EFFECT OF ABDOMINAL IRRADIATION IN MICE MODEL OF INFLAMMATORY BOWEL DISEASE.

Inflammatory bowel diseases could be diagnosed in major measure by diagnostic imaging; however, radiation exposure in the intestine may also contribute to the progression of these pathologies. To better understand the impact of radiation in the presence of bowel disease, we administered dextran sodium sulfate (DSS) to C57BL/6 mice to induce colitis and exposed to radiation at abdominal area. We observed that abdominal irradiation (13 Gy) aggravates the DSS-induced decrease in survival rate (0%), body weight (74.54 ± 3.59%) and colon length (4.98 ± 0.14 cm). Additionally, abdominal irradiation markedly increased in colonic inflammation levels (3.16 ± 0.16) compared with that of DSS-induced sham mice. Furthermore, abdominal irradiation also increased the mRNA expression levels of inflammatory genes, such as cyclooxygenase-2 (13.10 folds), interleukin-6 (48.83 folds) and tumor necrosis factor-alpha (42.97 folds). We conclude that abdominal irradiation aggravates the detrimental effects of DSS-induced colitis in mice, which might be a useful guideline for inflammatory bowel disease patients.

The dependence of the electrophoretic mobility of small organic ions on ionic strength and complex formation.

The ionic strength dependence of the electrophoretic mobility of small organic anions with valencies up to -3 is investigated in this study. Provided the anions are not too aspherical, it is argued that shape and charge distribution have little influence on mobility. To a good approximation, the electrophoretic mobility of a small particle should be equal to that of a model sphere with the same hydrodynamic radius and same net charge. For small ions, the relaxation effect (distortion of the ion atmosphere from equilibrium due to external electric and flow fields) is significant even for monovalent ions. Alternative procedures of accounting for the relaxation effect are examined. In order to account for the ionic strength dependence of a specific set of nonaromatic and aromatic anions in aqueous solution, it is necessary to include complex formation between the anion with species in the BGE. A number of possible complexes are considered. When the BGE is Tris-acetate, the most important of these involves the complex formed between anion and Tris, the principle cation in the BGE. When the BGE is sodium borate, an anion-anion (borate) complex appears to be important, at least when the organic anion is monovalent. An algorithm is developed to analyze the ionic strength dependence of the electrophoretic mobility. This algorithm is applied to two sets of organic anions from two independent research groups.

Alteration in metabolism and toxicity of acetaminophen upon repeated administration in rats.

Our previous studies showed that administration of a subtoxic dose of acetaminophen (APAP) to female rats increased generation of carbon monoxide from dichloromethane, a metabolic reaction catalyzed mainly by cytochrome P450 (CYP) 2E1. In this study we examined the changes in metabolism and toxicity of APAP upon repeated administration. An intraperitoneal dose of APAP (500 mg/kg) alone did not increase aspartate aminotransferase, alanine aminotransferase, or sorbitol dehydrogenase activity in serum, but was significantly hepatotoxic when the rats had been pretreated with an identical dose of APAP 18 h earlier. The concentrations and disappearance of APAP and its metabolites in plasma were monitored for 8 h after the treatment. APAP pretreatment reduced the elevation of APAP-sulfate, but increased APAP-cysteine concentrations in plasma. APAP or APAP-glucuronide concentrations were not altered. Administration of a single dose of APAP 18 h before sacrifice increased microsomal CYP activities measured with p-nitrophenol, p-nitroanisole, and aminopyrine as probes. Expression of CYP2E1, CYP3A, and CYP1A proteins in the liver was also elevated significantly. The results suggest that administration of APAP at a subtoxic dose may result in an induction of hepatic CYP enzymes, thereby altering metabolism and toxicological consequences of various chemical substances that are substrates for the same enzyme system.

Association of carotid hemodynamics with risk of coronary heart disease in a Taiwanese population with essential hypertension.

BACKGROUND: The resistive index (RI) of the carotid artery is a hemodynamic parameter that depends on the degree of vascular resistance in hypertensive patients. The pulsatility index (PI) of the carotid artery was shown to be associated with microangiopathy in diabetic patients. In contrast to carotid intima-media thickness (IMT), no study has yet applied the carotid RI and PI to estimate coronary heart disease (CHD) risk. METHODS: Framingham risk scores (FRS) were determined for 62 patients (32 women; mean age 65 years (range 35-83)) with essential hypertension. Duplex sonography of the common carotid artery (CCA) was performed, with determination of RI, PI, and IMT. RESULTS: The mean FRS of all patients was 14.3% (range 1-30%), the mean IMT value of CCA was 0.89 +/- 0.23 mm, the mean RI was 0.71 +/- 0.07, and the mean PI was 1.46 +/- 0.39. FRS was found to have highly significant correlations with RI and PI (r = 0.47, P < 0.001 and r = 0.45, P < 0.001, respectively). The correlation between FRS and IMT was also significant (r = 0.41, P = 0.001). Multiple stepwise regression analysis showed that RI was an independent determinant of the risk of CHD. CONCLUSIONS: Although RI indirectly reflected the atherosclerotic process, the correlation between RI and CHD risk was comparable to the well-known correlation between cardiovascular event and carotid IMT. Hence, carotid RI can be used as a tool for risk stratification in Taiwanese patients with essential hypertension.

Association between hemodynamics in the common carotid artery and severity of carotid atherosclerosis in patients with essential hypertension.

BACKGROUND: Carotid intima-media thickness (IMT) and plaque burden evaluated by B-mode ultrasound have been used as relevant indicators for carotid atherosclerosis. This study was aimed to investigate the relationship between hemodynamic parameters in the common carotid artery (CCA) and the severity of carotid atherosclerosis in untreated hypertensive patients. METHODS: Carotid IMT and plaque burden were evaluated in bilateral CCA, bifurcations, external and internal carotid arteries using duplex ultrasound in 80 untreated hypertensive patients. The patients were divided into four groups according to plaque burden. Hemodynamic parameters of CCA, including peak and mean circumferential wall tension (CWT), tensile stress (TS), wall shear stress (WSS), and Young's elastic modulus (YEM), were calculated after measurements of internal diameter (ID), IMT, and peak and mean flow velocities of CCA. Arterial stiffness was also assessed using the brachial-ankle pulse wave velocity (baPWV). RESULTS: Age, pulse pressure, creatinine, carotid IMT, and mean TS were shown to have significant differences among the four plaque groups (P < 0.05). Peak CWT and peak TS were also shown to have marginal differences. In univariate analysis, the peak and mean CWT and TS were significantly correlated with plaque score. Stepwise multiple regression analysis showed that carotid IMT, age, and peak CWT were independently associated with plaque score. CONCLUSIONS: These results suggest that the CWT and TS of the CCA are associated with the severity of carotid atherosclerosis in untreated hypertensive patients. Hence, the hemodynamics of vessels may contribute to the plaque burden of low-resistance arteries.

Critical Manifestations of Pneumoscrotum.

INTRODUCTION: Pneumoscrotum is a critical, physical finding that may indicate significant morbidity and mortality. Accumulation of gas in the scrotum can be primary or secondary. OBJECTIVE: This paper discusses rapid diagnosis and treatment options. MATERIAL AND METHODS: PubMed searches for pneumoscrotum, etiology, diagnosis, and treatment. RESULTS: We review the historical perspective, classification, etiology, diagnosis, and treatment options of pneumoscrotum, as well as the presentation of pneumoscrotum in neonates/infants. CONCLUSION: It is crucial to diagnose the etiology pneumoscrotum and designing a treatment option based off that.

Clinical Pathology of Bartholin's Glands: A Review of the Literature.

The Bartholin's glands are located symmetrically at the posterior region of the vaginal opening and play an important role in the female reproductive system. These two pea-sized glands are involved in mucus secretion and vaginal lubrication. Cyst formation in the glands is common and results from mucus build-up in gland ducts. It is important to monitor such cysts because they may occur in the form of carcinomas. Larger cysts and abscesses are found in the lower vestibular region and typically present with erythema and edema. Biopsy is an effective method for distinguishing between Bartholin's gland cysts and differential diagnosis. While smaller cysts may be asymptomatic and may be left untreated, larger cysts require medical attention. Several treatment options are available, including marsupialization and CO2 laser. Healing and recovery depend on the severity of infection and course of treatment.

Viscosity of dilute model bead arrays at low shear: inclusion of short range solute-solvent interactions.

The intrinsic viscosity, [eta], of certain polymer-solvent systems, such as alkanes in benzene, are "anomalous" in the sense that [eta] for low molecular weight fractions are low and in certain cases negative (Dewan, K. K.; Bloomfield, V. A.; Berget, P. G.; J. Phys. Chem. 1974, 75, 3120). In this work, the theory of the viscosity of a dilute suspension of macromolecules at low shear is formulated that accounts for possible solute-solvent interactions. In doing so, we show that negative intrinsic viscosities are possible and are able to reproduce quite well the known length dependence of [eta] for alkanes in benzene. The coarse grained, solvent continuum, bead model developed here is an extension of previous work (Allison, S. A.; Pei, H. J. Phys. Chem. B 2009, 113, 8056). Following Fixman (Fixman, M. J. Chem. Phys. 1990, 92, 6858), we assume that solute-solvent interactions are short-range in character and can be separated from long-range hydrodynamic interactions between different beads. These interactions are accounted for by introducing three adjustable parameters specific to the transport of small "monomeric" solutes in the solvent of interest. Long range hydrodynamic interactions are accounted for to order a(J)(2)/r(IJ)(3) (a(J) is a bead radius and r(IJ) is an interbead distance). In modeling a macromolecule as an arbitrary array of N beads, the transport of the array is examined numerically in 5 different elementary shear fields. The most computationally demanding component of the procedure involves the inversion of a 12N by 12N matrix. In the present work, we restrict ourselves to systems with a maximum N of about 100. Our procedure is first applied to short rods and rings of from 2 to 10 beads which can be compared with independent results from the literature. Agreement is found to be better than 5%. Modeling macromolecules as wormlike chains, the procedure is then applied first to duplex DNA and then to alkanes in benzene. In both cases, it is possible to obtain excellent agreement between modeling and experiment.

Induction of hepatic CYP2E1 by a subtoxic dose of acetaminophen in rats: increase in dichloromethane metabolism and carboxyhemoglobin elevation.

Dichloromethane (DCM) is metabolically converted to carbon monoxide mostly by CYP2E1 in liver, resulting in elevation of blood carboxyhemoglobin (COHb) levels. We investigated the effects of a subtoxic dose of acetaminophen (APAP) on the metabolic elimination of DCM and COHb elevation in adult female rats. APAP, at 500 mg/kg i.p., was not hepatotoxic as measured by a lack of change in serum aspartate aminotransferase, alanine aminotransferase, and sorbitol dehydrogenase activities. In rats pretreated with APAP at this dose, the COHb elevation resulting from administration of DCM (3 mmol/kg i.p.) was enhanced significantly. Also blood DCM levels were reduced, and its disappearance from blood appeared to be increased. Hepatic CYP2E1-mediated activities measured with chlorzoxazone, p-nitrophenol, and p-nitroanisole as substrates were all induced markedly in microsomes of rats treated with APAP. Aminopyrine N-demethylase activity was also increased slightly, but significantly. Western blot analysis showed that APAP treatment induced the expression of CYP2E1 and CYP3A proteins. Neither hepatic glutathione contents nor glutathione S-transferase activity was changed by the dose of APAP used. The results indicate that, contrary to the well known hepatotoxic effects of this drug at large doses, a subtoxic dose of APAP may induce CYP2E1, and to a lesser degree, CYP3A expression. This is the first report that APAP can increase cytochrome P450 (P450)-mediated hepatic metabolism and the resulting toxicity of a xenobiotic in the whole animal. The pharmacological/toxicological significance of induction of P450s by a subtoxic dose of APAP is discussed.