ABSTRACT
Membrane transport proteins have central physiological function in maintaining cerebral homeostasis. These transporters are expressed in almost all cerebral cells in which they regulate the movement of a wide range of solutes, including endogenous substrates, xenobiotic, and therapeutic drugs. Altered activity/expression of central nervous system (CNS) transporters has been implicated in the onset and progression of multiple neurological diseases. Neurological diseases are heterogeneous diseases that involve complex pathological alterations with only a few treatment options; therefore, there is a great need for the development of novel therapeutic treatments. To that end, transporters have emerged recently to be promising therapeutic targets to halt or slow the course of neurological diseases. The objective of this review is to discuss implications of transporters in neurological diseases and summarize available evidence for targeting transporters as decent therapeutic approach in the treatment of neurological diseases.
Subject(s)
Membrane Transport Proteins/drug effects , Membrane Transport Proteins/metabolism , Molecular Targeted Therapy/methods , Nervous System Diseases/drug therapy , Nervous System Diseases/metabolism , Animals , Humans , Models, NeurologicalABSTRACT
Sternomental distance and view at laryngoscopy were documented in 523 parturients undergoing elective or emergency Caesarean section under general anaesthesia. Eighteen (3.5%) had a grade III or IV laryngoscopic view (Cormack and Lehane's classification) and were classified as potentially difficult tracheal intubations. There was a significant difference between sternomental distance in those patients with a grade III or IV laryngoscopic view compared with those with a grade I or II (13.17 (SD 1.54) cm vs 14.3 (1.49) cm; P = 0.0013). A sternomental distance of 13.5 cm or less with the head fully extended on the neck and the mouth closed provided, using discriminant analysis, the best cut-off point for predicting subsequent difficult laryngoscopy. A sternomental distance of 13.5 cm or less had a sensitivity, specificity, positive and negative predictive values of 66.7%, 71.1%, 7.6% and 98.4%, respectively. While there was no association between sternomental distance and age, weight, height or body mass index (BMI), there was a significant association between grade of laryngoscopy (III and IV) and older (P = 0.049) and heavier (P = 0.0495) mothers. The results suggest that while sternomental distance on its own may not be an adequate sole predictor of subsequent difficult laryngoscopy the measurement should be incorporated into a series of quick and simple preoperative tests.
Subject(s)
Anesthesia, General , Anesthesia, Obstetrical , Chin/anatomy & histology , Laryngoscopy , Sternum/anatomy & histology , Adolescent , Adult , Anthropometry , Cesarean Section , Female , Humans , Intubation, Intratracheal , Middle Aged , Predictive Value of Tests , Pregnancy , Risk Factors , Sensitivity and SpecificityABSTRACT
The mode of degradation of adenosine by extracts of Aspergillus terricola was suggested to be affected preliminary by adenosine deaminase to inosine and the resulting ribonucleoside was then degraded hydrolytically to give hypoxanthine and ribose. With regard to guanosine, the same extracts could initially catalyze the hydrolytic cleavage of guanosine to guanine and ribose. The resulting base was then deaminated to give xanthine by guanine deaminase. Addition of arsenate to the reaction mixture or dialyzing the extract did not affect the observed hydrolytic activity indicating the absence of phosphorylase activity or phosphorylase-phosphatase activities in the extracts.
Subject(s)
Adenosine/metabolism , Aspergillus/metabolism , Guanosine/metabolism , Guanine Deaminase/metabolism , Purine-Nucleoside Phosphorylase/metabolismABSTRACT
Cell-free extracts of nitrate-grown Aspergillus terricola could catalyze the hydrolytic cleavage of the N-glycosidic bond of adenosine, guanosine and inosine optimally at pH 4 and 50 degrees C. Incubation of the extracts at 60 degrees C for 60 minutes caused about 86%, 67% and 54% loss of activity respectively. The similarities between the pH or the temperatures profiles indicate that the hydrolytic cleavage of these purine ribonucleosides might be effected by one hydrolase. The results obtained indicate the absence of evidence for the involvement of an SH group(s) in the catalytic site. CoSO4 and CuSO4 showed a remarkable inhibiting effect on enzyme activity. The apparent Km values of the ribonucleoside hydrolase for adenosine, guanosine and inosine were calculated from Lineweaver--Burk plots and found to be 20, 22.2 and 10 x 10(-3)M respectively.
Subject(s)
Aspergillus/enzymology , Purine Nucleosides/metabolism , Ribonucleases/metabolism , Adenosine/metabolism , Cobalt/pharmacology , Copper/pharmacology , Copper Sulfate , Guanosine/metabolism , Hydrogen-Ion Concentration , Hydrolysis , Inosine/metabolism , Kinetics , Ribonucleases/antagonists & inhibitors , TemperatureABSTRACT
Cell-free extracts of nitrate-grown Aspergillus terricola catalyze the hydrolytic deamination of adenosine to inosine at maximum rate at pH 6.5 and 50 degrees C. Incubation of the extracts at 60 degrees C for 30 minutes caused about 66.7% loss in activity. Results indicated the involvement of SH groups in the catalytic site of adenosine deaminase. Frequent freezing and thawing of the enzyme preparation for three days (3 times) resulted in about 47% loss in activity. The enzyme is also inhibited by EDTA indicating that adenosine deaminase is a metaloenzyme. MgCl2 and CoSO4 had a remarkable activating effect, whereas MnCl2 showed a slight inhibitory effect on enzyme activity. The apparent Km value was calculated for adenosine and found to be 6.66 x 10(-3) M, which indicates the greater affinity of adenosine deaminase for adenosine.
