Does Evidence Exist to Blunt Inflammatory Response by Nutraceutical Supplementation during COVID-19 Pandemic? An Overview of Systematic Reviews of Vitamin D,Vitamin C,Melatonin, and Zinc

More than one year has passed since the first cases of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome (SARS)-CoV-2 coronavirus were reported in Wuhan (China), rapidly evolving into a global pandemic. This infectious disease has become a major public health challenge in the world. Unfortunately, to date, no specific antivirals have been proven to be effective against COVID-19, and although a few vaccines are available, the mortality rate is not decreasing but is still increasing. One therapeutic strategy has been focused on infection prevention and control measures. In this regard, the use of nutraceutical supports may play a role against some aspect of the infection, particularly the inflammatory state and the immune system function of patients, thus representing a strategy to control the worst outcomes of this pandemic. For this reason, we performed an overview including meta-analyses and systematic reviews to assess the association among melatonin, vitamin C, vitamin D, zinc supplementation and inflammatory markers using three databases, namely, MEDLINE, PubMed Central and the Cochrane Library of Systematic Reviews. According to the evidence available, an intake of 50,000 IU/month of vitamin D showed efficacy in CRP. An amount of 1 to 2 g per day of vitamin C demonstrated efficacy both in CRP and endothelial function, and a dosage of melatonin ranging from 5 to 25 mg /day showed good evidence of efficacy in CRP, TNF and IL6. A dose of 50 mg/day of elemental zinc supplementation showed positive results in CRP. Based on the data reported in this review, the public health system could consider whether it is possible to supplement the current limited preventive measures through targeted nutraceutical large-scale administration.     

Social Distancing in Chronic Migraine during the COVID-19 Outbreak: Results from a Multicenter Observational Study

Background: The restrictions taken to control the rapid spread of COVID-19 resulted in a sudden, unprecedented change in people’s lifestyle, leading to negative consequences on general health. This study aimed to estimate the impact of such changes on migraine severity during 2020 March–May lockdown. Methods: Patients affected by migraine with or without aura, diagnosed by expert physicians, completed a detailed interview comprehensive of: assessment of migraine characteristics; measure of physical activity (PA) levels; measure of the intake frequency of main Italian foods; the Insomnia Severity Index (ISI) questionnaire investigating sleep disorders. Results: We included 261 patients with a mean age of 44.5 ± 12.3 years. During social distancing, 72 patients (28%) reported a headache worsening, 86 (33%) an improvement, and 103 (39%) a stable headache frequency. A significant decrease of the PA levels during COVID-19 quarantine in the whole study sample was observed (median total metabolic equivalent task (METs) decreased from 1170 to 510; p < 0.001). Additionally, a significant difference was reported on median ISI scores (from 7 to 8; p < 0.001), which were increased in patients who presented a stable or worsening headache. Conclusions: Our study confirmed that the restrictions taken during the pandemic have affected the practice of PA levels and sleep quality in migraine. Hence, PA and sleep quality should be assessed to find strategies for an improvement in quality of life.     

Carcinoma intraductal de próstata concomitante y respuesta al tratamiento hormonal en el carcinoma de próstata metastásico

Introduction and objectiveMost prostate cancers are classified as acinar adenocarcinoma. Intraductal carcinoma of the prostate (IDC-P) is a distinct histologic entity that is believed to represent retrograde spread of invasive acinar adenocarcinoma into prostatic ducts and acini.We have analyzed the impact of IDC-P in hormonal naïve and castration resistant metastatic prostate cancer patients.Patients and methodsWe retrospectively evaluated 118 metastatic castration resistant prostate cancer (mCRPC) patients who were initially diagnosed with distant metastases from May 2010 to September 2018. Group 1 patients included 81 metastatic PCa patients with acinar adenocarcinoma and Group 2 included 37 metastatic PCa patients with IDC-P.ResultsMean age at presentation was 76 years (IQR 73.4-78.7) in group 1 and 74 years (68.5-80.6) in group 2. Mean PSA at diagnosis was 619 ng/mL (IQR 85-1113) and 868 ng/mL (IQR 186-1922), respectively. Time to castration resistance was 24.7 months (IQR 16.7-32.7) in group 1 and 10.2 months (IQR 4.2-16.2) in group 2 (p = 0.007). Time to progression in CPRC patients was: 10.6 months (IQR 5.6-15.6) and at 6.2 months (3.2-9.2), respectively (p = 0.05). Overall survival was 57.9 months in group 1(CI 95% 56.4-59.5) and 38 months (CI 95% 19.9-48.06) in group 2 (p = 0.001). In the multivariate analysis, adenocarcinoma subtype was statistically significant p 0.014, CI 95% (HR 0.058, 0.006-0.56).ConclusionsIDC-P seems to be a subtype of prostate cancer that is associated with a shorter response to hormonal treatment when compared to acinar adenocarcinoma in metastatic patients. New drugs in CRPC scenario as abiraterone and enzalutamide also obtained less response in IDC-P patients. In daily clinical practice it might be interesting to take into account that patients with IDC-P may present shorter responses to first and second line hormonal treatments.     

Influence of the BDNF Val66Met polymorphism on weight loss after bariatric surgery: a 24-month follow-up

BackgroundBariatric surgery is currently the most effective long-term treatment for severe obesity. However, interindividual variation in surgery outcome has been observed, and research suggests a moderating effect of several factors including baseline co-morbidities (e.g., type 2 diabetes [T2D] and genetic factors). No data are currently available on the interaction between T2D and variants in brain derived neurotrophic factor (BDNF) and its effect on weight loss after surgery.ObjectivesTo examine the role of the BDNF Val66Met polymorphism (rs6265) and the influence of T2D and their interaction on weight loss after bariatric surgery in a cohort of patients with severe obesity.SettingUniversity hospital in Spain.MethodsThe present study evaluated a cohort of 158 patients with obesity submitted to bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy) followed up for 24 months (loss to follow-up: 0%). During the postoperative period, percentage of excess body mass index loss (%EBMIL), percentage of excess weight loss (%EWL), and total weight loss (%TWL) were evaluated.ResultsLongitudinal analyses showed a suggestive effect of BDNF genotype on the %EWL (P = .056) and indicated that individuals carrying the methionine (Met) allele may experience a better outcome after bariatric surgery than those with the valine/valine (Val/Val) genotype. We found a negative effect of a T2D diagnosis at baseline on %EBMIL (P = .004). Additionally, we found an interaction between BDNF genotype and T2D on %EWL and %EBMIL (P = .027 and P = .0004, respectively), whereby individuals with the Met allele without T2D displayed a greater %EWL and greater %EBMIL at 12 months and 24 months than their counterparts with T2D or patients with the Val/Val genotype with or without T2D.ConclusionOur data showed an association between the Met variant and greater weight loss after bariatric surgery in patients without T2D. The presence of T2D seems to counteract this positive effect.     

Hepatitis a virus identification in an outbreak by enzymatic amplification

From April 28th to May 22nd, 1987, the Medical Authority identified 13 cases (6 symptomatic cases) of hepatitis A (HA) in a school and in a college of Rome.The principal risk factor was determined to be full-time presence at the State school and boarders at the college. The distribution of HA cases suggested a person to person contact; antihepatitis A virus IgM were identified in 12 out of 13 cases with high levels of transaminases.During the disease epidemic, water samples were taken from the well of the college for bacteriological and virological analyses. The water was classified as undrinkable due to the presence of 16 total coliforms/100 ml and 35 total bacteria count at 36° C.Fecal coliforms, fecal streptococci and sulfite reducing clostridia were absent. Two water samples of 100 liters were collected and concentrated by adsorption-elution method on electropositive membranes or by ultrafiltration using a Millipore apparatus.Infectious Hepatitis A virus was only isolated from samples concentrated by adsorption-elution method on electropositive membranes using tissue culture methods and subsequently HA virus was identified by other traditional methods (Elisa and immunofluorescence). In contrast, PCR test performed on the concentrated samples, was positive only for the ultraconcentrated sample. The positivity of the PCR test confirmed the presence of the Hepatitis A virus in the well water.     

Immunohistochemical detection of p140trkA and p75LNGFR neurotrophin receptors in neuroblastoma

In neuroblastoma, high levels of mRNA for p14h ^trkA and p75 ^LNGFR neurotrophin receptors are predictive of favorable outcome. Their evaluation by Northern blot, however, requires substantial amounts of tissue and this prevents their routine evaluation as well as the possibility for multicenter studies to be easily carried out. In an attempt to overcome these limitations, the feasibility and reliability of determining both neurotrophin receptors on cryostat sections by immunohistochemistry were assessed, and these findings were compared to those obtained from Northern blot analysis. Primary tumor samples from 28 untreated patients at all stages were evaluated by using H10 anti-p140 ^trkA and ME20.4 anti-p75 ^LNGFR mAbs. Although weak, positiveimmunostaining was found in 9 of 28 tumors for p140 ^trkA and in 5 of 28 tumors for p75 ^LNGFR . As compared to Northern blot, the concordance rate was 79% (22 of 28 cases) for p140 ^trkA (p < 0.05) and 71% (20 of 28 cases) for p75 ^LNGFR (p < 0.05). No case negative for Northern blot was found to be positive with immunohistochemistry. Since only high mRNA levels for both receptors have been shown to be clinically relevant, their immunohistochemical detection, although less sensitive than Northern blot, can be just as sufficient and reliable as a prognostic tool, and possibly with a better cost-benefit ratio.     

Reduction of urinary 8-epi-prostaglandin F2α during cyclo-oxygenase inhibition in rats but not in man

1. 8-epi-prostaglandin (PG) F_2α, a major F₂ isoprostane, is produced in vivo by free radical-dependent peroxidation of lipid-esterified arachidonic acid. Both cyclo-oxygenase isoforms (COX-1 and COX-2) may also form free 8-epi-PGF_2α as a minor product. It has been recently seen in human volunteers that the overall basal formation of 8-epi-PGF_2α in vivo is mostly COX-independent and urinary 8-epi-PGF_2α is therefore an accurate marker of ‘basal'' oxidative stress in vivo.
2. To test the validity of this marker in the rat, we evaluated in vivo the effect of COX inhibition on the formation of 8-epi-PGF_2α vs prostanoids. Two structurally unrelated COX inhibitors (naproxen: 30 mg kg⁻¹ day⁻¹; indomethacin: 4 mg kg⁻¹ day⁻¹) were given i.p. to rats kept in metabolic cages. In vivo formation of 8-epi-PGF_2α was assessed by measuring its urinary excretion. Prostanoid biosynthesis was assessed by measuring urinary excretion of major metabolites of thromboxane (TX) and prostacyclin (2,3-dinor-TXB₁ and 2,3-dinor-6-keto-PGF_1α). All compounds were selectively measured by immunopurification/gas chromatography-mass spectrometry.
3. Naproxen reduced urinary excretion of 2,3-dinor-TXB₁ and 2,3-dinor-6-keto-PGF_1α but, unexpectedly, also that of 8-epi-PGF_2α (82, 49 and 52% inhibition, respectively). Indomethacin had a similar effect (77, 69 and 55% inhibition). Esterified 8-epi-PGF_2α in liver and plasma remained unchanged after indomethacin.
4. These findings prompted us to re-assess the contribution of COX activity to the systemic production of 8-epi-PGF_2α in man. We gave naproxen (1 g day⁻¹) to healthy subjects (four nonsmokers and four smokers). Urinary 8-epi-PGF_2α remained unchanged in the two groups (9.63±0.99 before vs 10.24±1.01 after and 20.14±3.00 vs 19.03±2.45 ng h⁻¹ 1.73 m⁻²), whereas there was a marked reduction of major urinary metabolites of thromboxane and prostacyclin (about 90% for both 11-dehydro-TXB₂ and 2,3-dinor-TXB₂; >50% for 2,3-dinor-6-keto-PGF_1α).
5. To investigate whether rat COX-1 produces 8-epi-PGF_2α more efficiently than human COX-1, we measured the ex vivo formation of 8-epi-PGF_2α and TXB₂ simultaneously in whole clotting blood. Serum levels of 8-epi-PGF_2α and TXB₂ were similar in rats and man.
6. We conclude that a significant amount of COX-dependent 8-epi-PGF_2α is present in rat but not in human urine under normal conditions. This implies that urinary 8-epi-PGF_2α cannot be used as an index of near-basal oxidant stress in rats. On the other hand, our data further confirm the validity of this marker in man.