Ethylcellulose inserts of an orphan drug for periodontitis: preparation, in vitro, and clinical studies.

Ethylcellulose inserts of niridazole fabricated by casting were studied for in vitro release and in vivo clinical effectiveness. The in vitro drug release was steady and sustained for over 7 days and followed diffusion kinetics. Selected batch, EN3, was evaluated clinically in patients with periodontitis for 6 months. A significant improvement (alpha < or = 0.05) in clinical indices from baseline was observed. Intergroup study revealed a significant (alpha < or = 0.01) change in the bleeding index, gingival index, plaque index, calculus criteria, and pocket depth. Significant reduction in total bacterial count in gingival crevicular fluid was observed before and postdevice insertion, as well as between control and treatment groups.

Niridazole biodegradable inserts for local long-term treatment of periodontitis: possible new life for an orphan drug.

Periodontal pocket inserts of niridazole (NZ) made with Resomer(R) (grades RG 503H and RG858, designated as RH and RG, respectively) were studied. Various formulation variables were evaluated to obtain a biodegradable delivery systems showing device degradation and drug depletion parallel to each other in vitro. Drug release from the prepared inserts was evaluated using a static dissolution setup (for 1 month). Incorporation of 3 parts of RG in 1 part of RH inserts caused a 50% decrease in the initial release rate. The RH-NZ inserts showed a spurt in release around the 10th day of the study, which coincided with the decrease in device weight, suggesting onset of device degradation. Pilot-scale clinical trials in 12 patients indicated improvements in clinical indices from the baseline values. The average pocket depth was reduced significantly (alpha = 0.05) from 6.34 +/- 1.86 mm at baseline to 5.94 +/- 0.28 mm after 28 days of treatment.

In pursuit of drugs for American trypanosomiasis: evaluation of some "standards" in a mouse model.

Forty-nine "standard" compounds known to be useful in the treatment of other diseases were tested for their suppressive activity against the trypomastigotes of Trypanosoma cruzi-infected mice. The most active was the antidepressant protriptyline, which was almost three times as effective as the reference drug, nifurtimox. A major value of the present data is to demonstrate the refractoriness of the T. cruzi parasite against many of the drug standards that have known biological activity.

Prevalence and intensity of Schistosoma haematobium urinary schistosomiasis in the Port St Johns district.

A urinary schistosomiasis survey undertaken in the Port St Johns district of the former Transkei showed the parasite to be endemic and noted an increase in overall infection rates in the region compared with previous studies. There was a general stability in infection over the sampling period 1987-1989. Prevalence rates were low to moderate with an overall prevalence of 42%. These ranged from approximately 10% in the low-prevalence settlement to 89.9% in the settlement with the highest prevalence. Infection rates were found to decrease nearer the coast, and settlements closest to the sea had the lowest prevalence rates. The intensity of infection was low, with the majority of patients having fewer than 200 eggs per 10 ml urine. Very few sufferers were treated with Ambilhar at clinics and hospitals.

Pregnancy following infertility due to pelvic schistosomiasis--a case report.

A case of infertility due to bilateral tubal blockage secondary to pelvic schistosomiasis in a Nigerian woman is presented. Intra uterine pregnancy followed treatment by peritubal adhesiolysis and the use of niridazole.

[Treatment of bilharziasis]. / Le traitement des bilharzioses.

Specific treatment of bilharziosis is obviously simplified by praziquantel which, unfortunately, is not easily available in endemic areas. Nevertheless, the major problem is an early treatment before the occurrence of severe sequellae. Mass chemoprophylaxis remains needed and, if possible, with praziquantel. For economic purposes, we have often to use either oxamniquine or niridazole-metrifonate combination.

Autoradiographic quantification of the efficacy of niridazole in mice infected with 75Se-labelled cercariae of Schistosoma mansoni.

The effects of the anti-schistosomal drug, niridazole, on the migration of Schistosoma mansoni larvae, biosynthetically radioisotope-labelled with 75[Se]-selenomethionine, was evaluated by autoradiography of compressed tissues of mice treated daily from Days 6 to 10 post-infection with 200 mg kg-1 niridazole. The results were compared with the migration of schistosomula in untreated controls. The distribution of schistosomula was altered in niridazole-treated mice, where there was a delayed migration from the lungs relative to the controls and significantly fewer schistosomula in total appeared to reach the liver. The total percentage of schistosomula detected as autoradiographic foci was significantly lower in treated mice than in the untreated controls. Niridazole-treated mice were free of any foci 10 days after the last treatment and no adult worms were recovered on perfusion of the hepatic portal system relative to control mice from which 5.8% of the infective cercariae were recovered as adult worms at Day 42 post-infection.

Schistosoma haematobium: histochemistry of glycogen, glycogen phosphorylase a and glycogen branching enzyme in niridazole-treated females.

The body posterior to the ovary of Schistosoma haematobium females was investigated. Glycogen, glycogen phosphorylase a (EC 2.4.1.1) and glycogen branching enzyme (EC 2.4.1.18) activities were detected in the subtegumental muscle system, parenchyma and mature vitelline cells, whereas no activities were detected in the tegument and immature vitelline cells of the parasite. Administration of a single niridazole dose of 250 mg kg-1 to the pouched mouse (Saccostomus camestris) produced the following changes in S. haematobium females: a relatively rapid depletion of glycogen stores due to disruption of the absorptive surface of the parasite, and to an increase in the activity of glycogen phosphorylase a; a reduction in the phosphorylase a to phosphorylase b-conversion capacity of glycogen phosphorylase phosphatase (EC 3.1.3.17); a decrease in glycogen branching enzyme activity; and a relatively rapid degeneration of parasite cells possibly due to their loss of endogenous energy reserves.

Comparative trials of regimes for the treatment of urinary schistosomiasis in The Gambia.

Alternative regimes for the treatment of Schistosoma haematobium infection were compared in two trials. Praziquantel at a dose of 40 mg kg-1 appeared to cure 63% of a random sample of heavily infected subjects; significantly more than the 18% cured by three fortnightly doses of metrifonate at 10 mg kg-1. However, praziquantel led to a greater incidence of mild, transient side-effects. A single dose of metrifonate was found to be an inadequate treatment in the same group of subjects as it left 53% with an egg count of at least 100 ova/10 ml. A combination of 10 mg kg-1 of metrifonate and 25 mg kg-1 of niridazole had a similar effect to that of a single dose of metrifonate alone and it had more side-effects. Reduced doses of praziquantel had less effect on egg counts than the standard regime, but the difference was not significant in the case of 20 mg kg-1. Although a combination of metrifonate and praziquantel, each at 10 mg kg-1, had a greater effect than either constituent alone, the difference was not significant. Factors affecting the choice of drug for use in mass treatment of urinary schistosomiasis in The Gambia are discussed. The present findings suggest that the standard regime of praziquantel should be used or, if this is not possible, a three-dose metrifonate regime.

Conservative management of surgical acute renal failure due to schistosomiasis. A case report.

A patient with schistosomiasis-induced acute renal failure is presented. She responded dramatically to peritoneal dialysis and niridazole (Ambilhar; Ciba). In a centre with more sophisticated facilities, early surgical intervention would have been considered. A search of the English-language literature has not revealed a patient with similar presentation and management.

Polycythaemia following renal transplantation: an association with azathioprine dosage?

Patients from a renal transplantation unit with an unusually high incidence of polycythaemia were divided into polycythaemic and control groups. The rate of rise of haemoglobin concentration was not significantly different in the two groups. The polycythaemic group received a significantly lower dose of azathioprine (p less than 0.005) and included more patients with polycystic disease than the control group (p less than 0.05). An effect of azathioprine on bone marrow function was suggested by the polycythaemic group also having a higher mean white cell count (p less than 0.02). Azathioprine dosage correlated negatively with post-transplantation polycythaemia regardless of the original cause of renal failure.

[Kinetics of the antibody level in schistosomiasis under chemotherapy]. / Zur Kinetik des Antikörperspiegels bei Schistosomiasis unter Chemotherapie.

The antibody level (ELISA) in schistosomiasis much increased one month after therapy. The sanation of the parasitosis within 6 months led to the reduction of the values to the initial level without any further later decrease. The antibody kinetics was the same after successful Niridazol and Praziquantel treatment. When Niridazol failed a second treatment with Praziquantel led to a repeated significant increase. The decrease after the second peak was much steeper and obtained the initial level already 3 months after sanation. Patients with falsely negative ELISA before the treatment reacted partly positive one month after this. One third of all patients examined reacted negatively also at this time. Falsely positive findings in patients from endemic areas (specificity 0.74) seem to be no cross reaction to another affection with helminths, but seem to be traced back to an earlier inapparent schistosomiasis.

Schistosoma mansoni: chemotherapy of infections of different ages.

Mice were treated with potassium antimony tartrate, hycanthone, oxamniquine, niridazole, or praziquantel at different times after infection with Schistosoma mansoni. The rate of cure was assessed by perfusion of surviving worms approximately 4 weeks after treatment, and the percentage reduction in worm burden was estimated relative to the number of adult worms perfused from control mice, comparably infected but untreated. All six drugs were relatively inactive against S. mansoni between 3 and 4 weeks after infection when compared with treatment at 5 to 6 weeks. However, the drugs differed in the patterns of cure they achieved in the 2-week period after administration of cercariae and in the period around the onset of patency. Worms that had been subjected to amoscanate or hycanthone in the third week after infection showed evidence of this as adults in having a reduced fecundity. Factors such as worm or host physiology, or host immune status may have had roles in the outcome of chemotherapy at different stages of maturation of S. mansoni.

Schistosomiasis and renal transplantation.

Schistosomiasis was discovered in 4 recipients and 12 donors during evaluation for 67 consecutive live related renal transplants. All participants with schistosomiasis were treated with anti-schistosomal chemotherapy preoperatively. No complications were seen in the 4 recipients, including 2 with schistosomal-induced calcifications of the bladder. One donor returned to an endemic area and became reinfected with slight progression of distal ureteral dilatation. Cystoscopy with biopsy is more sensitive in the detection of infection than ultrasonography, excretory urography or urinalysis but structural changes are assessed by excretory urography. Although schistosomiasis is not an absolute contraindication for renal transplantation, potential live kidney donors with proved anatomical changes in the urinary tract should be excluded.