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J Bustamante

Publications and source records attributed to J Bustamante.

At least 19 recordsLinked to original sources
PubMed2006

Improvement of mouse brain mitochondrial function after deprenyl treatment.

Deprenyl is a selective monoamine oxidase (MAO) B inhibitor, widely used for treatment of Parkinson's disease. The present study shows that deprenyl treatment was able to improve mitochondrial function. Fourteen month old mice were injected i.p. with deprenyl (20 mg/kg) and killed 1.5 h after the administration. Different brain subcellular fractions were isolated from control and deprenyl-treated animals to evaluate the effect of deprenyl on nitric oxide synthase (NOS) activity. Oxygen consumption, hydrogen peroxide (H(2)O(2)) production, mitochondrial membrane potential and calcium-induced permeability transition (MPT) were studied in intact mitochondria. In addition, the effect of deprenyl on respiratory complexes and MAO activities were evaluated in submitochondrial particles (SMP). Monoamine oxidase activity was found to be decreased by 55% in mitochondria from deprenyl-treated animals and as a consequence, H(2)O(2) production was significantly decreased. Deprenyl inhibited NOS activity in cytosolic fractions and SMP by 40% and 55%, respectively. In similar conditions, SMP from deprenyl-treated animals showed increased cytochrome oxidase activity. A 51% increase in the oxygen uptake in state 3 (active respiration state) was found after deprenyl treatment, but no significant changes were observed in state 4 (resting respiration state). Deprenyl treatment protected against calcium-induced depolarization and was able to inhibit calcium-induced MPT. This work provides evidence that deprenyl treatment exerts an improvement of brain mitochondrial function, through a reduction of free radical production, prevention of calcium-induced MPT and maintaining a mitochondrial transmembrane potential.

Adenosine Diphosphate↗
PubMed2006

Extensive enriched environments protect old rats from the aging dependent impairment of spatial cognition, synaptic plasticity and nitric oxide production.

In aged rodents, neuronal plasticity decreases while spatial learning and working memory (WM) deficits increase. As it is well known, rats reared in enriched environments (EE) show better cognitive performances and an increased neuronal plasticity than rats reared in standard environments (SE). We hypothesized that EE could preserve the aged animals from cognitive impairment through NO dependent mechanisms of neuronal plasticity. WM performance and plasticity were measured in 27-month-old rats from EE and SE. EE animals showed a better spatial WM performance (66% increase) than SE ones. Cytosolic NOS activity was 128 and 155% higher in EE male and female rats, respectively. Mitochondrial NOS activity and expression were also significantly higher in EE male and female rats. Mitochondrial NOS protein expression was higher in brain submitochondrial membranes from EE reared rats. Complex I activity was 70-80% increased in EE as compared to SE rats. A significant increase in the area of NADPH-d reactive neurons was observed in the parietotemporal cortex and CA1 hippocampal region of EE animals.

Aging↗
PubMed2006

Posttransplant diabetes mellitus in renal allograft recipients: A prospective multicenter study at 2 years.

The purpose of this study was to investigate the incidence and risk factors for the development of diabetes mellitus after kidney transplantation (PTDM). A total of 1783 nondiabetic renal allograft recipients transplanted from January 2000 to December 2002 were included. Diabetes was diagnosed following American Diabetes Association criteria. While 1276 patients were treated with tacrolimus (Tac), mycophenolate mofetil (MMF), and steroids, 507 patients received cyclosporine-ME (CsA), MMF, and steroids. PTDM incidence at 6, 12, and 24 months was 14.2%, 12.8%, and 13.3%, respectively. Cumulative incidence during the follow-up was 21.6%. Only 121 of the diabetic patients (47.6%) at 6 months remained diabetic at 24 months. Furthermore, 60 patients of 116 patients on insulin at 6 months (51.7%) remained on treatment at 24 months. The cumulative incidence of PTDM was similar in the two immunosuppressive treatments (19.7% on CsA-MMF vs 22.3% on Tac-MMF; P = NS). However, at 24 months, 14 of 50 diabetic patients on CsA-MMF (28%) and 74 of 161 patients on Tac-MMF (45.9%) were on insulin treatment (P < .05). By Cox regression analysis, age older than 60 years (RR 1.61; 95%CI 1.28-2.04; P < .001), body mass index (BMI) > 30 kg/m2 at transplantation (RR 1.66; 95%CI 1.27-2.16; P < .001), and immunosuppression with Tac (RR 1.30; 95%CI 1.02-1-66; P = .033) were associated with PTDM. In conclusions, the incidence of PTDM at 24 months in immunosuppressive protocols including MMF is about 22%, and it is associated with older age, increased BMI, and immnunosuppression with Tac.

Adrenal Cortex Hormones↗
PubMed2006

[Serum creatinine and creatinine clearance to estimate renal function in essential hypertension].

The shortcoming of serum creatinine (SCr) as an index of renal function is well known, patients can have significantly decreased glomerular filtration rates (GFR) with normal range SCr values, making the recognition of renal dysfunction more difficult. This study was designed to estimate renal function and the prevalence of renal dysfunction in essential hypertensive patients, comparing SCr and 4 formulas used to measure the creatinine clearance (CrCl) (the urinary CrCl formula, Cockcroft-Gault, MDRD and body surface formula) The study included 721 essential hypertensive patients, 319 men (44.2%), 402 women (55.8%), mean age 56.3 +/- 13.9 (53.7 +/- 14.4 vs 58.3 +/- 13.3). In all subjects SCr was measured and 24-h urine sample was collected to evaluate CrCl. Creatinine clereance was calculated by 4 formulas. Patients were grouped according to age (< 40, 41-65, 65-75 and > 76) and renal function was classified as normal when SCr < 1.4 in women and 1.5 mg/dl in men and CrCl (> 60 ml/m, respectively) within the above written formulas. SCr increases with age (1.01 +/- 0.36 vs 1.3 +/- 1.15) and CrCl decreases according to the 4 formulas (107.6; 92.8; 74.7 and 57.3 for the urinary SCr formula); (117.7; 87.7; 65.9 and 49.5 for the CC formula); (87.4, 74.9, 66.5 and 61 for the MDRD formula) and (97, 85.3, 71.9 and 57.3 for the body suface formula). The 4 formulas are comparable markers of renal function in the overall population. With any formula the percentage of patients with impaired renal function was much higher than indicated by the plasma creatinine alone (4% for SCr) vs 18.3-25.3% (CrCl < 60 ml/m) according to the 4 formulas. This study documents the substantial prevalence of abnormal renal function in essential hypertension. Estimation of GFR may help to facilitate the early identification of patients with renal impairment.

Adolescent↗
PubMed2005

Cystatin C as a marker of renal function in kidney transplant patients.

INTRODUCTION: Serum creatinine (sCr) is the most commonly used biochemical parameter for gauging kidney function, but, due to its limitations, it is not the ideal marker for glomerular filtration rate (GFR). Cystatin C (sCyC) appears to be an endogenous marker of GFR. AIM: To assess the use of sCyC as a marker of renal function in kidney transplant patients, we compared it with sCr and with creatinine clearance either in a 24-hour urine or calculated using the Cockroft-Gault formula. METHODS: Among 78 patients (62.8% men, 37.2% women) undergoing kidney transplantation (average age 44.87 +/- 13.37 years) we determined at 2, 5, 7, 15, and 30 days, and 6, 12 and 18 months after kidney transplantation: sCr (using the Jaffé colorimetric method), sCyC (immunonephelometry), creatinine clearance with a 24-hour urine, creatinine clearance using the Cockroft-Gault formula. RESULTS: During the first 30 days following transplantation, there was a progressive decline in sCr levels. sCyC increased up to the fifth day, coinciding with the highest doses of steroids, and then decreased. At 6, 12, and 18 months, there was a correlation between sCyC and sCr, creatinine clearance in a 24-hour urine or calculated with the Cockroft-Gault formula (R = 0.859; R = -0.713, and R = -0.684, respectively, P < .001.) CONCLUSIONS: sCyC is an endogenous marker of GFR. Its limitations relate to its being affected by the high doses of steroids in the first days following transplantation. In the 18-month posttransplant period, it correlated with creatinine clearance in a 24-hour urine or calculated by the Cockroft-Gault formula.

Adult↗
PubMed2003

Taurine-induced synaptic potentiation and the late phase of long-term potentiation are related mechanistically.

The application of taurine (2-aminoethanesulfonic acid) induces a long-lasting increase of synaptic efficacy and axon excitability (LLP-TAU) in rat hippocampal CA1 area. After taurine withdrawal, LLP-TAU lasted at least 3 h. This fact prompted us to assess whether the mechanisms involved in the maintenance of this particular potentiation were similar to those implicated in the late phase of long-term potentiation (L-LTP). In the presence of KN-62, an inhibitor of calcium/calmodulin-dependent protein kinase, taurine perfusion (10 mM, 30 min) did not affect the induction of LLP-TAU. However, LLP-TAU maintenance was completely suppressed by KT5720, an inhibitor of the cAMP-dependent protein kinase (PKA). Moreover, the late phase of LLP-TAU was blocked by inhibiting protein synthesis with anisomycin. In addition, taurine perfusion increased the phosphorylation of cAMP response element-binding protein (CREB), although did not affect cAMP levels. These features of LLP-TAU do not appear to be caused by the activation of D1/D5 dopamine receptors, as taurine also induced synaptic potentiation in the presence of SCH23390, an antagonist of this type of receptors. Finally, the late phase of both L-LTP and LLP-TAU occluded mutually. These results suggest that taurine triggers the sequence of some of the molecular events involved in the induction of L-LTP.

Animals↗
PubMed2003

Study of the activity of glutathione-peroxidase, glutathione-transferase, and glutathione-reductase in renal transplants.

The aim of this work was to study the temporare variation of oxidative stress in the plasma and erythrocytes (CR) of renal transplant patients We determined total glutathione (GST), as well as oxidized (GSSG) and reduced (GSH) fractions and the activity of glutathione peroxidase (G-px), glutathione reductase (G-red) and glutathione transferase (GSt). Determinations were performed 48 hours before transplant as well as 1 and 2 weeks after the renal transplant. The results showed a high "oxidative stress" rate, resulting from the equilibrium between the production of free radicals and the activity of antioxidants, the former being higher proportionally. Immediately after the transplant, there was an increase in oxidative stress, which resulted in an increased G-red, a marked decrease in plasma and in erythrocyte G-px (CR9 and an abrupt drop both in GST levels in plasma and in GSG (as well as in the [GSH]/[GSSG] relationship). Thereafter there was a significant improvement in the activity of antioxidant enzymes, but without normalization; the total glutathione levels and the activity of various enzymes approached the average values of the control group.

Erythrocytes↗
PubMed2003

Immunoprophylaxis with Simulect (basiliximab) in kidney transplantation: results from routine clinical practice at 18 kidney transplant units.

OBJECTIVE: The objective of this study is to assess a Simulect (basiliximab) regimen in routine clinical practice in the Spanish kidney transplantation units to evaluate efficacy and safety. METHODS: In this prospective, observational study, data on demographics, parameters of efficacy, and safety in patients who under with kidney transplantation treated with Simulect (basiliximab) were collected through an on-line collection system. RESULTS: One hundred sixty three patients at 18 kidney transplant units included 12 months follow-up. The patient mean age was 52 years (DS 13,67) including 96 (58.90%) men and 67 (41.10%) women. Cold ischemia time was 19 hours (DS 6,79). Only 2 patients presented with PRA >50%. For prophylactic immunosuppression, 67.13% of patients received triple therapy with CNI (cyclosporine 49.65% or tacrolimus 17.48%), MMF (66.43%) or AZA (10.49%), and steroids. Incidence of acute rejection (AR) at 12 months was 12.27% (1.84% steroid-resistant). In subgroup analysis, AR was 13.5% in nondiabetics and 4.5% in diabetics, including 3 steroid-resistant episodes (1.84%) in nondiabetics and none in diabetics. In relation to donor age, AR was incidence 10.3% in patients with kidneys from donors aged 50 years or younger and 10.6% when donors were older than 50 years, including 1 (1.73%) and 2 (1.93%) steroid-resistant episodes, respectively. The graft and patient survival rates at 12 months were 90% and 98%, respectively. CONCLUSIONS: Simulect (basiliximab) used in routine clinical practice provided good prophylaxis against acute rejection in several kidney transplant patient populations, similar to that observed in randomized clinical studies with excellent tolerability and safety.

Adrenal Cortex Hormones↗
PubMed2003

Liver transplantation for hepatocellular carcinoma in cirrhotic patients.

A consecutive series of 88 patients underwent transplantation for hepatocellular carcinoma with cirrhosis over a 7-year period. Liver transplantation was indicated because of the tumor in 75 cases (85.2%); tumor was an incidental finding in 13 cases (14.8%). One patient was retransplanted due to primary nonfunction. The perioperative mortality was 4.5%. Tumor recurrence was observed in seven patients (7.95%) with incidental tumor recurrence in one case. As in patients with known primary liver tumors pretransplant, a thorough follow-up is advisable to establish an early diagnosis of recurrence. The actuarial survival for nonincidental hepatocellular carcinoma at 1, 3, and 5 year was 92%, 77%, and 75%, respectively. The differences in actuarial survival between hepatitis C negative and positive hepatocellular carcinoma were not significant (log-rank test P=.27), though there was a clear improvement in results (94%, 85%, and 78% vs 90%, 71%, and 71%), at 1, 3, and 5 years meaning that HCV infection is an important prognostic factor. Although transplantation for HCC has the advantages of removing the tumor and the cirrhotic liver, it remains a controversial topic. In our experience patients showing lesions less than 5 cm or three or fewer lesions experience an equivalent survival to transplanted patients who do not have cancer.

Adult↗
PubMed2003

Isolation, characterization, and evaluation of metallothionein in renal transplant patients.

The plasma metallothionein concentration was studied in renal transplant patients. These patients are submitted to an attack of free radicals catalyzed by metals such as copper, zinc, cadmium, and others. The function of metallothionein is to bind toxic metals inhibiting the attack of free radicals and oxidative stress that patients receiving renal transplants are submitted to. This is the reason for studying this protein in this work. The metalloprotein was separated from the plasma by thermoprecipitation and molecular exclusion chromatography with Sephadex G-75 followed by anionic-ionic exchange chromatographic purification with a CINa gradient. Identification was done by SDS electrophoresis in acrylamide gel with markers and commercial protein. Finally, determinations were made by atomic absorption, silver saturation method. In this work, determinations were made in the plasma of 11 patients before and 48 h and 1 and 2 weeks after renal transplantation. The same study was carried out in parallel in a control group of 11 blood donors. The results obtained show the existence in the plasma of metallothionein, with lower concentrations in patients than in controls (19 +/- 1.2 mg vs. 12 +/- 1.2 mg). The levels were lowest in the patient group analyzed 48 h after having received the transplant (6.34 mg) and had recovered slightly one and two weeks later.

Antioxidants↗
PubMed2001

An osmotic-sensitive taurine pool is localized in rat pancreatic islet cells containing glucagon and somatostatin.

Previous reports have dealt with the hypoglycemic properties of taurine and its effects on insulin secretion by adult and fetal isolated islets. We have studied the presence and cellular distribution of taurine in rat islets, the conditions to evoke its release, and its possible modulatory action on insulin secretion. We localized taurine by techniques of double immunolabeling in most glucagon-positive cells and in some somatostatin-positive cells, whereas insulin-positive cells were not labeled with the taurine antibody. Although high-glucose stimulation did not evoke any taurine release, a hyposmotic solution (17% osmolarity reduction) induced a specific phasic release of taurine and GABA (34 and 52% increase on their basal release rate). On the other hand, taurine (10 mmol/l) application slightly reduced the second phase of insulin secretion induced by glucose stimulation. In conclusion, taurine is highly concentrated in glucagon-containing cells of the islet periphery. It is not liberated by glucose stimulation but is strongly released under hyposmotic conditions. All of these data suggest that taurine plays an osmoregulatory role in alpha-cells.

Amino Acids↗
PubMed2000

Taurine activates GABA(A) but not GABA(B) receptors in rat hippocampal CA1 area.

We investigated if taurine, an endogenous GABA analog, could mimic both hyperpolarizing and depolarizing GABA(A)-mediated responses as well as pre- and postsynaptic GABA(B)-mediated actions in the CA1 region of rat hippocampal slices. Taurine (10 mM) perfusion induced changes in membrane potential and input resistance that are compatible with GABA(A) receptor activation. Local pressure application of taurine and GABA from a double barrel pipette positioned along the dendritic shaft of pyramidal cells revealed that taurine evoked a very small change of membrane potential and resistance compared with the large changes induced by GABA in these parameters. Moreover, in the presence of GABA(A) antagonists, local application of GABA on the dendrites evoked a GABA(B)-mediated hyperpolarization while taurine did not induce any change. Taurine neither mimicked baclofen inhibitory actions on presynaptic release of glutamate and GABA as judging by the lack of taurine effect on paired-pulse facilitation ratio and slow inhibitory postsynaptic potentials, respectively. These results show that taurine mainly activates GABA(A) receptors located on the cell body, indicating therefore that if taurine has any action on the dendrites it will not be mediated by either GABA(A) or GABA(B) receptors activation.

2-Amino-5-phosphonovalerate↗
PubMed2000

Nitric oxide production and mitochondrial dysfunction during rat thymocyte apoptosis.

Production of nitric oxide (NO) by mitochondrial membranes as methemoglobin formation sensitive to N(G)-methyl-l-arginine inhibition and mitochondrial O(2) consumption in metabolic states 3 and 4 and the respiratory control (state 3/state 4) were measured at early stages of rat thymocyte apoptosis. Programmed cell death was induced by addition of methylprednisolone and etoposide to thymocyte suspensions. Increased NO production by mitochondrial membranes was observed after 30 min of methylprednisolone and etoposide addition and was accompanied by mitochondrial respiratory impairment as an early phenomenon in apoptotic thymocytes. The respiratory control in isolated mitochondria from untreated thymocytes was 4.2 +/- 0.2 and decreased to 3.1 +/- 0.2 and 1.9 +/- 0.3 after 1 h of methylprednisolone and etoposide treatment, respectively. The low mitochondrial respiratory control was accompanied by a marked decrease in GSH and cytochrome c content. Moreover, an inhibitory effect in the amount of apoptosis due to thymocyte pretreatment with N(G)-methyl-l-arginine and N(omega)-nitro-(l)-arginine (l-NNA), indicate that nitric oxide production is closely involved in the signaling of rat thymocyte apoptosis.

Animals↗
PubMed2000

[Infection after orthotopic liver transplantation: analysis of the first 120 consecutive cases].

OBJECTIVE: To report the infectious complications and presentation time of the first 120 consecutive liver transplants performed at our institution. METHODS: Prospective study of infectious complications among 120 consecutive adult patients who received orthotopic liver transplantation at Hospital de Cruces, from February 1996 to November 1998. Two patients received a renal transplant concomitantly. The same surveillance protocols were used for all patients and the criteria used to define infections were those reported by other authors. RESULTS: The group consisted of 120 patients, 95 males and 25 females. The age ranged from 20 and 66 years (mean: 54 +/- 9 years). The indications for transplantation included alcoholic cirrhosis (47%), HCV cirrhosis (20%), hepatocellular carcinoma (17.5%), fulminant hepatitis (6%), primary biliary cirrhosis (2.5%) and miscellaneous conditions (7%). Three patients required retransplantation. Acute rejection was histologically diagnosed in 38 patients (31%). None of the patients had corticosteroid-resistant rejection. Fifty-one patients (42.5%) developed 76 episodes of severe infection, which included: 48 episodes of bacterial infection among 33 patients (27.5%), tuberculosis in 7 patients (6%), 9 episodes of fungal infection among 8 patients (7%) and cytomegalovirus (CMV) infection among 8.5% of patients. No patient developed Pneumocystis carinii pneumonia. Fifteen (12.5%) patients died: six (12.5%) with active infection, and in four of them the infection was considered the cause of death. CONCLUSIONS: Infection rates due to bacteria and fungi were similar to those reported in the literature. A high rate of tuberculosis was found, which possible correlated with the high incidence of this disease in the general population. The low incidence of CMV infection was probably due to the preemptive therapy with gancyclovir. Trimethoprim-sulfamethoxazol prophylaxis against Pneumocystis carinii was highly effective.

Adult↗
PubMed2000

Taurine-induced synaptic potentiation: role of calcium and interaction with LTP.

Taurine induces a long-lasting potentiation of excitatory synaptic potentials due to the enhancement of both synaptic efficacy and axon excitability in the CA1 area of rat hippocampal slices. In this study, we characterized the role of Ca2+ in the generation of these long-lasting taurine effects. Taurine perfusion in a free-Ca2+ medium did not induce changes in either field excitatory synaptic potentials (fEPSP) slope or fiber volley (FV) amplitude. Intracellular recordings with a micropipette filled with the Ca2+ chelator BAPTA, prevented the EPSP potentiation induced by taurine in the impaled cell, whereas a long-lasting potentiation of the simultaneously recorded fEPSP was obtained. The depletion of intracellular Ca2+ stores by thapsigargin (1 microM), an inhibitor of endosomal Ca2+-ATPase, transformed the taurine-induced potentiation into a transitory process that declined to basal values after taurine withdrawal. Taurine-induced potentiation was not significantly affected by kynurenate (glutamate receptor antagonist), or nifedipine (high-voltage-activated Ca2+ channel antagonist). But, the presence of nickel (50 microM), an antagonist of low-voltage-activated Ca2+ channel, inhibited the taurine-induced potentiation, indicating that Ca2+ influx through this type of Ca2+ channels could account for the Ca2+ requirement of the taurine-induced potentiation. Occlusion experiments between tetanus-induced long-term potentiation (LTP) and taurine-induced potentiation indicate that both processes share some common mechanisms during the maintenance period.

Animals↗
PubMed2000

Free radical chemistry in biological systems.

Mitochondria are an active source of the free radical superoxide (O2-) and nitric oxide (NO), whose production accounts for about 2% and 0.5% respectively, of mitochondrial O2 uptake under physiological conditions. Superoxide is produced by the auto-oxidation of the semiquinones of ubiquinol and the NADH dehydrogenase flavin and NO by the enzymatic action of the nitric oxide synthase of the inner mitochondrial membrane (mtNOS). Nitric oxide reversibly inhibits cytochrome oxidase activity in competition with O2. The balance between NO production and its utilization results in a NO intramitochondrial steady-state concentration of 20-50 nM, which regulates mitochondrial O2 uptake and energy supply. The regulation of cellular respiration and energy production by NO and its ability to switch the pathway of cell death from apoptosis to necrosis in physiological and pathological conditions could take place primarily through the inhibition of mitochondrial ATP production. Nitric oxide reacts with O2- in a termination reaction in the mitochondrial matrix, yielding peroxynitrite (ONOO-), which is a strong oxidizing and nitrating species. This reaction accounts for approximately 85% of the rate of mitochondrial NO utilization in aerobic conditions. Mitochondrial aging by oxyradical- and peroxynitrite-induced damage would occur through selective mtDNA damage and protein inactivation, leading to dysfunctional mitochondria unable to keep membrane potential and ATP synthesis.

Aging↗