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Biomedical subjects

C Ramírez

Publications and source records attributed to C Ramírez.

At least 19 recordsLinked to original sources

Novel terpenoids from the West Indian sea whip Pseudopterogorgia elisabethae (Bayer). Elisapterosins A and B: rearranged diterpenes possessing an unprecedented cagelike framework.

Four diterpenes and a nor-diterpenoid, all of which possess unusual carbocyclic skeletons, were isolated from the hexane solubles of the West Indian gorgonian Pseudopterogorgia elisabethae. The structures and relative configurations of novel metabolites elisabethin D (2), elisabethin D acetate (3), 3-epi-elisabanolide (5), elisapterosin A (6), and elisapterosin B (7) were elucidated by interpretation of overall spectral data, which included 2D NMR correlation methods, IR, UV, and accurate mass measurements (HREI-MS and HRFAB-MS), chemical reactions, and X-ray diffraction analyses. The tetracyclic carbon skeleton of the elisapterosins is undescribed and constitutes a new class of C(20) rearranged diterpenes. Elisapterosin B displays strong in vitro anti-tuberculosis activity.

Animals↗

A marine diterpene with a novel tetracyclic framework from the West Indian gorgonian octocoral Pseudopterogorgia elisabethae.

[structure: see text] Colombiasin A (1) was isolated from an extract of the West Indian gorgonian octocoral Pseudopterogorgia elisabethae that showed strong inhibitorial activity against Mycobacterium tuberculosis H37Rv. Structure elucidation by interpretation of 2D-NMR spectroscopic data, IR, UV, and accurate mass measurements (HREI-MS) revealed that colombiasin A belongs to a previously undescribed class of C20 rearranged diterpenes possessing an intricate tetracyclic framework.

Animals↗

The Gregorio Marañón Hospital experience with vertical partial laryngectomies.

We present a retrospective study of 551 patients treated with conservative surgery for glottic carcinoma at the Gregorio Marañón Hospital between 1962 and 1996. In all, 12% of cases were locally advanced carcinomas. In early-stage carcinomas there were no statistical differences in 5-year survival between those treated by endoscopic laser resection, vertical hemilaryngectomy and radiotherapy. However, tumor recurrence after primary radiotherapy was higher (27%) than with conservative surgery (12%), while the voice preservation rate was significantly higher with surgery (83%) than with radiotherapy (72%). With locally advanced cancer, irradiated patients (to 60 Gy) had a 50% probability of recurrence with a very low chance for salvage by total laryngectomy (5-year survival rate, 38.5%). In contrast, partial laryngectomy could be performed on carefully selected patients, and the results for these patients were comparable to those for smaller lesions (with a 5-year survival rate of 81%).

Actuarial Analysis↗

Invasive disease caused by ciprofloxacin-resistant uropathogenic Escherichia coli.

To evaluate the invasiveness of ciprofloxacin-resistant Escherichia coli isolated from the urinary tract, the susceptibility to ciprofloxacin of Escherichia coli strains from patients with invasive urinary tract infection was compared with that of isolates from patients with noninvasive disease. In a 14-month period, 2054 different isolates of Escherichia coli were analyzed, of which 554 (27%) were resistant to ciprofloxacin. One hundred twelve (5.4%) strains were isolated from patients with invasive disease. Resistance was significantly less frequent in isolates from patients with invasive disease (4.5%) than in isolates from patients with noninvasive disease (28.3%) (OR, 0.12; CI 95%, 0.05-0.29; P<0.001). Most ciprofloxacin-resistant strains associated with invasive disease were isolated from bacteremic patients who had recently undergone an invasive procedure involving the urinary tract. Invasive disease is caused more frequently by ciprofloxacin-susceptible strains of Escherichia coli, suggesting that resistance to ciprofloxacin may decrease the invasiveness of uropathogenic Escherichia coli.

Adult↗

Elisabatins A and B: new amphilectane-type diterpenes from the West Indian sea whip Pseudopterogorgia elisabethae.

A chemical study of the hexane extracts of the gorgonian octocoral Pseudopterogorgia elisabethae collected in San Andrés Island, Colombia, led to the isolation of two highly conjugated amphilectane-type diterpenes, compounds 1 and 2. Their structures were established by spectroscopic studies, which included 2D NMR correlation methods, IR, UV, and accurate mass measurements (HREIMS).

Animals↗

Microglial cells during the lesion-regeneration of the lizard medial cortex.

The lizard medial cortex (lizard fascia dentata) is capable of neural regeneration after being lesioned by the anti-metabolite 3-acetylpyridine (3AP). This study was aimed at detecting microglial behaviour during the medial cortex lesion-regeneration process using tomato lectin histochemistry to label microglia (both with light and electron microscopy) and proliferating cell nuclear antigen (PCNA) immunocytochemistry to label proliferating cells. As expected, 1-2 days post-injection lectin-labelled microglia cells could not be observed in the medial cortex plexiform layers, but later (7 days post-injection) abundant lectin-labelled microglia cells re-populated the regenerating medial cortex. Abundant PCNA-immunolabelled nuclei were detected both in the subjacent ependymal neuroepithelium (neuroblasts, maximum at 2 days post-injection) as well as in some parenchymal cells which were also lectin-labelled (microglia, maximum at 7-15 days post-injection). Re-invasive microglia were also detected in the vicinity of ventricular ependymal lining, blood vessels and meninges. The electron microscope demonstrated that these microglial cells participate in cell debris removal, especially of neural granular cell somata. Other cell types related to microglia (mast cells, peri-vascular cells and meningeal cells) were also present during the scavenging process. Significant numbers of microglial cells remained in close relationship with the ependymal proliferative areas, even in control non-lesioned animals. This is indirect evidence for the working hypothesis that microglia are not only implicated in cell debris removal, but also in the regulation of newly generated neuroblast incorporation onto the cortical areas. Whether they phagocytose immature neuroblasts or induce cell death in them or even prevent their migration onto the principal layer areas are likely possibilities that remain to be proven.

Animals↗

Radial glia and cell debris removal during lesion-regeneration of the lizard medial cortex.

Intraperitoneal injection of the neurotoxin 3-acetylpyridine (3AP) induces a rapid degeneration of the medial cerebral cortex (lizard fascia dentata) granular layer and of its zinc enriched axonal projection (lizard mossy fibres). After 6-8 weeks post-lesion the cell debris have been removed and the granular layer is repopulated by neurons generated in the subjacent ependyma. Both processes, neuron incorporation and debris removal, seem to be crucial for successful regeneration. Scavenging processes in the lesioned mammalian CNS are usually carried out by microglia and/or astrocytes. In the lizard cerebral cortex there are no free astrocytes and the only glial fibrillary acid (GFAP) immunoreactive cells are radial glia-ependymocytes, similar to those present during mammalian CNS development. Ependymocytes, in addition to their help in vertical migrations of just generated immature neurons, built the cortical glial scaffold, insulate the blood capillaries, form the outer glial limiting membrane, thus playing an essential role in the lizard cortical blood-brain barrier. In this study, by means of GFAP-immunocytochemistry and electron microscopy, we have shown that radial glial cells participate actively in the removal/phagocytosis of cellular debris generated in the lesion process: mainly degenerated synapses, but interestingly, also some neuronal somata. Cell debris taken up by ependymocyte lateral processes seem to be progressively transported to either distal (pial) or proximal (ventricular) poles of the cell, where they result in lipofuscin accumulations. The hypothetical subsequent exchange of debris from ependymoglia by microglia/macrophages and Kolmer cells is discussed.

Animals↗

Age-related increase in expression of TGF-beta1 in the rat kidney: relationship to morphologic changes.

In the kidney, aging is characterized by the development of structural changes, including glomerulosclerosis and interstitial fibrosis. Transforming growth factor-beta1 (TGF-beta1) is known to play a critical role in the genesis of these alterations in pathologic conditions. The present experiments were designed to test the hypothesis that TGF-beta1 may be involved in the development of age-related histopathologic changes in rat kidney, and that captopril, an angiotensin-converting enzyme inhibitor, may influence the progression of glomerular and interstitial lesions. In this study, 3-, 18-, 24-, and 30-mo-old rats were examined, and an age-related increase in urinary protein excretion was found; plasma creatinine and systolic BP did not change. Significant structural changes, including glomerular sclerosis and interstitial fibrosis, were found in the group of aged rats (24- and 30-mo-old). Immunostaining for TGF-beta in the renal cortex interstitium was increased in the group of 24-mo-old rats, with a parallel increase in TGF-beta1 mRNA expression, measured with reverse-transcription PCR. Captopril-treated animals showed a statistically significant decrease in urinary protein excretion but no significant changes in BP. Moreover, captopril reduced the extent of interstitial fibrosis, but did not affect the degree of glomerulosclerosis. A significant inhibition of TGF-beta1 mRNA expression was observed in the captopril-treated animals. These findings suggest that TGF-beta1 may act as a fibrogenic growth factor that could be responsible, at least partially, for the renal interstitial fibrosis associated with aging. Treatment with captopril might delay the progression of these lesions.

Aging↗

Design and validation of a new image analysis method for automatic quantification of interstitial fibrosis and glomerular morphometry.

Interstitial fibrosis and morphologic changes in kidney glomeruli, the structural effects of many diseases, lead to significant pathologic alterations. A reliable and objective method to accurately quantify the extent of interstitial fibrosis and the degree of alteration in glomerular morphology is needed for both clinical practice and experimental work. The morphometric methods of quantification described to date are time-consuming and require trained personnel. This article describes the design and validation of an image analysis-based application (Fibrosis HR) for automatically and rapidly quantifying interstitial fibrosis and glomerular morphology in the same tissue section stained with Sirius red. The image processing algorithms described herein automatically segment interstitial fibrosis and mesangial matrix using automatic thresholding and morphologic filtering. The glomerular region is extracted by a simple interactive step and an automatic mathematical morphology algorithm, whereas the glomerular tuft is automatically segmented with automatic thresholding and a sequence of Boolean and mathematical morphology operations. All extracted areas are automatically quantified in absolute (microm2) and relative (%) values. For validation of this method, interstitial fibrosis, mesangial matrix, and glomerular and glomerular tuft areas were manually segmented and their quantifications statistically compared with those obtained automatically. Statistical analyses showed significant intra- and interoperator variability in manual segmentation of interstitial fibrosis, mesangial matrix, and glomerular tuft areas. Automatic quantifications of the same areas did not differ significantly from their mean manual evaluations. There was no significant intra- or interoperator variability in the interactive identification of the glomerular region. In conclusion, Fibrosis HR produces robust, fully reproducible, accurate, objective, and reliable quantifications, which facilitate the evaluation of in vivo experimental models of renal interstitial and glomerular pathologies and improve the accuracy of clinicopathologic analyses of renal diseases in human biopsies.

Algorithms↗

[Surface characteristics and antimicrobial sensitivity of clinical strains of Acinetobacter spp].

BACKGROUND: The treatment of nosocomial infections caused by Acinetobacter baumannii has been hindered by the easiness of this species to acquire antimicrobial resistance. AIM: To study surface hydrophobicity, the presence of capsule and antimicrobial susceptibility of nosocomial Acinetobacter spp strains. MATERIAL AND METHODS: Ninety four Acinetobacter spp strains isolated from a public hospital of Santiago, between July 1995 and April 1996, were studied. RESULTS: Compared to Acinetobacter genospecies 3 isolates, A baumannii isolates exhibited greater antimicrobial resistance, was uniformly susceptible to imipenem and highly resistant to other antimicrobials of clinical use. Most strains of biotypes 8 and 9 were hydrophilic and encapsulated, whereas those of infrequent biotypes and of Acinetobacter genospecies 3 were, with few exceptions, hydrophobic and not encapsulated. CONCLUSIONS: Capsule production might confer a greater virulence to Acinetobacter baumannii biotypes 8 and 9, and explain their higher prevalence in the studied hospital.

Acinetobacter↗

Effects of endotoxin on neurally-mediated gastric acid secretion in the rat.

The effects of a peripheral administration of E. coli endotoxin on neurally-mediated gastric acid secretion and the role of endogenous opioids or PAF receptors in endotoxin effects have been evaluated in the continuously perfused stomach of the anaesthetized rat. Gastric acid secretion stimulated by distension (20 cm H2O) was reduced dose-dependently by single intravenous bolus injection of endotoxin (0.1-10 microg kg(-1)). Doses of 5 microg kg(-1) induced a peak reduction of distension-stimulated acid output and significantly reduced the secretory response induced by an intravenous bolus of 2-deoxy-D-glucose (150 mg kg(-1)). This dose of endotoxin did not significantly modify mean systemic arterial blood pressure throughout the experimental period. Pretreatment with the opioid receptor antagonist naloxone (1 mg kg(-1) , i.v.) or the platelet-activating factor (PAF) receptor antagonist WEB 2086 (2 mg kg(-1), i.v.) did not reverse the inhibitory effects of endotoxin (5 microg kg(-1) , i.v.) on acid secretion stimulated by both distension and 2-deoxy-D-glucose. These findings suggest that endotoxin-induced acute inhibition of neurally-mediated acid responses, stimulated by gastric distension or administration of 2-deoxy-D-glucose, do not involve the activation of endogenous opioids or PAF receptors.

Animals↗

Chronic cyclosporin A nephrotoxicity, P-glycoprotein overexpression, and relationships with intrarenal angiotensin II deposits.

P-glycoprotein (P-gp) expels hydrophobic substances from the cell, including chemotherapeutic agents and immunosuppressants such as cyclosporin A (CsA) and FK506. Exposure of cultured renal tubular cells to CsA induces P-gp overexpression in cell membranes. Angiotensin II has recently been implicated as the principal factor responsible for progression of interstitial fibrosis induced by CsA. To investigate the in vivo relationships between histological lesions, P-gp overexpression, and intrarenal angiotensin II deposits, we developed a model of chronic CsA toxicity in Sprague-Dawley rats treated with 25 mg/kg/day CsA for 28 and 56 days and fed either a standard maintenance diet or a low-salt diet. Immunohistochemical methods were used to study the expression of P-gp in renal tubular cells and the appearance of intrarenal angiotensin II deposits. Rats treated with CsA developed chronic nephrotoxicity lesions that were more evident in the group fed the low-salt diet. Treatment with CsA induced overexpression of P-gp in tubular cells of the kidney that increased with time. We found that immunohistochemical expression of P-gp was slightly more severe in rats fed a low-salt diet. Intrarenal deposits of angiotensin II were more evident in rats treated with CsA; these deposits also increased with time. This finding was also more relevant in rats given the low-salt diet. The up-regulation of P-gp was inversely related to the incidence of hyaline arteriopathy (r = -0.65; P < 0.05), periglomerular (r = -0.58; P < 0.05) and peritubular fibrosis (r = -0.63; P < 0.05), and intrarenal angiotensin H deposits in animals with severe signs of nephrotoxicity (r = -0.65; P < 0.05). These results support the hypothesis that the role of P-gp as a detoxicant in renal cells may be related to mechanisms that control the cytoplasmic removal of both toxic metabolites from CsA and those originating from the catabolism of signal transduction proteins (methylcysteine esters), which are produced as a result of ras activation in presence of angiotensin II.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Immune response reduced by intense intellectual stress: changes in lymphocyte proliferation in medical students].

BACKGROUND: There is a relationship between stressful situations and the susceptibility towards certain diseases, probably mediated by immune system modifications. AIM: To study T lymphocyte proliferation in medical students during periods of differing academic stress. SUBJECTS AND METHODS: Blood samples were obtained from 42 medical students during a period of moderate academic stress, immediately before a final examination and after their summer vacations. T lymphocyte proliferation in response to 5, 10 and 20 mg/ml phytohemagglutinin was measured by the incorporation of 3H-thymidine, and plasma cortisol was measured by RIA. RESULTS: T lymphocyte stimulation index in response to all phytohemagglutinin concentrations was significatively lower in the period before examination than in the other two periods. There were no differences in the index between the period of moderate stress and after summer vacations. Plasma cortisol levels were 15.6 +/- 4.3, 18.6 +/- 5.8 and 16.7 +/- 5.1 mg/dl during the periods of moderate stress, before the examination and after vacations, respectively (p < 0.05 for the difference between examination and the other two periods). CONCLUSIONS: There is a decrease in lymphocyte proliferation and an increase in cortisol levels during a period of acute academic stress in medical students, suggesting that, the exposure of the healthy subjects to common stressful stimuli, may affect their immunocompetance.

Adult↗

Delaying and extending sleep during weekends: sleep recovery or circadian effect?

There is a well-known tendency to delay and prolong our sleep during weekends (Saturday and Sunday), with an advance and reduction of sleep during workdays (Monday to Friday). The objective of this work was to determine if the changes of sleep during weekends are produced by a partial sleep deprivation or a lack of entraining of circadian rhythms to an advanced phase, during workdays. The subjects were 52 undergraduate female students, mean age = 17.5 years, SD = 1.32. All students attended school following a regular schedule, from Monday to Friday. Two groups of students were studied: one attended school from 07:00 to 12:00 h (morning group, n = 30); the other attended school from 14:00 to 18:00 (afternoon group, n = 22). None of the students worked or was engaged in other activity with a fixed schedule. All kept a sleep-wake diary for 2 weeks, in which they recorded their bedtimes, wakeup times, and sleep-onset latencies. The morning group delayed 47.4 min [t(29) = 4.72, p < 0.0001] and prolonged their sleep 118.2 min [t(29) = 9.4, p < 0.0001] during weekends. Although the afternoon group had the opportunity to maintain a delayed phase and a long sleep time throughout the week, they delayed their bedtime by 24 min [t(21) = 2.99, p < 0.01] during weekends, without changing their sleep duration. The findings suggest that the prolonged sleep during weekends is due to reduction of sleep during workdays, whereas the delay of bedtime seems to be associated with a tendency of the human circadian system to maintain a delayed phase with respect to the solar daylight period.

Activities of Daily Living↗

Gingival overgrowth induced by nifedipine and cyclosporin A. Clinical and morphometric study with image analysis.

In this study, we developed a quantitative method with digital image analysis to evaluate the degree of gingival overgrowth (GO), and compared GO in kidney transplant patients treated with cyclosporin A (CsA) (n = 21) or CsA+nifedipine (n = 8) and a group of healthy controls (n = 30). The method was reproducible and reliable. Our findings showed significant differences in papillary and gingival surface between controls and transplant patients treated with GO inducers. Gingival overgrowth index also differed significantly between controls and each patient group (p < 0.01, Kruskal-Wallis test). The administration of the calcium channel blocker nifedipine potentiated the adverse effect of CsA: comparison of the morphometric findings revealed significant differences between patients treated with CsA alone and CsA+nifedipine in papillary area, dental area, and GO index (p < 0.01, Mann-Whitney U-test). We conclude that the method of image analysis we developed is useful in assessing the degree of GO.

Adult↗