Changes in Anti-SARS-CoV-2 IgG Subclasses over Time and in Association with Disease Severity

IgG is the most prominent marker of post-COVID-19 immunity. Not only does this subtype mark the late stages of infection, but it also stays in the body for a timespan of at least 6 months. However, different IgG subclasses have different properties, and their roles in specific anti-COVID-19 responses have yet to be determined. We assessed the concentrations of IgG1, IgG2, IgG3, and IgG4 against different SARS-CoV-2 antigens (N protein, S protein RBD) using a specifically designed method and samples from 348 COVID-19 patients. We noted a statistically significant association between severity of COVID-19 infection and IgG concentrations (both total and subclasses). When assessing anti-N protein and anti-RBD IgG subclasses, we noted the importance of IgG3 as a subclass. Since it is often associated with early antiviral response, we presumed that the IgG3 subclass is the first high-affinity IgG antibody to be produced during COVID-19 infection.     

Investigation of the in vitro and ex vivo acetylcholinesterase and antioxidant activities of traditionally used Lycopodium species from South America on alkaloid extracts

Ethnopharmacological relevance

The study was aimed at evaluating medicinal and therapeutic potentials of two Lycopodiaceae species, Lycopodium clavatum (L.) and Lycopodium thyoides (Humb. & Bonpl. ex Willd), both used in South American folk medicine for central nervous system conditions. Alkaloid extracts were evaluated for chemical characterization, acetylcholinesterase and antioxidant activities.

Materials and methods

The alkaloid extracts obtained by alkaline extraction were determined for each species by GC/MS examination. The evaluation of the anticholinesterase and the antioxidant activities of the extracts were tested by determining in vitro and ex vivo models. Effects on acetylcholinesterase (AChE) were tested in vitro using rat brain homogenates and ex vivo after a single administration (25, 10 and 1 mg/kg i.p.) of the alkaloid extracts in mice. The in vitro antioxidant effects were tested for the 2-deoxyribose degradation, nitric oxide (NO) interaction, 2,2-diphenyl-1-picryl hydrazyl (DPPH) radical scavenging activity and total reactive antioxidant potential (TRAP). After an acute administration (25 and 10 mg/kg i.p.) of the extracts in middle-aged (12 months) mice, the antioxidant effects were estimated through the thiobarbituric acid reactive substances test (TBARS), and the antioxidant enzymes activities for catalase (CAT) and superoxide dismutase (SOD) were measured.

Results

AChE activity was inhibited in vitro by the alkaloid-enriched extracts of both Lycopodium species in a dose and time-dependent manner in rat cortex, striatum and hippocampus. A significant inhibition was also observed in areas of the brain after acute administration of extracts, as well as decreased lipid peroxidation and increased CAT activity in the cortex, hippocampus and cerebellum. A moderate antioxidant activity was observed in vitro for the extracts. Chemically, the main alkaloids found for the two species were lycopodine and acetyldihidrolycopodine.

Conclusion

This study showed that the biological properties of the folk medicinal plants Lycopodium clavatum and Lycopodium thyoides include AChE inhibitory activity and antioxidant effects, two possible mechanisms of action in Alzheimer's related processes.     

Semisynthesis of rosmanol and its derivatives. Easy access to abietatriene diterpenes isolated from the genus Salvia with biological activities

The known diterpenes rosmanol (3), rosmaquinone (4), 7-methoxyrosmanol (5), 7-ethoxyrosmanol (6), galdosol (7), and epirosmanol (8) have been obtained by partial synthesis from carnosol (2), an abundant natural product present in Salvia species. The physical and spectroscopic data of these semisynthetic diterpenes were identical to those of authentic natural samples and with data reported in the literature. These abietane diterpenes have very interesting biological activities and are present in the genus Salviain low quantities; thus, the semisynthetic approach described here represents an efficient alternative method to obtain these compounds. Additionally, the known diterpene 16-hydroxyrosmanol (10) and a new aromatic diterpene 11 were obtained from 16-hydroxycarnosol (9) by reaction with Ph3P/NBS in CH2Cl2. The structure of the new compound 11 was established from its spectroscopic data as 12,16-epoxycarnosol.     

Challenges and rewards of research in marine natural products chemistry in Brazil

Brazil is blessed with a great biodiversity, which constitutes one of the most important sources of biologically active compounds, even if it has been largely underexplored. As is the case of the Amazon and Atlantic rainforests, the Brazilian marine fauna remains practically unexplored in the search for new biologically active natural products. Considering that marine organisms have been shown to be one of the most promising sources of new bioactive compounds for the treatment of different human diseases, the 8000 km of the Brazilian coastline represents a great potential for finding new pharmacologically active secondary metabolites. This review presents the status of marine natural products chemistry in Brazil, including results reported by different research groups with emphasis on the isolation, structure elucidation, and evaluation of biological activities of natural products isolated from sponges, ascidians, octocorals, and Opistobranch mollusks. A brief overview of the first Brazilian program on the isolation of marine bacteria and fungi, directed toward the production of biologically active compounds, is also discussed. The current multidisciplinary collaborative program under development at the Universidade de S?o Paulo proposes to establish a new paradigm toward the management of the Brazilian marine biodiversity, integrating research on the species diversity, ecology, taxonomy, and biogeography of marine invertebrates and microorganisms. This program also includes a broad screening program of Brazilian marine bioresources, to search for active compounds that may be of interest for the development of new drug leads.     

Linfadenitis por micobacterias no tuberculosas: experiencia de 15 años

Objective

To study the epidemiology, clinical features, diagnosis, therapeutic management, and outcome of non-tuberculous mycobacterial lymphadenitis in a paediatric population of Aragón (Spain).

Visual symptoms as the first manifestation of Alzheimer's disease

CASE REPORT: We report a 59-year-old patient with difficulty in visual perception, difficulty reading and episodes of dyschromatopsia. The ocular examination was unremarkable. Structural neuro-imaging and neuro-ophthalmology tests were normal. Positron emission tomography scanning showed decreased metabolism in the parieto-occipital cortex bilaterally. Several months later the patient developed Alzheimer's disease. DISCUSSION: Visual symptoms may be the first manifestation of Alzheimer's disease.     

Early pregnancy losses in in vitro fertilization and oocyte donation

Objective: To evaluate prospectively the incidence of early pregnancy losses (before menstruation occurs) in IVF and ovum donation cycles.

Design: Prospective case-control study.

Setting: Tertiary care, university-associated center.

Patient(s): One hundred forty-five patients undergoing IVF and 92 undergoing oocyte donation were recruited. The control group for IVF consisted of 15 ovum donors who had no ET and were instructed to avoid intercourse. The control group for oocyte donation included 10 women undergoing a mock cycle of steroid replacement.

Intervention(s): Starting on day 6 after ET, the women were instructed to collect the first urine sample of the day every 2 days. Each patient collected six different specimens of urine (days 6, 8, 10, 12, 14, and 16 after ET for cases or the same days without ET for controls.

Main Outcome Measure(s): β-HCG was measured with a standardized microparticle enzyme immunoassay, and IVF reproductive outcome was assessed.

Result(s): For IVF, positive implantation was registered in 88 of 145 cycles of embryo replacement (60.7%). Only 30 (20.7%) resulted in viable pregnancies, whereas the remaining 58 miscarried. Forty-two of these miscarriages (72.4%) were early pregnancy losses and 13 (22.4%) were classified as clinical abortions. In ovum donation, positive implantation was recorded in 64 of 92 cycles of ET (69.6%). A total of 30 (32.6%) ended in viable pregnancies, whereas the remaining 34 (37.0%) were miscarriages. Early pregnancy loss accounted for 70.6% of pregnancy losses, whereas biochemical pregnancies and clinical abortions accounted for 11.8% and 17.6%, respectively.

Conclusion(s): Our results demonstrate that patients undergoing assisted reproductive technology have an increased rate of early pregnancy loss compared with fertile patients. In addition, these data indicate that implantation is more frequently impaired in IVF than in oocyte donation cycles, resulting in a high incidence of early pregnancy loss. This suggests that implantation may be subjected to abnormal conditions in assisted reproduction.