Heart Rate Reduction Prevents The Global Phenotype Of Post-myocardial LV Infarction Remodeling

Rationale LV remodeling is a crucial phenomenon of adaptation/maladaptation to heart diseases and plays a major role in HF progression after myocardial infarction. We tested if in a post-MI rat model, a pure HR reduction by ivabradine (IVA) is able to modulate structural and electrophysiological remodeling processes. Methods IVA (10 mg/kg/d) was given in drinking water for 3 months to Wistar rats, 7 days after LAD ligation (MI). SHAM rats (n = 14) were used as control (untreated; n = 14) or for electrophysiology (IVA; n = 7). MI rats were randomly allocated to IVA (n = 17) or vehicle (n = 15). At 3 months, end-diastolic volume (EDV), end-systolic volume (ESV) and EF were evaluated by echocardiography. BNP was tested in plasma by IEA. IVA effect on transient K+ outward current (Ito), the main current changed in HF, was recorded in single LV myocyte (LVM) in whole-cell configuration by applying a voltage protocol activation. OH-proline, an indirect index of collagen content in LV, was measured by spectrophotometry (n = 6/group). Results Echocardiography: At 3 months, in MI, IVA significantly reduced HR (208 ± 5 bpm vs. 235 ± 4, p < 0.05). ESV increased in MI vs. control SHAM (0.78 ± 0.10 vs. 0.41 ± 0.03 ml) while it was significantly reduced by IVA (0.54 ± 0.1 ml, p < 0.05). As there is no effect on EDV, IVA improved EF (62.8 ± 1.7 vs. 54.7 ± 2.3%, p < 0.05) in MI. Neuroendocrine response. Circulating BNP significantly increased in MI vs. control SHAM (2.2 ± 0.2 vs. 1.4 ± 0.1 ng/ml, p < 0.01) and tended to be reduced in MI treated rats. Electrophysiology: IVA did not change peak Ito density measured at +50 mV in LVMs from SHAM. Significantly reduced in LVMs from MI untreated rats (5.1 ± 0.7 pA/pF, n = 30, p < 0.01) vs. SHAM, peak Ito was partially restored in LVMs from MI treated rats (7.3 ± 0.8 pA/pF, n = 28, p < 0.05). Interstitial remodeling: IVA significantly reduced OH-proline content in MI vs. control SHAM (9.03 ± 1.93 vs. 14.85 ± 1.70 µg/mg dry weight, p < 0.05), which is significantly correlated with infarct scare (r = 0.887, p = 0.0001) and HR (r = 0.593, p < 0.05). Conclusions HR reduction by IVA prevents electrophysiological as well as mechanical, cellular and interstitial alteration during post-MI LV remodeling. These results reinforce the potential interest of HR reduction in HF management

Chemical composition and biological activities of Guatteria elliptica R. E. Fries (Annonaceae) essential oils

Leaf from two Guatteria elliptica R. E. Fries (Annonaceae) specimens were collected at Paranapiacaba and Caraguatatuba in Sao Paulo (Brazil). The essential oils presented (GC/GC-MS), as major compound, spathulenol (53.9%) for the Paranapiacaba specimen and caryophyllene oxide (40.9%) for Caraguatatuba. The oils showed low antioxidant activity with EC50 = 7.24 +/- 1.03 and 28.68 +/- 5.78 mg/mL, respectively, for Paranapiacaba and Caraguatatuba specimens. Both oils did not show a relevant (MIC > 3 mg/mL) antimicrobial activity. However, the Paranapiacaba oil presented an important antitumour activity against breast and prostate cancer cells (IC50 = 7.01 +/- 0.23 and 5.35 +/- 0.35 mu g/mL, respectively) and a low cytotoxicity against normal fibroblast cells (IC50 > 22.27 e IC10 = 18.55 +/- 1.89 mu g/mL). Isolated major compound, spathulenol, showed good activity against MCF-7 and PC-3 with IC50 = 5.38 +/- 0.20 and 2.25 +/- 0.28 mu g/mL mu g/mL, respectively.CAPESCNPqFAPESPUniv Sao Paulo, Fac Pharmaceut Sci, Sao Paulo, BrazilSao Paulo Bot Inst, Nucleus Res Physiol & Biochem, Sao Paulo, BrazilUniv Paulista, Lab Extract, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Exact Sci & Earth, Diadema, BrazilUniv Sao Paulo, Inst Chem, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Exact Sci & Earth, Diadema, BrazilWeb of Scienc

Inhibition of the α-carbonic anhydrase from Vibrio cholerae with amides and sulfonamides incorporating imidazole moieties

We discovered novel and selective sulfonamides/amides acting as inhibitors of the a-carbonic anhydrase (CA, EC 4.2.1.1) from the pathogenic bacterium Vibrio cholerae (VchCA). This Gram-negative bacterium is the causative agent of cholera and colonises the upper small intestine where sodium bicarbonate is present at a high concentration. The secondary sulfonamides and amides investigated here were potent, low nanomolar VchCA inhibitors whereas their inhibition of the human cytosolic isoforms CA I and II was in the micromolar range or higher. The molecules represent an interesting lead for antibacterial agents with a possibly new mechanism of action, although their CA inhibition mechanism is unknown for the moment

Nine-Year Nationwide Environmental Surveillance of Hepatitis E Virus in Urban Wastewaters in Italy (2011–2019)

Hepatitis E virus (HEV) is an emerging causative agent of acute hepatitis worldwide. To provide insights into the epidemiology of HEV in Italy, a large-scale investigation was conducted into urban sewage over nine years (2011&ndash;2019), collecting 1374 sewage samples from 48 wastewater treatment plants located in all the 20 regions of Italy. Broadly reactive primers targeting the ORF1 and ORF2 regions were used for the detection and typing of HEV, followed by Sanger and next generation sequencing (NGS). Real-time RT-qPCR was also used to attempt quantification of positive samples. HEV RNA detection occurred in 74 urban sewage samples (5.4%), with a statistically significant higher frequency (7.1%) in central Italy. Fifty-six samples were characterized as G3 strains and 18 as G1. While the detection of G3 strains occurred in all the surveillance period, G1 strains were mainly detected in 2011&ndash;2012, and never in 2017&ndash;2019. Typing was achieved in 2 samples (3f subtype). Viral concentrations in quantifiable samples ranged from 1.2 &times; 103 g.c./L to 2.8 &times; 104 g.c./L. Our results suggest the considerable circulation of the virus in the Italian population, despite a relatively small number of notified cases, a higher occurrence in central Italy, and a noteworthy predominance of G3 strains

Characterization of SARS-CoV-2 Variants in Military and Civilian Personnel of an Air Force Airport during Three Pandemic Waves in Italy

We investigated SARS-CoV-2 variants circulating, from November 2020 to March 2022, among military and civilian personnel at an Air Force airport in Italy in order to classify viral isolates in a potential hotspot for virus spread. Positive samples were subjected to Next-Generation Sequencing (NGS) of the whole viral genome and Sanger sequencing of the spike coding region. Phylogenetic analysis classified viral isolates and traced their evolutionary relationships. Clusters were identified using 70% cut-off. Sequencing methods yielded comparable results in terms of variant classification. In 2020 and 2021, we identified several variants, including B.1.258 (4/67), B.1.177 (9/67), Alpha (B.1.1.7, 9/67), Gamma (P.1.1, 4/67), and Delta (4/67). In 2022, only Omicron and its sub-lineage variants were observed (37/67). SARS-CoV-2 isolates were screened to detect naturally occurring resistance in genomic regions, the target of new therapies, comparing them to the Wuhan Hu-1 reference strain. Interestingly, 2/30 non-Omicron isolates carried the G15S 3CLpro substitution responsible for reduced susceptibility to protease inhibitors. On the other hand, Omicron isolates carried unusual substitutions A1803V, D1809N, and A949T on PLpro, and the D216N on 3CLpro. Finally, the P323L substitution on RdRp coding regions was not associated with the mutational pattern related to polymerase inhibitor resistance. This study highlights the importance of continuous genomic surveillance to monitor SARS-CoV-2 evolution in the general population, as well as in restricted communities

Hepatitis A Virus Strains Circulating in the Campania Region (2015–2018) Assessed through Bivalve Biomonitoring and Environmental Surveillance

The genetic diversity of Hepatitis A Virus (HAV) circulating in the Campania Region in years 2015&ndash;2018 was investigated through the monitoring of sentinel bivalve shellfish and water matrices. Overall, 463 water samples (71 sewage samples, 353 coastal discharge waters, and 39 seawaters samples), and 746 bivalve shellfish samples were analyzed. Positivity for HAV was detected in 20/71 sewage samples, 14/353 coastal discharge waters, 5/39 seawaters, and 102/746 bivalve shellfish. Sixty-one of the positive samples were successfully sequenced and were characterized as genotype IA (n = 50) and IB (n = 11). The prevalent strain circulating in 2015 in both bivalves and waters was the IA strain responsible for the outbreak occurring around the same time in the Naples area. This variant was no longer identified in subsequent years (2017&ndash;2018) when, instead, appeared two of the IA variants of the multistate outbreak affecting men who have sex with men (MSM), VRD_521_2016, and RIVM-HAV16&ndash;090, with the former prevailing in both shellfish and water environments. HAV IB isolates were detected over the years in shellfish and in water matrices, but not in clinical samples, suggesting that this genotype had been circulating silently. An integrated surveillance system (environment/food/clinical cases) can be a useful tool to monitor changes in viral variants in the population, as well as an early warning system