Spatiotemporal calibration and resolution refinement of output from deterministic models

Spatiotemporal calibration of output from deterministic models is an increasingly popular tool to more accurately and efficiently estimate the true distribution of spatial and temporal processes. Current calibration techniques have focused on a single source of data on observed measurements of the process of interest that are both temporally and spatially dense. Additionally, these methods often calibrate deterministic models available in grid‐cell format with pixel sizes small enough that the centroid of the pixel closely approximates the measurement for other points within the pixel. We develop a modeling strategy that allows us to simultaneously incorporate information from two sources of data on observed measurements of the process (that differ in their spatial and temporal resolutions) to calibrate estimates from a deterministic model available on a regular grid. This method not only improves estimates of the pollutant at the grid centroids but also refines the spatial resolution of the grid data. The modeling strategy is illustrated by calibrating and spatially refining daily estimates of ambient nitrogen dioxide concentration over Connecticut for 1994 from the Community Multiscale Air Quality model (temporally dense grid‐cell estimates on a large pixel size) using observations from an epidemiologic study (spatially dense and temporally sparse) and Environmental Protection Agency monitoring stations (temporally dense and spatially sparse). Copyright © 2016 John Wiley & Sons, Ltd.     

Antispasmodic,bronchodilator and blood pressure lowering properties of Hypericum oblongifolium – possible mechanism of action

The crude extract of Hypericum oblongifolium (Ho.Cr), which tested positive for flavonoids, saponins and tannins caused concentration‐dependent (0.1–1.0 mg/mL) relaxation of spontaneous and high K⁺ (80 mM)‐induced contractions in isolated rabbit jejunum preparations, suggesting a Ca⁺⁺ antagonistic effect, which was confirmed when pretreatment of the tissue with Ho.Cr produced a rightward shift in the Ca⁺⁺ concentration‐response curves, like that caused by verapamil. Ho.Cr relaxed carbachol (1 μM) and high K⁺‐induced contractions in guinea pig tracheal preparations. It caused a dose‐dependent (3–100 mg/kg) fall in arterial blood pressure of rats under anesthesia. In isolated guinea pig atria, Ho.Cr caused inhibition of both atrial force and rate of spontaneous contractions. When tested in rabbit aortic rings, Ho.Cr exhibited a vasodilator effect against phenylephrine (1 μM) and high K⁺‐induced contractions. These results indicate that Ho.Cr possesses gastrointestinal, respiratory and cardiovascular inhibitory effects, mediated via a Ca⁺⁺ antagonist mechanism. Copyright © 2009 John Wiley & Sons, Ltd.     

Calcium channel blocking activity of Mentha longifolia L. explains its medicinal use in diarrhoea and gut spasm

Mentha longifolia has a reputation in traditional medicine in the indications of diarrhoea and gut spasm. This study was carried out to provide a possible pharmacological basis for its medicinal use in hyperactive gut disorders. In a castor oil induced diarrhoeal model, the crude extract of Mentha longifolia (Ml.Cr), at doses of 100–1000 mg/kg, provided 31–80% protection, similar to loperamide. In isolated rabbit jejunum preparations, Ml.Cr caused inhibition of spontaneous and high K⁺‐induced contractions, with respective EC₅₀ values of 1.80 (1.34–2.24; n = 6–8) and 0.60 mg/mL (0.37–0.85; n = 6–8), which suggests spasmolytic activity, mediated possibly through calcium channel blockade (CCB). The CCB activity was further confirmed when pretreatment of the tissue with Ml.Cr (0.3–1 mg/mL) caused a rightward shift in the Ca⁺⁺ concentration–response curves (CRCs), similar to verapamil. Loperamide also inhibited spontaneous and high K⁺‐induced contractions and shifted the Ca⁺⁺ CRCs to the right. Activity‐directed fractionation revealed that the petroleum spirit fraction was more potent than the parent crude extract and aqueous fraction. These data indicate that the antidiarrhoeal and spasmolytic effects of the crude extract of Mentha longifolia are mediated through the presence of CCB‐like constituent(s), concentrated in the petroleum spirit fraction and this study provides indirect evidence for its medicinal use in diarrhoea and spasm. Copyright © 2010 John Wiley & Sons, Ltd.     

Spermatogenesis disorder is associated with mutations in the ligand‐binding domain of an androgen receptor

Androgens play a key role in spermatogenesis, and their functions are mediated by the androgen receptor (AR). Some mutations in the AR gene have the potential to alter the primary structure and function of the protein. The aim of this study was to investigate the AR gene mutations in a cohort of males with idiopathic azoospermia referred to Royan Institute. Fifty‐one biopsy samples were obtained for routine clinical purposes from 15 men with hypospermatogenesis (HS), 17 patients with maturation arrest (MA) and 19 patients with Sertoli cell‐only syndrome (SCOS). The AR cDNAs were prepared from tissue mRNAs and were sequenced. One synonymous variant and three nonsynonymous protein coding single nucleotide polymorphisms (nsSNPs) were detected. Protein structure prediction demonstrated that the S815I and M746T nonsynonymous variants would affect protein structure and its normal function. Our study suggests that mutations in the AR gene would change or disturb the receptor's normal activity. Although these variations may influence spermatogenesis, it is difficult to say that they lead to a lack of spermatogenesis.     

Polyp detection rates using magnification with narrow band imaging and white light

AIM: To compare the yield of adenomas between narrow band imaging and white light when using high definition/magnification. METHODS: This prospective, non-randomized comparative study was performed at the endoscopy unit of veteran affairs medical center in Phoenix, Arizona. Consecutive patients undergoing first average risk colorectal cancer screening colonoscopy were selected. Two experienced gastroenterologists performed all the procedures that were blinded to each other's findings. Demographic details were recorded. Data are presented as mean ± SEM. Proportional data were compared using the χ2 test and means were compared using the Student's t test. Tandem colonoscopy was performed in a sequential and segmental fashion using one of 3 strategies: white light followed by narrow band imaging [Group A: white light(WL) → narrow band imaging(NBI)]; narrow band imaging followed by white light(Group B: NBI → WL) and, white light followed by white light(Group C: WL → WL). Detection rate of missed polyps and adenomas were evaluated in all three groups. RESULTS: Three hundred patients were studied(100 in each Group). Although the total time for the colonoscopy was similar in the 3 groups(23.8 ± 0.7, 22.2 ± 0.5 and 24.1 ± 0.7 min for Groups A, B and C, respectively), it reached statistical significance between Groups B and C(P 0.05). The cecal intubation time in Groups B and C was longer than for Group A(6.5 ± 0.4 min and 6.5 ± 0.4 min vs 4.9 ± 0.3 min; P 0.05). The withdrawal time for Groups A and C was longer than Group B(18.9 ± 0.7 min and 17.6 ± 0.6min vs 15.7 ± 0.4 min; P 0.05). Overall miss rate for polyps and adenomas detected in three groups during the second look was 18% and 17%, respectively(P = NS). Detection rate for polyps and adenomas after first look with white light was similar irrespective of the light used during the second look(WL → WL: 13.7% for polyps, 12.6% for adenomas; WL → NBI: 14.2% for polyps, 11.3% for adenomas). Miss rate of polyps and adenomas however was significantly higher when NBI was used first(29.3% and 30.3%, respectively; P 0.05). Most missed adenomas were ≤ 5 mm in size. There was only one advanced neoplasia(defined by size only) missed during the first look. CONCLUSION: Our data suggest that the tandem nature of the procedure rather than the optical techniques was associated with the detection of additional polyps' and adenomas.     

Synthesis and in vitro antimicrobial evaluation of condensed heterocyclic 6-substituted 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole and 1,3,4-oxadiazole derivatives of isoniazid

A series of 6-substituted-1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole (3a-g) and 1,3,4-oxadiazole (4a-g, 5) derivatives of isoniazid were synthesized in satisfactory yield and pharmacologically evaluated for their in vitro antimicrobial activity. All the synthesized compounds were in good agreement with elemental and spectral data. A majority of the tested compounds showed good to moderate antimicrobial activity against all tested pathogenic bacterial and fungal strains.     

Antiurolithic effect of berberine is mediated through multiple pathways

Berberine is an isoquinoline alkaloid, occurring in nature as the main constituent of several plants with medicinal use in kidney stone disease. This work was undertaken to evaluate its antiurolithic potential and explore the possible underlying mechanism(s). Berberine was tested in vitro for the antioxidant effect and in vivo for diuretic and antiurolithic effects on an animal model of calcium oxalate urolithiasis. Berberine exhibited concentration-dependent (50-150μg/ml) antioxidant effect against ferrous-ascorbate induced lipid peroxidation in rat kidney homogenate with potency slightly higher than the reference antioxidant, butylated hydroxytoluene. In Wistar rats, berberine (5-20mg/kg) increased urine output accompanied by increased pH and Na(+) and K(+) excretion and decreased Ca(2+) excretion, similar to hydrochlorothiazide. In an animal model of calcium oxalate urolithiasis developed in male Wistar rats by adding 0.75% ethylene glycol in drinking water, berberine (10mg/kg) prevented as well as eliminated calcium oxalate crystal deposition in renal tubules and protected against deleterious effects of lithogenic treatment including weight loss, impaired renal function and oxidative stress, manifested as increased malondialdehyde and protein carbonyl contents, depleted GSH and decreased antioxidant enzyme activities of the kidneys. In na?ve rats, berberine (10mg/kg) increased urine volume and pH and decreased Ca(2+) excretion. Results of this study suggest the presence of antiurolithic effects in berberine against calcium oxalate stones mediated through a combination of antioxidant, diuretic, urinary alkalinizing and hypocalciuric effects. These data invite future studies on berberine to establish its efficacy for clinical use.     

Studies on the chemical composition and possible mechanisms underlying the antispasmodic and bronchodilatory activities of the essential oil of <Emphasis Type="Italic">Artemisia maritima</Emphasis> L.

This study describes the chemical composition of the essential oil of Artemisia maritima (Am.Oil) and the pharmacological basis for its medicinal use in gut and airways disorders. Twenty five compounds, composing 93.7% of the oil, were identified; among these, chrysanthenyl propionate and elixene were identified for the first time from any Artemisia species. The Am.Oil (0.3–1.0 mg/mL) suppressed spontaneous and high K⁺ (80 mM)-induced contractions in isolated rabbit jejunum, suggestive of an antispasmodic effect mediated possibly through calcium channel blockade. The calcium channel blockade activity was confirmed when pre-treatment of the tissue with Am.Oil (0.01–0.03 mg/mL) shifted the Ca⁺⁺ concentration-response curves to the right, similar to verapamil and papaverine. In isolated tracheal strips, Am.Oil inhibited carbachol (CCh; 1 μM)-induced contractions more than that induced by K⁺ and shifted the isoprenaline-induced inhibitory CRCs to the left, similar to papaverine, suggestive of potentiation, while, verapamil was more potent against K⁺ than CCh-induced contractions and had no potentiating effect on isoprenaline-induced inhibitory CRCs. These data indicate that the Am.Oil exhibited spasmolytic and bronchodilator activities mediated possibly through dual blockade of calcium channels and phosphodiesterase, which provides the pharmacological basis to the medicinal use of Artemisia maritima in colic, diarrhea and possibly asthma.     

Mechanisms underlying the antidiarrheal,antispasmodic and bronchodilator activities of Fumaria parviflora and involvement of tissue and species specificity

Ethnopharmacological relevance: In the Greco-Arab (Unani) traditional medicine, Fumaria parviflora Linn. is widely used in hypreractive gut and respiratory disorders including diarrhea, abdominal cramps, indigestion and asthma but scientific studies to provide rational for these medicinal uses are sparse. This study was therefore undertaken to provide ethnopharmacological basis for its medicinal use in diarrhea, abdominal cramps and asthma.