DISSOLUTION ENHANCEMENT AND FORMULATION OF FILM COATED TABLETS OF LORNOXICAM BY PHASE TRANSITION METHOD: IN VITRO AND IN VIVO EVALUATION

Objective: This study aimed to enhance the oral solubility and dissolution of poorly soluble lornoxicam by anti-solvent precipitation, and the manufacture of oral tablets by the phase transition method.  Methods: The solvent was mixture of polyethylene glycol 400 and absolute ethanol. Three stabilizers Inutec SP1, Pluronic F127, Sucrose ester S1670 at two concentrations and two matrix formers Mannitol, and Avicel PH102 were used to obtain 12 formulae. The formulae were characterized regarding their infrared spectroscopy (IR), differential scanning calorimetry (DSC), particle size (PS) measurement, drug content and dissolution. Further characterizations were done for the optimum formula by scanning electron microscopy (SEM) and X-ray diffraction (XRD). Four tablet formulae were manufactured by phase transition method. The optimum tablets (T3) were evaluated through hardness, drug content, disintegration, dissolution, IR, and stability studies. Finally, (T3) was compared to conventional tablets in New Zealand rabbits using crossover design. Results: The dissolution rate for the prepared formulae was enhanced, from 3.44 to 5.96 folds. Statistical significance was obtained using one and two way ANOVA among formulae. The optimum tablet formula (T3) had hardness 5.637±1.57 kg, drug content 90.424±1.19%, disintegration time 341.5±9.62 s and the drug dissolved 72.107±0.0025%. Stability, after one month storage of the selected tablets at (25 °c/60% relative humidity), was satisfactory. The absorption extent of lornoxicam from (T3) compared to the conventional tablets was higher. Conclusion: Taken together, the obtained results confirmed successfully the potential of the promising formula (T3), over the conventional tablets of lornoxicam

Added value of diffusion-weighted magnetic resonance imaging in characterization and staging of rectal cancer

Background: Approximately 15% of all cancers are found in the rectum. Rectal cancer is one of the most common malignant tumors in patients. According to the National Cancer Institute, it's the third most frequent cancer in males and the second most prevalent cancer in women. About 96 percent of all colon cancers are adenocarcinomas, with lymphoma, gastrointestinal stromal tumors, and carcinoid among the more uncommon malignancies.Aim of the study: to discuss the accuracy of MRI at staging cancer rectum using high-resolution MRI sequences and to give a brief review about more emerging important aspects of rectal cancer staging, such as the circumferential resection margin, extramural vascular invasion, and the staging of low rectal cancers.Patients and Methods: Our study was done in the Radiodiagnosis Department, Zagazig University Hospital, with 24 patients with primary rectal cancer referred from the Surgery Department for preoperative local staging of cancer rectum; the results of MRI were compared to pathologic findings.Results: Patients included in the study were 16 females and eight males; their ages ranged from 45 to 75 years with a mean age of 60 years. Adenocarcinoma comprised about 83.3 % of all of our cases. T3 and N1 tumors were found to be the most common stages in our cases.Conclusion: Preoperative MRI utilizing high-resolution sequences is an accurate modality for preoperative grading of rectal carcinoma, delineation of affection of mesorectal fascia, circumferential resection margin, and extramural vascular invasion

Sinteza novih derivata testosterona sa supstituiranim pirazolinskim prstenom kao inhibitori 5alpha-reduktaze

Condensation of 3β-hydroxy-16-[(4-chlorophenyl)methylene]androst-5-en-17-one 1 with hydrazine hydrate in acetic acid afforded N-acetyl pyrazoline derivative 2, while, condensation of 1 with semicarbazide afforded compound 3. Also, compound 1 was treated with hydrazine hydrate in absolute methanol or ethanol to afford the corresponding -methoxy (4) and -ethoxy (5) derivatives, which were cyclized with etherated boron trifluoride to the pyrazoline derivative 6. The later could be prepared directly by refluxing of 1 with hydrazine hydrate in dioxane. Oxidation of compound 6 with Oppenour or Moffat oxidizing agents yielded 3-oxo-derivatives 7 and 8, respectively. On the other hand, condensation of compound 1 with substituted hydrazines, gave the corresponding 3beta-hydroxyandrostenopyrazolines 9a,b, which were oxidized using Moffat method give 3-oxo-androstenopyrazolines 10a,b, which were condensed with ethylene triphenyl-phosphorane in DMSO to yield 3-ethylene androstenopyrazolines 11a,b. Dehydrogenation of 9a,b with Wettestein oxidation afforded 4,6-diene-3-one analogues 12a,b, which were treated with chloranil to yield delta4,6,8(14)-triene-3-one analogues 13a,b. Oppenour oxidation of 9a,b afforded Δ4-ene-3-one analogues 14a,b, which were treated with dichlorodicyanoquinone (DDQ) in dioxane to give Δ1,4,6-triene-3-one analogues 15a,b. Pharmacological screening showed that many of these compounds exhibit 5alpha-reductase activity.Kondenzacijom 3β-hidroksi-16-[(4-klorofenil)metilen]androst-5-en-17-ona 1 s hidrazin hidratom u octenoj kiselini dobiven je derivat N-acetil pirazolina 2, a kondenzacijom 1 sa semikarbazidom priređen je spoj 3. Reakcijom spoja 1 s hidrazin hidratom u apsolutnom metanolu ili etanolu nastali su odgovarajući -metoksi (4) i -etoksi (5) derivati, koji su ciklizirani s borovim trifluoridom u derivat pirazolina 6. Isti spoj se može pripaviti izravno refluksiranjem spoja 1 s hidrazin hidratom u dioksanu. Oksidacijom spoja 6 s Oppenourovim ili Moffatovim oksidansom dobiveni su 3-okso derivati 7, odnosno 8. S druge strane, kondenzacija spoja 1 sa supstituiranim hidrazinima dala je odgovarajuće 3beta-hidroksiandrostenopirazoline 9a,b, koji su oksidirani Moffatovom metodom u 3-okso-androstenopirazoline 10a,b. Ovi produkti su dalje kondenzirani s etilen rifenil-fosforanom u DMSO u 3-etilen androstenopirazoline 11a,b. Wettesteinovom dehidrogenacijom 9a,b dobiveni su delta4,6-dien-3-on analozi 12a,b, koji su s kloranilom dali 4,6,8(14)-trien-3-on analoge 13a,b. Oppenourovom oksidacijom 9a,b dobiveni su Δ4-en-3-on analozi 14a,b, koji su s diklorodicianokinonom (DDQ) u dioksanu dali Δ1,4,6-trien-3-on analoge 15a,b. Farmakološka ispitivanja ukazuju da mnogi od sintetizirnih spojeva inhibiraju 5alfa-reduktazu

Vegetation Dynamics and Species Diversity in a Saharan Oasis, Egypt

The present study provides an analysis of the floristic composition, habitat types, vegetation structure and species diversity, elucidating the role of the environmental factors that affect species distribution in Kharga Oasis, Western Desert, Egypt. The vegetation was sampled from 89 permanently visited stands in 12 sites situated along N - S line transect across the oasis, and extending for about 185 km to cover as much as possible the physiognomic variation in habitats. Four main habitats were recognized and forming concentric zones (from inside to outside): farmlands and date-palm orchards represent the inner zone, the waste-salinized lands (not saltmarshes) in the middle zone, and the surrounding (bounding) desert in the outer zone. A total of 122 species from 35 families and 102 genera represented the flora of the study area. Poaceae, Asteraceae and Fabaceae were the major families, which constituted 47% of the total flora. Classification using Bray-Curtis cluster analysis produced 4 vegetation groups (A - D); each can be linked to a certain habitat. The arrangement of habitat zones along the first DCA axis can be noticed: outer zone (bounding desert), middle zone (waste-salinized lands) and inner zone (arable lands). On the other hand, farmlands and date-palm orchard groups were separated from each other along the second DCA axis. The relationship between the vegetation and soil variables was studied using Canonical Correspondence Analysis (CCA); it was indicated the most important environmental gradients those control the vegetation composition and the distribution pattern of species in Kharga Oasis, which were mainly related to gradients in soil moisture content and fine fractions. The present situation of Kharga Oasis urges the conservation of some old historic wells and the naturally growing open dom-palm forests before vanishing due to high human activities in the area

Protective Role of Nanocurcumin in Cyclophosphamide-induced Cardiac Toxicity in Adult Male Albino Rat: A Histological, Immunohistochemical, Biochemical Study

Background: Cyclophosphamide (CYP) is a cardiotoxic agent with antineoplastic and immunosuppressive properties. Objectives: To detect the histological, immunohistochemical, biochemical cardiac toxicity of CYP and determine the protective effectiveness of nanocurcumin on the cardiac muscle of albino rats. Material and methods: The current work used forty Wistar rats allocated into four groups; normal control (I), sham control (II), CYP-treated (III) and concomitant protective CYP + nanocurcumin (IV). Results: CYP-treated group (III) showed fragmented, disrupted cardiac myocytes with cellular infiltrates and interstitial edema. Blood vessels were dilated congested. Cardiac myocytes showed pyknosis, vacuolations and some showed karyolysis. Much improvement was observed in group IV. The area percentage of fibrous tissue, TNF-α and iNOS immunoreactivity in CYP-treated group III showed statistically significant increase in contrast to that of the control group. Use of nanocurcumin in groups IV ameliorate these changes. Biochemically, there were significant increase in means of CK-MB, cTn-1, MDA, levels and decrease of GPx activity in group III (CYP -treated group) compared to the control group. Uses of nanocurcumin has been observed to improve these changes. Conclusion: Cyclophosphamide (CYP) had deleterious effects on the histological structure of the heart, cardiac enzymes, collagen fibers deposition and myofibroblast proliferation in albino rats. Administration of nanocurcumin with CYP injection could largely ameliorate these changes

Natural Immunomodulators Treat the Cytokine Storm in SARS-CoV-2

Recently, the world has been dealing with a destructive global pandemic Coronavirus disease 2019 (COVID-19) infection, since 2020; there were millions of infections and hundreds of thousands of deaths worldwide. With sequencing generations of the virus, around 60% are expected to become infected during the pandemic. Unfortunately, no drug or vaccine has been approved because no real evidence from clinical trials in treatment was reached. According to current thinking, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mortality is caused by a cytokine storm syndrome in patients with hyper-inflammatory conditions, resulting in acute respiratory distress and finally death. In this review, we discuss the various types of natural immune-modulatory agents and their role in the management of SARS-CoV-2, and cytokine storm syndrome. For example, Polyphenols as natural products can block the binding of SARS-CoV-2 spike protein to host cell receptor ACE2, stop viral entry into the host cell and block viral RNA replication. Also, saikosaponins (A, B2, C, and D), triterpene glycosides, which are isolated from medicinal plants exert antiviral action against HCoV-22E9, and Houttuynia cordata water extract has antiviral effects on SARS-CoV. Moreover, eucalyptus oil has promising potential for COVID-19 prevention and treatment. There is an urgent need for research to improve the function of the human immune system all over the world. As a result, actions for better understanding and improving the human immune system are critical steps toward mitigating risks and negative outcomes. These approaches will be strongly recommended for future emerging viruses and pathogens

Xeno-free trans-differentiation of adipose tissue-derived mesenchymal stem cells into glial and neuronal cells.

Mesenchymal stem cells (MSCs) are undifferentiated cells that have the ability of self-renewal and trans-differentiation into other cell types. They hold out hope for finding a cure for many diseases. Nevertheless, there are still some obstacles that limit their clinical transplantation. One of these obstacles are the xenogeneic substances added in either proliferation or differentiation media with subsequent immunogenic and infectious transmission problems. In this study, we aimed to replace fetal bovine serum (FBS), the main nutrient source for MSC proliferation with xeno-free blood derivatives. We tested the effect of human activated pure platelet-rich plasma (P-PRP) and advanced platelet-rich fibrin (A-PRF) on the proliferation of human adipose derived-MSCs (AD-MSCs) at different concentrations. For the induction of MSC neural differentiation, we used human cerebrospinal fluid (CSF) at different concentrations in combination with P-PRP to effect xeno-free/species-specific neuronal/glial differentiation and we found that media with 10% CSF and 10% PRP promoted glial differentiation, while media with only 10% PRP induced a neuron-like phenotype

Nanoparticles of a pyrazolo-pyridazine derivative as potential EGFR and CDK-2 inhibitors: design, structure determination, anticancer evaluation and in silico studies

The strategic planning of this study is based upon using the nanoformulation method to prepare nanoparticles 4-SLNs and 4-LPHNPs of the previously prepared 4,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-3-amine (4) after confirming its structure with single crystal X-ray analysis. These nanoparticles exhibited promising cytotoxic activity against HepG-2, HCT-116 and MCF-7 cancer cell lines in comparison with the reference doxorubicin and the original derivative 4. Moreover, their inhibitory assessment against EGFR and CDK-2/cyclin A2 displayed improved and more favorable impact than the parent 4 and the references. Detection of their influence upon cancer biomarkers revealed upregulation of Bax, p53 and caspase-3 levels and downregulation of Bcl-2 levels. The docking simulation demonstrated that the presence of the pyrazolo[3,4-c]pyridazin-3-amine scaffold is amenable to enclosure and binding well within EGFR and CDK-2 receptors through different hydrophilic interactions. The pharmacokinetic and physicochemical properties of target 4 were also assessed with ADME investigation, and the outcome indicated good drug-like characteristics