De la historia antigua de los métodos iodométricos: de Robert Bunsen a Karoly Tham / Ancient history of the iodometric methods: from Robert Bunsen to Karoly Tham

La contribución más importante en el ámbito de la iodometría se debe a Bunsen, quien describe la determinación de una amplia variedad de sustancias oxidantes liberando el yodo a partir del ioduro potasio, y valorándolo con ácido sulfuroso. Bunsen tenía predilección por el trabajo cuantitativo y era un genio en el diseño de la ciencia aplicada aunque no patenta los dispositivos que idea. Da un impulso decisivo a la institucionalización de la farmacia alemana en el siglo XIX, interesándose por el desarrollo de la educación farmacéutica. Heinrich Schwarz tras estudiar en de Halle y pasar por Giessen marcha al laboratorio de Pelouze en París, donde se familiariza con los métodos volumétricos de análisis, trabajando a su regreso a Alemania en este campo. Propone reemplazar el ácido sulfuroso utilizado por Bunsen en las valoraciones con yodo por tiosulfato sódico, lo que supuso un gran avance. Theophile Pelouze, farmacéutico, es fundamental para entender las conexiones con Schwarz y también con Bunsen. El trabajo concluye con la determinación de azúcares propuesta por Arthur Barreswill modificada por Fehling, y con la determinación de la pureza del ioduro de potasio del comercio

The most important contribution in the field of iodometry is due to Bunsen, who describes the determination of a wide variety of oxidizing substances by releasing iodine from iodide potassium, and assessing it with sulphurous acid. Bunsen had a predilection for quantitative work and was a genius in the design of applied science, although he does not patent the devices that idea. It gives a decisive impulse to the institutionalization of the German pharmacy in the 19th century, taking an interest in the development of pharmaceutical education. Heinrich Schwarz after studying in Halle and going through Giessen goes to the Pelouze laboratory in Paris, where he becomes familiar with the volumetric methods of analysis, working on his return to Germany in this field. It proposes to replace the sulphurous acid used by Bunsen in the evaluations with iodine by sodium thiosulphate, which represented a great advance. Theophile Pelouze, pharmacist, is essential to understand the connections with Schwarz and also with Bunsen. The work concludes with the determination of sugars proposed by Arthur Barres will modified by Fehling, and with the determination of the purity of the potassium iodide of the trade

Calcifilaxis no urémica mediada por acenocumarol / Non-uremic calciphylaxis due to acenocoumarol

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Tiosulfato sódico para el tratamiento de la calcifilaxia inducida por acenocumarol en un paciente sin enfermedad renal crónica / Sodium thiosulfate for the treatment of acenocumarol-induced calciphylaxis in a patient with preserved kidney function

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Tratamiento con tiosulfato de sodio tópico en calcifilaxia de paciente con trasplante renal activo / Treatment with sodium thiosulfate in calciphylaxis of topical active renal transplant patient

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Calcifilaxia. Estudio de 9 casos / Calciphylaxis. A review of 9 cases

Fundamento y objetivo: La calcifilaxia es una vasculopatía cutánea isquémica de vasos de pequeño tamaño con una alta morbimortalidad. Hasta el momento actual han sido publicadas muy pocas series de pacientes con esta enfermedad, ninguna procedente de un hospital español. Los principales objetivos de este trabajo son analizar el perfil demográfico, clínico e histológico de los pacientes diagnosticados de calcifilaxia en nuestro servicio, para identificar posibles factores de riesgo y potenciales estrategias terapéuticas. Material y método: Estudio retrospectivo de los casos vistos en el Servicio de Dermatología con diagnóstico de calcifilaxia con una biopsia confirmatoria, en el periodo de enero de 2010 a agosto de 2015. Resultados: Se estudiaron 9 pacientes, con edades de 76-86 años. Todos tenían comorbilidades cardiovasculares y el 67% tenía insuficiencia renal. Se observó un 33% de mortalidad. Conclusiones: Ante el posible diagnóstico de calcifilaxia debe realizarse una analítica sanguínea completa para descartar otras causas de úlceras cutáneas. El tratamiento de estos pacientes debe llevarse a cabo por un equipo multidisciplinar. Resaltamos el papel del tiosulfato sódico en el tratamiento de esta entidad (AU)

Background and objective: Calciphylaxis is a cutaneous ischaemic vascular disease of small vessels with high morbidity and mortality. To date very few series of patients with this disease have been published, none from a Spanish hospital. The main objectives of this work are to analyze the demographic, clinical and histological profile of patients diagnosed in our department to identify risk factors and potential therapeutic strategies. Material and method: We made a retrospective study of the cases seen in the dermatology department with a diagnosis of calciphylaxis and who had a confirmatory biopsy in the period between January 2010 to August 2015. Results: Nine patients were studied, with an age range of 76-86 years. All had cardiovascular comorbidities and 67% had renal failure. A 33% mortality was observed. Conclusions: Faced with a possible diagnosis of calciphylaxis, a complete blood analysis is mandatory to rule out other causes of skin ulcers. The management of these patients should be undertaken by a multidisciplinary team. We emphasize the role of sodium thiosulfate in the treatment of this condition (AU)

Relationship between clinical factors and the incidence of toxicity after intra-arterial chemoradiation for head and neck cancer.

BACKGROUND AND PURPOSE: Concomitant chemoradiation is more and more used for advanced head and neck cancer. It improves local control and survival compared to radiotherapy alone, but goes along with serious toxicity. This study was set up to determine the relationship between patient-, tumour- and treatment-related factors and acute/late toxicity after concomitant chemoradiation. PATIENTS AND METHODS: One hundred and twenty-five consecutive patients with newly diagnosed inoperable stage III and IV head and neck cancer were enrolled for intra-arterial chemoradiation. There were 28 women (22%) and 97 men (78%) and the mean age was 55 years (range 30-80). One hundred and nine patients had stage IV disease (87%), 16 patients (13%) had stage III disease. Statistical analyses were performed to identify an association between factors and acute/late toxicity. RESULTS: There were eight treatment-related deaths (6%). Severe acute toxicity (grade 3-4), mainly mucositis and dysphagia as categorized by the RTOG toxicity criteria, was recorded in 51% of the patients. Leucopenia (grade 3-4) occurred in 39% and aspiration pneumonia in 20% of patients. Tracheotomy was necessary in 15 (12%) patients. Neurological complications during treatment occurred in 3 (2%) patients. Severe late toxicity occurred in 34% of the patients. The most important of these were pneumonia (14%), osteoradionecrosis (9%) and swallowing problems with permanent percutaneous gastrostomy (20%). Statistical analysis did show a significant association between site and severe acute mucositis (p = 0.007), site and osteoradionecrosis (p = 0.014) and age and xerostomia (p = 0.004). CONCLUSIONS: Chemoradiation is frequently associated with serious toxicity. Oral cavity tumours and older age are related to acute mucositis/osteoradionecrosis and xerostomia, respectively.

[Sodium gold thiosulfate therapy: an open, viewed, multicenter trial in rheumatoid arthritis patients followed for two years]. / Terapia con tiosolfato di sodio e oro: studio osservazionale, aperto, multicentrico in pazienti con artrite reumatoide seguiti per due anni.

OBJECTIVE: To evaluate if parenteral gold-therapy with Sodium gold thiosulfate is effective and safe for the treatment of rheumatoid arthritis we began an open, multicenter trial. METHODS: 126 rheumatoid arthritis patients were treated with Sodium gold thiosulfate for two years. Efficacy, quality of life, progression of joint damage, inflammatory parameters and side effects were evaluated. RESULTS: Gold salts reduced joint inflammation and improved subjective and objective symptoms, quality of life and activity of illness within 6 months. Side effects appeared in 13,8% of all cases and regressed, promptly, when gold therapy stopped. The poor efficacy caused the interruption and the change from the gold therapy to others disease-modifying anti-rheumatic drugs (DMRDs) in 17,8 % of the patients. CONCLUSIONS: The follow-up showed Sodium gold thiosulfate was effective in Rheumatoid Arthritis and the survival in therapy was of 77,8% to one year and of 68,4% to two years.

The assessment of quality of life as a measure of gold salts treatment efficacy in rheumatoid arthritis.

BACKGROUND: In the evaluation of functional status of patients with rheumatoid arthritis (RA) the health related quality of life is currently considered important because of its approach to various components of life, such as social, psychological, and physical aspects. We used the Stanford Health Assessment Questionnaire (HAQ) to assess the improvement of functional status in patients with RA treated with gold salts. METHODS: In a prospective investigation 91 patients with RA in anatomical stage I, II, or III, 66 females and 25 males, with a mean age of 53.17 years, were evaluated during medical treatment in a 1-year follow-up. The treatment consisted in sodium aureothiosulphate, plus corticosteroids and NSAID. The assessments were done during ambulatory visits, at baseline and after 6 and 12 months of treatment, by HAQ as well as by other parameters such as Ritchie Index, visual analog scale (VAS), and morning stiffness. A group of 19 RA patients included by the same criteria and treated only by corticosteroids and NSAID was used as control for the first 6 months of the study. RESULTS: HAQ scores and other parameters were significantly lower (p=0.0001) at the 6th and 12th month measurements when compared with baseline. In the control group only a significant difference in the VAS score was detected. CONCLUSIONS: All the parameters measured in our study were useful in detecting clinical improvement in RA patients treated with sodium aureothiosulphate plus corticosteroids and NSAIDs, but the HAQ provides a more global assessment of the patient's status.

Long-term outcome with gold thiosulphate and tiopronin in 200 rheumatoid patients.

Two hundred rheumatoid patients were prospectively studied over a five-year period. One hundred and three received tiopronin (T) and 97 were treated with gold thiosulphate (GTS). At the end of the five-year period, similar percentages of patients dropped out because of lack of efficacy or because of major toxicities. Likewise, the percentages of patients still receiving the original drug in the two drug regimens at the 5th year of follow-up were 27.8% (GTS) vs. 25.2% (T), respectively.

[The effect of a gold complex on experimental arthritis induced by immunization with type II collagen]. / Pokus o ovlivnení experimentální artritidy, vyvolané imunizací kolagenem typu II, komplexem zlata.

Gold complexes are used in the treatment of rheumatoid arthritis for some 60 years by now. The authors used therefore a gold complex, sodium aurothiosulphate (ATSS) to influence the experimental model of arthritis induced by immunization with type II collagen in laboratory rats. To the first group of laboratory rats ATSS was administered concurrently with the first immunization dose, to the second group with the second immunization dose and to the third group in the course of arthritis. ATSS was administered to individual groups every week by the i. m. route, 20 mg/kg body weight. In all three groups a reduction of arthritic symptoms was observed, however, in group three to a much lesser extent than in groups one and two. The results of the experiment indicate clearly that ATSS was able to suppress the development of collagen induced arthritis, if administered not later than with the second immunization dose. As the formation of antibodies against type II collagen was not suppressed, it may be assumed that the activation of the complement system was blocked by the bond of the gold complex with the C1q component. It has been proved already previously that the interaction of C1q with gold complexes is very rapid.

Antiarthritic synergism of combined oral and parenteral chrysotherapy. II. Increased inhibition of activated leukocyte oxygen burst by combined gold action.

We have observed an antiarthritic effect of combined chrysotherapy in adjuvant arthritis. Since superoxide radicals (O2-) are potent mediators of rheumatoid inflammation, we studied the combined effect of auranofin (AF) and injectable golds on luminol-dependent chemiluminescence (LDCL) and O2- generation by cytochrome-c reduction of activated leukocytes by different receptor-mediated stimuli: phorbol myristic acetate, 10(-6) M; f-Met-Leu-Phe, 10(-6) M; and poly-L-histidine, 10(-5) M. AF, 0.6 and 0.9 micrograms Au/ml, inhibited 34 and 58% of O2- generation, respectively; the addition to AF of 0.3 micrograms Au/ml of gold thiosulfate (GTS) increased this inhibition to 84 and 97% of the oxygen burst. Similar synergistic potentiation inhibition was obtained by LDCL. When the inhibition of O2- generation by the combined action of AF and GTS was compared with AF + gold sodium thiomalate (GTM), only GTS showed an activation on AF's inhibition of the oxygen burst of human leukocytes. The ligand thiosulfate in equimolar concentrations to GTS had a statistically significant (P less than 0.01) inhibitory effect on AF's blockade of O2- generation during the first 5 min of the interaction with the PMNs; thiomalate had no effect. Sequential pretreatment of PMNs with AF and GTS on O2- generation revealed that for synergism of combined gold action to take place, the cell membrane had to be subjected first to the action of oral gold or to the simultaneous combined action of oral and parenteral gold.(ABSTRACT TRUNCATED AT 250 WORDS)

Antiarthritic synergism of combined oral and parenteral chrysotherapy. I. Studies in adjuvant-induced arthritis in rats.

In comparative clinical studies of auranofin (AF, oral gold) and parenteral gold in the treatment of rheumatoid arthritis, no difference in efficacy was detected. Since the pharmacologic profiles of these compounds are different, we studied their combined effect on adjuvant arthritis (AA). The effect of AF alone and combined with gold sodium thiomalate (GTM) or gold sodium thiosulfate (GTS) on the excretion of urinary hydroxyproline (UHP) and urinary calcium (UCa), and the articular index of arthritic rats was followed during five weeks of treatment. The excretion of UHP and UCa was significantly inhibited (P less than 0.005) in rats treated with AF combined with GTM or GTS as compared with animals treated with the individual gold compounds. However, the articular index only decreased significantly (P less than 0.02) in the group of rats treated with AF + GTS. The present studies open the possibility that combined treatment with oral and injectable gold provide a new approach for chrysotherapy with an increased antiarthritic potency.

[The testing of long-term antirheumatics in animals]. / Zur Testung von Basisantirheumatica am Tier.

There is no group proof of long acting antirheumatics (LAA) in laboratory animal models, and it is not to be expected without an identical rheumatoid arthritis model in animals and with regard to the heterogeneity of LAA. However, LAA are to be detected according to D-penicillamine-like, levamisol-like etc. actions, which can be disclosed in the adjuvant arthritis as well as in the B. pertussis-vaccine pleuritis in rats the latter model best by including parameters of inflammatory exudate cells. Modification of the models or of model parameters (BCG-sensibilization, PPD reaction, vasoreactivity, RNA content of exudate cells, SH groups, copper zinc) are hardly advantageous, contrarily to dosage. Other models, among them paw edemas, do not permit sufficient testing of LAA, even not the methyl-albumin mice paw edema. There is no problem of pharmacologically separating LAA actions from nonsteroidal or steroidal antiphlogistics actions.

Toxicity due to remission inducing drugs in rheumatoid arthritis. Association with HLA-B35 and Cw4 antigens.

Twenty-five patients with rheumatoid arthritis (RA) who developed toxicity while taking remission inducing drugs and 30 without toxicity were studied for possible associations with class I and II HLA antigens. A strong association has been found between nephritis and dermatitis due to Tiopronin (a D-Penicillamine like compound) and class I antigens B35-Cw4, and between dermatitis due to gold thiosulphate and B35. Compared to healthy controls a lower DR5 frequency was observed in patients with RA except for the Tiopronin related nephritis group.

Sulphasalazine: a safe, effective agent for prolonged control of rheumatoid arthritis. A comparison with sodium aurothiomalate.

The place of sulphasalazine in the management of rheumatoid arthritis over prolonged periods of time has been compared and contrasted with that of sodium aurothiomalate. One hundred and forty-three patients (59 on sulphasalazine, 84 on sodium aurothiomalate) have been treated for periods of up to 42 months. Sulphasalazine is highly effective for some patients, though probably less frequently than sodium aurothiomalate. However, its safety profile is far superior, and very long-term treatment with sulphasalazine is a safe option for treatment of rheumatoid arthritis.