A quantitative analytical method for valienone and its application in the evaluation of valienone production by a breakthrough microbial process / 中国天然药物

Valienone is a significant natural carbasugar member of the C7-cyclitol family as a valuable precursor for glycosidase inhibitor drugs. It is an intermediate of validamycin A biosynthesis pathway and exhibits minimal accumulation in the fermentation broth of the natural Streptomyces producer. A quantitative analytical method is crucial for the development of a breakthrough microbial process overcoming the consumption of the natural metabolic flux. The present study was designed to develop a pre-column derivatization high-performance liquid chromatography method for quantification of valienone and to help establish a straightforward fermentation process for valienone production by metabolically engineered Streptomyces hygroscopicus 5008. Valienone was derivatized by 2, 4-dinitrophenylhydrazine (DNPH) in 10 mmol·L HPO at 37 °C for 45 min and the derivatives were separated on Eclipse XDB-C (5 μm, 4.6 mm × 150 mm) column at 30 °C eluted with 50% acetonitrile for 18 min. The derivatives were detected by diode array detector at 380 nm and the configurations of the derivatives were determined by computational studies. The method was shown to be effective, sensitive, and reliable. Good linearity was found in the range of 5-2 000 μg·mL. The intra- and inter-day precisions were 1.1%-2.7% and 1.7%-2.2%, respectively. The absolute recovery of the spiked samples was 97.2%-102.6%. To date, this is the first reversed-phase high-performance liquid chromatography detection method for valienone in microbial culture medium. This method successfully helped evaluate the valienone production capability of the engineered Streptomyces hygroscopicus 5008 and could be promising for C7-cyclitol profiling of different engineered mutants combined with the metabonomics methods.

Social determinants of hospitalizations for ambulatory care sensitive conditions in Guarulhos, São Paulo / Los determinantes sociales de las hospitalizaciones por condiciones sensibles a la atención primaria en guarulhos, são paulo / Determinantes sociais das Internações por Condições Sensíveis à Atenção Primária em Guarulhos, São Paulo

The study goals present an overview of Hospitalizations for Ambulatory Care Sensitive Conditions (ACSC) in Guarulhos, SP, from 2008 to 2012. This is an ecological study based on secondary data obtained from the Brazilian Hospital Information System, and supported by the Praxical Theory of Intervention of Collective Health Nursing. Applied descriptive statistics for analysis. It was observed that Guarulhos shows an upward trend in hospitalizations by ACSC (20% increase), the most frequent causes of heart failure (11.8%), cerebrovascular disease (10.6%) and angina (9.7%), most frequently in the age group ≥ 65years old, for both sexes. The results are similar to other Brazilian studies, but their analysis should extrapolate the biological limits and the supply of healthcare resources, focusing on the social determinants of the health-disease process.


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El estudio tuvo como objetivo proporcionar una visión general de las Hospitalizaciones por Condiciones Sensibles a la Atención Primaria (ICSAP) en Guarulhos, SP, en el período 2008-2012. Se trata de un estudio ecológico a partir de datos secundarios obtenidos a través del Sistema de Información Hospitalaria, y apoyado por la Teoría de Intervención Práxica de la Enfermería en Salud Colectiva. Se aplicó la estadística descriptiva para el análisis. Se observó que Guarulhos muestra una tendencia al alza en las hospitalizaciones por ICSAP (aumento del 20%), las causas más frecuentes de insuficiencia cardiaca (11,8%), enfermedad cerebrovascular (10,6%) y la angina (9,7% ), con mayor frecuencia en el grupo de edad ≥ 65 años para ambos sexos. Los resultados son similares a otros estudios brasileños, pero su análisis debe extrapolar los límites biológicos y el suministro de los recursos sanitarios, centrándose en los determinantes sociales del proceso salud-enfermedad.
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Objetivo Apresentar o panorama das Internações por Condições Sensíveis à Atenção Primária (ICSAP) no município de Guarulhos, SP, no período de 2008 a 2012. Método Estudo ecológico, com dados secundários obtidos via Sistema de Informações Hospitalares, sustentado pela Teoria de Intervenção Práxica da Enfermagem em Saúde Coletiva. Empregou-se estatística descritiva para análise. Resultados Observou-se que Guarulhos apresenta trajetória crescente nas internações por ICSAP (aumento de 20%), sendo as causas mais frequentes a insuficiência cardíaca (11,8%), as doenças cerebrovasculares (10,6%) e a angina (9,7%), com maior frequência na faixa etária ≥ 65 anos, para ambos os sexos. Conclusão Os resultados encontrados assemelham-se a outros estudos brasileiros, porém sua análise deve extrapolar os limites biológicos e a oferta de recursos assistenciais, atentando para as determinações sociais do processo saúde-doença. .

Protective effect of Cardiospermum halicacabum leaf extract on glycoprotein components on STZ-induced hyperglycemic rats

OBJECTIVE@#To investigate the protective role of Cardiospermum halicacabum (C. halicacabum) leaf extract on glycoprotein metabolism in streptozotocin (STZ)-induced diabetic rats.@*METHODS@#Diabetes was induced in male albino Wistar rats by intraperitonial administration of STZ. The C. halicacabum leaf extract (CHE) was administered orally to normal and STZ-diabetic rats for 45 days. The effects of C. halicacabum leaf extract (CHE) on plasma and tissue glycoproteins (hexose, hexosamine, fucose and sialic acid) were determined.@*RESULTS@#The levels of plasma and tissues glycoproteins containing hexose, hexosamine and fucose were significantly increased in STZ-induced diabetic rats. In addition, the level of sialic acid significantly increased in plasma and liver while decreased in kidney of STZ-induced diabetic rats. After administration of CHE to diabetic rats, the metabolic alteration of glycoprotein reverted towards normal levels.@*CONCLUSIONS@#The present study indicates that the CHE possesses a protective effect on abnormal glycoprotein metabolism in addition to its antihyperglycemic activity.

Comparison of blood protein levels between diabetic and non diabetic patients with retinopathy

To compare serum protein levels between diabetic and non-diabetic patients with retinopathy. Comparative study. Ziauddin Medical University and Jinnah Postgraduate Medical Centre, Karachi, Pakistan, from 2000 to 2002. Sixty patients were selected. Among them, 21 were diabetic patients without any clinical evidence of chronic diabetic complications; 20 were diabetic patients with retinopathy and 19 were non-diabetic patients with retinopathy. Twenty-one apparently normal, age, gender and weight-matched control subjects were also inducted. All these patients were selected on clinical grounds. Blood values, fasting plasma glucose, glycosylated hemoglobin, serum fructosamine, glycosylated plasma protein, hexosamine, sialic acid and total serum proteins were determined and compared. Fasting plasma glucose was high in all diabetic patients and correlated significantly with glycosylated hemoglobin, glycosylated plasma proteins and serum fructosamine concentrations. Fasting plasma glucose, glycosylated hemoglobin, glycosylated plasma proteins, serum fructosamine, sialic acid, hexosamine and total serum protein were increased in diabetic patients with retinopathy and diabetic patients without any complications. These values were not different in diabetic patients with retinopathy and diabetic patients without chronic complications as compared with control subjects. Alpha-1 and alpha-2 globulins were significantly increased in diabetic patients with retinopathy, diabetic patients without complications and non-diabetic patients with retinopathy as compared with control subjects. Beta globulin was significantly increased in diabetic patients with retinopathy as compared with nondiabetic patients with retinopathy, diabetic patients without complication and control subjects. Gamma globulin was significantly decreased in diabetic and non-diabetic patients with retinopathy. Fasting plasma glucose, glycosylated hemoglobin, glycosylated plasma proteins, serum fructosamine, sialic acid, hexosamine and total serum protein were increased in diabetic patients with and without complications but these parameters remained within normal limits in non-diabetic patients with retinopathy. The decrease in gamma globulins may be associated with a retinopathy

Nodular goiters

The purpose of the study was to estimate the levels of amino sugars and glycosylated proteins in the blood and thyroid tissues of the patients suffering from thyroid disorders. The study was carried out at Basic Medical sciences Institute, J.P.M.C. Karachi. From 1990 to 1992. Twenty control subjects and 35 thyroid patients [Non toxic goiter = 14, Non toxic nodular goiter =12 and Toxic nodular goiter=9] were studied. T4, TBG and T4/TBG ratio, serum and tissue glucose, protein, glycosylated proteins and hexosamine with their correlation coefficient [r] were estimated. Significantly raised levels of TBG in non toxic goiter and toxic nodular goiter while T4/TBG ratio was significantly decreased in non toxic goiter and toxic nodular goiter. In non toxic goiter patients correlation coefficient analysis showed a direct relationship [serum to tissue levels] of glucose[r=0.47], glycosylated proteins[r=0.40] and hexosamine [r=0.23] while an inverse rela tionship was found in case of protein[r= -0.38]. In non toxic nodular group inverse relationship was only found in proteins [r= -0.48] estimation while direct correlation coefficient was observed in glucose [r= 0.29], glycosylated proteins [r=0.13] and in hexosamine [r=0.14]. In toxic nodular group hexosamine shows a direct correlation coefficient[r=0.73]while glucose [= -0.53], proteins [r= -0.87]and glycosylated proteins[r= -0.12] have an inverse relationship. It was concluded from correlation coefficient analysis [blood to tissue levels] that in non toxic goiter and non toxic nodular patients glucose, glycosylated protein and hexosamine showed a direct relationship while protein showed an inverse relationship

Effect of nifedipine and amlodipine on dead space wound healing in rats.

Effect of two calcium channel blockers (CCBs) nifedipine and amlodipine, was studied on normal and steroid depressed wound healing in albino rats, using the dead space wound model. The drugs enhanced normal healing as evidenced by increase in tensile strength of 10 days old granulation tissue. There was neither a significant change in the hydroxyproline level (or collagen) nor a change in the glycosaminoglycan content in granulation tissue. However, lysyloxidase level was increased significantly. The increase in tensile strength could thus be attributed to better cross-linking and maturation of collagen rather than collagen synthesis per se. The drugs were also able to overcome steroid depressed wound healing. It is likely that the prohealing effects may be related to the improved antioxidant status too, since superoxide dismutase levels were observed to be higher in the CCB- treated animals.

Establishment of an IR-HIRc cell model for screening GFAT inhibitor / 药学学报

<p><b>AIM</b>To set up an IR-HIRc cell model for screening the inhibitor of GFAT (glutamine: fructose-6-phosphate amidotransferase) , the key enzyme in the hexosamine biosynthesis pathway (HBP).</p><p><b>METHODS</b>For GFAT activity assay, the GDH method was improved by adjusting the value of pH in the reaction system and the concentrations of the reactants. The sensitivity to insulin in the cells was estimated by the measurement of insulin-induced glucose-uptake. The IR-HIRc model was set up by the stimulation of long-action insulin for 36 h. The IR-HIRc model and GDH method was used for screening GFAT inhibitor.</p><p><b>RESULTS</b>With the administration of 25 nmol x L(-1) long-action insulin in HIRe cells for 36 hours, the GFAT activity increased by 47% and the insulin-induced glucose-uptake decreased by 21%. Azaserine, a GFAT inhibitor, inhibited GFAT activity significantly in a dose-dependent manner in IR-HIRc model.</p><p><b>CONCLUSION</b>With the stimulation of 25 nmol x L(-1) long-action insulin for 36 h, excess hexosamine flux and insulin resistant in IR-HIRc cell model was set up, which can be used for screening</p>

The effect of muscovite on the quality of gastric ulcer healing / 中国中药杂志

<p><b>OBJECTIVE</b>To explore the effect of muscovite on the quality of gastric ulcer healing.</p><p><b>METHOD</b>Gastric ulcers were produced in male rats by serosal application of acetic acid. Rats were gavaged for 14 days with saline, omeprazole and muscovite starting 3 days after ulcer induction. Then the tissue and blood samples were obtained and measured.</p><p><b>RESULT</b>In the muscovite group, restored mucosa thickness increased, cystically dilated glands decreased, microvessels in connective tissue increased, the secretion of mucus, hexosamine, PGE2, EGF, bFGF were enhanced, and the express of EGFR was stronger.</p><p><b>CONCLUSION</b>Muscovite can promote the gastric ulcer healing and improve the quality of gastric ulcer healing.</p>

Effects of administration of testosterone on some biochemical correlates in seminal vesicle of Heteropneustes fossilis (Bloch) during preparatory phase: a study correlating changes in plasma testosterone level and testis activity.

In the catfish H. fossilis, administration of testosterone (0.25, 0.5, 1 and 2 micrograms/g body weight for 20 days) during mid-preparatory phase (March) increased plasma testosterone, gonadosomatic index, seminal vesicle-somatic index and concentrations of total proteins, fructose and hexosamines in seminal vesicle (SV) and testis in a dose-related manner. In the lowest dosage (0.25 microgram) group, only the hexosamine and SV protein levels were significantly high. Glucose level decreased in a dose-related manner, the decrease being not significant in the 0.25 microgram group. The results indicate that testosterone stimulates SV and testicular secretions of total proteins, hexosamines and fructose in catfish. Decrease in glucose content suggests its conversion into fructose under testosterone stimulation.

Characteristics of proteoglycans of buffalo ovarian follicular fluid during maturation of follicles.

The proteoglycans (PGs) and glycosaminoglycans (GAGs) of buffalo ovarian follicular fluid (FF) have been studied in small (2-4.9 mm), medium (5-9.9 mm) and large (> or = 10 mm) follicles. GAGs in different categories of follicles were isolated, assayed and analysed. On the basis of hexosamine analysis, glucosamine accounted for all the free GAGs in FF of small and medium follicles. No free GAG was found in large follicles. The concentration of GAGs in the form of PGs decreased significantly with follicular maturation. Qualitative analysis of GAGs from PGs showed higher galactosamine than glucosamine. The ratios of GalNH2:GluNH2 and neutral sugars were highest in small follicles followed by medium and large follicles. On the other hand, the percentage of sialic acid in GAGs was highest in large follicles followed by medium and small follicles. The fractionation of PGs by gel filtration indicated the presence of two types of PGs in buffalo ovarian FF. Difference in distribution of two types of PGs in small and large follicles was also noted.

Administration of the plasticizer di (2-ethylhexyl) phthalate alters glycoconjugate profile.

This study was undertaken to evaluate the level of glycoproteins and sialic acid in rats fed di (2-ethylhexyl)-phthalate (DEHP) in the diet for 24 weeks. Protein-bound hexose, hexosamine and sialic acid were increased in plasma and liver of rats treated with DEHP, whereas the erythrocyte membrane showed a reduction following DEHP administration. Evaluation of glycoproteins is a useful indicator of the carcinogenic process. It is suggested that profound alterations in membrane components observed in the present study may be related to the carcinogenic potential of DEHP.

Alteration in protein carbohydrate complexes in plasma of freshwater gastropod snail, Lymnaea luteola, challenged with foreign tissue implant.

Levels of protein bound hexose, hexosamine and proteins in ethanol precipitate of the body fluid and protein bound hexose and proteins in the perchloric acid filtrate of the body fluid of the snail L. luteola which received a xenoplastic implant in its cephalopedal sinus, are determined. The significant increase in protein bound hexose in the ethanol precipitate of bodyfluid in recipient snail as compared to sham operated and control snails is interesting. The results are discussed in the light of what is known about glycoproteins and their role in invertebrate immunity.

Glycation of blood proteins during pregnancy and lactation in the rat

Non-enzymatic glycation of blood proteins is a time and concentration dependent process and has been used clinically to monitor carbohydrate metabolism during human pregnancy. Since gestation in rats is of much shorter duration than in humans (3 weeks vs 9 mos) the question was raised whether similar differences in glycated proteins could be observed. Therefore, levels of glucose, glycated hemoglobin and fructosamine were measured during normal pregnancy and lactation in rats. Glucose levels during late pregnancy were significantly lower than in non pregnant and early pregnant rats. During lactation glucose levels return to normal. Glycated hemoglobin paralleled glucose decrease during late pregnancy and increased during lactation. Fructosamine followed a similar pattern. Therefore glycated hemoglobin and fructosamine appear to be reliable indicators of glucose status during gestation and lactation similar to humans and may have value as predictors of gestational diabetes mellitus once a suitable rat model is developed

Influence of serum albumin & total protein on fructosamine measurement.

To assess the effect of serum albumin and total protein on the fructosamine level 57 hypoalbuminaemic patients (serum albumin less than 30 g/1), of whom 44 were nondiabetics and 13 were diabetics, were studied. Fructosamine levels of hypoalbuminaemic diabetics was increased only marginally in comparison to healthy controls (P greater than 0.05) whereas in 122 other normalbuminaemic diabetics, the level was found to be significantly higher (P less than 0.001). In control subjects, the correlation between fructosamine and serum albumin (r = 0.69, P less than 0.001) was better than that of total protein (r = 0.42, P less than 0.01) whereas in hypoalbuminaemic patients the pattern was reversed (r = 0.51 and 0.59 respectively), indicating substantial contribution by the globulins. A working formula suggesting approximate contribution of each gram of albumin and globulin in healthy subjects was calculated. It is inferred that the use of serum fructosamine for assessment of glycaemic status could be misleading in patients with lower albumin values. Calculating serum fructosamine values from serum albumin alone in these patients is likely to be inaccurate, as it ignores the contribution of globulins which can be substantial in certain disease conditions. A gross idea regarding the glycaemic status can be obtained by comparing actual and calculated values of fructosamine from the formula.

Montaje y estandarización de la determinación de fructosamina sérica en el autoanalizador vitalab-200 / Mounting and standardization of serum fructosamine determinación in the autoanalyser vitalab 200

La cuantificación de fructosamina con fines asistenciales e investigativos se realizó a través de un procedimiento automatizado en un autoanalizador Vitalab-200. basado en el método del nitroblue tetrasolio (NBT) descrito por Johnson. La calibración del método se relizó con el patrón acuoso externo 1-deoxi 1 morfolino fructuosa, y se obtuvo una adecuada respuesta lineal que se corrobora por los resultados del análisis de regresión (r=1.00; p<0.0001). Los coeficientes de variación promedios obtenidos de los estudios de repetibilidad y reproducibilidad fueron 4.3% y 9.1% respectivamente. El estudio para el establecimiento de los rangos de referencia en sujetos normales y en pacientes diabéticos evidenció una distribución normal de valores para ambas poblaciones; el rango de valores de fructosamina obtenido para sujetos normales abarca de 0.5 a 1.3 mmol de fructosamina/L, y para pacientes diabéticos de 1,3 a 3,0 mmol de fuctosamina/L

Evaluation of diabetic control by using hemoglobin A1 and fructosamine.

Evaluation of diabetic control was performed by using fasting plasma glucose, hemoglobin A1 and fructosamine in 139 patients with diabetes mellitus, and 36 normal controls. A linear correlation of fasting plasma glucose with fructosamine and hemoglobin A1 was found. Using fasting plasma glucose alone was found to be inadequate to define good control. HbA1 and fructosamine had an acceptable sensitivity and specificity in assessment of diabetic control, although fructosamine was slightly less sensitive than HbA1. In patients with thalassemia, hemoglobin A1 levels were elevated in 18 of 19 patients. Fructosamine levels also gave misleading results since 6 to 19 patients had an elevated level and one patient had a decreased level. Patients with hypoproteinemia had a decreased fructosamine and hemoglobin A1 level compared to normal control. HbA1 and fructosamine should be cautiously interpreted in patients with thalassemia and hypoproteinemic states. Using these methods in combination with other measure such as home monitoring of blood glucose would be more precise particularly in diabetic patients with hypoproteinemia, abnormal hemoglobin and other hemolytic disorders.

Serum fructosamine and glucose tolerance in diabetics with or without microangiopathy

This study included 25 healthy non-diabetic subjects [group I], as well as 40 diabetic patients. The diabetics were 20 patients without microangiopathy [group 11] and 20 patients with diabetic microangiopathy [group 111]. Plasma glucose levels during fasting as well as 2-hours after 75 g. Glucose oral load, serum albumin, fructosamine, urea, creatinine and the 24-hours unrinary albumin were estimated. In diabetics without microangiopathy [group 11], the means of serum fructosamine, the fasting as well as the 2-hours plasma glucose levels, and the 24 hours plasma glucose levels, and the 24 hours urinary albumin were significantly higher, while the mean of serum albumin was significantly lower than the corresponding means of controls [group 1]. Indiabetics with microangiopathy [group 111], the previous findings were also present, but to a significantly greater extent only with respect to the levels of fasting plasma glucose and the urinary albumin contents. The means of the other investigated parameters were not significantly different among the two groups of diabetic patients. In addition, diabetics with or without microangiopathy who showed relatively high fasting plasma glucose levels, showed also relatively high serum fructosamine and vice versa.1 Moreover, serum fructosamine levels showed significantly positive correlation with the fasting plasma glucose levels in controls and both groups of diabetics. However, serum fructosamine levels of each group showed no significant correlation with age, body weight, serum urea, creatinine, 24 hours urinary albumin, or the presence of microangiopathic complications. Thus, in conclusion, fructosamine levels were significantly elevated in this study, this elevation was not related to the presence of diabetic microangiopathy, but most probably, it reflects the lack of glycaemic control in these patients. these findings point to the possibility of using serum fructosamine levels as marker for glycaemic control in diabetics

Dosagem de frutosamina na avaliaçäo de pacientes diabéticos: comparaçäo com o método de dosagem das proteínas glicosilados por cromatografia de afinidade / Dosage of fructosamine in the avaliation of diabetic patients: comparison with the dosage method of glycosylated proteins by affinity chromatography

Este trabalho compara o método colorimétrico automatizado (frutosamina) com o método de cromatografia de afinidade para a dosagem das proteínas séricas glicosiladas. Näo houve diferença estatística entre os valores encontrados pelos dois métodos foi em indivíduos normais. Em pacientes diabéticos do tipo I os níveis de proteína glicosilada por cromatografia de afinidade (6,1 ñ 2,2%) foram mais altos do que os observados pelo método da frutosamina (4,3 ñ 0,9 mmol/l). A correlaçäo entre os dois métodos foi 0,88.(p 0,001> O método da frutosamina apresenta as vantagens de ser mais simples e barato, e poder ser utilizado em analisadores automatizados. Já o método de cromatografia de afinidade é um melhor indicador do controle metabólico do paciente diabético