Effects of amino acids on the excitability of respiratory bulbospinal neurons in solitary and para-ambigual regions of medulla in cat

The effects of inhibitory (gamma-aminobutyric acid (GABA) and glycine) and excitatory (L-glutamate and DL-homocysteate, DLH) amino acids on the excitability of respiratory bulbospinal neurons were studied in decerebrate, paralyzed, bilaterally vagotomized, artificially ventilated cats. Unit activities were recorded extracellularly in the medulla in both the ventrolateral portion of the nucleus tractus solitarius and the para-ambigual region in the vicinity of the nucleus ambiguus (dorsal and ventral respiratory groups, respectively). All neurons were bulbospinal since they could be antidromically activated by electrical stimuli to the spinal cord. We used variations in antidromic latency (ADL) as a measure of changes in excitability of the soma. All neurons exhibited variations in ADL related to the respiratory cycle, being shortest (minimum ADL) during neural activity and longest (maximum ADL) in the silent period. Neurons whose discharge frequencies fell during application of putative inhibitory amino acids showed an increase of minimum ADL compared to control, indicating hyperpolarization. Minimum ADL, in some cells, became shorter during application of excitatory amino acids, indicating depolarization; in others, mechanisms secondary to increased neuronal firing likely obscured their effects. The transient maximum ADL usually present at the onset of the silent period was increased by excitatory amino acids and, in some units, was reduced or eliminated by inhibitory amino acids. These effects are discussed in terms of a modulation by synaptic inputs and neurotransmitters of the cumulative afterhyperpolarization which follows bursts of action potentials.     

Small urothelial carcinoma: diagnosis and treatment by cold forceps biopsy

From 1987 to 1988 we used cold biopsy forceps to remove completely 92 urothelial neoplasms ranging from 0.3 to 3 mm. Rigid biopsy forceps were used. The urologist usually treats these bladder neoplasms by diathermy coagulation, which obviously makes histological study impossible. On the other hand, due to the small size of these lesions even removal with the cutting loop inevitably causes deep regressive modifications that prevent accurate morphological evaluation. Histological examination of the neoplasms removed revealed the presence of low to medium grade (stage Ta, grades 1 to 2) noninfiltrating papillary carcinoma in 75 cases, high grade (stage Ta, grade 3) noninfiltrating papillary carcinoma in 9 and medium to high grade (stage T1, grades 2 to 3) infiltrating papillary carcinoma in 8, 1 of which had areas of squamous cell carcinoma. This method enabled us to study the morphology of the urothelial lesions in the initial phase. In our study population the number of high grade lesions and/or lesions with early signs of infiltration (17 of 92) appears to be noteworthy despite the small size of the tumors.     

Transsynaptic degeneration of lateral geniculate bodies in blind children: in vivo MR demonstration.

PURPOSETo investigate signal alterations in the thalamic lateral geniculate bodies of blind patients compatible with transsynaptic degeneration of these nuclei caused by pregeniculate or postgeniculate interruption of the visual pathway.METHODSSix patients were selected from a group of blind children in our care. Four had cerebral palsy caused by periventricular leukomalacia, one had infantile neuroaxonal dystrophy, and one had Chiari I malformation and hydrocephalus, which was worsened by bilateral ischemic lesions of the occipital lobes. MR examinations (obtained at 0.5 T) were reviewed retrospectively by two neuroradiologists, with particular attention to the visual pathway.RESULTSSymmetric, focal areas of T2 prolongation were found at the precise site of the lateral geniculate bodies.CONCLUSIONAnterograde (pregeniculate) and retrograde (postgeniculate) transsynaptic degeneration of the second neurons of the visual pathway produce alterations in MR signal.     

Mechanism of the antihypertensive effect of FCE 22716, a new ergoline derivative, in the spontaneously hypertensive rat

Both acute and chronic oral administration (1-20 mg/kg) of FCE 22716, a new ergoline derivative, resulted in a dose-related fall of arterial blood pressure lasting for more than 6 h. Tachycardia was observed only at high dosages. Yohimbine, propranolol and indometacin did not modify its antihypertensive effect; on the other hand pretreatment with prazosin, a selective alpha 1-adrenoceptor antagonist and pithing, almost completely neutralized its antihypertensive effect. Haloperidol, a dopamine antagonist that crosses the blood-brain barrier, also antagonized FCE 22716 activity. The lack of effects of domperidone (DA2-receptor antagonist selectively acting on the periphery) together with the finding that norepinephrine and epinephrine levels were unchanged after treatment with FCE 22716, seem to rule out an involvement of peripheral DA2-receptors. Both in vitro (isolated organs) and in vivo the compound antagonized responses mediated by stimulation of alpha 1-adrenoceptors and S2-receptors. Radioligand binding studies in different cerebral regions are in line with the above reported in vitro and in vivo results. These data suggest that FCE 22716 is endowed with a multitarget mechanism of action, mainly involving blockade of alpha 1-adrenoceptors and S2-receptors.     

Efficacy and safety of ciprofloxacin in the treatment of UTIs and RTIs in patients affected by liver diseases

The clinical efficacy and the safety of ciprofloxacin was studied in 92 patients (aged 26 to 83 years; mean 57.5 years) affected by urinary tract infections (UTI) and respiratory tract infections (RTI) suffering also with various liver diseases. Ciprofloxacin was given orally at different dose regimens: 500 mg b.i.d. (22 cases), 250 mg b.i.d. (20 cases), 500 mg s.i.d. (20 cases) for the treatment of UTIs; 500 mg b.i.d. (ten cases) and 250 mg b.i.d. (20 cases) for the treatment of RTIs. The doses were not correlated to the severity of the infections. Patients were treated for five to 15 days. All the bacteria isolated from sputum or urine before treatment were sensitive to ciprofloxacin (MIC range 0.015 mg/1 to 8 mg/1). The clinical and bacteriological responses were favourable in a high percentage of patients both for RTIs and UTIs, irrespective of the dose. Side effects were infrequent (7%) and mild (nausea, gastralgia, oral candidosis), never requiring the interruption of the treatment. No change in the blood chemistry tests was observed at any dose.Die klinische Wirksamkeit und Sicherheit von Ciprofloxacin wurde bei 92 Patienten (Alter 26 bis 83 Jahre, im Mittel 57,5 Jahre), die an verschiedenen Leberkrankheiten litten, bei interkurrent aufgetretenen Harnwegs- und Atemwegsinfektionen geprüft. Ciprofloxacin wurde in verschiedenen Dosierungen oral verabreicht. Zur Behandlung von Harnwegsinfektionen wurden Dosierungen von 500 mg zweimal täglich (22 Fälle), 250 mg zweimal täglich (20 Fälle) oder 500 mg in einer täglichen Einzeldosis (20 Fälle) verabreicht. Atemwegsinfektionen wurden mit zweimal täglich 500 mg (10 Fälle) oder mit zweimal täglich 250 mg (20 Fälle) behandelt. Die Dosen wurden nicht nach dem Schweregrad der Erkrankung gewählt. Die Behandlungsdauer betrug fünf bis 15 Tage. Alle aus Sputum oder Urin vor der Therapie isolierten Bakterien waren für Ciprofloxacin empfindlich (MHK-Werte 0,015 mg/l bis 8 mg/l). Bei einem hohen Prozentsatz der Patienten mit Atemwegs- und Harnwegsinfektionen wurden unabhängig von der Dosierung günstige klinische und bakteriologische Ergebnisse erzielt. Nebenwirkungen traten selten auf (7%) und waren leicht (Übelkeit, Magenschmerzen, orale Candidiasis). Ein Therapieabbruch war in keinem Fall nötig. Bei keiner der angewandten Dosierungen waren Änderungen in den klinisch-chemischen Parametern festzustellen.     

FG syndrome in a premature male

A 30-week premature male infant is presented with dolichocephaly, frontal bossing, down-slanting palpebral fissures, hypertelorism, long philtrum, micrognathia, cleft palate, and imperforate anus. He is the fifth patient to be presented with FG syndrome and sensorineural deafness. The patient's syndromic manifestations became more obvious during an inpatient observation period of 3 months.     

Hormones and the immunological capacity. V. Modification of growth hormone-producing cells in the adenohypophysis of neonatally thymectomized germ-free mice: an electron microscopical study

An electron microscopical study has been carried out to evaluate the effect of neonatal thymectomy on the hypophysis of germ-free mice at different times after the operation. The results fully confirm the previous findings in neonatally thymectomized, conventional mice. Also neonatal thymectomy in germ-free mice results in degranulation of growth hormone-producing cells in the anterior pituitary gland. A large number of these cells show an enlarged endoplasmic reticulum with formation of cisternae and loss of hormone granuli. This alteration of growth hormone-producing cells is similar to that observed in other cells of the hypophysis after removal of other target glands such as thyroid or gonads. The changes in the growth hormone-producing cells in neonatally thymectomized germ-free mice occur even in the first days after birth, when the number of differentiated growth hormone-producing cells is still very low.

Some thymectomized germ-free mice showed symptoms of the wasting syndrome but the alterations in their hypophysis were not more pronounced than those observed in thymectomized germ-free but nonwasting mice. The data fit well our suggestion that the perinatal thymus is under hypophysial control and that immunological maturation depends on endocrine function.

     

Uncoupling of inflammatory chemokine receptors by IL-10: generation of functional decoys

As originally demonstrated for the interleukin 1 (IL-1) type II receptor, some primary proinflammatory cytokines from the IL-1 and tumor necrosis factor families are regulated by decoy receptors that are structurally incapable of signaling. Here we report that concomitant exposure to proinflammatory signals and IL-10 generates functional decoy receptors in the chemokine system. Inflammatory signals, which cause dendritic cell (DC) maturation and migration to lymphoid organs, induce a chemokine receptor switch, with down-regulation of inflammatory receptors (such as CCR1, CCR2, CCR5) and induction of CCR7. Concomitant exposure to lipopolysaccharide (LPS) and IL-10 blocks the chemokine receptor switch associated with DC maturation. LPS + IL-10-treated DCs showed low expression of CCR7 and high expression of CCR1, CCR2 and CCR5. These receptors were unable to elicit migration. We provide evidence that uncoupled receptors, expressed on LPS + IL-10-treated cells, sequester and scavenge inflammatory chemokines. Similar results were obtained for monocytes exposed to activating signals and IL-10. Thus, in an inflammatory environment, IL-10 generates functional decoy receptors on DC and monocytes, which act as molecular sinks and scavengers for inflammatory chemokines.     

Towards improved clinical characterization of Leber congenital amaurosis: neurological and systemic findings

Leber congenital amaurosis (LCA) is the most severe form of inherited retinal dystrophy that presents in infancy. LCA is both clinically and genetically heterogeneous. The aim of our study was to clarify the clinical aspects of LCA and to contribute to improved characterization of the disorder. We studied 40 children affected by LCA (mean age at first observation: 19 months, range: 8-50 months), who underwent a comprehensive evaluation that included: neurophthalmological evaluation, electroretinogram (ERG), and visual evoked potentials (VEPs), general and neurological examinations, developmental assessment using scales for visually impaired children, neuroradiological examinations, hepatic and renal function and metabolic investigations, brainstem auditory evoked potentials (BAEPs), EEG, and hand radiographs. Analyses of known LCA genes are ongoing. The subjects are still being followed up at 6-/12-month intervals. All the subjects fulfilled De Laey's criteria for LCA. The neurological examination was abnormal in 31 cases (hypotonia, ataxia with/without associated cerebellar signs). Cognitive development was normal in 24 cases, borderline in five, and subnormal in 11. Mild and nonspecific alterations on MRI were present in seven cases, and "molar tooth" sign in four; all the others had a normal neuroradiological picture. Among the subjects presenting with neurological signs, a subgroup (13 patients) emerged that was characterized by systemic (skin, kidney, liver) involvement. Our data confirm that LCA is a heterogeneous entity that can present as an isolated ocular manifestation, or in association with neurological and systemic abnormalities and support the need for a multidisciplinary approach to this entity and for genotype-phenotype studies.