Development of a new stability indicating method for the simultaneous separation of voriconazole from its impurities along with sodium benzoate used as a preservative in a powder for oral suspension.

Voriconazole is a second-generation triazole derived from fluconazole, having an enhanced antifungal spectrum, compared with older triazoles. It is the drug of choice for treatment of invasive aspergillosis and many Scedosporium/Pseudallescheria Fusarium infections. Voriconazole is available in both intravenous and oral formulations. Since there is much interest in pharmaceutical quality control, separation of impurities from the main drug substances and accurate assay quantification, and since there is no reference or monograph until nowadays reported for the simultaneous separation of voriconazole from its specified and unspecified impurities along with sodium benzoate used as an antimicrobial preservative, our aim of this work is to develop a new simple, sensitive and stability indicating assay method allowing thus separation by high-performance liquid chromatography. The development of our method consisted in optimizing the following analytical parameters: nature and composition of the mobile phase, its pH, buffer concentration, nature of the stationary phase, column temperature and detection wavelength. After optimisation, separation was achieved on a stainless steel column NOVAPACK C18 (3.9mm×150mm; 4µm particle size) using a gradient mode with methanol, acetonitrile R and an aqueous solution acidified by acetic acid at 1% and adjusted to pH 2.77. The eluted compounds were monitored at 254nm. The flow rate was set at 1.0mL/min, the injection volume at 10µL, and the column oven temperature was maintained at 35°C. Under these conditions, separation was achieved with good resolution and symmetrical peaks' shape. The developed method was validated according to the International Conference on Harmonization (ICH) guidelines, and then it was successfully applied to establish inherent stability of the pharmaceutical formulation subjected to different ICH prescribed stress conditions. The developed method was proved to be simple, specific and precise. Hence, it can be considered as a method for stability study and for routine quality control analysis of voriconazole and sodium benzoate in a powder for oral suspension.

Potential Hepatoprotective Effect of Cheatomorpha gracilis extract against High Fat Diet (HFD)-Induced Liver Damage, and its characterization by HPLC.

The current investigation was carried out to estimate the protective effect of aqueous extract of Cheatomorpha gracilis (AEC) against High fat Diet (HFD) induced liver damage in mice. The results of the in vitro study showed that AEC have higher antioxidant capacities in the DPPH and hydroxyl radical-scavenging assays. Indeed, many phenolic compounds (gallic acid, quercetin, naringenin, apigenin, kaempferol and rutin) were identified in the AEC. In the animal studies, during 6 weeks, HFD promoted oxidative stress with a rise level of malonaldehyde (MDA), protein carbonyls (PCOs) levels and a significant decrease of the antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase. Interestingly, the treatment with AEC (250 mg/kg body weight) significantly reduced the effects of HFD disorders on some plasmatic liver biomarkers (AST, ALT and ALP) in addition to, plasmatic proteins inflammatory biomarkers (α2 and ß1 decreases / ß2 and γ globulins increases). It can be suggest that supplementation of MECG displays high potential to quench free radicals and attenuates high fat diet promoted liver oxidative stress and related disturbances.

Diagnosis and management of autoimmune hemolytic anemia in children.

BACKGROUND AND AIM: The aim of this study is to evaluate the clinical, biological and hematological profiles of autoimmune hemolytic anemia (AIHA) in children and to specify its etiologies, therapeutic modalities, and treatment responses. METHODS: This is a 14-year retrospective study of AIHA cases collected at the department of pediatric emergency and reanimation of Hedi Chaker University Hospital in Sfax. We included patients under 14 years old with clinical and biological features of hemolysis and a positive direct antiglobulin test (DAT). The selected patients' demographic characteristics, physical signs, laboratory findings, and treatment responses were recorded. RESULTS: Thirteen cases of AIHA were collected, including 8 girls and 5 boys. The median age at diagnosis was 4 years and 6 months (range: 8 months to 13 years). Consanguinity was reported in 6 cases and 4 patients had a previous infection history. The onset of AIHA was progressive in 9 cases, marked by an anemic syndrome and hemolysis symptoms in 6 and 8 cases, respectively. The clinical triad (pallor, jaundice and splenomegaly) was found in only 4 cases. At the time of diagnosis, the median hemoglobin (Hb) level was 6g/dL (range: 4.2 to 9.2g/dL), anemia was non-regenerative in 2 patients. Thrombocytopenia and neutropenia were noted in 5 and 1 patient, respectively. Peripheral smear examination showed spherocytosis in 2 cases. All the patients had a positive DAT. Of these, 10 were positive with IgG and 3 with both IgG and C3d. AIHA was secondary to other conditions in 9 patients: infection (3 cases), autoimmune disease (4 cases), and immunodeficiency (2 cases). All the patients received first-line corticosteroid therapy but only 8 of them required blood transfusions due to severe anemia. Complete remission was obtained in 7 cases. Corticosteroid resistance and dependence were noted in 1 and 2 cases, respectively. During evolution, additional therapy was indicated in 4 patients and it included cyclosporine A, azathioprine, and mycophenolate mofetil (MMF). After a median follow-up of 4.5 years, the cure rate was 80% and only 1 patient (a boy) died due to his underlying pathology. CONCLUSION: Our study highlights the rarity, severity, and heterogeneity of etiological contexts of AIHA in children. The therapeutic difficulties justify specific expertise in pediatric hematology.

Potential hepatoprotective effect of Cheatomorpha gracilis extract against High Fat Diet (HFD)-Induced Liver Damage, and its characterization by HPLC / Efeito hepatoprotetor potencial do extrato de Cheatomorpha gracilis contra dano hepático induzido por dieta alta em gordura (HFD), e sua caracterização por HPLC

The current investigation was carried out to estimate the protective effect of aqueous extract of Cheatomorpha gracilis (AEC) against High fat Diet (HFD) induced liver damage in mice. The results of the in vitro study showed that AEC have higher antioxidant capacities in the DPPH and hydroxyl radical-scavenging assays. Indeed, many phenolic compounds (gallic acid, quercetin, naringenin, apigenin, kaempferol and rutin) were identified in the AEC. In the animal studies, during 6 weeks, HFD promoted oxidative stress with a rise level of malonaldehyde (MDA), protein carbonyls (PCOs) levels and a significant decrease of the antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase. Interestingly, the treatment with AEC (250 mg/kg body weight) significantly reduced the effects of HFD disorders on some plasmatic liver biomarkers (AST, ALT and ALP) in addition to, plasmatic proteins inflammatory biomarkers (α2 and β1 decreases / β2 and γ globulins increases). It can be suggest that supplementation of MECG displays high potential to quench free radicals and attenuates high fat diet promoted liver oxidative stress and related disturbances.

A presente investigação foi realizada para estimar o efeito protetor do extrato aquoso de Cheatomorpha gracilis (AEC) contra o dano hepático induzido por dieta rica em gordura (HFD) em camundongos. Os resultados do estudo in vitro mostraram que os AEC têm maiores capacidades antioxidantes nos ensaios DPPH e de eliminação de radicais hidroxila. De fato, muitos compostos fenólicos (ácido gálico, quercetina, naringenina, apigenina, kaempferol e rutina) foram identificados no AEC. Nos estudos em animais, durante 6 semanas, HFD promoveu estresse oxidativo com aumento do nível de malonaldeído (MDA), níveis de proteína carbonil (PCOs) e diminuição significativa das atividades de enzimas antioxidantes como superóxido dismutase, catalase e glutationa peroxidase. Curiosamente, o tratamento com AEC (250 mg / kg de peso corporal) reduziu significativamente os efeitos dos distúrbios de HFD em alguns biomarcadores hepáticos plasmáticos (AST, ALT e ALP), além de biomarcadores inflamatórios de proteínas plasmáticas (reduções α2 e β1 / β2 e γ aumenta as globulinas). Pode-se sugerir que a suplementação de MECG apresenta alto potencial para extinguir os radicais livres e atenua o estresse oxidativo do fígado promovido pela dieta rica em gordura e distúrbios relacionados.

Potential Hepatoprotective Effect of Cheatomorpha gracilis extract against High Fat Diet (HFD)-Induced Liver Damage, and its characterization by HPLC

Abstract The current investigation was carried out to estimate the protective effect of aqueous extract of Cheatomorpha gracilis (AEC) against High fat Diet (HFD) induced liver damage in mice. The results of the in vitro study showed that AEC have higher antioxidant capacities in the DPPH and hydroxyl radical-scavenging assays. Indeed, many phenolic compounds (gallic acid, quercetin, naringenin, apigenin, kaempferol and rutin) were identified in the AEC. In the animal studies, during 6 weeks, HFD promoted oxidative stress with a rise level of malonaldehyde (MDA), protein carbonyls (PCOs) levels and a significant decrease of the antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase. Interestingly, the treatment with AEC (250 mg/kg body weight) significantly reduced the effects of HFD disorders on some plasmatic liver biomarkers (AST, ALT and ALP) in addition to, plasmatic proteins inflammatory biomarkers (2 and 1 decreases / 2 and globulins increases). It can be suggest that supplementation of MECG displays high potential to quench free radicals and attenuates high fat diet promoted liver oxidative stress and related disturbances.

Resumo A presente investigação foi realizada para estimar o efeito protetor do extrato aquoso de Cheatomorpha gracilis (AEC) contra o dano hepático induzido por dieta rica em gordura (HFD) em camundongos. Os resultados do estudo in vitro mostraram que os AEC têm maiores capacidades antioxidantes nos ensaios DPPH e de eliminação de radicais hidroxila. De fato, muitos compostos fenólicos (ácido gálico, quercetina, naringenina, apigenina, kaempferol e rutina) foram identificados no AEC. Nos estudos em animais, durante 6 semanas, HFD promoveu estresse oxidativo com aumento do nível de malonaldeído (MDA), níveis de proteína carbonil (PCOs) e diminuição significativa das atividades de enzimas antioxidantes como superóxido dismutase, catalase e glutationa peroxidase. Curiosamente, o tratamento com AEC (250 mg / kg de peso corporal) reduziu significativamente os efeitos dos distúrbios de HFD em alguns biomarcadores hepáticos plasmáticos (AST, ALT e ALP), além de biomarcadores inflamatórios de proteínas plasmáticas (reduções 2 e 1 / 2 e aumenta as globulinas). Pode-se sugerir que a suplementação de MECG apresenta alto potencial para extinguir os radicais livres e atenua o estresse oxidativo do fígado promovido pela dieta rica em gordura e distúrbios relacionados.

Potential Hepatoprotective Effect of Cheatomorpha gracilis extract against High Fat Diet (HFD)-Induced Liver Damage, and its characterization by HPLC / Efeito Hepatoprotetor Potencial do Extrato de Cheatomorpha gracilis contra Dano Hepático Induzido por Dieta Alta em Gordura (HFD), e sua caracterização por HPLC

The current investigation was carried out to estimate the protective effect of aqueous extract of Cheatomorpha gracilis (AEC) against High fat Diet (HFD) induced liver damage in mice. The results of the in vitro study showed that AEC have higher antioxidant capacities in the DPPH and hydroxyl radical-scavenging assays. Indeed, many phenolic compounds (gallic acid, quercetin, naringenin, apigenin, kaempferol and rutin) were identified in the AEC. In the animal studies, during 6 weeks, HFD promoted oxidative stress with a rise level of malonaldehyde (MDA), protein carbonyls (PCOs) levels and a significant decrease of the antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase. Interestingly, the treatment with AEC (250 mg/kg body weight) significantly reduced the effects of HFD disorders on some plasmatic liver biomarkers (AST, ALT and ALP) in addition to, plasmatic proteins inflammatory biomarkers (α2 and ß1 decreases / ß2 and γ globulins increases). It can be suggest that supplementation of MECG displays high potential to quench free radicals and attenuates high fat diet promoted liver oxidative stress and related disturbances.

A presente investigação foi realizada para estimar o efeito protetor do extrato aquoso de Cheatomorpha gracilis (AEC) contra o dano hepático induzido por dieta rica em gordura (HFD) em camundongos. Os resultados do estudo in vitro mostraram que os AEC têm maiores capacidades antioxidantes nos ensaios DPPH e de eliminação de radicais hidroxila. De fato, muitos compostos fenólicos (ácido gálico, quercetina, naringenina, apigenina, kaempferol e rutina) foram identificados no AEC. Nos estudos em animais, durante 6 semanas, HFD promoveu estresse oxidativo com aumento do nível de malonaldeído (MDA), níveis de proteína carbonil (PCOs) e diminuição significativa das atividades de enzimas antioxidantes como superóxido dismutase, catalase e glutationa peroxidase. Curiosamente, o tratamento com AEC (250 mg / kg de peso corporal) reduziu significativamente os efeitos dos distúrbios de HFD em alguns biomarcadores hepáticos plasmáticos (AST, ALT e ALP), além de biomarcadores inflamatórios de proteínas plasmáticas (reduções α2 e ß1 / ß2 e γ aumenta as globulinas). Pode-se sugerir que a suplementação de MECG apresenta alto potencial para extinguir os radicais livres e atenua o estresse oxidativo do fígado promovido pela dieta rica em gordura e distúrbios relacionados.

[TAFRO syndrome and monoclonal gammapathy: Uncommon association!]. / Syndrome de TAFRO et gammapathie monoclonale : association inhabituelle !

Castleman's disease is a lymphoproliferative disorder characterized by angiofollicular lymph node hyperplasia. Recently, a new variant of multicentric Castleman's disease has been identified in Japan called TAFRO syndrome. It is characterized by a constellation of symptoms: thrombocytopenia, anasarca, reticulin fibrosis of the bone marrow, renal dysfunction and organomegaly (TAFRO). It is usually associated with polyclonal hyperimmunoglobulinemia. Here, we report the first and unique case of TAFRO syndrome with monoclonal gammapathy.

[Bladder leiomyosarcoma: report of a case]. / Léiomyosarcome de la vessie: à propos d'un cas.

Leiomyosarcoma of the urinary bladder is an extremely rare disease. In this study, which also includes a review of the literature, a new case of urinary bladder leiomyosarcoma has been reported in a 65-year old male, which was detected during an investigation of total hematuria accompanied by burning upon micturition. The clinical examination was normal, but ultrasonography followed by bladder endoscopy showed the presence of a large bladder tumor. The definitive diagnosis of this type of tumor can only be made after histological and immunohistochemical investigation, and to avoid unnecessary surgery it is essential to first differentiate it from an inflammatory pseudosarcoma. Although in the present study the outcome following total cystoprostatectomy was favorable at 3 months follow-up, in general the prognosis is uncertain due to the potentially invasive character of this type of tumor. Given the limited number of studies on the subject treatment still remains controversial, but is essentially based on surgical excision, possibly with adjuvant chemotherapy.

[Retroperitoneal schwannoma. Diagnostic and therapeutic outcome]. / Schwannome rétropéritonéal. Démarche diagnostique et thérapeutique.

Two cases of retroperitoneal benign schwannoma are described with a review of literature. Are analysed the clinical and anatomopathologic features of this rare tumor and the methods of diagnosis. The treatment is the surgical ablation of the tumor commonly easy and complete. When malignancy is established, adjuvant procedures add little to life expectancy and total surgery is done likely to be effective.