Steroids from Diplazium esculentum: Antiplasmodial activity and molecular docking studies to investigate their binding modes.

Diplazium esculentum is an edible fern commonly consumed by the local community in Malaysia either as food or medicine. Isolation work on the ethyl acetate extract of the stem of D. esculentum resulted in the purification of two steroids, subsequently identified as stigmasterol (compound 1) and ergosterol5,8-endoperoxide (compound 2). Upon further testing, compound 2 displayed strong inhibitory activity against the Plasmodium falciparum 3D7 (chloroquine-sensitive) strain, with an IC50 of 4.27±1.15 µM, while compound 1 was inactive. In silico data revealed that compound 2 showed good binding affinity to P. falciparum-Sarco endoplasmic reticulum calcium-dependent ATPase (PfATP6); however, compound 1 did not show an antiplasmodial effect due to the lack of a peroxide moiety in the chemical structure. Our data suggested that the antiplasmodial activity of compound 2 from D. esculentum might be due to the inhibition of PfATP6, which resulted in both in vitro and in silico inhibitory properties.

Steroids from Diplazium esculentum: Antiplasmodial activity and molecular docking studies to investigate their binding modes

@#Diplazium esculentum is an edible fern commonly consumed by the local community in Malaysia either as food or medicine. Isolation work on the ethyl acetate extract of the stem of D. esculentum resulted in the purification of two steroids, subsequently identified as stigmasterol (compound 1) and ergosterol5,8-endoperoxide (compound 2). Upon further testing, compound 2 displayed strong inhibitory activity against the Plasmodium falciparum 3D7 (chloroquine-sensitive) strain, with an IC50 of 4.27±1.15 µM, while compound 1 was inactive. In silico data revealed that compound 2 showed good binding affinity to P. falciparum-Sarco endoplasmic reticulum calcium-dependent ATPase (PfATP6); however, compound 1 did not show an antiplasmodial effect due to the lack of a peroxide moiety in the chemical structure. Our data suggested that the antiplasmodial activity of compound 2 from D. esculentum might be due to the inhibition of PfATP6, which resulted in both in vitro and in silico inhibitory properties.

The economic dimension of directing treated wastewater to the production of green fodder in Saudi Arabia.

This study aimed to identify the economic dimension of directing treated wastewater to the production of green fodder. To achieve its objectives, the study relied on economic equations, the method of using multiple criteria, and a scoring technique for prioritization. The study showed that green fodder is a crop that depletes water, as it consumes about 67.27% of the water used for agricultural purposes. In determining the priority of regions intending to use treated wastewater, the ranking put Riyadh region first, followed by the eastern region, the Qassim region, Hail, Makkah Al-Mukarramah, Tabuk, Asir, Al-Jawf, Jizan, Madinah, Najran, the northern borders, and Al-Baha, in this order. The area that can be cultivated with forage crops is estimated to be about 53.05 thousand hectares, with a production of 953.75 thousand tons. The cost of treating wastewater to make it usable amounts to 2126.22 million riyals, while the value of the benefits gained from its use is 2508.95 million riyals; thus, the Saudi agricultural economy achieves a net gain estimated at about 382.73 million riyals annually. Therefore, this study recommends the use of treated wastewater in the production of green fodder.

Cardiometabolic determinants of mortality in a geriatric population: is there a "reverse metabolic syndrome"?

AIMS: Diabetes or insulin resistance, overweight, arterial hypertension, and dyslipidaemia are recognized risk factors for cardiovascular (CV) disease. However, their predictive value and hierarchy in elderly subjects remain uncertain. METHODS: We investigated the impact of cardiometabolic risk factors on mortality in a prospective cohort study of 331 elderly high-risk subjects (mean age+/-SD: 85+/-7 years). RESULTS: Two-year total mortality was predicted by age, diabetes, low BMI, low diastolic blood pressure (DBP), low total and HDL cholesterol, and previous CV events. The effect of diabetes was explained by previous CV events. In non-diabetic subjects, mortality was predicted by high insulin sensitivity, determined by HOMA-IR and QUICKI indices. In multivariate analyses, the strongest mortality predictors were low BMI, low HDL cholesterol and previous myocardial infarction. Albumin, a marker of malnutrition, was associated with blood pressure, total and HDL cholesterol, and HOMA-IR. The inflammation marker CRP was associated with low total and HDL cholesterol, and high HOMA-IR. CONCLUSION: In very old patients, low BMI, low DBP, low total and HDL cholesterol, and high insulin sensitivity predict total mortality, indicating a "reverse metabolic syndrome" that is probably attributable to malnutrition and/or chronic disorders. These inverse associations limit the relevance of conventional risk factors. Previous CV events and HDL cholesterol remain strong predictors of mortality. Future studies should determine if and when the prevention and treatment of malnutrition in the elderly should be incorporated into conventional CV prevention.

Homocysteine levels and peripheral arterial occlusive disease: a prospective cohort study and review of the literature.

AIM: The aim of this study was to determine the prevalence of hyperhomocysteinemia in a population with peripheral vascular occlusive disease in Kuwait. METHODS: From November 2000 to May 2002, total serum homocysteine levels were measured in 172 consecutive patients admitted to the vascular surgery unit because of peripheral vascular arterial disease. A fluorescence polarization immunoassay was used for measuring total serum homocysteine levels. Serum homocysteine levels over 15 mol/L were considered as high. RESULTS: The mean ankle-brachial index was 0.59+/-0.2 and 0.55+/-0.2 for right and left legs, respectively. The mean serum homocysteine level was 14.9+/-4.7 mol/L (range, 4.2-50.0). High homocysteine levels were found in 70 out of 172 patients (40.7%). The prevalence of hyperhomocysteinemia was significant in patients with hypertension (P=0.03) and ischaemic heart disease (P=0.04). Binary logistic regression model showed that male gender, diabetes mellitus and hypertension were significant independent predictors for high levels of homocystinemia in peripheral vascular occlusive disease [adjusted odds ratio (OR) 2.90; 95% confidence interval (CI); 1.18-7.12; P=0.02]; [0.35 OR; 95% CI; 0.15-0.79; P=0.01] and [2.12 OR; 95% CI; 0.98-4.59; P=0.05], respectively. Diabetes was significant but appeared to protect for peripheral vascular occlusive disease in patients with high levels of serum homocysteine. CONCLUSION: Elevated homocysteinemia was found in 40.7% of patients suffering from peripheral vascular disease. In this cohort, male gender, diabetes and hypertension were found to be risk factors along with elevated homocysteine levels.

Use of the industrial yeast Candida utilis for cadmium sorption.

The sorption ability of Candida utilis biomass for cadmium ions with accumulating competence of dried cells and cells in alginate was compared. After an optimization of process conditions (pH 5.5, biomass concentration 1 g/L and c0 50 mg/L), the cadmium sorption capacity of dried yeast biomass was perceptibly higher than that of the other tested adsorbents. Considering the sorption of the dried yeast biomass equal to 100 %, the cells in alginate reached 86 % while native cells showed only 42 %.

Removal of copper ions from dilute solutions by Streptomyces noursei mycelium. Comparison with yeast biomass.

Sorption properties of Streptomyces noursei mycelium for copper ions were compared with the accumulation competence of dried and native yeast (Candida utilis) biomass. The copper sorption capacity of S. noursei after optimization was found to be higher than that of the two other adsorbents (dried yeast biomass 82 %, native Candida cells 48 % of the sorption capacity of the S. noursei mycelium).

Association between pulse pressure, carotid intima-media thickness and carotid and/or iliofemoral plaque in hypertensive patients.

Increased common carotid artery intima-media thickness (CCA-IMT) and carotid and/or iliofemoral (C/IF) plaque are frequent in subjects treated for hypertension, but their association with pulse pressure (PP) has rarely been studied. Using ultrasound techniques, CCA-IMT and C/IF plaques were studied in 323 hypertensive subjects, who were classified into four groups according to the adequacy of blood pressure (BP) control (systolic BP (SBP) <140 mmHg and diastolic BP (DBP) <90 mmHg) and PP (high or low). After adjustment for confounding variables, an increase in CCA-IMT was the only factor significantly and independently associated with high PP, irrespective of the effectiveness of blood pressure control and of antihypertensive drug treatment. CCA-IMT correlated with age, PP, waist-to-hip ratio, tobacco consumption, and heart rate. C/IF plaques correlated with age, tobacco consumption, diabetes mellitus, and dyslipidaemia. To conclude, even with SBP<140 mmHg and DBP<90 mmHg on treatment, hypertensive subjects may have increased CCA-IMT values and C/IF plaque. Four cardiovascular risk factors seem to be involved in these alterations, namely tobacco consumption, dyslipidaemia, diabetes and increased PP. Only the latter factor does not have a standardized effective treatment.

Prevalence and progression of internal carotid artery stenosis in patients with peripheral arterial occlusive disease.

OBJECTIVE: The purpose of this study was to determine the prevalence of significant carotid stenosis, to identify risk factors increasing this prevalence, and to determine the risk of progression of stenosis, in patients with peripheral arterial occlusive disease who are neurologically asymptomatic. STUDY DESIGN: Consecutive patients who underwent evaluation in a vascular laboratory for peripheral arterial occlusive disease, who had no recent neurologic symptoms, were investigated. RESULTS: From July 1999 to December 2000, 620 patients underwent duplex scanning on one occasion, and 417 on two occasions. The average age was 72 +/- 10 years, and 61% were men. An occluded internal carotid artery was found in 4.8% of patients. The prevalence of a carotid stenosis >50% was 33% on the initial evaluation. Age of more than 70 years (P =.007), diabetes mellitus (P =.042), history of stroke (P =.011), and ankle/brachial index of less than 0.8 (P =.0006), were independently associated with carotid stenosis >50%. The odds ratio associated with each of these risk factors was similar. The prevalence of carotid stenosis >50% was 16%, 21%, 38%, 47%, and 44% for patients with no, one, two, three, and four risk factors, respectively. The highest prevalence of carotid stenosis >50% was identified in patients with ankle/brachial indices of less than 0.4 (59%). During the follow-up period, no patient had a cerebrovascular event. In 15% of carotid arteries, progression from one class of stenosis to a more severe class was observed, and 6.5% of patients progressed from a lower degree to 50% to 99% stenosis. No differences in progression of disease were identified when the variables of age, diabetes, previous stroke, and ankle/brachial index of less than 0.8 were studied or when patients with zero to two of these putative risk factors were compared with patients with three or four. CONCLUSION: Screening for carotid stenosis in asymptomatic patients with peripheral vascular disease is justifiable, but not mandatory, when two or more risk factors are present or when the ankle/brachial index is less than 0.4. Rates of progression to clinically significant stenosis are low and do not justify reevaluation every 6 months. Further research to identify the optimal interval for reevaluation is needed.

Retrojugular approach for carotid endarterectomy: a prospective cohort study.

The purpose of this study was the examination of the feasibility of the retrojugular approach for carotid endarterectomy and the investigation of its safety and effectiveness. A consecutive prospective cohort of 43 patients who underwent carotid endarterectomy with the retrojugular approach was compared with a retrospective cohort of 43 patients who underwent surgery with the standard antejugular technique. Age, sex, comorbidity, diagnostic investigations, and indications for surgery were comparable in both groups. In the retrojugular group, a carotid shunt was used in 18 patients (42%) and a patch closure in 15 patients (35%), and in the antejugular group, a carotid shunt was used in 43 patients (100%) and a patch closure in 20 patients (47%). There were no perioperative deaths, strokes, nerve injuries, or 30-day postoperative neurologic events. Wound hematomas were equally distributed in both groups (5%). Transient hoarseness was present in two patients in the antejugular group. The mean operative time was 72 +/- 15 minutes for the retrojugular technique and 100 +/- 27 for the antejugular technique (P <.0001). The hospital stay was 2 +/- 1 days in both groups. In conclusion, the retrojugular approach appears to be safe and the operative time may be shorter than with the antejugular approach.

Successful treatment of threatening limb loss ischemia of the upper limb caused by ergotamine. A case report and review of the literature.

We report a case of ischemia limited to the upper limb caused by chronic use of ergotamine. The effect of this drug was not related to hypersensitivity or to the potentiating effects of other medications. The patient was successfully treated discontinuing ergotamine and administering an alpha-blocking agent for three months. A review of the literature of the vascular complications of ergotamine is presented.

Successful treatment of recurrent celiac axis compression syndrome. A case report.

The celiac axis compression syndrome is characterized by the clinical triad, epigastric pain, weight loss and postprandial emesis. The aetiology is attributed to intermittent ischaemia of the foregut. The results of three different modalities of treatment, transluminal dilatation, surgical division of the median arcuate ligament, and bypass surgery in a patient with recurrent celiac artery compression syndrome are reviewed. A 62-year-old woman with a previous partial gastrectomy presented with postprandial abdominal pain and marked weight loss. Investigations for gastrointestinal tract pathology were all negative. Angiography revealed compression of the celiac axis and an angioplasty was unsuccessful. The patient underwent surgical division of the median arcuate ligament with complete relief of symptoms, which recurred four months later. Angiography demonstrated a restenosis of the celiac axis. An aorto-celiac artery bypass was done with complete and persistent relief of symptoms at four years follow-up. This is a rare syndrome, which requires predisposing anatomic factors. In this patient, a previous partial gastrectomy with gastrojejunostomy roux-en-y caused disconnection of the pancreatico-duodenal network. Scarring renders ineffective less invasive interventions. Bypass surgery is the treatment of choice and offers durable results.

Aortic pulse wave velocity, an independent marker of cardiovascular risk.

Aortic pulse wave velocity (PWV), a classical index of aortic stiffness, may be easily measured in humans using non invasive ultrasound methods of high reproducibility. Recent epidemiological studies have shown that, independently of confounding factors as age, blood pressure and cardiac mass, aortic PWV is a predictor of cardiovascular (CV) mortality in populations of hypertensive subjects, whether they have or not end-stage renal disease. Since aortic PWV is dominantly influenced by age, this finding may be of major importance for the evaluation of CV risk in geriatric populations.

[Structure and function of the arteries of very elderly people. The PROTEGER Study (Cardiovascular Prognosis and Therapeutic Optimization in Geriatrics)]. / Structure et fonction des artères des sujets très âgés-l'étude PROTEGER. (PRonostic cardio-vasculaire et Optimisation Thérapeutique En GERiatrie).

The purpose of PROTEGER, a multicenter prospective observational study, was to determine the contribution of hemodynamic, arterial, echocardiographic and biological parameters to the evaluation of individual cardiovascular risk in the elderly. The study included patients aged over 70 years hospitalized in geriatric units with overt cardiovascular disease. Cross sectional analysis of the first 194 subjects included in the study demonstrated a high rate of arterial alterations involving both structure and function. The principal alterations observed were: high pulse pressure despite normal mean systolic and diastolic pressures, frequent and diffuse arterial calcifications, reduced compliance and distensibility, increased thickness, diameter and incremental elastic modulus of the carotid and increased pulse wave velocity. Analysis of monitoring results in the PROTEGER study will demonstrate the role of hemodynamic measurements and arterial alterations in the prediction of cardiovascular risk in hospitalized elderly.

Traumatic rupture of the thoracic aorta: cohort study and systematic review.

PURPOSE: Through a systematic review of the literature, we identified the optimal management of traumatic ruptures of the thoracic aorta (TRTA) and reported the results of a cohort of patients treated with the clamp-and-sew technique (CAS) at a tertiary trauma center. METHODS: Studies were identified through Medline and the Cochrane library and from reference lists and papers from the authors' files. Studies with a single consistent protocol (CAS, Gott shunt [GS], left heart bypass [LHB], or partial cardiopulmonary bypass [PCPB]) that reported mortality and neurologic outcomes were included. Relevance, validity, and data extraction were performed in duplicate. A retrospective review of charts from June 1992 to August 2000 provided the database for our experience. RESULTS: Twenty studies reporting on 618 patients were found to be relevant. Interobserver agreement for relevance and validity decisions was high. Mortality rates for repair with CAS, GS, LHB, and PCPB were 15%, 8%, 17%, and 10%, respectively, and for paraplegia they were 7%, 4%, 0%, and 2%, respectively. The difference in mortality rates was not statistically significant. CAS had a higher incidence of neurologic deficits than GS (odds ratio [OR], 1.8; 95% CI, 0.4-8), LHB (OR, 6.4; 95% CI, 0.8-50), and PCPB (OR, 3.4; 95% CI, 1-10). In our cohort of 25 patients, 21 underwent surgery with CAS. The median abbreviated injury severity score was 20 (range, 4-50). The mean aortic clamp time was 30 +/- 12 minutes. Aortic repair was achieved with graft interposition in 43% of patients, and simple suture was achieved in 57% of patients. Mortality (10%) and neurologic complication (paraplegia, 11%; paraparesis, 5%) rates were not statistically different from those reported in the literature. CONCLUSION: CAS is associated with a similar mortality rate but a higher incidence of neurologic deficits than methods with distal aortic perfusion.

Ruptured mycotic aneurysm of the popliteal artery. A case report and review of the literature.

We report a case of a ruptured mycotic popliteal artery aneurysm as a consequence of septic embolization from infective endocarditis. The clinical presentation and radiological findings are presented. The popliteal, tibio-peroneal, and the antero-tibial arteries were reconstructed using an in situ bifurcated saphenous vein graft. Follow-up at 24 months disclosed a patent repair with normal ankle-brachial index.

D-amino-acid oxidase--an improved production of the enzyme by the yeast Trigonopsis variabilis in a laboratory fermentor.

The cultivation of the yeast Trigonopsis variabilis producing D-amino-acid oxidase (an enzyme participating in the transformation of cephalosporin C into 7-aminocephalosporanic acid for the production of beta-lactam antibiotics) was controlled by changes of dissolved oxygen tension and extended fermentation times. The production technology was optimized on a laboratory scale and scale-up parameters were identified.

Would measurement of C-reactive protein reduce the rate of negative exploration for acute appendicitis?

BACKGROUND: Appendicectomy for suspected acute appendicitis is a common procedure. The rate of normal appendices unnecessarily removed remains high (15-30%) despite several techniques and investigations used to improve the diagnostic accuracy. Many studies investigated the role of raised C-reactive protein in improving the diagnosis of acute appendicitis, but with conflicting results. This study emphasies the impact of a normal (rather than raised) serum C-reactive protein in reducing the rate of negative explorations. METHODS: In a double blind study, blood for the measurement of serum C-reactive protein (CRP) was collected pre-operatively from 78 patients just before going to the operating room for appendicectomy. The histopathology of the 78 appendices were grouped into positive (acute appendicitis) and negative (normal appendix). White blood count (WBC), CRP and the histopathology findings were correlated. RESULTS: In patients with histopathologically proven acute appendicitis both the WBC count and serum CRP level were significantly raised (P = 0.025 and P < 0.000,1 respectively). Serum CRP level was normal in 13 out of 15 negative explorations (normal appendix on histopathology). The specificity and sensitivity of serum CRP was 86.6% and 93.6%, respectively. CONCLUSION: A normal pre-operative serum CRP measurement in patients with suspected acute appendicitis is most likely associated with a normal appendix. Deferring surgery in this group of patients would probably reduce the rate of unnecessary appendicectomies.

Laparoscopic closure of perforated duodenal ulcer.

BACKGROUND: Medical treatment of peptic ulcer is highly successful, and the eradication of Helicobacter pylori (H. pylori) reduces ulcer recurrence. However, the incidence of perforated duodenal ulcer and its associated mortality have not been reduced by modern methods of therapy. Laparoscopic simple closure and omental plug by suturing, fibrin glue, and stapler have been successful. METHODS: Over a 1-year period (1996-97), 21 patients with perforated duodenal ulcer were operated on in our hospital by laparoscopic simple closure and omental patch. The mean age was 36.4 +/- 11.8 years (range, 18-61). Twenty patients were male (93.7%). The mean duration of pain was 9.1 +/- 11.7 hs (range, 2-48). Three patients had a previous history of duodenal ulcer (14.3%), and another three (14.3%) patients had a history of nonsteroidal antiinflammatory drug (NSAID) intake. Erect chest radiograph showed that 19 patients had air under the diaphragm (90.5%). Sixteen patients (76.2%) had frank pus in the abdomen, and five patients had a minimal peritoneal reaction (23.8%). RESULTS: The mean operative time was 71.6 +/- 24.6 mins (range, 40-120), and the mean hospital stay was 5.2 +/- 1.6 days (range, 3-9). The mean time to resume oral fluids was 3.1 +/- 0.8 days (range, 2-4). Only one patient was reoperated due to leakage identified by gastrographin swallow. CONCLUSIONS: This procedure is safe and efficient; however, further study of its long-term effectiveness and comparability to existing therapy is still needed.

Antimicrobial durability and rare ultrastructural colonization of indwelling central catheters coated with minocycline and rifampin.

OBJECTIVE: To determine the duration of antimicrobial activity and the efficacy of indwelling catheters coated with minocycline and rifampin in preventing ultrastructural colonization. DESIGN: Multicenter, prospective, randomized, clinical trial. SETTING: Five university-based medical centers. PATIENTS: Cohort 1 consisted of 40 randomized patients in whom an equal number of minocycline- and rifampin-coated and uncoated catheters were inserted and studied using scanning electron microscopy. Cohort 2 consisted of 118 patients who received coated catheters that were tested for the antimicrobial activity and levels of the antibiotics at the time of removal. INTERVENTIONS: Catheters pretreated with tridodecylmethylammonium chloride and subsequently coated with minocycline and rifampin; uncoated catheters (control). MEASUREMENTS AND MAIN RESULTS: Quantitative scanning electron microscopy was utilized to determine both the ultrastructural colonization in biofilm on coated and uncoated catheters. The zones of inhibition of coated catheters from studied patients against Staphylococcus epidermidis was used to determine the antimicrobial durability. High-performance liquid chromatography was used to determine antibiotic levels on indwelling coated catheters and in serum. Mild-to-heavy ultrastructural colonization was detected in 7 (35%) of 20 coated catheters and in 16 (80%) of 20 uncoated catheters (p = .004). Significant antimicrobial inhibitory activity against S. epidermidis was maintained for 16 days. Rifampin and minocycline continued to be detected on the surfaces of coated catheters for at least 2 wks after placement. Neither antibiotic was detected in the 60 serum samples obtained from 15 patients during catheterization. CONCLUSION: Coating catheters with minocycline and rifampin inhibits ultrastructural colonization of indwelling catheters and maintains effective antimicrobial activity for at least 2 wks.