复方灵芝降糖胶囊治疗糖尿病的实验研究

探讨复方灵芝降糖胶囊（灵芝、黄芪、三七等组成）治疗糖尿病的药理作用。结果表明,复方灵芝降糖胶囊能降低正常大鼠血糖、改善糖耐量、促进血清胰岛素的释放;对正常小鼠血糖无降低作用;对链脲霉素所致的实验性糖尿病大鼠有明显降低血糖的作用,能改善糖耐量和提高血清胰岛素含量,同时能降低血桨胰高血糖素的含量,并能调节实验性糖尿病大鼠某些血糖代谢环节,如促进肝糖源、肌糖原的合成等;并能明显降低肾上腺素引起的小鼠血糖     

Is Anyone There? Use of the Telephone and Use of the Couch

Many therapists have been using the telephone for analytic sessions during the Covid 19 pandemic. This paper considers the ways in which the use of the telephone resembles the use of the couch and revisits the value of the couch in order to assess the value of the telephone. The questions raised are whether analytic therapists still find the use of the couch helpful, and if so why. This is then linked to the experience of using only the telephone. The paper considers the ways in which the two techniques increase or diminish shame and the willingness to disclose difficult material. An anonymized clinical illustration is used of a woman who began in face-to-face work with a purely practical problem, but in telephone sessions was able to acknowledge her need to understand her own mental state in order to be able to change at a deeper level. Conclusions are drawn about the positive usefulness of the telephone in contrast with the view that it is just the best that we can do in some circumstances.     

Electron beam irradiation as protection against the environmental release of recombinant molecules for biomaterials applications

In biomaterials applications there exists a need to protect against the environmental release of recombinant microorganisms and transmissible genetic material and to prevent the recovery of proprietary genetic information. Irradiation technologies have long been used to eliminate microorganisms associated with spoilage and contamination and recent studies have demonstrated that moderate doses of irradiation may be used to sterilize medically important proteins without causing adverse effects in their desirable biological properties. Recombinant Escherichia coli cells expressing organophosphate hydrolase (OPH, E.C. 3.1.8.1), an important enzyme for the detection and decontamination of neurotoxic pesticides and chemical warfare agents, were subjected to electron beam irradiation to gauge its effect on enzymatic activity, cell viability and DNA recoverability. Bacterial samples were irradiated at 2, 20 and 200 kGy using a 10 MeV electron source. Irradiation levels of 2 to 20 kGy were sufficient to eliminate viable cells without affecting OPH enzymatic activity. Biologically active DNA was recovered via PCR from all samples through the 20 kGy irradiation level. While DNA was not recovered from samples at the 200 kGy exposure level, protein activity was reduced by 19 to 78%, depending on the method of cell preparation. These results demonstrate that irradiation can be effective in preventing the release of recombinant organisms intended for use in biomaterials applications without eliminating enzymatic activity and suggests that further research may indicate specific conditions whereby DNA recovery can be eliminated while retaining sufficient enzymatic activity for targeted biomaterials applications.     

Correlation between insulin resistance and white matter lesions among non-diabetic patients with ischemic stroke

Abstract

Objective: We investigated whether a correlation exists between insulin resistance and the severity of cerebral white matter lesions among non-diabetic patients with ischemic stroke.

Methods: The subjects were 105 consecutive patients without diabetes who were hospitalized due to non-cardioembolic stroke. The insulin resistance was evaluated by a homeostasis model assessment of insulin resistance (HOMA-IR). The degrees of periventricular hyperintensity (PVH) and deep and subcortical white matter hyperintensity (DSWMH) were evaluated by the brain MRI. The HOMA-IR values ≥2·5 were indicative of the insulin resistance.

Results: The presence of PVH and DSWMH were 86·7 and 83·8%, respectively. The ratio of insulin resistance increased with higher grades of PVH and DSWMH. The HOMA-IR level in grade 3 PVH was significantly higher than those in grades 0 and 1. The HOMA-IR level in grade 3 DSWMH was significantly higher than those in grades 0–2. Multiple linear regression analysis showed that HOMA-IR was significantly associated with PVH or DSWMH.

Conclusion: It was found that insulin resistance correlated with white matter lesions among non-diabetic patients with non-cardiogenic ischemic stroke.     

Effects of Oligo(3-hydroxyalkanoates) on the Viability and Insulin Secretion of Murine Beta Cells

Biopolyesters of polyhydroxyalkanoates (PHAs), including poly-3-hydroxybutyrate (PHB), co-polyester of 3-hydroxybutyrate and 4-hydroxybutyrate (P3HB4HB), and co-polyester of 3-hydroxybutyrate and 3-hydroxyhexanoate (PHBHHx) have been well investigated for their biocompatibility. For in vivo application, it is very important that the degradation products of PHAs, especially the oligomers, are not harmful to the cells and surrounding tissues. In this study, in vitro effects of oligo(3-hydroxybutyrate) (OHB), oligo(3-hydroxybutyrate-co-4-hydroxybutyrate) (O3HB4HB) and oligo(3-hydroxybutyrate-co-3-hydroxyhexanoate) (OHBHHx) on growth and differentiation of the murine beta cell line NIT-1 were investigated. Among the three oligo-hydroxyalkanoates (Oligo-HAs), cells treated with OHBHHx displayed higher viability, as measured by CCK-8 assay. Flow cytometric analysis of NIT-1 cells indicated that Oligo-HAs had an inhibitory effect on cell apoptosis. The cytosolic Ca²⁺ transient of NIT-1 cells increased when fed with 0.04 g/l Oligo-HAs. For gap junction intercellular communication of cells, the effect of OHBHHx was the best among all materials tested. More importantly, extracellular insulin secretion was up-regulated after growing in OHBHHx for 48 h. The results demonstrated that the degradation products of PHAs, especially OHBHHx from PHBHHx, were not harmful to the beta cells. Therefore, PHBHHx warrant further study for application as a pancreatic tissue engineering material.     

Insulin Resistance and Bone Strength: Findings From the Study of Midlife in the United States

Although several studies have noted increased fracture risk in individuals with type 2 diabetes mellitus (T2DM), the pathophysiologic mechanisms underlying this association are not known. We hypothesize that insulin resistance (the key pathology in T2DM) negatively influences bone remodeling and leads to reduced bone strength. Data for this study came from 717 participants in the Biomarker Project of the Midlife in the United States Study (MIDUS II). The homeostasis model assessment of insulin resistance (HOMA‐IR) was calculated from fasting morning blood glucose and insulin levels. Projected 2D (areal) bone mineral density (BMD) was measured in the lumbar spine and left hip using dual‐energy X‐ray absorptiometry (DXA). Femoral neck axis length and width were measured from the hip DXA scans, and combined with BMD and body weight and height to create composite indices of femoral neck strength relative to load in three different failure modes: compression, bending, and impact. We used multiple linear regressions to examine the relationship between HOMA‐IR and bone strength, adjusted for age, gender, race/ethnicity, menopausal transition stage (in women), and study site. Greater HOMA‐IR was associated with lower values of all three composite indices of femoral neck strength relative to load, but was not associated with BMD in the femoral neck. Every doubling of HOMA‐IR was associated with a 0.34 to 0.40 SD decrement in the strength indices (p < 0.001). On their own, higher levels of fasting insulin (but not of glucose) were independently associated with lower bone strength. Our study confirms that greater insulin resistance is related to lower femoral neck strength relative to load. Further, we note that hyperinsulinemia, rather than hyperglycemia, underlies this relationship. Although cross‐sectional associations do not prove causality, our findings do suggest that insulin resistance and in particular, hyperinsulinemia, may negatively affect bone strength relative to load. © 2014 American Society for Bone and Mineral Research.     

The renin‐angiotensin system,blood pressure,and heart structure in patients with hereditary vitamin D–resistance rickets (HVDRR)

Vitamin D deficiency has been linked to hypertension and an increased prevalence of cardiovascular risk factors and disease. Studies in vitamin D receptor knockout (VDR KO) mice revealed an overstimulated renin‐angiotensin system (RAS) and consequent high blood pressure and cardiac hypertrophy. VDR KO mice correspond phenotypically and metabolically to humans with hereditary 1,25‐dihydroxyvitamin D–resistant rickets (HVDRR). There are no data on the cardiovascular system in human HVDRR. To better understand the effects of vitamin D on the human cardiovascular system, the RAS, blood pressure levels, and cardiac structures were examined in HVDRR patients. Seventeen patients (9 males, 8 females, aged 6 to 36 years) with hereditary HVDRR were enrolled. The control group included age‐ and gender‐matched healthy subjects. Serum calcium, phosphorous, creatinine, 25‐hydroxyvitamin D [25(OH)D],1,25‐dihydroxyvitamin D₃ [1,25(OH)₂D₃], parathyroid hormone (PTH), plasma rennin activity (PRA), aldosterone, angiotensin II (AT‐II), and angiotensin‐converting enzyme (ACE) levels were determined. Ambulatory 24‐hour blood pressure measurements and echocardiographic examinations were performed. Serum calcium, phosphorus, and alkaline phosphatase values were normal. Serum 1,25(OH)₂D₃ and PTH but not PRA and ACE levels were elevated in the HVDRR patients. AT‐II levels were higher than normal in the HVDRR patients but not significantly different from those of the controls. Aldosterone levels were normal in all HVDRR patients. No HVDRR patient had hypertension or echocardiographic pathology. These findings reveal that 6‐ to 36‐year‐old humans with HVDRR have normal renin and ACE activity, mild but nonsignificant elevation of AT‐II, normal aldosterone levels, and no hypertension or gross heart abnormalities. © 2011 American Society for Bone and Mineral Research     

Loss of Insulin Resistance after Roux-en-Y Gastric Bypass Surgery: a Time Course Study

Background: Gastric bypass has repeatedly been shown to improve and even cure type 2 diabetes by substantially improving insulin resistance. The mechanism by which it achieves this is not currently known, but some have hypothesized that there may be important humoral effects brought about by the bypass of the stomach, duodenum or proximal jejunum. A better understanding of the time course of the changes in insulin resistance after surgery might assist our understanding of potential mechanisms. Methods: Intravenous glucose tolerance tests (IVGTT) were performed in 26 severely obese patients on the morning of gastric bypass surgery and again 6 days later. In addition insulin resistance was assessed in 71 patients undergoing gastric bypass surgery by the homeostasis model assessment (HOMA) method before surgery, and again at 6 days, 3, 6, 9, and 12 months. Patients were divided into 3 groups for analysis: diabetics, impaired glucose tolerance and normal glucose tolerance. Results: All 3 groups of patients were noted to have insulin resistance prior to surgery. This was greatest in the diabetic patients, as indicated by HOMA. There was marked loss of/improvement in insulin resistance within 6 days of gastric bypass by both IVGTT and HOMA methods in all groups, which was maintained over the 12-month period. The study included 31 diabetic patients, of whom only 3 required medication following hospital discharge. Conclusion: The changes in insulin resistance seen after gastric bypass, which are responsible for the resolution or improvement of type 2 diabetes occur within 6 days of the surgery, before any appreciable weight loss has occurred. This finding has implications for our understanding of the mechanism of insulin resistance in severely obese patients and is consistent with a humoral mechanism emanating from the GI tract.     

Predictors of Nonalcoholic Steatohepatitis (NASH) in Obese Patients Undergoing Gastric Bypass

Background: Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are conditions gaining increasing recognition in hepatology as a potential cause of cirrhosis and end-stage liver disease. Obesity is one of the main risk factors. The aims of this study were to determine the frequency of NAFLD in obese patients and to identify variables that predict NASH. Methods: A prospective study was conducted of obese patients undergoing gastric bypass over a 20-month period. Assessment included liver function tests and evaluation of insulin resistance with the homeostatic model assessment (HOMA-IR). Liver biopsy was performed in all patients at the time of surgery. Clinical and biochemical variables were analyzed using a multivariate analysis to identify independent predictors of NASH. Results: 127 consecutive patients were included (62% female, 38% male, mean age 40±11 years, mean body mass index 42±6 kg/m²). Arterial hypertension was present in 52 patients (41%) and type 2 diabetes in 18 (14%). NAFLD was confirmed in 80 patients (63%), 47 (37%) had simple steatosis, and 33 (26%) had NASH. Cirrhosis was found in 2 patients corresponding to 1.6% of the total population. On multivariate analysis, AST >31 (IU/L) (OR 3.38, CI 1.17-9.8) and HOMA-IR >5.8 (OR 4.18, CI 1.39-12.49) independently predicted NASH. Conclusions: NAFLD is highly prevalent in morbidly obese patients. A high proportion of these patients exhibit NASH on histological examination. Insulin resistance represents the main predictor of NASH.     

Non-alcoholic Steatohepatitis (NASH) and Hepatocellular Carcinoma

Non-alcoholic fatty liver disease (NAFLD) is characterized by an excessive accumulation of fatty acids and triglycerides within the cytoplasm of the hepatocytes of non-alcohol users. The natural history varies according to the initial histological diagnosis. A current consideration is that cryptogenic cirrhosis may be representative of a late stage of non-alcoholic steatohepatitis (NASH), which has lost its features of necroinflammatory activity and steatosis in up to 80% of patients. Since NASH is able to progress to cirrhosis, hepatocellular carcinoma (HCC) development may be an end-stage of this disease. We report below two clinical cases of patients diagnosed with NASH who developed HCC. The relationship between NAFLD and HCC is reviewed.