Multicomponent synthesis of pyrido[2,3-b]pyrazine derivatives: electrochemical DNA sensing, nonlinear optical properties and biological activity.

We synthesized novel pyrido[2,3-b]pyrazin based heterocyclic compounds (4-7) and their chemical structures were ascertained by spectral techniques (NMR, FT-IR). Besides experimental investigation, density functional theory (DFT) computations with B3LYP/6-31G(d,p) level of theory were executed to obtain spectroscopic and electronic properties. Nonlinear optical (NLO) properties, frontier molecular orbitals (FMOs), UV-visible, vibrational analysis, natural bond orbitals (NBOs), transition density matrix (TDM) and density of states (DOS) analyses of molecules (4-7) were accomplished at B3LYP/6-31G (d,p) level. Global reactivity parameters (GRPs) were correlated with the band gap (Egap) values; compound 7 with lower Egap (3.444 eV), exhibited smaller value of hardness (1.722 eV) with greater softness value (0.290 eV-1). The dipole moment (µ), average polarizability 〈α〉, first (ßtot) and second 〈γ〉 hyper-polarizabilities were calculated for compounds (4-7). Compound 7 showed less Egap, highest absorption wavelength and remarkable NLO response. The highest 〈α〉, ßtot and 〈γ〉 values for compound 7 were observed as 3.90 × 10-23, 15.6 × 10-30 and 6.63 × 10-35 esu, respectively. High NLO response revealed that pyrido[2,3-b]pyrazin based heterocyclic compounds had very remarkable contributions towards NLO technological applications. Further compounds (4-7) are utilized for the first time in electrochemical sensing of DNA, in vitro antioxidant and antiurease activity.

Biogenic Synthesis, Characterization, and In Vitro Biological Evaluation of Silver Nanoparticles Using Cleome brachycarpa.

The therapeutical attributes of silver nanoparticles (Ag-NPs) in both conditions (in vitro and in vivo) have been investigated using different plants. This study focused on the green chemistry approach that was employed to optimize the synthesis of silver nanoparticles (AgNPs) using Cleome brachycarpa aqueous extract as a reducing and stabilizing agent. The characterization of obtained CB-AgNPs was undertaken using UV-visible spectroscopy, Atomic-force microscopy (AFM), Fourier-Transform Infrared Spectroscopy (FTIR), scanning electron microscopy (SEM), and Energy-Dispersive X-ray (EDX) analysis. Results suggest that CB-AgNPs synthesized via stirring produced small-sized particles with more even distribution. The synthesized silver nanoparticles were spherical with a 20 to 80 nm size range. In vitro studies were used to analyze antioxidant, antidiabetic, and cytotoxic potential under different conditions. The results also indicated that CB-AgNPs may have significant potential as an antidiabetic in low concentrations, but also exhibited potential antioxidant activity at different concentrations. Moreover, the anticancer activity against the breast cell line (MCF-7) with IC50 reached up to 18 µg/mL. These results suggest that green synthesized silver nanoparticles provide a promising phytomedicine for the management of diabetes and cancer therapeutics.

The LysR-Type Transcriptional Regulator CrgA Negatively Regulates the Flagellar Master Regulator flhDC in Ralstonia solanacearum GMI1000.

The invasion and colonization of host plants by the destructive pathogen Ralstonia solanacearum rely on its cell motility, which is controlled by multiple factors. Here, we report that the LysR-type transcriptional regulator CrgA (RS_RS16695) represses cell motility in R. solanacearum GMI1000. CrgA possesses common features of a LysR-type transcriptional regulator and contains an N-terminal helix-turn-helix motif as well as a C-terminal LysR substrate-binding domain. Deletion of crgA results in an enhanced swim ring and increased transcription of flhDC In addition, the ΔcrgA mutant possesses more polar flagella than wild-type GMI1000 and exhibits higher expression of the flagellin gene fliC Despite these alterations, the ΔcrgA mutant did not have a detectable growth defect in culture. Yeast one-hybrid and electrophoretic mobility shift assays revealed that CrgA interacts directly with the flhDC promoter. Expressing the ß-glucuronidase (GUS) reporter under the control of the crgA promoter showed that crgA transcription is dependent on cell density. Soil-soaking inoculation with the crgA mutant caused wilt symptoms on tomato (Solanum lycopersicum L. cv. Hong yangli) plants earlier than inoculation with the wild-type GMI1000 but resulted in lower disease severity. We conclude that the R. solanacearum regulator CrgA represses flhDC expression and consequently affects the expression of fliC to modulate cell motility, thereby conditioning disease development in host plants.IMPORTANCERalstonia solanacearum is a widely distributed soilborne plant pathogen that causes bacterial wilt disease on diverse plant species. Motility is a critical virulence attribute of R. solanacearum because it allows this pathogen to efficiently invade and colonize host plants. In R. solanacearum, motility-defective strains are markedly affected in pathogenicity, which is coregulated with multiple virulence factors. In this study, we identified a new LysR-type transcriptional regulator (LTTR), CrgA, that negatively regulates motility. The mutation of the corresponding gene leads to the precocious appearance of wilt symptoms on tomato plants when the pathogen is introduced using soil-soaking inoculation. This study indicates that the regulation of R. solanacearum motility is more complex than previously thought and enhances our understanding of flagellum regulation in R. solanacearum.

Fibrillary Glomerulonephritis in a Patient with Sjogren's Syndrome.

Fibrillary glomerulonephritis (FGN) is an uncommon cause of primary glomerular disease. FGN is usually idiopathic; however, it has been associated with underlying malignancy or autoimmune diseases in some patients as well. The most commonly found autoimmune diseases in FGN patients include Graves' disease, systemic lupus nephritis, Chron's disease, and idiopathic thrombocytopenia purpura. FGN in a patient with underlying asymptomatic Sjogren's syndrome is very rare in the literature, with only two previously reported cases of this association. We present the case of a 75-year-old female with a past medical history of asymptomatic primary Sjogren's syndrome and fibromyalgia, who presented to emergency department with a new episode of hypertension. The electron microscopy (EM) showed randomly arranged nonamyloid fibrillar deposits in the mesangium and glomerular capillary walls, confirming FGN. In this case-based review, we describe in detail the diagnostic work-up, clinical course, and complications in management. We also discuss some of the other nonamyloid fibrillary glomerular diseases.

Adult-onset Minimal Change Disease with IgA Nephropathy and Hepatitis C.

Minimal change disease (MCD) is one of the most common causes of nephrotic syndrome in children, leading to heavy proteinuria and edema. However, it is not as common in adults. Adult-onset minimal change disease with IgA nephropathy is rare. The initial presentation of heavy proteinuria and edema with effacement of podocytes on electron microscopy (EM) should lead the physician to suspect minimal change disease regardless of age. We present a 44-year-old male patient with a history of hepatitis C virus (HCV) who presented with sudden onset of lower extremity edema and 6.6 grams (g) of proteinuria per day.

"Beer Potomania" - A Syndrome of Severe Hyponatremia with Unique Pathophysiology: Case Studies and Literature Review.

Beer potomania, a unique syndrome of hyponatremia, was first reported in 1972. It is described as the excessive intake of alcohol, particularly beer, together with poor dietary solute intake that leads to fatigue, dizziness, and muscular weakness. The low solute content of beer, and suppressive effect of alcohol on proteolysis result in reduced solute delivery to the kidney. The presence of inadequate solute in the kidney eventually causes dilutional hyponatremia secondary to reduced clearance of excess fluid from the body. Early detection of hyponatremia due to beer potomania in the hospital is necessary to carefully manage the patient in order to avoid neurological consequences as this syndrome has unique pathophysiology. We are reporting two cases, presenting to the emergency department with severe hyponatremia. After a detailed initial evaluation of the patients and labs for hyponatremia, a diagnosis of beer potomania was established in both cases. Considering the unique pathophysiology of beer potomania syndrome, the patients were closely monitored and treated appropriately to prevent any neurological sequelae.

COMPARISON OF ANTI-INFLAMMATORY ACTIVITY OF NIGELLA SATIVA AND DICLOFENAC SODIUM IN ALBINO RATS.

BACKGROUND: Nigella sativa or "Kalonji" is a naturally occurring plant in Pakistan and other countries which possesses a wide range of medicinal properties, the anti-inflammatory property being one of these. Diclofenac sodium is a commonly used anti-inflammatory drug. The purpose of this study was to compare the anti-inflammatory effect of ethanolic extract of Nigella sativa seeds with that of diclofenac sodium in albino rats. METHODS: This laboratory randomized controlled trial (RCT) was conducted in the Physiology Department, Services Institute of Medical Sciences (SIMS), Lahore. The study was carried out on 90 male albino rats. Five percent formalin in a dose of 50 µl was injected into sub-plantar surface of right hind paw of each rat to produce inflammation. The rats were randomly divided into three groups of thirty each. Group A was given normal saline (control); group B was given Nigella sativa seed extract; and group C received diclofenac sodium, as a reference drug. Increase in paw diameter, and total and differential leukocyte counts were measured as markers of inflammation. RESULTS: Nigella sativa seeds extract caused significant (p<0.05) reduction in the paw inflammatory response in albino rats. The effect was longer in duration than the effect caused by diclofenac sodium; however, the extract was comparatively less potent than diclofenac sodium. The extract had no significant effect (p>0.05) on the total or differential leukocyte counts. CONCLUSION: Our results suggest that ethanolic extract of Nigella sativa seeds possesses potent anti-inflammatory effect, in albino rats however, this effect is comparatively less but prolonged than that produced by diclofenac sodium.