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Biomedical subjects

M A Castro

Publications and source records attributed to M A Castro.

At least 55 records · Page 3Linked to original sources

Methyl ethers of podophyllotoxin-related cyclolignans.

Methyl ethers of podophyllotoxin [1] and its epimers at positions 7 and 8' were obtained through the corresponding chlorinated or brominated derivatives at position 7. Additionally, the corresponding diol methyl ethers were obtained by reducing the lactone with LiAlH4. 7-O-Methylepipicropodophyllotoxin [12], 7-O-methylpicropodophyllotoxin [13], the diol methyl ethers 15-18 and the corresponding diacetates are described here for the first time. Most of the cyclolignans obtained were evaluated for their cytotoxic activity.

Animals↗

Antibodies to the cloned mu-opioid receptor detect various molecular weight forms in areas of mouse brain.

Polyclonal antibodies directed against the amino-terminal portion of the cloned rat mu-opioid receptor (muOR) were raised in rabbits. The antibodies diminished the specific binding of 125I-Tyr27-beta-endorphin-(1-31) (human) and [3H][D-Ala2,N-MePhe4,Gly-ol5]enkephalin, but not that of the delta OR-selective ligand [3H][D-Pen2,5]enkephalin, to mouse brain membranes. The intracerebroventricular administration to mice of affinity-purified anti-muOR IgGs impaired the antinociception produced by the muOR agonists [D-Ala2,N-MePhe4,Gly-ol5]enkephalin and morphine and the mu/delta OR agonists beta-endorphin-(1-31) and [D-Ala2,D-Leu5]enkephalin, when studied 24 hr later in the tail-immersion test. Antinociception produced by the delta OR-selective agonists [D-Pen2,5]enkephalin and [D-Ala2]deltorphin II was fully displayed in these mice. Immunoblots of sodium dodecyl sulfate-solubilized membranes from mouse central nervous system regions revealed protein bands of M(r) 43,000, 51,000, and 58,000. Also detected were bands of higher molecular weights, 100,000 and 114,000, which probably corresponded to dimeric forms, because they disappeared after sonication of the solubilized tissues. This immunoreactivity was present in regions of mouse central nervous system and was barely detected in NG108-15 cells. After treatment of the solubilized material with endoglycosidase F, the antibodies labeled a band of M(r) 43,000, coincident with the weight of the cloned muOR. These results confirm the existence of several molecular forms of the muOR due to glycosylation.

Amino Acid Sequence↗

Antineoplastic and antiviral activities of podophyllotoxin related lignans.

28 cyclolignans, most of them derived from podophyllotoxin, have been evaluated for their antineoplastic and antiviral activities. They were subjected to screening against P-388 murine leukemia, A-549 human lung carcinoma, and HT-29 colon carcinoma, while antiviral assays were performed on herpes simplex virus type I infecting fibroblasts of monkey kidney (HSV/CV-1) and on vesicular stomatitis virus infecting fibroblasts of hamster kidney (VSV/BHK). A number of substances were active in both groups of assays at concentrations below 1 microM; deoxypodophyllotoxin (1) being the most potent compound in all cases.

Animals↗

Antibodies raised against the N-terminal sequence of delta opioid receptors blocked delta-mediated supraspinal antinociception in mice.

A polyclonal antiserum directed against the first 16 amino acids of the N-terminal sequence of the murine delta opioid receptor was raised in rabbits. The intracerebroventricular (i.c.v.) injection to mice of the anti delta receptor IgGs impaired the antinociception produced by DPDPE, [D-Ala2]-Deltorphin II, DADLE and beta-endorphin-(1-31) when studied 24 h later in the tail-flick test. Antinociception produced by morphine and DAMGO was fully expressed in mice undergoing this treatment. The selective delta antagonist ICI 174864 (0.8 nmols/mouse, i.c.v.) significantly reduced the antinociceptive activity of opioids to the extent observed after giving the antibodies. ICI 174864 did not decrease further the antinociception that remained after the anti delta receptor serum. The specific binding displayed by 3 nM [3H]-DPDPE was reduced in membranes pre-incubated with the antiserum, whereas no change could be detected for 0.6 nM [3H]-DAMGO labelling mu receptors. This experimental approach revealed the delta component of opioid-evoked supraspinal antinociception in mice.

Amino Acid Sequence↗

AIDS knowledge and sexual behavior among Mexican gay and bisexual men.

Little knowledge exists about AIDS and Human Immunodeficiency Virus (HIV) infection among Latin American gay males. In Latin America, sexual transmission from man to man is the leading cause of HIV infection. In Mexico, which ranks third in number of AIDS cases in the Americas, more than three-quarters of the cases are due to sexual transmission; among these cases, 35% and 23.7% are due to homosexual and bisexual male practices, respectively. A sample of 200 individuals from Juarez, Mexico, a city on the U.S. border, was interviewed. Information about their AIDS knowledge, sexual behavior, and condom use was obtained. Factory workers and individuals who meet sexual partners in the streets reported more sexual partners than workers in service or professional occupations and those who meet their partners in bars and discos. Number of sexual partners and respondents' age were inversely associated with condom use. Implications for HIV prevention are discussed.

Acquired Immunodeficiency Syndrome↗

Gx/z and Gi2 transducer proteins on mu/delta opioid-mediated supraspinal antinociception.

Intracerebroventricular (i.c.v.) administration of immune sera raised against Gi2 alpha subunits to mice, significantly reduced the supraspinal antinociceptive effect of opioids when evaluated 24 h later in the tail-flick test. Antisera directed against Gi1 alpha subunits did not modify this opioid activity. In mice injected with sera anti-Gx/z alpha, the mu-preferential agonists, DAMGO and morphine, and the endogenous mu/delta opioid peptide beta-endorphin-(1-31) displayed a reduced antinociceptive activity, whereas, the potency of the delta-selective agonists DPDPE and [D-Ala2]Deltorphin II, was not altered. This reduction was present for 3 to 7 days and returned to the control values after 10 days. Anti-Gi2 alpha and anti-Gx/z alpha, but not anti-Gi1 alpha, reduced the specific binding of [3H]DAMGO to the opioid receptor in PAG. These results suggest the ability of the mu receptor to interact in vivo with different classes of G transducer proteins (Gx/z/Gi2) to produce an effect. This work also indicates a functional role of the pertussis toxin insensitive Gx/z protein, on the mu-mediated (but not delta-mediated) supraspinal antinociception in mice.

Amino Acid Sequence↗

Antineoplastic and antiviral activities of some cyclolignans.

Nineteen cyclolignans of varied structures, most of them isolated from Juniperus sabina leaves, were evaluated for their antineoplastic and antiviral activities. They were subjected to screening against P-388 murine leukemia, A-549 human lung carcinoma, and HT-29 colon carcinoma, while the antiviral assays were performed on herpes simplex virus type 1 infecting fibroblasts of monkey kidney (HSV-1/CV-1) and on vesicular stomatitis virus infecting fibroblasts of hamster kidney (VSV/BHK). A number of substances were active in both types of assays at concentrations below 1 microgram/ml; deoxypodophyllotoxin and beta-peltatin A methyl ether being the most potent compounds in all cases, with IC50 values in the range 2.5-4 ng/ml for the three neoplastic systems.

Animals↗

[Mediastinal tuberculosis as a cause of fever of unknown origin].

Tuberculosis is the most frequent cause of fever from unknown etiology. On the other hand, mediastinal tuberculous adenopathy (TBM), without associated pulmonary affection is a rare form of presentation among adults, generally evolving with sustained fever until a thoracic radiology is performed showing mediastinal enlargement. We present a case which started as fever from unknown etiology (FUE), given that, according to the thoracic radiology performed one month after the onset of fever, no mediastinal affection was observed.

Adult↗

[Immunoglobulins, beta-2 microglobulin and lymphocyte subpopulations in patients addicted to parenteral drugs (IVDA)].

Disorders in serum immunoglobulins, beta-2 microglobulin and lymphocyte subpopulations in parenterally drug-addict patients (PDAP) are analyzed. The study is divided in three parts. In the first one, a group of 33 HIV-negative PDAP without intercurrent diseases is compared with a control group of healthy non-addict persons. In the second part, the differences between a group of 58 HIV-negative PDAP and a group of 95 HIV-positive PDAP are studied. In the third part, the differences between the group of HIV-negative PDAP without associated procedures and a subgroup of HIV-positive patients including 31 asymptomatic carriers in phase II, are studied. No statistically significant differences were detected between the control group and the HIV-negative PDAP group. The HIV-positive PDAP group showed lymphocytes CD3, CD4 and a CD4/CD3 ratio statistically lower than the HIV-negative group, as well as a significant increase of the immunoglobulin IgG and beta-2 microglobulin. The same results were obtained when the subgroup of HIV-positive patients in phase II was compared with the group of HIV-negative PDAP without intercurrent diseases. According to these results, we conclude that the immunological disorders detected in PDAP patients seem to be more related with the infection by the human immunodeficiency virus and with other associated infections than with the drug-addiction itself.

Adult↗

[Hospitalizations because of drugs: a prospective study].

A study was carried out during five months in La Paz Hospital with the objective to know the proportion of admissions due to an adverse reaction to pharmaceutical drugs (RAM) or due to an acute drug intoxication. For this purpose the reports of all patients seen at the Medical Emergency Room were analyzed on a daily basis. Out of 1,847 patients who needed hospital admission during this time period, 88 (4.8%) were considered to need so due to RAM or an acute intoxication. Out of 145 acute intoxications treated, 16 patients (0.9% of total admissions) had to be hospitalized. RAM constituted 3.9% of admissions, with upper GI tract hemorrhages the most frequent cause (62.5%; 72 cases). The groups of drugs responsible in most RAM were the analgesics and NSAIDs, in particular acetylsalicylic acid, followed by hypoglycemic drugs and digoxin.

Acute Disease↗

Sodium-dependent and sodium-independent nicotine-evoked catecholamine release from cat adrenals.

Cat adrenal glands were stimulated with nicotine under Na-free conditions; subsequently, Na was gradually introduced as a continuously increasing gradient from 0 to 134 mM. With this experimental approach two catecholamine secretory peak responses were obtained: one was Na-independent and the second was dependent of this cation. This second response was greater in magnitude than the first and selectively blocked by (+)PN200-110, a potent dihydropiridine Ca channel blocker. The results suggest that Na, although not essential to evoke some degree of secretion, plays, however, a prominent role in amplifying the nicotine-secretory response by causing cell depolarization and opening of voltage-dependent Ca channels.

Adrenal Glands↗

[Adverse reactions to drugs as a reason for consulting the emergency service of a general hospital].

The reports from the emergency service of La Paz General Hospital were daily reviewed for 4 months to investigate the number of consultations which, on the judgement of the physician on care, were due to adverse reactions to drugs. An overall number of 11,326 patients consulted. In 438 (3.9%) it was considered that the consultation was due to one or more definite, likely or possible adverse drug reactions. In 69 patients (15.8%), the reactions were considered to be severe, and 54 (12.3%) required admission; 59 reactions (13.4%) were moderate, and 310 (70.8%) were mild. The most common localizations were the skin and its appendages (37.7%) and gastrointestinal tract (25.3%). The most commonly implicated pharmacologic groups were analgesic and non-steroidal anti-inflammatory drugs (33.6%) and antimicrobials (22.1%). The incidence of adverse reactions was significantly higher in women (4.4% vs 3.3% in males, p less than 0.01). Depending on the age groups (14-29, 30-59, greater than or equal to 60 years) the incidence of nonallergic adverse reactions was significantly higher in patients aged 60 years or more (1.5%, 2%, 2.9%; chi 2 = 15.2, gl = 2, p less than 0.001). In presumably allergic adverse reactions, the incidence was significantly higher among those under 30 years (2.9%, 2.2%, 0.5%; chi 2 = 50.2; gl = 2, p less than 0.0001). The incidence of severe adverse reactions was significantly higher in patients over age 60 years (0.2%, 0.6%, 1.2%, chi 2 = 29.2, gl = 2, p less than 0.001). In 32% of cases the adverse reactions might have been prevented.

Adolescent↗

The key role of sodium in the ouabain-mediated potentiation of potassium-evoked catecholamine release in cat adrenal glands.

1. The effect of [Na]o on the catecholamine release evoked by K in ouabain pretreated, isolated adrenal glands of the cat, was investigated. 2. Reduction of [Na]o to 70, 50 and 25 mM, with sucrose as a substitute, did not modify the spontaneous catecholamine release but progressively increased the K (17.7 mM)-evoked secretory response. 3. Ouabain pretreatment (100 microM; 10 min) greatly increased the K (17.7 mM)-evoked catecholamine secretory response in glands perfused with normal Krebs. Such an increase was still seen in glands perfused with 70 mM Na-containing solution but disappeared when [Na]o was reduced to 25 and 10 mM. 4. Preperfusion of non-ouabain treated glands with Li-enriched Krebs, for a 40 min period, caused an increase in the K (17.7 mM)-evoked secretory response which was dependent on [Li]o and essentially similar to that induced by ouabain pretreatment. 5. Ouabain treatment (100 microM; 10 min) of glands perfused with normal Krebs evoked a long lasting catecholamine release, which reached a plateau at about 36 min and amounted to 0.68 +/- 0.25 microgram 2 min-1 (n = 9). Such a secretory response was dramatically increased, and its shape modified, when glands were preperfused with K (17.7 mM)-Krebs: a peak of 3.77 +/- 0.42 micrograms 2 min-1 (n = 7) was reached at 18 min. This response was drastically reduced in the presence of nitrendipine (1 microM). 6. In summary, our results indicate that both [Na]0 reduction or Na accumulation into the chromaffin cell by inhibition of the Na pump with ouabain, greatly enhance the secretory efficacy of small increments of [K]0, and suggest that sodium may play a role in the regulation of catecholamine release mediated by voltage-dependent Ca channels in adrenal glands.

Adrenal Glands↗

Catecholamine release evoked by lithium from the perfused adrenal gland of the cat.

The effect of Li on catecholamine release by cat isolated retrogradely perfused adrenal gland was investigated. Replacement of Na (119 mM) by Li in the Krebs solution evoked a progressive increase in the spontaneous release of catecholamines that reached a maximum within 45 min and was Ca-dependent. This response was specific for Li, since sucrose or choline used as osmotic substitutes for Na, failed to increase the spontaneous release of catecholamines by the adrenal gland. In glands perfused with Li-Krebs for 30 min a sharp secretory response was observed when Li was replaced by sucrose or choline; no such an effect was seen when Li was replaced by Na. Partial replacement of Na by sucrose, in ouabain (10(-4) M, 10 min) pretreated glands perfused with normal Krebs induced a sharp increase in the catecholamine output whilst replacement by Li produced a significantly lower response. Reintroduction of Ca (2.5 mM, 2 min) in glands previously perfused with Ca-free, Mg-containing Li-Krebs, evoked a sharp increase in catecholamine release. No such an effect was seen when the glands were perfused with Ca-free normal, choline- or sucrose-Krebs. The release of catecholamines evoked by Ca reintroduction in glands previously perfused with Ca-free Li-Krebs was directly dependent on the Li concentration and the length of time of the Li loading period. In summary, our results indicate that Li accumulates in the cells and can partially substitute Na in the Na-Ca counter-transport system at the plasma membrane of the chromaffin cell.

Adrenal Glands↗