Biomedical subjects

D Trujillo

Publications and source records attributed to D Trujillo.

16 recordsLinked to original sources

PubMed2004

Mitochondrial phylogeography of the long-eared bats (Plecotus) in the Mediterranean Palaearctic and Atlantic Islands.

Long-eared bats of the genus Plecotus are widespread and common over most of the western Palaearctic. Based on recent molecular evidence, they proved to represent a complex of several cryptic species, with three new species being described from Europe in 2002. Evolutionary relationships among the different lineages are still fragmentary because of the limited geographic coverage of previous studies. Here we analyze Plecotus mitochondrial DNA sequences from the entire Mediterranean region and Atlantic Islands. Phylogenetic reconstructions group these western Palaearctic Plecotus into two major clades which split at least 5 Myr ago and that are each subdivided into further subgroups. An 'auritus group' includes the traditional P. auritus species and its sister taxon P. macrobullaris (=P. alpinus) plus related specimens from the Middle East. P. auritus and P. macrobullaris have broadly overlapping distributions in Europe, although the latter is apparently more restricted to mountain ranges. The other major clade, the 'austriacus group,' includes the European species P. austriacus and at least two other related taxa from North Africa (including P. teneriffae from the Canary Islands), the Balkans and Anatolia (P. kolombatovici). The sister species of this 'austriacus group' is P. balensis, an Ethiopian endemic. Phylogenetic reconstructions further suggest that P. austriacus reached Madeira during its relatively recent westward expansion through Europe, while the Canary Islands were colonized by a North African ancestor. Although colonization of the two groups of Atlantic Islands by Plecotus bats followed very distinct routes, neither involved lineages from the 'auritus group.' Furthermore, the Strait of Gibraltar perfectly segregates the distinct lineages, which confirms its key role as a geographic barrier. This study also stresses the biogeographical importance of the Mediterranean region, and particularly of North Africa, in understanding the evolution of the western Palaearctic biotas.

Animals↗

PubMed2000

Immunotherapy with live BCG plus heat killed Leishmania induces a T helper 1-like response in American cutaneous leishmaniasis patients.

Previous work has shown that American cutaneous leishmaniasis (ACL) patients treated with viable BCG plus heat killed promastigotes of Leishmania amazonensis show the same rate of cure as patients receiving conventional chemotherapy. The treatment is safe and economical, but the immunological correlates of cure have not been examined. In the present study, T cell responses have been analysed in 43 ACL patients, including patient groups sampled before and after therapy, and in 10 endemic controls. Lymphocyte proliferation, interferon (IFN)-gamma and interleukin (IL)-5 responses to crude antigen (L. amazonensis, MEL; Mycobacterium tuberculosis PPD; M. bovis BCG) stimulation, and serum IL-5 levels, were analysed. In endemic volunteers, proliferative responses to BCG were high and IFN-gamma responses low. In contrast, localized cutaneous (LCL) and mucocutaneous (MCL) patients showed low proliferative and high IFN-gamma responses to BCG. Treatment enhanced the IFN-gamma response and further decreased the proliferative response to BCG, especially in MCL patients. LCL and MCL patients showed an increase in proliferative and IFN-gamma responses to MEL with treatment, but the response was not exaggerated in MCL patients, either before or after treatment, compared to LCL patients. IL-5 production was low in T cell assays, and > 62% of untreated patients had very low serum IL-5 levels. There were no significant changes in serum IL-5 with treatment. Overall results show enhanced antigen-specific IFN-gamma responses to the two components of the immunotherapy, live M. bovis BCG and heat killed L. amazonensis, which is consistent with a shift in balance of T cell response towards a T helper 1 response and clinical cure mediated by IFN-gamma.

Adolescent↗

PubMed1999

Metal contamination in illicit samples of heroin.

We analyzed 198 illicit heroin samples from Andalusia (southern Spain) to determine the contents of various metals (cadmium, calcium, copper, iron, manganese and zinc) with a view to investigating a new aspect of the drug purity and the conditions under which the drugs are used by addicts. Calcium was found in 93.4% of the samples and always at high concentrations, which can be ascribed to adulteration of the heroin by addicts with thinners and excipients containing salts of this metal such as calcium bicarbonate. Also, all samples were found to contain variable amounts of zinc and substantial amounts of iron, probably because it is the most common metal found in metal containers used in the extraction of morphine from the opium poppy. Only cadmium and, to a lesser extent, zinc, copper, and iron, are among the metals detected in heroin that can increase the inherent toxicity of the drug while always taking into account the maximum values.

Cadmium↗

PubMed1998

Pharmacokinetics, immunogenicity, and efficacy of dimeric TNFR binding proteins in healthy and bacteremic baboon.

Immunogenicity, pharmacokinetics, and therapeutic efficacy of three novel dimeric soluble tumor necrosis factor (TNF)-receptor I constructs [TNF-binding protein (bp)] were evaluated in 28 baboons, 12 of which were healthy and 16 were challenged with a lethal Escherichia coli bacteremia. The three constructs differed only in the number of extracellular domains of the TNF receptor I and were dimerized with polyethylene glycol. Although all three constructs had generally similar pharmacokinetics when administered to a naive animal, they differed quantitatively in their immunogenicity. Antibodies were detected more frequently, and titers were significantly higher (P < 0.05) in both healthy and septic baboons that received the 4.0-domain TNF-bp construct, compared with animals receiving the 2.6-domain construct. When the TNF-bp constructs were administered a second time (21 days later), the half-lives of the three constructs were significantly shorter in animals that had an antibody response after the first injection. In contrast, all three TNF-bp constructs were equally effective at improving outcome, blocking a systemic TNF-alpha response, and attenuating the cytokine responses when administered at a dose of 1.0 mg/kg body wt 1 h before a lethal E. coli infusion. The findings suggest that immunogenicity of TNF-bp constructs can be altered by changing the number of functional domains, without affecting their capacity to neutralize TNF-alpha and to abrogate TNF-mediated pathology.

Animals↗

PubMed1996

Least restrictive alternatives: do they really work?

Seclusion and restraint continue to spark debate regarding their therapeutic value and ethical, legal, and humanitarian implications, yet they remain frequently used forms of treatment in psychiatric settings. Identifying specific alternatives to seclusion and restraint use, teaching nursing staff how and when to use them, and determining their effect on patient outcome are important quality improvement issues. A quality improvement study conducted at a long-term care psychiatric facility identified alternatives that nursing staff used and their effect on reducing seclusion and restraint rates. A total of 773 incidents of disruptive behavior were managed with least restrictive alternatives and did not require the use of seclusion or restraint. One-to-one verbal intervention followed by medication as needed represented the most frequently used alternative. Total seclusion and restraint hours decreased by 31 percent, and restraint hours decreased by 47 percent.

Colorado↗

PubMed1994

Immune response in healthy volunteers vaccinated with killed leishmanial promastigotes plus BCG. I: Skin-test reactivity, T-cell proliferation and interferon-gamma production.

This study reports the results of a vaccine trial established to study the cellular immune responses in vivo (skin-test reactivity) and in vitro (T-cell proliferation and interferon-gamma production) to both leishmanial and mycobacterial antigens following vaccination of healthy volunteers from a leishmaniasis-endemic area with killed leishmanial promastigotes, with or without BCG (Bacille Calmètte-Guerin). Skin tests were performed using purified protein derivative of tuberculin (PPD) and leishmanial antigen in 692 volunteers, and 208 doubly negative subjects (< or = 7 mm induration) were selected to participate in the trial. The study subjects were divided into four vaccine groups: (A) killed promastigotes plus BCG, (B) BCG alone, (C) killed promastigotes alone, and (D) placebo. Three vaccine doses were administered at 6-10-week intervals. The skin-test responses to PPD and leishmanial antigen were reassessed at 4-6- and 12-18-month follow-ups. The results of this trial demonstrated that the combined vaccine, i.e. killed promastigotes of Leishmania plus BCG, results in the stimulation of an immune response to both leishmania and mycobacterial antigens in a high percentage of vaccines (> 85%), manifested either by skin-test conversion, lymphocyte proliferation and/or interferon-gamma production. This was evident after the first dose of vaccine for lymphocyte proliferation and interferon-gamma production and was maintained for a year after the three doses of vaccine. Group B (which received BCG alone), responded as well as group A to PPD but not as well to leishmanial antigen. The reverse was true for group C which received promastigotes alone. Group A attained a 38% leishmanin skin-test conversion at the 4-6-month follow-up, which was associated with double PPD/leishmanial antigen responder status. In contrast, a 35% skin-test conversion was found at the 12-18-month follow-up in group C (promastigotes alone), but this was not associated with responses to PPD. A significant percentage of conversion was observed in the placebo group at the 12-18-month follow-up, both to PPD (58%) and leishmanial (21%) antigens, which suggests either environmental exposure to mycobacterial or leishmanial antigens during the vaccine trial or, more probably, a response to the repeated leishmanial skin tests. Further studies are required to determine whether the presence of proliferative and/or interferon-gamma responses in the absence of a skin-test response are sufficient indicators of potential vaccine success.

Adolescent↗

PubMed1993

Serum levels of tumor necrosis factor in patients with American cutaneous leishmaniasis.

The purpose of this study was to evaluate serum levels of TNF-alpha in patients with either of the three clinical forms of American cutaneous leishmaniasis. The 86 patients examined were classified as having either the localized (LCL: 22 patients), mucocutaneous (MCL: 45 patients), or the rare diffuse (DCL: 19 patients) form of the disease. Our results show a significant increase in the mean level of TNF-alpha in the three groups of patients when compared to controls. MCL patients produce significantly higher levels of TNF-alpha than DCL patients. The proportion of individuals positive for serum TNF-alpha was significantly higher in both MCL and DCL patients than in the controls. No significant differences were found in the level of TNF-alpha when compared between before and after cure of 12 patients with MCL. There were no significant correlations between the level of TNF-alpha and the skin test diameter. The results will be discussed in terms of the pathogenesis of the disease in its different clinical forms.

Adolescent↗

PubMed1992

Leishmania chagasi antigens recognized in cured visceral leishmaniasis and asymptomatic infection.

Active visceral leishmaniasis is associated with antigen-specific immuno-suppression. However, cured patients develop a cellular immune response associated with resistance to reinfection. Recent studies have identified patients with asymptomatic or subclinical infections, which are also accompanied by an immune response. In order to identify subjects immune to Leishmania chagasi, we performed a skin-test survey in an endemic area in eastern Venezuela. The delayed-type hypersensitivity (DTH) response was assessed in patients cured of visceral leishmaniasis, as well as in their relatives and neighbors. Of the latter, 36 (34.2%) of 105 were positive and 26 (24.7%) of 105 gave intermediate responses. The DTH reaction correlated with age. The antigens recognized by a subgroup of cured patients, those with positive skin-test results, and controls (skin-test negative) were assessed by Western blotting with sera, and T cell immunoblotting with peripheral blood mononuclear cells. No consistent differences between the groups were noted in Western blots with L. chagasi antigens. T cell blots were performed on five patients from each group. For the cured patients and skin-test positive contacts, a significant proliferative response to fraction 12 (less than 20.5 kDa) was noted in four of five patients in each group. Cells from three of five cured patients and two of five skin-test-positive patients proliferated in response to fraction 4 (73-115 kDa). The response to other fractions was variable, with only a minority of patients responding to any one fraction. These data suggest that the antigens recognized by patients with evidence of immunity to L. chagasi are quite variable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1989

Autonomic innervation of reproductive organs: analysis of the neurons whose axons project in the main penile nerve in the pelvic plexus of the rat.

An understanding of the composition of the various nerves of the pelvic plexus is essential in the design of studies to explore the autonomic control of pelvic visceral tissues. As a correlate of this interest, the present study was designed to determine the composition of the main penile nerve in the pelvic plexus of the laboratory rat, an animal commonly used for studies of reproductive physiology. Retrograde tracing studies indicate that the main penile nerve contains neurons which project to the penile crura, the corpus spongiosum, and the bulbourethral glands. The main penile nerve is the major source of neurons which innervate the corpus spongiosum and bulbourethral gland and contains about one-third of all parasympathetic neurons which project to the penile crura. Dye placed on the proximal cut end of the main penile nerve indicates that neurons in the parasympathetic region of the spinal cord (L6-S1) and to a lesser extent a sympathetic region of the cord, L1-L2, provide preganglionic innervation to ganglion cells in the main pelvic nerve. Processes of neurons in dorsal root ganglia L6-S1 and of neurons in the abdominopelvic sympathetic chain course in the main penile nerve to unknown destinations. In many respects this presumed postganglionic fiber tract is essentially a region of the pelvic plexus which subserves extrapelvic visceral tissues.

Animals↗

PubMed1989

Cell-mediated immunity in localized cutaneous leishmaniasis patients before and after treatment with immunotherapy or chemotherapy.

In previous studies of the treatment of localized cutaneous leishmaniasis (LCL) we demonstrated that the therapeutic efficiency of immunotherapy (BCG plus promastigotes of Leishmania mexicana) is equal to that of chemotherapy (Glucantime), without causing the serious side-effects of the drug treatment. In the present study, various aspects of cell-mediated immunity, including the lymphoproliferative response, and leucocyte subpopulations were evaluated both before treatment and after cure in 39 LCL patients who had received immunotherapy (IT), in 34 submitted to chemotherapy (CT), and in 14 patients cured by the administration of BCG alone. We demonstrated evident signs of T-cell activation in cured patients who had received either CT or IT. For example, an increased expression of IL-2 receptors was observed in such patients, compared to their pretreatment values. Also, a significant percentage of patients showed augmented in-vitro responses to mitogen, and both in-vitro and in-vivo reactivity to leishmanial antigen. No evidence was found for the development of an exaggerated immune response to Leishmania parasites in the IT group, because the final level of immunological reactivity was comparable to the CT group. Neither was there any difference in terms of the final immune response between the patients cured by BCG treatment alone and the other groups. However, the therapeutic efficiency of BCG was lower and the mean cure time was longer. We conclude that IT is very useful in the treatment of LCL patients because of its high efficiency, low propensity to produce side-effects, and the fact that it does not induce a state of hyper-reactivity.

Adult↗

PubMed1989

Content and biosynthesis of cortisol in aldosterone-producing adenomas.

The content and biosynthesis of aldosterone and cortisol were examined and compared in the aldosterone-producing adenomas and adjacent adrenal glands from patients with primary aldosteronism that resulted from solitary, benign adrenocortical tumors (0.8 to 32.3 gm). Histologic examination of the six aldosterone-producing adenomas studied confirmed a predominance of cells resembling zona fasciculata rather than zona glomerulosa, as reported in previous studies. Measurement by radioimmunoassay of the tissue content of steroids preformed in vivo demonstrated that aldosterone was present in concentrations 8 times higher in aldosterone-producing adenomas (1.5 +/- 0.5 micrograms/gm tissue; mean +/- SEM) than in adrenal glands (0.2 +/- 0.06 micrograms/gm tissue). Cortisol concentration in aldosterone-producing adenomas (5.4 +/- 1.4 micrograms/gm tissue) was approximately one third that in adrenal glands (15.8 +/- 6.3 micrograms/gm tissue), but cortisol was by far the major steroid in both types of tissue. In vitro, the most important metabolic product quantitatively from 4-carbon 14-labeled cholesterol incubated with mitochondria plus microsomes and from 4-14C-labeled pregnenolone incubated with tissue slices was cortisol, formed in a time-dependent manner in both types of preparations; cortisol synthesis greatly exceed that of aldosterone in adrenal glands, but even in aldosterone-producing adenomas the formation of cortisol was at least 5 times greater than that of aldosterone. The fasciculata structure and dual biosynthetic capacity of aldosterone producing adenomas for cortisol and aldosterone are interpreted in the light of developing concepts of the roles of adrenocorticotropic hormone and of alterations in the microenvironment of the cell in the zonal differentiation of the normal adrenal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

PubMed1988

T-cell subpopulations, expression of interleukin-2 receptor, and production of interleukin-2 and gamma interferon in human American cutaneous leishmaniasis.

Leukocyte subpopulations, the expression of the interleukin-2 (IL-2) receptor, and the production of IL-2 and gamma interferon (IFN-gamma) were studied in the peripheral blood mononuclear cells of American cutaneous leishmaniasis patients that had been stimulated in vitro with either leishmanial antigen or mitogen (phytohemagglutinin M). The 75 patients examined were classified as having either the localized (LCL; 66 patients), mucocutaneous (MCL; 5 patients), or the rare diffuse (DCL; 4 patients) form of the disease. Patients with DCL, who are characterized by their defective cell-mediated immune response to leishmanial antigen, failed to express the IL-2 receptor and did not produce IFN-gamma when exposed to the antigen but did so when stimulated by phytohemagglutinin M. Both LCL and MCL patients showed strong proliferative responses to leishmanial antigen; these were by far the greatest in MCL patients. Both groups had significantly increased IL-2 receptor expression and IFN-gamma production after exposure to either antigen or mitogen, and these were highest in the MCL patients. Concerning the leukocyte subpopulations evaluated (CD2, CD4, CD8, CD20, MO2), the most significant findings were a decrease of both CD4+ cells and the CD4/CD8 ratio in MCL patients compared with the other groups. Considering IL-2 production, in response to phytohemagglutinin M both MCL and LCL patients showed amounts of IL-2 comparable to those of the controls. Our results help explain the anergy of T cells from DCL patients to leishmanial antigen, which could lead to a defective production of IFN-gamma and possibly contribute to their incapacity to kill the Leishmania parasite. Concerning MCL patients, the significantly increased expression of IL-2 receptor, decreased expression of the CD4 (helper-inducer of suppression) phenotype, and elevated IFV-gamma production might partially explains the state of hypersensitivity and mucosal damage exhibited by these patients.

Adult↗

PubMed1987

The adrenal gland of stranded whales (Kogia breviceps and Mesoplodon europaeus): morphology, hormonal contents, and biosynthesis of corticosteroids.

Histochemical assays, hormonal quantitation, and steroid biosynthetic studies were carried out with adrenal glands obtained from four stranded whales of two different species (Kogia breviceps and Mesoplodon europaeus), and selected comparisons were made with the results of similar studies of adrenals from terrestrial mammals (man, beef, rat). Histochemical chemical assays of the whale glands for succinic dehydrogenase activity (SDA) showed an intense SDA-positive reaction in the peripheral cortex, and an SDA-negative central medulla, a pattern similar to that found in terrestrial mammals; the whale adrenals, however, demonstrated a markedly pseudolobulated appearance because of a festooned corticomedullary junction. On radioimmunoassay of preformed cortical steroid hormones, corticosterone (B) exceeded cortisol (F) levels by a factor of 3 in the whale adrenals and aldosterone (Aldo) concentrations were 20-100 times lower than in the terrestrial mammals studied. HPLC determinations of preformed medullary catecholamines showed that, contrary to the findings in the terrestrial mammals studied, norepinephrine predominated over epinephrine and the levels of dopamine were much higher in the whale adrenals. In vitro, surviving sections of whale adrenals elaborated B from endogenous substrates, but not F or Aldo. Incubations of subcellular fractions of the whale adrenals with 14C-labeled precursors resulted in the isolation of several steroid intermediates (pregnenolone, progesterone, deoxycorticosterone) as well as the glucocorticoid end-product B, but again without evidence of the formation of either F or Aldo. In keeping with studies in terrestrial mammals, the enzymatic reactions involved in the conversion of [14C]cholesterol to B occurred under aerobic conditions, required the presence of an exogenous NADPH-generating system, and had identical subcellular localization in the whale adrenals. The process of steroid biosynthesis thus appears generally similar in aquatic and terrestrial mammals. It is possible that some of the unusual findings in the whale adrenals studies here may be related to the profound stress of stranding experienced by these marine mammals.

Adrenal Cortex Hormones↗

PubMed1987

Gamma interferon production induced by antigens in patients with leprosy and American cutaneous leishmaniasis.

In this study, we measured gamma interferon production in mononuclear cell cultures from patients with diverse forms of leprosy and American cutaneous leishmaniasis. We studied patients with lepromatous, borderline lepromatous, borderline, and borderline tuberculoid forms of leprosy, as well as a Mitsuda-negative contact. In leishmaniasis we studied patients with localized cutaneous, mucocutaneous, and diffuse cutaneous forms of the disease. High correlation was observed between gamma interferon production and lymphocyte proliferation assays in both diseases. Resistant forms of both diseases showed significant reactivity, while the severe progressive forms were characterized by insignificant responses in both assays. Localized cutaneous leishmaniasis is characterized by variability in gamma interferon production, which may be of prognostic value in longitudinal studies.

Cells, Cultured↗

PubMed1987

Demonstration of an indomethacin-sensitive mechanism regulating immune reactivity in American cutaneous leishmaniasis patients.

We investigated some aspects of the regulation of the immune response that were sensitive to the effect of indomethacin (INDO), an inhibitor of prostaglandin synthesis, in 84 patients with American cutaneous leishmaniasis (ACL), and in normal controls. The patients were classified on the basis of clinical and histopathological criteria as suffering localized (LCL), mucocutaneous (MCL) or diffuse (DCL) forms of the disease. The responses in vitro to mitogens (PHA and Con A) and leishmanial antigens were evaluated in the presence or absence of INDO. It was found that the drug significantly increased in vitro the mitogenic stimulation by PHA of peripheral blood mononuclear cells from LCL, MCL and DCL patients, but the effect was less evident in the controls. Considering specific responses to leishmanial antigens, we showed that in the presence of INDO, these were significantly increased in LCL patients, but not in MCL or DCL. Also, only in LCL was an inverse correlation found between the initial response to leishmanial antigen and the increase caused by INDO. Significant correlations were found between the INDO-induced enhancement of PHA and Con A responses in the patient groups, but not in the controls. In LCL patients there was a significant correlation between the increases caused by INDO of the mitogen and antigen responses. It can be suggested that an indomethacin-sensitive (prostaglandin dependent) suppressor mechanism operates in LCL patients, that is possibly responsible for the modulation of the immune response against the parasite. In MCL, where this suppressive mechanism is apparently not functional, the response to the parasite is intense, and a possible consequence of this could be tissue damage. Our results indicate, however, that the anergy observed in DCL patients is not due to an involvement of prostaglandins in the suppression of the specific immune response.

Adolescent↗

PubMed1985

Size aspects of metered-dose inhaler aerosols.

The aerodynamic size distribution of several bronchodilator and corticosteroid metered-dose inhaler (MDI) aerosols was estimated in both dry and humid (90% RH) air environments with a six-stage cascade impactor. The distribution of aerosol size that penetrated into a simulated lung model were also measured. The size distributions were approximately log-normal and ranged from 2.4 to 5.5 micron in mass median aerodynamic diameter (MMAD) with geometric standard deviation (GSD) of 1.7 to 2.5 in a dry environment. In humid air, MMAD increased from 1 to 26% above the dry air state, but GSD remained unchanged. The size of aerosol delivered by MDI that penetrated into a simulated lung model fell to 2.4 to 2.8 micron in MMAD (GSD, 1.9 to 2.2). In contrast to aerosols produced by MDI, MMAD of an aerosol of cromolyn sodium powder dispersed by a Spinhaler increased rapidly with increasing humidity, 5.6 +/- 0.3 micron in dry air and 10.1 +/- 0.8 micron in 90% RH air. Finally, the factors influencing size of MDI-delivered aerosols, including formulation, canister pressure, physicochemical properties of propellants, and design of the valve and actuator orifices are discussed. Effective delivery of MDI-generated aerosols into the lung is highly dependent on particle dynamics and jet flow, and no single parameter can produce a unique particle size and jet pattern.

Aerosol Propellants↗