The impact of COVID-19 on hospitalization outcomes of patients with acute myocardial infarction in the USA.

Background/study objective: The effect of the COVID-19 pandemic affected health care delivery, as it led to variable outcomes in different disease states including cardiovascular diseases. In this study, we evaluated the impact of coexisting COVID-19 on Acute Myocardial Infarction (AMI). Design/setting: We analyzed discharge records of AMI patients from the National Inpatient Sample (NIS) in the year 2020. Main outcome measures: Using propensity score matching, we assessed the impact of COVID-19 infection on the in-hospital outcomes of patients presenting with AMI. Results: There were 1154 patients with concomitant COVID-19 infection and AMI who were matched with 109,990 patients with AMI and without COVID-19. We found that patients with COVID-19 who had AMI were less likely to have dyslipidemia (64.6 % vs. 70.4 %, p < 0.001), peripheral vascular disease (2.4 % vs. 3.8 % p = 0.0017), smoking history (23.5 % vs. 28.2 % p < 0.0001) and hypertension (37.1 % vs. 40.1 % p = 0.004).COVID-19 was associated with higher hospital mortality rates (Adjusted odds ratio aOR: 2.72, CI: 2.23-3.30, p < 0.001), cardiac arrest (aOR: 1.65, 95 % CI: 1.26-2.15, p < 0.001), cardiogenic shock (aOR:1.36,95 % CI: 1.10-1.68, p = 0.004) and respiratory failure (aOR:1.81, 95 % CI: 1.55-2.11 p < 0.001) compared to AMI patients without COVID-19. There was also a significant association between coexisting COVID-19 and longer duration of hospital stay (Adjusted mean differences:1.40, 95 % CI: 1.31-1.59 p < 0.0001) in AMI patients. Conclusion: COVID-19 infection is associated with worse in-hospital mortality and cardiorespiratory complications in patients with AMI.

Bioavailability and kinetics of maprotiline.

Six male subjects received simultaneously single 50-mg oral doses of a maprotiline hydrochloride tablet and a trideuterated maprotiline hydrochloride aqueous solution. No side effects or other problems were encountered. The blood levels of unlabeled and isotope-labeled maprotiline for each subject were essentially superimposable. Peak levels, averaging about 50 ng/ml, were attained between 8 and 24 hr after drug. The biologic t1/2 (beta-phase) averaged 58 hr for the unlabeled and 60.5 hr for the labeled drug. The total areas under the curves (extended to time infinity) averaged 3,862 and 3,944 ng . hr/ml for maprotiline and trideuterated maprotiline, respectively (differences between the two are not significant). At the 95% degree of confidence the Westlake confidence limits show less than 10% differences between the formulations with respect to area under the curve data (calculated both to 168 hr and extended to time infinity), peak blood levels, and biologic t1/2s. There were no differences between formulations with respect to times of peak concentrations. Estimates were made for apparent volumes of distribution (about 1,000 l), apparent blood clearance (about 14 l/hr), lag times (about 1.42 hr for tablets and 1.31 hr for solution), and absorption rate constants (about 0.34 hr-1 for the tablets and 0.42 hr-1 for the solution).

Pharmacokinetics of phenformin in man.

Phenformin was assayed in urine, plasma, and sputum specimens, obtained from two healthy volunteers during the four-day period following oral administration of a single therapeutic dose. Approximately one third of the drug was excreted unchanged in the urine. Phenformin profiles were obtained for urinary excretion rates and for plasma and saliva concentrations. The terminal exponential declines indicate a half-life of approximately 11 hours. At 37 degrees C, plasma bound 19 per cent of added phenformin.

High-throughput quantification of the anti-leukemia drug STI571 (Gleevec) and its main metabolite (CGP 74588) in human plasma using liquid chromatography-tandem mass spectrometry.

The signal transduction inhibitor STI571 (formerly known as CGP 57148B) or Gleevec received fast track approval by the US Food and Drug Administration (FDA) for treatment of chronic myeloid leukemia (CML). STI571 is a revolutionary and promising new oral therapy for CML, which functions at the molecular level with high specificity. The dramatic improvement in efficacy compared to existing treatments prompted an equally profound increase in the pace of development of Gleevec. The duration from first dose in man to completion of the New Drug Application (NDA) filing was approximately 2.6 years. In order to support all pharmacokinetics studies with sufficient speed to meet various target dates, a semi-automated procedure using protein precipitation was developed and validated. A Tomtec Quadra 96 (Model 320) and a protein precipitation step in a 96-well plate format were utilized. A Sciex API 3000 triple quadrupole mass spectrometer with an atmospheric pressure chemical ionization interface operated in positive ion mode was used for detection. The method proved to be rugged and allowed the simultaneous quantification of STI571 and its main metabolite (CGP 74588) in human plasma. Herein, assay development, validation, and representative concentration-time profiles obtained from clinical studies are presented.

Survey amongst workers in pesticide factories.

Blood samples of 75 pesticide factory workers in Agra Division, India, were analyzed for biochemical parameters of clinical importance. About 75% of the subjects had significantly low levels of serum cholinesterase activity. Several subjects had below average blood sugar and urea values. The majority had elevated levels of serum cholesterol, phospholipid and SGOT activity. 52 workers reported general toxic symptoms. A correlation between the clinical manifestations and blood biochemical parameters has been attempted.

Metabolism, plasma or serum levels, and elimination of phenformin in guinea pigs, rats, and dogs.

14C-Phenformin hydrochloride was used for investigating the metabolism, plasma or serum levels, and elimination of the drug following 1.5-mg/kg po or iv doses to guinea pigs, rats, and dogs. The amounts of individual metabolites and unchanged drug were assessed in urine as well as in plasma or serum. The glucuronide of 1-(p-hydroxyphenethyl)biguanide was a major metabolite in the blood and urine of all three species. Guinea pig serum and urine contained a sizable quantity of unchanged drug. Dog plasma and urine had significant amounts of nonconjugated 1-(p-hydroxyphenethyl)biguanide and of an unidentified major metabolite. In all three species following intravenous drug administration, unchanged drug contributed significantly to the radioactivity found in blood and urine. The apparent half-lives of phenformin eliminateion were 0.3-0.8 day for guinea pigs and rats and 1-1.5 days for dogs. Urinary excretion data indicate apparent half-lives of approximately 1.3-1.5 days for the elimination of each of the three major metabolites in dogs.

Quantification of the anti-leukemia drug STI571 (Gleevec) and its metabolite (CGP 74588) in monkey plasma using a semi-automated solid phase extraction procedure and liquid chromatography-tandem mass spectrometry.

Signal Transduction Inhibitor 571 (STI571, formerly known as CGP 57148B) or Gleevec received fast track approval by the US Food and Drug Administration (FDA) for treatment of chronic myeloid leukemia (CML). STI571 (Gleevec) is a revolutionary and promising new oral therapy for CML, which functions at the molecular level with high specificity. The dramatic improvement in efficacy compared with existing treatments prompted an equally profound increase in the pace of development of Gleevec. The duration from first dose in man to completion of the New Drug Application (NDA) filing was less than 3 years. In addition, recently, FDA approved Gleevec for the treatment of gastrointestinal stromal tumor (GIST). In order to support all toxicokinetic (TK) studies with sufficient speed to meet various target dates, a semi-automated procedure using solid phase extraction (SPE) was developed and validated. A Packard Multi-Probe I and a SPE step in a 96-well plate format were utilized. A 3M Empore octyl (C(8))-standard density 96-well plate was used for plasma sample extraction. A Sciex API 3000 triple quadrupole mass spectrometer with an atmospheric pressure chemical ionization (APCI) interface operated in positive ion mode was used for detection. Lower limits of quantification of 1.00 and 2.00 ng/ml were attained for STI571 and its metabolite, CGP 74588, respectively. The method proved to be rugged and allowed the simultaneous quantification of STI571 and CGP 74588 in monkey plasma. Herein, assay development, validation, and representative concentration-time profiles obtained from TK studies are presented.

Chemical composition of fresh snow from Gulmarg, North India.

The chemical composition and pH of 30 fresh snow samples collected during December 1986 to May 1987 at Gulmarg (34 degrees 03' N, 74 degrees 24' E, 2655 m above mean sea level), a remote place in north India, were studied. The snow samples were, by and large, alkaline in nature and were largely influenced by non-marine aerosols. The concentrations of cations (Ca(2+), K(+) and Mg(2+)) were more than the anions (SO(2-)(4) and NO(-)(3)). Factor analysis indicated that most of the ionic components were transported into the region during the period of measurements. The transport of ionic components could be attributed to the passage of western disturbances over this region. The comparison of concentrations of anions and cations in the snow samples at Gulmarg with those reported from a few countries in the west revealed that the composition of Gulmarg snow largely differs in the concentrations of cations rather than anions. Among the cations, the concentration of Ca(2+) was high at Gulmarg and this could be responsible for buffering the pH of snow in the alkaline range.

Effect of Hibiscus rosa sinensis Linn. ethanol flower extract on blood glucose and lipid profile in streptozotocin induced diabetes in rats.

Blood glucose and total lipid levels were determined in streptozotocin induced diabetic rats after oral administration of an ethanol flower extract of Hibiscus rosa sinensis. A comparable hypoglycemic effect was evidenced from the data obtained after 7 and 21 days of oral administration of the extract and glibenclamide. Maximal diminution in blood glucose (41-46%) and insulin level (14%) was noticed after 21 days. The extract lowered the total cholesterol and serum triglycerides by 22 and 30%, respectively. The increase in HDL-cholesterol was much higher (12%) under the influence of the extract as compared to that of glibenclamide (1%). The hypoglycemic activity of this extract is comparable to that of glibenclamide but is not mediated through insulin release. Other possible mechanisms are discussed.

A preliminary investigation of the possible hypoglycemic activity of Hibiscus rosa-sinensis.

The hypoglycemic activity of an ethanol extract of Hibiscus rosa-sinensis was studied in glucose located rats. After a single dose of the extract, a slight but insignificant hypoglycemic effect was observed at 30 and 90 min. At 120 min it was mild but significant. After repeated administration of the extract (once a day for seven consecutive days) a statistically significant (P < 0.001) reduction in blood glucose levels was observed at 30, 90 and 120 min after glucose loading. The average hypoglycemic activity, after repeated administration of 250 mg kg-1 leaf extract was 81%, under similar conditions average activity of tolbutamide was 96%. At 250 mg.kg-1 the efficacy of the extract was found to be 84% of tolbutamide (100 mg.kg-1). Repeated treatment of animals either with tolbutamide a sulphonylurea or H. rosa-sinensis caused a 2-3-fold improvement in glucose tolerance as compared to those receiving only once. These data suggest that the leaf extract acts like tolbutamide and the mechanism of action may be a stimulation of pancreatic beta cells to produce more insulin or an increase of the glycogen deposition in liver. It appears that the active principle in the tested extract has the sulphonylurea skeleton in which-SO2-NH-CO-group and the substituents (S1 and S2) may be the possible active sites responsible for its hypoglycemic activity.

Hypoglycemic effect of Hibiscus rosa sinensis L. leaf extract in glucose and streptozotocin induced hyperglycemic rats.

Investigations were carried out to evaluate the effect of aqueous extract of H. rosa sinensis leaves on blood glucose level and glucose tolerance using Wistar rats. Repeated administration of the extract (once a day for seven consecutive days), at an oral dose equivalent to 250 mg kg(-1), significantly improved glucose tolerance in rats. The peak blood glucose level was obtained at 30 min of glucose load (2 g kg(-1)), thereafter a decreasing trend was recorded up to 120 min. The data exhibit that repeated ingestion of the reference drug tolbutamide, a sulphonylurea and the extract brings about 2-3 fold decrease in blood glucose concentration as compared to single oral treatment. The results clearly indicate that tolbutamide improves the glucose tolerance by 91% and extract does so only by 47%. At 250 mg kg(-1), the efficacy of the extract was 51.5% of tolbutamide (100mg kg(-1)). In streptozotocin diabetic rats, no significant effect was observed with the extract, while glibenclamide significantly lowered the glucose level up to 7 hr. These data suggest that hypoglycemic activity of H. rosa sinensis leaf extract is comparable to tolbutamide and not to glibenclamide treatment.

Effect of Aegle marmelos and Hibiscus rosa sinensis leaf extract on glucose tolerance in glucose induced hyperglycemic rats (Charles foster).

In an effort to test the hypoglycemic activity of Aegle marmelos and Hibiscus rosa sinensis in glucose induced hyperglycemic rats, their alcoholic leaf extracts were studied. Both the groups of animals receiving either. A. marmelos or H. rosa sinensis leaf extract for seven consecutive days, at an oral dose equivalent to 250 mg kg-1 showed significant improvements in their ability to utilize the external glucose load. Average blood glucose lowering caused by A. marmelos and H. rosa sinensis was 67% and 39% respectively, which shows that former significantly (p < 0.001) improves the glucose tolerance curve. The magnitude of this effect showed time related variation with both the plants. Efficacy of A. marmelos and H. rosa sinensis was 71% and 41% of glybenclamide, respectively. These data throw some light on the possible mechanism of hypoglycemic activity of both the plants. The mechanism of action could be speculated partly to increased utilization of glucose, either by direct stimulation of glucose uptake or via the mediation of enhanced insulin secretion.

Polycyclic aromatic hydrocarbons in ambient air at Agra: distribution and toxicity assessment.

Polycyclic Aromatic Hydrocarbons (PAHs) are a class of organic pollutants that are commonly found in the environment, largely due to combustion or processing of hydrocarbon fuels. PAHs are considered highly toxic for human beings and several of these compounds are carcinogenic, mutagenic and teratogenic. Human exposure to PAHs occurs principally by direct inhalation, ingestion or dermal contact as a result of the widespread presence and persistence of PAHs in the urban environment. With increasing awareness that PAHs are known and suspected carcinogens, this study was undertaken to monitor PAH compounds in Total Suspended Particulate Matter (TSPM) at the industrial site--Nunhai, Agra. For this purpose, TSPM samples were collected on glass fibre filter papers (EPM 2000) using High Volume Sampler (HVS 430) at Nunhai, Agra. 16 EPA priority PAH compounds were analyzed by a Gas Chromatograph equipped with FID detector. PAHs having high molecular weight, i.e., BghiP, BbF, DbA, BaA, BaP and IP, were the most abundant with concentrations ranging between 0.026 to 0.56 ng m(-3). The calculated mean TPAH value was 0.32 ng m(-3). The probably carcinogenic and possibly carcinogenic PAH as classified by International Agency for Research on Cancer (IARC) accounted for 42% and 38% respectively of the total PAH. The health risk associated with inhalatory exposure to PAHs was assessed on the basis of Benzo(a)pyrene concentration in air and Toxic Equivalency Factor (TEF) for individual PAH. In the present study, BaP concentrations ranged from 0.005 to 0.23 ng m(-3) with a mean value of 0.04 ng m(-3). Carcinogenic potencies for DbA and BaP in PAH mixtures based on TEF concept were 45% and 39% respectively. This underlines the importance of DbA and BaPas a surrogate compound of a PAH mixture in our environment in assessing human health risk.

Quantitative determination of the NMDA antagonist cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS 19755) in human plasma using capillary gas chromatography/mass spectrometry.

An analytical method has been developed and validated for the quantitative determination of the N-methyl-D-aspartate (NMDA) antagonist cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS 19755) in human plasma. It is a member of a new class of compounds with the potential to be neuroprotective and attenuate neuronal damage resulting from brain trauma caused by stroke and head trauma. The method is based on gas chromatography/mass spectrometry and uses stable-isotope labeled CGS 19755 as the internal standard. Samples (1 ml) were first acidified (pH 2), then extracted using a solid-phase aminopropyl ion exchange column. The drug was eluted with NH4OH and evaporated until dry. Extracts were derivatized with a mixture of pentafluoropropionic anhydride and pentafluoropropanol, and analyzed by gas chromatography/mass spectrometry. Separation was accomplished on a DB-225 capillary column (15 m x 0.32 mm) with a 0.25 micron film thickness. Mass spectrometry was carried out under negative ion ammonia chemical ionization conditions with selected ion monitoring at m/z 760 and 764 for derivatized CGS 19755 and the internal standard, respectively. Specificity was shown by the lack of interfering peaks at the retention time of CGS 19755 and internal standard. Recovery and reproducibility assessments show good accuracy, precision and linearity over the validated concentration range of 2-5000 ng ml-1.

Selected ion monitoring assay for the antidepressant maprotiline.

A procedure is described which permits the determination of maprotiline in biological fluids at concentrations ranging from 0.5 to 150 ng ml-1. It relies on the use of N-desmethylclomipramine or isotope labeled maprotiline as the internal standard, on derivatization of the secondary amines with heptafluorobutyric anhydride, and on the combined use of gas chromatography with chemical ionization mass spectrometry and computerized data handling. The assaying procedure is specific, accurate and precise. It is suitable for routine analyses and has sufficient sensitivity to permit monitoring the human blood levels expected from a single therapeutic dose for a week or longer. The method, which can monitor simultaneously isotope labeled and unlabeled maprotiline, can be used to great advantage for reducing variability problems encountered in bioavailability studies.

Quantitative determination of arecoline in plasma by gas chromatography chemical ionization mass spectrometry.

A capillary gas chromatography/mass spectrometry (GC/MS) method for the quantitative analysis of arecoline in plasma has been developed for concentrations in the range 1-50 ng ml-1. Hexadeuterated arecoline was utilized as the internal standard. The removal of drug from plasma was accomplished by a two-step liquid/liquid extraction procedure involving a wash step followed by extraction with 5% triethyl amine in ethyl acetate. The GC/MS determinations were carried out with temperature-programmed capillary GC and ammonia chemical ionization mass spectrometry. The [M + H]+ ions of both analyte and internal standard were monitored at m/z 156 and 162, respectively. The method is linear and has sufficient sensitivity, precision, accuracy and selectivity for analysis of drug levels in human plasma.

Determination of CGS 16617 and stable isotope-labeled CGS 16617, an angiotensin-converting enzyme inhibitor, in human plasma by gas chromatography/mass spectrometry.

An analytical method has been developed for the simultaneous determination of a novel orally active angiotensin-converting enzyme inhibitor (CGS 16617) and a stable isotope-labeled analog. Both compounds are isolated from human plasma using an ion-exchange column, derivatized with pentafluoropropionic anhydride and pentafluoropropanol, and analyzed by gas chromatography/mass spectrometry. After splitless injection on a methyl-silicon column, the compound is detected using negative ion chemical ionization with nitrous oxide as a reagent gas. CGS 16617 labeled with four deuteriums and two 13C is used as an internal standard. The accuracy and precision of the method, expressed as the overall mean +/- SD recovery obtained from two sets of 36 quality-control samples used during a clinical study (concentration range 0.2-100 ng ml-1 plasma), was 96.1 +/- 16.2% for unlabeled drug and 97.6 +/- 14.4% for the D4-labeled drug (concentration range 0.2-100 ng ml-1 plasma). The limit of quantification using 1 ml plasma is 0.2 ng ml-1 for both labeled and unlabeled drug.