Lipid distributions in the Global Diagnostics Network across five continents.

AIMS: Lipids are central in the development of cardiovascular disease, and the present study aimed to characterize variation in lipid profiles across different countries to improve understanding of cardiovascular risk and opportunities for risk-reducing interventions. METHODS AND RESULTS: This first collaborative report of the Global Diagnostics Network (GDN) evaluated lipid distributions from nine laboratory organizations providing clinical laboratory testing in 17 countries on five continents. This cross-sectional study assessed aggregated lipid results from patients aged 20-89 years, tested at GDN laboratories, from 2018 through 2020. In addition to mean levels, the World Health Organization total cholesterol risk target (<5.00 mmol/L, <193 mg/dL) and proportions in guideline-based low-density lipoprotein cholesterol (LDL-C) categories were assessed. This study of 461 888 753 lipid results found wide variation by country/region, sex, and age. In most countries, total cholesterol and LDL-C peaked at 50-59 years in females and 40-49 years in males. Sex- and age-group adjusted mean total cholesterol levels ranged from 4.58 mmol/L (177.1 mg/dL) in the Republic of Korea to 5.40 mmol/L (208.8 mg/dL) in Austria. Mean total cholesterol levels exceeded the World Health Organization target in Japan, Australia, North Macedonia, Switzerland, Germany, Slovakia, and Austria. Considering LDL-C categories, North Macedonia had the highest proportions of LDL-C results >4.91 mmol/L (>190 mg/dL) for both females (9.9%) and males (8.7%). LDL-C levels <1.55 mmol/L (<60 mg/dL) were most common among females in Canada (10.7%) and males in the UK (17.3%). CONCLUSION: With nearly a half billion lipid results, this study sheds light on the worldwide variability in lipid levels, which may reflect inter-country differences in genetics, lipid testing, lifestyle habits, and pharmacologic treatment. Despite variability, elevated atherogenic lipid levels are a common global problem, and these results can help inform national policies and health system approaches to mitigate lipid-mediated risk of cardiovascular disease.

Review: Endophytic microbes and their potential applications in crop management.

Endophytes are microbes (mostly bacteria and fungi) present asymptomatically in plants. Endophytic microbes are often functional in that they may carry nutrients from the soil into plants, modulate plant development, increase stress tolerance of plants, suppress virulence in pathogens, increase disease resistance in plants, and suppress development of competitor plant species. Endophytic microbes have been shown to: (i) obtain nutrients in soils and transfer nutrients to plants in the rhizophagy cycle and other nutrient-transfer symbioses; (ii) increase plant growth and development; (iii) reduce oxidative stress of hosts; (iv) protect plants from disease; (v) deter feeding by herbivores; and (vi) suppress growth of competitor plant species. Because of the effective functions of endophytic microbes, we suggest that endophytic microbes may significantly reduce use of agrochemicals (fertilizers, fungicides, insecticides, and herbicides) in the cultivation of crop plants. The loss of endophytic microbes from crop plants during domestication and long-term cultivation could be remedied by transfer of endophytes from wild relatives of crops to crop species. Increasing atmospheric carbon dioxide levels could reduce the efficiency of the rhizophagy cycle due to repression of reactive oxygen used to extract nutrients from microbes in roots. © 2019 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Comparison of clonidine and fentanyl as adjuvant to ropivacaine in spinal anesthesia in lower abdominal surgeries.

BACKGROUND: Ropivacaine, a newer local anesthetic, is gaining increased acceptance due to its improved safety profile over bupivacaine and lignocaine. Analgesic adjuvants have proved to be valuable in improving the quality of anesthesia and duration of analgesia. AIM: To compare the efficacy of clonidine and fentanyl as adjuvants to ropivacaine in spinal anesthesia in lower abdominal surgeries. MATERIALS AND METHODS: A randomized, double-blind control study was carried out in 100 patients who were randomly divided into two groups. Ropivacaine-clonidine group (RC) received 30 µg of clonidine with 18.75 mg of 0.75% isobaric ropivacaine, Ropivacaine-fentanyl group (RF) received 25 µg of fentanyl with 18.75 mg of 0.75% isobaric ropivacaine intrathecally. The onset and duration of sensory and motor block, hemodynamic parameters, quality of surgical analgesia, total analgesia time, sedation score, and side effects were statistically analyzed using SPSS statistical package, paired and unpaired t-tests and Chi-square test. RESULTS: The duration of sensory block in RC (240.00 ± 20.99), RF (196.80 ± 18.34), and motor block in RC (192.20 ± 17.36), RF (139.20 ± 17.93) outlasted the duration of surgery. In clonidine group, there was significant prolongation of sensory block, motor block and the total analgesia time. Hypotension and bradycardia occurred more commonly in RC group, whereas pruritus was more in RF group. CONCLUSION: Ropivacaine when combined with either clonidine or fentanyl provided an adequate subarachnoid block for lower abdominal surgeries. As an adjuvant, clonidine has advantage over fentanyl as it increased the duration of the subarachnoid block and the postoperative analgesia.

Selection of excipients for extended release formulations of glipizide through drug-excipient compatibility testing.

For the development of extended release formulations of glipizide, techniques of thermal and isothermal stress testing (IST) were used to assess the compatibility of glipizide with selected excipients. Initially, differential scanning calorimeter (DSC) was used to evaluate the compatibility. IR spectrum of drug-excipient mixture was also compared with that of pure drug and excipient. Compatibility of excipients defined in the prototype formula was tested using IST. Based on the DSC results alone, magnesium stearate, meglumine, TRIS buffer, and lactose, were found to exhibit interaction with glipizide. Stressed binary mixtures (stored at 50 degrees C for 3 weeks) of glipizide and meglumine showed yellow coloration indicating potential incompatibility. Based on the results of DSC, IR, and/or HPLC, excipients defined in the prototype formula were found to be compatible with glipizide. The optimized formulation developed using the compatible excipients were found to be stable after 3 months of accelerated stability studies (40 degrees C and 75% RH). Overall, compatibility of excipients with glipizide was successfully evaluated using the combination of thermal and IST methods and the formulations developed using the compatible excipients was found to be stable.

Anesthesiologist: The silent force behind the scene.

The Anesthesiologist provides continuous medical care before, during, and after operation to permit the surgeons to perform surgeries; sometimes quite challenging that could otherwise cause substantial threats to the patient's survival. Anesthesiologists, because of their combination of skills are uniquely qualified to care for dying patients suffering from end diseases like cancer. These skills include knowledge of analgesic and sedative pharmacology for the management of pain, awareness of perceptual alterations along with well-known skills in drug titration and experience with critically ill and highly anxious, often agitated patients under stressful circumstances. Anesthesiologists are physicians who provide medical care to patients in a wide variety of situations. This includes preoperative evaluation, consultation with the surgical team, creation of a plan for the anesthesia (which is different in each patient), airway management, intraoperative life support, pain control, intraoperative stabilization of all the vitals, postoperative pain management. Outside the operating room, Anesthesiologist's spectrum of action includes with general emergencies, trauma, intensive care units, acute and chronic pain management. In spite of providing these highly skilled services, Anesthesiologists are facing a lot of stress these days which predisposes them to burnout, fatigue, substance abuse, and suicide. The practice of anesthesia in Indian scenario is different as compared to the western countries. In India, the Anesthesiologists are dependent on surgeons for their work. The degree of stress faced is due to a number of factors like the type and quality of work, his/her relationship with surgeons and the support he/she receives from colleagues and family.

Osmotic pumps in drug delivery.

In recent years, novel drug delivery systems (NDDS) have been recognized as an attractive niche for the pharmaceutical and health industry. Among various NDDS, osmotic pumps have matured from their use with laboratory animals to the most reliable controlled release systems for humans. Osmotically controlled drug delivery systems use osmotic pressure for controlled delivery of active agent(s). Drug delivery from these systems, to a large extent, is independent of the physiological factors of the gastrointestinal tract. Because of their unique advantages over other types of dosage forms, osmotic pumps form a class of their own among the various drug delivery technologies, and a variety of products based on this technology are available on the market. This article is a review of different types of osmotic pumps and their role in drug delivery.

Formulation aspects in the development of osmotically controlled oral drug delivery systems.

Osmotically controlled oral drug delivery systems utilize osmotic pressure for controlled delivery of active agent(s). Drug delivery from these systems, to a large extent, is independent of the physiological factors of the gastrointestinal tract and these systems can be utilized for systemic as well as targeted delivery of drugs. The release of drug(s) from osmotic systems is governed by various formulation factors such as solubility and osmotic pressure of the core component(s), size of the delivery orifice, and nature of the rate-controlling membrane. By optimizing formulation and processing factors, it is possible to develop osmotic systems to deliver drugs of diverse nature at a pre-programmed rate. In the present review, different types of oral osmotic systems, various aspects governing drug release from these systems, and critical formulation factors are discussed.

Development and evaluation of osmotically controlled oral drug delivery system of glipizide.

Extended release formulation of glipizide based on osmotic technology was developed and evaluated. The effect of different formulation variables, namely, level of solubility modifier in the core, membrane weight gain, and level of pore former in the membrane, were studied. Drug release was found to be affected by the level of solubility modifier in the core formulation. Glipizide release was inversely proportional to the membrane weight but directly related to the initial level of pore former (PVP) in the membrane. Burst strength of the exhausted shells increased with the weight gain of the membrane. On the other hand, burst strength decreased with an increase in the level of pore former in the membrane. Drug release from the developed formulations was independent of pH and agitational intensity, but dependent on the osmotic pressure of the release media. Results of SEM studies showed the formation of pores in the membrane from where the drug release occurred. The numbers of pores were directly proportional to the initial level of pore former in the membrane. The manufacturing procedure was found to be reproducible and formulations were stable after 3 months of accelerated stability studies.

Development and evaluation of extended release formulations of isosorbide mononitrate based on osmotic technology.

Extended release formulations of isosorbide mononitrate (IMN), based on osmotic technology, were developed. Target release profile was selected and different variables were optimized to achieve the same. Formulation variables like type (PVP, PEG-4000, and HPMC) and level of pore former (0-55%, w/w of polymer), percent weight gain were found to affect the drug release from the developed formulations. Drug release was inversely proportional to the membrane weight but directly related to the initial level of pore former in the membrane. Burst strength of the exhausted shells was inversely proportional to the level of pore former, but directly affected by the membrane weight. Satisfactory burst strength (more than 320 g) was obtained when PVP was used as pore former (up to 55%, w/w of polymer) at the membrane weight of 7.5% and more. The release from the developed formulations was independent of pH and agitational intensity, but dependent on the osmotic pressure of the release media. Results of SEM studies showed the formation of pores in the membrane from where the drug release occurred. The formulations were found to be stable after 3 months of accelerated stability studies. Prediction of steady-state levels showed the plasma concentrations of IMN to be within the desired range.

A validated high performance liquid chromatographic method for analysis of isosorbide mononitrate in bulk material and extended release formulations.

A reversed phase HPLC method using C(18) column was developed for the quantitative determination of isosorbide mononitrate (IMN) in the bulk material and extended release dosage forms. The method was specific to IMN and able to resolve the drug peak from the pharmacopoeial impurities and formulation excipients. The method was accurate, precise, and linear within the desired range. In addition to analysis of assay and dissolution samples, the method was successfully used for analysis of drug-excipient compatibility samples of IMN used for development of extended release formulations in our laboratory and their subsequent stability studies. The method was also used for analysis of IMN in commercially available raw material.

Compatibility studies between isosorbide mononitrate and selected excipients used in the development of extended release formulations.

Techniques of thermal and isothermal stress testing (IST) were used to evaluate the compatibility of isosorbide mononitrate (IMN) with selected excipients used in the development of extended release formulations. In the first phase of the study, differential scanning calorimeter (DSC) was used as a tool to detect any interaction. In the next phase, excipients defined in the prototype formula were tested for their compatibility with IMN using IST. Based on the results, cellulose acetate and MCC were found to show interaction with IMN. Results of IST demonstrated incompatibility between IMN and cellulose acetate. All the excipients defined in the prototype formula were found to be compatible with IMN. Using the excipients that were found to be compatible with IMN, formulations were optimized. The optimized formulation was found to be stable after 3 months of storage at accelerated stability conditions (40 degrees C and 75% RH). In conclusion, tools of DSC, and IST were successfully employed to evaluate the compatibility of IMN with selected excipients.