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Biomedical subjects

M Castillo

Publications and source records attributed to M Castillo.

At least 145 records · Page 8Linked to original sources
PubMed1995

Disposition and covalent binding of ibuprofen and its acyl glucuronide in the elderly.

Ibuprofen is an over-the-counter nonsteroidal anti-inflammatory drug with a low incidence of severe adverse reactions. It is metabolized by oxidation to carboxyibuprofen and hydroxyibuprofen and by conjugation to an acyl glucuronide. In vitro studies have indicated that ibuprofen glucuronide is labile and reactive, forming covalent adducts with proteins. To verify the formation of ibuprofen-protein adducts in vivo, the pharmacokinetics of ibuprofen glucuronide and its covalent binding to plasma proteins were studied in five elderly patients who received long-term administration of oral doses of ibuprofen. Plasma levels of ibuprofen glucuronide were low relative to those of ibuprofen; the ratio of area under the plasma concentration versus time curve for the glucuronide relative to the parent drug was only 4%. Covalent binding of ibuprofen to plasma protein was observed in all patients, correlating well with the area under the plasma concentration versus time curve of ibuprofen glucuronide (r = 0.966). Compared with reports for other nonsteroidal anti-inflammatory drugs that form acyl glucuronides, plasma levels of ibuprofen-protein adduct are low during long-term administration. The observed lower reactivity in vivo is probably attributable to the greater stability of ibuprofen glucuronide relative to other acyl glucuronides.

Administration, Oral↗
PubMed1995

Gap junction turnover, intracellular trafficking, and phosphorylation of connexin43 in brefeldin A-treated rat mammary tumor cells.

Intercellular gap junction channels are thought to form when oligomers of connexins from one cell (connexons) register and pair with connexons from a neighboring cell en route to forming tightly packed arrays (plaques). In the current study we used the rat mammary BICR-M1Rk tumor cell line to examine the trafficking, maturation, and kinetics of connexin43 (Cx43). Cx43 was conclusively shown to reside in the Golgi apparatus in addition to sites of cell-cell apposition in these cells and in normal rat kidney cells. Brefeldin A (BFA) blocked Cx43 trafficking to the surface of the mammary cells and also prevented phosphorylation of the 42-kD form of Cx43 to 44- and 46-kD species. However, phosphorylation of Cx43 occurred in the presence of BFA while it was still a resident of the ER or Golgi apparatus yielding a 43-kD form of Cx43. Moreover, the 42- and 43-kD forms of Cx43 trapped in the ER/Golgi compartment were available for gap junction assembly upon the removal of BFA. Mammary cells treated with BFA for 6 h lost preexisting gap junction "plaques," as well as the 44- and 46-kD forms of Cx43 and functional coupling. These events were reversible 1 h after the removal of BFA and not dependent on protein synthesis. In summary, we provide strong evidence that in BICR-M1Rk tumor cells: (a) Cx43 is transiently phosphorylated in the ER/Golgi apparatus, (b) Cx43 trapped in the ER/Golgi compartment is not subject to rapid degradation and is available for the assembly of new gap junction channels upon the removal of BFA, (c) the rapid turnover of gap junction plaques is correlated with the loss of the 44- and 46-kD forms of Cx43.

Animals↗
PubMed1995

MR appearance of cerebral cortex in children with and without a history of perinatal anoxia: preliminary observations.

OBJECTIVES: The purpose of this study was to characterize the MR signal intensity of the cerebral cortex in children and to determine if the cortex is abnormal on MR images of patients with anoxia at birth (defined as persistent O2 saturation of less than 80% and requiring intubation or assisted ventilation for more than 24 hr). SUBJECTS AND METHODS: MR imaging was done in 10 patients with no history of anoxia and in nine patients with a history of anoxia. The T2 and T1 signals from the central gyri, the pre- and postcentral gyri, and the calcarine and insular regions of the gray matter were visually graded according to their intensity and to the degree that the low and high signal intensity each involved the entire length of that region. RESULTS: Low T2-signal intensity from the central gyri, the pre- and postcentral gyri, and the calcarine and insular regions of the gray matter was present on MR images made in patients without a history of anoxia and was absent in patients with a history of anoxia. High T1-signal intensity was seen in the central gyri in patients without a history of anoxia. Patients aged 1 year or older with a history of anoxia had no MR signal differences in any gray-matter region on either T1- or T2-weighted images. CONCLUSION: Low T2-signal intensity was seen in the central gyri, the pre- and postcentral gyri, and the calcarine and insular regions of the gray matter on MR images of patients with no history of anoxia but was not seen in those with a history of anoxia. Loss of the normal cortical T2 hypointensity may aid in establishing the diagnosis of anoxic brain injury.

Cerebral Cortex↗
PubMed1995

Disposition and reactivity of ibuprofen and ibufenac acyl glucuronides in vivo in the rhesus monkey and in vitro with human serum albumin.

The disposition of ibuprofen and ibufenac, an analog of ibuprofen with a history of severe adverse reactions, was investigated in Rhesus monkeys after oral administration. Plasma concentrations of the parent drugs and their glucuronides were measured by a direct HPLC method. Ibuprofen and ibufenac were rapidly absorbed and metabolized to their acyl glucuronides. The pharmacokinetic parameters of ibuprofen and ibufenac exhibited notable interanimal variability. Ibufenac tended to have a higher area under the plasma concentration vs. time curve (AUC), and its apparent clearance was lower. The plasma levels of acyl glucuronides were lower than parent drugs; the ratio of AUC in plasma for glucuronide/parent drug was 22.8% and 10.5% for ibuprofen and ibufenac, respectively. The degradation of ibufenac glucuronide in vitro was faster than ibuprofen glucuronide in aqueous buffer, human serum albumin, and human plasma solutions. Covalent binding of parent drug to protein via the acyl glucuronides was observed both in vitro and in vivo. The maximum protein adduct formed in vivo with ibufenac was 60% higher than found for ibuprofen, although exposure in plasma to its reactive acyl glucuronide, as measured by AUC, was lower. These data indicate that ibufenac glucuronide is a more reactive metabolite than ibuprofen glucuronide in vitro and in vivo.

Animals↗
PubMed1995

Dural cavernous angioma: MR features.

The imaging features of a cavernous angioma, which originated from the meninges, are presented. The patient harbored a second cavernous angioma within the brain parenchyma. Cavernous angioma should be included in the differential diagnosis of dural lesions, especially when other cavernous angiomas are present.

Adult↗
PubMed1995

MR of neurologically symptomatic newborns after vacuum extraction delivery.

We present the MR findings in three neurologically symptomatic newborns after vacuum extraction delivery. The lesions included subdural hematomas, one tentorial hematoma, and one intracerebellar hemorrhage. One patient had hydrocephalus that required shunting. We propose that the visualized abnormalities are probably the result of vertical stress leading to laceration of bridging veins, venous sinuses, and/or venous hemorrhagic infarctions.

Birth Injuries↗
PubMed1995

Nasopharyngeal nonossifying variant of ossifying fibromyxoid tumor: CT and MR findings.

The CT and MR findings of a nasopharyngeal nonossifying variant of an ossifying fibromyxoid tumor are presented. The findings are radiographically indistinguishable from more common malignant neoplasms encountered in this region. The tumor was isointense with muscle on T1-weighted images. On proton density- and T2-weighted images, the mass was mostly isointense with gray matter but contained some areas of lower intensity that might reflect the fibrous tissue component. The tumor eroded through the floor of the middle cranial fossa.

Adult↗
PubMed1995

MELAS syndrome: imaging and proton MR spectroscopic findings.

PURPOSE: To evaluate imaging findings in MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, strokes) syndrome for the presence and location of infarctions and the presence of lactate. METHODS: Eight patients were studied with MR (n = 8) and CT (n = 2). One patient underwent single-photon emission CT with technetium 99m hexamethyl-propyleneamine oxime and one patient had conventional catheter angiography. One fixed brain was studied with MR imaging. Five patients underwent single volume proton MR spectroscopy. Imaging studies were evaluated for atrophy, edema, and infarctions. Proton MR spectroscopy was visually analyzed for presence or absence of lactate. RESULTS: One patient showed a cerebral infarction, and later a second distant infarction developed. One patient showed a transient area of cortical edema. Two patients had small nonspecific periventricular white matter abnormalities and one patient had diffuse white matter hyperintensities. Two patients had nonspecific MR abnormalities (probably age-related changes), and two had normal MR findings. None had basal ganglia involvement. Proton MR spectroscopy showed presence of lactate in one case with transient cortical edema; in two cases with nonspecific (probably age-related) brain findings; and in two patients with normal MR findings. CONCLUSIONS: Patients with MELAS have a variety of MR findings. The fact that proton MR spectroscopy showed lactate in all five cases studied, regardless of MR findings, indicates that proton MR spectroscopy may be more sensitive in the detection of MELAS-associated abnormalities than MR imaging.

Adolescent↗
PubMed1995

Proton MR spectroscopy in patients with neurofibromatosis type 1: evaluation of hamartomas and clinical correlation.

PURPOSE: To use proton MR spectroscopy in patients with neurofibromatosis type 1 to determine: (a) the spectroscopic characteristics of hamartomas and compare them with that of gliomas; (b) whether differences exist between patients with and without learning disabilities; and (c) spectroscopic patterns in normal-appearing brain (by MR imaging) in patients with and without focal lesions. METHODS: Seventeen proton MR spectroscopy volumes were obtained in 10 patients with neurofibromatosis type 1 (including hamartomas, N = 7; normal-appearing brain, N = 10). Seven patients had learning disorders, and 3 were mentally normal. Ten healthy volunteers and 10 patients with pathologically proved gliomas (all grades) were also examined. N-Acetyl aspartate/creatine, creatine/choline, and N-acetyl aspartate/choline ratios were calculated for all samples. RESULTS: (a) Hamartomas showed higher N-acetyl aspartate/creatine, creatine/choline, and N-acetyl aspartate/choline ratios than gliomas. Hamartomas showed N-acetyl aspartate/creatine, creatine/choline, and N-acetyl aspartate/choline ratios similar to those of healthy volunteers. (b) No significant differences in N-acetyl aspartate/creatine, creatine/choline, and N-acetyl aspartate/choline ratios were found in patients who had neurofibromatosis type 1 with and without learning disabilities. (c) N-acetyl aspartate/creatine, creatine/choline, and N-acetyl aspartate/choline ratios were similar for patients who had neurofibromatosis type 1 with and without focal hamartomas and in healthy volunteers. CONCLUSIONS: (a) Hamartomas have a proton MR spectroscopy pattern different from that of glioma and similar to that of normal brain. (b) As performed in this study, proton MR spectroscopy did not show significant differences in patients who had neurofibromatosis type 1 with and without learning disabilities. (c) Patients who have neurofibromatosis type 1 with and without hamartomas seem to have normal intervening brain by proton MR spectroscopy when compared with healthy volunteers.

Adolescent↗
PubMed1995

Imaging of nasopharyngeal atresia.

CT and MR revealed a case of nasopharyngeal atresia, a malformation in which the soft palate is not formed, and the hard palate extends posteriorly to fuse with the anterior surface of the clivus, resulting in complete isolation of the nasal and oral cavities and the absence of a nasopharynx. We believe this rare anomaly results from abnormal persistence of the embryologic bucconasal plate and/or anomalous migration of the nasoseptal elements.

Abnormalities, Multiple↗
PubMed1994

Imaging in acute basilar artery thrombosis.

The aim of this study was to review the imaging features in acute (< 24 h) basilar artery thrombosis. CT and MR studies in 11 patients with clinical diagnosis of acute basilar artery thrombosis were retrospectively reviewed. MR angiography was obtained in 4 patients. Correlation with clinical symptoms was performed. Multiple cranial nerve palsies and hemiparesis were the most common clinical symptoms at presentation. CT revealed hyperdense basilar arteries (n = 7) and hypodensities in the posterior circulation territory (n = 8). In one instance, the infarction was hemorrhagic. MR imaging showed absence of flow void within the basilar in 6 patients and MRA (using both PC and TOF techniques) confirmed absence of blood flow in 4 basilar arteries. One week after presentation, 5 patients died. Autopsy was obtained in 1 case and confirmed the diagnosis of basilar artery thrombosis. Basilar artery thrombosis has fairly typical imaging features by both CT and MR. MRA may be used to confirm the diagnosis. Prompt recognition may lead to early thrombolytic treatment and may improve survival.

Acute Disease↗