Synthesis of Carvacrol Derivatives as Potential New Anticancer Agent against Lung Cancer.

Lung cancer remains a major public health concern among all cancer diseases due to the toxicity and side-effects of the available commercially synthesized drugs. Natural product-derived synthesized anticancer drugs are now of promising interest to fight against cancer death. Carvacrol is a major component of most essential oil-bearing plants with potential pharmacological activity, especially against various cancer cell lines. Among the other organometallic compounds, copper complexes have been reported to be effective anticancer agents against various cancer cell lines, especially lung and leukemia cancers, due to the nontoxic nature of copper in normal cells since it is an endogenic metal. In this study, we synthesized three carvacrol derivatives, i.e., carvacrol aldehyde, Schiff base, and copper-Schiff base complex, through an established synthesis protocol and characterized the synthesized product using various spectroscopic techniques. The synthesized derivatives were evaluated for in vitro cytotoxic activity against different cancer cell lines, including human lung cancer (A549) and human fibroblast (BALB-3T3). Our findings showed that the copper-Schiff base complex derived from carvacrol inhibited the proliferation and migration of the A549 cell lines in a dose-dependent manner. This activity might be due to the inhibition of cell proliferation and migration at the G2/M cell-cycle phase, as well as apoptosis, possibly through the activation of the mitochondrial apoptotic pathway. To our knowledge, this is the first report on the activity of the copper-Schiff base complex of carvacrol against A549 cell lines. Our result highlights that a new synthesized copper complex from carvacrol could be a novel potential drug in the treatment of lung cancer.

An Immunoinformatic-Based In Silico Identification on the Creation of a Multiepitope-Based Vaccination Against the Nipah Virus.

The zoonotic viruses pose significant threats to public health. Nipah virus (NiV) is an emerging virus transmitted from bats to humans. The NiV causes severe encephalitis and acute respiratory distress syndrome, leading to high mortality rates, with fatality rates ranging from 40% to 75%. The first emergence of the disease was found in Malaysia in 1998-1999 and later in Bangladesh, Cambodia, Timor-Leste, Indonesia, Singapore, Papua New Guinea, Vietnam, Thailand, India, and other South and Southeast Asian nations. Currently, no specific vaccines or antiviral drugs are available. The potential advantages of epitope-based vaccines include their ability to elicit specific immune responses while minimizing potential side effects. The epitopes have been identified from the conserved region of viral proteins obtained from the UniProt database. The selection of conserved epitopes involves analyzing the genetic sequences of various viral strains. The present study identified two B cell epitopes, seven cytotoxic T lymphocyte (CTL) epitopes, and seven helper T lymphocyte (HTL) epitope interactions from the NiV proteomic inventory. The antigenic and physiological properties of retrieved protein were analyzed using online servers ToxinPred, VaxiJen v2.0, and AllerTOP. The final vaccine candidate has a total combined coverage range of 80.53%. The tertiary structure of the constructed vaccine was optimized, and its stability was confirmed with the help of molecular simulation. Molecular docking was performed to check the binding affinity and binding energy of the constructed vaccine with TLR-3 and TLR-5. Codon optimization was performed in the constructed vaccine within the Escherichia coli K12 strain, to eliminate the danger of codon bias. However, these findings must require further validation to assess their effectiveness and safety. The development of vaccines and therapeutic approaches for virus infection is an ongoing area of research, and it may take time before effective interventions are available for clinical use.

Impact of quality management monitoring and intervention on central venous catheter dysfunction in the outpatient chemotherapy infusion setting.

PURPOSE: To assess the utility of maintaining and analyzing a quality-management database while investigating a subjectively perceived increase in the incidence of tunneled catheter and port dysfunction in a cohort of oncology outpatients. MATERIALS AND METHODS: All 152 patients undergoing lytic therapy (2-4 mg alteplase) of a malfunctioning indwelling central venous catheter (CVC) from January through June 2004 at a single cancer center in the United States were included in a quality-management database. Patients were categorized by time to device failure and the initial method of catheter placement (surgery vs interventional radiology). Data were analyzed after 3 months, and areas of possible improvement were identified and acted upon. Three months of follow-up data were then collected and similarly analyzed. RESULTS: In a 6-month period, 152 patients treated for catheter malfunction received a total of 276 doses of lytic therapy. A 3-month interim analysis revealed a disproportionately high rate (34%) of early catheter malfunction (ECM; <30 days from placement). Postplacement radiographs demonstrated suboptimal catheter positioning in 67% of these patients, all of whom had surgical catheter placement. There was a 50% absolute decrease in the number of patients presenting with catheter malfunction in the period from April through June (P < .001). Evaluation of postplacement radiographs in these patients demonstrated a 50% decrease in the incidence of suboptimal positioning (P < .05). CONCLUSIONS: Suboptimal positioning was likely responsible for some, but not all, cases of ECM. Maintenance of a quality-management database is a relatively simple intervention that can have a clear and important impact on the quality and cost of patient care.

Enhanced response of childhood psoriasis to narrow-band UV-B phototherapy with preirradiation use of mineral oil.

Studies in adults show that pretreatment with an optimal emollient may improve transmission of ultraviolet-B. In our study, we evaluated whether the preirradiation use of mineral oil enhanced the efficacy of narrow-band ultraviolet-B phototherapy in childhood psoriasis. Twenty children, aged 5 to 14 years with widespread, symmetrical psoriasis involving >20% body surface area were enrolled in a prospective, single-blind, controlled study. Mineral oil was applied prior to irradiation over one half of the body and the other half was emollient-free control. Narrow-band ultraviolet-B phototherapy was administered to whole body twice a week on nonconsecutive days with initial dose of 50 mJ/cm(2) and increment of 10% at each session. Clinical response was evaluated as grades of erythema, scaling and induration, area of involvement and modified psoriasis area severity index score on each side at baseline, 3, 6, 9, and 12 weeks. Two patients dropped out, 18 patients completed the study. Significantly greater improvement (p < 0.05) in scaling, induration, area of involvement, and modified psoriasis area severity index score was seen on the mineral oil pretreated side as early as 3 weeks and was maintained throughout the study. Difference in erythema was noticed later at 6 weeks. The cumulative dose for clearance was significantly lower on the emollient pretreated side. No adverse effects were observed with mineral oil or narrow-band ultraviolet-B phototherapy. We conclude that preirradiation use of mineral oil enhances the therapeutic efficacy of narrow-band ultraviolet-B phototherapy in children with widespread psoriasis.

Selection of a thiazole urea-resistant variant of bovine viral diarrhoea virus that maps to the RNA-dependent RNA polymerase.

By passing wild type bovine viral diarrhoea virus (BVDV) in increasing concentrations of DPC-A69280-29, a thiazole urea class compound that inhibits BVDV replication, we were able to select several variants of BVDV that exhibited decreased susceptibility to this compound. When the non-structural genes of these variants were sequenced and compared with wild type, only one change was common to all the variants that also exhibited resistance to DPC-A69280-29 (>10-fold increase in IC50). This change was a T-to-A transversion at position 11198 of the BVDV genome, which would cause a predicted substitution of isoleucine for phenylalanine at amino acid 78 of the RNA-dependent RNA polymerase (RdRp). This substitution would occur in a region of the BVDV RdRp which has been proposed to be important for the formation of the RdRp homodimer that is essential for the activity of the enzyme. However, since DPC-69280-29 inhibits BVDV replication by interfering with the initiation of viral RNA synthesis, we discuss the possibility that this region of the BVDV RdRp also may play a role in the initiation process. Furthermore, since this region is located fairly close to the template RNA, we also propose that the role it plays may involve either template selection, stabilization or processivity.

Late onset isotretinoin resistant acne conglobata in a patient with acromegaly.

A 55 year-old male presented with multiple pus-discharging abscesses and sinuses and mutilating scarring on the gluteal region and back prevalent for the last ten years with exacerbations and remissions. Physical examination revealed acromegaly with frontal bossing, prognathism, a barrel chest and acral hypertrophy. Dermatological examination revealed cutis verticis gyrata, thick eyelids, a large triangular nose, a thickened lower lip, macroglossia, widely spaced teeth and widened skin pores with wet and oily skin. Hair was fine and nails were flat and wide. There were multiple inflammatory papules, tender nodules, draining sinuses, and grouped, polyporous comedones as well as multiple and extensive depressed and keloidal scars localized predominantly over the gluteal region with a few scattered lesions over the back. A computed tomography (CT) scan showed widened sella turcica. His basal fasting growth hormone (GH) levels were markedly raised (230 ng/mL; normal 1-5 ng/mL) while the prolactin levels were moderately raised (87 ng/mL; normal 2-5 ng/mL). These findings were consistent with a diagnosis of acromegaly. The patient was put on antibiotics, nonsteroidal antiinflammatory drugs and isotretinoin at a dose of 1 mg/kg/day, which was increased to 1.5 mg/kg/day. Except for an initial mildly beneficial response, the skin lesions were largely resistant to high doses of isotretinoin at the end of four months.

Inferior vena cava filter removal after 317-day implantation.

A Günther Tulip inferior vena cava (IVC) filter was placed prophylactically in a 22-year-old trauma victim with spinal injuries. Attempts to retrieve the filter at 21 and 25 days after placement were aborted as a result of clot trapped in the filter. Despite the possible risk of an IVC laceration, a third attempt was made 317 days after placement in view of the young age of the patient. The filter started collapsing into the retrieval sheath but could not easily be separated from the IVC. During attempted redeployment, the filter would not reopen. The filter was ultimately retrieved with use of additional force. A mild stenosis of the IVC was noted immediately after retrieval. However, the IVC returned to its preretrieval diameter as seen on a 3-month follow-up venogram.