Relationship Between Minor Myocardial Damage and Inflammatory Acute-Phase Reaction in Acute Coronary Syndromes

Background: In severe acute coronary syndromes (ACS) elevation of markers of inflammation and acute phase reaction (APR) like C-reactive protein (CRP) as well as a release of troponin have been reported.Using a high sensitivity troponin T (TnT) test we investigated whether an APR occurs in ACS only in the presence of ischemic myocardial damage. Methods: In 85 patients with ACS C-reactive protein (CRP), serum amyloid A (SAA), fibrinogen, thrombin antithrombin III complexes (TAT) and kallikrein were determined vs. high sensitive TnT (0.02 ng/ml) initially and 2 d later vs. 45 patients with stable angina pectoris and 42 controls. Results: In stable angina pectoris, markers of inflammation and coagulation were slightly elevated (p < 0.05). Initially in ACS elevations of CRP to 1.2 ± 0.3 mg/dl, SAA to 4.8 ± 2.6 mg/dl and fibrinogen to 448 ± 21 mg/dl (all p < 0.01 vs. controls) were found followed by a significant APR (p < 0.01).In the subgroup of TnT positive ACS patients, an APR with increased CRP (4.1 ± 1.3 mg/dl), SAA (20.4 ± 8.3 mg/dl), and fibrinogen (641 ± 45 mg/dl) was detectable (all p < 0.05 vs. TnT negative patients). In contrast, patients without TnT release showed APR markers comparable to patients with stable angina pectoris. Conclusion: Our findings demonstrate an association between myocardial injury in ACS and acute phase reaction as evidenced by several molecular markers. A highly sensitive TnT-test identified myocardial inury in about all patients with APR while a standard TnT cut-off (0.1 ng/ml) missed 32% of these patients. Thus, the APR in patients with ACS is strongly associated with at least minor ischemic myocardial damage and prior findings of an APR independent from myocardial injury are probably based on less sensitive troponin tests.     

Erythrocyte indexes, iron metabolism, and hyperhomocysteinemia in adults with cyanotic congenital cardiac disease

A high percentage of cyanotic adults (37%) with cyanotic congenital cardiac disease (CCD) presented with depleted iron stores (13 of 52) or latent iron deficiency (6 of 52), even in a CCD center in which cyanotic patient phlebotomy is mostly avoided. In many of these patients, hypochromia and microcytosis was frequent, whereas hyperchromia and macrocytosis were relatively common.Furthermore, 50% of patients presented with hyperhomocysteinemia, possibly related to folate or B vitamin deficiencies, which may increase red blood cell size and color, explaining the lack of microcytosis and hypochromia in many cyanotic patients with iron deficiency.     

In Vitro Activity of wALADin Benzimidazoles against Different Life Cycle Stages of Plasmodium Parasites

wALADin1 benzimidazoles are specific inhibitors of δ-aminolevulinic acid dehydratase from Wolbachia endobacteria of filarial nematodes. We report that wALADin1 and two derivatives killed blood stage Plasmodium falciparum in vitro (50% inhibitory concentrations, 39, 7.7, and 12.8 μM, respectively). One of these derivatives inhibited gliding motility of Plasmodium berghei ANKA infectious sporozoites with nanomolar affinity and blocked invasion into hepatocytes but did not affect intrahepatocytic replication. Hence, wALADin1 benzimidazoles are tools to study gliding motility and potential antiplasmodial drug candidates.     

Tropical pyomyositis: an update

Tropical pyomyositis (TP) is a life‐threatening bacterial infection of the skeletal muscle that occurs particularly among children, young adults and those with immunocompromised conditions. The appropriate diagnosis and treatment are often delayed due to its non‐specific signs, leading to fatal consequences. Staphylococcus aureus, especially methicillin‐susceptible S. aureus, is responsible for most TP cases. However, other bacteria (i.e. streptococci, Pseudomonas aeruginosa, Escherichia coli, Klebsiella spp., Candida spp., Mycobacterium spp.) have been reported. This narrative review provides an update on the epidemiology and clinical course of TP. A special focus is laid on the role of toxins (i.e. Panton‐Valentine Leucocidin and α‐toxin) in the pathogenesis of TP and their implication for the clinical management of infection.     

Assessment of Viral Targeted Sequence Capture Using Nanopore Sequencing Directly from Clinical Samples

Shotgun metagenomic sequencing (SMg) enables the simultaneous detection and characterization of viruses in human, animal and environmental samples. However, lack of sensitivity still poses a challenge and may lead to poor detection and data acquisition for detailed analysis. To improve sensitivity, we assessed a broad scope targeted sequence capture (TSC) panel (ViroCap) in both human and animal samples. Moreover, we adjusted TSC for the Oxford Nanopore MinION and compared the performance to an SMg approach. TSC on the Illumina NextSeq served as the gold standard. Overall, TSC increased the viral read count significantly in challenging human samples, with the highest genome coverage achieved using the TSC on the MinION. TSC also improved the genome coverage and sequencing depth in clinically relevant viruses in the animal samples, such as influenza A virus. However, SMg was shown to be adequate for characterizing a highly diverse animal virome. TSC on the MinION was comparable to the NextSeq and can provide a valuable alternative, offering longer reads, portability and lower initial cost. Developing new viral enrichment approaches to detect and characterize significant human and animal viruses is essential for the One Health Initiative.     

St. John's Wort Reduces Beta‐Amyloid Accumulation in a Double Transgenic Alzheimer's Disease Mouse Model—Role of P‐Glycoprotein

The adenosine triphosphate‐binding cassette transport protein P‐glycoprotein (ABCB1) is involved in the export of beta‐amyloid from the brain into the blood, and there is evidence that age‐associated deficits in cerebral P‐glycoprotein content may be involved in Alzheimer''s disease pathogenesis. P‐glycoprotein function and expression can be pharmacologically induced by a variety of compounds including extracts of Hypericum perforatum (St. John''s Wort). To clarify the effect of St. John''s Wort on the accumulation of beta‐amyloid and P‐glycoprotein expression in the brain, St. John''s Wort extract (final hyperforin concentration 5%) was fed to 30‐day‐old male C57BL/6J‐APP/PS1 ^+/− mice over a period of 60 or 120 days, respectively. Age‐matched male C57BL/6J‐APP/PS1 ^+/− mice receiving a St. John''s Wort‐free diet served as controls. Mice receiving St. John''s Wort extract showed (i) significant reductions of parenchymal beta‐amyloid 1–40 and 1–42 accumulation; and (ii) moderate, but statistically significant increases in cerebrovascular P‐glycoprotein expression. Thus, the induction of cerebrovascular P‐glycoprotein may be a novel therapeutic strategy to protect the brain from beta‐amyloid accumulation, and thereby impede the progression of Alzheimer''s disease.