Insecticidal activities of cinnamic acid esters isolated from Ocimum gratissimum L. and Vitellaria paradoxa Gaertn leaves against Tribolium castaneum Hebst (Coleoptera: Tenebrionidae).

BACKGROUND: Pest management using botanicals has been widely practiced in sub-Saharan Africa and other parts of the world in recent times. The natural compounds present in these botanicals are known to be responsible for the protection they offer against insect pests. Some of these compounds may act as single compounds to produce an effect or they may be synergistically effective. In the present study using a bioassay guided approach, two cinnamic acid derivatives, methyl cinnamate and sitosterol cinnamate, were isolated from the leaves of Ocimum gratissimum and Vitellaria paradoxa, respectively. RESULTS: The two cinnamic acid derivatives were found to show higher levels of insecticidal, larvicidal and larval growth inhibition activities against Tribolium castaneum. The LC50 of methyl cinnamate was determined to be 26.92 mg mL-1 (95% CL: 1.18.66-38.84 mg mL-1 ; slope ± SE: 2.84 ± 0.81) for the adult 8.31 mg mL-1 (95% CL: 2.39-28.83 mg mL-1 ; slope ± SE: 0.66 ± 0.28) for the larvae while the LC50 of sitosterol cinnamate was determined to be 6.92 mg mL-1 (95% CL: 3.97-12.06 mg mL-1 ; slope ± SE: 1.59 ± 0.12) the adult and 3.91 mg mL-1 (95% CL: 2.21-6.93 mg mL-1 ; slope ± SE: 1.52 ± 0.13) for the larvae. CONCLUSION: Generally, the susceptibility of adult T. castaneum to these cinnamic acid esters can be directly associated with the concentration as well as time of exposure to the compounds. The isolated compounds support the use of O. gratissimum and V. paradoxa as important botanicals for the management of storage pests. © 2019 Society of Chemical Industry.

Necessity for long-term follow-up of patients with head and neck paraganglioma and mutation in the succinate dehydrogenase genes: an index case report and literature review.

OBJECTIVE: To describe a patient with hereditary head and neck paraganglioma (HNPGL) and to review the literature on these rare tumors. METHODS: We review the English-language literature regarding SDH mutations, HNPGL, hereditary paraganglioma-pheochromocytoma syndrome, and the role of functional imaging in the follow-up of these tumors. We also describe the clinical findings, imaging results, and follow-up of a man who initially presented with HNPGL and subsequently developed metastatic pheochromocytoma 20 years later. RESULTS: A 66-year-old man presented with a history of hypertension, palpitations, sweating, and elevated urinary norepinephrine. Iodine-123-metaiodobenzylguanidine (123I-MIBG) scan demonstrated a left suprarenal mass and multiple avid lesions in the abdomen, chest, and posterior cranial fossa. Histologic examination confirmed a metastatic pheochromocytoma, and molecular genetic testing revealed a mutation in the SDHD gene. The patient had had surgery 20 years earlier for HNPGL. Although most HNPGLs arise sporadically, susceptibility genes have been identified in approximately one-third of cases. Optimal follow-up remains controversial. We reiterate a need for long-term follow-up of patients with a mutation in an SDH gene. 123I-MIBG, highly specific for identifying ectopic neuroendocrine tissue, may have a role in long-term follow-up. CONCLUSIONS: Although HNPGLs rarely metastasize, their malignant potential is difficult to predict. Routine surveillance for at-risk patients is recommended. Patients with a mutation in an SDH gene should therefore undergo regular surveillance.

Synthesis of osteotropic hydroxybisphosphonate derivatives of fluoroquinolone antibacterials.

1-Hydroxybisphosphonate derivatives of ciprofloxacin, gatifloxacin and moxifloxacin have been synthesized using Cu(I) catalyzed azide-alkyne 1,3-dipolar cycloaddition reaction. The 1,2,3-triazol linked hydroxybisphosphonate derivative of ciprofloxacin exhibited antibacterial activity comparable to the parent antibiotic and all fluoroquinolone-bisphosphonates displayed osteotropic properties in a bone model.

The effects of enamel matrix derivative and cyclic mechanical strain on human gingival fibroblasts in an in vitro defect healing model.

Gingival fibroblasts (GFs) play a considerable role in the maintenance of the gingival apparatus as well as in connective tissue repair. Mobility of a periodontal wound or soft tissue graft can impair connective tissue healing from the GFs. Enamel matrix derivative (EMD) is an enamel matrix protein used clinically for periodontal regeneration of intrabony defects and furcations, as well as treatment of gingival margin recessions. The goal of this project was to compare the effects of varying concentrations of EMD, with and without cyclic mechanical strain, on cellular wound fill of human GFs using an in vitro defect healing model. GFs were seeded and cultured in six-well flexible-bottomed plates. A 3-mm wound was created in the central portion of each confluent well. Three wells were treated with each EMD concentration of 0 Μg/mL (control), 30 Μg/mL, 60 Μg/mL, or 120 Μg/mL. The plates were placed in an incubator containing a strain unit to subject test plates to cyclic strain. An identical set of control plates were not flexed. Cells were examined on days 4, 8, 12, and 16. Microphotographs were taken and wound fill measurements made using image analysis software. The percent wound fill was calculated. All nonflexed plates, regardless of EMD concentration, reached > 90% defect fill at similar rates by day 16. However, in the flexed plates, EMD had a significant negative effect on defect fill. The defect fill was 55.7% for 0 Μg/mL EMD, 48.2% for 30 Μg/mL EMD, 36.7% for 60 Μg/mL EMD, and 34.1% for 120 Μg/mL EMD on day 16 for the flexed GFs. EMD, in concentrations as high as 120 Μg/mL, did not significantly affect the amount of defect fill with nonflexed GFs. However, when the GFs were flexed, the addition of EMD had a significant negative effect on defect fill in a dose-dependent manner.

Hereditary fibrinogen A alpha-chain amyloidosis: phenotypic characterization of a systemic disease and the role of liver transplantation.

Variants of fibrinogen A alpha-chain (AFib) cause the most common type of hereditary renal amyloidosis in Europe and, possibly, the United States as well. Variant fibrinogen is produced in the liver, and solitary renal allografts fail within 1 to 7 years with recurrent amyloidosis. We assessed 22 AFib patients for combined liver and kidney transplantation (LKT) and report the clinical features and outcome. Twenty-one had E526V and 1, the R554L variant. Coronary atherosclerosis was identified in 68% and systemic atheromatosis in 55%. Vascular atheroma excised at endarterectomy and endomyocardial biopsies contained purely variant fibrinogen amyloid. Half had autonomic neuropathy. Six of 9 patients who underwent LKT are alive (67%), with good allograft function and no amyloidosis at median 67 months (range, 33-155 months) of follow-up. Serial technetium-99m-labeled dimercaptosuccinic acid ((99m)Tc-DMSA) renal scintigraphy in 2 cases of preemptive LKT demonstrated preserved native kidney residual function at 5 years. Four explanted livers were used successfully for domino transplantation. Fibrinogen amyloidosis is a systemic amyloid disease with visceral, vascular, cardiac, and neurologic involvement. LKT is curative; however, cardiovascular amyloidosis may preclude this option. Our data encourage evaluation of preemptive solitary liver transplantation early in the course of amyloid nephropathy to prevent hemodialysis and kidney transplantation.

Development and intra-institutional and inter-institutional validation of a comprehensive new hepatobiliary software: Part 1--Liver and gallbladder function.

OBJECTIVE: To develop a software tool for quantification of liver and gallbladder function, and to assess the repeatability and reproducibility of measurements made with it. MATERIALS AND METHODS: The software tool developed with the JAVA programming language uses the JAVA2 Standard Edition framework. After manual selection of the regions of interest on a 99mTc hepatic iminodiacetic acid study, the program calculates differential hepatic bile flow, basal duodeno-gastric bile reflux (B-DGBR), hepatic extraction fraction (HEF) of both the lobes with deconvolutional analysis and excretion half-time with nonlinear least squares fit. Gallbladder ejection fraction, ejection period (EP), ejection rate (ER), and postcholecystokinin (CCK) DGBR are calculated after stimulation with CCK-8. To assess intra-observer repeatability and intra-observer reproducibility, measurements from 10 normal participants were analyzed twice by three nuclear medicine technologists at the primary center. To assess inter-site reproducibility, measurements from a superset of 24 normal participants were also assessed once by three observers at the primary center and single observer at three other sites. RESULTS: For the 24 control participants, mean+/-SD of hepatic bile flow into gallbladder was 63.87+/-28.7%, HEF of the right lobe 100+/-0%, left lobe 99.43+2.63%, excretion half-time of the right lobe 21.50+6.98 min, left lobe 28.3+/-11.3 min. Basal DGBR was 1.2+/-1.0%. Gallbladder ejection fraction was 80+/-11%, EP 15.0+/-3.0 min, ER 5.8+/-1.6%/min, and DGBR-CCK 1.3+/-2.3%. Left and right lobe HEF was virtually identical across readers. All measures showed high repeatability except for gallbladder bile flow, basal DGBR, and EP, which exhibited marginal repeatability. Ejection fraction exhibited high reproducibility. There was high concordance among the three primary center observers except for basal DGBR, EP, and ER. Concordance between the primary site and one of the other sites was high, one was fair, and one was poor. CONCLUSION: New United States Food and Drug Administration-approved personal computer-based Krishnamurthy Hepato-Biliary Software for quantification of the liver and gallbladder function shows promise for consistently repeatable and reproducible results both within and between institutions, and may help to promote universal standardization of data acquisition and analysis in nuclear hepatology.

Midgut neuroendocrine tumours with liver metastases: results of the UKINETS study.

We intended to identify the prognostic factors and the results of interventions on patients with liver metastatic midgut carcinoids. Five institutions that are part of United Kingdom and Ireland neuroendocrine tumour (NET) group took part in this study. Patients were included if they had histology proven NET of midgut origin and liver metastases at the time of the study. Clinical and biochemical data were collected retrospectively from hospital charts, pathology reports, radiology reports and biochemistry records for each patient. Three hundred and sixty patients were included in the study. The median survival from date of diagnosis was 7.69 years (confidence interval (CI) 6.40-8.99) and 5.95 years (CI 5.02-6.88) from date of diagnosis of liver metastases. On univariate analysis, increasing age at diagnosis, increasing urinary hydroxyindole acetic acid levels, increasing plasma chromogranin A levels, high Ki67, high tumour volume and treatment with chemotherapy were identified as factors associated with a significantly poorer outcome. Resection of liver metastases, resection of small bowel primary, treatment with somatostatin analogue therapy and treatment with peptide receptor therapy were associated with improved prognosis. Multivariate analysis revealed that age at diagnosis (P=0.014), Ki67 level (P=0.039) and resection of primary (P=0.015) were independent predictors of survival. This is the largest study to our knowledge looking specifically at the prognosis and clinical course of patients with liver metastatic midgut NETs. For the first time, we have shown that Ki67 and resection of primary are independent predictors of survival for this group of patients.

An acute osteomyelitis model in traumatized rat tibiae involving sand as a foreign body, thermal injury, and bimicrobial contamination.

The multfactorial nature of bone injuries in modern warfare and emergency trauma patients warrants enhancement of existing models. To develop a more appropriate model, rat tibiae (n = 195) were mechanically injured, divided into 2 groups (with or without thermal injury), and contaminated with a range of Staphylococcus aureus (Cowan 1) inocula. In some experiments, S. aureus inocula also contained Escherichia coli or foreign bodies (sand or soil). The primary outcome measure was the amount of S. aureus remaining in the tibia (tibial bacterial load) 24 h after contamination, reported as log10 cfu/g bone. S. aureus showed ID50 and ID95 values of 72 and 977 cfu, respectively. Values were lower than seen previously by using S. aureus strain SMH. S. aureus tibial bacterial loads were higher in tibiae with mechanical and thermal injury (log10 4.15 +/- 0.27 cfu/g) versus mechanical injury alone (log10 3.1 +/- 0.47 cfu/g, P = 0.028). The addition of E. coli to the S. aureus inoculum had no effect on tibial bacterial loads (S. aureus only, log10 4.24 +/- 0.92 cfu/g; S. aureus + E. coli, log10 4.1 +/- 1.0 cfu/g, P = 0.74). Sand, added as a foreign body, increased tibial bacterial load. Combined mechanical and thermal trauma of the tibia is associated with increased S. aureus tibial bacterial loads, increasing the risk of acute osteomyelitis. Understanding the interplay of mechanical and thermal injuries, bimicrobial contamination, and foreign bodies may improve our understanding of traumatic bone injuries and the pathogenesis of osteomyelitis.

Influence of matrix-suspended demineralized bone on osseous repair using a critical-sized defect in the rat (Rattus norvegicus) calvarium.

Demineralized freeze-dried bone (DFDB) in matrix form must be rehydrated with a carrier medium which allows for easy manipulation during periodontal surgery. The purpose of this study was to evaluate how human DFDB suspended in a polyol matrix affects new bone formation in the rat calvarium critical-sized defect (CSD) model. Fifty-five adult male Harlan Sprague-Dawley rats were assigned to 1 of 5 treatment groups: polyol, 100% DFDB, 47% DFDB/polyol, 47% DFDB, or an unfilled control. They were then placed into 8-m calvarial CSDs. The bone donor source company for the DFDB and DFDB/polyol groups was the same. Calvaria were harvested 10 weeks after surgery and evaluated histomorphometrically. The diameter of bone particles from the 3 groups containing DFDB was measured by scanning electron microscopy. There was no statistically significant difference in the percentage of bone fill between any of the groups, although the 100% DFDB group exhibited the most bone fill. The 47% DFDB/polyol and 47% DFDB groups had similar amounts of bone formation. The average size of the demineralized bone particles from the 100% DFDB group was significantly smaller than that of the other 2 groups containing DFDB. Adding a polyol to DFDB produced similar osseous regeneration in the rat calvarium defect model vs DFDB alone. Yet from a clinical standpoint, the polyol enhanced graft handling and stability. Graft particle size may have an effect on bone fill.

Hepatobiliary scintigraphy after Kasai procedure for biliary atresia: clinical correlation and prognostic value.

BACKGROUND/PURPOSE: Kasai portoenterostomy (KP) is regarded as first-line treatment for biliary atresia, although its postoperative course is often unpredictable. Hepatobiliary scintigraphy using technetium-labeled iminodiacetic acid derivatives offers a dynamic, objective assessment both of parenchymal liver function and restored biliary excretion. The value of postoperative radionuclide scans was assessed prospectively in a large population of post-KP infants. METHODS: Radionuclide scans consisted of an intravenous dose of 20 MBq of 99mTc mebrofenin iminodiacetic acid and subsequent gamma camera imaging. Four scan variables were evaluated: the hepatic extraction fraction (HEF; ie, initial liver uptake divided by the peak vascular uptake), the half-life of tracer excretion (TEX), the shape of the excretion curve, and the presence of activity in the Roux loop at 4 hours postinjection. All infants had type 3 biliary atresia with a median age at KP of 59 days (24-120 days). To assess predictive value, outcome (clearance of jaundice and need for transplant) was assessed at 6 months (for 1-week scan) and 2 years (for 6-month scan). RESULTS: Eighty-seven infants underwent a radionuclide scan at 1 week post-KP. The median HEF was 34% (10%-90%). No relationship could be identified between HEF (P = .2) or excretion curve shape (P = .9) and outcome (at 6 months), and there were too few examples of a measurable TEX to allow meaningful comparison. The only predictive element at this time point was Roux loop activity (positive predictive value, 79%; negative predictive value, 53%; for "good" isotope bowel activity). Forty-four infants completed a second scan at 6 months. Median HEF increased from a baseline of 37% (11%-90%) to 64% (8%-100%) (P < .0001), although there was no significant intercorrelation (P = .12). The most predictive variables (of outcome at 2 years) were curve shape (positive predictive value, = 95%, negative predictive value, 82%) and TEX, and the least predictive was now Roux loop activity. CONCLUSIONS: Early (at 7 days) hepatic scintigraphy is not predictive of poor outcome in general, although Roux loop activity does indicate later success. Later hepatic scintigraphy (at 6 months) allows a detailed assessment of dynamic liver function with biliary excretion variables predictive of outcome in the medium term.

Worthing physiological scoring system: derivation and validation of a physiological early-warning system for medical admissions. An observational, population-based single-centre study.

BACKGROUND: Several physiological scoring systems (PSS) have been proposed for identifying those at risk of deterioration. However, the chosen specific physiological values chosen and the scores allocated have not been prospectively validated. In this study, we investigate the relative contributions of the ventilatory frequency, heart rate, arterial pressure, temperature, oxygen saturation, and conscious level to mortality in order to devise a robust scoring system. All data were collected on admission to the emergency unit. Precise 'intervention-calling scores' could then be derived to trigger interventions. METHODS: Our observational, population-based single-centred study took place in a 602-bedded district general hospital. Patients admitted to the emergency care unit at Worthing general hospital during an initial study period between July and November 2003 (n = 3184) and a further validation period between October and November 2005 (n = 1102) were included. RESULTS: Multivariate logistic regression analysis demonstrated that a ventilatory frequency > or = 20 min(-1), heart rate > or =102 min(-1), systolic blood pressure < or = 99 mm Hg, temperature <35.3 degrees C, oxygen saturation < or = 96%, and disturbed consciousness were associated with an increase in mortality. The Worthing PSS was developed from the regression coefficients associated with each variable. The model showed good discrimination with an area under the receiver operating characteristic curve, 0.74, excluding age as a variable. The discrimination of this system was significantly better than the early-warning scoring system. CONCLUSIONS: A simple validated scoring system to predict mortality in medical patients with precise 'intervention-calling scores' has been developed.

Effect of a hydroxyapatite tricalcium phosphate alloplast on osseous repair in the rat calvarium.

BACKGROUND: Bony defects caused by periodontitis are often treated by regenerative therapy using autografts and/or allografts. Alloplasts, such as hydroxyapatite or ceramics, are also used as osteoconductive materials that serve as a scaffold for new bony ingrowth. The purpose of this study was to determine the effect of hydroxyapatite tricalcium phosphate (HA-TCP) on osseous repair in the rat calvarium. METHODS: Forty-four adult male Harlan Sprague-Dawley rats were assigned to one of four treatment groups: HA-TCP macroporous disk, HA-TCP microporous disk, HA-TCP granules, and demineralized freeze-dried bone (DFDB). The materials were placed into 8-mm calvarial critical-size defects (CSD). Calvariae were harvested at 10 weeks post-surgery and evaluated histomorphometrically. RESULTS: The DFDB group had significantly (P <0.05) more new bone formation (47%) than any other group. The HA-TCP macroporous disk group had significantly (P <0.05) more new bone formation (19.7%) than the HA-TCP microporous disk (8.5%) or HA-TCP granule (6.9%) groups. CONCLUSIONS: The HA-TCP macroporous disk may elicit significant new bone formation due to its rigid space-maintaining scaffold and pore size for vascular ingrowth. It is well tolerated by host tissues and may be a suitable carrier for growth factors.

An in vitro evaluation of the antibacterial efficacy of chlorine dioxide on E. faecalis in bovine incisors.

This study investigated the ability of chlorine dioxide to eliminate Enterococcus faecalis from dentinal tubules of bovine incisors. Thirty-seven extracted bovine incisor roots were sectioned into seventy-four 5 mm disks. Standardized lumens were filled with either sterile Brain Heart Infusion Broth (contamination controls, n = 10) or BHI containing E. faecalis (1.0 x 10 cfu/ml). Disks were incubated in 5% CO2 at 37 degrees C for 72 h. To simulate endodontic instrumentation the lumens were again enlarged. Sixty disks were randomly divided into four experimental groups and filled with one of the following irrigants: 10% Clidox-S (chlorine dioxide), 13.8% BioClenz (chlorine dioxide), 5.25% Clorox, or saline. The disks were incubated for 30 min and were then frozen, pulverized, serially diluted in phosphate buffered saline, and plated on BHI plates in triplicate. Total colony forming units were counted macroscopically. Statistical analysis of the data was performed with a Kruskal-Wallis one-way ANOVA on ranks (p < 0.05, n = 60). Bacterial counts, expressed in log10 cfu/disk were as follows (">" denotes significant differences): Saline > Clidox-S = BioClenz > Clorox. All negative controls were sterile. Chlorine dioxide and NaOCL were both effective in eliminating E. faecalis from the dentinal disks within 30 min.

A Monte Carlo analysis technique applied to cerebral perfusion SPECT scans.

OBJECTIVE: Voxel-based techniques are used to provide objective analyses of SPECT scans. The aim of this study was to develop a voxel-based analysis technique that uses a Monte Carlo method of statistical inference and assess this analysis technique for application to cerebral perfusion SPECT scans. METHODS: Assessment of the validity of this non-parametric, Monte Carlo method of statistical inference has been performed for a range of study designs, image characteristics and analysis parameters using phantom SPECT and Gaussian images. The Monte Carlo method of statistical inference and the voxel-based analysis technique were clinically evaluated for the analysis of individual cerebral perfusion SPECT scans using control subject data. In addition, a comparison has been performed with an existing analysis package that uses a theoretical parametric method of statistical inference (statistical parametric mapping). RESULTS: The Monte Carlo method was found to provide accurate statistical inference for phantom SPECT and Gaussian images independent of degrees of freedom, acquired counts, image smoothness and voxel significance level threshold. The clinical evaluation of the analysis of individual cerebral perfusion SPECT scans demonstrated satisfactory statistical inference and characterization of perfusion deficits. CONCLUSION: An analysis method incorporating a Monte Carlo method of statistical inference has been successfully applied for the analysis of cerebral perfusion SPECT scans.

Low-dose infectivity of Staphylococcus aureus (SMH strain) in traumatized rat tibiae provides a model for studying early events in contaminated bone injuries.

Animal models of post-traumatic acute osteomyelitis (OM) that closely mimic human scenarios, including infection prophylactic procedures such as debridement and lavage, may provide a better understanding of OM. We contaminated mechanically traumatized rat tibiae (n = 69) with various doses of a Staphylococcus aureus strain (SMH) known to cause human OM and then performed curettage and lavage. Tibiae were harvested 24 h after lavage for assessment of bacterial load and determination of minimal infective doses for 50% (ID50) and 95% (ID95) of rats. Some experiments varied tibial harvest time after lavage (n = 10); for progressive infection, tibiae were evaluated at 7 and 15 days after contamination (n = 17 for each time point). At 24 h after contamination, the ID50 was 1.8 x 10(3) CFU, and the ID95 was 9.2 x 10(3) CFU. Tibial bacterial loads did not increase with inocula greater than the ID95. Lavage removed many bacteria from bone, but it did not prevent subsequent infection or disease. At 15 days after contamination, most tibiae (14 of 17) were infected, with macroscopic and radiological signs of established OM. This newly described rat OM model, with a low ID95 despite prophylactic curettage and lavage, closely mimics events in contaminated human bone injuries. This situation will allow study of early factors in contaminated bone injuries, including clinical interventions that may reduce infection and prevent disease.

Cystatin C, an easy and reliable marker for assessment of renal dysfunction in children with liver disease and after liver transplantation.

Renal dysfunction of variable severity is being increasingly recognized as a major complication of calcineurin inhibitors (CI), in some patients even necessitating renal transplantation. Close and effective monitoring of the renal function is indicated. Current methods for this monitoring are calculation of the glomerular filtration rate (GFR) based on creatinine or exogenous substances like 51Cr-EDTA. The first method is unreliable in children and the second is expensive and cumbersome. Cystatin C has been shown to be an accurate marker of glomerular filtration but has not been evaluated in a large cohort of pediatric patients before and after liver transplantation (LT). We evaluated the accuracy of cystatin C in 62 children (30 male) with LT, who had their 51Cr-EDTA measured on 40 occasions prior to LT and on 47 occasions after LT. The reciprocal of cystatin C correlated better with 51Cr-EDTA GFR (r = .78) than the reciprocal of creatinine (r = .40). Diagnostic accuracy in the identification of reduced GFR was assessed by ROC analysis. Cystatin C yielded the highest area under the ROC curve (AUC) in all groups assessed. From these data a cutoff level of cystatin C predicting 51Cr-EDTA GFR < 80 ml/min/1.73 m2 was calculated. A level of 1.06 mg/L was found to have a sensitivity of 91% and a specificity of 81%. Applying this cutoff level in our patient group would have avoided 51Cr-EDTA GFR estimation in 43 of the 87 estimations. In conclusion, the use of this simple test could be recommended as screening of renal dysfunction in children with liver disease and after LT.