RESUMO
The measurement of circulating tumour markers (TMs) for the diagnosis or monitoring of breast cancer has sometimes been considered of limited utility. In addition to the overinterpretation of irrelevant changes in marker levels, the characteristics of the patient, the disease or other pathologies that can modify them are often not considered in their evaluation. On the other hand, there are recent data on the relationship of TMs with molecular subtypes and on their prognostic value, the knowledge of which may improve their clinical utility. This consensus article arises from a collaboration between the Spanish Society of Laboratory Medicine (SEQCML) and the Spanish Society of Medical Oncology (SEOM). It aims to improve the use and interpretation of circulating TMs in breast cancer. The text summarizes the current knowledge and available evidence on the subject and proposes a series of recommendations mainly focussed on the indication, the frequency of testing and the factors that should be considered for correctly interpreting changes in the levels of TMs.
Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Feminino , Testes Hematológicos/métodos , Testes Hematológicos/normas , HumanosRESUMO
Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involved with cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was to investigate whether the direct application of 10-9-10-5 M clobenzorex on isolated phenylephrine-precontracted rat aortic rings produces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-dependent vasorelaxant effect at the higher concentrations (10-7.5-10-5 M). The present outcome was not modified by 10-6 M atropine (an antagonist of muscarinic acetylcholine receptors), 3.1×10-7 M glibenclamide (an ATP-sensitive K+ channel blocker), 10-3 M 4-aminopyridine (4-AP; a voltage-activated K+ channel blocker), 10-5 M indomethacin (a prostaglandin synthesis inhibitor), 10-5 M clotrimazole (a cytochrome P450 inhibitor) or 10-5 M cycloheximide (a general protein synthesis inhibitor). Contrarily, the clobenzorex-induced vasorelaxation was significantly attenuated (P<0.05) by 10-5 M L-NAME (a direct inhibitor of nitric oxide synthase), 10-7 M ODQ (an inhibitor of nitric oxide-sensitive guanylyl cyclase), 10-6 M KT 5823 (an inhibitor of protein kinase G), 10-2 M TEA (a Ca2+-activated K+ channel blocker and non-specific voltage-activated K+ channel blocker) and 10-7 M apamin plus 10-7 M charybdotoxin (blockers of small- and large-conductance Ca2+-activated K+ channels, respectively), and was blocked by 8×10-2 M potassium (a high concentration) and removal of the vascular endothelium. These results suggest that the direct vasorelaxant effect by clobenzorex on phenylephrine-precontracted rat aortic rings involved stimulation of the NO/cGMP/PKG/Ca2+-activated K+ channel pathway.
Assuntos
Anfetaminas/farmacologia , Aorta Torácica/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Vasodilatação , Vasodilatadores/farmacologia , Animais , Canais de Cálcio/efeitos dos fármacos , Canais de Cálcio/metabolismo , Masculino , Óxido Nítrico Sintase Tipo III/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Canais de Potássio/efeitos dos fármacos , Canais de Potássio/metabolismo , Canais de Potássio de Abertura Dependente da Tensão da Membrana/efeitos dos fármacos , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Ratos , Ratos WistarRESUMO
Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involved with cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was to investigate whether the direct application of 10-9-10-5 M clobenzorex on isolated phenylephrine-precontracted rat aortic rings produces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-dependent vasorelaxant effect at the higher concentrations (10-7.5-10-5 M). The present outcome was not modified by 10-6 M atropine (an antagonist of muscarinic acetylcholine receptors), 3.1×10-7 M glibenclamide (an ATP-sensitive K+ channel blocker), 10-3 M 4-aminopyridine (4-AP; a voltage-activated K+ channel blocker), 10-5 M indomethacin (a prostaglandin synthesis inhibitor), 10-5 M clotrimazole (a cytochrome P450 inhibitor) or 10-5 M cycloheximide (a general protein synthesis inhibitor). Contrarily, the clobenzorex-induced vasorelaxation was significantly attenuated (P<0.05) by 10-5 M L-NAME (a direct inhibitor of nitric oxide synthase), 10-7 M ODQ (an inhibitor of nitric oxide-sensitive guanylyl cyclase), 10-6 M KT 5823 (an inhibitor of protein kinase G), 10-2 M TEA (a Ca2+-activated K+ channel blocker and non-specific voltage-activated K+ channel blocker) and 10-7 M apamin plus 10-7 M charybdotoxin (blockers of small- and large-conductance Ca2+-activated K+ channels, respectively), and was blocked by 8×10-2 M potassium (a high concentration) and removal of the vascular endothelium. These results suggest that the direct vasorelaxant effect by clobenzorex on phenylephrine-precontracted rat aortic rings involved stimulation of the NO/cGMP/PKG/Ca2+-activated K+ channel pathway.
Assuntos
Animais , Masculino , Ratos , Anfetaminas/farmacologia , Aorta Torácica/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Vasodilatação , Vasodilatadores/farmacologia , Canais de Cálcio/efeitos dos fármacos , Canais de Cálcio/metabolismo , Óxido Nítrico Sintase Tipo III/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Canais de Potássio de Abertura Dependente da Tensão da Membrana/efeitos dos fármacos , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Canais de Potássio/efeitos dos fármacos , Canais de Potássio/metabolismo , Ratos WistarRESUMO
Recently it has been suggested that the neurohormone prolactin (PRL) could act on the afferent nociceptive neurons. Indeed, PRL sensitizes transient receptor potential vanilloid 1 (TRPV1) channels present in nociceptive C-fibers and consequently reduces the pain threshold in a model of inflammatory pain. Accordingly, high plasma PRL levels in non-lactating females have been associated with several painful conditions (e.g. migraine). Paradoxically, an increase of PRL secretion during lactation induced a reduction in pain sensitivity. This difference could be attributed to the fact that PRL secreted from the adenopituitary (AP) is transformed into several molecular variants by the suckling stimulation. In order to test this hypothesis, the present study set out to investigate whether PRL from AP of suckled (S) or non-suckled (NS) lactating rats affects the activity of the male Wistar wide dynamic range (WDR) neurons. The WDR neurons are located in the dorsal horn of the spinal cord and receive input from the first-order neurons (Ab-, Ad- and C-fibers). Spinal administration of prolactin variant from NS rats (NS-PRL) or prolactin variant from S rats (S-PRL) had no effect on the neuronal activity of non-nociceptive Ab-fibers. However, the activities of nociceptive Ad-fibers and C-fibers were: (i) increased by NS-PRL and (ii) diminished by S-PRL. Either NS-PRL or S-PRL enhanced the post-discharge activity. Taken together, these results suggest that PRL from S or NS lactating rats could either facilitate or depress the nociceptive responses of spinal dorsal horn cells, depending on the physiological state of the rats.
Assuntos
Lactação/fisiologia , Fibras Nervosas/efeitos dos fármacos , Nociceptores/fisiologia , Células do Corno Posterior/fisiologia , Prolactina/farmacologia , Medula Espinal/citologia , Animais , Feminino , Lactação/sangue , Masculino , Fibras Nervosas/fisiologia , Nociceptores/efeitos dos fármacos , Limiar da Dor/efeitos dos fármacos , Limiar da Dor/fisiologia , Células do Corno Posterior/efeitos dos fármacos , Prolactina/sangue , Ratos , Ratos WistarRESUMO
Long-term potentiation (LTP) can be induced by electrical stimulation and gives rise to an increase in synaptic strength at the first relay. This phenomenon has been associated with learning and memory and also could be the origin of several pathological states elicited by an initial strong painful stimulus, such as some forms of neuropathic pain. We used high-frequency electrical stimulation of the sciatic nerve in anesthetized rats to produce spinal LTP. To evaluate the effect of spinal LTP on the activity of neurons in the posterior triangular nucleus of the thalamus (PoT), we applied an electrical stimulation (40 stimuli; 1ms; 0.5Hz; 1.5mA) to cutaneous tissues at 10-min intervals during at least 3h. In the majority of cases, PoT cells did not respond to cutaneous stimulation before LTP, but 50min after LTP induction PoT cells progressively began responding to the cutaneous stimulation. Furthermore, after 3h of LTP induction, PoT neurons could respond to cutaneous stimulation applied to different paws. Interestingly, the conduction velocities for the receptive field responses from the paw to the PoT cells were compatible with those of Aδ-fibers. Since PoT cells project to the insular cortex, the progressive increase in PoT activity and also the progressive unmasking of somatic receptive fields in response to LTP, place these cells in a key position to detect pain stimuli following central sensitization.
Assuntos
Potenciação de Longa Duração/fisiologia , Nociceptividade/fisiologia , Nervo Isquiático/fisiologia , Medula Espinal/fisiologia , Núcleos Talâmicos/fisiologia , Animais , Estimulação Elétrica , Masculino , Neurônios/fisiologia , Ratos , Fatores de TempoRESUMO
A DNA sequence homologous to a G alpha s DNA probe, and the corresponding G alpha s protein (stimulatory alpha-subunit of GTP-binding protein) were detected in Phycomyces blakesleeanus. The protein was demonstrated in membrane fractions of dormant spores of this fungus using three different experimental approaches. Photoaffinity-labelling experiments with [alpha-32P]GTP of the membrane fraction revealed two bands, of 56 and 32 kDa. The 56 kDa GTP-binding protein was detected by this method in all the stages of early development and growth investigated. Also, a spore protein of 56 kDa was ADP-ribosylated by cholera toxin, and a 56 kDa protein was detected by Western blotting with a specific antibody against mammalian G alpha s. These results indicate that G alpha s (56 kDa) is present in dormant spores of P. blakesleeanus. Using the ADP-ribosylation and Western blotting assays, G alpha s was detected during all stages of spore germination before the hyphae became highly branched, but it was not detected in the branched hyphae that formed 18 h after the initiation of spore germination. Therefore, G alpha s is expressed differentially during Phycomyces development.
Assuntos
Proteínas de Ligação ao GTP/metabolismo , Phycomyces/fisiologia , Adenosina Difosfato Ribose/metabolismo , Marcadores de Afinidade , Toxina da Cólera/farmacologia , DNA Fúngico/genética , Proteínas de Ligação ao GTP/química , Proteínas de Ligação ao GTP/genética , Regulação da Expressão Gênica no Desenvolvimento , Regulação Fúngica da Expressão Gênica , Genes Fúngicos , Guanosina Trifosfato , Phycomyces/genética , Phycomyces/crescimento & desenvolvimento , Esporos Fúngicos/genética , Esporos Fúngicos/fisiologiaRESUMO
Thirty nine patients with hydatiform mole with clinical, echosonographic and hormonal diagnosis, were analyzed, from March, 1991 to February 1993 at the Nuevo Hospital Civil de Guadalajara. Incidence was I out of 301 pregnancies; average age, 24.6 years; 35.8% were primigravidae; average amenorreha was 15.6 weeks and there were not complications in 84.6%. The most frequent symptoms were transvaginal bleeding, 92.3%; mole rests expulsion, 25.6% and hyperemesis, 23%. The uterine fundus was larger in 17 patients; smaller in 13; the same in 5 and there were no data for four cases. An uterine curettage was performed in 38 patients; there was hysterotomy performed also for important bleeding; and there were 11 patients transfused. The histopathologic results of hydatidiform mole were confirmed in 84.6%. Only 20% of the patients came back for a post-evacuation control treatment. These results suggest that the characteristics of mola pregnancy at the Nuevo Hospital Civil de Guadalajara are similar to what has been reported in the literature; with a delayed diagnosis and a poor follow up of cases.
Assuntos
Mola Hidatiforme/epidemiologia , Neoplasias Uterinas/epidemiologia , Adulto , Dilatação e Curetagem , Feminino , Humanos , Mola Hidatiforme/diagnóstico por imagem , Mola Hidatiforme/patologia , Mola Hidatiforme/cirurgia , Incidência , México/epidemiologia , Paridade , Gravidez , Ultrassonografia Pré-Natal , Hemorragia Uterina/etiologia , Neoplasias Uterinas/diagnóstico por imagem , Neoplasias Uterinas/patologia , Neoplasias Uterinas/cirurgia , Útero/patologia , Útero/cirurgiaRESUMO
Anopheles pseudopunctipennis showed a bimodal daily pattern in flight activity with the largest peak at 2000 h and the smaller one at 0400 h. In the first 10 days as adults, the maximum swarming activity was observed between 2-6 days of age. Also, sexual encounters were registered at the same time interval.
Assuntos
Anopheles/fisiologia , Voo Animal , Comportamento Sexual Animal , Animais , Feminino , Masculino , MéxicoRESUMO
PIP: Puberty today occurs about 2 years earlier than it did at the beginning of the century. The age of menarche is now usually between 11-13 years, while the establishment of spermatogenesis and appearance of the 1st ejaculation usually occurs between 13-15 years. The ages at which adolescents feel mature, want to behave like adults, and initiate sexual activity are now lower than in the past. Sexual relations may occur between adolescents before they are fully capable of recognizing their consequences as autonomous and responsible acts guided by a system of moral convictions. Both marriage and parenthood may have unfavorable consequences for future personality development, sexual adjustment, and the personal-social adaptation of the individual. In Cuba, the persistence of traces of bourgeois mentality can be seen in the tendency to teach young girls false concepts of female behavior. Traits such as submissiveness, passivity, and fragility are stressed, and girls are taught to inhibit their sexuality from a very young age. Adolescent boys are expected to display virility and machismo. Adolescent boys may be so interested in the physical aspects of sexual activity that they deprecate the aspects, considering them to be weak female traits. Boys are more likely to separate the sexual object and the love object, while such duality is unusual in girls. Among the most serious problems of adolescent sexual activity in Cuba is a high rate of abortions among young adolescents. Some adolescents are promiscuous and have frequent changes of partner. The age group 15-19 years has the 3rd highest rate of syphilis and the 2nd highest of gonorrhea. The proportion of births to minors has increased from 22% in 1973 to almost half in some provinces. Divorce rates have been in constant increase in Cuba, and psychosocial immaturity of very young spouses is a principal factor in divorce. The widening temporal gap between attainment of puberty and marriage, which is likely to be postponed until the completion of ever more time-consuming educations, is a factor in increased premarital sex although it is not a determinant of it. An adequate sex education program would help adolescents develop responsible attitudes and good foundations for their future sexual adjustments. It would also help prevent adolescent pregnancy, with its frequent negative consequences.^ieng