Clinical epidemiology and survival of progressive multifocal leukoencephalopathy in the era of highly active antiretroviral therapy: Data from the Italian Registry Investigative Neuro AIDS (IRINA)

Human immunodeficiency virus (HIV)-associated progressive multifocal leukoencephalopathy (PML) remains a relevant clinical problem even in the era of highly active antiretroviral therapy (HAART). Aims of the study were to analyze clinical and treatment-related features and the survival probability of PML patients observed within the Italian Registry Investigative Neuro AIDS (IRINA) during a 29-month period of HAART. Intravenous drug use, the presence of focal signs, and the involvement of white matter at neuroradiology increased the risk of having PML. A reduced probability of PML was observed when meningeal signs were reported. Patients starting HAART at PML diagnosis and previously naïve for antiretrovirals showed significantly higher 1-year probability of survival (.58), compared to those continuing HAART (.24), or never receiving HAART (.00). Higher CD4 cell count were associated with a higher survival probability (.45). At multivariate analysis, a younger age, higher CD4, starting HAART at PML diagnosis, the absence of previous acquired immunodeficiency syndrome (AIDS)-defining events, and the absence of a severe neurologic impairment were all associated with a reduced hazard of death. The use of cidofovir showed a trend towards a reduced risk of death.     

Accelerated elimination from the circulation of homologous aged red blood cells in rats bearing anti-spectrin antibodies

In order to analyse a possible role of anti-spectrin antibodies in the clearance of aged red blood cells (RBC), a homologous system was employed, whereby a population of aged RBC, obtained by hypertransfusion, was injected into rats bearing a high level of anti-spectrin antibodies, following immunization with spectrin. The aged RBC bound the anti-spectrin antibodies 'in vitro' and were eliminated from circulation in spectrin-treated rats at a faster rate than in control rats with naturally occurring antibodies. The analysis of the clearance curves revealed aged RBC of heterogeneous lifespans: two principal populations of short- and longer-living could be identified. In rats with anti-spectrin antibodies, the survival of the short-living population was further reduced. However, the similar kinetics of elimination of aged RBC in the two groups (with naturally-occurring and induced antibodies, respectively) suggest that anti-spectrin antibodies strengthened the intervention of the naturally-occurring ones. On the basis of these results, we assume that during their aging in circulation, RBC can accumulate surface alterations to make spectrin accessible to antibodies so that, in addition to anti-band 3 antibodies, anti-spectrin antibodies may contribute to their elimination.     

Characterization and partial purification of a lectin from the hemolymph of the white shrimp Litopenaeus schmitti

The agglutinating activity of the hemolymph of Litopenaeus schmitti is insensitive to calcium and specific for acetylated sugars, particularly sialic acid (Neu5Ac) and O-sialoglycoconjugates (bovine submaxillary mucin) and has varying specificity for different LPS, which may suggest a putative role in microorganism recognition. Affinity chromatography on fetuin-agarose of the agglutinin resulted in a 220 kDa band (lectin), and a 82.5 kDa band, which probably is hemocyanin. The 220 kDa protein consists of 31 and 34 kDa subunits, suggesting that this lectin is multimeric. The lectin molecular mass was estimated by gel filtration to be 153+/-10 kDa. The hemolymph of L. schmitti comprises at least another soluble lectin, with distinct chemical and carbohydrate specificity than the 220 kDa lectin.     

Effects of nucleus basolateralis amygdalae neurotoxic lesions on aversive conditioning in the rat

After bilateral stereotaxic administration of ibotenic acid on the n. basolateralis amygdalae, male adult rats were tested in the light-dark box apparatus to measure the time-course of the acquisition and retention of passive and active avoidance responses. The results show that after the lesions both passive avoidance and active avoidance acquisition were impaired. Passive avoidance responses were retained quite well, while active avoidance responses disappeared quickly. Conditioned freezing was almost completely absent. Thus it appears that the n. basolateralis plays a facilitatory role in all the conditioned responses which were investigated.     

SARS-CoV-2 Specific Immune Response and Inflammatory Profile in Advanced HIV-Infected Persons during a COVID-19 Outbreak

The main aim of this study was to describe the clinical and immunological outcomes, as well as the inflammatory profile, of patients with advanced HIV in an assisted-living facility in which an outbreak of SARS-CoV-2 occurred. SARS-CoV-2 humoral and specific T-cell response were analyzed in patients with HIV infection and COVID-19; as a secondary objective of the analysis, levels of the inflammatory markers (IL-1β, IL-6, IL-8, and TNFα) were tested in the HIV/COVID-19 group, in HIV-positive patients without COVID-19, and in HIV-negative patients with mild/moderate COVID-19. Antibody kinetics and ability to neutralize SARS-CoV-2 were evaluated by ELISA assay, as well as the inflammatory cytokines; SARS-CoV-2 specific T-cell response was quantified by ELISpot assay. Mann–Whitney or Kruskal–Wallis tests were used for comparisons. Thirty patients were included with the following demographics: age, 57 years old (IQR, 53–62); 76% male; median HIV duration of infection, 18 years (15–29); nadir of CD4, 57/mmc (23–100) current CD4 count, 348/mmc (186–565). Furthermore, 83% had at least one comorbidity. The severity of COVID-19 was mild/moderate, and the overall mortality rate was 10% (3/30). Additionally, 90% of patients showed positive antibody titers and neutralizing activity, with a 100% positive SARS-CoV-2 specific T-cell response over time, suggesting the ability to induce an effective specific immunity. Significantly higher levels of IL-6, IL-8, and TNF-α in COVID-19 without HIV vs. HIV/COVID-19 patients (p < 0.05) were observed. HIV infection did not seem to negatively impact COVID-19-related inflammatory state and immunity. Further data are mandatory to evaluate the persistence of these immunity and its ability to expand after exposure and/or vaccination.     

Pegylated interferon plus ribavirin for recurrent Hepatitis C infection after liver transplantation in naïve and non-responder patients on a stable immunosuppressive regimen

BACKGROUND: Hepatitis C virus recurrence after liver transplantation is universal, leading to chronic hepatitis and cirrhosis. AIMS AND PATIENTS: We evaluated the efficacy and safety of pegylated interferon and ribavirin in 20 patients with recurrent Hepatitis C virus after liver transplantation (10 na?ve and 10 non-responders to a previous interferon course). METHODS: Treatment consisted of pegylated interferon alfa-2b (1.0 microg/kg once weekly) and ribavirin (600 mg/daily) for at least 6 months. Therapy continued for an additional 6 months only in patients with undetectable serum Hepatitis C virus-RNA or >2 log drop from baseline levels. RESULTS: Eleven out of 20 patients (55%) completed 1 year of treatment. Nine patients (45%) had undetectable Hepatitis C virus-RNA at the end of treatment, six of them were na?ves and three non-responders. In all of them, virological response persisted 6 months after discontinuation of therapy, so the sustained virological response rate was 60% in na?ve patients and 30% in non-responders. CONCLUSIONS: Our results suggest that pegylated interferon plus ribavirin combination therapy may be effective in patients with post-liver transplantation recurrent chronic Hepatitis C, even in those previously non-responders to interferon plus ribavirin. These results need to be confirmed by large studies.     

Effect of chenodeoxycholic acid on liver structure and function in man: a stereological and biochemical study

Chenodeoxycholic acid (CDCA) is an effective treatment for dissolving gallstones but experimental studies have suggested that it might be hepatotoxic. The present study is concerned with a group of patients undergoing medical therapy for gallstones for periods of 30 days up to 14 months with CDCA (15 mg/kg/day). Routine functional tests, determination of some liver microsomal enzymes and stereological studies of the liver tissue have been performed and the data have been compared with those obtained before treatment. No significant changes were observed in the functional tests throughout the study. Also the microsomal mixed function oxidase system seemed unaffected by CDCA therapy. The histological features of the liver biopsies were not appreciably different from those observed prior to treatment. Although there were large interindividual variations, the volume density of parenchymal steatosis and of the lipocytes remained comparable in the ssme individual. The ultrastructural features noted in untreated subjects such as curled mitochondrial cristae, slight intracellular bile retention, increased surface density of the rough endoplasmic reticulum were still evident after 14 months of treatment. No additional changes were noted. These results show that no evidence of hepatotoxicity seems to develop in man under therapy with CDCA at the dose considered. But the structural abnormalities observed before treatment appear to persist even in subjects under long-term therapy.     

The fate of electron opaque tracers (horseradish peroxidase and lanthanum chloride) during valproic acid-induced choleresis

ABSTRACT— Horseradish peroxidase (HRP) and lanthanum chloride (LaCl₃) are useful tools for, respectively, the study of vesicular transport through the hepatocyte and the study of the permeability of junctional complexes. These tracers have been used to detect the changes associated with the choleresis independent of bile acids induced by valproic acid (VPA) in rats. The animals were given a single dose of VPA (600 mg/kg, ip). HRP (100 mg/kg) or 5 mM LaCl₃ were given intraportally after 1 h, when bile flow had increased twofold. The excretion of HRP in bile was measured colorimetrically up to 2 h after HRP. Ultrastructural morphometry was conducted on liver of intact rats taken from 1 to 40 min after HRP. The volume density (VD) of HRP-containing vesicles and of HRP-containing multivesicular bodies (MVB) was counted. In VPA-treated rats, HRP appeared in bile with a peak showing at 5 min against 20 min in controls, but the total amount of HRP excreted was less than in controls. The intrahepatocytic vesicular transport of HRP was also modified, showing a peak at 3 min in VPA-treated rats compared to 10 min in controls, together with a decreased VD of pericanalicular vesicles. This was accompanied by an increase of HRP-containing MVB, already evident at 5 min. VPA-induced changes in HRP transport through the hepatocytes appeared twofold: 1) during VPA-induced stimulation of bile flow, there was an early and short-lived increase of transcellular transport and biliary elimination of HRP: 2) a diversion of HRP towards the indirect, lysosomal pathway apparently occurred, in agreement with previous findings concerning the formation of numerous cytolysomes induced by VPA (Hepatology 1984: 4 : 1159–1166). The decreased amount of HRP excreted in bile could be accounted for by a diversion of HRP towards the degradation pathway. The pattern of distribution of LaCl₃ was similar in VPA-treated animals and in controls, suggesting that gross structural alterations of the junctional complexes are unlikely to occur during VPA-induced choleresis.