Phytochemical and Therapeutic Potential of Citrus grandis (L.) Osbeck: A Review.

Citrus grandis or Citrus maxima, widely recognized as Pomelo is widely cultivated in many countries because of their large amounts of functional, nutraceutical and biological activities. In traditional medicine, various parts of this plant including leaf, pulp and peel are used for generations as they are scientifically proven to have therapeutic potentials and safe for human use. The main objective of this study was to review the different therapeutic applications of Citrus grandis and the phytochemicals associated with its medicinal values. In this article different pharmacological properties like antimicrobial, antitumor, antioxidant, anti-inflammatory, anticancer, antiepileptic, stomach tonic, cardiac stimulant, cytotoxic, hepatoprotective, nephroprotective, and anti-diabetic activities of the plant are highlighted. The enrichment of the fruit with flavonoids, polyphenols, coumarins, limonoids, acridone alkaloids, essential oils and vitamins mainly helps in exhibiting the pharmacological activities within the body. The vitamins enriched fruit is rich in nutritional value and also has minerals like calcium, phosphorous, sodium and potassium, which helps in maintaining the proper health and growth of the bones as well as the electrolyte balance of the body. To conclude, various potential therapeutic effects of Citrus grandis have been demonstrated in recent literature. Further studies on various parts of fruit, including pulp, peel, leaf, seed and it essential oil could unveil additional pharmacological activities which can be beneficial to the mankind.

Glycemic Control after Initiating Direct-Acting Antiviral Agents in Patients with Hepatitis C Virus and Type 2 Diabetes Mellitus Using the United States Integrated Healthcare System.

OBJECTIVE: Hepatitis C virus (HCV) has an increased risk of Type 2 diabetes mellitus (T2DM). Prior studies found that the eradication of HCV with direct-acting antiviral (DAA) agents led to improved glycemic control in patients with T2DM. We aimed to identify the association between HCV eradication and glycemic control in patients diagnosed with HCV and T2DM. METHODS: A retrospective observational study was conducted to identify adult patients diagnosed with HCV from January 1, 2014, to August 31, 2017. Patients were included if they were initiated on one of the following DAA agents within the study period: Sofosbuvir/velpatasvir, sofosbuvir/ledispavir, elbasvir/grazopevir. Patients were also required to have the diagnosis of T2DM. The primary outcome of this study was the average change in glycosylated hemoglobin (HbA1c) pre- versus post-DAA agents. FINDINGS: Our final cohort consisted of 996 patients diagnosed with HCV and T2DM: Patients who achieved sustained virologic response (SVR) (n = 937, 94%) and those who did not achieve SVR (n = 59, 6%). In the SVR group, there was a 0.3950% reduction in HbA1c (P < 0.0001) and in those who did not achieve SVR group, there was 0.3532% reduction in HbA1c (P = 0.0051). In the overall study population, SVR group had 0.04% more reduction in HbA1c but was not statistically significant (P = 0.7441). CONCLUSION: Both groups had statistically significant reductions in HbA1c when comparing the mean change in average HbA1c pre-versus post-DAA agent. Patients who achieved SVR had a greater absolute reduction in HbA1c by 0.04%; however, this was not statistically significant.

A mixed (long- and medium-chain) triglyceride lipid emulsion extracts local anesthetic from human serum in vitro more effectively than a long-chain emulsion.

BACKGROUND: Lipid emulsion infusion reverses cardiac toxicity of local anesthetics. The predominant effect is likely creation of a "lipid sink." This in vitro study determined the extent to which Intralipid® (Fresenius Kabi, Uppsala, Sweden) and Lipofundin® (B. Braun Melsungen AG, Melsungen, Germany) sequester anesthetics from serum, and whether it varies with pH. METHODS: Bupivacaine, ropivacaine, and mepivacaine were added to human drug-free serum (pH 7.4) at 10 µg/ml. The lipid emulsions were added, and the mixture shaken and incubated at 37°C. Lipid was removed by ultracentrifugation and drug remaining in the serum measured. Additional experiments were performed using 100 µg/ml bupivacaine and at pH 6.9. RESULTS: Lipofundin® extracted all three anesthetics to a greater extent than Intralipid® (34.7% vs..22.3% for bupivacaine, 25.8% vs..16.5% for ropivacaine, and 7.3% vs..4.7% for mepivacaine). By increasing either concentration of bupivacaine or lipid, there was an increase in drug extraction from serum. Adjusting the pH to 6.9 had no statistically significant effect on the percentage of bupivacaine sequestered. CONCLUSIONS: Bupivacaine, ropivacaine, and mepivacaine were sequestered to an extent consistent with their octanol:water partition constants (logP). In contrast with previous studies of extraction of lipids from buffer solutions, an emulsion containing 50% each of medium- and long-chain triglycerides extracted local anesthetics to a greater extent from human serum than one containing exclusively long-chain triglycerides, calling into question recent advanced cardiac life support guidelines for resuscitation from anesthetic toxicity that specify use of a long-chain triglyceride. The current data also do not support recent recommendations to delay administration until pH is normalized.

Partition constant and volume of distribution as predictors of clinical efficacy of lipid rescue for toxicological emergencies.

CONTEXT: Lipid infusion is useful in reversing cardiac toxicity of local anesthetics, and recent reports indicate it may be useful in resuscitation from toxicity induced by a variety of other drugs. While the mechanism behind the utility of lipid rescue remains to be fully elucidated, the predominant effect appears to be creation of a "lipid sink". OBJECTIVE: Determine whether the extraction of drugs by lipid, and hence the clinical efficacy of lipid rescue in toxicological emergencies can be predicted by specific drug properties. MATERIALS AND METHODS: Each drug investigated was added individually to human drug-free serum. Intralipid® was added to this drug-containing serum, shaken and then incubated at 37°C. The lipid was removed by ultracentrifugation and the concentration of drug remaining in the serum was measured by high-pressure liquid chromatography. RESULTS: In this in vitro model, the ability of lipid emulsion to bind a drug was largely dependent upon the drug's lipid partition constant. Additionally, using a multiple linear regression model, the prediction of binding could be improved by combining the lipid partition constant with the volume of distribution together accounting for approximately 88% of the variation in the decrease in serum drug concentration with the administration of lipid emulsion. CONCLUSIONS: The lipid partition constant and volume of distribution can likely be used to predict the efficacy of lipid infusion in reversing the cardiac toxicity induced by anesthetics or other medications.

Serum verapamil concentrations before and after Intralipid® therapy during treatment of an overdose.

CONTEXT. Intralipid® infusion is useful in reversing cardiac and central nervous system toxicity of local anesthetic drugs, and recent reports suggest utility in other drug overdoses. CASE DETAILS. A 47-year-old man presented to the emergency department with hypotension and complete heart block 3 h after a sustained-release verapamil overdose. He was given supportive care including calcium and hyperinsulinemia/euglycemia therapy. Nineteen and 29 h post-ingestion, Intralipid® was administered as a bolus, followed by an infusion. OBJECTIVE. The objective of this study was to determine the serum verapamil concentrations before and after Intralipid® administration and to ascertain its clinical effects. DISCUSSION. It was found that administration of Intralipid® was followed by a decrease in verapamil concentration once the lipid had been removed from the sample, demonstrating that Intralipid® was effective in sequestering verapamil, effectively removing it from the serum, and supporting its use in the treatment of verapamil overdose. Intralipid® administration was associated with an increase in the patient's blood pressure, but because other vasoactive drugs were given at the same time, it was difficult to determine its relative contribution to clinical improvement.