model for southern mediterranean research institute self-assessment: a SWOT analysis-based approach to promote capacity building at theodor bilharz research institute in Cairo [Egypt]

THEBERA is a project funded by the European Union [EU], as an ERA-WIDE FP7 project, aiming to strengthen the Theodor Bilharz Research Institute [TBRI] capacities. A SWOT [strength/weakness/opportunities/threats] analysis of human, structural and organisational existing resources was performed in light of an extensive analysis of liver disease research and clinical management in Egypt, for a full understanding of TBRI needs. Strength and weakness features were identified and analysed, so were actions to be implemented and targets to be accomplished, to develop a business plan gathering the required critical mass [political, scientific, industrial, social] to select investment priorities, to sacrifice non-strategic areas of research, to promote national and international connections and industrial innovations, to update diagnostics and research device technologies and clinical management processes at European levels, to implement fundraising activities, to organise and properly assess training activities for young researchers, physicians, nurses, and technicians. Research institute self assessment is a priority need for sustainable capacity building and for future build-up of a competent health care research institute. Sustainable capacity building strategies must be designed on needs assessment, involving salient requirements: clear strategy, leverage of administrative capacities, industrial support and connections, systematised training programmes and enhancement of mobility of health care staff implemented within ill-defined boundaries and continuously re-evaluated with multiple feedback loops in order to build a complex, adaptable and reliable system based on value

Evaluation of the antibilharzial activity of mirazid versus praziquantel against S. haematobium: an experimental study

Mirazid [myrrh] is a new herbal extract [oleo gum resin from the stem of the plant Commiphora molmol with claimed antibilharzial activity. LD16, LD50, and LD84 of Mirazid were determined in albino mice and were found to be 1984, 3138, and 4963 mg/kg respectively. The antibilharzial efficacy of Mirazid, administered orally at a dose of 250X5 mg/kg, in comparison to the schistosomicidal drug of choice praziquantel [PZQ], administered orally at a dose of 250X2 mg/kg, was evaluated in S. haematobium infected hamsters. Treatment was conducted 90 days post infection. Parasitological parameters expressing cure and hepatic histopathological changes were evaluated 4 weeks after treatment. Praziquantel treatment completely eradicated S.haematobium worms, caused disappearance of immature and mature egg stages, with 100% dead eggs. Hepatic and intestinal tissue egg loads were reduced by 79.2% and 99.7% respectively. Mirazid failed to induce any significant change in total number of worms, but induced significant reduction in the 1[st], 2[nd], and 3[rd] immature egg stages with increase in the number of the fourth stage, but this change was not reflected on the total number of immature eggs. Mirazid did not affect tissue egg load. The hepatic histopathological changes induced by S. haematobium infection were improved in praziquantel treated hamsters with reduction in granuloma number and size. Ova degeneration with regression of granulomatous inflammatory reaction was more manifested when compared to infected untreated controls. Mirazid did not results in evident regression of hepatic schistosomal pathology. In conclusion, praziquantel is still the drug of choice for treatment of S. haematobium, while Mrazid cannot substitute PZQ in the treatment of S. haematobium. Further trials using modified preparations may result in better antibilharzial efficacy of this novel herbal extract preparation

Immunomodulatory effect of splenectomy and its reflection on curative efficacy of praziquantel in experimental schistosomiasis mansoni

The efficacy of praziquantel [PZQ] treatment was assessed in Schistosomiasis mansoni [S. mansoni] infected splenectomized mice by studying worm burden and distribution, tissue egg load and oogram pattern. Moreover, possible immunomodulation as a result of splenectomy and its reflection on the efficacy of PZQ was assessed as well in this model. Immunomodulation was studied by estimation of immunoglobulin G and M levels and measurement of hepatic granuloma size. Two batches of S. mansoni infected Swiss albino mice were splenectomized 6 weeks post-infection and praziquantel was given at a dose of 500 mg/kg/2 days either 2 days or 2 weeks post splenectomy. Animals were sacrificed 2 days, 1, 2 and 4 weeks post treatment. Unsplenectomized praziquantel treated controls corresponding to the splenectomized groups, were included in the study. PZQ was found to be less effective as an antischistosomal drug when given to splenectomized mice. This has been shown by the increase insignificantly in worm burden and significantly in tissue egg load in splenectomized relative to unsplenectomized animals. Diminution in the efficacy of PZQ was accompanied by a decrease in immunoglobulin profile [IgG and IgM] and a reduction in the mean diameter of hepatic granuloma. These findings may point to the importance of the spleen in the elimination of the active S mansoni infection and to its role in maintenance of humoral and cellular host immune responses

Schistosoma mansoni: IgG reactivity to soluble adult worm antigen preparation [swap] in sera of immunized mice with irradiated attenuated and virulent cercariae

The aim of this work was to identify the antigens, that elicit a greater or unique immune response in the immunized host against Schistosoma mansoni [Egyptian strain] infection. Moreover, the difference in immune response to this antigen between mice immunized with radiation-attenuated cercaria or immunized with virulent cercaria were investigated. Immunoblotting technique was used to monitor the fine specificity of host IgG to SDS-PAGE separated SWAP in the sera of different test groups immunized with either radiation-attenuated cercaria or low doses of virulent cercaria compared with non-immunized group

Synthesis and screening of certain aminoguanidine as potential antihypertensive agents

The reaction of 3-ethoxycarbonyl-4,6-dimethyl-2-hydroxypyridine [Ia] with NaOC2H5 afforded the respective sodium salt, which was reacted with certain alkyl halides to give the O-alkyl derivatives [Ib-e]. Hydrazinolysis of Ia-e furnished the corresponding hydrazides [II]. Condensation of the latter with S-methylisothiourea sulfate yielded the target aminoguanidines [III]. Structure of the new compounds was based on microanalytical, IR, HNMR and MS spectral data. Pharmacological screening, indicated that some of the newly synthesized compounds exhibited significant antihypertensive activity in both normal and renal hypertensive rats. Compound IIId produced significant increase in heart rate on normal rats, but compound IIIc and IIIe have no significant effect. Compounds IIIc-e have stimulant action on the isolated rabbit intestine. Antihypertensive and adrenergic neurone blocking activities are reported for many guanidine and aminoguanidine derivatives. Aminoguanidines related to guanethidine from a class of compounds with adrenergic neurone blocking properties. Since nicotinic acid has been reported to exhibit vasodilating and hypotensive effects, it was thought to be of interest to prepare new series of aminoguanidines containing the nicotinoyl moiety for screening as antihypertensive agents

Ocular hypotensive effect of 7 series of newly synthetised adrenoreceptor blockers: 3-[4-[3-[4-aryl-1-piperazinyl]-isopropanoloxy]phenyl]- 4[3H] quinazolones in rabbits

Screening of an ocular hypotensive effect of seven newly synthesized B-blockers was performed. Aqueous solutions of the hydrochloride salts of the drugs, given the code 3a, b, c, d, f, g were applied locally [50 ug/0.25 ml] or administered intravenously through the marginal vein [1 mg/kg] in groups of adult healthy male rabbits, each of 6 animals. Controls used were saline solutions having the same pH as that of the drugs. The intraocular pressure [IOP] was measured using weighted Schiotz tonometer at different time intervals ranging from 15-405 minutes after the drug administration, and compared with controls. The intravenous administration of all drugs tested induced hypotensive action. The onset of action appeared after 45, 60, 45, 30, 75, 15 and 75 minutes, while the duration of action lasted for 150, 310, 210, 120, 90, 60 and 105 minutes respectively. The peak of ocular hypotensive effect of these drugs were obtained after 75, 150, 105, 45, 75, 30 and 75 minutes and amounted to 24.9%, 37.4%, 40.6%, 24.5%, 24.5%, 24.6% and 20.7% respectively. On the other hand, the topical application of drugs, 3 a, b, c, d, e, g, induced an ocular hypotensive action. Its onset appeared after 75, 60, 75, 120, 90 and 75 minutes. While, their duration of action was 165, 300, 270, 135, 240 and 165 minutes respectively. Time peak of ocular hypotensive effect of these drugs were obtained after 120, 240, 180, 120, 150 and 120 minutes respectively and amounted to 42,7, 33.9, 38.6, 25, 27.9 and 21.2% respectively. Screening of these drugs point to a probable useful ocular hypotensive agents which needs further clinical studies

Hepatocyte nuclear deoxyribonucleic acid changes after repeated administration of oxamniquine and amoscanate in experimental schistosomiasis mansoni

Hepatocyte deosoxiribonucleic acid [DNA] content of Schistosoma mansoni [S. Mansoni] infected, oxamniquine treated and infected amoscanate treated mice, were compared to the median 2C "diploid" value and the upper diploid limit [P 90] of a reference control of normal mice hepatocytes. Each of the test drugs was given in a dose of 100 mg/kg for 5 days. Drug doses were repeated weekly for 4 weeks. S. mansoni infection alone did not result in a significant change in the hepatocyte DNA content and the frequency distribution histogram was diploid as normal mice, apart from some scattering of DNA values a 16.7% aneuploidy. Both oxamniquine and amoscanate increased the hepatocyte DNA content significantly by 51.9 and 136.9% respectively.% aneuploidy was 83.3% for the former and 100% for the latter drug. DNA frequency distribution histogram was "triploid" in oxamniquine treated animals and "aneuploid" with erratic scattering of DNA values in amosoanate treated mice. Histopathological examination showed hyperchromatic nuclei and mitosis with both drugs. Moreover, a microscopic area of altered hepatocytes cellularity with identified mitosis was found in the liver of one of the oxamniquine treated animals

Synthesis of novel 1,4-disubstituted piperazines as potential antihypertensive agents

Two series of 1-arylpiperazines linked to nicotinic acid moiety were prepared as potential antihypertensive agents. The first series [compounds II] was prepared via the Mannich reaction of N-nicotinoyl with 4-amino-benzoic acid to give N-nicotinoyl-4-aminobenzoic acid. The latter was treated with thionyl chloride to give the corresponding acid chloride which was reacted with 1-arylpiperazines to give IV. Preliminary screening of the synthesized compounds was performed for their antihypertensive activity

Study of some immunomodulatory properties of the new immunoregulant adamantylamide dipeptide in schistosoma mansoni infected mice treated with praziquantel

The effect of the new immunoregulant adamantylamide dipeptide [AdDP] was studied in Schistosoma mansoni [S. mansoni] infected mice treated with praziquantel [PZ], using three parameters, worm and tissue egg loads, hepatic granuloma volume and percent lymphocytes forming EAC-rosettes, Three groups of mice were infected with S. mansoni cercariae: the first served as infected untreated control; the second received oral PZ [2 X 500 mg/kg] 45 days post infection; the third was given PZ as in the second group and 2 weeks later AdDP was administered [2 X 0.5 mg/mouse] intraperitoneally. Animals were sacrificed one week after AdDP therapy or day equivalent for the other groups. Significant reduction in hepatic granuloma volume was recorded after PZ alone [45.76%] versus 17.96% when AdDP was given after PZ, compared to infected untreated control. No signifcant change was recorded in the percent lymphocytes forming EAC-rosettes, or in the worm and tissue egg loads, between mice receiving PZ alone and those treated with PZ and AdDP, compared to infected untreated control. Findings revealed that AdDP could counteract PZ-induccd immunodepression of granuloma volume, but could neither enhance a non suppressed immunologic reaction [EAC-rosettes] nor help ridding the animal from an established infection after PZ therapy

Syntheses and biological evaluation of zwitterionie opioid agonists

A series of zwitterionic B-oxymorphine derivatives were synthesized that contain a variety of acyl groups with terminal carboxyl group attached at the 6=NH2 group of B-oxymorphine [1a]. Compounds 1b-d were synthesized by reacting with the appropriate acid anhydride. The aspartic acid derivative le was prepared by reacting la with Bocaspartic acid monobenzyl ester using DCC and HOBt, followed by deprotection with HCI and hydrogenation over Pd/C. The fumaric acid derivative if was synthesized by reacting la with fumaric acid monoethyl ester using DCC and HOBt followed by hydrolysis with NaOH. Reacting oxymorphine [2a] with carboxy-methoxyl-amine gave 2b. Two of the synthesized compounds 1c and 1d were found to be potent reversible agonists as tested in the GPI preparation

Effect of specific chemotherapy on serum enzymes in patients with schistosomiasis

The morbidity of sehistosomia sis reflected on the electrophoretic and enzymatic liver functions was studied in patients with either S. mansoni or mixed infection. The reflection of specific chemotherapy [praziquantel] on the morbidity of the disease was studied 48 hours, one, two, and four weeks after treatment. S. mansoni infection produced a significant decrease in the albumin level with corresponding increase in the gamma-globulin fraction, alkaline phosphatase and transaminases. In mixed infection the pattern of changes was nearly that of single S. mansoni infection apart from a significant increase in the bilirubin level. Praziquantel normalized albumin globulin changes in patients with mixed infection, no statistically significant changes were recorded throughout the period of observation

Effect of combined low dose praziquantel and oxamniquine on different stages of schistosome maturity

The effect of combined low dose praziquantel and oxamniquine on different stages of schistosome maturity was studied in Schistosoma mansoni infected Swiss albino mice. The effect of combination therapy [1/3 the curative dose of praziquantel + 1/3 the curative dose of oxamniquine] was compared with the effect of each drug solely whether in reduced dose or in full dose. Comparison with infected untreated controls was also done. Test drug effects were evaluated on different stages of schistosome maturity by administering these drugs 24 hours before infection, four hours one, two, three, four and five weeks after infection. Animals were sacrificed eight weeks post-infection. Worm burden, distribution,tissueeggloadand oogram pattern were the parasitological criteria used in assessing drugefficacy. A synergistic activity was recorded on different stages of schistosome maturity in animals receiving combination therapy. Combination regimen was maximally effective four hours after infection [95.89% parasite reduction]. In addition, tissue egg load was very low in animals treated five weeks after infection and eggs were not detected in the tissues of infected mice treated four hours post-infection

Synthesis of pyrido [2,3-d] pyrimidines from 2-amino-3cyanopyridines

The preparation of a number of 1-arylpyrido [2,3-d] pyrimidine-2,4-[lH,3H]-diones is described. Treatment of 2-chloro-3-cyanopyridine with primary aromatic amines afforded the corresponding 2-arylamino derivatives which were hydrolyzed with 40 percent H2SO4 to 2-arylamino-3-pyridinecarboxylic acids. The reaction of the latter compounds with urea yielded the desired pyrido [2, 3-d] pyrimidines. 2-anilino-3-cyanopyridine [II] was allowed to react with urea at 250 degree to give 4-imino-l-phenylpyrido [2, 3-d] pyrimidin-2-[1H, 3H]-one as shown by ir, nmr and mass spectra. Reacting II with ethyl chloroformate yielded the corresponding N-ethoxycarbonyl derivative which upon reaction with hydrazine, it was deacetylated and reverted back to II

Synthesis of pyrazolo [3,4-b] pyridine derivatives

The reaction of 3-amino-5-pyrazolones with 1, 3-dicarbonyl compounds has been shown to give either pyrazolo[l,5-a] pyrimidine or pyrazolo [3,4-b] pyridines depending on the conditions employed. The pyrazolo [3,4-b] pyridines were reported to be valuable from both the pharmacological and antimicrobial view points. Consequently, the present work comprised the investigation of the reaction of l-phenyl-3-amino-5-pyrazolone [I] with ethyl acetylpyruvate [II] aiming to synthesise pyrazolo [3,4-b] pyridine derivatives of biological interest

Synthesis of amidrazones from 2-ethoxycarbonyl-4H-3,1benzoxazin-4-one

In aprevious publication [1], the authors gave a report of the reaction of 2-lethoxycarbonyl-4H-3,l-benzoxazin-4-one [I] with certain amino compounds. In continuation, we decided to study the behaviour of [1] with hydrazine and its derivatives. Bogert [2] reported that direct interaction of [I] with hydrazine and phenylhydrazine yielded 3-amino-4[3H]-quinazolone derivatives. In the present investigation, the reaction of [I] with phenylhydrazine and carboxyl-ic acid hydrazides in dioxane or ethanol yielded compounds of the general formula [III], which were shown to be oxalmonoamidrazone derivatives