Elevated levels of substance P in tears of patients with allergic conjunctivitis and vernal keratoconjunctivitis

BACKGROUND: Recent studies have suggested that the nervous system may participate in inflammatory processes. Substance P (SP) acts as a chemical mediator as well as a neurotransmitter. OBJECTIVE: In order to clarify the pathogenesis of ocular allergic diseases, we assessed the concentration of SP in tears. METHODS: Using a highly sensitive and specific double-antibody enzyme immunoassay (EIA), we determined the SP concentration in tears of 10 patients with seasonal allergic conjunctivitis, 10 with atopic dermatitis without keratoconjunctivitis (AD), 13 with vernal keratoconjunctivitis (VKC) and 65 normal controls. Giemsa's staining for brush cytology samples and histocytological study by immunocytochemical staining of giant papillary conjunctival cells from VKC and normal controls was conducted. RESULTS: The mean SP level was low in the normal controls and AD, whereas patients with seasonal allergic conjunctivitis and VKC showed significant elevation of SP (P < 0.01). Brush cytology samples showed conjunctival epithelial cells with lymphocytes, neutrophils and eosinophils that were not seen in normal subjects. Histocytological examination demonstrated SP positive cells in the conjunctiva of patients with VKC, but not in normal controls. CONCLUSION: This study suggests that the increased level of SP in tears may contribute to the pathogenesis and severity of ocular allergic diseases.     

Combination phase I/II study of irinotecan hydrochloride (CPT-11) and carboplatin in relapsed or refractory non-Hodgkin's lymphoma. CPT-11/Lymphoma Study Group

Irinotecan hydrochloride (CPT-11) is a new derivative of camptothecin which inhibits topoisomerase I. Phase II studies have demonstrated that CPT-11 is active against a broad spectrum of neoplasms including intractable non-Hodgkin's lymphoma. An early phase II study in lymphoma suggested that a schedule of daily infusions of 40 mg/m2/day for three or five consecutive days is more effective than a single infusion of 200 mg/m2 every three to four weeks. Carboplatin is also an active agent against lymphoma, and preclinical studies have shown that CPT-11 and its active metabolite have a synergistic effect with platinum compounds. To evaluate the maximal tolerated dose (MTD) and the therapeutic efficacy of CPT-11 in combination with carboplatin in relapsed or refractory non-Hodgkin's lymphoma, we conducted a combination phase I/II study. The starting dose of CPT-11 was 20 mg/m2/day (days 1 through 3 and 8 through 10), and dose escalations of 5 mg/m2/day increments were planned, with a fixed dose of carboplatin (300 mg/m2, day 1). Six of the eight patients receiving both agents at the starting dose level developed critical toxicities such as grade 4 hematologic (neutropenia 6/8, thrombocytopenia 1/8) and grade 3 non-hematologic toxicities (diarrhea 2/8, transaminase elevation 1/8). Further dose escalation of CPT-11 was halted, and the starting doses were judged to be the MTDs. The response rate (25%, 2/8) to the combination of the MTDs was not superior to that of CPT-11 alone in a previous phase II study (38%, 26/69), and the MTD of CPT-11 in combination with carboplatin was less than half the single-agent dose. We conclude that carboplatin is not recommendable for combination with CPT-11 in lymphoma patients. Other suitable agents for such a combination should be sought.     

Valproic acid overdose and L-carnitine therapy

We examined the primary ischaemic changes in the pancreas in 35 patients with disseminated intravascular coagulation. In 7 (20%), multiple patchy lesions composed of degenerative acinar cells indicating coagulation necrosis were noted. None of these lesions was accompanied by fat necrosis. The patchy lesions involved the islets of Langerhans in only 1 case. The interlobular arteries of the pancreas near these lesions contained fibrin thrombi in all 7 cases. We suggest that these lesions, without fat necrosis, are the distinctive ischaemic change associated with disseminated intravascular coagulation.     

Efficacy of granisetron in the prevention of emesis induced by conditioning chemotherapy for allogeneic bone marrow transplantation

We conducted this study to compare granisetron, 5-HT3 antagonist, with conventional antiemetics in the prophylaxis of emesis induced by conditioning chemotherapy for allogeneic bone marrow transplantation in 41 patients. The conditioning chemotherapy regimen included either cytosine arabinoside 2 g/m2 x 4 and cyclophosphamide 60 mg/kg x 2 (CA, CY), or busulfan 4 mg/kg x 4 and cyclophosphamide 60 mg/kg x 2 (BU, CY). In CA and CY regimen, the clinical effective rate with granisetron against emesis was 94.1% on the 1st day, compared with 7.6% in the control group. On day 2 and 3, the effective rate with granisetron was 58.8% and 23.5%, respectively, compared with 0% in the control group. In the BU and CY regimen, control of emesis with granisetron on day 5 and 6 was 66.7%, against 20.0% in the control group. Based on these data, we concluded granisetron is superior to conventional antiemetics in the prophylaxis of emesis induced by conditioning for allogeneic bone marrow transplantation.     

Network structures and dynamics of dry and swollen poly(acrylate)s. Characterization of high- and low-frequency motions as revealed by suppressed or recovered intensities (SRI) analysis of C NMR

We recorded temperature-dependent high-resolution ¹³C NMR spectra of dry and swollen poly(acrylate)s [poly(2-methoxyethyl acrylate) (PMEA), poly(2-hydroxyethyl methacrylate) (PHEMA), and poly(tetrahydrofurfuryl acrylate) (PTHFA)] by dipolar decoupled-magic angle spinning (DD-MAS) and cross-polarization-magic angle spinning (CP-MAS) methods, to gain insight into their network structures and dynamics. Suppressed or recovered intensities (SRI) analysis of ¹³C CP-MAS and DD-MAS NMR was successfully utilized, to reveal portions of dry and swollen polymers which undergo fast and slow motions with fluctuation frequencies in the order of 10⁸ Hz and 10⁴-10⁵ Hz, respectively. Fast isotropic motions with frequency higher than 10⁸ Hz at ambient temperature were located to the portions in which ¹³C CP-MAS NMR signals of swollen PMEA were selectively suppressed. In contrast, low-frequency motion was identified to the portions in which ¹³C DD-MAS (and CP-MAS) signals are most suppressed at the characteristic suppression temperature(s) T_s. Network of PMEA gels (containing 7 wt% of water) turns out to be formed by partial association of backbones only, as manifested from their T_s gradient at lowered temperature, whereas networks of PHEMA (containing 40 wt% of water) and PTHFA (9 wt% of water) gels are tightly formed through mutual inter-chain associations of both backbones and side-chains, as viewed from the raised T_s values for both near at ambient temperature. It is also interesting to note that flexibility of gel network (PMEA > PTHFA > PHEMA) characterized by the suppression temperature T_s (PMEA < PTHFA < PHEMA) is well related with a characteristic parameter for biocompatibility such as the production of TAT (thrombin-antithrombin III complex) as a marker of activation of the coagulation system.     

Novel Enantiocomplementary C2‐Symmetric Chiral Bis(imidazoline) Ligands: Highly Enantioselective Friedel–Crafts Alkylation of Indoles with Ethyl 3,3,3‐Trifluoropyruvate

Enantioselective Friedel–Crafts alkylations of a variety of indoles with ethyl 3,3,3‐trifluoropyruvate catalyzed by novel chiral m‐phenylenebis(imidazoline)‐copper(II) complexes or the bis(imidazoline)‐achiral acid combination afforded products with high enantioselectivity. Both enantiomers of indole derivatives can be prepared with high enantioselectivities by tuning the N‐substituents of the imidazoline.     

Effect of chloride on the formation of 3-monochloro-1,2-propanediol fatty acid diesters and glycidol fatty acid esters in fish,meats and acylglycerols during heating

The effects of the presence of chloride on the formation of 3-monochloro-1,2-propanediol fatty acid esters (3-MCPDEs) and glycidol fatty acid esters (GEs) in saltwater fish, meats and acylglycerols (diacylglycerol and triacylglycerol) during heating were investigated in this study. Five saltwater fish species (salmon, saury, yellowtail, mackerel and Spanish mackerel) were grilled with a fish griller. 3-MCPDEs and GEs were detected in all of the grilled fish samples. The total amount of GEs was higher than 3-MCPDEs. Beef and pork patties with or without sodium chloride (1.5%) were cooked using gaseous fuel. The formation of 3-MCPDEs was significantly increased by the addition of sodium chloride to the meat patties, whereas the concentration of GEs in the cooked meat patties was not changed by the content of sodium chloride. Hexadecane solutions of diacylglycerol or triacylglycerol containing FeCl₃ were heated at 240°C. The formation of 3-MCPDEs was greatly increased by adding FeCl₃ to the solutions of triacylglycerol. The amounts of 3-MCPDEs decreased with the extension of the heating time. From these results, it is suggested that 3-MCPDEs and GEs are formed in saltwater fish and meats by cooking, and that the formation of 3-MCPDEs was affected by chloride in foodstuffs.     

Effects of Phosphoryl Oligosaccharides of Calcium (POs-Ca) on Mycelial Growth and Fruiting Body Development of the Edible Mushroom,Pleurotus ostreatus

Phosphoryl oligosaccharides of calcium (POs-Ca) is a calcium salt of phosphoryl maltooligosaccharides made from potato starch. POs-Ca is highly water-soluble and can supply both the calcium ion and acidic oligosaccharides in an aqueous solution. In this study, we investigated the effects of POs-Ca on the mycelial growth and fruiting body yield of Pleurotus ostreatus , which is one of the most widely cultivated edible mushrooms in the world. We cultivated the mushroom using both potato dextrose agar (PDA) medium and sawdust-based medium, with added calcium salts. The addition of POs-Ca into the PDA medium with a calcium concentration of 10 mg increased mycelial growth significantly ( p < 0.05, vs . control). POs-Ca addition to the sawdust-based medium at concentrations of 1.0 to 3.0 g/100 g medium increased the amount of calcium in the fruiting bodies but did not affect the length of the cultivation period or the weight of the fruiting body. The calcium content in the fruiting body increased 12-fold when compared to the control. On the other hand, neither the CaHPO ₄ ･2H ₂ O group nor the CaHPO ₄ ･2H ₂ O with oligosaccharides group showed changes in the calcium content of the fruiting bodies. Our results indicate that the use of POs-Ca in mushroom cultivation allows for the possibility of developing new functional foods like calcium-enriched edible mushrooms. This is the first report describing the effects of POs-Ca on mushroom cultivation.     

Nitric Oxide and Reactive Oxygen Species in the Pathogenesis of Preeclampsia

Preeclampsia (PE) is characterized by disturbed extravillous trophoblast migration toward uterine spiral arteries leading to increased uteroplacental vascular resistance and by vascular dysfunction resulting in reduced systemic vasodilatory properties. Its pathogenesis is mediated by an altered bioavailability of nitric oxide (NO) and tissue damage caused by increased levels of reactive oxygen species (ROS). Furthermore, superoxide (O₂⁻) rapidly inactivates NO and forms peroxynitrite (ONOO⁻). It is known that ONOO⁻ accumulates in the placental tissues and injures the placental function in PE. In addition, ROS could stimulate platelet adhesion and aggregation leading to intravascular coagulopathy. ROS-induced coagulopathy causes placental infarction and impairs the uteroplacental blood flow in PE. The disorders could lead to the reduction of oxygen and nutrients required for normal fetal development resulting in fetal growth restriction. On the other hand, several antioxidants scavenge ROS and protect tissues against oxidative damage. Placental antioxidants including catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx) protect the vasculature from ROS and maintain the vascular function. However, placental ischemia in PE decreases the antioxidant activity resulting in further elevated oxidative stress, which leads to the appearance of the pathological conditions of PE including hypertension and proteinuria. Oxidative stress is defined as an imbalance between ROS and antioxidant activity. This review provides new insights about roles of oxidative stress in the pathophysiology of PE.