Kinetics of Infection-Driven Growth Model with Birth and Death

We propose a two-species infection model, in which an infected aggregate can gain one monomer from a healthy one due to infection when they meet together. Moreover, both the healthy and infected aggregates may lose one monomer because of self-death, but a healthy aggregate can spontaneously yield a new monomer. Consider a simple system in which the birth/death rates are directly proportional to the aggregate size, namely, the birth and death rates of the healthy aggregate of size k are J₁k and J₂k while the self-death rate of the infected aggregate of size k is J₃k. We then investigate the kinetics of such a system by means of rate equation approach. For the J₁>J₂ case, the aggregate size distribution of either species approaches the generalized scaling form and the typical size of either species increases wavily at large times. For the J₁=J₂ case, the size distribution of healthy aggregates approaches the generalized scaling form while that of infected aggregates satisfies the modified scaling form. For the J₁<J₂ case, the size distribution of healthy aggregates satisfies the modified scaling form, but that of infected aggregates does not scale.     

Topical Nano Clove/Thyme Gel against Genetically Identified Clinical Skin Isolates: In Vivo Targeting Behavioral Alteration and IGF-1/pFOXO-1/PPAR γ Cues

Antimicrobial resistance is a dramatic global threat; however, the slow progress of new antibiotic development has impeded the identification of viable alternative strategies. Natural antioxidant-based antibacterial approaches may provide potent therapeutic abilities to effectively block resistance microbes’ pathways. While essential oils (EOs) have been reported as antimicrobial agents, its application is still limited ascribed to its low solubility and stability characters; additionally, the related biomolecular mechanisms are not fully understood. Hence, the study aimed to develop a nano-gel natural preparation with multiple molecular mechanisms that could combat bacterial resistance in an acne vulgaris model. A nano-emulgel of thyme/clove EOs (NEG8) was designed, standardized, and its antimicrobial activity was screened in vitro and in vivo against genetically identified skin bacterial clinical isolates (Pseudomonas stutzeri, Enterococcus faecium and Bacillus thuringiensis). As per our findings, NEG8 exhibited bacteriostatic and potent biofilm inhibition activities. An in vivo model was also established using the commercially available therapeutic, adapalene in contra genetically identified microorganism. Improvement in rat behavior was reported for the first time and NEG8 abated the dermal contents/protein expression of IGF-1, TGF-β/collagen, Wnt/β-catenin, JAK2/STAT-3, NE, 5-HT, and the inflammatory markers; p(Ser536) NF-κBp65, TLR-2, and IL-6. Moreover, the level of dopamine, protective anti-inflammatory cytokine, IL-10 and PPAR-γ protein were enhanced, also the skin histological structures were improved. Thus, NEG8 could be a future potential topical clinical alternate to synthetic agents, with dual merit mechanism as bacteriostatic antibiotic action and non-antibiotic microbial pathway inhibitor.     

The effect of frequency and power density on the ultrasonically-enhanced killing of biofilm-sequestered Escherichia coli

Infection on implanted medical devices is a critical concern because the bacteria are recalcitrant to antibiotic therapy; currently the only way to eliminate the infection is to remove the device. We have found that low-frequency ultrasound renders bacteria more susceptible to antibiotics. The effect of low-intensity ultrasound on the enhancement of antibiotic action against biofilm bacteria was measured by subjecting thick E. coli biofilms for 2 h at 37°C to one of four conditions: (1) incubation in nutrient broth; (2) incubation in nutrient broth with antibiotic; (3) ultrasonication in nutrient broth without antibiotic; and (4) ultrasonication in nutrient broth with antibiotic. Two frequencies (70 and 500 kHz) and several ultrasonic intensities were examined, ranging from 2 to 200 mW/cm². It was determined that low-intensity ultrasound significantly enhanced killing of biofilm E. coli by gentamicin. This enhancement increased with increasing ultrasonic intensity and decreased with increasing frequency. A mathematical model of ultrasonically-enhanced transport in cylindrical pores and channels shows that gentamicin transport increases with ultrasonic intensity and decreases with increasing frequency. However, the magnitude of increased transport is so small that it is difficult to attribute enhanced killing of bacteria to enhanced antibiotic transport through the pores and channels of the biofilm; therefore, other mechanisms must play a role. The use of low-intensity ultrasound in conjunction with antibiotic treatment may prove to be a viable clinical method of eliminating biofilm infections from the surfaces of implanted medical devices.     

Quantitative determination of saquinavir from Caco-2 cell monolayers by HPLC-UV. High performance liquid chromatography

The validation and quantitative determination of the protease inhibitor, saquinavir, from confluent Caco-2 monolayers and from aqueous solution is reported. The high performance liquid chromatographic method consisted of an Ultramex 5 C(8) reverse-phase column (250 x 4.6 mm i.d.) and a mobile phase of acetonitrile:water:triethylamine (55:44:1, v/v/v, pH 6.5). Samples were analyzed using an ultraviolet detector at 238 nm, and diltiazem hydrochloride (66 micro g/mL) was used as an internal standard. A linear response over a broad concentration range (0.4-8.0 micro g/mL, r(2) = 0.997) was obtained. The limit of detection and quantitation was set at 0.14 and 0.4 micro g/mL, respectively. Over a 4 day period, the intra-day and inter-day precision ranged from 1 to 7% with a mean of 4%, and from 1 to 2% with a mean of 1.5%, respectively. Bench-top and storage stability of saquinavir was found to be satisfactory. The permeability of saquinavir through Caco-2 monolayers was estimated using this assay.     

Osteomyelitis: Sensitivity of 0.064 T MRI, three-phase bone scanning and indium scanning with biopsy proof

We compared the ability of magnetic resonance imaging (MRI) using a 0.064 T permanent magnet, three-phase bone scanning, and indium-labeled white blood cell (¹¹¹In-WBC) scanning, to diagnose osteomyelitis. Twenty-three patients underwent biopsy. All patients were examined at presentation with all three modalities. Sensitivities for each modality were calculated using biopsy as a gold standard. The results were 72% for MRI, 68% for bone scan, and 45% for ¹¹¹In-WBC. Specificities were not calculated because of lack of negative biopsies. MRI was as sensitive as bone scanning in the diagnosis of osteomyelitis. All modalities had lower than previously reported sensitivities for imaging osteomyelitis.     

Fabrication and Evaluation of Voriconazole Loaded Transethosomal Gel for Enhanced Antifungal and Antileishmanial Activity

Voriconazole (VRC) is a broad-spectrum antifungal agent belonging to BCS class II (biopharmaceutical classification system). Despite many efforts to enhance its solubility, this primary issue still remains challenging for formulation scientists. Transethosomes (TELs) are one of the potential innovative nano-carriers for improving the solubility and permeation of poorly soluble and permeable drugs. We herein report voriconazole-loaded transethosomes (VRCT) fabricated by the cold method and followed by their incorporation into carbopol 940 as a gel. The prepared VRCT were evaluated for % yield, % entrapment efficiency (EE), surface morphology, possible chemical interaction, particle size, zeta potential, and polydispersity index (PDI). The optimized formulation had a particle size of 228.2 nm, a zeta potential of −26.5 mV, and a PDI of 0.45 with enhanced % EE. Rheology, spreadability, extrudability, in vitro release, skin permeation, molecular docking, antifungal, and antileishmanial activity were also assessed for VRCT and VRC loaded transethosomal gel (VTEG). Ex-vivo permeation using rat skin depicted a transdermal flux of 22.8 µg/cm²/h with enhanced efficiency up to 4-fold. A two-fold reduction in inhibitory as well as fungicidal concentration was observed against various fungal strains by VRCT and VTEG besides similar results against L-donovani. The development of transethosomal formulation can serve as an efficient drug delivery system through a topical route with enhanced efficacy and better patient compliance.     

K-means聚类算法在SIR传染病模型中的应用研究

基于SIR传染病模型,建立了具有K-means聚类算法的SIR元胞自动机模拟模型.通过对分别服从高斯分布和随机均匀分布的两类初始感染源的分析与模拟,给出了疾病感染半径与隔离半径对疾病传播的影响.结果显示:在两种不同类型的初试分布下,感染者的最大值分别与疾病感染传播半径和隔离半径呈正相关与负相关关系,感染者数量随时间的变...     

硒对呼吸系统感染的防治作用

介绍了硒的免疫作用机制及在呼吸系统感染性疾病防治中的作用。硒是一种重要的人体必需微量元素。适量的硒可增强细胞免疫、体液免疫及非特异免疫功能 ,缺硒会损害免疫系统的功能 ,硒在呼吸系统感染性疾病防治方面亦有诸多报道     

Kinetics of Infection-Driven Growth Model with Birth and Death

We propose a two-species infection model, in which an infected aggregate can gain one monomer from a healthy one due to infection when they meet together. Moreover, both the healthy and infected aggregates may lose one monomer because of self-death, but a healthy aggregate can spontaneously yield a new monomer. Consider a simple system in which the birth/death rates are directly proportional to the aggregate size, namely, the birth and death rates of the healthy aggregate of size k are J1 k and J2k while the self-death rate of the infected aggregate of size k is J3k. We then investigate the kinetics of such a system by means of rate equation approach. For the J1 〉 J2 case, the aggregate size distribution of either species approaches the generalized scaling form and the typical size of either species increases wavily at large times. For the J1 = J2 case, the size distribution of healthy aggregates approaches the generalized scaling form while that of infected aggregates satisfies the modified scaling form. For the J1 〈 J2 case, the size distribution of healthy aggregates satisfies the modified scaling form, but that of infected aggregates does not scale.     

Establishment of the milk-borne transmission as a key factor for the peculiar endemicity of human T-lymphotropic virus type 1 (HTLV-1): the ATL Prevention Program Nagasaki

In late 2010, the nation-wide screening of pregnant women for human T-lymphotropic virus type 1 (HTLV-1) infection was implemented in Japan to prevent milk-borne transmission of HTLV-1. In the late 1970s, recognition of the adult T-cell leukemia (ATL) cluster in Kyushu, Japan, led to the discovery of the first human retrovirus, HTLV-1. In 1980, we started to investigate mother-to-child transmission (MTCT) for explaining the peculiar endemicity of HTLV-1. Retrospective and prospective epidemiological data revealed the MTCT rate at ～20%. Cell-mediated transmission of HTLV-1 without prenatal infection suggested a possibility of milk-borne transmission. Common marmosets were successfully infected by oral inoculation of HTLV-1 harboring cells. A prefecture-wide intervention study to refrain from breast-feeding by carrier mothers, the ATL Prevention Program Nagasaki, was commenced in July 1987. It revealed a marked reduction of HTLV-1 MTCT by complete bottle-feeding from 20.3% to 2.5%, and a significantly higher risk of short-term breast-feeding (<6 months) than bottle-feeding (7.4% vs. 2.5%, P < 0.001).