The influence of natural polymers on loratadine's solubility and dissolution profiles.

Second-generation tricyclic H1 antihistamine loratadine (LTD) has a high permeability, low water solubility, and an oral absorption rate dependent on the rate at which it dissolves in the gastrointestinal tract. One approach suggested for improving the drug's solubility and rate of dissolution is natural solid dispersion (NSD). The present study evaluated the use of hydrophilic natural polymers, sodium alginate (SA), hyaluronic acid (HA), and xyloglucan (XG), in natural solid dispersion to enhance LTD solubility and dissolution rate. A total of 12 formulations comprising varied drug-to-polymer ratios were produced and analyzed for percentage yield, water solubility, and in vitro dissolution rate. The solubility of LTD was improved in all formulations. Excellent results were achieved with NSD1 (LTD: SA 1:0.25), with a high yield (99%), superior solubility (0.187) compared to pure loratadine (0.0021), and a speedy dissolution rate (98%) within 30 minutes. These studies suggest natural polymers like SA, HA, and XG can considerably increase LTD solubility. When introduced into NSD, these polymers effectively augment LTD dissolving rates, presenting attractive prospects for better bioavailability and therapeutic efficacy.

Comparative analysis of antioxidant status in diabetic patients with and without insulin resistance.

Diabetes mellitus (DM) is a metabolic disorder characterized by insulin resistance, where hyperglycemia is believed to trigger oxidative stress, contributing to insulin function impairment. This study aimed to assess and compare levels of malondialdehyde (MDA), glutathione (GSH), and uric acid in diabetic patients with and without insulin resistance and to assess the correlation with fasting blood sugar (FBS) and lipid profiles. Significant variations were found in MDA, uric acid, and GSH levels between insulin-resistant and non-resistant diabetic groups (p<0.0001). FBS, hemoglobin A1C (HbA1C), insulin activity, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) significantly differed between the groups (p<0.0001). Total cholesterol, triglyceride, high-density lipoprotein (HDL), very-low-density lipoprotein (VLDL), and low-density lipoprotein-cholesterol (LDL-C) concentrations were higher in the insulin resistance group than the non-insulin resistance group (p<0.0001). Uric acid also exhibited a significant correlation (p<0.01) with LDL levels, while HDL levels showed a negative correlation with both MDA and uric acid (p<0.001). Diabetes mellitus, characterized by chronic hyperglycemia, may play a role in the development of oxidative stress. This oxidative stress is a significant factor that could potentially lead to the onset of insulin resistance, a condition strongly associated with dyslipidemia. The results of this study indicate that the decrease in GSH levels and the increase in MDA and uric acid levels are particularly noteworthy in the context of insulin resistance among patients with diabetes.

Inhibition of branched-chain alpha-keto acid dehydrogenase kinase augments the sensitivity of ovarian and breast cancer cells to paclitaxel.

CONTEXT: Many cancer patients who initially respond to chemotherapy eventually develop chemoresistance, and to address this, we previously conducted a RNAi screen to identify genes contributing to resistance. One of the hits from the screen was branched-chain α-keto acid dehydrogenase kinase (BCKDK). BCKDK controls the metabolism of branched-chain amino acids (BCAAs) through phosphorylation and inactivation of the branched-chain α-keto acid dehydrogenase complex (BCKDH), thereby inhibiting catabolism of BCAAs. METHODS: We measured the impact on paclitaxel sensitivity of inhibiting BCKDK in ovarian and breast cancer cell lines. RESULTS: Inhibition of BCKDK using siRNA or two chemical inhibitors (BCKDKi) was synergistic with paclitaxel in both breast and ovarian cancer cells. BCKDKi reduced levels of BCAA and the addition of exogenous BCAA suppressed this synergy. BCKDKi inactivated the mTORC1-Aurora pathway, allowing cells to overcame M-phase arrest induced by paclitaxel. In some cases, cells almost completed cytokinesis, then reverted to a single cell, resulting in multinucleate cells. CONCLUSION: BCKDK is an attractive target to augment the sensitivity of cancer cells to paclitaxel.

Electrolyte disturbances in a sample of hospitalized patients from Iraq.

Electrolyte disturbances are common in ill patients. Several conditions in the intensive care unit (ICU) might be responsible for developing electrolyte disorders, and medications may also contribute to these disturbances. The current study aimed to determine the frequency of electrolyte disturbances and assess the pattern of electrolyte imbalance in hospitalized patients, determining the possible effects of these electrolyte disorders. This cross-sectional study included patients admitted to the intensive care unit, respiratory care unit (RCU), and coronary care unit (CCU) at the Al-Sadar teaching hospital, Najaf, Iraq, from November 2020 to April 2021. The study collected data from two hundred patients regarding demographics, categories of ICUs at admission, comorbidities, and laboratory values at admission. Also, electrolyte levels at ICU admission and during hospitalization were collected from the medical database record. In addition, the patient's age, sex, fasting blood sugar (FBS), body mass index (BMI), B.urea, and creatinine were matched. Na+, K+, ionized Ca++, and Cl serum levels were significantly different during hospitalization. Comorbidities with predominant hypokalemia were found in 80.5%, hypochloremia in 73%, hypocalcaemia in 72%, and hyponatremia in 56.7% of hospitalized patients. Studying the effect of co-morbidities indicated a higher percentage (44%) of admitted patients with ischemic heart diseases, 38 (19%) with digestive diseases, 21 (10.5%) with orthopedic surgery in an emergency, 14 (7%) with pneumonia and lung diseases, 12 (6%) with diabetics, 18 (9%) with sepsis, and 9(4.5%) with seizure. Hospitalized patients may be at higher risk of developing combined electrolytes disorder associated with decreased serum levels of K+, Na+, Ca++, and Cl-. Thus, doctors and clinicians are recommended to observe electrolyte changes and correct them as they seem to negatively impact the outcome and prognosis.

Identification of foods that affect the anti-cancer activity of pitavastatin in cells.

Statins inhibit the synthesis of mevalonate, a precursor isoprenoid molecule to geranylgeraniol that is necessary for the post-translational modification of several small GTPase oncogenes. Despite numerous preclinical studies suggesting that statins can be effective anticancer agents, prospective clinical trials have failed to demonstrate any clinical benefit in patients with cancer. We previously demonstrated that geranylgeraniol suppresses the activity of statins in cell culture studies, and that pitavastatin can cause regression of ovarian cancer xenografts in mice if the animals' diet is modified to avoid the inclusion of geranylgeraniol. Dietary sources of geranylgeraniol may consequently limit the activity of statins in cancer clinical trials. The present study tested several foods to identify those that affected the cytotoxic activity of pitavastatin towards ovarian cancer cells. Solvent extracts of several foods were tested for their ability to suppress the effects of pitavastatin in cell growth assays. The results revealed that pitavastatin induced cell death in ovarian cancer cells (IC50=5.2 µM) and this was blocked by geranylgeraniol whereas other products of the mevalonate pathway (coenzyme Q, dolichol or cholesterol) had no effect on the activity of pitavastatin in cell growth assays. Solvent extracts from several foods, especially oils (apart from rapeseed), also blocked the cytotoxic activity of pitavastatin. Several extracts from a range of fruit, vegetables and carbohydrate-rich foods also did not block the activity of pitavastatin. However, extracts from beans, lettuce, oats, eggs and various nuts reduced the activity of pitavastatin. These data identified foods that patients could eat to potentially improve the outcome of clinical trials of pitavastatin in cancer.