Phytoconstituents from Vernonia glaberrima Welw. Ex O. Hoffm. leaves and their cytotoxic activities on a panel of human cancer cell lines

Vernonia glaberrima is a medicinal plant that is used in African traditional medicine for the treatment of skin cancer. The aim of this study was to investigate the anticancer activity of V. glaberrima leaves and isolate its bioactive constituents. Crude methanolic leaves extract of V. glaberrima showing significant cytotoxic activity against cancer cell lines was subjected to chromatographic separation, purification and hydrolysis to yield four compounds namely, nonacosanoic acid, lupeol, 5-methylcoumarin-4-β-glucoside and 4-hydroxy-5-methylcoumarin. Three of the isolated compounds showed significant cytotoxic activity against human malignant melanoma (A375) cell line (IC50: 59.18 ± 2.70 to 139.53 ± 10.79 μg/mL) and human caucasian colon adenocarcinoma (HT-29) cell line (IC50: 4.22 ± 0.13 to 20.0 ± 1.91 μg/mL) while only lupeol displayed significant activity against human breast adenocarcinoma (MCF7) (IC50: 34.15 ± 2.32 μg/mL) cell line. CDK2 receptor and CAIX were identified through molecular docking as potential targets for the bioactive compounds. The findings of this study have revealed the therapeutic potential of V. glaberrima against breast cancer, skin cancer and colorectal carcinoma, respectively and further support its traditional uses in the treatment of skin cancer. Keywords: Vernonia glaberrima; Anticancer activity; 5-Methylcoumarin-4-β-glucoside; Molecular docking; Carbonic anhydrase I

Antibacterial effects of flavonoids and their structure-activity relationship study : A comparative interpretation

According to the latest report released by the World Health Organization, bacterial resistance to well-known and widely available antibacterial drugs has become a significant and severe global health concern and a grim challenge to tackle in order to cure infections associated with multidrug-resistant pathogenic microorganisms efficiently. Consequently, various strategies have been orchestrated to cure the severe complications related to multidrug-resistant bacteria effectively. Some approaches involved the retardation of biofilm formation and multidrug-resistance pumps in bacteria as well as the discovery of new antimicrobial agents demonstrating different mechanisms of action. In this regard, natural products namely alkaloids, terpenoids, steroids, anthraquinone, flavonoids, saponins, tannins, etc., have been suggested to tackle the multidrug-resistant bacterial strains owing to their versatile pharmacological effects. Amongst these, flavonoids, also known as polyphenolic compounds, have been widely evaluated for their antibacterial property due to their tendency to retard the growth of a wide range of pathogenic microorganisms, including multidrug-resistant bacteria. The hydroxylation of C5, C7, C3′, and C4′; and geranylation or prenylation at C6 have been extensively studied to increase bacterial inhibition of flavonoids. On the other hand, methoxylation at C3′ and C5 has been reported to decrease flavonoids’ antibacterial action. Hence, the latest information on the antibacterial activity of flavonoids is summarized in this review, with particular attention to the structure-activity relationship of this broad class of natural compounds to discover safe and potent antibacterial agents as natural products

Antibacterial effects of flavonoids and their structure-activity relationship study: a comparative interpretation

According to the latest report released by the World Health Organization, bacterial resistance to well-known and widely available antibacterial drugs has become a significant and severe global health concern and a grim challenge to tackle in order to cure infections associated with multidrug-resistant pathogenic microorganisms efficiently. Consequently, various strategies have been orchestrated to cure the severe complications related to multidrug-resistant bacteria effectively. Some approaches involved the retardation of biofilm formation and multidrug-resistance pumps in bacteria as well as the discovery of new antimicrobial agents demonstrating different mechanisms of action. In this regard, natural products namely alkaloids, terpenoids, steroids, anthraquinone, flavonoids, saponins, tannins, etc., have been suggested to tackle the multidrug-resistant bacterial strains owing to their versatile pharmacological effects. Amongst these, flavonoids, also known as polyphenolic compounds, have been widely evaluated for their antibacterial property due to their tendency to retard the growth of a wide range of pathogenic microorganisms, including multidrugresistant bacteria. The hydroxylation of C5, C7, C30, and C40; and geranylation or prenylation at C6 have been extensively studied to increase bacterial inhibition of flavonoids. On the other hand, methoxylation at C30 and C5 has been reported to decrease flavonoids’ antibacterial action. Hence, the latest information on the antibacterial activity of flavonoids is summarized in this review, with particular attention to the structure–activity relationship of this broad class of natural compounds to discover safe and potent antibacterial agents as natural products

Flavonoids as antidiabetic and anti-inflammatory agents: a review on structural activity relationship-based studies and meta-analysis

Abstract: Flavonoids are a group of naturally occurring polyphenolic secondary metabolites which have been reported to demonstrate a wide range of pharmacological properties, most importantly, antidiabetic and anti-inflammatory effects. The relationship between hyperglycaemia and inflammation and vascular complications in diabetes is now well established. Flavonoids possessing antidiabetic properties may alleviate inflammation by reducing hyperglycaemia through different mechanisms of action. It has been suggested that the flavonoids’ biochemical properties are structure-dependent; however, they are yet to be thoroughly grasped. Hence, the main aim of this review is to understand the antidiabetic and anti-inflammatory properties of various structurally diverse flavonoids and to identify key positions responsible for the effects, their correlation, and the effect of different substitutions on both antidiabetic and anti-inflammatory properties. The general requirement of flavonoids for exerting both anti-inflammatory and antidiabetic effects is found to be the presence of a C2–C3 double bond (C-ring) and hydroxyl groups at the C3’, C4’, C5, and C7 positions of both rings A and B of a flavonoid skeleton. Furthermore, it has been demonstrated that substitution at the C3 position of a C-ring decreases the anti-inflammatory action of flavonoids while enhancing their antidiabetic activity. Correlation is discussed at length to support flavonoids possessing essential pharmacophores to demonstrate equipotent effects. The consideration of these structural features may play an important role in synthesizing better flavonoid-based drugs possessing dual antidiabetic and anti-inflammatory effects. A meta-analysis further established the role of flavonoids as antidiabetic and anti-inflammatory agents

Flavonoids as antidiabetic and anti-inflammatory agents: A review on structural activity relationship-based studies and meta-analysis

Flavonoids are a group of naturally occurring polyphenolic secondary metabolites which have been reported to demonstrate a wide range of pharmacological properties, most importantly, antidiabetic and anti-inflammatory effects. The relationship between hyperglycaemia and inflammation and vascular complications in diabetes is now well established. Flavonoids possessing antidiabetic properties may alleviate inflammation by reducing hyperglycaemia through different mechanisms of action. It has been suggested that the flavonoids’ biochemical properties are structure-dependent; however, they are yet to be thoroughly grasped. Hence, the main aim of this review is to understand the antidiabetic and anti-inflammatory properties of various structurally diverse flavonoids and to identify key positions responsible for the effects, their correlation, and the effect of different substitutions on both antidiabetic and anti-inflammatory properties. The general requirement of flavonoids for exerting both anti-inflammatory and antidiabetic effects is found to be the presence of a C2–C3 double bond (C-ring) and hydroxyl groups at the C3’, C4’, C5, and C7 positions of both rings A and B of a flavonoid skeleton. Furthermore, it has been demonstrated that substitution at the C3 position of a C-ring decreases the anti-inflammatory action of flavonoids while enhancing their antidiabetic activity. Correlation is discussed at length to support flavonoids possessing essential pharmacophores to demonstrate equipotent effects. The consideration of these structural features may play an important role in synthesizing better flavonoid-based drugs possessing dual antidiabetic and anti-inflammatory effects. A meta-analysis further established the role of flavonoids as antidiabetic and anti-inflammatory agents

MECHANICAL AND ELECTRON OPTICAL PROPERTIES OF A STABILIZED COLLAPSIBLE SOIL IN TUCSON, ARIZONA (MICROSCOPY, LIME-STABILIZATION).

This dissertation deals with collapsing soils that are prevalent in Tucson, Arizona. Upon wetting, such soils generally swell under small loads but collapse under large loads. Since the recognition of such collapsing soils in Tucson, before about two decades, more collapsing soils were encountered due to booming construction. Therefore, the main goal of this research was to study in depth the mechanism by which these soils collapse and to investigate the effect of certain mechanical and chemical treatment on that mechanism. The research included studies of undisturbed, compacted, and lime-treated samples. Both mechanical and physicochemical tests were conducted. The mechanical tests included collapse, swell, and unconfined compressive strength. The physicochemical tests involved X-ray diffraction and scanning electron microscopy. Various sites of highly collapsing soils were classified with respect to collapse according to existing criteria and the soil of one site was selected for a detailed investigation. A predictive collapse criterion was developed and used to classify the collapse susceptibility of soils in Tucson. The microstructure of the selected soil was investigated before and after collapse. A physical model was proposed to explain the mechanism of collapse. The effects of initial water content, sequence of loading and wetting, and level of loading on the engineering behavior of the selected soil were investigated. Stabilization by compaction was studied using impact and static methods at seven points on the Standard Compaction Curve. The benefits of hydrated-lime additive and the short-term reactions of lime-treated samples were also studied. The research results indicated that the microstructure of the soil is highly porous due to many interassemblage pores. Fine clay particles were found either clothing or buttressing the larger silt particles. The collapse was due mainly to weakening or failure of the clay connectors between the larger soil particles due to swelling of the expansive clay minerals, reduction of the strength of clay connectors due to wetting, dispersion of the supporting buttresses, and reduction of capillary tension. Compaction by both impact and static methods minimized the collapse but not the swell of the soil. Lime treatment completely suppressed the soil's tendency toward collapse and swell

Darbepoetin Use for the Treatment of Anemia in Hemodialysis Patients in Saudi Arabia

Erythropoietin replacing proteins have improved patient outcomes and quality of life. Darbepoetin has a 3-fold longer half-life than recombinant human erythropoietin (rHuEPO). In this study, we investigate the efficacy and safety of the conversion of stable hemodialysis patients from the current short-acting r-HuEPO (EPO alfa or beta) to the long-acting darbepoetin. In addition, we verified the appropriateness of the current ratio of conversion of the short acting to the long-acting erythropoietin in an open label prospective multi-center study. The study design included 12 weeks darbepoetin administration. The conversion ratio was 200 IU of short acting r-HuEPO to 1 microgram of darbepoetin. We adjusted the dose of darbepoetin to maintain hemoglobin levels between 110-120 g/L. There were 33 patients who satisfied the entry criteria. The study was conducted from January-June, 2005. The study patients included 18 men and 15 women, the mean age was 50.4 ± 12.3 years and the mean duration on HD was 323 ± 51.9 days. There was a significant decrease in the mean dose of darbepoetin from 37.3 ± 12.9 ug/week at week 1 of the study to 20.8 ± 16.6 ug/week by the end of week 12 (p< 0.00003) while the hemoglobin level was maintained within the previously defined range. The initial conversion ratio from short-acting erythropoietin to darbepoetin was 200 IU to 1 microgram. However, at the end of week 12, the mean dose of darbepoetin decreased to an equivalent conversion ratio to 361 IU: 1 microgram. This may reflect great savings in the cost of treatment. Our experience with darbepoetin reveals that darbepoetin is effective and safe for the treatment of anemia in hemodialysis patients and has a more convenient dosing schedule than short-acting erythropoietin. The darbepoetin dosage decreases over time and savings are expected to greater with darbepoetin more than with short-acting erythropoietin with time

Successful Pregnancies Post Renal Transplantation

To evaluate the maternal and fetal outcomes in renal transplant female recipients who became pregnant from 1989 to 2005 in our center, we retrospectively studied 20 incident pregnancies in 12 renal transplant recipients; 5 (41.7 %) of them from living related, 4 (33.3%) from deceased, and 3 (25%) from living unrelated donors. The mean age at pregnancy was 30.5 ± 4.5 years and mean interval from transplantation to pregnancy was 21 ± 5.7 months with the interval was < 1 year in one patient. The mean serum creatinine (SCr) before pregnancy vs 6 months post delivery was 110 ± 24.3, and 156 ± 190 µmol/ L, respectively, (p = 0.2). All patients were normotensive during the prenatal period except two who were hypertensive, none was markedly proteinuric, and only one acute rejection episode occurred during one pregnancy. Graft loss one year post delivery occurred in 2 patients; one with elevated prenatal SCr > 132 µmol/L, and another with short interval from transplantation to pregnancy < 1 year, while the remaining 10 patients revealed current mean SCr of 105 ± 18.2 µmol/L. Complications during pregnancy inclu-ded pre-eclampsia in (25%), UTI (25%), preterm delivery < 37 weeks (30%), however, none of the pregnancies ended by abortion. Normal vaginal delivery vs cesarean section was 70% vs 30%, respectively. Gestational age at delivery was 36.3 ± 3.9 weeks, and mean fetal birth weight was 2349 ± 574 gm. Apgar score was 9-10 in all of the 20 babies, and none revealed intrauterine growth retardation or congenital anomalies. We conclude that consecutive pregnancies demons-trate long-term maternal and fetal survival and function. The major risk factors are elevated starting serum creatinine, hypertension, and short time interval from transplantation to pregnancy

Mediastinal parathyroid adenoma

We present two cases that developed clinical, biochemical and radiological evidences of primary and secondary hyperparathyroidism. In the first case the adenoma was removed through a transcervical incision and in the second case the supernumerary adenoma was removed through sternotomy. Post operatively, patients had normal serum calcium and iPTH with complete disappearance of symptoms

Antiradical and Xanthine Oxidase Inhibitory Activity Evaluations of Averrhoa bilimbi L. Leaves and Tentative Identification of Bioactive Constituents through LC-QTOF-MS/MS and Molecular Docking Approach

The objective of the present study was to investigate the antiradical and xanthine oxidase inhibitory effects of Averrhoa bilimbi leaves. Hence, crude methanolic leaves extract and its resultant fractions, namely hexane, chloroform, and n-butanol were evaluated for 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging effect and xanthine oxidase inhibitory activity. The active constituents were tentatively identified through LC-QTOF-MS/MS and molecular docking approaches. The n-butanol fraction of A. bilimbi crude methanolic leaves extract displayed significant DPPH radical scavenging effect with IC50 (4.14 ± 0.21 μg/mL) (p < 0.05), as well as xanthine oxidase inhibitory activity with IC50 (64.84 ± 3.93 μg/mL) (p < 0.05). Afzelechin 3-O-alpha-l-rhamnopyranoside and cucumerin A were tentatively identified as possible metabolites that contribute to the antioxidant activity of the n-butanol fraction