Potentiating Biosynthesis of Alkaloids and Polyphenolic Substances in Catharanthus roseus Plant Using ĸ-Carrageenan.

Catharanthus roseus is a medicinal plant that produces indole alkaloids, which are utilized in anticancer therapy. Vinblastine and vincristine, two commercially important antineoplastic alkaloids, are mostly found in the leaves of Catharanthus roseus. ĸ-carrageenan has been proven as plant growth promoting substance for a number of medicinal and agricultural plants. Considering the importance of ĸ-carrageenan as a promoter of plant growth and phytochemical constituents, especially alkaloids production in Catharanthus roseus, an experiment was carried out to explore the effect of ĸ-carrageenan on the plant growth, phytochemicals content, pigments content, and production of antitumor alkaloids in Catharanthus roseus after planting. Foliar application of ĸ-carrageenan (at 0, 400, 600 and 800 ppm) significantly improved the performance of Catharanthus roseus. Phytochemical analysis involved determining the amount of total phenolics (TP), flavonoids (F), free amino acids (FAA), alkaloids (TAC) and pigments contents by spectrophotometer, minerals by ICP, amino acids, phenolic compounds and alkaloids (Vincamine, Catharanthine, Vincracine (Vincristine), and vinblastine) analysis uses HPLC. The results indicated that all examined ĸ-carrageenan treatments led to a significant (p ≤ 0.05) increase in growth parameters compared to the untreated plants. Phytochemical examination indicates that the spray of ĸ-carrageenan at 800 mg L-1 increased the yield of alkaloids (Vincamine, Catharanthine and Vincracine (Vincristine)) by 41.85 µg/g DW, total phenolic compounds by 3948.6 µg gallic/g FW, the content of flavonoids 951.3 µg quercetin /g FW and carotenoids content 32.97 mg/g FW as compared to the control. An amount of 400 ppm ĸ-carrageenan treatment gave the best contents of FAA, Chl a, Chl b and anthocyanin. The element content of K, Ca, Cu, Zn and Se increased by treatments. Amino acids constituents and phenolics compounds contents were altered by ĸ-carrageenan.

Neoadjuvant chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer: Meta-analysis and trial sequential analysis of randomized controlled trials.

We aimed to compare resection and survival outcomes of neoadjuvant chemoradiotherapy (CRT) and immediate surgery in patients with resectable pancreatic cancer (RPC) or borderline resectable pancreatic cancer (BRPC). In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement standards, a systematic review of randomized controlled trials (RCTs) was conducted. Random effects modeling was applied to calculate pooled outcome data. Likelihood of type 1 or 2 errors in the meta-analysis model was assessed by trial sequential analysis. A total of 400 patients from four RCTs were included. When RPC and BRPC were analyzed together, neoadjuvant CRT resulted in a higher R0 resection rate (risk ratio [RR]: 1.55, p = 0.004), longer overall survival (mean difference [MD]: 3.75 years, p = 0.009) but lower overall resection rate (RR: 0.83, p = 0.008) compared with immediate surgery. When RPC and BRPC were analyzed separately, neoadjuvant CRT improved R0 resection rate (RR: 3.72, p = 0.004) and overall survival (MD: 6.64, p = 0.004) of patients with BRPC. However, it did not improve R0 resection rate (RR: 1.18, p = 0.13) or overall survival (MD: 0.94, p = 0.57) of patients with RPC. Neoadjuvant CRT might be beneficial for patients with BRPC, but not for patients with RPC. Nevertheless, the best available evidence does not include contemporary chemotherapy regimens. Patients with RPC and those with BRPC should not be combined in the same cohort in future studies.

Comparing the findings and diagnostic sensitivity of cardiovascular magnetic resonance in biopsy confirmed acute myocarditis with infarct-like vs. heart failure presentation.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is considered the reference imaging modality in providing a non-invasive diagnosis of acute myocarditis (AM), as it allows for the detection of myocardial injury associated with AM. However, the diagnostic sensitivity and pattern of CMR findings appear to differ according to clinical presentation. METHODS: This is a retrospective cross-sectional study. Consecutive adult patients presenting to a single tertiary centre in South Africa between August 2017 and January 2022 with AM confirmed on endomyocardial biopsy (EMB) were enrolled. Patients with infarct-like symptoms, defined as those presenting primarily with chest pain syndrome with associated ST-T wave changes on electrocardiogram, or heart failure (HF) symptoms, defined as clinical signs and symptoms of HF without significant chest discomfort, were compared using contrasted CMR and parametric techniques with EMB confirmation of AM as diagnostic gold standard. RESULTS: Forty-one patients were identified including 23 (56%) with infarct-like symptoms and 18 (44%) with HF symptoms. On CMR, the infarct-like group had significantly higher ejection fractions of both ventricles (LVEF 55.3 ± 15.3% vs. 34.4 ± 13.5%, p < 0.001; RVEF 57.3 ± 10.9% vs. 42.9 ± 18.2%, p = 0.008), without significant differences in end diastolic volumes (LVEDVI 82.7 ± 30.3 ml/m2 vs. 103.4 ± 35.9 ml/m2, p = 0.06; RVEDVI 73.7 ± 22.1 ml/m2 vs. 83.9 ± 29.9 ml/m2, p = 0.25). Myocardial oedema was detected more frequently on T2-weighted imaging (91.3% vs. 61.1%, p = 0.03) and in more myocardial segments [3.0 (IQR 2.0-4.0) vs. 1.0 (IQR 0-1.0), p = 0.003] in the infarct-like group. Despite the absence of a significant statistical difference in the prevalence of late gadolinium enhancement (LGE) between the two groups (95.7% vs. 72.2%, p = 0.07), the infarct-like group had LGE detectable in significantly more ventricular segments [4.5 (IQR 2.3-6.0) vs. 2.0 (IQR 0-3.3), p = 0.02] and in a different distribution. The sensitivity of the original Lake Louise Criteria (LLC) was 91.3% in infarct-like patients and 55.6% in HF patients. When the updated LLC, which included the use of parametric myocardial mapping techniques, were applied, the sensitivity improved to 95.7% and 72.2% respectively. CONCLUSION: The pattern of CMR findings and its diagnostic sensitivity appears to differ in AM patients presenting with infarct-like and HF symptoms. Although the sensitivity of the LLC improved with the addition of parametric mapping in the HF group, it remained lower than that of the infarct-like group, and suggests that EMB should be considered earlier in the course of patients with clinically suspected AM presenting with HF.

Exogenous Paclobutrazol Reinforces the Antioxidant and Antimicrobial Properties of Lavender (Lavandula officinalis L.) Oil through Modulating Its Composition of Oxygenated Terpenes.

Plant growth regulators can affect the primary and secondary metabolites of various plant species. However, the effect of paclobutrazol (PBZ) on the composition of lavender oil, especially related to the terpenoid pathway, is still unclear in literatures. In this study, the effect of PBZ as a foliar spray (0.200, 400 and 600 ppm) on the vegetative growth, phytochemical content, and both antioxidant and antimicrobial properties of lavender oil were investigated. The results indicated that all examined PBZ treatments led to a significant (p ≤ 0.05) decrease in growth parameters compared to the untreated plants. Meanwhile, the yield of essential oil was significantly decreased by the treatment of PBZ at 200 ppm compared to the control. In contrast, applied-PBZ significantly enhanced the chlorophyll content and displayed a marked change in the composition of the essential oil. This change included an obvious and significant increase in 3-carene, eucalyptol, γ-terpinene, α-pinocarvone, caryophyllene, ß-vetivenene, ß-santalol, ledol, geranyl isovalerate, farnesol, caryophyllene oxide, and phytol percentage. Generally, the highest significant values were achieved by the treatment of 400 ppm compared to the other treatments. Furthermore, this treatment showed the highest free radical scavenging activity against DPPH (1,1-diphenyl-2-picrylhydrazyl) by 13% over the control. Additionally, to determine the antimicrobial activities of the extracted oil, each treatment was examined against two strains of Gram positive bacteria (S. aureus and B. cereus), two strains of Gram negative bacteria (S. enteritidis and E. coli), and two fungal species (C. albicans and A. niger) represent the yeast modal and filamentous fungus, respectively. The findings demonstrated that all examined species were more sensitive to the oil that was extracted from lavender plants, treated with 400 ppm PBZ, compared to the other concentrations.

Prevalence of cardiotropic viruses in adults with clinically suspected myocarditis in South Africa.

OBJECTIVES: To determine the prevalence and types of viral pathogens in the myocardium of patients presenting with clinically suspected myocarditis in South Africa. METHOD: This is a prospective cross-sectional study. Consecutive adults presenting to a single tertiary centre in South Africa between August 2017 and January 2021 who fulfilled the European Society of Cardiology's diagnostic criteria for clinically suspected myocarditis and who had undergone the appropriate investigations, including cardiac MRI (CMR) and endomyocardial biopsy (EMB), were included. RESULTS: One hundred and two patients with clinically suspected myocarditis were enrolled. Acute myocarditis (AM) was confirmed by CMR or EMB in 82 (80.39%) patients. Viral genomes were detected by PCR in EMB specimens of 50 patients with AM. Parvovirus B19 (PVB19) was the most frequently detected virus, in 37 as monoinfection and 4 as coinfection. This was followed by Epstein-Barr virus (n=6), human herpesvirus 6 (n=2) and human bocavirus (n=1). PVB19 was also detected in 9 patients with no evidence of AM on CMR or EMB. CONCLUSION: Viral myocarditis is the most common form of myocarditis in South Africa. Local viral prevalence appears to be similar those of the developed world. The clinical significance and pathogenic role of PVB19 remains questioned, and its local background prevalence will have to be further investigated.

Routine use of fluoroscopic and real-time transthoracic echocardiographic guidance to ensure safety of right ventricular endomyocardial biopsy in a low-volume center.

To determine whether the routine use of real-time transthoracic echocardiographic (TTE) guidance in addition to fluoroscopy would ensure the safety of right ventricular endomyocardial biopsy (RV EMB) in a low-volume center. RV EMB is a valuable tool and plays an important role in the diagnosis and management of patients with myocardial diseases. However, it has yet to gain widespread acceptance due to its perceived low diagnostic yield and concerns regarding its invasive nature and potential complications. Although the safety of EMB when performed by experienced operators in high-volume centers is well established, the complication rate in low-volume centers is less well defined but appears to be higher. This is a retrospective single-center cross-sectional study. Consecutive adult patients who underwent RV EMB procedures at Tygerberg Hospital (Cape Town, South Africa) between August 2017 and December 2020 were included. RV EMB was successfully performed in 85 patients. No major complications were reported. Five (5.88%) patients experienced minor complications: three transient right bundle branch blocks and two hemodynamically stable ventricular tachycardia. A definitive biopsy diagnosis was made in 37 (43.54%) patients. The average procedural time was 27.06 min, which equated to 4.09 min per specimen taken. The routine use of real-time TTE guidance in addition to fluoroscopy ensured the safety of RV EMB in a low-volume center without unnecessarily prolonging procedural time.

The effect of intraoperative wound protector use on the risk of surgical site infections in patients undergoing pancreatoduodenectomy: a systematic review and meta-analysis.

AIMS: To evaluate the effect of intraoperative wound protectors on the risk of surgical site infection (SSI) in patients undergoing pancreatoduodenectomy. METHODS: In compliance with PRISMA statement standards, electronic databases were searched to identify all studies comparing wound protector use with no wound protector use in patients undergoing pancreatoduodenectomy. SSI (superficial or deep) was considered primary outcome measure. The secondary outcome measures included superficial SSI, deep SSI, and organ-space SSI. Random effects modelling was applied to calculate pooled outcome data. The certainty of evidence was assessed using GRADE system. RESULTS: A total of 12159 patients from four studies were included. The included populations in both groups were comparable in terms of baseline characteristics. The use of wound protector was associated with lower risk of superficial or deep SSI (OR: 0.55, 95% CI 0.43-0.70, P<0.00001), superficial SSI (OR: 0.59, 95% CI 0.46-0.76, P<0.0001), and organ-space SSI (OR: 0.80, 95% CI 0.72-0.90, P=0.0002). There was no difference between the two groups in terms of the risk of deep SSI (OR: 0.68, 95% CI 0.43-1.06, P=0.09) although this may be subject to type 2 error. CONCLUSIONS: The results of current study suggests that the use of intraoperative wound protector during pancreatoduodenectomy may reduce the risk of postoperative SSI. The quality of the available evidence is moderate with high certainty. While evidence from future randomised controlled trials could increase the robustness of our conclusions, we do not hesitate to recommend the use of wound protectors during pancreatoduodenectomy based on the current evidence.

Level 2a evidence comparing robotic versus laparoscopic left lateral hepatic sectionectomy: a meta-analysis.

OBJECTIVES: To evaluate comparative outcomes of robotic and laparoscopic left lateral hepatic sectionectomy (LLS). METHODS: A systematic search of PubMed, Web of Science, EMBASE and bibliographic reference lists with application of a combination of free text and controlled vocabulary search adapted to thesaurus headings, search operators and limits was conducted. Overall, minor (Clavien-Dindo grade < III) and major (Clavien-Dindo grade > III) postoperative complications, mortality, volume of blood loss, conversion to an open procedure, procedure time, length of hospital stay, cost-effectiveness and R1 resection were the evaluated outcome measures. RESULTS: Seven comparative observational studies reporting a total of 319 patients of whom 150 underwent robotic LLS and the remaining 169 patients underwent laparoscopic LLS were included. The robotic approach was associated with significantly longer procedure time (MD: 29.40 min, p = 0.01) and higher cost (MD: $4170, p < 0.00001) compared to the laparoscopic approach. There was no significant difference in overall postoperative morbidity (OR: 1.29, p = 0.62), Clavien-Dindo grade < III (OR: 1.65, p = 0.49), Clavien-Dindo grade > III (OR: 1.18, p = 0.85), perioperative mortality (RD: 0.00, p = 1.00), volume of blood loss (MD: 1.96 mls, p = 0.91), conversion to an open procedure (RD: - 0.02, p = 0.46), length of hospital stay (MD: 0.22 day, p = 0.52) or R1 resection (RD:0.00, p = 1.00) between two groups. CONCLUSIONS: Meta-analysis of the best available evidence (level 2) demonstrated that robotic LLS is associated with significantly longer procedure time and higher cost and similar perioperative outcomes compared to the laparoscopic approach. Future randomised studies are required to evaluate short-term perioperative, long-term oncological and surgeon-centred outcomes.

Development of an arterial tree in C6 gliomas but not in A375 melanomas.

The microcirculation of tumors is severely disturbed. Tumors are usually supplied by fragile capillaries and do not possess the natural hierarchy of blood vessels. The detection of specific markers for arterial and venous endothelial cells (ECs) now enables us to study the vascular tree in tumors. We have injected rat C6 glioma and human A375 melanoma cells into 3.5- to 4-day-old avian embryos. After 10-12 days of reincubation the tumor cells formed solid tumors vascularized by host ECs. In contrast to the melanomas, the gliomas induced an almost normal vascular tree with arterial and venous vessels. The arterial vessels express the arterial EC marker ephrin-B2, and possess a media of smooth muscle alpha-actin (alphaSMA)-positive cells. Venular vessels in the gliomas are ephrin-B2-negative/alphaSMA-positive. Although the gliomas may represent a rare case of vascular tree induction in tumors, the results underline the heterogeneity of tumor-induced angiogenesis. This has an impact on tumor blood flow and thereby also on the efficacy of chemotherapy and radiotherapy.