[REHABILITATION OF PATIENTS WITH URIC ACID AND MIXED UROLITHIASIS].

This paper presents evaluation of rehabilitation effectiveness of 113 patients aged 19-78 years diagnosed as having mixed and uric acid stones. 88 patients with uric acid stones 0,5-2,5 cm were assigned to group 1 and treated with Trometamol N parenteral litholis and a complex metaprophilaxis by dietary supplements Prolit and Urisan. 25 patients with mixed stones 1-3,5 cm were allocated to group 2 and treated with external shock wave lithotripsy and complex metaprophilaxis by dietary supplements Prolit Super Septo and Urisan. Positive results were achieved in all the patients. In the patients of group 1 the stones were completely dissolved. In group 2 treatment resulted in stone disintegration and clearance of small fragments 0,4 cm after partial dissolution.

Prebiotic properties of galursan HF 7K on mouse gut microbiota.

BACKGROUND: With the rise of antibiotic resistance, new alternatives are being sought to effectively modulate the characteristics of gut microbiota to obtain pathogen resistance without the use of antibiotics. In the past, an oligosaccharide derivative of carrots, galursan HF 7K (GHF7K), has been used clinically in Austria and recently in the fowl-industry to promote health. This study examined the potential role of GHF7K as a prebiotic to alter the gut microbiota in mice. METHODS: Mice were fed either a control diet (CT) or a diet containing 2% GHF7K in the water and chow for 2 weeks, and weight, food and water consumption, gut microbiota and ion composition of the intestinal fluid were examined. RESULTS: Dietary supplement of GHF7K did not alter mouse weight or daily food consumption. Additionally, no changes were observed in the total number of luminal or mucosa-associated bacteria populations in GHF7K-fed mice. GHF7K supplementation significantly altered the composition of luminal, and to a less extent, mucosa-associated bacterial populations at the level of the phyla, with region-specific differences. Similar to antibiotic use, Proteobacteria number was increased in the ileum and colon of GHF7K-fed mice, with no changes in the number of beneficial Lactobacillus and Bifidobacterium genera of phylum Firmicutes. Corresponding with the altered gut microbiota, changes in the ion composition of the intestinal fluid were observed. An increased Cl(-) concentration was observed in the duodenum and jejunum, while the Na(+) concentration was increased in the cecum of GHF7K-fed mice. Decreases were observed in the K(+) concentration in the cecum and distal colon. CONCLUSIONS: Dietary supplement of GHF7K is capable of altering the gut microbiota, which correlates to changes in the intestinal environment. These data suggest that GHF7K dietary supplement can purposefully be used to alter the gut microbiota, and thus could potentially represent an alternative approach to prophylactic antibiotic use.

[Treatment and metaphylaxis of urate and mixed urolithiasis].

We estimated the efficacy of combined treatment and metaphylaxis of urate and mixed urolithiasis in 87 patients aged 18-87 years. The patients were divided into two groups: 68 patients of group 1 (the size of the concrements between 5-25 mm) have undergone parenteral litholysis of the drug trometamol N and metaphylaxis with biologically active additives prolit and urisan; 19 patients of group 2 have undergone extracorporeal shock-wave lithotripsy with parenteral litholysis and metaphylaxis by using biologically active additives prolit septo and urisan. Positive results were achieved in all the patients. In group 1 the concrements dissolved completely. In group 2 small fragments up to 4 mm eliminated after partial solution.

[Treatment and metaphylaxis of gout complicated by nephropathy and urolithiasis].

The evaluation of clinical efficacy of combined treatment and metaphylaxis in 58 patients with gout complicated by nephropathy and urolithiasis was performed. The study included 41 (71%) men and 27 (29%) women aged 44 to 88 years (mean age - 58 +/- 7 years). All patients received parenteral therapy with trometamol H, 5 -10 infusion for the course, an average of 7 infusions. For the metaphylaxis, all patients received biologically active supplement urisan 2 tablets 2 times a day during next three months against the background of drug therapy. Findings indicate a high clinical efficacy of the trometamol H in the combined treatment of patients with gout, complicated by nephropathy and urolithiasis, considering that improvement of renal function, microcirculation in the renal parenchyma, increased glomerular filtration rate, normalization of nitrogenous wastes levels, partial or complete dissolution of concretions of the kidneys, a significant decrease in the tophs size, an increase in motor activity were observed, which ultimately improves the quality of life for these patients. Metaphylaxis using urisan for 3 months on a background of traditional therapy contributed to a stable normalization of blood uric acid levels, which prevented the exacerbation of underlying disease and recurrent stone formation. These data allow to recommend reducing the dose of traditional anti-gout drugs and conducting repeated course of metaphylaxis with the urisan after 5-6 months during 3 months.

[Food additive urisan in combined treatment of urolithiasis].

Thirty three urolithiasis patients (13 males, 18 females aged 29-77 years, 2 children, duration of the disease 1-17 years) received food additive urisan in combined treatment of urolithiasis. Blood and urine biochemistry was studied by 11 parameters to evaluate renal function and lithogenesis before and after intake of urisan. Standard treatment was combined with intake of 2 capsules (1100 mg) of urisan twice a day at meal for 2-3 weeks. The data were processed statistically. It is shown that urisan contributes to intensification of renal filtration function, to reduction of hyperuricemia and urine pH, intensification of uric acid excretion, continuation of inflammation remission, attenuation of proteinurea in urolithiasis patients with exacerbation of chronic pyelonephritis.

Kinetic model of drug distribution in the urinary bladder wall following intravesical instillation.

Intravesical administration of cytotoxic agents is commonly used in urological practice for treatment of superficial bladder cancer. The leading motive is optimisation of drug delivery near the site of action and reduction of systemic toxicity. Bladder pharmacokinetics is complicated by several mechanisms. The objectives of this work were to develop a kinetic model of drug distribution in the bladder wall following intravesical instillation and to study the effect of various parameters on tissue and systemic drug exposure and explore the potential benefits of permeability enhancing effects of chitosan (CH) and polycarbophil (PC) through simulation. Key elements of the model are variable urinary drug concentration due to urine formation and voiding, biphasic diffusion in the bladder tissue and systemic absorption. Model parameters were estimated from bladder-tissue concentration profiles obtained in previous in vitro experiments with pipemidic acid (PPA) as a model drug. The results support further investigations on application of CH and PC in intravesical drug delivery. Both polymers increase permeability of the bladder wall by diffusion enhancement in the urothelium and presumably by improving the contact with the bladder surface. The developed mathematical model could serve for optimisation of intravesical drug delivery and future development of intravesical drug delivery systems.

The influence of stirring rate on biopharmaceutical properties of Eudragit RS microspheres.

Eudragit RS microspheres containing pipemidic acid, as a model drug, were prepared by the solvent evaporation method using an acetone/liquid paraffin solvent system. The aim of the work was to evaluate the influence of stirring rate on the average particle size, particle morphology, drug content and release kinetics, as well as the influence of particle size on microsphere morphology, drug content and release kinetics. Stirring rate has been found to significantly influence the average diameter of microspheres. The average diameter decreases as the stirring rate increases. This can be explained by production of a finer dispersion of droplets when higher stirring rates are applied and, consequently, by the formation of smaller microspheres. With increasing stirring rate and increasing fraction particle size the drug content also increases. It is assumed that this dependence is a consequence of an uneven diffusion of the drug from the inner to the outer emulsion phase, and an uneven encapsulation of drug particles during the preparation. Drug release follows the Higuchi model. As seen from SEM photographs, larger microspheres are more porous and the microspheres produced at higher stirring rates are more porous than those produced at lower stirring rates. This explains the unexpected finding that the release rate increases as the fraction particle size and the stirring rate increase.

The influence of magnesium stearate on the characteristics of mucoadhesive microspheres.

Microspheres containing the mucoadhesive polymer chitosan hydrochloride, with matrix polymer Eudragit RS, pipemidic acid as a model drug and agglomeration preventing agent magnesium stearate were prepared by the solvent evaporation method. The amount of magnesium stearate was varied and the following methods were used for microsphere evaluation: sieve analysis, drug content and dissolution determination, scanning electron microscopy, x-ray diffractometry, DSC and FTIR spectroscopy. The results showed that average particle size decreased with increasing amount of magnesium stearate used for microsphere preparation. This is probably a consequence of stabilization of the emulsion droplets with magnesium stearate. Higher pipemidic acid content in the microspheres was observed in larger particle size fractions and when higher amounts of magnesium stearate were used. It was also found that these two parameters significantly influenced the dissolution rate. The important reason for the differences in drug content in microspheres of different particle sizes is the diffusion of pipemidic acid from the acetone droplets in liquid paraffin during the preparation procedure. The physical state of pipemidic acid changed from crystalline to mostly amorphous with its incorporation in microspheres, as shown by x-ray diffractometry and differential scanning calorimetry. No differences were observed in the physical state of pipemidic acid and in microsphere shape and surface between different size fractions of microspheres, prepared with different amounts of magnesium stearate. Additionally, no correlation between the physical state of the drug in different microspheres and their biopharmaceutical properties was found.

[Urotractin in the treatment of an infection of the kidneys, urinary tract and prostate]. / Urotraktin v lechenii infektsii pochek, mochevykh putei i predstatel'noi zhelezy.

Clinical and bacteriological effects of urotractin are analysed for 60 patients with infectious-inflammatory diseases of the kidney, urinary tracts and prostate treated in 3 urological clinics of Moscow. The drug was given 10 days in a dose 400 mg twice a day. Urotractin demonstrated high efficacy against both gram-negative and gram-positive bacteria. The results were the same in in- and outpatients.

Padräo de resistência a quinolonas de amostras multiresistentes de Staphylococcus aureus de origem hospitalar / The resistance pattern to quinolones with 12 staphylococcus aureus multiresistance samples from hospitals

Foi realizado um estudo do padräo de resistência às quinolonas em amostras de staphylococcus aureus oxacilina resistentes (ORSA) isoladas de pacientes internos no Hospital Universitário "Lauro Wanderley" (HU/UFPb). Utilizando 12 amostras bacterianas caracterizadas fenotipicamente em termos de identificaçäo, sorologia, triagem em agar e teste de sensibilidade aos microbianos utilizando-se as seguintes quinolonas: ácidos nalidíxico, ácido pipemídico, norfloxacin, pefloxacin, ciprofloxacin, lomefloxacin e ofloxacin. Os resultados demonstraram que das 12 amostras de ORSA a maioria foi proveniente da Clínica Cirúrgica 08/12 (66,8 por cento), e relacionando o isolamento bacteriano ao sítio anatômico verificou-se que houve a predominância de amostras clínicas provenientes de ferida cirúrgica 07/12 (58,3 por cento). Com relaçäo ao teste de sensibilidade às drogas, verificou-se uma média de resistência de 53,0 por cento. Entre as quinolonas testadas às quais as bactérias apresentaram maior índice de sensibilidade destacam-se: Oflaxacin (83,3 por cento), Ciprofloxacin e Lomefloxacin (75,0 por cento), e Pefloxacin (58,3 por cento). Enquanto as que apresentaram menor eficácia foram: Nalidíxico (8,4 por cento) e Pipemídico (16,7 por cento)

[Single oral dose of phosphomycin trometamol versus pipemidic acid and norfloxacin in treating uncomplicated low-level urinary tract infections]. / Fosfomicina trometamol en dosis oral única versus ácido pipemídico y norfloxacino en el tratamiento de las infecciones urinarias bajas no complicadas.

OBJECTIVE: To make an assessment of the effectiveness and safety of a single oral dose compared with the conventional way of treating low-level Urinary Infections presenting no complications. DESIGN: This was an investigative and prospective study, using a control, a simple blind and randomised sample. SITE. Health Centres in Oviedo and Zaragoza. PATIENTS OR OTHERS PARTICIPANTS: We looked at 150 patients and included 106 females between the ages of 16 and 75 in the study. Their clinical symptoms were compatible with low-level urinary infections presenting no complications. INTERVENTIONS: 49 patients were given Trometamol Phosphomicine (TP) in a single oral dose; 36 took Pipemidic Acid (PA) and 21 Norfloxacine (NFX), both of these in a dose of 400 mg twice a day for 5 to 7 days. MAIN MEASUREMENTS AND RESULTS: Clinical and bacteriological assessments of the results were made 3, 7, and 28 days after treatment. A total of 75 gems were isolated: E. coli was the most common (68%). In all three groups, the main symptoms rapidly disappeared after the start of the treatment. CONCLUSIONS: Having considered the bacteriological and clinical findings, as well as tolerance levels, we are able to conclude that a single oral dose of Trometamol Phosphomicine is a good alternative to conventional therapy for the treatment of low-level Urinary Infections Which present no complications.

Fixed drug eruption due to pipemidic acid.

A 71-year-old woman with fixed drug eruption caused by pipemidic acid is reported. The patient developed typical lesions on rechallenge with pipemidic acid, but not with nalidixic acid, an analogue of pipemidic acid.

Pharmacokinetics of pipemidic acid in chickens after single intravenous and oral dosings.

The pharmacokinetics of pipemidic acid after 2 single doses were studied in broiler chickens. Chickens were given single IV and oral doses of 10 and 30 mg of pipemidic acid/kg of body weight. Blood samples were collected over 8 hours after each dose administration. High-pressure liquid chromatography with UV detection was used to determine concentrations in plasma of pipemidic acid. The plasma concentration-time curves after IV administration followed 2-compartment characteristics, rapid initial distribution phase, and a terminal elimination phase. The pharmacokinetic variables differed significantly between single doses of 10 and 30 mg of pipemidic acid/kg. Mean disposition variables were a half-life at alpha phase of 0.06 hours or 0.33 hours, a half-life at beta phase of 1.18 hours or 1.72 hours, a volume of distribution in the central compartment of 0.12 L/kg or 0.31 L/kg, a volume of distribution during the elimination beta phase of 1.64 L/kg or 1.05 L/kg, and a total plasma clearance of 0.97 L/h.kg or 0.41 L/h.kg, for the 10 or 30 mg/kg dose, respectively. After oral administration, the pipemidic acid plasma profile could be adequately described by a 1-compartment model. After the single oral doses of 10 and 30 mg of pipemidic acid/kg, pipemidic acid was absorbed rapidly (time to maximal concentration of 0.31 hours or 0.71 hours) and eliminated with a mean half-life of 0.86 hours or 0.61 hours, respectively. The bioavailability was 39% at 10 mg of pipemidic acid/kg and 61% at 30 mg of pipemidic acid/kg.

A general practitioner multicenter study: fosfomycin trometamol single dose versus pipemidic acid multiple dose.

In order to evaluate the efficacy and safety of fosfomycin trometamol as single dose oral treatment for acute cystitis in women, an open, multicenter comparative study was carried out in general practices in France, 386 women, aged 16 to 75 years, with clinical symptoms of acute cystitis were enrolled in the study to receive either a single 3 g oral dose of fosfomycin trometamol or a five-day course of 400 mg pipemidic acid twice daily. The diagnosis of cystitis was based on clinical symptoms and significant bacteriuria (greater than or equal to 10(5) cfu/ml midstream urine). Follow-up examinations were carried out five to ten and 28 days after the end of treatment, 289 and 244 patients, respectively, were available for clinical and bacteriological evaluation at short-term (five to ten days) and medium-term (28 days) post-treatment follow-up. Both regimens were comparable for clinical and bacteriological efficacy with short-term eradication rates of 122/146 in the fosfomycin trometamol group and 130/143 in the pipemidic acid group. The results of medium-term follow-up were 113/122 and 114/122 for the eradication rates of the respective groups. Both drugs were well tolerated. Side effects were mild and of significantly shorter duration in the fosfomycin trometamol group.

Fosfomycin trometamol versus pipemidic acid in the treatment of bacteriuria in pregnancy.

The Italian multihospital study of bacteriuria in pregnancy randomized 153 pregnant bacteriuric patients to receive fosfomycin trometamol (FT) as a single dose of 3 g and 138 such patients to receive conventional therapy with pipemidic acid (PA), 400 mg b.i.d. for seven days. The two groups were well matched for age, parity, pregnancy course, symptoms and past history of cystitis. Infecting organisms were eradicated in 147 (96%) of FT and 129 (94%) of PA patients. Similar recurrence rates occurred. Minimal side effects (mostly nausea and dyspepsia) occurred (9%) FT; 15% PA). Single-dose FT appeared equivalent to conventional treatment with PA.

[Preventive treatment of recurrent essential cystitis in women. Comparative study of pipemidic acid and placebo in a daily dose of 200 mg. for 6 months]. / Traitement préventif de la cystite essentielle récidivante de la femme. Etude comparative de l'acide pipémidique contre placebo en prise quotidienne de 200 mg pendant 6 mois.

Seventy female patients presenting with frequent (less than or equal to 4 episodes per year) recurrent essential cystitis participated in a comparative, double-blind placebo-controlled study of prophylactic treatment with Pipram. Treatment was administered at the dose of 200 mg in the evening at bedtime for 6 months, followed by a post-treatment phase of 6 months. Four episodes of cystitis occurred during the first 6 months in the Pipram group and 11 in the placebo group; a single episode of infection was observed in the placebo group over the entire observation period (1/2 year). The difference between the two groups, Pipram and placebo, was statistically significant at 6 months and at 1 year. The relative risk of infection in the placebo group was 3.02 at 6 months and 3.56 at 12 months. The bacteria responsible for reinfection during and after treatment were resistant to pipemidic acid in 2 out of 2 cases in the Pipram group and in 2 out of 7 cases in the placebo group. Treatment was well tolerated: 2 discontinuations of treatment because of benign side effects in the Pipram group.

Treatment of experimental cystitis in the rat with a single dose of fosfomycin trometamol.

The therapeutic effectiveness of a single oral dose (60 and 200 mg/kg body weight) of fosfomycin trometamol (FT), norfloxacin, trimethoprim sulfamethoxazole (Bactrim) and pipemidic acid against experimental cystitis in the rat were compared. Infections were produced with clinical isolates of Klebsiella pneumoniae, Proteus mirabilis and Escherichia coli in a total of 135 Sprague-Dawley albino rats. Oral treatment with all four drugs consistently lowered the numbers of CFU in bladder tissue, especially E. coli and P. mirabilis. Fosfomycin trometamol appeared to be as effective as norfloxacin for treatment of E. coli cystitis even thoughs its minimal inhibitory concentration (MIC) in vitro is 100 times greater than that of the quinolonic antibiotic. Fosfomycin trometamol, pipemidic acid and Bactrim were equally effective against P. mirabilis infection, but FT was less active than norfloxacin or Bactrim for treatment of K. pneumonia cystitis. In conclusion, single dose treatment with fosfomycin trometamol was effective for treatment of experimental cystitis in the rat and might, by extrapolation, be of use in clinical practice for single dose treatment of uncomplicated urinary tract infections.