Functional differentiation of cytotoxic cancer drugs and targeted cancer therapeutics

There is no nationally or internationally binding definition of the term “cytotoxic drug” although this term is used in a variety of regulations for pharmaceutical development and manufacturing of drugs as well as in regulations for protecting medical personnel from occupational exposure in pharmacy, hospital, and other healthcare settings. The term “cytotoxic drug” is frequently used as a synonym for any and all oncology or antineoplastic drugs. Pharmaceutical companies generate and receive requests for assessments of the potential hazards of drugs regularly – including cytotoxicity. This publication is intended to provide functional definitions that help to differentiate between generically-cytotoxic cancer drugs of significant risk to normal human tissues, and targeted cancer therapeutics that pose much lesser risks. Together with specific assessments, it provides comprehensible guidance on how to assess the relevant properties of cancer drugs, and how targeted therapeutics discriminate between cancer and normal cells. The position of several regulatory agencies in the long-term is clearly to regulate all drugs regardless of classification, according to scientific risk based data. Despite ongoing discussions on how to replace the term “cytotoxic drugs” in current regulations, it is expected that its use will continue for the near future.     

Effect of combined mulberry leaf and fruit extract on liver and skin cholesterol transporters in high fat diet-induced obese mice

Obesity is an epidemic disease characterized by an increased inflammatory state and chronic oxidative stress with high levels of pro-inflammatory cytokines and lipid peroxidation. Moreover, obesity alters cholesterol metabolism with increases in low-density lipoprotein (LDL) cholesterols and triglycerides and decreases in high-density lipoprotein (HDL) cholesterols. It has been shown that mulberry leaf and fruit ameliorated hyperglycemic and hyperlipidemic conditions in obese and diabetic subjects. We hypothesized that supplementation with mulberry leaf combined with mulberry fruit (MLFE) ameliorate cholesterol transfer proteins accompanied by reduction of oxidative stress in the high fat diet induced obesity. Mice were fed control diet (CON) or high fat diet (HF) for 9 weeks. After obesity was induced, the mice were administered either the HF or the HF with combination of equal amount of mulberry leaf and fruit extract (MLFE) at 500mg/kg/day by gavage for 12 weeks. MLFE treatment ameliorated HF induced oxidative stress demonstrated by 4-hydroxynonenal (4-HNE) and modulated the expression of 2 key proteins involved in cholesterol transfer such as scavenger receptor class B type 1 (SR-B1) and ATP-binding cassette transporter A1 (ABCA1) in the HF treated animals. This effect was mainly noted in liver tissue rather than in cutaneous tissue. Collectively, this study demonstrated that MLFE treatment has beneficial effects on the modulation of high fat diet-induced oxidative stress and on the regulation of cholesterol transporters. These results suggest that MLFE might be a beneficial substance for conventional therapies to treat obesity and its complications.     

An In Vitro Stereomicroscopic Evaluation of Bioactivity between Neo MTA Plus,Pro Root MTA,BIODENTINE & Glass Ionomer Cement Using Dye Penetration Method

The ideal root end filling material should form a tight seal in the root canal by adhering to the cavity walls. Several materials have been used for root end filling. The present study aims to find out and compare the bioactivity of Neo MTA Plus, Pro Root MTA White, BIODENTINE & glass ionomer cement as root end filling materials using 1% methylene blue as tracer. Materials and methods: 80 extracted human permanent maxillary anterior teeth were used in the study. They were divided into four groups. Specimens were sectioned transversely in the cervical area to separate the crown from the root. The root canal was obturated with gutta percha and zinc oxide eugenol sealers. Thereafter, each sample was resected apically by removing 3 mm of the apex and filled with different materials. Samples were kept in buffering solution at 37 °C until the recommended evaluation periods. The specimens were then suspended in 1% methylene blue for 24 h, prior to the analysis. The teeth were then sectioned, and dye penetration was examined, photographed, and evaluated under a stereomicroscope. Results: Vertical dye penetration showed significant differences across different groups. The minimum dye penetration was seen in Neo MTA plus followed by BIODENTINE, Pro Root MTA and maximum in GIC. There was no significant difference in dye penetration between Neo MTA plus and BIODENTINE both at fifteen days and one-month intervals. Conclusion: The present study suggests Neo MTA plus and BIODENTINE should be the preferred material for root end filling.     

Phage-Displayed Peptides for Targeting Tyrosine Kinase Membrane Receptors in Cancer Therapy

Receptor tyrosine kinases (RTKs) regulate critical physiological processes, such as cell growth, survival, motility, and metabolism. Abnormal activation of RTKs and relative downstream signaling is implicated in cancer pathogenesis. Phage display allows the rapid selection of peptide ligands of membrane receptors. These peptides can target in vitro and in vivo tumor cells and represent a novel therapeutic approach for cancer therapy. Further, they are more convenient compared to antibodies, being less expensive and non-immunogenic. In this review, we describe the state-of-the-art of phage display for development of peptide ligands of tyrosine kinase membrane receptors and discuss their potential applications for tumor-targeted therapy.     

Feline Morbillivirus Infection in Domestic Cats: What Have We Learned So Far?

Feline morbillivirus (FeMV) was identified for the first time in stray cats in 2012 in Hong Kong and, since its discovery, it was reported in domestic cats worldwide. Although a potential association between FeMV infection and tubulointerstitial nephritis (TIN) has been suggested, this has not been proven, and the subject remains controversial. TIN is the most frequent histopathological finding in the context of feline chronic kidney disease (CKD), which is one of the major clinical pathologies in feline medicine. FeMV research has mainly focused on defining the epidemiology, the role of FeMV in the development of CKD, and its in vitro tropism, but the pathogenicity of FeMV is still not clear, partly due to its distinctive biological characteristics, as well as to a lack of a cell culture system for its rapid isolation. In this review, we summarize the current knowledge of FeMV infection, including genetic diversity of FeMV strains, epidemiology, pathogenicity, and clinicopathological findings observed in naturally infected cats.     

Detection of Genotype-Specific Antibody Responses to Glycoproteins B and H in Primary and Non-Primary Human Cytomegalovirus Infections by Peptide-Based ELISA

Background: Strain-specific antibodies to human cytomegalovirus (HCMV) glycoproteins B and H (gB and gH) have been proposed as a potential diagnostic tool for identifying reinfection. We investigated genotype-specific IgG antibody responses in parallel with defining the gB and gH genotypes of the infecting viral strains. Methods: Subjects with primary (n = 20) or non-primary (n = 25) HCMV infection were studied. The seven gB (gB1-7) and two gH (gH1-2) genotypes were determined by real-time PCR and whole viral genome sequencing, and genotype-specific IgG antibodies were measured by a peptide-based enzyme-linked immunosorbent assay (ELISA). Results: Among subjects with primary infection, 73% (n = 8) infected by gB1-HCMV and 63% (n = 5) infected by gB2/3-HCMV had genotype-specific IgG antibodies to gB (gB2 and gB3 are similar in the region tested). Peptides from the rarer gB4-gB7 genotypes had nonspecific antibody responses. All subjects infected by gH1-HCMV and 86% (n = 6) infected by gH2-HCMV developed genotype-specific responses. Among women with non-primary infection, gB and gH genotype-specific IgG antibodies were detected in 40% (n = 10) and 80% (n = 20) of subjects, respectively. Conclusions: Peptide-based ELISA is capable of detecting primary genotype-specific IgG responses to HCMV gB and gH, and could be adopted for identifying reinfections. However, about half of the subjects did not have genotype-specific IgG antibodies to gB.     

Is the First of the Two Born Saved? A Rare and Dramatic Case of Double Placental Damage from SARS-CoV-2

The current coronavirus pandemic has affected, in a short time, various and different areas of medicine. Among these, the obstetric field has certainly been touched in full, and the knowledge of the mechanisms potentially responsible for placental damage from SARS-CoV-2 occupy a certain importance. Here we present here a rare case of dichorionic twins born at 30 weeks and 4 days of amenorrhea, one of whom died in the first few hours of life after placental damages potentially related to SARS-CoV-2. We also propose a brief review of the current literature giving ample emphasis to similar cases described.