Profiling of inflammatory biomarkers in mild to critically ill severe acute respiratory syndrome corona virus-19 (SARS Covid-19) patients from Karachi, Pakistan.

SARS-Covid-19 infection got spread in many countries and WHO declared it as a serious global Pandemic. Pro-inflammatory cytokines storm generated by Covid-19 infection hyper-activates inflammatory response in host body, resulting in elevated release of inflammatory biomarkers. Present article describes the characteristic profile of these inflammatory and related biomarkers in a total of 48 critically ill Covid-19 patients, (Male = 38, F = 10), with mildly ill to severe, critically ill status and thus grouped accordingly. Inflammatory Biomarkers, Ferritin, ProCalcitonin, C-Reactive Protein, coagulation marker-D-Dimer, chemical analytes, Protein, Albumin, BUN, Bilirubin, Creatinine, and enzymes, Lactate Dehydrogenase, γ-Glutamyl transpeptidases, Alkaline phosphatase were routine analyzed by standard methods described earlier. D-dimer, Ferritin, CRP and Procalcitonin exhibited variable alterations (P<0.05 to P<0.001), more markedly in critically ill patients than in the mild and severe. Biochemical analytes and enzymatic parameters showed elevated levels (P<0.05 to P<0.01) mostly in critically ill category of patients when compared with mild or severe, except total protein and albumin, which remained non-significant. It is concluded that cytokine, chemokines and pro-inflammatory markers, which released in abnormally high concentrations in Covid-19 patients of variable syndrome intensity, are significant indicators of disease severity, progression and success of treatments. As the pharmacological options may vary with the different stages of the disease therefore identifying the correct stage of the disease may be very useful in selecting the best option.

REPORT- Varying pattern of blood gases, ferritin, procalcitonin, C-Reactive protein, interleukin 6 and lactate dehydrogenase in Covid-19 patients suffering from diverse Co-Morbid, suspected cytokine storm and periodic effects of antiviral and steroidal treatments.

This study depicted varying pattern of inflammatory markers and blood gases of selected SARS Covid-19 patients with triggered cytokine storm, during their stay in ICUs, HDUs, on ventilators for 21 days. All were treated with Antiviral (remdesivir), steroid (dexamethason) and antipyretic (paracetamol) medications. Procalcitonin, PCT, C-reactive protein CRP, Interleukin 6 (IL6) and Lactate dehydrogenase (LDH) blood gases pressure (pO2, pCO2), coagulation (D-Dimer DD) and Iron storage proteins (Ferritin Ft) were analyzed by fully automated analyzers. All biomarkers of each patient category was statistically compared with days 1st, 4th, 7th versus 10th, 14th and 17th days and reported as significant where p<0.05, to assess progression, worsening or recovery status. IL6 (P<0.0224, P< 0.0228) and CRP (P<0.0277) exhibited none or mild statistical significance difference, with the exception of Ferritin (P<0.0185; P<0.0088) and D Dimer (P<0.0086), demonstrating slow recovery, revealing stronger cytokine storming assault. LDH, pCO2 and pO2 exhibited variable significance difference when data of earlier days were compared with recovery phase, thus advocating blended treatment or progressing of disease. Analysis confirms overwhelming pathogenesis of SARS Covid-19 distinctive cytokine storm, which needed to be cautiously monitored as infection progressed using pro-inflammatory biomarkers as indicators of recovery or worsening of the disease.

Role of ALAD and VDR genotypes on the association of low blood lead level with serum uric acid and blood pressure in automobile paint workers of Karachi, Pakistan.

Lead is an environmental pollutant having nephrotoxic effects even at low level. Its continuous exposure is associated with increased serum uric acid level that resulting in renal insufficiency. This research was conducted to see the effects of delta-aminolevulinic acid dehydratase (ALAD) and vitamin D receptor (VDR) genotypes on biochemical parameters and blood pressure (BP) of automobile workers having low blood lead level (BLL) with continuous lead exposure. Automobile paints workers with ALAD 1-2 genotype showed the positive association of BLL with diastolic BP (p<0.05) whereas, a genotypic combination of ALAD 1-2/VDR BB showed the negative association of serum uric acid with BLL (p<0.05). Similarly negative effects of VDR BB genotype (p<0.01) and ALAD 1-2 genotype (p<0.05) were observed in the association of serum uric acid with BLL at the mean age ≥30 years. This suggests that automobile paint workers having ALAD 1-2 genotypes are at the risk of increased diastolic BP. The research also foretells that combination of ALAD 1-2/VDR BB may play a significant role against lead induced nephrotoxicity at low BLL with continuous lead exposure.

Loop 1 of transducer region in mammalian class I myosin, Myo1b, modulates actin affinity, ATPase activity, and nucleotide access.

Loop 1, a flexible surface loop in the myosin motor domain, comprises in part the transducer region that lies near the nucleotide-binding site and is proposed from structural studies to be responsible for the kinetic tuning of product release following ATP hydrolysis (1). Biochemical studies have shown that loop 1 affects the affinity of actin-myosin-II for ADP, motility and the V(max) of the actin-activated Mg2+-ATPase activity, possibly through P(i) release (2-8). To test the influence of loop 1 on the mammalian class I myosin, Myo1b, chimeric molecules in which (i) loop 1 of a truncated form of Myo1b, Myo1b1IQ, was replaced with either loop 1 from other myosins; (ii) loop 1 was replaced with glycine; or (iii) some amino acids in the loop were substituted with alanine and were expressed in baculovirus, and their interactions with actin and nucleotide were evaluated. The steady-state actin-activated ATPase activity; rate of ATP-induced dissociation of actin from Myo1b1IQ; rate of ADP release from actin-Myo1b1IQ; and the affinity of actin for Myo1b1IQ and Myo1b1IQ.ADP differed in the chimeras versus wild type, indicating that loop 1 has a much wider range of effects on the coupling between actin and nucleotide binding events than previously thought. In particular, the biphasic ATP-induced dissociation of actin from actin-Myo1b1IQ was significantly altered in the chimeras. This provided evidence that loop 1 contributes to the accessibility of the nucleotide pocket and is involved in the integration of information from the actin-, nucleotide-, gamma-P(i)-, and calmodulin-binding sites and predicts that loop 1 modulates the load dependence of the motor.