Antinucleosome antibodies as early predictors of lupus nephritis

Background: The role of the nucleosome in the induction of antibody response in lupus mediated tissue damage especially glomerulonephritis, may provide a new insight in the early diagnosis and alternative therapeutic developments in systemic lupus erythematosus (SLE). Objectives: To evaluate the frequency and specificity of antinucleosome antibody expression in SLE patients in relation to disease activity. Also, to assess their predictive value in subclinical lupus nephritis. Methods: This study included 26 patients with SLE and 52 control subjects (26 were healthy and 26 had juvenile rheumatoid arthritis "JRA"). Among lupus patients, 15 had clinical evidence of renal involvement. After clinical evaluation to calculate the SLE disease activity index (SLEDAI), measurements of urinary microalbumin and serum antinucleosome antibodies (antinucleosome specific, antihistone and anti ds-DNA antibodies by ELISA) were performed. Patients without clinical evidence of renal involvement were followed up for one year and measurement of urinary microalbumin was repeated at the end of the study period. Those who later developed microalbuminurea were categorized as patients with subclinical lupus nephritis. Results: The expression of the 3 studied antinucleosome antibodies was significantly higher among lupus patients as compared to JRA patients and healthy controls. Seropositivity for one or more antinucleosome antibodies was elicited in 84.5% of lupus patients. Serum levels of the 3 antinucleosome antibodies were significantly higher among lupus patients with clinical nephritis than those without nephritis. ANSAb had higher sensitivity, specificity and positive and negative predictive values for subclinical lupus nephritis (100%) than antihistone and anti ds-DNA antibodies (43%, 100%, 100% and 50% respectively for either antibodies). All patients with lupus nephritis were seropositive for at least one of the antinucleosome antibodies, while those without clinical or subclinical nephritis were seronegative for the 3 antinucleosome antibodies. In 27.3% of patients with lupus nephritis, ANSAB was positive while both antihistone and ds-DNA antibodies were negative. Antinucleosome antibodies correlated positively with SLEDAI and cumulative steroid dose and negatively with corrected creatinine clearance. Conclusions: The observed sensitivity and specificity of antinucleosome specific antibodies as early indicators of subclinical lupus nephritis appear encouraging and deserve further analysis on a large scale in order to confirm their validity, especially in the anti ds-DNA seronegative lupus patients.Keywords: antinucleosome antibodies, antinucleosome specific antibodies, anti ds-DNA antibodies, antihistone antibodies, SLE, lupus nephritisEgypt J Pediatr Allergy Immunol 2005; 3(2):54-6

Taxifolin prevents cisplatin nephrotoxicity by modulating Nrf2/HO-1 pathway and mitigating oxidative stress and inflammation in mice

Cisplatin (CIS) is an effective chemotherapeutic agent used in the treatment of several malignancies. The clinical use of CIS is associated with adverse effects, including acute kidney injury (AKI). Oxidative stress and inflammation are key events in the development of CIS-induced AKI. This study investigated the protective effect of taxifolin (TAX), a bioactive flavonoid with promising health-promoting properties, on CIS-induced nephrotoxicity in mice. TAX was orally given to mice for 10 days and a single dose of CIS was injected at day 7. Serum blood urea nitrogen (BUN) and creatinine were elevated, and multiple histopathological alterations were observed in the kidney of CIS-administered mice. CIS increased renal malondialdehyde (MDA), nitric oxide (NO), nuclear factor-kappaB (NF-κB) p65, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β, and decreased cellular antioxidants in mice. TAX remarkably prevented kidney injury, ameliorated serum BUN and creatinine, and renal MDA, NO, NF-κB p65, and pro-inflammatory cytokines, and boosted antioxidant defenses in CIS-administered mice. TAX downregulated Bax and caspase-3, and upregulated Bcl-2. These effects were associated with upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) expression and heme oxygenase (HO)-1 activity in CIS-administered mice. In conclusion, TAX prevented CIS-induced AKI by mitigating tissue injury, oxidative stress, inflammation, and cell death. The protective efficacy of TAX was associated with the upregulation of Nrf2/HO-1 signaling

Novel spectrophotometric method for determination of cinacalcet hydrochloride in its tablets via derivatization with 1,2-naphthoquinone-4-sulphonate

This study represents the first report on the development of a novel spectrophotometric method for determination of cinacalcet hydrochloride (CIN) in its tablet dosage forms. Studies were carried out to investigate the reaction between CIN and 1,2-naphthoquinone-4-sulphonate (NQS) reagent. In alkaline medium (pH 8.5), an orange red-colored product exhibiting maximum absorption peak (λmax) at 490 nm was produced. The stoichiometry and kinetic of the reaction were investigated and the reaction mechanism was postulated. This color-developing reaction was employed in the development of a simple and rapid visible-spectrophotometric method for determination of CIN in its tablets. Under the optimized reaction conditions, Beer's law correlating the absorbance with CIN concentration was obeyed in the range of 3 - 100 μg/ml with good correlation coefficient (0.9993). The molar absorptivity (ε) was 4.2 × 105 l/mol/cm. The limits of detection and quantification were 1.9 and 5.7 μg/ml, respectively. The precision of the method was satisfactory; the values of relative standard deviations (RSD) did not exceed 2%. No interference was observed from the excipients that are present in the tablets. The proposed method was applied successfully for the determination of CIN in its pharmaceutical tablets with good accuracy and precisions; the label claim percentage was 100.80 - 102.23 ± 1.27 - 1.62%. The results were compared favorably with those of a reference pre-validated method. The method is practical and valuable in terms of its routine application in quality control laboratories

Threat of antimicrobial resistance among pilgrims with infectious diseases during Hajj : lessons learnt from COVID-19 pandemic

Hajj pilgrimage is a large mass gathering global event that may facilitate the spread and emergence of various infectious diseases as well as antimicrobial resistance (AMR) in a local and global scenario. Planning and preparing for these public health issues is a challenging and complex process for the Kingdom of Saudi Arabia (KSA) health authorities. Despite multiple efforts for the prevention and treatment of infectious diseases through longtime funding in education and medical care, the prevalence of infectious disease is still high among Hajj pilgrims. The commonly observed infectious diseases during Hajj include respiratory tract infections (influenza and pneumonia), urinary tract infections and skin infections that may necessitate the use of antimicrobials. Beta-lactams are used as a first-line treatment for hospital acquired infections as well as community acquired infections due to their broad-spectrum activity. However, most of the bacterial isolates such as Staphylococcus spp., Pseudomonas spp. and E. coli are resistant to beta-lactams. Irrational use of anti-microbials, lack of infection prevention practices and suboptimal healthcare access further exacerbate the risk of spreading AMR among Hajj pilgrims. Enhanced collaboration between countries, sharing of best practices and international cooperation are crucial in addressing AMR threats among pilgrims. Consequently, robust surveillance systems for early detection and monitoring of AMR, collaboration with national as well as international healthcare agencies, effective infection prevention and control measures, public awareness, and rational use of antimicrobials via antimicrobial stewardship programs are required to mitigate the risk of AMR and ensure the health and well-being of pilgrims during Hajj

Role of L- glutamine and crizanlizumab in sickle cell anaemia painful crisis reduction

BackgroundPatients with sickle cell disease, frequently ‎ suffer from intense painful episodes. Till recently hydroxyurea was the only available medical therapy that approved for reduction of painful episodes.AimsTo summarize the available data from randomized controlled trials that aim to evaluate the efficacy of newly approved L-‎glutamine‎ (alters redox state of red blood cells ‎‎[RBCs]) ‎and ‎crizanlizumab (‎(anti-P-selectin)‎)‎ ‎on vaso-occlusive episodes in Sickle cell disease ‎ patients.Methods PubMed, ‎Google Scholar, and EBSCO ‎ databases were ‎‎systematically search for relevant articles. The terms ‎ ‎ ‎ L-glutamine, sickle cell disease, sickle cell ‎anaemia,‎ ‎‎crizanlizumab ‎and vaso-occlusive episodes‎ were used.Results Out of Four-hundred seventy-two records, only three fulfilled the inclusion criteria. Two trials were aimed to evaluate the efficacy of L-glutamine therapy on the frequency of painful crises in sickle cell anaemia patients. Both studies showed that L-glutamine therapy significantly reduce the frequency of VOEs. Only one trial examined the ability of crizanlizumab on VOEs reduction, and showed crizanlizumab successful reduce the occurrence of VOEs.‎ConclusionNewer agent ‎with different mechanism of action, such as ‎L-glutamine, ‎and crizanlizumab may consider if ‎hydroxyurea not effective or not ‎tolerable

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century