Coralyne is an important alkaloid due to its anti-cancer and other medicinal properties. It targets DNA in cells and acts as human topoisomerase-I poison, telomerase inhibitor and nucleic acid intercalator. It has high tendency to undergo self-association, which is a matter of concern for therapeutic applications. The understanding of its interaction with DNA requires precise knowledge of chemical shifts in Nuclear Magnetic Resonance (NMR) spectra besides self-association. The present study is the first report of a complete assignment of all 1H/13C resonances in NMR spectra of coralyne in DMSO-d6 using one dimensional 1H/13C and two dimensional NMR experiments. The chemical shift of all proton and several 13C resonances have also been obtained in D2O and ethanol-d6. The same has been calculated using Density Functional Theory (DFT). NMR spectra of coralyne show upfield shift of 0.6-1.2 ppm in aromatic ring protons suggesting stacking interactions. Apart from 11 intra molecular NOE cross peaks in 2D 1H-1H ROESY spectra, 3 short distance NOE correlations, H6-10OCH3, H5-10OCH3 and H12-16CH3, give direct independent evidence of the formation of a stacked dimer. The absorbance, fluorescence, circular dichroism and fluorescence lifetime experiments conducted in the present investigations corroborate results obtained by NMR.

Adenoviral keratoconjunctivitis is caused by adenovirus serotypes 8,19,37.Typical signs of adenoviral con-junctivitis include preauricular lymphadenopathy, conjunc-tival hyperemia, chemosis, subconjunctival hemorrhage and follicular conjunctival reaction. Corneal involvement in adenoviral keratoconjunctivitis is variable. Most patients have a diffuse, fine, superficial keratitis with focal, elevated, punctate epithelial lesions which become subepithelial opacities later. We had a 35 years old male who had unusual clinical presentation of adenoviral conjunctivitis in the form of conjunctivo-corneal epithelitis which has not been described in the literature.Patient was managed successfully by conserva-tive treatment alone. Conjunctivo-corneal epithelitis can be unusual clinical presentation of adenoviral kerato-conjunctivitis.

Background/Aims: Exclusive enteral nutrition (EEN) is recommended for induction of remission in pediatric Crohn’s disease (CD). However, it is not currently recommended for inducing remission in adults. This report describes the use of 12-week EEN for induction of remission in anti-tumor necrosis factor (anti-TNF) refractory adult CD. Methods: This is a retrospective analysis of adults with moderate to severe active (Crohn’s Disease Activity Index [CDAI] >220) anti-TNF refractory CD, who received EEN for 12 weeks between April 2018 and March 2019 at Dayanand Medical College and Hospital, Ludhiana, India. Primary outcomes included achievement of clinical remission and fistula healing at 12 weeks. Improvement in inflammatory markers and nutritional status were the secondary end points. Results: Out of 23 patients who received anti-TNF agents, 7 (30.4%) were refractory and were offered EEN as a salvage therapy. Six patients (66.7% females, mean age 25.6±6.5 years) consented. Four patients (66.6%) achieved clinical remission (CDAI <150). Mean CDAI of patients decreased significantly after 12 weeks of EEN (388.8±74.8 vs. 160.0±25.2, P<0.001). Perianal fistulas showed clinical response (drainage decreased by >50%), though none achieved remission. Entero-enteric fistulae showed complete healing. Mean body mass index improved from 15.6±3.1 to 18.9±1.9 kg/m2 at week 12 (P=0.003). Hemoglobin and serum albumin also improved from 8.2±1.1 g/dL and 2.8±0.3 g/dL at baseline to 12.6±0.6 g/dL and 3.6±0.5 g/dL post-EEN respectively (P<0.001 and P=0.006 respectively). Conclusions EEN appears to be an effective and well tolerated therapy for induction of remission in anti-TNF refractory adult CD. More data from prospective trials with larger number of patients is required.

Neurolymphomatosis (NL) defined as infiltration of the central nervous system or the peripheral nervous system (PNS) by malignant lymphoma cells is a rare clinical entity. However, the increasing use of fluorodeoxyglucose positron-emission tomography (FDG-PET) and magnetic resonance imaging in evaluating PNS disorders is resulting in; this condition being recognized more frequently. Here; we report five NL patients and review the current literature. We report five patients with non-Hodgkin's lymphoma (NHL) and NL, all of whom were men aged 47-69 years. The clinical presentation varied from symmetrical peripheral neuropathy to mononeuropathy. Peripheral neuropathy was the presenting manifestation of a systemic lymphoma in two patients (40%). Neuroimaging as well as whole-body FDG-PET helped in determining the correct diagnosis in all of the patients. NL is an unusual presentation of NHL resulting from infiltration of the PNS by malignant lymphomatous cells. While evaluating peripheral neuropathy, a high degree of suspicion of NL is required since the presenting symptoms vary, conventional radiology has only modest sensitivity, and a pathological diagnosis is often difficult. FDG-PET helps in the early diagnosis and treatment of this condition.
Animals ; Central Nervous System ; Diagnosis ; Early Diagnosis ; Humans ; Lymphoma ; Lymphoma, Non-Hodgkin ; Magnetic Resonance Imaging ; Male ; Marek Disease* ; Mononeuropathies ; Neuroimaging ; Peripheral Nervous System ; Peripheral Nervous System Diseases ; Positron-Emission Tomography

Neurolymphomatosis (NL) defined as infiltration of the central nervous system or the peripheral nervous system (PNS) by malignant lymphoma cells is a rare clinical entity. However, the increasing use of fluorodeoxyglucose positron-emission tomography (FDG-PET) and magnetic resonance imaging in evaluating PNS disorders is resulting in; this condition being recognized more frequently. Here; we report five NL patients and review the current literature. We report five patients with non-Hodgkin's lymphoma (NHL) and NL, all of whom were men aged 47-69 years. The clinical presentation varied from symmetrical peripheral neuropathy to mononeuropathy. Peripheral neuropathy was the presenting manifestation of a systemic lymphoma in two patients (40%). Neuroimaging as well as whole-body FDG-PET helped in determining the correct diagnosis in all of the patients. NL is an unusual presentation of NHL resulting from infiltration of the PNS by malignant lymphomatous cells. While evaluating peripheral neuropathy, a high degree of suspicion of NL is required since the presenting symptoms vary, conventional radiology has only modest sensitivity, and a pathological diagnosis is often difficult. FDG-PET helps in the early diagnosis and treatment of this condition.
Animals ; Central Nervous System ; Diagnosis ; Early Diagnosis ; Humans ; Lymphoma ; Lymphoma, Non-Hodgkin ; Magnetic Resonance Imaging ; Male ; Marek Disease* ; Mononeuropathies ; Neuroimaging ; Peripheral Nervous System ; Peripheral Nervous System Diseases ; Positron-Emission Tomography

Objective: To evaluate the epidemiology of candidiasis and the antifungal susceptibility profile of Candida species isolated from the intensive care unit (ICU) patients. Methods: The study used a qualitative descriptive design. Relevant samples depending on organ system involvement from 100 ICU patients were collected and processed. Identification and speciation of the isolates was conducted by the biochemical tests. Antifungal susceptibility testing was carried out as per CLSI-M27-A3 document. Results: Ninety Candida isolates were isolated from the different clinical samples: urine (43.3%), tracheal aspirate (31.1%), urinary catheter (12.2%), endotracheal tube (7.8%), abdominal drains (3.3%), sputum (2.2%). The incidence of candidiasis caused by non-albicans Candida (NAC) species (63.3%) was higher than Candida albicans (36.7%). The various NAC species were isolated as: Candida tropicalis (41.1%), Candida glabrata (10%), Candida parapsilosis (6.7%), Candida krusei (3.3%) and Candida kefyr (2.2%). The overall isolation rate of Candida species from samples was 53.3%. Antifungal susceptibility indicated that 37.8% and 7.8% of the Candida isolates were resistant to fluconazole and amphotericin B, respectively. Conclusions: Predominance of NAC species in ICU patients along with the increasing resistance being recorded to fluconazole which has a major bearing on the morbidity and management of these patients and needs to be further worked upon.

While Mek1/2 and Gsk3β inhibition ("2i") supports the maintenance of murine embryonic stem cells (ESCs) in a homogenous naïve state, prolonged culture in 2i results in aneuploidy and DNA hypomethylation that impairs developmental potential. Additionally, 2i fails to support derivation and culture of fully potent female ESCs. Here we find that mouse ESCs cultured in 2i/LIF supplemented with lipid-rich albumin (AlbuMAX) undergo pluripotency transition yet maintain genomic stability and full potency over long-term culture. Mechanistically, lipids in AlbuMAX impact intracellular metabolism including nucleotide biosynthesis, lipid biogenesis, and TCA cycle intermediates, with enhanced expression of DNMT3s that prevent DNA hypomethylation. Lipids induce a formative-like pluripotent state through direct stimulation of Erk2 phosphorylation, which also alleviates X chromosome loss in female ESCs. Importantly, both male and female "all-ESC" mice can be generated from de novo derived ESCs using AlbuMAX-based media. Our findings underscore the importance of lipids to pluripotency and link nutrient cues to genome integrity in early development.
Male ; Animals ; Female ; Mice ; Mouse Embryonic Stem Cells ; Embryonic Stem Cells ; Genomic Instability ; Lipids ; DNA/metabolism* ; Cell Differentiation