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Antiviral Effect of Hyperthermic Treatment in Rhinovirus Infection
Human rhinoviruses (HRV) are recognized as the major etiologic agents of the common cold. Starting from the observation that local hyperthermic treatment is beneficial in patients with natural and experimental common colds, we have studied the effect of brief hyperthermic treatment (HT) on HRV replication in HeLa cells. We report that a 20-min HT at 45°C is effective in suppressing HRV multiplication by more than 90% when applied at specific stages of the virus replication cycle. Synthesis of virus proteins is not affected by HT, indicating that the target for treatment is a posttranslational event. The antiviral effect is a transient cell-mediated event and is associated with the synthesis of the 70-kDa heat shock protein hsp70. Unlike poliovirus, rhinovirus infection does not inhibit the expression of hsp70 induced by heat. The possibility that hsp70 could play a role in the control of rhinovirus replication is suggested by the fact that a different class of HSP inducers, the cyclopentenone prostaglandins PGA1 and Δ12-PGJ2, were also effective in inhibiting HRV replication in HeLa cells. Inhibition of hsp70 expression by actinomycin D prevented the antiviral activity of prostaglandins in HRV-infected cells. These results indicate that the beneficial effect of respiratory hyperthermia may be mediated by the induction of a cytoprotective heat shock response in rhinovirus-infected cells.
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Hematologic differences between African-Americans and whites: the roles of iron deficiency and α-thalassemia on hemoglobin levels and mean corpuscular volume
The average results of some laboratory measurements, including the hemoglobin, mean corpuscular volume (MCV), serum transferrin saturation (TS), serum ferritin, and white blood cell count of African-Americans differ from those of whites. Anonymized samples and laboratory data from 1491 African-American and 31 005 white subjects, approximately equally divided between men and women, were analyzed. The hematocrit, hemoglobin, MCV, TS, and white blood cell counts of African-Americans were lower than those of whites; serum ferritin levels were higher. When iron-deficient patients were eliminated from consideration the differences in hematocrit, hemoglobin, and MCV among women were slightly less. The -3.7-kilobase α-thalassemia deletion accounted for about one third of the difference in the hemoglobin levels of African-Americans and whites and neither sickle trait nor elevated creatinine levels had an effect. Among all subjects, 19.8% of African-American women would have been classified as “anemic” compared with 5.3% of whites. Among men, the figures were 17.7% and 7.6%. Without iron-deficient or thalassemic subjects, the difference had narrowed to 6.1% and 2.77% and to 4.29% and 3.6%, respectively. Physicians need to take into account that the same reference standards for hemoglobin, hematocrit, MCV, and TS and the white blood cell count do not apply to all ethnic groups. (Blood. 2005;106:740-745)
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Evolution of the immune system in humans from infancy to old age
This article reviews the development of the immune response through neonatal, infant and adult life, including pregnancy, ending with the decline in old age. A picture emerges of a child born with an immature, innate and adaptive immune system, which matures and acquires memory as he or she grows. It then goes into decline in old age. These changes are considered alongside the risks of different types of infection, autoimmune disease and malignancy.
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Intrinsic Photosensitivity Enhances Motility of T Lymphocytes
Sunlight has important biological effects in human skin. Ultraviolet (UV) light striking the epidermis catalyzes the synthesis of Vitamin D and triggers melanin production. Although a causative element in skin cancers, sunlight is also associated with positive health outcomes including reduced incidences of autoimmune diseases and cancers. The mechanisms, however, by which light affects immune function remain unclear. Here we describe direct photon sensing in human and mouse T lymphocytes, a cell-type highly abundant in skin. Blue light irradiation at low doses (<300 mJ cm−2) triggers synthesis of hydrogen peroxide (H2O2) in T cells revealed by the genetically encoded reporter HyPerRed. In turn, H2O2 activates a Src kinase/phospholipase C-γ1 (PLC-γ1) signaling pathway and Ca2+ mobilization. Pharmacologic inhibition or genetic disruption of Lck kinase, PLC-γ1 or the T cell receptor complex inhibits light-evoked Ca2+ transients. Notably, both light and H2O2 enhance T-cell motility in a Lck-dependent manner. Thus, T lymphocytes possess intrinsic photosensitivity and this property may enhance their motility in skin.
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Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data.
Objectives To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect.Design Systematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials.Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015.Eligibility criteria for study selection Randomised, double blind, placebo controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration were eligible for inclusion if they had been approved by a research ethics committee and if data on incidence of acute respiratory tract infection were collected prospectively and prespecified as an efficacy outcome.Results 25 eligible randomised controlled trials (total 11 321 participants, aged 0 to 95 years) were identified. IPD were obtained for 10 933 (96.6%) participants. Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity <0.001). In subgroup analysis, protective effects were seen in those receiving daily or weekly vitamin D without additional bolus doses (adjusted odds ratio 0.81, 0.72 to 0.91) but not in those receiving one or more bolus doses (adjusted odds ratio 0.97, 0.86 to 1.10; P for interaction=0.05). Among those receiving daily or weekly vitamin D, protective effects were stronger in those with baseline 25-hydroxyvitamin D levels <25 nmol/L (adjusted odds ratio 0.30, 0.17 to 0.53) than in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (adjusted odds ratio 0.75, 0.60 to 0.95; P for interaction=0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted odds ratio 0.98, 0.80 to 1.20, P=0.83). The body of evidence contributing to these analyses was assessed as being of high quality.Conclusions Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit.
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Light as a Broad-Spectrum Antimicrobial
Antimicrobial resistance is a significant and growing concern. To continue to treat even simple infections, there is a pressing need for new alternative and complementary approaches to antimicrobial therapy. One possible addition to the current range of treatments is the use of narrow-wavelength light as an antimicrobial, which has been shown to eliminate a range of common pathogens. Much progress has already been made with blue light but the potential of other regions of the electromagnetic spectrum is largely unexplored. In order that the approach can be fully and most effectively realized, further research is also required into the effects of energy dose, the harmful and beneficial impacts of light on eukaryotic tissues, and the role of oxygen in eliciting microbial toxicity. These and other topics are discussed within this perspective.
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Low Serum Cholesterol Level Among Patients with COVID-19 Infection in Wenzhou, China
Background: A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel coronavirus COVID-19. Meanwhile, as the infection progressed, a large number of cases were also diagnosed in Wenzhou, China. The objective of the study is to describe the clinical laboratory features, especially lipid profile of the patients with COVID-19 infection in Wenzhou.
Methods: All cases were in a designated hospital in Wenzhou, and confirmed by positive virial nucleic acid detection through PCR assay. All clinical laboratory data were from the first test results after their admission. The unpaired t test was used for data analysis.
Findings: The absolute value of white blood cells, neutrophils and lymphocytes were lower than healthy controls ( P ＜0.05), more significantly, the patients had sharply decreased total cholesterol (TC), HDL-cholesterol and LDL-cholesterol levels ( P ＜0.001), 3.70±0.09mmol/L, 1.18±0.03 mmol/L and 1.82±0.08 mmol/L respectively, and increased monocyte/HDL-cholesterol ratio (0.37±0.02 vs 0.28±0.01 in healthy control). Among the patients, the primary infection cases showed the lower HDL-cholesterol levels (1.10±0.04 mmol/L) and higher monocyte/HDL-cholesterol ratio (0.43±0.03) than the secondary infection cases by person-to-person transmission ( P ＜0.05). Compared with the female patients, the male patients had higher levels of monocytes [(0.46±0.02) ×10 9 /L], M/HDL-C ratio (0.44±0.02), and lactate dehydrogenase (LDH, 257.6±12.32 U/l).
Interpretation: Low serum cholesterol level in the patients with COVID-19 in Wenzhou, China. Altered serum cholesterol provide important information, and is meaningful to understand the disease.
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An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice
Coronaviruses (CoVs) traffic frequently between species resulting in novel disease outbreaks, most recently exemplified by the newly emerged SARS-CoV-2, the causative agent of COVID-19. Here, we show that the ribonucleoside analog β-D-N4-hydroxycytidine (NHC; EIDD-1931) has broad-spectrum antiviral activity against SARS-CoV-2, MERS-CoV, SARS-CoV, and related zoonotic group 2b or 2c bat-CoVs, as well as increased potency against a CoV bearing resistance mutations to the nucleoside analog inhibitor remdesivir. In mice infected with SARS-CoV or MERS-CoV, both prophylactic and therapeutic administration of EIDD-2801, an orally bioavailable NHC prodrug (β-D-N4-hydroxycytidine-5′-isopropyl ester), improved pulmonary function and reduced virus titer and body weight loss. Decreased MERS-CoV yields in vitro and in vivo were associated with increased transition mutation frequency in viral, but not host cell RNA, supporting a mechanism of lethal mutagenesis in CoV. The potency of NHC/EIDD-2801 against multiple CoVs and oral bioavailability highlights its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic CoVs.
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Potential interventions for novel coronavirus in China: A systematic review
A review of vitamins, minerals, fats, drugs and Chinese medicines.
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There may be no immunity against Covid-19 - Only 4 per cent of 23,000 had antibodies
At least a quarter of the more than 23,000 samples tested could have been infected with the virus at some stage, according to the scientists. But only 4 per cent had developed antibodies as of April.
“People are unlikely to produce long-lasting protective antibodies against this virus,” the researchers concluded in a non-peer-reviewed paper posted on preprint website medRxiv.org on Tuesday.
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Individual and community-based measures to mitigate the spread of COVID-19 in Canada
"As COVID-19 continues to circulate in Canada and a significant proportion of the population is now vaccinated, different public health measures may be required."
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Allergy drug Singulair gets FDA's strongest warning over depression, suicide risk
The Food and Drug Administration is issuing a boxed warning — its strongest warning — for a widely prescribed asthma and allergy drug, citing its potential to cause "serious behavior and mood-related changes," the agency announced this week.
Montelukast, which is sold under the brand name Singulair and in generic form, may cause suicidal thoughts or actions, agitation, depression, sleeping problems and other mental health issues, the FDA said in a press release.
"Consistent with our prior evaluations, a wide variety of mental health side effects have been reported, including completed suicides," the FDA said.
Most reported cases of psychiatric side effects occurred during montelukast treatment, the FDA said, but some occurred after stopping.
The side effect rate is unknown, "but some reports are serious, and many patients and health care professionals are not fully aware of these risks," said Sally Seymour, director of the Division of Pulmonary, Allergy and Rheumatology Products in the FDA’s Center for Drug Evaluation and Research in a press release.
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