A breakdown of the blood-brain barrier occurred in mice inoculated intracerebrally (i.c.) or intraperitoneally (i.p.) with dengue virus type 2 (DEN2). This resulted in leakage of protein-bound Evans blue dye and 51Cr-labelled erythrocytes into the brain tissue. The leakage increased with time after infection and coincided with an increase of a DEN2-induced cytokine, the cytotoxic factor (CF), in the spleens of such mice. The titres of virus in the brain increased exponentially in i.c. inoculated mice but the virus was not detected in brains of mice given DEN2 by the i.p. route. Similar breakdown of the blood-brain barrier also occurred in mice inoculated intravenously with CF; the damage was dose-dependent and the vascular integrity was restored during the 3 h period after inoculation. Treatment of mice with antihistamine drugs, blocking H1 or H2 receptors, decreased the DEN2-induced protein leakage by up to 50% in i.c. inoculated mice and up to 92 % in those inoculated i.p. Indomethacin, a prostaglandin synthetase inhibitor, had no effect. In i.c. inoculated mice protein leakage was inhibited by about 60% by treatment with CFspecific (CFA) or DEN2-specific antisera (DEN2A) whereas protection was complete with the combined treatment with both antisera. On the other hand, in i.p. inoculated mice the inhibition of protein leakage was 80 to 89% with CFA. These findings show a breakdown of the blood-brain barrier leading to cerebral oedema during DEN2 infection which is mediated via the release of histamine by a virus-induced cytokine.

Abstract-Behavioral changes are believed to be a sensitive indicator of toxicant exposure but can be very difficult to quantify. Using the free-living soil nematode Caenorhabditis elegans, a computer tracking system was used that measures several behavioral parameters for approximately 100 subjects on a real-time basis. Toxicant exposures can be performed in soil, on agar plates, or in aquatic media. Following the exposure period, the worms are transferred to a thin-layered agar slab for viewing in dark-field illumination by a video camera interfaced directly to a computer. Information can be obtained on a number of behavioral parameters including number of subjects moving, their individual rates of locomotion, and the frequency of change in direction. Exposure to five metals (Pb, Cu, Cd, Al, and Zn) were tested in this study to evaluate behavioral changes in the worm. The nematodes were exposed for 24 h to concentrations of an individual metal in aquatic medium representing the interstitial pore water within the soil. Under identical conditions, concurrent LC50 and BC50 (concentration at which movement is reduced by 50% compared with controls) values were determined for each metal tested. The results from computer tracking revealed significant changes in rate of locomotion at concentrations of less than 10% of the respective LC50 value.

Vestibular hair cells transduce mechanical displacements of their hair bundles into an electrical receptor potential which modulates transmitter release and subsequent action potential firing in afferent neurons. To probe ionic mechanisms underlying sensory coding in vestibular calyces, we used the whole-cell patch-clamp technique to record action potentials and K + currents from afferent calyx terminals isolated from the semicircular canals of Mongolian gerbils. Calyx terminals showed minimal current at the mean zero-current potential (−60 mV), but two types of outward K + currents were identified at potentials above −50 mV. The first current was a rapidly activating and inactivating K + current that was blocked by 4-aminopyridine (4-AP, 2.5 mM) and BDS-I (up to 250 nM). The time constant for activation of this current decreased with membrane depolarization to a minimum value of ∼1 ms. The 4-AP-sensitive current showed steady-state inactivation with a half-inactivation of approximately −70 mV. A second, more slowly activating current (activation time constant was 8.5±0.7 ms at −8 mV) was sensitive to TEA (30 mM). The TEA-sensitive current also showed steady-state inactivation with a half-inactivation of −95.4±1.4 mV, following 500-ms duration conditioning pulses. A combination of 4-AP and TEA blocked ∼90% of the total outward current.In current clamp, single Na + -dependent action potentials were evoked following hyperpolarization to potentials more negative than the resting potential. 4-AP application increased action potential width, whereas TEA both increased the width and greatly reduced repolarization of the action potential.

A 26 residue peptide (Am 2766) with the sequence CKQAGESCDIFSQNCCVG-TCAFICIE-NH 2 has been isolated and puri¢ed from the venom of the molluscivorous snail, Conus amadis, collected o¡ the southeastern coast of India. Chemical modi¢cation and mass spectrometric studies establish that Am 2766 has three disul¢de bridges. C-terminal amidation has been demonstrated by mass measurements on the C-terminal fragments obtained by proteolysis. Sequence alignments establish that Am 2766 belongs to the N N-conotoxin family. Am 2766 inhibits the decay of the sodium current in brain rNav1.2a voltage-gated Na + channel, stably expressed in Chinese hamster ovary cells. Unlike N N-conotoxins have previously been isolated from molluscivorous snails, Am 2766 inhibits inactivation of mammalian sodium channels. ß

The current pandemic coronavirus, SARS-CoV-2, is known to cause severe infection (COVID-19) in patients with comorbidities, particularly cancer or an immunosuppressed state. Most healthcare systems in the country are likely to be overwhelmed soon if the pandemic moves to a stage of community transmission. Currently, limited evidence is available for managing patients with hematological disorders during the COVID-19 pandemic. The current review summarises the possible challenges clinicians are likely to face, key considerations to guide decision making, and possible solutions to the anticipated challenges. Disease specific recommendations and possible guidance for decision making have been suggested for most hematologic diseases that are feasible in our health setup. It is not meant to replace individual clinical judgment, but to provide a template to formulate local policies.