Spatiotemporal modeling of nano-delivered chemotherapeutics for synergistic microwave ablation cancer therapy.

BACKGROUND AND OBJECTIVE: The effectiveness of current microwave ablation (MWA) therapies is limited. Administration of thermosensitive liposomes (TSLs) which release drugs in response to heat has presented a significant potential for enhancing the efficacy of thermal ablation treatment, and the benefits of targeted drug delivery. However, a complete knowledge of the mechanobiological processes underlying the drug release process, especially the intravascular drug release mechanism and its distribution in response to MWA needs to be improved. Multiscale computational-based modeling frameworks, integrating different biophysical phenomena, have recently emerged as promising tools to decipher the mechanobiological events in combo therapies. The present study aims to develop a novel multiscale computational model of TSLs delivery following MWA implantation. METHODS: Due to the complex interplay between the heating procedure and the drug concentration maps, a computational model is developed to determine the intravascular release of doxorubicin from TSL, its transvascular transport into the interstitium, transport in the interstitium, and cell uptake. Computational models can estimate the interplays among liposome and drug properties, tumor perfusion, and heating regimen to examine the impact of essential parameters and to optimize a targeted drug delivery platform. RESULTS: Results indicated that the synergy of TSLs with MWA allows more localized drug delivery with lower side effects. The drug release rate and tumor permeability play crucial roles in the efficacy of TSLs during MWA treatment. The computational model predicted an unencapsulated drug lime around the ablated zone, which can destroy more cancer cells compared to MWA alone by 40%. Administration of TSLs with a high release rate capacity can improve the percentage of killed cancer cells by 24%. Since the heating duration in MWA is less than 15 min, the presented combination therapy showed better performance for highly permeable tumors. CONCLUSION: This study highlights the potential of the proposed computational framework to address complex and realistic scenarios in cancer treatment, which can serve as the future research foundation, including advancements in nanomedicine and optimizing the pair of TSL and MWA for both preclinical and clinical studies. The present model could be as a valuable tool for patient-specific calibration of essential parameters.

Effect of tumor heterogeneity on enhancing drug delivery to vascularized tumors using thermo-sensitive liposomes triggered by hyperthermia: A multi-scale and multi-physics computational model.

In this study, a novel multi-scale and multi-physics image-based computational model is introduced to assess the delivery of doxorubicin (Dox) loaded temperature-sensitive liposomes (TSLs) in the presence of hyperthermia. Unlike previous methodologies, this approach incorporates capillary network geometry extracted from images, resulting in a more realistic physiological tumor model. This model holds significant promise in advancing personalized medicine by integrating patient-specific tumor properties. The finite element method is employed to solve the equations governing intravascular and interstitial fluid flows, as well as the transport of therapeutic agents within the tissue. Realistic biological conditions and intricate processes like intravascular pressure, drug binding to cells, and cellular uptake are also considered to enhance the model's accuracy. The results underscore the significant impact of vascular architecture on treatment outcomes. Variation in vascular network pattern yielded changes of up to 38 % in the fraction of killed cells (FKCs) parameter under identical conditions. Pressure control of the parent vessels can also improve FKCs by approximately 17 %. Tailoring the treatment plan based on tumor-specific parameters emerged as a critical factor influencing treatment efficacy. For instance, changing the time interval between the administration of Dox-loaded TSLs and hyperthermia can result in a 48 % improvement in treatment outcomes. Additionally, devising a customized heating schedule led to a 20 % increase in treatment efficacy. Our proposed model highlights the significant effect of tumor characteristics and vascular network structure on the final treatment outcomes of the presented combination treatment.

Analysis of Magneto-Hyperthermia Duration in Nano-sized Drug Delivery System to Solid Tumors Using Intravascular-Triggered Thermosensitive-Liposome.

Computational models have been developed as a potential platform to identify bio-interactions that cannot be properly understood by experimental models. In the present study, a mathematical model has been employed to investigate the therapeutic response of drug-loaded thermosensitive liposome (TSL) following intravascular release paradigm. Thermal field created by an alternating magnetic field is utilized to release the drug within microvessels. Determining the time required for the application of magneto-hyperthermia is the main purpose of this study. Results show that applying a long-term continuous or pulsed hyperthermia can affect the concentration level of drugs in the extracellular space. The peak value of free and bound drug concentrations in the extracellular space is equal for all hyperthermia programs. Additionally, the concentrations of free and bound drugs are retained at a higher level in pulsed mode compared to the continuous mode (i.e., area under curve (AUC) of pulsed case is slightly higher than continuous case). However, there is no significant difference in bioavailability time. Hence, onset time of tumor growth is similar for different conditions. This study shows that the appropriate time to apply hyperthermia is post-bolus injection until reaching the peak concentration profile in extracellular space. Therefore, in clinical applications similar to the present study's circumstances, continuous hyperthermia for 30 min can be a better choice. This study can be a useful guideline for experimental studies to reduce the number of in vivo tests as well as for clinical trials to make the right decision to provide optimal medication programs.

Probiotics, lactic acid bacteria and bacilli: interesting supplementation for aquaculture.

Probiotics administration in aquafeed is known to increase feed consumption and absorption due to their capacity to release a wide range of digestive enzymes and nutrients which can participate in digestion process and feed utilization, along with the absorption of diet components led to an increase in host's health and well-being. Furthermore, probiotics improve gut maturation, prevention of intestinal disorders, predigestion of antinutrient factors found in the feed ingredients, gut microbiota, disease resistance against pathogens and metabolism. The beneficial immune effects of probiotics are well established in finfish. However, in comparison, similar studies are less abundant in the shellfish. In this review, the discussions will mainly focus on studies reported the last 2 years. In recent studies, native probiotic bacteria were isolated and fed back to their hosts. Although beneficial effects were demonstrated, some studies showed adverse effects when treated with a high concentration. This adverse effect may be due to the imbalance of the gut microbiota caused by the replenished commensal probiotics. Probiotics revealed greatest effect on the shrimp digestive system particularly in the larval and early post-larval stages, and stimulate the production of endogenous enzymes in shrimp and contribute with improved the enzyme activities in the gut, as well as disease resistance.

Numerical modeling of high-intensity focused ultrasound-mediated intraperitoneal delivery of thermosensitive liposomal doxorubicin for cancer chemotherapy.

Although intraperitoneal chemotherapy (IPC) has been suggested as a promising method for the management of peritoneal dissemination (PD) of ovarian or colorectal cancers, the actual clinical use of this method has been restricted due to such problems as poor drug penetration into the tumor and high side effects. It is, therefore, necessary to develop new strategies to improve the efficacy of this approach. In the present work, a new strategy is proposed based on intraperitoneal (IP) injection of thermosensitive liposomal doxorubicin (TSL-Dox) with triggered release by mild hyperthermia induced by high intensity focused ultrasound (HIFU). A computational model is developed to evaluate the proposed drug delivery system. Results show an order of magnitude increase in drug penetration depth into the tumor compared to the conventional IP delivery. Furthermore, the effects of thermal conditions applied to the tumor, TSL size, tumor vessel permeability, and tumor size are investigated. Results indicate an improved efficiency of the drug delivery by expanding the heated region, yet, it increases the risk of unintentional TSL drug load release in the peritoneal cavity. Results also indicate that smaller TSLs have better treatment outcome. However, there is a significant reduction in treatment efficacy for TSLs with sizes smaller than the vessel wall pore size. Thus, tuning the size of TSL should be based on the tumor microvascular permeability. The simulation results suggest that the TSL-Dox delivery system in smaller tumors is far advantageous than larger ones. Results of our model can be used as guidelines for future preclinical studies.

Comparison of single- and multi-strain probiotics effects on broiler breeder performance, egg production, egg quality and hatchability.

1. This study was conducted to investigate the effect of multi-strain probiotic (containing Lactobacillus acidophilus 2.5 × 107 cfu/g, Lactobacillus casei 2.5 × 107 cfu/g, Bifidobacterium thermophilum 2.5 × 107 cfu/g and Enterococcus faecium 2.5 × 107 cfu/g) and single-strain probiotic (Pediococcus acidilactici 1 × 1010 cfu/g) on broiler breeder performance and gastrointestinal health. 2. A completely randomised trial was conducted using 300 broiler breeder hens (Ross 308) aged 51 weeks old which were randomly allocated to 1 of 5 dietary treatments with 6 replicates per treatment in a 10 week trial. Treatments included (1) the basal diet a negative control, (2) basal diet supplemented with 0.1 g/kg multi-strain probiotic (MS), (3) basal diet supplemented with 0.1 g/kg single-strain probiotic (SS), (4) basal diet supplemented with 0.1 g/kg of both of probiotics (MS+ SS) and (5) positive control basal diet supplemented with 0.5 g/kg oxytetracycline antibiotic (OX). 3. Body weight, egg production, yolk weight, eggshell thickness and weight, Haugh unit, fertility and hatchability were determined. Results showed that dietary treatments had no significant effect on total hen house or total hatching egg production, egg weight, yolk colour index, shell weight, mortality, body weight, fertility, hatchability, oviduct and stroma weight or number of large and small yellow follicles (P > 0.05). None of the jejunum morphological parameters, apparent ileal digestibility of protein and ileal Lactobacillus population were influenced by supplemental probiotics (P > 0.05), although ileum Escherichia coli count was reduced by inclusion of dietary probiotics (P < 0.05). 4. It was concluded that although both probiotic treatments reduced coliforms, they did not improve broiler breeder performance or gastrointestinal tract (GIT) function.

Protective effects of the hydroalcoholic extract of Fumaria parviflora on testicular injury induced by torsion/detorsion in adult rats.

This study was designed to determine the effects of daily oral administration (250 mg/kg) of the hydroalcoholic extract of Fumaria parviflora (FP) for 14 days on the sperm parameters, oxidative stress parameters, serum testosterone levels, expression of Bax and Bcl-2 genes, and apoptosis index of germ cells after testicular torsion-detorsion (ischaemia-reperfusion, IR) injury model in rats. Twenty-eight adult male Wistar rats were divided randomly into four groups of seven each: sham operation, torsion-detorsion (TD), TD plus the hydroalcoholic extract FP (TDFP) and only FP without TD application (FP). Testicular torsion was created by rotating the left testis 720° in a counterclockwise direction; then, after 4 hr, detorsion was performed. The Johnson's score, mean seminiferous tubule diameter (MSTD) and height (thickness) of seminiferous tubule epithelium (HST) were significantly increased in TDFP and FP groups as compared to TD group. The gene expression of Bcl-2, level of serum testosterone hormone and antioxidant parameters-GPx and SOD-were significantly higher in TDFP and FP groups than TD group. The index of apoptosis, the gene expression of Bax and the level of MDA were significantly higher in TD group than TDFP and FP groups. Therefore, F. parviflora could decrease oxidative stress induced by testicular torsion-detorsion.

[Integrated management of mother and child health in the region of Monastir (Tunisia)]. / Piese en charge intégrér de la santé de la mere et de L'Enfant dans la région de Monastir (Tunisie).

The programme of integrated management of child health (IMCI) was established in Tunisia in 2002 in some health districts. This study evaluated the management of children under 5 years of age and their mothers using the IMCI programme in Zeramdine, a town 20 km south-west of Monastir. A cross-sectional study was conducted on a convenience sample of 526 medical records of children under 5 years attending the Zeramdine maternal and child health centre. The study evaluated preventive and curative aspects of child health. The mean age was 21.9 (SD 16.7) months. On the curative side, respiratory diseases were the leading reason for consultation (71.2%) followed by diarrhoea (15.4%). For preventive services, physicians systematically checked the child's immunization status and height and weight on the growth charts, and screened for strabismus and anaemia. The contribution to child health of IMCI is undeniable; it allows comprehensive care of the child, develops staff skills, upgrades the health system and improves family and community practices.

Integrated management of mother and child health in the region of Monastir [Tunisia]

The programme of integrated management of child health [IMCI] was established in Tunisia in 2002 in some health districts. This study evaluated the management of children under 5 years of age and their mothers using the IMCI programme in Zeramdine, a town 20 km south-west of Monastir. A cross-sectional study was conducted on a convenience sample of 526 medical records of children under 5 years attending the Zeramdine maternal and child health centre. The study evaluated preventive and curative aspects of child health. The mean age was 21.9 [SD 16.7] months. On the curative side, respiratory diseases were the leading reason for consultation [71.2%] followed by diarrhoea [15.4%]. For preventive services, physicians systematically checked the child’s immunization status and height and weight on the growth charts, and screened for strabismus and anaemia. The contribution to child health of IMCI is undeniable; it allows comprehensive care of the child, develops staff skills, upgrades the health system and improves family and community practices

Le programme de la prise en charge intégrée de la Santé de la mère et de l'enfant [PCIME] a été implanté en Tunisie en 2002 dans quelques circonscriptions sanitaires. La présente étude a évalué la prise en charge des enfants de moins de 5 ans et de leurs mères à travers le programme PCIME à Zeramdine, ville située à 20 km au sud-ouest de Monastir. Une étude transversale a été réalisée sur un échantillon représentatif de 526 dossiers médicaux d'enfants de moins de cinq ans consultant dans le centre de protection maternelle et infantile de Zeramdine. L'étude a évalué tous les aspects curatifs et préventifs de la prise en charge de la santé de l'enfant.La moyenne d'âge était de 21,9 mois [ET 16,7]. Sur le plan curatif, les maladies respiratoires dominaient les motifs de consultation [71,2 %], suivies de la diarrhée [15,4 %]. Sur le plan préventif, les médecins vérifiaient systématiquement l'état vaccinal et le développement staturo-pondéral de l'enfant, et assuraient le dépistage de l'anémie et du strabisme. L'apport de la PCIME est indéniable; elle permet une prise en charge globale de l'enfant, le développement des compétences des ressources humaines, la mise a niveau du système de santé et l'amélioration des pratiques familiales et communautaires

Effect of tricainemethanesulfonate (MS222), clove oil and electro-anaesthesia on respiratory burst activity in whole blood and serum alternative complement response in rainbow trout (Oncorhynchus mykiss), during the narcosis stage.

There is a little available information on the suppressive effect of anaesthesia on immune response in fish, especially electro-anaesthesia. In the present study, two anaesthetics, MS222 (50 ppm), clove oil (25 ppm), and electro-anaesthesia were tested in rainbow trout (Oncorhynchus mykiss) during the narcosis stage in order to observe their effects on the innate immune system. The results showed that electro-anaesthesia reduces light emission in chemiluminescence assay both 1 and 24 h post anaesthesia. Clove oil and MS222 decreased light emission 24 h post anaesthesia. In addition, clove oil, MS222 and electro-anaesthesia had no effect on alternative complement (ACH50) response. From the perspective of aquaculture practice, these data show that the type of anaesthesia should be taken into account to avoid possible immunosuppression in rainbow trout.

Evaluation of protective efficacy of Spirulina platensis in Balb/C mice with candidiasis.

OBJECTIVE: This study was aimed at evaluating the immunostimulatory effect of Spirulina platensis in prophylaxis of Balb/C mice with systemic candidiasis. MATERIALS AND METHODS: In first experiment, 40 mice were divided into four groups, ten mice per each group, for cytokines assay. Animals received a dose of 800mg/kg of S. platensis for 4days and then were intravenously inoculated with 1×10(6) Candida albicans. Control groups received 0.2mL and 0.1mL normal saline for prophylaxis and inoculation, respectively. Five mice from each group were euthanized after 24hours and 72hours and the serum levels of IFN-γ and TNF-α were measured by Enzyme-linked immunosorbent assay (ELISA) method. In second experiment, two mice groups with systemic candidiasis, 11 mice per each group, were included to evaluate the survival rate. Animals were monitored for 30days and the kidneys, liver, lungs and spleen were analyzed for fungal invasion. RESULTS: The results indicated that the Spirulina-treated mice produced more IFN-g and TNF-α level than their control groups. This infected group showed that the mean survival time (28.86±2.7) was significantly (P<0.05) higher than control group (13.9±3.34). They also exhibited that fungal clearance in selected organs at death time represents significant differences between spleen and liver (P<0.05). CONCLUSION: Prophylaxis with S. platensis had synergistic effect through producing cytokines such as TNF-α and IFN-γ. Our results provide important information for the potential application of S. platensis in the treatment and resistance of Balb/C mice with systemic candidiasis.

[New criteria and quality of health care services in the governorate of Monastir, Tunisia]. / Les nouveaux critères et la qualité des services de soins de santé dans le gouvernorat de Monastir (Tunisie).

In 2005 new quality criteria (7 items) were introduced for services provided to mother and child under the national perinatality programme. We evaluated this new version in a descriptive study conducted among a random sample of 400 parturient women from Monastir governorate. Mean age was 29.3 (SD 5) years and 42% were primipara. Although prenatal care was adequate in terms of number of antenatal visits for 82.5% of women, for only 21% were all 7 quality criteria fulfilled. The rates of caesarean section and premature birth were significantly higher in women who received quality care (P < 0.05). In logistic regression analysis, age and parity were the only factors independently associated with the quality of care. Additional efforts are needed to ensure good maternal and infant quality of care.

Cell cycle analysis and cytotoxic potential of Ruta graveolens against human tumor cell lines.

There are reports on the presence of various compounds exerting different biological activities in Ruta graveolens, a plant of Rutaceae family. The aim of the present study was to evaluate in vitro cytotoxicity of the total extract of R. graveolens against tumor cell lines of different origin. Aerial parts of the plant was extracted with 70% ethanol by sonication method and cytotoxic activity was examined on RAJI, RAMOS, RPMI8866, U937, Jurkat, MDA-MB-453, MCF-7, LNCap-FGC-10, 5637, HeLa, SK-OV-3, A549, Mehr-80 and also peripheral blood mononuclear cells (PBMC) by the use of WST-1 assay. Results were expressed as IC(50) values. R. graveolens extract showed high cytotoxic activity against RAJI and RAMOS, two Burkitt's lymphoma cell lines, with an IC(50) equal to 24.3 microg/ml and 35.2 microg/ml respectively and LNCap-FGC-10, a prostate adenocarcinoma cell line with an IC(50) equal to 27.6 microg/ml as well as Mehr-80, a newly established Large Cell Lung Carcinoma (IC(50)=46.2 microg/ml). No significant anti-proliferative activity was observed on other cell lines including MCF-7, MDA-MB-453, SK-OV-3, HeLa, 5637, JURKAT and RPMI8866. Adverse cytotoxic effect of R. graveolens was investigated against PBMCs and a significantly lower effect of this extract (IC(50)=104 microg/ml) was seen on normal cells compared with RAJI and RAMOS, two haematopoietic cell lines.