Safety and efficacy of a Siddha Medicine fixed regimen for the treatment of asymptomatic and mild COVID-19 patients.

Background: The Coronavirus disease 2019 (COVID-19) pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a massive threat to public health worldwide. Siddha system of medicine is one of the traditional medicines of South India. The recommended formulations in Siddha Sasthric Medicines- Fixed Regimen (SSM-FiRe) are Amukkura tablets, Kaba Sura Kudineer (KSK) for asymptomatic COVID-19 positive (RT-PCR) patients, and Athimathuram tablets, Adathodai Manappagu syrup, Thippili Rasayanam, Brahmananda Bairavam tablet, and Notchi Kudineer for mild symptomatic patients. The core objective of the trial was to document the efficacy of SSM-FiRe in the prevention of asymptomatic and mild COVID-19 disease progression to the next level of severity, reduce the severity of symptoms and revert to RT-PCR Negative. Methods: An exploratory, prospective, open-labeled, single-arm, non-randomized trial was designed as per GCP guidelines to assess the efficacy of SSM-FiRe. Sixty RT-PCR positive participants who were asymptomatic or with mild COVID-19 symptoms were recruited for the study at the Siddha COVID Care Centre, Vyasarpadi, Chennai from June to August 2020. Nasal and oropharyngeal swab tests were performed on the 0, 7th, and 14th days. All participants were treated with SSM - FiRe regimen. All the participants were also assessed based on Siddha Yakkkaiyin Ilakkanam, which included Clinical symptoms and vitals. Laboratory investigations such as Haemogram, Liver Function Test, Renal Function Test, HbA1C, Electrolytes, Inflammatory markers, Cardiac profile, Immunoglobulins, and anti-SARS-CoV-2 antibody tests were performed. Results: 83% of COVID-19 patients turned RT-PCR negative on the 7th day and in most of the cases, symptoms were reduced within the first 5 days of admission. The RT-PCR cycle threshold (ct) value increased significantly (<0.001) after treatment and all the participants were RT-PCR negative, except one, who was positive even after 14 days. Anti-SARS-CoV-2 antibodies developed significantly (p-value - 0.006). LFT, RFT, CBC, Total proteins, and electrolytes continued to be in the normal range after treatment, indicating the safety of the intervention. Conclusion: Asymptomatic and mild COVID-19 disease can be well managed by SSM - FiRe treatment, Further studies could be taken up to strengthen the findings.

Antiviral activity of ethanolic extract of Nilavembu Kudineer against dengue and chikungunya virus through in vitro evaluation.

BACKGROUND: Currently, no vaccines or modern drugs are available for dengue and chikungunya and only symptomatic relief is provided to the patients. Siddha medicine, a traditional form of indigenous medical system uses specific polyherbal formulations for the treatment of such infections with considerable success. One such polyherbal formulation for the treatment of chikungunya and dengue is Nilavembu kudineer (NVK). The mechanistic details of this drug as an antiviral for chikungunya virus (CHIKV) and dengue virus (DENV) is poorly understood. OBJECTIVES: The current study was undertaken to study the efficacy of NVK as an antiviral formulation against CHIKV and DENV. MATERIALS AND METHODS: Cytotoxicity assays (MTT) were performed to determine the role of NVK as an antiviral during chikungunya and dengue infections in the following conditions-i). post infection, ii). during active infections and iii) protective, not allowing virus infection. RESULTS: It was observed that NVK provides protection against CHIKV and DENV-2 during active infection as well can help to prevent virus infection in the cells and it mainly depends on the cellular availability of drugs for maximum protection against both the infections. CONCLUSION: Our study establishes that extraction protocols are important to ensure maximum efficacy of NVK along with the time of addition of the drug during CHIKV and DENV infections in the cells. This study provides insights to the possible mode of action of NVK in in vitro condition during CHIKV and DENV infection.

Surgery for Blue Rubber Bleb Nevus Syndrome-a Case Report.

Blue rubber bleb nevus syndrome (BRBNS) is a rare disease characterised by multiple venous malformations and haemangioma in the skin and visceral organs. The lesion often involves the cutaneous and gastrointestinal tract. Most common visceral organ affected is the GIT. Most predominant region involved in the GIT is small bowel. However, vascular lesions can occur anywhere from oral mucosa to anal canal. GIT bleed is relatively slow, resulting in minor, chronic and occult blood loss. The syndrome in the GIT may also present with severe complications such as rupture, volvulus, intussusceptions and even death. Cutaneous malformations are usually asymptomatic and do not require treatment. The treatment of GIT lesions is determined by the extent of intestinal involvement and severity of the disease. Most patients respond to supportive therapy such as iron supplementation and blood transfusion. Surgical resection, endoscopic sclerosis and laser photocoagulation have been proposed for more significant haemorrhage and severe complications. Here, we present a case of BRBNS in a 13-year-old girl involving the GIT especially the large bowel, presenting with the complaints of bleeding per rectum and iron deficiency anaemia. Initially, endoscopic sclerotherapy was performed, but to no response. Hence, proceeded with surgical resection.

Electrochemical surface engineering of magnesium metal by plasma electrolytic oxidation and calcium phosphate deposition: biocompatibility and in vitro degradation studies.

In this study, the surface of magnesium metal was electrochemically engineered for enhanced biocompatibility and controlled degradation in body fluid. Firstly, a plasma electrolytic oxidation (PEO) coating was formed on magnesium, followed by electrochemical deposition of calcium phosphate (CaP) using an unconventional electrolyte. Cytocompatibility tests using L929 cells revealed that the PEO-CaP coating significantly improved the biocompatibility of magnesium. In vitro electrochemical degradation experiments in simulated body fluid (SBF) showed that the PEO-CaP coating improved the degradation resistance of magnesium significantly. The corrosion current density (i corr) of the PEO-CaP coated magnesium was ∼99% and ∼97% lower than that of bare magnesium and the PEO-only coated magnesium, respectively. Similarly, electrochemical impedance spectroscopy (EIS) results showed that the polarisation resistance (R P) of the PEO-CaP coated magnesium was one-order of magnitude higher as compared to the PEO-only coated magnesium and two-orders of magnitude higher than the bare magnesium, after 72 h immersion in SBF. Scanning electron microscopy (SEM) analysis revealed no localized degradation in the PEO-CaP coated magnesium. The study demonstrated that the PEO-CaP coating is a promising combination for enhancing the biocompatibility and reducing the degradation of magnesium for potential biodegradable implant applications.

Biocompatibility and in Vitro Degradation Behavior of Magnesium-Calcium Alloy Coated with Calcium Phosphate Using an Unconventional Electrolyte.

Calcium phosphate (CaP) was electrochemically coated on a magnesium-calcium (Mg-Ca) alloy using an unconventional electrolyte and a pulse-potential method. The CaP particles of the coating were relatively large, flat, and irregularly oriented; however, they covered the entire alloy surface with a coating thickness of 5 µm. Cytocompatibility tests using L929 cells inoculated in Eagle minimum essential medium supplemented with 10% (v/v) fetal bovine serum (E-MEM+FBS) revealed that CaP coating improved the cytocompatibility of the alloy. It also showed effective suppression of Mg2+ ion release from the substrate of the coated alloy and consequently reduced the pH increase of the medium. In vitro degradation experiments using electrochemical techniques in simulated body fluid (SBF) also suggested significant enhancement of the alloy degradation resistance by CaP coating. Potentiodynamic polarization results showed that the corrosion current density of the coated alloy was ∼95% lower than that of the bare metal. Electrochemical impedance spectroscopy results revealed that the polarization resistance (RP) of the coated alloy was more than an order of magnitude higher than that of the bare metal after 2 h of immersion in SBF. Interestingly, after 72 h of immersion, the measured RP had decreased by ∼82%, and the coating appeared cracked and damaged. The results suggest that SBF is more aggressive than E-MEM+FBS cell culture medium.

Tailored magnetic nanoparticles for optimizing magnetic fluid hyperthermia.

Magnetic Fluid Hyperthermia (MFH) is a promising approach towards adjuvant cancer therapy that is based on the localized heating of tumors using the relaxation losses of iron oxide magnetic nanoparticles (MNPs) in alternating magnetic fields (AMF). In this study, we demonstrate optimization of MFH by tailoring MNP size to an applied AMF frequency. Unlike conventional aqueous synthesis routes, we use organic synthesis routes that offer precise control over MNP size (diameter ∼10 to 25 nm), size distribution, and phase purity. Furthermore, the particles are successfully transferred to the aqueous phase using a biocompatible amphiphilic polymer, and demonstrate long-term shelf life. A rigorous characterization protocol ensures that the water-stable MNPs meet all the critical requirements: (1) uniform shape and monodispersity, (2) phase purity, (3) stable magnetic properties approaching that of the bulk, (4) colloidal stability, (5) substantial shelf life, and (6) pose no significant in vitro toxicity. Using a dedicated hyperthermia system, we then identified that 16 nm monodisperse MNPs (σ-0.175) respond optimally to our chosen AMF conditions (f = 373 kHz, H0 = 14 kA/m); however, with a broader size distribution (σ-0.284) the Specific Loss Power (SLP) decreases by 30%. Finally, we show that these tailored MNPs demonstrate maximum hyperthermia efficiency by reducing viability of Jurkat cells in vitro, suggesting our optimization translates truthfully to cell populations. In summary, we present a way to intrinsically optimize MFH by tailoring the MNPs to any applied AMF, a required precursor to optimize dose and time of treatment.

Mode of action of calcium antagonists on responses to spasmogens and antigen challenge in human airway smooth muscle.

Calcium antagonists have been shown to inhibit exercise-induced asthma. The mechanism of inhibition is unclear, but may involve inhibition of mediator release and/or blockade of the mediator effects. We studied the effects of methoxyverapamil (D600) on human airway responses to spasmogens as well as on histamine release from passively sensitized human lung challenged with ragweed antigen. The concentrations of D600 required to inhibit 50% of the spasmogen responses (IC50) were calculated from the concentration-response relationships and were: histamine 4 x 10(-6) M; KCl 7 x 10(-7) M; leukotriene C4 4 x 10(-5) M; electrical field stimulation 5 x 10(-5) M; and for ragweed antigen in passively sensitized muscle 2 x 10(-6) M. Histamine release by antigen challenge from sensitized lung fragments was not blocked by D600, up to a concentration of 10(-5) M. The data suggest that the contractile effects of agonists are mediated through voltage- and receptor-operated calcium channels. The differential inhibitory effects of D600 on antigen-induced mediator release vs the smooth muscle effects of the various agonists may suggest multiple mechanisms of release or sources of mediators in human airway anaphylaxis.

Mechanisms of alpha-adrenoceptor mediated contractions of rat mesenteric artery.

The nature of the calcium channels associated with the activation of alpha-adrenoceptors in vascular smooth muscle has been investigated. The inhibitory effects of nitrendipine, a calcium antagonist, were studied on the contractions elicited by alpha-adrenoceptor agonists in rat superior mesenteric artery. Responses to equieffective concentrations of phenylephrine (alpha 1-adrenoceptor agonist), clonidine and BHT-920, (alpha 2-adrenoceptor agonists), and noradrenaline (nonselective agonist) were inhibited differentially by the calcium antagonist, with the sensitivity order being as follows: BHT-920 = clonidine greater than phenylephrine greater than noradrenaline. When the contractions to two doses of noradrenaline were compared, the low dose response was more sensitive to nitrendipine inhibition than the high dose response. This differential inhibition was not seen for noradrenaline in the presence of verapamil or for phenylephrine in the presence of nitrendipine. The contractions of the vessel to the agonists in zero calcium conditions were not significantly different from each other. The sensitivity differences among the agonists to nitrendipine may arise from differences in the postreceptor mechanisms of activation. The differential sensitivity of noradrenaline responses suggests a greater heterogeneity of calcium channels than those available for the other agonists.