Diagnostic accuracy of plain computed tomography in detecting acute cerebral venous sinus thrombosis keeping magnetic resonance venography as gold standard.

OBJECTIVE: To determine the diagnostic accuracy of plain computed tomography using the ratio between hounsfield unit and haematocrit of cerebral venous sinuses in cases of acute cerebral venous sinus thrombosis taking magnetic resonance venography as the gold standard. METHODS: The cross-sectional validation study was conducted at the Department of Diagnostic Radiology, Combined Military Hospital, Rawalpindi, Pakistan, from March 9 to September 8, 2021, and comprised patients regardless of age and gender presenting with acute neurological and visual signs and symptoms of cerebral venous sinus thrombosis for <5 days. The patients were brain-imaged on 128-slice computed tomography scanner, and the image was assessed and the attenuation values in terms of Hounsfield unit of dural venous sinuses were calculated by taking appropriate region of interest. Haemoglobin and haematocrit values were noted from blood reports, and then the ratio between Hounsfield unit and haematocrit ratio was calculated. Magnetic resonance venography of the patients were performed and the patients were assessed for dural venous thrombosis. Data was analysed using SPSS 23. RESULTS: Of the 201 patients, 98(48.8%) were males and 103(51.2%) were female. The overall mean age was 35.32±19.707 years (range: 1 month-70 years). According to the Hounsfield unit-haematocrit ratio, acute cerebral venous sinus thrombosis was detected in 173(86.01%) patients, while magnetic resonance venography detected 178(88.6%). The Hounsfield unit-haematocrit ratio had sensitivity 91.01%, specificity 52.17% and diagnostic accuracy 86.57%. CONCLUSIONS: Computed tomography attenuation value and Hounsfield unit-haematocrit ratio on unenhanced computed tomography could be used as a reliable method to detect acute cerebral venous sinus thrombosis in emergency settings.

Prediction of CYP-mediated silybin A-losartan pharmacokinetic interactions using physiological based pharmacokinetic modeling.

The concomitant use of herbal products and synthetic drugs necessitates the assessment of their interaction potentials. The herbal hepatoprotective medicine, silybin A inhibits cytochrome P450 (CYP) 2C9 and 3A4 enzymes, thus, may interact with the drugs that are substrates of CYP2C9 and 3A4, such as losartan. The three most prominent genotypes, expressed by CYP2C9 are the CYP2C9*1/*1, CYP2C9*1/*2 and CYP2C9*1/*3. This study aimed to assess silybin A-losartan interaction in different CYP2C9 genotypes using physiological-based pharmacokinetic (PBPK) model approach. The individual PBPK models for silybin A and losartan were developed using PK-Sim®. Losartan pharmacokinetics was predicted with or without co-administration of silybin A in individuals of different CYP2C9 genotypes to find herbal-drug interaction. The predicted drug plasma curves and pharmacokinetic parameters were optimized using parameter identification tool and were compared with reported pharmacokinetic parameters from the published clinical studies for model validation. The silybin-losartan interactions were predicted by change in area under the curve (AUC) and peak systemic concentration (Cmax). The co-treatment of silybin A, 420 mg/24 h (140 mg/8 h) with losartan 50 mg/24 h, exhibited a genotype-dependent change in the losartan's AUC and Cmax. In CYP 2C9*1/*1 genotype, AUC and Cmax of losartan were increased 1.16 and 1.37 folds, respectively falling in a range stipulated for negligible interaction. Increase in AUC and Cmax by 0.873 and 0.294 folds, respectively in CYP2C9*1/*3 after co-administration of silybin A exhibited a minor interaction with losartan. However, in individuals with CYP2C9*1/*2 genotype, the losartan's AUC and Cmax were decreased by 0.01 folds, manifesting a moderate interaction. Hence, in CYP2C9*1/*1 and CYP2C9*1/*3 genotypes, silybin A is a weak CYP inhibitor for losartan while in CYP2C9*1/*2 genotype, the co-administration of silybin consequents into a moderate pharmacokinetic interaction with losartan.

Pathogenic role of cytokines in COVID-19, its association with contributing co-morbidities and possible therapeutic regimens.

The Covid-19, a threatening pandemic, was originated from China in December 2019 and spread quickly to all over the world. The pathogenesis of coronavirus is linked with the disproportionate response of the immune system. This involves the systemic inflammatory reaction which is characterized by marked pro-inflammatory cytokine release commonly known as cytokine release storm (CRS). The pro inflammatory cytokines are involved in cascade of pulmonary inflammation, hyper coagulation and thrombosis which may be lethal for the individual. That's why, it is very important to have understanding of pro inflammatory cytokines and their pathological role in SARS-CoV-2. The pathogenesis of Covid is not the same in every individual, it can vary due to the presence of pre-existing comorbidities like suffering from already an inflammatory disease such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), chronic obstructive pulmonary disease (COPD), an immune-compromised patients suffering from Diabetes Mellitus (DM) and Tuberculosis (TB) are more vulnerable morbidity and complications following COVID-19. This review is particularly related to COVID-19 patients having comorbidity of other inflammatory diseases. We have discussed the brief pathogenesis of COVID-19 and cytokines release storm with reference to other co-morbidities including RA, IBD, COPD, DM and TB. The available therapeutic regimens for COVID-19 including cytokine inhibitors, anti-viral, anti-biotic, bronchodilators, JAK- inhibitors, immunomodulators and anti-fibrotic agents have also been discussed briefly. Moreover, newly emerging medicines in the clinical trials have also been discussed which are found to be effective in treating Covid-19.

Development and Validation of In-house HEp-2 Cell Slides for Detection of Antinuclear Antibodies (ANA) by Indirect Immunofluorescence.

OBJECTIVE: To develop and validate in-house HEp-2 cell slides for the detection of ANA by indirect immunofluorescence. STUDY DESIGN: Cross sectional validation study. Place and Duration of the Study: Department of Immunology, Armed Forces Institute of Pathology Rawalpindi, Punjab, Pakistan, from April to September 2022. METHODOLOGY: This study involved development of in-house HEp-2 cell slides after procuring cell lines, sub-culturing and fixing them on different slides using variety of fixatives under different protocols. After standardisation of procedure, validation of procedure was done by testing sera of 305 patients for ANA detection at 1:40 dilution on in-house HEp-2 cell slides and subsequently on commercial HEp-2 cell slides (gold standard). Indirect immunofluorescence was observed by the two observers working independently and kept blinded from the results interpreted by each other. Data were collected on a pre-designed proforma and then analysed. Sensitivity, specificity, and positive predictive value (PPV) and negative predictive values (NPV) of in-house HEp-2 cell slides were calculated. RESULT: Sera of 305 patients were tested on in-house and commercial HEp-2 cell slides. Sensitivity and specificity of in-house HEp-2 cell slides for ANA detection were 96.92% and 99.58%, respectively. PPV and NPV of in-house HEp-2 cell slides came out to be 98.43% and 99.17% respectively. CONCLUSION: In-house HEp-2 cell slides are as effective as commercial HEp-2 cell slides for the detection of ANA and can be used as cost-effective alternative. KEY WORDS: Antinuclear antibodies (ANA), Human epithelial type-2 (HEp-2), Immunofluorescence.

Determination of heavy metals (Pb, Cr, As, Hg, and Cd) into the body organs of selected fish, water, sediment, and soil samples from Head Punjnad and Head Taunsa, Punjab, Pakistan.

The present study was conducted on Head Punjnad (HP) and Head Taunsa (HT) to evaluate the contamination of Pb, Cr, As, Hg, and Cd in water, soil, sediment, fish as a whole and fish organs. Fish, water, soil and sediment samples were collected from different sites of HT and HP on a monthly basis for 8 months. Heavy metals in water, soil, and sediment were determined by a polarized Zeeman atomic absorption spectrophotometer and in fish and fish organs by an atomic absorption spectrophotometer. Contamination of Cd, Hg, and As was significantly (P<0.05) higher in water of HP as compared to HT, while Cr showed a non-significant (P>0.05) difference at HP and HT. Pb was significantly (P<0.05) higher in water of HT as compared to HP. In the case of soil, Cd, Hg, and Pb were higher at HT as compared to HP, while As and Cr were significantly (P<0.05) higher at HP as compared to HT. In sediment, contamination of Cd, Hg, and As were significantly (P<0.05) higher at HP as compared to HT, while the Cr difference was non-significant (P>0.05) but Pb showed a significantly (P<0.05) higher value at HT than HP. Cd accumulation in different fish species was recorded as R. rita ˃O. niloticus ˃C. marulius ˃S. sarwari ˃C. idella ˃C. catla ˃N. notopterus ˃E. vacha ˃L. rohita ˃C. carpio, respectively. Hg as O. niloticus ˃S. sarwari ˃R. rita ˃C. marulius ˃C. catla ˃N. notopterus ˃E. vacha ˃L. rohita ˃C. carpio ˃C. idella, respectively. As as O. niloticus ˃R. rita ˃S. sarwari ˃C. marulius ˃C. catla ˃C. carpio ˃N. notopterus ˃C. idella ˃E. vacha ˃L. rohita, respectively. Cr accumulation recorded as L. rohita ˃C. idella ˃O. niloticus ˃C. marulius ˃E. vacha ˃R. rita ˃C. catla ˃C. carpio ˃S. sarwari ˃N. notopterus, respectively. Pb accumulation in different fish species was recorded as C. idella ˃C. carpio ˃N. notopterus ˃L. rohita ˃O. niloticus ˃C. marulius ˃R. rita ˃S. sarwari ˃E. vacha ˃C. catla, respectively. Cd accumulation in different organs was recorded as kidney ˃liver ˃gills ˃muscle ˃skin ˃scale. Hg accumulation in different organs was recorded as kidney ˃gills ˃liver ˃skin ˃muscle ˃scale. As accumulation in different organs was recorded as kidney ˃liver ˃gills ˃muscle ˃skin ˃scale. Cr accumulation in different organs was recorded as gills ˃ liver ˃skin ˃muscle ˃kidney ˃scale. Pb accumulation in different organs was recorded as gills˃ kidney˃ skin˃ liver˃ muscle˃ scale.