Halogenated Rocaglate Derivatives: Pan-antiviral Agents against Hepatitis E Virus and Emerging Viruses.

The synthesis of a library of halogenated rocaglate derivatives belonging to the flavagline class of natural products, of which silvestrol is the most prominent example, is reported. Their antiviral activity and cytotoxicity profile against a wide range of pathogenic viruses, including hepatitis E, Chikungunya, Rift Valley Fever virus and SARS-CoV-2, were determined. The incorporation of halogen substituents at positions 4', 6 and 8 was shown to have a significant effect on the antiviral activity of rocaglates, some of which even showed enhanced activity compared to CR-31-B and silvestrol.

Treatment of a Heavily Calcified Celiac Artery Ostial Subtotal Occlusion Using Shockwave Lithotripsy: A Novel Approach.

PURPOSE: We present the novel use of adjunctive intravascular lithotripsy (IVL) before definitive intravascular stenting of a heavily calcified celiac artery ostial occlusion. CASE REPORT: A 79-year-old woman presented with chronic post-prandial abdominal pain and weight loss. Selective angiography revealed a sub-totally occluded celiac artery. Percutaneous endovascular intervention of the celiac artery was attempted but was unsuccessful because of heavy calcification. The patient returned for a repeat procedure. A guidewire was successfully advanced across the sub-totally occluded ostium. A Shockwave Lithotripsy BDC 7.0-mm/60-mm balloon catheter (Shockwave Medical Inc., Santa Clara, California) was successfully used to modify the calcified plaque. Next, a stent was deployed for definitive therapy. The final angiogram showed an excellent result. The patient tolerated the procedure well and was sent home on dual antiplatelet therapy. Nine months after the procedure, she had gained weight and denied any further post-prandial abdominal pain. CONCLUSION: IVL treatment modality to modify calcified lesions in the splanchnic circulation should be considered as a novel approach to patients in whom traditional endovascular treatment modalities are thought to be suboptimal. Further controlled studies are needed to access the safety, feasibility, and efficacy of the use of this novel technology in this vascular territory.

Rocaglamide and silvestrol: a long story from anti-tumor to anti-coronavirus compounds.

Covering: up to the beginning of 2020Many natural substances have been transformed again and again with regard to their pharmaceutical-medical potential, including new members of a growing class of natural products, the flavaglines. Important representatives are rocaglamide and silvestrol, isolated from the Aglaia species, which are highlighted here. These products started as potential anti-tumor agents five decades ago and have recently proved to be very promising antiviral agents, especially against RNA viruses. Today they are discussed as potential starting compounds for developing drug candidates and therapeutics.

Characterization of the promiscuous N-acyl CoA transferase, LgoC, in legonoxamine biosynthesis.

More than 500 siderophores are known to date, but only three were identified to be aryl-containing hydroxamate siderophores, legonoxamines A and B from Streptomyces sp. MA37, and aryl ferrioxamine 2 from Micrococcus luteus KLE1011. Siderophores are produced by microorganisms to scavenge iron from the environment, thereby making this essential metal nutrient available to the microbe. We demonstrate here that LgoC from MA37 is responsible for the key aryl-hydroxamate forming step in legonoxamine biosynthesis. Biochemical characterization established that LgoC displays considerable promiscuity for the acylation between N-hydroxy-cadaverine and SNAC (N-acetylcysteamines) thioester derivatives.

Autoimmune-Associated Hemophagocytosis and Myelofibrosis in a Newly Diagnosed Lupus Patient: Case Report and Literature Review.

Bone marrow abnormalities in SLE are now becoming increasingly recognized, suggesting that the bone marrow may also be an important site of target organ damage. In this study, we present a rare case of concurrent autoimmune hemophagocytic syndrome and autoimmune myelofibrosis, potentially life-threatening conditions, in a newly diagnosed SLE patient. We report a case of a 30-year-old Filipino woman who presented with a one-year history of fever, constitutional symptoms, exertional dyspnea, joint pains, and alopecia and physical examination findings of fever, facial flushing, cervical lymphadenopathies, and knee joint effusions. Laboratory workup revealed pancytopenia with leukoerythroblastosis, elevated ESR, increased serum levels of transaminases, elevated CRP and LDH, hyperferritinemia, hypertriglyceridemia, proteinuria, hepatomegaly, and positive antinuclear antibody. Bone marrow aspiration and trephine biopsy revealed hemophagocytosis and moderate myelofibrosis. The patient was diagnosed with SLE with concomitant autoimmune-associated hemophagocytic syndrome and autoimmune myelofibrosis. Treatment with high-dose corticosteroids led to dramatic clinical improvement with normalization of laboratory data and complete resolution of bone marrow hemophagocytosis and myelofibrosis. Hemophagocytosis and myelofibrosis, although uncommon, are possible initial manifestations of SLE and should be included in the differential diagnosis of cytopenias in SLE. Thorough clinical assessment and microscopic bone marrow examination and timely initiation of corticosteroid therapy are essential in the diagnosis and management of these potentially life-threatening conditions. This case emphasizes that the bone marrow is an important site of target organ damage in SLE, and evaluation of cytopenias in SLE should take this into consideration.

Signet-ring cell adenocarcinoma of unknown primary presenting with superior vena cava (SVC) syndrome: rare type of cancer.

A 53-year-old man presented with a 3-month history of progressive, non-productive cough followed by occasional swelling of the face and upper extremities. Physical examination on admission revealed prominent superficial vessels at the neck and upper extremity swelling. Bronchoscopy revealed the superior segment of the right lower lobe was narrow but without visible mass; cell block and biopsy done revealed signet-ring cell carcinoma with an immunohistochemistry pattern favouring the primary site of malignancy as either gastric or of the pancreaticobiliary tree. However, CT scan of the abdomen and pelvis with triple contrast revealed only slight gastric wall thickening; the pancreas was unremarkable. The patient underwent radiotherapy with noted improvement of symptoms. He was then discharged with plans for further work-up on an outpatient basis. This work highlights the importance of a comprehensive histopathological and immunohistochemical work-up which can help predict a site of origin to be able to provide the appropriate management.

Electron paramagnetic resonance spectroscopy studies of oxidative degradation of an active pharmaceutical ingredient and quantitative analysis of the organic radical intermediates using partial least-squares regression.

Electron paramagnetic resonance (EPR) spectroscopy was used to study the radical species formed during the oxidation of an active pharmaceutical ingredient in the solid state. It was found that the extent of radical generation correlated to the formation of an oxidative degradation product. Multifrequency EPR and electron nuclear double resonance spectroscopy gave additional information on the identity of the organic radical species involved in the oxidation process, and a mechanism was proposed for the degradation, involving the formation of both carbon-centered and peroxy radicals. The multivariate analysis technique of partial least-squares (PLS) regression was then used to determine the extent of oxidation of the active pharmaceutical ingredient from the EPR spectra. The suitability of this approach was demonstrated from its application to a series of standards. The conventional approach for the quantitative analysis of EPR spectra is to measure the peak height or to perform double integration of the spectral region containing the signal of interest. Both of these methods have intrinsic errors associated with them, particularly for weak EPR signals with a poor signal-to-noise ratio or a sloping background response. The results obtained showed that greatly improved quantitation was obtained using the PLS regression approach.