Intracellular Reservoir of Streptococcus pyogenes In Vivo: A Possible Explanation for Recurrent Pharyngotonsillitis

Numerous theories have been presented that attempt to explain the frequent recurrences of pharyngotonsillitis caused by Streptococcus pyogenes; these recurrences occur after seemingly adequate antibiotic treatment. We previously have demonstrated that S pyogenes can survive for up to 7 days intracellularly in immortalized human respiratory epithelial cells grown in an antibiotic supplemented medium. Viable S pyogenes were externalized and established an extracellular infection, whenever the extracellular antibiotic was removed. We have investigated the presence of intracellular S pyogenes in two in vivo studies using respiratory epithelial cells collected from patients with tonsillitis and the tonsils of asymptomatic carriers. Electron microscopy and immunohistochemistry demonstrated intracellular S pyogenes in pharyngeal epithelial cells in 13 of 14 patients with tonsillitis (93%). Furthermore, intracellular S pyogenes were found in macrophage-like cells in eight (73%) and in epithelial cells in four (36%) tonsils from 11 asymptomatic S pyogenes carriers. These in vivo data strongly support the hypothesis that intracellular S pyogenes can constitute a reservoir of bacteria with the potential to cause reinfections     

Difference in pathogenesis between herpes simplex virus type 1 encephalitis and tick-borne encephalitis demonstrated by means of cerebrospinal fluid markers of glial and neuronal destruction

We determined the extent of neuronal and glial cell destruction in 13 patients with herpes simplex type 1 (HSV-1) encephalitis, 15 patients with tick-borne encephalitis (TBE), and 20 noninfectious controls by analyzing the cerebrospinal fluid (CSF) concentrations of neurofilament protein (a marker of neurons, mainly axons), neuron-specific enolase (a marker of neurons, mainly somas), glial fibrillary acidic protein, and S-100 protein (markers of astrocytes). In addition, in patients with HSV-1 encephalitis CSF samples were collected serially before 7, 8-14, and 18-49 days and 3-10 months after the onset of neurological symptoms. In the acute stage of HSV-1 encephalitis we found markedly higher CSF levels of the cell damage markers than in patients with TBE. The concentration of cell damage markers in HSV-1 encephalitis decreased within 45 days after acute infection, except for neurofilament protein. The CSF concentrations of neurofilament protein increased during the second week, remained extremely high throughout the next month, and decrease thereafter. The changes in these markers of neuronal and glial destruction demonstrate the neuronal and astroglial cell damage during the first month after HSV-1 encephalitis. In contrast, most patients with TBE had signs only of slight astrogliosis, except for two patients with paresis.     

Seawater activated TiO2 photocatalyst for degradation of organic compounds

The world's oceans are polluted by a continuous inflow of plastic. Plastic fragments finally into microplastic, which can be taken up, for example by plankton, and subsequently by the entire ocean food web. An approach to reduce plastic pollution constitutes the accelerated microplastic degradation in marine environments. TiO₂ (anatase) is commonly used as an oxidative photocatalyst and well known to catalyze the degradation of organic compounds upon UV irradiation.In this study, a selective activation of TiO₂ (anatase) particles encapsulated by Ca- or Sr-polyphosphate is presented. The TiO₂ polyphosphate core-shell particles are envisaged as additives in plastic products. The highly concentrated cations from seawater, viz. Na⁺ and Mg²⁺, displace the Ca²⁺ or Sr²⁺ cations from the polyphosphate shell. As a result, the polyphosphate coating dissolves and thus the photocatalytically active TiO₂ core is released. The stability of the TiO₂ polyphosphate particles in potable water and the seawater activated disintegration of methylene blue, methyl methacrylate, terephtalic acid, and poly(vinyl alcohol) was shown. It has been demonstrated, that the sweetwater stable polyphosphate coating degrades in the presence of seawater, which could be monitored by the activation of the TiO₂ (anatase) photocatalyst.     

Pharmacokinetics of ampicillin and its prodrugs bacampicillin and pivampicillin in man

Five healthy fasting male subjects were each given single doses of intravenous ampicillin (471 mg), oral ampicillin tablets (495 mg), oral bacampicillin hydrochloride tablets (562 mg ampicillin equivalent), and oral pivampicillin hydrochloride capsules (491 mg ampicillin equivalent) in a crossover experiment. The resulting concentrations of ampicillin were determined in plasma and urine. The pharmacokinetic analysis was made according to a two-compartment open model. The total distribution volume of unbound ampicillin during the disposition phase was 0.247 ± 0.045 (sd) liter/kg, which is only slightly more than the extracellular fluid, suggesting that tissue binding and intracellular distribution of ampicillin are limited. The bioavailability of the esters bacampicillin (86 ± 11%) and pivampicillin (92± 18%) was significantly greater than that of ampicillin (62 ± 17%); however, the difference between the esters was not statistically significant. The absorption for all drugs given orally proceeded at a constant rate, suggesting zero-order release rates from the products. The absorption rate was highest for bacampicillin (0.89 ± 0.39% of dose absorbed per minute), followed by pivampicillin (0.64 ± 0.19) and ampicillin (0.58 ± 0.16). Bacampicillin also had the shortest lag time for the start of absorption (7.0 ± 0.9 min) under the present conditions. Thus, in comparison with ampicillin, the esters have a higher bioavailability, which, in fact, is close to the theoretically highest possible value by clearance concepts. The higher bioavailability in connection with higher absorption rates may be clinically important in ampicillin treatment by the oral route.This work was supported by the Swedish Medical Research Council, Project No. 522 (L. O. B.).     

Risk assessment in COVID‐19: Prognostic importance of cardiovascular parameters

BackgroundCardiovascular risk factors and comorbidities are highly prevalent among COVID‐19 patients and are associated with worse outcomes.HypothesisWe therefore investigated if established cardiovascular risk assessment models could efficiently predict adverse outcomes in COVID‐19. Furthermore, we aimed to generate novel risk scores including various cardiovascular parameters for prediction of short‐ and midterm outcomes in COVID‐19.MethodsWe included 441 consecutive patients diagnosed with SARS‐CoV‐2 infection. Patients were followed‐up for 30 days after the hospital admission for all‐cause mortality (ACM), venous/arterial thromboembolism, and mechanical ventilation. We further followed up the patients for post‐COVID‐19 syndrome for 6 months and occurrence of myocarditis, heart failure, acute coronary syndrome (ACS), and rhythm events in a 12‐month follow‐up. Discrimination performance of DAPT, GRACE 2.0, PARIS‐CTE, PREDICT‐STABLE, CHA2‐DS2‐VASc, HAS‐BLED, PARIS‐MB, PRECISE‐DAPT scores for selected endpoints was evaluated by ROC‐analysis.ResultsOut of established risk assessment models, GRACE 2.0 score performed best in predicting combined endpoint and ACM. Risk assessment models including age, cardiovascular risk factors, echocardiographic parameters, and biomarkers, were generated and could successfully predict the combined endpoint, ACM, venous/arterial thromboembolism, need for mechanical ventilation, myocarditis, ACS, heart failure, and rhythm events. Prediction of post‐COVID‐19 syndrome was poor.ConclusionRisk assessment models including age, laboratory parameters, cardiovascular risk factors, and echocardiographic parameters showed good discrimination performance for adverse short‐ and midterm outcomes in COVID‐19 and outweighed discrimination performance of established cardiovascular risk assessment models.