Progress in the treatment of progressive myoclonic epilepsies / 中华神经科杂志

Progressive myoclonic epilepsies (PMEs) are a group of rare genetic diseases. Common clinical manifestations include action myoclonus often with generalized tonic-clonic seizures, cognitive impairment and other focal neurological deficits. PMEs generally respond poorly to antiseizure drugs and have a poor overall prognosis. Disorders that can cause PMEs include Unverricht-Lundborg disease, Lafora disease, neuronal ceroid lipofuscinosis, myoclonic epilepsy with fragmented red fiber syndrome, sialic acidosis, dentate erythronucleus pallidus Lewy body atrophy, etc. The current treatments for PMEs include drug therapy, neuromodulatory therapy, dietary therapy, anti-inflammatory and immunomodulatory therapy, enzyme replacement therapy and gene therapy. This article reviews the currently known treatments for PMEs, and provides ideas for better research and exploration of treatments for PMEs.

Anti-diabetic effects and mechanisms of action of a Chinese herbal medicine preparation JQ-Rand in diabetic KKmice

Refined-JQ (JQ-R) is a mixture of refined extracts from(Ranunculaceae),(Leguminosae) and(Caprifoliaceae), the three major herbs of JinQi-JiangTang tablet, a traditional Chinese medicine (TCM) formula. The mechanisms by which JQ-R regulates glucose metabolism and improves insulin sensitivity were studied in type 2 diabetic KKmice and insulin-resistant L6 myotubes. To investigate the mechanisms by which JQ-R improves insulin sensitivity, a model of insulin-resistant cells induced with palmitic acid (PA) was established in L6 myotubes. Glucose uptake and expression of factors involved in insulin signaling, stress, and inflammatory pathways were detected by immunoblotting. JQ-R showed beneficial effects on glucose homeostasis and insulin resistance in a euglycemic clamp experiment and decreased fasting insulin levels in diabetic KKmice. JQ-R also improved the plasma lipid profiles. JQ-R directly increased the activity of superoxide dismutase (SOD) and decreased malondialdehyde (MDA) as well as inducible nitric oxide synthase (iNOS) levels in insulin-resistant L6 cells, and elevated the insulin-stimulated glucose uptake with upregulated phosphorylation of AKT. The phosphorylation levels of nuclear factor kappa B (NF-B p65), inhibitor of NF-B (IB), c-Jun N-terminal kinase (JNK1/2) and extracellular-signal-regulated kinases (ERK1/2) were also changed after JQ-R treatment compared with the control group. Together these findings suggest that JQ-R improved glucose and lipid metabolism in diabetic KKmice. JQ-R directly enhanced insulin-stimulated glucose uptake in insulin-resistant myotubes with improved insulin signalling and inflammatory response and oxidative stress. JQ-R could be a candidate to achieve improved glucose metabolism and insulin sensitivity in type 2 diabetes mellitus.

Determination of serum acetaminophen based on the diazo reaction and its application in the evaluation of gastric emptying / 药学学报

This study aims to establish a method to determine the serum acetaminophen concentration based on diazo reaction, and apply it in the gastric emptying evaluation. Theoretically, acetaminophen could take hydrolysis reaction in hydrochloric acid solution to produce p-aminophenol, which could then take diazo reaction resulting in a product with special absorption peak at 312 nm. Then the serum acetaminophen concentration and recovery rate were calculated according to the standard curve drawn with absorbance at 312 nm. ICR mice were given a dose of acetaminophen (500 mg x kg(-1)) by gavage and the serum acetaminophen was dynamically measured through the diazo reaction. Besides, ICR mice were subcutaneously injected with the long-acting GLP-1 analog GW002 before the gavage of acetaminophen, and serum acetaminophen concentration was measured as above to study how GW002 could influence the gastric emptying. The data showed acetaminophen ranging from 0 to 160 μg x mL(-1) could take diazo reaction with excellent linear relationship, and the regression equation was y = 0.0181 x +0.0104, R2 = 0.9997. The serum acetaminophen was also measured with good linear relationship (y = 0.0045 x + 0.0462, R = 0.9982) and the recovery rate was 97.4%-116.7%. The serum concentration of acetaminophen reached peak at about 0.5 h after gavage, and then gradually decreased. GW002 could significantly lower the serum acetaminophen concentration and make the area under the concentration-time curve (AUC) decrease by 28.4%. In conclusion, a method for the determination of serum acetaminophen based on the diazo reaction was established with good accuracy and could be used in the evaluation of gastric emptying.

Metformin ameliorates β-cell dysfunction by regulating inflammation production, ion and hormone homeostasis of pancreas in diabetic KKAy mice / 药学学报

This study is to evaluate the effects of the metformin (Met) on β cell function of diabetic KKAy mice. Female diabetic KKAy mice selected by insulin tolerance test (ITT) were divided randomly into two groups. Con group was orally administered by gavage with water, Met group with metformin hydrochloride at a dose of 0.2 g x kg(-1) for about 12 weeks. ITT and glucose tolerance tests (OGTT) were determined. Beta cell function was assessed by hyperglycemic clamp. Pancreatic biochemical indicators were tested. The changes of gene and protein expression in the pancreas and islets were also analyzed by Real-Time-PCR and immunostaining. Met significantly improved glucose intolerance and insulin resistance in KKAy mice. Fasting plasma glucose and insulin levels were also decreased. In addition, Met markedly increased glucose infusion rate (GIR) and elevated the Ist phase and maximum insulin secretion during clamp. It showed that Met decreased TG content and iNOS activities and increased Ca(2+) -Mg(2+)-ATPase activity in pancreas. Islets periphery was improved, and down-regulation of glucagon and up-regulated insulin protein expressions were found after Met treatment. Pancreatic mRNA expressions of inflammation factors including TLR4, NF-κB, JNK, IL-6 and TNF-α were down-regulated, p-NF-κB p65 protein levels also down-regulated by Met. And mRNA expressions of ion homeostasis involved in insulin secretion including SERCA2 and Kir6.2 were up-regulated by Met. Met increased SIRT5 expression level in pancreas of KKAy mice under the hyperglycemic clamp. These results indicated that chronic administration of Met regulated pancreatic inflammation generation, ion and hormone homeostasis and improved β cell function of diabetic KKAy mice.

Valibose, an alpha-glucosidase inhibitor, ameliorates the metabolic disorder of glucose and lipids and the nephropathy in streptozotocin-induced diabetic rats / 药学学报

This study is to evaluate the anti-diabetic effects of the alpha-glucosidase inhibitor valibose in a streptozotocin (STZ)-induced type 1 diabetes rat model. Diabetes was induced by a single dose of STZ (58 mg x kg(-1), ip) in SD rats, rats with elevated fasting blood glucose levels (250-450 mg x dL(-1)) were selected and divided into five groups (n = 10 in each). Another ten normal SD rats were chosen as normal group. Valibose mixed with the high sucrose diets (0.4, 1.0 and 2.5 mg 100 g(-1) diets) or acarbose (30 mg x 100 g(-1) diets) was administrated in the diabetic rats for about 5 weeks. In all groups, fasting and postprandial plasma glucose, plasma lipids, glycosylated serum protein, N-acetyl-beta-D-glucosaminidase (NAG), creatinine (Cre), blood urea nitrogen (BUN) and urine sugar levels were determined during the treatment. At the end of the experiment, the morphological alterations in kidney were evaluated by hematoxylin-eosin (HE) staining. After 3-weeks administration, valibose significantly decreased postprandial and fasting blood glucose, urine glucose, and reduced the levels of serum fructosamine. Valibose also decreased plasma triglyceride and cholesterol levels after 4 weeks treatment. These results indicated that valibose ameliorated metabolic disturbance of glucose and lipids in STZ-induced diabetic rats. In addition, valibose markedly reduced level of serum NAG and BUN, and decreased the weight index of kidney. HE staining showed reduced kidney pathological changes after valibose treatment. The findings of the present study indicate that valibose may be a novel alpha-glucosidase inhibitor for the prevention from hyperglycemia in STZ-induced type 1 diabetes rats. And valibose might have a potential role for protecting against diabetic nephropathy during hyperglycemia.

Study on the mechanism of developing hyperglycemia in monosodium glutamate induced obese mice with insulin resistance / 中华内分泌代谢杂志

The blood insulin levels of insulin resistant monosodium glutamate induced mice (IR-MSG)and hyperglycemic monosodium glutamate mice (HG-MSG) markedly increased ( P<0. 01 ), and the weight index of pancreas significantly decreased ( P<0. 01 ), accompanied with overt inflammatory infiltration in the exocrine part of pancreas. Besides, insulin and glucagon in the islets also markedly increased with irregular distribution ( P<0.01 ). Compared to IR-MSG mice, HG-MSG mice showed overt hyperglycemia and much lower blood insulin. Moreover, the weight of pancreas in HG-MSG mice markedly decreased ( P < 0.05 ), along with less insulin and more glucagon in the lessened and contracted islets, suggesting that the injury of pancreas in the HGMSG mice might be more severe, which may result in hyperglycemia.

Effect of qianjin huanglian pill on kidney in insulin resistance mice / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effect of qianjin huanglian pill on kidney in monosodium L-glutamate (MSG)-treated insulin resistance (IR) mice.</p><p><b>METHOD</b>The ameliorative effect of qianjin huanglian pill on IR in MSG mice was evaluated in comparison with rosiglitazone (Ros). The fasting serum glucose, fasting serum insulin, insulin sensitivity index, urinary albumin excretion, glomerular diameter and pathological changes of kidney were investigated in the evaluation.</p><p><b>RESULT</b>After 2 weeks of qianjin huanglian pill treatment, the urinary albumin excretion (UAE) was reduced in low-dose group (P < 0.05) as compared with the model group. After 4 weeks of qianjin huanglian pill treatment, the fasting serum glucose was reduced in high-dose group (P < 0.001 compared with the model group). ISI of mice was ameliorated in high-dose group (P < 0.05 compared with the model group). The glomerular diameter was decreased, the hyperplasia of glomerulus was ameliorated in high-dose and low-dose groups (P < 0.01 compared with model group).</p><p><b>CONCLUSION</b>In MSG mice, we found qianjin huanglian pill could increase insulin sensitivity, decrease the urinary albumin excretion, ameliorate the pathological changes of kidney due to insulin resistance.</p>