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AIM: To investigate the efficacy of fat grafting in primary tendon healing through immunohistochemical and biomechanical examinations. MATERIAL AND METHOD: The study material comprised a total of 10 male Sprague-Dawley rats, each approximately 10 weeks old. All 10 rats were operated on bilaterally. The right Achilles tendon in all the animals was defined as the study group. The tendon was cut and then repaired, and then fat graft was applied to the repair area. The left Achilles tendon of all the rats constituted the control group. The tendon was cut and repaired with no further application. After 4 weeks, the rats were euthanised and samples were taken from the tendons for immunohistochemical and biomechanical examinations. RESULTS: In the biomechanical evaluations, no statistically significant difference was determined between the groups in respect of peak load and stiffness values (p: .068, p: .089, respectively). In the histopathological evaluation, the tenocyte value of the study group was superior to that of the control group (p: .04). No statistically significant differences were determined between the groups in respect of the other histopathological parameters. In the immunohistochemical evaluations, the type I collagen and TGF values of the study group were found to be higher than those of the control group (p: .011, p: .012, respectively). CONCLUSION: Compared to stem cell applications, the use of fat grafting is clinically easy to apply, has low costs, and has been shown to contribute to tendon healing at an immunohistochemical level with increased collagen and TGF beta values.
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Tendón Calcáneo , Cicatrización de Heridas , Ratas , Masculino , Animales , Ratas Sprague-Dawley , Fenómenos Biomecánicos , Colágeno/farmacología , Tendón Calcáneo/cirugía , Tendón Calcáneo/patologíaRESUMEN
Background: There have been many testicular losses due to testicular compartment syndrome (TCS). Studies are ongoing to lower the pressure within tunica vaginalis during TCS. Aims: To provide enough space for reperfusion of the testicular tissue and to reduce intratesticular pressure by resecting testicular tissue in the affected testis for treatment of TCS. Materials and Methods: The study was designed as a prospective randomized animal study. A total of 24 Wistar albino adult rats were randomly divided into three groups. After torsion surgery group 1 underwent detorsion + testicular tissue resection (TTR), while only detorsion was performed in group 2. The control group did not undergo any procedures. At the postoperative 5th day all subjects were sacrificed, and their testes were evaluated in terms of histologic findings, apoptosis, and microangiogenesis. One-way ANOVA and Tukey's test were used for analysis. Results: According to Johnsen scores, all the groups were statistically different from each other and the damage in group 1 was less than in group 2 (P < 0.05). Factor VIII expressions in surgical groups were significantly higher than in the control group (P < 0.05). However, the surgical groups did not show any significant difference between each other (P > 0.05). Apoptotic cell counts were higher in both surgical groups than in the control group. Also, there was significantly higher apoptotic cell count in group 2 than in group 1 (P < 0.05). Conclusions: The injury secondary to TCS is lower when TTR is performed. In the cases in which tunica vaginalis graft could not be obtained or in the delayed cases, TTR may be useful.
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Torsión del Cordón Espermático , Testículo , Humanos , Ratas , Masculino , Animales , Testículo/cirugía , Torsión del Cordón Espermático/cirugía , Estudios Prospectivos , Ratas Wistar , ApoptosisRESUMEN
Introduction Cocaine use during pregnancy can affect fetal brain development. A fetal brain injury could happen from the direct effect of cocaine on the developing brain or from the reduction of placental perfusion from vasoconstriction, which may lead to hypoxia-ischemia. A potential mechanism for brain injury could be due to a neurotransmitter imbalance within the brain, especially glutamate. In an immature rat brain synaptosome model, we explored the additive effect of cocaine alone on glutamate release and the effect of cocaine combined with simulated hypoxic depolarization using potassium as a surrogate. Method Rat pups' brains were dissected and placed on a chilled petri dish. They then entered the experimental protocol. The suspended synaptosomes were divided equally into four experimental groups (control, high potassium "surrogate to hypoxic stimulation," cocaine, and cocaine + high K). Reversed-phase high-performance liquid chromatography analyzed glutamate with fluorescent detection Results The glutamate level was lowest in the cocaine-only group, with a level of 1.96 × 104, compared to the control and high potassium group. However, combining cocaine with high potassium seemed to generate a synergistic effect, achieving the highest glutamate level of all groups with a value of 5.31 × 104. Post hoc Conover's test for multiple pairwise-comparison between groups was done. In comparing various solutions to control, we did not find a statistically significant difference with the cocaine-only solution with a p-value of 0.074. Also, on comparing various other solutions to each other, there was no statistically significant difference between cocaine vs. cocaine + high potassium a p-value of 0.074. Conclusion Our data support the conclusion that cocaine alone does not induce glutamate release from fetal rat brain synaptosomes. Exposure to high potassium does lead to glutamate release. However, cocaine greatly enhances glutamate release in the presence of high potassium levels. This could explain how cocaine affects brain maturation during pregnancy with a low oxygen tension environment in the placenta. This hypothesis should be tested in vivo.
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Bile solubilization plays a major role in the absorption of poorly water-soluble drugs. Excipients used in oral drug formulations impact bile-colloidal properties and their molecular interactions. Polymer-induced changes of bile colloids, e.g., by Eudragit E, reduced the flux of the bile interacting drug Perphenazine whereas bile non-interacting Metoprolol was not impacted. This study corroborates these in vitro findings in rats. Eudragit E significantly reduced systemic availability of Perphenazine but not Metoprolol compared to the oral administrations without polymer. This study confirms the necessity to carefully select polymers for bile interacting drugs whereas non-bile interacting drugs are more robust in terms of excipient choice for formulation. The perspective of bile interaction may introduce interesting biopharmaceutical leverage for better performing oral formulations of tomorrow.
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Excipientes , Perfenazina , Animales , Preparaciones Farmacéuticas , Polímeros , Ratas , SolubilidadRESUMEN
OBJECTIVES: The aim of the study was to evaluate the negative effect of nonionizing radiation on the treatment of endometrial hyperplasia (EH) with oral progesterone. DESIGN: Forty oophorectomized Wistar Albino female rats were included in this experimental rat study. MATERIALS AND METHODS: The 4 groups were planned as follows: Group A; sham group; Group B; group receiving oral estradiol hemihydrate 4 mg/kg/day; Group C; 4 mg/kg/day oral estradiol hemihydrate followed with 1 mg/day medroxy progesterone acetate (MPA) and Group D; 4 mg/kg/day oral estradiol hemihydrate followed with 1 mg/day MPA with exposure to nonionizing radiation at 1800 mHz/3 h/day. After the experimental model, uterine horns were sampled and the preparations were evaluated for pathological parameters (glandular density, epithelial cell length, and luminal epithelial cell length) via light microscopy. Nonionizing radiation was created by a signal generator and a compatible mobile phone. RESULTS: Estrogen was found to increase all parameters related to EH (p < 0.05). Progesterone treatment was found to decrease parameters related to EH (Group B vs. C; luminal epithelial cell length, glandular density, and epithelial length; 11.2 vs. 13.2 µm p = 0.007; 32.5 vs. 35.5, p = 0.068; and 219.9 µm vs. 285 µm, p < 0.001, respectively). Final analyses revealed reduced effectiveness of progesterone treatment in the rats exposed to nonionizing radiation (Group C vs. D); luminal epithelial cell length, glandular density, and epithelial length (11.2 µm vs. 13.5 µm, p = 0.179; 32.5 vs. 52, p < 0.001; and 219.9 µm vs. 374.1 µm, p = 0.001, respectively). LIMITATIONS: The limitations of our study are that the results of animal experiments may not be appropriate for direct adaptation to humans and the relatively low number of rats included in the study. CONCLUSION: Nonionizing radiation reduces the effect of progesterone in patients receiving treatment for EH.
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Hiperplasia Endometrial , Animales , Hiperplasia Endometrial/tratamiento farmacológico , Endometrio , Estradiol , Femenino , Humanos , Progesterona , Radiación no Ionizante , Ratas , Ratas WistarRESUMEN
The current study evaluated the γ-aminobutyric acid (GABA) producing ability from three novel strains of lactic acid bacteria (L. plantarum Taj-Apis362, assigned as UPMC90, UPMC91, and UPMC1065) co-cultured with starter culture in a yogurt. A combination of UPMC90 + UPMC91 with starter culture symbiotically revealed the most prominent GABA-producing effect. Response surface methodology revealed the optimized fermentation conditions at 39.0 °C, 7.25 h, and 11.5 mM glutamate substrate concentration to produce GABA-rich yogurt (29.96 mg/100 g) with desirable pH (3.93) and water-holding capacity (63.06%). At 2% glucose to replace pyridoxal-5-phosphate (PLP), a cofactor typically needed during GABA production, GABA content was further enhanced to 59.00 mg/100 g. In vivo study using this sample revealed a blood pressure-lowering efficacy at 0.1 mg/kg GABA dosage (equivalent to 30 mg/kg GABA-rich yogurt) in spontaneously hypertensive rats. An improved method to produce GABA-rich yogurt has been established, involving shorter fermentation time and lower glutamate concentration than previous work, along with glucose induction that omits the use of costly PLP, fostering the potential of developing a GABA-rich functional dairy product through natural fermentation with desirable product quality and antihypertensive property.
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The aim of this rat study was to investigate the effect of liquid intake on the oral bioavailability of an amorphous solid dispersion (ASD) containing the poorly water-soluble compound ABT-869. To this end, an ASD was prepared by hot-melt extrusion and administered in form of powder in an open gelatin capsule. The study consisted of three arms: (1) administration of the ASD without any liquid, (2) administration of the ASD with 1.5 mL of water, and (3) administration of a suspension of crystalline drug in water. Administration of the ASD without water resulted in a 4-fold higher exposure as compared to the suspension of crystalline drug. When administered together with water, the in vivo performance of the ASD was dramatically affected and not superior to that of the suspension of crystalline drug. The observed phenomena could not be explained mechanistically, but may be related to the following effects: (I) a faster dissolution in a larger volume of fluid and subsequent precipitation, (II) a change in gastrointestinal transit time that caused a mismatch between dissolution rate and absorption rate, and/or (III) a difference in the mucosal adherence/distribution pattern caused by the gelatin capsule. It remains to be investigated whether the phenomena observed in this study are exceptionally pronounced or even unique for this particular formulation. Yet, our findings emphasize that the amount of liquid co-administered with oral enabling formulations can have an impact on the bioavailability. The administration regime used in animal studies should therefore be considered carefully.
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Agua/metabolismo , Animales , Disponibilidad Biológica , Cristalización , Portadores de Fármacos/metabolismo , Composición de Medicamentos/métodos , Tránsito Gastrointestinal/fisiología , Masculino , Polvos/metabolismo , Ratas , Ratas Sprague-Dawley , SolubilidadRESUMEN
We evaluated the acute (single-dose) and subacute (repeated-dose) oral toxicity of alcalase-hydrolyzed whey protein concentrate. Our acute study revealed no death or treatment-related complications, and the median lethal dose of whey protein concentrate hydrolysate was >2,500 mg/kg. In the subacute study, when the hydrolysate was fed at 3 different concentrations (200, 400, and 800 mg/kg), no groups showed toxicity changes compared with controls. Then, whey protein concentrate hydrolysate was orally administered to spontaneously hypertensive rats. Results revealed significant reductions in blood pressure in a dose-dependent manner, and dosing at 400 mg/kg led to significant blood pressure reduction (-47.8 mm Hg) compared with controls (blood pressure maintained) and the findings of previous work (-21 mm Hg). Eight peptides-RHPEYAVSVLLR, GGAPPAGRL, GPPLPRL, ELKPTPEGDL, VLSELPEP, DAQSAPLRVY, RDMPIQAF, and LEQVLPRD-were sequentially identified and characterized. Of the peptides, VLSELPEP and LEQVLPRD showed the most prominent in vitro angiotensin-I converting enzyme inhibition with half-maximal inhibitory concentrations of 0.049 and 0.043 mM, respectively. These findings establish strong evidence for the in vitro and in vivo potential of whey protein concentrate hydrolysate to act as a safe, natural functional food ingredient that exerts antihypertensive activity.
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Antihipertensivos/farmacología , Presión Sanguínea/efectos de los fármacos , Proteína de Suero de Leche/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/química , Animales , Antihipertensivos/química , Antihipertensivos/toxicidad , Femenino , Hidrólisis , Masculino , Péptidos/farmacología , Hidrolisados de Proteína/química , Hidrolisados de Proteína/farmacología , Hidrolisados de Proteína/toxicidad , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Subtilisinas/metabolismo , Proteína de Suero de Leche/química , Proteína de Suero de Leche/toxicidadRESUMEN
BACKGROUND: Mannitol has been used intravenously for decreasing cerebral edema since decades. The study was performed to evaluate the effect of its irrigation on edema in live rats. Edema was induced by artificial brain injury. We hereby present our results on the same using live rats and confirm its beneficial effect on reducing edema when used as irrigation. AIMS: The aim of this study is to evaluate the effect of mannitol irrigation in reducing cerebral edema in rat brain after induction of artificial trauma and to compare the results with standard normal saline irrigation using randomized controlled study. SETTINGS AND DESIGN: This study was a prospective randomized controlled trial. MATERIALS AND METHODS: A total of 20 fully grown Albino Wistar rats were subjected to artificial trauma after a burr hole and divided randomly into two groups of ten rats each. One group was subjected to mannitol irrigation after durotomy and the other was subjected to normal saline. Tissue biopsy was sent at the end of 1 h to check for the status of edema and was classified into three grades. STATISTICAL ANALYSIS USED: Comparison of proportions test. RESULTS: Mannitol irrigation produced a statistically significant difference (P = 0.022) in the grade of edema at the end of 1 h as compared to normal saline. CONCLUSIONS: Mannitol irrigation can be used during neurosurgical procedures instead of normal saline to reduce postoperative brain edema.
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Lentil, a moderate-energy high-protein pulse crop, provides significant amounts of essential nutrients for healthy living. The objective of this study was to determine if a lentil-based diet affects food and energy intake, body weight, percent body fat, liver weight, and body plasma triacylglycerols (TGs) as well as the composition of fecal microbiota in rats. A total of 36 Sprague-Dawley rats were treated with either a standard diet, a 3.5% high amylose corn starch diet, or a 70.8% red lentil diet for 6 weeks. By week 6, rats fed the lentil diet had significantly lower mean body weight (443 ± 47 g/rat) than those fed the control (511 ± 51 g/rat) or corn (502 ± 38 g/rat) diets. Further, mean percent body fat and TG concentration were lower, and lean body mass was higher in rats fed the lentil diet than those fed the corn diet. Fecal abundance of Actinobacteria and Bacteriodetes were greater in rats fed the lentil or corn starch diets than those fed the control diet. Fecal abundance of Firmicutes, a bacterial phylum comprising multiple pathogenic species, decreased in rats fed the lentil and high-amylose corn starch diets vs the control diet. The lentil-based diet decreased body weight, percent body fat, and plasma triacylglycerols in rats and suppressed intestinal colonization by pathogens.
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Microbioma Gastrointestinal , Lens (Planta)/metabolismo , Obesidad/tratamiento farmacológico , Animales , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Bacterias/metabolismo , Biomarcadores/análisis , Ingestión de Energía , Heces/microbiología , Humanos , Lens (Planta)/química , Masculino , Obesidad/metabolismo , Obesidad/microbiología , Ratas , Ratas Sprague-Dawley , Semillas/química , Semillas/metabolismo , Triglicéridos/metabolismoRESUMEN
INTRODUCTION: Locally delivered, crystalline vancomycin has been suggested as a potential prophylactic measure against the development of deep and superficial surgical site infection. Clinical expectations regarding the duration and peak of drug concentration in local tissues following administration are unknown. Our goal was to develop concentration vs time curves for locally administered vancomycin powder in a high-energy, open femur fracture rat model in local tissues and to compare that data to two well performed similar, systemic administration studies. METHODS: After approval for animal research, 24 adult Sprague-Dawley rats sustained closed, midshaft femoral fracture under anesthesia. Fractures were caused via blunt guillotine with 750g metal rod dropped 50cm. Injured hindlimbs were surgically opened at fracture to simulate open injury and stabilized using 0.054 Kirschner wires. Vancomycin powder was administered using weight-based protocol (goal: 25mg/kg). Rats were sacrificed in groups of 4 at 4, 8, 24, 48, 72, 96h. Samples harvested included rat-tail venous blood prior to sacrifice, and femoral bone and anterior thigh soft-tissue were harvested post-mortem. High Performance Liquid Chromatography (HPLC) was performed on all samples. RESULTS: Concentration vs. time curves demonstrated that the surrounding soft-tissues demonstrated highest maximum concentration (1.5mg vancomycin/g muscle). Bone reached maximum average of 199µg vancomycin/g femur: approximately 13% of maximal soft-tissue absorption. Plasma reached maximum concentration of 1.8µg/mL plasma. All peaks at t=4h. Within 48h, average muscle vancomycin concentration dropped to 3µg/g muscle (0.2% maximum muscle concentration) and the average bone concentration dropped to 1.9µg/g femur (0.9% maximum bone concentration). Vancomycin was undetectable on all samples at 96h. Comparison to classical animal studies suggest local delivery to bone exceeds that of IV dosing for approximately 48h and may peak near concentrations of 102 multiples. CONCLUSIONS: Locally administered vancomycin provides drug delivery in excess of IV dosing for approximately 48h after intervention. Exponential decay demonstrates rapid removal of drug to near undetectable levels in bone, plasma, and local soft tissue thereafter in a rat model. Local delivery may generate concentrations exceeding that achievable by steady state systemic dosing for 48h.
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Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Modelos Animales de Enfermedad , Fracturas del Fémur/metabolismo , Fémur/metabolismo , Vancomicina/administración & dosificación , Vancomicina/farmacocinética , Animales , Antibacterianos/farmacología , Desbridamiento , Fracturas del Fémur/tratamiento farmacológico , Fracturas del Fémur/microbiología , Fémur/efectos de los fármacos , Fracturas Abiertas/tratamiento farmacológico , Fracturas Abiertas/metabolismo , Fracturas Abiertas/microbiología , Polvos , Ratas , Ratas Sprague-Dawley , Infecciones Estafilocócicas/prevención & control , Infección de la Herida Quirúrgica/prevención & control , Vancomicina/farmacologíaRESUMEN
Traditional Chinese medicines (TCM) are increasingly being used as alternative medicines in many countries, and this has caused concern because of adverse health effects from toxic metal bioavailability such as mercury (Hg) and arsenic (As). The aim of this study was to investigate the bioavailability of As and Hg from TCM after a single exposure dose using an animal model of female Sprague-Dawley rats. The rats were divided into 6 groups which included four groups treated with sodium arsenite (NaAsO2), arsenic sulfide (As2S3), mercuric chloride (HgCl2), mercuric sulfide (HgS), and two groups treated with TCM containing high Hg or As (Liu Shen Wan: As 7.7-9.1% and Hg 1.4-5.0%; Niuhang Jie du Pian: As 6.2-7.9% and Hg <0.001%). The samples of urine, faeces, kidney and liver were collected for analysis and histological assay. The results indicated that relatively low levels of As and Hg from these TCM were retained in liver and kidney tissues. The levels of As in these tissues after TCM treatment were consistent with the levels from the As sulphide treated group. With the exception of the mercuric chloride treated group, the levels of Hg in urine from other groups were very low, and high levels of As and Hg from TCM were excreted in faeces. The study showed poor bioavailability of As and Hg from TCM as indicated by low relative bioavailability of As (0.60-1.10%) and Hg (<0.001%). Histopathological examination of rat kidney and liver tissues did not show toxic effects from TCM.
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Arsenicales/farmacocinética , Arsenitos/farmacocinética , Contaminación de Medicamentos , Medicamentos Herbarios Chinos/farmacocinética , Cloruro de Mercurio/farmacocinética , Compuestos de Mercurio/farmacocinética , Compuestos de Sodio/farmacocinética , Sulfuros/farmacocinética , Administración Oral , Animales , Arsenicales/administración & dosificación , Arsenicales/orina , Arsenitos/administración & dosificación , Arsenitos/toxicidad , Arsenitos/orina , Disponibilidad Biológica , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/toxicidad , Heces/química , Femenino , Riñón/efectos de los fármacos , Riñón/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Cloruro de Mercurio/administración & dosificación , Cloruro de Mercurio/toxicidad , Cloruro de Mercurio/orina , Compuestos de Mercurio/administración & dosificación , Compuestos de Mercurio/toxicidad , Compuestos de Mercurio/orina , Ratas Sprague-Dawley , Medición de Riesgo , Compuestos de Sodio/administración & dosificación , Compuestos de Sodio/toxicidad , Compuestos de Sodio/orina , Sulfuros/administración & dosificación , Sulfuros/toxicidad , Sulfuros/orina , Distribución TisularRESUMEN
The advancement of technology and the growth of international commerce underscore the need for global harmonization of regulatory safety requirements and their assessment pertaining to consumer products such as drugs, medical devices, and food. This need is particularly relevant when safety requirements involve time-intensive and costly animal safety studies. Here we present the current regulatory requirements in Europe, the United States, and Japan for flavoring substances (FSs) used in foods and point out significant differences relevant to the international standardization for safety assessments that in our opinion need to be addressed and overcome. The safety assessments that are carried out for FSs in various countries are influenced by divergent definitions of FS, by the information required and available for regulatory submission, and by different regulatory procedures, including the use of decision tree approaches. The European Food Safety Authority (EFSA), the Expert Panel of the U.S. Flavor and Extract Manufacturers Association (FEMA), and the Joint Food and Agriculture Organization (FAO)/World Health Organization (WHO) Expert Committee on Food Additives (JECFA) are making efforts to improve and harmonize the safety assessment of FSs. The application of in silico methods such as quantitative structure-activity relationships and read-across strategies relying on expert input are useful as a first-step screening of the assessment. Application of the Threshold of Toxicological Concern (TTC) approach permits conclusions that are compatible with the risk assessment approaches currently used by international advisory committees. The Japanese Regulatory Authority, on the other hand, does not yet consider in silico methods but still requires in vivo and in vitro genotoxicity test data as well as repeat-dose 90-day toxicity data in at least one species, to be submitted as the first step in the safety assessment of FSs. With this article, we echo requests that have been made for xenobiotics by the pharmaceutical industry worldwide, extending them to food-related products, especially FSs. We encourage regulatory agencies to adopt globally harmonized safety assessment procedures, regulatory guidelines, and review practices for FSs to foster global trade and to reduce costs and laboratory animal use.
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Aromatizantes/toxicidad , Medición de Riesgo/métodos , Medición de Riesgo/normas , Pruebas de Toxicidad/métodos , Pruebas de Toxicidad/normas , Animales , Simulación por Computador , Árboles de Decisión , Europa (Continente) , Humanos , Cooperación Internacional , Japón , Ratas , Organización Mundial de la SaludRESUMEN
BACKGROUND AND OBJECTIVES: A fiberoptic microneedle device (FMD) was designed and fabricated for the purpose of enhancing the volumetric dispersal of macromolecules delivered to the brain through convection-enhanced delivery (CED) by concurrent delivery of sub-lethal photothermal hyperthermia. This study's objective was to demonstrate enhanced dispersal of fluid tracer molecules through co-delivery of 1,064 nm laser energy in an in vivo rodent model. MATERIALS AND METHODS: FMDs capable of co-delivering fluids and laser energy through a single light-guiding capillary tube were fabricated. FMDs were stereotactically inserted symmetrically into both cerebral hemispheres of 16 anesthetized rats to a depth of 1.5 mm. Laser irradiation (1,064 nm) at 0 (control), 100, and 200 mW was administered concurrently with CED infusions of liposomal rhodamine (LR) or gadolinium-Evans blue-serum albumin conjugated complex (Gd-EBA) at a flow rate of 0.1 µl/min for 1 hour. Line pressures were monitored during the infusions. Rodents were sacrificed immediately following infusion and their brains were harvested, frozen, and serially cryosectioned for histopathologic and volumetric analyses. RESULTS: Analysis by ANOVA methods demonstrated that co-delivery enhanced volumetric dispersal significantly, with measured volumes of 15.8 ± 0.6 mm(3) for 100 mW compared to 10.0 ± 0.4 mm(3) for its fluid only control and 18.0 ± 0.3 mm(3) for 200 mW compared to 10.3 ± 0.7 mm(3) for its fluid only control. Brains treated with 200 mW co-delivery exhibited thermal lesions, while 100 mW co-deliveries were associated with preservation of brain cytoarchitecture. CONCLUSION: Both lethal and sub-lethal photothermal hyperthermia substantially increase the rate of volumetric dispersal in a 1 hour CED infusion. This suggests that the FMD co-delivery method could reduce infusion times and the number of catheter insertions into the brain during CED procedures.