Ameliorative action of <Emphasis Type="Italic">Vernonia cinerea</Emphasis> L. on cyclophosphamide-induced immunosuppression and oxidative stress in mice

Cyclophosphamide (CTX) is a widely used antineoplastic drug, which could cause toxicity to normal cells due to its toxic metabolites. The use of CTX in treating cancer patients is limited due to its severe toxicity induced mainly by oxidative stress. The present study reports the protective role of Vernonia cinerea L. against the CTX-induced toxicity in Balb/c mice. Intraperitoneal administration of the extract significantly increased the total WBC Count, bone marrow cellularity, α-esterase positive cells, and weights of lymphoid organs in CTX-treated animals, when compared with CTX control mice. Administration of V. cinerea was found to reduce the enhanced level of alkaline phosphatase, glutamate pyruvate transaminase, lipid peroxidation, and also significantly increased the reduced glutathione level in CTX-treated animals. Histopathological analysis of small intestine also suggests that extract could reduce the CTX-induced intestinal damage. The level of proinflammatory cytokine TNF-α, which was elevated during CTX administration, was significantly reduced by the V. cinerea extract administration. The lowered levels of other cytokines like IFN-γ, IL-2, GM-CSF, after CTX treatment were also found to be increased by extract administration. Administration of V. cinerea did not compromise the anti-neoplastic activity of CTX. Infact, there was a synergistic action of CTX and V. cinerea in reducing the solid tumors in mice. Methanolic extract of V. cinerea given intraperitoneally (i.p.) showed a significant chemoprotective activity without compromising the chemotherapeutic efficacy of CTX, indicating its possible use as an adjuvant during chemotherapy.     

Anti-diabetic and anti-cholesterolemic activity of methanol extracts of three species of Amaranthus

Objective

To investigate the anti-diabetic and anti-cholesterolemic activity of methanol extracts of leaves of Amaranthus caudatus, Amaranthus spinosus and Amaranthus viridis in normal and streptozotocin (STZ) induced diabetic rats.

Methods

In this study, the anti-diabetic and anti-cholesterolemic activity of methanol extracts of leaves of all three plants was evaluated by using normal and STZ induced diabetic rats at a dose of 200 mg/kg and 400 mg/kg p.o. daily for 21 days. Blood glucose levels and body weight were monitored at specific intervals, and different biochemical parameters, serum cholesterol, serum triglyceride, high density lipoprotein, low density lipoprotein and very low density lipoprotein were also assessed in the experimental animals. Histology of pancreas was performed.

Results

It was found that all the three plants at 400 mg/kg dose showed significant anti-diabetic and anti-cholesterolemic activity (P<0.01), while at 200 mg/kg dose less significant anti-diabetic activity (P<0.05) was observed.

Conclusions

Methanol extracts of Amaranthus caudatus, Amaranthus spinosus and Amaranthus viridis showed significant anti-diabetic and anti-cholesterolemic activity, which provides the scientific proof for their traditional claims.     

Management of squamous cell carcinoma of unknown origin in cervical lymph nodes

Forty-three patients with the diagnosis of metastatic squamous cell carcinoma from unknown primary to the cervical lymph nodes were treated in EOVAMC between 1962-1982. Six of these patients were N1, 19 N2, and 18 N3. Five-year survival was 41 per cent for N1, 15 per cent for N2, and 6 per cent for N3 nodes. There was no significant difference in the treatment failure of those patients treated with unimodality versus multimodality. A subsequent primary was detected in the head and neck in 23 per cent of these patients (10/43), and eight of these patients had received previous radiotherapy. The most common site for these subsequent primaries was hypopharynx. Nine of the 43 patients developed distant metastasis with no correlation to stage of disease or treatment modality. These data show that the survival of these patients correlates with the stage of nodal disease, and that radiotherapy did not decrease the subsequent appearance of the primary lesions.     

COVID-19 Vaccination Coverage,Intent, Knowledge,Attitudes, and Beliefs among Essential Workers,United States

We assessed coronavirus disease vaccination and intent and knowledge, attitudes, and beliefs among essential workers during March–June 2021. Coverage was 67%; 18% reported no intent to get vaccinated. Primary concerns were potential side effects, safety, and lack of trust in vaccines, highlighting the importance of increasing vaccine confidence in this population.     

Microwave-assisted preparation of a silver nanoparticles/N-doped carbon dots nanocomposite and its application for catalytic reduction of rhodamine B,methyl red and 4-nitrophenol dyes

In the current work, a silver nanoparticles/nitrogen-doped carbon dots (AgNPs/NCDs) nanocomposite was prepared by a microwave-assisted method that does not require additional reducing or stabilizing agents. Multiple analytical techniques were used to characterize the prepared nanocomposite. The nanocomposite exhibited a surface plasmon resonance (SPR) absorption peak at 420 nm, indicating the development of AgNPs with NCDs. Further, HRTEM results confirmed the formation of the nanocomposite with the appearance of lattice fringes of both materials. Additionally, the nanocomposite did not show any precipitation even after two months of storage. The nanocomposite exhibited high catalytic activity towards the reduction of rhodamine B (RhB, 98.83%), methyl red (MR, 97.14%) and 4-nitrophenol (4-NP, 99.95%) at ambient temperature. Besides, the kinetic analysis revealed that the reduction reaction followed pseudo-first-order kinetics and the calculated rate constants (k) for rhodamine B (RhB), methyl red (MR) and 4-nitrophenol (4-NP) were found to be 0.0296 s⁻¹, 0.0233 s⁻¹ and 0.029 s⁻¹, respectively. Moreover, it is a reusable and stable catalyst for reduction reactions up to five cycles without significant loss in catalytic activity. Finally, a plausible mechanism for the reduction of pollutants is also discussed in detail. As a whole, the prepared nanocomposite might display stunning behaviour for wastewater treatment applications.

A silver nanoparticles/nitrogen-doped carbon dots (AgNPs/NCDs) nanocomposite was prepared by a microwave-assisted method, and exhibited high catalytic activity towards the reduction of rhodamine B, methyl red and 4-nitrophenol at ambient temperature.     

Experience with caspofungin in the treatment of persistent fungemia in neonates.

OBJECTIVE: To review our experience of caspofungin in the treatment of persistent candidemia in the neonatal intensive care unit. STUDY DESIGN: This was a retrospective chart review on 13 infants in whom caspofungin was added to conventional antifungals (amphotericin B and/or fluconazole or flucytosine) for the treatment of refractory candidemia. RESULTS: A total of 12 infants were preterm (gestational age, 24 to 28 weeks) and one was term; the median birth weight was 800 g (range, 530 to 5600 g). Candidemia (Candida albicans in five, C. parapsilosis in six, C. albicans and C. parapsilosis in one and C. tropicalis in one) persisted despite 6 to 30 days of conventional antifungal therapy. After the addition of caspofungin, sterilization of blood cultures was achieved in 11 infants at the median time of 3 days (range, 1 to 21 days). Adverse events included thrombophlebitis (one patient), hypokalemia (two patients) and elevation of liver enzymes (four patients). Three infants had a second episode of candidemia and seven patients died. CONCLUSION: Caspofungin may be an efficacious addition for treatment of candidemia refractory to conventional antifungal therapy. This drug should be further investigated in neonates.     

Novel nonnucleoside inhibitor of hepatitis C virus RNA-dependent RNA polymerase

A novel nonnucleoside inhibitor of hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp), [(1R)-5-cyano-8-methyl-1-propyl-1,3,4,9-tetrahydropyano[3,4-b]indol-1-yl] acetic acid (HCV-371), was discovered through high-throughput screening followed by chemical optimization. HCV-371 displayed broad inhibitory activities against the NS5B RdRp enzyme, with 50% inhibitory concentrations ranging from 0.3 to 1.8 microM for 90% of the isolates derived from HCV genotypes 1a, 1b, and 3a. HCV-371 showed no inhibitory activity against a panel of human polymerases, including mitochondrial DNA polymerase gamma, and other unrelated viral polymerases, demonstrating its specificity for the HCV polymerase. A single administration of HCV-371 to cells containing the HCV subgenomic replicon for 3 days resulted in a dose-dependent reduction of the steady-state levels of viral RNA and protein. Multiple treatments with HCV-371 for 16 days led to a >3-log10 reduction in the HCV RNA level. In comparison, multiple treatments with a similar inhibitory dose of alpha interferon resulted in a 2-log10 reduction of the viral RNA level. In addition, treatment of cells with a combination of HCV-371 and pegylated alpha interferon resulted in an additive antiviral activity. Within the effective antiviral concentrations of HCV-371, there was no effect on cell viability and metabolism. The intracellular antiviral specificity of HCV-371 was demonstrated by its lack of activity in cells infected with several DNA or RNA viruses. Fluorescence binding studies show that HCV-371 binds the NS5B with an apparent dissociation constant of 150 nM, leading to high selectivity and lack of cytotoxicity in the antiviral assays.     

Protective effect of Andrographis paniculata and andrographolide on cyclophosphamide-induced urothelial toxicity

The protective effect of Andrograhis paniculata and andrographolide (ANDLE) against cyclophosphamide (CTX)-induced urothelial toxicity was investigated in this study. Pretreatment of Swiss albino mice with A paniculata extract (10 mg/dose/animal intraperitoneally [ip]) and ANDLE (500 microg/dose/animal ip) could significantly reduce CTX (1.5 nmol/kg body weight)-induced urothelial toxicity. Morphological and histopathological analysis of urinary bladder of CTX-treated mice showed severe inflammation and dark coloration, whereas A paniculata and ANDLE-treated mice showed almost normal bladder morphology. Elevation of urinary protein level (7.33 +/- 0.3 g/L) by CTX administration was reduced by A paniculata (3.78 +/- 0.4 g/L) and ANDLE treatment (4.19 +/- 0.1 g/L). Urinary urea N2 level, which was elevated after 48 hours of CTX administration (24.25 +/- 0.2 g/L) was found to be reduced by the treatment with A paniculata (14.19 +/- 0.5 g/L) and ANDLE (15.79 +/- 0.4 g/L). A decreased level of reduced glutahione (GSH) content in liver (2.81 +/- 0.1 nmol/mg protein) and bladder (1.20 +/- 0.2 nmol/mg protein) after CTX administration was also increased by the treatment with A paniculata (liver: 5.78 +/- 0.3 nmol/mg protein; bladder: 2.96 +/- 0.2 nmol/mg protein) and ANDLE (liver: 5.14 +/- 0.3 nmol/mg protein; bladder: 2.84 +/- 0.2 nmol/mg protein). Production of the proinflammatory cytokine, tumor necrosis factor-alpha, which was elevated during CTX administration, was found to be inhibited by A paniculata and ANDLE treatment. The lowered level of interleukin-2 and interferon-gamma during CTX treatment was elevated by the administration of A paniculata and ANDLE.