Treatment of syphilis by arylarsonates

(1) The chief points about ATOXYL are its varying composition, its liability to contamination during the process of manufacture, its relative toxicity and its liability to decomposition under various physical and chemical conditions. Besides, there is its injurious action on the neuro-retinal visual apparatus. There is a conflict of opinion regarding its value. Although it is able to modify primary, secondary and various tertiary specific lesions, it fails in hereditary and parasyphilitic conditions. The fact that it sometimes succeeds where Mercury and the Iodides have failed, is no reason why it should be adopted as a routine mode of treatment in human Syphilis in view of the better results obtained by some of the newer arsenical preparations. The only conditions where it is likely to replace Mercury are in the various cases - already mentioned -- where that drug is contra-indicated or cannot be tolerated.(2) SOAMIN recommends itself to us on account of its definite chemical composition, its purity and relative non -toxicity. There is a unanimity of opinion as to its beneficial effects in primary, secondary and tertiary specific lesions. Authorities are also agreed as to its failure in hereditary and parasyphilitic conditions. It certainly succeeds where Mercury and the Iodides sometimes fail or are contra-indicated. Very seldom does it give rise to toxic effects or to visual disturbances. In conditions where Mercury is contra-indicated or useless, it is likely to replace it, and again in the Tropics where on account of the debility caused by climatic and malarial conditions it cannot be given. It certainly causes an increase in weight in almost every case and acts as a tonic in tropical debility. Its advantage over Mercury is that it causes no salivation, stomatitis or spongy gums. Likewise, in moderate remedial doses, it does not cause diarrhoea, a point of great value, as compared with Mercury, in the tropics where diarrhoea is such a prevalent disease or symptom.(3) ARSACETIN recommends itself to us on account of its purity, marked stability and the rapid manner in which it modifies all forms of the disease except hereditary and parasyphilitic ones. Compared with Soamin and Atoxyl, the weight of clinical evidence is 108. in its favour. It does not cause neuro-retinal ocular disturbances (like Atoxyl), is relatively nontoxic, well borne and certainly indicated where Mercury is useless or contra-indicated. When possible, it should be followed by a mercurial course, and is indicated in tropical conditions. Under its action, patients rapidly increase in weight and it acts indirectly as a tonic.Colonel Lambkin, in speaking of this drug and. Soamin, said that the good results he obtained in his cases strengthened his conviction that we had in them, a secondary specific for Syphilis, at least from a preventive and remedial point of view. As regards the former, he had then under his care cases with undoubted primary specific lesions which were treated with Soamin and which were closely observed every week for ten months without developing any further sign of the disease. From the remedial point of view the good results he obtained speak for it. But as a curative agent, it is beyond us all at present to give a positive answer to this all -important question; time and clinical experience alone would enable us to do so. This could not be done until it was proved beyond doubt that arylarsonates were capable of permanently expelling the spirochaetae pallida from the system, as indicated by the patient being rendored capable of re- infection. Neisser's successful experiments on apes from this point of view justified us in hoping for this end. Until the question as to the capability of arylarsonates bringing about a permanent cure was fully established, he would give Mercury after a course of treatment by arylarsonates. Later on, the same author(2)in speaking of the arylarsonates, said that our present knowledge of the power of these arsenical salts over Syphilis was in a very elementary stage, but he looked forward to further experience of them and improved technique leading us to that goal in the treatment of Syphilis which had already been attained with dourine. Regarding Arsacetin, Neisser(3)says that he has hitherto applied the mercurial and arsacetin treatment simultaneously, but perhaps they could be carried out alternately.(4) ARSENO-PHENYL-GLYCIN has been fully dealt with elsewhere and it only remains for me to say that, despite the brilliant results which follow its administration, there is no likelihood, on account of its instability and the inconvenient form in which it is supplied, of it ever replacing Mercury, and even other arylarsonates like Soamin, Arsacetin, Atoxylate of Mercury and Salvarsan in the treatment of human Syphilis.In reviewing the arylarsonates hitherto discussed and used before the introduction of Salvarsan and Mercury Atoxylate, Colonel Lambkin said that it was far too soon to express an opinion as to whether they were likely to prove of permanent benefit in Syphilis or whether they were likely to replace Mercury in the disease, but the results were encouraging. Whether they had any abortive or prophylactic effect on the future development of the disease after inoculation, he was unable to speak except to note that when given at an early date they delayed and modified considerably the secondary signs of the disease and that they had very beneficial effects on all specific mucous ulcerations. It was well established, he thought, that in the arylarsonates we had a second specific for Syphilis, the importance of which could not well be exaggerated.(5) In MERCURY ATOXYLATE we have a very potent drug exerting both the specific actions of Atoxyl and Mercury on the spirochaetae, both in vitro and in corpore. It is far more potent than Calomel injections alone. If applied to suitable cases and care taken in its administration, it is a safe drug. Lambkin and others who have used it, prefer it to Mercury over which it has a decided advantage in the rapidity with which it controls the symptoms of the disease. I am of opinion that this drug will certainly displace the mercurial treatment of Syphilis.(6) SALVARSAN or Ehrlich Hata's "606" is the most potent drug hitherto discovered and applied to the treatment of human Syphilis in its protean aspects. Its stability, non -toxicity, ease of administration, rapidity of action, the fact that it does not affect the neuro-retinal visual apparatus, all speak in its favour. It is indicated in all forms of the disease viz. primary, secondary, tertiary and hereditary lues, while it has a marked effect in combating some of the symptoms occurrinm_ in parasyphilis. It has yielded marvellous results in alleviating the various crises of locomotor ataxia of specific origin. With the doses at present used, cases have been said to recur, but Professor Herxheimer, Dr H. Isaac and others have never seen them. Dr Leonor Michaelis found that the recovery was absolute in a few days in most of his cases, while Dr Gourwitsch and S. Bormann selected cases which had been treated with the most powerful of mercurial methods and found that the comparison of these with Arseno-benzol proved the over-whelming value of the latter.By way.of conclusion, I may say that from a personal experience of the effects produced by Salvarsan and the reports of eminent authorities, that the drug is absolutely superior in Syphilis to any other known drug, and. that a single injection, in a suitable case, will produce results obtained only after years of_ treatment with Mercury. This latter drug, however, is not to be discarded because it seems to have been proved that there are strains of spiroçhaetaç that are arsenic-proof. In the same way, there are strains that are Mercury-proof. Perhaps by using one drug after the other we may be able to destroy all these various strains and so bring about a permanent cure of the disease.In spite of the pre-eminence of Salvarsan as the best curative and prophylactic agent hitherto discovered for Syphilis, I venture to state that the last word has not yet been spoken on the treatment of. Syphilis

Quorum sensing architecture network in Escherichia coli virulence and pathogenesis

Escherichia coli is a Gram-negative commensal bacterium of the normal microbiota of humans and animals. However, several E. coli strains are opportunistic pathogens responsible for severe bacterial infections, including gastrointestinal and urinary tract infections. Due to the emergence of multidrug-resistant serotypes that can cause a wide spectrum of diseases, E. coli is considered one of the most troublesome human pathogens worldwide. Therefore, a more thorough understanding of its virulence control mechanisms is essential for the development of new anti-pathogenic strategies. Numerous bacteria rely on a cell density-dependent communication system known as quorum sensing (QS) to regulate several bacterial functions, including the expression of virulence factors. The QS systems described for E. coli include the orphan SdiA regulator, an autoinducer-2 (AI-2), an autoinducer-3 (AI-3) system, and indole, which allow E. coli to establish different communication processes to sense and respond to the surrounding environment. This review aims to summarise the current knowledge of the global QS network in E. coli and its influence on virulence and pathogenesis. This understanding will help to improve anti-virulence strategies with the E. coli QS network in focus. This review highlights the latest findings in the field of cell-to-cell communication systems in Escherichia coli and discusses the relevance of this complicated signalling network for the virulence and pathogenesis of this bacterium

Propagation of social representations

Based on a minimal formalism of social representations as a set of associated cognems, a simple model of propagation of representations is presented. Assuming that subjects share the constitutive cognems, the model proposes that mere focused attention on the set of cognems in the field of common conscience may replicate the pattern of representation from context into subjects, or, from subject to subject, through actualization by language, where cognems are represented by verbal signs. Limits of the model are discussed, and evolutionist perspectives are presented with the support of field data

Circum-Arctic mantle structure and long-wavelength topography since the Jurassic

The circum-Arctic is one of the most tectonically complex regions of the world, shaped by a history of ocean basin opening and closure since the Early Jurassic. The region is characterized by contemporaneous large-scale Cenozoic exhumation extending from Alaska to the Atlantic, but its driving force is unknown. We show that the mantle flow associated with subducted slabs of the South Anuyi, Mongol-Okhotsk, and Panthalassa oceans have imparted long-wavelength deflection on overriding plates. We identify the Jurassic-Cretaceous South Anuyi slab under present-day Greenland in seismic tomography and numerical mantle flow models. Under North America, we propose the “Farallon” slab results from Andean-style ocean-continent convergence around ~30°N and from a combination of ocean-continent and intraoceanic subduction north of 50°N. We compute circum-Arctic dynamic topography through time from subduction-driven convection models and find that slabs have imparted on average <1–16 m/Myr of dynamic subsidence across the region from at least 170 Ma to ~50 Ma. With the exception of Siberia, the main phase of circum-Arctic dynamic subsidence has been followed either by slowed subsidence or by uplift of <1–6 m/Myr on average to present day. Comparing these results to geological inferences suggest that subduction-driven dynamic topography can account for rapid Middle to Late Jurassic subsidence in the Slave Craton and North Slope (respectively, <15 and 21 m/Myr, between 170 and 130 Ma) and for dynamic subsidence (<7 m/Myr, ~170–50 Ma) followed by dynamic uplift (<6 m/Myr since 50 Ma) of the Barents Sea region. Combining detailed kinematic reconstructions with geodynamic modeling and key geological observations constitutes a powerful tool to investigate the origin of vertical motion in remote regions

Correspondence: Reply to ‘Numerical modelling of the PERM anomaly and the Emeishan large igneous province’

Tectonic plates and plate boundaries migrate substantially through time and mantle plumes are generally accepted to be mobile within the convecting mantle, but it has been proposed that large low shear velocity provinces (LLSVPs) could have been fixed and rigid for as much as 540 million years (Myr). The hypotheses of fixed and rigid LLSVPs cannot be easily tested in the absence of constraints on the past location of lowermost mantle structures. We evaluated the hypothesis9of lower mantle thermochemical structure fixity with numerical experiments. As in earlier studies, we argue that the location of lower mantle thermochemical structures has changed through time

Origin and evolution of the deep thermochemical structure beneath Eurasia

A unique structure in the Earth’s lowermost mantle, the Perm Anomaly, was recently identified beneath Eurasia. It seismologically resembles the large low-shear velocity provinces (LLSVPs) under Africa and the Pacific, but is much smaller. This challenges the current understanding of the evolution of the plate–mantle system in which plumes rise from the edges of the two LLSVPs, spatially fixed in time. New models of mantle flow over the last 230 million years reproduce the present-day structure of the lower mantle, and show a Perm-like anomaly. The anomaly formed in isolation within a closed subduction network ∼22,000 km in circumference prior to 150 million years ago before migrating ∼1,500 km westward at an average rate of 1 cm year^(−1), indicating a greater mobility of deep mantle structures than previously recognized. We hypothesize that the mobile Perm Anomaly could be linked to the Emeishan volcanics, in contrast to the previously proposed Siberian Traps

Parallel flow in Hele-Shaw cells with ferrofluids

Parallel flow in a Hele-Shaw cell occurs when two immiscible liquids flow with relative velocity parallel to the interface between them. The interface is unstable due to a Kelvin-Helmholtz type of instability in which fluid flow couples with inertial effects to cause an initial small perturbation to grow. Large amplitude disturbances form stable solitons. We consider the effects of applied magnetic fields when one of the two fluids is a ferrofluid. The dispersion relation governing mode growth is modified so that the magnetic field can destabilize the interface even in the absence of inertial effects. However, the magnetic field does not affect the speed of wave propagation for a given wavenumber. We note that the magnetic field creates an effective interaction between the solitons.Comment: 12 pages, Revtex, 2 figures, revised version (minor changes

Multiple cadherin extracellular repeats mediate homophilic binding and adhesion

The extracellular homophilic-binding domain of the cadherins consists of 5 cadherin repeats (EC1–EC5). Studies on cadherin specificity have implicated the NH2-terminal EC1 domain in the homophilic binding interaction, but the roles of the other extracellular cadherin (EC) domains have not been evaluated. We have undertaken a systematic analysis of the binding properties of the entire cadherin extracellular domain and the contributions of the other EC domains to homophilic binding