Wunderlich syndrome as a rare complication of polyarteritis nodosa: a case report.

Spontaneous subcapsular and perirenal hemorrhage, known as Wunderlich syndrome (WS), is a rare clinical manifestation of polyarteritis nodosa (PAN). We report a case of a 48-year-old male with a history of recurrent episodes of leg muscle tenderness and dysesthesia, bilateral flank pain, painful nodular skin lesions in the lower limbs, weight loss, and difficult-to-control arterial hypertension. The abdominopelvic computed tomography angiography showed a large left perirenal hematoma, leading to the patient's admission to the intensive care unit. After the exclusion of infectious or neoplastic foci, the patient was diagnosed with PAN and started intravenous methylprednisolone pulses with a good response. Since WS is a rare initial clinical manifestation of PAN, an early diagnosis and aggressive treatment will significantly improve clinical outcomes.

Developments in the chemistry and biology of 1,2,3-triazolyl-C-nucleosides.

In the last 50 years, nucleoside analogs have been introduced to drug therapy as antivirals for different types of cancer due to their interference in cellular proliferation. Among the first line of nucleoside treatment drugs, ribavirin (RBV) is a synthetic N-nucleoside with a 1,2,4-triazole moiety that acts as a broad-spectrum antiviral. It is on the World Health Organization (WHO) list of essential medicines. However, this important drug therapy causes several side effects due to its nonspecific mechanism of action. There is thus a need for a continuous study of its scaffold. A particular approach consists of connecting  d-ribose to the nitrogen-containing base with a C-C bond. It provides more stability against enzymatic action and a better pharmacologic profile. The coronavirus disease (COVID) pandemic has increased the need for more solutions for the treatment of viral infections. Among these solutions, remdesivir, the first C-nucleoside, has been approved by the Food and Drug Administration (FDA) for clinical use against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It drew attention to the study of the C-nucleoside scaffold. Different C-nucleoside patterns have been synthesized over the years. They show many important activities against viruses and cancer cell lines. 1,2,3-Triazolyl-C-nucleoside derivatives are a prolific and efficient subclass of RBV analogs close to the already-known RBV with a C-C bond modification. These compounds are often prepared by alkynylation of the  d-ribose ring followed by azide-alkyne cycloaddition. They are reported to be active against the Crimean-Congo hemorrhagic fever virus and several tumoral cell lines, showing promising biological potential. In this review, we explore such approaches to 1,2,3-triazolyl-C-nucleosides and their evolution over the years.

Adherence to COVID-19 health protocols in an online news context in the Philippines: A manifest content analysis.

OBJECTIVES: Globally, adherence to COVID-19 health and safety protocols played a crucial role in preventing the spread of the virus. Thus, this study analyzed online news articles reporting adherence to COVID-19 health and safety protocols in the Philippines. DESIGN: Manifest content analysis. SAMPLE: News articles (n = 192) from three major online news portals in the Philippines. MEASUREMENT: Published online news articles were collected during the peak of the COVID-19 pandemic (March 2020 to March 2021). Bengtsson's content analysis approach was used to analyze the data. Member-checking and intercoder reliability validated the study's results. RESULTS: Three main themes emerged: (a) adherence, (b) non-adherence, and (c) partial adherence. The subthemes were labeled who, what, when, where, and why. The same behavior, social distancing, was the most adhered to and non-adhered COVID-19 health protocol. This protocol has the highest occurrences in political protest, religious-related activities, and self-initiated quarantine. Leisure activities both showed non-adherence and partial adherence. CONCLUSIONS: Online news articles depicted Filipinos' adherence to health and safety protocols. Their adherence was primarily determined by one's group or community, social norms, and values. The government and its public health agencies should strengthen current efforts and continuously re-evaluate existing policies to modify ineffective and confusing safety health protocols.

The synergy between nucleotide biosynthesis inhibitors and antiviral nucleosides: New opportunities against viral infections?

5'-Phosphorylated nucleoside derivatives are molecules that can be found in all living organisms and viruses. Over the last century, the development of structural analogs that could disrupt the transcription and translation of genetic information culminated in the development of clinically relevant anticancer and antiviral drugs. However, clinically effective broad-spectrum antiviral compounds or treatments are lacking. This viewpoint proposes that molecules that inhibit nucleotide biosynthesis may sensitize virus-infected cells toward direct-acting antiviral nucleosides. Such potentially synergistic combinations might allow the repurposing of drugs, leading to the development of new combination therapies.

Studies on the synthesis of 1'-CN-triazolyl-C-ribosides.

The search for broad-spectrum antiviral compounds is a continuous mandatory effort. The recent approval of the first C-nucleoside carrying a nitrile as a substituent at the C1' position of the ribose ring has raised interest in this underexplored substitution pattern. We have previously reported the development of different 1,2,3-triazolyl-C-ribonucleosides with anticancer and antiviral activities. Herein we report our results on the incorporation of a C1'-CN group in 1,2,3-triazolyl-C-ribonucleosides.

Strategies Towards the Synthesis of N2-Substituted 1,2,3-Triazoles.

The chemistry of 1,2,3-triazoles gained much attention since the discovery of the copper catalyzed Alkyne-azide cycloaddition (CuAAC) reaction which delivers exclusively the 1,4-regioisomer in high yields. On the other hand there is still no universal methodology capable of delivering the N2 substituted regioisomer. The unique properties of these N2-substituted 1,2,3-triazoles have stimulated synthetic efforts on the developments of methodologies capable of delivering it in high yield and selectivity. These efforts are the subject of the presented review.

Antimycobacterial and anti-inflammatory activities of substituted chalcones focusing on an anti-tuberculosis dual treatment approach.

Tuberculosis (TB) remains a serious public health problem aggravated by the emergence of M. tuberculosis (Mtb) strains resistant to multiple drugs (MDR). Delay in TB treatment, common in the MDR-TB cases, can lead to deleterious life-threatening inflammation in susceptible hyper-reactive individuals, encouraging the discovery of new anti-Mtb drugs and the use of adjunctive therapy based on anti-inflammatory interventions. In this study, a series of forty synthetic chalcones was evaluated in vitro for their anti-inflammatory and antimycobacterial properties and in silico for pharmacokinetic parameters. Seven compounds strongly inhibited NO and PGE2 production by LPS-stimulated macrophages through the specific inhibition of iNOS and COX-2 expression, respectively, with compounds 4 and 5 standing out in this respect. Four of the seven most active compounds were able to inhibit production of TNF-α and IL-1ß. Chalcones that were not toxic to cultured macrophages were tested for antimycobacterial activity. Eight compounds were able to inhibit growth of the M. bovis BCG and Mtb H37Rv strains in bacterial cultures and in infected macrophages. Four of them, including compounds 4 and 5, were active against a hypervirulent clinical Mtb isolate as well. In silico analysis of ADMET properties showed that the evaluated chalcones displayed satisfactory pharmacokinetic parameters. In conclusion, the obtained data demonstrate that at least two of the studied chalcones, compounds 4 and 5, are promising antimycobacterial and anti-inflammatory agents, especially focusing on an anti-tuberculosis dual treatment approach.

Vitamin D - immunomodulatory actions and new potentialities.

The authors intend to make a brief scientific review about the immunoregulatory potentialities underlying vitamin D providing an insight in areas such as multiple sclerosis, disorders of cognitive function, response to infection and neoplasia.

Nasal type extranodal NK/T cell lymphoma diagnosed in a patient with rheumatoid arthritis under methotrexate.

Rheumatoid arthritis (RA) patients have increased risk of lymphoma which seems associated mainly with high inflammatory state and disease activity, but also with immunosuppressive agents or Epstein-Barr virus (EBV) infection. Many case reports describe lymphoproliferative lesions arising during methotrexate therapy, often EBV positive with possible regression after methotrexate withdrawal. The authors report the case of an 85-year-old patient with erosive and seronegative RA, in remission under methotrexate who developed a midfacial destructive lesion with epistaxis and local inflammatory signs. The magnetic resonance imaging showed a large nasal septum defect. Anti-neutrophil cytoplasmic antibodies titres and angiotensin converting enzyme were normal. Biopsies of the lesion identified a NK/ T nasal type lymphoma. EBV latent membrane protein research on the lesion was negative. Polymerase chain reaction analysis of the bone marrow aspirate showed EBV DNA positivity. Withdrawal of methotrexate was performed without tumour regression. The authors described the single case of a patient with RA in stable remission under methotrexate who presented a rare type of lymphoma, a nasal type NK/T. EBV active replication was found in the bone marrow.

Conformational dissection of Thermomyces lanuginosus lipase in solution.

Lipases are triacyl glycerol acyl hydrolases, which catalyze hydrolysis of esters, esterification and transesterification reactions, among others. Some of these enzymes have a large hydrophobic pocket covered by an alpha-helical mobile surface loop (the lid). Protein-protein interactions can occur through adsorption of two open lids of individual lipases. We investigated the conformation and oligomeric state of Thermomyces lanuginosus lipase (TLL) in solution by spectroscopic and mass spectrometry techniques. Information about oligomerization of this important industrial enzyme is only available for TLL crystals; therefore, we have done a throughout investigation of the conformation of this lipase in solution. SDS-PAGE and mass spectrometry analysis of size-exclusion chromatography eluted fractions indicated the presence of both monomeric and dimeric populations of TLL. The stability of the enzyme upon thermal and guanidine hydrochloride treatment was examined by circular dichroism and fluorescence emission spectroscopy. Small angle x-ray scattering and ion mobility mass spectrometry analysis revealed that TLL is found as a mixture of monomers and dimers at the assayed concentrations. Although previous x-ray diffraction data showed TLL as a dimer in the crystal (PDB: 1DT3), to our knowledge our report is the first evidencing that TLL co-exists as stable dimeric and monomeric forms in solution.

A comprehensive study on the activity and deactivation of immobilized Lecitase Ultra in esterifications of food waste streams to monoacylglycerols.

Lecitase Ultra was immobilized on Amberlites XAD2 and XAD4, through physical entrapping under conventional stirring or ultrasound irradiation, and characterized by standard techniques. The resulting immobilized biocatalysts were utilized in the valorization of an acidic food-derived residue from a palm oil refining process to produce monoacylglycerols from isopropylidene glycerol under batch and continuous flow conditions. Results indicated that the immobilized biocatalysts could moderately convert the food waste residue (max. conversion 50-60 %), exhibiting interesting stability under continuous flow conditions.

Severe gram positive bacterial infection in an ulcerative colitis patient treated with Infliximab.

Tumour necrosis factor-alpha (TNF-α) inhibitors represent an important treatment advance for a number of inflammatory conditions, including inflammatory bowel disease. Since their introduction in 1999, it has become clear that some biological therapies may be associated with an increased risk for bacterial infections. Herein we present the first case of septic arthritis and spine empyema, caused by S. aureus, in a 63 year-old patient with ulcerative colitis, who was under treatment with Infliximab and with 40mg per day of prednisolone.