Despite their proven value in reducing morbidity and mortality in different grades of heart failure, angiotensin converting enzyme (ACE) inhibitors continue to be underused. One reason for this is clinicians' apprehension of first-dose hypotension. We conducted a double-blind, randomised, placebo-controlled parallel group study to investigate the effect of various ACE inhibitors on first-dose hypotension. Eighty unselected patients were randomised into five treatment groups: placebo, captopril 6.25 mg, enalapril 2.5 mg, perindopril 2 mg and lisinopril 2.5 mg. Blood pressure was measured at baseline, half hourly for two hours and hourly for three hours after drug treatment. The maximum drops in mean arterial pressure (in mmHg +/- SD) were placebo 5.89 +/- 2.65, perindopril 5.29 +/- 2.49, enalapril 13.28 +/- 3.31, lisinopril 15.04 +/- 5.74 and captopril 16.76 +/- 5.74 (all p < 0.05 vs placebo except for perindopril). Perindopril, unlike the other ACE inhibitors studied, did not produce first-dose hypotension following its initiation in patients with congestive heart failure.
Purple urine bag syndrome (PUBs) is a rare and startling phenomenon of purple discolouration in the urine or urinary catheter and bag. It is reported in chronically debilitated elderly patients, mostly in women on long-term urinary catheters. Its prevalence is strikingly more common in nursing home residents. Several factors contribute to the formation of indigo (blue) and indirubin (red) pigments from a breakdown of dietary tryptophan, which stains the urine purple. These factors include constipation, dysmotility of the bowel, bowel bacterial overgrowth, dehydration, and urinary tract infection. The presence of purple urine may cause undue alarm to both the patient and the doctor. Thus, we present this case report on an 86-year-old woman, a nursing home resident on a long-term urinary catheter, who presented to the primary care clinic. Her urine cleared after antibiotic therapy, replacement of her urinary catheter, and supportive management, which included hydration and nutrition. In addition to these measures, reducing the time between urinary catheter changes was recommended to prevent recurrence of this condition.
Polyalthia bullata is an endangered medicinal plant species. Hence, establishment of P. bullata callus culture is hoped to assist in mass production of secondary metabolites. Leaf and midrib were explants for callus induction. Both of them were cultured on Murashige and Skoog (MS) and Woody Plant Medium (WPM) containing different types and concentrations of auxins (2,4-dichlorophenoxyacetic acid (2,4-D), α-naphthaleneacetic acid (NAA), picloram, and dicamba). The callus produced was further multiplied on MS and WPM supplemented with different concentrations of 2,4-D, NAA, picloram, dicamba, indole-3-acetic acid (IAA), and indole-3-butyric acid (IBA) media. The quantification of total phenolic content (TPC), total flavonoid content (TFC) and antioxidant capacity was further carried out on P. bullata callus, and the results were subjected to correlation analysis. Among the media, the WPM + 16.56 µM picloram (53.33 ± 22.06%) was the best for callus induction while MS + 30 µM dicamba was the best for callus multiplication. The TPC, TFC, and EC50 of DPPH scavenging activity were determined at 0.657 ± 0.07 mg GAE/g FW, 0.491 ± 0.03 mg QE/g, and 85.59 ± 6.09 µg/mL in P. bullata callus, respectively. The positive correlation between DPPH scavenging activity with TPC was determined at r = 0.869, and that of TFC was at r = 0.904. Hence, the P. bullata callus has an ability to accumulate antioxidants. It therefore can be a medium for secondary metabolites production.
Purple urine bag syndrome (PUBs) is a rare and startling phenomenon of purple discolouration
in the urine or urinary catheter and bag. It is reported in chronically debilitated elderly patients,
mostly in women on long-term urinary catheters. Its prevalence is strikingly more common in
nursing home residents. Several factors contribute to the formation of indigo (blue) and indirubin
(red) pigments from a breakdown of dietary tryptophan, which stains the urine purple. These
factors include constipation, dysmotility of the bowel, bowel bacterial overgrowth, dehydration, and
urinary tract infection. The presence of purple urine may cause undue alarm to both the patient and
the doctor. Thus, we present this case report on an 86-year-old woman, a nursing home resident
on a long-term urinary catheter, who presented to the primary care clinic. Her urine cleared
after antibiotic therapy, replacement of her urinary catheter, and supportive management, which
included hydration and nutrition. In addition to these measures, reducing the time between urinary
catheter changes was recommended to prevent recurrence of this condition.
Two new heteroyohimbine-type oxindole alkaloids, rauniticine-allo-oxindole B and rauniticinic-allo acid B, have been successfully isolated from the stems extract of Malaysian Uncaria longiflora var. pteropoda. The structures of the two new alkaloids were determined by spectroscopic analysis.
Violacein, violet pigment produced by Chromobacterium violaceum, has attracted much attention recently due to its pharmacological properties including antibacterial activity. The present study investigated possible antibacterial mode of action of violacein from C. violaceum UTM5 against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) strains. Violet fraction was obtained by cultivating C. violaceum UTM5 in liquid pineapple waste medium, extracted, and fractionated using ethyl acetate and vacuum liquid chromatography technique. Violacein was quantified as major compound in violet fraction using HPLC analysis. Violet fraction displayed bacteriostatic activity against S. aureus ATCC 29213 and methicillin-resistant S. aureus ATCC 43300 with minimum inhibitory concentration (MIC) of 3.9 μg/mL. Fluorescence dyes for membrane damage and scanning electron microscopic analysis confirmed the inhibitory effect by disruption on membrane integrity, morphological alternations, and rupture of the cell membranes of both strains. Transmission electron microscopic analysis showed membrane damage, mesosome formation, and leakage of intracellular constituents of both bacterial strains. Mode of action of violet fraction on the cell membrane integrity of both strains was shown by release of protein, K+, and extracellular adenosine 5'-triphosphate (ATP) with 110.5 μg/mL, 2.34 μg/mL, and 87.24 ng/μL, respectively, at 48 h of incubation. Violet fraction was toxic to human embryonic kidney (HEK293) and human fetal lung fibroblast (IMR90) cell lines with LC50 value of 0.998 ± 0.058 and 0.387 ± 0.002 μg/mL, respectively. Thus, violet fraction showed a strong antibacterial property by disrupting the membrane integrity of S. aureus and MRSA strains. This is the first report on the possible mode of antibacterial action of violet fraction from C. violaceum UTM5 on S. aureus and MRSA strains.
Plant tissue or cell culture keeps a significant role in micro-propagation in the plant production industry. Combination of 6-Benzylaminopurine (BAP) and other plant growth regulators like 1-Naphthaleneacetic acid (NAA) or Indole-3-acetic acid (IAA) or indole-3-butyric acid (IBA) was used in the most of the research in tissue culture. The study was carried out to investigate the optimization of the concentration of IBA and BAP combination (0, 0.25, 0.50, 1.0, 1.50, 2.0, 2.5, 3.0 and 3.5 mg/l) for the root, callus and leaf proliferation from the leaf cutting slice. The highest number (6.75) of root proliferation was observed in the concentration of 2.0 mg/l IBA+0.25 mg/l BAP combination. The callus initiation was found in the concentration of IBA 1.0-3.5 mg/l+BAP 1.0-2.0 mg/l. However, the highest callus weight was observed at the concentration of IBA 1.5 mg/l+BAP 1.0 mg/l combination than other combination of concentrations. Positively leaf initiation and formation was better in the concentration of IBA 1-3.5 mg/l+BAP 1.0-2.0 mg/l combination. In addition, the 2,2-diphenyl-2-picrylhydarzyl (DPPH) free radical scavenging potential was higher (70.1%) in leaves extract than in callus extracts (46.3%) at the concentration of 10 mg/ml though both extracts had lower DPPH free radical scavenging activity compared to the positive control, vitamin C and BHT. Theresults conclude that the optimum concentration was IBA 1.5 mg/l+BAP 1.0 mg/l combination to produce callus cell proliferation and concentration of 2.0 mg/l IBA+0.25 mg/l BAP combination was the optimum for root proliferation of broccoli in vitro.
As a hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, Fluvastatin (FLV) is used for reducing low-density lipoprotein (LDL) cholesterol as well as to prevent cardiovascular problems. FLV showed cell line cytotoxicity and antitumor effect. Melittin (MEL) exhibits antineoplastic activity and is known to be promising as a therapeutic option for cancer patients. The aim of this work was to investigate the combination of FLV with MEL loaded hybrid formula of phospholipid (PL) with alpha lipoic acid (ALA) nanoparticles to maximize anticancer tendencies. This study examines the optimization of the prepared formulation in order to minimize nanoparticles size and maximize zeta potential to potentiate cytotoxic potentialities in colon cancer cells (Caco2), cell viability, cell cycle analysis and annexin V were tested. In addition to biological markers as P53, Bax, bcl2 and Caspase 3 evaluation The combination involving FLV PL ALA MEL showed enhanced cytotoxic potentiality (IC50 = 9.242 ± 0.35 µg/mL), about twofold lower, compared to the raw FLV (IC50 = 21.74 ± 0.82 µg/mL). According to studies analyzing cell cycle, optimized FLV PL ALA MEL was found to inhibit Caco2 colon cancer cells more significantly than other therapeutic treatments, wherein a higher number of cells were found to accumulate over G2/M and pre-G1 phases, whereas G0/G1/S phases witnessed the accumulation of a lower number of cells. The optimized formulation may pave the way for a novel and more efficacious treatment for colon cancer.
Matched MeSH terms: Indoles/pharmacology; Indoles/therapeutic use
Parkinson disease (PD) is a common, progressive neurodegenerative disorder, characterized by marked depletion of striatal dopamine and degeneration of dopaminergic neurons in the substantia nigra.
Twenty five derivatives of indole carbohydrazide (1-25) had been synthesized. These compounds were characterized using 1H NMR and EI-MS, and further evaluated for their α-amylase inhibitory potential. The analogs (1-25) showed varying degree of α-amylase inhibitory potential. ranging between 9.28 and 599.0µM when compared with standard acarbose having IC50 value 8.78±0.16µM. Six analogs, 25 (IC50=9.28±0.153µM), 22 (IC50=9.79±0.43µM), 4 (IC50=11.08±0.357µM), 1 (IC50=12.65±0.169µM), 8 (IC50=21.37±0.07µM) and 14 (IC50=43.21±0.14µM) showed potent α-amylase inhibition as compared to the standard acarbose (IC50=8.78±0.16µM). All other analogs displayed good to moderate inhibitory potential. Structure-activity relationship was established through the interaction of the active compounds with enzyme active site with the help of docking studies.
Natural products are the main source of motivation to design and synthesize new molecules for drug development. Designing new molecules against β-glucuronidase inhibitory is utmost essential. In this study indole analogs (1-35) were synthesized, characterized using various spectroscopic techniques including 1H NMR and EI-MS and evaluated for their β-glucuronidase inhibitory activity. Most compounds were identified as potent inhibitors for the enzyme with IC50 values ranging between 0.50 and 53.40μM, with reference to standard d-saccharic acid 1,4-lactone (IC50=48.4±1.25μM). Structure-activity relationship had been also established. The results obtained from docking studies for the most active compound 10 showed that hydrogen bond donor features as well as hydrogen bonding with (Oε1) of nucleophilic residue Glu540 is believed to be the most importance interaction in the inhibition activity. It was also observed that hydroxyl at fourth position of benzylidene ring acts as a hydrogen bond donor and interacts with hydroxyl (OH) on the side chain of catalysis residue Tyr508. The enzyme-ligand complexed were being stabilized through electrostatic π-anion interaction with acid-base catalyst Glu451 (3.96Å) and thus preventing Glu451 from functioning as proton donor residue.
Toluene (C7H8) a hydrocarbon in crude oil, is a common contaminant in soil and groundwater. In this study, the ability to degrade toluene was investigated from twelve bacteria isolates which were isolated from soil contaminated with oil. Out of 12 bacterial isolates tested, most of Pseudomonas sp. showed the capability to grow in 1 mM of toluene compared with other isolates on the third day of incubation. Based on enzyme assays towards toluene monooxygenase, Pseudomonas aeruginosa UKMP-14T and Bacillus cereus UKMP-6G were shown to have the highest ability to degrade toluene. The toluene monoxygenase activity was analysed by using two calorimetric methods, Horseradish peroxidase (HRP) and indole-indigo. Both of the methods measured the production of catechol by the enzymatic reaction of toluene monooxygenase. In the HRP assay, the highest enzyme activity was 0.274 U/mL, exhibited by Pseudomonas aeruginosa UKMP-14T. However, for indole-indigo assay, Bacillus cereus UKMP-6G produced the highest enzyme activity of 0.291 U/ml. Results from both experiments showed that Pseudomonas aeruginosa UKMP-14T and Bacillus cereus UKMP-6G were able to degrade toluene.
Manipulation and injection of single nanosensors with high cell viability is an emerging field in cell analysis. We propose a new method using fluorescence nanosensors with a glass nanoprobe and optical control of the zeta potential. The nanosensor is fabricated by encapsulating a fluorescence polystyrene nanobead into a lipid layer with 1,3,3-trimethylindolino-6'-nitrobenzopyrylospiran (SP), which is a photochromic material. The nanobead contains iron oxide nanoparticles and a temperature-sensitive fluorescent dye, Rhodamine B. The zeta potential of the nanosensor switches between negative and positive by photo-isomerization of SP with ultraviolet irradiation. The positively-charged nanosensor easily adheres to a negatively-charged glass nanoprobe, is transported to a target cell, and then adheres to the negatively-charged cell membrane. The nanosensor is then injected into the cytoplasm by heating with a near-infrared (NIR) laser. As a demonstration, a single 750 nm nanosensor was picked-up using a glass nanoprobe with optical control of the zeta potential. Then, the nanosensor was transported and immobilized onto a target cell membrane. Finally, it was injected into the cytoplasm using a NIR laser. The success rates of pick-up and cell immobilization of the nanosensor were 75% and 64%, respectively. Cell injection and cell survival rates were 80% and 100%, respectively.
In this study, a new apoptotic monoterpenoid indole alkaloid, subditine (1), and four known compounds were isolated from the bark of Nauclea subdita. Complete (1)H- and (13)C- NMR data of the new compound were reported. The structures of isolated compounds were elucidated with various spectroscopic methods such as 1D- and 2D- NMR, IR, UV and LCMS. All five compounds were screened for cytotoxic activities on LNCaP and PC-3 human prostate cancer cell-lines. Among the five compounds, the new alkaloid, subditine (1), demonstrated the most potent cell growth inhibition activity and selective against LNCaP with an IC50 of 12.24±0.19 µM and PC-3 with an IC50 of 13.97±0.32 µM, compared to RWPE human normal epithelial cell line (IC50 = 30.48±0.08 µM). Subditine (1) treatment induced apoptosis in LNCaP and PC-3 as evidenced by increased cell permeability, disruption of cytoskeletal structures and increased nuclear fragmentation. In addition, subditine (1) enhanced intracellular reactive oxygen species (ROS) production, as reflected by increased expression of glutathione reductase (GR) to scavenge damaging free radicals in both prostate cancer cell-lines. Excessive ROS could lead to disruption of mitochondrial membrane potential (MMP), release of cytochrome c and subsequent caspase 9, 3/7 activation. Further Western blot analyses showed subditine (1) induced down-regulation of Bcl-2 and Bcl-xl expression, whereas p53 was up-regulated in LNCaP (p53-wild-type), but not in PC-3 (p53-null). Overall, our data demonstrated that the new compound subditine (1) exerts anti-proliferative effect on LNCaP and PC-3 human prostate cancer cells through induction of apoptosis.
Asparagus officinalis as a valuable medicinal plant has a low multiplication rate using the conventional methods. This study was carried out to establish an efficient in vitro propagation protocol and also to compare some biological activities of in vivo and in vitro grown Asparagus. The nodal explants were cultured on MS medium supplemented with different concentrations of 6-benzylaminopurine (BAP) and 1-Naphthaleneacetic acid (NAA) or kinetin (Kn) and Indolebutyric acid (IBA), under light and dark conditions. After 6 weeks of culture, the highest percentage (100%) of callus formation was found in 17 of treatments under dark condition and 3 treatments under light condition. Also between the two groups of hormones, Kn +IBA showed better results in promoting callus formation. The highest average number of shoots (4.25) of size 4 mm or more per explant, formed under dark condition using 1.5 mg/L BAP mixed with 0.05 mg/L NAA. Rooting was best induced in shoots excised from shoot cultures which were proliferated on MS medium supplemented with an optimal concentration of 0.4 mg/L IBA (2 roots per explant). In the second part of the study, the extracts of in vivo and in vitro grown plants as well as callus tissue were tested for their total phenolic and flavonoid content, antioxidant and antityrosinase activities, using two different extraction solvents (methanol and hexane). The methanol extract of in vivo grown plants showed a significantly higher amount of total phenolic and flavonoid content. The antioxidant activity of tested samples followed this order; in vivo plant > callus > in vitro plant.
Blastocystis sp. is known to be the most commonly found intestinal protozoan parasite in human fecal surveys and has been incriminated to cause diarrhea and abdominal bloating. Binary fission has been widely accepted as the plausible mode of reproduction for this parasite. The present study demonstrates that subjecting the parasites in vitro to higher temperature shows the proliferation of parasite numbers in cultures. Transmission electron microscopy was used to compare the morphology of Blastocystis sp. subtype 3 isolated from a dengue patient having high fever (in vivo thermal stress) and Blastocystis sp. 3 maintained at 41 °C (in vitro thermal stress) and 37 °C (control). Fluorescence stains like acridine orange (AO) and 4',6'-diamino-2-phenylindole (DAPI) were used to demonstrate the viability and nuclear content of the parasite for both the in vitro and in vivo thermal stress groups of parasites. Blastocystis sp. at 37 °C was found to be mostly vacuolar whereas the in vitro thermal stressed isolates at 41 °C were granular with electron dense material seen to protect the granules within the central body. Parasites of the in vivo thermal stressed group showed similar ultrastructure as the in vitro ones. AO and DAPI staining provided evidence that these granules are viable which develop into progenies of Blastocystis sp. These granular forms were then observed to rupture and release progenies from the mother cells whilst the peripheral cytoplasmic walls were seen to degrade. Upon exposure to high temperature both in vitro and in vivo, Blastocystis sp. in cultures show higher number of granular forms seen to be protected by the electron dense material within the central body possibly acting as a protective mechanism. This is possibly to ensure the ability to survive for the granules to be developed as viable progenies for release into the host system.
Three-component reaction of a series of 1-acryloyl-3,5-bisbenzylidenepiperidin-4-ones with isatin and L-proline in 1:1:1 and 1:2:2 molar ratios in methanol afforded, respectively the piperidone-grafted novel mono- and bisspiro heterocyclic hybrids comprising functionalized piperidine, pyrrolizine and oxindole ring systems in good yields. The in vitro evaluation of cholinesterase enzymes inhibitory activity of these cycloadducts disclosed that monospiripyrrolizines (8a-k), are more active with IC50 ranging from 3.36 to 20.07 μM than either the dipolarophiles (5a-k) or bisspiropyrrolizines (9a-k). The compounds, 8i and 8e with IC50 values of 3.36 and 3.50 μM, respectively showed the maximum inhibition of acethylcholinesterase (AChE) and butrylylcholinestrase (BuChE). Molecular modeling simulation, disclosed the binding interactions of the most active compounds to the active site residues of their respective enzymes. The docking results were in accordance with the IC50 values obtained from in vitro cholinesterase assay.
This study was designed to investigate the effect of 3D TECA hydrogel on the inflammatory-induced senescence marker, and to assess the influence of the gel on the periodontal ligament fibroblasts (PDLFs) migration in wound healing in vitro. PDLFs were cultured with 20 ng/ml TNF-α to induce inflammation in the presence and absence of 50 µM 3D TECA gel for 14 d. The gel effect on the senescence maker secretory associated-β-galactosidase (SA-β-gal) activity was measured by a histochemical staining. Chromatin condensation and DNA synthesis of the cells were assessed by 4',6-diamidino-2-phenylindole and 5-ethynyl-2'-deoxyuridine fluorescent staining respectively. For evaluating fibroblasts migration, scratch wound healing assay and Pro-Plus Imaging software were used. The activity of senescence marker, SA-β-gal, was positive in the samples with TNF-α-induced inflammation. SA-β-gal percentage is suppressed (>65%, P
A methanol-soluble extract of the bark of Myristica cinnamomea was found to exhibit anti-quorum sensing activity, and subsequent bioassay-guided isolation led to the identification of the active compound malabaricone C (1). Compound 1 inhibited violacein production by Chromobacterium violaceum CV026 when grown in the presence of a cognate signaling molecule, N-3-oxohexanoyl-homoserine lactone. Furthermore, 1 inhibited the quorum sensing-regulated pyocyanin production and biofilm formation in Pseudomonas aeruginosa PAO1. These results suggest that the anti-quorum sensing activity of 1 and related molecules should be investigated further.
The quorum sensing (QS) system has been used by many opportunistic pathogenic bacteria to coordinate their virulence determinants in relation to cell-population density. As antibiotic-resistant bacteria are on the rise, interference with QS has been regarded as a novel way to control bacterial infections. As such, many plant-based natural products have been widely explored for their therapeutic roles. These natural products may contain anti-QS compounds that could block QS signals generation or transmission to combat QS pathogens. In this study, we report the anti-QS activities of four different Chinese herbal plant extracts: Poria cum Radix pini, Angelica dahurica, Rhizoma cibotii and Schizonepeta tenuifolia, on Pseudomonas aeruginosa PAO1. All the plants extracted using hexane, chloroform and methanol were tested and found to impair swarming motility and pyocyanin production in P.aeruginosa PAO1, particularly by Poria cum Radix pini. In addition, all the plant extracts also inhibited violacein production in C.violaceum CV026 up to 50% while bioluminescence activities were reduced in lux-based E. coli biosensors, pSB401 and pSB1075, up to about 57%. These anti-QS properties of the four medicinal plants are the first documentation that demonstrates a potential approach to attenuate pathogens’ virulence determinants.