Non-Coding RNAs and SARS-Related Coronaviruses

The emergence of SARS-CoV-2 in 2019 has caused a major health and economic crisis around the globe. Gaining knowledge about its attributes and interactions with human host cells is crucial. Non-coding RNAs (ncRNAs) are involved in the host cells’ innate antiviral immune response. In RNA interference, microRNAs (miRNAs) may bind to complementary sequences of the viral RNA strand, forming an miRNA-induced silencing complex, which destroys the viral RNA, thereby inhibiting viral protein expression. There are several targets for human miRNAs on SARS-CoV-2’s RNA, most of which are in the 5’ and 3’ untranslated regions. Mutations of the viral genome causing the creation or loss of miRNA binding sites may have crucial effects on SARS-CoV-2 pathogenicity. In addition to mediating immunity, the ncRNA landscape of host cells further influences their susceptibility to virus infection, as certain miRNAs are essential in the regulation of cellular receptors that are necessary for virus invasion. Conversely, virus infection also changes the host ncRNA expression patterns, possibly augmenting conditions for viral replication and dissemination. Hence, ncRNAs typically upregulated in SARS-CoV-2 infection could be useful biomarkers for disease progression and severity. Understanding these mechanisms could provide further insight into the pathogenesis and possible treatment options against COVID-19.     

Is permanent congenital facial palsy caused by birth trauma?

OBJECTIVE: To study the relation between traumatic birth and the development of permanent facial palsy in the newborn. DESIGN: Retrospective case control study of children with 'congenital' facial palsy. SETTING: Two tertiary referral centres for patients with facial palsy. SUBJECTS: 61 children with established facial palsy. MAIN OUTCOME MEASURES: Odds ratios of recognised factors for birth injury: maternal primiparity, high birth weight, and the use of obstetric forceps at delivery. RESULTS: 13.2% of those studied had forceps assisted delivery compared to 10.2% in the normal population (odds ratio 1.34; 95% confidence intervals 0.61 to 2.97) 39.6% were born to primiparae compared to a national rate of 36.7% (1.13; 0.65 to 1.96) and only 18.9% weighed more than 3500 g at birth (0.37; 0.19 to 0.74). CONCLUSIONS: There is no association between the development of permanent 'congenital' facial palsy and recognised risk factors for birth injury. These data suggest an intrauterine rather than a traumatic aetiology.     

PHARMACOLOGICAL TREATMENT OF DIABETIC PERIPHERAL NEUROPATHY: CHALLENGES AND POSSIBILITIES

SUMMARY Peripheral neuropathy is a well-recognised late complication in both insulin-dependent and non-insulin-dependent diabetes. However, its exact cause remains unknown. Various pathogenic mechanisms have been proposed as an explanation for the development of nerve fibre damage and associated sensory loss in this disease. As a result, many kinds of drugs are currently under evaluation for the treatment of diabetic peripheral neuropathy. This paper describes the rationale behind the usage of all these drugs and reviews major clinical and preclinical results published so far. Supplementary intake of such natural, non-toxic compounds as vitamin constituents, linoleic acid and flavonoids is encouraged, as well as strict control of hyperglycaemia, until the efficacy of one or another experimental drug is established.     

Pharmacokinetics and dose linearity testing of methylprednisolone phosphate

The pharmacokinetics of methylprednisolone and methylprednisolone phosphate were investigated after intravenous administration of methylprednisolone phosphate to six healthy subjects at seven different doses between 16 and 1000 mg. Plasma, urine, and saliva were analyzed for methylprednisolone and methylprednisolone phosphate. Furthermore, endogenous hydrocortisone was measured in plasma. No non-linearity in the total body clearance of methylprednisolone phosphate or methylprednisolone could be detected. The average elimination half-life for the prodrug was 3.7 min indicating rapid hydrolysis. After 15 min more than 90 per cent of the phosphate has been hydrolyzed. No prodrug could be detected in saliva; very little of the ester (average 0.9 per cent of the dose) was excreted unchanged into the urine. Methylprednisolone is formed rapidly. The total body clearance was 21 1h-1, the terminal half-life 2.8 h. In the post-distribution phase methylprednisolone levels in saliva went parallel to plasma levels. The mean saliva/plasma ratio was 0.22. An average of 5.2 per cent of the dose was eliminated into the urine in the form of methylprednisolone. Hydrocortisone suppression was dose-dependent. For doses above 125 mg hydrocortisone levels were significantly lowered after 24 h. For doses above 500 mg the suppression was still significant after 48 h. The results indicate a rapid and predictable in vivo conversion of methylprednisolone phosphate to its active form methylprednisolone.     

Free colonic perforation without dilatation in ulcerative colitis

Free perforation occurred in only 7 of 702 patients with ulcerative colitis (1 percent) without toxic dilatation seen at The Mount Sinai Hospital from 1960 to 1981; however, these seven patients represented 30 percent (7 of 23) of all colonic perforations seen in patients with ulcerative colitis in our institution during the same period. Classic physical signs of peritonitis (silent, rigid abdomen and rebound tenderness) were absent in six of the seven patients, but all had a marked deterioration in general condition after perforation. Other signs included a sudden increase in severity of abdominal pain (three patients), marked abdominal distention (four patients), and a sharp decrease in frequency of bowel movements (six patients). Mortality was high (four of seven patients, 57 percent) and characterized by comparatively longer patient histories of colitis, longer current attacks, slightly greater delays between presumed perforation and operation, much higher transfusion requirements, and a 100 percent incidence of coagulopathy (thrombocytopenia and increased prothrombin time in three of four patients, and increased partial thromboplastin time in all four patients). The possibility of free perforation in ulcerative colitis must be considered in fulminating cases, even in the absence of colonic dilatation. Careful clinical monitoring and early surgical intervention may be the keys to reducing mortality.     

Comparison of sodium-meglumine ioxaglate and iopromide in coronary angiography

A clinical study was carried out in 20 patients in coronary angiography to compare two low-osmolar contrast media, sodium-meglumine ioxaglate and iopromide. Ten patients presented a stage III coronary disease and the other ten had a stage IV coronary disease. In the latter group, 70% of the patients received sodium-meglumine ioxaglate and 30% were given iopromide. None of the patients given iopromide had a previous history of allergic-like reactions to contrast media as opposed to the sodium-meglumine ioxaglate group where two patients had a previous hypersensitivity reaction to contrast agents. In spite of these adverse conditions in the sodium-meglumine ioxaglate group, no significant difference was found between both preparations as to overall tolerability. The following side effects were observed: slight nausea and wheezing in a patient given sodium-meglumine ioxaglate; medium intense nausea, vomiting and headache in a patient administered iopromide; one case of angina pectoris occurring 8 minutes post-injection of iopromide. Similarly, no significant difference in overall cardiac tolerability could be found between the two contrast media, although sodium-meglumine ioxaglate would tend to be better tolerated in terms of heart rate and contractility. Radiographic efficacy was considered to be equivalent for both contrast agents though the test solutions had different iodine concentrations. In summary, the two low osmolar contrast media proved well tolerated and showed satisfactory diagnostic efficacy in this population at high cardiovascular risk.