Clinical utility of serum beta-2-microglobulin as a predictor of diabetic complications in patients with type 2 diabetes without renal impairment.

AIM: As serum beta-2-microglobulin (B2M) levels are usually elevated in patients with renal failure, they have been suggested as a surrogate marker of cardiovascular mortality for patients with chronic kidney disease. Glycation of B2M is cytotoxic and may contribute to the risk of diabetic complications in patients with diabetes. Our objective was to evaluate the relationship between B2M and diabetic complications in patients with type 2 diabetes (T2D) and normal kidney function. METHODS: A total of 366 patients with T2D and preserved renal function with no clinical evidence of cardiovascular disease were enrolled consecutively into this study. High B2M was defined as a median serum B2M level ≥ 1.8 mg/L. Subclinical atherosclerosis was defined as a carotid artery intima-media thickness (C-IMT) ≥ 0.9 mm or the presence of carotid plaque. The definition of diabetic nephropathy was based on the presence of albuminuria (≥ 30 mg/g creatinine). RESULTS: Patients with high B2M were older, and had diabetes of longer duration, higher serum creatinine, microalbuminuria, and increased vascular stiffness and C-IMT compared with patients with low B2M. B2M levels were positively correlated with C-IMT and vascular stiffness, and these associations remained constant after adjusting for age. In addition, after adjusting for age, gender, body mass index, serum creatinine, hypertension, smoking and alcohol consumption, the adjusted odds ratio (OR) for atherosclerosis was 2.01 [95% confidence interval (CI): 1.02-3.94] per 1mg/L increase in B2M. The prevalences of diabetic retinopathy and nephropathy were significantly higher with a high B2M than with a low B2M. The multiple adjusted OR for diabetic nephropathy was 2.29 (95% CI: 1.11-4.72) per 1mg/L increase of B2M. CONCLUSION: Higher serum B2M was an independent risk factor for subclinical atherosclerosis and diabetic nephropathy in patients with T2D without renal impairment.

Dual specific oral tolerance induction using interferon gamma for IgE-mediated anaphylactic food allergy and the dissociation of local skin allergy and systemic oral allergy: tolerance or desensitization?

BACKGROUND: Specific oral tolerance induction (SOTI) for IgE-mediated food allergy (IFA) can be successfully achieved using interfero gamma (classic SOTI). OBJECTIVE: In this study, a tolerable dose was introduced during tolerance induction with interferon gamma (dual SOTI), and its effectiveness was evaluated. METHODS: The study population comprised 25 IFA patients. Blood samples were taken for analysis, including complete blood count with differential counts of eosinophils, serum total IgE levels, and specific IgE for allergenic foods. Skin prick tests were conducted with the allergens. Oral food challenges were performed to diagnose IFA. Ten patients received dual SOTI, 5 received classic SOTI, 5 received SOTI without interferon gamma (original SOTI), and 5 were not treated (controls). RESULTS: Patients treated with dual SOTI and classic SOTI using interferon gamma became tolerant to the allergenic food. The tolerable dose was introduced successfully in dual SOTI. It was difficult to proceed with the same dosing protocol used for classic SOTI in cases treated with original SOTI. Following dual SOTI, the systemic reaction to oral intake subsided, but the local skin reaction to contact with the allergenic food persisted. CONCLUSIONS: Dual SOTI is an improved protocol for SOTI using interferon gamma for IFA.The local skin reaction and systemic reaction to oral intake were dissociated following dual SOTI. In cases of food allergy, tolerance appears to result from desensitization to allergens.

Dual specific oral tolerance induction using interferon gamma for IgE-mediated anaphylactic food allergy and the dissociation of local skin allergy and systemic oral allergy: tolerance or desensitization?

Background: Specific oral tolerance induction (SOTI) for IgE-mediated food allergy (IFA) can be successfully achieved using interferon gamma (classic SOTI). Objective: In this study, a tolerable dose was introduced during tolerance induction with interferon gamma (dual SOTI), and its effectiveness was evaluated. Methods: The study population comprised 25 IFA patients. Blood samples were taken for analysis, including complete blood count with differential counts of eosinophils, serum total IgE levels, and specific IgE for allergenic foods. Skin prick tests were conducted with the allergens. Oral food challenges were performed to diagnose IFA. Ten patients received dual SOTI, 5 received classic SOTI, 5 received SOTI without interferon gamma (original SOTI), and 5 were not treated (controls). Results: Patients treated with dual SOTI and classic SOTI using interferon gamma became tolerant to the allergenic food. The tolerable dose was introduced successfully in dual SOTI. It was difficult to proceed with the same dosing protocol used for classic SOTI in cases treated with original SOTI. Following dual SOTI, the systemic reaction to oral intake subsided, but the local skin reaction to contact with the allergenic food persisted. Conclusions: Dual SOTI is an improved protocol for SOTI using interferon gamma for IFA. The local skin reaction and systemic reaction to oral intake were dissociated following dual SOTI. In cases of food allergy, tolerance appears to result from desensitization to allergens (AU)

Antecedentes: La inducción de tolerancia oral específica (SOTI) para la alergia alimentaria mediada por IgE (IFA) se ha logrado empleando IFN-γ (SOTI mejorada). Objetivo: Se evaluó la eficacia de la administración de dosis tolerables de alimento junto con IFN-g durante la inducción de tolerancia (SOTI doble). Material y métodos: Se incluyeron 25 pacientes con IFA. Se analizaron muestras de sangre, realizando un hemograma completo con recuento diferencial de eosinófilos, niveles de IgE total en suero, y de IgE específica, así como pruebas cutáneas para los alimentos implicados. El diagnóstico final de IFA se realizó mediante provocación oral controlada. Diez pacientes recibieron SOTI con dosis tolerables de alimento e IFN-γ (SOTI doble), 5 recibieron SOTI usando solo IFN-γ (SOTI mejorada), 5 recibieron SOTI sin IFN-γ (SOTI convencional), y 5 no fueron tratados (grupo control).Resultados: Los pacientes tratados con SOTI doble y SOTI mejorada utilizando IFN-γ, alcanzaron la tolerancia del alimento alergénico. La dosis tolerable se alcanzó con éxito en la SOTI doble. Fue difícil el aplicar el mismo protocolo con la misma dosis en la SOTI mejorada y en los casos tratados con SOTI sin IFN-γ (SOTI convencional). Mediante SOTI doble, las reacciones sistémicas a la ingesta oral disminuyeron; sin embargo, la reacción local cutánea al contacto con el alimento alergénico permaneció invariable. Conclusiones: La SOTI doble es un protocolo mejorado para SOTI utilizando IFN-γ para el tratamiento de la IFA. La reacción local de la piel y la reacción sistémica a la ingesta oral son independientes tras la realización de la SOTI doble. La inducción de tolerancia parece ser el resultado de la desensibilización a los alérgenos (AU)

Higher levels of small dense low-density lipoprotein (LDL) are associated with cardiac autonomic neuropathy in patients with type 2 diabetes.

AIM: To investigate the relationship between small dense LDL cholesterol and cardiac autonomic neuropathy among patients with Type 2 diabetes. METHODS: A total of 175 patients who had not taken lipid-lowering agents previously were enrolled consecutively in this study. Small dense LDL cholesterol level was measured using polyacrylamide tube gel electrophoresis, which fractionates LDL cholesterol into seven components according to particle size and charge. We analysed the mean LDL cholesterol particle size and the proportion of small dense LDL cholesterol. RESULTS: The mean (± sd) patient age was 56 (± 14) years, the mean (± sd) duration of diabetes was 10.3 (± 8.3) years, the mean (± sd) proportion of small dense LDL cholesterol was 21.3 (± 17.6)% and the mean (± sd) LDL cholesterol size was 26.33 (± 0.8) nm. Men with cardiac autonomic neuropathy had a longer duration of diabetes compared with those without cardiac autonomic neuropathy. Women with cardiac autonomic neuropathy had a larger waist circumference, higher plasma triglyceride levels, smaller mean (± sd) LDL cholesterol size [26.8 (± 4.3) nm vs 26.4 (± 6.9) nm; P < 0.01] and larger mean (± sd) proportion of small dense LDL cholesterol [10.1 (± 9.9)% vs 19.1 (± 16.8)%; P < 0.01] compared with those without cardiac autonomic neuropathy. After adjusting for other confounding risk factors, the triglyceride/ HDL cholesterol ratio (odds ratio = 1.698, 95% CI: 1.07-2.69; P = 0.025) and mean LDL cholesterol size (odds ratio = 0.873, 95% CI: 0.77-0.99; P = 0.038) remained as independent risk factors for cardiac autonomic neuropathy in women. CONCLUSIONS: A more atherogenic lipid profile such as the triglyceride: HDL cholesterol ratio and a smaller mean LDL cholesterol particle size were related to the prevalence of cardiac autonomic neuropathy in women with Type 2 diabetes.

Papillary adenocarcinoma arising in a tubular duplication of the jejunum.

Alimentary tract duplications are uncommon congenital anomalies containing a normal gastrointestinal mucosa and smooth muscle layer. Intestinal duplication in the jejunum is rare, and any malignancy arising in the jejunal duplication is extremely rare. In this report, we present the first case of papillary adenocarcinoma arising in a tubular duplication of the jejunum. Coronal reformatted images from contrast-enhanced CT revealed a well-enhanced tubular mass in the distal jejunum with small bowel obstruction. There were multiple enlarged lymph nodes in the small bowel mesentery around the superior mesenteric artery. The typical macroscopic and histological findings were present.

Novel black soy peptides with antiobesity effects: activation of leptin-like signaling and AMP-activated protein kinase.

OBJECTIVE: To investigate the mechanisms underlying the antiobesity effects of a novel isoflavone-free peptide mixture (BSP) derived from black soybean. DESIGN: Long-term effects of BSP were evaluated in diet-induced obese (DIO) mice fed a high-fat (HF) diet without or with BSP (2, 5 or 10% of energy) for 13 weeks, or for 8 weeks in combination with exercise. Acute effects of BSP on food intake and body weight in rats and leptin-deficient ob/ob mice were evaluated. Cell culture models or tissue extracts were used to investigate the mechanisms underlying the antiobesity effect. MEASUREMENT: Total food intake, body weight gain, white adipose tissue (WAT) mass, plasma concentrations of leptin, adiponectin, cholesterol and triglyceride were measured. Janus kinase 2 (JAK2)-dependent signal transducers and activators of the transcription 3 (STAT3) phosphorylation and AMP-activated protein kinase (AMPK) activity were determined using Western-blot in cultured cells or tissue extracts. RESULTS: DIO mice fed an HF diet with BSP (2, 5 or 10%) for 13 weeks gained less body weight (21.4, 19.8 or 17.1 g, respectively) than the mice fed an HF diet without BSP (22.6 g) concurrent with inhibition of total food intake in a dose-dependent manner. BSP also significantly decreased food intake in rats and leptin-deficient ob/ob mice. The highest dose of BSP (10%) significantly elevated the plasma adiponectin and decreased plasma triglyceride. BSP activated JAK2-dependent STAT3 in a cell model, and elevated the level of hypothalamic phospho-STAT3 in ob/ob mice. BSP also phosphorylated AMPK and acetyl-CoA carboxylase of C2C12 myocytes in a dose-dependent manner. The antiobesity effect was augmented by low-intensity wheel-based exercise. In exercised mice, BSP significantly decreased periepididymal WAT mass and body weight gain. CONCLUSION: These results provided evidences that BSP decreased appetite and HF diet-induced body weight gain particularly in combination with exercise, through leptin-like STAT3 phosphorylation and AMPK activation.

Effects of green tea extract administration on the pharmacokinetics of clozapine in rats.

The pharmacokinetic interaction between clozapine, an atypical antipsychotic with metabolic complications, including weight gain, and green tea consumption has not been evaluated, although green tea is responsible for beneficial effects, including weight reduction, and is widely consumed in the world. Commercial green tea extract (175 mg kg(-1)) or saline was administered orally for 4 days before the oral administration of clozapine (20 mg kg(-1) ) to rats. Plasma concentrations of clozapine were measured up to 5 h after clozapine administration, and then hepatic CYP1A2 expression and activity were determined. There was no significant difference in the elimination half-life of clozapine between the green tea extract and saline groups. However, the time to reach peak concentration (T(max)) was significantly increased by green tea extract. The mean total area under the plasma concentration-time curve (AUC(0-infinity)) and maximal peak plasma concentration (C(max)) of clozapine in the green tea extract group were significantly lower than those of controls. Green tea extract induced a approximately 2-fold increase in hepatic CYP1A2 levels, while the activity increased slightly (by 10% of control). Because of this reduction in AUC and T(max) of clozapine by green tea extract pretreatment, we suggest that both the rate and amount of absorption of clozapine may be reduced by green tea extract, although the hepatic elimination phase may not be significantly altered. Therefore, the clinical implications of the effects of green tea on the bioavailability of clozapine in patients should be further evaluated.

A novel series of amphiphilic imidazolinium compounds for in vitro and in vivo gene delivery.

We have developed three catioinic amphiphiles based on the structure 1-[2-(acyloxy)ethyl]-2-alkyl(alkenyl)-3-(2-hydroxyethyl)imidazolinium chloride. Although these three compounds differ only in the structure of the hydrophobic acyl chains, they differ greatly in their ability to mediate in vivo and in vitro gene delivery. Moreover, in vitro efficiency is not predictive of in vivo efficiency. The myristoyl form is the most effective compound in vitro, and the oleoyl form is the most effective compound in vivo. The compounds readily form suspensions in aqueous media, both in the pure form and as mixtures with either cholesterol or dioleoylphosphatidylethanolamine. These suspensions can be sonicated to produce smaller particles. Particle size, electron microscopy, and the ability to capture glucose suggest that these lipids form liposomes on suspension in aqueous media. When mixed with plasmid DNA, the lipid particles appear to fuse and form larger particles. Fusion is maximal at the critical DNA:lipid ratio where extensive aggregation and precipitation are observed. Therefore, these compounds behave similarly to other cationic liposome-forming lipids upon interaction with DNA.