The capacity of particles to increase allergic sensitization is predicted by particle number and surface area, not by particle mass.

Particle exposure has traditionally been monitored as mass concentration of PM10 (particles with an aerodynamic diameter less than 10 microm), more recently also as PM2.5. The mass concentration is strongly influenced by the large particles. Therefore, particle mass is a poor measure for characterizing the amount of the small, possibly more biologically potent particles. We used polystyrene particles (PSP) ranging in diameter from 0.0588 to 11.14 microm, carbon black (CB), and diesel exhaust particles (DEP), to study the adjuvant effect of particles on the immune response to the allergen ovalbumin (OVA) after sc injection into the footpad of BALB/cA mice. At a given mass dose, the small particles (0.0588 and 0.202 microm PSP, CB, and DEP) increased the allergen-specific IgE serum levels to a substantially higher degree than the larger particles (1.053, 4.64, and 11.14 microm PSP). Further, in the draining lymph node during the primary response, the fine particles (0.202 microm) with OVA increased cell numbers, expression of surface markers (CD19, MHC class II, CD86, and CD23) and ex vivo production of IL-4 and IL-10, whereas the largest (11.14 microm) particles did not. Linear regression analyses indicated that the IgE response was not predicted by particle mass (R2 = 0.06), but was predicted by the total particle surface area (R2 = 0.64), number of particles (R2 = 0.62), and particle diameter (R2 = 0.58). In conclusion, we found that fine particles exerted stronger adjuvant effects on allergic responses than larger particles at equal mass doses. Consequently, the dose described as total particle surface area or particle number predicts the adjuvant effect of particles better than the currently used particle mass.     

Constipation Is a Frequent Problem Associated with Vascular Complications in Patients with Type 2 Diabetes: A Cross-sectional Study

Objective Diabetes is recognized as an underlying disease of constipation. However, the prevalence of constipation varies according to the diagnostic criteria applied. We investigated the prevalence of constipation based on the new guideline for constipation in Japanese patients with type 2 diabetes and examined the relationship with the clinical background, including diabetic vascular complications. Methods Questionnaire surveys including items concerning the diagnosis and treatment status of constipation were administered to 410 patients with type 2 diabetes. Results Although 29% of the patients considered that they had experienced constipation (self-judged), only 14% had consulted a physician about constipation. The prevalence of chronic constipation based on the guideline was 26%. After including laxative users, constipation was finally found in 36%. Despite the use of laxatives (n=81), 51% of the patients were still diagnosed with chronic constipation. Patients with constipation (chronic constipation or laxative use) were significantly older and had a longer duration of diabetes than those without constipation. The body mass index (BMI) of patients with constipation (24.9±3.8 kg/m²) was significantly lower than that of those without constipation (26.3±4.6 kg/m²). Diabetic neuropathy (49% vs. 32%) and coronary heart disease (CHD) (27% vs. 13%) were significantly more frequent in the patients with constipation than in those without constipation. A multivariate logistic regression analysis revealed that gender, BMI, diabetic neuropathy, insulin use, and CHD were significantly associated with constipation. Conclusion An accurate diagnosis of constipation is desirable in patients with type 2 diabetes because constipation is independently associated with CHD.     

Simultaneous removal of organic matter and nitrogen compounds by partitioned aeration in a 226 L-scale microbial fuel cell

Although microbial fuel cells (MFCs) have been widely studied as wastewater treatment technologies that convert organic matter to electricity, there are few reports of large-scale MFCs that treat both organic matter and nitrogen compounds. In this study, a 226 L reactor equipped with 27 MFC units was partially aerated at 10% of its total volume. The MFC unit consists of a cylindrical air core covered with a carbon-based air cathode, an anion exchange membrane, and a graphite non-woven fabric anode. The air-cathode MFC with 13 L min⁻¹ aeration rate produced a current density of 0.0012–0.15 A m⁻² with 40 to >93% biological oxygen demand (BOD) removal to have an effluent BOD of <5–36 mg L⁻¹ at a hydraulic retention time (HRT) of 12–47 h. Meanwhile, 55 ± 17% of the total nitrogen (TN) was removed, resulting in 9.7 ± 3.8 mg L⁻¹ TN in the effluent, although the TN removal was limited at ≥20 °C. The mono-exponential regression for BOD and TN (≥20 °C) estimated that an HRT of 21 h could meet the Japanese effluent quality standards of BOD and TN. Calculation of the total energy recovered via current generation and energy consumed by aeration suggested an energy consumption of 0.22 kW h m⁻³. Decreasing the aeration rate and HRT in the reactor would further reduce energy consumption and increase energy production.

Partial aeration simultaneously removed organic matters and nitrogen compounds in a 226 L reactor equipped with 27 microbial fuel cells.     

Role of chymase on growth of cultured canine Tenon's capsule fibroblasts and scarring in a canine conjunctival flap model

Chymase is a chymotrypsin-like serine protease contained in the secretory granules of mast cells. Recently, we reported that chymase activity and the number of chymase-positive mast cells in conjunctival tissues were significantly increased during the wound healing process in a hamster model of glaucoma surgery. However, it has been unclear the role of chymase on conjunctival scarring. In the present study, we evaluated the effect of dog chymase on cell proliferation of fibroblasts established from canine Tenon's capsule and the effect of a chymase inhibitor on scarring in a canine conjunctival flap model. After a fibroblast cell culture was established from canine Tenon's capsules, the fibroblasts were incubated in the presence of dog chymase (5-20 ng ml(-1)). Cell proliferation was evaluated by bromodeoxyuridine incorporation. In a canine conjunctival flap model, a sponge treated with a chymase inhibitor, Suc-Val-Pro-Phe(P)(OPh)(2), or placebo was placed in between the conjunctiva and sclera and the conjunctival incision was closed. One week after the surgery, adhesion degree was assessed, and chymase activities in the conjunctival lesion and in the areas of the conjunctiva and sclera were measured. In cultured canine Tenon's capsule fibroblasts, dog chymase significantly increased cell proliferation, and this chymase-dependent proliferation was completely suppressed by the chymase inhibitor. In the canine surgical model, chymase activity in placebo-treated eyes was significantly increased compared to control eyes, while it was significantly decreased by treatment with the chymase inhibitor. Scores for adhesion degree in the chymase inhibitor-treated eyes were significantly decreased in comparison with those in placebo-treated eyes. The conjunctival area in the chymase inhibitor-treated eyes was also suppressed to 52.6% compared with that in placebo-treated treated eyes. In conclusion, chymase stimulates proliferation of fibroblasts derived from canine Tenon's capsule and chymase may play an important role in scarring after glaucoma surgery.     

Liquid chromatographic determination of hydralazine in human plasma with 2-hydroxy-1-naphthaldehyde pre-column derivatization

A selective and sensitive high-performance liquid chromatographic method is described for determination of hydralazine and its metabolites in human plasma. The method involves pre-column derivatization with 2-hydroxy-1-naphthaldehyde at pH 1.2. The reaction product and Methyl Red used as internal standard are extracted into dichloromethane and chromatographed in the reversed-phase mode on an ODS-2 column using acetonitrile—aqueous triethylamine phosphate buffer (80:20, v/v) at pH 3 as eluent.

The plasma calibration curve of hydralazine is linear in the concentration range 10–500 ng ml⁻¹. The detection limit is 1 ng ml⁻¹ and the relative standard deviation is <2.4. In vivo pharmacokinetics of hydralazine in two volunteers after oral administration of 50 mg of the drug is studied using the proposed LC method.     

Disinhibitory involvement of the anterior cingulate cortex in the descending antinociceptive effect induced by electroacupuncture stimulation in rats

The present study was conducted to clarify the role of the anterior cingulate cortex (ACCX) in acupuncture analgesia. Experiments were performed on 35 female Wistar albino rats weighing about 300 g. Single unit recordings were made from ACCX neurons with a tungsten microelectrode. Descending ACCX neurons were identified by antidromic activation from electrical shocks applied to the ventral part of the ipsilateral PAG through a concentric needle electrode. Cathodal electroacupuncture stimulation of Ho-Ku (0.1 ms in duration, 45 Hz) for 15 min was done by inserting stainless steel needles bilaterally. An anodal silver-plate electrode (30 mm x 30 mm) was placed on the center of the abdomen. Naloxone (1.0 mg/kg, i.v.) was used to test whether changes of ACCX activities were induced by the endogenous opioid system. Data were collected from a total of 73 ACCX neurons. Forty-seven neurons had descending projection to the PAG, and the other 26 had no projections to the PAG. A majority of descending ACCX neurons were inhibited by electroacupuncture stimulation. By contrast, non-projection ACCX neurons were mainly unaffected by electroacupuncture. Naloxone did not reverse acupuncture effects on the changes of ACCX neuronal activities. Acupuncture stimulation had predominantly inhibitory effects on the activities of descending ACCX neurons. Since the functional connection between ACCX and PAG is inhibitory, electroacupuncture caused disinhibition of PAG neurons, whose activity is closely related to descending antinociception to the spinal cord. This disinhibitory effect elicited by acupuncture stimulation is thought to play a significant role in acupuncture analgesia.     

The transitional phase of ductus venosus reversed flow in severely premature IUGR fetuses

The guiding hypothesis for this work is that in severe intrauterine growth-restricted (IUGR) fetuses, the time from ductus venosus (DV) reversed flow (RF) appearance to intrauterine fetal demise (IUFD) or nonreassuring fetal testing is variable. As such, there must be a transitional phase between the presence of end-diastolic forward flow (FF) and absent or reversed end-diastolic flow (A/REDF). Ductus venosus Doppler was serially studied in 19 IUGR fetuses (estimated fetal weight < 10th percentile and umbilical artery pulsatility index > 95th percentile) from diagnosis until demise or delivery occurring for nonreassuring fetal testing. Ductus venosus waveforms were assessed qualitatively: forward flow versus absent or reversed flow in diastole. Two sets of at least 30 consecutive ductus venosus waveforms were obtained at each examination. If the waveforms differed between the two sets, they were defined as alternating. Cord arterial pH and base excess (BE) were obtained at birth. In 14 cases, DVRF occurred intermittently between periods of FF during the same clinical visit. Intermittent DVRF was present from 2 to 57 days (median, 13 days) and became continuous from 1 to 23 days (median, 7 days) before the occurrence of delivery for nonreassuring fetal testing or fetal demise. One fetus had an abnormal arterial pH (< 7.0) and one had an abnormal BE (< -12). These data show that (1) there is a transitional phase in which DV alternates FF and A/RF before RF becomes persistent; (2) the time from the appearance of DVRF to delivery or IUFD is variable, and (3) not all very preterm IUGR fetuses with continuous DVRF are acidemic. Because of these findings, the decision of delivery regarding early severe IUGR fetuses should be individualized, and the DVRF Doppler information has to be integrated with other antenatal fetal parameters.