SARS-CoV-2 omicron variants are susceptible in vitro to Artemisia annua hot water extracts.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia annua L. has >2000 yr of history in treating fever a symptom common to many infectious diseases including viruses. The plant is widely used as a tea infusion in many areas of the globe to thwart many infectious diseases. AIM OF THE STUDY: The SARS-CoV-2 (COVID-19) virus continues to infect millions while rapidly evolving new variants that are more transmissible and evade vaccine-elicited antibodies, e.g., omicron and its subvariants. Having shown potency against all previously tested variants, A. annua L. extracts were further tested against highly infectious omicron and its recent subvariants. MATERIALS AND METHODS: Using Vero E6 cells, we measured the in vitro efficacy (IC50) of stored (frozen) dried-leaf hot-water A. annua L. extracts of four cultivars (A3, BUR, MED, and SAM) against SARS-CoV-2 variants: original WA1 (WT), BA.1 (omicron), BA.2, BA.2.12.1, and BA.4. End point virus titers of infectivity in cv. BUR-treated human lung A459 cells overexpressing hu-ACE2 were determined for both WA1 and BA.4 viruses. RESULTS: When normalized to the artemisinin (ART) or leaf dry weight (DW) equivalent of the extract, the IC50 values ranged from 0.5 to 16.5 µM ART and from 20 to 106 µg DW. IC50 values were within limits of assay variation of our earlier studies. End-point titers confirmed a dose-response inhibition in ACE2 overexpressing human lung cells to the BUR cultivar. Cell viability losses were not measurable at leaf dry weights ≤50 µg for any cultivar extract. CONCLUSIONS: A. annua hot-water extracts (tea infusions) continue to show efficacy against SARS-CoV-2 and its rapidly evolving variants and deserve greater attention as a possible cost-effective therapeutic.

SARS-CoV-2 omicron variants succumb in vitro to Artemisia annua hot water extracts.

The SARS-CoV-2 (COVID-19) global pandemic continuous to infect and kill millions while rapidly evolving new variants that are more transmissible and evading vaccine-elicited antibodies. Artemisia annua L. extracts have shown potency against all previously tested variants. Here we further queried extract efficacy against omicron and its recent subvariants. Using Vero E6 cells, we measured the in vitro efficacy (IC 50 ) of stored (frozen) dried-leaf hot-water A. annua L. extracts of four cultivars (A3, BUR, MED, and SAM) against SARS-CoV-2 variants: original WA1 (WT), BA.1.1.529+R346K (omicron), BA.2, BA.2.12.1, and BA.4. IC 50 values normalized to the extract artemisinin (ART) content ranged from 0.5-16.5 µM ART. When normalized to dry mass of the extracted A. annua leaves, values ranged from 20-106 µg. Although IC 50 values for these new variants are slightly higher than those reported for previously tested variants, they were within limits of assay variation. There was no measurable loss of cell viability at leaf dry weights ≤50 µg of any cultivar extract. Results continue to indicate that oral consumption of A. annua hot-water extracts (tea infusions) could potentially provide a cost-effective approach to help stave off this pandemic virus and its rapidly evolving variants.

Surge in the jellyfish population of a tropical monsoonal estuary: A boon or bane to its plankton community dynamics?

Recurrent jellyfish blooms and their impacts on ecosystem deliverables of coastal habitats have become a major ecological concern. In view of this, repercussions of a surge in the jellyfish population on the plankton community were studied in Cochin estuary (CE), the largest tropical estuary along the southwest coast of India. Evaluation of hydrographic attributes and plankton community of the CE during early and late pre-monsoon revealed a marked disparity in its hydrography which favoured an increase in jellyfish abundances during late pre-monsoon, eliciting distinct impacts on the plankton community. The escalation in the jellyfish abundance and their subsequent predation on the crustacean plankton released the phytoplankton community from the grazing pressure resulting in a trophic cascade in the planktonic food web. The indiscriminate feeding of jellyfishes on the ichthyoplankton, decapod larvae, and Copepoda, the primary diet component of forage fishes evoked a potent threat to the fishery potential of CE.

Artemisia annua L. hot-water extracts show potent activity in vitro against Covid-19 variants including delta.

ETHNOPHARMACOLOGICAL RELEVANCE: For millennia, Artemisia annua L. was used in Southeast Asia to treat "fever". This medicinal plant is effective against multiple pathogens and is used by many global communities as a source of artemisinin derivatives that are first-line drugs to treat malaria caused by Plasmodium parasites. AIM OF THE STUDY: The SARS-CoV-2 (Covid-19) global pandemic has killed millions and evolved numerous variants, with delta being the most transmissible to date and causing break-through infections of vaccinated individuals. We further queried the efficacy of A. annua cultivars against new variants. MATERIALS AND METHODS: Using Vero E6 cells, we measured anti-SARS-CoV-2 activity of dried-leaf hot-water A. annua L. extracts of four cultivars, A3, BUR, MED, and SAM, to determine their efficacy against five infectious variants of the virus: alpha (B.1.1.7), beta (B.1.351), gamma (P.1), delta (B.1.617.2), and kappa (B.1.617.1). RESULTS: In addition to being effective against the original wild type (WT) WA1, A. annua cultivars A3, BUR, MED, and SAM were also potent against all five variants. IC50 and IC90 values based on measured artemisinin content ranged from 0.3 to 8.4 µM and 1.4-25.0 µM, respectively. The IC50 and IC90 values based on dried leaf weight (DW) used to make the tea infusions ranged from 11.0 to 67.7 µg DW and 59.5-160.6 µg DW, respectively. Cell toxicity was insignificant at a leaf dry weight of ≤50 µg in the extract of any cultivar. CONCLUSIONS: Results suggest that oral consumption of A. annua hot-water extracts (tea infusions) could potentially provide a cost-effective therapy to help stave off the rapid global spread of these variants, buying time for broader implementation of vaccines.

Artemisia annua L. extracts inhibit the in vitro replication of SARS-CoV-2 and two of its variants.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia annua L. has been used for millennia in Southeast Asia to treat "fever". Many infectious microbial and viral diseases have been shown to respond to A. annua and communities around the world use the plant as a medicinal tea, especially for treating malaria. AIM OF THE STUDY: SARS-CoV-2 (the cause of Covid-19) globally has infected and killed millions of people. Because of the broad-spectrum antiviral activity of artemisinin that includes blockade of SARS-CoV-1, we queried whether A. annua suppressed SARS-CoV-2. MATERIALS AND METHODS: Using Vero E6 and Calu-3 cells, we measured anti SARS-CoV-2 activity against fully infectious virus of dried leaf extracts of seven cultivars of A. annua sourced from four continents. IC50s were calculated and defined as the concentrations that inhibited viral replication by 50%; CC50s were also calculated and defined as the concentrations that kill 50% of cells. RESULTS: Hot-water leaf extracts based on artemisinin, total flavonoids, or dry leaf mass showed antiviral activity with IC50 values of 0.1-8.7 µM, 0.01-0.14 µg, and 23.4-57.4 µg, respectively. Antiviral efficacy did not correlate with artemisinin or total flavonoid contents of the extracts. One dried leaf sample was >12 years old, yet its hot-water extract was still found to be active. The UK and South African variants, B1.1.7 and B1.351, were similarly inhibited. While all hot water extracts were effective, concentrations of artemisinin and total flavonoids varied by nearly 100-fold in the extracts. Artemisinin alone showed an estimated IC50 of about 70 µM, and the clinically used artemisinin derivatives artesunate, artemether, and dihydroartemisinin were ineffective or cytotoxic at elevated micromolar concentrations. In contrast, the antimalarial drug amodiaquine had an IC50 = 5.8 µM. Extracts had minimal effects on infection of Vero E6 or Calu-3 cells by a reporter virus pseudotyped by the SARS-CoV-2 spike protein. There was no cytotoxicity within an order of magnitude above the antiviral IC90 values. CONCLUSIONS: A. annua extracts inhibit SARS-CoV-2 infection, and the active component(s) in the extracts is likely something besides artemisinin or a combination of components that block virus infection at a step downstream of virus entry. Further studies will determine in vivo efficacy to assess whether A. annua might provide a cost-effective therapeutic to treat SARS-CoV-2 infections.

Artemisia annua L. extracts inhibit the in vitro replication of SARS-CoV-2 and two of its variants.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia annua L. has been used for millennia in Southeast Asia to treat "fever". Many infectious microbial and viral diseases have been shown to respond to A. annua and communities around the world use the plant as a medicinal tea, especially for treating malaria. AIM OF THE STUDY: SARS-CoV-2 (the cause of Covid-19) globally has infected and killed millions of people. Because of the broad-spectrum antiviral activity of artemisinin that includes blockade of SARS-CoV-1, we queried whether A. annua suppressed SARS-CoV-2. MATERIALS AND METHODS: Using Vero E6 and Calu-3 cells, we measured anti viral activity SARS-CoV-2 activity against fully infectious virusof dried leaf extracts of seven cultivars of A. annua sourced from four continents. IC50s were calculated and defined as (the concentrations that inhibited viral replication by 50%.) and CC50s (the concentrations that kill 50% of cells) were calculated. RESULTS: Hot-water leaf extracts based on artemisinin, total flavonoids, or dry leaf mass showed antiviral activity with IC50 values of 0.1-8.7 µM, 0.01-0.14 µg, and 23.4-57.4 µg, respectively. Antiviral efficacy did not correlate with artemisinin or total flavonoid contents of the extracts. One dried leaf sample was >12 years old, yet the hot-water extract was still found to be active. The UK and South African variants, B1.1.7 and B1.351, were similarly inhibited. While all hot water extracts were effective, concentrations of artemisinin and total flavonoids varied by nearly 100-fold in the extracts. Artemisinin alone showed an estimated IC50 of about 70 µM, and the clinically used artemisinin derivatives artesunate, artemether, and dihydroartemisinin were ineffective or cytotoxic at elevated micromolar concentrations. In contrast, the antimalarial drug amodiaquine had an IC50 = 5.8 µM. Extracts had minimal effects on infection of Vero E6 or Calu-3 cells by a reporter virus pseudotyped by the SARS-CoV-2 spike protein. There was no cytotoxicity within an order of magnitude above the antiviral IC90 values. CONCLUSIONS: A. annua extracts inhibit SARS-CoV-2 infection, and the active component(s) in the extracts is likely something besides artemisinin or a combination of components that block virus infection at a step downstream of virus entry. Further studies will determine in vivo efficacy to assess whether A. annua might provide a cost-effective therapeutic to treat SARS-CoV-2 infections.

Use of the surgical Apgar score to guide postoperative care.

INTRODUCTION: The surgical Apgar score (SAS) can predict 30-day major complications or death after surgery. Studies have validated the score in different patient populations and suggest it should be used to objectively guide postoperative care. We aimed to see whether using the SAS in a decisive approach in a future randomised controlled trial (RCT) would be likely to demonstrate an effect on postoperative care and clinical outcome. METHODS: A total of 143 adults undergoing general/vascular surgery in 9 National Health Service hospitals were recruited to a pilot single blinded RCT and the data for 139 of these were analysed. Participants were randomised to a control group with standard postoperative care or to an intervention group with care influenced (but not mandated) by the SAS (decisive approach). The notional primary outcome was 30-day major complications or death. RESULTS: Incidence of major complications was similar in both groups (control: 20/69 [29%], intervention: 23/70 [33%], p=0.622). Immediate admissions to the critical care unit was higher in the intervention group, especially in the SAS 0-4 subgroup (4/6 vs 2/7) although this was not statistically significant (p=0.310). Validity was also confirmed in area under the curve (AUC) analysis (AUC: 0.77). CONCLUSIONS: This pilot study found that a future RCT to investigate the effect of using the SAS in a decisive approach may demonstrate a difference in postoperative care. However, significant changes to the design are needed if differences in clinical outcome are to be achieved reliably. These would include a wider array of postoperative interventions implemented using a quality improvement approach in a stepped wedge cluster design with blinded collection of outcome data.

Appendicular abscess with appendicolith in a Spigelian hernia masquerading caecal volvulus-A case report.

INTRODUCTION: Spigelian hernias are rare hernias of the anterior abdominal wall named after Adrian van den Spiegel, the anatomist who first described them in the 16th century. They represent around 2% of all hernias. PRESENTATION OF CASE: We present an 83-year-old female with one week history of a painful right iliac fossa swelling, her examination revealed a tender lump with no cough impulse and non-reducible and her computed tomography (CT) scan showed a mass anterior to ileocaecal valve suggestive of a caecal volvulus. Intra-operative the finding was a Spigelian hernia containing an appendicular abscess and an appendicolith. DISCUSSION: The diagnosis of Spigelian hernias represents a challenge for the surgeons principally due to their rarity but also due to their anatomy and the variety of their contents. Searching the literature we found many different intra-abdominal structures presenting within a Spigelian hernia but we did not encounter a case similar to this. CONCLUSION: Clinicians need to be aware of these hernias when dealing with lower abdominal swellings and have a high index of suspicion even in the presence of negative clinical and CT findings.

Computed tomography findings of bowel wall thickening: its significance and relationship to endoscopic abnormalities.

INTRODUCTION: The aim of this study was to conduct retrospective analysis of abdominopelvic computed tomography (CT) reports, identifying those patients in whom bowel wall thickening (BWT) was observed, and to correlate these reports with subsequent endoscopic evaluation. METHODS: Formal reports for all patients undergoing abdominopelvic CT between February 2007 and September 2009 were reviewed. Where patients were identified as having colorectal 'wall thickening', results of subsequent endoscopic evaluations were documented. Only those patients with a report of BWT who had follow-up endoscopy (colonoscopy, sigmoidoscopy) were included in the analysis. RESULTS: A total of 165 patients were included. Abnormalities on endoscopy at the exact site of the BWT on CT were found in 95 patients (57.58%); in 36 cases (21.82%) this was a malignant lesion. BWT of the transverse colon was significantly more likely to correspond to an endoscopic finding of cancer than other sites (p=0.034). Rectal bleeding was reported significantly more often in patients with BWT and neoplastic disease on endoscopy compared with those with normal endoscopy (p=0.04). Excluding patients with inflammatory/diverticular lesions, 59.02% of Caucasians had a neoplastic lesion at the site of reported BWT, significantly higher than the other ethnic groups (p=0.008). There were 38 patients (23.03%) who did not present with bowel symptoms and, of these, 6 were diagnosed subsequently with colorectal cancer. CONCLUSIONS: This study supports endoscopic evaluation to investigate patients with CT evidence of BWT, especially in cases involving the transverse colon, in Caucasian patients or in association with symptoms of rectal bleeding.

Incarcerated inguinal hernia: atypical presentation of an abdominal aortic aneurysm.

The diagnosis of an inguinal hernia, be it complicated or uncomplicated, is often simple and straight forward. Rarely, this simple presentation may be the external manifestation of a distant pathology, which is in communication with the inguinal canal through its anatomic relationship. We report a case of ruptured abdominal aortic aneurysm (AAA) that presented as a strangulated left inguinal hernia. To the best of our knowledge, this is the first reported case where the patient was stable on initial presentation, both clinically and biochemically. The only clue for our patient that pointed towards a potential aneurysm was the presence of intra-operative blood in the spermatic cord. We conclude that any patient presenting with symptoms suggestive of a hernia, particularly on the left side, should have a thorough assessment to rule out AAA.

Cervical cancer in women aged less than 25: East Kent experience.

The National Health Service Cervical Screening Programme (NHSCSP) guidelines raised the initiation of screening age from 20 to 25 years of age in 2004, on the basis that only 1.3% of cervical cancers occur in this age group. Between 2003 and 2005, cervical cancer was diagnosed in six women under 25 years in East Kent, 6.25% of 96 cervical cancers cases. All except one patient in our series presented with a cervical smear abnormality. High-grade cervical smear abnormalities were identified and treated in 187 women under 25 years during this period. Adoption of the guidelines may increase the incidence of invasive disease in young women, the stage at diagnosis and radicality of treatment required.

Triterpenoids from Dysoxylum malabaricum.

Two triterpenes 21R,23R-epoxy-21alpha-ethoxy-24S,25-dihydroxyapotirucall-7-en-3-one and 24R-acetoxy-3beta,25-dihydroxycycloartane were isolated from the leaves of Dysoxylum malabaricum together with eight known compounds lupeone, lupeol. sitosterol, dipterocarpol, cycloart-25-ene-3beta,24-diol, 24R,25-dihydroxycycloartan-3-one, 3beta,24R,25-trihydroxycycloartane and ergosta-5,24(24(1))-diene-3beta,4beta,20S-triol. The complete 1H and 13C NMR spectral assignment of the new apotirucallene triterpenoid has been achieved by 1H-1H COSY, HMQC and HMBC experiments.

Carcinoma gall bladder presenting as hemobilia.

A 60-year-old man presented with recurrent bouts of melena, requiring multiple transfusions. Upper GI endoscopic evaluation demonstrated fresh bleeding from the ampulla of Vater. Ultrasonography and CT scan suggested a gall bladder mass without evidence of metastases. Laparotomy confirmed a mass confined to the lumen of the gall bladder. The patient underwent cholecystectomy. Histological examination showed papillary adenocarcinoma of the gall bladder extending up to the muscularis propria.

Electrical impedance cardiography using artificial neural networks.

This study evaluates the use of artificial neural networks to estimate stroke volume from pre-processed, thoracic impedance plethysmograph signals from 20 healthy subjects. Standard back-propagation was used to train the networks, with Doppler stroke volume estimates as the desired output. The trained networks were then compared to two classical biophysical approaches. The coefficient of determination (R2 x 100%) between the biophysical approaches and the Doppler was 8.20% and 9.90%, while it was 77.38% between the best neural network and the Doppler. Among these methods, only the neural network residuals had a significant zero mean Gaussian distribution (alpha=0.05). Our results indicate that an invertible relationship may exist between thoracic bioimpedance and stroke volume, and that artificial neural networks may offer a potentially advantageous approach for estimating stroke volume from thoracic electrical impedance, both because of their ease of use and their lack of confounding assumptions.

Mixed ligand complexes involving sulphur containing ligands--Part II. Ternary complexes of Zn(II) involving L-cysteine/D-penicillamine/L-cysteic acid and imidazoles.

The chemical equilibria involved in nine mixed ligand systems Zn(II)-L-cysteine (Cys)/D-penicillamine(Pen)/L-cysteic acid(Cya)(A)-imidazole(Him), histamine(Hist) and L-histidine(His)(B) have been investigated in aqueous perchlorate medium by pH titrimetry at 37 degrees and ionic strength, I = 0.15M (NaClO(4)). The mixed ligand complex species of the types ZnABH(2), ZnABH, ZnAB or ZnAB(2) have been detected in addition to various binary species due to ligands A and B. The results obtained for the ZnABH type of species indicate that the site of protonation is the amino group of Cys/Pen ligands in the Zn(II)-Cys/Pen(A)-Him, Hist and His(B) systems, and the amino group of Hist/His secondary ligands in the Zn(II)-Cya(A)-Hist and His(B) systems. In the ZnABH(2) type of species, one proton is attached with the primary ligand (A) and the other with the secondary ligand(B). In both ZnAB and ZnAB(2) type ternary species in all the systems, the primary ligand binds the metal in a bidentate manner and the secondary ligands Him, Hist and His bind the metal, respectively in a uni, bi and terdentate manner.

Bioconversion of arteannuin B to artemisinin.

Arteannuin B, which co-occurs with artemisinin, the potent antimalarial principle of the Chinese medicinal herb Artemisia annua (Asteraceae), has been converted to the latter using crude and semi-purified cell-free extracts of the leaf homogenates of the plant. Detection procedures to quantitate this bioconversion, including one that is novel which uses gcms, are detailed.

STUDIES ON 15(S)15 METHYL PGF2α BY INTRAMUSCULAR ROUTE FOR SECOND TRIMESTER ABORTION (TWO HOURLY SCHEDULE).

A multicentre study was undertaken to study intramuscular 15(S)15 methyl PGF2α (Prostin 15M, Upjohn) for induction of second trimester abortion. The patients were premedicated with Imodium and Perinorm to control the gastrointestinal side effects. The dose of Prostin 15M was 250 µg every two hours and the progress of the abortion was assessed before each injection. If there was no progress at the end of 10 injections the case was classified as a failure. Ninety-seven patients were recruited for the study, 39 were primigravidae and 58 multigravidae. Twenty-four out of 39 primigravidae and 52 out of 58 multigravidae aborted with the treatment. The mean induction abortion interval was 17.8 hours in the primigravidae and 14.5 hours in the multigravidae patients. The mean number of episodes of vomiting was 2.9 and diarrhoea 4.2 per patient per trial. The primigravidae had slightly higher incidence of gastrointestinal side effects. The overall incidence of incomplete abortion was 17.1%.

A non-proteinaceous toxin from the venomous spines of the lionfish Pterois volitans (Linnaeus).

The venomous spines of P. volitans contain a non-proteinaceous ichthyotoxin of low molecular weight. This toxin could be isolated only from spines excised from the living fish; the toxin is apparently destroyed following death, as the extracts of the spines of the dead fish were non-toxic.