Efficacy and superiority of an innovative method (IM) of intravenous (IV) fluid drip drop rate calculation using IV set and its comparison with conventional methods (CM)

Background: Almost every indoor patient requires some form of intravenous (IV) fluids and its infusion rate should be proper as recommended for best treatment outcomes. To overcome the same, a simple, quick and easily applicable new method for drip drop rate calculation is proposed, which is user-friendly at bedside and doesn’t require mathematical skills or help.Methods: Author compared this novel innovative method (IM) of IV fluid drip drop rate method for both regular macro and micro drop infusion set against conventional mathematical calculation method (MC) of infusion in various IV fluid indoor orders and assessed for time-to-initiation of treatment (TI) required and its accuracy. Ten resident doctors and ten nursing staff participated to grade both conventional and novel methods by using pre-printed forms of various parameters like time consumption, comfort level, accuracy and applicability in ward and these both methods were scored on a scale of 1 to 10.Results: Conventional method (CM) required 14.23±1.10seconds, while novel method (IM) required average 3.63±0.73seconds for calculation of drop rate. Average grading for conventional method was 3.63±0.49 and for novel method was 7.84±0.6 out of 10.Conclusions: Novel method of IV fluid drip drop rate formula is easy, quick and superior in comparison to conventional method and it doesn’t require any additional instrumental help. It is good alternative to conventional formula for IV drip drop rate calculation in absence of infusion pump

Urinary Tract Infection in Renal Allograft Recipents

Renal replacement therapy in the form of renal transplantation (RT) is the treatment of choice in these patients. Various factors influence the graft survival, infections being most common. Infections account for 16% of patient deaths and 7.7% of death censored graft failure in renal transplant patients. Urinary tract infection (UTI) is the most common infectious complication accounting for 45–72% of all infections. According to few studies UTI may have a negative impact over the long term survival of renal allograft. There are multiple factors that predispose these patients to UTI. Elderly age group, female gender, increased duration of catheterization and anatomical abnormalities of the urinary tract are most common predisposing factors. E. coli is the most frequently isolated organisms from the urine of these patients. We would proceed further with two cases which presented as UTI in post-transplant period. The first patient transplanted (living donor related) for diabetes induced end stage renal disease had developed UTI 4 years post-transplant. The other patient underwent deceased donor renal transplant for adult polycystic disease related chronic kidney disease, presented 2 years post-transplant with UTI

Pathology Associated with Hormones of Adrenal Cortex

Adrenal gland is an endocrine organ comprising of an outer cortex and inner medulla. These secrete various hormones that have a vital role in maintaining the normal homeostasis of the body. Lesions of adrenal cortex are quite common to encounter and most of these are related to the hormones secreted by three layers of adrenal cortex: the zona glomerulosa, the zona fasciculata, and the zona reticularis. Also it is very infrequent to encounter metastatic lesions in the adrenal glands too. So it is very important as a part of a clinician as well as a pathologist to know the pattern in which these hormones are secreted along with their physiological roles. Thus this chapter includes the disease that are related to excess as well as deficiencies of the hormones secreted by adrenal cortex. The chapter also includes various genetic syndromes that are associated with the disorders associated with hormones of adrenal cortex. The last part of the chapter includes a brief description of various benign as well as malignant lesions, the pathological as well as the etiological aspects and the hormonal abnormalities associated. This chapter thus mainly focuses on the pathology associated with the adrenal cortex and hormones secreted by the various layers of adrenal cortex

Mitochondrial Cytopathies of the Renal System

Mitochondria are major intracellular organelles with a variety of critical roles like adenosine triphosphate production, metabolic modulation, generation of reactive oxygen species, maintenance of intracellular calcium homeostasis, and the regulation of apoptosis. Mitochondria often undergo transformation in both physiological and pathological conditions. New concepts point that mitochondrial shape and structure are intimately linked with their function in the kidneys and diseases related to mitochondrial dysfunction have been identified. Diseases associated with mitochondrial dysfunction are termed as “mitochondrial cytopathies”. Evidence support that there is a role of mitochondrial dysfunction in the pathogenesis of two common pathways of end-stage kidney disease, namely, chronic kidney disease (CKD) and acute kidney injury (AKI). Mitochondrial cytopathies in kidneys mainly manifest as focal segmental glomerular sclerosis, tubular defects, and as cystic kidney diseases. The defects implicated are mutations in mtDNA and nDNA. The proximal tubular cells are relatively vulnerable to oxidative stress and are therefore apt to suffer from respiratory chain defects and manifest as either loss of electrolyte or low-molecular-weight proteins. Patients with mitochondrial tubulopathy are usually accompanied by myoclonic epilepsy and ragged red muscle fibers (MERRF), and Pearson’s, Kearns-Sayre, and Leigh syndromes. The majority of genetic mutations detected in these diseases are fragment deletions of mtDNA. Studies have shown significantly increased ROS production, upregulation of COX I and IV expressions, and inactivation of complex IV in peripheral blood mononuclear cells of patients with stage IV–V CKD, thereby demonstrating the close association between mitochondrial dysfunction and progression to CKD. Furthermore, the mechanisms that translate cellular cues and demands into mitochondrial remodeling and cellular damage, including the role of microRNAs and lncRNAs, are examined with the final goal of identifying mitochondrial targets to improve treatment of patients with chronic kidney diseases

Interaction of Pyrrolobenzodiazepine (PBD) Ligands with Parallel Intermolecular G-Quadruplex Complex Using Spectroscopy and ESI-MS

Studies on ligand interaction with quadruplex DNA, and their role in stabilizing the complex at concentration prevailing under physiological condition, has attained high interest. Electrospray ionization mass spectrometry (ESI-MS) and spectroscopic studies in solution were used to evaluate the interaction of PBD and TMPyP4 ligands, stoichiometry and selectivity to G-quadruplex DNA. Two synthetic ligands from PBD family, namely pyrene-linked pyrrolo[2,1-c][1,4]benzodiazepine hybrid (PBD1), mixed imine-amide pyrrolobenzodiazepine dimer (PBD2) and 5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrin (TMPyP4) were studied. G-rich single-stranded oligonucleotide d(5′GGGGTTGGGG3′) designated as d(T2G8), from the telomeric region of Tetrahymena Glaucoma, was considered for the interaction with ligands. ESI-MS and spectroscopic methods viz., circular dichroism (CD), UV-Visible, and fluorescence were employed to investigate the G-quadruplex structures formed by d(T2G8) sequence and its interaction with PBD and TMPyP4 ligands. From ESI-MS spectra, it is evident that the majority of quadruplexes exist as d(T2G8)2 and d(T2G8)4 forms possessing two to ten cations in the centre, thereby stabilizing the complex. CD band of PBD1 and PBD2 showed hypo and hyperchromicity, on interaction with quadruplex DNA, indicating unfolding and stabilization of quadruplex DNA complex, respectively. UV-Visible and fluorescence experiments suggest that PBD1 bind externally where as PBD2 intercalate moderately and bind externally to G-quadruplex DNA. Further, melting experiments using SYBR Green indicate that PBD1 unfolds and PBD2 stabilizes the G-quadruplex complex. ITC experiments using d(T2G8) quadruplex with PBD ligands reveal that PBD1 and PBD2 prefer external/loop binding and external/intercalative binding to quadruplex DNA, respectively. From experimental results it is clear that the interaction of PBD2 and TMPyP4 impart higher stability to the quadruplex complex

Assay strategies for the discovery and validation of therapeutics targeting <i>Brugia pahangi</i> Hsp90

The chemotherapy of lymphatic filariasis relies upon drugs such as diethylcarbamazine and ivermectin that largely target the microfilarial stages of the parasite, necessitating continued treatment over the long reproductive life span of the adult worm. The identification of compounds that target adult worms has been a long-term goal of WHO. Here we describe a fluorescence polarization assay for the identification of compounds that target Hsp90 in adult filarial worms. The assay was originally developed to identify inhibitors of Hsp90 in tumor cells, and relies upon the ability of small molecules to inhibit the binding of fluorescently labelled geldanamycin to Hsp90. We demonstrate that the assay works well with soluble extracts of Brugia, while extracts of the free-living nematode C. elegans fail to bind the probe, in agreement with data from other experiments. The assay was validated using known inhibitors of Hsp90 that compete with geldanamycin for binding to Hsp90, including members of the synthetic purine-scaffold series of compounds. The efficacy of some of these compounds against adult worms was confirmed in vitro. Moreover, the assay is sufficiently sensitive to differentiate between binding of purine-scaffold compounds to human and Brugia Hsp90. The assay is suitable for high-throughput screening and provides the first example of a format with the potential to identify novel inhibitors of Hsp90 in filarial worms and in other parasitic species where Hsp90 may be a target

Measurement of the Branching Ratios for the Decays of Ds+→ηπ+,η′π+,ηρ+D_{s}^{+}\to \eta\pi^{+}, \eta^{'}\pi^{+}, \eta\rho^{+}, and eta′ρ+eta^{'}\rho^{+}

Using a data sample with integrated luminosity of about 3.9 fb^{-1} collected in e+ e- annihilation with the CLEO-II detector at the Cornell Electron Storage Ring, we have measured the branching ratios for the decay modes Ds -> (eta, eta') pi and Ds -> (eta, eta') rho relative to Ds -> phi pi. These decay modes are among the most common hadronic decays of the Ds's and can be related by factorization to the semileptonic decays Ds -> (eta,eta') l nu. The results obtained are compared with previous CLEO results and with the branching ratios measured for the related semileptonic decays. We also report results on the Cabibbo-suppressed decays of the D+ to the same final states.Comment: 18 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN