Carotid intima-media thickness in Chinese Type 2 diabetic subjects with or without microalbuminuria.

BACKGROUND: To examine the association of microalbuminuria (MAU) with the carotid intima-media thickness (CIMT) in Chinese Type 2 diabetic subjects. MATERIALS AND METHODS: Two hundred and thirty-nine patients (64±13 yr, 154 males) were divided into 2 groups: one with MAU (no.=119) or one without (no.=120). We recorded clinical and biochemical data as well as CIMT and ankle-brachial index (ABI). RESULTS: The patients with MAU had had diabetes mellitus (DM) longer, had higher blood pressure (BP). They also had lower estimated glomerular filtration rate (eGFR) and higher levels of circulating glucose, glycated hemoglobin, high sensitivity C-reactive protein than those without. Lower mean ABI was found in those with MAU, however, they did not have higher mean CIMT (0.72±0.15 vs 0.71±0.16 mm, p=0.525). In patients without MAU, CIMT correlated with age, DM duration, systolic BP, eGFR, albumin- to-creatinine ratio, and ABI. However, in those with MAU, CIMT correlated only with age and eGFR. Multivariate regression analysis revealed that mean CIMT correlated only with age for patients without MAU, but correlated with age and body mass index for those with MAU. Dividing the patients into 5 age groups, we found that the older the patient, the higher the mean CIMT with no group differences between those with and without MAU in both genders. However, patients with eGFR below 60 ml/min/1.73 m(2) had higher mean CIMT than those above (0.75±0.16 vs 0.69±0.14 mm, p=0.005). CONCLUSIONS: Type 2 diabetic patients with MAU were not associated with higher CIMT. Conversely, those with deterioration of renal function were more likely associated.

The experiences of non-operative treatment in patients with bacterial brain abscess.

Although treatment of brain abscess requires a combination of antimicrobials and surgical intervention for the infected foci, nonsurgical, empirical treatment is possible and efficient in selected groups of patients. A total of 31 patients were enrolled in this 22-year retrospective study. We describe our therapeutic experiences and attempt to analyze the risk factors that were predictive of therapeutic outcomes. Multiple logistic regression was used to evaluate the relationships between baseline clinical factors and therapeutic outcome during the study period. Of these 31 patients, 25 had community-acquired infections, whereas the other six had nosocomially-acquired infections. Thirteen cases (42%) had a single brain abscess and the other 18 cases (58%) had multiple brain abscesses. Furthermore, the association of bacterial meningitis and brain abscess was found in 81% (25/31) of cases. The overall case fatality rate was 48% (15/31). Significant risk factors for poor outcomes included Glasgow coma scale (GCS) at presentation, presence of septic shock and neck stiffness. In addition, each reduction of one point on the GCS increased the poor outcome rate by 28%. The findings of the study demonstrate that both a higher mortality rate (48%) and worse outcomes were found in this select group of patients. Among the significant prognostic factors, a lower mean GCS at presentation was a major determinant of poor outcome.

Atorvastatin does not affect insulin sensitivity and the adiponectin or leptin levels in hyperlipidemic Type 2 diabetes.

BACKGROUND: In addition to lipid lowering, further pleotropic effects of statins have been postulated. We aimed to study if the various pleotropic effects are due indirectly to the modulation of adipocytokines. MATERIALS AND METHODS: We studied the effect of atorvastatin on insulin sensitivity and the plasma adiponectin and leptin concentrations. Our randomized open labeled study had 29 hyperlipidemic Type 2 diabetic patients (14 females, 15 males, mean age 60.0+/-2.2 yr). They were randomized into three 12-week atorvastatin intervention types. Each day patients were given either 10 mg (no.=10), 20 mg (no.=10) or 40 mg (no.=9). Evaluations were performed before and after intervention. RESULTS: All baseline characteristics were statistically identical in the 3 groups. Drop in total cholesterol, LDL-cholesterol, and triglyceride levels were measured at the end. With 10 mg the drop was 30%, 37%, and 30%. The 20 mg group was 43%, 54%, and 34%. The 40 mg group was 42%, 51%, and 27%. Groups had no significant change of body mass index, HDLcholesterol, and glycated hemoglobin levels. Also, levels of insulin, adiponectin, leptin, homeostasis model assessment index (HOMA) and Quantitative Insulin Sensitivity Check Index (QUICKI) stayed the same. Pooled parameters of all 29 patients showed no difference in levels of insulin, adiponectin, leptin, HOMA, and QUICKI before and after treatment. CONCLUSIONS: Atorvstatin does not affect insulin sensitivity and the adiponectin or leptin levels in hyperlipidemic Type 2 diabetes.

Acidic-rich region of amyloid precursor protein induces glial cell apoptosis.

Amyloid precursor protein (APP) has several caspase cleavage sites in its C-terminal cytoplasmic domain and N-terminal extracellular domain. Caspase cleavages of APP at its cytosolic tail may result in releasing the domain and inducing cell death. During apoptosis, the N-terminal domain may also be processed at amino acids 197 and 219 by caspases leading to unmasking of an acidic-rich region (AR). In this study, AR-exposing APP was shown to inhibit cell growth after transfection into RBA-1 astrocytes and BV-2 microglial cells. The recombinant AR from residue 220 to 288 of APP (APP220-288) was produced and its biological activities were analyzed. APP220-288 induced morphological changes, cell death, and DNA fragmentation in BV-2 and RBA-1 cells. However, AR was determined to have no apparent effects in suspension cells, erythroleukemia K562 cells, and Jurkat T cells. The cytotoxicity was depending on negative charge cluster and the apoptotic activity of AR was attributed to the inhibition of cell adhesion. In BV-2 microglial cells, AR significantly stimulated Fas expression, although expressions of the pro-inflammatory cytokine genes were not detected. APP220-288 also induced nitric oxide synthase (iNOS) expression and nitric oxide (NO) production. These findings indicate that the acidic-rich domain of APP may have apoptotic activity due to inhibition of cell adhesion and induction of iNOS and Fas expressions. Moreover, unmasking the apoptosis-induced AR may activate and exacerbate glial cells which in turn lead to further progression of the death program.

Cold-induced ependymin expression in zebrafish and carp brain: implications for cold acclimation.

Cold acclimation has been suggested to be mediated by alternations in the gene expression pattern in the cold-adapted fish. To investigate the mechanism of cold acclimation in fish brain at the molecular level, relevant subsets of differentially expressed genes of interest were identified and cloned by the PCR-based subtraction suppression hybridization. Characterization of the selected cold-induced cDNA clones revealed one encoding ependymin. This gene was shown to be brain-specific. The expression of ependymin was induced by a temperature shift from 25 degrees C to 6 degrees C in Cyprinus carpio or 12 degrees C in Danio rerio. Activation of ependymin was detected 2 h after cold exposure and peaked at more than 10-fold at 12 h. This peak level remains unchanged until the temperature returns to 25 degrees C. Although the amount of soluble ependymin protein in brain was not changed by cold treatment, its level in the fibrous insoluble polymers increased 2-fold after exposure to low temperature. These findings indicate that the increase in ependymin expression is an early event that may play an important role in the cold acclimation of fish.

Characterization of Methanosarcina mazei N2M9705 isolated from an aquaculture fishpond.

A new methanogenic isolate, designated as strain N2M9705 (=OCM 668), was isolated from an aquaculture fishpond near Wang-gong, Taiwan. This strain grew on trimethylamine and methanol, but it did not catabolize H2-CO2, acetate, or formate. The cells were stained Gram-negative, nonmotile, irregular coccus 0.6-0.8 micrometer in diameter. Gas vacuoles were observed and cell aggregated to form various sizes of granules. Cells grew optimally at 32 degrees -37 degrees C with 1% NaCl. The pH range of growth was 6.2-7.4, and higher pH inhibited the cell growth. The cells grew well in minimal medium, but growth was greatly stimulated by yeast extract and peptone. A comparison of 16S rDNA sequences of this organism phylogenetically related to Methanosarcina mazei. This is the first report of methyltrophic methanogenic isolated from an aquaculture fishpond.

Regulatory factors associated with synthesis of the osmolyte glycine betaine in the halophilic methanoarchaeon Methanohalophilus portucalensis.

The halophilic methanoarchaeon Methanohalophilus portucalensis can synthesize de novo and accumulate beta-glutamine, Nepsilon-acetyl-beta-lysine, and glycine betaine (betaine) as compatible solutes (osmolytes) when grown at elevated salt concentrations. Both in vivo and in vitro betaine formation assays in this study confirmed previous nuclear magnetic resonance 13C-labelling studies showing that the de novo synthesis of betaine proceeded from glycine, sarcosine, and dimethylglycine to form betaine through threefold methylation. Exogenous sarcosine (1 mM) effectively suppressed the intracellular accumulation of betaine, and a higher level of sarcosine accumulation was accompanied by a lower level of betaine synthesis. Exogenous dimethylglycine has an effect similar to that of betaine addition, which increased the intracellular pool of betaine and suppressed the levels of Nepsilon-acetyl-beta-lysine and beta-glutamine. Both in vivo and in vitro betaine formation assays with glycine as the substrate showed only sarcosine and betaine, but no dimethylglycine. Dimethylglycine was detected only when it was added as a substrate in in vitro assays. A high level of potassium (400 mM and above) was necessary for betaine formation in vitro. Interestingly, no methylamines were detected without the addition of KCl. Also, high levels of NaCl and LiCl (800 mM) favored sarcosine accumulation, while a lower level (400 mM) favored betaine synthesis. The above observations indicate that a high sarcosine level suppressed multiple methylation while dimethylglycine was rapidly converted to betaine. Also, high levels of potassium led to greater amounts of betaine, while lower levels of potassium led to greater amounts of sarcosine. This finding suggests that the intracellular levels of both sarcosine and potassium are associated with the regulation of betaine synthesis in M. portucalensis.

Is captopril-induced improvement of insulin sensitivity mediated via endothelin?

Angiotensin-converting enzyme (ACE) inhibitors have been reported to improve insulin sensitivity during either short-term or long-term administration. Recent studies indicate that endothelin-1 (ET-1) has potent glycogenolytic effects in rat hepatocytes and may cause insulin resistance in rat adipocytes. In addition, ET may also have a role in stimulation of the hypothalamic-pituitary-adrenal axis. To test the hypothesis that part of the effect of captopril in enhancing insulin sensitivity may be mediated via ET and/or by glucocorticoids, we measured 24-h urinary excretion of ET and free cortisol before and after short-term treatment with captopril. The 24-h urinary immunoreactive endothelin (IR-ET) excretion decreased significantly (p < 0.05) from 65 +/- 4 ng at baseline to 42 +/- 3 ng after captopril treatment, whereas no significant change in the 24-h urinary free cortisol excretion was observed. Moreover, no significant change in the 24-h urinary IR-ET and free cortisol excretions was noted in the placebo-treated group. We speculate that ACE inhibitors may exert their effect on insulin sensitivity not only by blocking the renin-angiotensin and kinin systems but also by inhibiting production and/or release of ET.

Parathyroid hormone and parathyroid hormone related protein assays in the investigation of hypercalcemic patients in hospital in a Chinese population.

There are many pathological causes and potential mechanisms for hypercalcemia. We measured intact parathyroid hormone (PTH) and parathyroid hormone related protein (PTHrP) in the hypercalcemic in-patients and attempted to evaluate the roles of PTH and PTHrP in hypercalcemia due to malignancy. We performed a prospective study of 178 patients with corrected serum calcium concentrations greater than 2.74 mmol/l in a hospital over a 3-year period. We measured calcium and albumin using a Hitachi 747 autoanalyzer, and we measured PTH and PTHrP by two-site immunoradiometric assays (IRMA). Hypercalcemia was attributed to malignancy alone in 93 patients (52.3%), primary hyperparathyroidism (HPT) alone in 28 patients (15.7%), uremia with hemodialysis in 23 patients (12.9%), unknown in 16 patients (9%), primary HPT coexisting with malignancy in 7 patients (3.9%) and other rare causes (6.2%). Plasma PTHrP levels were elevated in 71/93 (76.3%) patients with hypercalcemia due to malignancy, but the elevated PTHrP percentage differed for each kind of tumor. PTHrP levels were elevated in 100% of patients with squamous carcinomas (CA) in the lung, esophagus, skin, cholangiocarcinoma of liver, and breast CA. The positive bony metastatic rate was 44.1% (41/93). There was no correlation between high PTHrP and bony metastasis. There was a good correlation between the corrected serum calcium and PTHrP levels (r = 0.476, p < 0.001), but no correlation between survival time and serum calcium level or PTHrP level. There was no significant difference in life expectancy after cancer diagnosis between the high PTHrP group and normal PTHrP group, and there was no significant difference in life expectancy after the first occurrence of hypercalcemia between the two groups. Measurement of both PTH and PTHrP levels led to a change in the initial diagnosis in 7 patients. In routine practice, measurement of serum PTH alone is not enough. This study suggests that the appropriate combination of PTH and PTHrP assays results in a more accurate diagnosis of the hypercalcemic causes. In addition, especially high PTHrP levels should be screened for malignancy. However, the prognosis in cancer patients after hypercalcemia with high PTHrP group, as compared to those with the normal PTHrP group is not significantly different.

Somatic embryogenesis and plant regeneration in callus culture derived from immature seeds and mature zygotic embryos of Dysosma pleiantha (Hance) Woodson.

Callus was induced on the wounded immature seeds and mature zygotic embryos of Dysosma pleiantha (Hance) Woodson (Berberidaceae) on a medium based on Murashige and Skoog's (1962) formula supplemented with 1 mg/l 2,4-dichlorophenoxy-acetic acid (2,4-D). Spontaneous embryoid formation occurred on the media containing low concentrations of 2,4-D (0.1-0.5 mg/l). These embryoids germinated in either MS or B5 medium containing 1 mg/l N(6)-benzyladenine and 1 mg/l gibberellic acid. The regenerated plantlets were successfully transferred to soil.