New flavonoids with multiple bronchodilator activity pathways from Tephrosia purpurea L. (Pers.) growing in Saudi Arabia.

Total extract of Tephrosia purpurea (T. purpurea) expressed potent ex-vivo bronchodilator effect in isolated Guinea pigs' tracheal muscles. Fractionation of T. purpurea total extract (TPTE) using liquid-liquid technique followed by ex-vivo bronchodilator testing indicated that the activity was trapped to the chloroform (CHCl3) soluble fraction. Phytochemical study of the CHCl3 fraction guided by ex-vivo bronchodilator activity led to the isolation of 7 active flavones of which compounds 1 (epi-Tephroapollin G), 3 (Acetyltephroapollin C), 4 (4''-Dehydroxytephroapollin E), and 5 (epi-Tephroapollin F) were new. Structures were identified using relevant spectroscopic tools including optical rotations and CD data. Compounds 1, 3, 4 and lanceolatin A (6) behaved like papaverine by inhibiting carbachol (CCh) as well as high potassium (K+)-mediated contractions at equivalent concentrations with varied potencies whereas (-)-Tephroapollin G (2) selectively inhibited CCh-mediated contractions but was not found active against high K+. epi-Tephroapollin F (5) and (-)-Pseudosemiglabrin (7) in contrast were significantly more potent to abolish CCh induced contraction when compared with high K+ similar to dicyclomine. Papaverine like dual phosphodiesterase enzyme Ca++ ion inhibitory activities of 1, 3, 4 and 6 were confirmed indirectly by the bolster of the isoprenaline curves against CCh to the left whereas Ca++ inhibitory effect of 1 and 3-7 was confirmed by the rightward deflection of Ca++ concentration-response curves (CRCs) towards right with quashing of the maximum response in same fashion like verapamil. Moreover, compounds 2, 5 and 7 at lower concentrations showed selective blockade of muscarinic receptor similar to atropine. Oral administration of the TPTE, CHCl3 and 7 to guinea pigs significantly protected against bronchospasm induced by 0.2 % histamine aerosol in vivo.

Pyrethroid-Induced Organ Toxicity and Anti-Oxidant-Supplemented Amelioration of Toxicity and Organ Damage: The Protective Roles of Ascorbic Acid and α-Tocopherol.

The pyrethroid toxicants, fatal at high doses, are found as remnants of crop pesticides and ingredients of commercially available insecticides. The toxic effects of high-content insecticidal pyrethroid formulations are available in 0.05 g, 1.17 g, and 0.04 g pyrethroid-instilled products, namely burning coils, pyrethroid-soaked mats, and liquid formulations of pyrethroids that release pyrethroid vapor/smoke upon heating. They provided 5.46 g/kg, 21.15 g/kg, and 4.24 g/kg of toxicants to the experimental animals over a total of 3 weeks/5 h per os (p.o.) administration, producing necrosis, hyperemia, and fatty changes in the liver; fiber separation in cardiac muscles; atrophy, lymphatic infiltration, blood vessel congestion, and hyperemia in the heart tissues of the experimental animals. The glomerular tuft necrosis, cytoplasmic degeneration of renal tubular cells, necrotic tubules, congestion, and dilatation of blood vessels were observed in the kidney tissue of intoxicated animals. Air-space enlargement, interstitial inflammation, lymphocyte infiltration aggregates, connective tissue infiltration by inflammatory cells, and hyperemia were found in the lung tissues. The pyrethroid toxicants also produced nervous tissue degeneration and decreased neurons in the brain, which were observed through histopathological examinations of the brain, lungs, heart, kidneys, and liver. The protective effects of ascorbic acid (AA/vitamin C) and α-tocopherol (E307/vitamin E) at 100 mg/kg oral doses administered daily for the entire period of the toxicant exposure of three weeks to the experimental mice, aged between 3-4 months and weighing ≈30 g, ameliorated the tissue damage, as observed through the histopathological examinations. The ascorbic acid caused recovery of the liver, kidney, brain, and heart tissue damage, while α-tocopherol was effective at ameliorating the damage in the kidneys and lung tissue compared with the control groups. The high levels of tissue damage recovery suggested a prophylactic effect of the concurrent use of ascorbic acid and α-tocopherol for the subjects under the exposure of pyrethroids.

Neutropenic Enterocolitis and Rapid Spontaneous Resolution of Portal Venous Gas: A Non-Respiratory Manifestation of COVID-19.

The COVID-19 pandemic is affecting millions across the globe. The population of immunosuppressed individuals are at greatest risk of morbidity and mortality. Data on COVID-19 induced illness in the immunocompromised host are sparse. We aim to highlight the possibility of atypical and non-respiratory presentations of COVID-19 (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) in immunosuppressed individuals as our case reveals a rare COVID-19 associated GI presentation of neutropenic enterocolitis with bloody diarrhea.

Precordial ECG Lead Mispositioning: Its Incidence and Estimated Cost to Healthcare.

BACKGROUND: The study was performed to estimate the incidence and economic burden of electrocardiogram (ECG) precordial lead mispositioning, in an effort to highlight the need for quality improvement. Lead mispositioning may result in further cardiovascular testing to rule out significant cardiac disease, thus adding to the national healthcare financial burden. METHODS: All consecutive adult ECGs done during 2018, were reviewed. ECGs with acute anterior myocardial infarction (AMI), bundle branch blocks, left ventricular hypertrophy (LVH), left anterior fascicular block (LAFB), pre-excitation, left axis deviation, ventricular pacing and low voltage QRS were excluded. Septal infarcts identified automatically by the computerized software or identified manually using the criteria of QS composite in V2 were not excluded. Computer interpreted ECGs as "cannot rule-out anterior infarct" were also not excluded from this data. Reimbursement of various stress test types was used to estimate the cost burden of misdiagnosed ECGs. RESULTS: A total of 9424 adult ECGs were evaluated. Poor R-wave progression (PRWP) or reversed R-wave progression (RRWP) accounted for 497 (5.27%) and 102 (1.08%) ECGs, respectively. A total of 335 septal infarct interpretations constituted about 3.55% of all ECGs. ECGs categorized as "cannot rule-out AMI" due to PRWP constituted about 0.89%. Therefore, a total of 1018 ECGs (10.8%) could be possibly falsely labelled as some type of myocardial infarction. CONCLUSION: Precordial ECG lead mispositioning can lead to significantly abnormal ECG patterns, leading to false diagnoses and further unnecessary cardiovascular testing. This not only increases risk and cost to the patient, but also adds to the national healthcare financial burden.

Atypical Manifestation of COVID-19-Induced Myocarditis.

We present a case of a 39-year-old male who presented with chest pain without fever or respiratory symptoms. Troponins were elevated and electrocardiogram (ECG) was inconclusive for ST-elevation myocardial infarction (STEMI). Angiography revealed normal coronaries and the patient was found to be coronavirus disease 2019 (COVID-19) positive; he was diagnosed with COVID-19 myocarditis. With the global pandemic, more cases are emerging regarding myocardial injury induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Although COVID-19 manifests primarily as respiratory disease, few cases of cardiac injury without respiratory involvement or febrile illness have been reported. This case illustrates that COVID-19 can present atypically and affect an isolated non-respiratory organ system.

Studies on the antihypertensive and antidyslipidemic activities of Viola odorata leaves extract.

BACKGROUND: This study was undertaken to provide pharmacological basis for the medicinal use of Viola odorata Linn. in hypertension and dyslipidemia using the in vivo and in vitro assays. RESULTS: Viola odorata leaves extract (Vo.Cr), which tested positive for alkaloids, saponins, tannins, phenolics, coumarins and flavonoids, caused a dose-dependent (0.1-1.0 mg/kg) decrease in mean arterial blood pressure in anaesthetized rats. In isolated guinea-pig atria, Vo.Cr equally inhibited force and rate of spontaneous atrial contractions. On the baseline of rat thoracic aortae (endothelium-intact and denuded), the plant extract caused phentolamine-sensitive vasoconstriction. When tested on phenylephrine (PE, 1 µM) and K(+) (80 mM)-induced vasoconstriction, Vo.Cr caused a concentration-dependent relaxation and also caused a rightward shift of Ca(++) concentration-response curves as well as suppression of PE (1 µM) control peaks in Ca(++)-free medium, similar to that caused by verapamil. In the presence of L-NAME, the relaxation curve of Vo.Cr was partially inhibited showing involvement of Nitric oxide (NO) mediated pathway. In Tyloxapol-induced dyslipidemia, Vo.Cr caused reduction in total cholesterol and triglyceride levels. In high-fat diet-induced dyslipidemia model, the plant extract caused a significant decrease in total cholesterol, LDL-C, atherogenic index and prevented the increase in average body weights, while it increased HDL-C. CONCLUSIONS: These data indicate that the vasodilator effect of the plant extract is mediated through multiple pathways like inhibition of Ca(++) influx via membranous Ca(++) channels, its release from intracellular stores and NO-mediated pathways, which possibly explain the fall in BP. The plant also showed reduction in body weight and antidyslipidemic effect which may be due to the inhibition of synthesis and absorption of lipids and antioxidant activities. Thus, this study provides a pharmacologic rationale to the medicinal use of Viola odorata in hypertension and dyslipidemia.

Chemical constituents of Nepeta distans.

Phytochemical investigation of Nepeta distans Raul resulted in the isolation of a new phenolic compound, nepatanol (1), and eight known compounds, markhamioside F, netidiol, nepedinol, thymoquinone, eugenol, oleanolic acid, ursolic acid, and beta-sitosterol, which have been isolated for the first time from this source. Structures of all the isolates were established on the basis of MS, and 1D and 2D NMR spectral data and by comparison with reported data.