Myocardial ischemia stimulates catecholamine synthesis and catabolism in the dog adrenal medulla

The effects of regional ischemia of the myocardium upon metabolism and catabolism of catecholamines were studied in the dog adrenal medulla. Regional ischemia was induced by ligating a small branch of the left anterior descending coronary artery for 1 or 24 hours. Sham-operated controls were run in parallel. Coronary ligation for 24 hours resulted in a decrease in the level of epinephrine and an increase in the level of dopamine in the adrenal medulla, and also resulted in an increase in the activities of the phenylethanolamine-N-methyltransferase (PNMT), monoamine oxidase, and catechol-O-methyltransferase. The results after coronary ligation for 1 hour were essentially the same as those after coronary ligation for 24 hours, except that the activity of PNMT decreased. These results suggest that both synthesis and catabolism of catecholamines in the adrenal medulla are accelerated during coronary ligation for a period of 1 to 24 hours.     

Geometric architecture of viruses

In the current SARS-CoV-2 disease (COVID-19) pandemic, the structural understanding of new emerging viruses in relation to developing effective treatment and interventions are very necessary. Viruses present remarkable differences in geometric shapes, sizes, molecular compositions and organizations. A detailed structural knowledge of a virion is essential for understanding the mechanisms of capsid assembly/disassembly, antigenicity, cell-receptor interaction, and designing therapeutic strategies. X-ray crystallography, cryo-electron microscopy and molecular simulations have elucidated atomic-level structure of several viruses. In view of this, a recently determined crystal structure of SARS-CoV-2 nucleocapsid has revealed its architecture and self-assembly very similar to that of the SARS-CoV-1 and the Middle-East respiratory syndrome virus (MERS-CoV). In structure determination, capsid symmetry is an important factor greatly contributing to its stability and balance between the packaged genome and envelope. Since the capsid protein subunits are asymmetrical, the maximum number of inter-subunit interactions can be established only when they are arranged symmetrically. Therefore, a stable capsid must be in a perfect symmetry and lowest possible free-energy. Isometric virions are spherical but geometrically icosahedrons as compared to complex virions that are both isometric and helical. Enveloped icosahedral or helical viruses are very common in animals but rare in plants and bacteria. Icosahedral capsids are defined by triangulation number (T = 1, 3, 4, 13, etc.), i.e., the identical equilateral-triangles formed of subunits. Biologically significant defective capsids with or without nucleic acids are common in enveloped alpha-, flavi- and hepadnaviruses. The self-assembling, stable and non-infectious virus-like particles have been widely exploited as vaccine candidates and therapeutic molecules delivery vehicles.     

Comparative study of the effects of isatin, an endogenous MAO-inhibitor, and selegiline on bradykinesia and dopamine levels in a rat model of Parkinson's disease induced by the Japanese encephalitis virus

We previously reported that exogenously administered isatin, an endogenous monoamine oxidase (MAO) inhibitor, significantly increased acetylcholine (ACh) and dopamine (DA) levels in the rat striatum. Selegiline [(-)-deprenil] was developed as a MAO-B inhibitor more than 30 years ago and widely used in the treatment of Parkinson's disease. Effects of isatin or selegiline were investigated in Japanese encephalitis virus (JEV)-induced post-encephalitic parkinsonism rats by a pole test for detecting motor activity and by the determination of biogenic amine levels. Motor activity of JEV-induced rats receiving isatin (100 mg/kg per day for 1 week, i.p.) or selegiline (0.2 mg/kg per day for 1 week, i.p.) was significantly improved compared with that of untreated JEV-infected rats. Both isatin and selegiline prevented the decrease in striatal DA levels in JEV-rats. The increased turnover of DA (DOPAC/DA) induced by JEV was significantly inhibited by isatin, but not by selegiline. These results suggested that exogenously administered isatin and selegiline can improve JEV-induced parkinsonism by increasing DA concentrations in the striatum.     

Modeling of Melt Flow and Heat Transfer in Stationary Gas Tungsten Arc Welding with Vertical and Tilted Torches

A 3D numerical simulation was conducted to study the transient development of temperature distribution in stationary gas tungsten arc welding with filler wire. Heat transfer to the filler wire and the workpiece was investigated with vertical (90°) and titled (70°) torches. Heat flux, current flux, and gas drag force were calculated from the steady-state simulation of the arc. The temperature in the filler wire was determined at three different time intervals: 0.12 s, 0.24 s, and 0.36 s. The filler wire was assumed not to deform during this short time, and was therefore simulated as solid. The temperature in the workpiece was calculated at the same intervals using heat flux, current flux, gas drag force, Marangoni convection, and buoyancy. It should be noted that heat transfer to the filler wire was faster with the titled torch compared to the vertical torch. Heat flux to the workpiece was asymmetrical with both the vertical and tilted torches when the filler wire was fully inserted into the arc. It was found that the overall trends of temperature contours for both the arc and the workpiece were in good agreement. It was also observed that more heat was transferred to the filler wire with the 70° torch compared with the 90° torch. The melted volume of the filler wire (volume above 1750 °K) was 12 mm³ with the 70° torch, compared to 9.2 mm³ with the 90° torch.     

Inhibition of hepatitis B virus DNA replicative intermediate forms by recombinant interferon-γ

AIM: To evaluate the in vitro anti-HBV activity of recombinant human IFN-γ, alone and in combination with lamivudine.METHODS: A recombinant baculovirus-HBV/HepG2 culture system was developed which could support productive HBV infection in vitro. Expression of HBsAg and HBeAg in infected HepG2 culture medium was detected by commercial enzyme immunoassays. HBV DNA replication intermediates were detected in infected cells by Southern hybridization and viral DNA load was determined by dot hybridization.RESULTS: IFN-γ at 0.1 to 5 μg/L efficiently down regulated HBsAg expression in transduced HepG2 cells.At 5 μg/L, IFN-γ also suppressed HBV DNA replication in these cells. While treatment with a combination of lamivudine and IFN-γ showed no additive effect,sequential treatment first with lamivudine and then IFN-γ was found to be promising. In this culture system the best HBV suppression was observed with a pulse of 2 μmol/L lamivudine for two days, followed by 1 μg/L IFN-γ for another four days. Compared to treatment with lamivudine alone, the sequential use of 0.2 μmol/L lamivudine for two days, followed by 5 μg/L IFN-γ for six days showed a 72% reduction in HBV cccDNA pool.CONCLUSION: This in vitro study warrants further evaluation of a combination of IFN-γ and lamivudine,especially in IFN-α non-responder chronic hepatitis B patients. A reduced duration of lamivudine treatment would also restrict the emergence of drug-resistant HBV mutants.     

Methicillin-resistant Staphylococcus aureus infection or colonization present at hospital admission: multivariable risk factor screening to increase efficiency of surveillance culturing

Identifying methicillin-resistant Staphylococcus aureus (MRSA) colonization or infection present at admission has become important in reducing subsequent nosocomial transmission, but the most efficient surveillance methods remain to be defined. We performed anterior nares surveillance cultures of all patients upon admission to and discharge from the general internal medicine floor in our community hospital over a 7-week period, and patients completed a questionnaire on MRSA risk factors. Of the 401 patients, 41 (10.2%) had MRSA upon admission. Of the 48 risk measures analyzed, 10 were significantly associated with admission MRSA, and 7 of these were independently associated in stepwise logistic regression analysis. Factor analysis identified eight latent variables that contained most of the predictive information in the 48 risk measures. Repeat logistic regression analysis including the latent variables revealed three independent risk measures for admission MRSA: a nursing home stay (relative risk [RR], 6.18; 95% confidence interval [95% CI], 3.56 to 10.72; P < 0.0001), prior MRSA infection (RR, 3.97; 95% CI, 1.94 to 8.12; P = 0.0002), and the third latent variable (factor 3; RR, 3.14; 95% CI, 1.56 to 6.31; P = 0.0013), representing the combined effects of homelessness, jail stay, promiscuity, intravenous drug use, and other drug use. Multivariable models had greater sensitivity at detecting admission MRSA than any single risk measure and allowed detection of 78% to 90% of admission MRSA from admission surveillance cultures on 46% to 58% of admissions. If confirmed in additional studies, multivariable questionnaire screening at admission might identify a subset of admissions for surveillance cultures that would more efficiently identify most admission MRSA.