Reference intervals for CTX and P1NP in a multi-ethnic Malaysian cohort.

BACKGROUND: Well defined reference intervals are central to the utility of serum C-terminal telopeptide of type 1 collagen (CTX) and N-terminal propeptide of type I procollagen (P1NP), designated as reference markers in osteoporosis, and useful for monitoring therapeutic response in that condition. This study reports the reference intervals for plasma CTX and serum P1NP in a multi-ethnic Malaysian population. METHODS: Ethnic Malay, Chinese or Indian subjects aged 45-90 years old were recruited from Selangor, Malaysia from June 2016 to August 2018. Subjects with known medical conditions (e.g., bone disorders, malnutrition, immobilisation, renal impairment, hormonal disorders) and medications (including regular calcium or vitamin D supplements) that may affect CTX and P1NP were excluded. Additionally, subjects with osteoporosis or fracture on imaging studies were excluded. The blood samples were collected between 8 a.m. and 9 a.m. in fasting state. The CTX and P1NP were measured on Roche e411 platform in batches. RESULTS: The 2.5th-97.5th percentiles reference intervals (and bootstrapped 90%CI) for plasma CTX in men (n = 91) were 132 (94-175) - 775 (667-990) ng/L; in post-menopausal women (n = 132) 152 (134-177) - 1025 (834-1293) ng/L. The serum P1NP reference intervals in men were 23.7 (19.1-26.4) - 83.9 (74.0-105.0) µg/L, and in post-menopausal women, 25.9 (19.5-29.3) - 142.1 (104.7-229.7) µg/L. CONCLUSION: The reference intervals for plasma CTX and serum PINP for older Malaysian men and post-menopausal women are somewhat different to other published studies from the region, emphasising the importance of establishing specific reference intervals for each population.

Peroperative extent of peritoneal metastases affects the surgical outcome and survival in advanced ovarian cancer.

OBJECTIVE: Determining whether cytoreductive surgery (CRS) is feasible in patients with advanced ovarian cancer and whether extensive surgery is justified is challenging. Accurate patient selection for CRS based on pre- and peroperative parameters will be valuable. The aim of this study is to assess the association between the extent of peritoneal metastases as determined during surgery and completeness of interval CRS and survival. METHODS: This single-center observational cohort study included consecutive patients with newly diagnosed stage III-IV epithelial ovarian cancer who received neoadjuvant chemotherapy and underwent interval CRS. The 7 Region Count (7RC) was recorded during surgical exploration to systematically quantify the extent of peritoneal metastases. Logistic regression analysis was performed to predict surgical outcomes, and Cox regression analysis was done for survival outcomes. RESULTS: A total of 316 patients were included for analyses. The median 7RC was 4 (interquartile range: 2-6). Complete CRS was performed in 58%, optimal CRS in 30%, and incomplete CRS in 12% of patients. A higher 7RC was independently associated with lower odds of complete or optimal CRS in multivariable analysis (odds ratio [OR] = 0.45, 95% confidence interval [CI]: 0.33-0.63, p < 0.001). Similarly, a higher 7RC was independently associated with worse progression-free survival (hazard ratio [HR] = 1.17, 95% CI 1.08-1.26, p < 0.001) and overall survival (HR = 1.14, 95% CI 1.04-1.25, p = 0.007). CONCLUSION: The extent of peritoneal metastases, as expressed by the 7RC during surgery, is an independent predictor for completeness of CRS and has independent prognostic value for progression-free survival and overall survival in addition to completeness of CRS.

Diagnostic performance of MRI for staging peritoneal metastases in patients with colorectal cancer after neoadjuvant chemotherapy.

INTRODUCTION: MRI improves the selection of patients with colorectal cancer (CRC) and peritoneal metastases (PM) for cytoreductive surgery by accurately assessing the extent of PM reflected as the peritoneal cancer index (PCI). The performance of MRI after neoadjuvant chemotherapy (NACT) for staging PM, however is unknown. The purpose of this study was to determine whether MRI could also accurately determine the PCI after NACT. MATERIALS AND METHODS: This was a single-centre, retrospective study of patients with PM from CRC or appendiceal origin who received NACT followed by diffusion-weighted (DW)-MRI and surgery from January 2016 to February 2021. Two radiologists assessed the PCI on restaging DW-MRI (mriPCI). The reference standard was the surgical PCI (sPCI). The main outcome was the diagnostic performance of restaging DW-MRI in predicting whether patients were eligible for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), defined as a PCI < 21 with metastases on resectable locations. If CRS-HIPEC was performed, the resected peritoneal lesions were assessed and correlated with the final pathological PCI (pPCI). RESULTS: Thirty-three patients were included. Both readers correctly detected all 23 patients with resectable disease. Eight out of ten patients with unresectable disease during staging surgery were detected by both readers with MRI. The intraclass correlation (ICC) between both readers was excellent (0⋅87 (95% CI: 0⋅75 to 0⋅93)). The ICC between pPCI and mriPCI was 0⋅74 (0⋅49-0⋅88) and 0⋅82 (0⋅66-0⋅91) for the 2 readers. Surgical PCI (sPCI) had a similar correlation as mriPCI with pPCI 0⋅82 (0⋅62- 0⋅92)) and 0⋅81 (0⋅57-0⋅92)). CONCLUSION: DW-MRI is a promising tool to reassess the peritoneal cancer index after neoadjuvant chemotherapy.

Diffusion-weighted MRI assessment of the peritoneal cancer index before cytoreductive surgery.

BACKGROUND: Patients with limited peritoneal metastases from colorectal cancer may be candidates for an aggressive surgical approach including cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Selection is based on surgical inspection during laparoscopy or laparotomy. The aim of this study was to investigate whether diffusion-weighted MRI (DW-MRI) can be used to select patients for CRS-HIPEC. METHODS: This was a prospective study at a tertiary referral centre. Patients with confirmed or suspected colorectal peritoneal metastases scheduled for exploratory laparotomy or laparoscopy were eligible. Two radiologists assessed the peritoneal cancer index (PCI) on CT (CT-PCI) and DW-MRI (MRI-PCI). The reference standard was PCI at surgery. Radiologists were blinded to the surgical PCI and to each other's findings. The main outcome was the accuracy of DW-MRI in predicting whether patients had resectable disease (PCI less than 21) or not. RESULTS: Fifty-six patients were included in the study, of whom 49 could be evaluated. The mean(s.d.) PCI at surgery was 11·27(7·53). The mean MRI-PCI was 10·18(7·07) for reader 1 and 8·59(7·08) for reader 2. Readers 1 and 2 correctly staged 47 of 49 and 44 of 49 patients respectively (accuracy 96 and 90 per cent). Both readers detected all patients with resectable disease with a PCI below 21 at surgery (sensitivity 100 per cent). No patient was overstaged. The intraclass correlation (ICC) between readers was excellent (ICC 0·91, 95 per cent c.i. 0·77 to 0·96). MRI-PCI had a stronger correlation with surgical PCI (ICC 0·83-0·88) than did CT-PCI (ICC 0·39-0·44). CONCLUSION: DW-MRI is a promising non-invasive tool to guide treatment selection in patients with peritoneal metastases from colorectal cancer.

EURECCA consensus conference highlights about colon & rectal cancer multidisciplinary management: the radiology experts review.

Some interesting shifts have taken place in the diagnostic approach for detection of colorectal lesions over the past decade. This article accompanies the recent EURECCA consensus group reccomendations for optimal management of colon and rectal cancers. In summary, imaging has a crucial role to play in the diagnosis, staging assessment and follow up of patients with colon and rectal cancer. Recent advances include the use of CT colonography instead of Barium Enema in the diagnosis of colonoic cancer and as an alternative to colonoscopy. Modern mutlidetector CT scanning techniques have also shown improvements in prognostic stratification of patients with colonic cancer and clinical trials are underway testing the selective use of neoadjuvant therapy for imaging identified high risk colon cancers. In rectal cancer, high resolution MRI with a voxel size less or equal to 3 × 1 × 1 mm3 on T2-weighted images has a proven ability to accurately stage patients with rectal cancer. Moreover, preoperative identification of prognostic features allows stratification of patients into different prognostic groups based on assessment of depth of extramural spread, relationship of the tumour edge to the mesorectal fascia (MRF) and extramural venous invasion (EMVI). These poor prognostic features predict an increased risk of local recurrence and/or metastatic disease and should form the basis for preoperative local staging and multidisciplinary preoperative discussion of patient treatment options.

Mechanism of earthquake simulation as a prenatal stressor retarding rat offspring development and chinese medicine correcting the retardation: hormones and gene-expression alteration.

We aimed to investigate the mechanism of shaking as a prenatal stressor impacting the development of the offspring and Chinese medicines correcting the alterations. Pregnant rats were randomized into earthquake simulation group (ESG), herbal group (HG) which received herbal supplements in feed after shaking, and control group (CG). Findings revealed body weight and open field test (OFT) score of ESG offspring were statistically inferior to the CG and HG offspring. The corticosterone levels of ESG were higher than those of CG but not than HG. The dopamine level of ESG was slightly lower than that of the CG and of HG was higher than that of ESG. The 5-HT of ESG was higher than CG and HG. The growth hormone level of the ESG was significantly lower than ESG but not than CG. Gene expression profile showed 81 genes upregulated and 39 genes downregulated in ESG versus CG, and 60 genes upregulated and 28 genes downregulated in ESG versus HG. Eighty-four genes were found differentially expressed in ESG versus CG comparison and were normalized in ESG versus HG. We conclude that maternal shaking negatively affected physical and nervous system development, with specific alterations in neurohormones and gene expression. Chinese herbal medicine reduced these negative outcomes.

Magnolol, a major bioactive constituent of the bark of Magnolia officinalis, exerts antiepileptic effects via the GABA/benzodiazepine receptor complex in mice.

BACKGROUND AND PURPOSE: The aim of this study was to evaluate the anti-convulsant effects of magnolol (6, 6', 7, 12-tetramethoxy-2, 2'-dimethyl-1-ß-berbaman, C18H18O2) and the mechanisms involved. EXPERIMENTAL APPROACH: Mice were treated with magnolol (20, 40 and 80 mg·kg(-1)) 30 min before injection with pentylenetetrazol (PTZ, 60 mg·kg(-1), i.p.). The anti-seizure effects of magnolol were analysed using seizure models of behaviour, EEG and in vitro electrophysiology and c-Fos expression in the hippocampus and cortex. KEY RESULTS: Magnolol at doses of 40 and 80 mg·kg(-1) significantly delayed the onset of myoclonic jerks and generalized clonic seizures, and decreased the seizure stage and mortality compared with those of the vehicle-treated animals. EEG recordings showed that magnolol (40 and 80 mg·kg(-1)) prolonged the latency of seizure onset and decreased the number of seizure spikes. The anti-epileptic effect of magnolol was reversed by the GABA(A)/benzodiazepine receptor antagonist flumazenil. Pretreatment with flumazenil decreased the effects of magnolol on prolongation of seizure latency and decline of seizure stage. In a Mg(2+)-free model of epileptiform activity, using multi-electrode array recordings in mouse hippocampal slices, magnolol decreased spontaneous epileptiform discharges. Magnolol also significantly decreased seizure-induced Fos immunoreactivity in the piriform cortex, dentate gyrus and hippocampal area CA1. These effects were attenuated by pretreatment with flumazenil. CONCLUSIONS AND IMPLICATIONS: These findings indicate that the inhibitory effects of magnolol on epileptiform activity were mediated by the GABA(A) /benzodiazepine receptor complex.

Altered monocyte CD44 expression in peripheral arterial disease is corrected by fish oil supplementation.

BACKGROUND AND AIMS: CD44 and its splice variants can be expressed on all leukocytes, conferring adhesive properties and enhancing cellular recruitment to the endothelium during inflammation. CD44 expression is increased in inflammatory conditions such as rheumatoid arthritis and CD44 variant 3 (CD44v3) expression may be associated with inflammation. We have examined CD44 and CD44v3 expression on peripheral blood monocytes from patients with peripheral arterial disease (PAD) and healthy controls. We have also examined the effect of fish oil supplementation on these markers. METHODS AND RESULTS: CD44 and CD44v3 were assessed at baseline and following dietary supplementation with fish oil for 12 weeks in both PAD and control groups. Monocytes from PAD patients had higher CD44 expression than those from controls (median intensity fluorescence (MIF): 480+/-278 vs 336+/-251 (mean+/-SD); p<0.001). Following 12 weeks' dietary supplementation with fish oil, CD44 expression was reduced in PAD patients (MIF: 480+/-278 vs 427+/-262; p=0.05) but not in controls (336+/-251 vs 355+/-280; ns). Monocyte CD44v3 expression was lower in cultured monocytes from PAD patients compared to those from controls (0.15+/-0.15 vs 0.22+/-0.14 OD units; p<0.02). This was increased in the PAD group following fish oil supplementation (0.15+/-0.14 to 0.27+/-0.23 OD units; p<0.001). CONCLUSION: Monocyte CD44 and CD44v3 expression are altered in arterial disease but are returned towards levels seen in control subjects by dietary fish oil supplementation.

The effect of the major components of Salvia Miltiorrhiza Bunge on bone marrow cells.

Salvia Miltiorrhiza Bunge (SMB), a traditional Chinese medicinal herb, has been alleged to support bone healing. However, the effects of the isolated major components of SMB on osseous cells and their corresponding effective doses are still unclear. In the present study, the effects of three components of SMB, including tanshinone IIA (Ts), salvianolic acid B (salB) and protocatechuic aldehyde (Pca), on mesenchymal bone marrow cells with the potential for osteoblastic differentiation were investigated. Various concentrations of Ts, salB and Pca were added to a rat bone marrow cell culture. The total metabolic activity and differentiation of bone marrow cells were evaluated by a metabolic assay and alkaline phosphatase (ALP) activity, respectively. The morphology and number of cells was observed by phase contrast microscopy and fluorescent microscopy after propidium iodide staining, respectively. Ts suppressed the growth and differentiation of bone precursor cells. SalB exhibited a biphasic effect: the high concentration of 160 microg/mL significantly depressed the population of bone marrow cells, however, lower concentrations (3-80 microg/mL) enhanced the total metabolic activity and their ALP expression. Pca suppressed the bone marrow cell population in a dose-dependent manner. Therefore, SalB has the potential to ameliorate bone healing by stimulating both the total metabolic activity and ALP activity of osteoblastic cells. Aqueous extracts, which preferably contain salB over Pca and are free of Ts therefore are recommended for bone formation.

Cytotoxic benzo[j]fluoranthene metabolites from Hypoxylon truncatum IFB-18, an endophyte of Artemisia annua.

Two new benzo[j]fluoranthene-based secondary metabolites named daldinone C (1) and daldinone D (2), along with two known metabolites, altechromone A and (4S)-5,8-dihydroxy-4-methoxy-alpha-tetralone, were isolated from the CHCl3/MeOH (1:1) extract of a solid culture of the endophyte Hypoxylon truncatum IFB-18 harbored inside the symptomless stem tissue of Artemisia annua. The structures of the new compounds were elucidated by MS and 1D and 2D NMR spectra and by X-ray diffraction analysis. Their absolute configurations were determined unambiguously by a combination of their CD data and the established exciton chirality rule. Compounds 1 and 2 were substantially cytotoxic against SW1116 cells, with IC50 values of 49.5 and 41.0 microM, respectively, comparable to that (37.0 microM) of 5-fluorouracil. The biosynthetic pathway for 1 and 2 was postulated with the natural occurrence of benzo[j]fluoranthene analogues discussed in brief.

Repellent and insecticidal activities of essential oils from Artemisia princeps and Cinnamomum camphora and their effect on seed germination of wheat and broad bean.

Repellent and insecticidal activities of essential oils extracted from leaves of Artemisia princeps Pamp and seeds of Cinnamomum camphora (L.) Presl. against storage pests Sitophillus oryzae L. and Bruchus rugimanus Bohem were investigated. Results showed that the two individual oils displayed good, but their mixture (1:1) exhibited much better repellent activities at concentrations from 250 to 1000 microg g(-1) and insecticidal actions at concentrations 1000 microg g(-1) against the test beetles S. oryzae and B. rugimanus. Oils from A. princeps and C. camphora applied individually were significantly toxic to seed germination of wheat at 500 microg ml(-1). However, no toxic effects were found when the two oils were mixed (1:1 w/w) at the same concentration. These observations indicated that the mixture of the two plant-derived oils had a synergic effect and could be used in the control of storage pests.

Laccase production by Monotospora sp., an endophytic fungus in Cynodon dactylon.

The effects of the carbon and nitrogen sources, initial pH and incubation temperature on laccase production by the endophytic fungus Monotospora sp. were evaluated. The optimal temperature and initial pH for laccase production by Monotospora sp. in submerged culture were found to be 30 degrees C and 8.5, respectively. Maltose (2 g l(-1)) and ammonium tartrate (10 g l(-1)) were the most suitable carbon and nitrogen source for laccase production. Under optimal culture medium, the maximum laccase activity was determined to be 13.55 U ml(-1), which was approximately four times higher than that in basal medium. This is the first report on laccase production by an endophytic fungus.

New and cytotoxic anthraquinones from Pleospora sp. IFB-E006, an endophytic fungus in Imperata cylindrical.

In addition to 7-methoxy-2-methyl-3,4,5-trihydroxyanthraquinone (1), physcion (2), macrosporin (3), deoxybostrycin (4), altersolanol B (5) and dactylariol (6), a new hexahydroanthraquinone named pleospdione (7) was isolated from the culture of Pleospora sp . IFB-E006, an endophytic fungus residing in the normal stem of Imperata cylindrical (Gramineae). Structure determination of pleospdione was accomplished using IR, HR-ESI-MS, 1D and 2D NMR spectral analysis. Compounds 4 - 6 exhibited significant cytotoxic activity against human colon cancer (SW1116) and leukemia (K562) cell lines while compounds 1, 2 and 7 were only weakly or moderately active.

Aspergillus fumigatus CY018, an endophytic fungus in Cynodon dactylon as a versatile producer of new and bioactive metabolites.

Aspergillus fumigatus CY018 was recognized as an endophytic fungus for the first time in the leaf of Cynodon dactylon. By bioassay-guided fractionation, the EtOAc extract of a solid-matrix steady culture of this fungus afforded two new metabolites, named asperfumoid (1) and asperfumin (2), together with six known bioactive compounds including monomethylsulochrin, fumigaclavine C, fumitremorgin C, physcion, helvolic acid and 5alpha,8alpha-epidioxy-ergosta-6,22-diene-3beta-ol as well as other four known compounds ergosta-4,22-diene-3beta-ol, ergosterol, cyclo(Ala-Leu) and cyclo(Ala-Ile). Through detailed spectroscopic analyses including HRESI-MS, homo- and hetero-nuclear correlation NMR experiments (HMQC, COSY, NOESY and HMBC), the structures of asperfumoid and asperfumin were established to be spiro-(3-hydroxyl-2,6-dimethoxyl-2,5-diene-4-cyclohexone-(1,3')-5'-methoxyl-7'-methyl-(1'H, 2'H, 4'H)-quinoline-2',4'-dione) and 5-hydroxyl-2-(6-hydroxyl-2-methoxyl-4-methylbenzoyl)-3,6-dimethoxyl-benzoic methyl ester, respectively. All of the 12 isolates were subjected to in vitro bioactive assays against three human pathogenic fungi Candida albicans, Tricophyton rubrum and Aspergillus niger. As a result, asperfumoid, fumigaclavine C, fumitremorgin C, physcion and helvolic acid were shown to inhibit C. albicans with MICs of 75.0, 31.5, 62.5, 125.0 and 31.5 microg/mL, respectively.

Anti-Helicobacter pylori metabolites from Rhizoctonia sp. Cy064, an endophytic fungus in Cynodon dactylon.

A new benzophenone, named rhizoctonic acid (1), together with three known compounds monomethylsulochrin (2), ergosterol (3) and 3beta,5alpha,6beta-trihydroxyergosta-7,22-diene (4) were isolated through bioassay-guided fractionations from the culture of Rhizoctonia sp. (Cy064), an endophytic fungus in the leaf of Cynodon dactylon. The structure of the new acid 1 was elucidated to be 5-hydroxy-2-(2-hydroxy-6-methoxy-4-methylbenzoyl)-3-methoxybenzoic acid by a combination of spectral analyses. Furthermore, the structure of monomethylsulochrin 2 was confirmed by 13C-NMR analysis. All four metabolites were subjected to a more detailed in vitro assessment of their antibacterial action against five clinically isolated and one reference (ATCC 43504) Helicobacter pylori strains.

Inhibitory effects of flavonoids from Hypericum perforatum on nitric oxide synthase.

The inhibitory effects of six flavonoids from Hypericum perforatum were assessed spectrophotometrically using nitric oxide synthase (NOS) in blood and cerebral homogenate of rats. Of the assayed compounds, quercetin and hyperoside showed concentration-dependent enzyme inhibitory actions. The IC50 values of quercetin for inhibiting NOS in rat cerebral homogenate and blood were 63.06 and 57.54 microM, and those of hyperoside 56.23 and 158.49 microM, respectively. The competitive patterns were discerned with the inhibition of the two flavonoids on NOS in serum and cerebral homogenate (except a mixed type inhibition was observed with quercetin in inhibiting cerebral NOS). Furthermore, similar inhibitions were found for quercetin upon NOS in cerebral homogenate and blood. However, a stronger inhibitory effect of hyperoside on the enzyme was discerned in cerebrum than in blood. These results suggested that the galactose moiety in hyperoside may be associated with the selectivity of the NOS inhibition.

Inhibition of MAO A and B by some plant-derived alkaloids, phenols and anthraquinones.

A total of seventeen phytochemicals including seven alkaloids (piperine, strychnine, brucine, stachydrine, tetrandrine, frangchinoline and sinomenine), four phenols (paeonol, honokiol, magnolol and eugenol) and six anthraquinones (emodin, rhein, chrysorphanol, aloe-emodin, physcion and 1,8-dihydroxyanthraquinone) was examined for inhibitory activity of monoamine oxidase (MAO) A and B from rat brain mitochondrial. Among these compounds, piperine and paeonol were found to be inhibitory against MAO A in a dose-dependent manner with IC(50) values of 49.3 and 54.6 microM, respectively. Piperine, paeonol and emodin were shown to inhibit MAO B in a dose-dependent manner with the IC(50) data of 91.3, 42.5 and 35.4 microM, respectively. Lineweaver-Burk transformation of the inhibition data indicated that the inhibitory action of piperine on MAO A was of mixed type, and that of paeonol on the same type of the enzyme was of non-competitive type. For piperine, the K(i) and K(I) were determined to be 35.8 and 25.7microM, respectively. For paeonol, the K(i) was estimated to be 51.1 microM. The inhibition of piperine and paeonol on MAO B was of competitive type with K(i) values of 79.9 and 38.2 microM, respectively. The inhibition of emodin on MAO B was of mixed type with the K(i) and K(I) data of 15.1 and 22.9 microM, respectively. The present investigation showed that the phytochemicals piperine, paeonol and emodin are potent MAO inhibitors whereas other compounds were inactive against any type of MAO at 100 microM in the present assay.

The effects of high field strength MRI on electrodes and pulse generator in dynamic graciloplasty.

OBJECTIVE: Dynamic graciloplasty is a treatment for intractable faecal incontinence. A gracilis muscle is transposed around the anus and stimulated with an implanted pulse generator (IPG). This in vitro study was designed to determine the safety of MRI in patients with implanted electrodes and pulse generators for dynamic graciloplasty. METHODS: Temperatures were measured with fiberoptic probes around the devices in a cadaver model. Current was measured with an oscilloscope connected to electrodes and IPG. Movement and IPG parameter setting were observed before, during and after testing. RESULTS: Minor temperature increase under 1 degrees C were observed around the electrodes. Amplitudes measured were within the range of -1 and +1 Volt. No movement or changing of IPG parameters was noted. CONCLUSION: Changes noted are well within physiological ranges. Dynamic graciloplasty is not a contraindication for high field strength MRI.

A new oxoaporphine alkaloid from Sinofranchetia chinensis.

A new oxoaporphine alkaloid, sinofranine, was isolated from the stem of Sinofranchetia chinensis. The structure of the new alkaloid was elucidated by a combination of spectral methods (IR, MS, 1H and 13C-NMR, NOED and COSY).