Neomycin inhibits angiogenin-induced angiogenesis

A class of angiogenesis inhibitor has emerged from our mechanistic study of the action of angiogenin, a potent angiogenic factor. Neomycin, an aminoglycoside antibiotic, inhibits nuclear translocation of human angiogenin in human endothelial cells, an essential step for angiogenin-induced angiogenesis. The phospholipase C-inhibiting activity of neomycin appears to be involved, because U-73122, another phospholipase C inhibitor, has a similar effect. In contrast, genistein, oxophenylarsine, and staurosporine, inhibitors of tyrosine kinase, phosphotyrosine phosphatase, and protein kinase C, respectively, do not inhibit nuclear translocation of angiogenin. Neomycin inhibits angiogenin-induced proliferation of human endothelial cells in a dose-dependent manner. At 50 microM, neomycin abolishes angiogenin-induced proliferation but does not affect the basal level of proliferation and cell viability. Other aminoglycoside antibiotics, including gentamicin, streptomycin, kanamycin, amikacin, and paromomycin, have no effect on angiogenin-induced cell proliferation. Most importantly, neomycin completely inhibits angiogenin-induced angiogenesis in the chicken chorioallantoic membrane at a dose as low as 20 ng per egg. These results suggest that neomycin and its analogs are a class of agents that may be developed for anti-angiogenin therapy.     

Neomycin: microbiological assay or liquid chromatography?

In a multicentre study involving six laboratories, a microbiological assay was performed on three neomycin samples containing respectively, 0.12, 2.1 and 11% (m/m) of neomycin C, as well on a pure neomycin C sample. The potency was determined according to the European Pharmacopoeia method but using a neomycin B base standard. The relative standard deviations between laboratories (RSD) on the potencies varied from 4.8 to 50%, depending on the sample examined. The RSD increased with the neomycin C content of the samples and the highest RSD values were observed for the pure neomycin C sample. The activity of neomycin C relative to neomycin B was found to be 62% by diffusion (RSD:41%) and 56% by turbidimetry (RSD: 50%). This confirmed that the presence of neomycin C in a neomycin sample influences the reproducibility of the microbiological assay. T estimate the influence of this effect on official standard, their composition was verified by liquid chromatography. The neomycin C base content of the standards varied between 0.4 and 5.8% (m/m). Based on the results obtained and on formerly published reports discussing problems encountered with microbiological assay of neomycin, it is proposed to introduce liquid chromatography in official monographs to replace microbiological assay.     

Sadism revisited

Sadism has been for a long time, among psychoanalytic and other writers, the subject of extensive theorizing and controversy. This paper takes a fresh look at the many dimensions (sexual, characterological, neurotic, psychotic, neurological) of this old aberrations.     

Benzodiazepines revisited

Glucagonoma is an endocrine tumor of almost exclusively pancreatic origin which is rarely associated with a clinical syndrome mainly characterized by migratory necrolytic erythema, hyperglycemia, weight loss, hypoaminoacidemia and anemia. Ten to 30% of the patients may present thromboembolic phenomenon, deep vein thrombosis and pulmonary embolism which often lead to the death of the patient. We report the case of a patient diagnosed with pancreatic glucagonoma the presentation of which consisted in episodes of repeated deep vein thrombosis without associated migratory necrolytic erythema.     

Cyclazocine revisited

Recently synthesized compounds which have long-term mu antagonist activity and short-term kappa agonist effects prevent self-administration of cocaine and morphine in rats. Cyclazocine, a compound synthesized in 1962 and studied in animals and man in the 1960's and in the early 1970's is a mu antagonist in rats and man and is a potent kappa agonist in both species. It also prevents self-administration of cocaine and morphine in rats. Although it produces unpleasant side effects in man, subjects become tolerant to these side effects but not to the antagonistic actions of the drug after prolonged administration.     

Recovery revisited

Recovery of mechanical properties during annealing of deformed metals has been modelled based on a microstructural representation comprising two elements, (i) the cell/subgrain structure (size δ) and (ii) the dislocation density (ρ) within the subgrains. These two microstructural elements are treated as independent internal state variables and the recovery of flow stress obtained by adding the time dependent contributions due to subgrain growth [σ ∝ 1/δ(t)] and dislocation network growth

. The growth of a dislocation network has been treated in terms of thermally activated glide, thermally activated cross-slip, climb and solute drag as rate-controlling mechanisms. Subgrain growth has been analysed in a manner analogous to normal grain growth, with climb of the boundary dislocations being the rate controlling mechanism. The model has successfully been applied in the interpretations of recovery observations in iron, aluminium and AlMg alloys. It follows from the theoretical treatment as well as from the analysis of experimental data that the characteristic logarithmic time dependence of low temperature recovery is the result of a reaction controlled either by thermally activated glide of jogged screw dislocations or by solute drag. It has been demonstrated that a mechanism based on thermally activated cross-slip does not apply in this context.     

Theophylline revisited

For over 50 years, theophylline has been used regularly for the management of chronic asthma. However, because of its perceived narrow therapeutic index and the fact that it has been considered a weak bronchodilator, the use of theophylline therapy has diminished. Furthermore, with the introduction of newer pharmacologic agents and recommendations in widely accepted guidelines, both nationally and internationally, have further contributed to its decreased use. For years, theophylline has not only been considered a bronchodilator, but for many clinicians, an agent that could be used to enhance respiratory muscle function and mucociliary clearance and act at the level of the central nervous system to enhance ventilation. These properties were felt to be potentially useful for patients with severe exacerbated asthma. Recent studies have suggested that theophylline therapy can play a beneficial role in the management of both chronic stable asthma and exacerbated disease treated in the emergency department setting. Furthermore, a growing body of evidence suggests that theophylline has certain antiinflammatory and immunomodulating properties, even at plasma concentration levels below the accepted therapeutic range. If this is true, then theophylline may act best as a controller medication in the management of asthma. Because of its low cost and its ease of administration, theophylline therapy should be revisited and discussed as not only a reliever of bronchospasm, but a controller of chronic asthma.     

Asylums revisited

The authors revisited Erving Goffman's Asylum (Saint Elizabeths Hospital) and found both the "institutionalization" and "secondary adjustment" phenomena he described 20 years ago. However, they question whether secondary adjustments necessarily follows institutionalization. They also express doubt that institutionalization should be condemned automatically and suggest that it may in fact be the approach of choice for some patients.     

Vesicorectostomy revisited

Between 1948 and 1959 vesicorectostomy, a permanent anastomosis between the bladder and rectum, was constructed in 7 male patients. Scattered reports of this procedure exist but none since 1959 and long-term followup has never been reported. we present long-term followup, including renal function, excretory urography and voiding cystorectography, and review the quality of life in the 7 patients. The most frequent complication was stenosis of the anastomosis. None of the patients in this series with normal preoperative upper tracts showed radiographic or chemical deterioration postoperatively. Since this procedure maintains urinary continence, does not disturb the normal physiology of the ureterovesical junction and minimizes urinary reabsorption its use should be considered in certain patients as an alternative method of urinary diversion.     

Bilateral vestibulopathy revisited

Bilateral vestibular failure (BVF) is an often undetected disorder of the peripheral labyrinths or the eighth nerves. Key symptoms are oscillopsia during locomotion or head movements and unsteadiness, particularly in the dark. Diagnosis is made by a bedside test for defective vestibulo-ocular reflex and the absence of nystagmic reaction to both caloric and rotatory pendular testing. Most frequent etiologies include ototoxicity, cerebellar degeneration, meningitis, neuropathies, sequential vestibular neuritis, autoimmune disorders, tumors, and miscellaneous otological diseases. Idiopathic BVF is found in more than twenty percent of the patients. Recovery is possible but mostly incomplete. Somatosensory and visual input largely substitute the vestibular deficit for spatial orientation, postural balance and ocular motor control.     

Netherton syndrome revisited

Because coeliac disease often presents atypically it is underdiagnosed. It is suggested that the detection rate may be increased by 12% if serology is used to identify cases of occult enteropathy. All adults noted incidentally to be R1 anti-reticulin antibody (ARA) positive in the course of routine autoantibody testing of 6532 sera over one year were followed. None of the eight patients with seropositive serum was suspected of having coeliac disease. All eight had high titres of IgA anti-gliadin and IgA anti-endomysial antibodies, neither of which is detected in a routine autoantibody test, in addition to IgA R1-ARA. On clinical review coeliac disease was considered probable in only one patient, but because of the strong serological evidence of gluten sensitivity, jejunal biopsy was advised in all eight. Seven agreed and all had villous atrophy and crypt hyperplasia in keeping with coeliac disease. Six of the seven presented initially with vague symptoms such as tiredness or arthralgia. These symptoms disappeared after several weeks of gluten withdrawal. Forty two sera showing reticulin staining patterns other than R1 were used as controls. Low titre IgA anti-gliadin was noted in two of 42 but none had IgA anti-endomysial antibody. These 42 cases were not recommended for biopsy. During our study 58 other new adult cases of coeliac disease were diagnosed, primarily on clinical rather than serological grounds, at the four hospitals that request autoantibody studies. Occult coeliac disease detected serologically thus increased the overall incidence of coeliac disease by 12% from 58 to 65 cases. R1-ARA, even in the absence of the expected symptoms and signs of coeliac disease, is an indication for jejunal biopsy and is a reliable indicator of occult coeliac disease.