Efficacy and safety profile of corticosteroids and non-steroidal anti-inflammatory drugs in COVID-19 management: A narrative review.

Due to the fact that coronavirus disease 2019 (COVID-19) is still prevalent, and current reports show that some parts of the world have seen increase in incidence, it is relevant that health professionals and scientists know about recent or novel trends, especially drug treatments. Additionally, the safety profiles of these drug treatments need to be documented and shared with the public. Some studies have demonstrated the clinical benefits of non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids in COVID-19 treatment. On the contrary, others have also reported that NSAIDs and corticosteroids may worsen symptoms associated with COVID-19. While some researchers have suggested that corticosteroids may be helpful if used in the early stages of COVID-19, there are still some conflicting findings regarding the use of corticosteroids in certain viral infections. Our review suggests that methylprednisolone, dexamethasone, and ibuprofen have therapeutic potential in reducing mortality due to COVID-19 among hospitalized patients. This review also highlights the fact that the use of NSAIDs is not associated with adverse outcomes of COVID-19. In reality, evidence suggests that NSAIDs do not increase the risk of COVID-19 infections. Also, the literature reviewed suggests that corticosteroid treatment in COVID-19 was linked with a decrease in all-cause mortality and disease progression, without increase in adverse events when compared to no corticosteroid treatment.

Glycine/NMDA Receptor Pathway Mediates the Rapid-onset Antidepressant Effect of Alkaloids From Trichilia Monadelpha.

INTRODUCTION: Major depressive disorder is often associated with suicidal tendencies, and this condition accentuates the need for rapid-acting antidepressants. We previously reported that Alkaloids (ALK) from Trichilia monadelpha possess antidepressant action in acute animal models of depression and that this effect is mediated through the monoamine and L-arginine-NO-cGMP pathways. This study investigated the possible rapid-onset antidepressant effect of ALK from T. monadelpha and its connection with the glycine/NMDA receptor pathway. METHODS: The onset of ALK action from T. monadelpha was evaluated using the Open Space Swim Test (OSST), a chronic model of depression. The modified forced swimming and tail suspension tests were used to assess the effect of the ALK on the glycine/NMDA receptor pathway. The Instutute of Cancer Research (ICR) mice were treated with either ALK (30-300 mg/kg, orally [PO]), imipramine (3-30 mg/kg, PO), fluoxetine (3-30 mg/kg, PO), or saline. To identify the role of glycine/NMDA receptor pathway in the effect of ALK, we pretreated mice with a partial agonist of the glycine/NMDA receptor, D-cycloserine (2.5 mg/kg, intraperitoneally [IP]), and an agonist of glycine/NMDA receptor, D-serine (600 mg/kg, IP), before ALK administration. RESULTS: ALK reversed immobility in mice after the second day of drug treatment in the OSST. In contrast, there was a delay in the effects induced by fluoxetine and imipramine. ALK also increased mean swimming and climbing scores in mice. ALK was more efficacious than imipramine and fluoxetine in reducing immobility and increasing distance traveled. It is noteworthy that ALK was less potent than fluoxetine and imipramine. D-cycloserine potentiated mobility observed in the ALK- and fluoxetine-treated mice. In contrast, D-serine decreased mobility in the ALK-treated mice. CONCLUSION: The study results suggest that ALK from T. monadelpha exhibits rapid antidepressant action in mice, and the glycine/NMDA receptor pathway possibly mediates the observed effect.

Population Pharmacokinetic Characteristics of Amikacin in Suspected Cases of Neonatal Sepsis in a Low-Resource African Setting: A Prospective Nonrandomized Single-Site Study.

BACKGROUND: Amikacin exhibits marked pharmacokinetic (PK) variability and is commonly used in combination with other drugs in the treatment of neonatal sepsis. There is a paucity of amikacin PK information in neonates from low-resource settings. OBJECTIVES: To determine the PK parameters of amikacin, and explore the influence of selected covariates, including coadministration with aminophylline, on amikacin disposition in neonates of African origin. METHODS: Neonates with suspected sepsis admitted to an intensive care unit in Accra, Ghana, and treated with amikacin (15 mg/kg loading followed by 7.5 mg/kg every 12 hours), were recruited. Serum amikacin concentration was measured at specified times after treatment initiation and analyzed using a population PK modeling approach. RESULTS: A total of 419 serum concentrations were available for 247 neonates. Mean (SD) trough amikacin concentration (from samples collected 30 minutes before the fourth dose) among term (n = 25), and preterm (<37 weeks' gestation n = 36) neonates were 6.2 (3.4) and 9.2 (5.7) µg/mL, respectively (P = 0.02). A 1-compartment model best fitted amikacin disposition, and birth weight was the most important predictor of amikacin clearance (CL) and distribution (V). The population CL and V of amikacin were related as CL (L/h) = 0.153 (birth weight/2.5)1.31, V (L) = 2.94 (birth weight/2.5)1.18. There was a high between-subject variability (58.9% and 50.7%) in CL and V, respectively. CL and V were 0.058 L/h/kg and 1.15 L/kg, respectively, for a mean birth weight of 2.1 kg, and the mean half-life (based on 1-compartment model), was 13.7 hours. CONCLUSIONS: The V and half-life of amikacin in this cohort varied from that reported in non-African populations, and the high trough and low peak amikacin concentrations in both term and preterm neonates suggest strategies to optimize amikacin dosing are required in this population.

Metformin versus Insulin in the Management of Pre-Gestational Diabetes Mellitus in Pregnancy and Gestational Diabetes Mellitus at the Korle Bu Teaching Hospital: A Randomized Clinical Trial.

OBJECTIVE: To determine if metformin monotherapy or metformin in combination with insulin is equally effective as insulin monotherapy at glycemic control in diabetes mellitus in pregnancy among Ghanaians. METHODS: This was a study involving 104 pregnant women with type 2 diabetes mellitus (T2DM) or gestational diabetes mellitus (GDM) at 20-30 weeks gestation. Participants were randomized into metformin and insulin treatment groups. Starting dose of metformin was 500 mg once a day and increased gradually over two (2) weeks, to meet glycemic targets. Insulin was added if targets could not be reached on metformin alone at maximum doses. Total daily dose of premixed insulin at initiation was calculated as 0.3 IU/kg body weight and titrated upwards to achieve glycemic control. Glycemic profile monitoring was done every two weeks. RESULTS: The two hour post prandial blood glucose (2HPG) levels were significantly lower in the metformin group than the insulin group (p= 0.004). CONCLUSION: The findings of this study suggest that metformin monotherapy is effective in achieving glycemic targets in the management of diabetes in pregnancy. It is more effective than insulin in lowering the 2HPG level. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12614000942651.

Prescribing trend of antimalarial drugs at the Ghana Police Hospital.

INTRODUCTION: Malaria ranks among the top three leading causes of morbidity and mortality in developing countries. Appropriate use of recommended antimalarial drugs is vital in the effective management of malaria. METHODOLOGY: This study sought to assess the prescribing trend of antimalarial drugs at the Ghana Police Hospital. Antimalarial drug prescribing trends from 3,127 patient cards were assessed at the pharmacy unit of the hospital between December 2012 and May 2013 using modified World Health Organization rational drug prescribing indicators. RESULTS: Of the 6,697 drugs assessed from the patient cards, antimalarial drugs prescribed included artemether-lumefantrine, 4,226 (63.1%), artemether injection with artemether-lumefantrine tablets, 1,741 (26%), artesunate injection, 241 (3.6%), artemether injection, 194 (2.9%), and artesunate-amodiaquine tablets, 188 (2.8%). The average number of drugs prescribed per encounter was 2.1. A total of 4,052 (60.5%) drugs were prescribed by their generic names, and 2,645 (39.5%) were prescribed by their brand names. There were 2,250 (33.6%) encounters with injection (33.6%), and 6,001 (89.6%) of the prescribed drugs were from the essential drugs list. Prescriptions conforming to recommended dosage regimen totaled 6,328 (94.5%). CONCLUSION: The antimalarial prescribing pattern at the hospital was generally satisfactory. However, the use of injectable antimalarials appeared to be high.

Susceptibility pattern of uropathogens to ciprofloxacin at the Ghana police hospital.

INTRODUCTION: Reports of increasing resistance of uropathogens to antimicrobials is of global concern. Culture and drug susceptibility tests remain a vital guide to effective therapy. The aim of this study was to determine the susceptibility pattern of isolated uropathogens to ciprofloxacin at the Ghana Police Hospital. METHODS: A total of 705 mid-stream urine samples were collected from patients suspected of having urinary tract infection, and visited the Ghana Police Hospital's laboratory from December 2013 to March 2014. Samples were cultured and isolates identified by standard methods, after which isolates susceptibility to ciprofloxacin was determined. RESULTS: Prevalence of urinary tract infection among patients' whose samples were analyzed was 15.9%. Predominant uropathogens isolated were E. coli (46.4%), Coliform (41.1%) and Coliform spp. with Candida (6.2%). Other isolates were Pseudomonas spp. (2.7%), Salmonella spp. (1.8%), Candida spp. (0.9%) and Klebsiella spp (0.9%). The overall resistance among the top three isolated uropathogens to ciprofloxacin was 35.9%. Resistance pattern demonstrated by respective isolates to ciprofloxacin were: E. coli (38.5%), Coliform (54.3%), and Coliform spp. with Candida (15%). The other isolates showed 100% sensitivity. CONCLUSION: This study revealed a relatively high ciprofloxacin resistance among isolated uropathogens, hence, the need for prudent prescribing and use of ciprofloxacin in urinary tract infection management.

Anti-atherogenic and anti-ischemic potentials of Croton membranaceus observed during sub-chronic toxicity studies.

BACKGROUND: Croton membranaceus (CM) is used for benign prostate hyperplasia treatment. OBJECTIVE: Sub-chronic toxicity studies are non-existent and provided the basis for this study. MATERIALS AND METHODS: 90 days oral administration of a low dose (LD) (30 mg/kg b. wt.), medium dose (MD) (150 mg/kg b. wt.), and high dose (HD) (300 mg/kg b. wt.) CM aqueous root extract to 3 groups (n=6 each) of male Sprague-Dawley rats, alongside a control group, was undertaken. Urinalysis, hepato-renal function tests, lipid profile, cardiac enzymes, and routine hematology tests were performed. RESULTS: Triglyceride levels (C=1.05±0.19, LD=0.64±0.08, MD=0.55±0.04, HD=0.50±0.02 mmol/L) were significantly reduced (P<0.05). Very low density lipoprotein (C=0.48±0.09, LD=0.29±0.04, MD=0.25±0.02, HD=0.23±0.01 mmol/L) decreased significantly (P<0.05). Cardiac enzymes-creatinine kinase (C=568±172, LD=315±79, MD=441±209, HD=286±81 IU/L) decreased markedly (P<0.05) alongside lactate dehydrogenase (C=2675±875, LD=1667±1229, MD=1186±442, HD=855±239 IU/L) (P<0.05). CONCLUSION: C. membranaceus aqueous root extract is non-toxic but demonstrates anti-atherogenic and anti-ischemic potentials.

Male rat hormone imbalance, testicular changes and toxicity associated with aqueous leaf extract of an antimalarial plant: Phyllanthus niruri.

CONTEXT: Phyllanthus niruri L. (Euphorbiaceae), a medicinal plant traditionally known for dissolving kidney stones, is used prophylactically as an antimalarial agent. OBJECTIVE: The study was undertaken to determine its effect on some male hormones and other toxicological properties due to paucity of its data despite its wide use. MATERIAL AND METHODS: Male Sprague-Dawley rats (100-140 g) were used. Group 1 [control group (C), n = 6] received water. Group 2 [low-dose test group (LD), n = 6] received 50 mg/kg body weight (b.wt.) aqueous leaf extract orally. Group 3 [high-dose test group (HD), n = 6] received 500 mg/kg b.wt. extract for 90 days. Upon sacrifice, among other organs the testes were harvested. Blood samples drawn were used for biochemical (including progesterone, estrogen and testosterone), cytotoxicity and hematological assays. RESULTS: C, LD and HD estrogen values were 192 ± 25, 385 ± 122 and 962 ± 357 pg/ml, respectively. In the same order, progesterone values were 96 ± 24, 155 ± 45 and 320 ± 80 pg/ml, respectively. Testosterone levels were 5210 ± 1090, 4710 ± 220 and 4500 ± 580 pg/ml, respectively. Significant differences were observed in the estrogen and progesterone levels (p = 0.001). Degenerative changes were observed histologically. Cytotoxicity at 50% (CC50) was 10.0 µg/ml. DISCUSSION AND CONCLUSION: This antimalarial plant is mildly cytotoxic with male antifertility properties.

In vitro activity of extract and fractions of natural cocoa powder on Plasmodium falciparum.

Several flavonoids isolated from certain plants have demonstrated antiplasmodial activity, after their initial indigenous use in malaria treatment. Cocoa has been found to be a rich food source of flavonoids in comparison with many common foods and beverages. The aim of this work was to investigate the in vitro activity of natural cocoa powder on the growth of Plasmodium falciparum. Prepared crude methanol extract was partitioned successively with petroleum ether, ethyl acetate, chloroform, and butanol. Total flavonoid concentration in the crude methanol extract and fractions was measured by the AlCl(3) colorimetric assay. Direct inhibitory activity of the natural cocoa powder was assessed by culturing extract and fractions with P. falciparum in vitro. Greater antiplasmodial activity was observed in nonpolar solvent fractions (chloroform, ethyl acetate, and petroleum ether) compared with polar solvents. The chloroform fraction was most active, with mean±SEM 50% and 90% inhibition concentrations of 48.3±0.9 and 417±7.8 µg/mL, respectively. The study showed a weak association between total flavonoid concentration and antiplasmodial activity. Early trophozoite (ring-stage) synchronized cultures treated with the chloroform fraction of natural cocoa powder showed a decline in growth. Further reduction in parasitemia was also observed for other erythrocytic stages. These results suggest that natural cocoa powder has measurable direct in vitro inhibitory effect on P. falciparum and support the anecdotal reports of its ability to prevent malaria as a result of regular intake as a beverage.

Toxicity potentials of the nutraceutical Moringa oleifera at supra-supplementation levels.

Moringa oleifera Lam. (order -Moringales, family -Moringaceae and genus -Moringa) is a well known nutraceutical used in the treatment of hypercholesterolemia and hyperglycemia, and also, as a nutritional supplementation. Its popularity use raises the question of possible toxicity at supra-supplementation levels. The objective of the study was to ascertain possible acute toxicity with supra-supplementation using Sprague-Dawley (S-D) rats. In experiment 1, human peripheral blood mononuclear cells were given graded doses of Moringa oleifera aqueous leaf extract to induce cytotoxicity. In experiment 2, two groups of rats received low and high dose (LD and HD, respectively) levels (1,000 and 3,000 mg/kgb.wt, respectively) per o.s. alongside negative and positive control rats (0.9% saline and 10mg/mL N-ethyl-N-nitrosourea - administered i.m., respectively). Each group consisted of five rats. Rats were killed after 48 h and the femur bone marrow aspirate examined for polychromatic micronucleated erythrocytes (PCEMN)/normochromatic micronucleated erythrocytes (NCEMN) ratios after Giemsa/Leishman staining. In experiment 3, control, LD and HD groups were established. The LD and HD extracts were administered per o.s. to the respective groups and observed for 14 days. Each group consisted of five rats. Blood was sampled after 48 h and 14 days and examined biochemically and haematologically for acute toxicity. Experiment 1 showed that Moringa oleifera was cytotoxic at 20mg/mL. In experiment 2, PCEMN/NCEMN ratios were: negative control=2.087; LD=1.849; HD=1.397; positive control=1.257. Statistically, LD and HD ratios were significant (p=0.020). Experiment 3 showed that hepatonephro-toxicity was nil with no abnormal haematology results. Genotoxicity results have hitherto not been shown. Moringa oleifera is genotoxic at supra-supplementation levels of 3,000 mg/kg b.wt. However, intake is safe at levels ≤ 1,000 mg/kg b.wt.

Natural cocoa ingestion reduced liver damage in mice infected with Plasmodium berghei (NK65).

PURPOSE: This study tested whether natural cocoa powder ingestion could mitigate hepatic injury coincident with murine malaria. Plasmodium berghei infection causes liver damage including hepatic sinusoidal distension, and elevated serum alanine transaminase (ALT) and aspartate transaminase (AST) levels. According to literature, these pathologies largely result from activity of reactive oxygen species (ROS) and may be extenuated by antioxidants. ANIMALS AND METHODS: Thirty Balb/c mice were randomly assigned to three equal groups. One of two groups of mice inoculated with 0.2 mL of P. berghei-parasitized red blood cells (RBCs) was given unrestricted 24-hour access to a natural cocoa powder beverage (2% by weight) in place of water. The third group of mice were neither infected nor given cocoa. All mice were fed the same standard chow. After 6 days, mice were sacrificed and their livers processed for histomorphometric assessment of mean hepatic sinusoidal diameter as a quantitative measure of altered morphology. Serum ALT and AST were measured as a gauge of functional impairment. RESULTS: Compared with uninfected mice, hepatic sinusoidal diameter in P. berghei-infected mice not given cocoa increased by 150%, whereas a smaller increase of 83% occurred in infected mice that ingested cocoa. Mean serum ALT increased by 127% in infected mice not given cocoa and 80% in infected mice that consumed cocoa, compared with the value for uninfected mice. Similarly, mean serum AST was raised by 141% in infected mice not given cocoa and 93% in infected mice that drank cocoa. CONCLUSION: Distension of hepatic sinusoidal diameter in P. berghei-infected mice was reduced by 67%, whereas respective elevations of serum ALT and AST concentrations were reduced by 47% and 48% via ingestion of cocoa. Anti-inflammatory and antioxidant components of cocoa probably mediated the demonstrated hepatoprotective benefit by blunting pernicious ROS activity in P. berghei-infected mice.

Acute toxicity studies of aqueous leaf extract of Phyllanthus niruri.

Phyllanthus niruri is a plant with medicinal properties. It is often used to treat mild malaria and the elimination of renal stones. However, studies on its toxicity are scarce. The study was carried out to determine if the aqueous leaf extract of P. niruri administered to female Sprague-Dawley rats would illicit evidence of toxicity. Fifteen female rats weighing 150-200 g were divided into 3 groups. Rats in Group 1 were given a single low dose (LD) of 2000 mg/kg b.w. of the extract by oral gavage within 24 hrs. Rats in Group 2 were given a single high dose (HD) of 5000 mg/kg b.w. of the extract by oral gavage within 24 hrs. Rats in Group 3 were not given any extract but drinking water and served as the control group (C). All the rats were observed for signs of toxidromes for 14 days. On the 15(th) day, all the rats were sacrificed. Body organs were harvested for macroscopic examination. Urine and blood samples were drawn and analyzed. Hematological tests performed included full blood count and hemoglobin. Biochemical examinations included bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein, albumin, globulin, alkaline phosphatse (ALP), γ-glutamyltranspeptidase (GGT), urea, and creatinine. The results of the three groups were not significantly different. Examination of the various body organs did not show any abnormality. Thus no toxicity was observed at the levels administered. The LD(50) of the aqueous extract is>5000 mg/kg. b.w.

Plasmodium falciparum: Assessment of Selectivity of Action of Chloroquine, Alchornea cordifolia, Ficus polita, and Other Drugs by a Tetrazolium-Based Colorimetric Assay.

A tetrazolium-based colorimetric selective assay (MTT-based CSA) was developed to assess the selectivity of antimalarial drugs. This in vitro assay, unlike all others, measures the ability of drugs to indirectly protect red blood cells (RBCs) from Plasmodium-falciparum-induced destruction. Optimum incubation time and number of cells needed were 5 days and 23 × 10(6) RBCs per well, respectively. A parasitemia range of 0.375% to 3% was found to be suitable for this assay. The MTT-based CSA determined anti-P. falciparum strain DD2 activity of chloroquine at a higher 50% effective concentration (EC(50)) value (21.0 µg/mL) than the isotopic microtest (10.0 µg/mL). Artesunate and oxytetracycline achieved 90% effect against DD2 with minimal or no toxicity to RBCs. Against chloroquine sensitive strain 3D7, chloroquine and Alchornea cordifolia had EC(50) values of 0.025 µg/mL and 4.9 µg/mL respectively, and selective index (SI) values of >2,000 and >69.4 µg/mL, respectively.

A comprehensive study of Easter lily poisoning in cats.

This study was conducted with 3 objectives in mind: first, to identify the toxic fraction (aqueous or organic) in leaves and flowers; second, to identify diagnostic marker(s) of toxicosis in cats; and, third, to evaluate the morphologic effects of intoxication. The study was conducted in 2 phases. Phase 1 was to identify which extract, organic or aqueous, was nephrotoxic and also to determine the appropriate dose for use in the phase 2 studies. Results indicated that only the aqueous extracts of leaves and flowers were nephrotoxic and pancreotoxic. To identify the proximate toxic compound, cats in the phase 2 study were orally exposed to subfractions of the aqueous flower extract, 1 subfraction per cat. Results confirmed vomiting, depression, polyuria, polydipsia, azotemia, glucosuria, proteinuria, and isosthenuria as toxic effects of the Easter lily plant. Another significant finding in serum was elevated creatinine kinase. Significant histologic kidney changes included acute necrosis of proximal convoluted tubules and degeneration of pancreatic acinar cells. Renal ultrastructural changes included swollen mitochondria, megamitochondria, edema, and lipidosis. Subfraction IIa3 of the aqueous floral extract contained most of the toxic compound(s). These studies reproduced the clinical disease, identified the most toxic fraction of the Easter lily, and helped characterize the clinical pathology, histopathology, and ultrastructural pathology associated with the disease.

Detecting Sulfamethazine Residues in Chicken Tissues Using the Delvotes® SP System.

Sulfamethazine-spiked chicken liver and kidney were tested for residues using the Delvotest SP. The results were compared to a standard plate assay using Bacillus subtilis as the test organism. The Delvotest SP gave positive responses to all homogenized liver replicates spiked with sulfamethazine at or above 1.0 µg/g of liver. Mixed responses were obtained at 0.5 µg/g and negative responses at ≤0.25 µg/g. The plate assay had a minimum sulfamethazine detection limit of 1 µg/g and 0.5 µg/g of liver and kidney, respectively. Chickens were dosed with sulfamethazine (100 mg/kg of body weight) daily for 5 days, and tissues were tested for residues after treatment stopped. The Delvotest SP was positive for all serum and kidney samples from the end of treatment to 24 h, and for muscle and liver samples up to 8 h. The plate assay detected the drug up to 24 h in serum and kidney samples and up to 8 h in liver and muscle samples. Kidney and serum samples both appeared to be good tissues for testing sulfamethazine residues in chickens. Serum could be used for antemortem screening, whereas kidney samples would appear to be the best for postmortem screening of residues in chickens.

Detecting Oxytetracycline Residues in Chicken Tissues Using the Delvotest® P System.

Oxytetracycline spiked chicken liver and kidney were tested for residues using Delvotest P and the results compared to standard plate assay using Bacillus cereus as test organism. Delvotest P detected all replicates at concentrations of ≥0.62 µg/g in liver and kidney. Between 0.41-0.2 µg/g, the responses were mixed (positive, doubtful, and negative); at 0.1 ≥ concentration, the responses were negative. The limit of detection of the plate assay was 0.2 and 0.31 µg/g for liver and kidney, respectively. Residue analysis on tissues from chickens dosed twice daily (for 4 d) with 25 mg/kg oxytetracycline was carried out using the Delvotest P and the plate assay. Delvotest P responses were all positive for 1-4 h after treatment in kidney and 1 and 2 h in liver and serum. Muscle never achieved concentrations that were consistently positive. The plate assay detected drug from 0.5-6 h in serum, from 0.5-8 h in liver and kidney, and at 4-6 h in muscle. Kidney tissue appeared to be the best for detecting oxytetracycline residues in chicken. The Delvotest P method was simpler to use and required less time; 3-4 h compared to about 18 h for the plate assay.