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Biomedical subjects

E Rubio

Publications and source records attributed to E Rubio.

At least 37 records · Page 2Linked to original sources

Regio- and Diastereoselective Aldol Products through Three-Component Coupling Reactions of Difluoroboroxy Fischer Carbene Molybdenum Complexes.

The reaction of difluoroboroxy Fischer carbene complexes, vinyl ketones, and aldehydes leads to the regioselective formation of aldol-like products (see reaction scheme). The reaction also shows a high degree of diastereofacial selectivity when chiral aldehydes are used. These results show that this is a very attractive process since the regioselective formation of aldols from nearly symmetrical ketones still remains an unsolved problem.

Journal Article↗

beta-Trace protein in human cerebrospinal fluid: a diagnostic marker for N-glycosylation defects in brain.

As carbohydrate-deficient glycoprotein syndromes (CDGS) are multisystemic disorders with impaired central nervous function in nearly all cases, we tested isoforms of beta-trace protein (beta TP), a 'brain-type' glycosylated protein in cerebrospinal fluid (CSF) of nine patients with the characteristic CDGS type I pattern of serum transferrin. Whereas the serum transferrin pattern did not discriminate between the various subtypes of CDGS type I (CDGS type Ia, type Ic, and patients with unknown defect), beta TP isoforms of CDGS type Ia patients differed from that of the other CDGS type I patients. The percentage of abnormal beta TP isoforms correlated with the severity of the neurological symptoms. Furthermore, two patients are described, who illustrate that abnormal protein N-glycosylation can occur restricted to either the 'peripheral' serum or the central nervous system compartment. This is the first report presenting evidence for an N-glycosylation defect restricted to the brain. Testing beta TP isoforms is a useful tool to detect protein N-glycosylation disorders in the central nervous system.

Adolescent↗

A prospective study of adverse drug reactions in hospitalized children.

AIMS: There are few publications of adverse drug reactions (ADRs) among paediatric patients, though ADR incidence is usually stated to be higher during the first year of life and in male patients. We have carried out a prospective study to assess the extent, pattern and profile risk for ADRs in hospitalized patients between 1 and 24 months of age. METHODS: An intensive events monitoring scheme was used. A total of 512 successive admissions to two medical paediatric wards (47 beds) were analysed. The hospital records were screened daily during two periods (summer, 105 days and winter, 99 days), and adverse clinical events observed were recorded. RESULTS: A total of 282 events were detected; of these, 112 were considered to be manifestations of ADRs. The cumulative incidence was 16.6%, no differences being observed between periods. Although there were no differences between patients under and over 12 months of age, risk was found to be significantly higher among girls compared with boys (RR=1.66, 95% CI 1.03-2.52). The gastro-intestinal system was most frequently affected. The therapeutic group most commonly implicated was anti-infective drugs and vaccines (41.5%). The ADRs were mild or moderate in over 90% of cases. A consistent relationship was noted between the number of drugs administered and the incidence of ADRs. CONCLUSIONS: Hospitalized patients exhibited an ADR risk profile that included female sex and the number of drugs administered. No particular age predisposition was observed. The most commonly prescribed drugs are those most often implicated in ADRs in paediatric patients.

Child, Hospitalized↗

The effects of histamine on the isolated mouse uterus.

1. A study is made of the contractile and relaxant effects, and mechanism of action, of histamine on isolated uterus from mice treated with diethylstilboestrol, employing acetylcholine and adrenaline as contractile and relaxant standard agents. 2. Concentration-response curves for histamine agonists were obtained in the absence and presence of selective histaminergic blocking drugs (clemizole, ranitidine and thioperamide) and indomethacin. A number of experiments were carried out in uterus from reserpinised mice. Concentration-response curves for acetylcholine and adrenaline were also obtained in the absence and presence of their selective antagonist (atropine and propranolol). 3. In isolated oestrogenised mouse uterus, histamine and acetylcholine produced a concentration-related contractile response. When the uterus was precontracted with KCl, histamine at lower doses produced a slight contraction, though in the presence of clemizole it induced concentration-related relaxation, reminiscent of that produced by adrenaline. Atropine and propranolol antagonised the contractile and relaxant effects of acetylcholine and adrenaline, respectively. 4. In isolated uterus from reserpinised mice, histamine and 2-pyridylethylamine, but not 4-methylhistamine, produced a concentration-related contractile response. Ranitidine potentiated the contractile effect of histamine, though clemizole--in the presence of ranitidine--competitively antagonised the contractile effect of histamine (pA2 = 10.50 +/- 0.81). The concentration-relaxant curve of histamine in the presence of clemizole was not modified by ranitidine or indomethacin, but shifted to the right with thioperamide. The same displacement was also observed in the presence of clemizole plus ranitidine. 5. In mouse isolated uterus, histamine mainly produced contraction mediated by histamine H1-receptors, though the existence of histamine H2- or H3-receptors mediating relaxation could not be excluded.

Acetylcholine↗

Interhemispheric supratentorial intracranial pressure gradients in head-injured patients: are they clinically important?

OBJECT: It is generally accepted that the intracranial compartment behaves as a unicameral space in which intracranial pressure (ICP) is uniformly distributed. However, this concept has been challenged many times. Although there is general agreement on the existence of craniospinal and suprainfratentorial gradients, the existence of interhemispheric gradients is still a matter of debate. The object of this study was to reexamine the issue of interhemispheric supratentorial ICP gradients in patients with head injuries and the clinical significance of these gradients in their management. METHODS: The authors present the results of a prospective study conducted in 50 head-injured patients to determine the clinical significance of supratentorial ICP gradients. In each case a concurrent bilateral frontal intraparenchymatous device was implanted within the 6-hour window after computerized tomography (CT) scanning. According to CT criteria, each patient was categorized into one of three different groups: 1) diffuse lesions, in which no unilaterally measured volumes greater than 25 ml were present and the midline shift was 3 mm or less; 2) Focal A, in which added hemispheric volumes were greater than 25 ml and midline shift was 3 mm or less; and 3) Focal B, in which all patients with a midline shift greater than 3 mm were included. From the results of the entire group the authors were able to distinguish four different patterns of supratentorial ICP. In Pattern I, the intracranial compartment behaved as a true unicameral space with similar mean ICPs and pulse amplitudes in both hemispheres; in Pattern II, different mean ICPs and amplitudes were observed although ICP increases or decreases were congruent; and in Pattern III, patients with different mean ICPs, different ICP amplitudes, and no congruent increases or decreases of ICP were included. All (15 cases) but one patient with a diffuse lesion presented with ICP Pattern I. Fifteen patients with focal lesions showed a Type II pattern, whereas only one patient presented with a Type III pattern. In 10 patients, of whom all but one presented with a focal lesion, transient gradients that disappeared in less than 4 hours were also observed. CONCLUSIONS: In many patients with focal lesions, clinically important interhemispheric ICP gradients exist. In this subset, transient gradients that disappear with time are frequently observed and may indicate an increase in the size of the lesion. The clinical relevance of such gradients is discussed and guidelines for adequately monitoring ICP are suggested to optimize head injury management and to avoid suboptimal or even harmful care in patients with mass lesions.

Adolescent↗

Modulation of the chaperone heat shock cognate 70 by embryonic (pro)insulin correlates with prevention of apoptosis.

Insights have emerged concerning insulin function during development, from the finding that apoptosis during chicken embryo neurulation is prevented by prepancreatic (pro)insulin. While characterizing the molecules involved in this survival effect of insulin, we found insulin-dependent regulation of the molecular chaperone heat shock cognate 70 kDa (Hsc70), whose cloning in chicken is reported here. This chaperone, generally considered constitutively expressed, showed regulation of its mRNA and protein levels in unstressed embryos during early development. More important, Hsc70 levels were found to depend on endogenous (pro)insulin, as shown by using antisense oligodeoxynucleotides against (pro)insulin mRNA in cultured neurulating embryos. Further, in the cultured embryos, apoptosis affected mainly cells with the lowest level of Hsc70, as shown by simultaneous Hsc70 immunostaining and terminal deoxynucleotidyltransferase-mediated UTP nick end labeling. These results argue in favor of Hsc70 involvement, modulated by embryonic (pro)insulin, in the prevention of apoptosis during early development and suggest a role for a molecular chaperone in normal embryogenesis.

Amino Acid Sequence↗

Incidence of intracranial hypertension after severe head injury: a prospective study using the Traumatic Coma Data Bank classification.

UNLABELLED: Intracranial hypertension (ICH) is a frequent finding in patients with a severe head injury. High intracranial pressure (ICP) has been associated with certain computerized tomography (CT) abnormalities. The classification proposed by Marshall et al. based on CT scan findings, uses the status of the mesencephalic cisterns, the degree of midline shift, and the presence or absence of focal lesions to categorize the patients into different prognostic groups. Our aim in this study was to analyze the ICP evolution pattern in the different groups of lesions of this classification. PATIENTS AND METHODS: We present the results of a prospective study in 94 patients with severe head injury, in whom ICP was monitored for at least 6 hours. ICP evolution was classified into three different categories: 1) ICP always < 20 mm Hg, 2) Intracranial hypertension at some time during monitoring, but controlled by medical or surgical treatment, 3) Uncontrollable ICP. The ICP pattern was correlated with the final CT diagnostic category. CONCLUSIONS: 3 patients had a normal CT scan, and none of them presented intracranial hypertension. In diffuse injury type II, the ICP evolution may be quite different. Patients with bilateral brain swelling (Diffuse Injury III) have a high risk of increased ICP (63.2%). Although in our study the frequency of Diffuse Injury IV was low, all patients in this category had a refractory ICP. In the category of evacuated mass lesions, two thirds of the patients presented an intracranial hypertension. In one third, ICP was refractory to treatment. 85% of patients with a non-evacuated mass lesion showed an increased ICP.

Adult↗

The effects of epinine on arterial blood pressure and regional vascular resistances in anesthetized rats.

1. We carried out experiments in anesthetized rats to study the hemodynamic effects of intravenous injections of epinine. 2. Epinine (1-320 micrograms/kg) produced a biphasic effect on mean arterial blood pressure (n = 30). At doses lower than 40 micrograms/kg, arterial blood pressure decreased (by as much as 21.5 +/- 3.4%), though at higher doses it increased dose dependently (by as much as 73.2 +/- 14.5%). Epinine also produced bradicardia in a dose-dependent manner (by as much as 26.4 +/- 4.9%). Sulpiride (100 micrograms/kg) suppressed the hypotensive effect of epinine but did not change the hypertensive effect. In the presence of prazosin (1,000 micrograms/kg), arterial blood pressure remained significantly decreased at all doses of epinine. Neither sulpiride nor prazosin changed the bradycardic effect of epinine. 3. Prazosin produced a significant decrease in renal vascular resistance. Epinine (5 micrograms/kg) after prazosin reverted the effects of prazosin in renal vascular resistance, without any significant modification in the renal blood flows. However, 20 micrograms/kg epinine increased the renal vascular resistances and, moreover, produced a significant decrease in the blood flows of both kidneys. Neither prazosin nor epinine produced modifications in the intestinal vascular bed. 4. Although epinine possesses significant dopamine and alpha-adrenergic activities that are involved in the biphasic effect of the agent on mean arterial blood pressure in anesthetized rats, in the presence of prazosin, it is not possible to manifest dopaminergic activity involved in the increase in renal or mesenteric blood flow; this may be due to the low tone of the vascular wall induced by the alpha-adrenergic antagonist, though an alpha 2-activity cannot be discarded.

Anesthetics, Intravenous↗

In vivo insulin-dependent glucose uptake of specific tissues is decreased during aging of mature Wistar rats.

Aging has been associated with peripheral insulin resistance in both humans and rats. However, the specific tissues that become insensitive to insulin before glucose homeostasis is altered remain to be elucidated. In the present work we studied the glucose metabolic index of a number of tissues known to be insulin sensitive in 3- and 24-month-old Wistar rats by measuring 2-deoxy-D-[1-3H]glucose uptake both under euglycemic-hyperinsulinemic conditions and in the basal state. Analysis of the glucose infusion rate to maintain normoglycemia during the clamp confirmed that the old rats show overall insulin resistance at both saturating and subsaturating insulin concentrations. The maximal response of glucose uptake to insulin as well as insulin sensitivity in red and white quadriceps were unaltered in old rats. In contrast, glucose uptake by soleus and diaphragm was poorly stimulated in old animals, and a marked decrease in insulin sensitivity was observed in both tissues. In heart, only the sensitivity to the hormone, not the maximal response, was impaired in old rats. In white adipose tissue, no significant stimulation was detected. We conclude that during aging in Wistar rats and before fasting plasma insulin and glucose levels become altered, specific tissues develop insulin resistance, whereas other remain insulin sensitive. We postulate that fat tissue plays a qualitative important role in eliciting the insulin resistance in old animals. Due to the metabolic characteristics of the aged Wistar rat, the changes reported might reflect what occurs in nonobese elderly humans, nongenetically committed to develop type 2 diabetes.

Adipose Tissue↗

Are the adverse drug reactions of amoxycillin and amoxycillin-clavulanic acid similar?

UNLABELLED: In an attempt to assess the relative toxicity of amoxycillin and amoxycillin-clavulanic acid, we compared the adverse drug reactions reports collected using the spontaneous reporting system of a Regional Drug Surveillance Centre of Spain for both drugs between November 1986 and December 1992. During the 7-year period 1986-92, the 247 reports of amoxycillin-clavulanic acid represent twice the number of reports of amoxycillin alone, and the number of reports related with sales received concerning the association were higher than those concerning amoxycillin alone. The adverse effects classified as severe were quantitatively and qualitatively similar for both drugs and gastrointestinal and skin are the most common system-organ affected by both drugs. With amoxycillin-clavulanic acid there is a higher proportion of stomatological reactions reported and a later onset of adverse drug reactions related with oropharyngeal lesions, and the reaction of the resistance mechanism when compared with the other organs and systems affected. The duration of the adverse drug reactions to amoxycillin-clavulanic acid is longer than for amoxycillin alone. IN CONCLUSION: (i) the adverse drug reactions profile of both drugs is different; (ii) the higher reporting rate for amoxycillin-clavulanic acid may be due to more recent marketing; and (iii) amoxycillin-clavulanic acid produces proportionately more gastrointestinal and fewer skin adverse reactions than amoxycillin alone.

Journal Article↗

Arterio-jugular differences of oxygen (AVDO2) for bedside assessment of CO2-reactivity and autoregulation in the acute phase of severe head injury.

Autoregulation and CO2-reactivity can be impaired independently of each other in many brain insults, the so-called 'dissociated vasoparalysis'. The theoretical combination of preserved CO2-reactivity and impaired or abolished autoregulation can have many clinical implications in the daily management of brain injured patients. To optimize their treatment, a bedside assessment of autoregulation and CO2-reactivity is desirable. When cerebral metabolic rate of oxygen is constant, changes in arterio-jugular differences of oxygen (AVDO2) reflect changes in CBF. In these situations relative changes in AVDO2 can be viewed as inverse changes in CBF and used as an evaluation method of CO2-reactivity and autoregulation. In 39 consecutive severe head injury patients with a mean age of 28 +/- 17 years and a diffuse brain injury, cerebrovascular response to changes in pCO2 was tested in the acute phase after injury (18 +/- 8 hours). In 28 of those cases autoregulation was also assessed. A relative CBF value (1/AVDO2) was calculated from baseline AVDO2 and was expressed as 100%. Changes in 1/AVDO2 after inducing pCO2 changes give a good estimate of changes in global CBF. Two different indexes were calculated for CO2-reactivity: 1) absolute CO2-reactivity (CO2RABS) and 2) percentage reactivity (CO2R%). CO2R% was used to separate patients with impaired/abolished CO2-reactivity from those with preserved CO2-reactivity. Patients with CO2R% above 1% were considered in the intact CO2-reactivity group and patients in whom CO2R% was below or equal to 1% were included in the impaired/abolished CO2-reactivity group. Only five cases (12.8%) presented an impaired/abolished CO2-reactivity. AVDO2 response to induced hypertension was studied in a subset of 28 patients. Phenylephrine was used to increase MABP about 25%. All AVDO2 values were corrected for changes in pCO2. Patients with changes in 1/AVDO2 less than or equal to 20% were included in the intact autoregulation group. Patients with estimated CBF changes above 20% were classified as having an impaired autoregulation (impaired/abolished). In 12 patients (43%) autoregulation was intact. In the remaining 16 patients (57%) autoregulation was imparied. Of the 28 cases, CO2-reactivity was impaired in only five cases. All patients with an impaired CO2-reactivity also had an impaired autoregulation. Monitoring relative changes in AVDO2 permits a reliable study of CO2-reactivity and autoregulation at the bedside. Introducing these variables into the day-to-day management should be considered in treatment protocols.

Adolescent↗

A prospective study of adverse drug reactions as a cause of admission to a paediatric hospital.

1. A total of 512 consecutive paediatric hospital admissions of children 2 years old or less were evaluated to assess the extent and pattern of admission caused by suspected adverse drug reactions (ADRs). the proportion of suspected ADRs related to hospital admissions was 4.3%. 2. The organ-systems most commonly implicated were the central nervous system (40.5%), digestive system (16.7%), and skin and appendages (14.3%). Together, they accounted for 71.5% of admissions attributed to ADRs. The most common clinical manifestations inducing admission were convulsions (4 cases), dizziness (4), vomiting (3), and tremor, fever, itching and apnoea (2 cases each). 3. The four classes of drugs most frequently suspected in admissions due to ADRs were respiratory drugs (35%), anti-infective agents (25%), drugs active on the central nervous system (15%) and drugs used in dermatology (10%). The most common drugs related to ADRs were a combination of chlorpheniramine, diphenhydramine, phenylephrine, guaiphenesin and salicylic acid (4 cases), followed by fenoterol, adrenaline, paracetamol, DTP vaccine and antipolio vaccine (2 cases each). 4. There were no significant differences between children older and younger than 1 year (odds ratio 0.89; 95% CI 0.37-2.17) or between the sexes as regards hospital admittance due to suspected ADRs (odds ratio 1.94; 95% CI 0.72-5.42). 5. The results of this kind of study may be influenced by patterns of drug utilization. Nevertheless, the lack of specific studies of drug effects in young children makes it desirable to carry out pharmacoepidemiological studies in this age group.

Child, Preschool↗

Isolated human colon strips as a pharmacological tool.

The spontaneous activity of isolated human colon strips was studied to obtain homogeneous results with a reproducible model. The strips of macroscopically normal appearance were mounted in an organ bath containing Krebs solution at 32 degrees C or Tyrode solution at 37 degrees C. Mechanical activity was recorded by an isometric transducer. Spontaneous motility did not occur in all preparations. Moreover, when observed, it could not always be evaluated. The percentage of strips with spontaneous activity was lower with Tyrode solution than with Krebs solution (65 vs. 81%). KC1 did not induce a plateau contraction. Acetylcholine induced concentration-dependent contractions, with a significantly different pD2: 4.43 +/- 0.39 and 5.59 +/- 0.16 for Krebs and Tyrode, respectively. Isoprenaline abolished spontaneous motility in Krebs solution. Only 20% of specimens presented evaluable motility. Krebs solution may be the best conditions for studying the effects of drugs on spontaneous motility, while Tyrode solution can be used to investigate the effects of contractile agents.

Acetylcholine↗

No evidence for dopamine-induced relaxation in isolated human mesenteric arterial strips from elderly patients.

1. We investigate the effects of dopamine in isolated mesenteric artery from elderly patients. 2. Noradrenaline (10(-11) to 10(-4) M) and dopamine (2.7 x 10(-6) to 1.4 x 10(-3) M) induced a concentration-dependent contraction that was antagonized by prazosin. Fenoldopam (10(-8) to 10(-4) M) and clonidine (10(-9) to 10(-4) M) did not produce any contractile effects. 3. Potassium chloride (80 mM) produced a well-maintained plateau contraction and dopamine-induced contraction in these conditions, which was decreased by prazosin (10(-8) M). Neither fenoldopam nor isoprenaline (10(-10) to 10(-5) M) modified the well-maintained plateau. 4. Our results suggest that post-synaptic dopamine receptors are not present in this preparation but alpha1-adrenoceptors are present.

Aged↗