Inhibition of Feline Immunodeficiency Virus Infectionin Vitroby Envelope Glycoprotein Synthetic Peptides

Sixty-six 20- to 23-amino-acid synthetic peptides, partially overlapping by 10–12 amino acids, spanning the entire sequence of the envelope SU and TM glycoproteins of the Petaluma isolate of FIV, have been used to investigate the Env domains involved in viral infection. Peptides 5 to 7, spanning amino acids²²⁵E–P²⁶⁴located in a conserved region of the SU protein, and peptides 58 to 61, spanning amino acids⁷⁵⁷N–P⁸⁰⁶and encompassing hypervariable region 8 of TM protein, exhibited a remarkable and specific antiviral effect against the homologous and one heterologous isolate, as judged by inhibition of FIV-induced syncytium formation and p25 production in CrFK cells. Peptides 5 and 7, but not peptides 58 and 59, also inhibited viral replication of a fresh FIV isolate on nontransformed lymphoid cells. By flow cytometry, peptides 5, 7, 58, and 59 were shown to bind the surface of FIV permissive cells. The antiviral activity of peptides 5 and 7, however, was time-dependent, as inhibition of FIV replication was seen when the peptides were administered before or within 3 hr after virus inoculation; in contrast, TM peptides 58 and 59 exerted a potent inhibitory effect when added up to 24 hr after virus inoculation. Circular dychroism analysis showed that peptide 5 folds to a helical conformation in the presence of a hydrophobic environment. Although the basis for the antiviral action of the peptides is not understood, our data suggest that the inhibitory peptides may act by interacting with cell-surface molecules involved in viral infection.     

Sleep onset and cardiovascular activity in primary insomnia

The transition from wakefulness to sleep is characterized typically by a shift from sympathetic to parasympathetic regulation. Physiological functions, depending on the neurovegetative system, decrease overall. Previous studies have shown cardiovascular and electroencephalographic hyperactivity during wakefulness and sleep in insomniacs compared with normal sleepers, but there is very little evidence of this in the process of sleep onset. The purpose of this study was to compare cardiovascular and autonomic responses before and after falling asleep in eight insomniacs (who met DSM‐IV criteria for primary insomnia) and eight normal sleepers. Non‐invasive measures of heart rate (HR), stroke volume (SV), cardiac output (CO) and pre‐ejection period (PEP) were collected by impedance cardiography during a night of polysomnographic recording. Frequency domain measures [low‐frequency (LF), high‐frequency (HF)] of heart rate variability (HRV) were also estimated. Decrements in HR and CO and increases in SV and HF normalized units (n.u.) were found in both groups after sleep onset compared with wakefulness. Conversely, PEP (related inversely to sympathetic β‐adrenergic activity) showed increases after sleep onset in controls, but remained unchanged in insomniacs. PEP was also significantly lower in insomniacs than in normal sleepers in both conditions. These data suggest that, whereas normal sleepers follow the expected progressive autonomic drop, constant sympathetic hyperactivation is detected in insomniacs. These results support the aetiological hypothesis of physiological hyperarousal underlying primary insomnia.     

Thrombelastographic observations on the characteristics of hemophilic,thrombocytopenic and heparinized blood

1. Thrombelastographic determinations were made in cases of AHG-, PTC- and PTA-deficiencies, in thrombocytopenias and in normal plasmas after theaddition, in vitro, of heparin and synthetic heparin-like substances.

2. The components of the thrombelastogram (TEG) were correlated withrespect to the reaction time (r), the rate of clot formations (k), and the maximalamplitude (ma).

3. The differentiation of the hemophilic and thrombocytopenic syndromes wasmade on the basis of the typical variations of r, k and ma: prolonged r and k inhemophilia, prolonged k and decreased ma in thrombocytopenias.

4. The behavior of heparinized blood was characterized by a hemophilia-likeprolongation of r and k and a thrombocytopenic-like decrease of ma, with variations depending on the compound used.

5. The correlations between the r, k and ma values of TEG are suggested forthe evaluation of thrombelastography.

Submitted on April 8, 1955 Accepted on August 26, 1955