Uso de ciclofosfamida endovenosa en nefritis lúpica / Cyclophosphamide used in the lupus nephritis

Evaluamos en forma prospectiva el efecto de la ciclofosfamida (CF) endovenosa en 20 niños (11 hembras y 9 varones) con criterios clínicos de glomerulonefritis (GN) lúpica moderada a severa. A todos se les realizó biopsia renal y última clasificación según OMS². Se indicó CF endovenosa a dosis de 500 a 750 mg/m² mensualmente durante un tiempo promedio de 8 meses y posteriormente trimestral por 18 meses, conjuntamente se indicó prednisona a 2 mg/kg/día durante el primer mes con disminución de la dosis a 0,25 mg/kg/día. Se apreció caída significativa de proteinuria (67 a 34 mg/h/m²), no hubo variación importante en los valores de depuración de creatinina inicial y final. Concluimos que la CF endovenosa es un tratamiento efectivo en casos de nefritis lúpica severa. Sin embargo, debemos tomar en cuenta los potenciales riesgos de su uso

Improved behavioral performance of rats after pre- and postnatal administration of vasopressin.

In two separate and independent experimental series it was studied, whether 8-arginine-vasopressin (AVP) or 8-lysine-vasopressin (LVP) administered daily in microgram amounts to pregnant rats, and/or to their offspring postnatally for 30 days, induce alterations that can be registered by a behavioral test. The realization of the test used, a foot-shock motivated brightness discrimination (BD) reaction, includes learning and memory processes. There is one general result of the two experimental series, which include 263 rats divided up in different combinations of pretreatment. Vasopressin (VP), AVP or LVP, pre- and postnatally administered, induces a significantly improved BD performance of approximately 40%, compared to the control groups. The improvement is detectable in different ages of the offspring, in females as well as in males. A smaller though also significant improvement was observed when AVP or LVP was injected only postnatally. The critical period in which the peptides are able to induce the alterations measured probably includes prenatal and postnatal periods in the lives of the rats. What molecular interactions actually underly the improved behavioral performance remain to be clarified.

Role of prostaglandin release in the response of tight epithelia to Ca2+ ionophores.

We have studied the effects of the Ca2+ ionophores A23187 and ionomycin on ion transport across amphibian skin and urinary bladder. Both A23187 and ionomycin stimulated transepithelial Na+ transport across the skin. Ionomycin also markedly increased the conductance of an amiloride-insensitive pathway. Both ionophores markedly stimulated the release of prostaglandin E2 (PGE2) into the solution bathing the serosal surface of the skin. Addition of indomethacin to the serosal bathing solution of the skin blocked both the stimulation of short-circuit current (Isc) and the release of prostaglandin caused by the ionophores. Acetylsalicylic acid also blocked the ionomycin-induced stimulation of Isc. These results suggest that the stimulation of Na+ transport caused by Ca2+ ionophores is mediated by the release of a product of the cyclooxygenase pathway, very likely PGE2. Ca2+ ionophores also stimulated the release of PGE2 in urinary bladders; however, they generally depressed Isc. Since the effect on Isc caused by the addition of exogenous PGE2 was different in urinary bladders than in skins, we suggest that at least part of the difference in the action of ionophores is due to the difference in the sensitivity of these epithelia to PGE2. Our results suggest that the heterogeneity of effects that Ca2+ ionophores cause in the physiological parameters of tight epithelia are not always the direct result of increased cytoplasmic Ca2+ but that they may be mediated by other tissue responses triggered by the addition of the ionophores.

Immuno-electron-microscopic analysis of the basal route of secretion in the subcommissural organ of the rabbit.

Low-temperature-embedded tissue of the subcommissural organ (SCO) of the rabbit was analyzed for the basal route of secretory product by means of indirect immuno-metal cytochemistry (protein A-gold technique) at the electron-microscopic level. By use of (1) an antiserum against bovine Reissner's fibre (see Sterba et al. 1981) and, thereafter, (2) particulate gold-marker solution, immunoreactive sites could be clearly visualized within the extracellular matrix of both (a) the basal part of the ependymal cell layer, and (b) the hypendyma proper. Abundant secretory material was identified within (i) dilated intercellular spaces (a + b) as well as (ii) branching basal lamina labyrinths and distinct perivascular spaces (b). All these compartments are thought to belong to a system of extracellular channels, which may function in secretion directed toward hypendymal blood vessels.

[Somatostatin in lamprey brains (Lampetra planeri Bloch)]. / Somatostatin im Gehirn des Bachneunauges (Lampetra planeri Bloch).

In the brain of larval and adult lampreys (Lampetra planeri Bloch) a distinct somatostatin system using somatostatin antiserum with the unlabeled peroxidase-antiperoxidase technique was demonstrated. The immune reactive perikarya are localized in the nucleus ventralis hypothalami and they are restricted to this nucleus without exception. A small number of immune positive efferences invades the commissura praeinfundibularis. In the neurohypophysis localized caudally from this commissure and in the adenohypophysis no somatostatin fibres could be visualized. Most of the efferences leave the hypothalamus as exohypothalamic fibres and form a system of somatostatin fibres which extends from the telencephalon to the medulla oblongata. Regionally, this system is organized in a net-like manner.

Preparation and discharge of secretion in the subcommissural organ of the rat. An electron-microscopic immunocytochemical study.

The secretion of the subcommissural organ (SCO) of the rat was studied by means of immunocytochemistry at the electron-microscopic level with the use of (1) the polar embedding medium Lowicryl K4M at -30 degrees C, (2) the protein A-gold technique, and (3) a rabbit antiserum against bovine Reissner's fiber (see Sterba et al. 1981). Two different substructures of the ependymal and the hypendymal SCO-cells display a positive immunocytochemical reaction: (1) sacs containing flocculent secretion, which originate from the granular endoplasmic reticulum, and (2) vacuoles filled with fine granular secretion, which are pinched off from the Golgi apparatus. The secretory material of the sacs and the vacuoles is discharged both (i) apically into the cerebrospinal fluid and (ii) basally into intercellular spaces of the SCO-hypendyma. The apically released secretion is condensed to a lamina-like formation, which more caudally assumes the form of Reissner's fiber. The route of the basally released secretion remains, however, vague. The "periodically striated bodies", which were thought to be morphological mediators of the discharge of the secretion into the capillaries, are never labeled by gold particles.

Spectrophotometric analyses of hydroxysteroid dehydrogenase activity in presumed steroid-producing tissues of the brook lamprey (Lampetra planeri bloch) in different developmental stages.

Hydroxysteroid dehydrogenase (HSD) activity was determined spectrophotometrically on homogenates of the pronephros, the opisthonephros, and the gonads of metamorphosing, immature, and mature adult male and female brook lampreys (Lampetra planeri Bloch), employing pregnenolone, dehydroepiandrosterone, androsterone, epiandrosterone, and 3 beta,17 beta-dihydroxy-5 alpha-androstane as substrates and NAD or NADP as coenzymes in October, December, February, and April. With NADP a higher HSD-dependent HSD activity was detected in presumed adrenocortical tissue (PAT) homogenates with pregnenolone and 3 beta,17 beta-dihydroxy-5 alpha-androstane and in gonad homogenates only with 3 beta,17 beta-dihydroxy-5 alpha-androstane. With 3 beta,17 beta-dihydroxy-5 alpha-androstane as substrate the highest enzyme activities were measured in PAT and gonad homogenates from animals of all investigated life stages. A varying intensity of HSD activity in the examined tissue homogenates probably dependent on stages of the individual development was observed.

[Immunocytochemical demonstration of neuropeptides (neurophysin and oxytocin) by the protein A-gold technic]. / Immuncytochemische Darstellung von Neuropeptiden (Neurophysin und Oxytocin) mit der Protein-A-Gold-Technik.

In the classic peptidergic neurosecretory system of vertebrates the neurohormone oxytocin is associated with the carrier protein neurophysin. By using small gold particles (3 to 12 nm) in the protein A-gold technique, both the hormone and the carrier-protein will be labelled, while larger particles (20 nm) label only the neurophysin. To bind the latter particles, a greater number of Fc-regions of antigen-IgG-complexes seems to be necessary.

Immunocytochemical investigation of the subcommissural organ in the rat.

The results of a preliminary immunocytochemical investigation on the subcommissural organ (SCO) in rats show that (1) Reissner's fiber (RF) or essential compounds of the RF are produced by the SCO, (2) the immunoreactive material is produced in the epithelial cells of the SCO as well as in the hypendymal cells, and (3) the immunoreactive material of the SCO belongs to a category of endogenous peptides to date not demonstrable immunocytochemically in other brain structures.

Extrahypothalamic peptidergic neurosecretion. II. Neurosecretion in the subfornical organ of Rana esculenta L.

In the subfornical organ of Rana esculenta, three basic structural elements can be demonstrated by light microscopic and immunohistological techniques used for the demonstration of products of the neurosecretory system. These elements are: (i) neurones and their processes, which the constituents of the subfornical organ proper, (ii) afferent axons of the preoptic nucleus, and (iii) subependymal cells with coarse processes. The vesicular inclusions of the two former structures correspond to the neurophysin vesicles with respect to their size, structure and reactivity. The vesicles of the subependymal cells belong to the same size class, possess a somewhat granular internal structure and react atypically after the application of the ultrahistochemical technique for the identification of neurophysin vesicles. Presumably, their content is a glycoprotein with a high proportion of cystine. The peptidergic axons of the preoptic nucleus projecting to the subfornical organ form neuroneuronal synapses.

The clinical significance of Raynaud's phenomenon in systemic lupus erythematosus.

In a prospective study of 226 patients with systemic lupus erythematosus (SLE), 91 patients (40%) had Raynaud's phenomenon. These patients were compared to 135 patients without Raynaud's phenomenon. Patients with Raynaud's phenomenon had a greater incidence of arthritis (P less than 0.02), malar rash (P less than 0.003), and photosensitivity (P less than 0.03), and a lesser incidence of severe renal disease as manifested by serum creatinine over 3.0 mg/dl (P less than 0.007) or creatinine clearance below 60 ml/minute. Patients with Raynaud's phenomenon were less likely to have severe, life threatening disease and received a lower average monthly (P less than 0.01) and a lower peak daily corticosteroid dose (P less than 0.01). Fourteen patients (16%) with Raynaud's phenomenon died, compared to 41 without (30%) (P less than 0.03). Raynaud's phenomenon in patients with SLE is associated with milder disease and may be regarded as a favorable prognostic sign.

Peptide containing vesicles within neuro-neuronal synapses.

In the descending part of the classical neurosecretory system, the axon terminals are not differentiated or they take the form of presynaptic elements which then form synaptoids or synapses with pituicytes or adenohypophyseal glandular cells respectively. In contrast, the axon terminals of the ascending part fulfil the criteria of true presynaptic elements which form synapses with other neurones. The presence of neurophysin vesicles in the presynaptic element is a particular morphologic feature of these neuro-neuronal synapses.

The reticular formation of lampreys (Petromyzonidae)--a target area for exohypothalamic vasotocinergic fibres.

The octapeptide vasotocin, which is formed in the classical neurosecretory nuclei of lampreys (Petromyzonidae), is transported, bound to the carrier protein neurophysin, not only to the neurohypophysis but also to various other regions of the brain via exohypothalamic fibres. A target area of this exohypothalamic vasotocinergic system is, in the brook lamprey (Lampetra planeri Bloch), a relatively well circumscribed area in the isthmus region of the rhombencephalic tegmentum motoricum, which is called area lateralis tegmenti. In this area, which belongs to the reticular formation, the vasotocinergic fibres form synaptic contacts with nerve cell perikarya and processes. The vesicles contained in the fibres were identified, ultrahistochemically, as neurophysin vesicles. They correspond to the neurophysin vesicles observed in the neurohypophysis of the same species. The functional significance of the vasotocinergic supply to portions of the reticular formation in lampreys is open to discussion.