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Biomedical subjects

A Morales

Publications and source records attributed to A Morales.

At least 37 records · Page 2Linked to original sources
PubMed2003

Swimming of pregnant rats at different water temperatures.

We studied the chronic effect of exercise during water immersion, associated with thermal stress (water temperature at 22, 35 and 40 degrees C) at an intensity of 80% of maximal work load supported in pregnant rats (P) and non-pregnant female rats (NP). P and NP were subdivided into three subgroups according to water temperature during exercise (P22 and NP22; P35 and NP35; P40 and NP40). The animals were submitted to daily swimming sessions of 10-15 min, for 19 days of pregnancy (P) or experimental conditions (NP). Plasma concentration of triglycerides, cholesterol, glucose, total protein, albumin and corticosterone were determined 24 h after the last exercise session. Weight gain and rectal temperature pre- and post-swimming session were also determined. The offspring were examined just after caesarian section on the 20th day of pregnancy to check weight, length and litter size. Pregnant rats showed an increase of triglycerides, reduction of glycemia, total protein and albumin and cholesterol (at 35 degrees C) when compared to non-pregnant animals. Such effects probably lead to an adequate delivery of substrate to the fetus and prepare the mother for lactation. Daily thermal stress did not modify metabolic responses to exercise in pregnant rats. Results also show a deleterious effect on offspring when the mother is exposed daily to extreme temperatures during swimming. These results suggest that water temperature (cold and hot) in swimming have to be considered to avoid damage in fetal development.

Animals↗
PubMed2003

Topical lidocaine-prilocaine spray for the treatment of premature ejaculation: a proof of concept study.

Premature ejaculation (PE) is the most common sexual dysfunction in men. Since heightened sensitivity of the glans is implicated in PE, it seems reasonable that reducing this sensitivity could have a delaying effect on intravaginal ejaculation latency time (IVELT) without adversely affecting the sensation of ejaculation. We have developed a local anesthetic combination, in a metered-dose aerosol delivery system, that delivers lidocaine and prilocaine in base form without organic solvents. The drug can be easily removed prior to vaginal penetration, circumventing the need for a condom that most patients find undesirable. Herein, we report on a prospective open-label pilot study investigating the safety and efficacy of this novel delivery system for topical local anesthetic to the glans penis aimed at prolonging the IVELT in patients who self-reported having PE. This was an open-label prospective pilot study. The lidocaine-prilocaine (LP) aerosol delivered 7.5 mg lidocaine and 2.5 mg prilocaine, both in base form, per actuation. A total of 14 men who had been referred to urology clinics with the problem of PE were recruited. Consent was obtained from both subjects and their partners. Couples were asked to time their IVELT without treatment on one encounter, and then on five subsequent encounters were asked to apply the spray to the glans penis, leave on for 10-15 min, wipe off carefully before intercourse. The IVELT was timed with a stopwatch and then both partners were asked to rate their individual satisfaction relative to baseline without treatment. They were also asked to document any adverse events or comments. In all, 11 patients completed the study. The average IVELT increased from 1 min:24 s to 11 min:21 s (P=0.008) representing an average eight-fold increase. No subjects experienced a decrease in IVELT. The average satisfaction score for both subjects and partners was 1.0; on a scale where -1 was worse, 0 the same, +1 better and +2 much better. Topical LP spray, applied to the glans penis 15 min before intercourse, prolongs ejaculation time significantly and improves sexual satisfaction in both men with PE and their partners. The glandular numbness, noticed in only two cases, did not adversely affect the quality of the orgasm. Occasionally, a patient reported difficulty maintaining an erection while waiting the required 15 min between application of the spray and the initiation of intercourse.

Administration, Topical↗
PubMed2003

Hypogonadism and erectile dysfunction: pathophysiological observations and therapeutic outcomes.

Androgens have a profound effect in male sexual function in general and erectile physiology in particular. Despite the common belief that male sexuality is fully dependent on normal androgens, hypogonadal men are capable of sexual erections; almost a third of men receiving effective antiandrogen therapy can develop erections when tested with an erotic challenge. However, successful hormonal supplementation that results in normal testosterone values does not always restore libido and erectile function. Although the primary goal of treatment for hypogonadism may be to restore sexual function, there will be other significant benefits and potential drawbacks. Libido, general well-being, osteoporosis, muscle strength, mental acuity, and growth hormone levels will all be positively affected by appropriate management of low testosterone levels. Testosterone replacement therapy should maintain not only physiological levels of serum testosterone but also its metabolites, including dihydrotestosterone and oestradiol. The assessment of hypogonadism, its treatment and monitoring, are unavoidable responsibilities of the urologist.

Androgens↗
PubMed2003

An ICI 182,780-sensitive, membrane-related estrogen receptor contributes to estrogenic neuroprotective actions against amyloid-beta toxicity.

Although estrogen (E2)-related neuroprotection has been repeatedly demonstrated in different models, the involvement of non-classical estrogen receptors (ERs) in this activity remains unclear. Using SN56 murine cholinergic cell line from the basal forebrain, we present evidence indicating that an ER associated with the plasma membrane participates in estrogen-dependent reduction of neuronal death induced by amyloid-beta peptide (Abeta) toxicity. Exposure to either E2 or estradiol-horseradish peroxidase (E-HRP) for 15 min significantly reduced Abeta-induced cell death. This effect was decreased by the ER antagonist ICI 182,780 as well as by MC-20 antibody directed to a region neighboring the ligand-binding domain of ERa. Using MC-20 antibody in unpermeabilized SN56 cells, we detected a protein at the plasma membrane region. The binding of impermeant forms of E2, E-HRP, and E-BSA-FITC to specific sites of SN56 plasma membrane was blocked by pre-incubation with E2, ICI 182,780, and MC-20 antibody in a concentration-dependent manner. Thus, a membrane-related ER that shares some structural homologies with ERalpha may participate in estrogen-mediated neuroprotection.

Amyloid beta-Peptides↗
PubMed2003

Effect of ham protein substitution on oxidative stress in older adults.

Mediterranean diet has been related to a low risk of coronary hearth disease. In the present study, we have evaluated the effect of substituting 120 g of meat by 120 g of acorn-fed Iberian ham (one of the meat components of the Mediterranean diet) on body weight, blood pressure (MAP), plasma lipids and oxidant-antioxidant equilibrium in 13 males and 8 females with an average age of 71. Study was performed in three periods: basal diet evaluations (BD1), ham diet for 6 weeks (HD), and basal diet again for 6 weeks (BD2). MAP significantly diminished from 96 mmHg in BD1 to 89 mmHg after HD. After BD2, MAP remained in the same value. Plasma total antioxidant substances increased from 0.791 mmol/L in BD1, to 1.525 in HD, and to 1.213 in BD2. Glutathione reductase significantly increased from 49.5 U/L in BD1 to 57 in HD and decreased to 49.2 in BD2. Glutathione peroxidase rose from 33 U/gHb in BD1 to 72 in HD and decreased to 52 in BD2. Superoxide dismutase increased from 401 U/gHb in BD1 to 723 in HD and decreased to 433 in BD2. Plasma thiobarbituric acid reacting substances (TBARS) fall from 1.65 mmol/l in BD1 to 1.38 in HD and to 1.47 in BD2. TBARS in erythrocyte membranes also diminished but only in BD2. It can be concluded that including acorn-fed Iberian ham in the diet increased the antioxidant substances and decrease lipid peroxidation, with its subsequent beneficial effects on the atherogenic risk factors.

Aged↗
PubMed2002

Functional transplantation of chloride channels from the human syncytiotrophoblast microvillous membrane to Xenopus oocytes.

The materno-fetal transfer of metabolites and nutrients requires the operation of specific transport mechanisms through syncytiotrophoblast membranes. Electrophysiological studies on these cells are scarce and, because of their syncytial nature, whole-cell current recordings have not been carried out. We have now studied whether or not ion channels from the human syncytiotrophoblast microvillous (hSM) membrane can be transplanted to Xenopus oocytes. Sixty-two percent of hSM-injected oocytes displayed lower resting potential and higher membrane conductance than uninjected cells. The increased membrane conductance was due to the incorporation of Cl(-) channels, because neither replacing Na(+) in the bathing solution by N-methyl- D-glucamine or K(+), nor withdrawing Ca(2+) had any significant effect on the currents elicited by voltage pulses. In contrast, substitution of Cl(-) by different anions markedly affected the membrane conductance, giving an anion selectivity sequence of I(-)>Br(-)>Cl(-)>methanosulfonate congruent with gluconate. In addition, disulfonic stilbenes and gluconate, but not anthracene-9-carboxylic acid, blocked the transplanted channels. These properties are compatible with those of placental Cl(-) "maxi" channels. It is concluded that functional Cl(-) channels from the hSM become effectively incorporated into the Xenopus oocyte membrane, where their function can be studied in detail.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2002

Protein orientation affects the efficiency of functional protein transplantation into the xenopus oocyte membrane.

Xenopus oocytes incorporate into their plasma membrane nicotinic acetylcholine receptors (nAChRs) after intracellular injection of lipid vesicles bearing this protein. The advantage of this approach over the classical oocyte expression system lies in the transplantation of native, fully processed proteins, although the efficiency of functional incorporation of nAChRs is low. We have now studied the incorporation into the oocyte membrane of the Torpedo chloride channel (ClC-0), a minor contaminant protein in some nAChR preparations. nAChR-injected oocytes incorporated functional ClC-0: i) in a higher number than functional nAChRs; ii) retaining their original properties; and iii) with a right-side-out orientation in the oocyte membrane. In an attempt to elucidate the reasons for the low efficiency in the functional incorporation of nAChRs into the oocyte membrane, we combined electrophysiological and [125I]alpha-bungarotoxin-binding experiments. Up to 3% of injected nAChRs were present in the oocyte plasma membrane at a given time. Thus, fusion of lipoproteosome vesicles to the oocyte plasma membrane is not the limiting factor for an efficient functional transplantation of foreign proteins. Accounting for the low rate of functional transplantation of nAChRs is their backward orientation in the oocyte membrane, since about 80% of them adopted an out-side-in orientation. Other factors, including differences in the susceptibility of the transplanted proteins to intracellular damage should also be considered.

Animals↗
PubMed2002

Compressional and torsional wave amplitudes in rods with periodic structures.

To measure and detect elastic waves in metallic rods a low-frequency electromagnetic-acoustic transducer has been developed. Frequencies range from a few hertz up to hundreds of kilohertz. With appropriate configuration of the transducer, compressional or torsional waves can be selectively excited or detected. Although the transducer can be used in many different situations, it has been tested and applied to a locally periodic rod, which consists of a finite number of unit cells. The measured wave amplitudes are compared with theoretical ones, obtained with the one-dimensional transfer matrix method, and excellent agreement is obtained.

Journal Article↗
PubMed2001

jkk-1 and mek-1 regulate body movement coordination and response to heavy metals through jnk-1 in Caenorhabditis elegans.

Although in vitro evidence suggests two c-Jun N-terminal kinase (JNK) kinases, MKK4 and MKK7, transactivate JNK, in vivo confirmation is incomplete. In fact, JNK deficiency may differ from the composite deficiency of MKK4 and MKK7 in Drosophila and mice. Recently, the Caenorhabditis elegans homolog of human JNK, jnk-1, and two MKK-7s, mek-1 and jkk-1, were cloned. Here we characterize jnk-1, which encodes two isoforms JNK-1 alpha and JNK-1 beta. A null allele, jnk-1(gk7), yielded worms with defective body movement coordination and modest mechanosensory deficits. Similarly to jkk-1 mutants, elimination of GABAergic signals suppressed the jnk-1(gk7) locomotion defect. Like mek-1 nulls, jnk-1(gk7) showed copper and cadmium hypersensitivity. Conditional expression of JNK-1 isoforms rescued these defects, suggesting that they are not due to developmental errors. While jkk-1 or mek-1 inactivation mimicked jnk-1(gk7) locomotion and heavy metal stress defects, respectively, mkk-4 inactivation did not, but rather yielded defective egg laying. Our results delineate at least two different JNK pathways through jkk-1 and mek-1 in C.elegans, and define interaction between MKK7, but not MKK4, and JNK.

Alternative Splicing↗
PubMed2001

Estrogen modulates norepinephrine-induced accumulation of adenosine cyclic monophosphate in a subpopulation of immortalized luteinizing hormone-releasing hormone secreting neurons from the mouse hypothalamus.

A subpopulation of luteinizing hormone-releasing hormone (LHRH)-producing cells that express the intermediate filament protein vimentin and the neuronal marker neurofilament 145, but not neurofilament 200 nor glial fibrillary acidic protein, has been isolated from GT1-7 cultures. These cells express the mRNA encoding estrogen receptor alpha (ERalpha) and respond to physiological concentrations of 17beta-estradiol (E2) by reducing the accumulation of cyclic adenosine monophosphate induced by norepinephrine, but not that induced by direct activation of adenylate cyclase. These results indicate that the activity of LHRH-producing neurons may be directly modulated by estrogen. In addition, they are suggestive of an estrogen-dependent desensitization of the beta-adrenoceptor in these cells.

Animals↗
PubMed2001

Cell autonomous apoptosis defects in acid sphingomyelinase knockout fibroblasts.

A body of evidence suggests that stress-induced sphingomyelin hydrolysis to the second messenger ceramide initiates apoptosis in some cells. Although studies using lymphoblasts from Niemann-Pick disease patients or acid sphingomyelinase (ASMase)-deficient mice have provided genetic support for this hypothesis, these models have not been universally accepted as definitive. Here, we show that mouse embryonic fibroblasts (MEFs) prepared from asmase mice manifest cell autonomous defects in apoptosis in response to several stresses. In particular, asmase(-/-) MEFs failed to generate ceramide and were totally resistant to radiation-induced apoptosis but remained sensitive to staurosporine, which did not induce ceramide. asmase(-/-) MEFs were also partially resistant to tumor necrosis factor alpha/ actinomycin D and serum withdrawal. Thus, resistance to apoptosis in asmase(-/-) MEFs was not global but rather stress type specific. Most importantly, the sensitivity to stress could be restored in the asmase(-/-) MEFs by administration of natural ceramide. Overcoming apoptosis resistance by natural ceramide is evidence that it is the lack of ceramide, not ASMase, that determines apoptosis sensitivity. The ability to rescue the apoptotic phenotype without reversing the genotype by the product of the enzymatic deficiency provides proof that ceramide is obligate for apoptosis induction in response to some stresses.

Animals↗
PubMed2001

Yohimbine in erectile dysfunction: would an orphan drug ever be properly assessed?

The systemic use of adrenergic antagonists in the treatment of sexual dysfunction has originated more controversy than results. Among the various agents, yohimbine has acquired an unenviable reputation in the treatment of erectile dysfunction. The drug is pharmacologically well characterized as an alpha2 adrenoceptor antagonist with activity in the central and peripheral nervous systems. In-depth, systematic studies in animals have shown that yohimbine has a remarkable positive effect on sexual performance. Meta-analyses of the few controlled, randomized human studies have consistently shown an advantage of yohimbine over placebo. Despite such a long history and encouraging activity, the drug has not yet been subjected to scientifically rigid human clinical trials. Although relevant basic pharmacological and animal research information has been available for over 15 years, recent studies have been designed with a lack of insight and complete disregard of those fundamental studies. Currently, dose-response investigations are not available, alternative routes of administration (i.e., sublingual) have not been investigated, nor has continuous versus "on-demand" administration been explored. Synergistic activity with other drugs was last studied nearly four decades ago. Assessments of various populations were carried out in very limited cohorts and only in the most general terms. In short, properly designed trials in humans have not been performed. This apparent lack of scientific and financial interest has various roots. First of all, yohimbine is an old drug. As such it does not enjoy patent protection or commercial viability. Until molecular/formulation changes can be brought about (as recently happened with two other venerable agents: phentolamine and apomorphine) serious investigation of the drug will remain in limbo. Another promising avenue is the potential for synergistic effect of yohimbine with other compounds. When all is said and done, it could be that the naysayers are right and yohimbine indeed lacks clinical activity as a treatment for the phallodynamically challenged. As long as it remains an orphan drug we will never know. One hopes that interest can be eventually generated for the proper assessment of yohimbine in a different formulation or in combination with other agents.

Adrenergic alpha-Antagonists↗
PubMed2001

Hormonal erectile dysfunction. Evaluation and management.

The clinical diagnosis of hypogonadism in the adult is difficult to establish on the basis of a history and physical examination and universally requires biochemical investigations. A serum testosterone determination is justified in men complaining of erectile dysfunction with or without alterations in sexual desire. Among the causes of erectile dysfunction, hypotestosteronemia rates are low. The prevalence of erectile dysfunction particularly is common at a period in life when alterations occur in male hormonal environment. The treatment of hypogonadal erectile dysfunction, regardless of age, is readily available, safe, and effective. The positive impact of treatment on the overall quality of life can be significant. The presence of erectile dysfunction in an aging man (> 55 years) does not imply the presence of hypogonadism, and, even if the two conditions are present, the indications for treatment require good clinical judgment. Persistent low testosterone levels may have significant detrimental effects in other organ systems; therefore, a timely diagnosis of androgen deficiency and appropriate treatment may have significant effects outside the narrow field of sexual performance.

Administration, Cutaneous↗