Imaging spectrum of renal masses on multi-slice computed tomography

Background: Multi-slice computed tomography (MSCT) is the mainstay for preoperative assessment of many complex renal masses in current clinical practice. Benign renal processes may simulate malignant renal tumors and could be defined correctly by CT. MSCT has also an important role in tumor staging. The purpose of this article is to understand the imaging spectrum of renal masses on MSCT and assess the usefulness of CT in surgical planning and management.Methods: Studied 500 patients with suspected renal lesions who underwent MSCT during the period July 2017 to July 2020 at state-of-art imaging center. CT imaging was done in those patients in whom clinical examination and ultrasonography (USG) revealed possibility of diagnosis of renal masses for further detailed evaluation and deciding management.Results: Out of 500 total subjects, the common age group in this study is 51 to 60 years (25%). Male preponderance (59%) was noted. The most common presentation was pain (84%) followed by lump (29.4%) and haematuria (17.8%). Malignant masses (51%) were more common followed by benign (39%) and inflammatory masses (10%) respectively. Renal cell carcinoma has more incidence (30%) followed by simple cyst (20%). Calcification (19.6%), perinephric extension (78%) and vascular invasion (21.5%) are more common in malignant masses. Conclusion: MSCT is the modality of choice for the diagnosis of renal masses and deciding management approach in current practice. Detection of tumoral spread, invasion of surrounding organs and vascular structure are better with CT. MSCT also has a role in postoperative follow-up of renal masses

Pharmacokinetics, safety, and efficacy of a single co-administered dose of diethylcarbamazine, albendazole and ivermectin in adults with and without Wuchereria bancrofti infection in Cote d\u27Ivoire

BackgroundA single co-administered dose of ivermectin (IVM) plus diethylcarbamazine (DEC) plus albendazole (ALB), or triple-drug therapy, was recently found to be more effective for clearing microfilariae (Mf) than standard DEC plus ALB currently used for mass drug administration programs for lymphatic filariasis (LF) outside of sub-Saharan Africa. Triple-drug therapy has not been previously tested in LF-uninfected individuals from Africa. This study evaluated the pharmacokinetics (PK), safety, and efficacy of triple-drug therapy in people with and without Wuchereria bancrofti infection in West Africa.MethodsIn this open-label cohort study, treatment-naïve microfilaremic (>50 mf/mL, n = 32) and uninfected (circulating filarial antigen negative, n = 24) adults residing in Agboville district, Côte d’Ivoire, were treated with a single dose of IVM plus DEC plus ALB, and evaluated for adverse events (AEs) until 7 days post treatment. Drug levels were assessed by liquid chromatography and mass spectrometry. Persons responsible for assessing AEs were blinded to participants’ infection status.FindingsThere was no difference in AUC0-inf or Cmax between LF-infected and uninfected participants (P>0.05 for all comparisons). All subjects experienced mild AEs; 28% and 25% of infected and uninfected participants experienced grade 2 AEs, respectively. There were no severe or serious adverse events. Only fever (16 of 32 versus 4 of 24, PConclusionsModerate to heavy W. bancrofti infection did not affect PK parameters for IVM, DEC or ALB following a single co-administered dose of these drugs compared to uninfected individuals. The drugs were well tolerated. This study confirmed the efficacy of the triple-drug therapy for clearing W. bancrofti Mf and has added important information to support the use of this regimen in LF elimination programs in areas of Africa without co-endemic onchocerciasis or loiasis.Trial registrationClinicalTrials.gov NCT02845713.</div

MSCT coronary angiography in non-invasive assessment of coronary artery bypass grafts patency

Background: Coronary artery disease (CAD) is one of the leading cause of the morbidity and mortality in India and worldwide and last decade has seen a steep rise in incidence of CAD in India and its treatment as bypass surgery. Direct visualization of the grafts and native coronary arteries by invasive catheterization is now being replaced by non-invasive CT coronary angiography with higher slice machines and newer technology as it has good temporal resolution, high scanning speed as well as low radiation dose. We share our experience of graft imaging on 128 slice CT machine.Methods: This is a retrospective, single-center, observational study. We included 500 symptomatic patients who have undergone CT study between the year 2014 to 2018 post bypass surgery.Results: Arterial grafts have a better patency rate than venous grafts. (88% vs. 64.1%). Amongst the individual arterial grafts RIMA had the best patency rate (100%) followed by LIMA (90.8%), RA (68.7%). LAD was the most commonly involved artery (91%).Conclusions: Significant absolute concordance between CT and catheter angiographic findings have been documented for all arterial and venous grafts patency in the literature. The MSCT with retrospective gating permits an accurate and non-invasive evaluation of patent and diseased arterial and vein grafts and could replace conventional angiography for the follow-up of symptomatic, stable patients. Moreover, an optimal diagnostic accuracy was also documented in the appraisal of native vessels distal to the graft anastomoses

Double outlet of right ventricle: imaging spectrum on multi-slice computed tomography

Background: Multi-slice computed tomography (MSCT) is the main stay of pre-operative assessment of many complex congenital heart diseases (CHD) in current clinical practice, one of them is double outlet of right ventricle (DORV). DORV is one of the conotruncal anomalies that encompasses a wide spectrum of anatomic malformations in which both the aorta and pulmonary arterial trunk arise entirely or predominantly from the morphologically right ventricle (RV). Purpose of this article is to understand spectrum of DORV and associated types of ventricular septal defect (VSD) on MSCT imaging with special emphasis of usefulness of 3-D volume rendered (VR) images in pre surgical evaluation.Methods: A total of 500 paediatric patients (<18 years old), who had undergone MSCT were studied during the period 2014 to 2019 at the tertiary cardiac care centre.Results: 500 patients having primary/suspicious diagnosis of DORV on echocardiography during the said period were enrolled in the study. All the patients who underwent MSCT scan, were studied in detail for: DORV spectrum, associated types of VSD and its relationship to the semilunar valves. Out of 500 total subjects, subaortic VSD was the most common type of VSD observed (53%), followed by subpulmonic VSD (22%), non-committed VSD (18%) and doubly committed VSD (7%). Associations of pulmonary stenosis, subaortic stenosis and aortic co-arctation with various types of VSDs were addressed. Associated other anomalies were also analysed.Conclusions: Advances in MSCT technology has revolutionized pre-surgical diagnosis, management approach and post-operative follow-up of DORV patients. Excellent image qualities along with 3D volume rendered images help surgeon understand complex morphology of DORV variants and associated types of VSD. Significant reduction in intra and post-operative mortality in DORV patients in current era is result of MSCT technology

Substance P releases and augments the morphine-evoked release of adenosine from spinal cord

The effects of substance P on the morphine-evoked release of adenosine were examined. Substance P alone produced a multiphasic effect on release of adenosine, with release occurring at low nanomolar concentrations and at a micromolar concentration, but not at intermediate concentrations. An inactive dose of substance P augmented the morphine-evoked release of adenosine at a nanomolar concentration of morphine. Release of adenosine by substance P alone (1 nM) or substance P/morphine (100 nM/10 nM) was Ca2(+)-dependent and originated from capsaicin-sensitive nerve terminals

Formulation and Evaluation of Mucoadhesive Buccal Tablet of Repaglinide

The aim of present investigation was formulation and evaluation of mucoadhesive buccal tablet of Repaglinide to study the effect of different polymers on release profile of drug for prolonged release. In this study mucoadhesive buccal tablet were prepared by direct compression method. Various rheological characteristics of the powder bed like bulk density, compressibility index, and angle of repose were evaluated and studied. Mucoadhesive buccal tablets were compressed on a 8 station mini press using 10 mm flat faced punches and were all assessed for weight variation, hardness, thickness, percent swelling index, mucoadhesive strength and in vitro release of the drug by using USP TDT 08L dissolution testing apparatus method II using a paddle at 50 rpm. Data was optimized by using 32 full factorial design by using software named as design expert and with the help of kinetic study. The stability studies showed that there is no decrease in the drug content of all formulations for the period of 2 months. Keywords: Buccal tablet, Repaglinide, HPMC K100M, Xanthan gum

Advances in Developing Therapies to Combat Zika Virus: Current Knowledge and Future Perspectives

Zika virus (ZIKV) remained largely quiescent for nearly six decades after its first appearance in 1947. ZIKV reappeared after 2007, resulting in a declaration of an international “public health emergency” in 2016 by the World Health Organization (WHO). Until this time, ZIKV was considered to induce only mild illness, but it has now been established as the cause of severe clinical manifestations, including fetal anomalies, neurological problems, and autoimmune disorders. Infection during pregnancy can cause congenital brain abnormalities, including microcephaly and neurological degeneration, and in other cases, Guillain-Barré syndrome, making infections with ZIKV a substantial public health concern. Genomic and molecular investigations are underway to investigate ZIKV pathology and its recent enhanced pathogenicity, as well as to design safe and potent vaccines, drugs, and therapeutics. This review describes progress in the design and development of various anti-ZIKV therapeutics, including drugs targeting virus entry into cells and the helicase protein, nucleosides, inhibitors of NS3 protein, small molecules, methyltransferase inhibitors, interferons, repurposed drugs, drugs designed with the aid of computers, neutralizing antibodies, convalescent serum, antibodies that limit antibody-dependent enhancement, and herbal medicines. Additionally, covalent inhibitors of viral protein expression and anti-Toll-like receptor molecules are discussed. To counter ZIKV-associated disease, we need to make rapid progress in developing novel therapies that work effectually to inhibit ZIKV

Repeated Social Defeat Stress Induces an Inflammatory Gut Milieu by Altering the Mucosal Barrier Integrity and Gut Microbiota Homeostasis

Background Posttraumatic stress disorder (PTSD) is a mental health condition triggered by exposure to traumatic events in an individual’s life. Patients with PTSD are also at a higher risk for comorbidities. However, it is not well understood how PTSD affects human health and/or promotes the risk for comorbidities. Nevertheless, patients with PTSD harbor a proinflammatory milieu and dysbiotic gut microbiota. Gut barrier integrity helps to maintain normal gut homeostasis and its dysregulation promotes gut dysbiosis and inflammation. Methods We used a mouse model of repeated social defeat stress (RSDS), a preclinical model of PTSD. Behavioral studies, metagenomics analysis of the microbiome, gut permeability assay (on mouse colon, using an Ussing chamber), immunoblotting, and immunohistochemical analyses were performed. Polarized intestinal epithelial cells and 3-dimensional crypt cultures were used for mechanistic analysis. Results The RSDS mice harbor a heightened proinflammatory gut environment and microbiota dysbiosis. The RSDS mice further showed significant dysregulation of gut barrier functions, including transepithelial electrical resistance, mucin homeostasis, and antimicrobial responses. RSDS mice also showed a specific increase in intestinal expression of claudin-2, a tight junction protein, and epinephrine, a stress-induced neurotransmitter. Treating intestinal epithelial cells or 3-dimensional cultured crypts with norepinephrine or intestinal luminal contents (fecal contents) upregulated claudin-2 expression and inhibited transepithelial electrical resistance. Conclusions Traumatic stress induces dysregulation of gut barrier functions, which may underlie the observed gut microbiota changes and proinflammatory gut milieu, all of which may have an interdependent effect on the health and increased risk of comorbidities in patients with PTSD

Inhibition of Geranylgeranyl Diphosphate Synthase is a Novel Therapeutic Strategy for Pancreatic Ductal Adenocarcinoma

Rab proteins play an essential role in regulating intracellular membrane trafficking processes. Rab activity is dependent upon geranylgeranylation, a post-translational modification that involves the addition of 20-carbon isoprenoid chains via the enzyme geranylgeranyl transferase (GGTase) II. We have focused on the development of inhibitors against geranylgeranyl diphosphate synthase (GGDPS), which generates the isoprenoid donor (GGPP), as anti-Rab agents. Pancreatic ductal adenocarcinoma (PDAC) is characterized by abnormal mucin production and these mucins play important roles in tumor development, metastasis and chemo-resistance. We hypothesized that GGDPS inhibitor (GGDPSi) treatment would induce PDAC cell death by disrupting mucin trafficking, thereby inducing the unfolded protein response pathway (UPR) and apoptosis. To this end, we evaluated the effects of RAM2061, a potent GGDPSi, against PDAC. Our studies revealed that GGDPSi treatment activates the UPR and triggers apoptosis in a variety of human and mouse PDAC cell lines. Furthermore, GGDPSi treatment was found to disrupt the intracellular trafficking of key mucins such as MUC1. These effects could be recapitulated by incubation with a specific GGTase II inhibitor, but not a GGTase I inhibitor, consistent with the effect being dependent on disruption of Rab-mediated activities. In addition, siRNA-mediated knockdown of GGDPS induces upregulation of UPR markers and disrupts MUC1 trafficking in PDAC cells. Experiments in two mouse models of PDAC demonstrated that GGDPSi treatment significantly slows tumor growth. Collectively, these data support further development of GGDPSi therapy as a novel strategy for the treatment of PDAC