The role of vitamin C in pneumonia and COVID-19 infection in adults with European ancestry: a Mendelian randomisation study.

BACKGROUND: High dose vitamin C infusion has been proposed to treat critically ill patients, including patients with pneumonia and severe COVID-19. However, trials have shown mixed findings. Here we assessed the unconfounded associations of vitamin C with COVID-19 and pneumonia using the Mendelian randomisation approach. METHODS: This is a separate-sample Mendelian randomisation study using publicly available data. We applied single nucleotide polymorphisms (SNPs) that were associated with plasma vitamin C, in a recent genome-wide association study (GWAS) as genetic instruments to the GWAS of severe COVID-19, COVID-19 hospitalisation and any infection in the COVID-19 host genetics initiative and the GWAS of pneumonia in the UK Biobank, to assess whether people with genetically predicted higher levels of plasma vitamin C had lower risk of severe COVID-19 and pneumonia. RESULTS: Genetically predicted circulating levels of vitamin C was not associated with susceptibility to severe COVID-19, COVID-19 hospitalisation, any COVID-19 infection nor pneumonia. Similar results were obtained when a weighted median and MR-Egger methods were used. CONCLUSIONS: Mendelian randomisation analysis provided little evidence for an association of genetically predicted circulating levels of vitamin C with COVID-19 or pneumonia and thus our findings provided little support to the use of vitamin C in prevention and treatment in these patients, unless high dose vitamin C infusion has therapeutic effects via different biological pathways.

Disconnect Between Genes Associated With Ischemic Heart Disease and Targets of Ischemic Heart Disease Treatments.

BACKGROUND: Development of pharmacological treatments to mitigate ischemic heart disease (IHD) has encompassed disappointing results and expensive failures, which has discouraged investment in new approaches to prevention and control. New treatments are most likely to be successful if they act on genetically validated targets. We assessed whether existing pharmacological treatments for IHD reduction are acting on genetically validated targets and whether all such targets for IHD are currently being exploited. METHODS: Genes associated with IHD were obtained from the loci of single nucleotide polymorphisms reported in either of two recent genome wide association studies supplemented by a gene-based analysis (accounting for linkage disequilibrium) of CARDIoGRAMplusC4D 1000 Genomes, a large IHD case (n=60,801)-control (n=123,504) study. Treatments targeting the products of these IHD genes and genes with products targeted by current IHD treatments were obtained from Kyoto Encyclopedia of Genes and Genomes and Drugbank. Cohen's kappa was used to assess agreement. RESULTS: We identified 173 autosomal genes associated with IHD and 236 autosomal genes with products targeted by current IHD treatments, only 8 genes (PCSK9, EDNRA, PLG, LPL, CXCL12, LRP1, CETP and ADORA2A) overlapped, i.e. were both associated with IHD and had products targeted by current IHD treatments. The Cohen's kappa was 0.03. Interventions related to another 29 IHD genes exist, including dietary factors, environmental exposures and existing treatments for other indications. CONCLUSIONS: Closer alignment of IHD treatments with genetically validated physiological targets may represent a major opportunity for combating a leading cause of global morbidity and mortality through repurposing existing interventions.

Effects of dietary selenium deficiency on mRNA levels of twenty-one selenoprotein genes in the liver of layer chicken.

Selenium (Se) is an essential trace element in many life forms due to its occurrence as selenocysteine (Sec) residue in selenoproteins. However, little is known about the expression pattern of selenoproteins in the liver of layer chicken. To investigate the effects of Se deficiency on the mRNA expressions of selenoproteins in the liver tissue of layer chickens, 1-day-old layer chickens were randomly allocated into two groups (n=120/group). The Se-deficient group (-Se) was fed a Se-deficient corn-soy basal diet; the Se-adequate group as control (+Se) was fed the same basal diet supplemented with Se at 0.15 mg/kg (sodium selenite). The liver tissue was collected and examined for mRNA levels of 21 selenoprotein genes at 15, 25, 35, 45, 55, and 65 days old. The data indicated that the mRNA expressions of Gpx1, Gpx2, Gpx3, Gpx4, Sepn1, Sepp1, Selo, Sepx1, Selu, Txnrd1, Txnrd2, Txnrd3, Dio1, Dio2, SPS2, Selm, SelPb, Sep15, and Sels were decreased (p<0.05), but not the levels of Dio3 and Seli (p>0.05). The results showed that the mRNA levels of 19 selenoprotein (except Seli and Dio3) genes in the layer chicken liver were regulated by diet Se level. The present study provided some compensated data about the roles of Se in the regulation of selenoproteins.

[Changes and its measurement of intracellular Ca2+ during exposure to hyperbaric oxygen].

Objective. To investigate the rule of change of intracellular Ca2+ and its measurement method during exposure to hyperbaric oxygen (HBO). Method. Microfluorescence method was used to measure the changes of intracellular Ca2+ concentration in co-cultured endothelial cells (EC) and smooth muscle cells (SMC) in a specially designed miniature oxygen chamber. Result. (1) [Ca2+]i changes during HBO exposure can be clearly observed directly in the chamber. (2) Within 5 min during 0.2 MPa and 0.3 MPa HBO exposure, EC[Ca2+]i and SMC[Ca2+]i showed a tendency, to increase at first and then decrease with time throughout the exposures, especially the SMC[Ca2+]i. The EC ruptured under exposure to 0.4 MPa HBO. Conclusion. During HBO exposure, EC[Ca2+]i and SMC[Ca2+]i showed biphasic changes, which increased at first and then decreased. The technique and method used were reliable and suitable for investigating of intracellular [Ca2+]i changes under HBO.

New secoiridoid glucosides from Jasminum lanceolarium.

Two new secoiridoid glucosides, the trans-P-coumaroyl and trans-feruloyl esters of 10-hydroxyoleoside, jaslanceosides A (2) and B (3), were isolated from the leaves and stems of Jasminum lanceolarium (Oleaceae) in addition to jasminoside (1) and 10-hydroxyoleoside dimethyl ester (8). The structures of these compounds have been elucidated on the basis of spectral and chemical methods.

Pneumatic reduction of intussusception in children.

Over the past decade, pneumatic reduction has been increasingly accepted as the treatment of choice for pediatric intussusception. However the effectiveness of air compared with the more traditional barium reduction of intussusception continues to be a source of concern and debate. From August 1993 to November 1994, pneumatic reduction was used to treat 75 episodes in 73 patients with proven intussusception at Chang Gung Memorial Hospital, Taoyuan. Two patients underwent air reduction twice because of recurrence following an initial successful reduction. The recurrence rate was 3%. Successful reduction was achieved in 65/75 (87%) episodes. None of the patients experienced any complications following the procedure. In two of the 10 patients in whom reduction failed, one was subsequently found to have a Meckel's diverticulum and the other a duplication cyst as a leading point. This prospective study indicates that air enema is a safe and effective form of treatment for intussusception in infants and children. Pneumatic reduction should be the treatment of choice in the initial management of intussusception.

Effects of copper concentration on mineral nutrient uptake and copper accumulation in protein of copper-tolerant and nontolerant Lotus purshianus L.

One copper-tolerant and one copper-sensitive inbred line of Lotus purshianus L. derived from a copper mine waste site in Northern California and one inbred line of the same species derived from a pasture next to the mine waste were examined for the effects of excessive copper concentrations on mineral nutrient uptake and accumulation of copper in protein fractions. Plants were grown from seeds for a period of 24 days in a modified Hoagland nutrient solution culture supplemented with 3, 6, and 10 microM copper as copper sulfate. The basal nutrient solution without copper amendment was used as the control treatment. The uptake of Cu found in the roots was 100 times or more than that in the leaves. The root tissue copper concentrations reached a plateau under 6 microM copper treatment. The leaf tissue copper concentrations increased with the increase of copper concentration in the solution culture. No difference in pattern of copper uptake was detected between the copper-tolerant and nontolerant plants. The effects of excessive copper concentrations caused reduction of Ca uptake in the leaf tissue and P uptake in both the root and leaf tissues, and no difference was found between the copper-tolerant and nontolerant plants. Increased tissue copper concentration caused greater reduction of Fe, Mn, and Zn uptake in the nontolerant plants than in the tolerant plants; this difference may be important for the growth of the tolerant plants under conditions of excessive copper concentrations. Protein extracted from the roots and leaves of both the copper tolerant and nontolerant plants was subjected to Sephadex G-75 column separation. Two major peaks of protein fractions were detected. Under low (normal level) copper concentration treatment, the copper-tolerant and nontolerant plants had similar Cu/protein ratios. However, under high copper concentration challenged conditions the copper-tolerant plant had a considerably greater Cu/protein ratio (peak II protein) than the nontolerant plants. The amino acid composition of the copper-rich protein fraction (peak II) extracted from both the tolerant and nontolerant plants demonstrated a high asparate (about 25%) content. The contents of glutamate, cystine, and glycine were about 11, 2.5, and 10%, respectively, and the rest of the amino acids were in a range of 2 to 6%. This pattern of amino acid composition is different from the amino acid composition of the phytochelatin metallothionein-like proteins found in copper-tolerant plants which are very high in cysteine.(ABSTRACT TRUNCATED AT 400 WORDS)

Left ventricular opacification after peripheral venous injection of a modified albumin solution.

The usefulness of a modified albumin solution was assessed in 8 dogs after peripheral venous and inferior vena cava injections. The contrast agent is a mixed solution made of glucose, albumin and glycerin, with sonicated microbubble diameter of 5.0 +/- 2.3 microns. Multiple injections (8 ml each) of this contrast agent (total 80 injections) into peripheral vein and inferior cava were performed. The blood pressure from femoral artery was measured before, during and after injections. Two-dimensional echocardiograms were recorded in a modified long axis view on videotapes for play back analysis. The pulmonary transit time and left ventricular contrast persistent time was determined for each injection. The videodensity of the region of interest (ROI) at the center of right ventricle and left ventricle was measured. The background videodensity of both ventricles was evaluated. The videodensity over the ROI of both ventricles with peak contrast enhancement was measured in all frames for 3 consecutive cardiac cycles. The peak videodensity of right and left ventricle subtracting the background videodensity of each ventricles was further calculated respectively. The injections caused no change in blood pressure or heart rate. All injections produced right ventricular contrast echo. As much as 85% of peripheral venous and 82.5% of inferior vena cava injections resulted in left ventricular contrast which was 0.68 and 0.65 as bright as that produced in the right ventricle. Pulmonary transit time and left ventricle contrast persistent time of peripheral venous injection was 4.05 +/- 0.53 and 13.67 +/- 4.28 seconds respectively. No difference of these data (3.93 +/- 0.47 and 11.65 +/- 4.66 seconds) from those produced by inferior vena cava injections were noted.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effect of trace elements in traditional Chinese medicine in the light of Chinese medicinal theory].

This paper presents a survey of the study on the relationship between trace elements and effect of treatment in traditional Chinese medicine. The authors have made a review in the light of Chinese medicinal theory.

[Determination of berberine in Angong Niuhuang Wan by HPLC].

A normal phase liquid chromatographic method was developed for the determination of berberine-type alkaloids in rhizoma Coptidis and traditional Chinese medicine--Angong Niuhuang Wan. Experimental evidences indicate that a normal phase system of a silica column (3.9 x 250 mm) as stationary phase with an eluent of ethyl acetate-formic acid-ethanol (15:3:2) as mobile phase can separate excellently (R5 greater than 1.5) four berberine-type alkaloids in the samples tested. According to the results obtained with this method the percent content of berberine hydrochloride in some Angong Niuhuang Wan from different factories and different batches was 0.331-0.456% and the average recovery was 97.23%; coefficient of variation was 1.2%.

[Determination of berberine and palmatine in cortex phellodendron and Chinese patent medicines by HPLC].

Berberine (1) and palmatine (2) in cortex phellodendron and Chinese patent medicines were determined by HPLC. The optimal composition of mobile phase CH3COOEt-HCOOH-EtOH (15:3:2) for HPLC separation of berberine and palmatine was successfully determined by using window diagram technique. Detection wavelength was 346nm. Flow rate: 1.5 ml/min. Calibration graphs for 1 and 2 were rectilinear for 0.06-0.32 micrograms and 0.12-0.32 micrograms respectively. The average recoveries of the two corresponding components were found to be over 96% and their coefficients of variation were below 5%.