瑞格列奈与迪沙片治疗新诊断2型糖尿病的疗效对比观察

比较对新诊断2型糖尿病患者应用瑞格列奈（11例）和迪沙片（10例）治疗4周后空腹血糖（FPG）、餐后2h血糖（2hPG）、晨3点血糖（3aPG）,空腹胰岛素（FIns）、餐后2h胰岛素（2hIns）,糖化白蛋白的值。结果显示,与迪沙片组相比,瑞格列奈组治疗后空腹血糖、餐后2h血糖的下降幅度更为明显,但低血糖的发生次数反而减少。     

Histopathological characterisation of effects of the mouse Pax6 missense mutation on eye development

Mutations in PAX6/Pax6 lead to a variety of ocular anomalies in humans and mice. The aim of the study was to characterise the ocular abnormalities caused by the missense Pax6^Leca4 mutation and compare them to published observations on Pax6 alleles that are functionally equivalent to Pax6⁻ null alleles (such as Pax6^Sey and Pax6^Sey-Neu) and human inherited eye diseases. Ocular features of homozygous Pax6^Leca4/Leca4 and heterozygous Pax6^Leca4/+ embryos at E12.5-E18.5, heterozygous Pax6^Leca4/+ young mice at P18 and heterozygous Pax6^Leca4/+ adults at 12 weeks were analysed histologically with their wild-type Pax6^+/+ littermates. Homozygous Pax6^Leca4/Leca4 fetuses died perinatally with no eyes although an optic cup rudiment with pigmented cells developed. Pax6^Leca4/+ mice were microphthalmic and a range of other severe ocular phenotypes affected both the anterior and the posterior segments. In contrast to Pax6^+/−, the Pax6^Leca4/+ eyes had no goblet cells in the corneal epithelium, the iris was not hypoplastic and there was no lens-corneal epithelial plug. However, microphthalmia was more severe, corneal vascularisation occurred earlier (during fetal stages), pigmented cells were present in the vitreous and corneal stroma and the ciliary body was malformed or abnormal. These results show that, although Pax6^Leca4/+ lacked some eye abnormalities commonly seen in Pax6^Sey/+ and Pax6^Sey-Neu/+ eyes, in most respects their eyes were more severely affected. These differences probably reflect both differences between the Pax6^Leca4 and the Pax6^Sey-Neu mutations and differences in modifier gene expression in different genetic backgrounds. The presence of pigmented cells in the cornea is a novel observation. Some Pax6^Leca4/+ ocular abnormalities were similar to those present in human Peters' anomaly and persistent hyperplastic primary vitreous (PHPV) so Pax6^Leca4/+ mice provide a useful model for some inherited eye diseases.     

TGF-β and IL-17 serum levels and specific immunotherapy

Two new T cell subsets may be involved in allergic rhinitis (AR) pathogenesis: Th17 and T regulatory cells, mainly producing IL-17 and TGF-β respectively. Successful Sublingual Immunotherapy (SLIT) induces relevant immunological changes, thus the aim of this study was to evaluate serum IL-17 and TGF-β levels in AR patients treated with SLIT for 2 years. Patients' blood samples were collected before initiating SLIT (baseline), three months after the end of the first pre-seasonal SLIT course, and at the end of the second pre-seasonal course. IL-17 was detectable only in the most severe allergic patients. SLIT significantly induced an increase in serum TGF-β levels. There was moreover a significant relationship between TGF-β and symptom severity and drug use at the end of the study. Therefore, this study provides clinically relevant evidence that two pre-seasonal SLIT courses may significantly affect serum TGF-β levels.     

Time and cost involved in the care of newly registered patients with diabetes mellitus and other lifestyle diseases at diabetes clinics in Japan (JDDM 4).

AIMS: To study the time and cost involved in the care of newly registered outpatients with Type 2 diabetes mellitus (DM), compared with patients with hypertension and/or hyperlipidaemia (HTL). METHODS: A total of 313 patients with DM and 58 patients with HTL without diabetes were registered on their first visits to 11 diabetes clinics across Japan. The time and cost involved in their care was recorded over the following 5 months. RESULTS: In the first 3 months, there was an extensive time commitment to both groups. The time spent by physicians was 1.5 times longer for DM than for HTL. The total care time spent by all the care providers for DM was twice that for HTL. The cost of DM care was twice that for HTL, with the cost of medicines excluded. However, half of the cost for DM was for laboratory tests. When these were excluded, and the remaining cost divided by the time spent, the amount for DM was half of that for HTL. Over the 5 months, mean glycated haemoglobin (HbA(1c)) in DM patients improved from 8.0% to 6.5%, and 72% of DM patients achieved the glycaemic target of HbA(1c) < or = 6.5%. CONCLUSIONS: DM care in a diabetes clinic requires a great deal more time and resources than HTL to achieve the best outcome. An educational system for self care, presently lacking in the primary care setting in Japan, would improve glycaemic control for DM patients in the community.     

Flavocoxid is as effective as naproxen for managing the signs and symptoms of osteoarthritis of the knee in humans: a short-term randomized,double-blind pilot study

Flavocoxid (Limbrel), a proprietary mixture of flavonoid molecules (baicalin and catechin), was tested against a traditional nonsteroidal anti-inflammatory drug, naproxen, for the management of the signs and symptoms of moderate osteoarthritis (OA) in humans. Discomfort and global disease activity were used as the primary end points, and safety assessments were also taken for both treatments as a secondary endpoint. In this double-blind study, 103 subjects were randomly assigned to receive either flavocoxid [500 mg twice daily (BID)] or naproxen (500 mg BID) in a 1-month onset of action trial. Outcome measures included the short Western Ontario and McMaster University Osteoarthritis Index, subject Visual Analogue Scale for discomfort and global response, and investigator Visual Analogue Scale for global response and fecal occult blood. Both flavocoxid and naproxen showed significant reduction in the signs and symptoms of knee OA (P ≤ .001). There were no statistically detectable differences between the flavocoxid and naproxen groups with respect to any of the outcome variables. Similarly, there were no statistically detectable differences between the groups with respect to any adverse event, although there was a trend toward a higher incidence of edema and nonspecific musculoskeletal discomfort in the naproxen group. In this short-term pilot study, flavocoxid was as effective as naproxen in controlling the signs and symptoms of OA of the knee and would present a safe and effective option for those individuals on traditional nonsteroidal anti-inflammatory drugs or cyclooxygenase-2 inhibitors. A low incidence of adverse events was reported for both groups.     

Chronic GVHD in minor salivary glands and oral mucosa: histopathological and immunohistochemical evaluation of 25 patients

BACKGROUND: Graft-vs.-host disease (GVHD) is the major cause of morbidity and mortality in patients undergoing allogeneic Bone Marrow Transplantation (BMT). The aim of our study was to identify the most relevant histological features for diagnosis of chronic Graft-vs.-Host Disease (cGVHD) in oral mucosa and minor salivary glands of 25 patients, as well as to evaluate the immunophenotype of the inflammatory cells. METHODS: Sixteen patients that were submitted to allogeneic BMT but did not present cGVHD were selected as a control group. The sections were studied on H & E and CD68, CD45, CD4, CD8, CD20 staining. RESULTS: The most frequent histologic findings in oral mucosa at the day of diagnosis of cGVHD were: hydropic degeneration of the basal layer of the epithelium, apoptotic bodies, lymphocytic infiltration, and focal or total cleavage between the epithelial and connective tissue. In the labial salivary glands (LSG), lymphocytic infiltration, acinar loss and fibrosis were the main alterations. Cytotoxic CD8-T cells and macrophages were predominant both in the epithelium and connective tissue, as well as in minor salivary glands. CONCLUSIONS: Histological features were useful in the diagnosis of oral cGVHD. It is suggested that CD8-T cells and macrophages play important role in the pathogenesis of the disease.     

Cerebral type 2 astroglia are heterogeneous with respect to their ability to respond to neuroligands linked to calcium mobilization.

Very little information is available concerning the pharmacology of type 2 astroglia. During the past decade it has become apparent that two distinct lineages of astroglial cells can be defined in vitro. These two lineages are commonly referred to as type 1 and type 2 and are distinguished from each other on the basis of their morphological features and antigenic phenotypes. In contrast to type 1 astroglia, very little is known about the pharmacology of type 2 astroglia. The lack of information concerning the responsiveness of these cells stems primarily from difficulties encountered in isolating large numbers of type 2 astroglia free of other cell types. In the present study video- and photometer-based imaging systems were used to monitor the influence of a series of neuroligands on the intracellular calcium levels of individual cerebral type 2 astroglia in order to assess their expression of calcium-mobilizing receptors. The responses of 85 immunocytochemically identified cerebral type 2 astroglia to bradykinin (BK), norepinephrine (NE), histamine (HIST), carbachol (CARB), 2-methyl-thio ATP (2MT-ATP), glutamate (GLUT), and serotonin (5-HT) were analyzed. Approximately 50% of cerebral type 2 astroglia responded to BK, NE, HIST, CARB, and 2MT-ATP whereas only 16% and 9% of the cells responded to GLUT and 5-HT, respectively. The number of neuroligands that increased calcium in individual cells ranged from 0 to 6. These responses are quite similar to those previously demonstrated in cultured cerebral type 1 astroglia. No pattern of receptor co-expression was observed for the different neuroligands tests.(ABSTRACT TRUNCATED AT 250 WORDS)     

Monoclonal antibody production to human and bovine 2′:3′-cyclic nucleotide 3′-phosphodiesterase (CNPase): high-specificity recognition in whole brain acetone powders and conservation of sequence between CNP1 and CNP2

Monoclonal antibodies against human and bovine 2′:3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) were generated by fusing FOX-NY myeloma cells with spleen cells from RBF/Dn mice previously immunized with the purified brain antigens. The enzyme isolated from bovine brain was quite basic, with an isoelectric point of 9.71 and both the bovine and human enzymes consisted of a closely spaced doublet at approximately 44 and 46 kDa on SDS-PAGE. Six monoclonals were identified as strongly recognizing the enzyme on both ELISA plates and on immunoblots of whole brain protein. Four monoclonals very weakly cross-reacted with guinea pig myelin basic protein. In contrast with two previous reports, some of our monoclonal antibodies did immunostain 2 or 3 protein bands in peripheral nerve, two bands closely corresponding to those immunostained in central nervous system (CNS) myelin, the Wolfgram protein fraction and in acetone powders of whole brain. Each of the 6 monoclonals reacting strongly on immunoblots recognized the enzyme in from 2 to 5 of the species examined (human, bovine, rat, mouse and rabbit). In addition, all 6 monoclonals that immunostained the enzyme in whole brain, myelin and Wolfgram protein immunoblots recognized both CNP1 (44 kDa) and CNP2 (46 kDa). The two closely spaced protein bands observed on SDS-PAGE and previously stained on immunoblots of CNS CNPase using polyvalent rabbit anti-bovine CNPase antisera, and now different monoclonal antibodies, appear to be immunologically related and to contain highly conserved sequences.     

Association between cord blood IgE and genetic polymorphisms of interleukin-4, the β-subunit of the high-affinity receptor for IgE, lymphotoxin-α, and tumor Necrosis factor-α

High cord blood immunoglobulin E (cbIgE) is known to be associated with increased risks of atopic diseases in childhood. The relationship between genetic polymorphisms and high cbIgE has not been well documented. A cross-sectional study was conducted to assess the association between cbIgE and genetic polymorphisms of interleukin (IL)-4 -590C/T, the beta-subunit of the high-affinity receptor for IgE (FcepsilonRI-beta) E237G, lymphotoxin (LT)-alphaNcoI alleles, and tumor necrosis factor (TNF)-alpha -308G/A. A total of 320 mother-neonate pairs were recruited from four maternity hospitals from different locations of Taiwan. Cord blood was obtained and assayed for cbIgE. Polymerase chain reaction followed by restriction fragment length polymorphism was used to assess the genotypes. Three hundred pairs of mothers and neonates were included in the final analysis. Infants with IL-4 -590 C allele were found to have higher risk of elevated cbIgE (> or =0.35 IU/ml, 24.3%) (p = 0.004). After adjusting for gender, birth order, maternal age, and history of allergic disease in maternal and paternal families, odds ratios for CC and CT genotypes were 4.41 and 3.16 (95% confidence interval 0.78-22.67, and 1.66-6.13), respectively, using TT genotype as reference. The genotypes of FcepsilonRI-beta, LT-alpha, and TNF-alpha were not associated with cbIgE before or after the adjustment. Our finding suggested a significant association of cbIgE with genetic polymorphism of IL-4 -590C/T, but not with the genotypes of FcepsilonRI-beta, LT-alpha, and TNF-alpha.