Furosemide inhibits regenerative cortical spreading depression in anaesthetized cats

Ionic perturbations occur during cortical spreading depression (SD), a phenomenon implicated in migraine pathophysiology. We studied the effect of 0.2,2 and 20 mg kg⁻¹ iv ( n =4) furosemide on cortical direct current (d.c.) potential, cerebrovascular laser Doppler flux (rCBF_LDF), artery diameter and NO concentration in the parietal cortex of the anaesthetized cat during repetitive SD. In vehicle treated animals ( n =4), SD activity was sustained for 50 1.8 min. However, duration of SD activity was significantly reduced when compared to vehicle to 39 6.6 ( n =4), 3.1 8.3 ( n =4) and 27.3 11.3 min ( n =4), at 0.2, 2 and 20 mg kg⁻¹ iv furosemide respectively. It is hypothesized that the mechanism of inhibition of SD d.c. activity by furosemide may be through alterations in cortica ion buffering capacity or inhibition of cell swelling in neurones or glia. These mechanisms may represent potential novel drug targets in future migraine therapy.     

Recombinant immunoblot assay reaction patterns and hepatitis C virus RNA in blood donors and non-A, non-B hepatitis patients

To establish the value of the second-generation recombinant immunoblot assay (RIBA-2) and cDNA polymerase chain reaction (cDNA PCR) for confirmation of hepatitis C virus (HCV) infection, anti-HCV reaction patterns and the presence of HCV RNA were examined in 610 blood donors and 255 non-A, non-B hepatitis patients who were positive or indeterminate in RIBA-2. Of RIBA-2-positive donors (n = 191) and patients (n = 224), 75.4 and 89.7 percent, respectively, were HCV RNA positive. The most frequently observed anti-HCV recognition patterns in HCV RNA-positive donors and patients were c22, c33c, and c100 and/or 5- 1-1 (67.3%, 57.7%) and c22, c33c (24.8%, 29.3%). Among subjects with a RIBA-2-indeterminate result, HCV RNA was detected more often in patients (n = 31) than in donors (n = 419): 67.7 and 2.1 percent, respectively. In viremic persons with single-band reactivity in RIBA-2, this reactivity was always directed against either c22 or c33c. HCV RNA was detected by cDNA PCR in none of 162 persons with only anti-c100 and/or anti-5-1-1 reactivity. Therefore, RIBA-2 reactivity against c100 in combination with 5-1-1 should not be considered positive but indeterminate. In RIBA-2-indeterminate persons, HCV RNA detection is necessary for reliable confirmation of HCV infection.     

Impairment of human NK cell cytotoxic activity and cytokine release by cigarette smoke

NK cells play essential roles in innate host defense against microbial infections and tumor surveillance. Although evidence suggests that smoking has adverse effects on the immune system, little is known about whether smoking compromises NK cell effector functions. In this study, we show that cigarette smoke-conditioned medium (SCM) dose-dependently inhibits in vitro IFN-gamma production by polyinosinic:polycytidylic acid (poly I:C)-activated PBMC and NK cells isolated from nonsmoking individuals. Similarly, SCM attenuated poly I:C-induced TNF-alpha production by PBMC and NK cells. The inhibitory effect of cigarette smoke on TNF-alpha production was reversible. PBMC and NK cells isolated from smokers displayed significant reduction of IFN-gamma and TNF-alpha secretions compared with nonsmokers in response to poly I:C activation. We further observed that SCM attenuated NK cell cytotoxic activity, which was associated with decreased up-regulation of perforin expression. Attenuated cytotoxic activity was also observed in PBMCs isolated from smokers. Finally, anti-IL-12 mAb-blocking data revealed that an attenuation of IFN-gamma production by PBMC was indirect, likely via attenuation of IL-12 production, and the effect on NK cells was IL-12-independent. Our data indicate that cigarette smoke compromises function of human NK cells. This may contribute to a higher incidence of viral infections and cancer among smokers.     

The role of toll-like receptor ligands/agonists in protection against genital HSV-2 infection

Control of virus replication initially depends on rapid activation of the innate immune responses. Toll-like receptor (TLR) ligands are potent inducers of innate immunity against viral infections, including herpes simplex virus (HSV). HSV-2 is currently one of the most common sexually transmitted infections in developed nations and is becoming more prevalent in adolescents. HSV-2 infects the genital mucosa and is associated with an increased risk of obtaining other sexually transmitted infections such as HIV. There is currently no vaccine available against HSV-2. In the last several years, there has been an interest in utilizing Toll-like receptor (TLR) ligands to initiate innate immune responses in order to provide an early line of defence against viral replication. This review highlights recent studies investigating the effect of various TLR ligands on genital HSV-2 infection. A considerable body of information has been published on the effect of local delivery of TLR ligands on HSV-2 replication in genital mucosa. We have outlined ligands that have a potential to provide protection against HSV-2 infection. In addition, we have presented possible mechanisms by which the local delivery of TLR ligands provides innate protection against genital HSV-2.     

How we dealt with the double whammy! Acute pulmonary embolism with abdominal aortic clot and renal infarcts

Pulmonary embolism (PE) is the third most common cause of cardiovascular mortality in the United States, and the submassive PE accounts for 20%-25% of all acute PE. In the last decade, endovascular therapy with catheter-directed thrombolysis (CDT) intervention has shown great success in the treatment of submassive PE. There is limited data regarding using these devices to treat patients with concomitant abdominal aortic and renal vessel clots. Herein, we present a case of a 23-year-old male who presented with submassive PE associated with abdominal aortic thrombosis and renal infarcts. The patient was successfully treated with CDT with complete resolution of pulmonary and bilateral renal artery clots.