Elevated serum level of interleukin (IL)-18, interferon (IFN)-gamma and soluble Fas in patients with pulmonary complications in tuberculosis

Mycobacterium tuberculosis can cause life-threatening complications in which the immune response plays an important role. This study was designed to evaluate the serum levels of interleukin-18 (IL-18), interferon-gamma (IFN-gamma) and soluble Fas (sFas) in cases with pulmonary tuberculosis due to confirmed M. tuberculosis infection. The study comprised 50 patients with M. tuberculosis classified to 13 complicated cases and 37 uncomplicated patients. A significant (P<0.05) increase was found in the serum levels of IL-18, IFN-gamma and sFas in patients compared to controls and also in complicated cases compared to uncomplicated ones. Moreover, a positive significant correlation was found between serum levels of sFas with IL-18 (r=0.532, P<0.001), and with IFN-gamma (r=0.37, P=0.008) and lastly between serum levels of IL-18 with IFN-gamma (r=-0.612, P<0.001). It is concluded from these results with the recent observations that IFN-gamma levels are elevated after successful MTB treatment, suggest the possibility of enhanced Fas expression and then stimulating the infected macrophages to show an increased FasL-induced apoptosis. Modulation of FasL system by M. tuberculosis might represent an escape mechanism to evade the effect of apoptosis. Moreover, the elevated serum levels of IL-18, IFN-gamma and sFas can be considered as pathognomonic markers suggesting pulmonary tuberculosis especially in complicated cases.     

Design and In Vitro/In Vivo Evaluation of Novel Mucoadhesive Buccal Discs of an Antifungal Drug: Relationship Between Swelling, Erosion, and Drug Release

Two groups of fluconazole mucoadhesive buccal discs were prepared: (a) Fluconazole buccal discs prepared by direct compression containing bioadhesive polymers, namely, Carbopol 974p (Cp), sodium carboxymethyl cellulose (SCMC), or sodium alginate (SALG) in combination with hydroxypropyl methylcellulose (HPMC) or hydroxyethyl cellulose (HEC). (b) Fluconazole buccal discs prepared by freeze drying containing different polymer combinations (SCMC/HPMC, Cp/HPMC, SALG/HPMC, and chitosan/SALG). The prepared discs were evaluated by investigating their release pattern, swelling capacity, mucoadhesion properties, and in vitro adhesion time. In vivo evaluation of the buccal disc and in vivo residence times were also performed. Fluconazole salivary concentration after application of fluconazole buccal systems to four healthy volunteers was determined using microbiological assay and high-performance liquid chromatography. SCMC/HPMC buccal disc prepared by direct compression could be considered comparatively superior mucoadhesive disc regarding its in vitro adhesion time, in vivo residence time, and in vitro/in vivo release rates of the drug. Determination of the amount of drug released in saliva after application of the selected fluconazole disc confirmed the ability of the disc to deliver the drug over a period of approximately 5 h and to reduce side effects and possibility of drug interaction encountered during systemic therapy of fluconazole, which would be beneficial in the case of oral candidiasis.     

Monoamine oxidase A and B inhibiting effect and molecular modeling of some synthesized coumarin derivatives

New series of bioactive 7-oxycoumarin derivatives were synthesized and tested for their in vitro and in vivo monoamine oxidase (MAO) A and B inhibitory effect. In vitro studies revealed exceptionally potent and selective MAO-A inhibitors with K_i values on a picomolar range. The acetohydrazide (3b) and the dioxopyrrolidine derivative (7b) showed the most potent in vitro and in vivo MAO inhibition activity. Moreover, molecular modeling study of the synthesized compounds into MAO-A (PDB: 2Z5X) and MAO-B (PDB: 2XFN) binding sites exhibited direct correlation between AutoDock binding affinity and% inhibition MAO-A (pM) and MAO-B (μM). In addition, the results of in vivo MAO inhibiting properties (ED₅₀) of the tested compounds revealed better direct correlation.     

Bacteria induce skin regeneration via IL-1β signaling

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Protective effect of Acorus calamus on kidney and liver functions in healthy mice

Acorus calamus (AC), is an herbal medicine commonly used as traditional practice in pharmacological applications. Present study initiated was evident to proof the hepatoprotective and nephroprotective activity with supporting histopathological status of kidneys and liver. Investigation done with the 5% (w/v) of AC dissolved in tap water (50 g/l) given for 15 days compared with control tap water to 5-7 week old C57Bl/6 mice both sexes. Renal function, liver function, biochemical and complete blood count was evaluated. AC significantly reduced food intake, body weight, also plasma concentration of electrolytes such as Na⁺, K⁺, Ca²⁺, were reduced as the excretion of electrolytes were increased in urine, significantly increased Fluid Intake, with Urinary urea, Urinary creatinine, Glomerular Filtration Rate, creatinine clearance, High-density lipoproteins, Mean Corpuscular Volume. The biochemical findings showed the hepatoprotective and histopathological changes showed the nephroprotective nature of AC by normal structure with no necrosis.