Pharmacological evaluation of Rhazya stricta root extract / Evaluación farmacológica del extracto de raíz de Rhazya stricta

The present study aimed to screen the Rhazya stricta Decne root for its antihyperglycemic and antioxidants potential through invitro assays along with phytochemical and elemental analyses. The crude extract was prepared through maceration and fractionated using solvent-solvent extraction technique. The spectroscopic studies indicated the presence of various phytochemical classes in the extract and its fractions. The antioxidant assays showed notable results along with a good concentration of phenolic and flavonoid contents. Enzyme inhibition assays demonstrated glucose-lowering effects by inhibiting the enzyme activity which could reduce post-prandial blood glucose level. The Dipeptidyl peptidase-IV (DPP-IV) inhibition assay results showed the novel DPP-IV inhibition activity of the plant extract and all fractions showed noteworthy enzyme inhibition and antihyperglycemic activity. Conclusively, the Rhazya stricta root extract displayed its antioxidant and antihyperglycemic potential due to the presence of various classes of phytochemicals and micro-nutrients.

El presente estudio tuvo como objetivo examinar la raíz de Rhazya stricta Decne por su potencial antihiperglicémico y antioxidante a través de ensayos in vitro junto con análisis fitoquímicos y elementales. El extracto crudo se preparó por maceración y se fraccionó usando una técnica de extracción solvente-solvente. Los estudios espectroscópicos indicaron la presencia de varias clases fitoquímicas en el extracto y sus fracciones. Los ensayos antioxidantes mostraron resultados notables junto con una importante concentración de contenido fenólico y flavonoide. Los ensayos de inhibición enzimática demostraron efectos reductores de la glucosa al inhibir la actividad enzimática que podría reducir el nivel de glucosa posprandial en sangre. Los resultados del ensayo de inhibición de Dipeptidyl peptidase-IV (DPP-IV) mostraron la nueva actividad de inhibición de DPP-IV del extracto de la planta y todas las fracciones mostraron una notable inhibición enzimática y actividad antihiperglicémica. En conclusión, el extracto de raíz de Rhazya stricta Decne mostró su potencial antioxidante y antihiperglicémico debido a la presencia de varias clases de fitoquímicos y micronutrientes.

Dipeptidyl Peptidase 10, a Novel Prognostic Marker in Colorectal Cancer

PURPOSE: The dipeptidyl peptidase IV (DPPIV) gene family exhibits multiple functions and is involved in the pathogenesis of various diseases. It has attracted pharmaceutical interest in the areas of metabolic disorders as well as cancer. However, clinicopathologic significance of DPPIV family in colorectal cancer is not fully understood. MATERIALS AND METHODS: The clinical relevance of DPPIV and DPP10 expression was determined by immunohistochemical staining, and by assessing its clinicopathologic correlation in 383 colorectal cancer patients with known clinical outcomes. RESULTS: DPPIV was not expressed in normal colon mucosa, but it showed luminal expression in 52 of the 383 colorectal cancers (13.5%). DPPIV expression in tumors was associated with right-sided location of the colon (p=0.010) and more advanced tumor stage (p=0.045). DPP10 was expressed in normal colonic mucosa, but its expression varied in primary colorectal cancer tissues. Loss of DPP10 expression was found in 11 colorectal cancers (CRCs) (2.9%), and multivariate analysis showed that loss of DPP10 expression was an independent factor for poor patient prognosis (p=0.008). CONCLUSION: DPP10 may play a role in disease progression of colorectal cancer and loss of DPP10 expression in primary CRC is significantly associated with poor survival outcomes.

Serum proteomics in patients with RAEB myelodysplastic syndromes / 南方医科大学学报

<p><b>OBJECTIVE</b>To screen the molecular markers for refractory anemia with excess blasts in transformation (RAEB) in myelodysplastic syndromes (MDS) by serum proteome profiling.</p><p><b>METHODS</b>The serum protein were isolated from patients with RAEB, acute myeloid leukemia or normal subjects by 2-dimensional electrophoresis (2-DE), and the electrophoresis gels were obtained to identify the differentially reacting protein spots. The replica gels of the differentially reacting proteins were analyzed to locate the matching protein spots, which were identified by peptide mass fingerprint based on matrix-assisted laser desorption/ionization time of-flight mass spectrometry (MALDI-TOF-MS) and database searching.</p><p><b>RESULTS</b>Seven differentially expressed proteins in RAEB were found by 2-DE. Of the 7 proteins, 4 were identified by MALDI-TOF-MS to have significantly differential expression in RAEB, including dipeptidyl peptidase (DPP/CD26), polymerase (DNA directed) kappa, PRO2044 and an albumin-like protein.</p><p><b>CONCLUSION</b>2-DE-based serum proteome profiling helps identify serum proteomic biomarkers related to MDS. DDP/CD26 has increased expression in the serum in RAEB subtype MDS, suggesting its possible role in advanced MDS.</p>

Association between DPP6 polymorphism and the risk of sporadic amyotrophic lateral sclerosis in Chinese patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disease characterized by the loss of motor neurons in the spinal cord, brainstem, and cerebral cortex, which results in muscle weakness, atrophy. Sporadic ALS (SALS) accounts for about 90% of ALS cases, but the etiology is largely unknown. Most of the researchers consider it to be a complex disease. There have been several genome-wide association (GWA) studies reporting several single nucleotide polymorphisms (SNPs) which are susceptible to ALS, but no data of Asians (including Chinese) yet. We investigate whether the polymorphism of rs10260404 in DPP6 gene is associated with SALS in Chinese Han origin to compare the ethnic differences between Chinese Han origin and other populations.</p><p><b>METHODS</b>The genomic DNA was extracted from the leukocytes of whole blood samples in 58 Chinese Han patients with SALS and 52 healthy controls. The asymmetric PCR was processed in the presence of an unlabeled probe that contained the rs10260404 locus. The product was genotyped on a light scanner using high resolution melting method and some were confirmed with sequencing.</p><p><b>RESULTS</b>The rs10260404 polymorphism was in Hardy-Weinberg equilibrium in patients and controls. The CC genotype and the C allele were similar in patients compared with healthy subjects and not associated with an increased risk of Chinese SALS patients (chi(2) = 0.29, OR = 1.26, 95% CI 0.55 - 2.87, P > 0.05).</p><p><b>CONCLUSIONS</b>The rs10260404 is not associated with ALS susceptibility in Chinese people with Han origin which may be due to ethnic differences. More study with large number of cases in Chinese population is really necessary.</p>

Incretin based therapies for type 2 diabetes mellitus.

The incretin effect denominates the phenomenon that oral glucose elicits a higher insulin response than intravenous glucose. Glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide are the principal hormones responsible for incretin effect. In patients with type 2 diabetes the incretin effect of these hormones is impaired. Therapeutic approaches for enhancing the incretin action include degradation resistant GLP-1 receptor agonists (incretin mimetics) and inhibitors of dipeptidyl peptidase-IV (DLP-IV) activity (incretin enhancers- gliptins). These groups of medications have similar efficacy with regards to glycaemic improvement (reduction of HbA1c between 0.5 to 1.1%) and have side-effects like nausea. The incretin mimetics are injectable agents and are more likely to reduce weight or be weight neutral when compared to the oral gliptins. Long-term studies are essential to determine the real potential and role of these newer agents in the management of type 2 diabetes.

Expressäo de CD26 em aspirados de tiroidopatias / CD26 expression in aspirates from thyroid diseases

Com o objetivo de avaliar a atividade de CD26 como marcador de neoplasias bem diferenciadas de tiróide, analisou-se 74 aspirados de tiroidopatias por meio da técnica modificada do método de Lojda. A expressäo de CD26 foi observada em carcinomas papilífero e folicular, em todas as condiçöes que apresentavam oncóccitos (tiroidite de Hashimoto, bócio com metaplasia oncocítica e neoplasia oncocítica) e em metástase de carcinoma de rim. Nossos resultados desapontam aquela expectativa de que a atividade de CD26 poderia servir de marcador de malignidade e que a reaçäo para a enzima teria valor na discriminaçäo pré-operatória entre nódulos tiroidianos benignos e malignos. Apesar de confirmar a positividade em neoplasias malignas bem diferenciadas, folicular e papilífera, o CD26 expressou-se também em todas as situaçöes que mostram oncócitos, possivelmente por se tratarem de células mais ativadas que as foliculares normais, como também em macrófagos. Já a positividade de CD26 em metástase de carcinoma de rim näo é surpreendente, tendo em vista que esta enzima pode ser encontrada, em altos níveis, na borda em escova dos túbulos proximais do rim. Mesmo assim, afastando essas condiçöes de possitividade de CD26 - por se tratar de método de execuçäo fácil e rápida -, a reaçäo pode ser utilizada, com reservas, como método auxiliar no diagnóstico diferencial entre neoplasias malignas bem diferenciadas e tiroidopatias benignas

La actividad de la enzima convertidora se encuentra incrementada en el líquido cefalorraquídeo de las ratas espontáneamente hipertensas (SHR) / The activity of converting enzyme is increased in cerebrospinal fluid in spontaneously hypertensive rats (SHR)

Se determinó la actividad de la enzima convertidora (EC,Kinasa II) del líquido cefalorraquídeo de ratas de 4 y 16 semanas de edad, espontáneamente hipertensas (SHR) y sus correspondientes controles normotensos Wistar Kyoto (WKY). Las ratas SHR adultas mostraron una mayor actividad EC ene el liquído cefalorraquídeo que las normotensas WKY (32.5+/- 5 y 19.6 +/- 1.01 nmol/hr/ml respectivamente, P<0.025. Por el contrario, no se observaron cambios significativos en la actividad enzimatica del LCR de los animales jóvenes. Nuestros resultados soportan la hipótesis de que el sistema renina-angiotensina central se encuentra sobreactivado en las ratas genéticamente hipertensas y sugieren que la medición de la actividad EC del LCR podría constituir un indice de los cambios fisiopatológicos que ocurren en el sistema renina-angiotensina central durante el desarrolllo y mantenimiento de la hipertensión

Dipeptidil carboxipeptidisa (Ec3.4.15.1) en el sistema nervioso central / Dipeptidil carboxipeptidase (Ec3.4.15.1) in the central nervous system

Presenta los resultados de un estudio realizado en los laboratorios de la Unidad de Neuroquímica Farmacológica de la Universidad de Cambridge (Inglaterra), con el fin de estudiar la actividad de la enzima convertidora de angiotensina-I (ECA) en el sistema nervioso central (SNC). En primer lugar, se estudia los resultados obtenidos en la observación de la distribución regional de la actividad de la ECA en el SNC humano y de otros mamíferos, así como su estudio, en distintas regiones cerebrales de pacientes fallecidos con los diagnósticos de enfermedad de Huntington, esquizofrenia crónica y enfermedad de Alzheimer. En segundo lugar, se presentan los resultados de estudios en los que se determinó la áctividad de la ECA en el cerebro de rata bajo diversas condiciones experimentales, tales como el tratamiento con flufenazina, hipoxia crónica y lesiones cerebrales producidas con inyecciones intracerebrales con ácido kaínico y 6 hidroxidopamina (6-OHD). Se presenta además, un esquema seguido para la purificación parcial de la actividad de la ECA a partir de tejijo cerebral humano y se describen algunas de las propiedades de la enzima así purificada. Se obtiene que la ECA cerebral pruficada, muestra alteraciones y características similares a la ECA de otros tejidos. Se encuentra con mayor acticvidad en los ganglios basales y sustancia nigra. La ECA de esta regiones es susceptible a la hipoxia crónica y al tratamiento crónico con flufenazina. La ECA se encuentra disminuida en ganglios basales y sustancia nigra de pacientes con enfermedad de Huntington y esqyizofrenia crónica de comienzo de enfermedad a edad temprana y elevada en el núcleo caudado y ciertas regions corticales de pacientes o con enfermedad de Aezheimer...