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Biomedical subjects

M Aguilar

Publications and source records attributed to M Aguilar.

104 records · Page 6Linked to original sources
PubMedDate not supplied

P glycoprotein: a new mechanism to control drug-induced nephrotoxicity.

The role of P glycoprotein (P-gp) in kidney is now being explored, and under physiological conditions, this protein is thought to be an excretory pump of cationic xenobiotics and metabolites. Functionally, two different types of P-gp have been described, but only the class I has been related to drug transport, and its overexpression confers the multidrug resistance phenotype in tumoral cells. It has been proposed that P-gp is involved in the energy-dependent transport of substrates through the cell membrane (toxic metabolites, toxins, nutrients, ions, peptides, etc.)--like a 'hydrophobic molecule vacuum cleaner'. Several physiological functions have been attributed to P-gp: defense against xenobiotic aggression and transmembrane transport of prenylcysteine methyl esters, removing these cytotoxic metabolites from cells. A variety of substrates ranging from chemotherapeutics to steroid hormones, antibiotics, and calcium channel blockers can be transported by P-gp, suggesting the possible involvement of this protein in other unknown functions. Results from our group and others have suggested that overexpression of P-gp in renal tubular and mesangial cells prevents pharmacological nephrotoxicity by cyclosporin A (CsA). On the other hand CsA, a substrate of the pump, could act as a blocker in tubular cells by competitive inhibition. One relevant aspect in kidney is the possible relationship between P-gp and protein kinase C. Several reports suggest that protein kinase C may play a role in inducing the P-gp overexpression in cells under xenobiotic pressure, through activation of the ras oncoprotein family. This could be mediated directly by angiotensin II as a ras activator. This way, the detoxicant function of P-gp against products of the ras catabolism could mediate their accumulation when the 'vacuum cleaner' function is blocked by CsA or tacrolimus, contributing to the initial development of fibroblastic activation that leads to interstitial fibrosis associated with nephrotoxicity by these immunosuppressor drugs. In conclusion, P-gp expression could be an important component of a complex detoxifying system in kidney against xenobiotics or regulating the traffic of endogenous metabolites responsible for the susceptibility of subjects to the development of nephrotoxicity against different drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Role of intrarenal endothelin 1, endothelin 3, and angiotensin II expression in chronic cyclosporin A nephrotoxicity in rats.

Endothelin 1 (Et1) is widely expressed in the kidney and is related to several functions and to pathological conditions with progression towards sclerosis. The function of endothelin 3 (Et3) at the renal level is debatable, but it could have an important regulatory function in the reabsorption of water through its action on tubular type B receptors. Angiotensin II has recently been implicated as the principal factor responsible for the progression of interstitial fibrosis induced by cyclosporin A (CsA). We investigated this relationship in vivo and analyzed the modifications induced by CsA toxicity in Sprague-Dawley rats treated with 25 mg/kg/day of CsA for 28 and 56 days. Immunohistochemical methods and molecular analysis were used to study the expression of Et1 and Et3 and immunohistochemistry alone to determine the intrarenal expression of angiotensin II. Rats treated with CsA developed chronic nephrotoxicity lesions; semiquantitative analyses of hyaline arteriolopathy revealed that the passage of time affected the extent of this lesion and led to the diminution of the total glomerular area. Immunohistochemical results showed that chronic CsA treatment induced moderate secretion of Et1 and Et3 at tubular and glomerular levels and that the local expression of angiotensin II in the treatment groups was more evident than in control animals. Besides, the mRNA levels of preproEt3 showed a dramatic increase from 28 days after CsA treatment (control group 0.07+/-0.11 vs. CsA group 0.48+/-0.11, p<0.01), while the mRNA levels of preproEt1 increased from 56 days (control group 0.15+/-0.05 vs. CsA group 0.34+/-0.09, p< 0.05). At 28 days, renal lesions correlated strongly with the mRNA levels of Et3 (r>0.50, p<0.01). However, at 56 days, the key finding was the strong correlation of the most important analytical, histological, and immunohistochemical parameters of CsA nephrotoxicity with Et1 mRNA levels (r>0.50, p<0.01). These results support the hypothesis that the clinical and morphological phenomena linked with CsA nephrotoxicity are related to hypersecretion of endothelins and local expression of angiotensin II in the outer medulla and medullary rays; Et3 and angiotensin II are the first to act, followed subsequently by Et1.

Angiotensin II↗
PubMedDate not supplied

[Trends of antidiabetic drug prescriptions in Andalucia (1986-1994)].

OBJECTIVE: Tendencies in the consumption of antidiabetic agents in Andalusia between 1986-1994 were analysed, with special emphasis on the impact of the introduction of acarbose and mechanized systems for the injection of insulin. METHODS: The information concerning consumption was obtained from the data bases of the Andalusian Health Service and the Ministry of Health which contain details of the items sold in community chemists and charged to the National Health System. Data are expressed as defined daily doses per 1000 inhabitants per day (DID). RESULTS: Insulin consumption rose from 4.67 DID in 1986 to 9.33 DID en 1994, an increase (delta) of 99.8%. All types of insulins contributed to the increase, with the mixtures rising most (delta 275%). Intermediate insulins were the most used. Prefilled syringes accounted for 25% of all insulin dispensed in 1994. Consumption of oral antidiabetic agents (OAA) rose from 12.75 DID in 1986 to 20.92 DID in 1994 (delta 64%). The most prescribed OAAs during these years were second generation sulphonylureas, representing 83% of those dispensed in 1994, followed by acarbose (11%), biguanides (3.8%), and first generation sulphonylureas (2.1%). CONCLUSIONS: There was a notable increase in the consumption of insulins and OAAs. Although the tendency in the consumption differs from that expected according to consensus agreements, qualitative changes were seen, suggesting an improvement in prescription habits. The appearance of mechanized injection systems for insulin and of acarbose have clearly modified prescription habits.

Drug Prescriptions↗
PubMedDate not supplied

[Rapid Disability Rating Scale-2 in Alzheimer's disease: NORMACODEM project data].

INTRODUCTION: The study aimed to investigate the Rapid Disability Rating Scale-2 (RDRS-2) in Alzheimer's disease (AD). Test retest reliability, internal consistency, data of discriminant validity of the scale, correlations with other functional and cognitive measures were analyzed. MATERIAL AND METHODS: 451 subjects were assessed: 254 healthy controls, 86 with cognitive impairment but no dementia (CIND) and 111 subjects diagnosed of AD. Total and subscales scores of the RDRS-2 were obtained. The total score is the sum of three subscales: activities of daily living, disability, and special problems. To establish its correlation with other functional scales and cognitive instruments, the following tools were applied: Blessed Dementia Rating Scale (BDRS), Interview for the Deterioration of Daily Living in Dementia (IDDD), Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) and the Mini-Mental State Examination (MMSE). STATISTICAL ANALYSIS: lineal multivariate regression analysis. Crossvalidation. ROC curves. Intraclass coefficient. Cronbach's alpha and Pearson's Correlation coefficient. RESULTS: RDRS-2 scores by group were the following (mean and SD): Controls (18.95; 1.64), CIND (20.61; 2.88), and AD (28.96; 9.07). Results from regression analysis 282 demonstrated absence of influence of sociocultural variables such as age and education in RDRS-2 scores. Correlations with other instruments were as following: BDRS, r=0.820; IDDD, r=0.882; ADAS-Cog, r=0.762, and MMSE, r=0.742. Intraclass coefficient was 0.86 and Cronbach's alpha was 0.91. For the RDRS-2 the best cutoff score was 21 (82.88% sensitivity and 88.8% specificity). Area under the ROC curve was 0.92. CONCLUSIONS: The Spanish adaptation of the RDRS-2 is free of sociocultural influence, and shows very adequate data on internal consistency and stability. Although not specifically designed for its use in AD it correlates highly and significantly with other functional scales as well as with the degree of cognitive impairment in AD.

Activities of Daily Living↗
PubMedDate not supplied

[Changes in the small cerebral vessels in the acquired immunodeficiency syndrome].

In the necropsy exam of the brains of 13 patients with acquired immune deficiency syndrome (AIDS) cerebrovascular lesions were seen in 5 cases, three of them having AIDS encephalopathy. Hyalinosis was noted in 3 cases, and endarteritis obliterans and fibrinoid necrosis in one case each; both of them had associated perivascular lymphocytic infiltrates. Cerebral infarction was observed in one case, but no hemorrhages were seen. The neuropathological anomalies in four children affected with the AIDS are reported too, being an extensive calcified vasculopathy and changes suggesting active AIDS encephalopathy the main findings.

AIDS Dementia Complex↗
PubMedDate not supplied

[Risk factors in cerebrovascular disease. Do transient ischemic attacks lead to changes in lifestyle?].

A minor stroke does not cause sufficient alarm in patients to change their lifestyles. 46 patients who suffered strokes in the previous 2 years were contacted by telephone, recording rehabilitation programs, medical therapy and modification of dietary habits. It was discovered that only 50% of those requiring motor rehabilitation actually received such treatment; and only one of twenty carried on speech exercises. Subsequent ischemic events were reported by 22 patients: 12 of whom had strokes, 8 ischemic myocardial attacks and two patients suffered both conditions. The majority of patients followed the prescribed medical treatment and advice badly. Of the 46 patients reviewed, 31 were hypertensive and only 16 follow recommended diets. Out of 15 smokers only, 6 gave up, and from 21 with dislypemia only 10 modified their diets. Of all patients only the most severely affected complied satisfactorily to medical treatments; a possible explanation for this would be that the contact between patients and physician (neurologist and family doctors) was discontinued immediately after the patients discharge from hospital. It is recommended therefore that steps be taken to insure better communication between neurologist, general practitioner and patient; thereby improving prognosis.

Adult↗
PubMedDate not supplied

[Validation of a test of neurological knowledge for general practitioners].

In order to evaluate the degree of neurological knowledge in a general practitioner (GP), and given the lack of a useful instrument with which to do so, we propose the drawing up of a neurological knowledge test which would give adequate psychometric guarantees. By using a broad-based sample of professionals working in Neurology (GPs, non-specialised paediatricians, and neurologists), along with sixth year medical students, and the combined work of a family doctor, a psychometry expert, a professor of neurology and two clinical neurologists, we managed to develop a multiple choice test (MCT) with 36 items that were both objective, valid, and reliable. This could be a useful means of evaluating the neurological knowledge of a GP.

Family Practice↗