Effect of an Extract from the Egyptian Sea Cucumber,Bohadschia marmorata,on Methotrexate-Induced Hepatorenal Toxicity in Male Mice

Background: The sea cucumber, Bohadschia marmorata, is a marine echinoderm consumed and used as a medication. Extract of this species displays a broad spectrum of bioactivity, such as antifungal, antibacterial, immunomodulatory, and cytotoxic properties. This investigation explored sea cucumber extract for hepatorenal protection against the toxicity of methotrexate (MTX). Methods: Four groups of mice were divided into G1: control, G2: MTX treated, G3: B. marmorata extract-treated daily for 14 days, and G4: B. marmorata extract and MTX treated. Results and Conclusions: Biochemical analysis and histopathological examination of liver tissue showed that administration of MTX increased serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), lowered levels of serum albumin, total protein, Superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). Administration of B. marmorata extract to MTX- injected mice significantly reversed the increase in serum levels of liver enzymes and induced a significant elevation in serum albumin and total protein levels. SOD, CAT, and GSH levels returned to nearly normal levels. Histopathological examination indicated fewer signs of toxicity in liver and kidney tissues of mice treated with both extract and MTX compared to MTX treatment alone. An extract of B. marmorata will protect mice from hepatorenal toxicity induced by MTX.     

Exposure of chromatin and not high affinity for dsDNA determines the nephritogenic impact of anti-dsDNA antibodies in (NZB×NZW)F1 mice

Recent studies have demonstrated that the nephritogenicity of antibodies to dsDNA and nucleosomes confers to binding of glomerular membrane-associated nucleosomes, and not to cross-reacting glomerular antigens. There is no known parameter that determines antibody pathogenicity aside from specificity for dsDNA/nucleosomes, and systemic lupus erytheomatosus (SLE) patients may have high titer anti-dsDNA antibodies irrespective whether they have lupus nephritis or not. One parameter may be antibody affinity, as theoretically only high affinity antibodies may bind in vivo in a stable way. This was analyzed in (NZB × NZW)F1 mice with full-blown lupus nephritis. These mice had serum antibodies to dsDNA, and IgG autoantibodies bound in situ in glomerular membrane-associated electron dense structures as determined by immune electron microscopy (IEM). Intrinsic affinity of purified circulating and glomerular IgG anti-dsDNA antibodies was determined by surface plasmon resonance. The results demonstrate that affinity of glomerular-bound anti-dsDNA antibodies was higher than for those in circulation. However, affinity of glomerular in situ-bound antibodies from different mice varied considerably, from K_D in the range from 10^{? 8} to 10^{? 13}. These results indicate that antibody affinity is not a decisive pathogenic factor, but rather that availability of chromatin fragments may be the factor that determines whether an anti-dsDNA antibody binds in glomeruli or not.     

Ocular administration of acetazolamide microsponges in situ gel formulations

In the present work, the antiglaucoma drug, acetazolamide, was formulated as microsponges in situ gel for ocular drug delivery aiming an improved therapeutic efficacy and reduction in the systemic side effects of oral acetazolamide. The microsponges were prepared by the quasi emulsion solvent diffusion method and were incorporated into 25% pluronic F-127 in situ gel. Ethyl cellulose polymer in different proportions with drug was used to prepare the microsponges. Different parameters were evaluated to select the best formulation. The formula S2 with drug to polymer ratio (2:1) showed high entrapment efficiency of about 82% and mean particle size of about 10?µm with polydispersity index (PDI) of 0.22, which are suitable characters for ocular delivery. The in situ gels were evaluated for physicochemical properties (pH, gelling capacity, gelation time and rheological properties) and in vivo studies. S2 formulation showed higher therapeutic efficacy compared to free drug in gel. It was non irritant to the rabbit's eye. These results indicated that acetazolamide microsponges in situ gel have potential ability for ophthalmic delivery.     

In vitro antifungal susceptibility testing of fungi in patients with onychomycosis

Onychomycosis is the most common nail disorder. To examine in vitro antifungal susceptibility of fungi among onychomycosis patients. The study included 68 patients with onychomycosis. Nail specimens were cultured on Sabouraud dextrose agar and Dermasel agar base‐media. Isolated fungi were subjected to antifungal susceptibility tests against terbinafine, itraconazole, fluconazole, and griseofulvin. Candida species (Candida spp.) were detected in 32.4% of the cases of candidal onychomycosis (n = 37), 23.5% of the cases of distal and lateral subungual onychomycosis (n = 17), and 21.4% of the cases of total dystrophic onychomycosis (n = 14). Candida spp. were sensitive to fluconazole in 73.5%, itraconazole in 58.8%, and terbinafine in 5.9% of the cases. Aspergillus spp. were sensitive to itraconazole in all cases, and terbinafine in 87.5% of cases. Penicillium spp. were sensitive to itraconazole and terbinafine in 88.9% and 77.8% of cases, respectively. Trichophyton spp. were sensitive to terbinafine and resistant to itraconazole. Microsporum spp. were sensitive to itraconazole and resistance to terbinafine. All isolated fungi were resistant to griseofulvin. An increasing proportion of Candida spp. was observed among patients with different clinical varieties of onychomycosis. Candida spp. were highly sensitive to fluconazole and a lesser extent to itraconazole.     

Thiosemicarbazide functionalized carbon quantum dots as a fluorescent probe for the determination of some oxicams: application to dosage forms and biological fluids

In this study, highly fluorescent water-soluble nitrogen and sulfur doped carbon quantum dots (N, S-CQDs) were synthesized via a one-step hydrothermal process utilizing citric acid as a carbon source and thiosemicarbazide as a sulfur and nitrogen source. The obtained N, S-CQDs exhibited an intense emission band at 415 nm (λ_ex = 345 nm). In the presence of either piroxicam, tenoxicam or lornoxicam, the emission band at 415 nm was significantly quenched which might be triggered due to destruction of the surface passivation layer of the N, S-CQDs. A linear correlation was found between the reduction in the fluorescence intensity of N, S-CQDs and the concentration of each drug in the ranges of 2.0–25.0 μM, 10.0–100.0 μM and 20.0–200.0 μM with correlation coefficients of more than 0.999 for all drugs. The detection limits were 0.49 μM, 1.58 μM and 4.63 μM for piroxicam, tenoxicam and lornoxicam, respectively. The effect of experimental parameters affecting the performance of the method was investigated and optimized. The developed sensor has the advantages of simplicity, time-saving, convenience and satisfactory selectivity for determination of the studied drugs in dosage forms with high % recoveries (98.86–101.69%). The method was extended for determination of piroxicam in spiked plasma with % recoveries ranging from 97.95–101.36%. The method was validated in accordance with International Council of Harmonization (ICH) standards, and the results obtained were compared statistically to those given by reported methods, indicating no significant differences in the level of accuracy and precision. The mechanism of the quenching process was studied and elucidated. The structure–activity relationship between the three drugs and the quenching efficiency was also studied and discussed.

Highly fluorescent nitrogen and sulfur doped carbon quantum dots were synthesized via hydrothermal process using citric acid and thiosemicarbazide. The dots had an emission band at 415 nm (λ_ex = 345 nm). The polarity of the studied drugs affects the method’s sensitivity.     

Spongiform encephalopathy in siblings with no evidence of protease-resistant prion protein or a mutation in the prion protein gene

We discuss relevant aspects in two siblings with a neurodegenerative process of unclear aetiology who developed progressive dementia with global aphasia and hyperoral behaviour at the ages of 39 and 46 years and who died 6 and 5 years after disease onset. The cases were reported to the National Reference Center for TSE Surveillance in Göttingen, Germany. Detailed clinical examinations, CSF, blood samples, and copies of the important diagnostic tests (magnetic resonance imaging, electroencephalogram, laboratory tests) were obtained. Further neuropathological and genetic analyses were performed. Cerebral magnetic resonance imaging of both siblings showed prominent changes in signal intensity, especially in the left medial temporal cortex, but also the hippocampal formation. Neuropathological examination revealed spongiform changes, neuronal loss, and astrocytic gliosis, which are typical in Creutzfeldt–Jakob disease. However, no prion protein deposits were detectable by immunohistochemical analysis, Western blot, or PET blot, though abundant tau protein deposits were observed. A mutation in the coding region of the prion protein genes of both siblings was excluded. A detailed search of the literature revealed no other cases with a similar clinical and neuropathological appearance. While the disease aetiology remains unclear, the findings point to a neurodegenerative process and most likely a genetic disease.     

Seroprevalence of and risk factors for Toxoplasma gondii antibodies among asymptomatic blood donors in Egypt

A cross-sectional study was conducted to evaluate the seroprevalence of and risk factors for Toxoplasma gondii antibodies in 260 blood donors seen at blood banks in Mansoura University Hospital, Egypt. Blood donors were interviewed about sociodemographic characteristics and risk factors for T. gondii infection. A blood sample was taken to document their T. gondii antibody status using enzyme-linked immunosorbent assay. Overall, 155 (59.6%) of 260 blood donors were positive for anti-T. gondii IgG antibodies. Multivariate logistic regression analysis showed a significant association between T. gondii seropositivity and eating meat by-products (luncheon/shawerma) (adjusted odds ratio [OR] 80.82 [95% CI 18.62–350.81], P < 0.0001) or being non-educated (adjusted OR 32.25 [95% CI 7.46–139.44], P < 0.0001). These findings highlight that T. gondii is prevalent among blood donors in Egypt.