Study of ochratoxin A as an environmental risk that causes renal injury in breast-fed Egyptian infants

Ochratoxin A (OTA) constitutes a real human threat. Its presence in human milk has previously been reported in different countries. This study is the first Egyptian report on the presence of OTA in both mothers milk and infants sera, addressing its correlation with infants kidney functions, which was not previously addressed in the literature. Fifty healthy breast-lactating mothers and their infants who were exclusively breast-fed for at least 4 months were included. All of them were subjected to a thorough laboratory evaluation including determination of OTA concentration by high-performance liquid chromatography. Thirty-six mothers (72%) and their infants had been contaminated with OTA. Univariate analysis showed that the presence of OTA was associated with significantly higher levels of urinary 2 microglobulin and microalbuminuria. Multivariate logistic regression analysis showed that there was a significant correlation between a higher OTA level in infants sera and the degree of microalbuminuria. Mothers and their infants in our locality are exposed to a high OTA contamination rate (72%). To establish the role of OTA in causation of future renal dysfunction for infants, large controlled studies are warranted.     

Synthesis of 1-acyl-2-alkylthio-1,2,4-triazolobenzimidazoles with antifungal, anti-inflammatory and analgesic effects

Some new derivatives of 1,2,4-triazolo[2,3-a]benzimidazoles were synthesized through the reaction of 1,2-diaminobenzimidazole with carbon disulfide. The resulting 1,2,4-triazolo[2,3-a]benzimidazole-2-thione intermediate reacted with one equivalent of the alkyl halide to give the corresponding 2-alkylthio derivative 3a-g. The latters were acylated to afford the 1-acyl-2-alkylthio-1,2,4-triazolo[2,3-a]-benzimidazole derivatives 4-10 in good yields. Structures of the new compounds were verified on the basis of spectral and elemental methods of analyses. Fourteen of the prepared compounds were tested for their possible antifungal activities. Most of the tested compounds showed activity against Candida albicans and Fusarium oxysporum comparable to that of fluconazole as a reference drug. Compounds 8a, 9a, and 10d are the most active ones against most of the fungi used. Compounds 3e, 4d, 5d, 6d, 7d, 8c, 8d, 9d, and 10d were tested for their anti-inflammatory and analgesic effects; most of these compounds showed potent and significant results compared to indomethacin. Moreover, ulcerogenicity and the median lethal dose (LD(50)) of the most active compound 8d were determined in mice; LD(50) was found to be 275 mg kg(-1) (i.p.).     

Synthesis of beta-hydroxypropanoic acid derivatives as potential anti-inflammatory, analgesic and antimicrobial agents

A series of new 3-(substituted) 3-hydroxy-propanoic acid ethyl esters 1a-c, hydrazides 2a-c, thiosemicarbazides 3a-f, and semicarbazides 3g, 3h has been synthesized. Cyclization of compounds 3a-d in basic medium yielded 1,2,4-triazole-5-thiones 4a-d. On the other hand, reaction of hydrazides 2a-c with CS(2 )in basic medium afforded 1,3,4-oxadiazole-5-thiones 5a-c. All the synthesized compounds were characterized by their physical and spectral analyses data. The newly synthesized compounds were evaluated for their anti-inflammatory, analgesic, and antimicrobial activities. Compounds 1c, 3g, 4a, 4b, 4c, and 5c exhibited comparable anti-inflammatory activity to that of indomethacin and compounds 1c, 4c, and 5c were more analgesics than acetyl salicylic acid. Compounds 4b, 4c, and 5c showed superior GI safety profile (33.3%, 33.3% and 50.0% ulceration) than that of indomethacin (100% ulceration) at 100 mg/kg oral dose. Compounds 4b, 4c, and 5c were also non-toxic with a median lethal dose (LD(50)) up to 200 mg/kg. The antibacterial and antifungal screenings identified compounds 3c, 4b, 4d, 5a, and 5b as the most effective against a variety of tested microorganisms.     

Growth stimulation of human pulmonary adenocarcinoma cells and small airway epithelial cells by beta-carotene via activation of cAMP, PKA, CREB and ERK1/2

An alpha-tocopherol, beta-carotene supplementation trial (ATBC) and a chemoprevention trial with beta-carotene and retinoids (CARET trial) were conducted in the 1990s in populations at risk for the development of lung cancer. Both trials had to be discontinued due to significant increases in lung cancer and cardiovascular mortality. Clinical trials to test the cancer preventive effects of beta-carotene are still ongoing, and high concentrations of this provitamin are contained in numerous dietary supplements. Using a cell line derived from a human pulmonary adenocarcinoma (PAC) of Clara cell lineage and immortalized human small airway epithelial cells, our data show that low concentrations of beta-carotene that can be realistically expected in human tissues after oral administration caused a significant increase in intracellular cAMP and activated PKA, as well as in phosphorylation of ERK1/2 and CREB. Furthermore, the proliferation of cells was significantly stimulated by identical concentrations of beta-carotene as monitored by MTT assays. Control experiments with retinol also showed stimulation of cell proliferation and activation of PKA in both cell lines. In light of the fact that PAC is the leading type of lung cancer, these findings suggest that the growth promoting effects of beta-carotene on this cancer type observed in our experiments may have contributed to the unfortunate outcome of the ATBC and CARET trials. This interpretation is supported by the fact that elevated levels of cAMP in the cardiovascular system play a major role in the genesis of cardiovascular disease, which was also greatly promoted in the CARET trial. Our data challenge the widely accepted view that beta-carotene may be useful as a cancer preventive agent.     

Plasma cobalamin and folate and their metabolic markers methylmalonic acid and total homocysteine among Egyptian children before and after nutritional supplementation with the probiotic bacteria Lactobacillus acidophilus in yoghurt matrix

OBJECTIVE: To evaluate the biopotency of the viable probiotic Lactobacillus acidophilus (La1) in yoghurt matrix consumed by Egyptian children on their plasma vitamin B12 and folate levels, and their metabolic markers methylmalonic acid (MMA) and total homocysteine (t-Hcy). METHODS: A randomized nutritional supplementation trial (42 days duration) was performed in free-living children of both sexes (11 years old). The La1 in yoghurt matrix was administered to provide 1012 colony-forming units/subject/day. Blood sampling for the analysis of plasma vitamin B12, folate and t-Hcy was performed by standardized methods. Five-hour urine collection was used for the analysis of MMA and t-Hcy. RESULTS: Initially 33.3% of the children presented with biochemical vitamin B12 deficiency (<208 pg/ml), while one-fifth (21%) were biochemically deficient in folate (<3 ng/ml folate/ml plasma or 0.68 nmol/l). Fifty percent of the children presented with high plasma t-Hcy (>15.0 micromol/l). The daily consumption of the probiotic La1 yoghurt for 42 days significantly improved the mean levels of plasma vitamin B12 (P<0.05) and folate (P<0.01) among the studied children compared with the respective baseline data. On the other hand, the average levels of plasma t-Hcy and urinary MMA decreased significantly (P<0.05) at the termination of the 42-day nutritional supplementation, compared with the respective initial mean levels. The consumption of the probiotic yoghurt was also associated with a significant (chi2=8.0; P<0.01) reduction in the percentage prevalence of anemia (hemoglobin <120 g/l). CONCLUSION: The long-term ingestion of viable probiotic La1 potentially promoted the overall nutritional status of the studied children.     

Phase I trial of continuous infusion recombinant human interleukin-4 in patients with cancer

BACKGROUND: A phase I study using recombinant human interleukin-4 (rhuIL-4) administered as a continuous intravenous infusion was conducted in patients with advanced cancer to study the toxicity profile and to determine the maximum tolerated dose (MTD) of this cytokine. METHODS: Twenty-six patients with non-hematologic malignancies were treated with escalating doses of rhuIL-4 administered as 24-hour continuous intravenous infusion on days 1-5 and 15-19 every 28 days. The dose levels of rhuIL-4 were: dose level I-0.25 microg/kg/day (3 patients), dose level II-0.5 microg/kg/day (5 patients), dose level III-1.0 microg/kg/day (3 patients), dose level IV-2.0 microg/kg/day (10 patients) and dose level V-4.0 microg/kg/day (5 patients). RESULTS: Dose limiting toxicity of continuous infusion rhuIL-4 occurred at 4.0 microg/kg/day D1-5 and 15-19, in three of five patients and consisted of hematologic (thrombocytopenia and prolongation of PT) and neurologic (headache and neurocortical toxicity) toxicity. A mild flu-like syndrome characterized by fever, chills, fatigue, headache, anorexia, arthralgias and myalgias was seen almost universally, occurred more commonly and with increasing severity with higher dose levels and resolved completely on discontinuing therapy with rhuIL-4. None of the enrolled patients had an objective response to treatment with continuous infusion rhuIL-4. CONCLUSIONS: A five-day continuous infusion of rhuIL-4 given biweekly is well tolerated with a MTD of 2.0 microg/kg/day.     

Quality of age data in patients from developing countries

BACKGROUND: Age misreporting is common in demographic studies but the prevalence and magnitude of age misreporting in clinical cohorts is unknown. We analysed single-year age distribution and terminal digit preference in cancer patients from developing countries. METHOD: Age distribution was analysed by plotting a single-year age of 3874 cancer patients from 72 different countries, mainly from the Indian subcontinent and the Middle East, who resided in the UAE at the time of cancer diagnosis. Preference for age ending with digits '0' and '5' was evaluated using Whipple's index (WI), which has value 100 in cohorts without preference. Preference for all 10 terminal digits was expressed as the difference between the found and expected frequencies using Myers blended method and was graphed. RESULTS: Age data quality was low in cancer patients from the Indian subcontinent (WI = 177) and Middle Eastern countries (WI = 113-204). Females of all nationalities supplied better quality of age data (lower WI) than males. Preference for age ending with digits '0' and '5' was found in all populations except the UAE male citizens who did not show preference for terminal digit '0'. CONCLUSION: Age data quality in this cohort of patients from developing countries was low. Preference for age ending with numbers '0' and '5' is common. In studies conducted in developing countries, age data quality should be analysed as it may bias results and weaken the power of the study.     

Photorefractive keratectomy for pediatric anisometropia: safety and impact on refractive error, visual acuity, and stereopsis

PURPOSE: To establish the safety and possible efficacy of excimer laser photorefractive keratectomy (PRK) for treatment of pediatric anisometropia. DESIGN: Interventional case series METHODS: This is a prospective, noncomparative interventional case series at an individual university practice of photorefractive keratectomy in 11 children aged 2 and 11 years with anisometropic amblyopia who were unable or unwilling to use contact lens, glasses, and occlusion therapy to treat the amblyopia. The eye with the higher refractive error was treated with PRK using a standard adult nomogram. The refractive treatment goal was to decrease the anisometropia to 3 diopters or less. Main outcome measures were cycloplegic refraction, refractive correction, degree of corneal haze, uncorrected and best spectacle-corrected visual acuity, and stereopsis over 12 months. RESULTS: All patients tolerated the procedure well. The mean refractive target reduction was -10.10 +/- 1.39 diopters for myopia and +4.75 +/- 0.50 diopters for hyperopia. The mean achieved refractive error reduction at 12 months for myopia was -10.56 +/- 3.00 diopters and for hyperopia was +4.08 +/- 0.8 diopters. Corneal haze at 12 months was minimal. Uncorrected visual acuity improved by 2 or more lines in 6 (75%) of the eight children able to perform psychophysical acuity tests. Best spectacle-corrected visual acuity improved by 2 lines in 3 (38%) of patients. Stereopsis improved in 3 (33%) of nine patients. CONCLUSIONS: Pediatric PRK can be safely performed for anisometropia. The refractive error response in children appears to be similar to that of adults with comparable refractive errors. Visual acuity and stereopsis improved despite several children being outside the standard age of visual plasticity. Photorefractive keratectomy may play a role in the management of anisometropia in selected pediatric patients.     

Phenolic sodium sulphates of Frankenia laevis L

Four new phenolic anionic conjugates have been isolated from the whole plant aqueous alcohol extract of Frankenia laevis L. Their structures were established, mainly on the basis of ESI-MS, 1D and 2D NMR spectroscopic evidence, as gallic acid-3-methyl ether-5-sodium sulphate, acetophenone-4-methyl ether-2-sodium sulphate, ellagic acid-3,3'-dimethyl ether-4,4'-di-sodium sulphate and ellagic acid-3-methyl ether-4-sodium sulphate.