Virus-induced cytokines regulate circulating lymphocyte levels during primary SIV infections

Decline in blood CD4+ lymphocytes during primary symptomatic infections with HIV is usually attributed to viral killing, and has not been considered in terms of altered lymphocyte migration and sequestration. We therefore sought to examine whether CD4+ cell loss from blood of macaques undergoing an acute primary SIV infection might be due to increased synthesis of cytokines, known to profoundly affect lymphocyte trafficking, rather than to direct lymphocyte destruction by virus. The findings indicate that rapid lymphocyte depletion following acute infection is not selective for CD4+ cells, correlates precisely with increased plasma IFN-gamma and tumor necrosis factor-alpha levels, and is reversible. CD4/CD8 ratios in lymph nodes with high viral burdens remain relatively unchanged despite lymphocyte loss from blood. Levels of cytokine mRNA measured in lymphoid organs reflect neither cytokine plasma levels nor their potential to induce sequestration. These results support a model of cytokine-induced lymphocyte extravasation to account for the acute HIV/SIV-induced CD4+ cell lymphopenia and raise questions regarding the extent to which altered lymphocyte migration plays a role in the gradual CD4+ cell depletion throughout infection.      

Emerging COVID-19 variants and their impact on SARS-CoV-2 diagnosis,therapeutics and vaccines

The emergence of novel and evolving variants of SARS-CoV-2 has fostered the need for change in the form of newer and more adaptive diagnostic methods for the detection of SARS-CoV-2 infections. On the other hand, developing rapid and sensitive diagnostic technologies is now more challenging due to emerging variants and varying symptoms exhibited among the infected individuals. In addition to this, vaccines remain the major mainstay of prevention and protection against infection. Novel vaccines and drugs are constantly being developed to unleash an immune response for the robust targeting of SARS-CoV-2 and its associated variants. In this review, we provide an updated perspective on the current challenges posed by the emergence of novel SARS-CoV-2 mutants/variants and the evolution of diagnostic techniques to enable their detection. In addition, we also discuss the development, formulation, working mechanisms, advantages, and drawbacks of some of the most used vaccines/therapeutic drugs and their subsequent immunological impact.

Key message

• The emergence of novel variants of the SARS-CoV-2 in the past couple of months, highlights one of the primary challenges in the diagnostics, treatment, as well as vaccine development against the virus.
• Advancements in SARS-CoV-2 detection include nucleic acid based, antigen and immuno- assay-based and antibody-based detection methodologies for efficient, robust, and quick testing; while advancements in COVID-19 preventive and therapeutic strategies include novel antiviral and immunomodulatory drugs and SARS-CoV-2 targeted vaccines.
• The varied COVID-19 vaccine platforms and the immune responses induced by each one of them as well as their ability to battle post-vaccination infections have all been discussed in this review.

     

Trinucleotide expansion mutations in the cartilage oligomeric matrix protein (COMP) gene

Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are two human autosomal dominant skeletal dysplasias characterized by variable short stature, joint laxity and early-onset degenerative joint disease. Both disorders can result from mut-ations in the gene for cartilage oligomeric matrix protein (COMP), an extracellular matrix glycoprotein. About one-third of PSACH cases result from heterozygosity for deletion of one codon within a very short triplet repeat, (GAC)5, which encodes five consecutive aspartic acid residues within the calmodulin-like region of the COMP protein. We have identified two expansion mut-ations in this repeat: an MED patient carrying a (GAC)6allele and a PSACH patient carrying a (GAC)7allele. These are among the shortest disease-causing triplet repeat expansion mutations described thus far, and are the first identified in a GAC repeat. A unique feature of this sequence is that expansion as well as shortening of the repeat can cause the same disease. In cartilage, both patients have rough endoplasmic reticulum inclusions in chondrocytes. The inclusions are also present in tendon tissue and can be reproduced in cultured tendon cells, suggesting that the pathophysiology of disease is similar in both cartilage and tendon.      

Normal and occluded mediastinal veins: MR imaging

The potential of magnetic resonance (MR) imaging to demonstrate the mediastinal veins was evaluated retrospectively in 25 patients with no evidence of a venous abnormality, 28 patients who had narrowing or occlusion of a mediastinal vein, and two patients who had a venous anomaly. In patients with venous occlusion, the MR images graphically demonstrated the sites and extent. MR images also demonstrated slow flow within venous structures proximal to the obstruction. Generally, venous collaterals in the mediastinum and chest wall were better seen with contrast material-enhanced computed tomography scans. The marked contrast on MR images between the signal void of normal vascular structures, the moderate signal intensity of tumor, and the high signal intensity of a thrombus or slowly flowing blood allows ready detection of venous occlusion and may suggest the nature of the occlusion.     

Pulmonary nodules: detection using magnetic resonance and computed tomography

Detection of pulmonary nodules using spin-echo magnetic resonance (MR) imaging was compared with detection using computed tomography (CT). Of the 25 patients studied independently by two radiologists, no lung nodules were detected in 11 (CT or MR), ten had a single nodule, and four had multiple nodules. The lesions not seen using CT or MR were less than 1.3 cm in diameter. The greater spatial resolution of CT enabled better detection of nodules close to the diaphragm, the pleura, or to each other, whereas the better contrast resolution of MR enabled the detection of several nodules close to blood vessels. With MR, nodules were best seen on images with long repetition times (2.0 sec). Most pulmonary nodules are seen using both CT and MR. CT generally enables the detection of more small nodules than MR does, and some low-density nodules near blood vessels are better displayed using MR.     

A new pyeloureteral drainage catheter

We describe a new pyeloureteral drainage catheter that can be used for both genitourinary tract stenting and drainage, as well as tamponade of bleeding from the renal parenchyma or subcutaneous tissue. Primary indications for the use of this catheter and recommendations on insertion techniques are presented. With the exception of one case of minor kinking of the catheter, we have had no complications or failures with this catheter. While insertion through an unprotected tissue track is somewhat difficult, we have had good success introducing the catheter through a 24-F or larger Teflon working sheath. The catheter has excellent patient retention properties. It can be converted from external to internal drainage or vice versa simply and quickly on the ward.     

Glutamine-enriched enteral nutrition in very low birth weight infants. Design of a double-blind randomised controlled trial [ISRCTN73254583]

Background

Enteral feeding of very low birth weight (VLBW) infants is a challenge, since metabolic demands are high and administration of enteral nutrition is limited by immaturity of the gastrointestinal tract. The amino acid glutamine plays an important role in maintaining functional integrity of the gut. In addition, glutamine is utilised at a high rate by cells of the immune system. In critically ill patients, glutamine is considered a conditionally essential amino acid. VLBW infants may be especially susceptible to glutamine depletion as nutritional supply of glutamine is limited in the first weeks after birth. Glutamine depletion has negative effects on functional integrity of the gut and leads to immunosuppression. This double-blind randomised controlled trial is designed to investigate the effect of glutamine-enriched enteral nutrition on feeding tolerance, infectious morbidity and short-term outcome in VLBW infants. Furthermore, an attempt is made to elucidate the role of glutamine in postnatal adaptation of the gut and modulation of the immune response.

Methods

VLBW infants (gestational age <32 weeks and/or birth weight <1500 g) are randomly allocated to receive enteral glutamine supplementation (0.3 g/kg/day) or isonitrogenous placebo supplementation between day 3 and 30 of life. Primary outcome is time to full enteral feeding (defined as a feeding volume ≥ 120 mL/kg/day). Furthermore, incidence of serious infections and short-term outcome are evaluated. The effect of glutamine on postnatal adaptation of the gut is investigated by measuring intestinal permeability and determining faecal microflora. The role of glutamine in modulation of the immune response is investigated by determining plasma Th1/Th2 cytokine concentrations following in vitro whole blood stimulation.