Coronavirus disease 2019 (COVID-19), human erythrocytes and the PKC-alpha/-beta inhibitor chelerythrine -possible therapeutic implication.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19. Until now, diverse drugs have been used for the treatment of COVID-19. These drugs are associated with severe side effects, e.g. induction of erythrocyte death, named eryptosis. This massively affects the oxygen (O2) supply of the organism. Therefore, three elementary aspects should be considered simultaneously: (1) a potential drug should directly attack the virus, (2) eliminate virus-infected host cells and (3) preserve erythrocyte survival and functionality. It is known that PKC-α inhibition enhances the vitality of human erythrocytes, while it dose-dependently activates the apoptosis machinery in nucleated cells. Thus, the use of chelerythrine as a specific PKC-alpha and -beta (PKC-α/-ß) inhibitor should be a promising approach to treat people infected with SARS-CoV-2.

Facial eschar following a single application of black salve.

A previously healthy 86-year-old male was transported by ambulance to the trauma bay of the emergency department (ED) for profuse bleeding from the left temple. The ambulance crew raised concern that the volume and force of the bleed may suggest arterial involvement. The patient reported having applied a natural topical remedy to a mole two weeks prior at the recommendation of a naturopath. The patient described progressive blackening and swelling of the area in the days following the single application of the product. After gaining control of the bleeding in the ED, the area was found to have a raised, 2 cm eschar.

Identification of metabolites of selected benzophenanthridine alkaloids and their toxicity evaluation.

Selected benzo[c]phenathridine alkaloids were biotransformed using rat liver microsomes and identified by liquid chromatography and mass spectrometry. While the metabolites of commercially available sanguinarine and chelerythrine have been studied in detail, data about the metabolism of the minor alkaloids remained unknown. Reactions involved in transformation include single and/or double O-demethylation, demethylenation, reduction, and hydroxylation. Two metabolites, when isolated, purified and tested for toxicity, were found to be less toxic than the original compounds.

Sanguinarine suppresses basal-like breast cancer growth through dihydrofolate reductase inhibition.

Basal-like breast cancer (BLBC) remains a great challenge because of its clinically aggressive nature and lack of effective targeted therapy. We analyzed the potential anti-neoplastic effects of sanguinarine, a natural benzophenanthridine alkaloid, against BLBC cells. Sanguinarine treatment resulted in a reduction of cell migration, in a dose-dependent inhibition of cell viability and in the induction of cell death by apoptosis in both human (MDA-MB-231 cells) and mouse (A17 cells) in vitro models of BLBC. In vivo experiments demonstrated that oral administration of sanguinarine reduced the development and growth of A17 transplantable tumors in FVB syngeneic mice. Western blotting analysis revealed that suppression of BLBC growth by sanguinarine was correlated with a concurrent upregulation of p27 and downregulation of cyclin D1 and with the inhibition of STAT3 activation. In addition, we identified sanguinarine as a potent inhibitor of dihydrofolate reductase (DHFR), able to impair enzyme activity even in methotrexate resistant MDA-MB-231 cells. These results provide evidence that sanguinarine is a promising anticancer drug for the treatment of BLBC.

Protective effect of topical application of α-tocopherol and/or N-acetyl cysteine on argemone oil/alkaloid-induced skin tumorigenesis in mice.

Since bioantioxidants in plasma of Epidemic Dropsy patients [a condition caused by consumption of adulterated mustard oil with argemone oil (AO)] were found to be significantly decreased, the beneficial effect of N-acetyl cysteine (NAC) and α-tocopherol (TOCO) against AO- or sanguinarine (SANG)-induced tumorigenicity was undertaken in mice. Topical application of TOCO and NAC either alone or in combination showed significant protection against AO/TPA- and SANG/TPA-induced skin tumorigenicity. Histopathological findings suggest that papillomatous growth in AO/TPA- and SANG/TPA-treated animals were substantially protected following topical application of TOCO or NAC. Further, treatment of TOCO and NAC either alone or in combination to AO/TPA- or SANG/TPA-induced mice significantly decreased lipid peroxidation, along with significant revival in glutathione (GSH) content and activities of tyrosinase, histidase, catalase, SOD, GSH peroxidase, and GSH reductase in skin. In vitro studies showed that TOCO and/or NAC significantly decreased the AO and SANG induced cell proliferation and activation of ERK, p38, JNK MAPKs and NF-κB signaling in HaCaT cells. In summary, TOCO and NAC may be useful in preventing the tumorigenic response of AO and SANG probably by acting as scavenger of free radicals and inhibiting MAPKs and NF-κB signaling.

The staining potential of various currently marketed mouthrinses.

OBJECTIVES: The objectives of this clinical trial were to determine the tooth staining potential as measured by the Macpherson Modification of the Lobene Stain Index, and degree of taste alteration of four currently marketed mouthrinses when used over a 12-week period. METHODS: This investigation consisted of a 12-week, observer-blind, single-center, randomized comparison of five parallel groups of subjects. One-hundred and seventy-one subjects granting their informed consent completed the trial. Subjects were randomized to one of four currently marketed mouthrinses Crest PRO-HEALTH Rinse (CPH), Cepacol (C), Scope (S), Viadent ADVANCED CARE (V), or brushing alone (BA) with a currently marketed fluoride toothpaste. Upon randomization, subjects received a baseline stain score and then a prophylaxis to remove all extrinsic stain. Clinical assessments were repeated after six weeks and three months of product use, and subjects were asked to complete a questionnaire after the first use, at day 4, day 14, at six weeks, and 12 weeks to assess potential taste alteration. RESULTS: CPH and C demonstrated significantly (p < 0.001) more extrinsic stain after six weeks of use, and CPH, C (p < 0.001), and S (p = 0.01) after 12 weeks of use versus brushing alone with fluoride toothpaste. V was not significantly different from brushing alone at either time point. After six weeks of using the product as directed, up to 53% of subjects using CPH experienced taste interference for up to three hours post-rinse. CONCLUSIONS: The results of this study demonstrated that regular use of CPH and C mouthrinses resulted in extrinsic stain accumulation after six weeks, with increased accumulation after 12 weeks versus brushing alone.

Outbreak of epidemic dropsy in Ethiopia: the clinical and therapeutic observation.

INTRODUCTION: Epidemic dropsy results from ingestion of argemone oil contaminated food staffs. The oil from Argemone Mexican seeds contains toxic alkaloids called sanguinarine and dehydrosangunarine. These cause wide spread capillary dilatation, proliferation and leakages. This leads to oedema, hypovolemia and hypotension. OBJECTIVE: To describe the socio-demographic and clinical manifestations of the patients affected with epidemic dropsy in Tikur Anbessa specialized Hospital (TASH). METHODS: A case series study was conducted in an outbreak with unusual cases which was later diagnosed to be epidemic dropsy. Clinical evaluation of suspects was done and optimal therapy given for the complications detected and information was filled in structured format by medical residents and medial chart records review was made for occurrence of new complications in the end of 9 months. RESULTS: A total of 164 patients were seen at TASH from 26 households, in 8 sub-cities of Addis Ababa. A wide range of age group was affected with 70% from 16 to 40 years of age. There was no case among less than 5 years of age. Females were affected more than threefold as compared to males. All the patients manifested with bilateral leg swelling and pitting oedema. It was tender in 50 (30.4%) of them while 43 (26.2%) had erythema. Tachycardia was the next common manifestation occurring in 135 (82.3%), followed by cough in 123 (75%), anaemia in 59 (36%), headache in 58 (35.4%), shortness of breathing in 52 (31.2%), hair loss in 44 (26.8%) and respiratory distress in 35 (21.3%). Abdominal pain, hepatomegally, nausea and vomiting were also seen. There was abnormality in the chest X-ray of 31 (27.2%). Hair loss, tingling and burning extremities, difficulty of standing, hyperpigmentation, pruritic rash and eye symptoms were observed lately during follow up. Five of the patients died while in hospital care due to acute respiratory distress syndrome (ARDS). CONCLUSIONS: The commonest clinical manifestation in our patients is bilateral leg swelling which is similar to other outbreaks of epidemic dropsy elsewhere. The mortality rate is also comparable with other series but all cases died by ARDS in our series which is unusual in other reports. As this is the first reported epidemics in Ethiopia the findings will create awareness of clinical features of epidemic dropsy among clinicians, and therefore, helps for diagnoses of similar problems in the future.

Outbreak investigation of epidemic dropsy in Addis Ababa, Ethiopia:.

BACKGROUND: A 17 year old female patient who presented to a tertiary Hospital in Addis Ababa with bilateral painful leg swelling of two months and shortness of breath, associated with cough and haemoptysis of one week duration was reported to the Ministry of Health and the Addis Ababa Health Bureau. The condition was later detected in 18 individuals from 4 households indicating occurrence of an outbreak of unknown cause in Addis Ababa which lasted during May-July 2008. OBJECTIVE: An outbreak investigation was initiated to identify the cause and prevent further spread, morbidity and mortality. METHODS: Using semi-structured questionnaire, quantitative assessment involving individual cases and affected households was conducted to detect aetiology and risk factors. Unaffected households as well as unaffected members of affected households were also included for comparison purpose. Record review of patients visiting hospitals was also done. Data were collected through house to house visits, and using interview of cases admitted to hospital. Samples of cooking oil were collected for laboratory testing. Data analysis was done using SPSS. RESULTS: A total of 182 patients, 50 (27.5%) males and 132 (72.5%) females, were identified till the outbreak was controlled fully. Age varied from 6-90 years. Death was confirmed in 12 cases, 8 of whom were female. The majority of the patients came from the adjoining Lideta (39.0%) and Kolfe Keranyo (31.9%) subcities. History of illness ranged from less than a week to 12 weeks before presentation. Out of the 106 household members of the 24 affected households identified during the first phase of the investigation, 83 were affected. Most family members who infrequently take meals at home, and children aged 3 years and below were spared. The 21 visited affected households from Kolfe keranyo, Lideta and Bole subcities bought cooking oil produced by a firm in Lideta subcity and all had bought their last supplies in March and April 2008. Samples of cooking food oil taken from this firm and from the affected households were found to have alkaloids of Argemone Mexicana. The number of new cases dropped to zero within 6 weeks after the source was closed. CONCLUSION: The occurrence of bilateral leg swelling in more than one family member of affected households, that bought cooking oil from the same source, sparing the toddlers, and those who infrequently take meals at home, further strengthened by laboratory confirmation of presence of argemone alkaloids in the cooking oil samples taken from the affected households and the common sources led to the diagnosis of the outbreak to be epidemic dropsy.

Laboratory investigation of epidemic dropsy in Addis Ababa, Ethiopia.

BACKGROUND: Food adulteration including adulteration of edible oils may cause serious health problems. One of the most common edible adulterants is argemone oil. An outbreak of epidemic dropsy occurred in Addis Ababa during May-June, 2008. One hundred and eighty two cases were recorded with twelve confirmed deaths. Dietary history of the cases revealed that vegetable oils were the usual cooking medium. OBJECTIVE: The aim of the study was hence to investigate the causes of this outbreak. METHODS: Contaminant identification was done using standard chemical tests, complemented with TLC. Toxicity study was done using Swiss albino mice feed with contaminated and non contaminated standard diet for 30 days. RESULTS: Laboratory investigation of the edible oils has indicated that 47 of the 280 edible oils analyzed were adulterated with argemone oil. About 81% of the edible oil samples collected from Lideta sub-city were adulterated with argemone oil. Toxicological investigation of the adulterated oils also indicated typical features of argemone alkaloid poisoning in mice. CONCLUSION: Results of both laboratory analysis and toxicological studies confirmed consumption of edible oils adulterated with argemone oil as the cause of epidemic dropsy in Addis Ababa.

Epidemic dropsy: case report and the morphologic features in a patient who died at Tikur Anbessa Specialized Hospital.

Epidemic dropsy results from the consumption of edible oils adulterated with argemone mexicana oil. In a 2008 epidemic in Addis Ababa five patients died and in one of these a partial autopsy has been performed. The clinical impression of acute respiratory distress syndrome has been confirmed by the demonstration of massive diffuse alveolar damage. These features are consistent with findings reported in similar epidemics.

Rise and fall of oral health products with Canadian bloodroot extract.

The rhizome of Sanguinaria canadensis (SC, bloodroot) contains an active principle with antimicrobial, antiinflammatory, antioxidative and immunomodulatory effects. For this reason SC extract has been added to toothpastes and mouthwashes in various concentrations. When tested separately, neither the toothpastes nor the mouthwashes with SC extract had any demonstrable clinical effectiveness against dental plaque and gingivitis. Although using them together twice a day seemed more effective than using placebo, more recent studies have shown conflicting results. Preclinical safety studies up to 2000, which did not include studies longer than 6 months, were thought not to indicate any appreciable potential for harm - to the oral mucosa in particular. In 2003, the FDA Subcommittee on Oral Health Care Drug Products for Over-the-Counter Human Use concluded from a review that using SC-containing products is safe. However, for reasons unknown, the review failed to consider publications between 1999 and 2001 that suggested a possible link between the use of SC-containing products and the pre-neoplastic lesion, leukoplakia. As it happened, bloodroot had already been removed (in 2001) from the formula of one of the most widely used products in question and the brand has since then disappeared altogether from the worldwide market.

PKC blockade differentially affects aversive but not appetitive gustatory memories.

After consumption of a new taste, there are mainly two possible outcomes for the establishment of a taste memory, either it will be aversive or safe depending on the consequences of taste consumption. It has been proposed that both types of learning share a common initial taste memory trace, which will lead to two different memory traces, safe or aversive. To study the role of PKC activity in aversive or safe taste memory formation, we administered chelerythrine, a PKC inhibitor, into the insular cortex or parietal cortex 20 min before conditioned taste aversion or attenuation of neophobia training. The results suggest that PKC activity is needed in the insular cortex for the establishment of aversive taste memory, but not for safe taste memory.