Transactions of The Royal Society of Tropical Medicine and Hygiene, Mar 1, 1990
The effect of praziquantel in different concentrations on isolated rat hepatocytes as a cellular ... more The effect of praziquantel in different concentrations on isolated rat hepatocytes as a cellular target was studied to detect any possible toxicity. Leakage of cytosolic enzymes, aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase (LDH) was monitored after one hour of incubation of all the cells with the drug. Levels of reduced glutathione (GSH) and cytochrome P450 were also assayed. The drug, in concentrations of 5, 25, 50 and 100 yg/ml, had no effect on any of these parameters. In contrast, the hepatotoxic compound trichloroethylene showed dose-dependent toxicity, as measured by trypan blue (TB) exclusion, LDH leakage, and reduction in GSH content in the present cellular model. These results suggest that praziquantel is a relatively safe drug with respect to liver function.
Transactions of The Royal Society of Tropical Medicine and Hygiene, 1989
Combined low doses of praziquantel and oxamniquine were tested against different stages of Schist... more Combined low doses of praziquantel and oxamniquine were tested against different stages of Schistosoma munsoni in infected Swiss albino mice. The effect of combination therapy (ti the curative dose of praziquantel plus s the curative dose of oxamni-. quine) was compared with the effect of each drug alone, in reduced or full dose. Comparison with infected untreated controls was also made. Drug effects were evaluated on different growth stages of schistosomes by administering the drugs 24 h before infection and b h, 1, 2, 3; 4 and 3 weeks after infection. Animals were killed 8 weeks after infection. Worm burden, distribution, tissue egg load and oogram pattern were used in assessing drug efficacy. A potentiating effect was observed in animals receiving combination therapy. The combination regimen was most effective 4 h after infection, producing 96% worm reduction; eggs were not detected in the liver or intestine. Five weeks after infection the same regimen resulted in 98% reduction in the tissue egg load.
The immunopharmacological properties of praziquantel were studied in mice infected with Schistoso... more The immunopharmacological properties of praziquantel were studied in mice infected with Schistosoma mansoni. Hepatic granuloma measurement was the main parameter of assessment. Delayed foot pad swelling as an in vivo correlate for the delayed granulomatous hypersensitivity reaction was also determined. Fluorescent direct antigen-antibody reaction in the granuloma together with the immediate foot pad swelling were used to test for the humoral immune response. Praziquantel administered at seven weeks after infection in two dose regimens (3 X 250 mg kg-1 for three consecutive days and 3 X 83 mg kg-1 given four hourly within the same day was more or less equally effective in reducing the size of hepatic granuloma by 37-41% two weeks after treatment and by 81-85% one month after treatment. Delayed foot pad swelling using soluble egg antigen (SEA) was significantly suppressed one month after treatment by 53%. At nine weeks after infection the fluorescent antigen-antibody reaction in the granuloma was positive in the untreated controls, but at the same time (i.e. two weeks after treatment) it was negative in the praziquantel-treated mice. One month after treatment positivity was less compared to infected control mice. Reduction in worm burden, hepatic shift of the worms and the reduced number of ova per gram of tissue denoted the efficacy of the drug in its two dose regimens against the Egyptian strain of S. mansoni.
Antimicrobial Agents and Chemotherapy, Jun 1, 2015
Consideration of existing compounds always simplifies and shortens the long and difficult process... more Consideration of existing compounds always simplifies and shortens the long and difficult process of discovering new drugs specifically for diseases of developing countries, an approach that may add to the significant potential cost savings. This study focused on improving the biological characteristics of the already-existing antischistosomal praziquantel (PZQ) by incorporating it into montmorillonite (MMT) clay as a delivery carrier to overcome its known bioavailability drawbacks. The oral bioavailability of a PZQ-MMT clay nanoformulation and its in vivo efficacy against Schistosoma mansoni were investigated. The PZQ-MMT clay nanoformulation provided a preparation with a controlled release rate, a decrease in crystallinity, and an appreciable reduction in particle size. Uninfected and infected mice treated with PZQ-MMT clay showed 3.61-and 1.96-fold and 2.16-and 1.94fold increases, respectively, in area under the concentration-time curve from 0 to 8 h (AUC 0-8) and maximum concentration of drug in serum (C max), with a decrease in elimination rate constant (k el) by 2.84-and 1.35-fold and increases in the absorption rate constant (k a) and half-life (t 1/2e) by 2.11-and 1.51-fold and 2.86-and 1.34-fold, respectively, versus the corresponding conventional PZQ-treated groups. This improved bioavailability has been expressed in higher efficacy of the drug, where the dose necessary to kill 50% of the worms was reduced by >3-fold (PZQ 50% effective dose [ED 50 ] was 20.25 mg/kg of body weight for PZQ-MMT clay compared to 74.07 mg/kg for conventional PZQ), with significant reduction in total tissue egg load and increase in total immature, mature, and dead eggs in most of the drug-treated groups. This formulation showed better bioavailability, enhanced antischistosomal efficacy, and a safer profile despite the longer period of residence in the systemic circulation. Although the conventional drug's toxicity was not examined, animal mortality rates were not different between groups receiving the test PZQ-clay nanoformulation and conventional PZQ.
Context: Calotropis procera (Ait.) R. Br. (Asclepiadaceae), Ficus elastica Roxb. (Moraceae) and Z... more Context: Calotropis procera (Ait.) R. Br. (Asclepiadaceae), Ficus elastica Roxb. (Moraceae) and Zingiber officinale Roscoe (Zingiberaceae) have been traditionally used to treat many diseases. Objective: The antischistosomal activity of these plant extracts was evaluated against Schistosoma mansoni. Materials and methods: Male mice exposed to 80 AE 10 cercariae per mouse were divided into two batches. The first was divided into five groups: (I) infected untreated, while groups from (II-V) were treated orally (500 mg/kg for three consecutive days) by aqueous stem latex and flowers of C. procera, latex of F. elastica and ether extract of Z. officinale, respectively. The second batch was divided into four comparable groups (except Z. officinale-treated group) similarly treated as the first batch in addition to the antacid ranitidine (30 mg/kg) 1 h before extract administration. Safety, worm recovery, tissues egg load and oogram pattern were assessed. Results: Calotropis procera latex and flower extracts are toxic (50-70% mortality) even in a small dose (250 mg/kg) before washing off their toxic rubber. Zingiber officinale extract insignificantly decrease (7.26%) S. mansoni worms. When toxic rubber was washed off and ranitidine was used, C. procera (stem latex and flowers) and F. elastica extracts revealed significant S. mansoni worm reductions by 45.31, 53.7 and 16.71%, respectively. Moreover, C. procera extracts produced significant reductions in tissue egg load ($34-38.5%) and positively affected oogram pattern. Conclusion: The present study may be useful to supplement information with regard to C. procera and F. elastica antischistosomal activity and provide a basis for further experimental trials.
The aggressive use of praziquantel to combat schistosomiasis in Egpyt raises concern about the po... more The aggressive use of praziquantel to combat schistosomiasis in Egpyt raises concern about the possible emergence of resistance. Eggs from Egyptian patients with praziquantel-resistant infections (not cured by 3 doses of praziquantel) have been used to establish infection-specific schistosome isolates in mice. The response of these worms to the drug was observed in vitro, in order to determine if the isolates obtained from these resistant infections were, in fact, less responsive to praziquantel. One of the hallmark effects of praziquantel on schistosomes in vitro is a disruption of the worm's outer surface, the tegument. Here, praziquantel-induced tegumental damage is observed in 3 distinct isolates, 2 derived from resistant infections and 1 from an infection cured by a single dose. The isolates from the resistant infections were less susceptible to praziquantel-induced tegumental damage in vitro, suggesting that the worms are in some way less responsive to the drug.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
International Journal for Parasitology: Drugs and Drug Resistance, 2019
We report the evaluation of 265 compounds from a PDE-focused library for their antischistosomal a... more We report the evaluation of 265 compounds from a PDE-focused library for their antischistosomal activity, assessed in vitro using Schistosoma mansoni. Of the tested compounds, 171 (64%) displayed selective in vitro activity, with 16 causing worm hypermotility/spastic contractions and 41 inducing various degrees of worm killing at 100 μM, with the surviving worms displaying sluggish movement, worm unpairing and complete absence of eggs. The compounds that did not affect worm viability (n = 72) induced a complete cessation of ovipositing. 82% of the compounds had an impact on male worms whereas female worms were barely affected. In vivo evaluation in S. mansoni-infected mice with the in vitro 'hit' NPD-0274 at 20 mg/kg/day orally for 5 days resulted in worm burden reductions of 29% and intestinal tissue egg load reduction of 35% at 10 days posttreatment. Combination of praziquantel (PZQ) at 10 mg/kg/day for 5 days with NPD-0274 or NPD-0298 resulted in significantly higher worm killing than PZQ alone, as well as a reduction in intestinal tissue egg load, disappearance of immature eggs and an increase in the number of dead eggs.
While surveillance cameras are a powerful tool for the prevention, detection and resolving of cri... more While surveillance cameras are a powerful tool for the prevention, detection and resolving of crimes, for most cases the amount of video data has become unmanageable. To ease the analysis, various automatic methods have been proposed, focusing on data-management, detecting suspicious behavior, person recognition, or event reconstruction. In this paper we focus on event reconstruction, in particular on tracing the whereabouts of people. The standard approach for such event reconstruction is to first detect persons in single frames and then match a query to all detections to retrieve the same person in multiple cameras. However, since the number of detected persons is large and performance of matching techniques limited, this process is slow and prone to errors. Intelligent interactive techniques are urged for. We propose to represent detected persons by their complete track within a single camera instead of a single detection and thereby reduce the search-space. On these tracks we use Relevance Feedback to improve recall with only a small effort of the user. Testing the tracking method on a benchmark dataset and a real-life dataset led to a reduction of the search space of 90%, while tracing accuracy based on the distance between tracks improved recall by up to 110% when compared to random tracing. Adding Relevance Feedback led to an additional improvement in recall of up to 400% compared to sequential scanning using the same number of visual assessments.
Background: Schistosomiasis is responsible for a considerable global disease burden. This work ai... more Background: Schistosomiasis is responsible for a considerable global disease burden. This work aimed to improve the therapeutic outcome of the only available antischistosomal drug worldwide, praziquantel (PZQ), by incorporating it into a novel carrier, "solid lipid nanoparticles (SLNs)", to enhance its solubility, bioavailability and efficacy. A simple, cost-effective method was used to prepare SLN-PZQ. Results: Compared to market PZQ (M-PZQ), SLN-PZQ was more bioavailable, as denoted by higher serum concentrations in both normal and infected mice where elevated K a , AUC 0-24 , C max , and t 1/2e with a decrease in k el were demonstrated. The AUC 0-24 for SLN-PZQ in normal and Schistosoma mansoni-infected groups was almost nine-and eight-fold higher, respectively, than that for M-PZQ in corresponding groups. In normal and S. mansoni-infected mice, SLN-PZQ was detectable in serum at 24 h, while M-PZQ completely vanished 8 h post-treatment. Additionally, enhanced absorption with extended residence time was recorded for SLN-PZQ. Compared to M-PZQ, SLN-PZQ revealed superior antischistosomal activity coupled with enhanced bioavailability in all treated groups where higher percentages of worm reduction were recorded with all dosages tested. This effect was especially evident at the lower dose levels. The ED 95 of SLN-PZQ was 5.29-fold lower than that of M-PZQ, with a significantly higher reduction in both the hepatic and intestinal tissue egg loads of all treated groups and almost complete disappearance of immature deposited eggs (clearly evident at the low dose levels). Conclusions: SLN-PZQ demonstrated enhanced PZQ bioavailability and antischistosomal efficacy with a safe profile despite the prolonged residence in the systemic circulation.
Cytophotometric measurement of the effect of praziquantel (500 mg/kg for 2 days) versus hycanthon... more Cytophotometric measurement of the effect of praziquantel (500 mg/kg for 2 days) versus hycanthone (60 mg/kg for 3 days) on hepatocyte nuclear deoxyribonucleic acid (DNA) content was evaluated in Schistosoma mansoni infected mice. Drugs were given 8 weeks post-infection and repeated weekly for 4 weeks. DNA values of infected untreated control and infected drug treated groups were related to the median and upper diploid DNA values of normal control. Schistosoma mansoni infection per se did not change the hepatocyte DNA content, yet aneuploidy was 16. 7%. Praziquantel did not result in significant change of DNA content or ploidy, while hycanthone resulted in marked significant increase of DNA content (328. 9%) and aneuploidy (100%), compared to infected untreated control. Histopathological examination revealed hyperchromatic nuclei with mitosis in the hepatocytes of hycanthone treated mice, but not in praziquantel treated animals. These DNA changes were found to correlate with the reported safety of praziquantel and the carcinogenicity of hycanthone. KEY wokos: hepatocyte DNA, schistosomicidal drugs.
Journal of advanced pharmaceutical technology & research, 2016
Resveratrol is a naturally occurring polyphenol, possesses several pharmacological activities inc... more Resveratrol is a naturally occurring polyphenol, possesses several pharmacological activities including anticancer, antioxidant, antidiabetic, antinociceptive, and antiasthmatic activity. Little is known about its hepatoprotective action mechanisms. This study was conceived to explore the possible protective mechanisms of resveratrol compared with the hepatoprotective silymarin in thioacetamide (TAA)-induced hepatic injury in rats. Thirty-two rats were equally divided into four groups; normal control (i), TAA (100 mg/kg) (ii), TAA + silymarin (50 mg/kg) (iii), and TAA + resveratrol (10 mg/kg) (iv). Liver function and histopathology, pro-inflammatory cytokines, oxidative stress, and apoptotic markers were examined. Data were analyzed using ANOVA test followed by Tukey post hoc test. Compared to TAA-intoxicated group, resveratrol mitigated liver damage, and inflammation as noted by less inflammatory infiltration, hydropic degeneration with decreased levels of tumor necrosis factor-alpha, interleukin-6, and interferon-gamma by 78.83, 18.12, and 64.49%, respectively. Furthermore, it reduced (P < 0.05) alanine and aspartate aminotransferases by 36.64 and 48.09%, respectively, restored hepatic glutathione content and normalized superoxide dismutase and malondialdehyde levels. While it inhibited nuclear factor-kappa B, cytochrome 2E1, and enhanced apoptosis of necrotic hepatocytes via increasing caspase-3 activity. Our findings indicated that the potential hepatoprotective mechanisms of resveratrol are associated with inhibition of inflammation, enhancing the apoptosis of necrotic hepatocytes, and suppression of oxidative stress.
Results from infected patients, not cured by multiple doses of praziquantel (PZQ), have been repo... more Results from infected patients, not cured by multiple doses of praziquantel (PZQ), have been reported from different geographic locations, suggesting that resistance to the drug may be present. This has been coupled with several in vivo (e.g., studies on mice infected with &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;resistant isolates&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;) and in vitro tests (e.g., direct application and measurement of the effects of the drug on schistosomes maintained in culture) demonstrating a significant reduction in the drug&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s efficacy. Despite little field evidence that schistosomes are becoming less sensitive to the drug, 100% cure after PZQ is rarely achieved; meanwhile, the percentage of cure rates in endemic areas could be an overestimate if one accounts for the sensitivity of most egg counting methods coupled with the limited faecal sampling. To be proactive, the efficacy of PZQ has to be monitored on a systematic basis not only for cure, but also for the reduction of egg excretion complemented with periodical assessment for the susceptibility to the drug on local strains. Investigation of field isolates with confirmed diminished sensitivity to the drug will help in determining the frequency, epidemiology, genetic and physiologic basis for the observed resistance. Monitoring for changes in drug responsiveness in high transmission areas, where treatment failure as a result of immature or resistant parasites can not be differentiated, should be initiated. New chemotherapeutic alternatives and strategies in addition to a simple rapid, inexpensive test to detect resistance should be encouraged.
Transactions of The Royal Society of Tropical Medicine and Hygiene, 1986
Schistosoma mansoni egg granulomas were induced in the livers of mice by injecting eggs into sple... more Schistosoma mansoni egg granulomas were induced in the livers of mice by injecting eggs into spleens which had been surgically exposed with their vascular beds intact. Subsequent return of the spleens to a subcutaneous site allows repeated injections of eggs into the liver if necessary.
Murine schistosomiasis is usually associated with hepatic granulomatous lesions together with hig... more Murine schistosomiasis is usually associated with hepatic granulomatous lesions together with high serum and granuloma angiotensin converting enzyme (ACE) activity. Praziquantel (PRZ) which is known to reduce granuloma size was studied to show whether this effect is related to changes in ACE activity. Furthermore, captopril was studied to show whether by inhibiting ACE activity, the drug could also affect granuloma size. PRZ, captopril, and their combination led to significant reduction in liver granuloma. However, in normal mice, captopril was shown to increase rather than decrease serum ACE. The decrease in ACE activity by PRZ was correlated with its curative effect in infected mice. However, in experimentally induced pulmonary granulomata, the drug reduced granuloma size without affecting ACE activity of either serum or granuloma. It may be concluded that reduction in ACE activity may be beneficial as far as diminution of granuloma size is concerned and irrespective of whether there is an active infection or not. The possible use of Captopril as an antihypertensive in bilharzial infections associated with hypertension would probably not adversely affect the granulomatous lesions.
Journal of Traditional and Complementary Medicine, 2019
Few studies reported the antifibrotic effects of gallic acid (GA) despite its known hepatoprotect... more Few studies reported the antifibrotic effects of gallic acid (GA) despite its known hepatoprotective and antioxidant activities. Accordingly, this study investigated the antifibrotic effects of GA through clarifying its mechanisms on hepatic stellate cells' (HSCs) activation, proliferation and/or apoptosis. In vitro effects of GA on HSC-T6 activation/proliferation, morphology and safety on hepatocytes were assessed. In vivo, hepatic fibrosis was induced via chronic thioacetamide (TAA)-intoxication. TAA-intoxicated rats were treated with silyamrin or GA. At end of experiment, liver functions, hepatic MDA, GSH, PDGF-BB, TGF-b1, TIMP-1 and hydroxyproline were determined. Histological analysis and Sirius red staining of hepatic sections, expressions of alpha-smooth muscle actin (a-SMA), proliferating cellular nuclear antigen (PCNA) and caspase-3 were examined. In vitro, GA resulted in a concentration and time-dependent inhibition in HSCs activation, proliferation (IC 50 ¼ 45 and 19 mg/mL at 24 and 48 h respectively); restored the quiescent morphology of some activated HSCs plus its safety on hepatocytes. In vivo, GA reduced ALT, AST, MDA, PDGF-BB levels, collagen deposition and fibrosis score (S1 vs S4); increased caspase-3 expression and restored GSH stores, TGF-b1 level, a-SMA and PCNA expressions. In conclusion, GA counteracted the progression of hepatic fibrosis through reduction of HSCs proliferation/activation mutually with their apoptosis induction.
Context: Hibiscus sabdariffa L. (Malvaceae) is a common traditional tea that has many biological ... more Context: Hibiscus sabdariffa L. (Malvaceae) is a common traditional tea that has many biological activities. Objectives: To evaluate the hepatoprotective effect and study the metabolic profile of the anthocyaninrich extract of H. sabdariffa calyces (HSARE). Materials and methods: The hepatoprotective activity of HSARE was assessed (100 mg/kg/d for 4 weeks) by examining the hepatic, inflammatory, oxidative stress markers and performing a histopathological examination in rats with thioacetamide (TAA)-induced hepatotoxicity. HSARE was analyzed using ultra-performance liquid chromatography-quadrupole-time-of-flight-photodiode array-mass spectrometry (UPLC-qTOF-PDA-MS). Results: The UPLC-qTOF-PDA-MS analysis of HSARE enabled the identification of 25 compounds represented by delphinidin and its derivatives, cyanidin, kaempferol, quercetin, myricetin aglycones and glycosides, together with hibiscus lactone, hibiscus acid and caffeoylquinic acids. Compared to the TAAintoxicated group, HSARE significantly reduced the serum levels of alanine aminotransferase, aspartate aminotransferase and hepatic malondialdehyde by 37.96, 42.74 and 45.31%, respectively. It also decreased hepatic inflammatory markers, including tumour necrosis factor alpha, interleukin-6 and interferon gamma (INF-c), by 85.39, 14.96 and 70.87%, respectively. Moreover, it decreased the immunopositivity of nuclear factor kappa-B and CYP2E1 in liver tissue, with an increase in the effector apoptotic marker (caspase-3 positive cells), restoration of the altered hepatic architecture and increases in the activities of superoxide dismutase (SOD) and glutathione by 150.08 and 89.23%, respectively. Discussion and conclusion: HSARE revealed pronounced antioxidant and anti-inflammatory potential where SOD and INF-c were significantly improved. HSARE possesses the added value of being more water-soluble and of natural origin with fewer side effects expected compared to silymarin.
BMC International Health and Human Rights, Jul 27, 2012
A pool of 38 pan-African Centres of Excellence (CoEs) in health innovation has been selected and ... more A pool of 38 pan-African Centres of Excellence (CoEs) in health innovation has been selected and recognized by the African Network for Drugs and Diagnostics Innovation (ANDI), through a competitive criteria based process. The process identified a number of opportunities and challenges for health R&D and innovation in the continent: i) it provides a direct evidence for the existence of innovation capability that can be leveraged to fill specific gaps in the continent; ii) it revealed a research and financing pattern that is largely fragmented and uncoordinated, and iii) it highlights the most frequent funders of health research in the continent. The CoEs are envisioned as an innovative network of public and private institutions with a critical mass of expertise and resources to support projects and a variety of activities for capacity building and scientific exchange, including hosting fellows, trainees, scientists on sabbaticals and exchange with other African and non-African institutions.
The efficacy of two brands (brand 1 = Biltricide; Bayer AG, Leverkusen, Germany; brand 2 = Distoc... more The efficacy of two brands (brand 1 = Biltricide; Bayer AG, Leverkusen, Germany; brand 2 = Distocide; EPICO pharmaceuticals, Cairo, Egypt) of praziquantel (PZQ) in full and half doses (40 and 20 mg kg-1) monitored as percentage egg reduction and cure rate was investigated in S. mansoni infected school-children. A total of 506 school-children (8-16 years of age) were classified into three groups according to their intensity of infection, heavy [&amp;amp;gt; 500 eggs per grams (epg)], moderate (100-500 epg) and light (&amp;amp;lt; 100 epg), after examination three stool samples (three slides per sample) on three consecutive days. Percentage egg reduction and cure rate were monitored 4 and 10 weeks post-treatment for each dose regimen in the different test groups. Before testing the efficacy of either bran in patients, the pharmacokinetic parameters of the two brands were studied in non-infected normal volunteers. Statistical analysis of the pharmacokinetic parameters of brand 1 vs brand 2 (in a dose of 20 or 40 mg kg-1) revealed no significant difference in elimination (ke), absorption rate constant (ka), elimination half life (t1/2e), area under the time-concentration curve (Auc), serum maximum concentration (Cpmax) and time to maximum concentration (Tmax). As regards the efficacy of test drugs, statistical analysis revealed that up to 10 weeks post-treatment the two brands of PZQ in full dose were equally effective in reducing egg count as their half doses except in heavily infected cases treated with brand 2 of PZQ.(ABSTRACT TRUNCATED AT 250 WORDS)
Treatment with praziquantel (PZQ) has become virtually the sole basis of schistosomiasis control ... more Treatment with praziquantel (PZQ) has become virtually the sole basis of schistosomiasis control in sub-Saharan Africa and elsewhere, and the drug is reviewed here in the context of the increasing rate that it is being used for this purpose. Attention is drawn to our relative lack of knowledge about the mechanisms of action of PZQ at the molecular level, the need for more work to be done on schistosome isolates that have been collected recently from endemic areas rather than those maintained in laboratory conditions for long periods, and our reliance for experimental work mainly on Schistosoma mansoni, little work having been done on S. haematobium. There is no evidence that resistance to PZQ has been induced in African schistosomes as a result of its large-scale use on that continent to date, but there is also no assurance that PZQ and/ or schistosomes are in any way unique and that resistant organisms will not be selected as a result of widespread drug usage. The failure of PZQ to produce complete cures in populations given a routine treatment should therefore solicit considerable concern. With few alternatives to PZQ currently available and/or on the horizon, methods to monitor drug-susceptibility in African schistosomes need to be devised and used to help ensure that this drug remains effective for as long a time as possible.
Transactions of The Royal Society of Tropical Medicine and Hygiene, Mar 1, 1990
The effect of praziquantel in different concentrations on isolated rat hepatocytes as a cellular ... more The effect of praziquantel in different concentrations on isolated rat hepatocytes as a cellular target was studied to detect any possible toxicity. Leakage of cytosolic enzymes, aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase (LDH) was monitored after one hour of incubation of all the cells with the drug. Levels of reduced glutathione (GSH) and cytochrome P450 were also assayed. The drug, in concentrations of 5, 25, 50 and 100 yg/ml, had no effect on any of these parameters. In contrast, the hepatotoxic compound trichloroethylene showed dose-dependent toxicity, as measured by trypan blue (TB) exclusion, LDH leakage, and reduction in GSH content in the present cellular model. These results suggest that praziquantel is a relatively safe drug with respect to liver function.
Transactions of The Royal Society of Tropical Medicine and Hygiene, 1989
Combined low doses of praziquantel and oxamniquine were tested against different stages of Schist... more Combined low doses of praziquantel and oxamniquine were tested against different stages of Schistosoma munsoni in infected Swiss albino mice. The effect of combination therapy (ti the curative dose of praziquantel plus s the curative dose of oxamni-. quine) was compared with the effect of each drug alone, in reduced or full dose. Comparison with infected untreated controls was also made. Drug effects were evaluated on different growth stages of schistosomes by administering the drugs 24 h before infection and b h, 1, 2, 3; 4 and 3 weeks after infection. Animals were killed 8 weeks after infection. Worm burden, distribution, tissue egg load and oogram pattern were used in assessing drug efficacy. A potentiating effect was observed in animals receiving combination therapy. The combination regimen was most effective 4 h after infection, producing 96% worm reduction; eggs were not detected in the liver or intestine. Five weeks after infection the same regimen resulted in 98% reduction in the tissue egg load.
The immunopharmacological properties of praziquantel were studied in mice infected with Schistoso... more The immunopharmacological properties of praziquantel were studied in mice infected with Schistosoma mansoni. Hepatic granuloma measurement was the main parameter of assessment. Delayed foot pad swelling as an in vivo correlate for the delayed granulomatous hypersensitivity reaction was also determined. Fluorescent direct antigen-antibody reaction in the granuloma together with the immediate foot pad swelling were used to test for the humoral immune response. Praziquantel administered at seven weeks after infection in two dose regimens (3 X 250 mg kg-1 for three consecutive days and 3 X 83 mg kg-1 given four hourly within the same day was more or less equally effective in reducing the size of hepatic granuloma by 37-41% two weeks after treatment and by 81-85% one month after treatment. Delayed foot pad swelling using soluble egg antigen (SEA) was significantly suppressed one month after treatment by 53%. At nine weeks after infection the fluorescent antigen-antibody reaction in the granuloma was positive in the untreated controls, but at the same time (i.e. two weeks after treatment) it was negative in the praziquantel-treated mice. One month after treatment positivity was less compared to infected control mice. Reduction in worm burden, hepatic shift of the worms and the reduced number of ova per gram of tissue denoted the efficacy of the drug in its two dose regimens against the Egyptian strain of S. mansoni.
Antimicrobial Agents and Chemotherapy, Jun 1, 2015
Consideration of existing compounds always simplifies and shortens the long and difficult process... more Consideration of existing compounds always simplifies and shortens the long and difficult process of discovering new drugs specifically for diseases of developing countries, an approach that may add to the significant potential cost savings. This study focused on improving the biological characteristics of the already-existing antischistosomal praziquantel (PZQ) by incorporating it into montmorillonite (MMT) clay as a delivery carrier to overcome its known bioavailability drawbacks. The oral bioavailability of a PZQ-MMT clay nanoformulation and its in vivo efficacy against Schistosoma mansoni were investigated. The PZQ-MMT clay nanoformulation provided a preparation with a controlled release rate, a decrease in crystallinity, and an appreciable reduction in particle size. Uninfected and infected mice treated with PZQ-MMT clay showed 3.61-and 1.96-fold and 2.16-and 1.94fold increases, respectively, in area under the concentration-time curve from 0 to 8 h (AUC 0-8) and maximum concentration of drug in serum (C max), with a decrease in elimination rate constant (k el) by 2.84-and 1.35-fold and increases in the absorption rate constant (k a) and half-life (t 1/2e) by 2.11-and 1.51-fold and 2.86-and 1.34-fold, respectively, versus the corresponding conventional PZQ-treated groups. This improved bioavailability has been expressed in higher efficacy of the drug, where the dose necessary to kill 50% of the worms was reduced by >3-fold (PZQ 50% effective dose [ED 50 ] was 20.25 mg/kg of body weight for PZQ-MMT clay compared to 74.07 mg/kg for conventional PZQ), with significant reduction in total tissue egg load and increase in total immature, mature, and dead eggs in most of the drug-treated groups. This formulation showed better bioavailability, enhanced antischistosomal efficacy, and a safer profile despite the longer period of residence in the systemic circulation. Although the conventional drug's toxicity was not examined, animal mortality rates were not different between groups receiving the test PZQ-clay nanoformulation and conventional PZQ.
Context: Calotropis procera (Ait.) R. Br. (Asclepiadaceae), Ficus elastica Roxb. (Moraceae) and Z... more Context: Calotropis procera (Ait.) R. Br. (Asclepiadaceae), Ficus elastica Roxb. (Moraceae) and Zingiber officinale Roscoe (Zingiberaceae) have been traditionally used to treat many diseases. Objective: The antischistosomal activity of these plant extracts was evaluated against Schistosoma mansoni. Materials and methods: Male mice exposed to 80 AE 10 cercariae per mouse were divided into two batches. The first was divided into five groups: (I) infected untreated, while groups from (II-V) were treated orally (500 mg/kg for three consecutive days) by aqueous stem latex and flowers of C. procera, latex of F. elastica and ether extract of Z. officinale, respectively. The second batch was divided into four comparable groups (except Z. officinale-treated group) similarly treated as the first batch in addition to the antacid ranitidine (30 mg/kg) 1 h before extract administration. Safety, worm recovery, tissues egg load and oogram pattern were assessed. Results: Calotropis procera latex and flower extracts are toxic (50-70% mortality) even in a small dose (250 mg/kg) before washing off their toxic rubber. Zingiber officinale extract insignificantly decrease (7.26%) S. mansoni worms. When toxic rubber was washed off and ranitidine was used, C. procera (stem latex and flowers) and F. elastica extracts revealed significant S. mansoni worm reductions by 45.31, 53.7 and 16.71%, respectively. Moreover, C. procera extracts produced significant reductions in tissue egg load ($34-38.5%) and positively affected oogram pattern. Conclusion: The present study may be useful to supplement information with regard to C. procera and F. elastica antischistosomal activity and provide a basis for further experimental trials.
The aggressive use of praziquantel to combat schistosomiasis in Egpyt raises concern about the po... more The aggressive use of praziquantel to combat schistosomiasis in Egpyt raises concern about the possible emergence of resistance. Eggs from Egyptian patients with praziquantel-resistant infections (not cured by 3 doses of praziquantel) have been used to establish infection-specific schistosome isolates in mice. The response of these worms to the drug was observed in vitro, in order to determine if the isolates obtained from these resistant infections were, in fact, less responsive to praziquantel. One of the hallmark effects of praziquantel on schistosomes in vitro is a disruption of the worm's outer surface, the tegument. Here, praziquantel-induced tegumental damage is observed in 3 distinct isolates, 2 derived from resistant infections and 1 from an infection cured by a single dose. The isolates from the resistant infections were less susceptible to praziquantel-induced tegumental damage in vitro, suggesting that the worms are in some way less responsive to the drug.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
International Journal for Parasitology: Drugs and Drug Resistance, 2019
We report the evaluation of 265 compounds from a PDE-focused library for their antischistosomal a... more We report the evaluation of 265 compounds from a PDE-focused library for their antischistosomal activity, assessed in vitro using Schistosoma mansoni. Of the tested compounds, 171 (64%) displayed selective in vitro activity, with 16 causing worm hypermotility/spastic contractions and 41 inducing various degrees of worm killing at 100 μM, with the surviving worms displaying sluggish movement, worm unpairing and complete absence of eggs. The compounds that did not affect worm viability (n = 72) induced a complete cessation of ovipositing. 82% of the compounds had an impact on male worms whereas female worms were barely affected. In vivo evaluation in S. mansoni-infected mice with the in vitro 'hit' NPD-0274 at 20 mg/kg/day orally for 5 days resulted in worm burden reductions of 29% and intestinal tissue egg load reduction of 35% at 10 days posttreatment. Combination of praziquantel (PZQ) at 10 mg/kg/day for 5 days with NPD-0274 or NPD-0298 resulted in significantly higher worm killing than PZQ alone, as well as a reduction in intestinal tissue egg load, disappearance of immature eggs and an increase in the number of dead eggs.
While surveillance cameras are a powerful tool for the prevention, detection and resolving of cri... more While surveillance cameras are a powerful tool for the prevention, detection and resolving of crimes, for most cases the amount of video data has become unmanageable. To ease the analysis, various automatic methods have been proposed, focusing on data-management, detecting suspicious behavior, person recognition, or event reconstruction. In this paper we focus on event reconstruction, in particular on tracing the whereabouts of people. The standard approach for such event reconstruction is to first detect persons in single frames and then match a query to all detections to retrieve the same person in multiple cameras. However, since the number of detected persons is large and performance of matching techniques limited, this process is slow and prone to errors. Intelligent interactive techniques are urged for. We propose to represent detected persons by their complete track within a single camera instead of a single detection and thereby reduce the search-space. On these tracks we use Relevance Feedback to improve recall with only a small effort of the user. Testing the tracking method on a benchmark dataset and a real-life dataset led to a reduction of the search space of 90%, while tracing accuracy based on the distance between tracks improved recall by up to 110% when compared to random tracing. Adding Relevance Feedback led to an additional improvement in recall of up to 400% compared to sequential scanning using the same number of visual assessments.
Background: Schistosomiasis is responsible for a considerable global disease burden. This work ai... more Background: Schistosomiasis is responsible for a considerable global disease burden. This work aimed to improve the therapeutic outcome of the only available antischistosomal drug worldwide, praziquantel (PZQ), by incorporating it into a novel carrier, "solid lipid nanoparticles (SLNs)", to enhance its solubility, bioavailability and efficacy. A simple, cost-effective method was used to prepare SLN-PZQ. Results: Compared to market PZQ (M-PZQ), SLN-PZQ was more bioavailable, as denoted by higher serum concentrations in both normal and infected mice where elevated K a , AUC 0-24 , C max , and t 1/2e with a decrease in k el were demonstrated. The AUC 0-24 for SLN-PZQ in normal and Schistosoma mansoni-infected groups was almost nine-and eight-fold higher, respectively, than that for M-PZQ in corresponding groups. In normal and S. mansoni-infected mice, SLN-PZQ was detectable in serum at 24 h, while M-PZQ completely vanished 8 h post-treatment. Additionally, enhanced absorption with extended residence time was recorded for SLN-PZQ. Compared to M-PZQ, SLN-PZQ revealed superior antischistosomal activity coupled with enhanced bioavailability in all treated groups where higher percentages of worm reduction were recorded with all dosages tested. This effect was especially evident at the lower dose levels. The ED 95 of SLN-PZQ was 5.29-fold lower than that of M-PZQ, with a significantly higher reduction in both the hepatic and intestinal tissue egg loads of all treated groups and almost complete disappearance of immature deposited eggs (clearly evident at the low dose levels). Conclusions: SLN-PZQ demonstrated enhanced PZQ bioavailability and antischistosomal efficacy with a safe profile despite the prolonged residence in the systemic circulation.
Cytophotometric measurement of the effect of praziquantel (500 mg/kg for 2 days) versus hycanthon... more Cytophotometric measurement of the effect of praziquantel (500 mg/kg for 2 days) versus hycanthone (60 mg/kg for 3 days) on hepatocyte nuclear deoxyribonucleic acid (DNA) content was evaluated in Schistosoma mansoni infected mice. Drugs were given 8 weeks post-infection and repeated weekly for 4 weeks. DNA values of infected untreated control and infected drug treated groups were related to the median and upper diploid DNA values of normal control. Schistosoma mansoni infection per se did not change the hepatocyte DNA content, yet aneuploidy was 16. 7%. Praziquantel did not result in significant change of DNA content or ploidy, while hycanthone resulted in marked significant increase of DNA content (328. 9%) and aneuploidy (100%), compared to infected untreated control. Histopathological examination revealed hyperchromatic nuclei with mitosis in the hepatocytes of hycanthone treated mice, but not in praziquantel treated animals. These DNA changes were found to correlate with the reported safety of praziquantel and the carcinogenicity of hycanthone. KEY wokos: hepatocyte DNA, schistosomicidal drugs.
Journal of advanced pharmaceutical technology & research, 2016
Resveratrol is a naturally occurring polyphenol, possesses several pharmacological activities inc... more Resveratrol is a naturally occurring polyphenol, possesses several pharmacological activities including anticancer, antioxidant, antidiabetic, antinociceptive, and antiasthmatic activity. Little is known about its hepatoprotective action mechanisms. This study was conceived to explore the possible protective mechanisms of resveratrol compared with the hepatoprotective silymarin in thioacetamide (TAA)-induced hepatic injury in rats. Thirty-two rats were equally divided into four groups; normal control (i), TAA (100 mg/kg) (ii), TAA + silymarin (50 mg/kg) (iii), and TAA + resveratrol (10 mg/kg) (iv). Liver function and histopathology, pro-inflammatory cytokines, oxidative stress, and apoptotic markers were examined. Data were analyzed using ANOVA test followed by Tukey post hoc test. Compared to TAA-intoxicated group, resveratrol mitigated liver damage, and inflammation as noted by less inflammatory infiltration, hydropic degeneration with decreased levels of tumor necrosis factor-alpha, interleukin-6, and interferon-gamma by 78.83, 18.12, and 64.49%, respectively. Furthermore, it reduced (P < 0.05) alanine and aspartate aminotransferases by 36.64 and 48.09%, respectively, restored hepatic glutathione content and normalized superoxide dismutase and malondialdehyde levels. While it inhibited nuclear factor-kappa B, cytochrome 2E1, and enhanced apoptosis of necrotic hepatocytes via increasing caspase-3 activity. Our findings indicated that the potential hepatoprotective mechanisms of resveratrol are associated with inhibition of inflammation, enhancing the apoptosis of necrotic hepatocytes, and suppression of oxidative stress.
Results from infected patients, not cured by multiple doses of praziquantel (PZQ), have been repo... more Results from infected patients, not cured by multiple doses of praziquantel (PZQ), have been reported from different geographic locations, suggesting that resistance to the drug may be present. This has been coupled with several in vivo (e.g., studies on mice infected with &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;resistant isolates&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;) and in vitro tests (e.g., direct application and measurement of the effects of the drug on schistosomes maintained in culture) demonstrating a significant reduction in the drug&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s efficacy. Despite little field evidence that schistosomes are becoming less sensitive to the drug, 100% cure after PZQ is rarely achieved; meanwhile, the percentage of cure rates in endemic areas could be an overestimate if one accounts for the sensitivity of most egg counting methods coupled with the limited faecal sampling. To be proactive, the efficacy of PZQ has to be monitored on a systematic basis not only for cure, but also for the reduction of egg excretion complemented with periodical assessment for the susceptibility to the drug on local strains. Investigation of field isolates with confirmed diminished sensitivity to the drug will help in determining the frequency, epidemiology, genetic and physiologic basis for the observed resistance. Monitoring for changes in drug responsiveness in high transmission areas, where treatment failure as a result of immature or resistant parasites can not be differentiated, should be initiated. New chemotherapeutic alternatives and strategies in addition to a simple rapid, inexpensive test to detect resistance should be encouraged.
Transactions of The Royal Society of Tropical Medicine and Hygiene, 1986
Schistosoma mansoni egg granulomas were induced in the livers of mice by injecting eggs into sple... more Schistosoma mansoni egg granulomas were induced in the livers of mice by injecting eggs into spleens which had been surgically exposed with their vascular beds intact. Subsequent return of the spleens to a subcutaneous site allows repeated injections of eggs into the liver if necessary.
Murine schistosomiasis is usually associated with hepatic granulomatous lesions together with hig... more Murine schistosomiasis is usually associated with hepatic granulomatous lesions together with high serum and granuloma angiotensin converting enzyme (ACE) activity. Praziquantel (PRZ) which is known to reduce granuloma size was studied to show whether this effect is related to changes in ACE activity. Furthermore, captopril was studied to show whether by inhibiting ACE activity, the drug could also affect granuloma size. PRZ, captopril, and their combination led to significant reduction in liver granuloma. However, in normal mice, captopril was shown to increase rather than decrease serum ACE. The decrease in ACE activity by PRZ was correlated with its curative effect in infected mice. However, in experimentally induced pulmonary granulomata, the drug reduced granuloma size without affecting ACE activity of either serum or granuloma. It may be concluded that reduction in ACE activity may be beneficial as far as diminution of granuloma size is concerned and irrespective of whether there is an active infection or not. The possible use of Captopril as an antihypertensive in bilharzial infections associated with hypertension would probably not adversely affect the granulomatous lesions.
Journal of Traditional and Complementary Medicine, 2019
Few studies reported the antifibrotic effects of gallic acid (GA) despite its known hepatoprotect... more Few studies reported the antifibrotic effects of gallic acid (GA) despite its known hepatoprotective and antioxidant activities. Accordingly, this study investigated the antifibrotic effects of GA through clarifying its mechanisms on hepatic stellate cells' (HSCs) activation, proliferation and/or apoptosis. In vitro effects of GA on HSC-T6 activation/proliferation, morphology and safety on hepatocytes were assessed. In vivo, hepatic fibrosis was induced via chronic thioacetamide (TAA)-intoxication. TAA-intoxicated rats were treated with silyamrin or GA. At end of experiment, liver functions, hepatic MDA, GSH, PDGF-BB, TGF-b1, TIMP-1 and hydroxyproline were determined. Histological analysis and Sirius red staining of hepatic sections, expressions of alpha-smooth muscle actin (a-SMA), proliferating cellular nuclear antigen (PCNA) and caspase-3 were examined. In vitro, GA resulted in a concentration and time-dependent inhibition in HSCs activation, proliferation (IC 50 ¼ 45 and 19 mg/mL at 24 and 48 h respectively); restored the quiescent morphology of some activated HSCs plus its safety on hepatocytes. In vivo, GA reduced ALT, AST, MDA, PDGF-BB levels, collagen deposition and fibrosis score (S1 vs S4); increased caspase-3 expression and restored GSH stores, TGF-b1 level, a-SMA and PCNA expressions. In conclusion, GA counteracted the progression of hepatic fibrosis through reduction of HSCs proliferation/activation mutually with their apoptosis induction.
Context: Hibiscus sabdariffa L. (Malvaceae) is a common traditional tea that has many biological ... more Context: Hibiscus sabdariffa L. (Malvaceae) is a common traditional tea that has many biological activities. Objectives: To evaluate the hepatoprotective effect and study the metabolic profile of the anthocyaninrich extract of H. sabdariffa calyces (HSARE). Materials and methods: The hepatoprotective activity of HSARE was assessed (100 mg/kg/d for 4 weeks) by examining the hepatic, inflammatory, oxidative stress markers and performing a histopathological examination in rats with thioacetamide (TAA)-induced hepatotoxicity. HSARE was analyzed using ultra-performance liquid chromatography-quadrupole-time-of-flight-photodiode array-mass spectrometry (UPLC-qTOF-PDA-MS). Results: The UPLC-qTOF-PDA-MS analysis of HSARE enabled the identification of 25 compounds represented by delphinidin and its derivatives, cyanidin, kaempferol, quercetin, myricetin aglycones and glycosides, together with hibiscus lactone, hibiscus acid and caffeoylquinic acids. Compared to the TAAintoxicated group, HSARE significantly reduced the serum levels of alanine aminotransferase, aspartate aminotransferase and hepatic malondialdehyde by 37.96, 42.74 and 45.31%, respectively. It also decreased hepatic inflammatory markers, including tumour necrosis factor alpha, interleukin-6 and interferon gamma (INF-c), by 85.39, 14.96 and 70.87%, respectively. Moreover, it decreased the immunopositivity of nuclear factor kappa-B and CYP2E1 in liver tissue, with an increase in the effector apoptotic marker (caspase-3 positive cells), restoration of the altered hepatic architecture and increases in the activities of superoxide dismutase (SOD) and glutathione by 150.08 and 89.23%, respectively. Discussion and conclusion: HSARE revealed pronounced antioxidant and anti-inflammatory potential where SOD and INF-c were significantly improved. HSARE possesses the added value of being more water-soluble and of natural origin with fewer side effects expected compared to silymarin.
BMC International Health and Human Rights, Jul 27, 2012
A pool of 38 pan-African Centres of Excellence (CoEs) in health innovation has been selected and ... more A pool of 38 pan-African Centres of Excellence (CoEs) in health innovation has been selected and recognized by the African Network for Drugs and Diagnostics Innovation (ANDI), through a competitive criteria based process. The process identified a number of opportunities and challenges for health R&D and innovation in the continent: i) it provides a direct evidence for the existence of innovation capability that can be leveraged to fill specific gaps in the continent; ii) it revealed a research and financing pattern that is largely fragmented and uncoordinated, and iii) it highlights the most frequent funders of health research in the continent. The CoEs are envisioned as an innovative network of public and private institutions with a critical mass of expertise and resources to support projects and a variety of activities for capacity building and scientific exchange, including hosting fellows, trainees, scientists on sabbaticals and exchange with other African and non-African institutions.
The efficacy of two brands (brand 1 = Biltricide; Bayer AG, Leverkusen, Germany; brand 2 = Distoc... more The efficacy of two brands (brand 1 = Biltricide; Bayer AG, Leverkusen, Germany; brand 2 = Distocide; EPICO pharmaceuticals, Cairo, Egypt) of praziquantel (PZQ) in full and half doses (40 and 20 mg kg-1) monitored as percentage egg reduction and cure rate was investigated in S. mansoni infected school-children. A total of 506 school-children (8-16 years of age) were classified into three groups according to their intensity of infection, heavy [&amp;amp;gt; 500 eggs per grams (epg)], moderate (100-500 epg) and light (&amp;amp;lt; 100 epg), after examination three stool samples (three slides per sample) on three consecutive days. Percentage egg reduction and cure rate were monitored 4 and 10 weeks post-treatment for each dose regimen in the different test groups. Before testing the efficacy of either bran in patients, the pharmacokinetic parameters of the two brands were studied in non-infected normal volunteers. Statistical analysis of the pharmacokinetic parameters of brand 1 vs brand 2 (in a dose of 20 or 40 mg kg-1) revealed no significant difference in elimination (ke), absorption rate constant (ka), elimination half life (t1/2e), area under the time-concentration curve (Auc), serum maximum concentration (Cpmax) and time to maximum concentration (Tmax). As regards the efficacy of test drugs, statistical analysis revealed that up to 10 weeks post-treatment the two brands of PZQ in full dose were equally effective in reducing egg count as their half doses except in heavily infected cases treated with brand 2 of PZQ.(ABSTRACT TRUNCATED AT 250 WORDS)
Treatment with praziquantel (PZQ) has become virtually the sole basis of schistosomiasis control ... more Treatment with praziquantel (PZQ) has become virtually the sole basis of schistosomiasis control in sub-Saharan Africa and elsewhere, and the drug is reviewed here in the context of the increasing rate that it is being used for this purpose. Attention is drawn to our relative lack of knowledge about the mechanisms of action of PZQ at the molecular level, the need for more work to be done on schistosome isolates that have been collected recently from endemic areas rather than those maintained in laboratory conditions for long periods, and our reliance for experimental work mainly on Schistosoma mansoni, little work having been done on S. haematobium. There is no evidence that resistance to PZQ has been induced in African schistosomes as a result of its large-scale use on that continent to date, but there is also no assurance that PZQ and/ or schistosomes are in any way unique and that resistant organisms will not be selected as a result of widespread drug usage. The failure of PZQ to produce complete cures in populations given a routine treatment should therefore solicit considerable concern. With few alternatives to PZQ currently available and/or on the horizon, methods to monitor drug-susceptibility in African schistosomes need to be devised and used to help ensure that this drug remains effective for as long a time as possible.
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