Search

The pathogenesis of COVID-19 is associated with a hyperinflammatory response; however, the precise mechanism of SARS-CoV-2-induced inflammation is poorly understood. Here, we investigated direct inflammatory functions of major structural proteins of SARS-CoV-2. We observed that spike (S) protein potently induced inflammatory cytokines and chemokines, including IL-6, IL-1β, TNFα, CXCL1, CXCL2, and CCL2, but not IFNs in human and mouse macrophages. No such inflammatory response was observed in response to membrane (M), envelope (E), and nucleocapsid (N) proteins. When stimulated with extracellular S protein, human and mouse lung epithelial cells also produced inflammatory cytokines and chemokines. Interestingly, epithelial cells expressing S protein intracellularly were non-inflammatory, but elicited an inflammatory response in macrophages when co-cultured. Biochemical studies revealed that S protein triggers inflammation via activation of the NF-κB pathway in a MyD88-dependent manner. Further, such an activation of the NF-κB pathway was abrogated in Tlr2-deficient macrophages. Consistently, administration of S protein-induced IL-6, TNF-α, and IL-1β in wild-type, but not Tlr2-deficient mice. Notably, upon recognition of S protein, TLR2 dimerizes with TLR1 or TLR6 to activate the NF-κB pathway. Taken together, these data reveal a mechanism for the cytokine storm during SARS-CoV-2 infection and suggest that TLR2 could be a potential therapeutic target for COVID-19.

The use of antimicrobial agents in food-producing animals has become an important public health issue due to the spread of microbial resistance. This study was aimed at identifying the antimicrobial agents available for poultry use and highlighting their possible impact on public health.Twenty-three randomly selected poultry farms and all veterinary pharmacies in the Eastern Province of Saudi Arabia were surveyed for the antibiotics used or dispensed. Further, a comprehensive literature survey was performed.Twenty-nine antimicrobial agents were identified as being available for poultry use, of which 22 (75.9%) were important for the treatment of human infections. Enrofloxacin, oxytetracycline, ampicillin, neomycin, sulphamethoxazole, colistin, doxycycline and erythromycin were the most frequently used drugs. Food-borne hypersensitivity reactions and the emergence of microbial resistance, as well as cross-resistance to the various groups of antibiotics in animals and its transfer to human pathogens, are well documented.The misuse of antibiotics in the local poultry industry poses a serious health risk to the public and may complicate the treatment of human infections. The veterinary use of antimicrobial agents, especially those with dual animal and human applications, should therefore be restricted. The establishment of a government department concerned with food and drug safety is also highly recommended.

The level of activity of the enzyme glucose-6-phosphate dehydrogenase (G6PD) was determined in 154 unrelated Saudi males and females with G6PD deficiency who were residing in the Eastern Province of Saudi Arabia. DNA was extracted from blood samples and analyzed for known G6PD mutations by polymerase chain reaction (PCR) and restriction fragment length polymorphism techniques. Two different polymorphic mutations were identified which accounted for 90% of the samples analyzed. Of 114 G6PD-deficient males, 96 had G6PD Mediterranean, nine had African deficient variant G6PD A- and in nine the mutation has not been identified. Of the 40 G6PD-deficient females, 34 were homozygous for the G6PD Mediterranean mutation and six were genetic compound, G6PD Mediterranean/G6PD A-. The data indicate that the G6PD Mediterranean mutation is the most common (84%) in the Eastern Province, followed by G6PD A- (5.8%). Seventy one subjects who suffered from favism were found to carry the Mediterranean mutation.

Samples of market-ready chicken muscle and liver from 32 local broiler farms were first screened for antibiotic residues by microbiological assay. The antibiotic-residue-positive muscles and livers from 22 farms were further analysed for norfloxacin (NFX) residues by high performance liquid chromatography. NFX was detected in 35.0% and 56.7% of raw antibiotic-residue-positive muscles and livers, respectively. The NFX-positive muscles and livers were respectively obtained from 11 (50.0%) and 14 (63.6%) of the 22 antibiotic-residue-positive farms. Since the maximum residue limit (MRL) for NFX has not yet been fixed, the MRL for enrofloxacin was used in the study. All NFX-positive farms had mean raw tissue levels, which were 2.7- to 34.3-fold higher than the MRL. Although cooking markedly reduced NFX tissue concentrations, mean detectable levels remained above MRL in large proportions of NFX-positive samples and farms. Susceptibility patterns of Enterobacteriaceae isolates from chicken and human patients to NFX showed alarmingly high rates of resistance in chicken isolates especially among Escherichia coli (45.9%) and Pseudomonas spp. (70.6%) compared with patients' isolates (10.5% and 18.2%, respectively). The study reveals widespread misuse of NFX in the local poultry industry, which may pose a major risk to public health including possible stimulation of bacterial resistance and hypersensitivity reactions to fluoroquinolones. More prudent use of fluoroquinolones in food-producing animals is therefore recommended. Further, there is a need to establish MRL values for NFX.

We have studied the pharmacokinetics of tenoxicam after single and multiple oral doses of 20 mg in five patients (2 men and 3 women) with end-stage renal disease undergoing haemodialysis. After a single dose, tenoxicam had a half-life (t1/2) of 33 h, an apparent clearance (CL.f-1) of 4.3 ml.min-1, and an apparent volume of distribution (Vz.f-1) of 11.81. The maximum tenoxicam concentration (Cmax) was 4.3 mg.l-1 at a median tmax of 1.7 h. There were no significant differences between the values calculated from the pre- or post-dialyser port plasma samples. Tenoxicam plasma concentrations measured during once daily dosing before and after haemodialysis showed that tenoxicam does not accumulate. Our findings suggest that dosage adjustment may not be required in patients with end-stage renal disease on haemodialysis taking tenoxicam.

Chicken muscle, liver and egg samples were collected from 33 broiler and 5 layer farms in the eastern province of Saudi Arabia over a period of two years starting from January 1996. Antibiotic-residue positive samples were identified in the products of 23 (69.7%) broiler and 3 (60%) layer poultry farms. 87% and 100.0% of the antibiotic-residue positive broiler farms were positive for at least one tetracycline compound in raw muscle and liver respectively, while 73.9% and 95.5% were positive for 2 or more tetracyclines in these two tissues, respectively. Furthermore, 82.6% and 95.5% of the antibiotic-residue-positive farms had mean concentrations of at least one tetracycline compound in excess of the permissible maximum residue limit (MRL) in raw muscle and liver, respectively. These compounds also remained chemically detectable after cooking. Tetracycline levels exceeded MRL in 14.4% of antibiotic-positive raw eggs but the overall mean tetracycline concentration in each farm was below MRL. This study confirmed widespread misuse of tetracycline agents including multiple use of drugs belonging to the same pharmacological group and lack of implementation of recommended withdrawal times. This may be contributing to the high resistance rates to tetracyclines in both chicken and human microbial isolates observed in the region. This study, therefore, stresses the need for stricter regulations for the use of antimicrobial drugs in the poultry industry as well as the inspection of chicken for drug residues prior to marketing.

The potential toxicity of Acacia nilotica was investigated in rats maintained on 2% and 8% acacia diet for 2 and 4 weeks. A significant reduction in body weight in all acacia-fed groups and a significant decrease in the levels of hemoglobin, serum total protein and total cholesterol in animals fed 8% acacia diet for up to 4 weeks were observed. These effects were, however, reversed one week after treatment termination. No significant changes in serum parameters of hepatic and renal functions, fasting glucose and triglycerides were observed. Further, no deaths among treated animals and no significant histopathological changes in liver sections were noted. It is concluded that A. nilotica, at 2% and 8% levels, has a low toxicity potential.

The aqueous extracts of Acacia nilotica and Hibiscus sabdariffa were tested for anti-inflammatory, analgesic and antipyretic activities in animal models. Acacia nilotica extract had an inhibitory effect on carrageenan induced paw edema and yeast-induced pyrexia in rats. It also produced a significant increase in the hot plate reaction time in mice. Hibiscus sabdariffa extract had no effect on paw edema but had an inhibitory effect on yeast induced pyrexia and a significant effect on the hot plate reaction time. Among the phytoconstituents found in both plants, flavanoids, polysaccharides and organic acids may be mainly responsible for their pharmacological activities.