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Materials (Basel, Switzerland) Sep 2019The physical and chemical characterization of the solid-state properties of drugs and excipients is fundamental for planning new formulations and developing new...
The physical and chemical characterization of the solid-state properties of drugs and excipients is fundamental for planning new formulations and developing new strategies for the treatment of diseases. Techniques such as differential scanning calorimetry, thermogravimetry, X-ray powder diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy are among the most commonly used techniques for these purposes. Penciclovir and lysine are individually used to treat the herpes virus. As such, the development of a formulation containing both drugs may have therapeutic potential. Solid-state characterization showed that both penciclovir and lysine were crystalline materials with melting points at 278.27 °C and 260.91 °C, respectively. Compatibility studies of penciclovir and lysine indicated a possible interaction between these substances, as evidenced by a single melting point at 253.10 °C. The compatibility of several excipients, including ethylenediaminetetraacetic acid, cetostearyl alcohol, sodium lauryl sulphate, di-tert-butyl methyl phenol, liquid petrolatum, methylparaben, nonionic wax, paraffin, propylene glycol, and propylparaben, was evaluated in ternary (penciclovir-lysine-excipient) mixtures (1:1:1, //) to determine the optimal formulation. The developed formulation was stable under accelerated and ambient conditions, which demonstrated that the interaction between penciclovir and lysine was suitable for the development of a formulation containing both drugs.
PubMed: 31569620
DOI: 10.3390/ma12193154 -
A novel monocyte differentiation pattern in pristane-induced lupus with diffuse alveolar hemorrhage.ELife Oct 2022Pristane causes chronic peritoneal inflammation resulting in lupus, which in C57BL/6 mice is complicated by lung microvascular injury and diffuse alveolar hemorrhage...
Pristane causes chronic peritoneal inflammation resulting in lupus, which in C57BL/6 mice is complicated by lung microvascular injury and diffuse alveolar hemorrhage (DAH). Mineral oil (MO) also causes inflammation, but not lupus or DAH. Since monocyte depletion prevents DAH, we examined the role of monocytes in the disease. Impaired bone marrow (BM) monocyte egress in /- mice abolished DAH, confirming the importance of monocyte recruitment to the lung. Circulating Ly6C monocytes from pristane-treated mice exhibited increased annexin-V staining in comparison with MO-treated controls without evidence of apoptosis, suggesting that pristane alters the distribution of phosphatidylserine in the plasma membrane before or shortly after monocyte egress from the BM. Plasma membrane asymmetry also was impaired in Nr4a1-regulated Ly6C 'patrolling' monocytes, which are derived from Ly6C precursors. Patrolling Ly6C monocytes normally promote endothelial repair, but their phenotype was altered in pristane-treated mice. In contrast to MO-treated controls, Nr4a1-regulated Ly6C monocytes from pristane-treated mice were CD138, expressed more TremL4, a protein that amplifies TLR7 signaling, and exuberantly produced TNFα in response to TLR7 stimulation. TremL4 expression on these novel CD138 monocytes was regulated by Nr4a1. Thus, monocyte CD138, high TremL4 expression, and annexin-V staining may define an activated/inflammatory subtype of patrolling monocytes associated with DAH susceptibility. By altering monocyte development, pristane exposure may generate activated Ly6C and Ly6C monocytes, contributing to lung microvascular endothelial injury and DAH susceptibility.
Topics: Mice; Animals; Monocytes; Mice, Inbred C57BL; Tumor Necrosis Factor-alpha; Mineral Oil; Phosphatidylserines; Toll-Like Receptor 7; Lung Diseases; Hemorrhage; Inflammation; Annexins
PubMed: 36264674
DOI: 10.7554/eLife.76205 -
Biosensors Oct 2021Mycoplasma pneumonia (MP) is a common respiratory infection generally treated with macrolides, but resistance mutations against macrolides are often detected in in...
Mycoplasma pneumonia (MP) is a common respiratory infection generally treated with macrolides, but resistance mutations against macrolides are often detected in in China. Rapid and accurate identification of and its mutant type is necessary for precise medication. This paper presents a 3D-printed microfluidic device to achieve this. By 3D printing, the stereoscopic structures such as microvalves, reservoirs, drainage tubes, and connectors were fabricated in one step. The device integrated commercial polymerase chain reaction (PCR) tubes as PCR chambers. The detection was a sample-to-answer procedure. First, the sample, a PCR mix, and mineral oil were respectively added to the reservoirs on the device. Next, the device automatically mixed the sample with the PCR mix and evenly dispensed the mixed solution and mineral oil into the PCR chambers, which were preloaded with the specified primers and probes. Subsequently, quantitative real-time PCR (qPCR) was carried out with the homemade instrument. Within 80 min, and its mutation type in the clinical samples were determined, which was verified by DNA sequencing. The easy-to-make and easy-to-use device provides a rapid and integrated detection approach for pathogens and antibiotic resistance mutations, which is urgently needed on the infection scene and in hospital emergency departments.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Lab-On-A-Chip Devices; Macrolides; Mineral Oil; Mutation; Mycoplasma pneumoniae; Printing, Three-Dimensional; Real-Time Polymerase Chain Reaction
PubMed: 34821643
DOI: 10.3390/bios11110427 -
Efficiency and sensitivity optimization of a protocol to quantify indoor airborne SARS-CoV-2 levels.The Journal of Hospital Infection Dec 2022Development of methodologies to quantify airborne micro-organisms is needed for the prevention and control of infections. It is difficult to conclude which is the most...
BACKGROUND
Development of methodologies to quantify airborne micro-organisms is needed for the prevention and control of infections. It is difficult to conclude which is the most efficient and sensitive strategy to assess airborne SARS-CoV-2 RNA levels due to the disparity of results reported in clinical settings.
AIM
To improve our previously reported protocol of measuring SARS-CoV-2 RNA levels, which was based on bioaerosol collection with a liquid impinger and RNA quantification with droplet digital polymerase chain reaction (ddPCR).
METHODS
Air samples were collected in COVID-19 patient rooms to assess efficiency and/or sensitivity of different air samplers, liquid collection media, and reverse transcriptases (RT).
FINDINGS
Mineral oil retains airborne RNA better than does hydrophilic media without impairing integrity. SARS-CoV-2 ORF1ab target was detected in 80% of the air samples using BioSampler with mineral oil. No significant differences in effectiveness were obtained with MD8 sampler equipped with gelatine membrane filters, but the SARS-CoV-2 copies/m air obtained with the latter were lower (28.4 ± 6.1 vs 9 ± 1.7). SuperScript II RT allows the detection of a single SARS-CoV-2 genome RNA molecule by ddPCR with high efficiency. This was the only RT that allowed the detection of SARS-CoV-2 N1 target in air samples.
CONCLUSION
The collection efficiency and detection sensivity of a protocol to quantify SARS-CoV-2 RNA levels in indoor air has been improved in the present study. Such optimization is important to improve our understanding of the microbiological safety of indoor air.
Topics: Humans; SARS-CoV-2; COVID-19; RNA, Viral; Mineral Oil
PubMed: 36100140
DOI: 10.1016/j.jhin.2022.08.011 -
Poultry Science Sep 2022This study was conducted to develop a recombinant Eimeria elongation factor-1α (EF-1α)-vaccination strategy against Eimeria maxima (E. maxima) infection by...
Co-administration of chicken IL-7 or NK-lysin peptide 2 enhances the efficacy of Eimeria elongation factor-1α vaccination against Eimeria maxima infection in broiler chickens.
This study was conducted to develop a recombinant Eimeria elongation factor-1α (EF-1α)-vaccination strategy against Eimeria maxima (E. maxima) infection by co-administering with chicken IL-7 (chIL-7) or chicken NK-lysin peptide 2 (cNK-2) in commercial broiler chickens. Chickens were divided into the following 5 groups: control (CON, no Eimeria infection), nonimmunized control (NC, PBS plus Montanide ISA 78 VG), Vaccination 1 (VAC1, 100 µg of recombinant EF-1α plus Montanide ISA 78 VG), Vaccination 2 (VAC2, VAC1 plus 1 µg of chIL-7), and Vaccination 3 (VAC3, VAC2 plus 5 µg of cNK-2 peptide). The first immunization except the cNK-2 injection was performed intramuscularly on day 4, and the secondary immunization was given with the same concentration of components as the primary immunization 1 wk later. All chickens except the CON group were orally inoculated with freshly prepared E. maxima (1.0 × 10 oocysts per chicken) oocysts on Day 19. The results of the in vivo vaccination trial showed that chickens of all groups immunized with recombinant EF-1α antigen (VAC1, VAC2, and VAC3) showed higher serum antibody levels to EF-1α, and co-injection with chIL-7 further increased the serum IL-7 level in the VAC2 and VAC3 groups. Chickens in the VAC2 group showed significantly (P < 0.01) higher body weight gains at 6 and 9 d post-E. maxima challenge infection (dpi) with reduced gut lesions in the jejunum at 6 dpi. The VAC3 group showed reduced fecal oocyst shedding compared to the nonimmunized and infected chickens (NC). At 4 dpi, E. maxima infection significantly (P < 0.05) up-regulated the expression levels of proinflammatory cytokines (IL-β and IL-17F) and type Ι cytokines (IFN-γ and IL-10) in the jejunum (NC), but the expression of these cytokines was significantly (P < 0.05) down-regulated in the VAC1, VAC2, and VAC3 groups. Furthermore, E. maxima challenge infection significantly (P < 0.05) down-regulated the expressions of jejunal tight junction (TJ) proteins (Jam2 and Occludin) at 4 dpi, but their expression was up-regulated in the VAC2 and VAC3 groups. Collectively, these results show the protective effects of the EF-1α recombinant vaccine, which can be further enhanced by co-injection with chIL-7 or cNK-2 peptide against E. maxima infection.
Topics: Adjuvants, Immunologic; Animals; Chickens; Coccidiosis; Cytokines; Eimeria; Eimeria tenella; Interleukin-7; Mineral Oil; Oocysts; Peptide Elongation Factor 1; Poultry Diseases; Proteolipids; Protozoan Vaccines; Vaccination; Vaccines, Synthetic
PubMed: 35905546
DOI: 10.1016/j.psj.2022.102013 -
Contrast Media & Molecular Imaging 2022Although the use of sterile petroleum jelly gauze combined with nanochitosan film to wrap wounds has been proven to have good results, it has not been applied for...
Although the use of sterile petroleum jelly gauze combined with nanochitosan film to wrap wounds has been proven to have good results, it has not been applied for modified Devine surgery. The use of sterile petroleum jelly gauze alone in the modified Devine surgery to treat concealed penis in children has different effects. In this study, the systematic evaluation of the effect of the modified Devine technique (Vaseline gauze bandaging the wound) in the treatment of concealed penis in children is conducted. Furthermore, the application of nanochitosan film and Vaseline gauze in the modified Devine technique is proposed. By analytical search in PubMed, China Knowledge Network (CKN), and other Chinese and foreign literature databases, there are 13 studies describing the development of the penis during the follow-up period with high satisfaction of patients and their family members. In addition, systematic evaluations have shown that the complete removal of the fibrotic penile sarcoid tissue is an important reason for the remarkable curative effect of the modified Devine surgery in the treatment of concealed penis in children.
Topics: Child; Humans; Male; Penis; Petrolatum
PubMed: 35845736
DOI: 10.1155/2022/9882966 -
Pharmaceutics Aug 2020Semisolid dosage forms are recommended for the dermal care of babies and children. If we look at the ingredients of these preparations, there are still many cases in...
Semisolid dosage forms are recommended for the dermal care of babies and children. If we look at the ingredients of these preparations, there are still many cases in which there are substances (occlusive agents, preservatives) that no longer meet certain requirements of the modern age, so it is timely to replace them with other substances. The aim of this work was to formulate a science-based formulation with new components that keep or improve its moisturizing properties, rheological parameters, and microbiological stability. Occlusive oils, like white petrolatum and liquid paraffin and the preservative parabens are traditional ingredients in oil in water creams, were replaced with white beeswax, sunflower oil, and phenoxyethanol, respectively. Cocoa butter, urea, and glycerol were added to improve long-lasting hydration and support the barrier function of the reformulated creams. The rheological properties of the formulations were determined. The effects of the preparations on skin hydration and on the barrier function of the skin were tested. Furthermore, microbiological stability was investigated. The result of the reformulation was an o/w cream that provided a good longer-lasting hydration effect; supported the barrier function of the baby skin without occlusion; and had adequate consistency, easy spreading, a pleasant skin feeling, proper pH, and good microbiological stability.
PubMed: 32759663
DOI: 10.3390/pharmaceutics12080729 -
International Journal of Pharmaceutics Jun 2022In vitro human skin permeation and distribution of the fragrance material linalool (3,7-dimethyl-1,6-octadien-3-ol, CAS No. 78-70-6) following application in a range of...
In vitro human skin permeation and distribution of the fragrance material linalool (3,7-dimethyl-1,6-octadien-3-ol, CAS No. 78-70-6) following application in a range of single and mixed vehicles was determined, under unoccluded and occluded conditions, using human epidermal membranes. Vehicles were (70/30 v/v) ethanol[EtOH]/water, dipropyleneglycol [DPG], diethyl phthalate [DEP], (25/75 v/v) EtOH/DEP, (25/75 v/v) EtOH/DPG and petrolatum. Worst case absorbed dose values (% applied dose) for linalool under unoccluded conditions varied from 1.84% (DPG) to 4.08% (EtOH/water) and under occluded conditions from 5.9% (DEP) to 14.7% (EtOH/water). Occlusion always increased absorption but the magnitude of the effect varied with the vehicle from 2 to 6-fold. This study demonstrated that in vitro human skin permeation of linalool varied quite widely between test vehicles and that the magnitude of the effect of occlusion was also vehicle dependent. This was particularly significant in view of the reported variations in biological responses using different vehicles (Lalko et al., 2004; Politano et al., 2006).
Topics: Acyclic Monoterpenes; Ethanol; Excipients; Humans; Pharmaceutical Vehicles; Skin; Skin Absorption; Water
PubMed: 35609833
DOI: 10.1016/j.ijpharm.2022.121826 -
Archives of Razi Institute Oct 2021Avian pasteurellosis (fowl cholera) is an important disease affecting domestic and wild birds all over the world. Although the capsular type A of is mostly involved,...
Avian pasteurellosis (fowl cholera) is an important disease affecting domestic and wild birds all over the world. Although the capsular type A of is mostly involved, other capsular types are occasionally incriminated. The present study aimed at investigating the effect of some adjuvants on immunogenicity and protectivity of bacterin in chickens, compared to an Iranian commercial vaccine. Eight-week-old chicken pullets were double vaccinated with an interval of three weeks. Vaccine immunogenicity testing was conducted using an in-house indirect enzyme-linked immunosorbent assay and assessing serum antibody titers at 7, 14, and 21 days post-primary and 14 days post-secondary immunization. The possible adverse effects were recorded by a poultry-disease expert. For evaluating the vaccine protection rate, chickens were subjected to 2×Lethal Dose 50%of a virulent strain two weeks post-secondary immunization. The rate of live and normal animals was regarded as protection rate 7days after the exposure. The findings showed that oil adjuvants Montanide ISA 70-and Montanide ISA 71-containingvaccines (with or without saponin) caused a powerful immune reaction than the aluminum adjuvanted vaccine and commercial vaccine (P<0.05). Significant protection against challenge was merely induced by the oil adjuvanted vaccines (P<0.05). The majority of the studied chickens showed inflammation at the injection site (yellow) throughout the trial. Vaccines made by Montanide ISA 70 and Montanide ISA 71 are novel and effective inactivated vaccines that are able to cause significant protection to fowl cholera disease.
Topics: Animals; Bacterial Vaccines; Chickens; Female; Iran; Mineral Oil; Pasteurella multocida
PubMed: 35096310
DOI: 10.22092/ari.2020.343103.1495 -
Clinical Cancer Research : An Official... Jul 2022Although chemotherapy is standard of care for metastatic colorectal cancer (mCRC), immunotherapy has no role in microsatellite stable (MSS) mCRC, a "cold" tumor....
PURPOSE
Although chemotherapy is standard of care for metastatic colorectal cancer (mCRC), immunotherapy has no role in microsatellite stable (MSS) mCRC, a "cold" tumor. PolyPEPI1018 is an off-the-shelf, multi-peptide vaccine derived from 7 tumor-associated antigens (TAA) frequently expressed in mCRC. This study assessed PolyPEPI1018 combined with first-line maintenance therapy in patients with MSS mCRC.
PATIENTS AND METHODS
Eleven patients with MSS mCRC received PolyPEPI1018 and Montanide ISA51VG adjuvant subcutaneously, combined with fluoropyrimidine/biologic following first-line induction with chemotherapy and a biologic (NCT03391232). In Part A of the study, 5 patients received a single dose; in Part B, 6 patients received up to three doses of PolyPEPI1018 every 12 weeks. The primary objective was safety; secondary objectives were preliminary efficacy, immunogenicity at peripheral and tumor level, and immune correlates.
RESULTS
PolyPEPI1018 vaccination was safe and well tolerated. No vaccine-related serious adverse event occurred. Eighty percent of patients had CD8+ T-cell responses against ≥3 TAAs. Increased density of tumor-infiltrating lymphocytes were detected post-treatment for 3 of 4 patients' liver biopsies, combined with increased expression of immune-related gene signatures. Three patients had objective response according to RECISTv1.1, and 2 patients qualified for curative surgery. Longer median progression-free survival for patients receiving multiple doses compared with a single dose (12.5 vs. 4.6 months; P = 0.017) suggested a dose-efficacy correlation. The host HLA genotype predicted multi-antigen-specific T-cell responses (P = 0.01) indicative of clinical outcome.
CONCLUSIONS
PolyPEPI1018 added to maintenance chemotherapy for patients with unresectable, MSS mCRC was safe and associated with specific immune responses and antitumor activity warranting further confirmation in a randomized, controlled setting.
Topics: Antineoplastic Combined Chemotherapy Protocols; Biological Products; Colonic Neoplasms; Colorectal Neoplasms; Humans; Mineral Oil; Rectal Neoplasms; Vaccines, Subunit
PubMed: 35472243
DOI: 10.1158/1078-0432.CCR-22-0112