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Biomedical subjects

M Santiago

Publications and source records attributed to M Santiago.

At least 19 recordsLinked to original sources
PubMed2006

Acute perfusion of BMAA in the rat's striatum by in vivo microdialysis.

The present study is concerned with the hypothetical toxicity of beta-N-methylamino-L-alanine (BMAA), a compound that has been hypothesized to produce amyotrophic lateral sclerosis/Parkinson-dementia complex. We have used the microdialysis technique to perfused different concentrations of BMAA in the rat's striatum 24h after the implantation of a microdialysis probe (day 1). BMAA perfusion produced a dose-response increase in the extracellular output of dopamine. Forty-eight hours after implantation of the probe (day 2), we have perfused MPP+ 1 mM to check the integrity of the dopaminergic terminals present around the cannula. Only the highest concentration of BMAA studied, 50mM, produced a clear decrease in the extracellular output of dopamine after MPP+ perfusion. However, this decrease was very similar, even smaller, to that obtained in a previous study carried out by us with MPP+ 1 mM, a dose much lower than that used for BMAA. Our model to study toxicity in the striatal dopaminergic terminal did not show that acute perfusion of BMAA at high doses produces a clear damage to the dopaminergic terminals.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2006

Kinetic study of the thermoluminescence of KMgF3:LaF3 compounds employing the general one trap model.

The parameters characterising the trap centres involved in the thermoluminescence of KMgF3:LaF3 compounds have been found by deconvolving the glow curve with the General One Trap model (GOT). For the fitting procedure the Levenberg-Marquardt method has been employed. Tm-T(stop) measurements along with initial rise measurements were performed in order to estimate the number of peaks the glow curve is made up of, and the corresponding activation energies. Instead of the Runge-Kutta method, a novel algorithm has been employed to integrate the differential equation of the GOT model, which reduces the computational time nearly 30 times with respect to the former when the glow curve is recorded with a lineal heating rate profile. The strong computational time reduction makes feasible a large number of runs with different guess values. An interesting result is that the concentration of disconnected deep traps is much less than the concentration of trap centres.

Computer Simulation↗
PubMed2002

[Community-acquired pneumonia in the elderly: prognostic factors].

The incidence and mortality rates of community-acquired pneumonia are far higher in the elderly than among younger populations. However, the explanation may lie in the presence of comorbidity rather than in age itself. We performed a retrospective study of 226 patients over the age of 65 years who were admitted to our hospital with a diagnosis of community-acquired pneumonia over a period of 36 months, with the objective of identifying factors predicting mortality and to describe clinical features. The patients' mean age was 78.71 (65-96) years. One hundred forty-two were men (63%) and 84 were women (37%). Upon admission, 27.4% showed signs of altered mental state. The crude mortality rate was 20.8%. Multivariate analysis demonstrated the following independent risk factors associated with higher mortality: serum creatinine > 1.2 mg/dL (RR = 13.93; 95% CI 8.14-16.08); patient previously bedridden (RR = 5.73; 95% CI 3.41-6.79), PaO2/FiO2 < 200 (RR = 5; 95% CI 2.67-6.62) and neoplastic disease (RR = 4.08; 95% CI 1.96-5.24). The presence of chest pain was associated with a lower risk of mortality (RR = 0.11; 95% CI 0.01-0.54). Age itself was not a risk factor. We conclude that pneumonia in the elderly requires hospitalization and that it commonly presents with severe symptoms and high risk of mortality. Risk factors such as those identified in this study may help in the diagnosis and treatment of patients requiring special care.

Age Factors↗
PubMed2002

DCG-IV but not other group-II metabotropic receptor agonists induces microglial BDNF mRNA expression in the rat striatum. Correlation with neuronal injury.

We have previously described a neuroprotective action of (2S,2'R,3'R)-2-(2'3'-dicarboxycyclopropyl)glycine (DCG-IV), an agonist for group-II metabotropic receptors, on dopaminergic nerve terminals against the degeneration induced by 1-methyl-4-phenylpyridinium (MPP+). This effect was accompanied by an up-regulation of brain-derived neurotrophic factor (BDNF) mRNA expression in the rat striatum. We have now analyzed the phenotypic nature of the BDNF mRNA-expressing cells in response to intrastriatal injection of DCG-IV. Dual in situ hybridization and immunohistochemistry revealed that microglial cells but not astrocytes were responsible for this induction. Subsequent analysis demonstrated that this effect was accompanied by striking loss of striatal glutamic acid decarboxylase (GAD) mRNA and massive appearance of internucleosomal DNA fragmentation, a hallmark of apoptosis. A dose-response study demonstrated that doses of DCG-IV as low as 5 nmol was very toxic in terms GAD mRNA and apoptosis. 0.5 nmol of DCG-IV did not induce toxicity at all in terms of GAD mRNA and apoptosis. Activation of group-II metabotropic receptors in striatum with N-Acetyl-Asp-Glu (NAAG; a mGlu3 agonist) and (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (a mGlu2 and mGlu3 agonist) did not induce neither loss of GAD mRNA nor appearance of apoptosis (doses up to 20 nmol). In additional experiments, NAAG, in contrast to DCG-IV, failed to protect the striatal dopaminergic system against the degeneration induced by MPP+ as studied by microdialysis. Finally, we studied the mechanism by which DCG-IV is highly toxic. For that, selective antagonists of either metabotropic--(R,S)-alpha-methyl-4-carboxyphenylglycine and LY 341495--or ionotropic (N-methyl-D-aspartate, NMDA)--DL-2-amino-5-phosphonovaleric acid (AP-5) glutamate receptors --were co-administered with DCG-IV. Only AP-5 highly protected the striatum against the degeneration induced by DCG-IV. Since DCG-IV also activates the NMDA receptor at concentrations higher than 3 microM, it is conceivable that a intrastriatal concentration equal or higher than 3 microM after a single striatal injection of 5-20 nmol of DCG-IV. Our findings suggest that much caution must be exerted when testing the numerous neuroprotective effects ascribed to group-II metabotropic receptor activation, in particular when using DCG-IV. We conclude that the neuroprotectant capability of a given compound on a specific system does not exclude the possibility of inducing toxicity on a different one.

Animals↗
PubMed2001

Validity of a quantitative technique to study striatal dopaminergic neurodegeneration by in vivo microdialysis.

The development of a technique that allows the direct quantitative study of the damage produced by a toxin on a specific neurotransmitter system is very important. For that, we have used the microdialysis technique to validate a method to study the specific drug's toxicity on dopaminergic (DAergic) striatal terminals. We perfused different MPP(+) and 6-hydroxydopamine (6-OHDA) concentrations, with different toxicity for DAergic terminals, 24 h after the implantation of the microdialysis probe (day 1). One day later (day 2), MPP(+) was perfused through the microdialysis probe and DA extracellular output measured. We hypothesize that the amount of extracellular dopamine (DA) obtained on day 2 is directly proportional to the neurotoxic damage produced on day 1. To corroborate this hypothesis tyrosine hydroxylase (TH) immunohistochemistry was also carried out on day 2. There was a clear correlation index between the amount of DA measured after MPP(+) perfusion and the lack of TH immunoreactivity measured as the radius of the area showing decrease in TH immunoreactivity around the cannula. These results show the possibility to measure DAergic remaining terminals after a toxic drug exposure by in vivo MPP(+) perfusion. The possibility to extend this neurotoxic study to another neurotransmitter systems is suggested.

1-Methyl-4-phenylpyridinium↗
PubMed2001

Rheumatoid arthritis induced by alpha-interferon therapy.

Interferon (IFN) therapy has been used for the treatment of common diseases such as hepatitis C, myeloproliferative disorders, autoimmune diseases and various types of cancer. Given the biological properties of interferon, it is not surprising that there are a larger number of side effects due to its use. Although rheumatoid arthritis (RA) is one of the most common autoimmune diseases found in clinical practice, it does not seem to be frequently related to IFN therapy. We report a 40-year-old female patient who, after high doses of IFN-alpha therapy for malignant melanoma, developed symmetrical polyarthritis, with pain and oedema in small and large joints, associated with prolonged morning stiffness. She had positive rheumatoid factor and DR4 HLA phenotype. She was treated with deflazacort (6 mg/day), chloroquine and NSAIDs, with a partial response. In conclusion, although the development of RA after IFN therapy is a rare event, IFN may work as a 'trigger' for such complication, leading to deregulation in the immune cascade in a person genetically predisposed.

Adult↗
PubMed2001

Group II metabotropic glutamate receptor activation protects striatal dopaminergic nerve terminals against MPP+-induced neurotoxicity along with brain-derived neurotrophic factor induction.

We have studied the in vivo effect of the selective agonist for group II metabotropic glutamate receptors (2S, 2'R, 3'R)-2-(2'3'-dicarboxycyclopropyl)glycine (DCG-IV) against MPP+-induced toxicity on rat striatal dopaminergic nerve terminals by using both microdialysis and immunohistochemical techniques. Perfusion of 1 mM DCG-IV during 1 h protected dopaminergic nerve terminals against the degeneration induced by a 15-minute perfusion of 1 mM MPP+. In addition, the microglial cell population was markedly activated 24 h after DCG-IV perfusion. The astroglial cell population was only markedly activated around the microdialysis probe. This protective effect seems to be dependent on protein synthesis since 1 mM cycloheximide, an inhibitor of protein synthesis, abolished the neuroprotective effect of 1 mM DCG-IV against MPP+ toxicity. Perfusion of DCG-IV induced an upregulation of striatal brain-derived neurotrophic factor (BDNF) mRNA expressing cells which were confined precisely around the microdialysis probe. Taken together, our results suggest that the induction and release of brain-derived neurotrophic factor (BDNF) by activated glial cells induced by DCG-IV perfusion may account for its protective action against MPP+-induced dopaminergic terminal degeneration.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2000

Neurotoxic relationship between dopamine and iron in the striatal dopaminergic nerve terminals.

The neurotoxic effect of dopamine (DA) and iron(III) on DAergic terminals in striatum has been studied by intracerebral microdialysis technique. Twenty-four hours after surgery (day 1), DA and/or iron(III) with and without DA reuptake inhibitor, nomifensine, were perfused for 1 h. Forty-eight hours after surgery (day 2), MPP(+) 1 mM was perfused for 15 min and the output of DA was measured, its amount being directly proportional to the remaining striatal DAergic terminals, supported by tyrosine hydroxylase immunohistochemistry technique. Perfusion of exogenous DA, as well as iron(III) 10 and 100 microM, did not produce any neurotoxic effect. However, perfusion of iron(III) (333 and 1000 microM) produced a concentration-dependent toxic effect. Co-perfusion of iron(III) at non-toxic concentration (100 microM) with DA (15 microM) produced a toxic effect. Elevation of the endogenous extracellular levels of DA by inhibiting its uptake with nomifensine increased the neurotoxic effect of iron(III) in a dose-dependent manner. The use of tetrodotoxin after elevation of DA with nomifensine partially prevented the neurotoxic effect of its co-perfusion with iron(III) (100 microM). These results suggest that DAergic system could be synergistically damaged by DA and iron(III). Thus, alterations in the clearance of DA from extracellular space along with an increase of iron may have significant consequences for DAergic system toxicity.

1-Methyl-4-phenylpyridinium↗
PubMed2000

Hypertrichosis in systemic lupus erythematosus (SLE).

We describe a 14-year-old female with systemic lupus erythematosus (SLE) involving the skin, joints and central nervous system who developed hypertrichosis of the upper eyelashes. This clinical finding has been observed in immunocompromised patients with acquired immune deficiency syndrome (AIDS), malnutrition, cancer or kala-azar. Although the pathogenic mechanism for this type of hypertrichosis is unknown, we believe the immunological defects seen in SLE may be responsible for such manifestation in our patient.

Adolescent↗
PubMed2000

Decreased messenger RNA expression of key markers of the nigrostriatal dopaminergic system following vitamin E deficiency in the rat.

We have evaluated the effect of a vitamin E-deficient diet on the rat nigrostriatal dopaminergic system. After 15 days of deficient diet, the amount and activity of striatal and nigral tyrosine hydroxylase increased, which contrasted with a decreased messenger RNA expression for tyrosine hydroxylase and the dopamine transporter in the ventral mesencephalon. When we prolonged the deficiency of vitamin E for 30 days, dopamine levels did not differ in both areas. In contrast, messenger RNA levels for tyrosine hydroxylase and the dopamine transporter were markedly reduced in 30-day deficient rats. In addition, the number of oxidatively modified proteins significantly increased in the striatal and nigral areas studied. Overall, we propose that these changes suggest an important role of vitamin E in maintaining the normal equilibrium of the dopaminergic nigrostriatal system.

Animals↗
PubMed2000

Follicular large cell lymphoma: long-term follow-up of 62 patients treated between 1973-1981.

PURPOSE: Investigators disagree on whether follicular large cell lymphoma (FLCL) behaves like other follicular lymphomas, with no plateau in the survival curve, or as a more aggressive but potentially curable lymphoma. We reported in 1984 results for 62 FLCL patients treated at our institution; the current report updates those results. PATIENTS AND METHODS: Sixty-two patients referred from 1973-1981, including fifteen (24%) patients with Ann Arbor stage I-II and forty-seven (76%) with stage III-IV FLCL. Seven patients received radiation (XRT) alone, forty patients XRT and chemotherapy, and fifteen patients received chemotherapy alone. RESULTS: The median follow-up was 14.7 years. The median survival was 5.1 years, with 21% alive at 15 years. The failure-free survival (FFS) at 10 years was 31%. Univariate analysis revealed that age, Ann Arbor stage, and the International Index correlated with survival. Performance status, number of platelets, and LDH correlated with failure-free survival. CONCLUSIONS: FLCL responds to doxorubicin-based regimens similarly to diffuse large cell lymphoma. Patients with FLCL have the potential for prolonged failure-free survival. Variables that predict the survival in aggressive lymphomas apply as well in this type of lymphoma.

Adult↗
PubMed2000

Histamine infusion induces a selective dopaminergic neuronal death along with an inflammatory reaction in rat substantia nigra.

We have evaluated the effects of a direct infusion of histamine, as mediator of inflammatory response, in substantia nigra, striatum, medial septum, and medial lemniscus. Injection of 100 and 250 nmol of histamine in substantia nigra produced a selective damage in dopaminergic neurons evidenced by the loss of tyrosine hydroxylase mRNA-expressing cells, tyrosine hydroxylase-immunolabeled-positive cell bodies, and dopamine and 3,4-dihydroxyphenylacetic acid levels. In parallel we found an acute inflammatory response manifested by a loss of glial fibrillary acidic protein-immunolabeled astrocytes and, at precisely the same area, an activation of microglia. In the striatum, only high doses (500 nmol) produced an evident terminal degeneration. The selective neurotoxicity of histamine for dopaminergic cells was demonstrated by the unaltered transcription of glutamic acid decarboxylase mRNA in substantia nigra. Moreover, intraseptal injection of 100 nmol of histamine failed to alter the pattern of choline acetyltransferase mRNA-expressing cells, and intraparenchymal injection of histamine in medial lemniscus failed to alter the pattern of serotonin-immunolabeled cells. We conclude that the substantia nigra is highly sensitive to histamine-derived neurotoxicity, where inflammatory processes mediated by histamine could be important in the pathological changes that lead to dopaminergic neuronal damage after histamine infusion.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2000

Ocular findings after ivermectin treatment of patients with high Loa loa microfilaremia.

Hemorrhages in the palpebral conjunctiva (HPCs) have been recorded in patients living in an area endemic for loiasis who developed serious reactions after ivermectin treatment. A study was designed to evaluate the frequency of these lesions, and to identify risk factors associated with their appearance. The conjunctivae of 1,682 patients who complained of reactions were systematically examined. HPCs were found in 41 patients. The initial mean Loa loa microfilaremia in the individuals with HPCs was 14,900 microfilariae (mf) per mL, as compared with 14.5 mf/mL in the other patients. Mansonella perstans microfilaremia and male gender were also associated with HPCs. Post-treatment fundus examinations were performed on 37 patients, and a close relationship was found between the occurrence of HPCs and the presence of retinal lesions. The vascular pathological processes leading to the ocular lesions may be similar to those which occur at the cerebral level in patients harboring high L. loa microfilaremia who develop neurologic troubles after ivermectin treatment. Retinal lesions may represent a special feature of the Loa-related encephalopathies useful for differential diagnosis, and the HPCs may be useful as an alarm sign to identify those individuals who might develop serious reactions after ivermectin treatment.

Adolescent↗
PubMed1999

Follicular large cell lymphoma: an aggressive lymphoma that often presents with favorable prognostic features.

It is debated whether follicular large cell lymphoma (FLCL) has a clinical behavior that is distinct from indolent follicular lymphomas, and whether there is a subset of patients who can be potentially cured. We report here our experience with 100 FLCL patients treated at our institution since 1984 with three successive programs. We evaluated the predictive value of pretreatment clinical features, including two risk models, the Tumor Score System and the International Prognostic Index (IPI). With a median follow-up of 67 months, the 5-year survival is 72% and the failure-free survival (FFS) is 67%, with a possible plateau in the FFS curve, particularly for patients with stage I-III disease. Features associated with shorter survival included age >/=60, elevated lactic dehydrogenase (LDH) or beta-2-microglobulin (beta2M), advanced stage, and bone marrow involvement. Stage III patients had significantly better survival than stage IV patients (P <.05). By the IPI and Tumor Score System, 80% of the patients were in the lower risk groups; both systems stratified patients into prognostic groups. Patients with FLCL have clinical features and response to treatment similar to that reported for diffuse large cell lymphoma. Prognostic risk systems for aggressive lymphomas are useful for FLCL. A meaningful fraction of patients may possibly be cured when treated as aggressive lymphomas.

Adult↗
PubMed1998

Influence of serotoninergic drugs on in vivo dopamine extracellular output in rat striatum.

In vivo microdialysis was used to investigate the mechanism behind the increase in extracellular dopamine (DA) induced by increase in extracellular serotonin (5-HT) level and 5-HT1 and 5-HT2 receptor activation. The following serotoninergic drugs were perfused in the absence or presence of nomifensine (5 microM) or tetrodotoxin (TTX; 2 microM): clomipramine (10, 500 and 1,000 microM), a selective 5-HT reuptake inhibitor; 8-OH-DPAT (50 and 500 microM), a 5-HT1A receptor agonist; and alpha-methyl-5-HT (1, 5 and 50 microM), a 5-HT2 receptor agonist. All the serotoninergic drugs studied increased DA extracellular output in a dose-dependent manner. The presence of nomifensine attenuated the effect of perfusion of clomipramine (500 microM) and completely abolished the effect of perfusion of 8-OH-DPAT (500 microM) and alpha-methyl-5-HT (5 microM) on DA extracellular output. Clomipramine (100-1,000 microM) perfusion produced a dose dependent increase in DOPAC extracellular output, which was stronger when clomipramine (500 microM) was co-perfused with nomifensine. 8-OH-DPAT and alpha-methyl-5-HT perfusion decreased DOPAC overflow. Addition of TTX to the perfusion fluid one hour before serotoninergic drugs perfusion, did not completely abolish the effect on dopamine extracellular output produced by the serotoninergic drugs. These data seem to indicate that increase in extracellular 5-HT level and 5-HT1 and 5-HT2 receptor activation increase in vivo DA extracellular output in the striatum mainly by a nonexocytotic mechanism involving DA uptake sites and, secondarily, by activation of 5-HT receptors.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

Exploratory space-time analysis of reported dengue cases during an outbreak in Florida, Puerto Rico, 1991-1992.

The spatial and temporal distributions of dengue cases reported during a 1991-1992 outbreak in Florida, Puerto Rico (population = 8,689), were studied by using a Geographic Information System. A total of 377 dengue cases were identified from a laboratory-based dengue surveillance system and georeferenced by their residential addresses on digital zoning and U.S. Geological Survey topographic maps. Weekly case maps were generated for the period between June and December 1991, when 94.2% of the dengue cases were reported. The temporal evolution of the epidemic was rapid, affecting a wide geographic area within seven weeks of the first reported cases of the season. Dengue cases were reported in 217 houses; of these 56 (25.8%) had between two and six reported cases. K-function analysis was used to characterize the spatial clustering patterns for all reported dengue cases (laboratory-positive and indeterminate) and laboratory-positive cases alone, while the Barton and David and Knox tests were used to characterize spatio-temporal attributes of dengue cases reported during the 1991-1992 outbreak. For both sets of data significant case clustering was identified within individual households over short periods of time (three days or less), but in general, the cases had spatial pattern characteristics much like the population pattern as a whole. The rapid temporal and spatial progress of the disease within the community suggests that control measures should be applied to the entire municipality, rather than to the areas immediately surrounding houses of reported cases. The potential for incorporating Geographic Information System technologies into a dengue surveillance system and the limitations of using surveillance data for spatial studies are discussed.

Adolescent↗
PubMed1997

Involvement of iron in MPP+ toxicity in substantia nigra: protection by desferrioxamine.

Desferrioxamine (DES) protective effect against 1-methyl-4-phenylpyridinium (MPP+) toxicity was evaluated by microdialysis in the substantia nigra. DES (1 microM to 10 mM) co-perfused with MPP+ (2.5 mM) on day 1, produced on day 2 a higher dopamine extracellular output after perfusion of MPP+ than in control-MPP+ perfusion experiments, in which no DES was administered on day 1. Both Ringer's perfusion alone (control-Ringer) and co-perfusion of DES (10 mM) with MPP+ (2.5 mM) on day 1 produced on day 2 similar increases in dopamine extracellular output after a second MPP+ perfusion. In the control-Ringer experiment, note that the MPP+ on day 2 is the first MPP+ perfusion. Perfusion of FeCl3 (200 microM) along with MPP+ (2.5 mM) and DES (100 microM) on day 1 completely abolished on day 2 the neuroprotective effect found with MPP+ (2.5 mM) and DES (100 microM). The ability of DES to protect against MPP+ toxicity may indicate a therapeutic strategy in the treatment of diseases when iron is implicated.

1-Methyl-4-phenylpyridinium↗