Immunopharmacological perspective on zinc in SARS-CoV-2 infection.

The novel SARS-CoV-2 which was first reported in China is the cause of infection known as COVID-19. In comparison with other coronaviruses such as SARS-CoV and MERS, the mortality rate of SARS-CoV-2 is lower but the transmissibility is higher. Immune dysregulation is the most common feature of the immunopathogenesis of COVID-19 that leads to hyperinflammation. Micronutrients such as zinc are essential for normal immune function. According to the assessment of WHO, approximately one-third of the world's society suffer from zinc deficiency. Low plasma levels of zinc are associated with abnormal immune system functions such as impaired chemotaxis of polymorphonuclear cells (PMNs) and phagocytosis, dysregulated intracellular killing, overexpression of the inflammatory cytokines, lymphopenia, decreased antibody production, and sensitivity to microbes especially viral respiratory infections. Zinc exerts numerous direct and indirect effects against a wide variety of viral species particularly RNA viruses. The use of zinc and a combination of zinc-pyrithione at low concentrations impede SARS-CoV replication in vitro. Accordingly, zinc can inhibit the elongation step of RNA transcription. Furthermore, zinc might improve antiviral immunity by up-regulation of IFNα through JAK/STAT1 signaling pathway in leukocytes. On the other hand, zinc supplementation might ameliorate tissue damage caused by mechanical ventilation in critical COVID-19 patients. Finally, zinc might be used in combination with antiviral medications for the management of COVID-19 patients. In the current review article, we review and discuss the immunobiological roles and antiviral properties as well as the therapeutic application of zinc in SARS-CoV-2 and related coronaviruses infections.

Ameliorative effects of hydrogen sulfide (NaHS) on chronic kidney disease-induced brain dysfunction in rats: implication on role of nitric oxide (NO) signaling.

Chronic kidney disease (CKD) is a major public health problem worldwide and is associated with spatial learning deficits. The aim of the present study was to evaluate the protective effects of hydrogen sulfide (H2S) on CKD-mediated behavioral deficits with emphasis to the role of nitric oxide (NO) in these effects. Fifty rats were randomly allocated to five experimental groups including: sham, Five-sixth (5/6) nephrectomy (Nx), 5/6Nx + NaHS, 5/6Nx + NaHS+L-nitroarginine methyl ester (L-NAME), and 5/6Nx + NaHS+aminoguanidine (AMG). Twelve weeks after 5/6Nx, we evaluated proteinuria, creatinine clearance (CrCl), oxidative/antioxidant status, and hippocampus neuro-inflammation and NO synthase genes in all groups. Furthermore, training trials of all animals were conducted in the Morris water maze (MWM) task one day before animal euthanizing. As predicted, 5/6Nx induced several injuries, including enhancement of proteinuria and reduction of CCr, oxidant/antioxidant imbalance and up-regulation of TNF-α and IL-1ß gene expressions in the hippocampus tissues. As predicted, 5/6Nx resulted in learning and memory impairments, and increased escape latency during acquisition trials in the MWM task. Interestingly, NaHS (H2S donor) improved behavioral deficits, renal dysfunction, accelerated anti-oxidant/anti-inflammatory responses and increased eNOS and decreased iNOS. Moreover, these effects of NaHS were prevented by L-NAME but not AMG co-administration. In conclusion, H2S ameliorates CKD-mediated brain dysfunctions, through interaction with NO signaling in the hippocampus.

Correlation between clinical symptoms and peripheral immune response in HAM/TSP.

HTLV-1 infects principally CD4+ T cells that are the main reservoirs of the virus in vivo, which play an important role in the immunological response. Most of the infected patients are asymptomatic. However, 2-3% of patients will develop HAM/TSP or Adult T lymphoma. HAM/TSP is a chronic inflammatory disease of the central nervous system, which is characterized by unremitting myelopathic symptoms. Studies have shown that cytokines levels alterations (IFN-γ and TNF-α) were associated with tissue injury in HAM/TSP. The aims of this study were to compare the gene expression of IFN-γ, IL-4 and IL-10 of asymptomatic and HAM/TSP HTLV-1 infected patients, and to correlate the gene expression with those of clinical symptoms. 28 subjects were included, 20 asymptomatic HTLV-1 and 8 with HAM/TSP. Spasticity was evaluated using the Modified Ashworth Scale and the degree of walking aid was classified on a progressive scale. The relative gene expression of IFN-γ, IL-4, and IL-10 was measured by Real-Time PCR. Results showed high gene expression of IFN-γ for all patients, but it was higher among HAM/TSP. A significant correlation was observed between IFN-γ gene expression and the degree of walking aid, and IFN-γ gene expression was higher among wheelchair users compared to non-wheelchair users. No association was found with IL-4 and IL-10. These findings indicate that HAM/TSP patients express higher amounts of IFN-γ than asymptomatic patients, and more importantly, the expression of this cytokine was strongly correlated with the need of walking aid.

Association between histological findings, aminotransferase levels and viral genotype in chronic hepatitis C infection.

INTRODUCTION: The genomic heterogeneity of hepatitis C virus (HCV) influences liver disorders. This study aimed to determine the prevalence of HCV genotypes and to investigate the influence of these genotypes on disease progression. METHODS: Blood samples and liver biopsies were collected from HCV-seropositive patients for serological analysis, biochemical marker measurements, HCV genotyping and histopathological evaluation. RESULTS: Hepatitis C virus-ribonucleic acid (HCV-RNA) was detected in 107 patients (90.6% with genotype 1 and 9.4% with genotype 3). Patients infected with genotype 1 exhibited higher mean necroinflammatory activity and fibrosis. CONCLUSIONS: HCV genotype 1 was the most prevalent and was associated with greater liver dysfunction.

Association between histological findings, aminotransferase levels and viral genotype in chronic hepatitis C infection

Introduction: The genomic heterogeneity of hepatitis C virus (HCV) influences liver disorders. This study aimed to determine the prevalence of HCV genotypes and to investigate the influence of these genotypes on disease progression. Methods: Blood samples and liver biopsies were collected from HCV-seropositive patients for serological analysis, biochemical marker measurements, HCV genotyping and histopathological evaluation. Results: Hepatitis C virus-ribonucleic acid (HCV-RNA) was detected in 107 patients (90.6% with genotype 1 and 9.4% with genotype 3). Patients infected with genotype 1 exhibited higher mean necroinflammatory activity and fibrosis. Conclusions: HCV genotype 1 was the most prevalent and was associated with greater liver dysfunction. .

An orthopedic-, surgical-, and epidemiological-based investigation of leprosy, in the Tamil Nadu state of India.

No other research paper has ever been written about leprosy in this manner. The orthopedic and surgical implications, as well as the functional debility caused by the disease, have not been previously explained by past research as they have in such a comprehensive manner in this paper. The results of this study have regional and global implications as they pertain to disease pathology, risk factor recognition/disease prevention, and treatment. This paper is a unique, in that it also serves as a combination of a review of the current medical literature, as well as an epidemiological survey of the disease in a region of the world which has never been researched in the past. Clinical data points to the possibility of a new strain of the disease. This information is of significance because it effects prevention and improved treatment of the disease, which leads to devastating sequela. This was a cross-sectional study involving subjects diagnosed with leprosy in the Chengalpet region of the Kancheepuram District, of the Tamil Nadu state of India. The study was performed at the Tamil Nadu Medical College Teaching Hospital and Research Center. This study included various physical examinations, observation and survey of lesions, questionnaires in regard the debilitating orthopedic and medical effects of the disease, as well as treatment options.

Recurrence of Helicobacter pylori infection 1 year after successful eradication: a prospective study in Northern Iran.

BACKGROUND: The aim was to investigate the H. pylori recurrence rate one year after successful eradication in dyspeptic patients in Guilan province, northern Iran. MATERIAL/METHODS: Patients with chronic dyspepsia were enrolled in our gastroenterology clinic. Gastric biopsies were obtained by endoscopy and H. pylori infection was diagnosed using the Rapid Urease Test (RUT). Patients with H. pylori infection were prescribed clarithromycine-based quadruple therapy for 10 days. The (13)C urea breath test ((13)C-UBT) was used to assess H. pylori status 10 weeks after completing H. pylori therapy. Patients who H. pylori-negative had a second (13)C-UBT after 1 year to establish the recurrence rate. RESULTS: Of 269 dyspeptic patients with RUT positivity for H. pylori in endoscopy who were treated with the quadruple regimen for 10 days, 240 had negative (13)C-UBT 10 weeks after the end of therapy, with an eradication rate of 89.2% (95%CI: 82.2-97.2%) by per-protocol analysis. Of this group, 153 patients (63.8%) were female. The (13)C-UBT at 1 year was positive in 12 (5.0%) of the 240 patients. A mean age of >35 year, being female, living in an urban area, and a household size of more than 5 person were more frequent in the (13)C-UBT-positive patients at 1 year, but they were not statistically significant. In this study there was also no significant relationship between, job, educational status, and the source of domestic water with recurrence of H. pylori infection. CONCLUSIONS: According to these data, the H. pylori recurrence rate in our region is 5% after successful eradication.

Illusory spectrotemporal ripples created with binaurally correlated noise.

Binaural disparities are the primary acoustic cues employed in sound localization tasks. However, the degree of binaural correlation in a sound serves as a complementary cue for detecting competing sound sources [J. F. Culling, H. S. Colburn, and M. Spurchise, "Interaural correlation sensitivity," J. Acoust. Soc. Am. 110(2), 1020-1029 (2001) and L. R. Bernstein and C. Trahiotis, "On the use of the normalized correlation as an index of interaural envelope correlation," J. Acoust. Soc. Am. 100, 1754-1763 (1996)]. Here a random chord stereogram (RCS) sound is developed that produces a salient pop-out illusion of a slowly varying ripple sound [T. Chi et al., "Spectro-temporal modulation transfer functions and speech intelligibility," J. Acoust. Soc. Am. 106(5), 2719-2732 (1999)], even though the left and right ear sounds alone consist of noise-like random modulations. The quality and resolution of this percept is systematically controlled by adjusting the spectrotemporal correlation pattern between the left and right sounds. The prominence and limited time-frequency resolution for resolving the RCS suggests that envelope correlations are a dominant binaural cue for grouping acoustic objects.

The contribution of spike threshold to acoustic feature selectivity, spike information content, and information throughput.

Hypotheses of sensory coding range from the notion of nonlinear "feature detectors" to linear rate coding strategies. Here, we report that auditory neurons exhibit a novel trade-off in the relationship between sound selectivity and the information that can be communicated to a postsynaptic cell. Recordings from the cat inferior colliculus show that neurons with the lowest spike rates reliably signal the occurrence of stereotyped stimulus features, whereas those with high response rates exhibit lower selectivity. The highest information conveyed by individual action potentials comes from neurons with low spike rate and high selectivity. Surprisingly, spike information is inversely related to spike rates, following a trend similar to that of feature selectivity. Information per time interval, however, was proportional to measured spike rates. A neuronal model based on the spike threshold of the synaptic drive accurately accounts for this trade-off: higher thresholds enhance the spiking fidelity at the expense of limiting the total communicated information. Such a constraint on the specificity and throughput creates a continuum in the neural code with two extreme forms of information transfer that likely serve complementary roles in the representation of the auditory environment.

Leukemia markers expression of peripheral blood vs bone marrow blasts using flow cytometry.

BACKGROUND: Flow cytometric techniques are widely used in clinical hematology. Characterization of leukemias by immunotyping is particularly helpful when the morphology is difficult to interpret. The major advantage of using immune markers by flow cytometry is the identification of particular leukemia subtype, not recognized by morphologic criteria, which may have prognostic significance. Current literature suggests when peripheral blood (PB) is consisted of 30% blasts or higher diagnosis of acute leukemia is most likely. However, bone marrow aspiration may also be performed as a confirmatory diagnosis. Immunotyping of PB and BM in leukemias not only determine the decision making for a specific therapeutic regimen, but also is a practical prognostic indicator. MATERIAL/METHODS: We evaluated 18 patients with acute myeloid Leukemia (AML) and 13 patients with acute lymphoid leukemia (ALL). In all cases, the amount of blasts in PB was 30% or higher. Two ml PB and BM samples from each patient was collected. Following the preparation process, expression of markers was detected by using flow cytometry. The panel of monoclonal antibodies used in this study were consisted of CD3, CD7, CD5 (for T lymphocytes lineage); CD19, CD22, CD20, CD10 (for B lymphocytes lineage); CD13, CD14, CD33 (for myeloid subsets); and TDT, HLA-DR, CD45 (non lineage restricted). Expression levels of PB and BM markers were compared by using statistical analysis. RESULTS: The results showed apparent discrepancies for some markers in ALL group. However, in AML patients most of the selected markers have shown considerable correlation between PB and BM samples. Only four markers (CD13, CD14, CD45, and HLA-DR) showed positive correlation. In contrast, most markers (CD3, CD5, CD13, CD14, CD19, CD45, HLA-DR, and TdT) showed strong correlation between PB and BM samples in AML group. CONCLUSIONS: The findings of this study suggests that targeted gating strategy for blast population as well as selection of a suitable panel of monoclonal antibodies may be essential for diagnosis of leukemia resulting in similar immunotyping pattern in PB and BM. Although our results are preliminary, this can minimize the necessity of BM aspiration for leukemia patients.

Severe acute respiratory syndrome.

The mysterious severe acute respiratory syndrome (SARS) that has originated from the southern Chinese province of Guangdong appears to be a major public health threat and medical challenge. Laboratory studies of SARS patients in a number of countries identified the etiologic agent being a novel member of coronaviridae. High RNA concentrations of this virus in sputum make it as a highly infectious agent. Low concentrations of viral genome are also detectable in feces. Coronaviruses are ubiquitos. They cause disease in many animals including pigs, cattle, dogs, cats, and chickens. These viruses have been associated with upper respiratory infections and sometimes pneumonia in humans. SARS presents with fever, cough, malaise, dyspnea, and hypoxemia. Chest radiographs from affected regions are associated with progressive airway disease. Clinical laboratory features of SARS include lymphopenia, thrombocytopenia, and elevated lactate dehydrogenase levels. Currently, there is no FDA approved pharmacologic treatment for SARS. To date, no convincing clinical data is available for treatment of SARS with ribavirin. While there are some controversies about the use of systemic corticosteroids, Martin et al, in this issue of MSM, present their views on the use of pentoxyfylline (PTX) as a potential agent to be considered for SARS treatment. Finally, our analytical approach to the risks of SARS will certainly enable us to

Prevalence of hepatitis B and C seromarkers and abnormal liver function tests among hemophiliacs in Guilan (northern province of Iran).

BACKGROUND: The aim of this study was to determine the seroprevalence of hepatitis B and C viruses and abnormal liver function tests among hemophiliacs in Guilan province, Iran. MATERIAL/METHODS: Patients registered with Guilan Hemophilia Society (GHS) were enrolled in this study, and evaluated for the presence of hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV-Ab) and liver function tests. RESULTS: One hundred and one patients (100 males, 1 female, mean age 19.7 years, range 3-71 years) from 110 registered hemophiliacs were enrolled in this study. 29 patients (28.7%) had elevated Alanine aminotransferase (ALT), 27 (26.7%) and 72 (71.3%) were positive for HBsAg and HCV-Ab, respectively. Seropositivity for HCV-Ab correlated with the duration of treatment with clotting factor until 1997 (P=0.01). There was also an inverse correlation between factor VIII & IX activity and seropositivity for HCV-Ab (P<0.001) and HBsAg (P<0.04). HCV-Ab was more likely to be positive among those received lyophilized factor VIII and cryoprecipitate than lyophilized factor VIII alone (P<0.01). In addition HCV-Ab seropositivity was more common among those received factor IX concentrate and fresh frozen plasma (FFP) than those received only FFP (P<0.01). CONCLUSIONS: Based upon our finding, prevalence of HBsAg positive cases in Guilan province was higher than other studies. Although frequency of HCV-Ab was similar to other studies, frequency of increased ALT was less. Upon the results emerged from this study, we recommend that all hemophiliacs should be vaccinated against HBV and should have regular program for checking HCV.