Antiviral activity of zinc against hepatitis viruses: current status and future prospects.

Viral hepatitis is a major public health concern globally. World health organization aims at eliminating viral hepatitis as a public health threat by 2030. Among the hepatitis causing viruses, hepatitis B and C are primarily transmitted via contaminated blood. Hepatitis A and E, which gets transmitted primarily via the feco-oral route, are the leading cause of acute viral hepatitis. Although vaccines are available against some of these viruses, new cases continue to be reported. There is an urgent need to devise a potent yet economical antiviral strategy against the hepatitis-causing viruses (denoted as hepatitis viruses) for achieving global elimination of viral hepatitis. Although zinc was known to mankind for a long time (since before Christ era), it was identified as an element in 1746 and its importance for human health was discovered in 1963 by the pioneering work of Dr. Ananda S. Prasad. A series of follow up studies involving zinc supplementation as a therapy demonstrated zinc as an essential element for humans, leading to establishment of a recommended dietary allowance (RDA) of 15 milligram zinc [United States RDA for zinc]. Being an essential component of many cellular enzymes and transcription factors, zinc is vital for growth and homeostasis of most living organisms, including human. Importantly, several studies indicate potent antiviral activity of zinc. Multiple studies have demonstrated antiviral activity of zinc against viruses that cause hepatitis. This article provides a comprehensive overview of the findings on antiviral activity of zinc against hepatitis viruses, discusses the mechanisms underlying the antiviral properties of zinc and summarizes the prospects of harnessing the therapeutic benefit of zinc supplementation therapy in reducing the disease burden due to viral hepatitis.

Plateau Iris: A Review.

Purpose: To review the concept of plateau iris and summarize the recent evidence on its diagnosis and management. Methods: This is a narrative review on the plateau iris. A literature review was conducted in PubMed, Google Scholar, and Scopus databases using keywords: angle-closure glaucoma, glaucoma, nonpupillary block glaucoma, plateau iris, and plateau iris management. Results: This review defined the current knowledge about plateau iris. First of all, the anatomy and epidemiology were discussed. Then, we outlined the available evidence on the diagnosis of plateau iris and its differential diagnosis. Conclusively, the treatment options were mentioned. Conclusions: Plateau iris is a condition in which nonpupillary block mechanisms are responsible for intraocular pressure elevation and angle closure attack when a patent peripheral iridotomy has removed the relative pupillary block. An anteriorly positioned ciliary body causes mechanical obstruction of trabecular meshwork in these patients. It is usually seen in younger patients with angle closure and is diagnosed by gonioscopic examination and imaging modalities such as Ultrasound biomicroscopy. Despite the known mechanism of plateau iris, there is no consensus over treatment. Low-dose pilocarpine and Argon laser peripheral iridoplasty are nonsurgical treatments for these patients, but their effects are short-term. Cataract extraction with/without endocyclophotocoagulation (ECP), endocycloplasty, excisional goniotomy, and transscleral cyclophotocoagulation are alternative treatments. Patients should be examined periodically for further progression or recurrence of plateau iris. In cases of glaucoma unresponsive to conventional medical treatments, surgical treatments such as trabeculectomy and drainage devices should be considered.

Potential antiviral activities of chrysin against hepatitis B virus.

BACKGROUND: Interferon and nucleos(t)ide analogues are current therapeutic treatments for chronic Hepatitis B virus (HBV) infection with the limitations of a functional cure. Chrysin (5, 7-dihydroxyflavone) is a natural flavonoid, known for its antiviral and hepatoprotective activities. However, its anti-HBV activity is unexplored. METHODS: In the present study, the anti-hepatitis B activity of chrysin was investigated using the in vitro experimental cell culture model, HepG2 cells. In silico studies were performed where chrysin and lamivudine (used here as a positive control) were docked with high mobility group box 1 protein (HMGB1). For the in vitro studies, wild type HBV genome construct (pHBV 1.3X) was transiently transfected in HepG2. In culture supernatant samples, HBV surface antigen (HBsAg) and Hepatitis B e antigen (HBeAg) were measured by enzyme-linked immunosorbent assay (ELISA). Secreted HBV DNA and intracellular covalently closed circular DNA (cccDNA) were measured by SYBR green real-time PCR. The 3D crystal structure of HMGB1 (1AAB) protein was developed and docked with the chrysin and lamivudine. In silico drug-likeness, Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) properties of finest ligands were performed by using SwissADME and admetSAR web servers. RESULTS: Data showed that chrysin significantly decreases HBeAg, HBsAg secretion, supernatant HBV DNA and cccDNA, in a dose dependent manner. The docking studies demonstrated HMGB1 as an important target for chrysin as compared to lamivudine. Chrysin revealed high binding affinity and formed a firm kissing complex with HMGB1 (∆G = - 5.7 kcal/mol), as compared to lamivudine (∆G = - 4.3 kcal/mol), which might be responsible for its antiviral activity. CONCLUSIONS: The outcome of our study establishes chrysin as a new antiviral against HBV infection. However, using chrysin to treat chronic HBV disease needs further endorsement and optimization by in vivo studies in animal models.

Antiviral Activity of Zinc Oxide Nanoparticles and Tetrapods Against the Hepatitis E and Hepatitis C Viruses.

Hepatitis E virus (HEV) causes an acute, self-limiting hepatitis. The disease takes a severe form in pregnant women, leading to around 30% mortality. Zinc is an essential micronutrient that plays a crucial role in multiple cellular processes. Our earlier findings demonstrated the antiviral activity of zinc salts against HEV infection. Zinc oxide (ZnO) and its nanostructures have attracted marked interest due to their unique characteristics. Here we synthesized ZnO nanoparticles [ZnO(NP)] and tetrapod-shaped ZnO nanoparticles [ZnO(TP)] and evaluated their antiviral activity. Both ZnO(NP) and ZnO(TP) displayed potent antiviral activity against hepatitis E and hepatitis C viruses, with the latter being more effective. Measurement of cell viability and intracellular reactive oxygen species levels revealed that both ZnO(NP) and ZnO(TP) are noncytotoxic to the cells even at significantly higher doses, compared to a conventional zinc salt (ZnSO4). Our study paves the way for evaluation of the potential therapeutic benefit of ZnO(TP) against HEV and HCV.

Accelerated Corneal Collagen Cross-Linking in Pediatric Keratoconus.

PURPOSE: To evaluate the visual, refractive, and topographic outcomes of accelerated corneal collagen cross-linking (CXL) in the pediatric age group. METHODS: In this retrospective case series study, 89 eyes of 56 patients with progressive keratoconus (KCN) who were under or equal to 18 years old at the time of surgery were included. All patients underwent accelerated corneal CXL. A thorough baseline and follow-up ophthalmic examination including uncorrected distance visual acuity, best corrected visual acuity (BCVA), slit-lamp and fundus examination, and corneal tomography by Scheimpflg camera Pentacam (Oculus, Wetzlar, Germany) were performed. RESULTS: The mean age of patients was 16.2 ± 1.8 years. Mean follow-up was 16.46 ± 11.6 months (range, 6-40 months). The mean BCVA improved significantly from 0.26 ± 0.26 to 0.16 ± 0.19 (logMAR) after accelerated CXL (P < 0.001). The mean corneal astigmatism based on refraction decreased from 3.69 ± 2.12 to 3.15 ± 1.86 after the intervention (P = 0.016). The mean maximum keratometry (Kmax) reduced significantly from 53.23 ± 6.07 diopter (D) to 52.23 ± 6.33 D (P = 0.047). The mean flat keratometry (K1) reduced from 46.37 ± 3.69 to 45.95 ± 3.65 after the intervention (P = 0.119). CONCLUSION: Our study shows that accelerated CXL increases visual acuity and stabilizes or improves keratometric indices in pediatric patients with progressive KCN without any serious complication for a mean follow-up time of 16 months.

Anticancer, antioxidant, and hepatoprotective activity of Saussurea lappa, C.B. clarke (qust) on human hepatoma cell line.

BACKGROUND: Liver cancer is considered as one of the most widespread malignancies across the globe. According to a recent estimate, about 782,000 people were diagnosed with liver cancer, out of which 746,000 people died. Conventional anticancer therapy cannot fulfill all the clinical needs due to accessibility, clinical efficacy, and safety issues. Hence, the need of novel inexpensive drugs from traditional medicine as potential chemotherapeutic agent becomes utmost urgent. Root of Saussurea lappa, C.B. Clarke (Unani name, qust) has been used in the Unani medicine for the treatment of chronic liver diseases (warm-e-jigar sulb) including hepatocellular carcinoma since centuries. OBJECTIVE: The objective is to study the anti-cancerous, antioxidant, and hepatoprotective activity of different extracts of SLE in vitro. MATERIALS AND METHODS: MTT assay was used to determine the anticancer activity and EC50 of SLEs. Cell viability and cell inhibition were calculated. Apoptosis was studied by DAPI 4',6-diamidino-2-phenylindole (DAPI) staining. Thein vitro hepatotoxicity of CCl4 was produced and hepatoprotective properties of different concentrations of ethanolic (ESL), aqueous (ASL), and hydroethanolic extract of Saussurea lappa (HSL) have been evaluated by measuring cell viability in HepG2 cells. RESULTS: MTT assay revealed that the molecule reduced the cell viability of HepG2 cancer cells. Test drugs induced apoptosis in a concentration-dependent manner, as indicated by DAPI staining. In addition, ESL, ASL, and HSL also reduced the colony-forming potential of the HepG2 cell. ESL, ASL, and HSL were observed to protect the HepG2 cells from CCl4 induced injury in a dose-dependent manner. CONCLUSION: The observed effect substantiated the anti-cancerous, antioxidant, and hepatoprotective activity of SLEs in HepG2 Cells.

Update of hypothyroidism and its management in Unani medicine.

Hypothyroidism is a clinical syndrome caused by thyroid hormone deficiency due to reduced production, deranged distribution, or lack of effects of thyroid hormone. The prevalence of hypothyroidism in developed countries is around 4-5%, whereas it is about 11% in India, only 2% in the UK, and 4·6% in the USA. It is more common in women than in men. Hypothyroidism has multiple etiologies and manifestations. The most common clinical manifestations are weight gain, loss of hair, cold intolerance, lethargy, constipation, dry skin, and change in voice. The signs and symptoms of hypothyroidism differ with age, gender, severity of condition, and some other factors. The diagnosis is based on clinical history, physical examination and serum level of FT3, FT4, and thyroid-stimulating hormone, imaging studies, procedures, and histological findings. The treatment of choice for hypothyroidism is levothyroxine, however; in this review article, we have discussed the epidemiology, etiology, clinical sign and symptoms, diagnosis, complications, and management of hypothyroidism in modern medicine and a comparative treatment by the Unani system of medicine (USM). In the USM, the main emphasis of the principle of treatment (Usool-e-Ilaj) is to correct the abnormal constitution (Su-e-Mizaj) and alter the six prerequisites for existence (Asbab-e-Sitta Zarooriya) to restore normal health. It is a packaged treatment, that is, different components of treatment are given as a package form which includes different drugs, dosages form, and regimens.

Understanding COVID-19 in the light of epidemic disease described in Unani medicine.

Unani system of medicine is based on the humoral theory postulated by Hippocrates, according to him the state of body health and disease are regulated by qualitative and quantitative equilibrium of four humours. Amraz-e-Waba is an umbrella term which is used in Unani medicine for all types of epidemics (smallpox, measles, plague, Hameer Saifi, influenza, Nipaha, Ebola, Zika, and 2019 novel coronavirus, etc.) mostly fatal in nature. The coronavirus disease 2019 (COVID-19) is a severe acute respiratory infection, and the pathogenesis and clinical features resemble with those of Nazla-e-Wabaiya (influenza) and Zatul Riya (pneumonia) which were well described many years ago in Unani text such as high-grade fever, headache, nausea and vomiting, running nose, dry cough, respiratory distress, alternate and small pulse, asthenia, foul smell from breath, insomnia, frothy stool, syncope, coldness in both upper and lower extremities, etc. The World Health Organization declared COVID-19 as a global emergency pandemic. Unani scholars like Hippocrates (370-460 BC), Galen (130-200 AD), Rhazes (865-925 AD), and Avicenna (980-1037 AD) had described four etiological factors for Amraz-e-Waba viz., change in quality of air, water, Earth, and celestial bodies, accordingly mentioned various preventive measures to be adopted during epidemics such as restriction of movement, isolation or "quarantena", and fumigation with loban (Styrax benzoin W. G. Craib ex Hartwich.), sandalwood (Santalum album L.), Zafran (Crocus sativus L.), myrtle (Myrtus communis L.), and roses (Rosa damascena Mill.) and use of vinegar (sirka) and antidotes (Tiryaq) as prophylaxis, and avoiding consumption of milk, oil, sweet, meat, and alcohol. This review focuses and elaborates on the concept, prevention, and probable management of COVID-19 in the light of Amraz-e-Waba.

Understanding COVID-19 in the light of epidemic disease described in Unani medicine.

Unani system of medicine is based on the humoral theory postulated by Hippocrates, according to him the state of body health and disease are regulated by qualitative and quantitative equilibrium of four humours. Amraz-e-Waba is an umbrella term which is used in Unani medicine for all types of epidemics (smallpox, measles, plague, Hameer Saifi, influenza, Nipaha, Ebola, Zika, and 2019 novel coronavirus, etc.) mostly fatal in nature. The coronavirus disease 2019 (COVID-19) is a severe acute respiratory infection, and the pathogenesis and clinical features resemble with those of Nazla-e-Wabaiya (influenza) and Zatul Riya (pneumonia) which were well described many years ago in Unani text such as high-grade fever, headache, nausea and vomiting, running nose, dry cough, respiratory distress, alternate and small pulse, asthenia, foul smell from breath, insomnia, frothy stool, syncope, coldness in both upper and lower extremities, etc. The World Health Organization declared COVID-19 as a global emergency pandemic. Unani scholars like Hippocrates (370-460 BC), Galen (130-200 AD), Rhazes (865-925 AD), and Avicenna (980-1037 AD) had described four etiological factors for Amraz-e-Waba viz., change in quality of air, water, Earth, and celestial bodies, accordingly mentioned various preventive measures to be adopted during epidemics such as restriction of movement, isolation or "quarantena", and fumigation with loban (Styrax benzoin W. G. Craib ex Hartwich.), sandalwood (Santalum album L.), Zafran (Crocus sativus L.), myrtle (Myrtus communis L.), and roses (Rosa damascena Mill.) and use of vinegar (sirka) and antidotes (Tiryaq) as prophylaxis, and avoiding consumption of milk, oil, sweet, meat, and alcohol. This review focuses and elaborates on the concept, prevention, and probable management of COVID-19 in the light of Amraz-e-Waba.

Quality control, HPTLC analysis, antioxidant and antimicrobial activity of hydroalcoholic extract of roots of qust (Saussurea lappa, C.B Clarke).

OBJECTIVES: Saussurea lappa, CB Clarke (S.lappa) is a perennial herb of the Compositae family. The root of S.lappa has been used for the treatment of various diseases such as hepatitis, jaundice, intestinal worms, bronchial asthma, and a variety of skin diseases. The aim of the study was to ensure quality control of S.lappa and its preparation HAESL (hydroalcoholic extract of S.lappa) along with assessment of HAESL antimicrobial and antioxidant activities in vitro. METHODS: HAESL was prepared with 50% ethanol, (v/v). Physiochemical analysis of the root of S.lappa, and phytochemical screening, thin-layer chromatography (TLC), high-performance thin-layer chromatography (HPTLC), and in vitro antimicrobial and antioxidant activity of HAESL were performed using the standard protocol. RESULTS: Physiochemical and phytochemical assessments of S.lappa and HAESL showed the greater quality of the drug. HAESL showed the presence of many phytochemical constituents corresponding to colorful spots, peaks, area under the curve, and corresponding Rf values as evident in the TLC and HPTLC analysis. HAESL showed a concentration-dependent effect on radical scavenging activity against DPHH (2,2-diphenyl-1-picrylhydrazyl) and hydroxyl radical with IC50 value of 19.10 µg/mL and 82.23 µg/mL, respectively. HAESL exhibited antimicrobial activity against the growth of micro-organisms such as Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhi, Aspergillus flavus, and Candida albicans. HASEL showed no antimicrobial activity against Aspergillus niger. CONCLUSIONS: The procured and an identified sample of Saussurea lappa was good in quality and the prepared HAESL contained many phytochemical compounds. HAESL substantiated significant antioxidant and antimicrobial activity in vitro.

Management Strategies of Ocular Abnormalities in Patients with Marfan Syndrome: Current Perspective.

Marfan syndrome is an autosomal dominant genetic connective tissue disorder that results from mutations in the fibrillin-1 gene located on chromosome band 15q15-21. Fibrillin, a glycoprotein, is widely expressed throughout the body and contributes to the elasticity and force-bearing capacity of connective tissue. In the eye, fibrillin is a key constituent of the ciliary zonules, which suspend the crystalline lens in place. The zonular defect leads to ectopia lentis, which is a hallmark of Marfan ocular abnormalities and occurs in 60% to 80% of cases. Other less common ocular features of Marfan syndrome are increased axial length, astigmatism, and flat cornea. Visual function in Marfan syndrome could be affected in several ways: ectopia lentis, refractive error, amblyopia, retinal detachment, cataract, and glaucoma. Management of a subluxated lens starts with the correction of refractive error with eyeglasses in mild cases. In more severe cases, especially when the lens bisects the pupil, complete correction of refractive error is impossible without removing the subluxated lens. The best method for visual rehabilitation after lens extraction is still debated. Aphakic Artisan lens implantation at the time of subluxated lens removal results in good visual outcomes with an acceptable safety profile. Studies with longer term follow-up and larger sample populations are needed to evaluate the safety of this procedure in patients with Marfan syndrome.

Corneal profile in primary congenital glaucoma.

PURPOSE: To investigate biomechanical and ultrastructural corneal parameters and ocular biometrics in the affected eyes of patients with unilateral primary congenital glaucoma (PCG) as compared to unaffected fellow eyes and age-matched healthy controls. METHODS: A total of 12 patients with treated unilateral PCG and 10 normal subjects were evaluated. LENSTAR was performed to determine biometric parameters; the ocular response analyser was employed to determine biomechanical properties and slit-scanning confocal microscopy was used for evaluation of corneal ultrastucture. RESULTS: Axial length was significantly higher and mean keratometry in affected eyes was significantly flatter in affected eyes as compared to fellow eyes and normal controls (p < 0.05), and a negative correlation was present between axial length and mean keratometry (p < 0.05). Mean aqueous depth and anterior chamber depth were increased in affected eyes as compared to fellow eyes and normal controls (p < 0.05). There was no significant difference in central corneal thickness (CCT) among affected eyes, fellow eyes and normal controls. Corneal hysteresis (CH) was significantly reduced in affected eyes (p < 0.05) and corneal resistance factor (CRF) was also reduced in the affected eyes as compared to fellow eyes and normal controls, although not statistically significant. Mean endothelial cell density was reduced in the affected eyes compared to fellow eyes and normal controls (p < 0.05). CONCLUSION: Corneal biometrics, biomechanical parameters and ultrastructural features are altered in eyes affected with PCG despite clinically normal and clear corneas. These findings should be considered in the preoperative assessment of intraocular or corneal surgery in these patients.

Ocular Safety of Intravitreal Connective Tissue Growth Factor Neutralizing Antibody.

PURPOSE: To detect the safety of intravitreal injection of anti-connective tissue growth factor (CTGF) (IVAC) in rat eyes in order to apply this neutralizing antibody for experimental animal studies. METHODS: Forty-five Lister Hooded male pigmented rats were divided into five groups that received IVAC (2 µl) corresponding to the doses of 10 (B), 20 (C), 50 (D), and 100 µg/ml (E), equal to 1.25, 2.5, 6.25, and 12.5 µg/ml of antibody concentration in rat vitreous, respectively. The sham group (A) received 2 µl of normal saline. Full field electroretinography (ERG) was performed at baseline and on days 7 and 28 after IVAC. The animals were euthanized and the corresponding eyes were subjected to routine histopathology, immunohistochemistry for glial fibrillary acidic protein (GFAP), and terminal transferase dUTP nick end-labeling (TUNEL) assay. RESULTS: Scotopic rod b-wave amplitude and maximal combined b-wave amplitude were 111.89 ± 71.2 and 178.57 ± 55.58 µV, respectively, at baseline which significantly reduced to 79.31 ± 52.59 and 128.73 ± 41.61 µV, respectively, after 28 days in group E (p < 0.05). There was no significant reduction of amplitudes in other groups with lower doses of anti-CTGF antibody. Retinal ganglion cells were significantly decreased in group E as compared to other groups. GFAP immune reactivity was not significant in any of the groups. TUNEL test showed inner retinal neural cell apoptosis only in group E. CONCLUSIONS: ERG, histopathologic, and apoptotic assays revealed no toxic effects of 10-50 µg/ml of IVAC in rat eyes. Using 100 µg/ml IVAC led to a significant toxic effect in terms of functional, histopathologic, and TUNEL findings.

Guidelines for guidelines: are they up to the task? A comparative assessment of clinical practice guideline development handbooks.

OBJECTIVES: We conducted a comparative review of clinical practice guideline development handbooks. We aimed to identify the main guideline development tasks, assign weights to the importance of each task using expert opinions and identify the handbooks that provided a comprehensive coverage of the tasks. METHODS: We systematically searched and included handbooks published (in English language) by national, international or professional bodies responsible for evidenced-based guideline development. We reviewed the handbooks to identify the main guideline development tasks and scored each handbook for each task from 0 (the handbook did not mention the task) to 2 (the task suitably addressed and explained), and calculated a weighted score for each handbook. The tasks included in over 75% of the handbooks were considered as 'necessary' tasks. RESULT: Nineteen guideline development handbooks and twenty seven main tasks were identified. The guideline handbooks' weighted scores ranged from 100 to 220. Four handbooks scored over 80% of the maximum possible score, developed by the National Institute for Health and Clinical Excellence, Swiss Centre for International Health, Scottish Intercollegiate Guidelines Network and World Health Organization. Necessary tasks were: selecting the guideline topic, determining the guideline scope, identifying relevant existing guidelines, involving the consumers, forming guideline development group,, developing clinical questions, systematic search for evidence, selecting relevant evidence, appraising identifies research evidence, making group decision, grading available evidence, creating recommendations, final stakeholder consultation, guideline implementation strategies, updating recommendations and correcting potential errors. DISCUSSION: Adequate details for evidence based development of guidelines were still lacking from many handbooks. The tasks relevant to ethical issues and piloting were missing in most handbooks. The findings help decision makers in identifying the necessary tasks for guideline development, provide an updated comparative list of guideline development handbooks, and provide a checklist to assess the comprehensiveness of guideline development processes.