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J Sanchez-Ramos

Publications and source records attributed to J Sanchez-Ramos.

At least 37 records · Page 2Linked to original sources
PubMed1999

Oxidative DNA damage in the aging mouse brain.

The brain exhibits regional vulnerabilities to many insults, and age itself has differential effects on neuronal populations as exemplified by the age-dependent loss of dopaminergic neurons in the nigrostriatal system. We hypothesized that oxidative damage to DNA was more likely to occur in the nigrostriatal system which undergoes significant neurochemical and functional changes with age. To test this hypothesis, oxidative damage to DNA, indicated by levels of 8-hydroxy2'-deoxyguanosine (oxo8dG), was measured in pons-medulla (PM), midbrain (MB), caudate-putamen (CP), hippocampus (HP), cerebellum (CB), and cerebral cortex (CX) at 3, 18, and 34 months of age in C57/b1 mice. Steady-state levels of oxo8dG increased significantly with age in MB, CP, and CB, but not in PM, HP, or CX. Manganese superoxide dismutase (MnSOD) activity decreased with age in MB, CP, and HP, but not in PM, CB, or CX. Regional activities of Cu/Zn superoxide dismutase (Cu/Zn SOD) and glutathione peroxidase (Glut Px) did not change significantly with age. Concomitant with the regional alterations in DNA damage, there was a significant age-dependent decline in locomotor activity, motor coordination, and striatal dopamine content especially during the interval between 18 and 34 months. In conclusion, oxyradical-associated damage to DNA did not accumulate uniformly across brain regions with age and was highest in brain regions that subserve spontaneous locomotor activity and motor coordination.

Age Factors↗
PubMed1998

Medication development of ibogaine as a pharmacotherapy for drug dependence.

The potential for deriving new psychotherapeutic medications from natural sources has led to renewal interest in rain forest plants as a source of lead compounds for the development of antiaddiction medications. Ibogaine is an indole alkaloid found in the roots of Tabernanthe iboga (Apocynaceae family), a rain forest shrub that is native to equatorial Africa. Ibogaine is used by indigenous peoples in low doses to combat fatigue, hunger and in higher doses as a sacrament in religious rituals. Members of American and European addict self-help groups have claimed that ibogaine promotes long-term drug abstinence from addictive substances, including psychostimulants and cocaine. Anecdotal reports attest that a single dose of ibogaine eliminates withdrawal symptoms and reduces drug cravings for extended periods of time. The purported antiaddictive properties of ibogaine require rigorous validation in humans. We have initiated a rising tolerance study using single administration to assess the safety of ibogaine for treatment of cocaine dependency. The primary objectives of the study are to determine safety, pharmacokinetics and dose effects, and to identify relevant parameters of efficacy in cocaine-dependent patients. Pharmacokinetic and pharmacodynamic characteristics of ibogaine in humans are assessed by analyzing the concentration-time data of ibogaine and its desmethyl metabolite (noribogaine) from the Phase I trial, and by conducting in vitro experiments to elucidate the specific disposition processes involved in the metabolism of both parent drug and metabolite. The development of clinical safety studies of ibogaine in humans will help to determine whether there is a rationale for conducting efficacy trials in the future.

Animals↗
PubMed1998

Ropinirole for the treatment of early Parkinson disease: a 12-month experience. Ropinirole Study Group.

OBJECTIVE: To evaluate ropinirole hydrochloride as dopaminergic monotherapy in patients with early Parkinson disease. DESIGN: A 6-month extension of a double-blind, placebo-controlled study. SETTING: Ambulatory care at 22 different sites in the United States. PATIENTS: Patients who successfully completed the initial 6-month study could enter the 6-month extension study (ropinirole, n = 70; placebo, n = 77). INTERVENTION: Use of ropinirole or placebo therapy. MAIN OUTCOME MEASURES: The efficacy variables were the number of patients who successfully completed the 12-month study and did not require supplemental levodopa, the number of patients requiring supplemental levodopa, and the proportion of patients having an insufficient therapeutic response. RESULTS: Significantly fewer ropinirole-treated patients met criteria for insufficient therapeutic response (23 [19.8%] of 116) or required the initiation of levodopa therapy (22 [19%] of 116) compared with placebo-treated patients (60 [48%] of 125 patients for insufficient therapeutic response; 57 [45.6%] of 125 patients for additional levodopa). Significantly more ropinirole-treated patients (51 [44.0%] of 116) successfully completed the 12-month study and did not require supplemental levodopa compared with placebo-treated patients (28 [22.4%] of 125). The incidence of adverse experiences and patient withdrawals was low. CONCLUSION: Ropinirole was effective and well tolerated as monotherapy for 12 months in patients with early Parkinson disease.

Adult↗
PubMed1998

Toxicity of dieldrin for dopaminergic neurons in mesencephalic cultures.

Dieldrin can be retained for decades in lipid-rich tissue and has been measured in some postmortem PD brains. Dieldrin has been reported to deplete brain monoamines in several species and has been shown to inhibit mitochondrial respiration. To further investigate the possibility that it may be involved in the pathogenesis of parkinsonism, its toxicity for dopaminergic (DA) neurons was assessed in a mesencephalic cell culture model. Primary neuronal cultures of mesencephalic neurons were prepared from fetal rats or fetal mice, grown for 1 week and incubated with Dieldrin (0.01-100 microM) for 24 or 48 h. Toxicity for DA neurons was determined by measuring density of surviving tyrosine hydroxylase immunoreactive (TH-ir) cells. Toxicity for gamma-aminobutyric acid (GABA)-ergic neurons was determined by measuring survival of glutamate decarboxylase (GAD)-ir neurons. General, nonselective cytotoxicity was determined by counting cells visualized by phase contrast microscopy or by DAPI-stained cells with fluorescence microscopy. Dieldrin exposure for 24 h resulted in a dose-dependent decrease in survival of TH-IR cells (DA neurons) with a 50% decrease (EC50) produced by 12 microM in rat mesencephalic cultures. Dieldrin also produced a dose- and time-dependent decrease in mouse DA-ergic and GABA-ergic neurons in mouse mesencephalic cultures. GABA-ergic neurons were less sensitive to the toxin compared to DA-ergic neurons. Cellular uptake of 3H-DA was also affected by lower concentrations of Dieldrin (EC50 = 7.98 microM) than uptake of 3H-GABA (EC50 = 43 microM). Thus, Dieldrin appears to be a relatively selective DA-ergic neurotoxin in mesencephalic cultures. Dieldrin, which may be ubiquitous in the environment, is proposed as an agent which can initiate and promote dopaminergic neurodegeneration in susceptible individuals.

Animals↗
PubMed1997

Ropinirole for the treatment of early Parkinson's disease. The Ropinirole Study Group.

A prospective, randomized, placebo-controlled, double-blind, parallel-group, 6-month study assessed the efficacy and safety of ropinirole, a nonergoline D2-dopamine agonist, in patients with early Parkinson's disease (n = 241; Hoehn & Yahr stages I to III) with limited or no prior dopaminergic therapy. Patients (mean age, 62.8 years), stratified by concomitant use of selegiline, were randomized to ropinirole (n = 116) or placebo (n = 125). The starting dose of ropinirole was 0.25 mg tid with titration to at least 1.5 mg tid (maximum dose, 8 mg tid). Primary efficacy endpoint was the percentage improvement in Unified Parkinson's Disease Rating Scale (UPDRS) motor score. Ropinirole-treated patients had a significantly greater percentage improvement in UPDRS motor score than patients who received placebo (+24% vs -3%; p < 0.001). Ropinirole was well tolerated and patient withdrawals were infrequent. Most adverse experiences were related to peripheral dopaminergic activity. Ropinirole monotherapy is an effective and well-tolerated therapeutic option for treatment of early Parkinson's disease.

Aged↗
PubMed1995

Psychiatric symptoms, atypical dementia, and left visual field inattention in corticobasal ganglionic degeneration.

We longitudinally examined the neuropsychological and psychiatric characteristics of an adult male with pathologically confirmed corticobasal ganglionic degeneration (CBGD). The patient was seen on an inpatient and outpatient basis by members of the Departments of Neurology and Radiology of the University of Miami School of Medicine. Longitudinal neuropsychological testing revealed a lateralized cortical-subcortical dementia and left visual field inattention consistent with neurological and postmortem neuropathological findings of greater right hemisphere dysfunction. Symptoms of depression and obsessive-compulsive symptomatology were also documented. Our findings are consistent with prior reports indicating that CBGD is characterized by lateralized cerebral dysfunction and suggest that a detailed neuropsychological examination is a useful procedure to assist in the differential diagnosis of this movement disorder.

Aged↗
PubMed1995

Reversible parkinsonian syndrome complicating cysticercus midbrain encephalitis.

We describe a clinical picture similar to Parkinson's disease in a patient with midbrain encephalitis due to cysticercosis. The clinical, radiographic, and cerebrospinal fluid findings suggested an inflammatory reaction to a dying cyst that involved midbrain structures. The encephalopathy appeared to worsen temporarily after the institution of anticysticercus therapy. A discordance between worsening parkinsonian symptoms and improving pyramidal features was noted. Virtually a complete clinical recovery eventually ensued.

Adult↗
PubMed1995

A dual role for nitric oxide in NMDA-mediated toxicity in vivo.

Nitric oxide has been implicated in N-methyl-D-aspartate (NMDA)-mediated damage in vitro; however, its role in excitotoxic damage in vivo is not clear. In the present study we evaluated the histopathological and hemodynamic consequences of intrastriatal injections of various doses of NMDA and determined the effects of nitric oxide synthase inhibition on these changes. NMDA was injected into the striatum at doses of 50, 150, and 300 nmol with or without N omega-nitro-L-arginine methyl ester (L-NAME; 100 micrograms, locally). Three days following injections histopathological assessment was performed by morphometric analysis of the lesion area in multiple sections taken from the anterior to the posterior borders of the lesion. In animals injected with 150 and 300 nmol of NMDA (+/- L-NAME), local CBF (lCBF) was determined 30 min following injections using 14C-iodoantipyrine autoradiography. All NMDA-treated animals showed a well-demarcated lesion extending beyond the injection site. The volume of the lesion correlated significantly with the NMDA dose injected. The effects of L-NAME on lesion size were dependent on the dose of the NMDA. The lesion induced by 50 nmol of NMDA was not affected by L-NAME. With a dose of 150 nmol of NMDA, L-NAME induced a 43% increase in lesion volume. In contrast, a 38% decrease in lesion size was observed in animals treated with 300 nmol of NMDA combined with L-NAME. At a dose of 150 nmol, NMDA induced a significant elevation in lCBF, which was restricted to regions close to the injection site including the center areas of the anterior and middle striatum. The increase in lCBF observed with 150 nmol of NMDA was significantly attenuated in the NMDA + L-NAME-treated group. The lCBF changes induced by 300 nmol of NMDA were not significantly different from those in the 150-nmol group; however, the extent of the regions involved was larger. The increases in lCBF were observed in all striatal regions including the central and peripheral areas. L-NAME did not have a significant effect on the lCBF changes induced by NMDA at a dose of 300 nmol. These data suggest that in vivo the involvement of nitric oxide in NMDA toxicity depends on the NMDA dose and on the participation of hemodynamic mechanisms secondary to NMDA exposure.

Animals↗
PubMed1995

Proton MR spectroscopy of the brain in 14 patients with Parkinson disease.

PURPOSE: To determine whether the proton spectra from patients with clinically diagnosed Parkinson disease differ from the spectra of age-matched healthy subjects with respect to the major cerebral metabolite resonances as well as lactate. METHODS: Fourteen patients with Parkinson disease (38 to 81 years of age) and 13 healthy control subjects (37 to 81 years of age) were studied using image-guided, single-voxel (27-cm3 volume) proton MR spectroscopy of the occipital lobe. RESULTS: The peak area ratios of N-acetyl aspartate to creatine and N-acetyl aspartate to choline for Parkinson patients did not show a statistically significant difference from the corresponding ratios for control subjects. There was a very significant increase in the ratio of lactate to N-acetyl aspartate for patients with Parkinson disease, with the greatest increase (threefold) manifested by the subgroup (n = 4) with dementia. The difference in N-acetyl aspartate to choline between women (n = 7) with Parkinson disease and healthy women (n = 9) approached significance. No dependence of the peak ratios on age, duration of Parkinson disease, or medication (L-dopa) regimen was found. CONCLUSION: Preliminary results indicating an increase in cerebral lactate in patients with Parkinson disease support the hypothesis that Parkinson disease is a systemic disorder characterized by an impairment of oxidative energy metabolism. The larger increases for Parkinson patients with dementia may be diagnostically useful in assessing clinical course and in differentiating Parkinson disease from other causes of dementia. Additional studies are needed, though, to quantitate lactate changes and identify potential contributions from lipid resonances better.

Adult↗
PubMed1994

Gait abnormality in essential tremor.

Essential tremor (ET) has been described as a monosymptomatic disorder. In reports describing large series of patients with ET, there are rare patients who exhibit a noticeable gait disorder. However, we have observed that patients with ET and normal gait often exhibit an abnormality of tandem gait. To investigate this observation, we examined whether a gait disorder was present in 36 consecutive patients (mean age 69) with ET. We employed a tremor rating scale that scored tremor amplitude, location, and disability. In all patients, gait and tandem gait were separately evaluated. Eighteen of 36 patients (50%) exhibited tandem gait abnormalities in the presence of a normal narrow-based gait compared to 11 of 40 age-matched controls (28%) (p < 0.05). Abnormality of tandem gait was more frequently present in older ET patients and those with > 5 years of disease duration. No relationship was found between presence of tandem gait abnormality and gender, tremor severity, head involvement, or positive family history. The finding of a tandem gait abnormality in 50% of ET patients suggests that cerebellar dysfunction may be important in its pathophysiology.

Aged↗
PubMed1992

A trial of labor after cesarean section in patients with or without a prior vaginal delivery.

OBJECTIVE: To determine the outcome of labor in women with a previous cesarean section, with or without prior vaginal delivery. METHOD: Records were reviewed for 1065 women with a previous cesarean section at 'Virgen Macarena' Hospital who were attended for a subsequent labor. RESULTS: Chi-squared tests demonstrated that women with previous vaginal delivery (n = 346) had a significantly higher rate of vaginal delivery after a trial of labor (95.24%) than those without previous vaginal delivery (n = 719) (82.95%). All the ruptures of uterine scar (n = 4) were found in women without previous vaginal delivery. CONCLUSION: It appears that a cesarean section in a multiparous woman is not a determinant fact in her reproductive history and the risk of rupture of uterine scar did not appear to be present.

Cesarean Section↗
PubMed1991

Distribution and number of transferrin receptors in Parkinson's disease and in MPTP-treated mice.

Transferrin is a glycoprotein that functions primarily to deliver iron to the cell. Recent studies suggest that the transferrin receptor mediates the intracellular delivery and transport of iron bound to transferrin in the CNS. Iron-catalyzed free radical generation has been proposed as a possible cause of nigral cell death in Parkinson's disease. Our hypothesis is that abnormal iron handling by the transferrin receptor may contribute to the formation of free radical species which catalyze the lipid peroxidation of nigral cell membranes. We have assessed the number of transferrin receptors on membrane fractions prepared from the human striatum from control subjects and patients with Parkinson's disease. Equilibrium-binding studies demonstrated a reversible, saturable, and high-affinity transferrin binding site (KD = 3 nM) in human brain membranes. Regional binding assays indicate that the number of transferrin receptors in the putamen was reduced significantly in Parkinson's disease. The density of transferrin receptors was unaltered in membranes prepared from the caudate nuclei and the globus pallidus. To address the possibility that transferrin receptors are located on dopaminergic terminals, we have examined the distribution and number of transferrin receptors in the striatum of MPTP-treated mice using in vitro autoradiographic methods. In these experiments, the loss of dopaminergic terminals in the striatum was visualized by differential [3H]mazindol uptake site autoradiography. A marked reduction in the density of both transferrin receptors and [3H]mazindol binding sites was observed in the mouse striatum 7 days post-MPTP treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1991

Selective and nonselective effects of 1-methyl-4-phenylpyridinium on oxygen consumption in rat striatal and hippocampal slices.

Insights into the etiology and pathophysiology of Parkinson's disease may derive from elucidation of the neurotoxic mechanisms of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its active metabolite, 1-methyl-4-phenylpyridinium (MPP+). In previous studies, MPP+ provoked oxidation of cytochrome b and K+ leakage into the extracellular space of rat striatal slices. Magnitudes of these time-dependent responses were far greater than expected had the MPP+ effects been limited to dopaminergic terminals. To determine whether cytochromes become oxidized from K(+)-induced increases in ion transport activity or from electron transport inhibition at complex I, oxygen consumption was measured because this should be increased by the former and decreased by the latter mechanism. Low MPP+ concentrations (1 microM) decreased O2 consumption (approximately 40% in 3 h) in striatal slices. This decrease was diminished by mazindol and did not occur in hippocampal slices. High toxin concentrations (100 microM) inhibited oxygen consumption to a greater extent (approximately 60%) in striatal slices; this inhibition was still greater in hippocampal slices. These results support the hypothesis that acute effects of low ("selective") MPP+ concentrations require the presence of dopaminergic terminals to trigger a sequence of destructive metabolic events but that the metabolic consequences of MPP+ spread to neighboring cells. In contrast, high MPP+ concentrations nonselectively inhibit metabolic and ion transport activity without requiring the presence of dopaminergic terminals. These results also suggest that physiological effects of "selective" MPP+ concentrations extend to nondopaminergic cells.

1-Methyl-4-phenylpyridinium↗
PubMed1991

Visuospatial impairment in Parkinson's disease.

We explored the nature of the visuospatial deficit in Parkinson's disease (PD) and its progression as a function of disease duration. We compared the performance of 183 patients with idiopathic PD and 90 control subjects matched for age and education on six visuospatial measures. We divided patients into three groups according to the disease duration: early (1 to 4 years), middle (5 to 10 years), and advanced (greater than 10 years). Performance deteriorated in five of the six visuospatial measures, as a function of disease duration. However, the pattern of visuospatial decline depended on whether dementia was present. The results were not influenced by age or anticholinergic medication. These findings support the presence of visuospatial deficits in PD patients, with a changing pattern of impairment related to dementia and progression of the disease.

Aging↗
PubMed1990

Huntington's disease in Venezuela: 7 years of follow-up on symptomatic and asymptomatic individuals.

Persons symptomatic and at risk for Huntington's disease (HD) from a large extended family in the state of Zulia, Venezuela, have been followed prospectively for 7 years. Between 1981 and 1988, 593 people were examined, of whom 128 had symptomatic HD and 171 persons at risk had examination abnormalities that were insufficient to meet criteria for diagnosis. The remaining 294 had normal examinations. Abnormalities of saccadic eye movement and slowness of rapid alternating movements were the most common abnormalities found in at-risk individuals. Thirty persons who did not meet criteria for diagnosis at their first examination have subsequently been diagnosed with symptomatic HD. Their average age at diagnosis was 33.5 +/- 8.3 (SD) years. The likelihood of developing symptomatic HD within 3 years was 3% for those persons with normal first examinations, 23% for those with mildly abnormal first examinations, and 60% for those with highly abnormal first examinations. The rate of disease progression in early symptomatic cases were 1.4 +/- 0.1 (SEM) points per year on the Shoulson-Fahn functional capacity scale. Paternal or maternal inheritance did not appear to affect the rate of progression in this group of individuals. The data suggest that there is not a discrete age of onset but rather a prolonged period of time during which symptoms unfold.

Adolescent↗