Bioequivalence evaluation of two different controlled release matrix formulations of ketoprofen tablets in healthy malaysian volunteers

The aim of this study was to evaluate the in vivo behavior of matrix tablets formulated with ketoprofen as a model drug after oral administrations in healthy Malaysian male volunteers and to compare its rate and extent of absorption with the commercially available tablet Apo-Keto SR® as a reference product. The test formulation containing 20 % HPC (GXF) as release retardant was selected in this regards. The bioequivalence study was conducted according to a single dose, randomized, 2-treatment, 2-sequence, 2-period crossover study design on six healthy non-smoking Malaysian adult male volunteers. Plasma concentrations of ketoprofen were determined by a high-performance liquid chromatographic method with UV detection. The pharmacokinetic parameters, Tmax , Cmax , AUC0–∞, Ke , and T1/2 were determined. The 90 % confidence intervals of the mean values for the test/reference ratios were 96.89-107.03 % for AUC0–∞ and 99.64-104.62 % for Cmax , respectively. The results of this study suggest that the two preparations, the test formulation of ketoprofen 200 mg tablets were bioequivalent to the marketed reference tablet of Apo-Keto SR® 200 mg in these healthy Malaysian male volunteers. However, this study results are to be further confirmed by carrying out a pivotal biostudy using more number of subjects.Colegio de Farmacéuticos de la Provincia de Buenos Aire

The Pentose Phosphate Pathway Dynamics in Cancer and Its Dependency on Intracellular pH

The Pentose Phosphate Pathway (PPP) is one of the key metabolic pathways occurring in living cells to produce energy and maintain cellular homeostasis. Cancer cells have higher cytoplasmic utilization of glucose (glycolysis), even in the presence of oxygen; this is known as the “Warburg Effect”. However, cytoplasmic glucose utilization can also occur in cancer through the PPP. This pathway contributes to cancer cells by operating in many different ways: (i) as a defense mechanism via the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) to prevent apoptosis, (ii) as a provision for the maintenance of energy by intermediate glycolysis, (iii) by increasing genomic material to the cellular pool of nucleic acid bases, (iv) by promoting survival through increasing glycolysis, and so increasing acid production, and (v) by inducing cellular proliferation by the synthesis of nucleic acid, fatty acid, and amino acid. Each step of the PPP can be upregulated in some types of cancer but not in others. An interesting aspect of this metabolic pathway is the shared regulation of the glycolytic and PPP pathways by intracellular pH (pHi). Indeed, as with glycolysis, the optimum activity of the enzymes driving the PPP occurs at an alkaline pHi, which is compatible with the cytoplasmic pH of cancer cells. Here, we outline each step of the PPP and discuss its possible correlation with cancer

DESIGN, DEVELOPMENT, AND CHARACTERIZATION OF LORATADINE SUSTAINED RELEASED BUCCAL FILM: IN VITRO AND IN VIVO STUDY IN BEAGLE DOGS

Objective: The aim of this work was to develop and evaluate bucco-adhesive films of Loratadine (LTD) for sustained release use. Methods: Design of twelve different sustained released buccal film formulas using Carbopol, pectin, sodium alginate, glycerol, carboxymethyl cellulose (CMC), hydroxypropyl cellulose (HPC), Gelatin, Hydroxyethyl cellulose (HEC), and Hydroxypropyl methylcellulose (HPMC) as mucoadhesive polymers. Films were evaluated for physicochemical properties, thickness, swelling, moisture content, drug content, in vitro dissolution. The pharmacokinetic parameters of optimal formula were evaluated in beagle dogs. Results: The selected film formula (F6) showed accepted content and muco-adhesion properties. The in vitro release study showed prolonged release of drug from films over 10 hours in optimal formulation. The bioavailability studies performed using beagle dogs model showed that there was 113.45% increase in the AUC0-24 of selected film compared with oral market tablets. Conclusion: Bucco-adhesive films is a promising dosage form for improving the bioavailability of loratadine

Expression of ERK and Akt proteins in women with unexplained first-trimester recurrent miscarriage

Objective: Recurrent miscarriage (RM) is one of the most common clinical problems in reproduction. The aims of the current study were to evaluate the expression of ERK and Akt proteins in human trophoblastic tissue and to assess the significance of MAPK and PI3K-Akt signal pathways in the progression of unexplained recurrent miscarriage. Study design: A case-control study. Setting: Women Health Hospital, Assiut, Egypt. Materials and methods: All pregnant women presented with first-trimester inevitable miscarriage with a history of RM, defined as three or more spontaneous consecutive first-trimester miscarriages before 12 weeks’ gestation, were included in the study (RM group). Age-matched healthy women who had at least one normal pregnancy with no history of miscarriage were included as a control group at the time of delivery. A sample of trophoblastic tissue was taken for Western blot test to evaluate the level of phospho-ERK and Akt (active forms) proteins in trophoblastic tissue. Results: The study included 20 women in each group. There were non-significant differences between both groups as regards maternal age, BMI, passive smoking and family residence. There were significantly lower levels of p-ERK and p-Akt in the RM group as compared to the control group (p = 0.001). Conclusion: The activation of ERK and Akt pathway plays a significant role in RM. The data suggest that decreased expression of p-ERK and p-Akt occurs less frequently during RM may play a role in this process. This suggests that p-ERK and p-Akt may be markers of RM

The Pentose Phosphate Pathway Dynamics in Cancer and Its Dependency on Intracellular pH

The Pentose Phosphate Pathway (PPP) is one of the key metabolic pathways occurring in living cells to produce energy and maintain cellular homeostasis. Cancer cells have higher cytoplasmic utilization of glucose (glycolysis), even in the presence of oxygen; this is known as the “Warburg Effect”. However, cytoplasmic glucose utilization can also occur in cancer through the PPP. This pathway contributes to cancer cells by operating in many different ways: (i) as a defense mechanism via the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) to prevent apoptosis, (ii) as a provision for the maintenance of energy by intermediate glycolysis, (iii) by increasing genomic material to the cellular pool of nucleic acid bases, (iv) by promoting survival through increasing glycolysis, and so increasing acid production, and (v) by inducing cellular proliferation by the synthesis of nucleic acid, fatty acid, and amino acid. Each step of the PPP can be upregulated in some types of cancer but not in others. An interesting aspect of this metabolic pathway is the shared regulation of the glycolytic and PPP pathways by intracellular pH (pHi). Indeed, as with glycolysis, the optimum activity of the enzymes driving the PPP occurs at an alkaline pHi, which is compatible with the cytoplasmic pH of cancer cells. Here, we outline each step of the PPP and discuss its possible correlation with cancer

Evolution of Tumor Metabolism might Reflect Carcinogenesis as a Reverse Evolution process (Dismantling of Multicellularity)

Carcinogenesis occurs through a series of steps from normal into benign and finally malignant phenotype. This cancer evolutionary trajectory has been accompanied by similar metabolic transformation from normal metabolism into Pasteur and/or Crabtree-Effects into Warburg-Effect and finally Cannibalism and/or Lactate-Symbiosis. Due to lactate production as an end-product of glycolysis, tumor colonies acquire new phenotypes that rely on lactate as energetic fuel. Presence of Warburg-Effect indicates that some tumor cells undergo partial (if not complete) de-endosymbiosis and so cancer cells have been become unicellular microorganism (anti-Dollo’s Law) specially when they evolve to develop cannibalism as way of metabolism while oxidative types of cells that rely on lactate, as their energetic fuel, might represent extra-endosymbiosis. Thus, at the end, the cancer colony could be considered as integrated metabolic ecosystem. Proper understanding of tumor metabolism will contribute to discover potential anticancer agents besides conventional chemotherapy

Impact of the COVID-19 pandemic on patients with paediatric cancer in low-income, middle-income and high-income countries: a multicentre, international, observational cohort study

OBJECTIVES: Paediatric cancer is a leading cause of death for children. Children in low-income and middle-income countries (LMICs) were four times more likely to die than children in high-income countries (HICs). This study aimed to test the hypothesis that the COVID-19 pandemic had affected the delivery of healthcare services worldwide, and exacerbated the disparity in paediatric cancer outcomes between LMICs and HICs. DESIGN: A multicentre, international, collaborative cohort study. SETTING: 91 hospitals and cancer centres in 39 countries providing cancer treatment to paediatric patients between March and December 2020. PARTICIPANTS: Patients were included if they were under the age of 18 years, and newly diagnosed with or undergoing active cancer treatment for Acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, Wilms' tumour, sarcoma, retinoblastoma, gliomas, medulloblastomas or neuroblastomas, in keeping with the WHO Global Initiative for Childhood Cancer. MAIN OUTCOME MEASURE: All-cause mortality at 30 days and 90 days. RESULTS: 1660 patients were recruited. 219 children had changes to their treatment due to the pandemic. Patients in LMICs were primarily affected (n=182/219, 83.1%). Relative to patients with paediatric cancer in HICs, patients with paediatric cancer in LMICs had 12.1 (95% CI 2.93 to 50.3) and 7.9 (95% CI 3.2 to 19.7) times the odds of death at 30 days and 90 days, respectively, after presentation during the COVID-19 pandemic (p<0.001). After adjusting for confounders, patients with paediatric cancer in LMICs had 15.6 (95% CI 3.7 to 65.8) times the odds of death at 30 days (p<0.001). CONCLUSIONS: The COVID-19 pandemic has affected paediatric oncology service provision. It has disproportionately affected patients in LMICs, highlighting and compounding existing disparities in healthcare systems globally that need addressing urgently. However, many patients with paediatric cancer continued to receive their normal standard of care. This speaks to the adaptability and resilience of healthcare systems and healthcare workers globally