和酶活性。结果显示:设计的三对siRNA能不同程度的特异下调hHO-1表达,筛选获得抑制效果最佳的siRNA-3。siRNA-3抑制hHO-1呈现浓度与时间依赖性。与非特异对照siRNA及未处理组比较,血红素诱导和hHO-1表达质粒转染均能上调HL-7702细胞内hHO-1表达,提高hHO-1产量,但转染siRNA-3后hHO-1表达明显抑制,同时hHO-1活性随着基因表达下调而下降。实验表明设计合成的siRNA-3抑制效果明显。siRNA-3通过降解hHO-1,减少hHO-1产量,降低酶活性,最终减少胆红素产生,从而使RNA干扰技术成为降低新生儿高胆红素血症和胆红素中毒性脑病发生的一种候选方法。     

Strip counts as a means of determining densities and habitat utilization patterns in lake fishes

Synopsis The strip count method of determining fish densities was investigated for a small lake in a series of inshore sites that differed in their physical and biological characteristics and in the communities of fishes present. Overall total numbers of fish, number of species, ratio of commonest to total species, and 2nd commonest to total species, were investigated. Counts were made during time of the feeding peaks.Repeatability of the method was tested by series of five traverses at 10-minute intervals and was good both for total numbers of fish and ratio of commonest species to total fish. However, it varied with the habitat type, being excellent for small semi-isolated weedy sites, good for gravel-bottom sites, but only fair in open sandy bays where the strip was laid in the middle of an extensive area of homogeneous habitat.Series of comparative counts made (a) between morning and afternoon on the same day and, (b) between successive mornings, to determine how constant populations were between these time intervals, proved to be within the same general range but were significantly different by the Mann Whitney U test at the = 0.05 level.In small lakes the strip count method proves to have considerable potential in the study of habitat specializations, taxocene structures, and relative abundances.     

不同剂量阿托伐他汀钙短期应用对冠状动脉粥样硬化性心脏病患者血清 胆红素水平的影响

目的:探讨不同剂量阿托伐他汀钙短期应用对冠状动脉粥样硬化性心脏病患者血清胆红素水平的影响。方法:按照详细的纳入及排除标准的筛选共计264例冠状动脉粥样硬化性心脏病患者入选,分为20 mg和40 mg治疗剂量组,观察患者用药前后胆红素水平的变化水平的改变。结果:与服药前的相比,服用阿托伐他汀钙40 mg和20 mg的患者血清总胆红素、直接胆红素水平均呈显著性上升(P0.05),而间接胆红素水平差异无显著性。服药1个月后,40 mg组患者血清总胆红素、直接胆红素水平升高较20 mg组更显著(P0.05),但两组间接胆红素水平差异没有显著性。总胆红素变化率与患者胆固醇水平呈显著相关性,其20mg组为0.419,40 mg组为0.634(P0.001)。结论:阿托伐他汀钙治疗冠状动脉粥样硬化性心脏病患者可导致其血清总胆红素和直接胆红素水平升高,且高剂量较低剂量对总胆红素和直接胆红素的影响更明显。     

Relationship between Serum Bilirubin and Left Ventricular Hypertrophy in Patients with Essential Hypertension

Background

Prospective studies have found low bilirubin levels were an important predictive factor of cardiovascular events. However, few have yet investigated possible association between serum bilirubin level and LVH in essential hypertension. The aim of the present study was to evaluate the relationship between serum bilirubin levels with LVH in newly diagnosed hypertension patients.

Methods

The present study evaluated the relationship between serum total bilirubin level and left ventricle hypertrophy (LVH) in newly diagnosed hypertensive patients with a sample size of 344. We divided subjects into LVH group (n=138) and non-LVH group (n=206). Physical examination, laboratory tests and echocardiography were conducted. The multivariate logistic regression model was used to verify the independent association between RDW and LVH.

Results

Our results found that patients with LVH had lower bilirubin levels than non-LVH ones. Stepwise multiple linear regression analysis showed total bilirubin level (B=-0.017, P=0.008) was negatively associated with left ventricle mass index (LVMI) even adjusting for some confounders. The multiples logistic regression found total bilirubin level was independently related with of LVH, as a protective factors (OR=0.91, P=0.010).

Conclusion

As a routine and quick laboratory examination index, serum bilirubin may be treated as novel marker for evaluating LVH risk in hypertensive patients. Cohort study with larger sample size are needed.     

Prediction of Severe Neonatal Hyperbilirubinemia Using Cord Blood Hydrogen Peroxide: A Prospective Study

Background

We hypothesized that cord blood hydrogen peroxide (H₂O₂) could be utilized to predict the severity of neonatal hyperbilirubinemia.

Methods

We prospectively enrolled term or near-term healthy neonates. Cord blood and capillary blood at three days of age were measured for hydrogen peroxide and bilirubin concentrations. For newborns with hyperbilirubinemia, further blood samples were obtained at five and seven days of age. Newborns were divided into severe or less severe hyperbilirubinemic groups (peak bilirubin ≥17 mg/dL or not). The sensitivity, specificity, and negative predictive values were determined.

Results

There were 158 neonates enrolled. The incidence of neonatal hyperbilirubinemia was 30.5% for a concentration ≥15 mg/dl. The rising patterns were similar among bilirubin concentrations and hydrogen peroxide levels during the first few days of life. There was a strong positive correlation between bilirubin concentrations and hydrogen peroxide levels after correlation analysis. The rate of severe hyperbilirubinemia was 13.3%. It revealed that a cord blood hydrogen peroxide signal level of 2500 counts/10 seconds was an appropriate cut-off for predicting severe hyperbilirubinemia. Sensitivity and the negative predictive value were 76.2% and 93.3%, respectively.

Conclusions

Our findings confirm that hydrogen peroxide levels and bilirubin concentrations in cord and neonatal blood are closely related. A cord blood hydrogen peroxide level above 2500 counts/10 seconds associated with a high predictive value for severe hyperbilirubinemia. This method provides information about which neonate should be closely followed after discharge from the nursery.     

Inverse relationship between serum bilirubin and atherosclerosis in men: a meta-analysis of published studies

Bilirubin, a major intravascular product of heme catabolism, is a potent antioxidant compound. Numerous studies have been published showing the relationship between serum bilirubin levels and atherosclerosis. In the present investigation all the epidemiological studies available on the effect of serum bilirubin levels and atherosclerotic disease were analyzed. Studies on the epidemiology of atherosclerotic diseases in relation to serum bilirubin levels were searched in the MEDLINE database. Selected studies were subdivided according to serum bilirubin levels and severity of atherosclerotic disease. Because of the limited number of females involved in the studies, only males were included into meta-analysis. Associations for ordered categorical variables (bilirubin and natural history of graded atherosclerosis) were assessed to find correlation and linear trend between analyzed variables. A stratified analysis was conducted to compare risks of clinical outcomes. Eleven relevant studies were used for analysis. A close negative relationship was found between serum bilirubin levels and severity of atherosclerosis (Spearman rank coefficient r = -0.31,P < 0.0001). The linear trend was confirmed in analysis of proportions with x(2) values for both disease conditions to be very significant (P < 0.0001). Unambiguous inverse relationship between serum bilirubin levels and atherosclerosis was demonstrated in this preliminary meta-analytic study. These results indicate the importance of hem oxygenase-related products in the prevention of oxidative stress-mediated diseases.     

Atomic force microscopy of the erythrocyte membrane in obstructive jaundice

The erythrocyte intracellular pressure was calculated using a biomechanical model of the erythrocyte and atomic-force-microscopy (AFM) data. The intracellular pressure was characterized as a function of the model erythrocyte morphology. Based on numerical modeling and data of erythrocyte imaging by AFM, a method was developed to estimate the erythrocyte intracellular pressure by comparing experimental data and the results of numerical calculations. Calculations were performed for erythrocytes of dwarf domestic pigs with and without obstructive jaundice that varied in severity. The erythrocyte membrane was affected with increasing disease severity and blood bilirubin concentration, i.e., the erythrocyte volume increased on average, and substantial changes were observed for erythrocyte intracellular pressure relative to its normal value. As an example, an increase in bilirubin concentration from 5 to 96 μmol/L was associated with an increase in intracellular pressure from 0 to 2.2 kPa. An examination of the erythrocyte membrane surface by high-resolution AMF showed that the membrane is disrupted with an increase in bilirubin concentration and displays lesions and an increasing rupture length.     

Influence of aspirin and iron(III) tetrasulfonated phthalocyanine on bilirubin binding by human serum albumin

The interaction of bilirubin with aspirin-modified human serum albumin (HSA) and the influence of iron tetrasulfonated phthalocyanine on bilirubin binding by the native protein has been studied by difference spectroscopy and circular dichroism measurements. Spectroscopic studies of the systems containing bilirubin and aspirin-modified HSA compared to the analogous systems with the native protein have shown that selective acetylation of albumin at lysine 199 inhibits bilirubin binding by this protein. In both cases, interaction between bilirubin and albumin leads to complex formation at a molar ratio of ligand to protein of 2:1. The studies of the reaction of bilirubin with fragments of albumin produced by reaction with CNBr have demonstrated that one of the strong bilirubin binding sites is located in the M fragment and is close to the high-affinity binding site of aspirin. The other one was found in fragment C. Acetylation of albumin brings about marked conformational change in the protein, which probably accounts for the decrease in its ability to react with anti-HSA antibody. Bilirubin does not change the secondary structure of albumin but, like aspirin, lowers its antigenicity. It has been suggested that the decrease in antigenic properties in this case results from cooperation of the closely neighboring antigenic and bilirubin-binding sites. The studies of the influence of iron(III) tetrasulfonated phthalocyanine on bilirubin binding by HSA suggest that there is no competition between strong sites for iron(III) tetrasulfonated phthalocyanine and bilirubin, but these compounds compete for some of the weaker sites.     

The displacement of albumin bound bilirubin by free fatty acids in vivo

Variations in bilirubinaemia in response to alterations of the free fatty acid level was studied in conscious and unstressed Gunn rats. When only one molecule of bilirubin is bound to albumin (without bilirubin overload), no displacement of bilirubin is observed, even if the protein binds as much as 6 molecules of free fatty acids. After overloading with exogenous unconjugated bilirubin, the second site of fixation of bilirubin on albumin is partly occupied; in this situation, a displacement is observed, but only when more than 3.5 molecules of free fatty acids are simultaneously bound to the protein. In vivo, free fatty acids do not spontaneously reach such levels as those responsable for the observed displacement of bilirubin. In the ranges of bilirubin and free fatty acids concentrations likely to be encountered clinically, free fatty acids might not represent an effective agent of displacement for bilirubin, as it is commonly thought.     

Quantification of volume of tissue damage in stroke using T2- weighed MRI images

We have developed a quantitative technique for scoring of the severity of ischemic damage of the brain using quantitative data of the T2-weighted MRI images of brain in stroke. The principle of the method is the assumption that T2 signal increases proportionally to the severity of ischemic damage of cerebral tissue up to the level equal to intraventricular liquor signal in the case of postinfarction cystic degeneration. Depicting the mean T2-signal from the intraventricular liquor region as Iliq, the signal from ischemic brain area as Iinsult, and from the intact brain as Inorm, obviously, the volume quota of damaged tissue in the total volume of the stroke region is represented by the ratio (Iinsult - Inorm)/(Iliq - Inorm). The total volume of damaged tissue (VDT, cub.cm) in the stroke region is then the following sum taken over all slices i, where the stroke damage can be: VDT = sigma i d.Si.[(Iinsult - Inorm)/(Iliq - Inorm)]i, where d is the slice thickness, Si--area of the ischemic region in the slice i. The quota of damaged tissue in the physical volume of the stroke region is henceforth the following ratio: Q = [sigma i d.Si.[(Iinsult - Inorm)/(Iliq - Inorm)]i]/[sigma i d.Si]. The technique was applied in retrospective analysis of routine MRI studies in 15 patients referred because of acute ischemic stroke. The studies were performed using low-field MRI tomograph Magnetom-Open (Siemens Medical) with field strength 0.22 T. In patients studied during the first day after occurrence of ischemic insult with the minimal degree of acute neurologic deficit, who later have demonstrated clinically full recovery, the VDT was below 20 cm3, and Q was below 10%. In cases with VDT > 25 cm3 and Q > 20% the full regress was not observed in any patient. Henceforth, the quantification of cerebral damage in stroke using quantitative indices based on measurement of T2-parameters over ischemic and intact zones of the brain are of independent prognostic clinical value and improve clinical usefulness of the MRI in ischemic brain stroke.     

Structure-activity relationships and enzyme inhibition of pantothenamide-type pantothenate kinase inhibitors

A set of novel pantothenamide-type analogues of the known Staphylococcus aureus pantothenate kinase (SaPanK) inhibitors, N-pentyl, and N-heptylpantothenamide, was synthesized in three series. The first series of analogues (1-3) were designed as molecular probes of the PanK binding site to elucidate important structure-activity relationships (SAR). The second series of analogues (4-16) were designed using structural information obtained from the Escherichia coli PanK (EcPanK) structure by targeting the pantothenate binding site and the adjacent phenylalanine-lined lipophilic pocket. Insight into the antimicrobial effect of N-pentylpantothenamide (N5-Pan) through its conversion to the antimetabolite ethyldethia-CoA and further incorporation into an inactive acyl carrier protein analogue drove the development of the third series of analogues (17-25) to enhance this effect using substrate-like substitutions. Each of the analogues was screened for enzyme inhibition activity against a panel of pantothenate kinases consisting of EcPanK, Aspergillus nidulans (AnPanK), SaPanK, and the murine isoform (MmPanK1alpha). Series 1 demonstrated only modest inhibitory activity, but did reveal some important SAR findings including stereospecific binding. Series 2 demonstrated a much higher inhibition rate for the entire series and significant inhibition was seen with analogues containing alkyl substituents. Series 3 demonstrated the most preferential inhibition profile, with the highest inhibitory activity against the SaPanK and MmPanK1alpha. The MmPanK1alpha protein was inhibited by a broad spectrum of the compounds, whereas the E. coli enzyme showed greater selectivity. The overall activity data from these analogues suggest a complex and non-enzyme specific SAR for pantothenamide substrate/inhibitors of the different PanK enzymes.